{"title": "02 siri child imz schedule 508", "content": "SENT VIA EMAIL  \n \nAdvisory Committee on Immunization Practices    \nCenters for Disease Control and Prevention  \nacip@cdc.gov   \n \nRe:  Supplement to December 5, 2025 Presentation Titled Development of the U.S.  \nChildhood Vaccination Schedule: With a Focus on Suggested Improvements  \n \nTo ACIP:  \n \nPlease find herein additional sources for various slides for the  above -referenced presentation.  As \ndisclosed in that presentation, I am the Manag ing Partner of Siri & Glimstad LLP which has over \n100 professionals who handle civil rights, exemptions, immigration, employment, and injury \nclaims related to vaccin es.  \n \n \nSLIDE 11 : IMPORTANCE OF CLINICAL TRIALS  \n \nThe importance of the clinical trials relied upon to license each recommended childhood vaccine \nin ACIP’s decision making is highlighted by the following chart which reflects the time period \nbetween licensure and ACIP’s recommendation for each vaccine. Note that this chart reflects all \nroutine ly recommended vaccines  as well as any vaccine used as a control to license a routine ly \nrecommended vaccine, and so forth , down the licensure chain.   \n \nVaccine  Year \nLicensed \nfor \nChildren  Year ACIP Recommended \nfor Routine Use in \nChildren [Earlier Non -\nRoutine Use]  Days Between \nLicensure & \nRecommendation  \nDTP (various)  * 19661 * \nM-M-R-II (Merck)  19782 19783          49 days  \nMenomune  19814     [1985]5 [1264]  \n \n1 https://stacks.cdc.gov/view/cdc/633 . \n2 https://icandecide.org/article/measles -mumps -and-rubella -vaccine -mmr/ . \n3 https://stacks.cdc.gov/view/cdc/1643 . \n4 https://www.drugs.com/pro/menomune.html . \n5 https://stacks.cdc.gov/view/cdc/35394 . \n2 \n Recombivax HB \n(Merck)  19866     [1987]7   19918 [331] 1948 days  \nEngerix -B (GSK)  19899     [1990]10  199111 [192]   816 days  \nPedvaxHIB (Merck)  198912                     199013             133 days  \nIpol (Sanofi)  199014     [1994]15   199716 [1691]  2580 days  \nActHIB (Sanofi)  199317                     199318               24 days  \nVarivax (Merck)  199519                     199620                294 days  \nHavrix (GSK)  199521     [1996]22  200623     [674]  4104 days  \nVaqta (Merck)  199624     [1996] 25  200626     [273]  3703  days  \nInfanrix (GSK)  199727                    199728                  73 days  \nPrevnar 7  200029                    200030                   -1 days  \nDaptacel (Sanofi)  200231                    200232                  52 days  \n \n6 https://purplebooksearch.fda.gov/productdetails?query=101066 . \n7 https://www.cdc.gov/mmwr/preview/mmwrhtml/00019181.htm . \n8 https://www.cdc.gov/mmwr/preview/mmwrhtml/00033405.htm . \n9 https://purplebooksearch.fda.gov/productdetails?query=103239 . \n10 https://stacks.cdc.gov/view/cdc/7460 . \n11 https://www.cdc.gov/mmwr/preview/mmwrhtml/00033405.htm . \n12 https://www.cdc.gov/mmwr/preview/mmwrhtml/00001600.htm . \n13 https://www.cdc.gov/mmwr/preview/mmwrhtml/00001600.htm . \n14 https://usa -mama.com/wp -content/uploads/2017/02/us -vaccines.pdf . \n15 https://stacks.cdc.gov/view/cdc/26885 . \n16 https://www.cdc.gov/mmwr/preview/mmwrhtml/00046568.htm . \n17 https://www.cdc.gov/mmwr/preview/mmwrhtml/00020301.htm . \n18 https://www.cdc.gov/mmwr/preview/mmwrhtml/00020301.htm . \n19 https://stacks.cdc.gov/view/cdc/76570/cdc_76570_DS1.pdf . \n20 https://stacks.cdc.gov/view/cdc/76570/cdc_76570_DS1.pdf .  \n21 https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5507a1.htm . \n22 https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5507a1.htm . \n23 https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5507a1.htm . \n24 https://www.cdc.gov/mmwr/preview/mmwrhtml/00048084.htm . \n25 https://www.cdc.gov/mmwr/preview/mmwrhtml/00048084.htm . \n26 https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5507a1.htm . \n27 https://www.cdc.gov/mmwr/PDF/rr/rr4607.pdf . \n28  https://www.cdc.gov/mmwr/PDF/rr/rr4607.pdf . \n29 https://stacks.cdc.gov/view/cdc/76558 . \n30 https://stacks.cdc.gov/view/cdc/76558 . \n31 https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5126a5.htm . \n32 https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5126a5.htm . \n3 \n Boostrix (GSK)  200533                    200534                  24 days  \nAdacel (Sanofi)  200535                    200536                  20 days  \nMenactra (Sanofi)  200537                    200538                  27 days  \nGardasil (Merck)  200639                    200640                  21 days  \nHiberix (GSK)  200941 200942                 30 days  \nPrevnar 13 (Pfizer)  201043 201044                   0 days  \nMenveo (GSK)  201045 201046                 19 days  \nGardisil -9 201447 201548                 78 days  \nMenQuadfi (Sanofi)  202049 202050                 62 days  \nVaxneuvance  (Merck)  202251 202252                   5 days  \nPriorix (GSK)  202253 202254                 17 days  \nPrevnar 20 (Pfizer)  202355 202356                 56 days  \n \n \n \n \n33 https://cdc.gov/mmwr/preview/mmwrhtml/rr5517a1.htm . \n34 https://cdc.gov/mmwr/preview/mmwrhtml/rr5517a1.htm . \n35 https://archive.cdc.gov/www_cdc_gov/media/pressrel/r051109.htm . \n36 https://archive.cdc.gov/www_cdc_gov/media/pressrel/r051109.htm .  \n37 https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5407a1.htm . \n38 https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5407a1.htm . \n39 https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5602a1.htm . \n40 https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5602a1.htm . \n41 https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5836a5.htm . \n42 https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5836a5.htm . \n43 https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5911a1.htm . \n44 https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5911a1.htm . \n45 https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5909a5.htm . \n46 https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5909a5.htm . \n47 https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6411a3.htm . \n48 https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6411a3.htm . \n49 https://www.cdc.gov/acip/grade/mening -MenACWY -TT.html . \n50 https://www.cdc.gov/mmwr/volumes/69/rr/rr6909a1.htm . \n51 https://www.cdc.gov/mmwr/volumes/71/wr/mm7137a3.htm . \n52 https://www.cdc.gov/mmwr/volumes/71/wr/mm7137a3.htm . \n53 https://www.cdc.gov/mmwr/volumes/71/wr/mm7146a1.htm .  \n54 https://www.cdc.gov/mmwr/volumes/71/wr/mm7146a1.htm . \n55 https://www.cdc.gov/mmwr/volumes/72/wr/mm7239a5.htm . \n56 https://www.cdc.gov/mmwr/volumes/72/wr/mm7239a5.htm . \n4 \n  \n \nSLIDES 15 -18: CONTROLS; SAFETY DURATIONS; STATISTICAL POWER  \n \nWhen our law firm seeks to establish causation between a vaccine product and a claimed injury, \nthe primary source for proving such claims is the data from clinical trials for that product. This is \nbecause most of the studies conducted after  licensure are retrospective epidemiological studies \nwhich are not deemed reliable for supporting causation. Hence, obtaining and reviewing the \nclinical trial data for each vaccine has been an important part of our legal work.  \n \nClinical trials are also critical for assuring safety, especially for vaccines. This is because after a \nvaccine is licensed, many consider it unethical to conduct a placebo -controlled trial and without a \nproper trial , determining causation between a vaccine and a claimed adverse event is extremely \ndifficult.  \n \nThe control group in clinical trials for a new drug will often receive a placebo.  As defined by the \nCDC  and FDA , a placebo is , “[a] substance or treatment that has no effect on living  beings”  and \nan “inert substance,” respectively.57 The importance of a placebo control group is explained by the \nNIH as follows: “In undertaking a clinical trial, researchers … want to be as certain as possible \nthat the results of the testing show whether or not a treatment is safe and effective. The ‘gold \nstandard’ for testing interventions in people is the ‘randomized, placebo -controlled’ clinical trial. ... \nA placebo is an inactive substance that looks like the drug or treatment being tested. ” \n \nHow well the “pivotal trial ” (the  trial FDA relies upon to license a vaccine ) can determine safety \ndepends on, among other factors, (i) the duration that safety is reviewed in the trial, (ii) the number \nof participants in the trial, and (iii) the use of a valid control, which should be a placebo or another \nvaccine for the same disease that has already been licensed based on a trial that properly assessed \nsafety. Each of these factors is essential because:  \n  \n• If the control group receives a control whose safety has not been established in its own \nclinical trial, the control cannot be relied upon to provide a baseline of what is “safe.”  \n \n• If the duration for which safety is reviewed is limited, the trial will miss safety issues that \narise after the time for which safety is reviewed.  \n \n• If there are not enough participants, i.e. it is not sufficient ly power ed, it will not detect \nsafety issues that occur at a rate not detectible at th e lower level of power.  \n \nThe following is a list of every  stand -alone routine vaccine on the CDC’s childhood vaccine \nschedule and a short discussion regarding the pivotal trial FDA relied upon to license each , with \ncitation to the FDA sources:   \n \n• Hep B vaccine (CDC schedule: birth, 1 month, and 6 months)  \n \n57 \nhttps://www.cdc.gov/vaccines/glossary/?CDC_AAref_Val=https://www.cdc.gov/vaccines/terms/glossary.html#headin\ng-p; https:// www.fda.gov/media/130326/download . \n5 \n o Recombivax HB (Merck) : licensed for babies based on trials with no placebo \ncontrol and 5 days of safety monitoring after injection.58  \no Engerix B (GSK) : licensed for babies based on trials with no placebo control and \n4 days of safety monitoring after injection.59  \n• DTaP vaccine (CDC schedule: 2, 4, 6, and 15 months, and 4 years)  \no Infanrix (GSK) : licensed for babies based on trials with no placebo control (DTP \nvaccine used as a control) and up to 30 days of safety review after injection.60 DTP, \nused as the control was not licensed in a placebo -controlled trial and  DTP has, in \nmost studies looking at this issue, repeatedly been found to increase mortality in \ninfants, meaning DTP -vaccinated infants die at far higher rates than their equally \nsituated non -vaccinated peers.61 \no Daptacel (Sanofi) : licensed for babies based on trials with no placebo control (DT \nor DTP vaccine used as control) and 2 months of safety review after injection, \nexcept one trial which had 6 months of safety review, no control, and 1,454 children. \nIn that trial, “[w]ithin 30 days following any dose of DAPTACEL, 57 (3.9% ) \nsubjects reported at least one  serious adverse event.”62 See Infanrix bullet point \nregarding DTP.  \n• PCV vaccine (CDC schedule: 2, 4, 6, and 12 months)  \no Prevnar 13, PCV -13 (Wyeth, part of Pfizer) : licensed for babies based on trials \nwith no placebo control (Prevnar 7 used as a control, which was licensed based on \na trial in which the control was an “Investigational meningococcal group C \nconjugate vaccine,” meaning another experimental vaccine) and  6 months of safety \nreview after injection which found, “[s]erious adverse events reported following \nvaccination in infants and toddlers occurred in 8.2% among Prevnar 13 recipients \nand 7.2% among Prevnar recipients.”63 \no Vaxneuvance PCV -15 (Merck) : licensed for babies based on trials with no \nplacebo control (Prevnar 13 used as the control) and up to 6 months of safety review \nafter injection finding that, “[a]mong children who received VAXNEUVANCE \n(N=3,349) or Prevnar 13 (N=1,814) … serious adverse ev ents up to 6 months \nfollowing vaccination with the 4 -dose series were reported by 9.6% of \nVAXNEUVANCE recipients and by 8.9% of Prevnar 13 recipients.” Deemed “safe” \nbecause, “[t]here were no notable patterns or numerical imbala nces between \nvaccination groups.”64 \no Prevnar 20, PCV -20 (Pfizer) : licensed for babies based on trials with no placebo \ncontrol (Prevnar 13 used as the control), up to 6 months of safety review after \ninjection, and that showed high rates of serious events (this time broken up into two \ncategories – “serious adverse events ” and “newly diagnosed chronic medical \n \n58 See Section 6.1 at https://www.fda.gov/media/74274/download .  \n59 See Section 6.1 at https://www.fda.gov/media/119403/download . \n60 See Section 6.1 at https://www.fda.gov/media/75157/download . \n61 https://icandecide.org/wp -content/uploads/2021/06/2021.01.28 -Letter -to-Special -Rapporteur -on-Poverty.pdf . \n62 See Section 6.1 at https://www.fda.gov/media/74035/download ; https://www.fda.gov/safety/reporting -serious -\nproblems -fda/what -serious -adverse -event .  \n63 See Section 6.1 at https://www.fda.gov/media/107657/download ; https://www.fda.gov/media/76076/download . \n64 See Section 6.1 at https://www.fda.gov/media/150819/download .  \n6 \n conditions”) in both vaccine groups (experimental and control) but deemed “safe” \nbecause “no notable patterns or imbalances between vaccine groups.”65 Meaning, \nPCV -20 was licensed based on a clinical in which PCV -15 was the control, PCV -\n15 was licensed based on a clinical trial in which PCV -13 was the control, PCV -13 \nwas licensed based on a clinical trial in which PCV -7 was the control, and PCV -7 \nwas li censed based on a clinical trial in which another experimental, unlicensed \nvaccine was the control, and in each of these trials the serious adverse events in \nboth the control and experimental groups were similar which was sufficient for a \nfinding of “safe”  for licensure by the FDA.  \n• Polio vaccine (CDC schedule: 2, 4, and 6 months, and 4 years)  \no IPOL (Sanofi) : licensed in 1990 for babies based on trials with no placebo control \nand 3 days of safety review after injection. Sanofi reports that, “Although no causal \nrelationship has been established, deaths have occurred in temporal association \nafter vaccination of i nfants with IPV.”66 (Note that IPOL is a  different  product than \nthe polio vaccine developed by Jonas Salk in the 1950s, which was discontinued in \nthe 1960s, including because it is “grown in vero cells, a continuous line of monkey \nkidney cells cultivated on microcarriers.” H ence, the Salk vaccine’s safety or \nefficacy was not relied upon to license IPOL .67) \n• Hib vaccine (CDC schedule: 2, 4, 6, and 12 months)  \no ActHIB (Sanofi) : licensed for babies based on trials with no placebo control \n(Hepatitis B vaccine used as control) and 30 days of safety review after injection \nduring which 3.4% experienced a serious adverse event but “[n]one was assessed \nby the investigators [Sonafi] as  related to the study of vaccines.”68  \no Hiberix (GSK) : licensed for babies based on trials with no placebo control \n(unlicensed Hib vaccines and HibTITER used as the control) and 31 days of safety \nreview after injection.69 \no Liquid PedvaxHIB (Merck) : licensed for babies based on trials with no placebo \ncontrol (Lyophilized PedvaxHIB used a control) and 3 days of safety review after \ninjection.70 (Note that Lyophilized PedvaxHIB was tested in a trial in which the \ncontrol group was given placebo, OPV, and DTP but there is no indication \nLyophilized PedvaxHIB was ever licensed.71) \n \n65 See Section 6.1 at https://www.fda.gov/media/149987/download ; https://www.fda.gov/media/150459/\ndownload?attachment .  \n66 See pages 14 -17 at https://www.fda.gov/media/75695/download . \n67 See pages 1 at https://www.fda.gov/media/75695/download ; https://pubmed.ncbi.nlm.nih.gov/6740101/ ; https://\nadmin.phe -culturecollections.org.uk/media/122249/vero -cell-line-profile.pdf ;  https://www.atcc.org/products/all/ccl -\n81.aspx#characteristics . \n68 See Section 6.1 at https://www.fda.gov/media/74395/download ; see page 8 at http://wayback.archive -\nit.org/7993/20170723144656/https:/www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/\nUCM244597.pdf .  \n69 See Section 6.1 at https://www.fda.gov/media/77017/download ; see pages 20 -21 at http://wayback.archive -\nit.org/7993/20170722072902/https:/www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/\nUCM182550.pdf .  \n70 See page 6 -8 at https://www.fda.gov/media/80438/download .  \n71 See page 6 -8 at https://www.fda.gov/media/80438/download . \n7 \n • Rotavirus vaccine (CDC schedule: 2, 4, and 6 months) (Note that every vaccine on the \nCDC childhood schedule is given via injection, except for one flu vaccine given by nasal \nspray and the rotavirus vaccines, which are given by oral drops in the mouth.)  \no Rotarix (GSK) : licensed for babies based on trials without a placebo control (the \ncontrol group received an oral drop that included Dextran, Sorbitol, Amino Acids, \nDulbecco’s Modified Eagle Medium, and Xanthan) and 31 days of safety review \nafter oral dose and up to a yea r in some trials to watch for cases of intussusception. \nThere were more deaths in the group receiving Rotarix than the control group. \n“During the entire course of 8 clinical studies (Studies 1 to 8), there were 68 \n(0.19%) deaths following ad ministration of ROTARIX (n = 36,755) and 50 (0.15%) \ndeaths following placebo administration (n = 34,454). The most commonly \nreported cause of death following vaccination was pneumonia, which was observed \nin 19 (0.05%) recipients of ROTARIX and 10 (0.03%) p lacebo recipients (RR: 1.74, \n95% CI: 0.76, 4.23).”72 \no RotaTeq (Merck) : licensed for babies based on trials without a placebo control \n(the control group received an oral drop that included Polysorbate -80, Tissue \nCulture Medium, Fetal Bovine Serum, and Sodium Phosphate) and 42 days of \nsafety review after each oral dose and up t o a year to watch for cases of \nintussusception.73  \n• Flu vaccine (CDC schedule: 6 and 7 months and then annually)  \no The formulation for each  influenza vaccine  changes annually and there is no \nclinical trial carried out for each new formulation. In any event, none of the clinical \ntrials for the original formulation of any injected influenza vaccine for children had \na pla cebo control group. In 1980, FDA licensed Fluzone (IIV3) without assessing \nits safety against a placebo control.74 Nonetheless, Fluzone (IIV3) was used as the \ncontrol in the trials relied upon to license Afluria (IIV3) in 2007 and Fluzone (IIV4) \nin 2013 for children .75 Then, Fluzone (IIV4), Fluarix (IIV3), or Havrix were used \nas the controls in the clinical trials supporting the licensure of FluLaval (IIV4).76 \nThe safety of these products therefore rests on the safety of Fluzone (IIV3) which \nwas licensed for pediatric use based on a trial without any control, let alone a \nplacebo control.77 Similarly, Fluarix (IIV4) was licensed for children in 2012 based \n \n72 See Section 6.1 at https://www.fda.gov/media/163009/download  (claims used a placebo);  see pages 23 -24 at \nhttp://wayback.archive -it.org/7993/20170722073219/https:/www.fda.gov/downloads/BiologicsBlood\nVaccines/Vaccines/ApprovedProducts/UCM133580.pdf  (explains “placebo” included all the foregoing ingredients).  \n73 See Section 6.1 at https://www.fda.gov/media/75718/download  (claims used placebo); see page 445 et al . at \nhttps://icandecide.org/wp -content/uploads/2023/06/rotateq_placebo.pdf .  \n(explains the “placebo” included all the foregoing ingredients).  \n74 https://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM619664.pdf ; \n(Research ers did conduct one efficacy trial for Fluzone (IIV3) long after  it was licensed which found that “the rate of \nhospitalization was actually higher in the vaccine group than in the placebo group” with 60% more vaccinated than \nunvaccinated children being hospitalized for insertion of ear draining tubes. \nhttps://www.ncbi.nlm.nih.gov /pubmed/ 14506120 ). \n75 https://www.fda.gov/media/81559/download  (placebo control only used in adult trials but never in trials to license this \nvaccine for children); https://www.fda.gov/media/119856/download .  \n76 https://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM619548.pdf . \n77 https://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM619664.pdf . \n8 \n on a trial using Prevnar 13, Havrix and/or Varivax as controls; Fluarix (IIV4) was \nthen used as the control to license Afluria (IIV4) in 2016.78 This means Afluria \n(IIV4) was licensed because it was deemed as safe as Fluarix (IIV4), and that \nvaccine was licensed because it was deemed as safe as Prevnar 13, Havrix, or \nVarivax. However, the latter two were licensed without a placebo control; and \nPrevnar 13 was licensed because it was as safe as Prevnar, but that vaccine was \nonly licensed because it was as safe as “an investigational meningococcal group C \nconjugate vaccine. ” Hence, none of those vaccines had its safety profile established \nbased on any placebo -controlled clinical trial. The only exception is one inhaled \ninfluenza vaccine whose original trial had a placebo, but its formulation changes \nevery year and is not safet y tested in any trial.79 \no The following chart includes each licensed trivalent (IIV3) and quadrivalent (IIV4) \ninfluenza vaccine:80 \n \n \n \n78 https://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM220624.pdf  (44% and \n45% of the Fluarix (IIV4) and comparator vaccine group, respectively, reported an unsolicited adverse event within 28 \ndays and 3.6% and 3.3%, respectively, reported a serious adverse reaction).  \n79 https://www.fda.gov/media/160349/download?attachment ;  https://www.fda.gov/media/73706/downloads .  \n80 Supporting  references  for each vaccine  in the table:  Fluzone  (IIV3)  \n(https://www.fda.gov/ media/170019/download  (As reflected in section 14.1, nineteen years after licensure \na small effi cacy,  not safety,  trial had a small  group  of children  receiving  a placebo  which  did not contribute  to any \nsafety  finding  for this product;  ironically,  had this trial been conducted  pre-licensure,  and relied upon for safety, it would \nhave raised a serious safety issue since “the rate of hospitalization  was actually higher in the vaccine group than in the \nplacebo group” with 60% more vaccinated  than unvaccinated  children  hospitalized  for insertion  of ear drainage  \ntubes )); Fluvirin  (IIV3)  (https://www.fda.gov/media/75156/download ); Fluarix (IIV3) \n(https://www.fda.gov/media/84804/download ); Flulaval  (IIV3)  (https://www.fda.gov/media/74537/download ); \nAfluria  (IIV3) (https://www.fda.gov/media/81559/download  (states  placebo  used in adult  trials  but not in trials for \nchildren); Flucelvax (IIV3)  (https://www.fda.gov/media/85322/download ); Fluarix  (IIV4)  \n(https://www.fda.gov/media/79278/download , states  placebo  used in adult  trials  but not in trials for children); Flublok \n(IIV3)  (https://www.fda.gov/media/179778/download ); Fluzone  (IIV4)  \n(https://www.fda.gov/media/170019/download ); FluLaval  (IIV4)  (https://www.fda. gov/media/115785/download ); \nAfluria (IIV4) (https://www.fda.gov/media/117022/download ); Flucelvax  (IIV4)  \n(https://www.fda.gov/media/115862/download , states  placebo  used in adult  trials but not in trials for children).  \n \n9 \n                       \n \nAs reflected in this chart, the safety of many influenza vaccines rests on a trial that \nused Fluzone (IIV3) as a control or another vaccine that was licensed based on \nusing Fluzone (IIV3) as a control. But Fluzone (IIV3) was licensed based on a small \ntrial without any control. Researchers did conduct one efficacy (not safety) trial for \nFluzone (IIV3) long after  it was licensed which found that “the rate of \nhospitalization was actually higher in the vaccine group than in the placebo group” \nwith 60% more vaccinated than unvaccinated children being hospitalized for \ninsertion of ear drainage tubes.81 \n• MMR vaccine (CDC schedule: 12 months and 4 years)  \no M-M-R-II (Merck) : licensed based on a trial with a total of 834 children, no \ncontrol group, and that reviewed safety for 42 days during which one -third of \nvaccinated participants developed gastrointestinal and a third respiratory issues.82 \n \n81 https://pubmed.ncbi.nlm.nih.gov/14506120/ .  \n82 See clinical trial reports for M -M-R-II at https://www.sirillp.com/wp -content/uploads/2023/07/MMRII -FOIA.pdf . \npackage insert ; see package insert for M -M-R-II https://www.fda.gov/media/75191/download  (The package insert for \nM-M-R-II does not list any pivotal trial as a basis for determining this product was safe for licensure, presumably \nbecause the trial relied upon to license this product could not establish it was safe for licensure.); see \nhttps://icandecide.org/wp -content/uploads/2023/08/MMR -I-clinical -trials -safety -tables.pdf  (The original MMR’s \nclinical trial was also underpowered, among other deficiencies,  and showed a similarly high rate of gastrointestinal, \nrespiratory and other issues, as compared to the small untreated control group. Also note that the original MMR was \na different product that did not include millions of pieces of human DNA and cellular debris, as does M -M-R-II.). \nBecause viruses multiply in cells, living cells are used to grow viruses for vaccine production, including the cultured \ncell lines of aborted fetuses. Two such cell lines are MRC -5 and WI -38, which are described by a company that sells \nthem as follows: “T he MRC -5 cell line was derived from normal lung tissue of a 14 -week -old male embryo” and the \n“WI-38 cell line is the first human diploid cell line to be used in human vaccine preparation … [and] were isolated \nfrom the lung tissue of a 3 -month -old, female, embryo.” https://www.atcc.org/products/ccl -75; \nhttps://www.atcc.org/products/ccl -171. The ingredients of chickenpox, rubella, and hepatitis A vaccines each include \ncellular and DNA pieces from these fetal cell lines. The ingredient list for Varivax (chicken -pox) includes “MRC -5 \nhuman diploid cells including DNA & protein,” for MMR -II (whi ch includes rubella) includes “WI -38 human diploid \nlung fibroblasts,” and for Havrix (hepatitis A) includes “MRC -5 cellular proteins.” \nhttps://web.archive.org/web/20241120002123/https://www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendices/\n \n\n10 \n o Priorix (GSK) : licensed based on trials with no placebo control (M -M-R-II used \nas the control) and 6 months of safety review after injection in which both vaccine \ngroups had a high rate of serious adverse events (2.1% of Priorix group and 1.9% \nof M -M-R-II group), emerg ency room visits (10.1% of Priorix group and 10.4% of \nM-M-R-II group), and new onset of chronic diseases (e.g., autoimmune disorders, \nasthma, type I diabetes, vasculitis, celiac disease, thrombocytopenia, and allergies) \n(3.4% of Priorix group and 3.7% of M -M-R-II group ).83  \n• Varicella vaccine (CDC schedule: 12 months and 4 years)  \no Varivax (Merck) : licensed based on trials with no placebo control (the purported \n“placebo” was actually an injection of 45 mg of neomycin per milliliter) and 70 \ndays of safety review after injection which included only one controlled trial of 956 \nchildren in which approx imately half received Varivax and half received the \ninjection of 45 mg of neomycin per milliliter, and there was one trial in which 32 \nchildren received Varivax and 29 children received nothing and then received \nVarivax eight weeks later; du ring this eight -week period, the Varivax group had \ndouble the rate of ear infection and a 50% increase in respiratory infection. As for \nserious adverse events, Merck did not consider any related to Varivax.84 \n• Hep A vaccine (CDC schedule: 12 and 18 months)  \no Havrix (GSK) : licensed based on trials with no placebo control (Engerix -B was \nused as a control) and 31 days of safety review after injection with a phone call \nfollow -up at 6 months.85 Note, as discussed above, Engerix -B was  licensed for \n \nb/excipient -table -2.pdf . As for the quantity of human DNA in each vial, for Varivax, as the FDA explains: “human \nMRC -5 cells are the substrate upon which the Oka strain of varicella is grown. In the process of isolating virus from \nthese cells, MRC -5 derived proteins and DNA are also obtained. The nearly 2 ug [2,000 nanograms] of unmodified \nmammalian DNA present in each dose of VARIVAX…” https://wayback.archive -\nit.org/7993/20170723031730/https:/www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/\nUCM142826.pdf . As for MMR -II, during Dr. Plotkin’s deposition, I asked: “Isn’t it true that MMR II contains \napproximately 150 nanograms cells substrate double -strand DNA and single -strand DNA per dose purposefully \nfragmented to approximately 215 base pairs in length?” Dr. Plotkin answered: “Yeah, that’s probably correct, yes.” \nhttps://icandecide.org/plotkintranscript/  at p. 328. See also https://soundchoice.org/wp -\ncontent/uploads/2021/01/epidemiologic -molecular -relationship -vaccine -manufacture -autism -prevalence.pdf ; \nhttps://pubmed.ncbi.nlm.nih.gov/26103708/  (See Table 3, reflecting an average of 142 nanograms of single -stranded \nDNA and 35 nanograms of double -stranded DNA in the rubella vaccine component of each dose of MMR -II; and an \naverage of 276 nanograms of single -stranded DNA and 35.74 nanograms of doub le-stranded DNA in each dose of \nHavrix). For DNA remaining in the final formulation, assuming pharma companies follow FDA’s guidance, they \nwould fragment “the DNA size to below approximately 200 base pairs.” \nhttps://www.fda.gov/media/113760/download  at pp.29 -30. Doing the math, supposing only 100 nanograms of double -\nstranded DNA remain, and are broken down into 200 base pair fragments, this equals approximately 463 billion pieces \nof human DNA from an aborted fetal cell line in each vaccine dose; doub le that number for single -stranded DNA. \nhttps://www.technologynetworks.com/tn/tools/copynumbercalculator . In addition to the human DNA, there is also an \nunspecified amount of human cellular debris in each vaccine dose. See also  https://thehighwire.com/ark -\nvideos/aborted -fetal-tissue -in-vaccines/ . \n83 See Section 6.1 at  https://www.fda.gov/media/189623/download ; see page 12 at https://pmc.ncbi.nlm.nih\n.gov/articles/instance/7192400/bin/piz010_suppl_supplementary_materials.docx . \n84 See Section 6.1 at https://www.fda.gov/media/76000/download ; see page 2 at https://pubmed.ncbi.nlm.nih.gov/\n6325909/ ; see Varivax  clinical reports at  https://www.sirillp.com/wp -content/uploads/2023/07/Varivax -clinical -\ntrials.pdf . \n85 See Section 6.1 at https://www.fda.gov/media/119388/download . \n11 \n babies based on trials with no placebo control and 4 days of safety monitoring after \ninjection.86 \no Vaqta (Merck) : licensed based on trials with no placebo control (an injection of \nAAHS, an aluminum adjuvant, and thimerosal, a form of mercury, were used as a \ncontrol) and up to 42 days of safety review after injection.87 Note that no placebo \ncontrol was used despite the fact the trials for Havrix and Vaqta occurred at roughly \nthe same time when there was no licensed Hepatitis A vaccine yet licensed.  \n• Tdap vaccine (CDC schedule: 11 years)  \no Adacel (Sanofi) : licensed based on trials with no placebo control (Td, for adult use, \nwas used as a control) and up to 6 months of safety review after injection.88 \no Boostrix (GSK) : licensed based on trials with no placebo control (DECAVAC or \nAdacel was used as a control) & up to 6 months of safety review after injection.89 \n• HPV vaccine (CDC schedule: 9 and 9 ½ years)  \no Gardasil 9 (Merck) : licensed based on trials in which safety was reviewed after \ninjection for 1 month in five of the clinical trials, 6 months in a lot consistency trial, \nand 4 years in one trial of women aged 16 to 26 years. These Gardasil 9 trials were \neither not controll ed or used Gardasil 4 as the control, except for one trial in which \n306 participants received a placebo but only after receiving the full series of \nGardasil 4 injections .90 (Note that in  Gardasil 4 ’s clinical trial, controls received an \naluminum adjuvant, AAHS, except 320 people labeled “Saline Placebo” who \nactually received all vaccine ingredients except antigens and AAHS; and across all \nthese trials, 2 -3% of participants receiving vaccine or alumi num adjuvant – a \nsubstance used to induce  autoimmunity  in lab animals – had a suspected \nautoimmune disorder.91) \n• Men4 vaccine (CDC schedule: 11 and 16 years)  \no Menactra (Sanofi) : licensed based on trials with no placebo control (Menomune \nused as the control) and up to 6 months of safety review after injection.92 Note \nMenomune was licensed without a placebo -controlled trial; rather, the safety \nsection of the package insert for Menomune lists the same trial used to license \nMenactra as the basis for the safety of Menomune despite the fact Menomune was \nused as a cont rol in that trial.93 \n \n86 See Section 6.1 at https://www.fda.gov/media/119403/download . \n87 See Section 6.1 at https://www.fda.gov/media/74519/download  (using term “placebo”); see clinical trial report  at \n454 https://www.nejm.org/doi/pdf/10.1056/NEJM199208133270702?articleTools=true  (explains the purported \n“placebo” included the foregoing ingredients).  \n88 See Section 6.1 at https://www.fda.gov/media/119862/download . \n89 See Section 6.1 at https://www.fda.gov/media/124002/download . \n90 See pages 17 -19 at https://wayback.archive -it.org/7993/20190423065200/https:/www.fda.gov/downloads/\nBiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM429166.pdf . \n91 See https://www.fda.gov/media/74350/download ; https://pubmed.ncbi.nlm.nih.gov/27417999/ .  \n92 See Section 6.1 at https://www.fda.gov/media/75619/download . \n93 See https://archive. org/details/menomune -a-c-y-w-135-prescribing -information .  \n12 \n o Menveo (GSK) : licensed based on trials with no placebo control (Menactra, \nBoostrix, or other vaccines used as a control) and up to 6 months of safety review \nafter injection.94 \no MenQuadfi (Sanofi) : licensed based on trials with no placebo control (Menveo or \nother vaccines used as a control) and up to 6 months of safety review after \ninjection.95 Thus, Menomune was licensed without a placebo -controlled trial and \nwas then used as the control to license Menactra; Menactra is then used as the \ncontrol to license Menveo; and then Menveo is used as the control to license \nMenQuadfi.  \n \nFor completeness, the following is a list of the stand -alone non-routine vaccine s on the CDC’s \nchildhood vaccine schedule and a short discussion regarding the pivotal trial FDA relied upon to \nlicense each with citation to the FDA sources:   \n \n• COVID -19 vaccine (CDC schedule: 6, 7, and 10 months, and then annually.)  \no Comirnaty (Pfizer) : licensed only for children 12 years of age and older (not for \nbabies) and had a placebo control (note that the placebo controls were vaccinated \nduring the trial), 6 months of safety review after injection, and a total of 3,014 \nparticipants.96 Note that Pfizer failed to report a serious injury in at least one child \nparticipant in its trial who received the vaccine.97   \no Spikevax (Moderna) : licensed only for children 12 years of age and older (not for \nbabies) and had a placebo control (note that the placebo controls were vaccinated \nduring the trial), 6 months of safety review after injection, and a total of 3,726 \nparticipants.98 \n• MenB vaccine (CDC schedule: 10 years and older if indicated)  \no Bexsero (GSK) : licensed based on trials in which controls were administered \naluminum hydroxide and, in one trial with 120 adolescents, saline injection \nfollowed by injection of Menveo. FDA labels this an “active control,” not a \n“placebo control” trial.99 \no Trumenba (Pfizer) : licensed based on trials with no placebo control group other \nthan 12 people in a dose -ranging phase II study (otherwise the controls were \ninjection of Gardasil+placebo, dTaP -IPV+placebo, HepA+placebo, or \n \n94 See Section 6.1 at https://www.fda.gov/media/78514/download . \n95 See Section 6.1 at https://www.fda.gov/media/137306/download .  \n96 See Section 6.1 at https://www.fda.gov/media/151707/download?attachment . \n97 https://icandecide.org/wp -content/uploads/2023/07/3 -08-2022 -Ltr-to-Dr.-Paul-Richards -FDA -re-Maddie -de-\nGaray.pdf .    \n98  https://www.fda.gov/media/155675/download .  \n99 See pages 14 -15 at https://wayback.archive -it.org/7993/20190425012223/https:/www.fda.gov/\ndownloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM434748.pdf ; see page 40 at https\n://wayback.archive -it.org/7993/20190423064855/https:/www.fda.gov/ downloads/BiologicsBloodVaccines/\nVaccines/ApprovedProducts/UCM434714.pdf . See pages 14 -15 at https://wayback.archive -\nit.org/7993/20190425012223/https:/www.fda.gov/ downloads/ BiologicsBloodVaccines/Vaccines/ApprovedProducts/\nUCM434748.pdf ; see page 40 at https://wayback.archive -\nit.org/7993/20190423064855/https:/www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/\nUCM434714.pdf . \n13 \n Menactra+Adacel+placebo and 30 days of safety review after injection for one of \nthe three trials and up to 11 months in the other two trials.100 \n• PPSV23 vaccine (2Y+ if indicated)  \no Pneumovax 23 (Merck) : licensed for children 2 years and older although there is \nno indication that there was any clinical trial involving anyone younger than 16 \nyears of age that the FDA relied upon to license this vaccine.101 \n• Dengue vaccine (6Y+ if previously had dengue and live in area dengue is endemic)  \no Dengvaxia (Sanofi) : licensed based on a trial with 11,474 children receiving a \nplacebo control (saline injection), over 35,000 children in the trial, and 5 years of \nsafety review after injection. Meaning, the last listed vaccine on the CDC’s \nchildhood vaccine schedule is th e only vaccine that underwent a longer -term \nplacebo -controlled trial prior to licensure with a larger number of children.102 \nCareful study of this vaccine revealed that children under 6 years old had an \nincreased risk of severe harm and death from this vaccine and that children older \nthan 6 who had never had dengue and received this vaccine likewise had a seriously \nincreased ri sk of severe harm and death. Hence, this vaccine is only indicated for \nolder children who have previously had dengue. “Those not previously infected are \nat increased risk for severe dengue disease when vaccinated and subsequently \ninfected with dengue virus .”103 This vaccine is only recommended for children in \nendemic dengue areas and dengue is not endemic in the  U.S.104 \n \nThe FDA source material for each vaccine, as set forth above, reflects:  \n \n• None of the childhood vaccines recommended for routine use by the CDC were licensed \nbased on a placebo -controlled trial nor on a trial where the vaccine used as a control was \nitself licensed based on a placebo -controlled trial.  Rather, in each trial, there was either no \ncontrol group or another vaccine or vaccine ingredient was used as a control, and none of \nthose control vaccines were licensed based on a placebo -controlled trial.  \n \n• None of the childhood vaccines recommended for routine use by the CDC (save for one \nlimited HPV trial) were licensed based on trials that had long -term safety follow -up after \nadministration. Rather, safety was reviewed for a limited period, often no more t han \nmonths, and often only days or weeks after administration.  \n \n• None of the childhood vaccines recommended for routine use by the CDC were licensed \nbased on trials which were appropriate to assess whether the vaccine causes more harm \n \n100 See page 4 at  https://wayback.archive -it.org/7993/20190425012035/https:/www.fda.gov/downloads/\nBiologicsBloodVaccines/Vaccines/ApprovedProducts/UCM548305.pdf ; see pages 9 -10 at https://wayback.archive -\nit.org/7993/20190423065758/https:/www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProducts/\nUCM424626.pdf . \n101 See Sections 6.1 and 14.1 https://www.fda.gov/media/80547/download . \n102 See page 10 at https://www.fda.gov/media/125481/download ; see page 4 at  https://www.fda.gov/media/124379/\ndownload . \n103 https://www.fda.gov/media/124379/download .  \n104 https://www.usgs.gov/faqs/what -constitutes -united -states -what -are-official -definitions .  \n14 \n than it prevents. This is because, as seen from the FDA source material, their pivotal trial \ntypically had only  hundreds or a few thousand children, severely limiting the power of \nthese trials to assess safety and therefore, not sufficient to conclude, statistically, that the \ntrialed products prevent more serious harms and deaths than they cause.  \n \nThe FDA documentation reflects that, as the Secretary of Health and Human Services, Robert F. \nKennedy Jr., has previously explained, none of the routine vaccines on the CDC childhood \nschedule (which does not include the dengue vaccine as it’s not routine) underwent a long -term \nplacebo -controlled trial, nor just a placebo -controlled trial (or even a trial where the vaccine used \nas a control was previously established as safe in a long -term placebo -controlle d trial).  \n \n \nSLIDES 26 -27: DTP VACCINE  \n \nDTP vaccine is the most widely used vaccine in the world . It was not licensed based on a placebo -\ncontrolled trial, and studies conducted in recent decades have found that DTP increases mortality. \nA landmark study on this issue was funded by the Ministry of Foreign Affairs of Denmark and the \nEuropean Union and publ ished in 2017.105 After comparing children vaccinated with DTP to \nchildren that received no vaccines, it found that that DTP -vaccinated children were 10 times more \nlikely to die in the first 6 months of life. The study therefore concluded:  \n \nAll currently available evidence suggests that DTP vaccine may kill \nmore children  from other causes than it saves from diphtheria, \ntetanus or pertussis.106 \n \nThis study, and others, found that children vaccinated with DTP were dying from causes never \nassociated with the vaccine, such as respiratory infections, diarrhea, and malaria.107 This indicated \nthat, while DTP reduced the incidence of diphtheria, tetanus, and pertussis, it increased \nsusceptibility to other infections.108  \n \nA 2014 review of DTP and mortality by the WHO’s Strategic Advisory Group of Experts (SAGE), \nidentified 16 studies that compared death rates between children receiving DTP and children not \nreceiving DTP, and found that a majority of the 16 studies indicated that DTP increases \nmortality.109 SAGE discounted the studies showing DTP increases mortality on the basis that: (i) \nthese studies were not “randomized” ( i.e., children were not randomly assigned to either receive \nor not receive DTP, potentially introducing bias); (ii) “OPV [Oral Polio Vaccine] was administered \nconcomitantly with DTP in most included studies ” and hence it “was not possible to separate any \npossible effects of DTP from OPV in the available studies”; and (iii) these studies were often \n \n105 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5360569/  (https://perma.cc/6R29 -ZSHK ).  \n106 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5360569/  (https://perma.cc/6R29 -ZSHK ).  \n107 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5360569/  (https://perma.cc/6R29 -ZSHK ).  \n108 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5360569/  (https://perma.cc/6R29 -ZSHK ).  \n109 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5360569/  (https://perma.cc/6R29 -ZSHK ). \n15 \n conducted in communities with existing so -called “herd immunity” that could have introduced \nfurther bias.110 \n \nThe 2017 study was designed to avoid these limitations stated by SAGE. It addressed the \n“randomized” issue by using data whereby vaccines were administered based on birthdates, an \naccepted form of randomization.111 It addressed the “OPV with DTP” issue by comparing children \nreceiving no vaccines with those receiving only DTP.112 It addressed the “herd immunity” issue by \nlooking at death rates at the time of the introduction of DTP in that region.113 The result was the 2017 \nstudy discussed above. And because placebo -controlled trials of DTP are considered unethical, even \nthough a placebo -controlled trial was never conducted to license this product, the 2017 study on DTP \nand morality is likely the best  available evidence that will exist addressing whether DTP kills more \nchildren than it saves.  \n \nDTP policy has not, however, changed globally, even after another study published in 2018, which \nagain did not have the limitations identified by SAGE in 2014, and which again found DTP \nincreases mortality.114 This time the study looked at children between 6 and 35 months of age. The \n2018 study compared children receiving DTP, who were generally healthier and had better \nnutritional status, with children who did not receive DTP and who generally were unhealthier  and \nhad worse nutritional status. There, the children who did not receive DTP should have had worse \nhealth outcomes because they were generally unhealthier and had worse nutrition. The result:  \n \nAlthough having better nutritional status and being protected against \nthree infections, 6 -35 months old DTP -vaccinated children tended \nto have higher mortality than DTP -unvaccinated children. All \nstudies of the introduction of DTP have found increased over all \nmortality.115 \n \nA non -profit group contacted UNICEF, a primary distributor of DTP vaccine, regarding these studies, \nasking it to provide proof that the studies showing DTP increased mortality were incorrect. UNICEF \nasked CDC to help it respond to this request , but when CDC sent a proposed response to UNICEF, \nUNICEF asked CDC, “why we cannot prove or disprove this claim despite the fact that this issue \nhas been followed since 2001.”116 The email exchange between CDC and UNICEF does not appear \n \n110 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5360569/  (https://perma.cc/6R29 -ZSHK ). As an example of the \nnecessity for utilizing randomization to avoid bias, unvaccinated children often do not receive vaccines because they are \nvery frail, malnourished, or sick, and hence more likely to die irrespective of vaccination. Thus, the unvaccinat ed group \nis often sicker than the vaccinated group, making the vaccine appear safer. By randomly picking which children receive \nor do not receive the DTP vaccine, a researcher can avoid this type of bias.  \n111 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5360569/  (https://perma.cc/6R29 -ZSHK ).  \n112 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5360569/  (https://perma.cc/6R29 -ZSHK ).  \n113 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5360569/  (https://perma.cc/6R29 -ZSHK ).  \n114 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5868131/pdf/fpubh -06-00079.pdf  (https://perma.cc/7F7U -\nZZWJ ). \n115 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5868131/pdf/fpubh -06-00079.pdf  (https://perma.cc/7F7U -\nZZWJ ). \n116 https://icandecide.org/UNICEF -Emails . \n16 \n to seriously consider the data or studies but, rather, appeared to view them as a public relations issue.  \n \n \nSLIDES 30 : IMPACT OF IMMUNITY ON MARKET FORCES  \n \nPrior to 1986, when there were only 3 routine vaccines totaling 7 injections,117 the financial \nliability related to injuries from these products resulted in companies exiting the market.118 Instead \nof allowing economic interests to drive innovation of safer vaccine products, the National \nChildhood Vaccine Injury Act of 1986 (the “1986 Act”) gave pharmaceutical companies immunity \nfor vaccine injuries for those products and any routine childhood vaccine added to CDC’s schedule \nthereafter.119  \n \nAs of 2025, CDC’s maternal and childhood schedules lists 19 vaccines totaling 84 injections, \nvirtually all of which were licensed after 1986 by companies conducting clinical trials with the \nknowledge they would generally not be liable for any injuries caus ed by their vaccine products .120 \nThe following graphic reflects the routine vaccines, both injected and oral, an infant following the \nCDC’s vaccine schedule would receive in utero and up to 12 months of age in 1986 versus 2025:  \n  \n \n \nThe following chart reflects all routine and shared clinical decision -making  vaccines ( COVID -19 \nand MenB vaccines) a child would receive in 1983 versus 2025:  \n \n \n117 https://www.cdc.gov/vaccines/schedules/images/schedule1983s.jpg . \n118 Bruesewitz v. Wyeth , 562 U.S. 223  (2011)  (“the remaining manufacturer [of DTP] estimated that its potential tort \nliability exceeded its annual sales by a factor of 200”); Institute of Medicine, Adverse Events Associated with \nChildhood Vaccines , at 2 (1994), https://pubmed.ncbi.nlm.nih.gov/25144097/  (By 1986, “litigation costs associated \nwith claims of damage from vaccines had forced several companies to end their vaccine research and development \nprograms as well as to stop producing already licensed vaccines.”).  \n119 42 U.S.C. § 300aa -11 (“No person may bring a civil action for damages … against a vaccine administrator or \nmanufacturer … for damages arising from a  vaccine -related injury or death  associated with the administration of a \nvaccine”); Bruesewitz v. Wyeth , 562 U.S. 223  (2011)  (“[W]e hold that the National Childhood Vaccine Injury Act pre -\nempts all design -defect claims against vaccine manufacturers brought by plaintiffs who seek compensation for injury \nor death caused by a vaccine side effects.”).  \n120 https://www.cdc.gov/vaccines/parents/by -age/pregnancy.html ; https://www.cdc.gov/vaccines/schedules/ down\nloads/child/0 -18yrs -child -combined -schedule.pdf  (assumes each vaccine given individually and COVID -19 vaccine \ngiven annually).  \n\n17 \n  \n \nBecause companies remain liable for injuries  caused by  drugs , this provides an incentive to \nconduct long -term placebo -controlled trials to confirm the safety of drug products before licensure \nto avoid financial loss after licensure. For example, the following chart includes what are reported \nas the four most profitable drugs sold by Pfizer as of 2019, along with the control and safety \nduration in their licensure trial:  \n \n \n \nIn contrast, for vaccine products, the economic incentive to assess safety prior to licensure was \nmostly eliminated by the 1986 Act.121 This is because long -term placebo -controlled trials for \nvaccine products do not make financial sense for companies seeking to maximize profits. To the \ncontrary, while assuring safety in drug trials is aligned with a company’s economic interest, it is \nin conflict when it comes to vaccine trials. This provides context for the fact that, as seen in the \nprior section, every routine childhood vaccine recommended by the CDC was licensed without a \nplacebo control; was monitored for safety after administration for typically six months or less, \nsometimes only days or weeks; and often had too few participants to detect safety  signals.  \n \nFurther, HHS and its agencies  have a structural conflict with regard to  vaccine safety . This is \nbecause HHS’s responsibility to  promote and defend vaccines conflicts with its safety duties.  \n \nBecause duties to promote an industry inherently conflict with duties to identify and address safety \nissues within that industry, outside of vaccines, these duties are often separated into independent \nagencies. For example,  DOT  promotes  transportation  while  safety  functions  are handled  by the \nindependent  NTSB.122 Similarly,  DOE  promotes  nuclear  power  while  safety  functions  are handled  \nby the independent  NRC.123 But with vaccines, these conflicting duties are handled by the same \nentity: HHS.  \n \n121 42 U.S.C. §§ 300aa -1 through 300aa -34. \n122 https://www.ntsb.gov/about/history/pages/default.aspx . \n123 https://www.nrc.gov/about -nrc/history.html ; https://www.energy.gov/ne/office -nuclear -energy . \n\n18 \n  \nMoreover, HHS is statutorily required to and does vigorously defend against vaccine injury claims. \nUnder the 1986 Act, one can bring a claim for a vaccine injury, but it is brought against the \nSecretary of HHS in the Vaccine Injury Compensation Program (“V ICP”). This further conflicts \nHHS, including because any safety issues identified can be used against HHS in the VICP.124 \nVaccines are the only consumer product I am aware of where the government defends industry \ninterests against consumers, instead of vice -versa.  \n \nThese structural conflicts in regulating vaccines can result in regulators viewing and conducting \nthemselves as partners with pharmaceutical companies rather than as regulators.  Moreover, once \nfederal regulators have heavily promoted vaccine products, something they do not do with drug \nproducts, later admitting they cause harms could result in a loss of public confidence in HHS, the \nFDA, and the CDC and its vaccine schedule . It could also result in liability to HHS where it would \nneed to pay out damages as the respondent to claims in the VICP and the Countermeasures Injury \nCompensation Program (“CICP”). These create intractable and concerning  structural conflicts \nwith regard to HHS addressing vaccine safety.  \n \n \nSLIDES 34 -37: IOM REPORTS  \n \nThe degree of thoroughness of the post -licensure vaccine safety literature can be seen from IOM \nreviews on vaccine safety paid for by HHS, CDC, and/or other federal health agencies.  \n \nIn 1991, at HHS’s request per the 1986 Act, the IOM issued a report that evaluated 22 reported \nserious injuries from pertussis and rubella vaccines.125 The IOM located sufficient science to \nsupport that 6 serious injuries are causally related to these vaccines, including acute \nencephalopathy (brain damage) and chronic arthritis.126 The IOM, however, found that studies had \nnot been conducted in order for it to conclude whether or not these vaccines caused 12 other \ncommonly reported serious injuries, including:  \n \nAutism, Aseptic Meningitis, Chronic Neurological Damage, \nGuillain -Barre Syndrome, Juvenile Diabetes, Learning Disabilities, \nAttention -Deficit Disorder, Thrombocytopenia127 \n \nIn 1994, again at HHS’s request per the 1986 Act, the IOM evaluated 54 commonly reported \nserious injuries and vaccines for diphtheria, tetanus, measles, mumps, polio, hep B, and Hib.128 \n \n124 42 U.S.C. § 300aa -12 (“In all proceedings brought by the filing of a petition [in VICP] the Secretary [of HHS] shall \nbe named as the respondent.”); https://www.congress.gov/106/crpt/hrpt977/CRPT -106hr pt977.pdf  (“DOJ attorneys \nmake full use of the apparently limitless resources available to them,” “pursued aggressive defenses in compensation \ncases,” “establish[ed] a cadre of attorneys specializing in vaccine injury” and “an expert witness program to challenge \nclaims.”);  https://uscfc.uscourts.gov/vaccine -programoffice -special -masters . \n125 https://nap.nationalacademies.org/read/1815/chapter/1 .  \n126 https://nap.n ationalacademies.org/read/1815/chapter/2#7 . \n127 https://nap.nationalacademies.org/read/1815/chapter/2#7 . \n128 https://www.nap.edu/read/2138/chapter/2#12 .  \n19 \n The IOM located sufficient science to support that 12 serious injuries are causally related to these \nvaccines, including death, thrombocytopenia, and GBS.129 The IOM, however, found that studies \nhad not been conducted in order for it to conclude whether or not these vaccines caused 38 other \ncommonly reported serious injuries, including:  \n \nArthritis, Aseptic Meningitis, Demyelinating diseases of the central \nnervous system, Insulin -Dependent Diabetes Mellitus, Myelitis, \nNeuropathy, Residual Seizure Disorder, Sensorineural Deafness, \nSudden Infant Death Syndrome, Sterility, Transverse Optic \nNeuritis130  \n \nThe IOM explained: “The lack of adequate data regarding many of the adverse events under study \nwas of major concern to the committee. Presentations at public meetings indicated that many \nparents and physicians share this concern.”131  \n \nFifteen years later, in 2012, the CDC and HRSA, paid the IOM to review what they stated were \nthe 158 most common injuries claimed to be caused by various childhood vaccines.132 The IOM \nlocated science to support that 18 serious injuries were causally related to these vaccines, including \npneumonia, meningitis, MIBE, and febrile seizures.133 The IOM, however, found that studies had \nnot been conducted in order for it to conclude whether or not these vaccines caused 135 other \ncommonly reported serious injuries, including:  \n \nAcute Disseminated Encephalomyelitis, Afebrile  Seizures, \nAmyotrophic Lateral Sclerosis, Arthralgia, Autoimmune Hepatitis, \nBrachial Neuritis, Cerebellar Ataxia, Chronic Headache, Chronic \nInflammatory Demyelinating Poly -neuropathy, Chronic Urticaria, \nEncephalitis, Encephalopathy, Erythema Nodosum, Fibrom yalgia, \nGuillain -Barré Syndrome, Hearing Loss, Immune Thrombocytopenic \nPurpura, Infantile Spasms, Juvenile Idiopathic Arthritis, Multiple \nSclerosis, Neuromyelitis Optica, Optic Neuritis, Polyarteritis Nodosa, \nPsoriatic Arthritis, Reactive Arthritis, Rheumatoid Arthritis, Seizures, \nSmall Fiber Neuropathy, Stroke, Sudden Infant Death Syndrome, \nSystemic Lupus Erythematosus, Thrombocytopenia, Transverse \nMyelitis134 \n \nThis means that even among the 158 serious injuries that the CDC and HRSA (an agency which \ndefends against vaccine injury claims) identified as the most commonly claimed injuries from \n \n129 https://www.nap.edu/read/2138/chapter/2#12 .  \n130 https://www.nap.edu/read/2138/chapter/2#12 . \n131 https://www.nap.edu/read/2138/chapter/12 .  \n132 https://www.nap.edu/read/2138/chapter/12 . \n133 https://www.nap.edu/read/13164/chapter/2#3 .  \n134 https://www.nap.edu/read/13164/chapter/2#3 . \n20 \n vaccines, the CDC nor the greater scientific community have conducted the studies necessary to \nrule out vaccines as a cause for over 86% of these commonly claimed vaccine harms. 135 \n \nIn addition to these IOM reports, HHS has also relied upon what it has asserted is “ the most \ncomprehensive review ” of the literature on vaccine safety ever conducted —a 740 -page vaccine \nsafety report from 2014 by AHRQ —to claim that routine childhood vaccines are safe.136 \nThis 2014 report begins by identifying 20,478 studies as related or potentially related to vaccine \nsafety and excludes 20,312 of them for various reasons including that they did not address vaccine \nsafety, or had an unacceptable design.137 After this weeding out process, AHRQ was left with only \n166 studies it deemed relevant and potentially reliable for assessing vaccine safety, and only 97 of \nthose involved children.  \nHence, AHRQ, in what HHS said is “the most comprehensive review” of the literature on vaccine \nsafety, found there were only 97 studies ever conducted that it deemed potentially reliable to assess \nthe safety of childhood vaccines given to babies and childre n in the United States. This initial list \ndid not mean these 97 studies supported that one or more vaccines were safe, that was just the \ninitial universe of studies AHRQ said it identified to potentially  answer that question.  \nThese 97 studies were virtually all funded and/or authored (usually both) by a pharmaceutical \ncompany reviewing its own vaccine.138 AHRQ excluded all individual case reports (usually \ninstances of immediate and obvious vaccine injuries) despite the fact that practitioners can \ntypically afford to publish only in this form.139 It excluded all experimental studies which could \nexplain the biological mechanisms of how vaccines can cause injury or death, such as studies on \nhow vaccines or aluminum adjuvants can cause immune system dysregulation.140 It also excluded \nanimal studies which – because of ethical restrictions applicable to human research – often provide \nthe scientific evidence of how vaccines can cause harm.141 \nThe result is that this “comprehensive review” included only 97 studies that are applicable to \nchildren,142 77 of which were directly funded and/or authored (typically both) by the very pharma \ncompany whose vaccine(s) the study reviews.143 As for the remaining 20 studies, almost all were \n \n135 https://www.nap.edu/read/13164/chapter/2#3 . \n136 https://www.ncbi.nlm.nih.gov/books/NBK230053/ ; https://archive.org/details/hhs -response -1.  \n137 Id.  \n138 Id.  \n139 Id. \n140 Id. \n141 Id. (AHRQ also excluded studies using VAERS, one of the few resources available to study vaccine safety without \npharma type funding).  \n142 Excluding two studies it double counted.  \n143 https://www.ncbi.nlm.nih.gov/books/NBK230053/ . \n21 \n funded and/or authored by agencies and/or individuals that directly or indirectly receive funding \nfrom the pharma company whose vaccine(s) the study reviews.144 \nAHRQ then further cut down these 97 studies, explaining that comparing vaccinated (exposed) \nand unvaccinated (unexposed) children is critical for evaluating vaccine safety and asserts that \nonly 59 of these studies compared “vaccinated versus unvaccinated c hildren or adolescents.”145  \nAs for the 59 studies that AHRQ claims compared “vaccinated versus unvaccinated children or \nadolescents,” the following is a breakdown of these studies by vaccine type: rotavirus (34 studies), \nHPV (13 studies), influenza (6 studies), Hib (3 studies), menin gococcal (2 studies), and varicella \n(1 study). 146 Note that only 20 of these 59 studies involve an injected vaccine; the remainder \ninvolve rotavirus which is given orally and two of the influenza studies involve inhaled strains.147 \nHence , among these 59 studies, there are no studies for the following seven vaccines: Hep B, DTaP, \nPCV, IPV, MMR, Hep A, or Tdap. These seven vaccines constitute a majority of the routine \nchildhood vaccines, including four vaccines injected three times each in the first six months of \nlife—Hep B, DTaP, PCV, and IPV.  \nThis means that the “most comprehensive review” of the literature on vaccine safety, according to \nHHS, did not identify any study meeting its own criteria of reliability for a majority of the routine \nvaccines on CDC’s childhood schedule.  \nAs for the 59 studies AHRQ did identify for six different vaccines, AHRQ’s claim that they each \nhad an unvaccinated group is inaccurate . This is because in almost all the studies involving an \ninjected vaccine, the control group was vaccinated or injected with one or more active vaccine \ningredients.  \nFor example, in the three Hib studies that AHRQ labeled as “vaccinated versus unvaccinated \nchildren or adolescents,” the “control group” were all vaccinated. By way of example, one of these \nstudies reviewed the Hib -PHiD vaccine made by GSK in a study funde d by GSK and authored by \nGSK employees which, incidentally, is not a U.S. vaccine. It compared 199 infants who received \nHib-PHiD, DTPa, HBV, IPV, and Hib (the experimental group) with 101 infants who received \nDTPa, HBV, IPV, and Hib (the control group whic h AHRQ labeled “unvaccinated”).148 Labeling \nthis a “vaccinated versus unvaccinated” study is not accurate. It is noteworthy that approximately \n5% of infants in each group reported a serious adverse event, yet because  the rates were similar in \n \n144 Id.  \n145 Id.  \n146 Id.  \n147 The 34 rotavirus studies that AHRQ claims compare “vaccinated with unvaccinated children” compared children \nreceiving oral drops of rotavirus with children receiving oral drops of the following vaccine ingredients: Polysorbate 80, \nCitrate, Phosphate, Dext ran, Sorbitol, Amino acids, Dulbecco’s Modified Eagle Medium, Calcium Carbonate, and/or \nXanthan. See Chapter 10 . The two studies involving LAIV, an inhaled influenza vaccine, involved a pharma company \nreviewing its own product: one involved 20 immunocompromised children with cancer in which 10 received LAIV \nand 10 received a placebo, https://pubmed.ncbi.nlm.nih.gov/21496468/  (https://perma.cc/8MP9 -EHHT ), and the other \ncompared 261 children who received LAIV with 65 children who first received placebo and were then offered LAIV \nafter 28 days, https://pubmed.ncbi.nlm.nih.gov/21060780/  (https://perma.cc/7L2Y -PW9V ).  \n148 https://pubmed.ncbi.nlm.nih.gov/23432812/  (https://perma.cc/7HDW -4XFY ).  \n22 \n each group, the vaccine was deemed “safe” by the GSK employees studying a GSK vaccine in a \nGSK -funded study.149 \nUsing one final example, in all 13 studies involving HPV vaccine that AHRQ labels “vaccinated \nversus unvaccinated adolescents,” the “unvaccinated” group either received a vaccine or an \ninjection of an adjuvant in the HPV vaccine, AAHS (save one study in which 17 girls apparently \nreceived nothing).150 HPV vaccines were studied in adolescent s and older women who, unlike \nchildren or babies, can articulate if they are experiencing a serious adverse reaction, such as \nneurological issues. In most of these studies, the rate of serious adverse event reports in both groups \n(the vaccinated group and the fake “unvaccinated” group) were , in some instances , in the  double \ndigits . The vaccine was deemed “safe” in these GSK - or Merck -funded studies using their own \nemployees reviewing their own vaccine because the rate of harm was similar in both groups.151 \nFor context, and reflecting a bias that may have driven this review, AHRQ’s “comprehensive \nreview” began by expressing concern that “vaccination rates remain well below established \nHealthy People 2020 targets for many vaccines” and that “[i]ncreasing vaccination rates remains \ncritically important.”152 It laments that “public concerns about vaccine safety continue to persist” \ndespite “the rigorous processes new vaccines must undergo before receiving approval” and that \nthey meet “stringent criteria for safety.”153 It is unclear whether the authors of this review reviewed  \nthe clinical trials relied upon to license childhood vaccines.  \nIt is also noteworthy that, despite only accepting a limited number of studies as reliable, it did find \nsupport for one or more childhood vaccines causing: febrile seizures, arthralgia, thrombocytopenic \npurpura, meningitis , and encephalitis.154  \n  \nSLIDES 39 -44: INJURY CLAIMED TO HAVE BEEN MOST THOROUGLY STUDIED  \nThese slides discuss autism  because  is it is the adverse event claimed to have been the most \nthoroughly studied in relation to vaccines and hence provides a good indication of how well other \nadverse events have been studied.  \n \nWhile autism was relatively uncommon in the early 1980s, it was a serious enough concern that in \nthe 1986 Act, Congress required that the federal health authorities review the scientific literature \nregarding whether there is a connection between pertussis -containing vaccines and autism. As \nprovided in the 1986 Act: “the Secretary of Health and Human Services shall complete a review \nof all relevant medical and scientific information … on the nature, circumstances, and extent of \n \n149 https://pubmed.ncbi.nlm.nih.gov/23432812/  (https://perma.cc/7HDW -4XFY ); https://www.icandecide.org/wp -\ncontent/uploads/ 2019/09/ICAN -Reply -1.pdf  at pp. 36 -42 (https://perma.cc/LX4V -LDVP ).  \n150 https://www.icandecide.org/wp -content/uploads/ 2019/09/ICAN -Reply -1.pdf  at pp. 36 -42 (https://perma.cc/LX4V\n-LDVP ). \n151 Id. \n152 Id. \n153 Id.  \n154 Id.  \n23 \n the relationship, if any, between vaccines containing pertussis (including whole cell, extracts, and \nspecific antigens) and … Autism.”155  \n \nHHS in turn commissioned the IOM to conduct this review. When that review was published in \n1991, the IOM explained that it could not identify any study to support the claim that pertussis \nvaccines do not cause autism. As explained by the IOM: “No data were  identified that address the \nquestion of a relation between vaccination with DPT or its pertussis component and autism.”156 \n \nThe IOM committee included the following warning in its 1991 report:  \n \nIn the course of its review, the committee found many gaps and \nlimitations in knowledge bearing directly and indirectly on the \nsafety of vaccines.  … If research capacity and accomplishment in \nthis field are not improved, future reviews of vaccine safety will be \nsimilarly handicapped.157 \n \nTwo decades later, in 2012, the IOM issued another report on vaccine safety, this time \ncommissioned by the CDC and HRSA, which again assess ed the evidence bearing on whether \npertussis vaccines, including DTaP, cause autism. It did so because, according to HRSA, autism \nremained one of the most commonly claimed injuries from this vaccine.158 This time, the request \nto the IOM also included reviewing whether tetanus and diphtheria vaccines can cause autism.  \n \nThe IOM again convened a committee composed of individuals with expertise in pediatrics, \ninternal medicine, neurology, immunology, immunotoxicology, neurobiology, rheumatology, \nepidemiology, biostatistics, and law to answer th ese question s.159  \n \nAs in 1991, the IOM again was unable to locate a study supporting the claim that DTaP does not \ncause autism. The IOM concluded in its 2012 report: “The evidence is inadequate to accept or \nreject a causal relationship between diphtheria toxoid –, tetanus tox oid–, or acellular pertussis –\ncontaining vaccine and autism.”160 \n \nThe following is the IOM’s full explanation for this finding in its 2012 report:  \n \nAUTISM  \nEpidemiologic Evidence  \nThe committee reviewed one study to evaluate the risk of autism \nafter the administration of DTaP vaccine. This one study (Geier and \nGeier, 2004) was not considered in the weight of epidemiologic \n \n155 https://nap.nationalacademies.org/read/12796/chapter/12#268 .  \n156 https://www.nap.edu/read/1815/chapter/1#v . \n157 https://www.nap.edu/read/1815/chapter/9 . \n158 https://www.nap.edu/read/13164/chapter/2#2 . \n159 https://www.nap.edu/read/13164/chapter/1#v .  \n160 https://www.nap.edu/read/13164/chapter/12#545 . \n24 \n evidence because it provided data from a passive surveillance \nsystem and lacked an unvaccinated comparison population.  \nWeight of Epidemiologic Evidence  \nThe epidemiologic evidence is insufficient or absent to assess an \nassociation between diphtheria toxoid -, tetanus toxoid -, or acellular \npertussis -containing vaccine and autism.  \n \nMechanistic Evidence  \nThe committee did not identify literature reporting clinical, \ndiagnostic, or experimental evidence of autism after the \nadministration of vaccines containing diphtheria toxoid, tetanus \ntoxoid, and acellular pertussis antigens alone or in combination.  \nWeight of Mechanistic Evidence  \nThe committee assesses the mechanistic evidence regarding an \nassociation between diphtheria toxoid -, tetanus toxoid -, or acellular \npertussis -containing vaccine and autism as lacking.  \n \nCausality Conclusion  \nConclusion 10.6:  The evidence is inadequate to accept or reject a \ncausal relationship between diphtheria toxoid -, tetanus toxoid -, or \nacellular pertussis -containing vaccine and autism.           \nThe single study the IOM could locate regarding whether DTaP causes autism (Geier and Geier, \n2004) concluded that there was an association between DTaP and autism.161 The IOM gave this \nstudy no weight because it was based on VAERS reports.  \n \nThe 2012 report from the IOM also looked at whether MMR vaccine, recommended for routine \nadministration after one year of age, can cause autism.162 The IOM identified 22 studies that \nevaluated the connection between MMR vaccine and autism, but did not rely on 17 of them due to \nlack of “unvaccinated comparison population,” “individual -level data,” or “methodological \nlimitations.” 163 Based on the remaining five studies, none of which involved  children in the United \nStates, the IOM concluded that, “The evidence favors rejection of a causal relationship between \nMMR vaccine and autism.” 164 This conclusion reflects that studies can be conducted which the \nIOM is willing to rely upon to reach a conclusion that a particular vaccine does not cause autism. \nThat said, the IOM’s conclusion regarding MMR vaccine and autism does not support the much \nbroader claim that “vaccines do not cause autism,” as it only addresses whether the MMR vaccine \n \n161 https://www.nap.edu/read/13164/chapter/12?term=autism#545 . \n162 https://nap.nationalacademies.org/read/13164/chapter/6#145 . \n163 https://nap.nationalacademies.org/read/13164/chapter/6#145 . \n164 https://nap.nationalacademies.org/read/13164/chapter/6#145 . \n25 \n can cause autism . It does not address  whether any other vaccines, especially those given to infants, \ncan cause autism.165 \n \nTwo years later, in 2014, the AHRQ conducted a review which again included looked at any study \nregarding pertussis, tetanus, and diphtheria vaccines, including DTaP, and autism.166 HHS has \nexplained in 2018 that this report represented “the most comprehensive review to date of published \nstudies on the safety of routine vaccines recommended for children in the United States.”167 As \nwith the IOM reports from 1991 and 2012, the “comprehensive review” published by AHRQ in \n2014 again concluded that it could not identify a study to support the claim that DTaP, \nadministered at 2, 4, and 6 months of age, does not cause autism.168 \n \nAHRQ also reviewed autism and Hep B vaccine, administered at 1 day, 1 month, and 6 months of \nage, and did not identify a study to support the claim that this vaccine does not  cause autism.169 \nInstead, the only study meeting AHRQ’s criteria for reliability was from the Stony Brook \nUniversity Medical Center which found a 300% increased rate of autism among newborns \nreceiving a Hep B vaccine at birth compared to those who did not get this vaccine  at birth. AHRQ’s \n2014 review summarizes the results of this study as follows:  \n \nResult was significant for the risk of autism in children who received \ntheir first dose of Hepatitis B vaccine during the first month of life \n(OR 3.00, 95% CI 1.11, 8.13), compared with those who received \nthe vaccination after the first month of life or no t at all.170 \n  \nAHRQ therefore identified one study that showed an association, and no studies to support that \nHep B vaccine does not cause autism; its conclusion was that it does not know whether the Hep B \nvaccine causes autism.171  \n \nA subsequent October 12, 2017 letter sent to HHS and signed by Robert F. Kennedy Jr. and others \nexplained that there are no published studies supporting that the vaccines given in the first year of \nlife do not cause autism. The letter asked HHS to “ identify the specific studies on which HHS \nbases its blanket claim that no vaccines cause autism.”172 The letter also cited to studies which did \nfind an association between one or more of these vaccines and autism and provided scientific \nsupport and letters from world -leading aluminum scientists on how this particular vaccine \ningredient could cause autism.173 \n \n \n165 https://nap.nationalacademies.org/read/13164/chapter/6#145 . \n166 https://www.ncbi.nlm.nih.gov/books/NBK230053/pdf/Bookshelf_NBK230053.pdf . \n167 https://archive.org/details/hhs -response -1.  \n168 https://www.ncbi.nlm.nih.gov/books/NBK230053/pdf/Bookshelf_NBK230053.pdf . \n169 Id. \n170 Id. \n171 Id. \n172 https://archive.org/details/ican -hhs-notice -1 at 13 .  \n173 Id. \n26 \n On January 18, 2018, HHS  sent a response which provided various links to CDC webpages but \nneither those links nor the content of those webpages identified  a study which supports the claim \nthat the vaccines given to infants  do not cause autism.174 This was explained in a follow -up letter \nto HHS which again requested any supporting studies and again reiterated the data regarding how \naluminum adjuvants can cause autism.175 It also specifically asked HHS the following:  \n \nThe following white paper provides the peer reviewed scientific \nsupport for how aluminum adjuvants injected into the body travel to \nthe brain, can cause IL -6 production and microglial activation in the \nbrain, and that this in turn can cause autism: http:// icandecide.\norg/white -papers/ ICAN -Aluminum Adjuvant -Autism.pdf. Please \nclearly and specifically explain which steps in this chain of \ncausation or any other aspect of this white paper HHS disputes.176 \n \nNo response from HHS was ever provided to rebut these studies or scientific findings.177 \n \nOn December 31, 2019, the CDC was sued in federal court for failing to provide studies in response \nto a Freedom of Information Act request submitted to the CDC seeking studies it relied upon to \nsupport that the vaccines the CDC recommends be given in the f irst year of life —DTaP, Hep B, \nHib, PCV13, and IPV, individually and collectively —do not cause autism.178  \n \nTo resolve the lawsuit, the CDC provided a list of the 16 studies and 4 reviews it claimed support \nthe claim that the foregoing vaccines do not cause autism. This list was memorialized in a signed \nstipulation with the CDC on February 28, 2020, and then ent ered as an order of the Court on March \n2, 2020.179 The stipulation and order provided in relevant part as follows:180 \n \nWHEREAS, the Institute for Autism Science and Informed \nConsent Action Network (“ICAN”) commenced the above -\ncaptioned lawsuit against the Centers for Disease Control and \nPrevention (“CDC”) regarding six  Freedom of Information Act \nrequests (the  “FOIA Requests ”); \n \nWHEREAS,  the FOIA  Requests  were  as follows:  \n \n• “All studies  relied  upon  by CDC  to claim  that the \n \n174 https://archive.org/details/hhs -response -1.  \n175 https://archive.org/details/ican -reply -1.  \n176 Id at 83 .  \n177 https://archive.org/details/ican -follow -up-final.  \n178 https://ecf.nysd.uscourts.gov/doc1/127026118709  (https://www.courtlistener.com/docket/16644712/1/institute -\nfor-autism -science -v-centers -for-disease -control -and-prevention/ ); https://ecf.nysd.uscourts.gov/doc1/127126484251 . \n179 https://ecf.nysd.uscourts.gov/doc1/127126484251  (https://www.courtlistener.com/docket/16644712/15/institute -\nfor-autism -science -v-centers -for-disease -control -and-prevention/ ). \n180 https://ecf.nysd.uscourts.gov/doc1/127126484251  (https://www.courtlistener.com/docket/16644712/15/institute -\nfor-autism -science -v-centers -for-disease -control -and-prevention/ ). \n27 \n DTaP  vaccine  does not cause autism.”  \n• “All studies relied upon by CDC to claim that neither \nEngerix -B nor Recombivax HB do not cause \nautism.”  \n• “All studies relied upon by  CDC  to claim  that \nPrevnar 13  does not cause autism.”  \n• “All studies relied  upon by  CDC  to claim  that Hib \nvaccines do not cause autism.”  \n• “All studies relied upon by CDC to claim that \ninactivated polio vaccine (‘IPV’) does not cause \nautism.”  \n• “Copies of the studies the CDC relies upon to claim \nthat the cumulative exposure of vaccines it \nrecommends that babies be administered  during  the \nfirst six months  of life do not cause  autism.”  \n \nWHEREAS,  after conducting  a search  of its records, the \nCDC identified  the following studies responsive to the FOIA \nRequests:  \n \n1. Madsen  KM, Hviid A, Vestergaard M,  Schendel D,  \nWohlfahrt J,  et al. A population -based study of  measles,  \nmumps,  and rubella  vaccination  and autism.  N Engl  J Med.  \n2002;347  (19): 1477-1482.  \n2. IOM  (Institute  of Medicine).  2012.  Adverse  Effects  of \nVaccines:  Evidence  and Causality. Washington, DC: The  \nNational Academies Press.  \n3. IOM (Institute of Medicine). 2004. Immunization Safety \nReview: Vaccines and Autism. Washington, DC: The \nNational Academies Press.  \n4. IOM  (Institute  of Medicine).  2013.  The childhood \nimmunization  schedule and  safety: Stakeholder concerns,  \nscientific  evidence, and  future  studies.  Washington, DC:  The \nNational  Academies Press.  \n5. Frombonne E, Zakarian R, Bennett A, et al. Pervasive \ndevelopmental disorders in Montreal, Quebec, Canada: \nprevalence and links  with immunizations.  Pediatrics. \n2006;118(1):el39 -50. \n6. Taylor LE, Swerdfeger AL,  Eslick GD. Vaccines are not \nassociated with autism: An evidence­ based meta -analysis of  \ncase-control and  coh01t  studies.  Vaccine.  2014;32:3623 -\n3629.  \n7. Ball L, Ball R, Pratt RD. An assessment of thimerosal in \nchildhood vaccines. Pediatrics. 2001;107:1147 -1154.  \n8. Hviid  A, Stellfeld  M, Wohlfahrt J,  Melbye  M. Association  \nbetween thimerosal -containing  vaccine and autism. JAMA. \n2003;290:1763 -6. \n28 \n 9. Madsen  KM, Lauritsen  MB, Pedersen  CB, et al. Thimerosal  \nand the occurrence  of autism:  negative ecological evidence  \nfrom Danish population -based data.  Pediatrics.  2003;112(3 \nPt 1):604 -6. \n10. Stehr -Green P, Tull P, Stellfeld M, et al. Autism and \nthimerosal -containing vaccines: lack of consistent evidence \nfor an association. Am JPrev Med. 2003;25(2):101 -6. \n11. Verstraeten T, Davis RL, Destefano F, et al. Safety of \nthimerosal -containing vaccines: a two­ phased study of \ncomputerized health maintenance organization databases. \nPediatrics. 2003;112(5):1039 -48. \n12. Andrews  N, Miller  E, Grant  A, et al. Thimerosal  exposure  in \ninfants  and developmental  disorders: a retrospective cohort \nstudy in the United Kingdom does not supp01t a causal \nassociation. Pediatrics. 2004;114(3):584 -91. \n13. Thompson WW, Price C, Goodson B, et al.  Early thimerosal \nexposure and neuropsychological outcomes  at 7 to 10 years. \nN Engl JMed. 2007;357(13):1281 -92. \n14. McMahon  AW,  Iskander  Il(, Haber  P, Braun  MM,  Ball R. \nInactivated influenza  vaccine (IIV) in children  <2 years  of \nage: Examination  of selected  adverse  events  reported  to the \nVaccine  Adverse Event Reporting System (VAERS) after \nthimerosal -free or thimerosal -containing vaccine. Vaccine. \n2008 Jan; 26(3):427 -429. \n15. Schechter R, Grether Il(.  Continuing increases in autism \nreported to California's developmental services system:  \nMercury in retrograde. Arch Gen  Psychiatry. 2008;65:19 -24. \n16. DeStefano F.  Thimerosal -containing  vaccines: evidence \nversus public apprehension. Expe1t Opin Drug Saf. \n2009;8(1):1 -4. \n17. Tozzi AE, Bisiacchi P, Tarantino V, et al. \nNeuropsychological performance 10 years after \nimmunization in infancy with  thimerosal -containing  \nvaccines. Pediatrics. 2009;123(2):475 -482. \n18. Price CS, Thompson WW, Goodson B, et al. Prenatal and \ninfant exposure to thimerosal from vaccines and \nimmunoglobulins  and risk  of autism.  Pediatrics. \n2010;126(4):656 -64. \n19. Barile JP, Kuperminc GP, Weintraub ES, et al. Thimerosal \nexposure in early life and neuropsychological outcomes 7 -\n10 years  later.  J Pediatr  Psychol. 2012;37(1):106 -18. \n20. Destefano F,  Price CS, Weintraub ES.  Increasing exposure \nto antibody -stimulating  proteins and polysaccharides in  \nvaccines is  not associated with risk  of autism. J  Pediatr. \n2013;163(2):561 -7. \n \n29 \n None of these 20 studies /reviews identified by the CDC included a study to support the claim that \nthe vaccines on the CDC’s childhood vaccine schedule given to infants —DTaP, Hep B, Hib, \nPCV13, and IPV —do not cause autism. Instead, these 20 studies /reviews include:  \n \n• 15 studies and 3 reviews concerning MMR and/or thimerosal;  \n• 1 study concerning antigen (not vaccine) exposure; and  \n• 1 review concerning MMR, thimerosal, and DTaP.  \nHence, only one of the 20 studies /reviews identified by the CDC involved a vaccine given to \ninfants, DTaP. This was the review the IOM published in 2012, discussed above, which failed to \nidentify a study to support that DTaP does not cause autism. Instead, it found only one study \nregarding DTaP vaccine and autism, and that study found an association between this vaccine and \nautism. Hence, the only study or review out of 20 identi fied by the CDC that reviewed a vaccine \ngiven during the first year of life was a study which did find  an associa tion between DTaP vaccine \nand autism.  \n \nOn August 25, 2020, the head of CDC’s Clinical Immunization Safety Assessment (CISA) Project, \none of the four vaccine safety systems listed on the CDC’s website, was questioned under oath in \na case specifically about autism and vaccines . She also confirmed that there are no studies to \nsupport that infant vaccines do not cause autism : \n \nQ: [A]ccording to your profile, you have done most of the clinical trials relied upon \nto license many of the vaccines, correct, on the market?   \nA: Yes, sir.   \nQ: Okay. So you’re highly experienced at conducting clinical trials; correct?   \nA: I am highly experienced conducting clinical trials.   \nQ: ... And you’re familiar with many of the clinical trials that -- relied upon to \nlicense many of the vaccines currently on the market; correct?   \nA: I am.   \nQ: Okay. In your opinion, did the clinical trials relied upon to license the vaccines \nthat [the child] received, many of which are still on the market today, were they \ndesigned to rule out that the vaccine causes autism?   \nA: No. …  \nQ: [I]n the expert disclosures for this case, it asserts that among other things you \nwill testify that, quote, the issue of whether vaccines cause autism has been \nthoroughly researched and rejected, end quote. …  \nQ: … It’s your testimony that MMR vaccine cannot cause autism?   \nA: That’s correct.   \nQ: It’s your testimony the HepB vaccine cannot cause autism?   \nA: That’s correct.   \nQ: It’s your testimony that IPOL cannot cause autism?   \nA: Yes.   \nQ: It’s your testimony that Hib vaccine cannot cause autism?   \nA: Yes.   \nQ: It’s your testimony that varicella vaccine cannot cause autism?   \nA: Yes.   \nQ: It’s your testimony that Prevnar vaccine cannot cause autism?   \n30 \n A: Yes.   \nQ: And it’s your testimony that DTaP vaccine cannot cause autism?   \nA: Yes.  … \nQ: And do you have a study that supports that DTaP doesn’t cause autism?   \nA: I have -- I do not have a study that -- that DTaP causes autism, so I don’t have \neither.   \nQ: … Do you have any study one way or another of whether IPOL causes autism?   \nA: No, I do not, sir.   \nQ: Do you have any study one way or another of whether Engerix -B causes autism?   \nA: I do not have any evidence that it causes autism, nor that it does not.   \nQ: And what about HibTITERs vaccine, any evidence one way or another of \nwhether it causes autism?   \nA: No.  … \nQ: … And what about Prevnar vaccine? Any evidence, one way or another?   \nA: No, sir. No, sir.  … \nQ: … And how about varicella vaccines … are there any studies one way or another \nthat support whether it does or doesn’t cause autism?   \nA: [As p]art of MMR, but not as varicella by itself, no sir. No studies that say it \ndoes or no studies that say it doesn’t.   \nQ: … There have been studies that have found an association between hepatitis B \nvaccine and autism; correct?   \nA: Not studies that I feel are credible.   \nQ: Okay. Which study -- which study … are you referring to when you say that?   \nA: Well, why don’t you show me the study and then I’ll say whether I agree with \nit.181  \n \nAs the foregoing reflects, and as explained by the Secretary of Health and Human Services, Robert \nF. Kennedy Jr., the CDC cannot claim that vaccines given in the first year of life do not cause \nautism. It cannot do so because the studies to disprove that t he vaccines given to infants do not \ncause autism have not been conducted.  \n \nThe need for studies regarding whether these vaccines have contributed to the autism epidemic is \nacute. Since the 1980s, the rise in cases of autism has occurred in lockstep across all geographic \nareas of the United States and across all racial, ethnic, an d religious groups .182 \n \nGiven the steep rise, the cause of autism is an environmental change that has occurred throughout \nthe United States since the early 1980s. A study published in Environmental Health  out of the \nUniversity of Colorado reviewed the correlations between numerous environmental factors \nsuspected of potentially causing autism and the change in the level of their exposure during \nchildhood since the 1980.183 The environmental exposure in the study showing the highest \n \n181 https://archive.org/details/kathryn -edwards -full-pdf-transcript .  \n182 See The CDC’s Autism and Developmental Disabilities Monitoring (ADDM) Network, https://www.cdc. gov/\nncbddd/autism/addm.html , the U.S. Department of Education data collected pursuant to the Individuals with \nDisabilities Act (IDEA),  https://sites.ed.gov/idea/data/ , and the California Department of Developmental Services \n(CDDS), https://www.dds.ca.gov/transparency/autism/ . \n183 https://pubmed.ncbi.nlm.nih.gov/25189402/ .  \n31 \n statistical correlation with autism rates was the increasing doses of vaccination. The following \ncharts are from this study. The circles represent the number of vaccine doses and the triangles \nrepresents the rate of autism:  \n \n \nFigure S8. Temporal trend in autism compared to temporal trend in \ncumulative number of immunizations administered to U.S. infants \nand toddlers by 2, 6, 12 and 18 months via immunization according \nto the CDC recommended schedule.184 \n \nCorrelation does not equal causation, but it does provide a safety signal that merits investigation, \nincluding because numerous studies support immune dysfunction as a cause of autism and vaccines \nare intended to and do systemically modify the immune syste m. Additionally, a significant \nproportion of parents of children with autism identify vaccines as what they believe caused their \nchild’s autism, including pointing to the vaccines given in the first six months of life.185  \n \nSLIDE 45:  ADVERSE REACTIONS MANUFACTURERS HAVE A BASIS  \nTO BELIEVE ARE CAUSALLY RELATED  \nPharmaceutical companies have access to internal vaccine safety data that is unavailable to public \nhealth agencies and the public.  \n \nFederal law requires pharmaceutical companies to disclose, in the package insert for each vaccine, \n“only those adverse events for which there is some basis to believe there is a  causal \nrelationship  between the drug and the occurrence of the adverse event .”186 With access to safety \ndata that is unavailable to the public or to health authorities, the pharmaceutical companies are \nable to identify what injuries may be caused by vaccines that committees within HHS, CDC, IOM, \nand AHRQ cannot do without access to such data.  \n \n184 https://pubmed.ncbi.nlm.nih.gov/25189402/ . \n185 https://www.ncbi.nlm.nih.gov/pubmed/16685182 ; https://www.ncbi.nlm.nih.gov/pubmed/25398603 ; https://www.\nncbi. nlm.nih.gov/pubmed/ 16547798 ; https://www.ncbi.nlm. nih.gov/pmc/articles/PMC1448378/ . \n186 https://www.ecfr.gov/current/title -21/chapter -I/subchapter -C/part -201.  \n\n32 \n  \nThese adverse events identified by pharmaceutical companies are typically listed in Section 6.2 of \neach vaccine’s package insert. Only adverse events for which these companies have a basis to \nbelieve have a “causal relationship” with the vaccine are to be listed pursuant to federal law. \nAdverse events for which there is only a correlation with the administration of the vaccine should \ntherefore not be listed.  \n \nMany of the chronic diseases that have risen over the prior decades are disclosed on one or more \nvaccine package inserts.187  \n \nSLIDES 46 -48, 50: STUDYING UNEXPOSED GROUPS  \nProperly assessing the safety of a product typically requires comparing an exposed group to an \nunexposed group and assessing their health outcomes, i.e., comparing a group that receives the \nproduct with a group that does not receive the product. Regarding vaccines, that requires \ncomparing the health outcomes between vaccinated (one or more vaccines) and unvaccinated ( no \nvaccines) children. This can be accomplished by using existing databases that contain this health \ndata.  \n \nIn 2013, the IOM published a report after having been commissioned by HHS to review the overall \nsafety of the CDC childhood schedule “to identify health outcomes associated with some aspect \nof the childhood immunization schedule,” including “asthma, autoimmunity, autism, other \nneurodevelopmental disorders (e.g., learning disabiliti es, tics, behavioral disorders, and \nintellectual disability), seizures, and epilepsy.”188 This was a different IOM report than the ones \npreviously discussed above as it did not focus on individual vaccines but rather on the safety of \nthe CDC childhood vaccine schedule as a whole.   \n \nThe IOM found that no studies had ever been conducted which compared the health outcomes of \nchildren receiving the CDC’s childhood vaccine schedule with children that had not been \nvaccinated:  \n \n[F]ew studies have comprehensively assessed the association \nbetween the entire immunization schedule or variations in the \noverall schedule and categories of health outcomes, and no study … \ncompared the differences in health outcomes … between entirely \nunim munized populations of children and fully immunized children. \nExperts who addressed the committee pointed not to a body of \nevidence that had been overlooked but rather to the fact that existing \nresearch has not been designed to test the entire immunization  \nschedule. …  \n \n \n187 https://www.fda.gov/vaccines -blood -biologics/vaccines/vaccines -licensed -use-united -states . \n188 https://www.nap.edu/read/13563/chapter/2#5 . \n33 \n [Also,] studies designed to examine the long -term effects of the \ncumulative number of vaccines or other aspects of the immunization \nschedule have not been conducted.189 \n \nWhen the IOM committee expanded its search for any evidence that could help it assess the safety \nof the CDC’s childhood vaccine schedule, it stated that it “found a paucity of information, \nscientific or otherwise, that addressed the risk of adverse events in  association with the complete \nrecommended immunization schedule.”190 The IOM  found:  “There is no evidence that the \nschedule is not safe.”191  \n \nThe IOM’s report from 2013 did assert that it “is possible to make this comparison [between \nvaccinated and unvaccinated children] through analyses of patient information contained in large \ndatabases such as VSD [the Vaccine Safety Datalink].”192 Subsequently, the CDC commissioned \na 64-page white paper, published in April 2016, that discussed how to conduct such studies using \nthe VSD .193 But no such study has even been published by the CDC despite the fact this white \npaper acknowledges that many chronic disorders children are experiencing today in epidemic \nnumbers are biologically plausible outcomes from exposure to CDC’s childhood vaccin e schedule \nbut have not yet been properly studied. 194 \n \nWhile CDC and pharmaceutical -funded scientists have never published such a study, a few such \nstudies have been published.  \n \nA pilot study, based on parental surveys of homeschool children, from the School of Public Health \nat Jackson State University, published in 2017, found that 33% of vaccinated preterm babies had \na neurodevelopmental disorder while 0% of the unvaccinated pre term babies had a \nneurodevelopmental disorder;195 and another study by the same group found that vaccinated \nchildren, compared to unvaccinated children (receiving no vaccines), had a 74% decreased risk of \nchicken pox and a 70% decreased risk of pertussis, but had an increased risk of 290% for allergies, \n320% for ADHD, 320% for autism, 190% for eczema, 420% for learning disabilities, and 270% \nfor any neuro -developmental delay.196 \n \nIn another study aggregating data from three medical practices in the United States, the health \noutcomes of vaccinated and unvaccinated children born between 2005 and 2015 were compared; \nthis study found that vaccinated children, compared to unvaccinated c hildren, had a statistically \n \n189 https://www.nap.edu/read/13563/chapter/2#5 . \n190 https://www.nap.edu/read/13563/chapter/6?term=paucity#70 . \n191 https://www.nap.edu/read/13563/chapter/2#12 . \n192 https://www.nap.edu/read/13563/chapter/2#13 . \n193 https://www.cdc.gov/vaccine -safety/media/pdfs/white -paper -safety -508.pdf?CDC_AAref_Val=https://www.cdc.\ngov/vaccinesafety/pdf/WhitePaperSafety_WEB.pdf .  \n194 Id. \n195 https://www.oatext.com/pdf/JTS -3-187.pdf . \n196 https://www.oatext.com/pdf/JTS -3-186.pdf . \n34 \n significant increased rate of 118% for developmental delay, 349% for asthma, and 113% for ear \ninfections.197   \n \nResearchers at State University of New York at Stony Brook  have authored two studies  concerning \nthe hepatitis  B vaccine. One of those study’s f indings  were that male neonates vaccinated with the \nhepatitis B vaccine had a 3 times risk (OR=3.002, 95% CI 1.109 -8.126) for parental report of \nautism diagnosis compared to boys not vaccinated as neonates during that same time period .198 \nThe second study found that the odds of receiving early intervention or special education services \nwere 8.63 times as great (OR=8.63, 95% CI 3.24 –22.98) for vaccinated boys as for unvaccinated \nboys after adjustment for confounders.199 \n \nAdditional  unpublished data, including from the Amish community, reflects similar findings.200 \n \nSLIDE 49: CDC SURVEILLANCE SYSTEMS  \nVAERS  \n \nThe Vaccine Adverse Events Reporting System ( VAERS ) is jointly administered by the CDC and \nthe FDA. It is a passive reporting system to which anyone can submit reports of an injury after \nvaccination. However, the vast majority of reports are submitted by pharmaceutical companies, \nhealth care providers, an d state immunization programs.201  \n \nThe CDC explains that VAERS cannot establish causation between a vaccine and an injury and \nthat, at best, it can be used for signal detection. Hence, CDC explains that it should not be used to \nreach a causality conclusion regarding a claimed injury from on e or more vaccines. But it can \nprovide potential signals of vaccine harm based on the volume and type of reports received.  \n \nFrom 2013 and 2018, VAERS received 261,294 reports of adverse vaccine events, including 2,081 \ndeaths, 5,477 permanent disabilities, and 20,778 hospitalizations.202  \n \nA study of VAERS reporting commissioned by the AHRQ stated that “fewer than 1% of vaccine \nadverse events are reported.”203 In this study, AHRQ provided a $1 million grant to create a \nsoftware program at Harvard Pilgrim Health Care that would automate reporting injuries after \n \n197 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7268563/ .  \n198 https://pubmed.ncbi.nlm.nih.gov/21058170/ .  \n199 https://doi.org/10.1080/02772240701806501 . \n200 https://www.sirillp.com/wp -content/uploads/2025/01/Ex -D-Dr-Neuenschwander -Declaration -signed -w-exs.pdf ; \nhttp://sirillp.com/Letters -to-NY-DOH . \n201 https://web.archive.org/web/20150615195821/http://vaers.hhs.gov/about/faqs .  \n202 https://wonder.cdc.gov/vaers.html .  \n203 https://healthit.ahrq.gov/sites/default/files/docs/publication/r18hs017045 -lazarus -final-report -2011.pdf .  \n35 \n vaccination to VAERS.204 The result was the successful creation of a system at Harvard Pilgrim \nwhich automatically created adverse vaccine event reports:  \n \nPreliminary data were collected from June 2006 through October 2009 on 715,000 patients, and \n1.4 million doses were given to 376,452 individuals. Of these doses, 35,570 possible reactions \nwere identified.205 \n \nRegrettably, the CDC did not cooperate with making this new program functional. After creating \na software program that automatically created VAERS reports, the system’s developers asked the \nCDC to take the final step of linking VAERS with the Harvard Pilgr im system so that these reports \ncould be automatically transmitted into VAERS .206 But as the Harvard researchers explained:  \n \nUnfortunately, there was never an opportunity to perform system \nperformance assessments because the necessary CDC contacts were \nno longer available and the CDC consultants responsible for \nreceiving data were no longer responsive to our multiple requests to  \nproceed with testing and evaluation.207 \n \nVAERS cannot be used to determine whether a vaccine causes a harm because, while VAERS can \nprovide the number of people harmed (numerator), it cannot provide the total number of people \nvaccinated (denominator) from which to calculate a rate of harm. Automa ting VAERS reports \nfrom a fixed pool of people would have made calculating a rate and thus reaching a causality \nconclusion on a given harm possible. That type of automation has still not been implemented for \nVAERS.  \n \nIt is also noted that on December 4, 2020, before the first COVID -19 vaccine was rolled out, CDC \nreleased the VAERS Standard Operating Procedures for COVID -19 (“VAERS SOP”), which \nstated in relevant part:  \n \nThe analyses for COVID -19 vaccine safety signals will focus on \nidentifying deviations from preliminary safety data, and possibly \nfrom other vaccines, using disproportionality analyses and \ncomparisons of reporting rates.  \n \nTwo main approaches to data mining are Proportional Reporting \nRatios (PRRs) and Empirical Bayesian Geometric Means. Both \nhave published literature suggesting criteria for detecting “signals”. \nPRR will be used at CDC for potential signal detection; Empirica l \nBayesian data mining will be performed by FDA .208 \n \n \n204 Id. \n205 Id. \n206 Id. \n207 https://healthit.ahrq.gov/sites/default/files/docs/publication/r18hs017045 -lazarus -final-report -2011.pdf . \n208 https://www.cdc.gov/vaccinesafety/pdf/VAERS -COVID19 -SOP-4-Dec-2020 -508.pdf .  \n36 \n This SOP thus explained that CDC planned to conduct safety signal monitoring using Proportional \nReporting Ratios (“PRR”) and FDA planned to conduct safety signal monitoring using Empirical \nBayesian (“EB”) data mining.  \n \nOur firm requested the PRR signal detection data from CDC through FOIA and was denied. In the \ndenial letter, CDC stated that it had not conducted PRR analyses; it instead highlighted the \nsuperiority of and historical use of EB data mining, calling it the “ gold standard” and the “superior \nmethod” with which to detect safety signals. However, on September 2, 2022, then -CDC Director \nRochelle Walensky sent a letter to Senator Ron Johnson acknowledging that PRR had in fact been \nused: “CDC performed PRR analysis between March 25, 2022, through July 31, 2022, to \ncorroborate the results of EB data mining. Notably, results from PRR analysis were generally \nconsistent with EB data mining, revealing no additional unexpected safety signals.” Our firm then \nsued CDC based on this admission and ultimately received 51 excel files containing PRR data. 209 \nThese files showed that CDC’s own threshold for triggering a signal for adverse events was met \nfor numerous serious adverse events, including as seen in the following CDC tables noting that \nCDC had set anything above a “2” in the PRR row as a safety signal :210 \n \n \n209 https://www.sirillp.com/wp -content/uploads/2024/06/Response -to-FDA -Stay-b390d697ad6bc29544ff90e60795\n7c03.pdf .  \n210 https://icandecide.org/cdc -proportional -reporting -ratio/  (all PRR data is available for download at this site).  \n37 \n  \n \nWhen the CDC was asked about  the above data, it advised Senator Johnson that it was no longer \nrelying upon PRR and instead would only rely upon FDA’s EB data mining; as the then CDC \nDirector wrote to Senator Johnson:  \n \nN>=3 (Current Week), PRR>=2.00 (Ratio of \nMedDRA Codes\nALL Reports (18+)12/14/2020-\n05/06/2022\nCOVID19 mRNA\nN=63272512/14-05/06\nChi-Square12/14-05/06\nPRR\nCEREBRAL THROMBOSIS 194 69.78 73.46\nINTERMENSTRUAL BLEEDING 1323 481.57 62.62\nCEREBRAL VENOUS SINUS THROMBOSIS 155 55.02 58.69\nHEAVY MENSTRUAL BLEEDING 4246 1543.71 53.59\nINTENTIONAL PRODUCT USE ISSUE 141 49.72 53.39\nPOSITIVE AIRWAY PRESSURE THERAPY 789 283.64 49.79\nPULMONARY THROMBOSIS 610 218.11 46.20\nDISEASE RECURRENCE 227 79.98 42.98\nHYPERPYREXIA 111 38.38 42.03\nPOSTMENOPAUSAL HAEMORRHAGE 521 184.41 39.46\nPOLYMENORRHOEA 684 241.57 37.00\nRIGHT VENTRICULAR DYSFUNCTION 96 32.71 36.35\nINTENTIONAL DOSE OMISSION 94 31.96 35.59\nABNORMAL UTERINE BLEEDING 82 27.43 31.05\nOLIGOMENORRHOEA 564 196.16 30.51\nCEREBELLAR STROKE 80 26.68 30.29\nSUSPECTED COVID-19 550 190.86 29.75\nCEREBRAL MASS EFFECT 75 24.79 28.40\nRIGHT VENTRICULAR DILATATION 73 24.04 27.64\nDYSMENORRHOEA 1821 631.80 27.58\nTHROMBECTOMY 348 118.98 26.35\nMYOCARDIAL STRAIN 64 20.65 24.23\nHAEMOFILTRATION 62 19.90 23.48\nIMPLANTABLE CARDIAC MONITOR INSERTION 61 19.52 23.10\nTRANSVERSE SINUS THROMBOSIS 60 19.15 22.72\nMATERNAL EXPOSURE DURING BREAST FEEDING 292 97.84 22.11\nBODY HEIGHT DECREASED 57 18.02 21.58\nMENSTRUAL DISORDER 2435 822.34 20.96\nMENSTRUATION IRREGULAR 3240 1094.66 20.79\nMESENTERIC VEIN THROMBOSIS 54 16.90 20.45\nNIH STROKE SCALE ABNORMAL 54 16.90 20.45\nNIH STROKE SCALE 53 16.52 20.07\nCORONARY ARTERY DISSECTION 52 16.15 19.69\nJUGULAR VEIN THROMBOSIS 52 16.15 19.69\nLEFT VENTRICULAR DILATATION 51 15.77 19.31\nANOSMIA 3546 1186.66 19.18\nNEUROLOGIC NEGLECT SYNDROME 50 15.40 18.93\nCEREBRAL ARTERY OCCLUSION 98 31.29 18.55\nVITAL SIGNS MEASUREMENT 146 47.19 18.43\nILLNESS 4279 1423.54 18.21\nINTRACARDIAC THROMBUS 95 30.16 17.99\nLYMPHOPENIA 94 29.79 17.80\nTHROMBOEMBOLECTOMY 47 14.28 17.80\nVACCINATION SITE URTICARIA 322 104.80 17.42\nCOR PULMONALE ACUTE 46 13.90 17.42\nHEPATIC MASS 46 13.90 17.42\nWRONG PATIENT 45 13.53 17.04\nPREMENSTRUAL PAIN 44 13.16 16.66\nPRODUCT RECONSTITUTION QUALITY ISSUE 44 13.16 16.66\nTOTAL LUNG CAPACITY DECREASED 44 13.16 16.66\nPERIPHERAL ARTERY OCCLUSION 43 12.78 16.28\nANTICOAGULANT THERAPY 3684 1204.20 16.22\nCOLON CANCER 41 12.04 15.53\nSYMPTOM RECURRENCE 163 51.45 15.43\nACUTE CARDIAC EVENT 40 11.67 15.15\nPERIPHERAL ARTERY THROMBOSIS 78 23.79 14.77\nCARDIOVASCULAR SYMPTOM 39 11.29 14.77\n\n38 \n CDC and the Food and Drug Administration (FDA) chose to rely on \nEmpirical Bayesian (EB) data mining —a more robust technique \nused to analyze disproportionate reporting —rather than PRR \ncalculations to mitigate potential false signals. . . . Given the strengt h \nof the EB data mining method, CDC and FDA plan to continue \nrelying upon EB data mining moving forward.211 \n \nGiven that it decided to abandon the PRR data and rely upon the EB data, our firm requested the \nEB data mining results from FDA through FOIA and was denied. Hence, we commenced a lawsuit \nagainst the FDA to obtain the EB data results which  remains ongoing.  \n \nVSD  \n \nThe next system the CDC lists as a vaccine safety surveillance tool is the Vaccine Safety Datalink \n(VSD ). While this system could be helpful in assessing vaccine safety, that is not currently the \ncase. Until around 2001, the VSD was maintained at the CDC. Thus, independent scientists were \nable to obtain access to the VSD at the request of members of Congres s and through other legal \nmeans. The studies these independent scientists published identified various harms associated with \nvaccination. CDC then moved the VSD to an industry trade association starting in 2001 which \ntook it out of the reach of the Freedom  of Information Act and also limited the data to only \nscientists and studies it approved.212 This resulted in selection bias with regard to studies that were \nallowed to access and be published using the VSD. Moreover, every study published using the \nVSD violates scientific standards because the underlying data is almost never available for \ninspec tion by the public and other scientists .213 Refusal to make this data available raises serious \nconcerns regarding reproducibility and transparency. HHS regulations provide severe penalties if \nresearchers, using HHS funding, refuse to share data underlying their studies, but the CDC does \nnot apply t his same standard to its own VSD studies.214 \n \nPutting these issues aside, the VSD is not typically used to study long term health conditions. \nWhile the CDC has acknowledged that public stakeholders “have expressed more concerns about \nlong-term than short -term health outcomes” and that “long -term healt h outcomes have been less \nwell-studied in the context of vaccine safety,” VSD is geared toward assessing short -term, and not \nlong-term, health outcomes:  \n \nThe current safety surveillance systems such as the VSD … already \nhave extensive systems in place to assess short -term outcomes … \n[despite the fact] the childhood immunization schedule is essentially \na long -term exposure, occurring over 18 to 24 months, [a nd hence] \n \n211 https://www.documentcloud.org/documents/23940343 -sen-johnson -letter -to-fda-on-eb-data-mining . \n212 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4708093/ .  \n213 https://www.cdc.gov/vaccinesafety/ensuringsafety/monitoring/vsd/accessing -data.html . \n214 https://www.federalregister.gov/documents/2016/09/21/2016 -22379/nih -policy -on-the-dissemination -of-nih-funded -\nclinical -trial-information . \n39 \n long-term adverse events may be more biologically plausible than \nshort -term events .215 \n \nThe deidentified data in the VSD, paid for by taxpayers, should be available to the public so that \nindependent scientists can conduct vaccine safety studies.  Until that data is released and any \nclaimed results using this data replicated, it is an improper tool to reach any conclusion regarding \nvaccine safety.  \nV-safe \n \nCDC’s V -safe vaccine safety system is a smartphone -based program which uses “text messages \nand web surveys to ask how [users] feel, including if [users] experience any side effects after \nvaccination .”216 It was first developed and used with COVID -19 vaccines but has since been \nexpanded for other vaccines. As explained by the CDC, the program “helps CDC gather important \ninformation and monitor any potential side effects in real time so scientists can quick ly study them \nand determine if there is a safety concern with a particular vaccine.”217 The CDC explains that \n“[t]his information helps [it] communicate timely and transparent information about the safety of \nvaccines to public health officials, healthcare providers, and the public.”218 \n \nOn November 19, 2020, the CDC published a protocol for developing V -safe titled “V -safe active \nsurveillance for COVID -19 vaccine safety” ( V-Safe Protocol ).219 The V -Safe Protocol explains \nthat “[t]he purpose of v -safe surveillance is to rapidly characterize the safety profile of COVID -19 \nvaccines when given outside a clinical trial setting and to detect and evaluate clinically important \nadverse events and safet y issues that might impact policy or regulatory decisions.”220  \n \nV-safe was launched simultaneously with the release of the first COVID -19 vaccine in December \n2020. Approximately 10 million individuals signed up for V-safe, around 9 million of whom \nregistered between December 2020 and April 2021.221 \n \nThis period from December 2020 to April 2021 was a period when there were no Covid -19 vaccine \nmandates yet and there was high public interest in receiving this product. The data submitted by \n10 million V -safe users is likely a good reflection of the experi ence of the larger population of 265 \nmillion Americans who received at least one dose of a COVID -19 vaccine.  \n \nV-safe collected data from users in two ways. The first was check -the-box options limited to (a) \nsymptoms and (b) health impacts. The second was using free -text fields.  \n \n215 https://www.cdc.gov/vaccine -safety/media/pdfs/white -paper -safety -508.pdf?CDC_AAref_Val=https://www.cdc.\ngov/vaccinesafety/pdf/WhitePaperSafety_WEB.pdf .   \n216 See https://www.cdc.gov/coronavirus/2019 -ncov/vaccines/safety.html  (listing v -safe as one of the ways “CDC \nexpanded and strengthened the country’s ability to monitory vaccine safety”).  \n217 Id.  \n218 Id. \n219 https://web.archive.org/web/20210102024902/https://www.cdc.gov/vaccinesafety/pdf/V -safe-Protocol -508.pdf .  \n220 Id. at 1.  \n221 https://data.cdc.gov/Public -Health -Surveillance/v -safe-COVID -19/dqgu -gg5d/about_data .  \n40 \n  \nWith regard to check -the-box symptoms, V -safe users were asked to select one or more of 10 listed \nsymptoms that occurred within the first week after vaccination. These symptoms are those that the \nCDC explains are normal after vaccination and are a sign the  vaccine is working by producing an \nimmune response. As the CDC explains: “Any side effects from getting the vaccine are normal \nsigns the body is building protection.”222 Meaning, the check -the-box symptoms data collected by \nV-safe had effectively no value in assessing safety of the COVID -19 vaccines. Indeed, the 10 \nmillion V -safe users reported over 70 million check -the-box symptoms, and this did not raise \nconcerns for th e CDC as seen from the studies the CDC published reflecting these high rates of \ncheck -the-box symptoms.223  \n \nThe only other check -the-box safety information collected (other than the 10 listed symptoms) was \nwhether users reported needing medical care, missed school or work, or could not perform normal \ndaily activities following their vaccination ( “health impact data ”). If a user selected that he or she \nneeded medical care, the user was then also asked to select whether he or she sought telehealth, \nurgent care, emergency care, or was hospitalized.  \n \nThe health impact data was collected during the first week, then weekly for the first six weeks, and \nthen at 3, 6, and 12 months after injection. In contrast, the check -the-box symptoms data was \ncollected for only the first week after injection. Since the CDC dubbed V -safe a “real time” \nsurveillance program, presumably the health impact data is the data the CDC intended to use to \nrapidly detect any safety issues .224  \n \nSince 2021, the CDC published dozens of studies to support its claim that COVID -19 vaccines are \nsafe. Primary data used in these studies is V -safe’s health impact data, with a focus on the rate of \npeople who reported needing medical care after the vaccine.  The studies form a core of the CDC’s \nsupport for the safety of COVID -19 vaccines. However, the studies only report the first week of \nhealth impact data after injection despite the fact injuries from COVID -19 vaccines can occur after \nthe first week .225  \n \nWhen the check -the-box data was released to the public, following over two years of litigation by \na non -profit group to compel release of the data, it reflected that 7.7% of V -safe users reported \nneeding medical care after a COVID -19 vaccine and an additional 25% of V -safe users reported \n \n222 https://www.cdc.gov/coronavirus/2019 -ncov/vaccines/different -vaccines/how -they-work.html . \n223 See e.g. , https://www.cdc.gov/mmwr/volumes/71/wr/mm7107e1.htm ; https://www.cdc.gov /mmwr/ volumes/70/wr/\nmm7039e4.htm ; https://www.cdc.gov/mmwr/ volumes/70/wr/mm7018e2. htm; https://jamanetwork.com/journals/jama/\nfullarticle/2778441 ; https://www.cdc.gov/mmwr/ volumes/ 70/wr/mm7008e3.htm ; https://www.cdc.gov/mmwr/volumes/\n70/wr/mm705152a1.htm ; https://www.cdc.gov/mmwr/volumes/70/wr/mm7031e1.htm .  \n224 https://www.cdc.gov/coronavirus/2019 -ncov/vaccines/safety.html  (“These platforms give CDC scientists information \nabout the safety of COVID -19 vaccines in real time.”).  \n225 For example, myocarditis can arise at least 42 days after vaccination.  See https://pubmed.ncbi.nlm.nih.gov/34614329/  \nat Figure 1. T hrombosis with thrombocytopenia syndrome (TTS), which can also be caused by the COVID -19 vaccine, \ncan arise up to 18 days after vaccination. See https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2021 -12-\n16/02 -COVID -See-508.pdf  at slide 16.  \n41 \n missing school or work or being unable to perform normal activities after receiving a COVID -19 \nvaccine.226  \n \nThat finding was not in accord with what the CDC had been reporting to the public, as it reflected \nthat nearly 1 in 13 individuals in the V -safe system sought medical care after a COVID -19 vaccine, \nand on average, users sought medical care two to three tim es each. Since V -safe was supposed to \nassess safety, and the only metric that appears to have provided any such measure was when users \nreported seeking medical care, it is unclear what measure of vaccinees having to seek medical \nwould have needed to occur in order to raise a safety concern for the CDC.  \n \nFurthermore, the CDC could have designed V -safe to be a rapid and useful safety system by \nincluding check -the-box options for harms that COVID -19 vaccines can or were suspected to cause. \nFor example, a check -the-box option for myocarditis or for chest pain . As reflected in the first \nversion of the V -safe Protocol, prior to the program’s launch, it listed adverse events of special \ninterest ( AESI ) in a chart titled Prespecified Medical Conditions:  \n \n \nThis list included acute myocardial infarction, anaphylaxis, coagulopathy, COVID -19 Disease, \ndeath, Guillain -Barre Syndrome, Kawasaki disease, Multisystem Inflammatory Syndrome in \nChildren, Multisystem Inflammatory Syndrome in adults, myocarditis/pericardi tis, \nnarcolepsy/cataplexy, pregnancy and prespecified conditions, seizures/convulsions, stroke, and \ntransverse myelitis.  \n \nThe CDC also identified all but two (pregnancy and coagulopathy) of these AESIs in an October \n22, 2020 presentation titled “CDC post -authorization/post -licensure safety monitoring of COVID -\n19 vaccines .”227 Many of these AESIs were also identified in a July 2020 NEJM study,228 as well \nas in an October 16, 2020 JAMA article.229  \n \n226 https://icandecide.org/v -safe-data/ .  \n227 See https://cacmap.fda.gov/media/143530/download  at 31. \n228 See https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377258/#ap2 .  \n229 See https://jamanetwork.com/journals/jama/fullarticle/2772137 .  \n\n42 \n  \nNonetheless, the CDC did not include in the V -safe system any check -the-box options for these \nharms or for common symptoms from these harms. Had the agency done so, it would have enabled \nthe CDC and the scientific community to calculate a rate for which V -safe users had myocarditis, \nor other adverse events that had been prespecified by the CDC as potential  problems ( e.g., strokes, \nseizures, etc.). Instead, the CDC limited potential reporting of such adverse events to free -text \nfields to which fewer people w ould report issues and which would be more difficult to standardize.  \n \nV-safe was plainly designed to reach a finding that COVID -19 vaccines are safe rather than \ndesigned to assess whether COVID -19 vaccines are safe. It only included symptoms that the CDC \nconsiders normal and reflect the vaccine is creating immunity, which is  also reflected by the fact \nit only tracked those symptoms for one week after administration. It did not include on the list of \nsymptoms and conditions those that it listed as ones of concern/special interest. It also did not, of \nits own accord, reveal the  health impact data to the public, which appears to be the only actual \nuseful data for assessing safety; only after years of legal demand and litigation did it release the \ndata, which revealed that 7.7% of V -safe users reported seeking medical care after a  COVID -19 \nvaccine, and on average two to three times per user.  \n \n CISA  \n \nCDC regularly claims that the Clinical Immunization Safety Assessment (“ CISA ”) is a critical \npart of the safety monitoring of vaccines. CDC describes CISA as: “ a national collaborating \nnetwork of vaccine safety experts from the CDC’s Immunization Safety Office (ISO), eight \nmedical research centers, and other partners” that was established “to improve the understanding \nof adverse events following immunization at t he individual patient level .”230 CISA, like the other \nsafety surveillance programs, is also problematic for a few reasons.  \n \nFor one, as CDC states, “CISA provides consultations for U.S. healthcare providers with complex \nvaccine safety questions about their patients .”231 Our firm has been advised by many who suffered \nadverse events after their vaccination and who were not believed  by their medical providers . Those \nindividuals  were unable to utilize CISA as it provides consultations only to healthcare providers \nand not to individual patients.  \n \nMoreover, the Principal Investigator of CISA, Dr. Kathryn Edwards,232 has also been a paid \nadvisor to Pfizer233 and/or was compensated by numerous other pharmaceutical companies as a \n \n230 https://www.cdc.gov/vaccinesafety/ensuringsafety/monitoring/cisa/index.html .  \n231 Id.  \n232 https://www.vumc.org/vvrp/person/kathryn -m-edwards -md.  \n233 https://www.cbsnews.com/news/covid -19-vaccine -when -will-be-available -ready/ .  \n43 \n consultant , including Merck,234 GSK,235 Sanofi,236 Bionet,237 Connaught, Smith -Kline Beecham, \nWyeth Lederle, Moderna, Roche .238 \n \nSLIDE 52: RISE IN CHRONIC DISEASE  \nChronic diseases are “conditions that last 1 year or more and require ongoing medical attention or \nlimit activities of daily living or both.”239 Research confirms that the prevalence of chronic \nconditions is on the rise among children. In the early 1980s, data reflects that less than 10% of \nchildren had a chronic disease.240 The current rate is above 40% of children.241  \n \nThe chronic diseases that have risen sharply during the preceding decades are often related to some \nform of immune system dysregulation, including asthma, allergies, ADHD, autism spectrum \ndisorder, atopic dermatitis, diabetes, epilepsy and mental health di sorders.242  \n \nAsthma, allergies, and atopic dermatitis, for example, are caused by a dysregulated immune system \nthat overreacts or reacts to harmless substances.243 ADHD and autism spectrum disorder are highly \nassociated with immune dysregulation.244 Epilepsy can be caused by the immune system attacking \nbrain tissue as well as from neuroinflammation, which can be caused by vaccination.245 Immune \n \n234 https://pubmed.ncbi.nlm.nih.gov/30938299/ . \n235 https://openpaymentsdata.cms.gov/physician/651167 ; https://academic.oup.com/jid/article/222/8/1413/5510417 .     \n236 https://www.nejm.org/doi/10.1056/NEJMoa050824 ; https://openpaymentsdata.cms.gov/physician/651167 . \n237 https://pubmed.ncbi.nlm.nih.gov/32753370/ .   \n238 https://pubmed.ncbi.nlm.nih.gov/32753370/ ; https://pedsinreview.aappublications.org/content/19/ 2/68; https://\npubmed.ncbi.nl m.nih.gov/10617749/ .  \n239 https://www.cdc.g ov/chronic -disease/about/index.html . \n240 https://pubmed.ncbi.nlm.nih.gov/3944229/  (https://perma.cc/NGA9 -93KW ) (“According to data from the National \nHealth Interview Survey (NHIS) [1979 -1981] over two million children under 17 years (3.8%) are afflicted by chronic \nconditions that cause some limitation of activity.”); https://pmc.ncbi.nlm.nih.gov/articles/PMC1646496/  \n(https://perma.cc/KN4A -94TV ) (“Data from the National Health Interview Survey indicate that the prevalence of \nactivity -limiting chronic conditions among children under age 17 years doubled between 1960 and 1981, from 1.8 to \n3.8 per cent.”); https://pubmed.ncbi.nlm.nih.gov/9551003/  (https://perma.cc/JTZ5 -JBNK ) (Among “children younger \nthan 18 years who were included in the 1992 -1994 National Health Interview Survey … [a] significant proportion of \nchildren, estimated at 6.5% of all US children, experienced some degree of disability.”); https://www.cdc.gov/chronic -\ndisease/about/index.html  (https://perma.cc/N4GT -38L2 ) (“Chronic diseases are defined broadly as conditions that last \n1 year or more and require ongoing medical attention or limit activities of daily living or both.”).  \n241 https://pubmed.ncbi.nlm.nih.gov/21570014/ . \n242 https://pmc.ncbi.nlm.nih.gov/articles/PMC5010981/ ; https: //www.academicpedsjnl.net/article/S1876 -\n2859(25)000 35-X/fulltext . \n243 https://pubmed.ncbi.nlm.nih.gov/30741719/ .  \n244 https://pubmed.ncbi.nlm.nih.gov/28849096/ ;https://pubmed.ncbi.nlm.nih.gov/39426507/ ; https://pmc.ncbi.nlm.  \nnih. gov/articles/PMC5373490/ ; https://pubmed.ncbi.nlm.nih.gov/39481220/ .  \n245 https://pmc.ncbi.nlm.nih.gov/articles/PMC10906461/ .  \n44 \n “system dysfunction represents a key mechanism in the onset and pathophysiology of mood \ndisorders.”246 \n \nThis widespread disregulation of children’s immune systems has reached concerning  rates and \nimposes substantial costs upon society. According to the CDC, “[n] inety percent of the nation’s \n$4.5 trillion in annual health care expenditures are for people with chronic and mental health \nconditions.”247 The country’s cost of chronic disease is “projected to accumulate by 2030 to more \nthan $42 trillion, with medical outlays and productivity losses costing $8,600 per person.”248 \n \nThe sharp rise in immune dysregulation -mediated chronic diseases over the preceding decades \nindicates that one or more environmental factors have caused the widespread dysregulation of our \nchildren’s immune systems. In considering what could be causing wid espread immune system \ndysregulation, it is critical to rule out products administered specifically to permanently modify \nthe immune system of our children: vaccines. This is especially true given that the rise in these \nimmune and immune -mediated disorders has occurred in lock step with the expansion and level of \nuptake of CDC -recommended vaccines.  \n \nLeading up to and until the late 1980s, the CDC’s immunization schedule had three routine \nvaccines: DTP (diphtheria tetanus pertussis), MMR (measles mumps rubella) and OPV (oral polio \nvaccine).249 The first two were injected and the latter was given by oral drop.  \n \nIn the 1980s, the uptake of these three products was also far below current uptake levels. According \nto the CDC, as of 1985, the National Health Interview Survey found that among children, only \n63.6% had 3 or more doses of DTP, 61.2% had received 1 or more  doses of MMR, and 53.6% had \nreceived 3 or more doses of OPV.250 Uptake in children today is above 90% for all three of these \nvaccines or their current equivalent.251  \n \nMoreover, the administration of  these three vaccines have increased from 7 injections in 1985 (1 \nMMR, 5 DTP, and 1 Td) to 13 injections for the equivalent vaccines in 2025 (2 MMR, 5 DTaP, 2 \nTdap, including one during pregnancy, and 4 IPV).252 In addition, over 10 additional routine \nvaccines have been added to the CDC’s neonatal and childhood vaccine schedule since 1986, each \nwith multiple doses, including Hep B (3 doses), Hib (3 or 4 doses), and VAR (2 doses) in the \n1990s, and PCV (4 doses), IIV (between 1 and 2 d oses annually), Hep A (2 doses), MenACWY, \nRV (2 or 3 doses), HPV (2 or 3 doses), and RSV (1 dose during pregnancy) since 2000.253  \n \n246 https://pubmed.ncbi.nlm.nih.gov/39681901/ .  \n247 https://www.cdc.gov/chronic -disease/data -research/facts -stats/?CDC_AAref_Val=https://www. cdc.gov/chronic\ndisease/about/costs/index.htm .  \n248 https://doi.org/10.1146/annurev -publhealth -040218 -044008 .  \n249 https://www.cdc.gov/vaccines/schedules/images/schedule1983s.jpg . \n250 https://web.archive.org/web/20190618125412/https:/www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendic\nes/e/coverage -levels.pdf . \n251 https://www.cdc.gov/childvaxview/about/interactive -reports.html .  \n252 Compare https://www.cdc.gov/vaccines/schedules/images/schedule1983s.jpg , with https://www.cdc.gov/\nvaccines/ hcp/imz -schedules/child -adolescent -age.html .  \n253 https://www.cdc.gov/vaccines/hcp/imz -schedules/resources.html# .  \n45 \n  \nThe increase in the number of vaccines since 1986 is especially pronounced during pregnancy and \nthe first year of a baby’s life. By a child’s first birthdate, assuming no combination vaccines are \nused, a child in 1986 following the CDC’s vaccine schedule would have received 3 injections with \na total of 7 injections throughout childhood, whereas a child in 2025 will receive 25injections by \nthe child’s first birthdate with a total of over 50 injections  throughout childhood.254  \n \nWhen studying environmental factors which could be causing the immune system of our children \nto dysregulate en masse , one factor that must be ruled out is vaccines and whether the increase in \nvaccine uptake and number of vaccines, especially during infancy, have been a contributing factor. \nWhile c orrelation does not equal causation, it does provide a safety signal that merits investigation, \nincluding because vaccines are intended to and do systemically modify the immune system and, \nthus, could be the cause of widespread immune system dysregulation.  \n \nSee the Appendix which r eview s select  chronic diseases that have risen sharply in the last few \ndecades and discuss studies related to vaccines and these diseases.  \n \n \nSLIDE 5 3: ALUMINUM ADJUVANTS  \nAfter injection, a luminum adjuvant s in vaccine s are picked up by a variety of immune -reactive \ncells and is then carried all around the body including into the brain.  There are animal studies that \ndemonstrate this and the re are clinical studies of autism brain tissue that support th ose animal \nstudies.255  \n \n \nSLIDE 56: TRANSMISSION  \n \nWhile s ome live -attenuated vaccines, such as Varivax for varicella, generally prevent transmission \nof the target pathogen in most recipients for an extended duration post -vaccination , many of the \nvaccines routinely recommended by CDC,  including the current pertussis, tetanus,  and polio \nvaccines, do not prevent transmission or infection of the diseases they target . See among other \nsources: https://www.cdc.gov/poliovirus -containment/diseaseandvirus/  (“Inactivated poliovirus \nvaccine (IPV)  [the exclusive polio  vaccine used in the United States ] … does not stop transmission \nof the virus. ”); https://www.cdc.gov/mmwr/volumes/71/wr/mm7133e2.htm  (“IPV does not \nprevent intestinal infection and therefore does not prevent poliovirus transmission. ”); \nhttps://www.fda.gov/media/181937/download  (“aP [acellular  pertussis] containing vaccines  [the \nexclusive pertussis vaccine used in the United States ] induce helper T cells (TH2) memory and \nneutralizing antibody responses that effectively prevent symptomatic disease but fail to prevent \ncolonization and carriage. ”) https://pubmed.ncbi.nlm.nih.gov/31333640/  (“Natural infection \nevokes both mucosal and systemic immune responses, while aPVs [acellular pertussis vaccine ] \ninduce only a systemic immune response. …  Mucosal immunity is essential to prevent \n \n254 Id.  \n255 Khan 2013 https://pubmed.ncbi.nlm.nih.gov/23557144/ ; Crépeaux 2015 https://pubmed.ncbi.nlm.nih.\ngov/26384437/ ; Eidi 2015 https://pubmed.ncbi.nlm.nih.gov/26082187/ ; Gherardi 2015 https://\npubmed.ncbi.nlm.nih.gov/25699008/ ; Masson 2022 https://pubmed.ncbi.nlm.nih.gov/36112128/ ; Angrand 2022 \nhttps://pubmed.ncbi.nlm.nih.gov/36136483/ ; Mold 2020 https://pubmed.ncbi.nlm.nih.gov/32368656/ .  \n46 \n colonization and transmission of B. pertussis  organisms. Consequently, preventive measures such \nas aPVs that do not induce a valid mucosal response can prevent disease but cannot avoid infection \nand transmission.  … aPV pertussis vaccines do not prevent colonization. Consequently, they do \nnot reduce the circulation of B. pertussis and do not exert any herd immunity effect.”); \nhttps://www.cdc.gov/vaccines/basics/explaining -how-vaccines -work.html  (Tetanus is “not \ncontagious ” from person to person.”); https://web.archive.org/web/20250112105810/\nwww.cdc.gov/vaccines/vpd/mening/hcp/about -vaccine.html  (“data suggest MenACWY vaccines \nhave provided protection to those vaccinated, but not to the larger, unvaccinated community \nthrough population or herd immunity ”). \n \n \nSLIDES: 66 -73: MORTALITY  \n \nThe CDC estimate that vaccines saved 1.1 million lives in the United States between 1994 and \n2023 is routinely cited by third parties even though it is, at best, unreliable.  \n \nFirst, the article including this estimate is not published in a journal, but rather in the MMWR. \nCDC’s own guidelines for the MMWR permit the publi cation of only articles that align with CDC \npolicy which results in selection bias. As explained by the CDC’s policies for publishing an \nMMWR report: “By the time a report appears in MMWR, it reflects, or is consistent with, CDC \npolicy .”256 And the CDC’s policy is that vaccines are safe and effective.  \n \nSecond, this report provides  no confidence intervals for its estimates. This is because they are \nguesswork. The true rate could be that the vaccine s used in the United States from 1994 to 2023 \ncould have saved 1.1 million lives or they could have result ed in 2 million deaths. Since the report \nprovides no bounds for its claims, either claim could be true.  \n \nThird, the study explains that “factors other than immunization (e.g., hygiene…) might have \ncontributed to lower disease risks in recent decades, and reductions resulting from these \ncontributions have not been incorporated into the model .” (Emphasis  added.) Meaning, it did not \naccount for any other advancement or factor that may have improved health outcomes. This alone \nrenders this CDC promotion “study” wholly unreliable . It is also why it has no bounds for its \nestimates because it cannot calculate them with any confidence.  \n \nFinally, just a simple review of the data shows its estimate is contrary to the data . While it claims \nvaccines saved 1.1 million lives between 1994 and 2023, it takes only looking at the actual real -\nworld data to see that this figure is without any merit . This can be seen by reviewing three diseases \nthe report claims account for almost the entire 1.1  million lives purportedly saved: diphtheria, \nhepatitis B, and measles.  \n \n Diphtheria. Around 750,000 of the 1.1  million lives (over 68%) that CDC claims were \nprevented are from diphtheria. That means that it claims 25,000 lives were saved per year by this \nvaccine. That figure has no basis in reality . \n \n \n256 https://www.cdc.gov/mmwr/author_guide_rrss.html .  \n47 \n The first vaccine for diphtheria was introduced in 1926. \nBetween 1900 and 1926, as the population rose, the death \nrate from this disease had already declined 81%, from \n40.3 to 7.8 deaths per 100,000 individuals .257 A vaccine \nhad nothing to do with this sharp decline since no vaccine \nof any kind for diphtheria existed until 1926. The further \ndecline from 1926 until at least the mid -1940s also had \nlittle or nothing to do with the vaccine because it was \nrarely, if ever , used outside of certain demographics in \nmajor cities, and diphtheria mortality declined at a \nsimilar rate in areas with or without its use.258 To the \nright is an official government chart reflecting same.259 \nSo, even as the population increased, the data clearly \nshows an 81% mortality decline from 1900 to 1926, a \n97.3% decline from 1900 to 1940, and a 97.8% decline \nfrom 1900 to 1948; hence, using any of these time \nperiods , it is plain vaccination had little to do with almost \nall of the decline in mortality from diphtheria in the last \ncentury :260  \n \nIn 1949, DTP was first licensed, and coverage of this vaccine began to improve, and in 1948, there \nwas a total of 634 deaths from diphtheria.261 Yet, this MMRW report claims diphtheria vaccine is \nnow saving 25,000 lives a year in the United States. (Also note that in 1985, the coverage for only \nthree doses, let alone the six recommended today, was still only 63.6%.262) \n \n \n257 https://www.cdc.gov/nchs/data/vsus/vsrates1940_60.pdf . \n258 https://pmc.ncbi.nlm.nih.gov/articles/PMC1997101/pdf/pubhealthreporig01174 -0001.pdf  (“The simultaneous \ndecline in diphtheria morbidity and mortality rates in all age groups of individual States located in different sections \nof the country, which began after a cyclic increase in incidence between 1915 and 1925, suggests the operation or \ninfluence of other factors besides, or in addition to, artificially induced immunity. Studies such as that included in the \n1930 White House Conference on Child Health and Protection indicated that immunization programs were reaching \na relatively large propo rtion of children in some areas or cities and a very low proportion in others , as late as 1930. In \nspite of this wide variation, both morbidity and mortality began to decline rapidly after 1925 in all States \nsimultaneously.”); https://www.cdc.gov/pinkbook/hcp/table -of-contents/chapter -7-diphtheria.html  (“[D]iphtheria \ntoxoid -containing vaccines became available in the 1940s” and “universal childhood vaccination program which \nincluded diphtheria toxoid -containing vaccines beginning in the late 1940s.”).  \n259 https://www.cdc.gov/nchs/data/vsus/vsrates1940_60.pdf  at 84 . \n260 The death rate per 100,000 individuals in the United States in 1900, 1940, and 1948 for diphtheria was 40.3, 1.1, \nand 0.4, respectively, for tetanus was 2.4, 0.4., and 0.3, respectively, and for pertussis was 12.2, 2.2, and 0.8, \nrespectively. https://www.cdc.gov/nchs/data/vsus/vsrates1940_60.pdf . \n261 https://www.cdc.gov/Mmwr/preview/mmwrhtml/00038200.htm . \n262 https://web.archive.org/web/20190618125412https:/www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendi\nces/e/coverage -levels.pdf . \n\n48 \n This claim becomes more nonsensical when considering that even after six childhood doses,263 \nadults require a booster dose every ten years in adulthood,264 and about 40% of adults skip these \nboosters.265 Despite a large portion of adults not receiving boosters, the last case of respiratory \ndiphtheria in the United States was nearly three decades ago.266 This may reflect the literature \nwhich supports that its harmful effects may be counteracted by improvement in certain living \nconditions .267  \n \nThere are diseases that had a high mortality in the United States that disappeared without a vaccine. \nFor many of these diseases, researchers sought to develop a vaccine but failed. For example, scarlet \nfever was one of the deadliest infectious diseases fo r children in 1900, with a death rate of 9.6 \ndeaths per 100,000 children. Researchers sought to develop a vaccine but repeatedly failed. By the \n1950s, deaths from scarlet fever had significantly declined and by the late 1900s, deaths from \nscarlet fever wer e essentially non -existent.268  \n \nHad a vaccine for scarlet fever been developed in the 1920s, 40s, or 60s, that vaccine may still be \non the childhood schedule today, and its use considered essential for controlling scarlet fever , and \nthe MMWR article may estimate that this vaccine today also saves thousands of lives a year from \nscarlet fever.  \n \nScarlet fever and diphtheria are similar in that each is caused by a bacterium that releases a \npotentially harmful toxin when the bacterium has been “infected” by a certain virus. Both diseases \ncause sore throats, and many doctors, without a lab test, will confuse diphtheria with scarlet fever, \nand vice versa. These two diseases also both declined at nearly the same rate beginning in 1900.  \n \nIn any event, the CDC’s claim that 750,000 lives have been saved from diphtheria between 1994 \nand 2023 is without footing given the failure to account for the actual mortality data, other factors \nthat reduced morality from diphtheria, the lack of any bounds to its claim, the lack of population \nwide immunity and other factors , and the objective  data regarding this disease . The reality is likely \nfar closer to what occurred with scarlet fever absent vaccination.   \n \n Hepatitis B. As another example, the CDC article claims Hep B vaccines saved over 90,000 \nlives from 1994 to 2023, amounting to over 3,000 lives purportedly saved per year. This claim \nagain defies the data because i n 1980,  the year before the first Hep B vaccine was introduced,  there \nwere 294 deaths in the United States from Hep B.269  \n \n \n263 https://www.cdc.gov/vaccines/hcp/imz -schedules/downloads/child/0 -18yrs -child -combined -schedule.pdf . \n264 https://www.cdc.gov/vaccines/hcp/imz -schedules/adult -age.html . \n265 https://www.cdc.gov/adultvaxview/publications -resources/vaccination -coverage -adults -2019 -2020.html .  \n266 https://www.cdc.gov/diphtheria/php/surveillance/index.html . \n267 https://pubmed.ncbi.nlm.nih.gov/2151460/ ; https://pubmed.ncbi.nlm.nih.gov/7830565/ ; https://pubmed.ncbi.nlm.\nnih.gov/4326212/ ; https://pubmed.ncbi.nlm.nih.gov/189004/ .  \n268 https://www.statnews.com/2017/11/27/scarlet -fever -cases/ .  \n269 https://web.archive.org/web/20190615081539/https:/www.cdc.gov/vaccines/pubs/pinkbook/downloads/ appen\ndices/e/reported -cases.pdf . \n49 \n  Measles . As a final example, CDC’s advertising article claims measles vaccine saved \n85,000 lives from 1994 to 2023, amounting to over 2,700 lives purportedly saved per year. This \nclaim again defies the data. The first measles vaccine came on the market in 1963.270 In the years \nleading up to the first measles vaccine in 1963, the CDC data reflects around 400 deaths from \nmeasles each year.271 There were also around 4.2 million births each year in the late 1950s and \nearly 1960s, whereas there was around 3.8 million births each year between 1994 and 2023.272 Yet, \nsomehow, despite improvements in standards of living, medical care, etc., and despite smaller \ncohort of infants and children to infect, this model makes the data defying claim mortality went \nfrom around 400 deaths per year from measles pre -vaccine to  over 2,7000 deaths per year.  \n \nMoreover, the  following U.S. government chart shows the \ndecline in the measles death rate by over 98% from 1900 to \n1960, three years before  the first measles vaccine was \nintroduced in the United States in 1963.273 Meaning, the \nmeasles vaccine had nothing to do with the over 98% \nreduction in the death rate from measles in the United States \nfrom 1900 to 1960.274   \n \nTaking a closer look, the CDC data reflects that in 1900, the \nrate of mortality from measles was 13.3 deaths per 100,000 \nindividuals.275 By 1960, it was 0.2 deaths per 100,000 \nindividuals.276 The same was true for 1961 and 1962.277 \nAnd as noted above, a similar decline of over 99% in \nmeasles deaths occurred between 1900 and 1967 in England \nand Wales, and it was only after that decline that the first measles vaccine was introduced there in \n1968 —five years after its introduction in the United States.278 \nHence, the same factors that caused measles mortality to decline by over 98% from 1900 to 1962 \nwould, absent the vaccine interrupting the ecology of measles, would likely have continued to \ncause a further reduction in the measles mortality rate after 1962.  Meaning, at least a portion of \nthe decline in the 400 deaths per year after  the vaccine was available is no doubt attributable to the \nsame factors that caused a steady decline in the measles death rate for decades prior  to the \n \n270 https://www.cdc.gov/measles/about/history.html .  \n271 https://web.archive.org/web/20190615081539/https:/www.cdc.gov/vaccines/pubs/pinkbook/downloads/appen\ndices/e/reported -cases.pdf . \n272 https://www.cdc.gov/nchs/nvss/births.htm . \n273 https://www.cdc.gov/nchs/data/vsus/vsrates1940_60.pdf  at 85.  \n274 Id. \n275 Id. \n276 https://www.cdc.gov/nchs/data/vsus/VSUS_1962_2A.pdf .  \n277 Id. \n278 https://webarchive.nationalarchives.gov.uk/ukgwa/20160111174808/http://www.ons.gov.uk/ons/publications/re -\nreference -tables.html?edition=tcm%3A77 -215593 . \n\n50 \n introduction of the measles vaccine. Therefore, even without the measles vaccine, the death rate \nwould have, no doubt, continued to decline after 1963.  \n \nIn pockets of the country with poor nutrition, sanitation, and water, deaths from any pathogen, \nincluding measles, can occur at a higher rate. Those conditions still existed in some pockets of the \nUnited States in the early 1960s. As living conditions in t hose pockets of America improved with \nthe introduction of clean water, improved sanitation, and better living conditions, deaths from \nmeasles declined, which is what typically occurs when these conditions improve. Also  health care, \nespecially the managemen t and treatment of acute infections, has vastly improved since the 1960s.  \n \nYet, CDC claims that measles vaccines saved  a data defying over 2,800 lives a year from measles \nin the United States between 1994 and 2023. CDC’s study also doesn’t account for the increase in \ndeaths from heart disease and cancer due to the elimination of measles, discussed below  and \nreflected by studies that did not engage in estimates.  \n \nIn sum, the CDC article must conform to CDC policy to be published, does not account for any \nexternal factors, does not account for actual mortality data related to these diseases, and lacks any \nconfidence intervals because its claims have no statistical  reliability. Thus, this study claiming 1.1 \nmillion lives were saved is  unreliable at best.  \n \n \nSLIDE 72: MEASLES  \n \nA study which followed over 100,000 individuals in Japan for approximately 21 years found that \nthose who had been infected with measles and mumps had a statistically significant lower risk of \ndeath from cardiovascular disease, strokes, and heart attacks.279 For example, men who had \nmeasles and mumps (as compared to those who did not have measles and mumps), had a 17% \nreduction in strokes, 20% reduction in cardiovascular disease, and 29% reduction in heart \nattacks.280 Critically, after 21 years, approximately 7% of the men who had measles and mumps \nhad died of cardiovascular disease while approximately 14% of the men who never had measles \nor mumps died of cardiovascular disease.281 Meaning, the men who never had measles and mumps \nwere far more likely to die. The statistically significant findings in this study remained statistically \nsignificant even after adjusting its results for: a ge; body mass; family history of cardiovascular \ndisease; alcohol intake; energy intake; smoking; walking; sports; mental stress; education; and \nhistory of hypertension, cardiovascular disease, or diabetes.282 \nCardiovascular disease is the number one killer of Americans, taking the lives of over 900,000 \nAmericans a year.283 In contrast, as discussed above, according to the CDC, around 400 Americans \ndied of measles annually in the several years before the first measles vaccine arrived in 1963 (and \n \n279 https://pubmed.ncbi.nlm.nih.gov/26122188/  (https://perma.cc/6TJD -5FNZ ). \n280 Id.  \n281 Id. \n282 Id. \n283 https://www.cdc.gov/heart -disease/data -research/facts -stats/ .  \n51 \n this number was declining without a vaccine), and around 40 Americans died annually of mumps \nin the several years before the first mumps vaccine was introduced in 1967.284 \nThis Japanese study  may reflect why measles, unlike most pathogens, may not have died out over \ntime through natural selection . \nSimilar to the finding regarding heart disease, some studies, although not nearly as robust, have \nfound that eliminating measles appears to have caused a measurable increase in certain cancer \nrates. For example, the International Agency for Research on Can cer found that those who never \nhad measles had a 66% increased rate of non -Hodgkin lymphoma and a 233% increased rate of \nHodgkin lymphoma.285 These two cancers are expected to kill an estimated 20,540 Americans in \n2025.286 There are also studies documenting children with Hodgkin’s disease experiencing \nremission when having measles.287 \nLikewise, researchers at the Department of Health Care and Epidemiology at the University of \nBritish Columbia and the Department of Biology at the University of Victoria found that those \nwho never had measles had a 50% increased rate of ovarian cancer, whi ch is expected to kill an \nestimated 12,730 Americans in 2025.288  \nOther studies have reached similar conclusions that measles, as well as mumps, rubella, pertussis, \nand chickenpox, reduce the rate of various forms of cancers, including a study from researchers at \nthe University of Berne, Switzerland that specifically rev iewed these fever -inducing ( i.e., febrile) \ninfections and found that the “study consistently revealed a lower cancer risk for patients with a \nhistory of FICD [febrile infectious childhood diseases].”289 And as an article in The Quarterly \nReview of Biology  explained : \n[D]etailed retrospective and prospective clinical studies … \nsupported the conclusion that frequency of the infectious fever \nepisodes and cancer diagnoses are inversely related (Abel et al. \n1986; Mastrangelo et al. 1998; Kleef et al. 2001; Kleef and Hager \n2006). For example, Grossarth -Maticek et al. (1987) performed a \n10-year prospective cohort study of 1353 patients, concluding that \nepisodes of high fever as a typical reaction to an acute illness during \nthe entire life span are inversely related to later ca ncer incidence. \nKölmel et al. (1992), based on 271 controls versus 139 melanoma \npatients, demonstrated an inverse relation between the number of \n \n284 https://icandecide.org/wp -content/uploads/2023/10/cdc -reported -cases -and-deaths -m-vaccine -preventable -disease\ns-3.pdf . \n285 https://pubmed.ncbi.nlm.nih.gov/16406019/  (https://perma.cc/RHD3 -986B ). See Table 2 and in the Non -\nHodgkin’s Lymphoma (NHL) column divide the odds ratio 1 (never had measles) with .6 (had measles) which results \nin a 66% increased risk, and in the Hodgkin’s Lymphoma (HL) column divide the odds ratio 1 (never had measles) \nwith .3 ( had measles) which results in a 233% increased risk.  \n286 https://seer.cancer.gov/statfacts/html/hodg.html ; https://seer.cancer.gov/statfacts/html/nhl.html .  \n287 https://pubmed.ncbi.nlm.nih.gov/4574047/ . \n288 https://pubmed.ncbi.nlm.nih.gov/16490323/ ; https://seer.cancer.gov/statfacts/html/ovary.html . \n289 https://pubmed.ncbi.nlm.nih.gov/9824838/ . \n52 \n febrile infections and the incidence of malignant melanoma. \nSimilarly, Wrotek et al. (2009) have reported a lower frequency of \nfever in a population of 355 breast tumor patients, compared to 244 \nhealthy women volunteers.290 \nThis article also explained how a survey of studies of spontaneous cancer remissions found that \n“approximately 70% of documented cases [of remission] were immediately preceded by an acute \ninfection associated with high fever” and that this phenomenon has “ been reported for \ncenturies.”291 \nThere are also studies that have found that children who have had measles have far fewer allergies \nand atopic diseases, such as asthma, and adults who have had measles have a reduced risk of \nParkinson’s disease.292 \n \n \nSLIDE 73: MORTALITY TABLE  \n \n \n \n \n290 https://www.journals.uchicago.edu/doi/10.1086/699409 . \n291 Id.  \n292 https://pubmed.ncbi.nlm.nih.gov/19255001/ ; https://pubmed.ncbi.nlm.nih.gov/16854347/ ; https://pubmed.ncbi\n.nlm.nih.gov/4061437/ . \n\n53 \n Diphtheria, Tetanus, & Pertussis  \nScanning down from the top of the table  above , note that when a vaccine was introduced for each \ndisease, U.S. deaths were already rare. Also, m ost of the deaths are attributed to diseases for which \nvaccines were introduced before 1950 (diphtheria, pertussis, and tetanus). The m ortality rate for \nthese three diseases had already precipitously declined before introduction or material use of a \nvaccine and would likely have continued to decline without a vaccine. This chart, using CDC data, \nreflects the decline b etween 1900 and 1949, the year DTP was licensed (as well  as the decline \nbetween 1900 and 1940):293 \n \n \nDiphtheria  was discussed  above in the “Slides: 66 -73: Mortality” section. As for tetanus and \npertussis , the mortality  from these diseases  declined by more than 80 -90% between 1900 and the \n1940s —long before vaccination played a role.294 These vaccines were first introduced into routine \nuse in the late 1940s with the licensure of DTP in 1949. As explained by the NIH: “The whole -\ncell pertussis vaccine became widely available in the United States in the 1940s, although it was \nfirst licensed in 1914. It was crudely made and had limited use until the 1940s, because of reports \nof serious side effects including death.”295 Similarly, as CDC explains regarding the tetanus \nvaccine: “In the late 1940s, tetanus toxoid -containing vaccines  were introduced into routine \nchildhood vaccination .”296  \n \nWhat caused the decline in diphtheria, tetanus, pertussis, and other diseases before introduction of \nvaccination (and thereafter)? This decline is likely caused by many factors, including \nimprovements in sanitation, clean water, nutrition, and medical care . For example, medical care \nacutely improved from the 1940s when the Nobel Prize was awarded for the development of the \nprefrontal lobotomy.297 Even absent a vaccine, the death rate would have continued to decline as \n \n293 The death rate per 100,000 individuals in the United States in 1900, 1940, and 1948 for diphtheria was 40.3, 1.1, \nand 0.4, respectively, for tetanus was 2.4, 0.4., and 0.3, respectively, and for pertussis was 12.2, 2.2, and 0.8, \nrespectively. https://www.cdc.gov/nchs/data/vsus/vsrates1940_60.pdf .  \n294 The death rate per 100,000 individuals in the United States in 1900, 1940, and 1948 for tetanus was 2.4, 0.4., and \n0.3, respectively, and for pertussis was 12.2, 2.2, and 0.8, respectively. \nhttps://www.cdc.gov/nchs/data/vsus/vsrates1940_60.pdf . \n295 https://web.archive.org/web/20250407045130/https://history.nih.gov/display/history/Pertussis . \n296 https://www.cdc.gov/pinkbook/hcp/table -of-contents/chapter -21-tetanus.html .  \n297 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4291941/ . \n\n54 \n living conditions improved, including improvements in medical care, and particularly acute \nmedical care (as well as the decline of certain harmful  medical practices).  \nNonetheless, even assuming the number of deaths from a given disease remained stagnant since \nthe year before the first vaccine for each disease was introduced, the total deaths per year, \ncombined, would be in the low thousands. Every death is a tragedy, bu t this is far from the millions \noften claimed, and the death figures in the above chart  (from a few pages back) do not account for \nthe fact that, even absent a vaccine, the deaths caused by these diseases were almost universally \non a sharp decline.  \nThis decline would have no doubt continued absent vaccination. Meaning, had the vaccines of the \n1940s instead been introduced in the 1960s or 1970s, deaths would have already declined to a mere \nfraction of their 1940s levels.  \nPolio  \n \nNext on the above chart  is polio, the only disease for which a vaccine was introduced in the 1950s. \nIn contrast to every other disease listed, where mortality was sharply declining in the decades \nbefore and after 1900, polio caused almost no deaths in 1900. Instead, it paradoxic ally went from \nbeing nearly innocuous up until around 1890, to then having an increasing rate of mortality, to \nthen having a sharply increasing reported rate of mortality in the few years leading up to 1952. \nFrom that peak, its mortality rate declined shar ply before introduction of the first polio vaccine in \n1955. What this and the greater history about polio reflect is that one or more factors made the \npolio virus more lethal in the first half of the 1900s. As these outside factors declined, so did the \nmortality of polio.  \n \nMeasles, Mumps, & Rubella  \n \nNext on the above chart  is measles, which is also discussed above. The  rate of mortality from \nmeasles declined by over 98% between 1900 and 1962, prior to the introduction of the first measles \nvaccine in 1963 and would have no doubt continued to decline without a measles vaccine.  \n \nNext on the list are mumps and rubella. The first vaccine for each was introduced in 1967 and \n1969, respectively. By the time a vaccine was developed, both diseases caused few deaths annually \nin the several years before a vaccine was developed.298 In addition, between 1960 and 1975, the \nrate of decline in mumps deaths continued at roughly the same pace before and after licensure of \nmumps vaccine in 1967, and the rubella deaths actually increased  after licensure of the first rubella \nvaccine in 1969.299 But either way the number of deaths were few.  \nFurther evidencing that mumps would have disappeared without a mumps vaccine, at most 50% \nto 60% of children received this product in the 1970s, and they only received one dose (and we \n \n298 https://web.archive.org/web/20190615081539/https:/www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendic\nes/e/reported -cases.pdf .  \n299 Id.   \n55 \n now know that even two doses of the same formulation, let alone one, often fails to confer \nprotective immunity), but mortality from mumps reached essentially zero in the 1970s.300  \nHepatitis B  \nNext on the above chart  is Hep B, a primarily blood -borne infection that is typically spread through \nsexual contact and contaminated needles. The first Hep B vaccine was introduced in 1981 and \nmade with human blood plasma from donors who were chronically infected with the Hep B virus. \nIn 1986, a new Hep B vaccine using recombinant DNA technology without human blood was \nlicensed. The mortality from Hep B climbed after introduction of the 1981 vaccine, continued to \nclimb after the introduction of the 1986 vaccine, and ha s never returned to pre -vaccination levels. \nIn 1980, there were 294 deaths in the United States from Hep B.301 Today, there are around 1,700 \ndeaths per year.302 \nHib \nNext on the above chart  is Hib vaccine. The first Hib vaccine was introduced in 1985 but was \nwithdrawn three years later because it was entirely ineffective among children 18 months and \nyounger and may have increased the incidence of disease in older children.303 \nIn 1991, after another Hib vaccine considered effective was introduced, the CDC for the first time \nrecommended a three -dose series of Hib vaccine in the first year of life .304 In 1992, only 28.2% of \nchildren were vaccinated for Hib, and there were a total of 17 deaths from Hib in the United States \nin 1991.305 Yet, the steady decline in mortality from Hib in the prior decades, which had dropped \nrapidly without the existence of any Hib vaccine, is attributed to the Hib vaccine.306 \n \n300 Compare  https://web.archive.org/web/20190615081539/https:/www.cdc.gov/vaccines/pubs/pinkbook/downloads\n/appendices/ e/reported -cases.pdf  with https://web.archive.org/web/20190618125412/https:/www.cdc.gov/\nvaccines/pubs/pinkbook/downloads/appendices/e/coverage -levels.pdf ; see also  https://storage.courtlistener\n.com/recap/gov.uscourts.paed.381331.12.0.pdf ; https://pubmed.ncbi.nlm.nih.gov/35728505/ ; https://pubmed\n.ncbi.nlm.nih.gov/8277201/ . \n301 https://web.archive.org/web/20190615081539/https:/www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendic\nes/e/reported -cases.pdf .  \n302 https://www.cdc.gov/hepatitis/statistics/2021surveillance/hepatitis -b/table -2.8.htm .  \n303 https://web.archive.org/web/20120506033120/http://www.cdc.gov:80/vaccines/pubs/pinkbook/hib.html  (“A pure \npolysaccharide vaccine (HbPV) was licensed in the United States in 1985. The vaccine was not effective in children \nyounger than 18 months of age. Estimates of efficacy in older children varied widely, from 88% to -69% (a negative \nefficacy implies greater disease risk for vaccinees than nonvaccinees). HbPV was used until 1988 but is no longer \navailable in the U nited States.”).  \n304 https://www.cdc.gov/acip -recs/hcp/vaccine -specific/hib.html . \n305 Compare  https://web.archive.org/web/20190615081539/https:/www.cdc.gov/vaccines/pubs/pinkbook/downloads\n/appendices/e/ reported -cases.pdf ; https://www.cdc.gov/acip -recs/hcp/vaccine -specific/hib.html ; with https://web.\narchive.org/web/20190618125412 ; /https:/www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendices/e/coverage -\nlevels.pdf .  \n306 https://www.cdc.gov/nchs/data/statab/hist001r.pdf . \n56 \n Notably, mortality among infants under 1 year of age in the 1980s declined rapidly and sharply \nwhen there was no Hib vaccine for infants (not even an ineffective one like the one introduced in \n1985 for children 18 months and older and then withdrawn a few years later for lack of efficacy).307  \n \nHepatitis A  \n \nNext is Hep A vaccine. In the decade prior to introduction of this vaccine in 1995, there were fewer \nthan 100 deaths every year in the United States from Hep A, with an average of 80 deaths per \nyear.308 Fast forward to the present, there have consistently been more than  100 deaths per year \nfrom Hep A, with an average of 166 deaths during the last five years for which death figures are \navailable.309  \n \nVaricella, Pneumococcal, Meningococcal, & Rotavirus  \n \nFor the final four diseases on the above chart , varicella, pneumococcal, meningococcal, and \nrotavirus, the annual deaths among children for each are so low that the CDC has to estimate them. \nThis was not always the case. Long before vaccines were introduced, each of these diseases did \ncause deaths each year that could be counted. But by the time a vaccine was introduced, the deaths \nhad already become so exceedingly rare, if they occurred at all, that all they could do for these four \ndiseases was estimate . For example, the CDC admits regarding meningococcal: “Much of the \ndecline occurred before the routine use of MenACWY vaccines. In addition, serogroup B \nmeningococcal disease declined even though MenB vaccines were not available until the end of \n2014 .”310 \n \nEven assuming the estimated  deaths are accurate, these estimates reflect that an American, prior \nto a vaccine even existing, had around the same odds of dying from each of these four diseases as \nbeing killed by lightning.  \n \n \n \nAPPENDIX  \n \nWhile the post -licensure vaccine safety literature is limited, this section lists findings from a \nrelatively small pool of existing studies and reviews that either reached a positive finding of a \nconnection between one or more vaccines and a limited number  of diseases or found that the \nexisting evidence is insufficient to reach any definitive conclusion. Either of these findings warrant \nfurther investigation as they evidence that either the studies indicate there is a basis for vaccines \nas a cause or the st udies have not been done to rule out vaccines as a cause of a claimed harm from \n \n307 Id.  \n308 https://web.archive.org/web/20190615081539/https:/www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendi\nces/e/reported -cases.pdf .  \n309 https://www.cdc.gov/hepatitis -surveillance -2022/hepatitis -a/table -1-4.html . \n310 https://www.cdc.gov/vaccines/vpd/mening/hcp/about -vaccine.html .  \n57 \n these products. Note that this is not intended as a full survey of the literature and there are more \nstudies to be included below. Note also that this section does not discuss COVID -19 vaccines.  \n \n1. Acute Disseminated Encephalomyelitis (ADEM)  \na. “The evidence is inadequate to accept or reject a causal relationship between hepatitis B vaccine and \nADEM [acute disseminated encephalomyelitis].” Stratton, K., Ford, A., Rusch, E., Clayton, E. W., \nCommittee to Review Adverse Effects of Vaccines, & Instit ute of Medicine (Eds.). (2011). Adverse Effects \nof Vaccines: Evidence and Causality . National Academies Press (US). \nhttps://pubmed.ncbi.nlm.nih.gov/24624471/  \n \nb. “The evidence is inadequate to accept or reject a causal relationship between MMR vaccine and ADEM \n[acute disseminated encephalomyelitis].” Stratton, K., Ford, A., Rusch, E., Clayton, E. W., Committee to \nReview Adverse Effects of Vaccines, & Institute of M edicine (Eds.). (2011). Adverse Effects of Vaccines: \nEvidence and Causality . National Academies Press (US).  https://pubmed.ncbi.nlm.nih.gov/24624471/  \n \nc. “The evidence is inadequate to accept or reject a causal relationship between varicella vaccine and ADEM \n[acute disseminated encephalomyelitis].” Stratton, K., Ford, A., Rusch, E., Clayton, E. W., Committee to \nReview Adverse Effects of Vaccines, & Institut e of Medicine (Eds.). (2011). Adverse Effects of Vaccines: \nEvidence and Causality . National Academies Press (US).  https://pubmed.ncbi.nlm.nih.gov/24624471/  \n \nd. “The evidence is inadequate to accept or reject a causal relationship between influenza vaccine and ADEM \n[acute disseminated encephalomyelitis].” Stratton, K., Ford, A., Rusch, E., Clayton, E. W., Committee to \nReview Adverse Effects of Vaccines, & Institut e of Medicine (Eds.). (2011). Adverse Effects of Vaccines: \nEvidence and Causality . National Academies Press (US).  https://pubmed.ncbi.nlm.nih.gov/24624471/  \n \ne. “The evidence is inadequate to accept or reject a causal relationship between HPV vaccine and ADEM \n[acute disseminated encephalomyelitis].” Stratton, K., Ford, A., Rusch, E., Clayton, E. W., Committee to \nReview Adverse Effects of Vaccines, & Institute of M edicine (Eds.). (2011). Adverse Effects of Vaccines: \nEvidence and Causality . National Academies Press (US).  https://pubmed.ncbi.nlm.nih.gov/24624471/  \n \nf. “The evidence is inadequate to accept or reject a causal relationship between diphtheria toxoid –, tetanus \ntoxoid –, or acellular pertussis –containing vaccine and ADEM [acute disseminated encephalomyelitis].” \nStratton, K., Ford, A., Rusch, E., Clayton, E. W. , Committee to Review Adverse Effects of Vaccines, & \nInstitute of Medicine (Eds.). (2011). Adverse Effects of Vaccines: Evidence and Causality . National \nAcademies Press (US). https://pubmed.ncbi.nlm.nih.gov/24624471/    \n \ng. “The evidence is inadequate to accept or reject a causal relationship between meningococcal vaccine and \nADEM [acute disseminated encephalomyelitis].” Stratton, K., Ford, A., Rusch, E., Clayton, E. W., \nCommittee to Review Adverse Effects of Vaccines, & Inst itute of Medicine (Eds.). (2011). Adverse Effects \nof Vaccines: Evidence and Causality . National Academies Press (US). \nhttps://pubmed.ncbi.nlm.nih.gov/24624471/   \n \nh. “The evidence is inadequate to accept or reject a causal relationship between hepatitis A vaccine and \nADEM [acute disseminated encephalomyelitis].” Stratton, K., Ford, A., Rusch, E., Clayton, E. W., \nCommittee to Review Adverse Effects of Vaccines, & Instit ute of Medicine (Eds.). (2011). Adverse Effects \nof Vaccines: Evidence and Causality . National Academies Press (US).  \nhttps://pubmed.ncbi.nlm.nih.gov/24624471/  \n \ni. “ADEM typically appears with the abrupt onset of neurologic symptoms 2 to 30 days after the occurrence \nof a preceding infection or vaccination.” Noorbakhsh F., Johnson RT, Emery D., Power C. (2008). Acute \ndisseminated encephalomyelitis: clinical and pathogenesis features. Neurologic Clinics 26(3):759 -80. \nhttps://pmc.ncbi.nlm.nih.gov/articles/PMC7132764/   \n \nj. “The review focused on 23 cases linking acute disseminated encephalomyelitis (ADEM) to influenza \nvaccination, gathered from 19 comprehensive articles.” Mashkoor Y, Nadeem A, Fatima T, Aamir M, Vohra \nLI, Habib A, Khan A, Raufi N, Habte A. (2024). Neurological complications of influenza vaccination: \n58 \n navigating the spectrum with a focus on acute disseminated encephalomyelitis (ADEM).  Ann Med Surg \n(Lond). 86(2):1029 -1041. https://pubmed.ncbi.nlm.nih.gov/38333316/  \n \nk. “Post -vaccination ADEM has been associated with several vaccines such as rabies, diphtheria –tetanus –\npolio, smallpox, measles, mumps, rubella, Japanese B encephalitis, pertussis, influenza, hepatitis B, and the \nHog vaccine. We review ADEM with particular em phasis on vaccination as the precipitating factor.”  Huynh \nW, Cordato DJ, Kehdi E, Masters LT, Dedousis C. (2008) Post-vaccination encephalomyelitis: literature \nreview and illustrative case. J Clin Neurosci. 15(12):1315 -22. \nhttps://pmc.ncbi.nlm.nih.gov/articles/PMC7125578/   \n \n2. Acute Renal Failure  \na. “This is the fourth case report of acute renal failure after influenza vaccination in patients on statins therapy. \nThe case we describe could account for a [sic] underestimated, even if very rare, phenomenon.” Novati R, \nNebiolo PE, Galotto C, Mastaglia M, Manes M. (2014) Acute renal failure after influenza vaccination: a \ncase report.  J Prev Med Hyg. 55(1):31 -2. https://pubmed.ncbi.nlm.nih.gov/25916030/    \n \n3. Allergy  \na. “This study evaluated different dosage forms of aluminum adjuvant in generating allergic rhinitis animal \nmodels.“  Xi et al. (2014). Role of aluminum adjuvant in producing an allergic rhinitis animal model.  Genetics \nand Molecular Research 13(3):5173 -5181. https://pubmed.ncbi.nlm.nih.gov/25061742/   \n \n4. Alopecia  \na. “Adults receiving HBV had significantly increased odds ratios (OR) for…alopecia (OR = 7.2, p < 0.0001, \n95% CI = 3.2 - 20)…in comparison to the TCV [control] group. Minimal confounding or systematic error \nwas observed.” Geier DA, Geier MR. (2005). A case -control study of serious autoimmune adverse events \nfollowing hepatitis B immunization . Autoimmunity. 38(4):295 -301. \nhttps://pubmed.ncbi.nlm.nih.gov/16206512/    \n \n5. Amyotrophic lateral sclerosis (ALS)  \na. “The evidence is inadequate to accept or reject a causal relationship between HPV vaccine and ALS.” \nStratton, K., Ford, A., Rusch, E., Clayton, E. W., Committee to Review Adverse Effects of Vaccines, & \nInstitute of Medicine (Eds.). (2011). Adverse Effects of Vaccines: Evidence and Causality . National \nAcademies Press (US). https://pubmed.ncbi.nlm.nih.gov/24624471/  \n \nb. “Another issue we should consider in this case is the possibility that the HPV vaccine accelerated the ALS \npathogenesis and hastened the disease onset. The HPV vaccine contains a potent toll -like receptor 4 activator \nas an adjuvant, and recent animal studi es have shown that toll -like receptor 4 activation is involved in the \npathogenesis of ALS (9,10). Thus, at this time, it is too premature to conclude whether or not the HPV vaccine \nis completely safe in individuals with neurological conditions, and further  investigations are needed.  ” \nHikiami R, Yamakado H, Tatsumi S, Ayaki T, Hashi Y, Yamashita H, Sawamoto N, Tsuji T, Urushitani M, \nTakahashi R. (2018). Amyotrophic Lateral Sclerosis after Receiving the Human Papilloma Virus Vaccine: A \nCase Report of a 15 -year-old Girl.  Intern Med. 57(13):1917 -1919.  \nhttps://pmc.ncbi.nlm.nih.gov/articles/PMC6064690/    \n \n6. Anaphylaxis  \na. “The evidence convincingly supports a causal relationship between MMR vaccine and anaphylaxis.” \nStratton, K., Ford, A., Rusch, E., Clayton, E. W., Committee to Review Adverse Effects of Vaccines, & \nInstitute of Medicine (Eds.). (2011). Adverse Effects of Vaccines: Evidence and Causality . National \nAcademies Press (US). https://pubmed.ncbi.nlm.nih.gov/24624471/  \n \nb. “The evidence convincingly supports a causal relationship between varicella vaccine and anaphylaxis.” \nStratton, K., Ford, A., Rusch, E., Clayton, E. W., Committee to Review Adverse Effects of Vaccines, & \nInstitute of Medicine (Eds.). (2011). Adverse Effects of Vaccines: Evidence and Causality . National \nAcademies Press (US). https://pubmed.ncbi.nlm.nih.gov/24624471/    \n \n59 \n c. “The evidence convincingly supports a causal relationship between varicella vaccine and anaphylaxis.” \nStratton, K., Ford, A., Rusch, E., Clayton, E. W., Committee to Review Adverse Effects of Vaccines, & \nInstitute of Medicine (Eds.). (2011). Adverse Effects of Vaccines: Evidence and Causality . National \nAcademies Press (US). https://pubmed.ncbi.nlm.nih.gov/24624471/   \n \nd. “The  evidence  convincingly  supports  a  causal  relationship between hepatitis B vaccine and anaphylaxis \nin yeast sensitive individuals.” Stratton, K., Ford, A., Rusch, E., Clayton, E. W., Committee to Review \nAdverse Effects of Vaccines, & Institute of Medicine (Eds.). (2011). Adverse Effects of Vaccines: Evidence \nand Causality . National Academies Press (US). https://pubmed.ncbi.nlm.nih.gov/24624471/  \n \ne. “The evidence convincingly supports a causal relationship between tetanus toxoid vaccine and \nanaphylaxis.” Stratton, K., Ford, A., Rusch, E., Clayton, E. W., Committee to Review Adverse Effects of \nVaccines, & Institute of Medicine (Eds.). (2011). Adverse Effects of Vaccines: Evidence and Causality . \nNational Academies Press (US). https://pubmed.ncbi.nlm.nih.gov/24624471/    \n \nf. “The evidence convincingly supports a causal relationship between meningococcal vaccine and \nanaphylaxis.” Stratton, K., Ford, A., Rusch, E., Clayton, E. W., Committee to Review Adverse Effects of \nVaccines, & Institute of Medicine (Eds.). (2011). Adverse Effects of Vaccines: Evidence and Causality . \nNational Academies Press (US). https://pubmed.ncbi.nlm.nih.gov/24624471/    \n \ng. “The evidence favors acceptance of a causal relation between measles vaccine and anaphylaxis.” Institute \nof Medicine (US) Vaccine Safety Committee, Stratton, K. R., Howe, C. J., & Johnston, R. B., Jr. (Eds.). \n(1994). Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality . National \nAcademies Press (US). https://pubmed.ncbi.nlm.nih.gov/25144097/   \n \nh. “The committee concludes that the evidence favors acceptance of a causal relationship between HPV \nvaccine and anaphylaxis.” Stratton, K., Ford, A., Rusch, E., Clayton, E. W., Committee to Review Adverse \nEffects of Vaccines, & Institute of Medicine (Eds.). (2011). Adverse Effects of Vaccines: Evidence and \nCausality . National Academies Press (US). https://pubmed.ncbi.nlm.nih.gov/24624471/   \n \ni. “The evidence establishes a causal relation between DT, Td, and tetanus toxoid and anaphylaxis.” “The \nevidence establishes a causal relation between DT, Td, and tetanus toxoid and death from anaphylaxis.” \nInstitute of Medicine (US) Vaccine Safety Committee, Stratton, K. R., Howe, C. J., & Johnston, R. B., Jr. \n(Eds.). (1994). Adverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality . \nNational Academies Press (US). https://pubmed.ncbi.nlm.nih.gov/25144097/  \n \nj. “The evidence establishes a causal relation between hepatitis B vaccine and fatal anaphylaxis.” Institute of \nMedicine (US) Vaccine Safety Committee, Stratton, K. R., Howe, C. J., & Johnston, R. B., Jr. (Eds.). (1994). \nAdverse Events Associated with Childhood Vaccines: Evidence Bearing on Causality . National Academies \nPress (US). https://pubmed.ncbi.nlm.nih.gov/25144097/  \n \nk. “Non -physiological AEFI [adverse event following immunization], sometimes referred to as hyper -\nreactions, are rare, unexpected and more severe than physiological AEFI, and they tend to occur in \nimmunocompromised patients or patients allergic to vaccine com ponents []. The most severe AEFI are either \nallergic (anaphylaxis) or neurological (encephalopathy, encephalitis, neuritis), and can lead to hospitalization \nor death [].” Danova J, Kocourkova A, Celko AM. (2017). Active surveillance study of adverse events  \nfollowing immunisation of children in the Czech Republic . BMC Public Health. 17(1):167. \nhttps://pmc.ncbi.nlm.nih.gov/articles/PMC5292794/   \n \nl. “Six papers pertaining to fatal anaphylaxis following vaccination were found relevant.”  Palmiere C, \nTettamanti C, Scarpelli MP. (2017). Vaccination and anaphylaxis: a forensic perspective . Croat Med J. \n58(1):14 -25. https://pubmed.ncbi.nlm.nih.gov/28252871/   \n \nm. “We identified 13 anaphylaxis reports following MMR; 11 (84.6%) were serious. Seven reports met \nBrighton level 1 case definition of anaphylaxis. The other 6 were Brighton level 2. All had symptom onset \nwithin 24 hours of vaccination; most (10) within 1 hou r.” Sukumaran L, McNeil MM, Moro PL, Lewis PW, \nWiniecki SK, Shimabukuro TT. (2015). Adverse Events Following Measles, Mumps, and Rubella Vaccine in \n60 \n Adults Reported to the Vaccine Adverse Event Reporting System (VAERS), 2003 -2013 . Clin Infect Dis. \n60(10):e58 -65. https://pmc.ncbi.nlm.nih.gov/articles/PMC4447805/   \n \nn. “Comparison of adverse events in different ages following acellular anti -pertussis vaccines shows no \nsignificant differences in febrile reactions, seizures and allergic reactions, which almost evenly occur in both \nage groups.” Patterson J, Kagina BM, Gold M, Hussey GD, Muloiwa R. (2018). Comparison of adverse \nevents following immunisation with acellular and whole -cell pertussis vaccines: A systematic review.  \nVaccine. 36(40):6007 -6016. https://pubmed.ncbi.nlm.nih.gov/30143272/   \n \n7. Antiphospholipid syndrome (APS)  \na. “Successful induction of antiphospholipid syndrome (APS) in two different non -autoimmune prone mouse \nstrains …, was achieved by tetanus toxoid (TTd) hyperimmunization using different adjuvants … and \ndifferent adjuvant pretreatments. …  In this paper we have  explained our model of APS based on TTd \nhyperimmunization which supports the concept of the mosaic of autoimmunity.” L. Dimitrijevic et al. (2012). \nVaccine model of antiphospholipid syndrome induced by tetanus vaccine.  Lupus 21(2):195 -202. \nhttps://pubmed.ncbi.nlm.nih.gov/22235053/   \n \nb. “There are few reports of autoimmune diseases, such as rheumatoid arthritis and anti -phospholipid \nsyndrome after anti -tetanus vaccination. Herein, we describe four cases, of which we believe, show a clear \ntemporal relation between anti -tetanus vaccination and the appearance of dermatomyositis, systemic lupus \nerythematosus, type 1 diabetes mellitus and anti -phospholipid syndrome.” Ruhrman -Shahar N, Torres -Ruiz \nJ, Rotman -Pikielny P, Levy Y. (2017). Autoimmune reaction after anti -tetanus vaccination -descriptio n of \nfour cases and review of the literature . Immunol Res. 65(1):157 -163. \nhttps://pubmed.ncbi.nlm.nih.gov/27435706/   \n \nc. “We included in this review animal models for rheumatoid arthritis -like disease, for systemic lupus \nerythematosus -like disease, autoimmune thyroid disease -like disease, antiphospholipid syndrome, \nmyocarditis and others. All these models support the concept  of ASIA, as the Autoimmune (Auto -\ninflammatory) Syndrome Induced by Adjuvants.” Cruz -Tapias P, Agmon -Levin N, Israeli E, Anaya JM, \nShoenfeld Y. (2013). Autoimmune (auto -inflammatory) syndrome induced by adjuvants (ASIA) --animal \nmodels as a proof of concept . Curr Med Chem. 20(32):4030 -6. https://pubmed.ncbi.nlm.nih.gov/23992328/   \n \n8. Apnea  \na. “Infants in NICU had an increased incidence of sepsis evaluations and increased respiratory support and \nintubation after routine immunization.” DeMeo SD et al. (2015). Adverse Events After Routine Immunization \nof Extremely Low -Birth -Weight Infants.  JAMA Pediatr . 169(8):740 –745. \nhttps://pmc.ncbi.nlm.nih.gov/articles/PMC4523398/  \n \nb. “For infants in the NICU without apnea during the 24 hours immediately before immunization, younger \nage, smaller size, and more severe illness at birth are important predictors of postimmunization apnea.” Klein \net al. (2008). Risk Factors for Developing Apnea After Immunization in the Neonatal Intensive Care Unit.  \nPediatrics 121(3):463 –469. https://pubmed.ncbi.nlm.nih.gov/18310193/  \n \nc. “The majority of preterm infants tolerated immunizations with DTP and HibC without ill effects. However, \n12 (12%) infants experienced a recurrence of apnea, and 11 (11%) had at least a 50% increase in the number \nof apneic and bradycardic episodes in the 72  hours after immunization.” Sánchez PJ, Laptook AR, Fisher L, \nSumner J, Risser RC, Perlman JM. (1997). Apnea after immunization of preterm infants.  J Pediatr. \n130(5):746 -51. https://pubmed.ncbi.nlm.nih.gov/9152284/  \n \nd. “In hospitalized preterm infants, the odds of apnea within 48 hours were higher after 2 -month vaccinations \nvs after no vaccinations.”  Greenberg RG, et al. (2025). Apnea After 2 -Month Vaccinations in Hospitalized \nPreterm Infants: A Randomized Clinical Trial . JAMA Pediatr. 179(3):246 -254. \nhttps://pubmed.ncbi.nlm.nih.gov/39761016/   \n \n9. Arthritis/Arthropathy/Arthralgia   \n61 \n a. “The evidence favors acceptance of a causal relationship between MMR vaccine and transient arthralgia \nin women.” Stratton, K., Ford, A., Rusch, E., Clayton, E. W., Committee to Review Adverse Effects of \nVaccines, & Institute of Medicine (Eds.). (2011). Adverse Effects of Vaccines: Evidence and Causality . \nNational Academies Press (US). https://pubmed.ncbi.nlm.nih.gov/24624471/  \n \nb. “The evidence favors acceptance of a causal relationship between MMR vaccine and transient arthralgia \nin children.” Stratton, K., Ford, A., Rusch, E., Clayton, E. W., Committee to Review Adverse Effects of \nVaccines, & Institute of Medicine (Eds.). (2011). Adverse Effects of Vaccines: Evidence and Causality . \nNational Academies Press (US). https://pubmed.ncbi.nlm.nih.gov/24624471/  \n \nc. “The evidence is inadequate to accept or reject a causal relationship between MMR vaccine and chronic \narthralgia in women.” Stratton, K., Ford, A., Rusch, E., Clayton, E. W., Committee to Review Adverse \nEffects of Vaccines, & Institute of Medicine (Eds.). (2011). Adverse Effects of Vaccines: Evidence and \nCausality . National Academies Press (US). https://pubmed.ncbi.nlm.nih.gov/24624471/  \n \nd. “The evidence is inadequate to accept or reject a causal relationship between MMR vaccine and chronic \narthropathy in children.” Stratton, K., Ford, A., Rusch, E., Clayton, E. W., Committee to Review Adverse \nEffects of Vaccines, & Institute of Medicine (Eds .). (2011). Adverse Effects of Vaccines: Evidence and \nCausality . National Academies Press (US).  https://pubmed.ncbi.nlm.nih.gov/24624471/  \n \ne. “The evidence is inadequate to accept or reject a causal relationship between MMR vaccine and \narthropathy in men.” Stratton, K., Ford, A., Rusch, E., Clayton, E. W., Committee to Review Adverse Effects \nof Vaccines, & Institute of Medicine (Eds.). (2011). Adverse Effects of Vaccines: Evidence and Causality . \nNational Academies Press (US). https://pubmed.ncbi.nlm.nih.gov/24624471/  \n \nf. “The evidence is inadequate to accept or reject a causal relationship between varicella vaccine and onset \nor exacerbation of arthropathy.” Stratton, K., Ford, A., Rusch, E., Clayton, E. W., Committee to Review \nAdverse Effects of Vaccines, & Institute of Medicine (Eds.). (2011). Adverse Effects of Vaccines: Evidence \nand Causality . National Academies Press (US). https://pubmed.ncbi.nlm.nih.gov/24624471/  \n \ng. “The evidence is inadequate to accept or reject a causal relationship between hepatitis B vaccine and onset \nor exacerbation of psoriatic arthritis.” Stratton, K., Ford, A., Rusch, E., Clayton, E. W., Committee to Review \nAdverse Effects of Vaccines, & Institute of Medicine (Eds.). (2011). Adverse Effects of Vaccines: Evidence \nand Causality . National Academies Press (US). https://pubmed.ncbi.nlm.nih.gov/24624471/  \n \nh. “The evidence is inadequate to accept or reject a causal relationship between hepatitis B vaccine and onset \nor exacerbation of reactive arthritis.” Stratton, K., Ford, A., Rusch, E., Clayton, E. W., Committee to Review \nAdverse Effects of Vaccines, & Institute of Medicine (Eds.). (2011). Adverse Effects of Vaccines: Evidence \nand Causality . National Academies Press (US). https://pubmed.ncbi.nlm.nih.gov/24624471/  \n \ni. “The evidence is inadequate to accept or reject a causal relationship between hepatitis B vaccine and onset \nor exacerbation of rheumatoid arthritis.” Stratton, K., Ford, A., Rusch, E., Clayton, E. W., Committee to \nReview Adverse Effects of Vaccines, & Institute of Medicine (Eds.). (2011). Adverse Effects of Vaccines: \nEvidence and Causality . National Academies Press (US)  https://pubmed.ncbi.nlm.nih.gov/24624471/  \n \nj. “The evidence is inadequate to accept or reject a causal relationship between hepatitis B vaccine and onset \nor exacerbation of juvenile idiopathic arthritis.” Stratton, K., Ford, A., Rusch, E., Clayton, E. W., Committee \nto Review Adverse Effects of Vaccines, & Institute of Medicine (Eds.). (2011). Adverse Effects of Vaccines: \nEvidence and Causality . National Academies Press (US).  https://pubmed.ncbi.nlm.nih.gov/24624471/  \n \nk. “The evidence is inadequate to accept or reject a causal relationship between HPV vaccine and transient \narthralgia.” Stratton, K., Ford, A., Rusch, E., Clayton, E. W., Committee to Review Adverse Effects of \nVaccines, & Institute of Medicine (Eds.). (2011). Adverse Effects of Vaccines: Evidence and Causality . \nNational Academies Press (US). https://pubmed.ncbi.nlm.nih.gov/24624471/  \n \nl. “The evidence is inadequate to accept or reject a causal relationship between diphtheria toxoid –, tetanus \ntoxoid –, or acellular pertussis –containing vaccine and arthropathy.” Stratton, K., Ford, A., Rusch, E., Clayton, \n62 \n E. W., Committee to Review Adverse Effects of Vaccines, & Institute of Medicine (Eds.). (2011). Adverse \nEffects of Vaccines: Evidence and Causality . National Academies Press (US). \nhttps://pubmed.ncbi.nlm.nih.gov/24624471/   \n \nm. “The evidence is inadequate to accept or reject a causal relationship between influenza vaccine and onset \nor exacerbation of arthropathy.” Stratton, K., Ford, A., Rusch, E., Clayton, E. W., Committee to Review \nAdverse Effects of Vaccines, & Institute of Medicine (Eds.). (2011). Adverse Effects of Vaccines: Evidence \nand Causality . National Academies Press (US).  https://pubmed.ncbi.nlm.nih.gov/24624471/  \n \nn. “The Advisory Committee of Immunization Practices at the Centers for Disease Control and Prevention \nconcluded 3 years later that a causal relationship exists between arthritis and two vaccination combinations: \ndiphtheria -tetanus -pertussis (DTP) and measles -mumps -rubella (MMR).” Agmon -Levin N, Paz Z, Israeli E, \nShoenfeld Y. (2009). Vaccines and autoimmunity . Nat Rev Rheumatol. 5(11):648 -52. \nhttps://pubmed.ncbi.nlm.nih.gov/19865091/    \n \no. “We identified 15 reports of arthritis or arthralgia following MMR. All were in females, and onset ranged \nfrom 0 to 19 days postvaccination. One report was serious and involved a patient subsequently diagnosed \nwith rheumatoid arthritis.”  Sukumaran L, McNeil MM, Moro PL, Lewis PW, Winiecki SK, Shimabukuro \nTT. (2015). Adverse Events Following Measles, Mumps, and Rubella Vaccine in Adults Reported to the \nVaccine Adverse Event Reporting System (VAERS), 2003 -2013.  Clin Infect Dis. 60(10):e58 -65. \nhttps://pmc.ncbi.nlm.nih.gov/articles/PMC4447805/   \n \np. “Adults receiving HBV had significantly increased odds ratios (OR) for…arthritis (OR = 2.01, p < 0.0003, \n95% CI = 1.3 - 3.1)…in comparison to the TCV [control] group.” Geier DA, Geier MR. (2005). A case -\ncontrol study of serious autoimmune adverse events following hepatitis B immunization . Autoimmunity. \n38(4):295 -301. https://pubmed.ncbi.nlm.nih.gov/ 16206512/  \n \nq. “Recombinant hepatitis B vaccine may trigger the development of Rheumatoid Arthritis in MHC class II \ngenetically susceptible individuals.” Pope, J.E., Stevens, A., Howson, W., Bell, D.A. (1998). The \ndevelopment of rheumatoid arthritis after recombinant hepatitis B vaccination . J Rheumatol. \nhttps://pubmed.ncbi.nlm.nih.gov/9733447/   \n \nr. “Adults receiving HBV [Hepatitis B Vaccine] had significantly increased odds ratios (OR) \nfor…rheumatoid arthritis (OR = 18, p < 0.0001, 95% CI = 3.1 - 740)…in comparison to the [control] group. \nMinimal confounding or systematic error was observed.” Geier, D.A., Geier, M.R. (2005). A case -control \nstudy of serious autoimmune adverse events following hepatitis B immunization . Autoimmunity. \nhttps://pubmed.ncbi.nlm.nih.gov/ 16206512/   \n \n10. Asthma   \na. “The evidence is inadequate to accept or reject a causal relationship between LAIV [live attenuated \ninfluenza vaccine] and asthma exacerbation or reactive airway disease episodes in children younger than 5 \nyears of age.” Stratton, K., Ford, A., Rusch, E., Clayton, E. W., Committee to Review Adverse Effects of \nVaccines, & Institute of Medicine (Eds.). (2011). Adverse Effects of Vaccines: Evidence and Causality . \nNational Academies Press (US). https://pubmed.ncbi.nlm.nih.gov/24624471/  \n \nb. “The evidence is inadequate to accept or reject a causal relationship between LAIV [live attenuated \ninfluenza vaccine] and asthma exacerbation or reactive airway disease episodes in persons 5 years of age or \nolder.” Stratton, K., Ford, A., Rusch, E., Clayton, E. W., Committee to Review Adverse Effects of Vaccines, \n& Institute of Medicine (Eds.). (2011). Adverse Effects of Vaccines: Evidence and Causality . National \nAcademies Press (US). https://pubmed.ncbi.nlm.nih.gov/24624471/  \n \nc. “Among children with eczema, vaccine -associated aluminum was positively associated with persistent \nasthma (aHR 1.26 per 1 mg increase in aluminum, 95% CI 1.07, 1.49); a positive association was also \ndetected among children without eczema (aHR 1.19, 95% CI 1.14, 1.25).” Daley MF, Reifler LM, Glanz JM, \nHambidge SJ, Getahun D, Irving SA, Nordin JD, McClure DL, Klein NP, Jackson ML, Kamidani S, Duffy \nJ, DeStefano F. (2023).  Association Between Aluminum Exposure From Vaccines Before Age 24 Months and \n63 \n Persistent Asthma at Age 24 to 59 Months . Acad Pediatr. 23(1):37 -46. \nhttps://pubmed.ncbi.nlm.nih.gov/29458196/  \n \nd. “In this study, which only allowed for the calculation of unadjusted observational associations, higher ORs \nwere observed within the vaccinated versus unvaccinated group for developmental delays, asthma and ear \ninfections. Further study is necessary to und erstand the full spectrum of health effects associated with \nchildhood vaccination.” Hooker BS, Miller NZ. (2020). Analysis of health outcomes in vaccinated and \nunvaccinated children: Developmental delays, asthma, ear infections and gastrointestinal disorde rs. SAGE \nOpen Med. 8:2050312120925344. https://pubmed.ncbi.nlm.nih.gov/32537156/   \n \n11. Ataxia   \na. “The evidence is inadequate to accept or reject a causal relationship between MMR vaccine and ataxia.” \nStratton, K., Ford, A., Rusch, E., Clayton, E. W., Committee to Review Adverse Effects of Vaccines, & \nInstitute of Medicine (Eds.). (2011). Adverse Effects of Vaccines: Evidence and Causality . National \nAcademies Press (US). https://pubmed.ncbi.nlm.nih.gov/24624471/  \n \nb. “The evidence is inadequate to accept or reject a causal relationship between varicella vaccine and \ncerebellar ataxia.” Stratton, K., Ford, A., Rusch, E., Clayton, E. W., Committee to Review Adverse Effects \nof Vaccines, & Institute of Medicine (Eds.). (201 1). Adverse Effects of Vaccines: Evidence and Causality . \nNational Academies Press (US). https://pubmed.ncbi.nlm.nih.gov/24624471/  \n \nc. “The evidence is inadequate to accept or reject a causal relationship between diphtheria toxoid –, tetanus \ntoxoid –, or acellular pertussis –containing vaccine and ataxia.” Stratton, K., Ford, A., Rusch, E., Clayton, E. \nW., Committee to Review Adverse Effects of Vaccines, & Institute of Medicine (Eds.). (2011). Adverse \nEffects of Vaccines: Evidence and Causality . National Academies Press (US). \nhttps://pubmed.ncbi.nlm.nih.gov/24624471/  \n \nd. “550 notification records of adverse events after MMR vaccination at 15 mo of age have been registered, \nand a total of 41 notifications have included “gait disturbance”. This corresponds to a frequency of 8 per 100 \n000 doses of MMR vaccine used for 15 -mo-old children. The symptoms and signs are characteristic of \ncerebellar ataxia.” Plesner AM, Hansen FJ, Taudorf K, Nielsen LH, Larsen CB, Pedersen E. (2000). Gait \ndisturbance interpreted as cerebellar ataxia after MMR vaccination at 15 months of age: a follow -up study.  \nActa Paediatr. 89(1):58 -63. https://pubmed.ncbi.nlm.nih.gov/10677059/  \n \ne. “The report of most cases of ataxia within the first 6 weeks after vaccination (when the date of vaccination \nis known), reveals an unbalanced distribution of occurrence in this time period, with most cases reported in \nthe first two weeks. This may suggest that some cases of ataxia are triggered by vaccination and warrants \ncontinuous and careful analysis of such cases after vaccination.” Sheikh et al. (2012). Ataxia after \nVaccination in United States, a Report from the CDC/FDA Vaccine Adverse Event Reporting  System [1990 –\n2010] (P05.016) . Neurology. 78(Meeting Abstracts 1). \nhttps://www.neurology.org/doi/10.1212/wnl.78.1_supplement.p05.016  \n \nf. “Although immunization with meningococcal group C conjugate vaccines has been associated with several \nneurological side effects, acute cerebellar ataxia has not been previously reported. The authors describe a \ncase of a 12 -year-old girl exhibiting acute ce rebellar ataxia following meningococcal group C conjugate \nvaccination.” Cutroneo PM, Italiano D, Trifirò G, Tortorella G, Russo A, Isola S, Caputi AP, Spina E. (2014). \nAcute cerebellar ataxia following meningococcal group C conjugate vaccination.  J Child N eurol. 29(1):128 -\n30. https://pubmed.ncbi.nlm.nih.gov/23275434/   \n \n12. Autism   \na. “The  evidence is inadequate to accept or reject a causal relationship between diphtheria toxoid –, tetanus \ntoxoid –, or acellular pertussis –containing vaccine and autism.” Stratton, K., Ford, A., Rusch, E., Clayton, E. \nW., Committee to Review Adverse Effects of Vaccines, & Institute of Medicine (Eds.). (2011). Adverse \nEffects of Vaccines: Evidence and Causality . National Academies Press (US). \nhttps://pubmed.ncbi.nlm.nih.gov/24624471/  \n \n64 \n b. “The application of the Hill’s criteria to these data indicates that the correlation between Al in vaccines \nand ASD may be causal.” Tomljenovic L, Shaw CA. (2011). Do aluminum vaccine adjuvants contribute to \nthe rising prevalence of autism?  J Inorg Biochem. 105(11):1489 -99. \nhttps://pubmed.ncbi.nlm.nih.gov/22099159/  \n \nc. “In the following article we briefly review the literature on Al neurotoxicity and the use of Al salts as \nvaccine adjuvants and consider not only direct toxic actions on the nervous system, but also the potential \nimpact for triggering autoimmunity. Autoimm une and inflammatory responses affecting the CNS appear to \nunderlie some forms of neurological disease, including developmental disorders.” Shaw, C. A., Li, D., & \nTomljenovic, L. (2014). Are there Negative CNS Impacts of Aluminum Adjuvants Used in Vaccines  and \nImmunotherapy?  Immunotherapy, 6(10), 1055 –1071. https://pubmed.ncbi.nlm.nih.gov/25428645/  \n \nd. “There was a suggestion of increased ASD risk among children whose mothers received an influenza \nvaccination in their first trimester, but the association was not statistically significant after adjusting for \nmultiple comparisons, indicating that the findi ng could be due to chance. These findings do not call for \nchanges in vaccine policy or practice, but do suggest the need for additional studies on maternal influenza \nvaccination and autism.” Zerbo O, Qian Y, Yoshida C, Fireman BH, Klein NP, Croen LA. (2017 ). \nAssociation Between Influenza Infection and Vaccination During Pregnancy and Risk of Autism Spectrum \nDisorder . JAMA Pediatr. 171(1):e163609. https://pubmed.ncbi.nlm.nih.gov/27893896/   \n \ne. “The aluminium content of brain tissue in autism was consistently high…. The pre -eminence of \nintracellular aluminium associated with non -neuronal cells was a standout observation in autism brain tissue \nand may offer clues as to both the origin of the brain  aluminium as well as a putative role in autism spectrum \ndisorder.” Mold M, Umar D, King A, Exley C. (2018). Aluminium in brain tissue in autism . J Trace Elem \nMed Biol. 46:76 -82. https://pubmed.ncbi.nlm.nih.gov/29413113/   \n \nf. By applying Hill's criteria for establishing causality between exposure and outcome we investigated \nwhether exposure to Al [aluminum] from vaccines could be contributing to the rise in ASD prevalence in the \nWestern world. Our results show that: (i) childre n from countries with the highest ASD prevalence appear to \nhave the highest exposure to Al from vaccines; (ii) the increase in exposure to Al adjuvants significantly \ncorrelates with the increase in ASD prevalence in the United States observed over the last  two decades \n(Pearson r=0.92, p<0.0001); and (iii) a significant correlation exists between the amounts of Al administered \nto preschool children and the current prevalence of ASD in seven Western countries, particularly at 3 -4 \nmonths of age (Pearson r=0.89 -0.94, p=0.0018 -0.0248). The application of the Hill's criteria to these data \nindicates that the correlation between Al in vaccines and ASD may be causal. Because children represent a \nfraction of the population most at risk for complications following expo sure to Al, a more rigorous evaluation \nof Al adjuvant safety seems warranted. Tomljenovic L, Shaw CA. (2011). Do aluminum vaccine adjuvants \ncontribute to the rising prevalence of autism?  J Inorg Biochem. 105(11):1489 -99. \nhttps://pubmed.ncbi.nlm.nih.gov/22099159/   \n \n13. Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) (Shoenfeld’s syndrome)   \na. “In recent years, four conditions: siliconosis, the Gulf war syndrome (GWS), the macrophagic myofasciitis \nsyndrome (MMF) and post -vaccination phenomena were linked with previous exposure to an adjuvant... \nRelating to the current knowledge we would like to suggest to include these comparable conditions under a \ncommon syndrome entitled ASIA, ‘Autoimmune (Auto -inflammatory) Syndrome Induced by Adjuvants ’”.  \n(2011). Shoenfeld Y, Agmon -Levin N. 'ASIA' - autoimmune/inflammatory syndrome induced by adjuvants.  \nJ Autoimmun. 36(1):4 -8. https://pubmed.ncbi.nlm.nih.gov/20708902/   \n \nb. “We included in this review animal models for rheumatoid arthritis -like disease, for systemic lupus \nerythematosus -like disease, autoimmune thyroid disease -like disease, antiphospholipid syndrome, \nmyocarditis and others. All these models support the concept  of ASIA, as the Autoimmune (Auto -\ninflammatory) Syndrome Induced by Adjuvants.” Cruz -Tapias P, Agmon -Levin N, Israeli E, Anaya JM, \nShoenfeld Y. (2013). Autoimmune (auto -inflammatory) syndrome induced by adjuvants (ASIA) --animal \nmodels as a proof of concept . Curr Med Chem. 20(32):4030 -6. https://pubmed.ncbi.nlm.nih.gov/23992328/   \n \nc. “We have examined the neurotoxicity of aluminum in humans and animals under various conditions, \nfollowing different routes of administration, and provide an overview of the various associated disease states. \n65 \n The literature demonstrates clearly negative impacts of aluminum on the nervous system across the age span. \nIn adults, aluminum exposure can lead to apparently age -related neurological deficits resembling Alzheimer's \nand has been linked to this disease and  to the Guamanian variant, ALS -PDC. … In young children, a highly \nsignificant correlation exists between the number of pediatric aluminum -adjuvanted vaccines administered \nand the rate of autism spectrum disorders. Many of the features of aluminum -induced n eurotoxicity may arise, \nin part, from autoimmune reactions, as part of the ASIA syndrome.” Shaw CA, Tomljenovic L. (2013). \nAluminum in the central nervous system (CNS): toxicity in humans and animals, vaccine adjuvants, and \nautoimmunity . Immunol Res. 56(2 -3):304 -16. https://pubmed.ncbi.nlm.nih.gov/23609067/   \n \n14. Autoimmune Encephalitis  \na. “ These two cases highlight the potential for AE following the administration of the Shingrix® vaccine \nand underscore the importance of prompt recognition and aggressive immunotherapy to prevent morbidity \nand mortality.” Madani TA, Khoja AA, Abuzinadah AR,  Abbas GM, Alotaibi AA, Alshehri ZI, Madani ST. \n(2025). Post-vaccinal seronegative autoimmune encephalitis following recombinant zoster vaccination in \ntwo immunocompetent patients . J Infect Chemother. 31(6):102713. \nhttps://pubmed.ncbi.nlm.nih.gov/40254183/  \n \n15. Autoimmune Diseases (Generally)  \na. “Reported post -vaccination autoimmune diseases in the adult include SLE, rheumatoid arthritis (RA), \ninflammatory myopathies, multiple sclerosis (MS), Guillain -Barré syndrome (GBS), and vasculitis.” Orbach \nH, Agmon -Levin N, Zandman -Goddard G. (2010). Vaccines and autoimmune diseases of the adult.  Discov \nMed. 9(45):90 -7. https://pubmed.ncbi.nlm.nih.gov/20193633/   \n \nb. “More than 600 cases of illnesses, many with MS -like symptoms, of people who had received the \nrecombinant HBV vaccine, have been collected in France. A growing fraction of people who have been \nvaccinated against HBV claim to have experienced serious side e ffects. Their complaints cover a wide \nspectrum of diseases, among which many of an autoimmune nature and nervous system disorders. Those \ninclude rheumatoid arthritis, optic neuritis, and neurodegenerative disorders that resemble MS. The temporal \nassociatio n of multiple sclerosis (MS) with HBV vaccination has been reported on few occasions [22, 23]; \nneurological symptoms and signs, as well as magnetic resonance imaging documenting central nervous \nsystem (CNS) demyelinization have occurred days to weeks after  HBV vaccination.” Shoenfeld Y, Aron -\nMaor A. (2000). Vaccination and autoimmunity -'vaccinosis': a dangerous liaison?  J Autoimmun. 14(1):1 -\n10. https://pubmed.ncbi.nlm.nih.gov/10648110/   \n \nc. “The VAERS and PubMed (1966 -2003) were searched for autoimmune conditions including arthritis, \nrheumatoid arthritis, myelitis\n…[truncated]", "summary": "SENT VIA EMAIL     Advisory Committee on Immunization Practices     Centers for Disease Control and Prevention   acip@cdc.gov      Re:  Supplement to December 5, 2025 Presentation Titled Development of the U.S.   Childhood Vaccination Schedule: With a Focus on Suggested Improvements     To ACIP:     Please find herein additional sources for various slides for the  above -referenced presentation.  As  disclosed in that presentation, I am the Manag ing Partner of Siri & Glimstad LLP which has…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-december-04-05-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-12-04-05/02-siri-child-imz-schedule-508.pdf", "doc_date": "2025-12-04", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 98}
{"title": "01 Hoeg Danish vax schedule 508", "content": "Tracy Beth Høeg, M.D., Ph.D.\nFDA Ex Officio to ACIP\nSenior Advisor for Clinical Sciences\nOffice of the Commissioner (OC) &Center for Biologics Evaluation and Research (CBER)US Food and Drug Administration\nCore Childhood Vaccination \nSchedules: An International \nPerspective with focus on \nthe US & Denmark\n3\nDanish- US double \ncitizen\nMD (WI, USA- MCW), \nResidency UC DavisPhD -Epidemiology & \nPublic Health (U \nCopenhagen)\n4\n45 peer reviewed \npublications -last 5 \nyears focus on infectious disease \nepidemiology & \nvaccines\nBefore FDA was at \nMIT Sloan & practicing physician\n5\nCore Childhood \nVaccines – as of  \nJanuary 2025(assumes DTaP , \nHiB, IPV given \nseparately)\nXX, 202X 6Assumes individual rather than \ncombined DTaP -Hib -HepB -IPV \nvaccines given in US\nACIP April 2025-  US international outlier in yearly \nCOVID -19 vaccines for children\n7\nCore \nVaccines by Country as of January, 2025\n8\n\nImage Credit: Jonatan Pallesen 9\nCore \nChildhood Vaccines -As \nof January 2025\nIpsunember XX, 202X 10\nAluminum exposure \nin childhood\nCenter for Xxxxxx Xxxxx Xxxxxxxxxxxxxxxxxx\n•Assumes individual \nrather than combined DTaP -\nHib-HepB -IPV \nvaccines given in US\n•What is the “safe” bolus dose of parenteral aluminum in infancy?\n11\nWhat do we owe to our children?\nScience -based recommendations\n•Understand potential for absolute benefit in low \nrisk populations\n•Understand the limitations in our knowledge about adverse effects\n•Perform proper randomized, placebo -controlled \nstudies\n•Continually monitor safety and update our recommendations based on evolving knowledge\n•Vaccines treated like all medical products; may not be right for all children\n12\nWhat do we owe to our children?\nAvoid overmedicalizing childhood\n•Time in pediatricians’ offices can be spent \ndifferently\n•Less focus on medical products; more focus on healthy living\n•Decreases overdiagnosis and overtreatment\n13\nWhat do we owe to our children?\nRecommendations based on \ndata and not politics\n•Manipulating data for political \nreasons can be deadly\n•Neo-Lamarkism /acquired genetics\n•Silencing of opposing views\n•Resulted in the death of potentially millions in the Chinese famine\n14\nDeaths \ndue to \npolio, measlesDeaths and injuries due \nto vaccines\n15\nUSA - Political Polarization\nDenmark\n•Multi -party system\n•Culture of Debate\n•Transparent decision making\n•Research culture (RCTs)\n•Extensive documentation of \ndecision making about \nvaccines\n•Acknowledge Unknowns\n•Promptly reverse \nrecommendationsHigher level of trust in Public Health Authorities\nUndeniably a healthier \npopulation\n16\n\nDoes the US \nhave a good \ntrack record in \nterms of child \nhealth?\n17\nHealth Conditions -mental health disorders\nSource: IHME -GHDx  18\n\nBecause the US has a larger high- risk population, \nshould the core childhood vaccination schedule be \nlarger  ?\n•Should healthy children in the US receive different \nvaccines than healthy children in Denmark?\n•Root cause of diseases\n19\nCore Childhood \nVaccines -As of \nJanuary 2025\n20What can we learn from \nother countries?\nWhy do the US and Denmark have \nsuch different core vaccination schedules?\nMisconception:\n Because of differences in disease \nprevalences\n21\nHow do incidences and prevalences of \ndiseases compare?\nUS vs Denmark\nHepatitis B: \nincidence in mothers & prevalence \nof chronic Hepatitis B\nhttps://journals.lww.com/ajg/fulltext/2020/09000/prevalence_of_chronic_hepatitis_b_virus_infection.20.aspx\nhttps://www.cdc.gov/hepatitis -b/hcp/perinatal -provider- overview/index.html#cdc_generic_section_7 -infection -rates -and -\ntrend\nClinical Overview of Perinatal Hepatitis B | Hepatitis B | CDC\nEfficacy of Selective Antenatal Screening for Hepatitis B Among Pregnant Women in Denmark: Is Selective Screening Still an \nAcceptable Strategy in a Low -endemicity Country?: Scandinavian Journal of Infectious Diseases: Vol 35, No 6 -7 XX, 202X 23\nIncidence of \nMeningococcal Disease in \n2023\nhttps://www.cidrap.umn.edu/meningitis/cdc- data -show -sharp -rise -rates -meningococcal -disease .\nhttps://en.ssi.dk/surveillance -and -preparedness/surveillance -in-denmark/annual- reports -on-disease -\nincidence/m/meningococcal -disease -202324•<5/million in both the US and \nDenmark\n\nUSA and Denmark Meningococcal Incidence over time\nhttps://www.cdc.gov/acip/downloads/slides -2024 -10-23-24/01 -mening -Loehr- 508.pdf\nhttps://ugeskriftet.dk/videnskab/vaccination- til-forebyggelse -af-meningokoksygdom\n25\n\nThere has been an increase in Measles Cases in \nthe US and Europe\nhttps://statistik.ssi.dk/sygdomsdata#!/?sygdomskode=M\nEAS&xaxis=Aar&show=Graph&datatype=Individual 26\nMeasles Cases by Vaccination Status in Europe\nhttps://www.ecdc.europa.eu/sites/default/files/documents/\nMEAS -AER -2024-Report.pdf27\n\nMeasles Cases in Denmark Over Time\nIpsunember XX, 202Xhttps://statistik.ssi.dk/sygdomsdata#!/?sygdomskode=MEA\nS&xaxis=Aar&show=Graph&datatype=Individual28\nVaccination \nRates by Age  5 in 2024\nCDC. Vaccination Coverage and Exemptions among Kindergartners.  2025.\nhttps://www.ssi.dk/vaccinationer/tilslutning -til-bornevaccinationsprogrammet -2024 29\n2024 MMR vaccination \nrates by state\nThe estimated critical \nminimum vaccination threshold to prevent measles outbreaks is around 90% \nhttps://publichealth.jhu.edu/sites/default/files/2024 -\n09/Measles -Risk -Assessment-\nMethodology_9.19.24.pdf\nIpsunember XX, 202X Center for Xxxxxx Xxxxx Xxxxxxxxxxxxxxxxxx 30\n\nNovember 2025\n31\nWhich countries \nhave or are at risk \nof loss of measles elimination \nstatus?\n32Current numbers - December 2025\nWhen and why do \ncitizens not trust \ncore childhood \nvaccination \nrecommendations?\n33Current numbers\nRubella\n•Rubella can cause congenital rubella syndrome \n•Has a community immunity threshold of 83 -85% \n•Some pockets of America and entire states, such as \nIdaho and Wisconsin, with average vaccination rates \nbelow this, at risk of rubella outbreaks. \nOtani N, Shima M, Ueda T, Nakajima K, Takesue  Y , Yamamoto T, Okuno T. Changes in the Epidemiology of Rubella: The Influence of Vaccine -Introducing Methods and COVID -\n19. Vaccines (Basel). 2023 Aug 12;11(8):1358. doi: 10.3390/vaccines11081358. PMID: 37631927; PMCID: PMC10458369.\nhttps://www.kff.org/medicaid/kindergarten -routine -vaccination- rates -continue -to-\ndecline/#:~:text=While%20measles%20has%20been%20officially,of%20an%20outbreak%20is%20higher34\nTrust in US \nhealthcare decreased from 72% to 40%\n35\n\nTrust \ndecreased from 72% to 40%\nIpsunember XX, 202X 36\n\nSchool based \nvaccine mandates?\n37\nFocus on Denmark\nThe Current Core Childhood Vaccination Schedule\n38\n\nDenmark Core Childhood Vaccines\n39\n\nCore Vaccines \nby Country as of January, 2025\n40\n\nEvolution of the \nCore Vaccine Schedule in USA\n41\nImage Credit: Jonatan Pallesen 42\nDanish Decision \nMaking about \nChildhood \nVaccines \nExamples of Child vaccines that were never or are no longer on the schedule43\nCOVID -19 Vaccine\nDenmark was the first high income \nnation to remove the COVID -19 vaccine \nfrom childhood schedule\nAhead of the international curve\n44\nHead of Danish Ministry of health stating in June of \n2022 that vaccinating children for COVID- 19 was a \nmistake\nDirector of the Danish Health Authority: https://nyheder.tv2.dk/samfund/2022 -06-22-set -i-bakspejlet -fik-vi-ikke -meget -ud-af-at -vaccinere -\nboernene -erkender -brostroem 45\nInfluenza Vaccine: \nintroduction for all \nchildren ages 2- 6 \nin 2021 was \nreversed in 2023\n46\nPandemrix Vaccine History\n•2009 H1N1 Pandemic Influenza \nvaccine\n•Side effects and narcolepsy Coverup/delayed reporting\n•Never recommended for children in Denmark\n•Now essentially of all Europe does not recommend seasonal influenza vaccine as core childhood vaccine\n•1300 people with narcolepsy, mostly children\n47\n\nHepatitis B Vaccine \n•Hvis man indfører en vaccine, \nsom nogle vil opfatte som \nmindre væsentlig , vil dette  \nkunne  påvirke den generelle \nholdning  til vaccination i \nnegative retning . \n•Resultatet heraf  kunne  være , at \ndet allerede eksisterende \nprogram opnår lavere \ntilslutning  i fremtiden . \nhttps://www.sst.dk/ -\n/media/Udgivelser/2004/hepatitis_b_180204, -d-,pdf.ashx48\n\nHepatitis B Vaccine \n•If one includes a vaccine which \nsome consider less important, \nit could negatively affect the view of vaccines in general.\n•The result of this could be that \nthe current [vaccination] \nprogram would have lower uptake.\nhttps://www.sst.dk/ -\n/media/Udgivelser/2004/hepatitis_b_180204, -d-,pdf.ashx49\n\nHepatitis B Vaccine: Targeted Program \nhttps://www.eurosurveillance.org/cont\nent/10.2807/esw.10.44.02827-enhttps://www.ssi.dk/vaccinationer/risikogrupper/personer -med -sarlig- risiko -\nfor-hepatitis -b-\nsmitte#:~:text=Nogle%20grupper%20har%20dog%20en,Dag%200%20(evt.50•Substantial costs of hep B \nvaccine coverage & low opportunity for benefit \n•Population -wide \nvaccination could not be justified from a health economics perspective\n•List of high risk groups which have vaccination coverage\n\nMeningococcal Vaccine\nhttps://ugeskriftet.dk/videnskab/vaccination-til -\nforebyggelse -af-meningokoksygdom51“Weekly writings for physicians”\n\nMeningococcal Vaccine\nhttps://ugeskriftet.dk/videnskab/vaccination-til -\nforebyggelse -af-meningokoksygdom52•Opportunity for benefit among \nnon high risk children is very low\n•Uncertainty about effectiveness\n•Adding additional vaccines to \nthe core vaccine list may cause \nsome parents to opt out of other vaccines\n•If the vaccine causes fevers in infant when given with other vaccines, this could have  \nnegative consequences for \nphysicians and parents\n\nMeningococcal Vaccine \nhttps://ugeskriftet.dk/videnskab/vaccination-til -\nforebyggelse -af-meningokoksygdom53\n•List of high risk situations\n•Asplenia\n•Compliment deficiency\n•Receiving Eculizumab (causes \ncompliment deficiency)\n•Travel to high prevalence regions\n•Meningococcal outbreak\n•Required for study in the US\n•Can be considered for student dormitory conditions \n\nRotavirus: rationale for not including \nin Child Vaccination Schedule\n•232 page document in Danish \ndescribing the decision\n•Will be reviewed again in the near future\n•It has until now been the message of the Danish Ministry of Health that Denmark not introduce vaccines into the child vaccination schedule just because it is an option\n•The Danish child vaccination program has… a goal of protecting children from infections that can be either deadly or have long term health consequences•Infection with rotavirus essentially never results in death or chronic consequences in a country like Denmark\n•Literature review has not shown that this vaccine has an effect on children’s mortality\nhttps://www.sst.dk/ -/media/Udgivelser/2012/Vaccination -mod -\nrotavirus ---en -medicinsk -teknologivurdering/Vaccination-mod -\nrotavirus -%E2%80%93-en -medicinsk -teknologivurdering.ashx54\nVaricella Vaccine\nCons\n•Worry that natural immunity is \nstronger (they cite data supporting)\n•Only 4% of genera/family physicians would recommend the vaccine to healthy children\n•Insufficient data about long term effects \n•Pros\n•Denmark has a very low rate of stay -\nat-home parents and they would \nmiss less work\nhttps://www.speam.dk/files/21/skoldkoppevaccine_i_danm\nark.pdf .55\n\nVaricella Vaccine\nCons\n•Worry that natural immunity is \nstronger (cite data supporting)\n•Only 4% of family physicians would recommend the vaccine to healthy children\n•Insufficient data about long term effects \nPros\n•Denmark has a very low rate of stay -at-home parents and they \nwould miss less work\nhttps://www.speam.dk/files/21/skoldkoppevaccine_i_danm\nark.pdf .56•bekymring  om, at immuniteten  er\n•svagere  efter  vaccine.\n•4% af de praktiserende læger synes at raske børn skal vaccineres mod skoldkopper,\n•Fortsat utilstrækkelige data på langtidseffekten\n•Gevinsten i Danmark kan være større end for mange andre lande, da andelen af hjemmegående mødre/fædre er lavere.\n\nRSV Long Acting Monoclonal Antibodies\n•Unfavorable imbalance in all cause mortality in all \nfour phase 3 randomized trials of standard dose \n57\n\nIpsunember XX, 202X 58\nDanish Child Vaccination Benefits\n•Increase Trust in and Focus on Core Childhood Vaccines\n•Based on thorough, transparent decision making and continually \nupdated and debated\n•Prevent outbreaks of most deadly vaccine preventable diseases\n•Equipoise=Opportunity for research\n•Re-evaluate the evidence base for vaccines not currently on core \nchildhood vaccine schedule in Denmark with randomized trials\n•Monitor Diseases such as Rotavirus; may be larger opportunity for \nabsolute benefit in the US population\n59\nDanish Vaccination Schedule Benefits\n•Make more time for addressing overall health at doctors' \nappointments/spend less time in the healthcare system/decrease \nthe medicalization of childhood\n•Opportunity to better define high risk groups to target\n•Improve informed consent\n•Minimize coercion\n60\nQuestions about Adopting the \nDanish Schedule in the US\n•Would it be appropriate to stop Varicella vaccine given high \nvaccination uptake and chance of increasing average age of \nchickenpox\n•Perform thorough, updated Risk -Benefit analysis of evidence for 2 \ndoses of HPV in girls and boys?\n61\nQuestions about Adopting the \nDanish Schedule in the US\n•Would it be appropriate to stop Varicella vaccine given high \nvaccination uptake and chance of increasing average age of \nchickenpox\n•Perform thorough, updated Risk -Benefit analysis of evidence for 2 \ndoses of HPV in girls and boys?\n62\n\nFIN", "summary": "Tracy Beth Høeg, M.D., Ph.D. FDA Ex Officio to ACIP Senior Advisor for Clinical Sciences Office of the Commissioner (OC) &Center for Biologics Evaluation and Research (CBER)US Food and Drug Administration Core Childhood Vaccination  Schedules: An International  Perspective with focus on  the US & Denmark 3 Danish- US double  citizen MD (WI, USA- MCW),  Residency UC DavisPhD -Epidemiology &  Public Health (U  Copenhagen) 4 45 peer reviewed  publications -last 5  years focus on infectious…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-december-04-05-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-12-04-05/01-Hoeg-Danish-vax-schedule-508.pdf", "doc_date": "2025-12-04", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 63}
{"title": "01 Griffin aluminum adjuvants 508", "content": "Considerations and Query for the\n Advisory Committee for Immunization Practices\nPresented by Dr. Evelyn Griffin, MD, FACOG, IFMCP  \nChild/Adolescent Immunization Schedule Work Group\nVaccinations during Pregnancy Work Group \nHPV Work GroupVaccines \nand Aluminum Adjuvants\nBackground\nChild/Adolescent Immunization Schedule Work Group Discussion\nObjectives\nACIP Charter: provide “advice and guidance to the \nDirector of the CDC regarding the use of vaccines and \nrelated agents” \n•Consideration of an ACIP Adjuvant Work Group\n•Educational forum \nSome categories of vaccines: \n•live attenuated (ie MMR), killed/subunit/recombinant, gene therapy -based \nMany ingredients in vaccine products:\n•Antigens\n•Adjuvants\n•Preservatives \n•Stabilizers\n•Surfactants\n•Residuals\n•Diluents\n•(Adulterants in rare cases)Vaccine Overview \nSome categories of vaccines: \n•live attenuated (ie MMR), killed/subunit/recombinant, gene therapy -based \nMany ingredients in vaccine products:\n•Antigens\n•Adjuvants\n•Preservatives \n•Stabilizers\n•Surfactants\n•Residuals\n•Diluents\n•(Adulterants in rare cases)\nEach vaccine is unique, and each component may contribute to risk, safety, efficacy, \nand effectiveness of a vaccine final drug product.Vaccine Overview \nWhat is an Adjuvant? \n•An adjuvant is any substance or compound added to a vaccine to enhance the \nbody’s immune response to the antigen (portion that mimics the pathogen).\n•It stimulates the innate and adaptive immune responses to augment vaccine efficacy and longterm effectiveness.\nVaccine Overview:\nAdjuvants \n•Typically, only killed/subunit/recombinant – type vaccines include adjuvants.\n•A large portion of the childhood and adolescent vaccine schedule and \nvaccines given during pregnancy are formulated with adjuvants. \nDoes the FDA approve adjuvants?\n•FDA approves final drug products, it does not approve adjuvants.  \n•There are no “FDA approved” adjuvants.Vaccine Overview:\nAdjuvants \n•Typically, only killed/subunit/recombinant – type vaccines include adjuvants.\n•A large portion of the childhood and adolescent vaccine schedule and \nvaccines given during pregnancy are formulated with adjuvants. \nAre there Different Types of Adjuvants?\n•Some adjuvants and adjuvant categories:\n•Aluminum salts \n•Oil-in-water emulsions\n•Liposome-based\n•Toll-Like Receptor (TLR) agonists\n•Saponin (plant) -based\n•Most killed/subunit/recombinant vaccines rely on aluminum salt -based \nadjuvants (ABA).  Since the 1920s, these have been the most widely used \nadjuvants in FDA-licensed human vaccines.\n•Examples of ABA:  aluminum oxyhydroxide (Alhydrogel®) and aluminum hydroxyphosphate (Adju-Phos®)\nAluminum and Aluminum Salt Adjuvants\n\nThe only published/peer -reviewed study of aluminum blood levels observed in \ninfants after aluminum -adjuvant containing vaccine administration.\n•Sample size (n= 15), serum aluminum levels measured before and 24 hours \nafter vaccination \n•No significant detectable mean increase at 24h relative to pre-vax levels\n•No long -term data, or organ distribution dataBiodistribution and Pharmacokinetics\nMovsas et al. 2013\nCurrent US Aluminum Exposure Limits\nUS Agency for Toxic Substances and Disease Registry (ATSDR) determined a \nMinimum Risk Level (MRL) for orally ingested aluminum:\n•Oral MRL ≈ 1 mg (1,000 mcg) Al/kg/day based on animal data\n•Assumes  ~0.1% oral absorption\n•Converted to an injected -equivalent threshold,     \nthis approximates 1 mcg/kg/day \nCurrent US Aluminum Exposure Limits\nThe U.S. Code of Federal Regulations (21 CFR 610.15(a))  limits aluminum in \nvaccines to ≤0.85 mg (850mcg) per dose, regardless of age group.\n•Flarend et al., 1997: Doses up to 850 mcg total IM aluminum (including aluminium hydroxide and aluminium phosphate adjuvants) in rabbits resulted in transient blood level increases that resolved quickly, with no acute or chronic adverse effects observed. \n•This is still the current FDA -accepted benchmark for human vaccine adjuvant \ndosing.\n•Masson et al., 2018 examined the limitations of using the Flarend study as a basis for regulatory threshold setting.\nWhy Focus on Aluminum Dose in Vaccines?\n•Infants receive multiple aluminum- containing vaccines in a single visit under the \ncurrent schedule.\n•Dose per kilogram body weight is far higher in early infancy than in adults.\n•Neonatal kidneys, blood –brain barrier, and detoxification systems are immature.\nWhy Focus on Aluminum Dose in Vaccines?\n•Infants receive multiple aluminum- containing vaccines in a single visit under the \ncurrent schedule.\n•Dose per kilogram body weight is far higher in early infancy than in adults.\n•Neonatal kidneys, blood –brain barrier, and detoxification systems are immature.\n*There are similar considerations for children \n  and fetuses through pregnancy vaccination.\nMultiple Aluminum Adjuvanted Vaccine Doses \nResults in Cumulative Aluminum Exposure \nThe administration of one dose \neach of Prevnar 20, PedvaxHIB, \nEngerix -B, and Infanrix at one \nvisit delivers 1,225 mcg  of \naluminum.   \nPCV, Hib, HepB, and DTaP \nvaccines are administered multiple times by 6mo of age. \nThe rate at which aluminum \nfrom vaccines migrates from human muscle to the bloodstream is not known.\nVaccine Selection Can Double Aluminum \nExposure on the Same Schedule\n\n\"Term infants with normal renal function may also be at risk because of their \nrapidly growing and immature brain and skeleton, and an immature blood -\nbrain barrier. Until they are 1 to 2 years old, infants have lower glomerular filtration rates than adults, which affects their kidney function. The agency is concerned that young children and children with immature renal function are at a higher risk resulting from any exposure to aluminum.”\nCited in the Federal RegisterUS FDA Child Health Concerns, June 2003\nAluminum Biodistribution\nExperimental and clinical data suggest intramuscular injected aluminum \nand aluminum salts can persist at the injection site, then migrate via immune cells to liver, spleen, and other organs including the brain.\n\"The distribution profile of aluminium \nto tissues was the same for both adjuvants (AH and AP) kidney > spleen > liver > heart > lymph node > brain.\"\nGherardi RK et al\nMacrophagic myofasciitis (MMF)\n•Muscle biopsies show aluminum- containing macrophages in \ngranulomas at  prior IM vaccination injection sites (MMF lesions). \n•Symptoms in many MMF patients: chronic myalgias, fatigue, and \ncognitive difficulties.\n•Causal link between injected aluminum or aluminum salts  (aluminum oxyhydroxide) to systemic symptoms is not universally accepted.\n•Demonstrates long -term persistence of aluminum in human tissue.Persistence and Macrophagic Myofasciitis \n•Exley and Mold, 2019: Aluminum in postmortem brain tissue of neurological \npatients, reflecting cumulative environmental exposure\n•Shoenfeld and Agmon- Levin, 2011: Auto Immune/Inflammatory Syndrome \nInduced by Adjuvants\n•Shaw and Tomljenovic, 2014: aluminum neurotoxicity\n•Daley et al., 2023: Association between aluminum exposure from vaccines before age 24 months and persistent asthma at age 24 to 59 Months\n•Emerging research in mechanisms of aluminum oxidative stress: mitochondrial dysfunction, and impaired energy metabolism, pro -inflammatory effects and \nmicroglial activation, promotion of amyloidogenesis and disruption of metal homeostasis (i.e. iron)Aluminum Based Adjuvants: \nBiocompatible and Always Well Tolerated?\nAluminum Adjuvant Toxicology: \nData Gaps and Ambiguity\n•Currently available infant safety assessments rely on a small number of \ntoxicokinetic studies and modeled assumptions.\n•No long -term human studies tracking vaccine- derived aluminum kinetics in infants \nor children have been published.\n•Critical reviews challenge absorption factors and clearance assumptions in influential models (e.g., Mitkus 2011)\n•No large, prospective, well- controlled studies comparing neurodevelopmental or \nautoimmune outcomes by cumulative aluminum dose have been performed or \npublished.\n•No established safe dose of injected aluminum for fetuses, neonates and preterm \ninfants has been established.\n•Existing toxicology and pharmacokinetic data are too sparse and model- dependent \nto support definitive conclusions of safety at current cumulative doses.\nQuery for ACIP\nHow should ACIP continue to assess effectiveness and safety \nof adjuvants in currently authorized vaccines on the schedule \n(childhood/adolescent, adult, and vaccines during pregnancy), \nand related implications of the entire schedule?\nAdditional discussion\n•Should multiple aluminum- containing vaccines be administered on the same \nday in early infancy?\n•Should lower- aluminum formulations and spacing strategies be preferred \nwhen possible?\n•What research is needed to define a genuinely evidence- based safety \nmargin for injected aluminum?\n•What prudent policy would reduce peak and cumulative aluminum exposure \nin the most vulnerable while urgent research gaps are addressed?\nAcknowledgement & Invitation\nFor Collaboration", "summary": "Considerations and Query for the  Advisory Committee for Immunization Practices Presented by Dr. Evelyn Griffin, MD, FACOG, IFMCP   Child/Adolescent Immunization Schedule Work Group Vaccinations during Pregnancy Work Group  HPV Work GroupVaccines  and Aluminum Adjuvants Background Child/Adolescent Immunization Schedule Work Group Discussion Objectives ACIP Charter: provide “advice and guidance to the  Director of the CDC regarding the use of vaccines and  related agents”  •Consideration of an…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-december-04-05-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-12-04-05/01-Griffin-aluminum-adjuvants-508.pdf", "doc_date": "2025-12-04", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 28}
{"title": "MMRV vaccine safety summary 508", "content": "Rapid Systematic Review of the Safety of MMRV Vaccine  \nA. Background  \nThe measles -mumps -rubella -varicella (MMRV) vaccine (ProQuad, Merck) was licensed in the \nUnited States in 2005 for use in children 12 months through 12 years of age. While not licensed \nfor use in the United States, Priorix -Tetra, a MMRV vaccine manufactured by GlaxoSmithKline , \nfirst received licensing in some European countries in 2006, and in Canada in 2007.  Both \nProQuad and Priorix -Tetra are tetravalent vaccines with similar measles, mumps, rubella and \nvaricella viral strain composition. [1]  Henceforth, any reference to MMRV in this report refers to \nProQuad, unless otherwise specified.  \nIn 2006, the Advisory Committee on Immunization Practices (ACIP) noted that use of \ncombination vaccines, like MMRV, was preferred over separate injections of equivalent component vaccines (e.g., MMR vaccine and varicella vaccine  [MMR+V] ).[2]  Post- licensure \nsafety surveillance data indicated an increased risk for febrile seizures following the administration of the first dose of MMRV among children aged 12- 23 months compared to \nthose receiving separate MMR and varicella vaccines. [3]  Based on this data, ACIP and the \nCenters for Disease Control and Prevention updated its guidance to note that the first dose of \nMMR and varicella vaccines are preferred to be given separately in this age group, but MMRV \nmay be used as a first dose in chi ldren aged 12 -47 months based on parent or caregiver \npreference. [4]  Given the importance of maintaining a thorough awareness and assessment of \nMMRV vaccine safety publications, we propose a  review of the literature assessing  MMRV \nvaccine safety to inform the public and healthcare providers, and aid in public health policy discussions.   \nB. Methods  \nB.1. Key Question Development  \nThe below question is formulated according to the P I/ECO(ST)  strategy, and for this review, \nthose elements include and are not limited to  those identified in Table 1.   \n1. For children aged 12 months to 12 years, what is the safety of MMRV vaccine?   \nTable 1 \nPI/ECO(ST) Criteria for Key Question  \nPI/ECO(ST)  \nElement   Criteria   \nPopulation  Pediatric population that includes:   \no Infants and toddlers aged 12 months – 23 months   \no Young children and children aged 12 months – 12 years   \nIntervention or \nExposure  MMRV vaccination. Including ProQuad, Priorix -Tetra, and brand \nunspecified.  \nComparator (if \napplicable)  Any or  none  \nOutcome(s)  Adverse events   \nPI/ECO(ST)  \nElement   Criteria   \nAdverse outcomes   \nSafety outcomes  \nSide effects   \nSetting  Any  \nTime Frame  Any publication years  \nB.2. Literature Search  \nA CDC informationist (J.T.) developed search strategies from the Key Question and PI/ECO \ncriteria, and performed the search in MEDLINE, EMBASE, CINAHL, and Cochrane Library from the start of each database to August 1, 2025. Search strategies and results ar e provided in \nTable 3  in the Appendix . \nB.3. Study Selection \nResults of the literature searches were uploaded into EndNote 21 (Clarivate Analytics©, Thomson Reuters, New York, NY, USA), duplicate records were removed, and unique titles and abstracts were uploaded to Covidence (Veritas Health Innovation Ltd., Melbourne, VIC, Australia) where a second round of deduplication was conducted. Three reviewers (JR, EQ, JS) \nindependently screened all titles and abstracts and removed irrelevant references; \ndisagreements were resolved by consensus . Relevant full texts were scre ened independently \nby three reviewers (JR, EQ, JS); disagreements were resolved by consensus. All studies were screened according to the pre -identified exclusion criteria below, and results of the study \nselection process are provided in Figure 1 . \n Criteria for excluding studies from the literature review include:  \n1. No full text available;\n  \n2. Not available in English;  \n3. Pre-licensure clinical trials;  \n4. Not relevant to key question;  \n5. No primary data  or analysis,  or secondary data not systematically collected;  \n6. Insufficient methodologic reporting (i.e., meeting abstract or poster);  \n7. Study population includes participants <12 months or >12 years of age; or  \n8. Indeterminate age range of study population receiving vaccine.  \n  \n  \n   Figure 1. Results of the Study Selection Process  \n \n \n \n \n \n \n   \n \n \n \n \n  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n  \n \n \n \n \n  \nIdentification  \nStudies screened (n = 326)  \nStudies sought for retrieval (n = 117 ) \nStudies assessed for eligibility (n = 117 )     References removed (n = 8)   \nDuplicates identified manually (n = 8 ) \nDuplicates identified by Covidence (n = 0 )  \nMarked as ineligible by automation tools (n =  0) \nOther reasons (n = 0 ) \nStudies excluded (n = 191 ) \nStudies excluded (n = 107 )   \nPre-licensure clinical trial  (n = 40)  \nNo English translation available  (n = 1 ) \nNo vaccine safety outcomes assessed  (n = 5) \nWrong study design, including \ncommentary/editorial , case report, case series \nwithout primary analysis (n = 11 ) \nCoadministration of intervention with other \nvaccines  (n = 4 ) \nWrong intervention (intervention -specific data \nnot included in study)  (n = 20)  \nStudy participants age not limited to 12 months \nto 12 years  (n = 6 ) \nStudies included in review (n =  10)     \nScreening  Studies from databases/registers (n = 334 ) \nEmbase  (n = 200)  \nMEDLINE  (n = 111)  \nCochrane Library  (n = 20)  \nCINAHL  (n = 3 ) \nB.4. Data Extractio n and Outcome Summarization  \nData from studies meeting inclusion criteria were independently extracted by four reviewers using \na standardized Microsoft Excel (2021) form, and differences were reconciled by discussion. Outcome data were extracted as presented in the studies. For the purposes of this review, \nstatistical significance was defined as p ≤ 0.05. The evidence was summarized and  synthesized for \neach outcome domain.  \nC. Summary of Evidence  \nC.1. Summaries of Evidence  \nA review of literature was conducted addressing  safety of  MMRV vaccine (ProQuad  or Priorix -Tetra ). \nThis review focused on the v accine safety  for children aged 12 months to 12 years of age.  Priorix -\nTetra is not licensed for use in the United States, but was included in the review due to a similar \nviral strain composition as the ProQuad formulation and a desire to report on comprehensive \nMMRV safety data .  Additionally, this review focused on safety data related to post- licensure \nstudies, and did not include studies that did not present data on MMRV administration without \nother vaccines coadministered on the same day. Refer to Secti on B3 for full exclusion criteria for \nthis review.   The 10 studies reviewed are listed in Table 2.   In the narrative text below , studies \nperformed in the United States are  presented first, and have a brief summary introduction for each \noutcome discussed ; studies performed outside of the United States are briefly summarized under  \nthe international heading s. \n  \nTable 2  \nCharacteristics of  studies meeting inclusion criteria  \nLead a uthor  \nlast name , \nyear of \npublication  Study design  MMRV  trade \nname  \n(ProQuad  or \nPriorix -\nTetr a) Data \ncollection period Sample \nsize, N  Surveillance \nsystem (if applicable)  Country  \nCocchio, \n2016[5]  Prospective \ncohort  Priorix -Tetra  August 1, \n2013 – July \n31, 2014  10395  Not reported  Italy  \nDeichman, \n2015[6]  Randomized \ncomparative \nstudy  ProQuad  January 12, \n2007 – \nFebruary 13, \n2008 947  Not reported  Germany \nand Italy  \nHaas, 2019 [7] Randomized \ncomparative \nstudy  ProQuad  Pre-2019, \notherwise not defined  405  Not reported  France  \nHambidge, \n2014[8]  Self -controlled \ncase series  ProQuad  2004 – 2010  5667  Vaccine Safety \nDatalink  United \nStates  \nJacobsen, \n2009[9]  Retrospective \ncohort  ProQuad  February \n2006 – June \n2007 62596  Kaiser \nPermanente \nSouthern \nCalifornia \nelectronic data \nsystem  United \nStates  \nKlein, \n2010[10]  Self -controlled \ncase series  ProQuad  2000 – 2008  459461  Vaccine Safety \nDatalink  United \nStates  \nKlein, \n2012[11]  Retrospective \ncohort  ProQuad  2006 -2008 \nfor MMRV  \n2000 – 2008 \nfor MMR + V  154188  Vaccine Safety \nDatalink  United \nStates  \nMacDonald, \n2014[12]  Retrospective \ncohort  Priorix -Tetra  2006 – 2012  277774  Canadian \nInstitute for Health \nInformation \ndatabase  Canada  \nO’Leary, \n2011[13]  Self -controlled \ncase series  ProQuad  2000 – 2009  1.8 million  Vaccine Safety \nDatalink  United \nStates  \nRowhani -\nRahbar, \n2013[14]  Retrospective \ncohort  ProQuad  2001 -2011  840348  Vaccine Safety \nDatalink  United \nStates  \nTable 3  \nSelected outcomes reviewed in studies meeting inclusion criteria  \nLead author last name, \nyear of publication  MMRV trade \nname (ProQuad \nor Priorix -Tetra)  Country  Outcome(s)  summarized  \nCocchio, 2016 [5] Priorix -Tetra  Italy  Febrile seizure, afebrile seizure, fever, \nirritability, parotid swelling, arthralgia,  \nlocal reaction s (pain, swelling, \nredness ) \nDeichman, 2015 [6] ProQuad  Germany and Italy  Febrile seizure,  fever, irritability,  local \nreactions (pain, swelling, redness)  \nHaas, 2019 [7] ProQuad  France  Fever, mumps -like illness  \nHambidge, 2014 [8] ProQuad  United States  Seizure  (not otherwise specified)  \nJacobsen, 2009 [9] ProQuad  United States  Febrile seizure  \nKlein, 2010 [10]  ProQuad  United States  Febr ile seizure  \nKlein, 2012 [11]  ProQuad  United States  Febrile seizure , fever  \nMacDonald, 2014 [12]  Priorix -Tetra  Canada  Seizure (not otherwise specified)  \nO’Leary, 2011 [13]  ProQuad  United States  Immune thrombocytopenic purpura  \nRowhani -Rahbar, 2013 [14]  ProQuad  United States  Seizure  (not otherwise specified ), \nfever  \n \nNeurologic al outcomes  \nFebrile seizure  \n One retrospective cohort (Jacobsen, 2009) and one self- controlled case series within the \nVaccine Safety Datalink (VSD)  (Klein, 2010) suggested an increased risk for febrile seizures \nfollowing MMRV vaccination compared to separately administered MMR and varicella vaccines on \nthe same day  in children aged 12 -60 months and children aged 12 -23 months, respectively.   \nAnother retrospective cohort within VSD  (Klein, 2012) suggested that MMRV and MMR + V were not \nassociated with increased risk of febrile seizures among children aged 4 -6 years old.   \n• Retrospective cohort (Jacobsen , 2009)  of 62596 children aged 12 -60 months who either \nreceived MMRV vaccination (n=31298) or MMR+V vaccination given separately at the same visit \n(n=31298).   The study identified 84 cases of confirmed febrile convulsion; there were 1.41/1000 \n(n=44) confirmed febrile convulsion diagnoses in the MMRV cohort, and 1.28/1000 (n=40) confirmed febrile convulsion diagnoses in the MMR+V cohort.  The analysis suggested  no \nsignificant difference between MMRV and MMR+V in confirmed febril e convulsion in the 30 \ndays following vaccination (RR=1.1 [95% CI, 0.72 -1.69]).  In days 5 -12 following vaccination, the \nstudy identified 32 cases of confirmed febrile convulsion, with 0.7/1000 (n=22) confirmed \nfebrile convulsion diagnoses in the MMRV cohort, and 0.32/1000 (n=10 ) confirmed febrile \nconvulsion diagnoses in the MMR+V cohort; there was a suggested increased risk in the MMRV \ncohort in the 5 -12-day post -vaccination window (RR=2.2 [95% CI, 1.04 -4.65]).  \n• Self-controlled case series (Klein , 2010)  analyzed 459461 healthy children aged 12 -23 months  \nwithin VSD , comparing MMRV vaccine recipients (n=83107) to recipients of MMR + V vaccines \ngiven on the same day (n=376354).  The analysis suggested an increased risk for febrile seizures \nafter MMRV compared to separately administered same -day MMR and V vaccines (RR= 1.98 \n[95% CI, 1.43 -2.73]); the excess risk per 10,000 doses was 4.6 (95% CI, 2.8 -5.9).  \n• Retrospective cohort study  (Klein , 2012)  of 154188 children aged 4 -6 years  within VSD  analyzed \nwhether MMRV (n=86750) or same -day MMR+V (n=67438) affects risk for febrile seizure.  There \nwas one febrile seizure 7 -10 days after MMRV and 0 after MMR+V.  Febrile seizure risk was 1 per \n86750 MMRV doses (95% CI, 1 per 3426441, 1 per 15570), and  0 per 67438 MMR+V doses (95% \nCI, 0, 1 per 18282).  \n \nSeizure (not otherwise specified)  \nA self -controlled case series within VSD  (Hambidge, 2014)  suggested an association of more \npostvaccination seizures in delayed MMRV vaccination (administered between age 12-15 months ) \ncompared to on- time MMRV vaccination (administered between age 16-23 months) .  \nA retrospective cohort within VSD  (Rowhani -Rahbar , 2013) found that the incidence of seizures \nduring the 7 -10 days following immunization with MMRV was significantly greater than that \nfollowing immunization with MMR with or without varicella administered separately on the same \nday.   The study suggested a 2 -fold increase in the risk of seizures in the 7 -10 days following MMRV \nvaccination  compared with MMR administered with or without varicella vaccine in both younger (12 \nto 15 months of age) and older childr en (16 to 23 months of age).    \n• Self-controlled case series within VSD  (Hambidge , 2014) analyzed timely versus delayed early \nchildhood vaccination in a cohort of 5667 children with diagnosis of first seizure between 38 and 730 days of life.  For on -time MMRV vaccination (administered at age 361 – 488 days), the \nIRR for seizure in the 7 -10 day s after vaccination was 4.95 (95% CI, 3.68 -6.66). For delayed \nreceipt of MMRV (administered at age 489 -730 days), the IRR was 9.8 (95% CI, 4.35 -22.06).  The \nvaccine -seizure association was most pronou nced if MMRV vaccine was administered \nbetween 16 and 18 months of age (IRR 11 [95% CI, 4.26 -28.38]).  \n• Retrospective cohort study  within VSD  (Rowhani -Rahbar , 2013)  examined the effect of age on \nthe risk of fever and seizures following immunization with measles- containing vaccines in \nchildren aged 12 to 23 months of age (N =840348). A MMRV vs MMR +/ - V cohort analysis in \nparticipants aged 12 -15 months indicated an in creased risk in seizures among MMRV \nrecipients (IRR 2.0 [95% CI, 1.4 -2.8]), with an excess risk of 4.2 cases per 10000 doses (95% CI, \n1.8-16.3). A MMRV vs MMR +/-  V cohort analysis in participants aged 16 -23 months indicated an \nincreased risk in seizures among MMRV recipients (IRR 2.1 [95% CI, 1.3 -3.3]), with an excess \nrisk of 9 cases per 10000 doses (95% CI, 1.8 -16.3).  The relative risk of seizure during the 7 -10 \ndays following MMRV immunization (MMR with or without varicella administered separately on \nthe same day as the reference) was not statistically different between children 16 to 23 months \nof age and those 12 to 15 months of age.  The attributable risk of seizures during the 7 -10 days \nfollowing MMRV immunization (MMR with or without varicella admi nistered separately on the \nsame day as the reference) was greater among children 16 to 23 months of age than among \nchildren 12 to 15 months of age; however, the difference did not gain statistical significance . \n \nMMRV vaccine safety in international settings  – Neurological outcomes  \n• One prospective cohort from Italy  (Cocchio , 2016) of 10395 healthy fourteen -month old \nchildren eligible for their first vaccination against measles, mumps, rubella, and varicella assessed adverse events relating to two different vaccination strategies: Priorix -Tetra  \nvaccination (n=5265) or separate MMR and varicella vaccination administered on the same day \n(n=5130).  This study repor ted no difference in risk of febrile seizure following MMR + V \ncompared to Priorix -Tetra  [RR 0.80 (95% CI, 0.30 -2.15)] or afeb rile seizure following MMR + \nV compared to Priorix -Tetra  [RR 2.05 (95% CI, 0.18 -22.6)].  \n• One randomized comparative study  (Deichmann, 2015) of 947 healthy German and Italian \nchildren aged ≥12 to <24 months randomly assigned the children to one of three vaccination \narms in a 2:1:1. Group 1 received one MMRV dose and one hexavalent vaccine concomitantly \nat separate injection sites, group 2 received MMRV only, and group 3 received the hexavalent \nvaccine only.  In the MMRV -only group (n=234), no participants were reported to have febrile \nconvulsion within 0 -28 days following vaccination . \n• One retrospective cohort study from Canada  (MacDonald , 2014)  compared the risk of \nseizures after the first dose of Priorix -Tetra  with the risk after same -day administration of \nseparate MMR + V in 277774 children aged 12 to 23 months.  The risk of seizures 7 -10 days \nafter vaccination was twice as high with Priorix -Tetra  as with MMR + V (RR 1.99 [95% CI, \n1.3-3.05]).  The excess absolute risk of seizures was 3.52 seizures per 10000 doses of \nPriorix -Tetra  relative to MMR_V.  In high -risk children (those with a pe rsonal history of febrile \nseizure; seizure disorder; central nervous system injury, infection or neoplasm; \nencephalopathy; or a progressive, evolving or unstable neurologic condition), the risk was not \ndifferentially higher fo r Priorix -Tetra  (RR 1.3 [95% CI, 0.6 -2.79]).  \n \nSystemic reaction  outcomes  \nFever  \nA retrospective cohort within VSD  (Klein, 2012) reported that there was no  apparent  peak in \noutpatient fever visits during days 7 to 10 after MMRV, MMR or varicella vaccines , and that \noutpatient fever visits 7 to  10 days were not significantly higher after MMR + V than after MMR \nalone, although there was a trend in that direction.  \nAnother retrospective cohort study  within VSD  (Rowhani -Rahbar, 2013)  found that the \nincidence of fever during the 7 -10 days following immunization with MMRV was significantly greater \nthan that following immunization with MMR with or without varicella administered separately on \nthe same day.  The study suggested a 1.4-fold increase in the risk of fevers  in the 7 -10 days \nfollowing MMRV vaccination compared with MMR administered with or without varicella vaccine in \nboth younger (12 to 15 months of age) and older children (16 to 23 months of age).   \n• The Klein (2012) r etrospective cohort within VSD reported o utpatient fever visits for MMRV \nrecipients occurred at an adjusted rate of 5.2 per 100 person- years (95% CI, 3.9 -6.8)) in the 7 -\n10-day post -vaccination window, and 5 per 100 person- years (95% CI, 4.5 -5.4) in the 0 -42-day \npost -vaccination window. Outpatient fever visits for MMR+V recipients occurred at an adjusted \nrate of 8.8 per 100 person -years (95% CI, 6.2 -12) in the 7 -10-day post -vaccination window, and \n6.4 per 100 person -years (95% CI, 5.7 -7.2) in the 0 -42-day post -vaccination window. \n• The Rowhani -Rahbar (2013) r etrospective cohort within VSD  reported that a MMRV vs MMR +/ - \nV cohort analysis in participants aged 12 -15 months indicated an increased risk in fever among \nMMRV recipients (IRR 1.4 [95% CI, 1.3 -1.5]), with an excess risk of 8.9 cases per 10000 doses \n(95% CI, 3.2 -15.2); in a cohort of participants age d 16 -23 months the IRR was 1.4 (95% CI, 1.1 -\n1.7).  \n \nMMRV vaccine safety in international studies  – systemic reactions outcomes  \n• Randomized comparative study  (Deichmann , 2015) of 947 healthy German and Italian \nchildren aged ≥12 to <24 months randomly assigned the children to one of three vaccination \narms in a 2:1:1. Group 1 received one MMRV dose and one hexavalent vaccine concomitantly \nat separate injection sites, group 2 recei ved MMRV only, and group 3 received the hexavalent \nvaccine only.  In the MMRV -only group (n=234), 61.1% (n=143) were reported to have a t least \none rectal (or equivalent) temperature ≥38 degrees Celsius  within 0 -28 days following vaccination \n(48 of those study participants were reported to have at least one rectal (or equivalent ) \ntemperature  ≥39.4 degrees Celsius) ; 1.3% (n=3) were reported to have irritability  within 0 -28 \ndays following vaccination; no participants were reported to have mumps/mumps- like illn ess \nwithin 0 -28 days following vaccination.  \n• One prospective cohort from Italy  (Cocchio , 2016) of 10395 healthy fourteen -month old \nchildren eligible for their first vaccination against measles, mumps, rubella, and varicella \nassessed adverse events relating to two different vaccination strategies: Priorix -Tetra  \nvaccination (n=5265) or separate MMR and varicella vaccination administered on the same day \n(n=5130).   The findings suggested a decreased risk of fever ≤ 39.4 degrees Celsius following \nMMR + V compared to Priorix -Tetra  [RR 0.58 (95% CI, 0.54 -0.63)]. This study reported no \ndifference in risk of fever ≥ 39.5 degrees Celsius  following MMR + V compared to Priorix -Tetra  \n[RR 0.80 (95% CI , 0.69 -1.00)] , an increased risk of irritability  following MMR + V compared to \nMMRV*  [RR 1.35 (95% CI, 1.21 -1.51)] , increased risk of parotid swelling following MMR + V \ncompared to  Priorix -Tetra  [RR 1.73 (95% CI, 1.02 -2.92)] , and an increased risk of arthralgia \nfollowing MMR + V compared to Priorix -Tetra  [RR 1.82 (95% CI, 1.17 -2.82)] . \n• Randomized comparative study  (Haas , 2019) of 405 healthy French children aged 12 -18 \nmonths compared intramuscular (IM) and subcutaneous (SC) administration of two doses of MMRV given one month apart.  In the 0 -28 days following the first MMRV dose administered by \nIM route (n=202) or by SC route (n=203 ), vaccine -related pyrexia  was reported in 35.6% (n=72) \nand 39.4% (n=80) of recipients, respectively ; and mumps/mumps -like illness  was reported in  \nthe 0.5% (n=1) and 0% (n=0) of participants, respectively . In the 0 -28 days following the second \nMMRV dose administered by IM route (n=201) or SC route (n=200), vaccine -related pyrexia  \nwas reported in 16.9% (n=34) and 17% (n=34) of participants, respectively ; and \nmumps/mumps -like illness  was reported in the 0.5% (n=1) and 0% (n=0) of participants, \nrespectively . \nLocal reactions outcomes  \nThere were no studies from the United States in this review that assessed local reactions \noutcomes.  \nMMRV vaccine safety in international studies – pain outcome  \n• One prospective cohort from Italy  (Cocchio , 2016) of 10395 healthy fourteen -month old \nchildren eligible for their first vaccination against measles, mumps, rubella, and varicella \nassessed adverse events relating to two different vaccination strategies: Priorix -Tetra  \nvaccination (n=5265) or separate MMR and varicella vaccination administered on the same day (n=5130).   The findings suggested an increased risk of pain following MMR+V compared to \nPriorix -Tetra  [RR 3.33 (95% CI, 2.79 -3.98)].  \n• One randomized comparative study  (Deichmann, 2015) of 947 healthy German and Italian \nchildren aged ≥12 to <24 months randomly assigned the children to one of three vaccination \narms in a 2:1:1. Group 1 received one MMRV dose and one hexavalent vaccine concomitantly \nat separate injection sites, group 2 received MMRV only, and group 3 received the hexavalent \nvaccine only.  In the MMRV -only group (n=234), 14.1% (n=33) were reported to have injection-\nsite pain within 0 -28 days following vaccination. owing vaccination  in groups 1 and 3, \nrespectively . \nMMRV vaccine safety in international studies – swelling  outcome  \n• One prospective cohort from Italy  (Cocchio , 2016) of 10395 healthy fourteen -month old \nchildren eligible for their first vaccination against measles, mumps, rubella, and varicella assessed adverse events relating to two different vaccination strategies: Priorix -Tetra  \nvaccination (n=5265) or separate MMR and varicella vaccination administered on the same day \n(n=5130).  The findings suggested an increased risk of swelling following MMR + V compared \nto Priorix -Tetra  [RR 3.38 (95% CI, 2.45 -4.68)].  \n• One randomized comparative study  (Deichmann, 2015) of 947 healthy German and Italian \nchildren aged ≥12 to <24 months randomly assigned the children to one of three vaccination arms in a 2:1:1. Group 1 received one MMRV dose and one hexavalent vaccine concomitantly at separate injection sites, group 2 received MMRV only, and group 3 received the hexavalent \nvaccine only. In the MMRV -only group (n=234), 2.6% (n=6) were reported to have injection -site \nswelling  within 0 -28 days following vaccination.  \nMMRV vaccine safety in international studies – redness outcome  \n• One prospective cohort from Italy  (Cocchio , 2016) of 10395 healthy fourteen -month old \nchildren eligible for their first vaccination against measles, mumps, rubella, and varicella \nassessed adverse events relating to two different vaccination strategies: Priorix -Tetra  \nvaccination (n=5265) or separate MMR and varicella vaccination administered on the same day \n(n=5130).  The findings suggested an increased risk of redness following MMR + V compared \nto Priorix -Tetra  [RR 4.89 (95% CI, 3.73 -6.42)].  \n• One randomized comparative study  (Deichmann, 2015) of 947 healthy German and Italian \nchildren aged ≥12 to <24 months randomly assigned the children to one of three vaccination \narms in a 2:1:1. Group 1 received one MMRV dose and one hexavalent vaccine concomitantly at separate injection sites, group 2 received MMRV only, and group 3 received the hexavalent \nvaccine only.  In the MMRV -only group (n=234), 10.7% (n=25) were reported to have injection \nsite erythema  within 0 -28 days following vaccination.  \n \nHematologic al outcome  \nImmune thrombocytopenic purpura  (ITP)  \n• A self -controlled case series  (O’Leary, 20 11) with a cohort of 1.8 million children aged 6 \nweeks to 17 years within VSD  identified a total of 197 chart- confirmed ITP cases.  The analysis \nindicated no significant elevated risk of ITP in MMRV recipients aged 12 -19 months within \nthe 1 - to 42 -day post -vaccination window (IRR 2.87 [95% CI, 0.78 -10.56].   \nAppendix  \nTable 3  \nPrimary search strategy of MEDLINE (OVID), Embase (OVID), Cochrane Library CINAHL \n(EBSCOHost),   \nDATABASE  STRATEGY  RUN DATE  RECORD \nCOUNT  \nMedline  \n(OVID)  \n1946-  1. (Measles -Mumps -Rubella -Varicella OR chickenpox measles \nmumps rubella vaccine OR MMRV OR ProQuad).mp   \n2. Exp Safety/ OR exp Treatment Outcome/ OR \"Drug -Related \nSide Effects and Adverse Reactions\"/   \n3. (safety OR (vaccin* ADJ2 safe*) OR treatment outcome* OR \nadverse* OR harm OR harmful OR harms OR side \neffect*).ti,ab,kf. OR ae.fs   \n4. 2 OR 3  \n5. Exp Clinical Study/ OR exp Product Surveillance, Postmarketing/    \n6. (trial* OR observational stud* OR observation stud* OR \nclinical stud* OR surveillance OR reporting system* OR VAERS OR postmarket* OR post -market*).ti,ab,kf,hw.   \n7. 5 OR 6  \n8. 1 AND 4 AND 7  \n9. Exp animals/ NOT exp humans/   \n10. 10 NOT 11  \n 08/1/2025  111 \nEmbase  \n(OVID)  \n1947-  1. chickenpox measles mumps rubella vaccine/   \n2. (Measles -Mumps -Rubella -Varicella OR chickenpox measles \nmumps rubella vaccine OR MMRV OR ProQuad).ti,ab,kf.   \n3. 1 OR 2  \n4. Exp Safety/ OR exp Treatment Outcome/ OR adverse drug reaction/  \n5. (safety OR (vaccin* ADJ2 safe*) OR treatment outcome* OR adverse* OR harm OR harmful OR harms OR side effect*).ti,ab,kf. OR ae.fs   \n6. 4 OR 5  \n7. Exp Clinical Study/ OR exp Postmarketing Surveillance/   \n8. (trial* OR observational stud* OR observation stud* OR clinical stud* OR surveillance OR reporting system* OR VAERS OR postmarket* OR post -market*).ti,ab,kf,hw.   \n9. 7 OR 8  \n10. 3 AND 6 AND 9  \n11. Exp animal/ NOT exp human/   \n12. 10 NOT 11  \n13. limit 12 to \"pubmed/medline\"   08/1/2025  297 \n \n- \nDUPLICATES   \n \n=200 \nUNIQUE \nRECORDS  \nDATABASE  STRATEGY  RUN DATE  RECORD \nCOUNT  \n14. 12 NOT 13   \n15. limit 14 to conference abstract status   \n16. 14 NOT 15  \n17.  \nCochrane \nLibrary  \n #1 (Measles -Mumps -Rubella -Varicella:ti,ab,kw OR “chickenpox \nmeasles mumps rubella vaccine”:ti,ab,kw OR MMRV:ti,ab,kw \nOR ProQuad:ti,ab,kw)   \n#2 [mh Safety] OR [mh \"Treatment Outcome\"]    \n#3 (safety:ti,ab,kw OR (vaccin*:ti,ab,kw NEAR/2 safe*:ti,ab,kw) \nOR (\"treatment\" NEXT outcome*):ti,ab,kw OR adverse*:ti,ab,kw OR harm:ti,ab,kw OR harmful:ti,ab,kw OR \nharms:ti,ab,kw OR (\"side\" NEXT effect*):ti,ab,kw)   \n#4 #2 OR #3  \n#5 [mh ^\"Clinical Study\"] OR [mh ^\"Product Surveillance, \nPostmarketing\"]   \n#6 (trial*:ti,ab,kw OR (\"observational\" NEXT stud*):ti,ab,kw OR \n(\"observation\" NEXT stud*):ti,ab,kw OR (\"clinical\" NEXT stud*):ti,ab,kw OR surveillance:ti,ab,kw OR (\"reporting\" NEXT system*):ti,ab,kw OR VAERS:ti,ab,kw OR postmarket*:ti,ab,kw OR post -market*:t i,ab,kw)   \n#7 #5 OR #6  \n#8 #1 AND #4 AND #7  \n 08/1/2025  54 \n \n- \nDUPLICATES   \n \n=20 \nUNIQUE \nRECORDS  \nCINAHL  \n(EBSCOHost)  S1 (Measles -Mumps -Rubella -Varicella OR “chickenpox measles \nmumps rubella vaccine” OR MMRV OR ProQuad)   \nS2 (MH Safety+) OR (MH \"Treatment Outcomes+\") OR (MH \n\"Adverse Drug Event+\")   \nS3 ((TI safety OR AB safety OR SU safety) OR ((TI vaccin* OR AB \nvaccin* OR SU vaccin*) N2 (TI safe* OR AB safe* OR SU safe*)) OR (TI \"treatment outcome*\" OR AB \"treatment outcome*\" OR SU \"treatment outcome*\") OR (TI adverse* OR AB adverse* OR SU adverse*) OR (TI harm OR AB harm OR SU \nharm) OR (TI harmful OR AB harmful OR SU harmful) OR (TI \nharms OR AB harms OR SU harms) OR (TI \"side effect*\" OR AB \n\"side effect*\" OR SU \"side effect*\"))   \nS4 S2 OR S3   \nS5 (MH \"Clinical Study+\") OR (MH \"Product Surveillance, \nPostmarketing+\")   08/1/2025  5 \n \n- \nDUPLICATES   \n =3 \nUNIQUE RECORDS  \nDATABASE  STRATEGY  RUN DATE  RECORD \nCOUNT  \nS6 ((TI trial* OR AB trial* OR SU trial*) OR (TI \"observational \nstud*\" OR AB \"observational stud*\" OR SU \"observational \nstud*\") OR (TI \"observation stud*\" OR AB \"observation stud*\" OR SU \"observation stud*\") OR (TI \"clinical stud*\" OR AB \"clinical stud*\" OR S U \"clinical stud*\") OR (TI surveillance OR \nAB surveillance OR SU surveillance) OR (TI \"reporting system*\" OR AB \"reporting system*\" OR SU \"reporting system*\") OR (TI VAERS OR AB VAERS OR SU VAERS) OR (TI postmarket* OR AB postmarket* OR SU postmarket*) OR (TI post -market* OR AB \npost -market* OR SU post -market*))   \nS7 S5 OR S6   \nS8 S1 AND S4 AND S7  \nS9 Limiters - Exclude MEDLINE records   \n \n  \nReferences  \n1. Tillieux, S.L., et al., Comparative analysis of the complete nucleotide sequences of \nmeasles, mumps, and rubella strain genomes contained in Pr iorix -Tetra and ProQuad live \nattenuated combined vaccines.  Vaccine, 2009. 27(16): p. 2265 -73. \n2. CDC, Prevention of varicella: recommendations of the Advisory Committee on \nImmunization Practices (ACIP).  MMWR, 2007. 56 : p. No. RR -4. \n3. CDC, Update: recommendations from the Advisory Committee on Immunization Practices \n(ACIP) regarding administration of comibination MMRV vaccine.  MMWR, 2008. 57 : p. 258 --\n60. \n4. Marin, M., et al., Use of combination measles, mumps, rubella, and varicella vaccine: \nrecommendations of the Advisory Committee on Immunization Practices (ACIP).  MMWR \nRecomm Rep, 2010. 59(Rr-3): p. 1 -12. \n5. Cocchio, S., et al., A postmarket safety comparison of 2 vaccination strategies for measles, \nmumps, rubella and varicella in Italy.  Hum Vaccin Immunother, 2016. 12 (3): p. 651 -4. \n6. Deichmann, K.A., et al., Immunogenicity and safety of a combined measles, mumps, \nrubella and varicella live vaccine (ProQuad ®) administered concomitantly with a booster \ndose of a hexavalent vaccine in 12 -23-month- old infants.  Vaccine, 2015. 33 (20): p. 2379 -86. \n7. Haas, H., et al., Immunogenicity and safety of intramuscular versus subcutaneous administration of a combined measles, mumps, rubella, and varicella vaccine to children \n12 to 18 months of age.  Hum Vaccin Immunother, 2019. 15(4): p. 778 -785.  \n8. Hambidge, S.J., et al., Timely versus delayed early childhood vaccination and seizures.  \nPediatrics, 2014. 133 (6): p. e1492 -9. \n9. Jacobsen, S.J., et al., Observational safety study of febrile convulsion following first dose \nMMRV vaccination in a managed care setting.  Vaccine, 2009. 27 (34): p. 4656 -61. \n10. Klein, N.P., et al., Measles -mumps- rubella -varicella combination vaccine and the risk of \nfebrile seizures.  Pediatrics, 2010. 126 (1): p. e1 -8. \n11. Klein, N.P., et al., Measles -containing vaccines and febrile seizures in children age 4 to 6 \nyears.  Pediatrics, 2012. 129 (5): p. 809 -14. \n12. MacDonald, S.E., et al., Risk of febrile seizures after first dose of measles- mumps -rubella-\nvaricella vaccine: a population- based cohort study.  Cmaj, 2014. 186 (11): p. 824 -9. \n13. O'Leary, S.T., et al., The risk of immune thrombocytopenic purpura after vaccination in \nchildren and adolescents.  Pediatrics, 2012. 129 (2): p. 248 -55. \n14. Rowhani -Rahbar, A., et al., Effect of age on the risk of Fever and seizures following \nimmunization with measles -containing vaccines in children.  JAMA Pediatr, 2013. 167 (12): p. \n1111 -7.", "summary": "Rapid Systematic Review of the Safety of MMRV Vaccine   A. Background   The measles -mumps -rubella -varicella (MMRV) vaccine (ProQuad, Merck) was licensed in the  United States in 2005 for use in children 12 months through 12 years of age. While not licensed  for use in the United States, Priorix -Tetra, a MMRV vaccine manufactured by GlaxoSmithKline ,  first received licensing in some European countries in 2006, and in Canada in 2007.  Both  ProQuad and Priorix -Tetra are tetravalent…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-september-18-19-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-09-18-19/MMRV-vaccine-safety-summary-508.pdf", "doc_date": "2025-09-18", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 15}
{"title": "policy recs mmrv briefing 508", "content": "1 \n Briefing Document : Policy Recommendations for  Use of           \nMeasles , Mumps , Rubella, and Varicella (MMRV) Vaccine  in the \nUnited States  \n \nOverall Summary:  \n• Current ACIP/CDC recommendations  for MMRV vaccine use in the U .S. summary  \n(MMWR, May 2010): \no The routinely recommended ages for measles, mumps, rubella and varicella \nvaccination are 12 –15 months for the first dose and 4 –6 years for the second dose.  \n Both the first and second dose can be administered at other ages provided  \nthe minimum age and the interval between doses are respected . \n For children aged 12 months through 12 years, two vaccination options are available to implement the ACIP recommendation : 1) trivalent measles, \nmumps, rubella (MMR)  vaccine and monovalent varicella vaccine \nadministered as two separate injections or 2) combination MMRV vaccine administered as one injection.  MMRV vaccine is licensed for use through 12 \nyears of age.  \no For the first dose of measles, mumps, rubella, and varicella vaccines at age 12 –\n47 months , either MMR vaccine and varicella vaccine or MMRV vaccine may be \nused. Providers who are considering administering MMRV vaccine should discuss the benefits and risks of both vaccination options with the parents or caregivers. Unless the parent or caregiver expresses a preference for MMRV vaccine,  CDC \nrecommends  that  MMR vaccine and varicella vaccine should be administered \nfor the first dose in this age group . \no For the second dose  of measles, mumps, rubella, and varicella vaccines at any age  \nthrough 12 years  (i.e., 15 months –12 years) and for the first dose at age ≥48 months, \nuse of MMRV vaccine generally is preferred over separate injections of its \nequivalent component vaccines (i.e., MMR vaccine and varicella vaccine). \nConsiderations should include provider assessment, patient preference, and the \npotential for adverse events.  \n• The two vaccination options (MMRV vaccine or separate injections of MMR vaccine and \nvaricella vaccine) are considered equivalent in terms of protection against measles, \nmumps, rubella, and varicella . \n• Febrile seizures are a rare event after MMRV vaccination (7 -8.5 per 10,000 vaccinations).  \nCompared with separate administration of MMR vaccine and varicella vaccine at the same \ntime , among children aged 12 -23 months, an estimated 1 additional febrile seizure occurs \nper 2,300 –2,600 children vaccinated with the first dose MMRV vaccine.  \n• MMRV vaccine account s for 15.1%  (range by state 5.1% -31.8%, Q1 : 10.4%, Q3 : 18.3%) of \nfirst dose  measles, mumps, rubella, and varicella vaccination among children 19 -35 \nmonths of age (National Immunization Survey -Child, 2023)  and ~75%  (range by jurisdiction \n46% -96% ) of second dose  vaccination  (data  from 39 jurisdiction I mmunization Information \nSystem s, children age  4-6 years  by Dec 31, 202 4 who received an MMR -containing vaccine , \nCDC, unpublished data ). \n2 \n Methods  \nThis document was developed based on review of the  relevant  literature regarding the measles, \nmumps, rubella, and varicella (MMRV) vaccine licensed in the U .S. (Proquad, Merck &Co., Inc.) for \ngeneral vaccine safety, association with febrile seizures, and immunogenicity; review of the \nliterature regarding the second MMRV vaccine, available internationally (Priorix -Tetra, \nGlaxoSmithKline [GSK] Biologicals) for vac cine efficacy/effectiveness; participation in reviewing of \nthe evidence and discussions during the 2008 -2009 ACIP MMR V Vaccine Safety Work Group; and \nCDC analyses  (unpublished)  on use of MMRV vaccine for the first and second dose vaccination.  \n \nMMRV Vaccine Recommendations and Safety Review :  \n• The currently available MMRV vaccine in the U .S. (Proquad) was licensed  by FDA  in \nSeptember 2005  based on  noninferior immunogenicity  of the antigenic components \ncompared with simultaneous administration of MMR vaccine and varicella vaccine. \nEfficacy of the measles, mumps, rubella, and varicella components of MMRV  vaccine  was \npreviously established in clinical studies with the monovalent vaccines. As FDA licensure \nwas based on immunogenicity (antibody ) comparisons to the individual components (i. e., \nMMR vaccine and varicella vaccine) , studies to evaluate the efficacy of the MMRV \ncombination vaccine were not  performed pre -licensure .  \no At the time of licensure, use of MMRV vaccine was preferred for both the first and second dose of measles, mumps, rubella, and varicella vaccination over separate \ninjections of equivalent component vaccines, consistent with the ACIP \nrecommendation on preferred use of combination vaccines.  \n• In MMRV vaccine pre -licensure clinical trials , two systemic adverse events were reported at \na significantly greater rate 0 -42 days after vaccination in children aged 12 -23 months  who \nreceived a first dose of MMRV vaccine (n = 4,497) compare d with  children who received first \ndoses of MMR vaccine and varicella  vaccine at the same visit  (MMR+ varicella ) (n = 2,038): \nfever ≥102\noF/≥38.9°C  (21.5% vs. 14.9%) and measles -like rash (3.0% vs. 2.1%). Both \nadverse events were reported to occur more frequently 5 –12 days after vaccination and \ntypically resolved spontaneously without sequelae  (MMRV/Proquad Package Insert).   \n• Because of the known association between fever and febrile seizures, CDC (through the Vaccine Safety Datalink  [VSD], which routinely monitors vaccine safety by near real -time \nsurveillance ), and Merck sponsored separate  post -licensure studies  to understand the \nrisk for febrile seizures that might be associated with MMRV vaccination.     \no Preliminary results\n from these two studies were presented to ACIP in February \n2008 and  suggested a 2.3-times higher risk for febrile seizures  among children \naged 12 –23 months during the 5 –12 or 7– 10 days after administration of the first \ndose of MMRV vaccine compared with administration of the first dose  of \nMMR +varicella vaccines at the same visit .  \no ACIP reviewed these preliminary data  on the elevated (but rare, see rates below ) \nrisk for febrile seizure s after MMRV vaccine , as well as other considerations, such \nas vaccine availability  (MMRV had not been distributed in the U .S. since July 2007 \nbecause of manufacturing constraints unrelated to vaccine safety or efficacy and it was not expected to be available again before 2009) . In February 2008 , ACIP issued \nupdated recommendations, changing from a preferential recommendation for MMRV  vaccine , to expressing no preference  for use of MMRV vaccine over separate \n3 \n injections of equivalent component vaccines (i.e., MMR vaccine and varicella \nvaccine) for both the first and second dose.  ACIP also established a W ork Group to \nevaluate post -licensure and other safety data regarding the risk for febrile seizures \nafter MMRV vaccine.  \n \n• The ACIP MMRV Vaccine Safety W ork Group , the first ever ACIP W ork Group  \nestablished specifically to examine the safety of a vaccine, was formed in spring 2008 and examined several lines of evidence during June 2008 -June 2009 .   \no The Work Group  reviewed findings from two post -licensure studies on MMRV \nvaccine and risk for febrile seizures  (unpublished at the time of the discussions); \npre-licensure MMRV vaccine data; literature regarding MMR vaccine and varicella \nvaccine immunogenicity, efficacy, effectiveness, and safety; measles, mumps, \nrubella, and varicella disease burden; the epidemiology of febrile seizures; the \nmedical and psychosoci al importance of febrile seizures; and program \nimplementation considerations. The W ork Group  also reviewed data from focus \ngroups with providers and parents regarding attitudes on multiple injections and \nuse  of MMRV vaccine in the context of an increased risk for febrile seizures after the \nfirst dose  and had consultation s with ethics experts .  \n Summary report from June 2009 ACIP meeting available  here\n (pages 137 -\n165)  \no Post- licensure MMRV vaccine studies reviewed:  \n VSD study  included children aged 12 -23 months : 83,107 received the first \ndose MMRV  vaccine , 376,35 4 received first dose MMR+ varicella vaccines, \nand found that d uring 7 –10 days after vaccination, the unadjusted rate of \nfebrile seizures was 8.5 per 10,000  vaccinations among MMRV vaccine \nrecipients and 4.2  per 10,000  vaccinations among those who received \nMMR +varicella vaccines at the same visit [ adjusted RR: 2.0 (1.4 –2.9); \np=0.0001 ]. \n• Published report: Klein NP, Fireman B, Yih WK, et al. Measles -mumps-\nrubella -varicella combination vaccine and the risk of febrile \nseizures.  Pediatrics . 2010;126(1):e1- e8. doi:10.1542/peds.2010- 0665  \n Merck study  included children aged 12 -60 months (99% aged 12 -23 \nmonths) : 31,298 received first dose MMRV vaccine , 31,298  received first \ndose MMR+ varicella vaccines , and found that 5 -12 days after vaccination, \nthe rate of febrile seizures was 7 per 10,000  vaccinations among MMRV \nvaccine recipients and 3.2 per 10,000  vaccinations among those who \nreceived MMR+ varicella vaccines at the same visit [RR: 2.2 (1.0–4.7); p \n<0.05 ]. \n• Published repo rt: Jacobsen SJ, Ackerson BK, Sy LS, et al. Observational \nsafety study of febrile convulsion following first dose MMRV vaccination in \na managed care setting. Vaccine . 2009;27(34):4656- 4661. \ndoi:10.1016/j.vaccine.2009.05.056  \n Consistent results in both studies: Febrile seizures are a rare event after \nMMRV vaccination (7 -8.5 per 10,000 vaccinations) . The ~twofold \nincreased risk for febrile seizures after MMRV vaccine results in an \n4 \n estimated 1 additional febrile seizure per 2,300 –2,600 children \nvaccinated with the first dose MMRV vaccine compared with those \nreceiving  first dose with MMR+ varicella  vaccines . \n• Of note: the final published results did not differ meaningfully from the unpublished results reviewed by the WG.\n \no Pre-licensure data indicated that the rate of fever after the second dose of MMRV \nvaccine administered to children aged 15 –26 months was lower  than after the first \ndose administered to children the same age as either MMRV vaccine or MMR +varicella vaccines at the same visit.  Among children aged 4 –6 years who \nreceived MMRV vaccine for their second dose, the rate of fever was similar to the rate following a second dose of MMR +varicella  vaccines at the same visit \n[temperature reported as elevated (≥102°F, oral equivalent) or abnormal : MMR V: \n2.5%, MMR+varicella vaccines: 4.1% ].  \n VSD and Merck’s post- licensure studies also examined the risk for febrile \nseizures after the second dose. Results from both studies  suggest ed that \nchildren aged 4 –6 years who receive the second dose of MMRV vaccine  had \nno increased risk for febrile seizures after vaccination compared with \nchildren the same age who receive the second dose of MMR+ varicella  \nvaccines at the same visit.  \n• During 7 –10 days following vaccination, the VSD study identified one \nfebrile seizure among 84,653 children aged 4 –6 years who received \nMMRV vaccine and no febrile seizures among 64,663 children the same age who received MMR +varicella vaccines.  \n• No febrile seizures occurred during the 5 –12 days postvaccination in \neither group in the Merck ’s sponsored study , 25,212 children \nreceived a second dose of MMRV vaccine, and 24,788 received a second dose of MMR +varicella  vaccine s. \no Febrile seizures\n can occur with any condition that causes a fever. Children who \nhave febrile seizures generally have an excellent prognosis. Typically, febrile \nseizures are resolved spontaneously without sequelae . However, first febrile \nseizures often require a medical visit to an emergency department and can be  \ndistressing for parents and caregivers.  \n Maximizing choice based on parent or caregiver and physician preference is \nan important ethical principle. Given the balance of risks and benefits of a first dose of MMRV vaccine compared with a first dose of MMR vaccine and varicella vaccine, and the importance of individual values and preferences in weighing these risks and benefits, decisions should be made by providers and parents or caregivers on a case -by-case basis.  \no In June 2009 , considering the safety and other evidence (e.g., use of MMRV vaccine \nhas the benefit of requiring one less injection than the alternative of MMR+ varicella  \nvaccines , epidemiology of febrile seizures, parent and provider input), ACIP \nrecommended:  \n For the first dose of measles, mumps, rubella and varicella vaccination among children aged 12 -47 months, either MMRV vaccine or separate \ninjections of MMR vaccine and varicella vaccine can be used.  Providers who \n5 \n are considering administering MMRV vaccine as the first dose to young \nchildren should discuss the benefits and risks of both vaccination options \nwith the parents or caregivers.  \n For the first dose at age ≥48 months and the second dose at any age (15 months -12 years) MMRV vaccine is preferred over the component MMR \nvaccine and varicella vaccine.  \no At the time of the publication of the recommendations in the MMWR\n, CDC provided \nguidance regarding implementation of the recommendation for the first dose among young children that unless the parent or caregiver expresses a \npreference for the MMRV vaccine, CDC recommends that MMR vaccine and varicella vaccine should be administered for the first dose among children \naged 12–47 months.  \n• Safety data post- licensure has continued to be closely and regularly monitored. A summary \nof reports received to the Vaccine Adverse Event Reporting System (VAERS) after \nadministration of MMRV vaccine in the U .S. during 2006- 2020 was recently published .  \no Approximately 35.5 million MMRV vaccine doses were distributed; 13 ,325 reports \nwere received (37.6  reports /100 ,000 doses distributed) with 3.3% classified as \nserious (1.3  reports /100 ,000 doses distributed). The most common adverse health \nevents after MMRV vaccine were injection site reactions (27%), rash (20%), and \nfever (14%). No new or unexpected adverse event  was disproportionally \nreported, no new or unexpected safety findings were detected for MMRV vaccine \ngiven as recommended, reinforcing the favorable safety profile of the vaccine.  \n \nImmunogenicity and Effectiveness of MMRV  Vaccine :   \n• Immunogenicity  after the first dose of MMRV  vaccine  vs. MMR+ varicella vaccines in \nchildren aged 12 to 23 months was assessed in 4 randomized clinical trials  (5446 received \nMMRV, 2038 received MMR +varicella  concomitantly at separate injection sites). Children \nenrolled  in these trials had no history  of disease , no known recent exposure, and no \nvaccination history for varicella, measles, mumps, and rubella.  The end points assessed \nwere response rates and geometric mean titers (GMTs).  \no Response rates and GMTs were similar and met the pre -established criteria for non-\ninferiority (lower bound of the 95% CI for the difference in measles, mumps, and \nrubella seroconversion rates > -5.0%, lower bound of the 95% CI for the difference in \nvaricella seroprotection rates was either > -15% [one study] or > -10.0% [three \nstudies])  (Table). \no Work Group assessment during the 2008 -2009 deliberations: given the non -\ninferior immunogenicity, effectiveness was assumed to be equal.   \n \n \n   \n6 \n Table . Summary of c ombined immunogenicity results 6 weeks after  administration of a s ingle \ndose of ProQuad ( varicella virus potency ≥3.97 log10 PFU) or M -M-R II and VARIVAX  \n \n \n          *Combined numbers from 4 trials  with ProQuad with the varicella zoster potency similar to that in the  \n             licensed product ; children aged 12 to 23 months  \n           † The mumps antibody response was assessed by a vaccine -strain ELISA in  2 studies (serostatus was based  \n             on the OD cutoff)  and by a wild- type ELISA in 2 studies . \n           n = Number of per- protocol subjects with evaluable serology.  \n           CI = Confidence interval.  \n           GMT = Geometric mean titer.  \n           ELISA = Enzyme -linked immunosorbent assay.  \n           PFU = Plaque -forming units.  \n           OD = Optical density .    \n \n• No specific post- licensure vaccine effectiveness (VE) estimates are available for the MMRV \nvaccine used in the U .S.  \no MMRV vaccine was licensed in the US in September 2005 and in July 2007 became \ntemporarily unavailable due to manufacturing constraints unrelated to efficacy or \nsafety. MMRV vaccine became available again in the U .S. in 201 2; however,  with \nmeasles and rubella being eliminated in the U .S., mumps at low levels (and \noutbreaks occurring  primarily  in young adults), and the number of cases of varicella \ndeclining 90% by 2010, there were not enough cases of disease or outbreaks in \nchildren to assess vaccine effectiveness in the U .S.   \no Vaccinated persons continue to have very low rates of disease for measles, \nmumps, rubella and varicella in the U.S , including in ages where MMRV is used  \n(data provided in references) . There have been  no reports to CDC indicating \nconcern for lower MMRV vaccine effectiveness compared to use of the separate \ncomponent vaccines, consistent with the  immunogenicity results seen in the  \nclinical trials . \n \n \n \n\n7 \n MMRV vaccine in international settings  \n• The second MMRV vaccine available globally (Priorix -Tetra ) was also licensed based on \nnon- inferior immunogenicity . Note there are important differences in the varicella- zoster \nvirus (VZV) antigen content between Priorix -Tetra and Proquad  (less VZV antigen in Pr iorix-\nTetra) . \no Post- licensure, a randomized, controlled trial  was conducted in 10 European \ncountries that reported on efficacy  against varicella \n 2,279 c hildren aged 12 -22 months  received 2 doses of MMRV  vaccine, 42 \ndays apart ; mean follow -up 36 months .  \n Two  dose MMRV vaccine efficacy against all varicella: 94.9% (92 .4–96.6); \nagainst moderate to severe varicella : 99.5% (97 .5–99.9). \n• Prymula R, Bergsaker MR, Esposito S, et al. Protection against varicella \nwith two doses of combined measles -mumps -rubella -varicella vaccine \nversus one dose of monovalent varicella vaccine: a multicentre, observer-\nblind, randomised, controlled trial - PubMed . Lancet. \n2014;383(9925):1313 -1324.  \n A continuation of th e study above  a median follow -up of 9 .8 years  reported  \n• Two dose MMRV vaccine efficacy against all varicella: 95. 4% (94 .0–\n96.4); against moderate or severe varicella : 99.1% (97 .9–99.6). \no Povey M, Henry O, Bergsaker MR et al. Protection against \nvaricella with two doses of combined measles -mumps -rubella -\nvaricella vaccine or one dose of monovalent varicella vaccine: 10 -\nyear follow -up of a phase 3 multicentre, observer- blind, \nrandomised, controlled trial . L ancet Infect Dis  2019;19: 287– 97. \n \n \nReferences :  \n• CDC/ACIP Recommendations for MMRV use:  \no Current Recommendations: Use of Combination Measles, Mumps, Rubella, and \nVaricella Vaccine Recommendations of the Advisory Committee on Immunization \nPractices; Published May 7, 2010. https://www.cdc.gov/mmwr/pdf/rr/rr5903.pdf   \no Webpage with all MMRV recommendations: https://www.cdc.gov/acip -\nrecs/hcp/vaccine -specific/mmrv.html   \no Summary from June 2009 ACIP meeting where Evidence to Recommendation framework from the MMRV Vaccine Work Group were presented and discussed: \nAdvisory Committee on Immunization Practices (ACIP) summary report : June 24 -\n26, 2009, Atlanta, Georgia   (pages 137 -1 65) \n• The published reports of the two post-licensure studies on MMRV vaccine and febri le \nseizure among children 12 -23 months of age examined by ACIP in 2008 -2009  \no Klein NP, Fireman B, Yih WK, et al. Measles -mumps -rubella -varicella combination \nvaccine and the risk of febrile seizures.  Pediatrics . 2010;126(1):e1 -e8. \ndoi:10.1542/peds.2010- 0665 \n8 \n o Jacobsen SJ, Ackerson BK, Sy LS, et al. Observational safety study of febrile \nconvulsion following first dose MMRV vaccination in a managed care \nsetting.  Vaccine. 2009;27(34):4656 -4661. doi:10.1016/j.vaccine.2009.05.056  \n• Study that examin ed MMRV vaccine and febrile seizures in children 4-6 years of age  \no Klein NP,  Lewis E, Baxter R, et al .  Measles- containing vaccines and febrile seizures \nin children age 4 to 6 years - PubMed . P ediatrics . 2012;129(5):809 -14. \n• MMRV  (Proquad, Merck)  package insert ( Package Insert - Frozen Formulation - ProQuad ) \no Merck added febrile seizures to the PI in Feb 2008 in the section of post- marketing \nexperience (under Nervous system disorders), Approved Products > February 27, \n2008 Approval Letter - ProQuad  \no Addition of “ additional safety data after a first or second dose of ProQuad® ” \napproved in October 29, 2009, Approved Products > October 29, 2009 Approval \nLetter - ProQuad  \n• MMRV (Priorix -Tetra, GSK) randomized clinical trials  \no Prymula R, Bergsaker MR, Esposito S, et al. Protection against varicella with two \ndoses of combined measles -mumps -rubella -varicella vaccine versus one dose of \nmonovalent varicella vaccine: a multicentre, observer -blind, randomised, \ncontrolled trial - PubMed . L ancet. 2014; 383(9925):1313 -1324.  \no Povey M, Henry O, Bergsaker MR et al. Protection against varicella with two doses of \ncombined measles -mumps -rubella -varicella vaccine or one dose of monovalent \nvaricella vaccine: 10 -year follow -up of a phase 3 multicentre, observer- blind, \nrandomised, controlled trial . L ancet Infect Dis  2019;19: 287– 97. \n• Current /recent epidemiology of measles, mumps, rubella, and varicella (including very low \nrates among vaccinated individuals): Note for diseases eliminated in the US (measles and \nrubella), recent U.S. studies to examine vaccine effectiveness are not possible . \no Measles : Measles Cases and Outbreaks : CDC Website: \nhttps://www.cdc.gov/measles/data -research/index.html   \no Mumps: Tappe J , et al. Characteristics of reported mumps cases in the United \nStats: 2018 -2023. Vaccine 2024;42(25):  \no Rubella : Rubella in the United States: https://www.cdc.gov/rubella/vaccine -\nimpact/index.html    \no Varicella : Shap iro E and Marin M. The effectiveness of varicella vaccine: 25 years of \npost -licensure experience in the United States. The Journal of Infectious Diseases  \n2022: 226 (4): S425 –S430 ; Marin M, Leung J, Anderson TC, Lopez A. Monitoring \nVaricella Vaccine Impact on Varicella Incidence in the United States: Surveillance \nChallenges and Changing Epidemiology, 1995 –2019 . The Journal of Infectious \nDiseases 2022: 226 (4): S 392 -399.", "summary": "1   Briefing Document : Policy Recommendations for  Use of            Measles , Mumps , Rubella, and Varicella (MMRV) Vaccine  in the  United States     Overall Summary:   • Current ACIP/CDC recommendations  for MMRV vaccine use in the U .S. summary   (MMWR, May 2010):  o The routinely recommended ages for measles, mumps, rubella and varicella  vaccination are 12 –15 months for the first dose and 4 –6 years for the second dose.    Both the first and second dose can be administered at other…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-september-18-19-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-09-18-19/policy-recs-mmrv-briefing-508.pdf", "doc_date": "2025-09-18", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 8}
{"title": "02 srinivasan mmrv 508", "content": "Background on Measles, Mumps, Rubella, and Varicella \n(MMRV) Vaccine \nArjun Srinivasan, MD, MS, MBA \nActing Chief Medical Officer \nNational Center for Immunization and Respiratory Di seases \nACIP Meeting \nSeptember 18, 2025 National Center for Immunization & Respiratory Dise ases \nDuring the last major rubella epidemic in the U.S. (1964-1965), in 1 year: \n–11,000 pregnant women lost their babies \n–2,100 newborns died \n–20,000 born with congenital rubella syndrome, causing deaf ness, heart defects \nand developmental delay Measles, mumps, rubella, and varicella caused signi ficant \ndisease burden pre-vaccine in the United States \n2\nBefore the introduction of measles vaccine (1963), each year an estimated: \n–48,000 hospitalizations \n–400-500 deaths \nEach year in the early 1990s (before varicella vaccine): \n–10,500-13,500 hospitalizations \n–100-150 deaths \nMumps was the leading cause of viral encephalitis and sud den onset deafness \nThe introduction of monovalent measles, mumps, rube lla vaccines (1963-1969), followed by \ntrivalent MMR (1971), then monovalent varicella (19 95) and the quadrivalent MMRV (2005) \nvaccines, coupled with attaining and maintaining hi gh coverage rates (>90%) in the United States \n(U.S.) led to: Dramatic reductions in measles, mumps, rubella, and  \nvaricella in the United States after introduction o f vaccines \nManual for the Surveillance of Vaccine-Preventable Diseases for Public Health | Manual for the Surveil lance of Vaccine-Preventable Diseases | CDC 3–Elimination of endemic measles in 2000 \n–Elimination of endemic rubella in 2004 \n–99% decline in mumps cases by early 2000 \n–97% decline in varicella incidence by 2019 \n\nTwo options for measles, mumps, rubella, and varice lla vaccination: MMRV vaccine or \nMMR vaccine + varicella vaccine \n–Recommended as two doses: routine ages - 1st dose: 12-15 months; 2 nd dose: 4-6 years \nThe MMRV vaccine available in the U.S. (ProQuad, Me rck & Co, Inc) was licensed by FDA \nin September 2005 based on noninferior immunogenicity of the antigenic components \ncompared with simultaneous administration of MMR va ccine and varicella vaccine \n–Efficacy of the measles, mumps, rubella, and varicella compo nents of MMRV vaccine was \npreviously established in clinical studies with the monovalent vaccines \n–Burden of disease for these diseases too low to perform efficacy clinical trials in the U.S. MMRV vaccine in the United States \n4\nImmunogenicity after the first dose of MMRV vaccine vs. MMR + varicella vaccines in \nchildren aged 12 to 23 months was assessed in 4 randomized clinical trials \n–5446 received MMRV, 2038 received MMR + varicella v accines at separate injection sites \n–End points assessed (seroconversion rates and geome tric mean titers) were similar and met the pre-\nestablished criteria for noninferiority 1\nImmunogenicity after the second dose of MMRV vaccine vs. MMR vaccine (+/- varicella \nvaccine) in children aged 4-6 years was assessed in  1 randomized clinical trial \n–399 received MMRV, 205 received MMR + placebo, 195 received MMR + varicella vaccine; also met \npre-established criteria for noninferiority \n2008-2009 ACIP Work Group assessment: given the non inferior immunogenicity, \neffectiveness was assumed to be equal Clinical trials for MMRV vaccine \n1Lower bound of the 95% CI for the difference in mea sles, mumps, and rubella seroconversion rates >-5.0% , lower bound of the 95% CI for the \ndifference in varicella seroprotection rates was eit her >-15% [one study] or >-10.0% [three studies] 5\nTimeline of recommendations for MMRV vaccine use in  \nthe United States \n6September 2005 \nMMRV vaccine licensed for children   \naged 12 months–12 years \nUse of MMRV vaccine preferred over separate administration of MMR and \nvaricella vaccines February 2008 \nVaccine safety finding from post-\nlicensure monitoring: increased risk \nof febrile seizures after first dose of \nMMRV vaccine June 2009 \nUpdated recommendations \n(next slide) \nACIP issued interim recommendation: removed \npreference for MMRV use vs. MMR and varicella \nvaccines for both dose 1 and dose 2 1\n1At the time, MMRV vaccine had not been distributed in the U.S. since July 2007 because of manufacturin g constraints unrelated to safety or efficacy: Notice to \nReaders: Update on Supply of Vaccines Containing Va ricella-Zoster Virus .  MMRV vaccine became available again in the U.S. in 2012. \nUse of Combination Measles, Mumps, Rubella, and Var icella Vaccine, MMWR 2010 \nUpdated ACIP recommendations for MMRV vaccine use i n \nthe United States (current recommendations) \nFor the first dose of measles, mumps, rubella, and varicella \nvaccination at age 12–47 months, either MMR vaccine and \nvaricella vaccine or MMRV vaccine may be used. Providers who \nare considering administering the MMRV vaccine shou ld discuss \nthe benefits and risks of both vaccination options with the \nparents or caregivers. \n–CDC provided implementation guidance: unless the pa rent or caregiver \nexpresses a preference for the MMRV vaccine, CDC re commends that \nMMR vaccine and varicella vaccine be administered f or the first dose in \nthis age group. \nFor the first dose at age ≥48 months and for the second dose at \nany age (15 months–12 years), MMRV is generally preferred  \nover separate injections of MMR vaccine and varicel la vaccine \n7\n Use of Combination Measles, Mumps, Rubella, and Var icella Vaccine, MMWR 2010 \nNo post-licensure vaccine effectiveness estimates a re available for the MMRV vaccine \nused in the U.S. \n–With measles and rubella being eliminated in the U. S., mumps and varicella at very low levels, \nthere were not enough cases of disease or outbreaks in children to assess vaccine \neffectiveness in the U.S.  \n–Those vaccinated with MMRV or MMR and varicella vacc ines continue to have very low \nrates of disease for measles, mumps, rubella, and v aricella in the U.S. \n–There have been no reports to CDC indicating concern for lower MMRV vaccine ef fectiveness \ncompared to use of the separate component vaccines,  consistent with the immunogenicity \nresults seen in the clinical trials Post-licensure effectiveness \n8\nMMRV vaccine accounts for 15% of first dose 1measles, mumps, rubella, and varicella \nvaccination among children aged 19-35 months and 75% of second dose 2vaccination \namong children aged 4-6 years \n–First dose range by state: 5.1%-31.8% \n–Second dose range by jurisdiction: 46%-96% MMRV vaccine utilization \n1Data from National Immunization Survey-Child, 2023 \n2Data from 39 jurisdictions’ Immunization Informatio n Systems (IIS), children age 4-6 years by Dec 31, 2024 who received an MMR-\ncontaining vaccine 9\nMMRV vaccine is one of the two options for vaccination of U.S. children for protection \nagainst measles, mumps, rubella, and varicella \nThe two vaccination options (MMRV vaccine or separa te injections of MMR vaccine and \nvaricella vaccine) are considered equivalent in terms of protection against disease \nDue to the current recommendations, most MMRV vacci ne use in the U.S. is among children \nage 4–6 years (for the second dose of MMR and varic ella vaccination) \nVaccination for measles, mumps, rubella, and varice lla has led to at least 97% reduction in \nall four diseases compared with the pre-vaccine eraSummary \n10\nFor more information, contact CDC 1-800-CDC-INFO (2 32-4636) TTY: 1-888-232-6348 \nwww.cdc.gov The findings and conclusions in this report are tho se of the authors and do not \nnecessarily represent the official position of the Centers for Disease Control and \nPrevention. \n•Bloch AB, Orenstein WA, Stetler HC, et al. Pediatri cs 1985;76:524-32. Health impact of measles \nvaccination in the United States \n•CDC. MMWR 2005;54:279–82. Elimination of rubella and congenital rubella syndr ome—United States, \n1969–2004 \n•Marin, et al., JID, 2022, Monitoring Varicella Vaccine Impact on Varicella In cidence in the United States: \nSurveillance Challenges and Changing Epidemiology, 1995–2019 \n•Marin, et al., JID, 2022, Decline in Severe Varicella Disease During the Unit ed States Varicella Vaccination \nProgram: Hospitalizations and Deaths, 1990–2019 \n•National Communicable Disease Center. Rubella surveillance. Bethesda, MD: US Department of Health, \nEducation, and Welfare; 1969. \n•Shapiro, et al., JID, 2022, The Effectiveness of Varicella Vaccine: 25 Years of  Postlicensure Experience in the \nUnited States \n•Witte JJ, Karchmer AW. Public Health Rep, 1968 Feb;8 3(2):5-100. Surveillance of mumps in the United \nStates as background for use of vaccine References: Pre-vaccine burden of measles, mumps, rubella, and varicella \n•Measles : Measles Cases and Outbreaks: CDC Website: https://www.cdc.gov/measles/data-\nresearch/index.html \n•Mumps : Tappe J, et al. Vaccine 2024;42(25): Characteristics of reported mumps cases in the Unit ed Stats: \n2018-2023. \n•Rubella : Rubella in the United States: https://www.cdc.gov/rubella/vaccine-impact/index.ht ml \n•Varicella : Shapiro E and Marin M. The effectiveness of varicella  vaccine: 25 years of post-licensure experience \nin the United States. The Journal of Infectious Diseases 2022: 226 (4): S425–S430 ; Marin M, Leung J, Anderson \nTC, Lopez A. Monitoring Varicella Vaccine Impact on Varicella Incidence in the United States: Surveilla nce \nChallenges and Changing Epidemiology, 1995–2019. The Journal of Infectious Diseases 2022: 226 (4): S392-\n399 .References: Current/recent epidemiology for measles , \nmumps, rubella, and varicella", "summary": "Background on Measles, Mumps, Rubella, and Varicella  (MMRV) Vaccine  Arjun Srinivasan, MD, MS, MBA  Acting Chief Medical Officer  National Center for Immunization and Respiratory Di seases  ACIP Meeting  September 18, 2025 National Center for Immunization & Respiratory Dise ases  During the last major rubella epidemic in the U.S. (1964-1965), in 1 year:  –11,000 pregnant women lost their babies  –2,100 newborns died  –20,000 born with congenital rubella syndrome, causing deaf ness, heart…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-september-18-19-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-09-18-19/02-srinivasan-mmrv-508.pdf", "doc_date": "2025-09-18", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 13}
{"title": "03 su mmrv 508", "content": "Febrile Seizures following Measles, Mumps, Rubella, \nand Varicella (MMRV) vaccine\nJohn Su\nActing Director\nImmunization Safety Office\nCenters for Disease Control and Prevention\nSeptember 18, 2025\nSeptember 2025:  Request to CDC from ACIP Chair\nPresentation on febrile seizures post administration of MMRV vs. \nsimultaneous administration of separate MMR and Varicella vaccines, by \ntwo different age groups, 1 –2 and 4– 6-year -olds. Please use data both from \nrandomized trials and from the Vaccine Safety Datalink (VSD), presented \nfrom the VSD project.\n2\nTimeline of recommendations for MMRV vaccine use in \nthe United States\n3September 2005 : \n MMRV vaccine licensed in \nthe U. S. in children 12 \nmonths –12 years of age\nUse of MMRV vaccine \npreferred over separate \nadministration of MMR and \nvaricella vaccinesFebruary 2008 :  \nVaccine safety finding \nfrom post -licensure \nmonitoring: increased risk \nof febrile seizures after \nfirst doseJune 2009 \nUpdated \nrecommendations \nACIP issued interim recommendation: removed \npreference for MMRV use vs. MMR and varicella \nvaccines for both dose 1 and dose 2 \nPresentation of preliminary safety findings to ACIP \nFebruary 2008 to June 2009 that led to revised MMRV recommendations in June 2009\n•Multiple presentations to ACIP from Vaccine Safety Datalink and Merck\n•Evidence review and synthesis of data to ACIP: MMRV ACIP Working Group \nassessed multiple sources of data\n-Review of two post -licensure studies\n•Merck -sponsored study\n•Vaccine Safety Datalink study\n-Review of literature and other data sources (e.g., parent/provider focus groups data) \n-Consultation with experts\n-MMRV Vaccine Safety Working Group (WG) discussions\n-WG member surveys\n•October 2008 and June 2009\nUse of Combination Measles, Mumps, Rubella, and Varicella Vaccine 4\nACIP Updated Recommendations:  June 2009\n•For the first dose of measles, mumps, rubella, and \nvaricella vaccination at age 12 –47 months, either MMR \nvaccine and varicella vaccine or MMRV vaccine may be used. Providers who are considering administering the MMRV vaccine should discuss the benefits and risks of \nboth vaccination options with the parents or caregivers. \n-CDC implementation guidance: unless the parent or caregiver \nexpresses a preference for the MMRV vaccine, CDC recommends that MMR vaccine and varicella vaccine be \nadministered for the first dose in this age group.\n•For the first dose at age ≥48 months and for the second \ndose at any age (15 months –12 years), MMRV is \ngenerally preferred over separate injections of MMR \nvaccine and varicella vaccine\n5\nMarin, M, et al. Use of Combination Measles, Mumps, Rubella, and Varicella Vaccine: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR May 7, 2010/59(RR03);1 -12\nBackground:  MMRV vaccine\n•Combination vaccine*\n-Decreases the number of injections\n-Increases vaccine compliance\n-Increases vaccine coverage rates\n•MMRV licensed for children 12 months through 12 years of age\n-Routinely recommended ages:\n•First dose: age 12 through 15 months\n•Second dose: age 4 through 6 years\n-In the United States, MMRV vaccine licensed is ProQuad  (Merck & Co, Inc)\n* https://www.cdc.gov/vaccines/hcp/imz -best -practices/timing -spacing -immunobiologics.html  \n6\nBackground:  Febrile seizures\n•By 5 years of age, 2 -4% of children have had ≥ 1 febrile seizure1 \n•Occurs primarily 6 months – 5 years of age, peak age is 14 -18 months\n•Typically of short (<15 min) duration1,2; majority resolve without sequelae\n•Observed during early childhood infections and diseases1, 2\n-Middle ear infections, viral upper respiratory tract infections, roseola\n-Can be associated with any condition that results in fever\n•Observed following a fever associated with vaccination1,2\n-DTaP , pneumococcal conjugate, MMR\n•Family history of febrile seizures increases the risk of febrile seizures3\n1 Marin, M, et al. Use of Combination Measles, Mumps, Rubella, and Varicella Vaccine: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR May 7, 2010/59(RR03);1 -12\n2https://www.cdc.gov/vaccine -safety/about/febrile -seizures.html  \n3 Sawires R, Buttery J, Fahey M. A Review of Febrile Seizures: Recent Advances in Understanding of Febrile Seizure Pathophysiology and Commonly Implicated Viral Triggers. Front Pediatr . 2022 Jan 13;9:801321. 7\nBackground: Pre -licensure MMRV studies\n•MMRV prelicensure studies conducted among children aged 12 to 23 months\n-Fever  and measles- like rash  were reported at significantly greater rate among children \nreceiving the first dose of MMRV vaccine than children receiving first doses of MMR \nvaccine and varicella vaccine (at the same visit)\n•Fever (reported as abnormal or elevated ≥102oF [≥39oC])\n–21.5% of MMRV vaccine recipients compared with 14.9% of separate MMR vaccine and \nvaricella vaccine recipients (risk difference [RD]: 6.6%; 95% confidence interval [CI] = 4.6 -8.5)\n•Measles -like rash:\n–3.0% of MMRV vaccine recipients compared with 2.1% of separate MMR vaccine and \nvaricella vaccine recipients (RD: 1.0%; 95% CI = 0.1 -1.8)\n•In light of these findings, CDC and Merck initiated separate post- licensure \nstudies to evaluate if an increased risk for febrile seizures might be associated \nwith the first dose of MMRV vaccine\n8Marin, M, et al. Use of Combination Measles, Mumps, Rubella, and Varicella Vaccine: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR May 7, 2010/59(RR03);1 -12\nMerck ProQuad  package insert, 2024\nFebrile seizures following first dose of MMRV\n9\nSummary results from VSD and Merck -sponsored studies for chart \nconfirmed febrile seizures after first dose of MMRV vs. MMR and varicella (MMR+V) vaccines  \n*Klein NP, et al. Vaccine Safety Datalink. Measles -mumps- rubella -varicella combination vaccine and the risk of febrile seizures.  Pediatrics. 2010 Jul;126(1):e1 -8\n†Jacobsen SJ et al. Observational safety study of febrile convulsion following first dose MMRV vaccination in a managed care s etting. Vaccine. 2009 Jul 23;27(34):4656 -61. \n§ Significant p <0.05\nRR = relative risk; AR= attributable risk; CI: confidence interval10Post-\nvaccination \nIntervalVSD study*\nAll aged 12 -23 monthsMerck -sponsored study† \n99% aged 12 -23 months\nMMRV: N= 83,107 \nMMR+V: N= 376,354 MMRV: N=31,298 \nMMR+V: N=31,298\nWeeks 1 -2 7–10 days\nRR: 2.0 (95% CI: 1.4, 2.9)§\nAR: 4.3 per 10,000 \n(95% CI: 2.6, 5.6)5–12 days\nRR: 2.2 (95% CI: 1.0, 4.7)§\nAR: 3.8 per 10,000 (95% CI: 0.3, 7.4)  \nWeeks 1 -4\n0-30 days\nRR: 1.4 (95% CI: 1.1, 2.0)§\nAR: 4.7 per 10,000 (95% CI: 0.7, 7.6)0-30 days\nRR: 1.1 (95% CI: 0.7, 1.7)\nAR: 1.3 per 10,000 \n(95% CI: -4.5, 7.0)\nPost -vaccination outpatient fever visits among 12 -23-\nmonth -olds according to vaccine received by vaccine \ntype, VSD, 2000 –2008\n11\nVaccine Days RR P-value\nMMRV*\n(N=83,107)7-10 6.1 0.001\nMMR + V†\n(N=376,354)7-10 4.4 0.001\nMMR†\n(N=145,302)7-10 4.3 0.001\nVaricella†\n(N=107,744)No temporal clustering of fever visits after varicella vaccination alone.Temporal Scan\n* Vaccinated between January 2006 and October 2008; † Vaccinated between January 2000- October 2008\nKlein NP, et al. Vaccine Safety Datalink. Measles -mumps -rubella -varicella combination vaccine and the risk of febrile seizures. Pediatrics. 2010 Jul;126(1):e1- 8\nPost -vaccination febrile seizures among 12- 23-month -\nolds by vaccine type, VSD, 2000 -2008\n12\nTemporal Scan\n* Vaccinated between January 2006 and October 2008; † V accinated between January 2000 -October 2008\nKlein NP, et al. Vaccine Safety Datalink. Measles -mumps- rubella -varicella combination vaccine and the risk of febrile seizures. Pediatrics. 2010 Jul;126(1):e1 -8Vaccine Days RR P-value\nMMRV*\n(N=83,107)8-10 7.6 0.001\nMMR + V†\n(N=376,354)7-10 4.0 0.001\nMMR†\n(N=145,302)7-11 3.7 0.001\nV aricella†\n(N=107,744)No seizure peak observable;  no significant temp oral clustering\nU.S. post -licensure experience:  Febrile seizures after \nMMR or varicella vaccination\n•MMR vaccine: Study of ~137,000 children aged <7 years vaccinated with \nMMR identified an increased risk for febrile seizures during 8 –14 days after \nvaccination, compared with unvaccinated children1\n-RR 2.83 (95% CI: 1.44, 5.55)\n-~1 additional febrile seizure per 3,000 –4,000 children vaccinated\n•Varicella vaccine: Study of ~35,000 children aged 12– 23 months vaccinated \nwith varicella vaccine identified no increased risk for febrile seizures during \n0–30 days after vaccination, after controlling for co- administration of MMR \nvaccine2\n1. Barlow WE, Davis RL, et al. The risk of seizures after receipt of whole- cell pertussis or measles, mumps, and rubella vaccine. N  Engl J Med. 2001 Aug 30;345(9):656 -61.\n2. Black S; Shinefield  H, et al. Postmarketing  evaluation of the safety and effectiveness of varicella vaccine. The Pediatric Infectious Disease Journal 18(12):p 1041 -1046, D ecember \n1999.\n13\nRisk of febrile seizure after MMRV vaccines: \nA systematic review and meta -analysis\n•Included some studies that had subjects as young as 9 months of age\n•Clinical trial review and analysis (31 published or unpublished studies involving \nabout 40,000 subjects)\n-No evidence of significant differences in incidence of febrile seizure or vaccine -related \nfebrile seizure between MMRV and MMR +/ - V after any doses, in the risk windows of 0 -28, \n0-42, 0- 56, and 7- 10 days\n-Receipt of concomitant MMRV and other pediatric vaccines was not a significant predictor \nof febrile seizure\n•Post -marketing review and analysis\n-Included data from 8 post -marketing studies, involving more than 3,200,000 children*\n-Approximately 2 -fold increase in risk of seizure or febrile seizure during 7 -10 days or 5- 12 \ndays after MMRV in children aged 10-24 months\n* One study included children ages 4 -6 years who received second dose MMRV:  Study included both ProQuad  (available in US) and Priorix -Tetra study (available internationally)\nMa SJ, Xiong YQ, Jiang LN, Chen Q. Risk of febrile seizure after measles -mumps -rubella -varicella vaccine: A systematic review an d meta -analysis. Vaccine . 2015;33(31):3636 -3649. \ndoi:10.1016/j.vaccine.2015.06.009 14\nCochrane review: MMRV vs MMR + V in children\n•Febrile seizure review\n-Risk of febrile seizures after MMRV vaccination compared to MMR+V vaccination\n•Includes evidence from five cohort studies*\n•Overall estimates:\n–Within 42 days after vaccination: RR 1.31 (95% CI: 1.19 to 1.45) \n–Within 7 to 10 days after vaccination: RR 1.98 (95% CI: 1.69 to 2.33) \n-Risk of febrile seizure after MMRV studies (grouped by brand) compared to MMR+V \nvaccination\n•Priorix -Tetra study:\n–Within 0 to 42 days after vaccination: RR 1.95 (95% CI: 0.85 to 4.48)\n–Within 7 to 10 days after vaccination: RR 1.69 (95% CI: 0.93 to 3.07)\n•ProQuad studiesᵻ:\n–Within 0 to 42 days after vaccination:  RR 1.30 (95% CI: 1.17 to 1.44) \n–Within 7 to 10 days after vaccination:  RR 2.01 (95% CI: 1.70 to 2.38) \n* Four studies are dose 1; One study includes children ages 4 -6 years who received dose 2; ᵻ Includes one study of children ages 4 -6 years who received dose 2. \nDi Pietrantonj  C, Rivetti A, Marchione P, Debalini  MG, Demicheli  V. Vaccines for measles, mumps, rubella, and varicella in children. Cochrane Database Syst Rev . 2021;11(11):CD004407. \nPublished 2021 Nov 22. doi:10.1002/14651858.CD004407.pub5 15\nSummary of evidence for febrile seizure risk after\nfirst dose of MMRV vaccination\n•Post -licensure studies assessed rates of febrile seizures in children aged 12 -\n23 months who received dose 1 MMRV vaccine and compared these rates \nwith children who received separate dose 1 injections of MMR and varicella \nvaccines at the same visit. \n•The studies used different methods, populations of children, and different \nformulations of MMRV. \n•Despite these differences, studies show remarkable consistency in findings\n16\nConclusion:  Evidence for febrile seizure risk after first \ndose MMRV vaccination\n•During the 6 weeks after vaccination, an increased risk for febrile seizures \nafter dose 1 MMRV compared with dose 1 MMR+V is only present during \nthe 1 -2 weeks after vaccination\n•The risk of febrile seizures occurring during other periods after \nvaccination is similar between dose 1 MMRV and MMR+V\nKlein NP, Fireman B, Yih WK, et al. Measles -mumps- rubella -varicella combination vaccine and the risk of febrile seizures. Pediat rics. 2010 Jul;126(1):e1 -8.\n17\n18Febrile Seizures following second dose of MMRV\nRisk of febrile seizures and fever following second \ndose of MMRV vaccine\n•Risk for febrile seizures is lower among children aged 4 -6 years than \namong children aged 12- 15 months\n•Prelicensure trials:\n-Lower fever rates in children aged 15 -31 months receiving dose 2 MMRV \ncompared with dose 1 MMRV (N=1035)1\n-Similar fever rates in children aged 4 -6 years receiving dose 2 MMRV (N=397) \ncompared with dose 2 MMR + varicella vaccines (N=193)2 \n1 Merck ProQuad  package insert, 2024\n2 Reisinger KS, et al. Brown ML, Xu J, et al. A combination measles, mumps, rubella, and varicella vaccine (ProQuad ) given to 4 - to 6-year -old healthy children vaccinated previously with \nMM- RII and Varivax  . Pediatrics. 2006;117(2):265 -272.19\nMerck -sponsored study findings of febrile seizures \nfollowing second dose of MMRV and MMR+V \n•Among children aged 4- 6 years:\n-No febrile seizures occurred during the 5- 12 days post -vaccination\n•22,212 children receiving second dose MMRV vaccine\n•24,778  children receiving second dose of MMR + V vaccine at same visit\nMarin, M, et al. Use of Combination Measles, Mumps, Rubella, and Varicella Vaccine: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR May 7, 2010/59(RR03);1 -1220\nVSD findings for all seizures after second- dose of \nmeasles -containing vaccine identified from electronic \nmedical records for children aged 4- 6 years\nKlein NP, et al. Measles -containing vaccines and febrile seizures in children age 4 to 6 years. Pediatrics. 2012 May;129(5):809 -14.\n21\n-Very few seizures identified by ICD -9 codes in electronic data \nVSD findings of chart -confirmed febrile seizures 7 to 10 \ndays after second dose of measles -containing \nvaccination for children aged 4–6 years, 2000 –2008\n•Electronic medical record review of the 4 post- MMRV seizures:\n-Febrile seizure: 1\n-Afebrile seizures:  2\n-Improbable seizure: 1\n22\n Klein NP, et al. Measles -containing vaccines and febrile seizures in children age 4 to 6 years. Pediatrics. 2012 May;129(5):809 -14.\nRisk of febrile seizure after second dose of MMRV: \nSystematic review and meta -analysis\n•Pre-licensure studies:\n•Po\n•Post -licensure study:\n-Only included one study of children 4-6 years; no evidence to suggest elevated risk of febrile seizure \n23Ma SJ, et al. . Risk of febrile seizure after measles -mumps -rubella -varicella vaccine: A systematic review and meta -analysis. Vaccine . 2015;33(31):3636 -3649.\n\nConclusion:  No evidence for febrile seizure risk after \ndose 2 MMRV vaccination\n•Among children aged 4- 6 years\n-Data do not suggest that children who receive dose 2 MMRV have an increased \nrisk of febrile seizures after vaccination compared with those who receive dose 2 \nas MMR + varicella vaccination at the same visit\nMarin, M, et al. Use of Combination Measles, Mumps, Rubella, and Varicella Vaccine: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR May 7, 2010/59(RR03);1 -12\n24\nConclusion\n•There is a small increased risk for febrile seizures after  first dose of MMR \nand MMRV vaccines \n•The risk is slightly higher with MMRV combination vaccine after the first \ndose\n-Studies have shown a small increased risk for febrile seizures during the 5 - 12 \ndays after a child has received their first vaccination with MMR vaccine \n-Studies have not shown an increased risk for febrile seizures after the varicella \nvaccine \n•There is no increased risk of febrile seizures after vaccination \nwith MMRV vaccine in children aged 4 through 6 years\n25\nQuestions?\nFor more information, contact CDC\n1-800- CDC- INFO (232 -4636)\nTTY:  1 -888- 232- 6348    cdc.gov atsdr.cdc.gov \nFollow us on X (Twitter) @CDCgov & @CDCEnvironment\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position \nof the U. S. Centers for Disease Control and Prevention and the Agency for Toxic Substances and Disease Registry.\n26", "summary": "Febrile Seizures following Measles, Mumps, Rubella,  and Varicella (MMRV) vaccine John Su Acting Director Immunization Safety Office Centers for Disease Control and Prevention September 18, 2025 September 2025:  Request to CDC from ACIP Chair Presentation on febrile seizures post administration of MMRV vs.  simultaneous administration of separate MMR and Varicella vaccines, by  two different age groups, 1 –2 and 4– 6-year -olds. Please use data both from  randomized trials and from the Vaccine…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-september-18-19-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-09-18-19/03-su-mmrv-508.pdf", "doc_date": "2025-09-18", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 26}
{"title": "hep b birth dose briefing 508", "content": "1 \n ACIP Meeting Materials for Public Posting:  Hepatitis B Birth Dose Briefing Document  \n \nContents  \n1. Background  \n2. Epidemiology  \n3. Systematic Review s for studies  on hepatitis B birth dose vaccine  \n4. Appendices  \nAppendix 1 ACIP Recommendations  \nAppendix 2 Global Recommendations  \n \n1. Background  \n \nIntroduction  \nHepatitis B virus (HBV) infection can be transmitted from mother -to-child during pregnancy and delivery. \nWithout any interventions, up to 85% of infants born to women with HBV infection acquire HBV \ninfection. Perinatal ly acquired  HBV infection has severe health and economic consequences : about 90% \nof infants perinatally infected with HBV will develop chronic hepatitis B, and 25% of people infected with \nHBV during childhood will die prematurely due to HBV-related complications  including liver cirrhosis and \nliver cancer . (1, 2)  \n \nUp to 2.4 million people in the United States are estimated to have hepatitis B; about half of people with \nhepatitis B in the U.S. are  unaware of their infection. About 75% of people with chronic hepatitis B in the \nUnited States  were born in counties with intermediate and high prevalence of hepatitis B  and \npredominantly were infected at birth  or during early childhood . In the United States, decades of evolving \nhepatitis B vaccination recommendations  among infants and children have shifted the epidemiology of \nacute hepatitis B cases from children to unvaccinated adults . In 2023, 14,400 acute hepatitis B cases \nwere estimated to occur in the U.S., with the highest rates among adults aged 40 -59 years; among \nreported cases of acute hepatitis B, only 26% reported an associated risk behavior, with 28% reporting \nno risk, and 4 6% missing data on risk factors. Unlike children, adults who acquire new HBV infection have \nhigher viral clearance rates  and lower risk for developing chronic infection. (3-9) \n \nHepatitis B vaccination is the cornerstone of hepatitis B prevention and control.  The hepatitis B vaccine is \nthe first anti -cancer vaccine and has been available in the United States for more than 40 years. Two \ntypes of products are available for prophylaxis against  perinatal  HBV infection: hepatitis B vaccine, which \nprovides long -term protection against HBV infection and is recommended for both preexposure and  \npostexposure prophylaxis; and hepatitis B immune globulin (HBIG), which provides temporary protection \nand is indicated only in certain postexposure settings.  Two single -antigen h epatitis B recombinant \nvaccines are FDA -approved for the vaccination of persons starting at birth in the U.S.: Recombivax HB, \napproved in  1986 and Engerix -B, approved in 1989 . Hepatitis B vaccination is a multi dose series , typically \nconsisting of 3 doses, with increasing s eroprotection after each dose. Three doses of hepatitis B are \nneeded to ensure full protection  where 95% of healthy infants develop  a protective antibody response \n2 \n (anti -HBs ≥ 10  mIU/ mL). When administered shortly after birth  to infants born to HBsAg -positive women , \nhepatitis B vaccination and HBIG reduce mother -to-child transmission by 94%. (1, 10 -13) \n \nPrevention of perinatal or early life HBV infection underpins the recommendation  for hepatitis B \nvaccination starting at birth.  Since 1988, u niversal hepatitis B screening (with HBsAg) has been \nrecommended for all pregnant women in the first trimester of pregnancy , as has testing later in \npregnancy for women with risk behaviors  and testing at delivery for women whose hepatitis B status is \nunknown. Hepatitis B vaccination has been recommended  at birth for all infants born to women known \nto have HBV infection since 198 4 (specified to within 12 hours of birth in 1988),  and among all infants \nborn to women with unknown hepatitis B status since 1991.  Hepatitis B immune globulin has been \nrecommended to be administered  within 12 hours of  birth for all infants born to women known to have \nHBV infection since 198 4, and among infants born to women with unknown hepatitis B status since \n2018.  In 1991, the US adopted a strategy for u niversal h epatitis B vaccination  of all  infants . Beginning in \n2005, the first dose of hepatitis B vaccine among infants born to HBsAg -negative women was \nrecommended to be administered at the birth hospital ; this was updated in 2018 to specify within 24 \nhours of birth . (1, 14 -20) \n \nIn the context of these evolving hepatitis B vaccination recommendations among newborns and children, \nthe number of reported US cases of acute hepatitis B has dropped 88% from 1991 (18,003 cases) to 2023 \n(2,214 cases). The United States’ comprehensive strategy to prevent  hepatitis B is based on : 1) routine \ntesting of all pregnant women for HBsAg ; 2) post exposure  prophylaxis within 12 hours of birth with \nhepatitis B vaccine and HBIG of all infants born to women who are HBsAg -positive or HBsAg -status \nunknown ; 3) universal vaccination of all infants beginning at birth; 4) routine vaccination of previously \nunvaccinated children, adolescents, and adults aged 19 -59 years ; and 5) vaccination of all adults at risk \nfor HBV infection or who request vaccination . (1, 9, 20, 21)  \n \nTransmission , Natural History of Disease , and Associated Healthcare Costs  \nHBV transmission occurs through percutaneous or mucosal exposure to infectious blood or body fluids . \nThe virus  can remain viable for over 7 days on environmental surfaces at room temperature. The two \nprimary sources of HBV infection among children are perinatal transmission from mothers with hepatitis \nB and horizontal transmission from infected household contacts.  Prior to the widespread availability of \npostexposure prophylaxis  (i.e., vaccine and HBIG  within 12 hours of birth ), the proportion of infants born \nto HBsAg -positive women who acquir ed HBV infection was as high as 85%. Children living with a person \nwith chronic HBV infection in a household or community setting are also at risk and transmission rates \nhave ranged to up to 11% in US settings. (1, 22 -24) \n \nYoung children with acute hepatitis B rarely have symptoms, but 90% of infants who are infected with \nHBV become chronically infected . In contrast, among persons 5 years of age and older , fewer t han 5%  \ndevelop chronic infection . Since the risk of chronic infection increases with decreasing age, people who \nare infected in early childhood experience a disproportionately higher burden of disease attributable to \nchronic HBV infection. About 25% of individuals chronically infected during childhood will develop end \n3 \n stage liver disease or liver cancer and die prematurely.  Fulminant hepatitis occurs in ≤1% of acute \ninfections, but the incidence of fulminant hepatitis B is higher in infancy than in other pediatric age \ngroups . (1, 8, 21, 25 -28) \n \nChronic HBV infection  can progress to cirrhosis, hepatocellular carcinoma (HCC), liver transplant, and \ndeath. Based on US cancer data from the Surveillance, Epidemiology and End Results (SEER) Program, \nover 38,000 HCC cases were forecasted for 2020 and over 56,000 HCC cases we re forecasted for 2030. \nHBV is an important cause of HCC, with 10% to 15% of patients with HCC attributed to HBV  infection . The \nburden of US hepatitis B related hospitalizations is significant; each year, more than $1 billion is spent on \nhepatitis B -relate d hospitalizations, not including indirect costs such as poor quality of life, reduced \neconomic productivity, long -term disability, and premature death. The estimated annual costs of treating \none patient with hepatitis B in the United States, adjusted for inflation are up to $93,935 for those with \nless severe disease and up to $324,849 for those requiring liver transplant.  (2, 29 -33) \n \nHepatitis B is Vaccine Preventable with Robust Seroprotection  \nHepatitis B vaccination is the most effective measure to prevent HBV infection and its consequences . The \nplasma -derived hepatitis B vaccine was licensed in 1981; recombinant hepatitis B vaccines replaced the \nplasma -derived vaccines in the U.S. by the late 1980’s.  Hepatitis B  recombinant vaccines  are available as \na single -antigen formulation and in combination with other vaccines. Two single -antigen vaccines \nrecommended for use in the United States, Engerix -B and Recombivax HB, are used for the vaccination of \npersons starting at birth. An extensive  body of literature resulting from over more than 40 years of use  in \nthe United States and other countr ies demonstrates that the hepatitis B vaccines are safe and effective in \nprotecting infants from hepatitis B.  (1) \n \nThe efficacy of the hepatitis B  vaccine alone in preventing perinatal transmission is ~75%. Hepatitis B \nimmunoglobulin provides passively acquired anti -HBs and temporary protection (i.e., 3 –6 months) and is \ngenerally used as an adjunct to hepatitis B vaccine in infants born to HBsAg -positive mothers and in \ncertain other postexposure prophylaxis situations. The efficacy of HBIG alone is around 71%. When \ncombined with the hepatitis B  vaccine, the efficacy of HBIG and hepatitis B birth dose (HepB -BD) vaccine \nis 94%. The sooner the HepB -BD vaccine is provided after birth, the greater its effectiveness in \npreventing perinatal transmission. The optimal recommended timing is to provide the vaccine within 24 \nhours of birth , accelerated to  within 12 hours if the maternal HBsAg status is p ositive or unknown.  \nUnvaccinated infants remain at risk of non -perinatal HBV acquisition  through exposure to a  person with \nHBV infection in a household or community  setting .  HepB -BD provides protection for infants at risk from \nhousehold exposure after the perinatal period. (1, 23, 24, 34, 35)  \n \nAmong health y infants, 25% and 63% achieve protective hepatitis B surface antibody levels after the first \nand second dose, respectively , however full protection is only achieved with the complete vaccine series .  \nThe 3 -dose hepatitis B  vaccine series produces a protective antibody response in 98% of healthy term \ninfants, and 95% of healthy infants overall. Seroprotection from vaccination lasts for decades. In one \n4 \n Alaska -based study, over 90% of primary responders were estimated to have protective immunity for \nmore than 30 years after vaccination. (1, 11, 13, 28, 36 -40)  \n \nHepatitis B Birth Dose Provides a Critical Safety Net in the Preve ntion of Perinatal and Early Childhood \nTransmission  \nUniversal  HepB -BD provides a critical safety net for infants who may have unrecognized exposure(s) to \nHBV infection during pregnancy or early childhood  due to a multitude of reasons  resulting in gaps in \nprotection against perinatal infection.  Reasons for missed opportunities to prevent perinatal \ntransmission include lack of prenatal care,  where overall 15% of pregnancies receive inadequate or no \nprenatal care  (where inadequate care is defined a s care after the 4th month of pregnancy and includes \nless than 50% of visits) . Additionally , missed opportunities arise from  gaps in maternal screening \nimplementation, incorrect screening tests performed, errors in interpreting the screening test or the \ntranscription of the screening test , lapses in providing standard of care post exposure prophylaxis , and \nacute /window period infection . Gaps in perinatal HBV testing during  pregnancy indicate 12 -16% of \npregnant women in the United States  had no record of being test ed for HBsAg, with lower testing rates \namong Medi caid-enrolled women. Further, d espite a robust national perinatal hepatitis B prevention \nprogram, the program identifies less than one -half of infants estimated to be born to HBsAg -positive \nwomen each year, highlighting a critical gap in identifying perinatally  exposed infants . Case reports of  the \nmedical  outcomes  for perinatally exposed infants demonstrate the catastrophic impact when universal \nHepB -BD is not fully implemented. (41-47) \n \nInfants who receive HepB -BD are more likely to complete their vaccination series and had a positive \nimpact on rates of being up to date for other age -appropriate vaccines . Additionally, there is a risk for \nhorizontal transmission in the household from persons who are not aware of their infection status; 50% \nof people in the US are unaware of their infection.  Universal HepB -BD is of critical importance and \nprovides a safety net for infants who may have unrecognized exposure(s) to HBV infection during \npregnancy or early childhood. (1, 3, 19, 25, 48, 49)  \n \n \n2. Epidemiology  \nShifting Epidemiology of Acute Hepatitis B in the U.S.  Reflects Success of Hepatitis B Vaccination \namong Newborns and Infants  \nThree decades  of evolving  hepatitis B vaccination recommendations among newborns and infants ha ve \nparalleled marked  reductions in acute hepatitis B cases in the United States. Following the introduction \nof recommendations for all infants born to HBsAg+ women to receive hepatitis B vaccination and HBIG \nwithin 12 hours of birth, the reported number of acute hepatitis B cases in the U.S. fell by 22% from \n23,177 in 1988 to 18,003 in 1991. Following the 1991 recommendations which included  provid ing \nhepatitis B vaccination within 12 hours of birth for infants born to women with unknown HBsAg status as \nwell as introducing universal hepatitis B vaccination for all infants, reported number of acute hepatitis B \ncases dropped another 69% from 1991 to 2005 ( 5,494 ). Finally, following the 2005 recommendation \nspecifying that  the first dose of infant hepatitis B vaccination occur prior to hospital discharge  and the \n5 \n further specification that the dose occur within the first 24 hours of life , the reported number  of acute \nhepatitis B  cases  fell an additional 60% from 2005 to 20 23 (2,214 ).  \nFigure 1  \n \n \nFrom 1991 through 2023, rates of reported cases of acute hepatitis B have decreased among all age \ngroups, with the lowest rates among persons <19 years of age and those aged 20 -29 years, indicating a \ngenerational impact of more than 3 decades of evolving h epatitis B vaccination recommendations \namong newborns and infants. (9, 17, 19, 21, 25, 50)  \n  \n\n6 \n Figure 2  Viral Hepatitis Surveillance Reports | Viral Hepatitis | CDC  \n \nReferences: CDC NNDSS Viral Hepatitis Surveillance : (https://www.cdc.gov/hepatitis/php/statistics -\nsurveillance/index.html ); (4, 9, 21)  \n \n3. Updated Rapid Systematic Review for studies on hepatitis B birth dose vaccine within 24 hours of \nbirth  \nIn response to the request from the ACIP Chair to provide “ results from randomized trials concerning the \nadministration of the HepB vaccine within 24 hours of birth, with all results stratified by the HepB \ninfection status of the mother. Include both efficacy data and adverse events, including all -cause \nmorbidity a nd mortality. For children whose mothers are HepB negative, present results for all children \ncombined as well as stratified by pre -mature birth and birth weight. If randomized data is lacking for any \nof the requested populations, please mention that ”, an updated rapid systematic review (URSR) for \nstudies on hepatitis B birth dose (HepB -BD) vaccination within 24 hours of birth was conducted spanning \n12/17/2011 – 8/14/2025,  building on an existing systematic review  (ESR)  (28) spanning 1/1/1987 – \n12/16/2011.  \nThe inclusion criteria  for the review included studies for  newborn infants receiving a  monovalent  \nhepatitis B vaccine within 24 hours of birth  for a list  of outcomes ( seroprotection , efficacy,  safety , \nmorbidity and mortality). The definitions and timepoints for seroprotection, efficacy, and safety \noutcomes are as follows: s eroprotection is defined as  anti -HBs ≥10 mIU/mL mL at least 1 -2 month s after \nthe final dose in the vaccine series or between 9 -12 months of age and is the first time point reported \nimmediately following the last dose in a vaccine series; efficacy is defined as HBsAg and/or HBV DNA \npositivity at the latest available timepoint ; safety is reported by local and systemic adverse events and is \nreported at birth or the closest time point immediately after the birth dose.  Morbidity is defined as \nsevere illness or hospitalization and mortality is defined as death.  \n\n7 \n The ESR search (n=833) and the URSR (n=1380) were further assessed using the inclusion criteria \nfocused on the ACIP request. Seventeen studies met the inclusion criteria  (7 from the ESR and 10 from \nthe URSR). The 17 studies were grouped by efficacy trials,  timing of the vaccination, product or \nformulation differences , dose and schedule , and HBIG co -intervention for the specified outcomes of \ninterest (seroprotection, efficacy and safety outcomes). The two HBIG co -intervention trials were \nreviewed but not inc luded in the briefing document since these  studies did not address the question .  \nOther intervention characteristics included the vaccine type administered (Engerix, Recombivax or other \nhep B vaccines), dose and schedule.  \nAcross intervention study types (timing of vaccination (birth vs 18 months); efficacy trials; product and \nformulation; dose of vaccine and schedule) meeting the rapid systematic review inclusion criteria  can be \nsummarized as:  \n• Hepatitis B vaccine series first administered at birth achieved high levels of seroprotection in \ninfants born to HBsAg -positive women  and HBsAg -negative women;  \n• Among infants born to HBsAg -positive mothers, hepatitis B birth dose vaccin ation demonstrated \nefficacy in the prevention of perinatal transmission ;  \n• Hepatitis B birth dose  vaccine  is safe and resulted in few local and systemic adverse effects, \nincluding infants born to HBsAg -negative mothers ; and  \n• Head -to-head comparisons of various hepatitis B recombinant vaccine products, doses, and \nschedule show ed no meaningful differences in reported outcomes . \nThe URSR did not identify placebo -controlled trials assessing efficacy; given that the efficacy of the HepB \nvaccine was established in the 1980s and 1990s , this is unsurprising as  it is unethical to withhold a \nproven, safe and effective intervention simply to include a placebo group . There were  also limited \nreporting outcomes for preterm, low birth weight and extremely low birthweight infants, as well as for \nmorbidity and mortality. Bias was assessed using the Cochrane Risk of Bias, version 2 (RoB 2) (51). This \ntool assesses  risk of bias in RCTs related to  the following domains : randomization process, deviation from \nintended intervention, missing outcome data, measurement of outcome and selection of reported \nresults . Of note, many of the studies were done before the wide application of the CONSORT statement  \n(52), which seeks to improve reporting of randomized controlled trials (RCTs)  Most of the RCTs (59%) \nassessed had a high risk of overall bias primarily due to the  domains of randomization and measurement \nof outcomes . In summary, the body of evidence from the ESR and the URSR support the findings that:  \n• Hepatitis B birth dose induces high seroprotection and efficacy ; \n• Hepatitis B birth dose vaccine is safe ; and  \n• Head -to-head comparisons of various hepatitis B recombinant vaccine products, doses, and \nschedule show no meaningful differences  in reported outcomes in efficacy and safety . \n \n \n  \n8 \n Appendix 1   \nHepatitis B screening recommendations for pregnant women and ACIP hepatitis B vaccination \nrecommendations for infants, United States, 198 4-2022.  \n \nModified from Bixler PHR 2023, Suppl Table 2.  \nACIP = Advisory Committee on Immunization Practices; HBIG = hepatitis B immune globulin; HepB, hepatitis B \nvaccine.   \n*Only single -antigen HepB vaccine should be used for the birth dose.  \nNote: All hepatitis B birth dose vaccinations are considered to be the first dose of the infant series except among \npre-term infants weighing <2,000 grams who are born to mothers who are HBsAg positive.  \n1. CDC. MMWR Morb Mortal Wkly Rep 37, 341 -346, 351 (1988).  \n2. CDC. MMWR Morb Mortal Wkly Rep 33, 285 -290 (1984).  \n3. CDC. Update on hepatitis B prevention. MMWR Morb Mortal Wkly Rep 36, 353 -360, 366 (1987).  \n4. CDC. Recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR Recomm Rep \n40, 1 -25 (1991).  \n5. Schillie, S. et al. MMWR Recomm Rep 67, 1 -31 (2018).  \n6. Mast, E. E. et al. MMWR Recomm Rep 54, 1 -31 (2005).  \n7. Bixler D et al. Public Health Rep. 2023 Jun 9  \n \n\n9 \n Appendix 2  \nGlobal hepatitis B v accination policies and prevalence in pregnant women  \nGlobal Hepatitis B Birth Dose Vaccination Policies  \nIn 1987, the WHO Hepatitis and Immunization Technical Advisory group s emphasized the importance of \nhepatitis B vaccination to control infections globally  and recommended hepatitis B vaccination in infancy \nfocusing on countries where HBsAg prevalence was higher than 2% . In 2004, the WHO recommended \nhepatitis B birth dose vaccination as soon as possible after birth (within 24 hours) focusing on countries \nwith intermediate and high endemicity (HBsAg  prevalence >2%) while also recommending hepatitis B \nvaccination  in low endemicity settings especially to infants born to HBsAg positive mothers. In 2009 and \nthen in 2017, the WHO Strategic Advisory Group of Experts reevaluated  the data and base d on evidence \nto recommendations analysis, recommended universal hepatitis B birth dose vaccination as soon as \npossible after birth, preferably within 24 hours of birth , followed by completion of 3 or 4 dose hepatitis B \nvaccination series  among all infants  in all countries irrespective of HBsAg prevalence . Those vaccination \nrecommendations  have evolved based on global goals which focused in the 1990s and early 2000s on \ncontrolling  hepatitis B through scale up of childhood immunization and then progressed  in 2015 to focus \non eliminating viral hepatitis as a public health threat  by 2030 through the scale up of prevention, \nscreening and treatment . The United States has endorsed the global goals of elimination of viral hepatitis  \nby 2030  and developed national strategies to achieve the targets .  \nGlobally , of the 194 WHO  member states, 116 countries recommend universal hepatitis B birth dose \nvaccination to all newborns , in alignment with global recommendations. Relatively f ew countries (3 3) \nprovide selective hepatitis B birth dose to infants born to mothers who are either HBsAg -positive o r of \nHBsAg -unknown status . Two countries have partially introduced universal HepB -BD. In Canada , New \nBrunswick, the Northwest territories and Nunavut provide universal HepB -BD while other provinces \nprovide selective HepB -BD. Pakistan introduced universal HepB -BD in two of its most populated \nprovinces (Punjab and Sindh).   \nThe 43 c ountries that have not introduced HepB -BD are mostl y countries  in Sub -Saharan Africa , but this \nis changing and in 2024, many countries  have either initiated introduc tion this year  or expressed interest \nin introducing HepB-BD in their immunization schedule  in the next 3 -5 years .  \n10 \n Map : Hepatitis B vaccine birth dose vaccination policy by county, 2025  \n \nSources: Provincial and territorial routine and catch -up vaccination schedule for infants and children in Canada - \nCanada.ca ; Hepatitis B vaccine – NHS ; Vaccine Scheduler | ECDC ; 9. Hepatitis B – Health New Zealand | Te Whatu \nOra; Introduction of Hepatitis B vaccine ; Hepatitis B | The Australian Immunisation  Handbook ; \n20240220_Immunization_Schedule_english.pdf ; National Immunization Program for children | Policy&Services  : \nKDCA ; Hepatitis B  \nUniversal HepB -BD:  Hepatitis B birth dose  vaccine  provided to all newborns .  \nSelective HepB -BD:  Hepatitis B birth dose vaccine provided only to infants  born to women who test positive for \nHBsAg.  \nPartially  introduced universal HepB -BD:  Hepatitis B vaccine strategy among infants  varies by geographic location \nwithin the country.  \n \nBased on the request from the ACIP chair, we analyzed hepatitis B vaccination policies and schedule in 37 \ncountries which include , Canada, countries in the European Union  (EU)  (n=27)  and European Economic \nArea (EEA ) (Iceland, Liechtenstein, and Norway ), the United Kingdom  (UK) , Switzerland, Australia, New \nZealand, South Korea and Japan and compared them to the United States.  \nAmong infants born to women with known HBV infection  (HBsAg positive women) , the  U.S. is aligned \nwith  Canada, all EU /EEA countries ,  the United Kingdo m (UK), Switzerland, Australia, New Zealand, South \nKorea and Japan  which  all recommend the hepatitis B birth dose to be given at birth simultaneously with \nHBIG , either before discharge from the hospital or within 24 hours of birth.   \n\n11 \n For infants born to  HBsAg -negative women , countries with a universal hepatitis B birth dose vaccination \npolicy give all children the first dose following the same schedule as children born to HBsAg positive \nmothers.  \nAmong the 37 countries assessed,  26 implement selective HepB -BD for infants born to HBsAg -positive \nwomen  and the universal infant vaccination with three doses of hepatitis B vaccine to all infants \nirrespective of mothers ’ HBsAg status . Children born to HBsAg -negative mothers receive the first dose of \nhepatitis B vaccine by 3 months of age in 24 of the 26 countries  (18 countries at 2 months of age and 6 \ncountries at 3 months of age) . \nTable: age at receipt of first dose of hepatitis B vaccine in selected countries *  \n \n*United States, Canada, all EU/EEA countries, UK, Norway, Switzerland, Iceland, Australia, New Zealand, South \nKorea and Japan.  \nSources: Provincial and territorial routine and catch -up vaccination schedule for infants and children in Canada - \nCanada.ca ; Hepatitis B vaccine – NHS ; Vaccine Scheduler | ECDC ; 9. Hepatitis B – Health New Zealand | Te Whatu \nOra;  The Australian Immunisation  Handbook ; 20240220_Immunization_Schedule_english.pdf ; National \nImmunization Program for children | Policy&Services  : KDCA ; Hepatitis B  \nHigh -income  countries base their decisions on vaccination schedule using cost -benefit and cost -\neffectiveness assessments , especially countries  that provide free universal health care , along with \nepidemiological profile and high levels of maternal hepatitis B screening in the population. For example , \nin 2016 -2017, Japan and the United Kingdom switched from selective infant hepatitis B vaccination to \nuniversal infant vaccination after reviewing country -specific  epidemiological and cost -effectiveness data.  \nIn 2020, Slovenia switched from providing the first dose of hepatitis B at school entry to providing \nuniversal hepatitis B infant vaccination starting at 3 months of age.  To date, n o country in the world has \nreverted  from universal to selective hepatitis B vaccination schedules.  \n  \n\n12 \n Hepatitis B prevalence  and screening  in pregnant women  \nBased on the request from the ACIP chair, we analyzed hepatitis B prevalence and screening among \npregnant women in  37 countries which include: Canada, countries in the European Union (EU) (n=27) \nand European Economic Area (EEA) (Iceland, Liechtenstein, and Norway), the United Kingdom (UK), \nSwitzerland, Australia, New Zealand, South Korea and Japan and compared them to  the United States.  \nPrevalence estimates of hepatitis B among pregnant women were available in 20 of the 37 assessed \ncountries. Overall, 9 countries had less than 0.5% prevalence of hepatitis B surface antigen among \npregnant women while 8 countries reported a prevalence ranging from 0.5 to 0.9% and 3 countries \nreported a prevalence greater than 2% in pregnant women.  There are no data on the prevalence of \nhepatitis B in pregnant women in the United States in the last 10 years.  \nOnly 6 of the 3 7 selected countries have national registries that can track hepatitis B screening among \npregnant women and estimate prevalence on an annual basis. The other 31 countries and the United \nStates  do not track hepatitis B screening during pregnancy. In those countries, hepatitis B prevalence \nestimates when available  are based on surveys or special studies completed in previous years.  \nFigure: Prevalence of hepatitis B surface antigen  among pregnant women  in selected countries*  \n \n \n* United States, Canada, all EU/EEA countries, UK, Norway, Switzerland, Iceland, Australia, New Zealand, South \nKorea and Japan.  \nSources: Hepatitis B in England 2024 - GOV.UK ; Hepatitis B and C in Pregnancy and Children: A Canadian \nPerspective – PMC ; Evidence brief - prevention of hepatitis B and C in Europe and the UK ; Uptake of perinatal \nimmunoprophylaxis  for infants born to women with a record of hepatitis B in Victoria (2009 –2017) – ScienceDirect ; \nUpdated -National Hepatitis Elimination Profile - Switerland -July2023_0.pdf ; Gaps in Prenatal Hepatitis B Screening \nand Management of HBsAg Positive Pregnant Persons in the U.S., 2015 –2020 - PMC  \nAll of the 37 selected countries, except two, provide universal health care access to all citizens (includ ing \nresidents and migrants) . \n\n13 \n Of the 29 countries that provide selective HepB -BD, five countries have national registries that can track \nthe percentage of pregnant women screened for hepatitis B and subsequent care cascade of mother and \ninfant. The remaining countries either have systems similar to the  perinatal hepatitis B  prevention \nprogram in the  U.S. or report positive hepatitis B test results to a national notifiable disease surveillance \nsystem . Unlike countries that provide selective HepB -BD, the United States does not have universal \nhealthcare coverage with free access to antenatal care and vaccinations to the population. This is a \ncritical difference between the United States and the countries that provide selective HepB -BD. \nAs a result  of lack of adequate systems  to track screening in pregnant women and subsequent post -\nexposure prophylaxis  in exposed infants , most of the countries with selective HepB -BD policies cannot \ntrack whether they are succeeding in preventing perinatal transmission of hepatitis B  on a regular basis  \n(outside of special studies) . However, they provide universal healthcare to all the population with access \nto free antenatal care and vaccination services.  \nTo highlight the limited data availability in the 37 assessed countries, we compiled publicly available data \non the percentage of pregnant women who are screened for hepatitis B surface antigen during \npregnancy in each of those countries. Of the 37 countries selected to compare to the United States, only \n19 had publicly available data on percentage of pregnant women screened for hepatitis B.  Overall, 15  \ncountries reported that more than 90% of pregnant women are screened  for hepatitis B , which is the \n2030 g lobal indicator for validation of elimination.  The United States is one of five countries not meeting \nthe 2030 global screening target . All countries that provide selective hepatitis B birth dose vaccination \nthat have available antenatal screening data  have achieved the 90% global antenatal screening coverage \ntarget for hepatitis B.  \nFigure: Coverage of antenatal screening for hepatitis B in selected countries  \n \n \n*No universal healthcare coverage  \n2023 data except for the following countries:  Lithuania, 2021; United States, 2015 -2019; France, Germany, and Poland, \ndata >5 but <10 years old.  \nNo data is publicly available for Austria, Belgium, Croatia, Cyprus, Greece, Iceland, Italy, Japan, Latvia, Lichtenstein, \nLuxembourg, Malta, New Zealand, Norway, Romania, South Korea, Spain, or Sweden.  \n \n14 \n  \nSources: Hepatitis B in England 2024 - GOV.UK ; Hepatitis B and C in Pregnancy and Children: A Canadian \nPerspective – PMC ; Evidence brief - prevention of hepatitis B and C in Europe and the UK ; Uptake of perinatal \nimmunoprophylaxis  for infants born to women with a record of hepatitis B in Victoria (2009 –2017) – ScienceDirect ; \nUpdated -National Hepatitis Elimination Profile - Switerland -July2023_0.pdf ; Gaps in Prenatal Hepatitis B Screening \nand Management of HBsAg Positive Pregnant Persons in the U.S., 2015 –2020 - PMC  \n \nReferences  \n1. Schillie S, Vellozzi C, Reingold A, Harris A, Haber P, Ward JW, et al.  Prevention of \nHepatitis B Virus Infection in the United States: Recommendations of the Advisory \nCommittee on Immunization Practices. MMWR Recomm Rep. 2018;67(1):1 -31. \n2. Nguyen MH, Burak Ozbay A, Liou I, Meyer N, Gordon SC, Dusheiko G, et al.  \nHealthcare resource utilization and costs by disease severity in an insured national \nsample of US patients with chronic hepatitis B. J Hepatol. 2019;70(1):24 -32. \n3. Bixler D, Barker L, Lewis K, Peretz L, Teshale E . Prevalence and awareness of \nHepatitis B virus infection in the United States: January 2017 - March 2020. Hepatol \nCommun. 2023;7(4).  \n4. CDC. Viral Hepatitis Surveillance Report – United States, 2022. \nhttps://www.cdc.gov/hepatitis -surveillance -2022/hepatitis -b/figure-2-7.html; 2022.  \n5. Razavi-Shearer D, Gamkrelidze I, Pan CQ, Razavi -Shearer K, Blach S, Estes C, et al.  \nThe impact of immigration on hepatitis B burden in the United States: a modelling \nstudy. Lancet Reg Health Am. 2023;22:100516.  \n6. Roberts H, Ly KN, Yin S, Hughes E, Teshale E, Jiles R . Prevalence of HBV Infection, \nVaccine-Induced Immunity, and Susceptibility Among At -Risk Populations: US \nHouseholds, 2013 -2018. Hepatology. 2021;74(5):2353 -65. \n7. Wong RJ, Brosgart CL, Welch S, Block T, Chen M, Cohen C, et al.  An Updated \nAssessment of Chronic Hepatitis B Prevalence Among Foreign -Born Persons Living \nin the United States. Hepatology. 2021;74(2):607 -26. \n8. CDC. Epidemiology and Prevention of Vaccine -Preventable Diseases Pink Book - \nChapter 10 Hepatitis B. In: Hall E. WAP, Hamborsky J., et al., ed. 14 ed. Washington, \nD.C. : Public Health Foundation; 2021.  \n9. CDC. Viral Hepatitis Surveillance Report – United States, 2023. \nhttps://www.cdc.gov/hepatitis -surveillance -2023/about/index.html ; 2025.  \n10. CDC. Update: expanded availability of thimerosal preservative -free hepatitis B \nvaccine. MMWR Morb Mortal Wkly Rep. 2000;49(28):642, 51.  \n11. Beasley RP, Hwang LY, Lee GC, Lan CC, Roan CH, Huang FY, et al.  Prevention of \nperinatally transmitted hepatitis B virus infections with hepatitis B immune globulin \nand hepatitis B vaccine. Lancet. 1983;2(8359):1099 -102.  \n12. Beasley RP, Trepo C, Stevens CE, Szmuness W . The e antigen and vertical \ntransmission of hepatitis B surface antigen. Am J Epidemiol. 1977;105(2):94 -8. \n13. Lee C, Gong Y, Brok J, Boxall EH, Gluud C . Effect of hepatitis B immunisation in \nnewborn infants of mothers positive for hepatitis B surface antigen: systematic \nreview and meta -analysis. BMJ. 2006;332(7537):328 -36. \n15 \n 14. CDC. Postexposure prophylaxis of hepatitis B. MMWR Morb Mortal Wkly Rep. \n1984;33(21):285 -90. \n15. CDC. Update on hepatitis B prevention. MMWR Morb Mortal Wkly Rep. \n1987;36(23):353 -60, 66.  \n16. CDC. Prevention of perinatal transmission of hepatitis B virus: prenatal screening of \nall pregnant women for hepatitis B surface antigen. MMWR Morb Mortal Wkly Rep. \n1988;37(22):341 -6, 51.  \n17. CDC. Hepatitis B virus: a comprehensive strategy for eliminating transmission in the \nUnited States through universal childhood vaccination. Recommendations of the \nImmunization Practices Advisory Committee (ACIP). MMWR Recomm Rep. \n1991;40(RR -13):1-25. \n18. CDC. Prevention of perinatal hepatitis B through enhanced case management --\nConnecticut, 1994 -95, and the United States, 1994. MMWR Morb Mortal Wkly Rep. \n1996;45(27):584 -7. \n19. Mast EE, Margolis HS, Fiore AE, Brink EW, Goldstein ST, Wang SA, et al.  A \ncomprehensive immunization strategy to eliminate transmission of hepatitis B virus \ninfection in the United States: recommendations of the Advisory Committee on \nImmunization Practices (ACIP) part 1: immunization of infants, children, and \nadolescents. MMWR  Recomm Rep. 2005;54(RR -16):1-31. \n20. Weng MK, Doshani M, Khan MA, Frey S, Ault K, Moore KL, et al.  Universal Hepatitis B \nVaccination in Adults Aged 19 -59 Years: Updated Recommendations of the Advisory \nCommittee on Immunization Practices - United States, 2022. MMWR Morb Mortal \nWkly Rep. 2022;71(13):477 -83. \n21. Bixler D, Roberts H, Panagiotakopoulos L, Nelson NP, Spradling PR, Teshale EH . \nProgress and Unfinished Business: Hepatitis B in the United States, 1980 -2019. \nPublic Health Rep. 2023:333549231175548.  \n22. Bond WW, Favero MS, Petersen NJ, Gravelle CR, Ebert JW, Maynard JE . Survival of \nhepatitis B virus after drying and storage for one week. Lancet. 1981;1(8219):550 -1. \n23. Franks AL, Berg CJ, Kane MA, Browne BB, Sikes RK, Elsea WR, et al.  Hepatitis B virus \ninfection among children born in the United States to Southeast Asian refugees. N \nEngl J Med. 1989;321(19):1301 -5. \n24. Hurie MB ME, Davis JP . Horizontal transmission of hepatitis B virus infection to \nUnited States -born children of Hmong refugees. Pediatrics. 1992;89(2):269 -73. \n25. Armstrong GL, Mast EE, Wojczynski M, Margolis HS . Childhood hepatitis B virus \ninfections in the United States before hepatitis B immunization. Pediatrics. \n2001;108(5):1123 -8. \n26. Chang MH . Hepatitis B virus infection. Semin Fetal Neonatal Med. 2007;12(3):160 -7. \n27. Chen HL, Chang CJ, Kong MS, Huang FC, Lee HC, Lin CC, et al.  Pediatric fulminant \nhepatic failure in endemic areas of hepatitis B infection: 15 years after universal \nhepatitis B vaccination. Hepatology. 2004;39(1):58 -63. \n28. Schillie SF, Murphy TV . Seroprotection after recombinant hepatitis B vaccination \namong newborn infants: a review. Vaccine. 2013;31(21):2506 -16. \n16 \n 29. Aly A, Ronnebaum S, Patel D, Doleh Y, Benavente F . Epidemiologic, humanistic and \neconomic burden of hepatocellular carcinoma in the USA: a systematic literature \nreview. Hepat Oncol. 2020;7(3):HEP27.  \n30. El-Serag HB . Epidemiology of viral hepatitis and hepatocellular carcinoma. \nGastroenterology. 2012;142(6):1264 -73 e1.  \n31. Nelson NP, Easterbrook PJ, McMahon BJ . Epidemiology of Hepatitis B Virus Infection \nand Impact of Vaccination on Disease. Clin Liver Dis. 2016;20(4):607 -28. \n32. Petrick JL, Kelly SP, Altekruse SF, McGlynn KA, Rosenberg PS . Future of \nHepatocellular Carcinoma Incidence in the United States Forecast Through 2030. J \nClin Oncol. 2016;34(15):1787 -94. \n33. Sorrell MF, Belongia EA, Costa J, Gareen IF, Grem JL, Inadomi JM, et al.  National \nInstitutes of Health Consensus Development Conference Statement: management \nof hepatitis B. Ann Intern Med. 2009;150(2):104 -10. \n34. Ruff TA, Gertig DM, Otto BF, Gust ID, Sutanto A, Soewarso TI, et al.  Lombok Hepatitis \nB Model Immunization Project: toward universal infant hepatitis B immunization in \nIndonesia. J Infect Dis. 1995;171(2):290 -6. \n35. Mahoney . Progress on the elimination of hepatitis B virus transmission in Micronesia \nand American Samoa. Pac Hth Dialog. 1996;3(2):140 -6. \n36. Andre FE . Summary of safety and efficacy data on a yeast -derived hepatitis B \nvaccine. Am J Med. 1989;87(3A):14S -20S.  \n37. Assad S, Francis A . Over a decade of experience with a yeast recombinant hepatitis \nB vaccine. Vaccine. 1999;18(1 -2):57-67. \n38. Patel DM, Butler J, Feldman S, Graves GR, Rhodes PG . Immunogenicity of hepatitis \nB vaccine in healthy very low birth weight infants. J Pediatr. 1997;131(4):641 -3. \n39. Bruce MG, Bruden D, Hurlburt D, Morris J, Bressler S, Thompson G, et al.  Protection \nand antibody levels 35 years after primary series with hepatitis B vaccine and \nresponse to a booster dose. Hepatology. 2022;76(4):1180 -9. \n40. Bruce MG, Bruden D, Hurlburt D, Zanis C, Thompson G, Rea L, et al.  Antibody Levels \nand Protection After Hepatitis B Vaccine: Results of a 30 -Year Follow -up Study and \nResponse to a Booster Dose. J Infect Dis. 2016;214(1):16 -22. \n41. CDC. Impact of the 1999 AAP/USPHS Joint Statement on Thimerosal in Vaccines on \nInfant Hepatitis B Vaccination Practices. MMWR Morb Mortal Wkly Rep. \n2001;50(6):94 -7. \n42. Kolasa MS, Tsai Y, Xu J, Fenlon N, Schillie S . Hepatitis B Surface Antigen Testing \nAmong Pregnant Women, United States 2014. Pediatr Infect Dis J. 2017;36(7):e175 -\ne80.  \n43. Koneru A, Fenlon N, Schillie S, Williams C, Weng MK, Nelson N . National Perinatal \nHepatitis B Prevention Program: 2009 -2017. Pediatrics. 2021;147(3).  \n44. Nolt D, O'Leary ST, Aucott SW . Risks of Infectious Diseases in Newborns Exposed to \nAlternative Perinatal Practices. Pediatrics. 2022;149(2).  \n45. Pham TTH, Maria N, Cheng V, Nguyen B, Toy M, Hutton D, et al.  Gaps in Prenatal \nHepatitis B Screening and Management of HBsAg Positive Pregnant Persons in the \nU.S., 2015 -2020. Am J Prev Med. 2023;65(1):52 -9. \n17 \n 46. Willis BC, Wortley P, Wang SA, Jacques -Carroll L, Zhang F . Gaps in hospital policies \nand practices to prevent perinatal transmission of hepatitis B virus. Pediatrics. \n2010;125(4):704 -11. \n47. Martin JA, Osterman MJK . Changes in Prenatal Care Utilization:United States, 2019 -\n2021. Natl Vital Stat Rep. 2023;72(4):1 -14. \n48. Yusuf HR, Daniels D, Smith P, Coronado V, Rodewald L . Association between \nadministration of hepatitis B vaccine at birth and completion of the hepatitis B and \n4:3:1:3 vaccine series. JAMA. 2000;284(8):978 -83. \n49. Mennito SH, Darden PM . Impact of practice policies on pediatric immunization \nrates. J Pediatr. 2010;156(4):618 -22. \n50. CDC. 2025 Viral Hepatitis National Progress Report accessed 8/26/2025. \nhttps://www.cdc.gov/hepatitis/php/npr -2025/overview.html : CDC; 2025.  \n51. Sterne JAC, Savovic J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al.  RoB 2: a \nrevised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898.  \n52. Hopewell S, Chan AW, Collins GS, Hrobjartsson A, Moher D, Schulz KF, et al.  \nCONSORT 2025 Statement: Updated Guideline for Reporting Randomized Trials. \nJAMA. 2025;333(22):1998 -2005.", "summary": "1   ACIP Meeting Materials for Public Posting:  Hepatitis B Birth Dose Briefing Document     Contents   1. Background   2. Epidemiology   3. Systematic Review s for studies  on hepatitis B birth dose vaccine   4. Appendices   Appendix 1 ACIP Recommendations   Appendix 2 Global Recommendations     1. Background     Introduction   Hepatitis B virus (HBV) infection can be transmitted from mother -to-child during pregnancy and delivery.  Without any interventions, up to 85% of infants born to…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-september-18-19-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-09-18-19/hep-b-birth-dose-briefing-508.pdf", "doc_date": "2025-09-18", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 17}
{"title": "hep b at birth vax safety summary 508", "content": "Disclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not \nbe construed to represent any agency determination or policy .  Page 1 of 84 \n ACIP BRIEFING MATERIALS FOR PUBLIC POSTING  \nThe Safety of Hepatitis B Vaccines  administered within 24 hrs of birth and within 30 days of \nbirth: A Rapid Systematic Review  \nTable of Contents  \nTable of Tables  ................................ ................................ ................................ ................................ ................................ .... 2 \nTable of Figures  ................................ ................................ ................................ ................................ ................................ ... 3 \nA. Methods  ................................ ................................ ................................ ................................ ................................ ..............  4 \nA.1. Key Question Development  ................................ ................................ ................................ ................................ .........  4 \nA.2. Literature Search  ................................ ................................ ................................ ................................ .........................  4 \nA.3. Study Selection  ................................ ................................ ................................ ................................ ............................  4 \nA.4. Data Extraction, Study Assessment, and Synthesis  ................................ ................................ ................................ ..... 7 \nA.5. GRADE -ing and Recommendation Development  ................................ ................................ ................................ ........  7 \nB. Summary of Evidence  ................................ ................................ ................................ ................................ .........................  8 \nB.1. GRADE -ed Summary of Findings for Hepatitis B vaccine administered in the first 24 hours of life  ............................  8 \nB.2. GRADE -ed Summary of Findings for Hepatitis B vaccine administered in the first 30 days of life  ............................  15 \nC. Extracted Evidence from Included Studies  ................................ ................................ ................................ .......................  42 \nC.1. Study Characteristics for All Included Studies  ................................ ................................ ................................ ...........  42 \nC.2. Outcomes for All Included Studies  ................................ ................................ ................................ .............................  44 \nC.3. Risk of Bias Assessments for All Included Studies  ................................ ................................ ................................ ..... 75 \nD. Search Strategies  ................................ ................................ ................................ ................................ ..............................  80 \nE. References  ................................ ................................ ................................ ................................ ................................ .........  83 \n \n \n \n  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not \nbe construed to represent any agency determination or policy .  Page 2 of 84 \n Table of Tables  \nTable 1. PI/ECO(ST) Criteria for Key Question  ................................ ................................ ................................ .......................  4 \nTable 2. GRADE Table: Allergic Reaction or Atopy Outcomes and the Administration of the Hepatitis B Vaccine in the \nfirst 24 hours of life  ................................ ................................ ................................ ................................ ................................  8 \nTable 3. GRADE Table: All -cause Mortality Outcomes and the Administration of the Hepatitis B Vaccine in the first 24 \nhours of life  ................................ ................................ ................................ ................................ ................................ .............  8 \nTable 4. GRADE Table: Infection or Infection -related Outcomes and the Administration of the Hepatitis B Vaccine in \nthe first 24 hours of life  ................................ ................................ ................................ ................................ ..........................  9 \nTable 5. GRADE Table: Local Injection Site Reaction Outcomes and the Administration of the Hepatitis B Vaccine in the \nfirst 24 hours of life  ................................ ................................ ................................ ................................ ................................  9 \nTable 6. GRADE Table: Systemic Reaction Outcomes and the Administration of the Hepatitis B Vaccine in the first 24 \nhours of life  ................................ ................................ ................................ ................................ ................................ ...........  11 \nTable 7. GRADE Table: Cardiopulmonary Outcomes and the Administration of the Hepatitis B Vaccine in the first 24 \nhours of life  ................................ ................................ ................................ ................................ ................................ ...........  13 \nTable 8. GRADE Table: Neurological Outcomes and the Administration of the Hepatitis B Vaccine in the first 24 hours \nof life  ................................ ................................ ................................ ................................ ................................ .....................  14 \nTable 9. GRADE Table: Adverse event following immunization (AEFI) outcomes and administration of the Hepatitis B \nVaccine in the first 30 days of life  ................................ ................................ ................................ ................................ ........  15 \nTable 10. GRADE Table: Allergic reaction and atopy outcomes and administration of the Hepatitis B Vaccine in the first \n30 days of life ................................ ................................ ................................ ................................ ................................ ........  16 \nTable 11. GRADE Table: Mortality outcomes and administration of the Hepatitis B Vaccine in the first 30 days of life  17 \nTable 12. GRADE Table: Infection outcomes and administration of the Hepatitis B Vaccine in the first 30 days of life  . 18 \nTable 13. GRADE Table: Local injection site outcomes and administration of the Hepatitis B Vaccine in the first 30 days \nof life  ................................ ................................ ................................ ................................ ................................ .....................  20 \nTable 14. GRADE Table: Neurodevelopmental outcomes and administration of the Hepatitis B Vaccine in the first 30 \ndays of life  ................................ ................................ ................................ ................................ ................................ ............  23 \nTable 15. GRADE Table: Neurologic outcomes and administration of the Hepatitis B Vaccine in the first 30 days of life\n ................................ ................................ ................................ ................................ ................................ ..............................  28 \nTable 16. GRADE Table: Cardiopulmonary outcomes and administration of the Hepatitis B Vaccine in the first 30 days \nof life  ................................ ................................ ................................ ................................ ................................ .....................  30 \nTable 17. GRADE Table: Systemic reactions and administration of the Hepatitis B Vaccine in the first 30 days of life  .. 31 \nTable 18. GRADE Table: Other outcomes and administration of the Hepatitis B Vaccine in the first 30 days of life  ...... 40 \nTable 19. Characteristics of Studies Meeting Inclusion Criteria  ................................ ................................ .........................  42 \nTable 20 . Adverse Events Following Immunization (AEFI)  Results of Studies Meeting Inclusion Criteria  ........................  44 \nTable 21. Allergic Reaction and Atopy Results of Studies Meeting Inclusion Criteria  ................................ .......................  44 \nTable 22. All Death Outcomes Results of Studies Meeting Inclusion Criteria  ................................ ................................ .... 45 \nTable 23. Infection Results of Studies Meeting Inclusion Criteria  ................................ ................................ ......................  47 \nTable 24. Local Injection -site Outcomes Results of Studies Meeting Inclusion Criteria  ................................ ....................  48 \nTable 25. Neurodevelopmental Results of Studies Meeting Inclusion Criteria  ................................ ................................ . 52 \nTable 26. Neurologic Results of Studies Meeting Inclusion Criteria  ................................ ................................ ...................  60 \nTable 27. Cardiopulmonary Results of Studies Meeting Inclusion Criteria  ................................ ................................ ........  61 \nTable 28. Systemic Reactions Results of Studies Meeting Inclusion Criteria  ................................ ................................ ..... 63 \nTable 29. Other Reactions Results of Studies Meeting Inclusion Criteria  ................................ ................................ ..........  74 \nTable 30. Search Strategies and Results  ................................ ................................ ................................ ..............................  80 \n \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not \nbe construed to represent any agency determination or policy .  Page 3 of 84 \n Table of Figures  \nFigure 1. Results of the Study Selection Process  ................................ ................................ ................................ ..................  6 \nFigure 2. Risk of Bias Assessments for Randomized Controlled Trials  ................................ ................................ ...............  75 \nFigure 3. Risk of Bias Assessments for Cohort Studies  ................................ ................................ ................................ ........  77 \nFigure 4. Risk of Bias Assessments for Case Control Studies  ................................ ................................ ..............................  78 \nFigure 5. Risk of Bias Assessments for Case Series Studies  ................................ ................................ ................................  79 \n \n  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not \nbe construed to represent any agency determination or policy .  Page 4 of 84 \n A. Methods  \nA.1. Key Question Development  \nThe Key Question s were  developed  by infectious disease and systematic review methodology subject matter experts  \nusing the PICO  framework1 (Population, Intervention, Comparator, and Outcome ). The Key Question  and PI /ECO(ST) \nCriteria  used to guide the literature review are below and in Table 1.   \n1. What is the safety of the hepatitis B vaccine administered within the first 24 hours  of life ? \n2. What is the safety of the hepatitis B vaccine administered within the first 30 days of life?  \nTable 1. PI/ECO(ST) Criteria for Key Question  \nPI/ECO(ST) ELEMENT  Description for this Review  \nPopulation  Neonates, Newborns, Infants   \nIntervention or \nExposure  Hepatitis B vaccine administration  within the first 30 days  of birth  \n• HepB, HepB -BD, HBV, Engerix -B, Recombivax HB  \n• Administration in the f irst 24 hours of life:  \no Studies clearly identify vaccination within  \n▪ the first 24 hours of life or birth,  \n▪ the first day of life, or  \n▪ the day of or the day after birth  \n• Administration  in the first 30 days of life :  \no Studies clearly identify vaccination  \n▪ in first 30 days of life , \n▪ at <0.1 years of age,  or \n▪ of Neonate (aged 28 days or less)  \nComparator (if \napplicable)  Any or none  \nOutcome(s)  Adverse events  \nAdverse outcomes  \nSafety outcomes  \nSide effects  \nReaction  \nAdverse reaction  \nAdverse effect  \nSerious adverse event  \nSetting  Any \nTime Frame  Any publication years  \nAny duration of follow up  \n \nA.2. Literature Search  \nA CDC informationist (J.T.)  developed search strategies from the Key Question  and PICO criteria,  and performed the \nsearch in MEDLINE, EMBASE , CINAHL , and Cochrane Library  from  the start of each database to July 31, 2025 . Search \nstrategies and results are provided in  Section D of this document ( Search Strategies ).  \nA.3. Study Selection  \nResults of the literature searches were uploaded into EndNote 21 (Clarivate Analytics©, Thomson Reuters, New \nYork, NY, USA), duplicate records were removed, and unique t itles and abstracts  were uploaded to Covidence \n(Veritas Health Innovation Ltd., Melbourne, VIC, Australia) where a second round of deduplication was conducted. \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not \nbe construed to represent any agency determination or policy .  Page 5 of 84 \n Two reviewers (AH, LZ, MM1, MM2, RG, TM ) independently screened all titles and abstracts and removed irrelevant \nreferences. Relevant  full texts  were screened independent ly by two  reviewers  (AH, LZ, MM1, MM2, RG, TM ) and \ndisagreements were resolved by consensus . All studies were screened according to the pre -identified exclusion \ncriteria below, and results of the study selection process are provided in Figure 1 . \n \nCriteria for excluding studies from the literature review include:  \n1. No full text  available;   \n2. Not available in English;  \n3. Not relevant to key question ; \n4. No p opulation of interest  (e.g., no neonates) ; \n5. No intervention  of interest  (e.g., no hepatitis b vaccine) ; \n6. No outcome of interest  (e.g., no adverse event outcomes) ; \n7. No primary data  or secondary data not systematically collected  (no reproducible methods) ; \n8. Data collected prior to licensure ; or \n9. Insufficient methodologic reporting ( i.e., poster, abstract, letter to editor ) \n \n  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not \nbe construed to represent any agency determination or policy .  Page 6 of 84 \n \n  \n   Figure 1. Results of the Study Selection Process   \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nIdentification  \nStudies screened (n = 1907) \nStudies sought for retrieval (n = 229) \nStudies assessed for eligibility (n = 229)     References removed (n = 9)   \nDuplicates identified manually (n = 9) \nDuplicates identified by Covidence (n = 0)  \nMarked as ineligible by automation tools (n =  0) \nOther reasons (n = 0) \nStudies excluded (n = 1678) \nStudies not retrieved (n = 0) \nStudies excluded (n = 158)   \nNo intervention  of interest  (n = 48) \nNo outcome of interest  (n = 30) \nNot relevant to key question  (n = 7) \nNo population of interest  (n = 51) \nNot available in English  (n = 5) \nInsufficient methodologic reporting (i.e., poster, abstract, \nletter to editor)  (n = 8) \nNo primary data collection  or secondary data not \nsystematically collected (n = 8)  \nIncluded  Studies assessed for administration of HepB birth \ndose alone and HepB vaccine specific outcomes \n(n = 71)     \nScreening  Studies from databases/registers (n = 1916 ) \nMEDLINE  (n = 1916 ) \nStudies excluded  (n = 51) \nOutcome or population not stratified  by HepB birth dose or \nHepB vaccine outcome  (n = 47)  \nSystematic reviews/meta -analyses (n = 4)  \nStudies extracted  for HepB birth dose (n = 20)  \nReported HepB birth dose within 24 hours of birth  (n = 5) \n   \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 7 of 84 \n A.4. Data Extraction , Study Assessment , and Synthesis  \nData from studies meeting inclusion criteria were independently extracted by two reviewers using a standardized Microsoft Excel (2021) form, and \ndifferences were reconciled by discussion. Extracted data included study characteristics, population characteristics (e.g., case and control definitions), \noutcome definitions, an d results (presented in Section C ). Outcome data were extracted as presented in the studies or calculated using data provided. For \nthe purposes of this review, statistical significance was defined as p ≤ 0.05 . The r isk of bias for each study was assessed according to study type  using \nstandardized  risk of bias tools  appropriate to the identified study type. Tools were modified to specify  birthweight, age at administration, prematurity, and \nmaternal hepatitis b status as  confounding factors  and to include an assessment of conflict -of-interest  disclosures . The Newcastle -Ottawa Scale was used for \ncohort and case control studies , R.O.B2. for randomized controlled trials (RCTs) , and JBI tools were used to assess the risk of  bias for Case Series and \nSystematic Reviews2-4. The signaling questions used to assess study conduct and risk of bias and results are presented in Section C.3 . The evidence was \nnarratively synthesized for  each  outcome domain, and for specific outcomes where definitions aligned.  \nA.5. GRADE -ing and Recommendation Development  \nThe Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach  was used to assess the  risk of bias , imprecision, \ninconsistency, and indirectness , and final confidence for the body of evidence  foreach outcome  using .5 The Summary of findings and confidence in the \nevidence are found in Section B . \n  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 8 of 84 \n B. Summary of Evidence  \nB.1. GRADE -ed Summary of Findings  for Hepatitis B vaccine administered in the first 24 hours of life  \nKey Question: Among children, what is the safety of the hepatitis B vaccine administered in the first 24 hours  of life?  \n Table 2. GRADE Table: Allergic Reaction or Atopy Outcomes and the Administration of the Hepatitis B Vaccine in the first 24 hours of l ife \nOutcome  Summary  Studies  Risk of \nBias  Imprecision  Inconsistency  Indirectness  Confidence  \nSummary Events  The evidence from one cohort study suggests there is no \ndifference in the risk of an allergic reaction and the receipt \nhepatitis B vaccination in the first 24 hours of life.  1 Cohort6 \n(N = 5,655)  No \nconcerns No concerns No concerns  No concerns  Low \nconfidence  \nAllergic reaction  One cohort6 of normal birthweight, full term, U.S. infants in \nthe VSD (NCK) reported no difference in the risk of an allergic \nreaction among infants with a record of Hepatitis B \nvaccination on the first day of life or the day after compared \nwith infants with no record of Hepatitis B vaccination  within \nthe first 21 days of life . [RR: 0.87; (95%CI: 0.05 -13.8); p=0.99; \n1/2,718 vs 1/2,353].  1 Cohort6 \n(N = 5,655)  No \nconcerns  No concerns  No concerns  No concerns  Low \nconfidence  \n \nTable 3. GRADE Table: All -cause Mortality  Outcomes and the Administration of the Hepatitis B Vaccine in the first 24 hours of life  \nOutcome  Summary  Studies  Risk of \nBias  Imprecision  Inconsistency  Indirectness  Confidence  \nSummary Events  The evidence from one Cohort7 suggest s no difference in the \nrisk of all-cause mortality among those who did and did not \nand receive a hepatitis B vaccination in the first 24 hours of \nlife. 1 Cohort7 \n(N = 818)  No \nconcerns No concerns No concerns  No concerns  Low \nconfidence  \nAll-cause mortality  One cohort7 of extremely preterm infants (<29 wks gestation) \nin Australia’s Surveillance of Adverse Events Following \nImmunization in the Community suggested there is no \ndifference in risk of death during the first 3 months of life \nwhen comparing infants with a record of receiving Hepatitis B \nvaccine within 24 hours of birth to infants with no record in \nthe first 24  hours  [aRR: 1.13; (95%CI: 0.42 -2.81); 7/306 vs \n14/512].  1 Cohort7 \n(N = 818)  No \nconcerns  No concerns  No concerns  No concerns  Low \nconfidence  \n \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 9 of 84 \n Table 4. GRADE Table: Infectio n or Infection -related  Outcomes and the Administration of the Hepatitis B Vaccine in the first 24 hours of life  \nOutcome  Summary  Studies  Risk of \nBias  Imprecision  Inconsistency  Indirectness  Confidence  \nInfections  The evidence from one cohort study suggests there is a reduction \nin the risk of an invasive diagnostic procedure including blood and \nCSF cultures , and a reduction in positive cultures , among infants \nwho recei ved a hepatitis B vaccination in the first 24 hours of life , \ncompared to those who did not . 1 Cohort6 \n(N = 5,655)  \n No \nconcerns No concerns No concerns  No concerns  Low \nconfidence  \nBlood or CSF culture \nperformed  One cohort6 of normal birthweight, full term U.S. infants in the  VSD \n(NCK) reported  a reduction in the age -stratified risk of having a \nblood or CSF culture performed in the first three weeks of life when \ncomparing infants with a record of receiving thimerosal -containing \nHepatitis B vaccine on the day of birth or the day after compared to  \ninfants with no record of Hepatitis B vaccination [RR: 0.71; (95%CI: \n0.63 -0.80); p <0.001; 126/2,718 vs 203/2,353].  1 Cohort6 \n(N = 5,655)  No \nconcerns  No concerns  No concerns  No concerns  Low \nConfidence  \nBlood or CSF culture \npositive  One cohor t6 of normal birthweight, full term U.S. infants in the VSD \n(NCK) reported  a reduction in the age -stratified risk of having a \npositive blood or CSF culture in the first three weeks of life when \ncomparing infants with a record of receiving thimerosal -containing \nHepatitis B vaccine on the day of birth or the day after compared to  \ninfants with no record of Hepatitis B vaccination [RR: 0.57; (95%CI: \n0.35 -0.94); p <0.027; 7/2,718 vs 16/2,353].  1 Cohort6 \n(N = 5,655)  No \nconcerns  No concerns  No concerns  No concerns  Low \nConfidence  \n \nTable 5. GRADE Table: Local Injection Site Reaction  Outcomes and the Administration of the Hepatitis B Vaccine in the first 24 hours of life  \nOutcome  Summary  Studies  Risk of \nBias  Imprecision  Inconsistency  Indirectness  Confidence  \nLocal Injection Site \nReactions  Two RCTs suggest no difference in local side effects, pain or \nsoreness, redness, or swelling at the injection site within 1 \nweek of vaccination or less when comparing infants who \nreceived a dose of a Hepatitis B Vaccine within the first 24 \nhours, compared to those who were vaccinated never or \nlater.  2 RCT8,9 \n(N = 741) \n Serious \nconcernsa No concerns No concerns  No concerns  Low \nconfidence  \nLocal side effects  One RCT of Egyptian infants8, compared the outcome of local \nside effects (e.g., local soreness, or temporary \nredness/induration at the injection site) 1 week after \nvaccination among infants randomized to administration of \nthe first of dose of Recombivax immediately after delivery, at 1 RCT8 \n(N = 536) \n Serious \nconcernsa No concerns  No concerns  No concerns  Low \nconfidence  \n \na Inadequate randomization, unclear allocation concealment and blinding  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 10 of 84 \n Outcome  Summary  Studies  Risk of \nBias  Imprecision  Inconsistency  Indirectness  Confidence  \ntwo months of age, or at 18 months of age, and reported a \nhigher proportion of local side effects among those who \nreceived the vaccine at birth  (2.8% (5/178) at birth, vs  7.2% \n(12/167), vs. 1.6% (3/191) at 18 months]. No relationship was \nfound between side effects and weight or prematurity.  \nPain  In a RCT of Israeli infants9, 4/52 (7.7%) infants who received \nEngerix -B within 24 hours of birth and 4/153 (2.6%) who \nreceived BioHepB within 24 hours of birth experienced pain \nwith movement within 5 days of vaccination. Additionally, \n4/52 (7.7%) infants who received Engerix -B withi n 24 hours of \nbirth and 2/153 (1.3%) who received BioHepB within 24 hours \nof birth experienced pain with pressure within 5 days of \nvaccination.  The HepB vaccine BioHepB is not approved for \nuse in the United States.  1 RCT9 \n(N = 205)  Serious  \nconcernsb Some \nconcernsc No concerns  No concerns  Very low \nconfidence  \n \nRedness or erythema  One RCT of Israeli infants9 reported no redness or erythema \nwithin 5 days of vaccination among infants randomized to \nreceipt of Engerix -B or BioHepB within 24 hours of birth (0/52 \nvs. 0/153). The HepB vaccine BioHepB is not approved for use \nin the United States.  1 RCT9 \n(N = 205)  \n  \n Serious  \nconcernsd \n \n \n Some \nconcernsd \n \n \n No concerns  \n \n \n No concerns  \n \n \n Very low \nconfidence  \n \n \n \nSwelling  One randomized control trial of Israeli infants9 reported a \nhigher proportion of swelling at the injection site within five \ndays of vaccination among infants who received thimerosal -\ncontaining Engerix -B within 24 hours of birth compared with \nthose who received BioHepB within 24 hours of birth [4/52 \n(7.7%) vs. 3/153 (2.0%)]  The HepB vaccine BioHepB is not \napproved for use in the United States.  1 RCT9 \n(N = 205)  \n Serious  \nconcernse \n Some \nconcernsd \n No concerns  \n \n No concerns  \n  \n \n Very low \nconfidence  \n \n \n \nb Unclear allocation concealment; absence of statistical analyses and reporting on protocol deviations  \nc Small sample size  \nd Unclear allocation concealment; absence of statistical analyses and reporting on protocol deviations  \ne Unclear allocation concealment; absence of statistical analyses and reporting on protocol deviations  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 11 of 84 \n Table 6. GRADE Table: Systemic Reaction  Outcomes and the Administration of the Hepatitis B Vaccine in the first 24 hours of life  \nOutcome  Summary  Studies  Risk of \nBias  Imprecision  Inconsistency  Indirectness  Confidence  \nSystemic Reactions  2 RCTs and 2 cohorts suggested no difference in fever \nwhen comparing infants who were vaccinated in the first \n24h with a Hep B Vaccine to those who were vaccinated \nlater , not at all , or with a different vaccine.  \n \nOne RCT9 of Israeli infants suggested no difference in  \nanorexia/ decreased appetite, diarrhea or vomiting, \nhowever, it did suggest an increase in  irritability or \nfussiness  when comparing  infants who received hepatitis \nB vaccine in the first 24 hours after birth with infants who \nreceived the BioHepB (not approved in U.S.) vaccine in \nthe first 24 hours.  2 RCTs8,9 \n(N = 741)  \n \n2 cohort6,10 \n(N = 16,484)  Serious \nconcernsf \n \nSome \nconcernsg \n \n Some \nconcernsh \n \n \nNo concerns  \n \n No concerns  \n \n \nNo concerns  \n \n \n \n \n No concerns  \n \n \nNo concerns  \n \n \n \n \n Very low \nconfidence  \n \n \nVery low \nconfidence  \nAnorexia/Decreased \nappetite  In a RCT of Israeli infants9, 0/52 infants who received \nEngerix -B within 24 hours of birth and 3/153 (2.0%) who \nreceived BioHepB within 24 hours of birth experienced \nanorexia within 5 days of vaccination.  The HepB vaccine \nBioHepB is not approved for use in the United States.  1 RCT9 \n(N = 205)  Serious \nconcernsi Some concernsj No concer ns No concer ns Very low \nconfidence  \n Diarrhea  or vomiting  In a RCT of Israeli infants9, 0/52 infants who received \nEngerix -B within 24 hours of birth and 1/153 (0.64%) who \nreceived BioHepB within 24 hours of birth experienced \ndiarrhea or vomiting within 5 days of vaccination. The \nHepB vaccine BioHepB is not approved for use in the \nUnited State s. 1 RCT 9 \n(N = 205)  Serious \nconcernsk Some concernsl \n No concerns  No concerns  Very low \nconfidence  \nFever  Two RCTs  reported no difference in fever among infants \nwho received Hepatitis B vaccination within 24 hours of \nbirth whether compared to the same vaccine at 2 months \nand at 18 months of age, or a combination vaccine \ndelivered at birth.   \n \n \n \n  \n \n \n \n  \n \n \n \n  \n \n \n \n  \n \n \n \n  \n \n \nVery low  \nconfidence  \n \nf Inadequate randomization, unclear allocation concealment and blinding; absence of statistical analyses and reporting on proto col deviations  \ng One study compared groups with different birth years , and did not adjust or age stratify the results.  \nh One study had a small sample size in one group.  \ni Unclear allocation concealment; absence of statistical analyses and reporting on protocol deviations  \nj Small sample size  \nk Unclear allocation concealment; absence of statistical analyses and reporting on protocol deviations  \nl One study had a small sample size in one group.  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 12 of 84 \n Outcome  Summary  Studies  Risk of \nBias  Imprecision  Inconsistency  Indirectness  Confidence  \n• One RCT of Egyptian infants8, compared the \noutcome of local side effects 1 week after \nvaccination among infants randomized to \nadministration of the first of dose of Recombivax \nimmediately after delivery (n=178), or at 18 months \nof age (n=191). There was no difference in the \nproportion who experienced fever among those \nwho received the vaccine immediately after delivery \n(5.6%) compared to  at 2 months (7.2%) or  at 18 \nmonths (2.1%).  \n• In a RCT of Israeli infants9, 0/52 infants who received \nEngerix -B within 24 hours of birth and 2/153 (1.3%) \nwho received BioHepB within 24 hours of birth \nexperienced a temperature ≥38 ⁰C within 5 days of \nvaccination. The HepB vaccine BioHepB is not \napproved for use in the United States.  \n \nTwo cohorts reported inconsistent results on the \nproportion fever among  infants who did and did not \nreceive a dose of Hepatitis B vaccine in the first day of life , \nwith the stronger study reporting no difference  when \nadjusting for age at birth and year of vaccination ; however,  \nthe study that compared different birth years and did not \nadjust or age -stratify the results  report ed a higher \nproportion of fever among those who received the Hep B \nvaccine in the first day of life . \n• One cohort6 of normal birthweight, full term, U.S. \ninfants in the Vaccine Safety Datalink (NCK) reported \nno difference in the risk of a fever in the first three \nweeks of life when comparing infants with a record \nof receiving thimerosal -containing Hepatitis B \nvaccine on the day of birth or day after birth with \ninfants with no record of Hepatitis B vaccination \nwithin the first 21 days of life [RR: 0.85; (95%CI: 0. 6-\n1.1); p=0. 28; 21/2,718 vs 25/2,353].  \n• In a cohort study of full -term Israeli infants10, \n68/5,819 (1.2%) full -term infants receiving hepatitis  \n2 RCTs8,9 \n(N = 741) \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n2 cohort6,10 \n(N = 16,484 ) \n \n \n \n \n \n \n \n \n \n  \nSerious  \nconcernsm \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nSome \nconcernsn \n \n \n \n \n \n \n \n \n \n Some  concernso \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nNo concerns  \n \n  \nNo concerns  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nNo concerns  \n \n \n \n \n  \nNo concerns  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nNo concerns  \n \n \n \n \n  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nVery low \nconfidence  \n \nm Inadequate randomization, unclear allocation concealment and blinding; absence of statistical analyses and reporting on proto col deviations  \nn One study compared groups with different birth years and did not adjust , or age stratify the results.  \no One study had a small sample size  in one group.  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 13 of 84 \n Outcome  Summary  Studies  Risk of \nBias  Imprecision  Inconsistency  Indirectness  Confidence  \nB vaccination and 27/5,010 (0.54%) full -term infants \nnot receiving hepatitis B vaccine had a birth \nhospitalization discharge diagnosis of “neonatal \nfever” above 37. 5⁰C (p<0.001). Fevers above 38⁰C \nwere noted in 50 (0.9%) of vaccinated infants and 27 \n(0.54%) of unvaccinated infants (p<0.05). \nIdentifiable causes of fever (e.g ., sepsis, \ndehydration, maternal fever, respiratory distress) \nwere noted among 15 vaccinated inf ants (0.3%) and \n13 unvaccinated infants (0.3%). Unexplained fevers \nwere noted among 35 (0.6%) vaccinated infants and \n14 (0.3%) unvaccinated infants (p=0.013).  \n Irritability or fussiness  In a RCT of Israeli infants9, 6/52 (11.5%) infants who \nreceived Engerix -B within 24 hours of birth and 5/153 \n(3.3%) who received BioHepB within 24 hours of birth \nexperienced irritability within 5 days of vaccination. The \nHepB vaccine BioHepB is not approved for use in the \nUnited States  1 RCT9 \n(N = 205)  Serious  \nconcernsp Some concernsq No concerns  No concerns  Very low \nconfidence  \n \nTable 7. GRADE Table: Cardiopulmonary  Outcomes and the Administration of the Hepatitis B Vaccine in the first 24 hours of life  \nOutcome  Summary  Studies  Risk of \nBias  Imprecision  Inconsistency  Indirectness  Confidence  \nCardiopulmonary  The evidence from one cohort study of extremely preterm \ninfants suggests a reduction in the adjusted risk of \nbronchopulmonary dysplasia among infants with a record of \nreceiving Hepatitis B  vaccine in the first 24 hours of life \ncompared to infants with no record in the first 24h  1 Cohort7 \n(N = 818)  No \nconcerns No concerns No concerns  No concerns  Low \nconfidence  \nBronchopulmonary \ndysplasia  One cohort7 of extremely preterm infants (<29 wks gestation) \nin Australia’s Surveillance of Adverse Events Following \nImmunization in the Community suggested there is a \nreduction in risk of bronchopulmonary dysplasia when \ncomparing infants with a record of receiving Hepatitis B \nvaccine within 24 hours of birth to infants with no record \nwhen adjusting for maternal age, maternal smoking, Apgar 1 Cohort7 \n(N = 818)  No \nconcerns  No concerns  No concerns  No concerns  Low \nconfidence  \n \np Unclear allocation concealment; absence of statistical analyses and reporting on protocol deviations  \nq Small sample size  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 14 of 84 \n score and congenital heart disease status [aRR: 0.83; (95%CI: \n0.68 -1.0); 155/306 vs 317/512].  \n \nTable 8. GRADE Table: Neurological  Outcomes and the Administration of the Hepatitis B Vaccine in the first 24 hours of lif e \nOutcome  Summary  Studies  Risk of \nBias  Imprecision  Inconsistency  Indirectness  Confidence  \nNeurological  The evidence from one cohort of normal birthweight, full \nterm infants in the U.S.VSD suggested there is no difference \nin the risk of seizures or Neurologic disease other than \nseizures  when comparing infants who received Hepatitis B \nvaccine on the day of birth or the day after birth to infants \nwith no record of vaccination in the first 24 hours of life . 1 Cohort6 \n(N = 5,655)  \n  No \nconcerns No concerns No concerns  No concerns  Low  \nconfidence  \nSeizure  One cohort6 of normal birthweight, full term U.S. infants in \nthe VSD (NCK) suggested there is no difference in the risk of \nseizures in the first three weeks of life when comparing \ninfants with a record of receiving thimerosal -containing \nHepatitis B vaccine on the day  of birth or day after birth with \ninfants with no record of Hepatitis B vaccination within the \nfirst 21 days of life [RR: 0.22; (95%CI: 0.02 -1.9); p=0.19; \n1/2,718 vs 4/2,353].  1 Cohort6 \n(N = 5,655)  \n  No \nconcerns  No concerns  No concerns  No concerns  Low \nconfidence  \nNeurologic disease, other \nthan seizure  One cohort6 of normal birthweight, full term U.S. infants in \nthe VSD (NCK) suggested there is no difference in the risk of \nneurologic disease in the first three weeks of life when \ncomparing infants with a record of receiving thimerosal -\ncontaining Hepatitis B vaccine on the day of birth or day after \nbirth with infants with no record of Hepatitis B vaccination \nwithin the first 21 days of life [RR: 1.7; (95%CI: 0.3 -9.4); \np=0.69; 4/2,718 vs 2/2,353].  1 Cohort6 \n(N = 5,655)  \n No \nconcerns  No concerns  No concerns  No concerns  Low \nconfidence  \n \n  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 15 of 84 \n B.2. GRADE -ed Summary of Findings for Hepatitis B vaccine administered in the first 30 days of life  \nKey Question: Among children, what is the safety of the hepatitis B vaccine administered in the first 30 days  of life?  \n \nTable 9. GRADE Table: Adverse event following immunization (AEFI)  outcomes and administration  of the Hepatitis B Vaccine in the first 30 days of life  \nOutcome  Summary  Studies  Risk of \nBias Imprecision  Inconsistency  Indirectness  Confidence  \nAll Adverse events \nfollowing immunization \n(AEFI)  The evidence from two single group studies suggest ing that \nserious adverse events can occur  following the administration \nof a thimerosal -containing Hepatitis  B vaccine in the first 30 \ndays of life  in neonates in Columbia and the U.S. The three \nserious adverse events in the U.S. occurred in the context of \nthe administration of 12 million doses among infants less than \n1 year of age . 2 DES11,12  \n(N = 177) \n Some \nconcernsr \n Some \nconcernss No concerns  No concerns  Very low \nconfidence  \nCerebral venous \nthrombosis/intraventricular \nhemorrhage  \n One case series examined  VAERS reports of U.S. neonates <0.1 \nyears of age  who received a thimerosal -containing Hepatitis B \nvaccine between 1991 – 199412 and identified  one serious \nreport of c erebral venous thrombosis/intraventricular \nhemorrhage  [1.7% (1/60)] . 1 DES12 \n(N = 60) Some  \nconcernst No concerns  No concerns  No concerns  Very Low  \nconfidence  \nDisseminated intravascular \ncoagulation  One case series12 examined  VAERS reports  of U.S. neonates \n<0.1 years of age who received a thimerosal -containing \nHepatitis B vaccine between 1991 – 1994 and identified one \n(1.7%) serious report of d isseminated intravascular coagulation  \n[1.7% (1/60)] .  1 DES12  \n(N = 60)  Some \nconcernsa No concerns  No concerns  No concerns  Very Low \nconfidence  \nNecrotizing enterocolitis  One case series12 examined  VAERS reports of U.S. neonates \n<0.1 years of age who received a thimerosal -containing \nHepatitis B vaccine between 1991 – 1994 and identified one  \nserious report of necrotizing enterocolitis  [1.7% (1/60 )]. 1 DES12 (N \n= 60)  Some \nconcernsa No concerns  No concerns  No concerns  Very Low \nconfidence  \nSerious adverse events  A single group cohort11 of 117 healthy neonates  in Colombia \nwho received a n Engerix -B Hepatitis B vaccine dose  at birth , \nreported one adverse event (cough requiring hospitalization) \n37 days after vaccination deemed serious, but unrelated to \nvaccine by study investigators  [0.9% (1/117)].  1 DES11 \n(N = 117)  Some \nconcernsu Some \nconcernsv No concerns  No concerns  Very low \nconfidence  \n \nr Measurement bias: -1 for retrospective reporting and unclear temporality  \ns Small sample size  \nt Measurement bias: -1 for retrospective reporting  and unclear temporality  \nu Measurement & misclassification: -1 for unclear day of dosing; -1 for no comparator group  \nv Small sample size  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 16 of 84 \n  \nTable 10. GRADE Table: Allergic reaction and atopy outcomes and administration of the Hepatitis B Vaccine in the first 30 days of life  \nOutcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence  \nAll Allergic reactions \nand Atopy  One RCT13 and one Cohort6 suggest a low rate of occurrence \nof allergic reactions and atopy among infants vaccinated with \nHepatitis -B vaccines in the first 30 days of life, and no \ndifference in the occurrence or risk of allergic reactions and \natopy when comparing those who did rece ive the vaccine in \nthe first 30 days compared to those who did not receive the \nvaccine, or compared to those receiving a Hepatitis -B vaccine \nthat is not approved in the United States  (U.S.) . 1 RCT13 \n(N = 360)  \n \n1 Cohort6 \n(N = 5,655)  Some \nconcernsw No concerns  No concerns  No concerns  Moderate \nconfidence  \nAllergic reaction  One cohort6 of normal birthweight, full term , U.S.  infants in \nthe VSD (NCK) reported  no difference in the  risk of an allergic \nreaction in the first three weeks of life when comparing infants \nwith a record of receiving thimerosal -containing Hepatitis B \nvaccine in the first 21 days of life to infants with no record of \nHepatitis B vaccination during the same time  [RR: 0. 71 (95%CI: \n0.04-11.4 ); p=0.99 ; 1/3,302 vs 1/2,353]. This remained \nconsistent in a sub -analysis restricting the infants with a record \nof Hepatitis B vac cination on the day of birth or day after birth \nwith infants with no record of Hepatitis B vaccination  in the \nfirst 21 days of life  [RR: 0. 87; (95%CI: 0. 05-13.8 ); p=0.99 ; \n1/2,718 vs 1/2,353].  1 Cohort6  \n(N = 5,655)  Some \nconcerns1 No concerns  No concerns  No concerns  Low \nconfidence  \nEczema  One RCT of healthy infants in India13 reported no cases of \neczema in  infants vaccinated with Engerix -B in the first 2 \nweeks of life  or in infants vaccinated with HepB Gene Vac -B \nwithin first 2 weeks of life  (0/130 vs. 0/ 1320, p=NR ). The HepB \nGene Vac -B is not approved for use in the United States.  1 RCT13 (N = \n360)  No concerns  No concerns  No concerns  No concerns  High \nconfidence  \n \n \n \nw Measurement & misclassification: -1 for unclear duration of follow up.  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 17 of 84 \n Table 11. GRADE Table: Mortality outcomes and administration of the Hepatitis B Vaccine in the first 30 days of life   \nOutcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence  \nAll Death \nOutcomes  The evidence  from 1 RCT14 and 2 cohort studies7,15 suggests  \nno difference in the proportion of deaths among infants \nvaccinated with  any Hepatitis B Vaccine  at birth compared to \nthose who were not vaccinated at birth.  \n \nThe evidence from one cohort study15 suggests no difference \nin expected, or un expected deaths or deaths due to sudden \ninfant death syndrome (SIDS).   1 RCT14 \n(N = 280) \n \n2 Cohorts7,15 \n(N =1,086)  Some  concernsx No concerns  No concerns  No concerns  Low \nConfidence  \nAll-cause \nmortality  One RCT14 of unvaccinated, healthy infants in the U.S. reported \nno deaths (N=208) at 7 months follow up among infants who \nreceived  different timing of the first lifetime dose and the \nsubsequent series of any HBV Vaccine, specifically  DTaP-HepB  \nvaccine s at 2, 4 and 6 months of age, and infants who received \nHepB  vaccine at birth, 1 month and 6 months of age and DTaP \nat 2, 4 and 6  months of age.  \n \nOne cohort7 of extremely preterm infants (<29 wks gestation) \nin Australia’s Surveillance of Adverse Events Following \nImmunization in the Community suggested there is no \ndifference in risk of death during the first 3 months of life \nwhen comparing infants with a record  of receiving hepatitis b \nvaccine within 24 hours of birth to infants with no record in \nthe first 24 hours  [aRR: 1.13; (95%CI: 0.42 -2.81); 7/306 vs \n14/512].  \n \nThree case series  summarizing VAERS data16  for infants <1 \nmonth of age, reported 18 neonatal death reports were \nsubmitted between 2005 -201516 and 27 reports of death \nbetween 1991 -199812,17  \n• One case series16 of reports following single antigen \nthimerosal containing Hepatitis B vaccine in U.S. \ninfants aged <1 month in the VAERS between  2005 - \n2015 reported on Hepatitis B vaccine, 27/240 \n(11.3%) reports of death, including one due to sepsis.  \n• There were two case series  of VAERS reports in \nneonates following vaccination with a thimerosal -1 RCT14 \n(N = 265) \n \n \n \n \n \n \n1 Cohort7 \n(N = 818) \n \n \n \n \n \n \n \n3 DES12,16,17  \n(N = 2,011)  \n \n \n \n \n \n \n \n \n Some  concernse \n \n \n \n \n \n \nNo concerns  \n \n \n \n \n \n \n \n \nSome  concernsq  \n \n \n \n \n \n \n \n No concerns  \n \n \n \n \n \n \nNo concerns  \n \n \n \n \n \n \n \nNo concerns  \n \n \n \n \n \n \n \n \n \n \n \n No concerns  \n \n \n \n \n \n \nNo concerns  \n \n \n \n \n \n \n \nNo concerns  \n \n \n \n \n \n \n \n \n \n \n \n No concerns  \n \n \n \n \n \n \nNo concerns  \n \n \n \n \n \n \n \nNo concerns  \n \n \n \n \n \n \n \n \n \n \n \n Low \nconfidence  \n \n \n \n \n \nLow \nconfidence  \n \n \n \n \n \n \nLow \nconfidence  \n \n \n \n \n \n \n \n \n \n \n \n \nx Unanalyzed loss to follow up.  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 18 of 84 \n Outcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence  \ncontaining H epatitis B  vaccine during overlapping \nstudy periods 1991 - 199512 and 1991 – 199817. The \nstudy examining a longer window of time  for \nneonates aged <28d, reported 18 deaths among  \n1,771 VAERS reports .17 Causes of death included \naccidental suffocation (1), congenital heart disease \n(1), infection (3), intracerebral hemorrhage (1), and \nSIDS (12).   \n  \n \n \n   \n  \n  \n \nExpected \nneonatal death  One cohort study15 of neonates in the VSD (NCK, SCK) \nsuggested no difference in the proportion of deaths during the \nfirst 29 days of life from expected causes when comparing \nneonates who received Hepatitis B vaccine during the first 29 \ndays of life to neonates who did not [50/72 (69%) vs. 128/196 \n(65%0; p=0.6 ]. 1 Cohort15 \n(N = 268) \n No concerns  No concerns  No concerns  No concerns  Low \nConfidence  \nUnexpected \nneonatal death  One cohort study15 of neonates in the VSD (NCK, SCK) \nsuggested no difference in the proportion of deaths during the \nfirst 29 days of life from unexpected causes when comparing \nneonates who received Hepatitis B vaccine during the first 29 \ndays of life to neonates who did not [22/72 (31%) vs. 68/196 \n(35%); p=0.6 ].  1 Cohort15 \n(N = 268) \n No concerns  No concerns  No concerns  No concerns  Low \nConfidence  \nUnexpected \nneonatal death \nfrom SIDS   One cohort study15 of neonates in the VSD (NCK, SCK) \nsuggested no difference in the death rate from SIDS when \ncomparing neonates who received Hepatitis B vaccine during \nthe first 29 days of life to neonates who did not [8/240,717 \n(3.3 deaths per 105 births) vs. 4/120,979 (3.3 deaths per 105 \nbirths); p=0.99].  1 Cohort15 \n(N = 361,696 ) \n Serious concernsy No concerns  No concerns  No concerns  Very low \nConfidence  \n \nTable 12. GRADE Table: Infection outcomes and administration of the Hepatitis B Vaccine in the first 30 days of life  \nOutcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence  \nAll Infection \noutcomes  Evidence from 1 cohort6 suggests a reduction in risk of having \na blood or CSF culture performed to evaluate a fever, and a \nsuggested reduction in positive blood or CSF cultures , among \ninfants who received a thimerosal -containing Hepatitis  B \nvaccine in the first 21 days of life  when stratifying by age in \ndays . This study also reported no difference in the incidence \nof fever due to infectious reasons.  These results were 2 studies  \n1 Cohort6 \n(N = 5,655)  \n \n \n \n1 DES16  \nNo concerns  \n \n \n \n \n  \nNo concerns  \n \n \n \n \n  \nNo concerns  \n \n \n \n \n  \nNo concerns  \n \n \n \n \n Low \nconfidence  \n \n \n \n \n \n \ny No adjustment for confounding by age at administration, maternal or perinatal risk factors, or years of study.  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 19 of 84 \n Outcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence  \nconsistent in a sub analysis of infants who received the \nHepatitis B  vaccine on the day of birth or day after birth .  \n \n1 case series16 summarizing reports in neonates following \nthimerosal -containing Hepatitis B  vaccine immunization in \nVAERS reported 11 report s coded using  the Medical \nDictionary for Regulatory Activities as “infection and \ninfestation ” in 10 years (2005 – 2015).  (N = 240)  Some \nconcernsz  \nNo concerns   \nNo concerns   \nNo concerns   \nVery low \nconfidence  \nBlood or CSF culture \nperformed  One cohort6 of normal birthweight, full term U.S. infants in the  \nVSD (NCK) suggested there is a reduction in the age -stratified \nrisk of having a blood or CSF culture performed in the first \nthree weeks of life when comparing infants with a record of \nreceiving thimerosal -containing Hepatitis B vaccine in the first \n21 days  of life to infants with no record of Hepatitis B \nvaccination [RR: 0.73 (95%CI: 0.65 -0.82); p <0.001; 133/3,302 \nvs 203/2,353]. This reduction in risk remained consistent in a \nsub-analysis restricting the infants with a record of Hepatitis B \nvaccination on the day of birth or day after birth with infants \nwith no record of Hepatitis B vaccination. [RR: 0.71; (95%CI: \n0.63 -0.80); p <0.001; 126/2,718 vs 203/2,353].  1 Cohort6 \n(N = 5,655)  No concerns  No concerns  No concerns  No concerns  Low \nConfidence  \nBlood or CSF culture \npositive  One cohort6 of normal birthweight, full term U.S. infants in the \nVSD (NCK) suggested there is a reduction in the age -stratified \nrisk of having a positive blood or CSF culture in the first three \nweeks of life when comparing infants with a record of \nreceiving thimerosa l-containing Hepatitis B vaccine in the first \n21 days of life to infants with no record of Hepatitis B \nvaccination [RR: 0.60 (95%CI: 0.38 -0.95); p=0.030; 8/3,302 vs \n16/2,353]. This reduction in risk remained consistent in a sub -\nanalysis restricting the i nfants with a record of Hepatitis B \nvaccination on the day of birth or day after birth  with no \nrecord of Hepatitis B vaccination. [RR: 0.57; (95%CI: 0.35 -0.94); \np <0.027; 7/2,718 vs 16/2,353].  1 Cohort6 \n(N = 5,655)  No concerns  No concerns  No concerns  No concerns  Low \nConfidence  \nFever due to \ninfectious reasons  One cohort6 of normal birthweight, full term, U.S. infants in \nthe Vaccine Safety Datalink (NCK) reported no difference in the \nrisk of a fever due to infectious reasons  in the first three weeks \nof life when comparing infants with a record of receiving \nthimerosal -containing Hepatitis B vaccine in the first 21 days of \nlife to infants with no record of Hepatitis B vaccination during \nthe same time when adjusting  by age in days  [aRR: 0.92 \n(95%CI: 0.7 -1.2); p=0.51; 26/3,302 vs 25/2,353]. This remained 1 Cohort6 \n(N = 5,655)  No concerns  No concerns  No concerns  No concerns  Low \nConfidence  \n \nz Descriptive study, no comparison  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 20 of 84 \n Outcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence  \nconsistent in a sub -analysis restricting the infants with a record \nof Hepatitis B vaccination on the day of birth or day after birth \nwith infants with no record of Hepatitis B vaccination. [RR: \n0.85; (95%CI: 0. 6-1.1); p=0. 28; 21/2,718 vs 25/2,353].  \n \nInfections and \ninfestations  One case series16 (Haber 2018) of reports following single \nantigen thimerosal -containing Hepatitis B vaccine in U.S. \ninfants aged <1 month in VAERS between 2005 - 2015 reported \n4.6% (11/240) non -death serious reports coded using the \nMedical Dictionary for Regulatory Activities as Error! \nBookmark not defined.  “infections and infestations ”. 1 DES16 \n(Haber \n2018)  \n(N = 240)  Some \nconcernsaa No concerns  No concerns  No concerns  Very low \nconfidence  \n \nTable 13. GRADE Table: Local injection site outcomes and administration of the Hepatitis B Vaccine in the first 30 days of life  \nOutcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence  \nAll Local \ninjection site \nreactions  Evidence from five RCTs suggest s no difference in parent reported \nlocal injection site reactions including pain or soreness, swelling, or \nredness or erythema in the first 5 days post -vaccination among \ninfants vaccinated with Engerix -B in the first five days of birth \ncompared with combina tion vaccines or other Hepatitis B  vaccines \nthat were administered at birth or later. One RCT8 suggested an \nincrease in local side effects when comparing doses of Recombivax \nadministered at 2 months of age compared with birth or 18 \nmonths.  5 \nRCT8,9,13,14,18  \n(N = 1, 626) \n \n Some \nconcernsn \n No concerns  No concerns  No concerns  Moderate \nconfidence  \nLocal side effects  One RCT8 of Egyptian infants , compared the outcome of local side \neffects (e.g., local soreness, or temporary redness/induration at the \ninjection site)  1 week after vaccination among infants randomized to \nadministration of the first of dose of Recombivax immediately after \ndelivery, at two months of age, or at 18 months of age, and reported \na higher proportion of local side effects among those who received \nthe vaccine at two months of age (2.8% (5/178) at birth, vs  7.2% \n(12/167) at two months, vs. 1.6% (3/191 ) at 18 months].  No \nrelationship was found between side effects and weight or \nprematurity.  1 RCT8 \n(N = 536) Serious  \nconcernsbb No concerns  No concerns  No concerns  Low \nconfidence  \n \naa No comparison group  \nbb Inadequate randomization, u nclear allocation conce alment and blinding  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 21 of 84 \n Outcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence  \nPain with \nmovement  or \npressure  One RCT9 of healthy Israeli infants , reported no difference in parent \nreports of pain with movement and pain with pressure within 5 days \nof vaccination among infants who received thimerosal -containing \nEngerix -B within 24 hours of birth compared with those who \nreceived thimerosal -containing BioHepB within 24 hours of birth \n[4/52 (7.7%) vs. 4/153 (2.6%)] and [4/52 (7.7%) vs. 2/153 (1.3%)] . \nThe HepB  vaccine  BioHepB is not approved for use in the United \nStates.  1 RCT9 \n(N = 205)  Serious \nconcernscc Some \nconcernsdd No concerns  No concerns  Very l ow \nconfidence  \nPain  or soreness  Two RC T reported a lower proportion of infants with soreness or \npain with the administration of Hepatitis B vaccine  alone at birth \ncompared to the combination  vaccines at any age.  \n• One RCT18 of healthy, full term Australian infants aged five days \nor less reported a higher proportion of parent identified pain at \nthe injection site among those who received co-administration \nof thimerosal -containing Energix -B vaccine and an \ninvestigational acellular pertussis vaccine compared with \nthimerosal -containing Energix -B vaccine alone within 120 hours \nof birth  [41/208 (20%) vs. 14/150 (9%)]. One grade 3 reaction, \ndefined as crying when the limb was moved or pain that \nprevents daily activities, was repo rted in the co -administration \ngroup.  \n• One RCT of healthy U.S. infants14 reported a higher proportion \nparent reports of soreness at the injection site within three days \nof vaccination  with the first lifetime dose of a HBV Vaccine  \namong infants who received Engerix -B alone within 4 days of \nbirth compared with those who received DT aP-HepB  or DT ,  at 2 \nmonths of age compared with those ( 8.1% vs. 35.7%). \n \nOne single group cohort11 of 117 healthy neonates in Colombia who \nreceived the  thimerosal -containing  Engerix -B Hepatitis B vaccine at \nbirth reported 7 (6%) infants experienced pain and 5 (4.3%) \nexperienced severe pain that resolved during the 4 days following \nvaccination.  2 RCT14,18 \n(N = 623) \n \n1 Cohort11 \n(N = 117)  Some \nconcernsee \n \n \n \n \nSome \nconcernsff No concerns  \n \n \n \n \n \nSome concernsh No concerns  \n \n \n \n \n \nNo concerns  No concerns  \n \n \n \n \n \nNo concerns  Low \nconfidence  \n \n \n \n \nVery low \nconfidence  \nRedness or \nerythema  Three RCTs suggest no difference in redness or erythema at the \ninjection site when comparing thimerosal -containing Energix -B \nvaccine at birth with  thimerosal -containing  Energix -B at one month .  3 RCT9,14,18  \n(N = 8 41) \n Some \nconcernsgg \n No concerns  \n \n No concerns  \n \n No concerns  \n \n  \nLow \nconfidence  \n \ncc Unclear allocation concealment ; absence of statistical  analyses  and reporting on protocol deviations  \ndd Small sample size  \nee Unclear allocation concealment and no blinding , unanalyzed loss to follow up  \nff Measurement & misclassification: -1 for unclear day of dosing; -1 for no comparator group  \ngg Unclear allocation concealment and no blinding  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 22 of 84 \n Outcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence  \n• One RCT14 reported no difference in the proportion of  parent \nreports of  redness at the vaccination site within 3 days of \nvaccination  with the first lifetime dose of HBV vaccine  among \ninfants who received Engerix -B within 4 days of birth or \namong those who received DTaP -HepB vaccines at 2 months \nof age (8.8% vs 11.6 %); no grade 3 reactions were reported.  \n• One RCT of Israeli infants9 reported no redness or erythema \nwithin 5 days of vaccination among infants randomized to \nreceipt of  Engerix -B or BioHepB within 24 hours of birth \n(0/52 vs. 0/153 ). The HepB vaccine BioHepB is not approved \nfor use in the United States.  \n• One RCT18 of Australian infants , 57/208 (27%) infants who \nwere co -administered an acellular pertussis vaccine and \nEngerix -B within 120 hours of birth and 30/150 (20%) infants \nwho received Engerix -B alone within 120 hours of birth \nexperienced injection site erythema within 2 days of \nvacci nation. No grade 3 reactions were reported.  \n \nIn one single group cohort11 of 117 Columbian neonates who \nreceived a  thimerosal -containing  Engerix -B Hepatitis B birth dose , 13 \n(11.1%) experienced redness during the 4 days following vaccination; \nthere were no reports of severe redness.   \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n1 DES11 \n(N = 117)   \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nSerious  \nconcernshh  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nSome concerns   \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nNo concerns   \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nNo concerns   \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nVery  low \nconfidence  \nSwelling  Four RCTs  reported no difference in the proportion of parent \nreported swelling for infants who received Engerix -B within 5 days of \nbirth compared with a combination vaccine or a novel vaccine \nadministered in the same timeframe.  \n• In a randomized non -blinded clinical trial18 of Australian \ninfants , 26/208 (12.5%) infants who received an \ninvestigational acellular pertussis vaccine and Engerix -B \nwithin 120 hours of birth and 6/150 (4%) infants who \nreceived Engerix -B within 120 hours of birth experienced \ninjection site swelling within 2 days of vaccina tion. No \ngrade 3 reactions were reported.  \n• One RCT14 of healthy U.S. infants  reported a lower \nproportion of parent reports of swelling at the injection \nsite within three days of the first lifetime dose of a HBV 4 \nRCT9,13,14,18  \n(N = 1,090 ) \n \n \n \n \n \n \n \n \n \n \n Some \nconcernsn \n \n \n \n \n \n \n \n \n \n \n \n No concerns  \n \n \n \n \n \n \n \n \n \n \n \n \n No concerns  \n \n \n \n \n \n \n \n \n \n \n \n \n No concerns  \n \n \n \n \n \n \n \n \n \n \n \n \n Moderate \nconfidence  \n \n \n \n \n \n \n \n \n \n \n \n \n \nhh No blinding, unclear sequence allocation, unanalyzed loss to follow up.  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 23 of 84 \n Outcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence  \nVaccine among those who received Engerix -B alone within \n4 days of birth  and among infants who received DTaP-\nHepB  vaccines  at 2 months of age (0 vs. 16.3%) . \n• One RCT13 of healthy infants in India , reported no cases of \ninjection site swelling among infants vaccinated with \nEngerix -B or infants vaccinated with the HepB Gene Vac -B \nwithin first 2 wks of life (0/ 130 vs. 0/ 132, p=NR). The HepB \nGene Vac -B is not approved for use in the United States.  \n• A RCT9 of Israeli infants  reported a higher proportion of \nswelling at the site within five days of vaccination among \ninfants who received thimerosal -containing Engerix -B \nwithin 24 hours of birth compared with those who \nreceived BioHepB within 24 hours of birth [4/52 (7.7%) vs. \n3/153 (2.0%)]  The HepB vaccine BioHepB is not approved \nfor use in the United States.  \n \nIn a single group cohort11 of 117 neonates in Colombia who received \nan Engerix -B Hepatitis B birth , there were 5 reports of any swelling \n(4.3%), and no reports of severe swelling.   \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n1 DES11 \n(N = 117)   \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nSerious \nconcernsii  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nNo concerns   \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nNo concerns   \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nNo concerns   \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nVery low \nconfidence  \n \nTable 14. GRADE Table: Neurodevelopmental outcomes and administration of the Hepatitis B Vaccine in the first 30 days of life  \nOutcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence  \nAll \nNeurodevelopmental  \noutcomes  The evidence from four  studies report inconsistent results on \nthe association between autism or autism spectrum disorder19-\n21, Emotional disorders / Emotional disturbances19,22 and Tics/ \nTic disorders19,22, and the receipt of an HBV vaccine in the first \nmonth of life . The  strongest study19 report ed no difference  in \nthe adjusted  risk of any of these diagnoses among infants in the 1 Cohort19 \n(N = 110,833)  \n \n4 Case -\ncontrol20,22 -24 \n(N = unclear \ndue to No concerns  \n \n \n \n \n \n No concerns  \n \n \n \n \n \n Some concernsll \n No concerns  \n \n \n \n \n \n Low \nconfidence  \n \n \n \n \n \n \nii Unclear timing of dosing (“at birth”) and no comparison group  \nll Inconsistent results across studies using different inclusion criteria, different analytic approaches, and differences in adj ustment for confounding.  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 24 of 84 \n Outcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence  \nU.S. VSD with  receipt of Hepatitis B vaccine in the first month of \nlife, while the unadjusted case control studies22-24 examined the \nsame infants in the U.S. VSD  and the cross -sectional study of  \nparent interviews  reported an increase in the unadjusted odds \nor adjusted  risk of these diagnoses with  exposure to Hepatitis B \nvaccine in the first month of life . \n \nResults from one cohort19, suggest no difference in the adjusted \nrisk of attention deficit disorder (ADD), coordination disorder, \nspeech or language delay, eating disorders, emotional \ndisturbances, other childhood psychosis, sleep disorders, or \nstammering  among infants in the U.S. VSD   \n \nResults from one case -control study24 of children in the U.S. \nVSD suggests an increase in the risk of diagnoses for s pecific \ndelays in development  among infants who were exposed to a \ndose of thimerosal -containing Hep B vaccine in the first 30 days \nof life compared to those who were not  overlapping \npopulations ) \n \n1 Cross -\nsectional21 \n(N = 7,381)  Serious \nconcernsjj \n \n \n \n \n \nSerious \nconcernskk \n No concerns  \n \n \n \n \n \n \nNo concerns  \n No concerns  \n \n \n \n \n \n \nNo concerns  \n  \nVery low \nconfidence  \n \n \n \n \n \nVery low \nconfidence  \n \nAttention deficit \ndisorder ( ADD ) One cohort study19 of U.S. infants  at three VSD sites (HMO A -C) \nreported no difference in the  risk of an ADD diagnosis after  the \nfirst year of life with the receipt of a thimerosal -containing \nHepatitis  B vaccine  within 1 month of age , when stratified by  \nHMO, year of birth, and sex, and adjusted for birth weight  (HMO \nA: aHR: 0.92 (95%CI 0.52 -1.59 )); adjusted for clinic (HMO B: aHR: \n0.90  (95%CI 0.74 -1.10 )) (HMO C : aHR: 0.88  (95CI% 0.53 -1.48 )). 1 Cohort19 \n(N = 140,887 ) No concerns  No concerns  No concerns  No concerns  Low \nconfidence  \nAutism/Autism \nSpectrum Disorder  Results  from three studies are inconsistent on the  relationship  \nbetween the receipt of  HBV vaccine in the first month of life and \nautism. The largest and strongest study19 (N = 110,833) \nsuggested no relationship between the adjusted risk of a medical \nrecord of an autism diagnosis and HBV vaccine in the first month \nof life , while one case -control study20 and one cross sectional \nstudy that did not adjust for age of administration,  year of \nadministration, or health seeking behaviors, suggested an \nincrease in the odds of HBV vaccination among children with an \nautism diagnosis20 (N=25,939 ) or parent report of an autism \ndiagnosis in  boys21 (N=7,381 ).  \n 1 Cohort19 \n(N = 110,833)  \n \n \n \n \n \n \n \n1 Case -\ncontrol20 \n(N = 25,939)  No concerns  \n \n \n \n \n \n \n \n \n No concerns  \n \n \n \n \n \n \n \n \n \nNo concerns  \n Some \nconcernsoo \n No concerns  \n \n \n \n \n \n \n \n \n \nNo concerns  \n Low \nconfidence  \n \n \n \n \n \n \n \n \nVery low \nconfidence  \n \njj No adjustment age at administration, birthweight, year of administration, cases and controls taken from different study years . \nkk No adjustment for birthweight, age at administration, year of administration taken from different study years, outcome is not  medically validated.  \noo Inconsistent results across studies using different inclusion criteria , different analytic approaches, and differences in adjustment for confounding . \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 25 of 84 \n Outcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence  \n• One cohort study19  of U.S. infants in VSD site HMO B \nreported no difference in the risk of an autism diagnosis \nafter the first year of life with the receipt of a thimerosal -\ncontaining Hep B vaccine within 1 month of age, when \nstratified by year of birth, and sex, and adjus ted for birth \nweight and clinic (HMO B: aHR: 1.16 (95%CI 0.78 -1.71 )). \nMeasures of association not assessed for HMOs with <50 \ncases.  \n• One case -control study20 of children in the U.S. VSD (KPNW, \nKPC), suggested the unadjusted odds of an exposure to  a \ndose of  thimerosal -containing HepB vaccine within the first \nmonth of life  was greater among children with an autism \nspectrum disorder diagnosis  compared to children without \nan autism spectrum diagnosis  [OR: 2.18; (95%CI: 1.74 -2.73); \np<0.00001; 155/ 302 vs 8161 /25632 ]. A cross -sectional \nstudy21 of U.S. boys aged 3 -17 years suggested the odds of a \nparent report of an autism diagnosis was greater among \nboys aged 3 -17 years of age who received the Hepatitis B \nvaccine within 1 month of age born before 1999, when \ncompared to late - or never - vaccinated boys when adjusting \nfor race and ethnicity, family structure, and maternal \neducation [ aOR: 3.002; (95%CI: 1.109 -8.126); p=0.031].   \n1 Cross -\nsectional21 \n(N = 7,381)  Serious \nconcernsmm \n \n \n \nSerious \nconcernsnn \n  \n \n \n \nNo concerns  \n  \n \n \n \nNo concerns  \n  \n \n \n \nVery low \nconfidence  \n \nCoordination \nDisorder  One cohort study19 of U.S. infants in VSD site HMO A  suggested a \npotential increase  in the  risk of a coordination disorder after the \nfirst year of life with the receipt of a thimerosal -containing Hep  B \nvaccine within 1 month of age , when stratified by year of birth, \nand sex, and adjusted for birth weight  (HMO A: aHR: 1.67 ( 95%CI \n0.78-3.57 )). Measures of association not assessed for HMOs with \n<50 cases.  1 Cohort19 \n(N = 13,337)  No concerns  No concerns  No concerns  No concerns  Low \nconfidence  \nSpeech or language \ndelay  One cohort study19 of U.S. infants in three  VSD sites (HMO A -C) \nreported no difference in the  risk of an speech or language delay  \ndiagnosis after the first  year of life with the receipt of a \nthimerosal -containing Hep  B vaccine within 1 month of age , \nwhen stratified by HMO, year of birth, and sex, and adjusted for \nbirth weight  (HMO A: aHR: 1.14 (95%CI 0. 88-1.46 )); adjusted for \nclinic  (HMO B: aHR: 1.03 ( 95%CI 0. 91-1.17)); (HMO C: HR: 0.91 \n(95%CI 0. 79-1.04)).  1 Cohort19 \n(N = 140,887)  No concerns  No concerns  No concerns  No concerns  Low \nconfidence  \nEating disorders  One cohort study19 of U.S. infants in VSD site HMO B reported no \ndifference in the  risk of an eating disorder  diagnosis after the 1 Cohort19 \n(N = 110,833)  No concerns  No concerns  No concerns  No concerns  Low \nconfidence  \n \nmm No adjustment age at administration, birthweight, year of administration , cases and controls taken from different study years.  \nnn No adjustment for birthweight, age at administration, year of administration  taken from different study years , outcome is not medically validated . \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 26 of 84 \n Outcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence  \nfirst year of life with the receipt of a thimerosal -containing Hep  B \nvaccine within 1 month of age , when stratified by year of birth, \nand sex, and adjusted for birth weight  and clinic  HMO B: aHR: \n0.90 ( 95%CI 0. 50-1.61). Measures of association not assessed for \nHMOs with <50 cases.  \nEmotional disorders / \nEmotional \ndisturbances  One cohort study19 of U.S. infants in two VSD sites (HMO A,B) \nreported no difference in the risk of an emotional disturbances \ndiagnosis  (313.8)  after the first year of life with the receipt of a \nthimerosal -containing Hep B vaccine within 1 month of age, \nwhen stratified by HMO, year of birth, and sex, and adjusted for \nbirth weight (HMO A: aHR: 1.00 (95%CI 0.42 -2.36 )); adjusted for \nclinic (HMO B: aHR: 0.76 (95%CI 0.54 -1.07 )). Measures of \nassociation not assessed for HMOs with <50 cases.  \n \nOne case -control study22 of children in the VSD (KPNW, KPC, \nKPNCK) between 1991 – 2000, suggested that the unadjusted \nodds of an expos ure to a thimerosal -containing HepB vaccine \nwithin the first month of life was greater among children with \nICD-9 diagnosis code for emotional disorder (313.xx) than \nchildren without that code in their records  [OR: 1.34; 95 %CI: \n1.12 -1.60; p<0.005, 204/517 vs 9003/27,491]. This association \nremained consistent in a sub -analysis restricted to males [OR: \n1.36; 95% CI: 1.11, 1.66); p<0.005; 158/399 vs  4568/14 ,013) but \nnot females [OR: 1.30; (95% CI: 0.90, 1.89); p=0.15, 46/118 vs \n4435/13 ,478].  1 Cohort19 \n(N = 124,170)  \n \n \n \n \n \n \n \n1 case -control \nstudy22  \n (n=28,008)   \nNo concerns  \n \n \n \n \n \n \n \nSerious \nconcernspp  \nNo concerns  \n \n \n \n \n \n \n \nNo concerns   \nSome  \nconcernsqq \n  \nNo concerns  \n \n \n \n \n \n \n \nNo concerns  Low \nconfidence  \n \n \n \n \n \n \n \nVery low \nconfidence  \nOther childhood \npsychosis  One cohort study19 of U.S. infants in VSD site HMO B reported no \ndifference in the  risk of a otherhood childhood psychosis  \ndiagnosis after the first  year of life with the receipt of a \nthimerosal -containing Hep  B vaccine within 1 month of age , \nwhen stratified by year of birth, and sex, and adjusted for birth \nweight  and clinic  HMO B: aHR: 1.03 ( 95%CI 0. 60-1.74). Measures \nof association not assessed for HMOs with <50 cases.  1 Cohort19 \n(N = 110,833)  No concerns  No concerns  No concerns  No concerns  Low \nconfidence  \nSleep disorders  One cohort study19 of U.S. infants in three  VSD sites (HMO A -C) \nreported no difference in the  risk of a sleep disorder  diagnosis \nafter the first  year of life with the receipt of a thimerosal -\ncontaining Hep  B vaccine within 1 month of age , when stratified \nby HMO, year of birth, and sex, and adjusted for birth weight  \n(HMO A: aHR: 0.79 ( 95%CI 0. 38-1.61 )); adjusted for clinic  (HMO \nB: aHR: 1.24 ( 95%CI 0. 80-1.93)); (HMO C: HR: 0.97 ( 95%CI 0. 79-\n1.19)).  1 Cohort19 \n(N = 140,887)  No concerns  No concerns  No concerns  No concerns  Low \nconfidence  \n \npp No adjustment age at administration, birthweight, year of administration, cases and controls taken from different study years . \nqq Inconsistent results across studies using different inclusion criteria, different analytic approaches, and differences in adj ustment for confounding.  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 27 of 84 \n Outcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence  \nSpecific delays in \ndevelopment   \nOne retrospective cohort study24 of children in the VSD born \nbetween 1991 – 1994,  suggested that the risk  of specific delays \nin development (ICD -9 code 315.xx) was greater among children \nwho were exposed to a thimerosal -containing HepB vaccine \nwithin the first month of life compared to children who were not \nexposed to a thimerosal -containing HepB vaccine in the first \nmonth of life [RR: 1.22, ( 95% CI: 1.12, 1.33), p<0.001, 82 8/18,637 \nvs 1127/31,198]. This association remained consistent in a sub -\nanalysis restricted to males [ RR: 1.23, ( 95%CI: 1.11, 1.37), \np<0.001, 567/9514 vs 771/16,110] and females [ RR: 1.21; (95% \nCI: 1.03, 1.41); p<0. 05, 261/9 ,122 vs 356/15,088].  \n 1 Cohort  \nstudy24 \n(n=49,835 ) Serious \nconcernsrr No concerns  No concerns  No concerns  Very low \nconfidence  \nStammering  One cohort study19 of U.S. infants in two VSD sites (HMO A -C) \nreported no difference in the risk of a stammering diagnosis after \nthe first year of life with the receipt of a thimerosal -containing \nHep B vaccine within 1 month of age, when stratified by HMO, \nyear of birth, and sex, and adjusted for birth weight (HMO  A: \naHR: 0.89 (95%CI 0.40 -1.97)); and adjusted for clinic  in HMO B  \n(HMO B:  aHR: 0.61 (95%CI 0.33 -1.14 )); (HMO C: HR: 0.77 (95%CI \n0.47 -1.26)).  1 Cohort19 \n(N = 140,887 ) No concerns  No concerns  No concerns  No concerns  Low \nconfidence  \nTic Disorder, Tics  One cohort19 and one case control23 examined infants in the U.S. \nVSD during the same time period and reported inconsistent \nresults. When stratifying results by location, year of birth, s ex, \nHMO and clinic, there was no difference in the risk of Tic disorder \namong infants who received a dose of thimerosal -containing Hep \nB vaccine in the first month of life, compared to those who did \nnot19. However , a case control23 using different enrollment \ncriteria and not adjusting for confounding factors . \n• One cohort study19 of U.S. infants in three VSD sites between \n1991 – 1998 (HMO A -C) reported no difference in the risk of \na tics diagnosis after the first year of life with the receipt of a \nthimerosal -containing Hep B vaccine within 1 month of age, \nwhen stratified by HMO, year of birth, and sex, and adjusted \nfor birth weight (HM O A: aHR: 1.25 (95%CI 0.47 -3.29)); \nadjusted for clinic  (HMO B: aHR: 0.85 (95%CI 0.55 -1.30)); \n(HMO C: HR: 0.93 (95%CI 0.45 -1.92)).  1 Cohort19 \n(N = 140,887)  \n \n \n1 Case -\ncontrol23 \n(N = 28,360 ) No concerns  \n \n \n \n \n \nSerious \nConcernsss  \n \nNo concerns  \n \n \n \n \n \n \nNo concerns   \n \nSome \nconcernstt \n  \n \nNo concerns  \n \n \n \n \n \n \nNo concerns   \nLow \nconfidence  \n \n \n \n \n \nVery low \nconfidence  \n \nrr No adjustment age at administration, birthweight, year of administration, cases and controls taken from different study years . \nss Unadjusted for confounding of age at administration, birthweight, healthcare seeking behavior, duration of follow up, and diff erent inclusion criteria & study years for each \ngroup.  \ntt Inconsistent results across studies using different inclusion criteria, different analytic approaches, and differences in adj ustment for confounding.  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 28 of 84 \n Outcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence  \n• One case -control study23 of children in the VSD (KPNW, KPC, \nNCK)  between 1991 - 2000 , suggested the odds of an \nexposure to thimerosal -containing HepB vaccine within the \nfirst month of life  was great er among children with a medical \ndiagnosis code for a tic disorder diagnosis than among those \nwith no tic disorder diagnosis [OR: 1.59; (95%CI: 1.29 -1.98); \np<0.00001; 151/344 vs 9222/28016 ]. This association \nremained consistent in a sub -analysis restricted to males \n[OR: 1.65; (95%CI: 1.29 -2.12); p<0.0001; 113/ 253 vs \n4697/14327 ], but n ot females [OR: 1.45; (95%CI: 0.95 -2.21); \np=0.09; 38/ 91 vs 4525/13 ,689]. \n \nTable 15. GRADE Table: Neurologic outcomes and administration of the Hepatitis B Vaccine in the first 30 days of life  \nOutcome  Summary  Studies  Risk of \nBias  Imprecision  Inconsistency  Indirectness  Confidence  \nAll Neurologic outcomes  The evidence from cohort6 suggest ed there is no \ndifference in the risk of seizures and neurologic disease \nother than seizures  among infants receiving with Hep B \nvaccine in the first 21 days of life, compared to those \nwho did not , and this did not change when restricted \nto those vaccinated in the first day of life . \n \nOne case control study23 did not one case series \nsuggest ed a lower odds of exposure to a thimerosal -\ncontaining hep B vaccine in the first 30 days of life \namong infants diagnosed with  cerebral degeneration \ncompared to those who were not diagnosed.   \n \nTwo case series12,16 identified reports of abnormal CSF, \nconvulsions, and nervous system disorders among the \nreports in the U.S. VAERS between 1991 -1995 and \n2005 – 2015.  1 Cohort6 \n(N = 5,655)  \n \n \n \n1 Case -\ncontrol23 \n(N = \n136,536)  \n \n \n2 Case \nSeries12,16 \n(N = 300 ) No \nconcerns  \n \n \n \n \n \nSerious \nconcernsuu \n \n \n \n \n \nSome \nconcernsvv No concerns  \n \n \n \n \n \n \nNo concerns  \n \n \n \n \n \n \nNo concerns  No concerns  \n \n \n \n \n \n \nNo concerns  \n \n \n \n \n \n \nNo concerns  No concerns  \n \n \n \n \n \n \nNo concerns  \n \n \n \n \n \n \nNo concerns  Low \nconfidence  \n \n \n \n \n \nVery low \nconfidence  \n \n \n \n \n \nVery low \nconfidence  \n \nuu Unadjusted for confounding of age at administration, birthweight, healthcare seeking behavior, duration of follow up, and diff erent inclusion criteria & study years for each \ngroup.  \nvv Descriptive study, no comparison  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 29 of 84 \n Outcome  Summary  Studies  Risk of \nBias  Imprecision  Inconsistency  Indirectness  Confidence  \nAbnormal CSF  In one case series of reports12 following single antigen \nthimerosal -containing Hepatitis B vaccine in U.S. infants \naged <1 month in VAERS between 1991 -1995 , there \nwere 4 (6.7%) serious reports of abnormal CSF . 1 Case \nSeries12 \n(N = 60)  Some \nconcernsww No concerns  No concerns  No concerns  Very low \nconfidence  \nCerebral degeneration  One case -control study23 of children in the VSD (KPNW, \nKPC, NCK), suggested the unadjusted odds of exposure \nto thimerosal -contain ing Hepatitis B vaccine within the \nfirst month of life was lower  among childr en diagnosed \nwith cerebral degeneration than among those without a \ndiagnosis of cerebral degeneration [OR: 0.43; (95%CI: \n0.36 -0.52); p <0.00001; 175/ 647 vs 62637/135 ,889]. 1 Case -\ncontrol23 \n(N = \n136,536)  Serious \nconcernsxx No concerns  No concerns  No concerns  Very low \nconfidence  \nConvulsions  One case series12 of 60 VAERS reports for neonates <0.1 \nyears of age who received a thimerosal -containing \nHepatitis B vaccine between 1991 – 1995 reported 6 \n(10%) reports of convulsions, 4 of which were \nconsidered serious.  1 DES12 \n(N = 60)  Some \nconcernsq  No concerns  No concerns  No concerns  Very low \nconfidence  \nSeizure  One cohort6 of normal birthweight, full term U.S. infants \nin the VSD (NCK) suggested there is no difference in the \nrisk of seizures  in the first three weeks of life when \ncomparing infants with a record of receiving thimerosal -\ncontaining Hepatitis B vaccine in the first 21 days of life \nto infants with no record of Hepatitis B vaccination [RR: \n0.18 (95%CI: 0.02 -1.6); p=0.17; 1/3,302 vs 4/2,353]. This \nremained consistent in a sub -analysis restricting the \ninfants with a record of Hepatitis B vaccination on the \nday of bi rth or day after birth compared  with infants \nwith no record of Hepatitis B vaccination [RR: 0.22; \n(95%CI: 0.02 -1.9); p=0.19; 1/2,718 vs 4/2,353].  1 Cohort6 \n(N = 5,655)  No concerns  No concerns  No concerns  No concerns  Low \nconfidence  \nNervous system disorders  In one case series16 of reports following single antigen \nthimerosal containing Hepatitis B vaccine in U.S. infants \naged <1 month in the VAERS between 2005 - 2015, 6.3% \n(15/240) were non -death serious reports coded  using \nthe Medical Dictionary for Regulatory Activities as \n“Nerv ous Systems Diso rders ”. 1 DES16 \n(N = 240)  Some \nconcernsyy No concerns  No concerns  No concerns  Very low \nconfidence  \nNeurologic disease, other than \nseizure  One cohort6 of normal birthweight, full term U.S. infants \nin the VSD (NCK) suggested there is no difference in the 1 Cohort6 \n(N = 5,655)  No concerns  No concerns  No concerns  No concerns  Low \nconfidence  \n \nww Descriptive study, no comparison  \nxx Unadjusted for confounding of age at administration, birthweight, healthcare seeking behavior,  duration of follow up, and different inclusion criteria & study years for each \ngroup.  \nyy Descriptive study, no comparison  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 30 of 84 \n Outcome  Summary  Studies  Risk of \nBias  Imprecision  Inconsistency  Indirectness  Confidence  \nrisk of neurologic disease in the first three weeks of life \nwhen comparing infants with a record of receiving \nthimerosal -containing Hepatitis B vaccine in the first 21 \ndays of life to infants with no record of Hepatitis B \nvaccination [RR: 1.4 (95%CI: 0.3 -7.8); p=0.99; 4/3,302 vs \n2/2,353]. This remained consistent in a sub -analysis \nrestricting the infants with a record of Hepatitis B \nvaccination on the day of birth or day after birth  \ncompared with infants with no record of Hepatitis B \nvaccination [RR: 1.7; ( 95%CI: 0.3 -9.4); p=0.69; 4/2,718 vs \n2/2,353].  \n \nTable 16. GRADE Table: Cardiopulmonary outcomes and administration of the Hepatitis B Vaccine in the first 30 days of life  \nOutcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence  \nAll Cardiopulmonary \noutcomes  The evidence from one cohort7 suggests that receipt of \nHepatitis B vaccine in the first 24 hours of life is not \nassociated with an increase in the risk of bronchopulmonary \ndysplasia.  \nThe evidence from one case series12 suggests that between \n1991 -1995, 13 of 60 events in VAERS were cardiopulmonary \n(including apnea, bradycardia, and cyanosis) .  2 studies  \n1 Cohort7 \n(N = 818)  \n \n1 DES12 \n(N = 60)  No concerns  \n \nSome \nconcernszz No concerns  \n \n \nNo concerns  No concerns  \n \n \nNo concerns  No concerns  \n \n \nNo concerns  Low \nconfidence  \n \nVery low \nconfidence  \nBronchopulmonary \ndysplasia  One cohort7 of extremely preterm infants (<29 wks gestation) \nin Australia’s Surveillance of Adverse Events Following \nImmunization in the Community suggested there is a reduction \nin the adjusted risk of bronchopulmonary dysplasia when \ncomparing infants with a record o f receiving hepatitis b \nvaccine within 24 hours of birth to infants with no record [aRR: \n0.83; (95%CI: 0.68 -1.0); 155/306 vs 317/512].   1 Cohort7 \n(N = 818)  No concerns  No concerns  No concerns  No concerns  Low \nconfidence  \nApnea  In a case series12 of 60 VAERS reports for neonates <0.1 years \nof age who received a thimerosal -containing Hepatitis B \nvaccine between 1991 – 1995  there were 5 (8.3%) reports of \napnea, 3 of which were considered serious.  1 DES12 \n(N = 60)  Some \nconcernst No concerns  No concerns  No concerns  Very low \nconfidence  \nBradycardia  In a case series12 of 60 VAERS reports for neonates <0.1 years \nof age who received a thimerosal -containing Hepatitis B \nvaccine between 1991 - 1995 , there was 1 (1.7%) serious \nreport of bradycardia.  1 DES12 \n(N = 60)  Some \nconcernst No concerns  No concerns  No concerns  Very low \nconfidence  \n \nzz No comparison group  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 31 of 84 \n Outcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence  \nCyanosis  In a case series12 of 60 VAERS reports for neonates <0.1 years \nof age who received a thimerosal -containing Hepatitis B \nvaccine between 1991 - 1995 , there were 7 (11.7%) reports of \ncyanosis, 5 of which were considered serious.  1 DES12 \n(N = 60)  Some \nconcernst  No concerns  No concerns  No concerns  Very low \nconfidence  \n \nTable 17. GRADE Table: Systemic reactions  and administration of the Hepatitis B Vaccine in t he first 30 days of life  \nOutcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence  \nAll Systemic Reactions  The evidence8-14,18 suggested that systemic reactions do \noccur after vaccination,  and there may be no difference in \nthe occurrence of some outcome when comparing infants \nvaccinated with a Hepatitis B dose in the first 30 days of \nlife compared with those who receive a different vaccine, \nor a Hepatitis B vaccine later or never.  Outcomes for \nwhich the evidence suggests there is no difference include \nfever8-14,18, rash13, constipation13, diarrhea8-10,12 -14,18, \nunusual crying14,18, and vomiting13,14,18 . \n \nSystemic reactions for which the evidence reported \ninconsistent results include anorexia/ decreased \nappetite/ feeding issues9 14,18 and restlessness/ sleeping \nless14,18. The differences in these outcomes may be due to \nparent perceptions (all were based on parent reports), \ndifferences in vaccines, or differences in outcome \ndefinitions used across these studies.  \n \nEvidence was sufficient to determine that agitation12 \noccurs  in 13 of 60 neonatal U.S. VAERS reports between \n1991 -1995, but not sufficient to determine if this is \ndifferent from the rate of occurrence in the general \nneonatal population.  5 \nRCT8,9,13,14,18  \n(N = 1,627)  \n \n1 cohort10 \n(N = 10,829)  \n \n \n2 DES11,12 \n (N = 177)  Some concerns \naaa \n \n \nSerious \nconcernsbbb \n \nSome \nconcernsccc \n No concerns  \n \n \n \nNo concerns  \n \n \n \nNo concerns  \n No concerns  \n \n \n \nNo concerns  \n \n \n \nNo concerns  \n No concerns  \n \n \n \nNo concerns  \n \n \n \nNo concerns  \n Moderate  \nconfidence  \n \n \nVery low \nconfidence  \n \n \nVery low \nconfidence  \n \nAgitation  In a case series12 of 60 VAERS reports for neonates <0.1 \nyears of age who received a thimerosal -containing \nHepatitis B vaccine between 1991 – 1995 , there were 13 \n(21.7%) reports of agitation, 7 of which were considered \nserious.  \n 1 DES12  \n(N = 60)  Some \nconcernsccc  No concerns  No concerns  No concerns  Very low \nconfidence  \n \naaa Unclear allocation concealment and no blinding  \nbbb No adjustment for confounding, unclear presence of outcomes at start of study  \nccc Descriptive study, no comparator  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 32 of 84 \n Outcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence  \nAnorexia/Decreased \nappetite/ Feeding \nIssues  Three RCTs of healthy infants reported inconsistent results  \nfor the outcome of decreased appetite . That may be \nattributable to differences in the comparator vaccine or \nthe timing of comparator vaccine or the differences in \noutcome definitions used in each study.  \n• One RCT14 of full -term U.S. infants reported a higher \nproportion of decreased appetite within 3 days of \nvaccination among infants who received DTPa -HepB, \nOPV, and Hib vaccines at 2 months of age compared \nwith those who received Engerix -B within 4 days of \nbirth [25. 6% of 129 vs 14% of 136; ] . \n• In a RCT of Israeli infants9, 0/52  infants who received \nEngerix -B within 24 hours of birth and 3/153 (2.0%) \nwho received BioHepB within 24 hours of birth \nexperienced anorexia within 5 days of vaccination. \nThe HepB vaccine BioHepB is not approved for use in \nthe United States.  \n• In a randomized non -blinded clinical trial of \nAustralian infants18, 28/221 (13%) infants who \nreceived an investigational acellular pertussis \nvaccine and Engerix -B within 120 hours of birth and \n17/103 (17%) infants who received Engerix -B within \n120 hours of birth experienced feeding issues within \n2 days of vaccination. On e grade 3 feeding reaction \n(defined as preventing normal activities or requiring \nsignificant medical intervention) was reported \namong the 103 infants (0.9%) who received only \nEngerix within 120 hours of birth.  \n \nOne single group cohort of 117 Columbian neonates11 who \nreceived an Engerix -B Hepatitis B birth dose, 3 (2.6%) \nexperienced a loss of appetite during the 4 days following \nvaccination, 1.7% (2/117) were considered severe . In one \nsingle group cohort of 117 Columbian neonates who \nreceived an Engerix -B Hepatitis B birth dose (Lopez 2002), \n3 (2.6%) experienced a loss of appetite during the 4 days \nfollowing vaccination, 1.7% (2/117) were considered \nsevere . 3 RCTs9 14,18  \n(N = 794)  \n \n \n \n \n \n1 DES11 \n (N = 117)  Some \nconcernsddd \n \n \n \n \n \nSome \nconcernseee No concerns  \n \n \n \n \n \n \n \nNo concerns   \n \n \n \nSome \nconcernsfff \n No concerns  \n \n \n \n \n \n \n \nNo concerns  \nModerate \nconfidence  \n \n \n \n \n \n \nVery low \nconfidence  \n \nddd Unanalyzed loss to follow up  \neee Descriptive study, no comparator, unclear timing of dosing (“at birth”)  \nfff Inconsistent results across studies using different inclusion criteria, different analytic approaches, and differences in adj ustment for confounding.  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 33 of 84 \n Outcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence  \nConstipation  One RCT of healthy infants in India13 reported no cases of \nconstipation in infants vaccinated with Engerix -B in the first \n2 weeks of life or in infants vaccinated with HepB Gene \nVac-B within first 2 weeks of life (0/130 vs. 0/132). The \nHepB Gene Vac -B is not approved for use in the United \nStates.  1 RCT13  \n(N = 262)  No concerns  No concerns  No concerns  No concerns  High \nconfidence  \nDiarrhea  Four RCTs suggested no difference in the proportion of \ndiarrhea cases among infants who received the HBV \nvaccine in the first 2 weeks of life or less, and those who \nreceive the dose later, or a different vaccine.  \n• One RCT of Israeli infants9, reported no \ndifference in diarrhea or vomiting within 5 days \nof vaccination among infants who received \nEngerix -B within 24 hours of birth and who \nreceived BioHepB within 24 hours of birth0/52 \nvs. 1/153 (0.64%). The HepB vaccine BioHepB is \nnot approved for use in the United States.  \n• One RCT14 of full -term U.S. infants reported no \ndifference in the proportion of parents reporting \ndiarrhea within 4 days of birth when comparing \ninfants who received Engerix B within 3 days of \nbirth and infants who received DTaP -HepB, OPV, \nand Hib vaccines at 2 mon ths of age, (8.1% vs. \n10.1%). There was no difference in the \nproportion experiencing a grade 3 reaction \n(defined as preventing normal activities) (0.7% \nvs. 0).  \n• One RCT of healthy infants in India13 reported no \ncases of loose motions in infants vaccinated with \nEngerix -B in the first 2 weeks of life or in infants \nvaccinated with HepB Gene Vac -B within first 2 \nweeks of life (0/130 vs. 0/132, p=NR). The HepB \nGene Vac -B is not approved for use in the United \nStates.  \n• In a RCT of Australian infants18, 38/221 (17.0%) \ninfants who received an investigational acellular \npertussis vaccine and Engerix -B within 120 hours \nof birth and 12/103 (12%) infants who received \nEngerix -B within 120 hours of birth experienced 4 RCT9,13,14,18  \n(N = 927)  \n \n \n1 DES12 \n(N = 60)  \n Some \nconcernsggg \n \n \n \nSome \nconcernshhh \n  \n \nNo concerns  \n \n \n \nNo concerns  \n \n \n \n \n  \n \nNo concerns  \n \n \n \nNo concerns  \n \n \n \n \n  \n \nNo concerns  \n \n \n \nNo concerns  \n \n \n \n \n Low \nconfidence  \n \n \nVery low \nconfidence  \n \nggg Unclear allocation concealment, no blinding, unclear assessment of loss to follow up  \nhhh Descriptive study, no comparator  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 34 of 84 \n Outcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence  \ndiarrhea within 2 days of vaccination. No grade 3 \nreactions (defined as preventing normal activities \nor requiring significant medical intervention) \nwere reported.  \n \nIn one case series12 of 60 VAERS  reports for neonates <0.1 \nyears of age who received a thimerosal -containing \nHepatitis B vaccine between 1991 – 1995 , there was 1 \nreport of diarrhea, which was not categorized as serious.  \nDrowsiness or sleeping \nmore  Two RCTs report inconsistent results for increased \ndrowsiness when comparing Engerix B as a birth dose with \nDTPA -HepB14 or both acellular pertussis and Engerix -B \nvaccines18 at 2 months of age. Inconsistencies may be \nexplained by the different comparison vaccine or by the \ndifferent outcome definitions of “increased sleep” and \n“drowsiness”  \n• One RCT14 of full -term U.S. infants reported a \nlower proportion of parents reporting increased \ninfant sleep within 3 days of birth when \ncomparing infants who received Engerix B within \n4 days of birth and infants who received DTPa -\nHepB, OPV, and Hib vaccines at 2 mo nths of age, \n(32.4% vs. 40.3%). There was higher proportion \nof infants receiving Engerix B within 4 days of \nbirth whose parents reported them experiencing \na grade 3 reaction (defined as preventing normal \nactivities) (2.9% vs. 0.8%).  \n• One RCT of Australian infants18 reported a higher \nproportion of parents reported drowsiness within \n2 days of vaccination among parents of infants \nwho received Engerix -B within 120 hours of birth \ncompared with infants who received an \ninvestigational acellular pertussis vaccine and \nEngeri x-B within 120 hours of birth and [29/103 \n(28%) vs. 39/221 (18%)]. There was no difference \nin drowsiness of grade 3 severity (defined as \npreventing normal activities or requiring \nsignificant medical intervention) between those  \n2 RCTs14,18 \n(N = 591)  \n \n1 DES11  \n(N = 117)  \n  \n \n \n \n \nSome \nconcernsiii \n \n \n \n \n \nSome \nconcernsjjj \n \n \n \n \n No concerns  \n \n \n \n \n \n \n \nNo concerns  Some \nconcernskkk \n  \n \n \n \n \nNo concerns  \n \n \n \n \n \n \n \n \nNo concerns  \n \n \n \n \n Very low \nconfidence  \n \n \n \n \n \n \n \nVery low \nconfidence  \n \niii Unclear allocation concealment and no blinding  \njjj Descriptive study, no comparator  \nkkk Inconsistent results across studies using different inclusion criteria, different analytic approaches, and differences in adj ustment for confounding.  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 35 of 84 \n Outcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence  \nreceiving the both acellular pertussis and \nEngerix -B vaccines and by 1 (0.9%) of the infants \nreceiving only Engerix -B vaccines at birth (1/221 \n(0.5%) vs. 1/103 (0.9%).  \nAmong a single group cohort of 117 Columbian neonates11 \nwho received an Engerix -B Hepatitis B birth dose (Lopez \n2002), 6 (5.1%) experienced drowsiness during the 4 days \nfollowing vaccination; 1 (0.9%) was reported to be severe.  \n \nFever   \nFive RCT suggested no difference in parent reports of fever \nbetween infants vaccinated with HBV vaccines in the first \ntwo weeks of life and infants vaccinated with the same \nvaccine HBV vaccine at later ages, different HBV vaccines at \nthe same age, or diffe rent HBV and HBV combination \nvaccines at lat er ages.  \n• One RCT of Egyptian infants8, reported no difference \nin parent reports of fever (reported as 1 -2 days of low -\ngrade fever ≤102⁰F) among those vaccinated with \nRecombinant HB vaccine immediately after birth \n(5.6% n=178), at 2 months (7.2%, n=167), or 18 \nmonths of age (2.1%, n=191). No relationship was \nfound between side effects and weight or \nprematurity.  \n• In a randomized non -blinded clinical trial of Australian \ninfants18, reported no difference in parent reports of \nfever ≥38⁰C within 2 days of vaccination among \ninfants who received an investigational acellular \npertussis vaccine and Engerix -B within 120 hours of \nbirth and infants who received Engerix -B within 120 \nhours of birth (0/221 vs 1/138 (0.7%)). No fevers \n≥39⁰C were reported among participants in either \narm.  \n• One RCT of Israeli infants9 reported no difference in a \ntemperature ≥38 ⁰C within 5 days of vaccination  \ninfants who re ceived Engerix -B within 24 hours of \nbirth compared with those who received BioHepB \nwithin 24 hours of birth [0/52 vs. 2/153 (1.3%)]. The \nHepB vaccine BioHepB is not approved for use in the \nUnited States.   \n \n \n5 \nRCT8,9,13,14,18  \n(N = 1,627)  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n  \n \n \n \nSome concerns \nlll \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n  \n \n \n \n \nNo concerns  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n  \n \n \n \n \nNo concerns  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n  \n \n \n \n \nNo concerns  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n  \n \n \n \n \nLow \nconfidence  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nlll Unclear allocation concealment and no blinding  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 36 of 84 \n Outcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence  \n• One RCT of full -term U.S. infants14 reported no \ndifference in fever (defined as rectal temperature \n≥38⁰C within 4 days of vaccination among infants who \nreceived Engerix B within 3 days of birth and infants \nwho received DTPa -HepB, OPV, and Hib vaccines at 2 \nmonths of age, (5.9%, n = 136 vs. 14.7%, n=129). \nThere was also no difference in parent reports grade 3 \nreaction (defined as temperature >39.5 ⁰C ) (0% vs. \n0.8%).  \n• An RCT of healthy infants in India13 reported no \ndifference in parent -reported fever (defined as axillary \ntemperature ≥38⁰C) in infants vaccinated wit h \nEngerix -B in the first 2 weeks of life and infants \nvaccinated with HepB Gene Vac -B within first 2 weeks \nof life [6/130 (4.6%) vs. 4/132 (3.0%)].  \n \nIn a cohort study of full -term Israeli infants10, 68/5,819 \n(1.2%) full -term infants receiving hepatitis B vaccination \nand 27/5,010 (0.54%) full -term infants not receiving \nhepatitis B vaccine had a birth hospitalization discharge \ndiagnosis of “neonatal fever” above 37.5 C (p<0.001). \nFevers above 38C were  noted in 50 (0.9%) of vaccinated \ninfants and 27 (0.54%) of unvaccinated infants (p<0.05).  \nIdentifiable causes of fever (e.g. sepsis, dehydration, \nmaternal fever, respiratory distress) were noted among 15 \nvaccinated infants (0.3%) and 13 unvaccinated i nfants \n(0.3%). Unexplained fevers were noted among 35 (0.6%) \nvaccinated infants and 14 (0.3%) unvaccinated infants \n(p=0.013).  \n \n \nTwo single group studies, one cohort and one case series of \nadverse reports in neonates who received HBV vaccine as a \nbirth does or within 1 month reported identified 18 U.S. \nVAERS reports of fever between 1991 – 1995, and 13 \nserious U.S. VAERS reports of fever, and reported 1 severe \nfever among 117 Columbian neonates,  \n• Among a cohort of 117 Columbian neonates11 who \nreceived an Engerix -B Hepatitis B birth dose, 1 (0.9%) \nexperienced a severe fever during the 4 days following  \n \n \n \n \n \n \n \n \n \n \n \n1 cohort10 \n(N = 10,829)  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n2 DES 11,12 \n(N = 177)  \n \n \n \n \n \n \n  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nSerious \nconcernsmmm \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nNo concerns  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nNo concerns  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nNo concerns  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nVery low \nconfidence  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nmmm No adjustment for confounding, unclear presence of outcomes at start of study  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 37 of 84 \n Outcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence  \nvaccination (severe: >39⁰C axillary or >39.5⁰C rectal). In \na case series12 of 60 VAERS reports for n eonates <0.1 \nyears of age who received a thimerosal -containing \nHepatitis B vaccine between 1991 – 1995 , there were \n18 (30%) reports of fever, 13 of which were \nconsidered serious. Median number of days from \nvaccination to onset of fever was 1 day and mean \nmaximum temperature was 38.9 ⁰C (range: 38.0 -\n40.6 ⁰C). Of 10 infants with follow -up from fever, all 10 \nhad recovered.   \n \nSome \nconcernsnnn \n  \n \nNo concerns  \n  \n \nNo concerns  \n  \n \nNo concerns  \n  \n \nVery low \nconfidence  \n \nIrritability or fussiness  Three RCTs report inconsistent results for irritability or \nfussiness among infants vaccinated with Engerix B within \n24h9, 3 days14, and 120 hours of birth18. These differences \ncould be due to timing of birth dose, differences in \noutcome definitions, or comparison vaccine.  \n• One RCT14 of full -term U.S. infants reported a \nlower proportion of parents reporting irritability \nor fussiness within 3 days of vaccination when \ncomparing infants who received Engerix B within \n4 days of birth and infants who received DTPa -\nHepB, OPV, and Hib vaccine s at 2 months of age, \n(22.1% vs. 54.3%).  \n• One randomized non -blinded clinical trial of \nAustralian infants18 reported no difference in \nirritability within 2 days of vaccination among \ninfants who received an investigational acellular \npertussis vaccine and Engerix -B within 120 hours \nof birth compared with infants who received \nEngerix -B within 120 hours of birth [5 4/221 \n(24.0%) vs.21/103 (20%)]. There was also no \ndifference in Grade 3 irritability reactions \nreported by parents (defined as preventing \nnormal activities or requiring significant medical \nintervention) [2/221 (0.9%) vs. 1/103 (0.9%)].  \n• One RCT of Israeli infants9 reported a higher \nproportion of irritability among infants who 3 RCT9,14,18   \n(N = 794)  \n \n1 DES11 \n(N = 117)  \n Serious \nconcernsooo \n \n \n \n \n \nSome \nconcernsppp No concerns  \n \n \n \n \n \n \nNo concerns  Some \nconcernsqqq \n No concerns  \n \n \n \n \n \n \nNo concerns  Very low \nconfidence  \n \n \n \n \n \nVery low \nconfidence  \n \nnnn Descriptive study, no comparator  \nooo Unclear allocation concealment and no blinding, no assessment of loss to follow up or missing data  \nppp \n Descriptive study, no comparator  \nqqq Inconsistent results across studies using different inclusion criteria, different analytic approaches, and differences in adj ustment for confounding.  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 38 of 84 \n Outcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence  \nreceived Engerix -B within 24 hours of birth and \n[6/52 (11.5%) vs. 5/153 (3.3%)] who received \nBioHepB within 24 hours of birth experienced \nirritability within 5 days of vaccination. The HepB \nvaccine BioHepB is not approved for use in the \nUnited States.  \n \nOne cohort of 117 Columbian neonates11 who received an \nEngerix -B Hepatitis B birth dose, reported 3 (2.6%) infants \nexperienced irritability during the 4 days following \nvaccination; 2 cases (1.7%) were reported to be severe.  \n \nRash  One RCT of healthy infants in India13 reported no cases of \nrashes in infants vaccinated with Engerix -B in the first 2 \nweeks of life or in infants vaccinated with HepB Gene Vac -B \nwithin first 2 weeks of life (0/130 vs. 0/132, p=NR). The \nHepB vaccine BioHepB is not approved for use in the \nUnited States.  \n \nIn a case series12 of 60 VAERS reports for neonates <0.1 \nyears of age who received a thimerosal -containing \nHepatitis B vaccine between 1991 – 1995 were 2 serious \nreports (3.3%) reports of rash that included fever.  1 RCT13 \n (N = 262)  \n \n \n \n \n \n1 DES12  \n(N = 60)  \n \n No Concerns  \n \n \n \n \n \n \n \nSome \nconcernsrrr \n \n No concerns  \n \n \n \n \n \n \n \nNo concerns  \n \n \n No concerns  \n \n \n \n \n \n \n \nNo concerns  \n \n \n No concerns  \n \n \n \n \n \n \n \nNo concerns  \n \n \n High \nconfidence  \n \n \n \n \n \n \nVery low \nconfidence  \n \n \n \nRestlessness or \nsleeping less  Two randomized trials of full -term infants reported \ninconsistent results for restlessness and sleeping less which \ncould be due to the differences in outcome definition, \ntiming of HepB birth dose, or comparator vaccine.  \n• One randomized trial14 of full -term U.S. infants \nreported a lower proportion of parents reporting \nrestlessness or sleeping less within 3 days of \nvaccination when comparing infants who received \nEngerix B within 4 days of birth and infants who \nreceived DTPa -HepB, OPV, and Hib vac cines at 2 \nmonths of age, (16.9% vs. 26.4%; ).  \n• One randomized non -blinded clinical trial of Australian \ninfants18 reported was a higher proportion of parent 2 RCT14,18 \n(N = 585)  \n \n Serious \nconcernssss No concerns  Some \nconcernsttt No concerns  Very Low \nconfidence  \n \nrrr Descriptive study, no comparator  \nsss Unclear allocation concealment and no blinding, no assessment of loss to follow up.  \nttt Inconsistent proportions for Engerix -B associated symptoms, and inconsistent directionality of comparisons  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 39 of 84 \n Outcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence  \nreports of restlessness within 2 days of vaccination \namong of infants who received Engerix -B within 120 \nhours of birth compared to infants who received an \ninvestigational acellular pertussis vaccine and Engerix -\nB within 120 hours of birth  [32/103 (31%) vs .  49/221 \n(22.0%)].  There was no difference in parent reports of \ngrade 3 restless reactions (defined as preventing \nnormal activities or requiring significant medical \nintervention) [3/103 (3%) vs. 2/221 (1%)].  \n \nUnusual crying   \nOne RCT14 of full -term U.S. infants reported a no difference \nin parent reports of unusual crying within 4 days of \nvaccination when comparing infants who received Engerix -\nB within 3 days of birth and those who received DTPa -\nHepB, OPV, and Hib vaccines at 2 months of  age (1.5% of \n136 infants vs. 3.1% of 129 infants). Results were similar \nfor parent reports of grade 3 unusual crying (defined as \npreventing normal daily activity) (0 vs. 0.8%).  1 RCT14 \n(N = 136)  Some \nconcernsuuu No concerns  No concerns  No concerns  Moderate \nconfidence  \nVomiting  Three RCTs suggested no difference in the incidence \nvomiting when comparing infants who received HBV at \nbirth with those who received HBV 1 month after birth, \ninfants who received a different HBV at birth, or infants \nwho received HBV co -administered with a n acellular \npertussis vaccine.  \n• One RCT14 of full -term U.S. infants reported no \ndifference in the incidence of vomiting within 4 days \nof vaccination as reported by parents between infants \nwho received Engerix -B within 3 days of birth and \nthose who received DTPa -HepB, OPV, and Hib \nvaccines at 2 mo nths of age (4.4% of 136 infants vs. \n7.8% of 129 infants). None reported a grade 3 reaction \nof vomiting.  \n• One RCT of healthy infants in India13 reported no \ncases of vomiting among infants who received \nEngerix -B or GeneVac -B within 30 days of birth. (0/130 \nv. 0/132) GeneVac -B is not approved for use in the \nU.S. 3 RCT13,14,18  \n(N = 853)  \n \n Some \nconcernsvvv No concerns  No concerns  No concerns  Moderate \nconfidence  \n \nuuu -1 absence of randomization & blinding, and no assessment of loss to follow up.  \nvvv -1 absence of randomization & blinding, and no assessment of loss to follow up.  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 40 of 84 \n Outcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence  \n• In a randomized non -blinded clinical trial of Australian \ninfants18, 45/221 (20.0%) infants who received an \ninvestigational acellular pertussis vaccine and Engerix -\nB within 120 hours of birth and 23/103 (24%)  infants \nwho received Engerix -B within 120 hours of birth \nexperienced vomiting within 2 days of vaccination. No \ngrade 3 vomiting reactions (defined as preventing \nnormal activities or requiring significant medical \nintervention) were reported.  \n \nTable 18. GRADE Table: Other outcomes and administration of the Hepatitis B Vaccine in the first 30 days of life  \nOutcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence  \nAll Other  outcomes  One case control25 reported an increase in the odds of \nthimerosal -containing Hep atitis B vaccine exposure  in the \nfirst month of life  among children with an ICD9 code for \npremature puberty in their HMO medical records, compared \nto children without the code , and when stratified by sex, this \nincrease was seen among females but not males.  \n \nOne  case series16 of VAERS reports following single antigen \nthimerosal containing H epatitis B vaccine  between 2000 – \n2015 reported ten reports coded  using the Medical Dictionary \nof Regulatory Activities of “general disorders and \nadministration site conditions ” in 15 years ( 10/240) ; and an \nearlier  case series12 of VAERS reports of U.S. neonates  with \nHepB exposure  between 1991 – 1995 reported one report  for \nHyperbilirubenemia /HbSAg+ (1/60) . \n  \n1 case \ncontrol25 \n(N=58,675)  \n \n2 DES12,16 \n(n=300) \n Serious \nconcerns  \n \n \nSome \nconcernswww No concerns  \n \n \n \n \nNo concerns  No concerns  \n \n \n \n \nNo concerns  No concerns  \n \n \n \n \nNo concerns  Very low \nconfidence  \n \n \n \nVery low \nconfidence  \nPremature puberty  One case -control study25 of children enrolled in the VSD \n(KPNW, KPC, KPNC) suggested the odds of exposure to to \nthimerosal -containing HepB vaccine with in the first month of \nlife was greater among children w ith a medical record of am \nICD9 code for  premature puberty  compared to children who \ndid not   [OR: 1.80, (95% CI: 1.51, 2.16), p<0.00001; 255/ 486 vs \n20582/54199 ]. When stratified by sex, the association was \nobserved among females [OR: 1.87, (95% CI: 1.55, 2.25, 1 case \ncontrol25 (N \n= 58,685)  Serious \nconcernsxxx No concerns  No concerns  No concerns  Very low \nconfidence  \n \nwww Descriptive study, no comparison  \nxxx -2 Very serious concerns for confounding factors such as prematurity or birthweight, age at administration, or year of adminis tration.  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 41 of 84 \n Outcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence  \np<0.00001), 245/ 458 vs 9997/26209 ] but not among males \n[OR: 0.91, (95% CI: 0. 42, 1.98), p>0.99; 10/ 28 vs 10584/27989 ]. \nGeneral disorders \nand administration \nsite conditions  One case series16 of reports following single antigen thimerosal \ncontaining Hepatitis B vaccine in U.S. infants aged <1 month in \nVAERS between 2005 – 2015, reported 4.2% ( 10/240) - were \ncoded using the Medical Dictionary for Regulatory Activities \n(MedDRA) as general  disorders and administration site \nconditions ”. 1 DES16 \n(N = 240)  \n Some \nconcernsyyy No concerns  No concerns  No concerns  Very low \nconfidence  \nHyperbilirubenemia \n/HbSAg+  In a case series12 of 60 VAERS  reports for neonates <0.1 years \nof age who received a thimerosal -containing Hepatitis B \nvaccine  between 1991 -1995 , there was 1 (1.7%) serious report \nof hyperbilirubenemia/HbSAg+.  1 DES12 \n(N = 60)  Some \nconcernsh Some concernszzz No concerns  No concerns  Very low \nconfidence  \n \n  \n \nyyy Descriptive study, no comparison  \nzzz Small sample size  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 42 of 84 \n C. Extracted Evidence from Included Studies  \nC.1. Study Characteristics for All Included Studies  \nTable 19. Characteristics of Studies Meeting Inclusion Criteria  \nAuthor Year  Study design  Data Collection P eriod  Sample size, N  Surveillance System (if Applicable)  Country  \nBassily 19958 Randomized \nControlled Trial  Not reported  536 infants  Not reported  Egypt  \nEriksen 200415 Retrospective \ncohort  January 1, 1993 - December \n31, 1998  361,696 newborns in Kaiser SCK & \nNCK HMO birth cohort  \n \n268 neonatal deaths analyzed for \nexpected and unexpected death  Vaccine Safety Datalink   \n(Kaiser Permanente, Southern California  and Kaiser \nPermanente Northern California ) United States  \nGallagher \n201021 Cross -sectional  1997 -2002  7,381 boys aged 3 -17 Not reported  United States  \nGeier  \n201320 Case -control  1991 -1999  Not reported  \n25,939 infants in analysis  Vaccine Safety Datalink  United States  \nGeier 201523 Case control  1991 -2000  28,360 (344 cases with tics: 253 \nmale, 91 female; 28,016 controls, \n14,327 males, 13,689 females)  \n \n136,536 ( 647 cases  with cerebral \ndegeneration: 359 male, 288 \nfemale; 135,888 controls, 69,426  \nmales, 66,462 females)  Vaccine Safety Datalink  \nUnited States  \nGeier 201624 Retrospective \ncohort  1991 -2000  49,835 children  Vaccine Safety Datalink  United States  \nGeier 201722 Nested case \ncontrol  1991 -2000  28,008 children  Vaccine Safety Datalink   \n(Kaiser Permanente North -West  and Kaiser Permanente \nNorthern California ) United States  \nGeier 201825 Case  control  1991 -2000  54,685 children  Vaccine Safety Datalink  United States  \nGreenberg \n200214 Randomized \nTrial  Not reported  280 infants  Kaiser Permanente, Southern California  United States  \nHaber 201816 Case series  January  1, 2005 – \nDecember  31, 2015  20,231 VAERS reports  Vaccine Adverse Event Reporting System  United States  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 43 of 84 \n Author Year  Study design  Data Collection P eriod  Sample size, N  Surveillance System (if Applicable)  Country  \nLewis 20016 Cohort  November  1, 1991 – \nApril 30, 1994  5,655 normal birthweight,  full term \ninfants  Vaccine Safety Datalink  (Northern California Kaiser \nPermanente)  United States  \nLinder 199910 Cohort  Birth/record  \nJanuary  1, 1991 – \nDecember  31, 1992  10,829 neonates  Not reported  Israel  \nLopez 20 0211 Cohort  NR 117 neonates  Centro Materno Infantil Los Farallones  Colombia  \nMorgan 20257 Cohort  January  1, 2017 – \nDecember  31, 2020  818 extremely preterm infants  Surveillance of Adverse Events Following Immunization \nin the Community  Australia  \nNiu 199612 Case series  January  1, 1991 – \nMay 31, 1995  12,520 VAERS reports  Vaccine Adverse Event Reporting System  United States  \nNiu 199917 Case series  January  1, 1991 – \nOctober  5,1998  1,771  Vaccine Adverse Event Reporting System  United States  \nSapru 200713 Randomized \nControlled Trial  \n(control arm)  Not reported  262 Not reported  India  \nVerstraeten \n200319 Retrospective \ncohort study  1995 -end of 2000  140,887  at 3 HMOs ( 13,337 at A, \n110,833 at B, 16,717 at C)  Vaccine Safety Datalink  United States  \nWood 201818 Randomized \nControlled Trial  June 11, 2010 - March 14, \n2013  440 Not reported  Australia  \nYerushalmi \n19979 Randomized \nControlled Trial  Not reported  205 (46% were male)  Not reported  Israel  \n \n \n \n \n \n \n \n \n \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 44 of 84 \n C.2. Outcomes for All Included Studies  \nTable 20. Adverse Events Following Immunization (AEFI)  Results of Studies Meeting Inclusion Criteria  \nStudy  Study \nType  Outcome  Outcome \nIdentification  Intervention \n(Thimerosal \nY/N/NR)  Intervention \n% (n/N)  Control  \n(Thimerosal \nY/N/NR)  Control \n% (n/N)  p-value  Measure of \nAssociation  Adjusted  Risk of Bias  \nNiu \n199612 Case \nseries  Cerebral venous \nthrombosis/intraventricular \nhemorrhage   NR HepB vaccine \n(unspecified ) \nin neonates \naged <0.1 \nyears  (Y) 1.7% (1/60)  NR NR NR NR NR Some \nconcernsaaaa  \nNiu \n199612 Case \nseries  Disseminated intravascular \ncoagulation   NR HepB vaccine \n(unspecified) \nin neonates \naged <0.1 \nyears (Y)  1.7% (1/60)  NR NR NR NR NR Some \nconcernsa  \nNiu \n199612 Case \nseries  Necrotizing enterocolitis   NR HepB vaccine \n(unspecified) \nin neonates \naged <0.1 \nyears (Y)  1.7% (1/60)  NR NR NR NR NR Some \nconcernsbbbb  \nLope z \n200211 Cohort  Serious adverse events   Unsolicited \nsymptoms \ncollected \nduring 30 -day \nfollow -up \nwindow  HepB Engerix -\nB at birth ( Y) 0.9% (1/117)  NR NR NR NR NR Some \nconcerns2  \n \nTable 21. Allergic Reaction and Atopy Results of Studies Meeting Inclusion Criteria  \nStudy  Study \nType  Outcome  Outcome \nIdentification  Intervention \n(Thimerosal \nY/N/NR)  Intervention \n% (n/N)  Control  \n(Thimerosal \nY/N/NR)  Control % \n(n/N)  p-\nvalue  Measure of \nAssociation  Adjusted  Risk of \nBias  \nLewis \n20016 Cohort  Allergic \nreaction  ICD 10 Codes  Hep B Vax \n(unspecified) \nwithin first 21 d \n(Y) <0.1% \n(1/3302)  Unvaccinated \nwithin first 21 d  <0.1% \n(1/2353)  NR RR: 0.71 (0.04 -\n11.4); p = 0.99  None  Some \nconcerns  \n \naaaa Descriptive study, no comparison  \nbbbb Descriptive study, no comparison  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 45 of 84 \n Study  Study \nType  Outcome  Outcome \nIdentification  Intervention \n(Thimerosal \nY/N/NR)  Intervention \n% (n/N)  Control  \n(Thimerosal \nY/N/NR)  Control % \n(n/N)  p-\nvalue  Measure of \nAssociation  Adjusted  Risk of \nBias  \nLewis \n20016 Cohort  Allergic \nreaction  ICD 10 Codes  Hep B Vax \n(unspecified) \nwithin day of birth \nor day after birth \n(Y) <0.1% \n(1/2718)  Unvaccinated \nwithin first 21 d <0.1% \n(1/2937)  NR RR: 0.87 (0.05 -\n13.8); p = 0.99  None  Some \nconcerns  \nSapru \n200713 RCT Eczema  Parent assessment \nor medical exam  HepB  \nEngerix -B within \nfirst 2 wks  0 (0/130)  HepB  \nGene Vac -B within \nfirst 2 wks  0 (0/132)  NA NR NR No \nconcerns  \n \nTable 22. All Death Outcomes Results of Studies Meeting Inclusion Criteria  \nStudy  Study \nType  Outcome  Outcome \nIdentification  Intervention \n(Thimerosal \nY/N/NR)  Intervention \n% (n/N)  Control  \n(Thimerosal \nY/N/NR)  Control % \n(n/N)  p-value  Measure of \nAssociation  Adjusted  Risk of Bias  \nGreenberg  \n200214 RCT All -cause \nmortality   NR; at 7 \nmonths follow -\nup Engerix -B \nvaccine at \nbirth, 1 \nmonth, and 6 \nmonths of \nage and \nDTaP , OPV, \nand Hib \nvaccines  at 2, \n4, and 6 \nmonths of \nage ( NR) 0% (0/1 40) DTaP -HepB , \nOPV , and Hib  \nvaccine s at 2, \n4, and 6 \nmonths of \nage 0% (0/ 140)  NR NR NR Some \nconcernse  \nMorgan  \n20257 Cohort  All -cause \nmortality   Victorian \nDeaths index; \nall cause \nmortality \noccurring in \nthe 3 months \nafter birth  Hep B vaccine \n(unspecified) \nwithin  24h of \nbirth  for \nextremely \npremature \ninfants (<29 \nweeks \ngestation)  \n(NR)  2.30% (7/306)  No recorded \nHep B \nvaccine \nwithin 24h of \nbirth  for \nextremely \npremature \ninfants (<29 \nweeks \ngestation)  2.70% \n(14/512)  NR aRR: 1.13; \n(95%CI: 0.42 -\n2.81)  Maternal \nage, low \nApgar at 1 \nminute, low \nApgar at 5 \nminutes, \nmaternal \nsmoking, \ngestation \nperiod and \ncongenital \nheart No concerns   \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 46 of 84 \n Study  Study \nType  Outcome  Outcome \nIdentification  Intervention \n(Thimerosal \nY/N/NR)  Intervention \n% (n/N)  Control  \n(Thimerosal \nY/N/NR)  Control % \n(n/N)  p-value  Measure of \nAssociation  Adjusted  Risk of Bias  \ndisease \nstatus  \nHaber  \n201816 Case series  All -cause \nmortality   VAERS reports \nof death \nverified by \ndeath \ncertificate or \nautopsy report  Hep B vaccine \n(unspecified) \ninfants aged \n<1 month  (Y) 11.3% \n(27/240 ) NR NR NR NR NR Some  \nconcernscccc  \nNiu \n199612 Case series  All -cause \nmortality   VAERS reports \nof death  Hep B vaccine \n(unspecified) \ninfants aged \n<0.1 yrs of \nage (Y) 10% (6/60)  NR NR NR NR NR Some \nconcernsdddd \nNiu \n199917 Case series  All -cause \nmortality   VAERS reports \nof death  Hep B vaccine \n(unspecified) \ninfants aged \n<28 days (Y)  1% ( 18/1771 ) NR NR NR NR NR Some  \nconcernseeee  \nEriksen  \n200415 Cohort  Expected \nneonatal \ndeath   ICD-9 codes \nand \ndetermined by \nmedical \nautopsy ; four \ncategories \nconsidered \nexpected  Hep B vaccine \n(unspecified) \nbefore 29 \ndays of age \n(Y); 85% \nvaccinated of \nday of birth, \nnone  beyond \n8 days of life  69% (50/72)  No HepB \nvaccine with \ndeath at <29 \ndays of age  65% \n(128 /196)  0.6 NR NR No concerns   \nEriksen  \n200415 Cohort  Unexpected \nneonatal \ndeath   ICD-9 codes \nand \ndetermined by \nmedical \nautopsy  Hep B vaccine \n(unspecified) \nbefore 29 \ndays of age \n(Y); 85% \nvaccinated of \nday of birth, \nnone beyond \n8 days of life  31% (22/72)  No HepB \nvaccine with \ndeath at <29 \ndays of age  35% \n(68/196)  0.6 NR NR No concerns   \n \ncccc Descriptive study, no comparison  \ndddd Descriptive study, no comparison  \neeee Descriptive study, no comparison  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 47 of 84 \n Study  Study \nType  Outcome  Outcome \nIdentification  Intervention \n(Thimerosal \nY/N/NR)  Intervention \n% (n/N)  Control  \n(Thimerosal \nY/N/NR)  Control % \n(n/N)  p-value  Measure of \nAssociation  Adjusted  Risk of Bias  \nEriksen  \n200415 Cohort  Unexpected \nneonatal \ndeath from \nSIDS   ICD-9 codes \nand \ndetermined by \nmedical \nautopsy  Hep B vaccine \n(unspecified) \nbefore 29 \ndays of age \n(Y); 85% \nvaccinated of \nday of birth, \nnone beyond \n8 days of life  8/240,717 \n(3.3 deaths \nper 100,000 \nbirths)  No HepB \nvaccine at \n<29 days of \nage 4/120,979 \n(3.3 deaths \nper 100,000 \nbirths)  0.99  NR NR Serious \nconcerns27  \n \nTable 23. Infection Results of Studies Meeting Inclusion Criteria  \nStudy  Study Type  Outcome  Outcome \nIdentification  Intervention \n(Thimerosal \nY/N/NR)  Intervention \n% (n/N)  Control  \n(Thimerosal \nY/N/NR)  Control % \n(n/N)  p-value  Measure of \nAssociation  Adjusted  Risk of Bias  \nLewis  \n20016 Cohort  Blood or CSF \nculture \nperformed   Clinical \nlaboratory \ndata  Hep B vaccine \n(unspecified) \nwithi n first 21 \ndays of life (Y)  4% \n(133/3,302 ) No Hep B \nvaccine \nwithin first \n21 days of \nlife 8.6% \n(203/2,353 ) <0.001  RR: 0.73 \n(95%CI: 0.65 -\n0.82)  NR No concerns   \nLewis  \n20016 Cohort  Blood or CSF \nculture \nperformed   Clinical \nlaboratory \ndata  Hep B vaccine \n(unspecified) \non day  of \nbirth or day \nafter birth  (Y) 4.6% \n(126/2,718 ) No Hep B \nvaccine \nwithin first \n21 days of \nlife 8.6% \n(203/2,353 ) <0.001  RR: 0.71; \n(95%CI: 0.63 -\n0.80)  NR No concerns   \nLewis  \n20016 Cohort  Blood or CSF \nculture \npositive   Clinical \nlaboratory \ndata  Hep B vaccine \n(unspecified) \nwithin first 21 \ndays of life (Y)  0.2% \n(8/3,302 ) No Hep B \nvaccine \nwithin first \n21 days of \nlife 0.7% \n(16/2,353 ) 0.030  RR: 0.60 \n(95%CI: 0.38 -\n0.95)  NR No concerns   \nLewis  \n20016 Cohort  Blood or CSF \nculture \npositive   Clinical \nlaboratory \ndata  Hep B vaccine \n(unspecified) \non day of \nbirth or day \nafter birth (Y) 0.3% \n(7/2,718 ) No Hep B \nvaccine \nwithin first \n21 days of \nlife 0.7% \n(16/2,353 ) 0.027  RR: 0.57; \n(95%CI: 0.35 -\n0.94)  NR No concerns   \nLewis  \n20016 Cohort  Fever  (in first \n3 weeks of \nlife) ICD-9 codes, \ncomputerized \ndatabase \nsearch  Hep B vaccine \n(unspecified) \nwithin first 21 \ndays of life (Y)  (26/3,302 ) No Hep B \nvaccine \nwithin first (25/2,353 ) 0.51  aRR: 0.92 \n(95%CI: 0.7 -\n1.2) Adjusted by \nage in days  No concerns   \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 48 of 84 \n Study  Study Type  Outcome  Outcome \nIdentification  Intervention \n(Thimerosal \nY/N/NR)  Intervention \n% (n/N)  Control  \n(Thimerosal \nY/N/NR)  Control % \n(n/N)  p-value  Measure of \nAssociation  Adjusted  Risk of Bias  \n21 days of \nlife \nLewis  \n20016 Cohort  Fever  (in first \n3 weeks of \nlife) ICD-9 codes, \ncomputerized \ndatabase \nsearch  Hep B vaccine \n(unspecified) \non day of \nbirth or day \nafter birth (Y) (21/2,718 ) No Hep B \nvaccine \nwithin first \n21 days of \nlife (25/2,353 ) 0.28 aRR: 0.85; \n(95%CI: 0. 6-\n1.1) Adjusted by \nage in days  No concerns   \nHaber  \n201816 Case series  Infections \nand \ninfestations   VAERS, non -\ndeath, serious \nreports  Hep B vaccine \n(unspecified) \ninfants aged \n<1 month (Y)  4.6%  (11/240)  NR NR NR NR NR Some \nconcerns7  \n \nTable 24. Local Injection -site Outcomes Results of Studies Meeting Inclusion Criteria  \nStudy  Study \nType  Outcome  Outcome \nIdentification  Intervention \n(Thimerosal \nY/N/NR)  Intervention \n% (n/N)  Control  \n(Thimerosal \nY/N/NR)  Control \n% (n/N)  p-\nvalue  Measure of \nAssociation  Adjusted  Risk of \nBias \nBassily \n19958 RCT Local side effects  Parental report of \nlocal soreness or \ntemporary \nredness/induration at \nthe injection site  Recombivax \nimmediately \nafter  birth (Y)  2.8% ( 5/178)  Recombivax \nat 18 months \nof age (Y)  1.6% \n(3/191)  NR NR NR Serious \nconcerns8  \nBassily  \n19958 RCT Local side effects  Parental report of \nlocal soreness or \ntemporary \nredness/induration at \nthe injection site  Recombivax \nat 2 months of \nage (Y)  7.2% ( 12/167)  Recombivax \nat 18 months \nof age (Y)  1.6% \n(3/191)  NR NR NR Serious \nconcerns8  \nYerushalmi  \n19979 RCT Pain with movement   Parental report on \ndiary card for 5 days \npost -vaccination  Engerix -B \nvaccine within \n24 hrs of birth \n(Y) 7.7% (4/52)  BioHepB \nvaccine within \n24 hrs of birth \n(Y) 2.6% \n(4/153)  NR NR NR Serious \nconcerns9  \nYerushalmi  \n19979 RCT Pain with pressure   Parental report on \ndiary card for 5 days \npost -vaccination  Engerix -B \nvaccine within \n24 hrs of birth \n(Y) 7.7% (4/52)  BioHepB \nvaccine within \n24 hrs of birth \n(Y) 1.3% \n(2/153)  NR NR NR Serious \nconcerns9  \nWood  \n201818 RCT Pain or soreness  (any)  Parental report of \npain at injection site \nwithin 2 days after \ndose  Engerix -B \nvaccine given \nalone within \n120 hrs of 9% (14/150)  Engerix -B co-\nadministered \nwith \ninvestigational 20% \n(41/208)  NR NR NR Some \nconcerns11 \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 49 of 84 \n Study  Study \nType  Outcome  Outcome \nIdentification  Intervention \n(Thimerosal \nY/N/NR)  Intervention \n% (n/N)  Control  \n(Thimerosal \nY/N/NR)  Control \n% (n/N)  p-\nvalue  Measure of \nAssociation  Adjusted  Risk of \nBias \nbirth (Y ); \n87.6 % \nvaccinated \ndays 0 -2 acellular \nPertussis \nvaccine within \n120 hrs of \nbirth (Y ); 91% \nvaccinated \ndays 0-2 \nWood  \n201818 RCT Pain or soreness  \n(severe)  Parental report of \npain at injection site \nwithin 2 days after \ndose , severe classified \nas crying when limb is \nmoved/spontaneously \npainful or prevents \ndaily activities  Engerix -B \nvaccine given \nalone within \n120 hrs of \nbirth (Y ); \n87.6 % \nvaccinated \ndays 0 -2 0% (0/150)  Engerix -B co-\nadministered \nwith \ninvestigational \nacellular \nPertussis \nvaccine within \n120 hrs of \nbirth (Y ); 91% \nvaccinated \ndays 0-2 0.5% \n(1/208)  NR NR NR Some \nconcerns11 \nGreenberg  \n200214 RCT Pain or soreness  (Any)  Solicited parental \nreport for day of \nvaccination and 3 \ndays following \nvaccination  Engerix -B \nvaccine within \n4 days of birth  \n(NR)  8.1%  \n(NR/136)  DTaP -HepB , \nOPV, and Hib \nvaccines  at 2 \nmonths of age \n(NR)  35.7%  \n(NR/129)  NR NR NR Some \nconcerns11 \nGreenberg  \n200214 RCT \nPain or soreness (Grade \n3/Severe)  Solicited parental \nreport for day of \nvaccination and 3 \ndays following \nvaccination ; Grade 3 -\nsoreness that caused \ncrying when limb was \nmove d; reported  at \nany vaccination site  Engerix -B \nvaccine within \n4 days of birth  \n(NR)  \n0% (0/136)  DTaP -HepB, \nOPV, and Hib \nvaccines at 2 \nmonths of age \n(NR)  1.6% \n(NR/129)  NR NR NR Some \nconcerns11 \nLopez  \n200211 Cohort  Pain or soreness  (Any)  Solicited self -report  \nby diary card during \n4-day follow -up \nwindow  HepB Engerix -\nB at birth ( Y) 6% (7/117)  NR NR NR NR NR Some \nconcerns12  \nLopez  \n200211 Cohort  Pain or soreness \n(Severe)  Solicited self -report \nby diary card during \n4-day follow -up \nwindow  HepB Engerix -\nB at birth (Y)  4.3% (5/117)  NR NR NR NR NR Some \nconcerns12  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 50 of 84 \n Study  Study \nType  Outcome  Outcome \nIdentification  Intervention \n(Thimerosal \nY/N/NR)  Intervention \n% (n/N)  Control  \n(Thimerosal \nY/N/NR)  Control \n% (n/N)  p-\nvalue  Measure of \nAssociation  Adjusted  Risk of \nBias \nWood  \n201818 RCT Redness or \nerythema  (Any)  Parental report , \nwithin 2 days of dose; \ngrade 1: <10mm, \ngrade 2 -10-<30mm; \ngrade 3: >=30mm  Engerix -B \nvaccine given \nalone within \n120 hrs of \nbirth (Y) ; \n87.6 % \nvaccinated \ndays 0 -2 20% (30/150)  Engerix -B co-\nadministered \nwith \ninvestigational \nacellular \nPertussis \nvaccine within \n120 hrs of \nbirth (Y ); 91% \nvaccinated \ndays 0-2 27% \n(57/208)  NR NR NR Some \nconcerns13  \nWood  \n201818 RCT Redness or \nerythema  (Severe/Grade \n3) Parental report, \nwithin 2 days of dose; \ngrade 3: >=30mm  Engerix -B \nvaccine given \nalone within \n120 hrs of \nbirth (Y ); \n87.6 % \nvaccinated \ndays 0 -2 0 Engerix -B co-\nadministered \nwith \ninvestigational \nacellular \nPertussis \nvaccine within \n120 hrs of \nbirth (Y ); 91% \nvaccinated \ndays 0-2 0 NR NR NR Some \nconcerns13  \nYerushalmi  \n19979 RCT Redness or erythema   Parental report on \ndiary card for 5 days \npost -vaccination  Engerix -B \nvaccine within \n24 hrs of birth \n(Y) 0/52  BioHepB \nvaccine within \n24 hrs of birth \n(Y) 0/153  NR NR NR Some \nconcerns14  \nGreenberg  \n200214 RCT Redness or \nerythema  (Any)  Solicited parental \nreport for day of \nvaccination and 3 \ndays following \nvaccination  Engerix -B \nvaccine within \n4 days of birth  \n(NR)  8.8% \n(NR/136)  DTaP -HepB, \nOPV, and Hib \nvaccines at 2 \nmonths of age \n(NR)  11.6% \n(NR/129)  NR NR NR Some \nconcerns14  \nGreenberg  \n200214 RCT Redness or \nerythema  (Severe/Grade \n3) Solicited parental \nreport for day of \nvaccination and 3 \ndays following \nvaccination ; Grade 3 -\ndiameter >20mm; \nreported at any \nvaccination site  Engerix -B \nvaccine within \n4 days of birth  \n(NR)  0% (0/136)  DTaP -HepB, \nOPV, and Hib \nvaccines at 2 \nmonths of age \n(NR)  0% \n(0/129)  NR NR NR Some \nconcerns14  \nLopez  \n200211 Cohort  Redness or \nerythema  (Any)  Solicited self -report \nby diary card during HepB Engerix -\nB at birth ( Y) 11.1% \n(13/117)  NR NR NR NR NR Serious \nconcerns15  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 51 of 84 \n Study  Study \nType  Outcome  Outcome \nIdentification  Intervention \n(Thimerosal \nY/N/NR)  Intervention \n% (n/N)  Control  \n(Thimerosal \nY/N/NR)  Control \n% (n/N)  p-\nvalue  Measure of \nAssociation  Adjusted  Risk of \nBias \n4-day follow -up \nwindow  \nLopez  \n200211 Cohort  Redness or \nerythema  (Severe)  Solicited self -report \nby diary card during \n4-day follow -up \nwindow; severe \n>20mm  HepB Engerix -\nB at birth (Y)  0% (0/117)  NR NR NR NR NR Serious \nconcerns15  \nSapru  \n200713 RCT Swelling  Parental report until \ntotal follow -up period \nof 18 weeks  Engerix -B \nvaccine within \nfirst 2 weeks \nof life (NR)  0% (0/130)  GeneVacB \n(HepB) \nvaccine within \nfirst 2 weeks \nof life (NR)  0% \n(0/132)  NR NR NR Some \nconcernsn  \nGreenberg  \n200214 RCT Swelling  (Any)  Solicited parental \nreport for  day of \nvaccination and  3 \ndays following \nvaccination  Engerix -B \nvaccine within \n4 days of birth  \n(NR)  0% (0/136)  DTaP -HepB, \nOPV, and Hib \nvaccines at 2 \nmonths of age \n(NR)  16.3% \n(NR/129)  NR NR NR Some \nconcernsn  \nGreenberg  \n200214 RCT Swelling  (Severe/Grade \n3) Solicited parental \nreport for day of \nvaccination and 3 \ndays following \nvaccination ; Grade 3 -\ndiameter >20mm; \nreported at any \nvaccination site  Engerix -B \nvaccine within \n4 days of birth  \n(NR)  0% (0/136)  DTaP -HepB, \nOPV, and Hib \nvaccines at 2 \nmonths of age \n(NR)  3.1% \n(NR/129)  NR NR NR Some \nconcernsn  \nYerushalmi  \n19979 RCT Swelling  Parental report on \ndiary card for 5 days \npost -vaccination  Engerix -B \nvaccine within \n24 hrs of birth \n(Y) 7.7% (4/52)  BioHepB \nvaccine within \n24 hrs of birth \n(Y) 2.0% \n(3/153)  NR NR NR Some \nconcernsn  \nWood  \n201818 RCT Swelling  (Any)  Parental report, \nwithin 2 days of dose; \ngrade 1: <10mm, \ngrade 2 -10-<30mm; \ngrade 3: >=30mm  Engerix -B \nvaccine given \nalone within \n120 hrs of \nbirth (Y) ; \n87.6 % \nvaccinated \ndays 0 -2 4% (6/150)  Engerix -B co-\nadministered \nwith \ninvestigational \nacellular \nPertussis \nvaccine within \n120 hrs of \nbirth (Y ); 91% \nvaccinated \ndays 0-2 12.5% \n(26/208)  NR NR NR Some \nconcerns16  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 52 of 84 \n Study  Study \nType  Outcome  Outcome \nIdentification  Intervention \n(Thimerosal \nY/N/NR)  Intervention \n% (n/N)  Control  \n(Thimerosal \nY/N/NR)  Control \n% (n/N)  p-\nvalue  Measure of \nAssociation  Adjusted  Risk of \nBias \nWood  \n201818 RCT Swelling (Severe/Grade \n3) Parental report, \nwithin 2 days of dose; \ngrade 3: >=30mm  Engerix -B \nvaccine given \nalone within \n120 hrs of \nbirth (Y ); \n87.6 % \nvaccinated \ndays 0 -2 0 Engerix -B co-\nadministered \nwith \ninvestigational \nacellular \nPertussis \nvaccine within \n120 hrs of \nbirth (Y ); 91% \nvaccinated \ndays 0-2 0 NR NR NR Some \nconcerns16  \nLopez  \n200211 Cohort  Swelling  (Any)  Solicited self -report \nby diary card during \n4-day follow -up \nwindow  HepB Engerix -\nB at birth (Y)  4.3% (5/117)  NR NR NR NR NR Serious \nconcerns17  \nLopez  \n200211 Cohort  Swelling  (Severe)  Solicited self -report \nby diary card during \n4-day follow -up \nwindow; severe \n>20mm  HepB Engerix -\nB at birth (Y)  0% (0/117)  NR NR NR NR NR Serious \nconcerns17  \n \nTable 25. Neurodevelopmental Results of Studies Meeting Inclusion Criteria  \nStudy  Study \nType  Outcome  or \nCase  Outcome \nIdentification  Intervention \nor Exposure \n(Thimerosal \nY/N/NR)  Intervention \nor Exposure % \n(n/N)  Control  \n(Thimerosal \nY/N/NR)  Control % (n/N)  p-value  Measure of \nAssociation  Adjusted  Risk of \nBias \nVerstraeten  \n200319 Cohort  Attention \ndeficit \ndisorder \n(ADD )  ICD-9 codes  HepB vaccine \n(unspecified) \nwithin 1 \nmonth of age \nat HMO A (Y)  (Not stratified \nby dose timing)  NR NR NR aHR: 0.92 \n(95%CI 0.52 -\n1.59)  Stratified \nby HMO, \nyear of \nbirth, and \nsex, and \nadjusted \nfor birth \nweight  No \nconcerns   \nVerstraeten  \n200319 Cohort  Attention \ndeficit \ndisorder \n(ADD )  ICD-9 codes  HepB vaccine \n(unspecified) \nwithin 1 (Not stratified \nby dose timing)  NR NR NR aHR: 0.90 \n(95%CI 0.74 -\n1.10)  Stratified \nby HMO, \nyear of \nbirth, and No \nconcerns   \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 53 of 84 \n Study  Study \nType  Outcome  or \nCase  Outcome \nIdentification  Intervention \nor Exposure \n(Thimerosal \nY/N/NR)  Intervention \nor Exposure % \n(n/N)  Control  \n(Thimerosal \nY/N/NR)  Control % (n/N)  p-value  Measure of \nAssociation  Adjusted  Risk of \nBias \nmonth of age \nat HMO B  (Y) sex, and \nadjusted \nfor birth \nweight  \nand clinic  \nVerstraeten  \n200319 Cohort  Attention \ndeficit \ndisorder \n(ADD )  Costar codes  HepB vaccine \n(unspecified) \nwithin 1 \nmonth of age \nat HMO C  (Y) (Not stratified \nby dose timing)  NR NR NR HR: 0.88 \n(95CI% 0.53 -\n1.48)  none  No \nconcerns   \nVerstraeten  \n200319 Cohort  Autism/Autism \nSpectrum \nDisorder   ICD-9 codes  HepB vaccine \n(unspecified) \nwithin 1 \nmonth of age \nat HMO B (Y)  (Not stratified \nby dose timing)  NR NR NR aHR: 1.16 \n(95%CI 0.78 -\n1.71)  Stratified \nby HMO, \nyear of \nbirth, and \nsex, and \nadjusted \nfor birth \nweight  \nand clinic  No \nconcerns   \nGeier  \n201320 Case -\ncontrol  Autism/Autism \nSpectrum \nDisorder   ICD-9 codes  HepB vaccine \n(unspecified) \n(Y) or \ncombined \nHib-HepB \nvaccine or no \nvaccine \nwithin first \nmonth of life \nfor cases \n(diagnosed \nwith autism \nspectrum \ndisorder)  Exposure/Cases:  \n(155/302)  HepB vaccine \n(unspecified) \n(Y) or \ncombined \nHib-HepB \nvaccine or no \nvaccine \nwithin first \nmonth of life \nfor controls \n(no diagnosis \nof autism \nspectrum \ndisorder)  Exposure/Controls: \n(8161/ 25632)  <0.00001  OR: 2.18; \n(95%CI: \n1.74 -2.73)  \n(assessed as \nOR of \nexposure to \nthimerisol -\ncontaining \nvaccine in \ncases v. \ncontrols)  NR Serious \nconcerns38  \nGallagher  \n201021 Cross -\nsectional  Autism/Autism \nSpectrum \nDisorder   Parent \nreported \nautism \ndiagnosis to \nNational \nHealth HepB vaccine \n(unspecified) \nwithin 1 \nmonth of age \nin males born \nbefore 1999 \n(NR)  NR No HepB \nvaccine \n(unspecified) \nin first \nmonth of life \n(vaccinated \nlate or never NR 0.031  aOR: 3.002; \n(95%CI: \n1.109 -8.126)  when \nadjust ing \nfor race  \nand \nethnicity , \nfamily \nstructure, Serious \nconcerns39  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 54 of 84 \n Study  Study \nType  Outcome  or \nCase  Outcome \nIdentification  Intervention \nor Exposure \n(Thimerosal \nY/N/NR)  Intervention \nor Exposure % \n(n/N)  Control  \n(Thimerosal \nY/N/NR)  Control % (n/N)  p-value  Measure of \nAssociation  Adjusted  Risk of \nBias \nInterview \nSurvey  vaccinated) \nin males \nborn before \n1999 (NR)  and \nmaternal \neducation  \nVerstraeten  \n200319 Cohort  Coordination \nDisorder   ICD-9 codes  HepB vaccine \n(unspecified) \nwithin 1 \nmonth of age \nat HMO A (Y)  (Not stratified \nby dose timing)  NR NR NR aHR: 1.67 \n(95%CI 0.78 -\n3.57)  Stratified \nby HMO, \nyear of \nbirth, and \nsex, and \nadjusted \nfor birth \nweight  No \nconcerns   \nVerstraeten  \n200319 Cohort  Speech or \nlanguage \ndelay   ICD-9 codes  HepB vaccine \n(unspecified) \nwithin 1 \nmonth of age \nat HMO A (Y)  (Not stratified \nby dose timing)  NR NR NR aHR: 1.14 \n(95%CI 0.88 -\n1.46)  Stratified \nby HMO, \nyear of \nbirth, and \nsex, and \nadjusted \nfor birth \nweight  No \nconcerns  \nVerstraeten  \n200319 Cohort  Speech or \nlanguage \ndelay   ICD-9 codes  HepB vaccine \n(unspecified) \nwithin 1 \nmonth of age \nat HMO B (Y)  (Not stratified \nby dose timing)  NR NR NR aHR: 1.03 \n(95%CI 0.91 -\n1.17)  \n Stratified \nby HMO, \nyear of \nbirth, and \nsex, and \nadjusted \nfor birth \nweight  \nand clinic  No \nconcerns  \nVerstraeten  \n200319 Cohort  Speech or \nlanguage \ndelay   Costar codes  HepB vaccine \n(unspecified) \nwithin 1 \nmonth of age \nat HMO C (Y)  (Not stratified \nby dose timing)  NR NR NR HR: 0.91 \n(95%CI 0.79 -\n1.04)  none  No \nconcerns  \nVerstraeten  \n200319 Cohort  Eating \ndisorders   ICD-9 codes  HepB vaccine \n(unspecified) \nwithin 1 \nmonth of age \nat HMO B (Y)  (Not stratified \nby dose timing)  NR NR NR aHR: 0.90 \n(95%CI 0.50 -\n1.61)  Stratified \nby HMO, \nyear of \nbirth, and \nsex, and \nadjusted No \nconcerns   \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 55 of 84 \n Study  Study \nType  Outcome  or \nCase  Outcome \nIdentification  Intervention \nor Exposure \n(Thimerosal \nY/N/NR)  Intervention \nor Exposure % \n(n/N)  Control  \n(Thimerosal \nY/N/NR)  Control % (n/N)  p-value  Measure of \nAssociation  Adjusted  Risk of \nBias \nfor birth \nweight  \nand clinic  \nGeier  \n201722 Case -\ncontrol  Emotional \ndisorders   ICD-9 codes  HepB vaccine \n(unspecified) \n(Y) or \ncombined \nHib-HepB \nvaccine or no \nvaccine \nwithin first \nmonth of life \nfor cases \n(diagnosed \nwith \nemotional \ndisorders)  Exposure/Cases:  \n(204/513)  HepB vaccine \n(unspecified) \n(Y) or \ncombined \nHib-HepB \nvaccine or no \nvaccine \nwithin first \nmonth of life \nfor controls \n(no diagnosis \nof emotional \ndisorders)  Exposure/Controls:  \n(9003/ 27491)  <0.005  OR: 1.34 (95 \n%CI: 1.12 -\n1.60 ) \n(assessed as \nOR of \nexposure to \nthimerisol -\ncontaining \nvaccine in \ncases v. \ncontrols)  none  Serious \nconcerns41  \nGeier  \n201722 Case -\ncontrol  Emotional \ndisorders   ICD-9 codes  HepB vaccine \n(unspecified) \n(Y) or \ncombined \nHib-HepB \nvaccine or no \nvaccine \nwithin first \nmonth of life \nfor male \ncases \n(diagnosed \nwith \nemotional \ndisorders)  Exposure/Cases:  \n(158/ 399)  HepB vaccine \n(unspecified) \n(Y) or \ncombined \nHib-HepB \nvaccine or no \nvaccine \nwithin first \nmonth of life \nfor male \ncontrols (no \ndiagnosis of \nemotional \ndisorders)  Exposure/Controls:  \n(4568/ 14013)  <0.005  OR: 1.36; \n(95% CI: \n1.11 -1.66 ) \n(assessed as \nOR of \nexposure to \nthimerisol -\ncontaining \nvaccine in \ncases v. \ncontrols)  Stratified \nby sex  Serious \nconcerns41  \nGeier  \n201722 Case -\ncontrol  Emotional \ndisorders   ICD-9 codes  HepB vaccine \n(unspecified) \n(Y) or \ncombined \nHib-HepB \nvaccine or no \nvaccine \nwithin first Exposure/Cases:  \n(46/118)  HepB vaccine \n(unspecified) \n(Y) or \ncombined \nHib-HepB \nvaccine or no \nvaccine \nwithin first Exposure/Controls:  \n(4435/13478)  0.15  OR: 1.30; \n(95% CI: \n0.90 -1.89)  \n(assessed as \nOR of \nexposure to \nthimerisol -\ncontaining Stratified \nby sex  Serious \nconcerns41  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 56 of 84 \n Study  Study \nType  Outcome  or \nCase  Outcome \nIdentification  Intervention \nor Exposure \n(Thimerosal \nY/N/NR)  Intervention \nor Exposure % \n(n/N)  Control  \n(Thimerosal \nY/N/NR)  Control % (n/N)  p-value  Measure of \nAssociation  Adjusted  Risk of \nBias \nmonth of life \nfor female \ncases \n(diagnosed \nwith \nemotional \ndisorders)  month of life \nfor female \ncontrols (no \ndiagnosis of \nemotional \ndisorders)  vaccine in \ncases v. \ncontrols)  \nVerstraeten  \n200319 Cohort  Emotional \ndisturbances   ICD-9 codes  HepB vaccine \n(unspecified) \nwithin 1 \nmonth of age \nat HMO A (Y)  (Not stratified \nby dose timing)  NR NR NR aHR: 1.00 \n(95%CI 0.42 -\n2.36)  Stratified \nby HMO, \nyear of \nbirth, and \nsex, and \nadjusted \nfor birth \nweight  No \nconcerns   \nVerstraeten  \n200319 Cohort  Emotional \ndisturbances   ICD-9 codes  HepB vaccine \n(unspecified) \nwithin 1 \nmonth of age \nat HMO B (Y)  (Not stratified \nby dose timing)  NR NR NR aHR: 0.76 \n(95%CI 0.54 -\n1.07)  Stratified \nby HMO, \nyear of \nbirth, and \nsex, and \nadjusted \nfor birth \nweight  \nand clinic  No \nconcerns   \nVerstraeten  \n200319 Cohort  Other \nchildhood \npsychosis   ICD-9 codes  HepB vaccine \n(unspecified) \nwithin 1 \nmonth of age \nat HMO B (Y)  (Not stratified \nby dose timing)  NR NR NR aHR: 1.03 \n(95%CI 0.60 -\n1.74)  Stratified \nby HMO, \nyear of \nbirth, and \nsex, and \nadjusted \nfor birth \nweight  \nand clinic  No \nconcerns   \nVerstraeten  \n200319 Cohort  Sleep \ndisorders   ICD-9 codes  HepB vaccine \n(unspecified) \nwithin 1 \nmonth of age \nat HMO A (Y)  (Not stratified \nby dose timing)  NR NR NR aHR: 0.79 \n(95%CI 0.38 -\n1.61)  Stratified \nby HMO, \nyear of \nbirth, and \nsex, and \nadjusted No \nconcerns   \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 57 of 84 \n Study  Study \nType  Outcome  or \nCase  Outcome \nIdentification  Intervention \nor Exposure \n(Thimerosal \nY/N/NR)  Intervention \nor Exposure % \n(n/N)  Control  \n(Thimerosal \nY/N/NR)  Control % (n/N)  p-value  Measure of \nAssociation  Adjusted  Risk of \nBias \nfor birth \nweight  \nVerstraeten  \n200319 Cohort  Sleep \ndisorders   ICD-9 codes  HepB vaccine \n(unspecified) \nwithin 1 \nmonth of age \nat HMO B (Y)  (Not stratified \nby dose timing)  NR NR NR aHR: 1.24 \n(95%CI 0.80 -\n1.93)  Stratified \nby HMO, \nyear of \nbirth, and \nsex, and \nadjusted \nfor birth \nweight  \nand clinic  No \nconcerns   \nVerstraeten  \n200319 Cohort  Sleep \ndisorders   Costar codes  HepB vaccine \n(unspecified) \nwithin 1 \nmonth of age \nat HMO C (Y)  (Not stratified \nby dose timing)  NR NR NR HR: 0.97 \n(95%CI 0.79 -\n1.19)  none  No \nconcerns   \nGeier  \n201624 Cohort  Specific delays \nin \ndevelopment   ICD-9 codes  HepB vaccine \n(unspecified) \nwithin first \nmonth of life \n(Y) (828/18,637 ) No HepB \nvaccine \nwithin first \nmonth of life  (1127/31,198 ) <0.001  RR: 1.22, \n(95% CI: \n1.12 -1.33)  none  Serious \nconcerns42  \nGeier  \n201624 Cohort  Specific delays \nin \ndevelopment   ICD-9 codes  HepB vaccine \n(unspecified) \nwithin first \nmonth of life \nfor males (Y)  (567/9514 ) No HepB \nvaccine \nwithin first \nmonth of life \nfor males  (771/16,110 ) <0.001  OR: 1.23, \n(95%CI: \n1.11 -1.37)  none  Serious \nconcerns42  \nGeier  \n201624 Cohort  Specific delays \nin \ndevelopment   ICD-9 codes  HepB vaccine \n(unspecified) \nwithin first \nmonth of life \nfor females \n(Y) (261/9122 ) No HepB \nvaccine \nwithin first \nmonth of life \nfor females  (356/15,088 ) <0.0 5 OR: 1.21; \n(95% CI: \n1.03 -1.41)  none  Serious \nconcerns42  \nVerstraeten  \n200319 Cohort  Stammering   ICD-9 codes  HepB vaccine \n(unspecified) \nwithin 1 \nmonth of age \nat HMO A (Y)  (Not stratified \nby dose timing)  NR NR NR aHR: 0.89 \n(95%CI 0.40 -\n1.97)  Stratified \nby HMO, \nyear of \nbirth, and \nsex, and \nadjusted \nfor birth \nweight  No \nconcerns   \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 58 of 84 \n Study  Study \nType  Outcome  or \nCase  Outcome \nIdentification  Intervention \nor Exposure \n(Thimerosal \nY/N/NR)  Intervention \nor Exposure % \n(n/N)  Control  \n(Thimerosal \nY/N/NR)  Control % (n/N)  p-value  Measure of \nAssociation  Adjusted  Risk of \nBias \nVerstraeten  \n200319 Cohort  Stammering   ICD-9 codes  HepB vaccine \n(unspecified) \nwithin 1 \nmonth of age \nat HMO B (Y)  (Not stratified \nby dose timing)  NR NR NR aHR: 0.61 \n(95%CI 0.33 -\n1.14)  Stratified \nby HMO, \nyear of \nbirth, and \nsex, and \nadjusted \nfor birth \nweight  \nand clinic  No \nconcerns   \nVerstraeten  \n200319 Cohort  Stammering   Costar codes  HepB vaccine \n(unspecified) \nwithin 1 \nmonth of age \nat HMO C (Y)  (Not stratified \nby dose timing)  NR NR NR HR: 0.77 \n(95%CI 0.47 -\n1.26)  none  No \nconcerns   \nVerstraeten  \n200319 Cohort  Tic Disorder, \nTics  ICD-9 codes  HepB vaccine \n(unspecified) \nwithin 1 \nmonth of age \nat HMO A (Y)  (Not stratified \nby dose timing)  NR NR NR aHR: 1.25 \n(95%CI 0.47 -\n3.29)  Stratified \nby HMO, \nyear of \nbirth, and \nsex, and \nadjusted \nfor birth \nweight  No \nconcerns   \nVerstraeten  \n200319 Cohort  Tic Disorder, \nTics  ICD-9 codes  HepB vaccine \n(unspecified) \nwithin 1 \nmonth of age \nat HMO B (Y)  (Not stratified \nby dose timing)  NR NR NR aHR: 0.85 \n(95%CI 0.55 -\n1.30)  Stratified \nby HMO, \nyear of \nbirth, and \nsex, and \nadjusted \nfor birth \nweight  \nand clinic  No \nconcerns   \nVerstraeten  \n200319 Cohort  Tic Disorder, \nTics  Costar codes  HepB vaccine \n(unspecified) \nwithin 1 \nmonth of age \nat HMO C (Y)  (Not stratified \nby dose timing)  NR NR NR HR: 0.93 \n(95%CI 0.45 -\n1.92)  none  No \nconcerns   \nGeier  \n201523 Case -\ncontrol  Tic Disorder, \nTics  ICD-9 codes  HepB vaccine \n(unspecified) \n(Y) or \ncombined Exposure/Cases: \n(151/ 344) HepB vaccine \n(unspecified) \n(Y) or \ncombined Exposure/Controls: \n(9222/28016 ) <0.00001  OR: 1.59; \n(95%CI: \n1.29 -1.98)  \n(assessed as none  Serious \nConcerns43  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 59 of 84 \n Study  Study \nType  Outcome  or \nCase  Outcome \nIdentification  Intervention \nor Exposure \n(Thimerosal \nY/N/NR)  Intervention \nor Exposure % \n(n/N)  Control  \n(Thimerosal \nY/N/NR)  Control % (n/N)  p-value  Measure of \nAssociation  Adjusted  Risk of \nBias \nHib-HepB \nvaccine or no \nvaccine \nwithin first \nmonth of life \nfor cases \n(diagnosed \nwith tic \ndisorder)  Hib-HepB \nvaccine or no \nvaccine \nwithin first \nmonth of life \nfor controls \n(no diagnosis \nof tic \ndisorder)  OR of \nexposure to \nthimerisol -\ncontaining \nvaccine in \ncases v. \ncontrols)  \nGeier  \n201523 Case -\ncontrol  Tic Disorder, \nTics  ICD-9 codes  HepB vaccine \n(unspecified) \n(Y) or \ncombined \nHib-HepB \nvaccine or no \nvaccine \nwithin first \nmonth of life \nfor male \ncases \n(diagnosed \nwith tic \ndisorder)  Exposure/Cases:  \n(113/253)  HepB vaccine \n(unspecified) \n(Y) or \ncombined \nHib-HepB \nvaccine or no \nvaccine \nwithin first \nmonth of life \nfor male \ncontrols (no \ndiagnosis of \ntic disorder)  Exposure/Controls: \n(4697/ 14327)  <0.0001  OR: 1.65; \n(95%CI: \n1.29 -2.12)  \n(assessed as \nOR of \nexposure to \nthimerisol -\ncontaining \nvaccine in \ncases v. \ncontrols)  Stratified \nby sex  Serious \nConcerns43  \nGeier  \n201523 Case -\ncontrol  Tic Disorder, \nTics  ICD-9 codes  HepB vaccine \n(unspecified) \n(Y) or \ncombined \nHib-HepB \nvaccine or no \nvaccine \nwithin first \nmonth of life \nfor female \ncases \n(diagnosed \nwith tic \ndisorder)  Exposure/Cases:  \n(38/ 91) HepB vaccine \n(unspecified) \n(Y) or \ncombined \nHib-HepB \nvaccine or no \nvaccine \nwithin first \nmonth of life \nfor female \ncontrols (no \ndiagnosis of \ntic disorder)  Exposure/Controls: \n(4525/ 13689)  0.09  OR: 1.45; \n(95%CI: \n0.95 -2.21)  \n(assessed as \nOR of \nexposure to \nthimerisol -\ncontaining \nvaccine in \ncases v. \ncontrols)  Stratified \nby sex  Serious \nConcerns43  \n \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 60 of 84 \n Table 26. Neurologic Results of Studies Meeting Inclusion Criteria  \nStudy  Study \nType  Outcome  or \nCase  Outcome \nIdentification  Intervention \nor Exposure \n(Thimerosal \nY/N/NR)  Intervention \nor Exposure  \n% (n/N)  Control  \n(Thimerosal \nY/N/NR)  Control % (n/N)  p-value  Measure of \nAssociation  Adjusted  Risk of \nBias \nNiu \n199612 Case \nseries  Abnormal \nCSF (Any)  NR Hep B vaccine \n(unspecified) \ninfants aged \n<0.1 yrs of \nage (Y) 6.7% (4/60)  NR NR NR NR NR Some \nconcerns20  \nNiu \n199612 Case \nseries  Abnormal \nCSF (Serious)  NR Hep B vaccine \n(unspecified) \ninfants aged \n<0.1 yrs of \nage (Y) 6.7% (4/60)  NR NR NR NR NR Some \nconcerns20  \nGeier  \n201523 Case -\ncontrol  Cerebral \ndegeneration   ICD-9 codes  HepB vaccine \n(unspecified) \n(Y) or \ncombined \nHib-HepB \nvaccine or no \nvaccine \nwithin first \nmonth of life \nfor cases \n(diagnosed \nwith cerebral \ndegeneration)  Exposure/Cases: \n(175/ 647)  HepB vaccine \n(unspecified) \n(Y) or \ncombined \nHib-HepB \nvaccine or no \nvaccine \nwithin first \nmonth of life \nfor controls \n(no diagnosis \nof tic \ndisorder)  Exposure/Controls:  \n(62637/ 135889)  <0.00001  OR: 0.43; \n(95%CI: \n0.36 -0.52)  \n(assessed as \nOR of \nexposure to \nthimerisol -\ncontaining \nvaccine in \ncases v. \ncontrols)  none  Serious \nconcerns47  \nNiu \n199612 Case \nseries  Convulsions  \n(Any)  NR Hep B vaccine \n(unspecified) \ninfants aged \n<0.1 yrs of \nage (Y) 10% (6/60)  NR NR NR NR NR Some \nconcerns20  \nNiu \n199612 Case \nseries  Convulsions \n(Serious)  NR Hep B vaccine \n(unspecified) \ninfants aged \n<0.1 yrs of \nage (Y) 6.7% (4/60)  NR NR NR NR NR Some \nconcerns20  \nLewis  \n20016 Cohort  Seizure  ICD-9 codes, \ncomputerized \ndatabase \nsearch  Hep B vaccine \n(unspecified) \nwithin first 21 \ndays of life (Y)  (1/3302)  No Hep B \nvaccine \nwithin first (4/2353)  0.17  RR: 0.18 \n(95%CI: \n0.02 -1.6) NR No \nconcerns   \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 61 of 84 \n Study  Study \nType  Outcome  or \nCase  Outcome \nIdentification  Intervention \nor Exposure \n(Thimerosal \nY/N/NR)  Intervention \nor Exposure  \n% (n/N)  Control  \n(Thimerosal \nY/N/NR)  Control % (n/N)  p-value  Measure of \nAssociation  Adjusted  Risk of \nBias \n21 days of \nlife \nLewis  \n20016 Cohort  Seizure  ICD-9 codes, \ncomputerized \ndatabase \nsearch  Hep B vaccine \n(unspecified) \non day of \nbirth or day \nafter birth (Y) (1/2718)  No Hep B \nvaccine \nwithin first \n21 days of \nlife (4/2353)  0.19  RR: 0.22; \n(95%CI: \n0.02 -1.9) NR No \nconcerns   \nHaber  \n201816 Case \nseries  Nervous \nsystem \ndisorders   VAERS, non -\ndeath, serious \nreports  Hep B vaccine \n(unspecified) \ninfants aged \n<1 month (Y)  6.3%  (15/240 ) NR NR NR NR NR Some \nconcerns39  \nLewis  \n20016 Cohort  Neurologic \ndisease, \nother than \nseizure   computerized \ndatabase \nsearch  Hep B vaccine \n(unspecified) \nwithin first 21 \ndays of life (Y)  (4/3,302 ) No Hep B \nvaccine \nwithin first \n21 days of \nlife (2/2,353 ) 0.99  RR: 1.4 \n(95%CI: 0.3 -\n7.8) NR No \nconcerns   \nLewis  \n20016 Cohort  Neurologic \ndisease, \nother than \nseizure   computerized \ndatabase \nsearch  Hep B vaccine \n(unspecified) \non day of \nbirth or day \nafter birth (Y) (4/2,718 ) No Hep B \nvaccine \nwithin first \n21 days of \nlife (2/2,353 ) 0.69  RR: 1.7; \n(95%CI: 0.3 -\n9.4) NR No \nconcerns   \n \nTable 27. Cardiopulmonary Results of Studies Meeting Inclusion Criteria  \nStudy  Study \nType  Outcome  Outcome \nIdentification  Intervention \n(Thimerosal \nY/N/NR)  Intervention \n% (n/N)  Control  \n(Thimerosal \nY/N/NR)  Control % \n(n/N)  p-value  Measure of \nAssociation  Adjusted  Risk of \nBias \nMorgan  \n20257 Cohort  Bronchopulmonary \ndysplasia  ICD-10 \nAustralian \nmodification  \ncodes  Hep B vaccine \n(unspecified) \nwithin 24h of \nbirth  for \nextremely \npremature \ninfants (<29 \nweeks \ngestation)  \n(NR)  (155/306)  No recorded \nHep B \nvaccine \nwithin 24h of \nbirth  for \nextremely \npremature \ninfants (<29 \nweeks \ngestation)  (317/512)  NR aRR: 0.83; \n(95%CI: 0.68 -\n1.0) Maternal \nage, low \nApgar at 1 \nminute, low \nApgar at 5 \nminutes, \nmaternal \nsmoking, \ngestation \nperiod and \ncongenital No \nconcerns   \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 62 of 84 \n Study  Study \nType  Outcome  Outcome \nIdentification  Intervention \n(Thimerosal \nY/N/NR)  Intervention \n% (n/N)  Control  \n(Thimerosal \nY/N/NR)  Control % \n(n/N)  p-value  Measure of \nAssociation  Adjusted  Risk of \nBias \nheart \ndisease \nstatus  \nNiu \n199612 Case series  Apnea  (Any)  NR Hep B vaccine \n(unspecified) \ninfants aged \n<0.1 yrs of \nage (Y) 8.3% ( 5/60)  NR NR NR NR NR Some \nconcernst  \nNiu \n199612 Case series  Apnea  (Serious)  NR Hep B vaccine \n(unspecified) \ninfants aged \n<0.1 yrs of \nage (Y) (3/60)  NR NR NR NR NR Some \nconcernst  \nNiu \n199612 Case series  Bradycardia  (Any)  NR Hep B vaccine \n(unspecified) \ninfants aged \n<0.1 yrs of \nage (Y) 1.7% (1/60)  NR NR NR NR NR Some \nconcernst  \nNiu \n199612 Case series  Bradycardia  (Serious)  NR Hep B vaccine \n(unspecified) \ninfants aged \n<0.1 yrs of \nage (Y) 1.7% (1/60)  NR NR NR NR NR Some \nconcernst  \nNiu \n199612 Case series  Cyanosis  (Any)  NR Hep B vaccine \n(unspecified) \ninfants aged \n<0.1 yrs of \nage (Y) 11.7% ( 7/60)  NR NR NR NR NR Some \nconcernst  \nNiu \n199612 Case series  Cyanosis  (Serious)  NR Hep B vaccine \n(unspecified) \ninfants aged \n<0.1 yrs of \nage (Y) (5/60)  NR NR NR NR NR Some \nconcernst  \n \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 63 of 84 \n Table 28. Systemic Reactions Results of Studies Meeting Inclusion Criteria  \nStudy  Study \nType  Outcome  Outcome \nIdentification  Intervention \n(Thimerosal \nY/N/NR)  Intervention \n% (n/N)  Control  \n(Thimerosal \nY/N/NR)  Control \n% (n/N)  p-value  Measure of \nAssociation  Adjusted  Risk of \nBias \nNiu \n199612 Case \nseries  Agitation  (Any)  NR Hep B vaccine \n(unspecified) \ninfants aged \n<0.1 yrs of age  \n(Y) 21.7% (13/60)  NR NR NR NR NR Some \nconcernsq   \nNiu \n199612 Case \nseries  Agitation  (Serious)  NR Hep B vaccine \n(unspecified) \ninfants aged \n<0.1 yrs of age  \n(Y) 11.7% (7/60)  NR NR NR NR NR Some \nconcernsq   \nYerushalmi  \n19979 RCT Anorexia/Decreased \nappetite    Parental \nreport on diary \ncard for 5 days \npost -\nvaccination  Engerix -B \nvaccine within \n24 hrs of birth \n(Y) 0% (0/52)  BioHepB \nvaccine within \n24 hrs of birth \n(Y) 2.0% \n(3/153)  NR NR NR Some \nconcerns28  \nGreenberg  \n200214 RCT Anorexia/Decreased \nappetite  (Any)  Solicited \nparental \nreport for day \nof vaccination \nand 3 days \nfollowing \nvaccination  Engerix -B \nvaccine within \n4 days of birth  \n(NR)  14.0% \n(NR/136)  DTaP -HepB, \nOPV, and Hib \nvaccines at 2 \nmonths of age \n(NR)  25.6% \n(NR/129)  NR NR NR Some \nconcerns28  \nGreenberg  \n200214 RCT Anorexia/Decreased \nappetite  (Severe/Grade \n3) Solicited \nparental \nreport for day \nof vaccination \nand 3 days \nfollowing \nvaccination ; \nGrade 3 -\nprevented \nnormal daily \nactivities  Engerix -B \nvaccine within \n4 days of birth  \n(NR)  1.5% \n(NR/136)  DTaP -HepB, \nOPV, and Hib \nvaccines at 2 \nmonths of age \n(NR)  0.8% \n(NR/129)  NR NR NR Some \nconcerns28  \nWood  \n201818 RCT Feeding \nissues /Anorexia (Any)  Parental \nreport, within \n2 days of dose  Engerix -B \nvaccine given \nalone within \n120 hrs of \nbirth (Y) ; \n87.6 % 17% (17/103)  Engerix -B co-\nadministered \nwith \ninvestigational \nacellular \nPertussis 13% \n(28/221)  NR NR NR Some \nconcerns32  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 64 of 84 \n Study  Study \nType  Outcome  Outcome \nIdentification  Intervention \n(Thimerosal \nY/N/NR)  Intervention \n% (n/N)  Control  \n(Thimerosal \nY/N/NR)  Control \n% (n/N)  p-value  Measure of \nAssociation  Adjusted  Risk of \nBias \nvaccinated \ndays 0 -2 vaccine within \n120 hrs of \nbirth (Y ); 91% \nvaccinated \ndays 0-2 \nWood  \n201818 RCT Feeding \nissues /Anorexia (Grade \n3/Severe)  Parental \nreport, within \n2 days of dose; \nGrade 3 -\nprevents \nnormal \neveryday \nactivities or \nrequires \nsignificant \nmedical \nintervention  Engerix -B \nvaccine given \nalone within \n120 hrs of \nbirth (Y) ; \n87.6 % \nvaccinated \ndays 0 -2 0.9% (1/103)  Engerix -B co-\nadministered \nwith \ninvestigational \nacellular \nPertussis \nvaccine within \n120 hrs of \nbirth (Y ); 91% \nvaccinated \ndays 0-2 0 NR NR NR Some \nconcerns32  \nLopez  \n200211 Cohort  Anorexia/Decreased \nappetite  (Any)  Solicited self -\nreport by diary \ncard during 4 -\nday follow -up \nwindow  HepB Engerix -\nB at birth (Y)  2.6% (3/117)  NR NR NR NR NR Some \nconcerns54  \nLopez  \n200211 Cohort  Anorexia/Decreased \nappetite  (Severe)  Solicited self -\nreport by diary \ncard during 4 -\nday follow -up \nwindow  HepB Engerix -\nB at birth (Y)  1.7% (2/117)  NR NR NR NR NR Some \nconcerns54  \nSapru  \n200713 RCT Constipation   Parental \nreport until \ntotal follow -up \nperiod of 18 \nweeks  Engerix -B \nvaccine within \nfirst 2 weeks \nof life (NR)  0% (0/130)  GeneVacB \n(HepB) \nvaccine within \nfirst 2 weeks \nof life (NR)  0% \n(0/132)  NR NR NR No \nconcerns   \n \nWood  \n201818 RCT Diarrhea  (Any)  Parental \nreport, within \n2 days of dose  Engerix -B \nvaccine given \nalone within \n120 hrs of \nbirth (Y) ; \n87.6 % \nvaccinated \ndays 0 -2 12% (12/103)  Engerix -B co-\nadministered \nwith \ninvestigational \nacellular \nPertussis \nvaccine within \n120 hrs of \nbirth (Y ); 91% 17.0% \n(38/221)  NR NR NR Some \nconcerns25  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 65 of 84 \n Study  Study \nType  Outcome  Outcome \nIdentification  Intervention \n(Thimerosal \nY/N/NR)  Intervention \n% (n/N)  Control  \n(Thimerosal \nY/N/NR)  Control \n% (n/N)  p-value  Measure of \nAssociation  Adjusted  Risk of \nBias \nvaccinated \ndays 0-2 \nWood  \n201818 RCT Diarrhea  (Severe/Grade \n3) Parental \nreport, within \n2 days of dose ; \nGrade 3 -\nprevents \nnormal \neveryday \nactivities or \nrequires \nsignificant \nmedical \nintervention  Engerix -B \nvaccine given \nalone within \n120 hrs of \nbirth (Y) ; \n87.6 % \nvaccinated \ndays 0 -2 0 Engerix -B co-\nadministered \nwith \ninvestigational \nacellular \nPertussis \nvaccine within \n120 hrs of \nbirth (Y ); 91% \nvaccinated \ndays 0-2 0 NR NR NR Some \nconcerns25  \nSapru  \n200713 RCT Diarrhea  (loose \nmotions)  Parental \nreport until \ntotal follow -up \nperiod of 18 \nweeks  Engerix -B \nvaccine within \nfirst 2 weeks \nof life (NR)  0% (0/130)  GeneVacB \n(HepB) \nvaccine within \nfirst 2 weeks \nof life (NR)  0% \n(0/132)  NR NR NR Some \nconcerns30  \nGreenberg  \n200214 RCT Diarrhea  (Any)  Solicited \nparental \nreport for day \nof vaccination \nand 3 days \nfollowing \nvaccination  Engerix -B \nvaccine within \n4 days of birth  \n(NR)  8.1% \n(NR/136)  DTaP -HepB, \nOPV, and Hib \nvaccines at 2 \nmonths of age \n(NR)  10.1% \n(NR/129)  NR NR NR Some \nconcerns30  \nGreenberg  \n200214 RCT Diarrhea  (Severe/Grade \n3)  Solicited \nparental \nreport for day \nof vaccination \nand 3 days \nfollowing \nvaccination ; \nGrade 3 -\nprevented \nnormal daily \nactivities  Engerix -B \nvaccine within \n4 days of birth  \n(NR)  0.7% \n(NR/136)  DTaP -HepB, \nOPV, and Hib \nvaccines at 2 \nmonths of age \n(NR)  0% \n(0/129)  NR NR NR Some \nconcerns30  \nYerushalmi  \n19979 RCT Diarrhea   Parental \nreport on diary \ncard for 5 days Engerix -B \nvaccine within \n24 hrs of birth \n(Y) 0% (0/52)  BioHepB \nvaccine within \n24 hrs of birth \n(Y) 0.64% \n(1/152)  NR NR NR Some \nconcerns30  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 66 of 84 \n Study  Study \nType  Outcome  Outcome \nIdentification  Intervention \n(Thimerosal \nY/N/NR)  Intervention \n% (n/N)  Control  \n(Thimerosal \nY/N/NR)  Control \n% (n/N)  p-value  Measure of \nAssociation  Adjusted  Risk of \nBias \npost -\nvaccination  \nNiu \n199612 Case \nseries  Diarrhea  (Any)  NR Hep B vaccine \n(unspecified) \ninfants aged \n<0.1 yrs of age  \n(Y) 1.7% (1/60)  NR NR NR NR NR Some \nconcerns24  \nNiu \n199612 Case \nseries  Diarrhea  (Serious)  NR Hep B vaccine \n(unspecified) \ninfants aged \n<0.1 yrs of age  \n(Y) 1.7% (1/60)  NR NR NR NR NR Some \nconcerns24  \nGreenberg  \n200214 RCT Drowsiness or sleeping \nmore  (Any)  Solicited \nparental \nreport for day \nof vaccination \nand 3 days \nfollowing \nvaccination  Engerix -B \nvaccine within \n4 days of birth  \n(NR)  32.4% \n(NR/136)  DTaP -HepB, \nOPV, and Hib \nvaccines at 2 \nmonths of age \n(NR)  40.3% \n(NR/129)  NR NR NR Some \nconcerns31  \nGreenberg  \n200214 RCT Drowsiness or sleeping \nmore  (Severe/Grade 3)  Solicited \nparental \nreport for day \nof vaccination \nand 3 days \nfollowing \nvaccination ; \nGrade 3 -\nprevented \nnormal daily \nactivities  Engerix -B \nvaccine within \n4 days of birth  \n(NR)  2.9% \n(NR/136)  DTaP -HepB, \nOPV, and Hib \nvaccines at 2 \nmonths of age \n(NR)  0.8% \n(NR/129)  NR NR NR Some \nconcerns31  \nWood  \n201818 RCT Drowsiness or sleeping \nmore  (Any)  Parental \nreport, within \n2 days of dose  Engerix -B \nvaccine given \nalone within \n120 hrs of \nbirth (Y) ; \n87.6 % \nvaccinated \ndays 0 -2 28% (28/103)  Engerix -B co-\nadministered \nwith \ninvestigational \nacellular \nPertussis \nvaccine within \n120 hrs of \nbirth (Y ); 91% \nvaccinated \ndays 0-2 18% \n(39/221)  NR NR NR Some \nconcerns29  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 67 of 84 \n Study  Study \nType  Outcome  Outcome \nIdentification  Intervention \n(Thimerosal \nY/N/NR)  Intervention \n% (n/N)  Control  \n(Thimerosal \nY/N/NR)  Control \n% (n/N)  p-value  Measure of \nAssociation  Adjusted  Risk of \nBias \nWood  \n201818 RCT Drowsiness or sleeping \nmore  (Severe/Grade 3)  Parental \nreport, within \n2 days of dose; \nGrade 3 -\nprevents \nnormal \neveryday \nactivities or \nrequires \nsignificant \nmedical \nintervention  Engerix -B \nvaccine given \nalone within \n120 hrs of \nbirth (Y) ; \n87.6 % \nvaccinated \ndays 0 -2 0.9% (1/ 103) Engerix -B co-\nadministered \nwith \ninvestigational \nacellular \nPertussis \nvaccine within \n120 hrs of \nbirth (Y ); 91% \nvaccinated \ndays 0-2 0.5% \n(1/221) NR NR NR Some \nconcerns29  \nLopez11 \n2002  Cohort  Drowsiness or sleeping \nmore  (Any)  Solicited self -\nreport by diary \ncard during 4 -\nday follow -up \nwindow  HepB Engerix -\nB at birth (Y)  5.1% (6/117)  NR NR NR NR NR Some \nconcerns26  \nLopez  \n200211 Cohort  Drowsiness or sleeping \nmore  (Severe)  Solicited self -\nreport by diary \ncard during 4 -\nday follow -up \nwindow  HepB Engerix -\nB at birth (Y)  0.9% (1/117)  NR NR NR NR NR Some \nconcerns26  \nLinder  \n199910 Cohort  Fever  (neonatal fever \n>37.5 ⁰C) Birth \nhospitalization \ndischarge \ndiagnosis  HepB vaccine \n(unspecified) \non first day of \nlife (NR)  1.2% \n(68/5819)  No HepB \nvaccine on \nfirst day of life  0.54% \n(27/5010)  0.001  NR NR Serious \nconcerns34  \nLinder  \n199910 Cohort  Fever  (neonatal fever \n>38⁰C) Birth \nhospitalization \ndischarge \ndiagnosis  HepB vaccine \n(unspecified) \non first day of \nlife (NR)  0.9% \n(50/5819)  No HepB \nvaccine on \nfirst day of life  0.54% \n(27/5010)  0.05 NR NR Serious \nconcerns34  \nLinder  \n199910 Cohort  Fever  (explained \nneonatal fever)  Birth \nhospitalization \ndischarge \ndiagnosis  HepB vaccine \n(unspecified) \non first day of \nlife (NR)  0.3% \n(15/5819)  No HepB \nvaccine on \nfirst day of life  0.3% \n(13/5010)  NR NR NR Serious \nconcerns34  \nLinder  \n199910 Cohort  Fever  (unexplained \nneonatal fever)  Birth \nhospitalization \ndischarge \ndiagnosis  HepB vaccine \n(unspecified) \non first day of \nlife (NR)  0.6% \n(35/5819)  No HepB \nvaccine on \nfirst day of life  0.3% \n(14/5010)  0.013  NR NR Serious \nconcerns34  \nLopez  \n200211 Cohort  Fever  (Any)  Solicited self -\nreport by diary \ncard during 4 -HepB Engerix -\nB at birth (Y)  0.9% (1/117)  NR NR NR NR NR Some \nconcerns \n28  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 68 of 84 \n Study  Study \nType  Outcome  Outcome \nIdentification  Intervention \n(Thimerosal \nY/N/NR)  Intervention \n% (n/N)  Control  \n(Thimerosal \nY/N/NR)  Control \n% (n/N)  p-value  Measure of \nAssociation  Adjusted  Risk of \nBias \nday follow -up \nwindow  \nLopez  \n200211 Cohort  Fever  (Severe)  Solicited self -\nreport by diary \ncard during 4 -\nday follow -up \nwindow ; \nsevere >39 \naxillary or \n>39.5 rectal  HepB Engerix -\nB at birth (Y)  0.9% (1/117)  NR NR NR NR NR Some \nconcerns \n28  \nNiu \n199612 Case \nseries  Fever  (Any)  NR Hep B vaccine \n(unspecified) \ninfants aged \n<0.1 yrs of age  \n(Y) 30% (18/60)  NR NR NR NR NR Some \nconcerns24  \nNiu \n199612 Case \nseries  Fever (Serious)  NR Hep B vaccine \n(unspecified) \ninfants aged \n<0.1 yrs of age  \n(Y) 21.7% (13/60)  NR NR NR NR NR Some \nconcerns24  \nBassily  \n19958 RCT Fever  Parental \nreport of 1-2 \ndays of fever \n≤102⁰F  Recombivax \nimmediately \nafter birth (Y)  5.6% \n(NR/178)  Recombivax \nat 18 months \nof age (Y)  2.1% \n(NR/191)  NR NR NR Some \nconcerns \n33  \nBassily  \n19958 RCT Fever  Parental \nreport of 1 -2 \ndays of fever \n≤102⁰F  Recombivax \nat 2 months of \nage (Y)  7.2% \n(NR/167)  Recombivax \nat 18 months \nof age (Y)  2.1% \n(NR/191)  NR NR NR Some \nconcerns \n33  \nYerushalmi  \n19979 RCT Fever  (≥38⁰C ) Parental \nreport on diary \ncard for 5 d ays \npost -\nvaccination  Engerix -B \nvaccine within \n24 hrs of birth \n(Y) 0% (0/52)  BioHepB \nvaccine within \n24 hrs of birth \n(Y) 1.3% \n(2/153)  NR NR NR Some \nconcerns \n59  \nGreenberg  \n200214 RCT Fever  (Any )  Solicited \nparental \nreport for day \nof vaccination \nand 3 days \nfollowing \nvaccination ; \nRectal Engerix -B \nvaccine within \n4 days of birth  \n(NR)  5.9% \n(NR/136)  DTaP -HepB, \nOPV, and Hib \nvaccines at 2 \nmonths of age \n(NR)  14.7% \n(NR/129)  NR NR NR Some \nconcerns \n59  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 69 of 84 \n Study  Study \nType  Outcome  Outcome \nIdentification  Intervention \n(Thimerosal \nY/N/NR)  Intervention \n% (n/N)  Control  \n(Thimerosal \nY/N/NR)  Control \n% (n/N)  p-value  Measure of \nAssociation  Adjusted  Risk of \nBias \ntemperature \n≥38⁰C  \nGreenberg  \n200214 RCT Fever  (Severe/Grade 3)  Solicited \nparental \nreport for day \nof vaccination \nand 3 days \nfollowing \nvaccination ; \nGrade 3 -fever \n>39.5 ⁰C Engerix -B \nvaccine within \n4 days of birth  \n(NR)  0% (0/136)  DTaP -HepB, \nOPV, and Hib \nvaccines at 2 \nmonths of age \n(NR)  0.8% \n(NR/129)  NR NR NR Some \nconcerns \n59  \nSapru  \n200713 RCT Fever (axillary \ntemperature ≥38⁰C ) Parental \nreport until \ntotal follow -up \nperiod of 18 \nweeks  Engerix -B \nvaccine within \nfirst 2 weeks \nof life (NR)  4.6% (6/130)  GeneVacB \n(HepB) \nvaccine within \nfirst 2 weeks \nof life (NR)  3.0% \n(4/132)  NR NR NR Some \nconcerns \n59  \nWood  \n201818 RCT Fever  (≥38⁰C ) Parental \nreport, within \n2 days of dose  Engerix -B \nvaccine given \nalone within \n120 hrs of \nbirth (Y) ; \n87.6 % \nvaccinated \ndays 0 -2 0.7% (1/138)  Engerix -B co-\nadministered \nwith \ninvestigational \nacellular \nPertussis \nvaccine within \n120 hrs of \nbirth (Y ); 91% \nvaccinated \ndays 0-2 0 NR NR NR Some \nconcerns \n59  \nWood  \n201818 RCT Fever ( ≥39⁰C) Parental \nrepo rt, within \n2 days of dose  Engerix -B \nvaccine given \nalone within \n120 hrs of \nbirth (Y) ; \n87.6 % \nvaccinated \ndays 0 -2 0 Engerix -B co-\nadministered \nwith \ninvestigational \nacellular \nPertussis \nvaccine within \n120 hrs of \nbirth (Y ); 91% \nvaccinated \ndays 0-2 0 NR NR NR Some \nconcerns \n59  \nWood  \n201818 RCT Irritability or \nfussiness  (Any)  Parental \nreport, within \n2 days of dose  Engerix -B \nvaccine given \nalone within 20% (21/103)  Engerix -B co-\nadministered \nwith 24.0% \n(54/221)  NR NR NR Serious \nconcerns34  \n \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 70 of 84 \n Study  Study \nType  Outcome  Outcome \nIdentification  Intervention \n(Thimerosal \nY/N/NR)  Intervention \n% (n/N)  Control  \n(Thimerosal \nY/N/NR)  Control \n% (n/N)  p-value  Measure of \nAssociation  Adjusted  Risk of \nBias \n120 hrs of \nbirth (Y) ; \n87.6 % \nvaccinated \ndays 0 -2 investigational \nacellular \nPertussis \nvaccine within \n120 hrs of \nbirth (Y ); 91% \nvaccinated \ndays 0-2 \nWood  \n201818 RCT Irritability or fussiness  \n(Severe/Grade 3)   Parental \nreport, within \n2 days of dose; \nGrade 3 -\nprevents \nnormal \neveryday \nactivities or \nrequires \nsignificant \nmedical \nintervention  Engerix -B \nvaccine given \nalone within \n120 hrs of \nbirth (Y) ; \n87.6 % \nvaccinated \ndays 0 -2 0.9% ( 1/103 ) Engerix -B co-\nadministered \nwith \ninvestigational \nacellular \nPertussis \nvaccine within \n120 hrs of \nbirth (Y ); 91% \nvaccinated \ndays 0-2 0.9% \n(2/221 ) NR NR NR Serious \nconcerns34  \n \nGreenberg  \n200214 RCT Irritability or \nfussiness  (Any)  Solicited \nparental \nreport for day \nof vaccination \nand 3 days \nfollowing \nvaccination  Engerix -B \nvaccine within \n4 days of birth  \n(NR)  22.1% \n(NR/136)  DTaP -HepB, \nOPV, and Hib \nvaccines at 2 \nmonths of age \n(NR)  54.3% \n(NR/129)  NR NR NR Serious \nconcerns34  \nGreenberg  \n200214 RCT Irritability or \nfussiness  (Severe/Grade \n3) Solicited \nparental \nreport for day \nof vaccination \nand 3 days \nfollowing \nvaccination ; \nGrade 3 -\nprevented \nnormal daily \nactivities  Engerix -B \nvaccine within \n4 days of birth  \n(NR)  0.7% \n(NR/136)  DTaP -HepB, \nOPV, and Hib \nvaccines at 2 \nmonths of age \n(NR)  3.9% \n(NR/129)  NR NR NR Serious \nconcerns34  \nYerushalmi  \n19979 RCT Irritability or fussiness   Parental \nreport on diary \ncard for 5 days Engerix -B \nvaccine within 11.5% (6/52)  BioHepB \nvaccine within 3.3% \n(5/153)  NR NR NR Serious \nconcerns34  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 71 of 84 \n Study  Study \nType  Outcome  Outcome \nIdentification  Intervention \n(Thimerosal \nY/N/NR)  Intervention \n% (n/N)  Control  \n(Thimerosal \nY/N/NR)  Control \n% (n/N)  p-value  Measure of \nAssociation  Adjusted  Risk of \nBias \npost -\nvaccination  24 hrs of birth \n(Y) 24 hrs of birth \n(Y) \nLopez  \n200211 Cohort  Irritability or \nfussiness  (Any)  Solicited self -\nreport by diary \ncard during 4 -\nday follow -up \nwindow  HepB Engerix -\nB at birth (Y)  2.6% (3/117)  NR NR NR NR NR Some \nconcerns65  \nLopez  \n200211 Cohort  Irritability or \nfussiness  (Severe)  Solicited self -\nreport by diary \ncard during 4 -\nday follow -up \nwindow  HepB Engerix -\nB at birth (Y)  1.7% (2/117)  NR NR NR NR NR Some \nconcerns65  \nSapru  \n200713 RCT Rash  Parental \nreport until \ntotal follow -up \nperiod of 18 \nweeks  Engerix -B \nvaccine within \nfirst 2 weeks \nof life (NR)  0% (0/130)  GeneVacB \n(HepB) \nvaccine within \nfirst 2 weeks \nof life (NR)  0% \n(0/132)  NR NR NR No \nConcerns   \nNiu \n199612 Case \nseries  Rash  (Any)  NR Hep B vaccine \n(unspecified) \ninfants aged \n<0.1 yrs of age  \n(Y) 3.3% (2/60)  NR NR NR NR NR Some \nconcerns31  \n \nNiu \n199612 Case \nseries  Rash (Serious)  NR Hep B vaccine \n(unspecified) \ninfants aged \n<0.1 yrs of age  \n(Y) 3.3% (2/60)  NR NR NR NR NR Some \nconcerns31  \n \nWood  \n201818 RCT Restlessness or sleeping \nless (Any)  Parental \nreport, within \n2 days of dose  Engerix -B \nvaccine given \nalone within \n120 hrs of \nbirth (Y) ; \n87.6 % \nvaccinated \ndays 0 -2 31% (32/103)  Engerix -B co-\nadministered \nwith \ninvestigational \nacellular \nPertussis \nvaccine within \n120 hrs of \nbirth (Y ); 91% \nvaccinated \ndays 0-2 22.0% \n(49/221)  NR NR NR Serious \nconcerns38  \nWood  \n201818 RCT Restlessness or sleeping \nless (Severe/Grade 3)  Parental \nreport, within \n2 days of dose; Engerix -B \nvaccine given \nalone within 3% (3/103)  Engerix -B co-\nadministered \nwith 1% \n(2/221)  NR NR NR Serious \nconcerns38  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 72 of 84 \n Study  Study \nType  Outcome  Outcome \nIdentification  Intervention \n(Thimerosal \nY/N/NR)  Intervention \n% (n/N)  Control  \n(Thimerosal \nY/N/NR)  Control \n% (n/N)  p-value  Measure of \nAssociation  Adjusted  Risk of \nBias \nGrade 3 -\nprevents \nnormal \neveryday \nactivities or \nrequires \nsignificant \nmedical \nintervention  120 hrs of \nbirth (Y) ; \n87.6 % \nvaccinated \ndays 0 -2 investigational \nacellular \nPertussis \nvaccine within \n120 hrs of \nbirth (Y ); 91% \nvaccinated \ndays 0-2 \nGreenberg  \n200214 RCT Restlessness or sleeping \nless (Any)  Solicited \nparental \nreport for day \nof vaccination \nand 3 days \nfollowing \nvaccination  Engerix -B \nvaccine within \n4 days of birth  \n(NR)  16.9% \n(NR/136)  DTaP -HepB, \nOPV, and Hib \nvaccines at 2 \nmonths of age \n(NR)  26.4% \n(NR/129)  NR NR NR Serious \nconcerns38  \nGreenberg  \n200214 RCT Restlessness or sleeping \nless (Severe/Grade 3)  Solicited \nparental \nreport for day \nof vaccination \nand 3 days \nfollowing \nvaccination; \nGrade 3 -\nprevented \nnormal daily \nactivities  Engerix -B \nvaccine within \n4 days of birth  \n(NR)  1.5% \n(NR/136)  DTaP -HepB, \nOPV, and Hib \nvaccines at 2 \nmonths of age \n(NR)  0.8% \n(NR/129)  NR NR NR Serious \nconcerns38  \nGreenberg  \n200214 RCT Unusual crying  (Any)  Solicited \nparental \nreport for day \nof vaccination \nand 3 days \nfollowing \nvaccination  Engerix -B \nvaccine within \n4 days of birth  \n(NR)  1.5% \n(NR/136)  DTaP -HepB, \nOPV, and Hib \nvaccines at 2 \nmonths of age \n(NR)  3.1% \n(NR/129)  NR NR NR Some \nconcerns40  \nGreenberg  \n200214 RCT Unusual \ncrying  (Severe/Grade 3)  Solicited \nparental \nreport for day \nof vaccination \nand 3 days \nfollowing \nvaccination; Engerix -B \nvaccine within \n4 days of birth  \n(NR)  0% (0/136)  DTaP -HepB, \nOPV, and Hib \nvaccines at 2 \nmonths of age \n(NR)  0.8% \n(NR/129)  NR NR NR Some \nconcerns40  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 73 of 84 \n Study  Study \nType  Outcome  Outcome \nIdentification  Intervention \n(Thimerosal \nY/N/NR)  Intervention \n% (n/N)  Control  \n(Thimerosal \nY/N/NR)  Control \n% (n/N)  p-value  Measure of \nAssociation  Adjusted  Risk of \nBias \nGrade 3 -\nprevented \nnormal daily \nactivities  \nWood  \n201818 RCT Vomiting  (Any)  Parental \nreport, within \n2 days of dose  Engerix -B \nvaccine given \nalone within \n120 hrs of \nbirth (Y) ; \n87.6 % \nvaccinated \ndays 0 -2 24% (23/103)  Engerix -B co-\nadministered \nwith \ninvestigational \nacellular \nPertussis \nvaccine within \n120 hrs of \nbirth (Y ); 91% \nvaccinated \ndays 0 -2 20.0% \n(45/221)  NR NR NR Some \nconcerns41  \nWood  \n201818 RCT Vomiting \n(Severe/Grade 3)  Parental \nreport, within \n2 days of dose ; \nGrade 3 -\nprevents \nnormal \neveryday \nactivities or \nrequires \nsignificant \nmedical \nintervention  Engerix -B \nvaccine given \nalone within \n120 hrs of \nbirth (Y) ; \n87.6 % \nvaccinated \ndays 0 -2 0 Engerix -B co-\nadministered \nwith \ninvestigational \nacellular \nPertussis \nvaccine within \n120 hrs of \nbirth (Y) ; 91% \nvaccinated \ndays 0 -2 0 NR NR NR Some \nconcerns41  \nSapru  \n200713 RCT Vomiting  Parental \nreport until \ntotal follow -up \nperiod of 18 \nweeks  Engerix -B \nvaccine within \nfirst 2 weeks \nof life (NR)  0% (0/130)  GeneVacB \n(HepB) \nvaccine within \nfirst 2 weeks \nof life (NR)  0% \n(0/132)  NR NR NR Some \nconcerns41  \nGreenberg  \n200214 RCT Vomiting  (Any)  Solicited \nparental \nreport for day \nof vaccination \nand 3 days \nfollowing \nvaccination  Engerix -B \nvaccine within \n4 days of birth  \n(NR)  4.4% \n(NR/136)  DTaP -HepB, \nOPV, and Hib \nvaccines at 2 \nmonths of age \n(NR)  7.8% \n(NR/129)  NR NR NR Some \nconcerns41  \nGreenberg  \n200214 RCT Vomiting \n(Severe/Grade 3)  Solicited \nparental Engerix -B \nvaccine within 0% (0/136)  DTaP -HepB, \nOPV, and Hib 0% \n(0/129)  NR NR NR Some \nconcerns41  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 74 of 84 \n Study  Study \nType  Outcome  Outcome \nIdentification  Intervention \n(Thimerosal \nY/N/NR)  Intervention \n% (n/N)  Control  \n(Thimerosal \nY/N/NR)  Control \n% (n/N)  p-value  Measure of \nAssociation  Adjusted  Risk of \nBias \nreport for day \nof vaccination \nand 3 days \nfollowing \nvaccination; \nGrade 3 -\nprevented \nnormal daily \nactivities  4 days of birth  \n(NR)  vaccines at 2 \nmonths of age \n(NR)  \n \nTable 29. Other Reactions Results of Studies Meeting Inclusion Criteria  \nStudy  Study \nType  Outcome  or Case  Outcome \nIdentification  Intervention \nor Exposure \n(Thimerosal \nY/N/NR)  Intervention or \nExposure  % \n(n/N)  Control  \n(Thimerosal \nY/N/NR)  Control % (n/N)  p-value  Measure of \nAssociation  Adjusted  Risk of \nBias \nGeier  \n201825 Case -\ncontrol  Premature puberty   ICD-9 codes  HepB vaccine \n(unspecified) \n(Y) or \ncombined \nHib-HepB \nvaccine or no \nvaccine \nwithin first \nmonth of life \nfor cases \n(diagnosed \nwith \npremature \npuberty ) Exposure/Cases: \n(255/486)  HepB vaccine \n(unspecified) \n(Y) or \ncombined \nHib-HepB \nvaccine or no \nvaccine \nwithin first \nmonth of life \nfor controls \n(no \npremature \npuberty ) Exposure/Controls: \n(20582/54199)  <0.00001  OR: 1.80, \n(95% CI: \n1.51 -2.16)  \n(assessed as \nOR of \nexposure to \nthimerisol -\ncontaining \nvaccine in \ncases v. \ncontrols)  none  Serious \nconcerns67  \nGeier  \n201825 Case -\ncontrol  Premature puberty   ICD-9 codes  HepB vaccine \n(unspecified) \n(Y) or \ncombined \nHib-HepB \nvaccine or no \nvaccine \nwithin first \nmonth of life Exposure/Controls: \n(10/28)  HepB vaccine \n(unspecified) \n(Y) or \ncombined \nHib-HepB \nvaccine or no \nvaccine \nwithin first \nmonth of life Exposure/Controls: \n(10584/ 27989)  >0.99  OR: 0.91, \n(95% CI: \n0.42-1.98) \n(assessed as \nOR of \nexposure to \nthimerisol -\ncontaining \nvaccine in Stratified \nby sex  Serious \nconcerns67  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 75 of 84 \n Study  Study \nType  Outcome  or Case  Outcome \nIdentification  Intervention \nor Exposure \n(Thimerosal \nY/N/NR)  Intervention or \nExposure  % \n(n/N)  Control  \n(Thimerosal \nY/N/NR)  Control % (n/N)  p-value  Measure of \nAssociation  Adjusted  Risk of \nBias \nfor male \ncases \n(diagnosed \nwith \npremature \npuberty)  for male \ncontrols (no \npremature \npuberty)  cases v. \ncontrols)  \nGeier  \n201825 Case -\ncontrol  Premature puberty   ICD-9 codes  HepB vaccine \n(unspecified) \n(Y) or \ncombined \nHib-HepB \nvaccine or no \nvaccine \nwithin first \nmonth of life \nfor female \ncases \n(diagnosed \nwith \npremature \npuberty)  Exposure/Controls: \n(245/ 458)  \n HepB vaccine \n(unspecified) \n(Y) or \ncombined \nHib-HepB \nvaccine or no \nvaccine \nwithin first \nmonth of life \nfor female \ncontrols (no \npremature \npuberty)  Exposure/Controls: \n(9997/26209)  <0.00001  OR: 1.87, \n(95% CI: \n1.55 -2.25 ) \n(assessed as \nOR of \nexposure to \nthimerisol -\ncontaining \nvaccine in \ncases v. \ncontrols)  Stratified \nby sex  Serious \nconcerns67  \nHaber  \n201816 Case \nseries  General disorders \nand administration \nsite conditions   VAERS, non -\ndeath, serious \nreports  Hep B vaccine \n(unspecified) \ninfants aged \n<1 month (Y)  4.2% (10/240)  NR NR NR NR NR Some \nconcerns39  \nNiu \n199612 Case \nseries  Hyperbilirubenemia \n/HbSAg+   NR Hep B vaccine \n(unspecified) \ninfants aged \n<0.1 yrs of \nage (Y) 1.7% (1/60)  NR NR NR NR NR Some \nconcernsh  \nC.3. Risk of Bias Assessments for All Included Studies  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 76 of 84 \n Figure 2. Risk of Bias Assessments for Randomized Controlled Trials  \n \n Legend: Green = Yes or Possibly Yes , Yellow = Unclear , Red = No or Possibly No, Grey or Black = Not applicable   \n \n \n\n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 77 of 84 \n Figure 3. Risk of Bias Assessments for Cohort Studies  \n \n Legend: Green = Yes or Possibly Yes, Yellow = Unclear, Red = No or Possibly No, Grey or Black = Not applicable  \n \n \n \n \n \n\n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 78 of 84 \n Figure 4. Risk of Bias Assessments for Case Control Studies  \n \n Legend: Green = Yes or Possibly Yes, Yellow = Unclear, Red = No or Possibly No, Grey or Black = Not applicable  \n\n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 79 of 84 \n Figure 5. Risk of Bias Assessments for Case Series Studies  \n \n Legend: Green = Yes or Possibly Yes, Yellow = Unclear, Red = No or Possibly No, Grey or Black = Not applicable  \n  \n\n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 80 of 84 \n D. Search Strategies  \nTable 30. Searc h Strategies  and Results   \nDATABASE  STRATEGY  RUN DATE  RECORD \nCOUNT  \nMedline  \n(OVID)  \n1946 - 1. exp Hepatitis B Vaccines/  \n2. (((Hepatitis B OR HepB OR Hep B OR HBV) ADJ5 vaccin*) OR HepB -BD OR Engerix -B OR Recombivax HB).ti,ab,kf.  \n3. 1 OR 2  \n4. Exp Infant/  \n5. (Infant* OR newborn* OR new born* OR neonat* OR birth OR birth -dose*).ti,ab,kf.  \n6. 4 OR 5  \n7. Exp Safety/ OR exp Treatment Outcome/  \n8. (safety OR (vaccin* ADJ2 safe*) OR treatment outcome* OR adverse* OR harm OR harmful OR harms OR side effect* OR \nreaction*).ti,ab,kf. OR ae.fs  \n9. 7 OR 8  \n10. Exp Clinical Study/ OR exp Product Surveillance, Postmarketing/  \n11. (trial* OR observational stud* OR observation stud* OR clinical stud* OR surveillance OR reporting system* OR VAERS OR \npostmarket* OR post -market*).ti,ab,kf,hw.  \n12. 10 OR 11  \n13. 3 AND 6 AND 9 AND 12  07/31/2025  599 \nEmbase  \n(OVID)  \n1947 - 1. exp Hepatitis B Vaccine/  \n2. (((Hepatitis B OR HepB OR Hep B OR HBV) ADJ5 vaccin*) OR HepB -BD OR Engerix -B OR Recombivax HB).ti,ab,kf.  \n3. 1 OR 2  \n4. Exp Infant/  \n5. (Infant* OR newborn* OR new born* OR neonat* OR birth OR birth -dose*).ti,ab,kf.  \n6. 4 OR 5  \n7. Exp Safety/ OR exp Treatment Outcome/ OR adverse drug reaction/  \n8. (safety OR (vaccin* ADJ2 safe*) OR treatment outcome* OR adverse* OR harm OR harmful OR harms OR side effect* OR \nreaction*).ti,ab,kf. OR ae.fs  \n9. 7 OR 8  \n10. Exp Clinical Study/ OR exp Postmarketing Surveillance/  \n11. (trial* OR observational stud* OR observation stud* OR clinical stud* OR surveillance OR reporting system* OR VAERS OR \npostmarket* OR post -market*).ti,ab,kf,hw.  \n12. 10 OR 11  \n13. 3 AND 6 AND 9 AND 12  \n14. limit 13 to \"pubmed/medline\"  \n15. 13 NOT 14  \n16. limit 15 to conference abstract status  \n17. 15 NOT 16  07/31/2025  1527  \n \n- \nDUPLICATES  \n \n=165  \nUNIQUE \nRECORDS  \nCochrane \nLibrary  \n #1 [mh \"Hepatitis B Vaccines\"]  07/31/2025  400 \n \n- \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 81 of 84 \n DATABASE  STRATEGY  RUN DATE  RECORD \nCOUNT  \n#2 (((\"Hepatitis B\":ti,ab,kw OR HepB:ti,ab,kw OR \"Hep B\":ti,ab,kw OR HBV:ti,ab,kw) NEAR/5 vaccin*:ti,ab,kw) OR HepB -\nBD:ti,ab,kw OR Engerix -B:ti,ab,kw OR \"Recombivax HB\":ti,ab,kw)  \n#3 #1 OR #2  \n#4 [mh Infant]  \n#5 (Infant*:ti,ab,kw OR newborn*:ti,ab,kw OR (\"new\" NEXT born*):ti,ab,kw OR neonat*:ti,ab,kw OR birth:ti,ab,kw OR birth -\ndose*:ti,ab,kw)  \n#6 #4 OR #5  \n#7 [mh Safety] OR [mh \"Treatment Outcome\"]  \n#8 (safety:ti,ab,kw OR (vaccin*:ti,ab,kw NEAR/2 safe*:ti,ab,kw) OR (\"treatment\" NEXT outcome*):ti,ab,kw OR \nadverse*:ti,ab,kw OR harm:ti,ab,kw OR harmful:ti,ab,kw OR harms:ti,ab,kw OR (\"side\" NEXT effect*):ti,ab,kw)  \n#9 #7 OR #8  \n#10 [mh ^\"Clinical Study\"] OR [mh ^\"Product Surveillance, Postmarketing\"]  \n#11 (trial*:ti,ab,kw OR (\"observational\" NEXT stud*):ti,ab,kw OR (\"observation\" NEXT stud*):ti,ab,kw OR (\"clinical\" NEXT \nstud*):ti,ab,kw OR surveillance:ti,ab,kw OR (\"reporting\" NEXT system*):ti,ab,kw OR VAERS:ti,ab,kw OR \npostmarket*:ti,ab,kw OR post -market*:t i,ab,kw)  \n#12 #10 OR #11  \n#13 #3 AND #6 AND #9 AND #12  DUPLICATES  \n \n=145  \nUNIQUE \nRECORDS  \nCINAHL  \n(EBSCOHost)  S1 (MH \"Hepatitis B Vaccines+\")  \nS2 ((((TI \"Hepatitis B\" OR AB \"Hepatitis B\" OR SU \"Hepatitis B\") OR (TI HepB OR AB HepB OR SU HepB) OR (TI \"Hep B\" OR AB \n\"Hep B\" OR SU \"Hep B\") OR (TI HBV OR AB HBV OR SU HBV)) N5 (TI vaccin* OR AB vaccin* OR SU vaccin*)) OR (TI HepB -BD \nOR AB HepB -BD OR SU He pB-BD) OR (TI Engerix -B OR AB Engerix -B OR SU Engerix -B) OR (TI \"Recombivax HB\" OR AB \n\"Recombivax HB\" OR SU \"Recombivax HB\"))  \nS3 S1 OR S2  \nS4 (MH Infant+)  \nS5 ((TI Infant* OR AB Infant* OR SU Infant*) OR (TI newborn* OR AB newborn* OR SU newborn*) OR (TI \"new born*\" OR AB \n\"new born*\" OR SU \"new born*\") OR (TI neonat* OR AB neonat* OR SU neonat*) OR (TI birth OR AB birth OR SU birth) OR \n(TI birth -dose* OR AB birt h-dose* OR SU birth -dose*))  \nS6 S4 OR S5  \nS7 (MH Safety+) OR (MH \"Treatment Outcomes+\") OR (MH \"Adverse Drug Event+\")  \nS8 ((TI safety OR AB safety OR SU safety) OR ((TI vaccin* OR AB vaccin* OR SU vaccin*) N2 (TI safe* OR AB safe* OR SU safe*)) \nOR (TI \"treatment outcome*\" OR AB \"treatment outcome*\" OR SU \"treatment outcome*\") OR (TI adverse* OR AB \nadverse* OR SU adverse*) OR (TI harm OR AB harm OR SU harm) OR (TI harmful OR AB harmful OR SU harmful) OR (TI \nharms OR AB harms OR SU harms) OR (TI \"side effect*\" OR AB \"side effect*\" OR SU \"side effect*\"))  \nS9 S7 OR S8  \nS10 (MH \"Clinical Study+\") OR (MH \"Product Surveillance, Postmarketing+\")  \nS11 ((TI trial* OR AB trial* OR SU trial*) OR (TI \"observational stud*\" OR AB \"observational stud*\" OR SU \"observational stud*\") \nOR (TI \"observation stud*\" OR AB \"observation stud*\" OR SU \"observation stud*\") OR (TI \"clinical stud*\" OR AB \"clinical \nstud*\" OR S U \"clinical stud*\") OR (TI surveillance OR AB surveillance OR SU surveillance) OR (TI \"reporting system*\" OR AB \n\"reporting system*\" OR SU \"reporting system*\") OR (TI VAERS OR AB VAERS OR SU VAERS) OR (TI postmarket* OR AB \npostmarket* OR SU postmarket*) OR (TI post -market* OR AB post -market* OR SU post -market*))  \nS12 S10 OR S11  07/31/2025  22 \n \n- \nDUPLICATES  \n \n=7 \nUNIQUE \nRECORDS  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 82 of 84 \n DATABASE  STRATEGY  RUN DATE  RECORD \nCOUNT  \nS13 S3 AND S6 AND S9 AND S12  \n \nLimiters  - Exclude  MEDLINE  records  \n \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not \nbe construed to represent any agency determination or policy .  Page 83 of 84 \n E. References  \n \n1. Hosseini M -S, Jahanshahlou F, Akbarzadeh MA, Zarei M, Vaez -Gharamaleki Y. Formulating research questions for \nevidence -based studies. Journal of Medicine, Surgery, and Public Health . 2024/04/01/ 2024;2:100046. \ndoi:https://doi.org/10.1016/j.glmedi.2023.100046  \n2. Wells GA, Wells G, Shea B, et al. The Newcastle -Ottawa Scale (NOS) for Assessing the Quality of Nonrandomised \nStudies in Meta -Analyses. 2014:  \n3. Sterne JAC, Savović J, Page MJ, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. Bmj. Aug \n28 2019;366:l4898. doi:10.1136/bmj.l4898  \n4. Moola S, Munn Z, Tufanaru C, et al. Chapter 7: Systematic reviews of etiology and risk. In : Aromataris E, Munn Z, \neds. JBI Reviewer's Manual . 2020. https://synthesismanual.jbi.global .  https://doi.org/10.46658/JBIMES -20-08  \n5. Guyatt GH, Oxman AD, Vist GE, et al. GRADE: an emerging consensus on rating quality of evidence and strength \nof recommendations. Bmj. Apr 26 2008;336(7650):924 -6. doi:10.1136/bmj.39489.470347.AD  \n6. Lewis E, Shinefield HR, Woodruff BA, et al. Safety of neonatal hepatitis B vaccine administration. Pediatr Infect \nDis J . Nov 2001;20(11):1049 -54. doi:10.1097/00006454 -200111000 -00009  \n7. Morgan HJ, Nold MF, Kattan GS, et al. Hepatitis B vaccination of preterm infants and risk of bronchopulmonary \ndysplasia: a cohort study, Australia. Vaccination contre l'hepatite B de prematures et risque de dysplasie \nbronchopulmonaire: etude de cohorte en  Australie, Vacunacion contra la hepatitis B en neonatos prematuros y riesgo \nde displasia broncopulmonar: estudio de cohortes en Australia. Bull World Health Organ . 2025;103(3):187 -193. \ndoi:10.2471/BLT.24.291683  \n8. Bassily S, Kotkat A, Gray G, et al. Comparative study of the immunogenicity and safety of two dosing schedules \nof hepatitis\n…[truncated]", "summary": "Disclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not  be construed to represent any agency determination or policy .  Page 1 of 84   ACIP BRIEFING MATERIALS FOR PUBLIC POSTING   The Safety of Hepatitis B Vaccines  administered within 24 hrs of birth and within 30 days of  birth: A Rapid Systematic Review   Table of Contents   Table of Tables  ................................…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-september-18-19-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-09-18-19/hep-b-at-birth-vax-safety-summary-508.pdf", "doc_date": "2025-09-18", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 84}
{"title": "effects hep b vax summary 508", "content": "Disclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not \nbe construed to represent any agency determination or policy .  Page 1 of 24 \n ACIP BRIEFING MATERIALS FOR PUBLIC POSTING  \n The Non -specific Effects of Hepatitis B Vaccines : A Rapid Systematic Revie w \nTable of Contents  \nA. Background  ................................ ................................ ................................ ................................ ................................ ..... 3 \nB. Methods  ................................ ................................ ................................ ................................ ................................ ..........  3 \nB.1. Key Question Development  ................................ ................................ ................................ ................................ ..... 3 \nB.2. Literature Search  ................................ ................................ ................................ ................................ ......................  3 \nB.3. Study Selection ................................ ................................ ................................ ................................ .........................  4 \nB.4. Data Extraction, Study Assessment, and Synthesis  ................................ ................................ ................................ . 6 \nB.5. GRADE -ing and Recommendation Development  ................................ ................................ ................................ .... 6 \nC. Summary of Evidence  ................................ ................................ ................................ ................................ .....................  7 \nC.1. Evidence Tables  ................................ ................................ ................................ ................................ ........................  7 \nC.1.a. GRADE -ed Summary of Findings  ................................ ................................ ................................ ...........................  7 \nD. Extracted Evidence from Included Studies  ................................ ................................ ................................ ...............  14 \nE. Search Strategies and Results  ................................ ................................ ................................ ................................ ..........  21 \nF. References  ................................ ................................ ................................ ................................ ................................ ........  23 \n \n  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not \nbe construed to represent any agency determination or policy .  Page 2 of 24 \n Table 1. PI/ECO(ST) Criteria for Key Question  ................................ ................................ ................................ .......................  3 \nTable 2. GRADE Table: Mortality and administration of monovalent hepatitis B vaccines in the first 6 years of life  .......  7 \nTable 3. GRADE Table: Mortality and administration of all hepatitis B -containing vaccines in the first 6 years of life ... 10 \nTable 4. GRADE Table: Cardiopulmonary outcomes and administration of hepatitis B vaccines in the first 6 years of life\n ................................ ................................ ................................ ................................ ................................ ..............................  14 \nTable 5. Characteristics of Studies Meeting Inclusion Criteria  ................................ ................................ ...........................  14 \nTable 6. Results of Studies Meeting Inclusion Criteria  ................................ ................................ ................................ ........  15 \nTable 7. Risk of Bias Assessment of Studies Meeting Inclusion Criteria  ................................ ................................ ............  19 \nTable 8. Primary Search of MEDLINE (OVID), Embase (OVID), CINAHL (Ebsco), Scopus, Cochrane Library  ......................  21 \n \nFigure 1. Results of the Study Selection Process  ................................ ................................ ................................ ...................  5 \n  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not \nbe construed to represent any agency determination or policy .  Page 3 of 24 \n A. Background  \nNon -specific effects of vaccination include broader impacts that may be conferred by vaccines beyond protection against \ntheir target pathogen, including the potential for effects on all -cause morbidity and mortality, non -targeted infections, \nallergic and a topic disease, autoimmune and immune -mediated disease, and malignancy.1 While the non -specific effects \nof certain vaccines, including Bacille Calmette -Guérin (BCG) vaccine, measles -containing vaccines, and diphtheria -\ntetanus -pertussis vaccines, among others,1 have been previously studied, an evidence -based review of non-specific \neffects associated with hepatitis B -containing vaccines is needed. Given the need to ensure the safety of all vaccination s \nadministered in childhood, we propose a systematic review of the literature to understand any non -specific effects of \nchildhood vaccinations. In this report, we focused on the literature that evaluated non -specific effects of hepatitis B \nvaccination .    \nB. Methods  \nB.1. Key Question Development  \nThe Key Question  was developed  by infectious disease and systematic review methodology subject matter experts  \nusing the PICO  framework2 (Population, Intervention, Comparator, and Outcome ). The Key Question  and PI /ECO(ST) \nCriteria  used to guide the literature review are:  \n1. What are the non -specific effects of childhood vaccines?  \nTable 1. PI/ECO(ST) Criteria for Key Question  \nPI/ECO(ST) ELEMENT  Description for this Review  \nPopulation  Infants and children through 6 years of  age \nIntervention or \nExposure  Hepatitis A (HAV) – Havrix, VAQTA, Hepatitis B (HBV) – Recombivax HB, Engerix -B, Rotavirus \n– ROTARIX, RotaTeq, Diphtheria, tetanus, acellular pertussis (DTaP) – Infanrix, Daptacel, \nHaemophilus influenzae type B (Hib) – PedvaxHIB, ActHIB, Hiberix, Poliomyel itis/polio (IPV) – \nIPOL, Pneumococcal (PCV15, PCV20) –VAXNEUVANCE, Prevnar 20, Measles, mumps rubella \n(MMR) – PRIORIX, M -M-R II, Varicella - Varivax  \nRSV – Nirsevimab, Clesrovimab, Combination vaccines – Pediarix, Kinrix, Quadracel, Vaxelis, \nPentacel, ProQuad  \nComparator (if \napplicable)  Any or none  \nOutcome(s)  Non -specific effects, all -cause morbidity, all -cause mortality (death), non -targeted infection \n(sepsis, respiratory tract), allergic and atopic disease (asthma, eczema, atopic dermatitis, \nfood allergy), autoimmune and immune -mediated disease (type 1 diabet es mellitus, \ninflammatory bowel disease – ulcerative colitis and Crohn’s disease, juvenile idiopathic \narthritis, systemic lupus erythematosus, Hashimoto’s thyroiditis, alopecia), malignancy \n(cancer, leukemia)   \nSetting  Any \nTime Frame  Any publication years  \nAny duration of follow up  \n \nB.2. Literature Search  \nA CDC informationist (J T) developed search strategies from the Key Question s and PICO criteria,  and performed the \nsearch in MEDLINE, EMBASE , CINAHL , and Cochrane Library  from  the start of each database to August  20, 2025 . \nSearch strategies and results are provided in  Table 8.  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not \nbe construed to represent any agency determination or policy .  Page 4 of 24 \n B.3. Study Selection  \nResults of the literature searches were uploaded into EndNote 21 (Clarivate Analytics©, Thomson Reuters, New \nYork, NY, USA), duplicate records were removed, and unique t itles and abstracts  were uploaded to Covidence \n(Veritas Health Innovation Ltd., Melbourne, VIC, Australia) where a second round of deduplication was conducted.  \nAs this was the first of several planned systematic  reviews on non -specific effects of childhood vaccination, a \nkeyword search was conducted to filter records with title and abstracts  relevant for hepatitis B vaccines (Hepatitis B, \nHBV, HepB, Engerix -B, Recombivax HB, Pediarix, Vaxelis). Two reviewers (EQ, EM, BE ) independently screened all \ntitles and abstracts and removed irrelevant references. Relevant  full texts  were screened independent ly by two  \nreviewers  (EQ, LZ ) and disagreements were resolved by consensus . All studies were screened according to the pre -\nidentified exclusion criteria below, and results of the study selection process are provided in Figure 1 . \n \nCriteria for excluding studies from the literature review include:  \n1. No full text  available;   \n2. Not available in English;  \n3. Not relevant to key question ; \n4. No population of interest  (study popula tion did not include children vaccinated at ≤6 years of age ; \n5. No intervention of interest  (no hepatitis B vaccine exposure) ; \n6. No outcome of interest;  \n7. No primary data  or secondary data not systematically collected  (no reproducible methods) ; or \n8. Insufficient me thodologic reporting (i.e., m eeting abstract  or poster );  \n \n \n \n \n \n \n \n \n \n \n \n \n \n  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not \nbe construed to represent any agency determination or policy .  Page 5 of 24 \n  \nFigure 1. Results of the Study Selection Process   \n \n \n \n \n\n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 6 of 24 \n B.4. Data Extraction , Study Assessment , and Synthesis  \nData from studies meeting inclusion criteria were independently extracted by two reviewers using a standardized Microsoft Excel (2021) form, and \ndifferences were reconciled by discussion. Extracted data included study characteristics  (Table 5). Outcome data were extracted as presented in the studies \nor calculated using data provided. For the purposes of this review, statistical significance was defined as p ≤ 0.05 . The risk of bias for each study was assessed \naccording to study type  using standardized  risk of bias tools  appropriate to the identified st udy type. Tools were modified to specify region, time, age , \nweight, and  prematurity, as  confounding factors  and to include an assessment of conflict -of-interest  disclosures . The Newcastle -Ottawa Scale was used for \ncohort and case control studies , R.O.B2. for randomized controlled trials (RCTs) , and JBI tools were used to assess the risk of bias for Case Series and \nSystematic Reviews . The signaling questions used to assess study conduct and risk of bias and results are presented in Table 6. The evidence was narratively \nsynthesized for  each  outcome domain, and for specific outcomes where definitions aligned.  \nB.5. GRADE -ing and Recommendation Development  \nThe Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach  was used to assess the  risk of bias , imprecision, \ninconsistency, and indirectness , and final confidence for the body of evidence  foreach outcome .3 \n  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 7 of 24 \n C. Summary of Evidence  \nC.1. Evidence  Tables  \nC.1.a. GRADE -ed Summary of Findings  \nKey Question: Among children, what are the non-specific effects of hepatitis B vaccine s administered in the f irst 6 years of life ?  \nTable 2. GRADE Table: Mortality and administration of monovalent hepatitis B vaccines in the first 6 years of life  \nOutcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence  \nAll Mortality \nOutcomes, \nMonovalent \nHepatitis B \nVaccines  Evidence  from 3 cohorts  suggests hepatitis B vaccine \nadministration may  not be associated with an increase  \nin risk of mortality in high -income countries ( HIC) and \nmay be associated with an increase in risk in low-and \nmiddle -income countries ( LMIC ). Two  studies from HIC \nsuggest  either a protective or no effect of hepatitis B \nvaccination on mortality and one study from an LMIC \nsuggest s an increase in mortality  after hepatitis B \nvaccination . Evidence  from 1 cohort and 1 nested case \nseries is inconsistent about  sex-specific mortality after \nreceipt of hepatitis  B vaccines; one study suggest s both \nno difference and an increase in the female -to-male \nmortality ratio and one study sugges ts no difference in \nmortality by sex. One cohort suggest s either  a protective \nor no effect on hepatitis B vaccines and cancer -related \nand cardiovascular -related mortality.  4 Studies  \n(N=46,628)  Some concernsa No concerns  No concernsb Some \nconcernsc Very low  \nconfidence  \nMortality  Summary: The evidence from 2 cohort studies (He 2022 \nand Morgan 2025) in HIC suggests no association or a \ndecrease in mortality after hepatitis B vaccination. The \nevidence from 1 cohort in Guinea -Bissau (Garly 2004) \nsuggests an increase in mortality after hepatitis B \nvaccination; these findings had some concerns  for bias.   3 Cohorts  \n(He 2022, \nMorgan \n2025, Garly \n2004)  \n(N=46,515)  Some concernsd No concerns  No concernse Some  \nconcernsf Very low  \nconfidence  \n \na Confounding by weight/ weight -for-age z score  or health service utilization  in 2 studies, temporal  variation in 2 studies, regional differences in 2 studies,  concern for  exposure \nmisclassification in 1 study  and inadequate follow up in 1 stud y.  \nb Inconsistency may be explained by direct and indirect population differences . \nc Aaby 2006 and Garly 2004 are conducted in LMIC population s. \nd Confounding by weight/weight -for-age z score  or health service utilization  in 2 studies, temporal variation in 2 studies, regional differences in 2 studies, and inadequate follow \nup in 1 stud y. \ne Inconsistency may be explained by direct and indirect population differences . \nf Garly 2004 is conducted in a LMIC population . \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 8 of 24 \n Outcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence  \n• One cohort (He, 2022) of 36,791 participants in \nthe National Health and Nutrition Examination \nSurvey in the United States suggested a \nreduced risk of all -cause mortality associated \nwith hepatitis B vaccination [aHR 0.78 (95%CI: \n0.68 -0.90); 390/10,785 PY vs  4,185/26,006 PY]  \nfollowing vaccination  prior to 1.5 years of age  \nwith a median follow -up of 8 years .  \n• One cohort (Morgan 2025) of extremely \npreterm infants (<29 weeks gestation) in \nAustralia’s Surveillance of Adverse Events \nFollowing Immunization in the Community \nsuggested there is no difference in risk of death \nduring the first 3 months of life when \ncompa ring infants with a record of receiving \nhepatitis b vaccine within 24 hours of birth to \ninfants with no record of receiving hepatitis B \nvaccine within 24 hours of life  [aRR: 1.13; \n(95%CI: 0.42 -2.81); 7/306 vs 14/512].  \n• One cohort study (Garly 2004) of 8,906 children \nfrom Bandim Health Project's Health and \nDemographic Surveillance System in Guinea -\nBissau suggested increased mortality rate at 7 ½ \n- 12 months of age compared to mortality rate \nat 1 ½ - 7 ½ months of age [aMR R: 1.62, 95% CI: \n1.09, 2.41) for the birth cohort in which most \nchildren received hepatitis B vaccination \n(Hepaccine) at 7 ½ months of age. In a \nsubgroup analysis  within a measles vaccine \n(MV) trial , mortality rate for children 7 ½ -12 \nmonths of age was ele vated among those \nreceiving hepatitis B vaccine (+MV) compared \nto hepatitis B -unvaccinated (+MV) children \n(5,441 children), [MRR 1.81 (95%CI: 1.19 -2.75)].  \nHepaccine is not approved for use in the United \nStates.  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 9 of 24 \n Outcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence  \nFemale and male \nmortality  One cohort (Garly 2004) from Bandim Health Project's \nHealth and Demographic Surveillance System in Guinea -\nBissau  suggested elevated female -to-male (F/M) \nmortality in a subgroup of 5,061 children ages, evaluated \nthrough 12 and 24 months within a 2 -dose mea sles trial, \namong those vaccinated for hepatitis B ( Hepaccine) 12 \nmonths: [F/M MRR 1.66 (95%CI: 0.80 -3.45); 18/143.8 PY \nvs 12/159.1 PY] 24 months: [F/M MRR 2.20 (95%CI: 1.07 -\n4.54); 22/358 PY vs 11/394.3 PY].  \n \nIn a nested case series (Aaby 2006) in The Gambia’s \nMedical Research Council  Laboratories’ Demographic \nSurveillance System, hepatitis B vaccine was the last \nvaccination received among 7% (4/60) of female infants \nand 0% (0/53) male infants who died  and had vaccination \nstatus available from 2 -17 months of age .   1 Cohort  \n(Garly 2004) \n(N= 8,906)  \n \n1 Case \nseries  \n(Aaby 2006) \n(N=113)  Some concernsg No concerns  No concerns  Some \nconcernsh Very l ow \nconfidence  \nCancer -related \nmortality  One cohort (He 2022) of 36,791 participants in the United \nStates’ National Health and Nutrition Examination Survey \nsuggested a trend toward reduction in cancer -related \nmortality among people 6 years and older who had \nreceived a hepatitis B vaccine compared to those who \nwere unvaccinated for hepatitis B [aHR 0.76 (95%CI: 0.58 -\n1.00 ); 97/10,785 PY vs 881/26,006 PY ]. Most of the \nvaccinated population had received hepatitis B vaccine in \nthe first 1.5 years of life  with a median follow -up of 8 \nyears . \n 1 Cohort  \n \n(He 2022) \n(N=36,791)  No concerns  No concerns  No concerns  No concerns  Low confidence  \nCardiovascular -\nrelated mortality  One cohort (He 2022) of 36,791 participants in the United \nStates’ National Health and Nutrition Examination Survey \nsuggested no association between cancer -related \nmortality in people 6 years and older and hepatitis B \nvaccination [aHR 0.83 (95%CI: 0.60 -1.15 ); 53/10,785 PY vs \n732/26,006 PY ]. Most of the vaccinated population had \nreceived hepatitis B vaccine in the first 1.5 years of life  \nwith a median follow -up of 8 years . \n 1 Cohort  \n \n(He 2022) \n(N=36,791)  \n No concerns  No concerns  No concerns  No concerns  Low confidence  \n \ng Confounding by weight/weight -for-age z score or health service utilization and concern for exposure misclassification  in 1 study . \nh Conducted in LMIC population . \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 10 of 24 \n  \nTable 3. GRADE Table: Mor tality  and administration of all hepatitis B -containing vaccines in the first 6 years of life  \nOutcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence  \nAll mortality \noutcomes, all \nhepatitis B -\ncontaining vaccines  Evidence  from 4 cohorts is inconclusive about whether \nreceipt of a hepatitis B -containing vaccine is associated \nwith mortality . Studies  (n=2)  from HIC  suggest  a \nprotective or no effect of hepatitis B vaccination on \nmortality and studies (n=2) from LMIC  suggest  an \nincrease in mortality  after hepatitis B vaccination.  \nEvidence  from 4 cohorts and 1 nested case series about \nsex-specific mortality after hepatitis B -containing \nvaccines varies . One cohort suggested either a \nprotective or no effect of hepatitis -B co ntaining vaccines \non cancer -related and cardiovascular -related mortality.   \nFindings may differ due to differences in types of \nvaccines administered. Some studies evaluated \nmonovalent hepatitis -B vaccines , and some studies \nevaluated pentavalent vaccines, which contain  antigens \nto protect against diphtheria, tetanus, pertussis, \nhaemophilus  influenzae type B and hepatitis B.  8 Studies  \n(N=82,849)  Some \nconcernsi No concerns  No concernsj Some concernsk Very low  \nconfidence  \nMortality  Summary: The evidence from 2 cohort studies (He 2022 \nand Morgan 2025) in HIC suggests no increase in the risk \nof mortality with hepatitis -B vaccination at a follow up of \n3 months of life and a median follow up of 8 years of life .  \n• One cohort (He, 2022) of 36,791 participants in \nthe United States’ National Health and \nNutrition Examination Survey suggested a \nreduced risk of all -cause mortality associated \nwith hepatitis B vaccination [aHR 0.78 (95%CI: 4 Cohorts  \n(He 2022, \nMorgan \n2025, Fisker \n2018, Garly \n2004)  \n(N=53,609)  Some concernsl No concerns  No concernsm Some concernsn Very low \nconfidence  \n \ni Confounding by weight/weight -for-age z score  or health service utilization  in 4 studies, temporal variation in 3 studies, regional differences in 2 studies, concern for exposure \nmisclassification in 1 study , outcome misclassification in 2 studies  and inadequate follow up in 1 stud y. \nj Inconsistency may be explained by direct and indirect population differences  \nk Aamand 2023, Hanifi 2021, Fisker 2018, Fisker 2016, Aaby 2006, Garly 2004 are conducted in a LMIC population  \nl Confounding by weight/weight -for-age z score or health service utilization in 3 studies,  age at administration in 1 study,  temporal variation in 2 studies, regional differences in 2 \nstudies, concern for outcome misclassification in 1 study and inadequate follow up in 1 stud y. \nm Inconsistency may be explained by direct and indirect population differences  \nn Fisker 2018 and Garly 2004 are conducted in a LMIC population  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 11 of 24 \n Outcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence  \n0.68 -0.90); 390/10,785 PY vs 4,185/26,006 PY]  \nfollowing vaccination prior to 1.5 years of age \nwith a median follow -up of 8 years .   \n• One cohort (Morgan 2025) of extremely \npreterm infants (<29 weeks gestation) in \nAustralia’s Surveillance of Adverse Events \nFollowing Immunization in the Community \nsuggested there is no difference in risk of death \nduring the first 3 months of life when \ncompa ring infants with a record of receiving \nhepatitis b vaccine within 24 hours of birth to \ninfants with no record of receiving hepatitis B \nvaccine within 24 hours of life  [aRR: 1.13; \n(95%CI: 0.42 -2.81); 7/306 vs 14/512].  \nIndirect  evidence from 2 cohort studies in Guinea -Bissau \n(Fisker 2018, Garly 2004) suggests there may be  an \nincrease in  the risk of  mortality after  hepatitis -B \ncontaining vaccination  (pentavalent and hepatitis B \nvaccine ). There  are concerns about the generalizability of \nLMIC infant mortality data to HIC infants.  \n• In on e cohort (Fisker 2018) in Guinea -Bissau, \npentavalent vaccine is administered at a \nyounger  age than measles vaccine.  7,094 \ninfants in Bandim Health Project's Health and \nDemographic Surveillance System suggested no \nassociation between receiving  a measles \nvaccine first and then a pentavalent vaccine  \n[aHR 1.19 (95%CI: 0.84 -1.69); 43/2,847 PY vs \n160/14,186 PY], receiving missing pentavalent \ndoses [aHR 1.87 (95%CI: 0.96 -3.65); 10/430 PY \nvs 160/14,186 PY] or not receiving missing \npentavalent doses [aHR 0.93  (95%CI: 0.57 -\n1.54); 17/1,537 PY vs 160/14,186 PY] compared \nto receipt of a  pentavalent vaccine first and \nthen a  measles vaccine.  \n• One cohort study (Garly 2004) of 8,906 children \nfrom Bandim Health Project's Health and \nDemographic Surveillance System in Guinea -\nBissau suggested increased mortality rate at 7 \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 12 of 24 \n Outcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence  \n½ - 12 months of age compared to mortality \nrate at 1 ½ - 7 ½ months of age [aMRR: 1.62, \n95% CI: 1.09, 2.41) for the birth cohort in which \nmost children received hepatitis B vaccination \n(Hepaccine) at 7 ½ months of age. In a \nsubgroup analysis  within a measles vaccine \n(MV) trial , mortality rate for children 7 ½ -12 \nmonths of age was elevated among those \nreceiving hepatitis B vaccine (+MV) compared \nto hepatitis B -unvaccinated (+MV) children \n(5,441 children), [MRR 1.81 (95%CI: 1.19 -2.75)]. \nHepaccine is not appro ved for use in the United \nStates.  \nFemale -to-male \nmortality  Summary: Indirect  evidence from 4 cohort studies in \nLMIC  suggests there may be an increase in risk of \nmortality among female compared to male  children \nreceiving hepatitis B vaccines. An increased female -to \nmale mortality rate was observed in 2 cohorts (Hanifi \n2021, Fisker 2016) but not in 1 cohort (Aamand 2023). \nOne cohort in LMIC reported no difference in female to \nmale mortality at 12 months of age and an increase in \nfemale mortality at 24 months  (Garly 2004).  \n• One cohort (Aamand 2023) of 12,753 infants in \nBandim Health Project's Health and \nDemographic Surveillance System in Guinea -\nBissau suggested no association between \nfemale and male mortality and pentavalent \nvaccination [F/M aMRR 1.01 (95%CI: 0.82 -1.25); \n73/2,901 PY vs 78/2,930 PY )] through 6 months \nof follow -up post -vaccination . \n• One cohort (Hanifi 2021) of 7,644 children ages \n6 weeks - 9 months in the International Center \nfor Diarrheal Diseases Research Bangladesh’s 4 Cohorts  \n(Aamand \n2023, Hanifi \n2021, Fisker \n2016, Garly \n2004)  \n(N=38,033)  \n \n1 Case series  \n(Aaby 2006) \n(N=113)  \n Some \nconcernso Some  concernsp No concerns  Some concernsq Very low \nconfidence  \n \no Confounding by weight/weight -for-age z score or health service utilization  in 2 studies  and concern for exposure misclassification  in 1 study and outcome misclassification in 1 \nstudy . \np Wide confidence intervals in the study reporting the highest female to male mortality differences . \nq Conducted in LMIC population s. \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 13 of 24 \n Outcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence  \nHealth and Demographic Surveillance System \nsuggested elevated female -to-male mortality \nafter pentavalent vaccination [F/M MRR 9.91 \n(95%CI: 1.16 -84.44)].  \n• One cohort (Fisker 2016) of 8,730 infants in \nBandim Health Project's Health and \nDemographic Surveillance System in Guinea -\nBissau suggested elevated female -to-male \nmortality after pentavalent vaccination [F/M \naMRR 1.86 (95%CI: 1.16 -2.98), 52/1,939 PY vs \n31/1,999 PY]  through 6 -months post -\nvaccination . \n• One cohort (Garly 2004) from Bandim Health \nProject's Health and Demographic Surveillance \nSystem in Guinea -Bissau suggested no \ndifference in  F/M mortality at 12 months [F/M \nMRR 1.66 (95%CI: 0.80 -3.45); 18/143.8 PY vs \n12/159.1 PY] and elevated F/M mortality at 24 \nmonths  [F/M MRR 2.20 (95%CI: 1.07 -4.54); \n22/358 PY vs 11/394.3 PY]. after hepatitis B \nvaccination ( Hepaccine)  in a subgroup of 5,061 \nchildren In a nested case series (Aaby 2006) in \nThe Gambia’s Medical Research Council  \nLaboratories’ Demographic Surv eillance \nSystem, hepatitis B vaccine was the last \nvaccination received by  7% (4/60) of female \ninfants and 0% (0/53) male infants who died  \nand had vaccination status information \navailable .  \nCancer -related \nmortality  One cohort (He 2022) of 36,791 participants in the United \nStates’ National Health and Nutrition Examination Survey \nsuggested a trend toward a reduction in  cancer -related \nmortality among people 6 years and older who had \nreceived a hepatitis B vaccin e compared to those who \nwere unvaccinated for hepatitis B  [aHR 0. 76 (95%CI: 0. 58-\n1.00 ]. Most of the vaccinated population had received \nhepatitis B vaccine in the first 1.5 years of life  with a \nmedian follow -up of 8 years.  \n 1 Cohort  \n \n(He 2022 ) \n(N=36,791)  \n No concerns  No concerns  No concern  No concerns  Low \nconfidence  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 14 of 24 \n Outcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence  \nCardiovascular -\nrelated mortality   One cohort (He 2022) of 36,791 participants in the \nUnited States’ National Health and Nutrition Examination \nSurvey suggested  no association between cancer -related \nmortality in people 6 years and older and hepatitis B \nvaccination [aHR 0.83 (95%CI: 0.60 -1.15] . Most of the \nvaccinated population had received hepatitis B vaccine in \nthe first 1.5 years of life  with a median follow -up of 8 \nyears . \n 1 Cohort  \n \n(He 2022 ) \n(N=36,791)  \n No concerns  No concerns  No concerns  No concern s Low \nconfidence  \n \nTable 4. GRADE Table: Cardiopulmonary outcomes and administration of hepatitis B vaccines in the first 6 years of life  \nOutcome  Summary  Studies  Risk of Bias  Imprecision  Inconsistency  Indirectness  Confidence  \nCardiopulmonary  The evidence from 1 cohort suggests that receipt of hepatitis \nB vaccine in the first 24 hours of life is not associated with an \nincrease in the risk of bronchopulmonary dysplasia.   1 Stud y \n(N=818) Som e \nconcerns  No concerns  \n No concerns  \n No concerns  \n Low \nconfidence  \n \nBronchopulmonary \ndysplasia  One cohort (Morgan 2025) of extremely preterm infants (<29 \nweeks gestation) in Australia’s Surveillance of Adverse Events \nFollowing Immunization in the Community suggested there is a \nreduction in risk of bronchopulmonary dysplasia when \ncomparing preterm infants  with a record of receiving hepatitis \nb vaccine within 24 hours of birth to preterm  infants with no \nrecord of hepatitis B vaccine within 24 hours of birth [aRR: \n0.83; (95%CI: 0.68 -1.0); 155/306 vs 317/512].  \n 1 Cohort  \n \n(Morgan \n2025 N = \n818)  No concerns  No concerns  No concerns  No concerns  Low \nconfidence  \n \nD. Extracted Evidence from Included Studies  \nTable 5. Characteristics of Studies Meeting Inclusion Criteria  \nAuthor \nYear  Study \ndesign  Data Collection \nPeriod  Vaccine  Sample size, N  Surveillance System (if Applicable)  Country  \nAaby 20064 Nested case \nseries  1998 -2002  Hepatitis B [unspecified \nmanufacturer]  113 children who had died  and \nhad vaccination status  Medical Research Council  Laboratories' \nDemographic Surveillance  System in Farafenni  The Gambia  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 15 of 24 \n Author \nYear  Study \ndesign  Data Collection \nPeriod  Vaccine  Sample size, N  Surveillance System (if Applicable)  Country  \nAamand \n20235 Cohort  September 1, 2008 – \nDecember 31, 2017  Pentavalent *  12,753 children  Bandim Health Project's Health and \nDemographic Surveillance System  Guinea -Bissau  \nFisker \n20166 Cohort  September 1, 2008  – \nApril 18, 2011  Pentavalent * 8,730 children  Bandim Health Project's Health and \nDemographic Surveillance System  Guinea -Bissau   \nFisker \n20187 Cohort  September 1, 2008 – \nJune 22, 2015  Pentavalent *  7,094 children  \n Bandim Health Project's Health and \nDemographic Surveillance System  Guinea -Bissau   \nGarly 20048 Cohort  March 1994 – February \n2000  Hepatitis B (Hepaccine)  8,906 children  Bandim Health Project's Health and \nDemographic Surveillance System   Guinea -Bissau   \nHanifi \n20219 Cohort  June 29, 2011 – April \n20, 2016  Pentavalent * 7,644 children  International Center for Diarrheal Diseases \nResearch Bangladesh's Health and Demographic \nSurveillance System in Chakaria  Bangladesh  \nHe 202210 Cohort  1999 – 2018  Hepatitis B  [Unspecified \nmanufacturer, \nthimerosal -free]  36,791 participants  National Health and Nutrition Examination \nSurvey  United States  \nMorgan \n202511 Cohort  January  1, 2017 – \nDecember  31, 2020  Hepatitis B  [Engerix -B \nor HB -Vax-II, \nthimerosal -free]  818 extremely preterm infants  Surveillance of Adverse Events Following \nImmunization in the Community  Australia  \n*Pentavalent vaccine : Diphtheria -Tetanus -whole cell Pertussis -Hemophilus influenzae type B -Hepatitis B  \nTable 6. Results of Studies Meeting Inclusion Criteria  \nStudy  Study \nType  Exposure  Outcome  Follow -up Outcome \nIdentification  Intervention \n% or rate  \n(n/N  or \nperson -time ) Control %  or \nrate  (n/N or \nperson -time)  p-\nvalue  Measure of \nAssociation  \n(95% CI)  Adjusted  Risk of \nBias  \nAaby 2006  Nested \ncase \nseries  Hepatitis B as \nlast vaccin e Female d eath s Vaccination \nthrough 18 \nmonths of age  Verbal autopsy  7% (4/60)  NA NA NA No High risk \nof bias  \nAaby 2006  Nested \ncase \nseries  Hepatitis B as \nlast vaccine  Male deaths  Vaccination \nthrough 18 \nmonths of age  Verbal autopsy  0% (0/53) NA NA NA No High risk \nof bias  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 16 of 24 \n Study  Study \nType  Exposure  Outcome  Follow -up Outcome \nIdentification  Intervention \n% or rate  \n(n/N  or \nperson -time ) Control %  or \nrate  (n/N or \nperson -time)  p-\nvalue  Measure of \nAssociation  \n(95% CI)  Adjusted  Risk of \nBias  \nAamand \n2023  Cohort  Pentavalent  \nvaccination  Female/male \nmortality  Vaccination \nthrough 6 \nmonths post -\nvaccination  Reported \ncause of death  25.5 per 1,000 \nperson -years  \n(73/2,901 PY)  26.6 per 1,000 \nperson -years  \n(78/2,930 PY)  NR 1.01 (0.82 -\n1.25)  Yes Low risk of \nbias \nFisker 2016  Cohort  Pentavalent \nvaccination  Female/male \nmortality  Vaccination \nthrough either \nSubsequent \nvaccination \ncontact or 6 \nmonths post -\nvaccination  Verbal \nautopsy, \nmedical review  26.8 per 1,000 \nPY (52/1,939 \nPY) 15.5 per 1,000 \nPY (31/1,999 \nPY) 0.01  1.86 (1.16-\n2.98) Yes Moderate \nrisk of bias  \nFisker 2018  Cohort  Pentavalent \nafter measles \nvaccine  Mortality  First home visit \nafter 9 months \nto 5 years of \nage Interview  15.1 per 1,000 \nPY (43/2,847 \nPY) 11.3 per 1,000 \nPY (160/14,186  \nPY) NR 1.19 (0.84 -\n1.69)  Yes High risk \nof bias  \nFisker 2018  Cohort  Received \nmissing \nPentavalent \nvaccine  at \nmost recent \nvisit Mortality  First home visit \nafter 9 months \nto 5 years of \nage Interview  23.3 per 1,000 \nPY (10/430 PY)  11.3 per 1,000 \nPY (160/14,186 \nPY) NR 1.87 (0.96 -\n3.65)  Yes High risk \nof bias  \nFisker 2018  Cohort  Did not \nreceive \nmissing \npentavalent \nvaccine  at \nmost recent \nvisit Mortality  First home visit \nafter 9 months \nto 5 years of \nage Interview  11.1 per 1,000 \nPY (17/1 ,537 \nPY) 11.3 per 1,000 \nPY (160/14,186  \nPY) NR 0.93 (0.57 -\n1.54)  Yes High risk \nof bias  \nGarly 2004  Cohort  7 ½ - 12 vs 1 ½ \n- 7 ½ months \nof age, cohort \nreceiving \nhepatitis B \nvaccine  \n(Hep accine)  Mortality  1.5 months \nthrough 12 \nmonths of age  Death \nregistration \nsystem  \n NR NR 0.03  \n 1.62 (1.09 -\n2.41)  \n Yes Moderate \nrisk of bias  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 17 of 24 \n Study  Study \nType  Exposure  Outcome  Follow -up Outcome \nIdentification  Intervention \n% or rate  \n(n/N  or \nperson -time ) Control %  or \nrate  (n/N or \nperson -time)  p-\nvalue  Measure of \nAssociation  \n(95% CI)  Adjusted  Risk of \nBias  \nGarly 2004  Cohort  Hepatitis B \nvaccination  \n(Hepaccine)  Mortality  1.5 months \nthrough 12 \nmonths of age  Death \nregistration \nsystem  \n nr/876  nr/4565  NR 1.81 (1.19 -\n2.75)  No Moderate \nrisk of bias  \n \nGarly 2004  Cohort  Hepatitis B \n(Hepaccine) + \nmeasles \nvaccine vs \nmeasles \nvaccine  Female/male \nmortality  7 ½ months \nthrough 12 \nmonths of age  Death \nregistration \nsystem  12.5% \n(18/143.8 PY)  7.5% (12/159.1 \nPY) NR 1.66 (0.80 -\n3.45)  No Moderate \nrisk of bias  \nGarly 2004  Cohort  Hepatitis B  \n(Hepaccine)  + \nmeasles \nvaccine vs \nmeasles \nvaccine  Female/male \nmortality  9 months \nthrough 24 \nmonths of age  Death \nregistration \nsystem  \n 6.1% (22/358 \nPY) 2.8% (11/394.3  \nPY) 0.04  2.20 (1.07 -\n4.54)  No Moderate \nrisk of bias  \nHanifi 2021  Cohort  Pentavalent \nvaccination  Female/male \nmortality  6 weeks \nthrough 9 \nmonths of age  Household \nvisit 14.3 per 1,000 \nPY (9/618 PY)  1.4 (1/667 PY)  0.01  9.91 (1.16 -\n84.44)  Yes High risk \nof bias  \nHe 2022  Cohort  Hepatitis B \nvaccination \n[Unspecified \nmanufacturer, \nthimerosal \nfree All-cause mortality  Median follow -\nup of 8 years  NHANES \nLinked \nMortality File , \n1999 -2018  2.8% \n(390/10,785)  11.8% \n(4,185/26,006)  NR 0.78 (0.68 -\n0.90)  Yes Low risk of \nbias \nHe 2022  Cohort  Hepatitis B \nvaccination \n[Unspecified \nmanufacturer, \nthimerosal \nfree Cancer -related \nmortality  Median follow -\nup of 8 years  \n NHANES \nLinked \nMortality File  \n1999 -2018  \n 0.7% \n(97/10,785)  2.6% \n(881/26,006)  \n NR 0.76 (0.58 -\n1.00)  Yes Low risk of \nbias \n \nHe 2022  Cohort  Hepatitis B \nvaccination \n[Unspecified \nmanufacturer, Cardiovascular -\nrelated mortality  Median follow -\nup of 8 years  \n NHANES \nLinked \nMortality File , \n1999 -2018  \n 0.4% \n(53/10,785)  1.9% \n(732/26,006)  NR 0.83 (0.60 -\n1.15)  Yes Low risk of \nbias \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 18 of 24 \n Study  Study \nType  Exposure  Outcome  Follow -up Outcome \nIdentification  Intervention \n% or rate  \n(n/N  or \nperson -time ) Control %  or \nrate  (n/N or \nperson -time)  p-\nvalue  Measure of \nAssociation  \n(95% CI)  Adjusted  Risk of \nBias  \nthimerosal  \nfree]  \nMorgan \n2025  Cohort  Hepatitis B \nvaccine within \n24 hours of \nbirth  (Engerix -\nB and H -B-Vax \nII, thimerosal -\nfree)  All-cause mortality  Birth to 3 \nmonths  Victorian  \nDeaths Index \ndata set  2.3%  \n(7/306 ) 2.7%  \n(14/512 ) 0.87 1.13 (0.42 -\n2.81)  Yes Some \nconcerns  \nMorgan \n2025  Cohort  Hepatitis B \nvaccine within \n24 hours of \nbirth  \n(Engerix -B and \nH-B-Vax II, \nthimerosal -\nfree)  Bronchopulmonary \ndysplasia  Birth to 3 \nmonths  ICD-10 50.7%  \n(155/306 ) 61.9%  \n (317/512 ) NR 0.83 (0.68 -\n1.00) Yes Some \nconcerns  \n \n \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 19 of 24 \n Table 7. Risk of Bias Assessment of Cohort Studies Meeting Inclusion Criteria  \nSTUDY NAME  Aamand 2023  Fisker 2016  Fisker 2018  Hanifi 2021  He 2022  Garly 2004  Morgan 2025  \nSIGNALING QUESTION  Cohort  Cohort  Cohort  Cohort  Cohort  Cohort  Cohort  \nSelection         \nWere the groups similar and recruited from the same population?  Yes  Yes  Yes  Yes  Yes  Yes  Yes  \nWere exposures/ interventions measured similarly to assign patients/ \npeople?  Yes  Yes  Yes  Yes  Yes  Yes  Yes  \nWas the intervention/ exposure measured in a valid & reliable way?  Yes  Yes  Yes  Unclear  Yes  Yes  Yes  \nComparability/ Confounding         \nComparability of groups on basis of design or analysis  study controls/ adjusts for region  study controls/ adjusts for region  study controls/ adjusts for region  study controls/ adjusts for region  study controls/ adjusts for region  study does not control/ adjust for region  study does not control/ adjust for region  \nComparability of groups on basis of design or analysis  study controls/ adjusts for time period  study does not control/ adjust for time period  study controls/ adjusts for time period  study controls/ adjusts for time period  study does not control/ adjust for time period  study controls/ adjusts for time period  study does not control/ adjust for time period  \nComparability of groups on basis of design or analysis  study controls/ adjusts for weight  study controls/ adjusts for weight  study does not control/ adjust for weight  study does not control/ adjust for weight  study does not control/ adjust for weight  study does not control/ adjust for weight  study controls/ adjusts for weight  \nComparability of groups on basis of design or analysis  study does not control/ adjust for prematurity  study does not control/ adjust for prematurity  study does not control/ adjust for prematurity  study does not control/ adjust for prematurity  study does not control/ adjust for prematurity  study does not control/ adjust for prematurity  study controls/ adjusts for prematurity  \nComparability of groups on basis of design or analysis  study controls/ adjusts for age at administration  study controls/ adjusts for age at administration  study does not control/ adjust for age at administration  study controls/ adjusts for age at administration  study controls/ adjusts for age at administration  study controls/ adjusts for age at administration  study controls/ adjusts for age at administration  \nNo residual confounding concerns exist  Yes  No No Unclear  Yes  No No \nOutcome         \nWere the subjects free of the outcome of interest at the start of the \nstudy?  Yes  Yes  Yes  Yes  Yes  Yes  Yes  \nWere the outcomes measured in a valid and reliable way?  Unclear  Yes  No No Yes  Yes  Yes  \nWas the same method of ascertainment or assessment of outcome \ndone for both groups?  Yes  Yes  Yes  Yes  Yes  Yes  Yes  \nWas the non -response rate similar across both groups?  Not applicable  Not applicable  Not applicable  Not applicable  Not applicable  Unclear  Not applicable  \nFollow up         \nWas the follow up time reported and long enough for outcomes to \noccur?  Yes  Yes  Yes  Yes  Yes  Yes  Unclear  \nWas follow up complete, and if not, were the reasons for loss to follow \nup described and explored?  Yes  Yes  Yes  Unclear  Yes  Unclear  Yes  \nWere strategies to address incomplete follow up utilized?  Yes  Yes  Yes  Yes  Not applicable  Yes  Not applicable  \nAnalysis         \nWere appropriate statistical analyses used?  Yes  Yes  Yes  Yes  Yes  Yes  Yes  \nCOI         \nWere conflicts of interest disclosed and no obvious conflicts exist?  Yes  Yes  Yes  Yes  Yes  No Yes  \nRisk -of-bias judgement  Low risk of bias  Some concerns  High risk of bias  High risk of bias  Low risk of bias  Some concerns  Some concerns  \n Legend: Green = Yes or Possibly Yes, Yellow = Unclear, Red = No or Possibly No, Grey or Black = Not applicable  \n \n \n \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 20 of 24 \n Table 8. Risk of Bias Assessment of Case Series Studies Meeting Inclusion Criteria  \nSTUDY NAME  Aaby 2006  \nSIGNALING QUESTION  Nested case series  \nSelection   \nWere there clear criteria for inclusion in the case series?  Yes  \nWas the condition measured in a standard, reliable way for all \nparticipants included in the case series?  Possibly Yes  \nWere valid methods used for identification of the condition for \nall participants included in the case series?  Possibly No  \nDid the case series have consecutive inclusion of \nparticipants?  Yes  \nDid the case series have complete inclusion of participants?  No Information  \nWas there clear reporting of the demographics of the \nparticipants in the study?  No \nWas there clear reporting of clinical information of the \nparticipants?  No \nWere the outcomes or follow up results of cases clearly \nreported?  No Information  \nWas there clear reporting of the presenting site(s)/clinic(s) \ndemographic information?  No Information  \nAnalysis   \nWere appropriate statistical analyses used?  Yes  \nCOI   \nWere conflicts of interest disclosed and no obvious conflicts \nexist?  Possibly Yes  \nRisk -of-bias judgement  High risk of bias  \n Legend: Green = Yes or Possibly Yes, Yellow = Unclear, Red = No or Possibly No, Grey or Black = Not applicable  \n \n \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 21 of 24 \n E. Search Strategies and Results  \nTable 9. Primary Search of MEDLINE (OVID), Embase (OVID), CINAHL (Ebsco), Scopus, Cochrane Library  \nSearch Strategy:      \nDATABASE  STRATEGY  RUN DATE  RECORD \nCOUNT  \nMedline  \n(OVID)  \n1946 - 1. exp Hepatitis B Vaccines/  \n2. (((Hepatitis B OR HepB OR Hep B OR HBV) ADJ5 vaccin*) OR HepB -BD OR Engerix -B OR Recombivax HB).ti,ab,kf.  \n3. 1 OR 2  \n4. Exp Infant/  \n5. (Infant* OR newborn* OR new born* OR neonat* OR birth OR birth -dose*).ti,ab,kf.  \n6. 4 OR 5  \n7. Exp Safety/ OR exp Treatment Outcome/  \n8. (safety OR (vaccin* ADJ2 safe*) OR treatment outcome* OR adverse* OR harm OR harmful OR harms OR side effect* OR \nreaction*).ti,ab,kf. OR ae.fs  \n9. 7 OR 8  \n10. Exp Clinical Study/ OR exp Product Surveillance, Postmarketing/  \n11. (trial* OR observational stud* OR observation stud* OR clinical stud* OR surveillance OR reporting system* OR VAERS OR \npostmarket* OR post -market*).ti,ab,kf,hw.  \n12. 10 OR 11  \n13. 3 AND 6 AND 9 AND 12  07/31/2025  599 \nEmbase  \n(OVID)  \n1947 - 1. exp Hepatitis B Vaccine/  \n2. (((Hepatitis B OR HepB OR Hep B OR HBV) ADJ5 vaccin*) OR HepB -BD OR Engerix -B OR Recombivax HB).ti,ab,kf.  \n3. 1 OR 2  \n4. Exp Infant/  \n5. (Infant* OR newborn* OR new born* OR neonat* OR birth OR birth -dose*).ti,ab,kf.  \n6. 4 OR 5  \n7. Exp Safety/ OR exp Treatment Outcome/ OR adverse drug reaction/  \n8. (safety OR (vaccin* ADJ2 safe*) OR treatment outcome* OR adverse* OR harm OR harmful OR harms OR side effect* OR \nreaction*).ti,ab,kf. OR ae.fs  \n9. 7 OR 8  \n10. Exp Clinical Study/ OR exp Postmarketing Surveillance/  \n11. (trial* OR observational stud* OR observation stud* OR clinical stud* OR surveillance OR reporting system* OR VAERS OR \npostmarket* OR post -market*).ti,ab,kf,hw.  \n12. 10 OR 11  \n13. 3 AND 6 AND 9 AND 12  \n14. limit 13 to \"pubmed/medline\"  \n15. 13 NOT 14  \n16. limit 15 to conference abstract status  \n17. 15 NOT 16  07/31/2025  1527  \n \n- \nDUPLICATES  \n \n=165  \nUNIQUE \nRECORDS  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 22 of 24 \n DATABASE  STRATEGY  RUN DATE  RECORD \nCOUNT  \nCochrane \nLibrary  \n #1 [mh \"Hepatitis B Vaccines\"]  \n#2 (((\"Hepatitis B\":ti,ab,kw OR HepB:ti,ab,kw OR \"Hep B\":ti,ab,kw OR HBV:ti,ab,kw) NEAR/5 vaccin*:ti,ab,kw) OR HepB -\nBD:ti,ab,kw OR Engerix -B:ti,ab,kw OR \"Recombivax HB\":ti,ab,kw)  \n#3 #1 OR #2  \n#4 [mh Infant]  \n#5 (Infant*:ti,ab,kw OR newborn*:ti,ab,kw OR (\"new\" NEXT born*):ti,ab,kw OR neonat*:ti,ab,kw OR birth:ti,ab,kw OR birth -\ndose*:ti,ab,kw)  \n#6 #4 OR #5  \n#7 [mh Safety] OR [mh \"Treatment Outcome\"]  \n#8 (safety:ti,ab,kw OR (vaccin*:ti,ab,kw NEAR/2 safe*:ti,ab,kw) OR (\"treatment\" NEXT outcome*):ti,ab,kw OR \nadverse*:ti,ab,kw OR harm:ti,ab,kw OR harmful:ti,ab,kw OR harms:ti,ab,kw OR (\"side\" NEXT effect*):ti,ab,kw)  \n#9 #7 OR #8  \n#10 [mh ^\"Clinical Study\"] OR [mh ^\"Product Surveillance, Postmarketing\"]  \n#11 (trial*:ti,ab,kw OR (\"observational\" NEXT stud*):ti,ab,kw OR (\"observation\" NEXT stud*):ti,ab,kw OR (\"clinical\" NEXT \nstud*):ti,ab,kw OR surveillance:ti,ab,kw OR (\"reporting\" NEXT system*):ti,ab,kw OR VAERS:ti,ab,kw OR \npostmarket*:ti,ab,kw OR post -market*:t i,ab,kw)  \n#12 #10 OR #11  \n#13 #3 AND #6 AND #9 AND #12  \n 07/31/2025  400 \n \n- \nDUPLICATES  \n \n=145  \nUNIQUE \nRECORDS  \nCINAHL  \n(EBSCOHost)  S1 (MH \"Hepatitis B Vaccines+\")  \nS2 ((((TI \"Hepatitis B\" OR AB \"Hepatitis B\" OR SU \"Hepatitis B\") OR (TI HepB OR AB HepB OR SU HepB) OR (TI \"Hep B\" OR AB \n\"Hep B\" OR SU \"Hep B\") OR (TI HBV OR AB HBV OR SU HBV)) N5 (TI vaccin* OR AB vaccin* OR SU vaccin*)) OR (TI HepB -BD \nOR AB HepB -BD OR SU He pB-BD) OR (TI Engerix -B OR AB Engerix -B OR SU Engerix -B) OR (TI \"Recombivax HB\" OR AB \n\"Recombivax HB\" OR SU \"Recombivax HB\"))  \nS3 S1 OR S2  \nS4 (MH Infant+)  \nS5 ((TI Infant* OR AB Infant* OR SU Infant*) OR (TI newborn* OR AB newborn* OR SU newborn*) OR (TI \"new born*\" OR AB \n\"new born*\" OR SU \"new born*\") OR (TI neonat* OR AB neonat* OR SU neonat*) OR (TI birth OR AB birth OR SU birth) OR \n(TI birth -dose* OR AB birt h-dose* OR SU birth -dose*))  \nS6 S4 OR S5  \nS7 (MH Safety+) OR (MH \"Treatment Outcomes+\") OR (MH \"Adverse Drug Event+\")  \nS8 ((TI safety OR AB safety OR SU safety) OR ((TI vaccin* OR AB vaccin* OR SU vaccin*) N2 (TI safe* OR AB safe* OR SU safe*)) \nOR (TI \"treatment outcome*\" OR AB \"treatment outcome*\" OR SU \"treatment outcome*\") OR (TI adverse* OR AB \nadverse* OR SU adverse*) OR (TI harm OR AB harm OR SU harm) OR (TI harmful OR AB harmful OR SU harmful) OR (TI \nharms OR AB harms OR SU harms) OR (TI \"side effect*\" OR AB \"side effect*\" OR SU \"side effect*\"))  \nS9 S7 OR S8  \nS10 (MH \"Clinical Study+\") OR (MH \"Product Surveillance, Postmarketing+\")  \nS11 ((TI trial* OR AB trial* OR SU trial*) OR (TI \"observational stud*\" OR AB \"observational stud*\" OR SU \"observational stud*\") \nOR (TI \"observation stud*\" OR AB \"observation stud*\" OR SU \"observation stud*\") OR (TI \"clinical stud*\" OR AB \"clinical \nstud*\" OR S U \"clinical stud*\") OR (TI surveillance OR AB surveillance OR SU surveillance) OR (TI \"reporting system*\" OR AB 07/31/2025  22 \n \n- \nDUPLICATES  \n \n=7 \nUNIQUE \nRECORDS  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 23 of 24 \n DATABASE  STRATEGY  RUN DATE  RECORD \nCOUNT  \n\"reporting system*\" OR SU \"reporting system*\") OR (TI VAERS OR AB VAERS OR SU VAERS) OR (TI postmarket* OR AB \npostmarket* OR SU postmarket*) OR (TI post -market* OR AB post -market* OR SU post -market*))  \nS12 S10 OR S11  \nS13 S3 AND S6 AND S9 AND S12  \n \nLimiters  - Exclude  MEDLINE  records  \n \nF. References  \n \n1. Pittet L, Netea MG, Curtis N. Chapter 3 - Non -specific Effects of Vaccines. In: Stanley A. Plotkin WAO, Paul A. Offit, and Kathryn M. Edwards, ed. Plotkin's \nVaccines . 8 ed. Elsevier; 2023:37 -44.e7:chap 3.  \n2. Hosseini M -S, Jahanshahlou F, Akbarzadeh MA, Zarei M, Vaez -Gharamaleki Y. Formulating research questions for evidence -based studies. Journal of \nMedicine, Surgery, and Public Health . 2024/04/01/ 2024;2:100046. doi: https://doi.org/10.1016/j.glmedi.2023.100046  \n3. Guyatt G, Agoritsas T, Brignardello -Petersen R, et al. Core GRADE 1: overview of the Core GRADE approach. Bmj. Apr 22 2025;389:e081903. \ndoi:10.1136/bmj -2024 -081903  \n4. Aaby P, Jensen H, Walraven G. Age -specific changes in the female -male mortality ratio related to the pattern of vaccinations: An observational study \nfrom rural Gambia. Vaccine . 29 May 2006;24(22):4701 -4708. doi:10.1016/j.vaccine.2006.03.038  \n5. Aamand T, Fisker AB, Correia C, Fernandes M, Clipet -Jensen C, Thysen SM. Do Pentavalent (DTwP -Hib-HBV) vaccines have sex -differential nonspecific \neffects? An observational study. Observational Study  \nResearch Support, Non -U.S. Gov't. Hum Vaccin Immunother . 12 15 2023;19(3):2288297. doi:10.1080/21645515.2023.2288297  \n6. Fisker AB, Biering -Sorensen S, Lund N, et al. Contrasting female -male mortality ratios after routine vaccinations with pentavalent vaccine versus measles \nand yellow fever vaccine. A cohort study from urban Guinea -Bissau. Research Support, Non -U.S. Gov't. Vaccine . 08 31 2016;34(38):4551 -4557. \ndoi:10.1016/j.vaccine.2016.07.034  \n7. Fisker AB, Thysen SM. Non -live pentavalent vaccines after live measles vaccine may increase mortality. Research Support, Non -U.S. Gov't. Vaccine . 10 01 \n2018;36(41):6039 -6042. doi:10.1016/j.vaccine.2018.08.083  \n8. Garly ML, Jensen H, Martins CL, et al. Hepatitis B vaccination associated with higher female than male mortality in Guinea -Bissau: An observational \nstudy. Pediatr Infect Dis J . December 2004;23(12):1086 -1092. doi:10.1097/01.inf.0000145700.77286.94  \n9. Hanifi SMA, Biering -Sorensen S, Jensen AKG, Aaby P, Bhuiya A. Penta is associated with an increased female -male mortality ratio: cohort study from \nBangladesh. Research Support, Non -U.S. Gov't. Hum Vaccin Immunother . 01 02 2021;17(1):197 -204. doi:10.1080/21645515.2020.1763084  \n \nDisclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not be construed to represent any agency determination or \npolicy .  Page 24 of 24 \n 10. He WQ, Guo GN, Li C. The impact of hepatitis B vaccination in the United States, 1999 -2018. Hepatology . 06 2022;75(6):1566 -1578. \ndoi:10.1002/hep.32265  \n11. Morgan HJ, Nold MF, Kattan GS, et al. Hepatitis B vaccination of preterm infants and risk of bronchopulmonary dysplasia: a co hort study, Australia. \nVaccination contre l'hepatite B de prematures et risque de dysplasie bronchopulmonaire: etude de cohorte en  Australie, Vacunacion contra la hepatitis B en \nneonatos prematuros y riesgo de displasia broncopulmonar: estudio de cohortes en Australia. Bull World Health Organ . 2025;103(3):187 -193. \ndoi:10.2471/BLT.24.291683", "summary": "Disclaimer: The findings and conclusions herein are draft and have not been formally disseminated by the Centers for Disease Control and Prevention and should not  be construed to represent any agency determination or policy .  Page 1 of 24   ACIP BRIEFING MATERIALS FOR PUBLIC POSTING    The Non -specific Effects of Hepatitis B Vaccines : A Rapid Systematic Revie w  Table of Contents   A. Background  ................................ ................................…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-september-18-19-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-09-18-19/effects-hep-b-vax-summary-508.pdf", "doc_date": "2025-09-18", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 24}
{"title": "02 langer hep b 508", "content": "Hepatitis B Birth Dose Vaccination\nCDC Advisory Committee for Immunization Practices Meeting\nSeptember 18, 2025\n1U.S. Centers for Disease Control and Prevention\n\nPerinatal HBV transmission, which accounts for most infections globally, \nresults in severe health consequences.\nHBV = hepatitis B virus. Schillie S. MMWR Recomm Rep. 2018\n*Image(s) generated by ChatGPT 5.0 (OpenAI), August 2025. Content originated as data from scientific publications and was tra nsformed into an image via text prompts 2\n\nHepatitis B in the U.S. — a Tale of two Epidemiologies\n▪Up to 2.4 million persons estimated to have hepatitis B in \nthe United States1\n-50% unaware of their infection2\n▪Persons born outside the U.S.1,3\n-Chronic infection since childhood\n-Account for ~70% of all chronic infections\n▪14,400 estimated acute hepatitis B cases in the U.S. in 20234 \n-Unvaccinated persons with behavioral risk factors\n-Highest rates among adults aged 40 -59 years\n-Adults have higher clearance rates and lower risk for chronic infection5 \n1.Wong et al.  Hepatology 2021; 2. Bixler et al. Hepatol Commun. 2023; 3. Razavi -Shearer D, et al. The Lancet Regional Health Americas 2023;  4. \nhttps://www.cdc.gov/hepatitis -surveillance -2023/about/index.html ; 5. Chapter 10: Hepatitis B | Pink Book | CDC\nSource:  Razavi -Shearer D, et al. The Lancet Regional Health Americas 2023.  \nChronic HBV infection results in high lifetime healthcare costs.\n4Annual costs of treating a patient with less severe hepatitis B: $25,308 –$93,935 (2025 USD)\nAnnual cost of treating a patient requiring a liver transplant:  $174,282─$324,849 (2025 USD)\nHBV = hepatitis B virus\nNguyen MH, Burak Ozbay A, Liou I, Meyer N, Gordon SC, Dusheiko  G, Lim JK. Healthcare resource utilization and costs by disease severity in an insured national sample of US patients with ch ronic \nhepatitis B. J Hepatol. 2019 Jan;70(1):24 -32\nOriginal estimates converted from 2015 USD to 2025 USD using https://www.bls.gov/data/inflation_calculator.htm \n \nHepatitis B birth dose vaccination and immune globulin (HBIG) \nsubstantially reduce the risk of mother -to-child transmission. \n5Schillie S. MMWR Recomm Rep. 2018; Beasley RP et al. Lancet. 1983;  Lee C et al. 2006; Beasley RP et al. 1977; Armstrong GL. Pediatrics. 2001; \nMahoney. Pac Hth Dialog 1996; Ruff TA. The Journal of Infectious Diseases. 1995\n*Image(s) generated by ChatGPT 5.0 (OpenAI), August 2025. Content originated as data from scientific publications and was tra nsformed into an image via text promptsEARLIER BIRTH DOSE VACCINATION HAS \nGREATER EFF ECTIVENESS\nSetting Time after birth\nvaccinatedNumber of\nChildren% \nHBsAg+\nPalau> 3 days\n≤ 3 days30\n3236.7%\n0.6%\nMicronesia> 3 days\n≤ 3 days78\n2172.6%\n0.0%\nIndonesia> 7 days\n≤ 7 days656\n17173.0%\n1.4% \n\nHepatitis B vaccines\n•Two single -antigen hepatitis B vaccines are FDA -approved for use from \nbirth through adulthood; dosing varies by age group1\n-Recombivax HB (1986)\n-Engerix -B (1989)\n•Safety\n-The Institute of Medicine's Immunization Safety Review and the WHO's Global Advisory \nCommittee on Vaccine Safety concluded that hepatitis B vaccine is both safe and effective.1,2,3\n1.Poland GA et al, NEJM, 2004. 2. Stratton  K et al, Immunization Safety  Review , National Academies Press, 2002. 3. Global Advisory Committee on Vaccine Safety, Wkly  Epidemiol Rec, 2002.\n6\nHepatitis B vaccination is a multidose series, with \nincreasing seroprotection among infants after each dose. \n7\n•Hepatitis B vaccination recommendations on child and adolescent immunization schedule – United States, 2025\n•In addition to the immediate benefit of providing postexposure prophylaxis to the newborn, the \nhepatitis B birth dose serves as the first dose of the infant vaccination series.*\n•Among healthy infants, the 3 -dose hepatitis B vaccine series produces a protective antibody response \n(anti -HBs ≥10 mIU /mL) in approximately:\n•~25% of infants after the first dose, \n•~63% of infants after the second dose, and \n•~95% of infants after the third dose.\nhttps://www.cdc.gov/vaccines/hcp/imz -schedules/child -adolescent -age.html  (accessed 8/18/25); \n*Except for pre -term infants weighing <2,000 grams born to women known to be HBsAg positive.\nSchillie, S. et al. Prevention of Hepatitis B Virus Infection in the United States: Recommendations of the Advisory Committee  on Immunization Practices. MMWR Recomm Rep 67, 1 -31 (2018). \n8For decades, ACIP has recommended universal hepatitis B screening for pregnant women and \nbirth dose vaccination for infants born to women who are HBsAg(+) or HBsAg status unknown.\nACIP hepatitis B screening recommendations for pregnant women and\nperinatal postexposure recommendations for infants, United States\nModified from Bixler PHR 2023, Suppl Table 2. ACIP = Advisory Committee on Immunization Practices; HBIG = hepatitis B immune globulin; HepB , hepatitis B vaccine.  \n*Only single -antigen HepB  vaccine should be used for the birth dose.  Note:  All hepatitis B birth dose vaccinations are considered to be  the first dose of the infant series except among pre -term infants \nweighing <2,000 grams who are born to mothers who are HBsAg positive.\n1.CDC. MMWR Morb  Mortal Wkly  Rep 37, 341 -346, 351 (1988). 2.CDC. MMWR Morb  Mortal Wkly  Rep 33, 285 -290 (1984). 3. CDC. Update on hepatitis B prevention. MMWR Morb  Mortal Wkly  Rep 36, 353 -\n360, 366 (1987). 4.CDC. Recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR Recomm  Rep 40, 1 -25 (1991). 5. Schillie , S. et al. MMWR Recomm  Rep 67, 1 -31 (2018). \n6.  Mast, E. E. et al. MMWR Recomm  Rep 54, 1 -31 (2005). 7. Bixler D, et al. Public Health Rep. 2023 Jun 9\n\n9For decades, ACIP has recommended that the first dose of universal infant hepatitis B \nvaccination among infants born to HBsAg( -) women occur close to birth.\nACIP hepatitis B infant vaccination recommendations, United States\nModified from Bixler PHR 2023, Suppl Table 2. \nACIP = Advisory Committee on Immunization Practices; HBIG = hepatitis B immune globulin; HepB , hepatitis B vaccine.  \n*Only single -antigen HepB  vaccine should be used for the birth dose. \nNote:  All hepatitis B birth dose vaccinations are considered to be  the first dose of the infant series except among pre -term infants weighing <2,000 grams who are born to mothers who are HBsAg p ositive.\n1.CDC. MMWR Morb  Mortal Wkly  Rep 37, 341 -346, 351 (1988). 2.CDC. MMWR Morb  Mortal Wkly  Rep 33, 285 -290 (1984). 3. CDC. Update on hepatitis B prevention. MMWR Morb  Mortal Wkly  Rep 36, 353 -\n360, 366 (1987). 4.CDC. Recommendations of the Immunization Practices Advisory Committee (ACIP). MMWR Recomm  Rep 40, 1 -25 (1991). 5. Schillie , S. et al. MMWR Recomm  Rep 67, 1 -31 (2018). 6.  \nMast, E. E. et al. MMWR Recomm  Rep 54, 1 -31 (2005). 7. Bixler D et al. Public Health Rep. 2023 Jun 9\n\nHBV infections are missed among some pregnant women and \ncan result in catastrophic outcomes.\n10HBV = hepatitis B virus; PEP = post -exposure prophylaxis. \nSchillie et al. MMWR Recomm Rep. 2018 Jan 12;67(1):1 -31. \nWillis, B.C., et al., Pediatrics, 2010. 125(4): p. 704 -11.\nCDC. MMWR Morb Mortal Wkly Rep. 2001 Feb 16;50(6):94 -7. \nNolt D, et al. Pediatrics. 2022 Feb 1;149(2)\nMichigan, 1999\n“On December 14, 1999, a previously healthy 3 -month -old infant was admitted to a hospital with \ndiarrhea and jaundice, and acute hepatic failure attributed to HBV infection was diagnosed. The \ninfant died on December 17, 1999. The infant had not received her first dose of hepatitis B vaccine \nuntil age 2.5 months.\nThe infant's mother was found to be HBsAg -positive at the first of 10 prenatal visits. \nHowever, the prenatal -care record provided to the birth hospital indicated that the mother \nwas hepatitis -negative . Neither the provider nor the laboratory reported the mother's test results to \nMDCH as required by law.”\nThe Immunization Action Coalition documented \nmore than 500 transmissions of HBV in these \ntypes of situations from 1999 to 2002\nHepatitis B birth dose vaccination serves as a critical safety net against \ngaps in protection against perinatal HBV infection. \n11\nThe National Perinatal Hepatitis B Prevention \nProgram identifies less than half  of infants \nestimated to be born to HBV infected mothers\nKoneru et al. Pediatrics. 2021 Mar;147(3):e20201823.\nPham et al. Am J Prev Med. 2023 Jul;65(1):52 -59.\nKolasa  et al . Pediatr Infect Dis J. 2017 Jul;36(7):e175 -e180.\nMartin JA, Osterman MJK. Natl Vital Stat Rep. 2023 May;72(4):1 -14. PMID: 37252688.\nKoneru A, et al. Pediatrics. 2021 Mar;147(3):e20201823. \nImage(s) generated by ChatGPT 5.0 (OpenAI), August 2025. Content originated as data from scientific publications and was tran sformed into an image via text prompts\n\nUnvaccinated infants remain at risk of non -perinatal HBV acquisition. \n•HBV transmission occurs through percutaneous or mucosal exposure to infectious blood or body \nfluids\n•HBV can remain viable for over 7 days on environmental surfaces at room temperature.1 \n•Household and Community Transmission: Unvaccinated children living with a person with \nchronic HBV infection in a household or community setting are at risk for becoming infected.\n-Prior to HepB  BD, some U.S. -born children born to immigrant mothers without HBV infection had hepatitis \nB prevalences of 7 –11%2,3 attributable to community or household exposures. \n•In the United States, up to 2.4 M people are estimated to have hepatitis B4, and about 50% of \npeople with hepatitis B are unaware of their infection5.\n•Children who receive HepB  BD have higher rates of hepatitis B childhood vaccine series \ncompletion and had a positive impact on rates of being up to date for other age -appropriate \nvaccines 6,7,8\n12HBV = hepatitis B virus. HepB BD = hepatitis B birth dose vaccination. \n1. Bond et al, Lancet. 1981; 2. Franks et al, N Engl J Med. 1989; 3. Hurie et al, Pediatrics. 1992; 4. Wong et al, Hepatology. 2021; 5. Bixler et al, Hepatol ogy Communications; 2023. 6. Yusuf HR, et al, JAMA. 2000 \nAug 23 -30;284(8):978 -83 8; 7. Mast, E. E.  et al,  MMWR Recomm Rep  54, 1-31 (2005). 8. Mennito SH, Darden PM.. J Pediatr. 2010 Apr;156(4):618 -22.\nHepatitis B vaccination has been the cornerstone of hepatitis B control \nfor decades and has brought the U.S. within reach of elimination.\n05,00010,00015,00020,00025,00030,000\n1991\nUniversal infant\nhepatitis B\nvaccination\n1982\nRisk -based \nhepatitis B\nvaccination2005 \nUniversal infant \nvaccination prior to \nhospital discharge2018\nUniversal\ninfant hepatitis B\nvaccination \nwithin  24 hours\nof birth\n1991\nHepatitis B \nvaccination \nwithin 12 hours \nof birth for \ninfants born to \nwomen with \nunknown \nHBsAg status 2018  Hepatitis B vaccination and HBIG within 12 hours of \nbirth for infants born to women with unknown HBsAg status1988\nHepatitis B \nvaccination and \nHBIG within 12 \nhours of birth for \ninfants born to \nHBsAg (+) womenReported cases of acute hepatitis B and key ACIP vaccination recommendations among infants, United States, 1980 -2023\nHBIG = Hepatitis B immune globulin; CDC NNDSS Viral Hepatitis Surveillance  (https://www.cdc.gov/hepatitis/php/statistics -surveillance/index.html );\n†From 1991‒2010 all case classifications included (i.e., confirmed, probable, suspect, unknown); from 2011‒2023 only confirme d cases included \nBixler D, Roberts H, Panagiotakopoulos L, Nelson NP, Spradling PR, Teshale EH. Public Health Rep. 2023 Jun 9\nRescinding Universal HepB BD vaccination recommendations among infants born to HBsAg ( -) women \nmay result in more cases of perinatal HBV infection.\n14Potential Benefits of Rescinding \nUniversal HepB BD RecommendationsPotential Risks of Rescinding \nUniversal HepB BD Recommendations\nReductions in rare cases of hepatitis B birth dose \nvaccination adverse eventsIncreased cases of perinatal HBV transmission\nIncreased administrative complexity and failure points \nfor providers and health systems\nLack of safety net given gaps in access to prenatal care, \nHBV screening, and HBIG access\nDisproportionate harm to patients without insurance or \nlow healthcare engagement\nLower rates of hepatitis B childhood vaccine series \ncompletion\nHigher lifetime healthcare costs from missed \nopportunities to prevent and eliminate hepatitis B\nHepB BD = hepatitis B birth dose vaccination; adverse events listed in the section ‘Vaccine Safety’ in Schillie S. MMWR Recom m Rep. 2018 (page 11) \nRequest to CDC from ACIP Chair\n•Survey of HepB vaccine recommendations in developed countries, including \nthe United States, Canada, all EU countries, UK, Norway, Switzerland, \nIceland, Australia, New Zealand, South Korea and Japan. Specifically,   \n-At what age is the first dose recommended for: \n (i) children to HepB positive mothers, and for \n (ii) other children? \n-Also, in these countries, what is the prevalence of HepB infection in pregnant \nwomen?\n15\nGlobal hepatitis B birth dose vaccination policies\n16Hepatitis B vaccine birth dose vaccination policy by country, 20251\nUniversal HepB -BD:  \nHepatitis B vaccine recommended for all \nnewborns. \nSelective HepB -BD:  \nHepatitis B vaccine recommended only to \nnewborns born to HBsAg(+) women. \nPartially -Introduced Universal HepB -BD:  \nHepatitis B vaccine recommendations among \nnewborns varies by geographic location within \nthe country  (at least one jurisdiction \nrecommends universal HepB -BD). \nHepB -BD = hepatitis B birth dose vaccination. \n1. Provincial and territorial routine and catch -up vaccination schedule for infants and children in Canada - Canada.ca ; Hepatitis B vaccine – NHS ; Vaccine Scheduler | ECDC ; 9. Hepatitis B – Health \nNew Zealand | Te Whatu Ora ; Introduction of Hepatitis B vaccine ; Hepatitis B | The Australian Immunisation Handbook ; 20240220_Immunization_Schedule_english.pdf ; National Immunization \nProgram for children | Policy&Services : KDCA ; Hepatitis B\nHepatitis B first dose vaccination schedule in selected countries*\n17Sources: Provincial and territorial routine and catch -up vaccination schedule for infants and children in Canada - Canada.ca ; Hepatitis B vaccine – \nNHS ; Vaccine Scheduler | ECDC ; 9. Hepatitis B – Health New Zealand | Te Whatu Ora ;  The Australian Immunisation Handbook ; \n20240220_Immunization_Schedule_english.pdf ; National Immunization Program for children | Policy&Services : KDCA ; Hepatitis B* United States, Canada, all EU/EEA countries, UK, Norway, Switzerland, \nIceland, Australia, New Zealand, South Korea and Japan. Age at first dose Number of countries\nAt what age is the first dose recommended for children born to HBsAg (+) women?  (N=38)\nBefore discharge from the hospital, or within 24 hours of birth 36 \nIdeally within 24 hours of birth but no later than 7 days after birth 1 (Ireland)\nWithin 48 hours of birth (majority of newborns are vaccinated within 24 hours) 1 (Denmark)\nAt what age is the first dose recommended for children born to HBsAg ( -) women?\nCountries that provide a universal HepB -BD (N=8)\nSame schedule as children born to HBsAg (+) women 7\nIdeally within 24 hours but no later than 7 days after birth 1 (Australia)\nCountries that provide selective HepB -BD and universal infant hepatitis B vaccination policy (N=26)\nAt the age of 2 months 18\nAt the age of 3 months 6\nAt the age of 12 -13 years 1 (Hungary)\nVaries by province (2 months; 11 or 12 years) 1 (Canada)\nPrevalence of hepatitis B among pregnant women in selected countries*\n18Hepatitis B in England 2024 - GOV.UK ; Hepatitis B and C in Pregnancy and Children: A Canadian Perspective – PMC ; Evidence brief - prevention of hepatitis B and C in Europe and the UK ; Uptake of perinatal immunoprophylaxis for \ninfants born to women with a record of hepatitis B in Victoria (2009 –2017) – ScienceDirect ; Updated -National Hepatitis Elimination Profile - Switerland -July2023_0.pdf ; Gaps in Prenatal Hepatitis B Screening and Management of \nHBsAg Positive Pregnant Persons in the U.S., 2015 –2020 - PMC* United States, Canada, all EU/EEA countries, UK, Norway, Switzerland, Iceland, Australia, New Zealand, South Korea and Japa n. •Only 6 of 38 selected countries* have national registries to track hepatitis B screening in pregnant women and \nestimate prevalence on an annual basis\n•The remaining 32 countries (including the United States), do not have national registries to track hepatitis B \nscreening during pregnancy; when available, prevalence estimates from these countries are based on surveys or \nstudies.\n\nEU, UK and other countries with selective hepatitis B birth dose vaccination \nhave higher hepatitis B prenatal screening coverage than in the United States\n19EU = European Union; UK = United Kingdom.\n*No universal  healthcare coverage\n≠2023 data except for the following countries:  Lithuania, 2021; United States, 2015 -2019; France, Germany, and Poland, data >5 but <10 years old. \nNo data is publicly available for Austria, Belgium, Croatia, Cyprus, Greece, Iceland, Italy, Japan, Latvia, Lichtenstein, Lux emb ourg, Malta, New Zealand, Norway, Romania, South Korea, Spain, \nor Sweden. \nHepatitis B in England 2024 - GOV.UK ; Hepatitis B and C in Pregnancy and Children: A Canadian Perspective – PMC ; Evidence brief - prevention of hepatitis B and C in Europe and the UK ; Uptake of perinatal \nimmunoprophylaxis for infants born to women with a record of hepatitis B in Victoria (2009 –2017) – ScienceDirect ; Updated -National Hepatitis Elimination Profile - Switerland -July2023_0.pdf ; Gaps in Prenatal Hepatitis B Screening \nand Management of HBsAg Positive Pregnant Persons in the U.S., 2015 –2020 - PMCCoverage of antenatal screening for hepatitis B in selected countries≠\nRequest to CDC from ACIP Chair\n•Results from randomized trials concerning the administration of the HepB \nvaccine within 24 hours of birth, with all results stratified by the HepB \ninfection status of the mother. Include both efficacy data and adverse \nevents, including all -cause morbidity and mortality. For children whose \nmothers are HepB negative, present results for all children combined as \nwell as stratified by pre -mature birth and birth weight. If randomized data \nis lacking for any of the requested populations, please mention that.\n20\nSearch Results\n*Schillie SF, Murphy TV. Seroprotection after recombinant hepatitis B vaccination among newborn infants: a review. Vaccine. 2 013 May 17;31(21):2506 -16. doi: 10.1016/j.vaccine.2012.12.012. Epub 2012 Dec 17. 21Ordered Full -Text\n(n = 93)ESR Search\nJan 1987 -Dec 2011\n(n = 833)Existing Systematic Review (ESR)*Updated Rapid Systematic Review (URSR)\nOrdered Full -Text \n(n = 316)URSR Search\nDec 2011 -Aug 2025\n(n = 1390)\nDuplicates \n(n = 11)\nDid not meet \ninclusion \ncriteria \n(n=221)\nUnable to \nretrieve full -\ntext (n = 85)HepB Vaccination Studies\n(n = 47)\nIncluded in Original Review\n(n = 43)Not relevant/\nDuplicates \n(n = 740)\nNot relevant\n (n = 46)\nDuplicate \nsubjects\n(n = 4)\nIncluded in Update Review \n(n = 7)Did not meet \ninclusion \ncriteria for \nURSR \n(n = 36)HepB Birth Dose Studies\n(n = 10)Not relevant\n(n = 1063)Titles and Abstracts \nScreened\n(n = 1379)\nTotal Studies Included\n(n = 17)\nSummary of Cochrane risk of bias assessments* for studies in \nexisting and updated rapid systematic reviews (n=17)\n22\n \nD1 \n− \n− \n− \n+ \n− \n− \n− \n+ \n+ \n+ \nx \n+ \n− \nx \nx + \n+ \nD2 \n− \nx \nx + \n+ \n+ \n− \n− \n+ \n+ \n− \n− \n+ \n− \n− \n+ \n+ \nD3 \nx \n+ \n+ \n+ \n+ \n+ \n+ \n+ \n+ \n+ \n+ \nx \n+ \n+ \n+ \n+ \n+ \nD4 \nx \nx + \n+ \n+ \nx \nx + + \n+ \n+ \nx \n+ \n+ \n+ \n+ \n+ \nD5 \n− \n− \n+ \n+ \n+ \n− \n− \n− \nx \n+ \n+ \n− \n− \n− \n+ \n+ \n+ \nOverall  \nx \nx \nx + \n− \nx \nx \nx \nx − \nx \nx − \n− \nx \n+ \n− Study\nAssateerawatt (1993)\nBassily (1995)\nGorar (2024)\nHalliday (1992)\nHieu (2002)\nHieu (2015)\nKang (2015)\nLee (1995)\nPande (2013)\nSafadi (2021)\nTulenko (2024)\nVelu (2007)\nWang (2022)\nYang (2015)\nYerushalmi (1997)\nZhu (2016)\nZhu (2017)Domains:  \nD1: Bias due to randomization.  \nD2: Bias due to deviations from intended intervention.   \nD3: Bias due to missing data.  \nD4: Bias due to outcome measurement.  \nD5: Bias due to selection of reported result.High\nSome concerns\nLowJudgment of Risk of Bias\n*Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, Cates CJ, Cheng H -Y, Corbett MS, Eldridge SM, Hernán MA, Hope well S, Hróbjartsson A, Junqueira DR, Jüni P,  Kirkham JJ, Lasserson T, \nLi T, McAleenan A, Reeves BC, Shepperd S, Shrier I, Stewart LA, Tilling K, White IR, Whiting PF, Higgins JPT. RoB 2: a revise d tool for assessing risk of bias in randomised trials. BMJ 2019; 366: l4898.\nIntervention Characteristics (n=17)\nAbbreviations: µg, micrograms; HBIG hepatitis B immune globulin \n*Not mutually exclusive  \n23Characteristic # of Studies Reporting (%)\nIntervention Study Type Efficacy trials 2 (11.8%)\nTiming of vaccination 1 (5.9%)\nProduct or formulation differences 8 (47.1%)\nDose and schedule 4 (23.5%)\nHBIG co -intervention 2 (11.8%)\nVaccine Administered* Engerix 7 (41.2%)\nRecombivax 1 (5.9%)\nOther 14 (82.3%)\nVaccine Dose* 10 µg 13 (76.4%)\n20 µg 2 (5.9%)\nOther 6 (35.2%)\nVaccination Schedule 0, 1, 6 months 11 (64.7%)\n0, 1, 2, 12 months 1 (5.9%)\nOther 5 (29.4%)\nEfficacy Trials (n=2)\nHepatitis B vaccine series first administered at birth achieved high levels of seroprotection .\nAbbreviations: HBeAg , hepatitis B virus e -antigen; HBsAg, hepatitis B surface antigen; mcg, micrograms\nSeroprotection : Anti-HBs ≥10 mIU /mL at least 1 -2 month after the final dose in the vaccine series or between 9 -12 months of age. \n24Author (year)Comparison \nArmsMaternal \nStatusSeroprotection\n% Difference Risk of Bias Intervention Comparator\nHieu (2002) Hepavax vs. \nEngerixHBsAg positive 49/52 (94.2%) 45/52 (86.5%) 7.7 pct pts Some concernAuthor (year)Comparison \nArmsMaternal \nStatusSeroprotection\n% Difference Risk of Bias\nIntervention Comparator\nAssateerawatt \n(1993)20 mcg + \nHBIG vs. \n20mcgHBsAg positive and \nHBeAg positive26/26 (100%) 22/23 (95.7%) 4.3 pct pts HighHepB vaccine \nComparative efficacy\nEfficacy Trials (n=2)\nAmong infants born to HBsAg positive mothers, h epatitis B birth dose vaccine \ndemonstrated efficacy  in the prevention of perinatal transmission. \nAbbreviations: HBeAg , hepatitis B virus e -antigen; HBsAg, hepatitis B surface antigen; mcg, micrograms \n*Vaccine refusals 25Author (year)Comparison \nArmsMaternal \nStatusInfant HBsAg Positive  Cases\nRisk Ratio (95% CI) Risk of Bias Intervention Comparator\nHieu (2002) Hepavax vs. \nEngerixHBsAg positive 1/53 (1.9%) 2/52 (3.8%) 0.49 (0.05, 5.25) Some concernsAuthor (year)Comparison \nArmsMaternal \nStatusInfant HBsAg Positive Cases\nRisk Ratio (95% CI) Risk of Bias\nIntervention Comparator\nAssateerawatt \n(1993)20 mcg vs. \nno vaccine*HBsAg positive and \nHBeAg positive3/22 (13.6%) 34/40 (85.0%) 0.16 (0.06, 0.46) High\nAssateerawatt \n(1993)20 mcg + \nHBIG vs. no \nvaccine*HBsAg positive and \nHBeAg positive1/25 (4.0%) 34/40 (85.0%) 0.05 (0.01, 0.32) HighHepB vaccine vs. no vaccine*\nComparative efficacy\nEfficacy Trial (n=1)\nHepatitis B birth dose resulted in few systemic adverse events .\nAbbreviations: HBeAg, hepatitis B virus e -antigen; HBsAg, hepatitis B surface antigen; mcg, micrograms\n26Author (year)Comparison \nArmsMaternal StatusSystemic Adverse Events\nRisk Ratio (95% CI) Risk of Bias Intervention Comparator\nHieu (2002) Hepavax vs. \nEngerixHBsAg positive 2/53 (3.8%) 2/52 (3.9%) 0.98 (0.14, 6.71) Some \nconcernsComparative efficacy\nNote: majority of adverse events were reported as mild fever\nTiming of Vaccination Trial (n=1)*\nAmong infants born to HBsAg negative mothers, high level of seroprotection  and no significant \ndifference in adverse events  reported between the intervention and comparison groups. \n•Intervention: received 2.5 µg Recombivax vaccine at birth, 2 months, and 6 months\n•Comparator:  received 3 doses of 2.5 µg Recombivax vaccine seroprotection  at the end of the study, starting at 18 \nmonths\n•Maternal status: HBsAg negative\n•Risk of bias assessed: High\n•Outcomes:\n-Seroprotection : \n•91.0% (162/178) of intervention group achieved seroprotection  1 month after the final dose of the vaccine series \n-Adverse events : \n•Localized symptoms: I: 5/178 (2.8%); C: 3/191 (1.6%) → RR = 1.77 (95% CI: 0.43, 7.29); RD = 1.2%\n•Systemic symptoms: I: 10/178 (5.6%); C: 4/191 (2.1%) → RR = 2.59 (95% CI: 0.83, 8.12); RD = 3.5% \n•Summary: \n-Over 9 in 10 newborn infants in the intervention group achieve seroprotection . \n-Among infants born to HBsAg negative mothers, there was no significant difference in adverse events reported between the \nintervention and comparison groups. \nAbbreviations: C, comparison group; HBsAg, hepatitis B surface antigen; I, intervention group; RR, risk ratio; RD, risk diffe rence (absolute)\n*Bassily ,​ S.,​Kotkat ,​ A.,​Gray,​ G.,​Hyams,​ K. C.,​Brown,​ F. M.,​Imam,​ I. Z.,​Arthur,​ R.. Comparative study of the immunogenicity and safety  of two dosing schedules of hepatitis B vaccine in neonates. Am J Trop Med Hyg. 1995. 53:419 -22. 27\nProduct or Formulation Trials \nHepatitis B vaccine series beginning at birth among infants born to HBsAg positive or negative women\n•Seroprotection  (n=7)\n-Achieved high levels  of seroprotection  among infants in both intervention (89% -99%) and comparison groups (71% -98%).\n•Efficacy  (n=4)\n-Among HBsAg positive women, demonstrated equivalent efficacy in the prevention of perinatal transmission between \nintervention and comparison groups\n•Adverse events (n=5)\n-Hepatitis B birth dose resulted in few local or systemic adverse events among infants in intervention and comparison groups\n28Seroprotection studies: Halliday, 1992; Hieu, 2015; Safadi, 2021; Velu, 2007; Yerulshami, 1997; Zhu, 2016; Zhu 2017. \nEfficacy studies: Halliday, 1992; Velu, 2007; Safadi, 2021; Zhu 2017. \n*Local symptoms may include injection site pain, soreness, redness, swelling in the arm where the shot was given; alternative ly, investigators may report under a general grouping of “local adverse events”. \nSystemic symptoms may include fever, excessive crying, rash, irritability, vomiting, diarrhea, loss of appetite, drowsiness; alternatively, investigators may report under a general grouping of “systemic adverse events”.\nLocal Symptoms (n=5) Systemic Symptoms (n=4)\n\nDose and Schedule Trials (n=4) \nAmong infants born to HBsAg positive or negative women, \nhepatitis B birth dose vaccine schedule is seroprotective\n29Author (year) Comparison Arms Maternal StatusSeroprotection\nPercent \ndifferenceRisk of Bias Intervention Comparator\nLee (1995) 5 mcg vs. 2.5 mcg HBsAg negative 261/279 (94.0%) 271/308 (88.0) 6.0 pct pts High\nKang (2015) 10 mcg vs. 5 mcg All negatives + \npositives169/177 (95.5%) 166/173 (96.0%) -0.5 pct pts High\nTulenko \n(2024)4 doses vs. 3 \ndosesHBsAg negative 24/28 (85.7%) 26/28 (93.0%) -7.3 pct pts High\nGorar (2024) HepB BD vax vs. \nstandard schedule \n(no BD)HBsAg negative 116/121 (96.0%) 57/97 (59.0%) 37.0 pct pts High\nDose and Schedule Trials (n=2) \nAmong infants born to HBsAg positive or negative women, \nhepatitis B birth dose vaccine schedule has high efficacy\n30Author (year)Comparison \nArmsMaternal \nStatusInfant HBsAg Positive  Cases\nRisk Ratio (95% CI) Risk of Bias Intervention Comparator\nKang (2015) 10 mcg vs. \n5 mcgAll negatives \n+ positives4/90 (4.4%) 6/90 (6.7%) 0.67 (0.19, 2.28) High\nTulenko (2024) 4-dose \nseries vs. 3 -\ndose seriesHBsAg \nnegative0/28 0/28 1.00 (0.02, 48.7) High\nDose and Schedule Trials: Safety Outcomes (n=1) \nAmong infants born to HBsAg positive or negative women, \nhepatitis B birth dose vaccine schedule resulted in few local or systemic adverse events\n31Author (year)Comparison \nArmsMaternal StatusLocal Adverse Events\nRisk Ratio (95% CI) Risk of Bias Intervention Comparator\nKang (2015) 10 mcg vs. 5 \nmcgAll negatives + \npositives1/253 (0.4%) 2/253 (0.8%) 0.50 (0.05, 5.48) High\nAuthor (year)Comparison \nArmsMaternal StatusSystemic Adverse Events\nRisk Ratio (95% CI) Risk of Bias Intervention Comparator\nKang (2015) 10 mcg vs. 5 \nmcgAll negatives + \npositives8/253 (3.2%) 7/253 (2.8%) 1.14 (0.42, 3.10) High\nEvidence Gap / Limitations\nEvidence Gap:\n•Lack of placebo -controlled trials assessing efficacy \n-This is not surprising as it is unethical to withhold a proven, safe and effective intervention (i.e., hepatitis B \nvaccination) simply to include a placebo group \n•Paucity of evidence reporting outcomes for preterm/LBW/ELBW infants, as well as morbidity and \nmortality for all infants\nLimitations:\n•Heterogeneous reporting of timepoints and definitions\n•Many of the studies were done before the wide application of the CONSORT statement*, which seeks to \nimprove reporting of randomized controlled trials (RCTs)\n•Most of the RCTs (59%) assessed had a high risk of overall bias primarily due to the randomization and \nmeasurement of outcomes     \nAbbreviations:  LBW, low birth weight; ELBW, extremely low birth weight.\n*Hopewell S, Chan A, Collins GS, et al. CONSORT 2025 Statement: Updated Guideline for Reporting Randomized Trials. JAMA. 2025 ;333(22):1998 –2005. doi:10.1001/jama.2025.434732\nConclusion\n•Based on the included body of evidence:\n \n-Hepatitis B birth dose induces high seroprotection  and efficacy\n-Hepatitis B birth dose vaccine is safe \n-Head -to-head comparisons of various hepatitis B recombinant vaccine products, \ndoses, and schedule show no meaningful differences in reported outcomes in \nefficacy and safety\n33\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    cdc.gov\nFollow us on X (Twitter) @CDCgov & @CDCEnvironment\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position \nof the U. S. Centers for Disease Control and Prevention.\n34\nBackground Slides\n35\nSearch for Evidence\n•Identified an existing systematic review focused \non HepB vaccination among newborns*\n-Used the Schillie review as a starting point\n-Search period:  1/1/1987 – 12/16/2011\n•Conducted an updated rapid systematic review \nusing a similar search strategy\n-Search period: 12/17/2011 – 8/14/2025\n•Electronic databases searched:\n-Medline (OVID)\n-Embase (OVID) \n36\n*Schillie SF, Murphy TV. Seroprotection after recombinant hepatitis B vaccination among newborn infants: a review. Vaccine. 2 013 May 17;31(21):2506 -16. \nExisting Systematic Review*\n•Objective: To summarize seroprotection  and immunogenicity of recombinant hepatitis B  \nvaccines administered within the first 30 days of life\n•Search Period: January 1, 1987  to December 16, 2011\n•Databases: Medline (via PubMed) and Embase (OVID)\n•Key Inclusion Criteria: studies reporting seroprotective response to monovalent recombinant \nHepB  vaccine administered to infants within ≤30 days\n•Key Exclusion Criteria:\n-When seroprotection  was assessed in conjunction with administration of other vaccines\n-When a combination vaccine containing hepatitis B vaccine was administered\n-When vaccine was not administered intramuscularly \n-When seroprotection  was not reported within 3 months of the final dose\n37*Schillie SF, Murphy TV. Seroprotection after recombinant hepatitis B vaccination among newborn infants: a review. Vaccine. 2 013 May 17;31(21):2506 -16. \nUpdated Rapid Systematic Review:  Inclusion/Exclusion Criteria\n38Inclusion Criteria Exclusion Criteria\n• Newborn infants receiving a HepB vaccine at birth                               \n(i.e., ≤24 hours old at dose 1)• Non -English language articles\n• Animal studies\n• Randomized controlled trial\n• Monovalent HepB vaccine administered within ≤24 hours of birth; \nco-administration of HepB immune globulin (HBIG) is permitted• Combination infant vaccines at birth, when the HepB  component’s \ncontribution or timing cannot be isolated\n• No extractable data on maternal status; for HBsAg( -) mothers, no \ndata for total group and none for prematurity/birth -weight strata\n• No outcome of interest reported \n• Results not stratified by intervention arm\n• Provided comparative data regarding the safety and effectiveness of \nHep immunization strategies, such as delayed HepB vaccination \n(>24 hrs. after birth) or no HepB vaccination; other vaccination \nschedule• Nonrandomized/observational designs; RCTs where all arms initiate \nvaccine >24 hours after birth without a ≤24 -hour comparator\n•Outcomes include any of the following:\n•HBV infection \n•Chronic HBV infection \n•Seroprotection\n•Seroconversion\n•Safety outcomes \n•All-cause morbidity\n•All-cause mortality• Preprints\n• Conference abstracts\n• Editorial/Commentary\n• Letter to the Editor\nList of Outcomes\n*Local symptoms may include injection site pain, soreness, redness, swelling in the arm where the shot was given. Alternative ly, investigators may report under a \ngeneral grouping of “local adverse events”; systemic symptoms may include fever, excessive crying, rash, irritability, vomiti ng, diarrhea, loss of appetite, drowsiness. \nAlternatively, investigators may report under a general grouping of “systemic adverse events.”\n39Outcome Type Outcome Definition Included in ESR? Included in URSR?\nEfficacy • HBsAg and/or HBV DNA positivity Yes Yes\nSeroprotection • Anti-HBs ≥10 mIU/mL at least 1 -2 \nmonth after the final dose in the \nvaccine series or between 9 -12 \nmonths of age.Yes Yes\nSafety • Local/systemic adverse events* Yes Yes\nMorbidity • Severe illness \n• HospitalizationN/R Yes\nMortality • Death N/R Yes\nAbbreviations: anti -HBs, antibody to hepatitis B surface antigen; ESR, existing systematic review; URSR, updated rapid systemati c review; HBsAg, hepatitis B \nsurface antigen; HBV DNA, hepatitis B virus deoxyribonucleic acid. N/R = not reported \nRisk of Bias Assessment\n•Cochrane Risk of Bias, version 2 (RoB 2) 1\n-Used to assess risk of bias in RCTs\n•Bias related to:\n–randomization process\n–Deviation from intended intervention\n–Missing outcome data\n–Measurement of outcome\n–Selection of reported results\n-RoB 2 overall judgement options: low risk, some concerns, high risk \n40\n1Sterne JAC, Savović J, Page MJ, Elbers RG, Blencowe NS, Boutron I, Cates CJ, Cheng H -Y, Corbett MS, Eldridge SM, Hernán MA, Hope well S, Hróbjartsson A, Junqueira DR, Jüni P,  Kirkham JJ, Lasserson T, \nLi T, McAleenan A, Reeves BC, Shepperd S, Shrier I, Stewart LA, Tilling K, White IR, Whiting PF, Higgins JPT. RoB 2: a revise d tool for assessing risk of bias in randomised trials. BMJ 2019; 366: l4898.\nAnalyses and Presentation Decisions\n41Factor Decision\nType  of Analysis Proportions for seroprotection; risk ratios for efficacy and safety outcomes\nTime  Point UsedSeroprotection:  first reported time point immediately following the last dose in \na series\nEfficacy (against HBV infection) : latest  available time point with ongoing \nintervention\nSafety outcomes:  at birth or the closest time point immediately after the birth \ndose\nOutcome Measure Multiple outcome measures reported separately\nOverall Effect Estimate Measure Pooled random effect meta -analysis where possible\nMultiple Intervention  Arms Intervention  arms reported separately\nSummary Qualitatively  compare summary estimates\nAbbreviations: HBV, hepatitis B virus \nSearch Strategy: Medline (OVID)\n421.exp Hepatitis B Vaccines/\n2.(((Hepatitis B OR HepB OR Hep B OR HBV) ADJ5 vaccin*) OR HepB -BD OR Engerix -B OR Recombivax \nHB OR Hepavax -Gene).ti,ab,kf.\n3.1 OR 2\n4.Exp Infant/\n5.(Infant* OR newborn* OR new born * OR neonat* OR birth OR birth -dose*).ti,ab,kf.\n6.4 OR 5\n7.Hepatitis B/im OR Hepatitis B Antibodies/ OR Hepatitis B Surface Antigens/ \n8.(seroprotection OR sero -protection OR immunogeni* OR immune response OR antibod*).ti,ab,kf.\n9.7 OR 8\n10.Randomized Controlled Trials as Topic/\n11.(random* OR RCT* OR clinical trial* OR clinical stud* OR controlled trial* OR double -blind* OR \nsingle -blind* OR placebo* OR control group*).ti,ab,kf,hw.\n12.10 OR 11\n13.3 AND 6 AND 9 AND 12\n14.exp animals/ NOT exp humans/\n15.13 NOT 14\n16.limit 15 to dt=\"20111217 -20250814\"\n17.limit 16 to English language\nSearch Strategy: Embase (OVID)\n1.exp Hepatitis B Vaccine/\n2.(((Hepatitis B OR HepB OR Hep B OR HBV) ADJ5 vaccin*) OR HepB -BD OR Engerix -B OR Recombivax HB OR Hepavax -\nGene).ti,ab,kf.\n3.1 OR 2\n4.Exp Infant/\n5.(Infant* OR newborn* OR new born * OR neonat* OR birth OR birth -dose*).ti,ab,kf.\n6.4 OR 5\n7.Hepatitis B Antibody/ OR Hepatitis B Surface Antigen/ \n8.(seroprotection OR sero -protection OR immunogeni* OR immune response OR antibod*).ti,ab,kf.\n9.7 OR 8\n10.\"randomized controlled trial (topic)\"/ \n11.(random* OR RCT* OR clinical trial* OR clinical stud* OR controlled trial* OR double -blind* OR single -blind* OR placebo* OR \ncontrol group*).ti,ab,kf,hw.\n12.10 OR 11\n13.3 AND 6 AND 9 AND 12\n14.exp animal/ NOT exp human/\n15.13 NOT 14\n16.limit 15 to dc=\"20111217 -20250814\"\n17.limit 16 to English language\n43\nList of Included Studies (n=17), Part I\n44References Latest Follow -\nup Period \n(months)Sample \nSize\n• Assateerawatt , A.,Tanphaichitr , V. S., Suvatte , V.,Yodthong , S..  Immunogenicity and efficacy of a recombinant DNA hepatitis B vaccine, \nGenHevac  B Pasteur in high risk  neonates, school children and healthy adults. Asian Pac J Allergy Immunol.  1993. 11:85 -91.12 100\n• Bassily , S.,Kotkat , A.,Gray , G.,Hyams , K. C.,Brown , F. M.,Imam , I. Z.,Arthur , R..  Comparative study of the immunogenicity and safety of two \ndosing schedules of hepatitis B vaccine in neonates. Am J Trop Med Hyg.  1995. 53:419 -22.18 590\n• Gorar , Z. A.,Butt , Z. A..  Impact of hepatitis B birth dose on immune response in Pakistani children: an open -label, non -inferiority \nrandomized controlled trial, implications for achieving SDG target. Infectious Diseases.  2024. 56:1 -10 .5 296\n• Halliday, M. L.,Kang , L. Y.,Rankin , J. G.,Coates , R. A.,Corey , P. N.,Hu , Z. H.,Zhou , T. K.,Yuan , G. J.,Yao , F. L..  An efficacy trial of a mammalian \ncell-derived recombinant DNA hepatitis B vaccine in infants born to mothers positive for HBsAg, in Shanghai, China. Int J Epidem iol.  1992. \n21:564 -73.12 220\n• Hieu, N. T.,Kim , K. H.,Janowicz , Z.,Timmermans , I..  Comparative efficacy, safety and immunogenicity of Hepavax -Gene and Engerix -B, \nrecombinant hepatitis B vaccines, in infants born to HBsAg and HBeAg  positive mothers in Vietnam: an assessment at 2 years. Vaccine.  \n2002. 20:1803 -8.24 105\n• Hieu, N. T.,Sarnecki , M., Tolboom , J..  The safety and immunogenicity of two hepatitis B vaccine formulations (thiomersal -free and \nthiomersal -containing) in healthy vietnamese  infants: a phase III, prospective, single -blinded, randomized, controlled trial. Pediatric \nInfectious Disease Journal.  2015. 34:79 -83.7 408\n• Kang, G.,Ma , F.,Chen , H.,Yang , Y.,Guo , S.,Wang , Z.,Liang , X.,Li, L.,Cui , F.,Zhang , L..  Efficacy of antigen dosage on the hepatitis B vaccine \nresponse in infants born to hepatitis B -uninfected and hepatitis B -infected mothers. Vaccine.  2015. 33:4093 -9.   6 506\n• Lee, S. S.,Lo , Y. C.,Young , B. W.,Wong , K. H.,Lim , W. L..  A reduced dose approach to hepatitis B vaccination for low -risk newborns and \npreschool children. Vaccine.  1995. 13:373 -6.12 587\n• Pande C, Sarin SK, Patra S, Kumar A, Mishra S, Srivastava S, et al. Hepatitis B vaccination with or without hepatitis B immun oglobulin at \nbirth to babies born of HBsAg -positive mothers prevents overt HBV transmission but may not prevent occult HBV infection in babie s: a \nrandomized controlled trial. J Viral Hepat . 2013 Nov;20(11):801 -10.24 259\nList of Included Studies ( n=17), Part II\n45References Latest Follow -up \nPeriod (months)Sample Size\n•Safadi, R.,Khoury , T.,Saed , N.,Hakim , M.,Jamalia , J.,Nijim , Y.,Farah , N.,Nuser , T.,Natur , N.,Mahamid , M.,Amer , J.,Roppert , P. L.,Gerlich , \nW. H.,Glebe , D..  Efficacy of Birth Dose Vaccination in Preventing Mother -to-Child Transmission of Hepatitis B: A Randomized \nControlled Trial Comparing Engerix -B and Sci -B-Vac. Vaccines.  2021. 9:01.12 171\n•Tulenko, S. E.,Ngimbi , P.,Mwandagalirwa , K.,Tabala , M.,Matondo , J.,Ntambua , S.,Mbonze , N.,Mbendi , C.,Luhata , C.,Jhaveri , \nR.,Edwards , J. K.,Becker -Dreps, S.,Moormann , A. M.,Kaba , D.,Yotebieng , M.,Parr , J. B.,Gower , E. W.,Thompson , P..  Immunogenicity of \na Birth Dose of Hepatitis B Vaccine in Kinshasa, Democratic Republic of Congo: A Randomised , Controlled Trial. Journal of Viral \nHepatitis.  2024. 31:795 -807.12 231\n•Velu, V.,Nandakumar , S.,Shanmugam , S.,Jadhav , S. S.,Kulkarni , P. S.,Thyagarajan , S. P..  Comparison of three different recombinant \nhepatitis B vaccines: GeneVac -B, Engerix  B and Shanvac  B in high risk  infants born to HBsAg positive mothers in India. World J \nGastroenterol.  2007. 13:3084 -9. 12 158\n•Wang, H.,Fang , J. W.,Gu , Z. W.,Song , D. J.,Chen , Y.,Chen , G. D.,Zhao , B.,Sun , C.,Ma , Y.,Wang , K. X.,Shen , J. Q.,Yang , X. F.,Luo , Q..  \nApplication of hepatitis B immunoglobulin in prevention of mother -to-child transmission of chronic hepatitis B in HBsAg - and HBeAg -\npositive mother. Journal of Obstetrics & Gynaecology .  2022. 42:877 -882.6 331\n•Yang, S.,Ma , X.,Ni , H.,Zhou , S.,Hu , D.,Shi , H.,Chen , X.,Dong , H.,Xu , G..  Safety, immunization coverage and determinants of a new kind \nof Hepatitis B vaccine firstly applied in Ningbo, China. Human vaccines & Immunotherapeutics.  2015. 11:2819 -26.6 8556\n•Yerushalmi, B.,Raz , R.,Blondheim , O.,Shumov , E.,Koren , R.,Dagan , R..  Safety and immunogenicity of a novel mammalian cell -derived \nrecombinant hepatitis B vaccine containing Pre -S1 and Pre -S2 antigens in neonates. Pediatr  Infect Dis J.  1997. 16:587 -92.12 205\n•Zhu, F. C.,Sun , K. X.,Pan , H. X.,Yang , Z. H.,Lu , Y.,Liang , Z. L.,Liang , X. F.,Wang , F. Z.,Zeng , Y.,Li, J..  The immunogenicity in healthy infants \nand efficiency to prevent mother to child transmission of Hepatitis B virus of a 10mcg recombinant yeast -derived Hepatitis B vac cine \n(Hep -KSC). Vaccine.  2016. 34:2656 -62.6 1731\n•Zhu, F., Deckx , H.,Roten , R.,Michiels , B.,Sarnecki , M..  Comparative Efficacy, Safety and Immunogenicity of Hepavax -Gene TF and \nEngerix -B Recombinant Hepatitis B Vaccines in Neonates in China. Pediatric Infectious Disease Journal.  2017. 36:94 -101.12 1739", "summary": "Hepatitis B Birth Dose Vaccination CDC Advisory Committee for Immunization Practices Meeting September 18, 2025 1U.S. Centers for Disease Control and Prevention  Perinatal HBV transmission, which accounts for most infections globally,  results in severe health consequences. HBV = hepatitis B virus. Schillie S. MMWR Recomm Rep. 2018 *Image(s) generated by ChatGPT 5.0 (OpenAI), August 2025. Content originated as data from scientific publications and was tra nsformed into an image via text…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-september-18-19-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-09-18-19/02-langer-hep-b-508.pdf", "doc_date": "2025-09-18", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 45}
{"title": "02 su hep b 508", "content": "A Review of the Safety of Hepatitis B Birth Dose \nVaccination\nJohn Su\nActing Director\nImmunization Safety Office\nCenters for Disease Control and Prevention\nSeptember 18, 2025National Center for Emerging and Zoonotic Infectious Diseases\nRequest to CDC from ACIP Chair\nSafety data for HepB administration within 24 hours of birth from CDC’s \nVaccine Safety Datalink and from FDA’s Biologics Effectiveness and Safety \nSystem. Include (i) mild and serious adverse events; (ii) all cause morbidity and mortality; (iii) short term and long -term safety; (iv) both \nspecific outcomes of pre- determined concern as well as results from data \nmining where large numbers of potential adverse events are evaluated; and (v) both combined results and results stratified by sex. If some of these types of safety studies are unavailable, please mention that.\n2\nRapid systematic review of hepatitis B post- licensure \nsafety data\n•Key question:\n-What is the safety of the hepatitis B \nvaccine administered within the first 30 days of life?\n•Conducted a new rapid systematic review of published literature\n-Search conducted July 31, 2025 with no \ndate restrictions for publications\n•Electronic databases searched:\n-MEDLINE\n-EMBASE \n-CINAHL\n-Cochrane \n* Population, Intervention, Comparator, and Outcome, Setting, Time frameworkPI/ECO(ST) \nELEMENT*Description for this Review\nPopulation Neonates, Newborns, Infants\nIntervention or ExposureHepatitis B vaccine administration within the \nfirst 30 days of birth:\nHepB, HepB -BD, HBV, Engerix -B, Recombivax \nHB\nComparator (if \napplicable)Any or none\nOutcome(s) Adverse events\nAdverse outcomesSafety outcomesSide effects\nReaction\nAdverse reactionAdverse effectSerious adverse event\nSetting Any\nTime Frame Any publication years\nAny duration of follow up  Search Strategy\n3\nRapid systematic review:  \nInclusion/exclusion criteria\nInclusion Criteria Exclusion Criteria\n•Newborn infants receiving a hepatitis B vaccine \nat birth (i.e., ≤30 days old at dose 1)•Non -English language articles\n•Animal studies\n•Randomized control trial (RCT)\n•Observational studies\n•Case series ≥ 10\n•Data from surveillance systems•Any population that did not receive hepatitis B vaccine at ≤30 days old at dose 1\n•N < 10\nOutcomes include any of the following:•Safety\n•Adverse events\n•Serious adverse events\n•Side effects•Clinical trial protocols\n•(e.g., clinicaltrials.gov, trialsearch.gov identified in the citation)\n•Conference abstracts/ posters\n•Conference proceedings in title or journal title\n•Title starts with a number\n•Poster\n4\nResults\nResults of rapid systematic review of hepatitis B safety \nadministered in the first 30 days of life\nIdentification Screening IncludedStudies from databases/registers (n = 1916)\nMEDLINE (n = 1916)Studies  removed (n = 9)  \nDuplicates identified manually (n = 9)\nDuplicates identified by Covidence (n = 0) \nMarked as ineligible by automation tools (n = 0)\nOther reasons (n = 0)\nStudies screened  at title & abstract (n = 1907) Studies excluded  at title & abstract (n = 1678)\nDid not meet inclusion criteria (n = 1678)\nStudies assessed for eligibility  at full text \nreview          (n = 229)    Studies excluded  at full text review (n = 158)  \nNo intervention of interest (n = 48)\nNo outcome of interest (n = 30)\nNot relevant to key question (n = 7)No population of interest (n = 51)Not available in English (n = 5)\nInsufficient methodologic reporting (i.e., poster, abstract, letter to editor) (n = 8)\nNo primary data collection or secondary data not systematically collected (n = 8)No full text available (n = 0)\nStudies assessed for  outcomes stratified by hepatitis \nB birth dose  (n = 71)    Studies excluded (n = 51)\nOutcome or population not stratified by h epatitis B birth dose (n = 47)\nSystematic reviews/meta -analyses (n = 4)\nStudies extracted for h epatitis B birth dose (n = 20)   \n6\nSummary of publications meeting search criteria\n•Total of 20 studies of hepatitis B \nvaccine administration within 30 days of life included in review \n-Five studies defined birth dose as hepatitis \nB vaccine administered within 24 hours of \nbirth \n•VSD: 1 study\n-Four studies used other terms to define \nhepatitis B vaccine birth dose\n•Terms used:  Given at birth, Birth dose, \nwithin 120 hours of birth \n•One study stated that 85% received hepatitis B on date of birth, none received the vaccine beyond 8 days of life\n•VSD: 1 studyCharacteristic # of Studies\nStudy design RCT 5\nCohort 7\nSurveillance report 2\nCase control 4\nCase series 1\nCross -sectional 1\nVaccine \nadministeredEngerix -B 5\nRecombivax 1\nHepatitis B product not -\nspecified14\nTiming of administration as noted in the paper≤ 24 hours 5\nWithin 8 days of birth 4\nWithin first month of life 11Study characteristics (N = 20)\n7\nStudies evaluating local reactions: Pain \nHepatitis B vaccination within 24 hours of birth (n = 1 study)\nIn one RCT, pain was reported for 7.7% of infants in the 5 days after Engerix -B vaccination. \nStudy Study Type Outcome Outcome Window Comparison groupsLocal reactions\nIntervention Results % \n(N)Comparison Results % \n(N)\nYerushalmi 1997 RCT Pain with movement Within 5 days of vaccination Engerix -B vs BioHepB* 7.7 (4) 2.6 (4)\nYerushalmi 1997 RCT Pain with pressure Within 5 days of vaccination Engerix -B vs BioHepB* 7.7 (4) 1.3 (2)\nStudy Study Type Outcome Outcome Window Comparison groupsLocal reactions\nIntervention Results % \n(N) Comparison Results % \n(N)\nGreenberg 2002 RCT Pain or soreness Within 3 days of vaccinationEngerix -B vs DTaP -HepB, OPV, \nand Hib at 2 months of age8.1 (NR);\n0 (0) severe**35.7 (NR);\n1.6 (NR) severe**,†\nLopez 2002 Cohort Pain or soreness Within 4 days of vaccinationEngerix -B only \n(no comparison group)6.0 (7);\n4.3 (5) severe§NA\nWood 2018 RCT Pain or soreness Within 2 days of vaccinationEngerix -B alone vs Engerix -B+ \ninvestigational acellular Pertussis \nvaccine9.3 (14);\n0 (0) severe¶19.7 (41); \n0.5 (1) severe¶Hepatitis B vaccination within 0-5 days  of birth (n = 3 studies)^\nPain or soreness within the 4 days after Engerix -B was reported for <10% of newborns; few were severe.\nNA = not applicable; NR = not reported\n*The hepatitis B vaccine BioHepB  is not approved for use in the United States\n^Studies indicated hepatitis B administration at birth, within 120 hours of birth**Severe: soreness that caused crying when limb moved; \n†Severe reported for any injection site; §Severe: not defined; ¶Severe: crying when limb moved/spontaneously painful or prevents daily activities8\nStudies evaluating local reactions: Redness or erythema\nHepatitis B vaccination within 0-5 days  of birth (n = 3 studies)^\nRedness or erythema within 4 days after Engerix -B was reported for 8 -20% of newborns; none were severe.\nStudyStudy \nTypeOutcome Outcome Window Comparison groupsLocal reactions\nIntervention Results % (N) Comparison Results % (N)\nGreenberg 2002 RCTRedness or \nerythemaWithin 3 days of vaccinationEngerix -B within 4 days of \nbirth  vs DTaP -HepB, OPV, and \nHib at 2 months of age8.8 (NR);\n0 (0) severe**11.6 (NR); \n0 (0) severe**,†\nLopez 2002 CohortRedness or \nerythema Within 4 days of vaccinationEngerix -B only \n(no comparison group)11.1 (13);\n0 (0) severe**NA\nWood 2018 RCTRedness or \nerythema Within 2 days of vaccinationEngerix -B alone vs Engerix -\nBwith an investigational \nacellular Pertussis vaccine20.0 (30);\n0 (0) severe§27.4 (57);\n0 (0) severe§\nNA = not applicable; NR = not reported\n*The hepatitis B vaccine BioHepB  is not approved for use in the United States \n^Studies indicated hepatitis B administration at birth, within 120 hours of birth\n**Severe: diameter  >20 mm; †Severe reported for any injection site; §Severe: diameter ≥30 mmStudyStudy \nTypeOutcome Outcome Window Comparison groupsLocal reactions\nIntervention Results % (N) Comparison Results % (N)\nYerushalmi 1997 RCTRedness or \nerythemaWithin 5 days of \nvaccinationEngerix -B vs BioHepB* 0 (0) 0 (0)Hepatitis B vaccination within 24 hours of birth (n = 1 study)\nIn one RCT, redness or erythema was not reported in either comparison arm.\n9\nStudies evaluating local reactions: Swelling\nHepatitis B vaccination within 0-5 days  of birth (n = 3 studies)^\nSwelling within 4 days was reported in 0-4% for newborns who received Engerix -B; there were no severe \nreports.\nStudyStudy \nTypeOutcome Outcome Window Comparison groupsLocal reactions\nIntervention Results % (N) Comparison Results % (N)\nGreenberg \n2002RCT Swelling Within 3 days of \nvaccinationEngerix -B vs DTaP -HepB, OPV, and \nHib at 2 months of age0 (0);\n0 (0) severe**16.3 (NR);\n3.1 (NR) severe**,†\nLopez\n2002Cohort SwellingWithin 4 days of \nvaccinationEngerix -B only \n(no comparison group)4.3 (5); \n0 (0) severe**NA\nWood 2018 RCT Swelling Within 2 days of \nvaccinationEngerix -B alone vs Engerix -B+ \ninvestigational acellular Pertussis \nvaccine  4.0 (6);\n0 (0) severe§12.5 (26);\n0 (0) severe§\nNA = not applicable; NR = not reported\n*The hepatitis B vaccine BioHepB  is not approved for use in the United States \n^Studies indicated hepatitis B administration at birth, within 120 hours of birth\n**Severe: diameter  >20 mm; †Severe reported for any injection site; §Severe: diameter ≥30 mmStudyStudy \nTypeOutcome Outcome Window Comparison groupsLocal reactions\nIntervention Results % (N) Comparison Results % (N)\nYerushalmi \n1997RCT SwellingWithin 5 days of \nvaccinationEngerix -B vs BioHepB* 7.7 (4) 2.0 (3)Hepatitis B vaccination within 24 hours of birth (n = 1 study)\nIn one RCT, swelling was reported for 7.7% of newborns in the days after they received Engerix -B.\n10\nStudies evaluating any local reactions\nStudyStudy \nTypeOutcome Outcome Window Comparison groupsLocal reactions\nIntervention Results % \n(N)Comparison Results % (N)\nBassily 1995 RCT Local side effects Within 1 week of vaccinationRecombivax at birth vs \nRecombivax at 18 months 2.8 (5) 1.6 (3)\n11Hepatitis B vaccination within 0-5 days  of birth (n = 1 study)\nIn one RCT, any local reaction* during the week of Recombivax was reported for 2.8% of newborns\n*Local reaction: local soreness, temporary redness/induration at the injection site \nStudies evaluating systemic reactions: Fever\nStudyStudy \nTypeOutcome Outcome Window Comparison groupsSystemic reactionsMeasure of \nAssociation Intervention Results % (N)Comparison Results \n% (N)\nBassily  1995 RCT FeverWithin 1 week of \nvaccinationRecombivax at birth vs \nRecombivax at 18 months5.6 (10) 2.1 (4) NR\nLinder 1999 Cohort Fever, >37.5 °CWithin birth \nhospitalizationHepatitis B vaccine vs No \nHepatitis B vaccine 1.2 (68) 0.5 (27) p = 0.001\n0.9 (50) >38° C 0.5 (27) >38° C p = 0.05\nLewis 2001 Cohort FeverWithin first 21 days \nof lifeHepatitis B vaccine  vs. No \nHepatitis B Vaccine0.8 (21) 1.1 (25)aRR§: 0.85 (95%CI: \n0.6-1.1); p=0.28\nYerushalmi \n1997RCT Fever, ≥38 °CWithin 5 days of \nvaccinationEngerix -B vs BioHepB* 0 (0) 1.3 (2) NRHepatitis B vaccination within 24 hours of birth (n = 4 studies)\nFever in the days to weeks after hepatitis B vaccination was reported for 0 -5.6% of newborns\nStudyStudy \nTypeOutcome Outcome Window Comparison groupsSystemic reactionsMeasure of \nAssociation\nIntervention Results % \n(N)Comparison Results % \n(N)\nGreenberg \n2002RCT Fever, ≥38.0oCWithin 3 days of \nvaccinationEngerix -B vs DTaP -HepB, \nOPV, and Hib at 2 months \nofage5.9 (NR);\n0 (NR) >39.5oC14.7 (NR); \n0.8 (NR) >39.5oCNR\nWood 2018 RCT Fever, ≥38.0oCWithin 2 days of \nvaccinationEngerix -B alone vs Engerix -B+ \ninvestigational \nacellular Pertussis vaccine0.7 (1);\n0 (0) ≥39.0oC0 (0);\n0 (0) ≥39.0oCNR\nLopez 2002 Cohort Fever, ≥38.0oCWithin 4 days of \nvaccinationEngerix -B only\n(no comparison group)0.9 (1);\n0.9 (1) >39.0oC axillary \nor >39.5° C rectalNA NAHepatitis B vaccination within 0-5 days  of birth (n  =  3 studies)^\nFever within 4 days after Engerix -B vaccination was reported for 0 -5.9% of newborns; few were severe. \nNA = not applicable; NR = not reported. * The hepatitis B vaccine BioHepB  is not approved for use in the United States.; ^Studies indicated hepatitis B administration at birth, within 120 hours of birth \n§ Adjusted relative risk; Adjusted for maternal age, low Apgar at 1 minute, low Apgar at 5 minutes, maternal smoking, gestation  period and congenital heart disease status 12\nStudies evaluating systemic reactions: anorexia or decreased appetite\nStudyStudy \nTypeOutcome Outcome Window Comparison groupsSystemic reactions\nIntervention Results % (N) Comparison Results % (N)\nGreenberg 2002 RCTAnorexia/Decreased \nappetite Within 3 days of \nvaccinationEngerix -B vs DTaP -HepB, OPV, and \nHib at 2 months of age14.0 (NR);\n1.5 (NR) severe**25.6 (NR);\n0.8 (NR) severe**\nLopez 2002 CohortAnorexia/Decreased \nappetite Within 4 days of \nvaccinationEngerix -B only \n(no comparison group)2.6 (3);\n1.7 (2) severe†NA\nWood 2018 RCTFeeding \nissues/Decreased \nappetite Within 2 days of \nvaccinationEngerix -B alone vs Engerix -B+ \ninvestigational acellular Pertussis \nvaccine16.5 (17);\n1.0 (1) severe§12.7 (28);\n0 (0) severe§\n**Severe: prevents normal daily activities; †Severe: not defined; §Severe: prevents normal daily activities or requires significant medical interventionHepatitis B vaccination within 0-5 days  of birth ( n= 3 studies)^\nAnorexia or decreased appetite was reported for 2.6 -16.5% of newborns after Engerix -B vaccination; there \nwere few severe reports.StudyStudy \nTypeOutcome Outcome Window Comparison groupsSystemic reactions\nIntervention Results % \n(N)Comparison Results % \n(N)\nYerushalmi 1997 RCT Anorexia/ decreased appetite Within 5 days of vaccination Engerix -B vs BioHepB* 0 (0) 2.0 (3)\nNA = not applicable; NR = not reported\n*The hepatitis B vaccine BioHepB  is not approved for use in the United States \n^Studies indicated hepatitis B administration at birth, within 120 hours of birthHepatitis B vaccination within 24 hours of birth (n = 1 study)\nIn one RCT, anorexia or decreased appetite was not reported for newborns who received Engerix -B. \n13\nStudies evaluating systemics reactions:  Gastrointestinal (GI) symptoms \nStudyStudy \nTypeOutcome Outcome Window Comparison groupsSystemic reactions\nIntervention Results % (N)Comparison \nResults % (N)\nGreenberg 2002 RCT DiarrheaWithin 3 days \nofvaccinationEngerix -B vs DTaP -HepB, OPV, and Hib \nat 2 months ofage8.1 (NR);\n0.7 (NR) severe**10.1 (NR);\n0 (0) severe**\nWood 2018 RCT DiarrheaWithin 2 days \nofvaccinationEngerix -Balone vs Engerix -B+ \ninvestigational acellular Pertussis \nvaccine11.7 (12);\n0 (0) severe†17.2 (38);\n0 (0) severe†\nGreenberg 2002 RCT VomitingWithin 3 days of \nvaccinationEngerix -B vs DTaP -HepB, OPV, and Hib \nat 2 months ofage4.4 (NR);\n0 (0) severe**7.8 (NR); \n0 (0) severe**\nWood 2018 RCT VomitingWithin 2 days of \nvaccinationEngerix -Balone vs Engerix -B+ \ninvestigational acellular Pertussis \nvaccine22.3 (23);\n0 (0) severe†20.4 (45);\n0 (0) severe†\nNR = not reported\n*The hepatitis B vaccine BioHepB  is not approved for use in the United States \n^Studies indicated hepatitis B administration at birth, within 120 hours of birth**Severe: prevents normal daily activities; \n†Severe: prevents normal daily activities or requires significant medical interventionHepatitis B vaccination within 0-5 days  of birth (n = 2 studies)^\nGI symptoms were reported for 0 -22% of newborns who received Engerix -B; there were no reports.StudyStudy \nTypeOutcome Outcome Window Comparison groupsSystemic reactions\nIntervention Results % \n(N)Comparison Results % \n(N)\nYerushalmi 1997 RCT Diarrhea or vomitingWithin 5 days of \nvaccinationEngerix -B vs BioHepB* 0 (0) 0.6 (1)Hepatitis B vaccination within 24 hours of birth (n = 1 study)\nIn one RCT, diarrhea or vomiting was not reported for newborns who received Engerix -B\n14\nHepatitis B vaccination within 24 hours of birth (n = 1 study)\nIn one RCT, irritability or fussiness was reported for 11.5% of infants in the days after Engerix -B vaccination.\nStudyStudy \nTypeOutcome Outcome Window Comparison groupsSystemic reactions\nIntervention Results % \n(N)Comparison Results % \n(N)\nGreenberg 2002 RCT Irritability or fussinessWithin 3 days of \nvaccinationEngerix -B vs DTaP -HepB, OPV, and Hib \nat 2 months of age22.1 (NR)\n0.7 (NR) severe**54.3 (NR);\n3.9 (NR) severe**\nWood 2018 RCT Irritability or fussinessWithin 2 days of \nvaccinationEngerix -B alone vs Engerix -B+ \ninvestigational acellular Pertussis \nvaccine20.4 (21);\n1.0 (1) severe†24.4 (54);\n0.9 (2) severe†\nLopez 2002 Cohort Irritability or fussinessWithin 4 days of \nvaccinationEngerix -B only \n(no comparison group)2.6 (3);\n1.7 (2) severe§NA\nGreenberg 2002 RCT Unusual cryingWithin 3 days of \nvaccinationEngerix -B vs DTaP -HepB, OPV, and Hib \nat 2 months ofage1.5 (NR);\n0 (0) severe**3.1 (NR);\n0.8 (NR) severe**\nNA = not applicable; NR = not reported\n*The hepatitis B vaccine BioHepB  is not approved for use in the United States \n^Studies indicated hepatitis B administration at birth, within 120 hours of birth\n**Severe: prevents normal daily activities; †Severe: prevents normal daily activities or requires significant medical intervention ; §Severe: not definedHepatitis B vaccination within 0-5 days  of birth (n = 3 studies)^\nIrritability, fussiness, or crying was reported for 1.5 -22.1% of newborns who received Engerix -B; there were \nfew severe reports.StudyStudy \nTypeOutcome Outcome Window Comparison groupsSystemic reactions\nIntervention Results % \n(N)Comparison Results % \n(N)\nYerushalmi 1997 RCT Irritability or fussinessWithin 5 days of \nvaccinationEngerix -B vs BioHepB* 11.5 (6) 3.3 (5)\n15Studies evaluating systemic reactions:  Irritability or fussiness or crying\nStudies evaluating systemic reactions: Sleep disturbance\nStudyStudy \nTypeOutcomeOutcome \nWindowComparison groupsSystemic reactions\nIntervention Results % (N) Comparison Results % (N)\nGreenberg \n2002RCTDrowsiness or \nsleeping moreWithin 3 days \nof vaccinationEngerix -Bvs DTaP -HepB, OPV, and Hib at 2 \nmonths of age 32.4 (NR);\n2.9 (NR) severe*40.3 (NR); \n0.8 (NR) severe*\nWood \n2018RCTDrowsiness or \nsleeping moreWithin 2 days \nof vaccinationEngerix -B alone vs Engerix -B+ \ninvestigational acellular Pertussis vaccine 27.2 (28);\n1.0 (1) severe§17.6 (39);\n0.5 (1) severe§\nLopez \n2002CohortDrowsiness or \nsleeping moreWithin 4 days \nof vaccinationEngerix -B only \n(no comparison group)5.1 (6);\n0.9 (1) severe†NA\nGreenberg RCTRestlessness or \nsleeping lessWithin 3 days \nof vaccinationEngerix -B vs DTaP -HepB, OPV, and Hib at 2 \nmonths ofage16.9 (NR);\n1.5 (NR) severe*26.4 (NR);\n0.8 (NR) severe*\nWood \n2018RCTRestlessness or \nsleeping lessWithin 2 days \nof vaccinationEngerix -B alone vs Engerix -\nB+investigational acellular Pertussis vaccine31.1 (32);\n2.9 (3) severe§22.2 (49);\n0.9 (2) severe§\nNA = not applicable; NR = not reported\n^Studies indicated hepatitis B administration at birth, within 120 hours of birth\n*Severe: prevents normal daily activities; †Severe: not defined; §Severe: prevents normal daily activities or requires significant medical interventionThere were no studies evaluating sleep disturbance for children who received hepatitis B vaccine within \n24 hours of birth \nHepatitis B vaccination within 0-5 days  of birth (n = 3 studies)^\nSleep disturbances were reported for 5.1 -32.4% of newborns who received Engerix -B; there were few severe \nreports .\n16\nStudies evaluating allergic reaction or atopy\nStudyStudy \nTypeOutcome Outcome Window Comparison groupsAllergic Reaction\nMeasure of \nAssociation Intervention \nResults % (N)Comparison \nResults % (N)\nLewis 2001 Cohort Allergic reaction Within 3 weeks of life Hepatitis B vaccine vs No hepatitis B vaccine <0.1 (1) <0.1 (1)RR†: 0.87 \n(95% CI: 0.05- 13.8); \np=0.99Hepatitis B vaccination within 24 hours of birth (n = 1)\nThere were no differences between vaccinated and unvaccinated newborns in the proportion of those \nwho received care for an allergic reaction in the first 21 days of life.\n†Relative risk 17There were no studies evaluating allergic reaction or atopy for newborns who received hepatitis B vaccine within \n0-5 days  of birth \nStudies evaluating infections\nStudyStudy \nTypeOutcome Outcome Window Comparison groupsNumber of cultures\nMeasure of \nAssociation Intervention \nResults % (N)Comparison Results % \n(N)\nLewis 2001 CohortBlood or CSF culture \nperformedWithin 3 weeks of lifeHepatitis B vaccine vs no \nhepatitis B vaccine4.6 (126) 8.6 (203)RR: 0.71 (95% CI: 0.63-\n0.80); p<0.001\nLewis 2001 CohortBlood or CSF culture \npositiveWithin 3 weeks of lifeHepatitis B vaccine vs no \nhepatitis B vaccine 0.3 (7) 0.7 (16)RR: 0.57 (95% CI: 0.35-\n0.94); p=0.027Hepatitis B vaccination within 24 hours of birth (n = 1 )\nNewborns vaccinated against hepatitis B were less likely to be evaluated for possible sepsis and less \nlikely to have a positive blood or cerebrospinal fluid (CSF) culture.\n†Relative risk 18There were no studies evaluating infection for newborns who received hepatitis B vaccine within 0-5 \ndays  of birth \nStudies evaluating other adverse events\nStudyStudy \nTypeOutcome Outcome Window Comparison groupsAdverse Event\nMeasure of \nAssociation Intervention \nResults % (N)Comparison Results % \n(N)\nLewis 2001 Cohort Seizures Within 3 weeks of lifeHepatitis B vaccine vs no \nhepatitis B vaccine0.04 (1) 0.17 (4)RR†: 0.22 (95% CI: \n0.02- 1.9), p=0.19\nLewis 2001 CohortNeurological \ndisorders other than \nseizuresWithin 3 weeks of lifeHepatitis B vaccine vs no \nhepatitis B vaccine0.15 (4) 0.08 (2)RR†: 1.7 (95% CI: 0.3-\n9.4), p=0.69\nMorgan \n2025*CohortBPD in preterm \ninfants born at <29 \ngestational weeks36 weeks postmenstrual \nage**Hepatitis B vaccine vs no \nHepatitis B vaccine50.7 (155) 61.9 (317)aRR§: 0.83 (95% CI: \n0.68- 1.0)Hepatitis B vaccination within 24 hours of birth (n = 3)\nHepatitis B vaccination does not appear to affect risk of seizures or neurological disorders. It may have a \nslight protective effect on bronchopulmonary dysplasia (BPD) among preterm infants.\nStudyStudy \nTypeOutcome Outcome Window Comparison groupsAdverse Event\nMeasure of \nAssociation Intervention \nResults % (N)Comparison Results % \n(N)\nLopez 2002 Cohort Serious adverse eventWithin 30 days of \nvaccinationEngerix -B only \n(no comparison)0.9 (1) NA NAHepatitis B vaccination within 0-5 days  of birth (n =1)\nThere was one report of cough requiring hospitalization 37 days after Engerix -B birth dose vaccination.\n19NA = not applicable; *Extremely preterm infants <29 weeks gestation; †Relative risk\n§ Adjusted relative risk; Adjusted for maternal age, low Apgar at 1 minute, low Apgar at 5 minutes, maternal smoking, gestation  period and congenital heart disease status (unadjusted RR: 0.81; 95% CI: \n0.67- 0.98); ** A diagnosis of BPD was evaluated for all infants once they reached 36 weeks postmenstrual age\nStudies evaluating all cause mortality\nStudy Study Type OutcomeOutcome \nWindowComparison groupsDeathsMeasure of \nAssociationIntervention \nResults % (N)Comparison Results \n% (N)\nMorgan \n2025*CohortAll-cause mortality in \npreterm infants born at \n<29 gestational weeksWithin 3 \nmonths of lifeHepatitis B Vaccine vs No Hepatitis \nBVaccine2.3 (7) † 2.7 (14)aRR§: 1.13 \n(95%CI: 0.42-\n2.81)Hepatitis B vaccination within 24 hours of birth (n = 1 )\nThere were no differences in all cause-mortality within 3 months of life among preterm infants who \nreceived hepatitis B vaccine within 24 hours of birth and those who did not.\nStudyStudy \nTypeOutcomeOutcome \nWindowComparison groupsNeonatal deathsMeasure of \nAssociationIntervention Results \n% (N)Comparison Results \n% (N)\nEriksen 2004 CohortExpected neonatal \ndeathWithin 29 days of \nvaccinationHepatitis B Vaccine vs No Hepatitis \nBVaccine69 (50) 65 (128) p=0.6\nEriksen 2004 CohortUnexpected neonatal \ndeathWithin 29 days of \nvaccinationHepatitis B Vaccine vs No Hepatitis \nBVaccine31 (22) 35 (68) p=0.6\nEriksen 2004 CohortUnexpected neonatal \ndeath from SIDSWithin 29 days of \nvaccinationHepatitis B Vaccine vs No Hepatitis \nBVaccine3.3 per 100,000 \nbirths3.3 per 100,000 \nbirthsp=0.99\nGreenberg  2\n002RCT All-cause mortalityWithin 7 months \nofvaccinationEngerix -B vs DTaP -HepB , OPV, and Hib 0 (0) 0 (0) NAHepatitis B vaccination within 0-8 days  of birth (n = 2 studies)^\nOne cohort suggested no difference in expected or unexpected deaths, deaths due to SIDS, among newborns who received hepatitis B vaccine and those who did not. There were no deaths reported in one RCT. \nNA = not applicable.\n^ Greenberg indicated hepatitis B administration occurred within 4 days (median 1 day) of birth. Eriksen stated that 85% receive d HBV on date of birth, none received the vaccine beyond 8 days of life\n*Extremely preterm infants <29 weeks gestation. † Infants may have received other vaccines within the 3 -month period. The cause of death for most of these infants appeared to be unrelated to the disease \nand multifactorial in nature, with most deaths probably a result of prematurity or congenital abnormalities (i.e. preceding t he HBV vaccination). § Adjusted relative risk; Adjusted for maternal age, low Apgar \nat 1 minute, low Apgar at 5 minutes, maternal smoking, gestation period and congenital heart disease status (unadjusted RR: 0 .83; 95% CI: 0.32– 2.00)20\nLack of association between hepatitis B birth immunization and \nneonatal death: A population- based study from the Vaccine Safety \nDatalink Project\n•Methods:\n•Birth cohort was defined from Southern and Northern California Kaiser Permanente Health Plans of more than \n350,000 live births from 1993 –  1998\n•All deaths were ascertained occurring under 29 days of age\n•Expected deaths: \n•Deaths among extremely low birth weight (ELBW) neonates (defined as birth weight 600 g or extremely preterm 24 \nweeks of gestation)\n•Death because of lethal congenital anomalies or other genetic conditions \n•Deaths from multiple cardiac or multiple (individually) nonlethal conditions\n•Potentially fatal conditions present at or within several hours of birth, such as neonatal sepsis or severe respiratory distress syndrome\n.\n•Unexpected deaths: No apparent preexisting medical conditions\n•The proportion of deaths among birth hepatitis b vaccinated and unvaccinated were compared\n•Medical record review conducted\n•Results:\n•1,363 neonatal deaths identified during the study period\n•66% of the entire birth cohort received hepatitis B vaccine at birth\n•Among all deaths, only 5% (72) neonates who died received hepatitis vaccine at birth \n•No significant difference in the proportion of hepatitis B vaccinated to unvaccinated dying of unexpected causes\n•Conclusion: A relationship between hepatitis B and neonatal death was not identified\nEriksen EM, Perlman JA, Miller A, et al. Lack of association between hepatitis B birth immunization and neonatal death: A pop ulation -based study from the Vaccine Safety Datalink Project. Pediatr  Infect Dis J . \nJuly 2004;23(7):656- 661. doi:10.1097/01.inf.0000130953.08946.d0\nLimitation of rapid systematic review\n22•Not all papers specified the exact timing of hepatitis B administration\n•There were variable approaches to data collection, data analysis, and \nreporting in the studies\n•Primary end points included short -term outcomes (e.g., <30 days) such as \nreactogenicity and mortality \n•Studies that met the inclusion criteria of hepatitis B administration within 24 hours or at birth did not include long -term outcomes\n•Studies that did not meet the inclusion criteria of hepatitis b administration within 24 \nhours or at birth do include long -term safety outcomes (e.g., > 30 days)\nSummary of evidence\n•The safety data available for hepatitis B vaccine administered at birth did not \nidentify an increased risk: \n-Allergic reaction\n-All-cause mortality \n-Expected, or unexpected deaths or deaths due to sudden infant death syndrome (SIDS) \n-Seizures or neurologic disease other than seizures\n•Compared to those who did not receive a hepatitis B vaccine administered at birth, there was a reduction in risk among those who received hepatitis B vaccine for:\n-An invasive diagnostic procedure (blood and CSF cultures) and a reduction in positive \ncultures \n-Bronchopulmonary dysplasia\n•Reactogenicity within 1 week of vaccination varied by study. \n23\nReferences (1 of 2)\n24Studies that defined birth dose as hepatitis B vaccine administered within 24 hours of birth \n• Bassily  S, Kotkat A, Gray G, et al. Comparative study of the immunogenicity and safety of two dosing schedules of hepatitis B vaccine in neonat es. Am J Trop Med Hyg . Oct \n1995;53(4):419- 22. doi:10.4269/ajtmh.1995.53.419\n• Lewis E, Shinefield  HR, Woodruff BA, et al. Safety of neonatal hepatitis B vaccine administration. Pediatr Infect Dis J . Nov 2001;20(11):1049- 54. doi:10.1097/00006454-\n200111000- 00009\n• Linder N, Raz M, Reichman B, et al. Unexplained fever in neonates may be associated with hepatitis B vaccine. Archives of Disease in Childhood: Fetal and Neonatal Edition . \n1999;81(3):F206- F207. doi:10.1136/fn.81.3.F206\n• Morgan HJ, Nold MF, Kattan GS, et al. Hepatitis B vaccination of preterm infants and risk of bronchopulmonary dysplasia: a co hort study, Australia. Vaccination contre  l'hepatite  \nB de prematures  et risque  de dysplasie  bronchopulmonaire : etude de cohorte  en Australie , Vacunacion  contra la hepatitis B en neonatos  prematuros  y riesgo  de displasia \nbroncopulmonar : estudio  de cohortes  en Australia. Bull World Health Organ . 2025;103(3):187- 193. doi:10.2471/BLT.24.291683\n• Yerushalmi B, Raz R, Blondheim O, Shumov  E, Koren R, Dagan R. Safety and immunogenicity of a novel mammalian cell -derived recombinant hepatitis B vaccine containing Pre-\nS1 and Pre -S2 antigens in neonates. Pediatr  Infect Dis J . Jun 1997;16(6):587- 92. doi:10.1097/00006454- 199706000- 00009\nStudies that indicated hepatitis B vaccine administered within 0 -8 days of birth\n• Eriksen EM, Perlman JA, Miller A, et al. Lack of association between hepatitis B birth immunization and neonatal death: A popula tion -based study from the Vaccine Safety \nDatalink Project. Pediatr  Infect Dis J . July 2004;23(7):656- 661. doi:10.1097/01.inf.0000130953.08946.d0\n• Greenberg DP, Wong VK, Partridge S, Howe BJ, Ward JI. Safety and immunogenicity of a combination diphtheria -tetanus toxoids -acel lular pertussis -hepatitis B vaccine \nadministered at two, four and six months of age compared with monovalent hepatitis B vaccine administered at birth, one month  and six months of age. Pediatr  Infect Dis J . Aug \n2002;21(8):769- 77. doi:10.1097/00006454- 200208000- 00014\n• Lopez P, Rubiano L, del Pilar Rubio M, David MP, Safary A. Immunogenicity and reactogenicity of DTPw -HB/Hib vaccine administered to colombian  infants after a birth dose of \nhepatitis B vaccine. Clinical Trial. Expert Rev Vaccines. Oct 2002;1(3):277- 83. doi:10.1586/14760584.1.3.277\n• Wood N, Nolan T, Marshall H, et al. Immunogenicity and Safety of Monovalent Acellular Pertussis Vaccine at Birth: A Randomize d Clinical Trial. Jama, Pediatr . 11 01 \n2018;172(11):1045- 1052. doi:10.1001/jamapediatrics.2018.2349\nReferences (2 of 2)\n25Studies that indicated hepatitis B vaccine administered within >8 days of birth and within first month of life\n•Gallagher CM, Goodman MS. Hepatitis B vaccination of male neonates and autism diagnosis, NHIS 1997 -2002. Journal of Toxicology and Environmental Health -  Part A: Current Issues . \nJanuary 2010;73(24):1665- 1677. doi:10.1080/15287394.2010.519317\n•Geier DA, Hooker BS, Kern JK, King PG, Sykes LK, Geier MR. A two -phase study evaluating the relationship between Thimerosal -cont aining vaccine administration and the risk for an autism \nspectrum disorder diagnosis in the United States. Transl  Neurodegener . Dec 19 2013;2(1):25. doi:10.1186/2047 -9158- 2-25\n•Geier DA, Kern JK, Hooker BS, et al. Thimerosal exposure and increased risk for diagnosed tic disorder in the United States: A case-control study. Interdisciplinary Toxicology . 01 Jun \n2015;8(2):68- 76. doi:10.1515/intox -2015- 0011\n•Geier DA, Kern JK, Hooker BS, King PG, Sykes LK, Geier MR. A longitudinal cohort study of the relationship between Thimerosal -containing hepatitis B vaccination and specific delays \nindevelopment in the United States: Assessment of attributable risk and lifetime care costs. Journal of Epidemiology and Global Health. 01 Jun 2016;6(2):105-\n118. doi:10.1016/j.jegh.2015.06.002\n•Geier DA, Kern JK, Homme KG, Geier MR. Thimerosal exposure and disturbance of emotions specific to childhood and adolescence:  A case -control study in the Vaccine Safety Datalink \n(VSD) database. Brain Injury. 28 Jan 2017;31(2):272- 278. doi:10.1080/02699052.2016.1250950\n•Geier DA, Kern JK, Geier MR. Premature puberty and thimerosal -containing Hepatitis B vaccination: A case -control study in the va ccine safety datalink. Toxics. 15 Nov 2018;6(4) (no \npagination)67. doi:10.3390/toxics6040067\n•Haber P, Moro PL, Ng C, et al. Safety of currently licensed hepatitis B surface antigen vaccines in the United States, Vaccin e Adverse Event Reporting System (VAERS), 2005 -2015. Historical \nArticle. Vaccine. 01 25 2018;36(4):559- 564. doi:10.1016/j.vaccine.2017.11.079\n•Niu MT, Davis DM, Ellenberg S. Recombinant hepatitis B vaccination of neonates and infants: emerging safety data from the Vac cine Adverse Event Reporting System. Pediatr Infect Dis J. \nSep 1996;15(9):771- 6. doi:10.1097/00006454- 199609000- 00007\n•Niu MT, Salive  ME, Ellenberg SS. Neonatal deaths after hepatitis B vaccine: the vaccine adverse event reporting system, 1991 -1998. Arch Pediatr  Adolesc  Med . Dec 1999;153(12):1279- 82. \ndoi:10.1001/archpedi.153.12.1279\n•Sapru A, Kulkarni PS, Bhave S, Bavdekar A, Naik SS, Pandit AN. Immunogenicity and reactogenicity of two recombinant hepatitis B vaccines in small infants: a randomiz ed, double -blind \ncomparative study. J Trop Pediatr. Oct 2007;53(5):303- 7. doi:10.1093/ tropej /fmm016\n•Verstraeten  T, Davis RL, DeStefano F, et al. Safety of Thimerosal- Containing Vaccines: A Two -Phased Study of Computerized Health Maintenanc e Organization Databases. Pediatrics. \nNovember 2003;112(5):1039- 1048. doi:10.1542/peds.112.5.1039\nFor more information, contact CDC\n1-800- CDC- INFO (232- 4636)\nTTY:  1 -888- 232- 6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.\nQuestions?", "summary": "A Review of the Safety of Hepatitis B Birth Dose  Vaccination John Su Acting Director Immunization Safety Office Centers for Disease Control and Prevention September 18, 2025National Center for Emerging and Zoonotic Infectious Diseases Request to CDC from ACIP Chair Safety data for HepB administration within 24 hours of birth from CDC’s  Vaccine Safety Datalink and from FDA’s Biologics Effectiveness and Safety  System. Include (i) mild and serious adverse events; (ii) all cause morbidity and…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-september-18-19-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-09-18-19/02-su-hep-b-508.pdf", "doc_date": "2025-09-18", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 26}
{"title": "03 su hep b 508", "content": "Non -specific effects following hepatitis B \nvaccinationNational Center for Emerging and Zoonotic Infectious Diseases\nJohn Su\nActing DirectorImmunization Safety OfficeCenters for Disease Control and Prevention\nSeptember 18, 2025\n1\nRequest to CDC from ACIP chair\nPresent the results for the HepB  vaccine from the study by Garly ML, \nJensen H, Martins CL, Balé  C, Baldé MA, Lisse IM, Aaby P . Hepatitis B \nvaccination associated with higher female than male mortality in Guinea -\nBissau: an observational study. The Pediatric infectious disease journal. \n2004 Dec 1;23(12):1086 -92.\n2\nOutline\n•Review non -specific effects following vaccination\n•Summarize Garly, et al. 2004 paper\n•Through a rapid systematic review of non- specific effects following hepatitis \nB vaccination, provide available evidence related to mortality following \nhepatitis B vaccination\n3\nNon-specific effects following vaccination\nPittet L, Netea MG, Curtis N. Chapter 3 -  Non-specific Effects of Vaccines. In: Stanley A. Plotkin WAO, Paul A. Offit, and Kathryn M. Edwards, ed.Plotkin's Vaccines. 8 ed. Elsevier; 2023:37 -44.e7:chap 3.•In addition to protecting against their target disease, vaccines may \ninduce changes in the immune system that have broader effects\n•Non -specific effects (NSE) are distinct from adverse events, cross -\nprotective, and downstream indirect effects\n•Clinical manifestations of NSE\n-All-cause mortality\n-Unrelated infections\n-Risk of allergic and autoimmune disease\n•Live -attenuated and non-live vaccines may have differential NSE\n4\nSummary of Garly, et al. 2004 article\n5\nBackground\n•Several studies have examined the non- specific effects of \nvaccines on all -cause mortality\n•Few studies had examined a potential impact of hepatitis B \nvaccination and mortality\n•Objective of Garly, et al. 2004 paper:\n-Is hepatitis B vaccine associated with sex -specific differences in \nmortality?\n6\nMethods\n•Study setting:\n-Guinea -Bissau Bandim Health Project surveillance system \n-Enrolled  inmeasles vaccine trial1\n•Study population: \n-Birth cohorts, March 1994 – February 2000\n-Children born March 1996 –February 1997, eligible for hepatitis B vaccine\n•Study design: prospective cohort\n•Exposure:  \n-3 doses of hepatitis B vaccine given at 7.5, 9, and 10.5 months of age\n-Human plasma- derived hepatitis B vaccine, Hepaccine  (not a U.S. licensed vaccine)2\n1. Garly ML, Martins CL, Balé  C, da Costa F, Dias F, Whittle H, Aaby P. Early two -dose measles vaccination schedule in Guinea -Bissau: good protection and cov erage in infancy. Int J \nEpidemiol. 1999 Apr;28(2):347 -52. doi: 10.1093/ ije/28.2.347. PMID: 10342702.\n2. Heppacine  is not approved for use in the United States; HEPACCINE -B INJECTION - 27/30.1/0128; HEPACCINE -B MULTIDOSE INJECTION - 27/30.1/0129; HEPACCINE -B PAEDIATRIC \nINJECTION - 27/30.1/0127; HEPACCINE -B PAEDIATRIC 2 DOSE INJECTION -  27/30.1/0422; HEPACCINE -B PAEDIATRIC MULTIDOSE INJECTION - 27/30.1/0423 7\nMethods\n•Three mortality comparisons:\n1.Children aged 7.5 - 12 vs 1.5 - 7.5 months, all birth cohorts\n2.Hepatitis B -vaccinated vs hepatitis B -unvaccinated (subset in 2-dose \nmeasles vaccine (MV) trial)\n3.Female -to-male , hepatitis B -vaccinated vs hepatitis B -unvaccinated \n(among those who received MV; HBV+MV vs MV alone)\n8\nResults\n•Comparison 1 (N = 8,906)\n-Mortality  rate ratio (MRR) was 0.97 (95% CI, 0.77- 1.23) for the HBV -unvaccinated cohorts comparing \n7.5- 12-month  to 1.5- 7.5 month age groups\n-Among the birth cohorts when most children received HBV (7.5 months of age ),children had \nincreased mortality [MRR 1.62 (95% CI 1.09, 2.41)] comparing 7.5- 12-month to 1.5- 7.5 month age \ngroups\n•Comparison 2 (N= 5,441)\n-Among children enrolled in the MV trial, compared with HBV -unvaccinated children, the MRR for \nchildren 7.5- 12 months of age from the HBV -vaccinated cohort was 1.81 (95% CI 1.19, 2.75)\n•Comparison 3 (N=5,061)\n-The female -to-male  MRR was 1.66 (95% CI 0.80- 3.45) in the cohort  who received both HBV and MV \nthrough 12 months of age\n-The female -to-male MRR was 2.20 (95% CI 1.07, 4.54) in cohort who received both HBV and MV and \n0.96 (95% CI 0.70, 1.32) in the MV only cohort through 24 months of age\n9\nConclusions\n•Garly, et al. concludes, using 3 different tests of the same intervention:\n-Changes in the mortality pattern after the introduction of hepatitis B vaccine in a \nhigh mortality setting\n-Higher mortality between 7.5 and 12 months of age among children who \nreceived hepatitis B vaccine compared to those who did not, within a 2 -dose \nmeasles vaccine trial\n-The effect was found to be stronger for females than for males\n-Hepatitis B vaccine may have sex -differential non -specific effects\n10\nLimitations and Implications\n•Analyses were not planned when the trial was designed\n•The study was not randomized, so an unbiased comparison of hepatitis B -\nvaccinated and unvaccinated children from the same period could not \nbemade\n•Effects may differ when hepatitis B vaccine is given at birth and with BCG\n•An increase in the female -to-male mortality ratio could also represent a \nreduction in male mortality\n11\nRapid systematic review of non- specific \neffects of hepatitis B vaccine\n12\nRapid systematic review of non- specific effects after \nhepatitis B vaccination\n•To inform the Garly et al. 2004 paper, we conducted a rapid systematic \nreview on the non -specific effects (e.g., mortality) after hepatitis B \nvaccination in children\n•The key question used to guide the review: What are the non-\nspecific effects of hepatitis B -containing vaccines administered in \nchildhood?\n13\nRapid systematic review of data on non- specific effects\n•Key question: What are the non -\nspecific effects of hepatitis B -\ncontaining vaccines administered in \nchildhood?\n•Conducted a new rapid systematic \nreview of published literature through August 20, 2025\n•Electronic databases \nsearched: MEDLINE, EMBASE, \nCINAHL, and Cochrane LibraryPI/ECO(ST) \nELEMENTDescription for this Review\nPopulationInfants and children through 6 years of age \nIntervention or \nExposure*Hepatitis B (HBV) – Recombivax HB,Engerix -B\nCombination vaccines – \nPediarix, Kinrix, Quadracel, Vaxelis, Pentacel, ProQuad\nComparator (if applicable)Any or none\nOutcome(s)Non- specific effects\nAll-cause morbidity\nAll-cause mortality (death)\nNon- targeted infection (sepsis, respiratory tract)\nAllergic and atopic disease (asthma, eczema, atopic dermatitis, food allergy)\nAutoimmune and immune- mediated disease (type 1 diabetes mellitus, \ninflammatory bowel disease – ulcerative colitis and Crohn’s disease, \njuvenile idiopathic arthritis, systemic lupus erythematosus, Hashimoto’s \nthyroiditis, alopecia)Malignancy (cancer, leukemia)\nSettingAny\nTime Frame Any publication years\nAny duration of follow up  \n14\nResults\n15\nSystematic review inclusion and exclusion criteria\nInclusion Criteria Exclusion Criteria\n• Clinical trials\n• Observational studies\n• Surveillance reports\n• Systematic reviews• Case reports\n• Case series\n• Narrative reviews\n• Animal studies\n• Infants\n•Children ≤ 6 years of age•Older children ≥7 years of age\n• Adults\n• Hepatitis B vaccines (Hepatitis B, \nH BV, HepB, Engerix -\nB,Recombivax HB, Pediarix, Vaxelis)• Other vaccines\n• Outcomes include any of the following: non-specific effects, all -cause morbidity, all -\ncause mortality, non- targeted infection, \nallergic and atopic disease, autoimmune and \nimmune -mediated disease, malignancy• Any other outcome\n16\nResults of systematic reviewIdentification Screening IncludedStudies from databases/registers (n = 2068)\nEmbase (n = 1105)\nMEDLINE (n = 811)\nCochrane Library (n = 119)\nCINAHL (n = 33)References removed (n = 0)  \nDuplicates identified manually (n = 0)\nKey word screening for “hepatitis B,” “HBV,” “Hep B,” \n“Engerix -B,” “Recombivax HB,” “ Pediarix ,” “Vaxelis ”(n \n= 2068)Studies excluded (n = 1831)\nStudies sought for retrieval (n = 16)Studies excluded (n = 221)\nStudies assessed for eligibility (n = 16)    Studies excluded (n = 8)  \nWrong study design (case report, case series, etc.) (n=3)\nWrong patient population (children>/=7, adolescents, adults) (n=1)\nWrong intervention (does not evaluate hepatitis B -containing vaccines) (n=4)\nStudies included in review (n = 8) \nStudies screened (n = 237)\nStudies not retrieved (n = 0)\n17\nSummary of publications meeting search criteria\n•Total of 8 studies included in review \n-4 studies evaluated pentavalent, hepatitis B -\ncontaining vaccines* and non -specific effects\n-4 studies evaluated monovalent hepatitis B \nvaccines and non- specific effects\n•Study characteristics (N=8)\n•Presenting results of studies \n(N=4) evaluating monovalent hepatitis B \nvaccination\n*Pentavalent vaccine: Diphtheria- Tetanus -whole cell Pertussis- Hemophilus influenzae type B- Hepatitis BCharacteristic # of Studies\nStudy design Cohort 7\nNested case series 1\nVaccine adm inistered Pentavalent vaccine 4\nM onovalent hepatitis B  vaccine4\nC ountry of study High income country 2\nLo w- and mi ddl e -\nincome country6\nNon-specific effects Mortality 4\nFem ale -to-m ale \nm ortality5\nOther non- specific \neffects1\n18\nStudyStudy \nTypeCountryOutcome and \nWindowComparison armsNon -Specific Effects\nMeasure of \nAssociationIntervention \nResults\n% (n/N or PT)Comparison \nResults\n% (n/N or PT)\nHe 2022 Cohort United StatesAll-cause mortality; \nmedian follow -up of 8 \nyearsHepatitis B vaccine* \nvs no hepatitis B \nvaccine(390/10,785)2.6 \n(4,185/26,006)aHR 0.78 (95%CI: 0.\n68-0.90)\nMorgan \n2025Cohort\n(extrem\nelypret\nerm inf\nants)AustraliaAll-cause mortality; \nwithin 3 months of lifeHepatitis B vaccine vs \nno hepatitis B vaccine2.3 (7/306) 2.7 (14/512)aRR : \n1.13 (95%CI: 0.42-\n2.81)\nGarly 2004 Cohort Guinea -BissauAll-cause mortality; \n7.5 months – \n12months of ageHepatitis B \nvaccine [Hepaccine ] \n+measles vaccine \nvsmeasles vaccineNR/876 NR/4,565MRR \n1.81 (95%CI: 1.19-\n2.75)Studies evaluating mortality\nTwo cohort studies in high- income countries (HIC) showed no association between all -cause \nmortality and hepatitis B vaccination, and one cohort study in a low -and middle -income \ncountry (LMIC) suggested an increase in risk of all -cause mortality after hepatitis B vaccination.\nPT = person -time; aHR = adjust hazard ratio; aRR = adjusted rate ratio; NR = not reported; MRR = mortality rate ratio\n•*Unspecified manufacturer, thimerosal -free 19\nStudyStudy \nTypeCountryOutcome and \nWindowComparison armsNon -Specific Effects\nMeasure of \nAssociationIntervention \nResults\n% (n/N or PT)Comparison \nResults\n% (n/N or PT)\nGarly 2004 Cohort Guinea -BissauFemale -to-\nmale mortality; 7.5 \nmonths – 12months \nof ageHepatitis B vaccine \n[Hepaccine] + \nmeasles vaccine vs \nmeasles vaccine12.5 (18/143.8 \nfemale person-\nyears)7.5 (12159.1 \nmale person-\nyears)MRR 1.66 (95%CI: 0\n.80- 3.45)\nGarly 2004 Cohort Guinea -BissauFemale -to-\nmale mortality; 9 -24 \nmonthsHepatitis B \nvaccine [Hepaccine] \n+ measles vaccine vs \nmeasles vaccine6.1 (22/358 \nfemale person-\nyears)2.8 (11/394.3 \nmale person-\nyears)MRR \n2.20 (95%CI: 1.07-\n4.54)\nAaby 2004Nested \ncase \nseriesThe GambiaFemale -to-\nmale mortality; 18 \nmonths of ageHepatitis B as last \nvaccine vs no \nhepatitis B as last \nvaccine7 (4/60) 0 (0/53) NRStudies evaluating female- to-male mortality\nEvidence is inconsistent about sex -specific mortality after receipt of hepatitis B vaccines in \nLMIC; one study suggests both no difference and an increase in the female -to-male mortality \nratio and one study suggests no difference in mortality by sex.\nPT = person -time; MRR = mortality rate ratio; NR = not reported 20\nStudyStudy \nTypeCountryOutcome \nand WindowComparison armsNon -Specific Effects\nMeasure of \nAssociationIntervention \nResults\n% (n/N or PT)Comparison \nResults\n% (n/N or PT)\nHe 2022 Cohort United StatesCancer- related \nmortality; \nmedian follow -\nup of 8 yearsHepatitis B \nvaccine* vs no \nhepatitis B vaccine0.7 (97/10,785)2.6 \n(881/26,006)aHR 0.76 (95%CI:\n0.58 -1.00)\nHe 2022 Cohort United StatesCardiovascular\n-related \nmortality; \nmedian follow -\nup of 8 yearsHepatitis B vaccine* \nvs no hepatitis B \nvaccine0.4 (53/10,785)1.9 \n(732/26,006)aHR 0.83 (95%CI:\n0.60 -1.15]Studies evaluating other mortality outcomes\nOne cohort study in a HIC suggests no effect of hepatitis B vaccines on \ncancer -related mortality and cardiovascular -related mortality.\nPT = person -time; aHR = adjusted hazard ratio\n*Unspecified manufacturer, thimerosal -free 21\nConclusions\n•Few studies exist to inform the non-specific effects of hepatitis B vaccination\n•Two cohort studies in HIC showed no association between all -cause mortality \nand hepatitis B vaccination\n•One cohort study in an LMIC showed an increase in risk of all -cause mortality \nafter hepatitis B vaccination\n•Evidence is inconsistent about sex -specific mortality after receipt of hepatitis B \nvaccines\n22\nCDC’s interpretation on limitations and implications\n•Non -specific effects (NSE) may vary in settings with different background \nmortality rates and infectious diseases burden\n•NSE may not be generalizable across immunization programs\n-Heppacine  is not licensed for use in the United States\n-In the United States , hepatitis B vaccine is given earlier  and often in combination with \nother routine vaccines\n•Biologic molecular and immunological mechanisms for non-specific effects are \nnot fully understood\n-The interval between vaccination and the onset of NSE, as well as the persistence \nofeffects are uncertain\n-The duration of a vaccine's NSE is complicated by a subsequent vaccination with adifferent vaccine\n23\nReferences\n1.Pittet L, Netea  MG, Curtis N. Chapter 3 -  Non -specific Effects of Vaccines. In: Stanley A. Plotkin WAO, Paul A. Offit, and Kathryn M. Edwards, \ned. Plotkin's Vaccines . 8 ed. Elsevier; 2023:37- 44.e7:chap 3.\n2.Aaby P, Jensen H, Walraven G. Age -specific changes in the female -male mortality ratio related to the pattern of vaccinations: An observational \nstudy from rural Gambia. Vaccine . 29 May 2006;24(22):4701 -4708. doi:10.1016/j.vaccine.2006.03.038\n3.Aamand T, Fisker AB, Correia C, Fernandes M, Clipet -Jensen C, Thysen  SM. Do Pentavalent ( DTwP -Hib-HBV) vaccines have sex -differential \nnonspecific effects? An observational study. Observational Study Research Support, Non -U.S. Gov't. Hum Vaccin  Immunother . 12 15 \n2023;19(3):2288297. doi:10.1080/21645515.2023.2288297\n4.Fisker AB, Biering -Sorensen S, Lund N, et al. Contrasting female -male mortality ratios after routine vaccinations with pentavale nt vaccine versus \nmeasles and yellow fever vaccine. A cohort study from urban Guinea -Bissau. Research Support, Non -U.S. Gov't. Vaccine . 08 31 2016;34(38):4551 -\n4557. doi:10.1016/j.vaccine.2016.07.034\n5.Fisker AB, Thysen  SM. Non -live pentavalent vaccines after live measles vaccine may increase mortality. Research Support, Non- U.S. Gov't. Vaccine . \n10 01 2018;36(41):6039 -6042. doi:10.1016/j.vaccine.2018.08.083\n6.Garly ML, Jensen H, Martins CL, et al. Hepatitis B vaccination associated with higher female than male mortality in Guinea- Bissa u: An observational \nstudy. Pediatr  Infect Dis J . December 2004;23(12):1086 -1092. doi:10.1097/01.inf.0000145700.77286.94\n7.Hanifi SMA, Biering -Sorensen S, Jensen AKG, Aaby P, Bhuiya A. Penta is associated with an increased female -male mortality ratio:  cohort study \nfrom Bangladesh. Research Support, Non -U.S. Gov't. Hum Vaccin  Immunother . 01 02 2021;17(1):197 -204. doi:10.1080/21645515.2020.1763084\n8.He WQ, Guo GN, Li C. The impact of hepatitis B vaccination in the United States, 1999 -2018. Hepatology . 06 2022;75(6):1566 -1578. \ndoi:10.1002/hep.32265\n9.Morgan HJ, Nold MF, Kattan GS, et al. Hepatitis B vaccination of preterm infants and risk of bronchopulmonary dysplasia: a co hort study, Australia. \nVaccination contre  l'hepatite  B de prematures  et risque  de dysplasie  bronchopulmonaire : etude de cohorte  en Australie , Vacunacion contra la \nhepatitis B en neonatos prematuros  y riesgo  de displasia broncopulmonar : estudio  de cohortes en Australia. Bull World Health Organ . \n2025;103(3):187 -193. doi:10.2471/BLT.24.291683\n24\nFor more information, contact CDC\n1-800- CDC- INFO (232 -4636)\nTTY:  1 -888- 232- 6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.\nQuestions?", "summary": "Non -specific effects following hepatitis B  vaccinationNational Center for Emerging and Zoonotic Infectious Diseases John Su Acting DirectorImmunization Safety OfficeCenters for Disease Control and Prevention September 18, 2025 1 Request to CDC from ACIP chair Present the results for the HepB  vaccine from the study by Garly ML,  Jensen H, Martins CL, Balé  C, Baldé MA, Lisse IM, Aaby P . Hepatitis B  vaccination associated with higher female than male mortality in Guinea - Bissau: an…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-september-18-19-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-09-18-19/03-su-hep-b-508.pdf", "doc_date": "2025-09-18", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 25}
{"title": "01 levi covid 508", "content": "ACIP Meeting, Atlanta\nSeptember 19, 2025ACIP COVID -19 IMMUNIZATION WG:\nINTRODUCTION\nProfessor Retsef Levi, PhD, MIT\nACIP Meeting, Atlanta\nSeptember 19, 2025Immediate Goals\n1)Formulate possible recommendations regarding the recent FDA authorized \nproducts with respect to sub- populations for discussion and vote during the ACIP \nmeeting on Sep 18- 19 (with supporting data/analyses):\n-What are the appropriate subgroups (age, risk factors, prior infection, others)?\n-Options: Recommend, not recommend, Individual -based decision\n2)Formulate a list of risks and uncertainties the WG suggests should be communicated to patients and medical providers as part of inform consent (changes to the Vaccine Information Statement)\nACIP Meeting, Atlanta\nSeptember 19, 2025Medium -Term Goals\n1)Expansive Terms of Reference\n2)Three focus clusters assigned to WG members based on expertise\n3)The goal for each cluster is to summarize ALL available knowledge for \ndiscussion in the WG and highlight important issues and knowledge gaps\n4)Formulate policy options on broad vaccination- related issues for consideration \nby ACIP\nACIP Meeting, Atlanta\nSeptember 19, 2025Values & Conduct\n1)Leverage all relevant published and unpublished scientific, clinical and public \nhealth data, information and knowledge, including experiences from the field \n2)Personalized risk -benefit analyses vs. ‘safe & effective’ (broad set of questions)\n3)Debate with respect\n4)Communicate the WG members’ diverse positions and opinions with maximum \ntransparency \nACIP Meeting, Atlanta\nSeptember 19, 2025Today’s WG Member Presentations\n1)Professors Wafik El-Deiry (Brown University) and Charlote Kuperwasser (Tuffs \nUniversity):\nSafety Uncertainties of COVID -19 Vaccines \n2)Professor Bruce Carleton (University of British Columbia):Genomics of Vaccine-Induced Myocarditis\n3)Professors Hennery Bernstein (Hofstra/Northwell in New York), Mitchell Miglis (Stanford) \nand Stanely Perlman (University of Iowa)WG Minority Opinion\nACIP Meeting, Atlanta\nSeptember 19, 2025Other ACIP Members on WG\n1.James Pagano, MD, FACEP, Emergency Medicine Physician \nwith More than 40 Years Clinical Experience, ACIP Committee \nMember\n2.Robert Malone, MD, MS, Vaccinologist, Scientist, Biochemist, Contributor to mRNA Vaccine Technology, ACIP Committee \nMember\nACIP Meeting, Atlanta\nSeptember 19, 2025WG External Subject Matter Experts\n1. Henry H. Bernstein, DO, MHCM, FAAP , Professor of \nPediatrics, Zucker School of Medicine at Hofstra/Northwell\n2. Christine Stabell Benn, PhD, DMSc , Bandim Health \nProject, OPEN, Department of Clinical Research, University of Southern Denmark \n3. Bruce Carleton, Pharm.D , Professor, University of \nBritish Columbia\n4. Wafik El-Deiry , MD, PhD, FACP , Director, Legorreta \nCancer Center at Brown University\n5. Joseph Fraiman, MD, Emergency Medicine Physician, Baton Rouge, LA\n6. Suzanne Gazda, MD, Medical Director, Neurology institute of San Antonia (NISA) \n7. Douglas H. Jones, MD, FAAAAI, FACAAI, Board certified American Board of Allergy and Immunology; CEO Global Allergy Immune Network7. Charlotte Kuperwasser, PhD, Professor, \nDevelopmental, Molecular & Chemical Biology, \nDirector, Tufts Convergence Laboratory of Biomedical, Physical, and Engineering Sciences, Tufts University\n8. Mitchell Miglis , MD, Clinical Associate Professor, \nDepartment of Neurology and Neurological Sciences, Secondary in Department of Psychiatry and Behavioral Sciences, Stanford University\n9. Stanley Perlman, MD, PhD, Professor, Department of \nMicrobiology and Immunology, University of Iowa\n10. Erle Robertson, PhD., Harry P . Schenk Endowed Chair \nProfessor, Vice -Chair, Department of \nOtorhinolaryngology, Head and Neck Surgery\n11. Jordan Vaughn, MD, CEO of MedHelp Clinics\nACIP Meeting, Atlanta\nSeptember 19, 2025ACIP Ex Officio\n1.Tracy Beth Hoeg, MD, PHD, Senior Advisor for Clinical \nSciences, Food and Drug Administration Ex Officio\n2.Andrew Johnson, Centers for Medicare & Medicaid Services \nEx Officio", "summary": "ACIP Meeting, Atlanta September 19, 2025ACIP COVID -19 IMMUNIZATION WG: INTRODUCTION Professor Retsef Levi, PhD, MIT ACIP Meeting, Atlanta September 19, 2025Immediate Goals 1)Formulate possible recommendations regarding the recent FDA authorized  products with respect to sub- populations for discussion and vote during the ACIP  meeting on Sep 18- 19 (with supporting data/analyses): -What are the appropriate subgroups (age, risk factors, prior infection, others)? -Options: Recommend, not…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-september-18-19-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-09-18-19/01-levi-covid-508.pdf", "doc_date": "2025-09-18", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 8}
{"title": "02 Srinivasan covid 508", "content": "Updates to COVID -19 epidemiology\nAdvisory Committee on Immunization Practices\nSeptember 19, 2025\n1U.S. Centers for Disease Control and Prevention\n\nCOVID -NET monitors COVID -19 hospitalizations across \nparts of the U.S.\n•RESP -NET includes COVID -NET, RSV -NET, FluSurv -NET\n•Collaboration between state and local health \ndepartments and CDC\n•Includes data from >300 hospitals in 185 counties \nacross 13 states, covering about 10% of the U.S. \npopulation\nCOVID -NET: https://www.cdc.gov/covid/php/covid -net/index.html . 2\nTypes of COVID -NET data\n1.Population -based rates of COVID -19–\nassociated hospitalizations\n-Counts every laboratory -confirmed COVID -\n19–associated hospitalization among \npeople living in COVID -NET counties\n-Includes all hospitalizations that meet the \nCOVID -NET case definition:\n•Laboratory -confirmed SARS -CoV-2-\npositive test result\n•Resident of COVID -NET catchment area\n-Collects some data (age, sex, race/ethnicity, \nsite, test/admission dates) for all cases\n32.Clinical data (including outcomes, \nunderlying medical conditions, \ntreatment, discharge diagnoses)\n-Obtained via detailed medical chart \nreviews from anonymous, random sample \nof hospitalizations (since reviewing every \ncase is not possible)\n•Monthly random sample from each of six \nage groups at each site designed to \nrepresent the broader population\n-Clinical analyses limited to hospitalizations \ndue to COVID -19\nPurpose of COVID -NET data\n1.Population -based rates of\nCOVID -19–associated hospitalizations\n42.Clinical data (including outcomes, \nunderlying medical conditions, \ntreatment, discharge diagnoses)\n•Monitor laboratory -confirmed COVID -19-\nassociated hospitalizations among children \nand adults\n•Provide decision -makers and public with \nbroad and timely (weekly) understanding of \ngeneral trends\n‒Rates published weekly on public \ndashboard since 2020\n•Estimate and compare disease burden over \ntime\n•Respond to rising rates•Categorize hospitalizations that are due to \nCOVID -19\n•Better understand hospitalization trends \nand who is most at risk\n•Track severity of illness\n•Examine how many people hospitalized due \nto COVID -19 have underlying medical \nconditions\n•Provide insight into treatments used\nDefining Hospitalizations in COVID -NET\n5\n1. Definition of COVID -NET hospitalizations for \npopulation -based rates\nHow does COVID -NET define a COVID -19–associated hospitalization?\n•A hospitalization (case) is counted if:\n-The person lives in a defined COVID -NET surveillance catchment area AND\n-Tests positive for SARS -CoV-2 (using a laboratory -based molecular, antigen \nor serology test) within 14 days before or during hospitalization\n6\n1. Definition of COVID -NET hospitalizations for \npopulation -based rates (cont’d)\nWhy use this definition?\n•Designed to monitor overall trends in hospitalizations\n-Simple approach works across hundreds of hospitals\n-Available in near real -time\n-Same definition used to monitor hospitalizations for \nother pathogens (RSV, influenza) in the U.S. and \nworldwide\n•Developed by infectious disease experts\n•Balances accuracy, speed, and broad coverage\n7This approach is used \ninternationally* to conduct \nCOVID -19 hospitalization \nsurveillance, including in \nAustralia, Canada, \nDenmark, France, \nGermany, India, Ireland, \nItaly, Netherlands, \nNew Zealand, South \nAfrica, Spain, Sweden, the \nUnited Kingdom, and the \nEuropean Union.\n*Australia: PAEDS, Denmark; SSI national registers, France: SI -VIC, Germany: SurvNet, India: NCRC, Ireland: HPSC, Italy: Sorvegl ianza Integrata COVID -19,Netherlands: NICE/RIVM, South \nAfrica: DATCOV, Spain: RENAVE, Sweden: FoHM national reporting, the United Kingdom: NHS COVID -19 Hospital Activity data, and the  European Union: ERVISS.\n2. Definition of hospitalizations due to COVID -19 used \nfor clinical analyses\nHow does COVID -NET define hospitalizations “due to COVID -19”?\n•“With” vs. “for” (due to) debate related to COVID -19 hospitalizations\n•Early in the pandemic, hospitals screened every patient when they arrived \nat the hospital\n•This captured hospitalizations among patients who tested positive for SARS -\nCoV-2 admitted for other reasons (e.g., surgery, labor and delivery)\n•To address this, COVID -NET developed an algorithm to identify cases for \nwhich COVID -19 was the likely primary reason for admission, hereafter \nreferred to as “hospitalizations due to COVID -19”\n-Algorithm uses chief complaint and history of present illness\n-Data for all current and previous surveillance periods back to March 2020 are \nposted monthly on public dashboard\nCOVID -NET Interactive Data Dashboard: https://www.cdc.gov/covid/php/covid -net/index.html  8\nWhy classifying hospitalizations as “with” or “due to” \nCOVID -19 is not simple\n•It can be difficult to identify a single cause for hospitalization\n•A positive SARS -CoV-2 test can influence the decision to admit someone \nwith medical conditions/comorbidities\n•Additionally, presence of medical conditions/comorbidities can influence \nthe decision to admit someone who tests positive\n•SARS -CoV-2 testing, treatment, discharge diagnosis codes, and other \nclinical data elements can all misclassify hospitalizations with respect to \nwhether or not they are due to COVID -19\n-ICD-10-CM codes in the U.S. are designed for administrative and billing purposes, not \nsurveillance, and may overcount or undercount\n‒COVID -19 code may be used just to indicate positive SARS -CoV-2 test*\n9ICD-10-CM: International Classification of Disease, Tenth Revision, Clinical Modification\n*ICD -10-CM Official Guidelines for Coding and Reporting FY 2025 -- UPDATED October 1, 2024 (October 1, 2024 - September 30, 2025 ): https://stacks.cdc.gov/view/cdc/158747 . Inpatient \nguidance: If the diagnosis documented at the time of discharge is qualified as “probable,” “suspected,” “likely,” “questionable,” “poss ible,” “still to be ruled out,” “compatible with,” \n“consistent with,” or other similar terms indicating uncertainty, code the condition as if it existed or was established.\nHow COVID -NET defines hospitalizations due to COVID -\n19 using likely primary reason for admission\n*Complaints with any attribution to specific/known etiology (i.e. appendicitis, imaging -\nidentified, substance abuse/overdose/withdrawal) or related to: trauma; biliary or \ncirrhosis; cancer/mass/leukemia/tumor; cellulitis/abscess/localized infection; foreign body, \ngenitourinary, back/extremity/joint pain, surgical complication, medication reaction, \npreeclampsia or gestational hypertension, ingestion/poisoning, medical device, scheduled \ntreatment/chemotherapy 10Is chief complaint/history of present \nillness (HPI) related to:\n•Obstetrics/labor and delivery\n•Inpatient surgery or procedure (e.g., \njoint or heart valve replacement)\n•Psychiatric admission needing acute \nmedical care\n•Trauma (e.g., car crash, fracture), or\n•Hospitalized at birth (newborn)?All laboratory -confirmed COVID -19–\nassociated hospitalizations Is chief complaint/ HPI reason for admission noted as:\n•Fever or respiratory illness\n•COVID -19–like illness, or\n•Suspicion for COVID -19?\nNO\nReason for admission reviewed by 2 physicians; \n3rd physician resolves disagreements\nYES\nEXCLUDENO\nIndicates SARS -CoV -2 was \nincidental finding or \nhospitalization unlikely \nrelated to COVID -19*Indicates \nhospitalization \nlikely related \nto COVID -19YES\nHospitalization due to \nCOVID -19\n87% of all recent hospitalizations among SARS -CoV-2-positive patients were \ndue to COVID -19 based on reason for admission\nData are posted publicly: https://www.cdc.gov/covid/php/covid -net/index.html . Likely reason for admission due to COVID -19 is defined as SARS -CoV-2-positive test ≤14 days before/during \nhospitalization AND chief complaint or history of present illness in medical record indicates fever, respiratory illness, COV ID-19-like illness, or suspicion for COVID -19-like illness. 1189\n69839187\n0102030405060708090100\n0–17 years 18–49 years 50–64 years ≥65 years OverallWeighted percent of COVID -NET hospitalizations\nAge groupPercent of COVID -19-associated hospitalizations due to COVID -19 based on reason \nfor admission, by age group and surveillance season —\nCOVID -NET, October 2022 –May 2025\n2022 –2023 2023 –2024 2024 –2025•Percent of COVID -19–associated \nhospitalizations due to COVID -19 \nhave increased over time\n•No longer widespread screening \nof asymptomatic patients\n•Percent of COVID -NET \nhospitalizations due to COVID -19 \nincreases with age among adults\n•Adults ages ≥65 years account for \n70% of COVID -19–associated \nhospitalizations, of which 91% are \nconsidered due to COVID -19 based \non reason for admission.70% of COVID -19–\nassociated hospitalizations\nHow COVID -NET goes beyond billing codes\n•Not all partner hospitals are able to provide final ICD -10-CM codes\n-Coding may be delayed or limited\n-Coding may be stored only in inaccessible billing systems\n•COVID -NET surveillance officers also review the discharge summary for each patient\n-Capture conditions that were not present at admission but developed during the hospital stay\n-Gives fuller picture of patient’s hospitalization and reduces some of the bias that comes from \nrelying only on billing codes\n12\nCOVID -NET hospitalizations classified as due to COVID -19 or \nwith COVID -19 using two different approaches\n1366,125 COVID -19 hospitalizations among patients of \nall ages during October 2023 –September 2024 \n7,279 (11%) random sample of  \nhospitalizations with chart review\n81% 52%\n88%\n*Respiratory -related defined as acute respiratory distress syndrome (ARDS), acute respiratory failure, asthma exacerbation, bron chiolitis, bronchitis, chronic obstructive pulmonary disorder (COPD) exacerbation, or \npneumonia as indicated by the abstracted condition from discharge summary or the presence of an ICD -10-CM discharge diagnosis co de.COVID -19 \nICD-10-CM \ncode\nCOVID -19 ICD -10-CM \ncode or sepsis or \nrespiratory -related* \ndischarge diagnosisSepsis or respiratory -\nrelated* discharge \ndiagnosis\nNeither COVID -19 ICD -\n10-CM code nor sepsis \nor respiratory -related* \ndischarge diagnosis12%ICD -10 codes and discharge diagnoses approach\n66,125 COVID -19 hospitalizations among patients of \nall ages during October 2023 –September 2024 \n7,279 (11%) random sample of  \nhospitalizations with chart review\n85%\nCOVID -19 likely \nreason for admission\nNon -COVID -19 reason \nfor admission15%COVID -NET reason for admission approach \n84% \nCOVID -19 \nICD-10-CM \ncode\n57% \nPulmonary \nor sepsis \ndischarge \ndiagnosis91% \nEither \nCOVID -19 \nICD-10-CM \ncode OR \npulmonary \nor sepsis \ndischarge \ndiagnosis64% \nCOVID -19 \nICD-10-CM \ncode\nKey Takeaways\n•Two approaches for defining hospitalizations due to COVID -19\n-COVID -19 identified as reason for admission\n-COVID -19-related discharge diagnoses\n•Similar proportions of patients classified using both methods:\n-88% had COVID -19 ICD -10-CM code or sepsis or respiratory diagnosis\n-85% identified by COVID -NET as COVID -19 being likely primary reason for admission \n•91% of hospitalizations using COVID -NET’s reason for admission approach had a COVID -19 ICD -10-CM \ncode or sepsis or respiratory diagnosis\n•COVID -NET’s reason for admission approach is more conservative than examining \ndischarge diagnoses\n•COVID -NET’s methods for identifying hospitalizations due to COVID -19 balances \ntimeliness, accuracy, and representativeness \n14\nPopulation -based rates of COVID -19–\nassociated hospitalizations\n15\nRates of COVID -19–associated hospitalization are \nhighest among the youngest and oldest age groups\nA COVID -19–associated hospitalization is defined as laboratory -confirmed SARS -CoV-2 in a person who (a) lives in a defined COVID -NET surveillance catchment area AND (b) tests positive \nfor SARS -CoV-2 (using a laboratory -based molecular, antigen or serology test) within 14 days before or during hospitalization. 16223\n117\n298 82774195653\n0100200300400500600700\n<6 months 6–11 months 1–4 years 5–11 years 12–17 years 18–49 years 50–64 years 65–74 years ≥75 yearsHospitalizations per 100,000 population\nAge groupPopulation -based COVID -19–associated hospitalization rates (per 100,000 population), by age group —\nCOVID -NET, October 2024 –September 2025\nRates are presented per 100,000 population and indicate the cumulative \n12-month age group -based risk of COVID -19–associated hospitalization.\nAmong adults hospitalized due to COVID -19, 15% were \nadmitted to the intensive care unit (ICU)\n1725\n1917\n14\n145\n051015202530\n0–17 years 18–49 years 50–64 years ≥65 yearsWeighted percent of hospitalizations\nAge groupWeighted percent (with 95% confidence intervals) of patients hospitalized due to COVID -19 with interventions \nand outcomes, by age group — COVID -NET, June 2024 –May 2025\nICU admission In-hospital death<1\nThe figure displays the proportion of adults hospitalized due to COVID -19 based on reason for admission with interventions and o utcomes, by age group — COVID -NET, June 2024 –May \n2025. Error bars denote 95% confidence intervals (95% CI).  Data are limited to hospitalizations where COVID -19 is a likely primary reason for admission. Deaths do not include other COVID -\n19-related deaths that might occur after a patient is discharged to hospice or deaths that occur soon after hospital discharge t hat could be attributable to COVID -19-related illness.During this period, 84% of all adults hospitalized due to COVID -19 who died in -hospital were ages ≥50 years. \nBurden of COVID -19-Associated \nHospitalizations among Infants\n18\nRates of respiratory virus -associated hospitalizations vary \nby age group and pathogen.\n1902004006008001000120014001600\n<1 1–4 5–11 12–17 18–49 50–64 65–74 ≥75Hospitalizations per 100,000 population\nAge group, in yearsCumulative rates of COVID -19–, influenza -, and respiratory syncytial virus \n(RSV) -associated hospitalizations — RESP -NET, October 2024 –September 2025\nCOVID-19 Influenza RSV\nRates for all three pathogens (COVID -19, influenza, and respiratory syncytial virus [RSV]) are laboratory -confirmed. Data source : https://www.cdc.gov/resp -net/dashboard/  \nNote that rates are not adjusted for testing or limited to admissions where the respiratory infection is the reason for admis sion.  Influenza surveillance was conducted October 2024 –April \n2025.\nCumulative COVID -19-associated hospitalization rates are highest \namong adults aged ≥75 years, followed by infants aged <6 months \nand adults ages 65 –74 years.\nWeekly rates of COVID -19–associated hospitalizations per 100,000 population by age group —COVID -NET, October 2024 –September 2025\nNote that rates are not adjusted for testing. Rates are not limited to admissions where the respiratory infection is the like ly primary reason for admission. 20050100150200250\nOct 2024 Nov 2024 Dec 2024 Jan 2025 Feb 2025 Mar 2025 Apr 2025 May 2025 Jun 2025 Jul 2025 Aug 2025 Sep 2025Hospitalizations per 100,000 population\nSurveillance week end date\n<6 months 6–11 months 1–4 years 5–11 years\n12–17 years 18–49 years 50–64 years 65–74 years50–64 years: \n1011–4 years:  29\n18–49 years: 27\n12–17 years: 8\n5–11 years: 8<6 months: 223\n65–74 years: 195\n6–11 months: 117\n50–64 years:  740200400600800Hospitalizations per \n100,000 population≥75 years: 653\nRelative risks of hospitalization due to \nCOVID -19 among adults by chronic \ncondition\n21\nBackground\n•Update to peer -reviewed manuscript by Ko, et al. published in Clinical \nInfectious Diseases  in 2021*\n* Ko J, Danielson ML, Town M, et al. Risk Factors for COVID -19-Associated Hospitalization: COVID -NET and BRFSS. https://doi.org/10.1093/cid/ciaa1419 . 22\n\nData Sources\n•COVID -NET (number of hospitalizations due to COVID -19)\n-October 2022 –September 2023\n-98 counties across 13 states\n•Behavioral Risk Factor Surveillance System (BRFSS) (chronic conditions)\n-Largest continuously conducted health survey system in the world (hundreds of \nthousands of interviews among community -dwelling U.S. adults each year)\n-2022 survey\n•National Center for Health Statistics (population data)\n-2020 U.S. Census data\n23\nOverview of the Analysis\n•Obtain weighted counts of persons hospitalized due to COVID -19 with and \nwithout underlying conditions (COVID -NET)\n-Limited to hospitalizations with COVID -19 as likely primary reason for admission\n-Limited to community -dwelling adults to match BRFSS parameters\n•Calculate weighted counts of community -dwelling adults with and \nwithout chronic diseases of interest in participating states (BRFSS)\n•Generate proportion of state population residing in the COVID -NET county \ncatchment area (Census)\n•Calculate adjusted rate ratios of hospitalization rates with vs. without \nchronic conditions\n24\nChronic conditions examined\n•Coronary artery disease\n•History of stroke\n•Diabetes mellitus\n•Chronic kidney disease\n•Chronic obstructive pulmonary disease (COPD)\n•Asthma \n•Obesity (body mass index [BMI] 30 –<40 kg/m²)\n•Severe obesity (BMI ≥40 kg/m²)\n•Current smoker\n25\nThe prevalence of most chronic conditions among adults \nhospitalized due to COVID -19 was generally higher than the \nprevalence observed in the general population.\nError bars denote 95% uncertainty intervals (95% CI). Obesity is defined as BMI 30 –<40 kg/m². Severe obesity is BMI ≥40 kg/m². 26\nWeighted prevalence (with 95% uncertainty intervals) of chronic medical conditions among adults \nhospitalized due to COVID -19 compared to community -dwelling adults in COVID -NET states, 2022 –2023Weighted prevalence (%)\nAmong adults, most chronic conditions examined \nincreased the risk of being hospitalized due to COVID -19\nCOPD: chronic obstructive pulmonary disease. Obesity is defined as BMI 30 –39 kg/m². Severe obesity is BMI ≥40 kg/m². Note that v ertical axis is presented in logarithmic scale. 27Rate ratio (with 95% uncertainty intervals) comparing rates of COVID -19 hospitalization among \ncommunity -dwelling adults with a chronic medical condition to those without, by age group — \nCOVID -NET states, October 2022 –September 2023\n•Risk conferred by \nseveral conditions \nappear to decline \nwith age (CAD, \ndiabetes, obesity). \nThis might be a \nconsequence of:\n•Inability to \nadjust for \ncomorbidities in \nthe models\n•Low population \nprevalence of \nsome conditions \nin some age \ngroups\nRisk for hospitalization due to COVID -19 increases \nwith the number of chronic conditions and age.\n§ Model includes number of conditions, age group, sex, and race or ethnicity group.\n¶ Number of conditions is a sum of chronic conditions (asthma, COPD, chronic kidney disease, coronary artery disease, diabete s, history of stroke, severe obesity, and current smoking). \nNote that vertical axis is presented in logarithmic scale. 28•Multiple chronic medical \nconditions and older age \nwere the strongest risk \nfactors for COVID -19 \nhospitalization among \nadults.\n•Hospitalization rates were \n18.5 -times as high among \nadults ages ≥75 years \ncompared to 18 –49 years.\n•The greatest risk factor \nexamined in this analysis\nStrengths and Limitations\n•Data are gathered from robust COVID -19 hospitalization public health \nsurveillance system\n•Ability to compare underlying conditions using state -level prevalence\n•Capability to examine and compare specific underlying conditions, \nprevalence of multiple conditions and age group as risk factors\n•Limitations\n-Results are preliminary and under review\n-Analysis is limited to community -dwelling adults\n-Adjustments for some comorbidities could not be made due to sparse data, \nespecially in younger groups.\n-Unable to look at differences in rate ratios across outcomes (e.g., ICU admission) \nor race and ethnicity categories due to sparse data in some categories.\n29", "summary": "Updates to COVID -19 epidemiology Advisory Committee on Immunization Practices September 19, 2025 1U.S. Centers for Disease Control and Prevention  COVID -NET monitors COVID -19 hospitalizations across  parts of the U.S. •RESP -NET includes COVID -NET, RSV -NET, FluSurv -NET •Collaboration between state and local health  departments and CDC •Includes data from >300 hospitals in 185 counties  across 13 states, covering about 10% of the U.S.  population COVID -NET:…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-september-18-19-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-09-18-19/02-Srinivasan-covid-508.pdf", "doc_date": "2025-09-18", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 29}
{"title": "03 srinivasan covid 508", "content": "COVID-19 Vaccination Implementation National Center for Immunization and Respiratory Di seases \nSeptember 19, 2025 Immunization Services Division Centers for Disease Control and Prevention \n•National Immunization Survey (NIS): \n-Random-digit-dial cellular telephone survey of adul ts age ≥18 years in the U.S. (all \n50 states, 5 local jurisdictions, and territories);  all responses are self reported. \n-Sample size: ~15,000 adult respondents weekly, ~60, 000 adult respondents monthly \n-Data are weighted to represent the non-institutiona lized U.S. population Data sources used to estimate U.S. immunization coverage \nCOVID-19 Vaccination Coverage \nNational Immunization Survey-Fall Respiratory Virus Module \n0.0 20.0 40.0 60.0 80.0 \n9/7/2024 \n9/14/2024 9/21/2024 9/28/2024 10/5/2024 \n10/12/2024 10/19/2024 10/26/2024 \n11/2/2024 11/9/2024 \n11/16/2024 11/23/2024 11/30/2024 \n12/7/2024 \n12/14/2024 12/21/2024 12/28/2024 \n1/4/2025 \n1/11/2025 1/18/2025 1/25/2025 \n2/1/2025 2/8/2025 \n2/15/2025 2/22/2025 \n3/1/2025 3/8/2025 \n3/15/2025 3/22/2025 3/29/2025 \n4/5/2025 \n4/12/2025 4/19/2025 4/26/2025 \nVaccination coverage (%) \nWeek ending date ≥65 years \n50-64 years \n18-49 years COVID-19 Vaccination Coverage (≥1 Dose) Among Adults 1 8-49 Years, 50-64 \nYears, and 65 Years and Older, 2024-2025 \nNational Immunization Survey National Immunization Survey National Immunization Survey National Immunization Survey- - --Fall Respiratory Virus Module Fall Respiratory Virus Module Fall Respiratory Virus Module Fall Respiratory Virus Module \n44.1 24.6 \n14.1 \n025 50 75 100 \nSep 7 \nSep 14 Sep 21 Sep 28 \nOct 5 \nOct 12 Oct 19 Oct 26 \nNov 2 Nov 9 \nNov 16 Nov 23 Nov 30 \nDec 7 \nDec 14 Dec 21 Dec 28 \nJan 4 \nJan 11 Jan 18 Jan 25 \nFeb 1 Feb 8 \nFeb 15 Feb 22 \nMar 1 Mar 8 \nMar 15 Mar 22 Mar 29 \nApr 5 \nApr 12 Apr 19 Apr 26 \nSep 7 \nSep 14 Sep 21 Sep 28 \nOct 5 \nOct 12 Oct 19 Oct 26 \nNov 2 Nov 9 \nNov 16 Nov 23 Nov 30 \nDec 7 \nDec 14 Dec 21 Dec 28 \nJan 4 \nJan 11 Jan 18 Jan 25 \nFeb 1 Feb 8 \nFeb 15 Feb 22 \nMar 1 Mar 8 \nMar 15 Mar 22 Mar 29 \nApr 5 \nApr 12 Apr 19 Apr 26 \nSep 7 \nSep 14 Sep 21 Sep 28 \nOct 5 \nOct 12 Oct 19 Oct 26 \nNov 2 Nov 9 \nNov 16 Nov 23 Nov 30 \nDec 7 \nDec 14 Dec 21 Dec 28 \nJan 4 \nJan 11 Jan 18 Jan 25 \nFeb 1 Feb 8 \nFeb 15 Feb 22 \nMar 1 Mar 8 \nMar 15 Mar 22 Mar 29 \nApr 5 \nApr 12 Apr 19 Apr 26 \nSep 7 \nSep 14 Sep 21 Sep 28 \nOct 5 \nOct 12 Oct 19 Oct 26 \nNov 2 Nov 9 \nNov 16 Nov 23 Nov 30 \nDec 7 \nDec 14 Dec 21 Dec 28 \nJan 4 \nJan 11 Jan 18 Jan 25 \nFeb 1 Feb 8 \nFeb 15 Feb 22 \nMar 1 Mar 8 \nMar 15 Mar 22 Mar 29 \nApr 5\nApr 12Apr 19Apr 26\n18-49 years 50-64 years 65-74 years ≥75 years Vaccination coverage (%) \n2024-25 season week ending date Vaccination coverage (2024-25) Vaccination coverage (2023-24) COVID-19 Vaccination Coverage (≥1 Dose) Among Adults  ≥18 Years, 65-\n74 Years, and ≥75 Years, 2023-24 and 2024-25 \nNational Immunization Survey-Fall Respiratory Virus  Module \n24.6 24.1 42.7 37.9 46.5\n38.3\n14.1 14.1 \n025 50 75 100 Vaccination coverage (%) \nWeek ending date Overall (6 months-17 years) 6 months-4 years 5-11 years 12-17 years COVID-19 Vaccination Coverage* Among Children 6 Mont hs–17 Years of \nAge, October 2024–April 2025, NIS-Flu \n* Up-to-date with the updated 2024–25 COVID-19 vacc ine is defined as receipt of at least one vaccinati on since August 22, 2024, for children ≥5 years; fo r children <5 years, up-to-\ndate status was defined based on the current recomm endations that also take into account number of dose s and brand of vaccine. Up-to-date status was deter mined by survey \nquestions on month and year of most recent COVID-19  vaccine, and for children <5 years, total number o f COVID-19 vaccinations received and brand of most recent COVID-19 \nvaccine. /uni2009\n2.4 16.6 10.5 0.8 1.4 9.9 8.1 \n0.0 10.0 20.0 30.0 40.0 50.0 60.0 18-49 (n=85) 50-64 (n=98) 18-64 (n=183) 65+ (n=172) Male (n=95) Female (n=257) Overall 18+ immunocompromised (n=355) \nWeighted % (95% CI) COVID-19 Vaccination Coverage (≥2 Doses) Among Adults 18 Years and Older \nWho Are Immunocompromised Who Received First Dose in August/September \n2024, as of End of March 2025 \nNational Immunization Survey National Immunization Survey National Immunization Survey National Immunization Survey- - --Fall Respiratory Virus Module Fall Respiratory Virus Module Fall Respiratory Virus Module Fall Respiratory Virus Module \n*Immunocompromised a dults were recommended to receive a second dose of 2 024-2025 COVID-19 vaccine \nsix months after their first dose .\n•COVID-19 vaccination coverage for older adults impro ved in 2024-2025 \ncompared to the previous season, but vaccination cover age for adults 18-\n64 years was similar between the 2023-2024 and 2024-20 25 seasons. \n•Approximately 13% of children between 6 months and 1 7 years of age \nwere up to date with COVID vaccination at the end o f April 2025. Summary \nPlace of COVID-19 Vaccination Among Adults 18 Years an d Older, 2024-2025 \nNational Immunization Survey National Immunization Survey National Immunization Survey National Immunization Survey- - --Fall Respiratory Virus Module Fall Respiratory Virus Module Fall Respiratory Virus Module Fall Respiratory Virus Module \n*Among persons who reported receiving a 2024-2025 CO VID-19 vaccination since August 22, 2024 (n=9,359).  Data collected April 1-27, 2025. 67.3 \n12.5 8.5 5.9 1.7 1.5 1.3 0.7 0.6 0.2 \n020 40 60 80 100 Weighted % (95% CI) Reported place of 2024-2025 COVID-19 vaccination, a dults age ≥18 years*, United States \nCOVID-19 Vaccination Coverage among Health Care Personnel \nNational Healthcare Safety Network \n•CDC’s National Healthcare Safety Network (NHSN) is the most widely used \nhealthcare associated infection tracking system and  provides important \nquality measures like healthcare personnel (HCP) va ccination status \n•CMS-certified healthcare facilities are required to  report monthly COVID-\n19 vaccination data and annual influenza vaccinatio n data for HCP \n•Across all healthcare facility types, the largest g roups of submitters are \nAcute Care Hospitals and Nursing Homes Estimating vaccination coverage through NHSN \nCOVID-19 and influenza vaccine coverage among healthcare personnel (HCP) 2022-2025* \n17 15 \n10 23 \n11 \n881 81 \n78 \n47 45 \n42 \n010 20 30 40 50 60 70 80 90 \n2 0 2 2 - 2 0 2 3 2 0 2 3 - 2 0 2 4 2 0 2 4 - 2 0 2 5 Vaccination Coverage (%) \nCOVID-19 vaccine coverage: Acute care hospital HCP COVID-19 vaccine coverage: Long term care HCP \nInfluenza vaccine coverage: Acute care hospital HCP Influenza vaccine coverage: Long term care HCP \nReferences: 1. Influenza and Up-to-Date COVID-19 Vaccination Co verage Among Health Care Personnel — National Healthc are Safety Network, United States, 2022–23 Influenz a Season | MMWR \n2. Influenza and COVID-19 Vaccination Coverage Among  Health Care Personnel — National Healthcare Safety Network, United States, 2023–24 Respiratory Virus S eason | MMWR \n*2024-2025 Data were collected from acute care hosp itals and nursing homes on HCP influenza and up-to-d ate COVID-19 vaccination coverage for the week ending  March 30, 2025. NHSN defined up-to-date COVID-19 vac cination during that \ntime as the receipt of ≥1 dose of a 2024–2025 COVID -19 vaccination. \nFor more information, contact CDC/ATSDR 1-800-CDC-INFO (232-4636) TTY:  1-888-232-6348    www.cdc.gov           www.a tsdr.cdc.gov \nThe findings and conclusions in this report are tho se of the authors and do not necessarily represent the official position \nof the Centers for Disease Control and Prevention a nd the Agency for Toxic Substances and Disease Regi stry. \nThank you", "summary": "COVID-19 Vaccination Implementation National Center for Immunization and Respiratory Di seases  September 19, 2025 Immunization Services Division Centers for Disease Control and Prevention  •National Immunization Survey (NIS):  -Random-digit-dial cellular telephone survey of adul ts age ≥18 years in the U.S. (all  50 states, 5 local jurisdictions, and territories);  all responses are self reported.  -Sample size: ~15,000 adult respondents weekly, ~60, 000 adult respondents monthly  -Data are…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-september-18-19-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-09-18-19/03-srinivasan-covid-508.pdf", "doc_date": "2025-09-18", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 13}
{"title": "04 Srinivasan covid 508", "content": "Updates to COVID -19 Vaccine Effectiveness\nAdvisory Committee on Immunization Practices\nSeptember 19, 2025National Center for Immunization and Respiratory Diseases \n\n2•Vaccine effectiveness methods\n•Estimates of COVID -19 Vaccine Effectiveness in Children\n•Estimates of Maternal COVID -19 Vaccine Effectiveness\n•Estimates of COVID -19 Vaccine Effectiveness in Adults\n•ConclusionsAgenda –COVID -19 vaccine effectiveness (VE)\nVaccine effectiveness methods\n3\nRandomized clinical trials vs. real -world evidence\n•Randomized clinical trials needed to demonstrate vaccine efficacy for licensure of \nnew vaccines : does vaccination prevent disease under ideal and controlled \nconditions (i.e., placebo or vaccine comparator )?\n•Observational studies provide real -world evidence of vaccine effectiveness : does \nvaccination protect against disease in the population?\n•Vaccine effectiveness measures benefit of current* vaccination in a population with \nexisting levels of protection due to prior infection, vaccination, or both.    \n4* Varies by pathogen. “Current” for COVID -19 or influenza would indicate this season’s vaccine.\nEfficacy and effectiveness are population level \nestimates.\n•If a vaccine has an effectiveness of 80%:\n-It does not mean that the vaccine will only work 80% of the time.\n-It does mean that in a vaccinated population, 80% fewer people will have the \noutcome of interest when they are exposed to the virus compared to an \nunvaccinated population.\nVaccine effectiveness can be measured using study \ndesigns across a spectrum\nCase -control\nControls generally sampled from \nthe same population* that gave \nrise to the casesTest -negative design (TND)\nControls can be sampled or include entire \neligible at -risk population.*\nSometimes referred to as a\n“case -cohort” design.Cohort\nEligible at -risk population* are \nfollowed to see who develops or \ndoes not develop disease\n•A vaccine effectiveness (VE) study measures the extent to which a vaccine reduces the incidence of a \nspecific disease or its severe outcomes in a vaccinated population compared to an unvaccinated \npopulation, often expressed as a percentage reduction in disease occurrence. \n•VE can be measured using risk ratio, rate ratio, hazard ratio, or odds ratio, usually after adjustment for \nconfounding.\n* Population is generally chosen from geographic or hospital -based enrollment.\n7\nCaseControlPerson with acute\nrespiratory illness\nSARS -CoV-2 test\nCOVID -19 \nvaccination status\nFor respiratory viruses, CDC primarily uses the test -negative design (TND), to \nmeasure vaccine effectiveness (VE)\nEffectiveness = 1 – (odds ratio ) x 100%    Odds ratio = 𝑂𝑑𝑑𝑠  𝑜𝑓 𝑣𝑎𝑐𝑐𝑖𝑛𝑎𝑡𝑖𝑜𝑛 𝑐𝑎𝑠𝑒𝑠\n𝑂𝑑𝑑𝑠  𝑜𝑓 𝑣𝑎𝑐𝑐𝑖𝑛𝑎𝑡𝑖𝑜𝑛 𝑐𝑜𝑛𝑡𝑟𝑜𝑙𝑠\nVE findings should be interpreted as the \nadded benefit provided by COVID -19 \nvaccination in a population with a high \nprevalence of vaccine - and infection -induced \nimmunity.\n8Vaccine effectiveness can be measured using study designs across a \nspectrum\nCase -control\nControls generally sampled from \nthe same population* that gave \nrise to the casesTest -negative design (TND)\nControls can be sampled or include entire \neligible at -risk population.*\nSometimes referred to as a “case -cohort” \ndesign.Cohort\nEligible at -risk population* are \nfollowed to see who develops or \ndoes not develop disease\n* Population is generally chosen from geographic or hospital -based enrollment.Strengths\n• More cost effective than cohorts\n• Useful for rare outcomes\nLimitations\n• Retrospective nature can introduce \nrecall bias (specific to studies that \ncollect information ONLY through \ninterview) \n• If controls are sampled from \ncommunity, misclassification bias can \nbe introduced (no test to confirm \nnegative status)\n• Potential for confounding due to \nhealth -seeking behaviors\n• Residual confounding is possible\n• Difficult to establish causalityStrengths\n• Useful for rare outcomes\n• Controls for health -seeking behavior \nand exposure risk\n• Efficient for assessing VE in real -world \nsettings, including against new variants\n• Efficient use of resources , especially \nwhen electronic health data are used\nLimitations\n• Requires accurate testing and \nclassification (as with all studies)\n• Residual confounding is possible\n• Difficult to establish causalityStrengths\n• Allows for assessment of multiple \noutcomes\nLimitations\n• Time -consuming and expensive\n• If identification of outcomes requires \nseeking medical care, misclassification \nbias can be introduced\n• Potential for confounding due to \nhealth -seeking behaviors\n• Residual confounding is possible\n• Difficult to establish causality\n9VISION Multi -Site Network of Electronic Health Records\n>300 emergency departments and urgent cares clinics and >200 hospitals \n▪Design: Test-negative design\n▪Population: Persons visiting a participating emergency \ndepartment or urgent care or hospitalized with COVID -\n19-like illness with a SARS -CoV-2 test result within 10 \ndays before or 72 hours after encounter\n−Cases : CLI with positive  NAAT or antigen for SARS -CoV-2 \nand no positive NAAT for RSV or influenza\n−Controls : CLI with negative  NAAT for SARS -CoV-2 and no \npositive NAAT for influenza or RSV (≥60 years)\n▪Vaccination data: Documented by electronic health records and state and city registries\nCLI = COVID -19-like illness; ED/UC = emergency department/urgent care; RSV = respiratory syncytial virus; NAAT = nucleic acid am plification test\nCLI is defined based on the presence of specific discharge diagnosis codes. Additional methods available: Link -Gelles, et al. MM WR. \nhttps://www.cdc.gov/mmwr/volumes/74/wr/mm7406a1.htm    \n10\n•Case infants: hospitalized for COVID -19 as the primary reason \nfor admission and with a positive SARS -CoV-2 NAAT or antigen \ntest result\n•Control infants: hospitalized for COVID -19-like illness and \nnegative SARS -CoV-2 NAAT result, matched to case infants by \nsite; hospitalized within 4 weeks of case infant admissionOvercoming COVID -19 Network\n•Design: Case -control study to assess \neffectiveness of maternal vaccination against \nCOVID -19-related hospitalizations in infants \n<6 months of age\n•Population: 26 pediatric hospitals in 20 \nstates\n•Data collection: Baseline demographic and \nclinical characteristics obtained via chart \nabstraction and parent interview\n•Vaccination status: Maternal vaccination \nstatus verified using state vaccination \nregistries, electronic medical records, or \nother sources\n10\n11IVY Network —26 hospitals, 20 U.S. States\n•Design : Test -negative, case -control design\n•Population : Adults  ages  ≥18 years  hospitalized with COVID -19-\nlike illness* and SARS -CoV-2 test results within 10 days of \nillness onset and 3 days of admission\n–Cases: CLI and test  positive  for SARS -CoV-2 by NAAT or antigen\n–Controls : CLI and test negative  for SARS -CoV-2, influenza (≥18 \nyears) and RSV (≥60 years) by RT -PCR\n•Vaccination data: Electronic medical records, state and city \nregistries, and plausible self -report\n•Specimens: Nasal swabs  obtained on all patients for central \nRT-PCR testing and whole genome sequencing\n*COVID -19-like illness = CLI; CLI is defined as presence of any one of the following: fever, cough, shortness of breath, chest i maging consistent with pneumonia, or hypoxemia\nNAAT = nucleic acid amplification test\n\n12Measuring COVID -19 Vaccine Effectiveness (VE)\nMeasure Definition* Example \nvaccinated\ngroupExample comparison group\nAbsolute VE Compares frequency of health outcomes in \nvaccinated and unvaccinated people Received original \nmonovalent doseReceived no COVID -19 vaccines ever\nRelative VE Compares frequency of health outcomes in \npeople who received one type of vaccine to \npeople who received a different vaccineReceived  bivalent \ndoseEligible for, but did not receive, \nbivalent COVID -19 vaccine , but \nreceived original monovalent dose\nVE “seasonal” \nCOVID -19 vaccinesCompares people who received this \n“season’s”  COVID -19 vaccine to people who \ndid not, regardless of past COVID -19 \nvaccinationReceived\n this “season’s”Eligible for, but did not receive, this \n“season’s” , regardless of past COVID -\n19 vaccination history \n* Prior SARS -CoV-2 infection is not generally considered, as it is documented inconsistently in medical records.\nEstimates of COVID -19 Vaccine \nEffectiveness in Children\n13\n14Age group | COVID -19 vaccination statusTotal\nencountersSARS -CoV -2-\ntest -positive, N (%)Median interval \nsince\nlast dose among\nthose vaccinated,\ndays (IQR) Adjusted vaccine effectiveness % (95% CI)\nNo updated 2023 -2024 COVID -19 vaccine dose*\n9 months -4 years 43,246 1,886 (4) 367 (250 to 461) Ref\n5-17 years 54,310 2,071 (4) 679 (491 to 810) Ref\n≥18 years 279,733 31,167 (11) 756 (61 -189) Ref\n2023 -2024 COVID -19 dose received 7 -59 days earlier\n9 months -4 years 725 18 (2) 32 (20 to 46) 53 (24 to 70)\n5-17 years 951 16 (2) 34 (19 to 47) 64 (41 to 78)\n≥18 years 16,082 1,228 (8) 34 (21 -47) 49 (46 to 52)\n2023 -2024 COVID -19 dose received 60 -299 days earlier\n9 months -4 years 1,345 48 (4) 129 (91 to 178) 23 ( -4 to 43)\n5-17 years 2,510 63 (3) 138 (100 to 185) 34 (14 to 49)\n≥18 years 49,824 4,701 (9) 149 (100 -211) 12 (8 to 15)VE of 2023 –2024 COVID -19 vaccine  doses against emergency \ndepartment/urgent care encounters  — VISION\nSeptember 2023 – August 2024\n-20 0 20 40 60 80 100\nCDC, unpublished data\n* Includes all individuals who did not receive a 2023 -2024 COVID -19 vaccine. For those aged ≥5 years, this includes unvaccinated  persons and persons who were vaccinated with ≥1 original \nmonovalent or bivalent COVID -19 doses. For those aged <5 years, children with a partial initial series were excluded. The 2023 -2024 dose could have been part of the initial series or in addition to \nthe initial series.\nVaccine effectiveness was calculated by comparing the odds of COVID -19 vaccination in case -patients and control -patients using t he equation: (1 – adjusted odds ratio) x 100%. Odds \nratios were estimated by multivariable logistic regression. The odds ratio was adjusted for age, sex, race and ethnicity, cal end ar day, and geographic region. \n15Age group | COVID -19 vaccination statusTotal\nencountersSARS -CoV -2-\ntest -positive, N (%)Median interval \nsince\nlast dose among\nthose vaccinated,\ndays (IQR) Adjusted vaccine effectiveness % (95% CI)\nNo updated 2024 -2025 COVID -19 vaccine dose*\n9 months -4 years 31,060 809 (3) 392 (282 -662) Ref\n5-17 years 38,870 926 (2) 972 (710 -1,116) Ref\n≥18 years 200,933 12,927 (6) 1,068 (742 -1,224) Ref\n2024 -2025 COVID -19 dose received 7 -179 days earlier\n9 months -4 years 393 2 (1) 64 (30 -98) 79 (17 to 95)\n5-17 years 2,208 22 (1) 81 (44 -122) 57 (33 to 72)\n≥18 years 40,043 1,694 (4) 89 (50 -129) 34 (30 to 37)VE of 2024 -2025 COVID -19 vaccine  doses against emergency \ndepartment/urgent care encounters  — VISION\nSeptember 2024 – May 2025\n-20 0 20 40 60 80 100\nCDC, unpublished data\n* Includes all individuals who did not receive a 2024 -2025 COVID -19 vaccine. For those aged ≥5 years, this includes unvaccinated  persons and persons who were vaccinated with ≥1 original \nmonovalent or bivalent COVID -19 doses. For those aged <5 years, children with a partial initial series were excluded . The 2024 -2025 dose could have been part of the initial series or in addition to \nthe initial series.\nVaccine effectiveness was calculated by comparing the odds of COVID -19 vaccination in case -patients and control -patients using t he equation: (1 – adjusted odds ratio) x 100%. Odds \nratios were estimated by multivariable logistic regression. The odds ratio was adjusted for age, sex, race and ethnicity, cal end ar day, and geographic region.\nEstimates of Maternal COVID -19 Vaccine \nEffectiveness\n16\nVISION: VE of 2023 -2024  COVID -19 vaccination against COVID -19–associated \nemergency department/urgent care encounters among immuno competent  \nwomen aged 18 -45 years, by pregnancy status  — VISION\nSeptember 2023 – August 2024\nVE=vaccine effectiveness; CLI = COVID -19-like illness\nVaccine effectiveness was calculated by comparing the odds of COVID -19 vaccination in case -patients and control -patients using t he equation: (1 – adjusted odds ratio) x 100%. Odds \nratios were estimated by multivariable logistic regression. The odds ratio was adjusted for: age, ethnicity, race, underlying  medical conditions, gestational age at encounter, site, \nMedicaid status, day of encounter, site facility urbanicity\nCDC unpublished data17Vaccine Dosage PatternTotal\ntestsSARS -CoV-2-\ntest-positive,\nN (%)Median interval\nsince last dose,\ndays (IQR)Adjusted VE\n(95% CI)\nPregnant at CLI encounter\nNo 2023 -2024 dose (ref) 5058 709 (14) 797 (648, 931) Ref\nMost recent 2023 -2024 dose received 7 -179 days 229 13 (6) 77 (44, 120) 58 (24 -77)\nNot pregnant at CLI encounter\nNo 2023 -2024 dose (ref) 76,636 8,052 (11) 794 (641, 931) Ref\nMost recent 2023 -2024 dose received 7 -179 days 5,079 313 (6) 83 (45, 126) 37 (29 -44)\n-20 0 20 40 60 80 100\nVaccine Effectiveness (%)\nOvercoming COVID -19: Effectiveness* of maternal vaccination† in \nprevention of COVID -19–associated hospitalization  among infants§\nMarch 9, 2022 – May 31, 2023\nSimeone & Zambrano et al., MMWR, 2023: https://www.cdc.gov/mmwr/volumes/72/wr/mm7239a3.htm . \n* VE estimates were based on odds of maternal vaccination during pregnancy in case -patients versus control patients, adjusted fo r U.S. Census Bureau region, admission date (monthly), age (in months), \nsex, and race and ethnicity (non -Hispanic Black or African American, non -Hispanic White, non -Hispanic other, Hispanic or Latino of any race, or unknown). Study site was included as a repeated effect. VE \nwas calculated as (1 – adjusted odds ratio) x 100%.\n†Maternal vaccination status was based on the last date of a COVID -19 mRNA vaccine dose: unvaccinated was defined as mothers who  had not received any vaccine dose before or during pregnancy, \nand vaccinated was defined as mothers who received their last dose of a COVID -19 mRNA vaccine between the first day of pregnancy  and 14 days before delivery. Among those vaccinated during \npregnancy, mothers could have received ≥1 dose during pregnancy. Mothers could receive 1 dose of Ad.26.CoV2.S (Janssen [Johns on & Johnson]) vaccine before or during pregnancy and 1 dose of an \nmRNA vaccine during pregnancy. Mothers who received only 1 dose of an mRNA vaccine were considered partially vaccinated and w ere excluded from the analysis. Mothers whose last vaccine dose \noccurred before pregnancy were excluded from the analysis.\n§Infants were excluded from analysis if they were born to mothers who had received their most recent dose before pregnancy, re ceived only 1 dose of an mRNA vaccine, received their most recent \nvaccine dose within 14 days of delivery, received only 1 dose of a viral vector vaccine, or whose vaccination status could no t be verified or whose timing of vaccination was unknown.18Age group of infantNo. vaccinated/Total no. (%)\nInterval between last vaccine dose and infant \nhospitalization, days (IQR)Effectiveness of Maternal Vaccination against Infant Covid -19 \nHospitalization % (95% CI) Case -patients Control patients\n0-5 months 82/377 (22) 94/339 (28) 236 (185 –300) 35 (15 –51)\n0-2 months 43/227 (19) 63/214 (29) 219 (152 –264) 54 (32 –68)\n0 20 40 60 80 100\nVaccine Effectiveness (%)\nEstimates of COVID -19 Vaccine \nEffectiveness in Adults\n19\n20Effectiveness of 2024–2025 COVID -19 vaccination against COVID -19–associated hospitalization  \namong immunocompetent  adults aged ≥65 years — VISION and IVY Networks\nSeptember 2024 – May 2025\nNetwork/2024 -2025 COVID -19 vaccination status/days \nsince doseCOVID -19 \ncase -\npatients\nN (Col %)COVID -19 \ncontrol -\npatients\nN (Col %)Median interval since\nlast dose among\nvaccinated*, days (IQR) Adjusted vaccine effectiveness % (95% CI)\nVISION\nNo 2024 -2025 COVID -19 dose  (Ref) 2,943 (85) 34,900 (74) 958 (508 -1,187) Ref\nReceived 2024 -2025 COVID -19 dose 7–179 days earlier 515 (15) 12,043 (26) 92 (51 -132) 44 (38 -50)\n2024 -2025 COVID -19 dose , 7–59 days earlier 155 (4) 3,604 (8) 34 (20 -47) 46 (36 -54)\n2024 -2025 COVID -19 dose , 60–119 days earlier 207 (6) 4,509 (10) 90 (75 -104) 50 (42 -57)\n2024 -2025 COVID -19 dose , 120 –179 days earlier 153 (4) 3,930 (8) 147 (133 -162) 32 (19 -43)\nIVY\nNo 2024 -2025 COVID -19 dose  (Ref) 822 (88) 1,824 (79) Not available Ref\nReceived 2024 -2025 COVID -19 dose 7–179 days earlier 110 (12) 499 (21) 92 (55 –130) 46 (32 -58)\n2024 -2025 COVID -19 dose , 7–59 days earlier 43 (5) 124 (5) 32 (20 –46) 42 (16 -60)\n2024 -2025 COVID -19 dose , 60–119 days earlier 37 (4) 205 (9) 89 (73 –103) 53 (32 -68) \n2024 -2025 COVID -19 dose , 120 –179 days earlier 30 (3) 170 (7) 146 (130 –161) 40 (9 -62)\n0 20 40 60 80 100\nVaccine effectiveness (%)\nUpdated from: Link -Gelles, et al. MMWR: https://www.cdc.gov/mmwr/volumes/74/wr/mm7406a1.htm   \nVaccine effectiveness was calculated by comparing the odds of 2024 –2025 COVID -19 vaccination in case -patients and control -patien ts using the equation: (1 – adjusted odds ratio) x 100%. Odds ratios \nwere estimated by multivariable logistic regression. For VISION, the odds ratio was adjusted for age, sex, race and ethnicity , calendar day, and geographic region. For IVY, the odds ratio was adjusted for \nage, sex, race and ethnicity, geographic region (U.S. Department of Health and Human Services Region) and calendar time (biwe ekly intervals). The “no 2024 –2025 dose” group included all eligible \npersons who did not receive a 2024 –2025 COVID -19 vaccine dose, regardless of number of previous COVID -19 vaccine doses. VISION data go through May 2025; IVY data go through April 2025.\n*Time since vaccination is for most recent dose, which could have been an original monovalent, bivalent, 2023 -2024, or 2024 -2025  COVID -19 vaccine.\n21Effectiveness of 2024–2025 COVID -19 vaccination against COVID -19–associated critical illness  \namong immunocompetent  adults aged ≥65 years — VISION and IVY Networks\nSeptember 2024 – May 2025\n2024 -2025 COVID -19 vaccination status/days since \ndoseCOVID -19 \ncase -\npatients\nN (Col %)COVID -19 \ncontrol -\npatients\nN (Col %)Median interval since\nlast dose among\nvaccinated*, days (IQR) Adjusted vaccine effectiveness % (95% CI)\nVISION\nNo 2024 -2025 COVID -19 dose  (Ref) 558 (85) 34,900 (74) 961 (510 -1,189) Ref\nReceived 2024 -2025 COVID -19 dose 7–179 days earlier 97 (15) 12,043 (26) 92 (51 -132) 45 (31 -56)\n2024 -2025 COVID -19 dose , 7–59 days earlier 28 (4) 3,604 (8) 34 (20 -47) 46 (21 -64)\n2024 -2025 COVID -19 dose , 60–119 days earlier 44 (7) 4,509 (10) 90 (75 -104) 45 (25 -60)\n2024 -2025 COVID -19 dose , 120 –179 days earlier 25 (4) 3,930 (8) 147 (133 -162) 43 (13 -62)\nIVY\nAcute respiratory failure\nNo 2024 -2025 COVID -19 dose  (Ref) 158 (88) 1,817 (78) Not available Ref\nReceived 2024 -2025 COVID -19 dose 7–179 days earlier 21 (12) 498 (22) 96 (59 -131) 44 (11 -67)\nICU admission or death\nNo 2024 -2025 COVID -19 dose  (Ref) 141 (91) 1,824 (79) Not available Ref\nReceived 2024 -2025 COVID -19 dose 7–179 days earlier 14 (9) 499 (21) 96 (60 -133) 56 (23 -76)\nInvasive mechanical ventilation or death\nNo 2024 -2025 COVID -19 dose  (Ref) 74 (94) 1,824 (79) Not available Ref\nReceived 2024 -2025 COVID -19 dose 7–179 days earlier 5 (6) 499 (21) 97 (60 -133) 70 (35 -89)\n0 20 40 60 80 100\nVaccine effectiveness (%)\nBased on methods in: Link -Gelles, et al. MMWR: https://www.cdc.gov/mmwr/volumes/74/wr/mm7406a1.htm   \nVaccine effectiveness was calculated by comparing the odds of 2024 –2025 COVID -19 vaccination in case -patients and control -patien ts using the equation: (1 – adjusted odds ratio) x 100%. Odds ratios were estimated by multivariable logistic regression. For VI SION, the \nodds ratio was adjusted for age, sex, race and ethnicity, calendar day, and geographic region. For IVY, the odds ratio was ad justed for age, sex, race and ethnicity, geographic region (U.S. Department of Health and Human Services Region) and calendar ti me (biweekly \nintervals). The “no 2024 –2025 dose” group included all eligible persons who did not receive a 2024 –2025 COVID -19 vaccine dose, r egardless of number of previous COVID -19 vaccine doses. VISION data go through May 2025; IVY data go through April 2025.\nFor VISION, critical illness is defined as admission to the intensive care unit or in -hospital death. For IVY, acute respiratory  failure was defined as new receipt of high -flow nasal canula, noninvasive ventilation, or invasive mechanical ventilation.\n*Time since vaccination is for most recent dose, which could have been an original monovalent, bivalent, 2023 -2024, or 2024 -2025  COVID -19 vaccine.\nICU = intensive care unit\n22Effectiveness of 2024–2025 COVID -19 vaccination against COVID -19–associated hospitalization  \namong immunocompromised  adults aged ≥65 years — VISION and IVY Networks\nSeptember 2024 – May 2025\nNetwork/2024 -2025 COVID -19 vaccination status/days \nsince doseCOVID -19 \ncase -\npatients\nN (Col %)COVID -19 \ncontrol -\npatients\nN (Col %)Median interval since\nlast dose among\nvaccinated*, days (IQR) Adjusted vaccine effectiveness % (95% CI)\nVISION\nNo 2024 -2025 COVID -19 dose  (Ref) 719 (81) 10,035 (69) 882 (451 -1,166) Ref\nReceived 2024 -2025 COVID -19 dose 7–179 days earlier 164 (19) 4,432 (31) 93 (53 -133) 38 (25 -48)\n2024 -2025 COVID -19 dose , 7–59 days earlier 62 (7) 1,247 (9) 35 (20 -47) 25 (2 -43)\n2024 -2025 COVID -19 dose , 60–119 days earlier 61 (7) 1,689 (12) 89 (75 -104) 47 (30 -60)\n2024 -2025 COVID -19 dose , 120 –179 days earlier 41 (5) 1,496 (10) 147 (133 -163) 39 (14 -57)\nIVY\nNo 2024 -2025 COVID -19 dose  (Ref) 214 (83) 670 (76) Not available Ref\nReceived 2024 -2025 COVID -19 dose 7–179 days earlier 44 (17) 209 (24) 82 (48 -133) 36 (6 -57) \n0 20 40 60 80 100\nVaccine effectiveness (%)\nUpdated from: Link -Gelles, et al. MMWR: https://www.cdc.gov/mmwr/volumes/74/wr/mm7406a1.htm  \nVaccine effectiveness was calculated by comparing the odds of 2024 –2025 COVID -19 vaccination in case -patients and control -patien ts using the equation: (1 – adjusted odds ratio) x 100%. Odds \nratios were estimated by multivariable logistic regression. For VISION, the odds ratio was adjusted for age, sex, race and et hnicity, calendar day, and geographic region. For IVY, the odds ratio was \nadjusted for age, sex, race and ethnicity, geographic region (U.S. Department of Health and Human Services Region) and calend ar time (biweekly intervals). The “no 2024 –2025 dose” group included \nall eligible persons who did not receive a 2024 –2025 COVID -19 vaccine dose, regardless of number of previous COVID -19 vaccine do ses (if any) received. VISION data go through May 2025; IVY data \ngo through April 2025.\n* Time since vaccination is for most recent dose, which could have been an original monovalent, bivalent, 2023 -2024, or 2024 -2025 COVID -19 vaccine.\n23•For the respective year, compared to no in -season dose, COVID -19 vaccination provided additional protection \nagainst:\n-COVID -19-associated emergency department and urgent care* visits among children ; protection was similar across age groups.\n-COVID -19-associated emergency department and urgent care visits among adults (data included in back -up).\n-COVID -19-associated hospitalizations among adults aged ≥65 years with and without immunocompromising conditions .\n-COVID -19-associated critical illness among adults aged ≥65 years ; protection appeared to be higher and more durable against \ncritical illness compared to less severe outcomes.\n•VE should be interpreted as the added benefit of 2023 –2024 or 2024 –2025 COVID -19 vaccination in a population with \nhigh levels of infection -induced immunity, vaccine -induced immunity, or both.    \n-Prior SARS -CoV-2 infection contributes protection against future disease, though protection wanes over time. \n-An increase in SARS -CoV-2 circulation in the United States during late summer 2024, just before the 2024 –2025 COVID -19 vaccines \nwere approved and authorized, may have resulted in higher population -level immunity against JN.1 -lineage strains, which could \nhave resulted in lower measured VE than in a population with less recent infection.Conclusions: effectiveness of COVID -19 vaccines\n* Due to lower baseline rates of severe disease and lower COVID -19 vaccine coverage, VE against hospitalization and critical ill ness in children could not be estimated.\n24Data and analysis were provided by CDC and the \nfollowing CDC -funded network partners:\nVISION Collaborators\nIVY Collaborators\nOvercoming Collaborators\nBack -up\n26\nConclusions: “TND provided \nreliable inferences on COVID -19 \nvaccine effectiveness in health \ncare–seeking populations for \nmultiple vaccines and symptom \ndefinitions”\nSource: Andrews L et al, JAMA Network Open 2025\nEvaluating the Test -Negative Design for COVID -19 Vaccine \nEffectiveness Using Randomized Trial Data: A Secondary Cross -\nProtocol Analysis of 5 Randomized Clinical Trials - PubMedEstimates based on RCT vs TND analysis\nCCC = concordance correlation coefficient\nSteps from vaccine licensure to recommendations and \npost -licensure monitoring and evaluation\n* Academic, private and public healthcare, non -profit partnersManufacturers\n•Safety, \nimmunogenicity, and \nefficacy\n•Request to FDA for \nEmergency Use \nAuthorization (EUA) \nor Biologics Licensure \nApplication (BLA)FDA\n•Review of evidence \nfor licensure\n•Advised by VRBPACCDC\n•Review of safety, \nefficacy, disease \nburden, risks, \nbenefits, costs\n•Advised by ACIP\n•Makes \nrecommendations for \nuse of vaccinations in \nspecific populationsCDC & others*\n•Real -world evidence\n•Safety monitoring\n•Vaccine effectiveness\n•Impact of vaccination \n(effect on disease \nburden)\nMix of pre -clinical and clinical data Primarily clinical data\nOutcome Analysis Design Vaccine efficacy /effectiveness,  % (95% CI)\nSymptomatic, RSV -\nassociated lower\nrespiratory tract\ndisease (LRTD)GSK trial (≥2 or 3 sx LRTD, primary endpoint)†RCT 83 (58 –94)\nPfizer trial (≥2 sx LRTI, co -primary endpoint) * RCT 67 (29 –86) \nPfizer trial (≥3 sx LRTI, co -primary endpoint) * RCT 86 (32 –99)\nRSV -associated\nhospitalizationIVY Network, adults ≥60 years§TND 75 (50 –87)\nVISION, adults ≥60 years, immunocompetent TND 80 (71 –85)\nVHA, adults ≥60 years§Cohort 82 (69 –89) \nMedicare ESRD, otherwise immunocompetent, ≥65y Cohort 72 (41 -87)\nVISION, immunocompromised TND 73 (48 –85)\nMedicare ESRD, additional immunocompromise, ≥65y Cohort 83 (45 -95)Observational VE studies show RSV vaccines protect against severe RSV \ndisease, similar to results from trials, although endpoints differ\n0 20 40 60 80 100\nVaccine effectiveness, % (95% CI)\n† Papi  A, et. al. Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older Adults. N Engl J Med . 2023;388:595 –608.  See slide 43 for detailed definitions. \n* Walsh E, et. al. Efficacy and Safety of a Bivalent RSV Prefusion F Vaccine in Older Adults. N Engl J Med . 2023;388:1465 –77.  See slide 43 for detailed definitions.\n§ Includes patients with immunocompromising conditions in the displayed VE estimate.Abbreviations:  ESRD = End stage renal disease; LRTI = lower respiratory tract infection; LRTD = lower respiratory tract disease; sx = symptoms or signs; \ny = years; RCT = randomized controlled trial; TND = test -negative design\nData originally presented at \nJune 2024 ACIP meeting.\nObservational COVID -19 VE studies conducted pre -Delta (March -\nApril/May 2021) showed COVID -19 vaccines provided similar protection \nto estimates from trials for symptomatic SARS -CoV-2 infection\nAnalysis Design Vaccine efficacy /effectiveness,  % (95% CI)\nPfizer, median 2 months after 2nd dose RCT 95.0 (90.3 -97.6)\nModerna, median 63 days after 2nd dose RCT 94.1 (89.3 -96.8)\nICATT Pfizer, 14 -60 days after 2nd dose TND 90 (89 -91)\nICATT Moderna, 14 -60 days after 2nd dose TND 95 (95 -96)\nHEROES -RECOVER, median 69 days after 2nd dose Cohort 91 (76 -97)\nICATT = Increasing Community Access to Testing, which is a CDC -funded program to provide SARS -CoV-2 testing in retail pharmacies . ICATT uses a test -negative design.\nPolack et al., NEJM, 2020: https://www.nejm.org/doi/full/10.1056/NEJMoa2034577  \nBaden et al., NEJM, 2020: https://www.nejm.org/doi/full/10.1056/NEJMoa2035389  \nBritton et al., JAMA, 2022: https://jamanetwork.com/journals/jama/fullarticle/2789294  \nThompson et al., NEJM, 2021: https://www.nejm.org/doi/full/10.1056/NEJMoa2107058  0 20 40 60 80 100\nVaccine effectiveness, % (95% CI)\n30COVID -19 Vaccination Coverage Among Children and Adolescents 6 Months -17 \nYears, by Season and Age Group, National Immunization Survey, 2023 -2025\nWeekly estimates of COVID -19 vaccination coverage for vaccination among children through December 31, 2023, were calculated usin g data from the National Immunization Survey –Child COVID Module (NIS –\nCCM) . The NIS –CCM was discontinued at the end of 2023 and questions regarding COVID -19 vaccination status and intent were added to t heNational Immunization Survey –Flu (NIS–Flu).\nNIS–CCM and NIS –Flu are national random -digit dial cellular telephone surveys of households with children ages 6 months through 17 years; NIS –Flu is conducted during October -June. The respondent to a NIS –\nFlu survey is a parent or guardian who said they were knowledgeable about the child's vaccination history. All estimates are based upon parental report of receipt of vaccination and month of that vaccination. More \ninformation: https://www.cdc.gov/covidvaxview/weekly -dashboard/child -coverage -vaccination.html  0%25%50%75%100%\nSep Oct Nov Dec Jan Feb Mar AprCOVID -19 vaccine coverage (%)\nMonth6 months-4 years, 2023-2024\n6 months-4 years, 2024-2025\n5-17 years, 2023-2024\n5-17 years, 2024-2025\n31COVID -19 Vaccination Coverage Among Adults ≥18 Years, 2023 -2024 and \n2024 -2025, NIS -ACM\nNational Immunization Survey -Adult COVID Module: Data from adults age ≥18 years are collected by telephone interview using a random -digit -dialed sample of cell telephone numbers  stratified by \nstate, the District of Columbia, five local jurisdictions (Bexar County TX, Chicago IL, Houston TX, New York City NY, and Phi ladelphia County PA), and Puerto Rico and the U.S. Virgin Islands. Data are \nweighted to represent the non -institutionalized U.S. population and mitigate possible bias that can result from an incomplete sa mple frame (exclusion of households with no phone service or only \nlandline telephones) or non -response. All responses are self -reported. For more information about the survey, see https://www.cd c.gov/nis/about/index.html.0%25%50%75%100%COVID -19 Vaccination Coverage (%)\nWeek2023-2024 COVID-19 Vaccination Coverage 2024-2025 COVID-19 Vaccination Coverage\nMedicare fee -for-service beneficiaries aged ≥65 years were more likely to receive a \n2024 -2025 COVID -19 vaccine dose if they had an underlying medical condition  \nFee-for-Service:  enrolled in Medicare Parts A/B (and not Part C) for 365 days prior to reporting period. Estimates are based on  data released by Medicare claims data through January 2025; data may be incomplete \nafter December 7, 2024, due to 6 -week reporting lag. Data on uptake by season, race, and ethnicity can be accessed at: https://www.cdc.gov/covidvaxview/weekly -dashboard/adults -65yrs -older -vaccination.html . \nData on uptake by underlying medical condition from internal, unpublished analyses.32%\n29%\n28%\n24%\n0%25%50%75%100%\n08/25/24 -\n09/07/2409/08/24 -\n09/21/2409/22/24 -\n10/05/2410/06/24 -\n10/19/2410/20/24 -\n11/02/2411/03/24 -\n11/16/2411/17/24 -\n11/30/2412/01/24 -\n12/14/2412/15/24 -\n12/28/2412/29/24 -\n01/11/2501/12/25 -\n01/25/25% with ≥1 2024 -2025 COVID -19 vaccine dose\nTwo -week periodWeekly cumulative COVID -19 vaccination coverage, by underlying medical condition status,\nMedicare fee -for-service beneficiaries aged ≥65 years, August 2024 -January 2025\nAny immunocompromising condition\nAny underling medical condition\nOverall\nNo underlying medical condition\nCumulative rates of COVID -19–associated hospitalizations for the \n2024 –2025 season are lower compared to 2023 -2024 season.\n33020406080100120\nJul Aug Sep Oct Nov Dec Jan Feb Mar Apr May JunHospitalizations per 100,000 population\nHospitalization monthCumulative Rates of COVID -19-Associated Hospitalizations among children and adolescents aged ≤17 years,\nby Surveillance Season* — COVID -NET, July 2023 –May 2025\n≤4 years, 2023 –2024 5–17 years, 2023 –2024\n≤4 years, 2024 –2025 5–17 years, 2024 –2025\n* Seasons are defined as July through June. The 2024 –2025 season shows data from July 2024 –April 2025 and is ongoing.\nData source: https://www.cdc.gov/resp -net/dashboard/  \nNote that rates are not adjusted for testing or limited to admissions where the respiratory infection is the likely primary r eason for admission. \nAccounting for correlated vaccination behaviors\n•Pivotal assumption (when estimating VE against ARI causing pathogens):  risk of alternative causes \nof ARI (e.g., influenza infection) is independent  of exposure status (i.e., COVID -19 vaccination) \n-If violated, VE estimates may be biased  \nDoll MK et al. 2022 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9129127/  34•Three key considerations\n-When is this assumption violated?\n• When controls are positive for other vaccine preventable \nillness (e.g., influenza) → due to the correlation between \nvaccination behaviors, influenza infection is not \nindependent of exposure (COVID -19 vaccination) \n-How might it impact VE estimates?\n• Over representation of unvaccinated controls and \nunderestimation of COVID -19 VE\n• Magnitude of bias depends on\n– Proportion of controls positive for alternative \nvaccine preventable ARI\n– Vaccination coverage\n– True VE \n-What can be done to mitigate? \n• Design: Exclude influenza positive controls\n• Analysis:  Adjust for influenza vaccinationVaccination \nMotivation\n(Unmeasured) Influenza\nVaccination\nCOVID -19\nVaccinationInfluenza\nInfection\nSARS -CoV -2\nInfection\nSARS -CoV -2 + SARS -CoV -2 -\nVaccinated a b\nUnvaccinated c dOR = a ÷ c / b ÷ d\nVE = (1 - OR) x 100% \nVE = vaccine effectiveness | ARI = acute respiratory infection\nAccounting for correlated vaccination behaviors\n•COVID -19 VE estimates are robust\n-Little variation in VE estimates, \nregardless of accounting for \ncorrelated vaccination behaviors\nCDC Unpublished Data; Payne AB et al. 2023 https://pmc.ncbi.nlm.nih.gov/articles/PMC11823735/  35Vaccination Status Model TotalAdjusted VE*, \n% (95% CI)\nNo 2023 -2024 dose\nA 33,935 Ref\nB 33,935 Ref\nC 20,355 Ref\nD 22,989 Ref\nE 30,810 Ref\n2023 -2024 dose, 7 -179 days\nA 9,182 46 (41 -50)\nB 9,182 49 (44 -54)\nC 6,179 49 (44 -53)\nD 6,963 47 (43 -52)\nE 8,314 47 (43 -52)\n2023 -2024 dose, 7 -59 days\nA 3,848 56 (50 -61)\nB 3,848 58 (52 -63)\nC 2,498 58 (52 -63)\nD 2,785 57 (51 -62)\nE 3,535 57 (51 -62)\n2023 -2024 dose, 60 -119 days\nA 4,375 38 (30 -45)\nB 4,375 41 (34 -48)\nC 3,007 41 (34 -48)\nD 3,442 39 (32 -46)\nE 3,897 39 (32 -46)\n2023 -2024 dose, 120 -179 days\nA 959 28 (5 -45)\nB 959 32 (11 -48)\nC 674 34 (13 -50)\nD 736 31 (9 -47)\nE 882 29 (8 -46)\n0 50 100\nAdjusted VE*Model Description\nA Ignore potential correlation\nB Control for influenza and RSV vaccination status in model\nC Limit to controls confirmed influenza - and RSV -negative\nD Limit controls to tested for SARS -CoV -2, influenza, and RSV\nE Limit to controls presumed influenza - and RSV -negative\nVE = Vaccine Effectiveness\n*VE against COVID -19-associated hospitalization among adults aged ≥60 years was calculated as\n(1-odds ratio) x 100%, estimated using a test -negative case -control design, adjusting for age, sex, \nrace and ethnicity, VISION site ID, and calendar time (days since July 1, 2023).  The reference group \nfor all models was no 23/24 vaccine recipe regardless of prior vaccination history.\nAbsolute VE of COVID -19 original  monovalent and bivalent doses received prior to  or during  \npregnancy against COVID -19–associated emergency department/urgent care encounters among \nimmuno competent  pregnant women aged 18 -45 years  — VISION\nJune 2022 – August 2023\nVaccine effectiveness was calculated by comparing the odds of COVID -19 vaccination in case -patients and control -patients using t he equation: (1 – adjusted odds ratio) x 100%. Odds ratios were estimated by \nmultivariable logistic regression. The odds ratio was adjusted for a ge, ethnicity, race, underlying medical conditions, gestational age at encounter, site, Medicaid status, day of encounter, site  facility \nurbanicity.\nPregnant women were classified as (1) unvaccinated (no COVID -19 vaccine doses) or (2) vaccinated with the last COVID -19 vaccine dose ≥7 days before the index date (including the original \nmonovalent and/or bivalent vaccines). The index date was defined as (1) the collection date of a respiratory specimen associa ted with the most recent positive or negative SARS -CoV-2 test result \nbefore the ED/UC encounter or (2) the encounter date, if testing occurred only after the encounter. COVID -19 vaccination dates a nd vaccine types were identified by electronic medical records. \nOriginal monovalent COVID -19 vaccines (11 December 2020 –31 August 2022) include Moderna, Pfizer -BioNTech, and Janssen (Johnson &  Johnson), and bivalent COVID -19 vaccines include Moderna \nand Pfizer -BioNTech. Bivalent vaccines (1 September 2022 –10 September 2023) contain components from the SARS -CoV-2 ancestral and  Omicron BA.4/BA.5 strains.\nCiesla et al., OFID 2024, https://academic.oup.com/ofid/article/11/9/ofae481/7743292  36Vaccine Dosage PatternTotal\ntestsSARS -CoV-2-\ntest-positive,\nN (%)Median interval\nsince last dose,\ndays (IQR)Adjusted VE\n(95% CI)\nAbsolute VE\nUnvaccinated (ref) 2991 403 (13) -- Ref\nMost recent monovalent or bivalent dose received:\n≥6 months before pregnancy 3014 365 (12) 483 (393,579) 6 (-11, 21)\n<6 months before pregnancy 1203 143 (12) 267 (204, 325) 28 (11, 42)\nDuring pregnancy 469 35 (7) 91 (45, 158) 52 (29, 67)\n-20 0 20 40 60 80 100\nVaccine Effectiveness (%)\n37Context for interpreting COVID -19 VE across age groups: high infection -\ninduced seroprevalence in children and adults\n* Data on persons aged 0 -17 years from nationwide commercial laboratory testing of residual serum specimens from ~27,000 childre n and adolescents originally submitted for routine screening or clinical management, \nhttps://covid.cdc.gov/covid -data -tracker/#pediatric -seroprevalence\n** Data on persons aged ≥16 years from a longitudinal, national cohort of ~35,000 blood donors, https://covid.cdc.gov/covid -data -tracker/#nationwide -blood -donor -seroprevalence -2022 89%\n92%\n87%\n76%16-29 years\n30-49 years\n50-64 years\n≥65 years\n0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%\nPercent with infection -induced immunityPercent of persons with infection -induced immunity, based on anti -nucleocapsid results from blood donors,\nadolescents and adults , October – December 2023**\nVE findings should be interpreted as the added benefit provided by COVID -19 vaccination in a \npopulation with a high prevalence infection -induced immunity.91%\n93%0-11 years\n12-17 yearsPercent of persons with infection -induced immunity, based on anti -nucleocapsid results from residual specimens from commercial l aboratories,\nchildren and adolescents , November – December 2022*Age at blood draw\n38Age group/2023 -2024 COVID -19 vaccination \nstatus/days since doseTotal\nencountersSARS -CoV -2-\ntest -positive,\nN (%)Median interval since\nlast dose among\nvaccinated, days (IQR) Adjusted VE (95% CI)\n≥18 years\nNo 2023 -2024 COVID -19 dose (ref) 279,733 31,167 (11) 756 (543 -920) ref\n2023 -2024 COVID -19 dose , 7-299 days earlier 65,906 5,929 (9) 117 (61 -189) 24 (21 to 26)\n2023 -2024 COVID -19 dose , 7-59 days earlier 16,082 1,228 (8) 34 (21 -47) 49 (45 to 52)\n2023 -2024 COVID -19 dose , 60-119 days earlier 17,653 1,521 (9) 88 (73 -103) 26 (22 to 30)\n2023 -2024 COVID -19 dose , 120 -179 days earlier 13,815 875 (6) 147 (133 -163) 18 (12 to 24)\n2023 -2024 COVID -19 dose , 180-299 days earlier 18,356 2,305 (13) 231 (204 -261) -7 (-13 to -2)\n18-64 years\nNo 2023 -2024 COVID -19 dose (ref) 200,443 21,053 (10) 789 (624 -934) ref\n2023 -2024 COVID -19 dose , 7-299 days earlier 23,655 1,893 (8) 116 (59 -187) 22 (18 to 26)\n2023 -2024 COVID -19 dose , 7-59 days earlier 5,952 360 (6) 34 (20 -47) 55 (49 to 59)\n2023 -2024 COVID -19 dose , 60-119 days earlier 6,285 436 (7) 88 (74 -104) 29 (22 to 36)\n2023 -2024 COVID -19 dose , 120 -179 days earlier 4,971 256 (5) 147 (133 -163) 22 (11 to 31)\n2023 -2024 COVID -19 dose , 180-299 days earlier 6,447 841 (13) 230 (203 -260) -24 ( -34 to -14)\n≥65 years\nNo 2023 -2024 COVID -19 dose (ref) 79,290 10,114 (13) 669 (436 -868) ref\n2023 -2024 COVID -19 dose , 7-299 days earlier 42,251 4,036 (10) 117 (62 -190) 25 (22 to 28)\n2023 -2024 COVID -19 dose , 7-59 days earlier 10,130 868 (9) 34 (21 -47) 46 (41 to 50)\n2023 -2024 COVID -19 dose , 60-119 days earlier 11,368 1,085 (10) 88 (73 -103) 25 (20 to 30)\n2023 -2024 COVID -19 dose , 120 -179 days earlier 8,844 619 (7) 148 (133 -163) 19 (11 to 26)\n2023 -2024 COVID -19 dose , 180-299 days earlier 11,909 1,464 (12) 232 (204 -262) 2 (-5 to 8)VISION: VE of 2023 -2024 COVID -19 vaccine against COVID -19-associated emergency \ndepartment/urgent care encounters among immunocompetent adults aged ≥18 years, by age group\nSeptember 2023 – August 2024\nLink-Gelles et al., JAMA Network Open. VE was calculated as (1 − odds ratio) x 100%, estimated using a test -negative case -control design, with the odds ratio adjusted for age, sex, race and ethnicity, geographic \nregion, and calendar time. A VE estimate less than zero is possible due to the waning protection from COVID -19 vaccines coupled with the existing infection -induced immunity in unvaccinated participants. As \nprotection from vaccination wanes, and unvaccinated people accumulate protection from repeated infections, this may yield neg ative VE. -40 -20 0 20 40 60 80 100\n39VISION: VE of 2023 -2024 COVID -19 vaccine against COVID -19-associated \nhospitalization among immunocompetent adults aged ≥18 years, by age group\nSeptember 2023 – August 2024\nAge group/2023 -2024 COVID -19 vaccination \nstatus/days since doseTotal\nencountersSARS -CoV -2-\ntest -positive,\nN (%)Median interval since\nlast dose among\nvaccinated, days (IQR) Adjusted VE (95% CI)\n≥18 years\nNo 2023 -2024 COVID -19 dose (ref) 87,718 8,480 (10) 733 (507 -918) ref\n2023 -2024 COVID -19 dose , 7-299 days earlier 24,213 1,900 (8) 123 (63 -193) 29 (25 to 33)\n2023 -2024 COVID -19 dose , 7-59 days earlier 5,618 417 (7) 34 (21 -47) 51 (46 to 56)\n2023 -2024 COVID -19 dose , 60-119 days earlier 6,231 486 (8) 88 (74 -104) 36 (30 to 42)\n2023 -2024 COVID -19 dose , 120 -179 days earlier 5,275 306 (6) 149 (134 -164) 22 (12 to 31)\n2023 -2024 COVID -19 dose , 180-299 days earlier 7,089 691 (10) 230 (203 -260) -4 (-14 to 5)\n18-64 years\nNo 2023 -2024 COVID -19 dose (ref) 35,303 2,229 (6) 788 (606 -940) ref\n2023 -2024 COVID -19 dose , 7-299 days earlier 4,249 234 (6) 120 (62 -188) 15 (2 to 27)\n2023 -2024 COVID -19 dose , 7-59 days earlier 1,005 60 (6) 33 (21 -46) 31 (10 to 47)\n2023 -2024 COVID -19 dose , 60-119 days earlier 1,113 52 (5) 89 (75 -104) 33 (11 to 50)\n2023 -2024 COVID -19 dose , 120 -179 days earlier 936 33 (4) 148 (135 -164) 21 ( -12 to 45)\n2023 -2024 COVID -19 dose , 180-299 days earlier 1,195 89 (7) 229 (201 -259) -31 ( -66 to -4)\n≥65 years\nNo 2023 -2024 COVID -19 dose (ref) 52,415 6,251 (12) 698 (467 -899) ref\n2023 -2024 COVID -19 dose , 7-299 days earlier 19,964 1,666 (8) 123 (63 -194) 31 (27 to 35)\n2023 -2024 COVID -19 dose , 7-59 days earlier 4,613 357 (8) 34 (21 -47) 54 (49 to 59)\n2023 -2024 COVID -19 dose , 60-119 days earlier 5,118 434 (8) 88 (73 -104) 36 (29 to 42)\n2023 -2024 COVID -19 dose , 120 -179 days earlier 4,339 273 (6) 149 (134 -164) 21 (10 to 31)\n2023 -2024 COVID -19 dose , 180-299 days earlier 5,894 602 (10) 230 (204 -261) 0 (-10 to 10)\n-80 -60 -40 -20 0 20 40 60 80 100Link-Gelles et al., JAMA Network Open. VE was calculated as (1 − odds ratio) x 100%, estimated using a test -negative case -control design, with the odds ratio adjusted for age, sex, race and ethnicity, geographic \nregion, and calendar time. A VE estimate less than zero is possible due to the waning protection from COVID -19 vaccines coupled with the existing infection -induced immunity in unvaccinated participants. As \nprotection from vaccination wanes, and unvaccinated people accumulate protection from repeated infections, this may yield neg ative VE. \n40Characteristics of emergency department and urgent care encounters and hospitalizations \namong adults aged ≥18 years with COVID -19-like illness, by COVID -19 case status and CDC \nvaccine effectiveness network — VISION and IVY Networks\nSeptember 2024 –May 2025 \nCharacteristicVaccine effectiveness network and setting, no. (column %)\nVISION\nED/UC encounters,\nall adults aged ≥18 yearsVISION\nhospitalizations,\nall adults aged ≥65 yearsIVY\nhospitalizations,\nall adults aged ≥65 years\nTotalCOVID -19\ncase -\npatientsCOVID -19\ncontrol -\npatients TotalCOVID -19\ncase -\npatientsCOVID -19\ncontrol -\npatients TotalCOVID -19\ncase -\npatientsCOVID -19\ncontrol -\npatients\nTotal 240,976 14,621 226,355 65,751 4,341 61,410 4,392​ 1,190​ 3,202\nMedian age 52 [34, 71] 57 [36, 74] 52 [34, 71] 78 [71, 84] 79 [73, 86] 78 [71, 84] 75 [70, 82]​ 77 [71, 84]​ 75 [69, 81]\nAge group\n18-64 years 158,028 (66) 8,688 (59) 149,340 (66) -- -- -- -- -- --\n≥65 years 82,948 (34) 5,933 (41) 77,015 (34) 65,751 (100) 4,341 (100) 61,410 (100) 4,392 (100) 1,190 (100)​ 3,202 (100)\nImmunocompromised* -- -- -- 15,350 (23)​ 883 (20)​ 14,467 (24)​ 1,137 (26)​ 258 (22)​ 879 (28)\nUpdated from Link -Gelles, et al. MMWR: https://www.cdc.gov/mmwr/volumes/74/wr/mm7406a1.htm\nED/UC = emergency department/urgent care; VISION data go through May 2025; IVY data go through April 2025\n* Immunocompromised status is not evaluated for ED/UC encounters due to a higher likelihood of incomplete discharge diagnosis  codes in this setting.\n41Effectiveness of 2024–2025 COVID -19 vaccination against COVID -19–associated emergency \ndepartment/urgent care  encounters by age group — VISION\nSeptember 2024 – May 2025\nUpdated from: Link -Gelles, et al. MMWR: https://www.cdc.gov/mmwr/volumes/74/wr/mm7406a1.htm . Vaccine effectiveness was calculated by comparing the odds of 2024 –2025 COVID -19 vaccination in case -patients and control -patients using the equation: (1 – adjusted odds \nratio) x 100%. Odds ratios were estimated by multivariable logistic regression. The odds ratio was adjusted for age, sex, rac e and ethnicity, calendar day, and geographic region. The “no 2024 –2025 dose” group included all eligible persons who did not recei ve a 2024 –2025 COVID -19 \nvaccine dose, regardless of number of previous COVID -19 vaccine doses (if any) received.  * Time since vaccination is for most r ecent dose, which could have been an original monovalent, bivalent, 2023 -2024, or 2024 -2025 COVID -19 vaccine.Age group/2024 -2025 COVID -19 vaccination \nstatus/days since doseCOVID -19\ncase -patients\nN (Col %)COVID -19\ncontrol -patients\nN (Col %)Median interval since\nlast dose among\nvaccinated*, days (IQR) Adjusted vaccine effectiveness % (95% CI)\n≥18 years\nNo 2024 -2025 COVID -19 dose  (Ref) 12,927 (88) 188,006 (83) 1,068 (742 -1,224) Ref\nReceived 2024 -2025 COVID -19 dose 7–179 days earlier 1,694 (12) 38,349 (17) 89 (50 -129) 34 (30 -37)\n2024 -2025 COVID -19 dose , 7–59 days earlier 572 (4) 11,763 (5) 34 (21 -47) 36 (30 -42)\n2024 -2025 COVID -19 dose , 60–119 days earlier 695 (5) 14,685 (6) 89 (74 -104) 35 (29 -40)\n2024 -2025 COVID -19 dose , 120 –179 days earlier 427 (3) 11,901 (5) 147 (133 -162) 28 (20 -35)\n18-64 years\nNo 2024 -2025 COVID -19 dose  (Ref) 8,212 (95) 136,067 (91) 1,105 (866 -1,245) Ref\nReceived 2024 -2025 COVID -19 dose 7–179 days earlier 476 (5) 13,273 (9) 86 (48 -127) 32 (25 -38)\n2024 -2025 COVID -19 dose , 7–59 days earlier 156 (2) 4,244 (3) 33 (20 -46) 39 (29 -49)\n2024 -2025 COVID -19 dose , 60–119 days earlier 199 (2) 5,155 (3) 89 (74 -104) 32 (21 -41)\n2024 -2025 COVID -19 dose , 120 –179 days earlier 121 (1) 3,874 (3) 147 (132 -163) 20 (4 -34)\n≥65 years\nNo 2024 -2025 COVID -19 dose  (Ref) 4,715 (79) 51,939 (67) 907 (448 -1,166) Ref\nReceived 2024 -2025 COVID -19 dose 7–179 days earlier 1,218 (21) 25,076 (33) 91 (51 -131) 35 (30 -39)\n2024 -2025 COVID -19 dose , 7–59 days earlier 416 (7) 7,519 (10) 34 (21 -47) 36 (29 -43)\n2024 -2025 COVID -19 dose , 60–119 days earlier 496 (8) 9,530 (12) 90 (75 -105) 36 (29 -42)\n2024 -2025 COVID -19 dose , 120 –179 days earlier 306 (5) 8,027 (10) 147 (133 -162) 30 (21 -39)\n0 20 40 60 80 100\nVaccine effectiveness (%)\nIVY: Number of COVID -19 case -patients by hospital admission week and \nSARS -CoV-2 lineage\nSeptember 1, 2024 –April 27, 2025 \nDates are for the start of the admission week. \n\n43IVY: Effectiveness of 2024–2025 COVID -19 vaccine against hospitalization \namong adults aged ≥18 years by SARS -CoV-2 lineage using viral whole -\ngenome sequencing\n•Population\n•Cases:  COVID -like illness (CLI) and test positive for SARS -CoV-2*;restricted to patients with sequence -\nconfirmed†KP.3.1.1 lineage (Nextstrain  clade 24E)  or XEC lineage (Nextstrain  clade 24F)\n•Controls: CLI and test negative forSARS -CoV-2, influenza viruses, and RSV (≥60 years) byRT-PCR\n•Analytic Period: September 1, 2024 –April 27, 2025\n•VE§ against hospitalization was calculated separately using case -patients with sequence -confirmed SARS -\nCoV-2 KP .3.1.1 and XEC lineage infections\n* Case patients who were co -infected with influenza viruses or RSV were excluded.\n† Identification of a SARS -CoV-2 lineage through viral whole -genome sequencing was successful for 49% of case -patients during the  analysis period.\n§ Vaccine effectiveness was calculated by comparing the odds of 2024 –2025 COVID -19 vaccination in case -patients and control -patie nts using the equation: (1 – adjusted odds ratio) x 100%. Odds ratios \nwere estimated by multivariable logistic regression.  The odds ratio was adjusted for age, sex, race and ethnicity, geographic region (U.S. Dep artment of Health and Human Services Region) and calendar \ntime (biweekly intervals).\nLineage and 2024 -2025 COVID -19 \nvaccination statusCOVID -19 case -patients COVID -19 control -patients\nVaccine Effectiveness§% (95% CI)  N (Col %)Median interval\nsince last dose \namong vaccinated,\ndays (IQR) N (Col %)Median interval \nsince last dose \namong vaccinated,\ndays (IQR)\nKP.3.1.1\nNo 2024 -2025 COVID -19 dose (Ref) 309 (91) Not available 5,202 (84) Not available Ref\nReceived 2024 -2025 COVID -19 dose 7–179 days earlier 29 (9) 56 (33 –75) 1,027 (16) 94 (57 –133) 45 (19 –64)\nXEC\nNo 2024 -2025 COVID -19 dose (Ref) 173 (84) Not available 5,202 (84) Not available Ref\nReceived 2024 -2025 COVID -19 dose 7–179 days earlier 32 (16) 87 (52 –112) 1,027 (16) 94 (57 –133) 34 (2 –57)\n* These results include both immunocompetent and immunocompromised persons.\n† KP.3.1.1 lineage was defined by Nextstrain  clade 24E and XEC lineage was defined by Nextstrain  clade 24F.\n§ Vaccine effectiveness was calculated by comparing the odds of 2024 –2025 COVID -19 vaccination in case -patients and control -patien ts using the equation: (1 – adjusted odds ratio) x 100%. Odds ratios were \nestimated by multivariable logistic regression.  The odds ratio was adjusted for age, sex, race and ethnicity, geographic region (U.S. Department of Health and Human Services Re gion) and calendar time \n(biweekly intervals).-20 0 20 40 60 80 100Vaccine  Effectiveness (%)IVY: Effectiveness of 2024–2025 COVID -19 vaccine against hospitalization \namong adults aged ≥18 years* by SARS -CoV-2 lineage †\nSeptember 1, 2024 – April 27, 2025\n45*Data sources included Medicare Enrollment Database (EDB) and Common Medicare Environment (CME), Common Working File (CWF) an d Shared System Data (SSD) Medicare Parts A/B claims data, Minimum Data Set (MDS), and CDC/ATSDR Social \nVulnerability Index (SVI)\n**Hazard ratios adjusted for age group, sex, race, long/short nursing home stay status, social vulnerability index, state, ru ral/urban classification, number of underlying medical conditions, 2022 -2023 influenza vaccination status, and bivalent\nCOVID -19 vaccination status.Medicare data\n• Design: Retrospective cohort\n• Data source:  Medicare fee -for-service claims data*\n• Population:  Persons aged ≥65, recent nursing home \nstay \n• Censoring events: ​\n– COVID -19-associated thromboembolic event​ (TE)\n– Death​\n– Disenrollment in Medicare Parts A/B​\n– Enrollment in Medicare Part C​\n– Admission to hospice facility​\n– Dialysis encounter\n– Receipt of a 2023 -2024 COVID -19 vaccine dose <60 days from \nbivalent COVID -19 vaccine dose\n– Receipt of a second 2023 -2024 COVID -19 vaccine dose <120 days \nfrom first 2023 -2024 COVID -19 vaccine dose\n– Receipt of a third 2023 -2024 COVID -19 vaccine dose\n– End of study period\n• VE = (1 - adjusted hazard ratio**) x 100%\nwhere adjusted hazard ratio = 𝑟𝑎𝑡𝑒  𝑜𝑓 𝐶𝑂𝑉𝐼𝐷 −19−𝑎𝑠𝑠𝑜𝑐𝑖𝑎𝑡𝑒𝑑  𝑇𝐸𝑣𝑎𝑐𝑐𝑖𝑛𝑎𝑡𝑒𝑑\n𝑟𝑎𝑡𝑒  𝑜𝑓 𝐶𝑂𝑉𝐼𝐷 −19−𝑎𝑠𝑠𝑜𝑐𝑖𝑎𝑡𝑒𝑑  𝑇𝐸𝑢𝑛𝑣𝑎𝑐𝑐𝑖𝑛𝑎𝑡𝑒𝑑\nCOVID -19 TEOther Censoring Event\nUnvaccinated person -time\nVaccinated person -time\nStart Follow -up End Study Period\n46Age group/2023 -2024 COVID -19 vaccination \nstatus/days since doseNumber of \nBeneficiarie\nsNumber of \nOutcomesMedian Follow -up Time \nContributed to Category \n(Days) Adjusted VE (95% CI)\n≥65+ years\nNo 2023 -2024 COVID -19 dose (ref) 516,176 4,335 142 Ref\n2023 -2024 COVID -19 dose , ≥ 7 days earlier 209,228 726 161 31% (25%, 36%)\n2023 -2024 COVID -19 dose , 7-59 days earlier 26,646 198 53 50% (42%, 56%)\n2023 -2024 COVID -19 dose , 60-119 days earlier 37,426 238 60 29% (20%, 38%)\n2023 -2024 COVID -19 dose , 120 -179 days earlier 23,558 138 60 15% (0%, 28%)\n2023 -2024 COVID -19 dose , ≥ 180  days earlier 121,598 152 65 0% ( -17%, 14%)\n65-74 years\nNo 2023 -2024 COVID -19 dose (ref) 116,278 1,025 176 Ref\n2023 -2024 COVID -19 dose , ≥ 7 days earlier 40,719 132 178 29% (16%, 39%)\n2023 -2024 COVID -19 dose , 7-59 days earlier 5,029 34 53 47% (36%, 57%)\n2023 -2024 COVID -19 dose , 60-119 days earlier 6,646 55 60 26% (11%, 39%)\n2023 -2024 COVID -19 dose , 120 -179 days earlier 4,984 22 60 12% ( -9%, 29%)\n2023 -2024 COVID -19 dose , ≥ 180  days earlier 24,060 21 64 -5% ( -29%, 15%)\n≥75+ years\nNo 2023 -2024 COVID -19 dose (ref) 399,898 3,310 135 Ref\n2023 -2024 COVID -19 dose , ≥ 7 days earlier 168,509 594 157 31% (25%, 37%)\n2023 -2024 COVID -19 dose , 7-59 days earlier 21,617 164 53 50% (42%, 57%)\n2023 -2024 COVID -19 dose , 60-119 days earlier 30,780 183 60 30% (20%, 39%)\n2023 -2024 COVID -19 dose , 120 -179 days earlier 18,574 116 60 16% (1%, 29%)\n2023 -2024 COVID -19 dose , ≥ 180  days earlier 97,538 131 65 1% ( -17%, 16%)VE of 2023 -2024 COVID -19 vaccine against COVID -19 related thromboembolic events among immunocompetent  \nMedicare fee -for-service beneficiaries residing in a nursing home, by age group and time since vaccination\nSeptember 2023 – July 2024\n-40 -20 0 20 40 60 80 100\nCDC, unpublished data\nModels are adjusted for age group, sex, race, long/short NH stay status, social vulnerability index (SVI), state, rural/urban classification, number of UMC categories, 2022 -2023 influenza vaccination status, and bivalent COVID -19 vaccination status.  \nInfection -induced SARS -CoV-2 seroprevalence among U.S. \nchildren — September 2021 – December 2022\n47\nInfection -induced (nucleocapsid \nantibody) seroprevalence\nMonth and Year\nShaded ranges depict 95% confidence intervals for the estimated seroprevalence shown by the dark line in the corresponding co lor. \nSource: https://covid.cdc.gov/covid -data -tracker/#pediatric -seroprevalence   \nAccessed: March 20, 20256-11 months\nPopulation SARS -CoV -2 spike antibody over time by the cumulative \nnumber of combined infections and vaccinations - U.S. blood donors \nages ≥16 years, September 2021 -December 2023\nSolid lines represent mean anti -spike IgG levels; dotted lines represent model based 25th-75th% percentiles\nHigher number of cumulative SARS -CoV-2 infections and COVID -19 vaccinations leads to higher antibody \nlevels, but with smaller incremental increases in antibodies with each exposure\nSpike IgG BAU/mL\nSource: https://covid.cdc.gov/covid -data -tracker/#nationwide -blood -donor -seroprevalence -2022 , CDC unpublished data 9\n491. Yousaf AR, Mak J, Gwynn L, et al. COVID -19 Vaccination and Odds of Post –COVID -19 Condition Symptoms in Children Aged 5 to 17 Years. JAMA Netw Open. 2025;8(2):e2459672.\n2. Mak J, Khan S, Britton A et al. Association of Messenger RNA Coronavirus Disease 2019 (COVID -19) Vaccination and Reductions i n Post COVID Conditions Following Severe Acute Respiratory Syndrome \nCoronavirus 2 Infection in a US Prospective Cohort of Essential Workers, The Journal of Infectious Diseases, Volume 231, Issu e 3, 15 March 2025, Pages 665 –676COVID -19 mRNA vaccination associated with reduced occurrence \nof Long COVID following COVID -19: June 2021 -September 2022\nAmong children aged 5 – 17 years:\nCompletion of the primary vaccine \nseries prior to infection associated \nwith reduced likelihood of Long \nCOVID symptoms1\n•57% for 1 or more symptoms\n•73% for 2 or more symptoms\n•72% for respiratory symptomsAmong adults: \n3 doses of original monovalent vaccine \nprior to infection associated with \nreduced likelihood of Long COVID \nsymptoms2\n•63% for gastrointestinal symptoms\n•44% for neurological symptoms \n•52% for other non -specific \nsymptoms \n•Data that explicitly quantifies vaccine effectiveness against transmission is ideal, \nbut it is often not feasible. \n•Other data can help us understand the impact of COVID -19 vaccination on \ntransmission, vaccine effectiveness against infection and infectiousness\n-COVID -19 vaccines provide moderate protection against infection in older children and adults.1,2,3 \n-COVID -19 vaccines may provide less protection against infection in young, infection -naïve \nchildren.4\n-COVID -19 vaccines moderately reduce infectiousness in individuals after they are infected with \nSARS -CoV-2 (see next slides).5\n•Preventing infections further reduces transmission by stopping future transmission \nchains. COVID -19 vaccine impact on transmission\n1 Feldstein L, et al. Effectiveness of mRNA COVID -19 Vaccines and Hybrid Immunity in Preventing SARS -CoV-2 Infection and Symptomatic COVID -19 Among Ad ults in the United States. \nhttps://academic.oup.com/jid/article/231/4/e743/7945315  \n2 Feldstein L , et al. Effectiveness of Bivalent mRNA COVID -19 Vaccines in Preventing SARS -CoV-2 Infection in Children and Adolescents Aged 5 to 17 Yea rs. https://jamanetwork.com/journals/jama/fullarticle/2814536  \n3 Kirwan PD, et al. Protection of vaccine boosters and prior infection against mild/asymptomatic and moderate COVID -19 infection in the UK SIREN hea lthcare worker cohort: October 2023 to March 2024. \nhttps://www.sciencedirect.com/science/article/pii/S0163445324002275?via%3Dihub  \n4 Feldstein L , et al. Protection From COVID -19 Vaccination and Prior SARS -CoV-2 Infection Among Children Aged 6 Months –4 Years, United States, Septemb er 2022 –April 2023 \nhttps://academic.oup.com/jpids/article/14/1/piae121/7917119  \n5 CDC. Respiratory Illness: Gauge of Household Transmission (RIGHT) Study​, unpublished with manuscript in progress.\n51COVID -19 Vaccine Effectiveness against SARS -CoV-2 (SCV2) Infectiousness\nRespiratory Illness: Gauge of Household Transmission (RIGHT) Study\nProspective h ousehold transmission study of SARS -CoV-2, January 2024 –January 2025\nPreliminary analysis (unpublished, manuscript in progress) from RIGHT Study shared by research teams at CDC, Vanderbilt Unive rsity Medical Center, University of Washington, and Columbia \nUniversity Irvin Medical Center.\nIndividuals with SARS -CoV-2 infection who had received a COVID -19 \nvaccination within prior 6 months had lower risk of transmitting to other \nhousehold contacts. Vaccine effectiveness at reducing transmission to others \nwas 45%.\nPreliminary analysis (unpublished, manuscript is progress) from RIGHT Study Jan 2024 -Jan 2025 shared by research teams at CDC, V anderbilt University Medical Center, University of Washington, and \nColumbia University Irvin Medical Center. *Adjusted for age of contact, COVID -19 vaccination status of contact, age of primary case, enrollment state, number of people in  the \nhome, enrollment timing, and clustering by household\n† Vaccine effectiveness against infectionAdjusted* Risk of SARS -CoV-2 Infection in Household Contact by Primary Case Vaccination Status\n†", "summary": "Updates to COVID -19 Vaccine Effectiveness Advisory Committee on Immunization Practices September 19, 2025National Center for Immunization and Respiratory Diseases   2•Vaccine effectiveness methods •Estimates of COVID -19 Vaccine Effectiveness in Children •Estimates of Maternal COVID -19 Vaccine Effectiveness •Estimates of COVID -19 Vaccine Effectiveness in Adults •ConclusionsAgenda –COVID -19 vaccine effectiveness (VE) Vaccine effectiveness methods 3 Randomized clinical trials vs. real -world…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-september-18-19-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-09-18-19/04-Srinivasan-covid-508.pdf", "doc_date": "2025-09-18", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 52}
{"title": "05 su covid 508", "content": "Vaccine safety signal detection and evaluation \nJohn Su\nImmunization Safety Office\nAdvisory Committee on Immunization Practices meeting\nSeptember 19, 2025\n\nOutline\n•Definitions\n•Approach to signal detection and evaluation\n•Example\n-Previous statistical signals for ischemic stroke in the Vaccine Safety Datalink (VSD)\nDefinition:  adverse event following immunization (AEFI)\n•Any untoward medical occurrence which follows immunization and which \ndoes not necessarily have a causal relationship with the usage of the \nvaccine. The adverse event may be any unfavorable or unintended sign, \nabnormal laboratory finding, symptom, or disease.\nNotes: “Immunization” as used in these definitions means the usage of a vaccine for the purpose of immunizing individuals. “Usage” i ncludes all processes that occur after a vaccine \nproduct has left the manufacturing/packaging site, i.e. handling, prescribing and administration of the vaccine.\nSource: Council for International Organizations of Medical Sciences. Definition and application of terms for vaccine pharmacovigilance: report of CIOMS/WHO Working Group on Vaccine \nPharmacovigilance. Geneva: CIOMS, 2012. \nDefinition:  signal\n•Information that arises from one or multiple sources (including \nobservations and experiments) which suggests a new potentially causal \nassociation, or a new aspect of a known association, between an \nintervention and an event or set of related events, either adverse or \nbeneficial, that is judged to be of sufficient likelihood to justify \nverificatory action.\nSource: Council for International Organizations of Medical Sciences. Definition and application of terms for vaccine pharmacovigilance: report of CIOMS/WHO Working Group on Vaccine \nPharmacovigilance. Geneva: CIOMS, 2012\nVaccine safety signal pathway \n*Adapted from: Practical Aspects of Signal Detection in Pharmacovigilance: Report of CIOMS Working Group VIII –CIOMS . (2010)Signal detection\n(and assessment )\nSignal Verified Signal Ruled OutHypothesis testing study for adverse event \nrisk after vaccine\nEvaluate biologic mechanisms and prevention strategiesCommunication and education, \nregulatory or public health action, \npossible further studies\nCDC’s Immunization Safety Office Monitors Vaccine Safety \nThrough Strong, Complementary Systems\nVAERS VSD CISA Project V-safe\nSystems work together to rapidly detect and assess potential \nsafety concerns to help inform public health actions 1990 1990 2001 2020\n\nEvaluation following previous statistical signals for \nischemic stroke in the Vaccine Safety Datalink (VSD)\nVSD •13 integrated healthcare organizations, covering >15.5 \nmillion people per year\n•Active monitoring using electronic medical records (EMR) \nand chart reviews\n•Rapid monitoring for pre -specified events as well as \nmonitoring for unexpected events\n•Can detect and assess safety signals\n•Develops innovative methods for monitoring safetyVaccine Safety Datalink (VSD)\nCollaborative Model for High -Quality Vaccine Safety Data\n\n•Links vaccination data to health outcomes Vaccine Safety Datalink (VSD)\nVaccination recordsHealth care visits\n•Hospital\n•Emergency dept.\n•ClinicPatient characteristics\nLinked by study IDs\nData are linked and kept at each site, not at CDC \n•Weekly sequential monitoring as data accrue\n•Monitors a limited set of prespecified adverse events of special interest\n-Potential cases identified using ICD -10 codes for healthcare encounters\n•Designed to detect statistical signals \n-A statistical signal is a finding from an analysis where a calculated value (i.e., the \ntest statistic) exceeds a specified statistical threshold \n-A statistical signal does not necessarily represent a vaccine safety problem and requires further assessment before conclusions can be drawn.\n•Since 2020, VSD has utilized a vaccinated concurrent comparator methodVaccine Safety Datalink (VSD)\nRapid Cycle Analysis (RCA) surveillance\nVaccinated Concurrent Comparator Method\nCOVID -19 vaccinated \nOct 30th \nCOVID -19vaccinated\nSept  20th Nov 3rd\n1 21\n43 63On each calendar day that an outcome \noccurs in a vaccinee (e.g., Nov 3rd), we \ncompare vaccinees in their risk interval (1 -\n21 days) with similar vaccinees in their \ncomparison interval (e.g., 43 -63 days). \n‘Similar’ means that people were in the \nsame age group, sex, race/ethnicity, and \nVSD site. \nInherently adjusts for calendar time.Risk interval 1 -21 days post -vaccination\nComparison interval 43 -63 days post -vaccination\nRef: Klein N, et al. Kaiser Permanente Northern California – \nhttps://jamanetwork.com/journals/jama/fullarticle/2784015Nov 3rd\nVaccine Safety Datalink (VSD) \nStatistical signal detection and evaluation\n•Statistical signal detection:  RCA concurrent comparator analysis \n-Intended to be rapid\n-Might have residual bias\n•Statistical signal evaluation:  self -controlled case -series (SCCS) analysis\n-Requires waiting for complete accrual of follow -up time\n-Less prone to bias \nCore list of adverse events of special interest monitored by U.S. federal agencies, 2020 -2023\n, \nhttps://www.sciencedirect.com/science/article/pii/S0264410X2400224X?via%3Dihub\n\nHistory of VSD RCA statistical signals for ischemic \nstroke following mRNA COVID -19 vaccines\nmRNA vaccine formulaVSD RCA \nstatistical signal for \nischemic stroke\n2020 -21original, primary series No\n2021- 22original,  booster dose No\n2022- 23b ivalent (original and BA.4/BA.5) Yes\n2023- 24XBB.1.5 Yes\n2024- 25KP. 2 No\nVSD RCA ischemic stroke after Pfizer -BioNTech bivalent booster, \nage ≥65 years, counts and adjusted rate ratios, \nOct 16, 2022– April 8, 2023\nThis information was previously presented to the Advisory Committee on Immunization Practices (ACIP) meeting on April 19, 202 3\nRR= 1.26 (95% CI 0.99– 1.60)\nRed dot represents sequential signal: p- value <0.01 (1- sided)\nInitial VSD statistical signal for ischemic stroke\nJanuary 13, 2023\nMay 31, 2023 update\n•“Other safety monitoring systems have not observed similar findings.”\n•“As time has passed and more safety data have accumulated, the initial \nfinding has decreased, and scientists believe factors other than vaccination might have contributed to the initial finding.”\n•“The current evidence does not support the existence of a safety issue.” \nCDC and FDA Identify Preliminary COVID -19 Vaccine Safety Signal for Persons Aged 65 Years and Older | FDA\n\nHistory of VSD RCA statistical signals for ischemic \nstroke following mRNA COVID -19 vaccines\n•2022- 2023 (bivalent vaccine)\n-Pfizer COVID -19 vaccine, age ≥65 years\n•Question about effect of same day administration with influenza vaccine\n•2023- 2024 (XBB.1.5 vaccine)\n-Moderna COVID -19 vaccine, age ≥65 years \n-Pfizer COVID -19 vaccine, age 50 -64 years \n•Additional information that was previously pending\n-A follow -up VSD analysis  using self- controlled case -series ( SCCS) analysis\n-FDA’s 2023- 2024 COVID -19 vaccine safety surveillance using Medicare claims \ndatabase results \nVSD SCCS analysis of ischemic stroke after Pfizer COVID -19 \nvaccine with or without influenza vaccine, 2022- 2023\nNo statistically significant increased risks found for either separate or \nsame day administrationIRR (95% Confidence Interval)\n21-d ay risk interval 42-d ay risk interval\nA ge groupCO VID -19 \nvaccination \nwithout \ninfluenza \nvaccinationSam e -day \ncoad ministration \no f CO VID -19 and \ninfluenza \nvaccinationsCO VID -19 \nvaccination \nwithout \ninfluenza \nvaccinationSam e -day \ncoad ministration \no f CO VID -19 and \ninfluenza \nvaccinations\nPfizerOverall 0.87 (0.58–1.29) 1.14 (0.88–1.47) 0.83 (0.58–1.19) 1.12 (0.91–1.37)\n12 - 64 years 0.92 (0.45–1.90) 0.88 (0.50–1.54) 0.93 (0.51–1.70) 1.06 (0.71–1.60)\n65+ years 0.85 (0.53–1.37) 1.25 (0.94–1.68) 0.79 (0.51–1.23) 1.15 (0.91–1.45)\nVSD SCCS analysis of ischemic stroke after mRNA COVID -19 \nvaccine with or without influenza vaccine, 2023- 2024\nNo statistically significant increased risks found for either separate or \nsame day administrationIRR (95% Confidence Interval)\n21-d ay risk interval 42-d ay risk interval\nA ge groupCO VID -19 \nvaccination \nwithout \ninfluenza \nvaccinationSam e -day \ncoad ministration \no f CO VID -19 and \ninfluenza \nvaccinationsCO VID -19 \nvaccination \nwithout \ninfluenza \nvaccinationSam e -day \ncoad ministration \no f CO VID -19 and \ninfluenza \nvaccinations\nPfizerOverall 1.19 (0.65- 2.17) 0.90 (0.64- 1.28) 1.12 (0.67- 1.89) 1.08 (0.79- 1.46)\n12 - 64 years 0.60 (0.08- 4.64) 1.17 (0.62- 2.21) 0.89 (0.24- 3.41) 1.23 (0.69- 2.17)\n65+ years 1.34 (0.71- 2.53) 0.83 (0.55- 1.26) 1.20 (0.68- 2.11) 1.06 (0.73- 1.53)\nModernaOverall 2.11 (0.81- 5.53) 1.41 (0.35- 5.76) 1.29 (0.48- 3.46) 1.13 (0.33- 3.93)\n12 - 64 years 2.73 (0.51- 14.52) 0.70 (0.05- 10.67) 1.53 (0.30- 7.80) 0.39 (0.01- 10.17)\n65+ years 1.94 (0.60- 6.30) 1.96 (0.43- 9.03) 1.22 (0.36- 4.16) 1.56 (0.46- 5.24)\nFDA surveillance:  Safety Monitoring of Multiple Health Outcomes Following \n2023– 2024 COVID -19 Vaccination among Medicare Beneficiaries Aged 65 \nYears and Older in the United States\n•Methods:  \n-Medicare Fee- for-Service (FFS) claims database from September 2023 to April 2024\n-Self-controlled case series design \n•Results: \n-Approximately 7.6 million Medicare FFS beneficiaries received a 2023 –2024 COVID -19 vaccination\n-Non -hemorrhagic stroke or transient ischemic attack\n•Pfizer:   IRR: 1.03 [99% CI: 0.91, 1.17]\n•Moderna:  IRR: 0.96 [99% CI: 0.85, 1.10]\n•Novavax:   IRR: 0.98 [99% CI: 0.19, 5.13]\n•Interpretation:  “we did not find evidence for an elevation in non- hemorrhagic stroke risk \nfollowing vaccination with any of the vaccine brands”\nhttps://www.medrxiv.org/content/10.1101/2025.01.03.25319975v1\nSummary\n•The Vaccine Safety Datalink (VSD) rapid cycle analysis (RCA) surveillance \nmonitored a list of pre -specified adverse events of special interest after \nCOVID -19 vaccines, including ischemic stroke\n•The VSD detected statistical signals for ischemic stroke during 2022- 2023 \nand 2023- 2024\n•Signal evaluation using self -controlled case- series analyses in the VSD and \nin other data sources have not confirmed an increased risk of ischemic stroke\nFor more information, contact CDC\n1-800- CDC- INFO (232 -4636)\nTTY:  1 -888- 232- 6348    cdc.gov\nFollow us on X (Twitter) @CDCgov & @CDCEnvironment\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position \nof the U. S. Centers for Disease Control and Prevention.", "summary": "Vaccine safety signal detection and evaluation  John Su Immunization Safety Office Advisory Committee on Immunization Practices meeting September 19, 2025  Outline •Definitions •Approach to signal detection and evaluation •Example -Previous statistical signals for ischemic stroke in the Vaccine Safety Datalink (VSD) Definition:  adverse event following immunization (AEFI) •Any untoward medical occurrence which follows immunization and which  does not necessarily have a causal relationship with…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-september-18-19-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-09-18-19/05-su-covid-508.pdf", "doc_date": "2025-09-18", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 22}
{"title": "06 el deiry kuperwasser covid 508", "content": "Wafik El-Deiry , MD, PhD, FACP\nDirector, Legorreta Cancer Center\nAssociate Dean, Oncologic SciencesWarren Alpert Medical School, BrownUniversity\nSeptember 19, 2025\nWorkgroup Safety Uncertainties of mRNA \nCOVID Vaccines\nCharlotte Kuperwasser, PhD\nDirector, Tufts Convergence Laboratory of \nBiomedical, Physical, and Engineering SciencesProfessor Developmental, Molecular & Chemical Biology, Tufts University School of Medicine\n\nTERMS OF REFERENCE # 6, 7 & 8\n1.Immune Changes  \n2.Biodistribution\n3.Frameshifting\n4.ImpuritiesSummary of Workgroup Activities for \nTORs\n\nImmune Changes\nCOVID vaccination, especially multiple doses, can lead to the \nfollowing immune responses: \n•IgG4 class switching 1\n•Production of anti -idiotype antibodies 2,3\n•Low long- term IgG Fc galactosylation and sialylation levels 4\n•Persistent cytokine changes5,6\n1)Irrgang et al. Sci Immunol (2023)\n2) Murphy et al . N Engl J Med (2022).\n3)Bellucci et al. Front Immunol. 2024 \n4)Buhre , et al. Front Immunol (2023) \n5)Alghamdi  et al. Immun Inflamm Dis ( 2025)\n6)Cabău et al. Vaccines (2024)\n7) Bhattacharjee et al. & Iwasaki A medRxiv (2025)\n8) Noé, A. et al. Front Immunol (2023).\n9)Yamamoto, M. et al. J Cut Immun and Allergy (2022)\n10)Park, H et al. Science Trans Med (2025).\n•Reduction in circulating memory and effector CD4 T \ncells, and increases in TNFα+ CD8 T cells 7\n•Risk of more persistent and/or recurring infections 8-10\nImmune Summary\n•The persistence, clinical significance, and potential long- term \nconsequences of these immune changes is uncertain.  \n•More research is needed to understand vaccine non- specific \neffects on innate and adaptive immunity and its ability to \nreprogram innate and adaptive immune cells. Covid vaccine safety issues\n\nPfizer -Comirnaty\nHigh levels detected in:\n-Injection site\n-LiverFDA Summary Basis for \nRegulatory Action (SBRA)\nUsed a luciferase reporter mRNA (instead of spike mRNA) in mice and rats, delivered in the same lipid \nnanoparticles (LNPs). Also tested biodistribution/metabolism of Pfizer’s two novel lipids (ALC -0315 and ALC-\n0159):\nIM injection in mice:Biodistribution\n\nBiodistribution\nModerna- SPIKEVAX\nHigh levels in:\n-Draining lymph nodes\n-Spleen\n-Eye\n-Liver\n•Low levels detected in many tissues including:\n-Heart, lung, testis, brain\n•In brain, ~2– 4% of plasma levels (so trace crossing of the blood– brain barrier).FDA Summary Basis for \nRegulatory Action (SBRA)\nStates no biodistribution study was performed with mRNA -1273; instead, FDA reviewed a biodistribution \nstudy of a different mRNA vaccine made with the same SM -102 LNP, considered those results supportive for \nSpikevax. \n\nBiodistribution\nVaccine \nmRNA in humansSitePersistence After \nVaccination Reference(s)\nAxillary lymph node Up to 30 days Krauson et al. NPJ Vaccines (2023)\nHeart\n(myocardium/cardiac ventricles)Up to 30 days1.Yonker et al., Circulation (2023) \n2.Boros et al, Pharmacol Res Perspect \n(2024) \n3.Krauson et al. NPJ Vaccines (2023)\nBlood ~15 days to 23 months1.Patterson et al, Hum Vaccin\nImmunother (2025)\n2.Ogata et al, Clin Infect Dis (2022)\n3.Fertig et al, Biomedicines (2022)\n4.Bhattacharjee et al. medRxiv (2025)\n5.Brogna et al. Proteomics Clin Appl \n(2023) \nCNS \n(skull/meninges/ Cerebral arteriesUp to ~17 months1.Ota et al. J Clin Neurosci (2025)\n2.Luis et al Brain Behav Immun Health \n(2021)\nBreast milk 45 hours Hanna et al. JAMA Pediatr (2022)\n\nBiodistribution Summary\n•Neither Moderna or Pfizer biodistribution studies used \ncommercial product for testing. \n•Neither Moderna or Pfizer biodistribution data showed confinement to site of injection. Distribution included draining \nlymph nodes, liver, spleen, heart, brain, lungs, and blood. It was noted that it could cross the BBB.\n•Covid vaccine mRNA has been detected in multiple tissues in humans including lymph nodes, heart, CNS, blood, and \nothers. \n•Covid vaccine mRNA has been reported to persist for up to 706 days.Covid vaccine safety issues\n\nFrameshifting\nOff-target protein production\n1) Mulroney, T. E.. Nature 625, 189- 194 (2024). \n2) Boros, L. G. et al. . Pharmacol Res Perspect (2024). •Therapeutic/in vitro- transcribed (IVT) mRNAs often contain \nmodified nucleotides (ribonucleotides), such as N¹-\nmethylpseudouridine to help reduce innate immune activation \nand increase stability.\n•Nucleoside- modified mRNA is synthetic and not a natural \nmRNA.\n•This modification instructs cells to produce off -target proteins \ndue to ribosomal slipping 1,2. \nCovid vaccine safety issues\n•There is evidence that these unintended/off -target proteins \ngenerate an immune (T cell) response in humans 1\n•Immunogenic or toxic properties of the non- spike proteins is \nunknown. \n•The health consequences of prolonged and persistent non-\nspike protein production have not been studied Frameshifting\n1) Mulroney, T. E.. Nature 625, 189- 194 (2024). \n\nImpurities\nSources during manufacturing\n1. Incomplete Digestion (DNAse )\n2. Separation Challenges\n1.Speicher, D. J., et al .(2025). \n2.McKernan, K. (2023).\n3.Raoult, D. (2024).\n4.Kaiser, S., et al (2025). \n5.Kämmerer , et al (2024). \n6.Buckhaults , P. (2023).\n7.König, B. (2024). \n8.Wang et al (2024). DNA impurities in vaccines have \nbeen reported in the following:\nSV40 promoter -\nenhancer ‐oriUnexpected impurities\nPfizer \nModerna\nDifferences between Pfizer vs Moderna \nPfizer/Comirnaty Moderna/Spikevax\nVector used for generating the \nDNA templateBacterial plasmid that contains \nmammalian -cell expression \nelements, including SV40 \npromoter/enhancer sequences.Bacterial plasmid\nForeign DNA material of \nconcernSV40 promoter/enhancer -oriFull nucleotide sequences have not \nbeen published\nDNA fragment sizes & \nquantityMean ~214 bp, maximum ~3.5 kb\n~ 371-1,548 ng per dose* Similar fragmented distribution, \nbut maximum size smaller, consistent with smaller plasmid \nbackbone. \n~ 1,130 -6,280 ng per \ndose* \nClinical trial vs marketed \nproductClinical trials used a clean PCR \nproduct template. Commercial product uses plasmid. No clinical trial was conducted on \nmarketed product . Same product on market as clinical \ntrial\n*FDA limit of \n10 ng set for naked DNA, not DNA in presence of LNP that carries DNA into cells and their nuclei.\nCovid vaccine safety issues\n•Pfizer vaccine: Exceeds limits1by ~36- 153-fold and SV40 \npromoter/enhancer sequences detected2. \n•Moderna: Exceeds limits1by ~112- 627-fold and small sizes could \nenable more integration events2.\n•No safety considerations or guidelines for LNP enveloped DNA \nimpurities have been established by regulatory agencies.\n•Concerns due to known DNA integration and gene \nactivation/disruption by SV40 promoter/enhancer sequences.Impurities\n1) Regulatory limit guidelines (WHO/FDA/ EMA)\n2) Speicher, D. J. et al. Autoimmunity (2025) \n\n•Cancers have been reported in mRNA vaccinated individuals in \ntemporal association to immunization including (38 case reports and \nstudy of 96 cases of PDAC outcomes vs IgG4):\n•High grade sarcoma at injection site (case report).\n•Kaposi’s sarcoma (cutaneous and conjunctival reported; 2 cases).\n•Non- Hodgkin’s Lymphoma (8 cases reported in one publication).\n•Primary Cutaneous Lymphomas (14 cases).\n•Marginal Zone B -cell Lymphoma (case report).\n•Glioblastoma (2 case reports).\n•Gastric and intestinal polyposis (2 case reports).\n•IgG4 correlates with poor survival outcomes in PDAC (96 cases).\n•Axillary Lymphangioma (case report).\n•Multiple Keratoacanthomas (skin cancer; case report).\n•Ph+ B -cell ALL (leukemia; case report).\n•T-cell ALL (leukemia; case report).\n•CMML (leukemia; case report).\n•Multiple Myeloma relapse (case report).\n•Cardiac Myxoma (2 case reports).COVID Vaccine Safety Issues: Impurities\n\nCOVID Vaccine Safety Issues: Impurities\nGaps in Knowledge\n•Extent of DNA contamination in current \nlots; plasmid biodistribution. \n•Genomic integration in tissues or tumors \nin vaccinated patients; mechanisms.\n•Prevalence of adverse outcomes from \nimpurities versus extent of contamination.•Multiple vaccinations and Spike persistence.\n•Cancer mechanisms. \n•Variations in host susceptibilities to \nadverse outcomes.\nCOVID- 19 vaccine safety concerns stem from unexpected \nbiological activities of mRNA gene therapy platforms, raising \nquestions about potential pathogenic mechanisms and HRP.\nProactive and modernized safety \nsurveillance programs including:\nBlood- and tissue- based monitoring\nEpidemiologic studies\nAI-driven analyses using reliable, \nstandardized datasets\nExpanded autopsy programs to clarify causality in serious outcomesPrograms that systematically evaluate COVID -19 vaccine safety\nFDA approval policies calibrated to gene therapy –like risks; DNA limits\nStronger pharmaceutical accountability\nCDC guidelines ensuring transparent risk disclosure, mitigation strategies, and robust informed consentCOVID Vaccine Summary & Recommendations", "summary": "Wafik El-Deiry , MD, PhD, FACP Director, Legorreta Cancer Center Associate Dean, Oncologic SciencesWarren Alpert Medical School, BrownUniversity September 19, 2025 Workgroup Safety Uncertainties of mRNA  COVID Vaccines Charlotte Kuperwasser, PhD Director, Tufts Convergence Laboratory of  Biomedical, Physical, and Engineering SciencesProfessor Developmental, Molecular & Chemical Biology, Tufts University School of Medicine  TERMS OF REFERENCE # 6, 7 & 8 1.Immune Changes   2.Biodistribution…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-september-18-19-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-09-18-19/06-el-deiry-kuperwasser-covid-508.pdf", "doc_date": "2025-09-18", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 16}
{"title": "07 carleton covid 508", "content": "Genomics of Vaccine -Induced Myocarditis\nBruce Carleton\nProfessor and Chair, Division of Translational Therapeutics, Department of Pediatrics, \nProfessor of Pediatrics, Medical Genetics, Pharmaceutical Sciences, Population and Public Health \nUniversity of British Columbia\nClinical Pharmacology Lead, MedSafe  Clinics, BC Children’s and  St Paul’s Hospitals\nSenior Clinician Scientist, BC Children’s Hospital Research Institute \nVancouver, Canada\nDr.Carleton has received financial support forgenomics research from the \nfollowing government and non -profit sources:\nCanadian Institutes ofHealth Research, Genome Canada, Genome British\nColumbia, Genome Alberta, Génome  Québec, Ontario Genomics, Health Canada,\nBCChildren’s Hospital Foundation, BCProvincial Health Services Authority , \nMichael Smith Foundation for Health Research, USCenters forDisease Control\nandPrevention , and the Coalition for Epidemic Preparedness Innovations (CEPI) .\nThe work today was funded by a grant to the Global Vaccine Data Network (GVDN) \nprovided by the US Centers for Disease Control.\nHeisapast consultant totheUnited Health Group , Dynacare Next Specialized\nDiagnostics andNeopharm Labs regarding pharmacogenetic testing.\nThis work was \nfunded by a grant \nto the Global \nVaccine Data \nNetwork (GVDN)\nSteve Black MD,  Helen Petousis -Harris PhD, Jim Buttery MD\nCo-Directors\n\nthe GVDN: \nA collaborative Network of  32 countries and growing \nArgentina\nAustralia\nBrazil\nCanada\nChile\nChina\nDenmark\nEnglandEthiopia\nFinland\nFrance\nGhana\nHong Kong\nIndia\nIndonesiaJapan\nKorea, Republic of\nNew Zealand\nScotland\nTaiwan\nUSA\nVAC4EUSouth Africa\n and the \nAlive collaboration \ncountries: DRC Congo\nEthiopia, Ghana, \nKenya, Malawi, \nMali, Mozambique, \nNigeria , Rwanda\nCOVID -19 mRNA Vaccine -induced Myocarditis \nExome Sequencing Cohort\nClinical Elements for Brighton Collaboration Level 1 Myocarditis Cases ( N=50)\nAge, [Mean (SD); range]\n[Median; IQR]26.5 (13.5); 11 to 83 yr\n21.5 yr; 18 to 31 yr\nBiological sex, n (%) Male ( n=40, 80%), Female ( n=10, 20%)\nSelf-reported ancestry, nEuropean ( n=31); Australian ( n=7); \nUnknown (not reported) ( n=7); Egyptian ( n=1); \nLebanese ( n=1); Admixed American ( n=1); \nIndian ( n=1); South African ( n=1)\nVaccine manufacturer, n (%) Pfizer ( n=37, 74%); Moderna ( n=13, 26%)\nDose, n (%)1st does ( n=10, 20%); 2nd dose ( n=36, 72%); \n3rd dose ( n=4, 8%)\nVaccination to onset of myocarditis \nsymptoms, [Median; IQR]*4 days; 3 to 26 \n*available for 30 patients only \nMethods\n•50 Brighton Collaboration Level 1 myocarditis cases were sequenced\n•Exome -captured library preparation was sequenced with the Illumina \nNovaSeq  6000 system, reaching an average depth of 100x\n•Reads were aligned to the GRch38 human reference genome\n•49 of 50 samples passed the quality control process\n•Examine variant frequencies ≥ 50% in cases when global allele \nfrequency ( ClinVar ) is ≤ 15%\n7 variants across four genes identified with \nclear linkage to myocarditis development\nNo. Gene Function SNP IDMinor allele \nfrequency (n=49)Global allele frequency \n(n=5,008)Fisher's exact \nP-valueOdds ratio\n(95% CI)\n1 LRP8 Missense rs5174 0.398 0.144 (T) 9.58x10-10 3.92 (2.53 - 5.99)\n2 VKORC1 Intron rs2884737 0.306 0.0914 (C) 2.44x10-9 4.38 (2.74 - 6.87)\n3 AGTR1 3 Prime UTR rs5186 0.327 0.118 (C) 5.34x10-8 3.63 (2.29 - 5.64)\n4 ACAN Missense rs3817428 0.316 0.114 (G) 9.56x10-8 3.59 (2.25 - 5.60)\n5 SUMF1 Missense rs2819590 0.306 0.117 (T) 5.24x10-7 3.34 (2.09 - 5.23)\n6 WDR62 Synonymous rs2301734 0.316 0.125 (A) 6.93x10-7 3.24 (2.04 - 5.05)\n7 TTN Missense rs36051007 0.316 0.126 (T) 8.22x10-7 3.21 (2.02 - 5.00)\n8 TTN Missense rs35833641 0.316 0.127 (G) 9.74x10-7 3.18 (2.00 - 4.96)\n9 ANHX Missense rs36146434 0.316 0.129 (C) 1.40x10-6 3.12 (1.96 - 4.86)\n10 ALPP Missense rs1048988 0.327 0.141 (C) 3.02x10-6 2.96 (1.87 - 4.60)\n11 TTN Missense rs12463674 0.310 0.130 (G) 3.25x10-6 3.01 (1.89 - 4.68)\n12 EDARADD 3 Prime UTR rs6428955 0.316 0.138 (T) 5.75x10-6 2.90 (1.82 - 4.51)\n13 MCPH1 Intron rs1961222 0.330 0.150 (T) 7.24x10-6 2.80 (1.78 - 4.32)\n14 MSH6 Missense rs1800935 0.306 0.135 (C) 1.12x10-5 2.82 (1.77 - 4.42)\n15 CHRNA5 Missense rs16969968 0.316 0.150 (A) 4.47x10-5 2.63 (1.65 - 4.10)\n16 SUGP1 Stop Gained rs11555053 0.306 0.149 (A) 8.74x10-5 2.52 (1.57 - 3.94)\n17 VPS53 Missense rs11558129 0.296 0.145 (A) 0.000138 2.47 (1.54 - 3.88)\n18 TTN Missense rs12464787 0.296 0.147 (A) 0.000152 2.45 (1.53 - 3.84)\nAn increase in the number of homozygous risk \nvariants shortens the time to onset of myocarditis\n\nLRP8 (LDL Receptor Related Protein 8)\n•Expressed in the heart, endothelium, vascular smooth muscle, and \nplatelets\n•R952Q variant (rs5174) is linked to cardiovascular inflammation and \nimmune response, particularly in coronary artery disease (CAD) and \nmyocardial infarction (MI) (OR: 1.31 –1.42, P<0.05)\n•Among 49 Brighton Level 1 myocarditis cases, 10 are homozygous for \nthe risk allele (TT) and 19 are heterozygous (CT) for rs5174.\nAGTR1 (Angiotensin II Type 1 Receptor) \n•Patients with AGTR1 rs5186 risk CC genotype display both increased \nLDL and triglycerides \n•AC and CC genotypes are associated with ≥90% left anterior \ndescending artery stenosis [OR: 1.94 (1.059 -3.552, P=0.032)]. \n•The C allele is associated with MI susceptibility [OR:1.12 (1.01 -1.25); \nP=0.03] and essential arterial hypertension severity ( P=0.033).\n•Among 49 Brighton Level 1 myocarditis cases, 4 are homozygous for \nthe risk allele (CC) and 24 are heterozygous (AC) for rs5186.\nLRP8 & AGTR1 in Renin -Angiotensin System (RAS) \nAGTR1\nrs5186\nAngiotensin II\nHypertension; \nVasoconstriction; \nCardiac hypertrophy\nRef: Curr Treat Options Oncol. 2024;25(11):1406 -1427ApoELRP8\nrs5174\np38 MARK pathway\nactivation\nCardiovascular \ninflammationApoE\nVKORC1  \n(Vitamin K Epoxide Reductase Complex Subunit 1)\n•Highly expressed in the heart\n•Key element of vitamin K signaling and warfarin dosage\n•The rs2884737 C allele is associated with increased sensitivity to \nwarfarin dose compared to the wild -type A allele\n•VKORC1 haplotypes are associated with arterial vascular diseases \n(e.g., stroke, coronary heart disease, and aortic dissection)\n•Among 49 Brighton Level 1 myocarditis cases, 3 are homozygous for \nthe risk allele (CC) and 24 are heterozygous (AC) for rs2884737\nVKORC1\nRef: Pharmacol  Rev. 2013;65(3):987 -1009VKORC1\nrisk haplotypes\nPrevent vascular calcification\nPrevent atherosclerosis\nTTN (Titin)\n•TTN variants are the most frequent cause of dilated cardiomyopathy \nand account for 25% of familial and 18% of idiopathic cases\n•TTN is associated with acute myocarditis, with a higher variant \nprevalence in cases (6%) than in controls (1% -2.9%) ( P=0.019).\n•Among 49 Brighton Level 1 myocarditis cases, 3 are homozygous for \nall four variants, 2 are homozygous for three variants, and 21 are \nheterozygous for all four variants.\nConsequences of TTN variants\nTTN variants\nRef: Nat Rev Cardiol . 2018;15(4):241 -252.\nPlanned Next Steps\n•Before the GVDN grant was cancelled\noGoal: 275 cases per each adverse event \nand 2,750  controls per vaccine \nplatform (a total of 5,500  controls for \nboth mRNA and adenoviral vector -\nbased platforms)  \n•Further analysis and verification of the exome sequencing data \n•Genome -wide analysis for the full cohort of myocarditis (+/ - pericarditis and \nmyopericarditis) will be conducted once the target enrollment is reached\n•Exome analysis of vaccine -induced immune thrombotic thrombocytopenia (VITT) will be \nconducted in a subset of patients with the highest certainty of being vaccine -induced\n•Genome -wide analysis for the full cohort of VITT will be conducted once the target \nenrollment is reached. Adverse event Expected # Enrolled #\nMyocarditis 422 207 (195 mRNA)\nPericarditis 301 47 (39 mRNA)\nMyopericarditis 273 36 (32 mRNA)\nVITT 235 81 (51 AVV)\nGBS 154 37  (27 AVV)\nControl 4,9601,967 (1,005 mRNA & 804 \nAVV)\nA final word about vaccine genomics\n•Genomics studies of drugs have revolutionized drug \ntherapy allowing for personalized approaches to \ntreatment.  More than 500 FDA -approved drugs have \ngenetic information annotated in their labels.\n•Identifying genetic markers of risk for vaccine adverse \nevents would serve two purposes:\n•Facilitating a better understanding of the \npathophysiology of events\n•Allow for personalized vaccine schedules that \nreduce the risk of AEFIs.\nGVDN  |  A coordinated program of vaccine safety activities", "summary": "Genomics of Vaccine -Induced Myocarditis Bruce Carleton Professor and Chair, Division of Translational Therapeutics, Department of Pediatrics,  Professor of Pediatrics, Medical Genetics, Pharmaceutical Sciences, Population and Public Health  University of British Columbia Clinical Pharmacology Lead, MedSafe  Clinics, BC Children’s and  St Paul’s Hospitals Senior Clinician Scientist, BC Children’s Hospital Research Institute  Vancouver, Canada Dr.Carleton has received financial support…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-september-18-19-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-09-18-19/07-carleton-covid-508.pdf", "doc_date": "2025-09-18", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 17}
{"title": "08 Srinivasan covid 508", "content": "Economic Analysis of\nCOVID -19 Vaccination\nUniversity of Michigan \nCOVID -19 Vaccination Modeling Team\nPresentation to the Advisory Committee on Immunization Practices\nSeptember 19, 2025\n1\nStudy team\n•University of Michigan\n•Wake Forest University\n•Centers for Disease Control and Prevention\n2Conflict of interest statement\nNo known conflicts of interest. \nEconomic Analysis of COVID -19 Vaccination: Objectives\nUsing an economic model of COVID -19 vaccination:\n•Estimate  the annual population burden of disease in a cohort representing the US \npopulation\noresource utilization (outpatient visits, hospitalizations ) \nototal cases\nototal costs\nodeaths\noquality -adjusted life years lost due to COVID -19\n•Estimate events averted by COVID -19 vaccination\n•Estimate incremental cost -effectiveness ratios for subgroups defined by age and risk \nstatus\n3Earlier analyses from this model were presented to ACIP in September 2023, February 2024, June 2024, and October 2024: Prosser , Lisa A. (2023). Economic Analysis \nof Vaccination with mRNA Booster Dose against COVID -19 Among Adults; Prosser, Lisa A (2024). Economic analysis of an additional dose of COVID -19 vaccine; Prosser, \nLisa A. (2024). Economic analysis of COVID -19 vaccination; Prosser, Lisa A. (2024). Economic analysis of an additional dose of t he 2024 -2025 COVID -19 vaccine.\nMethods\n•Intervention strategies:\noVaccination against COVID -19 illness with an updated “generic” mRNA booster\noNo updated mRNA booster (vaccination against COVID -19 illness with primary series only or \nprimary series plus current booster)\n•Target population: all US adults, stratified by age and risk status\no18-49 y, 50 -64 y, ≥65 y\noHigh risk or not at high risk for complications\noPediatric and adolescent age groups excluded  from current analysis, insufficient data to \nincorporate into this first phase analysis\n•Time horizon: 1 year*\n•Perspective: Societal\n•Costing year: 2024$\n•Discount rate: 3%\n*Costs and QALYs lost due to long -term sequelae and deaths beyond one year are included 4\nSymptomatic \nCOVID -19\n(non -hospitalized) \nHospitalized\nCOVID -19Non -medically \nattended\nOutpatient visit\nNo ICU \nadmission\nICU admissionAB\nNo \ncomplications\nLong COVID \nNo ventilator\nVentilatorB\nDDeathModel \nschematic\nNo\nCOVID -19\nCOVID -19No long COVID\nLong COVID\nLong -term \nsequelae C\nNo \ncomplications\nLong COVID \nDeath\n5ED visit B\nED = emergency department; ICU = intensive care unit\nProsser et al. Cost -effectiveness of 2023 -2024 COVID -19 vaccination in US adults. JAMA Network Open. 2025 Aug 1;8(8):e2523688.No ventilator\nVentilator C\nD\nUpdated COVID -\n19 vaccinationNo side \neffects\nSystemic \nreaction\nAnaphylaxis\nSevere \nadverse eventA\nA\nANo updated \nCOVID -19 \nvaccination\nA\nEpidemiological inputs\n6Input Source\nProbability of symptomatic illness HEROES -RECOVER \n(2022 – 2023)\nProbability of medically attended illness MarketScan\n(2022)\nProbability of hospitalization COVID -NET (2023 - 2024), \nexpert opinion\nProbability of ICU stay and ventilator use COVID -NET\n(2022 – 2023)\nProbability of death COVID -NET\n(2022 – 2023)\nProbability of long -term sequalae Published literature\nProbability of long COVID Published literature\n020406080100120140\nOct Nov Dec Jan Feb Mar Apr May Jun Jul Aug SepMonthly hospitalizations per 100,000Weekly rates of \nCOVID -19– \nassociated \nhospitalizations \nby season, all \nages\n72021 -2022\n2020 -2021\n2019 -20202022 -2023\n2024 -2025\nSource: COVID -NETBase case (2023 -2024)\nVaccination -related parameter inputs\n8Input Source\nSeasonality -adjusted vaccine impact (SAVI) VISION (2024 – 2025), \nIVY (2024 – 2025), \nCOVID -NET (2023 – 2024),\nexpert opinion\nProbabilities of adverse events\n•Systemic reaction\n•Anaphylaxis\n•Myocarditis/pericarditisFDA product approval \ninformation, published \nliterature, expert opinion\nCosts\n9Input Source\nIllness -related\nDirect medical costs\n•Outpatient visits\n•ED visits\n•Hospitalizations\n•Long -term sequalae\n•Long COVIDMarketScan  2022 -2023, \npublished literature\nProductivity lossesBLS, published literature, expert \nopinion\nVaccination -related\nDirect medical costs:\n•Vaccine dose\n•Administration\n•Adverse eventsCDC vaccine price list\nPhysician fee schedule\nPublished literature, expert opinion\nTime costs of vaccination Published literature\nBLS = Bureau of Labor Statistics\nQuality of life adjustments\n10Input Source\nIllness -related\n•Symptomatic illness\n•Hospitalization\n•Long -term sequalae\n•Long COVIDPublished literature\nVaccination -related\n•Systemic reaction\n•Anaphylaxis\n•Myocarditis/pericarditisPublished literature\nMethods: Analysis Plan\n•Project health and economic outcomes stratified by intervention strategy, age (18-\n49 y, 50 -64 y, ≥65 y) and risk subgroups (high risk, non -high risk)\noCases\noHospitalizations\noDeaths\noCosts\noQuality -Adjusted Life -Years  (QALYs)\noAdverse events\noNumber needed to vaccinate (NNV)\n11\nMethods: Analysis Plan\n•Incremental cost -effectiveness ratio (ICER):\n   CostsUpdated  Vaccination  – CostsNo Updated Vaccination\n  QALYsUpdated  Vaccination  – QALYsNo Updated Vaccination\n•Base case analysis\n•Sensitivity analyses\n•Probabilistic sensitivity analysis\n•Univariate and multi -way sensitivity analyses\n•Scenario analyses\n1212\nResults*\n13*This presentation reports preliminary results of an ongoing analysis\nDisaggregated results, per 100,000 simulated cohort, \nsocietal perspective, 2025 -2026 vaccination\n140500010000150002000025000300003500040000\n18-49 NHR 50-64 NHR >65 NHR 18-49 HR 50-64 HR >65 HRCases\n020040060080010001200\n18-49 NHR 50-64 NHR >65 NHR 18-49 HR 50-64 HR >65 HRHospitalizations\n020406080100120140160\n18-49 NHR 50-64 NHR >65 NHR 18-49 HR 50-64 HR >65 HRICU Stays\n0102030405060\n18-49 NHR 50-64 NHR >65 NHR 18-49 HR 50-64 HR >65 HRDeaths - 100 200 300 400 500 600\n18-49 NHR 50-64 NHR >65 NHR 18-49 HR 50-64 HR >65 HRCases of Long COVID\nRemaining events with vaccination, NHR\n          Events averted with vaccination, NHR\n          Remaining events with vaccination, HR\n          Events averted with vaccination, HR\n          HR = high risk; NHR = non -high risk\n\nIncremental cost -effectiveness ratios (ICERs), 2025 -2026 \nvaccination, per cohort of 1,000,000\n15Age Strategy CostIncremental \ncostQALYsIncremental \nQALYs$/QALY\nNon -high -risk\n18 - 49 yNo vaccination $121,084,319 - 20,208,352 - -\nVaccination $292,804,184 $171,719,865 20,208,697 345 $498,090\n50 - 64 yNo vaccination $172,993,823 - 12,278,283 - -\nVaccination $329,875,771 $156,881,948 12,278,676 393 $398,809\n>65 yNo vaccination $213,552,333 - 6,526,870 - -\nVaccination $345,570,759 $132,018,426 6,527,758 887 $148,811\nHigh -risk\n18 - 49 yNo vaccination $166,726,302 - 20,208,138 - -\nVaccination $323,381,110 $156,654,808 20,208,555 417 $375,399\n50 - 64 yNo vaccination $295,589,269 - 12,277,500 - -\nVaccination $411,159,262 $115,569,993 12,278,163 663 $174,359\n>65 yNo vaccination $395,948,683 - 6,524,593 - -\nVaccination $467,984,279 $72,035,596 6,526,248 1655 $43,537\nQALY = quality -adjusted life year\nBase -case and probabilistic sensitivity analyses, 2025 -2026 \nvaccination\nAgeICER ($/QALY)\nBase case 95% confidence interval\nNon -high -risk\n18 - 49 y $498,090 $309,220 - $913,905\n50 - 64 y $398,809 $252,690 - $691,360\n>65 y $148,811 $78,132 - $276,981\nHigh -risk\n18 - 49 y $375,399 $232,241 - $659,757\n50 - 64 y $174,359 $66,920 - $388,115\n>65 y $43,537 Cost -saving - $142,478\n16ICER = incremental cost effectiveness ratio; QALY = quality -adjusted life year  \nNumber needed to vaccinate (NNV), 2025 -2026 vaccination, \nbase case\nAgeNNV to\navert a caseNNV to\navert a \nhospitalization NNV to\navert a death \nNon -high -risk\n18 - 49 y 15 15,746 1,133,330\n50 - 64 y 16 4,897 145,755\n>65 y 12 778 14,818 \nHigh -risk\n18 - 49 y 15 3,351 241,229 \n50 - 64 y 16 1,227 36,522 \n>65 y 12 296 5,642 \n17\nCost/outcome averted, 2025 -2026 vaccination, base case\nAge $/Case averted$/Hospitalization \naverted$/Death averted\nNon -high -risk\n18 - 49 y $2,504 $2,703,838 $194,615,325\n50 - 64 y $2,474 $768,180 $22,866,393\n>65 y $1,540 $102,729 $1,956,219\nHigh -risk\n18 - 49 y $2,282 $525,021 $37,789,676\n50 - 64 y $1,817 $141,797 $4,220,853\n>65 y $836 $21,344 $406,450\n18\nOne-way sensitivity analysis, >65 years, non -high -risk\n19$/QALY gained with variable at upper bound $/QALY gained with variable at lower bound$0 $100,000 $200,000 $300,000 $400,000Time to receive vaccine, pharmacyProbability, outpatient visit given symptomatic COVIDCost, vaccine administrationLifetime productivity costTime to receive vaccine, doctor's officeProbability, symptomatic illnessQuality adjustment, symptomatic COVIDCost, vaccine doseProbability, hospitalizationSAVI against symptomatic COVID, hospitalization, critical illness\n$/QALY\nBase case: $148,811/QALY\nSAVI = seasonality -adjusted vaccine impact\nOne-way sensitivity analysis: probability of hospitalization\nAgeICER ($/QALY)\nLower bound Base case Upper bound\nNon -high -risk\n18 - 49 y $526,249 $498,090 $466,186\n50 - 64 y $501,595 $398,809 $306,095\n>65 y $267,505 $148,811 $81,894\nHigh -risk\n18 - 49 y $477,426 $375,399 $284,883\n50 - 64 y $368,234 $174,359 $68,386\n>65 y $157,467 $43,537 Cost -saving\n20ICER = incremental cost effectiveness ratio; QALY = quality -adjusted life year  \nScenario analysis: vaccine dose cost, 2025 -2026 vaccination\nAgeICER ($/QALY)\n$30 $60 $90 $120 Base case $150\nNon -high -risk\n18 - 49 y $181,113 $268,131 $355,149 $442,166 $498,090 $529,184\n50 - 64 y $121,009 $197,272 $273,535 $349,798 $398,809 $426,061\n>65 y $25,631 $59,447 $93,262 $127,078 $148,811 $160,894\nHigh -risk\n18 - 49 y $113,526 $185,417 $257,307 $329,198 $375,399 $401,088\n50 - 64 y $9,490 $54,750 $100,011 $145,272 $174,359 $190,532\n>65 y Cost -saving Cost -saving $13,753 $31,885 $43,537 $50,016\n21ICER = incremental cost effectiveness ratio; QALY = quality -adjusted life year\nBase case: $139.28\nAge >18 private sector prices: Moderna $141.80; Pfizer $136.75   \nAccounting for Vaccine Wastage in Cost -\neffectiveness Analyses\n22•Few CEAs include wastage as a separate cost in the analysis \n•Conventional assumption is that any costs associated with wastage are \nreflected in the price per dose (if returns are allowed) or the administration \nfee (if provider bears the cost of unused doses)\n•Scenario analysis on price per dose yields insights if wastage is not adequately \ncaptured by base case assumptions\nLimitations\n23•Unpublished data used to derive key parameters in the model: vaccine \neffectiveness, symptomatic illness, probabilities of hospitalization and \ncritical illness\n•Data sources vary in representativeness, generalizability\n•VE estimates derived from single prior season data \n•Few seasons to date to estimate seasonality\n•MarketScan  data for ages >65 y only includes those with supplemental \ninsurance\n•Evidence base for long COVID is especially scarce\n•Model does not include reduced transmission (conservative approach) \nSummary\n•Vaccination averts morbidity and mortality for all age and risk groups\n•Substantial variation in impact by age and risk status\n•Overall economic favorability has declined compared to estimates from earlier \nseasons due to declining burden of illness\n•ICERs for ≥65 y age group [HR: $44,000/QALY; NHR: $149,000/QALY] are robust to \nchanges in parameter inputs across plausible ranges [HR: Cost -saving -$142,000/QALY; \nNHR: $78,000/QALY -$277,000/QALY]\n•ICERs for 18 -49 y and 50 -64 y age groups are sensitive to changes in parameter \ninputs and favorable only under certain conditions for high -risk 50 -64 y\n24\nQuestions\n25", "summary": "Economic Analysis of COVID -19 Vaccination University of Michigan  COVID -19 Vaccination Modeling Team Presentation to the Advisory Committee on Immunization Practices September 19, 2025 1 Study team •University of Michigan •Wake Forest University •Centers for Disease Control and Prevention 2Conflict of interest statement No known conflicts of interest.  Economic Analysis of COVID -19 Vaccination: Objectives Using an economic model of COVID -19 vaccination: •Estimate  the annual population…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-september-18-19-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-09-18-19/08-Srinivasan-covid-508.pdf", "doc_date": "2025-09-18", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 25}
{"title": "10 levi COVID 508", "content": "ACIP Meeting, CDC\nSeptember 19, 2025COVID -19 Vaccine Discussion \nFraming, 2025-2026\nProfessor Retsef Levi, PhD, MIT\nACIP Meeting, CDC\nSeptember 19, 2025WG Main Takeaways\n•Assessments of the protection level provided by COVID -19 vaccines and especially \nseasonal boosters against severe outcomes (hospitalization, ICU, death, long- covid) \nare based on very low -quality data and analyses\n•Vaccine injuries are demonstrably not recognized by current pharmacovigilance \nsystems, leaving vaccine injured individuals abandoned and without appropriate care   \n•Ample published research suggests serious safety uncertainties and concerns, including potential adulteration (mRNA vaccines), that are currently not appropriately addressed\nACIP Meeting, CDC\nSeptember 19, 2025WG Recommended Actions\n•The risks and uncertainties related to the COVID -19 vaccine should be appropriately \ncommunicated by CDC to patients and medical providers to enable appropriate informed \nconsent (WG recommendations regarding the Vaccine Information Statement) \n•Development and enhancement of national efforts to appropriately diagnose the vaccine injured and care for them (WG will continue discussions in coming months)\n•Development and enhancement of national safety surveillance systems to address safety uncertainties and assess impact (WG will continue discussions in the coming months)\nACIP Meeting, CDC\nSeptember 19, 2025COVID-19 Vaccine Benefits: Quality of Evidence \nThe WG could not receive reliable assessments of the Number Needed to Vaccinate \n(NNV) related to different sub- groups and outcomes:\nPresentation to COVID -19 Work Group September 12, 2025 by the University of Michigan\nACIP Meeting, CDC\nSeptember 19, 2025Quality of Evidence re COVID -19 Vaccine Benefits\nEstimates from the UK greatly differ from the CDC estimates:\nUK Health Security Agency (UKHSA) NVV estimates for the \n2024- 2025 season\nAppendix A: estimating the number needed to vaccinate to \nprevent a COVID -19 hospitalisation  in autumn 2024 in \nEngland - GOV.UK\n\nACIP Meeting, CDC\nSeptember 19, 2025Quality of Evidence re COVID -19 Vaccine Benefits\nEstimates from the UK greatly differ from the CDC estimates:\nUK Health Security Agency (UKHSA) NVV estimates for the 2024 -2025 \nseason\nAppendix A: estimating the number needed to vaccinate to prevent a \nCOVID -19 hospitalisation  in autumn 2024 in England - GOV.UK\n\nACIP Meeting, CDC\nSeptember 19, 2025Methodological Limitations \n•WG members felt that the current working definition of the CDC regarding COVID -19 \nassociated hospitals does not seem to meaningfully capture the clinical impact of \nSARS- CoV-2 infections on severe COVID -19 outcomes\n•Only 30% of patients under current definition have COVID as primary discharge diagnosis \nTrends in COVID -19–Attributable Hospitalizations Among Adults With Laboratory -Confirmed SARS -CoV -2—COVID -NET, June \n2020 to September 2023 - Taylor - 2024 - Influenza and Other Respiratory Viruses -  Wiley Online Library\nACIP Meeting, CDC\nSeptember 19, 2025Methodological Limitations \n•WG members felt that the current methodology to assess vaccine efficacy (VE) is \nprone to major biases:\n“The design cannot be used for studying the mortality effects of vaccines and is \nproblematic for studies into the effect on hospitalization. The vaccine's effectiveness on the transmission of viruses is also potentially problematic, depending very much on the characteristics of the tests. The implication of our findings is that the test -negative \ndesigns can, at best, be seen as an indication of effectiveness in highly idealized situations that are often far away from reality.”\nhttps://onlinelibrary.wiley.com/doi/10.1111/jep.13888\n \nACIP Meeting, CDC\nSeptember 19, 2025Test-Negative- Design\nN = population size= Nv + Nuv  \nUnknown number of vaccinated \n(Nv) and unvaccinated (Nuv) \nCv = # of vaccinated \ncovid cases Cuv = # of unvaccinated \ncovid cases Ov = # of vaccinated \ncontrolsOuv = # of unvaccinated \ncovid controls\nACIP Meeting, CDC\nSeptember 19, 2025NTD - Main Idea\n•Ideally the relative risk would be calculated as 1- (Cv/Cuv)÷(Nv/Nuv), but Nv/Nuv not \nobserved!\n•Approximate it with the observed Ov/Ouv assuming the control cases are not affected \nby/correlated with vaccination status and therefore are drawn at random from the \npopulation\n•Attempt to mitigate biases because health- seeking behavior (people who arrived to \nthe hospital)\n•Under assumptions provide an unbiased estimator of the relative risk reduction \nACIP Meeting, CDC\nSeptember 19, 2025Potential Biases of NTD\n•The estimate of Ov/Ouv (for unobserved Nv/Nuv) is prone to many biases:\n•Hospitalizations of controls (and cases) might be triggered by other (non-\nrespiratory) medical conditions\n•Vaccinated test more when they have a cold \n•Vaccine could make vaccinated more vulnerable to other cold infections \n•Healthy vaccinee effect (HVE)\nhttps://www.nejm.org/doi/full/10.1056/NEJMc2306683\nACIP Meeting, CDC\nSeptember 19, 2025Other VE Assessment Approaches\n•Matched cases (exact on based on propensity scores)\n•Use of negative controls to capture unobserved biases\n•Randomized control clinical trials (RCTs)\nNote: \nRCTs of mRNA vaccines did not show benefits for all cause mortality & hospitalizations\nhttps://pubmed.ncbi.nlm.nih.gov/37163200/\nhttps://pubmed.ncbi.nlm.nih.gov/36055877/\n \nACIP Meeting, CDC\nSeptember 19, 2025Other Concerns regarding VE\n•WG members were concerned that the boosters’ protection seems to be short -term\n•WG members were concerned by published and unpublished research that suggest \nnegative efficacy or increased vulnerability to other respiratory viruses:\nhttps://academic.oup.com/ofid/article/10/6/ofad209/7131292?login=false\nhttps://www.nature.com/articles/s43856- 025-01046-8\nhttps://www.medrxiv.org/content/10.1101/2023.12.07.23298573v3\nACIP Meeting, CDC\nSeptember 19, 2025COVID- 19 Burden Decreases \nPresentation to COVID -19 Work Group September 12, 2025 by the University of Michigan\n\nACIP Meeting, CDC\nSeptember 19, 2025Safety Concerns and Uncertainties\nWG members felt that CDC currently does not appropriately acknowledge several \nsafety concerns & uncertainties:\n•Outcomes and prognosis of myocarditis and other cardiovascular adverse events\n•Clinically documented prolonged vaccines injuries, specifically post vaccine syndrome (PVS)\n•Multiple documented unintended mechanisms of action of the mRNA vaccines and seemingly regulatory violations\nACIP Meeting, CDC\nSeptember 19, 2025Deaths from Myocarditis\nAutopsies of 2 teenage boys in the US who died in their sleep 3 & 4 days \npost Pfizer Dose 2\n\nACIP Meeting, CDC\nSeptember 19, 2025Deaths from Myocarditis\nCDC response\n\nACIP Meeting, CDC\nSeptember 19, 2025Deaths from Myocarditis\nPathologist response\n\nACIP Meeting, CDC\nSeptember 19, 2025Subclinical myocarditis may occur in up to 3% post vaccination  \nTeenage boys post dose 2\nAdult healthcare workers post booster \ndose\n\nACIP Meeting, CDC\nSeptember 19, 2025Deaths from Subclinical Myocarditis\nKorean study of 44 million vaccinated\n•95 cases severe vaccine related myocarditis\n•85 ICU admissions\n•36 cases of fulminant myocarditis\n•21 deaths (12 males & 9 females)\n•8 of the deaths were sudden cardiac death \nautopsy -found myocarditis without prodrome \n(subclinical myocarditis)  all in <45 year olds who \nhad received mRNA vaccines\nACIP Meeting, CDC\nSeptember 19, 2025Long Term Prognosis of Myocarditis\nUnknown if this will apply to COVID -19 \nvaccine associated myocarditisHigher risk (almost 2.5 fold) of CV death 10 years after a myocarditis diagnosis\nACIP Meeting, CDC\nSeptember 19, 2025Post Vaccine Syndrome (PVS)\n•The injuries associated with PVS are prolonged, debilitating and involve diverse \nsymptoms and conditions, many overlapping with long COVID injuries \n•Symptoms include among others dysautonomia (POTS), immune dysregulation, autoimmune disorders, severe neuropathy, cardiovascular & neurovascular injuries and severe clotting\nACIP Meeting, CDC\nSeptember 19, 2025Post Vaccine Syndrome (PVS)\n•The frequency of PVS and related risk factors are currently not well understood\n•Do not fit existing diagnosis codes and often have common post vaccination \nsymptoms but prolonged, therefore not likely to be captured by existing pharmacovigilance systems\nIdentification of Potential Adverse Events After COVID -19 mRNA Vaccines in Danish Children Using Healthcare Registries\nACIP Meeting, CDC\nSeptember 19, 2025mRNA Vaccines Don’t Work as Intended\n•Wide biodistribution and prolonged persistent \nof Spike, mRNA and nano-lipid particles\n•Not understood prolonged immune response (e.g., IgG4 switch class and cytokine profile)\n•Frame shift leading to production of unintended proteins and related immune \nresponse\n•DNA contamination (regulatory violation)\n\nACIP Meeting, CDC\nSeptember 19, 2025Vaccination in Pregnancy\nMost WG members felt that the current data not only do not support recommendation \nto vaccinate during pregnancy, but to the contrary support NOT to recommend:  \n•No appropriate randomized clinical trials to show efficacy and safety\n•In the single (small) clinical trial (Pfizer) there was observed numerical imbalance of higher number of fetal anomalies among babies born to vaccinated women (8 vs. 2)\nACIP Meeting, CDC\nSeptember 19, 2025Vaccination in Pregnancy\n•Observational studies are of very low -quality with structural biases, and some raise \nconcerns\nhttps://pubmed.ncbi.nlm.nih.gov/36794918/\nhttps://obgyn.onlinelibrary.wiley.com/doi/10.1111/1471-0528.17721\nhttps://bmcpregnancychildbirth.biomedcentral.com/articles/10.1186/s12884-025-07784- w\n  \nACIP Meeting, CDC\nSeptember 19, 2025Vaccine -Specific Recommendations\nThe WG felt that there weren’t sufficient data and time to arrive at recommendations specific to \na vendor or a platform, but this seems likely to be a plausible approach in the future: \n•In RCTs adenovirus vaccines reduced all cause mortality vs. mRNA vaccines that didn’t\nhttps://pubmed.ncbi.nlm.nih.gov/37163200/\n•Studies show Moderna may have higher protection and lower AEs compared to Pfizer\nhttps://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2793236\nhttps://www.nejm.org/doi/full/10.1056/NEJMoa2115463\n•Other vaccines, including not currently authorized in the US should be evaluated \nACIP Meeting, CDC\nSeptember 19, 2025Public Trust\nMembers in the WG felt that there a concerning gap between CDC ‘safe and effective’ \nnarrative and public perception that erodes trust: \n•In a recent poll over 56% suspect COVID -19 vaccines caused death: \nhttps://www.rasmussenreports.com/public_content/politics/trump_administration_second_term/56_suspect_covid_19_vaccines_caused_deaths\n•In another poll, 25% think they know someone who died from COVID -19 vaccines\nhttps://issuu.com/indiabookofrecords/docs/chugalkhor_times_mar_2023_issue_4/s/20904385\nACIP Meeting, CDC\nSeptember 19, 2025Trust of Healthcare Workers\n\nACIP Meeting, CDC\nSeptember 19, 2025Discussion of the Recommendations \nfor ACIP Vote\nACIP Meeting, CDC\nSeptember 19, 2025Recommended Updates to the Vaccine Information Statement\nMost of the WG members were concerned that the existing administration processes of the \nCOVID -19 vaccination products do not ensure a meaningful informed consent:\n\nACIP Meeting, CDC\nSeptember 19, 2025Recommended Updates to the Vaccine Information Statement\n“To inform is not merely to provide written or verbal notification of risks and benefits. \nInformation disclosures, both in their content and mode of delivery, must spur earnest \ncontemplation and autonomous decision-making.” \n“Each VIS must have a description of a vaccine’s 1) benefits, 2) risks, 3) a statement of \navailability of the VICP, and 4) any other information deemed relevant. VISs must be presented \nbefore every vaccine dose in all clinical settings, regardless of whether there is a learned intermediary present or not.”\n\nACIP Meeting, CDC\nSeptember 19, 2025Recommended Updates to the Vaccine Information Statement\nThe WG recommendation is that the CDC engages in effort to create more \nconsistent and comprehensive informed consent processes, and as part of that \nconsiders adding language accessible to patients and medical providers to \ndescribe the following risks and uncertainties:\nACIP Meeting, CDC\nSeptember 19, 2025Recommended Updates to the Vaccine Information Statement\n1.Current assessments regarding the protection provided by COVID -19 \nvaccines and especially seasonal COVID -19 boosters against severe \noutcomes (e.g., death, hospitalization and long COVID) are of low \nquality. At best, the additional protection provided by a seasonal \nbooster is moderate and of short duration. \nACIP Meeting, CDC\nSeptember 19, 2025Recommended Updates to the Vaccine Information Statement\n2.There is evidence that repeated seasonal mRNA boosters cause \nacquired changes in the immune system and may be associated with \nincreased vulnerability to future infections, including SARS -CoV-2 and \nother respiratory viruses. These risks, as well as potential risks of autoimmunity, chronic inflammation, immune tolerance and impaired \nimmune surveillance including immune fatigue or suppression, are \ncurrently not well understood. \nACIP Meeting, CDC\nSeptember 19, 2025Recommended Updates to the Vaccine Information Statement\n3.There are documented deaths from symptomatic and subclinical \nmyocarditis, pericarditis and potentially other cardiovascular conditions \npost COVID -19 vaccination, including of healthy children, with probable \ncausal relationship to the mRNA vaccines. This risk is likely relatively small but currently not well understood. \nACIP Meeting, CDC\nSeptember 19, 2025Recommended Updates to the Vaccine Information Statement\n4.Clinical reports demonstrate that in some cases COVID -19 vaccines can \ncause prolonged and debilitating post vaccine syndrome (PVS).  The injuries \nassociated with PVS involve diverse symptoms and conditions, many overlapping with long COVID injuries. Some of the observed symptoms and conditions may include insomnia, chronic pain and fatigue, dysautonomia (e.g., POTS), immune dysregulation and deficiency, autoimmune disorders, severe neuropathy and other neurodegenerative conditions, cardiovascular and neurovascular injuries, and severe clotting. The frequency of PVS and related risk factors are currently not well understood.\nACIP Meeting, CDC\nSeptember 19, 2025Recommended Updates to the Vaccine Information Statement\n5.There is evidence that in some individuals vaccinated with mRNA COVID -19 \nvaccines, the resulting spike protein, the mRNA and the nano- lipids \nformulation components persist in different body organs, including lymph \nnodes and the heart, for a prolonged period of months and possibly years in some patients. Prolonged and persistent exposure to spike, mRNA and nano- lipids particles is associated with post -vaccine syndrome (PVS) injuries \nas well as potentially other side effects that are currently only partially understood.\nACIP Meeting, CDC\nSeptember 19, 2025Recommended Updates to the Vaccine Information Statement\n6.The safety and the efficacy of COVID -19 vaccination during pregnancy have \nnever been tested in appropriately powered randomized clinical trials.  In \none randomized trial there was observed numerical imbalance of higher number of babies with congenital malformation among those born to vaccinated women. \nACIP Meeting, CDC\nSeptember 19, 2025Recommendations for 2025- 2026\nGuiding principles:\n•Access within the FDA authorized population\n•Benefits, risks and uncertainties must be communicated as part of proper informed \nconsent\n•Debated between Individual -based decisions to group recommendations", "summary": "ACIP Meeting, CDC September 19, 2025COVID -19 Vaccine Discussion  Framing, 2025-2026 Professor Retsef Levi, PhD, MIT ACIP Meeting, CDC September 19, 2025WG Main Takeaways •Assessments of the protection level provided by COVID -19 vaccines and especially  seasonal boosters against severe outcomes (hospitalization, ICU, death, long- covid)  are based on very low -quality data and analyses •Vaccine injuries are demonstrably not recognized by current pharmacovigilance  systems, leaving vaccine…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-september-18-19-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-09-18-19/10-levi-COVID-508.pdf", "doc_date": "2025-09-18", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 40}
{"title": "11 perlman bernstein miglis covid 508", "content": "Additional Workgroup \nConsiderations in COVID-19 \nVaccination Policy and Practice\nEvolution of a vaccine program. Chen RT, Orenstein WA. Epidemiologic methods in immunization programs. Epidemiol Rev. \n1996;18(2):102. Copyright © 1996 by the Oxford University Press.\nEdwards K, Hackell  J, Committee on Infectious Diseases, Committee on Practice and Ambulatory Medicine \nPediatrics  Sep 2016, 138 (3) e20162146; DOI: 10.1542/peds.2016- 2146Simple, stable recommendations \ncan increase vaccine coverage\nVAERS does not identify causality; rather it is a signal detection tool\n•Vaccination provided additional protection against COVID -19-associated: \nER and UC visits among children; protection generally similar across \nage groups \nER and UC visits and hospitalizations compared to no vaccine dose \namong adults \ncritical illness among older adults; protection appeared to be more \ndurable against critical illness compared to less severe outcomes\n•VE should be interpreted as the added benefit of COVID -19 vaccination in \na population with high levels of infection- induced immunity, vaccine-\ninduced immunity, or both Effectiveness of COVID -19 vaccination\nEthicsScience\nImplementationThree Pillars of the ACIP: \nScience and Much More\nLee G, Bell B, Romero J. The Advisory Committee on Immunization Practices and \nIts Role in the Pandemic Vaccine Response. JAMA Published Online J uly 22, \n2020. doi:10.1001/jama.2020.13167 \n•Healthcare providers always discuss vaccination pros/cons with patients.\n•In principle, clear recommendations and SCDM reach the same goal.\n•With routine, age - or risk -based recommendations, the default \ndecision is to vaccinate all patients that consent\n•However, recommendations with SCDM are perceived differently.\nSCDM has no default – vaccination is often interpreted as optional\n•Plus, the need for a provider prescription creates an unnecessary step to \nreceiving a vaccine and does not effectively target those at high riskShared clinical decision -making (SCDM) \nand a need for provider prescription \ncreate barriers to COVID -19 vaccination\n25%\n17% 18%39%2023 CHILD POPULATION BY AGE GROUP IN US\n(CHILDREN < 5 MORE LIKELY TO BE INFECTION NAÏVE)\nData from the U.S. Census Bureau, Population Division\nAnnie E. Casey Foundation tracks the well -being of children, youth, and families in US\n< 6 months\n6-23 months\nAntepartum Vaccination Protects \nNewborns and Young Infants\n\n“Immunosenescence” means older \npeople do not have as good an \nimmune response as when younger\n\nKey Messages for Consideration\n•The ACIP pillars are not driven by science alone; implementation \nand ethics are additional important considerations for vaccine accessibility\n•Simple, stable recommendations can increase vaccine coverage\n•COVID -19 vaccines are highly safe and effective\n•Shared clinical decision -making and the need for a provider \nprescription create unnecessary steps to receiving a vaccine \nand do not effectively target those at high risk\nKey Messages for Consideration\n•COVID -19 vaccination rates in the younger pediatric population \nare very low: the primary COVID -19 vaccination series is needed\n•Antepartum vaccination especially helps protect infection -naïve \nnewborns and young infants under 6 months of age\n•Older people do not make as good an immune response as \nwhen younger (“ Immunosenescence”)\n•COVID -19 vaccination matters for pregnant women, pediatric \npatients especially < 2 years of age, people 65 years and older, those of any age with a weakened immune system or chronic medical conditions, and anyone who feels they want \nprotection for themselves or their family !", "summary": "Additional Workgroup  Considerations in COVID-19  Vaccination Policy and Practice Evolution of a vaccine program. Chen RT, Orenstein WA. Epidemiologic methods in immunization programs. Epidemiol Rev.  1996;18(2):102. Copyright © 1996 by the Oxford University Press. Edwards K, Hackell  J, Committee on Infectious Diseases, Committee on Practice and Ambulatory Medicine  Pediatrics  Sep 2016, 138 (3) e20162146; DOI: 10.1542/peds.2016- 2146Simple, stable recommendations  can increase vaccine…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-september-18-19-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-09-18-19/11-perlman-bernstein-miglis-covid-508.pdf", "doc_date": "2025-09-18", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 20}
{"title": "01 MacNeil COVID 508", "content": "Advisory Committee on Immunization Practices\nCOVID -19 Session\nCoronavirus and Other Respiratory Viruses Division\nJune 25, 2025National Center for Immunization and Respiratory Diseases\n1\n Introduction  Dr. Adam MacNeil (CDC/NCIRD)\nCOVID -19 epidemiology Dr. Adam MacNeil (CDC/NCIRD)\nCOVID -19 vaccine effectiveness update Dr. Adam MacNeil (CDC/NCIRD)\nCOVID -19 vaccine safety update Dr. Sarah Meyer (CDC/NCEZID)\nCOVID -19 vaccine coverage and \nimplementation Dr. Georgina Peacock (CDC/NCIRD)\nEvidence to recommendations (partial) Dr. Adam MacNeil (CDC/NCIRD)Agenda COVID -19 session: June 25, 2025\n•June 2024: ACIP recommended 2024 –2025 COVID -19 vaccination for all people ages 6 months and older (published in \nSeptember 2024 MMWR1).\n•August 2024: FDA approved or authorized the Novavax, Moderna, and Pfizer -BioNTech 2024 –2025 COVID -19 vaccines.\n•October 2024: ACIP recommended additional doses for adults ages 65 years and older and people ages 6 months and \nolder with moderate or severe immunocompromise (published December 2024 MMWR2).\n•August, September, October 2024: The Interim Clinical Considerations for Use of COVID -19 vaccines was updated with \ndetailed guidance.3\n•May 2025: \n-Per HHS directive, CDC updated COVID -19 vaccine recommendations to shared clinical decision -making for healthy \nchildren ages 6 months –17 years and no guidance/not applicable for pregnant women.\n-FDA approved Novavax’s NUVAXOVID (2024 –2025 Formula) and Moderna’s MNEXSPIKE (2024 –2025 Formula) for \npeople ages 12 –64 years at high risk for severe COVID -19 and all adults ages 65 years and older.  \n-FDA’s Vaccines and Related Biological Products Advisory Committee met to discuss strain selection for the 2025 –\n2026 COVID -19 vaccines. FDA advised manufacturers that 2025 –2026 Formula COVID -19 vaccines should be \nmonovalent JN.1 -lineage -based, preferentially using the LP .8.1 strain.4Federal COVID -19 vaccine updates, June 2024 –May 2025\n1. Panagiotakopoulos L, et al. Use of COVID -19 Vaccines for Persons Aged ≥6 Months: Recommendations of the Advisory Committee on Im munization Practices — United States, 2024 –2025. MMWR Morb  Mortal Wkly  Rep 2024;73:819 –824. DOI: \n10.15585/mmwr.mm7337e2 .\n2. Roper LE, et al. Use of Additional Doses of 2024 –2025 COVID -19 Vaccine for Adults Aged ≥65 Years and Persons Aged ≥6 Months with  Moderate or Severe Immunocompromise: Recommendations of the Advisory Committee on Immunization \nPractices — United States, 2024. MMWR Morb  Mortal Wkly  Rep 2024;73:1118 –1123. DOI: 10.15585/mmwr.mm7349a2 .\n3. https://www.cdc.gov/covid/hcp/vaccine -considerations/index.html  \n4. https://www.fda.gov/vaccines -blood -biologics/industry -biologics/covid -19-vaccines -2025 -2026 -formula -use-united -states -beginning -fall-2025  \nACIP: Advisory Committee on Immunization Practices | FDA: Food and Drug Administration | MMWR: Morbidity and Mortality Weekly  Report3\n•Children ages 6 months –4 years\n-Unvaccinated: May receive a multidose initial series with a 2024 –2025 mRNA vaccine using shared \nclinical decision -making \n-Previously completed an initial series: May receive 1 dose of a 2024 –2025 mRNA vaccine from the same \nmanufacturer as the initial series using shared clinical decision -making\n•People ages 5 –17 years: \n-May receive 1 dose of an age -appropriate 2024 –2025 COVID -19 vaccine using shared clinical decision -\nmaking \n•Adults ages 18 –64 years:\n-Should receive 1 dose of any 2024 –2025 COVID -19 vaccine\n•Adults ages 65 years and older: \n-Should receive 2 doses of any 2024 –2025 COVID -19 vaccine, spaced 6 months apart (minimum interval 2 \nmonths)Overview of the current COVID -19 vaccination schedule: \nRoutine vaccination\nhttps://www.cdc.gov/covid/hcp/vaccine -considerations/routine -guidance.html  4\n•Unvaccinated: \n-Should receive a multidose initial vaccination series with an age -appropriate \n2024 –2025 vaccine and receive 1 dose of 2024 –2025 vaccine 6 months after \ncompleting the initial series (minimum interval 2 months)\n•Previously completed an initial series: \n-Should receive 2 doses of an age -appropriate 2024 –2025 COVID -19 vaccine, \nspaced 6 months apart (minimum interval 2 months) \n•May receive additional age -appropriate 2024 –2025 COVID -19 vaccine \ndoses under shared clinical decision -making (minimum interval 2 \nmonths) Overview of the current COVID -19 vaccination schedule: \nModerate or severe immunocompromise\n5 https://www.cdc.gov/covid/hcp/vaccine -considerations/immunocompromised.html  \nSeptember 20231June 20242April 20253June 2025Previous Work Group considerations of COVID -19 vaccine \nnon-universal recommendations\n1 September 12, 2023. ACIP presentation, slide 124. https://www.cdc.gov/acip/downloads/slides -2023 -09-12/11 -COVID -Wallace -508.pdf  \n2 June 27, 2024. ACIP presentation, slide 83. https://www.cdc.gov/acip/downloads/slides -2024 -06-26-28/06 -COVID -Panagiotakopoulos -508.pdf\n3 April 15, 2025. ACIP presentation, slide 65. https://www.cdc.gov/acip/downloads/slides -2025 -04-15-16/05 -Panagiotakopoulos -COVID -508.pdf  \n 6\n•Age-appropriate 2025 –2026 COVID -19 vaccines* for all infants and children \nages 6–23 months\n•Age-appropriate 2025 –2026 COVID -19 vaccine for persons ages 2–64 years ​ for \nthe following groups:\n•Persons at high risk of severe COVID -19​, including p regnant women (for infant and maternal \nprotection)\n•Persons at high risk of exposure to SARS -CoV-2\n•Shared clinical decision -making for persons desiring additional protection from COVID -19​\n•2 doses of 2025 –2026 COVID -19 vaccine for all adults ages ≥65 years and \npersons ages ≥6 months with moderate or severe immunocompromise **Summary of recent COVID -19 Work Group discussions\n*Number of doses depends on age, vaccine manufacturer, and vaccine history.\n** Persons with immunocompromise who are unvaccinated or did not complete an initial series with 2024 -2025 vaccine should comple te the initial series followed by 1 dose of \n2025 -2026 vaccine 6 months after the initial series. 7", "summary": "Advisory Committee on Immunization Practices COVID -19 Session Coronavirus and Other Respiratory Viruses Division June 25, 2025National Center for Immunization and Respiratory Diseases 1  Introduction  Dr. Adam MacNeil (CDC/NCIRD) COVID -19 epidemiology Dr. Adam MacNeil (CDC/NCIRD) COVID -19 vaccine effectiveness update Dr. Adam MacNeil (CDC/NCIRD) COVID -19 vaccine safety update Dr. Sarah Meyer (CDC/NCEZID) COVID -19 vaccine coverage and  implementation Dr. Georgina Peacock (CDC/NCIRD)…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-25-26-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-06-25-26/01-MacNeil-COVID-508.pdf", "doc_date": "2025-06-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 7}
{"title": "02 MacNeil COVID 508", "content": "Current Epidemiology of COVID -19 \nCoronavirus and Other Respiratory Viruses Division\nAdvisory Committee on Immunization Practices (ACIP)\nJune 25, 2025National Center for Immunization and Respiratory Diseases\n1\nCOVID- 19 continues to impact Americans’ health.\n* Based on data from September 29, 2024 through June 7, 2025.\nSource: https://www.cdc.gov/covid/php/surveillance/burden- estimates.html  2\n\nAmong adults aged ≥18 years, 3.6%  \nreported Long COVID \nsymptoms, and 8.4% reported ever \nhaving Long COVID1\nMore than 3 in 5 adults with Long \nCOVID reported activity limitations1\nAmong children aged 0 -17 \nyears, 0.4% reported Long COVID \nsymptoms, and 1.4% reported ever \nhaving Long COVID2Long COVID is a significant public health threat.\n1.Vahratian , et al . Prevalence of Post –COVID -19 Condition and Activity -Limiting Post –COVID -19 Condition Among Adults. doi:10.1001/jamanetworkopen.2024.51151\n2.Ford, et al. Long COVID Prevalence and Associated Activity Limitation in US Children. doi:10.1001/jamapediatrics.2024.6206National surveys in 2023 estimated approximately 9.2 million adults and 0.3 million \nchildren in the U.S. had Long COVID.\n  \nAlmost 4 in 5 children with Long \nCOVID reported activity limitations2\n3\nCOVID- NET is a population -based hospitalization \nsurveillance platform.\n•RESP -NET includes COVID -NET, RSV -NET, FluSurv -NET\n•>300 acute -care hospitals\n•185 counties in 13 states (population- based rates)\n•~10% of the U.S. population\n•Positive SARS -CoV-2 test ≤14 days before admission or during hospitalization\n•Screening or clinician -driven testing\n•Clinical data: age - and site -stratified random sample of hospitalized patients\n•Seasons defined in this presentation as July –June for rates.\n-Most recent 12 months of sampled data\nCOVID -NET: https://www.cdc.gov/covid/php/covid- net/index.html   Some slides display data from 90 counties in 12 states due to incomplete data.4\n\n010203040\n20\n2020\n21202220\n2320242025Rates of COVID -19, influenza, and RSV hospitalization — RESP -NET, 2020– 2025\n2020 2021 2022 2023 2024 2025Weekly COVID- 19-associated hospitalization rates have \npeaked in both winter and summer.\n50246810121416Hospitalizations per 100,000 population\nMonth and YearWeekly Rates of COVID -19–, Influenza -, and RSV -Associated \nHospitalizations — RESP- NET, July 2023– April 2025\nCOVID-19 Influenza RSV\nFigures displays weekly Rates of COVID -19–, Influenza -, and RSV -Associated Hospitalizations — RESP -NET, July 2023 –May 2025.\nRates for all three pathogens (COVID -19, influenza, and respiratory syncytial virus [RSV]) are laboratory -confirmed. Data source : https://www.cdc.gov/resp -net/dashboard/  \nNote that rates are not adjusted for testing. Rates are not limited to admissions where the respiratory infection is the like ly primary reason for admission. \nCumulative COVID- 19–associated hospitalization rates for the \nJuly 2024–May 2025 period were higher during summer and fall \n2024 and lower during the winter months compared to July \n2023–June 2024.\n6020406080100120140160180200\nJul Aug Sep Oct Nov Dec Jan Feb Mar Apr May JuneHospitalizations per 100,000 population\nMonthCumulative Rates of COVID -19–, Influenza- , and RSV -Associated Hospitalizations, by Surveillance Season* —\nRESP- NET, July 2023– May 2025\nCOVID 2023– 2024 Influenza 2023– 2024 RSV 2023– 2024\nCOVID 2024– 2025 Influenza 2024– 2025 RSV 2024– 2025\n* Seasons are defined as July through June. The 2024 –2025 season shows data from July 2024– May 2025 and is ongoing. Influenza surveillance is conducted October – April. \nRates for all three pathogens (SARS- CoV-2, influenza, and respiratory syncytial virus [RSV]) are laboratory -confirmed. Data sour ce: https://www.cdc.gov/resp -net/dashboard/  \nNote that rates are not adjusted for testing. Rates are not limited to admissions where the respiratory infection is the like ly primary reason for admission. \nFrom July 2024 – April 2025, a period that included a high \nseverity influenza season1, more infants <1 and adults ≥75 had \nhospitalizations associated with COVID -19 than influenza.\n701002003004005006007008009001000\n<1 1–4 5–11 12–17 18–49 50–64 65–74 ≥75Hospitalizations per 100,000 population\nAge group (years)Cumulative hospitalization rates of laboratory -confirmed COVID-19 and influenza hospitalizations —\nRESP-NET, July 2024–April 2025\nCOVID-19 Influenza\nCumulative hospitalization rates with laboratory -confirmed SARS -CoV-2 and influenza hospitalizations — RESP -NET, July 2024 –April  2025. Note that influenza surveillance is conducted \nfrom October –April annually. Data source: https://www.cdc.gov/resp -net/dashboard/ . Note that rates are not adjusted for testing nor limited to admissions where the respiratory \ninfection is the likely primary reason for admission.  1https://www.cdc.gov/flu/php/surveillance/in- season -severity.html\nCumulative COVID- 19-associated hospitalization rates are highest \namong adults aged ≥75 years, followed by adults aged 65–74 years \nand infants aged <6 months.\nWeekly rates of COVID -19–associated hospitalizations per 100,000 population by age group— COVID- NET, July 2024– May 2025\nNote that rates are not adjusted for testing. Rates are not limited to admissions where the respiratory infection is the like ly primary reason for admission. 8050100150200250300\nJul 2024 Aug 2024 Sep 2024 Oct 2024 Nov 2024 Dec 2024 Jan 2025 Feb 2025 Mar 2025 Apr 2025 May 2025Rate per 100,000 population\nSurveillance week end date\n<6 months 6–23 months 2–4 years 5–11 years\n12–17 years 18–49 years 50–64 years 65–74 years50–64 years: 101\n18–49 years: 36\n2–4 years:  22\n12–17 years: 12\n5–11 years: 10<6 months: 268\n65–74 years: 266\n50–64 years: 103\n6–23 months: 10002505007501000Rate per 100,000≥75 years: 884\nCOVID -19 Mortality\n9\nWeekly number of COVID- 19-associated deaths reported \nto CDC, United States, June 8, 2024 –  June 7, 2025\nThe most recent 3 weeks of mortality counts are shaded grey because NVSS reporting is  <95% during this period.\nProvisional data are non -final counts of deaths based on reported mortality data in NVSS. Deaths include those with COVID- 19, coded as ICD– 10 code U07.1, on the death certificate. \nDeath data are displayed by date of death (event). Data include underlying and contributing causes of death.CDC COVID Data Tracker. National Center for Health Statistics (NCHS) National Vital Statistics System (NVSS). \nhttps://covid.cdc.gov/covid- data -tracker/#trends_weeklydeaths_select_00  \nAccessed June 18, 202502004006008001,0001,2001,4001,600\n6/8/2024 8/8/2024 10/8/2024 12/8/2024 2/8/2025 4/8/2025Weekly Deaths\n10\nTotal number of deaths with COVID -19listed as the underlying \ncause1,2 in July 2024–June 2025, by age group, United States \n1. Provisional data \n2. Underlying cause of death Source: Centers for Disease Control and Prevention, National Center for Health Statistics. Natio nal Vital Statistics System, Provisional Mortality on CDC \nWONDER Online Database. Data are from the final Underlying Cause of Death Files, provisional data for  2024 and provisional and partial data from 2025 , as compiled from data provided \nby the 57 vital statistics jurisdictions through the Vital Statistics Cooperative Program. Number of deaths includes COVID- 19 code (U07.1) as the underlying cause of death. \nhttp://wonder.cdc.gov/mcd -icd10 -provisional.html, accessed June 20 , 2025 45 16 294761,7684,00916,375 \n020004000600080001000012000140001600018000\n<2 years 2-4 years 5-17 years 18-49 years 50-64 years 65-74 years ≥75 yearsNumber of Deaths\n1\n11\nDeath certificate data likely underestimate COVID -19-associated \ndeaths.\nFigure displays the weighted percentage of COVID -19-associated hospitalizations with COVID -19 listed as an underlying or contributing cause of death,* by surveillance period** — COVID -NET, March 2020–\nSeptember 2023\n* COVID -19 as a cause of death was defined as the inclusion of International Classification of Diseases, Tenth Edition (ICD- 10) code U07.1 on the death certificate as an underlying or contributing cause of death.\n**Surveillance periods are defined as October –September, except for 2020, which was defined as March 2020– September 2020. \n12Among in- hospital \ndeaths in patients \nwith laboratory -\nconfirmed SARS -\nCoV- 2, the proportion \nwith a COVID- 19 \ncause of death listed decreased from 95% \nin 2020 to 60% in \n2022– 2023.95\n89\n77\n60\n0102030405060708090100\nCategory 1Percent of in -hospital deaths with COVID -\n19 cause of death on the death certificate\n2020 2020 –2021 2021 –2022 2022 –2023\nCOVID -19 continues to contribute to a large number of deaths in \nthe United States.\n* COVID -19 as a cause of death was defined as the inclusion of International Classification of Diseases, Tenth Edition (ICD- 10) code U07.1 on the death certificate (October 2024- May 2025) as underlying or \ncontributing cause of death. Provisional death certificate data from the National Center for Health statistics \n† Based on data from September 29, 2024 through June 7, 2025. Source: https://www.cdc.gov/covid/php/surveillance/burden- estimates.html . Accessed June 20, 2025\n13Data sourceEstimated COVID -19 \ndeaths since October \n2024\nDeath certificate data* 20,800 \nModeled estimates based on \nmultiple data sources†32,000– 51,000\n\nPediatric COVID -19–Associated \nHospitalizations\n14\nThe highest rates for COVID- 19 in the New Vaccine Surveillance \nNetwork were observed in infants <6 months of age.\nPediatric COVID- 19 and influenza hospitalization rates among children <18 years, New Vaccine Surveillance Network (NVSN), July 2024-  March 2025. Rate estimates with standard error >30 due to few \ndetections are not presented. Annual rates presented July – June of each season, with exception of 2024 -2025, which represents J uly 2024 – March 2025.\nNVSN, unpublished data209.8\n83.0\n17.07.4149.4\n82.9\n58.5\n39.6\n11.1\n0100200300\n<6m 6-23m 2-4y 5-11y 12-17yHospitalization rate , No./100000 children\nAgeSARS-CoV-2\nInfluenza\n15\nMore than half of pediatric COVID- 19-associated \nhospitalizations occur in children aged <2 years.\n160%10%20%30%40%50%60%70%80%90%100%Percent of COVID -19–associated hospitalizations\nSurveillance week end datePercent of weekly COVID -19–associated hospitalizations among children and adolescents, by age group \n—\nCOVID -NET, July 2024– April 2025\n<6 months 6–23 months 2–4 years 5–11 years 12–17 years\nFigure displays percent of weekly COVID -19–associated hospitalizations among children and adolescents, by age group — COVID -NET,  July 2024– May 2025.≤6 months = 27%6–23 months = 30%\n<2 years = 57%2–17 years = 43%\nCOVID- 19 causes severe disease in infants ages <6 months.\nData reported from July 2024– May 2025. Excludes newborns who were admitted during the same hospitalizations as their birth. Note  that rates are not adjusted for testing. Rates are not \nlimited to admissions where the respiratory infection is the likely primary reason for admission. •Highest rate of COVID -19-\nassociated hospitalization \namong all pediatric age groups\n-Rates comparable to adults ages \n65–74 years\n050100150200250300\nJul\n2024Aug\n2024Sep\n2024Oct\n2024Nov\n2024Dec\n2024Jan\n2025Feb\n2025Mar\n2025Apr\n2025May\n2025Rate per 100,000 population\nSurveillance week end dateCumulative rates of COVID -19–associated hospitalizations among \nchildren and adolescents ages <18 years —\nCOVID -NET, July 2024– May 2025\n<6 months 6–23 months 2–4 years\n5–11 years 12–17 years 50–64 years\n65–74 yearsCumulative rate per 100,000: \n<6 months: 268\n65–74 years: 266\n17\nInfants <6 months experience high rates of severe COVID-\n19 disease.\n18No COVID -19 vaccine products are approved for infants ages <6 months.\nAny protection must come from transfer of maternal antibodies, either from \nvaccination during pregnancy or prior infectionAmong infants <6 months hospitalized recently for COVID -19:\n22% were admitted to the ICU\n71% had no underlying medical conditions\n3.5% had any record of maternal COVID -19 vaccination during pregnancy\nData reported from April 2024 –March 2025. Hospitalizations are limited to those with COVID -19 as the likely reason for admission . Excludes newborns who were admitted during the \nsame hospitalizations as their birth.\n190%10%20%30%40%50%60%70%80%90%100%Percent of COVID -19–associated \nhospitalizations\nSurveillance week end datePercent of weekly COVID -19–associated hospitalizations among children and adolescents, by age group \n—\nCOVID -NET, October 2024– April 2025\n6–23 months 2–4 years 5–11 years 12–17 years\nFigure displays the percent of weekly COVID -19–associated hospitalizations among children and adolescents, by age group — COVID -NET, October 2024– May 2025.Among vaccine -eligible children and adolescents ages 6 \nmonths –17 years, 41% of COVID- 19-associated hospitalizations \noccurred among children ages 6–23 months.\nDuring July 2024– May \n2025:\n \n•6–23 months = 41%\n•2–4 years = 18%\n•5–11 years = 20%\n•12–17 years = 21%\nCOVID -19-associated cumulative hospitalization rates are \nhighest among the youngest age groups.\nNote that rates are not adjusted for testing. Rates are not limited to admissions where the respiratory infection is the like ly primary reason for admission. 20050100150200250300\nJul 2024 Aug 2024 Sep 2024 Oct 2024 Nov 2024 Dec 2024 Jan 2025 Feb 2025 Mar 2025 Apr 2025 May 2025Rate per 100,000 population\nSurveillance week end dateCumulative rates of COVID -19–associated hospitalizations among children and adolescents ages ≤17 years —\nCOVID -NET, July 2024– May 2025\n<6 months 6–23 months 2–4 years ≤4 years 5–11 years 12–17 years65–74 years: 258\n50–64 years: 101\n18–49 years: 36\n12–17 years: 12\n5–11 years: 10≤4 years: 68257Rates for 100K population, \nby age group:\n<6 months: 268\n6–23 months: 100\n2–4 years:  22\nThe youngest age groups have comparable rates of cumulative \nCOVID -19-associated hospitalization to some adult age groups, but \ndirect comparisons are challenging.\nNote that rates are not adjusted for testing. Rates are not limited to admissions where the respiratory infection is the like ly primary reason for admission. 21050100150200250300\nJul 2024 Aug 2024 Sep 2024 Oct 2024 Nov 2024 Dec 2024 Jan 2025 Feb 2025 Mar 2025 Apr 2025 May 2025Rate per 100,000 population\nSurveillance week end dateCumulative rates of COVID -19–associated hospitalizations among children and adolescents ages ≤17 years —\nCOVID -NET, July 2024– May 2025\n<6 months 6–23 months 2–4 years 5–11 years65–74 years: 258\n50–64 years: 101\n18–49 years: 36\n12–17 years: 12\n5–11 years: 10Rates for 100K population, \nby age group:\n<6 months: 268\n65–74 years: 266\n50–64 years: 103\n6–23 months: 100\n2–4 years:  22\nThe youngest age groups have comparable rates of cumulative \nCOVID -19-associated hospitalization to some adult age groups, but \ndirect comparisons are challenging.\nNote that rates are not adjusted for testing. Rates are not limited to admissions where the respiratory infection is the like ly primary reason for admission. 22050100150200250300\nJul 2024 Aug 2024 Sep 2024 Oct 2024 Nov 2024 Dec 2024 Jan 2025 Feb 2025 Mar 2025 Apr 2025 May 2025Rate per 100,000 population\nSurveillance week end dateCumulative rates of COVID -19–associated hospitalizations among children and adolescents ages ≤17 years —\nCOVID -NET, July 2024– May 2025\n<6 months 6–23 months 2–4 years 5–11 years65–74 years: 258\n50–64 years: 101\n18–49 years: 36\n12–17 years: 12\n5–11 years: 10Rates for 100K population, \nby age group:\n<6 months: 268\n65–74 years: 266\n50–64 years: 103\n6–23 months: 100\n2–4 years:  22% with ≥1 underlying medical conditions \namong those hospitalized for COVID -19:  \nAdults aged 50 -64: 94%\nInfants and children 6 -23 months: 46%\nProportion of children hospitalized for COVID- 19 who \nhad no underlying medical conditions\nFigure displays the weighted percent of children and adolescents hospitalized for COVID -19 with no underlying medical conditions, by age group —  COVID -NET, April 2024 –March 2025.  \nHospitalizations are limited to those with COVID -19 as the presenting complaint upon admission. Pregnant adolescents ages 15 –17 years are excluded from proportions \npresented. 2371\n54\n29\n24 23\n01020304050607080\n<6 months 6–23 months 2–4 years 5–11 years 12–17 yearsPercentage of pediatric patients hospitalized \nwho have no underlying medical conditions\nAge Group<2 years\n2–17 yearsMost hospitalized \nchildren ages <2 \nyears did not have \nany underlying \nmedical condition.\nPercent of children and adolescents for COVID -19 who were admitted to the ICU, by age group — COVID -NET, April 2024 –March 2025\nHospitalizations are limited to those with COVID -19 as the likely reason for admission. Pregnant adolescents ages 15 –17 years are excluded from proportions presented. 2225\n2128\n26\n051015202530\n<6 months 6–23 months 2–4 years 5–11 years 12–17 yearsPercent of pediatric  hospitalizations \nrequiring ICU admission\nAge group~1 in 4 children ages <18 years in all age groups \nhospitalized for COVID- 19 required ICU admission.\n2424%\nPercent of children and adolescents for COVID -19 who were admitted to the ICU, by age group — COVID -NET, April 2024 –March 2025\nHospitalizations are limited to those with COVID -19 as the likely reason for admission. Pregnant adolescents ages 15 –17 years are excluded from proportions presented. 2225\n2128\n26\n051015202530\n<6 months 6–23 months 2–4 years 5–11 years 12–17 yearsPercent of pediatric  hospitalizations \nrequiring ICU admission\nAge groupAmong children <2 \nyears admitted to \nICU, most (53%) did \nnot have underlying \nmedical conditions.\n25~1 in 4 children ages <18 years in all age groups \nhospitalized for COVID- 19 required ICU admission.\n23%\n89% of COVID -19 vaccine-eligible children and adolescents who were \nhospitalized with COVID -19 had no record of receiving the most recently \nrecommended COVID -19 vaccines.\nNo record of COVID -19 vaccine since July 1, 2023: No recorded doses of any COVID -19 vaccine dose since July 1, 2023. ≥1 vaccine dose since July 1, 2023, but \nno 2024– 2025 dose:  Received at least one COVID -19 vaccination since July 1, 2023, but no record of receiving 2024- 2025 vaccine dose. Receipt of ≥1 24- 25 formula \ndose: Received at least 1 dose of the 2024- 2025 vaccine dose. Persons with unknown vaccination status (6.4%) are excluded. Hospitaliza tions are limited to those with \nCOVID -19 as the presenting complaint upon admission.908589 89\n1 2 311013\n810\n0102030405060708090100\n6 months –4 years 5–11 years 12–17 years 6 months –17 yearsWeighted percent of hospitalizationsVaccination status among children and adolescents with COVID-19 –associated hospitalizations,\nby age group — COVID -NET, October 2024 –March 2025\nNo record of COVID-19 vaccine since July 1, 2023\n≥1 vaccine dose since July 1, 2023, but no record of receiving 24- 25 formula dose\nReceipt of ≥1 24- 25 formula dose\n26\nPediatric COVID -19 mortality\n27\nTotal number of COVID -19- and Influenza -associated \ndeaths1,2, among ages 0 –17 years in July 2024 –June 2025, \nUnited States\n45\n162944 42142\n020406080100120140160\n<2 year 2–4 years 5–17 yearsNumber of Deaths\nCOVID-19 Influenza\n1. Provisional data \n2. Underlying cause of death Source: Centers for Disease Control and Prevention, National Center for Health Statistics. National Vital Statistics System, Provisional Mortality on CDC WONDER Online \nDatabase. Data are from the final Underlying Cause of Death Files, provisional data for 2024 and provisional and partial data from 2025 , as compiled from data provided by the 57 vital statistics jurisdictions \nthrough the Vital Statistics Cooperative Program. Number of deaths includes influenza codes (J09 -J11) or COVID -19 code (U07.1) as the underlying cause of death. http://wonder.cdc.gov/mcd -icd10 -\nprovisional.html , accessed June 20, 2025 \nNote: Estimates of pediatric influenza deaths reported to CDC can be found here: https://www.cdc.gov/fluview/surveillance/2025 -week -15.html . Estimates will vary due to differences in reporting methods \nand timeframes used. 28\nDeaths among children with COVID- 19-associated \nhospitalizations within COVID- NET catchment area\n29Since March \n2020July 2022–\nJune 2023July 2023–\nMarch 2025\nIn-hospital and out- of-hospital deaths 128 32 25 (including 10* \nsince April 2024)\n•Among 25 pediatric deaths since July 2023:\n•13 (52%) were aged <2 years:  9 aged <6 months; 4 aged 6 –23 months\n•18 (72%) had ≥1 underlying medical condition\n•Of the 16 who were age- eligible for COVID -19 vaccination, 14 had no record of COVID -19 vaccination \nand none were up to date.\n•Death certificate data alone may underestimate COVID -19-associated pediatric deaths\n-Among the 25 deaths** for whom we have death certificate data with ICD -10 codes, 7 (28%) had COVID -19 listed \nas a cause of death (COD)\n-Additional 9 (36%) had CODs related to other respiratory or circulatory causesCOVID -NET \nrepresents 10% of \nthe U.S. population\n* In-hospital deaths only; complete death certificate data not yet available.\n** Deaths occurred during July 2022 and August 2023.\nSummary\nCOVID -19 Epidemiology in Infants, Children, and Adolescents\n30\nSummary of COVID- 19 Epidemiology for Infants, Children, and \nAdolescents\n•Most (57%) pediatric hospitalizations occur in children ages <2 years .\n-Most hospitalized children in these age groups have no underlying medical conditions, including 71% \nof infants ages <6 months and 54% of children ages 6 –23 months.\n•Rates of COVID -19–associated hospitalizations are highest among infants ages <6 months,  followed by \nthose ages 6 –23 months.\n-Rates of COVID -19-associated hospitalizations among infants ages <6 months are comparable to rates \namong adults ages 65 –74 years\n-No COVID -19 vaccine products are approved for infants ages <6 months. Any protection must come \nfrom transfer of maternal antibodies, either through vaccination during pregnancy or prior infection\n•Outcomes among hospitalized children can be severe, with  1 in 4 admitted to ICU .\n-Deaths from COVID -19 continue to occur among infants and children; death certificate data might \nundercount these. \n•The majority (89%) of COVID -19 vaccine -eligible children and adolescents who were hospitalized with \nCOVID -19 had no record of receiving the most recently recommended COVID -19 vaccine.\n31\nCOVID -19–Associated Hospitalizations \nAmong Adults Ages ≥18 Years\n32\nAdults ages ≥65 years comprise more than 2/3 of all \nCOVID- 19–associated hospitalizations among adults.\nFigure displays the percent of weekly COVID -19–associated hospitalizations among adults ages ≥18 years, by age group — COVID -NET, March 2020– May 2025.\nDuring this same period of January 2024 through March 2025, children and adolescents ages 17 years and younger comprised 4.1%  of all COVID -19-associated hospitalizations. 330%10%20%30%40%50%60%70%80%90%100%Percent of adults hospitalized with COVID -19\nSurveillance week end datePercent of weekly COVID -19–associated hospitalizations among adults ages ≥18 years, by age group —\nCOVID -NET, March 2020– April 2025\n18–49 years 50–64 years 65–74 years ≥75 years≥75 years=50%\n≥65 years=72%\n50–64 years=16%\nMost adults hospitalized for COVID- 19 have ≥1 \nunderlying medical condition; a majority have ≥2.\n34Prevalence of underlying medical conditions among adults ages ≥18 years, by age group — COVID -NET, April 2024 –March 2025.\nPregnant women ages 18 –49 years are excluded from proportions presented. Data are limited to hospitalizations with COVID -19 as t he likely reason for admission.1486\n61\n694\n75\n397\n85\n298\n84\n0102030405060708090100\n0 conditions ≥1 condition ≥2 conditionsWeighted percent of hospitalizations\nUnderlying medical conditionsPrevalence of underlying medical conditions among adults ages ≥18 years, by age group —\nCOVID -NET, April 2024 –March 2025 \n18–49 years 50–64 years\nAmong adults hospitalized for COVID- 19, 15% were \nadmitted to the intensive care unit (ICU).\n3517 17\n14\n6 6\n4\n145\n02468101214161820\n18–49 years 50–64 years ≥65 yearsWeighted percent of hospitalizationsAge groupProportion of adults hospitalized with COVID -19 with interventions and outcomes,\nby age group — COVID -NET, April 2024 –March 2025\nICU admission Invasive mechical ventilation In-hospital death\nThe figure displays the proportion of adults hospitalized for COVID -19 with interventions and outcomes, by age group — COVID -NET, April 2024 –March 2025.\nData are limited to hospitalizations where COVID -19 is a likely primary reason for admission. Deaths do not include other COVID -19-related deaths that might occur after a patient is \ndischarged to hospice or deaths that occur soon after hospital discharge that could be attributable to COVID -19-related illness.  Pregnant women ages 18 –49 years are excluded from \nproportions presented. During this period, 85% of all adults hospitalized with COVID- 19 who died in -hospital were ages ≥65 years. \nMost adults hospitalized for COVID- 19 had received no \nCOVID -19 vaccine since July 2023.\nFigure displays the COVID- 19 vaccination status among adults hospitalized for COVID -19, by age group — COVID -NET, October 2024– March 2025.\nData are limited to hospitalizations where COVID -19 is a likely primary reason for admission. 3687\n746862 65\n2 1 1 1 11125313734\n122117\n0102030405060708090100\n18–49 50–64 65–74 ≥75 ≥65Weighted percent of hospitalizations Age group in yearsVaccination status among adults hospitalized with COVID -19, by age group —\nCOVID -NET, October 2024– March 2025\nNo record of vaccination since 7/1/2023\nRecord of ≥1 COVID dose since 7/1/2023, but no record of receiving the 24- 25 \nformula dose\nCOVID -19-Associated Hospitalizations \namong Pregnant Women\n37\nPregnant women with COVID- 19–associated \nhospitalizations, April 2024 –March 2025\n•Pregnancy status collected from \nhospitalized women ages 15 –49 \nyears\n•28.5% of women ages 15 –49 \nyears hospitalized with \nlaboratory- confirmed SARS-\nCoV- 2 infection were pregnant\n-50% of those had COVID -19-\nrelated signs or symptoms\nSource: COVID -NET, unpublished data.38\n\nPregnant women with COVID- 19–associated \nhospitalization, April 2024– March 2025\nAmong 131 hospitalized pregnant women with a laboratory- confirmed \nSARS -CoV- 2-positive test result and COVID -19-related signs or symptoms:\n•50% had no underlying conditions\n•68% were no longer pregnant at discharge, among whom:\n-83% had a healthy newborn, 11% had a pre -term infant, 1% had an ill infant, and \n5% had pregnancy loss*\n•92% have no record of vaccination since July 1, 2023\n-5.8% received recommended 2024- 25 COVID -19 vaccine dose**\n* Includes spontaneous miscarriage and abortion.\n** Vaccination might have occurred before the pregnancy period and is not necessarily indicative of maternal vaccination stat us.\nSource: COVID -NET, unpublished data.39\nSummary\nAdults\n40\nSummary of COVID- 19 Epidemiology for Adults\n•Rates of COVID -19– associated hospitalization are highest among oldest adult age groups\n-Adults aged ≥65 years comprise 72% of adult COVID -19– associated hospitalizations \n-Ages ≥75 years: 50% of adult hospitalizations \n•COVID -19-associated hospitalization rates have decreased over time, but cumulative rates among \nadults aged ≥75 years remain high\n•Risk of hospitalization with COVID -19 continues year -round, peaking in the winter and summer.\n•65% of adults ages ≥65 years hospitalized with COVID -19 had no record of receiving ≥1 dose of the \nrecommended 2024 -25 COVID -19 vaccine prior to hospitalization.\n•Most adults with COVID -19-associated hospitalization have ≥1 underlying condition.\n•Among SARS -CoV -2-positive pregnant women admitted during April 2024 –March 2025 with COVID -\n19-related symptoms on admission, half had no underlying conditions and most (92%) have no \nrecord of COVID -19 vaccination since July 1, 2023\n41\nGenomics\n42\nSubsampled SARS -CoV-2 sequences by lineage group, date of specimen collection, and number of \nspike protein amino acid differences relative to Wuhan -Hu-1 reference\nUnited States, January 1, 2021–March 29, 2025\n* LF.7 includes LF.7, LF.7.2.1, LF7.7.1, and LF7.7.2. \nSequences were subsampled (100 per month) for analysis from an initial dataset of >1 million sequences spanning January 1, 20 21–March 29, 2025. Only lineages circulating at >5% prevalence nationally during at least one 2 -week period are displayed. Sequences are reported to CDC through the National \nSARS -CoV-2 Strain Surveillance program, contract laboratories, public health laboratories, and other U.S. institutions.  Lineages were ordered by date of first appearance on CDC’s COVID data tracker ( https://covid.cdc.gov/covid -data -tracker/#variant -proportions ). Lineages with identical spike receptor binding \ndomain amino acid sequences (residues 332 to 527) were grouped with a representative lineage and denoted as “representative l ineage-like.” Vaccine availability for a given composition was defined by the estimated date of earliest possible administration.Vaccine strain composition : original Bivalent (original, BA.4/5) XBB.1.5 JN.1/KP.2\nVariant\n43\nIn winter 2023-2024, we observed a strain replacement \nof XBB.1.5 -like viruses to JN.1- like viruses.\nJN.1-likeHV.1FL.1.5.1 -\nlikeEG.5 -likeXBB.1.5 -\nlike\nGenomic Surveillance for SARS -CoV -2 Variants: Circulation of Omicron XBB and JN.1 Lineages — United \nStates, May 2023– September 2024 | MMWR44\nWeighted SARS -CoV-2 Variant Proportion Estimates: XBB and JN.1 Lineages\nUnited States, October 1, 2023– March 29, 2025\n* LF.7 includes LF.7, LF.7.2.1, LF7.7.1, and LF7.7.2. \n† “Other” represents aggregated  lineages circulating at <1% prevalence nationally during all 2 -week periods displayed.\nLineages were ordered  by date of first appearance on CDC’s COVID data tracker ( https://covid.cdc.gov/covid- data -tracker/#variant- proportions ). Lineages with identical spike receptor binding domain amino acid sequences (residues 332 to 527) were \ngrouped with a representative lineage and denoted as “representative lineage -like.”†JN.1-likeKP.3.1.1-likeXEC\nLP.8.1LB.1-like\n45\nViruses that have predominated since January 2025 \nare all JN.1 descendants.\nCDC COVID Data Tracker: Variant Proportions\nWeighted and Nowcast Estimates in the United States \nfor 2 -week Periods, 2/16/2025 – 6/7/2025\nCDC COVID Data Tracker: Variant \nProportions\nAs of June 15, 2025Due to low numbers of sequences being reported to CDC, precision for the most recent reporting periods is low\n47\nConvergent Evolution of Different Omicron JN.1 Lineages\nKey changes in the spike receptor binding domain (RBD)* detected relative to KP.2\n* Lineages or lineage groups with ≥1% prevalence in at least one 2 -week period and substitutions present in ≥50% of sequences bel onging to a lineage were included. \n† The KP .2 spike protein sequence was used as a reference because of its inclusion in updated mRNA -based 2024– 2025 COVID -19 vaccin es. Substitutions compared to Wuhan- Hu-1 are \nunderlined.\n§ Indicates sites of independent substitution or deletion in at least two different evolutionary lineages. \nBolded sub- lineages are expanding in the United States as of June 7, 2025.Lineage N-terminal domain Receptor binding domain S2\n22 31 59 146 182 183 184 186 190 346 435 444 445 456 478 493 572 679 748 929 1086 1104 1235\nKP.2 \nReference\n† T S F H K Q G F R T A K H L T Q T K E S K L C\nKP.3 R E\nKP.3.1.1 ∆ R E\nKP.3.3 R E\nKP.2.3 ∆ Q I\nJN.1 R F V\nJN.1.16 Q R V\nJN.1.18.6 N S\nKP.2.15 ∆\nLB.1 ∆ H V\nLF.7 N P R S R I V\nLP.8.1 ∆ L S R E R\nMC.10.1 ∆ R S E\nMC.28.1 ∆ S E F\nXEC N S R E\nXEC.4 N S R E I\nXEK N S R E Q\nXFC N P R S R E R R\nNB.1.8.1 N S G S H I E\n48\nHuman sera collected after 2024- 2025 COVID -19 \nvaccination neutralizes LP.8.1 pseudoviruses and XEC \nvirus.\nMellis  et al. bioRxiv : Do Existing \nCOVID -19 Vaccines Need to Be \nUpdated in 2025?\nSuthar et al. The Lancet Infectious Diseases: The KP.2- adapted \nCOVID -19 vaccine improves neutralising activity against the XEC \nvariant -  ScienceDirect*Geometric mean titer (GMT)\n49\nAntigenic cartography with hamster and human sera \nindicate that JN.1 lineage viruses group together.\nWu-1 BA.2BA.5\nXBB.1.5\nJN.1KP.3.1.1ProVac\nHamster sera\nLive virus assay\n+0.5 log2 unit reactivity \nadjustment for the XEC \nantigen\nXEC LP.8.1 - H445R + L441I\nFrancis Crick Institute\nMRC University of Glasgow Centre for Virus Research\nCenter for Pathogen Evolution, University of Cambridge\n   Antigenic and Virological Characteristics of \nSARS -CoV-2 Variant BA.3.2, XFG, and \nNB.1.8.1\n•Current viruses are JN.1 descendants with 2 -3 substitutions in the spike receptor \nbinding domain in comparison to KP .2 spike\n•Current viruses are neutralized with sera from participants who received the 2024 -\n2025 COVID -19 vaccine\n•Antigenic cartography indicates JN.1 viruses are antigenically similar\n•FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) \nreviewed genomic and phenotypic data in May and voted unanimously to recommend a monovalent JN.1 -lineage vaccine composition. \n-FDA has advised manufacturers to use JN.1 -lineage based COVID -19 vaccines, preferentially \nusing the LP .8.1 strain, for the 2025- 2026 COVID -19 vaccinesSummary of COVID- 19 Genomics\nBack -up\nAmong all age groups, weekly rates of COVID -19–associated \nhospitalizations are highest among adults ages ≥75 years.\nFigure displays the w eekly rates of COVID -19–associated hospitalizations — COVID -NET, March 2020 –May 2025 .\nNote that rates are not adjusted for testing. Rates are not limited to admissions where the respiratory infection is the like ly primary reason for admission. 53010203040506070Rate per 100,000 population\nSurveillance week end dateWeekly rates of COVID -19–associated hospitalizations — COVID -NET, July 2023– April 2025\n<6 months 6–23 months 2–4 years 5–11 years 12–17 years\n18–49 years 50–64 years 65–74 years ≥75 years\nAmong all children and adolescents, rates of COVID -19-associated \nhospitalizations are highest among infants and children ages <2 years.\nFigure displays weekly rates of COVID -19–associated hospitalizations among children and adolescents ages ≤17 years — COVID -NET, July 2023– May 2025.\nNote that rates are not adjusted for testing. Rates are not limited to admissions where the respiratory infection is the like ly primary reason for admission. 540510152025\nJul\n2023Aug\n2023Sep\n2023Oct\n2023Nov\n2023Dec\n2023Jan\n2024Feb\n2024Mar\n2024Apr\n2024May\n2024Jun\n2024Jul\n2024Aug\n2024Sep\n2024Oct\n2024Nov\n2024Dec\n2024Jan\n2025Feb\n2025Mar\n2025Apr\n2025May\n2025Jun\n2025Hospitalizations per 100,000 population\nSurveillance periodWeekly rates of COVID -19–associated hospitalizations among children and adolescents ages ≤17 years — COVID -NET, July 2023–\nMay 2025\n<6 months 6–23 months 2–4 years\nStructure of XBB.1.5 vs. JN.1 spike\nBlue – NTD\nRed – RBD\nGreen – RBM\nPurple – S1\nGold – FCS\nBrown – S2Red sphere – deletions in one chain (labeled)\nMagenta sphere – substitutions in one chain (labeled)\nRaspberry sphere – deletions in rest 2 chains\nCyan sphere – substitutions in rest 2 chains\nSchrodinger homology model of JN.1, starting with 7YR2 (BA.2.75)\nPrepared by CDC: Megha Aggarwal, PhD 55\nLP.8.1, the lineage that predominated this spring, has \nlimited spike substitutions in comparison to KP.2\nRed sphere – deletions in one chain (labeled)\nMagenta sphere – substitutions in one chain (labeled)\nRaspberry sphere – deletions in rest 2 chains\nCyan sphere – substitutions in rest 2 chainsBlue – NTD\nRed – RBD\nGreen – RBM\nPurple – S1\nGold – FCS\nBrown – S2ACE-2\nStructure of JN.1 in complex with ACE -2 (PDB ID: 8YZE) Structure of JN.1 (PDB ID: 8Y5J)\n56\nCOVID- NET Summary\n•COVID -19 is estimated to have resulted in more than 250,000 hospitalizations since October 2024. \n•Among children, rates of COVID -19–associated hospitalizations are highest among children ages <2 years.\n-89% of children ages 6 months –17 years admitted for COVID -19 had no record of recent COVID -19 vaccination\n-1 in 5 children aged <2 years admitted for COVID -19 are admitted to the ICU\n•Of those ages <2 years admitted to the ICU, 53% had no underlying medical conditions\n•Among adults, rates of COVID -19–associated hospitalizations are highest among adults ages ≥75 years.\n•65% of adults ages ≥65 years hospitalized with COVID -19 had no record of receiving ≥1 dose of the \nrecommended 2024 -25 COVID -19 vaccine prior to hospitalization.\n•Most adults ages ≥18 years hospitalized for COVID -19 have ≥1 underlying medical condition.\n•Among SARS -CoV-2-positive pregnant women admitted during April 2024– March 2025 with COVID -19-\nrelated symptoms on admission​ \n-50% had no underlying medical condition​\n-92% have no record of COVID -19 vaccination since July 1, 2023​\n57\n~1 in 4 children and adolescents hospitalized for COVID- 19 are \nadmitted to the intensive care unit (ICU)\nHospitalizations are limited to those with COVID -19 as the presenting complaint upon admission. Pregnant adolescents ages 15 –17 years are excluded from proportions \npresented. 2225\n2128\n26\n051015202530\n<6 months 6 months –<2 \nyears2–4 years 5–11 years 12–17 yearsPercent of hospitalizationsPercent of children and adolescents with COVID-19 –\nassociated hospitalizations admitted to the ICU,\nby age group — COVID -NET, April 2024 –March 2025\nDuring this period, 7 children with COVID -19–associated \nhospitalization died in -hospital in the COVID -NET \ncatchment area. Age categoryAmong those \nadmitted to \nICU, % with no \nunderlying \nconditions\n<6 months 62%\n6–23 months 48%\n2–4 years 23%\n5–11 years 19%\n12–17 years 16%\nAmong children <2 years admitted to \nICU, most did not have underlying \nmedical conditions\n58", "summary": "Current Epidemiology of COVID -19  Coronavirus and Other Respiratory Viruses Division Advisory Committee on Immunization Practices (ACIP) June 25, 2025National Center for Immunization and Respiratory Diseases 1 COVID- 19 continues to impact Americans’ health. * Based on data from September 29, 2024 through June 7, 2025. Source: https://www.cdc.gov/covid/php/surveillance/burden- estimates.html  2  Among adults aged ≥18 years, 3.6%   reported Long COVID  symptoms, and 8.4% reported ever  having…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-25-26-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-06-25-26/02-MacNeil-COVID-508.pdf", "doc_date": "2025-06-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 58}
{"title": "03 MacNeil COVID 508", "content": "Updates to COVID -19 Vaccine Effectiveness\nCOVID -19 Session\nCoronavirus and Other Respiratory Viruses Division\nJune 25, 2025National Center for Immunization and Respiratory Diseases \n\n2•Vaccine effectiveness methods & context\n•Estimates of COVID -19 Vaccine Effectiveness in Children\n•Estimates of COVID -19 Vaccine Effectiveness in Adults\n•ConclusionsAgenda –COVID -19 vaccine effectiveness (VE)\nMethods & Context\n3\n4\nCase ControlPerson with acute\nrespiratory illness\nSARS -CoV-2 test\nCOVID -19 \nvaccination status\nFor respiratory viruses, CDC primarily uses case -control studies, including \nthe test -negative design (TND), to measure vaccine effectiveness (VE)\nEffectiveness = 1 – (odds ratio ) x 100%    Odds ratio = 𝑂𝑑𝑑𝑠  𝑜𝑓 𝑖𝑚𝑚𝑢𝑛𝑖𝑧𝑎𝑡𝑖𝑜𝑛 𝑐𝑎𝑠𝑒𝑠\n𝑂𝑑𝑑𝑠  𝑜𝑓 𝑖𝑚𝑚𝑢𝑛𝑖𝑧𝑎𝑡𝑖𝑜𝑛 𝑐𝑜𝑛𝑡𝑟𝑜𝑙𝑠\nVE findings should be interpreted as the \nadded benefit provided by COVID -19 \nvaccination in a population with a high \nprevalence of vaccine - and infection -induced \nimmunity.\n5VISION Multi -Site Network of Electronic Health Records\n>300 emergency departments and urgent cares clinics and >200 hospitals \n▪Design: Test-negative design\n▪Population: Persons visiting a participating emergency \ndepartment or urgent care or hospitalized with COVID -\n19-like illness with a SARS -CoV-2 NAAT test result \nwithin 10 days before or 72 hours after encounter\n−Cases : CLI with positive  NAAT or antigen for SARS -CoV-2 \nand no positive NAAT for RSV or influenza\n−Controls : CLI with negative  NAAT for SARS -CoV-2 and no \npositive NAAT for influenza (≥18 years) or RSV (≥60 years)\n▪Vaccination data: Documented by electronic health records and state and city registries\nCLI = COVID -19-like illness; ED/UC = emergency department/urgent care; RSV = respiratory syncytial virus; NAAT = nucleic acid am plification test\nCLI is defined based on the presence of specific discharge diagnosis codes. Additional methods available: Link -Gelles, et al. MM WR. \nhttps://www.cdc.gov/mmwr/volumes/74/wr/mm7406a1.htm    \n6\n•Case infants: hospitalized for COVID -19 as the primary reason \nfor admission and with a positive SARS -CoV-2 NAAT or antigen \ntest result\n•Control infants: hospitalized for COVID -19-like illness and \nnegative SARS -CoV-2 NAAT result, matched to case infants by \nsite; hospitalized within 4 weeks of case infant admissionOvercoming COVID -19 Network\n•Design: Case -control study to assess \neffectiveness of maternal vaccination \nagainst COVID -19-related hospitalizations in \ninfants <6 months of age\n•Population: 26 pediatric hospitals in 20 \nstates\n•Data collection: Baseline demographic and \nclinical characteristics obtained via chart \nabstraction and parent interview\n•Vaccination status: Maternal vaccination \nstatus verified using state vaccination \nregistries, electronic medical records, or \nother sources\n6\n7IVY Network —26 hospitals, 20 U.S. States\n•Design : Test-negative, case -control design\n•Population : Adults  ages  ≥18 years  hospitalized with COVID -19-\nlike illness* and SARS -CoV-2 test results within 10 days of \nillness onset and 3 days of admission\n–Cases: CLI and test  positive  for SARS -CoV-2 by NAAT or antigen\n–Controls : CLI and test negative  for SARS -CoV-2, influenza (≥18 \nyears) and RSV (≥60 years) by RT -PCR\n•Vaccination data: Electronic medical records, state and city \nregistries, and plausible self -report\n•Specimens: Nasal swabs  obtained on all patients for central \nRT-PCR testing and whole genome sequencing\n*COVID -19-like illness = CLI; CLI  is defined as presence of any one of the following: fever, cough, shortness of breath, chest imaging consistent with pneumoni a, or hypoxemia\nNAAT = nucleic acid amplification test\n\n8Measuring COVID -19 Vaccine Effectiveness (VE)\nMeasure Definition* Example \nvaccinated\ngroupExample comparison group\nAbsolute VE Compares frequency of health outcomes in \nvaccinated and unvaccinated people Received  original \nmonovalent doseReceived no COVID -19 vaccines ever\nRelative VE Compares frequency of health outcomes in \npeople who received one type of vaccine to \npeople who received a different vaccineReceived  bivalent \ndoseEligible for, but did not receive, \nbivalent COVID -19 vaccine , but \nreceived original monovalent dose\nVE of 2023 -2024  \nCOVID -19 vaccinesCompares people who received 2023 -2024  \nCOVID -19 vaccine to people who did not, \nregardless of past COVID -19 vaccinationReceived\n2023 -2024 doseEligible for, but did not receive, a \n2023 -2024 dose , regardless of past \nCOVID -19 vaccination history \nVE of 2024 -2025  \nCOVID -19 vaccinesCompares people who received 2024 -2025  \nCOVID -19 vaccine to people who did not, \nregardless of past COVID -19 vaccinationReceived\n2024 -2025 doseEligible for, but did not receive, a \n2024 -2025 dose , regardless of past \nCOVID -19 vaccination history \n* Prior SARS -CoV-2 infection is not generally considered, as it is documented inconsistently in medical records.\n9COVID -19 Vaccination Coverage Among Children and Adolescents 6 Months -17 \nYears, by Season and Age Group, National Immunization Survey, 2023 -2025\nWeekly estimates of COVID -19 vaccination coverage for vaccination among children through December 31, 2023, were calculated usin g data from the National Immunization Survey –Child COVID Module (NIS –\nCCM) . The NIS –CCM was discontinued at the end of 2023 and questions regarding COVID -19 vaccination status and intent were added to t heNational Immunization Survey –Flu (NIS–Flu).\nNIS–CCM and NIS –Flu are national random -digit dial cellular telephone surveys of households with children ages 6 months through 17 years; NIS –Flu is conducted during October -June. The respondent to a NIS –\nFlu survey is a parent or guardian who said they were knowledgeable about the child's vaccination history. All estimates are based upon parental report of receipt of vaccination and month of that vaccination. \nMore information : https://www.cdc.gov/covidvaxview/weekly -dashboard/child -coverage -vaccination.html  0%25%50%75%100%\nSep Oct Nov Dec Jan Feb Mar AprCOVID -19 vaccine coverage (%)\nMonth6 months-4 years, 2023-2024\n6 months-4 years, 2024-2025\n5-17 years, 2023-2024\n5-17 years, 2024-2025\n10COVID -19 Vaccination Coverage Among Adults ≥18 Years, 2023 -2024 and \n2024 -2025, NIS -ACM\nNational Immunization Survey -Adult COVID Module: Data from adults age ≥18 years are collected by telephone interview using a random -digit -dialed sample of cell telephone numbers  stratified by \nstate, the District of Columbia, five local jurisdictions (Bexar County TX, Chicago IL, Houston TX, New York City NY, and Phi ladelphia County PA), and Puerto Rico and the U.S. Virgin Islands. Data are \nweighted to represent the non -institutionalized U.S. population and mitigate possible bias that can result from an incomplete sa mple frame (exclusion of households with no phone service or only \nlandline telephones) or non -response. All responses are self -reported. For more information about the survey, see https://www.cd c.gov/nis/about/index.html.0%25%50%75%100%\nSept Week 1\nSept Week 2\nSept Week 3\nSept Week 4\nOct Week 1\nOct Week 2\nOct Week 3\nOct Week 4\nNov Week 1\nNov Week 2\nNov Week 3\nNov Week 4\nDec Week 1\nDec Week 2\nDec Week 3\nDec Week 4\nJan Week 1\nJan Week 2\nJan Week 3\nJan Week 4\nFeb Week 1\nFeb Week 2\nFeb Week 3\nFeb Week 4\nMar Week 1\nMar Week 2\nMar Week 3\nMar Week 4\nMar Week 5\nApr Week 1\nApr Week 2\nApr Week 3\nApr Week 4\nMay Week 1\nMay Week 2\nMay Week 3\nMay Week 4\nJun Week 1\nJun Week 2\nJun Week 3\nJun Week 4\nJun Week 5\nJul Week 1\nJul Week 2\nJul Week 3\nJuly Week 4\nAug Week 1\nAug Week 2\nAug Week 3COVID -19 Vaccination Coverage (%)\nWeek2023-2024 COVID-19 Vaccination Coverage 2024-2025 COVID-19 Vaccination Coverage\nMedicare fee -for-service beneficiaries aged ≥65 years were more likely to receive a \n2024 -2025 COVID -19 vaccine dose if they had an underlying medical condition  \nFee-for-Service:  enrolled in Medicare Parts A/B (and not Part C) for 365 days prior to reporting period. Estimates are based on  data released by Medicare claims data through January 2025; data may be incomplete \nafter December 7, 2024, due to 6 -week reporting lag. Data on uptake by season, race, and ethnicity can be accessed at: https://www.cdc.gov/covidvaxview/weekly -dashboard/adults -65yrs -older -vaccination.html . \nData on uptake by underlying medical condition from internal, unpublished analyses.32%29%\n28%\n24%\n0%25%50%75%100%\n08/25/24 -\n09/07/2409/08/24 -\n09/21/2409/22/24 -\n10/05/2410/06/24 -\n10/19/2410/20/24 -\n11/02/2411/03/24 -\n11/16/2411/17/24 -\n11/30/2412/01/24 -\n12/14/2412/15/24 -\n12/28/2412/29/24 -\n01/11/2501/12/25 -\n01/25/25% with ≥1 2024 -2025 COVID -19 vaccine dose\nTwo -week periodWeekly cumulative COVID -19 vaccination coverage, by underlying medical condition status,\nMedicare fee -for-service beneficiaries aged ≥65 years, August 2024 -January 2025\nAny immunocompromising condition\nAny underling medical condition\nOverall\nNo underlying medical condition\nEstimates of COVID -19 Vaccine \nEffectiveness in Children\n12\nCumulative rates of COVID -19 hospitalizations for the 2024 –\n2025 season are lower compared to 2023 -2024 season.\n13020406080100120\nJul Aug Sep Oct Nov Dec Jan Feb Mar Apr May JunHospitalizations per 100,000 \npopulation\nHospitalization monthCumulative Rates of COVID -19-Associated Hospitalizations among children and adolescents aged ≤17 years,\nby Surveillance Season* — COVID -NET, July 2023 –May 2025\n≤4 years, 2023 –2024 5–17 years, 2023 –2024\n≤4 years, 2024 –2025 5–17 years, 2024 –2025\n* Seasons are defined as July through June. The 2024 –2025 season shows data from July 2024 –April 2025 and is ongoing.\nData source: https://www.cdc.gov/resp -net/dashboard/  \nNote that rates are not adjusted for testing or limited to admissions where the respiratory infection is the likely primary r eason for admission. \n14Age group | COVID -19 vaccination statusTotal\nencountersSARS -CoV -2-\ntest -positive, N (%)Median interval since\nlast dose among\nthose vaccinated,\ndays (IQR) Adjusted vaccine effectiveness % (95% CI)\nNo updated 2023 -2024 COVID -19 vaccine dose*\n9 months -4 years 43,246 1,886 (4) 367 (250 to 461) Ref\n5-17 years 54,310 2,071 (4) 679 (491 to 810) Ref\n≥18 years 279,733 31,167 (11) 756 (61 -189) Ref\n2023 -2024 COVID -19 dose received 7 -59 days earlier\n9 months -4 years 725 18 (2) 32 (20 to 46) 53 (24 to 70)\n5-17 years 951 16 (2) 34 (19 to 47) 64 (41 to 78)\n≥18 years 16,082 1,228 (8) 34 (21 -47) 49 (46 to 52)\n2023 -2024 COVID -19 dose received 60 -299 days earlier\n9 months -4 years 1,345 48 (4) 129 (91 to 178) 23 ( -4 to 43)\n5-17 years 2,510 63 (3) 138 (100 to 185) 34 (14 to 49)\n≥18 years 49,824 4,701 (9) 149 (100 -211) 12 (8 to 15)VE of 2023 –2024 COVID -19 vaccine  doses against emergency \ndepartment/urgent care encounters  — VISION\nSeptember 2023 – August 2024\n-20 0 20 40 60 80 100\nCDC, unpublished data\n* Includes all individuals who did not receive a 2023 -2024 COVID -19 vaccine. For those aged ≥5 years, this includes unvaccinated  persons and persons who were vaccinated with ≥1 original \nmonovalent or bivalent COVID -19 doses. For those aged <5 years, both those in the referent group and those in the vaccinated gro up were required to have completed an initial series. The 2023 -\n2024 dose could have been part of the initial series or in addition to the initial series.\nVaccine effectiveness was calculated by comparing the odds of COVID -19 vaccination in case -patients and control -patients using t he equation: (1 – adjusted odds ratio) x 100%. Odds \nratios were estimated by multivariable logistic regression. The odds ratio was adjusted for age, sex, race and ethnicity, cal end ar day, and geographic region. \n15Age group | COVID -19 vaccination statusTotal\nencountersSARS -CoV -2-\ntest -positive, N (%)Median interval since\nlast dose among\nthose vaccinated,\ndays (IQR) Adjusted vaccine effectiveness % (95% CI)\nNo updated 2024 -2025 COVID -19 vaccine dose*\n9 months -4 years 31,060 809 (3) 392 (282 -662) Ref\n5-17 years 38,870 926 (2) 972 (710 -1,116) Ref\n≥18 years 200,933 12,927 (6) 1,068 (742 -1,224) Ref\n2024 -2025 COVID -19 dose received 7 -179 days earlier\n9 months -4 years 393 2 (1) 64 (30 -98) 79 (17 to 95)\n5-17 years 2,208 22 (1) 81 (44 -122) 57 (33 to 72)\n≥18 years 40,043 1,694 (4) 89 (50 -129) 34 (30 to 37)VE of 2024 -2025 COVID -19 vaccine  doses against emergency \ndepartment/urgent care encounters  — VISION\nSeptember 2024 – May 2025\n-20 0 20 40 60 80 100\nCDC, unpublished data\n* Includes all individuals who did not receive a 2024 -2025 COVID -19 vaccine. For those aged ≥5 years, this includes unvaccinated  persons and persons who were vaccinated with ≥1 original \nmonovalent or bivalent COVID -19 doses. For those aged <5 years, both those in the referent group and those in the vaccinated gro up were required to have completed an initial series. The 2024 -\n2025 dose could have been part of the initial series or in addition to the initial series.\nVaccine effectiveness was calculated by comparing the odds of COVID -19 vaccination in case -patients and control -patients using t he equation: (1 – adjusted odds ratio) x 100%. Odds \nratios were estimated by multivariable logistic regression. The odds ratio was adjusted for age, sex, race and ethnicity, cal end ar day, and geographic region.\nOvercoming COVID -19: Effectiveness* of maternal vaccination† in \nprevention of COVID -19–associated hospitalization  among infants§\nMarch 9, 2022 – May 31, 2023\nSimeone & Zambrano et al., MMWR, 2023: https://www.cdc.gov/mmwr/volumes/72/wr/mm7239a3.htm . \n* VE estimates were based on odds of maternal vaccination during pregnancy in case -patients versus control patients, adjusted fo r U.S. Census Bureau region, admission date (monthly), age (in months), \nsex, and race and ethnicity (non -Hispanic Black or African American, non -Hispanic White, non -Hispanic other, Hispanic or Latino of any race, or unknown). Study site was included as a repeated effect. \nVE was calculated as (1 – adjusted odds ratio) x 100%.\n†Maternal vaccination status was based on the last date of a COVID -19 mRNA vaccine dose: unvaccinated was defined as mothers who  had not received any vaccine dose before or during pregnancy, \nand vaccinated was defined as mothers who received their last dose of a COVID -19 mRNA vaccine between the first day of pregnancy  and 14 days before delivery. Among those vaccinated during \npregnancy, mothers could have received ≥1 dose during pregnancy. Mothers could receive 1 dose of Ad.26.CoV2.S (Janssen [Johns on & Johnson]) vaccine before or during pregnancy and 1 dose of an \nmRNA vaccine during pregnancy. Mothers who received only 1 dose of an mRNA vaccine were considered partially vaccinated and w ere excluded from the analysis. Mothers whose last vaccine dose \noccurred before pregnancy were excluded from the analysis.\n§Infants were excluded from analysis if they were born to mothers who had received their most recent dose before pregnancy, re ceived only 1 dose of an mRNA vaccine, received their most recent \nvaccine dose within 14 days of delivery, received only 1 dose of a viral vector vaccine, or whose vaccination status could no t be verified or whose timing of vaccination was unknown.16Age group of infantNo. vaccinated/Total no. (%)\nInterval between last vaccine dose and infant \nhospitalization, days (IQR)Effectiveness of Maternal Vaccination against Infant Covid -19 \nHospitalization % (95% CI) Case -patients Control patients\n0-5 months 82/377 (22) 94/339 (28) 236 (185 –300) 35 (15 –51)\n0-2 months 43/227 (19) 63/214 (29) 219 (152 –264) 54 (32 –68)\n0 20 40 60 80 100\nVaccine Effectiveness (%)\nEstimates of COVID -19 Vaccine \nEffectiveness in Adults\n17\nAbsolute VE of COVID -19 original  monovalent and bivalent doses received prior to  or during  \npregnancy against COVID -19–associated emergency department/urgent care encounters \namong immuno competent  pregnant women aged 18 -45 years  — VISION\nJune 2022 – August 2023\nVaccine effectiveness was calculated by comparing the odds of COVID -19 vaccination in case -patients and control -patients using t he equation: (1 – adjusted odds ratio) x 100%. Odds ratios were estimated by \nmultivariable logistic regression. The odds ratio was adjusted for a ge, ethnicity, race, underlying medical conditions, gestational age at encounter, site, Medicaid status, day of encounter, site  facility \nurbanicity.\nPregnant women were classified as (1) unvaccinated (no COVID -19 vaccine doses) or (2) vaccinated with the last COVID -19 vaccine dose ≥7 days before the index date (including the original \nmonovalent and/or bivalent vaccines). The index date was defined as (1) the collection date of a respiratory specimen associa ted with the most recent positive or negative SARS -CoV-2 test result \nbefore the ED/UC encounter or (2) the encounter date, if testing occurred only after the encounter. COVID -19 vaccination dates a nd vaccine types were identified by electronic medical records. \nOriginal monovalent COVID -19 vaccines (11 December 2020 –31 August 2022) include Moderna, Pfizer -BioNTech, and Janssen (Johnson &  Johnson), and bivalent COVID -19 vaccines include Moderna \nand Pfizer -BioNTech. Bivalent vaccines (1 September 2022 –10 September 2023) contain components from the SARS -CoV-2 ancestral and  Omicron BA.4/BA.5 strains.\nCiesla et al., OFID 2024, https://academic.oup.com/ofid/article/11/9/ofae481/7743292  18Vaccine Dosage PatternTotal\ntestsSARS -CoV-2-\ntest-positive,\nN (%)Median interval\nsince last dose,\ndays (IQR)Adjusted VE\n(95% CI)\nAbsolute VE\nUnvaccinated (ref) 2991 403 (13) -- Ref\nMost recent monovalent or bivalent dose received:\n≥6 months before pregnancy 3014 365 (12) 483 (393,579) 6 (-11, 21)\n<6 months before pregnancy 1203 143 (12) 267 (204, 325) 28 (11, 42)\nDuring pregnancy 469 35 (7) 91 (45, 158) 52 (29, 67)\n-20 020406080100\nVaccine Effectiveness (%)\nVISION: VE of 2023 -2024  COVID -19 vaccination against COVID -19–associated \nemergency department/urgent care encounters among immuno competent  \nwomen aged 18 -45 years, by pregnancy status  — VISION\nSeptember 2023 – August 2024\nVE=vaccine effectiveness; CLI = COVID -19-like illness\nVaccine eff ectiveness was calculated by comparing the odds of COVID -19 vaccination in case -patients and control -patients using the equation : (1 – adjusted odds ratio) x 100%. Odds \nratios were estimated by multivariable logistic regression. The odds ratio was adju sted for: age, ethnicity, race, underlying medical conditions, gestational age at encounter, site, \nMedicaid status, day of encounter, site facility urbanicity\nCDC unpublished data 19Vaccine Dosage PatternTotal\ntestsSARS -CoV-2-\ntest-positive,\nN (%)Median interval\nsince last dose,\ndays (IQR)Adjusted VE\n(95% CI)\nPregnant at CLI encounter\nNo 2023 -2024 dose (ref) 5058 709 (14) 797 (648, 931) Ref\nMost recent 2023 -2024 dose received 7 -179 days 229 13 (6) 77 (44, 120) 58 (24 -77)\nNot pregnant at CLI encounter\nNo 2023 -2024 dose (ref) 76,636 8,052 (11) 794 (641, 931) Ref\nMost recent 2023 -2024 dose received 7 -179 days 5,079 313 (6) 83 (45, 126) 37 (29 -44)\n-20 020406080100\nVaccine Effectiveness (%)\n20Characteristics of emergency department and urgent care encounters and hospitalizations \namong adults aged ≥18 years with COVID -19-like illness, by COVID -19 case status and CDC \nvaccine effectiveness network — VISION and IVY Networks\nSeptember 2024 –May 2025 \nCharacteristicVaccine effectiveness network and setting, no. (column %)\nVISION\nED/UC encounters,\nall adults aged ≥18 yearsVISION\nhospitalizations,\nall adults aged ≥65 yearsIVY\nhospitalizations,\nall adults aged ≥65 years\nTotalCOVID -19\ncase -\npatientsCOVID -19\ncontrol -\npatients TotalCOVID -19\ncase -\npatientsCOVID -19\ncontrol -\npatients TotalCOVID -19\ncase -\npatientsCOVID -19\ncontrol -\npatients\nTotal 240,976 14,621 226,355 65,751 4,341 61,410 4,392​ 1,190​ 3,202\nMedian age 52 [34, 71] 57 [36, 74] 52 [34, 71] 78 [71, 84] 79 [73, 86] 78 [71, 84] 75 [70, 82]​ 77 [71, 84]​ 75 [69, 81]\nAge group\n18-64 years 158,028 (66) 8,688 (59) 149,340 (66) -- -- -- -- -- --\n≥65 years 82,948 (34) 5,933 (41) 77,015 (34) 65,751 (100) 4,341 (100) 61,410 (100) 4,392 (100) 1,190 (100)​ 3,202 (100)\nImmunocompromised* -- -- -- 15,350 (23)​ 883 (20)​ 14,467 (24)​ 1,137 (26)​ 258 (22)​ 879 (28)\nUpdated from Link -Gelles, et al. MMWR: https://www.cdc.gov/mmwr/volumes/74/wr/mm7406a1.htm\nED/UC = emergency department/urgent care; VISION data go through May 2025; IVY data go through April 2025\n* Immunocompromised status is not evaluated for ED/UC encounters due to a higher likelihood of incomplete discharge diagnosis  codes in this setting.\n21Effectiveness of 2024–2025 COVID -19 vaccination against COVID -19–associated emergency \ndepartment/urgent care  encounters by age group — VISION\nSeptember 2024 – May 2025\nUpdated from: Link -Gelles, et al. MMWR: https://www.cdc.gov/mmwr/volumes/74/wr/mm7406a1.htm . Vaccine effectiveness was calculated by comparing the odds of 2024 –2025 COVID -19 vaccination in case -patients and control -patients using the equation: (1 – adjusted odds \nratio) x 100%. Odds ratios were estimated by multivariable logistic regression. The odds ratio was adjusted for age, sex, rac e and ethnicity, calendar day, and geographic region. The “no 2024 –2025 dose” group included all eligible persons who did not recei ve a 2024 –2025 COVID -19 \nvaccine dose, regardless of number of previous COVID -19 vaccine doses (if any) received.  * Time since vaccination is for most r ecent dose, which could have been an original monovalent, bivalent, 2023 -2024, or 2024 -2025 COVID -19 vaccine.Age group/2024 -2025 COVID -19 vaccination \nstatus/days since doseCOVID -19\ncase -patients\nN (Col %)COVID -19\ncontrol -patients\nN (Col %)Median interval since\nlast dose among\nvaccinated*, days (IQR) Adjusted vaccine effectiveness % (95% CI)\n≥18 years\nNo 2024 -2025 COVID -19 dose  (Ref) 12,927 (88) 188,006 (83) 1,068 (742 -1,224) Ref\nReceived 2024 -2025 COVID -19 dose 7–179 days earlier 1,694 (12) 38,349 (17) 89 (50 -129) 34 (30 -37)\n2024 -2025 COVID -19 dose , 7–59 days earlier 572 (4) 11,763 (5) 34 (21 -47) 36 (30 -42)\n2024 -2025 COVID -19 dose , 60–119 days earlier 695 (5) 14,685 (6) 89 (74 -104) 35 (29 -40)\n2024 -2025 COVID -19 dose , 120 –179 days earlier 427 (3) 11,901 (5) 147 (133 -162) 28 (20 -35)\n18-64 years\nNo 2024 -2025 COVID -19 dose  (Ref) 8,212 (95) 136,067 (91) 1,105 (866 -1,245) Ref\nReceived 2024 -2025 COVID -19 dose 7–179 days earlier 476 (5) 13,273 (9) 86 (48 -127) 32 (25 -38)\n2024 -2025 COVID -19 dose , 7–59 days earlier 156 (2) 4,244 (3) 33 (20 -46) 39 (29 -49)\n2024 -2025 COVID -19 dose , 60–119 days earlier 199 (2) 5,155 (3) 89 (74 -104) 32 (21 -41)\n2024 -2025 COVID -19 dose , 120 –179 days earlier 121 (1) 3,874 (3) 147 (132 -163) 20 (4 -34)\n≥65 years\nNo 2024 -2025 COVID -19 dose  (Ref) 4,715 (79) 51,939 (67) 907 (448 -1,166) Ref\nReceived 2024 -2025 COVID -19 dose 7–179 days earlier 1,218 (21) 25,076 (33) 91 (51 -131) 35 (30 -39)\n2024 -2025 COVID -19 dose , 7–59 days earlier 416 (7) 7,519 (10) 34 (21 -47) 36 (29 -43)\n2024 -2025 COVID -19 dose , 60–119 days earlier 496 (8) 9,530 (12) 90 (75 -105) 36 (29 -42)\n2024 -2025 COVID -19 dose , 120 –179 days earlier 306 (5) 8,027 (10) 147 (133 -162) 30 (21 -39)\n0 20 40 60 80 100\nVaccine effectiveness (%)\n22Effectiveness of 2024–2025 COVID -19 vaccination against COVID -19–associated hospitalization  \namong immunocompetent  adults aged ≥65 years — VISION and IVY Networks\nSeptember 2024 – May 2025\nNetwork/2024 -2025 COVID -19 vaccination status/days \nsince doseCOVID -19 \ncase -\npatients\nN (Col %)COVID -19 \ncontrol -\npatients\nN (Col %)Median interval since\nlast dose among\nvaccinated*, days (IQR) Adjusted vaccine effectiveness % (95% CI)\nVISION\nNo 2024 -2025 COVID -19 dose  (Ref) 2,943 (85) 34,900 (74) 958 (508 -1,187) Ref\nReceived 2024 -2025 COVID -19 dose 7–179 days earlier 515 (15) 12,043 (26) 92 (51 -132) 44 (38 -50)\n2024 -2025 COVID -19 dose , 7–59 days earlier 155 (4) 3,604 (8) 34 (20 -47) 46 (36 -54)\n2024 -2025 COVID -19 dose , 60–119 days earlier 207 (6) 4,509 (10) 90 (75 -104) 50 (42 -57)\n2024 -2025 COVID -19 dose , 120 –179 days earlier 153 (4) 3,930 (8) 147 (133 -162) 32 (19 -43)\nIVY\nNo 2024 -2025 COVID -19 dose  (Ref) 822 (88) 1,824 (79) Not available Ref\nReceived 2024 -2025 COVID -19 dose 7–179 days earlier 110 (12) 499 (21) 92 (55 –130) 46 (32 -58)\n2024 -2025 COVID -19 dose , 7–59 days earlier 43 (5) 124 (5) 32 (20 –46) 42 (16 -60)\n2024 -2025 COVID -19 dose , 60–119 days earlier 37 (4) 205 (9) 89 (73 –103) 53 (32 -68) \n2024 -2025 COVID -19 dose , 120 –179 days earlier 30 (3) 170 (7) 146 (130 –161) 40 (9 -62)\n0 20 40 60 80 100\nVaccine effectiveness (%)Updated from: Link -Gelles, et al. MMWR: https://www.cdc.gov/mmwr/volumes/74/wr/mm7406a1.htm   \nVaccine effectiveness was calculated by comparing the odds of 2024 –2025 COVID -19 vaccination in case -patients and control -patien ts using the equation: (1 – adjusted odds ratio) x 100%. Odds ratios \nwere estimated by multivariable logistic regression. For VISION, the odds ratio was adjusted for age, sex, race and ethnicity , calendar day, and geographic region. For IVY, the odds ratio was adjusted \nfor age, sex, race and ethnicity, geographic region (U.S. Department of Health and Human Services Region) and calendar time ( biweekly intervals). The “no 2024 –2025 dose” group included all eligible \npersons who did not receive a 2024 –2025 COVID -19 vaccine dose, regardless of number of previous COVID -19 vaccine doses. VISION data go through May 2025; IVY data go through April 2025.\n*Time since vaccination is for most recent dose, which could have been an original monovalent, bivalent, 2023 -2024, or 2024 -2025  COVID -19 vaccine.\n23Effectiveness of 2024–2025 COVID -19 vaccination against COVID -19–associated critical illness  \namong immunocompetent  adults aged ≥65 years — VISION and IVY Networks\nSeptember 2024 – May 2025\n2024 -2025 COVID -19 vaccination status/days since \ndoseCOVID -19 \ncase -\npatients\nN (Col %)COVID -19 \ncontrol -\npatients\nN (Col %)Median interval since\nlast dose among\nvaccinated*, days (IQR) Adjusted vaccine effectiveness % (95% CI)\nVISION\nNo 2024 -2025 COVID -19 dose  (Ref) 558 (85) 34,900 (74) 961 (510 -1,189) Ref\nReceived 2024 -2025 COVID -19 dose 7–179 days earlier 97 (15) 12,043 (26) 92 (51 -132) 45 (31 -56)\n2024 -2025 COVID -19 dose , 7–59 days earlier 28 (4) 3,604 (8) 34 (20 -47) 46 (21 -64)\n2024 -2025 COVID -19 dose , 60–119 days earlier 44 (7) 4,509 (10) 90 (75 -104) 45 (25 -60)\n2024 -2025 COVID -19 dose , 120 –179 days earlier 25 (4) 3,930 (8) 147 (133 -162) 43 (13 -62)\nIVY\nAcute respiratory failure\nNo 2024 -2025 COVID -19 dose  (Ref) 158 (88) 1,817 (78) Not available Ref\nReceived 2024 -2025 COVID -19 dose 7–179 days earlier 21 (12) 498 (22) 96 (59 -131) 44 (11 -67)\nICU admission or death\nNo 2024 -2025 COVID -19 dose  (Ref) 141 (91) 1,824 (79) Not available Ref\nReceived 2024 -2025 COVID -19 dose 7–179 days earlier 14 (9) 499 (21) 96 (60 -133) 56 (23 -76)\nInvasive mechanical ventilation or death\nNo 2024 -2025 COVID -19 dose  (Ref) 74 (94) 1,824 (79) Not available Ref\nReceived 2024 -2025 COVID -19 dose 7–179 days earlier 5 (6) 499 (21) 97 (60 -133) 70 (35 -89)\n0 20 40 60 80 100\nVaccine effectiveness (%)\nBased on methods in: Link -Gelles, et al. MMWR: https://www.cdc.gov/mmwr/volumes/74/wr/mm7406a1.htm   \nVaccine effectiveness was calculated by comparing the odds of 2024 –2025 COVID -19 vaccination in case -patients and control -patien ts using the equation: (1 – adjusted odds ratio) x 100%. Odds ratios were estimated by multivariable logistic regression. For VI SION, \nthe odds ratio was adjusted for age, sex, race and ethnicity, calendar day, and geographic region. For IVY, the odds ratio wa s adjusted for age, sex, race and ethnicity, geographic region (U.S. Department of Health and Human Services Region) and calenda r time \n(biweekly intervals). The “no 2024 –2025 dose” group included all eligible persons who did not receive a 2024 –2025 COVID -19 vacci ne dose, regardless of number of previous COVID -19 vaccine doses. VISION data go through May 2025; IVY data go through April 202 5.\nFor VISION, critical illness is defined as admission to the intensive care unit or in -hospital death. For IVY, acute respiratory  failure was defined as new receipt of high -flow nasal canula, noninvasive ventilation, or invasive mechanical ventilation.\n*Time since vaccination is for most recent dose, which could have been an original monovalent, bivalent, 2023 -2024, or 2024 -2025  COVID -19 vaccine.\nICU = intensive care unit\n24Effectiveness of 2024–2025 COVID -19 vaccination against COVID -19–associated hospitalization  \namong immunocompromised  adults aged ≥65 years — VISION and IVY Networks\nSeptember 2024 – May 2025\nNetwork/2024 -2025 COVID -19 vaccination status/days \nsince doseCOVID -19 \ncase -\npatients\nN (Col %)COVID -19 \ncontrol -\npatients\nN (Col %)Median interval since\nlast dose among\nvaccinated*, days (IQR) Adjusted vaccine effectiveness % (95% CI)\nVISION\nNo 2024 -2025 COVID -19 dose  (Ref) 719 (81) 10,035 (69) 882 (451 -1,166) Ref\nReceived 2024 -2025 COVID -19 dose 7–179 days earlier 164 (19) 4,432 (31) 93 (53 -133) 38 (25 -48)\n2024 -2025 COVID -19 dose , 7–59 days earlier 62 (7) 1,247 (9) 35 (20 -47) 25 (2 -43)\n2024 -2025 COVID -19 dose , 60–119 days earlier 61 (7) 1,689 (12) 89 (75 -104) 47 (30 -60)\n2024 -2025 COVID -19 dose , 120 –179 days earlier 41 (5) 1,496 (10) 147 (133 -163) 39 (14 -57)\nIVY\nNo 2024 -2025 COVID -19 dose  (Ref) 214 (83) 670 (76) Not available Ref\nReceived 2024 -2025 COVID -19 dose 7–179 days earlier 44 (17) 209 (24) 82 (48 -133) 36 (6 -57) \n0 20 40 60 80 100\nVaccine effectiveness (%)\nUpdated from: Link -Gelles, et al. MMWR: https://www.cdc.gov/mmwr/volumes/74/wr/mm7406a1.htm  \nVaccine effectiveness was calculated by comparing the odds of 2024 –2025 COVID -19 vaccination in case -patients and control -patien ts using the equation: (1 – adjusted odds ratio) x 100%. Odds \nratios were estimated by multivariable logistic regression. For VISION, the odds ratio was adjusted for age, sex, race and et hnicity, calendar day, and geographic region. For IVY, the odds ratio was \nadjusted for age, sex, race and ethnicity, geographic region (U.S. Department of Health and Human Services Region) and calend ar time (biweekly intervals). The “no 2024 –2025 dose” group included \nall eligible persons who did not receive a 2024 –2025 COVID -19 vaccine dose, regardless of number of previous COVID -19 vaccine do ses (if any) received. VISION data go through May 2025; IVY data \ngo through April 2025.\n* Time since vaccination is for most recent dose, which could have been an original monovalent, bivalent, 2023 -2024, or 2024 -2025 COVID -19 vaccine.\n25IVY: Effectiveness of 2024–2025 COVID -19 vaccine against hospitalization \namong adults aged ≥18 years by SARS -CoV-2 lineage using viral whole -\ngenome sequencing\n•Population\n•Cases:  COVID -like illness (CLI) and test positive for SARS -CoV-2*;restricted to patients with sequence -\nconfirmed†KP.3.1.1 lineage (Nextstrain  clade 24E)  or XEC lineage (Nextstrain  clade 24F)\n•Controls: CLI and test negative forSARS -CoV-2, influenza viruses, and RSV (≥60 years) byRT-PCR\n•Analytic Period: September 1, 2024 –April 27, 2025\n•VE§ against hospitalization was calculated separately using case -patients with sequence -confirmed SARS -\nCoV-2 KP .3.1.1 and XEC lineage infections\n* Case patients who were co -infected with influenza viruses or RSV were excluded.\n† Identification of a SARS -CoV-2 lineage through viral whole -genome sequencing was successful for 49% of case -patients during the  analysis period.\n§ Vaccine effectiveness was calculated by comparing the odds of 2024 –2025 COVID -19 vaccination in case -patients and control -patien ts using the equation: (1 – adjusted odds ratio) x 100%. \nOdds ratios were estimated by multivariable logistic regression.  The odds ratio was adjusted for age, sex, race and ethnicity, geographic region (U.S. Department of Health and Human Services \nRegion) and calendar time (biweekly intervals).\nLineage and 2024 -2025 COVID -19 \nvaccination statusCOVID -19 case -patients COVID -19 control -patients\nVaccine Effectiveness§% (95% CI)  N (Col %)Median interval\nsince last dose \namong \nvaccinated,\ndays (IQR) N (Col %)Median interval \nsince last dose \namong \nvaccinated,\ndays (IQR)\nKP.3.1.1\nNo 2024 -2025 COVID -19 dose (Ref) 309 (91) Not available  5,202 (84) Not available  Ref\nReceived 2024 -2025 COVID -19 dose 7–179 days earlier 29 (9) 56 (33 –75) 1,027 (16) 94 (57 –133) 45 (19 –64)\nXEC\nNo 2024 -2025 COVID -19 dose (Ref) 173 (84) Not available  5,202 (84) Not available  Ref\nReceived 2024 -2025 COVID -19 dose 7–179 days earlier 32 (16) 87 (52 –112) 1,027 (16) 94 (57 –133) 34 (2 –57)\n* These results include both immunocompetent and immunocompromised persons.\n† KP.3.1.1 lineage was defined by Nextstrain  clade 24E and XEC lineage was defined by Nextstrain  clade 24F.\n§ Vaccine effectiveness was calculated by comparing the odds of 2024 –2025 COVID -19 vaccination in case -patients and control -patien ts using the equation: (1 – adjusted odds ratio) x 100%. Odds ratios were \nestimated by multivariable logistic regression.  The odds ratio was adjusted for age, sex, race and ethnicity, geographic region (U.S. Department of Health and Human Services Re gion) and calendar time \n(biweekly intervals).-20 0 20 40 60 80 100\nVaccine  Effectiveness (%)IVY: Effectiveness of 2024–2025 COVID -19 vaccine against hospitalization \namong adults aged ≥18 years* by SARS -CoV-2 lineage †\nSeptember 1, 2024 – April 27, 2025\n27•For the respective year, compared to no in -season dose, COVID -19 vaccination provided additional protection \nagainst:\n-COVID -19-associated emergency department and urgent care* visits among children ; protection was generally similar across age \ngroups.\n-COVID -19-associated emergency department and urgent care visits among adults .\n-COVID -19-associated hospitalizations among adults aged ≥65 years with and without immunocompromising conditions .\n-COVID -19-associated critical illness among adults aged ≥65 years ; protection appeared to be higher and more durable against critical \nillness compared to less severe outcomes.\n•VE should be interpreted as the added benefit of 2023 –2024 or 2024 –2025 COVID -19 vaccination in a population \nwith high levels of infection -induced immunity, vaccine -induced immunity, or both.    \n-Prior SARS -CoV-2 infection contributes protection against future disease, though protection wanes over time. \n-An increase in SARS -CoV-2 circulation in the United States during late summer 2024, just before the 2024 –2025 COVID -19 vaccines \nwere approved and authorized, may have resulted in higher population -level immunity against JN.1 -lineage strains, which could ha ve \nresulted in lower measured VE than in a population with less recent infection.Conclusions: effectiveness of COVID -19 vaccines\n* Due to lower baseline rates of severe disease and lower COVID -19 vaccine coverage, VE against hospitalization and critical ill ness in children could not be estimated.\n28Data and analysis were provided by CDC and the \nfollowing CDC -funded network partners:\nVISION Collaborators\nIVY Collaborators\nOvercoming Collaborators\nBack -up\n30Context for interpreting COVID -19 VE across age groups: high infection -\ninduced seroprevalence in children and adults\n* Data on persons aged 0 -17 years from nationwide commercial laboratory testing of residual serum specimens from ~27,000 childre n and adolescents originally submitted for routine screening or clinical management, \nhttps://covid.cdc.gov/covid -data -tracker/#pediatric -seroprevalence\n** Data on persons aged ≥16 years from a longitudinal, national cohort of ~35,000 blood donors, https://covid.cdc.gov/covid -data -tracker/#nationwide -blood -donor -seroprevalence -2022 89%\n92%\n87%\n76%16-29 years\n30-49 years\n50-64 years\n≥65 years\n0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%\nPercent with infection -induced immunityPercent of persons with infection -induced immunity, based on anti -nucleocapsid results from blood donors,\nadolescents and adults , October – December 2023**\nVE findings should be interpreted as the added benefit provided by COVID -19 vaccination in a \npopulation with a high prevalence infection -induced immunity.91%\n93%0-11 years\n12-17 yearsPercent of persons with infection -induced immunity, based on anti -nucleocapsid results from residual specimens from commercial l aboratories,\nchildren and adolescents , November – December 2022*Age at blood draw\n31Age group/2023 -2024 COVID -19 vaccination \nstatus/days since doseTotal\nencountersSARS -CoV -2-\ntest -positive,\nN (%)Median interval since\nlast dose among\nvaccinated, days (IQR) Adjusted VE (95% CI)\n≥18 years\nNo 2023 -2024 COVID -19 dose (ref) 279,733 31,167 (11) 756 (543 -920) ref\n2023 -2024 COVID -19 dose , 7-299 days earlier 65,906 5,929 (9) 117 (61 -189) 24 (21 to 26)\n2023 -2024 COVID -19 dose , 7-59 days earlier 16,082 1,228 (8) 34 (21 -47) 49 (45 to 52)\n2023 -2024 COVID -19 dose , 60-119 days earlier 17,653 1,521 (9) 88 (73 -103) 26 (22 to 30)\n2023 -2024 COVID -19 dose , 120 -179 days earlier 13,815 875 (6) 147 (133 -163) 18 (12 to 24)\n2023 -2024 COVID -19 dose , 180-299 days earlier 18,356 2,305 (13) 231 (204 -261) -7 (-13 to -2)\n18-64 years\nNo 2023 -2024 COVID -19 dose (ref) 200,443 21,053 (10) 789 (624 -934) ref\n2023 -2024 COVID -19 dose , 7-299 days earlier 23,655 1,893 (8) 116 (59 -187) 22 (18 to 26)\n2023 -2024 COVID -19 dose , 7-59 days earlier 5,952 360 (6) 34 (20 -47) 55 (49 to 59)\n2023 -2024 COVID -19 dose , 60-119 days earlier 6,285 436 (7) 88 (74 -104) 29 (22 to 36)\n2023 -2024 COVID -19 dose , 120 -179 days earlier 4,971 256 (5) 147 (133 -163) 22 (11 to 31)\n2023 -2024 COVID -19 dose , 180-299 days earlier 6,447 841 (13) 230 (203 -260) -24 ( -34 to -14)\n≥65 years\nNo 2023 -2024 COVID -19 dose (ref) 79,290 10,114 (13) 669 (436 -868) ref\n2023 -2024 COVID -19 dose , 7-299 days earlier 42,251 4,036 (10) 117 (62 -190) 25 (22 to 28)\n2023 -2024 COVID -19 dose , 7-59 days earlier 10,130 868 (9) 34 (21 -47) 46 (41 to 50)\n2023 -2024 COVID -19 dose , 60-119 days earlier 11,368 1,085 (10) 88 (73 -103) 25 (20 to 30)\n2023 -2024 COVID -19 dose , 120 -179 days earlier 8,844 619 (7) 148 (133 -163) 19 (11 to 26)\n2023 -2024 COVID -19 dose , 180-299 days earlier 11,909 1,464 (12) 232 (204 -262) 2 (-5 to 8)VISION: VE of 2023 -2024 COVID -19 vaccine against COVID -19-associated emergency \ndepartment/urgent care encounters among immunocompetent adults aged ≥18 years, by age group\nSeptember 2023 – August 2024\nLink-Gelles et al. in press, JAMA Network Open. VE was calculated as (1 − odds ratio) x 100%, estimated using a test -negative case -control design, with the odds ratio adjusted for age, sex, race and ethnicity, \ngeographic region, and calendar time. A VE estimate less than zero is possible due to the waning protection from COVID -19 vaccin es coupled with the existing infection -induced immunity in unvaccinated \nparticipants. As protection from vaccination wanes, and unvaccinated people accumulate protection from repeated infections, t his may yield negative VE. -40 -20 0 20 40 60 80 100\n32VISION: VE of 2023 -2024 COVID -19 vaccine against COVID -19-associated \nhospitalization among immunocompetent adults aged ≥18 years, by age group\nSeptember 2023 – August 2024\nAge group/2023 -2024 COVID -19 vaccination \nstatus/days since doseTotal\nencountersSARS -CoV -2-\ntest -positive,\nN (%)Median interval since\nlast dose among\nvaccinated, days (IQR) Adjusted VE (95% CI)\n≥18 years\nNo 2023 -2024 COVID -19 dose (ref) 87,718 8,480 (10) 733 (507 -918) ref\n2023 -2024 COVID -19 dose , 7-299 days earlier 24,213 1,900 (8) 123 (63 -193) 29 (25 to 33)\n2023 -2024 COVID -19 dose , 7-59 days earlier 5,618 417 (7) 34 (21 -47) 51 (46 to 56)\n2023 -2024 COVID -19 dose , 60-119 days earlier 6,231 486 (8) 88 (74 -104) 36 (30 to 42)\n2023 -2024 COVID -19 dose , 120 -179 days earlier 5,275 306 (6) 149 (134 -164) 22 (12 to 31)\n2023 -2024 COVID -19 dose , 180-299 days earlier 7,089 691 (10) 230 (203 -260) -4 (-14 to 5)\n18-64 years\nNo 2023 -2024 COVID -19 dose (ref) 35,303 2,229 (6) 788 (606 -940) ref\n2023 -2024 COVID -19 dose , 7-299 days earlier 4,249 234 (6) 120 (62 -188) 15 (2 to 27)\n2023 -2024 COVID -19 dose , 7-59 days earlier 1,005 60 (6) 33 (21 -46) 31 (10 to 47)\n2023 -2024 COVID -19 dose , 60-119 days earlier 1,113 52 (5) 89 (75 -104) 33 (11 to 50)\n2023 -2024 COVID -19 dose , 120 -179 days earlier 936 33 (4) 148 (135 -164) 21 ( -12 to 45)\n2023 -2024 COVID -19 dose , 180-299 days earlier 1,195 89 (7) 229 (201 -259) -31 ( -66 to -4)\n≥65 years\nNo 2023 -2024 COVID -19 dose (ref) 52,415 6,251 (12) 698 (467 -899) ref\n2023 -2024 COVID -19 dose , 7-299 days earlier 19,964 1,666 (8) 123 (63 -194) 31 (27 to 35)\n2023 -2024 COVID -19 dose , 7-59 days earlier 4,613 357 (8) 34 (21 -47) 54 (49 to 59)\n2023 -2024 COVID -19 dose , 60-119 days earlier 5,118 434 (8) 88 (73 -104) 36 (29 to 42)\n2023 -2024 COVID -19 dose , 120 -179 days earlier 4,339 273 (6) 149 (134 -164) 21 (10 to 31)\n2023 -2024 COVID -19 dose , 180-299 days earlier 5,894 602 (10) 230 (204 -261) 0 (-10 to 10)\n-80 -60 -40 -20 020 40 60 80 100Link-Gelles et al. in press, JAMA Network Open. VE was calculated as (1 − odds ratio) x 100%, estimated using a test -negative case -control design, with the odds ratio adjusted for age, sex, race and ethnicity, \ngeographic region, and calendar time. A VE estimate less than zero is possible due to the waning protection from COVID -19 vaccin es coupled with the existing infection -induced immunity in unvaccinated \nparticipants. As protection from vaccination wanes, and unvaccinated people accumulate protection from repeated infections, t his may yield negative VE. \nIVY: Number of COVID -19 case -patients by hospital admission week and SARS -\nCoV-2 lineage\nSeptember 1, 2024 –April 27, 2025 \nDates are for the start of the admission week. \n\n34*Data sources included Medicare Enrollment Database (EDB) and Common Medicare Environment (CME), Common Working File (CWF) an d Shared System Data (SSD) Medicare Parts A/B claims data, Minimum Data Set (MDS), and CDC/ATSDR \nSocial Vulnerability Index (SVI)\n**Hazard ratios adjusted for age group, sex, race, long/short nursing home stay status, social vulnerability index, state, ru ral/urban classification, number of underlying medical conditions, 2022 -2023 influenza vaccination status, and bivalent\nCOVID -19 vaccination status.Medicare data\n• Design: Retrospective cohort\n• Data source:  Medicare fee -for-service claims data*\n• Population:  Persons aged ≥65, recent nursing home \nstay \n• Censoring events: ​\n– COVID -19-associated thromboembolic event​ (TE)\n– Death​\n– Disenrollment in Medicare Parts A/B​\n– Enrollment in Medicare Part C​\n– Admission to hospice facility​\n– Dialysis encounter\n– Receipt of a 2023 -2024 COVID -19 vaccine dose <60 days from \nbivalent COVID -19 vaccine dose\n– Receipt of a second 2023 -2024 COVID -19 vaccine dose <120 days \nfrom first 2023 -2024 COVID -19 vaccine dose\n– Receipt of a third 2023 -2024 COVID -19 vaccine dose\n– End of study period\n• VE = (1 - adjusted hazard ratio**) x 100%\nwhere adjusted hazard ratio = 𝑟𝑎𝑡𝑒  𝑜𝑓 𝐶𝑂𝑉𝐼𝐷 −19−𝑎𝑠𝑠𝑜𝑐𝑖𝑎𝑡𝑒𝑑  𝑇𝐸𝑣𝑎𝑐𝑐𝑖𝑛𝑎𝑡𝑒𝑑\n𝑟𝑎𝑡𝑒  𝑜𝑓 𝐶𝑂𝑉𝐼𝐷 −19−𝑎𝑠𝑠𝑜𝑐𝑖𝑎𝑡𝑒𝑑  𝑇𝐸𝑢𝑛𝑣𝑎𝑐𝑐𝑖𝑛𝑎𝑡𝑒𝑑\nCOVID -19 TEOther Censoring Event\nUnvaccinated person -time\nVaccinated person -time\nStart Follow -up End Study Period\n35Age group/2023 -2024 COVID -19 vaccination \nstatus/days since doseNumber of \nBeneficiariesNumber of \nOutcomesMedian Follow -up Time \nContributed to Category \n(Days) Adjusted VE (95% CI)\n≥65+ years\nNo 2023 -2024 COVID -19 dose (ref) 516,176 4,335 142 Ref\n2023 -2024 COVID -19 dose , ≥ 7 days earlier 209,228 726 161 31% (25%, 36%)\n2023 -2024 COVID -19 dose , 7-59 days earlier 26,646 198 53 50% (42%, 56%)\n2023 -2024 COVID -19 dose , 60-119 days earlier 37,426 238 60 29% (20%, 38%)\n2023 -2024 COVID -19 dose , 120 -179 days earlier 23,558 138 60 15% (0%, 28%)\n2023 -2024 COVID -19 dose , ≥ 180  days earlier 121,598 152 65 0% ( -17%, 14%)\n65-74 years\nNo 2023 -2024 COVID -19 dose (ref) 116,278 1,025 176 Ref\n2023 -2024 COVID -19 dose , ≥ 7 days earlier 40,719 132 178 29% (16%, 39%)\n2023 -2024 COVID -19 dose , 7-59 days earlier 5,029 34 53 47% (36%, 57%)\n2023 -2024 COVID -19 dose , 60-119 days earlier 6,646 55 60 26% (11%, 39%)\n2023 -2024 COVID -19 dose , 120 -179 days earlier 4,984 22 60 12% ( -9%, 29%)\n2023 -2024 COVID -19 dose , ≥ 180  days earlier 24,060 21 64 -5% ( -29%, 15%)\n≥75+ years\nNo 2023 -2024 COVID -19 dose (ref) 399,898 3,310 135 Ref\n2023 -2024 COVID -19 dose , ≥ 7 days earlier 168,509 594 157 31% (25%, 37%)\n2023 -2024 COVID -19 dose , 7-59 days earlier 21,617 164 53 50% (42%, 57%)\n2023 -2024 COVID -19 dose , 60-119 days earlier 30,780 183 60 30% (20%, 39%)\n2023 -2024 COVID -19 dose , 120 -179 days earlier 18,574 116 60 16% (1%, 29%)\n2023 -2024 COVID -19 dose , ≥ 180  days earlier 97,538 131 65 1% ( -17%, 16%)VE of 2023 -2024 COVID -19 vaccine against COVID -19 related thromboembolic events among immunocompetent  \nMedicare fee -for-service beneficiaries residing in a nursing home, by age group and time since vaccination\nSeptember 2023 – July 2024\n-40 -20 0 20 40 60 80 100\nCDC, unpublished data\nModels are adjusted for age group, sex, race, long/short NH stay status, social vulnerability index (SVI), state, rural/urban classification, number of UMC categories, 2022 -2023 influenza vaccination status, and bivalent COVID -19 vaccination \nstatus.  \nInfection -induced SARS -CoV-2 seroprevalence among U.S. \nchildren — September 2021 – December 2022\n36\nInfection -induced (nucleocapsid \nantibody) seroprevalence\nMonth and Year\nShaded ranges depict 95% confidence intervals for the estimated seroprevalence shown by the dark line in the corresponding co lor. \nSource: https://covid.cdc.gov/covid -data -tracker/#pediatric -seroprevalence   \nAccessed: March 20, 20256-11 months\nPopulation SARS -CoV -2 spike antibody over time by the cumulative \nnumber of combined infections and vaccinations - U.S. blood donors ages \n≥16 years, September 2021 -December 2023\nSolid lines represent mean anti -spike IgG levels; dotted lines represent model based 25th-75th% percentiles\nHigher number of cumulative SARS -CoV-2 infections and COVID -19 vaccinations leads to higher antibody \nlevels, but with smaller incremental increases in antibodies with each exposure\nSpike IgG BAU/mL\nSource: https://covid.cdc.gov/covid -data -tracker/#nationwide -blood -donor -seroprevalence -2022 , CDC unpublished data 9\n381. Yousaf AR, Mak J, Gwynn L, et al. COVID -19 Vaccination and Odds of Post –COVID -19 Condition Symptoms in Children Aged 5 to 17 Years. JAMA Netw Open. 2025;8(2):e2459672.\n2. Mak J, Khan S, Britton A et al. Association of Messenger RNA Coronavirus Disease 2019 (COVID -19) Vaccination and Reductions i n Post COVID Conditions Following Severe Acute Respiratory Syndrome \nCoronavirus 2 Infection in a US Prospective Cohort of Essential Workers, The Journal of Infectious Diseases, Volume 231, Issu e 3, 15 March 2025, Pages 665 –676COVID -19 mRNA vaccination associated with reduced occurrence \nof Long COVID following COVID -19: June 2021 -September 2022\nAmong children aged 5 – 17 years:\nCompletion of the primary vaccine \nseries prior to infection associated \nwith reduced likelihood of Long \nCOVID symptoms1\n•57% for 1 or more symptoms\n•73% for 2 or more symptoms\n•72% for respiratory symptomsAmong adults: \n3 doses of original monovalent vaccine \nprior to infection associated with \nreduced likelihood of Long COVID \nsymptoms2\n•63% for gastrointestinal symptoms\n•44% for neurological symptoms \n•52% for other non -specific \nsymptoms \n•Data that explicitly quantifies vaccine effectiveness against transmission is ideal, \nbut it is often not feasible. \n•Other data can help us understand the impact of COVID -19 vaccination on \ntransmission, vaccine effectiveness against infection and infectiousness\n-COVID -19 vaccines provide moderate protection against infection in older children and adults.1,2,3 \n-COVID -19 vaccines may provide less protection against infection in young, infection -naïve \nchildren.4\n-COVID -19 vaccines moderately reduce infectiousness in individuals after they are infected with \nSARS -CoV-2 (see next slides).5\n•Preventing infections further reduces transmission by stopping future transmission \nchains. COVID -19 vaccine impact on transmission\n1 Feldstein L, et al. Effectiveness of mRNA COVID -19 Vaccines and Hybrid Immunity in Preventing SARS -CoV-2 Infection and Symptomatic COVID -19 Among Ad ults in the United States. \nhttps://academic.oup.com/jid/article/231/4/e743/7945315  \n2 Feldstein L , et al. Effectiveness of Bivalent mRNA COVID -19 Vaccines in Preventing SARS -CoV-2 Infection in Children and Adolescents Aged 5 to 17 Yea rs. https://jamanetwork.com/journals/jama/fullarticle/2814536  \n3 Kirwan PD, et al. Protection of vaccine boosters and prior infection against mild/asymptomatic and moderate COVID -19 infection in the UK SIREN hea lthcare worker cohort: October 2023 to March 2024. \nhttps://www.sciencedirect.com/science/article/pii/S0163445324002275?via%3Dihub  \n4 Feldstein L , et al. Protection From COVID -19 Vaccination and Prior SARS -CoV-2 Infection Among Children Aged 6 Months –4 Years, United States, Septemb er 2022 –April 2023 \nhttps://academic.oup.com/jpids/article/14/1/piae121/7917119  \n5 CDC. Respiratory Illness: Gauge of Household Transmission (RIGHT) Study​, unpublished with manuscript in progress.\n40COVID -19 Vaccine Effectiveness against SARS -CoV-2 (SCV2) Infectiousness\nRespiratory  Illness: Gauge of Household Transmission (RIGHT) Study\nProspective household transmission study of SARS -CoV-2, January 2024 –January 2025\nPreliminary analysis (unpublished, manuscript in progress) from RIGHT Study shared by research teams at CDC, Vanderbilt Unive rsity Medical Center, University of Washington, and Columbia \nUniversity Irvin Medical Center.\nIndividuals with SARS -CoV-2 infection who had received a COVID -19 \nvaccination within prior 6 months had lower risk of transmitting to other \nhousehold contacts. Vaccine effectiveness at reducing transmission to \nothers was 45%.\nPreliminary analysis (unpublished, manuscript is progress) from RIGHT Study Jan 2024 -Jan 2025 shared by research teams at CDC, V anderbilt University Medical Center, University of Washington, and \nColumbia University Irvin Medical Center. *Adjusted for age of contact, COVID -19 vaccination status of contact, age of primary case, enrollment state, number of people in  the \nhome, enrollment timing, and clustering by household\n† Vaccine effectiveness against infectionAdjusted* Risk of SARS -CoV-2 Infection in Household Contact by Primary Case Vaccination Status\n†", "summary": "Updates to COVID -19 Vaccine Effectiveness COVID -19 Session Coronavirus and Other Respiratory Viruses Division June 25, 2025National Center for Immunization and Respiratory Diseases   2•Vaccine effectiveness methods & context •Estimates of COVID -19 Vaccine Effectiveness in Children •Estimates of COVID -19 Vaccine Effectiveness in Adults •ConclusionsAgenda –COVID -19 vaccine effectiveness (VE) Methods & Context 3 4 Case ControlPerson with acute respiratory illness SARS -CoV-2 test COVID -19 …", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-25-26-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-06-25-26/03-MacNeil-COVID-508.pdf", "doc_date": "2025-06-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 41}
{"title": "04 Meyer COVID 508", "content": "Update on CDC’s COVID-19 Vaccine Safety Monitoring \nSarah Meyer, MD MPH \nDirector, CDC’s Immunization Safety Office \nJune 25, 2025 \n1 \n \n          \n   \n         \n   \n       \n            \n   \n        Key Points \n• CDC and interagency partners launched an extensive vaccine safety monitoring \nprogram for COVID-19 vaccines \n• Many potential safety outcomes were rigorously assessed through complementary passive and active systems \n• Myocarditis is causally associated with mRNA COVID-19 vaccines \n-Adverse events common to all vaccines were also observed (e.g., local and \nsystemic reactions, allergic reactions) \n• CDC continues to monitor the safety of COVID-19 vaccines \n2 \n   \n  \n \n \nInteragency collaboration to \nmonitor post-licensure safety \nCDC \nmonitoring \nstarts \n3 \n       \n   \n \n       \n        CDC’s Immunization Safety Office Monitors Vaccine Safety \nThrough Strong, Complementary Systems \nVAERS VSD CISA Project V-safe \n1990 1990 2001 2020 \nSystems work together to rapidly detect and assess potential \nsafety concerns to help inform public health actions \n4 \n     \n    \n       \n     \n      \n      \n            \n \n        \n          \nVAERS \nVaccine Adverse Event Reporting System (VAERS) \nThe Nation’s Early Warning System for Vaccine Safety \n• Co-managed by CDC and FDA \n• Nationwide spontaneous reporting system that can rapidly \ndetect safety signals, including rare events \n• Mandated reporting by healthcare providers and \nmanufacturers, and encouraged from anyone (e.g., patients) \n• A report to VAERS does not mean that a vaccine caused an adverse event \n• Used for signal detection and hypothesis generation, not \ntypically for assessing causality \n5 \n      \n   \n       \n  \n        \n   \n     \n       \n      Vaccine Safety Datalink (VSD) \nCollaborative Model for High-Quality Vaccine Safety Data \nVSD • 13 integrated healthcare organizations, covering >15.5 \nmillion people per year \n• Acti\nve monitoring using electronic medical records (EMR) \nand chart reviews \n• Rapid monitoring for pre-specified events as well as \nmonitoring for unexpected events \n• Can detect and assess safety signals \n• Develops innovative methods for monitoring safety \n6 \n       \n     \n \n    \n        \n       \n          Clinical Immunization Safety Assessment (CISA) Project \nNetwork to Guide Vaccine Safety from the Individual to Population Level \nCISA Project • 8 medical research centers with vaccine safety experts \n• Pro\nvides expert clinical consultation on complex \nimmunization issues \n• Conducts clinical research on vaccine safety \n• Helps to inform CDC public health guidance on clinical \nimmunization safety issues \n7 \n     \n   \n         \n       \n        \n     \n        \n     \n      \nV-safe: After-Vaccination Health Checker \nCDC’s Tool for Direct-to-Consumer Vaccine Safety Monitoring \nV-safe • Web-based, self-reported active monitoring system \nestablished during COVID-19 pandemic \n• Can ser\nve as earliest source of information for new \nvaccines and in populations excluded from clinical trials \n-Used to recruit women for COVID-19 Vaccine Pregnancy \nRegistry \n• Important tool for emergency preparedness and response \n• Integrated with VAERS to help streamline reporting of \nser\nious adverse events \n8 \n \n  \n  \n   \n   \n   \n   \n   \n   \n   \n  \n    \n        \n  \n   \n   CDC’s Comprehensive Approach to Studying COVID-19 Vaccine Safety \nSurveillance Epidemiologic studies Clinical Research Pregnancy Registry \nAna\nlyze spontaneously Assess specific safety Safety studies to guide Longitudinal assessment of \nreported events questions clinical practice maternal and infant outcomes \nRapid cycle analyses Dat a mining Pati ent surveys \nQui\nckly detect potential Ass\ness >60,000 outcomes Ass\ness symptoms and \ncon\ncerns for investigation for \nunexpected events hea\nlth impacts \n9 \n         \n    \n  \n \n \n   \n   \n  \n   \n    \n  \n                   CDC Summary of COVID-19 Vaccine Safety Data Based on \nComprehensive Body of Evidence Collected \nDecember 2020 – June 2025 \n17 28 29 114 ~9.6M \nVaST work \ngroup reports Advisory \nmeeting \npresentations \n(ACIP, VRBPAC) Morbidity and \nMortality Weekly \nReport (MMWR) \npublications Published \nmanuscripts Participants \nenrolled in V-safe \nVaccine doses distributed in U.S. ~1B\nACIP: Advisory Committee on Immunization Practices; VRBPAC: Vaccines and Related Biological Products Advisory Committee; VaST: Vaccine Safety Technical Work Group 10 \n       \n      \n \n mRNA \nPfizer-BioNTech \nModerna Three Types of COVID-19 Vaccine Received FDA \nAuthorization or Approval in the United States \nProtein-based \nNovavax \nViral Vector \nJanssen \n11 \n   \n                      \n           \n        \n   \n      \n     \n    \n  \n     -Janssen Use Limited After Detection of Safety Concerns in \nApril 2021, and No Longer Authorized in U.S. as of June 2023 \nProtein-based \nNovavax \nmRNA \nPfizer-BioNTech \nModerna \nEUA: Emergency Use Authorization \nOliver S, et al. Development of COVID-19 vaccine policy — United States, 2020–2023 - ScienceDirect \nViral Vector \nJanssen \n• By April 2021, VAERS detects 6 reports of \nthrombosis w/ thrombocytopenia \nsyndrome (TTS); FDA and CDC issue a 10 \nday pause in use before resuming \n• In December 2021, ACIP issues preferential \nrecommendation for mRNA vaccines \n• In June 2023, FDA revokes EUA \n12 \n          \n           \n    \n   \n   \n    \n  \n   \n            Janssen Use Limited After Detection of Safety Concerns in \nApril 2021, and No Longer Authorized in U.S. as of June 2023 \nProtein-based \nNovavax \nmRNA \nPfizer-BioNTech \nModerna \nEUA: Emergency Use Authorization \nOliver S, et al. Dev\nelopment of COVID-19 vaccine policy — United States, 2020–2023 - ScienceDirect \nViral Vector \nJanssen \nHighlights an example of \nfederal safety systems \nworking to rapidly \nidentify and mitigate a \nvaccine safety issue \n13 \n      \n \n    \n    \n \n    mRNA\nPfizer-BioNTech\nModerna -Limited Post-Authorization Safety Data Available for Novavax \nProtein-based \nNovavax \nLimited post authorization safety data \navailable: \n• Authorized later than other products (July 2022) \n• Limited uptake in the U.S. \nmRNA \nPfizer-BioNTech \nModerna \nViral Vector \nJanssen \n14 \n       \n \n mRNA \nPfizer-BioNTech \nModerna Focus on mRNA COVID-19 Vaccines For This Presentation \nProtein-based \nNovavax \nViral Vector \nJanssen \n15 \n    \n   Monitoring Safety of COVID-19 Vaccines \nWhat we have learned \n16 \n16 \n           \n         CDC Has Evaluated At Least 65 Specific Outcomes to Assess COVID-19 \nVaccine Safety Using a Variety of Systems and Epidemiologic Methods \nAcute myocardial infarction • ICU admission • Acute disseminated encephalomyelitis • Thrombotic \nthrombocytopenic Purpura • Encephalopathy • Gestational diabetes • Trigeminal neuralgia and \nrelated disorders • Meningitis • Deep vein thrombosis • Anaphylaxis • Thrombocytopenia • \nPostmenopausal bleeding • Myocarditis • Cataplexy • Myelitis • Chronic inflammatory demyelinating \npolyneuropathy • Non-COVID mortality • Pulmonary embolism • Stillbirth • Major birth defects • \nEncephalitis •Local reactions •Vaccine-Associated Enhanced Disease after COVID-19 Vaccines \n• Hemorrhagic stroke • Administration errors • Acute respiratory distress syndrome • Narcolepsy • \nPerinatal death •Bell's Palsy •Thrombosis with thrombocytopenia syndrome •Multiple sclerosis \n• Systemic reaction\ns • Spontaneous abortion • Ataxia • Hospitalization • Acute disseminated \nencephalomyelitis • Menstrual irregularities • Immune thrombocytopenic purpura • All-cause \nmortality • Pericarditis •Early childhood infections in infants of vaccinated mothers •Ischemic stroke \n• Shoulder injuries • Multisystem Inflammatory Syndrome in Children • Multisystem Inflammatory \nSyndrome in Adults • Tinnitus • Disseminated intravascular coagulation • Acute respiratory distress \nsyndrome • Venous thromboembolism • Arthritis • Seizure • Kawasaki Disease • Arthralgia • \nMenstrual irregularities •NICU admission •Chronic inflammatory demyelinating polyneuropathy \n•Small-for-gestational age •Post-COVID conditions •Trigeminal neuralgia and related disorders \n17 \n    \n    \n         \n          \n         \n      \n      \n       \n        \n        \n  \n         \n    \nWeekly, Sequential Monitoring of \nPre-Specified Outcomes in the VSD \n• Rapid cycle analyses (RCAs) conducted weekly since December 2020 \nof up to 23 pre-specified outcomes among over 12 million people \n-Outcomes selected based on clinical trial data, known safety \nfindings with other vaccines, or biological plausibility \n• Seq\nuential statistical testing using automated ICD-10-CM codes \n-Compare incidence in vaccinated people during post-vaccination \nrisk interval vs. vaccinated people in a comparison window \n• If p\notential “statistical signal” detected, additional analyses and/or \nchart reviews conducted \n-System designed to be sensitive; not all detected signals \nrepresent a true safety concern \n18 \n        \n      \n                  \n  \n \n   \n  \n \n   \n   \n  \n  \n     Evaluation of Statistical Signals Detected for mRNA COVID-19 \nVaccines through VSD’s Rapid Cycle Analyses – 2020-2025 \n8 statistical signals detected \nAcute myocardial infarction \n Seizure \nAge 18+ years 18-64 years \nImmune Thrombocytopenic Purpura \nAge 65+ years \nVenous thromboembolism \nAge 12+ years Guillain-Barré syndrome \nAge 65+ years \nBell’s Palsy \nAge 12+ years \nIschemic stroke \nAge 50+ years \nMyocarditis \nAge 12+ years \nCOVID-19 Vaccine Safety Technical (VaST) Work Group: Enhancing vaccine safety monitoring during the pandemic – ScienceDirect and CDC unpublished data 19 \n        \n      \n                  \n  \n \n   \n  \n \n   \n   \n  \n  \n      \n \n \n  \n  \n \n  Evaluation of Statistical Signals Detected for mRNA COVID-19 \nVaccines through VSD’s Rapid Cycle Analyses – 2020-2025 \nAcute myocardial infarction \nAge 65+ years \nVenous thromboembolism \nAge 12+ years \nBell’s Palsy \nAge 12+ years \nIschemic stroke \nAge 50+ years \nGuillain-Barré syndrome \nAge 65+ years \nSeizure \n18-64 years \nImmune Thrombocytopenic Purpura \nAge 65+ years \nMyocarditis \nAge 12+ years 8 statistical signals detected Further investigations \nChart reviews \nTrend analysis \nAdditional studies \n(e.g., self-controlled \ncase series) \nQuery other \nsystems \nCOVID-19 Vaccine Safety Technical (VaST) Work Group: Enhancing vaccine safety monitoring during the pandemic – ScienceDirect and CDC unpublished data 20 \n        \n      \n                  \n  \n \n   \n  \n \n   \n   \n  \n  \n      \n \n \n  \n  \n \n      \n   \n      \n       Evaluation of Statistical Signals Detected for mRNA COVID-19 \nVaccines through VSD’s Rapid Cycle Analyses – 2020-2025 \nAcute myocardial infarction \nAge 65+ years \nVenous thromboembolism \nAge 12+ years \nBell’s Palsy \nAge 12+ years \nIschemic stroke \nAge 50+ years \nGuillain-Barré syndrome \nAge 65+ years \nSeizure \n18-64 years \nImmune Thrombocytopenic Purpura \nAge 65+ years \nMyocarditis \nAge 12+ years 8 statistical signals detected Further investigations \nsystem \nChart reviews \nTrend analysis \nAdditional studies \n(e.g., self-controlled \ncase series) \nQuery other \nCOVID-19 Vaccine Safety Technical (VaST) Work Group: Enhancing vaccine safety monitoring during the pandemic – ScienceDirect and CDC unpublished data \nIncreased risk for myocarditis \nfollowing mRNA COVID-19 vaccines \nNo clear or consistent evidence of \na safety concern for the others \nSafety assessment \n21 \n      \n        \n              \n  \n    \n               \n        \n  \n       \n    38\n6\n22Myocarditis Following mRNA COVID-19 Vaccination Among \nPeople Ages 12–39 Years in the Vaccine Safety Datalink \nIncidence of myocarditis within 7 days of vaccination per million mRNA vaccine doses administered \n* \n6 38 \n25 \n2 5 \n2 \nDose 1 \nOriginal monovalent Dose 2 \nOriginal monovalent Booster \nOriginal monovalent Bivalent \n2020-2021 2021-2022 2022-2023 2023-2024 2024-2025 * \nBackground \n<2 per million higher in males \n• Myocarditis rare in children aged <12 years \nand adults aged ≥50 years \n* • Rates peak at age 16-17 years and are \nrate \n*St\natistically significant increased rate ratio in vaccinated concurrent comparator analysis. Source: CDC Immunization Safety Office 22 \n        \n       \n                  \n                   \n                     Myocarditis and Pericarditis Following mRNA COVID-19 Vaccination in \nFDA’s Biologics Effectiveness and Safety System (BEST), 2023—2024 Season \nIncidence (cases per million doses) during days 1—7 following vaccine administration \nFDA issued Safety Labeling Change (SLC) notification letters to the manufacturers \non April 17, 2025, and initiated the SLC process to include new safety information on myocarditis and pericarditis for \nComirnaty and Spikevax. Under the labeling negotiations, FDA has notified sponsors of the above data \n2025 Safety and Availability Communications | FDA ; Information courtesy of FDA 23 \n      \n     \n              \n             \n       \n              \n \n           \n            \n            \n       \n                             \n        Follow-up CDC Studies Demonstrate Most Adolescents \nand Young Adults Have Recovered From Myocarditis \n• Surveys of individuals aged 12-29 years with myocarditis after mRNA COVID-19 vaccine, and their \nhealthcare providers, for whom a VAERS report was filed during January 12-November 5, 2021 \n• Based on cardiologist or other healthcare provider assessment: \n83% >90% \nFully or probably fully recovered by at Overall, fully or probably fully recovered by \nleas\nt 90 days after myocarditis onset at least a 1 year after myocarditis onset \n• Among patients with abnormal cardiac MRI at 1-year evaluation, most common abnormality was late ga\ndolinium enhancement \n-clinical significance unclear; majority considered recovered and cleared for all physical activity \n• No k\nnown deaths or cardiac transplants \nOutcomes at least 90 days since onset of myocarditis after mRNA COVID-19 vaccination in adolescents and young adults in the USA: a follow-up surveillance study - The Lancet Child & Adolescent \nHealth ; Outcomes at ≥1 year based on unpublished data 24 \n          \n             \n        \n             \n    \n            \n             \n    \n         \n          \n  \n                                         \n                                     \n                                      \n                              \n                     COVID-19 Vaccine Safety in Children Ages 6 Months to 11 Years \n• Risk of myocarditis following COVID-19 vaccines in children aged <12 years is low, \npar\nticularly for those aged 6 months to 5 years \n-Active, sequential analyses in the Vaccine Safety Datalink have demonstrated no statistical signals \nfor \nmyocarditis in children \n-No confirmed myocarditis cases in children aged <5 years in VAERS or VSD \n• Rapid cycle analyses in the VSD demonstrate no increased risks for 22 other pre -\nspecified outcomes following COVID-19 vaccination \n• Evaluations to assess multisystem inflammatory syndrome in children (MIS-C) following COVID-19 vaccination demonstrated that most patients had evidence of preceding SARS-CoV-2 infection \nSafety of COVID-19 Vaccination in United States Children Ages 5 to 11 Years | Pediatrics | American Academy of Pediatrics ; Safety Monitoring of mRNA COVID-19 Vaccine Third Doses Among Children Aged 6 Months–5 Years — United States, June 17, 2022–May 7, 2023 | \nMMWR ; COVID-19 Vaccine Safety First Year Findings in Adolescents | Pediatrics | American Academy of Pediatrics ; Safety Monitoring of Bivalent COVID-19 mRNA Vaccine Booster Doses Among Children Aged 5–11 Years — United States, October 12–January 1, 2023 | \nMMWR ; COVID-19 mRNA Vaccine Safety Among Children Aged 6 Months–5 Years — United States, June 18, 2022–August 21, 2022 | MMWR ; Safety of COVID-19 mRNA Vaccination Among Young Children in the Vaccine Safety Datalink | Pediatrics | American Academy of \nPediatrics ; Surveillance for Multisystem Inflammatory Syndrome in US Children Aged 5-11 Years Who Received Pfizer-BioNTech COVID-19 Vaccine, November 2021 through March 2022 – PubMed ; Reported cases of multisystem inflammatory syndrome in children aged \n12–20 years in the USA who received a COVID-19 vaccine, December, 2020, through August, 2021: a surveillance investigation - The Lancet Child & Adolescent Health 25 \n          \n        \n  \n                            \n          Majority of COVID-19 Vaccine Reports to VAERS in Children Aged \n<12 Years Include at Least One Vaccine Administration Error \nApproximately 77% of reports in children aged 6 months-4 years and 70% of reports in children aged 5-11 years \nrelated to administration errors between October 21, 2021 – April 30, 2025 \nData source: https://wonder.cdc.gov \nVAERS reports may include more than one administration error type 26 \n        \n \n    CDC Is Expanding Its Work to Prevent Vaccine \nAdministration Errors \nVaccine Administration Protocols | CDC 27 \nEvaluating Safety of COVID-19 Vaccines in Pregnant Women \n• >23,000 pregnant women CDC COVID-19 Vaccine Pregnancy Registry \n• 7 analyses \n• Ob\nservational studies based on survey \nand medical record information \n• >45,000 pregnant women Vaccine Safety Datalink \n• 11 an\nalyses to date \n• Cohort\n, case-control, and surveillance \nevaluations \n      \n \n     \n   \n    \n  \n           \n28 \n    \n       \n \n  \n \n  \n \n   \n  \n  \n  \n \n \n                                \n                               \n                                \n                              \n             COVID-19 Vaccine Safety During Pregnancy \nAcross CDC studies, evidence shows NO increased risk of: \nMaterna\nl outcomes Pregnancy outcomes Infant outcomes \n 25 medically-attended  Miscarriage  Major birth defects \nadverse events  Stillbirth  Neonatal ICU admission \n Serious adverse events  Preterm birth  Infant death \n Pregnancy-related  Small-for-gestational age \ncondi\ntions \n Maternal ICU admission \nEvaluation of Acute Adverse Events after Covid-19 Vaccination during Pregnancy | New England Journal of Medicine ; Receipt of COVID-19 Vaccine During Pregnancy and Preterm or Small-for-Gestational-Age at Birth — Eight Integrated Health Care \nOrganizations, United States, December 15, 2020–July 22, 2021 | MMWR ; Receipt of mRNA Covid-19 Vaccines and Risk of Spontaneous Abortion | New England Journal of Medicine ; Spontaneous Abortion Following COVID-19 Vaccination During \nPregnancy | Public Health | JAMA | JAMA Network ; COVID-19 Booster Vaccination in Early Pregnancy and Surveillance for Spontaneous Abortion; Coronavirus Disease 2019 (COVID-19) Vaccination and Stillbirth in the Vaccine Safety Datalink ; \nMedically Attended Acute Adverse Events in Pregnant Women ; Obstetric Complications and Birth Outcomes After Antenatal Coronavirus Disease 2019 (COVID-19) Vaccination; COVID-19 Vaccination in the First Trimester and Major Structural Birth \nDefects Among Live Births ; Accumulating Robust Evidence for Reducing Vaccine Hesitancy in Early Pregnancy—Reply 29 \n        \n   \n  \n        \n  \n  \n       \n      \n    \n       \n  \n        \n    \n            \n                   \n                     \n       \n   \n       \n       \n      Address Vaccine Safety \nTinnitus \n• Conducted data mining to assess tinnitus: \n-VAERS empirical Bayesian data mining did not find \ndisproportionate reporting of tinnitus \n-VSD tree-based data mining found no signals for tinnitus \n• Taken together, findings do not support an \ninc\nreased risk of tinnitus after COVID-19 vaccine \nPostmenopausal Bleeding After Coronavirus Disease 2019 (COVID-19) Vaccination: Vaccine Adverse Event Reporting System – PubMed \nMenstrual irregularities and vaginal bleeding after COVID-19 vaccination reported to v-safe active surveillance, USA in December, 2020-January, 2022: an observational cohort study – PubMed Tinnitus after COVID-19 vaccination: Findings from the vaccine adverse event reporting system and the vaccine safety datalink - ScienceDirect Examples of CDC Studies to \nConcerns from the Public \nAbnormal uterine bleeding \n• Conducted studies in VAERS, VSD, and v-safe for \nab\nnormal uterine bleeding \n• VSD studies demonstrated: \n-Availability of COVID-19 vaccines was not associated \nwith a change in incidence of medically-attended \nabnormal uterine or post-menopausal bleeding \n-Receipt of COVID-19 vaccine not associated with \ngreater bleeding severity \nAbnormal uterine bleeding diagnoses and care following COVID-19 vaccination – ScienceDirect \nPostmenopausal bleeding after COVID-19 vaccination – PubMed \n30 \n       \n   \n            \n  \n         \n          \n           \n             \n \n         \n            \n   \n            Safety Monitoring of Death Reports Following mRNA COVID -\n19 Vaccination in VAERS \n• As of May 30, 2025, there have been 19,417 domestic deaths reported to VAERS \nafter COVID-19 vaccination \n• Important considerations related to evaluation of death reports in VAERS \n-FDA Emergency Use Authorizations and CDC COVID-19 Vaccination Provider Enrollment \nAgreements required healthcare provider to report all deaths following COVID-19 vaccination to \nVAERS, regardless of cause or circumstances surrounding death (requirement does not apply to \noth\ner vaccines) \n-VAERS generally cannot assess causality of adverse reports, including deaths \n• We conducted an evaluation of deaths following mRNA COVID-19 vaccination in VAERS \nthr\nough January 31, 2023 \nVaccine Adverse Event Reporting System. VAERS Reporting Information for COVID-19 Vaccines. https://vaers.hhs.gov/reportevent.html 31 \n   \n    \n      \n \n  \n  \n         \n   \n              \n        \n   \n     \n  \n     \n \n                  \n                                \n Safety Monitoring of Death Reports Following mRNA*COVID-19 \nVaccination in VAERS – December 22, 2020 – January 31, 2023 \nDeaths reported in VAERS \nCDC requests \nmedical records \nExcluded \n12,849 wi\nth cause of death : • 1,790 re\nports of vaccine types 17,631 do\nmestic VAERS 17,579 re\nports with verified death after • Autopsy: 673 othe\nr than mRNA repo\nrts of death following review by CDC clinician • Death certification: 8,862 • 2,940 wi\nthout cause of death COVI\nD-19 vaccine • Medical records: 2,576 (52 de\ntermined not to be a death) info\nrmation available • VAER\nS report alone: 738 \n* Includes reports with missing vaccine type, but excludes reports known to be after Janssen or Novavax COVID-19 vaccine \nReports to the Vaccine Adverse Event Reporting System (VAERS) reviewed and processed during December 22, 2020 — January 31, 2023; reported date of vaccination during December 22, 2020 — January 31, 2023 or missing 32 \n   \n    \n      \n \n  \n  \n         \n   \n        \n \n     \n      \n          \n        \n    \n      \n     \n  \n     \n \n     \n                  \n                              Safety Monitoring of Death Reports Following mRNA*COVID-19 \nVaccination in VAERS – December 22, 2020 – January 31, 2023 \n17,631 domestic VAERS \nreports of death following \nCOVID-19 vaccine \n12,849 with cause of death : \n• Autopsy: 673 \n• Death certification: 8,862 \n• Medical records: 2,576 \n• VAERS report alone: 738 17,579 reports with verified death after \nreview by CDC clinician \n(52 determined not to be a death) \nCDC requests \nmedical records \nNational Center for Health Statistics \nMultiple Cause of Death Database \nDeath certificates \nfrom U.S. residents \nCause of death categorized \nby ICD-10 diagnostic codes Deaths reported in VAERS \n• 1,790 reports of vaccine types \nother than mRNA \n• 2,940 without cause of death information available Ex\ncluded \nDeaths reported in general U.S. population \n* Includes reports with missing vaccine type, but excludes reports known to be after Janssen or Novavax COVID-19 vaccine \nRep\norts to the Vaccine Adverse Event Reporting System (VAERS) reviewed and processed during December 22, 2020 — January 31, 2023; reported date of vaccination during December 22, 2020 — January 31, 2023 or missing 33 \n   \n    \n      \n \n  \n  \n         \n   \n      \n     \n      \n         \n        \n    \n      \n \n   \n  \n    \n \n   \n    \n         \n  \n     \n \n     \n                  \n                              \n                                    \n Safety Monitoring of Death Reports Following mRNA*COVID-19 \nVaccination in VAERS – December 22, 2020 – January 31, 2023 \n17,631 domestic VAERS \nreports of death following \nCOVID-19 vaccine 12,849 with cause of death : \n• Autopsy: 673 \n• Death certification: 8,862 \n• Medical records: 2,576 \n• VAERS report alone: 738 17,579 reports with verified death after \nreview by CDC clinician \n(52 determined not to be a death) \nNational Center for Health Statistics \nMultiple Cause of Death Database Death certificates \nfrom U.S. residents Cause of death categorized \nby ICD-10 diagnostic codes Deaths reported in VAERS \nObserved Rate \nNumber of deaths (cause-specific) \n100,000 persons vaccinated \nWithin 42 days of vaccination \nExpected Rate \nNumber of deaths (cause-specific) \n100,000 persons in U.S. population \nWithin 42 days of vaccination • 1,790 reports of vaccine types \nother than mRNA \n• 2,940 without cause of death information available Exclud\ned \nDeaths reported in general U.S. population \n* Includes reports with missing vaccine type, but excludes reports known to be after Janssen or Novavax COVID-19 vaccine \nReports to the Vaccine Adverse Event Reporting System (VAERS) reviewed and processed during December 22, 2020 — January 31, 2023; reported date of vaccination during December 22, 2020 — January 31, 2023 or missing Abara WE, et al. Expected Rates of Select Adverse Events After Immunization for Coronavirus Disease 2019 Vaccine Safety Monitoring | The Journal of Infectious Diseases ; Mahaux O, et al. Pharmacoepidemiological considerations in observed\n‐to‐expected analyses for vaccines \nCDC requests \nmedical records \n34 \n         \n        \n                     \n         \n     \n     \n    \n                 \n                             \n                              \n                                   \n                                \n          Reporting Rates of Death After mRNA*COVID-19 Vaccination Were Below \nBackground Rates of Death in the General U.S. Population \nThe most common causes of death reported to VAERS are consistent with the leading causes of death in the U.S. population \n0 0.2 0.4 0.6 0.8 1 Observed/Expected Ratio 6 months-17 years 18-49 years 50-64 years 65+ years Observed / Expected <1: Indicates \nlower observed death rate than \nthe expected rate within the post-\nvaccination interval of 42 days \n* Includes reports with missing vaccine type, but excludes reports known to be after Janssen or Novavax COVID-19 vaccine \nReports to the Vaccine Adverse Event Reporting System (VAERS) reviewed and processed during December 22, 2020 — January 31, 2023; reported date of vaccination during December 22, 2020 — January 31, 2023 or missing \nHoyert DL, Xu J. Deaths: preliminary data for 2011. Natl Vital Stat Rep. 2012; 61:1–51 ; U.S. Centers for Disease Control and Prevention. CDC WONDER. Available at https://wonder.cdc.gov/controller/datarequest/D157 Accessed March 20, 2025 \nAbara WE, et al. Expected Rates of Select Adverse Events After Immunization for Coronavirus Disease 2019 Vaccine Safety Monitoring | The Journal of Infectious Diseases ; Mahaux O, et al. Pharmacoepidemiological considerations in observed ‐to‐expected analyses for vaccines \nNational Center for Health Statistics, National Vital Statistics System. Deaths: Leading Causes of Death for 2021. 73:4. Published April 8, 2024. https://www.cdc.gov/nchs/data/nvsr/nvsr73/nvsr73-04.pdf National Center for Health Statistics, National Vital Statistics System. Deaths: Leading \nCauses of Death for 2020. 72:13. Published December 5, 2023. https://www.cdc.gov/nchs/data/databriefs/db492-tables.pdf#4 35 \n        \n       \n  \n \n \n \n  \n \n \n \n  \n \n \n \n  \n \n \n \n      \n     \n  \n           \n       \n  \n \n \n \n  \n     \n     \n          \n              \n              \n    \n          \n       Data From CDC’s Vaccine Safety Datalink Shows No \nIncreased Risk of Death Following mRNA COVID-19 Vaccines \n36 0.2 0.4 0.6 0.8 1 0.2 0.4 0.6 0.8 1 \n0.2 0.4 0.6 0.8 1 0.2 0.4 0.6 0.8 1 Dose 1 Dose 2 \nNon-COVID-19 mortality \nAll-cause mortality Cardiac-related mortality \nNon-COVID-19 cardiac-related mortality \nNon-COVID-19 mortality \nAll-cause mortality Cardiac-related mortality \nNon-COVID-19 cardiac-related mortality \nNon-COVID-19 mortality \nAll-cause mortality Cardiac-related mortality \nNon-COVID-19 cardiac-related mortality \nNon-COVID-19 mortality \nAll-cause mortality Cardiac-related mortality \nNon-COVID-19 cardiac-related mortality Pfizer-BioNTech \nModerna Ages 12 Years and Older \nAges 65 Years and Older (Medicare Beneficiaries) \nDose 1 Dose 2 \nX axis: Relative Incidence and 95% Confidence Intervals Pfizer-BioNTech \nModerna •2 self-controlled case series\nevaluations\n•No increased risk in the 28 days\nafter vaccination of:\n-Non-COVID mortality\n-All-cause mortality\n-Cardiac-related mortality\n-Non-COVID cardiac-related mortality\n•Similar findings in VSD cohort\nstudy of people ages 12+ years\nMortality risk after COVID-19 vaccination: A self-controlled case series study \nhttps://pubmed.ncbi.nlm.nih.gov/38388239/ \nA Modified Self-Controlled Case Series on Mortality Risk following Primary Series Doses of COVID-19 \nVaccines in U.S. Medicare Beneficiaries Aged 65 Years and Older - Acumen and Vaccine Safety Datalink, \nunpublished pending review at journal A safety study evaluating non-COVID-19 mortality risk following COVID-19 vaccination - PubMed \nData from December 14, 2020 through August 11, 2021  \n       \n   \n              \n               \n                       \n       \n       \n \n \n \n       \n \n    \n    \nTree-based data mining for safety assessment of first COVID-19 booster doses in the Vaccine Safety Datalink – PubMed \nSafety signal identification for COVID-19 bivalent booster vaccination using tree-based scan statistics in the Vaccine Safety Datalink - PubMed \n37 Using Data Mining to Assess for Unexpected \nEvents After COVID-19 Vaccination \n• >60,000 possible adverse events assessed in the \n70 day\ns after vaccination using tree-based data \nmining of ICD-10 codes in the VSD for: \n-Primary series \n-Initial booster \n-Bivalent booster \n• No new safety concerns identified outside of \nknown e\nvents \n-E.g., myocarditis/pericarditis, allergic reactions, \ncommon local and systemic reactions \nA broad assessment of covid-19 vaccine safety using tree-based data-mining in the vaccine safety datalink - PubMed \nSummary \n38 \n38 \n       \n \n   \n  \n \n    \n \n    \n   \n            \n        \n     CDC Summary: Adverse Events Associated with mRNA \nCOVID-19 Vaccines \nOccur with any vaccines: Occur with COVID-19 vaccines: \n• Local reactions • Myocarditis and pericarditis \n• S\nystemic reactions \n• Acute allergic reactions (e.g., anaphylaxis) \n• Syncope (fainting) \n• Shoulder injuries \nCDC evaluated at least 65 specific safety outcomes, conducted data mining of \n>60,000 potential outcomes for unexpected concerns, investigated numerous \nsignals, and conducted many epidemiologic studies \n39 \n     \n    \n      \n \n        \n     \n     \n      \n     \n                \n   \n40 NASEM Consensus Report on Adverse \nEffects of COVID-19 Vaccines – 2024 \n• Commissioned by Health Resources and Services \nAdministration (HRSA) \n• Reviewed nearly 600 studies on safety of COVID-19 vaccines \n• Concluded evidence supported causal association between mRNA COVID-19 vaccines and myocarditis \n-Evidence favors rejection of causal relationship \nbetween vaccination and 6 additional outcomes \nFront Matter | Evidence Review of the Adverse Effects of COVID-19 Vaccination and Intramuscular Vaccine Administration | \nThe National Academies Press \n        \n      \n           \n \n            \n         \n             \n    \n        COVID-19 Vaccines Have Been Evaluated Under the Most \nExtensive Safety Monitoring Program in U.S. History \n• Safety surveillance identified and characterized the risk of myocarditis after mRNA \nCOVID-19 vaccination \n• No other risks confirmed in the current U.S.-licensed vaccines except those seen with other vaccines (e.g., local and systemic reactions, allergic reactions) \n• CDC continues to prioritize the monitoring of COVID-19 vaccine safety, with at least 30 ongoing studies or activities \n• CDC continues to monitor the safety of COVID-19 vaccines \n41", "summary": "Update on CDC’s COVID-19 Vaccine Safety Monitoring  Sarah Meyer, MD MPH  Director, CDC’s Immunization Safety Office  June 25, 2025  1                                                                  Key Points  • CDC and interagency partners launched an extensive vaccine safety monitoring  program for COVID-19 vaccines  • Many potential safety outcomes were rigorously assessed through complementary passive and active systems  • Myocarditis is causally associated with mRNA COVID-19 vaccines …", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-25-26-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-06-25-26/04-Meyer-COVID-508.pdf", "doc_date": "2025-06-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 41}
{"title": "05 Peacock COVID 508", "content": "COVID- 19 Vaccination ImplementationNational Center for Immunization and Respiratory Diseases\nJune 25, 2025Immunization Services Division\nCenters for Disease Control and Prevention\n•National Immunization Survey (NIS):\n-Random -digit -dial cellular telephone survey of adults age ≥18 years in the U.S. (all \n50 states, 5 local jurisdictions, and territories); all responses are self reported.\n-Sample size: ~15,000 adult respondents weekly, ~60,000 adult respondents monthly\n-Data are weighted to represent the non- institutionalized U.S. population\n•Immunization Information Systems (IISs): \n-Confidential, population- based databases that record all vaccine doses administered \nby participating providers in a specific geographic area\n-ISD receives monthly aggregate data for COVID, influenza, and RSV, and quarterly \nline-level, de -identified data for individual immunizations\n•Vaccine Safety Datalink: \n-Estimates of vaccination coverage are based on electronic health data from multiple integrated health systemsData sources used to estimate U.S. immunization \ncoverage\nCOVID -19 Vaccination Coverage\nNational Immunization Survey -Fall Respiratory Virus Module\n0.020.040.060.08\n0.0\n9/7/2024\n9/14/2024\n9/21/20249/28/202410/5/2024\n10/12/2024\n10/19/2024\n10/26/2024\n11/2/202411/9/2024\n11/16/2024\n11/23/2024\n11/30/2024\n12/7/2024\n12/14/2024\n12/21/2024\n12/28/2024\n1/4/2025\n1/11/20251/18/20251/25/2025\n2/1/20252/8/2025\n2/15/20252/22/2025\n3/1/20253/8/2025\n3/15/20253/22/20253/29/2025\n4/5/2025\n4/12/20254/19/20254/26/2025Vaccination coverage (%)\nWeek ending date≥1 dose (65+)\n≥1 dose (18+)COVID -19 V accination Coverage (≥1 Dose) Among Adults 18 Years and Older \nand 65 Years and Older , 2024- 2025\nNational Immunization Survey -Fall Respiratory Virus Module\n44.1\n23.0\n0255075100\nSep 7\nSep 14\nSep 21Sep 28\nOct 5\nOct 12Oct 19Oct 26\nNov 2Nov 9\nNov 16Nov 23Nov 30\nDec 7\nDec 14Dec 21Dec 28\nJan 4\nJan 11Jan 18Jan 25\nFeb 1Feb 8\nFeb 15Feb 22\nMar 1Mar 8\nMar 15Mar 22Mar 29\nApr 5\nApr 12Apr 19Apr 26\nSep 7\nSep 14Sep 21Sep 28\nOct 5\nOct 12Oct 19Oct 26\nNov 2Nov 9\nNov 16Nov 23Nov 30\nDec 7\nDec 14Dec 21Dec 28\nJan 4\nJan 11Jan 18Jan 25\nFeb 1Feb 8\nFeb 15Feb 22\nMar 1Mar 8\nMar 15Mar 22Mar 29\nApr 5\nApr 12Apr 19Apr 26\nSep 7\nSep 14Sep 21Sep 28\nOct 5\nOct 12Oct 19Oct 26\nNov 2Nov 9\nNov 16Nov 23Nov 30\nDec 7\nDec 14Dec 21Dec 28\nJan 4\nJan 11Jan 18Jan 25\nFeb 1Feb 8\nFeb 15Feb 22\nMar 1Mar 8\nMar 15Mar 22Mar 29\nApr 5\nApr 12Apr 19Apr 26≥18 years 65-74 years ≥75 yearsVaccination coverage (%)\n2024- 25 season week ending dateVaccination coverage (2024-25) Vaccination coverage (2023-24)COVID -19 Vaccination Coverage Among Adults ≥18 Years, 65 -74 Years, \nand ≥75 Years, 2023 -24 and 2024 -25\nNational Immunization Survey -Fall Respiratory Virus Module\n23.0\n21.\n642.7\n37.946.5\n38.3\n0255075100Vaccination coverage (%)\nWeek ending dateOverall (6 months-17 years) 6 months-4 years 5-11 years 12-17 yearsCOVID -19 Vaccination Coverage* Among Children 6 Months –17 Years of \nAge, October 2024 –April 2025, NIS -Flu​\n* Up -to-date with the updated 2024 –25 COVID -19 vaccine is defined as receipt of at least one vaccination since August 22, 2024, for children ≥5 years; for children <5 years, up -to-\ndate status was defined based on the current recommendations that also take into account number of doses and brand of vaccine. Up- to-date status was determined by survey \nquestions on month and year of most recent COVID- 19 vaccine, and for children <5 years, total number of COVID -19 vaccinations re ceived and brand of most recent COVID- 19 \nvaccine.\nCOVID -19 V accination Coverage (≥2 Doses) Among Adults 18 Years and Older \nWho Are Immunocompromised Who Received First Dose in August/September \n2024, as of End of March 2025\nNational Immunization Survey -Fall Respiratory Virus Module\n*Immunocompromised a dults  were recommended to receive a second dose of 2024 -2025 COVID- 19 vaccine \nsix months after their first dose .2.416.60.81.49.98.1\n0.0 10.0 20.0 30.0 40.0 50.0 60.018-49 (n=85)50-64 (n=98)65+ (n=172)Male (n=95)Female (n=257)Overall 18+ immun\nocompromised\n(n=355)\nWeig\nhted % (95% CI)\n•COVID -19 vaccination coverage for older adults improved in 2024-2025 \ncompared to the previous season, but vaccination coverage for all adults > \n18 years was similar between the 2023-2024 and 2024-2025 seasons.\n•Approximately 13% of children between 6 months and 17 years of age \nwere up to date with COVID vaccination at the end of April 2025. Summary\nFor more information, contact CDC/ATSDR\n1-800- CDC- INFO (232- 4636)\nTTY:  1 -888- 232- 6348    www.cdc.gov           www.atsdr.cdc.gov \nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention and the Agency for Toxic Substances and Disease Registry.\nThank you", "summary": "COVID- 19 Vaccination ImplementationNational Center for Immunization and Respiratory Diseases June 25, 2025Immunization Services Division Centers for Disease Control and Prevention •National Immunization Survey (NIS): -Random -digit -dial cellular telephone survey of adults age ≥18 years in the U.S. (all  50 states, 5 local jurisdictions, and territories); all responses are self reported. -Sample size: ~15,000 adult respondents weekly, ~60,000 adult respondents monthly -Data are weighted to…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-25-26-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-06-25-26/05-Peacock-COVID-508.pdf", "doc_date": "2025-06-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 9}
{"title": "06 MacNeil COVID 508", "content": "Evidence to Recommendations (partial) for 2025 –2026 \nCOVID -19 Vaccination\nCoronavirus and Other Respiratory Viruses Division\nJune 25, 2025National Center for Immunization and Respiratory Diseases\n1\nEvidence to Recommendations ( EtR) Framework\nEtR Domain Question(s)\nPublic Health Problem •Is the problem of public health importance?\nBenefits and Harms•How substantial are the desirable anticipated effects?\n•How substantial are the undesirable anticipated effects?\n•Do the desirable effects outweigh the undesirable effects?\nValues•Does the target population feel the desirable effects are large relative \nto the undesirable effects?\n•Is there important variability in how patients value the outcome?\nAcceptability •Is the intervention acceptable to key stakeholders?\nFeasibility •Is the intervention feasible to implement?\nResource Use •Is the intervention a reasonable and efficient allocation of resources?\nEquity •What would be the impact of the intervention on health equity?\n•May 29th work group call\n-Public Health Problem domain of the Evidence to Recommendations ( EtR) \nFramework was presented\n•June 5th work group call\n-Benefits and Harms domain of the EtR was presented\n•June 12th planned work group call\n-Additional EtR domains were planned to be presented\n-Final work group polling not completed because call was not convenedWork Group Interpretations\n3\nSummary\nPublic Health Problem\n•Burden from COVID -19 has been trending down year over year since 2021, but \nsubstantial morbidity and mortality continues to occur.\n•Higher rates of COVID -19 hospitalization and deaths occur in the oldest and \nyoungest age groups.\n-Highest rates in adults ages ≥65 years and infants ages <6 months\n•Children ages <2 years have the highest morbidity and mortality of all pediatric ages, \nbut deaths due to COVID -19 can occur at any age.\n-Maternal vaccination is the best protection against COVID -19 for pregnant women \nand infants less than 6 months of age (who are too young to be vaccinated).\n•2024 –2025 COVID -19 vaccination is effective in preventing hospitalizations and critical \noutcomes from COVID -19 in adults.\n-Data from prior vaccine formulations show that vaccine effectiveness has been similar \nacross age groups.\n•COVID -19 vaccines have been continuously monitored through robust safety surveillance\n•Safety surveillance identified and characterized the risk of myocarditis and pericarditis \nafter mRNA COVID -19 vaccination.\n-No other risks confirmed in the current U.S. -licensed vaccines except those seen with \nother vaccines (e.g., local and systemic reactions, allergic reactions).\n•Pregnant women are at increased risk of severe disease and adverse pregnancy outcomes \nfrom COVID -19.\n•Maternal vaccination has been shown to protect infants <6 months of age from severe \noutcomes of COVID -19.Summary\nBenefits and Harms \nThank you to all the CDC and external collaborators who \ncontributed to these presentations.", "summary": "Evidence to Recommendations (partial) for 2025 –2026  COVID -19 Vaccination Coronavirus and Other Respiratory Viruses Division June 25, 2025National Center for Immunization and Respiratory Diseases 1 Evidence to Recommendations ( EtR) Framework EtR Domain Question(s) Public Health Problem •Is the problem of public health importance? Benefits and Harms•How substantial are the desirable anticipated effects? •How substantial are the undesirable anticipated effects? •Do the desirable effects…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-25-26-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-06-25-26/06-MacNeil-COVID-508.pdf", "doc_date": "2025-06-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 6}
{"title": "01 MacNeil Mat Peds RSV 508", "content": "Maternal/Pediatric Respiratory Syncytial Virus (RSV) \nSession\nAdvisory Committee on Immunization Practices Meeting\nJune 25, 2025\n1U.S. Centers for Disease Control and Prevention\nSession Introduction\n•RSV can infect the small airways in the lungs, \nparticularly in infants\n•Most (68%) infants are infected in the first year of \nlife and nearly all (97%) by age 2 years2\n•2-3% of young infants are hospitalized for RSV3,4,5\n-~80% of children hospitalized with RSV age <2 years \nhave no underlying medical conditions3\n•Prior to 2023, no long -acting* products were \navailable for the prevention of severe RSV disease\n*Long -acting is defined as any product that requires one dose to provide protection during an RSV season\nReferences: 1) Suh et al, JID (2022): https://doi.org/10.1093/infdis/jiac120  2) Glezen  et al, Arch Dis Child (1986): https://doi.org/10.1001/archpedi.1986.02140200053026  3) Hall \net al, Pediatrics (2013): https://doi.org/10.1542/peds.2013 -0303  4) Langley et al, PIDJ (2011): https://doi.org/10.1097/INF.0b013e3182184ae7  5) Curns et al, Pediatric s (2024): \nhttps://doi.org/10.1542/peds.2023 -062574RSV is the leading cause of hospitalization in U.S. infants1\nImage: Goncalves et al. Critical Care \nResearch and Practice 2012\n2\nIn 2023 two products were approved by FDA and subsequently \nrecommended by CDC and ACIP\nMaternal RSV \nvaccine\nAbrysvo, Pfizer  \n*Either  maternal RSV vaccine or nirsevimab is given to protect infants against severe RSV disease \n– only one is needed in most instances \nPregnant women 32 through \n36 weeks’ gestation\nAdminister September \nthrough January in most of \nthecontinental United \nStates†All infants ages <8 months* \nSecond season dose for children \nages 8 –19 months at increased \nrisk of severe RSV disease \nAdminister October through \nMarch in most of the continental \nUnited States†(as early as \npossible¥)\n† Timing of administration for RSV immunization may differ in jurisdictions with RSV seasonality that differs from most of th e continental United States; ¥ The optimal timing for nirsevimab \nadministration is shortly before the RSV season begins (e.g., October –November), or within a baby's first week of life if born O ctober through March (ideally during the birth hospitalization.)Nirsevimab\nBeyfortus , Sanofi & AstraZeneca \n3\nToday the committee will be considering a recommendation \nfor a newly FDA -approved product\nMaternal RSV \nvaccine\nAbrysvo, Pfizer  \n*Either  maternal RSV vaccine or an infant antibody is given to protect infants against severe RSV \ndisease – only one is needed in most instances \nPregnant women \n32 through 36 \nweeks’ gestation\nAdminister \nSeptember through \nJanuary in most of \nthecontinental \nUnited States†All infants ages <8 \nmonths* \nSecond season dose for \nchildren ages 8 –19 \nmonths at increased risk \nof severe RSV disease \nAdminister October \nthrough March in most of \nthe continental United \nStates † (as early as \npossible¥)Nirsevimab\nBeyfortus , Sanofi & \nAstraZeneca Clesrovimab\nEnflonasia , Merck\nApproved by FDA on \n6/9/2025\nAll infants ages <8 \nmonths* \nAdminister October \nthrough March in most of \nthe continental United \nStates † (as early as \npossible¥)\n† Timing of administration for RSV immunization may differ in jurisdictions with RSV seasonality that differs from most of th e continental United States; ¥ The optimal timing for nirsevimab \nadministration is shortly before the RSV season begins (e.g., October –November), or within a baby's first week of life if born O ctober through March (ideally during the birth hospitalization.)4\n•September 2024 : Maternal/pediatric RSV work group reviewed and discussed data from Merck on \nsafety and efficacy of clesrovimab \n•October 2024: ACIP reviewed and discussed data from Merck on safety and efficacy of clesrovimab \nand the maternal/pediatric work group’s interpretation of these data\n•November 2024 – April 2025: Maternal/Pediatric RSV work group reviewed and discussed\n-GRADE1,2 (Grading of Recommendations, Assessment, Development, and Evaluations) for \nclesrovimab \n-Evidence to Recommendation Framework2 for clesrovimab\n•April 2025: ACIP reviewed and discussed the Evidence to Recommendation Framework and GRADE \nfor clesrovimab\n•June 2025 (Today): ACIP will be presented with recap of the Evidence to Recommendations \nFramework and vote on clesrovimabTimeline of work group and ACIP review of clesrovimab \nReferences : 1) Ahmed et al, Vaccine (2011 ): https://doi.org/10.1016/j.vaccine.2011.08.005  2) Lee et al, MMRW (2018): https://www.cdc.gov/mmwr/volumes/67/wr/mm6745a4.htm  5\n•April – June 2025: The work group reviewed data on uptake, safety, and \neffectiveness of maternal RSV vaccine and long -acting monoclonal antibody \nfrom the 2024 -2025 season\n•June 2025 (Today): ACIP will be presented with these data as well as the \nwork group interpretationAdditional data reviewed by the work group since the \nApril 2025 ACIP meeting \n6\n•Updates on administration and uptake of maternal RSV vaccine and long -acting \nmonoclonal antibody — Dr. Georgina Peacock (CDC/NCIRD)\n•Updates on effectiveness and impact of maternal RSV vaccine and long -acting monoclonal \nantibody — Dr. Adam MacNeil (CDC/NCIRD)\n•Safety of maternal RSV vaccine and long -acting monoclonal antibody — Dr. Malini DeSilva \n(HealthPartners Institute) & Dr. Matthew F. Daley (Kaiser Permanente Institute for Health \nResearch)\n•Evidence to Recommendation Framework: Clesrovimab — Dr. Adam MacNeil (CDC/NCIRD)\n•Clinical considerations and work group interpretation — Dr. Adam MacNeil (CDC/NCIRD)Today’s agenda: June 25, 2025\n7\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position \nof the U.S. Centers for Disease Control and Prevention.\nThank you", "summary": "Maternal/Pediatric Respiratory Syncytial Virus (RSV)  Session Advisory Committee on Immunization Practices Meeting June 25, 2025 1U.S. Centers for Disease Control and Prevention Session Introduction •RSV can infect the small airways in the lungs,  particularly in infants •Most (68%) infants are infected in the first year of  life and nearly all (97%) by age 2 years2 •2-3% of young infants are hospitalized for RSV3,4,5 -~80% of children hospitalized with RSV age <2 years  have no underlying…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-25-26-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-06-25-26/01-MacNeil-Mat-Peds-RSV-508.pdf", "doc_date": "2025-06-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 8}
{"title": "02 Peacock Mat Peds RSV 508", "content": "Implementation and Uptake of Nirsevimab and \nMaternal Vaccine for Infant Protection from RSV\nImmunization Services Division\nCenters for Disease Control and Prevention\nJune 25, 2025National Center for Immunization and Respiratory Diseases\n\n•National Immunization Survey (NIS):\n-Random -digit -dial cellular telephone survey of adults age ≥18 years in the U.S. (all \n50 states, 5 local jurisdictions, and territories); all responses are self reported.\n-Sample size: ~15,000 adult respondents weekly, ~60,000 adult respondents monthly\n-Data are weighted to represent the non- institutionalized U.S. population\n•Immunization Information Systems (IISs): \n-Confidential, population- based databases that record all vaccine doses administered \nby participating providers in a specific geographic area\n-ISD receives monthly aggregate data for COVID, influenza, and RSV, and quarterly \nline-level, de -identified data for individual immunizations\n•Vaccine Safety Datalink: \n-Estimates of vaccination coverage are based on electronic health data from multiple integrated health systemsData sources used to estimate U.S. immunization \ncoverage\nCoverage for Nirsevimab and Maternal \nVaccination\nNumber of infants <8 months old who received nirsevimab+, by month of receipt, \nIIS data from 36 U.S. jurisdictions, October 2023– December 2024*\n050000100000150000200000250000300000350000\nOct-23 Nov-23 Dec-23 Jan-24 Feb-24 Mar-24 Apr-24 May-24 Jun-24 Jul-24 Aug-24 Sep-24 Oct-24 Nov-24 Dec-24No. of infants\nMonth of nirsevimab receipt\n+Includes infants <8 months of age who received ≥1 dose of nirsevimab prior to January 1, 2025.​\n*Preliminary IIS data through 12/31/24 from 36 U.S. jurisdictions (AK, AR, AZ, CA, CT, DC, DE, FL, IL, IA, KY, LA, MD, ME, MI,  MN, MO, MS, MT, NJ, NM, NV, NY, OH, OK, PA, SD, TN, TX, VT, WA, WI, WV, WY, NYC, Philadelphia).​\n0 10000 20000 30000 40000 50000 60000Apr-23\nMay-23\nJun-23\nJul-23\nAug-23\nSep-23\nOct-23\nNov-23\nDec-23\nJan-24\nFeb-24\nMar-24\nNo. infants who received nirsevimabInfant birth monthInfant age at nirsevimab receipt, by birth month \nApr2023─Mar2024* \n0-3 days\n4-6 days\n7d-<1mo\n>=1moAge at \nnirsevimab \nreceipt\n*Preliminary IIS data through 12/31/24 from 36 U.S. jurisdictions (AK, AR, AZ, CA, CT, DC, DE, FL, IL, IA, KY, LA, MD, ME, MI,  MN, MO, MS, MT, NJ, NM, NV, NY, OH, OK, PA, SD, TN, TX, VT, WA, WI, WV, WY, NYC, Philadelphia).​\n0 20000 40000 60000 80000 100000Apr-24\nMay-24\nJun-24\nJul-24\nAug-24\nSep-24\nOct-24\nNov-24\nDec-24\nNo. infants who received nirsevimabInfant birth monthInfant age at nirsevimab receipt, by birth month \nApr2024─Dec2024* \n0-3 days\n4-6 days\n7d-<1mo\n>=1moAge at \nnirsevimab \nreceipt\n*Preliminary IIS data through 12/31/24 from 36 U.S. jurisdictions (AK, AR, AZ, CA, CT, DC, DE, FL, IL, IA, KY, LA, MD, ME, MI,  MN, MO, MS, MT, NJ, NM, NV, NY, OH, OK, PA, SD, TN, TX, VT, WA, WI, WV, WY, NYC, Philadelphia).​\nPercent of pregnant women ages 18 –49 years vaccinated with RSV vaccine \noverall and by race and ethnicity, Vaccine Safety Datalink, 2024 –25\n•38.5% of pregnant women were vaccinated overall\n•Vaccination coverage ranged from 25.7% among Black, Non -Hispanic (Black) \npregnant women to 52.6% among Asian, Non -Hispanic (Asian) pregnant \nwomen\nData source: Respiratory Syncytial Virus (RSV) Vaccination Coverage, Pregnant Women, United States | RSVVaxView  | CDC\n0.26.7 6.914.0 14.7 12.329.938.046.146.750.4\n44.7\n020406080100\nOct-24 (n=268) Nov-24 (n=401) Dec-24 (n=344) Jan-25 (n=336) Feb-25 (n=368) Mar-25 (n=653)PercentProtection against RSV with maternal vaccination or nirsevimab among infants <8 \nmonths* during the RSV season (born since April 2024), National Immunization Survey -\nFall Respiratory Virus Module\nData source: https://www.cdc.gov/rsvvaxview/dashboard/nirsevimab -coverage -infants.html  57% of infants born \nApril 2024- March 2025 \nwere protected from RSV by maternal vaccination or receipt \nof nirsevimab.\n*Born April 2024- March 2025\n\nBirthing Hospital Enrollment in VFC to \nFacilitate Nirsevimab  Administration\n•For infants born during October through March, nirsevimab should be \nadministered in the first week of life – ideally during the birth \nhospitalization.1\n•Children who lack commercial insurance coverage (~45%)2 are less likely to \nbe seen by their primary care provider (PCP) within one week of birth than \nare children who are commercially insured.\n•Birthing facilities and their staff are critical to ensuring newborns are protected against RSV before hospital discharge, including newborns who qualify for the Vaccines for Children (VFC) program.Protecting Newborns against RSV\n1. Use of Nirsevimab for the Prevention of Respiratory Syncytial Virus Disease Among Infants and Young Children: Recommendations  of the Advisory Committee on Immunization Practices \n— United States, 2023 | MMWR\n2. CDC National Center for Health Statistics: Health Insurance Coverage: Early Release of Estimates From the National Health Interview Survey, January –June 2024\n•Participation in the VFC Program:\n-Promotes equitable access to all ACIP -recommended vaccines\n-Enables newborns to receive the immunizations they need before hospital \ndischarge\n-Reduces hospital’s up -front costs\n•Hospitals do not pay for nirsevimab or hepatitis B vaccines for VFC -eligible \nchildren\n-Helps provide quality care to all infants who are at risk for RSV infection, regardless of insurance statusBenefits for Birthing Hospitals\n•2023\n-292 of 2,827 (10%) birthing hospitals were \nenrolled in VFC\n•Updated policy approaches, new partnerships, \nand communication\n•2025*ⴕ:\n-1,012 (36%) birthing hospitals are enrolled in VFC\n-Substantial increase over a two -year period \nbetween October 2023 and March 2025Birthing Hospital Enrollment in VFC\n*Data as of March 31,  2025\nⴕ  Data reported by the Provider Education Assessment and Reporting (PEAR) system\n•Supply\n-Anticipated to be sufficient to meet demand and to be available earlier than \nduring the 2024 -2025 season \n-Earlier supply (1) enables broad availability prior to the start of immunization, (2) promotes confidence in supply and program implementation.\n•Planning\n-CDC will facilitate equitable availability of RSV monoclonal antibody across jurisdictions \n-Pre-season technical assistance around ordering will be provided to jurisdictions\n•Increased availability of 50mg doses of nirsevimab  at the beginning of the season \nis anticipated.\n•Newly licensed clesrovimab can be available once it has been added to CDC's VFC \ncontracts.Supply and Ordering for RSV Monoclonal Antibody in \nthe VFC program:  2025- 2026 Season\n•In 2024-2025, more infants who were born during RSV season and \nreceived nirsevimab did so in the first month of life compared to those \nborn in the prior season of administration (2023-2024).\n•Maternal immunization and RSV monoclonal antibody protected 57% of \ninfants born April 2024-March 2025, showing the benefit of offering both \noptions. \n•Increased birthing hospital enrollment and improved early supply of RSV monoclonal antibody should provide greater access to protection from \nRSV in this upcoming season. Summary\nFor more information, contact CDC/ATSDR\n1-800- CDC- INFO (232- 4636)\nTTY:  1 -888- 232- 6348    www.cdc.gov           www.atsdr.cdc.gov \nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention and the Agency for Toxic Substances and Disease Registry.\nThank you", "summary": "Implementation and Uptake of Nirsevimab and  Maternal Vaccine for Infant Protection from RSV Immunization Services Division Centers for Disease Control and Prevention June 25, 2025National Center for Immunization and Respiratory Diseases  •National Immunization Survey (NIS): -Random -digit -dial cellular telephone survey of adults age ≥18 years in the U.S. (all  50 states, 5 local jurisdictions, and territories); all responses are self reported. -Sample size: ~15,000 adult respondents weekly,…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-25-26-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-06-25-26/02-Peacock-Mat-Peds-RSV-508.pdf", "doc_date": "2025-06-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 15}
{"title": "03 MacNeil Mat Peds RSV 508", "content": "Effectiveness and impact of RSV \nprevention products in infants during \nthe 2024 –2025 RSV season\nCoronavirus and Other Respiratory Viruses Division\nJune 25, 2025National Center for Immunization and Respiratory Diseases\n\nProduct Effectiveness (PE)\n•Summary of CDC systems used toevaluate PE\n•Effectiveness of nirsevimab and maternal RSV \nvaccine during the 2024 –2025 RSV season in \nthe U.S.\nRSV Hospitalization Rates and Product Impact \n•Summary of CDC systems used for monitoring \nRSV hospitalization rates\n•Impact of nirsevimab and maternal RSV \nvaccine during the 2024 –2025 RSV season in \nthe U.S.Agenda\n2\nProduct effectiveness \nmethods and CDC \nsystems used for \nevaluation\n3\nObservational VE studies Methods1\nVirtual SARS -CoV-2, Influenza, \nand Other respiratory viruses \nNetwork (VISION) Test-negative \ndesign2,3,4\nNew Vaccine Surveillance \nNetwork (NVSN)\nOvercoming Network \n(Overcoming)Matched Case -\nControl5Study designs for observational PE studies\nReferences for study design methods with relevant examples\n1Roper L, et. al. A framework for monitoring RSV prevention product effectiveness in the United States.  Vaccine  2025;45:126633\n2 Chua H, et. al. The Use of Test -negative Controls to Monitor Vaccine Effectiveness: A Systematic Review of Methodology. Epidemiology  2020;31:43 –64.\n3 Moline HL, et al. Respiratory Syncytial Virus Disease Burden and Nirsevimab  Effectiveness in Young Children From 2023 -2024..  JAMA Pediatr  2025;179:179 -187. \n4 Payne AB, et. al. Respiratory syncytial virus (RSV) vaccine effectiveness against RSV -associated hospitalisations  and emergency department encounters among adults aged 60 years and older in the USA, October,  2023, to March,  2024: a test -\nnegative design analysis.  Lancet  2024;404:1547 -1559.\n5 Zambrano LD, et. al. Durability of Original Monovalent mRNA Vaccine Effectiveness Against COVID -19 Omicron -Associated Hospitaliz ation in Children and Adolescents - United States, 2021 -2023.  MMWR  2024;73:330 -338Effectiveness = 1 – (odds ratio) x 100%    Odds ratio = 𝑂𝑑𝑑𝑠  𝑜𝑓 𝑖𝑚𝑚𝑢𝑛𝑖𝑧𝑎𝑡𝑖𝑜𝑛 𝑐𝑎𝑠𝑒𝑠\n𝑂𝑑𝑑𝑠  𝑜𝑓 𝑖𝑚𝑚𝑢𝑛𝑖𝑧𝑎𝑡𝑖𝑜𝑛 𝑐𝑜𝑛𝑡𝑟𝑜𝑙𝑠\n4Persons who seek care for \nRSV-like illness during \nRSV seasonCases\nTest positive for \nRSVImmunized\nUnimmunized\nControls \nTest negative for \nRSVImmunized\nUnimmunized\nCDC networks used to assess RSV product effectiveness \nin infants and children\nVISION\nMulti -site network of electronic \nhealth records (EHRs)\n160 emergency department (ED) \nand 131 hospitals in 6 states\nChildren visiting a participating ED \nor hospital with RSV -like illness are \neligible for inclusionNVSN\n \nActive surveillance for acute \nrespiratory illness (ARI) in children\n7 academic pediatric health \nsystems in 7 states\nChildren hospitalized or visiting the \nED for ARI are eligible for \nenrollmentOvercoming\nActive surveillance for pediatric RSV \nwith case -control design\n26 pediatric intensive care units \n(ICUs) in 23 states\nChildren in a participating ICU with \nARI are eligible for inclusion.\n5VISION: https://www.cdc.gov/flu -vaccines -work/php/vaccine -effectiveness/vision -network.html ; NVSN: https://www.cdc.gov/nvsn/php/about/index.html ; Overcoming: https://www.palisi.org/overcomecovid   \n; \nSummary of CDC networks used to assess RSV product \neffectiveness in children\nVISION NVSN Overcoming\nInfant and maternal \nimmunization dataElectronic health records, state \nand city registries, and claims \ndata (subset of sites)Electronic health records, state \nregistries, out -of-network \nprovider records, parent reportElectronic health records, \nstate registries, provider \nrecords, parent report\nAnalytic study period October 2024 –March 2025 October 2024 –March 2025 December 2024 –April 2025\nCases RSV-like illness (RLI) with \nclinical positive RSV antigen or \nnucleic acid amplification test \n(NAAT)Acute respiratory illness (ARI) \nwith RSV detected on \nsystematic NAAT testingARI with clinical positive \nRSV antigen or NAAT\nControls RSV-like illness with negative \nRSV NAATAcute respiratory illness (ARI) \nwith no RSV detected on \nsystematic NAAT testingARI with negative NAAT; \nCase -matched on site, age, \nand date of hospitalization\n6\nSummary of VISION, NVSN, and Overcoming analytic \nmethods used to assess product effectiveness in children\nVISION NVSN Overcoming\nNirsevimab\nanalytic populationInfants <8 months as of October 1, 2024, or born after October 1, 2024  with no maternal RSV \nvaccination receipt\nMaternal vaccine \nanalytic populationInfants born on or after \nSeptember 14, 2024  who did not \nreceive nirsevimabInfants <6 months of age during \nthe study period who did not \nreceive nirsevimabNot assessed\nAnalysis Multivariable logistic regression \nmodels, adjusting for site, age in \nmonths, calendar date, race and \nethnicity, and sex. \nModels adjusting for underlying \nmedical conditions did not \nmeaningfully change estimates.Multivariable logistic regression \nmodels, adjusting for site, age in \nmonths, and month of enrollment. \nNirsevimab analysis adjusted for \npresence of ≥1 high -risk medical \ncondition for severe RSV \ndisease; maternal RSV analysis \nadjusted for race/ethnicity and \ninsurance status.Multivariable logistic \nregression models, adjusting \nfor site, age in months, \ntiming of enrollment, \npresence of ≥1 underlying \nmedical condition, and social \nvulnerability index.\nOutcomes assessed Hospitalization, emergency \ndepartment (ED) visit, intensive \ncare unit (ICU) admissionHospitalization, ED visit, ICU \nadmissionICU admission\n7\nNirsevimab \neffectiveness \nduring the \n2024–2025 \nRSV season in \nthe United States\n8\nNirsevimab product effectiveness (PE) against RSV -associated emergency department \n(ED) visits  among infants in their first RSV season, VISION & NVSN, 2024 –2025\n*VISION analysis included children who received nirsevimab  ≥7 days prior to encounter.\n†Product effectiveness (PE) calculated as (1 -adjusted odds ratio)*100, with adjusted odds ratio estimated using multivariable log istic regression model, adjusting for site, age in months, calendar \ndate, race and ethnicity, and sex.\n‡NVSN analysis included children who received nirsevimab  ≥7 days prior to symptom onset. \n§Product effectiveness (PE) calculated as (1 -adjusted odds ratio)*100, with adjusted odds ratio estimated using multivariable log istic regression model, adjusting for site, age in months, month of \nenrollment, and presence of >1 high-risk medical condition for severe RSV disease. \nIQR: Interquartile Range | CI: Confidence IntervalNirsevimab was effective against RSV -associated ED visits.SYSTEM \nNirsevimab StatusRSV-positive \nencounters\nN (Col %)RSV-negative \nencounters\nN (Col %)Median days \nsince dose \n(IQR)Adjusted \nPE (95% CI)\nVISION1225 2833\nNo nirsevimab  doses966 (79) 1799 (64)Not Applicable Reference\nNirsevimab, ≥7 days prior*259 (21) 1034 (36) 68 (37 -102) 63 (56 -69)†\nNVSN 107 381\nNo nirsevimab  doses92 (86) 214 (56)Not Applicable Reference\nNirsevimab, ≥7 days prior‡15 (14) 167 (44) 68 (41 -103) 76 (55 -87)§\n0 50 100\nProduct Effectiveness (%)\n9\nNirsevimab product effectiveness (PE) against RSV -associated hospitalization  \namong infants in their first RSV season, VISION & NVSN, 2024 –2025\nSYSTEM \nNirsevimab StatusRSV-positive \nencounters\nN (Col %)RSV-negative \nencounters\nN (Col %)Median days \nsince dose \n(IQR)Adjusted \nPE (95% CI)\nVISION286 318\nNo nirsevimab  doses233 (81) 174 (55)Not Applicable Reference\nNirsevimab, ≥7 days prior*53 (19) 144 (45) 61 (27 -102) 79 (67 -87)†\nNVSN 294 378\nNo nirsevimab  doses263 (89) 229 (61)Not Applicable Reference\nNirsevimab, ≥7 days prior‡31 (11) 149 (39) 52 (27 -87) 82 (71 -88)§\nNirsevimab was effective against RSV -associated hospitalization.0 20 40 60 80 100\nProduct Effectiveness (%)\n*VISION analysis included children who received nirsevimab  ≥7 days prior to encounter.\n†Product effectiveness (PE) calculated as (1 -adjusted odds ratio)*100, with adjusted odds ratio estimated using multivariable log istic regression model, adjusting for site, age in months, calendar \ndate, race and ethnicity, and sex.\n‡NVSN analysis included children who received nirsevimab  ≥7 days prior to symptom onset. \n§Product effectiveness (PE) calculated as (1 -adjusted odds ratio)*100, with adjusted odds ratio estimated using multivariable log istic regression model, adjusting for site, age in months, month of \nenrollment, and presence of >1 high-risk medical condition for severe RSV disease. 10\nNirsevimab product effectiveness (PE) against RSV -associated intensive care unit \n(ICU) admission among infants in their first RSV season, VISION, NVSN & \nOvercoming, 2024 –2025\nSYSTEM \nNirsevimab StatusRSV-positive \nencounters\nN (Col %)RSV-negative \nencounters\nN (Col %)Median days \nsince dose \n(IQR)Adjusted \nPE (95% CI)\nVISION 56 318\nNo nirsevimab  doses 48 (86) 174 (55) Not Applicable Reference\nNirsevimab, ≥7 days prior*8 (14) 144 (45) 56 (25 -97) 82 (57 -93)†\nNVSN 73 71\nNo nirsevimab  doses 67 (92) 40 (56) Not Applicable Reference\nNirsevimab, ≥7 days prior‡6 (8) 31 (44) 52 (24 -84) 88 (63 -96)§\nOvercoming 409 263\nNo nirsevimab  doses 354 (87) 146 (56) Not Applicable Reference\nNirsevimab, ≥7 days prior* 55 (13) 117 (44) 50 (32 -86) 80 (73 -85)¶\nNirsevimab  was effective against RSV -associated ICU admission.0 20 40 60 80 100\nProduct Effectiveness (%)\n*Analysis included children who received nirsevimab  ≥7 days prior to encounter.\n†Product effectiveness (PE) calculated as (1 -adjusted odds ratio)*100, with adjusted odds ratio estimated using multivariable log istic regression model, adjusting for site, age in months, calendar \ndate, race and ethnicity, and sex.  RSV -negative encounters were those among children hospitalized for RSV -like illness and not limited to children admitted to the ICU.\n‡NVSN analysis included children who received nirsevimab  ≥7 days prior to symptom onset. \n§Product effectiveness (PE) calculated as (1 -adjusted odds ratio)*100, with adjusted odds ratio estimated using multivariable log istic regression model, adjusting for site, age in months, month of \nenrollment, and presence of  >1 high-risk medical condition for severe RSV disease. \n¶Product effectiveness (PE) calculated as (1 -adjusted odds ratio)*100, with adjusted odds ratio estimated using multivariable log istic regression model, adjusting for age in months, timing of \nadmission, census region, presence of ≥1 underlying medical condition, and social vulnerability index. Hospital site included  as a repeated measure. The analysis was not limited to matched pairs. 11\nMaternal vaccine effectiveness during \nthe 2024–2025 RSV season in the \nUnited States12\nMaternal vaccine effectiveness (VE) against RSV -associated emergency \ndepartment (ED) visits  among infants in their first RSV season, VISION, 2024 –2025\nSYSTEM \nNirsevimab StatusRSV-\npositive \nencounters\nN (Col %)RSV-negative \nencounters\nN (Col %)Median days \nsince birth (IQR)Median days \nsince dose \n(IQR)Adjusted \nVE (95% CI)\nVISION333 660\nNo maternal \nvaccine262 (79) 428 (65) Not Applicable Not Applicable Reference\nMaternal vaccine* 71 (21) 232 (35) 53 (31 -90) 85 (65 -110) 54 (35 -67)†\nMaternal RSV vaccine was effective against\nRSV-associated ED visits in infants.0 20 40 60 80 100\nVaccine Effectiveness (%)\n*VISION analysis included children who were born ≥14 days after maternal RSV vaccine dose.\n†Vaccine effectiveness (VE) calculated as (1 -adjusted odds ratio)*100, with adjusted odds ratio estimated using multivariable log istic regression model, adjusting for site, age in months, calendar \ndate, race and ethnicity, and sex.\nIQR: Interquartile Range | CI: Confidence Interval 13\nSYSTEM \nVaccination StatusRSV-positive \nencounters\nN (Col %)RSV-negative \nencounters\nN (Col %)Median days since \nbirth (IQR)Median days \nsince dose \n(IQR)Adjusted \nVE (95% CI)\nVISION 134 122\nNo maternal vaccine 109 (81) 77 (63) Not Applicable Not Applicable Reference\nMaternal vaccine* 25 (19) 45 (37) 35 (17 -69) 73 (52 -111) 79 (55 -90)†\nNVSN 108 213\nNo maternal vaccine 89 (82) 142 (67) Not Applicable Not Applicable Reference\nMaternal vaccine‡19 (18) 71 (33) 32 (17 -58) 71 (50 -103) 70 (28 -88)§Maternal vaccine effectiveness (VE) against RSV -associated hospitalization  \namong infants in their first RSV season, VISION & NVSN, 2024 –2025\nMaternal RSV vaccine was effective against RSV -associated hospitalization in infants.\n*VISION analysis included children who were born ≥14 days after maternal RSV vaccine dose.\n†Vaccine effectiveness (VE) calculated as (1 -adjusted odds ratio)*100, with adjusted odds ratio estimated using multivariable log istic regression model, adjusting for site, age in months, calendar date, race and ethnicity, and sex.\n‡NVSN analysis included children who born  ≥14 days after maternal RSV vaccine dose\n§Vaccine effectiveness (VE) calculated as (1 -adjusted odds ratio)*100, with adjusted odds ratio estimated using multivariable log istic regression model, adjusting for site, age in months, month of enrollment, race/ethnicity, and health \ninsurance status . 140 20 40 60 80 100\nVaccine Effectivness (%)\n•These surveillance systems have different enrollment methodologies and source populations and may \nnot be directly comparable.\n•Residual confounding was possible\n•Misclassification of RSV immunization status was possible, although all systems used multiple sources to \nverify immunization status\n•VISION:  \n-Cases may have sought care for something other than RSV\n-All RSV testing was clinician -directed\n-EHR data may not fully capture all underlying medical conditions, which may be associated with likelihood of \nimmunization and risk of severe RSV disease\n•NVSN:\n-May not be nationally representative\n-Cases may have sought care for something other than RSV\n•Overcoming Network:\n-Enrollment began after the RSV season started\n-All RSV testing was clinician -directed Limitations of product effectiveness analyses\n15\nConclusions\n16\nSummary of RSV prevention product effectiveness (PE) among infants in \ntheir first RSV season, 2024 –2025\nOutcome Product CDC Network Product Efficacy* /Effectiveness (95% CI)\nRSV-associated ED visitNirsevimabVISION 63 (56 -69)\nNVSN 76 (55 -87)\nClinical Trial Not Applicable\nMaternal VaccineVISION 54 (35 -67)\nClinical Trial Not Applicable\nRSV-associated hospitalizationNirsevimab*VISION 79 (67 -87)\nNVSN 82 (71 -88)\nClinical Trial 81 (62 -90)\nMaternal Vaccine†VISION 79 (55 -90)\nNVSN 70 (28 -88)\nClinical Trial 57 (15 -80)\nRSV-associated Intensive Care \nUnit (ICU) admissionNirsevimab*VISION 82 (57 -93)\nNVSN 88 (63 -96)\nOvercoming 80 (73 -85)\nClinical Trial 90 (16 -99)\n*Jones et al. MMWR  2023. Available:  https://www.cdc.gov/mmwr/volumes/72/wr/mm7234a4.htm\n†Kampmann et al. NEJM 2023. Available: https://www.nejm.org/doi/full/10.1056/NEJMoa2216480 170 20 40 60 80 100\nVaccine Effectivness (%)\n•Nirsevimab was effective against RSV -associated \nemergency department (ED) encounters, \nhospitalization, and critical illness among infants \nin their first RSV season during the 2024 –2025 \nRSV season in the United States.\n•Maternal vaccination was effective against RSV -\nassociated ED encounters and hospitalization \nduring the 2024 –2025 RSV season in the United \nStates.\n•Ongoing monitoring of post -licensure nirsevimab  \nand maternal RSV vaccine effectiveness will be \nnecessary to assess additional outcomes.Product Effectiveness Conclusions\n18\nImpact of RSV prevention products on U.S. \npediatric RSV -associated hospitalizations\nAnalyzed data from two active, population -based U.S. surveillance systems \nthat monitor laboratory -confirmed RSV -associated hospitalizations\nRSV-NET NVSN\nRESP -NET: Respiratory Virus Hospitalization \nSurveillance Network \n•RSV-NET, FluSurv -NET, COVID -NET\n•Patients of any age from >300 hospitals, 161 \ncounties in 13 states\n•https://www.cdc.gov/rsv/php/surveillance/rsv -net.htmlNVSN: New Vaccine Surveillance Network\n•Children <18 years old hospitalized with acute \nrespiratory illness at 7 academic pediatric health \nsystems in 7 states\n•https://www.cdc.gov/nvsn/php/about/index.html\n20\nMethods\n•Ecological analysis that compared RSV -associated hospitalizations and rates between \nRSV seasons before and after RSV prevention product introduction\n‒Pre-pandemic, before product introduction\n▪RSV-NET: 2018 –19, 2019 –20\n▪NVSN: 2017 –19, 2018 –19, 2019 –20\n‒After product introduction\n▪2024 –25, 2nd year of product availability\n•Excluded RSV seasons\n‒2020 –21, 2021 –22, and 2022 –23 seasons impacted by COVID -19 pandemic\n‒2023 –24, 1st year of product availability\n▪Low product availability and uptake21\nMethods\n•Compared adjusted RSV -associated hospitalization and ICU admission rates * \nbefore and after RSV prevention product introduction\n–Weekly  (RSV -NET) and monthly  (NVSN) hospitalization rates during 2024 –25 \nversus same periods in prior seasons\n–Cumulative  2024 –25 hospitalization rates compared to pooled rates from prior \nseasons\n▪Hospitalization rates (RSV -NET and NVSN)\n▪ICU admission rates (RSV -NET)\n–Estimated rate ratios (RR) comparing cumulative rates\n–Estimated relative rate reductions (RRR): (1 -RR) x 100\n*RSV -NET rates adjusted for undertesting and test sensitivity; NVSN rates adjusted for enrollment rates, weeks with <7 surveillance days, test sensitivity, and hospital market share  \n22\n•Assessed changes in rates before and after RSV prevention \nproduct introduction for three age groups with different RSV \nprevention optionsMethods\n23\n•Assessed changes in rates before and after RSV prevention \nproduct introduction for three age groups with different RSV \nprevention options\n‒Infants aged 0 –7 months\n▪Eligible for nirsevimab\n▪Potentially protected by maternal RSV vaccinationMethods\n24\n\n•Assessed changes in rates before and after RSV prevention \nproduct introduction for three age groups with different RSV \nprevention options\n‒Infants aged 0 –7 months\n▪Eligible for nirsevimab\n▪Potentially protected by maternal RSV vaccine\n‒Children aged 8 –19 months\n▪Small number may have been eligible for\nnirsevimab based on risk conditionsMethods\n25\n•Assessed changes in rates before and after RSV prevention \nproduct introduction for three age groups with different RSV \nprevention options\n‒Infants aged 0 –7 months\n▪Eligible for nirsevimab\n▪Potentially protected by maternal RSV vaccine\n‒Children aged 8 –19 months\n▪Small number may have been eligible for\nnirsevimab based on risk conditions\n‒Children aged 20 –59 months\n▪Age group ineligible for RSV prevention productsMethods\n26\n•Assessed changes in rates before and after RSV prevention \nproduct introduction for three age groups with different RSV \nprevention options\n‒Infants aged 0 –7 months\n▪Eligible for nirsevimab\n▪Potentially protected by maternal RSV vaccine\n‒Children aged 8 –19 months\n▪Small number may have been eligible for\nnirsevimab based on risk conditions\n‒Children aged 20 –59 months\n▪Age group ineligible for RSV prevention productsMethods\nComparison populations \nmostly ineligible for RSV \nprevention products.\nIncluded  to detect \nhospitalization rate \nchanges unrelated to \nRSV product uptake.\n27\nhttps://www.cdc.gov/rsvvaxview/dashboard/nirsevimab -coverage -infants.htmlDuring 2024 –25, RSV prevention products were available before RSV season \nonset in most states,  with product coverage that increased over time. \n•21% to 48% coverage among infants aged \n0–7 months across 36 reporting \njurisdictions as of March 2025\n•39% of eligible* pregnant women aged \n18–49 years received RSV vaccine as of \nJanuary 2025Nirsevimab Maternal RSV Vaccine\n*includes pregnant women who reached at least 32 weeks’ gestation as of September 1, 2024\nhttps://www.cdc.gov/rsvvaxview/dashboard/pregnant -women -coverage.htmlIIS Nirsevimab Coverage (%) \nfor 2024–25 Season\n28\n2018–19\nRate2019–20\nRate2024–25\nRateInfants\nvs vs2018–19\nRate2019–20\nRate2024–25\nRatevs vs2018–19\nRate2019–20\nRate2024–25\nRatevs vsToddlers ChildrenFor an ecological analysis, RSV -associated hospitalization rates can be assessed in three age \ngroups across different RSV seasons\n29\n\nIn the absence of new RSV prevention products, RSV -associated hospitalization rates would be \nexpected to vary by age group, but remain consistent within each age group across seasons.\n2018–19\nRate2019–20\nRate2024–25\nRateInfants\nvs vs2018–19\nRate2019–20\nRate2024–25\nRatevs vs2018–19\nRate2019–20\nRate2024–25\nRatevs vsToddlers Children\n30\n\nBecause new RSV prevention products are only recommended for some children, RSV -associated hospitalization rates \nfrom seasons before product introduction can be compared to 2024 –25 (after product introduction), by age group\n2018–19\nRate2019–20\nRate2024–25\nRatevs vs2018–19\nRate2019–20\nRate2024–25\nRatevs vs2018–19\nRate2019–20\nRate2024–25\nRatevs vsInfants aged 0 –7 months, eligible \nfor nirsevimab or potentially \nprotected by maternal RSV vaccineChildren aged 8 –19 months, some of \nwhom may have been eligible for nirsevimab \nbased on risk conditionsChildren aged 20 –59 months, age \ngroup ineligible for RSV prevention \nproducts\n31\n\nThe analysis can assess whether RSV -associated hospitalization rates in 2024 –25 compared to prior \nseasons changed more for infants aged 0 –7 months than for children aged 8 –19 and 20 –59 months\n2018–19\nRate2019–20\nRate2024–25\nRatevs vs2018–19\nRate2019–20\nRate2024–25\nRatevs vs2018–19\nRate2019–20\nRate2024–25\nRatevs vsInfants aged 0 –7 months, eligible \nfor nirsevimab or potentially \nprotected by maternal RSV vaccineChildren aged 8 –19 months, some of \nwhom may have been eligible for nirsevimab \nbased on risk conditionsChildren aged 20 –59 months, age \ngroup ineligible for RSV prevention \nproducts\n32\n\nResults\nCombined, RSV -NET and NVSN identified >20,000 children \naged <5 years with RSV -associated hospitalizations\nRSV-NET NVSN\n2018–20 2024–25 2017–20 2024–25 Total*\nHospitalizations 9,717 7,003 3,119 1,001 20,840\nIntensive Care Unit (ICU) \nAdmissions2,332 251 671 200 3,454\n34*Children at two surveillance sites for NVSN and RSV -NET could be documented in both systems. In 2018 –20, 252 hospitalized child ren were enrolled in both systems, with 54 also having an ICU \nadmission. During 2024 –25, 76 children were enrolled in both systems with 25 having an ICU admission. \nProportions of children aged <5 years with an RSV -associated \nhospitalization who were aged  0–7 months decreased, and median age \nincreased, in 2024 –25 compared to seasons before product introduction\n28\n1431\n1523\n1525\n22\n0102030405060708090100\n2018–20 2024–25 2017–20 2024–25Proportion of all children aged <5 years with RSV -associated \nhospitalizationChildren aged 20 –59 months\nChildren aged 8 –19 months\nInfants aged 3 –7 months\nInfants aged 0 –2 months\nMedian age in months 7.7 15.4 6.3 12.7RSV-NET NVSN\n29%38%51%46%\n35\nCumulative adjusted RSV -associated hospitalization rates in 2024 –25 \nwere compared to seasons before product introduction by age group\n17.016.0\n5.85.3\n1.71.1\n02468101214161820\nRSV-NET NVSN RSV-NET NVSN RSV-NET NVSN\n0–7 months 8–19 months 20–59 monthsHospitalization rate per 1,000 children2018-20\n(RSV-NET) or\n2017-20\n(NVSN)\nPatton & Moline et al, MMWR 2025; Curns  et al. Pediatrics 202436Bar labels indicate cumulative laboratory -confirmed RSV -associated hospitalizations per 1,000 children as of April 30 (RSV -NET) or March 31 (NVSN) ea ch season. Rates use U.S. population denominators. RSV -NET rates are adjusted to account for RSV underdetection because of \ntesting practices and test sensitivity. NVSN rates are adjusted to account for weeks with <7 days of surveillance, the proportion of eligible children not enrolled, sensitivity of respiratory syncytial virus reverse -transcription polymerase chain reaction testing compared to serology, \nand each site’s estimated market share of acute respiratory illness hospitalizations by age. Error bars denote 95% confidence  intervals (95% CI).\nCumulative adjusted RSV -associated hospitalization rates in 2024 –25 \nwere compared to seasons before product introduction by age group\n17.016.0\n5.85.3\n1.71.110.511.0\n8.1\n6.3\n2.9\n1.9\n02468101214161820\nRSV-NET NVSN RSV-NET NVSN RSV-NET NVSN\n0–7 months 8–19 months 20–59 monthsHospitalization rate per 1,000 children2018-20\n(RSV-NET) or\n2017-20\n(NVSN)\n2024-25\n37\nPatton & Moline et al, MMWR 2025; Curns  et al. Pediatrics 2024Bar labels indicate cumulative laboratory -confirmed RSV -associated hospitalizations per 1,000 children as of April 30 (RSV -NET) or March 31 (NVSN) ea ch season. Rates use U.S. population denominators. RSV -NET rates are adjusted to account for RSV underdetection because of \ntesting practices and test sensitivity. NVSN rates are adjusted to account for weeks with <7 days of surveillance, the proportion of eligible children not enrolled, sensitivity of respiratory syncytial virus reverse -transcription polymerase chain reaction testing compared to serology, \nand each site’s estimated market share of acute respiratory illness hospitalizations by age. Error bars denote 95% confidence  intervals (95% CI).\nRRR=relative rate reduction, 95%CI = 95% confidence interval\nBar labels indicate cumulative laboratory -confirmed RSV -associated hospitalizations per 1,000 children as of April 30 (RSV -NET) or March 31 (NVSN) each season. Rates use U.S. population denominators. RSV -NET rates are adjusted to account for RSV underdetection  because of \ntesting practices and test sensitivity. NVSN rates are adjusted to account for weeks with <7 days of surveillance, the proportion of eligible children not enrolled, sensitivity of respiratory syncytial virus reverse -transcription polymerase chain reaction testing compared to serology, \nand each site’s estimated market share of acute respiratory illness hospitalizations by age. Error bars denote 95% confidence  intervals.Among infants aged 0–7 months  (eligible for p rotection by nirsevimab or \nmaternal vaccine ) RSV -associated hospitalization rates were reduced by 38% and \n31%  in 2024–25 compared to seasons before product introduction \n17.016.0\n5.85.3\n1.71.110.511.0\n8.1\n6.3\n2.9\n1.9\n02468101214161820\nRSV-NET NVSN RSV-NET NVSN RSV-NET NVSN\n0–7 months 8–19 months 20–59 monthsHospitalization rate per 1,000 children2018-20\n(RSV-NET) or\n2017-20\n(NVSN)\n2024-25RRR=31%\n(95% CI 22 -44)RRR=38%\n(95% CI 35 -41)\nNo reductions\n38\nPatton & Moline et al, MMWR 2025; Curns  et al. Pediatrics 2024\nBar labels indicate cumulative laboratory -confirmed RSV -associated hospitalizations per 1,000 children as of April 30 (RSV -NET) or March 31 (NVSN) each season. Rates use U.S. population denominators. RSV -NET rates are adjusted to account for RSV \nunderdetection  because of testing practices and test sensitivity. NVSN rates are adjusted to account for weeks with <7 days of surveillance, the proportion of eligible children not enrolled, sensitivity of respiratory syncytial virus reverse -transcription polymerase \nchain reaction testing compared to serology, and each site’s estimated market share of acute respiratory illness hospitalizat ions by age. Error bars denote 95% confidence intervals.Cumulative adjusted RSV -associated hospitalization rates in 2024 –25 \nwere compared to prior seasons among subgroups of infants aged 0 –2 \nand 3–7 months\n24.923.4\n12.211.5\n051015202530\nRSV-NET NVSN RSV-NET NVSN\n0–2 months 3–7 monthsHospitalization rate per 1,000 children2018-20\n(RSV-NET) or\n2017-20\n(NVSN)\nPatton & Moline et al, MMWR 2025; Curns  et al. Pediatrics 202439\nRRR=relative rate reduction, 95%CI = 95% confidence interval\nBar labels indicate cumulative laboratory -confirmed RSV -associated hospitalizations per 1,000 children as of April 30 (RSV -NET) or March 31 (NVSN) each season. Rates use U.S. population denominators. RSV -NET rates are adjusted to account for RSV \nunderdetection  because of testing practices and test sensitivity. NVSN rates are adjusted to account for weeks with <7 days of surveillance, the proportion of eligible children not enrolled, sensitivity of respiratory syncytial virus reverse -transcription polymerase \nchain reaction testing compared to serology, and each site’s estimated market share of acute respiratory illness hospitalizat ions by age. Error bars denote 95% confidence intervals.RSV-associated hospitalization rates were reduced by 47% in RSV -NET \nand 46% in NVSN among infants aged 0 –2 months in 2024 –25 \ncompared to seasons before product introduction \n24.923.4\n12.211.513.212.6\n8.910.1\n051015202530\nRSV-NET NVSN RSV-NET NVSN\n0–2 months 3–7 monthsHospitalization rate per 1,000 children2018-20\n(RSV-NET) or\n2017-20\n(NVSN)\n2024-25RRR= 47% (95% CI 43 -50) RRR= 46% (95% CI 35 -57)\nRRR= 27% (95% CI 22 -32)RRR=20% (95% CI -4-37)\nPatton & Moline et al, MMWR 2025; Curns  et al. Pediatrics 202440\nConclusions\nRSV Prevention Product Impact Conclusions\n•Two U.S. population -based surveillance \nnetworks demonstrated reductions in RSV -\nassociated hospitalization rates during 2024 –25 \namong infants eligible for RSV prevention \nproduct protection\n-38% (RSV -NET) and 31% (NVSN) reductions in \n2024 –25 compared to RSV seasons before product \nintroduction among infants aged 0 –7 months\n42\n\nConclusions\n•Reductions in RSV -associated hospitalization were \ngreatest among infants aged 0 –2 months born just \nbefore or during the RSV season\n-47% (RSV -NET) and 46% (NVSN) reductions in 2024 –25\n-Group at highest risk of hospitalization\n-Underscores importance of protection through maternal \nvaccination during pregnancy or nirsevimab in first week \nof life\n•Ongoing monitoring of RSV disease trends —including \nseverity and age distribution —is critical to assess \nsustained impact of RSV prevention products\n43\nAcknowledgements\n▪CDC National Center for Immunizations and Respiratory \nDiseases (NCIRD)\n▪CDC -funded partners\n•VISION\n•New Vaccine Surveillance Network (NVSN)\n•Overcoming Network\n•RSV-NET\n44\nwww.cdc.govFor more information, contact CDC\n1-800 -CDC -INFO (232 -4636)\nTTY:  1 -888 -232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention.\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\n\nBar labels indicate the incidence rate per 1,000 children.  Rates were calculated using county -specific denominators from the 20 20 US bridged -race population estimates, and population -based numerators based on the observed number of hospitalizations at eac h site adjusted to \naccount for weeks with <7 days of surveillance, the proportion of eligible children not enrolled, sensitivity of respiratory syncytial virus reverse -transcription polymerase chain reaction testing compared to serology, and each site’s estimated market shar e of ARI hospitalizations by age. \nError bars denote 95% confidence intervals determined based on 1000 bootstrap samples for each rate.RSV-associated hospitalization rates among children <5 years of \nage, by season, New Vaccine Surveillance Network, 2017 -2025\nCurns et al. Pediatrics 2024; Patton & Moline et al, MMWR 2025.\n25.67\n13.35\n8.41\n4.07\n1.104.1919.1\n12.0\n5.3\n2.9\n0.73.027.0\n15.7\n8.0\n4.4\n1.24.423.9\n13.7\n7.2\n3.8\n1.03.926.6\n16.2\n8.7\n5.2\n1.65.012.0\n10.7\n6.3\n5.8\n1.43.7\n05101520253035\n0-2 Months 3-5 months 6-11 months 12-23 months 24-59 months 0-59 monthsHospitalization rate per 1,000 children\nAge Group2017-2018\n2018-2019\n2019-2020\n2017-2020 Average\n2023-2024\n2024-2025\n46\nBar labels indicate the incidence rate per 1,000 children.  Rates were calculated using county -specific denominators from the 20 20 US bridged -race population estimates, and population -based numerators based on the observed number of hospitalizations at eac h site adjusted to \naccount for weeks with <7 days of surveillance, the proportion of eligible children not enrolled, sensitivity of respiratory syncytial virus reverse -transcription polymerase chain reaction testing compared to serology, and each site’s estimated market shar e of ARI hospitalizations by age. \nError bars denote 95% confidence intervals determined based on 1000 bootstrap samples for each rate.RSV-associated hospitalization rates among children <5 years of \nage, by season, RSV -NET, 2018 –2025\nRSV-NET unpublished data\n22.1\n14.8\n8.9\n6.5\n5.0\n1.726.8\n15.6\n10.3\n7.9\n5.2\n1.9\n0.41 0.32 0.14 0.16 0.09 0.0427.0\n13.7\n9.1\n6.6\n5.2\n1.935.7\n24.6\n18.4\n12.3\n10.0\n4.222.9\n16.8\n13.6\n10.4\n7.3\n2.613.2\n9.8\n8.5 8.77.8\n2.9\n0510152025303540\n0-2 months 3-5 months 6-7 months 8-11 months 12-19 months 20-59 monthsHospitalization rate per 1,000 children2018-19 2019-20 2020-21 2021-22 2022-23 2023-24 2024-25\n47\nRSV-NET NVSNWeekly (RSV -NET) and monthly* (NVSN) adjusted RSV -associated hospitalization rates in 2024 –25 were lower  compared to \nprior seasons among infants aged 0–7 months  and\nwere the same or higher  than prior seasons among children aged 20–59 months\n00.20.40.60.811.21.41.61.8\n40 42 44 46 48 50 52 2 4 6 8 10 12 14 16 18Adjusted RSV hospitalization rate per 1,000 population\nSurveillance week2024-25 Pooled 2018 –2020\nMinimum 2018 –2020 Maximum 2018 –2020\n00.20.40.60.811.21.41.61.8\n40 42 44 46 48 50 52 2 4 6 8 10 12 14 16 18Adjusted RSV hospitalization rate per 1,000 population\nSurveillance week2024-25 Pooled 2018 –2020\nMinimum 2018 –2020 Maximum 2018 –2020\n00.20.40.60.811.21.41.61.8\n40 42 44 46 48 50 52 2 4 6 8 10 12 14 16 18Adjusted RSV hospitalization rate per 1,000 population\nSurveillance week2024-25 Pooled 2018 –2020\nMinimum 2018 –2020 Maximum 2018 –2020Infants aged 0 –7 months\nEligible for protection by nirsevimab or \nmaternal vaccineChildren aged 8 –19 months\nSmall number eligible for nirsevimabChildren aged 20 –59 months \nIneligible for either product\n0123456\nOctober† November December January February March† April†Monthly RSV -associated hospitalization rate per 1,000 population\nMonth of RSV Season2024 –25 Pooled 2017 –2020\nMinimum 2017 –2020 Maximum 2017 –2020\n0123456\nOctober November December January February March† AprilMonthly RSV -associated hospitalization rate per 1,000 population\nMonth of RSV Season2024 –25 Pooled 2017 –2020\nMinimum 2017 –2020 Maximum 2017 –2020\n0123456\nOctober November December January February March† April†Monthly RSV -associated hospitalization rate per 1,000 population\nMonth of RSV Season2024 –25 Pooled 2017 –2020\nMinimum 2017 –2020 Maximum 2017 –2020\n48\nPatton & Moline et al, MMWR 2025*2024 -25 NVSN rates through March 31, 2025. †NVSN rates should be interpreted with caution as relative standard error ≥30 or n <5: 0 –7 months March 2024 -25, 8 –19 months Mar ch 2017 –20 max, 20 –59 months October, March and April 2017 –20 min and April 2017 –20 pooled\nRSV-NET rates are adjusted to account for RSV underdetection  because of testing practices and test sensitivity. NVSN rates are adjusted to account for weeks with <7 days of surveillance, the proportion of eligible children not enrolled, sensitivity of respiratory syncytial virus reverse -transcription polymerase chain reaction \ntesting compared to serology, and each site’s estimated market share of acute respiratory illness hospitalizations by age.  \nRRR=relative rate reduction, 95%CI = 95% confidence interval\nBar labels indicate cumulative laboratory -confirmed RSV -associated hospitalizations per 1,000 children as of April 30 (RSV -NET) or March 31 (NVSN) each season. Rates use U.S. population denominators. RSV -NET rates are adjusted to account for RSV \nunderdetection  because of testing practices and test sensitivity. NVSN rates are adjusted to account for weeks with <7 days of surveillance, the proportion of eligible children not enrolled, sensitivity of respiratory syncytial virus reverse -transcription polymerase \nchain reaction testing compared to serology, and each site’s estimated market share of acute respiratory illness hospitalizat ions by age. Error bars denote 95% confidence intervals.RSV-associated ICU admission rates in RSV -NET were reduced by 38%  \namong infants aged 0–7 months ; no reductions occurred among \nchildren aged 8 –19 and 20 –59 months\n5.2\n1.4\n0.43.2\n1.3\n0.4\n0123456\n0–7 months 8–19 months 20–59 monthsICU admission rate per 1,000 children2018-20\n2024-25RRR= 38% (95% CI 32 -43)\nNo reductions\nRSV-NET unpublished data49\n8.2\n3.44.8\n2.3\n012345678910\n0–2 months 3–7 monthsICU admission rate per 1,000 children2018-20\n2024-25RRR= 42% (95% CI 34 -48)RSV-associated ICU admission rates in RSV -NET were reduced by 42% \namong infants aged 0 –2 months and by 31% among infants aged 3 –7 \nmonths\nRRR=31% (95% CI 21 -40)\n50\nRSV-NET unpublished dataRRR=relative rate reduction, 95%CI = 95% confidence interval\nBar labels indicate cumulative laboratory -confirmed RSV -associated hospitalizations per 1,000 children as of April 30 (RSV -NET) or March 31 (NVSN) ea ch season. Rates use U.S. population denominators. RSV -NET rates are adjusted to account for RSV \nunderdetection  because of testing practices and test sensitivity. NVSN rates are adjusted to account for weeks with <7 days of surveillance, the proportion of eligible children not enrolled, sensitivity of respiratory syncytial virus reverse -transcription polymerase \nchain reaction testing compared to serology, and each site’s estimated market share of acute respiratory illness hospitalizat ions by age. Error bars denote 95% confidence intervals.\nMeta -analysis of nirsevimab  effectiveness against \nRSV-associated hospitalization, 2023 -2024 season\nPE (95% CI)\n79 (72 -85)\n77 (65 -86)\n76 (65 -83)\n85 (72 -92)\n66 (62 -70)\n99 (76 -100)\n71 (39 -86)\n90 (86 -93)\n81 (63 -90)\n85 (23 -97)\n90 (84 -93)\n71 (58 -81)\n80 (76 -83)\n93 (84 -97)\n95 (89 -98)\n86 (66 -95)\n83 (77 -88)\nSumsuzzman  DM et al. Real -world effectiveness of nirsevimab  against respiratory syncytial virus disease in infants: a systematic review and meta -analysis. Lancet Child Adolesc  Health  2025\nPE: Product Effectiveness; CI: Confidence IntervalVISION 79 (67 -87)\nNVSN 82 (71 -88)\n51\nMeta -analysis of nirsevimab  effectiveness against \nRSV-associated ICU admission, 2023 -2024 season\nSumsuzzman  DM et al. Real -world effectiveness of nirsevimab  against respiratory syncytial virus disease in infants: a systematic review and meta -analysis. Lancet Child Adolesc  Health  2025\nPE: Product Effectiveness; CI: Confidence Interval\nPE (95% CI)\n84 (49 -95)\n52 (-17-87)\n75 (51 -87)\n66 (42 -80)\n74 (56 -85)\n93 (84 -97)\n86 (72 -93)\n84 (69 -92)\n92 (78 -97)\n81 (71 -88)\nVISION 82 (57 -93)\nNVSN 88 (63 -96)\nOC 79 (62 -89)\n52\n•Argentina\n-Razzini  et al.1:  VE against RSV-associated hospitalization  was 81% (95% CI 63 –91) among infants \nunder age 3 months\n-Perez Marc et al.2:  VE against RSV-associated hospitalization was 79% (95% CI 62 –88) among \ninfants under age 3 months\n-Gentile et al.3:  VE against RSV-associated hospitalization was 79% (95% CI: 51 –91) among infants\nunder age 6 months\n•UK\n-Williams et al.4:  VE against RSV-associated hospitalization was 72% (95% CI: 48 –85) among infants\nunder age 3 monthsMaternal RSV vaccine effectiveness estimates from \nArgentina and UK\n1Razzini JL et al. Impact and Effectiveness of Universal Respiratory Syncytial Virus Vaccination During Pregnancy on Infant Ho spitalizations in Buenos Aires: A Retrospective Cohort Study.   VeriXiv .  2025\n2Pérez Marc G et al. Real -world effectiveness of RSVpreF  vaccination during pregnancy against RSV -associated lower respiratory tract disease leading to hospitalisation  in infants during the 2024 RSV season in \nArgentina (BERNI study): a multicentre , retrospective, test -negative, case –control study.  The Lancet Infectious Diseases.   2025\n3Gentile A et al. Maternal Immunization With RSVpreF  Vaccine: Effectiveness in Preventing Respiratory Syncytial Virus –associated Hospitalizations in Infants Under 6 Months in Argen tina: Multicenter Case –control \nStudy. The Pediatric Infectious Disease Journal .  2025\n4Williams TC et al. Bivalent Prefusion F Vaccination in Pregnancy and Respiratory Syncytial Virus Hospitalisation  in Infants: Results of a Prospective, Multi -Centre, Test -Negative Study. Available at SSRN: \nhttps://ssrn.com/abstract=5184994 or http://dx.doi.org/10.2139/ssrn.5184994  53\n•Models did not adjust for healthcare utilization behavior or specific\nunderlying characteristics between vaccinated and unvaccinated patientsProduct Effectiveness Analyses – Controlling for \nConfounding\n54VISION NVSN Overcoming\nAnalysis Multivariable logistic regression \nmodels, adjusting for site, age in \nmonths, calendar date, race and \nethnicity, and sex. \nModels adjusting for underlying \nmedical conditions did not \nmeaningfully change estimates.Multivariable logistic regression \nmodels, adjusting for site, age in \nmonths, and month of enrollment. \nNirsevimab analysis adjusted for \npresence of ≥1 high -risk medical \ncondition for severe RSV \ndisease; maternal RSV analysis \nadjusted for race/ethnicity and \ninsurance status.Multivariable logistic \nregression models, adjusting \nfor site, age in months, \ntiming of enrollment, \npresence of ≥1 underlying \nmedical condition, and social \nvulnerability index.", "summary": "Effectiveness and impact of RSV  prevention products in infants during  the 2024 –2025 RSV season Coronavirus and Other Respiratory Viruses Division June 25, 2025National Center for Immunization and Respiratory Diseases  Product Effectiveness (PE) •Summary of CDC systems used toevaluate PE •Effectiveness of nirsevimab and maternal RSV  vaccine during the 2024 –2025 RSV season in  the U.S. RSV Hospitalization Rates and Product Impact  •Summary of CDC systems used for monitoring  RSV…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-25-26-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-06-25-26/03-MacNeil-Mat-Peds-RSV-508.pdf", "doc_date": "2025-06-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 54}
{"title": "04a DeSilva Mat Peds RSV 508", "content": "Prenatal RSVpreF  Vaccine Safety \n2023 –2024 Respiratory Season\nThe Vaccine Safety Datalink (VSD)\nMalini DeSilva, MD, MPH\nPresentation to ACIP\nJune 25, 2025\n© HealthPartners 2Vaccine Safety Datalink (VSD)\n•Collaborative project between \nCDC and 13 integrated \nhealthcare organizations\n•Monitors safety of vaccines used \nin the U.S., primarily through \nobservational multisite studies\n•Includes data on ~15.5 million \nindividuals across all sites \nannually (~4.5% of U.S. \npopulation)\n•Annual birth cohort ~ 115,000\n•Data is organized using a \ncommon data dictionary with \nstandardized coding systems\n\n© HealthPartners 3Prenatal RSVpreF  vaccine 2023 –2024 season\n•ACIP recommendation 9/22/23:\n•32–36 weeks gestation with\nseasonal administration\n•RSVpreF  clinical trial1\nidentified non -significant\nimbalances among vaccinated\ncompared to placebo in:\n•Preterm births\n•Gestational hypertension and\npreeclampsia\nPhotomicrograph of RSV using indi rect immunofluorescent \nantibody under fluorescent lighting. \nhttps://wwwn.cdc.gov/phil/Details.aspx?pid=6484\n1Simoes EAF, Center KJ, Tita ATN, et al. Prefusion F Protein -Based Respiratory Syncytial Virus Immunization in Pregnancy. N Engl J Med . Apr \n28 2022;386(17):1615 -1626. doi:10.1056/NEJMoa2106062\n© HealthPartners 4❖Acute outcomes within 42 days of vaccination\n❖Preterm birth (birth <37 weeks gestational age)\n❖Small for Gestational Age (SGA) at birth\n❖Stillbirth (antepartum)\n❖Hypertensive disorders of Pregnancy (HDP):\n•Gestational hypertension (GHTN) - New onset HTN after 20 weeks \ngestation\n•Preeclampsia - New onset or worsening chronic HTN after 20 weeks \ngestation with or without severe features \n•Eclampsia - Convulsive manifestation of HDP with no other etiology\n•HELLP Syndrome (hemolysis, elevated liver enzymes, and low \nplatelets)Prenatal RSVpreF  vaccine safety outcomes\n© HealthPartners 5Methods - Target trial emulation design \nProtocol \nComponent\nEligibility criteria Pregnant women 16 –49 years with gestational age 32 –<37 weeks \nduring 9/22/2023 – 1/31/24 or 2/29/24 for two sites\nTreatment \nstrategies•RSVpreF  vaccination (exposed)\n•No RSVpreF  vaccination (unexposed)\nAssignment \nproceduresExposed women matched 1:1 to unexposed on: \n•VSD site \n•Propensity to be vaccinated*\n•Gestational week\nFollow -up period •Index date (vaccination or gestational day of vaccine for \nunexposed match) through 2 weeks after pregnancy end\n•Follow up censored at crossover to RSVpreF  vaccinationRecreating a randomized experiment from observational data\n*Covariates included: Maternal age, calendar week at pregnancy start, # of weeks with prenatal care, \nrace/ethnicity, comorbidities (i.e., HTN, DM, GHTN, GDM, obesity, substance use), history of preterm labor, \npoor fetal growth, supervision of high -risk pregnancy, enrollment, and gestational week\n© HealthPartners 6Analysis\n•Estimated risk ratios with 95% Confidence Interval (CI) using Log \nbinomial model with robust variance with adjustment for nulliparity\n•For small for gestational age at birth, matched set excluded if infant \nweight not available for either infant in matched pair\n•For hypertensive disorders of pregnancy, matched set excluded if onset \noccurs before or on index date for either woman\n© HealthPartners 7Balance plot before and after matching\n•SMD =  standardized mean differences for \nvariables included in the propensity score \nbefore and after matching.\n•Common way to assess covariate balance \nafter matching\n•Interpretation: -0.2 to 0.2 = small difference \nbetween groups\nNotes:\n•*Race/Ethnicity\n•LMP = last menstrual period\n•Enrollment = continuous health plan enrollment from 90 \nprior to LMP through index week\n•ICD-10 codes for:\n•High Risk = O09.* (Supervision of care for a high -\nrisk pregnancy)\n•Poor fetal growth = O36.5\n•Preterm labor history = O09.21, Z87.51\n \n\n© HealthPartners 8Matched cohort* characteristics, N = 13,966\nRSVpreF  Vaccinated, n (%) Unvaccinated match, n (%)\nAge group\n•16–24 years 1405 (10.1) 1595 (11.4)\n•25–29 years 3151 (22.6) 3439 (24.6)\n•30–34 years 5461 (39.1) 5272 (37.7)\n•35–39 years 3286 (23.5) 3020 (21.6)\n•40–49 years 663 (4.7) 640 (4.6)\nRace/Ethnicity\n•Asian 3039 (21.8) 2635 (18.9)\n•Black 862 (6.2) 991 (7.1)\n•Hispanic 4459 (31.9) 4691 (33.6)\n•White 4542 (32.5) 4541 (32.5)\n•Other/Unknown 1064 (7.6) 1108 (7.9)\n≥1 other vaccine during \npregnancy13758 (98.5) 11315 (81.0)\nNulliparity 5914 (46.4) 4853 (38.7)\n*Not unique individuals due to crossover from unvaccinated to vaccinated\n© HealthPartners 91–6 and 1 –21 day acute safety outcome risks among pregnant women \nreceiving RSVpreF vaccine and unvaccinated matches \n\n© HealthPartners 101–42 day acute safety outcome risk among pregnant women \nreceiving RSVpreF vaccine and unvaccinated matches\n\n© HealthPartners 11Preterm birtha risk among pregnant women receiving RSVpreF  \nvaccine and unvaccinated matches\nMatched \npairs, NRSVpreF vaccinated Unvaccinated matchAdjusted Risk \nRatio (95% CI)b\nN events* Preterm birth % N events* Preterm birth %\n13,966 563 4.0 627 4.5 0.90 (0.80 –1.00)\naPreterm  birth = birth <37 weeks gestational age\nbAdjusted  for nulliparity\n*Events only included through date of censoring when unvaccinated pair crosses over to vaccinated\n© HealthPartners 12SGAa at birth risk in infants born to RSVpreF  vaccinated \npregnant person or unvaccinated pregnant matches\nMatched \npairs, NRSVpreF vaccinated Unvaccinated matchAdjusted Risk \nRatio (95% CI)b\nN events* SGA at birth % N events* SGA at birth %\n11,822 799 6.8 774 6.5 0.99 (0.90 –1.09)\naSGA  at birth = Small for gestational age at birth; birth weight <10th percentile for gestational age \ncompared with a U.S. reference population1\nbAdjusted  for nulliparity\n*Events only included through date of censoring when unvaccinated pair crosses over to vaccinated \n Note: 11,822 matched pairs with complete infant weight data (85%)\nTalge NM, Mudd LM, Sikorskii  A, Basso O. United States birth weight reference corrected for implausible gestational age estimates. Pediatrics . May \n2014;133(5):844 -53. doi:10.1542/peds.2013 -3285\n© HealthPartners 13Stillbirth risk in RSVpreF  vaccinated pregnant women or \nunvaccinated pregnant matches\nMatched \npairs, NRSVpreF  vaccinated Unvaccinated matchAdjusted Risk \nRatio (95% CI)a\nN events*Stillbirths per \n1000N events*Stillbirths per \n1000 \n13,966 11 0.79 10 0.72 1.09 (0.46 –2.58)\naAdjusted  for nulliparity\n*Events only included through date of censoring when unvaccinated pair crosses over to vaccinated\n© HealthPartners 14Hypertensive disorders of pregnancy (HDP) risk among pregnant women \nreceiving RSVpreF vaccine and unvaccinated matches, N = 13,474\nOutcome RSVpreF  vaccinated Unvaccinated matchAdjusted Risk \nRatio (95% CI)a\nN events* % N events* %\nAny HDP 2344 17.4 2056 15.3 1.09 (1.03 –1.15)\nEclampsia OR\nHELLP40 0.3 50 0.4 0.77 (0.51 –1.16)\nPreeclampsia 1198 8.9 1021 7.6 1.12 (1.03 –1.21)\nGestational \nhypertensionb1069 8.8 939 7.8 1.10 (1.01 -1.19)\naAdjusted  for nulliparity\nbMatched  pairs = 12104; excludes matched pairs with chronic hypertension\n*Events only included through date of censoring when unvaccinated pair crosses over to vaccinated\n© HealthPartners 15Evaluation of rates of cesarean delivery, admissions following birth \nhospitalization, and lengths of stay for patients with hypertensive \ndisorders of pregnancy (HDP) by RSVpreF vaccination status\nHDP Severity indicatorRSVpreF  \nvaccinated\nN = 2344Unvaccinated \nmatch \nN = 2056\nN (%) N (%)\nCesarean delivery 795 (33.9) 675 (32.8)\nHDP admission ≤ 14 days following birth \nhospitalization184 (7.8) 165 (8.1)\nLength of stay >3 days for birth hospitalization\nInfantaCesarean delivery 125 (17.8) 123 (21.4)\nNSVD 93 (6.8) 70 (5.9)\nMotherCesarean delivery 384 (49.0) 310 (46.0)\nNSVD 277 (18.3) 245 (17.9)\nNSVD = normal spontaneous vaginal delivery\naMissing : RSVpreF  vaccinated = 282 ; Unvaccinated = 300\n© HealthPartners 16\n\n© HealthPartners 17\n•Retrospective observational cohort study of patients who delivered at 32 0/7 \nweeks’ gestation or later at 2 NYC hospitals 9/22/23 – 1/31/24\n•Stratified analyses by site and insurance status, association remained among \nthose with private insurance and at 1 of 2 sites\n\n© HealthPartners 18❖RSVpreF  vaccine not associated with increased risk for \n•Acute safety outcomes\n•Preterm birth\n•SGA at birth\n•Stillbirth\n❖RSVpreF vaccine associated with small but statistically \nincreased risk for HDP\n•Potential residual confounding or outcome misclassification\n•Severity of HDP similar between vaccinated and unvaccinated women based on \nrates of c -section, admission following birth hospitalization, and length of stay\n❖2024 –2025 season analysis pendingConclusions from 2023 –2024 respiratory season findings\n© HealthPartners 19HealthPartners\n❖Malini DeSilva\n❖Elyse Kharbanda\n❖Jacob Haapala\n❖Gabriela Vazquez -Benitez\n❖Leslie Kuckler\n❖Jingyi Zhu\n❖Sunita Thapa\n❖Nicole Trower\n❖VSD site PIsOur Team\nWeill Cornell Medicine\n•Heather Lipkind\nKaiser  Northwest\n•Kimberly Vesco\nCDC\n•Eric Weintraub\n•Elizabeth Quincer\n© HealthPartners 20•Onset = 1st HDP diagnosis at or after 20+0 weeks GA\n•Evaluate as combined outcome (any HDP) and individual outcomes\n•For individual outcomes, only include most severe outcome:\nHypertensive disorders of pregnancy diagnoses\nPatient GHTN Pre-eclampsia Eclampsia OR HELLP\n1 X\n2 X X\n3 X X X\nCount 0 2 1GHTN → preeclampsia → Eclampsia = HELLP\nGHTN = gestational hypertension; HELLP = hemolysis, elevated liver enzymes, and low \nplatelet syndrome; GA = gestational ageHypertensive Disorders of Pregnancy (HDP)\n© HealthPartners 21Acute outcomes\nOutcome Risk window(s) \n(days)Background \nrate/10,000*RSVpreF  clinical trial, \nN=3682, n (%)**\nAnaphylaxis 0–1 n/a n/a\nFever 1–7 3.3 3%\nMalaise / fatigue 1–7 11.4 46%\nSkin and soft tissue or local allergic reactions 1–7 7.0 41%\nAcute disseminated encephalomyelitis 1–21, 1 –42 0 n/a\nAcute myocardial infarction 1–21, 1 –42 0.3 n/a\nAppendicitis 1–21, 1–42 0.6 n/a\nBell's Palsy 1–21, 1–42 0.8 n/a\nDisseminated intravascular coagulation (DIC) 1–21, 1–42 0.3 n/a\nGuillain -Barré syndrome 1–21, 1–42 0 n/a\nImmune thrombocytopenic purpura (ITP) 1–21, 1–42 7.6 n/a\nLymphadenopathy / lymphadenitis 1–21, 1–42 4.6 <0.1%\n*Identified from unvaccinated pregnant persons, COVID -19 medically attended acute outcomes 1 –7 or 1 –21 day evaluation\n**RSVPreF  Phase 3 clinical trial electronic diary for 7 days after vaccination\nn/a = not available\n© HealthPartners 22Acute outcomes, continued\nOutcome Risk window (d) Background \nrate/10,000*\nMyocarditis / pericarditis 1–21, 1–42 0\nPulmonary embolism (PE) 1–21, 1–42 0.1\nSeizure 1–21, 1–42 0.8\nStevens -Johnson syndrome or toxic epidermal necrolysis 1–21, 1–42 0/a\nStroke, hemorrhagic 1–21, 1–42 0.4\nStroke, ischemic 1–21, 1–42 0.4\nThrombosis with thrombocytopenia syndrome (TTS) 1–21, 1–42 n/a\nThrombotic thrombocytopenic purpura (TTP) 1–21, 1–42 n/a\nTransverse myelitis 1–21, 1–42 n/a\nTrigeminal neuralgia and related disorders 1–21, 1–42 0.1\nVenous thromboembolism (VTE) 1–21, 1–42 0.4\n*Identified from unvaccinated pregnant persons, COVID -19 medically attended acute outcomes 1 –21 day evaluation\n© HealthPartners 23Previous VSD studies evaluation HDP\nVaccine IIV Tdap COVID -19 IIV in successive \npregnancies\nTime period* 6/1/2022 –7/31/2009 1/1/2010 –11/15/2012 6/1/21 – 1/31/22 1/1/2004 – \n12/31/2018\nAge of \nparticipants14–49 14–49 16–49 any\nGA at exposure any <20 weeks <20 weeks any\nHDP outcomes ICD-9 codes:\n•GHTN (642.3,\n642.9); vax ≥ 20\nweeks GA\n•Mild preeclampsia\n(642.4)\n•Severe\npreeclampsia or\neclampsia (642.5 -\n642.7)ICD-9 codes \noccurring ≥20 weeks \nGA:\n•GHTN (642.3x,\n642.9x)a\n•Preeclampsia\n(642.4x -642.8x )bICD-10 codes ≥20 \nweeks GA –2 wks \npostpartum :\n•Gestational HTN\n(O13.x)\n•Preeclampsia -\neclampsia -HELLP\nsyndrome ( O14.x,\nO15.x, and O16.x)•Preeclampsia\n(642.4x, 642.5x,\n642.7x; O11.x,\nO14.x )\n•Eclampsia (642.6x;\nO15.x)\n*may refer to vaccine administration dates, pregnancy end date, or pregnancy start date\na 642.3x, 642.4x, 642.9x = 2 outpatient or 1 inpatient diagnosis\nb 642.5x -642.7x = inpatient diagnosis\n© HealthPartners 24Inactivated Influenza Vaccine\nCitation: Kharbanda EO, Vazquez -Benitez G, Lipkind H, Naleway A, Lee G, Nordin JD; Vaccine Safety Datalink Team. Inactivated inf luenza vaccine during \npregnancy and risks for adverse obstetric events. Obstet Gynecol. 2013 Sep;122(3):659 -67. doi: 10.1097/AOG.0b013e3182a1118a. PMID: 23921876.\n© HealthPartners 25Tdap\nKharbanda EO, Vazquez -Benitez G, Lipkind HS, Klein NP, Cheetham TC, Naleway A, Omer SB, Hambidge SJ, Lee GM, Jackson ML, McCarth y NL, \nDeStefano F, Nordin JD. Evaluation of the association of maternal pertussis vaccination with obstetric events and birth outco mes. JAMA. 2014 Nov \n12;312(18):1897 -904. doi: 10.1001/jama.2014.14825. PMID: 25387187; PMCID: PMC6599584.\n© HealthPartners 26COVID -19 \nVesco KK, Denoble AE, Lipkind HS, Kharbanda EO, DeSilva MB, Daley MF, Getahun D, Zerbo O, Naleway AL, Jackson L, Williams JTB , Boyce TG, Fuller CC, Weintraub \nES, Vazquez -Benitez G. Obstetric Complications and Birth Outcomes After Antenatal Coronavirus Disease 2019 (COVID -19) Vaccinatio n. Obstet Gynecol. 2024 Jun \n1;143(6):794 -802. doi: 10.1097/AOG.0000000000005583. Epub  2024 Apr 17. PMID: 38626447; PMCID: PMC11090513.\n© HealthPartners 27IIV in successive pregnancies\n•At least 2\nsuccessive,\nsingleton births\nbetween 1/1/2004 –\n12/31/2018\nGetahun D, Liu IA, Sy LS, Glanz JM, Zerbo O, Vazquez -Benitez G, Nelson JC, Williams JT, Hambidge SJ, \nMcLean HQ, Irving SA, Weintraub ES, Qian L. Safety of the Seasonal Influenza Vaccine in 2 Successive \nPregnancies. JAMA Netw  Open. 2024 Sep 3;7(9):e2434857. doi: 10.1001/jamanetworkopen.2024.34857. \nPMID: 39298167; PMCID: PMC11413712.", "summary": "Prenatal RSVpreF  Vaccine Safety  2023 –2024 Respiratory Season The Vaccine Safety Datalink (VSD) Malini DeSilva, MD, MPH Presentation to ACIP June 25, 2025 © HealthPartners 2Vaccine Safety Datalink (VSD) •Collaborative project between  CDC and 13 integrated  healthcare organizations •Monitors safety of vaccines used  in the U.S., primarily through  observational multisite studies •Includes data on ~15.5 million  individuals across all sites  annually (~4.5% of U.S.  population) •Annual birth…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-25-26-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-06-25-26/04a-DeSilva-Mat-Peds-RSV-508.pdf", "doc_date": "2025-06-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 27}
{"title": "04b Daley Mat Peds RSV 508", "content": "Monitoring the Safety of Nirsevimab\nin Infants Birth through <8 Months\nJune 25, 2025Matthew F. Daley, MDPreliminary Results from the Vaccine\nSafety Datalink for the 2024 -2025 Season\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\n•No conflicts of interest\n•Presenting on behalf of the Vaccine Safety Datalink (VSD) teamDisclosures and Acknowledgments\nNirsevimab  Safety Surveillance Slide 2\nBackground\nSlide 3\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\n•Long -acting monoclonal antibody, licensed for prevention of lower \nrespiratory tract disease in infants caused by RSV\n•Recommendations for use:\noAll infants aged birth through <8 months (if no RSV vaccine during pregnancy)\noHigh-risk infants aged 8 -19 months\n•High efficacy in phase 3 trial, high effectiveness post -licensure\n•Severe shortage during 2023 -2024 season\n•RSV prevention ( nirsevimab  or vaccine): 72% uptake in VSDNirsevimab  Overview\nNirsevimab  Safety SurveillanceRef: 1) Muller WJ et al, N Engl J Med 2023;388(16):1533 -1534; 2) Jones JM et al, MMWR 2023;72(34):920 -925. \n3) Moline HL et al, JAMA Pediatr  2025;179(2):179 -187. 4) Irving SA et al, Pediatrics 2025;155(6):e2024070240.\nSlide 4\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\n•Across 3  randomized trials: n=3,184 received nirsevimab , n=1,284 \nreceived placebo, n=304 received palivizumab\n•Adverse events generally balanced among infants who received \nnirsevimab  versus comparator\n•Adverse events of special interest included 7 nirsevimab -exposed \ninfants with rashes, primarily papular  or maculopapular\n•No anaphylaxis, no serious hypersensitivity -type reactions reported\n•No immune complex diseases reportedNirsevimab  Safety, Clinical Trials\nNirsevimab  Safety SurveillanceRef: 1) Muller WJ et al, N Engl J Med 2023;388(16):1533 -1534. 2) Mankad VS et al, Pathogens 2024;13(6):503.\nSlide 5\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\n•Additional post -licensure safety data needed, including assessment \nof rare adverse events, and when nirsevimab  given during routine \ncare in a general patient population\n•Objective: To investigate the safety of nirsevimab , by examining pre -\nspecified adverse events among nirsevimab  recipients in the Vaccine \nSafety Datalink (VSD)\n•Nirsevimab  is a passive immunization; CDC and ACIP requested that \nVSD evaluate its safetyPost -Licensure Safety of Nirsevimab\nNirsevimab  Safety Surveillance Slide 6\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\n•Collaboration between CDC and 13 healthcare organizations\n•Observational; uses electronic health record (EHR) data\n•Has ~15.5 million individuals overall; annual birth cohort ~115,000\n•Data characteristics:\noElectronic health records, claims, immunization information systems\noDiagnoses, vaccines, medications ordered\noInpatient, emergency departments, outpatient\n•VSD applies a range of analytic methods to address confounding, \nincluding self -controlled designsVaccine Safety Datalink (VSD)\nNirsevimab  Safety SurveillanceRef: 1) McNeil MM et al, Vaccine. 2014 Sep 22;32(42):5390 -8.\nSlide 7\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\nVSD in 2025\nNirsevimab  Safety Surveillance\n Slide 8\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\n•Received nirsevimab , n=36,719\n•Adverse events monitored, self -controlled risk interval (SCRI):\noAll analyses stratified by age group (neonates; infants)\noSeizures, ITP, drug reaction, fever or sepsis (neonate cohort only)\noNone showed elevated risk\n•Exposure -dependent events: monitored case counts\noAnaphylaxis: no cases detected\noNon-anaphylactic allergic reactions: urticaria, often same day as nirsevimabSafety Results, VSD, 2023 -2024 Season\nNirsevimab  Safety Surveillance Slide 9\nMethods\nSlide 10\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\n•Setting: all VSD data -contributing sites\n•Population: all infants 0 days through <8 months of life who received \nnirsevimab  between October 1, 2024, and February 1, 2025\n•Same -day vaccines: study included all nirsevimab -exposed infants, \nregardless of whether they received vaccines same day as nirsevimab\n•Health insurance enrollment: through control window\n•Study design: primarily used SCRI\n•Excluded infants born to someone who received RSV vaccine during \npregnancyMethods Overview\nNirsevimab  Safety Surveillance Slide 11\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\n•Self-controlled risk interval is a form of self -controlled case series study\n•Commonly used design in vaccine safety studies\n•Rationale: exposed (to vaccine, or to nirsevimab ) often differ in important \ncharacteristics from unexposed; these characteristics typically not \nmeasured in electronic health record (EHR) data and can confound safety \nassessments\n•These are within -individual designs; control for measured and unmeasured \nconfounders that do not vary over time; example, a prevalent chronic \nconditionSelf-Controlled Designs in Safety Studies\nNirsevimab  Safety Surveillance Slide 12Ref: 1) Nie X et al, Expert RevVaccines 2022;21(3):313 -324. 2) Weldeselassie  YG et al, Epidemiol Infect 2011;139(12):1805 -\n17. 3) Li R et al, J Biopharm Stat 2016;26(4):686 -93. 4) Bots SH et al, Am J Epidemiol. 2025;194(1):208 -219.\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\n•Diagnoses in first month of life often related to pregnancy, delivery, \nnewborn -specific conditions\n•Health care utilization different in first month of life\n•Lags in health insurance enrollment\n•With the exception of birth dose of hepatitis B vaccine, earliest all \nother vaccines recommended: 38 days of age\n•Separate safety analyses:\noNewborns: defined as 0 days through 37 days of age\noInfants (out of newborn period): 38 days through <8 months of ageAge Effects\nNirsevimab  Safety Surveillance Slide 13\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\n•Rationale for pre -specified adverse events:\noBiologic plausibility\noClinical trial data\noExpert opinion\noFeedback from ACIP RSV Work Group\n•Identified based on ICD -10 diagnosis codes, laboratory data \n(platelet counts)Adverse Events Monitored\nNirsevimab  Safety Surveillance Slide 14\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\nOutcomes for Nirsevimab Safety Surveillance Study\nNirsevimab  Safety SurveillanceAdverse event Design\nSeizures Self-controlled risk interval\nImmune thrombocytopenia (ITP) Self-controlled risk interval\nDrug reaction Self-controlled risk interval\nFever or sepsis (neonates only) Self-controlled risk interval\nAnaphylaxis Counts monitored\nNon-anaphylactic serious allergic reaction Counts monitored\nAutoimmune, immune complex disease Outcomes rare, may have long latency; examine as \ncase -control at end of surveillance\nSlide 15\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\nSelf-Controlled: Risk and Control Windows\nNirsevimab  Safety SurveillanceAdverse eventAge at nirsevimab \nadministrationRisk \nwindow \n(days)Control \nwindow \n(days) Setting\nSeizure 0-37 days 0-7 8-21 Inpatient, ED\n38 days to <8 months 0-7 8-21 Inpatient, ED\nImmune thrombocytopenia 0-37 days 1-21 22-42 Inpatient, ED, outpatient\n38 days to <8 months 1-21 22-42 Inpatient, ED, outpatient\nDrug reaction 0-37 days 0-7 8-15 Inpatient, ED\n38 days to <8 months 0-7 8-15 Inpatient, ED\nFever or sepsis (neonates \nonly)0-37 days 0-7 8-15 Inpatient, ED\nSlide 16\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\nExposure -Dependent Events: Case Counts Monitored\nNirsevimab  Safety SurveillanceAdverse eventAge at nirsevimab \nadministrationRisk \nwindow \n(days) Setting Manual review\nAnaphylaxis 0-37 days 0-2 Inpatient, \nEDAll cases will be manually \nreviewed\n38 days to <8 months 0-2 Inpatient, \nEDAll cases will be manually \nreviewed\nNon-anaphylactic allergic \nreactions0-37 days 0-7 Inpatient, \nEDCases reviewed if \nindicated\n38 days to <8 months 0-7 Inpatient, \nEDCases reviewed if \nindicated\nSlide 17\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\nOutcomes for Nirsevimab  Safety Surveillance Study\nNirsevimab  Safety SurveillanceAdverse event ICD-10 codes Additional information\nSeizure G40, R56, P90 First episode in 30 days\nImmune \nthrombocytopeniaD69.3, D69.6, P61.0 Also required platelets <50,000; first episode in \n90 days\nDrug reaction P93, T80.22, T80.29, \nT80.8, T80.9Example: “Infection following…therapeutic \ninjection”; first episode in 30 days\nFever or sepsis \n(neonates only)P36.9, R50.82, R50.83, \nR50.9, T81.1, T81.4First episode in 30 days\nAnaphylaxis T80.5, T78.2, T88.6, P81.1 First episode in 30 days\nNon-anaphylactic serious \nallergic reactionT80.6, T78.3, L50.0, \nL50.1, L50.9, P83.88First episode in 30 days\nSlide 18\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\n•For each pre -specified outcome: \noIdentify cases that occur within either risk or control window\noTwo observations per individual: One per control window and risk \nwindow\noInformative cases have outcome in one window but not the other\noCohort must have at least one outcome in each window to estimate \neffect\n•Models stratified by age group\n•Fixed -effects Poisson regression\noIndividual: Within person comparison across windows controls for \nmeasured and unmeasured time -invariant factorsAnalytic Methods: SCRI Analysis\nNirsevimab  Safety Surveillance Slide 19\nResults\nSlide 20\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\nChildren 0 days old to < 8 months old 01OCT24 -01FEB25\n(n=117,427) \nEnrolled from at least 38 days old and at least 1 day between 01OCT24 -01FEB25\n(n=92,418, 79%)\nNirsevimab\n(n=43,532, 47%)\nNo RSV vaccine during pregnancy\n (n=41,869, 96%)\n38 days to < 8 months at index\n(n=28,208, 67%)\nAdministered prior to season\n (n=154, <1%)Administered this season \n(n=28,054, 99%)0-37 days old at index \n(n=13,661, 33%)\nAdministered this season \n(n=9,855, 81%)Administered prior to season \n(n=3,806, 19%)RSV vaccine during pregnancy \n(n=1,663, 4%)No nirsevimab  \n(n=48,886, 53%)\nNirsevimab Safety SurveillanceStudy Flow\nSlide 21\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\nDoses by \nWeek of Age\nNirsevimab  Safety SurveillanceNote :\n0 week=aged 0 -6 days\n1 week=aged 7 -13 days\nAnd so forth\nSlide 22\n\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\nNeonate \nCohort: \nDoses by \nDays of Age\nNirsevimab  Safety Surveillance Slide 23\n\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\n•Among neonates (0 -37 days old) who received nirsevimab :\noN=2,954 (20%): received on same day as hepatitis B vaccine\n•Among infants 38 days through <8 months who received nirsevimab :\noN=24,847 (84%): received on same day as vaccines\noMost common combination: nirsevimab  plus hepatitis B, rotavirus, DTaP, Hib, \npneumococcal, and polio vaccines (n=15,252)Simultaneous (Same -Day) Receipt of Vaccines\nNirsevimab  Safety Surveillance Slide 24\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\nSelf-controlled Risk Interval Results: Seizures\nNirsevimab  Safety SurveillanceAdverse \neventAge \ngroupn Risk \nwindow \n(days)Control \nwindow \n(days)N cases \nin risk \nwindowN cases \nin \ncontrol \nwindowRR 95% CI P-value\nSeizures 0-37 \ndays9,855 0-7 8-21 4 2 3.50 0.64, 19.11 0.148\n38 days \nto <8 \nmonths28,054 0-7 8-21 5 2 4.38 0.85, 22.55 0.078\n•2023 -2024 season: non -significant also; no elevated risk of seizures\nSlide 25\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\nSelf-controlled Risk Interval Results: ITP\nNirsevimab  Safety SurveillanceAdverse \neventAge \ngroupn Risk \nwindow \n(days)Control \nwindow \n(days)N cases \nin risk \nwindowN cases \nin \ncontrol \nwindowRR 95% CI P-value\nITP 0-37 \ndays9,817 1-21 22-42 0 0 N/A N/A N/A\n38 days \nto <8 \nmonths28,023 1-21 22-42 1 0 N/A N/A N/A\n•Case definition required a diagnosis, and  a platelet count below 50,000, within \n21 days of each other, taking first of 2 dates\nSlide 26\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\nSelf-controlled Risk Interval Results: Drug Reaction\nNirsevimab  Safety SurveillanceAdverse \neventAge \ngroupn Risk \nwindow \n(days)Control \nwindow \n(days)N cases \nin risk \nwindowN cases \nin \ncontrol \nwindowRR 95% CI P-value\nDrug \nreaction0-37 \ndays9,855 0-7 8-15 0 0 N/A N/A N/A\n38 days \nto <8 \nmonths28,054 0-7 8-15 0 0 N/A N/A N/A\nSlide 27\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\nSelf-controlled Risk Interval Results: Sepsis and Fever\nNirsevimab  Safety SurveillanceAdverse \neventAge \ngroupn Risk \nwindow \n(days)Control \nwindow \n(days)N cases \nin risk \nwindowN cases \nin \ncontrol \nwindowRR 95% CI P-value\nSepsis \nand fever0-37 \ndays9,855 0-7 8-15 4 9 0.44 0.14, 1.44 0.18\n•Only for newborn cohort (not conducted for 38 days to <8 months of age)\n•Additional exploratory analysis performed to assess whether nirsevimab  could \ncause fever, leading to sepsis workup (blood, CSF cultures)\noAn imbalance detected in cultures obtained in risk vs. control windows\noManual review of sample of charts showed no consistent pattern of concern (neonates \ntypically had reasons other than fever for cultures being done)\nSlide 28\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\nExposure -Dependent Events: Hypersensitivity Reactions\nNirsevimab  Safety SurveillanceAdverse event Age group n Risk \nwindow \n(days)N cases \nin risk \nwindowRate per \n10K person \nmonth\nAnaphylaxis 0-37 days 9,855 0-2 0 0\n38 days to <8 \nmonths28,054 0-2 0 0\nOther allergic \nreaction0-37 days 9,855 0-7 14 54.93\n38 days to <8 \nmonths28,054 0-7 4 5.46\n•Anaphylaxis and other allergic reactions: exposure -induced outcomes; only \nassess within potential risk windows\n•“Other allergic reaction” cases: n=17 with diagnosis code for urticaria and n= 1 \n“serum reaction” (also for urticaria); majority on same day as nirsevimab\nSlide 29\nSummary\nSlide 30\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\n•Among a population of >74,000 (across two seasons) neonates and \ninfants exposed to nirsevimab :\noNo evidence of increased risk of seizures, ITP, drug reaction, fever and sepsis\noNo cases of anaphylaxis\noSmall number of cases of non -anaphylactic allergic reactions in both years, \nprimarily coded as urticaria\n•Provides reassuring data regarding the safety profile of nirsevimab  \nwhen used in routine clinical practice\n•Additional data extraction needed for late -season nirsevimab  use; \nfindings preliminarySummary\nNirsevimab  Safety Surveillance Slide 31\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\n•Three planned assessments\noAfter 2023 -2024 respiratory season\noPreliminary assessment 2024 -2025 season (through January, presented today)\noEnd of surveillance assessment (data extraction July 2025)\n•Manual record review of any anaphylaxis cases\n•Planned case -control study of autoimmune and immune complex \ndisease; however, appear to have too few cases to study this group of \noutcomes at presentSurveillance Continues\nNirsevimab  Safety Surveillance Slide 32\nQuestions?\nSlide 33\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\nDoses by \nWeek, All \nFormulations\nNirsevimab  Safety Surveillance Slide 34\n\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\nDoses by \nWeek by \nFormulation\nNirsevimab  Safety Surveillance Slide 35\n\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\n•SmartVax  (Western Australia):\no4,340 parents texted hyperlink to report adverse events (27.5% responded)\no18 (1.5%) respondents sought medical attention within 3 days of nirsevimab\noSymptoms at presentation included gastrointestinal issues, fatigue, local \nreaction, fever, refusal to feed, unsettled behavior\noNo serious adverse events reported\n•Maternity department, French hospital\noExposed accepted nirsevimab  (n=477); unexposed declined (n=40)\noSurveyed at 2 hours, days 7, 14, 30\noMore frequent reports of regurgitation in nirsevimab -exposed on day 30Other Nirsevimab  Safety Surveillance\nNirsevimab  Safety SurveillanceRef: 1) Carcione D et al, PIDJ, 2025 (in press). 2) Ocana de Sentuary C et al, eClinicalMedicine  2025;79:102986 \nSlide 36\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\n•Misclassification of exposure: missing nirsevimab  doses\n•Misclassification of outcomes\n•Safety assessment limited to pre -specified outcomes of interest\n•Main analyses were regardless of vaccines received on same day; if \npositive safety signal, can be difficult to disentangle effect of vaccines \nfrom effect of nirsevimab\n•Although risk and control windows are short, time -varying covariates \ncould bias results\n•In a population size of >74,000, unable to assess risk of very rare \nadverse eventsStudy Limitations\nNirsevimab  Safety Surveillance Slide 37", "summary": "Monitoring the Safety of Nirsevimab in Infants Birth through <8 Months June 25, 2025Matthew F. Daley, MDPreliminary Results from the Vaccine Safety Datalink for the 2024 -2025 Season KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH •No conflicts of interest •Presenting on behalf of the Vaccine Safety Datalink (VSD) teamDisclosures and Acknowledgments Nirsevimab  Safety Surveillance Slide 2 Background Slide 3 KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH •Long -acting monoclonal antibody,…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-25-26-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-06-25-26/04b-Daley-Mat-Peds-RSV-508.pdf", "doc_date": "2025-06-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 37}
{"title": "05 MacNeil Mat Peds RSV 508", "content": "U.S. Centers for Disease Control and Prevention \nEvidence to Recommendation Framework : \nClesrovimab \nMaternal/Pediatric RSV Work Group  \nAdvisory Committee on Immunization Practices \nJune 25, 2025 \n1 \n     \n Policy Question \n• Should clesrovimab be recommended for all infants <8 months of age born\nduring or entering their first RSV season? \n2 \n \n \n  \n   \n  \n    \n        \n   \n      \n    \n   \n     \n    Evidence to Recommendation (EtR ) Framework \nEtR Domain Question(s) \nPublic Health Problem Is the problem of public health importance? \nBenefits and Harms How substantial are the desirable anticipated effects? \nHow substantial are the undesirable anticipated effects? \nDo the desirable effects outweigh the undesirable effects? \nValues Does the target population feel the desirable effects are large relative \nto the undesirable effects? \nIs there important variability in how patients value the outcome? \nAcceptability Is the intervention acceptable to key stakeholders? \nFeasibility Is the intervention feasible to implement? \nResource Use Is the intervention a reasonable and efficient allocation of resources? \nEquity What would be the impact of the intervention on health equity? \n3 \n  \n   \n EtR Domain: Public Health Problem \nIs RSV -associated disease among infants <8 months of age of public health \nimportance? \n4 \n \n \n     \n            \n       \n      \n   RSV burden is high in children <5 years of age \nEach year in the United States, RSV leads to approximately*: \n~2,000,000 medical encounters1 \n58,000– 80,000 hospitalizations1,2,3 \n100– 300 deaths4,5,6 \n*Data on the burden of RSV disease in children under 5 are from before the 2023- 2024 RSV season, when RSV prevention products became available in the US. \nReferences: 1) Hall et al, NEJM (2009): https://doi.org/10.1056/NEJMoa0804877 2) McLaughlin et al, J Infect Dis (2022): https://doi.org/10.1093/infdis/jiaa752 3) \nCDC RSV- NET, unpublished data. 4) Thompson et al, JAMA (2003): https://doi.org/10.1001/jama.289.2.179 5) Matias et al, Influenza Other Respi Viruses (2014): \nhttps://doi.org/10.1111/irv.12258 6) Hansen et al, JAMA Network Open (2022): https://doi.org/10.1001/jamanetworkopen.2022.0527 5 \n6     \n  \n     \n \n   \n \n    \n \n     \n            \n         RSV is the leading cause of hospitalization in infants1 \nIn the absence of RSV prevention products: \n• Most infants (68%) are infected in the \nfirst year of life and nearly all (97%) by age 2 years\n2 \n• 2-3% of young infants are hospitalized for \nRSV3,4,5 \n-Highest rates occur in the first months of life, \nand risk declines with increasing age in early childhood\n3,5 \n-~80% of hospitalized children have no \nunderlying medical conditions3 \n-All infants are at risk for hospitalization \nReferences: 1) Suh et al, JID (2022): https://doi.org/10.1093/infdis/jiac120 2) Glezen et al, Arch Dis Child (1986): https://doi.org/10.1001/archpedi.1986.02140200053026 3) Hall et al, Pediatrics (2013): \nhttps://doi.org/10.1542/peds.2013- 0303 4) Langley et al, PIDJ (2011): https://doi.org/10.1097/INF.0b013e3182184ae7 5) Curns et al, Pediatric s (2024): https://doi.org/10.1542/peds.2023- 062574 6 \n   \n     \n   Public Health Problem -Work Group Interpretation \n• Is RSV -associated disease among infants <8 months of age of public\nhealth importance? \nNo Probably \nNo Probably \nYes Yes Varies Don’t \nknow \n7 \n   \n  \n  \n EtR Domain: Benefits and Harms \nHow substantial are the desirable anticipated effects? \nHow substantial are the undesirable anticipated effects? Do the desirable effects outweigh the undesirable effects? \n8 \n \n        \n  \n \n     \n  \n     \n  \n   \n \n     GRADE: PICO Question \nPopulation All infants <8 months of age born during or entering their first RSV season \nIntervention Clesrovimab \nComparison No immunization \nOutcomes Benefits \nPrevention of: \n1. RSV-associated medically attended lower respiratory tract infection (LRTI) \n2. RSV-associated LRTI with hospitalization \n3. RSV-associated LRTI with intensive care unit admission \n4. All-cause medically attended LRTI \n5. All-cause LRTI with hospitalization \nHarms \n1. Serious adverse events \nAbbreviations: GRADE: Grading of Recommendations, Assessment, Development and Evaluation 9 \n      \n \n  \n       \n   \n       \n  \n        \n       \n       \n     \n       \n     \n   \n               \n       \n     Interpreting a GRADE certainty assessment \n• A certainty assessment reflects our confidence that the true effect lies close to the \nestimated effect \n• There are 4 certainty levels: \n• High: We are very confident that the true effect lies close to that of the estimated effect. Randomized controlled \ntrial certainty starts here and can be downgraded or upgraded1. \n• Moderate: We are moderately confident that the true effect lies close to the estimated effect, but there is a \npossibility that it is substantially different. \n• Low: We have limited confidence that the true effect lies close to the estimated effect; the true effect may be \nsubstantially different from the estimated effect. Observational certainty starts here and can be downgraded or \nupgraded1. \n• Very low: We have very limited confidence that the true effect lies close to the estimated effect; the true effect \nis likely to be substantially different from the estimated of effect. \n• A certainty assessment does not reflect our confidence in the quality of the individual \nst\nudies or the overall confidence in benefits and harms of the vaccine, which may be \ninformed by additional data. \n1) Evidence type may be downgraded due to risk of bias, inconsistency, indirectness, imprecision or other considerations such as publication bias and upgraded for indications of a dose -response \ngradient, large or very large magnitude of effect, and opposing residual confounding. \nAbbreviations: GRADE: Grading of Recommendations, Assessment, Development and Evaluation 10 \n  \n  \n  \n    \n  \n  \n  \n      \n      \n      \n  \n          \n    GRADE: Outcomes, importance, and data sources \nOutcome Importance1 Data sources \nBenefits \n1. RSV -associated medically attended LRTI Critical Phase 2b/3 RCT2 \n2. RSV -associated LRTI with hospitalization Critical Phase 2b/3 RCT2 \n3. RSV -associated LRTI with ICU admission Critical Phase 2b/3 RCT2 \n4. All -cause medically attended LRTI Important Phase 2b/3 RCT2 \n5. All -cause LRTI with hospitalization Important Phase 2b/3 RCT2 \nHarms \n6. Serious adv\nerse events Importan\nt Phase 2b/3 \nRCT2 \n1. Three options: Critical; Important but not critical; Not important for decision making \n2. Protocol 004: A Phase 2b/3 Double -Blind, Randomized, Placebo- Controlled Study to Evaluate the Efficacy and Safety of Clesrovimab in Healthy \nPreterm and Full -Term Infants – described in Zar et al., Open Forum Infectious Diseases (2025): https://doi.org/10.1093/ofid/ofae631.003 ; Sinha, \npresentation to ACIP (2024): https://www.cdc.gov/acip/downloads/slides -2024- 10-23-24/02- RSV-Mat-Peds -Sinha -508.pdf ; and unpublished data \nfrom manufacturer Abbreviations: GRADE: Grading of Recommendations, Assessment, Development and Evaluation | LRTI: Lower respiratory tract infection | \nRCT: randomized controlled trial | ICU: intensive care unit \n11 \nGRADE Benefits : Efficacy estimates and concerns in \nOutcome Efficacy estimate1\n% (95% CI) Concerns in certainty assessment \n1. RSV -associated medically attended LRTI 60.4 (44.1, 71.9) Not serious (indirectness)2 \n2. RSV -associated LRTI with \nhospitalization 90.9 (76.2, 96.5) Not serious (indirectness)2 \n3. RSV LRTI with ICU admission3 100.0 (24.0, 100.0) Serious (imprecision)4 \nNot serious (indirectness)2 \n4. All -cause medically attended LRTI 13.1 ( -0.6, 24.8) Serious (imprecision)5 \nNot serious (indirectness)2  \n  \n  \n   \n  \n  \n   \n \n  \n       \n             \n    \n         \n     \n            \n     certainty assessment \nBenefits, through 150 days of follow- up \n5. All-cau\nse LRTI with hospitalization 49.0 (26.7, \n64.5) Not ser\nious (indirectness)2 \n1. Esti\nmates and 95% CI were estimated from the modified Poisson regression with robust variance method. \n2. Concern for indirectness: the trial excluded infants who were palivizumab -eligible and took place during a season with disrup ted seasonality due to COVID -19. This was \ndeemed not serious. \n3. Outcome was not a trial endpoint and was assessed post- hoc. \n4. Serious concern for imprecision: the number of study participants did not meet optimal information size. \n5. Serious concern for imprecision: the confidence interval containing estimates for which different policy decisions might be considered. \nAbbreviations: GRADE: Grading of Recommendations, Assessment, Development and Evaluation | CI: confidence interval | LRTI: lower respiratory tract infection | RCT: \nrandomized controlled trial | ICU: intensive care unit 12 \n     \n \n \n \n \n               \n \n          \n     \n           \n      GRADE Harms : Relative risk of serious adverse events \n(SAEs) and concerns in certainty assessment, days 1 -\n365 post immunization \nOutcome Relative risk1 (95% CI) Concerns in certainty assessment \nHarms \nSeri\nous adverse events (SAEs)2 0.93 (0.77, 1.12) Ser ious (imprecision)3 \n1. Relative risk was calculated as the risk of a serious adverse event in the clesrovimab arm divided by the risk of a serious adverse \nevent in the placebo arm. \n2. Adverse event resulting in death, hospitalization, significant disability, or requiring medical intervention. Serious adverse ev ents \nmay be related or unrelated to the study intervention. \n3. Serious concern for imprecision: too few infants were included in the trial to capture rare events. \nAbbreviations: GRADE: Grading of Recommendations, Assessment, Development and Evaluation | CI: confidence interval 13 \n  \n        ​\n  ​​\n​\n     \n   \n \n    \n   \n     \n​     \n   Summary of GRADE for clesrovimab \nOutcome Importance Design \n(# of studies) Findings Evidence type \nBenefits \n1. RSV -associated \nmedically attended LRTI Critical RCT (1) Clesrovimab is effective in preventing RSV -associated \nmedically attended LRTI High \n2. RSV -associated LRTI \nwith hospitalization Critical RCT (1) Clesrovimab is effective in preventing RSV -associated LRTI \nwith hospitalization High \n3. RSV -associated LRTI \nwith ICU admission Critical RCT (1) Clesrovimab is effective in preventing LRTI with ICU \nadmission Moderate \n4. All -cause medically \nattended LRTI Important RCT (1) Clesrovimab is not effective in preventing all cause medically attended LRTI Moderate \n5. All -cause LRTI with \nhospitalization Important RCT (1) Clesrovimab is moderately effective in preventing all cause hospitalization with LRTI High \nHarms \n6. Serious adverse events Important RCT (1) Serious adverse events were balanced between the \nclesrovimab group and the placebo group Moderate \nAbbreviations: LRTI: Lower respiratory tract infection | RCT: randomized control trial | ICU: intensive care unit | serious adverse events 14 \n      \n \n   \n         \n  \n   Additional benefits of clesrovimab not included in GRADE: \nEfficacy for RSV -associated medically -attended LRTI and \nhospitalization observed through 180 days \nOutcome Follow- up time: 150 days Follow- up time: 180 days \nEvents/ \nClesrovimab (n/N) Events/ Placebo (n/N) Efficacy estimate % (95% CI) Events/ Clesrovimab (n/N) Events/ Placebo (n/N) Efficacy estimate % (95% CI) \nRSV-associated \nmedically attended LRTI 60/2398 74/1201 60.4 (44.1, 71.9) 64/2398 77/1201 59.5 (43.3, 71.1) \nRSV-associated LRTI with \nhospitalization 5/2398 27/1201 90.9 (76.2, 96.5) 5/2398 28/1201 91.2 (77.2, 96.6) \nAbbreviations: LRTI: lower respiratory tract infection | CI: confidence interval 15 \n   \n      \n      \n     \n \n   \n \n   \n              \n          \n         \n   Additional benefits of clesrovimab not included in \nGRADE \n• If recommended by CDC, there will be two approved1 and recommended2 \nlong-acting monoclonal antibodies for prevention of severe RSV disease in \ninfants \n• Multiple products with different binding sites are beneficial if resistance \nmutations develop to either product \n• Multi\nple manufacturers in the same market allow for: \n-If one product has insufficient supply in the United States, the other product \nre\nduces the risk of a shortage.3 \n-Competitive pricing of products may be created by market competition \n1. In July 2023, the Food and Drug Administration (FDA) approved nirsevimab for the prevention of RSV –associated lower respirato ry tract infection among infants and children aged <24 \nmonths. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761328s000lbl.pdf and 2. In August 2023, the Advisory Committee for Immunization Practices recommended \nnirsevimab infants aged <8 months born during or entering their first RSV season and for infants and children aged 8 –19 months who are at i ncreased risk of severe RSV disease entering \ntheir second RSV season. https://www.cdc.gov/mmwr/volumes/72/wr/mm7234a4.htm ; 3. https://www.cdc.gov/han/2023/han00499.html 16 \n  \n   \n  \n \n     \n    \n     \n \n \n     Additional harms of clesrovimab not included in \nGRADE: Solicited adverse events (AEs), days 1 –5 post\nimmunization \n• Injection -site and systemic reactions were comparable between the \nclesrovimab (29.9%) and placebo (30.9%) arms \n-Irritability and somnolence were the most commonly reported solicited AEs \n• Mostly Grade 1 (mild) or 2 (moderate) \n-The proportions of participants with solicited AEs of Grade 3 (severe) were low \n(≤\n0.2%) in both groups \n-No Grade 4 (potentially life -threatening) solicited AEs \nNotes: Grade 1= mild; Grade 2= moderate; Grade 3=severe; Grade 4=potentially life threatening; https://www.fda.gov/media/73679/download 17 \n   \n  \n \n \n         \n Additional potential harms of clesrovimab not \nincluded in GRADE: Fever*, days 1 –5 post\nimmunization \n• Rates of fever were comparable between the clesrovimab (3.7%) and \nplacebo (4.0%) arms \nStudy Events*/Clesrovimab Events*/Placebo \n(n/N) (n/N) \nProtocol 004 89/2408† (3.7%) 48/1202 (4.0%) \n*Fever defined as a temperature ≥ 100.4 °F \n† Total N=2409; 2408 had temperature data available per communication with manufacturer on March 9, 2025 \n18 \n   \n   \n   \n     \n    \n      \n \n       Work group interpretation of benefits and harms of \nclesrovimab \nBenefits \n• Efficacious long -acting, monoclonal antibody that can prevent severe RSV \ndisease in young infants during the duration of their first RSV season \n• Second long -acting, monoclonal antibody RSV prevention product would \nmitigate the risk of manufacturing shortages and loss of efficacy due to  \nmutations in the binding site. \nHarms \n• Favorable safety profile with no observed increase in serious adverse events, \nlocal or systemic reactions, including fever \n• Rare serious adverse events unlikely to be detected in a trial due to sample \nsize \n19 \n   \n    \n   Benefits and Harms \n• How substantial are the desirable anticipated effects? \n-How substantial are the anticipated effects for each main outcome for \nwhich there is a desirable effect? \nMinimal Small Moderate Large Varies Don’t know \n20 \n   \n    \n   Benefits and Harms \n• How substantial are the undesirable anticipated effects? \n-How substantial are the anticipated effects for each main outcome for \nwhich there is an undesirable effect? \nMinimal Small Moderate Large Varies Don’t know \n21 \n   \n \n Benefits and Harms \n• Do the desirable effects outweigh the undesirable effects? \nFavors intervention (clesrovimab) \nProbably favors the intervention (clesrovimab) \nProbably favors the comparison (no \nimmunization) \nFavors the comparison (no immunization) \nUnclear \n22 \n \n    \n \n     \n  EtR Domain: Values \nDo parents and caregivers feel that the desirable effects of clesrovimab are large \nrelative to the undesirable effects? \nIs there important uncertainty about, or variability in, how much parents and \ncaregivers value the prevention of severe RSV disease? \n23 \n    \n   \n     \n    \n \n     \n  \n   \n  \n    RSV risk perceptions and knowledge among pregnant \nwomen in the U.S. (n=523), December 2022- January 2023 \nIn a nationwide, online survey of women who were pregnant or < 12 months \npostpartum: \n• 31% of respondents reported knowing a baby who had been hospitalized for \nRSV \n• 40% of respondents believed that their own baby would be moderately or \nseverely ill if infected with RSV \n• 69% of respondents were worried their baby would need to be hospitalized if infected with RSV \nReference: Gidengil et al, Open Forum Infect Dis. (2023): https://doi.org/10.1093/ofid/ofad500.1467 24 \n    \n                 \n      \n \n  Parents do not have a clear preference among RSV\nimmunization products \nParental preference for RSV immunization products if both were available, safe and effective \namong adults aged 18-49 years with children, CASCADIA Study, Oregon and Washington, U.S., \nApril-May 2023 (n=1082) \n37% \n12% \n3% 48% Maternal RSV vaccine \nLong-acting monoclonal antibody \nNeither No preference \nSource: Kuntz et al. Attitudes about Respiratory Syncytial Virus (RSV) Vaccination during Pregnancy, and Infant Monoclonal Antibodies for RSV, 2024 25 \n– - -  \n  \n                   \n                      \n               \n                 \n                    \n       \n       \n       \n      \n \n \n \n  \n  \n  \n  50% of women 18-49 years who have an infant <8 months \nreceived a long -acting monoclonal antibody \nInfant protection against RSV by maternal RSV vaccination* or receipt of nirsevimab †, and \nintent ‡ for nirsevimab receipt by women aged 18– 49 years who have an infant <8 months \nduring the RSV season (born since April 1, 2024), February 2025, United States \nMother received RSV vaccination \nduring pregnancy \nInfant received nirsevimab \nDefinitely will get nirsevimab for \ninfant \nProbably will get nirsevimab for \ninfant or unsure \nProbably or definitely will not get \nnirsevimab for infant \n*Receipt of RSV vaccination during pregnancy was assessed by the NIS –ACM questionnaire among women 18 –49 years who reported having an infant born since October 1, 2024. For infants born April 1, 2024, through September 30, 2024, maternal RSV \nvaccination was not assessed, and these infants were assumed to be protected against RSV only if infant was reported to have received nirsevimab. The estimates of receipt of RSV vaccination during pregnancy for infants born since April 1, 2024 are not a n \nassessment of maternal RSV vaccination coverage among pregnant women eligible for vaccination as shown with the Vaccine Safety Datalink , as they are based on all infants eligible for nirsevimab or maternal vaccination rather than eligible pregnancies \n†Estimates of nirsevimab receipt by infants born since April 1, 2024, include those who were born shortly before or are enter ing their first RSV season and do not account for the mother's RSV vaccination status during pregnancy \n‡Intent for nirsevimab receipt is assessed among infants who had not received nirsevimab and whose mother did not receive RSV vaccination during pregnancy. Estimates of nirsevimab intent among women interviewed in August and September 2024 \nincluded all women who reported having an infant <8 months, and could include infants born in February and March 2024. \nData Source: National Immunization Survey Adult COVID Module https://www.cdc.gov/rsvvaxview/dashboard/nirsevimab coverage infants.html 26 \n     \n \n   \n  Values \n• Do parents and caregivers feel that the desirable effects of clesrovimab\nare large relative to the undesirable effects? \nNo Probably \nNo Probably \nYes Yes Varies Don’t \nknow \nMajority opinion Minority opinion 27 \n        \n     \n  \n  \n   \n  \n  Values \n• Is there important uncertainty about, or variability in, how much\nparents and caregivers value the prevention of severe RSV disease? \nImportant uncertainty or variability \nP\nrobably important uncertainty or variability \nP\nrobably not important uncertainty or variability \nN\no important uncertainty or variability \nN\no known undesirable outcomes \nMajority opinion Minority opinion \n28 \n \n   EtR Domain: Acceptability \nIs clesrovimab acceptable to key stakeholders? \n29 \n \n              \n      \n             \n \n \n    \n        Pediatrician attitudes regarding long -acting \nmonoclonal antibody \nPediatrician attitudes about nirsevimab, Pediatrician survey*, October 2024, n=200 \n91 94.5 \n7 95.5 96.5 \n4 \n4.5 3 0.5 \nNirsevimab is safe for infants \n0.5 \nNirsevimab is effective against severe RSV disease in infants \nStrongly agree or agree \n1 Neither agree nor disagree \nI feel confident discussing and recommending nirsevimab Disagree or strongly disagree immunization with my patient's parents/caregivers \n2 \nI feel comfortable co-administering nirsevimab and one or more \nvaccines to my pediatric patients in one visit. \n0% 20% 40% 60% 80% 100% \n• 77% of pediatricians reported that their practice had ever offered nirsevimab \n• The majority of pediatricians agreed that nirsevimab is safe for infants and effective against severe \ndisease in infants \n*Porter Novelli View Points Health Care Practitioner survey was conducted from October 2 -10, 2024, among 200 U.S. pediatricians who reported of fering at least some routine pediatric vaccines \nto patients 30 \nReference : Kang et al, CDC (2024); https://www.cdc.gov/rsvvaxview/publications/rsv -immunization -survey -2024.html \n \n  \n  \n  RSV prevention through long -acting, monoclonal\nantibodies endorsed by national organizations \n• N irsevimab is recommended by \n-American Academy of Pediatrics1 \n-American Academy of Family Physicians2 \n-National Foundation for Infectious Diseases3 \n1) https://publications.aap.org/redbook/resources/25379/AAP -Recommendations -for-the-Prevention -of-RSV?autologincheck=redirected \n2) https://www.aafp.org/news/health -of-the-public/rsv -antibody -aafp- approval.html \n3) https://www.nfid.org/resource/contagious- chronicles -updated- recommendations -for-respiratory- season/ 31 \n  \n  \n  Acceptability \n• Is clesrovimab acceptable to key stakeholders? \nNo Probably \nNo Probably \nYes Yes Varies Don’t know \nMajority opinion Minority opinion 32 \n \n     \n  EtR Domain: Feasibility \nIs clesrovimab feasible to implement among all infants <8 months of age\nborn during or entering their first RSV season? \n33 \n      \n \n \n      \n  \n  \n   \n       \n    \n    \n   Implementation and access \n• The Vaccines for Children (VFC) program is a federally -funded program that \nprovides immunizations at no cost to children who might not otherwise be \nimmunized because of inability to pay.1 \n-If ACIP votes to include clesrovimab in VFC, it will be the second monoclonal \nantibody to be included in the VFC program. \n• I mplementation pros and cons: \n-Pro: Clesrovimab is a single dose regardless of weight \n-Con: Stocking clesrovimab may be challenging for providers who also need to \nstock nirsevimab for high -risk children 8 through 19 months entering their second \nRSV season and prefer to stock a single RSV monoclonal antibody \n1. CDC. Vaccines for Children . https://www.cdc.gov/vaccines -for-children/about/index.html 34 \n7.8 10.9 13 23.9 2020.1 19.6 21.4 28.6 30.5 27.9 39.1 30.5 26 45.7 38.3 4447.4 \n    \n         \n        \n \n \n         \n  Frequency of main challenges* pediatricians reported or \nanticipated in offering long-acting monoclonal antibody, \nPediatrician survey, October 2024 (n=200) \nParent/caregiver concerns around nirsevimab safety 32.6 \n33.5 Challenges knowing maternal RSV vaccination status to determine infant eligibility 17.4 \nFinancial burden in purchasing of nirsevimab** \nChallenges with reimbursement from private health insurance plans \n24.5 Lack of demand from parents/caregivers 10.9 \n20Challenges deterimining infant eligibility*** 15.2 \nParent/caregiver concerns around nirsevimab effectiveness \n15.5 Challenges with Medicaid reimbursement \n7.5 7.8 6.5 Supply/stock issues \n8.5 Practice  does not ha  ve or does not anticipate having  challenges in o  ffering nirsevimab \nAll pediatricians (n=200) Pediatricians whose practice had ever offered nirsevimab (n=154) Pediatricians whose practice had never offered nirsevimab (n=46) \n*R\nespondents were instructed to select up to 3 response categories \n** Private stock of nirsevimab for practices participating in the VFC (Vaccines for Children) program \n*** Challenges knowing whether infant received nirsevimab at a birthing hospital Kang et al , https://www.cdc.gov/rsvvaxview/publications/rsv -immunization -survey -2024.html 35 \n    \n    \n  Feasibility \n• Is clesrovimab feasible to implement among all infants <8 months of\nage born during or entering their first RSV season? \nNo Probably \nNo Probably \nYes Yes Varies Don’t know \nMajority opinion Minority opinion \n36 \n \n    EtR Domain: Resource Use \nIs clesrovimab a reasonable and efficient allocation of resources? \n37 \n             \n \n        \n          \n            \n  \n  \n  \n  \n   \n  RSV-associated outcomes averted: 50% coverage with\nclesrovimab among an annual US birth cohort1 \nComparison Outpatient \nVisits Averted ED Visits Averted Hospital Admissions Averted ICU Admissions Averted Deaths Averted QALYs Gained \nClesrovimab\n2 vs. no RSV \nimmunizations for most \ninfants3 121,022 43,480 20,198 4,444 20 3,413 \n1. Estimates provided by an updated UM- CDC model, where updates included VE and cost/dose. Original model and methods described her e: Hutton et al, Pediatrics (2024): \nhttps://doi.org/10.1542/peds.2024- 066461 \n2. Clesrovimab has 50% coverage, and includes 50% palivizumab use for eligible high -risk babies that do not get clesrovimab \n3. “No RSV immunizations for most infants \" means the only RSV immunization is palivizumab for eligible high -risk infants \nAbbreviations: ED: emergency department | ICU: intensive care unit | QALY: quality adjusted life year 38 \n    \n  \n \n     \n  \n    \n             \n    \n        \n          \n          Incremental cost effectiveness ratios (ICERs): 50% \ncoverage with clesrovimab among an annual US birth \ncohort1 \nComparison $/Outpatient \nVisit Averted $/ED Visit Averted $/Hospital Admission Averted $/ICU Admission Averted $/Death Averted $/QALY Gained \nClesrovimab\n2 vs. no \nRSV i mmunizations for \nmost infants3 2,948 8,207 17,666 80,300 17,666,032 104,543 \n1. Estimates provided by an updated UM- CDC model, where updates included vaccine efficacy, vaccine efficacy waning trajectory, and cost/dose. Original model and methods described here: \nHutton et al, Pediatrics (2024): https://doi.org/10.1542/peds.2024- 066461 \n2. Clesrovimab has 50% coverage, and includes 50% palivizumab use for eligible high -risk babies that do not get clesrovimab \n3. “No RSV immunizations for most infants \" means the only RSV immunization is palivizumab for eligible high -risk infants \nAbbreviations: ED: emergency department | ICU: intensive care unit | QALY: quality adjusted life year 39 \n  \n \n   \n  \n   \n \n  \n  \n  Incremental Cost -Effectiveness Ratio ($/QALY gained) \n$0 $50,000 $100,000 $150,000 $200,000 $250,000 \nDisease-Specific Inpatient Costs (per Inpatient Case) \nRSV QALYS Lost \nClesrovimab cost/dose \nProportion of Outpatient Visits With an LRTI Diagnosis Age 0-5 Months \nProportion of Hospitalizations With an LRTI Diagnosis Age 0-5 Months \nProportion of Outpatient Visits With an LRTI Diagnosis Age 6-11 Months \nFraction Receiving Palivizumab Natural History \nOutpatient Efficacy \nRSV Mortality Per Hospitalization Age 0-5 Months \nEfficacy 6-10 months \nLow High Base case: ~$105,000 $/QALY gained    \n    \n            \n \n      One -way sensitivity analysis: 50% coverage with\nclesrovimab among an annual US birth cohort1 \n1. Estimates provided by an updated UM- CDC model, where updates included VE and cost/dose. Original model and methods described her e: Hutton et al, Pediatrics (2024): \nhttps://doi.org/10.1542/peds.2024- 066461 \nAbbreviations: QALY : quality adjusted life year | LRTI: lower respiratory tract infection 40 \n \n     \n        \n       \n  \n  \n    Resource Use \n• Is clesrovimab use among infants under 8 months of age born during or\nentering their first RSV season a reasonable and efficient allocation of\nresources with an estimated cost of $458 on average ($365 VFC / $560 \nother) per dose? \nNo Probably \nNo Probably \nYes Yes Varies Don’t know \nMajority opinion Minority opinion \nAbbreviations: VFC: Vaccines for Children 41 \n EtR Summary \n42 \n  \n   \n  \n   \n  \n   \n   ​   \n     Work group considerations and interpretation \n• Phase 2b/3 trial demonstrated high efficacy for prevention of severe RSV disease \nthrough 150 days \n• Serious adverse events appeared balanced between the clesrovimab and placebo \narms; however, rare adverse events are unlikely to be detected in a trial of this \nsize \n• Work group discussion also highlighted: \n• Clesrovimab has demonstrated a shorter half- life than nirsevimab (44 days1 vs 71 days2) \nthough efficacy against severe RSV appeared sustained through 150 days \n• Clesrovimab and nirsevimab trial outcomes had different definitions , making direct comparisons in \nefficacy challenging \nReferences 1) FDA prescribing information for clesrovimab: https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/761432s000lbl.pdf 2) FDA prescribing information for \nNirsevimab: ihttps://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761328s000lbl.pdf 43 \n    \n  \n  \n   \n    \n   \n      \n   \n     Work group considerations and interpretation, \ncontinued \n• The work group highlighted the benefits of multiple long -acting RSV \nantibody products and multiple manufacturers, including: \n-If RSV develops resistance to one product or one product has insufficient supply, \nanother is available \n-Potential for decrease in price \n• T he leading cause of hospitalization in infants (RSV) can be prevented\nthrough immunization. However, for RSV immunizations to have public\nhealth impact, they must be administered early: \n-For infants born o utside the  RSV season, high uptake prior to season onset is \ncritical \n-For infants born dur\ning the\n RSV season, administration should be within the first \nweek of life -ideally during the birth hospitalization \n44 \n \n \n    Evidence to Recommendations Framework \nSummary \n• What is the balance between the desirable effects relative to the undesirable effects? \nBalance of \nconsequences Undesirable \nconsequences \nclearly \noutweigh \ndesirable \nconsequences \nin most settings Undesirable \nconsequences \nprobably \noutweigh \ndesirable \nconsequences \nin most settings The balance \nbetween \ndesirable \nand undesirable \nconsequences \nis closely \nbalanced or \nuncertain Desirable \nconsequences \nprobably \noutweigh \nundesirable \nconsequences \nin most settings Desirable \nconsequences \nclearly \noutweigh \nundesirable \nconsequences \nin most settings There \nis insufficient \nevidence \nto determine \nthe balance of \nconsequences \n45 \n \n   \n \n \n      \n Evidence to Recommendations Framework \nSummary \n• Should clesrovimab be recommended for all infants <8 months of age born during or \nentering their first RSV season? \nType of \nrecommendation We do not \nrecommend the \nintervention We recommend \nthe intervention for \nindividuals based on \nshared \nclinical decision -\nmaking We recommend \nthe intervention \n46 \n \n \n \n \n Acknowledgements \nMaternal/Pediatric RSV Work Group \nCoronavirus and Other Respiratory Viruses Division Immunization Services Division RSV-NET \nNIS- ACM \n47 \n  \n    \n            \n     For more information, contact CDC \n1-800- CDC- INFO (232- 4636) \nTTY: 1 -888- 232- 6348  www.cdc.gov \nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. \n48 \n\nBack -up \n49 \n            \n    \n  RSV-associated hospitalization rates are highest in \ninfants less than 8 months \nRate of RSV -associated hospitalization by month of life among children age <2 years, December 2016 –September 2020, \n40 New Vaccine Surveillance Network (NVSN) \n31.2 35 \n30 25 20 15 10 \n5 0 \n0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 <24 \nMonth of Life 17.7 22.4 \n15.7 \n13.7 \n11.0 \n9.6 \n8.0 \n7.4 8.8 \n6.0 6.0 6.3 \n5.0 5.8 5.4 \n4.0 3.7 3.7 3.4 2.8 2.1 1.8 2.9 8.5 Hospitalization Rate per 1,000 Children \nReference: Curns et al, Pediatric s (2024): https://doi.org/10.1542/peds.2023- 062574 50 \n2024–2025 RSV seasonality has returned to pre-\npandemic trends \nPercentage* of polymerase chain reaction (PCR) test results positive for respiratory syncytial \nvirus (RSV)**, by epidemiologic week — National Respiratory and Enteric Virus Surveillance \nSystem, United States, July 2009– June 2025 \nPre-COVID -19 \npandemic \nseasonality \n(2009-2019) \nshown by grey \nshaded area   \n   \n                     \n         \n    \n     \n       \n       \n  \n \n \n \nNotes: Report was last updated on 6/17/2025. \n*All results presented are from polymerase chain reaction (PCR) tests, which represent >90% of the diagnostic tests reported to NREVSS. The last three weeks of data in 2024 -25 may be less complete. NREVSS is an abbreviation for the National Respiratory \nand Enteric Virus Surveillance System. For more information on NREVSS, please visit National Respiratory and Enteric Virus Surveillance System | CDC . \n**Respiratory syncytial virus types A and B are not shown separately in this report. \n***The NREVSS surveillance season runs from the first week in July through June of the following year. \nAbbreviations: %+: percent positive 51", "summary": "U.S. Centers for Disease Control and Prevention  Evidence to Recommendation Framework :  Clesrovimab  Maternal/Pediatric RSV Work Group   Advisory Committee on Immunization Practices  June 25, 2025  1         Policy Question  • Should clesrovimab be recommended for all infants <8 months of age born during or entering their first RSV season?  2                                                            Evidence to Recommendation (EtR ) Framework  EtR Domain Question(s)  Public Health Problem…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-25-26-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-06-25-26/05-MacNeil-Mat-Peds-RSV-508.pdf", "doc_date": "2025-06-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 51}
{"title": "06 MacNeil Mat Peds RSV 508", "content": "Work group considerations and \nclinical considerations for clesrovimab\nMaternal and Pediatric RSV Session\nCoronavirus and Other Respiratory Viruses Division\nJune 25, 2025U.S. Centers for Disease Control and Prevention\n\n•Work group considerations and interpretations of uptake, safety, \neffectiveness, and impact studies\n•Review of clinical considerations\n-Clesrovimab recommendations compared with nirsevimab\n-Clesrovimab storage, handling, and administrationOutline\n2\n•Nirsevimab was effective against RSV -associated emergency \ndepartment encounters, hospitalization, and critical illness among infants in \ntheir first RSV season\n•Maternal vaccination was effective against RSV -associated ED encounters \nand hospitalizations\n•An estimated 57% of infants were either born to vaccinated mother \norreceived nirsevimab\n•Compared with prior to RSV immunization introduction, RSV -associated \nhospitalization rates were reduced by ~30 –40% among eligible infants and \nby half among infants aged 0 –2 monthsSummary of RSV immunization effectiveness, uptake, \nand impact for the 2024 -25 RSV season\n3\n•The impact of RSV immunizations to decrease severe RSV disease in infants \nduring the 2024 –25 RSV season in the RSV -NET and NVSN networks is clear1\n•Increasing uptake is important in order to  further reduce burden of RSV \ndisease\n-Higher impact has been seen in other countries that have attained higher uptake \nof these immunizations2–6\n-Important to maximize availability of RSV immunizations, including providing \ninfant RSV antibody during birth hospitalization\n-The increase in birthing hospital enrolled in the Vaccine For Children (VFC) \nprogram is important, but challenges remain\n Workgroup considerations on RSV immunization \neffectiveness, uptake, and impact\nRSV-NET RSV -Associated Hospitalization Surveillance Network; NVSN: New Vaccine Surveillance Network \n1Patton 2025 MMWR 2 Bloomfield 2025 Medical Journal of Australia ;3Dessers 2025 Belgian Journal of Paediatrics ; 4García‐García 2025 Influenza and Other Respiratory Viruses ; 5Ares -Gomez 2024 \nLancet ID ; 6Mazagatos 2024 Influenza Other Respir Viruses ; 4\n•During the reporting period since approval until March 31, 2025, the most \nfrequently reported adverse events involved patients who developed RSV \ninfections despite prior receipt of nirsevimab, and included signs, \nsymptoms, or complications of these infections (e.g., bronchiolitis).\n•No product safety labeling updates have been made since serious \nhypersensitivity reactions with nirsevimab were added on February 23, \n2024.\n•No additional safety signals have been identified at this time.\n•Errors involving incorrect nirsevimab dose or incorrect product (e.g., adult \nvaccine being given to infant) continue to be reported.\n•FDA will continue routine pharmacovigilance for nirsevimab. Summary of FAERS1 postmarketing  adverse events and \nmedication errors reporting with nirsevimab\n1FDA Adverse Event Reporting System (FAERS) Database | FDA 5\n•Study of 37,909 infants that received nirsevimab  during 2024 -2025 season \nusing self -controlled risk interval\n•No increased risk observed for seizures, immune thrombocytopenia (ITP), \ndrug reactions, sepsis, or fever\n•No cases of anaphylaxis and 18 (~0.05% of doses) cases of allergic reaction \nreported, primarily hivesSummary interpretation of Vaccine Safety Datalink \nnirsevimab study\n6\n•FAERS and VSD safety data are reassuring\n•Continued monitoring of safety importantWorkgroup interpretation of nirsevimab safety\nFAERS: FDA Adverse Event Reporting System; VSD: Vaccine Safety Datalink; CSF: cerebrospinal fluid 7\n•Matched cohort with ~14,000 pairs of vaccinated -unvaccinated pregnant \nwomen\n•No increased risk observed for most outcomes, including fever, fatigue, \nstroke, seizure, Bell’s palsy, ITP , pulmonary embolism, preterm birth, infant \nbeing born small for gestational age, stillbirth\n•Association of maternal RSV vaccine and HDP overall (adjusted odds ratio \n[aOR]: 1.09 [95% CI, 1.03 –1.15]) and preeclampsia ( aOR: 1.12 [95% CI, \n1.03 –1.21])\n-Severity of HDP similar among vaccinated and unvaccinated\n-Potential residual confounding (e.g., including parity in the propensity matching) \nand outcome misclassification due the difficulty in determining the timing of \nwhen HDP first occurs and lack of chart reviewVaccine Safety Datalink maternal vaccine study \nsummary\nITP: Immune Thrombocytopenic Purpura; HDP: hypertensive disorders of pregnancy 8\n•Overall study findings were reassuring, including lack of association of \npreterm birth and vaccination\n•WG continues to feel that the benefits of maternal RSV vaccination clearly \noutweigh the potential risks\n•WG was split on importance of the association of vaccination and HDP\n-Some were concerned that an imbalance of HDP was seen in multiple studies \n(phase 3 clinical trial, published retrospective cohort study, postmarketing  study), \nand felt it was important that healthcare providers discuss the potential risk of \nHDP with pregnant women\n-Some were not concerned about this association since the effect size was small, \nand there was no increased severity in vaccinated vs. unvaccinated women with \nHDP and no overall association of vaccination with preterm birth; American \nCollege of Obstetricians and Gynecologists was in agreement  with this opinionWork group interpretation of maternal vaccine \nVaccine  Safety Datalink study findings\n9 HDP: hypertensive disorders of pregnancy \n•Long -acting, monoclonal antibody manufactured by Merck\n•Passive immunization\n•Single -dose, manufacturer -filled syringe\n-105 mg/0.7 mL\n-Same dose for all infants regardless of weightInfant RSV Antibody –Clesrovimab\n \n•Clesrovimab  and nirsevimab  recommendations would be the same for use \nin infants younger than 8 months of age born during or entering their first \nRSV season \n-No preferential recommendation for use of clesrovimab  versus nirsevimab\n•Only  nirsevimab1 recommended for children ages 8 through 19 months \nwho are at increased risk of severe RSV disease and entering their second \nRSV season \n-Infants eligible to receive nirsevimab  when entering second RSV season could \nhave received nirsevimab  or clesrovimab  for first RSV season\n-No effectiveness or safety concerns for using clesrovimab  for first RSV season and \nnirsevimab  for second RSV seasonProposed use of clesrovimab versus nirsevimab\n1  Clesrovimab not recommended for this age group because it is not approved by FDA for this indication 11\n•One dose for infants younger than 8 \nmonths of age born during or \nentering their first RSV season \n(administration during October through \nMarch in most of the continental U.S.) if:\n-The mother did not receive RSV vaccine \nduring pregnancy\n-The mother’s RSV vaccination status is \nunknown\n-The infant was born less than 14 days after \nmaternal RSV vaccination\nUse of Nirsevimab for the Prevention of Respiratory Syncytial Virus Disease Among Infants and Young Children: \nRecommendations of the Advisory Committee on Immunization Practices — United States, 2023 | MMWR 12\nProposed recommendations for use \nofRSV antibody immunizations\n(nirsevimab or clesrovimab) in infants \n< 8 months\n•Born to mothers who may not mount an adequate immune response to \nvaccination (e.g., immunocompromising conditions)\n•Born to mothers who have conditions associated with reduced \ntransplacental antibody transfer (e.g., living with HIV infection)\n•Infants who have procedures leading to loss of maternal antibodies (e.g., \ncardiopulmonary bypass, extracorporeal membrane oxygenation [ECMO], \nexchange transfusion) \n•Infants with substantially increased risk for severe RSV disease \n(e.g., hemodynamically significant congenital heart disease, ICU admission \nwith oxygen requirement at discharge) When RSV antibody may be considered for \ninfants born to vaccinated mothers1\nRSV Immunization Guidance for Infants and Young Children | RSV | CDC  | ICU: intensive care unit;  1 For infants aged <8 months during their first RSV season\n\nChoose one product to prevent severe RSV disease in infants\nMost infants will not need both maternal vaccination and an RSV antibody.\nMaternal RSV vaccination\n- Pfizer AbrysvoInfant RSV antibody\n-Nirsevimab\n-Clesrovimab- or -\nInfant RSV antibody and maternal vaccination have \ndifferent administration windows to provide optimal \nprotection to the infant\nOptimal timing for infant RSV administration is shortly before the RSV season\nAdministration should be targeted shortly before the start of their first RSV season and continued during the \nseason for those who have not received a dose\nForinfants born shortly before or during the RSV season , immunize within 1 week of birth, ideally during the birth \nhospitalization\nRSV seasonality differs based on climate\nRSV Immunization Guidance for Infants and Young Children | RSV | CDC\nUse of Nirsevimab for the Prevention of Respiratory Syncytial Virus Disease Among Infants and Young Children: Recommendations  of the Advisory Committee on Immunization Practices — United \nStates, 2023 | MMWR\nIn jurisdictions with differing RSV seasonality (e.g., Alaska, southern Florida, \nPuerto Rico, and other jurisdictions with tropical climates), providers should \nfollow state, local, or territorial guidance on the timing of administration. \nAdminister the correct RSV immunization product\nInfant RSV \nantibody* onlyInfants and Some \nYoung Children\nAbrysvo  (Pfizer) \nonlyDuring Pregnancy\n Older Adults\nDo not administer \nRSV antibody*, Arexvy , \nor mResvia  during \npregnancy.Do not administer \nAbrysvo, Arexvy , or \nmResvia  to infants or \nchildren.Abrysvo  (Pfizer )\n Arexvy  (GSK)\n mResvia  (Moderna )\nDo not administer RSV \nantibody* to older adults.\n*Includes nirsevimab, clesrovimab, and palivizumab.  \nClesrovimab (or nirsevimab) and palivizumab\n•If clesrovimab or nirsevimab is \ngiven to an infant or child… …then do not give palivizumab    \nduring the same RSV season.\nUse of Nirsevimab  for the Prevention of Respiratory Syncytial Virus Disease Among Infants and Young Children: Recommendations of the Advisory C ommittee on Immunization Practices — United \nStates, 2023 | MMWR , AAP Recommendations for the Prevention of RSV Disease in Infants and Children | Red Book Online | American Academy of Pediatr ics\nClesrovimab* \nor nirsevimabPalivizumab\n\nInfant RSV antibody administration\nBeyfortus Prescribing Information (fda.gov)  Enflonsia Prescribing Information.pdf•Route\n-Intramuscular injection\n•Site\n-Vastus lateralis muscle of anterolateral thigh\n-The gluteal muscle should not be used.\n•Coadministration\n-Simultaneous administration with vaccines is \nacceptable. \n\nClesrovimab storage and handling\nStore refrigerated between 2 °C and 8 °C (36°F and 46 °F).\nUse within 48 hours of removing from refrigerator.\n-May be kept at room temperature, between 20 °C and \n25°C (68°F and 77°F), for a maximum of 48 hours\nDo not freeze.\nProtect from light.Do not shake.\nEnflonsia Prescribing Information.pdf\n•If RSV antibody is administered alone:\n-Report suspected adverse events (AEs) to MedWatch\n-www.fda.gov/medwatch\n•If RSV antibody is administered simultaneously with any \nvaccine:\n-Report suspected AEs to Vaccine Adverse Event Reporting System \n(VAERS)\n-vaers.hhs.gov\n-Additional reporting to MedWatch is not necessaryHow to report adverse events after infant RSV \nantibody administration\nRSV Immunization Guidance for Infants and Young Children | RSV | CDC\n\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the \nauthors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention.", "summary": "Work group considerations and  clinical considerations for clesrovimab Maternal and Pediatric RSV Session Coronavirus and Other Respiratory Viruses Division June 25, 2025U.S. Centers for Disease Control and Prevention  •Work group considerations and interpretations of uptake, safety,  effectiveness, and impact studies •Review of clinical considerations -Clesrovimab recommendations compared with nirsevimab -Clesrovimab storage, handling, and administrationOutline 2 •Nirsevimab was effective…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-25-26-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-06-25-26/06-MacNeil-Mat-Peds-RSV-508.pdf", "doc_date": "2025-06-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 22}
{"title": "01 dugan influenza 508", "content": "U.S. Centers for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nInfluenza Session —Introduction\nDr. Vivien Dugan\nInfluenza Division, CDC/NCIRD\nJune 26, 2025\nFlublok (recombinant influenza vaccine) in older children and \nadolescents: immunogenicity and safety\n–Dr. Pedro Folegatti (Sanofi Pasteur)\nEstimates of influenza burden and burden averted through vaccination\n–Dr. Vivien Dugan (CDC/NCIRD)\n2024 -25 influenza season update and seasonal influenza vaccine \nrecommendations for the 2025 -26 U.S. influenza season\n–Dr. Vivien Dugan (CDC/NCIRD)Session Overview\n2", "summary": "U.S. Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. Influenza Session —Introduction Dr. Vivien Dugan Influenza Division, CDC/NCIRD June 26, 2025 Flublok (recombinant influenza vaccine) in older children and …", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-25-26-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-06-25-26/01-dugan-influenza-508.pdf", "doc_date": "2025-06-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 2}
{"title": "02 folegatti influenza 508", "content": "VAP00027\nImmunogenicity and Safety of Quadrivalent Recombinant \nInfluenza Vaccine (RIV4) in Children and Adolescents \nAged 9 to 17 Years and Adults Aged 18 to 49 Years\nFor the Advisory Committee of Immunization Practices (ACIP) Influenza Working Group\nMAT-US-2504669 P v3.0 EXP 28 APR 2026Pedro Folegatti   – Global Clinical Development Director (Presenter)\nThinus Marais – Medical Head: Influenza & COVID, Vaccines North America\nPresenter’s disclosures\nPedro Folegatti , MD DTM&H MSc Dphil \nis a full -time employee of Sanofi and may hold shares \nin the company\nMAT-US-2504669 P v3.0 EXP 28 APR 2026\nRecombinant technology ensures sequence integrity of \nantigens consistent with WHO -identified strains for \nseasonal vaccine formulation\nBEVS, baculovirus expression vector system; CBER, Center  for Biologics Evaluation and Research;  HA, hemagglutinin; MDCK, Madin -Darby Canine Kidney; NIBSC,  National Institute for Biological Standards and \nControl;  rHA, recombinant haemagglutinin; rHA0, recombinant influenza virus hemagglutinins; SF+, spodoptera  frugiperda  (fall armyworm) -positive ; TGA, Therapeutic Goods Administration ; VRBPAC, Vaccines and \nRelated Biological Products Advisory Committee;  WHO, World Health Organization.\nReference : Arunachalam AB, et al. NPJ Vaccines .2021;6:144. Selection of virus strains \nfor vaccine composition\n(WHO, VRBPAC)\nVirus genomeHA proteinWild-type virus\nRIV is produced using the exact genetic \nsequence of the HA protein derived from the WHO \nselected influenza strains; no live virus is used in \nthe manufacturing processIn this novel production platform, \nrHA is expressed in insect cells \nusing BEVSrHA molecules are subsequently extracted  from \nthe infected insect cells and purified  from the \nclarified cell extract before formulationInactive\nvirus\nVirus \ncomponentsPurify and\nformulate\nFormulated\nvaccineDevelop seed virus\n(CBER, NIBSC, TGA)\nEgg-adapted\nseed virus\nCell-adapted \nseed virus Infect egg/cells\nwith flu virusGrow and \nharvest virus\nEmbryonated\nchicken egg\nReplicated\nvirusMDCK cells\n(dog kidney)EGG CELL\nProduce, harvest \nHA proteinPurify and\nformulate\nFormulated\nvaccineHA protein\n(rHA0)HA protein sequenceAdd HA gene to\nBaculovirusInfect SF+cells\nwith Baculovirus\nSF+cells\n(caterpillar)Baculovirus\nwith HA geneRECOMBINANT \nMAT-US-2504669 P v3.0 EXP 28 APR 2026\nSafety and efficacy of RIV in clinical studies and \nreal-world data\nGMT, geometric mean titers; IIV4, quadrivalent inactivated influenza vaccine; RIV3, trivalent recombinant influenza vaccine; RIV4, quadrivalent recombi nant influenza vaccine; SC, seroconversion; US, United States\nReferences: 1. Dunkle  LM, et al. N Engl J Med . 2017;376(25):2427 -36. 2. Dunkle  LM, et al. J Infect Dis. 2017;216(10):1219 -26. 3. Prevention and Control of Influenza with Vaccines: Interim Recommendations of the \nAdvisory Committee on Immunization Practices (ACIP), 2013 . Accessed August 2024. 4. Flublok ® Influenza Vaccine. Product Insert.Clinical data (RIV4) \n•2 Phase III studies \n–Adults 50 years of age and older1 during a season with predominantly antigenically drifted H3N2 strains \n•RIV4 provided  30% (95% CI, 10 to 47)  to 43% (95% CI, 21 to 59) enhanced protection against influenza \ndisease vs IIV4 \n–Adults 18 to 49 years of age2 \n•Non-inferior to the same IIV4 comparator vaccine for 3 of 4 influenza (SC rates and GMTs)\nFirst license and recommendation\n•RIV3 was first licensed in the US in 2013, followed by approval of RIV4 in 2016 for adults ≥18 years of age\n•ACIP recommends use of recombinant influenza vaccination from 20133\nReal -world safety data: \n•~38 million doses of RIV3 and RIV4 distributed cumulatively (Sanofi internal data as of 31 Jan 2024)\n•Established clinical safety profile, well tolerated with no safety concerns4\nMAT-US-2504669 P v3.0 EXP 28 APR 2026\nStudy design\n•Phase III parallel, multi -center , open -label, non -randomized\n•Immuno -bridging study \n•36 centers in Europe (Spain, Poland, Czech Republic) and \nthe United States\n•2022/2023  northern hemisphere influenza\nStudy population:\n•Healthy children & adults; n=1334\n•Aged 9 -49 years\nIntervention:\n•To receive a single dose of:\nRIV4 (9 to 17y) \nn = 667RIV4 (18 to 49y) \nn = 667\nObjectives & endpoints\nPrimary: \n•To demonstrate the non -inferior HAI immune response of RIV4 for 4 \nstrains in participants aged 9 to 17 years vs participants aged 18 to \n49 years\n–HAI titers at D29\n–Seroconversion rates\nSecondary: \n•To describe the safety profile of RIV4 vaccine in all participants and \nby age group \n–Solicited & Unsolicited AEs\n–MAAEs\n–SAEs and AESIs\n•To describe HAI immune responses induced by RIV4\nTrial design (1/2) \nAb, antibody; AE, adverse event; AESI, adverse events of special interest; HAI, hemagglutination inhibiting antibody; MAAEs, medically attended adverse events; NAb, neutralizing antibody; RIV4, recombinant influenza \nvaccine quadrivalent; SAEs, serious adverse events; US, United States. \nMAT-US-2504669 P v3.0 EXP 28 APR 2026\nTrial design (2/2) \nAEs, adverse events; AESIs, adverse events of special interest; CI, confidence interval; D, Day; PC, Phone Call; GMTs, geomet ric mean titers; MAAEs, medically attended adverse event; NI, non -inferiority; RIV4, \nquadrivalent recombinant influenza vaccine; SAEs, serious adverse events; VAC, vaccinationKey exclusion criteria\n•Receipt of any vaccine in the 4 weeks before or after \nenrolment \n–COVID -19 vaccines were allowed within 2 weeks \n(before or after enrolment)\n•Influenza vaccine receipt in the 6 months preceding \nenrolment\nStatistical considerations\n•Overall study power of 80% \n–type II error <20% for the 8 NI tests (GMTs and \nSC on 4 strains)\n•Non-Inferiority Margin\n–Lower bound of the two -sided 95% CI of the ratio \nof GMTs between groups >0.667 for each strain\n–Lower bound of the two -sided 95% CI of \nseroconversion rates ≥ -10% for the 4 strains\nVAC 1 6-months follow -up\nVisit/Contact V01 PC1 V02 PC2\nTime (Day) D01 D09 D29 D181\nUnsolicited\nSystemic\n AEsImmunogenicity\nSafety Solicited\n AEsUnsolicited\nAEs, MAAEsSAEs, AESIs\nRIV4\nBlood samplingGraphical Study design\nMAT-US-2504669 P v3.0 EXP 28 APR 2026\n7 OPTIONS XII Congress, Brisbane, Australia; 29 September – 2 October 2024  Participant disposition\nEnrolment period \n27 October 2022 – 01 May 2023\nN, number of participants; V, visitN planned = 1334\nN enrolled = 1308\n9 to 17 years old\nN planned = 66718 to 49 years old\nN planned = 667\nN at V01 = 648\nN blood sample = 641\nN vaccinated = 641N at V01 = 660\nN blood sample = 658\nN vaccinated = 658\nDiscontinued N = 19\n•Protocol deviation = 6\n•Withdrawal by subject = 2\n•Withdrawal by parent/guardian = 2\n•Lost to follow up = 9Discontinued N = 22\n•Adverse event = 1\n•Protocol deviation = 3\n•Withdrawal by subject = 8\n•Lost to follow up = 10*\nN at V02 = 629\nN blood sample = 626N at V02 = 638\nN blood sample = 634\nN completed the active phase = 629 N completed the active phase = 636*\nTotal completed active phase = 1265\nN at 6 -month \nfollow up = 611N at 6 -month \nfollow up = 613Discontinued N = 2\n•Adverse event = 1\n•Withdrawal by subject = 1\nMAT-US-2504669 P v3.0 EXP 28 APR 2026\n8 OPTIONS XII Congress, Brisbane, Australia; 29 September – 2 October 2024  Baseline Characteristics\nOverall, there were more females  than males (653 females [53.7%] and 562 males [46.3%]) \nand the male/female ratio was 0.86\nThe overall mean age of participants was 23.5 years ( ± 12.5)\n•13 years ( ±2.48) in the 9 -17s and 34 years in the 18 -49s ( ±9.20)\nMost participants (87.0%) were of “Not Hispanic or Latino” ethnicity\nMost participants were White  (77.4%), followed by Black or African American \nparticipants (18.9%)\nMAT-US-2504669 P v3.0 EXP 28 APR 2026\nPrimary objective met\nNon-inferiority of immune response: GMTs at Day 29\n•Non-inferiority of RIV4 in participants 9 to 17 years of age versus participants 18 to 49 years of age was demonstrated for \nGMT ratios of all 4 strains\nGMTs at D29 after vaccination of 9 to 17 years vs 18 to 49 years\nCI, confidence interval; GMT, geometric mean titers; HAI, hemagglutination inhibition;  RIV4, quadrivalent recombinant influenza vaccine1946 \n(1795; 2109)1975\n(1771; 2202)\n405\n(362; 452)1941\n(1779; 2118)982\n(881; 1094) 604\n(531; 687)258\n(233; 285)1593\n(1477; 1717)\n110100100010000\nA/H1N1 A/H3N2 B/Victoria B/YamagataGeometric mean of HAI antibody \ntiter (95% CI)\nInfluenza strain\n9–17 years (D29) 18–49 years (D29)D29 GMT Ratios (95% CI): 9 to 17 years vs 18 to 49 years\n1.98 ( 1.73; 2.27) 3.27 ( 2.76; 3.87) 1.57 ( 1.35; 1.82) 1.22 ( 1.09; 1.37)\nMAT-US-2504669 P v3.0 EXP 28 APR 2026\n•Non-inferiority of RIV4 in participants 9 to 17 years of age versus participants 18 to 49 years of age was demonstrated for \nseroconversion of all 4 strains of influenza\n9 to 17 years minus 18 to 49 years\nAntigen/\nstrainDifference (%) (95% CI) Non-inferiority§\nA/H1N1 1.92 (-2.78; 6.62) Y\nA/H3N2 -0.59 (-4.41; 3.23) Y\nB/Victoria 3.29 (-1.57; 8.14) Y\nB/Yamagata 14.3 (9.17; 19.3) Y\nM, number of participants with available data for the considered endpoint; N, total number of participants included in the st udy; §Non-inferiority for SC rates is demonstrated if the lower limit of \nthe 2-sided 95% CI is ≥ -10% for the 4 strainsImmunogenicity primary objective: Non -inferiority of immune response in terms of seroconversion rates after \nvaccination of 9 to 17 years vs 18 to 49 years\nCI, confidence interval; RIV4, quadrivalent recombinant influenza vaccine; SC, seroconversionPrimary objective met\nNon-inferiority of immune response: Seroconversion\nMAT-US-2504669 P v3.0 EXP 28 APR 2026\nSafety overview\nAR, adverse reactions ; AESI, adverse event of special interest; CI, confidence interval; MAAE, medically attended adverse event; SAE, serious adverse eventDuring the study, 10 participants (0.8%) reported at least 1 SAE and 66 participants (5.1%) \nreported at least 1 MAAE. None of the SAEs and MAAEs were considered as related to the \nvaccine\nNo deaths and no AESIs were reported during the study\nNo substantial differences in safety profile was observed between groups\nMAT-US-2504669 P v3.0 EXP 28 APR 2026\nSolicited reactions within 7 days of vaccinations\n•Most solicited reactions were of Grade 1 or Grade 2 intensity, started within D1 -D4, and resolved (spontaneously) after 1 -3 \ndays\n•Within 28 days of vaccination, 0.9% of participants  in both age groups experienced at least 1 unsolicited injection site AR \nrated as Grade 3\n•Grade 3 solicited injection site reactions consisted predominantly of swelling  in 9 participants of 9 to 17 years group \n(1.5%) and induration  in 5 participants of 18 to 49 years (0.8%)\n•Grade 3 solicited systemic reactions consisted predominantly of headache  and malaise  reported by 16 participants (2.6%, \neach) in 9 to 17 years group. Grade 3 malaise  was reported by 10 participants (1.6%) in 18 to 49 years groups\nAR, adverse reaction; D, day44.3\n6.535.6\n3.129.6\n4.652.9\n4.640.8\n1.436.2\n3.1\n0102030405060\nSolicited reaction Grade 3 solicited reaction Solicited injection site\nreactionGrade 3 injection site\nreactionSolicited systemic reaction Grade 3 systemic reactionParticipants experiencing at \nleast one (%)\n9 to 17 years 18 to 49 yearsSummary of solicited reactions within 7 days after vaccine injection\nMAT-US-2504669 P v3.0 EXP 28 APR 2026\nSolicited injection site reactions after vaccine injection\nAR, adverse reaction\nSummary of solicited injection site reactions after vaccination \n22.22.81.31.81.5\n11.30.61.00.50.5\n0.81.11.50.80.5\n0 5 10 15 20 25Injection site painInjection site erythemaInjection site swellingInjection site indurationInjection site bruising\nPercentage of participants experiencing at least one AR (%)\nGrade 3 Grade 2 Grade 131.21.30.81.90.5\n8.70.91.40.60.2\n0.30.50.50.80.5\n0 5 10 15 20 25 30 35Injection site painInjection site erythemaInjection site swellingInjection site indurationInjection site bruising\nPercentage of participants experiencing at least one AR (%)\nGrade 3 Grade 2 Grade 12.5\n3.1\n3.8\n4.5\n34.31.2\n3.3\n2.7\n2.7\n40.29 to 17 years\n 18 to 49 years\nMAT-US-2504669 P v3.0 EXP 28 APR 2026\nSolicited systemic reactions after vaccine injection\nAR, adverse reaction\n1.00.7\n16.1\n2.88.55.79.13.3\n7.57.88.83.4\n1.02.62.61.50.7\n0 2 4 6 8 10FeverHeadacheMalaiseMyalgiaChills\nPercentage of participants experiencing at least one AR (%)\nGrade 3 Grade 2 Grade 11.19.45.29.43.1\n0.212.19.89.92.5\n0.51.31.60.90.6\n0 2 4 6 8 10 12 14FeverHeadacheMalaiseMyalgiaChills\nPercentage of participants experiencing at least one AR (%)\nGrade 3 Grade 2 Grade 16.2\n20.2\n16.6\n22.8\n1.89 to 17 years\n 18 to 49 years\n1.0\n0.87.4\n19.4\n18.6\nMAT-US-2504669 P v3.0 EXP 28 APR 2026\n13 SAEs reported in the study:\nAll events classified as unrelated by Sponsor and \nInvestigator\n*All participants reporting Psychiatric Disorders SAEs had past medical history of \nmental health disorders prior to enrollment\n^Neurology review attributed event to amphetamine use, sleep deprivation and \nmetabolic disorder \nMAT-US-2504669 P v3.0 EXP 28 APR 2026•7 participants reported  9 SAEs\n•Within 28 days\n•Major Depression  and Intentional \nOverdose*\n•Gastric Cancer Recurrent \n•Suicidal Ideation*\n•Seizure^ \n•Acute Respiratory Failure and \nOverdose\n•During Follow -up\n•Kidney Infection \n•Obstructive Pancreatitis•3 participants reported 4 SAEs\n•Within 28 days\n•Suicidal Ideation and worsening of \nSuicidal Ideation*\n•During Follow -up\n•Suicidal Ideation*\n•Spinal Fracture (post trauma)\n 18-49 years of age 9-17 years of age\nConclusion \n•RIV induced a robust immune response in participants 9 to 17 years and 18 to 49 years\n•These findings are consistent with previous research1-5\n•Non-Inferiority  of HAI immune response induced in those 9 to 17 years of age versus those 18 to 49 years \nof age as assessed by GMTs and SC rates at D29 was met for all 4 influenza strains\n•The safety profile of the RIV4 vaccine was comparable in both age groups\nD, Day; GMT, geometric mean titer; HAI, hemagglutination inhibition; NI, non -inferiority; RIV, recombinant influenza vaccine; SC, seroconversion\nReferences: 1. Hasio  A, et al. N Engl J Med. 2023;389:2245 -2255. 2. Zimmerman RK, et al. Vaccine . 2023;41(35):5134 -5140. 3. Dunkle LM et al. N Engl J Med. 2017;376:2427 -2436.  4. Dunkle  et al. \nPediatrics .2018;141(5):3021. 5. James C King et al. Vaccine . 2009 Nov 5;27(47):6589 -94.\nMAT-US-2504669 P v3.0 EXP 28 APR 2026\nFunding\nFunding\nThis study was funded and \nsponsored by Sanofi\nMAT-US-2504669 P v3.0 EXP 28 APR 2026\nThank you\n©Sanofi 2025. All Rights Reserved.          MAT-US-2504669 P v2.0 EXP 28 APR 2026\nBaseline demographics by age group \n9 to 17 years\n(N=609)18 to 49 years\n(N=606)All\n(N=1215)\nSex, n (%)\nMale 316 (51.9) 246 (40.6) 562 (46.3)\nFemale 293 (48.1) 360 (59.4) 653 (53.7)\nAge, mean (SD), Year 13.0 (2.48) 34.1 (9.20) 23.5 (12.5)\nRacial origin , n (%)\nAmerican Indian or Alaska Native 4 (0.7) 0 4 (0 .3)\nAsian 1 (0.2) 6 (1.0) 7 (0 .6)\nBlack or African American 140 (23.0) 90 (14.9) 230 (18.9)\nNative Hawaiian or Other Pacific Islander 1 (0.2) 2 (0.3) 3 (0.2)\nWhite 447 (73.4) 493 (81.4) 940 (77.4)\nNot Reported 0 2 (0.3) 2 (0.2)\nUnknown 1 (0.2) 1 (0.2) 2 (0.2)\nMultiple 15 (2.5) 12 (2.0) 27 (2.2)\nEthnicity, n (%)\nHispanic or Latino 107 (17.6) 35 (5.8) 142 (11.7)\nNot Hispanic or Latino 494 (81.1) 563 (92.9) 1057 (87.0)\nNot reported 7 (1.1) 8 (1.3) 15 (1.2)\nUnknown 1 (0.2) 0 1 (<0.1)\nn, number of study participants fulfilling the item listed; N, total number of participants included in the study; SD, standa rd deviation\nMAT-US-2504669 P v3.0 EXP 28 APR 2026\nHAI antibody titers\nAb, antibody; CI, confidence interval; D, day; GMT, geometric mean titer; GMTRs, HAI Ab GMT ratios;  HAI, hemagglutination inhibition \n•At baseline, the HAI Ab GMTs were higher in participants 9 to 17 years of age than in participants 18 to 49 years of \nage for the A/H1N1, A/H3N2, B/Victoria lineage, and were similar in both age groups for B/Yamagata lineage strain\n•At D29, the HAI Ab GMTs increased in both age groups and were higher in participants 9 to 17 years of age than in \nparticipants 18 to 49 years of age for all virus strains\nHAI Ab GMTs ( 95% CI ) at baseline HAI Ab GMTs ( 95% CI ) at D29\nAntigen/ strain 9 to 17 years 18 to 49 years 9 to 17 years 18 to 49 years\nA/H1N1 154 (137; 173) 74.9 (65.8; 85.1) 1946 (1795; 2109) 982 (881; 1094)\nA/H3N2 111 (95.4; 128) 29.0 (25.7; 32.8) 1975 (1771; 2202) 604 (531; 687)\nB/Victoria 48.1 (43.0; 53.8) 37.3 (34.0; 40.9) 405 (362; 452) 258 (233; 285)\nB/Yamagata 272 (243; 305) 300 (269; 335) 1941 (1779; 2118) 1593 (1477; 1717)GMTs at baseline and D29 after vaccination of 9 to 17 years vs 18 to 49 years\nMAT-US-2504669 P v3.0 EXP 28 APR 2026\nGeometric mean of HAI antibody titer \n154\n111\n48.127219461975\n4051941\n74.9\n2937.3300982\n604\n2581593\n110100100010000\nA/H1N1 A/H3N2 B/Victoria B/YamagataGeometric mean of HAI antibody titer (95% CI)\nInfluenza strain\nD01 (9 to 17 years) D29 (9 to 17 years) D01 (18 to 49 years) D29 (18 to 49 years)\nCI, confidence interval; D, day; HAI, hemagglutination inhibition \nMAT-US-2504669 P v3.0 EXP 28 APR 2026\nNon-inferiority of immune response: GMTs at Day 29\n•Non-inferiority of RIV4 in participants 9 to 17 years of age versus participants 18 to 49 years of age was demonstrated for \nall 4 ratios of GMTs\n9 to 17 years\n(N=609)18 to 49 years\n(N=606)9 to 17 years / 18 to 49 years\nAntigen/\nstrainM GMT (95% Cl) M GMT (95% Cl) GMT Ratio (95% CI)Non-\ninferiority§\nA/H1N1 609 1946 (1795; 2109) 606 982 (881; 1094) l.98(1.73; \n2.27)Y\nA/H3N2 609 1975 (1771; 2202) 606 604 (531; 687) 3.27(2.76; \n3.87)Y\nB/Victoria 609 405 (362; 452) 606 258 (233; 285) 1.57(1.35; \n1.82)Y\nB/Yamagata 609 1941 (1779; 2118) 606 1593 (1477; 1717) 1.22(1.09; \n1.37)YGMTs at D29 after vaccination of 9 to 17 years vs 18 to 49 years\n; §Non-inferiority is concluded if the lower limit of the two -sided 95% CI of the ratio of GMTs between groups (9 to 17 years/18 to  49 years) is > 0.667 for each strain\nCI, confidence interval; D, day; GMT, geometric mean titers; M, number of participants with available data for the considered endpoint; N, total number of participants; RIV4, quadrivalent recombinant influenza vaccine\nMAT-US-2504669 P v3.0 EXP 28 APR 2026\nIndividual HAI antibody titer ratios\nCI, confidence interval; D, day; GMT, geometric mean titer; GMTRs, HAI Ab GMT ratios;  HAI, hemagglutination inhibition •The post -vaccination GMTRs (D29/D01) were similar in both age groups for A/H1N1, A/H3N2, and B/Victoria lineage \nstrains and were higher in participants 9 to 17 years of age than in participants 18 to 49 years of age for B/Yamagata \nlineage strain\nGMTRs (95% CI)\nAntigen/ strain 9 to 17 years 18 to 49 years\nA/H1N1 12.7 (11.1; 14.5) 13.1 (11.4; 15.0)\nA/H3N2 17.9 (15.7; 20.3) 20.8 (18.4; 23.6)\nB/Victoria 8.41 (7.55; 9.37) 6.91 (6.25; 7.64)\nB/Yamagata 7.13 (6.46; 7.87) 5.31 (4.79; 5.88)\nMAT-US-2504669 P v3.0 EXP 28 APR 2026\nHAI antibody titer ≥40 (1/ dil) and HAI antibody titer ≥10 \n(1/dil)\nCI, confidence interval; D, day; HAI, hemagglutination inhibition•At baseline, the percentages of participants with HAI Ab titer ≥40 (1/ dil) and HAI antibody titer ≥10 (1/ dil) were higher in participants 9 to \n17 years of age than in participants 18 to 49 years of age for the A/H1N1 and A/H3N2, and were similar in both age groups for  B/Victoria \nand B/Yamagata lineage strains\n•At D29, the percentages of participants with HAI Ab titer ≥40 (1/ dil) and HAI antibody titer ≥10 (1/ dil) increased for all 4 virus strains and \nwere high in both age groups\nD01 D29\nPercentage of \nparticipants with \nHAI antibody \ntiter ≥ 40 (95% \nCI)Antigen/ \nstrain9 to 17 years 18 to 49 years 9 to 17 years 18 to 49 years\nA/H1N1 87.2 (84.3; 89.7) 71.8 (68.0; 75.3) 99.7 (98.8; 100) 97.5 (96.0; 98.6)\nA/H3N2 74.7 (71.1; 78.1) 45.0 (41.0; 49.1) 99.0 (97.9; 99.6) 95.0 (93.0; 96.6)\nB/Victoria 61.4 (57.4; 65.3) 59.8 (55.8; 63.8) 95.6 (93.6; 97.1) 97.0 (95.3;98.2)\nB/Yamagata 93.1 (90.8; 95.0) 95.2 (93.2; 96.8) 99.5 (98.6; 99.9) 100 (99.4; 100)\nPercentage of \nparticipants with \nHAI antibody \ntiter ≥ 10 (95% \nCI)A/H1N1 97.0 (95.4; 98.2) 89.8 (87.1; 92.1) 100 (99.4;100) 99.3 (98.3; 99.8)\nA/H3N2 89.2 (86.4; 91.5) 77.7 (74.2; 81.0) 100 (99.4; 100) 99.7 (98.8; 100)\nB/Victoria 92.1 (89.7; 94.1) 91.7 (89.2; 93.8) 99.5 (98.6; 99.9) 99.8 (99.1; 100)\nB/Yamagata 97.9 (96.4; 98.9) 99.5 (98.6;99.9) 100 (99.4; 100) 100 (99.4; 100)\nMAT-US-2504669 P v3.0 EXP 28 APR 2026\nSeroconversion\nSC, seroconversion •The SC rates were similar in both age groups for A/H1N1, A/H3N2, B/Victoria lineage strains and higher in \nparticipants 9 to 17 years of age than in participants 18 to 49 years of age for B/Yamagata lineage strain\nSC (% [95% CI])\nAntigen/ strain 9 to 17 years 18 to 49 years\nA/H1N1 78.3 (74.8; 81.5) 76.4 (72.8; 79.7)\nA/H3N2 86.5 (83.6; 89.1) 87.1 (84.2; 89.7)\nB/Victoria 76.8 (73.3; 80.1) 73.6 (69.8; 77.0)\nB/Yamagata 77.2 (73.6; 80.5) 62.9 (58.9; 66.7)\nMAT-US-2504669 P v3.0 EXP 28 APR 2026\nNeutralizing Ab titers  (SN assay) at D01 and D29 after \nvaccination\nAb, antibody; D, day; GMTR, geometric mean titer ratio; HAI, hemagglutination inhibition; SN, seroneutralization •The post -vaccination SN Ab GMTRs were similar in both age groups for A/H1N1, B/Victoria lineage, and B/Yamagata lineage \nstrains \n•It was higher  in participants 9 to 17 years of age than in participants 18 to 49 years of age for A/H3N2 strain\n614\n200\n65.84667529\n1406\n5453733\n258\n117\n34.23204048\n564\n2402212\n1101001000\nA/H1N1 A/H3N2 B/Victoria B/YamagataGeometric mean\nInfluenza strain\nPre-dose D01 (9 to 17 years) Post-dose D29 (9 to 17 years) Pre-dose D01 (18 to 49 years) Post-dose D29 (18 to 49 years)\nGMTRs (D29/D01) per strain and age group\n12.2\n(9.4; 15.8)15.5\n(11.8; 20.3)7.0\n(5.9; 8.3)4.8\n(4.1; 5.6)8.3\n(6.7; 10.3)7.1\n(5.8; 8.6)8.0\n(6.5; 9.8)6.8\n(5.5; 8.5)\nMAT-US-2504669 P v3.0 EXP 28 APR 2026\nSummary of geometric mean of HAI antibody titer at \nbaseline (D01) and D29 by age subgroup\nAb, antibody; CI, confidence interval; D, day; GM, geometric mean; HAI, hemagglutination inhibition; M, number of participants with available data for the considered endpoi nt; V, visit 9 to 11 years \n(N=186)12 to 17 years \n(N=423)18 to 34 years \n(N=303)35 to 49 years \n(N-303)\nStrain Time Point M GM (95% CI) M GM (95% CI) M GM (95% CI) M GM (95% CI)\nA/H1N1 V01 (D01) 186 139 (112; 173) 423 160 (139; 184) 303 102 (85.2; 122) 303 55.0 (46.0; 65.7)\nV02 (D29) 186 2101 (1786; 2472) 423 1881 (1717; 2062) 303 1499 (1313; 1711) 303 643 (549; 753)\nA/H3N2 V01 (D01) 186 152 (117; 198) 423 96.1 (80.6; 115) 303 27.7 (23.2; 33.0) 303 30.4 (25.6; 36.0)\nV02 (D29) 186 2550 (2129; 3055) 423 1765 (1543; 2019) 303 644 (536; 775) 303 567 (473; 679)\nB/Victoria V01 (D01) 186 36.3 (30.4; 43.4) 423 54.4 (47.4; 62.6) 303 36.5 (32.0; 41.7) 303 38.1 (33.6; 43.3)\nV02 (D29) 186 308 (248; 383) 423 456 (402; 517) 303 270 (232; 315) 303 247 (216; 281)\nB/Yamagata V01 (D01) 186 169 (136; 210) 423 336 (296; 381) 303 435 (377; 501) 303 207 (178; 242)\nV02 (D29) 186 1339 (1101; 1627) 423 2286 (2094; 2496) 303 2211 (2026; 2414) 303 1147 (1026; 1282)Table 5: Summary of geometric mean of HAI antibody titer at baseline (D01) and D29 by age subgroup\nMAT-US-2504669 P v3.0 EXP 28 APR 2026\nSummary of geometric mean of HAI antibody titer at \nbaseline (D01) and D29 by priming status\nCI, confidence interval; D, day; GM, geometric mean; HAI, hemagglutination inhibition; M, number of participants with available data for the considered endpoi nt; V, visit 9 to 17 years 18 to 49 years\nPreviously unvaccinated* \n(N-425)Previously vaccinated† \n(N=180)Previously unvaccinated* \n(N=409)Previously vaccinated†\n(N=193)\nStrain Time Point M GM (95% CI) M GM (95% CI) M GM (95% CI) M GM (95% CI)\nA/H1N1 V01 (D01) 425 123 (107; 142) 180 255 (208; 313) 409 50.1 (43.2; 58.1) 193 168 (137; 207)\nV02 (D29) 425 2276 (2072; 2501) 180 1351 (1169; 1561) 409 1152 (1004; 1322) 193 698 (591; 824)\nA/H3N2 V01 (D01) 425 103 (85.5; 123) 180 135 (105; 173) 409 24.7 (21.3; 28.5) 193 39.9 (31.9; 49.7)\nV02 (D29) 425 2054 (1804; 2339) 180 1838 (1502; 2250) 409 648 (553; 759) 193 518 (414; 647)\nB/Victoria V01 (D01) 425 37.7 (32.9; 43.1) 180 86.7 (72.8; 103) 409 29.8 (26.7; 33.1) 193 59.0 (50.6; 68.7)\nV02 (D29) 425 399 (348; 457) 180 422 (348; 512) 409 270 (238; 306) 193 236 (199; 280)\nB/Yamagata V01 (D01) 425 215 (187; 247) 180 474 (401; 560) 409 240 (210; 275) 193 478 (406; 564)\nV02 (D29) 425 1995 (1785; 2229) 180 1803 (1575; 2064) 409 1784 (1629; 1955) 193 1266 (1113; 1441)Table 17: Summary of geometric mean of HAI antibody titer at baseline (D01) and D29 by priming status\nMAT-US-2504669 P v3.0 EXP 28 APR 2026\nSummary of geometric mean of HAI antibody titer at \nbaseline (D01) and D29 by baseline seropositivity\nCi, confidence interval; D, day; GM, geometric mean; HAI, hemagglutination inhibition; M, number of participants with available data for the considered endpoi nt; V, visit 9 to 17 years 18 to 49 years\nBaseline seropositive for Baseline seronegative for Baseline seropositive for Baseline seronegative for\nStrain Time Point M GM (95% CI) M GM (95% CI) M GM (95% CI) M GM (95% CI)\nA/H1N1 V01 (D01) 591 170 (153; 190) 18 5.00 (NC; NC) 544 102 (90.6; 115) 62 5.00 (NC; NC)\nV02 (D29) 591 1989 (1839; 2152) 18 941 (391; 2265) 544 1181 (1071; 1303) 62 193 (123; 305)\nA/H3N2 V01 (D01) 543 161 (141; 184) 66 5.00 (NC; NC) 471 48.0 (42.4; 54.4) 135 5.00 (NC; NC)\nV02 (D29) 543 2518 (2289; 2770) 66 268 (184; 390) 471 915 (809; 1036) 135 142 (109; 186)\nB/Victoria V01 (D01) 561 58.4 (52.5; 65.0) 48 5.00 (NC; NC) 555 44.7 (41.1; 48.6) 50 5.00 (NC; NC)\nV02 (D29) 561 471 (424; 524) 48 68.3 (45.1; 103) 555 280 (253; 310) 50 101 (69.0; 149)\nB/Yamagata V01 (D01) 596 297 (268; 330) 13 5.00 (NC; NC) 603 306 (275; 341) 3 5.00 (NC; NC)\nV02 (D29) 596 2076 (1918; 2248) 13 89.0 (37.3; 212) 603 1596 (1480; 1722) 3 1016 (NC; NC)Table 21: Summary of geometric mean of HAI antibody titer at baseline (D01) and D29 by baseline seropositivity\nMAT-US-2504669 P v3.0 EXP 28 APR 2026\nSafety overview\n•During the study, 10 participants (0.8%) reported at least 1 SAE and 66 participants (5.1%) reported at least 1 MAAE. \nNone of the SAEs and MAAEs were considered as related to the vaccine\n•No deaths and no AESIs were reported during the study\nSafety overview after vaccine injection\n9 to 17 years\n(N=641)18 to 49 years\n(N=658)All\n(N=1299)\nPeriod/Participants experiencing \nat least one:n/M % (95% Cl) n/M % (95% Cl) n/M % (95% Cl)\nWithin 28 days after vaccine injection\nUnsolicited AR 30/641 4.7 (3.2; 6.6) 26/658 4.0 (2.6; 5.7) 56/1299 4.3 (3.3; 5.6)\nAE leading to discontinuation 0/641 0 (0; 0.6) 2/658 0.3 (0; 1.1) 2/1299 0.2 (0; 0.6)\nDuring the study\nSAE 3/641 0.5 (0.1; 1.4) 7/658 1.1 (0.4; 2.2) 10/1299 0.8 (0.4; 1.4)\nDeath 0/641 0 (0; 0.6) 0/658 0 (0; 0.6) 0/1299 0 (0; 0.3)\nAESI 0/641 0 (0; 0.6) 0/658 0 (0; 0.6) 0/1299 0 (0; 0.3)\nMAAE 29/641 4.5 (3.1; 6.4) 37/658 5.6 (4.0; 7.7) 66/1299 5.1 (4.0; 6.4)\nM, number of participants with available data for the relevant endpoint; n, number of participants experiencing the endpoint listed in the first column; N, total number of participants included in \nthe study \nAR, adverse reactions ; AESI, adverse event of special interest; CI, confidence interval; MAAE, medically attended adverse event; SAE, serious adverse event\nMAT-US-2504669 P v3.0 EXP 28 APR 2026", "summary": "VAP00027 Immunogenicity and Safety of Quadrivalent Recombinant  Influenza Vaccine (RIV4) in Children and Adolescents  Aged 9 to 17 Years and Adults Aged 18 to 49 Years For the Advisory Committee of Immunization Practices (ACIP) Influenza Working Group MAT-US-2504669 P v3.0 EXP 28 APR 2026Pedro Folegatti   – Global Clinical Development Director (Presenter) Thinus Marais – Medical Head: Influenza & COVID, Vaccines North America Presenter’s disclosures Pedro Folegatti , MD DTM&H MSc Dphil  is a…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-25-26-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-06-25-26/02-folegatti-influenza-508.pdf", "doc_date": "2025-06-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 30}
{"title": "03 dugan influenza 508", "content": "Severity, Disease Burden, and Prevented Burden for \nthe 2024 -2025 Influenza Season\nInfluenza Division, CDC\n\n2024 -2025 Influenza Season News\n\nInfluenza Severity Assessment by Season and  by Age Group\nSeverity Classification by Age Group\nInfluenza Season* 0-17 years 18-64 years ≥65 years All Ages\n2009- 2010 Very High Moderate Low Moderate\n2010- 2011 Moderate Moderate Moderate Moderate\n2011- 2012 Low Low Low Low\n2012- 2013 Moderate Moderate High Moderate\n2013- 2014 Moderate Moderate Moderate Moderate\n2014-2015 Moderate Moderate High High\n2015- 2016 Low Moderate Low Moderate\n2016- 2017 Moderate Moderate Moderate Moderate\n2017- 2018 High High High High\n2018- 2019 Moderate Moderate Moderate Moderate\n2019- 2020 High High Moderate Moderate\n2021- 2022 Low Low Low Low\n2022- 2023 High Moderate Moderate Moderate\n2023- 2024 Moderate Moderate Moderate Moderate\n2024-2025 High High High High\n*Severity assessment was not completed for 2020 -2021 season because of minimal influenza activity\nInfluenza Disease Burden Estimation\n•Influenza is not a notifiable , reportable disease in the U.S. \n-Except for pediatric deaths\n•Sentinel surveillance systems in healthcare settings cannot capture all \ninfluenza virus infections\n•Not everyone who is ill seeks medical care\n•Not everyone who seek medical care will be tested for influenza \n•Even if someone with influenza seeks care and is tested, depending on where \nin the course of an illness and type of specimen collected, they may test negative\n•Influenza symptoms are non -specific and individuals could be misdiagnosed \nwith having a different respiratory illness especially when not testedWhy it is necessary to estimate influenza disease burden\nhttps://www.cdc.gov/flu -burden/php/about/why -cdc-estimates.html\n•Disease burden is estimated by \nclinical disease severity\n•Calculated using five age groups:\n-0-4 years \n-5-17 years \n-18-49 years\n-50-64 years\n-65+ yearsU.S. Annual Influenza Burden Estimates\nDeaths\nHospitalizations\nMedically attended \nillnesses\nCommunity symptomatic \nillnesses\nHospitalizations\n(Crude hospitalization rate) x (adjustment for \ntesting practices) x population1\nSymptomatic community illness\n(Hospitalizations) x ( case:hospitalization  ratio)3Outpatient medical visits:\n(Symptomatic community illness) x \n(probability of seeking medical care when ill)4Deaths\n(Hospitalizations) x \n(death:hospitalization  ratio)2Data Source\nCause of death from death \ncertificate, risk of death when hospitalized, and location of death (in vs. out of hospital (ref 1)\nRoutine sentinel surveillance for patients hospitalized with \nlaboratory -confirmed \ninfluenza and data from a \nsurvey of influenza testing \npractices at sentinel hospitals \n(ref 1)\nTelephone survey of healthcare -seeking behavior \nduring influenza -like illness \n(ref 3)\nField investigations of influenza (ref 2)Burden level\nMethodologyStep \n#Legend\n1: R eed, et al., PLoS One. 2015\n2: R eed , et al., EID. 2009\n3: Biggerstaff, et al., AJPH . 2012\nPreliminary Influenza Disease Burden, 2024- 2025 by Age Group\nAge GroupSymptomatic Illnesses \n(95% Uncertainty \nInterval)Medically Attended Illnesses\n(95% Uncertainty Interval)Hospitalizations\n(95% Uncertainty \nInterval)\n0-4 years3,600,000\n(2,900,000, 5,800,000)2,400,000\n(1,800,000, 4,000,000)25,000\n(20,000, 40,000)\n5-17 years11,000,000\n(8,600,000, 24,000,000)5,800,000\n(4,100,000, 12,000,000)31,000\n(24,000, 65,000)\n18-49 years22,000,000\n(16,000,000, 38,000,000)8,100,000\n(5,300,000, 14,000,000)120,000\n(91,000, 210,000)\n50-64 years14,000,000\n(10,000,000, 31,000,000)6,000,000\n(3,700,000, 13,000,000)150,000\n(110,000, 320,000)\n≥65 years4,900,000\n(3,400,000, 11,000,000)2,700,000\n(1,700,000, 6,200,000)440,000\n(310,000, 990,000)\nTotal56,000,000\n(47,000,000, 83,000,000)25,000,000\n(20,000,000, 38,000,000)770,000\n(620,000, 1,400,000)\nInfluenza Disease Burden Varied by Season \n23,000,000\n9,400,00034,000,00030,000,000 30,000,000\n24,000,00029,000,00041,000,000\n29,000,00034,000,000\n11,000,00031,000,00040,000,00056,000,000 11,000,000\n4,400,00016,000,000\n13,000,000 14,000,000\n11,000,00014,000,00019,000,000\n14,000,00015,000,000\n5,100,00014,000,00018,000,00025,000,000\n2010-11 2011-12 2012-13 2013-14 2014-15 2015-16 2016-17 2017-18 2018-19 2019-20 2021-22 2022-23 2023-24 2024-25Number of Symptomatic Illnesses, Medical Visits, and \nHospitalizations\nSeasonSymptomatic Illnesses Medical Visits Hospitalizations\n140,000580,000\n350,000590,000\n280,000500,000710,000\n400,000380,000\n120,000370,000470,000770,000\n310,000\n* * *\n*Preliminary Estimates\nInfluenza Vaccine Prevented Influenza \nDisease Burden Estimation\nInfluenza Vaccine Prevented Disease Burden Components\n56 million \nillnesses\n770,000 hospitalizations25 million medical visits\n35–71%\n(Varies by age group)38–56%\n(Varies by age \ngroup \nand flu type)Disease Burden Vaccine Coverage Vaccine Effectiveness\nOutpatient\nInpatient\n39–62%\n(Varies by age \ngroup \nand flu type)\nData Sources: Vaccine Coverage: NIS-FLU, BRFSS ; Outpatient VE estimates: VE Network , NVSN , VISION Network ; \nInpatient VE estimates: NVSN, VISION Network, IVY\nhttps://www.cdc.gov/flu -burden/php/about -burden- prevented/index.html  \nInfluenza Prevented Disease Burden Model\nEstimated \nMedical VisitsEstimated \nHospitalizationsEstimated \nDeaths\nObserved burden \noutcomes with \nvaccinationExpected burden \noutcomes without \nvaccinationBurden outcomes \nprevented by \nvaccination\nUse vaccine coverage \n(VC) and vaccine \neffectiveness (VE) \nestimate risk to \nsusceptible personsApply risk of burden  \noutcomes among \nsusceptible persons to \nhypothetical susceptible \npopulation without \nvaccinationMonte Carlo \nsimulation \nmethodology to \nestimate uncertaintyDisease \nburden model\nPrevented \ndisease burden \nmodel\nCalculated monthly \nby age groupEstimated \nInfectionsAdjusted \nHospitalization \nRates\n∝\n1-VE, 1 -VC\nPreliminary Influenza Disease Burden Prevented by Vaccination, 2024-\n2025 by Age Group\nAge Group Symptomatic Illnesses Medically Attended Illnesses Hospitalizations\n0-4 years1,200,000\n(910,000, 2,000,000)810,000\n(600,000, 1,300,000)9,700\n(7,300, 16,000)\n5-17 years2,200,000\n(1,600,000, 4,800,000)1,200,000\n(840,000, 2,500,000)7,700\n(5,600, 17,000)\n18-49 years3,800,000\n(2,700,000, 6,400,000)1,400,000\n(1,000,000, 3,000,000)18,000\n(13,000, 31,000)\n50-64 years3,300,000\n(2,300,000, 7,300,000)1,400,000\n(1,000,000, 3,000,000)32,000\n(22,000, 63,000)\n≥65 years1,600,000\n(1,100,000, 3,500,000)900,000\n(600,000, 2,000,000)170,000\n(120,000, 380,000)\nTotal12,000,000\n(10,000,000, 18,000,000)5,700,000\n(4,800,000, 8,400,000)240,000\n(180,000, 460,000)\nInfluenza Disease and Prevented Burden 2011 -2024†Number of Illnesses, Hospitalizations, and Deaths140,000580,000\n350,000590,000\n280,000500,000710,000\n400,000 380,000\n120,000370,000470,000770,000\n45,000119,000\n120,000112,000\n73,00065,00083,000\n36,000 98,000\n26,00071,000120,000240,000Hospitalizations Prevented Hospitalizations\n9,400,00034,000,00030,000,000 30,000,00024,000,00029,000,00041,000,000\n29,000,00034,000,000\n11,000,00031,000,00040,000,00056,000,000\n2,300,0008,100,0008,000,0003,200,000\n5,600,0004,900,0006,000,000\n2,800,0006,700,000\n1,900,0005,500,0009,800,00012,500,000\n2011-12 2012-13 2013-14 2014-15 2015-16 2016-17 2017-18 2018-19 2019-20 2021-22 2022-23 2023-24 2024-25Symptomatic Illnesses Prevented Sympotmatic Illnesses11,000,000\n4,400,00016,000,00013,000,000 14,000,00011,000,00014,000,00019,000,00014,000,000 15,000,000\n5,100,00014,000,00018,000,00025,000,000 3,100,000\n1,100,0004,000,000\n3,700,000 1,700,0002,700,0002,500,0003,100,000\n1,500,0003,300,000\n990,0002,700,0004,800,0005,700,000Medical Visits Prevented Medical Visits\n*\n*Preliminary Estimates; †https://www.cdc.gov/flu -burden/php/data -vis-vac/past -burden -prevented -est.html \n * *\n•Influenza causes significant impacts on healthcare settings and substantial \ndisease burden on the population\n•2024- 2025 season was classified as high severity for all age ages and by age \ngroup and is the first high severity season since 2017- 2018\n•Estimated influenza disease burden was the highest the U.S. has seen in the \nlast decade\n•Influenza vaccine prevented an estimated 240,000 hospitalizations, most in \nadults aged 65 years and older, and likely prevented the season from being even more severeConclusions\nFor more information, contact CDC\n1-800- CDC- INFO (232 -4636)\nTTY:  1 -888- 232- 6348    cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the U.S. Centers for Disease Control and Prevention.", "summary": "Severity, Disease Burden, and Prevented Burden for  the 2024 -2025 Influenza Season Influenza Division, CDC  2024 -2025 Influenza Season News  Influenza Severity Assessment by Season and  by Age Group Severity Classification by Age Group Influenza Season* 0-17 years 18-64 years ≥65 years All Ages 2009- 2010 Very High Moderate Low Moderate 2010- 2011 Moderate Moderate Moderate Moderate 2011- 2012 Low Low Low Low 2012- 2013 Moderate Moderate High Moderate 2013- 2014 Moderate Moderate Moderate…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-25-26-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-06-25-26/03-dugan-influenza-508.pdf", "doc_date": "2025-06-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 17}
{"title": "04 dugan influenza 508", "content": "U.S. Centers for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\n2024 -25 Influenza Season Update and Seasonal Influenza \nVaccine Recommendations for the 2025 -26 U.S. Influenza \nSeason\nDr. Vivien Dugan\nInfluenza Division, CDC/NCIRD\nJune 26, 2025\n2024 -25 influenza season summary\nProposed updates to the seasonal influenza vaccine recommendations \nfor the 2025 -26 influenza season including the following recent FDA \napprovals:\n–Influenza vaccine composition for the 2025 -26 season\n–FluMist (live attenuated influenza vaccine, trivalent) for self -or caregiver \nadministration \n–Change in age indication for Flublok (recombinant influenza vaccine, trivalent) \nfrom ≥18 years to ≥9 yearsOverview\n2\n2024 -25 Influenza Season\nHigh severity season overall and for all age groups\n–First high severity season since 2017 -2018\nHighest cumulative influenza -associated hospitalization rate since \n2010 -2011\n–October 1, 2024 through April 30, 2025: 128.1 per 100,000\n–Cumulative rate was 102.9 per 100,000 for the severe 2017 -18 season\nAs of June 7, 246 influenza -associated pediatric deaths have been \nreported this season2024 -25 U.S. Influenza Season\n4Weekly US Influenza Surveillance Report: Key Updates for Week 20, ending May 17, 2025 | FluView | CDC\nWeekly US Influenza Surveillance Report: Key Updates for Week 23, ending June 7, 2025 | FluView | CDC\nInfluenza -Associated Hospitalizations, FluSurv -NET, 2024 -\n2025 Season\nLab -confirmed influenza -associated hospitalizations in \nselect counties in 14 states\nApprox. 9% of  U.S. population\nAs of May 17, cumulative rate of 128.1 per 100,00\n–Was 102.9 for 2017 -18\nApprox 16% of hospitalized patients required ICU \nadmission and 6% required invasive mechanical ventilation  \nWeekly US Influenza Surveillance Report: Key Updates for Week 20, ending May 17, 2025 | FluView | CDC5103.4\n39.8 51.9149.7403.4\n0100200300400500\n0-4 5-17 18-49 50-64 ≥65Rate (per 100,000 population)\nAge groupCumulative rate of laboratory -confirmed influenza \nhospitalizations by age - FluSurv -NET, 2024 -25 season102.9\n020406080100120140Rate per 100,000 population\nInfluenza SeasonCumulative rate of laboratory -confirmed influenza \nhospitalizations by season –– FluSurv- NET,  2010- 11 –  2024 -25 \nseasons\n128.1\nInfluenza- Associated Pediatric Mortality, \n2024 -2025 Season*\nDeath in a person <18 yrs of age\n–with clinically compatible illness \n–and influenza positive laboratory test\n–and no period of complete recovery \nbetween illness and death\nNationally notifiable since 2004\n246 deaths reported*\nAll age groups affected\n•0-5 months:   7%\n•6-23 months: 13%\n•2-4 years: 18%\n•5-11 years: 37%\n•12-17 years: 26%\n* Through June 7, 2025 https://gis.cdc.gov/GRASP/Fluview/PedFluDeath.html 6\nInfluenza- Associated Pediatric Mortality, \n2024 -2025 Season*\nAmong 246 influenza -associated pediatric deaths reported thus far \nfor 2024-25*,\n–42% had no known high risk underlying medical condition\n–40% had a bacterial co -infection of a sterile site\n–89% of those eligible for influenza vaccination were not fully vaccinated\n•Compared with 82% for the 2023 -24 season\nHighest number of pediatric deaths reported in any non -pandemic \ninfluenza season since condition became reportable in 2004\n* Through June 7, 2025 https://gis.cdc.gov/GRASP/Fluview/PedFluDeath.html 7\n2025 -26 Seasonal Influenza Vaccine \nRecommendations\n8\nAnnual influenza vaccination remains recommended for those aged    \n≥6 months who do not have contraindications \nAs previously, \n–No preferential recommendations are made with the exception that high- dose \ninactivated, recombinant, and adjuvanted inactivated influenza vaccines are \npreferentially recommended for persons aged ≥65 years when available\n–Recipients should receive an age -appropriate influenza vaccine (one approved for \ntheir age), with the exception that solid organ transplant recipients aged ≥18 years who are taking immunosuppressive medications regimens may receive either high- dose or adjuvanted inactivated vaccines (without preference over \nother appropriate influenza vaccines)\nRecommendations concerning timing, vaccine selection, and \ncontraindications and precautions remain the same as previouslySeasonal Influenza Vaccine Recommendations, 2025 -26\n9 MMWR 2024;73(RR- 5):1-25\nThe 2025 -26 recommendations include three updates, all of which \nreflect recent FDA approvals:\n–Influenza vaccine composition for the 2025 -26 season\n–FluMist (live attenuated influenza vaccine, trivalent; LAIV3) for self - or caregiver \nadministration \n–Change in age indication for Flublok (recombinant influenza vaccine, trivalent; \nRIV3) from ≥18 years to ≥9 yearsRecommendations for 2025 -26: Updates\n10\nAll influenza vaccines marketed in the United States for the 2025 -26 \nseason will be trivalent\nU.S. influenza vaccine composition for 2025 -26 includes an update to \nthe influenza A(H3N2) component:\n–AnA/Victoria/4897/2022 (H1N1)pdm09 -like virus for egg -based vaccines \nor an A/Wisconsin/67/2022 (H1N1)pdm09 -like virus for cell and recombinant \nvaccines;\n–An A/Croatia/Y10136RV/2023 (H3N2)- like virus for egg -based vaccines \nor an A/District of Columbia/27/2023 (H3N2) -like virus for cell and recombinant \nvaccines;\n–A B/Austria/1359417/2021 (B/Victoria lineage)- like virusU.S. Influenza Vaccine Composition for the 2025 -26 \nInfluenza Season\nInfluenza Vaccine Composition for the 2025 -2026 U.S. Influenza Season | FDA 11\nApproved by FDA in September 20241; presented to ACIP in April 2025\nAnticipated to be available for the 2025 -26 influenza season\nConsumers will be able to order FluMist  for delivery for eligible \nrecipients\n–Screening for eligibility performed by central pharmacy, based on ACIP criteria\n–Approved for self- administration for persons aged ≥18 years, or by a caregiver \naged ≥18 years for recipients aged 2 through 17 years\nLAIV3 will continue to be available for administration by healthcare \nproviders as previously\nNo changes made to recommendations regarding appropriate populations, contraindications, or precautionsFluMist (LAIV3) for Self-  or Caregiver Administration\n12 1.https://www.fda.gov/vaccines -blood -biologics/vaccines/flumist\nApproved by FDA in March 20251\nPreviously approved for ≥18 years; new age indication is ≥9 years\nInformation has been updated in the Table of available U.S. influenza \nvaccines for 2025 -26Approval of Flublok (RIV3) for Persons Aged 9 through 17 \nYears\n1.https://www.fda.gov/vaccines -blood -biologics/vaccines/flublok 13\nFor more information, contact CDC\n1-800- CDC- INFO (232 -4636)\nTTY:  1 -888 -232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention.\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\n14", "summary": "U.S. Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. 2024 -25 Influenza Season Update and Seasonal Influenza  Vaccine Recommendations for the 2025 -26 U.S. Influenza  Season Dr. Vivien Dugan Influenza Division,…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-25-26-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-06-25-26/04-dugan-influenza-508.pdf", "doc_date": "2025-06-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 14}
{"title": "05 influenza redwood 508", "content": "ACIP 2025\nBusinessThimerosal as a Vaccine Preservative\nPrepared for the \nAdvisory Committee for \nImmunization PracticesLyn Redwood RN, MSN, FP (Retired)\n\n2The Food and Drug Administration \nModernization Act of 1997\n•Compiled list of drugs and foods that contained intentionally introduced \nmercury compounds\n•Provided quantitative and qualitative analysis of mercury compounds\n•Report included 219 products which included 11 biologics and immunoglobulin \ntherapies\nRef: U.S. Congress. (1997, November 21). Food and Drug Administration Modernization Act of 1997, Pub. L. No. 105 -115, 111 Stat. 2296.\n\n31999 Joint Statement by US Public Health Service \n(PHS) and American Academy of Pediatrics (AAP)\nThimerosal in Vaccines: A Joint Statement of the American Academy of Pediatrics and the Public Health \nService. MMWR Weekly. July 09, 1999 / 48(26);563 -565.•On July 9th , 1999, a joint statement issued by PHS and AAP called for the immediate \nreduction and elimination of the mercury based preservative thimerosal from infant \nvaccines based on the findings that infants and children who received vaccines \npreserved with thimerosal could be exposed to mercury in excess of federal safety \nguidelines.\n•“because any potential risk is of concern, the Public Health Service (PHS), the \nAmerican Academy of Pediatrics (AAP), and vaccine manufacturers agree that \nthimerosal -containing vaccines should be removed as soon as possible.”\n\n4 Institute of Medicine \nImmunization Safety Review of Thimerosal Containing Vaccines \nand Neurodevelopmental Disorders (October 2001)\n•The committee “supported prior decisions made by the ACIP and AAP to call for the removal of \nthimerosal from vaccines that are part of the recommended childhood immunization schedule.” \nBut they noted that “vaccines that are not part of the recommended childhood immunization \nschedule still contain thimerosal as a preservative and may be given to some children” and a \nlingering concern that there remains “on the shelf” an unknown quantity of thimerosal -containing \nHib, hepatitis B, and DTaP vaccines.\n•Recommended: “the use of thimerosal free DTaP , HiB and Hepatitis B vaccines despite the fact that \nthere might be remaining supplies available” and “full consideration be given by appropriate \nprofessional societies and government agencies to removing thimerosal from vaccines \nadministered to infants, children or pregnant women in the united States. ”\nInstitute of Medicine (US) Immunization Safety Review Committee; Stratton K, Gable A, McCormick MC, editors. Immunization Saf ety Review: Thimerosal -\nContaining Vaccines and Neurodevelopmental Disorders. Washington (DC): National Academies Press (US); 2001. Immunization Safe ty Review, Thimerosal -\nContaining Vaccines and Neurodevelopmental Disorders. Available from: https://www.ncbi.nlm.nih.gov/books/NBK223724/\n\n5Safety Studies\nPrior to Marketing Thimerosal as Vaccine Preservative\n(1) Ball LK, Ball R, Pratt RD. An assessment of thimerosal use in childhood vaccines  Pediatrics. 2001;(107)5:1147 -1153.\n(2) Powell HM, Jamieson WA. Merthiolate as a germicide.  Am J. Hyg. 1931;(13):296 -310.\n(3) Department of Health and Human Services. 21 Code of Federal Regulations: 601.25. 1985•In 1997, FDA Modernization Act prompted assessment of thimerosal use in vaccines. \n•FDA was unable to find any clinical studies formally evaluating the use of thimerosal \nbefore its initial marketing in 1930’s. (1)\n•Single study published in 1931 where thimerosal administered to individuals suffering \nfrom meningitis. (2)\n-Not designed to specifically examine toxicity and no clinical assessments or laboratory \nstudies reported.\n•FDA grandfathered in the use of thimerosal and did not require the typical animal safety \ndata for finished biological products, including active and inactive ingredients. (3)\n\n6 Thimerosal use in vaccines\nRef:  1. Ball LK, Ball R, Pratt RD. An assessment of thimerosal use in childhood vaccines  Pediatrics. 2001;(107)5:1147 -1153. \n         2. Powell HM, Jamieson WA. Merthiolate as a germicide.  Am J. Hyg. 1931;(13):296 -310. \n         3. Department of Health and Human Services. 21 Code of Federal Regulations: 601.25. 1985 •Thimerosal was first introduced as a preservative in vaccines in the 1930’s after being \ndeveloped and patented in 1927 and subsequently marketed by Eli Lilly under the trade \nname “Merthiolate” in 1928.\n•After a deadly incident of bacterial contamination of vaccines in Australia where 12 \nchildren died from staphylococcal -contaminated diphtheria vaccine, the FDA began \nenforcing safety standards which led to regulations requiring that all multidose vaccines \ncontain a preservative to prevent contamination.\n•Thimerosal was used during the manufacturing process and in multi -dose vials to \nprevent bacterial and fungal contamination. By the 1930’s thimerosal became widely \nused as a preservative in vaccines and other medical products.\n\n7 Thimerosal Not Generally Recognized \nas Safe and Effective (GRASE) in OTC Drugs\nRef: Federal Register, Department of Health and Human Services, Food and Drug Administration. Mercury -Containing Drug Products for Topical \nAntimicrobial Over -the-Counter Human Use; Establishment of a Monograph. (January 5, 1982);47(2):436 -442. 47 FR 436 [Docket No. 75N -0183(1) \nFederal Register, Department of Health and Human Services, Food and Drug Administration. Status of Certain Additional Over -the-Counter Drug \nCategory II and III Active Ingredients. (April 22, 1998);63(77):19799 -19802. 21 CFR Part 310 [Docket No. 75N -183F, 75N -183D, and  80N-0280.    •In 1975, FDA convened panel of experts to evaluate the use of mercury -containing over -the-counter (OTC). The panel \nfound evidence that thimerosal was “35.3 times more toxic for embryonic chick heart tissue than for Staphylococcus \naureus” and “was no better than water in protecting mice from potential fatal streptococcal infections.” \n•The FDA issued a report of the panel’s findings in the Federal Register in 1982 which concluded that “thimerosal was \nnot safe for OTC topical use because of its potential for cell damage if applied to broken skin and its allergy potential, \nnot effective “because bacteriostatic action could be reversed.”  \n• In response to the expert panels report, the FDA published final rules in the Federal Register in 1998  that concluded  \nthe use of thimerosal in over -the-counter products is not “generally recognized as safe or effective.” (GRASE)\n\n8\nEvidence of Thimerosal \nIneffectiveness as a Preservative\nStetler HC, Garbe PL, Dwyer DM, Facklam RR, Orenstein WA, West GR, Dudley KJ, Bloch AB. Outbreaks of group A streptococcal ab scesses following diphtheria -\ntetanus toxoid -pertussis vaccination. Pediatrics. 1985 Feb;75(2):299 -303. PMID: 3881728. \nSmith S. Safety fears cut vaccine for flu. Priority urged for the aged, frail. Boston Globe . (October 6, 2004). \nhttp://www.boston.com/news/globe/health_science/articles/2004/10/06/safety_fears_cut_vaccine_for_flu?mode=PF•In 1982, clusters of disease from Group A streptococcus infections were traced back to multi -dose vials of \ndiphtheria toxoid, pertussis, and tetanus toxoid (DPT) vaccine which were contaminated after being \nopened. Thimerosal was present in acceptable limits in unopen vials of vaccine from the same lot. The \nauthors concluded that “Preservatives in multidose vials do not prevent short term bacterial \ncontamination ” and  the “only feasible and cost -effective preventative measure now available is careful \nattention to sterile technique when administering vaccines from multidose vials.”\n•In 2004, a Chiron plant that manufactured Fluvirin vaccine preserved with thimerosal was forced to close \nbecause its vaccine was contaminated with Serratia marcescens.  The closure created shortages in the \nvaccine supply and caused concern among providers and patients. In this case and others, thimerosal \nfailed to prevent bacterial growth.\n\n9 Current Research\nThimerosal safety and effectiveness\n•A more current in vitro investigation into the cytotoxic effects and \nantimicrobial activity of thimerosal was published in 2023.  The authors \nreported that thimerosal should be present in culture media at 100 μg/ml \nconcentration to achieve effective antimicrobial activity. But all tested cell \nlines lost viability completely at 4.6 µg/ mL.\n•“Overall, our study revealed Thimerosal was 333 -fold more cytotoxic to \nhuman and animal cells as compared to bacterial and fungal cells . Our results \npromote more study on Thimerosal toxicity and its antimicrobial effectiveness \nto obtain more safe concentrations in biopharmaceuticals.”\nRahimian A, Lakzaei M, Askari H, Dostdari S, Khafri A, Aminian M. In vitro assessment of Thimerosal cytotoxicity and antimicr obial activity. J Trace Elem Med \nBiol. 2023 May;77:127129. doi: 10.1016/j.jtemb.2023.127129. Epub 2023 Jan 4. PMID: 36630761.\n\n10Evidence of Thimerosal\nDevelopmental Neurotoxicity\nWallin, M. (1993). Effects of potential aneuploidy -inducing agents on microtubule assembly in vitro. \n*Mutation Research. Fundamental and Molecular Mechanisms of Mutagenesis*, 287(1), 17 –22. https:// doi.org /10.1016/0027 -5107(93)90141 -2•In 1987 the Commission of the European Communities initiated a research project on 10 \nknown or suspected spindle poisons. Thimerosal was found to cause significant \ninterference with microtubule polymerization destabilizing the spindle machinery that \nensures accurate chromosome separation during cell division. \n•This mechanistic disruption suggests direct mutagenic potential via structural \nchromosomal abnormalities, which is a known pathway to carcinogenesis or congenital \ndefects. \n•By affecting fundamental cellular structures at the molecular level, thimerosal revealed \n“strong mechanistic evidence for mutagenicity and developmental toxicity”.\n\n11\nThimerosal has been recognized as a Prop 65 chemical since 1990.CALIFORNIA EPA Proposition - 65\n•California’s Proposition 65, requires identification of chemicals known to cause cancer, birth \ndefects or other reproductive harm, and to ensure public warnings when people might be \nexposed to them. Thimerosal has been on the Prop -65 list since 1990.\n•In 2003 a petition was filed on behalf of the Bayer Corporation “for reconsideration of the \ndetermination that mercury and mercury compounds (thimerosal) as reproductive toxicants.” \n•The CA EPA responded that “The scientific evidence that thimerosal cause reproductive \ntoxicity is clear and voluminous.  Thimerosal dissociates in the body to ethyl mercury.  The \nevidence for its reproductive toxicity includes severe mental retardation or malformations \nin human offspring who were poisoned when their mothers were exposed to ethyl mercury \nor thimerosal while pregnant, studies in animals demonstrating developmental toxicity after \nexposure to either ethyl mercury or thimerosal, and data showing interconversion to other \nforms of mercury that also clearly cause reproductive toxicity.”\n\n12\nEvidence From Human Research (1)\n•A study published in Pediatrics in 2000 measured blood mercury levels in preterm and \nterm infants after administration of the Hepatitis B vaccine containing 12.5 µg ethyl \nmercury.  \n•The investigation documented elevated post -immunization concentrations relative to \npre-immunization levels in all neonates studied. Levels of blood mercury after exposure \nin low -birth -weight infants were 7.36 ( ± 4.99) µg/L.\n•One infant was found to have developed a mercury level of 23.6 µg/L, thus meeting the \nCDC criteria as a case of chemical poisoning from mercury 10µg /L.  The study subjects \nhad measurable blood Hg concentrations prior to immunization, indicating that risk \nassessment must include background mercury levels from other sources.\nStajich GV, Lopez GP , Harry SW, Sexson WR. Iatrogenic exposure to mercury after Hepatitis B vaccination in preterm infants. J .Pediatrics. 2000;136 (5):679 -81.\nCenters for Disease Control and Prevention. (2005, January 14). Case Definitions for Chemical Poisoning. MMWR Recommendations  and Reports, 54(RR -1), 1 –\n24. Retrieved from https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5401a1.htm\n\n13\nRice D, Barone S Jr. Critical periods of vulnerability for the developing nervous system: evidence from humans and animal mod els. Environ Health Perspect . \n2000;108 Suppl 3:511 -33.•Experts contend that there are “windows of vulnerability” which occur during neurological \ndevelopment and that specific types of developmental outcomes may have separate \nwindows of vulnerability. These critical periods of development have not been established \nand may be relatively short in duration.\n•The fact that thimerosal from vaccines has been documented to raise blood mercury levels \nover known thresholds where developmental effects have been documented to occur \nduring the first few months of life, means that particular \"windows of vulnerability\" may \nhave been breached.  Even minor neurological impairment can have profound societal \neffects when amortized across the entire population and life span.Evidence From Human Research (2)\n\n14 Exposure To Vaccine Level Thimerosal\nCrosses the Blood Brain Barrier and Results in Significant \nDeposition of Mercury in the Brain\n•A 2005 study funded by NIH compared brain mercury levels in infant Macaca fascicularis \nprimates exposed to: 1) injected ethyl mercury (thimerosal) and 2) equal amounts of \ningested methylmercury.\n•Ethyl mercury more rapidly converted to inorganic mercury in the brains of the primates \nwhich resulted in increasing levels of inorganic mercury.  \n•Primates exposed to ethyl mercury retained much higher levels of inorganic mercury in \ntheir brains, up to 71% vs. 10% compared to primates exposed to methyl mercury.\n•Once organic mercury compounds reach the brain tissue and dealkylate, Hg2+ (toxic \ninorganic mercury) the mercury cannot cross the blood brain barrier and becomes \ntrapped, resulting in neuroinflammation.\nBurbacher TM, Shen DD, Liberato N, Grant KS, Cernichiari E, and Clarkson T. Comparison of blood and brain mercury levels I in fant monkeys exposed to \nmethylmercury or vaccines containing thimerosal. Environmental Health Perspectives. 2005;113(8):1015 -1021.\n\n15 Inorganic Mercury and the Developing Brain \nThimerosal is ~49.6% \nmercury by weight•A recent review outlined evidence from human and animal studies which estimated the \ninorganic mercury half -life in human brains of at least five to 27 years. (1)\n•The impact of mercury exposure to the developing brain interferes with neuronal \nproliferation, migration, differentiation, synaptogenesis, tightly regulated apoptosis, and \nother processes vital to the formation and functioning of the nervous system which can \nresult in lifelong neurodevelopmental impacts. \n•Exposure during the first trimester of pregnancy may result in deficits or defects very \ndifferent from those developed by someone who is exposed during the third trimester of \npregnancy. “There may never be a safe level of mercury exposure, especially for an \nunborn child.” (2) \n1.Rooney JP . The retention time of inorganic mercury in the brain --a systematic review of the evidence. Toxicol Appl Pharmacol. 2014 Feb 1;274(3):425 -35. \n2. Pletz J, Sánchez -Bayo F, Tennekes HA. Dose -response analysis indicating time -dependent neurotoxicity caused by organic and in organic mercury -Implications \nfor toxic effects in the developing brain. Toxicology. 2016 Mar 10;347 -349:1 -5. doi: 10.1016/j.tox.2016.02.006. Epub 2016 Mar 2.  PMID: 26945727.\n\n16 Mercury Content In\nThimerosal -containing Flu Vaccines\n•Thimerosal is ~49.6% mercury by weight with a concentration of 0.01% thimerosal in \nvaccines. This equates to 100 µg/mL of thimerosal and 50 µg/mL of ethyl mercury per ml. \n•The EPA’s Toxicity Characteristic Leaching Procedure (TCLP) determines whether a \nsubstance is considered hazardous waste based on its potential to leach toxic chemicals \ninto groundwater.\n•According to EPA TCLP Mercury Threshold (40 CFR § 261.24) the regulatory threshold for \nmercury (D009) under TCLP is: 0.2 mg/L (200 parts per billion, or 200 µg/L).\n•Flu vaccine mercury concentration (~50,000 µg/L) is 250 times greater than the TCLP limit. \nTherefore, thimerosal -containing vaccines exceed the TCLP threshold by orders of \nmagnitude and are classified as D009 Hazardous Waste \n17 Vaccine Mercury: Disposal Guidelines\n\n18\nPopulation Susceptibility Factors \nFetus / Developing InfantRapid neurodevelopment, immature blood -brain barrier, low glutathione, \nhigh brain accumulation\nPregnant Women Placental transfer, fetal susceptibility, breast milk transfer\nYoung Children Higher exposure per kg, immature detoxification systems\nOlder Adults Reduced renal clearance, pre -existing neurodegenerative conditions\nGenetically Susceptible Impaired detox (e.g., GST, MTHFR, APOE4), mitochondrial dysfunction\nHigh Fish Consumers Bioaccumulation through predatory fish, dietary exposure\nOccupationally Exposed Workers Inhalation exposure, chronic accumulation (e.g., dentists, miners)Susceptible Populations\n\n19 Summary (1)\n•Mercury is the third most toxic element on earth, behind polonium and plutonium, \nand has no physiological role in the human body. \n•Thimerosal was grandfathered for use without adequate safety testing by the FDA. \n•Thimerosal is not “generally recognized as safe or effective” (GRASE) by the FDA OTC \nDivision since 1998.\n•There is evidence that thimerosal is not an effective preservative at vaccine levels.\n•Thimerosal can cross the placenta and blood brain barriers and converts to inorganic \nmercury in the brain at higher levels that methyl mercury. \n•Studies have identified infants with blood levels after exposure to thimerosal that \nbreach CDC guidelines for a case of mercury chemical poisoning. \n20 Summary (2)\n•Thimerosal is recognized as a developmental and reproductive toxicant and is listed as \na chemical on the California Proposition 65 list since 1990.\n•Unused doses of  thimerosal preserved flu shots must be disposed of as hazardous \nwaste.\n•Tremendous progress has been made in removing thimerosal, but more than 60,000 \npregnant mothers receiving Medicaid in the 2019 -2020 flu season received TCVs.\n•We currently have enough thimerosal free flu vaccines to recommend that all \npregnant women, infants and children receive only thimerosal free vaccines. \n•After a critical appraisal of this issue almost 25 years ago, the prestigious Institute of \nMedicine made this same recommendation. \n•Removing a known neurotoxin from being injected into our most vulnerable \npopulations is a good place to start with Making America Healthy Again.", "summary": "ACIP 2025 BusinessThimerosal as a Vaccine Preservative Prepared for the  Advisory Committee for  Immunization PracticesLyn Redwood RN, MSN, FP (Retired)  2The Food and Drug Administration  Modernization Act of 1997 •Compiled list of drugs and foods that contained intentionally introduced  mercury compounds •Provided quantitative and qualitative analysis of mercury compounds •Report included 219 products which included 11 biologics and immunoglobulin  therapies Ref: U.S. Congress. (1997,…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-25-26-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-06-25-26/05-influenza-redwood-508.pdf", "doc_date": "2025-06-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 20}
{"title": "01 Petersen chikungunya 508", "content": "Partial Evidence to Recommendations for use of \nchikungunya vaccines among persons in U.S. \nterritories at risk for chikungunya virus \ntransmissionNational Center for Emerging and Zoonotic Infectious Diseases\nDr. Lyle Petersen\nDirector, Division of Vector -Borne Diseases\nAdvisory Committee on Immunization Practices meeting\nJune 26, 2025\n•Two licensed chikungunya vaccines \n-Live attenuated vaccine licensed in November 2023 for use in persons aged ≥18 \nyears  (manufactured by Valneva)\n-Virus -like particle vaccine licensed in February 2025 for use in persons aged ≥12 \nyears (manufactured by Bavarian Nordic)\n•Chikungunya Vaccines Work Group formed in May 2022\n-Approved recommendations exist for use of vaccines in travelers and laboratory \nworkers\n-Recent topic under discussion has been use of chikungunya vaccines in persons in \nU.S. territories and states at risk for chikungunya virus transmissionBackground\nEvidence to Recommendations ( EtR) for use of \nchikungunya vaccines among persons in U.S. territories \nat risk for chikungunya virus transmission: \nPublic health problem and value of a vaccine\nEtR framework\nEtR Domain Question\nPublic health problem •Is the problem (chikungunya) of public health importance?\nBenefits and harms•How substantial are the desirable anticipated  effects of CHIK -VLP?\n•How substantial are the undesirable anticipated  effects?\n•Do the desirable effects outweigh the undesirable  effects?\n•What is the overall certainty of this evidence for the critical outcomes? \nValues•Does the target population feel the desirable effects are large relative to \nthe undesirable effects?\n•Is there important variability in how patients value theoutcomes?\nAcceptability •Is the intervention acceptable to keystakeholders?\nResource use •Is the intervention a reasonable and efficient allocation ofresources?\nEquity •What would be the impact of the intervention on health equity?\nFeasibility •Is the intervention feasible to implement?\nPublic Health Problem\nQuestion: Is the problem of public health importance?\nKey related questions include: \n•Are the consequences of the problem serious? \n•Are a large number of people affected by the problem? \n•Is the problem related to emerging diseases …. or epidemic potential? \nChikungunya virus transmission\nCountries and territories with current or past transmission of chikungunya virus\nGlobally, ~620,000 cases \nreported in 2024 but likely \nunderestimate\n Outbreaks can be   \nlarge and explosive\n•One-third to three -\nquarters of po pulation \naffected\n•Substantial morbidity\n•Stresses healthcare \ncapacity\nNo highly effective alternatives to vaccination for \ndisease control\nAcknowledgement: Claudia Colon -Burgos & Coral Rosado- Santiago, CDC Dengue Branch•Mosquito prevention and control \nmeasures\n-Use of insect repellent challenging as \nrequires daily use during outbreaks\n-Source reduction important but difficult to remove enough water -\nholding containers where mosquitoes \nlay eggs\n•Other prevention measures have \nhad variable impact\n•Fever and joint pain\n-Arthralgia often severe and can be \ndebilitating\n-Multiple joints involved, most \ncommonly hands and feet\n•Other symptoms include \nheadache, myalgia, fatigue, rash, \nabdominal pain, and vomiting\n•No anti -viral treatment\n-Supportive managementImpact of acute illness\nImage above from : https://www.paho.org/en/topics/chikungunya\n•Rare serious complications (e.g., cardiac, \nrenal, ocular, neurologic illness)\n•Hospitalization rate ~3%\n•Case fatality rate: 0.01% –0.5% \n•Serious outcomes mostly in older adults and young infantsImpact of disease: severe presentations \nImages from : https://www.paho.org/en/topics/chikungunya\nImpact of disease: Arthralgia that persists or recurs\n•Most patients have arthralgia that resolves in \n7–10 days\n•Arthralgia sometimes persists or relapses with \nother symptoms e.g., fatigue\n\nImpact of disease: Arthralgia that persists or recurs\nBased on recent meta -analysis (Lindsey N. Chronic arthralgia after chikungunya. US Advisory Committee on Immunization Practices meeting, June 2023)*\n*Rates likely overestimated as background rate of arthralgia in the population could not be taken into account51% 3 months\npost -infection12 months\npost -infection\n38%Acute \nillness\n100% \nChikungunya previously documented in five U.S. territories \nand affiliated states\n•Puerto Rico\n•United States Virgin Islands (USVI)\n•American Samoa \n•Federated States of Micronesia \n•Marshall Islands\nReported chikungunya cases by month of illness onset, \nPuerto Rico, 2014 –2015*\n050010001500200025003000\nJan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec\n2015 2014*Cases reported to Puerto \nRico Department of Health\nReported chikungunya cases by year and case status, \nPuerto Rico, 2014 –2020\n0200040006000800010000\n2014 2015 2016 2017 2018 2019 2020Probable\nConfirmed\nLast laboratory -confirmed \nsymptomatic clinical case\n•Seroprevalence study indicated \n~30% population infected during \noutbreak1\n•Based on 30% seroprevalence \nrate, ~1 million persons infected, \nand 65% –85% of chikungunya \nvirus infections being symptomatic\n-~650,000 –850,000 clinical \ncases Estimated number of clinical cases in Puerto Rico \nchikungunya outbreak\n1. 1,268 of 4,035 participants (Adams LE at al, PLoS  NTD 2022);     \nEstimated 650,000– 850,000 \nclinical cases during the outbreak \nin Puerto Rico* \n*Based on ~30% post -outbreak population seroprevalence (Adams LE at al, PLoS NTD 2022) and 65% –85% of infections being symptomatic\nEstimated hospitalizations and deaths in \nchikungunya outbreak in Puerto Rico, 2014 –2015 \n19,500– 25,500 hospitalizations* 65-85 deaths#\n*Based on 3% hospitalization rate#Based on 0.01% case -fatality rate\n•Federated States of Micronesia (Yap State): 2013– 2014 \n•USVI: 2014– 2015\n•American Samoa : began June 2014\n•Marshall Islands: began February 2015Chikungunya in other U.S. territories and affiliated states*\n*ACIP presentation, June 2024 (https://www.cdc.gov/acip/downloads/slides -2024- 06-26-28/03- Chikungunya -Hills -508.pdf)\nSummary: Is chikungunya of public health importance \nin U.S territories with risk of transmission?\n1. Acute illness can be severe, hospitalizations can occur (particularly in \nvulnerable groups), and arthralgia can persist for months or years\n2. Timing of next outbreak is unknown but is likely to evolve rapidly and might affect a substantial proportion of population\n3. Outbreaks can impact health services through patient loads and staff absenteeism\n4. No highly effective control measures exist apart from vaccination \nQuestion: Is the problem of public health importance?\n□No\n□Probably no\n□Probably yes\n□Yes\n□Varies\n□Don’t know\nValues and preferences\n1. Target population perception of value\nDo potential vaccine recipients feel that the desirable effects are large relative \nto undesirable effects?\n2. Uncertainty around target population perception of value\nIs there important uncertainty about, or variability in, how much people value the main outcomes? Values and preferences\nValue of a chikungunya vaccine for residents of Ponce, \nPuerto Rico: Study methods\n•Data collected as part of larger study mos quito -borne disease study* \n•Chikungunya component conducted in 2024, ~10 years after chikungunya \noutbreak  in Puerto Rico\n•Included 2,437 individuals or caregivers aged 1– 56 years \n•Asked basic question about interest in vaccination with hypothetical chikungunya vaccine if free of charge or at ≤$10, and reasons if not \ninterested or unsure\n*Adams LE et al. PLoS  Negl  Trop Dis 2022\nIf there was an approved chikungunya vaccine available \nin Puerto Rico, free of charge or at low cost ($ 10 or less), would you get vaccinated (N=2,437)?\nNo Unsure Yes71%23%\n7%Participants who had \ncompleted at least some \nhigher education or had no \nhistory of chikungunya \nmore likely to respond \n“no” or “don’t know”*\n*Preliminary analyses\nWhat are the reasons why you would not be interested \nor are not sure if you would be interested in getting vaccinated against chikungunya?*\n*Could select ≥1 reason0510152025303540Percentage\n•Part of larger population -based household study\n•Conducted soon after end of outbreak in June 2015\n•Included 966 participants aged 1– 91 years\n•Subjects or caregivers questioned about interest in \nreceiving a hypothetical chikungunya vaccine\n•Estimates calibrated to age and sex of USVI population Value of chikungunya vaccine in United States Virgin Islands\nPopulation of 106,405 in 2010\nCurren EJ et al. Am J Trop Med Hyg 2022 \n010203040506070Adjusted proportions with 95% CI\nVaccine interest56% interested in vaccineVaccine interest among participants (adjusted proportion)\n25%\n19%\nInterested (n=520)          Not interested (n=258)        Unsure (n=188)        \n010203040506070Adjusted proportions with 95% CI\nVaccine interest56% interested in vaccineVaccine interest among participants (adjusted proportion)\n25%\n19%\nInterested (n=520)          Not interested (n=258)        Unsure (n=188)        Persons aged ≥40 years less \nlikely to be interested vs. persons aged 0 –19 years\nReasons for potential lack of interest in vaccine among \nthose not interested or uncertain about vaccination (N=446)\n•Wanting more safety information: 47% (95% CI: 41– 52%)\n•Lack of concern for getting disease: 16% (95% CI: 13– 20%)\n•Already had chikungunya disease: 10% (95% CI: 7– 13%) \n•Majority of participants indicated interested in a hypothetical vaccine at time \nsurveys implemented\n-Higher interest in Puerto Rico (71%) v s. USVI (56%) possibly influenced by timing of \nsurveys in relation to outbreaks and general vaccine uptake differences in two \nterritories\n•For respondents potentially not interested in vaccine, key concern was \nneeding a better understanding of vaccine safety \n-Will be important to provide resources and education on vaccine safety if \nchikungunya vaccine introducedSummary\nQuestion: Does the target population feel that the \ndesirable effects of vaccination are large relative to undesirable effects? \n□No\n□Probably no\n□Probably yes\n□Yes\n□Varies\n□Don’t know\nQuestion: Is there important uncertainty about or \nvariability in how much people value the main outcomes?\n□Important uncertainty or variability\n□Probably not important uncertainty \nor variability\n□No important uncertainty or variability\n□No known undesirable outcomes\nUpdate on safety of live attenuated chikungunya \nvaccine in older personsNational Center for Emerging and Zoonotic Infectious Diseases\n\nSerious adverse events in older persons\n•Status as of April 2025 ACIP meeting\n-6 serious adverse events (SAEs) occurred in US persons aged ≥65 years during 2024*\n-Discussed at ACIP meeting on April 16 and CDC determined age ≥65 years is \nprecaution to vaccination with live attenuated chikungunya vaccine\n•Updates since April 2025 ACIP meeting\n-In the 3 weeks following ACIP meeting, 11 additional SAEs reported internationally in \npersons aged 62 –89 years, most with underlying medical conditions# \n-European Medicines Agency recommended temporary pause in vaccine use in ages ≥65 years (May 7)\n-FDA and CDC recommended temporary pause in the live, attenuated vaccine use in ages ≥60 years to allow investigations of reports (May 9)\n¥\n-Awaiting outcome of FDA investigations\n*Reported through Vaccine Adverse Events Reporting System (VAERS)     #Mainly from Reunion where large outbreak occurring\n¥FDA and CDC Recommend Pause in Use of Ixchiq  (Chikungunya Vaccine, Live) in Individuals 60 Years of Age and Older While Postmarketing  Safety Reports are Investigated | FDA\n \nACIP Chikungunya Vaccines Work Group\nArboviral Diseases Branch, CDC\n•Sarah Guagliardo\n•Susan Hills\n•Erin Staples\nDengue Branch, CDC\n•Laura AdamsAcknowledgements\nFor more information, contact CDC\n1-800- CDC- INFO (232 -4636)\nTTY:  1 -888- 232- 6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.", "summary": "Partial Evidence to Recommendations for use of  chikungunya vaccines among persons in U.S.  territories at risk for chikungunya virus  transmissionNational Center for Emerging and Zoonotic Infectious Diseases Dr. Lyle Petersen Director, Division of Vector -Borne Diseases Advisory Committee on Immunization Practices meeting June 26, 2025 •Two licensed chikungunya vaccines  -Live attenuated vaccine licensed in November 2023 for use in persons aged ≥18  years  (manufactured by Valneva) -Virus…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-25-26-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-06-25-26/01-Petersen-chikungunya-508.pdf", "doc_date": "2025-06-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 37}
{"title": "01 Jackson Anthrax 508", "content": "Introduction to the Anthrax Vaccine Work Group\nBrendan Jackson, MD, MPH\nCaptain, U.S. Public Health Service\nPrincipal Deputy Director\nDivision of High -Consequence Pathogens and Pathology\nJune 26, 2025\nAdvisory Committee on Immunization PracticesNational Center for Emerging and Zoonotic Infectious Diseases\n\n•Bacillus anthracis , the causative agent of anthrax, is an endospore -forming \nbacterium found naturally in soil around the world\n•Humans are most often infected by exposure to infected animals or animal \nby-products via cutaneous, gastrointestinal, or inhalational routes\n•Bacillus anthracis isa Tier 1 select agent\n-Potential for use as a bioweapon\n-High case fatality rate\n-Ability to cause great harm to public health and safety, particularly when \naerosolizedPublic Health Problem \n•Vaccine : Anthrax vaccine adsorbed, adjuvanted (AVA,A) ( Cyfendus )\n-Second -generation anthrax vaccine\n-Licensed in July of 2023 for post -exposure prophylaxis (PEP) following exposure \nto Bacillus anthracis in adults aged 18 to 65\n•Work Group Objective: Review existing safety and immunogenicity data to \ndevelop recommendations for ACIP to consider for domestic use of AVA,A \nfor anthrax PEPAnthrax Vaccine Work Group \nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention.\nThank you.", "summary": "Introduction to the Anthrax Vaccine Work Group Brendan Jackson, MD, MPH Captain, U.S. Public Health Service Principal Deputy Director Division of High -Consequence Pathogens and Pathology June 26, 2025 Advisory Committee on Immunization PracticesNational Center for Emerging and Zoonotic Infectious Diseases  •Bacillus anthracis , the causative agent of anthrax, is an endospore -forming  bacterium found naturally in soil around the world •Humans are most often infected by exposure to infected…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-25-26-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-06-25-26/01-Jackson-Anthrax-508.pdf", "doc_date": "2025-06-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 4}
{"title": "01 MMRV safety summary 508", "content": "1 \n \nMMRV Vaccine Safety  \n \nContents  \nSummary  ................................ ................................ ................................ ................................ ......  1 \nCochrane Review  ................................ ................................ ................................ ...........................  2 \nGeneral safety  ................................ ................................ ................................ ...............................  3 \nFebrile convulsion/febrile seizure  ................................ ................................ ................................ .... 6 \nStudies performed outside of the United States  ................................ ................................ ................  8 \nClinical Trial data  ................................ ................................ ................................ .........................  10 \n \nSummary  \nThe measles -mumps -rubella -varicella (MMRV) vaccine (ProQuad®, Merck) was licensed in the \nUnited States in 2005 for use in children 12 months through 12 years of age. In 2006, the \nAdvisory Committee on Immunization Practices (ACIP) recommended MMRV as an option for \nboth the first and second doses of measles, mumps, rubella, and varicella vaccination. However, \npost -licensure safety surveillance identified an increased risk of febrile seizures 5 –12 days aft er \nthe first dose in children aged 12 –23 months compared to those receiving separate MMR and \nvaricella (MMR + V) vaccines. Based on this finding, ACIP updated its guidance in 2009.  \nACIP currently recommends that MMR  and varicella vaccines be given separately for the first \ndose in children 12 –47 months ; however , MMRV may be  used if parents or caregivers request a \npreference. Compared with use of MMR vaccine and varicella vaccine at the same visit, use of \nMMRV vaccine results in one fewer injection but is associated with a higher risk for fever and \nfebrile seizures 5 -12 days after the first dose among children aged 12 -23 months . Use of MMR \nvaccine and varicella vaccine avoids this increased risk for fever and febrile seizures following \nMMRV vaccine.  Studies of febrile seizures after vaccination with first dose of MMRV vaccine \nhave not been done in older children, but experts agree that this increased risk of fever and \nfebrile seizures during the 5 -12 days after first dose vaccination likely also occur s in ch ildren \naged 24 -47 months because that is the biologic window of vulnerability for febrile seizures in \nchildren (approximately 97% of febrile seizures occur in children aged <4 years). First febrile \nseizures are uncommon after age 4 years  (MMRV Questions and Answers for Healthcare \nProviders | CDC ). Either MMRV or MMR + V may be used for the second dose or for children \naged 4 years and older  (Use of Combination Measles, Mumps, Rubella, and Varicella Vaccine ). \nOver the past 15+ years  and multiple studies , mild fever and rash are the most common ly \nreported adverse events  following MMRV vaccination . The primary safety concern is an \nincreased risk of febrile seizures following the first dose in children aged 12 -23 months.  This risk \n2 \n \nis estimated at 1 additional seizure occurring 5 -12 days after vaccination per 2,300 -2,600 \nvaccinated children  compared to those receiving MMR + V separately  (Use of Combination \nMeasles, Mumps, Rubella, and Varicella Vaccine ).  These events resolve without long -term \nconsequences  (Measles, Mumps, Rubella, Varicella (MMRV) Vaccine Safety | Vaccine Safety | \nCDC). No increased seizure risk has been observed with the second dose or in children aged 48 \nmonths or older.  \nSeveral clinical trials have also evaluated the safety of MMRV when administered concomitantly \nwith other routine childhood vaccines , including pneumococcal conjugate vaccine (PCV -7), \nmeningococcal conjugate vaccines (MenACWY , MenC), and DTaP -containing vaccines. These \nstudies found no increase in serious adverse events or clinically meaningful differences in \nreactogenicity .  International surveillance and real-world  data from Canada and Europe have  \nconfirm ed the most common adverse events as mild fever and rash , along with the increased \nrisk of febrile seizure as the only serious adverse event  following MMRV vaccination. Although \nrare case s of encephalitis and death have been reported after MMRV vaccination, no direct link \nbetween these events and the vaccine has been established in persons with healthy immune \nsystems . \nCochrane Review  \n• Di Pietrantonj C, Rivetti A, Marchione P , Debalini MG, Demicheli V. Vaccines for measles, \nmumps, rubella, and varicella in children.  Cochrane Database Syst Rev . \n2021;11(11):CD004407. Published 2021 Nov 22. doi:10.1002/14651858.CD004407.pub5  \no Authors searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the \nCochrane Library 2019, Issue 5), which includes the Cochrane Acute Respiratory \nInfections Group's Specialised Register, MEDLINE (1966 to 2 May 2019), Embase \n(1974 to 2 May 2019), th e WHO International Clinical Trials Registry Platform (2 May \n2019), and ClinicalTrials.gov (2 May 2019).  \no Includes randomized  controlled trials (RCTs), controlled clinical trials (CCTs), \nprospective and retrospective cohort studies (PCS/RCS), case-control studies (CCS), \ninterrupted time-series (ITS) studies, case cross-over (CCO) studies, case-only \necological method (COEM) studi es, self-controlled case series (SCCS) studies, person-\ntime cohort (PTC) studies, and case-coverage design/screening methods (CCD/SM) \nstudies, assessing any combined MMR or MMRV / MMR+V vaccine given in any \ndose, preparation or time sche dule compared with no intervention or placebo, on \nhealthy children up to 15 years of age.  \no Seizure:  The analyses provide evidence supporting an association between \nMMR/MMR+V/MMRV vaccines (Jeryl Lynn strain) and febrile seizures. Febrile \nseizures normally occur in 2% to 4% of healthy children at least once before the \nage of 5. The attributable risk febri le seizures vaccine‐induced is estimated to be \nfrom 1 per 1700 to 1 per 1150 administered doses.  \n3 \n \no ITP: ITP can happen after natural measles infection.  The analyses provide evidence \nsupporting an association between MMR  vaccination and ITP .  However, the risk of \nITP after vaccination is smaller than after natural infection with these viruses. Natural \ninfection of ITP occur in 5 cases per 100,000 (1 case per 20,000) per year. The \nattributable risk is estimated about 1 case of ITP per 40,000 adm inistered MMR \ndoses.
 The overall meta-analysis estimate of association between MMR \nvaccination and ITP in children aged 9 to 23 months was RR 4.21 (95% CI 2.28 to \n7.78). There was no statistical evidence in children aged 4 to 6 y ears ( RR 3.06, 95% CI \n0.42 to 22.30), and no statistical evidence of association between MMRV \nvaccination and ITP in children aged 9 to 23 months ( RR 2.87, 95% CI 0.78 to 10.56).  \nThe latter two results came from one study ( db-O'Leary 2012 ). \nGeneral safety  \n• Klopfer SO, Stek JE, Petrecz M, et al. Analysis of safety data in children after receiving two \ndoses of ProQuad® (MMRV).  Vaccine . 2014;32(52):7154 -7160. \ndoi:10.1016/j.vaccine.2014.08.067  \no Safety data from five clinical studies were combined for all children who were \nscheduled to receive two doses of MMRV ∼3-6 months apart. All vaccinated children \nwere followed for safety following each dose of MMRV.  \no Of 3112 children who received a first dose of MMRV, 2780 (89.3%) received a second \ndose of MMRV. Overall, 70.5% and 57.7% of children reported ≥1 adverse \nexperiences following first and second doses of MMRV, respectively . Injection ‐site \nredness  was statistically significantly higher postdose 2 than postdose 1, while \ninjection ‐site pain/tenderness  was statistically significantly higher postdose 1 \ncompared to postdose 2. Rashes  were statistically significantly lower postdose 2 \ncompared to postdose 1. Ten febr ile seizures  (8 postdose 1, 2 postdose 2) were \nreported following MMRV vaccination. The incidence of febrile seizures postdose 1 \nof MMRV was 0.26% (8/3019) compared to 0.07% (2/2695) postdose 2 of MMRV.  \no Author’s conclusions: a dministration of two doses of MMRV has an acceptable safety \nprofile in children 12 to 23 months of age. There is a small increase in the risk of \nfebrile seizures following the first dose of MMRV as compared to the component \nvaccines, but the risk for any i ndividual child is relatively low.  \n• Klein NP , Lewis E, Fireman B, et al. Safety of measles -containing vaccines in 1 -year -old \nchildren.  Pediatrics . 2015;135(2):e321 -e329. doi:10.1542/peds.2014 -1822  \no Study children were aged 12 to 23 months in the Vaccine Safety Datalink from 2000 \nto 2012. Nine study outcomes were investigated : 7 main outcomes (anaphylaxis, \nITP, ataxia, arthritis, meningitis/encephalitis, acute disseminated \nencephalomyelitis, and Kawasaki disease), seizure, and fever.  Comparing MMRV \nwith MMR + V, relative risk was estimated by using stratified exact binomial tests. \nSecondary analyses examined post -MMRV or MMR + V risk versus comparison \n4 \n \nintervals; risk and comparison intervals were then contrasted for MMRV versus \nMMR+V.  \no Authors  evaluated 123,200 MMRV and 584,987 MMR + V doses . Comparing MMRV \nwith MMR + V, risks for the 7 main outcomes were not significantly different.  \nSeveral outcomes had few or zero postvaccination events. Comparing risk versus \ncomparison intervals, ITP risk was higher after MMRV (odds ratio [OR]: 11.3 [95% \nconfidence interval (CI): 1.9 to 68.2]) and MMR + V (OR: 10 [95% CI: 4.5 to 22.5]) \nand ataxia risk was lower after both vaccines (MMRV OR: 0.8 [95% CI: 0 .5 to 1]; \nMMR + V OR: 0.8 [95% CI: 0.7 to 0.9]).  Compared with MMR + V, MMRV increased \nrisk of seizure and fever 7 to 10 days after vaccination.  \no Author’s conclusions: This study did not identify any new safety concerns comparing \nMMRV with MMR + V or after either the MMRV or the MMR + V vaccine. This study \nprovides reassurance that these outcomes are unlikely after either vaccine.  \n• Ma SJ, Li X, Xiong YQ, Yao AL, Chen Q. Combination Measles -Mumps -Rubella -Varicella \nVaccine in Healthy Children: A Systematic Review and Meta -analysis of Immunogenicity and \nSafety.  Medicine (Baltimore) . 2015;94(44):e1721. doi:10.1097/MD.0000000000001721  \no Authors  searched PubMed, Embase, BIOSIS Previews, Web of Science, Cochrane \nLibrary, and other databases through September 9, 2014. Eligible randomized \ncontrolled trials (RCTs) were selected and collected independently by 2 reviewers. \nMeta -analysis was conducted u sing Stata 12.0 and RevMan 5.3.  \no Incidences of any serious adverse events (SAEs) were around 1% in all the groups; \nonly about one -tenth of the events were considered to be related to vaccination \nstudied. About half of the related SAEs were febrile seizures. The incidence of related \nfebril e seizure was under 0.8 % in MMRV groups and under 0.5‰ in MMR + V/MMR \ngroups. No statistical difference was found between groups with no evidence of \nheterogeneity . No related fatal SAE was reported in any studies included.  \no Well tolerated safety profiles were demonstrated except higher incidence of fever \n(relative risks 1.12 –1.60) and measles/rubella ‐like rash (relative risks 1.44 –1.45) in \nMMRV groups.  \no Author’s conclusions: MMRV had comparable immunogenicity and overall safety \nprofiles to MMR + V/MMR in healthy children based on current evidence.  \n• Woo EJ, Winiecki SK, Arya D, Beeler J. Adverse Events After MMR or MMRV Vaccine in \nInfants Under Nine Months Old.  Pediatr Infect Dis J . 2016;35(8):e253 -e257. \ndoi:10.1097/INF.0000000000001201  \no The Vaccine Adverse Event Reporting System  was searched  for reports of measles, \nmumps and rubella vaccine (MMR) or measles, mumps, rubella and varicella vaccine \n(MMRV) vaccination in children less than 9 months of age. A clinical assessment of \neach report was conducted and the frequency, range, onset time and severity of \nadverse events  was summarized . \n5 \n \no After excluding 346 reports because they were duplicates or because they contained \ninsufficient information about the child's age or vaccine(s), authors  retained 204 \nreports in the analysis, including 35 (17%) that were serious. Among the 169 \nnonserious reports, more than half (88; 52%) described a vaccination error without \nany adverse event per se. Other nonserious reports described fever, injection \nreactions and gastrointestinal symptoms . Serious adverse events included \ndevelopmental disorders, fever and fussiness. There were 44 reports of fever, but \nonly 4 cases began 5 ‐12 days after immunization, the peak risk window. The vast \nmajority of fever reports listed concomitant vaccines, such as diphtheria and \ntetanus toxoids, acellular or whole ‐cell pertussis vaccine.  \no Author’s conclusions:  This review did not identify any major safety concerns. These \nfindings may facilitate discussions about the risks and benefits of vaccinating infants \nwho are potentially exposed to this life -threatening disease.  \n• Safety Surveillance of Varicella Vaccines in the Vaccine Adverse Event Reporting System, United \nStates, 2006 –2020 - PMC  \no US VAERS reports received after administration of VAR and MMRV during 2006 -2020 \nwere identified. Reports were analyzed by vaccine type, age, seriousness, most \ncommon adverse events (AEs), and concomitant vaccines. Medical records of \nselected reports of AEs of special interest were reviewed and empirical Bayesian data \nmining to identify disproportionally reported AEs  was conducted . \no During 2006 -2020, approximately 132.8 million VAR doses were distributed; 40 684 \nreports were received in VAERS (30.6/100 000 doses distributed), with 4.1% \nclassified as serious (1.3/100 000 doses distributed). Approximately 35.5 million \nMMRV doses were di stributed; 13 325 reports were received (37.6/100 000 doses \ndistributed) with 3.3% classified as serious (1.3/100 000 doses distributed). The most \ncommon adverse health events after both VAR and MMRV were injection site \nreactions (31% and 27%), rash (28% a nd 20%), and fever (12% and 14%), \nrespectively. Vaccination errors accounted for 23% of reports after VAR \nadministration and 41% after MMRV administration, but ≥95% of them did not \ndescribe an adverse health event. AEs associated with evidence of vaccine s train \nvaricella -zoster virus (vVZV) infection included meningitis, encephalitis, herpes \nzoster, and 6 deaths (all in immunocompromised persons with contraindications for \nvaccination). No new or unexpected AE was disproportionally reported . \no Author’s conclusions: No new or unexpected safety findings were detected for VAR \nand MMRV given as recommended, reinforcing the favorable safety profiles of these \nvaccines. Providers should obtain specimens for viral testing and strain -typing for \nserious AEs if they consider vV ZV as the possible causative agent.  \n• Vittrup DM, Charabi S, Jensen A, Stensballe LG. A systematic review and meta -analysis of \nadverse events following measles -containing vaccines in infants less than 12 months of \nage. Vaccine . 2025;47:126687. doi:10.1016/j.vaccine.2024.126687  \n6 \n \no EMBASE and PubMed were searched in February 2021 , and the search was  updated \nin February 2024. With the exception of case reports, we included all English -written \noriginal studies published >1985 that contained frequency measures on adverse \nevents (AEs) within 56  days following MCV1 in infants <12  months of age. We \nidentified all common AEs and their frequencies and combined these across studies \nin a meta -analysis. The effect of measles strain and vaccine valency  was also \nevaluated.  \no 24 studies were included in the analysis: 18 randomized controlled trials (RCTs), \nthree interventional studies, and three observational studies. Only one RCT was \nplacebo -controlled. Commonly reported AEs were injection site reactions, fever, \nrash, gastrointestinal symptoms, respiratory t ract symptoms, conjunctivitis, and \nsymptoms related to the general condition of the infant . The frequency of any AE \nwas generally <10  %; however, the placebo ‐controlled trial showed no difference \nbetween MCV1 and placebo ‐injected infants. Edmonston B strains and measles ‐\nmumps ‐rubella ‐varicella vaccine (MMRV) were associated with a higher rate of \nhigh fever >39  °C. \no Most AEs occurred in <10  % of infants receiving MCV1  at < 12 months of age. The \nplacebo -controlled trial suggested no excess reactogenicity following early MCV. \nMeasles strain and vaccine valency may affect AE risks, but other factors such as \nsocioeconomic  status, race, and setting could also explain this finding, as these were \nnot equally distributed between studies. Caution is advised when interpreting \nfindings from studies without a placebo group.  \nFebrile convulsion/febrile seizure  \n• Jacobsen SJ, Ackerson BK, Sy LS, et al. Observational safety study of febrile convulsion \nfollowing first dose MMRV vaccination in a managed care setting.  Vaccine . \n2009;27(34):4656 -4661. doi:10.1016/j.vaccine.2009.05.056  \no Children ages 12 –60 months who received a first dose of MMRV in February \n2006 –June 2007 in a managed care organization were included in the study. \nSubjects were optimally matched on age, sex, and calendar date of vaccination to \nchildren who received MMR  + V concomitantly in November 2003 –January 2006, \nbefore MMRV licensure. Potential cases of febrile convulsion were identified \nthrough administrative data and adjudicated by expert panel, according to pre -\nspecified criteria.  \no During the 30 days post -vaccination, there were 128 and 94 potential convulsion \ncases among the 31,298 children in the MMRV and MMR+V cohorts, \nrespectively. After review of available medical charts and adjudication, there \nwere 84 cases of confirmed febrile  convulsion, 44 (1.41/1000) and 40 \n(1.28/1000) in the MMRV and MMR+V cohorts, respectively (RR=1.10, 95% \nCI=0.72, 1.69). In days 5 -12 following vaccination, a pre -specified period of \n7 \n \ninterest, the respective numbers were 22 (0.70/1000) and 10 (0.32/1000) \n(RR=2.20, 95% CI=1.04, 4.65).  \no These data suggest that the risk of febrile convulsion is increased in days 5 ‐12 \nfollowing vaccination with MMRV as compared to MMR+V given separately \nduring the same visit, when post ‐vaccination fever and rash are also increased \nin clinical trials.   \n• Klein NP , Fireman B, Yih WK, et al. Measles -mumps -rubella -varicella combination vaccine \nand the risk of febrile seizures.  Pediatrics . 2010;126(1):e1 -e8. doi:10.1542/peds.2010 -\n0665  \no Using 2000 –2008 Vaccine Safety Datalink data, authors assessed seizures and \nfever visits among children aged 12 to 23 months after MMRV and separate \nMMR + varicella vaccines. Authors  compared seizure risk after MMRV vaccine to \nthat after MMR + varicella vaccines by using Poisson regression as well as with \nsupplementary regressions that incorporated chart -review results and self -\ncontrolled analyses.  \no MMRV vaccine recipients (83 107) were compared with recipients of MMR + \nvaricella vaccines (376 354). Seizure and fever significantly clustered 7 to 10 days \nafter vaccination with all measles -containing vaccines but not after varicella \nvaccination alone. S eizure risk during days 7 to 10 was higher after MMRV than \nafter MMR + varicella vaccination (relative risk: 1.98 [95% confidence interval: \n1.43 –2.73]). Supplementary analyses yielded similar results. The excess risk for \nfebrile seizures 7 to 10 days after  MMRV compared with separate MMR + \nvaricella vaccination was 4.3 per 10 000 doses (95% confidence interval: 2.6 –5.6).  \no Among 12 ‐ to 23 ‐month ‐olds who received their first dose of measles ‐\ncontaining vaccine, fever and seizure were elevated 7 to 10 days after \nvaccination. Vaccination with MMRV results in 1 additional febrile seizure for \nevery 2300 doses given instead of sepa rate MMR + varicella vaccines.  \n• Klein NP , Lewis E, Baxter R, et al. Measles -containing vaccines and febrile seizures in \nchildren age 4 to 6 years.  Pediatrics . 2012;129(5):809 -814. doi:10.1542/peds.2011 -3198  \no Among 4 - to 6-year -old Vaccine Safety Datalink members, authors  identified \nseizures in the emergency department and hospital from 2000 to 2008 and \noutpatient visits for fever from 2006 to 2008 during days 7 to 10 and 0 to 42 after \nMMRV and MMR + V. Incorporating medical record reviews, we assessed seizure \nrisk after M MRV and MMR + V.  \no From 2006 through 2008, 86 750 children received MMRV; from 2000 through \n2008, 67 438 received same -day MMR + V. Seizures were rare throughout days 0 \nto 42 without peaking during days 7 to 10. There was 1 febrile seizure 7 to 10 \ndays after MMRV and 0 after  MMR + V. Febrile seizure risk was 1 per 86 750 \nMMRV doses (95% confidence interval, 1 per 3 426 441, 1 per 15 570) and 0 per \n67 438 MMR + V doses (1 per 18 282).  \n8 \n \no This study provides reassurance that MMRV and MMR + V were not associated \nwith increased risk of febrile seizures among 4 ‐ to 6‐year ‐olds. We can rule out \nwith 95% confidence a risk greater than 1 febrile seizure per 15 500 MMRV \ndoses and 1 per 18 000 MMR + V doses.  \n• Ma SJ, Xiong YQ, Jiang LN, Chen Q. Risk of febrile seizure after measles -mumps -rubella -\nvaricella vaccine: A systematic review and meta -analysis.  Vaccine . 2015;33(31):3636 -\n3649. doi:10.1016/j.vaccine.2015.06.009  \no PubMed, Embase, BIOSIS Previews, Scopus, Web of Science, Cochrane Library \nand other databases  were searched  through 12 December 2014.  \no A total of thirty -nine studies were included. Thirty -one published or unpublished \nclinical trials involving about 40,000 subjects did not show significant differences \nin incidence of febrile seizure or vaccine related febrile seizure between MMRV \nand MMR w ith or without varicella vaccine after any doses, in the risk windows \nof 0-28, 0 -42 or 0 -56 days and 7 -10 days. In addition, these studies showed that \nthe receipt of concomitant use of MMRV and other pediatric vaccines was not a \nsignificant predictor of fe brile seizure. Eight post -marketing observations \ninvolving more than 3,200,000 subjects were included. No evidence suggested \nelevated risk of febrile seizure associated with MMRV vaccine among children \naged 4 ‐6 years old during 7 ‐10 days or 0 ‐42 days after vaccination. However, an \napproximately 2 ‐fold increase in risk of seizure or febrile seizure during 7 ‐10 \ndays or 5 ‐12 days after MMRV vaccination was found among children aged 10 ‐\n24 months, although the highest incidence of seizure was still lower than \n2.95%. \no First MMRV vaccine dose in children aged 10 -24 months was associated with an \nelevated risk of seizure or febrile seizure.  \nStudies performed outside of the United States  \nCanada  \n• Seo CY , Rashid M, Harris T, Stapleton J, Deeks SL. Assessing safety of Ontario's publicly \nfunded MMR and MMRV immunization programs, 2012 to 2016.  Paediatr Child Health . \n2019;25(6):358 -364. Published 2019 Apr 8. doi:10.1093/pch/pxz037  \no Reports of AEFIs were extracted from the provincial surveillance database on \nMay 9, 2017. Events were grouped by provincial surveillance definitions. \nReporting rates were calculated using provincial population estimates or net \ndoses distributed as the deno minator. A serious AEFI is defined as an AEFI that \nresulted in an in -patient hospitalization or death.  \no  Overall, 289 AEFIs were reported following administration of MMR (n=246) or \nMMRV (n=43) vaccines, for annualized reporting rates of 16.6 and 8.8 reports per \n100,000 distributed doses, respectively. The highest age -specific reporting rate \nwas in children ag ed 1 to 3 years for MMR (7.7 per 100,000 population) and \n9 \n \nchildren aged 4 to 9 years for MMRV (0.8 per 100,000 population). Systemic \nreactions were the most frequently reported event category, while rash was the \nmost frequently reported event for both vaccines. There were 22 serious AEFIs, \n19 following MMR and 3 following MMRV (1.3 and 0.6 per 100,000 doses \ndistributed, respectively).  \no Authors  found a low reporting rate of adverse events following MMR and MMRV \nvaccines in Ontario. No safety concerns were identified.  \nGermany  \n• Schäfer W, Reinders T, Schink T. Second dose of measles -mumps -rubella -varicella vaccine \n(MMRV) and the risk of febrile convulsions.  Vaccine . 2022;40(14):2168 -2172. \ndoi:10.1016/j.vaccine.2022.02.072  \no A retrospective cohort study using claims data from the German \nPharmacoepidemiological Research database (GePaRD) was performed in \nchildren born between January 1st, 2004 and October 31st, 2015 who received \ntwo doses of MMRV, MMR  + V or MMR. Cases were defi ned as hospitalization \nwith a diagnosis of febrile convulsions ( FC) without neurological conditions coded \nas main discharge diagnosis. Unadjusted and adjusted odds ratios (OR) with 95% \nconfidence inte rvals (CIs) were calculated to compare the risk of FC. Stratified \nanalyses were performed to examine potential effect modification by age, sex, \nhistory of FC or type of first dose vaccine.  \no In the first 30  days after second dose  vaccination , 464 FCs were observed in a \ncohort of 528,639 children with a median age of 17  months. After adjustment for \npotential confounders, the adjusted OR for FC in the 30  days after vaccination \nwas 1.25 (95% CI 0.67 –2.30) for MMRV compared to MMR  + V and 1.04 (0 .82–\n1.32) for MMRV compared to MMR. History of FC was the most important risk \nfactor with an OR of 36.26 (29.30 –44.89). We found no effect modification by \nage, sex, history of FC, or type of first dose vaccine.  \no Author’s conclusions: Use of MMRV at second dose is not associated with an \nincreased risk of FC compared to MMR  + V or MMR, irrespective of age, sex, \nhistory of FC, or type of first dose vaccine.  \nItaly  \n• Stefanizzi P , Stella P , Ancona D, et al. Adverse Events Following Measles -Mumps -Rubella -\nVaricella Vaccination and the Case of Seizures: A Post Marketing Active Surveillance in \nPuglia Italian Region, 2017 -2018.  Vaccines (Basel) . 2019;7(4):140. Published 2019 Oct 7. \ndoi:10.3390/vaccines7040140  \no In the Puglia Region launched, from May 2017 to November 2018, a post -\nmarketing active surveillance program of adverse events following MMRV \nimmunization (AEFIs). Immunized children (second year of life) were enrolled on \n10 \n \na voluntary basis, AEFIs diaries were used, and their parents were interviewed 25 \ndays after the immunization.  \no There were 2540 children enrolled; 2149/2540 (84.6%) completed the post -\nvaccination follow -up. Of these, 992 AEFIs were registered with a reporting rate \nof 46.2 × 100 doses: 883/992 (89.0%) AEFIs were not serious, while 109/992 \n(11.0%) were serious. For se rious AEFIs, the evaluation of causality assessment \nwas performed using the algorithm proposed by the World Health Organisation \n(WHO): 82/109 consistent causal associations to MMRV immunization were \ndetected (reporting rate of consistent AEFIs: 3.8 × 100 f ollow -up). All serious \nAEFIs consistently associated with immunization resulted completely resolved at \nthe follow -up. The reporting rate of seizure consistently associated with \nimmunization was 0.05 × 100, lower than data previous published in the \nliteratu re that did not report the causality assessment.  \no Author’s conclusion: Because  no emerging signals were detected, data from the \nactive surveillance program confirmed the safety profile of the MMRV vaccine.  \nClinical Trial data  \n• Reisinger KS, Brown ML, Xu J, et al. A combination measles, mumps, rubella, and varicella \nvaccine (ProQuad) given to 4 - to 6-year-old healthy children vaccinated previously with M -\nM-RII and Varivax [published correction appears in Pediatrics. 2006 \nJun;117(6):2338].  Pediatrics . 2006;117(2):265 -272. doi:10.1542/peds.2005 -0092  \no Four- to 6-year-old children who had been immunized previously with M -M-RII and \nVarivax were assigned randomly to receive either ProQuad and placebo ( N = 399), M -\nM-RII and placebo ( N = 195), or M -M-RII and Varivax ( N = 205) and were then \nmonitored for safety and immunogenicity.  ProQuad was generally well tolerated.  \nSimilarity (noninferiority) was demonstrated in postvaccination antibody responses \nto measles, mumps, and rubella between recipients of ProQuad and all recipients \nof M-M-RII and in responses to varicella between recipients of ProQuad and \nrecipients of Var ivax. Postvaccination seropositivity rates for antibodies against all 4 \nviruses were nearly 100% in all 3 groups. Small fold increases were observed for \nmeasles, mumps, and rubella antibody titers. In contrast, substantial boosts in \nvaricella antibody titers were observed among recipients of a second dose of \nvaricella vaccine, administered as ProQuad or Varivax.  \no ProQuad may be used in place of a second dose of M -M-RII or second doses of M -\nM-RII and Varivax for 4 - to 6-year-old children.  \n• Shinefield H, Black S, Thear M, et al. Safety and immunogenicity of a measles, mumps, \nrubella and varicella vaccine given with combined Haemophilus influenzae type b \nconjugate/hepatitis B vaccines and combined diphtheria -tetanus -acellular pertussis \nvaccine s. Pediatr Infect Dis J . 2006;25(4):287 -292. \ndoi:10.1097/01.inf.0000207857.10947.1f  \no In this open, multicenter trial, 1915 healthy children ages 12 -15 months were \nrandomized into 3 groups: group 1, MMRV, combined Haemophilus influenzae \n11 \n \ntype b conjugate -hepatitis B vaccines (Hib/HepB) and combined diphtheria -\ntetanus -acellular pertussis vaccines (DTaP) concomitantly; group 2, MMRV \nfollowed by Hib/HepB and DTaP 42 days later; group 3, MMR and varicella \nvaccine followed by Hib/HepB and DTaP 42 days later.  \no Antibody responses to measles, mumps, rubella, varicella, Hib, HepB, diphtheria \nand tetanus were similar between groups 1 and 2 (all >95%, except varicella, \n89.7% in group 1 and 90.9% in group 2). Pertussis toxin and filamentous \nhemagglutinin responses wer e significantly lower in group 1 than in group 2 \n(group 1, 74.1 and 67.1%; group 2, 90.4 and 86.8%, respectively). An exploratory \nanalysis suggested that the difference in pertussis toxin and filamentous \nhemagglutinin responses was likely the result of stu dy design rather than \ninterference among vaccine components because the groups differed in age of \nreceipt of DTaP (group 1, approximately 12 months; group 2, approximately 13.5 \nmonths). When the groups were matched for age, sample size was sufficient for \ncomparison only in children > or =13.5 months old. Pertussis toxin and \nfilamentous hemagglutinin responses were similar in these children. The safety \nprofiles for each vaccination regimen were comparable.  \no Concomitant administration of MMRV, Hib/HepB and DTaP is well -tolerated.  \n• Leonardi M, Bromberg K, Baxter R, et al. Immunogenicity and safety of MMRV and PCV -7 \nadministered concomitantly in healthy children.  Pediatrics . 2011;128(6):e1387 -e1394. \ndoi:10.1542/peds.2010 -2132  \no Healthy 12 - to 15 -month -old children who lacked vaccination and clinical \nhistories for measles, mumps, rubella, varicella, and zoster but had written \ndocumentation of receipt of a 3 -dose primary series of PCV -7 were randomly \nassigned in a 2:1:1 ratio to re ceive either the MMRV and PCV -7 (group 1), PCV -7 \nfollowed 6 weeks later by MMRV (group 2), or MMRV followed 6 weeks later by \nPCV-7 (group 3). The primary safety analysis was 56 days (28 days after each \nvisit). Immunogenicity was evaluated 6 weeks after eac h vaccination.  \no A total of 1027 children were enrolled (group 1: 510; group 2: 258; group 3: 259). \nFor all 3 groups, the antibody response rate was ≥96.8% for measles, mumps, \nand rubella, ≥88.0% for varicella -zoster virus, and ≥98.3% for all of the 7 \nStreptococcus pneumon iae serotypes. The immune responses to all antigens \npresent in MMRV and PCV -7 were similar whether administered concomitantly \nor sequentially. The incidence of local and systemic adverse experiences (AEs) \nwas comparable between group 1 and groups 2 and 3 c ombined. No vaccine ‐\nrelated serious AEs were reported.  \no Concomitant administration of the MMRV and PCV -7 is highly immunogenic and \ngenerally well tolerated . Similar immune responses between the groups support \nconcomitant administration of the MMRV and PCV -7 to healthy children 12 to 15 \nmonths of age.  \n12 \n \n• Klein NP , Shepard J, Bedell L, Odrljin T, Dull P . Immunogenicity and safety of a \nquadrivalent meningococcal conjugate vaccine administered concomitantly with \nmeasles, mumps, rubella, varicella vaccine in healthy toddlers.  Vaccine . \n2012;30(26):3929 -3936. doi:10.1016/j.vaccine.2012.03.080  \no Should be noted that for this study, because of a shortage of Pro Quad during \npart of the study, MMR+V was used.  When “MMRV” is used in this paper, it \nincludes subjects vaccinated with MMRV or MMR+V.  \no Two age groups were concurrently enrolled: 7 - to 9-month -old infants who \nreceived 2 doses of MenACWY -CRM at 7 -9 and 12 months and were randomized \n1:1 to receive MenACWY -CRM with or without MMRV at 12 months, and 12 -\nmonth -old infants who received MMRV only at 12 months. Using predefined \nnon-inferiority criteria, immune responses to the antigens in MMRV were \ncompared between those who did and did not receive MenACWY -CRM; immune \nresponses to MenACWY -CRM as measured by the percentage of subjects with \nhuman seru m bactericidal activity (hSBA) titers ≥ 8, were compared between \nthose who did and did not receive concomitant MMRV. Adequacy of the immune \nresponse to 2 doses of MenACWY -CRM administered at 7 -9 and 12 months was \nalso assessed. Local and systemic reactions , adverse events resulting in \nwithdrawal or requiring medical attention and serious adverse events were \nmonitored.  \no Concomitant administration of MMRV with MenACWY -CRM did not affect the \nimmune response to either vaccine. The 2 -dose series of MenACWY -CRM \ninduced adequate immune response to all 4 serogroups. No increased \nreactogenicity was observed with MenACWY ‐CRM+MMRV compared with \nMMRV alone, and there were no study ‐related serious adverse events.  \no Concomitant administration of MenACWY -CRM with MMRV vaccinations at 12 \nmonths was well -tolerated, without safety concerns. Robust immune responses \nto all components of both vaccines were produced and all criteria for non -\ninferiority were met, supporting th e use of a 2 -dose regimen of MenACWY -CRM \nin this age group.", "summary": "1    MMRV Vaccine Safety     Contents   Summary  ................................ ................................ ................................ ................................ ......  1  Cochrane Review  ................................ ................................ ................................ ...........................  2  General safety  ................................ ................................ ................................ ...............................  3  Febrile…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-25-26-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-06-25-26/01-MMRV-safety-summary-508.pdf", "doc_date": "2025-06-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 12}
{"title": "01 kulldorff MMRV 508", "content": "MMRV\nMMRV = One combined shot for Measles, Mumps, \nRubella and Varicella \nalternative to\nMMR+V = Two shots, one for Measles, Mumps and \nRubella and another for Varicella\nNo known difference in efficacy\n \nMMRV Timeline\n2005: FDA licensed the combined MMRV \nvaccine for use in children 12 months to 12 \nyears of age.\n2006: The CDC Advisory Committee on  \nImmunization Practices recommended use of \nMMRV, with preference over separate MMR \nand Varicella vaccines.\n \n\nWeekly Safety Surveillance\nCDC’s Vaccine Safety Datalink Rapid Cycle \nAnalysis\nWeekly Data from Electronic Health Records\nFirst MMRV dose, at age 12 -23 months\n2007: Signal for an excess number of febrile \nseizures after ~26,000 doses \n \nSeizure Signal\nFor 12 -23 month olds, \nseizure signal on February \n11, 2007. \nCumulative doses at that \ntime: 25,779\nObserved Expected Relative \nRiskLLR (critical \nvalue)\nNumber \nSeizures 59 38 1.57 5.17 (4.12)\nNote: No seizure risk after second dose at age 4 -6 years old \n\nPostvaccination seizures among 12 - to 23 -month -olds according \nto vaccine received: VSD study population, 2000 –2008.\n\nRisk for Febrile Seizures after \nMMRV Compared to MMR+V\n\nAlso excess in post -vaccination fever\n\nMMRV Working Group Vote\nFour Options for the Vote, ages 12 -47 months:\n1.Both recommended, Preference for MMRV\n2.Both recommended, Equal preference\n3.Both recommended, Preference for MMR+V\n4.Only recommend MMR+V1. Zero votes\n2. Minority\n3. Majority\n4. One vote\n2009\nACIP Vote\nFour Options for the Vote, ages 12 -47 months:\n1.Both recommended, Preference for MMRV\n2.Both recommended, Equal preference\n3.Recommend both, Preference for MMR+V\n4.Only recommend MMR+V1. Zero votes\n2. Majority\n3. Minority\n4. Zero votesJune 2009\n\nCDC 2009 Recommendation\nACIP is only advisory. CDC decided:\n-Either MMRV or MMR+V may be \nadministered\n-For dose 1 in children age 12 -47 months, \npreference for MMR+V\n\nSummary\n-No known difference in efficacy between \nMMRV and MMR+V\n-After first dose for children at ages 12 -23 \nmonths, more febrile seizures after MMRV \nthan MMR+V, ~ 1 per 2,300 doses\n-After second dose at ages 4 -6 years, no \nexcess risk for febrile seizures\nProposed Recommendation\nAs there exist a safer equally effective \nalternative, the MMRV vaccine should \nnot be administered to children under \nthe age of 47 months.", "summary": "MMRV MMRV = One combined shot for Measles, Mumps,  Rubella and Varicella  alternative to MMR+V = Two shots, one for Measles, Mumps and  Rubella and another for Varicella No known difference in efficacy   MMRV Timeline 2005: FDA licensed the combined MMRV  vaccine for use in children 12 months to 12  years of age. 2006: The CDC Advisory Committee on   Immunization Practices recommended use of  MMRV, with preference over separate MMR  and Varicella vaccines.    Weekly Safety Surveillance CDC’s…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-25-26-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-06-25-26/01-kulldorff-MMRV-508.pdf", "doc_date": "2025-06-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 13}
{"title": "01 minhaj Mpox 508", "content": "Agency for Toxic Substances and Disease Registry National Center for Environmental Health \nCenters for Disease Control and Prevention \nMpox Vaccine Work Group \nFaisal Syed Minhaj, PharmD, MPH Poxvirus and Rabies Branch Centers for Disease Control and Prevention \nACIP Meeting April 15, 2025 \n•Genus: Orthopoxvirus \n•Family: Poxviridae \n•Discovered in 1958 after two pox-like disease outbreaks in research monkey colonies \n•Specific animal reservoir unknown, but likely African small mammals \n•On November 28, 2022, WHO implemented the preferred term “mpox” for the disease \n•Two clades of MPXV: \n-Clade I: found in central Africa and historically associated with greater disease severity in a higher proportion of people \n-Clade II: found in West Africa and caused the 2022 global outbreak Monkeypox virus (MPXV) \n\nMpox historical context \nMpox historical context \nMpox historical context \nMpox historical context \nMpox historical context \n• First case in this outbreak identified in the Unite d Kingdom in May 2022 \n• Primarily affecting gay, bisexual, and other men wh o have sex with men (MSM) \n• Associated with person-to-person spread via close s kin-to-skin contact including \nsex \n• Deaths have occurred, primarily among persons with severe immunocompromise \nfrom advanced HIV \n• U.S. case counts and deaths comprise 1/3 of cases a nd deaths globally \n- >30,000 cases \n- >60 deaths Global Mpox Outbreak, 2022 \nUnited States mpox case count and 7-day moving Average – May 2022 through March 2025 \nPeak Confirmed Daily Cases (7-day average): 467 cases \nDate \nUnited States mpox case count and 7-day moving Average – August 2024 through March 2025 \nSubject to reporting delays \nThe currentmedian 7-\ndaymovingaverage for confirmedcases for February is 3.3-1.2per day.\n•ACIP recommends the 2-dose* JYNNEOS vaccine series fo r persons aged 18 \nyears and older at risk of mpox during an mpox outbrea k §.\n*Dose 2 administered one month after dose 1 §Public health authorities determine whether there i s an mpox outbreak; a \nsingle case may be considered an mpox outbreak at t he discretion of public \nhealth authorities. Other circumstances in which a public health response may \nbe indicated include ongoing risk of introduction o f mpox into a community \ndue to disease activity in another geographic area.Current Recommendation (voted February 2023) \nACIP recommends vaccination* with the 2-dose †JYNNEOS vaccine series for \npersons aged 18 years and older at risk for mpox §?Current Recommendation (voted October 2023) –updated language \n*Interim recommendation to be revisited in 2-3 year s \n† Dose 2 administered 28 days after dose 1 \n§Persons at risk: \n1. Gay, bisexual, and other men who have sex with m en (MSM), or a person who has sex with \nMSM who in the past 6 months have had one of the follow ing: \n•A new diagnosis of ≥ 1 sexually transmitted disease  \n•More than one sex partner \n•Sex at a commercial sex venue \n•Sex in association with a large public event in a g eographic area where mpox \ntransmission is occurring \n2. Sexual partners of persons with the risks descri bed in above \n3. Persons who anticipate experiencing any of the a bove \nMpox current situation \n•Modeling data suggests any increase in coverage reduces the risk of \noutbreaks, and low coverage (<50%) could promote la rger outbreaks Jynneos vaccine coverage in the United States among  people \nat risk for mpox – June 2022 to September 2024 \nOverall vaccine coverage \n1-dose: 42.2% and 2-dose: 26.2 % \nU.S. mpox case trends in adolescents and pediatrics , \nMay 2022 – March 2025 \nCase \nCount Age \ngroup \n92 12-17 \n17 6-11 \n23 1-5\n15 <1 \n147 Total \nSubject to reporting delays \n•Previously, there was no data evaluating Jynneos in childr en <18 years \n•An NIH sponsored trial completed last year evaluating Jyn neos in 12–17-\nyear-old adolescents \n-DMID 22-0020: A Phase 2 Randomized, Open-Label Mult isite Trial to Inform \nPublic Health Strategies Involving Use of MVA-BN Va ccine for Mpox (DoSES) \n•Stage 2: non-inferiority trial of Jynneos in adoles cents compared to adults \n•Proposed recommendations would extend current recommendations to \n12–17-year-old adolescents New data on safety and immunogenicity in adolescents \n•ACIP recommends the 2-dose* JYNNEOS vaccine series fo r persons 12–17 \nyears of age at risk of mpox during an mpox outbreak §.\n*Dose 2 administered one month after dose 1 §Public health authorities determine whether there i s an mpox outbreak; a \nsingle case may be considered an mpox outbreak at t he discretion of public \nhealth authorities. Other circumstances in which a public health response may \nbe indicated include ongoing risk of introduction o f mpox into a community \ndue to disease activity in another geographic area.Proposed Recommendation 1 \nACIP recommends vaccination* with the 2-dose †JYNNEOS vaccine series for \npersons aged 12–17 years at risk for mpox §?Proposed Recommendation 2 \n*Interim recommendation to be revisited in 2-3 year s \n† Dose 2 administered 28 days after dose 1 \n§Persons at risk: \n1. Gay, bisexual, and other men who have sex with m en (MSM), or a person who has sex with \nMSM who in the past 6 months have had one of the fo llowing: \n•A new diagnosis of ≥ 1 sexually transmitted disease  \n•More than one sex partner \n•Sex at a commercial sex venue \n•Sex in association with a large public event in a g eographic area where mpox \ntransmission is occurring \n2. Sexual partners of persons with the risks descri bed in above \n3. Persons who anticipate experiencing any of the a bove \n•Presentation of the safety and immunogenicity of Jynneo s in 12–17-year-\nolds: Dr. C. Buddy Creech \n•Evidence to recommendations framework: \n-Outbreak recommendations: Dr. Faisal Minhaj \n-Routine recommendations: Dr. Faisal Minhaj Goals for today’s meeting \nTentative timeline for ACIP discussions and votes \nACIP Meeting: \nPresentation \nof two EtR \nApril 2025 ACIP Meeting: \nVoting on two \nEtR \nJune 2025 Continue monitoring \nmpox epidemiology \nand vaccine \nrecommendations \nOngoing \n•WG Chair \n-Yvonne (Bonnie) Maldonado \n•WG Lead \n-Faisal Syed Minhaj \n•ACIP Members \n-Edwin Asturias \n-Lin Chen \n•Ex Officio/Liaison members \n-CSTE: Paul Cieslak \n-ASTHO: Chris Taylor \n-NACHO: Philip Huang \n-FDA: Sixun Yang, Pete Weina \n-ACOG: Howard Minkoff \n-AAP: Jim Campbell WG Composition \n•Ex Officio/Liaison members (cont.) \n-HRSA: Vikram Krishnasamy \n-AIM: Heather Roth \n-NIH: Kimberly Taylor \n-IHS: Uzo Chukwama \n-NACI: Nicole Forbes, Joshua Montroy \n-IDSA: Shireesha Dhanireddy, Katherine Hsu \n•Invited Consultants \n-Inger Damon \n-Stuart Isaacs \n-Mike Merchlinsky \n-Amanda Zarrabian •Clinician experts \nSTIs, HIV, mpox, pediatrics \n-Jason Zucker \n-Kim Workowski \n-Pablo Sánchez \n-Beth Bell \nImmunization \n-Ruth Karron \n-Flor Munoz-Rivas \nCDC Contributors \n•Mpox Epi/Lab/Vaccine experts \n-Agam Rao \n-Andrea McCollum \n-Christina Hutson \n-Sathesh Panayampalli \n-Shama Cash-Goldwasser \n•Vaccine Safety \n-Michael McNeil \n-Jonathan Duffy •Regulatory Affairs \n-Yon Yu \n•STIs and HIV \n-Laura Bachman \n-Jesse O’Shea \n•Drug Services \n-Julian Jolly \n•Vaccine Implementation \n-Liz Velazquez \nFor more information, contact CDC 1-800-CDC-INFO (232-4636) TTY:  1-888-232-6348    www.cdc.gov The findings and conclusions in this report are tho se of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Pre vention. \nThank you", "summary": "Agency for Toxic Substances and Disease Registry National Center for Environmental Health  Centers for Disease Control and Prevention  Mpox Vaccine Work Group  Faisal Syed Minhaj, PharmD, MPH Poxvirus and Rabies Branch Centers for Disease Control and Prevention  ACIP Meeting April 15, 2025  •Genus: Orthopoxvirus  •Family: Poxviridae  •Discovered in 1958 after two pox-like disease outbreaks in research monkey colonies  •Specific animal reservoir unknown, but likely African small mammals  •On…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/01-minhaj-Mpox-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 23}
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\"#\u001e\" $%$& '\u001f \u001d\u001e \u001f ( )  \u001d * +,-  ., / \u001f \u001d\u001e \u001f 0 * \u001d &/ ( $  , / \u001f \u001d\u001e \u001f 1 2 3 $& ' 4 &$)5 6\u001f \u001d\u001e \u001f -.  &2) 4 &$/ \u001f \u001d\u001e \u001f 7$ 88 &$/ - *9 \u0005\u0014 \u0011 \u0005\u0014 \t  \u000b \t \u0019\u0018\u000b \t \u0000\u0001 \u0004\b \f\b\u0017 :\u0004;\u0002 \t  \u000b \t  \u0019\u001a \t \u000b\b\u001c \u0001\u0003<\u0001 \r \u0011 \u0005\u0014 \u0012\u0001 \u0002 \t  \u000b \t \u0013\u0016\u0004\b\u0002 \u0000\u0001 \u0015\u0015 \u0012 \u0005 \t  \u000b \t \f\u0016 \u0003\u0001 \u0015 \u0018 \u000e  \b\u0014 \u0015 \u0001 \u0002 \t  \u000b \t \f\b\u0004;\u0002= \u0005> \u0012\b\u0002 \u0003 \t  \u000b \t  ?\u0003 \t @\b\u0017 \u0018 \b\u0014; \u0016 \u0012\b A\u0001: ;\u0002;\r;\u0010; \u0016 \u0012 ; \u0016 \t  \u000b \t \u0019\b\u0016 \u0012\u0001 \u0002\b B \u000e \u001b \u0005 \u0011 ;…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/02-Creech-Mpox-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 26}
{"title": "03 minhaj Mpox 508", "content": "Agency for Toxic Substances and Disease Registry National Center for Environmental Health \nCenters for Disease Control and Prevention \nEvidence to Recommendations Framework: Vaccination with Jynneos for Adolescents at Risk of  \nMpox During Outbreaks \nFaisal Syed Minhaj, PharmD, MPH Poxvirus and Rabies Branch Centers for Disease Control and Prevention Advisory Committee on Immunization Practices April 15, 2025 \n•Structure to describe information considering in moving fr om evidence to \nACIP vaccine recommendations \n•Provides transparency around the impact of additional fa ctors on \ndeliberations when considering a recommendation Evidence to Recommendations (EtR) Framework \n•Does ACIP recommend the 2-dose* JYNNEOS vaccine serie s for persons 12–\n17 years of age at risk of mpox during an mpox outbre ak §?\n*Dose 2 administered one month after dose 1 §Public health authorities determine whether there is an mpox outbreak; a single case may be \nconsidered an mpox outbreak at the discretion of pu blic health authorities. Other circumstances \nin which a public health response may be indicated include ongoing risk of introduction of mpox \ninto a community due to disease activity in another  geographic area. EtR question \nEvidence to Recommendation Domains \nQuestion(s) EtR Domain \n•Is the problem of public health importance? Public Health Problem \n•How substantial are the desirable anticipated effec ts? \n•How substantial are the undesirable anticipated eff ects? \n•Do the desirable effects outweigh the undesirable e ffects? Benefits and Harms \n•Does the target population feel the desirable effec ts are large relative to the \nundesirable effects? \n•Is there important uncertainty or variability in ho w much people value the \nmain outcome? Values \n•Is the intervention acceptable to key stakeholders? Acceptability \n•What would be the impact on health equity? Equity \n•Is the intervention feasible to implement? Feasibility \n•Is the intervention a reasonable and efficient allo cation of resources? Resource Use \nEtR Domain: Public Health Problem \nMpox current situation \nGlobal distribution of confirmed mpox cases, January 1, 2024 – March 26, 2025 \n\nGlobal distribution of confirmed clade I mpox casesJanuary 1, 2024 – April 13, 2025 \n\nUnited States mpox case count and 7-day moving Average – May 2022 through March 2025 \nPeak Confirmed Daily Cases (7-day average): 467 cases \nU.S. mpox case counts in pediatrics, May 2022 \nthrough March 2025 \nCase Count Age \ngroup \n92 12-17 \n17 6-11 \n23 1-5\n15 <1 \n147 Total \n\nTypical mpox manifestations \n\nSevere manifestations of mpox \nKeratitis and conjunctival ulcer \nT-wave inversions in inferior and anterolateral lea ds of a patient \nwith mpox with elevated Tn, SOB, decreased exercise  tolerance Encephalomyelitis in a patient with mpox \nSevere manifestations from uncontrolled viral replication in severely immunocompromised \nCarrubba S. Lancet Infect Dis. 2023 May;23(5):e190-e 197. \nMitjà O. Lancet. 2023 Mar 18;401(10380):939-949. \n\nAre outbreaks of mpox of public health importance? \nNo Probably no Uncertain Yes \nVaries \nProbably Yes \nEtR Domain: Benefits and Harms \n•Adolescent arm met pre-specified criteria for non-inferior ity \n-GMT ratio of adolescents to adults was 1.60 (CI 1.3 2, 1.95) \n•Vaccine was safe and well tolerated in adolescents \n-Solicited systemic and local AEs were similar betwe en adolescents and adults \n•Systemic: 74% (CI 69, 79) vs 73% (CI 66, 79) \n•Local: 88% (CI 84, 91) vs 91% (CI 87,95) \n-Unsolicited related AEs: mainly injection site rela ted \n-Dizziness in adolescents is common with vaccine adm inistration in this age group \nand is not likely to represent a safety concern Adolescent safety and immunogenicity study summary \n•Vaccine Adverse Event Reporting System (VAERS) \n-National passive reporting system \n•Vaccine Safety Datalink (VSD) \n-Large linked healthcare data \n•V-safe \n-Web-based survey of vaccinees \n•Single-patient Emergency Investigational New Drug ( EIND) procedures \n-EIND provided vaccine access for individuals <18 ye ars of age prior to EUA \n-Collected adverse event information from the vaccin ation provider 28 days after \neach dose CDC’s vaccine safety data sources for JYNNEOS \n•Vaccine adverse event reporting system (VAERS) 1\n-At least 1,245 vaccinees nationwide \n-One report of syncope \n-Three reports of unspecified mild local and systemi c reactions \n•VSD 2\n-88 vaccinees \n-No adverse events of special interest observed \n•V-safe 1\n-No participants were <18 years of age \n•EIND 3\n-57 vaccinees \n-21% reported local or systemic reactions. No seriou s adverse events were reported Adverse events among individuals <18 years of age 2022–2023 \n1) https://pubmed.ncbi.nlm.nih.gov/38647241/ 2) htt ps://pubmed.ncbi.nlm.nih.gov/39565485/ 3) https://p ubmed.ncbi.nlm.nih.gov/36480476/ \nHow substantial are the desirable anticipated effects \nMinimal Small Moderate Large \nDon’t Know Varies \n\nHow substantial are the undesirable anticipated effects \nMinimal Small Moderate Large \nDon’t Know Varies \n\nDo the desirable effects outweigh the undesirable ef fects? \nFavors Intervention Favors Comparison Favors Both \nFavors Neither Unclear \n\nEtR Domain: Values \n•NIH rapidly completed trial recruitment \n•Participants were supportive in participating to help frien ds \n•When an outbreak occurred (i.e., 2022 global outbreak) , pediatric close \ncontacts were vaccinated \n•Adolescent Medicine Trials Network for HIV/AIDS Intervent ions (ATN) \nyouth advisors were surveyed and 12/13 respondents we re supportive of \nvaccination \n•We do not know what type of outbreak would occur in t he future, and how \nadolescents would perceive their risk or acceptability of vaccine Values Considerations \nJYNNEOS first doses administered to children 17 yea rs \nand younger by sex May 2022 – September 2024 \nPersons with no age data available were removed fro m the analysis Total first doses Age group \n798 12-17 \n391 6-11 \n293 1-5\n150 <1 \n1,632 Total \nDoes the target population feel that the desirable effects are large relative to the undesirable effec ts? \nNo Probably no Uncertain Yes \nVaries \nProbably Yes \nIs there important uncertainty about or variability  in \nhow much people value the main outcomes? \nImportant uncertainty or variability Possibly important uncertainty or variability \nNo known undesirable outcomes \nProbably no important uncertainty or variability No important uncertainty or variability \nEtR Domain: Acceptability \nData available for acceptability domain \nSurvey administered to \nAdolescent Medicine Trials \nNetwork (ATN) providers Survey of mothers of \nadolescents and younger \nchildren \nData available for acceptability domain \nSurvey administered to \nAdolescent Medicine Trials \nNetwork (ATN) providers Survey of mothers of \nadolescents and younger \nchildren \n\nATN V Sites \nEastern U.S. \nNew Orleans, Louisiana \nTulane University Adolescent Medicine \nAtlanta, Georgia \nEmory University \nSan Francisco, California \nBridge HIV, San Francisco Department of Public Health \nLos Angeles, California \nChildren’s Hospital Los Angeles Southern U.S. \nNew York City, New York \nCallen -Lorde Community \nHealth Center Washington, D.C. \nChildren’s National Hospital Boston, Massachusetts \nThe Fenway Institute Houston, Texas \nBaylor College of Medicine/ Texas Children’s Hospital Tampa, Florida \nUniversity of South Florida \nMemphis, Tennessee \nSt. Jude Children’s Research Hospital Western & Midwestern U.S. \nChicago, Illinois \nAdolescent and Young Adult Research (AWAR) @ The CORE Center \n•Distributed to clinicians for 1 week in January 2025 \n•23 providers responded \n-21 (91%) treat 12–17-year-olds at risk for mpox \n•Among those 21 providers: \n-17 (81%) offer vaccines in clinic; 11 (52%) offer mpox vaccine. \n-Type of practice: \no19 (90%) university-based; \no1 (5%) FQHC; \no3 (14%) community-based. Survey to Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) providers \nN = 21 \nn (%) Provider Characteristics Provider type \n16 (76) Physician \n5 (24) NP/PA \nSpecialty \n10 (48) Adolescent medicine \n3 (14) Pediatrics \n3 (14) Medicine and pediatrics \n3 (14) Family medicine \n1 (5) Internal medicine \n1 (5) Pediatric ID \nSurvey to ATN providers (N = 21) \nIf CDC recommended the mpox vaccine for 12–17-year-o lds with risk \nfactors, would you recommend it for eligible patien ts? \n20 1\nYes \nNo NP/PA, family medicine \nWhat are your concerns about recommending mpox vacc ine for your \neligible 12–17-year-old patients? Survey to ATN providers (N = 21) \n20 1\nI have no concerns. \nI have concerns. “I am not sure if it is effective in preventing mpox” \nWhat are challenges associated with offering the mp ox vaccine in your practice?Survey to ATN providers (N = 21) \nN = 21 \nn (%) Statement \n5 (24) There are no challenges in my practice \n16 (76) There are challenges \n7 (33) It is costly for the clinic to stock \n5 (24) Patients are unfamiliar with mpox vaccine \n4 (19) I do not know if there are challenges \n3 (14) It is costly for patients \n2 (10) I do not know how to access mpox vaccine \n1 (5) I do not have enough staff trained to administer th is vaccine \n1 (5) I am unfamiliar with mpox \n1 (5) I am unfamiliar with mpox vaccine \n1 (5) Other \nData available for acceptability domain \nSurvey administered to \nAdolescent Medicine Trials \nNetwork (ATN) providers Survey of mothers of \nadolescents and younger \nchildren \n\n•Total surveyed: 566 \n•Unclear the age of all children of the mothers \n-Oldest child mean age 9.6 (SD 4.8) \n-43% of the population had their oldest child age between 12-17 years \n•Timeframe: July 2022 \n•Variety of household incomes were represented Online survey of Mothers with children ≤18 years \nLiu S, Chu H. Patient Educ Couns. 2023 Sep;114:1078 42. \nn (%) Variable \n510 (90) Receipt of all or some CDC recommended immunizations Race/Ethnicity \n59 (10) Black \n40 (7.1) Hispanic \n19 (3.4) Asian/NHOPI/Native American \n439 (78) White \n9 (1.6) Other \nNumber of children \n238 (42) One \n205 (36) Two \n78 (14) Three \n45 (8.0) More than three \n$150,000 or more $100,000 -$149,999 $75,000 -$99,999 $50,000 -$74,999 $35,000 -$49,999 $25,000 -$34,999 $15,000 -$24,999 Below $15,000 \n62 81 105 119 66 70 39 24 \nLiu S, Chu H. Patient Educ Couns. 2023 Sep;114:1078 42. 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% It is likely that my children will get mpox My children are at risk of getting mpox It is possible that my children will get mpox \nStrongly disagree Disagree Neither agree nor disagree Agree Strongly Agree Low belief that children were at risk of getting mp ox \nSome agreement that vaccination will impact disease\nLiu S, Chu H. Patient Educ Couns. 2023 Sep;114:1078 42. 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Mpox vaccine will work in preventing disease If my children get the vaccine, they will be less \nlikely to get mpox \nStrongly disagree Disagree Neither agree nor disagree Agree Strongly Agree \n•Asked “what is the likelihood that you will”: Likelihood to vaccinate is numerically low, but hig her \nthan expected \nLiu S, Chu H. Patient Educ Couns. 2023 Sep;114:1078 42. 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Consider getting an mpox vaccine for your children Try to get an mpox vaccine for your children Actually get your children an mpox vaccine \nVery unlikely Unlikely Neutral Likely Very Likely \n•Mothers from the survey do not view their children at r isk for mpox. \n-However, the intent to vaccinate is higher than exp ected. \n•Vaccines were primarily given to adolescents both through  public health \nand STI clinics. \n•Among 21 surveyed ATN providers who provide care for at-risk adolescents: \n-Over half already offer the mpox vaccine. \n-95% would recommend mpox vaccines for eligible pati ents and do not have \nconcerns about recommending the vaccine. \n-Majority expressed challenges associated with offer ing the vaccine; most \ncommon concern was financial cost to the clinic. Summary of Acceptability data \nIs the intervention acceptable to key stakeholders?\nNo Probably no Uncertain Yes \nVaries \nProbably Yes \nEtR Domain: Health Equity \nVaccine administrations* and cases in adolescents by  \nrace and ethnicity, May 2022 – March 2025 \nn=92 n=798 \n*Vaccine administration through September 2024 Case dat a \nthrough March 2025 +Includes 3 mpox cases indicating Multiple races. Mul tiple \nraces was not reported for vaccine administration da ta. \nIf Hispanic or Latino was indicated for ethnicity, Race/ethnicity is indicated as Hispanic or Latino; if Hispanic or \nLatino ethnicity was not indicated, Race/ethnicity is indicated \nas Race Vaccine Administrations Mpox Cases \n+\n•No groups or settings would be disadvantaged by recomm endation for \nJYNNEOS use during mpox outbreaks. \n•Immunogenicity is the same for immunocompetent persons 12-17 years. \n•Implementation of vaccine should assure equitable access.\n•Endorsement by ACIP could facilitate broad acceptance o f recommendation \n(e.g., insurance, health departments, pharmacies). Health Equity \nWhat would be the impact on health equity? \nReduced Probably Reduced Probably no impact Increased \nVaries \nProbably Increased \nDon’t know \n\nEtR Domain: Feasibility \n•Wide range of vaccinators can administer vaccine (e.g., pediatricians, \npharmacists, public health nurses) \n•Wide range of potential facilities: public health, STI clinic, a dolescent health \nclinic, pediatrician offices \n•Same Immunization Information Systems (IIS) requirement s and reporting \ninfrastructure as other vaccines \n•Limitations to access \n-Poor access in rural communities \n-Cost of vaccine and 10 vial minimum ordering quanti ty could hinder practices \nstocking vaccine \n-Pediatricians may defer to STI/adolescent clinics Feasibility Considerations \n•Two doses, 28 days apart requires follow up and reminde rs \n•JYNNEOS, once thawed/refrigerated, is good for either 4 or 8 weeks, \nallowing some time to schedule a second dose. \n•Frozen storage is ~18 months Feasibility considerations (cont.) \nIs the intervention feasible to implement? \nNo Probably no Uncertain Yes \nVaries \nProbably Yes \nEtR Domain: Resource Use \n•JYNNEOS is commercially available \n-Similar mechanisms for billing/reimbursement \n•Medicaid/Medicare/317 funding \n-Requires similar resources to other vaccine outbrea k responses \n•Generally, vaccines are a good use of resources during an outbreak \n•Cost-effectiveness of vaccination during a future outbr eak in adolescents is \nuncertain Resource Use \nIs the intervention a reasonable and efficient allocation of resources? \nNo Probably no Uncertain Yes \nVaries \nProbably Yes \nBalance of Consequences \nSummary of Work Group Interpretation of EtR Domains \nWork Group Interpretation EtR Domain \nYes Public Health Problem Benefits and Harms \nLarge Benefits \nSmall Harms \nFavors intervention Benefit>Harm? \nValues \nProbably yes Desirable>Undesirable? \nPossibly important OR probably no important \nuncertainty or variability Uncertainty? \nProbably yes Acceptability \nProbably increased Equity \nProbably yes Feasibility \nProbably yes Resource Use \nBalance of consequences \nThere is \ninsufficient evidence to determine the balance of consequences Desirable consequences clearly \noutweigh \nundesirable consequences in most settings Desirable consequences \nprobably \noutweigh \nundesirable consequences in most settings The balance \nbetween the desirable and undesirable consequences is closely \nbalanced or \nuncertain Undesirable consequences \nprobably \noutweigh \ndesirable consequences in most settings Undesirable consequences clearly \noutweigh \ndesirable consequences in most settings \n•ACIP recommends the 2-dose* JYNNEOS vaccine series fo r persons 12 to 17 \nyears of age at risk of mpox during an mpox outbreak §.\n*Dose 2 administered one month after dose 1 §Public health authorities determine whether there i s an mpox outbreak; a \nsingle case may be considered an mpox outbreak at t he discretion of public \nhealth authorities. Other circumstances in which a public health response may \nbe indicated include ongoing risk of introduction o f mpox into a community \ndue to disease activity in another geographic area.Proposed Recommendation 1", "summary": "Agency for Toxic Substances and Disease Registry National Center for Environmental Health  Centers for Disease Control and Prevention  Evidence to Recommendations Framework: Vaccination with Jynneos for Adolescents at Risk of   Mpox During Outbreaks  Faisal Syed Minhaj, PharmD, MPH Poxvirus and Rabies Branch Centers for Disease Control and Prevention Advisory Committee on Immunization Practices April 15, 2025  •Structure to describe information considering in moving fr om evidence to  ACIP…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/03-minhaj-Mpox-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 56}
{"title": "04 minhaj Mpox 508", "content": "Agency for Toxic Substances and Disease Registry National Center for Environmental Health \nCenters for Disease Control and Prevention \nEvidence to Recommendations Framework: Routine Vaccination with Jynneos for Adolescents at  \nRisk of Mpox \nFaisal Syed Minhaj, PharmD, MPH Poxvirus and Rabies Branch Centers for Disease Control and Prevention Advisory Committee on Immunization Practices April 15, 2025 \nDoes ACIP recommend vaccination* with the 2-dose †JYNNEOS vaccine series \nfor persons aged 12–17 years at risk for mpox §?EtR Question \n*Interim recommendation to be revisited in 2-3 year s \n† Dose 2 administered 28 days after dose 1 \n§Persons at risk: \n1. Gay, bisexual, and other men who have sex with m en (MSM), or a person who has sex with \nMSM, who in the past 6 months have had one of the f ollowing: \n•A new diagnosis of ≥ 1 sexually transmitted disease  \n•More than one sex partner \n•Sex at a commercial sex venue \n•Sex in association with a large public event in a g eographic area where mpox \ntransmission is occurring \n2. Sexual partners of persons with the risks descri bed in above \n3. Persons who anticipate experiencing any of the a bove \nEvidence to Recommendation Domains \nQuestion(s) EtR Domain \n•Is the problem of public health importance? Public Health Problem \n•How substantial are the desirable anticipated effec ts? \n•How substantial are the undesirable anticipated eff ects? \n•Do the desirable effects outweigh the undesirable e ffects? Benefits and Harms \n•Does the target population feel the desirable effec ts are large relative to the \nundesirable effects? \n•Is there important uncertainty or variability in ho w much people value the \nmain outcome? Values \n•Is the intervention acceptable to key stakeholders? Acceptability \n•What would be the impact on health equity? Equity \n•Is the intervention feasible to implement? Feasibility \n•Is the intervention a reasonable and efficient allo cation of resources? Resource Use \nEtR Domain: Public Health Problem \nMpox current situation \nJynneos vaccine coverage in the United States among  people \nat risk for mpox – June 2022 through September 2024 \nOverall vaccine coverage \n1-dose: 42.2% and 2-dose: 26.2 % \nCumulative Monkeypox virus infections relative to \n2022, by immunity level — United States, 2023 \n>50% is needed \nto significantly \ndecrease the risk of \nlarge outbreaks Cumulative \nmonkeypox \nvirus \ninfections, \nrelative to \n2022 \n% Population at increased mpox risk with 1 or 2 dos es of Jynneos \nPollock ED. MMWR MorbMortal WklyRep 2023;72:568–573.\nhttps://www.cdc.gov/cfa-modeling-and-forecasting/mp ox-gbmsm-\ntechnical-brief/nov24-update/ \nU.S. mpox case trends in adolescents and children, \nMay 2022 through March 2025 \nCase Count Age \ngroup \n92 12-17 \n17 6-11 \n23 1-5\n15 <1 \n147 Total \n\nAre outbreaks of mpox of public health importance? \nNo Probably no Uncertain Yes \nVaries \nProbably Yes \nEtR Domain: Benefits and Harms \n•Adolescent arm met pre-specified criteria for non-inferior ity \n-GMT ratio of adolescents to adults was 1.60 (CI 1.3 2, 1.95) \n•Vaccine was safe and well tolerated in adolescents \n-Solicited systemic and local AEs were similar betwe en adolescents and adults \n•Systemic: 74% (CI 69, 79) vs 73% (CI 66, 79) \n•Local: 88% (CI 84, 91) vs 91% (CI 87,95) \n-Unsolicited related AEs: mainly injection site rela ted \n-Dizziness in adolescents is common with vaccine adm inistration in this age group \nand is not likely to represent a safety concern Adolescent safety and immunogenicity study summary \n•Vaccine adverse event reporting system (VAERS) 1\n-At least 1,245 vaccinees nationwide \n-One report of syncope \n-Three reports of unspecified mild local and systemi c reactions \n•VSD 2\n-88 vaccinees \n-No adverse events of special interest observed \n•V-safe 1\n-No participants were <18 years of age \n•EIND 3\n-57 vaccinees \n-21% reported local or systemic reactions. No seriou s adverse events were reported Adverse events among individuals <18 years of age \n1) https://pubmed.ncbi.nlm.nih.gov/38647241/ 2) htt ps://pubmed.ncbi.nlm.nih.gov/39565485/ 3) https://p ubmed.ncbi.nlm.nih.gov/36480476/ \nHow substantial are the desirable anticipated effects \nMinimal Small Moderate Large \nDon’t Know Varies \n\nHow substantial are the undesirable anticipated effects \nMinimal Small Moderate Large \nDon’t Know Varies \n\nDo the desirable effects outweigh the undesirable ef fects? \nFavors Intervention Favors Comparison Favors Both \nFavors Neither Unclear \n\nEtR Domain: Values \n•NIH rapidly completed trial recruitment \n•Participants were supportive in participating to help frien ds \n•Adolescent Medicine Trials Network for HIV/AIDS Intervent ions (ATN) \nyouth advisors were surveyed and 12/13 respondents we re supportive of \nvaccination \n•When an outbreak occurred (i.e., 2022 global outbreak) , pediatric close \ncontacts were vaccinated Values Considerations \nJYNNEOS first doses administered to children 17 yea rs \nand younger by sex May 2022 – September 2024 \nPersons with no age data available were removed fro m the analysis Total first doses Age group \n798 12-17 \n391 6-11 \n293 1-5\n150 <1 \n1,632 Total \nDoes the target population feel that the desirable effects are large relative to the undesirable effec ts? \nNo Probably no Uncertain Yes \nVaries \nProbably Yes \nIs there important uncertainty about or variability  in \nhow much people value the main outcomes? \nImportant uncertainty or variability Possibly important uncertainty or variability \nNo known undesirable outcomes \nProbably no important uncertainty or variability No important uncertainty or variability \nEtR Domain: Acceptability \n•Mothers from the survey do not view their children at r isk for mpox. \n-However, the intent to vaccinate is higher than exp ected. \n•Vaccines were primarily given to adolescents both through  public health \nand STI clinics. \n•Among 21 surveyed ATN providers who provide care for at-risk adolescents: \n-Over half already offer the mpox vaccine. \n-95% would recommend mpox vaccines for eligible pati ents and do not have \nconcerns about recommending the vaccine. \n-Majority expressed challenges associated with offer ing the vaccine; most \ncommon concern was financial cost to the clinic. Summary of Acceptability data \nIs the intervention acceptable to key stakeholders?\nNo Probably no Uncertain Yes \nVaries \nProbably Yes \nEtR Domain: Health Equity \nVaccine administrations* and cases in adolescents by  \nrace and ethnicity, May 2022 – March 2025 \nn=92 n=798 \n*Vaccine administration through September 2024, Case da ta \nthrough March 2025 +Includes 3 mpox cases indicating Multiple races. Mul tiple \nraces was not reported for vaccine administration da ta. \nIf Hispanic or Latino was indicated for ethnicity, Race/ethnicity is indicated as Hispanic or Latino; if Hispanic or \nLatino ethnicity was not indicated, Race/ethnicity is indicated \nas Race Vaccine Administrations Mpox Cases \n+\n•No groups or settings were disadvantaged by recommend ation for JYNNEOS \nuse during mpox outbreaks. \n•Immunogenicity is the same for immunocompetent persons 12-17 years. \n•Implementation of vaccine should assure equitable access.\n•Endorsement by ACIP could facilitate broad acceptance o f recommendation \n(e.g., insurance, health departments, pharmacies). Health Equity \nWhat would be the impact on health equity? \nReduced Probably Reduced Probably no impact Increased \nVaries \nProbably Increased \nDon’t know \n\nEtR Domain: Feasibility \n•Wide range of vaccinators can administer vaccine (pediatr icians, \npharmacists, public health nurses) \n•Wide range of potential facilities: public health, STI clinic, a dolescent health \nclinic, pediatrician offices \n•Same Immunization Information Systems (IIS) requirement s and reporting \ninfrastructure as other vaccines \n•Limitations to access \n-Poor access in rural communities \n-Cost of vaccine and 10 vial minimum ordering quanti ty could hinder practices \nstocking vaccine \n-Pediatricians may defer to STI/adolescent clinics Feasibility Considerations \n•Two doses, 28 days apart requires follow up and reminde rs \n•JYNNEOS, once thawed/refrigerated, is good for either 4 or 8 weeks, \nallowing time to schedule a second dose. \n•Frozen storage is ~18 months Feasibility Considerations \nIs the intervention feasible to implement? \nNo Probably no Uncertain Yes \nVaries \nProbably Yes \nEtR Domain: Resource Use \n•JYNNEOS is commercially available \n-Similar mechanisms for billing/reimbursement \n•Medicaid/Medicare/317 funding/VFC \n•Generally, vaccines are a good use of resources \n•Cost-effectiveness of vaccination in adolescents is uncer tain Resource Use \nIs the intervention a reasonable and efficient allocation of resources? \nNo Probably no Uncertain Yes \nVaries \nProbably Yes \nBalance of Consequences \nSummary of Work Group Interpretation of EtR Domains \nWork Group Interpretation EtR Domain \nYes Public Health Problem Benefits and Harms \nLarge Benefits \nSmall Harms \nFavors intervention Benefit>Harm? \nValues \nProbably yes Desirable>Undesirable? \nPossibly important OR probably no important \nuncertainty or variability Uncertainty? \nProbably yes Acceptability \nProbably increased Equity \nProbably yes Feasibility \nProbably yes Resource Use \nBalance of consequences \nThere is \ninsufficient evidence to determine the balance of consequences Desirable consequences clearly \noutweigh \nundesirable consequences in most settings Desirable consequences \nprobably \noutweigh \nundesirable consequences in most settings The balance \nbetween the desirable and undesirable consequences is closely \nbalanced or \nuncertain Undesirable consequences \nprobably \noutweigh \ndesirable consequences in most settings Undesirable consequences clearly \noutweigh \ndesirable consequences in most settings \nACIP recommends vaccination* with the 2-dose †JYNNEOS vaccine series for \npersons aged 12–17 years at risk for mpox §?Proposed Recommendation 2 \n*Interim recommendation to be revisited in 2-3 year s \n† Dose 2 administered 28 days after dose 1 \n§Persons at risk: \n1. Gay, bisexual, and other men who have sex with m en (MSM), or a person who has sex with \nMSM who in the past 6 months have had one of the fo llowing: \n•A new diagnosis of ≥ 1 sexually transmitted disease  \n•More than one sex partner \n•Sex at a commercial sex venue \n•Sex in association with a large public event in a g eographic area where mpox \ntransmission is occurring \n2. Sexual partners of persons with the risks descri bed in above \n3. Persons who anticipate experiencing any of the a bove \nTentative timeline for ACIP discussions and votes \nACIP Meeting: \nPresentation \nof two EtR \nApril 2025 ACIP Meeting: \nVoting on two \nEtR \nJune 2025 Continue monitoring \nmpox epidemiology \nand vaccine \nrecommendations \nOngoing \nThe findings and conclusions in this report are tho se of the authors and do not \nnecessarily represent the official position of the Centers for Disease Control and \nPrevention Thank you", "summary": "Agency for Toxic Substances and Disease Registry National Center for Environmental Health  Centers for Disease Control and Prevention  Evidence to Recommendations Framework: Routine Vaccination with Jynneos for Adolescents at   Risk of Mpox  Faisal Syed Minhaj, PharmD, MPH Poxvirus and Rabies Branch Centers for Disease Control and Prevention Advisory Committee on Immunization Practices April 15, 2025  Does ACIP recommend vaccination* with the 2-dose †JYNNEOS vaccine series  for persons aged…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/04-minhaj-Mpox-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 41}
{"title": "01 Marx Lyme 508", "content": "Introduction to the \nLyme Disease Vaccines Work Group\nGrace E. Marx, MD, MPH\nLead, Lyme Disease Vaccines Work Group\nApril 15, 2025\nAdvisory Committee on Immunization PracticesNational Center for Emerging and Zoonotic Infectious Diseases\n\n•Most common vector -borne disease in the U.S. \n•An estimated 476,000 people in the U.S. diagnosed and treated for Lyme \ndisease each year1\n•Estimated to cost $345– 968 million annually in health care costs2Public Health Problem –Lyme disease\n1. Kugeler K et al. Emerg  Infect Dis 2021: 27(2):616– 619. \n2. Hook S. et al. Emerg  Infect Dis 2022: 28(6):1170– 1179. \n•1990s \n-Several vaccines developed, each containing OspA  antigens from Borrelia burgdorferi\n-OspA  antibodies neutralize spirochete in the tick midgut, thus preventing \ntransmission\n-LYMErix ® licensed 1998; available  1998 – 2002 until discontinued by manufacturer \ndue to low demand\n•2010s – 2020’s \n-Steady increase in Lyme disease incidence, with expansion outward from high -\nincidence areas in the Northeast, mid -Atlantic, and Midwest\n-VLA15, a multivalent recombinant protein vaccine , currently in phase 3 clinical trials\n-mRNA vaccine candidates in early clinical trialsLyme Disease Vaccines Development\n•Review epidemiology and burden of Lyme disease\n•Review data about risk for Lyme disease\n•Review safety, immunogenicity, and efficacy data for Lyme disease vaccine \ncandidates\n•Review economic analyses related to Lyme disease vaccination\n•Develop Lyme disease vaccination policy options\n•Identify areas where additional data are neededACIP Lyme Disease Vaccines Work Group Objectives\n•Chair and work group members\n-TBD\n•Lead\n-Grace MarxACIP Lyme Disease Vaccines Work Group\n•May  2025 – first work group meeting\n•June 2025 – ACIP presentation\n-Epidemiology, burden, and clinical manifestations of Lyme diseaseACIP Lyme Disease Vaccines Work Group Initial Timeline\nFor more information, contact CDC\n1-800- CDC- INFO (232 -4636)\nTTY:  1 -888- 232- 6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.\nThank you.", "summary": "Introduction to the  Lyme Disease Vaccines Work Group Grace E. Marx, MD, MPH Lead, Lyme Disease Vaccines Work Group April 15, 2025 Advisory Committee on Immunization PracticesNational Center for Emerging and Zoonotic Infectious Diseases  •Most common vector -borne disease in the U.S.  •An estimated 476,000 people in the U.S. diagnosed and treated for Lyme  disease each year1 •Estimated to cost $345– 968 million annually in health care costs2Public Health Problem –Lyme disease 1. Kugeler K et…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/01-Marx-Lyme-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 7}
{"title": "03 influenza Shimabukuro 508", "content": "Highly Pathogenic \nAvian Influenza A \n(H5N1)\nTom Shimabukuro, MD, MPH, MBA\n \nInfluenza Division\nNational Center for Immunization and Respiratory \nDiseases (NCIRD)\nCenters for Disease Control and Prevention (CDC)\nOctober 23, 2024\nHPAI A(H5N1)/ HPAI A(H5)  Human Cases Since 1997\nPast Reported Global Human Cases with Highly Pathogenic Avian Influenza A(H5N1) (HPAI H5N1) by Country, 1997 -2024 | Bird Flu | C DC (Thru Aug 7, 2024; may include  A(H5)+, presumed H5N1 cases) 2\n\n•Historically, human infections have been \nthe result of:\n▪Poultry exposures \noDirect/close contact with sick or \ndead poultry\noVisiting a live poultry market\n▪Exposure to other infected animals\noDirect contact or close exposure \n(swans, dairy cows)\n▪Limited, non -sustained human -to-\nhuman transmission has occurred \nglobally in the past (not in the \nUnited States)Historical Human Exposures to HPAI A(H5N1) Viruses\n3\nCDC’s Priorities \n•Supporting and engaging  public \nhealth and agricultural partners\n•Protecting human health and \nsafety \n•Understanding risk to people \nfrom HPAI A(H5N1) viruses\n•Assessing HPAI A(H5N1) viruses \nfor genetic changes\nAvian Influenza Social Media Toolkit | Bird Flu | CDC\n4\n\nHPAI A(H5N1) Situation Update – Dairy Herds\n•As of October 18, 2024, USDA \nhas confirmed HPAI A(H5N1) \nin U.S. dairy herds in 324 \nfarms across 14 states\n▪Dairy cow illness was observed in \nearly 2024\n▪Significant decrease in milk \nproduction and quality\n▪March 25, 2024 : USDA reported \nHPAI A(H5N1) confirmed in cows \nfrom Texas and Kansas\nHighly Pathogenic Avian Influenza (HPAI) Detections in Livestock | Animal and Plant Health Inspection Service (usda.gov)  5\n\nHPAI A(H5) Human Cases, United States, During 2024 \n6\nH5 Bird Flu: Current Situation | Bird Flu | CDC  (all cases ≥18 years old, data through Oct 18, 2024)•Cases with dairy cattle and poultry exposures \nhave been clinically mild\n▪Mainly eye symptoms (conjunctivitis, eye \ndischarge)\n▪Some cases reported mild respiratory and \nsystemic symptoms (e.g., subjective fever)\n•The Missouri case had multiple underlying health \nconditions and was hospitalized with \ngastrointestinal symptoms, chest pain, and other \nsymptoms not typical of a respiratory illness and \ntested positive for influenza A\n▪Illness was not severe, patient treated with \noseltamivir and recovered\n▪Specimen was identified and confirmed as \nHPAI A(H5N1) through regular surveillance \n▪Serology results are pending on the case, a \nsymptomatic household contact of the case, \nand several exposed healthcare workers \nwho experienced mild respiratory illness\nInfluenza A(H5) Human Cases –Virus Sequences to Date\n•Sequences maintain primarily avian genetic characteristics and lack \nchanges that would make the virus better adapted to infect or spread \namong humans\n•Diagnostics :No impact to the current CDC influenza diagnostic \nassay's ability to detect A(H5N1) viruses\n•Treatments :No known markers of resistance to FDA approved antiviral \ndrugs for influenza \n•Candidate Vaccine Viruses (CVVs)\n▪Hemagglutinins of human influenza viruses remain antigenically related to two \navailable CVVs\nHow CDC is monitoring influenza data among people to better understand the current avian influenza A (H5N1) situation | Bird Flu | CDC7\n•All people with direct or close exposure to animals infected \nwith influenza A(H5N1) should be monitored for illness \nduring exposure and for 10 days after their last exposure\n•Signs/symptoms may include: \n▪feeling feverish, cough, sore throat, runny or stuffy nose, muscle or \nbody aches, headaches , fatigue , eye redness (or conjunctivitis) , \nshortness of breath or difficulty breathing\n▪less commonly, diarrhea, nausea, vomiting, or seizures\n•If signs/symptoms develop, seek medical evaluation for \npossible influenza testing and antiviral treatment\n•Symptomatic persons should isolate away from others during \nthis evaluation\n•State and local h ealth de partments are monitoring workers on \nimpacted farms and can facilitate testing and treatmentSymptom Monitoring Recommendations \nhttps://my.clevelandclinic.org/health/diseases/22401 -bird-flu\n8Highly Pathogenic Avian Influenza A(H5N1) Virus in Animals: Interim Recommendations for Prevention, Monitoring, and Public He alth \nInvestigations | Bird Flu | CDC ; Interim Guidance on Specimen Collection and Testing for Patients with Suspected Infection with Novel Influenza \nA Viruses Associated with Severe Disease or with the Potential to Cause Severe Disease in Humans | Bird Flu | CDC\n•CDC is continuing to \nsupport state and local \nhealth departments \nmonitoring exposed \npeople during and for 10 \ndays after last exposureOngoing Human Monitoring\nH5 Bird Flu: Current Situation | Bird Flu | CDC\nHow CDC is monitoring influenza data among people to better understand \nthe current avian influenza A (H5N1) situation | Bird Flu | CDC\n(Through Oct 18, 2024)\n9\n\nSince Feb 2024, public health laboratory monitoring includes testing of over 54,360 specimens using a protocol that \nwould have detected influenza A(H5) or other novel influenza viruses, 1 person has tested positive (the Missouri case)Surveillance, Human Monitoring, and Testing\nHow CDC is monitoring influenza data among people to better understand the current avian influenza A (H5N1) situation | Bird Flu | CDC , Weekly U.S. Influenza Surveillance Report | CDC10\nNo indicators of unusual influenza \nactivity in people, including avian \ninfluenza A(H5N1)\nFindings from a Michigan Seroprevalence Study\n•In June 2024, Michigan Department of Health collected blood \nsamples from 35 dairy workers\n▪had varying roles, but most worked with infected cows\n▪less than half reported using masks or goggles\n•Samples were tested for antibodies against influenza A(H5N1) \nvirus and a seasonal influenza virus\n•None of the participants showed neutralizing antibodies specific \nto avian influenza A(H5N1) virus, although many showed \nantibody responses to seasonal influenza virus\n•This suggests that these people were not previously infected \nwith influenza A (H5N1) despite high risk of exposure\n11\nFerret Studies\n•Ferret model permits study of influenza disease severity and transmissibility \nat the same time\n•Ferrets present with many clinical signs of infection shared by humans\n▪But not conjunctivitis\n•Limitations of ferret model\n▪Ferrets  in sustained contact 24/7\n▪Inoculation doses used in these studies may not be representative of natural exposure \nin humans\n▪Ferrets used in most studies have no preexisting antibodies to influenza, unlike most \nhumans who have had disease or vaccinations\n▪General limitations of animal models\n12\nPathogenesis and Transmission of Human Influenza \nA(H5N1) Viruses in Ferrets\n13*Pulit -Penaloza  et al, manuscript in press; †Brock et al, manuscript in preparationInfluenza A(H5N1) VirusMean  Max\nWeight Loss\n(inoculated ferrets)Lethality\n(inoculated ferrets)Direct Contact\nTransmission\n(ferrets co -housed)Resp Droplet\nTransmission\n(refer to image)\nA/Texas/37/2024(H5N1)\n(1st human case in 2024)* 13% 9/9 (100%) 3/3 (100%) 4/6 (66%)\nA/Michigan/90/2024 (H5N1)\n(2ndhuman case in 2024)†9.1% 0/6 (0%) 3/3 (100%) 2/3 (66%)\nRespiratory droplet (airborne) \ntransmission model\nInoculated ferretNaïve ferret\nDirect contact \ntransmission model\nFerret Studies Summary\n•Severity\n▪The Michigan human A(H5N1) virus caused less severe disease  in ferrets than the Texas \nhuman A(H5N1) virus\n▪Less mean maximum weight loss, 9.1% vs. 13%\n▪Lower lethality, 0/6 (0%) vs. 9/9 (100%)\n•Transmission\n▪The Michigan human A(H5N1) virus still transmits with some capacity by the respiratory \ndroplet route, similar to  what was observed with Texas human A(H5N1) virus\n•These findings are important because the Michigan human A(H5N1) virus \nbetter represents currently circulating viruses compared to the Texas human \nA(H5N1) virus\n14\nCDC Influenza Risk Assessment Tool (IRAT)\n•Evaluative tool for prioritizing \nresources for pandemic \npreparedness\n•Viruses scored using 10 risk \nelements by U.S. government \nsubject matter experts for \nemergence and public health \nimpact\n•Emergence  is the risk of a novel \ninfluenza virus acquiring the \nability to spread easily and \nefficiently in people\n•Public health impact is the \npotential severity of human \ndisease caused by the virus, the \nburden on society if a novel \ninfluenza virus were to begin \nspreading efficiently and \nsustainably among people1.Genomic variation \n2.Receptor binding\n3.Transmission in Laboratory animals\n4.Antivirals and Treatment Options\n5.Existing Population Immunity\n6.Disease Severity and Pathogenesis\n7.Antigenic Relationship to Vaccine Candidates\n8.Global Geographic Distribution\n9.Infection in Animals, Human Risk of Infection\n10.Human Infections and Transmission\nVirus\nPopulation\nEcology\nInfluenza Risk Assessment Tool (IRAT) | Pandemic Flu | CDC 15\n0.00.51.01.52.02.53.03.54.04.55.05.56.06.57.07.58.08.59.09.510.0\n0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5 5.5 6 6.5 7 7.5 8 8.5 9 9.5 10Impact\nEmergenceIRAT Virus Emergence and Impact – Comparison of Risk Scores\nInfluenza Risk Assessment Tool (IRAT) | Pandemic Influenza (Flu) | CDC• X: H5N1 clade 2.3.4.4b [A/Texas/37/2024ª] (X)\nEmergence = 5.8, Impact = 6.1\n• A: Highest emergence score Eurasian Avian/swine H1N1 in China\nEmergence = 7.5, Impact = 6.9\n• C: Highest Impact score avian H7N9 in China \n Emergence = 6.5, Impact = 7.5Data \nlabelInfluenza VirusEmergence \nScoreImpact \nScore\nA A(H1N1) [A/swine/Shandong/1207/2016] 7.5 6.9\nB A(H3N2) variant [A/Ohio/13/2017] 6.6 5.8\nC A(H7N9) [A/Hong Kong/125/2017] 6.5 7.5\nE A(H9N2) Y280 lineage [A/Anhui -Lujiang/13/2018] 6.2 5.9\nF A(H3N2) variant [A/Indiana/08/2011] 6.0 4.5\nX A(H5N1) clade 2.3.4.4b [A/Texas/37/2024A] 5.8 6.1\nG A(H1N2) variant [A/California/62/2018] 5.8 5.7\nI A(H5N6) clade 2.3.4.4b [A/Sichuan/06681/2021] 5.3 6.3\nJ A(H5N1) Clade 1 [A/Vietnam/1203/2004] 5.2 6.6\nKA(H5N1) Clade 2.3.4.4b [A/mink/Spain/3691 -\n8_22VIR10586 -10/2022]5.1 6.2\nL A(H5N6) [A/Yunnan/14564/2015] –like 5.0 6.6\nN A(H5N8) clade 2.3.4.4b [A/Astrakhan/3212/2020] 4.6 5.2\nOA(H5N1) clade 2.3.4.4b [A/American  \nwigeon/South Carolina/AH0195145/2021]4.4 5.1\nQ A(H5N8) [A/gyrfalcon/Washington/41088/2014] 4.2 4.6\nU A(H7N8) [A/turkey/Indiana/1573 -2/2016] 3.4 3.9\nVA(H7N9) [A/chicken/Tennessee/17 -007431 -\n3/2017]3.1 3.5X: Texas H5N1 2024\nK: mink/Spain H5N1 2022\nO: wigeon/SC H5N1 2021\n16\nIRAT Summary \n•The IRAT is an evaluative tool used by public health partners  for prioritizing \nresources for influenza pandemic preparedness\n•ItisNOT intended to predict a pandemic and is NOT to be used to assess the \noverall population risk nor individual risk\n•Using A(H5N1) clade 2.3.4.4b [A/Texas/37/2024(H5N1)] as the prototype virus, the \nscore remains in the \"moderate\" potential pandemic influenza risk category\n•The mean -high and mean -low acceptable score ranges for all the clade 2.3.4.4b \nviruses overlap, indicating that these viruses remain similar, and their overall risk \nscores remain \"moderate\"\n•Based on available data, CDC’s current assessment is that the risk to the general \npublic from avian influenza A(H5N1) virus remains low\n17\nPublic Health Risk\n•Overall risk to the public for HPAI A(H5N1) \nremains low\n•Greater risk for people with close, \nprolonged, or unprotected exposures to \ninfected animals, or to environments \ncontaminated by infected animals\n•Exposed individuals should monitor for \nsymptoms after first exposure and for 10 \ndays after last exposure\nHighly Pathogenic Avian Influenza A(H5N1) Virus in Animals: Interim \nRecommendations for Prevention, Monitoring, and Public Health \nInvestigations | Avian Influenza (Flu) (cdc.gov)\nAvian Influenza Social Media Toolkit | Bird Flu | CDC\n18\nAvian Influenza Social Media Toolkit | Bird Flu | CDC\nAvian Influenza Social Media Toolkit | Bird Flu | CDC\n19\nResources from CDC\nSituation Updates\nCDC A(H5N1) Bird Flu Response Update | Avian \nInfluenza (Flu)\nSurveillance Updates\nHow CDC is monitoring influenza data among people to \nbetter understand the current avian influenza A (H5N1) \nsituation | Avian Influenza (Flu)\nTechnical Report\nTechnical Report: Highly Pathogenic Avian Influenza \nA(H5N1) Viruses | Avian Influenza (Flu) (cdc.gov)\nUpdated Recommendations\nHighly Pathogenic Avian Influenza A(H5N1) Virus in \nAnimals: Interim Recommendations for Prevention, \nMonitoring, and Public Health Investigations \nRecommendations for Worker Protection and Use of \nPersonal Protective Equipment (PPE) to Reduce \nExposure to Novel Influenza A Viruses Associated with \nSevere Disease in Humans\n20\nAcknowledgments\nCDC Influenza Division\n•Virology, Surveillance, and Diagnosis Branch\n•Epidemiology and Prevention Branch\n•Immunology and Pathogenesis Branch\n•Global Influenza Branch\n•Office of the Director\nCDC 2024 Influenza A(H5N1) Response\n21\nThank you", "summary": "Highly Pathogenic  Avian Influenza A  (H5N1) Tom Shimabukuro, MD, MPH, MBA   Influenza Division National Center for Immunization and Respiratory  Diseases (NCIRD) Centers for Disease Control and Prevention (CDC) October 23, 2024 HPAI A(H5N1)/ HPAI A(H5)  Human Cases Since 1997 Past Reported Global Human Cases with Highly Pathogenic Avian Influenza A(H5N1) (HPAI H5N1) by Country, 1997 -2024 | Bird Flu | C DC (Thru Aug 7, 2024; may include  A(H5)+, presumed H5N1 cases) 2  •Historically, human…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-23-24-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/03-influenza-Shimabukuro-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 22}
{"title": "01 Chikungunya Asturias 508", "content": "CHIKUNGUNYA VACCINES\nACIP Meeting\nOctober 23, 2024\nEdwin Asturias, MD\nChair, ACIP Chikungunya Vaccines Work Group\n•Chikungunya Vaccines Work Group formed in May 2022 \n•Chikungunya vaccines \n-Live attenuated vaccine licensed in November 2023 (manufactured by Valneva)\n-Virus -like particle vaccine submitted to FDA for licensure (manufactured by \nBavarian Nordic) \n•Some recommendations developed, and others under development, for \nuse of chikungunya vaccines among U.S. persons at risk of chikungunya \nincluding travelers, laboratory workers, and residents of U.S. territories and \nstates with risk of transmissionBackground\n•October 2022– October 2023\n-Chikungunya virus disease and its sequelae\n-Chikungunya epidemiology globally and among U.S. travelers and laboratory \nworkers\n-Live attenuated chikungunya vaccine including immunogenicity, safety, and other topics\n•February 2024\n-ACIP approved recommendations for use of live attenuated chikungunya vaccine among U.S. travelers and laboratory workers\n•June 2024\n-Epidemiology of chikungunya in U.S. territories and states\n-Cost -effectiveness of use of live attenuated chikungunya vaccine among adults \nliving in U.S. territories Recap of previous Work Group ACIP presentations\n1. Update on chikungunya and chikungunya vaccines\n2. Virus -like particle chikungunya vaccine\n3. Work Group interpretation of chikungunya virus -like particle vaccine \ndataOverview of today’s session\nChikungunya Vaccines Work Group members\nACIP ACIP Liaisons Invited Consultants ( cont )\nEdwin Asturias, Univ Colorado Elizabeth Barnett, ISTM Margaret Ryan, DoD\nLin Chen, Mount Auburn Hosp James Campbell, AAP Steven Schofield, CATMAT\nMary Pat Friedlander, AAFP David Shlim, Jackson Hole Travel & Trop Med\nCDC Lead Saroj Rai, AIM Nestor Sosa, Uni New Mexico Hospital\nSusan Hills, DVBD Sanet Torres, San Jorge Children & Women's Hospital\nInvited Consultants Kirsten Vannice, Bill & Melinda Gates Foundation\nEx Officio Alan Barrett, Univ Texas Galveston Mary Wilson, Univ California San Francisco\nRobin Levis, FDA Beth Bell, Univ Washington\nSixun Yang, FDA Carina Blackmore, Florida Dept Health\nLesley Dupuy (NIH) Alan Lam, DoD\nChikungunya Vaccines Work Group CDC participants\nDVBD DGMH GRADE/ETR consultants\nSarah Guagliardo Kevin O’Laughlin Doug Campos -Outcalt\nAnn Powers Rebecca Morgan\nErin Staples DHQP\nParker Acevedo Michael McNeil ACIP Secretariat\nLaura Adams Jessica MacNeil, NCIRD\nJoshua Wong GID Leslie Lee, NCIRD\nPierre Muhoza\nNCEZID\nRita Helfand", "summary": "CHIKUNGUNYA VACCINES ACIP Meeting October 23, 2024 Edwin Asturias, MD Chair, ACIP Chikungunya Vaccines Work Group •Chikungunya Vaccines Work Group formed in May 2022  •Chikungunya vaccines  -Live attenuated vaccine licensed in November 2023 (manufactured by Valneva) -Virus -like particle vaccine submitted to FDA for licensure (manufactured by  Bavarian Nordic)  •Some recommendations developed, and others under development, for  use of chikungunya vaccines among U.S. persons at risk of…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-23-24-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/01-Chikungunya-Asturias-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 6}
{"title": "02 Chikungunya Hills 508", "content": "Update on chikungunya and chikungunya vaccinesNational Center for Emerging and Zoonotic Infectious Diseases\nSusan Hills MBBS MTH\nCDC Lead , Chikungunya Vaccines Work Group\nArboviral Diseases Branch\nDivision of Vector -Borne Diseases\nFort Collins, Colorado\nACIP Meeting, October 23, 2024\n•Mosquito -borne disease\n•Key vectors are Aedes aegypti \nand Aedes albopictus mosquitoesChikungunya \n2\nDistribution and virus transmission\nTypically tropical \nand subtropical \nregions\nPeriodically \ncauses large \noutbreaks, often \nwith high attack \nrates\nCountries and territories with current or past transmission of chikungunya \nvirus 3\nKey features of acute chikungunya virus disease\nFebrile illness with typically severe \narthralgia, can be debilitating\nOther symptoms include headache, rash, myalgia, anorexia\nNo anti -viral treatment available and \nmanagement is supportive\nImage above from : https://www.paho.org/en/topics/chikungunya\n4\n•Rare serious complications (e.g., \nmyocarditis, hepatitis, neurologic illness)\n•Deaths rare and reported mostly in\n-Older adults, particularly those with \ncomorbidities\n-Young infants infected perinatally or by mosquito bitesComplications of chikungunya\n5\nImage from : https://www.paho.org/en/topics/chikungunya\nBin S et al, Clin Case Rep 2023\n•Acute symptoms usually resolve in 7 –10 days\n•Some patients have continuation or relapse \nof symptoms\n•Ongoing arthralgia of variable severity might be present in up to ~50% at 3 months and \n~30% at 12 months\n1Chronic arthralgia following chikungunya\n1Based on recent meta -analysis (Lindsey N. Chronic arthralgia after chikungunya. US Advisory Committee on Immunization Practices meeting, June 2023)  6\n•Approximately 100 –200 reported cases \nannually\n•Infection most commonly acquired in \nlocations in Asia and Americas\n•Greatest risk factor for travelers is traveling to area with outbreakChikungunya among U.S. travelers\n7\nChikungunya vaccines\n•Manufactured by Valneva as IXCHIQ\n•Licensed November 9, 2023\n•Age group currently adults ≥18 years\n•Single dose schedule Live attenuated chikungunya vaccine \n9\n•ACIP recommends  the live attenuated chikungunya vaccine for persons \naged ≥18 years traveling to a country or territory where there is a \nchikungunya outbreak\n•In addition, the vaccine may be considered for the following persons \ntraveling to a country or territory without an outbreak but with evidence of chikungunya virus transmission among humans within the last 5 years\n-Persons aged >65 years, particularly those with underlying medical conditions, \nwho are likely to have at least moderate exposure* to mosquitoes, OR\n-Persons staying for a cumulative period of 6 months or moreRecommendations for travelers approved February 2024\n*Moderate exposure could include travelers who might have at least 2 weeks (cumulative) of exposure to mosquitoes in indoor o r \noutdoor settings10\n•ACIP recommends live attenuated chikungunya vaccine for \nlaboratory workers with potential for exposure to chikungunya \nvirusRecommendations for use among laboratory workers \napproved February 2024\n11\n•Adolescents aged 12 –17 years: expected submission to FDA in 2024\n•Children aged 1 –11 years: clinical trial began December 2023\n•Long term persistence trial ongoing\n-High seroresponse  rate (97%) at 2 years\n-Monitoring continuing through 10 years to determine if booster dose \nneeded in futureUpdates on live attenuated chikungunya vaccine\n12\n•Manufactured by Bavarian Nordic\n•Licensure possible February 2025\n•Intended age group is adolescents and adults aged ≥12 years\n•Single dose schedule Virus -like particle chikungunya vaccine\n13\nLicensure through accelerated approval pathway\nTraditional approval challenging and clinical development would likely \nhave been delayed\n–Efficacy trial with disease endpoint difficult as outbreaks unpredictable and \nduration can be relatively short\n–No established immunologic correlate of protection\nAccelerated approval pathway endorsed at FDA VRBAC* meeting, 2019\n–FDA can grant for products for serious conditions that fill unmet medical need\n–Effectiveness demonstrated by controlled trials showing vaccine has effect on surrogate endpoint reasonably likely to predict clinical benefit\n–Marker of protection for virus -like particle vaccine based on neutralizing \nantibody titer estimated from validated non -human primate model\n–Post -licensure requirement for controlled trials to confirm clinical benefit \n*Vaccines and Related Biological Products Advisory Committee 14\nACIP recommendations for use of chikungunya vaccines\nPopulation Live attenuated vaccine Virus -like particle vaccine\nTravelers Completed*Pending†\nLaboratory workers Completed Pending\nResidents of U.S. territories \nwith transmission risk Pending Pending\nResidents of U.S. states with transmission risk Pending Pending\n*Adults aged ≥18 years        †Adolescents and adults aged ≥12 years \nFor more information, contact CDC\n1-800- CDC- INFO (232 -4636)\nTTY:  1 -888- 232- 6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.", "summary": "Update on chikungunya and chikungunya vaccinesNational Center for Emerging and Zoonotic Infectious Diseases Susan Hills MBBS MTH CDC Lead , Chikungunya Vaccines Work Group Arboviral Diseases Branch Division of Vector -Borne Diseases Fort Collins, Colorado ACIP Meeting, October 23, 2024 •Mosquito -borne disease •Key vectors are Aedes aegypti  and Aedes albopictus mosquitoesChikungunya  2 Distribution and virus transmission Typically tropical  and subtropical  regions Periodically  causes…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-23-24-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/02-Chikungunya-Hills-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 16}
{"title": "03 Chikungunya Jenkins 508", "content": "CHIKV VLP vaccine\nBavarian Nordic’s chikungunya vaccine candidate\nOctober 2024\nVictoria Jenkins, PhD, MBA\nVP Regulatory Affairs & CHIKV Program LeadBavarian Nordic\nvije@bavarian -nordic.com\n2E protein\nMembrane\nCapsid shell\nRNA\nCHIKV VLP vaccine\nChikungunya virus3CHIKV virus -like particle vaccine (CHIKV VLP)1\nCHIKV, chikungunya virus; VLP, virus -like particle ; BLA, Biologics License Application; PDUFA, Prescription Drug User Free Act  \n1. Bennett SR, et al. Lancet Infect Dis. 2022;22(9):1343−1355. 2. Basore K et al. Cell. 2019 Jun 13;177(7):1725- 1737. 3. Sun S, et al. ELife. 2013;2:e00435\n•Comprised of 3 recombinant  chikungunya virus (CHIKV) \nstructural proteins that assemble into virus- like particles, which \nmimic  the CHIKV but cannot replicate\n•Adjuvanted with aluminum hydroxide; single 40 µg VLP dose (0.8 \nmL) in a pre -filled syringe; administered IM\n•Priority Review for the BLA granted by FDA (PDUFA target action date: 14th Feb 2025)\n•Proposed indication: prevention of disease caused by \nCHIKV infection in individuals 12 years of age and older\n•Proposed contraindications: hypersensitivity, including \nsevere allergic reaction (anaphylaxis), to any component\n•It was agreed with regulators to use a defined threshold of serum neutralizing antibodies as a surrogate endpoint of efficacy \nin phase 3 clinical trials\nCryo-electron microscopy reconstruction of CHIKV VLP2\n\nCHIKV- luciferase assay developed to evaluate v accine efficacy \nmeasures cross- neutralization\nVaccine strain\nAssay strainPhylogenetic analysis of CHIKV isolates based on a 1kb fragment in the E1 gene1\nAsian\nWest AfricanECSA\n3\n1. Parola P, de Lamballerie  X, Jourdan J, Rovery C, Vaillant V, Minodier  P, et al. Emerg  Infect Dis. 2006;12(10):1493- 1499. •CHIK181/25 live -attenuated virus (Asian \nlineage AF15561) engineered to express \nluciferase transgene (CHIKV -luc assay \nreporter)\n•Neutralization assay based on 80% (NT80) \nreduction of luciferase activity following Vero cell infection with CHIKV -luc\n•CHIKV -luc virus used in the assay is \nheterologous to the CHIKV VLP (Asian vs West African)\nECSA, East-Central -South -African    * CHIKV strain that was used as a challenge in nonhuman primate serum transfer study (next slide) *\nConservative serum neutralizing antibody (SNA) threshold chosen for phase 3 \nstudy immunogenicity endpoints based on NHP data & regulatory agency recommendations\nCHIKV, chikungunya virus; NHPs, nonhuman primate; SNA, serum neutralizing antibodies; CI, confidence interval\nData presented at ESCMID Global 2024 (not yet published in a peer- reviewed article)\n*FDA and EMASerum passive transfer and challenge \nstudy in NHP\n•NHPs received pooled sera from human \nparticipants vaccinated with CHIKV VLP at \nvarious dilutions i ntravenously and were \nchallenged  with CHIKV 24 hours later\n•Logistic regression model: \n•SNA titer of 50 results in 99.97% [81-100] \nprobability of protection against viremia\n•Regulatory agencies*  proposed and agreed a \nmore conservative SNA titer threshold of 100 \nto be an acceptable surrogate endpoint\nPredictedObserved\n95%-CI\nPre-challenge SNA Titer (Day 0)Probability of protection against viremia\n4\n\n1. Bennett et al. Safety and immunogenicity of PXVX0317, an aluminium  hydroxide -adjuvanted chikungunya virus -like particle vaccine: a randomized, double- blind, parallel -group, phase 2 trial. Lancet  Infect Dis. 2022;22(9):1343- 55. \n2. ClinicalTrials.gov ID: NCT05065983; 3. ClinicalTrials.gov ID: NCT03992872; 4. ClinicalTrials.gov ID: NCT05072080; 5. Clini calTrials.gov ID: NCT05349617. 6. Chang et al. Safety and tolerability of chikungunya virus- like particle vaccine in healthy adults: a phase 1 dose- escalation trial. Lancet,  vol. 384,9959 (2014):2046-\n52. 7. Goo et al. A virus -like particle vaccine elicits broad neutralizing antibody responses in humans to all chikungunya virus genotypes. J In fect Dis, vol. 214,10 (2016):1487- 1491. 8. Chen et al . Effect of a chikungunya virus -like particle vaccine on safety and tolerability outcomes: A randomized clinical trial. JAMA, vo l. \n323,14 (2020):1369- 1377. 9. McCarty et al . Chikungunya virus virus -like particle vaccine is well tolerated and immunogenic in chikungunya seropositive individuals. Vaccine, vol. 41,42 (2023):6146- 6149. 9\nBLA, Biologics license application 5CHIKV VLP vaccine clinical program\nStudy description Study designStudy phase \nand numberAge range \n(years)Number of participants\n(vaccine recipients)\n•Dose- and dose -schedule finding randomized, double -blind, \nparallel- groupPhase 21\nPXVX- CV-317-\n00118 - 45 445 (441)\n•Immunogenicity & Safety and tolerability of 40ug dose open labelPhase 22\nEBSI-CV-317-01018 - 45 25 (25)\n•Immunogenicity and safety in prior alphavirus vaccine \nrecipientsopen label, parallel -group Phase 23\nEBSI-CV-317-00218 - 65 60 (60)\n•Immunogenicity & Safety and tolerability\n•Lot-to-lot consistencyrandomized, double -blind, \nplacebo -controlledPhase  34 (pivotal)\nEBSI-CV-317-00412 - <65 3254 (2790)\n•Immunogenicity & Safety and tolerabilityrandomized, double -blind, \nplacebo -controlledPhase  35 (pivotal)\nEBSI-CV-317-005≥65 413 (206)\n\nImmune response according to dose and dosing schedule\nPXVX- CV-317-001\nPhase 2 \n6\n7•At year 1, Group 8 had significantly \nhigher GMTs vs Group 1 (491.7 vs \n243.4; p -value=0.0019); this was \nmaintained at year 2 (279.7 vs 169.8; \np-value=0.0369)\n•AEs mostly mild to moderate; no serious treatment -related unsolicited \nAEs\n•Local AEs more frequent in 40 ug adjuvanted CHIKV VLP group (40%) than in unadjuvanted group (23%)Single 40 µg CHIKV VLP adjuvanted dose had superior immunogenicity after \nfirst vaccination, showed a rapid and durable response, and was well -tolerated\nPrimary Endpoint: GMT of anti -CHIKV SNA level on Day 57 (28 days after last vaccination); adjuvant =  aluminum hydroxide\nVertical bars denote 95% confidence interval. GMT = geometric mean titer; NT80 = Neutralization Titer showing 80% neutralization\nBennett et al. Lancet Infect Dis. 2022;22(9):1343- 55.\n(n=42)(n=46)\n(n=42)(n=40)(n=38)(n=39)\n\nPivotal phase 3 studies\nEBSI-CV-317-004 in individuals 12 to <65 years\nEBSI-CV-317-005 in individuals ≥65 years\n8\nRichardson et al. Safety and Immunogenicity of an Adjuvanted Chikungunya Virus (CHIKV) Virus -like Particle (VLP) Based Vaccine in Two Pivotal Ph ase 3 Trials, ≥12 Years of Age. IDWeek oral presentation, 14 October 2023, Boston, MA.\nAE = adverse event; AESI = adverse event of special interest; MAAE = medically attended adverse event; SAE = serious adverse event9Design of the two pivotal phase 3 studies\nEnd of study\nPlacebo\n(n=464)Adolescents \nand Adults \n12 to <65 years CHIKV VLP \n(n=2790)\nCHIKV VLP\n(n=206)\nPlacebo\n(n=207)Adults ≥65 yearsEBSI-CV-317-004\nEBSI-CV-317-0051 15 22 29 phone 92 phone 183 Day:\nIP administrationScreening visit\n(within 30 days of Day 1)Treatment and observation Follow -up\nSolicited AEs\nUnsolicited AEs\nSAEs/AESI/MAAEs1 8 15 22 29 phone 92 phone 183 Day:Primary Immunogenicity Endpoint\n10Primary and key secondary objectives in phase 3 studies\nEBSI-CV-317-004\n12 to <65 years of age\nCoprimary :\n•SNA GMT at Day 22 versus placebo \n•Difference in seroresponse rate1 versus \nplacebo at Day 22\n•Safety\n•Lot consistency of anti- CHIKV SNA GMT at \nDay 22 (18 to 45 years)\nKey Secondary: \n•Seroresponse rates at Day 8, Day 15, Day \n183 versus placeboEBSI-CV-317-005\n≥65 years of age\nCoprimary :\n•SNA GMT at Day 22 versus placebo \n•Difference in seroresponse rate1 versus \nplacebo at Day 22\n•Safety\nKey Secondary: \n•Seroresponse rates at Day 15 and Day 183 \nversus placebo\n1 Seroresponse  rate (considered the presumptive seroprotection  rate) was defined as the percentage of participants who achieve a CHIKV -luc neutralization titer (NT80) ≥100\nGMT = geometric mean titer; SNA = serum neutralizing antibody\n\nBalanced demographic characteristics in study including adolescents \nand adults 12 to <65 years of age \n1 Demographic characteristics of the IEP are displayed. 2 Percentages are based on the number of participants in each study arm.\nBMI, body mass index; CHIKV, chikungunya virus; IEP, immunogenicity -evaluable population; LLOQ, lower limit of quantitation; SD, standard deviation; VLP, virus -like particle; B avarian Nordic data on file. Characteristic1 CHIKV VLP (n=2794) Placebo (n=464) Total (N=3258)\nAge (years)\nMean (SD) 39 (14.3) 39 (14.4) 39 (14.3)\nAge group, n (%)2\n12 to 17 years 217 (7.8) 37 (8.0) 254 (7.8)\n18 to 45 years 1636 (58.6) 270 (58.2) 1906 (58.5)\n46 to 64 years 941 (33.7) 157 (33.8) 1098 (33.7)\nSex, n (%)2\nMale 1358 (48.6) 233 (50.2) 1591 (48.8)\nFemale 1436 (51.4) 231 (49.8) 1667 (51.2)\nRace, n (%)2\nWhite 2043 (73.1) 341 (73.5) 2384 (73.2)\nAmerican Indian or Alaska Native 30 (1.1) 2 (0.4) 32 (1.0)\nAsian 79 (2.8) 16 (3.4) 95 (2.9)\nBlack or African American 534 (19.1) 89 (19.2) 623 (19.1)\nNative Hawaiian or Other Pacific Islander 6 (0.2) 4 (0.9) 10 (0.3)\nMultiracial 78 (2.8) 8 (1.7) 86 (2.6)\nNot reported 24 (0.9) 4 (0.9) 28 (0.9)\nEthnicity – n(%)2\nHispanic or Latino 506 (18.1) 71 (15.3) 577 (17.7)\nNot Hispanic or Latino 2226 (79.7) 379 (81.7) 2605 (80.0)\nNot reported 61 (2.2) 14 (3.0) 75 (2.3)\nUnknown 1 (<0.1) 0 1 (<0.1)\nBMI (kg/m2)\nMean (SD) 26.79 (4.53) 26.46 (4.61) 26.74 (4.54)\n\nBalanced demographic characteristics in study including adults ≥65 \nyears of age\n1 Demographic characteristics of the IEP are displayed. 2 Percentages are based on the number of participants in each study arm.\nBMI, body mass index; CHIKV, chikungunya virus; IEP, immunogenicity -evaluable population; LLOQ, lower limit of quantitation; SD, standard deviation; VLP, virus -like particle; B avarian Nordic data on file. Characteristic1CHIKV VLP (n=206) Placebo (n=207) Total (N=413)\nAge (years)\nMean (SD) 71 (5.3) 71 (4.5) 71 (4.9)\nAge group, n (%)2\n65 to 74 years 159 (77.2%) 159 (76.8%) 318 (77.0%)\n≥75 years 47 (22.8%) 48 (23.2%) 95 (23.0%)\nSex, n (%)2\nMale 81 (39.3%) 90 (43.5%) 171 (41.4%)\nFemale 125 (60.7%) 117 (56.5%) 242 (58.6%)\nRace, n (%)2\nWhite 176 (85.4%) 168 (81.2%) 344 (83.3%)\nAmerican Indian or Alaska Native 1 (0.5%) 1 (0.5%) 2 (0.5%)\nAsian 4 (1.9%) 1 (0.5%) 5 (1.2%)\nBlack or African American 20 (9.7%) 29 (14.0%) 49 (11.9%)\nMultiracial 4 (1.9%) 5 (2.4%) 9 (2.2%)\nNot reported 1 (0.5%) 3 (1.4%) 4 (1.0%)\nEthnicity – n(%)2\nHispanic or Latino 93 (45.1%) 90 (43.5%) 183 (44.3%)\nNot Hispanic or Latino 112 (54.4%) 116 (56.0%) 228 (55.2%)\nNot reported 1 (0.5%) 1 (0.5%) 2 (0.5%)\nBMI (kg/m2)\nMean (SD) 27.3 (3.98) 27.6 (3.90) 27.5 (3.94)\n\n13Rapid induction of robust anti -CHIKV seroresponse  rates and GMT in \nadolescents and adults 12 to <65 years of age \n(immunogenicity evaluable population) \n* Seroresponse  rate (considered the presumptive seroprotection  rate) was defined as the percentage of participants who achieved an anti -CHIK SNA NT80 titer ≥100 \n** Success criterion met: lower bound of the two -sided 95% CI on the difference in seroresponse  rates between CHIKV VLP vaccine and placebo groups ≥70%; \nVertical bars denote 95% confidence interval; CI = confidence interval; GMT = geometric mean titer; IEP  = immunogenicity evaluable population; SNA = serum neutralizing antibody; LLOQ = \nNote: 15 was the lower limit of quantitation (LLOQ) for the human SNA assay, so results <LLOQ were set to a titer of LLOQ/2 o r 7.5 for analysis\nData presented at IDWeek  2023, Data not yet published in a peer -reviewed article.Anti-CHIKV SNA GMT Anti-CHIKV SNA seroresponse rate \nP < 0.0001 for all time \npoints beyond Day 1P < 0.0001 for all time points beyond Day 1\n115 183 228931,0961,618\n338\n788 8\n1101001,00010,000\nCHIKV VLP (N=2,559)\nPlacebo (N=424)SNA GMT (NT80)\nStudy day115 183 228479798\n86\n020406080100\nCHIKV VLP (n=2,559)\nPlacebo (N=424)Seroresponse  rate* (%)\nStudy day\n•All co -primary endpoints were met:\n•At Day 22, the seroresponse rate difference between vaccine and placebo group was 96.6% (95% CI: 95.0%, 97.5%)**\n•At Day 22, the vaccine group GMT was significantly higher than that for placebo (1618 vs. 8; P<0.0001, ANOVA)\n•The pairwise lot comparison of SNA response to CHIKV VLP vaccine in adults aged 18 to 45 years demonstrated equivalence\n•All key secondary endpoints were metSeroresponse threshold\n14Rapid induction of robust anti -CHIKV seroresponse  rates and GMT \nin adults ≥65 years of age \n(immunogenicity evaluable population)  \nAnti-CHIKV SNA GMT\n378724\n233\n898 8\n1101001,00010,000\nCHIKV VLP (n=189)\nPlacebo (n=183)SNA GMT (NT80)Seroresponse  rate* (%)\nStudy day Study dayAnti-CHIKV SNA seroresponse rate\nP < 0.0001 for all time \npoints beyond Day 1\nP < 0.0001 for all time points beyond Day 1\n115 183 22 115 183 228287\n76\n020406080100\nCHIKV VLP (n=189)\nPlacebo (n=183)\n* Seroresponse  rate (considered the presumptive seroprotection  rate) was defined as the percentage of participants who achieved an anti -CHIK SNA NT80 titer ≥100 \nVertical bars denote 95% confidence interval; CI = confidence interval; GMT = geometric mean titer; IEP  = immunogenicity evaluable population; SNA = serum neutralizing antibody; LLOQ = lower limit of quantitation\nNote: 15 was the LLOQ for the human SNA assay, so results <LLOQ were set to a titer of LLOQ/2 or 7.5 for analysis\nData presented at IDWeek  2023, Data not yet published in a peer -reviewed article.Seroresponse  threshold\n•All co -primary endpoints were met\n•At Day 22, the seroresponse rate difference between vaccine and placebo group was 86.2% (95% CI: 72.3%, 84.6%) **\n•At Day 22, the vaccine group GMT was significantly higher than that for placebo (724 vs. 8; P<0.0001, ANOVA)\n•All key secondary endpoints were met\nCHIKV VLP vaccine was well -tolerated in individuals 12 to <65 years of age\nPlacebo CHIKV VLP Placebo CHIKV VLP Placebo CHIKV VLP21.9 10.0 0.3 0.0 0.3 0.01.7 0.7 0.1 0.10.1 0.0 0.04 0.0\n020406080100\nInjection site redness Injection site pain Injection site swellingIncidence (%)\n10.8 10.7 11.9 10.5 13.16.3 6.4 2.2 5.4 4.4 4.8 4.60.4 0.28.4 6.1 5.8 5.74.1 2.8 2.1 1.1 2.1 2.6 2.3 2.0 0.2 0.00.7 0.2 0.3 0.4 0.4 0.4 0.1 0.0 0.3 0.2 0.4 0.0 0.2 0.0\n020406080100\nFatigue Headache Myalgia Chills Arthralgia Nausea FeverLocal  solicited AEs Days 1 -8 (safety population)\nSystemic  solicited AEs Days 1 -8 (safety population)\n•Grade 3 (severe) local solicited AEs occurred in 5 (0.2%) CHIKV VLP vaccine recipients (4 injection site pain and 1 injection  site redness); \nno placebo recipients reported ≥Grade 3 events.   \n•Grade 3 (severe) systemic solicited AEs occurred in 41 (1.5%) CHIKV VLP vaccine recipients and in 2 (0.4%) placebo recipients.\n15\nIncidence (%)\nAEs = adverse events\nNote: One grade 4 (potentially life- threatening) systemic solicited AE of 105ºF fever was recorded in the electronic diary by a CHIKV VLP vaccine recipient, but the site deemed this entry an error.\n16Incidence of AESI and MAAE did not differ between the CHIKV VLP vaccine \ngroup and the placebo group  in individuals 12 to <65 years of age\nAE = adverse event; AESI = adverse event of special interest; MAAE = medically attended adverse event; SAE = serious adverse eve nt; SMC = safety monitoring committee; PT = preferred term. \nData presented at IDWeek  2023, Data not yet published in a peer -reviewed article.Unsolicited AEs Day 1 -29, and AESI, MAAEs and SAEs Day 1 -183 (safety population) \n15.8\n1.1 0.28.9\n0.813.4\n0.2 0.29.1\n0.2\n020406080100\nUnsolicited AE Unsolicited AE \n≥ Grade 3  AESI MAAE SAEIncidence (%)\n•AESI defined as defined as new onset or worsening arthralgia that was medically attended\n•One participant in the CHIKV VLP vaccine group had a severe (Grade 3) treatment-related unsolicited AE of dehydration, which \nresolved without medical intervention\n•There was one investigator assessed possibly related SAE (PT: retinal detachment) in the CHIKV VLP vaccine group that was assessed by the sponsor and independent SMC Chair as unrelated due to prior medical history of seeing ‘black spots’ in the right eye ( the \nsame eye with the retinal detachment) 1 month pre -study CHIKV VLP (n=2790)\nPlacebo (n=464)\n\n17CHIKV VLP vaccine was well -tolerated in individuals ≥65 years of age\nAEs = adverse events5.4 1.00.5 0.0 0.00.50.0\n020406080100\nPlacebo CHIKV VLP Placebo CHIKV VLP Placebo CHIKV VLP Injection site pain Injection site redness Injection site swellingIncidence  (%)\n3.9 5.0 2.4 5.0 2.9 7.0 1.5 2.0 2.4 3.0 2.0 1.5 0.0 0.52.4 1.5 3.4 1.0 1.0 0.5 1.5 2.0 0.5 1.0 0.50.5 0.5\n020406080100\nMyalgia Fatigue Headache Arthralgia Chills Nausea Fever\n•No participants experienced a grade 3 (severe) or higher local solicited AE\n•Solicited AEs occurred at similar rates between groups and were of grade 1 (mild) or 2 (moderate) intensity, except for one \nparticipant in the vaccine group who experienced two grade 3 (severe) systemic solicited AEs (headache and fatigue)Solicited  local AEs Days 1 -8 (safety population)\nSolicited  systemic  AEs Days 1 -8 (safety population)Incidence  (%)\n\n18Incidence of AESI and MAAE did not differ between the CHIKV VLP vaccine \ngroup and the placebo group  in individuals ≥65 years of age\nUnsolicited  AEs Days 1 -29, and AESI, MAAEs and SAEs Days 1 -183 (safety population) \n12.6\n1.9 0.09.2\n1.916.4\n1.4 0.511.1\n1.4\n020406080100\nUnsolicited AE Unsolicited AE \n≥ Grade 3 AESI MAAE SAEIncidence (%)\n•AESI defined as defined as new onset or worsening arthralgia that was medically attended\n•Fatigue and myalgia were the only treatment -related unsolicited AEs that each occurred in more than one participant \n•No SAE was considered treatment -related\nAE = adverse event; AESI = adverse event of special interest; MAAE = medically attended adverse event; SAE  = serious adverse event; SMC  = safety monitoring committee \nData presented at IDWeek  2023, Data not yet published in a peer -reviewed article.CHIKV VLP vaccine (n=206)\nPlacebo (n=207)\n\n19Analysis of serious adverse events, arthralgia, arthritis and osteoarthritis \nacross clinical trials1 reveals no safety signal\n1 Study PXVX- CV-317-001 Groups 8 and 10: 40 μg dose with 300 μg adjuvant single dose; studies EBSI -CV-317-002, EBSI -CV-317-010, EBSI -CV-317-004, and EBSI -CV-317-005. 2 There was 1 SAE (PT: retinal detachment) in the \nCHIKV VLP vaccine group that was considered possibly treatment -related by the study investigator but was assessed by the sponsor  and independent SMC Chair as unrelated due to prior medical historyEventCHIKV VLP vaccine \n40/300 µg  (N=3141)\nn (%)Placebo\n(N=675)\nn (%)\nAny Serious AEs 31/3141 (0.99) 4/675 (0.59)\nRelated Serious AEs2 0 0\nSolicited AE of arthralgia 230/3114 (7.39) 41/661 (6.20)\nArthralgia Grade 3 7/3114 (0.22) 1/661 (0.15)\nArthralgia duration >15 days 0 0\nUnsolicited Arthritis 1 (0.03) 0\nRelated arthritis 0 0\nUnsolicited osteoarthritis 1 (0.03) 0\nRelated osteoarthritis 0 0\n\nSummary: CHIKV VLP vaccine\n20\n•Single dose vaccine based on VLP technology, suitable for broad populations\n•PDUFA target action date: Feb 14th, 2025\n•Proposed indication: prevention of disease caused by CHIKV infection in individuals 12 years of age and older\nPDUFA, FDA Prescription Drug User Free Act •Well-tolerated\n•No treatment related SAEs as determined by sponsor\n•Most solicited and unsolicited adverse events mild or moderate in intensity•Phase 3 trials demonstrated rapid and robust immune response in individuals 12 years of age and older\n•Durable and boostable  immune response in a phase 2 trial", "summary": "CHIKV VLP vaccine Bavarian Nordic’s chikungunya vaccine candidate October 2024 Victoria Jenkins, PhD, MBA VP Regulatory Affairs & CHIKV Program LeadBavarian Nordic vije@bavarian -nordic.com 2E protein Membrane Capsid shell RNA CHIKV VLP vaccine Chikungunya virus3CHIKV virus -like particle vaccine (CHIKV VLP)1 CHIKV, chikungunya virus; VLP, virus -like particle ; BLA, Biologics License Application; PDUFA, Prescription Drug User Free Act   1. Bennett SR, et al. Lancet Infect Dis.…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-23-24-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/03-Chikungunya-Jenkins-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 20}
{"title": "04 Chikungunya Hills 508", "content": "Work Group interpretation of data for \nvirus -like particle chikungunya vaccineNational Center for Emerging and Zoonotic Infectious Diseases\nSusan Hills MBBS MTH\nCDC Lead , Chikungunya Vaccines Work Group\nArboviral Diseases Branch\nDivision of Vector -Borne Diseases\nFort Collins , Colorado\nACIP Meeting, October 23, 2024\n•No vaccine effectiveness data\n•Short -term* immunogenicity data available from ~2,750 \nvaccinated subjects in two Phase 3 studies\n-Majority adults aged 18 –64 years (~2350 subjects)\n-Smaller numbers of adolescents aged 12 –17 years and older adults \naged ≥65 years (~200 subjects in each group)Vaccine effectiveness (immunogenicity) data availability \n*Seroresponse  rates at 21 days after vaccination\n2\n•Robust response to vaccination with seroresponse  rates* at 21 days \nafter vaccination of 98% in adolescents/younger adults vs. 87% in \nolder adults\n•Relatively good seroresponse  rates maintained at 6 months after \nvaccination with rates in younger and older age groups of 86% vs. 76%\n•No longer -term (>6 months) data available from Phase 3 studies so \nneed for booster dose unknownKey immunogenicity results \n*Percent of subjects with anti -chikungunya virus 80% serum neutralizing antibody titer ≥100 3\n•Safety data available from ~3,000 vaccinated subjects in \ntwo Phase 3 studies\n-Majority adults aged 18 –64 years (~2,580 subjects)\n-Smaller numbers of adolescents aged 12 –17 years and older adults \naged ≥65 years (~210 subjects in each group)Safety data availability\n4\n•Solicited adverse events within 8 days of vaccination\n-Local: 24%; severe in 0.2%; m ostly injection site pain\n-Systemic: 32%; severe in 1.5%; fatigue, headache, and myalgia in 1 8%–20% \n•New onset or worsening arthralgia requiring medical attention in 0.2%\n•One serious adverse event (i.e., retinal detachment) assessed as related \nby investigator but unrelated by safety monitoring committee chair\n•All rates lower in older adults aged ≥65 yearsKey safety results in adolescents and adults aged 12 –64 years\n5\n•Will provide option, in addition to the licensed live attenuated vaccine, for \nvaccination of adults aged ≥18 years \n•Will provide option for adolescents aged 12 –17 years \n•Immunogenic vaccine but no vaccine effectiveness data which will be gathered post -licensure, and need for booster dose currently unknown\n•No apparent safety concerns but safety data only from ~3,000 people so \ninsufficient to detect rare events, and post -marketing surveillance important\n•Work Group to conduct comprehensive data review and present GRADE assessment as part of Evidence to Recommendations framework at future meetingWork Group summary for chikungunya virus- like \nparticle vaccine\n6\nChikungunya Vaccines Work Group plans\nAnticipated votes on vaccine recommendations, 2025\nPopulation Live attenuated vaccine Virus -like particle vaccine\nTravelers≥18 years completed\nYES† \nYES*\nLaboratory workers Completed YES\nResidents of U.S. territories \nwith transmission risk YES YES\nResidents of U.S. states with transmission risk YES YES\n*12– 17 years  †≥12 years\nFor more information, contact CDC\n1-800- CDC- INFO (232 -4636)\nTTY:  1 -888- 232- 6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.", "summary": "Work Group interpretation of data for  virus -like particle chikungunya vaccineNational Center for Emerging and Zoonotic Infectious Diseases Susan Hills MBBS MTH CDC Lead , Chikungunya Vaccines Work Group Arboviral Diseases Branch Division of Vector -Borne Diseases Fort Collins , Colorado ACIP Meeting, October 23, 2024 •No vaccine effectiveness data •Short -term* immunogenicity data available from ~2,750  vaccinated subjects in two Phase 3 studies -Majority adults aged 18 –64 years (~2350…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-23-24-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/04-Chikungunya-Hills-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 9}
{"title": "01 COVID Schechter 508", "content": "ACIP COVID -19 Vaccines Work Group\nRobert Schechter, MD\nCOVID -19 ACIP Work Group Chair\nAdvisory Committee on Immunization Practices Meeting\nOctober 23, 2024National Center for Immunization and Respiratory Diseases\n\n•To protect against COVID -19 disease, caused by SARS -CoV-2, ACIP recommended at its June 2024 \nmeeting the 2024 –2025 COVID -19 vaccines, as authorized or approved by FDA: ​\n-Moderna COVID -19 vaccine in persons ≥6 months ​\n-Pfizer -BioNTech COVID -19 vaccine in persons ≥6 months ​\n-Novavax COVID -19 vaccine in persons ≥ 12 years*​\n•Everyone aged 5 years and older should get 1 dose of a 2024 –2025 COVID -19 vaccine\n•Children aged 6 months– 4 years need multiple doses of COVID- 19 vaccines to be up to date, \nincluding at least 1 dose of 2024 –2025 COVID -19 vaccine\n•People who are moderately or severely immune compromised may receive additional doses of \n2024 –2025 COVID -19 vaccines under shared clinical decision making\n•No recommendation for additional doses of 2024 –2025 COVID -19 vaccine for older adultsCurrent 2024– 2025 COVID -19 vaccine recommendations \n*People who are previously unvaccinated for COVID -19 and are receiving Novavax should complete a 2 -dose initial series\n•To protect against COVID -19 disease, caused by SARS -CoV-2, ACIP recommended at its June 2024 \nmeeting the 2024 –2025 COVID -19 vaccines, as authorized or approved by FDA: ​\n-Moderna COVID -19 vaccine in persons ≥6 months ​\n-Pfizer -BioNTech COVID -19 vaccine in persons ≥6 months ​\n-Novavax COVID -19 vaccine in persons ≥ 12 years*​\n•Everyone aged 5 years and older should get 1 dose of a 2024 –2025 COVID -19 vaccine\n•Children aged 6 months– 4 years need multiple doses of COVID- 19 vaccines to be up to date, \nincluding at least 1 dose of 2024 –2025 COVID -19 vaccine\n•People who are moderately or severely immune compromised may receive additional doses of \n2024 –2025 COVID -19 vaccines under shared clinical decision making\n•No recommendation for additional doses of 2024 –2025 COVID -19 vaccine for older adultsCurrent 2024– 2025 COVID -19 vaccine recommendations \n*People who are previously unvaccinated for COVID -19 and are receiving Novavax should complete a 2 -dose initial series\nACIP COVID -19 Work Group Meeting Review\nJuly – October 2024\n•Seasonality of SARS- CoV-2\n•Epidemiology of COVID -19 \nin older adults and persons \nwith immunocompromise\n•SARS -CoV-2 variant updates\n•Vaccine safety updateRegarding additional doses of COVID -19 vaccine:\n•Vaccine effectiveness \n•Uptake and intent survey data\n•Economic analyses \n•Implementation\nAgenda: October 23, 2024\nIntroduction Dr. Robert Schechter (ACIP, WG Chair)\nCOVID -19 vaccine uptake and implementation Dr. Georgina Peacock (CDC/NCIRD)\nCOVID -19 epidemiology Dr. Christopher Taylor (CDC/NCIRD)\nCOVID -19 vaccine effectiveness Dr. Ruth Link -Gelles (CDC/NCIRD)\nEconomic analysis of an additional dose of the \n2024 -2025 COVID -19 vaccineDr. Lisa Prosser (University of Michigan)\nEvidence to Recommendations Ms. Lauren Roper (CDC/NCIRD)\nClinical considerations Dr. Lakshmi Panagiotakopoulos (CDC/NCIRD)\nVote Ms. Lauren Roper (CDC/NCIRD)\nIn addition to previously recommended 2024 –2025 vaccination: \n•ACIP recommends a second dose* of 2024– 2025 COVID -19 vaccine for adults ages \n≥65 years\n•ACIP recommends a second dose**  of 2024– 2025 COVID -19 vaccine for people \nages 6 months –64 years who are moderately or severely immunocompromised\n•ACIP recommends additional doses (i.e., 3 or more doses) of 2024– 2025 COVID -19 \nvaccine for people ages ≥6 months who are moderately or severely \nimmunocompromised under shared clinical decision makingVote language\n*If previously unvaccinated and receiving Novavax, 2 doses are recommended as initial vaccination series followed by a third dose of any age -\nappropriate 2024 -2025 COVID -19vaccine 6 months (minimum interval 2 months) after second dose​.\n**If previously unvaccinated or receiving initial vaccination series, at least 2 doses of 2024 –2025 vaccine are recommended, and  depending on \nvaccination history more may be needed. This additional 2024– 2025 vaccine dose is recommended 6 months (minimum interval 2 month s) after \ncompletion of initial vaccination series.​\n•During October 2023– April 2024, adults aged ≥65 years accounted for 70% \nof all COVID- 19–associated hospitalizations among adults. \n-Most hospitalized adults had multiple underlying medical conditions. \n-12% had received the recommended COVID -19 2023– 2024 formula vaccine.\n•During October 2022– April 2024, COVID- 19–associated hospitalization rates \nin infants aged <6 months were similar to those in adults aged 65 –74 years.\n-The percentage of hospitalized infants whose mothers had been vaccinated \nduring pregnancy was 18% during October 2022 –September 2023 and decreased \nto <5% during October 2023 –April 2024.Recent COVID -NET Reports Describe\nLow Immunization Rates in Hospitalized, High- Risk Populations \nwww.cdc.gov/mmwr/volumes/73/wr/mm7339a2.htm?s_cid=mm7339a2_w  \nwww.cdc.gov/mmwr/volumes/73/wr/mm7338a1.htm?s_cid=mm7338a1_w  \nWork Group members\nACIP members\n•Robert Schechter  (chair)\n•Noel Brewer\n•Oliver Brooks\n•George Kuchel\n•Keipp Talbot\nEx-officio/government members\n•BARDA: Christine Oshansky\n•CDC: Alan Lam\n•FDA: Adam Spanier, Rachel Zhang\n•IHS: Uzo Chukwuma\n•NIH: Chris Roberts\nCDC co -Leads\n•Lakshmi Panagiotakopoulos\n•Lauren RoperLiaisons\n•AAFP: Jonathan Temte\n•AAP: Sean O’Leary\n•ACOG: Naima Joseph (primary), \nLaura Riley (alternate)\n•ACP: Jason Goldman\n•AGS: Ken Schmader\n•AIM: Heather Roth\n•AMA: Sandra Fryhofer\n•ANA: Ruth Francis \n•APhA: Richard Dang\n•ASTHO: Marcus Plescia\n•CSTE: Paul Cieslak, Christine Hahn\n•IDSA: James McAuley Liaisons, cont’d\n•NACCHO: Matt Zahn\n•NACI: Eva Wong (primary), Matthew Tunis (alternate)  \n•NFID: Robert Hopkins (primary),   Bill Schaffner (alternate) \n•SHEA: Preeti Mehrotra (primary),                \nMarci Drees (alternate)\n   \nConsultants\n•Ed Belongia  \n•Hank Bernstein  \n•Matthew Daley\n•Kathy Edwards  \n•Lisa Jackson•Dayna Matthew\n•Jennifer Nelson\n•Stanley Perlman\n•Peter Szilagyi\nCDC participants \n•Amadea Britton\n•Mary Chamberland\n•Fatimah Dawood\n•Jonathan Duffy\n•Katherine Fleming -Dutra\n•Kristen Folsom\n•Julianne Gee\n•Monica Godfrey\n•Susan Goldstein\n•Lisa Grohskopf\n•Aron Hall \n•Elisha Hall\n•Demorah Hayes•Suzanne Heitfeld\n•Rita Helfand\n•Michele Hlavsa\n•Jefferson Jones\n•Ruth Link -Gelles\n•Jessica MacNeil\n•Josephine Mak\n•Seth Abram Meador\n•Michael Melgar\n•Sarah Meyer\n•Noelle -Angelique Molinari\n•Danielle Moulia\n•Ismael Ortega -Sanchez•Manisha Patel\n•Amanda Payne\n•Jamison Pike\n•Hannah Rosenblum\n•Sierra Scarbrough\n•John Su\n•Diya Surie\n•Natalie Thornburg\n•David Wentworth\n•Melinda Wharton\n•Trang Wisard\n•JoEllen Wolicki\nFor more information, contact CDC\n1-800- CDC -INFO (232- 4636)\nTTY:  1 -888- 232- 6348    cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the U.S. Centers for Disease Control and Prevention.", "summary": "ACIP COVID -19 Vaccines Work Group Robert Schechter, MD COVID -19 ACIP Work Group Chair Advisory Committee on Immunization Practices Meeting October 23, 2024National Center for Immunization and Respiratory Diseases  •To protect against COVID -19 disease, caused by SARS -CoV-2, ACIP recommended at its June 2024  meeting the 2024 –2025 COVID -19 vaccines, as authorized or approved by FDA: ​ -Moderna COVID -19 vaccine in persons ≥6 months ​ -Pfizer -BioNTech COVID -19 vaccine in persons ≥6 months…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-23-24-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/01-COVID-Schechter-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 10}
{"title": "02 COVID Peacock 508", "content": "Implementation Considerations for Additional \nCOVID -19 Vaccine Doses\nGeorgina Peacock, MD, MPH\nImmunization Services Division\nCenters for Disease Control and Prevention\nOctober 23, 2024National Center for Immunization and Respiratory Diseases\n\nCOVID -19 Vaccination Coverage and Intent for 2 Doses, \nNational Immunization Survey -Adult COVID Module\n2023 -2024 Data\n2-Dose Coverage and Intent Among Adults 65 Years \nand Older\nCOVID -19Vaccination Coverage (≥1 Dose and ≥2 Doses) A mong Adults 65Years \nand Older, 2023 -2024\nNational Immunization Survey -Adult COVID Module  (NIS- ACM)\n\nCOVID -19Vaccination Coverage A mong Adults 65Years and O lder, ≥2 Doses of \nthe 2023 -2024 Vaccine by End of June 2024\nNational Immunization Survey -Adult COVID Module  (NIS- ACM)\n21.813.516.29.011.18.112.76.78.311.17.49.09.210.69.18.78.9\n0.0 10.0 20.0 30.0 40.0 50.0 60.0AI/ANOther/multiple, non-…NH/OPIHispanicBlack, non-HispanicWhite, non-HispanicAsianRuralSuburbanUrban65-6970-7475-7980+MaleFemaleOverall 65+\nW eighted % (95% C I )9.48.48.510.510.78.818.011.17.87.76.88.97.39.38.08.4\n0.010.0 20.0 30.0 40.0 50.0 60.0Income unknownAbove poverty, >=$75KAbove poverty, <$75KBelow povertyUninsuredInsuredHHS Region 10HHS Region 9HHS Region 8HHS Region 7HHS Region 6HHS Region 5HHS Region 4HHS Region 3HHS Region 2HHS Region 1\nW eighted % (95% C I )*\n**\nAI/AN: American Indian or Alaska Native; NH/OPI: Native Hawaiian or Other Pacific Islander.\n*Statistically significant at p<0.05 (referent categories: Age 65 -69, Rural, White non- Hispanic, HHS Region 1).*\n\n7.213.68.79.713.97.710.38.69.38.7\n0.0 10.0 20.0 30.0 40.0 50.0 60.0No provider recommendationHealth care provider recommended…Does not have any disabilityHas a disabilityImmunocompromisedNo health conditionHas health conditionHigh SVIModerate SVILow SVI\nW eighted % (95% C I )COVID -19Vaccination Coverage A mong Adults 65Years and O lder, ≥2 Doses of \nthe 2023 -2024 Vaccine by End of June 2024\nNational Immunization Survey -Adult COVID Module  (NIS- ACM)\n*\n*\n*Statistically significant at p<0.05 (referent categories: No health condition, No provider \nrecommendation).\n36.8\n0.0 10.0 20.0 30.0 40.0 50.0 60.0Overall 65+\nWeighted % (95% CI)\n20.0 44.3 30.9 4.7\n0.0 50.0 100.0\nW eighted %COVID -19Vaccination Coverage and Intent for Second Dose A mong Adults 65\nYears and Older, April -June 2024\nNational Immunization Survey -Adult COVID Module  (NIS- ACM)\nPercent of adults 65+ who received \n≥1 dose of 2023 -24 Covid vaccine\nAmong adults 65+ who received \n≥1 dose of 2023- 24 Covid vaccine:\nReceipt /intent to receive 2nd dose\nProbably or definitely will not get another dose\nProbably will get another dose or unsureDefinitely will get another doseVaccinated with ≥2 doses of 2023- 24 Covid vaccine\n27.432.740.327.928.017.819.817.319.122.817.819.319.225.8\n41.034.627.235.238.046.638.545.444.743.245.843.745.441.2\n30.026.327.031.029.531.237.832.831.030.030.433.330.928.3\n1.56.45.55.94.44.53.94.55.24.16.03.74.64.7\n0.0 20.0 40.0 60.0 80.0 100.0AI/ANNH/OPIBlack, non-HispanicAsianRuralUrban65-6975-79\nW eighted %COVID -19Vaccination Coverage and Intent for Second Dose A mong Adults 65\nYears and Older, April -June 2024\nNational Immunization Survey -Adult COVID Module  (NIS- ACM)\nAmong adults 65+ who received ≥1 dose of 2023- 24 Covid vaccine:\nReceipt  and intent to receive 2nd dose\nAI/AN: American Indian or Alaska Native; NH/OPI: Native Hawaiian or Other Pacific \nIslander .\nProbably or definitely will not get another dose\nProbably will get another dose or unsureDefinitely will get another doseVaccinated with ≥2 doses of 2023- 24 Covid vaccine\nCOVID -19Vaccination Coverage and Intent for Second Dose A mong Adults 65\nYears and Older, April -June 2024\nNational Immunization Survey -Adult COVID Module  (NIS- ACM)\nAmong adults 65+ who received ≥1 dose of 2023- 24 Covid vaccine:\nReceipt  and intent to receive 2nd dose\n16.8 17.4 21.2 24.744.4 43.045.244.533.8 34.329.0 26.85.1 5.3 4.6 4.0\n0.020.040.060.080.0100.0\nApr-24 May-24 Jun-24 Jul-24W eighted %\nSurvey month\nProbably or definitely will not get another dose\nProbably will get another dose or unsureDefinitely will get another doseVaccinated with ≥2 doses of 2023- 24 Covid vaccine\n2-Dose Coverage Among Adults 18 Years and Older \nWho Are Immunocompromised\nCOVID -19Vaccination Coverage (≥2 Doses) A mong Adults 65Years and O lder \nand Adults 18 Years and Older Who Are Immunocompromised , 2024\nNational Immunization Survey -Adult COVID Module  (NIS- ACM)\n\nCOVID -19Vaccination Coverage A mong Adults 18 Years and Older Who Are Immunocompromised , ≥2 \nDoses of the 2023 -2024 Vaccine by End of June 2024\nNational Immunization Survey -Adult COVID Module  (NIS-ACM)\nNA: estimate not reported because denominator is <30; AI/AN: American Indian or Alaska Native; NH/OPI: Native \nHawaiian or Other Pacific Islander.\n*Statistically significant at p<0.05 (referent categories: Age 18 -49, Rural, White non- Hispanic, No Provider \nRecommendation, Insured).\n\nIntent to Receive 1, 2 or 3+ doses of 2024 -2025 COVID -\n19 vaccine if recommended\nOmnibus Surveys,  August 2024\n•Data are collected through the IPSOS KnowledgePanel  and NORC AmeriSpeak \nOmnibus Surveys, which use probability -based panels to survey a nationally \nrepresentative sample of U.S. adults ≥18 years of age on a set monthly \nschedule.\n•C DC  fields questions about vaccination status,  intent,  knowledge,  attitudes,  beliefs,  and behaviors on each survey for 2 waves each month,  for a combined \nsample size of ~4,000 per month.\n-These slides present combined results from August 2024 (N=4,224).\n•Data were weighted to represent the non -institutionalized U .S.  population and \nm itigate possible non -response bias.  All responses are self -reported.Omnibus Survey Methods\nhttps://www.ipsos.com/sites/default/files/ipsosknowledgepanelmethodology.pdf\nhttps://amerispeak.norc.org/content/dam/amerispeak/research/pdf/AmeriSpeak%20Technical%20Overview%202019%2002%2018.pdf  \n32.6 19.2 16.4 10.9 20.9\n25.0\n34.517.0\n19.819.0\n15.811.2\n10.827.8\n19.1\n36.7\n33.5\n23.920.3\n19.6\n16.814.7\n16.9\n18.211.3\n11.0\n10.217.0\n19.2\n30.9\n0 25 50 75 100Overall (N=1,263)\nAge 65+ (N=1,012)Age 18 -64 with health\nCondition (N=251)\nRural (N=265)Suburban (N=590)Urban (N=408)\nWeighted %47.5 28.0 20.6\n7.3 29.7 63.1\n30.9\n45.2\n35.8\n21.518.8\n23.3\n16.4\n23.915.4\n15.7\n18.5\n27.511.1\n10.9\n10.8\n8.823.8\n4.8\n18.6\n18.3\n34.1\n12.918.8\n25.716.6\n12.910.8\n8.919.8\n39.6\n0 25 50 75 100Definitely/probably would not\nget first dose (N=408)Definitely/probably would or unsure\nif would get first dose  (N=855)\nOther, non- Hispanic (N=56)Hispanic (N=121)Black, non- Hispanic (N=109)White, non- Hispanic (N=977)\nUninsured (N=42)Insured (N=1,160)\nWeighted %\n*Health condition includes cancer (excluding basal cell carcinoma and squamous cell carcinoma), solid organ or blood stem cell  transplant, HIV, and immunocompromised state. †NORC and Ipsos base urbanicity on different, but comparable \nmeasures. NORC uses Census tract -based RUCA (Rural -Urban- Commuting Area) codes, whereas Ipsos uses Office of Management and Budg et's CBSA (Core Based Statistical Area) classification. §Insured group includes plans purchased through \nemployer, insurance companies, marketplaces, military insurance, Medicare, Medicaid, VA, IHS, and \"other\". \n¶42 respondents excluded from analysis due to inconsistent answers.Intent to receive second 2024 -25 Covid -19 vaccination if recommended \namong adults ≥18 years of age with health conditions or ≥65 years of age, by \ndemographics ,*†§Omnibus Surveys, August 8 -26, 2024 (N=  1,263)¶\n•Based on data from the NIS -ACM, as of June 29, 2024, 8.9% of adults ≥65 \nyears reported receipt of ≥2 doses of the 2023 -24 COVID -19 vaccine\n-Among adults 65 years and older who received ≥1 dose of the 2023 -24 COVID -19 \nvaccine, 20.0% reported receiving a second dose\n•Based on Omnibus surveys fielded between August 8 -26, 2024, 34.5% of \nadults ≥65 years reported that they would definitely get two doses of the \n2024 -25 COVID -19 vaccine if recommendedTopline Summary \nImplementation considerations\n•Should an additional dose* of 2024 –2025 COVID -19 vaccine be \nrecommended for adults ages ≥65 years?\n•Should additional dose(s) of 2024 -2025 COVID -19 vaccine be \nrecommended for people ages ≥6 months who are moderately or severely \nimmunocompromised?Proposed policy questions\n*Recommended interval: 6 months since last 2024 -2025 dose, minimal interval: 2 months since last 2024- 2025 dose\n•Recommendations would not be \noverly burdensome to implement.\n-Additional dose recommendations \nwould be the same formula (2024 -\n2025) of COVID -19 vaccine currently \navailable.\n-Existing COVID -19 vaccine \nadministration infrastructure and product can be used.\n-The recommendation could be easily \nintegrated into existing systems and \nstructures (e.g., standing orders, \nCDSi ).Implementation considerations\n\n“Should” vs “may” recommendations\nBehavioral interventions for vaccination uptake: A systematic review and meta -analysis - PubM ed (nih.gov)“Should”\nE asier to communicate\nStrong call to action\nF ramed as normativeR emoves cognitive decision work“May”\nDifficult to communicate\nWeaker call to action\nFlexibility in decision makingAdds cognitive work\n•Minimum interval vs. Recommended interval\n•Recommended interval for vaccination\n-“Recommended” interval is consistent with language used for other vaccines, \nsowill be familiar to healthcare providers.\n-A recommended interval of 6 months is consistent with previous recommendations for additional doses for ages 65+.\n-Standardizing this interval across both 65+ and \nimmunocompromised populations will simplify schedule complexity.\n•Minimum interval for vaccination\n-A minimum interval of 2 months allows for flexibility of vaccine administration \nwhen accounting for individual risk and circumstances.Intervals for vaccination\n6.92.05.7\n0.2 0.481.9\n0.4 1.8 0.1 0.6\n0102030405060708090100 Percent (95% CI)Reported place of updated COVID -19 vaccination, adults aged ≥18 years, \nUnited States, National Immunization Survey -Adult COVID Module*\n*Among persons who reported receiving an updated 2024 -2025 COVID -19 vaccination since August 22, 2024 (n=2,943). Data collected September 1 -28, 2024.Place of 2024- 2025 COVID -19 Vaccination\n6.82.56.2\n0.1 0.382.8\n0.1 0.5 0.1 0.6\n0102030405060708090100 Percent (95% CI)Reported place of updated COVID -19 vaccination, adults aged ≥65 years, \nUnited States, National Immunization Survey -Adult COVID Module*\n*Among persons who reported receiving an updated 2024 -2025 COVID -19 vaccination since August 22, 2024 (n=1,715). Data collected September 1 -28, 2024.Place of 2024- 2025 COVID -19 Vaccination\n•“May” recommendations can be particularly challenging in these settings.\n-Current recommendation for further additional doses are “informed by the \nclinical judgment of a healthcare provider and personal preferences and \ncircumstances.”\n•Some challenges reported from pharmacy organizations or pharmacists:\n-Not all pharmacists feel this is within their scope of practice.\n-There is some discomfort with the patient conversations to make a vaccination \ndecision.\n•Some pharmacists feel they lack the time for these conversations.\n-Not all pharmacists have a clear understanding of moderate or severely immunocompromising conditions.\n-There are concerns about vaccinating the right patients for adequate \nreimbursement, which can lead to hesitation giving additional doses.Additional doses in pharmacy settings\n•Reports of people being denied vaccination tend to increase when there \nare changes to the guidance. More reports of denied vaccination occur \nwith additional doses.\n-For example, in February 2024 after recommendations for 65+ additional doses, \nreports of people who are immunocompromised being denied additional doses \nincreased.\n•CDC will work to assure recommendations are widely communicated to \nreduce confusion and avoid missed opportunities for vaccination.\n-Dedicated fall/winter workstream on healthcare provider engagement\n-Education and communications on recommendations and the importance of self -\nattestation to reduce barriers to vaccination\n-Wide array of partnershipsDenial of vaccination with frequent guidance changes\n•Social Determinants of Health drive differences in vaccine access creating \ndisparities in uptake. \n•Additional dose recommendations may further increase these disparities. \nFor e xample:\n-Insurance: decreased access with the end of the Bridge Access Program\n-Disability:  increased prevalence with age creating potential challenges getting to \nvaccination sites\n-Setting: decreased access in setting with existing challenges (e.g., long- term care)\n•In the absence of an ACIP recommendation, decreased access if required to \npay out -of-pocket.Vaccine equity considerations\nFor more information, contact CDC\n1-800- CDC -INFO (232- 4636)\nTTY:  1 -888- 232- 6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.", "summary": "Implementation Considerations for Additional  COVID -19 Vaccine Doses Georgina Peacock, MD, MPH Immunization Services Division Centers for Disease Control and Prevention October 23, 2024National Center for Immunization and Respiratory Diseases  COVID -19 Vaccination Coverage and Intent for 2 Doses,  National Immunization Survey -Adult COVID Module 2023 -2024 Data 2-Dose Coverage and Intent Among Adults 65 Years  and Older COVID -19Vaccination Coverage (≥1 Dose and ≥2 Doses) A mong Adults…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-23-24-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/02-COVID-Peacock-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 27}
{"title": "03 COVID Taylor 508", "content": "COVID -19–Associated Hospitalizations Update —  \nCOVID -NET, July 2023– September 2024\nAdults Ages ≥65 Years and Persons with Immunocompromising Conditions\nChristopher A. Taylor, PhD\nRESP -NET Hospitalization Surveillance Team\nCoronavirus and Other Respiratory Viruses Division\nMeeting of the Advisory Committee on Immunization Practices (ACIP)\nOctober 23, 2024National Center for Immunization and Respiratory Diseases\n1\nCOVID -NET is a population -based hospitalization \nsurveillance platform.\n•RESP -NET: COVID -NET, RSV -NET, FluSurv -NET\n•>300 acute -care hospitals\n•98 counties in 13 states\n-90 counties in 12 states for this analysis\ndue to incomplete data\n•Approx. 10% of the U.S. population\n•Positive SARS -CoV-2 test ≤14 days\nbefore admission or during\nhospitalization\n•Screening or clinician -driven testing\n•Clinical data: stratified random sample\n2\n\nCOVID -19–Associated Hospitalizations \nAmong Adults Ages ≥65 Years\n3\nAdults ages ≥65 years comprise 2/3 of all COVID- 19–\nassociated hospitalizations among adults.\nduring this same period of October 2023 through August 2024, children and adolescents ages 17 years and younger comprised 4% of all COVID -19-associated hospitalizations. 40%10%20%30%40%50%60%70%80%90%100%Percent of adults hospitalized with COVID -19\nSurveillance week end datePercent of weekly COVID -19–associated hospitalizations, by age group —\nCOVID -NET, March 2020 –September 2024\n18–49 years 50–64 years 65–74 years ≥75 years≥75 years=50%\n≥65 years=70%\nRates of COVID -19 hospitalizations are highest among \nadults ages ≥75 years.\n5020406080100120140160Rate per 100,000 population\nSurveillance week end dateWeekly rates of COVID -19–associated hospitalizations — COVID -NET, March 2020 –September 2024\n<6 months 6 months –4 years 5–11 years 12–17 years\n18–49 years 50–64 years 65–74 years ≥75 years\nAmong adults, rates of COVID- 19–associated \nhospitalizations increase with age.\n6581624191410\n02004006008001000120014001600\n10/7/2023\n10/21/2023\n11/4/2023\n11/18/2023\n12/2/2023\n12/16/2023\n12/30/2023\n1/13/2024\n1/27/2024\n2/10/20242/24/2024\n3/9/2024\n3/23/2024\n4/6/2024\n4/20/2024\n5/4/2024\n5/18/2024\n6/1/2024\n6/15/2024\n6/29/2024\n7/13/20247/27/2024\n8/10/2024\n8/24/2024\n9/7/2024\n9/21/2024R ate per 100,000 population\nSurveillance  week end dateCumulative rates of COVID -19–associated hospitalizations — COVID -NET, \nOctober 1, 2023 –September 28, 2024\n18–49 years 50–64 years 65–74 years ≥75 yearsAge groupRate ratio of \n≥75 years \nrelative to \nadult age \ngroups\n18–49 24.4\n50–64 8.7\n65–74 3.4\n≥75 1.0\nRates among adults ages \n≥75 years are many times \nhigher compared to \nyounger adults. \nRates of COVID -19–associated hospitalizations among \nadults ages ≥65 years have decreased over time.\n* The 2019– 2020 surveillance period includes March 2020 –September 2021.\n7050010001500200025003000\n*2019 –2020\n2020–2021\n2021–20222022–2023\n2023–2024\n*2019–2020\n2020–2021\n2021–20222022–20232023–2024\n*2019–2020\n2020–20212021–20222022–20232023–2024\n*2019–2020\n2020–20212021–2022\n2022–2023\n2023–2024\n*2019–2020\n2020–2021\n2021–2022\n2022–2023\n2023–202418–49 50–64 65–74 ≥75 ≥18R ate per 100,000 population\nA ge group and surveillance periodCumulative rates of COVID -19–associated hospitalizations — COVID -NET, March 2020 –September 2024\nMost adults ages ≥65 years hospitalized with COVID- 19 \nhave underlying medical conditions.\n•Among adults ages ≥65 years :\n-19% are residents of a long -term care facility (LTCF)\n-83% have ≥2 underlying medical conditions.\n•Among adults ages ≥75 years :\n-24% are residents of a LTCF\n-86% have ≥2 underlying conditions\nData are limited to hospitalizations where COVID -19 is a likely primary reason for admission during October 2023 –May 2024.8\nAdults ages ≥65 years remain at risk for severe \noutcomes during COVID- 19–associated hospitalization. \nData are limited to hospitalizations where COVID -19 is a likely primary reason for admission. 9Percent of outcomes and interventions among COVID -19–associated hospitalizations, by age group —\nCOVID -NET, October 2023 –May 2024\n18–49 50–64 ≥65\nL ength of stay ,  days (median) 2.9 3.4 3.5\nL ength of stay ,  days (I QR ) 1.4–5.5 1.9–7.9 1.9–7.1\nICU adm ission 17.9% 21.5% 17.7%\nInvasive m echanical ventilation 5.9% 12.8% 8.1%\nIn-hospital death 2.1% 11.3% 7.7%\nDuring this period, 80% of all adults hospitalized with COVID -19 who died in -hospital were ages ≥65 years. \nFewer than half of adults ages ≥65 years hospitalized with \nCOVID -19 received any COVID -19 vaccine since September 2022.\nData are limited to hospitalizations where COVID -19 is a likely primary reason for admission. 1075\n7067\n4753\n2124 243733\n4 6101715\n01020304050607080\n18–49 50–64 65–74 ≥75 ≥65Percent of adults hospitalized with C OV I D -19\nA ge groupVaccination status among adults with COVID -19–associated hospitalization, by age group —\nCOVID -NET, October 2023 –May 2024\nNo record of 2022–2023 (bivalent) or 2023–2024 formula\nR eceived 2022–2023 (bivalent), but not 2023–2024 formula\nR eceived 2023–2024 formula\nCOVID -19–Associated Hospitalizations \nAmong Persons with \nImmunocompromising Conditions\n11\nImmunocompromising conditions among patients \nhospitalized with COVID- 19 include:\n•AIDS or CD4 count <200\n•Complement deficiency\n•Graft vs. host disease\n•HIV infection\n•Immunoglobulin deficiency\n•Immunosuppressive therapy*\n•Leukemia**\n•Lymphoma**\n•Malignancy (solid organ)**•Bone marrow transplant\n•Metastatic cancer**\n•Multiple myeloma**\n•Steroid therapy***\n•Solid organ transplant\n•Other conditions typically associated \nwith immunocompromised status \nupon review\n* Within the 12 months before admission\n** Current/in treatment or diagnosed in the 12 months before admission\n*** Within 2 weeks before admission. Does not include inhaled, intranasal steroids or intramuscular or intra -articular injection  of steroids.12\nAbout 1 in 6 (15.6%) persons hospitalized with COVID- 19 \nhave an immunocompromising condition.\nData are limited to hospitalizations where COVID -19 is a likely primary reason for admission. 1316314 162215\n0%10%20%30%40%50%60%70%80%90%100%\nTotal 0–4 5–17 18–49 50–64 ≥65Percent of persons hospitalized with C OV I D -19\nA ge group (years)Immunocompromising condition among persons with COVID -19–associated hospitalization, by age group —\nCOVID -NET, July 2023 –May 2024\nImmunocompromising condition No immunocompromising condition\nThe most common immunocompromising conditions \namong persons hospitalized with COVID- 19 include:\n* Within the 12 months before admission\n** Current/in treatment or diagnosed in the 12 months before admission\n***  Within 2 weeks before admission. Does not include inhaled, intranasal steroids or intramuscular or intra -articular injectio n of steroids.\nData are limited to hospitalizations where COVID -19 is a likely primary reason for admission. 1446\n34\n26\n22\n9\n6\n5\n4\n3\n2\n1\n0.8\n0.1\n10 10 20 30 40 50\n* Immunosuppressive therapy\n** Solid organ malignancy\n*** Steroid therapy\n** Metastatic cancer\nSolid organ transplant\n** Lymphoma/Hodgkins/Non-Hodgkins\nHIV infection\n** Leukemia\nBone marrow transplant\nImmunoglobulin deficiency\n** Multiple myeloma\nAIDS or CD4 count <200\nGraft vs. host disease\nOther immunocompromising conditionsPercent of persons hospitalized with C OV I D -19Prevalence of immunocompromising conditions among persons hospitalized with COVID -19 with \nimmunocompromised status — COVID -NET, July 2023 –May 2024\nPrevalence  of conditions among \nthe 16% of hospitalized persons \nwith immunocompromising \nconditions\nFew persons with an immunocompromising condition hospitalized with \nCOVID -19 received any COVID -19 vaccine since September 2022.\n1567\n191470\n19\n11\n01020304050607080\nNo record of 2022–2023 (bivalent) or 2023–\n2024 formula doseR eceived 2022–2023 (bivalent) dose, but no \n2023–2024 formula doseR eceived 2023–2024 formula dosePercent of persons hospitalized with C OV I D -19\nV accination statusVaccination status among persons hospitalized with COVID -19, by immunocompromising status —\nCOVID -NET, October 2023 –May 2024\nImmunocompromising condition No immunocompromising condition\nTime since receipt of most recent COVID -19 vaccine \nvaries little by immunocompromising condition status.\nLimited to persons hospitalized with COVID -19 who received either a 2022– 2023 (bivalent) or 2023– 2024 formula COVID -19 vaccine s ince September 1, 2022. Data are limited to hospitalizations \nwhere COVID- 19 is a likely primary reason for admission. 1621322\n757\n5619\n961\n010203040506070\n≤30 days 31–60 days 61–120 days 121–180 days ≥180 daysPercent of persons hospitalized with C OV I D -19\nDays since vaccinationTime since receipt of most recent COVID -19 vaccine among persons hospitalized with COVID -19, by \nimmunocompromising status — COVID -NET, October 2023 –May 2024\nImmunocompromising condition No immunocompromising condition\nRisk for severe outcomes during COVID -19–associated \nhospitalization among children and adolescents varies little by \nimmunocompromising condition status. \nData are limited to hospitalizations where COVID -19 is a likely primary reason for admission. 1719\n6\n0.923\n5\n0.6\n0510152025\nICU admission Invasive mechanical ventilation In-hospital deathPercent of persons hospitalized with C OV I D -19Prevalence of outcomes and interventions among children and adolescents \naged ≤17 years hospitalized with COVID -19, by immunocompromising \ncondition status — COVID -NET, July 2023 –May 2024\nImmunocompromising condition No immunocompromising conditionSample size with I.C. condition = 103\nRisk for severe outcomes during COVID -19–associated \nhospitalization among adults varies by immunocompromising \ncondition status. \nData are limited to hospitalizations where COVID -19 is a likely primary reason for admission. 1827\n18\n15 15\n64\n051015202530\nICU admission Invasive mechanical ventilation In-hospital deathPercent of persons hospitalized with C OV I D -19Prevalence of outcomes and interventions among adults ages ≥18 years \nhospitalized with COVID -19, by immunocompromising condition status — \nCOVID -NET, July 2023 –May 2024\nImmunocompromising condition No immunocompromising conditionSample size with I.C. condition = 512\nQuestions\n19", "summary": "COVID -19–Associated Hospitalizations Update —   COVID -NET, July 2023– September 2024 Adults Ages ≥65 Years and Persons with Immunocompromising Conditions Christopher A. Taylor, PhD RESP -NET Hospitalization Surveillance Team Coronavirus and Other Respiratory Viruses Division Meeting of the Advisory Committee on Immunization Practices (ACIP) October 23, 2024National Center for Immunization and Respiratory Diseases 1 COVID -NET is a population -based hospitalization  surveillance platform.…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-23-24-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/03-COVID-Taylor-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 19}
{"title": "04 COVID Link Gelles 508", "content": "Effectiveness of COVID -19 vaccines \nRuth Link -Gelles, PhD, MPH\nCDR, US Public Health Service\nVaccine Effectiveness Program LeadCoronavirus and Other Respiratory Viruses DivisionCenters for Disease Control and Prevention October 23, 2024National Center for Immunization and Respiratory Diseases \n\n•VE data to inform need for:\n-Additional doses in immunocompromised\n•What’s known about VE in immunocompromised vs. non-\nimmunocompromised adults, including waning by time since dose\n-Additional dose for adults ≥65 years\n•What’s known about waning of a single dose in healthy adults ≥65 years, including against more severe outcomes\n•Benefits of an additional dose in past seasonsAgenda – COVID -19 vaccine effectiveness (VE)\n1. Time since dose impacts protection\n-How much and over what time period?\n2. SARS -CoV-2 variants change over time\n-Variant/vaccine match may impact effectiveness\n3. Surges in disease, seroprevalence, and time since last SARS -CoV-2 \ninfection impact measured VE\nDifficult to disentangle time since dose (true “waning”) vs. impact of \nchanges in variants vs. impact of time since prior infectionSome key issues in COVID- 19 vaccine effectiveness (VE)\n•High rates of SARS -CoV-2 infection -induced immunity by July – August 2023.*Context for interpreting COVID -19 VE across age groups: SARS -CoV-2 \nseroprevalence before 2023 -2024 respiratory virus season\n* Internal CDC data. Data on persons aged ≥16 years is from a longitudinal, national cohort of >35,000 blood donors.\nMethods and prior data available at: https://covid.cdc.gov/covid- data- tracker/#nationwide -blood -donor -seroprevalence- 202289%\n89%\n84%\n72%16-29 years\n30-49 years\n50-64 years\n≥65 years\n0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%\nPercent with infection- induced immunityPercent of persons with infection -induced immunity,\nbased on anti -nucleocapsid results from blood donors\nVE findings should be interpreted as the added benefit  provided by COVID -19 vaccination in a \npopulation with a high prevalence of vaccine - and infection -induced immunity.\nMeasuring COVID- 19 VE\nMeasure Definition Example \nvaccinated\ngroupExample comparison group\nAbsolute VE Compares frequency of health \noutcomes in vaccinated and unvaccinated people Received  \noriginal \nmonovalent \nCOVID -19 \nvaccineReceived no COVID -19 vaccines ever\nRelative VE Compares frequency of health outcomes in people who received one type of vaccine to people who received a different vaccineReceived  \nbivalent \nCOVID -19 \nvaccineEligible for, but did not receive, bivalent COVID -19 vaccine , but received \noriginal monovalent COVID -19 \nvaccine\nVE of 2023 -2024 COVID -\n19 vaccinesCompares people who received 2023 -2024  COVID -19 vaccine to \npeople who did not, regardless of past vaccinationReceived  \nupdated \n(2023 -24) \ndoseEligible for, but did not receive, an \nupdated (2023 -24) dose , regardless of \npast vaccination history \nMethods\nVISION Multi -Site Network of Electronic Health Records\n>300 emergency departments and urgent cares and >200 hospitals \nDesign: Test-negative design\nPopulation: Adults visiting a participating \nemergency department or urgent care (ED/UC) or \nhospitalized with COVID -19-like illness (CLI) with a \nSARS -CoV-2 NAAT test result within 10 days before \nor 72 hours after encounter\n−Cases: CLI with positive  NAAT for SARS -CoV-2 and no \npositive NAAT for RSV or influenza\n–Controls: CLI with negative  NAAT for SARS -CoV-2 and \nno positive NAAT for influenza\nVaccination data: Documented by electronic health records and state and \ncity registries\nIVY Network — 26 hospitals, 20 U.S. States\n•Design : Test-negative, case -control design\n•Population: Adults  aged  ≥18 years  hospitalized with COVID -\nlike illness (CLI)* and SARS -CoV-2 test results within 10 days of \nillness onset and 3 days of admission\n–Cases: CLI and test  positive  for SARS -CoV-2 by NAAT or antigen\n–Controls: CLI and test negative  for SARS -CoV-2 and influenza by \nRT-PCR\n•Vaccination data: Electronic medical records (EMR), state and \ncity registries, and plausible self -report\n•Specimens: Nasal swabs  obtained on all patients for central \nRT-PCR testing and whole genome sequencing\n*CLI is defined as presence of any one of the following: fever, cough, shortness of breath, chest imaging consistent with pneumoni a, or hypoxemia\n\n*Data sources included Medicare Enrollment Database (EDB) and Common Medicare Environment (CME), Common Working File (CWF) and S hared System Data (SSD) Medicare Parts A/B claims data, Minimum Data Set (MDS), and CDC/ATSDR \nSocial Vulnerability Index (SVI). Events identified from Medicare claims data using International Classification of Diseases,  Tenth Revision, Clinical Modification (ICD -10 CM) and common procedural terminology (CPT) codes. Medicare data\n• Design: Retrospective cohort\n• Data source:  Medicare fee- for-service claims data*\n• Population:  Persons aged ≥65 \n• Censoring events: ​\n– COVID -19-related thromboembolic event​\n– Death​\n– Disenrollment in Medicare Parts A/B​\n– Enrollment in Medicare Part C​\n– Nursing home stay lasting ≥100 days​\n– Admission to hospice facility​\n– Dialysis encounter\n– Receipt of multiple bivalent booster doses​\n– Bivalent booster dose < 60 days from the last COVID -19 vaccine \ndose\n– End of study period\n• VE = (1 - adjusted hazard ratio) x 100%\nwhere adjusted hazard ratio = 𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟  𝑜𝑜𝑜𝑜 𝑅𝑅𝑅𝑅𝑅𝑅  ℎ𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑟𝑟𝑟𝑟𝑜𝑜𝑜𝑜𝑜𝑜𝑟𝑟𝑟𝑟𝑜𝑜𝑜𝑜𝑜𝑜𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣\n𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟  𝑜𝑜𝑜𝑜 𝑅𝑅𝑅𝑅𝑅𝑅  ℎ𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑜𝑟𝑟𝑟𝑟𝑜𝑜𝑜𝑜𝑜𝑜𝑟𝑟𝑟𝑟𝑜𝑜𝑜𝑜𝑜𝑜𝑢𝑢𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣𝑣COVID -19 hospitalizationOther Censoring Event\nUnvaccinated person- time\nVaccinated person- time\nCOVID -19 VE data to inform need for \nadditional doses in persons with \nimmunocompromise\nAdjusted VE% (95% CI)\nVaccination \nstatus/days since doseImmunocompromised Not immunocompromised\n2 doses\n14-59 days 38 (-25-71) 81 (70- 88)\n60-119 days 27 (-7-51) 74 (66- 80)\n120-179 days 33 (6- 52) 64 (56- 71)\n180-239 days 35 (13- 51) 60 (53- 61)\n240-299 days 39 (27- 50) 57 (53- 61)\n300+ days 42 (29- 52) 66 (62- 69)\n3 doses\n14-59 days 81 (75- 85) 93 (91- 94)\n60-119 days 74 (68- 78) 91 (90- 92)\n120-179 days 49 (37- 58) 84 (81- 87)VISION: Original monovalent vs. unvaccinated  mRNA VE for COVID -19-associated hospitalization  by \nnumber of doses and time since last dose receipt for adults ≥50 years, Dec 2021– Mar 2022, by \nimmunocompromised status\nAdapted from Britton et al. MMWR: https://www.cdc.gov/mmwr/volumes/71/wr/mm7142a4.htm . Individuals with prior infections excluded. Logistic regression conditioned on calendar \nweek and geographic area, and adjusted for age, sex, race, ethnicity, local virus circulation, respiratory or nonrespiratory  underlying medical conditions, and propensity to be vaccinated 11-40 -20 0 20 40 60 80 100\nVaccine  E ff ectiveness (%)   Immunocompromised     Not immunocompromised\nVE of original mRNA doses vs. unvaccinated persons during Delta and early Omicron was higher among non -immunocompromised adults.  An \nadditional dose restored/increased protection in immunocompromise and non -immunocompromised, with some waning apparent. \nAdjusted VE% (95% CI)\nVaccination \nstatus/days since doseImmunocompromised Not immunocompromised\n2 doses\n14-59 days 38 (-25-71) 81 (70- 88)\n60-119 days 27 (-7-51) 74 (66- 80)\n120-179 days 33 (6- 52) 64 (56- 71)\n180-239 days 35 (13- 51) 60 (53- 61)\n240-299 days 39 (27- 50) 57 (53- 61)\n300+ days 42 (29- 52) 66 (62- 69)\n3 doses\n14-59 days 81 (75- 85) 93 (91- 94)\n60-119 days 74 (68- 78) 91 (90- 92)\n120-179 days 49 (37- 58) 84 (81- 87)VISION: Original monovalent vs. unvaccinated  mRNA VE for COVID -19-associated hospitalization  by \nnumber of doses and time since last dose receipt for adults ≥50 years, Dec 2021– Mar 2022, by \nimmunocompromised status\nAdapted from Britton et al. MMWR: https://www.cdc.gov/mmwr/volumes/71/wr/mm7142a4.htm . Individuals with prior infections excluded. Logistic regression conditioned on calendar \nweek and geographic area, and adjusted for age, sex, race, ethnicity, local virus circulation, respiratory or nonrespiratory  underlying medical conditions, and propensity to be vaccinated 12-40 -20 0 20 40 60 80 100\nVaccine  E ff ectiveness (%)   Immunocompromised     Not immunocompromised\nVE of original mRNA doses vs. unvaccinated persons during Delta and early Omicron was higher among non -immunocompromised adults.  An \nadditional dose restored/increased protection in immunocompromise and non -immunocompromised, with some waning apparent. \nIVY: Original monovalent and bivalent vs. unvaccinated mRNA VE against COVID -19-associated \nhospitalization by time since last dose receipt for adults ≥18 years, September 2022 –August \n2023, by immunocompromised status\nDeCuir J. medRxiv 2024.01.07.24300910; doi:https://doi.org/10.1101/2024.01.07.24300910\nA dose of bivalent vaccine added protection among those >1 year from their last original monovalent dose during Omicron predo minance. \nIVY: Original monovalent and bivalent vs. unvaccinated mRNA VE against COVID -19-associated \nhospitalization by time since last dose receipt for adults ≥18 years, September 2022 –August \n2023, by immunocompromised status\nDeCuir J. medRxiv 2024.01.07.24300910; doi:https://doi.org/10.1101/2024.01.07.24300910\nA dose of bivalent vaccine added protection among those >1 year from their last original monovalent dose during Omicron predo minance. \nIVY: Original monovalent and bivalent vs. unvaccinated mRNA VE against COVID -19-associated \nhospitalization by time since last dose receipt for adults ≥18 years, September 2022 –August \n2023, by immunocompromised status\nDeCuir J. medRxiv 2024.01.07.24300910; doi:https://doi.org/10.1101/2024.01.07.24300910\nA dose of bivalent vaccine added protection among those >1 year from their last original monovalent dose during Omicron predo minance. \nVISION: VE of 2023 -2024 vs. no 2023 -2024  COVID -19 vaccine against COVID -19-associated \nhospitalization among adults aged ≥18 years, by immunocompromise status\nSeptember 2023 – August 2024\n16Adjusted VE% (95% CI)\nDays since \nvaccinationImmunocompromised Not immunocompromised\n7-59 days 36 (22- 48) 51 (45- 56)\n60-119 days 23 (6- 36) 42 (35- 48)\n120-179 days 1 (-28-23)* 15 (3- 26)\n-40 -20 0 20 40 60 80 100\nVaccine  E ff ectiveness (%)   Immunocompromised     Not immunocompromised\nDuring the 2023- 2024 season, VE appeared somewhat lower in immunocompromised individuals, though waning \npatterns were similar to those in non- immunocompromised individuals.\nCDC, preliminary unpublished data. Individuals with prior infections excluded. Logistic regression conditioned on calendar we ek and geographic area, and adjusted for age, \nsex, race, ethnicity, local virus circulation, respiratory or nonrespiratory underlying medical conditions, and propensity to  be vaccinated\nConclusions: VE among those with \nimmunocompromising conditions\n•COVID -19 vaccines provided protection for both persons with and without \nimmunocompromise.\n•Patterns of COVID -19 VE in immunocompromised were different season- to-season, with \ngenerally lower VE compared to non- immunocompromised, but inconsistent waning \npatterns.\n-During 2023- 2024, VE against hospitalization in immunocompromised waned to 0 by ~4 -6 \nmonths.\n•This inconsistency is likely multifactorial, including:\n-Heterogeneity among those classified as immunocompromised\n-Variation in underlying immunity and response to prior  infection\n-Differing health behav iors (e.g., masking, social distancing) over time and by immunocompromise status\n17\nCOVID -19 VE data to inform need for an \nadditional COVID -19 vaccine dose for \nadults aged ≥65 years\nCOVID -19 VE against COVID- 19-associated hospitalization  wanes over time, but is more \nsustained against COVID -19-associated critical illness , though some waning is evident\nData from VISION and IVY showing VE by vaccine formulation of most recent dose.\n-20020406080100\n7-59 or 14-59 60-119 120-179 180-239* 240-299* 300-364* 365+Vaccine effectiveness (%)\nDays since last dose\nRecipients of bivalent and 2023 -2024 doses included in this analysis received a single dose of the most recent formulation.\nSources: DeCuir, et al., MMWR 2023/  Lin k-Gelles, ACIP Slides, April 20, 2022 ; CDC unpublished data updated from Link -Gelles, ACIP Slides, June 23, 2023 ; CDC unpublished data updated from: Link -Gelles, ACIP Slides, June 27, 2024\n* For original monovalent doses, VE for hospitalization was for 180 -364 days from last dose combined. For 2023- 2024 doses, VE fo r hospitalization was for ≥180 days combined, with a median of 228 days (IQR: 202 -259).Hosp italization Critical illness\nOriginal monovalent (adults aged 50+; ref: unvaccinated)\nBivalent (adults aged 18+; ref: unvaccinated)  \n2023- 2024 (adults aged 18+; ref: no 2023- 2024 dose)  \nSARS -CoV-2 variant period/\nmRNA dosage pattern/\ndays since doseMedian (IQR) days\nfrom last doseVaccinated\ncase-patients\n no./total no. (%)Vaccinated\ncontrol -patients,\nno./total no. (%)Adjusted VE (95% CI)   s\nBA.1/BA.2 period\n2 original monovalent doses\n14-150 days 111 (87 –130) 62/771 (8) 79/514 (15) 63 (46 –75)\n>150 days 290 (241 –351) 471/1,180 (40) 404/839 (48) 34 (20 –46)\n3 original monovalent doses\n7-120 days 80 (55 –100) 167/876 (19) 393/828 (47) 79 (74 –84)\n>120 days 180 (154 –208) 265/974 (27) 301/736 (41) 41 (23 –55)\nBA.4/BA.5 period\n2 original monovalent doses\n14-150 days 102 (77 –123) 3/189 (2) 13/168 (8) 83 (35 –96)\n>150 days 430 (329 –471) 128/314 (41) 168/323 (52) 37 (12 –55)\n3 original monovalent doses\n7-120 days 74 (33 –110) 13/199 (7) 24/179 (13) 60 (12 –81)\n>120 days 237 (204 –269) 219/405 (54) 208/363 (57) 29 (3 –48)IVY: Original monovalent vs. unvaccinated VE against COVID -19-associated hospitalization  \namong immunocompetent adults ≥18 years, by Omicron sublineage period\nDecember 2021- August 2022  \nSurie and Bonnell, et al. MMWR, https://www.cdc.gov/mmwr/volumes/71/wr/mm7142a3.htm  200 20 40 60 80 100\nVE of an additional original monovalent dose provided increased protection during Omicron with similar waning patterns for 2 and 3 doses.\nSARS -CoV-2 variant period/\nmRNA dosage pattern/\ndays since doseTotalSARS -CoV-2-\ntest-positive,\nN (%)Median interval\nsince last dose,\ndays (IQR)Adjusted VE (95% CI)\nBA.4/BA.5 period\nUnvaccinated (ref) 2,971 743 (25) --\n2 original monovalent doses\n14-149 days 77 14 (18) 80 (57- 105) --\n≥150 days 2828 556 (20) 473 (422- 503) 31 (21- 39)\n3 original monovalent doses\n7-119 days 289 26 (9) 72 (42- 98) 73 (55 -84)\n≥120 days 4838 913 (19) 240 (211- 266) 38 (30- 46)\n4 original monovalent doses\n7-59 days 765 89 (12) 38 (23- 50) 66 (53 -75)\n≥60 days 1549 210 (14) 88 (75- 105) 57 (44 -66)VISION: Original monovalent vs. unvaccinated VE against COVID- 19-\nassociated hospitalization  among immunocompetent adults ≥65 years\nJune -August 2022  \nLink-Gelles, et al. JAMA Network Open, https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2802473 , 2023 210 20 40 60 80 100\nVE of an additional original monovalent dose provided increased protection during Omicron with similar waning patterns for 2 and 3 doses.\nIVY: Original monovalent and bivalent vs. unvaccinated  VE against COVID -19-\nassociated severe in -hospital outcomes among adults aged ≥18 years without \nimmunocompromising conditions\nDeCuir et al., 2024, under reviewVE of COVID -19 vaccines was most durable against the most severe outcomes.\nmRNA Dosage Pattern/time since doseNo. of\nbeneficiariesNo. of\nCOVID -19\nrelated TETotal no. of\nperson -daysMedian follow-\nup days\ncontributed to\ncategoryAdjusted VE (95% CI)\nOriginal monovalent vaccine dose (ref) 7,022,968 17,746 1,505,533,898 181 Ref\nBivalent dose 5,683,208 4,255 694,184,995 130 47 (45– 49)\nBivalent dose 7 -59 days earlier 350,021 1,492 294,516,234 53 54 (51– 56)\nBivalent dose ≥60 days earlier 5,333,187 2,763 399,668,761 77 42 (39– 45)\n0 20 40 60 80 100\nVaccine  Effectiveness (%)Medicare: VE of bivalent  vs. original monovalent COVID -19 vaccine \nagainst COVID- 19-related thromboembolic events  among \nimmuno competent  Medicare beneficiaries aged ≥65 years\nSeptember 2022 – March 2023\nVE estimates adjusted for age, sex, race and ethnicity, geographic region, and calendar time. Updated from: Link -Gelles et al., MMWR, \nhttps://www.cdc.gov/mmwr/volumes/72/wr/mm7221a3.htm  \nTE = thromboembolic event*A COVID -19–related thromboembolic event was defined as presence of an International Classification of Disease, 10th \nEdition  (ICD -10) or common procedural terminology (CPT) code indicating ischemic stroke, venous thromboembolism, or \nmyocardial infarction from 7 days before through 30 days after a medical claim indicating a COVID –19 diagnosis.\nVISION: VE of 2 vs. 1 bivalent  doses against COVID- 19-associated \nhospitalization  among immuno competent  adults aged ≥65 years\nSeptember 2022 – September 2023\n• VE estimates adjusted for age, sex, race and ethnicity, geographic region, and calendar time. Updated from: Link -Gelles et al., MMWR, https://www.cdc.gov/mmwr/volumes/72/wr/mm7221a3.htm  \nCDC unpublished datamRNA Dosage PatternTotal\nencountersSARS -CoV-2-\ntest-positive,\nN (%)Median interval\nsince last dose,\ndays (IQR)Adjusted VE\n(95% CI)\nHospitalization,  2 vs. 1 bivalent doses (at least 4 months apart)\n1 bivalent dose (ref) 21,825 1,894 (8) -- Ref\n2 bivalent doses 599 50 (8) 50 (26- 76) 20 (-9 to 41)\n-20 0 20 40 60 80 100\nVaccine  Effectiveness (%)\nVE of an additional bivalent dose at least 4 months after the original bivalent dose appeared to provide some \nprotection, though the confidence interval was wide and crossed 0.\nAge group/2023 -2024 COVID -19 vaccination \nstatus/days since doseTotal\nencountersSARS -CoV-2-\ntest-positive,\nN (%)Median interval since\nlast dose among\nvaccinated, days (IQR) Adjusted VE (95% CI)\n≥18 years\nNo 2023 -2024 COVID -19 dose (ref) 266,148 29,492 (11) 750 (534 -912) Ref\n2023 -2024 COVID -19 dose , 7-299 days earlier 59,366 5,079 (9) 115 (60 -185) 25 (22 to 28)\n2023 -2024 COVID -19 dose , 7-59 days earlier 14,801 1,112 (8) 34 (21 -47) 48 (45 to 52)\n2023 -2024 COVID -19 dose , 60-119 days earlier 16,101 1,338 (8) 88 (73 -103) 28 (23 to 32)\n2023 -2024 COVID -19 dose , 120 -179 days earlier 12,636 766 (6) 147 (133 -163) 17 (10 to 23)\n2023 -2024 COVID -19 dose , 180-299 days earlier 15,828 1,863 (12) 229 (203 -258) -5 (-11 to 1)\n18-64 years\nNo 2023- 2024 COV I D -19 dose (ref) 189,980 19,809 (10) 783 (617 -928) Ref\n2023 -2024 COVID -19 dose , 7-299 days earlier 20,563 1,545 (8) 112 (58 -182) 25 (21 to 29)\n2023 -2024 COVID -19 dose , 7-59 days earlier 5,341 318 (6) 34 (20 -47) 54 (49 to 59)\n2023 -2024 COVID -19 dose , 60-119 days earlier 5,566 366 (7) 88 (74 -104) 32 (25 to 39)\n2023 -2024 COVID -19 dose , 120 -179 days earlier 4,387 227 (5) 147 (133 -163) 16 (4 to 27)\n2023 -2024 COVID -19 dose , 180-299 days earlier 5,269 634 (12) 228 (202 -256) -19 (-30 to -8)\n≥65 years\nNo 2023- 2024 COV I D -19 dose (ref) 76,168 9,683 (13) 661 (431 -860) Ref\n2023 -2024 COVID -19 dose , 7-299 days earlier 38,803 3,534 (9) 116 (61 -187) 25 (22 to 28)\n2023 -2024 COVID -19 dose , 7-59 days earlier 9,460 794 (8) 34 (21 -47) 45 (40 to 49)\n2023 -2024 COVID -19 dose , 60-119 days earlier 10,535 972 (9) 88 (73 -103) 25 (20 to 31)\n2023 -2024 COVID -19 dose , 120 -179 days earlier 8,249 539 (7) 148 (133 -163) 20 (11 to 27)\n2023 -2024 COVID -19 dose , 180-299 days earlier 10,559 1,229 (12) 230 (203 -259) 1 (-7 to 8)VISION: VE of 2023 -2024 COVID -19 vaccine against COVID -19-associated ED/UC \nencounters among immunocompetent adults aged ≥18 years, by age group\nSeptember 2023 – August 2024\nhttps://www.cdc.gov/mmwr/volumes/73/wr/mm7308a5.htm  (Results updated with additional data since publication.) VE was calculated as (1 − odds ratio) x 100%, estimated using a tes t-negative case- control \ndesign, with the odds ratio adjusted for age, sex, race and ethnicity, geographic region, and calendar time. -40 -20 0 20 40 60 80 100\nVISION: VE of 2023- 2024 COVID -19 vaccine against COVID -19-associated \nhospitalization among immunocompetent adults aged ≥18 years, by age group\nSeptember 2023 – August 2024\n*Some estimates are imprecise, which might be due to a relatively small number of persons in each level of vaccination or case  status. This imprecision indicates that the actual VE could be substantially different from the point estimate shown, and estim ates \nshould therefore be interpreted with caution. Additional data accrual could increase precision and allow more precise interpr etation.\nhttps://www.cdc.gov/mmwr/volumes/73/wr/mm7308a5.htm  (Results updated with additional data since publication.) VE was calculated as (1 − odds ratio) x 100%, estimated using a tes t-negative case -control design, adjusted for age, sex, race and ethnicity, \ngeographic region, and calendar time.Age group/2023 -2024 COVID -19 vaccination \nstatus/days since doseTotal\nencountersSARS -CoV-2-\ntest-positive,\nN (%)Median interval since\nlast dose among\nvaccinated, days (IQR) Adjusted VE (95% CI)\n≥18 years\nNo 2023 -2024 COVID -19 dose (ref) 83,596 8,025 (10) 728 (499 -911) Ref\n2023 -2024 COVID -19 dose , 7-299 days earlier 21,468 1,664 (8) 120 (62 -189) 30 (25 to 34)\n2023 -2024 COVID -19 dose , 7-59 days earlier 5,095 382 (8) 34 (21 -47) 50 (44 to 55)\n2023 -2024 COVID -19 dose , 60-119 days earlier 5,623 431 (8) 88 (74 -104) 38 (31 to 44)\n2023 -2024 COVID -19 dose , 120 -179 days earlier 4,754 268 (6) 148 (134 -164) 21 (10 to 31)\n2023 -2024 COVID -19 dose , 180-299 days earlier 5,996 583 (10) 227 (202 -257) -8 (-19 to 3)\n18-64 years\nNo 2023 -2024 COVID -19 dose (ref) 33,335 2,076 (6) 783 (600 -934) Ref\n2023 -2024 COVID -19 dose , 7-299 days earlier 3,694 201 (5) 116 (61 -182) 16 (1 to 28)\n2023 -2024 COVID -19 dose , 7-59 days earlier 903 57 (6) 33 (21 -45) 26 (3 to 44)\n2023 -2024 COVID -19 dose , 60-119 days earlier 999 47 (5) 89 (75 -104) 34 (11 to 51)\n2023 -2024 COVID -19 dose , 120 -179 days earlier 834 26 (3) 148 (135 -164) 28 (-8 to 51)*\n2023 -2024 COVID -19 dose , 180-299 days earlier 958 71 (7) 226 (199 -254) -35 (-76 to -4)*\n≥65 years\nNo 2023 -2024 COVID -19 dose (ref) 50,261 5,949 (12) 692 (460 -890) Ref\n2023 -2024 COVID -19 dose , 7-299 days earlier 17,774 1463 (8) 121 (63 -190) 31 (27 to 36)\n2023 -2024 COVID -19 dose , 7-59 days earlier 4,192 325 (8) 34 (21 -47) 53 (47 to 59)\n2023 -2024 COVID -19 dose , 60-119 days earlier 4,624 384 (8) 88 (74 -104) 38 (30 to 44)\n2023 -2024 COVID -19 dose , 120 -179 days earlier 3,920 242 (6) 148 (134 -164) 19 (7 to 30)\n2023 -2024 COVID -19 dose , 180-299 days earlier 5,038 512 (10) 228 (202 -257) -4 (-16 to 7)\n-80 -60 -40 -20 020 40 60 80 100\nVISION: VE of 2023- 2024 COVID -19 vaccine against COVID -19-associated \nhospitalization and critical illness among adults aged ≥18 years\nSeptember 2023 – August 2024\nAdditional methods, including definition of immunocompromised available: https://www.cdc.gov/mmwr/volumes/73/wr/mm7308a5.htm  (Results updated with additional data since publication.) VE was \ncalculated as (1 − odds ratio) x 100%, estimated using a test -negative case- control design, with odds ratios adjusted for age, s ex, race and ethnicity, geographic region, and calendar time.\n* Some estimates are imprecise, which might be due to a relatively small number of persons in each level of vaccination or ca se status. This imprecision indicates that the actual VE could be substantially \ndifferent from the point estimate shown, and estimates should therefore be interpreted with caution. Additional data accrual could increase precision and allow more precise interpretation. Age group/2023 -2024 COVID -19 vaccination \nstatus/days since doseTotal\nencountersSARS -CoV-2-\ntest-positive,\nN (%)Median interval since\nlast dose among\nvaccinated, days (IQR) Adjusted VE (95% CI)\n≥18 years, hospitalization\nNo 2023 -2024 COVID -19 dose (ref) 83,596 8,025 (10) 728 (499 -911) Ref\n2023 -2024 COVID -19 dose , 7-299 days earlier 21,468 1,664 (8) 120 (62 -189) 30 (25 to 34)\n2023 -2024 COVID -19 dose , 7-59 days earlier 5,095 382 (8) 34 (21 -47) 50 (44 to 55)\n2023 -2024 COVID -19 dose , 60-119 days earlier 5,623 431 (8) 88 (74 -104) 38 (31 to 44)\n2023 -2024 COVID -19 dose , 120 -179 days earlier 4,754 268 (6) 148 (134 -164) 21 (10 to 31)\n2023 -2024 COVID -19 dose , 180-299 days earlier 5,996 583 (10) 227 (202 -257) -8 (-19 to 3)\n≥18 years, critical illness\nNo 2023 -2024 COVID -19 dose (ref) 76,965 1,394 (2) 730 (503 -913) Ref\n2023 -2024 COVID -19 dose , 7-299 days earlier 20,010 206 (1) 119 (62 -187) 50 (42 -58)\n2023 -2024 COVID -19 dose , 7-59 days earlier 4,758 45 (1) 34 (21 -46) 67 (55 -75)\n2023 -2024 COVID -19 dose , 60-119 days earlier 5,248 56 (1) 89 (74 -104) 56 (42 -67)\n2023 -2024 COVID -19 dose , 120 -179 days earlier 4,523 37 (1) 149 (134 -164) 40 (16 -58)\n2023 -2024 COVID -19 dose , 180-299 days earlier 5,481 68 (1) 226 (201 -256) 21 (-3-40)\n-80 -60 -40 -20 020 40 60 80 100\nOutcome Analysis Vaccine effectiveness, % (95% CI)\nThromboembolic events* Medicare, ESKD adults ≥65y, 2023- 2024 vaccine, median follow -up days=74 53 (23 -71)\nDeath Medicare, E SK D adults ≥65y , 2023- 2024 vaccine, med ian follow -up days=104 47 (15 -67)\nICU admission/deathV ISION, adults ≥65y, 2023- 2024 vaccine, med ian follow -up days=34 69 (57 -78)\nV ISION, adults ≥65y, 2023- 2024 vaccine, med ian follow -up days=89 56 (42 -68)\nV ISION, adults ≥65y, 2023- 2024 vaccine, med ian follow -up days=149 43 (18 -60)Effectiveness of 2023- 2024 COVID -19 vaccines against COVID -19-associated critical \noutcomes in immunocompetent adults ≥65 years, Medicare and VISION data\nCDC unpublished data. Medicare analysis includes only Medicare fee -for-service beneficiaries.0 20 40 60 80 100 Abbreviations: ESKD = end stage kidney disease; y = years; IMV = invasive mechanical ventilation; ICU = intensive care unit\n*A COVID -19–related thromboembolic event was defined as presence of an International Classification of Disease, 10th \nEdition  (ICD -10) or common procedural terminology (CPT) code indicating ischemic stroke, venous thromboembolism, or \nmyocardial infarction from 7 days before through 30 days after a medical claim indicating a COVID –19 diagnosis.\n•VE findings should be interpreted as the added benefit provided by COVID -19 vaccination in a population with a \nhigh prevalence of vaccine - and infection- induced immunity at the start of the 2023- 2024 respiratory virus season.\n•2023- 2024 COVID -19 vaccination provided increased protection against COVID -19-associated ED/UC visits and \nhospitalizations compared to no 2023- 2024 vaccine dose.\n-Protection waned to 0 against COVID -19-associated ED/UC visits and hospitalization by ~4 -6 months.\n•Waning patterns of 2023- 2024 COVID -19 vaccines appeared similar to previous COVID -19 vaccine formulations; \nmost durable protection appeared to be for critical illness\n-VE against critical illness remained above 40% at 5 months after vaccination among those ≥65 years\n•As with previous COVID -19 vaccine formulations, effectiveness was similar across age groups\n•Data from prior seasons show that an additional dose of the same formula appeared to provide additional \nprotection.  Conclusions: COVID- 19 VE in adults ≥65 years\nAcknowledgements \nCDC\nAmanda B. Payne\nKatherine E. Fleming -Dutra\nLakshmi PanagiotakopoulosLauren Roper\nAmadea Britton\nAllison CieslaFatimah Dawood\nJennifer DeCuir\nMonica Dickerson\nSascha Ellington\nShikha GargAmber Kautz\nNathaniel M. Lewis\nKevin Ma\nJosephine Mak\nJoe MillerMorgan Najdowski\nZach Smith\nDiya Surie\nCaitlin Ray\nRyan WiegandVISION Collaborators\nWestatSarah Ball\nAngela Cheung\nMargaret Dunne\nPatrick Mitchell\nSarah ReeseElizabeth Rowley\nJanet Watts\nZack Weber\nIntermountain Health\nKristin Dascomb\nKaiser Permanente Center for Health Research\nStephanie A. Irving\nKaiser Permanente Northern California\nNicola P. Klein\nRegenstrief\nShaun J. Grannis\nUniversity of Colorado\nToan C. Ong\nHealthPartners\nMalini B. DeSilva\nColumbia University\nKarthik NatarajanIVY Collaborators\nCristie  Columbus\nLaurence W. Busse\nSteven Y. Chang\nAbhijit Duggal\nMatthew C. Exline\nManjusha GaglaniKevin W. Gibbs\nAdit A. Ginde\nDavid N. HagerEstelle S. Harris\nCassandra JohnsonNicholas J. Johnson\nAkram Khan\nJennie H. KwonAdam S. Lauring\nChristopher MallowEmily MartinAmira MohamedNicholas M. Mohr\nJarrod M. Mosier\nIthan  D. Peltan\nMatthew Prekker\nBasmah  Safdar\nWesley H. SelfNathan I. Shapiro\nJay S. Steingrub\nIvana A. Vaughn\nJennifer G. Wilson\nYuwei Zhu\nCMS Collaborators\nCMS\nAlia Bayatti\nAcumenHeng -Ming Sung\nIvy Zhang\nCarla Gomez Victor\nYenlin  Lai\nBradley LufkinYoganand Chillarige\n+ many more!", "summary": "Effectiveness of COVID -19 vaccines  Ruth Link -Gelles, PhD, MPH CDR, US Public Health Service Vaccine Effectiveness Program LeadCoronavirus and Other Respiratory Viruses DivisionCenters for Disease Control and Prevention October 23, 2024National Center for Immunization and Respiratory Diseases   •VE data to inform need for: -Additional doses in immunocompromised •What’s known about VE in immunocompromised vs. non- immunocompromised adults, including waning by time since dose -Additional dose…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-23-24-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/04-COVID-Link-Gelles-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 30}
{"title": "05 COVID Prosser 508", "content": "Economic analysis of an \nadditional dose of the \n2024 -2025 COVID -19 vaccine\nUniversity of Michigan \nCOVID -19 Vaccination Modeling Team\nPresentation to the Advisory Committee on Immunization Practices\nOctober 23, 2024\n1\nStudy team\nUniversity of Michigan\n•Lisa A. Prosser, PhD, Principal Investigator\n•David W. Hutton, PhD, Co -Investigator\n•Acham Gebremariam, MS, Programmer/Analyst\n•Angela Rose, MS, MPH, Project Manager\n•Kerra Mercon, MS, Research Assistant\nWake Forest University\n•Cara Janusz, PhDCenters for Disease Control and Prevention\n•Jamie Pike, PhD, Health Economist, Project officer\n•Megan Wallace, DrPH, Epidemiologist\n•Ismael Ortega -Sanchez, PhD, Senior Economist\n•Andrew Leidner, PhD, Economist\n•Fangjun Zhou, PhD, Health Scientist\n•Melisa Shah, MD, MPH, Medical Epidemiologist \n•Danielle Moulia, MPH, Health Scientist \n•Ruth Link -Gelles, PhD, Epidemiologist\n•Sharon Saydah, PhD, Epidemiologist\n2\nConflict of interest statement\n3Authors have no known conflicts of interest. \nObjectives\n•Original aims*:\noEstimate annual disease burden and healthcare utilization associated with COVID -19 \nillness and COVID- 19 booster vaccination, including cases of symptomatic illness, \nhospitalizations, deaths, adverse events, costs, and quality- adjusted life years\noProject cost- effectiveness of an updated mRNA booster against COVID -19-associated \nillness in persons ages ≥18 years\n•Update s to the current version of the model (Phase 3B): \no2-dose strategy (an additional mid- year dose)\no2023- 2024 hospitalization rates (COVID- NET data)\noVaccine dose costs reflect CDC -negotiated 2024- 2025 prices\noAll cost inputs adjusted to 2024$\n4* Earlier analyses from this model were presented to ACIP in September 2023, February 2024, and June 2024: Prosser, Lisa A. (2023). Economic Analysis of Vaccination \nwith mRNA Booster Dose against COVID -19 Among Adults; Prosser, Lisa A (2024). Economic analysis of an additional dose of COVID -19 vaccine; Prosser, Lisa A (2024). \nEconomic Analysis of COVID -19 Vaccination.\nWeekly rates of \nCOVID -19 \nassociated \nhospitalizations \nby season, all \nages\n52021- 2022\n2020- 2021\n2019- 2020\n2023- 20242022- 2023Hospitalization rate per 100,000\nOct       Nov       Dec      Jan        Feb      Mar       Apr      May      Jun       Jul      Aug      Sep \n40\n30\n20\n10\n0Input data for Phase 3b model\nSource: COVID -NET\nProbability of hospitalization due to COVID -19 illness\nAge groups 2023- 2024 2022- 2023 % change\n5-11 years 0.000105 0.000133 -21%\n12-17 years 0.000139 0.000181 -23%\n18-49 years 0.000299 0.000443 -33%\n50-64 years 0.001184 0.001551 -24%\n>65 years 0.006778 0.007901 -14%\n6Source: COVID -NET\nUpdated seasonality -adjusted vaccine impact*\nHealth outcomes AgeSeasonality -adjusted vaccine impact\n1-dose strategy 2-dose strategy\nBase case Low High Base case Low High\n•Symptomatic illness (non -\nhospitalized)\n•Hospitalization, \nuncomplicated5-11 y 0.375 0.112 0.705 0.512 0.158 0.716\n12-17 y 0.379 0.110 0.704 0.501 0.143 0.711\n18-49 y 0.295 0.106 0.442 0.404 0.144 0.482\n50-64 y 0.310 0.118 0.453 0.416 0.157 0.492\n>65 y 0.315 0.121 0.455 0.422 0.163 0.498\n•Critical illness**\n•Death5-11 y 0.375 0.112 0.705 0.512 0.158 0.716\n12-17 y 0.379 0.110 0.704 0.501 0.143 0.711\n18-49 y 0.391 0.221 0.662 0.527 0.355 0.666\n50-64 y 0.402 0.234 0.665 0.534 0.366 0.670\n>65 y 0.410 0.238 0.665 0.536 0.369 0.671\nSource: COVID -NET, VISION, and IVY* Updated hospitalization rates Oct 23 - Sept 24\n**Hospitalization requiring ICU and/or ventilator assistance7\nSeasonality -adjusted vaccine impact, \n2023 -2024 v. 2024 -2025\nAge group 1-dose 2-dose\nSeasonality -adjusted vaccine impact against symptomatic illness or hospitalization\n5-11 years -11% -1%\n12-17 years -10% -6%\n18-49 years -18% -6%\n50-64 years -13% -5%\n65+ years -9% -3%\nSeasonality -adjusted vaccine impact against critical care (hospitalization with ICU stay or death)\n5-11 years -11% -1%\n12-17 years -10% -6%\n18-49 years -15% -3%\n50-64 years -12% -3%\n65+ years -9% -2%\n8\nVaccine dose cost, 2023 -2024 v. 2024 -2025\n92023 2024\n% \nchange CDCPrivate \nsector % VFC or \nBridgeBase \ncaseCDC  Private \nsector% VFC or \nBridgeBase \ncase\n5-11 y\nPfizer $65.45 $77.0050% $89.09$65.45 $77.0054% $88.25 -1%Moderna $85.91 $128.00 $85.91 $129.00\n12-17 y\nPfizer $97.75 $115.0050% $102.44$99.71 $136.7554% $114.18 10%Moderna $85.91 $128.00 $85.91 $141.80\n18+ y\nPfizer $97.75 $115.0012.8% $118.73$99.71 $136.75NA $139.28 15%Moderna $85.91 $128.00 $85.91 $141.80\nSource: CDC Vaccine Price List\nAdditional assumptions: 2 -dose strategy\n•Adverse events: Twice the number of the 1 -dose strategy\n•Costs of vaccination: Twice the cost of the 1 -dose strategy\n•See additional slides\n10\nAnalysis Plan\n•Conduct base case and uncertainty analyses (one -way sensitivity and scenario \nanalyses) comparing no vaccination, 1 -dose, and 2 -dose strategies\n•Project disaggregated outcomes stratified by intervention strategy and by age \nsubgroups (5 -11y, 12- 17y, 18- 49y, 50- 64y, >65y) – supplemental slides\noCases\noHospitalizations\noICU\noLong COVID\noDeaths\noCosts\noQALYs\noAdverse events\n***This presentation reports preliminary results from the fourth phase of an ongoing analysis***\n11\n•Multi -way sensitivity analyses/parameter sets\noVaccination -related costs\noVaccination settings\noHospitalization and critical illness\n•Scenario analyses\noSeasonality adjusted vaccine impact\noAlternative seasonality scenarios\noProbability of hospitalization - proxy for lower and higher risk cohorts\noProbability of critical care - proxy for higher risk cohorts\noProbability of symptomatic illness\noVaccine dose cost\n•One-way sensitivity analyses\n12Analysis Plan cont.: Uncertainty analyses\nResults\n13\nDisaggregated results, per 100,000, societal perspective, \n2024 -2025 vaccination, preliminary results\n1405,00010,00015,00020,00025,00030,00035,00040,000\n5-11 y 12-17 y 18-49 y 50-64 y ≥65 y# Events\n0100200300400500600\n5-11 y 12-17 y 18-49 y 50-64 y ≥65 y# Long COVID\n0100200300400500600700800\n5-11 y 12-17 y 18-49 y 50-64 y ≥65 y# Hospitalizations\n0102030405060708090100\n5-11 y 12-17 y 18-49 y 50-64 y ≥65 y# ICU stays\n0510152025303540\n5-11 y 12-17 y 18-49 y 50-64 y ≥65 y# Deaths\nNote: Height of bars represents total outcomes without vaccination\n\nDisaggregated results, per 100,000, societal perspective, 2024 -2025 \nvaccination, preliminary results\nAge Intervention strategyOutcomes Outcomes Averted\nCasesLong \nCOVIDHosp. ICU Deaths CasesLong \nCOVIDHosp. ICU Deaths\n5-11 yNo vaccination 31,450 70.6 10.5 2.2 0.1 - - - - -\nVaccination, 1 -dose 19,656 44.1 6.6 1.3 0.1 11,794 26.5 3.9 0.8 0.0\nVaccination, 2 -dose 15,348 34.4 5.1 1.1 0.0 4,309 9.7 1.4 0.3 0.0\n12-17 yNo vaccination 31,450 71.5 13.9 2.9 0.1 - - - - -\nVaccination, 1 -dose 19,530 44.4 8.6 1.8 0.1 11,919 27.1 5.3 1.1 0.0\nVaccination, 2 -dose 15,694 35.7 6.9 1.4 0.1 3,837 8.7 1.7 0.4 0.0\n18-49 yNo vaccination 31,450 413.0 29.9 3.9 0.4 - - - - -\nVaccination, 1 -dose 22,172 299.1 21.1 2.4 0.2 9,278 121.8 8.8 1.5 0.2\nVaccination, 2 -dose 18,744 246.1 17.8 1.8 0.2 3,428 45.0 3.3 0.5 0.1\n50-64 yNo vaccination 28,410 395.4 118.0 22.8 3.8 - - - - -\nVaccination, 1 -dose 19,603 272.8 81.4 13.6 2.3 8,807 122.6 36.6 9.2 1.5\nVaccination, 2 -dose 16,591 230.9 68.9 10.6 1.9 3,011 41.9 12.5 3.0 0.5\n>65 yNo vaccination 33,390 498.2 678.0 90.9 34.4 - - - - -\nVaccination, 1 -dose 22,872 341.3 464.4 53.6 21.4 10,518 156.9 213.6 37.3 12.9\nVaccination, 2 -dose 19,299 288.0 391.9 42.2 17.3 3,573 53.3 72.6 11.5 4.1\n15\nIncremental cost -effectiveness ratios (ICERs), per 1000,\nsocietal perspective, 2024 -2025 vaccination, preliminary results  \nAge group Intervention strategy Projected costsIncremental\ncostsProjected \nQALYsIncremental \nQALYsICER\n($/QALY)\n5-11 yNo vaccination $39,723 - 26,788 - -\nVaccination, 1 -dose $191,776 $152,053 26,789 0.6566 $231,570\nVaccination, 2 -dose $353,283 $161,507 26,789 0.2129 $758,268\n12-17 yNo vaccination $46,010 - 24,638 - -\nVaccination, 1 -dose $214 ,115 $168,105 24,639 0.6733 $249,670\nVaccination, 2 -dose $394,045 $179,930 24,639 0.1942 $926,390\n18-49 yNo vaccination $128,351 - 20,208 - -\nVaccination, 1 -dose $289,206 $160,855 20,209 0.4802 $335,010\nVaccination, 2 -dose $474,497 $185,290 20,209 0.1633 $1,134,840\n50-64 yNo vaccination $218,703 - 12,278 - -\nVaccination, 1 -dose $347,499 $128,796 12,279 0.6197 $207,834\nVaccination, 2 -dose $523,448 $175,949 12,279 0.1957 $898,653\n>65 yNo vaccination $336,230 - 6,525 - -\nVaccination, 1 -dose $419,404 $83,174 6,527 1.4132 $58,855\nVaccination, 2 -dose $577,132 $157,729 6,528 0.4424 $356,534\n16 ICER = incremental cost effectiveness ratio; QALY = quality- adjusted life year  \nIncremental cost -effectiveness ratios (ICERs), adding a 2 -dose \nstrategy, societal perspective, 2024 -2025 vaccination,  \npreliminary results \nAge group Intervention strategy ICER ($/QALY)\n5-11 yNo vaccination -\nVaccination, 1 -dose $231,570\nVaccination, 2 -dose $758,268\n12-17 yNo vaccination -\nVaccination, 1 -dose $249,670\nVaccination, 2 -dose $926,390\n18-49 yNo vaccination -\nVaccination, 1 -dose $335,010\nVaccination, 2 -dose $1,134,840\n50-64yNo vaccination -\nVaccination, 1 -dose $207,834\nVaccination, 2 -dose $898,653\n>65 yNo vaccination -\nVaccination, 1 -dose $58,855\nVaccination, 2 -dose $356,534\n17 QALY = quality -adjusted life year\n$0 $50,000 $100,000 $150,000 $200,000 $250,000Productivity loss due to Long COVID (0.25, 1)Cost of nirmatrelvir-r ($0, $1494)Probability of outpatient visit given symptomatic COVID-19 (0.1996, 0.3088)Time spent to receive vaccine, physician office setting (0.17, 2)Lifetime productivity loss ($189191, $378382)(Quality adjustment for symptomatic COVID-19 (0.0018, 0.0074)Probability of symptomatic COVID-19 (0.2312, 0.451)Cost of vaccine dose ($30, $140)Probability of hospitalization (0.00235, 0.0209)SAVI*\n$/QALY1-way sensitivity analyses, 1 -dose strategy, >65 y\n18Note: Numbers in parenthesis indicate range of input values\n* Seasonality adjusted vaccine impact (SAVI) against hospitalization 1 -dose: 0.121, 0.455; SAVI against critical illness 1- dose:  0.238, 0.665\nQALY = quality -adjusted life year; ICER = incremental cost effectiveness ratio; SAVI = seasonality -adjusted vaccine impact; CS =  cost-saving\nCS\nCS\nBase case: $58,855\n1-way sensitivity analyses, 2 -dose strategy, >65 y\n19Note: Numbers in parenthesis indicate range of input values\n* Seasonality adjusted vaccine impact (SAVI) against hospitalization 2 -dose: 0.163, 0.498; SAVI against critical illness 2- dose:  0.369, 0.671\nQALY = quality -adjusted life year; ICER = incremental cost effectiveness ratio; SAVI = seasonality -adjusted vaccine impact\nBase case: $356,534 $0 $500,000 $1,000,000 $1,500,000 $2,000,000Probability of death given ICU, no ventilator (0.105, 0.162)Probability of death given ICU with ventilator (0.466, 0.599)Probability of systemic reaction (0.107, 0.171)Quality adjustment for systemic reaction (0.0001, 0.0004)Time spent to receive vaccine, physician office setting (0.17, 2)Probability of symptomatic COVID-19 illness (0.2312, 0.451)Quality adjustment for symptomatic COVID-19 (0.0018, 0.0074)Cost of vaccine dose ($30, $140)Probability of hospitalization given symptomatic COVID-19 (0.00235, 0.0209)SAVI *\n$/QALY\nICERs, 1 -way sensitivity analysis, probability of \nhospitalization, societal perspective, 2024 -2025 vaccination,  \npreliminary results\n*Probability of hospitalization inputs, base case (range):  5-11 y: 0.000105 (0.0000168 - 0.000336); 12-  17 y: 0.000139 (0.0000252 - 0.000456);\n18-49 y: 0.000299 (0.0000799 - 0.00204); 50-64 y: 0.00118 (0.000348 - 0.00479); >65 y  0.00678 (0.00235 - 0.02090)\nICER = incremental cost -effectiveness ratio; QALY = quality- adjusted life yearAge group Intervention strategyICER ($/QALY)\nBase case Lower bound Upper bound\n5-11 yVaccination, 1 -dose $231,570 $237,799 $216,062\nVaccination, 2 -dose $758,268 $773,808 $719,816\n12-17 yVaccination, 1 -dose $249,670 $256,907 $230,464\nVaccination, 2 -dose $926,390 $944,391 $878,879\n18-49 yVaccination, 1 -dose $335,010 $363,084 $183,058\nVaccination, 2 -dose $1,134,840 $1,207,451 $746,171\n50-64 yVaccination, 1 -dose $207,834 $309,213 $29,782\nVaccination, 2 -dose $898,653 $1,208,636 $373,246\n>65 yVaccination, 1 -dose $58,855 $163,421 Cost saving\nVaccination, 2 -dose $356,534 $682,429 $99,455\n20\nICER, scenario analysis varying probability of hospitalization, \nsocietal perspective, 2024 -2025 vaccination, \npreliminary results  \n21Age \ngroupIntervention strategyICER ($/QALY)\n¼ base case ½ base case Base case 2x base case 3x base case 4x base case\n5-11 yVaccination, 1 -dose $237,123 $235,256 $231,570 $224,381 $217,426 $210,693\nVaccination, 2 -dose $772,119 $767,458 $758,268 $740,400 $723,184 $706,585\n12-17 yVaccination, 1 -dose $256,292 $254,067 $249,670 $241,081 $232,755 $224,680\nVaccination, 2 -dose $942,860 $937,321 $926,390 $905,095 $884,525 $864,645\n18-49 yVaccination, 1 -dose $363,779 $353,853 $335,010 $300,917 $270,898 $244,263\nVaccination, 2 -dose $1,209,252 $1,183,547 $1,134,840 $1,046,999 $969,960 $901,847\n50-64 yVaccination, 1 -dose $317,597 $274,393 $207,834 $121,533 $68,015 $31,582\nVaccination, 2 -dose $1,234,636 $1,101,255 $898,653 $641,036 $484,085 $378,439\n>65 yVaccination, 1 -dose $192,897 $127,480 $58,855 $1,483 Cost saving Cost saving\nVaccination, 2 -dose $775,607 $569,600 $356,534 $180,751 $103,912 $60,824\nAdjusted risk of hospitalization by underlying condition: hypertension: 2.8, coronary artery disease: 1.3, history of stroke:  0.9, diabetes: 3.2, obesity: 2.9, \nsevere obesity: 4.4, chronic kidney disease: 4.0, asthma: 1.4, chronic obstructive pulmonary disease: 0.9 . Ko et al 2021. \nICER = incremental cost effectiveness ratio; QALY = quality- adjusted life year  \nICER, scenario analysis varying probability of hospitalization*, \nage >65, societal perspective, 2024 -2025 vaccination,\npreliminary results\n22Age \ngroupIntervention strategyICER ($/QALY)\n¼ base case\n(169 per \n100,000)½ base case\n(339 per \n100,000)Base case\n(678 per \n100,000)2x base case\n(1356 per \n100,000)3x base case\n(2033 per \n100,000)4x base case\n(2711 per \n100,000)\n>65 yVaccination, 1 -dose $192,897 $127,480 $58,855 $1,483 Cost saving Cost saving\nVaccination, 2 -dose $775,607 $569,600 $356,534 $180,751 $103,912 $60,824\n*Adjusted risk of hospitalization by underlying condition: chronic obstructive pulmonary disease: 0.9, history of stroke: 0.9 , coronary artery \ndisease: 1.3, asthma: 1.4, hypertension: 2.8, obesity: 2.9, diabetes: 3.2, chronic kidney disease: 4.0, severe obesity: 4.4. Ko et al 2021.\nICER = incremental cost -effectiveness ratio; QALY = quality- adjusted life year\nICER, scenario analysis varying probability of critical care, \nsocietal perspective, 2024 -2025 vaccination, \npreliminary results  \n23Age group Intervention strategyICER ($/QALY)\nBase case* 2x 3x 4x\n5-11 yVaccination, 1 -dose $231,570 $226,638 $221,839 $217,169\nVaccination, 2 -dose $758,268 $744,568 $731,285 $718,401\n12-17 yVaccination, 1 -dose $249,670 $245,073 $240,586 $236,205\nVaccination, 2 -dose $926,390 $912,162 $898,312 $884,826\n18-49 yVaccination, 1 -dose $335,010 $310,742 $288,947 $269,266\nVaccination, 2 -dose $1,134,840 $1,066,161 $1,004,627 $949,177\n50-64 yVaccination, 1 -dose $207,834 $146,192 $105,154 $75,870\nVaccination, 2 -dose $898,653 $692,143 $556,444 $460,466\n>65 yVaccination, 1 -dose $58,855 $28,898 $12,731 $2,614\nVaccination, 2 -dose $356,534 $239,110 $175,202 $135,015\n*Base case probability of  ICU given hospitalization: 5 -11 y - 0.205; 12- 17 y - 0.208; 18- 49 y -  0.130; 50- 64 y - 0.193, >65 y - 0.134\nAdjusted risk ratios for ICU: 1 condition: 1.32, 2- 5 conditions: 1.60, 6- 10 conditions: 1.84, >10 conditions: 1.96. Underlying c onditions: Essential hypertension, \nDisorders of lipid metabolism, Obesity, Diabetes with complication, Coronary atherosclerosis and other heart disease, Esophag eal disorders, Chronic kidney disease, \nAnxiety and fear -related disorders, COPD and bronchiectasis, Thyroid disorders, Depressive disorders, Implant device or graft -related encounter, Sleep -wake \ndisorders, Neurocognitive disorders, Osteoarthritis, Aplastic anemia, Diabetes without complication, Asthma. Source: Kompaniyets  et al 2021.\nICER = incremental cost effectiveness ratio; QALY = quality -adjusted life year  \nScenario analysis: vaccination -related costs, societal \nperspective, 2024 -2025 vaccination, preliminary results  \nAge group Intervention strategyICER ($/QALY)\nBase case All lower All upper\n5-11 yVaccination, 1 -dose $231,570 $103,396 $353,999\nVaccination, 2 -dose $758,268 $363,134 $1,135,689\n12-17 yVaccination, 1 -dose $249,670 $92,955 $325,103\nVaccination, 2 -dose $926,390 $383,118 $1,187,889\n18-49 yVaccination, 1 -dose $335,010 $71,945 $382,665\nVaccination, 2 -dose $1,134,840 $361,230 $1,274,981\n50-64 yVaccination, 1 -dose $207,834 $4,019 $244,737\nVaccination, 2 -dose $898,653 $253,551 $1,015,457\n>65 yVaccination, 1 -dose $58,855 Cost saving $75,585\nVaccination, 2 -dose $356,534 $70,458 $409,976\nICER = incremental cost effectiveness ratio; QALY = quality- adjusted life year  \nICER, scenario analyses varying vaccination costs, \nage >65, societal perspective, 2024 -2025 vaccination,\npreliminary results\nAge \ngroupIntervention strategyICER ($/QALY)\n$20 $60 $80 $100Base case\n$133 \n>65 yVaccination, 1 -dose Cost saving $2,755 $16,908 $31,060 $58,855\nVaccination, 2 -dose $86,910 $177,327 $222,536 $267,744 $356,534Age group Intervention strategyICER ($/QALY)\nAll lower Base case All upper\n>65 yVaccination, 1 -dose Cost saving $58,855 $75,585\nVaccination, 2 -dose $70,458 $356,534 $409,976\nVarying vaccine dose cost onlyVarying all vaccination -related costs*\n25*Multi -way sensitivity analysis varying vaccine dose cost, vaccine administration cost, time costs of vaccination, and cost of  \nvaccine -associated adverse events to lower and upper bounds. See supplementary slide 44 for input data.\nICER = i ncremental  cost-effectiveness ratio; QALY = quality- adjusted life year\nScenario analysis: vaccine dose cost, 2024 -2025 \nvaccination, preliminary results  \n$0$200,000$400,000$600,000$800,000$1,000,000$1,200,000\n$20 $30 $40 $50 $60 $70 $80 $90 $100 $110 $120 $130 $140$114$88\n$0$200,000$400,000$600,000$800,000$1,000,000$1,200,000\n$20 $30 $40 $50 $60 $70 $80 $90 $100 $110 $120 $130 $140$114$881-dose 2-dose\n$139\nCost per dose Cost per dose$/QALY\n$/QALY\nNote: arrows indicate base case vaccine dose cost by age group\nQALY= quality -adjusted life year$139$139$139\n$139\n$139\nLimitations\n•Unpublished data used to derive key parameters in the model: vaccine effectiveness, \nsymptomatic illness, probabilities of hospitalization and critical illness\n•Data sources vary in representativeness, generalizability\n•VE estimates derived from single prior season data \n•Few seasons to date to estimate seasonality\n•MarketScan  data for ages >65 only includes those with supplemental insurance\n•Evidence base for long covid is especially scarce\n•Model does not include reduced transmission (conservative approach) \n27\nSummary\n2024- 2025 COVID -19 vaccination, 2 -dose strategy\n•ICERs for age groups <65 y were less favorable than for those > 65 y across \nplausible parameter ranges\n•For >65 years, ICERs are sensitive to seasonality -adjusted vaccine impact, \nprobability of hospitalization, and costs of vaccination\n•ICERs are more favorable in scenarios with higher risk of hospitalization and \nlower costs of vaccination\n28", "summary": "Economic analysis of an  additional dose of the  2024 -2025 COVID -19 vaccine University of Michigan  COVID -19 Vaccination Modeling Team Presentation to the Advisory Committee on Immunization Practices October 23, 2024 1 Study team University of Michigan •Lisa A. Prosser, PhD, Principal Investigator •David W. Hutton, PhD, Co -Investigator •Acham Gebremariam, MS, Programmer/Analyst •Angela Rose, MS, MPH, Project Manager •Kerra Mercon, MS, Research Assistant Wake Forest University •Cara Janusz,…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-23-24-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/05-COVID-Prosser-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 28}
{"title": "06 COVID Roper 508", "content": "Evidence to Recommendations Framework:\nAdditional Doses of 2024– 2025 COVID -19 Vaccine in Older Adults and \nPeople with Moderate or Severe Immunocompromise  \nMs. Lauren Roper, MPH\nCOVID -19 ACIP Work Group co -lead\nAdvisory Committee on Immunization Practices Meeting\nOctober 23, 2024National Center for Immunization and Respiratory Diseases \n\n•On June 27, 2024, ACIP voted to recommend 2024 –2025 COVID -19 \nvaccines for everyone ages 6 months and older \n•On August 22, 2024, FDA approved and authorized 2024 –2025 Pfizer -\nBioNTech and Moderna COVID -19 vaccines* for people ages 6 months and \nolder \n•On August 30, 2024, FDA authorized 2024 –2025 Novavax COVID -19 \nvaccine** for people aged 12 years and olderACIP recommendations for COVID -19 vaccines\nFDA: Food and Drug Administration\n* Omicron JN.1 lineage, KP .2 strain** Omicron JN.1 lineage, JN.1 strain2\nIn addition to previously recommended 2024– 2025 vaccination:\n•Should a second dose* of 2024– 2025 COVID -19 vaccine be recommended for adults \nages 65 years and older?\n•Should a second dose** of 2024– 2025 COVID -19 vaccine be recommended for \npeople ages 6 months and older who are moderately or severely \nimmunocompromised?\n•Should additional doses (i.e., 3 or more) of 2024– 2025 COVID -19 vaccine be \nrecommended for people ages 6 months and older who are moderately or severely \nimmunocompromised under shared clinical decision -making ?Evidence to Recommendations ( EtR) Framework\nPolicy Questions\n*If previously unvaccinated and receiving Novavax, 2 doses are recommended as initial vaccination series followed by a third dose of any age -appropriate 2024 -\n2025 COVID -19vaccine 6 months (minimum interval 2 months) after second dose​.\n**If previously unvaccinated or receiving initial vaccination series, at least 2 doses of 2024 –2025 vaccine are recommended, and depending on vaccination \nhistory more may be needed. This additional 2024– 2025 vaccine dose is recommended 6 months (minimum interval 2 months) after com pletion of initial \nvaccination series.​3\nSept – Nov \n2021 COVID -19 \nvaccine \nbooster doses \nrecommended \nfor persons \nages ≥18 years\nMay 2022 Additional  \nCOVID -19 vaccine \nbooster dose \nrecommended for \npersons ages ≥50 \nyears\nSept – Oct \n2022 Bivalent \nCOVID -19 \nvaccine dose \nrecommended \nfor persons \nages ≥5 years\nApril \n2023 Optional additional \nbivalent COVID -19 \nvaccine dose \nrecommended for \npersons ages ≥65 \nyears (under SCDM)\nSept \n20232023– 2024 \nCOVID -19 vaccine \ndoses \nrecommended \nfor persons ages \n≥6 monthsAdditional 2023 –\n2024 COVID -19 \nvaccine dose \nrecommended for \npersons ages ≥65 \nyears2024– 2025 \nCOVID -19 \nvaccine doses \nrecommended \nfor persons ages \n≥6 months\nFeb 2024 June 2024 Older adults: timeline of additional COVID -19 vaccine dose \nrecommendations\nSCDM: Shared clinical decision -making 4\n•2024– 2025 COVID -19 vaccine dose is recommended at least 2 months after receipt of the \nlast COVID -19 vaccine dose​\n•mRNA COVID -19 vaccines authorized or approved for ages 6 months and older and \nNovavax COVID -19 vaccine authorized for ages 12 years and older​\n•People who are previously unvaccinated for COVID -19 and are receiving Novavax should \ncomplete a 2 -dose initial seriesCurrent  recommendations for people ages 5 years and older \nDoses recommended:\n•1 dose of 2024– 2025 COVID -19 vaccine\n5\nPeople with moderate or severe immunocompromise: ACIP \nrecommendations for additional COVID -19 vaccine doses\nOct/Nov 2021 Additional COVID -19 vaccine \nbooster dose recommended \nfor people with moderate or \nsevere immunocompromise\nApril 2022 Optional 2nd booster \ndose of mRNA ≥ 4 \nmonths after 1st booster \n(under SCDM)\nApril 2023 Optional additional bivalent mRNA dose \nfor people with immunocompromise who \nhave already received a bivalent mRNA \ndose, at least 2 months after initial \nbivalent mRNA dose (under SCDM)\nAdditional bivalent mRNA doses as \nneeded, at 2-month intervals at the \ndiscretion of the healthcare provider \n(under SCDM)\nhttps://www.sciencedirect.com/science/article/pii/S0264410X23014664?via%3Dihub\nhttps://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2023- 04-19/06- COVID -Oliver -508.pdf\nhttps://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2023- 04-19/07- COVID -Twentyman -508.pdf  SCDM: Shared clinical decision -making\n6\nCurrent  recommendations for people ages 6 months and older \nwho are moderately or severely immunocompromised\nDoses recommended:\nInitial COVID -19 vaccine series*\nAt least 1 2024– 2025 COVID -19 vaccine dose\nMay receive 1 additional 2024 –2025 COVID -19 \nvaccine dose with option for further additional \ndoses of 2024– 2025 COVID -19 vaccine**\n*Series of 3 homologous mRNA COVID -19 vaccine doses or 2 Novavax COVID -19 vaccine doses (if ages 12 years and older); includes r evaccination after \nhematopoietic cell transplant and CAR -T-cell, or B -cell- depleting therapies. ​\n**Further additional dose(s) may be administered, informed by the clinical judgement of a healthcare provider and personal pr eference and \ncircumstances. Further additional doses should be administered at least 2 months after the last 2024 -2025 COVID -19 vaccine dose.  \nFor more information, see https://www.cdc.gov/vaccines/covid -19/clinical -considerations/interim- considerations -us.html#immunocompromised .​\n7\nIn addition to previously recommended 2024– 2025 vaccination:\n•Should a second dose* of 2024– 2025 COVID -19 vaccine be recommended \nfor adults ages 65 years and older?\n•Should a second dose** of 2024– 2025 COVID -19 vaccine be recommended \nfor people ages 6 months and older who are moderately or severely \nimmunocompromised?\n•Should additional doses (i.e., 3 or more) of 2024– 2025 COVID -19 vaccine be \nrecommended for people ages 6 months and older who are moderately or severely immunocompromised under shared clinical decision- making ?Evidence to Recommendations ( EtR) Framework\nPolicy Questions\n*If previously unvaccinated and receiving Novavax, 2 doses are recommended as initial vaccination series followed by a third dose of any age -\nappropriate 2024 -2025 COVID -19vaccine 6 months (minimum interval 2 months) after second dose​.\n**If previously unvaccinated or receiving initial vaccination series, at least 2 doses of 2024 –2025 vaccine are recommended, and depending on \nvaccination history more may be needed. This additional 2024– 2025 vaccine dose is recommended 6 months (minimum interval 2 months) after \ncompletion of initial vaccination series.​8\nEtR Domain:\nPublic Health Problem \n9\nCOVID -19 circulates year -round.\nReported was last updated on October 16, 2024. \nAll results presented from nucleic acid amplification tests which represent >90% of the diagnostic tests reported to NREVSS. The last three weeks of data may be less complete. NREVSS is an abbreviation for the \nNational Respiratory and Enteric Virus Surveillance System. For more information on NREVSS, please visit www.cdc.gov/surveillance/nrevss . \nSARS -COV-2: Severe acute respiratory syndromic coronavirus type 2\nFlu: Influenza viruses types are combined but reported by type and subtype depending on the testing capabilities of each cont ributing laboratory. \nRSV: Respiratory Syncytial Virus. Types A and B are reported but not shown separately in this report. \nhttps://www.cdc.gov/nrevss/php/dashboard/index.html  \nNational weekly percent positive for SARS -COV -2, RSV and influenza reported to NREVSS, August 27, 2022 through October 12, 2024\n10\nCOVID -19 has consistently peaked in winter and late - \nsummer.\nNational Respiratory and Enteric Virus Surveillance System (NREVSS)11\nCOVID- 19–associated hospitalizations also peaked in \nwinter and late -summer.\nNREVSS: National Respiratory and Enteric Virus Surveillance System12\nFactors that could impact COVID -19 periodicity\nFactor Potential contributors\nHost •Natural infection (reinfection)\n•Timing of vaccination \n•Waning immunity\nVirus •Variant emergence and displacement \n•Variant characteristics (e.g., immune escape,  transmissibility)\nEnvironment •Temperature\n•Relative humidity\n•UV radiation\nBehavior\n  •Travel and mobility\n•Time spent indoors\n•School and daycare schedules\n•Holidays and large gatherings\n13\nPublic Health Problem: older adults\n14\nAdults ages ≥65 years comprise 2/3 of all COVID- 19–\nassociated hospitalizations among adults.\nduring this same period of October 2023 through August 2024, children and adolescents ages 17 years and younger comprised 4% of all COVID -19-associated hospitalizations.0%10%20%30%40%50%60%70%80%90%100%Percent of adults hospitalized with COVID -19\nSurveillance week end datePercent of weekly COVID -19–associated hospitalizations, by age group —\nCOVID -NET, March 2020– August 2024\n18–49 years 50–64 years 65–74 years ≥75 years≥75 years=50%\n≥65 years=70%\n15\nCOVID -19–associated deaths per 100,000 population by age \ngroup, United States, January 1, 2023 – September 30, 2024\nSource: Provisional death data from CDC’s National Center for Health Statistics (NCHS), National Vital Statistics System (NVSS).\nProvisional data are non -final counts of deaths based on reported mortality data in NVSS. Deaths include those with COVID -19, coded as ICD –10 code U07.1, as an \nunderlying or contributing cause of death on the death certificate. Death data are displayed by date of death (event). \nhttps://covid.cdc.gov/covid- data -tracker/#demographicsovertime Accessed October 22, 2024.\n16\nSeroprevalence definition: The percentage of people with antibodies against a virus in their blood is known as seroprevalence . \nMethodology available at https://covid.cdc.gov/covid- data -tracker/#nationwide -blood -donor -seroprevalence- 2022  \nhttps://www.cdc.gov/mmwr/volumes/72/wr/mm7222a3.htm  Weighted U.S. SARS -CoV-2 seroprevalence by vaccine and \ninfection history and age, based on blood donations\n24149\n71520\n687070\n110\n0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%65 years and older50 to 64 years30 to 49 yearsOctober 1st – December 31, 2023\nVaccination-only seroprevalence Infection-only seroprevalence Hybrid immunity Neither past infection nor vaccination\n17\nPool of naïve T cells diminishes with age\nImmunosenescence  refers to  age-associated immune decline that may result in an inefficient immune response to \nnovel antigens and an inability to develop proper immunity against infections and upon vaccination.\nde Candia P, Prattichizzo  F, Garavelli S, Matarese G. T Cells: Warriors of SARS -CoV- 2 Infection. Trends Immunol. 2021 Jan;42(1):18- 30. doi: 10.1016/j.it.2020.11.002. Epub 2020 Nov \n13. PMID: 33277181; PMCID: PMC766435118\nInsufficient pools of naïve T \ncells impacts ability to \ngenerate:\n•Neutralizing antibody responses \n•Cytotoxic T cellsAdaptive immunity includes cellular and humoral \nresponses\nRey, Gertrud.  T Cell Responses to Coronavirus Infection are Complicated. https://www.virology.ws/2020/11/05/t -cell-responses -to-coronavirus -infection -are-complicated/19\nPublic health problem: People with \nmoderate or severe immunocompromise\n20\nAbout 1 in 6 (15.6%) persons hospitalized with COVID -19 \nhave an immunocompromising condition.\nData are limited to hospitalizations where COVID -19 is a likely primary reason for admission.16314 162215\n0%10%20%30%40%50%60%70%80%90%100%\nTotal 0–4 5–17 18–49 50–64 ≥65Percent of persons hospitalized with COV I D -19\nA ge groupImmunocompromising condition among persons with COVID -19–associated hospitalization, by age group —\nCOVID -NET, July 2023 –May 2024\nImmunocompromising condition No immunocompromising condition\n21\nThe most common immunocompromising conditions \namong persons hospitalized with COVID -19 include:\n* Within the 12 months before admission\n** Current/in treatment or diagnosed in the 12 months before admission\n***  Within 2 weeks before admission. Does not include inhaled, intranasal steroids or intramuscular or intra -articular injectio n of steroids.\nData are limited to hospitalizations where COVID -19 is a likely primary reason for admission.46\n34\n26\n22\n9\n6\n5\n4\n3\n2\n1\n0.8\n0.1\n10 5 10 15 20 25 30 35 40 45 50\n* Immunosuppressive therapy\n** Solid organ malignancy\n*** Steroid therapy\n** Metastatic cancer\nSolid organ transplant\n** Lymphoma/Hodgkins/Non-Hodgkins\nHIV infection\n** Leukemia\nBone marrow transplant\nImmunoglobulin deficiency\n** Multiple myeloma\nAIDS or CD4 count <200\nGraft vs. host disease\nOther immunocompromising conditionsPercent of persons hospitalized with C OV I D -19Prevalence of immunocompromising conditions among adults hospitalized with COVID -19 with immunocompromised status — \nCOVID -NET, July 2023– May 2024\nPrevalence of conditions among \nthe 16% of hospitalized persons \nwith immunocompromising \nconditions\n22\nRisk for severe outcomes during COVID -19–associated \nhospitalization among adults varies by immunocompromising \ncondition status. \nData are limited to hospitalizations where COVID -19 is a likely primary reason for admission.27\n18\n15 15\n6\n4\n051015202530\nICU admission Invasive mechanical ventilation In-hospital deathPercent of persons hospitalized with C OV I D -19Prevalence of outcomes and interventions among adults ages ≥18 years hospitalized with COVID -19, \nby immunocompromising condition status —  COVID -NET, July 2023– May 2024\nImmunocompromising condition No immunocompromising conditionSample size with I.C. condition = 512\n23\nDomain Equity Question:\nDoes the problem impact all populations equally? \n24\nAge-adjusted cumulative COVID- 19 hospitalizations per \n100,000 population by race and ethnicity — COVID -NET, \nOctober 2023 – September 2024\nA/PI: Asian or Pacific Islander; AI/AN: American Indian or Alaska Native\nCDC COVID Data Tracker. https://covid.cdc.gov/covid -data -tracker/#covidnet -hospitalization -network . Accessed October 15, 2024Equity\n 25\nNumber of chronic conditions by age among Asian, \nBlack, Latino/Hispanic, and White adults in the National \nHealth Interview Survey, 1999 to 2018 \nCaraballo C, Herrin J, Mahajan S, et al. Temporal Trends in Racial and Ethnic Disparities in Multimorbidity Prevalence in the  United States, 1999 -2018. Am J Med . 2022;135(9):1083-\n1092.e14. doi:10.1016/j.amjmed.2022.04.010 Equity 26\nDifference in prevalence of multiple chronic conditions \nby age and race/ethnicity, National Health Interview \nSurvey, 1999 to 2018\nCaraballo C, Herrin J, Mahajan S, et al. Temporal Trends in Racial and Ethnic Disparities in Multimorbidity Prevalence in the  United States, 1999 -2018. Am J Med . \n2022;135(9):1083- 1092.e14. doi:10.1016/j.amjmed.2022.04.010Equity 27\nPrevalence of Self- Reported Status of \nImmunosuppression Among US Adults, NHIS 2021\n7\n576\n48\n4\n02468101214161820\nOverall Hispanic White, non-\nHispanicBlack, non-\nHispanicAsian, non-\nHispanicAI/AN, non-\nHispanicOther, non-\nHispanicWeighted Prevalence by Race and Ethnicity, per 100 US population\n95% Confidence interval represented by error bars\nOther: NHIS includes a choice for “some other race” in the questionnaire for respondents who do not identify with the racial and ethnic categories provided \nhttps://jamanetwork.com/journals/jama/fullarticle/2815274  Equity 28\nPrevalence of Self- Reported Status of \nImmunosuppression Among US Adults, NHIS 2021\n58\n02468101214161820\nMale FemaleWeighted Prevalence by Sex, per 100 \nUS population\n95% Confidence interval represented by error bars\nhttps://jamanetwork.com/journals/jama/fullarticle/2815274  7\n3\n02468101214161820\nInsured UninsuredWeighted Prevalence by Health \nInsurance Status, per 100 US population\nEquity 29\n•SARS -CoV-2 continues to circulate year- round with peaks occurring in the winter and late \nsummer\n•Adults ≥65 years have the highest rates of hospitalizations due to COVID -19 compared to other \nage groups, though hospitalizations have decreased over time\n•Adults ≥65 years also have the highest rates of death due to COVID -19\n•Adults ≥65 years have higher rates of vaccination -only seroprevalence compared to younger ages\n•Age-adjusted COVID -19 associated hospitalizations are highest among American Indian/Alaska \nNative non -Hispanic persons followed by Black non -Hispanic persons and are lowest among Asian \nand Pacific Islander non -Hispanic persons\n•The number of chronic conditions increases with increasing age, and are higher among Black non -\nHispanic persons than other racial and ethnic groups  \n-By age 50, approximately 25% of Black non -Hispanic persons have 2 or more chronic conditions, and by \nage 65, approximately 50% have 2 or more chronic conditionsSummary\nPublic Health Problem –  Adults ages ≥65 years\n30\n•About 1 in 6 people hospitalized with COVID- 19 have an immunocompromising \ncondition \n•Risk for severe outcomes during COVID -19–associated hospitalization among adults \nvaries by immunocompromising condition status. \n•Prevalence of self -reported immunosuppression status differs by race and ethnicity, \nsex, and health insurance statusSummary\nPublic Health Problem –  People with moderate or \nsevere immunocompromise\n31\nPublic Health Problem\nWork Group Interpretation\nIs COVID -19 disease among adults ages ≥65 years of public health \nimportance?\noNo oProbably no oProbably yes oYes oVaries oDon’t know\nIs COVID -19 disease among persons with moderate or severe \nimmunocompromise of public health importance?\noNo oProbably no oProbably yes oYes oVaries oDon’t know\n32\nEtR Domain:\nBenefits and Harms \n33\nCOVID -19 vaccine effectiveness (VE) against hospitalization  wanes over time, \nbut is more sustained against critical illness , though some waning is evident\nData from VISION and IVY showing VE by vaccine formulation of most recent dose.\n-20020406080100\n7-59 or 14-59 60-119 120-179 180-239* 240-299* 300-364* 365+Vaccine effectiveness (%)\nDays since last dose\nRecipients of bivalent and 2023 –2024 doses included in this analysis received a single dose of the most recent formulation.\nSources: DeCuir, et al., MMWR 2023/  Lin k-Gelles, ACIP Slides, April 20, 2022 ; CDC unpublished data updated from Link -Gelles, ACIP Slides, June 23, 2023; CDC unpublished data updated from: Link -Gelles, ACIP Slides, June 27, 2024\n* For original monovalent doses, VE for hospitalization was for 180 -364 days from last dose combined. For 2023– 2024 doses, VE fo r hospitalization was for ≥180 days combined, with a median of 228 days (IQR: 202- 259).Hosp italization Critical illness\nOriginal monovalent (adults aged 50+; ref: unvaccinated)\nBivalent (adults aged 18+; ref: unvaccinated)  \n2023– 2024 (adults aged 18+; ref: no 2023– 2024 dose)  Benefits\n34\nMicrosimulation modeling study compares frequency \nof COVID- 19 vaccination by risk group\nPark, H.J., Gonsalves, G.S., Tan, S.T. et al. Comparing frequency of booster vaccination to prevent \nsevere COVID -19 by risk group in the United States. Nat Commun 15, 1883 (2024). \nhttps://doi.org/10.1038/s41467- 024- 45549- 9 Step 1 : Assign to risk group\n•Age group: 18-49, 50- 64, 65- 74, 75+ years\n•Immune status: immunocompetent, \nimmunocompromised (mild, moderate/severe)Step 3 : Calibrate model to data\n•Epidemiologic data: COVID -19 severe incidence, seroprevalence\n•Calibrated to ~September 2022\nComputer \nsimulation\nStep 2 : Simulate vaccine -induced or hybrid protection\n•Vaccine: number doses, timing of last dose\n•Prior infection: yes/no, timing of last infection\n•Vaccine/hybrid protection data: level of protection and waning curves Step 4 : Run simulation of different vaccine strategies\n•Vaccine strategies: One -time (1 dose); Annual (2 doses), Semi -annual (4 \ndoses); Simulate over 2 -years\n•Simulate person- level waning of protection and COVID -19 at each time step \n(static infection model)\n•Primary study outcome: Absolute annual risk of severe COVID -19\n3 Month \n06 1\nBenefits35\nAnnual and semiannual COVID -19 vaccine doses likely to have largest benefit in \npeople ages ≥65 years and people who are immunocompromised\nAbsolute annual risk of \nCOVID -19 hospitalization* \n(cases per 100,000; \nuncertainty interval)Annual risk reduction of COVID -19 \nhospitalization* NNT to avert one \nCOVID -19 \nhospitalization* Absolute risk (cases \nper 100,000)Relative risk \n(%)\nOne -time booster\n18-49 years 98 (85 - 125) -- -- --\n50-64 years 199 (185 - 238) -- -- --\n65-74 years 524 (499 -  562) -- -- --\n75+ years 1,398 (1,332 - 1,501) -- -- --\nImmunocompromised (mild) 1,290 (1,205 –  1,403) -- -- --\nImmunocompromised (moderate/severe) 1,367 (1,266- 1,503) -- -- --\nAnnual booster\n18-49 years 84 (74 - 106) 14 14% 3,534\n50-64 years 171 (159 -  202) 28 14% 1,806\n65-74 years 446 (425 -  475) 78 15% 642\n75+ years 1,198 (1,144 - 1,272) 199 14% 251\nImmunocompromised (mild) 1,180 (1,088 - 1,316) 110 9% 456\nImmunocompromised (moderate/severe) 1,183 (1,091- 1,307) 184 13% 273\nSemiannual booster (every 6 months)\n18-49 years 72 (64 - 90) 26 27% 1,916\n50-64 years 147 (136 -  171) 52 26% 968\n65-74 years 382 (365- 404) 142 27% 353\n75+ years 1,030 (988 - 1,088) 368 26% 136\nImmunocompromised (mild) 1,095 (987 - 1,255) 195 15% 257\nImmunocompromised (moderate/severe) 1,057 (966- 1,183) 310 23% 162\nNNT: number of persons needed to follow vaccine strategy to prevent one severe COVID -19 case over 2- year \nperiod\n*Hospitalization for COVID -19 defined as severe COVID -19 in publication \nNote: incidence of severe COVID -19 is currently lower than when this model was calibrated, so measures of \nabsolute risk are likely an overestimate and NNTs are likely an underestimate based on current epidemiologyPark, H.J., Gonsalves, G.S., Tan, S.T. et al. Comparing frequency of booster \nvaccination to prevent severe COVID -19 by risk group in the United States. Nat \nCommun 15, 1883 (2024). https://doi.org/10.1038/s41467- 024- 45549- 9 Benefits36\n•2023– 2024 COVID -19 vaccination provided increased protection against COVID -19 associated \nED/UC visits and hospitalizations compared to no 2023 –2024 vaccine dose.\n-Protection waned to 0 against COVID -19-associated ED/UC visits and hospitalization by ~4 -6 months\n•Waning patterns of 2023 –2024 COVID -19 vaccines appeared similar to previous COVID -19 vaccine \nformulations; most durable protections appeared to be for critical illness\n-VE against critical illness remained above 40% at 5 months after vaccination among those ≥65 years\n•As with previous COVID -19 vaccine formulations, effectiveness was similar across age groups\n•Data from prior seasons shows that an additional dose appeared to provide some additional \nprotection\n•Updated COVID -19 vaccination helped provide protection against COVID -19–related \nthromboembolic events (ischemic stroke, venous thromboembolism, and myocardial infarction) in adults 65 years and older.\n•Based on modeling data, annual and semiannual COVID -19 vaccine doses likely to have largest \nbenefit in people ages ≥65 years and people who are immunocompromisedSummary of Benefits: Adults ≥65 years\nBenefitsED/UC: Emergency Department/Urgent Care 37\n•COVID -19 vaccines provided protection for both persons with and without immunocompromise.\n•Patterns of COVID -19 VE in immunocompromised were different season -to-season, with generally \nlower VE compared to non -immunocompromised, but with inconsistent waning patterns\n-During 2023– 2024, VE against hospitalization in people with immunocompromising conditions waned to 0 by \n~4-6 months.\n•This inconsistency in waning patterns is likely multifactorial, including:\n-Heterogeneity among those classified as immunocompromised\n-Variation in underlying immunity and response to prior infection\n-Differing health behaviors (e.g., masking, social distancing) over time and by immunocompromise status\n•Based on modeling data, annual and semiannual COVID -19 vaccine doses likely to have largest \nbenefit in people ages ≥65 years and people who are immunocompromisedSummary of Benefits: People with moderate or severe \nimmunocompromise\nBenefits38\nReactogenicity and health impacts of COVID -19 vaccine were \nreported less frequently in those ≥65 years vs younger age \ngroups\nPresented to ACIP on Feb 24, 2023\n HarmsV-safe:  reactions and health impacts reported by participants aged ≥5 years at \nleast once in days 0 -7 after bivalent booster dose, by age group, 2022 –2023\n39\nAmong persons aged ≥50 years, injection site and systemic \nreactions were reported less frequently to v -safe in subsequent \ndosing following the initial vaccination series\nhttps://www.cdc.gov/mmwr/volumes/71/wr/mm7130a4.htm?s_cid=mm7130a4_w\n HarmsV-safe:  reactions and health impacts reported by participants aged ≥50 years at \nleast once in days 0 -7 after doses 1 – 4, through July 2022\n40\nLocal and systemic reactions were less frequently reported to \nv-safe after mRNA booster (dose 4) than after the 3- dose initial \nseries\nhttps://www.cdc.gov/mmwr/volumes/71/wr/mm7128a3.htm?s_cid=mm7128a3_w\n HarmsV-safe: reactions and health impacts reported by participants aged ≥12 years \nwith  presumed immunocompromise status  at least once in days 0 -7 after \ndoses 1 –4, through March 2022\n41\nVSD signal for ischemic stroke in 2022 –2023\n•Vaccine Safety Datalink (VSD) Rapid Cycle Analysis (RCA) is weekly sequential active \nsurveillance\n•Ischemic stroke was a prespecified outcome monitored by RCA\n-No signal following primary series doses (2020– 2021)\n-No signal following first booster (3rd) dose (2021– 2022)\n-Signal following first bivalent vaccine dose (2022– 2023)\n•For Pfizer -BioNTech COVID- 19 vaccine, bivalent among people aged ≥65 years in the 1– 21 \ndays risk interval following vaccination compared to days 22– 42\n•Presented to ACIP on February 24, 2023\n•Follow -up ACIP presentations in April 2023 and October 2023\n–Reviewed findings from 7 studies done in 4 countries\n–No clear and consistent evidence of a safety problem\nhttps://www.fda.gov/vaccines -blood -biologics/safety -availability -biologics/cdc -and- fda-identify -preliminary -covid -19-vaccine -safety-signal -persons -aged -65-years -and- older Harms42\nIt is currently unclear if the VSD signal for ischemic stroke in \n2023– 2024 represents a true increased risk following COVID -19 \nvaccination\n•Vaccine Safety Datalink (VSD) Rapid Cycle Analysis (RCA) for 2023– 2024 identified \nstatistical signals for ischemic stroke following:\n-Moderna (aged ≥65 years) \n-Pfizer (aged 50 -64 years) \n•Presented to ACIP on June 27, 2024\n•CDC and FDA are continuing to evaluate this outcome\nhttps://www.cdc.gov/acip/meetings/presentation- slides -june -26-28-2024.html  Harms43\n•VSD had not identified any signals for GBS with previous mRNA COVID- 19 vaccine formulations (i.e., \noriginal primary series, original booster, or 2022– 2023 bivalent) \n•The increased rate ratio observed for Pfizer COVID -19 vaccine during the 2023 –2024 season may or \nmay not represent a true risk\n-A large  number of analyses may find some associations by chance alone\n-Surveillance  analyses may have residual confounding\n•If there is a true risk, then t he estimated excess GBS cases of 4.1 per million doses is similar to \nprevious estimates for other vaccines for adults\n-Influenza:  1 -  2 cases per million doses1\n-Recombinant Zoster Vaccine:  3 - 6 cases per million doses2\n•There were insufficient doses of Moderna or Novavax vaccines administered in the VSD to assess \nthe rate of GBS with those vaccinesVSD signal for Guillain -Barré syndrome (GBS) in 2023–\n2024\n1 Perez -Vilar  S, et al. Guillain- Barré Syndrome After High -Dose Influenza Vaccine Administration in the United States, 2018 -2019 Season . J Infect Dis. 2021 Feb 13;223(3):416 -425.\n2 Janusz CB, et al. Projected risks and health benefits of vaccination against herpes zoster and related complications in US adults . Human Vaccines & Immunotherapeutics , 18(5), 2022. Harms44\nPending information relevant to VSD signals for \nischemic stroke and GBS\n•FDA’s 2023 –2024 COVID-19 vaccine safety surveillance using commercial \nhealth plans and Medicare claims databases results are expected later this \nyear, which will provide additional information about ischemic stroke, GBS, and other outcomes\n•A follow -up VSD study is in progress to further examine the risk of ischemic \nstroke after mRNA COVID-19 vaccines during 2022 –2023 and 2023 –2024\nVSD: Vaccine Safety Datalink; GBS: Guillain- Barré syndrome Harms45\nSummary: COVID -19 vaccine safety\n•Robust safety surveillance over 3 years of COVID -19 vaccine use demonstrated that \nserious adverse events have been rare.\n-Anaphylactic reactions have been rarely reported following receipt of COVID- 19 vaccines.\n-Rare risk of myocarditis and pericarditis, however this is predominately in males ages 12- 39 years. \n•There has been no increased risk observed in adults aged ≥65 years\n•Whether the risk might be different in immunocompromised people is unknown\n•COVID -19 vaccine doses continue to be reactogenic\n-The rate of local and systemic reactions reported to V -safe was lower with additional doses than \nafter the initial series\n-Most vaccine recipients have mild reactions, but during 2023– 2024, at least 10% reported health \nimpact events during the 7 days post -vaccination, such as being unable to complete daily activities\n-Overall, symptoms less frequent and severe among older adults compared with adolescents and \nyounger adults.\nHarms46\nDomain Equity Question:\nAre the desirable and undesirable anticipated effects demonstrated across \nall populations equally? \n47\nAre the desirable and undesirable anticipated effects \ndemonstrated across all populations equally? \n•There is no evidence to suggest that COVID- 19 vaccine effectiveness varies \nsubstantially by race/ethnicity.1,2\n-Differences in vaccine hesitancy/uptake, crowding, access to care, and prior infection could \nimpact vaccine effectiveness and these factors may also differ by race/ethnicity. \n•There is no evidence to suggest that COVID- 19 vaccine safety profiles vary by \nrace/ethnicity, however risk has been shown to differ by age and sex.\n-Risk for myocarditis is highest in adolescent and young adult males.\n•Benefits and harms for the U.S. population are best assessed when clinical trial and \nstudy populations are optimally representative of the U.S. population.\n1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9619452/   \n2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9763212/  Equity 48\nBenefits and Harms \nHow substantial are the desirable anticipated effects of a second dose of \n2024 –2025 COVID -19 vaccine in adults ages ≥65 years?\n• How substantial are the anticipated effects for each main outcome for \nwhich there is a desirable effect?\noMinimal oSmall oModerate oLarge oVaries oDon’t know\n49\nBenefits and Harms \nHow substantial are the undesirable anticipated effects of a second dose of \n2024 –2025 COVID -19 vaccine in adults ages ≥65 years?\n• How substantial are the anticipated effects for each main outcome for \nwhich there is an undesirable effect?\noMinimal oSmall oModerate oLarge oVaries oDon’t know\nMajority Opinion Minority Opinion 50\nBenefits and Harms \nDo the desirable effects of a second dose of 2024 –2025 COVID -19 vaccine \noutweigh the undesirable effects in adults ages ≥65 years?\n• What is the balance between the desirable effects relative to the \nundesirable effects?\noFavors intervention (Additional dose of 2024 – 2025 COVID -19 vaccine)\noFavors comparison (No additional dose of 2024 – 2025 COVID -19 vaccine)\noFavors both\noFavors neither\noUnclear\n51\nBenefits and Harms \nHow substantial are the desirable anticipated effects of a second dose of \n2024 –2025 COVID -19 vaccine in people with moderate or severe \nimmunocompromise?\n• How substantial are the anticipated effects for each main outcome for which there is a desirable effect?\noMinimal oSmall oModerate oLarge oVaries oDon’t know\n52\nBenefits and Harms \nHow substantial are the undesirable anticipated effects of a second dose of \n2024 –2025 COVID -19 vaccine in  people with moderate or severe \nimmunocompromise?\n• How substantial are the anticipated effects for each main outcome for which there is an undesirable effect?\noMinimal oSmall oModerate oLarge oVaries oDon’t know\nMajority Opinion Minority Opinion 53\nBenefits and Harms \nDo the desirable effects of a second dose of 2024 –2025 COVID -19 vaccine \noutweigh the undesirable effects in people with moderate or severe \nimmunocompromise?\n• What is the balance between the desirable effects relative to the \nundesirable effects?\noFavors intervention (second dose of 2024 – 2025 COVID -19 vaccine)\noFavors comparison (no second dose of 2024 – 2025 COVID -19 vaccine)\noFavors both\noFavors neither\noUnclear\n54\nBenefits and Harms \nHow substantial are the desirable anticipated effects of additional doses (i.e., \n3 or more) of 2024 –2025 COVID -19 vaccine in people with moderate or \nsevere immunocompromise?\n• How substantial are the anticipated effects for each main outcome for which there is a desirable effect?\noMinimal oSmall oModerate oLarge oVaries oDon’t know\n55\nBenefits and Harms \nHow substantial are the undesirable anticipated effects of additional doses \n(i.e., 3 or more) of 2024 –2025 COVID -19 vaccine in people with moderate or \nsevere immunocompromise?\n• How substantial are the anticipated effects for each main outcome for which there is an undesirable effect?\noMinimal oSmall oModerate oLarge oVaries oDon’t know\n56\nBenefits and Harms \nDo the desirable effects of additional doses (i.e., 3 or more) of 2024 –2025 \nCOVID -19 vaccine outweigh the undesirable effects in people with moderate \nor severe immunocompromise?\n• What is the balance between the desirable effects relative to the \nundesirable effects?\noFavors intervention (Additional doses of 2024 – 2025 COVID -19 vaccine)\noFavors comparison (No additional dose of 2024 – 2025 COVID -19 vaccine)\noFavors both\noFavors neither\noUnclear\n57\nEtR Domain:\nValues  \n58\nKey attitudes and experiences among adults 18 years and older, \nJuly 2024\nNational Immunization Survey -Adult COVID Module (NIS -ACM)\n21%49%63%\n31%50%63%\n38%64%74%\n0%10%20%30%40%50%60%70%80%90%100%\nConcerned about COVID-19\ndiseaseConfidence in COVID-19 vaccine\nsafetyConfidence that COVID-19 vaccine\nis somewhat or very important to\nprotect mePercentCOVID -19 Vaccination Key Attitudes and Experiences by Age \nGroup Among Adults Age ≥18 Years, NIS -ACM, July 2024\n18-49 years 50-64 years 65+ years\nThe July estimates are based on data collected July 1 –27 2024.\nCDC. COVID -19 Vaccination Coverage and Vaccine Confidence Among Adults. \nhttps://www.cdc.gov/covidvaxview/interactive/adults.html?CDC_AAref_Val=https://www.cdc.gov/vaccines/imz -managers/coverage/covidv axview/interactive/adults.html  \nAccessed October 3, 2024Generally, adults ages 65 years \nand older were more concerned about COVID -19 \ndisease and had higher confidence in vaccine safety and vaccine importance; those ages 18 –49 years and 50– 64 \nyears were less concerned and confident.\n59\n•Limited data exists on concern about COVID -19 disease specifically in \npeople with moderate or severe immunocompromiseValues: People with moderate or severe \nimmunocompromise\n60\n24.7\n32.6\n25.915.2\n19.2\n19.915.8\n16.4\n20.013.0\n10.9\n8.731.3\n20.9\n25.5\n0 25 50 75 100Three or more dose s\n(≥18 years with health \ncondition,† N=459)Second dose ( ≥65 years &\n≥18 years with health\ncondition,† N=1,263)First dose ( ≥18 years,\nN=4,044)\nWeighted %Definitely will Probably will Unsure Probably will not Definitely will not\n*165 respondents excluded from analysis due to inconsistent answers. \n† Health condition includes cancer (excluding basal cell carcinoma and squamous cell carcinoma), solid organ or blood stem cell  transplant, HIV, and immunocompromised state. Intent to receive 2024– 2025 COVID -19 vaccination among \nadults ≥18 years\nOmnibus Surveys, August 8 –26, 2024 (N=4,044)*\n61\nDomain Equity Question:\nIs there important variability in how patients or populations value the \noutcome?  \n62\nKey attitudes and experiences among adults 65 years and older, \nJuly 2024\nNational Immunization Survey -Adult COVID Module (NIS -ACM)\n36%67%76%\n37%64%72%\n45%63%88%\n29%51%66%\n0%10%20%30%40%50%60%70%80%90%100%\nConcerned about COVID-19 disease Confidence in COVID-19 vaccine safety Confidence that COVID-19 vaccine is\nsomewhat or very important to protect mePercentCOVID -19 Vaccination Key Attitudes and Experiences by Race & Ethnicity \nAmong Adults Age 65 Years and Older, NIS -ACM, July 2024\nHispanic White, non-Hispanic Black, non-Hispanic Other or multiple races, non-Hispanic\nThe July estimates are based on data collected July 1 –27 2024.\nCDC. COVID -19 Vaccination Coverage and Vaccine Confidence Among Adults. \nhttps://www.cdc.gov/covidvaxview/interactive/adults.html?CDC_AAref_Val=https://www.cdc.gov/vaccines/imz -managers/coverage/covidv axview/interactive/adults.html    \nAccessed October 3, 2024Equity 63\nValues \nCriteria 1:\nDo adults ages ≥65 years feel that the desirable effects are large relative to \nundesirable effects?\n• How do adults ages ≥65 years view the balance of desirable versus \nundesirable effects?\n• Would adults ages ≥65 years feel that the benefits outweigh the harms?\noMinimal oSmall oModerate oLarge oVaries oDon’t know\n64\nValues \nCriteria 2:\nIs there important uncertainty about, or variability in, how adults ages ≥65 \nyears  value the main outcomes?\n• Is there evidence that the variability is large enough to lead to different \ndecisions?\noImportant uncertainty or variability\noProbably important uncertainty or variability\noProbably not important uncertainty or variability\noNo important uncertainty or variability\noNo known undesirable outcomes\n65\nValues \nCriteria 1:\nDo people with moderate or severe immunocompromise feel that the \ndesirable effects are large relative to undesirable effects?\n• How do immunocompromised persons ≥6 months of age view the balance \nof desirable versus undesirable effects?\n• Would immunocompromised persons ≥6 months of age feel that the \nbenefits outweigh the harms?\noMinimal oSmall oModerate oLarge oVaries oDon’t know\n66\nValues \nCriteria 2:\nIs there important uncertainty about, or variability in, how persons with \nmoderate or severe immunocompromise value the main outcomes?\n• Is there evidence that the variability is large enough to lead to different \ndecisions?\noImportant uncertainty or variability\noProbably important uncertainty or variability\noProbably not important uncertainty or variability\noNo important uncertainty or variability\noNo known undesirable outcomes\n67\nEtR Domain:\nAcceptability  \n68\nPercent vaccinated with 2023– 2024 COVID -19 vaccine \nNational Immunization Survey -Adult COVID Module (NIS -ACM)\nhttps://www.cdc.gov/covidvaxview/weekly -dashboard/adult -vaccination -coverage.html   accessed October 4, 2024\n69\nCOVID -19 vaccination coverage (≥1 dose and ≥2 doses) among \nadults 65 years and older, 2023– 2024\nNational Immunization Survey -Adult COVID Module (NIS -ACM)\n3.85.77.38.9\n0.020.040.060.080.0\n9/30/2023\n10/7/2023\n10/14/2023\n10/21/2023\n10/28/2023\n11/4/2023\n11/11/2023\n11/18/2023\n11/25/2023\n12/2/202312/9/2023\n12/16/2023\n12/23/2023\n12/30/2023\n1/6/2024\n1/13/2024\n1/20/2024\n1/27/2024\n2/3/2024\n2/10/2024\n2/17/2024\n2/24/2024\n3/2/20243/9/2024\n3/16/20243/23/2024\n3/30/2024\n4/6/2024\n4/13/2024\n4/20/2024\n4/27/2024\n5/4/2024\n5/11/20245/18/2024\n5/25/2024\n6/1/2024\n6/8/2024\n6/15/20246/22/2024\n6/29/2024Vaccination coverage (%)\nWeek ending date≥1 dose (65+)\n≥2 doses (65+)\n39.3\n70\nCOVID -19 Vaccination Coverage (≥2 Doses) Among Adults 65 Years \nand Older and Adults 18 Years and Older Who Are \nImmunocompromised, 2024\nNational Immunization Survey -Adult COVID Module (NIS -ACM)\n3.85.77.38.9\n2.5 3.34.5 5.4\n0.010.020.030.040.0\nMar-24 Apr-24 May-24 Jun-24Vaccination coverage (%)\nData collection month≥2 doses (65+)\n≥2 doses (18+ immunocompromised)\n71\nA healthcare provider \nrecommendation for COVID -19 \nvaccine was highest among adults ages ≥65 yearsHealthcare provider recommendation for COVID -19 vaccine, by \nage, among adults ages 18 years and older, July 2024 \nNational Immunization Survey -Adult COVID Module (NIS -ACM)\n22%\n18%25%28%\n0%5%10%15%20%25%30%35%Healthcare Provider Recommendation for COVID -19 Vaccine \nby Age Among Adults Ages 18 years and older, \nNIS-ACM, July 2024\nOverall 18-49 years 50-64 years ≥65 years\nThe July estimates are based on data collected July 1 –27 2024.\nCDC. COVID -19 Vaccination Coverage and Vaccine Confidence Among Adults. \nhttps://www.cdc.gov/covidvaxview/interactive/adults.html?CDC_AAref_Val=https://www.cdc.gov/vaccines/imz -managers/coverage/covidv axview/interactive/adults.html   \nAccessed October 4, 202472\nA healthcare provider recommendation was higher among adults 65 and older \nwho had received ≥2 doses of 2023 –2024 COVID -19 vaccine by end of June 2024\nNational Immunization Survey -Adult COVID Module (NIS -ACM)\nSVI: Social vulnerability index  \n*Statistically significant at p<0.05 (referent categories: No health condition, No provider recommendation).7.213.68.79.713.97.710.38.69.38.7\n0.0 10.0 20.0 30.0 40.0 50.0 60.0No provider recommendationHealth care provider recommended COVID-19 vaccineDoes not have any disabilityHas a disabilityImmunocompromisedNo health conditionHas health conditionHigh SVIModerate SVILow SVI\nW eighted % (95% C I )*\n*\n73\n70% of healthcare provider respondents reported recommending a second \nCOVID -19 vaccination to eligible patients aged 65 years and older most of the \ntime or always, October 2024 Survey\nN= 1,000, data from University of Iowa/RAND, unpublished survey of physicians, advanced practice providers, pharmacists, and nur ses who spend at least 50% of time providing \noutpatient care and have vaccines administered at worksite. October 9 -16 2024. 74\n68% of healthcare provider respondents reported recommending a \nsecond COVID -19 vaccination to eligible patients who were \nimmunocompromised most of the time or always  , October 2024 Survey\nN= 1,000,  data from University of Iowa/RAND, unpublished survey of physicians, advanced practice providers, pharmacists, and nurses who spend at least 50% of time providing \noutpatient care and have vaccines administered at worksite. October 9 -16 2024. 75\n•Feedback was obtained via the WG liaisons from organizations* that focus on older \nadults, people with immunocompromise, healthcare providers, and pharmacists\n•Prefer age-based recommendations  (universal) over risk -based or shared clinical \ndecision -making \n-Implementation challenges for both risk -based and shared clinical decision -making on top of an \nalready complicated vaccination schedule\n-Shared clinical decision -making recommendations can appear to have lower confidence and are \ndifficult to communicate\n•Frequent changes in vaccine recommendations create confusion\n•Most preferred one to two total doses a year \n•Reiterate that  self-attestation of being moderately or severely immunocompromised \nis permissibleWork Group Professional Organization Liaison Feedback\n*Infectious Diseases Society of America, American Geriatrics Society, American Pharmacists Association, Society for Healthcar e Epidemiology of America 76\nDomain Equity Question:\nIs the intervention equally acceptable across all populations? \n77\n2023– 2024 COVID -19vaccine ≥2 dose coverage among adults aged ≥65 years varied by race \nand ethnicity and urbanicity\nNational Immunization Survey- Adult COVID Module (NIS -ACM)\n21.813.516.29.011.18.112.76.78.311.17.49.09.210.69.18.78.9\n0.0 10.0 20.0 30.0 40.0 50.0 60.0AI/ANOther/multiple, non-HispanicNH/OPIHispanicBlack, non-HispanicWhite, non-HispanicAsianRuralSuburbanUrban65-6970-7475-7980+MaleFemaleOverall 65+\nW eighted % (95% C I )9.48.48.510.510.78.818.011.17.87.76.88.97.39.38.08.4\n0.0 10.0 20.0 30.0 40.0 50.0 60.0Income unknownAbove poverty, >=$75KAbove poverty, <$75KBelow povertyUninsuredInsuredHHS Region 10HHS Region 9HHS Region 8HHS Region 7HHS Region 6HHS Region 5HHS Region 4HHS Region 3HHS Region 2HHS Region 1\nW eighted % (95% C I )*\n**\nAI/AN: American Indian or Alaska Native; NH/OPI: Native Hawaiian or Other Pacific Islander.\n*Statistically significant at p<0.05 (referent categories: Age 65 -69, Rural, White non -Hispanic, HHS Region 1).*\nHHS  R egions     7: IA,K S,MO,NE\n1: CT,ME,MA,NH,RI,VT  4: AL,FL,GA,K Y ,MS,NC,SC,TN  8: CO,MT,ND,SD,UT,WY\n2: NJ,NY ,PR,VI   5: IL,IN,MI,MN,OH,WI  9: AZ,CA,HI,NV,GU\n3: DE,DC,MD,PA,VA,WV  6: AR,LA,NM,OK ,TX  10: AK ,ID,OR,WAEquity 78\n4.04.76.56.11.85.64.96.35.05.66.25.32.56.55.05.25.45.14.63.89.0\n0.0 10.0 20.0 30.0 40.0 50.0 60.0Income unknownAbove poverty, >=$75KAbove poverty, <$75KBelow povertyUninsuredInsuredHigh SVIModerate SVILow SVIHHS Region 10HHS Region 9HHS Region 8HHS Region 7HHS Region 6HHS Region 5HHS Region 4HHS Region 3HHS Region 2HHS Region 1No provider recommendationHealth care provider recommended\nW eighted % (95% C I )5.13.54.75.91.53.05.95.53.03.713.58.24.65.4\n0.0 10.0 20.0 30.0 40.0 50.0 60.0AI/ANOther/multiple, non-HispanicNH/OPIHispanicBlack, non-HispanicWhite, non-HispanicAsianRuralSuburbanUrban18-4950-6465+MaleFemaleOverall 18+ Immunocompromised\nW eighted % (95% C I )2023– 2024 COVID -19≥2 dose vaccine coverage among immunocompromised adults ≥18 \nyears varied by urbanicity, race and ethnicity, healthcare provider recommendation and \ninsurance status\nNational Immunization Survey- Adult COVID Module (NIS -ACM)\n*\n**\nNA: estimate not reported because denominator is <30; AI/AN: American Indian or Alaska Native; NH/OPI: Native \nHawaiian or Other Pacific Islander.\n*Statistically significant at p<0.05 (referent categories: Age 18 -49, Rural, White non -Hispanic, No Provider \nRecommendation, Insured).NANA**\nHHS  R egions     7: IA,K S,MO,NE\n1: CT,ME,MA,NH,RI,VT  4: AL,FL,GA,K Y ,MS,NC,SC,TN  8: CO,MT,ND,SD,UT,WY\n2: NJ,NY ,PR,VI   5: IL,IN,MI,MN,OH,WI  9: AZ,CA,HI,NV,GU\n3: DE,DC,MD,PA,VA,WV  6: AR,LA,NM,OK ,TX  10: AK ,ID,OR,WA Equity79\nAcceptability \nWould recommending a second dose of the 2024 – 2025 COVID -19 vaccine for \nadults ages ≥65 years be acceptable to key stakeholders?\n• Are there key stakeholders that would not accept the distribution of \nbenefits and harms?\n• Are there key stakeholders that would not accept the undesirable effects in the short term for the desirable effects (benefits) in the future?\noNo oProbably no oProbably yes oYes oVaries oDon’t know\n80\nAcceptability \nWould recommending a second dose of the 2024 – 2025 COVID -19 vaccine for \npeople ages ≥6 months with moderate or severe immunocompromise be \nacceptable to key stakeholders?\n• Are there key stakeholders that would not accept the distribution of \nbenefits and harms?\n• Are there key stakeholders that would not accept the undesirable effects \nin the short term for the desirable effects (benefits) in the future?\noNo oProbably no oProbably yes oYes oVaries oDon’t know\n81\nAcceptability \nWould recommending additional doses (i.e., 3 or more) of the 2024 – 2025 \nCOVID -19 vaccine for people ages ≥6 months with moderate or severe \nimmunocompromise be acceptable to key stakeholders?\n• Are there key stakeholders that would not accept the distribution of \nbenefits and harms?\n• Are there key stakeholders that would not accept the undesirable effects \nin the short term for the desirable effects (benefits) in the future?\noNo oProbably no oProbably yes oYes oVaries oDon’t know\n83\nEtR Domain:\nFeasibility \n83\nBased on survey data, physicians think shared clinical decision -making \n(SCDM) increases time and confusion1\n1 Kempe A, Lindley MC, O'Leary ST, et al. Shared Clinical Decision- Making Recommendations for Adult Immunization: What Do Physic ians Think? J Gen Intern \nMed . 2021;36(8):2283- 2291. https://pubmed.ncbi.nlm.nih.gov/33528783/ . Numbers cited based on General Internal Medicine physician responses, N=281. \n68% strongly agreed \nSCDM will require more \ntime with patients \n44% either strongly or \nsomewhat agreed they find \nit hard to explain what a \nSCDM recommendation \nmeans to patients \n76% either strongly or \nsomewhat agreed SCDM \ncreates confusion\n42% either strongly or \nsomewhat agreed they did \nnot know how to \nimplement SCDM as \nintended by the ACIP\n84\nDomain Equity Question:\nIs the intervention equally feasible to implement across all populations?\n85\n•Social Determinants of Health drive differences in vaccine access creating \ndisparities in uptake. \n•Additional dose recommendations may further increase these disparities. \nFor example:\n-Insurance: decreased access with the end of the Bridge Access Program\n-Disability: increased prevalence with age creating potential challenges getting to \nvaccination sites\n-Setting: decreased access in setting with existing challenges (e.g., long -term care)\n•In the absence of an ACIP recommendation, decreased access if required to \npay out -of-pocket.Vaccine equity considerations\nEquity 86\nFeasibility \nIs a second dose of the 2024 – 2025 COVID -19 vaccine feasible to implement \namong adults ≥65 years ?\n• Is a second dose of the 2024 – 2025 COVID -19 vaccine program \nsustainable?\n• Are there barriers that are likely to limit the feasibility of implementing a \nsecond dose of the 2024 – 2025  COVID -19 vaccine or require \nconsiderations when implementing it?\n• Is access to a second dose of the 2024 – 2025 COVID -19 vaccine an \nimportant concern?\noNo oProbably no oProbably yes oYes oVaries oDon’t know\nMajority Opinion Minority Opinion 87\nFeasibility \nIs a second dose of the 2024 – 2025 COVID -19 vaccine feasible to implement \namong persons with moderate or severe immunocompromise ?\n• Is a second dose of the 2024 – 2025 COVID -19 vaccine program \nsustainable?\n• Are there barriers that are likely to limit the feasibility of implementing a \nsecond dose of the 2024 – 2025 COVID -19 vaccine or require \nconsiderations when implementing it?\n• Is access to a second dose of the 2024 – 2025 COVID -19 vaccine an \nimportant concern?\noNo oProbably no oProbably yes oYes oVaries oDon’t know\n88\nFeasibility \nAre additional doses (i.e., 3 or more) of the 2024 – 2025 COVID -19 vaccine \nfeasible to implement among persons with moderate or severe \nimmunocompromise ?\n• Are additional doses of the 2024 – 2025 COVID -19 vaccine program \nsustainable?\n• Are there barriers that are likely to limit the feasibility of implementing \nadditional doses of the 2024 – 2025 COVID -19 vaccine or require \nconsiderations when implementing it?\n• Is access to additional doses of the 2024 – 2025 COVID -19 vaccine an \nimportant concern?\noNo oProbably no oProbably yes oYes oVaries oDon’t know\n88\nEtR Domain:\nResource Use \n90\n91\n92\nDomain Equity Question: \nIs the intervention a reasonable and efficient allocation of resources \nacross all populations? \n93\n•A second dose of COVID -19 vaccine is most cost -effective in older adults in \nwhom disease burden is highest. \n•A second dose of COVID -19 vaccine is likely more cost -effective in \npopulations with a higher prevalence of risk factors, such as underlying \nconditions, which increase their probability of hospitalization due to \nCOVID -19.\n-We do not have information specific to cost effectiveness of additional doses in \npeople with moderate or severe immunocompromiseIs the intervention a reasonable and efficient \nallocation of resources across all populations?\nEquity 94\n•Second dose of 2024 –2025 COVID -19 vaccine in adults 65 and older \n-Base case ICER: $356,534/QALY\n•For all COVID -19 vaccines, if list prices were reduced, vaccination would be \nmore cost -effectiveSummary\nResource Use\nQALY: Quality- adjusted life year95\nResource Use  \nIs a second dose of the 2024 – 2025 COVID -19 vaccine in adults ≥65 years  a \nreasonable and efficient allocation of resources?\n• What is the cost- effectiveness of a second dose of the 2024 – 2025 COVID -\n19 vaccine?\n• How does the cost -effectiveness of a second dose of the 2024 – 2025 \nCOVID -19 vaccine change in response to changes in context, assumptions, \netc.?\noNo oProbably no oProbably yes oYes oVaries oDon’t know\n96\nResource Use  \nIs a second dose of the 2024 – 2025 COVID -19 vaccine in persons ≥6 months \nof age with moderate or severe immunocompromise a reasonable and \nefficient allocation of resources?\n• What is the cost- effectiveness of a second dose of the 2024 – 2025 COVID -\n19 vaccine?\n• How does the cost -effectiveness of a second dose of the 2024 – 2025 \nCOVID -19 vaccine change in response to changes in context, assumptions, \netc.?\noNo oProbably no oProbably yes oYes oVaries oDon’t know\n97\nResource Use  \nAre additional doses (i.e., 3 or more) of the 2024 – 2025 COVID -19 vaccine in \npersons ≥6 months of age with moderate or severe immunocompromise a \nreasonable and efficient allocation of resources?\n• What is the cost- effectiveness of additional doses of the 2024 – 2025 \nCOVID -19 vaccine?\n• How does the cost -effectiveness of additional doses of the 2024 – 2025 \nCOVID -19 vaccine change in response to changes in context, assumptions, \netc.?\noNo oProbably no oProbably yes oYes oVaries oDon’t know\nMinority Opinion98\nWork Group Interpretations \n99\nWork Group Interpretation\n•A harmonized recommendation for older adults and immunocompromised persons \nwould ease implementation and help simplify an already complicated immunization \nschedule\n-Some work group members were not in favor of a harmonized recommendation but rather \nsupported having differing recommendations in the two populations under consideration\n•Relative absence of data makes selecting the correct number of recommended doses \nchallenging for immunocompromised persons, especially given the heterogeneity of this population\n•Despite hesitations about a shared clinical decision- making recommendation, many \nWork Group members acknowledged the benefit for people with moderate or severe immunocompromise\n-Allowing for flexibility in additional doses may allow these patients to time around travel, life \nevents, chemotherapy, etc. \n100\nWork Group Interpretation \n•There was low uptake of more than one dose of 2023– 2024 vaccine\n-Complexity of existing schedule has led to reduced adherence by clinicians\n•Provider recommendations directly impact uptake, and as part of this \nrecommendation, provider education and ensuring providers are on board is critical to improving adherence\n•While simpler vaccine recommendations aren’t perfect, there may be benefits in increasing vaccine uptake, and enhancing protection at the population level\n•Focusing on number of doses of 2024– 2025 vaccine rather than additional doses in \nrecommendations could help reduce complexity and improve uptake\n101\nEtR Domain​​​ ​​Question​ Work Group Judgments\nPublic Health \nProblem​​​Is COVID -19 disease among older adults of public health importance? Yes\nBenefits and \nHarmsHow substantial are the desirable anticipated effects? Moderate/Large\nHow substantial are the undesirable anticipated effects? Minimal/Small\nDo the desirable effects outweigh the undesirable effects? Favors intervention \nValues​​​Do older adults feel that the desirable effects are large relative to undesirable \neffects?Moderate\nIs there important uncertainty about, or variability in, how older adults value the main outcomes?Probably important uncertainty or variability/Probably not important \nuncertainty or variability \nAcceptability​​​Would recommending a second dose of the 2024 –2025 COVID -19 vaccine for \nolder adults be acceptable to key stakeholders?Probably yes/Yes\nFeasibility​​​Is a second dose of the 2024 –2025 COVID -19 vaccine feasible to implement \namong older adults?​​​Probably yes/Yes\nResource Use​​​Is a second dose the 2024 –2025 COVID -19 vaccine in older adults a reasonable \nand efficient allocation of resources?​​​Probably yes/Yes Work Group Judgements - a second dose of 2024 –2025 COVID -19 \nvaccine in adults ≥65 years \n102\nEvidence to Recommendations Framework\nSummary: Work Group Interpretations -  a second dose of 2024 –\n2025 COVID -19 vaccine in adults ≥65 years \nBalance of \nconsequencesUndesirable \nconsequences \nclearly outweigh \ndesirable \nconsequences \nin most settingsUndesirable \nconsequences \nprobably \noutweigh \ndesirable \nconsequences \nin most settingsThe balance \nbetween \ndesirable and \nundesirable \nconsequences \nis closely \nbalanced or \nuncertainDesirable \nconsequences \nprobably \noutweigh \nundesirable \nconsequences \nin most settingsDesirable \nconsequences \nclearly \noutweigh \nundesirable \nconsequences \nin most settingsThere is \ninsufficient \nevidence to \ndetermine the \nbalance of \nconsequences\nMajority Opinion Minority Opinion 103\nIs there sufficient information to move forward with a recommendation?Evidence to Recommendations Framework\nSummary: Work Group Interpretations -  a second dose of 2024 –\n2025 COVID -19 vaccine in adults ≥65 years\nYes No\n104\nEvidence to Recommendations Framework\nSummary: Work Group Interpretations - a second dose of \n2024– 2025 COVID -19 vaccine in adults ≥65 years\nType of \nrecommendationWe do not recommend \nthe interventionWe recommend the \nintervention for individuals \nbased on shared clinical \ndecision -makingWe recommend the \nintervention \n105\nEtR Domain​​​ ​​Question​ Work Group Judgments\nPublic Health \nProblem​​​Is COVID -19 disease among persons ≥6 months of age with moderate or severe \nimmunocompromise of public health importance?Yes\nBenefits and HarmsHow substantial are the desirable anticipated effects? Moderate\nHow substantial are the undesirable anticipated effects? Minimal/Small\nDo the desirable effects outweigh the undesirable effects? Favors intervention\nValues​​​Do persons ≥6 months of age with moderate or severe immunocompromise feel that the desirable \neffects are large relative to undesirable effects?Moderate/Large\nIs there important uncertainty about, or variability in, how persons ≥6 months of age with moderate or severe immunocompromise value the main outcomes?Probably important uncertainty or \nvariability/Probably not important \nuncertainty or variability  \nAcceptability​​​Would recommending an additional dose of the 2024 –2025 COVID -19 vaccine for persons ≥6 \nmonths of age with moderate or severe immunocompromise be acceptable to key stakeholders?Probably yes/Yes\nFeasibility​​​Is an additional dose of the 2024 –2025 COVID -19 vaccine feasible to implement among persons ≥6 \nmonths of age with moderate or severe immunocompromise ?​​​Probably yes/Yes\nResource Use​​​Is an additional dose the 2024 –2025 COVID -19 vaccine in persons ≥6 months of age with moderate \nor severe immunocompromise a reasonable and efficient allocation of resources?​​​Probably yes/Yes Work Group Judgements - a second dose of 2024 –2025 COVID -19 vaccine in people \nages ≥6 months with moderate or severe immunocompromise \n106\nEvidence to Recommendations Framework\nSummary: Work Group Interpretations - second dose in \npeople ages ≥6 months with moderate or severe \nimmunocompromise \nBalance of \nconsequencesUndesirable \nconsequences \nclearly outweigh \ndesirable \nconsequences \nin most settingsUndesirable \nconsequences \nprobably \noutweigh \ndesirable \nconsequences \nin most settingsThe balance \nbetween \ndesirable and \nundesirable \nconsequences \nis closely \nbalanced or \nuncertainDesirable \nconsequences \nprobably \noutweigh \nundesirable \nconsequences \nin most settingsDesirable \nconsequences \nclearly \noutweigh \nundesirable \nconsequences \nin most settingsThere is \ninsufficient \nevidence to \ndetermine the \nbalance of \nconsequences\nMajority Opinion Minority Opinion 107\nIs there sufficient information to move forward with a recommendation?Evidence to Recommendations Framework\nSummary: Work Group Interpretations – a second dose \nin people ages ≥6 months with moderate or severe \nimmunocompromise \nYes No\n108\nEvidence to Recommendations Framework\nSummary: Work Group Interpretations - a second dose \nin people ages ≥6 months with moderate or severe \nimmunocompromise \nType of \nrecommendationWe do not recommend \nthe interventionWe recommend the \nintervention for individuals \nbased on shared clinical \ndecision -makingWe recommend the \nintervention \n109\nEtR Domain​​​ ​​Question​ Work Group Judgments\nPublic Health \nProblem​​​Is COVID -19 disease among persons ≥6 months of age with moderate or severe \nimmunocompromise of public health importance?Yes\nBenefits and HarmsHow substantial are the desirable anticipated effects? Moderate\nHow substantial are the undesirable anticipated effects? Minimal/Small\nDo the desirable effects outweigh the undesirable effects? Favors intervention/Unclear\nValues​​​Do persons ≥6 months of age with moderate or severe immunocompromise feel that the desirable \neffects are large relative to undesirable effects?Moderate/Large\nIs there important uncertainty about, or variability in, how persons ≥6 months of age with moderate or severe immunocompromise value the main outcomes?Probably important uncertainty or \nvariability/Probably not important \nuncertainty or variability  \nAcceptability​​​Would recommending additional doses (i.e., 3 or more) of the 2024 –2025 COVID -19 vaccine for \npersons ≥6 months of age with moderate or severe immunocompromise be acceptable to key stakeholders?Probably yes/Yes\nFeasibility​​​Are additional doses (i.e., 3 or more) of the 2024 –2025 COVID -19 vaccine feasible to implement \namong persons ≥6 months of age with moderate or severe immunocompromise ?​​​Probably yes/Yes\nResource Use​​​Are additional doses (i.e., 3 or more) of the 2024 –2025 COVID -19 vaccine in persons ≥6 months of \nage with moderate or severe immunocompromise a reasonable and efficient allocation of \nresources?​​​Varies Work Group Judgements - additional doses (i.e., 3 or more) of 2024 –2025 COVID -19 \nvaccine in people ages ≥6 months with moderate or severe immunocompromise \n110\nEvidence to Recommendations Framework\nSummary: Work Group Interpretations - Additional \ndoses (i.e., 3 or more) in people ages ≥6 months with \nmoderate or severe immunocompromise \nBalance of \nconsequencesUndesirable \nconsequences \nclearly outweigh \ndesirable \nconsequences \nin most settingsUndesirable \nconsequences \nprobably \noutweigh \ndesirable \nconsequences \nin most settingsThe balance \nbetween \ndesirable and \nundesirable \nconsequences \nis closely \nbalanced or \nuncertainDesirable \nconsequences \nprobably \noutweigh \nundesirable \nconsequences \nin most settingsDesirable \nconsequences \nclearly \noutweigh \nundesirable \nconsequences \nin most settingsThere is \ninsufficient \nevidence to \ndetermine the \nbalance of \nconsequences\n111\nIs there sufficient infromation to move forward with a recommendation?Evidence to Recommendations Framework\nSummary: Work Group Interpretations - additional \ndoses (i.e., 3 or more) in people ages ≥6 months with \nmoderate or severe immunocompromise \nYes No\n112\nEvidence to Recommendations Framework\nSummary: Work Group Interpretations - additional \ndoses (i.e., 3 or more) in people ages ≥6 months with \nmoderate or severe immunocompromise \nType of \nrecommendationWe do not recommend \nthe interventionWe recommend the \nintervention for individuals \nbased on shared clinical \ndecision -makingWe recommend the \nintervention \n113\nACIP Voting Language\n In addition to previously recommended 2024 –2025 vaccination: \n•ACIP recommends a second dose* of 2024– 2025 COVID -19 vaccine for \nadults ages 65 years and older\n•ACIP recommends a second dose**  of 2024– 2025 COVID -19 vaccine for \npeople ages 6 months –64 years who are moderately or severely \nimmunocompromised\n•ACIP recommends additional doses (i.e., 3 or more doses) of 2024–\n2025 COVID -19 vaccine for people ages 6 months and older who are \nmoderately or severely immunocompromised under shared clinical \ndecision -making\n*If previously unvaccinated and receiving Novavax, 2 doses are recommended as initial vaccination series followed by a third dos e of any age -appropriate 2024- 2025 COVID -19vaccine 6 \nmonths (minimum interval 2 months) after second dose​.\n**If previously unvaccinated or receiving initial vaccination series, at least 2 doses of 2024 –2025 vaccine are recommended, and  depending on vaccination history more may be needed. \nThis additional 2024– 2025 vaccine dose is recommended 6 months (minimum interval 2 months) after completion of initial vaccinati on series.​114\nAcknowledgements\n•Kayla Calhoun\n•Mary Chamberland\n•Kevin Chatham -Stephens\n•Jonathan Duffy\n•Tarayn Fairlie\n•Katherine Fleming -Dutra\n•Julianne Gee \n•Monica Godfrey\n•Susan Goldstein\n•Aron Hall\n•Elisha Hall\n•Fiona Havers•Jefferson Jones\n•Jennifer Kriss\n•Megan Lindley\n•Ruth Link -Gelles\n•Danielle Moulia\n•Lakshmi Panagiotakopoulos\n•Georgina Peacock\n•Erica Rose\n•Sierra Scarbrough\n•Ben Silk\n•Chris Taylor\n•Natalie Thornburg•Megan Wallace\n•Dave Wentworth\n•JoEllen Wolicki\n•Coronavirus and other Respiratory \nViruses Division\n•COVID -NET Team\n•Immunization Safety Office\n•Immunization Services Division\n•National Center for Immunization and Respiratory Diseases\n•University of Michigan COVID -19 \nVaccination Modeling Team\n115\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the U.S. Centers for Disease Control and Prevention.\nThank you\nBackup \n117\nWeighted and Nowcast Estimates in the US for 2 -week \nperiods, June 23 –October 12, 2024\n** These data include Nowcast estimates, which are modeled projections that may differ from weighted estimates generated at l ater dates\nhttps://covid.cdc.gov/covid -data -tracker/#variant -proportions  121", "summary": "Evidence to Recommendations Framework: Additional Doses of 2024– 2025 COVID -19 Vaccine in Older Adults and  People with Moderate or Severe Immunocompromise   Ms. Lauren Roper, MPH COVID -19 ACIP Work Group co -lead Advisory Committee on Immunization Practices Meeting October 23, 2024National Center for Immunization and Respiratory Diseases   •On June 27, 2024, ACIP voted to recommend 2024 –2025 COVID -19  vaccines for everyone ages 6 months and older  •On August 22, 2024, FDA approved and…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-23-24-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/06-COVID-Roper-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 118}
{"title": "07 COVID Panagiotakopoulos 508", "content": "Clinical Considerations for the use of 2024 -2025 \nCOVID -19 Vaccines in the United States\nLakshmi Panagiotakopoulos, MD, MPH\nCOVID -19 ACIP Work Group co -lead\nAdvisory Committee on Immunization Practices Meeting\nOctober 23, 2024National Center for Immunizations and Respiratory Diseases \n•On June 27, 2024, ACIP recommended 2024 -2025 COVID -19 vaccination for \neveryone ages 6 months and older \n•On August 22, 2024, FDA approved and authorized Moderna and Pfizer -\nBioNTech 2024 -2025 COVID -19 vaccines \n•On August 30, 2024, FDA authorized Novavax 2024 -2025 COVID -19 vaccine\n•The Interim Clinical Considerations for Use of COVID -19 vaccines webpage \nwas updated with detailed recommendations\n•A Policy Note outlining the recommendations was published in the \nMMWR on September 10, 2024Current  2024 -2025 COVID -19 vaccine \nrecommendations  \nhttps://www.cdc.gov/vaccines/covid -19/clinical -considerations/covid -19-vaccines -us.html  \nhttps://www.cdc.gov/mmwr/volumes/73/wr/mm7337e2.htm  \nACIP: Advisory Committee on Immunization Practices | FDA: Food and Drug Administration | MMWR: Morbidity and Mortality Weekly  Report 2\n•Use of 2024- 2025 COVID -19 vaccine: Routine schedule\n-Proposed  recommendations for a second dose in adults ages 65 \nyears and older\n•Use of 2024- 2025 COVID -19vaccine: People with moderate or severe \nimmunocompromise\n-Proposed  recommendations for use of additional dose(s) in people \nwith moderate or severe immunocompromise\n•Updates to clinical considerations Outline\n3\nRoutine schedule\nPeople without  moderate or severe immunocompromise\n•All doses should be homologous (i.e., from the same manufacturer) Current  recommendations for children ages 6 months –  4 years \nDoses recommended:\nInitial series of 2 Moderna vaccine doses OR 3 Pfizer-\nBioNTech vaccine doses \nAt least 1 dose of 2024– 2025 COVID -19 vaccine, as part of \nor in addition to initial series  \n5\n•2024– 2025 COVID -19 vaccine dose is recommended at least 2 months after receipt of the \nlast COVID -19 vaccine dose\n•mRNA COVID -19 vaccines authorized or approved for ages 6 months and older and \nNovavax COVID -19 vaccine authorized for ages 12 years and older\n•People who are previously unvaccinated for COVID -19 and are receiving Novavax should \ncomplete a 2 -dose initial seriesCurrent  recommendations for people ages 5 years and older \nDoses recommended:\n•1 dose of 2024- 2025 COVID -19 vaccine\n6\n•2024– 2025 COVID -19 vaccine dose is recommended at least 2 months after receipt of the \nlast COVID -19 vaccine dose\n•mRNA COVID -19 vaccines authorized or approved for ages 6 months and older and \nNovavax COVID -19 vaccine authorized for ages 12 years and older\n•People who are previously unvaccinated for COVID -19 and are receiving Novavax should \ncomplete a 2 -dose initial seriesProposed  recommendations for people ages 5 –  64 years\nDoses recommended:\n•1 dose of 2024- 2025 COVID -19 vaccine\n7\nProposed recommendations for adults ages 65 years and older \n•If previously unvaccinated and receiving Novavax, 2 doses are recommended as \ninitial vaccination series followed by a third dose of any age -appropriate 2024- 2025 \nCOVID -19 vaccine 6 months (minimum interval 2 months) after second dose​.\n8Doses recommended:\n•2 doses of 2024- 2025 COVID -19 vaccine\n•Recommended interval 6 months (minimum interval 2 months)\nRecommendations for people with \nmoderate or severe immunocompromise\nCurrent  recommendations for people ages 6 months and older \nwho are moderately or severely immunocompromised\nDoses recommended:\nInitial COVID -19 vaccine series*\nAt least 1 2024– 2025 COVID -19 vaccine dose\nMay receive 1 additional 2024 -2025 COVID -19 \nvaccine dose with option for further additional \ndoses of 2024- 2025 COVID -19 vaccine**\n*Series of 3 homologous mRNA COVID -19 vaccine doses or 2 Novavax COVID -19 vaccine doses (if ages 12 years and older); includes revaccination after \nhematopoietic cell transplant and CAR -T-cell, or B -cell- depleting therapies. \n**Further additional dose(s) may be administered, informed by the clinical judgement of a healthcare provider and personal prefe rence and \ncircumstances. Further additional doses should be administered at least 2 months after the last 2024 -2025 COVID -19 vaccine dose.  \nFor more information, see  https://www.cdc.gov/vaccines/covid -19/clinical -considerations/interim- considerations -us.html#immunocompromised .\n10\nProposed  recommendations for people ages 6 months and \nolder who are moderately or severely immunocompromised\nDoses recommended:\nInitial COVID -19 vaccine series*\nAt least 2 2024– 2025 COVID -19 vaccine doses**\nRecommended interval 6 months (minimum interval 2 months)\nAdditional 2024 -2025 COVID -19 vaccine doses under \nshared clinical decision making***\n*Series of 3 homologous mRNA COVID -19 vaccine doses or 2 Novavax COVID -19 vaccine doses (if ages 12 years and older); includes revaccination after \nhematopoietic cell transplant and CAR -T-cell, or B -cell- depleting therapies. \n**One 2024- 2025 COVID -19 vaccine dose may be received as part of the initial vaccination series and at least one of the two doses should be received 6 \nmonths (minimum interval 2 months) after completion of the initial series.  \n***Additional doses should be administered at least 2 months after the last 2024 -2025 COVID -19 vaccine dose. \nFor more information, see  https://www.cdc.gov/vaccines/covid -19/clinical -considerations/interim- considerations -us.html#immunocompromised . \n11\nUpdates to Clinical Considerations\n•Age transitions\n•Interchangeability of COVID -19 vaccines\n•COVID -19 vaccination and prior SARS -CoV -2 infectionClinical considerations \n13\n•CDC recommends that people receive the age -appropriate vaccine product \nand dosage based on their age on the day of vaccination.\n•If a person moves to an older age group between vaccine doses, they \nshould receive the vaccine product and dosage for the older age group. For children who transition from age 4 years to age 5 years and children who are moderately or severely immunocompromised and transition from age 11 years to age 12 years, the option to administer a lower dosage is no longer authorized.Transitioning from a younger to older age group\nhttps://www.cdc.gov/vaccines/covid -19/clinical -considerations/interim -considerations -us.html#age -transitions  14\n•COVID -19 vaccine doses from the same manufacturer should be \nadministered whenever recommended. In the following circumstances, an \nage-appropriate COVID -19 vaccine from a different manufacturer may be \nadministered:\n-Same vaccine not available at the vaccination site at the time of the clinic visit \n-Previous dose unknown\n-Person would otherwise not receive a recommended vaccine dose\n-Person starts but unable to complete a vaccination series with the same COVID- 19 \nvaccine due to a contraindication\nA Vaccine Adverse Event Reporting System (VAERS) report is not indicated in these \ncircumstances.Interim Clinical Considerations on interchangeability of \nCOVID- 19 vaccines\n15 https://www.cdc.gov/vaccines/covid -19/clinical -considerations/interim -considerations -us.html#Interchangeability  \n•People ages 12 years and older who are initiating vaccination with \nNovavax COVID -19 Vaccine (i.e., previously unvaccinated) and \nreceive a first dose of Novavax should complete the 2 -dose initial \nvaccination series with Novavax vaccine. \n•However, if more than 8 weeks have elapsed since receipt of the \nfirst dose of Novavax, any 2024– 2025 COVID -19 vaccine (i.e., \nModerna, Novavax, or Pfizer -BioNTech) may be administered.Additional guidance: Interim Clinical Considerations on \ninterchangeability of COVID- 19 vaccines – Novavax* \n16 https://www.cdc.gov/vaccines/covid -19/clinical -considerations/interim -considerations -us.html#Interchangeability  *For people who are not moderately or severely immunocompromised \n•COVID -19 vaccination is recommended for everyone ages 6 months and \nolder, regardless of prior symptomatic or asymptomatic SARS -CoV -2 \ninfection, including people with Long COVID.\n•People who recently had SARS -CoV -2 infection may consider delaying a \nCOVID -19 vaccine dose by 3 months from symptom onset or positive test \n(if infection was asymptomatic).\n•Individual factors such as risk of severe COVID -19 and current indicators of \ncommunity transmission should be taken into account when determining \nwhether to delay getting a COVID -19 vaccination after infection.Reminder: COVID -19 vaccine and prior SARS -CoV-2 \ninfection\nhttps://www.cdc.gov/vaccines/covid -19/clinical -considerations/interim -considerations -us.html#infection  17\nSummary\n•Children ages 6 months –4 years\n-Unvaccinated: Should receive a multidose initial series with a 2024 –2025 mRNA \nvaccine\n-Previously completed an initial series: Should receive 1 dose of a 2024 –2025 \nmRNA vaccine from the same manufacturer as the initial series\n•People ages 5 –64 years: \n-Should receive 1 dose of an age- appropriate 2024 -2025 COVID -19 vaccine* \n•People ages 65 years and older: \n-Should receive 2 doses of any 2024 –2025 COVID -19 vaccine, spaced 6 months \napart (minimum interval 2 months)**Overview of the COVID -19 vaccination schedule: \nRoutine vaccination\n*People ages 12 -64 years who are unvaccinated and receive the 2024 -2025 Novavax COVID -19 vaccine for initial vaccination should receive 2 doses of 2024- 2025 Novavax COVID -19 vaccine. \n**People ages 65 years and older who are unvaccinated and receive Novavax COVID -19 Vaccine for initial vaccination should receiv e 2 doses of 2024– 2025 Novavax COVID -19 vaccine followed by a \nthird dose of any 2024 –2025 COVID -19 vaccine dose 6 months after the second dose (minimum interval 2 months). 19\n•Unvaccinated: \n-Should receive a multidose vaccination series with an age -appropriate 2024– 2025 \nvaccine and receive 1 2024– 2025 dose 6 months after completing the initial series \n(minimum interval 2 months)\n•Previously completed an initial series: \n-Should receive 2 doses of an age -appropriate 2024– 2025 COVID -19 vaccine, \nspaced 6 months apart (minimum interval 2 months) \n•May receive additional age -appropriate 2024 –2025 COVID -19 vaccine \ndoses under shared clinical decision -makingOverview of the COVID -19 vaccination schedule: \nModerate or severe immunocompromise\n20\n•Interim Clinical Considerations for Use of COVID -19 Vaccines in the United \nStates webpage continues to be rapidly updated to reflect the most recent \nCOVID -19 vaccine guidance\n•COVID -19 vaccine recommendations have moved towards simplicity and \nthe standard language used for the ACIP routine immunization schedules \nand General Best Practices\n•Recommendations for use of additional doses in older adults and people \nwith moderate or severe immunocompromise will be updated following the October 2024 ACIP meeting votesSummary \nhttps://www.cdc.gov/vaccines/covid -19/clinical -considerations/covid -19-vaccines -us.html  21\n•Mary Chamberland\n•Katherine Fleming -Dutra\n•Susan Goldstein\n•Elisha Hall\n•Lauren Roper\n•JoEllen Wolicki •Coronavirus and other Respiratory \nViruses Division\n•Immunization Safety Office\n•Immunization Services Division\n•National Center for Immunization and \nRespiratory Diseases\n•ACIP COVID -19 Work GroupAcknowledgements \n22\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.", "summary": "Clinical Considerations for the use of 2024 -2025  COVID -19 Vaccines in the United States Lakshmi Panagiotakopoulos, MD, MPH COVID -19 ACIP Work Group co -lead Advisory Committee on Immunization Practices Meeting October 23, 2024National Center for Immunizations and Respiratory Diseases  •On June 27, 2024, ACIP recommended 2024 -2025 COVID -19 vaccination for  everyone ages 6 months and older  •On August 22, 2024, FDA approved and authorized Moderna and Pfizer - BioNTech 2024 -2025 COVID -19…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-23-24-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/07-COVID-Panagiotakopoulos-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 23}
{"title": "01 RSV Mat Peds Chu 508", "content": "Maternal/Pediatric Respiratory Syncytial Virus (RSV) \nWork Group​\nHelen Chu, MD, MPH\nChair, Maternal/Pediatric RSV Work Group  \nACIP Meeting\nOctober 23, 2024 \n1U.S. Centers for Disease Control and Prevention\n\nAll infants should be protected against severe RSV disease \nwith either maternal RSV vaccine or nirsevimab\nMaternal vaccine\nAbrysvo , Pfizer  \n*Either  maternal RSV vaccine or nirsevimab  is given to protect infants against severe RSV \ndisease – only one is needed in most instances \nPregnant persons 32 through \n36 weeks’ gestation\nAdminister September \nthrough January in most of \nthecontinental United \nStates†All infants <8 months* \nSecond season dose for children \nages 8 –19 months at increased \nrisk of severe RSV disease \nAdminister October through \nMarch in most of the continental \nUnited States † (earlier the \nbetter)\n† Timing of administration for RSV immunization may differ in jurisdictions with RSV seasonality that differs from most of the continental United StatesNirsevimab\nBeyfortus , Sanofi & AstraZeneca \nNirsevimab  and maternal vaccination have different \nadministration windows to provide optimal protection \nto the infant\nForinfants born shortly before October, or during October through March who are not \nprotected by maternal RSV vaccine, immunize within 1 week of birth, ideally during the \nbirth hospitalization\n•Safety and efficacy of clesrovimab  — Dr. Anushua Sinha (Merck) \n•Maternal RSV vaccine safety — Dr. Malini B. DeSilva (Health Partners \nInstitute) \n•Work Group considerations — Ms. Danielle Moulia (CDC/NCIRD)Agenda\n4\nWork group members (external)\nACIP Members\nHelen Chu (chair)\nOliver Brooks\nDenise JamiesonConsultants\nCody Meissner (Dartmouth Geisel School of Medicine)\nDaniel Feikin  (World Health Organization)\nKevin Ault (Western Michigan University)\nPablo Sanchez (Nationwide Children’s Hospital)\nLiaisons\nJames McAuley (IDSA)\nBrenna Hughes (ACOG)\nNicole Chaisson  (AAFP)\nSean O’Leary (AAP)\nJennifer Schuster (PIDS)\nMolly Howell (AIM)\nDana DeShon  (NAPNAP)GRADE/ EtRConsultants\nDoug Campos -Outcalt\nRebecca MorganEx Officio Members\nLucia Lee (FDA -CBER)\nYodit Belew (FDA -CDER)\nPrabha Viswanathan (FDA -CDER)\nYugenia Hong -Nguyen (FDA -CDER)\nSonnie Kim (NIH -NIAID)\nApril Killikelly (Public Health Agency of Canada)\nElissa Abrams  (Public Health Agency of Canada)\nJessica Lee (CMS/CMCS)\nTerry Dalle -Tezze (HRSA)\nMatthew Clark (IHS)\n5\nWork group members (CDC)\nTami Skoff\nAngie Campbell\nMichael Melgar\nAmadea Britton\nAmanda Payne\nNoelle Molinari\nFiona Havers\nPragna PatelRuth Link -Gelles\nMonica Godfrey\nHeidi Moline\nHannah Rosenblum\nManisha Patel\nHeather Scobie\nMichele Hlavsa CDC ACIP Staff\nMelinda Wharton\nStephanie Thomas\nJessica MacNeilMonica Patton\nJarrett Gartin\nDennis Wang\nJordan Singleton\nTrang Nguyen Wisard\nFatimah Dawood\nAgustin Lopez\nLakshmi PanagiotakopoulosCDC\nJefferson Jones (co -lead)\nDanielle Moulia (co -lead)\nKatherine Fleming -Dutra \nMeredith McMorrow\nMila Prill\nNatalie Thornburg\nAron Hall\nIsmael Ortega -Sanchez\nMelissa Coughlin\nJamison Pike\nLauren RoperA. Patricia Wodi\nChristine Olson\nAnne Hause\nAndrew Leidner\nDavid Shay\nSarah Meyer\nPedro Moro\nTarayn Fairlie\nJohn Su\nMicheal McNeal\nJulianne Gee \nNaomi Tepper\n6\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position \nof the U.S. Centers for Disease Control and Prevention.\nThank you", "summary": "Maternal/Pediatric Respiratory Syncytial Virus (RSV)  Work Group​ Helen Chu, MD, MPH Chair, Maternal/Pediatric RSV Work Group   ACIP Meeting October 23, 2024  1U.S. Centers for Disease Control and Prevention  All infants should be protected against severe RSV disease  with either maternal RSV vaccine or nirsevimab Maternal vaccine Abrysvo , Pfizer   *Either  maternal RSV vaccine or nirsevimab  is given to protect infants against severe RSV  disease – only one is needed in most instances …", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-23-24-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/01-RSV-Mat-Peds-Chu-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 7}
{"title": "02 RSV Mat Peds Sinha 508", "content": "Clesrovimab  (MK-1654): \nPediatric  Clinical  Program\nPresentation  to the Advisory  Committee  on Immunization  Practices\nAnushua  Sinha,  MD, MPH\nClinical  Director  -Vaccines  Clinical  Research \nMerck  & Co., Inc.\nRahway,  NJ, USA\nOctober  23, 2024\nConfidential\nClesrovimab  is a human  monoclonal  antibody  with four unique  molecular \ncharacteristics  that enable  robust  and durable  protection  from  RSV\n2Notes: a. Clesrovimab  is ~50-fold more  potent  in vitro than palivizumab;  Abbreviations : F=Fusion;  RSV=Respiratory  Syncytial  Virus;  Sources : 1. Tang  A et al. Nat Commun . 2019;  2. RSV GeneBank  sequences \nas of April 1, 2024;  3. Phuah  JY et al. Biomed  Pharmacother.  2023.\nClesrovimabRSV Prefusion  F protein\nSite IVBinds  with high affinity  to site IV of RSV  F protein,  \nprevents  fusion  of virus  to host cells  and blocks  entry  to \nprovide  direct  protection1\n̶  Binding  epitope  on site IV is highly  conserved , with 99.8% identity  \namong  >15,000 reported  RSV-A and RSV-B sequences2\nHigh  potency  in vitro and equipotent  against  RSV-A and RSV-Ba\nYTE substitutions  enable  extended  half-life (~44  days)\n4\nAchieves  high nasal  tissue  distribution  and concentrations  at sites \nof RSV infection32\n31\nSite IV\nClesrovimab\nConfidential\n➢Prevention  of respiratory  syncytial  virus  (RSV)  lower  respiratory  tract \ndisease  in neonates  and infants  who are born  during  or entering  their  first \nRSV seasonProposed  Indication  and Dosing\n3Proposed  Indication\n➢105 mg/0.7  mL administered  as a single  intramuscular (IM)  injection\n➢Clesrovimab  dosing  is the same  for all infants  regardless  of weightProposed  Dosing  and \nAdministration\nConfidential\nClesrovimab  Clinical  Development  Program\n4\nPhase  1:\nSafety  and PK – adults\nPhase  1b/2a:\nSafety  and PK – infants\nPhase  2b/3:\nEfficacy,  safety  and PK – \ninfants  & childrenPhase  1 – Adults\n(Protocol  001)1\nCompleted\nPhase  1b/2a – Infants  (Protocol  002)3\nCompleted\n2017 2018 2019 2020 2021 2022 2023Currently \nhere\nAbbreviations:  PK=Pharmacokinetics;  RSV=Respiratory  Syncytial  Virus;  Sources:  1. Aliprantis  AO et al. Clin Pharmacol  Drug  Dev. 2021;10(5):556 -566; 2. Orito Y et al. Clin Transl  Sci. 2022;15(7):1753 -1763;\n3. Madhi  SA, Simoes  EAF,  Acevedo  A, et al. A phase  1b/2a  single -ascending -dose  study  to evaluate  the safety,  tolerability,  and pharmacokinetics  of an RSV-neutralizing  antibody,  clesrovimab,  in preterm \nand full-term  infants.  Oral and Poster  presentation.  8th ReSViNET  Conference  February  13-16, 2024  Mumbai,  India;  4. clinicaltrials.gov  (NCT04767373);  5. clinicaltrials.gov  (NCT04938830).Phase  1 – Adults\n(Protocol  003)2\nCompletedPhase  1 – Adults,  Infants \n& Children  (Protocol  008)\nCompleted\nPhase  2b/3  – Infants  (Protocol  004)4\nCompleted\nPhase  3 – Infants  & Children (Protocol  007)5\nOngoing\n2024\n\nProtocol  004:\nA Phase  2b/3 Double -Blind,  Randomized,  Placebo -Controlled \nStudy  to Evaluate  the Efficacy  and Safety  of Clesrovimab  in \nHealthy  Preterm  and Full-Term  Infants\nConfidential\nProtocol  004:  Study  Design\nPhase  2b/3 randomized,  double -blinded,  placebo -controlled  with active RSV surveillance  through  6 months\nObjective:  Efficacy  and safety  of clesrovimab  in healthy  preterm  and full-term  infants  entering  their  first RSV season\n▪Phase  2b cohort : First  300 infants  enrolled\n▪Phase  3 cohort : Seamless  enrollment  following  Phase  2b cohort\nExperimental  Arm\nComparator  ArmRSV-Associated  Efficacy\n•MALRI ≥  1 Indicator of LRI/Severity  (primary)\n•Hospitalization  (secondary)\n•Acute  Respiratory  Infection (ARI)b (tertiary)\n•Lower  Respiratory  Infection  Hospitalization \n(tertiary)\n•Severe  MALRIc (tertiary)\n•MALRI  ≥ 2 Indicators  of LRI/Severity  (post -hoc)\nSafety\n•Adverse  Events  (AEs)\n•Serious  Adverse  Events  (SAEs)\nPlacebo\n0.9%  NaCl\n(N = 1,203)\nClesrovimab\n105 mg Single  IM dose \n(N = 2,411)\nRandomization \n2:1\n(N = 3,614)aAll RSV-Associated  \nEfficacy  Endpoints  \nfollowed  through  6 \nmonths  postdosedDay 1At Month  6 At Month  5\nNotes : a. N=Number  of randomized  participants,  dosed  with clesrovimab  or placebo ; b. ARI: Includes  both upper  and lower  respiratory  tract  infection ; c. Severe  MALRI : Severe  hypoxemia  (SpO 2 <90% on \nroom  air at sea level; <87% on room  air at altitude  ≥1800  m) or the need  for high flow nasal  cannula,  oxygen  mask,  or mechanical  ventilatory  support ; d. 6 month  endpoints  have  the same  designation  as 5 \nmonth  endpoints  aside  from  Hospitalization  through  6 months,  which  is a tertiary  endpoint,  and MALRI  ≥ 1 indicator  of LRI/Severity,  which  is a secondary  endpoint ; Abbreviations : ARI=Acute  Respiratory  \nInfection ; IM=Intramuscular ; LRI=Lower  Respiratory  Tract  Infection ; MALRI=Medically -Attended  Lower  Respiratory  Tract  Infection ; NaCl=Sodium  Chloride ; RSV=Respiratory  Syncytial  Virus .6First 1,650  infants \nenrolled  planned  for \nfollow -up through \nDay 515 postdose \n(second  RSV season)\nConfidential\nProtocol  004:  Baseline  Characteristics\n7Clesrovimab \nN = 2,411Placebo \nN = 1,203\nParticipants n (%) n (%)\nAge at Randomization  (Months)\n<6 1,923 (79.8) 964 (80.1)\n≥6 to <9 383 (15.9) 192 (16.0)\n≥9 105 (4.4) 47 (3.9)\nMean  (SD) 3.7 (2.6) 3.7 (2.6)\nMedian  (Range) 3.0 (0 to 12) 3.1 (0 to 12)\nBody  Weight  at Randomization  (kg)\nMean  (SD) 5.8 (2.0) 5.9 (2.0)\nMedian  (Range) 5.8 (1.6 to 11.9) 5.8 (1.6 to 11.6)\nGestational  Age\nEarly and Moderate  Preterm  Infant  (≥29 to <35 weeks) 422 (17.5) 209 (17.4)\nLate Preterm  and Full-term  Infant  (≥35 weeks) 1,989 (82.5) 994 (82.6)\nRace\nAmerican  Indian  Or Alaska  Native 50 (2.1) 18 (1.5)\nAsian 641 (26.6) 320 (26.6)\nBlack  Or African  American 326 (13.5) 171 (14.2)\nMultiple 302 (12.5) 138 (11.5)\nNative  Hawaiian  Or Other  Pacific  Islander 1 (0.0) 1 (0.1)\nWhite 1,082 (44.9) 550 (45.7)\nMissinga 9 (0.4) 5 (0.4)\nEthnicity\nHispanic  Or Latino 682 (28.3) 335 (27.8)\nNot Hispanic  Or Latino 1,660 (68.9) 834 (69.3)\nNot Reported,  Unknown,  or Missing 69 (2.9) 34 (2.8)\nSex\nMale 1,228 (50.9) 617 (51.3)\nFemale 1,183 (49.1) 586 (48.7)\nNote:  a. Includes  8 participants from  South  Africa  who have  race reported  as \"Colored\"  which  is not a standard  category  on the form;  Abbreviation: SD=Standard  Deviation.•Baseline  characteristics  of \ninfants  were  similar  in both \nclesrovimab  and placebo \narms\n•A total  of 3,614  healthy \ninfants  were  dosed\n•2,411  infants  received \nclesrovimab  and 1,203 \ninfants  received  placebo\n•Enrolled  a diverse \npopulation  across  race and \nethnicity  from  22\ncountries,  across  5 \ncontinents\n•631 participants  were \npreterm  infants  (≥29 to\n<35 weeks)\n•2,983  were  full-term \ninfants  (≥35 weeks)\nConfidential\nRSV-Associated  Endpointa\n(Through  5 months)Endpoint \nDesignationEfficacy  through  5 months\nClesrovimab \n(n = 2,398)Placebo \n(n = 1,201)Observed  Efficacy\n%, (95%  CI)\n# of Cases # of Cases\nSevere  MALRI Tertiary 2 12 91.7 (62.9,  98.1)\nLRI Hospitalization Tertiary 5 27 90.9  (76.2,  96.5)\nHospitalization Secondary 9 28 84.2d (66.6,  92.6)\nMALRI  requiring  ≥ 2 Indicators  of \nLRI/Severityb Post -Hoc 10 41 88.0  (76.1,  94.0)\nMALRI  requiring  ≥ 1 Indicator  of \nLRI/SeverityPrimary 60 74 60.4c (44.1,  71.9)\nAcute  Respiratory  Infection  (ARI) Tertiary 148 148 52.0 (39.5,  61.9)Protocol  004:  Efficacy\nSingle  dose of clesrovimab  protects  healthy  preterm  and full-term infants  against  mild,  moderate,  and severe  RSV \ndisease  through  5 months\n8Notes:  a. ARI and MALRI  include  both inpatient  and outpatient  cases;  b. MALRI  requiring  ≥ 2 indicators  of LRI/severity  endpoint  is most  comparable  to nirsevimab’s  primary  endpoint  in the MELODY  trial;\nc. Primary  endpoint,  p<0.001  (criterion=lower  bound  of the 95% CI >25%);  d. Secondary  endpoint,  p<0.001  (criterion=lower  bound  of the 95% CI >0%);  Abbreviations:  ARI=Acute  Respiratory  Infection; \nLRI=Lower  Respiratory Tract  Infection;  MALRI=Medically -Attended  Lower  Respiratory  Tract  Infection.Increasing  Disease  Severity\n\nConfidential\nRSV-Associated  Endpointa\n(Through  6 months )Endpoint \nDesignationEfficacy  through  6 months\nClesrovimab \n(n = 2,398)Placebo \n(n = 1,201)Observed  Efficacy\n%, (95%  CI)\n# of Cases # of Cases\nSevere  MALRI Tertiary 2 12 91.7 (62.9,  98.1)\nLRI Hospitalization Tertiary 5 28 91.2 (77.2,  96.6)\nHospitalization Tertiary 11 29 81.3 (62.5,  90.7)\nMALRI  requiring  ≥ 2 Indicators  of \nLRI/Severityb Post -Hoc 11 42 87.2 (75.1,  93.4)\nMALRI  requiring  ≥ 1 Indicator  of \nLRI/SeveritySecondary 64 77 59.5 (43.3,  71.1)\nAcute  Respiratory  Infection  (ARI) Tertiary 161 154 50.0  (37.4,  60.1)Protocol  004:  Efficacy\nDurable  across  all endpoints  through  6 months\n9Notes:  a. ARI and MALRI  include  both inpatient  and outpatient  cases;  b. MALRI  requiring  ≥ 2 indicators  of LRI/severity  endpoint  is most  comparable  to nirsevimab’s  primary  endpoint  in the MELODY  trial;\nAbbreviations:  ARI=Acute  Respiratory  Infection;  LRI=Lower  Respiratory  Tract  Infection;  MALRI=Medically -Attended  Lower  Respiratory  Tract  Infection.Increasing  Disease  Severity\n\nConfidential\nProtocol  004:  All-Cause  Endpoints\n10All-cause  Endpoint \n(Through  5 months \nPostdose)Clesrovimab \n(N = 2,411)Placebo \n(N = 1,203)Observed  Efficacy \n(%) Estimate  \n(95% CI)c\nnNumber \nof EventsTotal  Follow - \nUp Time \n(months)aIncidence \nRate  Over  5 \nmonthsb, %nNumber \nof EventsTotal  Follow - \nUp Time \n(months)aIncidence \nRate  over 5 \nmonthsb, %\nOutpatient  and \nInpatient  MALRI \ndue to any cause2,398 526 10,349.2 25.4 1,201 296 5,063.8 29.213.1\n(-0.6; 24.8)\nLRI Hospitalization \ndue to any cause2,398 60 11,711.8 2.6 1,201 58 5,774.0 5.049.0\n(26.7, 64.5)\nNotes:  a. One month  is defined  as 30 days  for the total follow -up time calculation;  b. Five months  is defined  as 150 days;  c. Estimate  and 95% CI of efficacy  were  estimated  from the modified  Poisson \nregression  with robust  variance  method;  Every  participant  is counted  a single  time for each applicable  endpoint  category;  A participant  may appear  in more  than one endpoint  category;  For each \nparticipant,  only the first occurrence  of the case for each endpoint  category  is counted  for the analysis;  N=Number  of participants  randomized  and dosed  with clesrovimab  or placebo;  n=Number  of \nparticipants  eligible  for inclusion  in the full analysis  set population;  Abbreviations:  CI=Confidence  Interval;  LRI=Lower  Respiratory  Tract  Infection;  MALRI=Medically -Attended  Lower  Respiratory  \nTract  Infection.\nConfidentialConfidential\nProtocol  004:  Safety\nWell-tolerated  in healthy  preterm  and full-term infants  with a safety  profile  that is generally  comparable  to placebo\n11Participants  with AEsClesrovimab \nNa = 2,409Placebo \nNa = 1,202\nn (%) n (%)\nOverall  Solicited and Unsolicited  AEs (Days  1-365 postdose)\n≥ 1 AE 1,816  (75.4) 918 (76.4)\nDrug -related  AE 587 (24.4) 296 (24.6)\nAny SAE 278 (11.5) 149 (12.4)\nDrug -related  SAEb 1 (0.0) 1 (0.1)\nDeathc 7 (0.3) 3 (0.2)\nSolicited  AEs (Days  1-5 postdose)\nInjection  site pain 122 (5.1) 77 (6.4)\nInjection  site erythema 90 (3.7) 40 (3.3)\nInjection  site swelling 65 (2.7) 31 (2.6)\nIrritability 450 (18.7) 237 (19.7)\nSomnolence 303 (12.6) 171 (14.2)\nDecreased  appetite 106 (4.4) 61 (5.1)\nSolicited  Temperature  (Days 1 -5 postdose)\nTemp  < 100.4  °F 2,319  (96.3) 1,154 (96.0)\nTemp  ≥ 100.4  °F 89 (3.7) 48 (4.0)\nAESI  (Days 1 -42 postdose)\nRashd 11 (0.5) 4 (0.3)\nAnaphylaxis/hypersensitivity 1 (0.0)e 0 (0.0)•Proportion  of participants  with AEs, including  solicited  AEs, drug- \nrelated  AEs, and SAEs,  were  generally  comparable  between \nintervention  groups;  majority  of AEs were  Grade  1 or 2 toxicity\n•Most  (≥ 96%)  participants  in either  intervention  group  had a \nmaximum  temperature  <100.4 °F\n•There  were  no serious  AESI  of rash,  anaphylaxis  or hypersensitivity \nobserved  in either  intervention  group\n•Proportion  of participants  with AESI  in the category  of rash \n(all non-serious)  was low in either  intervention  group\n•One participante experienced  a non-serious  AESI  in the \ncategory  of anaphylaxis/hypersensitivity,  which  was a Grade \n2 event  of bronchospasm  on Day 3 postdose  in clesrovimab \ngroup,  not considered  related  to study  intervention  by \ninvestigator\n•No deaths  were  considered  related  to study  intervention  by \ninvestigator;  no pattern  identified  with respect  to cause  of death \nor timing;  largely  attributable  to underlying  co-morbidities\nNotes:  a. N = number  of participants randomized  and dosed  and included  in the safety  population;  b. One infant  had an SAE of body  temperature  increased  in the clesrovimab  group  (with  rectal  temperature  38°C \non Day 4 and with adenovirus  detected  in stool  on Day 8) and one  infant  had an SAE of B-cell lymphoma  in the placebo  group;  c. One death  occurred  in the clesrovimab group  on Day 487 after study  discontinuation \n(discontinued  study  based  on physician’s  recommendation);  d. All AESI  of rash were  non-serious;  All events  were  Grade  1 or 2 toxicity  except  for one Grade  3 event  of urticaria  on Day 9 postdose  in clesrovimab  \ngroup,  not considered  related  to study  intervention  by investigator.  Abbreviations : AE=Adverse  Event;  AESI=Adverse  Events  of Special  Interest;  SAE=Serious  Adverse  Event.\nConfidential\nProtocol  004:  Conclusions\n12Efficacy\n̶ Clesrovimab,  administered  as a single  \ndose for infants  of all weights,  provides  \nrobust protection  against  mild,  \nmoderate,  and severe  RSV disease  for \nall healthy  infants, including  term and \npreterm\n̶ Clinical  data demonstrate  over 90% efficacy \nin preventing  RSV LRI hospitalizations \nthrough  6 months\n̶ Clesrovimab  efficacy  is durable  across  \nall efficacy  endpoints  through  6 months\n̶ There  was no shifting  of RSV  disease  \nburden seen  in the second  RSV season\nSafety\n̶ Clesrovimab  is well tolerated  in healthy \npreterm  and full-term  infants  born during  or \nentering  their first RSV season, with a safety \nprofile  that is generally  comparable  to placebo\nAbbreviations:  LRI=Lower  Respiratory  Tract  Infection;  MALRI=Medically -Attended  Lower  Respiratory  Tract  Infection;  RSV=Respiratory  Syncytial  Virus.\nProtocol  007:\nA Phase  3, Multicenter,  Randomized,  Partially  Blinded, \nPalivizumab - Controlled  Study  to Evaluate  the Safety,  Efficacy, \nand Pharmacokinetics  of Clesrovimab  in Infants  and Children  at \nIncreased  Risk for Severe  RSV Disease\nConfidential\nProtocol  007: Study  Design\n14•Safety  / Tolerability  – AEs up to day 42 and for 14 days after each \nsubsequent  dose  and SAEs  for duration  of study  (primary)\n•First  RSV Season  PK - Through  8 months\nPalivizumab\n3-5 doses  IM\n(N = 450)\nClesrovimab\n105 mg IM dose  [Day 1]\nPlacebo  [Day 28]\n(N = 446)\nRandomization \n1:1\n(N = 896)aRSV-Associated  Efficacy\n•MALRIb ≥ 1 Indicator  of \nLRI/Severity  (secondary)\n•Hospitalization  (secondary)\n•Severe  MALRI  (tertiary  / \nexploratory)\n•MALRI  ≥ 2 Indicators  of \nLRI/Severity  (post -hoc)Experimental  Arm\nComparator  ArmFirst  RSV \nSeason\nSecond \nRSV\nSeason(N = ~300)\nOpen -label\nClesrovimab\n210 mg\nTo start  9 – 12 months  \nfollowing  participants’  \nfirst RSV season  Dose  1\nNotes:  a. N=Number  of randomized infants,  dosed  with clesrovimab  or palivizumab;  b. MALRI  is defined  as the presence  of the following in  a clinical  setting:  1) cough  or difficulty  breathing;  AND 2) 1 or more   \nof wheezing,  chest  wall in-drawing/retraction,  rales/crackles,  hypoxemia,  tachypnea,  or dehydration;  AND 3) RSV-positive  reverse  transcriptase  polymerase  chain  reaction  (RT-PCR)  nasopharyngeal  sample; \nAbbreviations:  AE=Adverse  Event;  IM=Intramuscular;  MALRI=Medically -Attended  Lower  Respiratory  Tract  Infection;  PK=Pharmacokinetics;  RSV=Respiratory  Syncytial  Virus;  SAE=Serious  Adverse  Event.Protocol  007 study  is \nongoing  and data \nfrom  the second  RSV \nseason  to be reported \nin the futureRSV-Associated  Efficacy\n•MALRI  ≥ 1 Indicator  of \nLRI/Severity  (tertiary  / \nexploratory)\n•Hospitalization  (tertiary  / \nexploratory)\n•MALRI  ≥ 2 Indicators  of \nLRI/Severity  (post -hoc)At Month  5 At Month  6\nPhase  3, multicenter,  randomized,  partially  blinded,  palivizumab -controlled  trial conducted  with active  surveillance over 2 RSV \nseasons\nObjective:  Safety,  pharmacokinetics  and RSV-associated  endpoint  incidence  rates of clesrovimab  in infants  & \nchildren  at increased  risk for severe  RSV disease\nConfidential\nProtocol  007: Baseline  Characteristics\n15Participant  Characteristics  `(`A`ll`D``o`sed Participants  – First RSV Season) Clesrovimab \nN = 446Palivizumab \nN = 450\nParticipants  in Population n (%) n (%)\nParticipants  with Condition\nCLD 124 (27.8) 126 (28.0)\nCHD 52 (11.7) 49 (10.9)\nNeither  CLD nor CHD less than 29 weeks  gestational  agea 26 (5.8) 24 (5.3)\nNeither  CLD nor CHD greater  than or  equal  to 29 weeks  gestational  agea 244 (54.7) 251 (55.8)\nAge at Randomization  (Months)\n<6 409 (91.7) 390 (86.2)\n≥6 to <9 33 (7.4) 51 (11.3)\n≥9 4 (0.9) 9 (2.0)\nMean  (SD) 3.0 (1.9) 3.0 (2.3)\nBody  Weight  at Randomization  (kg)\nMean  (SD) 3.8 (1.5) 3.6 (1.5)\nMedian  (Range)3.5\n(1.1 to 9.6)3.2\n(1.5 to 9.1)\nRace\nAmerican  Indian  Or Alaska  Native 5 (1.1) 7 (1.6)\nAsian 82 (18.4) 80 (17.8)\nBlack  Or African  American 67 (15.0) 71 (15.8)\nMultiple 56 (12.6) 53 (11.8)\nNative  Hawaiian  Or Other  Pacific  Islander 5 (1.1) 2 (0.4)\nWhite 231 (51.8) 237 (52.7)\nEthnicity\nHispanic  Or Latino 138 (30.9) 146 (32.4)\nNot Hispanic  Or Latino 296 (66.4) 296 (65.8)\nNot Reported  or Unknown 12 (2.7) 8 (1.8)\nSex\nMale 225 (50.4) 221 (49.1)\nFemale 221 (49.6) 229 (50.9)\nNotes:  a. Range  of gestational  age was 23 to 41 weeks;  Abbreviations : AAP=American  Academy  of Pediatrics;  CHD=Congenital  Heart  Disease;  CLD=Chronic  Lung Disease;  GA=Gestational  Age; RSV=Respiratory  Syncytial  Virus; \nSD=Standard  Deviation;  Source:  1. Pediatrics.  2014 Aug 1;134(2):e620-38.•Baseline  characteristics \nwere  similar  in both \nclesrovimab and \npalivizumab  arms\n•Enrolled  diverse population \nof different  races  and \nethnicities  from  27\ncountries,  across  6 \ncontinents\n•In total,  401 of 896\n(44.8%)  participants  met \nthe American  Academy  of \nPediatrics  (AAP) \npalivizumab  eligibility \ncriteria  (101 CHD;  250 CLD;\n50 <29 weeks  GA)1\nConfidential\nProtocol  007: Safety\nWell-tolerated  in infants  at increased  risk of severe  RSV disease  with a safety  profile  that is generally  comparable  to \npalivizumab  \n16Participants  with AEsClesrovimab \nNa = 445Palivizumab \nNa = 450\nn (%) n (%)\nOverall  Solicited and Unsolicited  AEs (following  any dose,  first RSV season)\n≥ 1 AE 323 (72.6) 344 (76.4)\nDrug -related  AE 120 (27.0) 127 (28.2)\nAny SAE 99 (22.2) 110 (24.4)\nDrug -related  SAE 0 (0.0) 2 (0.4)\nDeath 8 (1.8) 4 (0.9)\nSolicited  AEs (days 1 -5 postdose,  first RSV season)\nInjection  site pain 26 (5.8) 32 (7.1)\nInjection  site erythema 29 (6.5) 20 (4.4)\nInjection  site swelling 26 (5.8) 12 (2.7)\nIrritability 116 (26.1) 125 (27.8)\nSomnolence 74 (16.6) 72 (16.0)\nDecreased  appetite 52 (11.7) 49 (10.9)\nSolicited  Temperature  (days  1-5 postdose  1, first RSV season)\nTemp  < 100.4  °F 436 (98.0) 441 (98.0)\nTemp  ≥ 100.4  °F 9 (2.0) 9 (2.0)\nAESI  (days 1 -42 postdose  1, first RSV season)\nRash 3 (0.7) 1 (0.2)\nAnaphylaxis/hypersensitivity 0 (0.0) 0 (0.0)•Proportion  of participants  with AEs, including  solicited \nAEs, drug -related  AEs, and SAEs,  were  generally \ncomparable  between  intervention  groups;  majority  of \nAEs were  Grade  1 or 2 toxicity\n•Most  (≥ 98%)  participants  in either  intervention  group \nhad a maximum  temperature  postdose  1 <100.4  °F\n•No AESI  of anaphylaxis/hypersensitivity  were  reported, \nand the proportion  of participants  with AESI  of rash \nwas low in either  intervention  group; all events  were \nnon-serious  and Grade  1 toxicity\n•No deaths  were  considered  related  to study \nintervention  by investigator;  no pattern  identified  with \nrespect  to cause  of death  or timing;  largely  attributable \nto underlying  co-morbidities\nNotes:  a. N = Number  of participants  randomized  and dosed  and included  in the safety  population;  Abbreviations: AE=Adverse  Event;  AESI=Adverse  Event  of Special  Interest;  SAE=Serious  Adverse  Event.\nConfidential\nProtocol  007: Incidence  Rates\nComparable  RSV disease  incidence  between  clesrovimab  and palivizumab  groups\n17RSV-Associated  Endpointa\n(Through  5 months  Postdose)Clesrovimab \n(N = 446)Palivizumab \n(N = 450)\nnNumber  of \nEventsIncidence  Rate,  % \n(95% CI)d nNumber  of \nEventsIncidence  Rate,  % \n(95% CI)d\nMALRI  Requiring  ≥ 1 \nIndicator  of LRI/Severityb 443 143.6\n(2.0, 6.0)437 123.0\n(1.6, 5.3)\nHospitalizationc 443 51.3\n(0.4,  3.0)437 61.5\n(0.6,  3.3)\nNotes : a. MALRI  includes  both inpatient  and outpatient  cases;  b. Defined  as: RSV PCR positive  and cough  or difficulty  breathing  and at least  1 of the following:  wheezing,  chest  wall indrawing/retractions,  \nrales/crackles,  hypoxemia,  tachypnea,  or dehydration  due to respiratory  symptoms;  c. Respiratory  Infection  Hospitalization  defined  as: RSV PCR positive  and hospital  admission  for respiratory  illness;  d. \nConfidence  intervals  were  estimated  by exact  Poisson  confidence  limits;  N=number  of participants  randomized  and dosed  with clesrovimab  or palivizumab;  n=number  of participants eligible  for inclusion  in \nthe full analysis  set population;  Abbreviations : CI=Confidence  Interval;  LRI=Lower  Respiratory  Tract  Infection;  MALRI=Medically -Attended  Lower  Respiratory  Tract  Infection.Note:  Incidence  rates  in Protocol  007 are similar through  6 months  postdose\nConfidential\nProtocol  007: PK Bridging\nSupports  extrapolation  of efficacy  to infants  with increased risk of severe RSV with no dose-adjustment  necessary\n18•Non-inferiority  trial in infants  with increased risk of \nsevere  RSV would  be infeasible  due to prohibitively \nlarge  sample  size in already  small  population\n•In agreement  with regulators,  PK bridging  along \nwith evaluation  of estimation  of efficacy  in Protocol \n007 was deemed  acceptable  for assessment  of \nefficacy  in this population\n•PK exposures  in infants  with increased  risk for severe \nRSV are similar  to those  found  in healthy  infants , \nsupporting  extrapolation  of efficacy  to population\nof preterm  birth,  CLD and/or  CHD infants , without \nrequiring  dose  adjustmentsReference  Group\nAbbreviations : AUC=Area Under  the Curve;  CHD=Congenital  Heart Disease;  CLD=Chronic  Lung  Disease;  PK=Pharmacokinetics;  RSV=Respiratory  Syncytial  Virus.PK exposures  in infants  at increased  risk of severe  RSV \nare similar  to those  in healthy  infants\nConfidential\nProtocol  007: Conclusions\n19Efficacy\n̶ Efficacy  in Protocol  007 population  was \ninferred  by efficacy  established  from \nProtocol  004, based  on comparable \nclesrovimab  pharmacokinetic  data\n̶ In infants  at increased  risk for severe  RSV \ndisease,  a single  dose of clesrovimab \nprotects  against  RSV disease , including  RSV \nhospitalization,  through  6 months\nSafety\n̶ The safety  profile of clesrovimab  in infants  at \nincreased  risk of severe  RSV disease  is \ngenerally comparable  to palivizumab  and \nconsistent  with the  safety  profile  in healthy  \ninfants\nAbbreviations : RSV=Respiratory  Syncytial  Virus.\nSummary\nConfidential\nClesrovimab  Phase  2b/3 Study  Conclusions\n21Efficacy\nClesrovimab,  administered  as a single  dose  for \ninfants  of any weight,  provides  robust  protection \nagainst  mild,  moderate,  and severe  RSV disease \nfor all infants,  including  term,  preterm,  and those \nwith risk factors\n✓In healthy  infants,  clesrovimab  is highly  efficacious \nagainst  a broad  spectrum  of RSV disease  endpoints, \nwith no shifting  of RSV disease  burden  in second  RSV \nseason  (Protocol  004)\n✓Over  90% efficacy  in preventing  RSV LRI \nhospitalizations  through  6 months\n✓Clesrovimab  also protects  infants  at increased  risk \nfor severe  RSV disease , comparable  to palivizumab  \n(Protocol  007)\n✓The dose  is same  for infants  of all weights\n✓Efficacy  is sustained  through  6 months,  providing  \ndurable  efficacy  for an entire  typical  RSV season\nSafety\nClesrovimab  is well-tolerated  in infants,  with a \nsafety  profile  that is generally  comparable  to \ncontrols  and consistent  across  infant \npopulations.\n̶ Clesrovimab  is well tolerated  in healthy  preterm \nand full-term  infants  born during  or entering  their \nfirst RSV  season, with a safety  profile  that is \ngenerally  comparable  to placebo\n̶ The safety  profile  of clesrovimab  in infants  at \nincreased  risk for severe  RSV disease  is generally \ncomparable  to palivizumab  and consistent  with the \nsafety  profile  in healthy  infants\nAbbreviations : LRI=Lower  Respiratory  Tract  Infection;  MALRI=Medically -Attended  Lower  Respiratory  Tract  Infection;  RSV=Respiratory  Syncytial  Virus.\nThank  you", "summary": "Clesrovimab  (MK-1654):  Pediatric  Clinical  Program Presentation  to the Advisory  Committee  on Immunization  Practices Anushua  Sinha,  MD, MPH Clinical  Director  -Vaccines  Clinical  Research  Merck  & Co., Inc. Rahway,  NJ, USA October  23, 2024 Confidential Clesrovimab  is a human  monoclonal  antibody  with four unique  molecular  characteristics  that enable  robust  and durable  protection  from  RSV 2Notes: a. Clesrovimab  is ~50-fold more  potent  in vitro than palivizumab; …", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-23-24-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/02-RSV-Mat-Peds-Sinha-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 22}
{"title": "03 RSV Mat Peds DeSilva 508", "content": "RSVpreF Vaccine, Preterm Birth, and \nSmall for Gestational Age at Birth \nPreliminary Results from \nThe Vaccine Safety Datalink\nMalini DeSilva, MD, MPH\nACIP\nOctober 23, 20241\n\nVaccine Safety Datalink, 2024\n•Collaborative project between \nCDC and 13 integrated \nhealthcare organizations\n•Monitors safety of vaccines \nused in the U.S., primarily \nthrough observational \nmultisite studies of rare and \nserious events following \nvaccination\n•Includes data on ~15.5 million \nindividuals across all sites \nannually (~3 -4% of U.S. \npopulation)\n•Annual birth Cohort ~ 115,000\n•Data is organized using a \ncommon data dictionary with \nstandardized coding systems\nPrenatal RSV \nVaccine \n2023 –2024 season\n•ACIP recommendation 9/22/23:\n•32–36 weeks gestation\n•Seasonal administration \nSeptember – January\n•Most VSD sites did not start \nvaccinating until late October or \nNovember 2023\n•One VSD site did not administer \nvaccine in health system\n•Two VSD sites continued \nadministrations through \n2/29/24\n3\nEvaluation of Preterm Birth and SGA at Birth \nfollowing prenatal RSV vaccine \n•Perform a matched analysis comparing pregnant persons \nexposed to RSV vaccine with pregnant persons unexposed at the \nsame gestational week to evaluate \n•Preterm birth (<37 weeks gestation) \n•Small for gestational age (SGA) at birth (<10th percentile)\n4\nPreterm birth\n•Definition: live birth occurring prior to 37 weeks gestational age\n•RSVpreF  clinical trial identified an imbalance in preterm births in \nvaccinated group compared to placebo group1\n•Most were late preterm (34 –<37 weeks)\n•Most occurred >30 days after vaccination \n•Most prominent in a single country \n•GSK RSV prenatal vaccine clinical trial halted due to imbalance in \npreterm birth in vaccinated2\n51Kampmann B, Madhi  SA, Munjal I, et al. Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants. \nN Engl J Med. 2023 Apr 20;388(16):1451 -1464. doi: 10.1056/NEJMoa2216480. Epub  2023 Apr 5. PMID: 37018474.\n2Dieussaert I, Hyung Kim J, Luik S, et al. RSV Prefusion F Protein -Based Maternal Vaccine - Preterm Birth and Other \nOutcomes. N Engl J Med. 2024 Mar 14;390(11):1009 -1021. doi: 10.1056/NEJMoa2305478. PMID: 38477988.\nSmall for Gestational Age (SGA) at birth\n•Definition: Birthweight below 10% for gestational age and sex\n•Causes\n•Constitutionally small – parental genetics\n•Intrauterine growth restriction (IUGR) – \n•Placentation issues → decreased placental blood flow  \n•Maternal conditions (chronic heart or lung disease, HTN, CKD, DM, \ninfection, cigarette use, alcohol or drug use, malnutrition, infections)\n•Genetic or structural abnormalities\n•Early onset IUGR <32 weeks gestational age usually more severe \nwith higher morbidity/mortality\n•SGA at birth not evaluated in clinical trial, but imbalance in low \nbirth weight (≤2500g) among RSVpreF  vaccinated\n6\nMatched analysis methods\n•Pregnant persons 16 –49 years with gestational age 30 –<37 weeks \nduring 9/22/2023 –1/31/24 (2/29/24 for two sites)\n•Target trial emulation design to compare vaccinated and \nunvaccinated persons at each gestational week\n•Pregnant persons exposed to RSVpreF  vaccine matched 1:1 on VSD site and \npropensity to be vaccinated to unvaccinated pregnant persons during same \ngestational week\n•Unvaccinated index date = gestational day of vaccine\n•Matched pair censored if unvaccinated person later vaccinated\n•Propensity to be vaccinated calculated individually for 2 sites and for \nall other sites combined\n•Maternal age at pregnancy start, calendar week at pregnancy start, number of \nweeks with prenatal care encounters, race/ethnicity, comorbidities \n(hypertension, diabetes mellitus, gestational hypertension, gestational \ndiabetes, obesity, substance use), history of preterm labor, poor fetal growth, \nsupervision of high -risk pregnancy, enrollment, and VSD site\n7\nAnalysis\n•For SGA at birth, matched sets excluded if infant weight not \navailable for either infant in matched pair\n•Log binomial model with robust variance to estimate risk \nratios with 95% confidence intervals\n•Overall (30 –<37 weeks gestational age)\n•Restricted to vaccines administered during 32 –<37 weeks \ngestational age (ACIP recommendation)\n8\nMatched Cohort* characteristics, N = 14,099\n9Age groupRSV Vaccinated, \nn(%)Unvaccinated match,\nn(%)\n•16–24 years 1418 (10.1) 1607 (11.4)\n•25–29 years 3180 (22.6) 3471 (24.6)\n•30–34 years 5514 (39.1) 5325 (37.8)\n•35–39 years 3320 (23.5) 3050 (21.6)\n•40–49 years 667 (4.7) 646 (4.6)\nRace/Ethnicity\n•Asian 3061 (21.7) 2651 (18.8)\n•Black 873 (6.2) 1007 (7.1)\n•Hispanic 4488 (31.8) 4730 (33.5)\n•White 4604 (32.7) 4595 (32.6)\n•Other/Unknown 1073 (7.6) 1116 (7.9)\n*Not unique individuals due to crossover from unvaccinated to vaccinated\nPreterm birtha risk among pregnant persons receiving RSV \nvaccine and unvaccinated matches, 30 –36 weeks GA\nMatched \npairs, NRSV vaccinated Unvaccinated matchRisk Ratio \n(95% CI)\nN events*Preterm \nbirth %N events*Preterm \nbirth %\nOverallb14,099 571 4.0 637 4.50.90 \n(0.80 –1.00)\n32–36 \nweeks13,965 563 4.0 628 4.50.90 \n(0.80 –1.00)\n10GA = gestational age\naPreterm  birth = birth <37 weeks gestational age\nbN RSV vaccines administered <32 weeks = 134 (0.95%)\n*Events only included through date of censoring when unvaccinated pair crosses over to vaccinated\nPreterm birth risk by GA* at vaccination or index \ndate for matched sets 32 –36 weeks GA*\n11\nSmoothed curve showing average preterm birth risk (line) by gestational age at vaccination or \nindex date with 95% confidence band (shading)\n*GA = gestational age\nMatched \npairs, NRSV vaccinated Unvaccinated matchRisk Ratio \n(95% CI)\nN \nevents*SGA at \nbirth %N \nevents*SGA at birth \n%\nOverall 11,920 800 6.7 781 6.61.02 \n(0.93 –1.13)\n32–36 \nweeks11,819 799 6.8 774 6.51.03 \n(0.94 –1.14)\n12SGAa at birth risk in infants born to RSV vaccinated pregnant \nperson or unvaccinated pregnant matches, 30 –36 weeks GAb \naSGA  at birth = “Small for Gestational Age”; birthweight <10th percentile for gestational age compared \nwith a U.S. reference population1\nbGA = gestational age\n*Events only included through date of censoring when unvaccinated pair crosses over to vaccinated \n Note: 11,920 matched pairs with complete infant weight data (85%)\n1Talge NM, Mudd LM, Sikorskii  A, Basso O. United States birth weight reference corrected for \nimplausible gestational age estimates. Pediatrics 2014;133:84453. PMID:24777216\nConclusions and next steps\n•RSVpreF  vaccine is not associated with increased risk for preterm \nbirth or SGA at birth\n•Currently working on analysis for acute safety outcomes, \nstillbirth, and preeclampsia/eclampsia/HELLP\n•Chart review for stillbirths and some acute safety outcomes (i.e., \nanaphylaxis, Guillain -Barré syndrome, acute disseminated \nencephalomyelitis, transverse myelitis, venous \nthromboembolism, pulmonary embolism, and \nmyocarditis/pericarditis)\n•Preeclampsia/eclampsia/HELLP – association with hypertensive \ndisorders of pregnancy in recent study1 and clinical trial\n131Son M, Riley LE, Staniczenko AP , et al. Nonadjuvanted Bivalent Respiratory Syncytial Virus Vaccination and Perinatal \nOutcomes. JAMA Netw  Open. 2024;7(7):e2419268. doi:10.1001/jamanetworkopen.2024.19268\nOur Team\nHealthPartners\n•Malini DeSilva\n•Elyse Kharbanda\n•Jacob Haapala\n•Gabriela Vazquez -Benitez\n•Leslie Kuckler\n•Jingyi Zhu\n•Sunita Thapa\n•Nicole Trower\n14Weill Cornell Medicine\n•Heather Lipkind\nKaiser  Northwest\n•Kimberly Vesco\nCDC\n•Eric Weintraub\n•Elizabeth QuincerOther VSD sites\n•Acumen\n•Denver Health\n•Harvard Pilgrim\n•Indiana University\n•Kaiser Permanente Northwest\n•Kaiser Permanente Colorado\n•Kaiser Permanente Southern \nCalifornia\n•Kaiser Permanente Northern \nCalifornia\n•Kaiser Permanente Washington\n•Kaiser Permanente Mid -Atlantic \nStates\n•Marshfield Clinic\n•OCHIN", "summary": "RSVpreF Vaccine, Preterm Birth, and  Small for Gestational Age at Birth  Preliminary Results from  The Vaccine Safety Datalink Malini DeSilva, MD, MPH ACIP October 23, 20241  Vaccine Safety Datalink, 2024 •Collaborative project between  CDC and 13 integrated  healthcare organizations •Monitors safety of vaccines  used in the U.S., primarily  through observational  multisite studies of rare and  serious events following  vaccination •Includes data on ~15.5 million  individuals across all sites …", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-23-24-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/03-RSV-Mat-Peds-DeSilva-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 14}
{"title": "04 RSV Mat Peds Moulia 508", "content": "Maternal & Pediatric RSV Work Group Interpretations \nand Next Steps\nDanielle Moulia, MPH \nCo-Lead, Maternal/Pediatric RSV Work Group  \nACIP Meeting\nOctober 23, 2024 \n1U.S. Centers for Disease Control and Prevention\n\nSafety and efficacy of clesrovimab\n2\nPolicy question being considered by the work group\n•Should clesrovimab  be recommended for all infants <8 months of age \nentering their first RSV season  or born during the RSV season?\n3\nEvidence reviewed by the work group\n•Safety and efficacy of clesrovimab\n-Phase 2b/3 placebo -controlled study in healthy preterm infants (≥29 \nto <35 weeks gestational age) and full -term infants (≥35 weeks \ngestational age)\n-Phase 3 palivizumab -controlled study in infants at increased risk for \nsevere RSV disease\n4\nWork group interpretation of clesrovimab  efficacy \ndata\n•Phase 2b/3 trial demonstrated high efficacy for prevention of severe RSV \ndisease through 150 days \n*Defined by the presence of the following: cough or difficulty breathing; AND ≥ 1 indicator of LRI (lower respiratory infecti on)  or severity (wheezing, chest wall in -\ndrawing/retractions, rales/crackles, hypoxemia, tachypnea, dehydration due to respiratory symptoms ); AND hospital admission for respiratory illness; AND RSV \npositive reverse transcriptase -polymerase chain reaction (RT -PCR) nasopharyngeal (NP) sample. \n**Defined by the presence of the following seen in an outpatient or inpatient clinical setting: cough or difficulty breathing  and ≥ 1 indicator of (lower respiratory \ninfection) or severity (wheezing, chest wall in -drawing/retractions, rales/crackles, hypoxemia, tachypnea, dehydration due to respiratory s ymptoms); and RSV positive \nreverse transcriptase -polymerase chain reaction (RT -PCR) nasopharyngeal (NP) sample. \n5Outcome n/N, clesrovimab n/N, placebo Efficacy % (95% CI)\nHospitalization for RSV-\nassociated lower respiratory \ntract infection*5/2,398 27/1,201 90.9 (76.2, 96.5)\nMedically -attended  RSV-\nassociated lower respiratory \ntract infection ≥ 1 indicator of \nlower respiratory infection or \nseverity**60/2,398 74/1,201 60.4 (44.1, 71.9)\nMerck, presented at IDWeek  in Los Angeles, California from October 16 -19, 2024\nWork group interpretation of clesrovimab  safety data \n•Serious adverse events appeared balanced between the clesrovimab  and \nplacebo arms, however rare adverse events are unlikely to be detected in a \ntrial of this size \n•Solicited adverse events were balanced between the clesrovimab  and \nplacebo arms\n-In both arms, irritability and sleepiness was the most commonly observed \nsolicited adverse event\n6 Merck, presented at IDWeek  in Los Angeles, California from October 16 -19, 2024\nWork group considerations regarding clesrovimab\n•Initial efficacy and safety data look promising; however, the work group has \nrequested additional pharmacokinetic, efficacy, and safety data from the \nmanufacturer  \n•Work group discussion also highlighted:\n-Clesrovimab  has demonstrated a shorter half -life than nirsevimab  (421 vs 712 days), however \nefficacy against severe RSV appeared sustained at 150 and 180 days\n-Trial enrollment began in 2021, a period when typical RSV seasonality had been disrupted by the \nCOVID -19 pandemic\n-Clesrovimab  and nirsevimab  trial outcomes had different definitions\n•Overall, the work group felt that the initial data merited moving forward \nwith the evidence review for the policy question \n1 Maas et al. https://www.sciensano.be/sites/default/files/pk_sna_and_efficacy_against_rsv_malri_from_a_phase_1b2a_study_of_the_monoclonal_ antibody_clesrovimab_mk -\n1654_in_infants.pdf   2. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761328s000lbl.pdf 7\nEvidence to be reviewed by the work group \n•Additional data on Phase 2b/3 and Phase 3 studies requested by work \ngroup\n•GRADE of evidence\n•Cost effectiveness analysis\n•Evidence to Recommendation Framework ( EtR)\n-Public health problem\n-Benefits and harms\n-Values\n-Acceptability\n8-Feasibility\n-Resource use\n-Equity\nProposed timeline\n•February 2025\n-Summary of GRADE\n-Evidence to Recommendation Framework\n-Cost effectiveness analysis \n•ACIP vote timing dependent on FDA licensure\n9\nMaternal RSV vaccine safety\n10\nImbalance of preterm birth was observed in clinical \ntrials for the Pfizer maternal RSV vaccine ( Abrysvo ) \n•In clinical trials, maternal RSV vaccine was administered at 24 –36 weeks' gestation, \nand more preterm births and hypertensive disorders of pregnancy were observed \namong pregnant people who received maternal RSV vaccine ( Abrysvo )vs. placebo, \nbut the differences were not statistically significant\n– Data were insufficient to establish or exclude a causal relationship\n•FDA approved maternal RSV vaccine ( Abrysvo ) for use in pregnant persons at 32 –36 \nweeks’ gestation to avoid the potential risk for preterm birth at <32 weeks’ gestation \n•ACIP judged the benefits of maternal RSV vaccine ( Abrysvo ) at 32 –36 weeks’ \ngestation to outweigh the potential risks for preterm birth and hypertensive \ndisorders of pregnancy\n11\nMaternal RSV vaccine safety: first season analysis of \npreterm birth and small for gestational age \n•Preliminary findings from the first season of maternal RSV vaccine in a Vaccine Safety Datalink \n(VSD) study found that maternal RSV vaccine during 32 –36 weeks’ gestation was not \nassociated with an increased risk of preterm birth or small for gestational age1\n•The work group felt that these data were very reassuring.\n1. DeSilva, M.  RSVpreF  Vaccine, Preterm Birth, and Small for Gestational Age at Birth Preliminary Results from The Vaccine Safety Datalink. Presented at ACIP October 23, 2024 2. Talge  NM, Mudd LM, Sikorskii  \nA, Basso O. United States birth weight reference corrected for implausible gestational age estimates. Pediatrics 2014;133:844 53. PMID:2477721612Matched \npairs, NRSV vaccinated Unvaccinated matchRisk Ratio (95% \nCI)\nN events* Percent % N events* Percent %\nPreterm birtha13,965 563 4.0 628 4.50.90 \n(0.80 –1.00)\nSmall for gestational ageb11,819 799 6.8 774 6.51.03 \n(0.94 –1.14)\naPreterm  birth = birth <37 weeks gestational age bSGA at birth = “Small for Gestational Age”; birthweight <10th percentile for gestational age compared with a U.S. reference \npopulation2\n*Events only included through date of censoring when unvaccinated pair crosses over to vaccinated\nWork group interpretation of maternal RSV vaccine \nsafety data\n•The work group felt that messaging about potential risks for hypertensive disorder \nof pregnancy should be separated from preterm birth\n•Little post -licensure data available for risk of hypertensive  disorder of pregnancy \n•One study conducted a secondary analysis  of 2,973 pregnant individuals (1,011 \nvaccinated and 1,962 unvaccinated) found an association of maternal RSV vaccine \nand hypertensive disorder of pregnancy1 \n•Some WG members felt that when counseling pregnant people on maternal RSV \nvaccination at 32 –36 weeks, messaging on potential risks of preterm birth could be \nsoftened or counselling no longer needed to include discussion regarding a \npotential risk of preterm birth \n•CDC and FDA should continue to monitor safety data for maternal RSV vaccine, \nincluding further VSD analyses for  hypertensive disorders of pregnancy \n131. Son M, Riley LE, Staniczenko  AP, et al. Nonadjuvanted Bivalent Respiratory Syncytial Virus Vaccination and Perinatal Outcomes. JAMA Netw  Open. 2024;7(7):e2419268. \ndoi:10.1001/jamanetworkopen.2024.19268\n14", "summary": "Maternal & Pediatric RSV Work Group Interpretations  and Next Steps Danielle Moulia, MPH  Co-Lead, Maternal/Pediatric RSV Work Group   ACIP Meeting October 23, 2024  1U.S. Centers for Disease Control and Prevention  Safety and efficacy of clesrovimab 2 Policy question being considered by the work group •Should clesrovimab  be recommended for all infants <8 months of age  entering their first RSV season  or born during the RSV season? 3 Evidence reviewed by the work group •Safety and efficacy…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-23-24-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/04-RSV-Mat-Peds-Moulia-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 14}
{"title": "01 mening Loehr 508", "content": "Introduction to Meningococcal Session\nJamie Loehr, MD\nAdvisory Committee on Immunization Practices\nOctober 24, 2024National Center for Immunization & Respiratory Diseases\n1\n23 Terms of Reference\nGSK pentavalent ( MenABCWY ) vaccine\n–Prescription Drug User Fee Act date for regulatory decision:  \n•February 14, 2025\nMenB- 4C (Bexsero) FDA interval and dosing change\nRevisiting the adolescent meningococcal vaccine schedule \n33 Terms of Reference\nGSK pentavalent ( MenABCWY ) vaccine  Vote Feb 2025\n–Prescription Drug User Fee Act date for regulatory decision:  \n•February 14, 2025\nMenB- 4C (Bexsero) FDA interval and dosing change  Vote Oct 2024\nRevisiting the adolescent meningococcal vaccine schedule Vote 2025\n4GSK Pentavalent ( MenABCWY ) Vaccine\nToday:\n–Cost -effectiveness\n–Evidence to Recommendations Framework ( EtR)\n•Includes GRADE\n5MenB -4C (Bexsero) FDA Interval and Dosing Change\nToday:\n–Abridged Evidence to Recommendations ( EtR) Framework\n•Cost -effectiveness and GRADE not indicated\n–Work Group considerations \n–Vote\n0.000.200.400.600.801.001.201.40\n1996 2000 2005 2010 2015 2020 2023Incidence per 100,000\nYearMeningococcal Disease Incidence –\nUnited States, 1996 –2023*\nAbbreviations: MenACWY  vaccine = quadrivalent (serogroups A, C, W, and Y) meningococcal conjugate vaccine; MenB  vaccine = serogroup B meningococcal vaccine\nSource: 1996– 2023 NNDSS Data. *2023 NNDSS data are preliminary.0.13 cases/100,000 populationMenACWY vaccine1.2 cases/100,000 \npopulation\nMenB  vaccine\n6\n00.020.040.060.080.10.12\n2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023Incidence per 100,000\nYearB C Y W Other\nSource: NNDSS data with additional serogroup data from Active Bacterial Core surveillance (ABCs) and state health departments  \n*2023 data are preliminaryTrends in Meningococcal Disease Incidence by \nSerogroup – United States, 2006 –2023*\n7\nAverage Annual Meningococcal Disease Incidence by \nAge Group and Serogroup―United States, 2012 –2021\nSource: NNDSS data with additional serogroup data from ABCs and state health departments0.000.100.200.300.400.500.600.700.800.901.00\n<1 year 1 year 2-4 years 5-10\nyears11-15\nyears16-20\nyears21-25\nyears26-44\nyears45-64\nyears65-84\nyears85+\nyearsIncidence per 100,000\nAge GroupB ACWY Oth/Unk\n8\nAverage Annual Meningococcal Disease Incidence by \nAge Group and Serogroup―United States, 2022 –2023*\nSource: NNDSS data with additional serogroup data from ABCs and state health departments\n *2023 NNDSS data are preliminary.0.000.100.200.300.400.500.600.700.800.901.00\n<1 year 1 year 2-4 years 5-10\nyears11-15\nyears16-20\nyears21-25\nyears26-44\nyears45-64\nyears65-84\nyears85+\nyearsIncidence per 100,000\nAge GroupB ACWY Oth/Unk\n9\n10ACIP Meningococcal Vaccines Work Group \n ACIP Members on the WG\n Jamie Loehr (Chair)\n Wilbur Chen\n Charlotte Moser\n Ex Officio WG Members\n Margaret Bash (FDA)\n Matthew Clark (IHS)\n Xin-Xing Gu (NIH)\n WG Liaisons and Consultants\n Amra Resic  (AAFP)\n Mary Healy (AAP) \n Barb Fluty (ACHA)\n Karyn Lyons (AIM)\n Paul Cieslak (CSTE)\n Kathy Hsu (IDSA)\n Pamela Doyon -Plourde (NACI)\n Jeff Goad (NFID)\n Jessica Cataldi (PIDS)\n Amy Middleman (SAHM)\n Kathy Poehling (Wake Forest)\n Lynn Bahta (Minnesota Department of Health)\n David Stephens (Emory)\n GRADE/ EtR Support\n Doug Campos -Outcalt (Arizona)\n Rebecca Morgan (Case Western Reserve) CDC Contributors\n Sarah Schillie (DBD/NCIRD) – Meningococcal Lead\n Jennifer Collins (DBD/NCIRD) – Hib Lead\n Lucy McNamara (DBD/NCIRD)\n Avnika Amin (DBD/NCIRD)\n LeAnne Fox (DBD/NCIRD)\n Susan Hariri (DBD/NCIRD)\n Amy Rubis (DBD/NCIRD)\n Jennie Thomas (DBD/NCIRD)\n Noele Nelson (DBD/NCIRD)\n Alison Albert (DBD/NCIRD)\n Shelby Miller (DBD/NCIRD)\n Michelle Hughes (DBD/NCIRD)\n Madhura Vachon (DBD/NCIRD)\n Gabrielle Cooper (DBD/NCIRD)\n Xiaoyu Dong (ISD/NCIRD)\n Andrew Leidner (ISD/NCIRD)\n Ismael Ortega- Sanchez (CORVD/NCIRD)\n Marc Fischer (DIDRI/NCEZID)\n Jonathan Duffy (DHQP/NCEZID)\n Pedro Moro (DHQP/NCEZID)\n Tanya Myers (DHQP/NCEZID) \n Leslie Lee (OD/NCIRD)\n Manisha (Mo) Patel (OD/NCIRD)\n Jessica MacNeil (ACIP Secretariat)\n Hannah Rosenblum (ACIP Secretariat)\n Melinda Wharton (ACIP Secretariat)", "summary": "Introduction to Meningococcal Session Jamie Loehr, MD Advisory Committee on Immunization Practices October 24, 2024National Center for Immunization & Respiratory Diseases 1 23 Terms of Reference GSK pentavalent ( MenABCWY ) vaccine –Prescription Drug User Fee Act date for regulatory decision:   •February 14, 2025 MenB- 4C (Bexsero) FDA interval and dosing change Revisiting the adolescent meningococcal vaccine schedule  33 Terms of Reference GSK pentavalent ( MenABCWY ) vaccine  Vote Feb…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-23-24-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/01-mening-Loehr-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 10}
{"title": "02 Mening Dong 508", "content": "Economic Analyses of GSK MenABCWY  Vaccinations \namong Adolescents in the United States\nXiaoyu Donga, PhD, Andrew J Leidnera, PhD, Sarah F Schilliea, MD, \nLucy Alexandra McNamaraa, PhD\na National Center for Immunization & Respiratory Diseases, CDC\nDisclaimers: The findings and conclusions in this report are those of the authors and do not necessarily represent the \nviews of the Centers for Disease Control and Prevention. National Center for Immunization & Respiratory Diseases\nACIP Meeting\nOctober 24, 2024\n•Authors have no known conflict of interestsConflict of Interest\n2\n•Q=MenACWY  (Quadrivalent)\n•B=MenB\n•P=MenABCWY  (Pentavalent)\n•QALY=Quality -adjusted life year\n•ICER= Incremental cost-effectiveness ratio ($/QALY)\n•IMD=Invasive meningococcal disease\n•VE=Vaccine effectiveness\n•PICO= Population intervention comparator outcomeAcronyms \n3\n•Research Question\n•Methods\n•Model Inputs\n•Results\n•Sensitivity Analyses\n•Comparison to GSK’s Model\n•Limitations\n•SummaryOutline\n4\n•What is the cost -effectiveness of vaccinating adolescents with the GSK \npentavalent vaccine ( MenABCWY ) compared to the current \nrecommendation of MenACWY / MenB  vaccine?Research Question\n5\n•Current Recommendation\n-MenACWY  vaccine (Q): 1st dose at 11 –12 yrs; 2nd dose at 16 yrs.\n-MenB  vaccine (B): 1st and 2nd dose at 16 –23 yrs (preferred 16 –18 yrs),                            \nbased on shared clinical decision -making.\n•Policy Question (PICO): \n-PICO 1: Should the pentavalent vaccine (P , MenABCWY ) be included as an option \nfor MenACWY /MenB  vaccination in people currently recommended to receive \nboth vaccines at the same visit?               Q -P-B\n-PICO 2: Should the pentavalent vaccine be included as an option for people \ncurrently recommended to receive MenACWY  only?              P -P\n-PICO 3: Should the pentavalent vaccine be included as an option for people \ncurrently recommended to receive MenB  only?              Q-P-PaOverview\nQ-QB-B \n6a For PICO 3 in this model, the P -P doses are given at the same coverage rate currently experienced by B -B.\nMethods\n7\nEconomic Analysis\nPICO Interventions Comparators\n1 Q-P-B Q-QB-B \n2 P-P Q-Q\n3 Q-P-P Q-QB-B / Q -P-B\nFor reference Q-P-B / Q -QB-B / P -P /\nQ-Q / Q-P-PNo vaccination\nCostsIntervention  – CostsComparator                                           Change in costs\n   =                                                = $/Outcome\nOutcomesIntervention  – OutcomesComparator                             Change in outcomes\n8Q=Quadrivalent ( MenACWY ) vaccine; B= MenB  vaccine; P=Pentavalent ( MenABCWY ) vaccine.\nModel Diagrama \n9\na Notes: 1/ This figure illustrates any type of vaccine administration at specific ages, for example \"Q dose 1 at 11 years old\"  or \"B dose 2 at 17 years old.\" \n2/ Over time, the portion of the population \"protected by vaccine\" will decrease as vaccine effectiveness wanes, shifting the se individuals to the \"not \nprotected by vaccine\" compartment. 3/ Age -based background mortality rates were applied to all individuals in the model but are not represented in \nthe diagram.\nb Potential sequelae include hearing loss, skin scarring, neurological disabilities, and amputations. See slide 15 for more det ails. \n•Population -based Model\n-Single age cohort, cohort starts at 11 years old (initial population size: 4,068,564 ) \n•Analytic Horizon : \n-Vaccination costs and meningococcal cases are assessed for 19 years (age 11 \nthrough 29)  \n-Costs and health outcomes of meningococcal cases are assessed from age 11 \nthrough the entire lifetime\n•Discount Rate : 3%\n•Currency Year:  2024$US\n•Perspective : Societal\n•Time Step : 0.5 year\n-Outcomes are calculated every 6 months in the modelEconomic Model\n10\n•Inputs\n-Population and Epidemiology\n-Vaccine Characteristics\n-Costs (2024$)\n-Quality of Life Impacts of IMD (Invasive Meningococcal Disease) and Sequalae\n•Outputs\n-Health Outcomes: episodes of IMD, and deaths\n-Costs Outcomes: direct medical costs, productivity costs, and vaccination costs\n-Incremental Cost -effectiveness Ratio (ICER) : $/QALY savedInputs and Outputs\n11IMD=Invasive meningococcal disease; QALY=Quality -adjusted life year.\nModel Inputs\n12\n•Population Size, and Background Mortality Rate By Agea\n•IMD Incidence Rate by Ageb:\n-Serogroups ACWYc:\n•Unvaccinated individuals experience pre -vaccine era incidence (2003 -2005)\n-Serogroup B: \n•Unvaccinated individuals experience pre -vaccine era incidence (2012 -2014)\n•Case Fatality Ratec,d\n•Probability of Sequalae Given IMD EpisodeePopulation and Epidemiological Inputs\na  CDC WONDER                                                                              b Active Bacterial Core Surveillance and NNDSS  data\nc Surveillance data primarily captures serogroup CWY because there is minimal serogroup A disease in the US. \nd Enhanced Meningococcal Disease Surveillance Report 2020 -23     e Ortega -Sanchez IR, ACIP presentation, June 202313IMD=Invasive meningococcal disease.\nIMD Incidence Rates among Unvaccinated by Agea,bPopulation and Epidemiological Inputs \nCase Fatality Ratesb,c\nSerogroup Base Low High\nACWY 15.4% 9.2% 19.4%\nB 9.4% 6.6% 10.9%\na Active Bacterial Core surveillance and NNDSS  data; pre -vaccine era: 2003 -05 for serogroups ACWY, and 2012 -14 for serogroup B.\nb Surveillance data primarily captures serogroup CWY because there is minimal serogroup A disease in the US. \nc  Enhanced Meningococcal Disease Surveillance Report 2020 -23 14\nIMD=Invasive meningococcal disease.\n•Percentage of IMD Cases Developing SequelaeaPopulation and Epidemiological Inputs \nType of Condition Base Low High\nHearing Loss 8.8% 2.0% 20.0%\nSkin Scarring 7.6% 0.00% 19.0%\nNeurologic Disability 2.1% 0.02% 11.0%\nSingle Amputation 1.9% 0.5% 10.0%\nMultiple Amputation 1.2% 0.02% 6.0%\naOrtega -Sanchez IR, ACIP presentation, June 2023\n15IMD=Invasive meningococcal disease.\n•Initial Vaccine Effectiveness (VE) by Serogroupsa and Doses of VaccineVaccine Inputs\nMenACWY (Q) MenB  (B)\n1st Dose79%\n(49% -91%)c64%\n(54% -85%)e\n2nd + Doseb 99%\n(95% -100%)d79%\n(63% -85%)f\n16a The VE for the first dose of MenACWY  is based on observed clinical effectiveness, whereas all other VE values are derived from immunogenicity data.\nb For the Q -P-P strategy, we assume that the last dose of P (i.e., the 3rd dose with serogroup ACWY protection) provides the same initial VE and rate of waning \nfor serogroup ACWY as the 2nd dose MenACWY .\nc Cohn AC et al . Pediatrics. 2017\nd Tipton M et al . Vaccine. 2019; Baxter R et al. Pediatr Infect Dis J. 2014 ; Germán Áñez G et al . Hum Vaccin  Immunother . 2020 .\ne Santolaya  ME et al . Human Vaccines & Immunotherapeutics . 2013 ; Watson PS et al. Expert Review of Vaccines, 2019 ; Castilla et al.  N Engl J Med, 2023\nfWatson PS et al. Expert Review of Vaccines, 2019 ; Vesikari  T et al . Hum Vaccin  Immunother , 2021.  \n•Initial and Duration of Vaccine Effectiveness (VE)  by Serogroups and DosesaVaccine Inputs\n17▪MenACWY  Vaccine (Q) ▪MenB  Vaccine (B)\na Cohn AC et al . Pediatrics. 2017 ; Baxter R et al. Pediatr Infect Dis J. 2014 ; Mbaeyi  SA et al . MMWR Recomm  Rep. 2020 ; Santolaya  ME et al . Human Vaccines & \nImmunotherapeutics . 2013 ; Watson PS et al. Expert Review of Vaccines, 2019 ; Vesikari  T et al . Hum Vaccin  Immunother , 2021.  \n•Vaccination Coverage by Strategy and Vaccine Type (Q, B, P)Vaccine Inputs\nAge at Vaccination\n12y 16.5y 17y\nCurrent Rec: Q -QB-BaQ (88.4%) Q (59.7%) B (32.4%) B (12.8%)\nIntervention: Q -P-B Q (88.4%) Q (27.3%) P (32.4%) B (12.8%)\nQ=Quadrivalent ( MenACWY ) vaccine; B= MenB  vaccine; P=Pentavalent ( MenABCWY ) vaccine .\na National Immunization Survey Data, 2023, https://www.cdc.gov/mmwr/volumes/73/wr/mm7333a1.htm#T1_ down .PICO 1\n18\n•Vaccination Coverage by Strategy and Vaccine Type (Q, B, P)Vaccine Inputs\nAge at Vaccination\n12y 16.5y 17y\nCurrent Rec: Q -QB-BaQ (88.4%) Q (59.7%) B (32.4%) B (12.8%)\nQ-P-B Q (88.4%) Q (27.3%) P (32.4%) B (12.8%)\nIntervention: P -P P (88.4%) P (59.7%)\nQ-Q Q (88.4%) Q (59.7%)PICO 2\n19Q=Quadrivalent ( MenACWY ) vaccine; B= MenB  vaccine; P=Pentavalent ( MenABCWY ) vaccine .\na National Immunization Survey Data, 2023, https://www.cdc.gov/mmwr/volumes/73/wr/mm7333a1.htm#T1_ down .\n•Vaccination Coverage by Strategy and Vaccine Type (Q, B, P)Vaccine Inputs\nAge at Vaccination\n12y 16.5y 17y\nCurrent Rec: Q -QB-BaQ (88.4%) Q (59.7%) B (32.4%) B (12.8%)\nQ-P-B Q (88.4%) Q (27.3%) P (32.4%) B (12.8%)\nP-P P (88.4%) P (59.7%)\nQ-Q Q (88.4%) Q (59.7%)\nIntervention: Q -P-P Q (88.4%) Q (27.3%) P (32.4%) P (12.8%)PICO 3\n20Q=Quadrivalent ( MenACWY ) vaccine; B= MenB  vaccine; P=Pentavalent ( MenABCWY ) vaccine .\na National Immunization Survey Data, 2023, https://www.cdc.gov/mmwr/volumes/73/wr/mm7333a1.htm#T1_ down .\n•Vaccine Cost per Dose (2024$)Vaccine Inputs\nQ (MenACWY ) B (MenB ) P (MenABCWY )Admin Costa\nMenveo MenQuadfi Bexsero Trumenba GSK Vaccineb\nPublicc$109 $111 $150 $136 $181 $34\nPrivatec$168 $184 $243 $206 $241 $34\nMarket Shared50% 50% 75% 25% 100%\nWeighted Cost+ \nAdmin$177 $224 $245\na Tsai Y et al. Preventive Medicine Reports. 2019\nb GSK presentation to the CDC .\nc 2024 public and private sector cost per dose by CDC; the private sector price has been further adjusted by the estimates from  the MarketScan  Claims Database; \nthe percentages of vaccines purchased, and vaccinations administered are assumed to be 50% private sector and 50% public sect or.\nd Market share data are obtained from the MarketScan  Claims Database and Vaccine for Children (VFC) data.\n21\nCost Inputs\nDirect CostaIndirect Costa \n(Productivity Lossb) Base Low High\nIMD $68,544 $31,255 $110,959\nHearing Loss $7,643 $7,039 $11,463 33% Productivitya-c\nSkin Scarring $92,055 $26,918 $116,594\nNeurologic Disability $2,989,564 $1,075,447 $3,631,592 100% Productivitya-c\nSingle Amputation $209,152 $104,575 $313,727 15% Productivityb-d\nMultiple Amputation $250,984 $125,491 $376,474 30% Productivitya-c\nPremature death, 11 -17 $1,750,511\nPremature death, 18 -29 $1,832,198\nIMD=Invasive meningococcal disease.\naOrtega -Sanchez IR, ACIP presentation, June 2023 ; All costs have been converted to 2024 $.\nb Grosse SD et al . J Med Econ. 2019  \nc The productivity loss from an occurrence of permanent sequelae depends  on the age at which the sequelae occurred and the percentage productivity that is \nimpacted by the sequalae.\nd Assumes that a single amputation episode experiences half the productivity loss of a multiple amputation episode. 22\nQALY Inputs: Relative Quality of Life (0 -1 scale) with and \nwithout IMD and Sequelae\nBase Low High Duration\nBackground Utilitya-c0.92 0.89 0.94\nIMD without Sequalaeb\n0.91 0.88 0.946 months\nHearing Lossb0.72 0.64 0.82 Lifetimea,c\nSkin Scarringb0.95 0.80 1.00 Lifetimea,c\nNeurologic Disabilityb0.06 0.00 0.39Lifetimea,c\nSingle Amputationb0.70 0.31 0.80 Lifetimea,c\nMultiple Amputationb0.61 0.31 0.71Lifetimea,c\nDeath 0 0 0\nQALY=Quality -adjusted life year; IMD=Invasive meningococcal disease.\na QALY impacts for sequalae are included in the model as multiplicative weights that are combined with the background utility, so the QALY \nvalue for skin scarring during the years after the IMD episode is equal to 0.874 = 0.95 * 0.92.\nb Ortega -Sanchez IR, ACIP presentation, June 2023\nc Jiang R et al. Qual Life Res. 2021\n23\nResults\n24\nHealth Outcomesa: Cumulative Number of IMD Cases and \nDeaths for a Single Birth Cohort from Ages 11 through 29 Years\na All numbers are cumulative over the analytical horizon of the model for a single cohort of 11 -year -olds. For example, in the “No  Vaccination” strategy, there were a \ntotal of 233 undiscounted episodes of IMD among about 4 million individuals, who started in the model at 11 years old and age d to 29 years old.25PICO 1\nQ=Quadrivalent ( MenACWY ) vaccine; B= MenB  vaccine; P=Pentavalent ( MenABCWY ) vaccine; IMD=Invasive meningococcal disease.\n.\na All numbers are cumulative over the analytical horizon of the model for a single cohort of 11 -year -olds. For example, in the “No  Vaccination” strategy, there were a \ntotal of 233 undiscounted episodes of IMD among about 4 million individuals, who started in the model at 11 years old and age d to 29 years old.26Health Outcomesa: Cumulative Number of IMD Cases and \nDeaths for a Single Birth Cohort from Ages 11 through 29 Years\nQ=Quadrivalent ( MenACWY ) vaccine; B= MenB  vaccine; P=Pentavalent ( MenABCWY ) vaccine; IMD=Invasive meningococcal disease.\n.PICO 2: 12 IMD, 1 Death\na All numbers are cumulative over the analytical horizon of the model for a single cohort of 11 -year -olds. For example, in the “No  Vaccination” strategy, there \nwere a total of 233 undiscounted episodes of IMD among about 4 million individuals, who started in the model at 11 years old and aged to 29 years old.27PICO 3: 1 IMDHealth Outcomesa: Cumulative Number of IMD Cases and \nDeaths for a Single Birth Cohort from Ages 11 through 29 Years\nQ=Quadrivalent ( MenACWY ) vaccine; B= MenB  vaccine; P=Pentavalent ( MenABCWY ) vaccine, IMD=invasive meningococcal disease.\n.\nCost Outcomesa,b: Cumulative Costs for a Single Birth \nCohort from Ages 11 through 29 Years\nDirect Medical Costs\n + Productivity Costs \n($Millions)Vaccination Costs\n($Millions)Total Costs\n($Millions)\nNo Vaccination $93 0 $93\nCurrent Rec: Q -QB-B $52 $1,331 $1,383\nQ-P-B $52 $1,156 $1,208\nP-P $50 $1,360 $1,410\nQ-Q $54 $983 $1,036\nQ-P-P $52 $1,165 $1,217\na Annual discount rate is 3 %.\nb All costs have been converted to 2024$. 28Q=Quadrivalent ( MenACWY ) vaccine; B= MenB  vaccine; P=Pentavalent ( MenABCWY ) vaccine.\nCost -effectiveness of Intervention Strategy vs. \nComparator Strategy for 3 PICO Questions\nQ-QB-B Q-P-B P-P Q-Q Q-P-P\nNo Vaccination $3,572,475 $3,090,247 $3,439,068 $2,697,932 $3,097,938PICO Intervention Comparator Diff. in QALYsaDiff. in CostaICER\n ($/QALY)\n1 Q-P-B Q-QB-B 0 -$175 million Cost -savingb\n2 P-P Q-Q 33 $373 million $11,332,778\n3 Q-P-PQ-QB-B 2 -$166 million Cost -saving\nQ-P-B 2 $9 million $4,510,830\na Annual discount is 3%; 2024$.\nb In this comparison, costs are reduced, but health outcomes remain the same when comparing Q -P-B to Q -QB-B.•Cost per QALY Gained for Each Vaccination Strategy vs. No Vaccination\n29Q=Quadrivalent ( MenACWY ) vaccine; B= MenB  vaccine; P=Pentavalent ( MenABCWY ) vaccine; QALY=Quality -adjusted life year.\nSensitivity Analyses\n30\na This figure presents the six most impactful inputs. Other inputs that were assessed but not included above because they were less impactful: QALYs for each category (background, \nIMD, and sequelae), costs for each category (IMD, sequelae, and death), case fatality ratios for serogroups ACWY and B, rate of skin scarring and multiple amputation from IMD, and \nIMD incidence of serogroups ACWY. At the lower value of P vaccine cost, the ICER was cost -saving, meaning that P -P improves heal th with less costs relative to Q -Q.\nb For the high assumption, we use pre -vaccine era data going back to 1996 to estimate incidence rates among the unvaccinated; for  the lower assumption, we assume that the \nincidence rates are 80% of the base case values.Sensitivity Analysis 1: P -P vs. Q -Qa\n31\nQ=Quadrivalent ( MenACWY ) vaccine; P=Pentavalent ( MenABCWY ) vaccine; IMD=Invasive meningococcal disease; QALY=Quality -adjusted life year.Base Case: $11.3 million/QALY\nCost -savinga\na This figure presents the six most impactful inputs. Other inputs that were assessed but not included above because they were less impactful: QALYs for each category (background, \nIMD, and sequelae), costs for each category (IMD, sequelae, and death), case fatality ratios for serogroups ACWY and B, rate of skin scarring and multiple amputation from IMD, and \nIMD incidence of serogroup B. At the lower value of P vaccine cost, the ICER was cost -saving, meaning that Q -P-P improves health  with less costs relative to Q -P-B.\nb For the high assumption, we use pre -vaccine era data going back to 1996 to estimate incidence rates among the unvaccinated; for  the lower assumption, we assume that the \nincidence rates are 80% of the base case values.Sensitivity Analysis 2: Q -P-P vs. Q -P-Ba\n32\nQ=Quadrivalent ( MenACWY ) vaccine; P=Pentavalent ( MenABCWY ) vaccine; IMD=Invasive meningococcal disease; QALY=Quality -adjusted life year.Cost -savingaBase Case: $4.5 million/QALY\n•Incidence among unvaccinated uses pre-vaccine era data going back to 1996:\n-Serogroups ACWYa: 1996 -2005  (compared to 2003 -05 in the base case)\n-Serogroup B: 1996 -2013  (compared to 2012 -14 in the base case)\n33Sensitivity Analysis 3: Higher IMD Incidence Rate for \nboth MenACWY  and MenB\na Surveillance data primarily captures serogroup CWY because there is minimal serogroup A disease in the US.\n\nQ=Quadrivalent ( MenACWY ) vaccine; P=Pentavalent ( MenABCWY ) vaccine; IMD=Invasive meningococcal disease; QALY=Quality -adjusted life year.\n.Q-QB-B Q-P-B P-P Q-Q Q-P-P\nNo Vaccination $1,522,460 $1,309,296 $1,420,918 $1,140,061 $1,314,758PICO Intervention ComparatorICER ($/QALY)\nHigher IncidenceICER ($/QALY)\nBase Case\n1 Q-P-B Q-QB-B Cost -savingaCost -savinga\n2 P-P Q-Q $3,623,638 $11,332,778\n3 Q-P-PQ-QB-B Cost -saving Cost -saving\nQ-P-B $2,690,624 $4,510,830\na In this comparison, costs are reduced, but health outcomes remain the same when comparing Q -P-B to Q -QB-B.•Cost per QALY Gained for Each Vaccination Strategy vs. No Vaccination•Cost -effectiveness of Intervention Strategy vs. Comparator Strategy for \n3 PICO QuestionsSensitivity Analysis 3: Higher IMD Incidence Rate for \nboth MenACWY  and MenB\n34\nQ-QB-B Q-P-B P-P Q-Q Q-P-P\nNo Vaccination $3,359,810 $2,905,375 $3,020,948 $2,697,932 $2,913,568PICO Intervention ComparatorICER ($/QALY)\nHigher IncidenceICER ($/QALY)\nBase Case\n1 Q-P-B Q-QB-B Cost -savingaCost -savinga\n2 P-P Q-Q $4,369,184 $11,332,778\n3 Q-P-PQ-QB-B Cost -saving Cost -saving\nQ-P-B $4,510,830 $4,510,830\na In this comparison, costs are reduced, but health remains the same when comparing Q -P-B to Q -QB-B. 35Sensitivity Analysis 4: Higher IMD Incidence Rate for \nMenB  among 18 -24 Years Old\n•Cost -effectiveness of Intervention Strategy vs. Comparator Strategy for \n3 PICO Questions\n•Cost per QALY Gained for Each Vaccination Strategy vs. No Vaccination\nQ=Quadrivalent ( MenACWY ) vaccine; P=Pentavalent ( MenABCWY ) vaccine; IMD=Invasive meningococcal disease; QALY=Quality -adjusted life year.\nSensitivity Analysis 5a: Pentavalent Vaccine Price \n36\na Note: 1/ The red arrow and dotted lines in each figure indicate the base case input and results, with the pentavalent vaccine  priced at $211 per dose, resulting in \nICERs of $11 million/QALY and $4.5 million/QALY for each comparison, respectively. 2/ P -P is cost -saving compared to Q -Q when th e vaccine price is below $143. \n3/ Q -P-P is cost -saving compared to Q -P-B when the vaccine price is below $190.Q=Quadrivalent ( MenACWY ) vaccine; B= MenB  vaccine; P=Pentavalent ( MenABCWY ) vaccine.\nCost -saving Cost -savingBase caseBase case\nComparison to GSK’s Model\n37\n•Incidence Rate:\n•Higher in GSKb for MenACWY  and MenB .\n•Coverage Rate:\n•Our model: Based on current coverage rates.\n•GSK: Assumes 89% across vaccines and doses .CDC Model vs. GSK’sa: Differences in Model & Inputs\n38a Note on conflict of interests: GSK manufacturers the GSK MenABCWY  vaccine and the GSK MenB  vaccine.\nb Same as Ortega -Sanchez IR, ACIP presentation, June 2023 , using a longer pre -vaccine era.Q=Quadrivalent ( MenACWY ) vaccine; B= MenB  vaccine; P=Pentavalent ( MenABCWY ) vaccine.\n•Vaccine Effectiveness (VE):\n•Initial VE for 1st dose MenB : 64% (current model) vs. 33.5% ( GSKa).\n•Duration of vaccine protection: \n•In our model, VE declines to 0% in 5 -10 years.\n•In GSK's model, VE declines to 0% after more than 20 years (both vaccines \nmaintain >20% effectiveness at 10 years and ~5% at 20 years).\n•Years of protectionb conferred from MenACWY  vaccination is 6.5 in our model \nand 6.8 in the GSK modelc.\n•Years of protectionb conferred from MenB  vaccination is 3.6 years in our model \nand 6.3 years in the GSK modeld. \n•Sequelae:\n•Current Model: 5 outcomes, aggregate probability per IMD case = 22%.\n•GSKe: 16 outcomes, aggregate probability per IMD case = 55%.CDC Model vs. GSK’s: Differences in Model & Inputs\n39a Argante  et al . BMC Infectious Diseases. 2021  b Years of protection applies to those who were protected following 2 doses .\nc Cohn AC et al . Pediatrics. 2017   d Kuylen et al . Presented at National Immunization Conference, Atlanta GA, 2024\ne Marshall GS et al . Infect Dis Ther . 2024Q=Quadrivalent ( MenACWY ) vaccine; P=Pentavalent ( MenABCWY ) vaccine; IMD=Invasive meningococcal disease.\nCDC Model vs. GSK’s: Differences in Outputs\nPICO Intervention ComparatorICER ($/QALY)\nCDC Model GSK Model\n1 Q-P-B Q-QB-B Cost -savinga Cost -savinga\n2 P-P Q-Q $11.3 million $15.6 million\n3 Q-P-PQ-QB-B Cost -saving Cost -saving\nQ-P-B $4.5 million $1.5 million•Cost -effectiveness of Intervention Strategy vs. Comparator Strategy \nfor 3 PICO Questions\n40a In this comparison, costs are reduced, but health outcome remains the same when comparing Q -P-B to Q -QB-B.Q=Quadrivalent ( MenACWY ) vaccine; P=Pentavalent ( MenABCWY ) vaccine; QALY=Quality -adjusted life year.\n•There are limited VE data, especially for the 2nd dose Q, and both doses of B. Input \nvalues used in the model are based on immunogenicity data.\n•The effectiveness of the 3rd dose of MenACWY  (e.g., Q -P-P) is assumed to be the \nsame as the 2nd dose.\n•Incidence rate in the absence of vaccination is unknown, we used the most recent \npre-vaccine era data in our study.\n•The market price of GSK's pentavalent vaccine is not known with certainty; our \nmodel used the same market cost as the GSK model.Limitations\n41Q=Quadrivalent ( MenACWY ) vaccine; B= MenB  vaccine; P=Pentavalent ( MenABCWY ) vaccine.\n•Not accounting for additional benefits of potential protection against gonorrhea.\n-Possible benefits arise from changing from Q -Q to P -P , and from no vaccination vs. vaccination strategies. \n•Not including potential increases in vaccine uptake, and fewer adverse events due \nto fewer vaccine injections (i.e., P replacement of QB ).\n•Vaccine coverage inputs in this version of the model are consistent with current \nrecommendations, age -based use of Q vaccines and shared clinical decision -making \n(SCDM) use of B -component vaccines. Therefore, potential changes to the \nSCDM/routine status of B -component vaccines  were not incorporated into this \nversion of the model .Limitations\n42Q=Quadrivalent ( MenACWY ) vaccine; B= MenB  vaccine; P=Pentavalent ( MenABCWY ) vaccine.\n•PICO 1: \n-Q-P-B was found to be cost -saving relative to the current recommendation (vs. Q -QB-B).\n•PICO 2: \n-P-P could improve health outcomes, but costs $11.3 million per QALY saved (vs. Q -Q).\n•PICO 3: \n-Q-P-P could improve health outcomes, but estimated economic value varied depending on the \ncomparator:\n•Q-P-P is cost -saving compared to Q -QB-B.\n•Q-P-P costs $4.5 million per QALY gained more than Q -P-B.Summary\n43Q=Quadrivalent ( MenACWY ) vaccine; P=Pentavalent ( MenABCWY ) vaccine; IMD=Invasive meningococcal disease; QALY=Quality -adjusted life year.\nFor more information, contact CDC/ATSDR\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov           www.atsdr.cdc.gov \nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention and the Agency for Toxic Substances and Disease Registry.\nThank you!", "summary": "Economic Analyses of GSK MenABCWY  Vaccinations  among Adolescents in the United States Xiaoyu Donga, PhD, Andrew J Leidnera, PhD, Sarah F Schilliea, MD,  Lucy Alexandra McNamaraa, PhD a National Center for Immunization & Respiratory Diseases, CDC Disclaimers: The findings and conclusions in this report are those of the authors and do not necessarily represent the  views of the Centers for Disease Control and Prevention. National Center for Immunization & Respiratory Diseases ACIP Meeting…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-23-24-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/02-Mening-Dong-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 44}
{"title": "03 mening Schillie 508", "content": "GRADE/Evidence to Recommendations Framework (EtR) \nfor GSK Pentavalent (MenABCWY) Vaccine\nSarah F. Schillie, MD, MPH, MBA\nAdvisory Committee on Immunization Practices\nOctober 24, 2024National Center for Immunization & Respiratory Diseases\n1\nMeningococcal Vaccine Recommendations \nRoutine schedule \n–One MenACWY* dose at age 11 –12 years and a booster at age 16 years \n–Two MenB** doses at age 16 –23 years (shared clinical decision -making [SCDM])\n•Preferred age range: 16 –18 years \nIncreased risk, MenACWY* \n–Asplenia, complement deficiency, complement inhibitor use, and HIV infection\n–Some microbiologists\n–Exposure during an outbreak \n–Travel to hyperendemic areas \n–First -year college students (if not previously vaccinated at age ≥16 years)\nIncreased risk, MenB**\n–Asplenia, complement deficiency, and complement inhibitor use \n–Some microbiologists \n–Exposure during an outbreak\n*MenACWY vaccines are interchangeable; **MenB vaccines are not interchangeable2\nTwo new MenABCWY vaccines:\n–Pfizer (Penbraya, ACIP vote October 2023)\n–GSK (ACIP vote anticipated February 2025)\nEach vaccine is a combination of an existing:\n–MenACWY vaccine\n–MenB vaccine\nEach vaccine assessed separately by Work Group\n–Lack of data directly comparing Pfizer and GSK Pentavalent vaccinesPentavalent MenABCWY Vaccines\nand\n3\nPfizer and GSK MenABCWY Vaccines\nPfizer (Penbraya) GSK*\nACWY component Nimenrix (not licensed in U.S.) Menveo\nB component Trumenba Bexsero\nSchedule 2 doses, 6 months apart 2 doses, 6 months apart*\nAge 10–25 years 10–25 years*\n*Vaccine not yet licensed in U.S. and this slide represents anticipated schedule and age indications 4\nPolicy Questions\nPICO 1:\nShould the GSK pentavalent vaccine be included as an option for MenACWY/MenB \nvaccination in people currently recommended to receive both vaccines at the same visit?\n– For example, 16 year- olds*\nPICO 2:\nShould the GSK pentavalent vaccine be included as an option for people currently recommended to receive MenACWY only?\n–For example, 11 –12 year -olds\nPICO 3:\nShould the GSK pentavalent vaccine be included as an option for people currently recommended to receive MenB only?\n– For example, during a serogroup B outbreak\n*16 year -olds who decide to receive the MenB vaccine based on shared clinical decision -making5\nCombined Policy and PICO Questions\n6Policy QuestionShould the pentavalent vaccine be included as an option for people currently \nrecommended to receive MenACWY and MenB, MenACWY only, or MenB only ?\nPopulationAll individuals aged ≥10 years currently recommended to receive MenACWY+MenB, \nMenACWY , or MenB vaccine\nIntervention Vaccination with the pentavalent vaccine\nComparison Vaccination with currently licensed MenACWY+MenB, MenACWY , or MenB vaccine\nOutcomes•Meningococcal disease caused by serogroups A, B, C, W, and Y \n•Short- term immunity\n•Persistent immunity\n•Interference with other recommended vaccines administered concurrently\n•Serious adverse events\n•Non -serious adverse events\nOutcomes Table\nOutcome Importance* Included in \nEvidence Profile\nMeningococcal disease caused by serogroups \nA, B, C, W, and YCritical Yes\nPersistent immunity Important Yes\nShort -term immunity Critical Yes\nInterference with other recommended vaccines administered concurrentlyImportant Yes\nSerious adverse events Critical Yes\nNon -serious adverse events Important Yes\n*Three options:  critical, important but not critical, of limited importance for decision making\n7\nHow PICOs Translate into Schedule Options for \nHealthy Adolescents\n8OptionsDose at age \n11—12 yearsDose at age  \n16 yearsDose at age  \n16 years\nStandard of care (MenACWY only) Q Q -\nStandard of care (MenACWY + MenB) Q Q+B B\nPICO 1 (MenABCWY as option for MenACWY + MenB) Q P B\nPICO 2 (MenABCWY as option for MenACWY) P P B\nPICO 3 (MenABCWY as option for MenB) Q P P\nCombination of all 3 PICOs P P P\nLegend\nQ = MenACWY (quadrivalent)\nB = MenB\nP = MenABCWY (pentavalent)\nEtR Domain Question\nPublic health \nproblemIs invasive meningococcal disease a problem of public health \nimportance?\nBenefits and \nharmsHow substantial are the desirable anticipated effects?\nHow substantial are the undesirable  anticipated effects?\nDo the desirable anticipated effects outweigh the undesirable effects?\nWhat is the overall certainty of the evidence for the critical outcomes?\nValues Does the target population feel the desirable effects are large relative \nto the undesirable effects?\nIs there important variability in how patients value the outcome?\nAcceptability Is the intervention acceptable to key stakeholders?\nResource use Is the intervention a reasonable and efficient allocation of resources?\nEquity What would be the impact of the intervention on health equity?\nFeasibility Is the intervention feasible to implement?\n9\nPublic health problem\nIs invasive meningococcal disease a problem of public health importance?\nMeningococcal Disease\nMost often presents as meningitis or bacteremia\nProgresses rapidly\n10–15% of cases are fatal (even with appropriate antibiotic \ntherapy)\n~20% of survivors experience long -term sequelae\n–Cognitive deficits\n–Hearing loss\n–Limb amputations\n11\nPublic Health Problem\nIs invasive meningococcal disease a problem of public health importance?\nNo Probably \nnoProbably \nyesYes VariesDon’t \nknow\nPICO 1 (QPB vs. QQBB):\nMenABCWY vs. MenACWY + MenBX\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY vs. MenACWYX\nPICO 3 (QPP vs. QQBB):  \nMenABCWY vs. MenB  X\nPICO 1 (QPB vs. QQBB):\nMenABCWY vs. MenACWY + MenBX\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY vs. MenACWYX\nPICO 3 (QPP vs. QQBB):  \nMenABCWY vs. MenB  X\n12\nBenefits and harms\n- How substantial are the desirable anticipated effects?\n- How substantial are the undesirable anticipated effects?\n- Do the desirable effects outweigh the undesirable effects?\nStudies Included in Review of Evidence\n14Study ID(s) Location(s)Study \nDesignPhase Blinding PopulationAuthor, year or \nStudy IDPeriod\nNCT01210885\nNCT01367158 \nNCT02451514Chile, Colombia, \nPanamaRCT IIObserver -\nblindHealthy, immuno -naïve individuals aged \n11-18 yearsSaez -Llorens 2015a Dec 2010— Jul 2011\nSaez -Llorens 2015b Jul 2011— Jul 2012\nOpen- label*Prior participants + individuals w/o \nmeningococcal vaccine historySaez -Llorens 2018 Jun 2015— Dec 2015\nNCT01272180\nNCT01992536Poland, USA RCT IIObserver -\nblindHealthy, immuno -naïve individuals aged \n10-25 yearsBlock 2015 Aug 2011— Sep 2012\nSzenborn 2018 Dec 2013— Apr 2015\nNCT02140762 \nNCT02285777USA RCT IIbObserver -\nblindHealthy, immuno -naïve individuals aged \n10-18 yearsWelsch 2018 May 2014— Jun 2015\nNCT02212457\nNCT02946386Finland, Poland RCT IIbObserver -\nblindHealthy, immuno -naïve individuals aged \n10-18 yearsVesikari 2021Aug 2014— Mar 2016\nNov 2016— Feb 2018\nNCT03587207 Czechia RCT II Open- labelHealthy, immuno -naïve individuals aged \n10-25 yearsBeran 2021 Jul 2018— Dec 2018\nNCT04502693Australia, Canada, \nCzechia, Estonia, \nFinland, Turkey, USARCT IIIObserver -\nblindHealthy individuals aged 10 -25 years w/o \nhistory of meningococcal disease or \nvaccinationv72_72 Aug 2020— Sep 2022\nNCT04707391 Argentina, Australia, \nCanada, USARCT IIIObserver -\nblindHealthy individuals aged 15 -25 years \nvaccinated with MenACWY ≥4 years prior \nand w/o history of meningococcal diseaseMenABCWY_019 Jan 2021— Sep 2023\n*This extension study did not randomize participants. All prior participants were given a single dose of MenABCWY, while all new ly enrolled participants were given two doses of MenABCWY.\nShort- term immunity one month after one dose\nMenABCWY vs MenACWY\nShort -Term Immunity After One Dose for Healthy Persons\n1If >1 study included, effects and confidence intervals derived from a random -effects meta -analysis are presented; if one study i ncluded, traditional Wald confidence intervals are presented.\n2Includes potential conflicts of interest that are not factored into the grading of the certainty of evidence.\n3Includes one study with concomitant administration of MenB; meta -analysis suggested no statistically significant subgroup differ ences.\n4hSBA titers are the established correlate of protection for serogroup C meningococcal disease. This correlation is assumed to  extend to other serogroups, but direct evidence for these serogroups is limited. Goldschneider \net al. Human immunity to the meningococcus. I. The role of humoral antibodies. J Exp Med. 1969;129(6):1307 –26. 16Certainty assessment No. of patients Effect1\nCertainty Importance No. of \nstudiesStudy \ndesignRisk of \nbiasInconsistency Indirectness ImprecisionOther \nconsiderations2GSK \nMenABCWYComparatorRelative effect \nRR (95% CI)Absolute effect\nRD (95% CI) \nper 100,000\nShort -term immunity vs MenACWY (follow -up: 1 month) Serogroup  A\nModerate Critical\n43 Randomized \ntrialsNot \nseriousNot serious Serious4 Not serious GSK funded914 1,093 0.94 (0.86, 1.01)5,437 fewer (11,705 \nfewer to 832 more)\nSerogroup C\n926 1,105 1.03 (0.97, 1.10)2,726 more (2,545 \nfewer to 7,997 more)\nSerogroup W\n926 1,106 1.02 (1.00, 1.04)1,930 more (314 to \n3,546 more)\nSerogroup Y\n929 1,109 0.98 (0.93, 1.03)1,930 fewer (6,528 \nfewer to 2,668 more)\nShort -Term Immunity After One Dose for Persons at Increased Risk\n1If >1 study included, effects and confidence intervals derived from a random -effects meta -analysis are presented; if one study i ncluded, traditional Wald confidence intervals are presented.\n2Includes potential conflicts of interest that are not factored into the grading of the certainty of evidence.\n3Includes one study with concomitant administration of MenB; meta -analysis suggested no statistically significant subgroup differ ences.\n4hSBA titers are the established correlate of protection for serogroup C meningococcal disease. This correlation is assumed to  extend to other serogroups, but direct evidence for these serogroups is limited. Goldschneider \net al. Human immunity to the meningococcus. I. The role of humoral antibodies. J Exp Med. 1969;129(6):1307 –26. \n5Studies did not include persons at increased risk.17Certainty assessment No. of patients Effect1\nCertainty Importance No. of \nstudiesStudy \ndesignRisk of \nbiasInconsistency Indirectness ImprecisionOther \nconsiderations2GSK \nMenABCWYComparatorRelative effect \nRR (95% CI)Absolute effect\nRD (95% CI) \nper 100,000\nShort -term immunity vs MenACWY (follow -up: 1 month) Serogroup  A\nLow Critical\n43 Randomized \ntrialsNot \nseriousNot seriousVery \nserious4,5 Not serious GSK funded914 1,093 0.94 (0.86, 1.01)5,437 fewer (11,705 \nfewer to 832 more)\nSerogroup C\n926 1,105 1.03 (0.97, 1.10)2,726 more (2,545 \nfewer to 7,997 more)\nSerogroup W\n926 1,106 1.02 (1.00, 1.04)1,930 more (314 to \n3,546 more)\nSerogroup Y\n929 1,109 0.98 (0.93, 1.03)1,930 fewer (6,528 \nfewer to 2,668 more)\nShort- term immunity one month after \nseries completion\nTwo doses of MenABCWY vs two doses of MenB\nShort -Term Immunity After Series* Completion for Healthy Persons\n19*MenABCWY and MenB given on a 0,6 month schedule\n1If >1 study included, effects and confidence intervals derived from a random -effects meta -analysis are presented; if one study i ncluded, traditional Wald confidence intervals are presented.\n2Includes potential conflicts of interest that are not factored into the grading of the certainty of evidence.\n3Only one study included, therefore results are consistent by default.\n4hSBA titers are the established correlate of protection for serogroup C meningococcal disease. This correlation is assumed to  extend to other serogroups, but direct evidence for these serogroups is limited. Goldschneider \net al. Human immunity to the meningococcus. I. The role of humoral antibodies. J Exp Med. 1969;129(6):1307 –26. Certainty assessment No. of patients Effect1\nCertainty Importance No. of \nstudiesStudy \ndesignRisk of \nbiasInconsistency Indirectness ImprecisionOther \nconsiderations2GSK \nMenABCWYComparatorRelative effect \nRR (95% CI)Absolute effect\nRD (95% CI) \nper 100,000\nShort -term immunity after series completion vs MenB series (follow -up: 1 month) fHbp\nModerate Critical\n1Randomized \ntrialsNot \nseriousNone3 Serious4 Not serious GSK funded738 707 1.01 (0.99, 1.04)1,300 more (896 \nfewer to 3,496 more)\nNadA\n734 707 0.98 (0.96, 1.00)1,800 fewer (3,526 to \n74 fewer)\nNHBA\n738 711 0.98 (0.96,1.00)2,200 fewer (4,110 to \n290 fewer)\nPorA\n709 684 0.91 (0.86, 0.96)7,300 fewer (11,560 \nto 3,040 fewer)\nShort -Term Immunity After Series* Completion for Persons at Increased Risk\n20*MenABCWY and MenB given on a 0,6 month schedule\n1If >1 study included, effects and confidence intervals derived from a random -effects meta -analysis are presented; if one study i ncluded, traditional Wald confidence intervals are presented.\n2Includes potential conflicts of interest that are not factored into the grading of the certainty of evidence.\n3Only one study included, therefore results are consistent by default.\n4hSBA titers are the established correlate of protection for serogroup C meningococcal disease. This correlation is assumed to  extend to other serogroups, but direct evidence for these serogroups is limited. Goldschneider \net al. Human immunity to the meningococcus. I. The role of humoral antibodies. J Exp Med. 1969;129(6):1307 –26. \n5Studies did not include persons at increased risk.Certainty assessment No. of patients Effect1\nCertainty Importance No. of \nstudiesStudy \ndesignRisk of \nbiasInconsistency Indirectness ImprecisionOther \nconsiderations2GSK \nMenABCWYComparatorRelative effect \nRR (95% CI)Absolute effect\nRD (95% CI) \nper 100,000\nShort -term immunity after series completion vs MenB series (follow -up: 1 month) fHbp\nLow Critical\n1Randomized \ntrialsNot \nseriousNone3 Very \nserious4,5 Not serious GSK funded738 707 1.01 (0.99, 1.04)1,300 more (896 \nfewer to 3,496 more)\nNadA\n734 707 0.98 (0.96, 1.00)1,800 fewer (3,526 to \n74 fewer)\nNHBA\n738 711 0.98 (0.96,1.00)2,200 fewer (4,110 to \n290 fewer)\nPorA\n709 684 0.91 (0.86, 0.96)7,300 fewer (11,560 \nto 3,040 fewer)\nLong -term immunity two years after series \ncompletion\nTwo doses of MenABCWY vs two doses of MenB\nLong -Term Immunity After Series* Completion for Healthy Persons\n22Certainty assessment No. of patients Effect1\nCertainty Importance No. of \nstudiesStudy \ndesignRisk of \nbiasInconsistency Indirectness ImprecisionOther \nconsiderations2GSK \nMenABCWYComparatorRelative effect \nRR (95% CI)Absolute effect\nRD (95% CI) \nper 100,000\nLong -term immunity after series completion vs MenACWY (follow -up: 2 years)\n0\nLong -term immunity after series completion vs MenB (follow -up: 2 years fHbp\nLow Important\n1Randomized \ntrialsNot \nseriousNone3 Serious4 Serious5 GSK funded70 119 1.46 (0.84, 2.54)8,000 more (4,379 \nfewer to 20,379 more)\nNadA\n72 121 0.90 (0.77, 1.06)8,000 fewer (20,228 \nfewer to 4,228 more)\nNHBA\n71 122 1.31 (0.86, 2.00)9,000 more (4,770 \nfewer to 22,770 more)\nPorA\n71 121 1.17 (0.61, 2.22)2,000 more (9,069 \nfewer to 13,069 more)\n*MenABCWY and MenB given on a 0,6 month schedule\n1If >1 study included, effects and confidence intervals derived from a random -effects meta -analysis are presented; if one study i ncluded, traditional Wald confidence intervals are presented.\n2Includes potential conflicts of interest that are not factored into the grading of the certainty of evidence.\n3Only one study included, therefore results are consistent by default.\n4hSBA titers are the established correlate of protection for serogroup C meningococcal disease. This correlation is assumed to  extend to other serogroups, but direct evidence for these serogroups is limited. Goldschneider \net al. Human immunity to the meningococcus. I. The role of humoral antibodies. J Exp Med. 1969;129(6):1307 –26. \n5Based on both the precision of the relative and absolute effects and the relatively small sample size\nLong -Term Immunity After Series* Completion for Persons at Increased Risk\n23Certainty assessment No. of patients Effect1\nCertainty Importance No. of \nstudiesStudy \ndesignRisk of \nbiasInconsistency Indirectness ImprecisionOther \nconsiderations2GSK \nMenABCWYComparatorRelative effect \nRR (95% CI)Absolute effect\nRD (95% CI) \nper 100,000\nLong -term immunity after series completion vs MenACWY (follow -up: 2 years)\n0\nLong -term immunity after series completion vs MenB (follow -up: 2 years fHbp\nVery low Important\n1Randomized \ntrialsNot \nseriousNone3 Very \nserious4,5 Serious6 GSK funded70 119 1.46 (0.84, 2.54)8,000 more (4,379 \nfewer to 20,379 more)\nNadA\n72 121 0.90 (0.77, 1.06)8,000 fewer (20,228 \nfewer to 4,228 more)\nNHBA\n71 122 1.31 (0.86, 2.00)9,000 more (4,770 \nfewer to 22,770 more)\nPorA\n71 121 1.17 (0.61, 2.22)2,000 more (9,069 \nfewer to 13,069 more)\n*MenABCWY and MenB given on a 0,6 month schedule\n1If >1 study included, effects and confidence intervals derived from a random -effects meta -analysis are presented; if one study i ncluded, traditional Wald confidence intervals are presented.\n2Includes potential conflicts of interest that are not factored into the grading of the certainty of evidence.\n3Only one study included, therefore results are consistent by default.\n4hSBA titers are the established correlate of protection for serogroup C meningococcal disease. This correlation is assumed to  extend to other serogroups, but direct evidence for these serogroups is limited. Goldschneider \net al. Human immunity to the meningococcus. I. The role of humoral antibodies. J Exp Med. 1969;129(6):1307 –26. \n5Studies did not include persons at increased risk\n6Based on both the precision of the relative and absolute effects and the relatively small sample size\nAdverse events\nSerious\nNon -serious after one dose\nNon -serious after ≥2 doses\nSerious Adverse Events Assessed as Possibly Related to Vaccination, \nRegardless of Dosing Schedule\n25StudyNumber\nPentavalent MenACWY MenB MenACWY/MenB\nSaez -Llorens 201510 0 -- --\nBlock 2015 0 0 0 --\nWelsch 2018 0 0 -- --\nVesikari 20212 \n(seizure, connective \ntissue disorder)-- 0 --\nBeran 2021 0 01 \n(syncope)0\nv72_722 1 \n(neuromyelitis optica)1\n(pyrexia)1\n(ulcerative colitis)--\nMenABCWY_019 0 0 -- --\n1One related event during extension study in a recipient of a MenABCWY that contained ¼ of the usual OMV component\n2These were reported as related to vaccination by investigators; however, they were not considered adverse drug reactions rela ted to vaccination after GSK and independent evaluation\nSerious Adverse Events Assessed as Related to Vaccination for Healthy Persons and Those at Increased \nRisk\n26Certainty assessment No. of patients Effect1\nCertainty Importance No. of \nstudiesStudy \ndesignRisk of \nbiasInconsistency Indirectness ImprecisionOther \nconsiderations2GSK \nMenABCWYComparatorRelative effect \nRR (95% CI)Absolute effect\nRD (95% CI)\nper 100,000\n7Randomized \ntrialsNot \nseriousNot serious Not serious Serious3GSK funded4,016 \n(0-2 events \nper study)3,921 \n(0-2 events \nper study)1.03 (0.30, 3.60)6 fewer (150 fewer \nto 138 more)Moderate Critical\n1If >1 study included, effects and confidence intervals derived from a random -effects meta -analysis are presented; if one study i ncluded, traditional Wald confidence intervals are presented\n2Includes potential conflicts of interest that are not factored into the grading of the certainty of evidence.\n3Based on the precision of the relative effect\n4Studies did not include persons at increased risk.Certainty assessment No. of patients Effect1\nCertainty Importance No. of \nstudiesStudy \ndesignRisk of \nbiasInconsistency Indirectness ImprecisionOther \nconsiderations2GSK \nMenABCWYComparatorRelative effect \n(95% CI)Absolute effect\nRD (95% CI)\nper 100,000\n7Randomized \ntrialsNot \nseriousNot serious Serious4Serious3GSK funded4,016 \n(0-2 events \nper study)3,921 \n(0-2 events \nper study)1.03 (0.30, 3.60)6 fewer (150 fewer \nto 138 more)Low CriticalHealthy Persons\nPersons at Increased Risk\nThe a pparent directional discrepancy between RR and RD is due to a continuity correction for the RR to adjust zeros \nNon -Serious Adverse Events for Healthy Persons\n27Certainty assessment No. of patients Effect1\nCertainty Importance No. of \nstudiesStudy \ndesignRisk of \nbiasInconsistency Indirectness ImprecisionOther \nconsiderations2GSK \nMenABCWYComparatorRelative effect \nRR (95% CI)Absolute effect\nRD (95% CI)\nper 100,000\nAfter one dose\n4\nRandomized \ntrialsNot \nseriousvs MenB\nNot serious Not serious Not serious GSK funded 2,766 2,315 1.00 (0.98, 1.02)106 more (1,434 \nfewer to 1,647 more)High Important\n1vs MenB/MenACWY\nNone3 Not serious Serious4 GSK funded 100 204 0.93 (0.86, 1.00)6,588 fewer (13,337 \nfewer to 161 more)Moderate Important\n6vs MenACWY\nNot serious Not serious Serious5 GSK funded 2,683 1,190 1.97 (1.65, 2.36)42,626 more (36,291 \nto 48,962 more)Moderate Important\nAfter two or more doses\n2\nRandomized \ntrialsNot \nseriousvs MenB\nNot serious Not serious Not serious GSK funded 1,680 2,660 1.00 (0.98, 1.02)135 more (1,837 \nfewer to 2,107 more)High Important\n2vs MenACWY\nNot serious Not serious Serious5 GSK funded 1,935 779 2.19 (1.89, 2.54)43,148 more (38,813 \nto 47,484 more)Moderate Important\n1f >1 study included, effects and confidence intervals were derived from a random -effects meta -analysis; if  one study included, effect and confidence intervals were derived using the Wald method\n2Includes potential conflicts of interest that are not factored into the grading of the certainty of evidence.\n3Only one study included, therefore results are consistent by default.\n4Based on the imprecision of the absolute effect and the relatively small sample size\n5Based on the imprecision of the relative and absolute effects, despite the relatively large sample size.\nNon -Serious Adverse Events for Persons at Increased Risk\n28Certainty assessment No. of patients Effect1\nCertainty Importance No. of \nstudiesStudy \ndesignRisk of \nbiasInconsistency Indirectness ImprecisionOther \nconsiderations2GSK \nMenABCWYComparatorRelative effect \nRR (95% CI)Absolute effect\nRD (95% CI)\nper 100,000\nAfter one dose\n4\nRandomized \ntrialsNot \nseriousvs MenB\nNot serious Serious3Not serious GSK funded 2,766 2,315 1.00 (0.98, 1.02)106 more (1,434 \nfewer to 1,647 more)Moderate Important\n1vs MenB/MenACWY\nNone4 Serious3 Serious5 GSK funded 100 204 0.93 (0.86, 1.00)6,588 fewer (13,337 \nfewer to 161 more)Low Important\n6vs MenACWY\nNot serious Serious3 Serious6 GSK funded 2,683 1,190 1.97 (1.65, 2.36)42,626 more (36,291 \nto 48,962 more)Low Important\nAfter two or more doses\n2\nRandomized \ntrialsNot \nseriousvs MenB\nNot serious Serious3Not serious GSK funded 1,680 2,660 1.00 (0.98, 1.02)135 more (1,837 \nfewer to 2,107 more)Moderate Important\n2vs MenACWY\nNot serious Serious3 Serious6 GSK funded 1,935 779 2.19 (1.89, 2.54)43,148 more (38,813 \nto 47,484 more)Low Important\n1f >1 study included, effects and confidence intervals were derived from a random -effects meta -analysis; if  one study included, effect and confidence intervals were derived using the Wald method\n2Includes potential conflicts of interest that are not factored into the grading of the certainty of evidence.\n3Studies did not include persons at increased risk.\n4Only one study included, therefore results are consistent by default.\n5Based on the imprecision of the absolute effect and the relatively small sample size\n6Based on the imprecision of the relative and absolute effects, despite the relatively large sample size.\nSummary of Evidence\nPICO 1:  Certainty PICO 2:  Certainty PICO 3:  Certainty\nOutcome Healthy Increased Risk Healthy Increased Risk Healthy Increased Risk\nCritical outcomes\nMeningococcal disease \ncaused by serogroups A, B, \nC, W, and Y-- -- -- -- -- --\nShort -term immunity Moderate Low Moderate Low Moderate Low\nSerious adverse events Moderate Low Moderate Low Moderate Low\nImportant outcomes\nInterference with other \nrecommended vaccines \nadministered concurrently-- -- -- -- -- --\nNon -serious adverse \neventsModerate Low Moderate Low Moderate Low\nPersistent immunity Low** Very low** -- -- Low Very low\n*Three options:  critical, important but not critical, of limited importance for decision making; **MenB only 29\nHow substantial are the desirable  anticipated effects?Benefits and Harms\nMinimal Small Moderate Large VariesDon’t \nknow\nPICO 1 (QPB vs. QQBB):\nMenABCWY vs. MenACWY + MenBX\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY vs. MenACWYX X X\nPICO 3 (QPP vs. QQBB):  \nMenABCWY vs. MenB  X\nPICO 1 (QPB vs. QQBB):\nMenABCWY vs. MenACWY + MenBX\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY vs. MenACWYX\nPICO 3 (QPP vs. QQBB):  \nMenABCWY vs. MenB  X\n30\nHow substantial are the undesirable  anticipated effects?Benefits and Harms\nMinimal Small Moderate Large VariesDon’t \nknow\nPICO 1 (QPB vs. QQBB):\nMenABCWY vs. MenACWY + MenBX\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY vs. MenACWYX X\nPICO 3 (QPP vs. QQBB):  \nMenABCWY vs. MenB  X X\nPICO 1 (QPB vs. QQBB):\nMenABCWY vs. MenACWY + MenBX\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY vs. MenACWYX\nPICO 3 (QPP vs. QQBB):  \nMenABCWY vs. MenB  X\n31\nDo the desirable effects outweigh the undesirable effects?Benefits and Harms\nFavors \ninterventionFavors \ncomparisonFavors \nbothFavors \nneitherVariesDon’t \nknow\nPICO 1 (QPB vs. QQBB):\nMenABCWY vs. MenACWY + MenBX\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY vs. MenACWYX X X\nPICO 3 (QPP vs. QQBB):  \nMenABCWY vs. MenB  X X\nPICO 1 (QPB vs. QQBB):\nMenABCWY vs. MenACWY + MenBX\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY vs. MenACWYX X X\nPICO 3 (QPP vs. QQBB):  \nMenABCWY vs. MenB  X X X\n32\nWhat is the overall certainty of this evidence for the critical outcomes?Benefits and Harms:  Short -term Immunity\nNo studies \nfoundVery low Low Moderate High\nPICO 1 (QPB vs. QQBB):\nMenABCWY vs. MenACWY + MenBX X\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY vs. MenACWYX X\nPICO 3 (QPP vs. QQBB):  \nMenABCWY vs. MenB  X X\nPICO 1 (QPB vs. QQBB):\nMenABCWY vs. MenACWY + MenBX X\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY vs. MenACWYX X\nPICO 3 (QPP vs. QQBB):  \nMenABCWY vs. MenB  X X\n33\nWhat is the overall certainty of this evidence for the critical outcomes?Benefits and Harms:  Serious Adverse Events\nNo studies \nfoundVery low Low Moderate High\nPICO 1 (QPB vs. QQBB):\nMenABCWY vs. MenACWY + MenBX X\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY vs. MenACWYX X\nPICO 3 (QPP vs. QQBB):  \nMenABCWY vs. MenB  X X\nPICO 1 (QPB vs. QQBB):\nMenABCWY vs. MenACWY + MenBX X\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY vs. MenACWYX X\nPICO 3 (QPP vs. QQBB):  \nMenABCWY vs. MenB  X X\n34\nValues\n- Does the target population feel that the desirable effects are large relative to \nthe undesirable effects?\n- Is there important uncertainty about or variability in how much people value \nthe main outcome?\nMenACWY Coverage among Adolescents (2023)\n≥ 1 dose \namong 13 yr olds85.1%\n≥ 2 doses \namong 17 yr olds59.7%\nPingali  C et al. MMWR Morb Mortal Wkly Rep 2024.36\nMenB Coverage among Adolescents (2023)\n≥ 1 dose \namong 17 yr olds32.4%\n≥ 2 doses \namong 17 yr olds12.8%\nPingali  C et al. MMWR Morb Mortal Wkly Rep 2024.37\nValues\nMost adolescents and parents prefer a simplified \nmeningococcal vaccine schedule (with fewer injections and fewer visits):\n–89.6% of 16–23 year- olds\n–69.1% of parents  \nBegum S et al. Infect Dis Ther 2024 (note GSK affiliation) 38\nValues\nDoes the target population feel that the desirable effects are large relative to the \nundesirable effects? \nNo Probably \nnoProbably \nyesYes VariesDon’t \nknow\nPICO 1 (QPB vs. QQBB):\nMenABCWY vs. MenACWY + MenBX\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY vs. MenACWYX\nPICO 3 (QPP vs. QQBB):  \nMenABCWY vs. MenB  X X\nPICO 1 (QPB vs. QQBB):\nMenABCWY vs. MenACWY + MenBX\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY vs. MenACWYX\nPICO 3 (QPP vs. QQBB):  \nMenABCWY vs. MenB  X X X\n39\nValues\nIs there important uncertainty about or variability in how much people value the \nmain outcome? \nImportant \nuncertainty \nor \nvariability Probably \nimportant \nuncertainty \nor variabilityProbably \nnot \nimportant \nuncertainty \nor variabilityNo \nimportant \nuncertainty \nor variabilityNo known \nundesirable \noutcomes\nPICO 1 (QPB vs. QQBB):\nMenABCWY vs. MenACWY + MenBX\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY vs. MenACWYX\nPICO 3 (QPP vs. QQBB):  \nMenABCWY vs. MenB  X\nPICO 1 (QPB vs. QQBB):\nMenABCWY vs. MenACWY + MenBX X\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY vs. MenACWYX X\nPICO 3 (QPP vs. QQBB):  \nMenABCWY vs. MenB  X X\nAcceptability\n- Is the intervention acceptable to key stakeholders?\nCombination Vaccines \nCDC’s General Best Practice Guidance for Immunization and American Academy \nof Pediatrics Red Book  both state a general preference for combination vaccines \nover separate injections of equivalent component vaccines1,2\n1General Best Practice Guidelines for Immunization. Best Practice Guidance of the ACIP . https://www.cdc.gov/vaccines/hcp/acip- recs/general -recs/index.html   \n2American Academy of Pediatrics. Red Book 2024 -27 Report of the Committee on Infectious Diseases. 33rd Edition.Potential advantages Potential disadvantages\n•Improved vaccine coverage rates\n•Timely catch -up immunizations\n•Reduced shipping and stocking costs\n•Reduced costs for extra health care visits necessitated by \ndeferral of vaccination\n•Facilitation of additional new vaccines into vaccination programs•Adverse events that might occur more frequently with \ncombination vaccines than with individual components\n•Confusion and uncertainty about selection of vaccine \ncombinations and schedules for subsequent doses \n•Extra doses of certain antigens in the combination product \n(MenB vaccine is more reactogenic than MenACWY vaccine)\n42\nPreference for Fewer Injections\nAdolescents prefer fewer injections due to injection site \ndiscomfort\nParents/caregivers prefer fewer injections to reduce number of physician visits\n–Parental work loss\nBegum S., et al. OFID ppS515- 6. IDWeek2023 (GSK affiliation). 43\nAcceptability\nIs the intervention acceptable to key stakeholders?\nNo Probably \nnoProbably \nyesYes VariesDon’t \nknow\nPICO 1 (QPB vs. QQBB):\nMenABCWY vs. MenACWY + MenBX X\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY vs. MenACWYX X\nPICO 3 (QPP vs. QQBB):  \nMenABCWY vs. MenB  X\nPICO 1 (QPB vs. QQBB):\nMenABCWY vs. MenACWY + MenBX\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY vs. MenACWYX\nPICO 3 (QPP vs. QQBB):  \nMenABCWY vs. MenB  X X\n44\nResource use\n- Is the intervention a reasonable and efficient allocation of resources?\nEconomic Analysis\n•PICO 1: Q-P-B was found to be cost -saving relative to the current \nrecommendation (vs. Q -Q-B-B).\n•PICO 2: P-P-N could improve health outcomes, but costs $11.3 \nmillion per QALY saved (vs. Q -Q-N).\n•PICO 3: Q-P-P is cost -saving compared to Q -Q-B-B.\nQ-P-P is $4.5 million per QALY saved more than Q -P-B.\n46\nResource Use\nIs the intervention a reasonable and efficient allocation of resources?\nNo Probably \nnoProbably \nyesYes VariesDon’t \nknow\nPICO 1 (QPB vs. QQBB):\nMenABCWY vs. MenACWY + MenBX X\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY vs. MenACWYX X\nPICO 3 (QPP vs. QQBB):  \nMenABCWY vs. MenB  X X\nPICO 1 (QPB vs. QQBB):\nMenABCWY vs. MenACWY + MenBX\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY vs. MenACWYX X\nPICO 3 (QPP vs. QQBB):  \nMenABCWY vs. MenB  X*\n*WG sentiment varied from no to yes 47\nEquity\n- What would be the impact on health equity?\nMeningococcal Disease Incidence by Race―United \nStates, 2015–2023*\nSource: NNDSS data with additional serogroup data from ABCs and state health departments. *2023 NNDSS data are preliminary.\nRace is unknown for 5-12% of cases per year00.050.10.150.20.250.30.35\n2015 2016 2017 2018 2019 2020 2021 2022 2023Incidence per 100,000\nYear\nWhite Black or African American American Indian or Alaska Native Asian or Pacific Islander\n49\nAverage Annual Meningococcal Disease Incidence by Race \namong 11 –20 year olds―United States, 2015–2023*\nSource: NNDSS data with additional serogroup data from ABCs and state health departments. *2023 NNDSS data are preliminary.\nRace is unknown for 6-15% of cases per year00.010.020.030.040.050.060.070.080.090.1\nWhite Black or African\nAmericanAmerican Indian or\nAlaska NativeAsian or Pacific\nIslanderIncidence per 100,000\n50\nMeningococcal Disease Incidence by Ethnicity ― \nUnited States, 2015 –2023*\nSource: NNDSS data with additional serogroup data from ABCs and state health departments. *2023 NNDSS data are preliminary.\nEthnicity is unknown for 2 -16% of cases per year00.020.040.060.080.10.120.140.16\n2015 2016 2017 2018 2019 2020 2021 2022 2023Incidence per 100,000\nYear\nHispanic or Latino Not Hispanic or Latino\n51\nAverage Annual Meningococcal Disease Incidence by Ethnicity \namong 11– 20 year olds―United States, 2015– 2023*\nSource: NNDSS data with additional serogroup data from ABCs and state health departments. *2023 NNDSS data are preliminary.\nEthnicity is unknown for 3 -27% of cases per year00.010.020.030.040.050.060.070.080.09\nHispanic or Latino Not Hispanic or LatinoIncidence per 100,000\n52\nMenB Vaccine Availability\nCounties with lower socioeconomic status (SES) had \nfewer MenB doses stocked\n–20 doses/100 adolescents for low SES counties\n                   vs.\n–28 doses/100 adolescents for high SES counties\nSchley et al.  BMC Publ Hlth 2024 (note:  Pfizer affiliation)53\nEquity and Shared Clinical Decision-Making\nProvider or patient awareness of a SCDM recommendation is a pre-\nrequisite for discussions with patients and could lead to health \ninequities\n–Only 51% of pediatricians and 31% of family physicians reported always or \noften discussing MenB vaccination\nPentavalent vaccine could potentially reduce disparities among those \nwho might be interested in MenB vaccination but who might not \nreceive clinical care that includes discussion of MenB vaccine\nGidengil et al. Vaccine 2023; Kempe et al. Pediatrics 2018.  54\nLack of MenB Vaccine Interchangeability\nLack of MenB vaccine interchangeability currently restricts \nexisting MenABCWY vaccine use to patients of providers stocking Pfizer MenB vaccine products\n55\nEquity\nWhat would be the impact on health equity\nReducedProbably \nreducedProbably \nno impactProbably \nincreasedIncreased VariesDon’t \nknow\nPICO 1 (QPB vs. QQBB):\nMenABCWY vs. MenACWY + MenBX X\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY vs. MenACWYX X X\nPICO 3 (QPP vs. QQBB):  \nMenABCWY vs. MenB  X\nPICO 1 (QPB vs. QQBB):\nMenABCWY vs. MenACWY + MenBX\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY vs. MenACWYX X\nPICO 3 (QPP vs. QQBB):  \nMenABCWY vs. MenB  X\n56\nFeasibility\n- Is the intervention feasible to implement?\nFeasibility\nChallenges with insurance or financial burdens related \nto pentavalent vaccine not expected\nGSK pentavalent vaccine would provide additional option and may reduce number of doses for some people\nLack of MenB vaccine interchangeability complicates stocking considerations\n58\nFeasibility\nIs the intervention feasible to implement?  \nNo Probably \nnoProbably \nyesYes VariesDon’t \nknow\nPICO 1 (QPB vs. QQBB):\nMenABCWY vs. MenACWY + MenBX X\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY vs. MenACWYX X\nPICO 3 (QPP vs. QQBB):  \nMenABCWY vs. MenB  X X\nPICO 1 (QPB vs. QQBB):\nMenABCWY vs. MenACWY + MenBX\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY vs. MenACWYX X\nPICO 3 (QPP vs. QQBB):  \nMenABCWY vs. MenB  X\n59\nEtR Domain QuestionWork Group \nDetermination – \nPICO 1Work Group \nDetermination – \nPICO 2Work Group \nDetermination – \nPICO 3\nPublic health \nproblemIs invasive meningococcal disease a problem of public health importance?Yes Yes Yes\nBenefits and harmsHow substantial are the desirable anticipated effects? Small Small Small\nHow substantial are the undesirable anticipated effects? Minimal Small Minimal\nDo the desirable anticipated effects outweigh the undesirable effects?Favors \ninterventionFavors intervention/ \ncomparison/bothFavors \nintervention/ \ncomparison/both\nWhat is the overall certainty of evidence? Low Low Low\nValues Does the target population feel the desirable effects are large relative to the undesirable effects?Yes Probably yes Probably yes/yes/\ndon’t know\nIs there important variability in how patients value the \noutcome?Probably not/no Probably/probably \nnotProbably/probably \nnot\nAcceptability Is the intervention acceptable to key stakeholders? Yes Probably yes Probably yes/yes\nResource use Is the intervention a reasonable and efficient allocation of \nresources?Yes Probably no/varies Varies\nEquity What would be the impact of the intervention on health equity?Probably \nincreasedProbably \nincreased/increasedProbably increased\nFeasibility Is the intervention feasible to implement? Yes Probably yes/yes Yes\n60\nBalance of Consequences\nUndesirable \nconsequences \nclearly outweigh \ndesirable \nconsequences in \nmost settingsUndesirable \nconsequences \nprobably \noutweigh \ndesirable \nconsequences in \nmost settingsThe balance \nbetween \ndesirable and \nundesirable \nconsequences is \nclosely balanced \nor uncertainDesirable \nconsequences \nprobably \noutweigh \nundesirable \nconsequences \nin most settingsDesirable \nconsequences \nclearly \noutweigh \nundesirable \nconsequences \nin most \nsettingsThere is \ninsufficient \nevidence to \ndetermine the \nbalance of \nconsequences\nPICO 1 (QPB vs. QQBB):\nMenABCWY vs. MenACWY + MenBX\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY vs. MenACWYX X\nPICO 3 (QPP vs. QQBB):  \nMenABCWY vs. MenB  X X X\nPICO 1 (QPB vs. QQBB):\nMenABCWY vs. MenACWY + MenBX\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY vs. MenACWYX X X\nPICO 3 (QPP vs. QQBB):  \nMenABCWY vs. MenB  X X X X\nWork Group Interpretation\nIs there sufficient information to move forward with a recommendation?  \nYes No\nPICO 1 (QPB vs. QQBB):\nMenABCWY vs. MenACWY + \nMenBX\nPICO 2 (PPB vs. QQBB or PP \nvs. QQ):\nMenABCWY vs. MenACWYX\nPICO 3 (QPP vs. QQBB):  \nMenABCWY vs. MenB  X\n62\nWork Group Interpretation\nWe do not \nrecommend the \ninterventionWe do \nrecommend the \nintervention\nPICO 1 (QPB vs. QQBB):\nMenABCWY vs. MenACWY + MenBX\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY vs. MenACWYX\nPICO 3 (QPP vs. QQBB):  \nMenABCWY vs. MenB  X X\n63\n64Comment Regarding Work Group Interpretation\nSeveral Work Group members noted that it would be important to \nharmonize recommendations between the GSK and Pfizer pentavalent \nvaccines\n–Unless there is a vaccine -specific reason to have a different \nrecommendation\n65Next Steps\nAn interim recommendation for the GSK vaccine could mirror the \nrecommendation made for the Pfizer vaccine last year\n–Accept PICO 1, reject PICOs 2 and 3\nRecommendations for use of both pentavalent vaccines could then be \nrevisited as part of future adolescent schedule deliberations if desired\n66Acknowledgements\nAvnika Amin\nLucy McNamara\nXiaoyu Dong\nRebecca Morgan\nDoug Campos -Outcalt\nNoele Nelson\nSusan Hariri\nLeAnne Fox\nJennifer Collins\nAmy Rubis\nThank you!\n67For more information, contact CDC\n1-800- CDC- INFO (232- 4636)\nTTY:  1 -888- 232- 6348    cdc.gov\nFollow us on X (Twitter) @CDCgov & @CDCEnvironment\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position o f \nthe U. S. Centers for Disease Control and Prevention.", "summary": "GRADE/Evidence to Recommendations Framework (EtR)  for GSK Pentavalent (MenABCWY) Vaccine Sarah F. Schillie, MD, MPH, MBA Advisory Committee on Immunization Practices October 24, 2024National Center for Immunization & Respiratory Diseases 1 Meningococcal Vaccine Recommendations  Routine schedule  –One MenACWY* dose at age 11 –12 years and a booster at age 16 years  –Two MenB** doses at age 16 –23 years (shared clinical decision -making [SCDM]) •Preferred age range: 16 –18 years  Increased…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-23-24-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/03-mening-Schillie-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 67}
{"title": "04 mening Schillie 508", "content": "Introduction to MenB -4C (Bexsero) Interval and Dosing \nLabel Change\nSarah F. Schillie, MD, MPH, MBA\nAdvisory Committee on Immunization Practices\nOctober 24, 2024National Center for Immunization & Respiratory Diseases\n1\n2MenB -4C (Bexsero) Interval Changes\nInitially licensed by FDA under an accelerated approval \nprocess\nNew immunogenicity data support changes to dosing schedule \n–No safety concerns\nFull FDA approval:  August 19, 2024\nNew dosing schedule aligned with MenB- FHbp  \n(Trumenba) \nhttps://www.fda.gov/media/90996/download?attachment  \nhttps://wayback.archive -it.org/7993/20190423064853/https://www.fda.gov/downloads/BiologicsBloodVaccines/Vaccines/ApprovedProduct s/UCM431447.pdf\n3Previous Recommendations (Consistent with Label)\nMenB -4C (Bexsero):  Previous MenB -FHbp  (Trumenba ):  Existing\nAdolescents:  \n2-dose series (0, ≥1 month)Adolescents:  2-dose series (0, 6 month)\nIf dose 2 is administered earlier than 6 months, \nadminister 3\nrd dose at least 4 months after dose 2\nPersistent complement component deficiencies, \nthose with complement inhibitor use, functional or \nanatomic asplenia, microbiologists routinely \nexposed to Neisseria meningitidis , or persons \naffected by an outbreak of serogroup B meningococcal disease: \n2-dose series (0, ≥1 month)Persistent complement component deficiencies, \nthose with complement inhibitor use, functional or \nanatomic asplenia, microbiologists routinely \nexposed to Neisseria meningitidis , or persons \naffected by an outbreak of serogroup B meningococcal disease:\n3-dose series (0, 1 –2, 6 months)\n3\n4New MenB- 4C (Bexsero) Label\nTwo-dose schedule: Administer a dose (0.5 mL) at 0 and 6 months. If the \nsecond dose is administered earlier than 6 months after the first dose, a \nthird dose should be administered at least 4 months after the second dose. \nThree -dose schedule: Administer a dose (0.5 mL) at 0, 1 –2, and 6 \nmonths. \nThe choice of dosing schedule may depend on the risk of exposure and \nthe individual’s susceptibility to meningococcal serogroup B disease.\n5Proposed ACIP Recommendations\nGiven the recent MenB- 4C (Bexsero) label change, ACIP will \nvote for updated recommendations\nProposed recommendations will achieve alignment between \nACIP recommendations for MenB- 4C (Bexsero) and:\n–FDA label\n–ACIP MenB -FHbp  (Trumenba ) recommendations\nEvidence to Recommendations \nFramework (Abridged) for \nMenB -4C (Bexsero) Interval and \nDosing Change\nPICO Questions\nPICO 1:\nAmong persons aged 16 –23 years recommended for MenB  vaccination based on \nshared clinical decision -making, should MenB -4C be administered on a 0, 6 month \ndosing interval, vs. a 0, ≥1 month dosing interval, for the prevention of invasive \nmeningococcal disease?\nPICO 2:\nAmong persons with persistent complement component deficiencies, those with \ncomplement inhibitor use, functional or anatomic asplenia, microbiologists routinely exposed to Neisseria meningitidis, or persons affected by an outbreak of serogroup B meningococcal disease , should MenB -4C be administered on a 0, 1 –2, 6 month \nschedule, vs. a 0, ≥1 month schedule, for the prevention of invasive meningococcal disease? \n7\nPICO Questions\nPICO 1:\nAmong persons aged 16 –23 years recommended for MenB  vaccination based on \nshared clinical decision -making, should MenB -4C be administered on a 0, 6 month \ndosing interval, vs. a 0, ≥1 month dosing interval, for the prevention of invasive \nmeningococcal disease?  ‘Yes‘ aligns with existing MenB -FHbp (Trumenba ) \nrecommendation\nPICO 2:\nAmong persons with persistent complement component deficiencies, those with \ncomplement inhibitor use, functional or anatomic asplenia, microbiologists routinely exposed to Neisseria meningitidis, or persons affected by an outbreak of serogroup B meningococcal disease , should MenB -4C be administered on a 0, 1 –2, 6 month \nschedule, vs. a 0, ≥1 month schedule, for the prevention of invasive meningococcal disease? ‘Yes‘ aligns with existing MenB -FHbp (Trumenba ) recommendation\n8\nPublic health problem\nIs invasive meningococcal disease a problem of public health importance?\n10Meningococcal Disease\nMost often presents as meningitis or bacteremia\nProgresses rapidly\n10–15% of cases are fatal (even with appropriate antibiotic \ntherapy)\n~20% of survivors experience long -term sequelae\n–Cognitive deficits\n–Hearing loss\n–Limb amputations\n00.020.040.060.080.10.12\n2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023Incidence per 100,000\nYearB C Y W Other\nSource: NNDSS data with additional serogroup data from Active Bacterial Core surveillance (ABCs) and state health departments  \n*2023 data are preliminaryTrends in Meningococcal Disease Incidence by \nSerogroup – United States, 2006 –2023*\n11\n12Persons at Increased Risk for Serogroup B Meningococcal Disease\nEstimated increased \nriskEstimated \npopulation size\nPersistent complement component deficiency Up to 10,000 -fold 86,0001\nComplement inhibitor use 2,000- fold 3,0002\nAnatomic or functional aspleniaCase fatality -rate up \nto 40 -70%>80,0003\nMicrobiologists routinely exposed to N. meningitidis 120- fold 100,0004\nPersons exposed during an outbreak Up to 1,400- fold Up to ~33,000\nMeningococcal Vaccination: Recommendations of the Advisory Committee on Immunization Practices, United States, 2020 | MMWR (c dc.gov)  \n1Estimated prevalence in all ages of 0.03% (Densen R. Clin Exp Immunol. 1991) though many may be undiagnosed.\n2Preliminary estimate projected from 2017 claims data ( Marketscan and Medicaid)\n3Based on estimated 100,000 persons with sickle cell disease (CDC data), minus the ~20,000 children aged <10 years with diseas e (estimated 1,800 -2,000 children identified with sickle cell disease annually\nthrough newborn screening, with 95% survival to age 18 years). \n4Bureau of Labor Statistics, 2016. Adjusted to estimate personnel with occupational exposure to N. meningitidis. https://www.b ls.gov/ooh/life -physical- and-social- science/microbiologists.htm#tab -1,\nhttps://www.bls.gov/ooh/healthcare/medical- and-clinical- laboratory -technologists- and-technicians.htm\nMeningococcal Disease Outbreaks 2022 -Present\nOutbreak Outbreak Period Serogroup Cases (deaths)\nFlorida MSM December 2021 – February 2023 C 46 (9)\nNew York PEH February 2022 C 3\nFlorida College February – March 2022 B 3\nVirginia Statewide June 2022 – Present Y 36 (8)*\nIowa Community November 2022 – July 2023 W 12 (2)\nOhio Amish Community December 2023 – January 2024 B 6†\nColorado PEH Jan 2024 – Present Y 6*\nOklahoma Correctional Facility March 2024 – May 2024 C 2 (1)\nKingdom of Saudi Arabia Travel April 2024 – Present W§ 14*\nAbbreviation: MSM, men who have sex with men; PEH, people experiencing homelessness\n*Ongoing\n†5 additional suspect cases\n§One additional serogroup C case and one additional nongroupable caseSlide provided by Amy Rubis13\n14Is invasive meningococcal disease a problem of public health importance?Public Health Problem\nNo Probably \nnoProbably \nyesYes VariesDon’t \nknow\nPICO 1:  \nHealthy adolescents\n (0, 6 months)X\nPICO 2:\nPersons at increased risk \n(0, 1– 2, 6 months) X\nBenefits and harms\n- How substantial are the desirable anticipated effects?\n- How substantial are the undesirable anticipated effects?\n- Do the desirable effects outweigh the undesirable effects?\n16Comparators\n0, 6 month schedule 0, 2, 6 month schedule\nPICO 1 (healthy \nadolescents)Dose 2 Dose 2\nPICO 2 (persons at increased risk)-- Dose 3 vs. dose 2\nCD-6V72_72: Solicited AEs within 7 Days after Vaccination with \nMenB- 4C or MenACWYCRM\n0%20%40%60%80%100%%Participants*Solicited Local AEs Solicited Systemic AEs\nInjection-\nsite pain†Swelling‡Induration‡Erythema‡Fatigue†Headache†Myalgia†Arthralgia†Nausea† Fever§\nDose 1 2 1 2 1 2 1 2 1 2 1 2 1 2 1 2 1 2 1 2MenB -4C \n0,6m\nMenB -4C\n0,2,6m\nMenACWYCRM \n(1 dose)\n†Severity of symptom‡Size (mm)§Fever ( °C)\nMild – easily tolerated 25–50 38.0– 38.9\nModerate – interferes with normal activity 51–100 39.0– 39.9 \nSevere – prevents normal activity >100 ≥ 40.0\n Generally  mild-to-moderate  AE were reported following each vaccination\n Occurred at similar rates after the 1st, 2nd or 3rd dose of MenB -4C, and were higher than after vaccination with \nMenACWYCRM\n*Number of participants varies by study vaccination, 823- 835 for MenB -4C and 178 for MenACWY. \nAE: Adverse Event\nGSK, Data on File 2024N5550603 3 3 3 3 3 3 3 3 3\n17\n18How substantial are the desirable  anticipated effects?Benefits and Harms\nMinimal Small Moderate Large VariesDon’t \nknow\nPICO 1:  \nHealthy adolescents\n (0, 6 months)\nPICO 2:\nPersons at increased risk \n(0, 1– 2, 6 months) \n18\n19How substantial are the desirable  anticipated effects?Benefits and Harms\nMinimal Small Moderate Large VariesDon’t \nknow\nPICO 1:  \nHealthy adolescents\n (0, 6 months)\nPICO 2:\nPersons at increased risk \n(0, 1– 2, 6 months) \n19\n20How substantial are the desirable  anticipated effects?Benefits and Harms\nMinimal Small Moderate Large VariesDon’t \nknow\nPICO 1:  \nHealthy adolescents\n (0, 6 months)\nPICO 2:\nPersons at increased risk \n(0, 1– 2, 6 months) \n20\n21How substantial are the desirable  anticipated effects?Benefits and Harms\nMinimal Small Moderate Large VariesDon’t \nknow\nPICO 1:  \nHealthy adolescents\n (0, 6 months)\nPICO 2:\nPersons at increased risk \n(0, 1– 2, 6 months) \n21\n22How substantial are the desirable  anticipated effects?Benefits and Harms\nMinimal Small Moderate Large VariesDon’t \nknow\nPICO 1:  \nHealthy adolescents\n (0, 6 months)\nPICO 2:\nPersons at increased risk \n(0, 1– 2, 6 months) \n22\n23How substantial are the desirable  anticipated effects?Benefits and Harms\nMinimal Small Moderate Large VariesDon’t \nknow\nPICO 1:  \nHealthy adolescents\n (0, 6 months)X\nPICO 2:\nPersons at increased risk \n(0, 1– 2, 6 months) X X\n24How substantial are the undesirable  anticipated effects?Benefits and Harms\nMinimal Small Moderate Large VariesDon’t \nknow\nPICO 1:  \nHealthy adolescents\n (0, 6 months)X X\nPICO 2:\nPersons at increased risk \n(0, 1– 2, 6 months) X X\n25Do the desirable effects outweigh the undesirable effects?Benefits and Harms\nFavors \nnew \ndosing \nscheduleFavors \nprevious \ndosing \nscheduleFavors \nbothFavors \nneitherVariesDon’t \nknow\nPICO 1:  \nHealthy adolescents\n (0, 6 months)X X\nPICO 2:\nPersons at increased risk \n(0, 1– 2, 6 months) X\nValues\n- Does the target population feel that the desirable effects are large relative to \nthe undesirable effects?\n- Is there important uncertainty about or variability in how much people value \nthe main outcome?\nMenB  Coverage among Adolescents (2023)\n≥ 1 dose \namong 17 yr olds32.4%\n≥ 2 doses \namong 17 yr olds12.8%\nPingali  C et al. MMWR Morb  Mortal Wkly  Rep 2024. 27\n28Does the target population feel that the desirable effects are large relative to the \nundesirable effects? Values\nNo Probably \nnoProbably \nyesYes VariesDon’t \nknow\nPICO 1:  \nHealthy adolescents\n (0, 6 months)X\nPICO 2:\nPersons at increased risk \n(0, 1– 2, 6 months) X X\n29Is there important uncertainty about or variability in how much people value the \nmain outcome? Values\nImportant \nuncertainty \nor \nvariability Probably \nimportant \nuncertainty \nor variabilityProbably \nnot \nimportant \nuncertainty \nor variabilityNo \nimportant \nuncertainty \nor variabilityNo known \nundesirable \noutcomes\nPICO 1:  \nHealthy adolescents\n (0, 6 months)X\nPICO 2:\nPersons at increased risk \n(0, 1– 2, 6 months) X\nAcceptability\n- Is the intervention acceptable to key stakeholders?\n31Harmonized Schedules\nHarmonized dosing schedules for MenB- 4C (Bexsero) and \nMenB- FHbp (Trumenba ) would likely be viewed favorably by \nproviders  \n32Extended Dosing Intervals \nGeneral Best Practice Guidelines for Immunization. https://www.cdc.gov/vaccines/hcp/acip- recs/general -recs/index.html\nMeningococcal Vaccination: Recommendations of the Advisory Committee on Immunization Practices, United States, 2020 | MMWR (cdc. gov)   Doses administered at shorter- than -recommended intervals \ncan result in a sub- optimal immune response \n–However, extended intervals prolong the time until one achieves protection \nMay be challenging for patients needing to complete vaccine \nseries prior to complement inhibitor therapy initiation  \n–Persons using complement inhibitors should complete or update vaccination \nat least 2 weeks before complement inhibitor initiation unless the risks for delaying treatment outweigh the risks for developing meningococcal disease\n33Persons Taking Complement Inhibitors\nAmong unvaccinated persons for whom complement inhibitor \ntherapy cannot be delayed, antimicrobial prophylaxis should be \nadministered alongside meningococcal vaccination and \ncontinued for 2 weeks after vaccine administration\nPersons taking complement inhibitors likely remain at \nsubstantially increased risk for meningococcal disease, even if vaccinated and/or taking prophylaxis \nProviders could consider continued antimicrobial prophylaxis \nfor the duration of complement inhibitor treatment\n–Clinical judgement indicated\nMMWR - Meningococcal Vaccination: Recommendations of the Advisory Committee on Immunization Practices, United States, 2020 (cdc. gov)\n34Is the new dosing schedule acceptable to key stakeholders?Acceptability\nNo Probably \nnoProbably \nyesYes VariesDon’t \nknow\nPICO 1:  \nHealthy adolescents\n (0, 6 months)X\nPICO 2:\nPersons at increased risk \n(0, 1– 2, 6 months) X\nResource use\n- Is the intervention a reasonable and efficient allocation of resources?\n36Number of Doses \nNumber of doses remains the same for most healthy \nadolescents\n–Unless 2nd dose administered earlier than 6 months after \n1st dose\nAdditional dose required for at -risk populations\n37Dose Price\nPrice per Dose\nBexsero (MenB -4C) Trumenba  (MenB -FHbp)\nPrivate:  \n$223.746Private:  \n$190.26\nPublic pediatric:$150.026\nPublic adult:\n$128.352Public pediatric:$135.97\nPublic adult:\n$111.90 Harmonization with MenB- FHbp (Trumenba ) dosing \nschedule could increase pricing competition\nCurrent CDC Vaccine Price List | VFC Program | CDC\n38Is the new dosing schedule a reasonable and efficient allocation of resources?Resource Use\nNo Probably \nnoProbably \nyesYes VariesDon’t \nknow\nPICO 1:  \nHealthy adolescents\n (0, 6 months)X\nPICO 2:\nPersons at increased risk \n(0, 1– 2, 6 months) X\nEquity\n- What would be the impact on health equity?\n40Schedules that require extended intervals or additional visits \ncould disproportionately affect populations with lower access to health care\n–Unknown to what extent this would occurEquity\n41Proportion Completing Series by Age 17 Years:  \nNIS-TEEN (2022)\n%\nNon -VFC eligible\nMenB -4C (Bexsero) 49.6%\nMenB -FHbp  (Trumenba ) 35.5%\nVFC-eligible\nMenB -4C (Bexsero) 51.4%\nMenB -FHbp  (Trumenba ) 16.2%\n42Proportion Completing Series by Age 19 Years:  \nCommercial Claims (2017- 2023)\n%\nContinuously -enrolled\nMenB -4C (Bexsero) 67%\nMenB -FHbp  (Trumenba ) 60%\n43What would be the impact on health equityEquity\nReducedProbably \nreducedProbably \nno impactProbably \nincreasedIncreased VariesDon’t \nknow\nPICO 1:  \nHealthy adolescents\n (0, 6 months)X X\nPICO 2:\nPersons at increased risk \n(0, 1– 2, 6 months) X\nFeasibility\n- Is the intervention feasible to implement?\n45Providers may need to make adjustments to their \npractices (e.g., reminder/recall systems)\n–Especially for providers who administer MenB  vaccine just prior to \ncollege matriculation\nDifferent manufacturers’ MenB vaccine products remain \nnot interchangeableFeasibility\n46Is the new dosing schedule feasible to implement?  Feasibility\nNo Probably \nnoProbably \nyesYes VariesDon’t \nknow\nPICO 1:  \nHealthy adolescents\n (0, 6 months)X\nPICO 2:\nPersons at increased risk \n(0, 1– 2, 6 months) X\nSummary\n \n48EtR Domain QuestionPICO 1:  WG \nDeterminationPICO 2:  WG \nDetermination \nPublic health \nproblemIs IMD a problem of public health importance? Yes Yes\nBenefits and harmsHow substantial are the desirable anticipated effects? Small Small/moderate\nHow substantial are the undesirable anticipated effects Minimal/small Minimal/small\nDo the desirable anticipated effects outweigh the undesirable effects?Favors new schedule/favors bothFavors new schedule\nValues Does the target population feel the desirable effects are large relative to the undesirable effects?Don’t know Don’t know/ probably yes\nIs there important variability in how patients value the outcome?Probably not Probably not\nAcceptability Is the intervention acceptable to key stakeholders? Probably yes Probably yes\nResource use Is the intervention a reasonable allocation of resources? Probably yes Probably yes\nEquity What would be the impact of the intervention on health equity? Probably reduced/probably no impactProbably no impact\nFeasibility Is the intervention feasible to implement? Yes Yes\n49Balance of Consequences\nUndesirable \nconsequences \nclearly outweigh \ndesirable \nconsequences in \nmost settingsUndesirable \nconsequences \nprobably \noutweigh \ndesirable \nconsequences in \nmost settingsThe balance \nbetween \ndesirable and \nundesirable \nconsequences is \nclosely balanced \nor uncertainDesirable \nconsequences \nprobably \noutweigh \nundesirable \nconsequences \nin most settingsDesirable \nconsequences \nclearly \noutweigh \nundesirable \nconsequences \nin most \nsettingsThere is \ninsufficient \nevidence to \ndetermine the \nbalance of \nconsequences\nPICO 1:  \nHealthy adolescents\n (0, 6 months)X X X\nPICO 2:\nPersons at increased risk \n(0, 1– 2, 6 months) X X\n50Work Group Interpretation\nYes No\nPICO 1:  \nHealthy adolescents\n (0, 6 months)X\nPICO 2:\nPersons at increased risk \n(0, 1– 2, 6 months) XIs there sufficient information to move forward with a recommendation?\n51Work Group Interpretation\nPICO 1:\nShould MenB -4C be administered on a 0, 6 month dosing interval, vs. a 0, ≥1 month \ndosing interval, for the prevention of invasive meningococcal disease for persons \naged 16 –23 years recommended for MenB  vaccination based on shared clinical \ndecision -making?\nWe do not recommend the \ninterventionWe do recommend the \nintervention\nX\n52Work Group Interpretation\nPICO 2:\nShould MenB -4C be administered on a 0, 1 –2, 6 month schedule, vs. a 0, ≥1 month \nschedule, for the prevention of invasive meningococcal disease among persons with \npersistent complement component deficiencies, those with complement inhibitor \nuse, functional or anatomic asplenia, microbiologists routinely exposed to Neisseria meningitidis, or persons affected by an outbreak of serogroup B meningococcal disease?  \nWe do not recommend the \ninterventionWe do recommend the \nintervention\nX\n53Proposal Language\nACIP recommends MenB -4C (Bexsero) be administered as a 2 -dose \nseries at 0 and 6 months when given to healthy adolescents and young \nadults aged 16 –23 years based on shared clinical decision -making for the \nprevention of serogroup B meningococcal disease\nACIP recommends MenB -4C (Bexsero) be administered as a 3 -dose \nseries at 0, 1–2, and 6 months when given to persons aged ≥10 years at increased risk for serogroup B meningococcal disease (i.e., persons with \nanatomic or functional asplenia, complement component deficiencies, or \ncomplement inhibitor use; microbiologists routinely exposed to N. \nmeningitidis  isolates; and persons at increased risk during an outbreak)\nSummary and Work Group Considerations \nRegarding MenB -4C (Bexsero)\n Interval and Dosing Change\n55Summary\nProposed recommendations will align with updated FDA label for MenB -4C \n(Bexsero)\n–Harmonized with existing recommendations for MenB -FHbp (Trumenba )\nPros:\n•New dosing schedules associated with increased immunogenicity compared to \nprevious schedule\n•Harmonization between MenB -4C (Bexsero) and MenB -FHbp (Trumenba ) dosing \nintervals and schedules likely to be viewed favorably by providers (although vaccines from different manufacturers remain not interchangeable)\nCons:\n•Longer interval between doses increases the time to achieve vaccine- induced \nprotection and delays series completion\n•Persons receiving complement inhibitor therapy may need prolonged antimicrobial prophylaxis due to extended time for vaccine series completion  \n56Proposed MenB -4C (Bexsero) Recommendations\nHealthy adolescents and young adults (based on shared clinical decision-\nmaking):\n–2-dose series at 0 and 6 months \nPersons aged ≥10 years at increased risk for serogroup B meningococcal \ndisease (i.e., persons with anatomic or functional asplenia, complement \ncomponent deficiencies, or complement inhibitor use; microbiologists routinely exposed to N. meningitidis  isolates; and persons at increased risk during an \noutbreak):\n–3-dose series at 0, 1 –2, and 6 months\n57Proposal Language\nACIP recommends MenB -4C (Bexsero) be administered as a 2 -dose \nseries at 0 and 6 months when given to healthy adolescents and young \nadults aged 16 –23 years based on shared clinical decision -making for the \nprevention of serogroup B meningococcal disease\nACIP recommends MenB -4C (Bexsero) be administered as a 3 -dose \nseries at 0, 1–2, and 6 months when given to persons aged ≥10 years at increased risk for serogroup B meningococcal disease (i.e., persons with \nanatomic or functional asplenia, complement component deficiencies, or \ncomplement inhibitor use; microbiologists routinely exposed to N. \nmeningitidis  isolates; and persons at increased risk during an outbreak)\n58Proposed CDC Clinical Considerations\nNo recommendation to recall persons previously \nvaccinated at 0, ≥1 month \n–Healthy adolescents\n–Persons at increased risk\nPersons should continue with booster vaccination \nas previously recommended\n59Proposed CDC Clinical Considerations, cont.\nThe 3 -dose series (doses administered at 0, 1– 2, 6 \nmonths) may be used to optimize rapid protection for \nthose who initiate the vaccine series less than 6 months \nprior to period of increased risk\n–e.g., when series initiation occurs within 6 months of college \nmatriculation\nWould apply to MenB -4C (Bexsero) and MenB -FHbp \n(Trumenba )\n60CDC Clinical Considerations\n (currently recommended for MenB -FHbp [Trumenba ])\nWhen administering the 2 -dose series (e.g., for healthy adolescents):  \n–If the second dose is administered <6 months after the first dose, a third dose should \nbe administered ≥4 months after the second dose (as per label)\n–A second dose administered ≥6 months following the first dose is valid and does not need to be repeated  \nWhen administering the 3 -dose series (e.g., for persons at increased risk):  \n–A third dose is not needed if the second dose was administered ≥6 months after the \nfirst dose  \n–If the third dose is administered <4 months after the second dose and <6 months \nafter the first dose, the dose should be repeated ≥ 4 months after the last dose  \n61Clinical Considerations, cont. (Unchanged)\nMenB  vaccines from different manufacturers are not interchangeable\n–All doses in a series, as well as booster doses, should be from the same manufacturer.  \n–If doses from both manufacturers have been administered to the same patient, the \npatient should receive a complete series of either manufacturers’ product without counting doses of the other manufacturer as valid. \nMenB -4C (Bexsero) may be administered simultaneously with other \nvaccines\n–MenB  vaccine should be administered in a separate limb from other vaccines \nadministered on the same clinic day, if feasible.\nContraindications:  Severe allergy to prior dose or component of vaccine \nPrecautions:  Pregnancy, moderate or severe acute illness \n62Acknowledgements\nLucy McNamara\nAmy Rubis\nGabrielle Cooper\nCheryl Isenhour\nLeAnne Fox\nSusan Hariri\nNoele Nelson\nThank you!\n63For more information, contact CDC\n1-800- CDC- INFO (232- 4636)\nTTY:  1 -888- 232- 6348    cdc.gov\nFollow us on X (Twitter) @CDCgov & @CDCEnvironment\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position o f \nthe U. S. Centers for Disease Control and Prevention.", "summary": "Introduction to MenB -4C (Bexsero) Interval and Dosing  Label Change Sarah F. Schillie, MD, MPH, MBA Advisory Committee on Immunization Practices October 24, 2024National Center for Immunization & Respiratory Diseases 1 2MenB -4C (Bexsero) Interval Changes Initially licensed by FDA under an accelerated approval  process New immunogenicity data support changes to dosing schedule  –No safety concerns Full FDA approval:  August 19, 2024 New dosing schedule aligned with MenB- FHbp  …", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-23-24-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/04-mening-Schillie-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 63}
{"title": "01 RSV Adult Shaw 508", "content": "RSV Vaccination in Adults:\nIntroduction\nAlbert Shaw, MD, PhD\nChair, Adult RSV Work Group\nAdvisory Committee on Immunization Practices\nOctober 24, 2024National Center for Immunization and Respiratory Diseases\n2Adult RSV Work Group Membership\nACIP Voting Members\nAlbert Shaw (Chair)\nHelen Chu\nMini Kamboj\nKeipp Talbot \nEx Officio Members\nNicholas Geagan (FDA)\nNadine Peart Akindele (FDA)\nRachel Zhang (FDA) \nMichelle Juaneza (HRSA)\nUzo Chukwuma (IHS)\nSonnie Kim (NIH/NIAID)CDC Co -Leads\nAmadea Britton\nMichael MelgarConsultants\nRobert Atmar (Baylor College of Medicine)\nDoug Campos -Outcalt (University of Arizona)\nPeter Donofrio (Vanderbilt University)\nMarie Griffin (Vanderbilt University)\nCamille Kotton (Massachusetts General Hospital)\nCynthia Lucero (Veterans Health Administration)\nRebecca Morgan (Case Western Reserve University)\nTracy Ruckwardt (NIH/NIAID)\nJonathan Temte  (University of Wisconsin)Liaisons\nBindy Crouch (AIM)\nApril Killikelly (NACI, PHAC)\nGretchen LaSalle (AAFP)\nRuth Lynfield (NFID) \nSteven Pergam (IDSA)\nKenneth Schmader (AGS)\nWinnie Siu (NACI, PHAC)\nElizabeth Skoy ( APhA )\nVidya Sundareshan (ACP)\nKatherine Williams (APTR) \n3CDC Contributors\nMelissa Coughlin\nFatima Dawood\nKatherine Fleming -Dutra\nJarrett Gartin\nMonica Godfrey\nAron Hall\nFiona Havers\nSuzanne Heitfield\nMichele Hlavsa\nJefferson Jones\nRuth Link -Gelles\nAgustin Lopez\nJosephine Mak\nMeredith McMorrowNoelle -Angelique Molinari\nDanielle Moulia\nIsmael Ortega -Sanchez\nLakshmi Panagiotakopoulos\nPragna Patel\nMonica Patton\nAmanda Payne\nMila Prill\nLauren Roper\nMelisa Shah\nDiya Surie\nNatalie Thornburg\nDennis Wang\nTrang WisardImmunization Safety Office\nTarayn Fairlie\nJulianne Gee\nAnne Hause\nMichael McNeil\nPedro Moro\nChristine Olson\nDavid Shay\nJohn Su\nEric WeintraubImmunization Services Division\nErin Abramsohn\nJanelle King\nAndrew Leidner\nAmy Parker Fiebelkorn\nJamison Pike\nInfluenza Division\nJill Ferdinands\nLisa GrohskopfNCIRD Office of the Director\nJessica MacNeil\nHannah Rosenblum\nMelinda WhartonCoronavirus and Other Respiratory Viruses Division \n4June 2024  ACIP Recommendations for RSV Vaccination \nin Older Adults:\nACIP recommends all adults aged ≥75 years and adults aged 60 –74 years \nwho are at increased risk of severe RSV disease receive a single dose of RSV \nvaccine.1,2\n1. Recommendation is for any Food and Drug Administration –approved RSV vaccine ( Arexvy  [GSK]; \nAbrysvo  [Pfizer]; or mResvia  [Moderna]). There is no product preference. \n2. Eligible adults are currently recommended to receive a single dose of RSV vaccine; adults who have \nalready received RSV vaccination should not receive another dose.\nhttps://www.cdc.gov/mmwr/volumes/73/wr/mm7332e1.htm?s_cid=mm7332e1_w  \n5•Protein subunit (based on RSV F protein in prefusion conformation)\n-GSK Arexvy1: monovalent RSV -A, AS01E adjuvant\n-Pfizer Abrysvo2: bivalent RSV -A/RSV -B, no adjuvant\n•Messenger RNA (mRNA, encoding RSV F protein in prefusion conformation)\n-Moderna mResvia3: monovalent RSV -A, no adjuvantCurrent FDA -approved RSV vaccines\n1. https://www.fda.gov/media/167805/download\n2. https://www.fda.gov/media/168889/download\n3. https://www.fda.gov/media/179005/download\n6•Protein subunit\n-GSK Arexvy1: monovalent RSV -A, AS01E adjuvant\n-Pfizer Abrysvo2: bivalent RSV -A/RSV -B, no adjuvant\n•mRNA\n-Moderna mResvia3: monovalent RSV -A, no adjuvantCurrent FDA -approved RSV vaccines\nApproved for prevention of \nlower respiratory tract \ndisease (LRTD) caused by RSV \nin adults aged ≥60 years\n1. https://www.fda.gov/media/167805/download\n2. https://www.fda.gov/media/168889/download\n3. https://www.fda.gov/media/179005/download\n7•Protein subunit\n-GSK Arexvy1: monovalent RSV -A, AS01E adjuvant\n-Pfizer Abrysvo2: bivalent RSV -A/RSV -B, no adjuvant\n•mRNA\n-Moderna mResvia3: monovalent RSV -A, no adjuvantCurrent FDA -approved RSV vaccines\nAlso approved for prevention \nof LRTD caused by RSV in \nadults aged 50 –59 years \nwho are at increased risk for \nLRTD caused by RSV*\n*There is no current ACIP \nrecommendation for RSV vaccination in \nnon-pregnant adults aged <60 years.1. https://www.fda.gov/media/167805/download\n2. https://www.fda.gov/media/168889/download\n3. https://www.fda.gov/media/179005/download\n8•Protein subunit\n-GSK Arexvy1: monovalent RSV -A, AS01E adjuvant\n-Pfizer Abrysvo2: bivalent RSV -A/RSV -B, no adjuvant\n•mRNA\n-Moderna mResvia3: monovalent RSV -A, no adjuvantCurrent FDA -approved RSV vaccines\nAlso approved and \nrecommended for active \nimmunization of pregnant \nindividuals of any age* at \n32–36 weeks gestational age \nfor the prevention of LRTD \nand severe LRTD caused by \nRSV in infants from birth \nthrough 6 months of age.\n1. https://www.fda.gov/media/167805/download\n2. https://www.fda.gov/media/168889/download\n3. https://www.fda.gov/media/179005/download*There is no current ACIP \nrecommendation for RSV vaccination in \nnon-pregnant  adults aged <60 years.\n9•Protein subunit\n-GSK Arexvy1: monovalent RSV -A, AS01E adjuvant\n-Pfizer Abrysvo2: bivalent RSV -A/RSV -B, no adjuvant\n•mRNA\n-Moderna mResvia3: monovalent RSV -A, no adjuvantCurrent FDA -approved RSV vaccines\nAs of 10/22/244: also \napproved for prevention of \nLRTD caused by RSV in adults \naged 18 –59 years who are at \nincreased risk for LRTD \ncaused by RSV*\n1. https://www.fda.gov/media/167805/download\n2. https://www.fda.gov/media/168889/download\n3. https://www.fda.gov/media/179005/download\n4. https://www.pfizer.com/news/press -release/press -release -detail/us -fda-approves -pfizers -rsv-vaccine -abrysvor -adults -aged -18*There is no current ACIP \nrecommendation for RSV vaccination in \nnon-pregnant  adults aged <60 years.\n10•No vote at today’s meeting\n•Since June, the Work Group has been reviewing updated data relevant \nto current recommendations and discussing potential policy options for \nan RSV vaccination recommendation in adults aged <60 years\n•Today, ACIP will see presentations from FDA, as well as manufacturer \npresentations with updates on co -administration, duration of protection, \nand immunogenicity in adults with immune compromise\n•The Work Group will share interpretations regarding these updates and \nconsiderations for future policy Today’s meeting\n11Agenda: Thursday October 24, 2024\n•Manufacturer presentation: mResvia  (Moderna) coadministration \nwith high -dose influenza vaccine\n•Manufacturer presentation: Abrysvo  (Pfizer) immunogenicity in \nimmunocompromised adults and coadministration with COVID -19 \nand influenza vaccines\n•Manufacturer presentation: Arexvy  (GSK) season 3 update on \nsafety, efficacy and immunogenicity in solid organ transplant \nrecipients\n•Evaluation of Guillain -Barré Syndrome (GBS) following protein \nsubunit RSV vaccination among adults 65 years and older  \n \n•Work Group interpretations  \n \n•ACIP open discussion and questions  •Dr. Rituparna Das (Moderna)\n•Dr. Iona Munjal (Pfizer)\n•Dr. Susan Gerber (GSK)\n•Dr. Patricia Lloyd (FDA)\n•Dr. Michael Melgar (CDC)\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position \nof the Centers for Disease Control and Prevention.", "summary": "RSV Vaccination in Adults: Introduction Albert Shaw, MD, PhD Chair, Adult RSV Work Group Advisory Committee on Immunization Practices October 24, 2024National Center for Immunization and Respiratory Diseases 2Adult RSV Work Group Membership ACIP Voting Members Albert Shaw (Chair) Helen Chu Mini Kamboj Keipp Talbot  Ex Officio Members Nicholas Geagan (FDA) Nadine Peart Akindele (FDA) Rachel Zhang (FDA)  Michelle Juaneza (HRSA) Uzo Chukwuma (IHS) Sonnie Kim (NIH/NIAID)CDC Co -Leads Amadea…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-23-24-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/01-RSV-Adult-Shaw-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 12}
{"title": "02 RSV Adult Das 508", "content": "© 2024 Moderna, inc. All rights reserved.RSV Vaccine ( mRESVIA , mRNA -1345) \nConcomitant Administration Overview\nAdvisory Committee on Immunization Practices\nRituparna Das, MD PhD \nOct 24, 2024\n1\n© 2024 Moderna, inc. All rights reserved.\nCumulative Burden of Seasonal Respiratory Viruses in US Older Adults\nRSV Influenza2\nCumulative US \nHospitalization Rate \n(≥65 yr, rate/100,000, 9/28/2024)1 227 106\nUS Vaccine Coverage \n2023 -242-4\n(COVID -19 & Flu ≥65 yrs, RSV ≥60 yrs)70% 23%\n1.CDC RESP -NET, MMWR week 39, week ending 9/28/2024, https://www.cdc.gov/resp -net/dashboard/index.html  accessed 10/18/2024 ; 2. CDC COVIDVaxView \nhttps://www.cdc.gov/covidvaxview/  ; 3. CDC FluVaxView  https://www.cdc.gov/covidvaxview/  ; 4. CDC RSVVaxView https://www.cdc.gov/rsvvaxview/  5. Bonanni et al \nHuman Vaccines Immuno 2023; 6. NVAC Pediatrics. 2003;. 7. https://www.cdc.gov/vaccines/hcp/acip -recs/general -recs/timing.html#ref -13; 8. Britton et al. MMWR 2024 \nhttps://www.cdc.gov/mmwr/volumes/73/wr/mm7332e1.htmCOVID -19\n811\n39%\nConcomitant administration of vaccines is an effective method to increase vaccine coverage.\nMMWR: Coadministration of RSV vaccines with other adult vaccines during the same visit is \nacceptable5-8 \n© 2024 Moderna, inc. All rights reserved.\nmRNA 1345 Clinical Development\nNCT05127434, NCT05330975, NCT060604573\nAdults ≥60 years\nStudy 301\nEfficacy, Immunogenicity, Safety, and Correlate of Protection\nConcomitant Administration \nwith Standard Dose Influenza\nAdults ≥50 years\nStudy 302 - Part B\nConcomitant Administration \nwith COVID -19\nAdults ≥65 years\nStudy 304\nConcomitant Administration \nwith High Dose Influenza\nAdults ≥50 years\nStudy 302 - Part A\n© 2024 Moderna, inc. All rights reserved.\nSummary of Today’s Presentation4\n1. ACIP, Feb 2024 Study 302 Parts A & B – Supports coadministration of mRNA -1345 with standard dose influenza and \nCOVID -19 vaccines (previously presented)1\n•Well tolerated with no safety concerns\n•Robust immunogenicity observed for all influenza strains, COVID -19, and RSV\nStudy 304 – Data for coadministration of mRNA -1345 with high -dose influenza vaccine \n•Well-tolerated with no safety concerns\n•Robust immunogenicity observed for all influenza strains and RSV\n•RSV titers lower with coadministration; data from correlate of protection model demonstrate \nthat clinical efficacy against RSV disease, including severe disease, is likely maintained\nOverall, the benefit: risk of coadministration of mRNA -1345 with standard and high -dose influenza \nvaccines, and COVID -19 vaccine is positive \n© 2024 Moderna, inc. All rights reserved.\nRSV Case Accrual and Efficacy Analyses through 3 Seasons \nin the Phase 2/3 Pivotal Trial\nStudy 3015\n012345678910\n1. CDC. Respiratory Syncytial Virus Hospitalization Surveillance Network (RSV -NET). https://www.cdc.gov/respiratory -viruses/data -research/dashboard/most -\nimpacted -hospitalizations.html  2. Based  on final FDA Package InsertOverall US \n2021 -2023 RSV \nHospitalization \nRate per \n100,000 Adults \n≥ 65 Years1 \n2021 -2022 \nRSV Season 1Durability through \nSeason 2\nNov ‘21 – Apr ‘23Primary Analysis\nNov ‘21 – Nov ’22 \n2022 -2023 \nRSV Season 2Durability through \nSeason 3 \nNov ‘21 – Mar ‘24\n2023 -2024 \nRSV Season 3\n2021 2022 2023 2024LRTD 2+ \nCases \n85 78.7%\n174Efficacy2\n50.3%\n(37.5%, 60.7%)56.7%\n33.1%, 72.6%)LRTD 2+Severe RSV \n(shortness of \nbreath)\n62.5%\n(47.7%, 73.1%)74.6%\n(50.7%, 86.9%)78.7%\n(62.8%, 87.9%)86.7%\n(41.9%, 97.0%)\n338\n© 2024 Moderna, inc. All rights reserved.\nPredicted Efficacy\n•Coadministration efficacy\n•Revaccination efficacy\nINPUT from Phase 3 Pivotal Efficacy Trial \n(Study 301)RSV Correlate of Protection Model\nPreplanned case -cohort design6\n1597 \nmRNA -1345 \nRecipients\n533 \nPlacebo \nRecipients\n271 \nRSV ARD \nCases1\nOUTPUT\n•Day 1 and Day 29 sera collected from all study participants \n•Evaluated for RSV -A and B neutralizing titers, and Pre -F binding titers\n•Objective to determine the relationship between immunogenicity and efficacy to identify \ncorrelates of protection\n1.Includes 174 LRTD2+ and 70 LRTD3+ RSV cases; Ma, C et al, RSVVW, 2024\n© 2024 Moderna, inc. All rights reserved.\nCorrelate of Risk Antibodies are a Correlate of Risk and Correlate of \nProtection for RSV\nStudy 301 – LRTD2+ RSV Efficacy7\nThe panels demonstrate the Correlate of Risk  (A) and Correlate of Protection (B) analysis for the RSV -LRTD 2+ endpoint by Day 29 RSV -A neutralizing antibody.\nA.The red and blue solid curves demonstrate the point estimate of the predictive risk for vaccine and placebo recipients at eac h assigned antibody titer. The red and blue dashed curves along with the \nshaded area represent the bootstrap point -wise 95% confidence interval (CI). \nB.The solid black curve shows the point estimate of controlled vaccine efficacy at each assigned antibody titer and the dashed curves demonstrate the bootstrap point -wise 95% CI. \n102 103 104 105\nDay 29 RSV -A Neutralizing Antibody Titer \n(IU/mL)Probability \nof RSV0.035\n0.030\n0.025\n0.020\n0.010\n0.0050.015RSV-A Neutralizing Antibody\nmRNA -1345 50 g\nPlaceboCorrelate of Protection \n102 103104 105\nDay 29 RSV -A Neutralizing Antibody Titer \n(IU/mL)Estimated \nVaccine \nEfficacy1.0\n0.8\n0.6\n0.2\n00.4\n© 2024 Moderna, inc. All rights reserved.\nConcomitant Administration \nof mRNA -1345 with High -Dose  \nInfluenza Vaccine\nStudy 3048\n© 2024 Moderna, inc. All rights reserved.\nStudy Design – Concomitant Administration of \nmRNA -1345 & Fluzone HD\nStudy 304 - Phase 3, Randomized, Observer -Blind Trial\nUnited States\nDay 22Day 1\nStratified by age: 65–74 and ≥75 years (20%)\nStudy duration: ~8 months per participantFluzone HD + \nmRNA -1345 Fluzone HD + \nPlacebo\nPlacebo mRNA -1345Vaccine \nRegimenGroup 2\n(Sequential administration)1:1 Randomization\n~1900 adults ≥65 years of age \nGroup 1\n(Concomitant administration)9\n© 2024 Moderna, inc. All rights reserved.\n110100100010000100000\nBaseline Day 22 Baseline Day 22Concomitant Administration Results in Robust RSV and \nInfluenza Responses Across All Adults ≥65 Years \nStudy 304\nGMT; Geometric Mean TiterGroup 1\nD1: Flu HD + mRNA -1345\nD22: PlaceboGroup 2\nD1: Flu HD + Placebo\nD22: mRNA -1345\nGroup 1 Group 2GMT\n(95% CI)10\nRSV-A Neutralizing Antibody Influenza A/H3N2, HAI\n1101001000\nBaseline Day 22 Baseline Day 22\nGroup 1 Group 2\n© 2024 Moderna, inc. All rights reserved.\nCo-Primary Immunogenicity Endpoint Evaluation\nGMR  (95% CI)\nInfluenza A/H1N1 0.87 (0.78, 0.98)\nInfluenza A/H3N2 0.87 (0.78, 0.97)\nInfluenza B/Austria 0.89 (0.81, 0.98)\nInfluenza B/Phuket 0.95 (0.87, 1.03)\nRSV-A 0.63 (0.57, 0.69)\nRSV-B 0.64 (0.58, 0.70)Study 304\n0 0.2 0.4 0.6 0.8 1 1.2\nGMR (95% CI)11\nGMR for all influenza strains close to 1; RSV GMRs lower, potential for clinical impact on efficacy will\n be discussed\n© 2024 Moderna, inc. All rights reserved.\nCorrelation of Protection Suggests RSV Vaccine Efficacy Maintained \nwith Concomitant Administration of mRNA -1345 and Fluzone HD\nStudy 304  – Adults ≥65 Years\nNo statistical difference in predicted vaccine efficacy; point estimates were similarAntibody Treatment Group1 Day 22 GMT RSV-LRTD 2+ RSV-LRTD 3+\nRSV-A \n(IU/mL)Coadministration 11,57070% \n(54, 84)86% \n(70, 96)\nSequential Administration 19,20377%\n(64, 87)88%\n(75, 97)\nRSV-B\n(IU/mL)Coadministration 4,03669%\n(51, 83)86%\n(69, 97)\nSequential Administration 6,87673%\n(58, 85)88%\n(73, 97)\n1. Concomitant administration: Fluzone  HD + mRNA -1345 at Day 1;  Sequential Administration: Fluzone  HD + placebo at Day 1,  mRNA -1345 at Day 22\nCorrelate of protection model based on ≥ 65 yr olds in study 301 to be consistent with age of study 304 participants 0% 20% 40% 60% 80% 100% 0% 20% 40% 60% 80% 100%\nPredicted Vaccine Efficacy \n(95% CI)Predicted Vaccine Efficacy \n(95% CI)12\n© 2024 Moderna, inc. All rights reserved.\nConcomitant Administration of mRNA -1345 and Fluzone HD \nWell Tolerated with No Safety Concerns Identified \n•Concomitant administration well tolerated\n•Predominantly mild events\n•1-3 days duration\n•Reassuring safety profile:\n•No Guillain -Barre Syndrome (GBS)\n•No acute disseminated encephalomyelitis (ADEM)\n•No anaphylaxis\n•No thrombocytopenia\n•No cases of acute myocarditis or acute pericarditis Study 304\nCEAC – Cardiac Event Adjudication Committee13\n© 2024 Moderna, inc. All rights reserved.\nConcomitant Administration of \nmRNA -1345 with Standard Dose \nInfluenza and COVID -19 \nVaccines\nStudy 302, Parts A & B14\n© 2024 Moderna, inc. All rights reserved.\nAntibody GMR (95% CI)\nInfluenza A/H1N1 0.89 (0.77, 1.03)\nInfluenza A/H3N2 0.97 (0.86, 1.09)\nInfluenza B/Phuket 0.91 (0.81, 1.02)\nInfluenza B/Washington 0.93 (0.82, 1.05)\nRSV-A Neutralizing  0.81 (0.67, 0.97)\nRSV-B Neutralizing 0.85 (0.73, 1.00)Comparable Immunogenicity with Concomitant vs Nonconcomitant  \nAdministration of mRNA -1345 and Standard Dose Influenza  Vaccine\nStudy 302, Part A\n0 0.2 0.4 0.6 0.8 1 1.2\nGMR  (95% CI)15\n© 2024 Moderna, inc. All rights reserved.\nComparable Immunogenicity with Concomitant vs Nonconcomitant  \nAdministration of mRNA -1345 and COVID -19 Bivalent Vaccine\nStudy 302, Part B\nAntibody GMR (95% CI)\nCOVID -19 (Wuhan) 0.96 (0.87, 1.06)\nCOVID -19 (Omicron) 1.00 (0.89, 1.14)\nRSV-A Neutralizing  0.80 (0.70, 0.90)\nRSV-B Neutralizing  0.89 (0.79, 1.00)\n0 0.2 0.4 0.6 0.8 1 1.2\nGMR  (95% CI)16\n© 2024 Moderna, inc. All rights reserved.\nSummary17\n© 2024 Moderna, inc. All rights reserved.\nSummary of Today’s Presentation18\n1. ACIP, Feb 2024 Study 302 Parts A & B – Supports coadministration of mRNA -1345 with standard dose influenza and \nCOVID -19 vaccines (previously presented)1\n•Well tolerated with no safety concerns\n•Robust immunogenicity observed for all influenza strains, COVID -19, and RSV\nStudy 304 – Data for coadministration of mRNA -1345 with high -dose influenza vaccine \n•Well-tolerated with no safety concerns\n•Robust immunogenicity observed for all influenza strains and RSV\n•RSV titers lower with coadministration; data from correlate of protection model demonstrate \nthat clinical efficacy against RSV disease, including severe disease, is likely maintained\nOverall, the benefit: risk of coadministration of mRNA -1345 with standard and high -dose influenza \nvaccines, and COVID -19 vaccine is positive \nThank you\n© 2024 Moderna, inc. All rights reserved.19•Investigators\n•Study site personnel\n•Laboratory personnel\n•Most importantly, the individuals who participated in these trials19", "summary": "© 2024 Moderna, inc. All rights reserved.RSV Vaccine ( mRESVIA , mRNA -1345)  Concomitant Administration Overview Advisory Committee on Immunization Practices Rituparna Das, MD PhD  Oct 24, 2024 1 © 2024 Moderna, inc. All rights reserved. Cumulative Burden of Seasonal Respiratory Viruses in US Older Adults RSV Influenza2 Cumulative US  Hospitalization Rate  (≥65 yr, rate/100,000, 9/28/2024)1 227 106 US Vaccine Coverage  2023 -242-4 (COVID -19 & Flu ≥65 yrs, RSV ≥60 yrs)70% 23% 1.CDC RESP -NET,…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-23-24-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/02-RSV-Adult-Das-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 19}
{"title": "03 RSV Adult Munjal 508", "content": "ACIP Presentation October 24, 2024\nIona Munjal, MD, FAAP\nClinical Research and \nDevelopment,\nPfizer Vaccines\nBivalent Stabilized Prefusion F\nRSV A and RSV B strains\nAdult\nActive immunization for the prevention of LRTD \ncaused by RSV in individuals 60 years of age and \nolder.Maternal\nActive immunization of pregnant individuals at 32 \nthrough 36 weeks gestational age for the \nprevention of lower respiratory tract disease \n(LRTD) and severe LRTD caused by respiratory \nsyncytial virus (RSV) in infants from birth through \n6 months of age.\n2\nKPSC, Kaiser Permanente Southern California; IC, Immunocompromised; HR, High Risk•Revaccination through 5 RSV \nseasons•Chronic \nmedical \nconditions\n•Non -\ninferiority \ndemonstrated •Immuno - \ncompromising \nand High Risk \nconditions \n•Efficacy \nthrough 2 \nseasons•Efficacy  \n(including IC \nand HR)•Non -\ninferiority \ndemonstrated•Non -\ninferiority \ndemonstrated\nOngoing Ongoing\nImmunocompromised, or renal, \nor hepatic impaired in EUGuillain -Barré Syndrome in US Atrial Fibrillation in US among \nVA patientsNear Real -time Guillain -Barré \nSyndrome in US\nAdults ≥ 60Adults \n18–59 Adults ≥ 18 Adults ≥ 65 Adults ≥ 65 Adults ≥ 60\n3\nKPSC, Kaiser Permanente Southern California; IC, Immunocompromised; HR, High Risk•Revaccination through 5 RSV \nseasons•Chronic \nmedical \nconditions\n•Non -\ninferiority \ndemonstrated •Immuno - \ncompromising \nand High Risk \nconditions \n•Efficacy \nthrough 2 \nseasons•Efficacy  \n(including \nImmunocomp\nromised and \nHigh Risk)•Non -\ninferiority \ndemonstrated•Non -\ninferiority \ndemonstrated\nOngoing Ongoing\nImmunocompromised, or renal, \nor hepatic impaired in EUGuillain -Barré Syndrome in US Atrial Fibrillation in US among \nVA patientsNear Real -time Guillain -Barré \nSyndrome in US\nAdults ≥ 60Adults \n18–59 Adults ≥ 18 Adults ≥ 65 Adults ≥ 65 Adults ≥ 60\n4\n1. Belongia  EA, King JP , Kieke  BA, et al. Clinical features, severity, and incidence of RSV illness during 12 consecutive seasons in a community cohort of a dults ≥60 years old. Open Forum Infect Dis.  2018;5(12): ofy316 .\n2. Wyffels  V, Kariburyo  F , Gavart  S, et al. A real -world analysis of patient characteristics and predictors of hospitalization among US Medicare beneficiaries wi th respiratory syncytial virus infection. Adv Ther . 2020;37(3):1203 -17.\n3.Rates of Lower Respiratory T ract Illness in US Adults by Age and Comorbidity Profile | Infectious Diseases and Therapy (sprin ger.com) .\n5Incidence rate and risk for severe complications from RSV infection (hospitalization,\nmortality, etc.) are higher among immunocompromised adults and those with at risk  \nconditions1,2,3\n\nAbbreviations: AE, adverse event; AESIs, adverse event of special interest; NDCMC, newly diagnosed chronic medical condition;  SAE, serious adverse event.\nClinicaltrials.gov NCT05842967\nImmunocompromised \nadults aged ≥18 years \nRSVpreF\ndose 1\nVaccine \nadministration IMBlood draw for \nimmunogenicityPhase 3, single -arm, \nopen -label, multicenter, \ndescriptive study\n200 immunocompromised \nparticipants aged ≥18 years\n(~half aged ≥60 years)\n11 sites in the USA\nMay 2023 – March 2024 RSVpreF\ndose 2\ne\nReactogenicity \ne-diarye\ne\n6\n\nNon -small cell lung cancer participants on per protocol therapy\nSolid organ transplant recipients at least 3 months prior to enrollment\nIncluding : \n•Kidney (19%) •Lung (10%) •Liver (7%)\nParticipants with autoimmune inflammatory disorders  on active \nimmuno -modulator therapy\nIncluding : \n•Rheumatoid arthritis \n•Systemic lupus erythematosus (SLE)\n•Sjogren’s syndrome•Ulcerative colitis/Crohn’s disease\n•Psoriasis/psoriatic arthritis\n•Multiple sclerosis\nParticipants on hemodialysis  due to ESRD•Heart (2%)\n7\nSex n (z%) n (%) n (%)\nFemale 56 (58.3) 53 (49.5) 109 (53.7)\nRace\nWhite 63 (65.6) 87 (81.3) 150 (73.9)\nAsian 6 (6.3) 2 (1.9) 8 (3.9)\nAmerican Indian \nor Alaska Native1 (1.0) 3 (2.8) 4 (2.0)\nBlack or African \nAmerican25 (26.0) 15 (14.0) 40 (19.7)\nEthnicity\nNon -Hispanic/\nnon -Latino88 (91.7) 101 (94.4) 189 (93.1)\nHispanic/Latino 8 (8.3) 3 (2.8) 11 (5.4)\nAge at Dose 1 \nMedian (min, max) 51 (23, 59) 66 (60, 80) 60 (23, 80)\nImmunocompromised and High Risk Conditions\nSolid Organ Transplant 32 (33.3) 43 (40.2) 75 (36.9)\nAutoimmune \nInflammatory Disorders \non Immunomodulator \nTherapy44 (45.8) 53 (49.5) 97 (47.8)\nAdvanced NSCLC on \nTherapy3 (3.1) 2 (1.9) 5 (2.5)\nESRD on Hemodialysis 20 (20.8) 11 (10.3) 31 (15.3)\n8\nSex n (z%) n (%) n (%)\nFemale 56 (58.3) 53 (49.5) 109 (53.7)\nRace\nWhite 63 (65.6) 87 (81.3) 150 (73.9)\nAsian 6 (6.3) 2 (1.9) 8 (3.9)\nAmerican Indian \nor Alaska Native1 (1.0) 3 (2.8) 4 (2.0)\nBlack or African \nAmerican25 (26.0) 15 (14.0) 40 (19.7)\nEthnicity\nNon -Hispanic/\nnon -Latino88 (91.7) 101 (94.4) 189 (93.1)\nHispanic/Latino 8 (8.3) 3 (2.8) 11 (5.4)\nAge at Dose 1 \nMedian (min, max) 51 (23, 59) 66 (60, 80) 60 (23, 80)\nImmunocompromised and High Risk Conditions\nSolid Organ Transplant 32 (33.3) 43 (40.2) 75 (36.9)\nAutoimmune \nInflammatory Disorders \non Immunomodulator \nTherapy44 (45.8) 53 (49.5) 97 (47.8)\nAdvanced NSCLC on \nTherapy3 (3.1) 2 (1.9) 5 (2.5)\nESRD on Hemodialysis 20 (20.8) 11 (10.3) 31 (15.3)\n9\nSex n (z%) n (%) n (%)\nFemale 56 (58.3) 53 (49.5) 109 (53.7)\nRace\nWhite 63 (65.6) 87 (81.3) 150 (73.9)\nAsian 6 (6.3) 2 (1.9) 8 (3.9)\nAmerican Indian \nor Alaska Native1 (1.0) 3 (2.8) 4 (2.0)\nBlack or African \nAmerican25 (26.0) 15 (14.0) 40 (19.7)\nEthnicity\nNon -Hispanic/\nnon -Latino88 (91.7) 101 (94.4) 189 (93.1)\nHispanic/Latino 8 (8.3) 3 (2.8) 11 (5.4)\nAge at Dose 1 \nMedian (min, max) 51 (23, 59) 66 (60, 80) 60 (23, 80)\nImmunocompromised and High Risk Conditions\nSolid Organ Transplant 32 (33.3) 43 (40.2) 75 (36.9)\nAutoimmune \nInflammatory Disorders \non Immunomodulator \nTherapy44 (45.8) 53 (49.5) 97 (47.8)\nAdvanced NSCLC on \nTherapy3 (3.1) 2 (1.9) 5 (2.5)\nESRD on Hemodialysis 20 (20.8) 11 (10.3) 31 (15.3)\n10\nAbbreviations: GMFR = geometric mean fold rise; GMT = geometric mean titer; NA = not applicable; RSV = respiratory syncytial virus.\n11\n1001,00010,000100,000\nRSV A RSV BRSV 50% Neutralizing GMTsBefore Dose 1 1 Month after Dose 1 1 Month after Dose 2\n8.3 7.5 9.0 7.8\n\nAbbreviations: GMFR = geometric mean fold rise; GMT = geometric mean titer; NA = not applicable; RSV = respiratory syncytial virus.\n12RSV A\n6.4 7.2 8.6 6.4 21.0  18.8  13.8  12.5\n1001,00010,000100,000\nSolid Organ Transplant\n(n=67)Autoimmune Inflammatory Disorders\n(n=94)Non -Small Cell Lung Cancer\n(n=3)End Stage Renal Disease on \nHemodialysis (n=28)RSV 50% Neutralizing GMTsBefore Dose 1 1 Month after Dose 1 1 Month after Dose 2\nAbbreviations: GMFR = geometric mean fold rise; GMT = geometric mean titer; NA = not applicable; RSV = respiratory syncytial virus.\n13RSV B\n6.7 7.4 9.5 6.9 28.0  19.5  14.6  12.7\n1001,00010,000100,000\nSolid Organ Transplant\n(n=67)Autoimmune Inflammatory Disorders\n(n=94)Non -Small Cell Lung Cancer\n(n=3)End Stage Renal Disease on Hemodialysis \n(n=28)RSV 50% Neutralizing GMTsBefore Dose 1 1 Month after Dose 1 1 Month after Dose 2\nAbbreviations: GMFR = geometric mean fold rise; GMT = geometric mean titer; NA = not applicable; RSV = respiratory syncytial virus; HR: High -risk; IC: Immunocompromised; PD1: Post dose 1.\n14RSV A/B\n12.1 8.7 17.9\n1001,00010,000100,000\nPivotal Efficacy Study \"RENOIR\" \n≥ 60 YearsImmunocompromised and High Risk Study\n≥ 18 YearsAt Risk Immunobridging Study\n18–59 YearsRSV 50% Neutralizing GMTsBefore Vax 1M after Dose 1\n1. Severity definition: mild = no interference with daily activity; moderate = some interference with daily activity; severe = prevents daily activity.\n2. Severity definition: mild = >2 –5 cm, moderate = >5 –10 cm; severe = >10 cm.\n15\n0%20%40%60%80%100%\n18 to <60 ≥60 18 to <60 ≥60 18 to <60 ≥60% of Participation\n0%20%40%60%80%100%\n18 to <60 ≥60 18 to <60 ≥60 18 to <60 ≥60% of Participation\nMild Moderate SevereInjection Site Pain Redness Swelling\nInjection Site Pain Redness Swelling26% \n6.3% 3.7% 8.3% 2.8%16.8%\n46.8% \n2.1% 3.8% 3.2% 9.5%31.4% \n16\n0%20%40%60%80%100%\n18 to \n<60≥60 18 to \n<60≥60 18 to \n<60≥60 18 to \n<60≥60 18 to \n<60≥60 18 to \n<60≥60 18 to \n<60≥60 18 to \n<60≥60% of Participation\n0%20%40%60%80%100%\n18 to \n<60≥60 18 to \n<60≥60 18 to \n<60≥60 18 to \n<60≥60 18 to \n<60≥60 18 to \n<60≥60 18 to \n<60≥60 18 to \n<60≥60% of Participation\nMild Moderate Severe1.0% 0.9% Fatigue Fever Headache Vomiting Diarrhea Nausea Muscle Pain Joint Pain\n39.6% 44.9% 38.5% \n22.4% \n4.2% 0.9% 12.5% 8.4% 21.9% 17.8% 26% 20.6% 17.7% 21.5% \n0.0% 0.0% Fatigue Fever Headache Vomiting Diarrhea Nausea Muscle Pain Joint Pain\n37.2% 42.9% \n24.5% 25.7% \n2.1% 1.0% 6.4% 6.7% 11.7% 13.3% 19.1% 23.8% \n11.7% 17.1% \nAE: Adverse Event, AESI: Adverse Event of Special Interest (Guillain -Barré Syndrome, Acute polyneuropathy without an underlying etiology, Atrial Fibrillation, Preterm delivery, Hypertensive disorder of \npregnancy), SAE: Serious Adverse Event, NDCMC: Newly Diagnosed Chronic Medical Condition.\nFrom Vaccination Through 1 -Month after Dose 2 Follow -Up Visit \nAny Event 13 (13.5) 24 (22.4)\nSevere 2 (2.1) 4 (3.7)\nRelated 0 2 (1.9)\nFrom Vaccination Throughout the Study\nAE of Special Interest 0 2 (1.9)\nSAE 7 (7.3) 15 (14.0)\nAEs leading to withdrawal after Dose 1 2 (2.1) 0\nAE Leading to Death 0 0\nNDCMCs 2 (2.1) 7 (6.5)\n17\nAE: Adverse Event, AESI: Adverse Event of Special Interest (Guillain -Barré Syndrome, Acute polyneuropathy without an underlying etiology, Atrial Fibrillation, Preterm delivery, Hypertensive disorder of \npregnancy), SAE: Serious Adverse Event, NDCMC: Newly Diagnosed Chronic Medical Condition.\nFrom Vaccination Through 1 -Month after Dose 2 Follow -Up Visit \nAny Event 13 (13.5) 24 (22.4)\nSevere 2 (2.1) 4 (3.7)\nRelated 0 2 (1.9)\nFrom Vaccination Throughout the Study\nAE of Special Interest 0 2 (1.9)\nSAE 7 (7.3) 15 (14.0)\nAEs leading to withdrawal after Dose 1 2 (2.1) 0\nAE Leading to Death 0 0\nNDCMCs 2 (2.1) 7 (6.5)\n18\nFrom Vaccination Through 1 -Month after Dose 2 Follow -Up Visit \nAny Event 13 (13.5) 24 (22.4)\nSevere 2 (2.1) 4 (3.7)\nRelated 0 2 (1.9)\nFrom Vaccination Throughout the Study\nAE of Special Interest 0 2 (1.9)\nSAE 7 (7.3) 15 (14.0)\nAEs leading to withdrawal after Dose 1 2 (2.1) 0\nAE Leading to Death 0 0\nNDCMCs 2 (2.1) 7 (6.5)\nAE: Adverse Event, AESI: Adverse Event of Special Interest (Guillain -Barré Syndrome, Acute polyneuropathy without an underlying etiology, Atrial Fibrillation, Preterm delivery, Hypertensive disorder of \npregnancy), SAE: Serious Adverse Event, NDCMC: Newly Diagnosed Chronic Medical Condition.1 | Pain in the extremity\n 2 | Atrial Fibrillation\n19\nAE: Adverse Event, AESI: Adverse Event of Special Interest (Guillain -Barré Syndrome, Acute polyneuropathy without an underlying etiology, Atrial Fibrillation, Preterm delivery, Hypertensive disorder of \npregnancy), SAE: Serious Adverse Event, NDCMC: Newly Diagnosed Chronic Medical Condition.\nFrom Vaccination Through 1 -Month after Dose 2 Follow -Up Visit \nAny Event 13 (13.5) 24 (22.4)\nSevere 2 (2.1) 4 (3.7)\nRelated 0 2 (1.9)\nFrom Vaccination Throughout the Study\nAE of Special Interest 0 2 (1.9)\nSAE 7 (7.3) 15 (14.0)\nAEs leading to withdrawal after Dose 1 2 (2.1) 0\nAE Leading to Death 0 0\nNDCMCs 2 (2.1) 7 (6.5)1 | Atrial Fibrillation\n 2 | Atrial Fibrillation\n20\nAE: Adverse Event, AESI: Adverse Event of Special Interest (Guillain -Barré Syndrome, Acute polyneuropathy without an underlying etiology, Atrial Fibrillation, Preterm delivery, Hypertensive disorder of \npregnancy), SAE: Serious Adverse Event, NDCMC: Newly Diagnosed Chronic Medical Condition.\nFrom Vaccination Through 1 -Month after Dose 2 Follow -Up Visit \nAny Event 13 (13.5) 24 (22.4)\nSevere 2 (2.1) 4 (3.7)\nRelated 0 2 (1.9)\nFrom Vaccination Throughout the Study\nAE of Special Interest 0 2 (1.9)\nSAE 7 (7.3) 15 (14.0)\nAEs leading to withdrawal after Dose 1 2 (2.1) 0\nAE Leading to Death 0 0\nNDCMCs 2 (2.1) 7 (6.5)\n21\nRSVpreF was well -tolerated with no safety \nconcerns among immunocompromised adults \naged 18 years or older\n1 dose of RSVpreF elicited high GMT s and GMFRs \nin the immunocompromised study populations \nwith no additional increase after a second dose \n1 month apart\n22\nKPSC, Kaiser Permanente Southern California•Revaccination through 5 RSV \nseasons•Chronic \nmedical \nconditions\n•Non -\ninferiority \ndemonstrated •Immuno - \ncompromising \nand High Risk \nconditions \n•Efficacy \nthrough 2 \nseasons•Efficacy  \n(including \nImmunocomp\nromised and \nHigh Risk)•Non -\ninferiority \ndemonstrated•Non -\ninferiority \ndemonstrated\nOngoing Ongoing\nImmunocompromised, or renal, \nor hepatic impaired in EUGuillain -Barré Syndrome in US Atrial Fibrillation in US among \nVA patientsNear Real -time Guillain -Barré \nSyndrome in US\nAdults ≥ 60Adults \n18–59 Adults ≥ 18 Adults ≥ 65 Adults ≥ 65 Adults ≥ 60\n23\n2434\n3729\nAbrysvo Alone\nAbrysvo + 1\nAbrysvo +2 or more\n(n= 855, 200)\nMedAdvisor  Solutions. Abrysvo  coadministration with 2 vaccines in adults 60 years of \nage and older in Retail Pharmacies for October 2023. Unpublished data. October 2024\nMedAdvisor  Solutions network covers about 65% of the US population (around 218 \nmillion patients) through 33,500 retail or grocer pharmacies.  \nVaccine \nadministration IMBlood draw for \nimmunogenicityReactogenicity \ne-diarye\nCOVID  = Comirnaty \nRSVpreF: Abrysvo \nQIV : Fluzone HD Quad         \nPLB  = Placebo\nAssessing Safety, Tolerability and Non -inferiority Immunogenicity\n25Randomized, parallel \ngroup, observer -blinded \nstudy\n30 sites in the USA\n~750 participants \naged ≥65 years\n•No Prior RSV Vaccine \n•No Flu vaccine ≤120 days\n•At least 3 prior COVID -19 \nvaccines ≥150 days prior\nAbbreviations: AE, adverse event; AESIs, adverse event of special interest; NDCMC , \nnewly diagnosed chronic medical condition; SAE, serious adverse event.\nClinicaltrials.gov NCT05886777COVID + PLB\nRSV + PLB\nQIV + PLB\nRSV + COVID + PLB\nRSV + COVID + QIV\nGroups  (n~150 per Group)+ e\nSex n (%) n (%) n (%) n (%) n (%)\nFemale 80 (53.3) 80 (52.6) 79 (53.0) 94 (59.9) 83 (52.5)\nRace\nWhite 131 (87.3) 140 (92.1) 135 (90.6) 139 (88.5) 138 (87.3)\nBlack or African American 13 (8.7) 10 (6.6) 9 (6.0) 14 (8.9) 13 (8.2)\nAmerican Indian or Alaska Native 1 (0.7) 0 1 (0.7) 0 1 (0.6)\nAsian 2 (1.3) 1 (0.7) 3 (2.0) 3 (1.9) 5 (3.2)\nOther 3 (2) 1 (0.7) 1 (0.7) 1 (0.6) 1 (0.6)\nEthnicity\nHispanic/Latino 10 (6.7) 17 (11.2) 12 (8.1) 18 (11.5) 15 (9.5)\nAge at Vaccination (Years)\nMedian (min, max) 70 (65, 87) 71 (65, 85) 71 (65, 87) 70 (65, 87) 71 (65, 90)\nRace Other: Native Hawaiian or other Pacific Islander, Multiracial, or Not reported\n26\nAbbreviations: GMR  = geometric mean ratio; NTS0  = 50% neutralizing titer; SARS -CoV -2 = severe acute respiratory syndrome coronavirus 2.\nRSVPreF: NT: RSV -A 1.43 (1.131, 1.808)\nRSVPreF: NT: RSV -B 1.37 (1.060, 1.773)\nSARS -CoV -2 NT50 : Omicron BA.4 /BA.5 0.94 (0.673, 1.300)\nSARS -CoV -2 NT50 : Reference Strain 0.97 (0.740, 1.281)\n0.5 0.667 1.0 1.5 2.0\nGMT Ratio\n27\nAbbreviations: GMR = geometric mean ratio; HAI= hemagglutination inhibition assay; NTS0 = 50% neutralizing titer; SARS -CoV -2 = s evere acute respiratory syndrome coronavirus 2.0.5 1.0 2.0 3.0 4.0 5.0\nGMT Ratio\nRSVPreF: NT: RSV -A 1.42 (1.123, 1.801)\nRSVPreF: NT: RSV -B 1.27 (0.977, 1.651)\nSARS -CoV -2 NT: Omicron BA.4/BA.5 0.86 (0.610, 1.208)\nSARS -CoV -2 NT: Reference Strain 1.01 (0.764, 1.340)\nHAI: H1N1  A/Victoria 2.49 (1.914, 3.232)\nHAI: H3N2  A/Darwin 1.30 (1.049, 1.612)\nHAI: B/Austria 1.58 (1.155, 2.165)\nHAI: B/Phuket 3.49 (2.640, 4.604)\n28\nAbbreviations: GMR = geometric mean ratio; HAI= hemagglutination inhibition assay; NTS0 = 50% neutralizing titer; SARS -CoV -2 = s evere acute respiratory syndrome coronavirus 2.0.5 1.0 2.0 3.0 4.0 5.0\nGMT Ratio\nRSVPreF: NT: RSV -A 1.42 (1.123, 1.801)\nRSVPreF : NT: RSV -B 1.27 (0.977, 1.651)\nSARS -CoV -2 NT: Omicron BA.4/BA.5 0.86 (0.610, 1.208)\nSARS -CoV -2 NT: Reference Strain 1.01 (0.764, 1.340)\nHAI: H1N1  A/Victoria 2.49 (1.914, 3.232)\nHAI: H3N2  A/Darwin 1.30 (1.049, 1.612)\nHAI: B/Austria 1.58 (1.155, 2.165)\nHAI: B/Phuket 3.49 (2.640, 4.604)\n290.5\n0.667\n0%20%40%60%80%100%\nCOVID RSV QIV RSV + \nCOVIDRSV + \nCOVID \n+ QIVCOVID RSV QIV RSV + \nCOVIDRSV + \nCOVID \n+ QIVCOVID RSV QIV RSV + \nCOVIDRSV + \nCOVID \n+ QIV% of Participation\nMild Moderate SevereInjection Site Pain Redness Swelling\n62.7% \n10.5% 51.7% 56.7% 53.8% \n7.3% \n2.6% 4.0% 12.7% 8.9% 9.3% \n3.3% 6.0% 12.7% \n7% \n30\n0%20%40%60%80%100%\nCOVID RSV QIV RSV + \nCOVIDRSV + \nCOVID \n+ QIVCOVID RSV QIV RSV + \nCOVIDRSV + \nCOVID \n+ QIVCOVID RSV QIV RSV + \nCOVIDRSV + \nCOVID \n+ QIVCOVID RSV QIV RSV + \nCOVIDRSV + \nCOVID \n+ QIV% of Participation\nMild Moderate Severe\n5.3%10.5% 9.4%4.5%12.7%9.3%3.9% 2.0%10.2% 10.8% 8.7% 5.9% 4%10.2% 9.5% 10.7 9.9% 10.7%14.6% 14.0%0%20%40%60%80%100%\nCOVID RSV QIV RSV + \nCOVIDRSV + \nCOVID \n+ QIVCOVID RSV QIV RSV + \nCOVIDRSV + \nCOVID \n+ QIVCOVID RSV QIV RSV + \nCOVIDRSV + \nCOVID \n+ QIVCOVID RSV QIV RSV + \nCOVIDRSV + \nCOVID \n+ QIV% of ParticipationFever Vomiting Fatigue Headache\n35.3%\n24.3%28.9%38.9%46.8%\n22.7%19.1%12.8%24.2%19.0%\n1.3% 2.6% 0.7% 0.6% 1.3% 1.3% 0.0%1.9% 4.4%1.3%\nMuscle Pain Diarrhea Chills Joint Pain\n31\nFrom Vaccination Through 1 -Month Follow -Up Visit \nAny Event 12 (8) 11 (7.2) 12 (8.1) 14 (8.9) 14 (8.9)\nRelated 1 (0.7) 1 (0.7) 2 (1.3) 4 (2.5) 4 (2.5)\nImmediate 0 0 0 0 1 (0.6)\nSevere 1 (0.7) 0 0 0 1 (0.6)\nFrom Vaccination Throughout the Study\nSAE 4 (2.7) 2 (1.3) 2 (1.3) 1 (0.6) 3 (1.9)\nAE Leading to Death 0 0 0 0 0\nAE of Special Interest 9 (6) 2 (1.3) 3 (2) 5 (3.2) 4 (2.5)\nAE: Adverse Event, AESI: Adverse Event of Special Interest (COVID -19, positive SARS -CoV -2 test, Guillain -Barré Syndrome, Acute p olyneuropathy without an underlying etiology, Atrial fibrillation, \nPreterm delivery, Hypertensive disorder of pregnancy), SAE: Serious Adverse Event, NDCMC: Newly Diagnosed Chronic Medical Con dition.\n32\nFrom Vaccination Through 1 -Month Follow -Up Visit \nAny Event 12 (8) 11 (7.2) 12 (8.1) 14 (8.9) 14 (8.9)\nRelated 1 (0.7) 1 (0.7) 2 (1.3) 4 (2.5) 4 (2.5)\nImmediate 0 0 0 0 1 (0.6)\nSevere 1 (0.7) 0 0 0 1 (0.6)\nFrom Vaccination Throughout the Study\nSAE 4 (2.7) 2 (1.3) 2 (1.3) 1 (0.6) 3 (1.9)\nAE Leading to Death 0 0 0 0 0\nAE of Special Interest 9 (6) 2 (1.3) 3 (2) 5 (3.2) 4 (2.5)\nAE: Adverse Event, AESI: Adverse Event of Special Interest (COVID -19, positive SARS -CoV -2 test, Guillain -Barré Syndrome, Acute p olyneuropathy without an underlying etiology, Atrial fibrillation, \nPreterm delivery, Hypertensive disorder of pregnancy), SAE: Serious Adverse Event, NDCMC: Newly Diagnosed Chronic Medical Con dition.\n33\nFrom Vaccination Through 1 -Month Follow -Up Visit \nAny Event 12 (8) 11 (7.2) 12 (8.1) 14 (8.9) 14 (8.9)\nRelated 1 (0.7) 1 (0.7) 2 (1.3) 4 (2.5) 4 (2.5)\nImmediate 0 0 0 0 1 (0.6)\nSevere 1 (0.7) 0 0 0 1 (0.6)\nFrom Vaccination Throughout the Study\nSAE 4 (2.7) 2 (1.3) 2 (1.3) 1 (0.6) 3 (1.9)\nAE Leading to Death 0 0 0 0 0\nAE of Special Interest 9 (6) 2 (1.3) 3 (2) 5 (3.2) 4 (2.5)\nAE: Adverse Event, AESI: Adverse Event of Special Interest (COVID -19, positive SARS -CoV -2 test, Guillain -Barré Syndrome, Acute p olyneuropathy without an underlying etiology, Atrial fibrillation, \nPreterm delivery, Hypertensive disorder of pregnancy), SAE: Serious Adverse Event, NDCMC: Newly Diagnosed Chronic Medical Con dition.\n34\nFrom Vaccination Through 1 -Month Follow -Up Visit \nAny Event 12 (8) 11 (7.2) 12 (8.1) 14 (8.9) 14 (8.9)\nRelated 1 (0.7) 1 (0.7) 2 (1.3) 4 (2.5) 4 (2.5)\nImmediate 0 0 0 0 1 (0.6)\nSevere 1 (0.7) 0 0 0 1 (0.6)\nFrom Vaccination Throughout the Study\nSAE 4 (2.7) 2 (1.3) 2 (1.3) 1 (0.6) 3 (1.9)\nAE Leading to Death 0 0 0 0 0\nAE of Special Interest 9 (6) 2 (1.3) 3 (2) 5 (3.2) 4 (2.5)\nAE: Adverse Event, AESI: Adverse Event of Special Interest (COVID -19, positive SARS -CoV -2 test, Guillain -Barré Syndrome, Acute p olyneuropathy without an underlying etiology, Atrial fibrillation, \nPreterm delivery, Hypertensive disorder of pregnancy), SAE: Serious Adverse Event, NDCMC: Newly Diagnosed Chronic Medical Con dition.\n35\nAE: Adverse Event, AESI : Adverse Event of Special Interest (COVID -19, positive SARS -CoV -2 test, Guillain -Barré Syndrome, Acute polyneuropathy without a n underlying etiology, Atrial fibrillation, \nPreterm delivery, Hypertensive disorder of pregnancy), SAE: Serious Adverse Event, NDCMC : Newly Diagnosed Chronic Medical Condition.\nFrom Vaccination Through 1 -Month Follow -Up Visit \nAny Event 12 (8) 11 (7.2) 12 (8.1) 14 (8.9) 14 (8.9)\nRelated 1 (0.7) 1 (0.7) 2 (1.3) 4 (2.5) 4 (2.5)\nImmediate 0 0 0 0 1 (0.6)\nSevere 1 (0.7) 0 0 0 1 (0.6)\nFrom Vaccination Throughout the Study\nSAE 4 (2.7) 2 (1.3) 2 (1.3) 1 (0.6) 3 (1.9)\nAE Leading to Death 0 0 0 0 0\nAE of Special Interest 9 (6) 2 (1.3) 3 (2) 5 (3.2) 4 (2.5)\n36\nSafety and immunogenicity was demonstrated for a single dose of RSVpreF \nin IC and HR adultsCo-administration is common; safety and immunogenicity data supports ACIP \nco-administration guidelines regarding RSVpreF with COVID and/or \nwith Influenza Vaccines.\nOngoing Clinical T rials and Post -Licensure Studies continue to provide meaningful \ndata to assess the safety, effectiveness, and benefit/risk of the product. There have \nbeen no new safety concerns identified in the post -licensure period to date.\n37", "summary": "ACIP Presentation October 24, 2024 Iona Munjal, MD, FAAP Clinical Research and  Development, Pfizer Vaccines Bivalent Stabilized Prefusion F RSV A and RSV B strains Adult Active immunization for the prevention of LRTD  caused by RSV in individuals 60 years of age and  older.Maternal Active immunization of pregnant individuals at 32  through 36 weeks gestational age for the  prevention of lower respiratory tract disease  (LRTD) and severe LRTD caused by respiratory  syncytial virus (RSV) in…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-23-24-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/03-RSV-Adult-Munjal-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 38}
{"title": "04 RSV Adult Gerber 508", "content": "CO-1\nMeeting of the Advisory Committee on \nImmunization Practices (ACIP)\nCenters for Disease Control and Prevention\nOctober 24, 2024\nSusan Gerber, MD\nMedical Director \nGSK\nPresentation by GSK at ACIP October 24, 2024\n\nCO-2\n~ 9 million AREXVY doses administered in US to dateAREXVY Indications \nAREXVY is indicated for active immunization for prevention of lower respiratory \ntract disease (LRTD) caused by RSV in\nIndividuals ≥ 60 YOA\nIndividuals 50-59 YOA at increased risk for LRTD caused by RSV\nYOA, years of age\nFDA, 2024. AREXVY Prescribing Information (PI); https://www.fda.gov/media/167805/download (URL accessed Aug 2024)\n\nCO-3\nRSV- OA=ADJ -023: Immune response and safety among adult \nlung and kidney transplant recipients ≥ 18 years of age \nPreliminary results\nA Phase 2b, randomized, controlled, open- label study to evaluate the immune response \nand safety of the RSVPreF3 + AS01E vaccine in adults (≥18 years of age) when \nadministered to lung and kidney transplant recipients comparing a 1 versus a 2- dose \nschedule and compared to adults (≥50 years of age) receiving 1 dose\nNCT 05921903\n\nCO-4\nRSV- OA=ADJ -023: Phase 2b Study Design\nDescriptive immunogenicity and safety study in lung and kidney transplant recipients ≥ 18 YOA versus adults ≥ 50 YOA\n1-dose; n=125Study initiation:\n July 2023Visit 2*\n 7–14 days \npost-Dose 1Visit 3\n1 month***\npost-Dose 1\nCohort 1 \nAdults with \nSOT ≥ 18 YOA\nN=261\n1-dose; n=131\nLung SOT, n=39 \nKidney SOT, n=92\n2-dose; n=130\nLung SOT, n=36\nKidney SOT, n=94Visit 4\n1 month\npost-Dose 2****Visit 6\n12 months\npost-last doseVisit 5\n6 months\npost-last doseVisit 1\nDay 1\nSafety \nanalysesSolicited AEs Within 7 days of a vaccine dose\nUnsolicited AEs Within 30 days of a vaccine dose\nSAEs, pIMDs , and AESIs related to transplantation Up to end of studyCurrent analysis\nAdults \n≥ 50 YOA\nN=125\n*Only in subset of study population, ~30% of participants; **Blood sample for CMI analysis collected at each visit only in su bset of study population (~30% of participants); \n***Allowed interval range: 30 -60 days; ****For Adults with SOT 1 -dose group and Adults ≥ 50 YOA, Visit 4 refers to 1 -month post- Visit 3; AE, adverse event; AESI, adverse event of special interest; \nCMI, cell- mediated immunity; HI, humoral immunity; pIMD , potential immune -mediated disorder; SAE, serious adverse event; SOT, solid organ transplant; YOA, years of ageRSVPreF3 + AS01E \nBlood sample; HI, CMI**Cohort 2RSV-OA=ADJ -023 \nR\n1:1\n\nCO-5\nKey Inclusion and Exclusion Criteria\nAdults with SOT (kidney & lung) ≥ 18 YOA\nInclusion criteria: \nABO compatible allogeneic kidney or lung transplant (allograft) \n> 12 months prior to first study intervention\nReceiving maintenance immunosuppressive therapy for prevention of allograft rejection\nExclusion criteria: \nAllograft rejection in 3 months prior to first dose\nCurrent diagnosis of malignancy\nUse of anti -CD20 or other B -cell mAb agents for prevention of allograft \nrejection within 9 months of first doseInclusion criteria:  Stable lung function \nExclusion criteria:\n•Acute pulmonary infection with 2 weeks of study intervention visit\n•Diagnosis of chronic lung allograft dysfunction LungInclusion criteria:  Stable renal function \nExclusion criteria: \n•Previous allograft loss secondary to recurrent primary kidney disease\n•Significant proteinuria/albuminuriaKidney\nInclusion criteria:\nMedically stable in investigator’s opinion\nParticipants with chronic stable conditions with or without specific treatment (e.g., diabetes mellitus, hypertension, cardiac disease)\nExclusion criteria:\nImmunosuppressive or immunodeficient conditions\nUnstable chronic illnessAdults ≥ 50 YOA\nABO, ABO blood group system; CD, cluster of differentiation; mAb , monoclonal antibody; SOT, solid organ transplant; YOA, years of age\nClinicalTrials.gov. NCT05921803. https://www.clinicaltrials.gov/study/NCT05921903  (accessed September 2024)RSV-OA=ADJ -023 \n\nCO-6\nDemographic Characteristics Generally Balanced Between Groups\n(Exposed Set)\nCharacteristicAdults with SOT ≥ 18 YOA Adults ≥ 50 YOA\nTotal\n(N=386)1-dose group\n (N=131)2-dose group \n(N=130)1-dose group\n (N=125)\nAge (years) at vaccination, mean (SD) 61.9 (9.3) 61.4 (8.4) 63.8 (8.2) 62.4 (8.7)\nAge category, n (%)\n18–49 YOA 9 (6.9) 8 (6.2) 0 (0.0) 17 (4.4)\n50–59 YOA 37 (28.2) 41 (31.5) 44 (35.2) 122 (31.6)\n≥ 60 YOA 85 (64.9) 81 (62.3) 81 (64.8) 247 (64.0)\nSex, n (%)\nFemale 54 (41.2) 50 (38.5) 66 (52.8) 170 (44.0)\nEthnicity, n (%)\nHispanic or Latino 12 (9.2) 5 (3.8) 22 (17.6) 39 (10.1)\nRace, n (%)\nAmerican Indian or Alaska Native 0 (0.0) 1 (0.8) 0 (0.0) 1 (0.3)\nAsian 26 (19.8) 33 (25.4) 10 (8.0) 69 (17.9)\nBlack or African American 11 (8.4) 8 (6.2) 4 (3.2) 23 (6.0)\nWhite 89 (67.9) 79 (60.8) 95 (76.0) 263 (68.1)\nNot reported or unknown 4 (3.1) 9 (6.9) 15 (12.0) 28 (7.3)\nMultiple 1 (0.8) 0 (0.0) 1 (0.8) 2 (0.5)\nSOT type, n (%)\nLung transplant 39 (29.8) 36 (27.7) - -\nKidney transplant 92 (70.2) 94 (72.3) - -\nInterval between last transplantation and Visit 1 \n(months), median (min, max) 67 (12, 386) 60 (14, 450) - -RSV-OA=ADJ -023 \nAdults with SOT 1 -dose group: adults with kidney and lung transplant ≥18 YOA receiving 1 dose of RSVPreF3 + AS01E at Visit 1 (Day 1); Adults with SOT 2 -dose group: adults with kidney and lung \ntransplant ≥18 YOA receiving 2 doses of RSVPreF3 + AS01E at Visit 1 (Day 1) and Visit 3 (30– 60 days post -Dose 1); Adults ≥50 YOA group: adults ≥50 YOA receiving 1 dose of RSVPreF3 + AS 01E at \nVisit 1 (Day 1); SD, standard deviation; SOT, solid organ transplant; YOA, years of age\n\nCO-7\nWorldwide Study Including 8 Countries \nCanada (n=47)\nAustralia (n=26)\nJapan (n=61)\nItaly (n=28)\nGermany (n=14)\nUnited States (n=104)\nAdults with SOT \n≥ 18 YOAAdults \n≥ 50 YOA\n1-dose \ngroup2-dose \ngroup 1-dose \ngroup\nn (%) 39 (29.8) 33 (25.4) 32 (25.6)\nSOT type, n (%)\nLung 10 (25.6) 8 (22.2) -\nKidney 29 (31.5) 25 (26.6) -\nSpain (n=82)RSV-OA=ADJ -023 \nSouth Korea \n(n=24)\n\nCO-8\nImmunogenicity\nPreliminary results\n\nCO-9\nCo-primary Endpoints: RSV -A and RSV -B NAbs  Higher at \n1 Month Post -Dose 2 vs Post- Dose 1 in Adults with SOT ≥ 18 YOA \nReceiving 2 Doses of RSVPreF3 + AS01E*\nNRSV-A NAb titers expressed as\nMGI ratio MGI ratio (95% CI)\n111 1.34 (1.20, 1.48)MGI =1 month  post−Dose  2 (Visit  4) \n1 month  post−Dose  1 (Visit  3)\n RSV-A\nMGI =1 month  post−Dose  2 (Visit  4)\n1 month  post−Dose  1 (Visit  3)\n RSV-B0.5 1.0 1.5 2.0\nNRSV-B NAb titers expressed as\nMGI ratio MGI ratio (95% CI)\n111 1.26 (1.14, 1.40)\n0.5 1.0 1.5 2.0\n*Adults with SOT ≥ 18 YOA receiving 2 doses of RSVPreF3 + AS01E at Visit 1 (Day 1) and Visit 3 (30– 60 days post -Dose 1)\nCI, confidence interval; MGI, mean geometric increase; NAb, neutralizing antibody; SOT, solid organ transplant; YOA, years of ageRSV-OA=ADJ -023 \n\nCO-10\nRSVPreF3 + AS01E Elicits Robust Humoral Immune \nResponses in Kidney and Lung Transplant Recipients\nSOT 1 -dose 114 114 114\nSOT 2 -dose 110 110 110\n≥ 50 YOA 105 105 105GMT, \nED60 \n(95% CI)\n5005000\nGMT, \nED60\n (95% CI)\nVisit 3\n1 month \npost-Dose 1Visit 1 Visit 4\n1 month \npost-Dose 2**5005000\n0 0.5 1 1.5 2\nSOT 1 -dose 114 114 114\nSOT 2 -dose 110 110 110\n≥ 50 YOA 105 105 105Visit 4\n1 month \npost-Dose 2**Visit 1 Visit 3\n1 month \npost-Dose 1\n*In participants with results available at all timepoints; **For Adults with SOT 1 -dose group and Adults ≥50 YOA, Visit 4 refers to 1 month post- Visit 3\nAdults with SOT 1 -dose group: adults with kidney and lung transplant ≥18 YOA receiving 1 dose of RSVPreF3 + AS01E at Visit 1 (Day 1); Adults with SOT 2 -dose group: adults with kidney and lung \ntransplant ≥18 YOA receiving 2 doses of RSVPreF3 + AS01E at Visit 1 (Day 1) and Visit 3 (30– 60 days post -Dose 1); Adults ≥50 YOA group: adults ≥50 YOA receiving 1 dose of RSVPreF3 + AS 01E at \nVisit 1 (Day 1); CI, confidence interval; ED60, estimated dilution 60; GMT, geometric mean titer; NAb, neutralizing antibody; SOT, solid organ transplant; YOA, years of ageRSV-OA=ADJ -023 \nRSV-A NAbs * RSV-B NAbs *\nAdults with SOT ≥ 18 YOA \n1-doseAdults with SOT ≥ 18 YOA 2-doseAdults ≥ 50 YOAn n\n\nCO-11\n5005000\n5005000\n5005000\n5005000\n5005000\n5005000RSVPreF3 + AS01E Induced Similar RSV -A and RSV -B Neutralizing \nAntibody Responses in Kidney and Lung Transplant Recipients\nGMT, \nED60 \n(95% CI)\nVisit 3\n1 month \npost-Dose 1Visit 1 Visit 4\n1 month \npost-Dose 2*\nKidney 1 dose 89 88 83\nKidney 2 dose 90 84 81\nLung 1 dose 34 35 33\nLung 2 dose 33 30 30Visit 3\n1 month \npost-Dose 1Visit 1 Visit 4\n1 month \npost-Dose 2*GMT, \nED60 \n(95% CI)\n*For Adults with SOT 1 -dose group, Visit 4 refers to 1 month post- Visit 3; Adults with SOT 1 -dose group: adults with kidney and lung transplant ≥18 YOA receiving 1 dose of RSVPreF3 + AS01E at Visit \n1 (Day 1); Adults with SOT 2 -dose group: adults with kidney and lung transplant ≥18 YOA receiving 2 doses of RSVPreF3 + AS01E at Visit 1 (Day 1) and Visit 3 \n(30–60 days post -Dose 1);CI, confidence interval; ED60, estimated dilution 60; GMT, geometric mean titer; SOT, solid organ transplant; YOA, years of ageRSV-OA=ADJ -023 \nRSV-A NAbs RSV-B NAbs\n1 dose 2 doseKidney transplant\n1 dose 2 doseLung transplantKidney 1 dose 89 88 83\nKidney 2 dose 90 84 81\nLung 1 dose 34 35 33\nLung 2 dose 33 30 30n n\n\nCO-12\nSOT \n1-doseMC 94 94 88\nNo MC 29 29 28\nSOT \n2-doseMC 93 89 87\nNo MC 30 25 24\n≥ 50 YOA 125 118 1105005000\n5005000\n5005000\nSOT \n1-doseMC 94 94 88\nNo MC 29 29 28\nSOT \n2-doseMC 93 89 87\nNo MC 30 25 24\n≥ 50 YOA 125 118 1105005000\n5005000\n5005000Differences in RSV -A and RSV -B Neutralizing Antibody Responses \nInduced by RSVPreF3 + AS01E by Presence or Absence of Mycophenolate \nGMT, \nED60 \n(95% CI)GMT, ED60 \n(95% CI)\nVisit 1 Visit 4\n1 month \npost-Dose 2*Visit 3\n1 month \npost-Dose 1Visit 1 Visit 4\n1 month \npost-Dose 2 *Visit 3\n1 month \npost-Dose 1\n*For Adults with SOT 1 -dose group and Adults ≥50 YOA, Visit 4 refers to 1 month post- Visit 3; Adults with SOT 1 -dose group: adults with kidney and lung transplant ≥18 YOA receiving 1 dose of \nRSVPreF3 + AS01E at Visit 1 (Day 1); Adults with SOT 2 -dose group: adults with kidney and lung transplant ≥18 YOA receiving 2 doses of RSVPreF3 + AS01E at Visit 1 (Day 1) and Visit 3 (30– 60 days \npost- Dose 1); CI, confidence interval; ED60, estimated dilution 60; GMT, geometric mean titer; MC, mycophenolate; SOT, solid organ transplant; YOA, years of ageRSV-OA=ADJ -023 \nRSV-A NAbs RSV-B NAbs\nMC No MCAdults with SOT ≥ 18 YOA\n1-dose\nMC No MCAdults with SOT ≥ 18 YOA\n2-dose Adults ≥ 50 YOAn n\n\nCO-13\nRSVPreF3 + AS01E Induces Robust CD4+ T -cell Responses in \nKidney and Lung Transplant Recipients \nMedianQ3\nQ1\nMinimumMaximumKey\nn 23 24 22 23 28 27 28 26 31 28 24 28\nIncreased CD4+ T -cell \nresponses were \nconsistent across  \nimmunocompromised \ngroups (1- dose, 2- dose) \nand adults ≥ 50 YOA\n1.010.0100.01000.010000.0\nFrequency of \nRSVPreF3 -specific \nCD4+ T -cells* \n(per million of \nCD4+ T -cells)\nV1 V2 V3 V4\nAdults with SOT ≥ 18 YOA\n1-dose groupAdults with SOT ≥ 18 YOA\n2-dose groupV1 V3 V4 V1 V2 V4 V2 V3\nAdults ≥ 50 YOA\n*Expressing ≥ 2 activation markers including ≥1 cytokine among CD40L, 4- 1BB, IL -2, TNF -α, IFN-γ, IL-13, and IL -17\nAdults with SOT 1 -dose group: adults with kidney and lung transplant ≥ 18 YOA receiving 1 dose of RSVPreF3 + AS01E at Visit 1 (Day 1); adults with SOT 2 -dose group: adults with kidney and lung \ntransplant ≥ 18 YOA receiving 2 doses of RSVPreF3 + AS01E at Visit 1 (Day 1) and Visit 3 (30– 60 days post -Dose 1); Adults ≥50 YOA group: adults ≥ 50 YOA receiving 1 dose of RSVPreF3 + A S01E at \nVisit 1 (Day 1); CD, cluster of differentiation; IFN, Interferon; IL, interleukin; SOT, solid organ transplant; TNF, tumor necrosis factor; V,  Visit; YOA, years of ageRSV-OA=ADJ -023 \n\nCO-14\nSafety\nPreliminary results\n\nCO-15\nSolicited AEs Broadly Similar Between SOT Groups and ≥ 50 YOA \nGroup (Within 7 Days Post- Vaccination)\nGrade 3 AEs were defined as administration -site erythema or swelling with a diameter >100 mm, fever with a temperature >39.0° C/102.2° F, and administration -site pain, headache, fatigue, myalgia, and \narthralgia that prevented normal activity. Adults with SOT 1 -dose group: adults with kidney and lung transplant ≥18 YOA receiving 1 dose of RSVPreF3 + AS01E at Visit 1 (Day 1); Adults with SOT 2 -\ndose group: adults with kidney and lung transplant ≥18 YOA receiving 2 doses of RSVPreF3 + AS01E at Visit 1 (Day 1) and Visit 3 (30– 60 days post -Dose 1); Adults ≥50 YOA group: adults ≥50 YOA \nreceiving 1 dose of RSVPreF3 + AS01E at Visit 1 (Day 1); AE, adverse event; CI, confidence interval; SOT, solid organ transplant; YOA, years of age0102030405060708090100\nLocal SystemicErythema Arthralgia Fatigue Fever ≥38° C Headache Myalgia Swelling Pain8.5\n(5.4, 12.6)8.5\n(4.1, 15.0) 8.8\n(4.5, 15.2)72.2\n(66.3, 77.6) 68.6\n(59.5, 76.9)76.0 \n(67.5, 83.2)\n7.3\n(4.5, 11.2)5.1\n(1.9, 10.7)13.1\n(9.3, 17.9)16.1\n(10.0, 24.0)33.2\n(27.5, 39.3)39.8\n(30.9, 49.3)\n1.2\n(0.2, 3.3)1.7 \n(0.2, 6.0)24.7\n(19.6, 30.4)25.4\n(17.9, 34.3)29.0\n(23.5, 34.9)32.2\n(23.9, 41.4)\n2.4 \n(0.5, 6.9)12.0\n(6.9, 19.0)38.4\n(29.8, 47.5)\n0.8\n(0.0, 4.4)35.2\n(26.9, 44.2)39.2\n(30.6, 48.3)Post-Dose 1 \n(Pooled SOT 1-dose  and 2-dose  groups; N=259)\nPost-Dose 2 (SOT 2-dose  group; N=118)\nAdults ≥ 50 YOA (N=125)\nIncidence  of solicited Grade 3 AEs were low across groups (≤ 3% for any AE in any group)Participants \n% (95% CI)RSV-OA=ADJ -023 \n\nCO-16\n020406080100Related Unsolicited AEs Similar Between Groups\n(Within 30 Days Post -Vaccination) \nMost events in SOT groups \nreflect background \nmorbidity (e.g. range of \ninfections, gastrointestinal and general AEs) \nNo pattern or clustering of events types to suggest a \nsafety concern\nAdults with SOT 1 -dose group: adults with kidney and lung transplant ≥18 YOA receiving 1 dose of RSVPreF3 + AS01E at Visit 1 (Day 1); Adults with SOT 2 -dose group: adults with kidney and lung \ntransplant ≥18 YOA receiving 2 doses of RSVPreF3 + AS01E at Visit 1 (Day 1) and Visit 3 (30– 60 days post -Dose 1); Adults ≥50 YOA group: adults ≥50 YOA receiving 1 dose of RSVPreF3 + AS 01E at \nVisit 1 (Day 1); AE, adverse event; CI, confidence interval; SOT, solid organ transplant; YOA, years of ageParticipants \n% (95% CI)\nUnsolicited AEs Related unsolicited AEsRSV-OA=ADJ -023 \n6.1\n(3.5, 9.8)4.0 \n(1.3, 9.1)6.6\n(2.9, 12.6)20.7\n(15.9, 26.1)20.8 \n(14.1, 29.0)30.6\n(22.5, 39.6)Post-Dose 1\n(Pooled SOT 1-dose  and 2-dose  groups; N=261)\nPost-Dose 2\n(SOT 2-dose  group; N=121)\nAdults ≥ 50 YOA (N=125)\nGrade 3\n\nCO-17\nSAEs Similar Between Dose 1 and Dose 2 SOT Groups\n(Up to Safety Data Lock Point)\nAdults with SOT 1 -dose group: adults with kidney and lung transplant ≥18 YOA receiving 1 dose of RSVPreF3 + AS01E at Visit 1 (Day 1); Adults with SOT 2 -dose group: adults with kidney and lung \ntransplant ≥ 18 YOA receiving 2 doses of RSVPreF3 + AS01E at Visit 1 (Day 1) and Visit 3 (30– 60 days post -Dose 1); Adults ≥50 YOA group: adults ≥50 YOA receiving 1 dose of RSVPreF3 + AS 01E at \nVisit 1 (Day 1); CI, confidence interval; GBS, Guillain -Barré syndrome; pIMD , potential immune -mediated disease; SAE, serious adverse event; SOT, solid organ transplant; YOA, years of ageParticipants \n% (95% CI)\n020406080100\n3.8\n(1.3, 8.7)2.4 \n(0.5, 6.9)10.7\n(5.8, 17.7)9.2\n(4.8, 15.5)\nPost -Dose 1 \nSOT 1-dose  group Post -Dose 1 \nSOT 2-dose  group Post -Dose 2 \nSOT 2-dose  group Post -Dose 1 \nAdults ≥50 YOA\nN 131 130 121 125\nMedian \nfollow -up170 days 30-60 days 136 days 171 daysNo specific pattern or clustering of SAEs \nNo cases of GBS or atrial fibrillationRSV-OA=ADJ -023 \n\nCO-18\nAReSVi -006 Pivotal Efficacy Study: \nPreliminary Updates from Season 3\nPhase 3, Randomized, Placebo- Controlled, Multi -Country Study to Demonstrate Efficacy & \nSafety of Single & Annual Revaccination Doses in Adults 60 Years & Older \nNCT04886596\n\nCO-19\nRSV annual (N=4,968)\nRSV 1 dose (N=4,988)\nPlacebo (N=10,031)RSV Season 1AReSVi -006 Phase 3 Trial Design1-4\nRandomization (1:1)Re-randomization (1:1)RSV Season 2 RSV Season 3\nRSVPreF3 + AS01E\n(N=12,468)\nPlacebo \n(N=12,498)D1RSVPreF3 + AS01E\nPlacebo\nOlder adults \n≥ 60 YOANH: 1st Oct 2021 to 30 Apr 2022\nSH: 1st Mar 2022 to 30 Sep 2022NH: 1st Oct 2022 to 31 Mar 2023\nSH: 1st Mar 2023 to 30 Sep 2023\nPrimary endpoint: To demonstrate efficacy of RSVPreF3 + AS01E in prevention of RSV LRTD** in adults ≥ 60 YOA during first season2\nConfirmatory secondary endpoints: To demonstrate efficacy of RSVPreF3 + AS01E in the prevention of RSV LRTD ** in adults ≥ 60 YOA over three seasons, \nfollowing a single dose and annual revaccination of RSVPreF3 + AS01E, and for each RSV subgroup (A and B) separately2\nAll RSV -LRTD** cases adjudicated by independent external adjudication committeeNH: 1st Oct 2023 to 30 Apr 2024\nSH: 1st Mar 2024 to 30 Apr2024\nRSV annual 1+1(N=3,582)\n4,*\nFigure adapted from Ison  MG et al. Clin Infect Dis 2024. under the terms of the CC BY 4.0 Attribution License (https://creativecommons.org/licenses/by/4.0/ ); *Some participants in NH who came at \ntheir Pre -season 3 visit before the approval of protocol amendment 5 received Dose 3; **LRTD defined as ≥2 lower respiratory symptoms/signs for ≥24 hours including ≥1 lower respiratory sign OR \n≥3 lower respiratory symptoms for ≥24 hours. All cases of RSV were RT -PCR confirmed; D, day; LRTD, lower respiratory tract disea se; N, number of participants in the modified exposed set (S1), \ndose 2- modified exposed set (S2), participants in the dose 2 -modified exposed set who did not receive dose 3 (RSV annual group); \nNH, Northern Hemisphere; RT -PCR, reverse transcription -polymerase chain reaction; S, season; SH, Southern Hemisphere; YOA, years of age; \n1. ClinicalTrials.gov, 2024. NCT04886596.; 2. Papi  A et al. N Engl J Med 2023;388:595– 608; 3. Ison MG et al. Clin Infect Dis 2024;78:1732– 1744; 4. Unpublished dataEnd of \nStudy\nAnalysis\nStudy start \nNH: 25 May 20212AReSVi- 006\nRR\n\nCO-20\n~25,000 Participants Randomized in 17 Countries\nNorthern Hemisphere \n(N=23,018 \nincl. ~9,000 in NA)\nSouthern Hemisphere \n(N=1,948)\nAustria \nBelgiumEstoniaFinlandGermanyItalyPolandRussiaSpainUK\nJapanSouth Korea\nCanadaUnited StatesMexico\nAustraliaNew Zealand\nSouth Africa\nRSVPreF3 Vaccine for Respiratory Syncytial Virus (RSV) in Older Adults. Presented at VRBPAC Meeting, March 1, 2023; FDA.gov (URL  accessed August 2024); \nNA, North America; UK, United Kingdom; VRBPAC, Vaccines and Related Biological Products Advisory CommitteeAReSVi- 006\n\nCO-21\nAReSVi -006 Case Definitions1,2\nSigns and symptoms in addition to ≥ 1 RSV -positive swab detected by qRT-PCR\nARI\n≥ 2 respiratory  symptoms or signsOR\n \n≥ 1 respiratory and 1 systemic symptom or sign for at least 24 hours Respiratory symptoms or signs\nFever/feverishness\nFatigue\nBody aches\nHeadache\nDecreased appetiteUpper respiratory symptoms \nor signsLower respiratory \nsymptomsLower respiratory signsSystemic symptoms or signs\nSputum\nCough\nDyspneaWheezing\nCrackles/rhonchi\nTachypnea\nHypoxemia\nO2 supplementNasal congestion\nSore throat\nLRTD*≥ 2 lower respiratory symptoms or signs (≥ 1 sign) OR\n  \n≥ 3 lower respiratory symptoms for at least 24 hours Sputum\nCough\nDyspneaLower respiratory \nsymptomsLower respiratory signs\nWheezing\nCrackles/rhonchi\nTachypnea\nHypoxemia\nO\n2 supplement\nSevere LRTD*≥ 2 lower respiratory signsOR\nepisode preventing normal,everyday activitiesLower respiratory signs\nWheezing\nCrackles/rhonchi\nTachypnea\nHypoxemia\nO\n2 supplement\n*USPI case definitions ; ARI, acute respiratory infection; LRTD, lower respiratory tract disease; qRT-PCR, quantitative reverse transcription -polymerase chain reaction; \n1. GSK’s RSVPreF3 OA Vaccine (AREXVY). Presented at ACIP, 21 June 2023 https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2023- 06-21-23/03- RSV- Adults -Friedland -508.pdf  (URL \naccessed August 2024); 2. Papi  A et al. N Engl J Med 2023;388:595– 608AReSVi- 006\n\nCO-22\nSingle Dose of RSVPreF3 + AS01E Demonstrates Clinically \nMeaningful Vaccine Efficacy Against RSV -LRTD* Over 3 RSV \nSeasons1-4\n*VE is maintained up to end of Season 3 NH. Confirmatory secondary endpoint is demonstrated with LL >20%; **96.95% CI; ***97.5% CI; ****95% CI; *****VE was estimated using a Poisson model \nadjusted for age, region, and season (“with season as a covariate”) or for age and region (“without season as a covariate”; p ost-hoc analyses). For Season only VE, season could not be considered a \ncovariate, so data are presented in the “without season as a covariate” column; CI, confidence interval; LRTD, lower respirat ory tract disease; m, month; n/a, not applicable; NH, Northern Hemisphere; \nS, Season; SH, Southern Hemisphere; VE, vaccine efficacy .\n1. Papi  A et al. N Engl J Med 2023;388:595– 608; 2. Ison MG et al. Clin Infect Dis 2024;78:1732– 1744; 3. Gerber S. AREXVY (Adjuvanted RS VPreF3) 2 -Year Update. Presented at ACIP 26 June 2024. \nhttps://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2024- 06-26-28/03- RSV- Adult- Gerber -508.pdf (accessed August 2024); 4.  Unpublished dataSeason \n(median follow -up time)RSVPreF3 + \nAS01E Placebo% VE (CI)*****\nW/ season \ncovariateW/o season \ncovariate Number of events (n/N) \nSeason 1** (end of NH S1; 6.7m)\n1 7 / 12,466 40 / 12,494 n/a 82.6 (57.9, 94.1)\nSeason 1 + 2*** (end of NH S2; 17.8m)\n2 30 / 12,469 139 / 12,498 67.2 (48.2, 80.0) 74.5 (60.0, 84.5)\n2 calendar years**** \n(end of SH S2; 23.3m)3 32 / 12,468 154 / 12,498 67.7 (52.3, 78.7) 73.3 (60.7, 82.4)\nSeason 1 –3*** \n(end of NH S3; 30.6m)4 48 / 12, 468 215 / 12,498 62.9 (46.7, 74.8) 69.1 (55.8, 78.9)\n0% 20% 40% 60% 80% 100%AReSVi- 006\nVaccine Efficacy (CI) *****\n\nCO-23\nVaccine Efficacy of Single Dose of RSVPreF3 + AS01E Against \nSevere RSV -LRTD Over 3 RSV Seasons1-4\nSeason \n(median follow -up time)RSVPreF3 + \nAS01E Placebo% VE (95% CI) *\nW/ season \ncovariateW/o season \ncovariate Number of events (n/N) \nSeason 1 (end of NH S1; 6.7m)\n1 1 / 12,466 17 / 12,494 n/a 94.1 (62.4, 99.9)\nSeason 1 + 2 (end of NH S2; 17.8.m)\n2 7 / 12,469 48 / 12,498 78.8 (52.6, 92.0) 82.7 (61.6, 93.4)\n2 calendar years (end of SH S2; 23.3m)\n3 9 / 12,468 54 / 12,498 74.9 (48.4, 89.2) 78.6 (56.3, 90.7)\nSeason 1 –3 \n(end of NH S3; 30.6m)4 15 / 12,468 75 / 12,498 67.4 (42.4, 82.7) 72.3 (51.3, 85.2)\n0% 20% 40% 60% 80% 100%\n*VE estimated using Poisson model adjusted for age, region, and season (“with season as a covariate”) or for age and region (“ without season as a covariate”; post hoc analyses). For Season only \nVE, season could not be considered a covariate, so data are presented in the “without season as a covariate” column ; CI, confidence interval; LRTD, lower respiratory tract disease; m, month; n/a, not \napplicable; NH, Northern Hemisphere; S, Season; SH, Southern Hemisphere; VE, vaccine efficacy; 1. Papi  A et al. N Engl J Med 2023; 2. Ison  MG et al. Clin Infect Dis 2024; 3. Gerber S. AREXVY \n(Adjuvanted RSVPreF3) 2 -Year Update. Presented at ACIP 26 June 2024. https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2024- 06-26-28/03- RSV- Adult- Gerber -508.pdf (accessed August \n2024); 4. Unpublished dataAReSVi- 006\nVaccine Efficacy (95% CI)\n\nCO-24\nSingle Dose of RSVPreF3 + AS01E Shows Consistent \nVaccine Efficacy for Subgroups Over 3 RSV Seasons \n*COPD, asthma, any chronic respiratory/pulmonary disease, diabetes type 1 or type 2, chronic heart failure, advanced liver or  renal disease; **97.5% CI for confirmatory secondary endpoint; 95% CI for \nother endpoints; ***Vaccine efficacy was estimated using a Poisson model adjusted for age, region, and season (“with season a s a covariate”); \nCOPD, chronic obstructive pulmonary disease; CI, confidence interval; LL, lower limit; LRTD, lower respiratory tract disease; VE, vaccine efficacy; YOA, years of age. Unpublished dataAReSVi- 006\nRSVPreF3 + \nAS01E Placebo\nNumber of events (n/N) \nLRTD 48 / 12,468 215 / 12,498\nRSV-A 14 / 12,468 80 / 12,498\nRSV-B 34 / 12,468 135 / 12,498\nSevere LRTD 15 / 12,468 75 / 12,498\n60–69 YOA 28 / 6962 117 / 6981\n70–79 YOA 15 / 4489 85 / 4489\n≥1 pre -existing comorbidity of interest*25 / 5014 116 / 4951\n≥1 cardiorespiratory condition of interest 17 / 2577 85 / 2504\n≥1 endocrine metabolic condition of interest 12 / 3243 55 / 3274\nPre-frail 12 / 4794 67 / 4779\n0% 20% 40% 60% 80% 100%\nVaccine Efficacy (CI)**,***\nConfirmatory \nsecondary \nendpoints\nVE cannot be \nreliably estimated \nfor adults \n≥ 80 YOA and frail \ngroup as too few \ncases were \nobserved\nVE with season covariateMedian Follow -up: 30.6 Months\n62.9% (46.7, 74.8)  \n69.8% (42.2, 85.7)\n58.6% (35.9, 74.1)\n67.4% (42.4, 82.7)\n60.3% (39.5, 74.8)\n70.6% (48.4, 84.3)\n64.7% (45.1, 78.1)\n68.1% (45.7, 82.3)\n63.9% (31.4, 82.5)\n70.1%  (43.9, 85.3)LL of the 2- sided CI for \nvaccine efficacy was > 20%\n\nCO-25\nVaccine Efficacy of Single Dose of RSVPreF3 + AS01E \nAgainst RSV- LRTD by RSV Season1-4\n*96.95% CI for the primary endpoint (S1 RSV -LRTD, overall); 95% CI for other endpoints; CI, confidence interval; LRTD, lower resp iratory tract disease; m, month; n/a, not applicable; NH, Northern \nHemisphere; S, Season; SH, Southern Hemisphere; VE, vaccine efficacy\n1. Papi  A et al. N Engl J Med  2023;388:595– 608; 2. Ison MG et al. Clin Infect Dis 2024;78:1732– 1744; 3. GSK. Data on File; 2024N557587_00; 4. Unpublished dataSeason \n(median follow -up time)RSVPreF3 + \nAS01E Placebo\n% VE  (CI)* Number of events (n/N) \nSeason 1 (end of NH S1; 6.7m)\n1 7 / 12,466 40 / 12,494 82.6 (57.9, 94.1)\nSeason 2 only (end of NH S2; 6.3m)\n2 20 / 4991 91 / 10,031 56.1 (28.2, 74.4)\nSeason 2 only (end of SH S2; 11.9m)\n3 22 / 4988 106 / 10,031 58.5 (33.9, 75.0)\nSeason 3 only (end of NH S3; 7m)\n4 16 / 4988 61 / 10,031 48.0 (8.7, 72.0)Vaccine Efficacy (CI)*\n0% 20% 40% 60% 80% 100%AReSVi- 006\n\nCO-26\nVaccine Efficacy of Single Dose of RSVPreF3 + AS01E Against \nRSV-LRTD in Adults with ≥ 1 Comorbidity of Interest* by RSV Season1-4\n*Conditions of interest included any chronic respiratory/pulmonary disease (including chronic obstructive pulmonary disease an d asthma) and chronic heart failure (cardiorespiratory), and diabetes \nmellitus type 1 or type 2 and advanced liver or renal disease (endocrine or metabolic); CI, confidence interval; COPD, chroni c obstructive pulmonary disease; LRTD, lower respiratory tract disease; \nm, month; NH, Northern Hemisphere; S, Season; SH, Southern Hemisphere; VE, vaccine efficacy; YOA, years of age\n1. Papi  A et al. N Engl J Med  2023;388:595– 608; 2. Ison MG et al. Clin Infect Dis 2024;78:1732– 1744; 3. GSK. Data on File; 2024N557587_00;  4. Unpublished dataSeason \n(median follow -up time)RSVPreF3 + \nAS01E Placebo\n% VE (95% CI) Number of events (n/N) \nSeason 1 (end of NH S1; 6.7m)\n1 1 / 4937 18 / 4861 94.6 (65.9, 99.9)\nSeason 2 only (end of NH S2; 6.3m)\n2 12 / 1981 48 / 3895 51.5 (7.4, 76.6)\nSeason 2 only \n(end of SH S2; 11.9m)3 13 / 1990 55 / 3916 54.2 (15.1, 77.1)\nSeason 3 only \n(end of NH S3; 7m)4 8 / 2000 37 / 3924 57.8 (8.0, 83.0)Vaccine Efficacy (95% CI)\n0% 20% 40% 60% 80% 100%AReSVi- 006\n\nCO-27\n~ 25,000 participants in pivotal efficacy trial\nCumulative follow -up occurred across all groups for median of \n31.7 months \nSafety profile of vaccine in adults ≥ 60 YOA remains acceptable \nand consistent with label1\nFrequency of SAEs/ pIMDs  remained low and similar across groups\nNo reports of GBS, ADEMSafety Profile Remains Consistent and Acceptable Over \n3 Seasons\nADEM, acute disseminated encephalomyelitis; GBS, Guillain -Barré syndrome; pIMD , potential immune -mediated disease; SAE, serious adverse event; \nYOA, years of age; 1. FDA, 2024. AREXVY Prescribing Information (PI); https://www.fda.gov/media/167805/download (URL accessed  Aug 2024)AReSVi- 006\n\nCO-28\nPublic Health Benefits with RSVPreF3 + AS01E Vaccination Over 3 Years\n71,85595,759\n020,00040,00060,00080,000100,000120,000\nRSV-LRTD Cases Averted493657\n0100200300400500600700\nRSV-related Deaths Averted+23,904 averted  +164 averted\n7,0099,340\n01,0002,0003,0004,0005,0006,0007,0008,0009,00010,000\nRSV-related Hospitalizations\nAverted+2,331 averted \nPotential RSV outcomes averted with vaccination vs no vaccination over 3 years based on 30.6- month follow up from \nStudy 006 and over 2 years based on 23.3- month follow -up from Study 006 among US adults aged 50- 59 years with COPD\nEstimated \nOutcomes \nAverted\nAssuming same vaccination coverage as influenza vaccines from 2022- 2023 season (https://www.cdc.gov/flu/fluvaxview/interactive -general -population.htm); Analysis includes 3,299,241 US adults \nwith COPD aged 50 -59 years, with 1,652,920 (50.1%) receiving RSVPreF3 + AS01E; Estimated health outcomes over 2 years based on vaccine efficacy estimates using 23.3- month follow -up data from \nRSV OA=ADJ -006 Phase 3 Trial; Estimated health outcomes over 3 years based on vaccine efficacy estimates using 30.6- month follow -up data from RSV OA=ADJ -006 Phase 3 Trial\n\nCO-29\nOverview of Clinical Development Program\n\nCO-30\nOverview of Clinical DevelopmentCo-administration\nSafety, reactogenicity, and Immunogenicity \nRSV OA=ADJ -011 study\n(Extension of Study 002)\nAdults  ≥ 60 YOA\nPersistence and safety and immunogenicity of \na re-vaccination doseRSV OA=ADJ -002 study\nAdults 18– 40 or 60– 80 YOA\nFirst-in-human safety, immunogenicity, \nformulation, and dosing selectionAReSVi -006 study\nAdults  ≥ 60 YOA\nPivotal efficacy study\nAReSVi -004 study\nAdults  ≥ 60 YOA\nSafety, reactogenicity, immunogenicity, \npersistence, and re- vaccination\nRSV OA=ADJ -023 study\nImmunocompromised adults ≥ 18 YOA \n(lung and kidney transplant recipients)\nSafety and immunogenicity\nPhase 1/2 Phase 2b Phase 3\nCompletedOngoing/in progress/\ndata not yet public\nRSV OA=ADJ -017 study\nAdults ≥ 65 YOA\nCo-administration with FLU -aQIV\nRSV OA=ADJ -007 study\nAdults ≥ 60 YOA\nCo-administration with FLU -QIV\nRSV OA=ADJ -008 study\nAdults  ≥ 65 YOA\nCo-administration with FLU -QIV-HD\nRSV OA=ADJ -018 study\nAdults 50−59 YOA (incl. adults at\nincreased risk of RSV -LRTD) vs ≥ 60 YOA\nSafety, reactogenicity, immunogenicity\nRSV OA=ADJ -025 study\nAdults 18– 49 YOA at increased risk \nvs adults ≥ 60 YOA\nImmunogenicity and safety\nRSV OA=ADJ -012 study\n(Extension of Study 006) \nExtension & crossover study \nin adults ≥ 60 YOA\nImmunogenicity and safety of different \nre-vaccination schedules and persistence of \nsingle dose\nRSV OA=ADJ -020 study\nAdults  ≥ 50 YOA\nCo-administration with HZ/ su vaccine\nFLU-aQIV : adjuvanted quadrivalent influenza vaccine; FLU -QIV: quadrivalent influenza vaccine; FLU -QIV-HD: high -dose quadrivalent influen za vaccine; HZ/ su: herpes zoster recombinant subunit; \nM: month; PCV20, 20 -valent pneumococcal conjugate vaccine; RSV -LRTD: respiratory syncytial virus lower respiratory tract disease; YOA: years of age \nAll studies ClinicalTrials.gov; All URLs accessed October 2024\nRSV OA=ADJ -019 study\nAdults  ≥ 60 YOA\nCo-administration with PCV20\nRSV OA=ADJ -013 study\n Adults ≥ 50 YOA\nCo-administration with \nCOVID -19 mRNA vaccine\n\nCO-31\nSummary\n\nCO-32\nConclusions\nFor solid organ transplant recipients on mycophenolate, a second dose of RSVPreF3 + AS01E \nresulted in RSV -A and RSV -B neutralizing antibody responses close to levels observed in adults \n≥ 50 YOA at same time pointOne dose of RSVPreF3 + AS01E provides robust RSV -A and RSV -B neutralizing antibody \nresponses and high CD4+ T -cell responses; acceptable safety profile in kidney and lung \ntransplant recipients ≥ 18 YOA\n1\nAhead of this year’s RSV season, it is important to protect vulnerable individuals ≥ 50 YOA who \nare at high-risk for severe RSV disease RSVPreF3 + AS01E provides clinically meaningful efficacy over 3 seasons \n(median follow up time 30.6 months) in ≥ 60 YOA, with a continued acceptable safety profile\nEstimated public health benefits of RSVPreF3 + AS01E are increased given its efficacy \nover 3 seasons as compared to previous efficacy estimates\n2\n3\n4\n5\n\nCO-33\nMeeting of the Advisory Committee on \nImmunization Practices (ACIP)\nCenters for Disease Control and Prevention\nOctober 24, 2024\nSusan Gerber, MD\nMedical Director \nGSK\nPresentation by GSK at ACIP October 24, 2024", "summary": "CO-1 Meeting of the Advisory Committee on  Immunization Practices (ACIP) Centers for Disease Control and Prevention October 24, 2024 Susan Gerber, MD Medical Director  GSK Presentation by GSK at ACIP October 24, 2024  CO-2 ~ 9 million AREXVY doses administered in US to dateAREXVY Indications  AREXVY is indicated for active immunization for prevention of lower respiratory  tract disease (LRTD) caused by RSV in Individuals ≥ 60 YOA Individuals 50-59 YOA at increased risk for LRTD caused by…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-23-24-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/04-RSV-Adult-Gerber-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 33}
{"title": "05 RSV Adult Lloyd 508", "content": "1\nEvaluation of Guillain -Barré Syndrome (GBS) \nfollowing Respiratory Syncytial Virus (RSV) \nVaccination Among Adults 65 Years and Older\n \nDr. Patricia Lloyd, ScM PhD\nHealth Statistician\nOffice of Biostatistics and Pharmacovigilance\nCenter for Biologics Evaluation and Research\nU. S. Food & Drug Administration\nMEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)\nRespiratory Syncytial Virus (RSV) Vaccine, Adults \nOctober 23 -24, 2024\n2\nOutline\n•Introduction\n•Presentation of End -of-Season SCCS Analysis Results and \nComparison to Early -Season Results\n•Discussion\n•Conclusions\n3\nIntroduction\n•Three RSV vaccines were approved for use in the U.S. in adults 60 years and \nolder\n▪RSVPreF3+AS01 (GSK – AREXVY®) – May 3, 2023\n▪RSVPreF  (Pfizer – ABRYSVO®) – May 31, 2023\n▪mRNA -1345 (Moderna – mRESVIA®) – May 31, 2024*\n•Pre-licensure clinical trials identified a small number of GBS cases in \nRSVPreF3+AS01 and RSVPreF  vaccines\n•Reports submitted to Vaccine Adverse Events Reporting System (VAERS) \nidentified higher GBS rates post -RSVPreF3+AS01 and RSVPreF  vaccination than \nexpected background rates\n* The analyses described in this presentation included vaccinations through Jan 2024, which was prior to the approval of mRNA -1345 vaccine\n4\nRSV Vaccine Post -Market Analyses\nAnalysesIncludes Vaccines \nAdministered \nThroughData \nThrough \nDateNumber of DosesNumber \nGBS \nCases RSV PreF3+AS01 RSVPreF\nEarly -Season SCCS October 22, 2023 April 6, 2024 872,068 456,107 28\nEnd-of-Season SCCS January 28, 2024 July 13, 2024 2,202,247 1,024,442  95•Post-market analyses* to assess the safety of RSV vaccines among Medicare \nFee-for-Service (FFS) beneficiaries ages 65 and older\n* The analyses described in this presentation included vaccinations through Jan 2024, which was prior to the approval of mRNA -1345 vaccine.\n5\nSelf-Controlled Case Series (SCCS) Design\nDays 43 -90 Days 1 -42\n365 Days Prior\nStudy Start Date\nMay 2023End-of-Season\nStudy End Date\nJuly 2024\nRSV Vaccination (Day 0)\n* The clean window is relative to the outcome date; risk and control intervals are relative to the vaccination date\nƗ Incident GBS identified in inpatient – primary position only; ICD -10-CM DGN G61.0= Risk Interval\n= Control Interval\n= GBS Outcome Ɨ= Clean Window (365 days)*\nGBS Outcomes \nObserved Through\nApr 2024Vaccinations \nthrough\nJan 2024\n\n6\nSCCS Analysis: Study Methods\nStudy Design Self-Controlled Case Series (SCCS)\nData Sources\n/Study \nPopulation•Medicare Fee -for-Service (FFS) (Parts A, B and D) beneficiaries aged 65 years and older \n•Enrolled  on date of first observed RSV vaccination and during 1 -year prior to vaccination\n•Incident GBS case during the observation period (i.e., no GBS event in the clean window)\n•Vaccinated with either RSVPreF3+AS01 or RSVPreF prior to Jan 28, 2024\nStudy Period May 2023 – Jul 2024\nGBS Outcome \nDefinition•Risk Interval: 1 - 42 days\n•Control Interval: 43 - 90 days\n•Care Setting: inpatient – primary position only; ICD -10-CM DGN G61.0\nStatistical \nAnalyses•Incidence Rate Ratios (IRR)\n•Absolute Risk: Attributable Risk (AR) per 100,000 doses and 100,000 person -years (PY)\n•Adjustment for outcome -dependent observation time (Farrington), seasonality, PPV\n•Chart -confirmed analysis with Farrington and seasonality adjustments \n•Secondary analyses: IRR, AR stratified by same day concomitant vaccination with 2023 -2024 \nCOVID -19, 2023 -2024 influenza, pneumococcal, and shingles vaccines\nStudy end date for End of Season SCCS analysis was July 13, 2024\nNote: RSV vaccinations observed prior to Jan 28, 2024 were needed for 90% complete observation in 90 days post vaccination\n7\nEnd-of-Season SCCS Analysis\nWeekly  Uptake Trends in for RSVPreF3+AS01 and RSVPreF  Vaccines   \n020,00040,00060,00080,000100,000120,000140,000160,000\nJul-23 Aug-23 Sep-23 Oct-23 Nov-23 Dec-23 Jan-24 Feb-24 Mar-24 Apr-24 May-24 Jun-24Number of RSV Vaccinations\nCalendar WeekRSVPreF3+AS01\nRSVPreFEnd-of-Season \nVaccination \nCutoff  Date 01/28/2024\nEnd of 90 -day \nobservation \nperiod from \ncutoff dateAdditional \n11 weeks \nfor 90% \ncomplete \nclaimsEarly -Season \nVaccination \nCutoff Date 10/22/2023\nData Through Date: July 13, 2024\n8\nSCCS Analysis: Descriptive Results\nCase Counts for GBS following RSV vaccination by Vaccine Type    \n*n = Medicare beneficiaries that received one RSV vaccination and eligible for early - and end -of-season SCCS analysis are presen ted. Product -specific and total dose counts \nmay not equal due to rounding\nƗ Cell suppressed to protect patient confidentialityCase Population Eligibility \nCriteriaEarly -Season SCCS Analysis End-of-Season SCCS Analysis\nRSV Vaccinations \n(n = 1.3 M doses)*RSV Vaccinations \n(n = 3.2 M doses)*\nRSVPreF3+AS01\n(n = ~872k doses)*RSVPreF\n(n = ~456k doses)*RSVPreF3+AS01\n(n = 2.2 M doses)*RSVPreF\n(n = 1.0 M doses)*\nTotal GBS cases [total number of \ndays in study period]160 [339 days] 92 [311 days] 236 [437 days] 130 [409 days]\nGBS cases  during 90 -day \nobservation period 105 74 119 89\nIncident GBS cases after applying \nclean window restriction55 36 <70 <50\nGBS cases qualifying for SCCS \nanalyses11 17 56 39\nEarly -Season Data Through Date: April 6, 2024\nEnd-of-Season Data Through Date: July 13, 2024\n9\nGBS Medical Record Review (MRR) Results   \nGBS MRR Overall\nTotal GBS Cases and Records Requested 95\nRecords Received and Adjudicated 75\nChart -Confirmed GBS Cases* (Level 1, Level 2, Level 3) 51\nInsufficient Evidence or Not a Case* (Level 4, Level 5) 24\nRecords Not Returned 20\nCategory PPV** with 95% Confidence Interval (CI)\nOverall 68.0% (56.8%, 77.5%)\nRisk Interval 62.3% (48.8%, 74.1%)\nControl Interval 81.8% (61.5%, 92.7%)\n** PPV calculations include all GBS case records assigned a case classification based on the MRR in the denominatorCase Classification of GBS Medical Records\nPositive Predictive Value (PPV) of GBS* Medical records were adjudicated per the Brighton Collaboration clinical case definition for GBS\n10\n SCCS analyses including most adjustments are highlighted in red\nFarrington -Adjusted Analysis = Outcome -Dependent Observation Time Adjustment A statistically significant elevation in GBS risk was observed with \nseasonality, Farrington, PPV adjusted analysis that included chart -confirmed and non -returned cases:\nRSVPreF3+AS01\n2.46 (95% CI: 1.19, 5.08)\nComparison of Early vs. End of Season Results \nGBS and RSVPreF3+AS01\nIncidence Rate Ratio (IRR) with 95% Confidence Intervals (95% CI)\n11\n SCCS analyses including most adjustments are highlighted in red\nFarrington -Adjusted Analysis = Outcome -Dependent Observation Time Adjustment An elevated but non -statistically significant IRR was observed for GBS\nwith seasonality, Farrington, PPV adjusted analysis that included chart -confirmed and non -returned cases:\nRSVPreF\n2.02 (95% CI: 0.93, 4.40)\nComparison of Early vs. End of Season Results \nGBS and RSVPreF\nIRR with 95% CI\n12\nSeasonality, Farrington Analysis, and PPV -Based Multiple Imputation – Chart Confirmed + Not Returned \nCases\nInferential Analysis Results RSVPreF3+AS01 RSVPreF\nEligible Vaccines 2,202,247 1,024,442\n*Cases in the Risk Interval 24 18\n*Cases in the Control Interval 11 <11\nIRR (95% CI) 2.46 (1.19, 5.08) 2.02 (0.93, 4.40)\nAR per 100,000 Doses (95% CI) 0.65 (0.18, 1.12) 0.90 ( -0.02, 1.81)\nAR Per 100,000 PY (95% CI) 5.71 (1.61, 9.80) 7.82 ( -0.17, 15.81)\nPY = Person -YearsEnd-of-Season SCCS Results: GBS and RSV Vaccination\nIRR and Attributable Risk (AR) \n*Cases in risk and control intervals are the average number of true cases in the multiple imputation process\nSmall cell sizes <11; suppressed to protect patient confidentiality \n13\nRSVPreF3+AS01 RSVPreF\nEligible Vaccines 2,202,247 1,024,442\nTotal GBS Cases 56 39\nNumber (%) with any concomitant \nvaccination20 (35.7%) 19 (48.7%)End-of-Season Descriptive Results: \nConcomitant Vaccination among GBS Cases\nConcomitant vaccination is defined as vaccination on the same day as RSV vaccination with at least one of \n2023 -2024 COVID -19, 2023 -2024 influenza, pneumococcal, and shingles vaccines.\n14\nSeasonality and Farrington Adjusted Analysis, All CasesSecondary End -of-Season SCCS Results: \nGBS risk by vaccine type and concomitant vaccination\nIRR and 95% CI\nThere was no evidence of difference in GBS risk among persons with and without same day concomitant \nvaccination with RSV vaccines\n15\nSeasonality and Farrington Adjusted Analysis \nInferential Analysis ResultsWith Concomitant \nVaccinationWithout Concomitant \nVaccination\nEligible Vaccines 833,067 1,369,180\nCases in the Risk Interval <15 <30\nCases in the Control Interval <11 <11\nIRR (95% CI) 2.19 (0.87, 5.49) 3.47 (1.61, 7.46)\nAR per 100,000 Doses (95% CI) 0.85 ( -0.09, 1.79) 1.40 (0.72, 2.09)\nAR Per 100,000 PY* (95% CI) 7.40 ( -0.79, 15.59) 12.27 (6.26, 18.28)\n*PY = Person -YearsSecondary End -of-Season SCCS Results: \nConcomitant Vaccination among GBS cases vaccinated \nwith RSVPreF3+AS01 – IRR and AR\nSmall cell sizes <11; suppressed to protect patient confidentiality \n16\nSeasonality and Farrington Adjusted Analysis\nInferential Analysis ResultsWith Concomitant \nVaccinationWithout Concomitant \nVaccination\nEligible Vaccines 420,764 603,678\nCases in the Risk Interval <15 <20\nCases in the Control Interval <11 <11\nIRR (95% CI) 2.26 (0.89, 5.73) 4.48 (1.50, 13.42)\nAR per 100,000 Doses (95% CI) 1.59 ( -0.18, 3.35) 2.06 (0.99, 3.12)\nAR Per 100,000 PY* (95% CI) 13.85 ( -1.55, 29.25) 18.01 (8.70, 27.31)Secondary End -of-Season SCCS Results: \nConcomitant Vaccination among GBS cases vaccinated \nwith RSVPreF  – IRR and AR\n*PY = Person -YearsSmall cell sizes <11; suppressed to protect patient confidentiality \n17\nSCCS Design: Strengths and Limitations\nStrengths Limitations\n•SCCS study design provides robust \nadjustment for potential time -\ninvariant confounding\n•Large database facilitates more \nprecise evaluation of GBS\n•Study findings are generalizable to \nU.S. population 65 years and older\n•Medical Record Review improved \nclassification of GBS•Potential misclassification of GBS in \nadministrative claims data\n•The study is not intended to compare \nGBS risk between the two vaccine \nproducts\n•IRR estimates may be sensitive to the \nnumber of records returned and \nadjudicated through MRR\n•Potential misspecification of post -RSV \nvaccination risk and control intervals for \nGBS\n•Potential for residual confounding\n•Attributable risk based on small number \nof cases may be difficult to interpret\n18\nDiscussion\n•Observed vs. Expected Analysis\n▪An elevated risk of GBS was observed following both RSV vaccines \n▪Results were not statistically significant for RSVPreF3+AS01 when adjusting for PPV\n•Early -Season SCCS\n▪Statistically significant elevation in GBS risk was observed following RSVPreF  vaccine\n▪Results did not remain statistically significant for RSVPreF  vaccine when adjusting for PPV -\nbased multiple imputations\n•End-of-Season SCCS\n▪A statistically significant elevated IRR was observed for GBS following vaccination with \nRSVPreF3+AS01; GBS risk was elevated yet not statistically significant following RSVPreF  \nvaccination\n▪Results remained the same when restricting to confirmed GBS cases through MRR\n▪There was no evidence of difference in GBS risk among persons with and without same day \nconcomitant vaccination with RSV vaccines\n19\nConclusions\n•Our findings suggest an increased GBS risk following RSVPreF 3+AS01  and \nRSVPreF  among adults aged 65 years and older\n•These results are consistent with pre -licensure clinical trials and surveillance \nsystems such as VAERS\n•End-of-season SCCS analyses  results are largely chart -confirmed from MRR \nand include approximately three times more vaccine doses and GBS cases \ncompared to the early season SCCS results \n•GBS risk following vaccination with RSVPreF3+AS01 and RSVPreF  is rare, with \nless than 10 cases per 1 million vaccinations\n•There is no difference in GBS risk among persons with and without same \nday concomitant vaccination with RSV vaccines\nReferences\n20\n1. Respiratory Syncytial Virus Vaccine Recombinant, Adjuvanted ( Arexvy ). Vaccines and Related Biological Products Advisory \nCommittee Meeting. FDA Briefing Document. March 1, 2023. https://www.fda.gov/media/165622/download\n2. Respiratory Syncytial Virus Stabilized Bivalent Prefusion F Subunit Vaccine ( Abrysvo ). Vaccines and Related Biological Products \nAdvisory Committee Meeting. FDA Briefing Document. March 1, 2023. https://www.fda.gov/media/165625/download\n3. Hause  AM, M.P., Baggs  J, et al, , Early Safety Findings Among Persons Aged ≥60 Years Who Received a Respiratory Syncytial \nVirus Vaccine — United States. 2024, Centers for Disease Control and Prevention (CDC),: MMWR and Morbidity and Mortality \nWeekly Report.\n4. Petersen I, Douglas I, Whitaker H. Self controlled case series methods: an alternative to standard epidemiological study desi gns. \n2016;354:i4515.\n5. Evaluation of Multiple Safety Outcomes following Respiratory Syncytial Virus (RSV) Vaccination in Adults 60 Years and Older. \nBEST Initiative. Center for Biologics Evaluation and Research (CBER). United States Food and Drug Administration (U.S. FDA). \nhttps://bestinitiative.org/wp -content/uploads/2024/01/BEST_RSV_Safety_Older_Adults_2023 -2024.pdf\n6. Sejvar  JJ, Kohl KS, et al, Guillain –Barré syndrome and Fisher syndrome: Case definitions and guidelines for collection, analysis, \nand presentation of immunization safety data, Vaccine, Volume 29, Issue 3, 2011. https://doi.org/10.1016/j.vaccine.2010.06.003 .\n7. Farrington, C. P., Anaya -Izquierdo, K., Whitaker, H. J., Hocine , M. N., Douglas, I., & Smeeth, L. (2011). Self -Controlled Case \nSeries Analysis With Event -Dependent Observation Periods. Journal of the American Statistical Association, 106(494), 417 –426. \nhttps://doi.org/10.1198/jasa.2011.ap10108 \n8. Arya, D.P., et al. Surveillance for Guillain -Barré syndrome after 2015 -2016 and 2016 -2017 influenza vaccination of Medicare \nbeneficiaries. Vaccine, 2019. 37(43): p. 6543 -6549.\nAcknowledgements\n21\nU.S. Food and Drug Administration\nSteven A. Anderson\nRichard A. Forshee\nHenry T. Zhang\nNarayan Nair\nKrista Fekecs\nAcumen\nPurva Shah \nNimesh Shah\nZhiruo Wan \nMao Hu \nMeng Chen \nCenters for Medicare & Medicaid ServicesJing Wang\nYue Wu \nYoganand Chillarige \nAcumen’s Physician TeamJoann F. Gruber\nTainya C. Clarke", "summary": "1 Evaluation of Guillain -Barré Syndrome (GBS)  following Respiratory Syncytial Virus (RSV)  Vaccination Among Adults 65 Years and Older   Dr. Patricia Lloyd, ScM PhD Health Statistician Office of Biostatistics and Pharmacovigilance Center for Biologics Evaluation and Research U. S. Food & Drug Administration MEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP) Respiratory Syncytial Virus (RSV) Vaccine, Adults  October 23 -24, 2024 2 Outline •Introduction •Presentation of End…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-23-24-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/05-RSV-Adult-Lloyd-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 21}
{"title": "04 Schillie mening 508", "content": "Introduction to MenQuadfi Label Change for \nInfants\nSarah Schillie, MD, MPH, MBA\nAdvisory Committee on Immunization Practices\nApril 16, 2025National Center for Immunization & Respiratory Diseases\n1\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position o f \nthe U. S. Centers for Disease Control and Prevention.\nMenACWY Vaccines Available for Use in the \nUnited States*\nManufacturer Trade Name AbbreviationLicensed \nAge GroupACIP \nRecommended \nAge Group*\nSanofi Pasteur Menactra MenACWY -D9 months –55 \nyears≥9 months\nSanofi Pasteur MenQuadfi MenACWY -TT ≥2 years ≥2 years\nGlaxoSmithKline Menveo MenACWY -CRM2 months –55 \nyears≥2 months **\n*Same product preferred, but not required, for all doses in a series\n**Includes off -label recommendations for persons 56 years and older2 of 6\nMenACWY Vaccine Recommendations*\nRoutinely recommended for persons at age 11–12 years and \n16 years\nRecommended for persons aged ≥2 months with risk factors:\n–Complement component deficiencies or complement inhibitor use\n–Anatomic or functional asplenia\n–HIV infection\n–Microbiologists routinely exposed to N. meningitidis isolates \n–Persons at increased risk during an outbreak\n–Persons who live in or travel to countries in which meningococcal disease is \nhyperendemic or epidemic \n*Mbaeyi SA, Bozio CH, Duffy J, et al. Meningococcal Vaccination: Recommendations of the Advisory Committee on Immunization \nPractices, United States, 2020. MMWR Recomm Rep 2020;69(No. RR -9):1– 41. DOI: http://dx.doi.org/10.15585/mmwr.rr6909a1 .\n3 of 6\nMenACWY Vaccine Recommendations\nfor Persons with Risk Factors*\n<2 Years:\n–Age 2 months:  4 -dose series (2, 4, 6, 12 mos)\n–Age 3 –6 months:  3 - or 4- dose series (dose 2 [and dose 3 if applicable] ≥8 wks after \nprevious dose until a dose is received at age ≥7 mos, followed by an additional dose \n≥12 wks later and at age >12 mos)\n–Age 7 –23 months:  2- dose series (dose 2 ≥12 wks after dose 1 and at age >12 mos)\n≥2 Years:  2 -dose primary series, with doses separated by 8 wks**\nBooster dose:\n–Age <7 years:  3 yrs after primary series and every 5 yrs thereafter \n–Age ≥7 years:  5 yrs after primary series and every 5 yrs thereafter\n            *Mbaeyi SA, Bozio CH, Duffy J, et al. Meningococcal Vaccination: Recommendations of the Advisory Committee on Immunization \nPractices, United States, 2020. MMWR Recomm Rep 2020;69(No. RR -9):1– 41. DOI: http://dx.doi.org/10.15585/mmwr.rr6909a1 .\n**Medical risk factors4 of 6\nMenQuadfi Proposed Licensure in Infants\nWith discontinuation of Menactra, Menveo is the only \nMenACWY vaccine available in the United States for persons under 2 years of age\nSanofi Pasteur seeking infant indication for MenQuadfi for the following ages at initiation (anticipated May 2025):\n–6 weeks –5 months:  2, 4, 6, 12– 18 months (first dose may be administered as \nearly as 6 weeks) \n–6–23 months:  2- dose series with 2nd dose administered in second year of life \nand ≥3 months after 1st dose\n–≥2 years:  1 dose\n5 of 6\n6Acknowledgements\nLucy McNamara\nAvnika Amin\nAmy Rubis\nSusan Hariri\nNoele Nelson\nLeAnne Fox\nAlison Albert\n6 of 6", "summary": "Introduction to MenQuadfi Label Change for  Infants Sarah Schillie, MD, MPH, MBA Advisory Committee on Immunization Practices April 16, 2025National Center for Immunization & Respiratory Diseases 1 The findings and conclusions in this report are those of the authors and do not necessarily represent the official position o f  the U. S. Centers for Disease Control and Prevention. MenACWY Vaccines Available for Use in the  United States* Manufacturer Trade Name AbbreviationLicensed  Age…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/04-Schillie-mening-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 6}
{"title": "05 Dawson Mening 508", "content": "FOR USE ONLY BY SANOFI MEDICAL AFFAIRS FOR SCIENTIFIC EXCHANGE PURPOSES. DO NOT COPY OR DISTRIBUTEMAT-US-2204183 -R -NONDISTRIB -EXP 7/3/26\nMeningococcal \n(Groups A, C, Y, \nandW) Conjugate \nVaccine ( MenQuadfi®)\nExtension of use to include \ninfants from 6 weeks of age\n\nAgenda\nPublic health \nburden of invasive \nmeningococcal \ndiseaseRationale for clinical \ndevelopmentClinical data from \ninfant studiesSummary\n2\nPublic health burden of meningococcal disease \n•Meningococcal disease remains a major global health challenge because it can strike quickly \nand with devastating effect, taking a life in < 24 hours 1,2\n•Case-fatality rate is ~10% to 15% even with appropriate treatment2 \n•~1 in 5 survivors suffer permanent sequelae3,4\n•Since introduction of the first MenACWY  conjugate vaccine in 2005, MenACWY -D, IMD \ncaused by serogroups C, W, and Y has declined by > 90% among adolescents and young adults5\n•Infants continue to have the highest incidence of IMD, so we would like to share \ninformation about the performance of Sanofi's MenACYW -TT in this population\n1. Thompson MJ, et al. Lancet . 2006;367(9508):397- 403. 2. WHO. https://www.who.int/en/news -room/fact -sheets/detail/meningococcal -meningitis  [accessed March 2020]. 3. CDC. \nMMWR . 2013;62(RR -2):1-22. 4. Rosenstein NE, et al. N Engl J Med. 2001;344(18):1378- 1388. 5. MacNeil JR, et al . Clin Infect Dis  2018; 66:1276– 81.\nLimb amputation\n Deafness\n Brain damage3\nWhat is MenQuadfi (MenACYW -TT)?\n•A quadrivalent meningococcal conjugate vaccine to help prevent invasive meningococcal disease \ncaused by serogroups A, C, W, and Y\n•FDA approved on 23 April 2020 for use in persons 2 years of age and older\n•Developed with the ambition of being: \n•Used across a broad age range\noStudies to support expansion of age indication to include infants as young as 6 weeks of age are \ncompleted\n•Incorporated in various immunization schedules that exist worldwide \n•Conjugated to tetanus toxoid (approximately 55 µg)\n•Each 0.5 -mL intramuscular dose contains 10 µg each of the 4 meningococcal \npolysaccharides\n•Fully liquid solution that does not require reconstitution and supplied in a single -dose vial4\nAge at First Dose Primary Vaccination Schedule\nInfants aged from 6 weeks 4-dose series at 2, 4, 6 and between 12 \nand 18 months of age. The first dose may \nbe given as early as 6 weeks.\nInfants aged 6 months through 23 months 2-dose series with the second dose \nadministered in the second year of life and at least 3 months after the first dose.\nIndividuals 2 years of age and older A single doseProposed Schedule for Primary Vaccination with MenACYW -TT5\nOverview of MenQuadfi \nClinical Development\nToddlers\n(12–23 Months)\nInfants\n(6 Weeks –11 Months)\nMET42\nPhase III\nSchedule: 3+1 (2, 4, 6, 12– 18M)\nControl MenACWY -CRM\nUSA\nNCT03537508MET58\nPhase III\nSchedule: 2+1 (2, 4, 12– 18M)\nand 3+1 (2, 4, 6, 12– 18M)\nControl MCV4 -TT\nEurope*\nNCT03547271MET52\nPhase III\nSchedule: 1+1 (3, 12– 13M)\nNI when co -ad MenB  and\nstandard of care vaccines§\n(multi -dose)\nUK\nNCT03632720\nMET61\nPhase III\nSchedule: 1+1 (6M+)\nControls MenACWY -CRM, MenACWY -D \nUSA\nNCT03691610MET41\nPhase III\nSchedule: 3+1 (2, 4, 6, 12M)\nControl MenACWY -CRM\nUSA\nNCT03673462MET33\nPhase III\nSchedule: 2+1 (2 or 3, 6, 12M) \nControl MenACWY -CRM in 3 +1 \n(2, 4, 6, 12M) \nRussia, Mexico\nNCT03630705\nMEQ00089\nPhase III\nSchedule: 1+1 (6M+): 6- 7 +12- 13 M \nControl: MCV4 -TT\nEU \nONGOINGMEQ00065\nPhase III\nNI / Superiority \nControls MenC -conj and MCV4 -TT\n(single -dose)\nDenmark, Finland, Germany\nNCT03890367\nMEQ00086\nInterchangeability\nToddlers (12−23M) \nToddlers primed with MenACWY -CRM or MCV4 -TTduring \n1Y \nArgentina  \nONGOINGToddlers\n(12–23 Month s)\nMET54\nPhase II\nControl MCV4 -TT\n(single dose )\nFinland\nNCT03205358\nMET51\nPhase III\nControl: MCV4 -TT\n(single dose )\nGermany, Spain, \nFinland, Hungary\nNCT02955797\nMET57\nPhase III\nSingle dose co -ad* with MMR + varicella, DTaP -IPV-\nHB-Hib, or PCV13 (single dose)\nNo Meninge vaccine control\nSouth Korea, Russia, Mexico, Thailand\nNCT03205371MenQuadfi \nClinical \nDevelopment \nProgram in \nInfants and \nToddlers\n  Coadministration study\n  Booster dose study\nMenACWY -TT = MenQuadfi , MenACWY -CRM = Menveo, MenACWY -D = Menactra , MCV4 -TT= Nimenrix  (not licensed in US)\n-Studies in green font are completed\n-Studies in black font are ongoing7\n&\nMET42\nImmunogenicity and Safety \nStudy of a Quadrivalent \nMeningococcal Conjugate \nVaccine (MenACYW -TT) when \nCo-administered with Routine \nPediatric Vaccines in Healthy \nInfants and Toddlers in the US \nand Puerto Rico\nShort Study Title Immune Non -inferiority, Safety and Co -\nadministration study in infants  & toddlers\nStudy PopulationAge group ≥ 42 to ≤ 89 days\nNumber of \nparticipants2627\nMeningococcal -vaccine naïve \nVaccine GroupsGroup 1: MenACYW -TT + Routine pediatric vaccines\nGroup 2: MenACWY -CRM + Routine pediatric \nvaccines\nVaccination ScheduleSingle dose of MenACYW -TT or MenACWY -CRM (2, \n4, 6, and 12 months )\nSafety follow upImmediate \nUnsolicited \nSystemic \nAEsWithin 30 minutes after each vaccination\nSolicited \nAEsDay 0 toDay 7 after each vaccination\nUnsolicited \nAEsD0 to D30 after each vaccination\nSAEs \n(AESIs and \nMAAEs)Visit1 (day of firstvaccination) untiltheendof the\n6-month follow -up period after thelastvaccination.MET42: Study design and demographic data9\nBaseline CharacteristicsGroup  1\n(N=1746)Group  2\n(N=881)\nSex: n (%)\nMale 918 (52.6) 466 (52.9)\nFemale 828 (47.4) 415 (47.1)\nSex ratio: Male/Female 1.11 1.12\nAge: (Days)\nMean  (SD) 65.3 (8.02) 65.3 (7.81)\nMin ; Max 42.0 ; 89.0 42.0 ; 89.0\nMedian 64.0 64.0\nRacial  origin:  n (%)\nAmerican Indian or Alaska  \nNative 11 (0.6) 3 (0.3)\nAsian 15 (0.9) 10 (1.1)\nBlack or African American 204 (11.7) 99 (11.2)\nNative  Hawaiian  or Other  Pacific  \nIslander7 (0.4) 6 (0.7)\nWhite 1428 (81.8) 722 (82.0)\nMixed  Origin 44 (2.5) 30 (3.4)\nUnknown 19 (1.1) 6 (0.7)\nEthnicity:  n (%)\nHispanic or Latino 838 (48.0) 410 (46.5)\nNot Hispanic or Latino 897 (51.4) 465 (52.8)\nUnknown 3 (0.2) 4 (0.5)\nNot reported 8 (0.5) 2 (0.2)\nImmunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine When Administered Concomitantly With Routine Pediatric  Vaccines in Healthy Infants and Toddlers in the \nUS. ClinicalTrials.gov , Sanofi Pasteur, 15 Oct. 2024, https://clinicaltrials.gov/study/NCT03537508  \nAESI: Adverse events of special interest, MAAE: Medically attended adverse events. \nMET42\nSafety\n\n24.126.6 28.4 29.833.2 34.7\n13.6 13.619.6 18.927.330.134.433.825.528.6 20.220\n9.57.512 14.212.712.911.811.4\n8.56.5\n66.4\n1.11.21.72.12.93.4\n0102030405060708090100\nCrying abnormal Drowsiness Vomitting Fever Apetite lostGrade 1\nGrade 2\nGrade 3\nGroup 1: MenACYW -TT and routine pediatric  vaccines; Group 2: MenACWY -CRM and routine pediatric  vaccinesMET42: Solicited injection site & systemic reactions within 7 days after \nany dose  11\nInjection site Reactions\nTenderness was the most frequently reported solicited injection \nsite reaction. Erythema and swelling were reactions less \nfrequently experienced. Most solicited injection site reactions were \nof Grade 1 or 2 intensity.Irritability was the most frequently reported solicited systemic \nreaction, followed by crying abnormal, drowsiness & appetite lost. \nFever (33.4% vs 35.2%) and vomiting were reactions less frequently \nexperienced. Most solicited systemic reactions were of Grade 1 or 2 \nintensity\nImmunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine When Administered Concomitantly With Routine Pediatric  Vaccines in Healthy Infants and Toddlers in the \nUS. ClinicalTrials.gov, Sanofi Pasteur, 15 Oct. 2024, https://clinicaltrials.gov/study/NCT03537508  Systemic Reactions\nIrritability Crying abnormal Drowsiness Vomiting Fever34.5 35.332.1 30.9\n23.5 21.823.6 23.6\n11.7\n0.91.29.1 8.7\n0.20.5\n0.20.4\n0102030405060708090100\nGROUP 1 GROUP 2 GROUP 1 GROUP 2 GROUP 1 GROUP 2\nERYTHEMA SWELLINGGrade 1\nGrade 2\nGrade 3\nTenderness Erythema SwellingAppetite \nlostGroup  1Group 2 Group 2 Group 2 Group 2 Group  2 Group  2 Group 1 Group 1 Group 1 Group 1 Group  1Percentage of participants\nPercentage of participants\nMET42: Summary of results\nSummary of SAEs, AESIs and unsolicited AEs after any vaccine injections\nAESI: adverse events of special interest 99 subjects (5.7%) in Group 1 ( MenACYW -TT), 38 subjects (4.4%) in Group 2 ( MenACWY -CRM) reported SAEs during the study\n18 subjects reported AESI during the study: 13 subjects (0.8%) in Group 1 ( MenACYW -TT) and 5 (0.6%) subjects in Group 2 \n(MenACWY -CRM)\nThere were 2 subjects (both in Group 1- MenACYW -TT) who discontinued due to SAEs ( Infantile spasms, Cardiac arrest )•2 subjects reported SAEs related to study vaccines during the study:\n1 instance of febrile seizure in a participant in Group 1 ( MenACYW -TT) with prior history of seizures. The Febrile seizure was \nan AESI (13 days after 15 -month dose)\n1 subject reported fever post vaccination in Group 2 ( MenACWY -CRM) (8 hours following 2 -month dose)\n•All AESIs were nonrelated to the study vaccines, except the one SAE mentioned above\n•There was one death reported in the study. It was deemed unrelated to the study vaccine by the investigator and sponsor\nImmunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine When Administered Concomitantly With Routine Pediatric  Vaccines in Healthy Infants and Toddlers in the \nUS. ClinicalTrials.gov, Sanofi Pasteur, 15 Oct. 2024, https://clinicaltrials.gov/study/NCT03537508  12\nMET42\nImmunogenicity\n\n95% CI of the single proportion calculated from the exact binomial method. \nGroup 1a: MenACYW -TT and routine vaccines at 2, 4, 6, and 12 to 15 months of age\nGroup 2a: MenACWY -CRM at 2, 4, 6, and 12 months of age and routine vaccines at 2, 4, 6, 12, and 15 \nto 18 months of ageVaccine seroresponse * at day 30 after the booster dose (Group 1 vs Group 2) in Per -protocol Analysis Set \n*hSBA  vaccine seroresponse  for serogroups A, C, Y, and W was defined as: \n•For a subject with a pre -vaccination titer < 1:8, the post- vaccination titer had to be ≥ 1:16\n•For a subject with a pre -vaccination titer ≥ 1:8, the post- vaccination titer had to be ≥ 4-fold greater than \n       the pre -vaccination titerMET42 primary endpoint 1Percentage of subjects with vaccine seroresponse MET42: Post booster, MenACYW -TT seroresponse  rates were comparable to those \nfor MenACWY -CRM for serogroups A, Y, W and higher for serogroup C\n79.497 96.4 97.6\n77.688.292.396.4\n0255075100\nA C Y WParticipants achieving \nseroresponse  (%, 95% CI)\nGroup 1a: MenACYW-TT (N=675) Group 2a: MenACWY-CRM (N=308)14\nPrimary objective 1 was met: The percentage of subjects who achieved vaccine seroresponse  rate post -dose 4 for meningococcal \nserogroups A, C, W, and Y in MenACYW -TT (Group 1a) are non -inferior  to the corresponding percentages in MenACWY -CRM (Group 2a), as the \nlower limit of the 2 -sided 95% confidence interval (CI) of the difference between MenACYW -TT (Group 1a) and MenACWY -CRM (Group 2a) were \nhigher than -10% for all 4 serogroups \nImmunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine When Administered Concomitantly With Routine Pediatric  Vaccines in Healthy Infants and Toddlers in the \nUS. ClinicalTrials.gov, Sanofi Pasteur, 15 Oct. 2024, https://clinicaltrials.gov/study/NCT03537508  \nN: number of subjects in per -protocol analysis set 2, for booster series.\n95% CI of the single proportion calculated from the exact binomial method. \nGroup 1a: MenACYW -TT and routine vaccines at 2, 4, 6, and 12 to 15 months of age\nGroup 2a: MenACWY -CRM at 2, 4, 6, and 12 months of age and routine vaccines at 2, 4, 6, 12, and 15 \nto 18 months of age\nPPAS, Per -Protocol Analysis SetMET42 primary endpoint 2Percentage of subjects with hSBA titer >= 1:8 ( seroprotection )MET42: Post 3 -dose infant series, MenACYW -TT seroprotection rates were higher \nthan those for MenACWY -CRM for all 4 serogroups\n77.999 98.3 98.6\n67.791.2 91.7 92.9\n0255075100\nA C Y WParticipants achieving \nseroprotection (%, 95% CI)\nGroup 1a: MenACYW-TT (N=928) Group 2a: MenACWY-CRM (N=460)15\nPrimary objective 2 was met: Non-inferiority of the percentage of subjects with hSBA titers  to meningococcal serogroups A, C, Y, \nand W ≥ 1:8 following administration of 3 doses of MenACYW -TT compared to 3 doses of MenACWY -CRM when given concomitantly with \npediatric routine vaccines  to infants and toddlers at 6 to 7 months of age was demonstrated as the lower limit of the 2 -sided 95% CI of the \ndifference in hSBA  seroprotection  rates (antibody titers ≥ 1:8) were > -10% for all 4 serogroups\nImmunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine When Administered Concomitantly With Routine Pediatric  Vaccines in Healthy Infants and Toddlers in the \nUS. ClinicalTrials.gov, Sanofi Pasteur, 15 Oct. 2024, https://clinicaltrials.gov/study/NCT03537508  \n10.6\n6.6461.3\n4.4543.5\n9.9757.9\n9.0267.156.9678\n90.9296\n186387\n175\n1101001000Geometric means of hSBA \ntiters\nLog scaleD0 D30MET42: Geometric mean of hSBA antibody titers pre-  and post - 4th dose \nSummary of secondary immunogenicity results\nD, day; \n95% CI calculated using calculation for normal distribution on log10( titer) following by antilog transformation\nGroup 1a: MenACYW -TT and routine vaccines at 2, 4, 6, and 12 to 15 months of age\nGroup 2a: MenACWY -CRM at 2, 4, 6, and 12 months of age and routine vaccines at 2, 4, 6, 12, and 15 to 18 months of ageSecondary objective 2: Geometric mean of hSBA  antibody titers against meningococcal serogroups A, C, Y and W after 4th dose of \nMenACYW -TT were comparable or generally higher for all serogroups for Group 1a vs Group 2a\nSummary of geometric means of hSBA titers at D0 before the 4th dose and D30 after the 4th dose - Per-Protocol Analysis Set 3\nSerogroup A C Y WGroup 1a Group 1a Group 1a Group 1a Group 2a Group 2a Group 2a Group 2a16\nSecondary objective 1 was met: Non-inferiority of immune responses of the routine pediatric vaccines administered concomitantly with \nMenACYW -TT as compared with MenACWY -CRM in infants and toddlers 6 weeks old to 18 months of age was demonstrated\nAb, antibody; ELISA, enzyme -linked immunosorbent assay; GMC, geometric mean concentrations; PRP, anti polyribosyl -ribitol  phosphate\n*Pertussis antigen: PT, FHA, PRN, and FIM; †Polioviruses: type 1, type 2, type 3; ‡Pneumococcal serotypes: 1, 3, 4, 5, 6A, 6B , 7F, 9V, 14, 18C, 19A, 19F, and 23F1st Year,\n30 days after the\n6-month \nvaccinationHepatitis B % ≥10 mIU/mL 10% Yes\nPRP % ≥0.15 µg/mL 5% Yes\nPRP % ≥ 1.0 µg/mL 10% Yes\nPolio† % ≥1:8 5% Yes\nRotavirus % ≥ 3 -fold rise 10% Yes\nRotavirus GMC (G1/G2 ratio) 1.5 Yes\nPertussis* GMC (G1/G2 ratio) 1.5 Yes\nPneumococcal‡ GMC (G1/G2 ratio) 2 YesEvaluation \nTimeAntigen EndpointNon-\ninferiority \nmarginNon-\ninferiority?\n2nd Year,\n30 days after the 12-month \nvaccinationMeasles % ≥ 255 mIU/mL 10% Yes\nMumps% ≥ 10 mumps Ab \nunits/mL10% Yes\nRubella % ≥ 10 IU/mL 10% Yes\nVaricella % ≥ 5 gpELISA units/mL 10% Yes\nPneumococcal‡ GMC (G1a/G2a ratio) 2 Yes\n2nd Year, \n30 days after the\n15-month \nvaccinationPRP % ≥1.0µg/mL 10% Yes\nPolio† % ≥1:8 5% Yes\nPertussis* Response rate 10% YesMET42: Results on concomitant administration of pediatric vaccines17\nImmunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine When Administered Concomitantly With Routine Pediatric  Vaccines in Healthy Infants and Toddlers in the \nUS. ClinicalTrials.gov, Sanofi Pasteur, 15 Oct. 2024, https://clinicaltrials.gov/study/NCT03537508  \nMenACYW -TT was non -inferior  to MenACWY -CRM, based on hSBA  vaccine seroresponse  after the 4th dose, when the vaccines \nwere given at 2, 4, 6, and 12 months of age, along with routine pediatric vaccines\nMenACYW -TT was non-inferior  to MenACWY -CRM, based on seroprotection  after the 3rd dose, when the vaccines were given at 2, \n4, 6, and 12 months of age along with routine pediatric vaccinesPrimary immunogenicity objectives were met\nNon-inferiority  of immune responses to routine pediatric vaccines administered concomitantly with MenACYW -TT as compared with \nMenACWY -CRM in infants and toddlers 6 weeks old to 18 months of age was demonstrated\nGeometric mean of hSBA  titers against meningococcal serogroups A, C, Y and W after 3rd dose of MenACYW- TT were comparable or \nhigher for all serogroups in  the MenACYW -TT group vs MenACWY -CRM group\nThere were no new safety concerns identified\nThe safety profile and tolerance of MenACYW -TT was comparable to MenACWY -CRM \nSafety data from 3211 subjects who received 4 doses of MenACYW -TT (MET41 and MET42) are shown on later slidesSecondary immunogenicity objectives were met\nSafetyMET42: Summary of results18\nImmunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine When Administered Concomitantly With Routine Pediatric  Vaccines in Healthy Infants and Toddlers in the \nUS. ClinicalTrials.gov, Sanofi Pasteur, 15 Oct. 2024, https://clinicaltrials.gov/study/NCT03537508  \nMET41\nSafety of a Quadrivalent \nMeningococcal Conjugate \nVaccine ( MenACYW -TT) \nAdministered Concomitantly \nwith Routine Pediatric Vaccines \nin Healthy Infants and Toddlers\n\nShort Study Title Immune Non -inferiority, Safety and Co -administration \nstudy in infants  & toddlers\nStudy PopulationAge ≥ 42 to ≤ 89 days\nNumber of \nparticipants2797\nMeningococcal -vaccine naïve \nStudy DesignGroup 1: MenACYW -TT + Routine pediatric vaccines\nGroup 2: MenACWY -CRM  + Routine pediatric vaccines\nVaccination ScheduleSingle dose of MenACYW -TT or MenACWY -CRM (2, 4, \n6, and 12 months )\nSafety follow upImmediate \nUnsolicited \nSystemic \nAEsWithin 30 minutes after each vaccination\nSolicited \nAEsDay 0 toDay 7 after each vaccination\nUnsolicited \nAEsDay 0 untilthenextstudy visit\nSAEs (AESIs \nand MAAEs)Visit 1 (day of first vaccination) until the end of the 6 -\nmonth follow -up period after the last vaccination.MET41: Phase III study of MenACYW -TT conjugate vaccine \nadministered to healthy infants and toddlers20\nSafety of a Quadrivalent Meningococcal Conjugate Vaccine Administered Concomitantly With Routine Pediatric  Vaccines in Healthy Infants and Toddlers (MET41). ClinicalTrials.gov , Sanofi \nPasteur, 14 Dec. 2023, https://clinicaltrials.gov/study/NCT03673462  Baseline CharacteristicsGroup  1\n(N=2099)Group  2\n(N=362)\nSex: n (%)\nMale 1101 (52.5) 362 (51.9)\nFemale 998 (47.5) 336 (48.1)\nSex ratio: Male/Female 1.10 1.08\nAge: (Days)\nMean  (SD) 64.7 (6.63) 64.9 (6.77)\nMin ; Max 42.0 ; 89.0 42.0 ; 89.0\nMedian 63.0 63.0\nRacial  origin:  n (%)\nAmerican Indian or Alaska  \nNative 8 (0.4) 0 \nAsian 28 (1.3) 12 (1.7)\nBlack or African American 210 (10.0) 67 (9.6)\nNative  Hawaiian  or Other  Pacific  \nIslander10 (0.5) 5 (0.7)\nWhite 1719 (81.9) 580 (83.1)\nMixed  Origin 102 (4.9) 31 (4.4)\nUnknown 12 (0.6) 0\nEthnicity:  n (%)\nHispanic or Latino 566 (27) 197 (28.2)\nNot Hispanic or Latino 1526 (72.7) 499 (71.5)\nUnknown 0 0\nNot reported 7 (0.3) 9 (0.3)\nSummary of SAEs, AESIs and unsolicited AEs after any vaccine injections\nAESIs, adverse events of special interest; *Brighton Collaboration is a Global Standard for Case Definitions (and Guidelines) for Adverse Events Following Immunization (AEFI) and adverse events of special interest \n(AESI). 12 discontinuations occurred due to AEs throughout the study129/2797 (4.6%) subjects reported serious adverse events (SAEs) . None of these SAEs were assessed to be related to the study vaccines.\n20/2797 (0.7%) subjects reported 24 AESIs ( febrile or non -febrile seizures ), none related to the study vaccines.\n•19/2080 (0.9%) of AESIs occurred in the MenACYW -TT group.\n•1/697 (0.1%) of AESIs occurred in the MenACWY -CRM group. •The most common non -serious unsolicited adverse events (AEs) were in the \"Infections and Infestations\", with respiratory and \ngastrointestinal infections being the most frequently reported\n•108/2080 (5.2%) of subjects in the MenACYW -TT group reported SAEs.\n•21/697 (3%) of subjects in the MenACWY -CRM group reported SAEs. MET41: Summary of results\n•Confounding factors were identified in 21/24 (87.5%) of the AESI cases.\n•22/24 (92%) of AESI cases did not meet the Brighton Collaboration* case definition criteria for febrile and non -febrile \nseizures. \n•7 subjects (all in MenACYW -TT) discontinued due to SAEs, including 3 deaths (non- accidental injury to the head, sudden \nunexplained death in infancy, found unresponsive)\n•None were considered related to the study vaccine or procedure by the investigator and sponsor.21\nSafety of a Quadrivalent Meningococcal Conjugate Vaccine Administered Concomitantly With Routine Pediatric  Vaccines in Healthy Infants and Toddlers (MET41). ClinicalTrials.gov, Sanofi \nPasteur, 14 Dec. 2023, https://clinicaltrials.gov/study/NCT03673462  \nMET41 and MET42 pooled safety analysis22\n0.52.1 1.25.2\n0.3 1.1 0.93.7\n0102030405060708090100\nWithin 7 days after any vaccine\ninjections (SafAS for full 4-dose)Within 30 days after any vaccine\ninjections (SafAS for full 4-dose)During 6-month follow-up period\n(SafAS for full 4-dose)During the study\n(SafAS for full 4-dose)MenACYW-TT + routine pediatric vaccines\n(N=3211)MenACWY-CRM + routine pediatric vaccines(N=1327)\n1. Safety of a Quadrivalent Meningococcal Conjugate Vaccine Administered Concomitantly With Routine Pediatric Vaccines in Health y Infants and Toddlers (MET41). ClinicalTrials.gov, \nSanofi Pasteur, 14 Dec. 2023, https://clinicaltrials.gov/study/NCT03673462   2. Immunogenicity and Safety of a Quadrivalent Meningococcal Conjugate Vaccine When Administered \nConcomitantly With Routine Pediatric Vaccines in Healthy Infants and Toddlers in the US. ClinicalTrials.gov, Sanofi Pasteur, 15 Oct. 2024, https://clinicaltrials.gov/study/NCT03537508  Participants experiencing at least one SAEPercentage of participants\nMET61\nPhase III, modified double -blind, \nrandomized, parallel group, \nactive -controlled, multicenter  \nstudy of Quadrivalent \nMeningococcal Conjugate \nVaccine ( MenACYW -TT) in \ninfants & toddlers from 6 \nthrough 23 months of age in the \nUnited States\nShort Study Title Immune Non -inferiority, Safety and Co -administration study in infants  & \ntoddlers\nStudy PopulationAge Infants 6 to 7 months; Toddlers 17 to 19 months \nNumber of \nparticipants950\nStudy DesignGroup 1 : MenACYW -TT \nconjugate vaccine + routine pediatric vaccines at 6 to 7months of age and 12 to \n13months of age\nGroup 2 : MenACWY -CRM + \nroutine pediatric vaccines at 6 to 7months of age and 12 to \n13months of ageGroup 3 : MenACYW -TT conjugate \nvaccine at 17 to 19 months of age and 20 to 23 months of age\nGroup 4 : MenACWY -D at 17 to 19 \nmonths of age and 20 to 23 months of age\nSafety follow upImmediate Unsolicited Systemic AEs: 30 minutes post- vaccination. \nSolicited AEs: D0 to D7 post- vaccination\nUnsolicited AEs: D0 until the next visit\nSAEs (AESIs and MAAEs): Visit 1 to 6 -month follow -upMET61: Phase III Study of immunogenicity and safety of a quadrivalent \nmeningococcal conjugate vaccine administered concomitantly with routine \npediatric vaccines in healthy infants and toddlers\nBaseline \nCharacteristicsGroup 1+2Group\n 3+4\nCharacteristic \n(950)n=750 n=200\nSex, n (%)Male\nFemale398 (53.1)  100 (50.0)\n352 (46.9) 100 (50.0)\nAge in years, \nmean (SD)6.01 (0.570) 17.9 (0.652)\nRace, n (%)WhiteAfrican -\nAmericanMixed Origin541 (72.1)\n138 (18.4)\n35 (4.5)166 (83.0)\n22 (11.0)\n9 (4.5)\nEthnicity, n \n(%)\nHispanic or \nLatino330 (44.0)66 (33.0)24\nImmunogenicity and Safety Study of a Quadrivalent Meningococcal Conjugate Vaccine Administered Concomitantly With Routine Pediatric  Vaccines in Healthy Infants and Toddlers. \nClinicalTrials.gov, Sanofi Pasteur, 25 June 2024, https://clinicaltrials.gov/study/NCT03691610  \nMET61\nSafety\n\nMET61: Solicited injection site reactions within 7 days after any dose  \nGroup 1 (G1): MenACYW -TT vaccine + routine pediatric vaccines at 6 to 7 months of age and 12 to 13 months of age\nGroup 2 (G2): MenACWY -CRM vaccine + routine pediatric vaccines at 6 to 7 months of age and 12 to 13 months of age\nGroup 3 (G3): MenACYW -TT vaccine at 17 to 19 months of age and 20 to 23 months of age\nGroup 4 (G4): MenaACWY -D vaccine at 17 to 19 months of age and 20 to 23 months of age26\nImmunogenicity and Safety Study of a Quadrivalent Meningococcal Conjugate Vaccine Administered Concomitantly With Routine Pediatric  Vaccines in Healthy Infants and Toddlers. \nClinicalTrials.gov, Sanofi Pasteur, 25 June 2024, https://clinicaltrials.gov/study/NCT03691610  Majority of injection site reactions were Grade 1 (erythema and swelling) and Grade 1 & 2 (tenderness)33.130.236.333\n029.9 27.831.9\n24\n02219.624.2\n1314\n11.711\n7\n00.81.20\n2\n00.3\n0.91.1\n12.5\n2.30\n1\n00\n0.6 0\n0\n00.30.30\n0\n0102030405060708090100\nG1 G2 G3 G4 G1 G2 G3 G4 G1 G2 G3 G4\nErythema SwellingInjection Site Reactions\nGrade 1\nGrade 2\nGrade 3\nTendernessPercentage of participants\nMET61: Solicited systemic reactions within 7 days after any dose  27\nImmunogenicity and Safety Study of a Quadrivalent Meningococcal Conjugate Vaccine Administered Concomitantly With Routine Pediatric  Vaccines in Healthy Infants and Toddlers. \nClinicalTrials.gov, Sanofi Pasteur, 25 June 2024, https://clinicaltrials.gov/study/NCT03691610  25.828.724.227\n026.4 26.9 26.422\n03231.3\n23.1 23\n015.719.623.1 23\n01110.36.71124.2 20.8\n20.919\n016.611.7 11\n9\n010.4 11.4\n7.74\n05.93.57.7 9\n04.9 5.56.766.75\n3.36\n2 1.81.1\n32.5 3.2\n0\n31.71.20 2\n0.9 1.2 1.11\n0102030405060708090100\nCrying abnormal Drowsiness Appetite lost FeverSystemic Reactions\nGrade 1\nGrade 2\nGrade 3\nIrritability Crying abnormal Drowsiness Appetite lost FeverG1 G2 G3 G4 G1 G2 G3 G4 G1 G2 G3 G4 G1 G2 G3 G4 G1 G2 G3 G4\nVomiting  occurred less frequently, with 11.8%, 10.8%, 7.7%, and 9% reported in groups 1, 2, 3, and 4, respectivelyPercentage of participants\nGroup 1 (G1): MenACYW -TT vaccine + routine pediatric vaccines at 6 to 7 months of age and 12 to 13 months of age\nGroup 2 (G2): MenACWY -CRM vaccine + routine pediatric vaccines at 6 to 7 months of age and 12 to 13 months of age\nGroup 3 (G3): MenACYW -TT vaccine at 17 to 19 months of age and 20 to 23 months of age\nGroup 4 (G4): MenaACWY -D vaccine at 17 to 19 months of age and 20 to 23 months of age\nSummary of safety events after any vaccine injections\nAESIs, adverse events of special interest MET61: Summary of results28\nImmunogenicity and Safety Study of a Quadrivalent Meningococcal Conjugate Vaccine Administered Concomitantly With Routine Pediatric  Vaccines in Healthy Infants and Toddlers. \nClinicalTrials.gov, Sanofi Pasteur, 25 June 2024, https://clinicaltrials.gov/study/NCT03691610  •A total of 6 participants (1.6%) in Group 1 (MenACYW -TT), 12 participants (3.3%) in Group 2 (MenACWY -CRM), 1 participant (1.0%) \nin Group 3 (MenACYW -TT), and 4 participants (3.9%) in Group 4 (MenACWY -D) reported SAEs during the study\n•One participant (1.0%) in Group 4 ( MenACWY -D) experienced an SAE (febrile convulsions) that was considered related to vaccination. \nThis was reported as an adverse event of special interest (AESI).\n•All other SAEs were evaluated as non -related to vaccination by Investigators and Sponsor•One participant in Group 2 ( MenACWY -CRM) experienced an immediate unsolicited AE (head injury)\n•There  was 1 SAE (acute myeloid leukemia not related to the study vaccines), leading to study discontinuation in Group 2 ( MenACWY -\nCRM)\n•One participant (0.3%) in Group 1 (MenACYW -TT), 2 participants (0.6%) in Group 2 (MenACWY -CRM), and 2 participants (1.9%) in \nGroup 4 (MenACWY -D) reported an AESI during the study.  None of these AESI were related to the study vaccines.\n•No deaths were reported during the study\nMET61\nImmunogenicity\n\nMET61: Post booster, MenACYW -TT seroresponse rates were high and \ncomparable to those for MenACWY -CRM for all 4 serogroups\n95% CI of the single proportion calculated from the exact binomial method. \nGroup 1: MenACYW -TT vaccine + routine pediatric  vaccines at 6 to 7 months of age and 12 to 13 \nmonths of age\nGroup 2: MenACWY -CRM + routine pediatric  vaccines at 6 to 7 months of age and 12 to 13 \nmonths of ageVaccine seroresponse* at day 30 after the booster dose (Group 1 vs Group 2) in Per -protocol Analysis Set \n*hSBA  vaccine seroresponse  for serogroups A, C, Y, and W was defined as: •For a subject with a pre -vaccination titer < 1:8, the post- vaccination titer had to be \n≥1:16\n•For a subject with a pre -vaccination titer ≥ 1:8, the post- vaccination titer had to be \n≥4-fold greater than the pre -vaccination titer89.499.3 98.6 99.3\n82.997.6 97.792.9\n0255075100\nA C Y WParticipants achieving \nseroresponse (%, 95% CI)\nGroup 1: MenACYW-TT (N=180) Group 2: MenACWY-CRM (N=163)MET 61 primary endpoint 130\nPrimary objective 1 was met: Post second vaccination at 12 to 13 months of age, non -inferiority of the group 1 vs. group 2 showed the lower \nlimit of the 95% confidence interval (CI) of the difference in hSBA  seroresponse  for meningococcal serogroups A, C, W, and Y was above - 10%\nImmunogenicity and Safety Study of a Quadrivalent Meningococcal Conjugate Vaccine Administered Concomitantly With Routine Pediatric  Vaccines in Healthy Infants and Toddlers. \nClinicalTrials.gov, Sanofi Pasteur, 25 June 2024, https://clinicaltrials.gov/study/NCT03691610  Percentage of subjects with vaccine seroresponse  \nSeroprotection : hSBA  antibody titers  ≥ 1:8\nN: number of subjects in per -protocol analysis set 2, for booster series.\n95% CI of the single proportion calculated from the exact binomial method. \nGroup 1: MenACYW - TT vaccine + routine pediatric  vaccines at 6 to 7 months of age and 12 to 13 months of age\nGroup 2: MenACWY -CRM + routine pediatric  vaccines at 6 to 7 months of age and 12 to 13 months of age\nPPAS, Per -Protocol Analysis SetPercentage of subjects with seroprotection\n95.3100 100 1009398.1 97.5 95.6\n0255075100\nA C Y WParticipants achieving \nseroprotection (%, 95% CI)\nGroup 1: MenACYW-TT (N=180) Group 2: MenACWY-CRM (N=163)MET 61 secondary endpoint 131\nImmunogenicity and Safety Study of a Quadrivalent Meningococcal Conjugate Vaccine Administered Concomitantly With Routine Pediatric  Vaccines in Healthy Infants and Toddlers. \nClinicalTrials.gov, Sanofi Pasteur, 25 June 2024, https://clinicaltrials.gov/study/NCT03691610  MET61: Post booster, MenACYW -TT seroprotection  rates were high and \ncomparable to those for MenACWY -CRM for all 4 serogroups\nSecondary objective was met: Post-second vaccination at 12 -13 months, group 1 demonstrated that at D30, the lower limit of the 95% \nconfidence interval (CI) for the difference in subjects achieving seroprotection  (hSBA  ≥1:8) for serogroups A, C, W, and Y was above - 10% \ncompared to group 2.\nMET61 : Geometric mean of hSBA  antibody titers pre- and post -2nd \nvaccination with MenACYW -TT and MenACWY -CRM\n \n32Summary of secondary immunogenicity results\nD, day; GMT, geometric mean titer ; hSBA , human serum bactericidal assay;  \n95% CI calculated using calculation for normal distribution on log10( titer) following by antilog transformation\nGroup 1: MenACYW -TT vaccine  + routine pediatric vaccines at 6 to 7 months of age and 12 to 13 months of age\nGroup 2: MEenACWY -CRM vaccine + routine pediatric vaccines at 6 to 7 months of age and 12 to 13 months of ageSecondary objective: At D0 (pre- dose 1), baseline hSBA  GMTs for serogroups A, C, Y, and W were comparable between groups, but at D30 \npost-dose 2 (12– 13 months), they were higher in Group 1 for all serogroups\nSummary of geometric means of hSBA  titers at pre-dose D1 and D30 after the 2nd vaccination at 12 -13 months dose -  Per-Protocol Analysis Set 2\nSerogroup A C Y W32Geometric  means of hSBA \ntiters\nLog scale\n4.73 4.64\n2.57 2.48 2.54 2.37 2.23 2.311841191473\n319423\n133442\n106\n110100100010000\nGroup 1 Group 2 Group 1 Group 2 Group 1 Group 2 Group 1 Group 2D1 D30\nMET61 : Geometric mean hSBA  titers pre - and post -2nd vaccination with \nMenACYW -TT and MenACWY -D\n33Summary of secondary immunogenicity results\nD, day; GMT, geometric mean titer ; hSBA , human serum bactericidal assay; \n95% CI calculated using calculation for normal distribution on log10( titer) following by antilog transformation\nGroup 3: MenACYW -TT vaccine at 17 to 19 months of age and 20 to 23 months of age\nGroup 4: MenACWY -D at 17 to 19 months of age and 20 to 23 months of ageSecondary objective: At D0 (pre- dose 1), hSBA  GMTs were comparable between groups, but at 30 days post -dose 2 (20– 23 months), they \nwere higher in Group 3 for all serogroups\nSummary of geometric means of hSBA  titers at pre-dose D1 and D30 after the 2nd vaccination at 20 -33 months dose -  Per-Protocol Analysis Set 2\nSerogroup A C Y W33Geometric means of hSBA \ntiters\nLog scale\n4.293.432.1 2.41 2.44 2.442.02 2.1245\n13.21727\n59.4284\n45.5202\n25\n110100100010000\nGroup 3 Group 4 Group 3 Group 4 Group 3 Group 4 Group 3 Group 4D1 D30\nGroup 3 Group 4 Group 3 Group 4 Group 3 Group 4 Group 3 Group 4\nSummary of immunogenicity findings\nSeroresponses  at day 30 following the first dose of MenACYW -TT vaccine co -administered with routine pediatric  vaccines were non-\ninferior  to those seen after administration of a primary dose of MenACWY -CRM with routine pediatric  vaccines MET61: Summary of results\n• The percentages of participants in both groups with ≥4 -fold rise in titers  pre- vs 30 days post -dose 2 were \ncomparable for all 4 serogroupsSix to 7 months following administration of a dose of MenACYW -TT vaccine to infants 6 -7 months of age , geometric mean \ntiters  (GMTs) were comparable  to those seen after administration of a dose of MenACWY -CRM for serogroup A and higher for \nserogroups C, W, and Y\nThirty days after dose 2 administered at 20 -23 months of age , the hSBA  GMTs were higher for all serogroups in \nparticipants administrated MenACYW -TT vaccine compared to those who received MenACWY -D\n• The percentages of participants with a ≥ 4-fold rise in hSBA  GMTs  for serogroups C, Y, and W were comparable \nbetween the 2 vaccine groups and higher for serogroup A after MenACYW -TT vaccine administration compared to \nMenACWY -D\nMenACYW -TT vaccine  is immunogenic and  demonstrates  an acceptable  safety  profile  \nwhen  administered  to infants  6 months  through 23 months  of age in a 2-dose  \nschedule .34\nImmunogenicity and Safety Study of a Quadrivalent Meningococcal Conjugate Vaccine Administered Concomitantly With Routine Pediatric  Vaccines in Healthy Infants and Toddlers. \nClinicalTrials.gov , Sanofi Pasteur, 25 June 2024, https://clinicaltrials.gov/study/NCT03691610  \nConclusion\nMenACYW -TT demonstrated robust immunogenicity & reassuring safety \nprofile in infants & toddlers starting vaccination as early as 6 weeks of \nage\n•The expanded indication for MenACYW -TT is a valuable public health option to facilitate \nimmunization across the lifespan from 6 weeks & above\n•Immunogenicity  results demonstrate non -inferior immune responses, administered with \nroutine pediatric vaccines, compared to currently licensed MenACWY  conjugate vaccines\n•No unexpected safety concerns were found in infants and toddlers (from 6 weeks to 23 \nmonths) compared to the safety profile in individuals ≥2 years and other licensed \nMenACWY  conjugate vaccines\n•No relevant safety profile differences were observed based on sex or race\n•The safety profile of 237 infants with a history of preterm birth (31-36 weeks \ngestational age)** was comparable to infants who had been born full -term, with no new \nsafety concerns or AEs leading to study discontinuation \n 36** all prematurely born infants were either enrolled in studies MET41 and MET42\nThank\nyou", "summary": "FOR USE ONLY BY SANOFI MEDICAL AFFAIRS FOR SCIENTIFIC EXCHANGE PURPOSES. DO NOT COPY OR DISTRIBUTEMAT-US-2204183 -R -NONDISTRIB -EXP 7/3/26 Meningococcal  (Groups A, C, Y,  andW) Conjugate  Vaccine ( MenQuadfi®) Extension of use to include  infants from 6 weeks of age  Agenda Public health  burden of invasive  meningococcal  diseaseRationale for clinical  developmentClinical data from  infant studiesSummary 2 Public health burden of meningococcal disease  •Meningococcal disease remains a major…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/05-Dawson-Mening-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 37}
{"title": "06 Schillie mening 508", "content": "Work Group Considerations Regarding \nMenQuadfi in Infants\nSarah Schillie, MD, MPH, MBA\nAdvisory Committee on Immunization Practices\nApril 16, 2025National Center for Immunization & Respiratory Diseases\n1\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position o f \nthe U. S. Centers for Disease Control and Prevention.\nStudies Reviewed\nThree Phase III studies in U.S. infants aged 6 weeks – 19 \nmonths\n– 4,321 infants enrolled in MenACWY -TT arm\n•2 studies:  3+1 schedule (ages 2, 4, 6, 12 or 12– 18 months)\n•1 study:  1+1 schedule (age ≥6 months)\n–Comparator vaccine:  1,717 infants received MenACWY -CRM or \nMenACWY -D\nVaccine co -administered with pediatric vaccines (6 arms)\n2 of 13\nSeroresponse:  Met42\n3 of 13\n\nSeroresponse:  Met61\n4 of 13\n4 of 11\nSolicited Local and Systemic Adverse Reactions:  Met42\nGroup 1= \nMenACWY -TT \n+ routine pediatric vaccines\nGroup 2 \n=MenACWY -\nCRM + routine pediatric vaccines\n5 of\n 13\n\nSolicited Local Adverse Reactions:  Met61\nGroup 1= MenACWY -TT + \nroutine pediatric vaccines \nat 6-7 months and 12 -13 \nmonths\nGroup 2 =MenACWY -CRM \n+ routine pediatric \nvaccines at 6 -7 months \nand 12 -13 months\nGroup 3 =MenACWY -TT at \n17-19 months and 20 -23 \nmonths\nGroup 4 =MenACWY -D at \n17-19 months and 20 -23 \nmonths\n6 of 13\nSolicited Systemic Adverse Reactions:  Met61\nGroup 1= MenACWY -TT + \nroutine pediatric vaccines \nat 6-7 months and 12 -13 \nmonths\nGroup 2 =MenACWY -CRM \n+ routine pediatric \nvaccines at 6 -7 months \nand 12 -13 months\nGroup 3 =MenACWY -TT at \n17-19 months and 20 -23 \nmonths\nGroup 4 =MenACWY -D at \n17-19 months and 20 -23 \nmonths\n7 of 13\nSAEs, AESIs, and Unsolicited AEs\nMet41:  Imbalance of febrile/non- febrile seizures\n–19 subjects in intervention group (n=2080, 0.9%) vs. 1 in \ncomparison group (n=697, 0.1%) with febrile or non -febrile \nseizures\n–All deemed not related to study vaccine by primary investigator and sponsor\nMet42:  1 febrile seizure who received study vaccine\n–Prior history of seizures/deemed related to study vaccine \nSAE, serious adverse event; AESI, adverse event of special interest; AE, adverse event8 of 13\nSAEs, AESIs, and Unsolicited AEs, cont.\n4 total deaths, all in intervention group and all deemed \nunrelated to study vaccine by primary investigator and sponsor\n–Met41:  \n•Non -accidental injury of the head (30 days after vaccination)\n•Sudden unexplained death in infancy (24 days after vaccination)\n•Found by parent unresponsive in bed (4 days after vaccination)\n–Met42:  \n•Cardiac arrest (6 days after vaccination)  \n–Met61:  \n•No deaths\nSAE, serious adverse event; AESI, adverse event of special interest; AE, adverse event9 of 13\nPooled Safety Analysis:  Met41 and Met42\n10 of 13\n\nSummary\nPost -dose 4 seroresponse  overall similar for MenQuadfi vs. comparator\n–Higher GMTs for Serogroup C among MenQuadfi  recipients (vs. comparator)  \nSafety\n–Solicited local and systemic reactions generally similar between \nstudy groups\n•Local reactions slightly greater for MenQuadfi  in Met61\n–Among MenQuadfi recipients in Met41 and Met42, greater \nproportion of:\n•Febrile/non -febrile seizures\n•Serious Adverse Events\n•Deaths 11 of 13\nSummary, cont.\nResults among healthy infants may not be representative of \nresults for infants recommended for vaccine based on risk factors\n–Similar studies typically limited to healthy infants \nHigh attrition rates \n–Attributed to out -of-window visits, missed blood draws, COVID -19 \npandemic\nBenefits of another vaccine option may outweigh risks\n12 of 13\n13Acknowledgements\nLucy McNamara\nAvnika Amin\nAlison Albert\nAmy Rubis\nLeAnne Fox\nNoele Nelson\nSusan Hariri\n2 of 1113 of 13", "summary": "Work Group Considerations Regarding  MenQuadfi in Infants Sarah Schillie, MD, MPH, MBA Advisory Committee on Immunization Practices April 16, 2025National Center for Immunization & Respiratory Diseases 1 The findings and conclusions in this report are those of the authors and do not necessarily represent the official position o f  the U. S. Centers for Disease Control and Prevention. Studies Reviewed Three Phase III studies in U.S. infants aged 6 weeks – 19  months – 4,321 infants enrolled in…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/06-Schillie-mening-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 13}
{"title": "01 Shaw Adult RSV 508", "content": "RSV Vaccination in Adults:\nIntroduction\nAlbert Shaw, MD, PhD\nChair, Adult RSV Work Group\nAdvisory Committee on Immunization Practices\nApril 16, 2025National Center for Immunization and Respiratory Diseases\n2Adult RSV Work Group Membership\nACIP Voting Members\nAlbert Shaw (Chair)\nHelen Chu\nMini Kamboj\nKeipp Talbot \nEx Officio Members\nNicholas Geagan (FDA)\nRachel Zhang (FDA) \nMichelle Juaneza (HRSA)\nUzo Chukwuma (IHS)\nSonnie Kim (NIH/NIAID)CDC Co -Leads\nAmadea Britton\nMichael Melgar\nDiya SurieConsultants\nRobert Atmar (Baylor College of Medicine)\nPeter Donofrio (Vanderbilt University)\nMarie Griffin (Vanderbilt University)\nCamille Kotton (Massachusetts General Hospital)\nCynthia Lucero (Veterans Health Administration)\nTracy Ruckwardt (NIH/NIAID)\nJonathan Temte  (University of Wisconsin)Liaisons\nBindy Crouch (AIM)\nApril Killikelly (NACI, PHAC)\nGretchen LaSalle (AAFP)\nRuth Lynfield (NFID) \nSteven Pergam (IDSA)\nKenneth Schmader (AGS)\nWinnie Siu (NACI, PHAC)\nElizabeth Skoy ( APhA )\nVidya Sundareshan (ACP)\nKatherine Williams (APTR) \n3CDC Contributors\nMelissa Coughlin\nFatima Dawood\nJarrett Gartin\nMonica Godfrey\nFiona Havers\nSuzanne Heitfield\nMichele Hlavsa\nJefferson Jones\nRuth Link -Gelles\nAmber Kautz\nAgustin  Lopez\nJosephine Mak\nMeredith McMorrow\nNoelle -Angelique MolinariDanielle Moulia\nIsmael Ortega -Sanchez\nLakshmi Panagiotakopoulos\nPragna Patel\nMonica Patton\nAmanda Payne\nMila Prill\nLauren Roper\nMelisa Shah\nNatalie Thornburg\nDennis Wang\nTrang WisardImmunization Safety Office\nTarayn Fairlie\nJulianne Gee\nAnne Hause\nSarah Meyer\nMichael McNeil\nPedro Moro\nChristine Olson\nDavid Shay\nJohn Su\nEvelyn Twentyman\nEric WeintraubImmunization Services Division\nCarla Black\nKayla Calhoun \nNicole Dowling\nJennifer Kriss\nAndrew Leidner\nJamison Pike\nInfluenza Division\nJill Ferdinands\nLisa GrohskopfNCIRD Office of the Director\nJessica MacNeil\nHannah Rosenblum\nMelinda WhartonCoronavirus and Other Respiratory Viruses Division \n4June 2024  ACIP Recommendations for RSV Vaccination \nin Older Adults:\nACIP recommends all adults aged ≥75 years and adults aged 60 –74 years \nwho are at increased risk of severe RSV disease receive a single dose of RSV \nvaccine.1,2\n1. Recommendation is for any Food and Drug Administration –approved RSV vaccine ( Arexvy  [GSK]; \nAbrysvo  [Pfizer]; or mResvia  [Moderna]). There is no product preference. \n2. Eligible adults are currently recommended to receive a single dose of RSV vaccine; adults who have \nalready received RSV vaccination should not receive another dose.\n5Chronic medical conditions and other risk factors associated \nwith increased risk of severe RSV disease \nNeurological or neuromuscular conditions \ncausing impaired airway clearance or \nrespiratory muscle weaknessChronic cardiovascular \ndisease\nModerate or severe \nimmunocompromise Diabetes mellitus  \ncomplicated by chronic kidney disease, \nneuropathy, retinopathy or other end -\norgan damage or requiring treatment \nwith insulin or sodium -glucose \ncotransporter -2 (SGLT2) inhibitorSevere obesity \n(body mass index \n≥40 kg/m2)Chronic lung \nor respiratory \ndisease\nEnd stage renal \ndisease/dialysis \ndependenceChronic liver \ndiseaseChronic hematologic \nconditions\nResidence in a \nnursing homeOther chronic medical conditions or risk factors that a \nprovider determines would increase risk of severe disease \ndue to viral respiratory infection (e.g., frailty) \nBritton A, Roper LE, Kotton CN, et al. Use of Respiratory Syncytial Virus Vaccines in Adults Aged ≥60 Years: Updated Recommen dations of the Advisory Committee on Immunization Practices — United States, 2024. MMWR Morb  Mortal Wkly  Rep 2024;73:696 -702. \nDOI: http://dx.doi.org/10.15585/mmwr.mm7332e1 .\n6•Protein subunit (based on RSV F protein in prefusion conformation)\n-GSK Arexvy1: monovalent RSV -A, AS01E adjuvant\n-Pfizer Abrysvo2: bivalent RSV -A/RSV -B, no adjuvant\n•Messenger RNA (mRNA, encoding RSV F protein in prefusion conformation)\n-Moderna mResvia3: monovalent RSV -A, no adjuvantCurrent FDA -approved RSV vaccines\n1. https://www.fda.gov/media/167805/download\n2. https://www.fda.gov/media/168889/download\n3. https://www.fda.gov/media/179005/download\n7•Protein subunit\n-GSK Arexvy1: monovalent RSV -A, AS01E adjuvant\n-Pfizer Abrysvo2: bivalent RSV -A/RSV -B, no adjuvant\n•mRNA\n-Moderna mResvia3: monovalent RSV -A, no adjuvantCurrent FDA -approved RSV vaccines\nApproved for prevention of \nlower respiratory tract \ndisease (LRTD) caused by RSV \nin adults aged ≥60 years\n1. https://www.fda.gov/media/167805/download\n2. https://www.fda.gov/media/168889/download\n3. https://www.fda.gov/media/179005/download\n8•Protein subunit\n-GSK Arexvy1: monovalent RSV -A, AS01E adjuvant\n-Pfizer Abrysvo2: bivalent RSV -A/RSV -B, no adjuvant\n•mRNA\n-Moderna mResvia3: monovalent RSV -A, no adjuvantCurrent FDA -approved RSV vaccines\nApproved for prevention of \nLRTD caused by RSV in adults \naged 50 –59 years who are at \nincreased risk for LRTD \ncaused by RSV*\n1. https://www.fda.gov/media/167805/download\n2. https://www.fda.gov/media/168889/download\n3. https://www.fda.gov/media/179005/download*There is no current ACIP recommendation for RSV \nvaccination in adults aged <60 years, except  for the maternal \nvaccination recommendation:\nhttps://www.cdc.gov/mmwr/volumes/72/wr/mm7241e1.htm  \n9•Protein subunit\n-GSK Arexvy1: monovalent RSV -A, AS01E adjuvant\n-Pfizer Abrysvo2: bivalent RSV -A/RSV -B, no adjuvant\n•mRNA\n-Moderna mResvia3: monovalent RSV -A, no adjuvantCurrent FDA -approved RSV vaccines\nApproved for prevention of \nLRTD caused by RSV in adults \naged 18 –59 years who are at \nincreased risk of LRTD \ncaused by RSV*\n1. https://www.fda.gov/media/167805/download\n2. https://www.fda.gov/media/168889/download\n3. https://www.fda.gov/media/179005/download*There is no current ACIP recommendation for RSV \nvaccination in adults aged <60 years, except  for the maternal \nvaccination recommendation:\nhttps://www.cdc.gov/mmwr/volumes/72/wr/mm7241e1.htm  \n10•Protein subunit\n-GSK Arexvy1: monovalent RSV -A, AS01E adjuvant\n-Pfizer Abrysvo2: bivalent RSV -A/RSV -B, no adjuvant\n•mRNA\n-Moderna mResvia3: monovalent RSV -A, no adjuvantCurrent FDA -approved RSV vaccines\nAlso approved and \nrecommended for active \nimmunization in pregnancy* \nat 32 –36 weeks gestational \nage for the prevention of \nLRTD and severe LRTD caused \nby RSV in infants from birth \nthrough 6 months of age.\n*There is no current ACIP recommendation for RSV \nvaccination in adults aged <60 years, except  for the maternal \nvaccination recommendation:\nhttps://www.cdc.gov/mmwr/volumes/72/wr/mm7241e1.htm  1. https://www.fda.gov/media/167805/download\n2. https://www.fda.gov/media/168889/download\n3. https://www.fda.gov/media/179005/download\n11•Protein subunit\n-GSK Arexvy1: monovalent RSV -A, AS01E adjuvant\n-Pfizer Abrysvo2: bivalent RSV -A/RSV -B, no adjuvant\n•mRNA\n-Moderna mResvia3: monovalent RSV -A, no adjuvantCurrent FDA -approved RSV vaccines\nPDUFA: Prescription Drug User Fee Act\n1. https://www.fda.gov/media/167805/download\n2. https://www.fda.gov/media/168889/download\n3. https://www.fda.gov/media/179005/download\n4. https://investors.modernatx.com/news/news -details/2025/Moderna -Reports -Fourth -Quarter -and-Fiscal -Year -2024 -Financial -Results -and-Provides -Business -\nUpdates/default.aspx  Moderna has submitted \nan application for \nlicensure for adults aged \n18–59 years who are at \nincreased risk of LRTD \ncaused by RSV. PDUFA \ndate June 12th, 2025.4\n12•Adult RSV Work Group will propose a policy recommendation for age expansion of \nthe use of RSV vaccines to include adults aged 50 -59 years at increased risk of severe \nRSV disease. \n•Immunobridging  and safety data in adults aged 50 -59 years at increased risk of \nsevere RSV disease were previously presented to ACIP by GSK and Pfizer; today \nModerna will present immunobridging  and safety data in adults aged 18 -59 years at \nincreased risk.\n•ACIP will also see presentations from manufacturers on immunogenicity and safety \nof re -vaccination and economic analyses of RSV vaccination in adults aged 50 -59 \nyears at increased risk.\n•Then we will share the complete Evidence to Recommendation framework and \npropose a policy recommendation for an ACIP vote.Today’s meeting\n13\nAcknowledging there is also one FDA -approved vaccine for RSV \nprevention in adults aged <50 years, the Work Group continues to \nevaluate recommendations for RSV vaccination in this age group\n14•The Work Group recognizes that certain adults aged <50 years may \nbenefit from RSV vaccination\n•However, the Work Group has indicated there are likely important \ndifferences in considering a recommendation for adults aged <50 years \ncompared to adults aged ≥50 years, including:\n-Absolute risk of RSV -associated disease and which medical conditions increase risk the most\n-Risk-benefit balance \n-Cost -effectiveness \n-Importance of ability to restore protection with revaccination \n•As of today’s meeting, information on the absolute risk of RSV -\nassociated disease among adults with risk conditions is still being \nanalyzed and estimates of risk -benefit balance and cost -effectiveness of \nvaccination in younger adults are not yet available. Policy for the use of RSV vaccines in adults aged <50 \nyears will be revisited at the June 2025 meeting. \n15•The Work Group is also reviewing or anticipates reviewing the following data \ndeemed critical for a recommendation in adults aged <50 years:\n-The projected balance of public health benefits and risks considering uncertainty in vaccine -\nassociated Guillain -Barré syndrome risk in a younger population\n-Evidence of RSV vaccine immunogenicity or effectiveness in adults with the most severely \nimmunocompromising conditions\n-The duration of protection over time in adults aged ≥60 years who were vaccinated in 2023\n-Available data on immunogenicity of revaccination with different vaccine platforms and \nrevaccination intervals\n•The Work Group has indicated it needs to review these data and needs additional \ntime to consider the best policy option in adults aged <50 years.\n•The Work Group welcomes ACIP’s thoughts about adults aged <50 years during \ndiscussion at the end of today’s session. Policy for the use of RSV vaccines in adults aged <50 \nyears will be revisited at the June 2025 meeting. \n16Agenda: Wednesday April 16, 2025\n•Manufacturer Presentation: mRNA -1345 (Moderna) \nImmunogenicity in Adults Aged 18 -59 Years at Increased Risk; 24 -\nMonth Re -Vaccination\n•Manufacturer Presentation: Arexvy  (GSK) 36 -Month Re -\nVaccination  \n•Economic Analysis of Adult RSV Vaccination, including benefits \nand risk discussion\n•Comparison of Economic Analyses of Adult RSV Vaccination\n \n•Evidence to Recommendations\n•Clinical Considerations \n \n•ACIP discussion and vote •Dr. Frances Priddy (Moderna)\n•Dr. Susan Gerber (GSK)\n•Dr. Ismael Ortega -Sanchez (CDC) on behalf of Dr. \nDavid Hutton (University of Michigan)\n•Dr. Ismael Ortega -Sanchez (CDC)\n•Dr. Michael Melgar, Dr. Diya Surie (CDC)\n•Dr. Diya Surie (CDC)\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position \nof the Centers for Disease Control and Prevention.", "summary": "RSV Vaccination in Adults: Introduction Albert Shaw, MD, PhD Chair, Adult RSV Work Group Advisory Committee on Immunization Practices April 16, 2025National Center for Immunization and Respiratory Diseases 2Adult RSV Work Group Membership ACIP Voting Members Albert Shaw (Chair) Helen Chu Mini Kamboj Keipp Talbot  Ex Officio Members Nicholas Geagan (FDA) Rachel Zhang (FDA)  Michelle Juaneza (HRSA) Uzo Chukwuma (IHS) Sonnie Kim (NIH/NIAID)CDC Co -Leads Amadea Britton Michael Melgar Diya…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/01-Shaw-Adult-RSV-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 17}
{"title": "02 Priddy Adult RSV 508", "content": "1\n© 2025  Moderna,  inc. All rights  reserved.RSV Vaccine  (mRNA -1345)  Update:\n-Safety  & Immunogenicity  in 18-59 Year  Olds \nat increased  Risk for RSV Disease *\n-Revaccination  of Adults  at 12 or 24 Months *\nACIP\nFrances  Priddy,  MD MPH \nApril  16, 2025\n* mRESVIA  has not been  authorized  for these  indications\n2\nRSV Vaccine  (mRNA -1345)  Clinical  Development\nNCT05127434,  NCT05330975,  NCT06060457,  NCT06067230\nEfficacy,  Immunogenicity,  Safety,  and Correlate  of Protection\nAdults  ≥60 years\nStudy  301\nAdults  ≥50 years\nStudy  302 - Part A and B\nConcomitant  Administration \nwith Standard  Dose  Influenza  or \nCOVID -19\nAdults  ≥65 years\nStudy  304\nConcomitant  Administration \nwith High  Dose  Influenza\nAdults  18-59 years\nStudy  303 – Part A\nSafety  and Immunogenicity  in \nAdults  at Increased  Risk\nAdults  ≥50 years\nStudy  302 – Part CAdults  ≥60 years\nStudy  301 – Part BAdults  with SOT ≥18 years\nStudy  303 – Part B\n12 Month  Revaccination\n 24 Month  Revaccination\nSafety  and Immunogenicity  in \nImmunocompromised\n© 2025  Moderna,  inc. All rights  reserved.\n3\nAdult  RSV hospitalizations\n•37% in 18-64-year -olds\n•24% in 50-64-year -olds\n•22% required  ICU \nadmission\n•3% in-hospital mortalityComorbidityIncidence  rate ratio  for those  with versus  those \nwithout  comorbidity  among  adults  18-64 years\n0 40\nAsthma2.0 – 3.6\nCAD0.9 – 7.0\nDiabetes3.4 – 11.4\nCOPD3.2 – 6.4\nCHF*13.3 – 33.2US Hospitalization  Rates  for RSV in 18-64 Year  Olds  with \nUnderlying  Conditions\nCAD  - coronary  artery  disease;  CHF - congestive  heart  failure;  COPD  - chronic  obstructive  pulmonary  disease;  RSV - respiratory  syncytial  virus\n*CHF  age 20-59 years\nBranche  AR, et al. Clin Infect  Dis. 2022.\nRSV-NET Analysis  –Adults  Hospitalized \nwith Laboratory  Confirmed  RSV\n2016 -2023  (N=16,575)Estimated  incidence  of RSV-associated  Hospitalization \nin 2 Regions  of New  York  State,  US, 2017 -2020  (N=1099)\nHavers  FP, et al. JAMA  Netw  Open . 2024.\n© 2025  Moderna,  inc. All rights  reserved.\n4\n© 2025  Moderna,  inc. All rights  reserved.mRNA -1345  in Adults,18 -59 Years, \nat Increased  Risk of RSV Disease\nStudy  303, Part A\nISIRV  2025\n5Study  Design  – Randomized  Double -Blind  Study  in\n18-59-Year -Old Adults  at Increased  Risk of RSV Disease\nStudy  303, Part A\nCoronary  Artery  Disease  (CAD) \nand/or\nCongestive  Heart  Failure  (CHF)mRNA -1345  Dose\nCOPD,  Persistent  Asthma , Pulmonary \nFibrosis,  and/or  Other  Chronic \nRespiratory  DiseasesUnderlying  Disease  Category\n50 µg\nN ~ 150\n50 µg\nN ~ 150\n50 µg\nN ~ 200Diabetes  Mellitus  1 or 2•Day 29 immunogenicity \ncompared  between  this \npopulation  and adults\n≥60 years  in pivotal\nefficacy  trial\n•Participants  followed  for \n24 months\nUnited  States\n Canada\n United  Kingdom\n© 2025  Moderna,  inc. All rights  reserved.\n6\nComparison  of seroresponse  rates  (SRR)  of 50 µg high-risk 18-59 years  olds vs\n50 µg ≥ 60-year -olds in pivotal  efficacy  study\n•Criteria  for Noninferiority:  95% CI of SRR difference  LB > -10%\nSecondary  ObjectiveKey Study  Objectives\nStudy  303, Part A\nPrimary  Objectives\n1.Safety  and tolerability  of the vaccine  in high-risk 18-59-year -olds\n2.Compare  RSV-A and RSV-B GMTs  at Day 29 after  a single  dose  of 50 µg in \nhigh-risk adults,  18-59 years,  versus  adults  ≥60 years  in the pivotal  phase  2/3 \nefficacy  trial\n•Criteria  for Noninferiority:  95% CI of GMR  LB > 0.667\n© 2025  Moderna,  inc. All rights  reserved.LB – lower  bound,  CI – confidence  interval;  GMR – geometric  mean  ratio;  SCR – seroconversion  rate;  SRR – seroresponse  rate\n7\n(stage  0,1,2,3,4)\n© 2025  Moderna,  inc. All rights  reserved.Underlying  Medical  Conditions  of Study  Participants\nPhysician -documentation  required  for all underlying  medical  conditions\n•CAD\n•CHF*\n•Chronic  respiratory  disease\n− COPD*\n− Persistent  asthma  – requiring  ≥1 maintenance  medication\n− Pulmonary  fibrosis\n− Other  chronic lung  disease\n•Stable  type  1 or type  2 diabetes  mellitus\n− Controlled  with ≥1 medication  started  90 days  prior  to Day 1\nCAD,  coronary  artery  disease;  CHF,  congestive  heart  failure;  COPD,  chronic  obstructive  pulmonary  disease;  RSV, respiratory  syncytial  virus.\n*Severity  of CHF and COPD  assessed  at baseline  using  NYHA  Functional  Classification  for CHF (stage  I, II, III, IV), or modified  MRC  Dyspnea  Scale  for COPD\n8\nSept  18, 2024  data  cutoff\n© 2025  Moderna,  inc. All rights  reserved.Demographics  of Study  Participants\nStudy  303, Part A, Safety  Set\nmRNA -1345  (50 µg)\nMedical  History  Category18-59 years\nN = 50250-59 years\nN = 306\nMedian  Age,  years  (range) 53 (19-59) 56 (50-59)\nFemale,  n (%) 269 (54%) 158 (52%)\nRace/Ethnicity,  n (%)\nWhite 401 (80%) 238 (78%)\nBlack  or African  American 85 (17%) 64 (21%)\nAsian 4 (1%) 2 (1%)\nHispanic  / Latino  Ethnicity 140 (28%) 88 (29%)\n•Study  population  was racially/ethnically  diverse\n© 2025  Moderna,  inc. All rights  reserved.\n9\nSafety  – mRNA -1345  in Adults, \n18-59 Years,  at Increased  Risk of \nRSV Disease\nStudy  303, Part A\n10\nLocal  Reactions  - Vaccine  Generally  Well Tolerated  in Adults, \n18-59 Years,  at Increased  Risk for RSV Disease\nSolicited  Local  Reactions  within  7 Days  of Injection  compared  to Older  Adults  ≥60 Years\nSolicited Safety  Set – Studies  303 Part A (N = 502) & 301 (N = 18,160)\n74%\n56%\n2% 2%5% 4%17%15%\n0%20%40%60%80%100% Injection  Site Injection  Site Injection  Site Axillary  Swelling\nPain Erythema  Swelling  or Tenderness\nGrade  3 or 4\nGrade  2\nGrade  1\nStudy  303\nSept  18, 2024  data  cutoff  - Study  303\n© 2025  Moderna,  inc. All rights  reserved.Study  301 Study  303 Study  301 Study  303 Study  301 Study  303 Study  301\n•Injection  site pain  was more  common  among  high -risk adults,  18-59 years,  than  adults  ≥ 60 years\n•Rates  of other  local  reactions  generally  similar  across  age groups\n•Mostly  grade 1 -2, onset  days  1-2; median  duration  of 2 days;  1 grade  4 pain\n11Systemic  Reactions  - Vaccine  Generally  Well Tolerated  in \nAdults,  18-59 Years,  at Increased  Risk for RSV Disease\nSolicited  Systemic  Reactions  within  7 Days  of Injection  compared  to Older  Adults  ≥60 Years\nSolicited Safety  Set – Studies  303 Part  A (N = 502) & 301 (N = 18,160)\n4% 3%33%\n27%37%\n31%29%26%23% 22%\n11%7%20%\n12%20%40%60%80%100%Nausea/ \nVomitingChills\n0%\nStudy  303 Study  301  Study  303 Study  301 Study  303 Study  301  Study  303 Study  301 Study  303 Study  301  Study  303 Study  301  Study  303 Study  301\n•Rates  of systemic  reactions  generally  similar  or slightly  higher  among  18-59-year -olds vs adults  ≥60 years  old\n•Mostly  grade  1-2, onset  days  1-2; median  duration  of 2 days;  no grade  4 reactions\nFever  Headache  Fatigue  Myalgia  Arthralgia\nGrade  3\nGrade  2\nGrade  1\nSept  18, 2024  data  cutoff  – Study  303\n© 2025  Moderna,  inc. All rights  reserved.\n12\n•No anaphylaxis,  thrombocytopenia,  Guillain -Barré  syndrome,  acute  disseminated \nencephalomyelitis  (ADEM),  or acute  myocarditis  or acute  pericarditisUnsolicited  Adverse  Events  Within  28 Days  After  mRNA -1345\nRegardless  of Relationship  to Study  Vaccination\nStudy  303, Part A - Adults  at Increased  Risk of RSV – Safety  Set\nSept  18, 2024  data  cutoff\n30 µg, N=497;  50 µg, N=502\n* 30 µg group,  50-59 year  olds,  unrelated  to study  injection  by investigator:  one case  of pneumonia,  one case  of asthma  exacerbation,  both  RSV RT-PCR negative\n© 2025  Moderna,  inc. All rights  reserved.mRNA -1345\n18-59 years\nTotal  = 999mRNA -1345\n50-59 years\nN = 607\nAll, n (%) 226 (22.6%) 131 (21.6%)\nNon-Serious 224 (22.4%) 129 (21.3%)\nSerious 2 (0.2%)* 2 (0.3%)*\nFatal 0 0\nMedically -Attended 117 (11.7%) 68 (11.2%)\nLeading  to Study  Discontinuation 0 0\nSevere 2 (0.2%)* 2 (0.3%)*\nAny Adverse  Event  of Special  Interest  (AESI) 0 0\n© 2025  Moderna,  inc. All rights  reserved.\n13\nImmunogenicity  – mRNA -1345  in \nAdults,18 -59 Years,  at Increased  Risk \nof RSV Disease\nStudy  303, Part A\n14\nmRNA -1345  Vaccination  (50 µg) in Adults,18 -59 Years  at \nIncreased  Risk of RSV Disease  Meets  Pre-Specified  Noninferiority \nCriteria  -RSV-A and RSV-B\nStudy  303, Part A & Study  301\nGMR  – Geometric  mean  ratio;  Sept  18, 2024  data  cutoff0.667\nAntibodyGMR  (95%  CI)\nat Month  1\nRSV-A Neutralizing  Antibody  (IU/mL) 1.16 (1.05,  1.29)\nRSV-B Neutralizing  Antibody  (IU/mL) 1.14 (1.04,  1.24)\n0.5 1\nGMR  (95%  CI)2 1.5\n•All GMR  non-inferiority  criteria  met (LB of the 2-sided  95% CI of GMR  > 0.667)\ncomparing  18-59-year -olds vs ≥60-year -olds in efficacy  trial\n© 2025  Moderna,  inc. All rights  reserved.\n15RSV-A Neutralizing  Antibody  GMT  after  50 µg of mRNA -1345  in \nAdults,  18-59 Years,  at Increased  Risk of RSV Disease,  by Age\nStudy  303, Part A\n100000\nRSV-A GMT  comparable  between  18-49 and  50-59 year  olds\n1432164718977 19271\n10010001000018-49 Years  (N=189)  50-59 Years  (N=305)\n© 2025  Moderna,  inc. All rights  reserved.GMT\n(95%  CI)\nRSV-AD1 D29 D1 D29\n16\nRSV-B Neutralizing  Antibody  GMT  after  50 µg of mRNA -1345  in \nAdults,  18-59 Years,  at Increased  Risk of RSV Disease,  by Age\nRSV-B GMT  comparable  between  18-49 and 50-59 year  olds\n93910936678 6745\n100100010000Study  303, Part A\n18-49 Years  (N=189)  50-59 Years  (N=305)\n© 2025  Moderna,  inc. All rights  reserved.GMT\n(95%  CI)\nD1 D29 D1 D29\nRSV-B\n© 2025  Moderna,  inc. All rights  reserved.17\nRSV-A Neutralizing  Antibody  GMT  after  50 µg of mRNA -1345  in Adults,  18-59 \nYears,  at Increased  Risk of RSV Disease  by Primary  Risk Factor  and BMI\nStudy  303, Part A\nGMT;  Geometric  Mean  Titer\n15611678\n1527 15801511 1590 1578148219158 19036 19905\n1678120675 1891520320\n100100010000100000\nGMT \n(IU/mL)All High -Risk \nAdults\n18-59 YearsCoronary \nArtery  Disease/ \nCongestive \nHeart  Failure\n20140BMI < 30\nkg/m2Chronic  Lung  Diabetes \nDiseaseBMI ≥ 30\nkg/m2BMI < 40\nkg/m2BMI ≥ 40\nkg/m2\nD1 D29 D1 D29 D1 D29 D1 D29 D1 D29 D1 D29 D1 D29 D1 D29\nRSV-A\n•Individuals  with medical  risk factors  for RSV show  consistent  RSV-A neutralizing  antibody  responses \ncompared  to entire  study  population;  no impact  of BMI on antibody  response\n•Similar  results  for RSV-B\nGBS – Guillain -Barré  syndrome,  ADEM  – acute  disseminated  encephalomyelitis\n© 2025  Moderna,  inc. All rights  reserved.\n18Summary  – RSV Vaccine  (mRNA -1345)  in Adults, \n18-59 Years,  at Increased  Risk of RSV Disease\n•Vaccine  generally  well tolerated  across  all ages\n•No safety  concerns  identified  (no reports  of thrombocytopenia,  GBS,  ADEM, \nacute  myocarditis  and/or  pericarditis)Safety\n•RSV-A & RSV-B immune  responses  non-inferior  to adults  ≥60 years  in pivotal\nefficacy  trial; similar  efficacy  inferred\n•Immunogenicity  consistent  across  age groups,  including  50-59 years,  and \nunderlying  medical  conditionsImmunogenicity\n•Substantial  burden  of RSV-associated  hospitalizations  in adults,  18-59 years\n•mRNA -1345  has the potential  to also protect  adults,  18-59 years,  at increased \nrisk of severe  RSV disease\n•Data  under  review  by FDA;  PDUFA  date  June  12, 2025Public  Health\nImpact\n© 2025  Moderna,  inc. All rights  reserved.\n19\nRevaccination  of Healthy  Adults \nat 12 or 24 Months\nESCMID  2025\n© 2025  Moderna,  inc. All rights  reserved.\n20RSV Case  Accrual  and Efficacy  Analyses  through  3 Seasons\nin the Phase  2/3 Pivotal  Trial\nStudy  301\n10\n9\n8\n7\n6\n5\n4\n3\n2\n1\n0\n2021  2022  2023  2024\n1. CDC.  Respiratory  Syncytial  Virus  Hospitalization Surveillance  Network  (RSV-NET). https://www.cdc.gov/respiratory -viruses/data -research/dashboard/most -\nimpacted -hospitalizations.html  2. Based  on final FDA Package  InsertOverall  US\n2021 -2023  RSV\nHospitalization \nRate  per \n100,000  Adults\n≥ 65 Years1\n2021 -2022\nRSV Season  12022 -2023\nRSV Season  22023 -2024\nRSV Season  3LRTD  2+\nCasesPrimary  Analysis\nNov ‘21 – Nov ’2285\n174Efficacy2\n50.3%\n(37.5%,  60.7%)LRTD  2+\n62.5%\n(47.7%,  73.1%)78.7%\n(62.8%,  87.9%)\nDurability  through \nSeason  2\nNov ‘21 – Apr ‘23\nDurability  through\nSeason  3\nNov ‘21 – Mar ‘2456.7%\n33.1%,  72.6%)Severe  RSV\n(shortness  of\nbreath)\n74.6%\n(50.7%,  86.9%)86.7%\n(41.9%,  97.0%)\n338\n21\nVaccination  Regimens  – Revaccination  Studies  in Adults\nStudy  302 & Study  301 (50 µg)\nDay 1 12 Months\nRSV Vaccine \n(mRNA -1345)N\nRSV Vaccine \n(mRNA -1345)544\nRSV Vaccine \n(mRNA -1345)1502RSV Vaccine \n(mRNA -1345)24 MonthsRevaccination\nPlaceboStudy  302\n≥50 Years\n© 2025  Moderna,  inc. All rights  reserved.Study  301 \nPart B\n≥60 Years2:1\nVaccine:  Placebo\n12-month  data  presented  at June  2024  ACIP  meeting\n22Revaccination  at 12 Months  with mRNA -1345  Meets \nPre-Specified  Noninferiority  Criteria  -RSV-A\nStudy  302C  – Adults  ≥50 Years  – Per Protocol  Set (N=524)\n214818283\n455419662\n100100010000100000\n1 2 3 4 5 9 10 11 12 13 14\nPart C\n12 Month  Revaccination0\nPart B\nDose  16 7 8\nStudy  MonthRSV-A Neutralizing  Antibody\nGMT\n(IU/mL)\n•RSV-A neutralizing  antibodies  detectable  at 12 months  post-vaccination\n•Revaccination  1 year  after  primary  vaccination  elicits  responses  similar  to those  following  primary  dose\n•Revaccination  met non-inferiority  success  criteria  for RSV-A & RSV-B (LB of 95% CI of GMR  > 0.667)\n© 2025  Moderna,  inc. All rights  reserved.\n23\n© 2025  Moderna,  inc. All rights  reserved.24 Month  Revaccination  – Demographics  of Study  Participants\nStudy  301, Part B, Safety  Set\nmRNA -1345  (50 µg)\nN = 998\nAge (Years) Median  (range) 68.0 (60-91)\nSex, n (%) Female 508 (51%)\nWhite 798 (80%)\nRace/Ethnicity,  n (%)Black  or African  American 161 (16%)\nAsian 14 (1%)\nHispanic  / Latino  Ethnicity 234 (23%)\n≥1 Comorbidity 321 (32%)\nDiabetes  (Type  1 or 2) 194 (19%)\nAsthma 85 (9%)\nComorbidities,  n (%) Chronic  Obstructive  Pulmonary  Disease  (COPD) 54 (5%)\nAdvanced  Liver  or Renal  Disease 11 (1%)\nChronic  Heart  Failure  (CHF) 13 (1%)\nChronic  Respiratory  Disease 2 (0.2%)\nBody  Mass  Index,  n (%) ≥30 kg/m2 317 (32%)\n24\n© 2025  Moderna,  inc. All rights  reserved.Safety  –\nRevaccination  at 24 Months\nSAE – serious  adverse  event;  AESI  – adverse  event  of special  interest \nEnd of study  analysis  (last subject  last visit Oct 23, 2024)\n© 2025  Moderna,  inc. All rights  reserved.\n25\nSafety  - Revaccination  at 24 Months  with mRNA -1345\nStudy  301B,  Adults  ≥60 Years  (N=998)\n•Revaccination  generally  well tolerated\n•Local  and systemic  reactions  were  mainly  Grade  1-2, with median  onset  on\nDay 2, and median  2-day duration\n•Comparable  to reactogenicity  after  primary  dose\n•No safety  concerns  identified\n•No reports  of:\n•Deaths,  SAEs,  or AESIs  as assessed  as vaccine -related  by the investigator\n•Anaphylaxis\n•Guillain  Barre  Syndrome\n•Acute  disseminated  encephalomyelitis  (ADEM)\n•Acute  myocarditis  or acute  pericarditis\n26\n© 2025  Moderna,  inc. All rights  reserved.Immunogenicity  –\nRevaccination  at 24 Months\n27\nRevaccination  at 24 Months  with mRNA -1345  Meets \nPre-Specified  Noninferiority  Criteria  -RSV-A\nStudy  301B  – Adults  ≥60 Years  – Per Protocol  Set (N=956)\n204817157\n417512340\n1000\n100\n0 1 2 3 4 5 6 7 8 9 10  11  12  13  14  15  16  17  18  19  20  21  22  23  24  25  26\nDose  1 Study  Month  24 Month  Revaccination10000100000\nGMT\n(IU/mL)RSV-A Neutralizing  Antibody\n•RSV-A neutralizing  antibodies  detectable  at 24 months  post-vaccination\n•Revaccination  at 24 months  after  primary  vaccination  elicits  responses  similar  to those  following  primary  dose\n•Revaccination  met non-inferiority  success  criteria for  RSV-A & RSV-B (LB of 95% CI of GMR  > 0.667)\n© 2025  Moderna,  inc. All rights  reserved.\n28\nPredicted  Vaccine  Efficacy  for the 12-Month  Period  Following \n24 Month  Revaccination  with mRNA -1345\nNeutralizing  AntibodyDay 29 \nGMT  After\nRevaccination RSV-LRTD  2+ RSV-LRTD  3+\nRSV-A (IU/mL) 1238260%\n(43, 74)68%\n(44, 84)\nRSV-B (IU/mL) 402458%\n(40, 73)67%\n(44, 84)\n0.0 0.2 0.4 0.6 0.8 1.0\nPredicted  Vaccine \nEfficacy  (95%  CI)\n0.0 0.2 0.4 0.6 0.8 1.0\nPredicted  Vaccine \nEfficacy  (95%  CI)\n© 2025  Moderna,  inc. All rights  reserved.Study  P301  Part B Per-Protocol  Set ≥60 Years,  N = 956\nCorrelate  of protection  model  suggests  revaccination  restores  vaccine  efficacy\n29\nSummary  – RSV Vaccine  (mRNA -1345)  Revaccination\n•Revaccination  generally  well tolerated;  no safety  concerns  identified\n•No reports  of GBS,  ADEM,  acute  myocarditis  and/or  pericarditis\n•Durability  of immune  response  demonstrated  out to 24 months\n•Revaccination  at 12 or 24 months:\n•Restores  immune  response;  met noninferiority  criteria\n•Expected  to provide  comparable  vaccine  efficacy  to that after\nprimary  doseSafety  & \nImmunogenicity\n•Revaccination  has the potential  to provide  sustained  protection \nagainst  RSVPublic  Health \nImpact  of \nRevaccination\n© 2025  Moderna,  inc. All rights  reserved.GBS – Guillain -Barré  syndrome,  ADEM  – acute  disseminated  encephalomyelitis\n30\n30\n© 2025  Moderna,  inc. All rights  reserved.THANK  YOU!•Investigators\n•Study  site personnel\n•Laboratory  personnel\n•Most  importantly,  the individuals  who \nparticipated  in these  trials", "summary": "1 © 2025  Moderna,  inc. All rights  reserved.RSV Vaccine  (mRNA -1345)  Update: -Safety  & Immunogenicity  in 18-59 Year  Olds  at increased  Risk for RSV Disease * -Revaccination  of Adults  at 12 or 24 Months * ACIP Frances  Priddy,  MD MPH  April  16, 2025 * mRESVIA  has not been  authorized  for these  indications 2 RSV Vaccine  (mRNA -1345)  Clinical  Development NCT05127434,  NCT05330975,  NCT06060457,  NCT06067230 Efficacy,  Immunogenicity,  Safety,  and Correlate  of Protection…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/02-Priddy-Adult-RSV-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 30}
{"title": "03 Gerber Adult RSV 508", "content": "CO-1\nMeeting of the Advisory Committee on \nImmunization Practices (ACIP)\nCenters for Disease Control and Prevention\nApril 16, 2025\nSusan Gerber, MD\nMedical Director \nGSK\nPresentation by GSK at ACIP April 16, 2025\nCO-2\nAREXVY Indications and Updates\nAREXVY is indicated for active immunization for prevention of lower respiratory tract disease \n(LRTD) caused by RSV in\n▪Individuals ≥ 60 YOA\n▪Individuals 50-59 YOA at increased risk for LRTD caused by RSV\n~ 11 million AREXVY doses administered in US through March *\n*Up to March 2025; YOA, years of age; LRTD: lower respiratory tract disease\nFDA, 2024. AREXVY Prescribing Information (PI); https://www.fda.gov/media/167805/download (URL accessed January 2025) Presentation by GSK at ACIP April 16, 2025\nCO-3\nClinical Development\nPresentation by GSK at ACIP April 16, 2025\nCO-4\nKey Studies in Current US Clinical Development Plan\nPivotal efficacy \nin ≥ 60 YOASafety, immunogenicity, \npersistence and \nrevaccination \nin ≥ 60 YOA Co-administration7–12\nImmunogenicity & \nsafety in 50 -59 YOA \n(incl. AIR)Immunogenicity & \nsafety in \n18-49 YOA AIRImmunogenicity & \nsafety in \nImmunocompromised \n≥ 18 YOA \n(lung and kidney SOT)▪AReSVi -006\n▪Complete▪RSV OA=ADJ -012\n▪Ongoing\n▪Extension of AReSVi -006Safety, immunogenicity, \npersistence and \nrevaccination \nin ≥ 60 YOA \n▪AReSVi -004\n▪Ongoing▪COVID -19 mRNA  vaccine \n(RSV OA=ADJ -013; Ongoing)\n▪PCV20  (RSV OA=ADJ -019; Complete )\n▪HZ/su (RSV OA=ADJ -020; Complete )\n▪FLU-QIV (RSV OA=ADJ -007; Complete )\n▪FLU-aQIV  (RSV OA=ADJ -017; Complete )\n▪FLU-QIV-HD (RSV OA=ADJ -008; Complete )\n▪RSV OA=ADJ -018\n▪Complete▪RSV OA=ADJ -025\n▪Ongoing\n▪RSV OA=ADJ -023\n▪OngoingPhase 2b Phase 3\nAIR, at increased risk; FLU -aQIV , adjuvanted quadrivalent influenza vaccine; FLU -QIV, quadrivalent influenza vaccine; FLU -QIV-HD, high -dose quadrivalent influen za vaccine;\nHZ/su, herpes zoster recombinant subunit vaccine; PCV20, 20 -valent pneumococcal conjugate vaccine; \nSOT, solid organ transplant; YOA, years of age; All studies ClinicalTrials.gov; All URLs accessed February 2025 Presentation by GSK at ACIP April 16, 2025\nCO-5\nImmunogenicity of AREXVY in Adults ≥ 60 YOA Evaluated in \nTwo Complementary Trials\nAReSVi -006 RSV 1 Dose \n(N=12,468) \nAReSVi -006 Placebo \nCrossover (N=12,498)M48 Revaccination (N≈1,000)Timepoint   D1 M13 M24 M25 M60 M12 M36 M37 M48 M49Final End of \nStudy analysisRSV OA=ADJ -012 AReSVi -004Completed\nRSV 1 Dose (N≈330)\nRSV M12, M24 \nRevaccination (N≈990)\nRSV M24 Revaccination \n(N≈330)R RSV 1 dose (N≈1,000) AReSVi -006\nCrossover F irst Dose RSVPreF3 + AS01E (N≈6,600)\nAll studies available on clinicaltrials.gov; All URLs accessed April 2025. Presentation by GSK at ACIP April 16, 2025All participants followed for safety\nRSVPreF3 + AS01E\nPlaceboAReSVi -004 / RSV OA=ADJ -012\nR M36 Revaccination (N≈1,000)\nRSV M36 revaccination (N≈100)\nRSV 1 dose (N≈125)D31\nCO-6\nAReSVi -004: Immunogenicity and Persistence of Single \nDose of AREXVY Vaccine and Different Revaccination \nSchedules in Adults ≥ 60 YOA\nRandomized, open -label, multi -country study (NCT04732871)\nPreliminary updated results\nPresentation by GSK at ACIP April 16, 2025\nCO-7\nRSV-A and RSV -B Neutralizing Antibody Titers After \n12-, 24-, and 36 -Month Vaccination Intervals \nRSV M12, M24 Revaccination RSV M24 Revaccination RSV 1 Dose RSV M36 Revaccination\n1000.010000.0\nGMT (ED60)\n[95%CI]\nM\n6M\n12M\n18M\n24M\n25M\n13D\n31D\n1M\n36M\n37M\n301000.010000.0\nM\n6M\n12M\n18M\n24M\n25M\n13D\n31D\n1M\n36M\n37M\n30\nTimepoint TimepointGMT (ED60)\n[95%CI]RSV-A Serum Neutralization Titers RSV-B Serum Neutralization Titers\nRSV 1 dose (N=112 -121): Participants receiving single dose (Dose 1) of RSVPreF3 + AS01E at Day 1; RSV M12, M24 revaccination (N=247 -341): Participants receiving first dose (Dose 1) of RSVPreF3 + \nAS01E at Day 1, followed by revaccination doses at 12 months and 24 months post Dose 1; RSV M24 revaccination (N=223 -318): Participan ts receiving first dose (Dose 1) of RSVPreF3 + AS01E at Day 1 \nfollowed by revaccination dose at 24 months post Dose 1; RSV M36 Revaccination (N=98 -107): Participants receiving first dose (Do se 1) of RSVPreF3 + AS01E at Day 1, followed by revaccination dose \nat 36 months post Dose 1. ED, estimated dilution; GMT, geometric mean titerAReSVi -004\nPresentation by GSK at ACIP April 16, 2025\nCO-8\nRSVPreF3 -Specific CD4+ T -Cells*: Consistent Responses \nPost Each Vaccination Dose \nRSVPreF3 \nCD4+ T-cells, /106 cells\n(geometric mean [95% CI])\n0.0500.01000.01500.02000.02500.03000.0\nM\n6M\n12M\n18M\n24M\n25M\n13D\n31D\n1M\n36M\n37M\n30\nTimepoint\n*Expressing ≥ 2 activation markers including ≥ 1 cytokine among CD40L, 4 -1BB, IL -2, TNF -a, IFN -g, IL-13, IL -17; RSV 1 dose (N=31 -42): Participants receiving single dose (Dose 1) of RSVPreF3 + AS01E \nat Day 1; RSV M12, M24 revaccination (N=215 -286): Participants receiving first dose (Dose 1) of RSVPreF3 + AS01E at Day 1, followed by revaccination doses at 12 months and 24 months post Dose 1; \nRSV M24 revaccination (N=68 -88): Participants receiving first dose (Dose 1) of RSVPreF3 + AS01E at Day 1 followed by revaccination dose at 24 months post Dose 1; RSV M36 Revaccination (N=31 -\n37): Participants receiving first dose (Dose 1) of RSVPreF3 + AS01E at Day 1, followed by revaccination dose at 36 months post Dose 1. \nCD, cluster of differentiation; IL, interleukin; NAb, neutralizing antibody; TNF, tumor necrosis factorAReSVi -004\nRSV M12, M24 Revaccination RSV M24 Revaccination RSV 1 Dose RSV M36 Revaccination\nPresentation by GSK at ACIP April 16, 2025\nCO-9\nRSV OA=ADJ -012: I mmunogenicity  of Different Revaccination \nSchedules and Persistence of a Single Dose of AREXVY Vaccine \nin Adults Aged ≥ 60 YOA Who Participated in Pivotal AReSVi -006 \nEfficacy Study\nOpen -label extension and crossover study (NCT06534892)\nPreliminary results\nPresentation by GSK at ACIP April 16, 2025\nCO-10\nRSV-A and RSV -B NAb Titers After Initial Dose and 36 -Month \nRevaccination Similar Regardless of Comorbidities of Interest* \n100100010000\nGMT \n(ED60)\n[95%CI]\n\\\n100100010000\n\\M\n12M\n24D\n31M\n36M\n37\nTimepointM\n12M\n24D\n31D\n1M\n36M\n37\nTimepoint≥1 comorbidity of interest* Overall No comorbidity\n*COPD, asthma, any chronic respiratory/pulmonary disease, diabetes type 1 or type 2, chronic heart failure, advanced liver or renal disease; ED, estimated dilution; GMT, geometric mean titer; NAb, \nneutralizing antibody; 1. Unpublished data; 2. Feldman RG et al. Clin Infect Dis  2024;  Day 1 to M12: All participants who received one dose of RSVPreF3 + AS01E in AReSVi -006 ( Immunosubset ); M24: \nAll participants randomized into RSV_1dose group ( Immunosubset ) in AReSVi -006 who did not receive additional doses of vaccine; \nM36 - M37: All participants who received second dose of RSVPreF3 + AS01E approximately 36 Months post -primary dose Presentation by GSK at ACIP April 16, 2025RSV-A Serum Neutralization Titers RSV-B Serum Neutralization Titers\nGMT \n(ED60)\n[95%CI]AReSVi -006 / RSV OA=ADJ -012\n544\n328519\n315416\n246180\n94552\n412535\n379\n872 834 662 274 964 914No comorbidity (n)\n≥ 1 comorbidity (n)\nOverall (n)544 519 417 180 552 535\n328 315 246 94 412 379\n872 834 663 274 964 914D\n1\nCO-11\n100100010000\n100100010000RSV-A and RSV -B NAb Titers After Initial Dose and 36 -Month \nRevaccination Similar Regardless of Frailty Status\n\\M\n12M\n24D\n31D\n1M\n36M\n37\\M\n12M\n24D\n31D\n1M\n36M\n37\nED, estimated dilution; GMT, geometric mean titer; NAb, neutralizing antibody; Unpublished data; Day 1 to M12: All participants who received one dose of adjuvanted RSVPreF3 vaccine in RSV \nOA=ADJ -006 ( Immunosubset ); M24: All participants randomized into the RSV_1dose group ( Immunosubset ) in RSV OA=ADJ -006 who did not receive additional doses of vaccine; \nM36 - M37: All participants who received a second dose of adjuvanted RSVPreF3 vaccine approximately 36 Months post -primary doseRSV-A Serum Neutralization Titers RSV-B Serum Neutralization Titers\nGMT \n(ED60)\n[95%CI]GMT \n(ED60)\n[95%CI]Overall Frail Pre-frail Fit\nTimepoint Timepoint16\n38214\n35515\n2875\n11121\n39719\n374\n474 465 360 158 541 516Frail (n)\nPre-frail (n)\nFit (n)\n872 834 662 274 964 914 Overall (n)16 14 15 5 21 19\n382 355 287 111 397 374\n361 158 541 516 474 465\n872 834 663 274 964 914AReSVi -006 / RSV OA=ADJ -012\nPresentation by GSK at ACIP April 16, 2025\nCO-12\nIncrease in RSV -A and RSV -B NAb Titers Following Revaccination \nwith AREXVY at 36 Months Across Pre -Revaccination Levels\n110100100010000100000Pre-revaccination\n(Month 36 )Post-revaccination\n(Month 37 )\n1 2 3\nQuartile*\nN 225 227 226 2264110100100010000100000\n1 2 3\nQuartile*\nN 226 226 226 2264\n*Participants grouped into quartiles depending on pre -revaccination NAb titers . Participants in quartile 1 had lowest pre -revaccination NAb and those in quartile 4 had highest; \nParticipants receiving first dose (Dose 1) of RSVPreF3 + AS01E at Day 1 (in AReSVi -006 study) followed by revaccination \ndose at 36 months post Dose 1 (in RSV OA=ADJ -012 study); ED, estimated dilution; GMT, geometric mean titer; NAb, neutralizing antibody\nUnpublished data Presentation by GSK at ACIP April 16, 2025RSV-A Serum Neutralization Titers RSV-B Serum Neutralization TitersRSV OA=ADJ -012\n4.9 3.1 2.3 1.5Fold increase \n(by GMTs)\nGMT \n(ED60)\n[95%CI]GMT \n(ED60)\n[95%CI]4.7 2.9 2.5 1.6Fold increase \n(by GMTs)\nCO-13\nLower Pre -Revaccination RSV -A and RSV -B NAb Titers \nAssociated with Higher Seroresponse  Rates (≥ 4 -Fold Increase) \nAfter Revaccination at 36 Months \nParticipants with \n≥ 4-fold increase in \nRSV-B NAb titers  at \nM37 vs M36\n[95% CI]\n0%20%40%60%80%100%\n0 1 2 3 422.6\n(17.3, 28.6)\n8.8\n(5.5, 13.3)29.6\n(23.8, 36.1)52.7 \n(45.9, 59.3)\n1 2 3 4\nQuartile*Participants with \n≥ 4-fold increase in \nRSV-A NAb titers  at \nM37 vs M36\n[95% CI]\n0%20%40%60%80%100%\n0 1 2 3 418.1\n(13.3, 23.8)\n7.5\n(4.4, 11.8)33.9\n(27.8, 40.5)56.9\n(50.1, 63.5)\n1 2 3 4\nQuartile*\nn / N 128 / 225 77 / 227 41 / 226 17 / 226RSV OA=ADJ -012\n*Participants grouped into quartiles depending on pre -revaccination NAb titers . Participants in quartile 1 had lowest pre -revaccination NAb and those in quartile 4 had highest; \nParticipants receiving first dose (Dose 1) of RSVPreF3 + AS01E at Day 1 (in AReSVi -006 study) followed by revaccination \ndose at 36 months post Dose 1 (in RSV OA=ADJ -012 study); NAb, neutralizing antibody Presentation by GSK at ACIP April 16, 2025RSV-A Serum Neutralization Titers RSV-B Serum Neutralization Titers\nn / N 119 / 226 67 / 226 51 / 226 20 / 226\nCO-14\nAReSVi -004 and RSV OA=ADJ -012: Safety Results\nPreliminary updated results\nPresentation by GSK at ACIP April 16, 2025\nCO-15\n0%20%40%60%80%100%Safety and Reactogenicity Profile in Individuals Revaccinated \nat Month 36 Similar to First Dose\nSolicited AEs reported within 4 days of each vaccine dose (Exposed Set)\n% of \nParticipants\n[95% CI]Grade 3\nArthralgia Fatigue Fever Headache Myalgia Erythema Pain Swelling\nUnsolicited AEs, SAEs, Fatal SAEs and pIMDs  of individuals who were revaccinated at Month 36 also similar to those vaccinated at Day 1LocalRSV M36 Revaccination\n(Day 1 Dose)RSV M36 Revaccination \n(M36 Dose)\n4.615.164.8\n57.5\n2.87.514.817.932.434.0\n1.93.821.3 20.832.435.8M36 Revac\n(Day 1)\nM36 Revac\n(M36)\nM36 Revac\n(Day 1)\nM36 Revac\n(M36)\nM36 Revac\n(Day 1)\nM36 Revac\n(M36)\nM36 Revac\n(Day 1)\nM36 Revac\n(M36)\nM36 Revac\n(Day 1)\nM36 Revac\n(M36)\nM36 Revac\n(Day 1)\nM36 Revac\n(M36)\nM36 Revac\n(Day 1)\nM36 Revac\n(M36)\nM36 Revac\n(Day 1)\nM36 Revac\n(M36)AReSVi -004\nRSV 36M revaccination: Participants receiving the first dose (Day 1 Dose) of RSVPreF3 + AS01E at Day 1 followed by a revaccination dose at 36 months (M36 Dose) post -Dose 1. \nGrade 3: >100 mm for erythema and swelling; significant pain at rest, prevents normal everyday activities for pain; prevents normal activity for headache, fatigue, myalgia, \nand arthralgia; >39.0 °C (102.2 °F) for fever. AE, adverse event; SAE, serious adverse event; pIMD , potential immune -mediated diseaseSystemic\nPresentation by GSK at ACIP April 16, 2025\nCO-16\n39.3\n31.7\n2.235.5\n27.9\n2.3\n0%20%40%60%80%100%\n▪Safety profile after revaccination of AREXVY acceptable and consistent with first dose in RSV OA=ADJ -012\n▪No events of GBS or ADEM reported in RSV OA=ADJ -012Safety Profile of Revaccination at Month 36 Similar to \nFirst -Vaccination Dose in Crossover Group RSV OA=ADJ -012\nPresentation by GSK at ACIP April 16, 2025Grade 3\nAny unsolicited AE within \n30 days post -vaccinationM36 Revaccination\n(N = 993)Crossover \nFirst Dose RSVPreF3 + AS01E \n(N = 6,638)\nAny vaccine -related unsolicited AE \nwithin 30 days post -vaccinationAny SAE up to 6 months \npost -vaccinationParticipants \nReporting \nEvent \n(95% CI)\n*Solicited AEs not collected in RSV OA=ADJ -012\nCO-17\nSummary: AReSVi -004 and RSV OA=ADJ -012\nRobust humoral and cellular immune responses observed with AREXVY revaccination\n▪Humoral immune responses similar among participants with ≥ 1 comorbidity of interest or \nfrailty status compared to overall population\n▪RSV neutralizing antibody responses observed after revaccination at 36 -month interval \nsimilar to RSV neutralizing antibody responses after revaccination at 24 -month interval\n▪The lower the pre -revaccination RSV -A and RSV -B neutralizing titers, the higher the \nseroresponse  rates after revaccination at 36 months\nSafety and reactogenicity of revaccination is similar as compared with first dose\nPresentation by GSK at ACIP April 16, 2025\nCO-18\n224403757\n0100200300400500600700800\nRSV-Related DeathsRSV Outcomes Estimated to be Avoided with Vaccination vs \nNo Vaccination Over 3 Years Based on Vaccine Efficacy Results \nfrom AReSVi -006 (30.6 -Month Median Follow Up)\n3,1835,7369,838\n02,0004,0006,0008,00010,00012,000\nRSV-Related Hospitalizations\nPresentation by GSK at ACIP April 16, 2025Estimates are based on GSK modeling that synthesized multiple published and public sources, and involved assumptions to infor m certain parameters, including variability in RSV -related mortality \nby age. Key references for model inputs include: Singer et al., Poster Presentation at RSV Symposium 2025; La et al., Human V accines & Immunotherapeutics , 2024; Branche et al., Clin Infect Dis, \n2022; McLaughlin et al., Open Forum Infect Dis, 2022;  Tseng et al., J Infect Dis, 2020 ; Ison et al., Poster Presentation at CHEST 2024 . \nCOPD = chronic obstructive pulmonary disease; YOA = years of ageDiabetes COPD Heart Failure\nEstimated RSV \nOutcomes \nAvoided\nper 1 Million \nAREXVY \nVaccinations \nAmong Adults \n50-59 YOA\nCO-19 \nConclusion\nPresentation by GSK at ACIP April 16, 2025\nReal world vaccine effectiveness data, along with ongoing immunogenicity studies, \nwill inform optimal revaccination timing\n~13 million US adults 50 -59 YOA  at risk for severe RSV disease\n▪Over 3 years, vaccination with AREXVY* may help prevent an estimated \n▪~3,218 hospitalizations in individuals with heart failure\n▪~8,638 hospitalizations in individuals with COPD\n▪~8,164 hospitalizations in individuals with diabetes\nEvidence to support revaccination with AREXVY\n▪Robust humoral and cellular immune responses following revaccination at \n24 and 36 -month intervals\n▪Lower pre -revaccination titers elicit higher seroresponse  rates after revaccination\n▪Safety and reactogenicity of revaccination is similar as compared with first dose\n*Based on GSK modeling 46.2% uptake = flu vaccine uptake in group\nCO-20\nMeeting of the Advisory Committee on \nImmunization Practices (ACIP)\nCenters for Disease Control and Prevention\nApril 16, 2025\nSusan Gerber, MD\nMedical Director \nGSK\nPresentation by GSK at ACIP April 16, 2025\nCO-21\n•AREXVY is contraindicated in anyone with a history of a severe allergic reaction ( eg, anaphylaxis) to any \ncomponent of AREXVY\n•The results of a postmarketing  observational study suggest an increased risk of Guillain -Barré syndrome during the \n42 days following vaccination with AREXVY\n•Appropriate medical treatment must be immediately available to manage potential anaphylactic reactions following \nadministration of AREXVY\n•Syncope (fainting) may occur in association with administration of injectable vaccines, including AREXVY . \nProcedures should be in place to avoid injury from fainting\n•Immunocompromised persons, including those receiving immunosuppressive therapy, may have a diminished \nimmune response to AREXVY\n•In adults 60 years of age and older, the most commonly reported adverse reactions (≥10%) were injection site pain \n(60.9%), fatigue (33.6%), myalgia (28.9%), headache (27.2%), and arthralgia (18.1%)\n•In adults 50 through 59 years of age, the most commonly reported adverse reactions (≥10%) were injection site pain \n(75.8%), fatigue (39.8%), myalgia (35.6%), headache (31.7%), arthralgia (23.4%), erythema (13.2%), and swelling \n(10.4%)\n•There are no data on the use of AREXVY in pregnant or breastfeeding individuals. AREXVY is not approved for use \nin persons <50 years of age\n•Vaccination with AREXVY may not result in protection of all vaccine recipientsAREXVY Important Safety InformationAREXVY Indication\nAREXVY is a vaccine indicated for active immunization for the prevention of lower respiratory tract disease (LRTD) \ncaused by respiratory syncytial virus (RSV) in:\n•individuals 60 years of age and older;\n•individuals 50 through 59 years of age who are at increased risk for LRTD caused by RSV", "summary": "CO-1 Meeting of the Advisory Committee on  Immunization Practices (ACIP) Centers for Disease Control and Prevention April 16, 2025 Susan Gerber, MD Medical Director  GSK Presentation by GSK at ACIP April 16, 2025 CO-2 AREXVY Indications and Updates AREXVY is indicated for active immunization for prevention of lower respiratory tract disease  (LRTD) caused by RSV in ▪Individuals ≥ 60 YOA ▪Individuals 50-59 YOA at increased risk for LRTD caused by RSV ~ 11 million AREXVY doses administered in US…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/03-Gerber-Adult-RSV-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 21}
{"title": "04 Ortega Sanchez Adult RSV 508", "content": "This slide deck was prepared by Dr. David Hutton \nof the University of Michigan and reflects his work. \nIt is being presented by CDC staff on his behalf. Dr. \nHutton will be available to answer questions at the \nend of this presentation. \n1\nEconomic Analysis of Protein Subunit \nand mRNA RSV Vaccination in Adults \naged 50 -59 Years\nDavid W. Hutton, PhD, MS\nAssociate Professor, Health Management and Policy, School of Public Health\nAssociate Professor of Global Public Health, School of Public Health\nAssociate Professor, Industrial and Operations Engineering, College of Engineering\nUniversity of Michigan\n2This slide deck was prepared by Dr. David Hutton of the University of Michigan and reflects his work. It is being \npresented by Dr. Ismael Ortega -Sanchez (CDC) on his behalf. \nPresentation for the Advisory Committee on Immunization Practices, April 16th, 2025\nResearch Team\nUniversity of Michigan\n•David Hutton, PhD\n•Lisa Prosser, PhD\n•Angela Rose, MPH\n•Christina Nyamuswa , MSCDC\n•Michael Melgar, MD\n•Amadea Britton, MD \n•Lauren Roper, MPH\n•Mila Prill, MSPH\n•Amber Kautz, PhD\n•Jamison Pike, PhD\n•Ismael Ortega -Sanchez, PhD\n•Andrew Leidner, PhD\n•Fiona Havers, MD\n•Michael Whitaker, MPH\n•Rebecca Woodruff, PhD\n•Gordana Derado, PhD\n•Huong Pham, MPH\n3\nConflicts of interest  statements\n•No known conflict of interests.\n4\nStudy Question\n•Evaluate the Cost -Effectiveness of RSV vaccination \n•Compare vaccination to no vaccination using an incremental cost -effectiveness \nratio\n•Scenario Analyses\n•Perspective: Societal\n•Focus: Age 50 -59 \n•We will show some results for other age groups as well\n5\nMethods\n6\nMethods: Intervention(s)\n•Target population: US adults aged ≥50 years, stratified by age, chronic \nmedical conditions\n•Adults aged 50 -59 years with at least one chronic medical condition*\n•Adults aged 60 -74 years with at least one chronic medical condition*\n•Adults aged ≥75 years\n•Interventions: RSV vaccination \n•Protein subunit RSV vaccination (Pfizer’s ABRYSVO, GSK’s AREXVY)\n•Moderna RSV vaccination (Moderna’s mRESVIA )\n•Each compared to no vaccination\n7*For base case, at least one of: chronic obstructive pulmonary disease (COPD), asthma, coronary artery disease, chronic \nkidney disease, diabetes mellitus, severe obesity (BMI ≥40)\nMethods: Decision Tree Model\n8No \nVaccination\nVaccinationInfection Hospitalization\nED\nNone of the aboveOutpatientAlive\nDead\nBox A.  RSV Infection\nMethods: Decision Tree Model\n9No \nVaccination\nVaccinationInfection Hospitalization\nED\nNone of the aboveOutpatientAlive\nDead\nBox A.  RSV Infection\nAdverse \nEventsSystemic Reaction\nInjection Site Reaction\nNone of the aboveSerious Adverse EventGuillain Barre Syndrome\nMethods: Decision Tree Model\n10No \nVaccination\nVaccinationInfection Hospitalization\nED\nNone of the aboveOutpatientAlive\nDead\nBox A.  RSV Infection\nAdverse \nEventsSystemic Reaction\nInjection Site Reaction\nNone of the aboveSerious Adverse EventInfection Box A. RSV Infection in each node : same \nstructure as above, but with risks reduced, \naccording to vaccine effectiveness \nGuillain Barre Syndrome\nAnnual RSV incidence\n•At least one chronic medical condition (source RSV -NET and the Behavioral Risk Factor \nSurveillance System [BRFSS]):\n•Chronic obstructive pulmonary disease (COPD), OR\n•Asthma, OR\n•Coronary artery disease (CAD), OR\n•Diabetes mellitus, OR\n•Chronic kidney disease (CKD), OR\n•Severe obesity (body mass index [BMI] ≥40 kg/m2)\n•Additional chronic medical conditions evaluated in scenario analyses:\n•Heart failure1\n•Immune compromised\n•Lung transplant2\n•Hematopoietic cell transplant, allogeneic3,4\n•Hematopoietic cell transplant, autologous3,4\n1. Kujawski  SA, et al. Rates of respiratory syncytial virus (RSV) -associated hospitalization among adults with congestive heart failure -United States, 2015 -2017. PLoS  One. 2022 Mar \n9;17(3):e0264890. doi: 10.1371/journal.pone.0264890\n2. Testaert  H, et al. Incidence, management and outcome of respiratory syncytial virus infection in adult lung transplant recipients: a 9 -year retrospective multicentre  study. Clin Microbiol  \nInfect. 2021 Jun;27(6):897 -903. doi: 10.1016/j.cmi.2020.07.050.\n3. Martino R, et al. Prospective study of the incidence, clinical features, and outcome of symptomatic upper and lower respirato ry tract infections by respiratory viruses in adult \nrecipients of hematopoietic stem cell transplants for hematologic malignancies. Biol Blood Marrow Transplant. 2005 Oct;11(10) :781-96. doi: 10.1016/j.bbmt.2005.07.007\n4. Waghmare A, et al. Supplemental Oxygen -Free Days in Hematopoietic Cell Transplant Recipients With Respiratory Syncytial Virus. J  Infect Dis. 2017 Dec 5;216(10):1235 -1244. doi: \n10.1093/ infdis /jix390These conditions  are considered separately \nbecause RSV epidemiologic parameters were \nderived from different published sources and \ncannot be combined with RSV -NET hospitalization \nrate estimates under “at least one” condition.\n11\nAnnual RSV incidence\n•At least one chronic medical condition (source RSV -NET and the Behavioral Risk Factor \nSurveillance System [BRFSS]):\n•Chronic obstructive pulmonary disease (COPD), OR\n•Asthma, OR\n•Coronary artery disease (CAD), OR\n•Diabetes mellitus, OR\n•Chronic kidney disease (CKD), OR\n•Severe obesity (body mass index [BMI] ≥40 kg/m2)\n•Additional chronic medical conditions evaluated in scenario analyses:\n•Heart failure1\n•Immune compromised\n•Lung transplant2\n•Hematopoietic cell transplant, allogeneic3,4\n•Hematopoietic cell transplant, autologous3,4\n121. Kujawski  SA, et al. Rates of respiratory syncytial virus (RSV) -associated hospitalization among adults with congestive heart failure -United States, 2015 -2017. PLoS  One. 2022 Mar \n9;17(3):e0264890. doi: 10.1371/journal.pone.0264890\n2. Testaert  H, et al. Incidence, management and outcome of respiratory syncytial virus infection in adult lung transplant recipients: a 9 -year retrospective multicentre  study. Clin \nMicrobiol  Infect. 2021 Jun;27(6):897 -903. doi: 10.1016/j.cmi.2020.07.050.\n3. Martino R, et al. Prospective study of the incidence, clinical features, and outcome of symptomatic upper and lower respirato ry tract infections by respiratory viruses in \nadult recipients of hematopoietic stem cell transplants for hematologic malignancies. Biol Blood Marrow Transplant. 2005 Oct; 11(10):781 -96. doi: \n10.1016/j.bbmt.2005.07.007\n4. Waghmare A, et al. Supplemental Oxygen -Free Days in Hematopoietic Cell Transplant Recipients With Respiratory Syncytial Virus. J  Infect Dis. 2017 Dec 5;216(10):1235 -1244. doi: \n10.1093/ infdis /jix390Assumed that vaccine effectiveness \nwas reduced by half  in immune \ncompromised populations, compared \nwith all others\nVaccine effectiveness (VE) of a single dose over time: \nprotein subunit RSV vaccine (combined Pfizer/GSK)\n13Linear decay to \n0% by 36 months\nVE against hospitalization and emergency department visits was assumed to be equal to results of a meta -analysis of observational V E estimates from CDC, FDA/CMS, Veteran’s \nHealth Administration, and Pfizer analyses from the first RSV season of vaccine availability. VE against outpatient illness w as assumed to be the mean across the two products of \ntrial efficacy against RSV acute respiratory illness.3-year projected effectiveness against ED and hospitalization based \non a meta -analysis of real -world vaccine effectiveness studies. Base \ncase truncated at 36 months based on available clinical follow -up \nextending only through 3 RSV seasons for a subunit vaccine. \n68%\n39%78%\n59%\n45%82%\n62%\n48%\n0%10%20%30%40%50%60%70%80%90%100%\n0 6 12 18 24 30 36Effectiveness\nMonths since vaccination\nOutpatient ED Hospitalization\nUnlike for protein subunit RSV vaccines, there are \nstill no published vaccine effectiveness results for \nModerna’s mRNA RSV vaccine.\nAll effectiveness assumptions in this model are \nderived from clinical trial efficacy against \nsymptomatic disease. Median clinical trial follow up \ndoes not extend beyond 2 years per participant.\n14\nVaccine effectiveness (VE) of a single dose over time \nbase case : mRNA Moderna RSV vaccine ( mRESVIA )\n15Linear decay to 0% by \n24 months\nVE against emergency department visits and hospitalization was assumed to be equal to clinical trial vaccine efficacy against  RSV lower respiratory tract disease with ≥2 \nsigns/symptoms. VE against outpatient illness was assumed to be equal to clinical vaccine efficacy against medically attended  RSV acute respiratory illness. VE was assumed to \ndecline to zero by month 24 post -vaccination.2-year projected effectiveness based on trial efficacy data through 24 \nmonths of follow -up (no real -world effectiveness data exists). \nDuration of protection may extend beyond 24 months, but base case \ntruncated at 24 months based on available clinical follow -up \nextending only through a median of <24 months per participant. \n68%\n44%84%\n38%\n30%\n0%10%20%30%40%50%60%70%80%90%100%\n0 6 12 18 24 30 36Effectiveness\nMonths since vaccination\nOutpatient ED and Hospitalization\nVaccine effectiveness (VE) of a single dose over time \nscenario analysis : mRNA Moderna RSV vaccine ( mRESVIA )\n3-year projected effectiveness based on waning model developed \nby Moderna  using clinical trial efficacy at multiple time points (no \nreal -world effectiveness data exists). In this model effectiveness is \nprojected to extend for 3 RSV seasons. \nOrange line: VE: RSV -LRTD\nBlue line: VE: RSV -ARD\nModerna performed a weighted least square regression on VE data estimated every 2 months, through 18 months68%84%\n0%10%20%30%40%50%60%70%80%90%100%\n0 6 12 18 24 30 36Effectiveness\nMonths since vaccination\nOutpatient ED and Hospitalization\n16\nMethods Updates\nSame model presented in June 2024 and October 2024, with the \nfollowing changes:\n•Costs\n•Costs for those under 65 based on an analysis using MarketScan  by Averin  et al.\n•Marketscan  (all of US)\n•Matched adults 18+, also reports by chronic condition\n•Averin  et al analysis was conducted using final support from Pfizer Inc\n•Costs for those 65 and older based on a CDC analysis of Medicare data\n•Corrected productivity calculation for ages 50 -64\n•Vaccine Effectiveness\n•Subunit 36 months of efficacy\n•Moderna long -term efficacy assumption\n•Mortality\n•Guillain Barre Syndrome (GBS)\nAverin  A, Atwood M, Sato R, Yacisin  K, Begier  E, Shea K, Curcio D, Houde  L, Weycker  D. Attributable Cost of Adult Respiratory Syncytial Virus Illness Beyond the Acute Phase. In \nOpen Forum Infectious Diseases 2024 Mar (Vol. 11, No. 3, p. ofae097). US: Oxford University Press.17\nGuillain -Barre Syndrome (protein subunit \nvaccines only)\n•Base: FDA analysis of adults 65+ with rates ranging between 0 – 18 excess \ncases per million doses administered\n•Scenario:\n•Baseline GBS rates in U.S. adults 50 -64 (assumed same for adults 50 -59 in the model)\n•25.2 per million person -years (combined male, female)\n•2021 study of 50 million person -years of observation1\n•Inpatient and emergency department results, adjusted downward by the positive predictive \nvalue (55%) of ICD codes in identifying “true” GBS in inpatient/ED.\n•Relative measures of GBS risk from protein subunit RSV vaccination applied relative to \nthe assumed 50 -59 baseline to see what happens if risk is lower in younger adults2\n•GSK: Incidence rate ratio (IRR) = 2.46 (95% CI 1.19 – 5.08)\n•Pfizer: IRR = 2.02 (95% CI 0.93 – 4.40)\n•42-day risk window used in FDA’s analysis.\n•Net Excess 42 -day risk of 3.6 per million doses (average of Pfizer and GSK)\n1. Shui IM, Rett MD, and Weintraub E et al. Guillain -Barré syndrome incidence in a large United States cohort (2000 -2009). \nNeuroepidemiology. 2012;39(2):109 -15. doi: 10.1159/000339248. Epub  2012 Jul 28. PMID: 22846726. \n2. Package inserts: GSK, Pfizer.18\nMethods: Additional Inputs\n•Also included \n•RSV illness QALYs lost\n•RSV illness productivity costs\n•Vaccination healthcare and productivity costs\n•Vaccination adverse events\n•Medical costs\n•Productivity costs\n•These assumptions remain unchanged from October 2024\n19Hutton, 2023. “Economic Analysis of RSV Vaccination in Older Adults”. June 2023 ACIP Meeting  \nHutton et al., 2024. “Cost -effectiveness of vaccinating adults aged 60 years and older against respiratory syncytial virus”. Vaccine  \n42(24): 126294\nMethods: Scenarios\n•Manufacturer -specific (Pfizer and GSK -specific models; Moderna \nis considered separately in the base case, so no scenario needed)\n•For Moderna, assuming longer duration of protection \n(manufacturer 3 -year efficacy assumption)\n•Vaccination of persons without chronic medical conditions \n•Condition -specific (e.g., vaccination of persons with heart failure)\n•Public sector prices for each vaccine (Federal Supply Schedule \nprices from the Veterans Health Administration*), rather than the \nmanufacturer list price\n20 *https://www.vendorportal.ecms.va.gov/NAC/Pharma/List  \nResults\n21\nPrevious (June 2024)  Cost -Effectiveness Results: Societal \ncosts per quality -adjusted life year (QALY) gained\nPreF  subunit vaccines PreF  mRNA vaccines\nAdults aged 50 -59 \n years  with at least \n 1 condition$154,501*\nAdults aged 60 -74 \n years with at least 1 \n condition$60,933 $80,953 \nAll adults aged ≥75   \n years $51,447 $66,287 2-year 2-year\nAt least one condition refers to: chronic obstructive pulmonary disease, asthma, coronary artery disease, diabetes \nmellitus, chronic kidney disease, severe obesity (body mass index [BMI] ≥40)\n*The $154,501 incremental cost -effectiveness ratio (ICER) is GSK -specific, but the other two are for subunit in \ngeneral. 22\nToday’s  Cost -Effectiveness Results: \nSocietal costs per quality -adjusted life year (QALY) gained\nPreF subunit vaccines PreF  mRNA vaccines PreF  mRNA vaccines\nAdults aged 50 -59 \n years  with at least \n 1 condition$43,070 \n(<0-$266,769)$152,293 \n($1,154 -$811,138)$95,182 \n(<0-$682,508)\nAdults aged 60 -74 \n years with at least 1 \n condition$21,721 \n(<0-$120,989)$85,781  \n($3,368 -$409,467)$50,864 \n($3,668 -$249,938)\nAll adults aged ≥75   \n years$45,769 \n($25,505 -$84,871)$100,571  \n($58,277 -$225,885)$70,731 \n($42,069 -$159,451)3-year 2-year 3-year\nAt least one condition refers to: chronic obstructive pulmonary disease, asthma, coronary artery disease, \ndiabetes mellitus, chronic kidney disease, severe obesity (body mass index [BMI] ≥40)\nRanges reflect 2.5th and 97.5th percentile from Monte Carlo simulation.\n“<0” represents cost -saving (lower costs, improved health/QALYs) 23\nOutcome Subunit \n(3-year)mRNA \n(2-year)mRNA \n(3-year)\nOutpatient 43 56 62 \nHospitalization 510 933 681 \nDeath 7,985 14,620 10,675 Number Needed to Vaccinate to Prevent One Outpatient Visit, \nHospitalization, or Death\nAge 50 -59 years with at least one condition\nAt least one condition refers to: chronic obstructive pulmonary disease, asthma, coronary artery disease, \ndiabetes mellitus, chronic kidney disease, severe obesity (body mass index [BMI] ≥40)\n24\nScenario Analyses\n25\nScenario:  Cost -Effectiveness Results Using Veterans \nAffairs (VA) Federal Supply Schedule (FSS) Vaccine Prices:\nSocietal costs per quality -adjusted life year (QALY) gained\nSubunit RSV \nvaccinePreF  mRNA vaccines PreF  mRNA vaccines\nAdults aged 50 -59 \n years  with at least \n 1 condition$25,967 $79,443 $37,082\nAdults aged 60 -74 \n years with at least 1 \n condition  $12,122   $43,670  $18,380\nAll adults aged ≥75   \n years \n $37,536  $64,251 $42,8823-year 2-year 3-year\nVA Federal Supply Schedule prices used in lieu of list prices ( VA National Acquisition Center Contract Catalog Search Tool ): Arexvy  (GSK) \n$263, Abrysvo  (Pfizer) $258, mResvia  (Moderna) $204. \nAt least one condition refers to: chronic obstructive pulmonary disease, asthma, coronary artery disease, diabetes mellitus, chronic kidney disease, \nsevere obesity (body mass index [BMI] ≥40)26\n$0 $25,000 $50,000 $75,000 $100,000 $125,000 $150,000 $175,000 $200,000\nAll Adults\nAt least one condition\n CKD\n COPD\n obesity BMI >40\n Asthma\n CAD\n Diabetes\n Heart Failure\nWith lung transplant\nWith allogenic HCT\nWith autologous HCTIncremental cost per QALY gained \n 50-59\n 60-74\n≥75\nnot age-specificSpecific Chronic Conditions: Subunit\nCKD: chronic kidney disease; COPD: chronic obstructive pulmonary disease; BMI: body mass index; CAD: coronary artery disease;  HCT: hematopoietic cell transplant\n*Indicates cost saving which means net costs are reduced and health outcomes are improved when compared to “no vaccination ”\nAt least one condition refers to: COPD, asthma, CAD, diabetes mellitus, CKD, severe obesity (BMI ≥40)*****\n27**\n*\n**\n*\n**\n*\n**Severe obesity (BMI ≥ 40)\nHeart failure\nSpecific Chronic Conditions: mRNA (2 -year)\nCKD: chronic kidney disease; COPD: chronic obstructive pulmonary disease; BMI: body mass index; CAD: coronary artery disease;  HCT: hematopoietic cell transplant\n*Indicates cost saving which means costs are reduced and health outcomes are improved \nAt least one condition refers to: COPD, asthma, CAD, diabetes mellitus, CKD, severe obesity (BMI ≥40)*\n*\n28**$0 $25,000 $50,000 $75,000 $100,000 $125,000 $150,000 $175,000 $200,000\nAll Adults\nAt least one condition\n CKD\n COPD\n obesity BMI >40\n Asthma\n CAD\n Diabetes\n Heart Failure\nWith lung transplant\nWith allogenic HCT\nWith autologous HCTIncremental cost per QALY gained\n 50-59\n 60-74\n≥75\nnot age-specificSevere obesity (BMI ≥ 40)\nHeart failure\nSpecific Chronic Conditions: mRNA (3 -year)\nCKD: chronic kidney disease; COPD: chronic obstructive pulmonary disease; BMI: body mass index; CAD: coronary artery disease;  HCT: hematopoietic cell transplant\n*Indicates cost saving which means costs are reduced and health outcomes are improved \nAt least one condition refers to: COPD, asthma, CAD, diabetes mellitus, CKD, severe obesity (BMI ≥40)*\n*\n29***\n**\n***$0 $25,000 $50,000 $75,000 $100,000 $125,000 $150,000 $175,000 $200,000\nAll Adults\nAt least one condition\n CKD\n COPD\n obesity BMI >40\n Asthma\n CAD\n Diabetes\n Heart Failure\nWith lung transplant\nWith allogenic HCT\nWith autologous HCTIncremental cost per QALY gained\n 50-59\n 60-74\n≥75\nnot age-specificSevere obesity (BMI ≥ 40)\nHeart failure\nHospitalizations, ICU stays, and deaths preventable \nif 20% of all U.S. adults aged 50 -59 years with at \nleast one chronic condition* were vaccinated\nThe model assumed 0–48 cases of Guillain -Barre Syndrome total\n305,219\n1,148\n3331,793\n394 8910,077\n2,217\n702\n02,0004,0006,0008,00010,00012,000\nHospitalizations ICU Stays DeathsEvents Preventable\n*At least one condition refers to: chronic obstructive pulmonary disease, asthma, coronary artery disease, diabetes mellitus,  chronic kidney disease, \nsevere obesity (body mass index [BMI] ≥40)\nScenario (lower GBS risk in adults aged <65)*: Hospitalizations, \nICU stays, and deaths preventable if 20% of all U.S. adults aged \n50-59 years with at least one chronic condition** were vaccinated\nThe model assumed 1 –29 cases of Guillain -Barre Syndrome total\n*Assuming lower baseline risk of GBS in adults aged 50 -59 years than in adults aged ≥65 years. In this scenario, the relative risk of GBS \nwas applied to published background rates of GBS for this age group.\n**At least one condition refers to: chronic obstructive pulmonary disease, asthma, coronary artery disease, diabetes mellitus, chronic \nkidney disease, severe obesity (body mass index [BMI] ≥40)\n 315,219\n1,148\n3331,793\n394 8910,077\n2,217\n702\n02,0004,0006,0008,00010,00012,000\nHospitalizations ICU Stays DeathsEvents Preventable\nLimitations\n•Model Structure\n•No dynamic transmission. No impact of the vaccine on transmission and \nindirect effects\n•We did not include or analyze all potential RSV risk factors.  \n•Some medical conditions (e.g., interstitial lung disease) are likely associated with \nhigh risk of severe RSV disease, but literature on population -based hospitalization \nrates and other outcomes are lacking.  \n•Uncertain inputs\n•RSV burden of disease, especially hospitalization and mortality\n•RSV costs\n•Caregivers of persons ill with RSV may incur additional productivity losses not included \nin this model\n•Duration and waning pattern of vaccine protection (especially mRNA)\n32\nConclusions\n•Cost -Effectiveness of vaccinating adults 50-59 with at least one \nchronic medical condition:\n•Subunit: $43,070/QALY\n•mRNA: $152,293/QALY (2 -year), $95,182/QALY (3 -year)\n•Vaccinating people with th e following conditions may be cost -saving:\n•Immune compromise, defined as hematopoietic cell transplant or lung transplant\n•Heart failure \n•Chronic obstructive pulmonary disease (COPD)\n•Chronic kidney disease\n•Severe obesity (body mass index [BMI] ≥40) \n•Scenarios with lower prices were more cost -effective\n33\nThank You\n•Please send questions/comments to:\n•dwhutton@umich.edu\n34", "summary": "This slide deck was prepared by Dr. David Hutton  of the University of Michigan and reflects his work.  It is being presented by CDC staff on his behalf. Dr.  Hutton will be available to answer questions at the  end of this presentation.  1 Economic Analysis of Protein Subunit  and mRNA RSV Vaccination in Adults  aged 50 -59 Years David W. Hutton, PhD, MS Associate Professor, Health Management and Policy, School of Public Health Associate Professor of Global Public Health, School of Public…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/04-Ortega-Sanchez-Adult-RSV-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 34}
{"title": "05 Ortega Sanchez Adult RSV 508", "content": "Economics of Respiratory Syncytial Virus \nVaccination in Adults aged 50 -59 years \nat Increased Risk of Severe RSV Disease\nSUMMARY COMPARING MODELS FROM:\nGSK,Moderna ,Pfizer AND University of Michigan -CDC\nIsmael R. Ortega -Sanchez, PhD\nNCIRD/CDC\nACIP Meeting, April 16, 2025\n1Disclaimer : The findings and conclusions in this report are those of the authors and do not necessarily represent the views of \nthe Centers for Disease Control and Prevention. \nConflicts of interest\n•GSK model : David Singer et al.,  [complete list and affiliations, upon request]\n•GSK manufactures the adjuvanted RSVPreF3 (RSVPreF3)  vaccine \n•RTI Health Solutions was funded by GSK\n•Moderna model : Parinaz  Ghaswalla  et al., [complete list and affiliations, upon request]\n•Moderna manufacturers the mRNA -1345 RSV  vaccine\n•Quadrant Health Economics and RTI Health Solutions were funded by Moderna\n•Pfizer  model : Reiko Sato et al., [complete list and affiliations, upon request]\n•Pfizer Inc (PA, USA) manufacturers the bivalent stabilized prefusion F subunit ( RSVpreF ) vaccine\n•Avalere Health (Washington DC, USA) was funded by Pfizer\n•UM-CDC model : David W Hutton et al. from Univ Michigan, …, Ismael R Ortega -Sanchez et al. from CDC \n[complete list and affiliations, upon request ]\n•All authors: No conflicts of interest\n2\nEconomic analysis\nPolicy question : Should a single dose of RSV vaccine (any licensed product)a,b be \nrecommended for adults 50 -59 years old at increased risk of severe RSV disease?\nCost -effectiveness analyses : \n               Comparator      Intervention\nBase -case scenario:  \n•What is the incremental cost-effectiveness  of vaccinating adults aged 50 -59 years \nat increased risk of severe RSV disease relative to no vaccination?\n3No vaccinationVaccination: \nReceipt of one dose of any \nlicensed RSV vaccine\na. GSK and Pfizer vaccines are currently licensed for adults 50 -59 years at increased risk: https://www.fda.gov/vaccines -blood -\nbiologics/arexvy , https://www.fda.gov/vaccines -blood -biologics/abrysvo\nb. Moderna vaccine is not currently licensed in adults aged <60 years: https://www.fda.gov/vaccines -blood -biologics/vaccines/mresvia   \n4Modeling design and assumptions\nGSK Moderna Pfizer UM-CDC\nStatic analytical decision -making models \nSensitivity analyses (and probabilistic simulation)\n (\n)\n (\n)\n (\n)\n (\n)\nHypothetical population: 50 -59 years old at increased risk\nTimeframe after a dose of RSV vaccine (in years)a 5 3 3.5b 3 and 2c\nAnalytic Horizon: Age - and comorbidity -specific life expectancy\n Age only\nDiscount rate: 3% \nYear of economic outcomes measured 2024 2024 2023 2024\nSocietal perspective (and healthcare perspective)\n (\n)\n (\n)\n (\n)\n (\n)\na.Base -case in Moderna, and Pfizer models relied on a three -year timeframe (other timeframes included in scenario analyses) while GSK used a five -year timeframe in the base -case and \nthree -year in scenario. In each model, selection of timeframe is based on the duration of protection assumption.\nb.Although Pfizer base -case relies on a thee -year timeframe, in scenario analyses Pfizer reported outcomes for up to 70 months (>5  years timeframe) duration of vaccine protection.\nc.Base -case in UM -CDC model uses three -year time frame for protein subunit vaccines and a two -year time frame for mRNA vaccine.  However, in a scenario analysis UM -CDC model \nuses a three -year time frame for the mRNA vaccine  \nGSK, Moderna , Pfizer  and UM-CDC models \ncomparison \nWe will compare:\n•Risk conditions included in base -case and scenarios\n•Incidence of RSV hospitalization and outpatient care\n•Medical costs due to RSV illness\n•RSV mortality rate \n•Indirect costs due to RSV illness\n•Quality -adjusted life years lost per RSV illness\n•Initial vaccine effectiveness and waning assumptions\n51st\n2nd\n3rd\n4th \nGSK, Moderna , Pfizer  and UM-CDC models comparison: \nRisk conditions included in base -case and scenarios\n6GSK Moderna Pfizer  UM-CDC\nBase -caseChronic obstructive \npulmonary disease \n(COPD)≥ 1 chronic medical \nconditiona≥ 1 chronic or \nimmunocompromising \nmedical conditionb≥ 1 chronic medical \nconditionc\nIndividual \nconditions \nevaluated in \nscenarios•Asthma\n•Congestive heart failure \n•Coronary artery disease \n•Diabetes mellitus•Asthma\n•COPD\n•Coronary artery disease\n•Congestive heart failure \n•Chronic kidney disease\n•Chronic liver disease\n•Diabetes mellitus \n•Severe obesity (body \nmass index [BMI] ≥40 \nkg/m2)•Cardiovascular disease\n•Pulmonary disease\n•Renal disease\n•Diabetes mellitus\n•Immunocompromising \nconditions (e.g., solid cancer, \nhematological malignancies, \nsolid organ transplant, or \nreceiving immunosuppressive \nmedication)•Asthma\n•COPD\n•Coronary artery disease\n•Chronic kidney disease \n•Diabetes mellitus\n•Severe obesity (BMI ≥40 \nkg/m2)\n•Heart failure\n•Lung transplant\n•Allogeneic hematopoietic \ncell transplant\n•Autologous hematopoietic \ncell transplant\na.Moderna model: “≥ 1 chronic medical condition” included asthma, COPD, coronary artery disease, congestive heart failure, chro nic kidney disease, chronic liver disease, diabetes mellitus, , \nand severe obesity.\nb.Pfizer model: “≥ 1 chronic or immunocompromising medical condition” included cardiovascular disease, hematologic disease, hep atic disease, metabolic disorders, pulmonary disease, renal \ndisease, severe obesity (BMI ≥40 kg/m2), and immunocompromising conditions.\nc.University of Michigan -CDC model: “≥ 1 chronic medical condition” included asthma, COPD, coronary artery disease, chronic kidney  disease, diabetes mellitus, and severe obesity (BMI ≥40 \nkg/m2). \n7UM-CDC GSK\nIncidence of RSV outpatient illness \n(per 100,000 persons per year)2,940 for adults 50 -59 years with cardiopulmonary \ndisease (e.g., COPD) a\n1,722  for adults 50 -59 years with other chronic \ncondition (e.g., diabetes mellitus) a2,926  \nfor adults 50 -59 years with COPD a\nIncidence of RSV hospitalization\n(per 100,000 persons per year)106 for adults 50 -59 years with ≥1 chronic \ncondition b \n169 for adults 50 -59 years with COPD, specifically b311\nfor adults 50 -59 years with COPD c\nMedical costs per RSV hospitalization\n$40,439 ($32,352 –$48,527)d $30,774\n(range +/ - 20% )e\nMedical costs per RSV ED visit and \nper RSV Outpatient visit$5,235 ($4,188 –$6,282)d\n$586 ($469 –$704)d$884  (range +/ - 20%)f\n$256 (range +/ - 20%)f\na.Adapted from Belongia  et al. Open Forum Infect Dis (2022). https://pubmed.ncbi.nlm.nih.gov/30619907/ . Adjusted upward by a factor of 1.5 for diagnostic test sensitivity in detecting RSV \ninfection (McLaughlin et al. [2022]) https://pubmed.ncbi.nlm.nih.gov/35873302/  \nb.CDC unpublished data, updates to analysis presented to ACIP (Woodruff, February 2024: https://www.cdc.gov/acip/downloads/slides -2024 -02-28-29/03 -RSV-Adults -Woodruff -508.pdf ).\nc.Adapted from Branche et al. (2022), https://pubmed.ncbi.nlm.nih.gov/34244735/  across Rochester and New York City sites adjusted by a factor of 1.5 for diagnostic test sensitivity in \ndetecting RSV infection (McLaughlin et al. [2022]) https://pubmed.ncbi.nlm.nih.gov/35873302/  \nd.For the general population, adjusted according to results for adults with and without chronic conditions. Averin  et al. (2024) https://pubmed.ncbi.nlm.nih.gov/38486815/\ne.CMS Medicare Inpatient Hospitals - by Geography and Service (CMS, 202 4); (DRG Average Payments from 2022 dataset); Falsey  et al. (2005) https://pubmed.ncbi.nlm.nih.gov/15858184/   \nf.CMS.gov Hospital Outpatient Prospective Payment (CMS, 2024). Average of CPT 99283 and 99284.  Added is the physician fee from  CMS.gov Physician Fee Lookup Tool (CMS, 2024). Average \nof CPT 99283 and 99284. https://www.cms.gov/medicare/payment/prospective -payment -systems/hospital -outpatient/regulations -notices/cms -1786 -fc UM-CDC and GSK models:  Incidence and medical \ncosts of RSV hospitalization and outpatient care\n8UM-CDC Moderna\nIncidence of RSV outpatient illness\n(per 100,000 persons per year) 1,722  for adults 50 -59 years with  ≥1 chronic \nconditiona2,322  for adults 50 -59 years with ≥1 \nconditions and \n964 for adults 50 -59 years, \nwithout chronic conditionsb\nIncidence of RSV hospitalization\n(per 100,000 persons per year)106 for adults 50 -59 years with ≥ 1 chronic \ncondition c 217.9  for adults 50 -59 years with ≥1 \nconditions b\nMedical costs per RSV hospitalization$40,439 \n($32,352 – $48,527) e $11,876 \n($8,407 - $47,512)f\nMedical costs per RSV ED visit and \nper RSV Outpatient visit$5,235 ($4,188 – $6,282)  e\n$586 ($469 – $704) e$4,399 ( no range ) d, g\n$2,273 ( no range ) f\na. Adapted from Belongia  et al. Open Forum Infect Dis (2022). https://pubmed.ncbi.nlm.nih.gov/30619907/ . Adjusted upward by a factor of 1.5 for diagnostic test sensitivity in detecting RSV infection \n(McLaughlin et al. [2022]) https://pubmed.ncbi.nlm.nih.gov/35873302/  \nb. Adjusted by 1.5x for PCR test sensitivity. Adapted from McLaughlin et al. Open Forum Infect Dis (2022), https://pubmed.ncbi.nlm.nih.gov/30619907/  and Weycker  (2024), \nhttps://pubmed.ncbi.nlm.nih.gov/38236516/  using methods applied in Averin  (2024), https://pubmed.ncbi.nlm.nih.gov/38486815/   \nc. CDC unpublished data, updates to analysis presented to ACIP (Woodruff, February 2024: https://www.cdc.gov/acip/downloads/slides -2024 -02-28-29/03 -RSV-Adults -Woodruff -508.pdf ).\nd. Averin  et al. (2024) Supplemental Table 3 https://pubmed.ncbi.nlm.nih.gov/38486815/\ne. For the general population, adjusted according to results for adults with and without chronic conditions. Averin  et al. (2024) https://pubmed.ncbi.nlm.nih.gov/38486815/\nf. Wyffels  et al. (2020), https://pubmed.ncbi.nlm.nih.gov/32026380/  (Moderna’s technical report provides inpatient cost ranges based on assumptions and supported by other studies)\ng. Merative  MarketScan  Commercial Claims and Encounters (CCAE) and Medicare Supplemental Coordination of Benefits (MDCR) Databases (2016 -2019)UM-CDC and Moderna  models:  Incidence and \nmedical costs of RSV hospitalization and outpatient care\n9UM-CDC Pfizer\nIncidence of RSV outpatient illness \n(per 100,000 persons per year)1,722  for adults 50 -59 years with ≥1 chronic \nmedical condition (e.g., diabetes mellitus) a3,158 \nfor adults 50 -59 years with ≥1 condition b\nIncidence of RSV hospitalization\n(per 100,000 persons per year)106 for adults 50 -59 years with ≥ 1 chronic \ncondition c 367\nfor adults 50 -59 years with ≥1 condition b\nMedical costs per RSV hospitalization$40,439 \n($32,352 – $48,527) d $40,361\n(no range reported)e\nMedical costs per RSV ED visit and \nper RSV Outpatient visit$5,235 ($4,188 – $6,282)  d\n$586 ($469 – $704) d$6,168  ( no range reported ) d, e\n$933 ( no range reported ) d, e\na.Adapted from Belongia  et al. Open Forum Infect Dis (2022). https://pubmed.ncbi.nlm.nih.gov/30619907/ . Adjusted upward by a factor of 1.5 for diagnostic test sensitivity in detecting RSV \ninfection (McLaughlin et al. [2022]) https://pubmed.ncbi.nlm.nih.gov/35873302/  \nb.Adapted from McLaughlin et al. (2022), https://pubmed.ncbi.nlm.nih.gov/35873302/ ; Weycker  et al. (2024), https://pubmed.ncbi.nlm.nih.gov/38236516/ ; Ramirez et al. (2023), \nhttps://pubmed.ncbi.nlm.nih.gov/37148463/ ; Onwuchekwa et al. (2023), https://pubmed.ncbi.nlm.nih.gov/36661222/ . Age and risk group is 50 -64 years  with selected chronic or \nimmunocompromising medical conditions.\nc.CDC unpublished data, updates to analysis presented to ACIP (Woodruff, February 2024: https://www.cdc.gov/acip/downloads/slides -2024 -02-28-29/03 -RSV-Adults -Woodruff -508.pdf ).\nd.For the general population, adjusted according to results for adults with and without chronic conditions. Averin  et al. (2024) https://pubmed.ncbi.nlm.nih.gov/38486815/\ne.Averin  et al (2024) , https://doi.org/10.1093/ofid/ofae097  .UM-CDC and Pfizer  models:  Incidence and \nmedical costs of RSV hospitalization and outpatient care\nGSK, Moderna , Pfizer  and UM-CDC models: \nMortality, indirect costs and quality -adjusted life -years \n10GSK Moderna Pfizer  UM-CDC\nMortality\n(case fatality \nratio, CFR)7.0%  CFR among COPD \nhospitalized for RSV -LRTD4.3%  CFR among hospitalized 4.7%  CFR among hospitalized \n50-64y CMC+6.4 deaths per 100 RSV \nhospitalizations, inclusive of \ndeaths among non -\nhospitalized persons\nIndirect costs\n(productivity \nlosses)Premature death \n      Market: \n50-54 years: $871,542 \n55-59 years: $601,091\nNonmarket: \n50-54 years: $691,270\n55-59 years: $621,604\nDays of work lost\nInpatient care: 15.18 \nED/Outpatient care: 4.30\nNo treatment: 0.50Premature death \nNot included in their analyses\nDays of work lost\nInpatient care: 7.53\nED care: 3.30\nOutpatient care: 2.30\nPresenteeism: 1 day all cases\nCaregiver: 0.75x patient’s timePremature death \n50-59 years with CMC+: \n$333,915 \nDays of work lost\nInpatient care: 10\nED/Outpatient care: 5\nCaregiver: 0.50x patient’s timePremature death \nAge-specific annual mortality \nand life expectancy from life \ntablesa multiplied by market \nand non -market foregone \nincome and discounted at 3% \nper year\nDays of work lost\nInpatient care:  8\nED/Outpatient care: 2.50\nQALY LossRSV-URTD 0.0133\nRSV-LRTD  0.0178  ED/Outpatient 0.0185\n       Inpatient    0.0193\n  No treatment 0.0093ED/Outpatient 0.0054\n           Inpatient 0.0167Outpatient  0.0185\nInpatient  0.0193\na. Vital Statistics Reports. National Vital Statistics Reports Vol 71, No 1, August 8, 2022. United States Life Tables, 2020. Pu b. online 2022. Accessed March 7, 2025. https://www.cdc.gov/nchs/products/index.htm  \nAbbreviations : COPD= chronic obstructive pulmonary disease, LRTD= lower respiratory tract disease, CFR= case fatality ratio, ED= Emergency d epartment, CMC+= selected chronic or immunocompromising \nmedical conditions, QALY= quality -adjusted life -year\n42 48 54 60\nGSK (RSVPreF3) and UM-CDC (subunit): Modeled vaccine \neffectiveness and duration of protection per outcome\n11\nThe pink -shaded area denotes a higher level of uncertainty of the waning assumption\na. Three -year projected effectiveness against ED and hospitalization based on a meta -analysis of real -world vaccine effectiveness s tudies. Base case truncated at 36 \nmonths based on available clinical follow -up extending only through three RSV seasons for a subunit vaccineGSKSource : La EM, et al.. \nHum Vaccin  \nImmunother . 2024 \nDec \n31;20(1):2432745. \nhttps://doi.org/10.1\n080/21645515.2024.\n2432745  \nLRTD= Lower \nrespiratory tract \ndisease, ARI = acute \nrespiratory infectionSource : UM -CDC \nis based on \nHutton et al. \nACIP \npresentation \n(Apr 2025) and \non an \nunpublished \nmanuscriptUM-CDCa\n42 48 54 60\n84.6%\n65.1%72.0%\n47.0%____  \nOutpatient visit  \n(PO/HO)\n____  \nHospitalization \n(including ICU & \ndeath) and EDPfizerb\n12Pfizer (RSVpreF ) and UM-CDC (subunit): Modeled vaccine \neffectiveness and duration of protection per outcome\nUM-CDCa\nThe pink -shaded area denotes a higher level of uncertainty of the waning assumption beyond available phase 3 data\na.UM-CDC: Three -year projected effectiveness against ED and hospitalization based on a meta -analysis of real -world vaccine effecti veness studies. Base case truncated at 36 \nmonths based on available clinical follow -up extending only through three RSV seasons for a subunit vaccine\nb.Pfizer model: Base -case vaccine effectiveness against RSV -Hospital and RSV -ED corresponding to the solid blue line was applied. The dotted blue line reflects vaccine \neffectiveness against RSV -Hospital and RSV -ED if the waning pattern would persist.Source : Pfizer \nTechnical report \nand Slides \nsubmitted to \nCDC  (2024 and \nJanuary 2025)\nICU = Intensive \ncare unit, ED= \nEmergency \ndepartment, \nPO= physician \noffice, HO = \nhospital \noutpatientSource : UM -\nCDC is based on \nHutton et al. \nACIP \npresentation \n(Apr 2025) and \non an \nunpublished \nmanuscript\nModerna  and UM-CDC: Modeled vaccine \neffectiveness and duration of protection per outcome\n13UM-CDCa (two-year timeframe: solid lines )\nScenario:  3-year timeframe linear decay, 0% at 36 months: dotted lines \nThe pink -shaded areas denote a higher level of uncertainty of the waning assumption beyond available phase 3 data\na.UM-CDC base case truncated at 24 months based on available clinical follow -up extending only through a median of <24 months per participant\n   Source: for Moderna, Moderna's technical report (2025) and for UM -CDC, Hutton et al., ACIP Presentation (Apr 2025) Moderna  (three -year timeframe ) \nARD = Acute respiratory disease\nLRTD =Lower respiratory tract disease\nED = Emergency department86.7%\n83.7%\n68.4%\n____  Vaccine effectiveness for RSV Hospitalization & ED = VE LRTD ≥2 symptoms\n____ Vaccine effectiveness for RSV Outpatient= VE medically attended ARD\n\na.GSK estimated cost -saving values for COPD (base -case) and for each selected individual condition: heart failure, CAD, asthma and di abetes.  \nb.In the 3 -year timeframe  for a generic protein subunit vaccine effectiveness , UM-CDC estimated a societal cost of $ 43,070/QALY saved  for adults with at least one \nchronic condition (COPD, asthma, CAD, CKD, severe obesity, or diabetes) vaccinated with subunit  RSV vaccine. For individual conditions, when vaccinating with a \ngeneric protein subunit RSV vaccine, ICERs ranged from cost -saving (CKD, COPD, BMI ≥40) to $ 57,441  (Diabetes) per QALY saved. When evaluating other specific \nconditions not included in “at least one” , $/QALY for adults aged 50 -59 years were also cost -saving (i.e., lung transplant, allogeneic hematopoietic cell transplant, and  \nautologous hematopoietic cell transplant, heart failure).\nAbbreviations : COPD= Chronic obstructive pulmonary disease, CAD=Coronary artery disease, CKD= Chronic kidney disease, ICER= Incremental co st-effectiveness ratio, \nBMI = Body mass index, QALY= quality -adjusted life -year Incremental cost -effectiveness:  \nGSK and UM-CDC\nPolicy question:  What is the incremental cost-effectiveness  of vaccinating adults aged 50 -59 years \noldat increased risk  of severe RSV illness relative  to “No vaccination”? \n14GSK UM-CDC\n$/QALY saved ( 3-year \ntimeframe )Cost -saving (COPD)a $44,203b\nFor a generic protein subunit RSV vaccine:\n•Cost -saving: CKD, COPD, BMI≥40\n•$9,889 (Asthma)\n•$13,177 (CAD)\n•$57,441 (Diabetes) \n$/QALY saved ( 5-year \ntimeframe )Cost -saving (COPD)a\n(base -case)Not included\na.Pfizer  model  estimated cost -saving values for selected high -risk conditions: COPD, CAD, CKD, diabetes mellitus, immune compromised an d severe immune compromised. \nBase -case used a 3.5 -year vaccine efficacy duration from Phase 3 clinical trials.\nb.In the 3 -year timeframe for a generic protein subunit vaccine effectiveness , UM -CDC estimated a societal cost of $ 43,070/QALY saved for adults with at least one chronic condition \n(COPD, asthma, CAD, CKD,  severe  obesity , or diabetes ) vaccinated with subunit RSV vaccine. For individual conditions, when vaccinating with a generic protein subunit RSV vaccine, ICERs \nranged from cost -saving (CKD, COPD, BMI>40) to $57,441  (Diabetes) per QALY saved. When evaluating other specific conditions not included in “at least one” , $/QALY for 50-59 years old \nwere also cost -saving (i.e., lung transplant, allogeneic hematopoietic cell transplant, autologous hematopoietic cell transplant , and heart failure).\nAbbreviations : COPD= Chronic obstructive pulmonary disease, CAD=Coronary artery disease, CKD= Chronic kidney disease, ICER= Incremental co st-effectiveness ratio, BMI = \nBody mass index, QALY= quality -adjusted life -year Incremental cost -effectiveness:\n Pfizer  and UM-CDC\nPolicy question:  What is the incremental cost-effectiveness  of vaccinating adults aged 50 -59 years \noldat increased risk  of severe RSV illness relative  to “No vaccination”? \n15Pfizera UM-CDCb\n$/QALY saved ( 3- to 3.5 -\nyear timeframe ) base -caseCost saving $41,754\nFor a generic protein subunit RSV vaccine:\n•Cost -saving: CKD, COPD, BMI≥40\n•$9,889 (Asthma)\n•$13,177 (CAD)\n•$57,441 (Diabetes) \n$/QALY saved ( 70 months \ntimeframe scenario )Cost Saving Not included\na.Moderna reported $/QALY of $40,493 (COPD), $64,289 (CLD), $$61,504 (CKD), $83,598 (Diabetes) and $65,125  (severe obesity, BMI≥  40.\nb.In the base case (2 -year timeframe), UM -CDC estimated a societal cost of $ 152,293/QALY saved for adults with at least one chronic condition (COPD, asthma, CAD, CKD, severe \nobesity, or diabetes). When evaluating other specific conditions not included in “at least one,”  $/QALY reported were cost -saving (i.e., lung transplant, allogeneic hematopoietic \ncell transplant, autologous hematopoietic cell transplant, and heart failure ).\nAbbreviations : CHF= Congestive heart failure, COPD= Chronic obstructive pulmonary disease, CLD= Chronic liver disease, CAD=Coronary artery  disease, CKD= Chronic kidney disease, \nICER= Incremental cost -effectiveness ratio, BMI = Body mass index, QALY= quality -adjusted life -year Incremental cost -effectiveness:\nModerna  and UM-CDC\nPolicy question:  What is the incremental cost-effectiveness  of vaccinating adults aged 50 -59 years \noldat increased risk  of severe RSV illness relative  to “No vaccination”? \n16Moderna UM-CDC\n$/QALY saved ( 2-year \ntimeframe )$75,862 $152,293 (Base case)b\nFor individual conditions costs ranged from \n$6,052 (CKD) to\n$174,454 (Diabetes) per QALY saved\n$/QALY saved ( 3-year \ntimeframe ) $65,125 (Base case)a\nFor individual conditions costs ranged \nfrom $10,889 (CHF and heart failure) to \n$95,606 (Asthma) per QALY saved$95,182\nFor individual conditions ranged from cost -\nsaving (CKD) to $114,315 (Diabetes) per \nQALY saved\nLimitations\n17•Factors not considered that may result in underestimating the cost -effectiveness of RSV \nvaccination\n•Impact of RSV on long -term prognosis of included higher risk conditions \n•Indirect effects of vaccination (i.e., protection against RSV transmission)\n•Quality -of-life impact on caregivers during RSV illness\n•Two models ( GSK, UM-CDC) do not include, and two models (Moderna, Pfizer ) partially include\n•Productivity impact (work time missed) on caregivers during RSV illness\n•Manufacturer models do not include  RSV-related medical costs incurred after discharge from an RSV -associated \nhospitalization or emergency department visit (i.e., stay in long -term care or rehabilitation facility)\n•Partially  include potential  vaccine -associated serious adverse events (SAEs) or Guillain Barre syndrome (GBS): Quality \nof life impact, resource utilization, and costs associated with SAEs, including GBS specifically for protein subunit RSV \nvaccines.\n•Duration of vaccine protection beyond clinical trial follow -up time ( beyond median 19 months, \nModerna ; mean 18 months , Pfizer ormedian 31 months ,GSK) is unknown  \n•All 4 models assumed non -zero declining  efficacy beyond trial time data\n•All 4 models assumed optimal timing of vaccination, in the late summer and early fall, prior to \nRSV season onset .\nConclusion\n18•Differences in key inputs and assumptions among GSK, Moderna , Pfizer  and UM-CDC models \nexplain differences in results:\n•Annual incidence of RSV hospitalization and outpatient disease\n•Initial vaccine efficacy/effectiveness and waning of protection assumptions\n•Medical cost per RSV hospitalization \n•Resulting ICERs for policy question also vary by vaccine type and risk condition\n•Vaccinating adults aged 50 -59 years old at increased risk of severe RSV disease  showed disperse \n$/QALY ratios\n•Assuming 3 years of vaccine protection: \n•Outcomes for PreF  combined subunit RSV vaccine ranged from societal cost-saving  (GSK and Pfizer models and \nfor all included high -risk conditions ) to $43,070  per QALY saved ( UM-CDC, though some high -risk conditions were \nreported to be cost -saving)\n•Outcomes for PreF  mRNA RSV vaccine ranged from $65,125 ( Moderna ) to $ 95,182 (UM-CDC) per QALY saved\n•Overall, vaccination would significantly reduce RSV disease burden in adults 50 -59 years at \nincreased risk of severe RSV disease.\n•Efficacy data from clinical trials from all vaccines as well as conservative assumptions about \nduration of protection support impact on disease reduction and health risks\nAcknowledgements \nFrom NCIRD/CDC\n•Michael Melgar\n•Amadea Britton\n•Andrew Leidner \n•Ruth Link -Gelles\n•Allison Ciesla\n•Meredith McMorrow\nAlso:\n•Adult RSV working group members\n19\n\nSelected references \n20Averin  A,  Atwood M, Sato R, et al.  Attributable Cost of Adult Respiratory Syncytial Virus Illness Beyond the Acute Phase, Open For um Infectious Diseases, Volume 11, Issue 3, March \n2024, ofae097, https://doi.org/10.1093/ofid/ofae097  \nBelongia  EA, King JP,  Kieke  BA, et al.  Clinical Features, Severity, and Incidence of RSV Illness During 12 Consecutive Seasons in a Community Cohort of Adults ≥60 Years Old, Open Forum \nInfectious Diseases, Volume 5, Issue 12, December 2018, ofy316, https://doi.org/10.1093/ofid/ofy316  \nBranche AR, Saiman L,  Walsh EE, et al.  Incidence of Respiratory Syncytial Virus Infection Among Hospitalized Adults, 2017 –2020 , Clinical Infectious Diseases, Volume 74, Issue 6, 15 \nMarch 2022, Pages 1004 –1011, https://doi.org/10.1093/cid/ciab595  \nFalsey  AR, Hennessey PA, Formica MA, Cox C, Walsh EE. Respiratory syncytial virus infection in elderly and high -risk adults. N Engl J Med. 2005 Apr 28;352(17):1749 -59. doi: \n10.1056/NEJMoa043951. PMID: 15858184. https://doi.org/10.1056/nejmoa043951  \nHavers FP, Whitaker M, Melgar M, et al. Burden of Respiratory Syncytial Virus -Associated Hospitalizations in US Adults, October 2016 to September 2023. JAMA Netw  Open. 2024 Nov \n4;7(11):e2444756. doi: 10.1001/jamanetworkopen.2024.44756. PMID: 39535791; PMCID: PMC11561688. https://doi.org/10.1001/jamanetworkopen.2024.44756    \nLa EM, Graham J, Singer D, et al. Cost -effectiveness of the adjuvanted RSVPreF3 vaccine among adults aged ≥60 years in the Unite d States. Hum Vaccin  Immunother . 2024 Dec \n31;20(1):2432745. https://doi.org/ 10.1080/21645515.2024.2432745     \nLopez E, Neuman T, Jacobson G, Levitt L. How Much More Than Medicare Do Private Insurers Pay? A Review of the Literature. Kai ser Family Foundation; 2020.  Website,  last visited  Feb \n18,2025 https://www.kff.org/medicare/issue -brief/how -much -more -than -medicare -do-private -insurers -pay-a-review -of-the-literature/  \nM McLaughlin JM, Khan F,  Begier  E, et al.  Rates of Medically Attended RSV Among US Adults: A Systematic Review and Meta -analysis, Open Forum Infectious Diseas es, Volume 9, Issue \n7, July 2022, ofac300, https://doi.org/10.1093/ofid/ofac300  \nNguyen -Van-Tam JS, O'Leary M, Martin ET, Heijnen  E, Callendret  B, Fleischhackl  R, Comeaux C, Tran TMP, Weber K. Burden of respiratory syncytial virus infection in older and high -risk \nadults: a systematic review and meta -analysis of the evidence from developed countries. Eur Respir Rev. 2022 Nov 15;31(166):220105. doi: 10.1183/16000617.0105 -2022. PMID: \n36384703; PMCID: PMC9724807. https://doi.org/10.1183/16000617.0105 -2022  \nOnwuchekwa C, Moreo LM, Menon S, et al. Underascertainment  of Respiratory Syncytial Virus Infection in Adults Due to Diagnostic Testing Limitations: A Systematic Literature Review \nand Meta -analysis. J Infect Dis. 2023;228(2):173 -184 https://doi.org/10.1093/infdis/jiad012  \nRamirez J, Carrico R, Wilde A, et al. Diagnosis of Respiratory Syncytial Virus in Adults Substantially Increases When Adding Sputum, Saliva, and Serology Testing to Nasopharyngeal Swab \nRT PCR. Infect Dis Ther . 2023;12(6):1593 -1603 https://doi.org/10.1007/s40121 -023-00805 -1 \nWeycker  D, Averin  A, Houde  L, et al. 2207. Rates of Lower Respiratory Tract Infections Among US Adults Aged ≥18 Years With and Without Chronic Medical C onditions. Open Forum \nInfectious Diseases. 2022;9(Supplement_2)  https://doi.org/10.1093/ofid/ofac492.1826  \nWyffels , V., Kariburyo , F., Gavart , S. et al. A Real -World Analysis of Patient Characteristics and Predictors of Hospitalization Among US Medicare Beneficiaries w ith Respiratory Syncytial \nVirus Infection. Adv Ther  37, 1203 –1217 (2020). https://doi.org/10.1007/s12325 -020-01230 -3 \nEnd of Summary\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    cdc.gov\nFollow us on X (Twitter) @CDCgov & @CDCEnvironment\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position o f the U. \nS. Centers for Disease Control and Prevention.", "summary": "Economics of Respiratory Syncytial Virus  Vaccination in Adults aged 50 -59 years  at Increased Risk of Severe RSV Disease SUMMARY COMPARING MODELS FROM: GSK,Moderna ,Pfizer AND University of Michigan -CDC Ismael R. Ortega -Sanchez, PhD NCIRD/CDC ACIP Meeting, April 16, 2025 1Disclaimer : The findings and conclusions in this report are those of the authors and do not necessarily represent the views of  the Centers for Disease Control and Prevention.  Conflicts of interest •GSK model : David…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/05-Ortega-Sanchez-Adult-RSV-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 21}
{"title": "06 Melgar Surie adult rsv 508", "content": "Evidence to Recommendations Framework (EtR):\nRSV Vaccination in Adults Aged 50 –59 years\nAmadea Britton, MD, Co -Lead Adult RSV Vaccine Work Group\nMichael Melgar, MD, Co -Lead Adult RSV Vaccine Work Group\nDiya Surie, MD, Co -Lead Adult RSV Vaccine Work Group\nCoronavirus and Other Respiratory Viruses Division (CORVD)\nAdvisory Committee on Immunization Practices (ACIP)\nApril 16, 2025National Center for Immunization and Respiratory Diseases\n2•Should adults aged 50 –59 years at increased risk of severe RSV disease \nbe recommended to receive a single dose of RSV vaccination?Policy questions\n3We plan to consider adults aged 18 –49 years at increased \nrisk of severe RSV disease at the June 2025 meeting. \n4•ACIP Evidence to Recommendations Framework (cdc.gov)Evidence to Recommendations ( EtR) framework\nEtR Domain Question(s)\nPublic Health Problem ▪Is the problem of public health importance?\nBenefits and Harms ▪How substantial are the desirable anticipated effects?\n▪How substantial are the undesirable anticipated effects?\n▪Do the desirable effects outweigh the undesirable effects?\nValues ▪Does the target population feel the desirable effects are large relative \nto the undesirable effects?\n▪Is there important uncertainty about, or variability in, how much \npeople value the main outcomes?\nAcceptability ▪Is the intervention acceptable to key stakeholders?\nFeasibility ▪Is the intervention feasible to implement?\nResource Use ▪Is the intervention a reasonable and efficient allocation of resources?\nEquity ▪What would be the impact of the intervention on health equity?\nEtRDomain: Public Health Problem\nIs the problem of public health importance among adults aged 50 -59 years at \nincreased risk of severe RSV disease?\n6•Population -based rates of RSV disease among adults aged 50 –59 years are \nlower than those among older adultsWhat do we know about RSV epidemiology in adults aged \n50–59 years?\n7Estimated annual RSV -associated hospitalization rates per 100,000 adults* \naged ≥18 years by age group and year, RSV -NET, 2016 –17 to 2019 –20 and \n2022 –23\n0100200300400500600700\n18–49 50–54 55–59 60–64 65–69 70–74 ≥75 Annual RSV -associated \nhospitalizations per 100,000 \npopulation \nAge group, years2016 –17\n2017 –18\n2018 –19\n2019 –20\n2022-23Surveillance \nseason:\nHavers FP, et al. Burden of Respiratory Syncytial Virus –Associated Hospitalizations in US Adults, October 2016 to September 2023 . JAMA Netw  Open. 2024;7(11):e2444756. https://pmc.ncbi.nlm.nih.gov/articles/PMC11561688/  \nHospitalization rates were adjusted for under -detection of RSV infection due to testing practices and diagnostic test sensitivit y. Season is defined as October to April for 2016 to 2017 through 2019 to 2020 and as October to \nSeptember for 2022 to 2023. Error bars represent 95% CIs.\n*Estimated rates exclude recorded hospitalizations among pregnant women.Risk-based recommendationAge-based recommendation\n8Estimated  annual number  of \nRSV-associated \nhospitalizations * among \nadults aged ≥18 years by age \ngroup and year, RSV -NET, \n2016 –17 to 2019 –20, 2022 –23\n0 20,000 40,000 60,000 80,000 100,000≥80 75–7970–7465–6960–6455–5950–5418–49\nAnnual RSV -associated hospitalizationsAge \ngroup, \nyears2016 –17 2017 –18 2018 –19 2019 –20 2022 –23\nHavers FP , et al. Burden of Respiratory Syncytial Virus -Associated \nHospitalizations in US Adults, October 2016 to September 2023. JAMA \nNetw  Open. 2024 Nov 4;7(11):e2444756. \nhttps://pubmed.ncbi.nlm.nih.gov/39535791/  \n*Estimated hospitalizations exclude recorded hospitalizations among \npregnant women.Estimated  15,000 –20,000 \nannual RSV -associated \nhospitalizations  in \nU.S. adults aged 50–59 yearsSurveillance \nseason:\n9•Population -based rates of RSV disease among adults aged 50 –59 years are \nlower than those among older adults\n•However, we know that some younger adults are at increased risk of RSV \nhospitalization, even if the risk in the general population is lowWhat do we know about RSV epidemiology in adults aged \n50–59 years?\n10Top 10 most common underlying medical conditions among \nadults aged ≥50 years hospitalized with RSV are similar by age\nMajor medical condition categories \namong persons aged 50–59 years \nhospitalized with RSVWeighted \n%\nCardiovascular disease 46.3\nDiabetes mellitus 37.0\nAsthma 29.7\nCOPD or chronic bronchitis 26.5\nImmunocompromised condition 25.5\nSevere obesity (BMI ≥40 kg/m2) 21.3\nChronic kidney disease 19.8\nNeurologic disorder 19.4\nGastrointestinal, liver, or pancreatic \ndisease9.8\nBlood disorder 4.5Major medical condition categories \namong persons aged ≥60 years \nhospitalized with RSVWeighted \n%\nCardiovascular disease 66.7\nDiabetes mellitus 36.9\nCOPD or chronic bronchitis 35.0\nChronic kidney disease 29.1\nNeurologic disorder 26.5\nImmunocompromised condition 18.5\nAsthma 18.1\nSevere obesity (BMI ≥40 kg/m2) 10.7\nGastrointestinal, liver, or pancreatic \ndisease6.5\nRheumatologic disease 4.2\nBMI: body mass index; COPD: chronic obstructive pulmonary disease\nUnpublished RSV -NET data, 2015 –2016 to 2017 –2018, 2022 –2023, and 2023 –2024\nCategories are not mutually exclusive; individual patients may have underlying conditions in more than one category Slide credit: Dr. Monica Patton\n11Unpublished data. Update on analysis from Woodruff et al. First presented to ACIP in February 2024: https://www.cdc.gov/acip/downloads/slides -2024 -02-28-29/03 -RSV-Adults -Woodruff -508.pdf  \nBMI: Body Mass Index (kg/m2), COPD: Chronic Obstructive Pulmonary Disease. Data are preliminary and unpublished. Current smoking is defined as smoking c igarettes every day or some days at the time of survey response. \nAdjusted rate ratios and 95% confidence intervals are derived from Poisson regression using Monte Carlo simulation methods an d adjust for age, sex and race and ethnicity group. Error bars represent 95% confidence intervals.Adjusted Rate Ratios for RSV -Associated Hospitalization by Chronic \nCondition among Community -Dwelling Adults Aged ≥50 Years\n6.5\n4.63.73.12.42.0 1.91.51.3\n0.11.010.0100.0\nChronic\nKidney\nDiseaseCOPD Severe \nobesity\n(BMI ≥40)Asthma Coronary\nArtery\nDiseaseDiabetes\nmellitusCurrent\nsmokerStroke Obesity\n(BMI 30-39)Adjusted rate ratio\n12aRR (95% CI)1\nNumber of chronic conditions2\n0 ref\n1 2.1 (1.4, 3.2)\n≥2 7.3 (5.0, 10.6)\nAge group, years\n50–59 ref\n60–74 1.9 (1.3, 2.7)\n≥75 6.0 (4.2, 8.6)\nRace or ethnicity group\nWhite, non -Hispanic ref\nBlack, non -Hispanic 1.1 (0.8, 1.5)\nOther race or Hispanic ethnicity 1.7 (1.3, 2.5)\nSex\nMale Ref\nFemale 1.3 (1.0, 1.6)\n1 Adjusted rate ratios ( aRR) and 95% confidence intervals (CI) were estimated using \nPoisson regression and Monte Carlo simulation. Adjusted for all covariates in table.\n2 Includes history of asthma, chronic kidney disease, chronic obstructive pulmonary \ndisease, coronary artery disease, current smoker, diabetes, stroke, obesity (body mass \nindex [BMI] 30 –39 kg/m2) or severe obesity (BMI ≥40 kg/m2)Among community -dwelling \nadults aged ≥50 years, a \nhistory of ≥2 chronic \nconditions  and age ≥75 years \nwere the strongest \nindependent  risk factors for \nRSV-associated hospitalization.\nUnpublished data. Update on analysis from Woodruff et al. First presented to ACIP in February 2024 : https://www.cdc.gov/acip/downloads/slides -2024 -02-28-29/03 -RSV-Adults -Woodruff -508.pdf  \n13RSV-associated hospitalization rates among community -dwelling adults \naged ≥50 years with chronic medical conditions, 2017 –2018 season\nBMI: Body Mass Index (kg/m2), COPD: Chronic Obstructive Pulmonary Disease. Data are preliminary and unpublished. Rates of laboratory -confirmed RSV -associat ed hospitalization account for under -detection of RSV infection \namong hospitalized adults and sensitivity of diagnostic tests. Poisson regression using Monte Carlo simulation estimated rate s and 95% confidence intervals (represented by error bars). Rates for community -dwelling adults \nexclude residents of nursing homes and long -term care facilities and are not adjusted for sex or race and ethnicity group.0200400600\n50–59\n60–74\n≥75\n50–59\n60–74\n≥75\n50–59\n60–74\n≥75\n50–59\n60–74\n≥75\n50–59\n60–74\n≥75\n50–59\n60–74\n≥75\n50–59\n60–74\n≥75\n50–59\n60–74\n≥75\n50–59\n60–74\n≥75\n50–59\n60–74\n≥75\nNone of\nThese\nConditionsChronic\nKidney\nDiseaseCOPD Severe \nobesity\n(BMI ≥40)Asthma Coronary\nArtery\nDiseaseDiabetes\nmellitusStroke Obesity\n(BMI 30 –\n39)Current\nsmokerRSV-associated hospitalization rate \n(per 100,000)\nCommunity -dwelling adults \nwith none of these conditionsCommunity -dwelling adults \nwith each condition\n////////\n//////////////////\n14RSV-associated hospitalization rates among community -dwelling adults \naged ≥50 years with chronic medical conditions, 2017 –2018 season\nBMI: Body Mass Index (kg/m2), COPD: Chronic Obstructive Pulmonary Disease. Data are preliminary and unpublished. Rates of laboratory -confirmed RSV -associat ed hospitalization account for under -detection of RSV \ninfection among hospitalized adults and sensitivity of diagnostic tests. Poisson regression using Monte Carlo simulation esti mated rates and 95% confidence intervals (represented by error bars). Rates for community -\ndwelling adults exclude residents of nursing homes and long -term care facilities and are not adjusted for sex or race and ethnic ity group.0200400600\n50–59\n60–74\n≥75\n50–59\n60–74\n≥75\n50–59\n60–74\n≥75\n50–59\n60–74\n≥75\n50–59\n60–74\n≥75\n50–59\n60–74\n≥75\n50–59\n60–74\n≥75\n50–59\n60–74\n≥75\n50–59\n60–74\n≥75\n50–59\n60–74\n≥75\nNone of\nThese\nConditionsChronic\nKidney\nDiseaseCOPD Severe \nobesity\n(BMI ≥40)Asthma Coronary\nArtery\nDiseaseDiabetes\nmellitusStroke Obesity\n(BMI 30 –\n39)Current\nsmokerRSV-associated hospitalization rate \n(per 100,000)\nCommunity -dwelling adults \nwith none of these conditionsCommunity -dwelling adults \nwith each condition\n////////\n//////////////////\n15What do we know about conditions and risk factors not \nincluded in the RSV -NET analysis?\n1. Kujawski  SA, et al. Rates of respiratory syncytial virus (RSV) -associated hospitalization among adults with congestive heart failure -United States, 2015 -2017. PLoS  One. 2022 Mar 9;17(3):e0264890. \nhttps://pubmed.ncbi.nlm.nih.gov/35263382/  \n2. Ison MG, Hirsch HH. Community -Acquired Respiratory Viruses in Transplant Patients: Diversity, Impact, Unmet Clinical Needs. Clin  Microbiol  Rev. 2019 Sep 11;32(4):e00042 -19. https://pubmed.ncbi.nlm.nih.gov/31511250/  \n3. Manuel O, Estabrook M; American Society of Transplantation Infectious Diseases Community of Practice. RNA respiratory viral i nfections in solid organ transplant recipients: Guidelines from the American Society of \nTransplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e13511 https://pubmed.ncbi.nlm.nih.gov/30817023/  \n4. Waghmare A, et al. Supplemental Oxygen -Free Days in Hematopoietic Cell Transplant Recipients With Respiratory Syncytial Virus. J  Infect Dis. 2017 Dec 5;216(10):1235 -1244. https://pubmed.ncbi.nlm.nih.gov/28961971/  \n5. Martino R, et al. Prospective study of the incidence, clinical features, and outcome of symptomatic upper and lower respirato ry tract infections by respiratory viruses in adult recipients of hematopoietic stem cell transplants for \nhematologic malignancies. Biol Blood Marrow Transplant. 2005 Oct;11(10):781 -96. https://pubmed.ncbi.nlm.nih.gov/16182179/  \n6. Sheshadri  A, et al. Pulmonary Impairment after Respiratory Viral Infections Is Associated with High Mortality in Allogeneic Hematopoiet ic Cell Transplant Recipients. Biol Blood Marrow Transplant. 2019 Apr;25(4):800 -809. \nhttps://pubmed.ncbi.nlm.nih.gov/30521974/  \n7. Testaert  H, et al. Incidence, management and outcome of respiratory syncytial virus infection in adult lung transplant recipients: a 9 -year retrospective multicentre  study. Clin Microbiol  Infect. 2021 Jun;27(6):897 -903. \nhttps://pubmed.ncbi.nlm.nih.gov/32827713/  ▪ Other medical conditions associated with increased risk of severe RSV disease\n–Heart failure\n•As many as 28%  of adults hospitalized with RSV infection have chronic heart failure1\n•Among adults <65 years, hospitalization rates are >14x  higher in those with versus without \nheart failure1\n–Immune compromise\n•Severe RSV disease and high RSV -associated mortality ( >20% ), especially among hematopoietic \ncell transplant and lung transplant recipients2–4\n•RSV may account for 20 –25% of symptomatic viral respiratory illness after hematopoietic cell \ntransplant5 and is associated with pulmonary impairment and mortality.6\n•RSV infection is associated with increased risk of allograft dysfunction after lung transplant7\n16•Population -based rates of RSV disease among adults aged 50 –59 years are \nlower than those among older adults\n•However, we know that some younger adults are at increased risk of RSV \nhospitalization, even if the risk in the general population is low\n•Adults aged 50 –59 years who are hospitalized with RSV have similar \nunderlying conditions as those in hospitalized adults ≥60 years, but more \noften have asthma, immune compromise, and severe obesity\n•Adults aged 50 –59 years with certain chronic conditions experience RSV \nhospitalization rates similar to those in adults ≥75 years in whom age is the \nonly identified risk factor (who are recommended to receive RSV vaccination)\n•Adults with heart failure and immune compromise more often experience \nsevere outcomes from RSV infectionPublic health problem: Evidence in adults aged 50 –59 years\n17Prevalence of ≥1 chronic medical condition among adults aged 50-59 years is at least 31%  using a narrow \ndefinition of chronic medical conditions* and may be as high as 43% when using a broad definition** \nNational Health and Nutrition Examination Survey (NHANES), 2015 –2018.\nSOURCE: National Center for Health Statistics (NCHS), National Health and Nutrition Examination Survey (NHANES), 2015 –2018. All estimates are crude estimates with no age adjustment and age is age at interview. Error bars represent Korn and Graubard  95% confidence intervals. NHANES is representative of the civilian, non -institutionalized U.S. population. For \n“narrow” definition: Severe obesity was defined as BMI ≥40 kg/m2. Diabetes with complication was defined as 1) having diabetes: self -reported diabetes, fasting plasma glucose ≥126 mg/dL, or he moglobin A1c ≥6.5%, AND 2) having one of the following complications of diabetes assessed within the survey: serious heart di sease as defined below, chronic kidney disease \n(stage 3, 4, or 5) defined as estimated glomerular filtration rate (eGFR) ˂60 (stages 3 –5) further defined below, or having self -reported diabetes and having a doctor previously told them that diabetes affected their eyes or that they have retinopathy. O ther complications of diabetes are not included in this definition. Serious heart disease was defined based on self -report as \ndiagnosed congestive heart failure, coronary heart disease, angina, or heart attack, or angina grades 1 or 2 determined by th e Rose Angina Questionnaire. Asthma was defined as self -reporting ever being diagnosed with asthma and still having asthma. Chronic  kidney disease was defined as estimated glomerular filtration rate (eGFR) ˂30 (stages 4 –5), and using a forward \nequation for adjustment of creatinine because of methods changes. eGFR calculated using the 2021 CKD -EPI creatinine equation (ht tps://www.nejm.org/doi/10.1056/NEJMoa2102953). Urine albumin is not included in this definition. Chronic obstructive pulmonar y disease (COPD) was defined as self -reported diagnosed COPD, emphysema, or current chronic bronchitis. Liver \ncondition was defined as self -reporting ever being diagnosed with any kind of liver condition and still having any kind of liver  condition. Having at least one of the above conditions for the narrow definition was defined based on the seven (7) condition s listed. For “broad” definition: conditions were defined identically except diabetes was defined as self -reported diabetes, \nfasting plasma glucose ≥126 mg/dL, or hemoglobin A1c ≥6.5% without complication; chronic kidney disease was defined as estima ted glomerular filtration rate (eGFR) ˂60 (stages 3,4, or 5); and cancer or malignancy in past 2 years was added. This was define d as self -reporting having \"ever been told by a doctor or other health professional that you had cancer or a \nmalignancy of any kind\" and reporting age at diagnosis in years as being within 2 years of current age in years. As participa nt age and age at diagnosis for cancer or malignancy are top -coded for ages 80 years and above, those who are aged 80 years and abo ve and report having diagnosis at age 78 years or above are coded as having cancer or malignancy in the past 2 years; \nthis results in an inflated estimate. Of those with any history of cancer or malignancy ages 50 –79 years, 18.6% had a diagnosis within the past 2 years. Of those with any history of cancer or malignancy ages 80 years and above, 36.0% had a diagnosis at ≥ age 78 years. Having at least one of the above conditions for the broad definition was defined based on the eight (8) \nconditions listed. Among the fasting sample, ~94% had complete data for all reported medical conditions, ~6% were missing dat a for one (1) medical condition, <1% were missing data for two (2) medical conditions, and none were missing data for three (3) or more medical conditions. Estimates of having ≥1 condition are weighted using fasting sample weight.  *Narrow definition , at least one of:\n•Serious heart disease\n•Diabetes with complication\n•Chronic obstructive pulmonary disease\n•Asthma\n•Severe obesity (BMI ≥40 kg/m2)\n•Liver condition\n•Chronic kidney disease, stage 4 or 5\n**Broad definition , as above, OR:\n•Diabetes with or without  complication\n•Chronic kidney disease, stage 3, 4, or 5\n•Cancer or malignancy in past 2 years\nBMI: body mass index313945 435771\n0102030405060708090100\n50–59 years 60–74 years 75 years and olderPrevalence of at least one chronic \nmedical condition (%)\n18•Is RSV of public health importance among adults aged 50–59 \nyears at increased risk of severe RSV disease? Public Health Problem: Work Group interpretation\nNoProbably \nNoProbably \nYesYes VariesDon’t \nknow\nEtR Domain: Benefits and Harms\nAmong adults aged 50 -59 years at increased risk of severe RSV disease:\n•How substantial are the desirable anticipated effects of RSV vaccination?\n•How substantial are the undesirable anticipated effects of RSV vaccination?\n•Do the desirable effects outweigh the undesirable effects?\n20GRADE Framework: PICO Question\nPopulation Adults aged 50 –59 years at increased risk of severe RSV \ndisease\nIntervention RSV Vaccine:\nGSK Arexvy (1 dose IM) or Pfizer Abrysvo (1 dose IM) or \nModerna mResvia (1 dose IM)\nComparison No RSV vaccine\nOutcomes ▪Medically attended RSV lower respiratory tract disease (LRTD)\n▪Hospitalization for RSV respiratory illness\n▪Death due to RSV respiratory illness\n▪Serious Adverse Events (SAEs)\n▪Inflammatory neurologic events (e.g., Guillain -Barré syndrome)\nIM: intramuscular\n21•Protein subunit vaccines : GSK’s Arexvy , Pfizer’s Abrysvo\n•mRNA vaccine : Moderna’s mResvia  (not currently licensed for use in adults \naged <60 years)\n•Policy question is not product -specific, so additional RSV vaccines eventually \nlicensed in adults aged 50 -59 years at increased risk of severe RSV disease \nwould be included in an existing recommendation\n•All three vaccines are based on the same RSV antigen: F protein, stabilized in \nprefusion conformation ( preF )\n•Where relevant, we will show product -specific considerations outside of \nGRADEFor GRADE, we are treating RSV vaccination with any \nof the three licensed products as a single intervention\nGRADE: Grading of Recommendations, Assessment, Development and Evaluation. https://www.cdc.gov/acip/grade/index.html  \n22GSK’s Arexvy  vaccine in adults aged 50 –59 years at increased risk of severe RSV disease, \nBenefits: Geometric Mean Ratio (GMR) of neutralizing antibody titers1\na) Sero -response was defined as ≥4 -fold increase in the neutralization titer compared with pre -vaccination.\nb) GMR at 30 days post -vaccination. The manufacturer calculated GMR as Cohort 2 / Cohort 1a. However, here, the reciprocal is shown : Cohort 1a / Cohort \n2. GMR values >1 indicate higher geometric mean titers in Cohort 1a (adults 50 –59 at increased risk), compared with Cohort 2 (ad ults ≥60).\nc) Noninferiority objective was lower bound of the GMR confidence interval ≥0.67, when evaluating the GMR Cohort 1a / Cohort 2, and the lower limit of \nthe CI around the sero -response rate difference ≥ -10%, when evaluating Cohort 1a minus Cohort 2.\nd) Serological assays for the determination of antibodies against RSV -A and RSV -B are performed by neutralization assay. The corres ponding antibody titers \nwere expressed in ED60 (serum estimated dilution inducing 60% inhibition in plaque -forming units). Assessed at Day 31 , where Da y 1 was day of \nvaccination.\n1. Ferguson M, et al. Noninferior Immunogenicity and Consistent Safety of Respiratory Syncytial Virus Prefusion F Protein Vaccin e in Adults 50 -59 Years \nCompared to ≥60 Years of Age. Clin Infect Dis. 2024 Oct 15;79(4):1074 -1084. https://pubmed.ncbi.nlm.nih.gov/39099093/  N n with sero -responsea,\n30 days post -vaccinationN n with sero -responsea,\n30 days post -vaccinationGMR (95% CI)b, 30 \ndays post -vaccinationMet \nNoninferiority \nObjectivec\nCohort 1a: Adults aged 50 –59 \nyears at increased risk of severe \nRSV diseaseCohort 2: Adults aged ≥60 years Cohort 1a vs. Cohort 2\nRSV-Ad343 298 (86.9%) 342 275 (80.4%) 1.20 (1.05, 1.37) Yes\nRSV-Bd 343 280 (81.6%) 341 254 (74.5%) 1.25 (1.10, 1.41) Yes\nAbbreviations: CI = confidence interval; GMR = geometric mean ratio\n23Pfizer’s Abrysvo  vaccine in adults aged 50 –59 years at increased risk of severe RSV disease, \nBenefits: Geometric Mean Ratio (GMR) of neutralizing antibody titers1\na) Sero -response was defined as achieving a ≥4 -fold rise from baseline (before vaccination), if the baseline measurement was above the lower limit of \nquantification (LLOQ). If the baseline measurement was below the LLOQ, a postvaccination assay result ≥4 x LLOQ was considere d a sero -response.\nb) GMRs (ratio of geometric mean titers in Group 1, compared to Group 2) and 2 -sided CIs were calculated by exponentiating the diff erence in least square \nmeans and the corresponding CIs based on analysis of log -transformed titers using a regression model with population groups, bas eline log -transformed \ntiters and sex as covariates.\nc) Noninferiority objective was not defined for the subset of participants aged 50 -59 years. For the full study population aged 18 -59 years, noninferiority \ncriteria were met: lower bound of the GMR confidence interval ≥0.67, and the lower limit of the CI around the sero -response rate difference ≥ -10%.\n1. https://clinicaltrials.gov/study/NCT05842967 , https://pubmed.ncbi.nlm.nih.gov/37018468/ , https://www.cdc.gov/acip/downloads/slides -2024 -06-26-\n28/02 -RSV-Adult -Munjal -508.pdf , unpublished data obtained from manufacturerN n with sero -responsea,\n1 month post -vaccinationN n with sero -responsea,\n1 month post -vaccinationGMR (95% CI)b, one \nmonth post -vaccinationMet \nNoninferiority \nObjectivec\nGroup 1: Adults aged 50 –59 years \nat increased risk of severe RSV \ndiseaseGroup 2: Adults aged ≥60 years Group 1 vs. Group 2\nRSV-A 206 193 (93.7%) 534 450 (84.3%) 1.54 (1.33, 1.78) N/Ac\nRSV-B 207 195 (94.2%) 534 457 (85.6%) 1.52 (1.30, 1.79) N/Ac\nAbbreviations: CI = confidence interval; GMR = geometric mean ratio\n24Moderna’s mResvia  vaccine in adults aged 50 –59 years at increased risk of severe RSV \ndisease, Benefits: Geometric Mean Ratio (GMR) of neutralizing antibody titers1\na) Seroresponse  at a participant level was defined as a change from below the lower limit of quantification (LLOQ) to equal or above 4 x LLOQ , or at least a \n4-fold increase if baseline (pre -vaccine) was equal to or above the LLOQ.\nb) GMRs (ratio of geometric mean titers in Group 1, compared to Group 2) and 2 -sided CIs were estimated using an Analysis of Covari ance model, with log -\ntransformed antibody levels at Day 29 post -baseline as the dependent variable, treatment group as the explanatory variable, and log-transformed \nbaseline antibody level as a covariate. The resulting least square means, difference of least square means, and 95% CIs (base d on t-distribution) were \nback transformed to the original scale for the estimated geometric mean titer and GMR.\nc) Noninferiority objective was not defined for the subset of participants aged 50 -59 years. For the full study population aged 18 -59 years, noninferiority \ncriteria were met: lower bound of the GMR confidence interval ≥0.67, and the lower limit of the CI around the sero -response rate difference ≥ -10%.\n1. https://clinicaltrials.gov/study/NCT06067230 , https://pubmed.ncbi.nlm.nih.gov/38091530/ , unpublished data obtained from manufacturerN n with sero -responsea,\n28 days post -vaccinationN n with sero -responsea,\n28 days post -vaccinationGMR (95% CI)b, 28 \ndays post -vaccinationMet \nNoninferiority \nObjectivec\nGroup 1: Adults aged 50 –59 \nyears at increased risk of severe \nRSV diseaseGroup 2: Adults aged ≥60 years Group 1 vs. Group 2\nRSV-A 303 259 (85.5%) 1513 1119 (74.0%) 1.13 (1.01, 1.28) N/Ac\nRSV-B 302 201 (66.6%) 1511 853 (56.5%) 1.10 (0.99, 1.23) N/Ac\nAbbreviations: CI = confidence interval; GMR = geometric mean ratio\n25Outcome Importance Data SourcesEffect Estimate,\nGeometric mean titer ratioaPooled effect estimate, \nefficacyb (95% CI)\nin adults aged ≥60 yearsAdjustments to certainty \nassessment\nMedically attended RSV \nLRTDImportantThree phase 3 \nRCTs in adults \naged <60 \nyears1–3\nThree phase 3 \nRCTs in adults \naged ≥60 \nyears4–6Adults 50 –59 at increased risk vs. \nadults ≥60:\nRSV-A: 1.20 (95% CI: 1.05, 1.37)1\nRSV-B: 1.25 (95% CI: 1.10, 1.41)1\nRSV-A: 1.54 (95% CI: 1.33, 1.78)2\nRSV-B: 1.52 (95% CI: 1.30, 1.79)2\nRSV-A: 1.13 (95% CI: 1.01, 1.28)3\nRSV-B: 1.10 (95% CI: 0.99, 1.23)369.3% (51.7, 80.6)\nAssessed using 16 –23 months mean \nfollow up per participant4–6Indirectness (serious)c\nHospitalization for RSV \nrespiratory illnessCritical76.7% (8.3, 94.1)\nAssessed using 9 –16 months mean \nfollow up per participant4–6Indirectness (serious)c\nImprecision (very serious)d\nStrong associatione\nDeath due to RSV \nrespiratory illnessCritical Zero events observed Unable to evaluate\nCI: confidence interval, LRTD: lower respiratory tract disease, RCT: randomized controlled trial\na) Titers assessed through neutralization assay one month after vaccination. Data from participants aged <50 years were excluded .\nb) Pooled estimate using data from all interventional studies for each outcome generated using Mantel -Haenszel random effects model . Efficacy was calculated as 1 – incidence rate ratio. Events were included if they \noccurred >14 days post -vaccination.\nc) Serious concern for indirectness as the outcome was evaluated using immunobridging  data as a surrogate for vaccine efficacy and there is no established correlate of protection.\nd) Very serious concern for imprecision due to the confidence interval in adults 60 and older containing estimates for which dif ferent policy decisions might be considered, and for fragility of the estimate. Fragility refers \nto a situation in which estimates of the magnitude of effect and CIs may appear robust, but due to small numbers of events, r eallocation of <5 events from control to intervention group may render different results. \ne) The relative rate for this outcome was <0.5 with consistent evidence from all 3 studies, with no significant concern for conf ounding. Therefore, this was considered to be a large effect size.\n1. Ferguson M, et al. Noninferior Immunogenicity and Consistent Safety of Respiratory Syncytial Virus Prefusion F Protein Vaccin e in Adults 50 -59 Years Compared to ≥60 Years of Age. Clin Infect Dis. 2024 Oct \n15;79(4):1074 -1084. https://pubmed.ncbi.nlm.nih.gov/39099093/ \n2. https://clinicaltrials.gov/study/NCT05842967 , https://www.cdc.gov/acip/downloads/slides -2024 -06-26-28/02 -RSV-Adult -Munjal -508.pdf , unpublished data obtained from manufacturer\n3. https://clinicaltrials.gov/study/NCT06067230 , unpublished data obtained from manufacturer\n4. Papi  A, et al. Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older Adults. NEJM 2023; 388:595 –608. https://pubmed.ncbi.nlm.nih.gov/36791160/ , unpublished data obtained from manufacturer\n5. Walsh EE, et al. Efficacy and Safety of a Bivalent RSV Prefusion F Vaccine in Older Adults. N Engl J Med. 2023 Apr 20;388(16) :1465-1477. https://pubmed.ncbi.nlm.nih.gov/37018468 , unpublished data obtained from \nmanufacturer\n6. Wilson E, et al. Efficacy and Safety of an mRNA -Based RSV PreF  Vaccine in Older Adults. N Engl J Med. 2023 Dec 14;389(24):2233 -2244. https://pubmed.ncbi.nlm.nih.gov/38091530/ , unpublished data obtained from \nmanufacturerRSV vaccination in adults aged 50 –59 years at increased risk of severe RSV disease \nBenefits: randomized studies , immunobridging\n26Outcome Importance Data SourcesPooled effect estimate, \nVaccine Effectiveness (95% \nCI)aAdjustments to certainty \nassessment\nMedically attended RSV \nLRTDb ImportantThree case -control studies (test -\nnegative design) in adults ≥60 \nyears1–3 \nOne retrospective cohort study \n(target trial emulation) in adults \n≥60 years478% (74, 82)c Indirectness (serious)d\nStrong associatione\nHospitalization for RSV \nrespiratory illnessCritical 80% (73, 85)c Indirectness (serious)d\nStrong associatione\nDeath due to RSV \nrespiratory illnessCritical No data available Unable to evaluateRSV vaccination in adults aged 50 –59 years at increased risk of severe RSV disease  \nBenefits: observational studies\nCI: confidence interval, LRTD: lower respiratory tract disease\na)Pooled estimate using data from observational studies for each outcome generated using Mantel -Haenszel random effects model with  weights assigned using standard error back \ncalculation.\nb)Surrogate outcome was used to evaluate this outcome: RSV -associated ED visit, or either RSV -associated ED visit or hospitalizati on, depending availability by study.\nc)Pooled effectiveness estimate reflects a mean or median of 2 –4 months after vaccination in each study.\nd)Serious concern for indirectness because study participants were from the general population 60 and older, not 50 -59 with condit ions that increase risk.\ne)The relative rate for this outcome was <0.5 with consistent evidence from all 4 studies, with no significant concern for conf ounding. Therefore, this was considered to be a large effect size.\n1.Surie D, et al. RSV Vaccine Effectiveness Against Hospitalization Among US Adults 60 Years and Older. JAMA. 2024 Oct 1;332(13 ):1105-1107. https://pubmed.ncbi.nlm.nih.gov/39230920/  \n2.Payne AB, et al. Respiratory syncytial virus (RSV) vaccine effectiveness against RSV -associated hospitalisations  and emergency department encounters among adults aged 60 years and older \nin the USA, October, 2023, to March, 2024: a test -negative design analysis. Lancet. 2024 Oct 19;404(10462):1547 -1559. https://pubmed.ncbi.nlm.nih.gov/39426837/  \n3.Pfizer -sponsored study: Tartof  SY , et al. Estimated Vaccine Effectiveness for Respiratory Syncytial Virus -Related Lower Respiratory Tract Disease. JAMA Netw  Open. 2024 Dec \n2;7(12):e2450832. https://pubmed.ncbi.nlm.nih.gov/39671195/  \n4.Bajema KL, et al. Respiratory syncytial virus vaccine effectiveness among US veterans, September, 2023 to March 2024: a targe t trial emulation study. Lancet Infect Dis. 2025 Jan 20:S1473 -\n3099(24)00796 -5. https://pubmed.ncbi.nlm.nih.gov/39848264/  \n27a)Within 6 months after study intervention.\nb)Pooled estimate using data from all studies for this outcome generated using a Mantel -Haenszel fixed effect model. Data were lim ited \nto participants aged 50 –59 years.\nc)Serious concern for imprecision due to the confidence interval containing estimates for which different policy decisions migh t be \nconsidered.\nd)Serious concern for inconsistency because the point estimates between the studies differed substantially, although the confid ence \nintervals overlapped.\ne)Within 42 days after vaccination.\n1.Ferguson M, et al. Noninferior Immunogenicity and Consistent Safety of Respiratory Syncytial Virus Prefusion F Protein Vaccin e in Adults \n50-59 Years Compared to ≥60 Years of Age. Clin Infect Dis. 2024 Oct 15;79(4):1074 -1084. https://pubmed.ncbi.nlm.nih.gov/39099093/ , \nunpublished data obtained from manufacturer\n2.https://clinicaltrials.gov/study/NCT05842967 , https://www.cdc.gov/acip/downloads/slides -2024 -06-26-28/02 -RSV-Adult -Munjal -\n508.pdf , unpublished data obtained from manufacturerOutcome Importance Data SourcesPooled effect \nestimate, relative risk \n(95% CI)Concerns in certainty \nassessment\nSerious adverse events \n(SAEs)aCritical Two phase 3 RCTs in \nadults aged <60 years at \nincreased risk of severe \nRSV disease1,21.13 (0.50, 2.59)bImprecision (serious)c\nInconsistency (serious)d\nInflammatory neurologic \neventseCritical Zero events observed Unable to evaluateRSV vaccination  in adults aged 50 –59 years at increased risk of severe RSV disease\nHarms\n28Summary of GRADE for RSV vaccination in adults aged 50 –59 years at \nincreased risk of severe RSV disease\nOutcome​ ImportanceDesign\n(# of studies)​Findings​\nIn adults aged 50 -59 years at increased risk of severe RSV \ndisease:Evidence\ntype​\nBenefits\nMedically attended RSV \nlower respiratory tract \ndisease (LRTD)ImportantRCT (3) RSV vaccination likely reduces medically attended RSV LRTD Moderate\nObservational (3) RSV vaccination may reduce medically attended RSV LRTD Low\nHospitalization for RSV \nrespiratory illnessCriticalRCT (3) RSV vaccination may reduce hospitalization for RSV respiratory illness Low\nObservational (4) RSV vaccination may reduce hospitalization for RSV respiratory illness Low\nDeath due to RSV \nrespiratory illnessCritical RCT (3) Zero events observedUnable to \nevaluate\nHarms\nSerious adverse events​ Critical RCT (2)RSV vaccination may result in little to no difference in serious adverse \neventsLow\nInflammatory neurologic \neventsCritical RCT (2) Zero events observedUnable to \nevaluate\nRCT: randomized controlled trial\n29•Population benefits of RSV vaccination compared with risk of Guillain -\nBarre syndrome (GBS), for protein subunit vaccines\n•Duration of vaccine protection and potential to restore protection through \nrevaccination\n•Immunogenicity in immunocompromised personsAdditional information on benefits/harms for adults aged \n50–59 years at increased risk of severe RSV disease\n30▪On January 7th, the U.S. Food and Drug Administration ( FDA) required revision of the \nPrescribing Information for GSK’s Arexvy2 and Pfizer’s Abrysvo3 Warnings and Precautions \nsection to include  the following: \n▪The results of a postmarketing  observational study suggest an increased risk of Guillain -Barré syndrome \n(GBS) during the 42 days following vaccination with [ Abrysvo /Arexvy ].\n▪Available data suggest that risk is similar to, and potentially greater than, that of other \ncurrently licensed and recommended adult vaccines.\n▪The analyses of all GBS cases based on claims data suggest an increased risk of GBS during the 42 days \nfollowing vaccination, […] with an estimated 9 excess cases of GBS per million doses of Abrysvo , and an \nestimated 7 excess cases of GBS per million doses of Arexvy  administered to individuals 65 years of age \nand older.Available FDA data support existence of increased risk of \nGBS after protein subunit RSV vaccination1 in adults ≥65yrs\n1.GSK’s Arexvy  and Pfizer’s Abrysvo  are protein subunit RSV vaccines. Moderna’s mResvia  is an mRNA RSV vaccine, not a protein subunit vaccine. To date, Moderna’s \nmResvia  vaccine has NOT been associated with increased risk of Guillain -Barré syndrome. Post -licensure safety surveillance for mResvia  began recently in June 2024.\n2.https://www.fda.gov/media/167805/download  \n3.https://www.fda.gov/media/168889/download  \n31▪The Work Group emphasized that risk of Guillain -Barre syndrome (GBS) associated with \nprotein subunit RSV vaccines1 should be considered in the context of the public health \nbenefits of RSV vaccination.\n▪In June and October 2024 , ACIP reviewed results of mathematical modeling analyses \ncomparing the numbers of RSV -associated hospitalizations, intensive care unit (ICU) \nadmissions, and deaths preventable per 1 million persons vaccinated vs. the numbers of \npotential vaccine -attributable GBS cases.2\n▪This analysis has been updated to account for the most up to date information on protein \nsubunit RSV vaccine effectiveness, duration of protection, and GBS risk1, and has been applied \nto adults aged 50 –59 years at increased risk of severe RSV disease.\n▪The background risk of GBS in a study population influences the excess GBS case estimates and may differ \nbetween studies, precluding direct comparisons to excess GBS case estimates from other vaccine studies or \npopulations.Available FDA data support existence of increased risk of \nGBS after protein subunit RSV vaccination1 in adults ≥65yrs\n1.GSK’s Arexvy  and Pfizer’s Abrysvo  are protein subunit RSV vaccines. Moderna’s mResvia  is an mRNA RSV vaccine, NOT a protein subunit vaccine. To date, Moderna’s \nmResvia  vaccine has NOT been associated with increased risk of Guillain -Barré syndrome. Post -licensure safety surveillance for mResvia  began recently in June 2024.\n2.https://www.cdc.gov/acip/downloads/slides -2024 -10-23-24/06 -RSV-Adult -Melgar -508.pdf  \n321.Range of outcomes avertable was calculated using adjusted 95% confidence interval of RSV -associated incidence of the outcome obs erved in RSV -NET.\n2.FDA self -controlled case series analysis, among CMS Medicare beneficiaries ≥65 years with Parts A, B, and D coverage who did not  have a GBS claim in the 365 days before vaccination. Analysis based on \ndiagnoses of GBS in inpatient claims data in risk interval (1 –42 days after RSV vaccination) compared to control interval (43 –90 days after RSV vaccination). GBS cases identified using ICD -10 diagnosis of GBS in \nprimary position of inpatient claims coding with chart verification requiring Brighton Collaboration Level 1 –3 certainty. Estima tes adjusted for outcome -dependent observation time, seasonality, and (when \nchart review could not be performed) the positive predictive value of diagnostic codes in identifying chart -confirmed GBS cases.  Analysis includes patients with RSV vaccinations only through January 28, 2024 \nto allow for 90 -day post -vaccination observation and 90% or greater claims data completeness. Claims data through July 13, 2024.  \n3.Although CMS data were limited to Medicare beneficiaries aged ≥65 years, results are extrapolated here to apply to adults age d 50-59 years.\n4.Credible range spans the lowest lower bound and highest upper bound of attributable risk estimates for the GSK and Pfizer RSV  vaccines.Estimated RSV -associated outcomes1 preventable  over 3 RSV Seasons  vs. attributable risk of Guillain -\nBarre syndrome (GBS) estimated from self -controlled case series analysis through FDA -CMS partnership \ndata among adults aged ≥65 years, 42 -day risk interval2\nBase case\nAbsolute risk from adults ≥65 years applied \ndirectly to adults aged 50 -59 years:\n0–184 attributable  cases of GBS per 1 \nmillion people vaccinated\nCredit: Dr. David Hutton, U. MichiganPer 1 Million Doses of Protein Subunit  RSV Vaccines Administered to Adults \nAged 50 –59 Years3 at Increased Risk of Severe RSV Disease :\n1304302,000\n -  1,000  2,000  3,000  4,000  5,000  6,000  7,000Hospitalizations\nICU Admissions\nDeaths\n(30–260)(150 –830)(700 –3,800)\n33•In the clinical trials, protection provided by a single dose of RSV vaccine appears to wane over time.1,2,3 \n-Clinical trial data are available through 2 –3 RSV seasons, depending on manufacturer. \n-Do not yet have real -world effectiveness data beyond the first RSV season.\n•Clinical trial efficacy data evaluating revaccination are available only from GSK’s pivotal phase 3 trial (12 -month \nrevaccination interval).1\n-Clinical efficacy in GSK’s pivotal phase 3 trial did not improve after revaccination at a 12 -month interval.What do we know so far about duration of protection and the need \nfor revaccination with adult RSV vaccines? \n1. Ison MG, et al. Efficacy and Safety of Respiratory Syncytial Virus (RSV) Prefusion F Protein Vaccine (RSVPreF3 OA) in Older A dults Over 2 RSV Seasons. Clin Infect Dis. 2024 Jun 14;78(6):1732 -1744. \nhttps://pubmed.ncbi.nlm.nih.gov/38253338/   \n2. Walsh EE, Eiras  D, Woodside J, et al. Efficacy, Immunogenicity, and Safety of the Bivalent RSV Prefusion F ( RSVpreF ) Vaccine in Older Adults Over 2 RSV Seasons, Clinical Infectious Diseases, 2025; ciaf061. Feb \n2025. https://doi.org/10.1093/cid/ciaf061  \n3. Das R. Update on Moderna’s RSV vaccine, mRESVIA  (mRNA -1345), in adults ≥60 years of age [Presentation slides]. Presented at the Advisory Committee on Immunization Practices me eting, Atlanta, GA; June 26, \n2024. https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2024 -06-26-28/04 -RSV-Adult -Das-508.pdf\n34Clinical efficacy of 1 and 2 doses of GSK RSV vaccine ( Arexvy ) from \nGSK’s phase 3 clinical trial \nGSK RSV vaccine doses Vaccine efficacy (%) against RSV -\nassociated lower respiratory tract \ndisease\nSingle dose, season 1 only (median \nfollow -up 6.7 months during season 1)182.6 (96.95% CI: 57.9, 94.1)\nSingle dose, season 2 only (median \nfollow -up 6.3 months during season 2)256.1 (95% CI: 28.2, 74.4)\nTwo doses, season 2 only (median \nfollow -up 6.3 months during season 2)355.9 (95% CI: 27.9, 74.3)\nCI=confidence interval\nIson MG, et al. Efficacy and Safety of Respiratory Syncytial Virus (RSV) Prefusion F Protein Vaccine (RSVPreF3 OA) in Older A dults Over 2 RSV Seasons. Clin Infect Dis. 2024 Jun 14;78(6):1732 -1744. \nhttps://pubmed.ncbi.nlm.nih.gov/38253338/  \n1.Efficacy of 1 dose RSVPreF3 OA given pre -season 1 in preventing RSV -LRTD over season 1.\n2.Efficacy of 1 dose RSV PreF3 OA given pre -season 1 in preventing RSV -LRTD over season 2. \n3.Efficacy of 1 dose RSV PreF3 OA given pre -season 1 and a 2nd dose given pre -season 2 in preventing RSV -LRTD over season 2. Analysis includes data collected from participants who received R SVPreF3 OA as \ndose 1 and dose 2 for the analysis of the revaccination regimen, and from participants who received placebo as dose 1 and 2 ( com parator group).Revaccination at 12 \nmonths did not improve \nprotection against \nclinical disease \n35•In the clinical trials, protection provided by a single dose of RSV vaccine appears to wane over time.1,2,3 \n-Clinical trial data are available through 2 –3 RSV seasons, depending on manufacturer. \n-Do not yet have real -world effectiveness data beyond the first RSV season.\n•Clinical trial efficacy data evaluating revaccination are available only from GSK’s pivotal phase 3 trial (12 -month \nrevaccination interval).1\n-Clinical efficacy in GSK’s pivotal phase 3 trial did not improve after revaccination at a 12 -month interval.\n•Immunogenicity data at various revaccination intervals are being studied\n-GSK immunogenicity data at 12 -, 24-, and 36 -month revaccination intervals have shown a weaker humoral \nimmune response compared with the response after dose 1.4\n-Pfizer immunogenicity data at a 12 -month revaccination interval has also shown a weaker humoral immune \nresponse compared with the response after dose 1.5\n-Moderna immunogenicity data at 12 - and 24 -month revaccination intervals have met prespecified non-\ninferiority objectives compared with dose 1,3,6 but revaccination with a 24 -month interval showed lower peak \nGMT compared with dose 1.What do we know so far about duration of protection and the need \nfor revaccination with adult RSV vaccines? \n1. Ison MG, et al. Efficacy and Safety of Respiratory Syncytial Virus (RSV) Prefusion F Protein Vaccine (RSVPreF3 OA) in Older Adults  Over 2 RSV Seasons. Clin Infect Dis. 2024 Jun 14;78(6):1732 -1744. https://pubmed.ncbi.nlm.nih.gov/38253338/   \n2. Walsh EE, Eiras  D, Woodside J, et al. Efficacy, Immunogenicity, and Safety of the Bivalent RSV Prefusion F ( RSVpreF ) Vaccine in Older Adults Over 2 RSV Seasons, Clinical Infectious Diseases, 2025; ciaf061. Feb 2025. https://doi.org/10.1093/cid/ciaf061  \n3. Das R. Update on Moderna’s RSV vaccine, mRESVIA  (mRNA -1345), in adults ≥60 years of age [Presentation slides]. Presented at the Advisory Committee on Immunization Practices me eting, Atlanta, GA; June 26, 2024. https://www.cdc.gov/acip/downloads/slides -2024 -06-26-\n28/04 -RSV-Adult -Das-508.pdf \n4.Gerber, S. Arexvy  (Adjuvanted RSVPreF3). Presented at the Advisory Committee on Immunization Practices meeting, Atlanta, GA; April 16, 2025. https://www.cdc.gov/acip/downloads/slides -2025 -04-15-16/03 -Gerber -Adult -RSV-508.pdf\n5. Walsh EE, et al. Respiratory Syncytial Virus Prefusion F Vaccination: Antibody Persistence and Revaccination. J Infect Dis. 2 024 Oct 16;230(4):e905 -e916. https://pubmed.ncbi.nlm.nih.gov/38606958/  \n6. Shaw CA et al. Safety and Immunogenicity of an mRNA -Based RSV Vaccine Including a 12 -Month Booster in a Phase 1 Clinical Trial in Healthy Older  Adults, The Journal of Infectious Diseases , Volume 230, Issue 3, 15 September 2024, Pages e647 –\ne656,  https://pubmed.ncbi.nlm.nih.gov/38385566/  \n36Revaccination summary \n•Efficacy data with revaccination at 12 months did not \nshow any improvement in clinical protection \n•Revaccination DOES elicit a “boost” in neutralizing \nantibody immune response\n•For GSK, neutralizing antibody response does not \nappear to reach post -dose 1 antibody levels, even after \nwaiting 3 years to revaccinate after the initial dose\n•For Moderna, neutralizing antibody response to \nrevaccination at 12 and 24 -months met non-inferiority \ncriteria*  when compared with titers post -dose 1, but \nwere lower with the 24 -month interval\n•Cellular immune response data available from \nGSK shows that revaccination boosts T -cell response to \npost -dose 1 level or higher •No clear trend yet visible in available data indicating \nlonger revaccination intervals yield more robust \nantibody responses\n-Would longer revaccination intervals result in a stronger \nneutralizing antibody response? How long would that be \n(5 years)? \n•Are the “boosted” revaccination antibody responses \nsufficient to provide clinical protection (even if lower \nthan the post -dose 1 response)?\n•What is the relative importance of humoral versus \ncellular immune responses in providing protection \nagainst clinical disease?\n•Do immunocompromised adults experience different \nimmune responses to revaccination?Knowns Unknowns\n* Prespecified non -inferiority criteria were met when the lower bounds of the 95% confidence interval (CI) of the Geometric Mean  Titer Ratio (GMR) of RSV -\nA and RSV -B neutralizing antibodies one month after dose #2 / one month after dose #1 were >0.667. 24 -month revaccination GMR of  RSV-A was 0.719 (95% \nCI: 0.68, 0.76); 24 -month GMR of RSV -B was 0.705 (95% CI: 0.67, 0.74). Despite the statistically significant difference, prespecified non -inferiority criteria \nwere met because the lower bound of the 95% CI was >0.667. \n37Summary of GSK Arexvy  immunogenicity studies \namong adults with immune compromise\n•Trial included adults aged ≥18 years with renal or lung transplant \n•One month after a single dose of Arexvy , these participants had lower RSV neutralizing antibody \ntiters, compared with immunocompetent adults aged ≥50 years\n•After a second dose of Arexvy  one month after the first, RSV neutralizing antibody titers increased \nand were similar to those in immunocompetent adults aged ≥50 years at 2 months post -vaccination\n•Measures of cellular immunity after Arexvy  vaccination were similar between immunocompromised \nparticipants and immunocompetent participants\n•No specific safety concerns identified. O ne participant experienced renal transplant rejection after \nRSV vaccination*. \n*Not interpreted as vaccine -related by the investigator\n38Summary of Pfizer Abrysvo immunogenicity studies \namong adults with immune compromise \n•Trial included adults aged ≥18 years with autoimmune disorders on immunomodulator therapy, solid \norgan transplant, end -stage renal disease on dialysis, or non -small cell lung cancer on therapy\n•One month after a single dose of Abrysvo , these participants had similar RSV neutralizing antibody \ntiters, compared with immunocompetent adults aged ≥60 years from Pfizer’s main phase 3 trial\n•The neutralizing antibody response in participants with autoimmune disorders on immunomodulator \ntherapy and solid organ transplant appeared lower than in adults with end -stage renal disease\n•A second dose of Abrysvo  one month after the first did not appreciably increase neutralizing antibody \ntiters \n•No specific safety concerns identified. O ne participant experienced renal transplant rejection* and \none participant experienced lung transplant rejection* after RSV vaccination. \n*Not interpreted as vaccine -related by the investigator\n39Benefits and Harms of RSV vaccine in  adults aged 50 –59 years at increased \nrisk of severe RSV disease\n▪How substantial are the desirable anticipated effects among adults aged 50 –59 years at increased \nrisk of severe RSV disease\n▪How substantial are the undesirable anticipated effects among adults aged 50 –59 years at \nincreased risk of severe RSV disease?\n▪Do the desirable effects outweigh the undesirable effects among adults aged 50 –59 years at \nincreased risk of severe RSV disease?Minimal Small Moderate Large Varies Don’t know\nMinimal Small Moderate Large Varies Don’t know\nFavors intervention (RSV vaccine)\nFavors comparison (no vaccine)\nFavors both\nFavors neither\nUnclearMinority \nopinion\nValues and preferences\n- Do adults aged 50 –59 years at increased risk of severe RSV disease  feel the \ndesirable effects of RSV vaccination are large relative to the undesirable effects? \n- Is there important variability in how these adults value the main outcomes?\n416.5\n10.6\n10.712.2\n17.1\n25.132.7\n41.0\n33.148.6\n31.2\n31.1\n0 25 50 75 100Age ≥75 (N=326)Age 60 -74 (N=977)Age 18 -59 (N=2,799)\nWeighted %Very concerned Moderately concerned A little concerned Not at all concernedConcern About Getting RSV Disease Among Adults Aged ≥18 Years, by \nAge Group, Omnibus Surveys, April 4 –26, 2024 (N=4,102)\nOmnibus Surveys: data for this analysis were collected through the Ipsos KnowledgePanel  and NORC AmeriSpeak  Omnibus Surveys, which use probability -based panels to survey a nationally representative \nsample of U.S. adults aged 18 years and older. CDC fields questions about vaccination status, intent, knowledge, attitudes, b eliefs, and behaviors on each survey for 2 waves each month, for a combined \nsample size of ~4,000 respondents. These slides present results from April 2024. Data were weighted to represent the non -institu tionalized U.S. population and mitigate possible non -response bias. All \nresponses are self -reported.\n42Behavioral & Social Drivers of RSV Vaccination Among Adults Aged 60 –74 \nYears at Increased Risk** for Severe RSV Disease, November 2024\nNational Immunization Survey -Adult COVID Module (NIS -ACM)\n**A respondent was considered to be at increased risk for severe RSV disease if they had any of the following: chronic lung d iseases, diabetes with insulin use, heart conditions, immunocompromised state, solid organ or blood stem \ncell transplant (including bone marrow transplant), cancer, liver disease, sickle cell disease or thalassemia, or currently l ives in a nursing home.\nNIS-ACM methods: Data from adults age ≥18 years are collected by telephone interview using a random -digit -dialed sample of cell telephone numbers  stratified by state, the District of Columbia, five local jurisdictions (Bexar County \nTX, Chicago IL, Houston TX, New York City NY, and Philadelphia County PA), and Puerto Rico and the U.S. Virgin Islands. Data are weighted to represent the non -institutionalized U.S. population and mitigate possible bias that can \nresult from an incomplete sample frame (exclusion of households with no phone service or only landline telephones) or non -respon se. All responses are self -reported. For more information about the survey, see \nhttps://www.cdc.gov/nis/about/index.html  and https://www.cdc.gov/nis/media/pdfs/2025/02/NISACMQuestionnaireQ12025_508 -2_2025.pdf.496479\n32\n020406080100\nConcerned about\nRSV diseaseConfidence in RSV\nvaccine safetyConfidence that\nRSV vaccine is\nimportant\nprotectionHealth care\nprovider\nrecommended\nRSV vaccineWeighted % of Respondents Selecting \nResponse Option(s) to Questions About \nRSV and RSV Vaccine Responses to questions: \n“Very or moderately concerned about \ngetting RSV”\n“Thinks the RSV vaccine is completely \nor very safe”\n“Thinks the RSV vaccine is very or \nsomewhat important to protect \nyourself against RSV”\n“Doctor, nurse, or other health \nprofessional recommended that you \nget an RSV vaccine since Fall 2023”\n432122222426272727273030303030333334343535353537373717201715131019171414161119221014161412141591213124442\n374447\n373935374039\n40272742372430373234\n303531311816\n241814\n2616212217151925211617\n2522162016\n27161820\n0255075100\nAug25-31\nSep1-7\nSep8-14\nSep15-21\nSep22-28\nSep29-Oct5\nOct6-12\nOct13-19\nOct20-26\nOct27-Nov2\nNov3-9\nNov10-16\nNov17-23\nNov24-30\nDec1-7\nDec8-14\nDec15-21\nDec22-28\nDec29-Jan4\nJan5-11\nJan12-18\nJan19-25\nJan26-Feb1\nFeb2-8\nFeb9-15Weighted %\n3031313131323535363740414142434444444446464646464647121013131513141699776787798115115511123939403733363732\n33373432292833\n2525283226\n2926\n29272322192017202119141721171920252417\n2424191618201720222020\n0255075100\nAug18-24\nAug25-31\nSep1-7\nSep8-14\nSep15-21\nSep22-28\nSep29-Oct5\nOct6-12\nOct13-19\nOct20-26\nOct27-Nov2\nNov3-9\nNov10-16\nNov17-23\nNov24-30\nDec1-7\nDec8-14\nDec15-21\nDec22-28\nDec29-Jan4\nJan5-11\nJan12-18\nJan19-25\nJan26-Feb1\nFeb2-8\nFeb9-15Weighted %RSV Vaccination Status and Intent Among Adults Aged ≥75 Years and 60 –\n74 Years at Increased Risk**  for Severe RSV, through February 15, 2025\nNational Immunization Survey -Adult COVID Module (NIS -ACM)\nProbably or definitely will not get RSV vaccine\nProbably will get RSV vaccine or unsure\nDefinitely will get RSV vaccine\nReceived RSV vaccineWeekly RSV Vaccination Status and Intent, NIS -ACM\n**A respondent was considered to be at increased risk for severe RSV disease if they had any of the following: chronic lung d iseases, diabetes with insulin use, heart conditions, immunocompromised state, solid organ or blood \nstem cell transplant (including bone marrow transplant), cancer, liver disease, sickle cell disease or thalassemia, or curren tly lives in a nursing home.\nNIS-ACM methods: Data from adults age ≥18 years are collected by telephone interview using a random -digit -dialed sample of cell telephone numbers  stratified by state, the District of Columbia, five local jurisdictions (Bexar \nCounty TX, Chicago IL, Houston TX, New York City NY, and Philadelphia County PA), and Puerto Rico and the U.S. Virgin Islands . Data are weighted to represent the non -institutionalized U.S. population and mitigate possible bias \nthat can result from an incomplete sample frame (exclusion of households with no phone service or only landline telephones) o r non-response. All responses are self -reported. For more information about the survey, see \nhttps://www.cdc.gov/nis/about/index.html.Aged ≥75 years \n•47% (95% CI: 45.0 -48.3) received \nan RSV vaccine\n•12% (95% CI: 6.1 -17.5) definitely \nwill get vaccinated\nAged 60 –74 years at increased risk\n•37% (95% CI: 34.1 -40.6) received \nan RSV vaccine\n•12% (95% CI: 5.8 -18.5) definitely \nwill get vaccinatedAdults Aged 60 –74 Years at Increased Risk (n=18,880) Adults Aged ≥75 Years (n=95,706)\nRisk of Guillain -Barre Syndrome (GBS)\n1. Scherer LD, Shaffer VA, Patel N, Zikmund -Fisher BJ. Can the vaccine adverse event reporting system be used to increase vaccine a cceptance and trust? Vaccine. 2016 May 5;34(21):2424 -2429. https://pubmed.ncbi.nlm.nih.gov/27049120/  \n2. Prosser LA, Payne K, Rusinak  D, et al. Valuing health across the lifespan: health state preferences for seasonal influenza illnesses in patients of differ ent ages. Value Health. 2011;14(1):135 -143. https://pubmed.ncbi.nlm.nih.gov/21211495/  There are no data assessing how adults value protection against RSV \nrelative to potential risk of GBS.\nA few considerations: \n•Adults are willing to accept some rate of vaccine -associated adverse \nevents for the benefit of preventing disease1 \n•Individual baseline and vaccine -associated risk of GBS may differ by \nage group and presence of chronic conditions \n•Willingness to accept risk of GBS after vaccination may differ by age \nand health status and perceived risk of RSV -associated disease2\n44\n45•About 20% of adults aged 18 –59 years say they are very or moderately \nconcerned about RSV, compared with approximately 30 –35% of adults \naged ≥60 years.\n•Uptake of RSV vaccine through February 2025 was 37 –47% among \nadults aged ≥60 years.\n•We do not have data on how adults value protection against RSV versus \npotential risk of GBS, but this may vary by age or other factors. Values: summary of the available evidence\nAdults aged 50 –59 years at increased risk of severe RSV disease\nValues\nNo Probably no Probably Yes Yes Varies Don’t know\nImportant uncertainty or variability\nProbably important uncertainty or variability\nProbably not important uncertainty or variability\nNo important uncertainty or variability\nNo known undesirable outcomes•Do adults aged 50 –59 years at increased risk of severe RSV disease feel that \nthe desirable effects of RSV vaccination are large relative to the undesirable \neffects?\n•Is there important uncertainty about, or variability in, how much  adults aged 50 –\n59 years at increased risk of severe RSV disease value the main outcomes?\n46Minority \nopinion\nIs it feasible to implement RSV vaccination for adults aged 50 –59 years at increased risk of \nsevere RSV disease ?Acceptability\nWould recommending RSV vaccination for adults aged 50 –59 years at increased \nrisk of severe RSV disease  be acceptable to key stakeholders?\nFeasibility\n48Top RSV vaccination concerns and issues among adults age d60–74 years \nwith high -risk condition s*, Omnibus Surveys , December 12 –30, 2024\nOmnibus Surveys: Data for this analysis were collected through the Ipsos KnowledgePanel  and NORC AmeriSpeak  Omnibus Surveys, which use probability -based panels to survey a nationally representative sample of U.S. \nadults aged 18 years and older. CDC fields questions about vaccination status, intent, knowledge, attitudes, beliefs, and beh aviors on each survey for 2 waves each month, for a combined sample size of ~4,000 respondents. \nThis slide presents results from December 2024. Data were weighted to represent the non -institutionalized U.S. population and mi tigate possible non -response bias. All responses are self -reported.*Includes self -reported chronic lung disease, heart conditions, solid organ or blood stem cell transplant, cancer (excluding bas al cell carcinoma and squamous cell carcinoma), diabetes, liver \ndisease, sickle cell disease or thalassemia, BMI (body mass index) ≥40, and immunocompromised state. \nOther response options included: \"Have not had time,\" \"Vaccine fatigue,\" \"Not eligible/ unsure if eligible,\" \"Too close to an other vaccine,\" \"Have enough immunity,\" \"Concerned about \neffectiveness,\" \"Other,\" \"Cost,\" \"Got sick from past vaccine,\" \"Could not find vaccine,\" \"Allergic/other medical reason.\"\n\n7.2%22.0%\n13.2%37.5%\n20.1%\n0%10%20%30%40%50%60%70%80%90%100%% of respondents selecting response option (n=926)\nNever Sometimes Half the time Most of the time Always\nUnpublished data —CDC/University of Iowa/RAND survey conducted 6/3 -6/24/24. Question respondents (N=926) included Family Medicine  providers (N=300), General Internists \n(N=306),  Pharmacists (N=295), and Pediatricians (N=25).58% of respondents report checking RSV vaccination eligibility for their adult \n(aged  ≥60 years) patients prior to an appointment most or all the time\n49\n36.4%\n28.0%\n24.9%\n22.5%\n22.1%\n20.8%\n13.2%\n12.1%\n9.1%\n8.4%\n6.0%\n5.5%\n4.3%\n4.0%\n3.5%\n2.0%\n1.4%0% 20% 40% 60% 80% 100%\nThe patient will refuse vaccination\nThe patient has concerns about their out-of-pocket vaccination cost\nPatients are tired of hearing about vaccines in general\nThey have a medical reason for not getting vaccinated\nThere isn’t enough time during a visit to discuss RSV vaccines\nOther recommended vaccines for this age group are a bigger priority for me\nThere isn’t enough time during a visit to vaccinate\nOther\nRecommending COVID-19 vaccination could increase general vaccine…\nPatients are tired of hearing about RSV vaccines\nRelatively high level of resistance to RSV vaccines in my community\nPatients in this age group are unlikely to experience severe RSV symptoms\nVaccination provides insufficient protection against RSV for this age group\nPatients in this age group are unlikely to get RSV\nVaccination doesn’t reduce RSV severity for this age group\nThe RSV vaccine is unsafe for patients in this age group\nPrior RSV makes vaccination is unnecessary for this age group% of respondents selecting response option (n=836)Anticipated vaccine refusal, patient financial concerns, and perceived patient \nvaccine fatigue were the top reasons for not recommending RSV vaccination\n50 Unpublished data —CDC/University of Iowa/RAND survey conducted 6/3 -6/24/24. Respondents for this question included Family Medicin e providers, General Internists, \nPharmacists, and Pediatricians. Respondents could select multiple answer choices. N=836. \nPotential barriers to implementation of a risk -based \nrecommendation for RSV vaccine among adults aged 50 –59 years\n•Vaccine acquisition cost is relatively high\n-Costly upfront investment to carry RSV vaccines\n•Most RSV vaccines are administered in pharmacies\n-Risk assessment and billing for risk -based recommendations may be challenging\n•Increased vaccine schedule complexity for adults\n-Limited time to discuss vaccines at appointments\n-Increasing number of adult vaccines\n-Multiple adult RSV vaccine products with different temperature requirements \nfor storage and handling \n51\n52•Approximately 50% of adults aged 60 –74 years with risk conditions have \nno concerns about RSV vaccine\n- Among those with concerns, top responses indicated lack of knowledge about RSV \nvaccine, concern about serious side effects and lack of provider recommendation\n•Providers check RSV vaccine eligibility about 60% of the time\n-Top barriers for making a recommendation are related to concern about \npatient vaccine fatigue and vaccine refusal \n•Other implementation barriers include cost, challenges of a risk -based \nrecommendation in pharmacy settings, and schedule complexity Acceptability and Feasibility: Summary of the available evidence \nAdults aged 50 –59 years at increased risk of severe RSV disease \nAcceptability\n•Would recommending RSV vaccines for adults aged 50 -59 years at \nincreased risk of severe RSV disease be acceptable to key \nstakeholders?\nNo Probably No Probably Yes Yes Varies Don’t know\n53\nFeasibility\n•Is it feasible to implement RSV vaccination among adults aged 50 -59 \nyears at increased risk of severe RSV disease? \nNo Probably No Probably Yes Yes Varies Don’t know\n54Minority \nopinion\nResource Use\nIs an RSV vaccine program for adults aged 50 –59 years at increased risk \nof severe RSV disease a reasonable and efficient allocation of resources\nWork Group considerations regarding societal resource use \ntoward RSV vaccination in older adults at current list prices\n•RSV vaccination for adults aged 50 –59 years with risk factors for severe RSV disease \nhas an incremental cost -effectiveness ratio (ICER) of $43,070 (3 -year time horizon for \nprotein subunit vaccines) to $152,293 (2 -year time horizon for mRNA vaccine)\n•Vaccination is likely cost -saving for certain risk conditions \n•Substantial uncertainty in key parameters that impact cost effectiveness:\n-Uncertainty in incidence of medically attended RSV illness, particularly hospitalizations\n-Uncertainty in RSV -attributable mortality\n-Uncertainty in duration of protection from a single dose of RSV vaccination\n-Real -world vaccine effectiveness of Moderna mResvia ; analyses currently rely on clinical trial efficacy \nestimates\n•If RSV vaccine list prices were substantially reduced, then RSV vaccination may be a cost -\neffective intervention for a broader adult population\n56\nResource use\n•Is RSV vaccination a reasonable and efficient allocation of resources in \nadults aged 50 -59 years at increased risk of severe RSV disease?\nNo Probably No Probably Yes Yes Varies Don’t know\n57\nEquity\nWhat would be the impact on health equity of recommending RSV \nvaccination for:\nAdults aged 50 –59 years at increased risk of severe RSV disease?\n58\nMedian age of non -pregnant adults* aged ≥18 years with RSV -\nassociated hospitalizations by race and ethnicity** — RSV-NET, \n2014 –2015 to 2022 –2023\nUnweightedWeighted\n%Median \nAgeInterquartile \nrange (IQR)\nOverall 17,847 - 69 (58–81)\nWhite 10,755 62.2 73 (63–82)\nBlack 3,529 20.4 62 (50–71)\nHispanic 1,434 8.3 62 (48–76)\nAsian or Pacific Islander 1,020 5.9 73 (59–83)\nAmerican Indian or Alaska \nNative90 0.5 64 (54–73)\nMultiple races 89 0.5 75 (58–84)\nUnknown 367 2.1 68 (57–78)Median age of \nhospitalization is \nlower among Black, \nHispanic, and \nAmerican \nIndian/Alaska Native \npersons than White \nand Asian/Pacific \nIslander persons. \n*Includes men and non -pregnant women.\n**Black, White, American Indian/Alaska Native and Asian/Pacific Islander people were categorized as non -Hispanic; Hispanic peopl e could be of any race.\n59\n600100200300400500\nAge 18-49 years Age 50 –59 years Age 60 –74 years Age ≥75 yearsRSV-associated hospitalizations per 100,000 \npopulationBlack\nHispanic\nWhite\nAsian & Pacific IslanderRSV-associated hospitalization rates by age group and by race \nand ethnicity, RSV -NET, 2018 –2019\nUnpublished data from RSV -NET. Rates are adjusted using multipliers for the frequency of RSV testing during each season and the sensitivity of RSV diagnostic tests. Error bars represent \n95% confidence intervals. Estimated rates exclude recorded hospitalizations among pregnant women. Black, White, and Asian/Pac ific Islander people were categorized as non -Hispanic; \nHispanic people could be of any race. Hospitalization rates among American Indian and Alaska Native persons are not shown due  to small numbers. There may be unmeasured \nconfounding, especially in the oldest age group. Although incidence appears lower in Black adults aged ≥75 years than in White adults, if Black adults are less likely to survive to age 80 or \n90 years, then differences in underlying age distribution may be driving this finding. Black adults had a \nhospitalization rate 2.3x  \nhigher than White \nadultsBlack adults had a \nhospitalization rate 1.5x  \nhigher than White adults\nBlack adults had a \nhospitalization rate 1.9x  \nhigher than White adults\n60\n61SOURCE: National Center for Health Statistics (NCHS), National Health and Nutrition Examination Survey (NHANES), 2015 –2018. All estimates are crude estimates with no age adjustment and age is age at interview. Error bars represent Korn and Graubard  95% confidence intervals. NHANES is representative of the \ncivilian, non -institutionalized U.S. population. For “narrow” definition: Severe obesity was defined as BMI ≥40 kg/m2. Diabetes with complication was defined as 1) having diabetes: self -reported diabetes, fasting plasma glucose ≥126 mg/dL, or he moglobin A1c ≥6.5%, AND 2) having one of the following complications of \ndiabetes assessed within the survey: serious heart disease as defined below, chronic kidney disease (stage 3, 4, or 5) define d as estimated glomerular filtration rate (eGFR) ˂60 (stages 3 –5) further defined below, or having self -reported diabetes and havin g a doctor previously told them that diabetes affected their eyes or \nthat they have retinopathy. Other complications of diabetes are not included in this definition. Serious heart disease was de fined based on self -report as diagnosed congestive heart failure, coronary heart disease, angina, or heart attack, or angina grades  1 or 2 determined by the Rose Angina Questionnaire. Asthma was \ndefined as self -reporting ever being diagnosed with asthma and still having asthma. Chronic kidney disease was defined as estima ted glomerular filtration rate (eGFR) ˂30 (stages 4 –5), and using a forward equation for adjustment of creatinine because of met hods changes. eGFR calculated using the 2021 CKD -EPI \ncreatinine equation (https://www.nejm.org/doi/10.1056/NEJMoa2102953). Urine albumin is not included in this definition. Chron ic obstructive pulmonary disease (COPD) was defined as self -reported diagnosed COPD, emphysema, or current chronic bronchitis. Live r condition was defined as self -reporting ever being \ndiagnosed with any kind of liver condition and still having any kind of liver condition. Having at least one of the above con ditions for the narrow definition was defined based on the seven (7) conditions listed. Among the fasting sample, ~94% had compl ete data for all reported medical conditions, ~6% were missing data \nfor one (1) medical condition, <1% were missing data for two (2) medical conditions, and none were missing data for three (3)  or more medical conditions. Estimates of having ≥1 condition are weighted using fasting sample weights. Prevalence of U.S. adults with ≥1 chronic medical condition using narrow definition of chronic \nmedical conditions* , by age and race\nNational Health and Nutrition Examination Survey (NHANES), 2015 —2018\n40.744.4\n30.439.0\n27.040.1\n15.231.8\n0102030405060708090100\nAged 50-59 Years Aged ≥ 60 Years Prevalence of at least one chronic medical condition (%)\nNon-Hispanic Black Non-Hispanic White Hispanic Non-Hispanic Asian*Narrow definition , at least one of:\n• Serious heart disease\n• Diabetes with complication\n• Chronic obstructive pulmonary disease\n• Asthma\n• Severe obesity (BMI ≥40 kg/m2)\n• Liver condition\n• Chronic kidney disease, stage 4 or 5\nBMI: body mass index\n62RSV Vaccination Coverage Among Adults Aged 60 –74 Years at Increased Risk** for Severe RSV, by \nDecember 28, 2024\nNational Immunization Survey -Adult COVID Module (NIS -ACM)\nNA: estimate not reported because denominator is <30; AI/AN: American Indian or Alaska Native; NH/OPI: Native Hawaiian or Oth er Pacific Islander; CI: 95% confidence interval; Ref: Referent category.\n*Statistically significant at p<0.05 compared to the referent category.\n**A respondent was considered to be at increased risk for severe RSV disease if they had any of the following: self -reported chr onic lung diseases, diabetes with insulin use, heart conditions, immunocompromised state, solid organ or blood stem cell \ntransplant (including bone marrow transplant), cancer, liver disease, sickle cell disease or thalassemia, or currently lives in a nursing home.\nNIS-ACM methods: Data from adults age ≥18 years are collected by telephone interview using a random -digit -dialed sample of cell telephone numbers  stratified by state, the District of Columbia, five local jurisdictions (Bexar County TX, Chicago IL, Houston TX, \nNew York City NY, and Philadelphia County PA), and Puerto Rico and the U.S. Virgin Islands. Data are weighted to represent th e non-institutionalized U.S. population and mitigate possible bias that can result from an incomplete sample frame (exclusion of \nhouseholds with no phone service or only landline telephones) or non -response. All responses are self -reported. For more informa tion about the survey, see https://www.cdc.gov/nis/about/index.html.33.625.8*35.930.433.527.1*43.732.733.529.134.9*31.4\n0 20 40 60 80 100OverallMultiple/Other, non-HispanicWhite, non-Hispanic (Ref)NH/OPI, non-HispanicHispanicBlack, non-HispanicAsian, non-HispanicAI/AN, non-HispanicMaleFemale (Ref)Rural (Ref)SuburbanUrban\nWeighted % (95% CI)NAAge 60 –74 Years, at Increased Risk (n=13,919)\n63Equity: Summary of the available evidence\nAdults 50 –59 years at increased risk of severe RSV disease \n•Overall rates of RSV among all race and ethnicity groups remain lower in adults \naged <60 years than adults 60 –74 and 75 years and older; however, Black \nadults aged 50 –59 years had higher RSV hospitalization rates than White adults\n•Chronic conditions that increase risk of severe RSV disease occur more \nfrequently among certain racial and ethnic groups aged 50 –59\n•RSV vaccine uptake varies by race and ethnicity \n64Equity\n▪What would be the impact on health equity of recommending RSV vaccination \nin adults aged 50 -59 years at increased risk of severe RSV disease?\nReduced\nProbably reduced\nProbably no impact\nProbably increased\nIncreased\nVaries\nDon’t know\nSummary\n65\n66DomainAmong adults aged 50–59 years at increased \nrisk of severe RSV diseaseWork Group Majority \nOpinion\nPublic Health \nProblemIs RSV of public health importance? Yes/Probably yes\nBenefits and \nHarmsHow substantial are the desirable anticipated effects? Moderate\nHow substantial are the undesirable anticipated effects? Small\nDo the desirable effects outweigh the undesirable effects? Favors intervention\nValuesDoes the target population feel the desirable effects are large \nrelative to the undesirable effects?Probably yes\nIs there important variability in how patients value the outcomes?Probably important uncertainty or \nvariability\nAcceptability Is the intervention acceptable to key stakeholders? Yes/Probably yes\nFeasibility Is the intervention feasible to implement? Yes/Probably yes\nResource Use Is the intervention a reasonable and efficient allocation of resources? Yes/Probably yes\nEquity What would be the impact on health equity? Probably increased\n671.ACIP recommends that adults 50 –59 years of age who are at increased \nrisk of severe RSV diseasea receive a single dose of RSV vaccine.b,cProposed ACIP vote language\na.CDC will publish Clinical Considerations that describe chronic medical conditions and other risk factors for severe \nRSV disease for use in this risk -based recommendation.\nb.RSV vaccination is recommended as a single dose only. Persons who have already received RSV vaccination are NOT \nrecommended to receive another dose. \nc.RSV vaccine can be administered with any product licensed in this age group.\n68Evidence to Recommendations Framework\nSummary: Work Group Interpretations\nBalance of \nconsequencesUndesirable \nconsequences \nclearly outweigh \ndesirable \nconsequences in \nmost settingsUndesirable \nconsequences \nprobably \noutweigh \ndesirable \nconsequences in \nmost settingsThe balance \nbetween \ndesirable and \nundesirable \nconsequences is \nclosely balanced \nor uncertainDesirable \nconsequences \nprobably \noutweigh \nundesirable \nconsequences in \nmost settingsDesirable \nconsequences \nclearly outweigh \nundesirable \nconsequences in \nmost settingsThere is \ninsufficient \nevidence to \ndetermine the \nbalance of \nconsequencesAmong adults aged 50 -59 years at increased risk of severe RSV disease:\nMinority \nopinion\n69Evidence to Recommendations Framework\nSummary: Work Group Interpretations\nIs there sufficient information to move forward with a recommendation?\nYes NoAmong adults aged 50 -59 years at increased risk of severe RSV disease:\nMinority \nopinion\n70Evidence to Recommendations Framework\nSummary: Work Group Interpretations\nWe do not recommend the intervention\nWe recommend the intervention for individuals based on shared clinical decision -making\nWe recommend the interventionType of recommendation, adults aged 50 -59 years at increased risk of \nsevere RSV disease:\n71•The Work Group also discussed which risk conditions should be included in a risk -based \nrecommendation for adults aged 50 -59 years.\n-Should risk conditions be the same as those for adults aged 60 -74 years? Or should they be different?\n•Discussion points favoring the same risk conditions as those outlined for adults aged 60 -74 years: \n-Significant concerns about complexity for providers and patients in having a different list of risk conditions for adults \naged 50 -59 years than adults aged 60 -74 years.\n-Adults aged 50 -59 years have similar conditions that increase risk of severe RSV disease as adults aged 60 -74 years.\n•Discussion points favoring a narrower list of risk conditions than those outlined for adults aged 60 -\n74 years:\n-Due to increasing vaccine fatigue and complexity of the adult immunization schedule, perhaps focus for providers \nand patients should be on a adults with a narrower list of risk conditions, who are at highest risk of severe RSV \ndisease\n-While the vaccine looks to be cost -saving for certain risk conditions, recommending RSV vaccine for the same list of \nrisk conditions among adults aged 50 -59 as 60 -74 years is less cost -effective in adults aged 50 -59 than in those 60 -\n74.\n-There remains important uncertainty in whether revaccination can restore protection to levels seen after the first \ndose. This may be a more important consideration when developing a recommendation for younger adults with \nlonger remaining life expectancy. Work Group considerations\n72•Overall, the Work Group majority feels that risk conditions for a recommendation in \nadults aged 50 -59 years should include the same conditions already outlined in the risk -\nbased recommendation for adults aged 60 -74 years\n•With this recommendation, the Work Group stresses that additional data will be critical to \nunderstand the optimal revaccination interval and that studies supporting the preferred \npolicy around revaccination are needed\n•The Work Group also stresses the importance of ongoing safety surveillance monitoringWork Group considerations\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position \nof the Centers for Disease Control and Prevention.\nAcknowledgements\n73• Adult RSV Vaccine Work Group\n• CDC Coronavirus and Other Respiratory Viruses Division\n• CDC Immunization Services Division\n• CDC Immunization Safety Office\n• National Center for Chronic Disease Prevention and Health Promotion\n• National Center for Health Statistics\n• FDA Center for Biologics Evaluation and Research\n• David Hutton, University of Michigan", "summary": "Evidence to Recommendations Framework (EtR): RSV Vaccination in Adults Aged 50 –59 years Amadea Britton, MD, Co -Lead Adult RSV Vaccine Work Group Michael Melgar, MD, Co -Lead Adult RSV Vaccine Work Group Diya Surie, MD, Co -Lead Adult RSV Vaccine Work Group Coronavirus and Other Respiratory Viruses Division (CORVD) Advisory Committee on Immunization Practices (ACIP) April 16, 2025National Center for Immunization and Respiratory Diseases 2•Should adults aged 50 –59 years at increased risk of…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/06-Melgar-Surie-adult-rsv-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 73}
{"title": "07 Surie adult RSV 508", "content": "ACIP Adult RSV Work Group Clinical Considerations\nRSV vaccination in Adults 50 –59 at increased risk of severe \nRSV diseaseDiya Surie, MD\nMichael Melgar, MD\nAmadea Britton, MD\nCo-Leads, Adult RSV Vaccine Work Group \nCoronavirus and Other Respiratory Viruses Division (CORVD)\nAdvisory Committee on Immunization Practices (ACIP)\nApril 16, 2025National Center for Immunization and Respiratory Diseases \n•Licensed products for use in adults aged 50 –59 years at increased risk of \nsevere RSV disease\n•Adults aged 50 –59 years at increased risk of severe RSV disease\n•Timing of RSV vaccination for the 2025 –2026 RSV season\n•Coadministration of RSV vaccines with other vaccinesOverview\n*Pfizer’s Abrysvo is also licensed and recommended for use in pregnancy to prevent RSV LRTD in \ninfants after birth. No other RSV vaccine should be administered in pregnancy .RSV vaccine FDA licensure for RSV prevention in adults, \nas of April 16, 2025\n20 30 40 50 60 70 80 90GSK's ArexvyPfizer's Abrysvo*Moderna's mResvia\nAge (years)18\nLicensure limited to adults at increased risk of \nRSV lower respiratory tract disease (LRTD)Licensure is for the general \npopulation of adults aged ≥60 years\n*Pfizer’s Abrysvo  is also licensed and recommended for use in pregnancy to prevent RSV LRTD in \ninfants after birth. No other RSV vaccine should be administered in pregnancy .RSV vaccine FDA licensure  for RSV prevention in adults, \nas of April 16, 2025\n20 30 40 50 60 70 80 90GSK's ArexvyPfizer's Abrysvo*Moderna's mResvia\nAge (years)18\nLicensure limited to adults at increased risk of \nRSV lower respiratory tract disease (LRTD)Licensure is for the general \npopulation of adults aged ≥60 yearsIf mResvia  gains FDA licensure in high -risk adults 50 –59, it \nwould be included in an existing recommendation by default\nAdults aged 50 –59 years at increased risk of \nsevere RSV disease\nProposed list of risk factors for the 50 –59 recommendation is \nthe same as that currently used for the 60 –74 recommendation\nNeurological or neuromuscular conditions \ncausing impaired airway clearance or \nrespiratory muscle weaknessChronic cardiovascular \ndisease\nModerate or severe \nimmunocompromise Diabetes mellitus  \ncomplicated by chronic kidney disease, \nneuropathy, retinopathy or other end -\norgan damage or requiring treatment \nwith insulin or sodium -glucose \ncotransporter -2 (SGLT2) inhibitorSevere obesity \n(body mass index \n≥40 kg/m2)Chronic lung \nor respiratory \ndisease\nEnd stage renal \ndisease/dialysis \ndependenceChronic liver \ndiseaseChronic hematologic \nconditions\nResidence in a \nnursing homeOther chronic medical conditions or risk factors that a \nprovider determines would increase risk of severe disease \ndue to viral respiratory infection (e.g., frailty) \nBritton A, Roper LE, Kotton CN, et al. Use of Respiratory Syncytial Virus Vaccines in Adults Aged ≥60 Years: Updated Recommen dations of the Advisory Committee on Immunization Practices — United States, \n2024. MMWR Morb  Mortal Wkly  Rep 2024;73:696 -702. DOI: http://dx.doi.org/10.15585/mmwr.mm7332e1 .\nIncludes information on risk of \nGuillain -Barré syndrome for the \ntwo subunit vaccines  (GSK’s \nArexvy , Pfizer’s Abrysvo )\nCurrent RSV vaccine flyer \nfor healthcare providers \nwill be updated with any \nnew recommendation\nhttps://www.cdc.gov/rsv/media/pdfs/2025/01/355818 -A_RSV_VaccineForOlderAdultsFlyer -01072025 -V9-WEB.pdf  \nGuidance on the timing of RSV vaccination is \nunchanged\n▪RSV vaccination should be given ONLY \nto adults who have not yet received a \ndose of RSV vaccine. \n▪It is anticipated that adults may need \nadditional doses of RSV vaccine in the \nfuture, but ideal revaccination timing \nis not yet known. Adults who have already received \na dose of RSV vaccine should NOT \nreceive another dose at this time. RSV vaccination will have the \nmost benefit if given in late \nsummer or early fall .\n▪This means from August to \nOctober in most of the United \nStates.\n▪Note this is not a formal seasonal \nrecommendation for RSV \nvaccination. Eligible adults may \ncontinue to receive RSV \nvaccination year -round.\nCo-administration of RSV vaccines with other \nadult vaccines\n11•With two exceptions,1,2 pre-specified non -inferiority criteria were met for \nsimultaneous vaccination, compared with separate administration.\n•The Work Group notes our limited understanding of clinical significance of \ndecreased antibody titers with RSV vaccine co -administration. ACIP previously reviewed results from studies on co -\nadministration of RSV vaccine with influenza and mRNA \nCOVID -19 vaccines\n1.Simultaneous administ ration of GSK’s Arexvy  with adjuvanted influenza vaccine resulted in lower H3N2 hemagglutination inhibition (HAI) \ntiters, compared with sequential administration. Humoral immune response against influenza A/Darwin H3N2 was also assessed po st-hoc via \nmicroneutralization, which resulted in a geometric mean titer (GMT) ratio similar to the HAI GMT ratio, with a slightly narro wer confidence \ninterval. Non -inferiority criteria were not specified for post -hoc analyses. Reference: Clark R, et al. Safety and Immunogenicit y of Respiratory \nSyncytial Virus Prefusion F Protein Vaccine when Co -administered with Adjuvanted Seasonal Quadrivalent Influenza Vaccine in Olde r Adults: A \nPhase 3 Randomized Trial. Clin Infect Dis. 2024 Oct 15;79(4):1088 -1098. https://pubmed.ncbi.nlm.nih.gov/39099085/  \n2.Simultaneous administration of Moderna’s mResvia  with high -dose influenza vaccine resulted in lower RSV -A and RSV -B neutralizing antibody \ntiters, compared with RSV vaccination alone. Reference: https://www.cdc.gov/acip/downloads/slides -2024 -10-23-24/02 -RSV-Adult -Das-\n508.pdf  \n12•Both vaccines include the same adjuvant system (AS01); adjuvant dose in \nShingrix is twice the dose in Arexvy .\n•530 immunocompetent participants aged ≥50 years were randomized 1:1 to \nreceive either sequential (control group) or simultaneous (intervention \ngroup) vaccination with Arexvy  and dose one of Shingrix, followed by \ncompletion of the Shingrix two -dose series.GSK provided results of a co -administration study with \nArexvy  and recombinant zoster vaccine (Shingrix)\nReference: Dennis P , et al. Co -administration of the adjuvanted respiratory syncytial virus (RSV) prefusion F protein vaccine (R SVPreF3 OA) with the adjuvanted \nrecombinant zoster vaccine (RZV) in adults ≥50 years of age. 20th EuGMS  Congress. 2024 Sep 18 -20; Valencia, Spain.\n13•Immunogenicity non -inferiority criteria were met (upper limit of 2 -sided \n95% CI ≤1.5 for GMT [RSV -A or RSV -B neutralization] or GMC [anti -gE] ratio; \nratio calculated as separate administration/simultaneous administration)\n-One month after Arexvy  administration, GMT ratio:\n•RSV-A neutralizing antibodies: 1.14 (95% CI: 0.97, 1.35)\n•RSV-B neutralizing antibodies: 0.98 (95% CI : 0.84, 1.15)\n-One month after dose two of Shingrix, GMC ratio:\n•Anti-gE antibodies: 1.24 (95% CI: 1.0 8, 1.42)GSK provided results of a co -administration study with \nArexvy  and recombinant zoster vaccine (Shingrix)\nCI: confidence interval, GMT: geometric mean titer, GMC: geometric mean concentration\nReference: Dennis P , et al. Co -administration of the adjuvanted respiratory syncytial virus (RSV) prefusion F protein vaccine (R SVPreF3 OA) with the adjuvanted \nrecombinant zoster vaccine (RZV) in adults ≥50 years of age. Presented at 20th EuGMS  Congress. 2024 Sep 18 -20; Valencia, Spain.\n14•No specific safety concerns identified\n•Reactogenicity of simultaneous administration overall greater than that \nof Arexvy  given alone, but more similar to that of Shingrix given alone\n•Serious adverse events: 4.9% in simultaneous administration group vs. \n2.3% in the sequential administration group, but no clustered imbalance \nin any specific organ system or type of adverse event\n•No cases of Guillain -Barr é syndrome (GBS) or acute disseminated \nencephalomyelitis (ADEM)*GSK provided results of a co -administration study with \nArexvy  and recombinant zoster vaccine (Shingrix)\n*With total enrollment of 530 participants, this trial was underpowered to detect rare adverse events.\nReference: Dennis P , et al. Co -administration of the adjuvanted respiratory syncytial virus (RSV) prefusion F protein vaccine (R SVPreF3 OA) with the adjuvanted \nrecombinant zoster vaccine (RZV) in adults ≥50 years of age. 20th EuGMS  Congress. 2024 Sep 18 -20; Valencia, Spain.\n15•Co-administration of RSV vaccines and other recommended adult vaccines \nis common.\n•Given the considerable benefits of co -administration and the evidence of \nsafety of co -administration, the Work Group continues to feel co -\nadministration is acceptable .1 \n•In addition, the Work Group looks forward to learning more about an \nanalysis by Moderna on immunologic correlates of protection for RSV when \npeer -reviewed publication is available.Work Group interpretations of co -administration data\n1.This language is different from CDC’s General Best Practices Guidelines for Immunization, which states that with limited exce ption, \nroutine administration of all age -appropriate doses of vaccines simultaneously is recommended for persons for whom no specific \ncontraindications exist at the time of the visit.\nKroger A, Bahta  L, Long S, Sanchez P . General Best Practice Guidelines for Immunization. Best Practices Guidance of the Advisory Committee on  \nImmunization Practices (ACIP). https://www.cdc.gov/vaccines/hcp/imz -best -practices/ . Updated July 22, 2024; accessed October 22, 2024\n16•Whether the patient is up to date with currently recommended vaccines\n•The feasibility of the patient returning for additional vaccine doses\n•Risk of acquiring vaccine -preventable disease\n•Vaccine reactogenicity profiles\n•Patient preferencesWhen deciding whether to co -administer other vaccines \nwith an RSV vaccine, providers may consider: \nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position \nof the Centers for Disease Control and Prevention.\nAcknowledgements\n• Adult RSV Vaccine Work Group\n• CDC Coronavirus and Other Respiratory Viruses Division\n• CDC Immunization Services Division", "summary": "ACIP Adult RSV Work Group Clinical Considerations RSV vaccination in Adults 50 –59 at increased risk of severe  RSV diseaseDiya Surie, MD Michael Melgar, MD Amadea Britton, MD Co-Leads, Adult RSV Vaccine Work Group  Coronavirus and Other Respiratory Viruses Division (CORVD) Advisory Committee on Immunization Practices (ACIP) April 16, 2025National Center for Immunization and Respiratory Diseases  •Licensed products for use in adults aged 50 –59 years at increased risk of  severe RSV disease…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/07-Surie-adult-RSV-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 17}
{"title": "01 Asturias chikungunya 508", "content": "CHIKUNGUNYA VACCINES\nACIP Meeting\nApril 16, 2025\nEdwin Asturias, MD\nChair, ACIP Chikungunya Vaccines Work Group\n•Chikungunya Vaccines Work Group formed in May 2022\n-Topics under discussion include use of chikungunya vaccines in U.S. persons at \nrisk of chikungunya, including those who travel abroad, laboratory workers, and \nresidents of U.S. territories and states at risk of transmission\n•Two chikungunya vaccines \n-Live attenuated vaccine licensed in November 2023 (manufactured by Valneva)\n-Virus -like particle vaccine licensed in February 2025 (manufactured by Bavarian \nNordic)\n-Both vaccines licensed based on immunogenicity correlates and safety, pending \nclinical efficacy and expanded safety post -licensure studiesBackground\n•October 2022– October 2023\n-Background on chikungunya disease and its epidemiology\n-Immunogenicity and safety of live attenuated chikungunya vaccine (CHIK -LA)\n•February 2024\n-ACIP approval of recommendations for use of CHIK -LA among U.S. travelers and \nlaboratory workers\n•June 2024\n-Epidemiology of chikungunya in U.S. territories and states\n-Cost -effectiveness of use of CHIK -LA in U.S. territories \n•October 2024\n-Immunogenicity and safety of virus -like particle chikungunya vaccine (CHIK -VLP)Recap of previous Work Group ACIP presentations\n1. Evidence to Recommendations for use of CHIK -VLP among adolescent \nand adult travelers ( Vote 1 )\n2. Evidence to Recommendations for use of CHIK -VLP among laboratory \nworkers ( Vote 2 ) \n3. Surveillance for adverse events following use of CHIK -LA and proposed \nguidance for use and revised recommendations (Vote 3 )  \n4. Clinical guidance for use of CHIK -VLP among pregnant and breastfeeding \nwomenOverview of today’s session\nChikungunya Vaccines Work Group members\nACIP ACIP Liaisons Invited Consultants ( cont )\nEdwin Asturias, Univ Colorado Elizabeth Barnett, ISTM Steven Schofield, CATMAT\nLin Chen, Mount Auburn Hosp James Campbell, AAP David Shlim, Jackson Hole Travel & Trop Med\nMary Pat Friedlander, AAFP Nestor Sosa, Uni New Mexico Hospital\nCDC Lead Saroj Rai, AIM Sanet Torres, San Jorge Children & Women's Hospital\nSusan Hills, DVBD Kirsten Vannice, Bill & Melinda Gates Foundation\nInvited Consultants Mary Wilson, Univ California San Francisco\nEx Officio Alan Barrett, Univ Texas Galveston Joshua Wong, US Coast Guard Puerto Rico\nRobin Levis, FDA Beth Bell, Univ Washington\nSixun Yang, FDA Alan Lam, DoD\nLesley Dupuy (NIH) Margaret Ryan, DoD\nChikungunya Vaccines Work Group CDC participants\nDVBD DGMH ACIP Secretariat (NCIRD)\nSarah Guagliardo Kevin O’Laughlin Jessica MacNeil\nAnn Powers Leslie Lee\nErin Staples DHQP\nParker Acevedo Michael McNeil\nLaura Adams\nGID\nNCEZID Pierre Muhoza\nChris Braden", "summary": "CHIKUNGUNYA VACCINES ACIP Meeting April 16, 2025 Edwin Asturias, MD Chair, ACIP Chikungunya Vaccines Work Group •Chikungunya Vaccines Work Group formed in May 2022 -Topics under discussion include use of chikungunya vaccines in U.S. persons at  risk of chikungunya, including those who travel abroad, laboratory workers, and  residents of U.S. territories and states at risk of transmission •Two chikungunya vaccines  -Live attenuated vaccine licensed in November 2023 (manufactured by Valneva)…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/01-Asturias-chikungunya-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 6}
{"title": "02 Hills chikungunya 508", "content": "Evidence to Recommendations and proposed \nrecommendations for use of virus -like particle \nchikungunya vaccine among adolescent and adult travelers\nDr Susan Hills\nCDC Lead, ACIP Chikungunya Vaccines Work GroupNational Center for Emerging and Zoonotic Infectious Diseases\nApril 16 , 2025\nVirus- like particle chikungunya vaccine \n(CHIK -VLP) and its licensure\n•Manufactured by Bavarian Nordic (trade name: VIMKUNYA\n )\n•Licensed in United States on February 14, 2025\n•Indicated for use in persons aged ≥12 years\n•Single dose primary schedule CHIK -VLP\n\nLicensure\n•Licensed through Accelerated Approval pathway used for products for \nserious conditions and that fill unmet medical need\n-Traditional approval challenging as efficacy trial difficult when outbreaks unpredictable \nand duration can be short, and no established immunologic correlate of protection\n•Effectiveness demonstrated based on adequate and well -controlled trials \nshowing vaccine has effect on surrogate endpoint reasonably likely to \npredict clinical benefit\n-CHIK -VLP surrogate was chikungunya neutralizing antibody titer threshold preventing \nviremia in non -human primates challenged with virus\n•Regardless of licensure pathway, safety must be assessed in adequate \nand well -controlled studies with appropriate safety sample size\nPost -marketing study\n•Under FDA regulations, post -marketing clinical trial required to confirm \nclinical benefit \n•Randomized, double -blind, placebo -controlled study planned to evaluate \nefficacy, safety, and immunogenicity of CHIK -VLP\nEvidence to Recommendations for use of \nCHIK -VLP among travelers aged ≥12 years\nShould CHIK- VLP be recommended for use in persons aged \n≥12 years traveling to areas with risk of chikungunya virus \ntransmission?Policy question\nEtR framework\nEtR Domain Question\nPublic health problem •Is the problem (chikungunya) of public health importance?\nBenefits and harms•How substantial are the desirable anticipated  effects of CHIK -VLP?\n•How substantial are the undesirable anticipated  effects?\n•Do the desirable effects outweigh the undesirable  effects?\n•What is the overall certainty of this evidence for the critical outcomes? \nValues•Does the target population feel the desirable effects are large relative to \nthe undesirable effects?\n•Is there important variability in how patients value theoutcomes?\nAcceptability •Is the intervention acceptable to keystakeholders?\nResource use •Is the intervention a reasonable and efficient allocation ofresources?\nEquity •What would be the impact of the intervention on health equity?\nFeasibility •Is the intervention feasible to implement?\nDomain 1: Public Health Problem\nChikungunya virus transmission\nCountries and territories with current or past transmission of chikungunya virus\n\nGlobally, ~620,000 cases \nreported in 2024 but likely \nunderestimate\nCountries and territories with current or past transmission of chikungunya virusChikungunya virus disease cases\n Outbreaks can be   \nlarge and explosive\n•One-third to three -\nquarters of po pulation  \naffected\n•Substantial morbidity\n•Stresses healthcare \ncapacity\n•Fever and polyarthralgia\n-Arthralgia often severe and can be \ndebilitating\n-Multiple joints involved, most \ncommonly hands and feet\n•Other symptoms include \nheadache, myalgia, fatigue, rash, \nabdominal pain, and vomiting\n•No anti -viral treatment\n-Supportive managementImpact of acute illness\nImage above from : https://www.paho.org/en/topics/chikungunya\nImpact of disease: severe presentations \n•Cases of severe illness uncommon\n-Infection -related  (e.g., encephalitis, \nmyocarditis )\n-Exacerbation of underlying medical \nconditions\n•Rare deaths \n-Case fatality rate: 0.01% –0.5% \n-Mostly in older adults , particularly \nthose with comorbidities, and young \ninfants  infected through intrapartum \ntransmission or by mosquito bites\nImages from : https://www.paho.org/en/topics/chikungunya\nImpact of disease: Arthralgia that persists or recurs\n•Most patients have arthralgia that resolves in 7 –10 days\n•Arthralgia sometimes persists or relapses with other symptoms e.g., \nfatigue\n•Rates of ongoing arthralgia vary based on several factors e.g., severity of \nacute illness, age, pre -existing joint problems\nImpact of disease: Arthralgia that persists or recurs\n51% 3 months\npost -infectionAcute \nillness\n100% \nBased on recent meta -analysis (Lindsey N. Chronic arthralgia after chikungunya. US Advisory Committee on Immunization Practices meeting, June 2023)*\nImpact of disease: Arthralgia that persists or recurs\nBased on recent meta -analysis (Lindsey N. Chronic arthralgia after chikungunya. US Advisory Committee on Immunization Practices meeting, June 2023)*\n*Rates likely overestimated as background rate of arthralgia in the population could not be taken into account51% 3 months\npost -infection12 months\npost -infection\n38%Acute \nillness\n100% \n•Risk highly variable from location -to-location and from year -to-year\n•2014– 2015: High case load during outbreak in the Americas\n•2022– 2024: 100– 200 US traveler cases/year although extent of underdiagnosis and \nunderreporting unknownIs chikungunya a problem of public health importance for \nUS travelers? \nChikungunya cases in US travelers reported to CDC, 2012– 2024 (N=5,012)* \n*2024 data are provisional\n\nComparison of chikungunya  vs. dengue  cases among travelers\nExcept during 2014– 2015, 3–18 times fewer  chikungunya  cases reported annually as dengue  cases\n\nChikungunya risk estimates for travelers for 1 week  \ntravel to outbreak  or non- outbreak  area*  \n•Travelers to outbreak  area for 1 week\n-Clinical disease: 667 cases per 100,000\n-Hospitalization: 27 cases per 100,000\n-Chronic arthralgia of any severity at 12 months: 253 cases per 100,000 \n*Based on unpublished data gathered during outbreaks in Puerto Rico and United States Virgin Islands with potential limitatio ns and calculations requiring assumptions\n•Travelers to outbreak  area for 1 week\n-Clinical disease: 667 cases per 100,000\n-Hospitalization: 27 cases per 100,000\n-Chronic arthralgia of any severity at 12 months: 253 cases per 100,000 \n•Travelers to non-outbreak  area for 1 week \n-Clinical disease: 6.7 cases per 100,000 \n-Hospitalization : 0.3 cases per 100,000 \n-Chronic arthralgia of any severity at 12 months: 2.5 cases per 100,000\n*Based on unpublished data gathered during outbreaks in Puerto Rico and United States Virgin Islands with potential limitatio ns and calculations requiring assumptionsChikungunya risk estimates for travelers for 1 week  \ntravel to outbreak  or non- outbreak  area*  \n•Travelers visiting non-outbreak  area for 1 week  \n-Clinical disease: 6.7 cases per 100,000 \n-Hospitalization : 0.3 cases per 100,000 \n-Chronic arthralgia of any severity at 12 months: 2.5 cases per 100,000\n•Travelers visiting non-outbreak  area for 6 months\n-Clinical disease: 176 cases per 100,000\n-Hospitalization : 7 cases per 100,000\n-Chronic arthralgia of any severity at 12 months: 67 cases per 100,000\n*Based on unpublished data gathered during outbreaks in Puerto Rico and United States Virgin Islands with potential limitatio ns and calculations requiring assumptionsChikungunya risk estimates for travelers to non- outbreak  \narea for 1 week  or 6 months*  \nQuestion: Is chikungunya of public health importance?\n•For US travelers\n-Most important factor is level of \nchikungunya virus transmission at  \ndestination\n-Additional factors are travel duration \nand other considerations (e.g., age, \nunderlying medical conditions)□No\n□Probably no\n□Probably yes\n□Yes\n□Varies\n□Don’t know\nDomain 2: Benefits and Harms of CHIK -VLP\nDesirable  anticipated effects of vaccination \nCritical GRADE outcomes Comment\nShort -term vaccine efficacy (i.e., at 21 days) \nagainst diseaseImmunogenicity data only\nLong -term vaccine efficacy (i.e., at 12 months) \nagainst diseaseImmunogenicity data only\n•No established immunologic correlate of protection\n-Surrogate marker of protection based on neutralizing antibody titer estimated from \nvalidated non- human primate model\nSeroresponse rate at 21 days after vaccination* \n•Key results from two randomized controlled trials\n-Adolescents and adults aged 12 –64 years (N= 2,559 subjects with results in \nvaccine arm)\n-Older adults aged ≥65 years (N=189 subjects with results in vaccine arm)\n•Seroresponse  rate 97% overall\n-98% in ages 12– 64 years vs. 87% in ages ≥65 years \n*Percent of subjects with anti -chikungunya virus 80% serum neutralizing antibody titer ≥100 \nSeroresponse rate at 12 months after vaccination* \n•Long -term results from Phase 3 study not yet available\n•Results from one Phase 2 study with data collection at 11 months\n-Adults aged 18 –45 years (N=46 subjects with results)\n-Seroresponse rate 91%\n•Given limited data, also reviewed Phase 3 study results at 6 months\n-Adolescents and adults aged 12 –64 years: seroresponse rate 85% (1967/2301)\n-Older adults aged ≥65 years: seroresponse rate 76% (139/184)\n*Percent of subjects with anti -chikungunya virus 80% serum neutralizing antibody titer ≥100 \nQuestion: How substantial are the desirable  anticipated \neffects?\n□Minimal\n□Small\n□Moderate\n□Large\n□Varies\n□Don’t know\nUndesirable  anticipated effects of vaccination \nCritical outcomes\nSerious adverse events (SAEs) All SAEs and related SAEs\nArthralgia/arthritisAll arthralgia, severe arthralgia, persistent \narthralgia, and arthritis\nSAEs within 6 months\n•SAE\n-0.9% (27 of 2,996) vaccinated subjects in 2 randomized trials\n-0.6% (4 of 671) placebo recipients*\n•Related SAE \n-1 event (0.03%) considered possibly vaccine -related by site investigator\n•Retinal detachment in subject with history of seeing black spots in same \neye 1 month pre -study#\n*Not significantly different;   #Considered unrelated by Safety Monitoring Committee Chair \nArthralgia and arthritis after vaccination\n•Results from 3 randomized studies\n•Arthralgia within 7 days\n-7% (221 of 3,019) vaccinated vs. 6% (52 of 866) placebo recipients*\n•Severe arthralgia# within 7 days\n-0.2%  (7 of 3,019) vaccinated vs. 0.2%  (2 of 866) placebo recipients*\n•Persistent arthralgia commencing within 7 days and with duration >15 days\n-0.03%  (1 of 3,019) vaccinated vs. 0% (0 of 866) placebo recipients*\n•Arthritis within 28 days \n-0.03%  (1 of 3,048) vaccinated vs. 0% (0 of 723) placebo recipients*\n*Not significantly different; #Event that prevented daily activity in accordance with US FDA toxicity grading scale\n \nQuestion: How substantial are the undesirable  \nanticipated effects?\n•Rates of SAEs and all arthralgia/arthritis \noutcomes not significantly different in vaccine and placebo groups\n•Unclear determination of relatedness \nfor SAE reported as related□Minimal\n□Small\n□Moderate\n□Large\n□Varies\n□Don’t know\nDo the desirable effects outweigh the undesirable \neffects?\nVery good short -term seroresponse  rates and similar \nrates of adverse events in vaccine and placebo groups\nCan prevent acute illness that can be severe, rare \nserious complications, and long -term arthralgia \nPossibility of rare SAEs; with safety results from ~3,000 \nsubjects, post -marketing safety surveillance important\nDo the desirable effects outweigh the undesirable \neffects?\n□Favors intervention\n□Favors comparison\n□Favors both\n□Favors neither\n□Varies\n□Don’t know•Risk varies substantially and inversely \nwith chikungunya virus transmission intensity\n•Risk-benefit assessment favorable if \nvaccine used in line with proposed recommendations which target higher risk travelers\nOverall certainty of evidence from GRADE analysis for \ncritical outcome of prevention of disease  \nCritical outcome Certainty \nof evidenceRationale\nShort -term vaccine \nefficacy at 21 daysLow Downgraded for very serious indirectness\n•No effectiveness data, immunogenicity data used\n•No established immunologic correlate of protection\n•Surrogate endpoint approved for licensure has FDA \nrequirement for post -licensure controlled trials to \nconfirm clinical benefit\nOverall certainty of evidence from GRADE analysis for \ncritical outcome of prevention of disease  \nCritical outcome Certainty \nof evidenceRationale\nShort -term vaccine \nefficacy at 21 daysLow Downgraded for very serious indirectness\n•No effectiveness data, immunogenicity data used\n•No established immunologic correlate of protection\n•Surrogate endpoint approved for licensure has FDA \nrequirement for post -licensure controlled trials to \nconfirm clinical benefit\nLong -term vaccine \nefficacy at 12 monthsVery low Downgraded for very serious indirectness and imprecision•Indirectness factors as above\n•Results from Phase 3 trial not yet available so used \ndata from Phase 2 study (N=46 subjects with results) \nsupplemented by Phase 3 studies 6 -month data \nOverall certainty of evidence from GRADE analysis for \ncritical outcome of prevention of disease  \nCritical outcome Certainty \nof evidenceRationale\nShort -term vaccine \nefficacy at 21 daysLow Downgraded for very serious indirectness\n•No effectiveness data, immunogenicity data used\n•No established immunologic correlate of protection\n•Surrogate endpoint approved for licensure has FDA \nrequirement for post -licensure controlled trials to \nconfirm clinical benefit\nLong -term vaccine \nefficacy at 12 monthsVery low Downgraded for very serious indirectness and imprecision•Indirectness factors as above\n•Results from Phase 3 trial not yet available so used \ndata from Phase 2 study (N=46 subjects with results) \nsupplemented by Phase 3 studies 6 -month data \nGRADE summary of certainty: Low (short -term) and very low (long -term)\nSummary statements on short - and long - term \nprevention of chikungunya by CHIK -VLP\n•For short -term disease prevention, based on large effect and low certainty \nin the evidence \n-CHIK -VLP might result in large increase in short -term protection against \nchikungunya \n•For long -term disease prevention, based on large effect and very low \ncertainty in the evidence\n-CHIK -VLP might result in large increase in long -term protection against \nchikungunya but the evidence is very uncertain \nCritical outcome Certainty \nof evidenceRationale\nAny or related SAEs Low Downgraded for very serious imprecision\n•Fragility of estimate as sample size insufficient to \ndetect rare events\n•95% confidence intervals (CI) for effect estimates include potential for possible benefits or harmsOverall certainty of evidence from GRADE analysis for \ncritical outcome of potential adverse events  \nCritical outcome Certainty \nof evidenceRationale\nAny or related SAEs Low Downgraded for very serious imprecision\n•Fragility of estimate as sample size insufficient to \ndetect rare events\n•95% confidence intervals (CI) for effect estimates include potential for possible benefits or harms\nAny, severe, or \npersistent arthralgia, or \narthritisModerate Downgraded for serious imprecision\n•95% CI for effect estimate includes potential for \npossible benefits or harms (arthralgia)\n•Fragility of estimate as sample size insufficient to \ndetect rare events (severe or persistent arthralgia, \narthritis)Overall certainty of evidence from GRADE analysis for \ncritical outcome of potential adverse events  \nCritical outcome Certainty \nof evidenceRationale\nAny or related SAEs Low Downgraded for very serious imprecision\n•Fragility of estimate as sample size insufficient to \ndetect rare events\n•95% confidence intervals (CI) for effect estimates include potential for possible benefits or harms\nAny, severe, or \npersistent arthralgia, or \narthritisModerate Downgraded for serious imprecision\n•95% CI for effect estimate includes potential for \npossible benefits or harms (arthralgia)\n•Fragility of estimate as sample size insufficient to \ndetect rare events (severe or persistent arthralgia, \narthritis)\nGRADE summary of certainty: Low (based on outcome with lowest certainty level)Overall certainty of evidence from GRADE analysis for \ncritical outcome of potential adverse events  \nSummary statements on safety of CHIK -VLP\n•For SAEs and related SAEs, based on small but important effect and low \ncertainty in the evidence \n-CHIK -VLP might result in slight increase in SAEs and related SAEs when compared \nwith placebo \n•For arthralgia/arthritis outcomes, based on no effect and moderate certainty in the evidence \n-CHIK -VLP probably results in little to no difference in arthralgia, severe arthralgia, \npersistent arthralgia, and arthritis after vaccination compared with placebo  \nDomain 3: Values and Preferences\nPerceptions of US adults aged ≥18 years of chikungunya \ndisease and value of chikungunya vaccination \n•Online CDC survey conducted in 2022 \n•Participants provided information on \n-Risk for disease with travel during outbreak or non -outbreak periods\n-Rates of chronic arthralgia after chikungunya\n-Vaccine cost \nN=4,14642%\n26%32%\nLikely* Unsure Unlikely**Perceptions of US adults aged ≥18 years of chikungunya \ndisease and value of chikungunya vaccination \nOutbreak (disease risk of 1 in 150)\n*Includes very and somewhat likely responses\n**Includes very and somewhat unlikely responses\nN=4,146 N=4,13842%\n26%32%\nLikely* Unsure Unlikely**27%\n24%49%\nLikely* Unsure Unlikely**Perceptions of US adults aged ≥18 years of chikungunya \ndisease and value of chikungunya vaccination \nOutbreak (disease risk of 1 in 150) Non -outbreak (disease risk of 1 in 15,000)\n*Includes very and somewhat likely responses\n**Includes very and somewhat unlikely responses\nVariability in responses\n•Lower likelihood of vaccination\n-Persons aged 18 –29 years\n-Lower education\n-Lower household income\n-Black race\nImportant factors in decision -making\nRisk of disease\nVaccine side effects Avoiding long -term joint pain Vaccine cost\nQuestion: Does the target population feel that the \ndesirable effects of vaccination are large relative to undesirable effects? \n•Level of disease risk key factor in \ndetermining likelihood of vaccination□No\n□Probably no\n□Probably yes\n□Yes\n□Varies\n□Don’t know\nQuestion: Is there important uncertainty about or \nvariability in how much people value the main outcomes?\n□Important uncertainty or variability\n□Probably not important uncertainty \nor variability\n□No important uncertainty or variability\n□No known undesirable outcomes\nDomain 4: Acceptability\nAcceptability to key stakeholders\n•Travel medicine and other healthcare providers \n-Vaccine is tool for disease prevention in addition to guidance for \nmosquito bite prevention measures  \n•Travelers\n-Vaccine provides option to protect from disease that can cause severe acute illness and potentially long -term joint pain \n-Vaccine recommendations might allow insurance coverage\nQuestion: Is the intervention acceptable to key \nstakeholders?\n□No\n□Probably no\n□Probably yes\n□Yes\n□Varies\n□Don’t know\nDomain 5: Resource Use\nResource use considerations\n•Cost -effectiveness analysis for chikungunya vaccination of travelers has not been \npublished \n•Past analyses conducted for travel vaccines indicate most travel vaccines are not \ncost-effective\n–Number of travelers needed to be vaccinated to prevent one case often high\n•Resource use considerations less relevant for travel vaccine as not paid for by public \nfunding\n•Travelers make individual decisions based on their willingness to pay and \nperceptions and tolerance of risk\nQuestion: Is the intervention a reasonable and efficient \nallocation of resources? \n•Vaccine recommendations targeted to \nhigher risk travelers so financial \nimplications of vaccine purchase and \nmost benefit will be for travelers at \nhighest risk of disease □No\n□Probably no\n□Probably yes\n□Yes\n□Varies\n□Don’t know\nDomain 6: Equity\nHealth equity considerations \n•Vaccine paid for out of pocket by most travelers\n-Some travelers will have financial means to allow vaccination and others \nwill not\nQuestion: What would the impact be on health equity? \n•Chikungunya vaccine \nrecommendations cannot address this issue□Reduced\n□Probably reduced\n□Probably no impact\n□Probably increased\n□Increased\n□Varies \n□Don’t know\nDomain 7: Feasibility\nFeasibility considerations \n•Easy to administer in healthcare setting because of single dose primary schedule\n•Resources to guide implementation will be available on CDC website, including \ninformation on areas with outbreaks and with elevated risk for US travelers\n-Possible challenge is need to regularly refer to website for current  information\n•Delays in recognizing outbreaks could impact implementation of outbreak \nrecommendation and put travelers at risk\n-Risk-benefit assessment does not favor vaccinating all travelers to address this issue\n•Potential challenges with availability of two chikungunya vaccines with some different \nindications for use, so clear information will be needed  \nQuestion: Is the option feasible to implement? \n□No\n□Probably no\n□Probably yes\n□Yes\n□Varies\n□Don’t know\nBalance of consequences\no Undesirable \nconsequences clearly outweigh desirable consequences in most settingso Undesirable consequences probably outweigh desirable consequences in most settingso The balance between desirable and undesirable consequences is closely balanced or uncertaino Desirable \nconsequences \nprobably \noutweigh \nundesirable \nconsequences \nin most settingso Desirable \nconsequences clearly outweigh undesirable consequences in most settingso There is insufficient evidence to determine the balance of consequences\nDraft recommendations for CHIK -VLP for \nACIP’s consideration\nAcknowledgment of ACIP Chikungunya Vaccines Work Group \nmembers’ hard work and decision -making challenges for \nfinalizing vaccine recommendations\nACIP recommends  virus -like particle chikungunya vaccine for persons aged \n≥12 years traveling to a country or territory where there is a chikungunya \noutbreak.#\nIn addition, virus -like particle chikungunya vaccine may be considered  for \npersons aged ≥12 years traveling or taking up residence in a country or \nterritory without an outbreak but with elevated risk for US travelers# if \nplanning travel for an extended period of time e.g., 6 months or more.Draft recommendations for CHIK -VLP\n#Resources will be available on CDC website\nSpecifying areas with outbreaks and risk for US travelers \nfor purposes of recommendations\n•Outbreak  \n-Defined as occurring when CDC posts information on outbreak on CDC website\n•Country or territory without an outbreak but with elevated risk for US \ntravelers\n-Median of ≥1 US traveler case during last 5 years with at least 1 confirmed case \nbased on molecular testing or presence of IgM and neutralizing antibodies*\n*Excludes probable cases with IgM antibodies alone because high proportion are false positive results\nACIP recommends  virus -like particle chikungunya vaccine for persons aged \n≥12 years traveling to a country or territory where there is a chikungunya \noutbreak.\nIn addition, virus -like particle chikungunya vaccine may be considered  for \npersons aged ≥12 years traveling or taking up residence in a country or \nterritory without an outbreak but with elevated risk for US travelers if \nplanning travel for an extended period of time e.g., 6 months or more.Draft recommendations for CHIK -VLP\nACIP Chikungunya Vaccines Work Group\nArboviral Diseases Branch, CDC\n•Erin StaplesAcknowledgments\nFor more information, contact CDC\n1-800- CDC- INFO (232 -4636)\nTTY:  1 -888- 232- 6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.", "summary": "Evidence to Recommendations and proposed  recommendations for use of virus -like particle  chikungunya vaccine among adolescent and adult travelers Dr Susan Hills CDC Lead, ACIP Chikungunya Vaccines Work GroupNational Center for Emerging and Zoonotic Infectious Diseases April 16 , 2025 Virus- like particle chikungunya vaccine  (CHIK -VLP) and its licensure •Manufactured by Bavarian Nordic (trade name: VIMKUNYA  ) •Licensed in United States on February 14, 2025 •Indicated for use in persons…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/02-Hills-chikungunya-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 70}
{"title": "03 staples chikungunya 508", "content": "Evidence to Recommendations and proposed \nrecommendations for use of virus -like particle \nchikungunya vaccine among laboratory workers\nDr J. Erin Staples\nArboviral Diseases Branch\nCenters for Disease Control and PreventionNational Center for Emerging and Zoonotic Infectious Diseases\nApril 16 , 2025\nInfections among laboratory workers \n•At least 44 chikungunya virus infections identified among laboratory \nworkers worldwide over ~50 years1–3\n-43 cases overt disease, 1 asymptomatic infection, no deaths\n•4 disease cases in US laboratorians since chikungunya became notifiable disease in 2015\n•Identified cases underestimate all infections as no formal laboratory surveillance system\n1. The Subcommittee on Arbovirus Laboratory Safety of the American Committee on Arthropod -Borne Viruses. Am J Trop Med Hyg  1980;\n2. Rusnak JM, et al. J Occup Environ Med 2004; 3. US national arboviral disease surveillance system, 2015– 2024 \nRoutes of transmission in the laboratory\n•Aerosol\n•Percutaneous\n-Needlestick while working with and \ninjecting mice\n-Forceps prick while dissecting mosquitoes infected with chikungunya virus\n•Mucosal (possible) \n\n•Three main genotypes of chikungunya virus (Asian, West African, and \nEast/Central/South African [ECSA]) \n-CHIK -VLP based on West African genotype virus, most genetically distinct \n-Chikungunya virus strains generally considered to constitute single serotype\n•Non -human primates (NHPs) immunized with virus -like particles were protected \nfrom challenge with ECSA chikungunya virus strain1\n-No NHP challenge studies with Asian genotype virus strain\n•Sera from vaccinated persons showed neutralization of all genotypes2,3  \n-Some variability in neutralizing antibody titers between lineages\n•CHIK -VLP will likely cross -protect against all virus strains but not provenCross- protection against different chikungunya virus genotypes \nby chikungunya virus -like particle vaccine (CHIK -VLP)\n1. Akahata W et al, Nat Med 2010. 2. Goo et al, J Infect Dis 2016. 3. Chang LJ et al, Lancet 2014. \nShould chikungunya virus -like particle vaccine be recommended for \nlaboratory staff at risk for chikungunya virus infection?Policy question\nDomain: Public Health Problem\nTopic Decision Considerations\nPublic health \nproblemNo, not of public health importance overall•Only occasional laboratory -acquired \ninfections reported in United States\n•For laboratorians potential exists for acute infection with severe polyarthralgia and possible chronic arthralgia\nDomain: Benefits and Harms*\nTopic Decision Considerations\nBenefits and \nHarmsDesirable anticipated effects of vaccination are moderate•Very good short -term seroresponse  rates\n•Limited long -term seroresponse  data; \nsustained protection important for staff if work in laboratory for many years\n•CHIK -VLP likely protects against all \nchikungunya virus genotypes but not proven\nUndesirable anticipated effects of vaccination are small•Rates of serious adverse events and all arthralgia/arthritis outcomes not significantly different between vaccinated and placebo groups in clinical trials\n*Based on GRADE assessment\nDomain: Benefits and Harms*\nTopic Decision Considerations\nBenefits and \nHarmsDesirable effects outweigh the undesirable effects (favors intervention)•Acceptable immunogenicity and safety results from clinical trials\n•Prevention of potentially severe illness\nCertainty of evidence for \nprevention of disease: Low \n(short -term efficacy) and very \nlow (long -term efficacy)\nCertainty of evidence for \npotential adverse events: Low•Review of clinical trial data in GRADE \nassessment\n*Based on GRADE assessment\nDomain: Values\nTopic Decision Considerations\nValues Laboratorians likely think \ndesirable effects large relative to \nundesirable effects \nNo important variability•Scientists understand risks of disease and \nrisks and benefits of vaccination\nAcceptability Yes, acceptable to key stakeholders•Acceptable for occupational health \ndirectors, laboratory managers, and \nlaboratorians because will improve safety\nDomain: Acceptability\nTopic Decision Considerations\nValues Laboratorians likely think \ndesirable effects large relative to \nundesirable effects \nNo important variability•Scientists understand risks of disease and \nrisks and benefits of vaccination\nAcceptability Yes, acceptable to key stakeholders•Acceptable for occupational health \ndirectors, laboratory managers, and \nlaboratorians because will improve safety\nDomain: Resource Use\nTopic Decision Considerations\nResource use Yes, reasonable and efficient \nallocation of resources•Vaccination for limited number of staff undertaking research or specific diagnostic work with chikungunya virus\n•Small cost to avoid impact and costs of worker becoming infected\nEquity Probably increased •If employer offers vaccination, will improve safety for staff and addresses an \noccupational health issue\nFeasibility Yes, feasible •Likely incorporated into existing \noccupational health program\nDomain: Equity\nTopic Decision Considerations\nResource use Yes, reasonable and efficient \nallocation of resources•Vaccination for limited number of staff undertaking research or specific diagnostic work with chikungunya virus\n•Small cost to avoid impact and costs of worker becoming infected\nEquity Probably increased •If employer offers vaccination, will improve safety for staff and addresses an \noccupational health issue\nFeasibility Yes, feasible •Likely incorporated into existing \noccupational health program\nDomain: Feasibility\nTopic Decision Considerations\nResource use Yes, reasonable and efficient \nallocation of resources•Vaccination for limited number of staff undertaking research or specific diagnostic work with chikungunya virus\n•Small cost to avoid impact and costs of worker becoming infected\nEquity Probably increased •If employer offers vaccination, will improve safety for staff and addresses an \noccupational health issue\nFeasibility Yes, feasible •Likely incorporated into existing \noccupational health program\nBalance of consequences for CHIK- VLP vaccination of \nlaboratory workers at risk for chikungunya virus infection\no Undesirable \nconsequences clearly outweigh desirable consequences in most settingso Undesirable consequences probably outweigh desirable consequences in most settingso The balance between desirable and undesirable consequences is closely balanced or uncertaino Desirable \nconsequences \nprobably \noutweigh \nundesirable \nconsequences \nin most settingso Desirable \nconsequences clearly outweigh undesirable consequences in most settingso There is insufficient evidence to determine the balance of consequences\nACIP recommends virus- like particle chikungunya vaccine for laboratory \nworkers with potential for exposure to chikungunya virus.*Draft recommendation for CHIK -VLP vaccination for \nlaboratory workers\n*Consistent with language of recommendation for vaccination of laboratory workers with live attenuated \nchikungunya vaccine approved by ACIP in February 2024\n•Local biosafety committee should undertake risk assessment of potential \nfor chikungunya virus exposure considering \n-Type of work to be performed \n-Biosafety level at which work is being conducted\n•Vaccination not necessary for workers handling routine clinical samples Information accompanying recommendations\nACIP recommends virus- like particle chikungunya vaccine for laboratory \nworkers with potential for exposure to chikungunya virus.Draft recommendation for CHIK -VLP vaccination for \nlaboratory workers\nACIP Chikungunya Vaccines Work Group\nArboviral Diseases Branch, CDC\n•Susan HillsAcknowledgments\nFor more information, contact CDC\n1-800- CDC- INFO (232 -4636)\nTTY:  1 -888- 232- 6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.", "summary": "Evidence to Recommendations and proposed  recommendations for use of virus -like particle  chikungunya vaccine among laboratory workers Dr J. Erin Staples Arboviral Diseases Branch Centers for Disease Control and PreventionNational Center for Emerging and Zoonotic Infectious Diseases April 16 , 2025 Infections among laboratory workers  •At least 44 chikungunya virus infections identified among laboratory  workers worldwide over ~50 years1–3 -43 cases overt disease, 1 asymptomatic infection, no…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/03-staples-chikungunya-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 19}
{"title": "04 Hills chikungunya 508", "content": "Surveillance for adverse events following use of \nlive attenuated chikungunya vaccine and its use \namong travelersNational Center for Emerging and Zoonotic Infectious Diseases\nDr. Susan Hills\nCDC Lead, Chikungunya Vaccines Work Group\nArboviral Diseases Branch\nDivision of Vector -Borne Diseases\nFort Collins, Colorado\nAdvisory Committee on Immunization Practices meeting\nApril 16 , 2025\nBackground on live attenuated \nchikungunya vaccine\nLive attenuated chikungunya vaccine (CHIK -LA) \n•Manufactured by Valneva and called IXCHIQ\n•Licensed in United States in November 2023 for individuals aged ≥18 years\n•Single dose primary schedule\n•Licensed based on immunogenicity and safety data in ~3,500 adults\n\nLocal and systemic adverse events in pivotal Phase 3 trial\n•Safety data from 3,082 subjects\n•Solicited local reactions  within 10 days after vaccination\n-15% in vaccinees vs 11% in placebo recipients\n•Solicited systemic adverse events  (AE) within 10 days after vaccination\n-50% in vaccinees vs 27% in placebo recipients\n-Most common were headache, fatigue and myalgia in ~25% –30% of vaccinees\nSchneider M et al. Safety and immunogenicity of a single -shot live -attenuated chikungunya vaccine: a double -blind, multicentre , randomised , placebo- controlled, phase 3 trial. Lancet 2023; 401: 2138 –2147. \nComparison of adverse events in 18 –64 years and ≥65 years*\n18–64 years ≥65 years\nVaccine  \n(n=2,736)(95% CI) Placebo \n(n=916)(95% CI) Vaccine \n(n=346)(95% CI) Placebo \n(n=117)(95% CI)\nAny related AE 52% (50%– 54%) 32% (29% –35%) 46% (41%– 52%) 26% (18% –35%) \nAny related \nsevere AE2% (2%– 3%) 0.1% (0%–0.6%) 1% (0.3%– 3%) 0 (0%–3%) \n*Data from pivotal Phase 3 trial\nComparison of adverse events in 18 –64 years and ≥65 years*\n18–64 years ≥65 years\nVaccine  \n(n=2,736)(95% CI) Placebo \n(n=916)(95% CI) Vaccine \n(n=346)(95% CI) Placebo \n(n=117)(95% CI)\nAny related AE 52% (50%– 54%) 32% (29% –35%) 46% (41%– 52%) 26% (18% –35%) \nAny related \nsevere AE2% (2%– 3%) 0.1% (0%–0.6%) 1% (0.3%– 3%) 0 (0%–3%) \n*Data from pivotal Phase 3 trial\n•Fever ≥100.4° F (38° C) and ≥1 of:\n•Symptom onset within 30 days of vaccination Chikungunya- like adverse reactions (1)\n- Arthralgia or arthritis\n- Myalgia\n- Headache\n- Back pain\n- Rash\n- Lymphadenopathy\n- Certain neurologic, cardiac, or ocular symptoms\nPackage insert – IXCHIQ (https://www.fda.gov/vaccines -blood -biologics/ixchiq)\n•Chikungunya -like adverse reactions \n-11.7%  of vaccine recipients and 0.6% of placebo recipients \n•Severe reactions  preventing daily activity or requiring medical \nintervention\n-1.6%  vaccine recipients vs 0% of placebo recipients\n•Prolonged reactions  with  duration ≥30 days\n-0.5%  vaccine recipients vs 0% of placebo recipients\nChikungunya- like adverse reactions (2)\nTwo serious adverse events considered related to vaccination\n•58-year -old female, history of \nfibromyalgia and hypertension\n•Severe myalgia\n•Hospitalized for 6 days for pain \nmanagement and diagnostic procedures•66-year -old male, history of \nhypertension\n•Myalgia, high fever, atrial fibrillation, \nand hypovolemic hyponatremia \n•Hospitalized  for 4 days\nFDA Clinical Review Memo (https://www.fda.gov/vaccines -blood -biologics/ixchiq)\nACIP Work Group summary of CHIK -LA safety in Evidence \nto Recommendations, February 2024\n•Reactogenic vaccine but similar adverse event rates to some other \nvaccines \n•Important to monitor for rare adverse events post- licensure as sample \nsize of ~3,500 vaccinated subjects too small to detect rare events\nPost -marketing studies\n•FDA-required post -marketing studies\n-Vaccine effectiveness study in persons aged ≥12 years with safety component (Brazil)\n-Pragmatic randomized controlled trial in ≥10,000 individuals to assess effectiveness \nand safety\nPost -marketing studies\n•FDA-required post -marketing studies\n-Vaccine effectiveness study in persons aged ≥12 years with safety component (Brazil)\n-Pragmatic randomized controlled trial in ≥10,000 individuals to assess effectiveness \nand safety\n•Additional safety data collection\n-Valneva conducting safety study of 5,000 U.S. travelers for medically attended \nadverse events of special interest\n-Observational registry study of pregnant women in Brazil\nPost -licensure surveillance for adverse \nevents following use of CHIK- LA\n•National reporting system for adverse events (AE) following vaccination co- managed by CDC \nand FDA\n•Designed to detect rare or previously unreported AE or changes in reporting patterns that \nmight signal a potential safety concern that warrants further investigation\n•Anyone (e.g., healthcare providers, patients, vaccine manufacturers) can submit reports\n•Effective in intended role as early warning system but limitations includeVaccine Adverse Event Reporting System (VAERS)\n-Under -and over -reporting, variable report quality and \naccuracy, lack of data on vaccine doses administered, \nand lack of unvaccinated comparator group\n•Generally cannot determine if AEs caused by \nvaccine\nTimeline\nLicensure \nNovember 2023ACIP \nrecommendations \nFebruary 2024Exact timing of \ndistribution \nunknown*\n*First report (non -serious event ) to VAERS received May 6, 2024 \n28 AEs reported to VAERS after CHIK -LA vaccine \nadministered in May -Dec 2024*\n*Excludes 1 foreign report (non- serious)28 AEs reported \n22 non- serious 6 serious\n22 n on-serious AEs\n22 non- serious AE\n10 chikungunya -like \nadverse reactions4 arthralgia or \narthritis without \nfever8 other*\n*Syncope (n=1), flushing (n=1), rash/headache (n=1), musculoskeletal pain (n=1), low grade \nfever/headache (n=2), respiratory tract symptoms (n=2)\nSerious adverse events (SAEs)\nAny adverse event associated with use of biological \nproduct, whether or not considered product -related, \nthat results in:\n•Death\n•Life-threatening adverse experience\n•Inpatient hospitalization  or prolongation of existing \nhospitalization\n•Persistent or significant disability/incapacity\n•Congenital anomaly/birth defect\n•Other medically important event  that may jeopardize \npatient and may require intervention to prevent one of the \noutcomes listedFDA definition of SAE per federal law\nCode of Federal Regulations Title 21 (https://www.ecfr.gov/current/title -21/chapter -I/subchapter -F/part -600/subpart -D/section -600.80)6 SAEs\n5 hospitalizations1 other medically \nimportant event\nAny adverse event associated with use of biological \nproduct, whether or not considered product -related, \nthat results in:\n•Death\n•Life-threatening adverse experience\n•Inpatient hospitalization  or prolongation of existing \nhospitalization\n•Persistent or significant disability/incapacity\n•Congenital anomaly/birth defect\n•Other medically important event  that may jeopardize \npatient and may require intervention to prevent one of the \noutcomes listedFDA definition of SAE per federal law\nCode of Federal Regulations Title 21 (https://www.ecfr.gov/current/title -21/chapter -I/subchapter -F/part -600/subpart -D/section -600.80)6 SAEs\n5 hospitalizations1 other medically \nimportant event\nWhen SAEs reported to VAERS, \nattempts made to collect additional \ninformation (e.g., medical records)\nCase 1: 83 -year -old male\nCase 1: 83 -year -old male\nCoronary artery disease Hypertension\nHyperlipidemia\nChronic  \nthrombocytopeniaChronic heart failure\nChronic kidney disease\nMultiple medications to treat comorbidities\nActive at baseline\n•Received CHIK -LA vaccine \nfor travel to South America \nand AfricaCase 1: 83 -year -old male\nCoronary artery disease Hypertension\nHyperlipidemia\nChronic  \nthrombocytopeniaChronic heart failure\nChronic kidney disease\nMultiple medications to treat comorbidities\nActive at baseline\nCase  1. 83 -year -old male\nDay 0: \nReceived\nCHIK -LA\n (only)\n\nCase  1. 83 -year -old male\nDay 0: \nReceived\nCHIK -LA\n (only)Day 3: \nInitial \nsymptoms\n\nCase  1. 83 -year -old male\nDay 0: \nReceived\nCHIK -LA\n (only)Day 3: \nInitial \nsymptoms\nMyalgia, arthralgia, \nmild fever, chills, headache, generalized weakness, brain fog, \nanorexia, severe \nfatigue, unsteady gait\nCase  1. 83 -year -old male\nDay 0: \nReceived\nCHIK -LA\n (only)Day 3: \nInitial \nsymptomsDay 7: Presents to ED \nwith ongoing \ngeneralized weakness\n\nCase  1. 83 -year -old male\nDay 0: \nReceived\nCHIK -LA\n (only)Day 3: \nInitial \nsymptomsDay 7: Presents to ED \nwith ongoing \ngeneralized weakness\nDetermined to have \nacute kidney injury likely from dehydration; brain MRI and head CT - no acute changes; \ndischarged home\nCase  1. 83 -year -old male\nDay 0: \nReceived\nCHIK -LA\n (only)Day 3: \nInitial \nsymptomsDay 7: Presents to ED \nwith ongoing \ngeneralized weaknessDay 11: Returned to \nhospital with persistent \nweakness; admitted\nLeft lower extremity (hip flexor) weakness, myalgia, \nfatigue\n\nCase  1. 83 -year -old male\nDay 0: \nReceived\nCHIK -LA\n (only)Day 3: \nInitial \nsymptomsDay 7: Presents to ED \nwith ongoing \ngeneralized weaknessDay 11: Returned to \nhospital with persistent \nweakness; admitted\nLeft lower extremity (hip flexor) weakness, myalgia, \nfatigue\nLeukopenia, acute on chronic thrombocytopenia, \nelevated liver function tests; declined lumbar puncture\n\nCase  1. 83 -year -old male\nDay 0: \nReceived\nCHIK -LA\n (only)Day 3: \nInitial \nsymptomsDay 7: Presents to ED \nwith ongoing \ngeneralized weaknessDay 11: Returned to \nhospital with persistent \nweakness; admitted\nLeft lower extremity (hip flexor) weakness, myalgia, \nfatigue\nLeukopenia, acute on chronic thrombocytopenia, \nelevated liver function tests; declined lumbar puncture\nCOVID, influenza A/B, RSV PCR: negative\nBlood cultures: no growth\n\nCase  1. 83 -year -old male\nDay 0: \nReceived\nCHIK -LA\n (only)Day 3: \nInitial \nsymptomsDay 7: Presents to ED \nwith ongoing \ngeneralized weaknessDay 11: Returned to \nhospital with persistent \nweakness; admitted\n\nCase  1. Encephalopathy in 83-year -old male\n•Discharge diagnosis: Encephalopathy and generalized weakness - \nsuspected association with chikungunya vaccination\n•Completely resolved after 3.5 weeks\nCase  1. Encephalopathy in 83 -year -old male\nDay 0: \nReceived\nCHIK -LA\n (only)Day 3: \nInitial \nsymptoms\nMyalgia, arthralgia, \nmild fever, chills, headache, generalized weakness, brain fog, \nanorexia, severe \nfatigue, unsteady gaitDay 7: Presents to ED \nwith ongoing \ngeneralized weakness\nDetermined to have acute kidney injury likely from dehydration\nBrain MRI and head CT \n- no acute changes\nDischarged homeDay 11: Returned to \nhospital with persistent \nweakness; admitted\nLeft lower extremity (hip flexor) weakness, myalgia, fatigue\nLeukopenia, acute on chronic thrombocytopenia, \nelevated liver function tests; declined lumbar puncture\nCOVID –19, influenza A/B, RSV PCR: negative \nBlood cultures: no growth\n\nCase  2. 77 -year -old male\nCoronary artery disease\nHypothyroidism\nSelective IgA deficiencyHypertension\nBenign prostatic \nhyperplasia\nSeveral medications to treat comorbidities\nActive at baselineHyperlipidemia\nCase  2. 77 -year -old male\nCoronary artery disease\nHypothyroidism\nSelective IgA deficiencyHypertension\nBenign prostatic \nhyperplasia\nSeveral medications to treat comorbidities\nActive at baseline•Received CHIK -LA vaccine \nfor travel to Southeast AsiaHyperlipidemia\nCase  2. 77 -year -old male\nDay 0: \nReceived\nCHIK -LA &  \nJE-VC*\n*JE-VC: Inactivated Vero cell culture -derived JE vaccine\nCase  2. 77 -year -old male\nDay 0: \nReceived\nCHIK -LA &  \nJE-VCDay 4: \nInitial \nsymptoms\n\nCase  2. 77 -year -old male\nDay 0: \nReceived\nCHIK -LA &  \nJE-VCDay 4: \nInitial \nsymptoms\nSevere fatigue, \nfever, diarrhea, myalgia, urinary urgency\n\nCase  2. 77 -year -old male\nDay 0: \nReceived\nCHIK -LA &  \nJE-VCDay 4: \nInitial \nsymptomsDay 6: \nPresented to \nUrgent Care\nDiagnosed \nwith viral illness\n\nCase  2. 77 -year -old male\nDay 0: \nReceived\nCHIK -LA &  \nJE-VCDay 4: \nInitial \nsymptomsDay 6: \nPresented to \nUrgent CareDay 8: Presented to \nhospital with \nworsening \nsymptoms; admitted\nProfound weakness with inability \nto stand and intermittent confusion; no dysuria or macroscopic hematuria\nAdmission diagnosis of fever of \nunknown origin, diarrhea, dehydration, hyponatremia, \nhypochloremia, and suspected \nurinary tract infection\n\nCase  2. 77 -year -old male\nDay 0: \nReceived\nCHIK -LA &  \nJE-VCDay 4: \nInitial \nsymptomsDay 6: \nPresented to \nUrgent CareDay 8: Presented to \nhospital with \nworsening \nsymptoms; admitted\nUrinalysis: Negative\nCase  2. 77 -year -old male\nDay 0: \nReceived\nCHIK -LA &  \nJE-VCDay 4: \nInitial \nsymptomsDay 6: \nPresented to \nUrgent CareDay 8: Presented to \nhospital with \nworsening \nsymptoms; admitted\nUrinalysis: Negative\nCOVID PCR, influenza A/B \nantigen: negative\nBlood cultures: no growth\nCase  2. 77 -year -old male\nDay 0: \nReceived\nCHIK -LA &  \nJE-VCDay 4: \nInitial \nsymptomsDay 6: \nPresented to \nUrgent CareDay 8: Presented to \nhospital with \nworsening \nsymptoms; admitted\nUrinalysis: Negative\nCOVID PCR, influenza A/B \nantigen: negative\nBlood cultures: no growth\nBrain MRI: no acute intracranial \nabnormalities\nCase  2. 77 -year -old male\nDay 0: \nReceived\nCHIK -LA &  \nJE-VC*Day 4: \nInitial \nsymptomsDay 6: \nPresented to \nUrgent CareDay 8: Presented to \nhospital with \nworsening \nsymptoms; admitted\nUrinalysis: Negative\nCOVID PCR, influenza A/B \nantigen: negative\nBlood cultures: no growth\nBrain MRI: no acute intracranial \nabnormalities\n•Discharge diagnosis: Acute metabolic encephalopathy – possible \nassociation with vaccination –  and fever of unknown origin (resolved)Case  2. Encephalopathy in 77 -year -old male\nCase  2. Encephalopathy in 77 -year -old male\nDay 0: \nReceived\nCHIK -LA &  \nJE-VCDay 4: \nInitial \nsymptomsDay 6: \nPresented to \nUrgent CareDay 8: Presented to \nhospital with \nworsening \nsymptoms; admitted\nDay 19: \nReadmitted with \nurinary retention \nfor ~24 hours \n•At ~4 months after onset: Still recovering with ongoing weaknessCase  2. Encephalopathy in 77 -year -old male: outcome\nDay 0: \nReceived\nCHIK -LA &  \nJE-VC*Day 4: \nInitial \nsymptoms\nSevere fatigue, \nfever, diarrhea, myalgia, urinary urgencyDay 6: \nPresented to \nUrgent Care\nDiagnosed with viral illnessDay 8: Presented to \nhospital with \nworsening \nsymptoms; admitted\nProfound weakness with inability to stand and intermittent confusion; no dysuria or macroscopic hematuria\nAdmission diagnosis of fever of \nunknown origin, diarrhea, dehydration, hyponatremia, \nhypochloremia, and suspected \nurinary tract infection\n*JE-VC: Inactivated Vero cell culture -derived JE vaccine\nUrinalysis: Negative\nCOVID PCR, influenza A/B \nantigen: negative\nBlood cultures: no growth\nBrain MRI: no acute intracranial \nabnormalitiesDay 19: \nReadmitted for \n~24 hours with \nurinary retentionCase  2. Encephalopathy in 77 -year -old male\nCase  3. 86-year -old male\nDiabetes mellitus\nMedications to manage comorbiditiesHypertension\nHeart failure\nHyperlipidemia AnemiaHypothyroidism\nCase  3. 86-year -old male\nDiabetes mellitus\nMedications to manage comorbiditiesHypertension\nHeart failure\nHyperlipidemia AnemiaHypothyroidism•Received CHIK -LA vaccine \nfor travel to South Asia\nCase  3. 86 -year -old male\nDay 0: \nReceived\nCHIK -LA\n\nCase  3. 86 -year -old male\nDay 0: \nReceived\nCHIK -LADay 3: \nInitial \nsymptoms\nLethargy, \ndrowsiness, \nfever\nCase  3. 86 -year -old male\nDay 0: \nReceived\nCHIK -LADay 3: \nInitial \nsymptoms\nLethargy, \ndrowsiness, \nfeverDeterioration \nin mental \nstatus, \nshortness of \nbreath\nCase  3. 86 -year -old male\nDay 0: \nReceived\nCHIK -LADay 3: \nInitial \nsymptomsDay 8: \nHospitalized, \nadmitted to ICU\nAltered mental \nstatus, acute \nencephalopathy \nsecondary to \nhyponatremia \n(118 mmol/L), \nshortness of \nbreath\nCase  3. 86 -year -old male\nDay 0: \nReceived\nCHIK -LADay 3: \nInitial \nsymptomsDay 8: \nHospitalized, \nadmitted to ICU\nHypokalemia, hypochloremia, \nhypocalcemia, hypomagnesemiaElevated liver function tests\nCase  3. 86 -year -old male\nDay 0: \nReceived\nCHIK -LADay 3: \nInitial \nsymptomsDay 8: \nHospitalized, \nadmitted to ICU\nHypokalemia, hypochloremia, \nhypocalcemia, hypomagnesemiaElevated liver function tests\nCT head: No acute abnormalities\nChest X -ray: bilateral infiltrates\nEchocardiogram: Small pericardial effusion\nCase  3. 86 -year -old male\nDay 0: \nReceived\nCHIK -LADay 3: \nInitial \nsymptomsDay 8: \nHospitalized, \nadmitted to ICU\nHypokalemia, hypochloremia, \nhypocalcemia, hypomagnesemiaElevated liver function tests\nCT head: No acute abnormalities\nChest X -ray: bilateral infiltrates\nEchocardiogram: Small pericardial effusion\nDay 13 post -vaccination serum \nsample: chikungunya virus RNA \nCase  3. 86 -year -old male\nDay 0: \nReceived\nCHIK -LADay 3: \nInitial \nsymptomsDay 8: \nHospitalized, \nadmitted to ICU\nDay 31: \nDischarged \nafter 23 -day \nhospitalization\nCase  3. Metabolic encephalopathy  in 83-year -old male\n•Discharge diagnosis: \n-Toxic metabolic encephalopathy\n-Fever possibly related to a post- vaccination inflammatory response \nwith possible superadded bacterial pneumonia\n•Mostly recovered at 1 month after discharge from hospital\nCase  4. 68-year -old male\nProstate cancer*\nMedications to manage comorbiditiesHypertension\nHypothyroidism Dyslipidemia\n*Radiation therapy pending\nCase  4. 68-year -old male\nProstate cancer*\nMedications to manage comorbiditiesHypertension\nHypothyroidism Dyslipidemia\n*Radiation therapy pending•Received CHIK -LA vaccine \nfor trip to Southeast Asia\nCase  4. 68 -year -old male\nDay 0: \nReceived\nCHIK -LA*\n*At intervals 8– 15 days earlier, received six inactivated vaccines: Tdap, influenza, polio, typhoid, Japanese encephalitis, hepatitis A\nCase  4. 68 -year -old male\nDay 0: \nReceived\nCHIK -LA\nDay 5: \nInitial symptoms\nFever, \nheadache, \nfatigue, body \nachesPhotophobia and neck \nstiffness\nCase  4. 68 -year -old male\nDay 0: \nReceived\nCHIK -LA\nDay 5: \nInitial symptomsDay 12: Hospitalized \nwith meningitis\nCase  4. 68 -year -old male\nDay 0: \nReceived\nCHIK -LA\nDay 5: \nInitial symptomsDay 12: Hospitalized \nwith meningitis\nCSF pleocytosis (109 WBC/µL with \nmononuclear predominance; 157 RBC/µL)\nCase  4. 68 -year -old male\nDay 0: \nReceived\nCHIK -LA\nDay 5: \nInitial symptomsDay 12: Hospitalized \nwith meningitis\nCSF pleocytosis (109 WBC/µL with \nmononuclear predominance; 157 RBC/µL)\nMeningoencephalitis and respiratory PCR \npanels negative, CSF culture no growth \nCase  4. 68 -year -old male\nDay 0: \nReceived\nCHIK -LA\nDay 5: \nInitial symptomsDay 12: Hospitalized \nwith meningitis\nCSF pleocytosis (109 WBC/µL with \nmononuclear predominance; 157 RBC/µL)\nMeningoencephalitis and respiratory PCR \npanels negative, CSF culture no growth \nBrain MRI, CT: no acute abnormalities\nCase  4. 68 -year -old male\nDay 0: \nReceived\nCHIK -LA\nDay 5: \nInitial symptomsDay 12: Hospitalized \nwith meningitis\nCSF pleocytosis (109 WBC/µL with \nmononuclear predominance; 157 RBC/µL)\nMeningoencephalitis and respiratory PCR \npanels negative, CSF culture no growth \nBrain MRI, CT: no acute abnormalities\nCSF chikungunya testing: IgM and \nneutralizing antibodies detected\nCase  4. 68 -year -old male\nDay 0: \nReceived\nCHIK -LA\nDay 5: \nInitial symptomsDay 12: Hospitalized \nwith meningitis\n•Discharge diagnoses: Meningismus /aseptic meningitis likely \nsecondary to recent vaccination \n•Status : Headache and fatigue initially persisted but fully recovered by \n~1 monthCase  4. Meningitis in 68- year -old male\nCase  4. Meningitis in 68- year -old male\nDay 0: \nReceived\nCHIK -LA*\n*At intervals 8– 15 days earlier, received six inactivated vaccines: Tdap, influenza, polio, typhoid, Japanese encephalitis, hepatitis ADay 5: \nInitial symptoms\nFever, \nheadache, \nfatigue, body \nachesPhotophobia and neck \nstiffnessDay 12: Hospitalized \nwith meningitis\nCSF pleocytosis (109 WBC/µL with \nmononuclear predominance; 157 RBC/µL)\nMeningoencephalitis and respiratory PCR \npanels negative, CSF culture no growth \nBrain MRI, CT: no acute abnormalities\nCSF chikungunya testing: IgM and \nneutralizing antibodies detected\nCase  5. 67-year -old male\nHyperlipidemia\nMedication to manage condition\nCase  5. 67-year -old male\nHyperlipidemia\nMedication to manage condition•Received CHIK -LA vaccine \nfor trip to central America\nCase  5. 67 -year -old male\nDay 0: \nReceived\nCHIK -LA & oral \ntyphoid vaccine*\n*19 days prior: COVID -19 and inactivated influenza vaccines\nCase  5. 67 -year -old male\nDay 0: \nReceived\nCHIK -LA & oral \ntyphoid vaccineDay 4: \nInitial \nsymptoms\nMyalgia, fever\nCase  5. 67 -year -old male\nDay 0: \nReceived\nCHIK -LA & oral \ntyphoid vaccineDay 4: \nInitial \nsymptomsDay 6: \nPalpitations\nCase  5. 67 -year -old male\nDay 0: \nReceived\nCHIK -LA & oral \ntyphoid vaccineDay 4: \nInitial \nsymptomsDay 8: Presented to \nhospital with atrial \nflutter with rapid \nventricular responseDay 6: \nPalpitations\nCase  5. 67 -year -old male\nDay 0: \nReceived\nCHIK -LA & oral \ntyphoid vaccineDay 4: \nInitial \nsymptomsDay 8: Presented to \nhospital with atrial \nflutter with rapid \nventricular responseDay 6: \nPalpitations\nElevated troponin, proBNP\nNuclear stress test: suspicious for small infarct\nCase  5. 67 -year -old male\nDay 0: \nReceived\nCHIK -LA & oral \ntyphoid vaccineDay 4: \nInitial \nsymptomsDay 8: Presented to \nhospital with atrial \nflutter with rapid \nventricular responseDay 6: \nPalpitations\nElevated troponin, proBNP\nNuclear stress test: suspicious for small infarct\nNo evidence of pulmonary embolism, normal \nthyroid -stimulating hormone \nCase  5. 67 -year -old male\nDay 0: \nReceived\nCHIK -LA & oral \ntyphoid vaccineDay 4: \nInitial \nsymptomsDay 8: Presented to \nhospital with atrial \nflutter with rapid \nventricular responseDay 6: \nPalpitations\nElevated troponin, proBNP\nNuclear stress test: suspicious for small infarct\nNo evidence of pulmonary embolism, normal \nthyroid -stimulating hormone \nCOVID, influenza, RSV PCR: negative\nCase  5. 67 -year -old male\nDay 0: \nReceived\nCHIK -LA & oral \ntyphoid vaccineDay 4: \nInitial \nsymptomsDay 8: Presented to \nhospital with atrial \nflutter with rapid \nventricular responseDay 6: \nPalpitations\n•Discharge diagnoses: atrial flutter with rapid ventricular response, \nsuspected small non- ST segment elevation myocardial infarction\n•Status : Fully recovered on discharge, medication ongoing 3 months laterCase  5. Atrial flutter and non -ST segment elevation \nmyocardial infarction in 67- year -old male \nCase  5. Atrial flutter and non -ST segment elevation \nmyocardial infarction in 67- year -old male with \nDay 0: \nReceived\nCHIK -LA & oral \ntyphoid vaccine*Day 4: \nInitial \nsymptomsDay 8: Presented to \nhospital with atrial \nflutter with rapid \nventricular response\n*19 days prior: COVID -19 and inactivated influenza vaccinesMyalgia, fever \n1 day laterDay 6: \nPalpitations\nElevated troponin, proBNP\nNuclear stress test: suspicious for small infarct\nNo evidence of pulmonary embolism, normal \nthyroid -stimulating hormone \nCOVID, influenza, RSV PCR: negative\nCase  6. 74 -year -old male\nIschemic \ncardiomyopathy\nMedications to manage comorbiditiesCoronary artery diseaseHypotensionChronic leukopenia\nChronic thrombocytopenia\nCase  6. 74 -year -old male\nIschemic \ncardiomyopathy\nMedications to manage comorbiditiesCoronary artery diseaseHypotensionChronic leukopenia•Received CHIK -LA vaccine \nfor planned travel to \nSoutheast Asia\nChronic \nthrombocytopenia\nCase  6. 74 -year -old male\nDay 0: \nReceived\nCHIK -LA \n&  JE -VC*\n*JE-VC: Inactivated Vero cell culture -derived JE vaccine\nCase  6. 74 -year -old male\nDay 3: \nInitial \nsymptomsDay 0: \nReceived\nCHIK -LA \n&  JE -VC\nFatigue, weakness, \nlightheadedness, \nmild shortness of \nbreath, noted \nhypotension \nCase  6. 74 -year -old male\nDay 3: \nInitial \nsymptomsDay 8: \nPresented \nto internistDay 0: \nReceived\nCHIK -LA \n&  JE -VC\nSevere \nhypotension \nNo evidence \nof heart \nfailure \nCase  6. 74 -year -old male\nDay 3: \nInitial \nsymptomsDay 8: \nPresented \nto internistDay 0: \nReceived\nCHIK -LA \n&  JE -VCDay 10: \nBlood \ncollection\nLeukopenia, \nthrombocytopenia\nCase  6. 74 -year -old male\nDay 3: \nInitial \nsymptomsDay 8: \nPresented \nto internistDay 0: \nReceived\nCHIK -LA \n&  JE -VCDay 15: \nFollow -up visit \nto internist\nSome \nimprovement in \nblood pressureDay 10: \nBlood \ncollection\nCase  6. 74 -year -old male#\nDay 3: \nInitial \nsymptomsDay 8: \nPresented \nto internistDay 0: \nReceived\nCHIK -LA \n&  JE -VCDay 15: \nFollow -up visit \nto internist\n#SAE as “Other medically important event”Day 10: \nBlood \ncollection\nCase  6. Worsened and prolonged hypotension in 74 -\nyear -old male\n•Final diagnosis: Episode of worsened and prolonged hypotension on the \nbackground of pre -existing cardiomyopathy and hypotension - likely \nrelated to CHIK -LA vaccination \n•Resolved within ~2 weeks\nCase  6. 74 -year -old male#\nDay 3: \nInitial \nsymptomsDay 8: \nPresented \nto internistDay 0: \nReceived\nCHIK -LA \n&  JE -VC*\n*JE-VC: Inactivated Vero cell culture -derived JE vaccineFatigue, weakness, \nlightheadedness, \nmild shortness of \nbreath, noted \nhypotension Day 15: \nFollow -up visit \nto internist\nSevere \nhypotension \nNo evidence \nof heart \nfailure Some \nimprovement in \nblood pressure\n#SAE as “Other medically important event”Day 10: \nBlood \ncollection\nLeukopenia, \nthrombocytopenia\nSummary of case characteristics (N=6)\nAge \n(yrs) Sex Key comorbiditiesCo-administered \nvaccinesSymptom \nonset (days) Discharge diagnosis(es) Chikungunya testing\n83 MaleCoronary artery disease, chronic heart failure, chronic kidney disease, hypertension, hyperlipidemia, chronic thrombocytopenia_ 3\nEncephalopathy\nGeneralized weaknessN/A\n77 MaleCoronary artery disease, hypothyroidism, benign prostatic hyperplasia, \nhyperlipidemia, hypertension, IgA \ndeficiencyJapanese encephalitis (inactivated)4\nAcute metabolic encephalopathy\nFever of unknown originN/A\n86 MaleDiabetes mellitus, heart failure, anemia, hypertension, hypothyroidism, hyperlipidemia_3Metabolic encephalopathy\nFever possibly related to post -\nvaccination inflammatory responseRT-PCR on serum on \nday 13: positive\n68 MaleProstate cancer, hypothyroidism, \nhypertension, dyslipidemia_†\n5 Aseptic meningitisIgM & neutralizing \nantibodies in CSF\n67 Male HyperlipidemiaTyphoid\n(oral, live)*4Atrial flutter\nNon -ST segment elevation myocardial \ninfarction (NSTEMI)N/A\n74 MaleIschemic cardiomyopathy, hypotension, coronary artery disease, chronic leukopenia, chronic thrombocytopeniaJapanese \nencephalitis \n(inactivated)3\nWorsened and prolonged hypotension \non background of pre -existing \ncardiomyopathy and hypotensionN/A\n*19 days prior: COVID- 19 & influenza (inactivated); †8–15 days prior: Tdap, influenza, polio, typhoid, Japanese encephalitis, hepatitis A; N/A: Not available\nAge \n(yrs) Sex Key comorbiditiesCo-administered \nvaccinesSymptom \nonset (days) Discharge diagnosis(es) Chikungunya testing\n83 MaleCoronary artery disease, chronic heart failure, chronic kidney disease, hypertension, hyperlipidemia, chronic thrombocytopenia_ 3\nEncephalopathy\nGeneralized weaknessN/A\n77 MaleCoronary artery disease, hypothyroidism, benign prostatic hyperplasia, \nhyperlipidemia, hypertension, IgA \ndeficiencyJapanese encephalitis (inactivated)4\nAcute metabolic encephalopathy\nFever of unknown originN/A\n86 MaleDiabetes mellitus, heart failure, anemia, hypertension, hypothyroidism, hyperlipidemia_3Metabolic encephalopathy\nFever possibly related to post -\nvaccination inflammatory responseRT-PCR on serum on \nday 13: positive\n68 MaleProstate cancer, hypothyroidism, \nhypertension, dyslipidemia_†\n5 Aseptic meningitisIgM & neutralizing \nantibodies in CSF\n67 Male HyperlipidemiaTyphoid\n(oral, live)*4Atrial flutter\nNon -ST segment elevation myocardial \ninfarction (NSTEMI)N/A\n74 MaleIschemic cardiomyopathy, hypotension, coronary artery disease, chronic leukopenia, chronic thrombocytopeniaJapanese \nencephalitis \n(inactivated)3\nWorsened and prolonged hypotension \non background of pre -existing \ncardiomyopathy and hypotensionN/A\n*19 days prior: COVID- 19 & influenza (inactivated); †8–15 days prior: Tdap, influenza, polio, typhoid, Japanese encephalitis, hepatitis A; N/A: Not availableSummary of case characteristics (N=6)\nAge \n(yrs) Sex Key comorbiditiesCo-administered \nvaccinesSymptom \nonset (days) Discharge diagnosis(es) Chikungunya testing\n83 MaleCoronary artery disease, chronic heart failure, chronic kidney disease, hypertension, hyperlipidemia, chronic thrombocytopenia_ 3\nEncephalopathy\nGeneralized weaknessN/A\n77 MaleCoronary artery disease, hypothyroidism, benign prostatic hyperplasia, \nhyperlipidemia, hypertension, IgA \ndeficiencyJapanese encephalitis (inactivated)4\nAcute metabolic encephalopathy\nFever of unknown originN/A\n86 MaleDiabetes mellitus, heart failure, anemia, hypertension, hypothyroidism, hyperlipidemia_3Metabolic encephalopathy\nFever possibly related to post -\nvaccination inflammatory responseRT-PCR on serum on \nday 13: positive\n68 MaleProstate cancer, hypothyroidism, \nhypertension, dyslipidemia_†\n5 Aseptic meningitisIgM & neutralizing \nantibodies in CSF\n67 Male HyperlipidemiaTyphoid\n(oral, live)*4Atrial flutter\nNon -ST segment elevation myocardial \ninfarction (NSTEMI)N/A\n74 MaleIschemic cardiomyopathy, hypotension, coronary artery disease, chronic leukopenia, chronic thrombocytopeniaJapanese encephalitis (inactivated)3\nWorsened and prolonged hypotension \non background of pre -existing \ncardiomyopathy and hypotensionN/A\n*19 days prior: COVID- 19 & influenza (inactivated); †8–15 days prior: Tdap, influenza, polio, typhoid, Japanese encephalitis, hepatitis A; N/A: Not availableSummary of case characteristics (N=6)\nAge \n(yrs) Sex Key comorbiditiesCo-administered \nvaccinesSymptom \nonset (days) Discharge diagnosis(es) Chikungunya testing\n83 MaleCoronary artery disease, chronic heart failure, chronic kidney disease, hypertension, hyperlipidemia, chronic thrombocytopenia_ 3\nEncephalopathy\nGeneralized weaknessN/A\n77 MaleCoronary artery disease, hypothyroidism, benign prostatic hyperplasia, \nhyperlipidemia, hypertension, IgA \ndeficiencyJapanese encephalitis (inactivated)4\nAcute metabolic encephalopathy\nFever of unknown originN/A\n86 MaleDiabetes mellitus, heart failure, anemia, hypertension, hypothyroidism, hyperlipidemia_3Metabolic encephalopathy\nFever possibly related to post -\nvaccination inflammatory responseRT-PCR on serum on \nday 13: positive\n68 MaleProstate cancer, hypothyroidism, \nhypertension, dyslipidemia_†\n5 Aseptic meningitisIgM & neutralizing \nantibodies in CSF\n67 Male HyperlipidemiaTyphoid\n(oral, live)*4Atrial flutter\nNon -ST segment elevation myocardial \ninfarction (NSTEMI)N/A\n74 MaleIschemic cardiomyopathy, hypotension, coronary artery disease, chronic leukopenia, chronic thrombocytopeniaJapanese \nencephalitis \n(inactivated)3\nWorsened and prolonged hypotension \non background of pre -existing \ncardiomyopathy and hypotensionN/A\n*19 days prior: COVID- 19 & influenza (inactivated); †8–15 days prior: Tdap, influenza, polio, typhoid, Japanese encephalitis, hepatitis A; N/A: Not availableSummary of case characteristics (N=6)\nclinical consult services†\nsupport enhanced surveillance\nclinical research\n†More information about clinical consults available at :\nhttps://www.cdc.gov/vaccine -safety -systems/hcp/cisa/index.html8 participating medical \nresearch centers with \nvaccine safety expertsClinical\nImmunization\nSafety\nAssessment \n(CISA) Project C IS A \n\n•Available medical records for each of neurologic (n=4) and cardiac (n=2) \nreports reviewed with experts in vaccine safety, infectious diseases, cardiology and neurology\n•For each report, at least one CISA expert considered association of CHIK -LA \nwith SAE plausible\n•However, experts noted difficulty differentiating between general reactogenicity in older patients with comorbidities leading to SAE versus chikungunya vaccine causing SAESummary of CISA review of SAEs following CHIK -LA \nreported to VAERS\n•Temporal association ≠ causal association\n•Sometimes concomitant or recent administration of other vaccines\n•Comprehensive investigations of possible etiologies not always \nconducted or available\n•Unlike in controlled clinical trials, no unvaccinated comparator groupGenerally cannot determine causality from VAERS data\nShimabukuro TT, et al. Safety monitoring in the Vaccine Adverse Event Reporting System (VAERS). Vaccine 2015;33:4398 -4405.\nAll events began within 3 –5 days of vaccination\nFor 3 patients with co -administration of other vaccines (i.e., JE, \ntyphoid), association with other vaccines less likely1-3 \nInvestigations did not indicate clear alternate etiologies for any \npatient and most (n=5) discharge summaries noted potential \nassociation with vaccination\nFor 2 cases with chikungunya laboratory testing, results \nsuggested an association with CHIK -LA Factors supporting possible causality of CHIK -LA for SAEs\n1. Rabe IB et al, Vaccine 2015;   2. Walker WL et al, Vaccine 2018;   3. Begier  EM et al. Clin Infect Dis 2004.  \nAll events began within 3 –5 days of vaccination\nFor 3 patients with co -administration of other vaccines (i.e., JE, \ntyphoid), association with other vaccines less likely1-3 \nInvestigations did not indicate clear alternate etiologies for any \npatient and most (n=5) discharge summaries noted potential \nassociation with vaccination\nFor 2 cases with chikungunya laboratory testing, results \nsuggested an association with CHIK -LA Factors supporting possible causality of CHIK -LA for SAEs\n1. Rabe IB et al, Vaccine 2015;   2. Walker WL et al, Vaccine 2018;   3. Begier  EM et al. Clin Infect Dis 2004.  \nAll events began within 3 –5 days of vaccination\nFor 3 patients with co -administration of other vaccines (i.e., JE, \ntyphoid), association with other vaccines less likely1-3 \nInvestigations did not indicate clear alternate etiologies for any \npatient and most (n=5) discharge summaries noted potential \nassociation with vaccination\nFor 2 cases with chikungunya laboratory testing, results \nsuggested an association with CHIK -LA Factors supporting possible causality of CHIK -LA for SAEs\n1. Rabe IB et al, Vaccine 2015;   2. Walker WL et al, Vaccine 2018;   3. Begier  EM et al. Clin Infect Dis 2004.  \nAll events began within 3 –5 days of vaccination\nFor 3 patients with co -administration of other vaccines (i.e., JE, \ntyphoid), association with other vaccines less likely1-3 \nInvestigations did not indicate clear alternate etiologies for any \npatient and most (n=5) discharge summaries noted potential \nassociation with vaccination\nFor 2 cases with chikungunya laboratory testing, results \nsuggested an association with CHIK -LA Factors supporting possible causality of CHIK -LA for SAEs\n1. Rabe IB et al, Vaccine 2015;   2. Walker WL et al, Vaccine 2018;   3. Begier  EM et al. Clin Infect Dis 2004.  \nCHIK -LA and SAEs in persons ≥65 years\n•Immunosenescence  affects older person’s ability to adequately control \nreplication of live attenuated vaccine virus\n-Example: With live attenuated yellow fever vaccine, SAEs more frequent in older \npersons, and age ≥ 60 years is precaution for use\n•Wild -type chikungunya virus infections more likely to result in severe \ndisease in older adults\nEstimating incidence of SAEs after CHIK -LA\n•Difficult as limited  data on vaccine doses distributed  and very limited  data \non doses administered\n•Obtained data from commercial source (IQVIA; private -sector company that \nprovides healthcare data)\n-Sales data : Weekly Sales Perspectives (WSP) data are unprojected (i.e., actual) \nsales for prescription products (vaccinations) sold to retail, non -retail, and mail \nchannels and capture about ~90% of total sales*\n-Administration data : National Prescription Audit (NPA) data represent projected \nestimates  of vaccinations administered in retail and long -term care pharmacies\n*Information from IQVIA\nConfidential and pre -decisional – for official use onlyCHIK -LA (IXCHIQ) weekly and cumulative sales  as of week ending December 27, 2024 \nIQVIA SMART Weekly Sales Perspective (WSP)\n13,891 total \ndoses \ndistributed \nPharmacy total = 1,275 (9%) Medical office total = 12,616 (91%)\nConfidential and pre -decisional – for official use onlyCHIK -LA (IXCHIQ) weekly and cumulative vaccinations administered in pharmacies , \nas of week ending December 27, 2024. IQVIA SMART NPA Weekly Extended Insights\nEstimated\n928 doses \nadministered \nin pharmacies\nConfidential and pre -decisional – for official use onlyCHIK -LA (IXCHIQ) pharmacy administrations by age, March 3– December 27, 2024\nIQVIA SMART NPA Weekly Extended Insights\n53% doses \nadministered \nto individuals \naged ≥65 years\nN=928\nNo. \neventsEstimated rate of events \nper 100,000 doses administered\n(95% CI)Estimated rate of doses administered \nresulting in 1 event\n(95% CI)\nSAEs 682 per 100,000\n(30–180) 1 SAE per 1,220 doses\n(1 per 3,333 doses to 1 per 556 doses)\n*Based on VAERS reports, IQVIA data on doses distributed (N=13,891 doses), and IQVIA data that 52.7% (n=7,320) administered to p ersons aged ≥65 yrsRisk estimates for SAEs and hospitalizations among persons aged \n≥65 years*\nNo. \neventsEstimated rate of events \nper 100,000 doses administered\n(95% CI)Estimated rate of doses administered \nresulting in 1 event\n(95% CI)\nSAEs 682 per 100,000\n(30–180) 1 SAE per 1,220 doses\n(1 per 3,333 doses to 1 per 556 doses)\nHospitalizations 568 per 100,000\n(20–160) 1 hospitalization per 1,471 doses\n(1 per 5,000 doses to 1 per 625 doses)\n*Based on VAERS reports, IQVIA data on doses distributed (N=13,891 doses), and IQVIA data that 52.7% (n=7,320) administered to p ersons aged ≥65 yrsRisk estimates for SAEs and hospitalizations among persons aged \n≥65 years*\nLimitations of risk estimates\n•Calculations limited by potential imprecision in numerator and \ndenominator data\n-Unknown completeness of reporting of events to VAERS \n-Potential inaccuracies in vaccine administration data overall and by age group\n•All VAERS SAE reports included in calculations but cannot confirm causal link between vaccination and all reported events\n•Overall low certainty in estimates\n•Updated data as of March 21, 2025\n-0 SAEs  and 9 non- serious AEs reported to VAERS in United States*\n-Additional ~4,250 CHIK -LA doses sold# \n•Risk estimates not updated for this presentation \n-Delays in CHIK -LA reports to VAERS (median 13 days) \n-~2,375 doses sold in last ~2 weeks of 2024 and likely not \nadministered in 2024\n-Unknown impact of CDC alert in February 2025 about \nhospitalizations after CHIK -LA in ages ≥65 years\n-With updated data, risk estimates lower but within 95% confidence limits of previous estimates\n Update: 2025  VAERS data\n*Excludes 6 (non -serious) reports from other countries; #IQVIA data \nhttps://www.cdc.gov/chikungunya/prevention/chikungunya -vaccine.html\nWork Group considerations regarding SAEs \nfollowing CHIK -LA\nAll SAEs in persons aged ≥65 years\nFindings considered preliminary because in clinical trials and post -licensure use, CHIK -LA only administered to \n~7,700 persons aged ≥65 years\nVAERS intended to be early warning system to flag potential safety issues; signal identified for persons aged ≥65 \nyears, but further investigation warranted to better define true risk \nFor individual travelers aged ≥65 years, risk -benefit assessment needed to weigh risks of disease vs risks of \nvaccination because vaccine use might be supported in certain higher -risk settings (e.g., outbreak) given known \nrisks for severe disease and hospitalization in this age groupFactors considered by Work Group \nAll SAEs in persons aged ≥65 years\nAssociation of CHIK -LA with SAEs is plausible, but causal association for each event not determined\nFindings considered preliminary because in clinical trials and post -licensure use, CHIK -LA only administered to \n~7,700 persons aged ≥65 years\nVAERS intended to be early warning system to flag potential safety issues; signal identified for persons aged ≥65 \nyears, but further investigation warranted to better define true risk \nFor individual travelers aged ≥65 years, risk -benefit assessment needed to weigh risks of disease vs risks of \nvaccination because vaccine use might be supported in certain higher -risk settings (e.g., outbreak) given known \nrisks for severe disease and hospitalization in this age groupFactors considered by Work Group \nAll SAEs in persons aged ≥65 years\nAssociation of CHIK -LA with SAEs is plausible, but causal association for each event not determined\nFindings considered preliminary because in clinical trials and post -licensure use, CHIK -LA only administered to \n~7,700 persons aged ≥65 years\nVAERS intended to be early warning system to flag potential safety issues; signal identified for persons aged ≥65 \nyears, but further investigation warranted to better define true risk \nFor individual travelers aged ≥65 years, risk -benefit assessment needed to weigh risks of disease vs risks of \nvaccination because vaccine use might be supported in certain higher -risk settings (e.g., outbreak) given known \nrisks for severe disease and hospitalization in this age groupFactors considered by Work Group \nAll SAEs in persons aged ≥65 years\nAssociation of CHIK -LA with SAEs is plausible, but causal association for each event not determined\nFindings considered preliminary because in clinical trials and post -licensure use, CHIK -LA only administered to \n~7,700 persons aged ≥65 years\nVAERS intended to be early warning system to flag potential safety issues; signal identified for persons aged ≥65 \nyears, but further investigation warranted to better define true risk \nFor individual travelers aged ≥65 years, risk -benefit assessment needed to weigh risks of disease vs risks of \nvaccination because vaccine use might be supported in certain higher -risk settings (e.g., outbreak) given known \nrisks for severe disease and hospitalization in this age groupFactors considered by Work Group \nAll SAEs in persons aged ≥65 years\nAssociation of CHIK -LA with SAEs is plausible, but causal association for each event not determined\nFindings considered preliminary because in clinical trials and post -licensure use, CHIK -LA only administered to \n~7,700 persons aged ≥65 years\nVAERS intended to be early warning system to flag potential safety issues; signal identified for persons aged ≥65 \nyears, but further investigation warranted to better define true risk \nFor individual travelers aged ≥65 years, risk -benefit assessment needed to weigh risks of disease vs risks of \nvaccination because vaccine use might be supported in certain higher -risk settings (e.g., outbreak) given known \nrisks for severe disease and hospitalization in this age groupFactors considered by Work Group \nAge ≥65 years should be a precaution * for use of CHIK -LA\n•In general, vaccination should be deferred\n•Vaccination might be indicated if benefit from protection from vaccination \noutweighs risk for adverse reaction\n*https://www.cdc.gov/vaccines/hcp/imz -best -practices/contraindications -precautions.html\nWork Group proposes revising recommendations for \nuse of CHIK -LA among travelers\n•In accordance with updated Evidence to Recommendations for travelers \npresented in earlier presentation for CHIK -VLP\n•In consideration of safety signal following use of vaccine in persons aged ≥65 years \nExisting CHIK -LA recommendations for travelers*\nChikungunya vaccine is recommended  for persons aged ≥18 years traveling \nto a country or territory where there is a chikungunya outbreak.\nIn addition, chikungunya vaccine may be considered for the following \npersons traveling to a country or territory without an outbreak but with \nevidence of chikungunya virus transmission among humans within the last 5 years\n-Persons aged >65 years, particularly those with underlying medical conditions, \nwho are likely to have at least moderate exposure to mosquitoes, OR\n-Persons staying for a cumulative period of 6 months or more \n*Approved in February 2024\nExisting CHIK -LA recommendations for travelers*\nChikungunya vaccine is recommended  for persons aged ≥18 years traveling \nto a country or territory where there is a chikungunya outbreak.\nIn addition, chikungunya vaccine may be considered for the following \npersons traveling to a country or territory without an outbreak but with \nevidence of chikungunya virus transmission among humans within the last 5 years\n-Persons aged >65 years, particularly those with underlying medical conditions, \nwho are likely to have at least moderate exposure to mosquitoes, OR\n-Persons staying for a cumulative period of 6 months or more \n*Approved in February 2024\nACIP recommends live attenuated chikungunya vaccine or persons aged ≥18 \nyears traveling to a country or territory where there is a chikungunya \noutbreak.\nIn addition, live attenuated chikungunya vaccine may be considered  for \npersons aged ≥18 years# traveling or taking up residence in a country or \nterritory without an outbreak but with elevated risk for US travelers if \nplanning travel for an extended period of time e.g., 6 months or more.Revised draft recommendations for CHIK -LA among \ntravelers#\n#Age ≥65 years is a precaution for use of CHIK -LA\nArboviral Diseases Branch, CDC\n•Rebekah Sutter\n•Erin Staples\nImmunization Safety Office, CDC\n•Sarah Meyer\n•Michael McNeil\n•Elaine MillerAcknowledgements\nImmunization Services Division, CDC\n•Seth Meador\n•Suchita Patel \nClinical Immunization Safety \nAssessment (CISA) vaccine safety \nexperts\nFor more information, contact CDC\n1-800- CDC- INFO (232 -4636)\nTTY:  1 -888- 232- 6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.", "summary": "Surveillance for adverse events following use of  live attenuated chikungunya vaccine and its use  among travelersNational Center for Emerging and Zoonotic Infectious Diseases Dr. Susan Hills CDC Lead, Chikungunya Vaccines Work Group Arboviral Diseases Branch Division of Vector -Borne Diseases Fort Collins, Colorado Advisory Committee on Immunization Practices meeting April 16 , 2025 Background on live attenuated  chikungunya vaccine Live attenuated chikungunya vaccine (CHIK -LA) …", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/04-Hills-chikungunya-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 127}
{"title": "05 Hills chikungunya 508", "content": "Clinical guidance for use of virus -like particle \nchikungunya vaccine in pregnant and breastfeeding \nwomenNational Center for Emerging and Zoonotic Infectious Diseases\nSusan Hills MBBS MTH\nCDC Lead, Chikungunya Vaccines Work Group\nArboviral Diseases Branch\nDivision of Vector- Borne Diseases\nFort Collins, ColoradoDana Meaney- Delman, MD MPH FACOG\nPrincipal Deputy Director and Chief Medical Officer\nNational Center on Birth Defects and Developmental \nDisabilities\nChamblee, Georgia\nAdvisory Committee on Immunization Practices meeting \nApril 16 , 2025\nClinical guidance for use of virus -like \nparticle chikungunya vaccine (CHIK- VLP) in \npregnant women\n•Clinical disease similar to non -pregnant individualsPresentation of chikungunya among pregnant women\n•Adverse outcomes such as fetal loss, stillbirth, or preterm birth \ndocumented but rare\n-Mouse studies and examination of placentas from infected women suggest \nplacenta is refractory to chikungunya virus infection1,2 \n•Infection commonly  results in adverse neonatal outcomes if pregnant \nwoman infected around time of delivery\n-Intrapartum transmission occurs in ~30% –50% cases3–6 \n-Mechanism hypothesized to be maternal blood entering fetal circulation by placental barrier breaches from uterine contractions during labor Outcomes of chikungunya virus infection during \npregnancy\n1. Fritel   X et al, Emerg  Infect Dis 2010; 2. Couderc T et al, PLoS Pathog 2008; 3. Gerardin P et al, PLoS Medicine 2008; 4. Ramful D et al, Ped Infect Dis J 2007; 5. \nTorres JR et al, Int J Infect Dis 2016; 6. Senanayake MP et al, Ceylon Med J 2009.\n•Severe and sometime fatal illness\n-In one prospective study 53% (10 of 19 neonates) had severe disease1 \n•Presentations include encephalopathy, sepsis -like illness, cardiac, \ndermatologic, and hemorrhagic manifestations\n•Neurocognitive outcomes often poor, particularly if initial clinical \npresentation with encephalopathyDisease in neonates infected via intrapartum transmission\nBin S et al, Clin Case Rep 2023\n Jebain  J et al, ID Cases 2020\n Villamil -Gomez W et al, J Trop Ped 2015\n1. Gerardin  P et al, PLoS  Medicine 2008\n•Young infants infected via \nmosquito -borne transmission also \nat risk for severe disease, particularly during first few months of life\n•Clinical presentations similar to infected neonates Chikungunya and young infants\nValamparampil  JJ et al, Ind J Ped 2009\nGupta D et al, Ind J Ped 2015\n•No data available on immunologic response to CHIK -VLP administered \nto pregnant women\n•General principles of maternal vaccination and experience with other \nvaccines\n-Transplacental transfer of antibodies confers protection with most vaccines\n-Examples of benefits: Decreased hospitalization rates in infants (e.g., \ninfluenza, COVID -19, RSV vaccines) and decreased preterm birth risk (e.g., \nCOVID -19 vaccine)CHIK -VLP vaccination during pregnancy: Immunogenicity\n•Data insufficient to determine whether any safety risks from vaccination \nduring pregnancy as pregnancy an exclusion criteria in clinical trials\n•Only one pregnant woman inadvertently vaccinated, was in 1st trimester\n-Phase ll study with formulation of vaccine* different to licensed product\n-History of 2 ectopic pregnancies\n-Last menstrual period 11 days prior to vaccination\n-Ectopic pregnancy detected 24 days after vaccination and assessed as \nunrelated to vaccinationCHIK -VLP vaccination during pregnancy: Safety\n*20µg dose of unadjuvanted vaccine\n•DART study in rabbits\n-Administered equivalent of human dose of vaccine on 5 occasions (i.e., twice \nprior to mating, twice during gestation, and once during lactation)\n-Postnatal survival rate within 28 days was lower for kits born to vaccinated \nmothers ( 42% ; 95% CI : 32% –53%) compared with kits in control group ( 69% ; \n95% CI 58% –80%)\n-No adverse effects on other postnatal development parameters\n•DART study in rats\n-Reduced pup survival rates not observedVaccination during pregnancy: Developmental and \nreproductive toxicology (DART) studies\n•Travelers and laboratory workers \n•Persons in U.S. territories and states with risk of chikungunya virus \ntransmissionGroups for whom clinical guidance will be relevant\n•Protect pregnant woman from disease\n•Avoid maternal infection around time of delivery to prevent \nintrapartum virus transmission and severe disease in newborn\n•Transplacental transfer of antibodies might also protect young infant from mosquito -borne transmission and severe diseaseObjectives of vaccinating pregnant women against \nchikungunya\nPregnant women should avoid the risk for chikungunya virus infection, if \npossible (e.g., by avoiding travel to an area with virus transmission particularly during an outbreak). Proposed clinical guidance for use of CHIK -VLP in \npregnant women\nPregnancy is a precaution for vaccination with CHIK -VLP based on the lack of \nsafety and immunogenicity data in pregnant women and potential safety \nconcerns from the toxicology study in rabbits. \nIn general, vaccination should be deferred until after delivery. However, in specific \ncircumstances it might be warranted. If the risk of infection is high and exposure \ncannot be avoided, a health care provider should discuss with a pregnant woman \nthe potential risks of chikungunya virus infection and the potential benefits and \nrisks of vaccination so that vaccination can be considered. \nCHIK -VLP should ideally be administered a minimum of 2 weeks prior to the \nexpected date of delivery, and preferably earlier, to allow protection around the \ntime of delivery. Proposed clinical guidance for use of CHIK -VLP in \npregnant women (2)\nIf pregnant women choose to be vaccinated, deferring vaccination until \nafter the 1st trimester (after 14 weeks gestation) might be preferred until \nthere are further data to clarify any potential concerns from the animal \ntoxicology data. In addition, it is estimated that 20% –25% of all \npregnancies lead to pregnancy loss, and the highest rates occur in the 1st \ntrimester, so avoiding vaccination in the 1st trimester would avoid any \nassociation with an unrelated pregnancy loss.Proposed clinical guidance for use of CHIK -VLP in \npregnant women (3)\nIf both CHIK -VLP and CHIK -LA are available, vaccination with CHIK -VLP \nwould be preferred . Although there are no data, this is based on general \nprinciples that vaccination with non- live vaccines is preferred over \nvaccination with live vaccines for pregnant women. Proposed clinical guidance for use of CHIK -VLP in \npregnant women (4)\nGuidance maximizing benefits while minimizing \npotential risks of vaccination during pregnancy\n1. Avoid risk of chikungunya virus exposure, if possible\n2. In general, defer vaccination until after delivery\n3. If exposure risk high, consider vaccination given risk for severe adverse \noutcomes of infection particularly if intrapartum transmission occurs\n4. If consider vaccination, where possible avoid 1st trimester and ideally \nadminister >2 weeks before delivery\n5. If both CHIK -VLP and CHIK -LA available, vaccination with non- live CHIK -\nVLP preferred\nClinical guidance for use of CHIK- VLP in \nbreastfeeding women\n•Chikungunya viral ribonucleic acid (RNA) detected in breast milk on \nvery rare occasions1,2\n-No studies have reported detection of replicating virus\n•Case report describes mother with chikungunya and chikungunya virus \nRNA detected in her breast milk who was breastfeeding her 3- month -\nold infant1 \n-No symptoms or laboratory evidence of infection in infantChikungunya and breastfeeding\n1. Campos GS et al, Pediatr  Infect Dis J 2017; 2. De Paula Souza et al, Transl  Res 2023.  \n•No data on any benefits or risks of breastfeeding after vaccination with \nCHIK -VLP , including whether chikungunya antibodies present in breast \nmilk post -vaccination\n•In toxicology studies in rabbits and rats, no impact of vaccination on \nlactation was observedCHIK -VLP and breastfeeding \n•To protect the woman from chikungunya\n•Possible added benefit to reduce risk of infection for young infant by \ntransfer of protective antibodies through breast milkObjectives of vaccinating breastfeeding women \nBreastfeeding women and their infants should avoid the risk for \nchikungunya virus infection, if possible (e.g., by avoiding travel to an area \nwith transmission particularly during an outbreak). \nBest practice guidelines1 for immunization note that non -live vaccines \npose no risk for mothers who are breastfeeding or their infants. Proposed clinical guidance for use of CHIK -VLP in \nbreastfeeding women*\n*Breastfeeding not a contraindication or precaution for vaccination with CHIK -VLP\n1. https://www.cdc.gov/breastfeeding/breastfeeding -special- circumstances/vaccinations -medications -drugs/vaccinations.html\n•Haben Debessai, Division of Birth Defects and Infant Disorders\n•Erin Staples, Division of Vector- Borne Diseases\n•ACOG and AAP members for their review of draft clinical guidance \n•Chikungunya Vaccines Work Group membersAcknowledgements\nFor more information, contact CDC\n1-800- CDC- INFO (232 -4636)\nTTY:  1 -888- 232- 6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.", "summary": "Clinical guidance for use of virus -like particle  chikungunya vaccine in pregnant and breastfeeding  womenNational Center for Emerging and Zoonotic Infectious Diseases Susan Hills MBBS MTH CDC Lead, Chikungunya Vaccines Work Group Arboviral Diseases Branch Division of Vector- Borne Diseases Fort Collins, ColoradoDana Meaney- Delman, MD MPH FACOG Principal Deputy Director and Chief Medical Officer National Center on Birth Defects and Developmental  Disabilities Chamblee, Georgia Advisory…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/05-Hills-chikungunya-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 23}
{"title": "01 Jones Maternal Peds RSV 508", "content": "Maternal/Pediatric Respiratory Syncytial Virus (RSV) \nWork Group​\nJefferson Jones MD MPH FAAP\nCo-Lead, Maternal/Pediatric RSV Work Group  \nPresenting on behalf of \nHelen Chu, MD, MPH\nChair, Maternal/Pediatric RSV Work Group  \nACIP Meeting\nApril 16, 2025\n1U.S. Centers for Disease Control and Prevention\n\nCDC and ACIP recommend all infants should be protected against \nsevere RSV disease with either maternal RSV vaccine or nirsevimab\nMaternal vaccine\nAbrysvo , Pfizer  \n*Either  maternal RSV vaccine or nirsevimab is given to protect infants against severe RSV disease – only one \nis needed in most instances \nPregnant women 32 through 36 \nweeks’ gestation\nAdminister September through \nJanuary in most of \nthecontinental United States†All infants <8 months* \nSecond season dose for children \nages 8 –19 months at increased risk \nof severe RSV disease \nAdminister October through March \nin most of the continental United \nStates†(as early as possible¥)\n† Timing of administration for RSV immunization may differ in jurisdictions with RSV seasonality that differs from most of th e continental United States; ¥ The optimal timing for nirsevimab administration is \nshortly before the RSV season begins (e.g., October –November), or within a baby's first week of life if born October through Mar ch (ideally during the birth hospitalization.)Nirsevimab\nBeyfortus , Sanofi & AstraZeneca \nToday we will be reviewing data on a second, long -acting monoclonal \nantibody for protection of infants from severe RSV disease\nMaternal vaccine\nAbrysvo , Pfizer  \n*Either  maternal RSV vaccine or an infant antibody is given to protect infants against severe RSV disease – \nonly one is needed in most instances \nPregnant women 32 \nthrough 36 weeks’ \ngestation\nAdminister \nSeptember through \nJanuary in most of \nthecontinental \nUnited States†All infants <8 months* \nSecond season dose for \nchildren ages 8 –19 months \nat increased risk of severe \nRSV disease \nAdminister October through \nMarch in most of the \ncontinental United States † \n(as early as possible¥)Nirsevimab\nBeyfortus , Sanofi & \nAstraZeneca Clesrovimab\nMerck\nCurrently not FDA approved\nTarget action date: 6/10/25\nAll infants <8 months* \nAdminister October \nthrough March in most of \nthe continental United \nStates † (as early as \npossible¥)\n† Timing of administration for RSV immunization may differ in jurisdictions with RSV seasonality that differs from most of th e continental United States; ¥ The optimal timing for nirsevimab administration is \nshortly before the RSV season begins (e.g., October –November), or within a baby's first week of life if born October through Mar ch (ideally during the birth hospitalization.)\n•September 2024\n-Maternal/Pediatric RSV work group reviewed and discussed data from Merck on \nsafety and efficacy of clesrovimab \n•October 2024\n-ACIP reviewed and discussed data from Merck on safety and efficacy of \nclesrovimab and work group interpretation of these data\n•November 2024 – April 2025\n-Maternal/Pediatric RSV work group reviewed and discussed\n•GRADE (Grading of Recommendations, Assessment, Development, and \nEvaluations) for clesrovimab \n•Evidence to Recommendations Framework for clesrovimabTimeline of Maternal/Pediatric RSV work group and \nACIP review of clesrovimab  \n•Evidence to Recommendation Framework: Clesrovimab — Ms. Danielle \nMoulia (CDC/NCIRD)\n•Clinical Considerations — Dr. Jefferson Jones (CDC/NCIRD)Today’s agenda: April 16, 2025\n5\n•FDA has set a Prescription Drug User Fee Act (PDUFA) date, or target date for \nregulation action, of June 10, 2025 , for clesrovimab .\n•June 2025 ACIP meeting\n-Presentation of any updates to the Evidence to Recommendation Framework and \nClinical Consideration for clesrovimab \n-Vote on recommendation of clesrovimab  (pending FDA regulatory action)Clesrovimab : Looking forward \n6Source: Merck Press Release, 12/17/2024: https://www.merck.com/news/merck -announces -fda-acceptance -of-biologics -license -application -for-clesrovimab -an-investigational -\nlong -acting -monoclonal -antibody -designed -to-protect -infants -from -rsv-disease -during -their -first-rsv/\nWork group members (external)\nACIP Members\nHelen Chu (chair)\nOliver Brooks\nDenise JamiesonConsultants\nCody Meissner (Dartmouth Geisel School of Medicine)\nKevin Ault (Western Michigan University)\nPablo Sanchez (Nationwide Children’s Hospital)\nLiaisons\nJames McAuley (IDSA)\nNicole Chaisson  (AAFP)\nSean O’Leary (AAP)\nJennifer Schuster (PIDS)\nMolly Howell (AIM)\nStacy Buchanan (NAPNAP)\nCaitlin Newhouse (CSTE)Ex Officio Members\nLucia Lee (FDA -CBER)\nYodit Belew (FDA -CDER)\nPrabha Viswanathan (FDA -CDER)\nYugenia Hong -Nguyen (FDA -CDER)\nSonnie Kim (NIH -NIAID)\nApril Killikelly (Public Health Agency of Canada)\nElissa Abrams  (Public Health Agency of Canada)\nJessica Lee (CMS/CMCS)\nTerry Dalle -Tezze (HRSA)\nMatthew Clark (IHS)\n7\nWork group members (CDC)\nAmanda Payne\nNoelle Molinari\nFiona Havers\nPragna Patel\nRuth Link -Gelles\nMonica Godfrey\nHeidi Moline\nHannah Rosenblum\nManisha Patel\nHeather Scobie\nMichele Hlavsa CDC ACIP Staff\nMelinda Wharton\nStephanie Thomas\nJessica MacNeilMonica Patton\nJarrett Gartin\nDennis Wang\nJordan Singleton\nFatimah Dawood\nAgustin Lopez\nLakshmi Panagiotakopoulos\nSuzanne Heitfeld\nMolly Gaines -McCollom\nAmber Rose Kautz\nAllison CieslaCDC\nJefferson Jones (co -lead)\nDanielle Moulia (co -lead)\nMeredith McMorrow\nMila Prill\nNatalie Thornburg\nIsmael Ortega -Sanchez\nMelissa Coughlin\nJamison Pike\nLauren Roper\nTami Skoff\nAngie Campbell\nMichael Melgar\nAmadea BrittonChristine Olson\nAnne Hause\nAndrew Leidner\nDavid Shay\nPedro Moro\nTarayn  Fairlie\nJohn Su\nMicheal McNeal\nJulianne Gee \nNaomi Tepper\nEllen Boundy\nAlaya Koneru\nMelissa Taylor\nEbony Thomas\n8\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position \nof the U.S. Centers for Disease Control and Prevention.\nThank you", "summary": "Maternal/Pediatric Respiratory Syncytial Virus (RSV)  Work Group​ Jefferson Jones MD MPH FAAP Co-Lead, Maternal/Pediatric RSV Work Group   Presenting on behalf of  Helen Chu, MD, MPH Chair, Maternal/Pediatric RSV Work Group   ACIP Meeting April 16, 2025 1U.S. Centers for Disease Control and Prevention  CDC and ACIP recommend all infants should be protected against  severe RSV disease with either maternal RSV vaccine or nirsevimab Maternal vaccine Abrysvo , Pfizer   *Either  maternal RSV…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/01-Jones-Maternal-Peds-RSV-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 9}
{"title": "02 Moulia maternal peds RSV 508", "content": "Evidence to Recommendations Framework : \nClesrovimab\nDanielle Moulia, MPH \nCo-Lead, Maternal/Pediatric RSV Work Group  \nAdvisory Committee on Immunization Practices\nApril 16, 2025\n1U.S. Centers for Disease Control and Prevention\n\nPolicy Question\n•Should clesrovimab  be recommended for all infants <8 months of age born \nduring or entering their first RSV season?\n2\nEvidence to Recommendations ( EtR) Framework\nEtR Domain Question(s)\nPublic Health Problem ▪Is the problem of public health importance?\nBenefits and Harms ▪How substantial are the desirable anticipated effects?\n▪How substantial are the undesirable anticipated effects?\n▪Do the desirable effects outweigh the undesirable effects?\nValues ▪Does the target population feel the desirable effects are large relative \nto the undesirable effects?\n▪Is there important variability in how patients value the outcome?\nAcceptability ▪Is the intervention acceptable to key stakeholders?\nFeasibility ▪Is the intervention feasible to implement?\nResource Use ▪Is the intervention a reasonable and efficient allocation of resources?\nEquity ▪What would be the impact of the intervention on health equity?\n3\nEtR Domain: Public Health Problem\nIs RSV -associated disease among infants <8 months of age of public health \nimportance? \n4\nRSV burden is high in children <5 years of age\n58,000 –80,000  hospitalizations1,2,3\n100–300 deaths4,5,6~2,000,000  medical encounters1Each year in the United States, RSV leads to approximately*: \n5*Data on the burden of RSV disease in children under 5 are from before the 2023 -2024 RSV season, when RSV prevention products became available in the US.\nReferences: 1) Hall et al, NEJM (2009): https://doi.org/10.1056/NEJMoa0804877 2) McLaughlin et al, J Infect Dis (2022): https://doi.org/10.1093/infdis/jiaa752 3) \nCDC RSV -NET, unpublished data. 4) Thompson et al, JAMA (2003): https://doi.org/10.1001/jama.289.2.179 5) Matias et al, Influenza Other Respi Viruses (2014): \nhttps://doi.org/10.1111/irv.12258 6) Hansen et al, JAMA Network Open (2022): https://doi.org/10.1001/jamanetworkopen.2022.0527\nIn the absence of RSV prevention products: \n•Most infants (68%) are infected in the \nfirst year of life and nearly all (97%) by \nage 2 years2\n•2-3% of young infants are hospitalized for \nRSV3,4,5\n-Highest rates occur in the first months of life, \nand risk declines with increasing age in early \nchildhood3,5\n-79% of children aged <2 years had no \nunderlying medical conditions3\n-All infants are at risk for hospitalizationRSV is the leading cause of hospitalization in infants1\n6\nReferences: 1) Glezen  et al, Arch Dis Child (1986): https://doi.org/10.1001/archpedi.1986.02140200053026  2) Suh et al. JID (2022):  \nhttps://doi.org/10.1093/infdis/jiac120  3) Hall et al, Pediatrics (2013): https://doi.org/10.1542/peds.2013 -0303  4) Langley & Anderson, PIDJ (2011): \nhttps://doi.org/10.1097/INF.0b013e3182184ae7  5) CDC NVSN data6\n2024 –2025  RSV seasonality may be returning to pre -\npandemic trends\nNotes: Report was last updated on  3/26/2025 .\n*All results presented are from nucleic acid amplification tests which represent >90% of the diagnostic tests reported to NRE VSS. The last three weeks of data in 2023 -24 may be less complete. NREVSS is an abbreviation for the National Respiratory and \nEnteric Virus Surveillance System. For more information on NREVSS, please visit National Respiratory and Enteric Virus Surveillance System | CDC .\n**Respiratory syncytial virus types  A and B are not shown separately in this report.\n***The NREVSS surveillance season runs from the first week in July through June of the following year.Percentage* of polymerase chain reaction test results positive for respiratory syncytial virus**, \nby MMWR week — National Respiratory and Enteric Virus Surveillance System, United States, \nJuly 2009 –March 2025\n7\nPre-COVID -19 \npandemic \nseasonality \nshown by grey \nshaded area\nPublic Health Problem - Work Group Interpretation\n•Is RSV -associated disease among infants <8 months of age of public \nhealth importance? \nNoProbably \nNoProbably \nYesYes VariesDon’t \nknow\n8\nEtR Domain: Benefits and Harms\nHow substantial are the desirable anticipated effects?\nHow substantial are the undesirable anticipated effects?\nDo the desirable effects outweigh the undesirable effects?\n9\nGRADE: PICO Question\nPopulation all infants <8 months of age born during or entering their first RSV season\nIntervention clesrovimab\nComparison no immunization \nOutcomesBenefits\n1. RSV-associated medically -attended lower respiratory tract infection (LRTI)\n2. RSV-associated LRTI with hospitalization\n3. RSV-associated LRTI with intensive care unit admission\n4. All-cause medically -attended LRTI\n5. All-cause LRTI with hospitalization \nHarms\n1. Serious adverse events\n10Abbreviations: GRADE: Grading of Recommendations, Assessment, Development and Evaluation\nGRADE: Outcomes, importance, and data sources\nOutcome Importance1 Data sources\nBenefits\n1. RSV -associated medically -attended LRTI Critical Phase 2b/3 RCT2\n2. RSV -associated LRTI with hospitalization Critical Phase 2b/3 RCT2\n3. RSV -associated LRTI with ICU admission Critical Phase 2b/3 RCT2\n4. All -cause medically -attended LRTI Important Phase 2b/3 RCT2\n5. All -cause LRTI with hospitalization Important Phase 2b/3 RCT2\nHarms\n6. Serious adverse events (SAEs) Important Phase 2b/3 RCT2\n1. Three options: Critical; Important but not critical; Not important for decision making\n2. Protocol 004: A Phase 2b/3 Double -Blind, Randomized, Placebo -Controlled Study to Evaluate the Efficacy and Safety of Clesrovimab  in Healthy \nPreterm and Full -Term Infants – described in Zar et al., Open Forum Infectious Diseases (2025): https://doi.org/10.1093/ofid/ofae631.003 ; Sinha, \npresentation to ACIP (2024): https://www.cdc.gov/acip/downloads/slides -2024 -10-23-24/02 -RSV-Mat-Peds -Sinha -508.pdf ; and unpublished data \nfrom manufacturer\nAbbreviations: GRADE: Grading of Recommendations, Assessment, Development and Evaluation | LRTI: Lower respiratory tract infection | \nRCT: randomized controlled trial | ICU: intensive care unit 11\nGRADE Benefits : Efficacy estimates and concerns in \ncertainty  assessment\nOutcome Vaccine efficacy estimate1 \n% (95% CI)Concerns in certainty assessment\nBenefits, through 150 days of follow -up\n1. RSV -associated medically -attended LRTI 60.4 (44.1, 71.9) Not serious (indirectness)2\n2. RSV -associated LRTI with \nhospitalization90.9 (76.2, 96.5) Not serious (indirectness)2\n3. RSV LRTI with ICU admission3100.0 (24.0, 100.0) Serious (imprecision)4\nNot serious (indirectness)2\n4. All -cause medically -attended LRTI 13.1 ( -0.6, 24.8) Serious (imprecision)5\nNot serious (indirectness)2\n5. All -cause LRTI with hospitalization 49.0 (26.7, 64.5) Not serious (indirectness)2\n121. Estimates and 95% CI were estimated from the modified Poisson regression with robust variance method. \n2. Concern for indirectness: the trial excluded infants who were palivizumab -eligible and took place during a season with disrup ted seasonality due to COVID -19. This was \ndeemed not serious.\n3. Outcome was not a trial endpoint and was assessed post -hoc.\n4. Serious concern for imprecision: the number of study participants did not meet optimal information size.\n5. Serious concern for imprecision: the confidence interval containing estimates for which different policy decisions might be considered.\nAbbreviations: GRADE: Grading of Recommendations, Assessment, Development and Evaluation | CI: confidence interval | LRTI: lower respiratory  tract infection | RCT: \nrandomized controlled trial | ICU: intensive care unit \nGRADE Harms : Relative risk of serious adverse events \n(SAEs) and concerns in certainty assessment\nOutcome Relative risk1 (95% CI) Concerns in certainty assessment\nHarms\nSerious adverse events (SAEs)20.93 (0.77, 1.12) Serious (imprecision)3\n1. Relative risk was calculated as the risk of a serious adverse event in the clesrovimab  arm divided by the risk of a serious adverse \nevent in the placebo arm.\n2. Adverse event resulting in death, hospitalization, significant disability, or requiring medical intervention. Serious adverse ev ents \nmay be related or unrelated to the study intervention. \n3. Serious concern for imprecision: too few infants were included in the trial to capture rare events.\n13Abbreviations: GRADE: Grading of Recommendations, Assessment, Development and Evaluation | CI: confidence interval\nSummary of GRADE for clesrovimab\nAbbreviations: LRTI: Lower respiratory tract infection | RCT: randomized control trial | ICU: intensive care unit | serious adverse events Outcome​ Importance Design\n(# of studies)​Findings​ Evidence\ntype​\nBenefits\n1. RSV -associated \nmedically -attended LRTICritical RCT (1)Clesrovimab  is effective in preventing RSV -associated \nmedically -attended LRTIHigh\n2. RSV -associated LRTI \nwith hospitalizationCritical RCT (1)Clesrovimab is effective in preventing RSV -associated LRTI \nwith hospitalizationHigh\n3. RSV -associated LRTI \nwith ICU admissionCritical RCT (1)Clesrovimab is effective in preventing LRTI with ICU \nadmissionModerate\n4. All -cause medically -\nattended LRTIImportant RCT (1)Clesrovimab is not effective in preventing all cause \nmedically -attended LRTIModerate\n5. All -cause LRTI with \nhospitalizationImportant RCT (1)Clesrovimab is moderately effective in preventing all cause \nhospitalization with LRTIHigh\nHarms\n6. Serious adverse events​ Important RCT (1)SAEs were balanced between the clesrovimab group and \nthe placebo groupModerate\n14\nAdditional benefits  of clesrovimab  not included in GRADE: \nEfficacy for RSV -associated medically -attended LRTI and \nhospitalization observed through 180 days\nAbbreviations: LRTI: lower respiratory tract infection | CI: confidence intervalOutcome Follow -up time: 150 days Follow -up time: 180 days\nEvents/\nClesrovimab\n(n/N)Events/\nPlacebo\n(n/N)Vaccine Efficacy % \n(95% CI)Events/\nClesrovimab\n(n/N)Events/\nPlacebo\n(n/N)Vaccine Efficacy % \n(95% CI)\nRSV-associated medically -\nattended LRTI60/2398 74/1201 60.4 (44.1, 71.9) 64/2398 77/1201 59.5 (43.3, 71.1)\nRSV-associated LRTI with \nhospitalization5/2398 27/1201 90.9 (76.2, 96.5) 5/2398 28/1201 91.2 (77.2, 96.6) \n15\nAdditional benefits  of clesrovimab  not included in \nGRADE\n•If approved by FDA and recommended by CDC,  there will be two approved1 \nand recommended2 long -acting monoclonal antibodies for prevention of \nsevere RSV disease in infants\n•Multiple products with different binding sites are beneficial if resistance \nmutations develop to either product\n•Multiple manufacturers in the same market allow for: \n-If one product has insufficient supply in the United States, the other product \nreduces the risk of a shortage.3 \n-Competitive pricing of products may be created by market competition\n1. In July 2023, the Food and Drug Administration (FDA) approved nirsevimab for the prevention of RSV –associated lower respirato ry tract infection  among infants and children aged <24 \nmonths. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761328s000lbl.pdf ; 2. In August 2023, the Advisory Committee for Immunization Practices recommended nirsevimab  \ninfants aged <8 months born during or entering their first RSV season and for infants and children aged 8 –19 months who are at i ncreased risk of severe RSV disease entering their second \nRSV season. https://www.cdc.gov/mmwr/volumes/72/wr/mm7234a4.htm ; 3. https://www.cdc.gov/han/2023/han00499.html16\nAdditional harms  of clesrovimab  not included in \nGRADE: Solicited adverse events (AEs), days 1 –5 post \nimmunization\n•Injection -site and systemic reactions were comparable between the \nclesrovimab  (29.9%) and placebo (30.9%) arms \n-Irritability and somnolence were the most commonly reported solicited AEs\n•Mostly Grade 1 (mild) or 2 (moderate)\n-The proportions of participants with solicited AEs of Grade 3 (severe) were low \n(≤0.2%) in both groups\n-No Grade 4 (potentially life -threatening) solicited AEs\nGrade 1= mild; Grade 2= moderate; Grade 3=severe; Grade 4=potentially life threatening; https://www.fda.gov/media/73679/download17\nAdditional harms  of clesrovimab  not included in \nGRADE: Fever*, days 1 –5 post immunization \nStudy Events*/Clesrovimab\n(n/N)Events*/Placebo\n(n/N)\nProtocol 004 89/2408† (3.7%) 48/1202 (4.0%)\n*Fever defined as a temperature ≥ 100.4 °F\n† Total N=2409; 2408 had temperature data available per communication with manufacturer on March 9, 2025 •Rates of fever were comparable between the clesrovimab  (3.7%) and \nplacebo (4.0%) arms \n18\nWorkgroup interpretation of benefits and harms of \nclesrovimab\nBenefits\n•Efficacious long -acting, monoclonal antibody that can prevent severe RSV \ndisease in young infants during the duration of their first RSV season \n•Second long -acting, monoclonal antibody RSV prevention product would \nmitigate the risk of manufacturing shortages and loss of efficacy due to \nresistance mutations\nHarms\n•Favorable safety profile with no observed increase in serious adverse events, \nlocal or systemic reactions, including fever\n•Rare serious adverse events unlikely to be detected in a trial due to sample \nsize\n19\nBenefits and Harms\n•How substantial are the desirable  anticipated effects?\n-How substantial are the anticipated effects for each main outcome for \nwhich there is a desirable effect?\n20Minimal Small Moderate Large Varies Don’t know\nBenefits and Harms\n•How substantial are the undesirable  anticipated effects?\n-How substantial are the anticipated effects for each main outcome for \nwhich there is an undesirable effect?\nMinimal Small Moderate Large Varies Don’t know\n21\nBenefits and Harms\n•Do the desirable effects outweigh the undesirable effects?\n Favors intervention (clesrovimab)\nProbably favors the intervention (clesrovimab)\nProbably favors the comparison (no immunization)\nFavors the comparison (no immunization)\nUnclear\n22\nEtR Domain: Values\nDo parents and caregivers feel that the desirable effects of clesrovimab  are large \nrelative to the undesirable effects?\nIs there important uncertainty about, or variability in, how much parents and \ncaregivers value the prevention of severe RSV disease? \n23\nParent attitudes about RSV disease\n•38% of respondents believe that their baby would have no symptoms or \nmild symptoms if they got sick with RSV\n•24% expressed uncertainty about the disease severity or treatability if their \nbaby got sick with RSV\n•Despite being unsure or perceiving RSV risk to be low, respondents were \nworried their baby would need to be hospitalized if they got sick with RSV \n(mean response 4 of 5 with 5 being most worried)\nCDC and University of Iowa/RAND survey, unpublished. 523 women who were actively pregnant or pregnant within last 12 months; conducted: 12/2022 —1/2023 24\nFactors that may increase  parental intent to receive RSV \nimmunization products for their infant\n•Trust in pediatrician’s \nrecommendation and fear of RSV \ninfection was associated with \nincreased intent to receive \nnirsevimab1\n•Receiving information about \nmonoclonal antibodies and passive \nimmunization led to a positive impact \n(68%) on willingness to receive the \nimmunization2\nReferences: 1. Hinderstein  et al., Pediatrics (2024): https://10.1542/peds.2024 -067532 ; 2.Lee Mortensen et al., Expert Rev Vaccines (2022): \nhttps://10.1080/14760584.2022.2108799 \n 25\nFactors that may decrease  parental intent to receive RSV \nimmunization products for their infant\n•Parents deferring RSV immunization were concerned about adverse events and \nwanted to wait until the product had been available for longer, wanted more time \nto decide, or trusted their own prevention measures against RSV​1​,2,3,4,5\nReferences: 1. Hinderstein  et al., Pediatrics (2024): https://10.1542/peds.2024 -067532 ; 2.Lee Mortensen et al., Expert Rev Vaccines (2022): \nhttps://10.1080/14760584.2022.2108799 ; 3. Wang et al., Vaccine (2025): https:/10.1016/j.vaccine.2024.126570 ; 4.Zornoza  Moreno et al., Hum Vaccin  Immunother  (2024): \nhttps://10.1080/21645515.2024.2357439 ; 5.Ocana  de Sentuary  et al., EClinicalMedicine  (2025): https://10.1016/j.eclinm.2024.102986 26\n50%  of women 18 -49 years who have an infant <8 months received \nnirsevimab for their infant, February  2025, United States\n*Receipt of RSV vaccination during pregnancy was assessed by the NIS –ACM questionnaire among women 18 –49 years who reported havi ng an infant born since October 1, 2024. For infants born April 1, 2024, through September 30, 2024, maternal RSV \nvaccination was not assessed, and these infants were assumed to be protected against RSV only if infant was reported to have received nirsevimab. The estimates of receipt of RSV vaccination during pregnancy for infants born since April 1, 2024 are not a n \nassessment of maternal RSV vaccination coverage among pregnant women eligible for vaccination as shown with the Vaccine Safety Datalink , as they are based on all infants eligible for nirsevimab or maternal vaccination rather than eligible pregnancies\n†Estimates of nirsevimab receipt by infants born since April 1, 2024, include those who were born shortly before or are enter ing their first RSV season and do not account for the mother's RSV vaccination status during pregnancy\n‡Intent for nirsevimab receipt is assessed among infants who had not received nirsevimab and whose mother did not receive RSV  vaccination during pregnancy. Estimates of nirsevimab intent among women interviewed in August and September 2024 \nincluded all women who reported having an infant <8 months, and could include infants born in February and March 2024.\nData Source: National Immunization Survey – Adult COVID Module https://www.cdc.gov/rsvvaxview/dashboard/nirsevimab -coverage -infants.html27Infant protection against RSV by maternal RSV vaccination* or receipt of nirsevimab †, and \nintent‡ for nirsevimab receipt by women aged 18 –49 years who have an infant <8 months \nduring the RSV season (born since April 1, 2024), February, United States  \nMother received RSV vaccination \nduring pregnancy\nInfant received nirsevimab\n \nDefinitely will get nirsevimab for \ninfant\nProbably will get nirsevimab for \ninfant or unsure  \nProbably or definitely will not get \nnirsevimab for infant\n\nNirsevimab uptake may be higher in settings of increased \naccess\nReferences: 1. Puckett et al., Hosp Pediatr  (2025 ): https:// 10.1542/hpeds.2024 -008070.\n71% of newborns received nirsevimab at a US \nbirthing center when it was universally offered1\n28\n•Do parents and caregivers feel that the desirable effects of clesrovimab  \nare large relative to the undesirable effects?Values\nNoProbably \nNoProbably \nYesYes VariesDon’t \nknow\n29Minority opinion Majority opinion\nValues\n•Is there important uncertainty about, or variability in, how much how \nmuch parents and caregivers value the prevention of severe RSV \ndisease ?\nImportant uncertainty or variability\nProbably important uncertainty or variability\nProbably not important uncertainty or variability\nNo important uncertainty or variability\nNo known undesirable outcomes\n30Minority opinion Majority opinion\nEtR Domain: Acceptability\nIs clesrovimab  acceptable to key stakeholders?\n31\nPediatrician attitudes about nirsevimab may provide insight \ninto their potential attitudes about clesrovimab  \n*Porter Novelli  View Health Care Practitioner survey was conducted from October 2 -10, 2024, among 200 U.S. pediatricians who reported offering at least some routine pediatric vaccines \nto patients\nKang et al, CDC (2024); https://www.cdc.gov/rsvvaxview/publications/rsv -immunization -survey -2024.html329194.595.596.5\n74.543\n210.50.5\n0% 20% 40% 60% 80% 100%I feel comfortable co-administering nirsevimab and one or more\nvaccines to my pediatric patients in one visit.I feel confident discussing and recommending nirsevimab\nimmunization with my patient's parents/caregiversNirsevimab is effective against severe RSV disease in infantsNirsevimab is safe for infantsPediatrician attitudes about nirsevimab, Pediatrician survey*, October 2024, n=200\nStrongly agree or agree\nNeither agree nor disagree\nDisagree or strongly disagree\n•77% of pediatricians reported that their practice had ever offered nirsevimab\n•The majority of pediatricians agreed that nirsevimab is safe for infants and effective against severe \ndisease in infants\nRSV prevention through long -acting, monoclonal \nantibodies endorsed by national organizations\n•Nirsevimab is recommended by\n-American Academy of Pediatrics1\n-American Academy of Family Physicians2\n-National Foundation for Infectious Diseases3 \n1)https://publications.aap.org/redbook/resources/25379/AAP -Recommendations -for-the-Prevention -of-RSV?autologincheck=redirected\n2)https://www.aafp.org/news/health -of-the-public/rsv -antibody -aafp -approval.html\n3)https://www.nfid.org/resource/contagious -chronicles -updated -recommendations -for-respiratory -season/33\nAcceptability\n•Is clesrovimab  acceptable to key stakeholders?\nNo Probably No Probably Yes Yes Varies Don’t know\n34Minority opinion Majority opinion\nEtR Domain: Feasibility\nIs clesrovimab  feasible to implement among all infants <8 months of age \nborn during or entering their first RSV season?\n35\nClesrovimab  storage, handling, and administration\n•Clesrovimab  storage, handling, and administration is anticipated to be similar to \nother routine immunizations for children\n•Administered as an intramuscular injection using a single -dose, prefilled syringe\n•Stored at refrigerator temperature (2 °C to 8 °C) \n•May be kept at room temperature between 68 °F to 77 °F (20 °C to 25 °C) for a \nmaximum of 48 hours. \n-After removal from the refrigerator, must be used within 48 hours or discarded\n•Dosage is 0.7 mL for all infants born during or entering their first RSV season \nregardless of weight\n•Can be administered simultaneously with other vaccines \n36\nImplementation and access \n•The Vaccines for Children (VFC) program is a federally funded program that \nprovides immunizations at no cost to children who might not otherwise be \nimmunized because of inability to pay.1\n-If ACIP votes to include clesrovimab  in VFC, it will be  the second monoclonal \nantibody to be included in the VFC program.\n•Implementation pros and cons: \n-Pro: Clesrovimab  is a single dose regardless of weight\n-Con: Stocking clesrovimab  may be challenging for providers who also need  to \nstock nirsevimab for high -risk children 8 through 19 months entering their second \nRSV season and prefer to stock a single RSV monoclonal antibody\n1. CDC. Vaccines for Children .https://www.cdc.gov/vaccines -for-children/about/index.html37\n*Respondents were instructed to select up to 3 response categories\n** Private stock of nirsevimab for practices participating in the VFC (Vaccines for Children) program \n*** Challenges knowing whether infant received nirsevimab at a birthing hospital\nYoonjae Kang, MPH; Fan Zhang, MD; Tara M Vogt, PhD, MPH; https://www.cdc.gov/rsvvaxview/publications/rsv -immunization -survey -2024.html44\n33.5\n30.5\n30.5\n24.5\n20\n20\n15.5\n7.5\n8.547.4\n38.3\n26\n27.9\n28.6\n21.4\n20.1\n13\n7.8\n7.832.6\n17.4\n45.7\n39.1\n10.9\n15.2\n19.6\n23.9\n6.5\n10.9Parent/caregiver concerns around nirsevimab safety\nChallenges knowing maternal RSV vaccination status to determine infant eligibility\nFinancial burden in purchasing of nirsevimab**\nChallenges with reimbursement from private health insurance plans\nLack of demand from parents/caregivers\nChallenges deterimining infant eligibility***\nParent/caregiver concerns around nirsevimab effectiveness\nChallenges with Medicaid reimbursement\nSupply/stock issues\nPractice does not have or does not anticipate having challenges in offering nirsevimab\nAll pediatricians (n=200) Pediatricians whose practice had ever offered nirsevimab (n=154) Pediatricians whose practice had never offered nirsevimab (n=46)Frequency of main challenges* pediatricians reported or \nanticipated in offering nirsevimab, Pediatrician survey, October \n2024, n=200\n38\nBirthing hospital barriers to monoclonal antibody \nadministration\n•In a series of CDC Learning Collaborative calls hosted by the Association for \nImmunization Managers on nirsevimab administration in birthing \nhospitals, common barriers included:  \n-Determining maternal RSV vaccination status\n-Storage and handling\n-Billing\n-Cost of nirsevimab \n-Nirsevimab supply/shortages\n-Determining a newborn’s VFC eligibility \n-Documenting nirsevimab receipt and care coordination \n-VFC requirements can be difficult to implement and enrollment is burdensome\nVFC: Vaccines for Children39\nFeasibility\n•Is clesrovimab  feasible to implement among all infants <8 months of \nage born during or entering their first RSV season?\n40Minority opinion Majority opinionNo Probably No Probably Yes Yes Varies Don’t know\nEtR Domain: Resource Use\nIs clesrovimab  a reasonable and efficient allocation of resources?\n41\n1. Estimates provided by an updated UM -CDC model, where updates included VE and cost/dose. Original model and methods described her e: David W. \nHutton, Lisa A. Prosser, Angela M. Rose, Kerra Mercon ,Ismael R. Ortega -Sanchez, Andrew J. Leidner, Meredith L. McMorrow, Katherine E. Fleming -Dutra, Mila \nM. Prill, Jamison Pike, Jefferson M. Jones; Cost -Effectiveness of Nirsevimab for Respiratory Syncytial Virus in Infants and Youn gChildren. Pediatrics December \n2024; 154 (6): e2024066461. 10.1542/peds.2024 -066461.\n2. Clesrovimab  has 50% coverage, and includes 50% palivizumab use for eligible high -risk babies that do not get clesrovimab  \n3. “No RSV immunizations for most infants \" means the only RSV immunization is palivizumab for eligible high -risk infants\nAbbreviations: ED: emergency department | ICU: intensive care unit | QALY: quality adjusted life yearRSV-associated outcomes averted: 50% coverage with \nclesrovimab  among an annual US birth cohort1 \nComparison Outpatient \nVisits \nAvertedED Visits \nAvertedHospital \nAdmissions \nAvertedICU \nAdmissions \nAvertedDeaths \nAvertedQALYs \nGained\nClesrovimab2 vs. no RSV \nimmunizations for most \ninfants3121,022 43,480 20,198 4,444 20 3,413 \n42\nIncremental cost effectiveness ratios (ICERs):  50% \ncoverage with clesrovimab  among an annual US birth \ncohort1 \nComparison $/Outpatient \nVisit Averted$/ED Visit \nAverted$/Hospital \nAdmission \nAverted$/ICU \nAdmission \nAverted$/Death \nAverted$/QALY \nGained\nClesrovimab2 vs. no \nRSV i mmunizations for \nmost infants32,948 8,207 17,666 80,300 17,666,032 104,543 \n1. Estimates provided by an updated UM -CDC model, where updates included VE and cost/dose. Original model and methods described here: Hutton et al, \nPeds (2024);.https://doi.org/10.1542/peds.2024 -066461.\n2.  Clesrovimab  has 50% coverage, and includes 50% palivizumab use for eligible high -risk babies that do not get clesrovimab  \n3. “No RSV immunizations for most infants \" means the only RSV immunization is palivizumab for eligible high -risk infants\nAbbreviations: ED: emergency department | ICU: intensive care unit | QALY: quality adjusted life year43\nOne -way sensitivity analysis: 50% coverage with \nclesrovimab  among an annual US birth cohort1   \n$0 $50,000 $100,000 $150,000 $200,000 $250,000\nDisease-Specific Inpatient Costs (per Inpatient Case)\nRSV QALYS Lost\nClesrovimab cost/dose\nProportion of Outpatient Visits With an LRTI Diagnosis Age 0-5 Months\nProportion of Hospitalizations With an LRTI Diagnosis Age 0-5 Months\nProportion of Outpatient Visits With an LRTI Diagnosis Age 6-11 Months\nFraction Receiving Palivizumab Natural History\nOutpatient Efficacy\nRSV Mortality Per Hospitalization Age 0-5 Months\nEfficacy 6-10 monthsIncremental Cost -Effectiveness Ratio ($/QALY gained)\nLow High\n1. Estimates provided by an updated UM -CDC model, where updates included VE and cost/dose. Original model and methods described her e: David W. Hutton, Lisa A. Prosser, Angela M. \nRose, Kerra Mercon ,Ismael R. Ortega -Sanchez, Andrew J. Leidner, Meredith L. McMorrow, Katherine E. Fleming -Dutra, Mila M. Prill, Jamison Pike, Jefferson M. Jones; Cost -Effectiveness \nofNirsevimab for Respiratory Syncytial Virus in Infants and Young Children. Pediatrics December 2024; 154 (6): e2024066461. 10. 1542/peds.2024 -066461.\nAbbreviations: QALY : quality adjusted life year 44\nMerck1 and University of Michigan – CDC2 Model \nComparison\n•University of Michigan/CDC Model \n-$/QALY gained: $ 104,543 (assumes $457/dose) \n•Merck Model \n-$/QALY gained: $7,372 -$42,691 (assumes $423 - $493/dose); $ 36,636 (assumes \n$457/dose) \n•Key differences in inputs\n-Initial efficacy and waning trajectory\n-Medical costs \n-Adverse events \n1. Klodeta Kura, John C Lang, Dawei  Wang, et al. Merck’s technical report: Cost -effectiveness analysis of clesrovimab  use in infants in the United states. (Version submitted to CDC \nand ACIP for review, January 27, 2025)\n2. Estimates provided by an updated UM -CDC model, where updates included vaccine efficacy, vaccine efficacy waning trajectory, a nd cost/dose. Original model and methods \ndescribed here: David W. Hutton, Lisa A. Prosser, Angela M. Rose, Kerra Mercon ,Ismael R. Ortega -Sanchez, Andrew J. Leidner, Meredith L. McMorrow, Katherine E. Fleming -\nDutra, Mila M. Prill, Jamison Pike, Jefferson M. Jones; Cost -Effectiveness of Nirsevimab for Respiratory Syncytial Virus in Infa nts and Young Children. Pediatrics December 2024; \n154 (6): e2024066461. 10.1542/peds.2024 -066461.\nAbbreviations: QALY:  quality adjusted life year 45\nResource use summary\n•Clesrovimab  cost $104,543 per QALY gained in the base case, with \nsensitivity analyses ranging from cost saving to $215,000/QALY\n•Cost effectiveness models sensitive to\n-Inpatient costs \n-Clesrovimab  cost/dose \n-QALYs lost due to RSV illness\nAbbreviations: QALY : quality adjusted life year 46\nResource Use \n•Is clesrovimab  use among all infants under 8 months of age born during or \nentering their first RSV season a reasonable and efficient allocation of \nresources with an estimated cost of $458 on average ($365 VFC / $560 \nother) per dose? \n47No Probably No Probably Yes Yes Varies Don’t know\nMinority opinion Majority opinion\nAbbreviations: VFC:  Vaccines for Children  \nEtR Domain: Equity\nWhat would the impact of clesrovimab  be on health equity for infants?\n48\nAdjusted population -based hospitalization  rates  among \ninfants <6 months old with laboratory -confirmed RSV by race \nand ethnicity, RSV -NET, 2018 –2019 to 2024 –2025\nRSV-NET: unpublished data. Surveillance was conducted during October –April for the 2018 –19 and 2019 –20 seasons and during May –April for 2021 –22 onwards. Rates were \nadjusted for RSV testing practices and test sensitivity. Black, White, Asian/Pacific Islander children were categorized as no n-Hispanic; Hispanic children could be of any \nrace.*2020 –21 season experienced limited to no RSV circulation **2024 –25 data available through February 1, 2025 050010001500200025003000\n2018–2019 2019–2020 2020–2021* 2021–2022 2022–2023 2023–2024 2024–2025**Rate per 100,000 population\nNon-Hispanic Black Hispanic Non-Hispanic White Non-Hispanic Asian or Pacific Islander\nHospitalization rates among infants <6 months old differ by race and ethnicity \nbut this difference varies by seasonRSV immunization products availableRSV circulation impacted by COVID -19 pandemic\n49\nAdjusted population -based ICU admission  rates  among \ninfants <6 months old with laboratory -confirmed RSV by race \nand ethnicity, RSV -NET, 2018 –2019 to 2024 –2025\nRSV-NET: unpublished data. Surveillance was conducted during October –April for the 2018 –19 and 2019 –20 seasons and during May –April for 2021 –22 onwards. Rates were \nadjusted for RSV testing practices and test sensitivity. Black, White, Asian/Pacific Islander children were categorized as no n-Hispanic; Hispanic children could be of any race. \n*2020 –21 season experienced limited to no RSV circulation; **2024 –25 data available through February 1, 2025 ICU admission rates among infants <6 months old differ by race and ethnicity \nbut this difference varies by seasonRSV immunization products availableRSV circulation impacted by COVID -19 pandemic\n01002003004005006007008009001000\n2018–2019 2019–2020 2020–2021* 2021–2022 2022–2023 2023–2024 2024–2025**Rate per 100,000 population\nNon-Hispanic Black Hispanic Non-Hispanic White Non-Hispanic Asian or Pacific Islander\n50\nRSV rates of severe disease by race and ethnicity\n•RSV hospitalization rates were up to 7x higher among Alaska Native and American \nIndian children compared to children aged less than 1 year1\n-This study was limited to specific populations and might not be broadly representative of risk in all \nAlaska Native and American Indian children \n•National studies of death certificates found higher rates among non -Hispanic Black \nand Hispanic children compared to non -Hispanic White children2\n•Hospitalization rates using NVSN data have shown mixed results3\n-Several studies have shown no differences by race or ethnicity4-7\n-Even when significant, relative risk for non -Hispanic Black and Hispanic children mildly increased \ncompared to non -Hispanic, White children (e.g., relative risk of 1.2 -2.2)6-7\n1. Atwell et al. 2023 Aug 1;152(2):e2022060435\n2. Hansen J Infect Dis 2022 Aug 15;226(Suppl 2):S255 -S266\n3. NVSN analyses compared incidence rates of non -Hispanic Black, non -Hispanic White, and \nHispanic children\nAbbreviations: NVSN: New Vaccine Surveillance Network 4. Hall Pediatrics 2013 Aug;132(2):e341 -8\n5. Hall NEJM 2009;360(6):588 –598\n6. Iwane  Pediatrics 2004 Jun;113(6):1758 -64, findings differed by age group\n7. Rha Pediatrics 2020 Jul;146(1):e20193611, findings differed by age group51\nEquity\n•What would be the impact of clesrovimab  on health equity?\nReduced\nProbably reduced\nProbably no impact\nProbably increased\nIncreased\nVaries\nDon’t know\n52Minority opinion Majority opinion\nEtR Summary\n53\nWork group considerations and interpretation\n•Phase 2b/3 trial demonstrated high efficacy for prevention of severe RSV disease \nthrough 150 days\n•Serious adverse events appeared balanced between the clesrovimab and placebo \narms, however rare adverse events are unlikely to be detected in a trial of this size\n•Work group discussion also highlighted:\n•Clesrovimab has demonstrated a shorter half -life than nirsevimab (421vs 712days), \nhowever efficacy against severe RSV appeared sustained through  150 days\n• Clesrovimab and nirsevimab trial outcomes had different definitions ​, making direct comparisons \nin efficacy difficult \n1. Maas et al. https://www.sciensano.be/sites/default/files/pk_sna_and_efficacy_against_rsv_malri_from_a_phase_1b2a_study_of_the_monoclonal_ antibody_clesrovimab_mk -1654_in_infants.pdf   \n2. https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761328s000lbl.pdf54\n•The work group highlighted the benefits of multiple RSV antibody products \nand multiple manufacturers, including:\n-If RSV develops resistance to one product or one product has insufficient supply, \nanother is available\n-Potential for decrease in price\n•The leading cause of hospitalization in infants (RSV) can be prevented \nthrough immunization. However, for RSV immunizations to have public \nhealth impact, they must be administered early:\n-For infants born outside  the RSV season, high uptake prior to season onset is \nessential\n-For infants born during  the RSV season, administration should be within the first \nweek of life - ideally during the birth hospitalizationWork group considerations and interpretation, \ncontinued\n55\nEvidence to Recommendations Framework\nSummary\nBalance of\nconsequencesUndesirable\nconsequences\nclearly\noutweigh\ndesirable\nconsequences\nin most settingsUndesirable\nconsequences\nprobably\noutweigh\ndesirable\nconsequences\nin most settingsThe balance\nbetween\ndesirable \nand undesirable\nconsequences\nisclosely\nbalanced or\nuncertainDesirable\nconsequences\nprobably\noutweigh\nundesirable\nconsequences\nin most settingsDesirable\nconsequences\nclearly\noutweigh\nundesirable\nconsequences\nin most settingsThere \nisinsufficient\nevidence \ntodetermine \nthebalance of\nconsequences\n56•What is the balance between the desirable effects relative to the undesirable effects?\nEvidence to Recommendations Framework\nSummary\nType of\nrecommendationWe do not \nrecommend the \ninterventionWe recommend \ntheintervention for \nindividuals based on \nshared \nclinical decision -\nmakingWe recommend \ntheintervention\n57•Should clesrovimab  be recommended for all infants <8 months of age born during or \nentering their first RSV season?\nAcknowledgements\nJefferson Jones\nMila Prill \nMeredith McMorrow \nRuth Link -Gelles\nMonica Godfrey \nMichael Melgar\nAmadea Britton\nAmber Kautz\nLauren Roper \nMonica Patton\nFiona Havers \nBen Silk Amber Winn\nAlexa Churan\nMelissa Shah\nAmanda Payne \nDavid Hutton \nJamison Pike \nAndrew Leidner \nIsmael Ortega -Sanchez \nNaomi Tepper\nHeidi Moline\nFatimah Dawood\nJenny MiluckyCoronavirus and Other \nRespiratory Viruses Division\nImmunization Services Division\nRSV-NET \nNIS-ACM \n58\n59\nGRADE: Clesrovimab  \n60\nEvidence retrieval, conducted as of December 3, 2024\nRecords screened\n(n=182)\nStudies or papers  \nirrelevant\n(n=161)Full text studies \nassessed for eligibility\n(n=21)Studies excluded\n(n=20)\n9 trial description \n5 wrong population\n2 wrong intervention\n1 wrong comparator\n3 wrong outcomesRecords included in \nevidence synthesis \n(n=1)\n*Medline (OVID), Embase (OVID), Cochrane Library, CINAHL ( EbscoHost ), Scopus, clinicaltrials.govAdditional records identified \nthrough other sources\n(n = 2)\n61Records identified through \ndatabase searching\n(n = 180)*\nProtocol 004: Phase 2b/3, double -blinded, placebo -\ncontrolled trial\n•3,614 healthy preterm infants (gestational age ≥29 weeks to <35 weeks) and full -term \ninfants (GA ≥35 weeks) born during or entering their first RSV season\n-Randomized 2:1 (2,411 clesrovimab , 1,203 placebo)\n-Enrolled at birth up to 1 year (median age at randomization: 3.1 months) \n•Multi -country: Argentina, Belgium, Canada, Chile, China, Colombia, Denmark, Finland, \nFrance, Italy, Japan, Korea, Malaysia, Mexico, Peru, Philippines, Poland, Thailand, Turkey, \nUK, USA, South Africa\n-Over 2/3 of infants enrolled were from the Northern Hemisphere\n•Primary efficacy outcomes followed for 150 days, safety, and pharmacokinetics\n-Secondary efficacy outcomes with follow -up through 150 and 180 days\n62\nGRADE evidence type\n•High certainty: We are very confident that the true effect lies close to that \nof the estimate of the effect.\n•Moderate certainty: We are moderately confident in the effect estimate: \nThe true effect is likely to be close to the estimate of the effect, but there is \na possibility that it is substantially different.\n•Low certainty: Our confidence in the effect estimate is limited. The true \neffect may be substantially different from the effect estimate.\n•Very low certainty: We have very little confidence in the effect estimate. \nThe true effect is likely to be substantially different from the estimate of the \neffect .\nNOTE: Evidence type is not measuring the quality of individual studies, but how much certainty we have in the estimates \nof effect across each outcome.\n63\nGRADE evidence type\n•Initial evidence type (certainty level) determined by study design\n-Initial evidence is high  certainty: A body of evidence from randomized controlled \ntrials\n-Initial evidence is low certainty: A body of evidence from observational studies\n•Evidence type may be downgraded due to risk of bias, inconsistency, indirectness, \nand imprecision. Evidence type may be upgraded or downgraded due to other \nconsiderations including publication bias or indications of dose -response gradient, \nlarge or very large magnitude of effect, and opposing residual confounding. \nNOTE: Evidence type is not measuring the quality of individual studies, but how much certainty we have in the estimates \nof effect across each outcome.\n64\nBenefits \n65\nCase definitions for benefits  \nOutcomes ≥ 1 signs/symptomsAND ≥ 1 indicator of \nLRTI/severityRSV-positive RT -PCR NP \nsampleSetting\n1. RSV -associated \nmedically -attended LRTIAt least one sign/symptom \non examination:\n• Cough\n• Difficulty \nbreathingAt least one of:\n• Rales/crackles\n• Wheezing\n• Chest wall \nindrawing/retra\nctions\n• Hypoxemia*\n• Tachypnea**\n• Dehydration \ndue to \nrespiratory \nsymptomsRequired Outpatient or inpatient \nclinical setting \n2. RSV -associated LRTI with \nhospitalizationInpatient clinical setting \n3. RSV -associated LRTI with \nICU admissionInpatient clinical setting \n4. All -cause medically -\nattended LRTINot required Outpatient or inpatient \nclinical setting \n5. All -cause LRTI -associated \nhospitalization Inpatient clinical setting \n* Hypoxemia was defined as SpO2 <95% on room air at sea level, <92% on room air at altitude≥1800 m. In room air - oxygen saturation <95% at altitudes \n≤1800 meters or <92% at altitudes >1800 meters\n** Tachypnea was defined as RR≥60 breaths per minute for <2 months of age;≥50 breaths per minute for 2 to 12 months of age; or≥4 0 breaths per minute \nfor >12 to 24 months of age\nAbbreviations: LRTI: lower respiratory tract infection | ICU: intensive care unit | RT -PCR: reverse transcription polymerase chain reaction | N P: \nnasopharyngeal  | RR: respiratory rate66\nOutcome 1: RSV -associated medically -attended LRTI1 \nthrough 150 days of follow -up \nStudy Events1/Clesrovimab\nn/N (%)Events1/Placebo\nn/N (%) Efficacy2\n(95% CI)\nProtocol 004 60/23983 (2.5%) 74/12013 (6.2%) 60.4% (44.1, 71.9)\n1.Defined by the presence of the following seen in an outpatient or inpatient clinical setting: cough or difficulty breathing A ND ≥ 1 indicator of LRTI or \nseverity (wheezing, chest wall in -drawing/retractions, rales/crackles, hypoxemia, tachypnea, dehydration due to respiratory symp toms); AND RSV \npositive reverse transcriptase -polymerase chain reaction (RT -PCR) nasopharyngeal (NP) sample. \n2.Estimates and 95% CI were estimated from the modified Poisson regression with robust variance method. The model included the following \ncovariates: hemisphere at randomization, gestational age group and age group at randomization. The lower bound of the 95% CI was >25%, meeting \nthe statistical criterion for success.\n3.Patients were randomized 2:1 to the clesrovimab  and placebo arms. \nAbbreviations: LRTI: lower respiratory tract infection | CI: confidence interval 67\nGRADE: RSV -associated medically -attended LRTI \nthrough  150 days of follow -up (n=1 study)\n•Measure of effect\n-Efficacy: 60.4% (95% CI: 44.1, 71.9)\n•Absolute risk (using 23.1% seasonal incidence1): 140 fewer cases per 1,000 immunized (166 fewer \nto 102 fewer)\n–Number needed to immunize: 7 (6 to 10)\n•Absolute risk (using 11.0% seasonal incidence2): 66 fewer cases per 1,000 immunized (79 fewer to \n49 fewer)\n–Number needed to immunize: 15 (13 to 20)\n•Absolute risk (using 6.2% seasonal incidence [phase 2b/3 trial placebo arm]): 37 fewer cases per \n1,000 immunized (44 fewer to 27 fewer)\n–Number needed to immunize: 27 (22 to 37)\n•Concerns in certainty assessment\n-Not serious (indirectness):  trial excluded infants who were palivizumab eligible \n•Final evidence type: High\n1. Lively 2019 JPIDS , 5 years from 3 NVSN sites from Nov -Apr season, included if with acute respiratory infection (ARI, not restricted to LRTI).  2.  Assumes 47.5% \nof ARI are LRTI ( Rainisch  2020 Vaccine ) \nAbbreviations: LRTI: lower respiratory tract infection | CI = confidence interval 68\nOutcome 2: RSV -associated LRTI with hospitalization1 \nthrough 150 days of follow -up \nStudy Events1/Clesrovimab\nn/N (%)Events1/Placebo\nn/N (%)Efficacy2\n(95% CI)*\nProtocol 004 5/23983 (0.2%) 27/12013 (2.2%) 90.9% (76.2, 96.5)\nAbbreviations: LRTI: lower respiratory tract infection | CI: confidence interval 1.Defined by the presence of the following seen in an inpatient clinical setting:  cough or difficulty breathing AND  ≥ 1 indicator of LRTI (rhonchi, \nrales/crackles, wheezing) AND ≥1 indicator of severity (chest wall indrawing/retractions, hypoxemia, tachypnea, dehydration d ue to respiratory \nsymptoms); AND RSV positive reverse transcriptase -polymerase chain reaction (RT -PCR) nasopharyngeal (NP) sample. \n2.Estimates and 95% CI were estimated from the modified Poisson regression with robust variance method. \n3.Patients were randomized 2:1 to the clesrovimab  and placebo arms. \n69\nGRADE: RSV-associated LRTI with hospitalization \nthrough 150 days of follow -up (n=1 study)\n•Measures of effect\n-Efficacy: 90.9% (95% CI: 76.2, 96.5)\n-Absolute risk (using 1.3% seasonal incidence*): 12 fewer cases per 1,000 \nimmunized (13 fewer to 10 fewer)\n•Number needed to immunize: 83 (77 to 100)\n-Absolute risk (using 2.2% seasonal incidence [phase 2b/3 trial placebo arm]): 20 \nfewer cases per 1,000 immunized (22 fewer to 17 fewer)\n•Number needed to immunize: 50 (45 to 59)\n•Concerns in certainty assessment\n-Not serious (indirectness): trial excluded infants who were palivizumab eligible \n•Final evidence type: High\n*NVSN data 2016 -2020 (unpublished), included if with acute respiratory infection\nAbbreviations: LRTI: lower respiratory tract infection  70\nOutcome 3: RSV -associated LRTI with ICU admission1 \nthrough 150 days of follow -up \nAbbreviations:  LRTI: lower respiratory tract infection | CI: confidence interval | ICU: intensive care unit | PICU: pediatric intensive care unit | NICU: \nneonatal intensive care unitStudy Events1/Clesrovimab\n(n/N)Events1/Placebo\n(n/N)Efficacy2 \n(95% CI)\nProtocol 004 0/23983 44/12013100% (24, 100)\n1.Defined as hospital admission for respiratory illness AND RSV -positive RT -PCR nasopharyngeal (NP) sample AND with evidence of adm ission in ICU in the associated serious \nadverse event (SAE) narrative by looking for one or more of these following key terms: ICU, PICU, NICU, mechanical ventilatio n, ventilator, intubation, intubated, intensive \ncare, intensive care unit, intensive treatment unit, critical care unit. \n2.Estimates and 95% CI were estimated by an exact method. \n3.Patients were randomized 2:1 to the clesrovimab  and placebo arms. \n4.Onset of all 4 cases were prior to day 150.  No cases occurred between days 150 -180.\n71\nGRADE: RSV-associated LRTI with ICU admission \nthrough 150 days of follow -up (n=1 study)\n•Measures of effect\n-Efficacy: 100% (95% CI: 24, 100)\n-Absolute risk  (using 0.33% seasonal incidence [phase 2b/3 trial placebo arm]) : 330 \nfewer per 100,000 (from 79 to 330 fewer) \n•Number needed to immunize: 303 (from 303 to 1,265)\n•Concerns in certainty assessment\n-Not serious (indirectness): trial excluded infants who were palivizumab eligible \n-Serious (imprecision): number of study participants did not meet optimal \ninformation size for this outcome\n•Evidence type: Moderate\n72Abbreviations:  ICU: intensive care unite | LRTI: lower respiratory tract infection | CI: confidence interval \nOutcome 4:  All-cause medically attended LRTI1 \nthrough  150 days of follow -up \nStudy Events1/Clesrovimab\nn/N (%)Events1/Placebo\nn/N (%)Efficacy2\n(95% CI)\nProtocol 004 526/23983 (21.9%) 296/12013 (24.6%) 13.1% ( -0.6, 24.8)\nAbbreviations: LRTI: lower respiratory tract infection | CI: confidence interval 1.Defined as  outpatient and inpatient medically -attended LRTI due to any cause, defined by the presence of the following seen in an outpatie nt or \ninpatient clinical setting: cough or difficulty breathing AND 1 or more of the following: wheezing, chest wall in -drawing/retrac tions, rales/crackles, \nhypoxemia, tachypnea, dehydration due to respiratory symptoms.\n2.Estimates and 95% CI were estimated from the modified Poisson regression with robust variance method. \n3.Patients were randomized 2:1 to the clesrovimab  and placebo arms. \n73\nGRADE: All -cause medically -attended LRTI through  150 \ndays of follow -up (n=1 study)\n•Measures of effect\n-Efficacy: 13.1% (95% CI: -0.6, 24.8)\n-Absolute risk (using 24.6% seasonal incidence in phase 2b/3 controls): 26 fewer \ncases per 1,000 vaccinated (61 fewer to 1 more)\n•Number needed to immunize: 38 (16 to *)\n•Concerns in certainty assessment\n-Not serious (indirectness): trial excluded infants who were palivizumab eligible \n-Serious (imprecision): width of the confidence interval contains estimates for \nwhich different policy decisions might be considered \n•Evidence type: Moderate\n*Upper bound of the confidence interval could not be calculated. \nAbbreviations: LRTI: lower respiratory tract infection | | CI: confidence interval 74\nOutcome 5: All-cause hospitalization with LRTI1 \nthrough 150 days of follow -up \nStudy Events1/Clesrovimab\nn/N (%)Events1/Placebo\n(n/N)Efficacy2\n(95% CI)\nProtocol 004 60/23983 (2.5%) 58/12013 (4.8%) 49.0% (26.7, 64.5)\n1.Defined by the presence of the following seen in an inpatient clinical setting: cough or difficulty breathing AND ≥ 1 indicator of LRTI (rhonchi, \nrales/crackles, wheezing) AND ≥1 indicator of severity (chest wall indrawing/retractions, hypoxemia, tachypnea, dehydration d ue to respiratory \nsymptoms)\n2.Estimates and 95% CI were estimated from the modified Poisson regression with robust variance method. \n3.Patients were randomized 2:1 to the clesrovimab  and placebo arms. \n75Abbreviations: LRTI: lower respiratory tract infection | CI: confidence interval | RT -PCR: reverse transcription polymerase chain reaction | IC U: intensive \ncare unit | PICU: pediatric intensive care unit | NICU: neonatal intensive care unit \nGRADE: All -cause hospitalization with LRTI through \n150 days of follow -up (n=1 study)\n•Measures of effect\n-Efficacy: 49.0% (95% CI: 6.7, 64.5)\n-Absolute risk (using 4.1% seasonal incidence [phase 2b/3 trial controls]): 20 fewer \ncases per 1,000 immunized (27 fewer to 11 fewer)\n•Number needed to immunize: 50 (37 to 91)\n•Concerns in certainty assessment\n-Not serious (indirectness): trial excluded infants who were palivizumab eligible \n•Evidence type: High\nAbbreviations: LRTI: lower respiratory tract infection | CI: confidence interval 76\nHarms \n77\nOutcome 6: Serious adverse events (SAEs)1 through \n365 days post -dose\nStudy Events1/Clesrovimab\nn/N (%)Events1/Placebo\nn/N (%)RR\n(95% CI)\nProtocol 004 278/24092 (11.5%) 149/12022 (12.4%) 0.93 (0.77, 1.12)\nAbbreviations: RR: risk ratio | CI: confidence interval 1.Defined as an adverse event resulting in death, hospitalization, significant disability, or requiring medical intervention care, intensive care unit, \nintensive treatment unit, critical care unit. Serious adverse events may be related or unrelated to the study intervention. \n2.Patients were randomized 2:1 to the clesrovimab and placebo arms. \n78\nGRADE: Serious adverse events  through 365 days \npost -dose  (n=1 study)\n•Measures of effect\n-Relative Risk: 0.93 (95% CI: 0.77 to 1.12)\n-Absolute risk: 9 fewer cases per 1,000 immunized (29 fewer to 16 more)\n•Concerns in certainty assessment\n-Serious (imprecision): T oo few infants included in the trial to capture rare serious \nadverse events\n•Evidence type: Moderate\n79Abbreviations: CI: confidence interval \nSummary of GRADE for clesrovimab\nOutcome​ Importance Design\n(# of studies)​Findings​ Evidence\ntype​\nBenefits\n1. RSV -associated \nmedically -attended LRTICritical RCT (1)Clesrovimab  is effective in preventing RSV -associated \nmedically -attended LRTIHigh\n2. RSV -associated LRTI \nwith hospitalization Critical RCT (1)Clesrovimab is effective in preventing RSV -associated LRTI \nwith hospitalizationHigh\n3. RSV -associated LRTI \nwith ICU admissionCritical RCT (1)Clesrovimab is effective in preventing RSV -associated LRTI \nwith ICU admissionModerate\n4. All -cause medically -\nattended LRTI Important RCT (1)Clesrovimab is not effective in preventing all cause medically -\nattended LRTIModerate\n5. All -cause LRTI with \nhospitalization Important RCT (1)Clesrovimab is moderately effective in preventing all -cause \nhospitalization with LRTIHigh\nHarms\n6. Serious adverse events​ \n(SAEs)Important RCT (1)SAEs were not more common in intervention group than \nplacebo groupModerate\nAbbreviations: LRTI = lower respiratory tract infection | RCT = randomized controlled trial80", "summary": "Evidence to Recommendations Framework :  Clesrovimab Danielle Moulia, MPH  Co-Lead, Maternal/Pediatric RSV Work Group   Advisory Committee on Immunization Practices April 16, 2025 1U.S. Centers for Disease Control and Prevention  Policy Question •Should clesrovimab  be recommended for all infants <8 months of age born  during or entering their first RSV season? 2 Evidence to Recommendations ( EtR) Framework EtR Domain Question(s) Public Health Problem ▪Is the problem of public health…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/02-Moulia-maternal-peds-RSV-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 80}
{"title": "03 Jones maternal peds RSV 508", "content": "Proposed clinical considerations for \nclesrovimab\nAdvisory Committee on Immunization Practices\nApril 16, 2025U.S. Centers for Disease Control and Prevention\nJefferson Jones MD MPH FAAP\nCo-Lead, Maternal/Pediatric RSV Work Group  \n•Similarities and differences in use of clesrovimab vs nirsevimab\n•Review of indications, timing, and dosing\n•Storage, handling, and administrationOutline\n2\nActive and Passive Immunity\nChapter 1: Principles of Vaccination | Pink Book | CDC•Antibodies produced by own immune \nsystem \n•After being exposed to a disease -causing \norganism, through\n−Infection\n−Vaccination\n•Protection takes time to develop but is \noften long -lasting  •Antibodies produced externally\n•Antibodies are transferred to a recipient\n−Maternal antibodies across the placenta to \nfetus\n−Transfusion of blood products \n−Receipt of antibody products\n•Provides immediate protection, but wanesPassive Immunity Active Immunity Acquired Immunity \n•Long -acting, monoclonal antibody manufactured by Merck\n•Passive immunization\n•Single -dose, manufacturer -filled syringe\n-105 mg/0.7 mL\n-Same dose for all infants regardless of weightInfant RSV Antibody –Clesrovimab\n \n•Clesrovimab  and nirsevimab  recommendations would be the same for use \nin infants younger than 8 months of age born during or entering their first \nRSV season \n-No preferential recommendation for use of clesrovimab  versus nirsevimab\n•Only  nirsevimab  recommended for children ages 8 through 19 months \nwho are at increased risk of severe RSV disease and entering their second \nRSV season \n-Infants eligible to receive nirsevimab  when entering second RSV season could \nhave received nirsevimab  or clesrovimab  for first RSV season\n-No effectiveness or safety concerns for using clesrovimab  for first RSV season and \nnirsevimab  for second RSV seasonProposed Use of Clesrovimab versus Nirsevimab\n5\n•One dose for infants younger than 8 \nmonths of age born during or \nentering their first RSV season \n(administration during October through \nMarch in most of the continental U.S.) if:\n-The mother did not receive RSV vaccine \nduring pregnancy\n-The mother’s RSV vaccination status is \nunknown\n-The infant was born less than 14 days after \nmaternal RSV vaccination\nUse of Nirsevimab for the Prevention of Respiratory Syncytial Virus Disease Among Infants and Young Children: \nRecommendations of the Advisory Committee on Immunization Practices — United States, 2023 | MMWR 6\n*Clesrovimab is not currently approved by FDA or recommended by ACIPProposed Recommendations for Use \nofRSV Antibody Immunizations\n(nirsevimab  or clesrovimab *) in Infants\n•Born to mothers who may not mount an adequate immune response to \nvaccination (e.g., immunocompromising conditions)\n•Born to mothers who have conditions associated with reduced \ntransplacental antibody transfer (e.g., living with HIV infection)\n•Infants who have procedures leading to loss of maternal antibodies (e.g., \ncardiopulmonary bypass, extracorporeal membrane oxygenation [ECMO], \nexchange transfusion) \n•Infants with substantially increased risk for severe RSV disease \n(e.g., hemodynamically significant congenital heart disease, ICU admission \nwith oxygen requirement at discharge) When RSV Antibody May Be Considered for \nInfants Born to Vaccinated Mothers\nRSV Immunization Guidance for Infants and Young Children | RSV | CDC  | ICU: intensive care unit\n\n•For infants born October through March\n-Administer in the first week of life —ideally during the birth hospitalization .\n-Infants with prolonged birth hospitalizations due to prematurity or other \ncauses should be immunized shortly before or promptly after discharge.\n-If not given in the hospital, administer in outpatient settings.\n•For infants born April through September\n-Optimal timing is shortly before the RSV season begins  \n(i.e., October through November)Timing of Infant RSV Antibody Administration\nUse of Nirsevimab  for the Prevention of Respiratory Syncytial Virus Disease Among Infants and Young Children: Recommendations of the Advisory C ommittee on Immunization Practices — United \nStates, 2023 | MMWR ; Beyfortus  Prescribing Information (fda.gov)\n\nOctober\n November\n December\n January\n February\n March\n April\n May\n June\n July\n August\n SeptemberInfant RSV Antibody Timing by Birth Month: \nFirst RSV Season in Most of Continental U.S.\nUse of Nirsevimab  for the Prevention of Respiratory Syncytial Virus Disease Among Infants and Young Children: Recommendations of the Advisory C ommittee on Immunization Practices — United \nStates, 2023 | MMWR , \n1 Most infants born to vaccinated mothers are not recommended to receive an RSV antibody\nInfants1 born April through September are \nrecommended to receive an RSV antibody shortly \nbefore the RSV season begins.Infants1 born October through March are \nrecommended to receive an RSV antibody within one \nweek of birth, ideally during birth hospitalization.\nRSV Seasonality Differs Based on Climate\nRSV Immunization Guidance for Infants and Young Children | RSV | CDC\nUse of Nirsevimab  for the Prevention of Respiratory Syncytial Virus Disease Among Infants and Young Children: Recommendations of the Advisory C ommittee on Immunization Practices — United \nStates, 2023 | MMWR\nIn jurisdictions with differing RSV seasonality (e.g., Alaska, southern Florida, \nPuerto Rico, and other jurisdictions with tropical climates), providers should \nfollow state, local, or territorial guidance on the timing of administration. \nSeasonal Administration Exceptions\nRSV Immunization Guidance for Infants and Young Children | RSV | CDC•Recommendations for the timing of \ninfant RSV antibody administration are \nflexible \n•Health care providers may use clinical \njudgment to determine when to give \ninfant RSV antibodies  outside of \nOctober through March.\n•Special circumstances to consider:\n-Travel to areas with increased RSV activity\n-Concern that patient may not return for a \nvisit when RSV antibodies should ideally \nbe administered\n\n•Recommended that CDC provide national recommendations with flexibility for state \nand local jurisdictions but avoid providing region -specific recommendations due to \nthe complexity of implementation\n•Supported current CDC recommendations on flexibility, but desired additional \nguidance on how to support decisionmakers for implementing flexibility\n•Making annual changes to the timing of RSV antibody administration would be \ncomplicated for jurisdictions and providers\n-Before 2020, the RSV season was fairly predictable with only minor year -to-year \nvariations. RSV seasonality appears to be returning to pre -pandemic patterns, but \nadditional years of data are needed to verify this\n-Since real -time RSV data trends can be difficult to interpret, state or local \njurisdictions may also choose to alter the timing of RSV antibody administration \nbased on local historical patterns of RSV seasonalityWork group considerations on RSV antibody \nadministration flexibility\n12\n•Not all RSV disease can be prevented, and for most of the Unites States, \nadministration of RSV antibody to newborns during October through March will \nprotect infants in their first few months of life during the peak of the RSV season\n•There is no evidence -based test positivity threshold above which RSV antibody is \nrecommended\n-3% is used to define the RSV season for surveillance purposes using the National \nRespiratory and Enteric Virus Surveillance System (NREVSS) PCR test positivity\n-3% is not a threshold to guide RSV antibody administration\n•Use of local RSV data may be the best source to guide action\n-Test positivity can differ by system based on testing practices and patient population\n-Other sources of data, including trends in RSV hospitalizations or the total numbers of \npositive tests can be consideredWork group considerations on RSV antibody \nadministration flexibility (2)\n13\n•Potential advantages\n-Can provide more time for infants to receive an RSV antibody prior to the start of \nthe RSV season \n-Potentially useful for jurisdictions with early seasonality\n•Potential disadvantages\n-Protection is expected to be greatest shortly after administration and decrease \nover time, but it is unknown how quickly protection decreases\n-Infants who receive an antibody in September could have reduced protection by \nthe peak of the season and towards the end of the seasonConsiderations for starting RSV antibody \nadministration prior to October\n14\n•Potential advantages\n-Infants born in April could be immunized shortly after birth, providing protection \nduring their first few months of life when they are highest risk for severe disease\n•Potential disadvantages\n-The risk of exposure and infection during the tail end of the RSV season might be \nlow\n-Most infants born to unvaccinated mothers are recommended to receive only \none dose of an RSV antibody\n-Most infants who receive a dose in April would not be recommended to receive a \ndose in October; a dose in October could provide protection for an entire RSV \nseasonConsiderations for extending RSV antibody \nadministration past March\n15\n•Because the timing of the onset, peak, and decline of RSV activity varies \ngeographically, public health authorities or regional medical centers may \nprovide additional guidance for infant RSV antibody administration for their \njurisdictions or patient populations\n•In areas with clear increases in RSV transmission prior to October, \nadministration prior to October can be considered\n•In areas with high RSV transmission through the end of March, \nadministering to newborns past March can be considered\n•In areas with historical data suggesting consistent RSV transmission \nbeginning prior to October or consistent high RSV transmission past the end \nof March, the standard months of seasonal administration can be modified \naccording to expected annual patternsConsiderations for administration of infant RSV \nantibody outside of October through March\n16\nChoose One Product to Prevent Severe RSV Disease in Infants\nMost infants will not need both maternal vaccination and an RSV antibody.\n*Proposed: clesrovimab  is not currently approved by FDA or recommended by ACIP\nMaternal RSV vaccination\n- Pfizer AbrysvoInfant RSV antibody\n-Nirsevimab\n-Clesrovimab*- or -\nMaternal \nRSV vaccine\nInfant RSV \nantibodyImmediate protection for baby after birth\nNo injection for the infant\nPotentially reduced protection in some situations (e.g., mother  is \nimmunocompromised or infant born soon after vaccination)\nPotential risk for hypertensive disorders of pregnancy\nDirect receipt of antibodies rather than relying on transplacental transfer \nProtection may wane more slowly than maternal RSV vaccine\nSide effects are usually mild and resolve quickly; hypersensitivity reactions are \nuncommon but have been reported\nDelayed administration could leave the infant unprotected1\n1 Infants born during October through March should be administered RSV antibody in the first week of life – ideally during the bir th hospitalization.  \nUse of the Pfizer Respiratory Syncytial Virus Vaccine During Pregnancy for the Prevention of Respiratory Syncytial Virus –Associa ted Lower Respiratory Tract Disease in Infants: Recommendations of the \nAdvisory Committee on Immunization Practices — United States, 2023 | MMWR ; Evaluation of Preterm Birth and SGA at Birth - October 2024 ACIP meeting\nConsiderations for Counseling Patients Regarding \nMaternal RSV Vaccine and Infant RSV Antibodies\n\nClesrovimab  (or Nirsevimab) and Palivizumab\n•If clesrovimab or nirsevimab is \ngiven to an infant or child… …then do not give palivizumab    \nduring the same RSV season.\nUse of Nirsevimab  for the Prevention of Respiratory Syncytial Virus Disease Among Infants and Young Children: Recommendations of the Advisory C ommittee on Immunization Practices — United \nStates, 2023 | MMWR , AAP Recommendations for the Prevention of RSV Disease in Infants and Children | Red Book Online | American Academy of Pediatr ics\nClesrovimab* \nor nirsevimabPalivizumab\n*Proposed: clesrovimab is not currently approved by FDA or recommended by ACIP\nInfant RSV Antibody Administration\nBeyfortus  Prescribing Information (fda.gov)•Route\n-Intramuscular injection\n•Site\n-Vastus lateralis muscle of anterolateral thigh\n-The gluteal muscle should not be used.\n•Coadministration\n-Simultaneous administration with vaccines is \nacceptable. \n\nExpected Clesrovimab Storage and Handling*\n*Not final as clesrovimab  has not yet been approved. It is expected that storage and handling of clesrovimab  will be similar the requirements of nirsevimab ; Nirsevimab  Package Insert (fda.gov)\nStore refrigerated between 2 °C and 8 °C (36°F and 46 °F).\nUse within 48 hours of removing from refrigerator.\n-May be kept at room temperature, between 20 °C and \n25°C (68°F and 77°F), for a maximum of 48 hours\nDo not freeze.\nProtect from light.Do not shake.\n\nAdminister the Correct RSV Immunization Product\nInfant RSV antibody \nonlyInfants and Some \nYoung Children\nAbrysvo  onlyDuring Pregnancy\n Older Adults\nDo not administer \nRSV antibody*, Arexvy, \nor mResvia  during \npregnancy.Do not administer \nAbrysvo, Arexvy, or \nmResvia to infants or \nchildren.Abrysvo  (Pfizer )\n Arexvy  (GSK)\n mResvia  (Moderna )\nDo not administer RSV \nantibody* to older adults.\n*Includes nirsevimab, clesrovimab, and palivizumab. Clesrovimab is not currently approved by FDA or recommended by ACIP\n•If RSV antibody is administered alone:\n-Report suspected adverse events (AEs) to MedWatch\n-www.fda.gov/medwatch\n•If RSV antibody is administered simultaneously with any \nvaccine:\n-Report suspected AEs to Vaccine Adverse Event Reporting System \n(VAERS)\n-vaers.hhs.gov\n-Additional reporting to MedWatch is not necessaryProposed Recommendation on How to Report \nAdverse Events After Infant RSV Antibody \nAdministration\nRSV Immunization Guidance for Infants and Young Children | RSV | CDC\n\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the \nauthors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention.", "summary": "Proposed clinical considerations for  clesrovimab Advisory Committee on Immunization Practices April 16, 2025U.S. Centers for Disease Control and Prevention Jefferson Jones MD MPH FAAP Co-Lead, Maternal/Pediatric RSV Work Group   •Similarities and differences in use of clesrovimab vs nirsevimab •Review of indications, timing, and dosing •Storage, handling, and administrationOutline 2 Active and Passive Immunity Chapter 1: Principles of Vaccination | Pink Book | CDC•Antibodies produced by own…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/03-Jones-maternal-peds-RSV-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 24}
{"title": "00 wharton talbot introduction 508", "content": "Centers for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation use. No rights  are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.Advisory Committee on Immunization Practices \n(ACIP)\nMEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES\nCenters for Disease Control and Prevention\n1600 Clifton Road, N.E.\nTom Harkin Global Communications Center, Kent “Oz” Nelson Auditorium\nAtlanta, Georgia 30329\n▪MUTE your lines at all times until you’re called on for discussion\n▪When the meeting is opened for discussion, please virtually  raise your hand\n▪During the discussion period, questions will be taken first from voting ACIP members \nand then from ex officio  members and liaison representatives.\n▪Please disable your video (a profile picture is fine, just no live video)Meeting Logistics\nPublic Comment\nThis meeting’s oral and written public comment processes designed to:\n✓Accommodate increased public \ninterest in ACIP’s work\n✓Maximize opportunities for comment\n✓Make public comment more \ntransparent and efficient\n✓Create a fair process for assigning \nlimited oral public comment time\nDocket ID CDC -2024 -0072\n▪Members of the ACIP agree to forgo participation in certain activities related to \nvaccines during their tenure on the committee. CDC has issued limited conflict of \ninterest waivers as follows:\n–Members who conduct vaccine clinical trials or serve on data safety monitoring \nboards are prohibited from participating in committee votes related to those \nvaccines. \n–Regarding other vaccines of the concerned company, a member may participate in \ndiscussions, with the provision that he/she abstains on all votes related to the \nvaccines of that company.  \n▪At the beginning of each meeting, ACIP members state any conflicts of interest.Disclosure of Conflicts of Interest\n▪Professor of pediatric infectious \ndisease and epidemiology at the \nUniversity of Colorado\n▪Expertise in global health and \ninfectious diseasesEdwin Jose Asturias, MD\n\n▪Gillings  Distinguished Professor \nin Public Health at the Gillings  \nSchool of Global Public Health at \nthe University of North Carolina \nat Chapel Hill\n▪Behavioral scientist who studies \nvaccination, tobacco cessation, \nand other health behaviorsNoel T. Brewer, PhD\n\n▪Associate Professor of Medicine \nat Harvard Medical School\n▪Director of the Travel Medicine \nCenter at Mount Auburn \nHospital \n▪Past President of the \nInternational Society of Travel \nMedicine, an organization with \nworldwide experts on vaccinesLin H. Chen, MD\n\n▪Infectious disease physician and \nProfessor of Medicine and \nEpidemiology at the University of \nWashington\n▪Studies respiratory viruses and \nvaccinesHelen Y . Chu, MD, MPH\n\n▪Chief Medical epidemiologist at \nMemorial Sloan Kettering Cancer \nCenter in New York City\n▪Infectious disease physician and \nProfessor of Medicine at Weill \nCornell Medical College at \nCornell UniversityMini Kamboj, MD\n\n▪Geriatrician and Professor of \nMedicine, Travelers Chair in \nGeriatrics and Gerontology\n▪Director of the UConn Center on \nAging at UConn HealthGeorge A. Kuchel , MD\n\n▪Consumer Representative\n▪Co-Director of the Vaccine \nEducation Center at Children’s \nHospital of PhiladelphiaCharlotte A. Moser, MS", "summary": "Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-23-24-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/00-wharton-talbot-introduction-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 12}
{"title": "01 Loehr Pneumococcal 508", "content": "Pneumococcal Vaccines\nOctober 2024, ACIP Meeting\nOctober 23, 2024\nPneumococcal Vaccines Work Group Chair\nJames Loehr, MD, FAAFPNational Center for Immunization and Respiratory Diseases\n1\nPneumococcal Vaccines Work Group\nACIP Members\nJamie Loehr                \nMini Kamboj\nGeorge Kuchel\nRobert Schechter  \nEx Officio Members\nLucia Lee                         \nTina Mongeau               \nUzo Chukwuma             \nMamodikoe Makhene \nMeenu Upadhyay        \nRisa Claytor                  \nLiaison Representatives\nLynn Fisher                     \nMonica Ardura              \nJason Goldman(Chair)\n(FDA)\n(FDA)\n(IHS)\n(NIH, primary)\n(NIH, alternate)\n(HRSA)\n(AAFP)\n(AAP/COID)\n(ACP , primary)Saba Hasan               \nDavid Nace                 \nCora Hoover\nJames McAuley        \nEva Wong                    \nRobert Hopkins         \nWilliam Schaffner     \nVirginia Caine            \nMary Hayney\nConsultants\nMonica Farley            \nKeith Klugman          \nKathy Poehling\nArthur Reingold\nLorry Rubin                 \nRichard Zimmerman(ACP , alternate)\n(AGS/ PALTmed )\n(AIM)\n(IDSA)\n(NACI)\n(NFID, primary)\n(NFID, alternate)\n(NMA)\n(APhA )\n(Emory)\n(Gates Foundation)\n(Wake Forest)\n(UC Berkeley)\n(CCMC)\n(U of Pittsburgh)\nCDC Contributors and Consultants\nCDC Lead\n•Miwako Kobayashi\nDivision of Bacterial Diseases\n•Emma Accorsi\n•Alison Albert\n•Adam L. Cohen\n•Ryan Gierke \n•Shelby Miller             \n•Noele Nelson\n•Wei Xing    \nArctic Investigations Program\n•Marc FischerImmunization Safety Office\n•Tarayn Fairlie\n•Julianne Gee\n•Pedro Moro  \n•John Su              \nImmunization Services Division\n•Sofia Bletnitsky\n•Andrew Leidner\n•Liz Velazquez\nGRADE/ EtR consultants\n•Doug Campos -Outcalt\n•Rebecca Morgan\nCurrently Recommended Adult Pneumococcal Vaccines\n1. U.S. FDA Approves CAPVAXIVE\n  (Pneumococcal 21 -valent Conjugate Vaccine) for Prevention of Invasive Pneumococcal Disease and Pneumococcal Pneumonia in Adults  - Merck.com1 3 4 5 6\nA6\nB7 \nF9\nV1\n41\n8\nC1\n9\nA1\n9\nF2\n3\nF2\n2\nF3\n3\nF8 1\n0\nA1\n1\nA1\n2\nF1\n5\nB2 9\nN1\n7\nF2\n01\n5\nA1\n5\nC1\n6\nF2\n3\nA2\n3\nB2\n4\nF3\n13\n5\nB\nPCV15\nPCV20\nPPSV23\nPCV21\n21-valent pneumococcal conjugate vaccine (CAPVAXIVETM, Merck):\n•Approved by the FDA for adults aged ≥18 years on June 17, 20241\nPCV15=15 -valent pneumococcal conjugate vaccine\nPCV20=20 -valent pneumococcal conjugate vaccine\nPCV21=21 -valent pneumococcal conjugate vaccine\nPPSV23=23 -valent pneumococcal polysaccharide vaccine\n1345366\n0102030405060708090100 Percent IPD\nPCV20/ non-PCV21 PCV20 and PCV21\nPCV21/ non-PCV20 NVT747388\n0102030405060708090100 Percent IPD\nPCV20/ non-PCV21 PCV20 and PCV21Proportion of IPD by vaccine -type among adults with a pneumococcal \nvaccine indication, 2018−2022\nPCV20/ non -PCV21 serotype:  1, 4, 5, 6B, 9V, 14, 18C, 19F, 23F, 15B\nPCV20/ in -PCV21 serotypes: 3, 6A, 7F, 19A, 22F, 33F, 8, 10A, 11A, 12F, +6C \nPCV21/ non-PCV20  serotypes: 9N, 17F ,20, 15A, 15C, 16F, 23A, 23B, 24F, 31, 35B PCV21:\n85%  coverage\n5PCV20:\n54%  coveragePCV21:\n81%  coverage\nPCV20:\n58%  coverage19-64 years old ( with a risk -based indication ) ≥65 years old\nGierke February 2024 ACIP meeting presentation \nNew Adult Pneumococcal Vaccines in Advanced Stages of Development\n1. Chichili  et al. Vaccine 2022; 2 .Vaxcyte  Completes Enrollment of Phase 2 Study Evaluating VAX -24 for the Prevention of Invasive Pneumococcal Disease (IPD) in Infants - Vaxcyte , Inc. ; 3. VAX-31 Phase ½ Study \nTopline Results in Adults Aged 50 and Older. September 3, 20241 3 4 5 6\nA6\nB7 \nF9\nV1\n41\n8\nC1\n9\nA1\n9\nF2\n3\nF2\n2\nF3\n3\nF8 1\n0\nA1\n1\nA1\n2\nF1\n5\nB2 9\nN1\n7\nF2\n01\n5\nA1\n5\nC1\n6\nF2\n3\nA2\n3\nB2\n4\nF3\n13\n5\nB7\nC\nPCV15\nPCV20\nPPSV23\nPCV21\nPn-\nMAPS24v\nVAX -24\nVAX -31\n24-valent pneumococcal vaccines:\n•Pn-MAPS24v (GSK): Completed phase 1/2 study for adults; Breakthrough Therapy Designation granted and \nnext steps in preparation; undergoing phase 2 studies in infants1\n•VAX-24 (Vaxcyte ): Completed enrollment for phase 2 studies in infants2; topline results anticipated in 2025\n31-valent pneumococcal vaccine (VAX -31, Vaxcyte ):\n•Reported topline results of phase 1/2 study in adults aged ≥50 years3; plan to initiate phase 3 pivotal non -\ninferiority study by mid-2025\n•Plans to initiate VAX -31 Infant Phase 2 Study in Q1 of 2025 following IND submission and clearance \nAdults currently recommended to receive a dose of \npneumococcal conjugate vaccine (PCV)\n•Adults aged ≥65 years who have not received a PCV1\n•Adults aged 19 –64 years with certain underlying conditions or risk \nfactors2 who have not received a PCV1\n•Certain adults who have received PCV13 but have not received \nPCV203 \n1. Excludes PCV7\n2. Alcoholism; chronic heart, liver, or lung disease; chronic renal failure; cigarette smoking; cochlear implant; congenital or acquired asplenia; CSF leak; diabetes mellitus; generalized \nmalignancy; HIV infection; Hodgkin disease; immunodeficiency; iatrogenic immunosuppression; leukemia, lymphoma, or multiple m yeloma; nephrotic syndrome; solid organ \ntransplant; or sickle cell disease or other hemoglobinopathies\n3. Adults who have not completed the recommended vaccine series, or shared clinical decision -making for adults aged ≥65 years who h ave completed the recommended vaccine \nseries\nPneumococcal Vaccine for Adults Aged ≥19 Years: Recommendations of the Advisory Committee on Immunization Practices, United S tates, \n2023 | MMWR (cdc.gov) 7\nPCV21 is unique from other PCVs in that it was \ndeveloped to target adult disease\n•PCV21 was developed to target pneumococcal serotypes that commonly \ncause disease in adults.\n•The manufacturer currently does not have plans to seek an indication for \nroutine PCV21 use in infants. \n•The manufacturer will seek an indication for use of PCV21 in children aged \n2–18 years with a risk condition for which there is a phase 3 trial currently \nin progress.*\n-PCV7 and PCV13 provided indirect protection against vaccine serotypes when \nused in children.\n-We do not expect PCV21 to offer similar indirect protection from its additional \nserotypes.\n*NCT06177912 8\nSummary of Work Group (WG) discussion presented \nat the June 2024 ACIP meeting \n•The WG agreed that available evidence supports PCV21 use for adults \ncurrently recommended to receive a PCV.\n•The WG could not reach a consensus on whether the age -based \nrecommendation for PCV21 should be lowered from ≥65 years to ≥50 \nyears. \n•The majority of WG members believed there was insufficient evidence \npresented to support lowering the age -based recommendation for other \nrecommended PCVs (i.e., PCV15, PCV20). \n9\nRequests from the Committee to the WG at the June \nACIP meeting\n•Present summary of data on whether age -based recommendation for \npneumococcal vaccines should be lowered to age ≥50 years for all PCVs \n(not just PCV21) at the October ACIP meeting\n-Voting members felt that there were not enough data to make a decision on PCVs \nother than PCV21\n-Anticipating implementation challenges by having different age -based \nrecommendations by vaccine\n•Request to also consider discontinuing the recommendation for PPSV23 \n10\nPICO for WG discussion through October 2024\nCMC=chronic medical conditions (i.e., alcoholism; chronic heart disease, including congestive heart failure and cardiomyopath ies; chronic liver disease; chronic lung disease, including \nchronic obstructive pulmonary disease, emphysema, and asthma; cigarette smoking; or diabetes mellitus); IC=immunocompromising  condition(i.e., chronic renal failure, nephrotic \nsyndrome, immunodeficiency, iatrogenic immunosuppression, generalized malignancy, HIV infection, Hodgkin disease, leukemia, l ymp homa, multiple myeloma, solid organ transplant, \ncongenital or acquired asplenia, or sickle cell disease or other hemoglobinopathies). Those with a cerebrospinal fluid leak a nd a cochlear implant are also included among those with a \nrisk-based vaccine indication.Policy question: Should a single dose of pneumococcal conjugate vaccine (PCV) be recommended \nfor all PCV -naïve adults aged 50 –64 years? \nPopulation PCV-naïve adults aged 50 –64 years in the United States\nIntervention One dose of PCV15*, PCV20, or PCV21\n*In series with PPSV23\nComparison Current risk -based vaccine recommendation (CMC or IC)\nOutcomes Vaccine type (VT) -invasive pneumococcal disease, VT -non-bacteremic  pneumococcal \npneumonia, VT -pneumococcal mortality, serious adverse events\nInitial Policy Options Considered by the WG\n1. Lower the age -based recommendation for all PCVs to age ≥50 years\n2. Lower the age -based recommendation for all PCVs to age ≥60 years or \nage ≥55 years\n3. Lower the age -based recommendation to age ≥50 years for PCV21 only\n4. Shared clinical decision -making for PCV use for adults aged 50 –64 years \nwho currently do not have a risk -based vaccine indication\n5. Status quo (i.e., age -based at age ≥65 years, risk -based for younger \nadults)\n12\nPrimary Options Considered by the WG\n1. Lower the age -based recommendation for all PCVs to age ≥50 years\nLower the age -based recommendation for all PCVs to age ≥60 years (or age \n≥55 years) \n3. Lower the age -based recommendation to age ≥50 years for PCV21 only\nShared clinical decision -making for PCV use for adults aged 50 –64 years who \ncurrently do not have a risk -based vaccine indication\n5. Status quo  (i.e., age -based at age ≥65 years, risk -based for younger \nadults)\n13\nFinal recommendation of the WG\n1. Lower the age -based recommendation for all PCVs to age ≥50 years\n- Majority supported this option after targeted discussion of the policy question\n- Future booster dose may be needed to avoid increased pneumococcal disease \nburden in older adults \n- Key uncertainties remain:\n• Indirect effects from new pediatric pneumococcal vaccines\n• Duration of protection from adult vaccination\n• Impact of new higher -valency vaccines for adults\nLower the age -based recommendation for all PCVs to age ≥60 years (or age \n≥55 years) \n14\nKey factors in the WG recommendations\n1. Health equity: Higher pneumococcal disease rates in Black/African American adults, \nwith earlier peak\n2. Risk prevalence: 33 –54% of adults aged 50 –64 years already with indication for risk -\nbased pneumococcal vaccination*\n3. Vaccine coverage: Age -based recommendation likely to improve uptake vs. risk -\nbased recommendation\n4. Simplicity: Easier to implement uniform recommendation across all PCVs\n5. Economic consideration: PCV21 at age 50 (and 65 years)  had lower cost/QALY \ngained than  PCV20 , while both PCV21 and PCV20 improved health outcomes\n6. Serotype coverage: the serotype compositions of PCV20 and PCV21 are quite \ndifferent\n*Data is for adults with any of the following condition and is not an exhaustive list of conditions: chronic heart disease, c hronic lung disease, chronic liver disease, diabetes, smoking, \nalcoholism, weakened immune system due to prescriptions, weakened immune system due to health condition, solid cancer (not in cluding non -melanoma skin cancer or unknown type \nof skin cancer) and blood cancer. Source NHIS 2020.\n†Except for In certain adult populations in the western United States where high percentages (i.e., ≥30%) of IPD caused by se rotype 4 have occurred15\nToday’s Session\n16Introduction Dr. Jamie Loehr (ACIP , WG Chair)\nEconomic Analysis and public health impact \nof PCV use for adults aged ≥50 yearsDr. Charles Stoecker (Tulane)\nSummary of economic analyses of PCV use \nin adults aged ≥50 yearsDr. Andrew Leidner \n(CDC/NCIRD)\nSummary of WG Interpretation of EtR and \npolicy options on PCV use in adults aged \n≥50 yearsDr. Miwako Kobayashi \n(CDC/NCIRD)\nClinical considerations for PCV use in adultsDr. Miwako Kobayashi \n(CDC/NCIRD)", "summary": "Pneumococcal Vaccines October 2024, ACIP Meeting October 23, 2024 Pneumococcal Vaccines Work Group Chair James Loehr, MD, FAAFPNational Center for Immunization and Respiratory Diseases 1 Pneumococcal Vaccines Work Group ACIP Members Jamie Loehr                 Mini Kamboj George Kuchel Robert Schechter   Ex Officio Members Lucia Lee                          Tina Mongeau                Uzo Chukwuma              Mamodikoe Makhene  Meenu Upadhyay         Risa Claytor                   Liaison…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-23-24-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/01-Loehr-Pneumococcal-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 16}
{"title": "02 Stoecker Pneumococcal 508", "content": "1Economic Analysis and Public Health Impact of PCV \nuse for Adults Aged ≥50 Years\nCharles Stoecker\nTulane University\nCelia Scott Weatherhead School of Public Health and Tropical \nMedicine\nACIP\nOctober 23, 2024\n\n2Conflicts of Interest\n❑Dr. Stoecker has no conflicts of interest to declare.\n3Acronyms\n❑ PCV: pneumococcal conjugate vaccine\n❑ PCV20: 20 valent PCV\n❑ PCV21: 21 valent PCV\n❑ VE: vaccine effectiveness\n❑ VT: vaccine type\n❑ ST: serotype\n❑ NBP: non -bacteremic pneumonia\n❑ IPD: invasive pneumococcal disease\n❑ IPT: inpatient\n❑ OPT: outpatient\n❑ QALY: quality adjusted life year\n❑ IC: immunocompromised\n❑ CMC: chronic medical conditions, but not IC\n❑ NIS: National Immunization Survey\n❑ ABCs: Active Bacterial Core Surveillance System\n4Methods:  Study Question\n❑Evaluate cost effectiveness of an age -based \nrecommendation for PCV20 or PCV21 in adults younger \nthan age 65\n▪Motivation is to get higher coverage among risk -based adults\n•Additionally get coverage among general population\n❑Evaluate\n▪Program cost/savings\n▪Changes in disease, medical costs, nonmedical costs, and work \nproductivity costs\n•Limited societal perspective\n▪Population\n•Cohort of 4,051,078 50 -year -olds\n•Separate model buckets for:\noImmunocompromised (IC) –HIV, Cancer, Organ Transplants, \nDialysis\noChronic medical conditions (CMC) –Diabetes, Heart Disease, Lung \nDisease, Liver Disease, Alcoholism\noOthers –”General”\n5Two Modeling Strategies\n❑Moving Strategies\n▪Moving age -based recommendation from 65 to age 50\n▪Shifts disease burden from younger to older adults\n▪Moving strategy will overcount benefits\n•Overstates savings from not vaccinating at age 65 years\n•Overstates unprotected time if waning is longer than 15 years\n•If the future policy considerations will add a later age -based vaccination \nafter reevaluation in the future\noReevaluations could be motivated by waning evaluation or higher \nvalency vaccinations\n❑Adding Strategies\n▪Adding vaccination at 50 in addition to 65\n▪In the future, clinicians may prefer to administer a booster dose at age \n65 years in the \"moving strategy\" to ensure protection for older adults\n▪Maintains protective benefits for older adults from current age -based \nrecommendation\n6Specific Strategies to Evaluate\n❑Moving Strategies\n❑Adding Strategies\n❑Repeat with PCV21Intervention Comparator\nPCV20 at age 50 PCV20 at CMC/IC & PCV20 at age 65\nPCV20 at age 60 PCV20 at CMC/IC & PCV20 at age 65\nIntervention Comparator\nPCV20 at ages 50 & 65 PCV20 at CMC/IC & PCV20 at age 65\nPCV20 at ages 60 & 75 PCV20 at CMC/IC & PCV20 at age 65\n7Conceptual Model\nNBP\nBackground mortality from non -pneumococcus related illness is included in all branches, but not displayed in the model for brevi ty.\nAbbreviations: IPT -inpatient case, OPT -outpatient case, IPD -invasive pneumococcal disease, NBP -non -bacteremic  pneumoniaIPT Case\nIPT Case\nOPT Case\n8Model Inputs\n❑IPD rates, all -cause IPT and OPT NBP rates, IPD cases resulting in \nfatality were estimated by age - and risk group (general/CMC/IC). \n❑Age -group specific IPT NBP case fatality rates were applied to the 3  \nrisk groups\n❑Vaccine effectiveness (VE) was estimated by risk group and \noutcome (IPD/NBP)\n▪VE against serotype 3 was lower than other VT\n▪Vaccine serotype effectiveness was the same across PCV20 and PCV21\n❑Vaccine coverage was estimated separately by age group (50 –64, \n65+) and for existing risk -based recommendations (age 50 -64)\n▪Updated from June 2024 presentation with more granular data\nSee supplemental slides for the specific estimates used in the model.  Additional details are also available in the earlier v ersion \nof the model that was presented at ACIP in June 2024 (Stoecker 2024 \"Economic Assessment of PCV21 in US Adults\")\n9Vaccine Price\n❑PCV20 $288.66a\n❑PCV21 $319.43b\n❑Administration 50 -64 years: $30.49c\n❑Administration 65+ years:  $21.07d\n❑Travel + patient time cost: $44.46e\na Payment Allowance Limits for Medicare Part B for PCV20.\nb Applied ratio of PCV21 to PCV20 price from manufacturer model and applied to PCV20 Medicare price. Sensitivity analysis uses upper bound of manufacturer \nPCV21 price range.\nc Tsai et al. AJPM 2019. Updated to 2023 dollars.\nd Average Medicare maximum allowable reimbursement for immunization administration (HCPCS code 90471) across all Medicare Admin istrative Contractors, \n2023.\ne Travel cost from Maciosek  et al. Am J Prev Med 2006. Updated to 2023 dollars.\n10Waning Immunity Assumptions\n❑No decline in effectiveness for first five years a\n❑Wane to zero over next 10 or 15 years b\naPatterson  S, Webber C, Patton M, Drews  W, Huijts  SM, Bolkenbaas  M, et al. A post hoc assessment of duration of protection in CAPiTA  (Community \nAcquired Pneumonia immunization Trial in Adults). Trials in Vaccinology. 2016;5.:92 -96.\nb van Werkhoven  CH, Huijts  SM, Bolkenbaas  M, Grobbee  DE, Bonten  MJ. The Impact of Age on the Efficacy of 13 -valent Pneumococcal Conjugate \nVaccine in Elderly. Clin Infect Dis 2015;61(12):1835 -8.00.10.20.30.40.50.60.70.80.91\n01234567891011121314151617181920% Initial Effectiveness\nYears Since Initial Vaccination\nWane by 15 Wane by 20\n11Herd Effects from PCV20 in Children\n❑Apply serotype group -specific declines observed in \nPCV13 types (+6C, -3, -19F) in adults after PCV13 \nintroduction in children\n❑Apply to additional types in PCV20 but not in PCV13\n❑Run versions of the model with and without these herd \neffects to assess importance\nYear Remaining Proportion of Disease\n1 0.755161\n2 0.496227\n3 0.339094\n4 0.244074\n5 0.187125\n6 0.156599\n7+ No further declines\nSource: Kobayashi et al. Poster presented at: 13th Meeting of the International Society of Pneumonia & Pneumococcal Diseases,  March 2024\n12Moving Strategies\n1315 Y ear Waning, With Herd Effects\nPCV20 PCV20 PCV21 PCV21\n50 vs. 65 60 vs. 65 50 vs. 65 60 vs. 65\nIPD Cases 44 32 458 464\nHospitalized Pneumonia Cases 871 808 1,925 1,977\nNon -hospitalized Pneumonia Cases\n722 590 1,498 2,017\nDeaths due to IPD 12 9 69 66\nDeaths due to Hospitalized Pneumonia 37 35 83 83\nQALYs 66 -102 -210 -671\nTotal Cost (million$) -$76 -$206 -$121 -$218\n$ Saved / QALY Lost Cost -Saving 2,023,745 575,614 324,164\nUndiscounted Cases 50 -64 -4,031 -3,217 -9,338 -6,265\nUndiscounted Cases 65+ 9,681 6,374 22,261 14,735\nUndiscounted Deaths 50 -64 -69 -54 -154 -106\nUndiscounted Deaths 65+ 203 136 530 356\nNote: Undiscounted cases include invasive pneumococcal disease cases as well as non -bacteremic  pneumonia cases (both inpatient and outpatient).\n14Adding Strategies\n1515 Y ear Waning, With Herd Effects\nPCV21 at Age \n50 and 65PCV21 at Age \n60 and 75PCV20 at Age \n50 and 65PCV20 at Age \n60 and 75\nIPD Cases -932 -941 -434 -354\nHospitalized Pneumonia Cases -1,367 -4,117 -600 -1,868\nNon -hospitalized Pneumonia Cases -6,000 -7,233 -2,635 -3,467\nDeaths due to IPD -100 -133 -46 -46\nDeaths due to Hospitalized Pneumonia -38 -171 -17 -77\nQALYs 2,070 1,581 956 741\nLife-years\n2,633 2,407 1,214 1,092\nCosts (million $)\nTotal Cost $444 $189 $523 $270\nMedical Costs -$141 -$177 -$64 -$82\nVaccine Costs $689 $403 $635 $372\nWork Loss -$103 -$37 -$48 -$20\nCost Ratios ($)\nCost/QALY 214,430 119,665 546,811 364,497\nCost/Life -year 168,533 78,612 430,913 247,411\nNote: All strategies are compared to current recommendations; risk -based use between ages 50 -64 and age -based use at age 65.\n1620 Y ear Waning, With Herd Effects\nPCV21 at Age \n50 and 65PCV21 at Age \n60 and 75PCV20 at Age \n50 and 65PCV20 at Age \n60 and 75\nIPD Cases -989 -949 -449 -355\nHospitalized Pneumonia Cases -1,455 -3,595 -618 -1,649\nNon -hospitalized Pneumonia Cases -6,386 -7,075 -2,710 -3,389\nDeaths due to IPD -106 -153 -48 -51\nDeaths due to Hospitalized Pneumonia -40 -155 -17 -70\nQALYs 2,144 1,445 967 676\nLife-years\n2,747 2,199 1,234 992\nCosts (million $)\nTotal Cost $433 $206 $521 $278\nMedical Costs -$150 -$162 -$66 -$75\nVaccine Costs $689 $403 $635 $372\nWork Loss -$105 -$35 -$48 -$19\nCost Ratios ($)\nCost/QALY 202,019 142,373 539,097 411,202\nCost/Life -year 157,728 93,531 422,657 280,039\n1715 Y ear Waning, No Herd Effects\nPCV21 at Age \n50 and 65PCV21 at Age \n60 and 75PCV20 at Age \n50 and 65PCV20 at Age \n60 and 75\nIPD Cases -1,283 -1,275 -795 -704\nHospitalized Pneumonia Cases -1,781 -6,587 -1,115 -5,139\nNon -hospitalized Pneumonia Cases -7,819 -10,216 -4,892 -7,346\nDeaths due to IPD -137 -184 -84 -100\nDeaths due to Hospitalized Pneumonia -49 -281 -31 -223\nQALYs 2,778 2,177 1,725 1,480\nLife-years\n3,541 3,390 2,193 2,310\nCosts (million $)\nTotal Cost $364 $109 $433 $170\nMedical Costs -$189 -$253 -$118 -$178\nVaccine Costs $689 $403 $635 $372\nWork Loss -$136 -$41 -$84 -$25\nCost Ratios ($)\nCost/QALY 131,028 50,122 251,037 114,909\nCost/Life -year 102,804 32,186 197,417 73,619\n18Limitations\n❑Uncertainty around waning & herd effects\n❑Sequelae from IPD not modeled explicitly\n❑Uncertainties about the pneumococcal disease trends due to \npneumococcal serotypes that are no longer included in PCV21 \n(e.g., serotype 4, 19F)\n❑Disruption from changing pneumococcal schedule not modeled\n19Moving Strategy Summary\n❑Moving age -based vaccination from age 65 to lower ages:\n▪All scenarios result in increased net cases\n•Lowers cases and deaths in ages 50 -64\n•Increases cases and deaths in ages 65+\n▪Lower cost\n▪Also true under longer vaccine waning scenarios and scenarios without herd \nimmunity from childhood program (Appendix)\n20Adding Strategy Summary\n❑Adding a second age -based vaccination results in increased QAL Ys \nand costs  compared with the current recommendation\n▪ICERs range from $50k/QALY to $500k/QALY\n▪ICERs are always lower for PCV21 recommendations than PCV20 recommendations\n❑Assuming no herd effects improves economic  efficiency of both \nPCV20 & PCV21\n▪Change in $/QALY is greater in PCV20 than PCV21\n▪But this change is not large enough to make PCV20 more efficient than PCV21\n❑Assumptions surrounding vaccine waning are minimally impactful \non ICERs\n▪Waning is extended  in both the intervention and comparison strategies \n❑Vaccination at later ages is more economically efficient\n▪Vaccination at 60 & 75 is lower $/QALY than vaccination at 50 & 65 (or 55 & 70)\n21Thank you!\nPlease send comments to:\ncfstoecker@tulane.edu\nContributors:\nAndrew Leidner\nMiwako Kobayashi\nBo-Hyun Cho\nYin Wang\nCheryl Ward\nNational Center for Immunization & Respiratory Diseases\nHSREB – Econ Team\n\n22Serotype Group18-49\nYears50-64\nYears65-74\nYears75-84\nYears85+\nYears\n% PCV20 only -4-19F\n   (1, 5, 6B, 9V, 14, 18C, 23F, 15B, including \nisolates reported as 15BC)1.99% 1.52% 3.09% 1.01% 1.08%\n% PCV20 & PCV21 -3\n(6A, 7F, 19A, 22F, 33F, 8, 10A, 11A, 12F) +6C 34.44% 41.95% 32.72% 32.32% 33.33%\n% PCV21 only -35B\n   (9N, 17F, 20, 15A, 15C, 16F, 23A, 23B, 24F, 31)30.13% 30.70% 31.48% 29.29% 35.48%\n% serotype 3 13.91% 12.46% 17.28% 21.21% 14.25%\n% serotype 4 4.97% 2.43% 1.23% 0.00% 0.00%\n% serotype 19F 4.97% 4.56% 3.70% 3.03% 3.01%\n% serotype 35B 2.65% 0.91% 4.32% 5.05% 3.23%\nRatio PCV21 only:PCV20 only serotypes 2.75 3.71 4.46 8.50 9.46\nSource: Active Bacterial Core Surveillance 2018 -2019. For multivariate sensitivity analyses distributions are beta -pert with -/+20% for low and high.IPD Serotype Distributions, General\n23Serotype Group18-49\nYears50-64\nYears65-74\nYears75-84\nYears85+\nYears\n% PCV20 only -4-19F\n   (1, 5, 6B, 9V, 14, 18C, 23F, 15B, including \nisolates reported as 15BC)0.49% 0.71% 1.88% 2.17% 1.81%\n% PCV20 & PCV21 -3\n(6A, 7F, 19A, 22F, 33F, 8, 10A, 11A, 12F) +6C 36.99% 33.62% 30.36% 32.79% 28.62%\n% PCV21 only -35B\n   (9N, 17F, 20, 15A, 15C, 16F, 23A, 23B, 24F, 31)30.33% 32.67% 30.83% 32.52% 33.70%\n% serotype 3 11.34% 17.96% 21.91% 17.07% 17.39%\n% serotype 4 9.99% 4.35% 1.25% 0.27% 0.72%\n% serotype 19F 3.08% 2.45% 2.66% 2.44% 2.17%\n% serotype 35B 2.59% 3.01% 4.23% 5.15% 6.88%\nRatio PCV21 only:PCV20 only serotypes 2.43 4.75 6.06 7.72 8.63IPD Serotype Distributions, CMC\nSource: Active Bacterial Core Surveillance 2018 -2019. For multivariate sensitivity analyses distributions are beta -pert with -/+20% for low and high.\n24IPD Serotype Distributions, IC\nSerotype Group18-49\nYears50-64\nYears65-74\nYears75-84\nYears85+\nYears\n% PCV20 only -4-19F\n   (1, 5, 6B, 9V, 14, 18C, 23F, 15B, including \nisolates reported as 15BC)6.02% 3.92% 3.30% 2.88% 0.00%\n% PCV20 & PCV21 -3\n(6A, 7F, 19A, 22F, 33F, 8, 10A, 11A, 12F) +6C 28.92% 31.63% 30.03% 37.50% 48.31%\n% PCV21 only -35B\n   (9N, 17F, 20, 15A, 15C, 16F, 23A, 23B, 24F, 31)31.33% 33.73% 33.99% 26.44% 25.84%\n% serotype 3 15.66% 8.43% 11.55% 10.10% 4.49%\n% serotype 4 1.20% 1.20% 1.32% 0.00% 0.00%\n% serotype 19F 3.61% 3.61% 3.30% 1.44% 5.62%\n% serotype 35B 6.02% 6.63% 8.91% 9.62% 5.62%\nRatio PCV21 only:PCV20 only serotypes 3.45 4.62 5.42 8.35 5.60\nSource: Active Bacterial Core Surveillance 2018 -2019. For multivariate sensitivity analyses distributions are beta -pert with -/+20% for low and high.\n25NBP Serotype Distributions\nSerotype Group18-49\nYears50-64\nYears65+\nYears\n% PCV20 only -4-19F\n   (1, 5, 6B, 9V, 14, 18C, 23F, 15B)0.6% 0.7% 1.1%\n% PCV20 & PCV21 -3\n(6A, 7F, 19A, 22F, 33F, 8, 10A, 11A, 12F) +6C 3.0% 4.5% 3.9%\n% PCV21 only -35B\n   (9N, 17F, 20, 15A, 15C, 16F, 23A, 23B, 24F, 31)3.2% 4.2% 2.4%\n% serotype 3 1.1% 2.0% 1.4%\n% serotype 4 0.0% 0.2% 0.2%\n% serotype 19F 0.1% 0.9% 0.7%\n% serotype 35B 0.8% 0.6% 0.7%\nRatio PCV21 only:PCV20 only serotypes 5.7 2.7 1.6\nSource: Merck adjusted SSUAD serotype distribution data. \nNote that the serotype distribution is among all community -acquired pneumonia, not limited to pneumococcal pneumonia.\n For multivariate sensitivity analyses distributions are beta -pert with -/+20% for low and high.\n26IPD Rates per 100k\nSource: Active Bacterial Core Surveillance System, 2017 -2018; NHIS 2017 –2018. For multivariate sensitivity analyses distributio ns are beta -pert with -/+20% for \nlow and high. Risk Group19-49\nYears50-64\nYears65-74\nYears75-84\nYears85+\nYears\nGeneral 2.09 6.09 8.25 13.90 33.06\nCMC 8.09 24.04 25.89 33.34 58.57\nIC 16.22 37.28 35.10 36.81 46.38\n27NBP Hospitalization Rates per 100k\nSource: MarketScan  & Optum databases. 2013 -2015 data. (Pelton et al. CID 2019) (95% CIs in parenthesis)Risk \nGroup19-49\nYears50-64\nYears65-74\nYears75+\nYears\nGeneral 35 (35, 36) 88 (87, 90) 191 (185, 197) 957 (938, 975)\nCMC 207 (202, 212) 429 (423, 425) 941 (925, 957) 2745 (2717, 2774)\nIC 701 (681, 721) 1226 (1207, 1244) 2124 (2087, 2162) 3992 (3944, 4040)\n28NBP Outpatient  Rates per 100k\nSource: Tong et al. 2014 data. BMC Health Serv Res 2018. For multivariate sensitivity analyses distributions are beta -pert with -/+20% f or low and high.Risk Group19-49\nYears50-64\nYears65-74\nYears75-84\nYears85+\nYears\nGeneral 322.92 385.04 491.98 1366.22 2378.97\nCMC 1872.91 1886.72 2410.70 3962.03 6899.00\nIC 6361.40 5352.10 5461.00 5738.10 9991.70\n29IPD Cases Resulting in Fatality\nSource: Active Bacterial Core Surveillance System, 2017 -2018. For multivariate sensitivity analyses distributions are beta -pert with -/+20% for low and high.Risk Group19-49\nYears50-64\nYears65-74\nYears75-84\nYears85+\nYears\nGeneral 5.54% 8.73% 7.93% 11.25% 17.30%\nCMC 7.24% 11.06% 12.22% 12.82% 22.97%\nIC 10.04% 14.27% 13.97% 11.33% 17.62%\n30IPT NBP Cases Resulting in Fatality\nBase Low High\n18-49 Years 1.6 0.4 2.9\n50-64 Years 2.8 1.1 4.4\n65-74 Years 3.5 1.5 5.5\n75-84 Years 4.1 2.2 6.0\n85+ Years 5.3 3.3 7.2\nSource: NIS2018 (lower bound: ICD -10 code J13 or J181 for primary diagnosis; upper bound: ICD -10 code J13 or J181 in ANY locatio n; base: mean of LB and UB). \nLow and High parameters used in beta -pert distribution \n31Vaccine Effectiveness\na. Bonten  NEJM 2015 (per protocol)\nb. Point estimate from Pilishvili et al. ISPPD2018 abstract, lower bound set to 0, upper bound from Lewis 2020 ISPPD poster\nc. Suaya  Vaccine 2018; 1477 -1483. \nd. Applied the ratio of IPD VE/Pneumonia VE for all PCV13 types to the point estimate for ST3 IPD VE.  General CMC IC\nPCV vs VT ( -ST3) IPDa 75.0 (41.4, 90.8) 75.0 (41.4, 90.8) 25.0 (13.8, 30.3)\nPCV vs ST3 IPDb 26.0 (0, 53.4) 26.0 (0, 53.4) 8.7 (0, 17.8)\nPCV vs VT ( -ST3) NBPc 66.7 (11.8, 89.3) 40.3 (11.4, 60.2) 15.0 (4.7, 21.8)\nPCV vs ST3 NBPd 15.6 (0, 32.0) 15.6 (0, 32.0) 5.2 (0, 10.7)\n32Coverage Rates\nJune 2024\nInputs Updated\nPCV Age -based 50 -64 39.65b 47.6e\nPCV Age -based 65+ 56c 70f\nRisk -based (50 -64) 22.2a 37.5f\na. NHIS 2021 data https://www.cdc.gov/vaccines/imz -managers/coverage/adultvaxview/pubs -resources/vaccination -coverage -adults -2021.html ;\nb. Mean of  NHIS 2021 for Zoster Vaccine in adults 60 -64 years; and estimate for PCV15/PCV20 coverage in adults 65 years and older \nc. Mean of NHIS 2021 any pneumococcal coverage; and any PCV13 coverage data in Medicare beneficiaries aged ≥65 years, 2019\ne.     Applied the ratio of vaccine coverage among ages 50 -64/65+ for Influenza and COVID -19 vaccines to age -based pneumococcal vaccine coverage in \nadults aged 65+years\nf.       BRFSS 2022, any pneumococcal vaccine coverage\n33Utility Decrements\nVariable QAL Y DecrementsaImplied Healthy Days \nLostb\nIPD0.0709 \n(0.0509, 0.0909)25.9\nIPT NBP0.0709 \n(0.0509, 0.0909)25.9\nOPT NBP0.0045 \n(0.00399, 0.00501)1.6\na QALY values from Mangen  et al. 2015 Eur Respir J (95% CIs in parenthesis)\nb Health days lost were include on this slide to illustrate in relatable terms the magnitude of health loss associated with QAL Y decrements. Healthy days lost \ncalculated by multiplying QALY decrement by 365. \nc Alternate values are inverse variance weighted values from Tang et al. 2021 J Pub Health. Source material places higher decre ment on outpatient disease \nthan inpatient disease for age 65+.Pneumococcal Disease \nTreatment Intensity, AgeQALY \nDecrement\nOutpatient, 19 -64 0.0094\nInpatient, 19 -64 0.0396\nOutpatient, 65+ 0.0586\nInpatient, 65+ 0.0087Alternate Utility Decrementsc\n34Baseline QAL Y Values\nAge General CMC/IC\n50-55 0.83 (0.78,0.88) 0.72 (0.67,0.77)\n56-60 0.81 (0.76,0.86) 0.69 (0.64,0.74)\n61-65 0.77 (0.72,0.82) 0.63 (0.58,0.68)\n66-70 0.76 (0.71,0.81) 0.57 (0.52,0.62)\n71-75 0.74 (0.69,0.79) 0.54 (0.49,0.59)\n76-80 0.7 (0.65,0.75) 0.52 (0.47,0.57)\n81-85 0.63 (0.58,0.68) 0.51 (0.46,0.56)\n86+ 0.51 (0.46,0.56) 0.51 (0.46,0.56)\nSisk, 2003.\n35Disease Cost (2023$)\nData for ages 19 -64 from MarketScan  2019 -2022. Data for 65+ from CMS Medicare claims 2019 -2022.  95% CI from bootstrapping mean values with 1,000 \niterations. All costs converted to 2023$ using CPI Medical Care before bootstrapping. See appendix slide for ICD -10 codes.Disease Setting Cost 95% CI\n19-64 YearsIPD IPT $64,018.10 $61,559.31 $66,424.61\nNBP IPT $58,423.99 $55,923.53 $60,908.13\nNBP OPT $362.38 $339.44 $385.24\n65+ YearsIPD IPT $27,564.22 $27,039.18 $28,149.20\nNBP IPT $21,300.64 $20,825.64 $21,800.98\nNBP OPT $318.22 $308.06 $328.70\n36ICD -10 Codes for Medical Cost Extraction\nDisease ICD-10 Codes\nIPD A40.3, A40.9+B95.3, A41.9+B95.3, R78.81+B95.3, G00.1, G00.2+B95.3, \nG00.9+B95.3, G03.9+B95.3, J86.x+B95.3, J85.1+B95.3, A40.3 + at least one code \nfrom \"All -cause\", A40.9+B95.3 + at least one code from \"All -cause\", \nA41.9+B95.3 + at least one code from \"All -cause\", R78.81+B95.3 + at least one \ncode from \"All -cause\", A40.9 & J13, A41.9 & J13, R78.81 & J13, M00.1x, \nK65.8+B95.3, I30.1+B95.3, I33.0+B95.3, I33.9 +B95.3, K65.2+B95.3, \nM86.1x/M86.2x/M86.9+B95.3, M00.0x, M00.2x, M00.8x, M00.9 + B95.3\nNBP J13, J15.9+B95.3, J18.0/J18.1+B95.3, J18.8/J18.9+B95.3\nAll-cause (for \nsatisfying some \ndefinitions of \nIPD)J12.x (J12.0, J12.1, J12.2, J12.3, J12.81, J12.89, J12.9), J13, J18.1, A48.1, J14, J15.0, \nJ15.1, J15.2x (J15.20, J15.211, J15.212, J15.29), J15.3, J15.4, J15.5, J15.6, J15.8, \nJ15.9, J15.7, J16.x (J16.0, J16.8), A22.1, A37.X1, B25.0, B44.0, J17, J18.0, J18.2, \nJ18.8, J18.9, J09.X1, J10.0x (J10.00, J10.01, J10.08), J11.0x (J11.00, J11.08)\n37Work Loss\nAgeLabor Force \nParticipation \nRate (%)aMedian Daily \nWage ($)b\n19 to 24 71 99.71\n25 to 34 83.2 148.86\n35 to 44 83 175.57\n45 to 54 81.1 176.14\n55 to 64 65.2 169.43\n65 to 74 26.6 157.29\n75+ 8.2 157.29\na US Bureau of Labor Statistics. \nb Current Population Survey, 2023.\nc Altawalbeh  SM, Wateska  AR, Nowalk  MP, Lin CJ, Harrison LH, Schaffner W, Zimmerman RK, Smith KJ. Societal cost of racial pneumococcal disease disparities in \nUS adults aged 50 years or older. Applied Health Economics and Health Policy. 2024 Jan;22(1):61 -71.\nd Used ratio of days of work loss from outpatient (14) to inpatient pneumonia (18) allowed by Marine Corps policy and applied t o inpatient durations of illness \nfrom Altawalbeh  2024. Vold  Pepper P, Owens DK. Cost -effectiveness of the pneumococcal vaccine in the United States Navy and Marine Corps. Clinical \ninfectious diseases. 2000 Jan 1;30(1):157 -64.Base High Low\nInpatientc 34 17 51\nOutpatientd 26.4 13.2 39.7Labor Force Participation and Daily Wage Duration of Work Loss\n3815 Y ear Waning, With Herd Effects (Moving)\nPCV20 PCV20 PCV20 PCV21 PCV21 PCV21\n50 vs. 65 55 vs. 65 60 vs. 65 50 vs. 65 55 vs. 65 60 vs. 65\nIPD Cases 44 34 32 458 459 464\nHospitalized Pneumonia Cases 871 897 808 1,925 2,032 1,977\nNon -hospitalized Pneumonia Cases\n722 647 590 1,498 1,529 2,017\nDeaths due to IPD 12 10 9 69 69 66\nDeaths due to Pneumonia 37 39 35 83 88 83\nQALYs 66 -9 -102 -210 -419 -671\nTotal Cost (million$) -$76 -$133 -$206 -$121 -$171 -$218\n$ Saved / QALY Lost Cost -Saving 14,014,611 2,023,745 575,614 407,176 324,164\nUndiscounted Cases 50 -64 -4,031 -4,269 -3,217 -9,338 -9,579 -6,265\nUndiscounted Cases 65+ 9,681 8,757 6,374 22,261 20,177 14,735\nUndiscounted Deaths 50 -64 -69 -72 -54 -154 -160 -106\nUndiscounted Deaths 65+ 203 184 136 530 482 356\n3920 Y ear Waning, With Herd Effects (Moving)\nPCV20 PCV20 PCV20 PCV21 PCV21 PCV21\n50 vs. 65 55 vs. 65 60 vs. 65 50 vs. 65 55 vs. 65 60 vs. 65\nIPD Cases 71 59 65 560 559 571\nHospitalized Pneumonia Cases 1,269 1,299 1,129 2,742 2,890 2,655\nNon -hospitalized Pneumonia Cases\n1,193 1,131 1,042 2,283 2,479 2,915\nDeaths due to IPD 16 14 13 84 83 80\nDeaths due to Pneumonia 54 56 48 118 124 111\nQALYs -20 -96 -184 -376 -606 -848\nTotal Cost (million$) -$67 -$121 -$194 -$106 -$145 -$194\n$ Saved / QALY Lost 3,325,061 1,252,046 1,056,802 283,008 239,889 228,155\nUndiscounted Cases 50 -64 -4,263 -4,095 -2,999 -10,237 -9,311 -5,866\nUndiscounted Cases 65+ 12,226 10,605 7,643 27,976 24,322 17,557\nUndiscounted Deaths 50 -64 -73 -70 -51 -168 -155 -99\nUndiscounted Deaths 65+ 261 228 165 678 594 432\n4015 Y ear Waning, No Herd Effects (Moving)\nPCV20 PCV20 PCV20 PCV21 PCV21 PCV21\n50 vs. 65 55 vs. 65 60 vs. 65 50 vs. 65 55 vs. 65 60 vs. 65\nIPD Cases 418 438 482 796 825 881\nHospitalized Pneumonia Cases 3,598 3,747 3,432 3,941 4,134 3,928\nNon -hospitalized Pneumonia Cases\n5,861 5,917 5,638 5,226 5,327 5,730\nDeaths due to IPD 63 64 66 116 118 120\nDeaths due to Pneumonia 141 148 135 160 169 158\nQALYs -830 -1,038 -1,185 -876 -1,203 -1,537\nTotal Cost (million$) -$40 -$86 -$136 -$101 -$141 -$165\n$ Saved / QALY Lost 48,348 82,895 114,542 114,808 116,909 107,388\nUndiscounted Cases 50 -64 -7,694 -8,032 -4,831 -12,353 -12,711 -7,613\nUndiscounted Cases 65+ 30,465 27,551 20,002 38,099 34,498 25,117\nUndiscounted Deaths 50 -64 -130 -134 -80 -211 -217 -131\nUndiscounted Deaths 65+ 586 534 396 847 771 571\n4120 Y ear Waning, No Herd Effects (Moving)\nPCV20 PCV20 PCV20 PCV21 PCV21 PCV21\n50 vs. 65 55 vs. 65 60 vs. 65 50 vs. 65 55 vs. 65 60 vs. 65\nIPD Cases 489 514 567 938 974 1,038\nHospitalized Pneumonia Cases 4,845 4,991 4,408 5,391 5,625 5,100\nNon -hospitalized Pneumonia Cases\n7,221 7,246 6,845 6,659 6,921 7,202\nDeaths due to IPD 74 75 77 137 139 140\nDeaths due to Pneumonia 194 201 176 222 232 207\nQALYs -1,059 -1,280 -1,402 -1,143 -1,508 -1,819\nTotal Cost (million$) -$18 -$54 -$107 -$77 -$100 -$128\n$ Saved / QALY Lost 16,782 42,282 76,328 67,272 66,407 70,122\nUndiscounted Cases 50 -64 -8,627 -7,815 -4,503 -13,830 -12,398 -7,117\nUndiscounted Cases 65+ 38,671 33,563 24,125 48,108 41,795 30,100\nUndiscounted Deaths 50 -64 -146 -131 -75 -236 -212 -122\nUndiscounted Deaths 65+ 770 677 493 1,096 962 700\n4215 Y ear Waning, With Herd Effects (Adding)\nPCV21 at Age \n50 and 65PCV21 at Age \n55 and 70PCV21 at Age \n60 and 75PCV20 at Age \n50 and 65PCV20 at Age \n55 and 70PCV20 at Age \n60 and 75\nIPD Cases -932 -930 -941 -434 -402 -354\nHospitalized Pneumonia Cases -1,367 -2,584 -4,117 -600 -1,141 -1,868\nNon -hospitalized Pneumonia Cases -6,000 -6,699 -7,233 -2,635 -2,990 -3,467\nDeaths due to IPD -100 -104 -133 -46 -44 -46\nDeaths due to Pneumonia -38 -93 -171 -17 -41 -77\nQALYs 2,070 1,768 1,581 956 829 741\nLife-years\n2,633 2,420 2,407 1,214 1,116 1,092\nCosts (million $)\nTotal Cost $444 $330 $189 $523 $416 $270\nMedical Costs -$141 -$171 -$177 -$64 -$77 -$82\nVaccine Costs $689 $570 $403 $635 $526 $372\nWork Loss -$103 -$69 -$37 -$48 -$33 -$20\nCost Ratios ($)\nCost/QALY 214,430 186,838 119,665 546,811 501,851 364,497\nCost/Life -year 168,533 136,496 78,612 430,913 372,691 247,411\n4320 Y ear Waning, With Herd Effects (Adding)\nPCV21 at Age \n50 and 65PCV21 at Age \n55 and 70PCV21 at Age \n60 and 75PCV20 at Age \n50 and 65PCV20 at Age \n55 and 70PCV20 at Age \n60 and 75\nIPD Cases -989 -995 -949 -449 -419 -355\nHospitalized Pneumonia Cases -1,455 -2,522 -3,595 -618 -1,115 -1,649\nNon -hospitalized Pneumonia Cases -6,386 -6,966 -7,075 -2,710 -3,083 -3,389\nDeaths due to IPD -106 -123 -153 -48 -49 -51\nDeaths due to Pneumonia -40 -93 -155 -17 -41 -70\nQALYs 2,144 1,798 1,445 967 827 676\nLife-years\n2,747 2,480 2,199 1,234 1,120 992\nCosts (million $)\nTotal Cost $433 $333 $206 $521 $418 $278\nMedical Costs -$150 -$169 -$162 -$66 -$75 -$75\nVaccine Costs $689 $570 $403 $635 $526 $372\nWork Loss -$105 -$69 -$35 -$48 -$33 -$19\nCost Ratios ($)\nCost/QALY 202,019 184,959 142,373 539,097 505,534 411,202\nCost/Life -year 157,728 134,122 93,531 422,657 373,616 280,039\n4415 Y ear Waning, No Herd Effects (Adding)\nPCV21 at Age \n50 and 65PCV21 at Age \n55 and 70PCV21 at Age \n60 and 75PCV20 at Age \n50 and 65PCV20 at Age \n55 and 70PCV20 at Age \n60 and 75\nIPD Cases -1,283 -1,284 -1,275 -795 -765 -704\nHospitalized Pneumonia Cases -1,781 -3,846 -6,587 -1,115 -2,776 -5,139\nNon -hospitalized Pneumonia Cases -7,819 -8,896 -10,216 -4,892 -5,715 -7,346\nDeaths due to IPD -137 -145 -184 -84 -85 -100\nDeaths due to Pneumonia -49 -143 -281 -31 -106 -223\nQALYs 2,778 2,357 2,177 1,725 1,490 1,480\nLife-years\n3,541 3,285 3,390 2,193 2,096 2,310\nCosts (million $)\nTotal Cost $364 $247 $109 $433 $318 $170\nMedical Costs -$189 -$237 -$253 -$118 -$155 -$178\nVaccine Costs $689 $570 $403 $635 $526 $372\nWork Loss -$136 -$86 -$41 -$84 -$52 -$25\nCost Ratios ($)\nCost/QALY 131,028 104,656 50,122 251,037 213,705 114,909\nCost/Life -year 102,804 75,085 32,186 197,417 151,924 73,619\n4520 Y ear Waning, No Herd Effects (Adding)\nPCV21 at Age \n50 and 65PCV21 at Age \n55 and 70PCV21 at Age \n60 and 75PCV20 at Age \n50 and 65PCV20 at Age \n55 and 70PCV20 at Age \n60 and 75\nIPD Cases -1,389 -1,382 -1,278 -860 -818 -699\nHospitalized Pneumonia Cases -1,931 -3,780 -5,748 -1,209 -2,749 -4,499\nNon -hospitalized Pneumonia Cases -8,476 -9,491 -10,120 -5,305 -6,258 -7,363\nDeaths due to IPD -148 -173 -212 -91 -100 -113\nDeaths due to Pneumonia -53 -145 -256 -33 -109 -204\nQALYs 2,928 2,422 1,958 1,817 1,526 1,305\nLife-years\n3,761 3,394 3,046 2,328 2,150 2,028\nCosts (million $)\nTotal Cost $344 $247 $133 $421 $319 $188\nMedical Costs -$205 -$235 -$230 -$127 -$154 -$161\nVaccine Costs $689 $570 $403 $635 $526 $372\nWork Loss -$140 -$87 -$39 -$87 -$53 -$23\nCost Ratios ($)\nCost/QALY 117,514 102,083 68,174 231,438 208,701 144,205\nCost/Life -year 91,491 72,848 43,822 180,616 148,188 92,771", "summary": "1Economic Analysis and Public Health Impact of PCV  use for Adults Aged ≥50 Years Charles Stoecker Tulane University Celia Scott Weatherhead School of Public Health and Tropical  Medicine ACIP October 23, 2024  2Conflicts of Interest ❑Dr. Stoecker has no conflicts of interest to declare. 3Acronyms ❑ PCV: pneumococcal conjugate vaccine ❑ PCV20: 20 valent PCV ❑ PCV21: 21 valent PCV ❑ VE: vaccine effectiveness ❑ VT: vaccine type ❑ ST: serotype ❑ NBP: non -bacteremic pneumonia ❑ IPD: invasive…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-23-24-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/02-Stoecker-Pneumococcal-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 45}
{"title": "03 Leidner Pneumococcal 508", "content": "Summary of three economic analyses on the use of \nPCVs among 50-64 year old  adults in the United States\nAndrew J. Leidner, Sofia Bletnitsky\nApplied Research, Implementation Science and Evaluation (ARISE) Branch\nImmunization Services Division (ISD)\nNCIRD\nACIP Meeting\nOctober 23, 2024NCIRD/ISD/ARISE\nDisclaimer: Views and opinions expressed in this presentation are the authors and do not necessarily represent the views and opinions of the \nCenters for Disease Control and Prevention .1\n•This presentation summarizes work conducted by three modeling teams\n-Tulane -CDC team\n•Charles Stoecker (Tulane University), Yin Wang (Tulane University), Miwako Kobayashi (CDC), Andrew \nLeidner (CDC), Bo -Hyun Cho (CDC), Cheryl Ward (CDC)\n-Merck team\n•Kwame Owusu -Edusei , Zinan  Yi , Muloongo  Simuzingili , Elamin  Elbasha , Elmira Flem , Thomas Weiss, \nHeather Platt, Kristen Feemster, Kelly Johnson, Ulrike Bushwald , Craig Roberts, Don Yin\n-Pfizer team\n•Ahuva  Averin , Jeffrey Vietri, Mark Atwood, Dhwani Hariharan, Mark Rozenbaum, Alejandro Cane, Paul \nBalmer, Jelena Vojicic , Paula Peyrani , Ray FarkouhAcknowledgements\n2Disclaimer: Views and opinions expressed in this presentation are the authors and do not necessarily represent the views and opinions of the \nCenters for Disease Control and Prevention. \n•Andrew Leidner, Sofia Bletnitsky: None\n•Tulane -CDC team: None\n•Merck team:\n-Merck manufactures the PCV21, PCV15 and PPSV23 vaccines\n•Pfizer team:\n-Pfizer manufactures the PCV20 and PCV13 vaccinesConflicts of interest statement\n3\nTerminology\n4Abbreviation Full term/Meaning\nCER Cost -effectiveness ratio\nCFR Case -fatality rate\nCMC Chronic medical conditions but not immunocompromised  \nCR Current recommendations ( Risk-based use of PCV at ages 50 -64 and age -based use of PCV at age 65 )\nIC Immunocompromising conditions\nICER Incremental cost -effectiveness ratio\nIPD Invasive pneumococcal disease\nNBP Non -bacteremic  pneumonia\nPCV15 15-valent pneumococcal conjugate vaccine\nPCV20 20-valent pneumococcal conjugate vaccine\nPCV21 21-valent pneumococcal conjugate vaccine\nQALYs Quality -adjusted life years\nSA Sensitivity analyses\n•Background on cost -effectiveness analysis\n•Model overview\n•Main results\n•Sensitivity analyses\n•Discussion of other models\n•Limitations\n•SummaryOutline\n5\n•Cost -effectiveness analyses compare the costs and outcomes of two or more strategies by \nestimating an incremental cost -effectiveness ratio (ICER)\n-An ICER is an estimated cost per unit of health outcome gained\n•Outcomes: averted cases, averted hospitalizations, quality -adjusted life years (QALYs)\n•Cost per QALY gained  ($/QALY)\n-ICERs always compare 2 potential strategies\n•Strategies are referred to as the “intervention” and “comparator”\n•E.g., vaccination vs. no vaccination, vaccine schedule A vs. vaccine schedule B, new \nvaccination vs. status quoWhat is cost -effectiveness analysis (CEA)?\n6CostsPCV@50 -64 – CostsCR         Change in costs\n   =                         = $/Outcome\nOutcomesPCV@50 -64 – OutcomesCR                Change in outcomes\nICER= Incremental cost -effectiveness ratio; CR= Current recommendations\nWhat is cost -effectiveness analysis (CEA)?\n7  CostsPCV@50 -64 – CostsCR              Change in costs\n                          =                            = \n$/Outcome\n OutcomesPCV@50 -64 – OutcomesCR     Change in outcomes\nEconomic model inputs\n  Vaccine characteristics\n     Efficacy\n     Safety\n     Cost per dose\n          …\n  Disease burden inputs\n     Incidence rates\n     Health care costs\n     Mortality rates\n          …Economic model estimated  outputs\n   Costs\n      Vaccination program costs\n      Disease -related costs\n   Health outcomes\n      Prevented episodes of disease\n      QALYs gainedEconomic \nmodel\nCR= Current recommendations\nInterpreting an incremental cost -effectiveness ratio \n(ICER)  Change in costs\n                          = $/Outcome\n  Change in outcomes\nDominatedHigher costs & \nhigher health\nLower costs & \nlower healthCost -savingBetter health outcomes\n(Change in outcomes > 0)Worse health outcomes\n(Change in outcomes < 0)Higher costs\n(Change in costs > 0)\nLower costs\n(Change in costs < 0)\nCR\n8CR= Current recommendations\nInterpreting an incremental cost -effectiveness ratio \n(ICER)  Change in costs\n                          = $/Outcome\n  Change in outcomes\nDominatedHigher costs & \nhigher health\nLower costs & \nlower healthCost -savingBetter health outcomes\n(Change in outcomes > 0)Worse health outcomes\n(Change in outcomes < 0)Higher costs\n(Change in costs > 0)\nLower costs\n(Change in costs < 0)\nCR\n9 CR= Current recommendations$1,000,000\n                            = $125,000/QALY\n    8 QALYs\n$500,000\n                              = $62,500/QALY\n    8 QALYs\nEstimate BEstimate A\n•Should a single dose of pneumococcal conjugate vaccine (PCV) be \nrecommended for all PCV -naïve adults aged 50 –64 years?Policy question\n10\n•Comparator (current recommendations): Risk-based vaccination with PCV at ages \n50-64 years and age -based vaccination with PCV at age 65 yearsa\n•Intervention (younger age -based vaccination): Age-based vaccination with PCV at \nage 50 years“Moving” comparisons in the models\nAlternate comparisons\n11CMC = chronic medical conditions; IC = immunocompromised; PCV =  pneumococcal conjugate vaccine.\na.In the main results, all three models include some form of vaccination at age 65, but the coverage rates at age 65 varied across  models and vary within specific scenarios. Some scenarios presented later did not include age -based \nvaccination at 65.\nb.This table shows coverage assumptions from the Tulane -CDC model. The other models have different vaccination coverage rate assumptio ns, and the coverage rate assumptions can vary across different scenarios within each of the \nmodels. Age group Risk groupPCV coverage by strategybModeled impact \nof policy change Comparator Intervention\n50-64CMC/IC 38% 48%PCV use \nincreases by 10%\nGeneral 0% 48%PCV use \nincreases by 48%\n65+ General and CMC/IC 70% 0%PCV use \ndecreases by 70%\n•Comparator (current recommendations): Risk-based vaccination with PCV at ages \n50-64 years and age -based vaccination with PCV at age 65 yearsa\n•Intervention (younger age -based vaccination): Age-based vaccination with PCV at \nage 50 years and age 65 yearsa“Adding” comparisons in the models\nMain comparisons\n12CMC = chronic medical conditions; IC = immunocompromised; PCV =  pneumococcal conjugate vaccine.\na.In the main results, all three models include some form of vaccination at age 65, but the coverage rates at age 65 varied across  models and vary within specific scenarios. Some scenarios presented later did not include age -based \nvaccination at 65.\nb.This table shows coverage assumptions from the Tulane -CDC model. The other models have different vaccination coverage rate assumptio ns, and the coverage rate assumptions can vary across different scenarios within each of the \nmodels. Age group Risk groupPCV coverage by strategybModeled impact \nof policy change Comparator Intervention\n50-64CMC/IC 38% 48%PCV use \nincreases by 10%\nGeneral 0% 48%PCV use \nincreases by 48%\n65+ General and CMC/IC 70% 70%No change \nin PCV use\n•Comparator (current recommendations): Risk-based vaccination with PCV at ages \n50-64 years and age -based vaccination with PCV at age 65 yearsa\n•Intervention (younger age -based vaccination): Age-based vaccination with PCV at \nage 50 years and age 65 yearsa\n-These comparisons can more directly estimate the impacts of expanding coverage among \n50-64 year olds\n-Older adult groups (i.e., 65+) would receive some protection from disease during a time \nin life with high incidence, disease severity, and costs due to pneumococcal disease\n•Some vaccine -naïve individuals may not receive a PCV until age 65, even with an age -\nbased recommendation at age 50+\n•Vaccine duration of protection assumed to last 10 -20 years; there is limited available data \non duration of protection after 5 years\n•In the future, new vaccines may be available for adults who have received PCV“Adding” comparisons in the models\nMain comparisons\n13a. In the main results, all three models include some form of vaccination at age 65, but the coverage rates at age 65 varied acr oss models and vary within specific scenarios. Some scenarios presented later did not include age -based \nvaccination at 65.\nModel overview\n14Model characteristics Tulane -CDC Merck Pfizer\nCohort type Single cohortMulti -cohort \n(Single -cohort in SA)Multi -cohort \n(Single -cohort in SA)\nAnalytic model time frame Lifetime Lifetime Lifetime \nBase case perspective Limited societalaSocietalSocietal\n(Healthcare in SA)\nCurrency year 2023 $ US 2023 $ US 2023 $ US\nVaccine cost per doseb PCV20: $289\nPCV21: $319PCV20: $261\nPCV21: $287PCV20: $262\nOther vaccine -associated costs per \ndoseAdmin: $30 (50 -64); $21 (65+) \nTravel: $44Admin: $31 (50 -64); $25 (65+)\nTravel: $45Admin: $31\nVaccine coverage change in the \nintervention among 50 -64 year oldsGeneral: +48%\nCMC/IC: +10%General: +39%\nCMC/IC: 0% (+8% in SA )General: +21%\nCMC/IC: +15 to 17% \n(+20 to +32% in SA)\nSerotype coverage ratio: \nPCV21:PCV20c3.7 to 9.5 \n(vaccine -unique types)4.3 to 6.3\n(vaccine -unique types)NA\nSA=sensitivity analyses; CMC/IC= chronic medical conditions/immunocompromised. \na. The limited societal perspective does not include non -market production as part of productivity losses.\nb. Private sector list prices were $262 for PCV20  and $288 for PCV21 on October 1, 2024. The Tulane -CDC model cost per dose inclu des an additional cost of reimbursement from health system payers, which is typically higher than \nthe list price.\nc. This is the ratio of PCV21 -only type IPD disease to PCV20 -only type IPD disease among 50+ year olds, the ranges come from diffe rent age stratifications used in the models.\nModel overview, cont.\n15Model characteristics Tulane -CDC Merck Pfizer\nYears until PCV protection wanes to 0%15 yearsa \n(20 years in SA)15 yearsa \n(20 years, varied waning \nrates in SA)16 yearsa\nVE vs IPD in year 15, general population 0% (30% in SA) 0% (75% in SA) 36%\nVE vs NBP based on all -cause pneumonia in alternative \nVE approachNo No Yes\nInclude indirect effectsb Yes \n(None in SA)Yes\n(Higher and none in SA)Yes\n(Reduced in SA)\nIndirect effects magnitude (PCV20 non -PCV13 types), \nwhen included81% reduction \nby year 533% reduction by year 4 \n(64% by year 5 in SA)70% reduction \nby year 5\nInclude long -term post -IPD sequalae (e.g., disability) No Yes No\nInclude age -adjusted and risk -stratified incidence Yes Yes Yes\nProductivity loss for disease -related deaths at age 60c$331,732 $684,301 $330,654 to $333,623\nSA=sensitivity analyses; VE= vaccine effectiveness; IPD= invasive pneumococcal disease; NBP= non -bacteremic  pneumonia; \na.The duration of protection assumptions were similar in the base case of Tulane -CDC and Merck, constant VE for the first 5 years fol lowed by a linear decline to VE=0 at year 15. The Pfizer model assumed a slower decline in VE from \nyears 5 to 15, resulting in about 30% more vaccine protection than the Tulane -CDC and Merck models.\nb. In these models, indirect effects refer to the reduced pneumococcal disease among adults from the use of PCVs in pediatric po pulations.\nc. Productivity losses for a death at age 60 for each model were calculated by the economics review team. These include lost pro ductivity due to a premature death at age 60, assuming average life expectancy of 80 years, with total \nlosses discounted to present values.\nMain results\nCost -effectiveness estimates ($/QALY)\n16Intervention ComparatorICER ($/QALY)\nTulane -CDCa Merck Pfizerd\nAge-based vaccination \nat 50 and 65 with PCV21Current recommendations\nwith PCV21131,023 to \n214,430251,048 to \n425,455b NA\nAge-based vaccination \nat 50 and 65 with PCV20Current recommendations \nwith PCV20251,037 to \n546,811548,114 to \n879,117c56,376* to \n133,524\nCurrent recommendations= Age-based vaccination at 65 and risk -based vaccination at 50 -64; ICER= incremental cost -effectiveness ratio; QALY= quality -adjus ted life year.\na.Ranges  are from different assumptions about indirect effects from PCV20 use in children. The lower value assumes no indirect effects , the higher value assumes base case inputs for indirect effects.\nb.The results are single -cohort estimates and the range is from scenarios that use different assumptions about vaccination coverage a nd indirect effects. The lower value assumes no indirect effects and CMC/IC individuals aged 50 \nexperience an increase in vaccination coverage due to the age -based recommendation at age 50; higher value assumes higher indire ct effects and that CMC/IC individuals are not affected by the age -based recommendation at age 50. \nc.The results are single -cohort estimates and the range is from scenarios that include different population groups. The lower values do not include indirect effects, the higher values have higher indirect effects. These scenarios did not \ninclude increase vaccination coverage among CMC/IC individuals aged 50 -64.\nd.The range in the Pfizer estimates is from scenarios that use different assumptions about vaccine effectiveness and indirect effec ts. The lower value is based on vaccine effectiveness estimates from studies with all -cause pneumonia \nas the primary outcome and assumes higher indirect effects from PCV15 -non-PCV13 type disease; the higher value is based on estim ates that rely on quantifying the amount of circulating vaccine -type disease with base case indirect \neffect assumptions.\n* The Pfizer model did not include vaccination at age 65+ in either the intervention or the comparator for this scenario.•Tulane -CDC model ICERs for PCV20 and PCV21 were lower than Merck, higher than Pfizer\n•In the models that assessed both PCV20 and PCV21, PCV21 use had lower ICERs\nScenario results: Higher VE and duration of protection\nCost -effectiveness estimates ($/QALY)\n17Intervention ComparatorICER ($/QALY)\nTulane -CDCa Merckb Pfizerc\nAge-based vaccination \nat 50 and 65 with PCV21Current recommendations \nwith PCV21117,514 to \n202,019146,089 NA\nAge-based vaccination \nat 50 and 65 with PCV20Current recommendations \nwith PCV20231,438 to \n422,657342,26362,264 to \n99,632\nCurrent recommendations= Age-based vaccination at 65 and risk -based vaccination at 50 -64. ICER= incremental cost -effectiveness ratio; QALY= quality -adjus ted life year.\na.In this scenario in the Tulane -CDC model, the duration of protection waned to 0% at year 20. The ranges are from different assumpt ions about indirect effects from PCV20 use in children. The lower value assumes no indirect effects, \nthe higher value assumes base case inputs for indirect effects.\nb.In this scenario in the Merck model, the duration of protection scenario assumed initial VE was constant (no waning) for 20 year s and declined to 0% VE at year 21. The results in this table are from single -cohort estimates. \nc.In this scenario in the Pfizer model, the VE against NBP was set to the high value in the input range, VE against IPD and durati on of protection remained at base case levels.•Scenarios with higher VE and longer duration of protection (longer than 15 years) had lower \nICERs\nScenario results: Reduced or no indirect effectsa\nCost -effectiveness estimates ($/QALY)\n18Intervention ComparatorICER ($/QALY)\nTulane -CDC Merck Pfizerb\nAge-based vaccination \nat 50 and 65 with PCV21Current recommendations \nwith PCV21131,028251,048 to \n306,396cNA\nAge-based vaccination \nat 50 and 65 with PCV20Current recommendations\nwith PCV20251,037 548,11456,376 to \n93,127*\nCurrent recommendations= Age-based vaccination at 65 and risk -based vaccination at 50 -64. ICER= incremental cost -effectiveness ratio; QALY= quality -adjus ted life year.\na. In these models, indirect effects refer to the reduced pneumococcal disease among adults from the use of PCV20 in pediatric p opulations.\nb. The range in the Pfizer estimates is from scenarios that use different assumptions about vaccine effectiveness. The lower val ue is based on vaccine effectiveness estimates from studies with all -cause pneumonia as the primary \noutcome, the higher value is based on estimates that rely on quantifying the amount of circulating vaccine -type disease. \nc.These  results are single -cohort estimates and the range is from scenarios that use different assumptions about vaccination coverage. The lower value assumes CMC/IC individuals aged 50 experience an increase in vaccination \ncoverage due to the age -based recommendation at age 50, the higher value assumes CMC/IC individuals are not affected by the age -based recommendation at age 50. \n* The Pfizer model did not include vaccination at age 65+ in either the intervention or the comparator for these scenarios.•Scenarios with reduced or lower indirect effects from pediatric PCV20 use yielded lower \nICERs, particularly for PCV20 strategies\n•Merck health equity model\n-The Merck model team submitted a separate report that estimated the impact of 50 -64 \nyear old PCV use on health equity\n-This report used the Atkinson indexa to quantify the inequality with and without 50 -64 \nyear old PCV vaccination\n-Health inequality was found to be reduced with a lower age -based recommendation\n•Pittsburgh modelb\n-Summarized in the June 2024 ACIP meetingc\n-Estimated health equity benefits were associated with 50 -64 year old PCV vaccination\n-Estimated lower ICERs than the other models presented todayDiscussion, other models\n19a. Yang et al. 2020. Impact of Socioeconomic Differences on Distributional Cost -effectiveness Analysis . Atkinson 1970.  On the measurement of inequality .\nb. Altawalbeh  et al. 2024. Cost-effectiveness of an in -development adult -formulated 21 -valent pneumococcal conjugate vaccine in US adults aged 50 years or older .\nc. Leidner et al. 2024. Summary of three economic analyses on the use of 21 -valent pneumococcal conjugate vaccine (PCV21) among adults in the United Sta tes.\n•Substantial uncertainty and limited data available for several key model inputs\n-Vaccine effectiveness and duration of protection\n-Indirect effects from pediatric PCV20 use\n-Vaccination coverage impacts in a younger age -based recommendation policy\n•Additional uncertainties about several model assumptions \n-Future epidemiology of pneumococcal serotypes that are not included in PCV21 (e.g., serotype 4, 19F)\n-Impact of supplemental doses with PCVs and new higher -valency vaccines\n•Impacts on vaccination implementation due to changing the pneumococcal vaccine schedule \nwere not includedLimitations\n20\nSummary of model findings ($/QALY)\n21•From the “adding” comparisons, all strategies improved health, but none were cost -saving\n•Cost per QALY gained estimates for PCV20 had a wider range, more uncertainty than PCV21\n•In two of three models, PCV21 had lower costs per QALY gained than PCV20\nCurrent recommendations= Age-based vaccination at 65 and risk -based vaccination at 50 -64; QALY= quality adjusted life year.0 100,000 200,000 300,000 400,000 500,000 600,000 700,000 800,000 900,000 1,000,000\nIncermental cost -effectiveness ratio (ICER) ($/QALY)Cost -effectiveness estimates for PCV21 and PCV20 vaccination \nat age 50 and 65 years vs. current recommendations\nPCV21\nPCV21PCV20\nPCV20\nPCV20Tulane -CDC \nmodel\nMerck \nmodel\nPfizer \nmodel\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position \nof the Centers for Disease Control and Prevention.\nThank you for your attention and thank you to those that contributed to this presentation\n22Tulane -CDC team\nCharles Stoecker (Tulane University)\nYin Wang (Tulane University) \nMiwako Kobayashi (CDC) \nAndrew Leidner (CDC)\nBo-Hyun Cho (CDC)\nCheryl Ward (CDC)Merck team\nKwame Owusu -Edusei\nZinan  Yi\nElamin  Elbasha\nElmira Flem\nThomas Weiss\nHeather Platt\nKristen Feemster\nKelly Johnson\nUlrike Bushwald\nCraig Roberts\nDon YinPfizer team\nAhuva  Averin\nJeffrey Vietri\nMark Atwood\nDhwani Hariharan\nMark Rozenbaum\nAlejandro Cane\nPaul Balmer\nJelena Vojicic\nPaula Peyrani\nRay FarkouhACIP economics review team\nFangjun Zhou\nBo-Hyun Cho\nJamie Pike\nReni Kaul\nXiaoyu Dong\nSofia Bletnitsky\nAndrew Leidner\nTursynbek Nurmagambetov\n1. Altawalbeh  SM, Wateska AR, Nowalk  MP, Lin CJ, Harrison LH, Schaffner W, Zimmerman RK, Smith KJ. 2024. Cost -effectiveness of \nan in -development adult -formulated 21 -valent pneumococcal conjugate vaccine in US adults aged 50 years or older. Vaccine . Apr \n30;42(12):3024 -32.\n2. Atkinson AB. 1970.  On the measurement of inequality. Journal of Economic Theory . Sep 2;2(3):244 -63. \n3. Leidner AJ. 2024. Summary of three economic analyses on the use of 21 -valent pneumococcal conjugate vaccine (PCV21) among \nadults in the United States. Meeting of the Advisory Committee on Immunization Practices (ACIP),  June 26 -28, 2024.\n4. Yang F, Angus C, Duarte A, Gillespie D, Walker S, Griffin S. 2020. Impact of socioeconomic differences on distributional cost -\neffectiveness analysis. Medical Decision Making . Jul;40(5):606 -18.References\n23", "summary": "Summary of three economic analyses on the use of  PCVs among 50-64 year old  adults in the United States Andrew J. Leidner, Sofia Bletnitsky Applied Research, Implementation Science and Evaluation (ARISE) Branch Immunization Services Division (ISD) NCIRD ACIP Meeting October 23, 2024NCIRD/ISD/ARISE Disclaimer: Views and opinions expressed in this presentation are the authors and do not necessarily represent the views and opinions of the  Centers for Disease Control and Prevention .1 •This…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-23-24-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/03-Leidner-Pneumococcal-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 23}
{"title": "04 Kobayashi Pneumococcal 508", "content": "Summary of Work Group Interpretation of EtR and \nPolicy Options\nPCV Use in Adults aged ≥50 years\nOctober 23, 2024\nMiwako Kobayashi, MD, MPHNational Center for Immunization and Respiratory Diseases\n1\nPICO for WG discussion through October 2024\nCMC=chronic medical conditions (i.e., alcoholism; chronic heart disease, including congestive heart failure and cardiomyopath ies; chronic liver disease; chronic lung disease, including \nchronic obstructive pulmonary disease, emphysema, and asthma; cigarette smoking; or diabetes mellitus); IC=immunocompromising  condition(i.e., chronic renal failure, nephrotic \nsyndrome, immunodeficiency, iatrogenic immunosuppression, generalized malignancy, HIV infection, Hodgkin disease, leukemia, l ymp homa, multiple myeloma, solid organ transplant, \ncongenital or acquired asplenia, or sickle cell disease or other hemoglobinopathies). Those with a cerebrospinal fluid leak a nd a cochlear implant are also included among those with a \nrisk-based vaccine indication. Policy question: Should a single dose of pneumococcal conjugate vaccine (PCV) be recommended \nfor all PCV -naïve adults aged 50 –64 years? \nPopulation PCV-naïve adults aged 50 –64 years in the United States\nIntervention One dose of PCV15*, PCV20, or PCV21\n*In series with PPSV23\nComparison Current risk -based vaccine recommendation (CMC or IC)\nOutcomes Vaccine type (VT) -IPD, VT -non-bacteremic  pneumococcal pneumonia, VT -\npneumococcal mortality, serious adverse events\nEvidence to Recommendations ( EtR) framework  \n3EtR Domain Question\nPublic Health Problem • Is the problem of public health importance?\nEquity • What would be the impact of the intervention on health equity?\nBenefits and Harms • How substantial are the desirable anticipated effects?\n• How substantial are the undesirable anticipated effects?\n• Do the desirable effects outweigh the undesirable effects?\n• What is the overall certainty of this evidence for the critical outcomes?\nValues • Does the target population feel the desirable effects are large relative to the \nundesirable effects?\n• Is there important variability in how patients value the outcomes?\nAcceptability • Is the intervention acceptable to key stakeholders?\nResource Use • Is the intervention a reasonable and efficient allocation of resources?\nFeasibility • Is the intervention feasible to implement?\nPublic Health Problem\nIs pneumococcal disease of public health importance for adults aged 50 –64 years? \n4\n051015202530354045\n2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022Cases per 100,000 population\nYearAge <5 Age ≥65Invasive pneumococcal disease (IPD) incidence rates, by age \ngroup, 2007 –2022\nSource: CDC’s Active Bacterial Core surveillancePCV13: \nchildren\n5 Adapted from Gierke Feb 2024 ACIP meeting presentationPost -COVID\n051015202530354045\n2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022Cases per 100,000 population\nYearAge <5 Age 50-64 Age ≥65Invasive pneumococcal disease (IPD) incidence rates, by age \ngroup, 2007 –2022\nSource: CDC’s Active Bacterial Core surveillancePCV13: \nchildren\n6 Adapted from Gierke Feb 2024 ACIP meeting presentationPost -COVID\n051015202530354045\n2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022Cases per 100,000 population\nYearAge <5 Age ≥65Invasive pneumococcal disease (IPD) incidence rates, by age \ngroup, 2007 –2022\nSCDM: shared clinical decision -making\nSource: CDC’s Active Bacterial Core surveillancePCV13: adults \n65+PCV13: \nchildren\n7PCV13: adults 65+ \nbased on SCDM\nAdapted from Gierke Feb 2024 ACIP meeting presentationPost -COVID\nIPD mortality rate* in adults  aged ≥65 years has \nbecome closer to that in adults aged 50 –64 years \nABCs Bact  Facts Interactive Data Dashboard | ABCs | CDC . *deaths from IPD per 100,000 population 8\n\nAdults aged 50 –64 years at increased risk of \npneumococcal disease\n•Among adults aged 50 –64 years with pneumococcal disease (IPD1, \nhospitalized pneumococcal pneumonia2), a high proportion (88%) of adults \nhad ≥1 condition with a risk -based pneumococcal vaccine indication (risk \ncondition)\n1. CDC ABCs 2018 –2021 data\n2. Self et al. PNEUMO study unpublished data 9\nIs pneumococcal disease of public health importance?\n•Success of pediatric PCV program \nincreased the relative burden of \npneumococcal disease in adults aged 50 –\n64 years, especially in those with risk \nconditions*. \n•Additional Work Group comment:\n-Should consider the absolute rate of disease \n(rather than relative burden compared with \nother age groups). IPD rates have come \ndown significantly compared with pre -PCV \nera rates.\n*Adults with certain underlying medical conditions or other risk factors 10□ No \n□ Probably no  \n□ Probably yes  \n□ Yes \n□ Varies  \n□ Don’t know   \nEquity\nWhat would be the impact of recommending PCV for all PCV -naïve adults \naged 50 –64 years on health equity?\n11\nAbout 32–54% of adults aged 50 –64 years have underlying \nconditions with risk -based pneumococcal vaccine indication* \nSource: NHIS 2020 data\n*chronic heart disease, chronic lung disease, chronic liver disease, diabetes, smoking, alcoholism, weakened immune system du e to prescriptions, weakened immune system due to \nhealth condition, solid cancer (not including non -melanoma skin cancer or unknown type of skin cancer) and blood cancer 120%10%20%30%40%50%60%70%80%90%100%\nAge 50-64 years Age 65+ yearsHispanic\nWhite, non-Hispanic\nBlack, non-Hispanic\nAsian, non-Hispanic\nDisparities in pneumococcal vaccine coverage by race/ethnicity exist \nfor both age -based and risk -based indications\nSource: BRFSS 2022; AI/AN=American Indian and Alaska Native 130102030405060708090100\n50-64 years, risk-based 65+ yearsPercentHispanic\nWhite, non-Hispanic\nBlack, non-Hispanic\nAsian, non-Hispanic\nAI/AN, non-Hispanic\n05101520253035\n40-44 45-49 50-54 55-59 60-64 65+ 40-44 45-49 50-54 55-59 60-64 65+\nBlack Black Black Black Black Black Non\nBlackNon\nBlackNon\nBlackNon\nBlackNon\nBlackNon\nBlackIPD rates (any pneumococcal serotype) in Black adults peak \nat a younger age compared with Non -Black adults\nABCs 2018 –2019 unpublished data 14IPD rate for adults aged ≥65 years across all \nrace/ethnicity (24/100,000)\nImpact of hypothetical PCV20/PCV21 vaccination scenarios on \nnon-PCV13 -type IPD rates in adults aged ≥19 years\nCDC ABCs 2014 –2019 unpublished data. 15\n2 3\nVaccination Scenarios•For simplicity, assumes vaccine \nprotects against 100% of vaccine -\ntype disease\n•Vaccine coverage is applied to \nadults who developed non -\nPCV13 -type IPD in 2014 –2019 (American Indian and Alaska Native)\n\nImpact of hypothetical PCV20/PCV21 vaccination scenarios on \nnon-PCV13 -type IPD rates in adults aged ≥19 years\nCDC ABCs 2014 –2019 unpublished data. 16\n2 3\nVaccination Scenarios(American Indian and Alaska Native)\nVaccination Scenarios:\n1.Current risk -based (19 –64 years) \nand age -based (≥65 years) \nrecommendations with observed \nvaccine coverage by race\n• For simplicity, assumes vaccine protects \nagainst 100% of vaccine -type disease\n• Vaccine coverage is applied to adults who \ndeveloped non -PCV13 -type IPD in 2014 –2019 1 1Population \naverage\nImpact of hypothetical PCV20/PCV21 vaccination scenarios on \nnon-PCV13 -type IPD rates in adults aged ≥19 years\nCDC ABCs 2014 –2019 unpublished data. 17\n2 3\nVaccination Scenarios(American Indian and Alaska Native)\n1 1Vaccination Scenarios:\n1.Current risk -based and age -based \nrecs with observed vaccine \ncoverage by race\n2.Lower age -based recs to ≥50 years \nusing current coverage for adults \naged ≥65 years; risk -based for 19 –\n49 years2 2\nWhat would be the impact of recommending PCV for all PCV -\nnaïve adults aged 50 –64 years on health equity?\n18□ Reduced\n□ Probably reduced  \n□ Probably no impact  \n□ Probably increased\n□ Increased   \n□ Varies \n□ Don’t know \nWork Group comments\n•The intervention could help improve health equity by:\n-Improving vaccine coverage for those with known or unknown risk conditions\n-Providing protection at an earlier age when certain populations (e.g., Black \nadults, AI adults) are already experiencing elevated disease rates\n-Simplifying the recommendation, which could improve implementation across all \npopulations\n•Acknowledged that the overall impact on health equity is complex and \nwould depend on how the recommendation is implemented and any \nunderlying disparities in healthcare access.\n19\nBenefits and Harms\n20\nOutcomes considered were specified in PICO\n*Rated on a 1 to 9 scale, where 7 –9 are critical, 4 –6 are important, 1 –3 are of limited importance 21Outcome (Benefits) Importance* Data sources\nVT-IPD Critical\nPCV clinical trial data (immunogenicity)VT-non-bacteremic  \npneumococcal pneumoniaCritical\nVT-pneumococcal deaths Critical\nSerious adverse events \n(SAE)Critical PCV clinical trial data; post -licensure \nsafety data (PCV20)\nUpdated targeted literature search \n•Previously conducted systematic review of literature and presented \nsummary of findings and GRADE for PCV151, PCV202, PCV213\n•Updated literature search (August and September, 2024) based on current \nPICO question\n•6 PCV15 trials, 3 PCV20 trials, and 7 PCV21 trials included in the updated \nreview (list of studies available in supplemental slides) \n1. Presented summary of literature search through February 18, 2021\n2. Presented summary of literature search through March 31, 2022\n3. Presented summary of literature search through October 17, 202322\nPCV clinical trial data (immunogenicity)\nConclusions remain unchanged\n•PCV15: Noninferior1 to PCV13 for all shared serotypes; had statistically significantly \ngreater response2 for non -PCV13 serotypes 22F and 33F vs. PCV13\n•PCV20: Noninferior3 to PCV13 for all shared serotypes; noninferior3 to PPSV23 for \n6/7 non -PCV13 serotypes (not met for serotype 8)\n•PCV21: Noninferior4 to PCV20 for 10/10 shared serotypes; had statistically \nsignificantly greater response5 for 10/11 PCV21 -unique serotypes (except serotype \n15C) \n1. Noninferiority defined as the lower bound of the 2 -sided 95% CI of the OPA GMT ratio (PCV15/PCV13) to be >0.5. \n2. Statistically significantly greater response for unique serotypes (22F and 33F) defined as the lower bound of the 2 -sided 95% CI of the OPA GMT ratio (PCV15/PCV13) to be >2.0 and the lower bound of \nthe 2 -sided 95% CI of the differences (PCV15 -PCV13) between the proportions of participants with a ≥4 -fold rise to be >0.1 (or 1 0 percentage points)\n3. Noninferiority for a serotype was declared if the lower bound of the 2 -sided 95% CI for the OPA GMT ratio (PCV20/comparator vacci ne) for that serotype was greater than 0.5 (2 -fold criterion).\n4. Noninferiority for GMT ratio was defined as the lower bound of the 2 -sided 95% CI of the OPA GMT ratio [PCV21 / (Comparator Vacc ine)] to be >0.5.\n5. Statistically significantly greater response for GMT ratio was defined as the lower bound of the 2 -sided 95% CI of the OPA GMT r atio [PCV21 / (Comparator Vaccine)] to be >2.0. Statistically significantly \ngreater response for difference in proportions of participants with a ≥4 -fold rise in serotype -specific OPA responses from basel ine to 30 days postvaccination was defined as the lower bound of the 2 -\nsided 95% CI of the differences [PCV21 – (Comparator Vaccine)] between the proportions of participants with a ≥4 -fold rise from baseline to 30 days postvaccination to be >0.1. 23\n1. How substantial are the desirable  anticipated \neffects* of PCV vaccination?\nIntervention: Recommending PCV for all PCV -naïve adults aged 50 –64 years\nComparator: Risk-based recommendation for adults with CMC/IC\nCMC: chronic medical conditions, IC=immunocompromising conditions 24□ Minimal\n□ Small  \n□ Moderate  \n□ Large  \n□ Varies  \n□ Don’t know   *Desirable anticipated effects for the following outcomes \nas specified in the PICO:\nVaccine -type (VT) IPD, VT non -bacteremic  pneumococcal \npneumonia, VT pneumococcal mortality\nCertainty of evidence (February 2024 ACIP meeting): \nModerate \nPCV clinical trial data (safety)\nConclusions remain unchanged\n•No vaccine -related serious adverse events reported for PCV15 and PCV20\n•Two vaccine -related serious adverse events reported among PCV21 \nrecipients (previously presented)\n-Bronchospasm (V116 -005): 50 -year -old female in the sequential group with \nbronchospasm within 30 minutes after the 2nd vaccination (V116); duration 23 \nhours; resolved \n-Injection site cellulitis (V116 -006): 67 -year -old female in Cohort 1 (prior PPSV23) \nwith injection site cellulitis on Day 6; duration 1.57 weeks; resolved\n25\nPost -licensure PCV20 safety data\nWhat we presented during the February 2024 ACIP meeting\n•October 2021 –December 2023: 1,976 VAERS reports after PCV20 in adults*\n•Most reports were classified as non -serious \n•Data mining alert for disproportional reporting of Guillain -Barré Syndrome (GBS) \nafter PCV20 vaccine\n•11 reports  for GBS after PCV20 vaccine, verified by chart review\n•The reporting rate for GBS after PCV20 vaccine was  0.5 cases  per million doses distributed \n•FDA also presented preliminary FDA -CMS partnership data at the meeting\n•Near real -time monitoring in Medicare beneficiaries aged ≥65 years had not identified a \nsafety signal for GBS\n*adults defined as individuals aged ≥19 years 26\nPost -licensure PCV20 safety data\nUpdated data\n•October 2021 –August 2024 : 2,767 VAERS reports after PCV20 in adults*\n•18 reports for Guillain -Barré Syndrome (GBS) after PCV20 vaccine, verified by chart \nreview\n•The reporting rate for GBS after PCV20 vaccine was  0.7 cases per million doses \ndistributed \n•Updated  data findings from FDA-CMS partnership ( data through May 31, 2024 )\n•A statistically significant signal (IRR>1†) for GBS following PCV20 vaccination in Medicare \nbeneficiaries aged ≥65 years identified when using the primary GBS definition\n•GBS events were not chart confirmed (based on claims)\n•Findings were not statistically significant when using a different GBS definition or \nadjusting for positive predictive value \n•Incidence was low (<10 GBS cases per 100K person -years), resulting in wide \ncredible intervals \n*adults defined as individuals aged ≥19 years\n†Bayesian Poisson Regression was used to estimate the posterior distribution of incidence rate ratio (IRR) between pre -specified risk and comparison windows 27\nSummary: Post -licensure PCV20 safety data\n•Potential Guillain -Barré Syndrome (GBS) signal for PCV20 in VAERS\n•GBS signal in Medicare sequential monitoring for primary definition, but \nnot for alternate definition or when adjusted for positive predictive value\n•Significant uncertainty because of the small number of GBS cases \nobserved\n•CDC and FDA will continue to monitor post -licensure PCV safety\n28\n2. How substantial are the undesirable  anticipated \neffects* of PCV vaccination?\nIntervention: Recommending PCV for all PCV -naïve adults aged 50 –64 years\nComparator: Risk-based recommendation for adults with CMC/IC\nCMC: chronic medical conditions, IC=immunocompromising conditions 29□ Minimal\n□ Small  \n□ Moderate  \n□ Large  \n□ Varies  \n□ Don’t know   *Desirable unanticipated effects for the following \noutcome as specified in the PICO: Serious adverse events\nCertainty of evidence (February 2024 ACIP meeting): \nModerate \n3. Do the desirable  effects of PCV vaccination outweigh the \nundesirable  anticipated effects?\nIntervention: Recommending PCV for all PCV -naïve adults aged 50 –64 years\nComparator: Risk-based recommendation for adults with CMC/IC\nCMC: chronic medical conditions, IC=immunocompromising conditions 30□ Favors intervention\n□ Favors current (risk -based for CMC/IC only) \n□ Favors both   \n□ Favors neither  \n□ Varies  \n□ Don’t know   Additional Work Group comment:\n•Some members believed that \nthe interpretation would vary \nby the PCV product\nValues and Preferences   \n31\n1. Does the target population feel that the desirable \neffects are large relative to undesirable effects?\n32□ No \n□ Probably no  \n□ Probably yes  \n□ Yes \n□ Varies  \n□ Don’t know   \nWork Group comments\n•Members with experience serving underserved populations, with many \nunderinsured or self -pay individuals, noted that these groups can be comfortable \nwith pneumococcal vaccines if benefits are clearly explained.\n•The effectiveness of communication about benefits depends significantly on who \ndelivers the message and how much time is spent explaining it.\n•There was discomfort in asserting what the target population thinks without more \nevidence.\n•Average populations may prioritize concerns about undesirable effects over \nperceived benefits.\n•Increased vaccine hesitancy observed in recent times makes the interpretation \nchallenging.\n33\n2. Is there important uncertainty about or variability \nin how much people value the main outcomes*?\n*Vaccine -type (VT) IPD, VT -non -bacteremic  pneumococcal pneumonia, VT -pneumococcal deaths, serious adverse events 34□ Important uncertainty or variability \n□ Probably important uncertainty or variability\n□ Probably not important uncertainty or variability \n□ No important uncertainty or variability \n□ No known undesirable outcomes\nAcceptability\nIs the intervention acceptable to key stakeholders?\n35\nIs it acceptable to recommend PCV for all PCV -naïve \nadults aged 50 –64 years? \n•At the June ACIP meeting, presented \nfindings from Merck -funded healthcare \nprovider surveys1,2:\n-challenges with implementing risk -based \nvaccine recommendations (e.g., time \nconstraints, difficulties in identifying \nvaccination history or underlying health \ncondition of the patient)\n-support for lowering the age threshold of \nthe current age -based recommendation\n1. Online survey conducted in February 2024 by ZS, funded by Merck. 502 HCPs (physicians, NP/PAs, pharmacists who vaccinate) par ticipated; majority (70%) physicians\n2. Online survey conducted from March –May 2024 by OPEN Health, funded by Merck. Included a total of 340 HCPs consisting of physicia ns, nurse practitioners, physician assistants, \nand pharmacists36□ No \n□ Probably no  \n□ Probably yes  \n□ Yes \n□ Varies  \n□ Don’t know   \nResource Use\nIs the intervention a reasonable and efficient allocation of resources?\n37\nSummary of model findings, “adding” strategies \n38•From the “adding” comparisons, all strategies improved health, but none were cost -saving​\n•Cost per QALY gained estimates for PCV20 had a wider range, more uncertainty than PCV21​\n•In two of three models, PCV21 had lower costs per QALY gained than PCV20​\nLeidner October 2024 ACIP meeting presentation 0 100,000 200,000 300,000 400,000 500,000 600,000 700,000 800,000 900,000 1,000,000\nIncermental cost -effectiveness ratio (ICER) ($/QALY)Cost -effectiveness estimates for PCV21 and PCV20 vaccination at age 50 \nand 65 years vs. current recommendations\nPCV21\nPCV21PCV20\nPCV20\nPCV20Tulane -CDC \nMerck \nmodel\nPfizer \nmodel\nIs PCV use for PCV -naïve adults aged 50 –64 years a reasonable \nand efficient allocation of resources?\n39□ No \n□ Probably no  \n□ Probably yes  \n□ Yes \n□ Varies  \n□ Don’t know   •Probably yes/yes:\n-Despite the higher economic costs, \nmembers valued the opportunity to \nprevent more disease, particularly among \nracial and ethnic groups who currently have \nhigher disease burden \nWork Group comments\nProbably No/Varies:\n•Some Work Group members expressed concerns about the less favorable \neconomic analysis for PCV20 compared to PCV21 .\n•Improved vaccination coverage among those with risk -based pneumococcal \nvaccine indications could diminish the need for broader age -based \nvaccination, while acknowledging that there has been insufficient success \n•The decision varies when considering projections over the next 15 years, \ne.g., indirect effects of pediatric vaccination, availability of new higher -\nvalency vaccines, data on duration of protection from vaccination, and \nconsiderations of whether or not to give booster doses.\n40\nFeasibility\nIs the intervention feasible to implement?\n41\nIs it feasible to implement PCV for all PCV -naïve adults \naged 50 –64 years? \n42□ No \n□ Probably no  \n□ Probably yes  \n□ Yes \n□ Varies  \n□ Don’t know   \nVaccine coverage tends to be lower in younger adults \neven with an age -based recommendation\n1.Week ending May 11, 2024. Vaccine coverage with the updated 2023 -2024 COVID -19 vaccine, defined as receipt of at least one vacci nation since September 2023.\n2.Week ending May 11, 2024. Vaccine coverage for the 2023 -2024 influenza season\n3.Vaccination Coverage among Adults in the United States, National Health Interview Survey, 2021 | CDC , % represents those who received at least 2 doses\n4.BRFSS 2022 data, % represents receipt of any pneumococcal vaccine dose 4350–64 yrs ≥65 yrs\nCOVID -19125.2% 40.6%\nInfluenza251.5% 73.8%\nRecombinant \nZoster Vaccine312.2% (50 –59) 20.1% (60 –64) 22.8%\nPneumococcal437.3%* 69.7%\n*Receipt of any pneumococcal vaccine dose among those with risk -based indications\nCompared with vaccine coverage in adults aged ≥65 years, \npneumococcal vaccine coverage in adults aged 50 –64 years \nwith risk -based indication was disproportionately lower\n1.Week ending May 11, 2024. Vaccine coverage with the updated 2023 -2024 COVID -19 vaccine, defined as receipt of at least one vacci nation since September 2023.\n2.Week ending May 11, 2024. Vaccine coverage for the 2023 -2024 influenza season\n3.Vaccination Coverage among Adults in the United States, National Health Interview Survey, 2021 | CDC , % represents those who received at least 2 doses\n4.BRFSS 2022 data, % represents receipt of any pneumococcal vaccine dose 4450–64 yrs ≥65 yrs (50–64 yrs)/\n(≥65 yrs)\nCOVID -19125.2% 40.6% 0.62\nInfluenza251.5% 73.8% 0.70\nRecombinant \nZoster Vaccine312.2% (50 –59) 20.1% (60 –64) 22.8%\nPneumococcal437.3%* 69.7% 0.54\n*Receipt of any pneumococcal vaccine dose among those with risk -based indications\nWork Group comments\n•Age-based recommendations are generally easier to implement than risk -\nbased recommendations \n•Lower vaccine coverage in younger adults is likely due to multiple factors, \nsuch as healthcare access, perceived risk of disease or benefits from \nvaccination.\n-There is a larger proportion of adults aged 50 –64 years without health insurance \ncompared with adults aged ≥65 years1.\n•Having a different age -based recommendation by vaccine product (e.g., \nPCV20, PCV21) will be more challenging to implement. \n•Variability in health insurance coverage might keep PCV20 as the only \npractical option for some individuals in the short term since PCV21 is new.\n1. Health Insurance Coverage in the United States: 2022 (census.gov) 45\n46EtR Domains Work Group Interpretation\nPublic Health Problem Yes\nEquity Probably increased\nBenefits and Harms\na. Benefits Moderate\nb. Harms Minimal\nc. Benefit>Harm? Favors intervention\nValues and Preferences\na. Desirable>Undesirable? Probably yes/yes\nb. Uncertainty? Probably not important uncertainty or variability\nAcceptability Yes\nResource Use Probably yes/Yes\nFeasibility Probably yes/YesSummary of Work Group Interpretations of EtR Domains\nKey considerations: factors supporting lowering the \nPCV age -based recommendation to age ≥50 years\n1.The relatively high burden of pneumococcal disease in adults aged 50 –64 years, \nparticularly among those with risk conditions\n2.Potential for improved vaccine uptake through an age -based recommendation, \nwhich is easier to implement compared with the current risk -based \nrecommendation\n3.Potential to reduce pneumococcal disease incidence  in demographic groups \nexperiencing the highest burden\n4.Projected health benefits from economic models* despite increased net costs\n*Note that these are models that assumed that another vaccine dose is given later in life to ensure older adults are protecte d from disease 47\nKey considerations: potential implications\n1.Economic concerns: While our models showed health benefits, there were \nsignificant concerns about the cost of lowering the age recommendation for both \nPCV20 and PCV21 when considering overall health benefits to society \n2.Market availability and insurance coverage: Concerns were raised that variability \nin health insurance coverage might keep PCV20 as the only practical option for \nsome individuals in the short term, given that PCV21 is a newer vaccine\n3.Ease of implementation: The Work Group agreed that having different age -based \nrecommendations by vaccine would be challenging to implement\n48\nKey considerations: uncertainties\n1.How long is the duration of protection from a dose of PCV in adults?\n \n2.What is the magnitude of indirect effects from pediatric PCV15/20 vaccination? \n3.What might be the impact of higher -valency vaccines under development?\n49\nSummary: Work Group Interpretation\n•Should a single dose of pneumococcal conjugate vaccine be \nrecommended for all PCV -naïve adults aged 50 –64 years? \n50Balance of \nconsequencesUndesirable \nconsequences \nclearly \noutweigh \ndesirable \nconsequences \nin most \nsettingsUndesirable \nconsequences \nprobably \noutweigh \ndesirable \nconsequences \nin most \nsettingsThe balance \nbetween \ndesirable and \nundesirable \nconsequences \nis closely \nbalanced or \nuncertainDesirable \nconsequences \nprobably \noutweigh \nundesirable \nconsequences \nin most \nsettingsDesirable \nconsequences \nclearly \noutweigh \nundesirable \nconsequences \nin most \nsettingsThere is \ninsufficient \nevidence to \ndetermine the \nbalance of \nconsequences\nShould a single dose of pneumococcal conjugate vaccine be \nrecommended for all PCV -naïve adults aged 50 –64 years? \nIs there sufficient information to move forward with a recommendation\nYes\n•Policy options for ACIP consideration\n-The majority recommended, but about a quarter said “do not recommend the \nintervention”\n•The higher cost/QALY gained for PCV20 compared to PCV21 in economic \nanalyses\n•Uncertainties around key assumptions like the impact of pediatric PCV use \nand duration of protection\n•Concerns about the implications of a broad recommendation given the \ndifferences in serotype coverage between PCV20 and PCV21\n51\nShould a single dose of pneumococcal conjugate vaccine be \nrecommended for all PCV -naïve adults aged 50 –64 years? \n•Is there sufficient information to move forward with a recommendation\n-Yes\n•Policy options for ACIP consideration\n-Recommend the intervention \n52\nProposed policy option \n•ACIP recommends a pneumococcal conjugate vaccine (PCV) for all PCV -\nnaïve adults aged ≥50 years\n53\nClinical considerations\nProposed language\n54\nPCV-naïve adults* (or adults with unknown history)\n•A single dose of PCV (PCV15, PCV20, or PCV21) is recommended for all \nadults aged ≥50 years and for adults aged 19 –49 years with certain \nunderlying conditions or risk factors†who have not received a PCV or \nwhose vaccination history is unknown. \n•If PCV15 is administered, a single dose of PPSV23§ should be \nadministered ≥1 year after the PCV15 dose. A minimum interval of 8 \nweeks can be considered if PCV15 is used in adults with an \nimmunocompromising condition¶, cochlear implant, or CSF leak.\n*Includes adults who received PCV7 only\n†Alcoholism; chronic heart, liver, or lung disease; chronic renal failure; cigarette smoking; cochlear implant; congenital or acquired asplenia; cerebrospinal fluid leak; diabetes mellitus; \ngeneralized malignancy; HIV; Hodgkin disease; immunodeficiency; iatrogenic immunosuppression; leukemia, lymphoma, or multiple  myeloma; nephrotic syndrome; solid organ \ntransplant; sickle cell disease; or other hemoglobinopathies.\n§For adults who have received PCV15 but have not completed their recommended pneumococcal vaccine series with PPSV23, 1 dose o f PCV21 or PCV20 may be used if PPSV23 is not \navailable.\n¶Chronic renal failure, nephrotic syndrome, immunodeficiency, iatrogenic immunosuppression, generalized malignancy, HIV infect ion, Hodgkin disease, leukemia, lymphoma, multiple \nmyeloma, solid organ transplant, congenital or acquired asplenia, or sickle cell disease or other hemoglobinopathies .55DRAFT\nUnderlying \nconditionsPrevious \nvaccination \nhistoryAge 19 –49 years Age ≥50 years\nNone None No vaccine recommendation\nChronic \nmedical \nconditionsNone\nCSF leak, \ncochlear \nimplantNone \nImmuno -\ncompromisedNonePCV15 PPSV23*OR\n≥1yr\nUse of 21 -Valent Pneumococcal Conjugate Vaccine Among U.S. Adults: Recommendations of the Advisory Committee on Immunization Pra ctices — United States, 2024 | MMWR 56*If adults previously received PPSV23 before receiving a dose of PCV15, it need not be followed by another dose of PPSV23\n†A minimum interval of 8 weeks can be considered for adults with an immunocompromising condition, cochlear implant, or cerebro spinal fluid \nleakPCV20ORPCV21\nPCV15 PPSV23*ORPCV20ORPCV21\n≥1yr≥8wks†PCV-naïve adults (or adults with unknown history) DRAFT\nPCV13 -experienced adults who completed  the \nrecommended vaccine series\n•Shared clinical decision -making is recommended regarding use of a \nsupplemental PCV20 or PCV21 dose for adults aged ≥65 years who have \ncompleted their recommended vaccine series with both PCV13 and \nPPSV23.\nRationale:\n•No change is proposed to the age threshold. Under the previous \nrecommendation, PCV13 -vaccinated adults were only considered to have \n“completed” their recommended vaccine doses after receiving one and \nfinal dose of PPSV23 at or after age 65 years . Therefore, this scenario only \napplies to adults aged ≥65 years who received both PCV13 and PPSV23 at \nor after age 65 years. 57DRAFT (no change from current)\nUnderlying conditions Age ≥65 years\nNone\nChronic medical \nconditions\nCSF leak, cochlear \nimplant\nImmuno -compromisedPCV13 -experienced adults who completed  the \nrecommended vaccine series\nUse of 21 -Valent Pneumococcal Conjugate Vaccine Among U.S. Adults: Recommendations of the Advisory Committee on Immunization Pra ctices — United States, 2024 | MMWR58PCV13 PPSV23\n≥1yr≥8wks*\nPCV20ORPCV21\nShared clinical \ndecision -makingDRAFT (no change from current)\n≥5yrs\n*A minimum interval of 8 weeks can be considered for adults with an immunocompromising condition, cochlear implant, or cerebr ospinal fluid leak\nPCV13 -experienced adults who have not completed \nthe recommended vaccine series\n•A single dose of either PCV20 or PCV21 is recommended for adults aged \n≥19 years who have started their pneumococcal vaccine series with PCV13 \nbut have not received all recommended pneumococcal vaccine doses.\nChange:\n•Removed the option to complete vaccine series with PPSV23 for PCV13 -\nexperienced adults\nRationale:\n•The potential need for repeated PPSV23 doses in adults who received \nPCV13 was one of the reasons for the complexity of the recommendation. \n59DRAFT\nUnderlying \nconditionsAge 19 –64 years Age ≥65 years\nNone\nChronic \nmedical \nconditions\nCSF leak, \ncochlear \nimplant\nImmuno -\ncompromised≥8wksPCV13 -experienced adults who have not completed the \nrecommended vaccine series (current recommendation)\n60≥5yrs≥5yrs≥1yr\nOR\nPCV13PCV13\nPCV13PCV13\nPPSV23\nPPSV23 PPSV23PPSV23≥1yr PCV20PCV21\nOR\nOR\nPCV20PCV21\nOR\nPPSV23PCV20PCV21\nOR\nOR≥8wksOR\nUnderlying \nconditionsAge 19 –64 years Age ≥65 years\nNone\nChronic \nmedical \nconditions\nCSF leak, \ncochlear \nimplant\nImmuno -\ncompromised≥8wksPCV13 -experienced adults who have not completed \nthe recommended vaccine series (proposed)\n61≥5yrs≥5yrs≥1yr\nOR\nPCV13PCV13\nPCV13PCV13\nPPSV23\nPPSV23 PPSV23PPSV23≥1yr PCV20PCV21\nOR\nOR\nPCV20PCV21\nOR\nPPSV23PCV20PCV21\nOR\nOR≥8wksOR\nAcknowledgements\n•ACIP and the Pneumococcal Vaccines Work Group\n•Active Bacterial Core surveillance sites and program\n•Charles Stoecker, Yin Wang (Tulane University)\n•Wesley Self, Jackson Resser (Vanderbilt University Medical Center)\n•CDC contributors and consultants: Ryan Gierke, Jennifer Farrar, Andrew Leidner, \nSofia Bletnitsky, Kristin Andrejko, Emma Accorsi, Wei Xing, Adam Cohen, Alison \nAlbert, Shelby Miller, Noele Nelson, Kimberly Fox, Pedro Moro, Bo -Hyun Cho, \nElizabeth Velazquez, Janelle King, Fangjun Zhou, Peng -Jun Lu, Anup Srivastav, Carla \nBlack, Marc Fischer, Laurie Orell, Cheryl Ward, Rebecca Morgan, Doug Campos -\nOutcalt\n62\nSupplementary Slides\n63\nSearch strategy\n64Database Strategy Run Date Records\nPubMed (PCV15 OR PCV20 OR \"15 -valent pneumococcal \nconjugate vaccine\" OR \"20 -valent pneumococcal \nconjugate vaccine\") AND adult; Filters applied: English, \nHumans, from 2021/2/19 - Present. August 3, 2024 94\nPubMed (PCV21 OR V116 OR \"pneumococcal conjugate vaccine \n21\" OR \"pneumococcal conjugate vaccine 21 -valent\") \nAND (\"2023/09/19\"[Date - Publication] : \"3000\"[Date - \nPublication])September 8, \n202466\nClinicaltrials.gov V114, Filter: \"Adult (18 -64)\", \"Phase 3\" August 17, 2024 8\nClinicaltrials.gov 20vPnc, PCV20, 20 -valent PCV, 20 -valent pneumococcal \nconjugate vaccine; Filter: \"Adult (18 -64)\", \"Phase 3\" August 17, 2024 18\nClinicaltrials.gov 1. Intervention: “V116”, filter: “Adult (18 –64)”, “Phase \n3” \n2. “PCV21”, filter: “Adult (18 –64)”, “Phase 3”\n3. “21 valent pneumococcal conjugate vaccine”, filter: \n“Adult (18 –64)”, “Phase 3”September 8, \n20241. 7\n2. 0\n3. 7 (all duplicate \nwith 1)\nStudy Study designCountry (or \nmore detail, if \nneeded)Age (rangeTotal \npopulationN Intervention N comparison OutcomesFunding \nsource\nSong 2021Phase III randomized \ncontrolled trial US, Korea, \nSpain, TaiwanAdults ≥50 years of \nage, PCV followed by \nPPSV23 12 months \nlater627 325 302Immunogenicity,\nSafetyMerck\nMohapi  2022Phase III randomized \ncontrolled trial USAdults ≥18 years of \nage with HIV, PCV \nfollowed by PPSV23 8 \nweeks later298 150 148Immunogenicity,\nSafetyMerck\nPlatt 2022Phase III randomized \ncontrolled trialUS, Japan, \nSpain, Canada, \nTaiwanAdults ≥50 years of \nage1202 602 600Immunogenicity,\nSafetyMerck\nSimon 2022Phase III randomized \ncontrolled trialUS, Australia, \nChile, Denmark, \nFinland, UKAdults ≥50 years of \nage2340 2107 233 Immunogenicity,  Safety Merck\nSeverance 2022Phase III randomized \ncontrolled trialUSAdults ≥50 years of \nage1200600 (concomitant \nwith QIV)600 (sequential QIV \nadministration)Immunogenicity, Safety Merck\nV110 -911Phase III randomized \ncontrolled trialUS, Puerto RicoAdults ≥50 years of \nage850 (includes 426 \nwho received \nPPSV23 214 (concomitant \nwith mRNA -1273)210 (sequential mRNA -\n1273 administration)Immunogenicity and \nsafetyMerckPCV15 studies included in the review of evidence\n65\nStudy Study designCountry (or \nmore detail, if \nneeded)Age (rangeTotal \npopulationN Intervention N comparison OutcomesFunding \nsource\nEssink , 2022Phase III \nrandomized \ncontrolled \ntrial US and \nSwedenAdults ≥ 18 -49 \nyears (34.0, SD \n8.8)448 336 (PCV20) 112 (PCV13)\nImmunogenicity,\nSafetyPfizerAdults ≥ 50 -59 \nyears (54.9, SD \n2.8)445 334 (PCV20) 111 (PCV13)\nAdults ≥ 60 \nyears (64.6, SD \n4.8)2997 1507 (PCV20)1490 \n(PCV13+PPSV23)\nHurley, 2021    Phase II \nrandomized \ncontrolled \ntrial  USAdults 60 - 64 \nyears (62.0, SD \n1.4)444 222 222Immunogenicity, \nSafetyPfizer\nHaranaka , 2024Phase III \nrandomized \ncontrolled \ntrialJapan, \nSouth \nKorea, and \nTaiwanAdults aged \n≥60 years (66.1, \nSD 4.7)1421 711 (PCV20)710 \n(PCV13+PPSV23)Immunogenicity, \nSafetyPfizerPCV20 studies included in the review of evidence\n66\nPCV21 studies included in the review of evidence\n*participants who received at least one dose of study intervention67Study Study design Country Age Total population N Intervention* N comparison OutcomesFunding \nsource\nPlatt, 2023 RCT (Phase II) US Adults ≥50 years 508 254 PPSV23: 254 Immunogenicity and SafetyMerck\nPlatt, 2024RCT (Phase III); \npivotal studyUS, Australia, Belgium, \nChile, Germany, Korea, \nNew Zealand, Puerto \nRico, Sweden, Taiwan, \nTurkeyHealthy adults ≥50 years, \npneumococcal vaccine – naïve\n2,6631,179 PCV20: 1,177\nImmunogenicity and Safety Merck\nHealthy adults 18 - 49 years, \npneumococcal vaccine – naïve200 PCV20:  100\nV116 -005RCT (Phase III)US Adults ≥50 years 1,080(V116 + QIV, \ncoadministered): 536(QIV followed by V116): \n536Immunogenicity and\nSafetyMerck\nScott, 2024RCT (Phase III)US, Canada, Israel, \nFrance, Italy, Japan, \nKorea, Spain, TaiwanAdults ≥50 years, previous PPSV23 \n≥1 year prior to enrollment350 229 PCV15, n=117\nImmunogenicity\nand\nSafetyMerckAdults ≥50 years, previous PCV13 ≥1 \nyear prior to enrollment261 174PPSV23\nN=85\nAdults ≥50 years, PCV13+PPSV23, \nPCV15+PPSV23, PCV15, PCV20, or \nPPSV23+PCV13 ≥1 year prior to \nenrollment106 105 None\nV116 -007 RCT (Phase III)Belgium,  Chile,  France,  \nSouth Africa,\nThailand,\nUnited StatesAdults ≥18 years living with HIV; 36% \nprior PCV13 or PPSV23*313 155 PCV15+PPSV23, n=156 Immunogenicity and Safety Merck \nV116 -008 RCT (Phase III)United States, Australia, \nCanada, Chile, Japan, \nSouth Korea, New \nZealand, Poland,  Adults aged 18 –64 years with \nincreased risk for pneumococcal \ndisease†518 386 PCV15+PPSV23, n=130 Immunogenicity and Safety Merck\nV116 -010 RCT (Phase III)Argentina, Australia, \nColombia, Germany, \nIsrael, South Korea, New \nZealand, Spain, Taiwan, \nTurkey, United KingdomAdults aged ≥50 years, \npneumococcal vaccine -naïve 1,484 739 PPSV23: 741 Immunogenicity and Safety Merck", "summary": "Summary of Work Group Interpretation of EtR and  Policy Options PCV Use in Adults aged ≥50 years October 23, 2024 Miwako Kobayashi, MD, MPHNational Center for Immunization and Respiratory Diseases 1 PICO for WG discussion through October 2024 CMC=chronic medical conditions (i.e., alcoholism; chronic heart disease, including congestive heart failure and cardiomyopath ies; chronic liver disease; chronic lung disease, including  chronic obstructive pulmonary disease, emphysema, and asthma;…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-23-24-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/04-Kobayashi-Pneumococcal-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 67}
{"title": "01 influenza Loehr 508", "content": "National Center for Immunization & Respiratory Diseases\nInfluenza Work Group —Introduction\nDr. Jamie Loehr (Work Group Chair)\nAdvisory Committee on Immunization Practices\nOctober 23, 2024\nInfluenza Work Group\nACIP Members\n•Jamie Loehr (Chair)\n•Robert Schechter\n•Albert Shaw\n•Keipp Talbot\nEx Officio\n•Timothy Brennan (FDA)\n•Uzo Chukwuma (IHS)\n•Michael Ison (NIH)\n•Cynthia Nolletti (FDA)\n•Jo Resnick (FDA)\n•Chris Roberts (NIH)Liaison Representatives and Consultants\n•Robert Atmar\n•Kevin Ault\n•Ed Belongia\n•Hank Bernstein\n•Kris Bryant\n•Doug Campos -Outcalt\n•Sarah Coles\n•Frances Ferguson\n•Sandra Fryhofer\n•Robert Hopkins\n•Wendy Keitel\n•Camille Kotton\n•Marie -Michèle Léger\n•Susan Lett\n•Krissy Moehling•Zackary Moore\n•Rebecca Morgan\n•Flor Munoz\n•Caitlin Newhouse\n•Jesse Papenburg\n•William Schaffner\n•Ken Schmader \n•Tamara Sheffield\n•Angela Sinilaite\n•Peter Szilagyi\n•Matthew Zahn\nCDC Lead\n•Lisa Grohskopf\n2\nCDC Participants\n•Lenee Blanton\n•Karen Broder\n•Alicia Budd\n•Jessie Chung\n•Jennifer DeCuir\n•Sascha Ellington\n•Tarayn Fairlie\n•Jill Ferdinands\n•Brendan Flannery\n•Andrew Kroger\n•Samantha Olson\n•David Shay\n•Tom Shimabukuro\n•Naomi Tepper\n3\nBrief Note\nUpdate concerning FluMist (Live Attenuated Influenza Vaccine, Trivalent; LAIV3)\n•On September 20, 2024, FDA approved FluMist for self or caregiver administration.\n•For the current 2024 -25 influenza season, FluMist is available for administration by \na healthcare provider only. \n•It is anticipated that FluMist will be available for self or caregiver administration for \nthe 2025 -26 influenza season.\n4https://www.fda.gov/vaccines -blood -\nbiologics/vaccines /flumist  \n2023 -24 Season Influenza Vaccine Effectiveness (VE)\nUpdates:\n•2023–24 End of Season Influenza Vaccine Effectiveness – United States\n⁻Dr. Sascha Ellington, Influenza Division, CDC/NCIRD\n•This topic is presented for information and discussion. Issue:\n•Influenza vaccine effectiveness (VE) varies and is assessed annually through several \nCDC platforms focusing on laboratory -confirmed influenza outpatient visits and \nhospitalizations in adult and pediatric populations.\n•Preliminary 2023 -24 season VE estimates were presented at the February 2024 \nACIP meeting.\n5\nAvian Influenza A(H5N1) Update\nUpdates:\n•Highly Pathogenic Avian Influenza A(H5N1 ) Update\n⁻Dr. Tom Shimabukuro; Deputy Director, Influenza Division, CDC/NCIRD\n•This topic is presented for information and discussion. Issue:\n•Influenza A(H5N1) has been detected in U.S. dairy herds in 14 U.S. states\n•27 human cases have been reported during 2024 .\n6https://www.cdc.gov/bird -flu/situation -summary/index.html  \nVaccines for Children (VFC) Vote\nVote:\n•A VFC resolution is proposed to add options for vaccination of 18 -year -olds who are \nsolid organ transplant recipients.\n⁻Dr. Jeanne Santoli, CDC/NCIRDIssue:\n•High -dose inactivated (HD -IIV3) and adjuvanted inactivated (aIIV3) influenza \nvaccines are approved in the United States for ages ≥65 years.\n•An evidence review of HD -IIV3 and aIIV3 for solid organ transplant (SOT) recipients \nages ≥6 months was presented at the June 2024 ACIP meeting.\n•ACIP voted to recommend that HD -IIV3 and aIIV3 are acceptable options for SOT \nrecipients aged 18 through 64 years who are receiving immunosuppressive \nmedication regimens, without a preference over other age -appropriate inactivated \nor recombinant vaccines. \n7\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the \nofficial position of the Centers for Disease Control and Prevention.", "summary": "National Center for Immunization & Respiratory Diseases Influenza Work Group —Introduction Dr. Jamie Loehr (Work Group Chair) Advisory Committee on Immunization Practices October 23, 2024 Influenza Work Group ACIP Members •Jamie Loehr (Chair) •Robert Schechter •Albert Shaw •Keipp Talbot Ex Officio •Timothy Brennan (FDA) •Uzo Chukwuma (IHS) •Michael Ison (NIH) •Cynthia Nolletti (FDA) •Jo Resnick (FDA) •Chris Roberts (NIH)Liaison Representatives and Consultants •Robert Atmar •Kevin Ault •Ed…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-23-24-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/01-influenza-Loehr-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 8}
{"title": "02 influenza Ellington 508", "content": "National Center for Immunization & Respiratory Diseases\n2023 –24 End of Season Influenza Vaccine Effectiveness – United \nStates\nSascha Ellington, PhD, MSPH\nInfluenza Division \nU.S. Centers for Disease Control and Prevention \n2023 –2024 Influenza Season\n•A(H1N1)pdm09 predominant\n•Lower levels of A(H3N2) and \nB/Victoria circulation\n•Peak activity 2023 week 52\n•Vaccines were quadrivalent and \nincluded A(H1N1)pdm09, \nA(H3N2), and B components\nH1N1\nH3N2B\n3CDC Influenza Vaccine Effectiveness Networks\nInvestigating Respiratory Viruses in the Acutely Ill (IVY)\nNew Vaccine Surveillance Network (NVSN)\nUS Flu Vaccine Effectiveness Network (US Flu VE)\nVirtual SARS -CoV-2, Influenza, and Other respiratory viruses Network (VISION)\n\nVISION\nIVYNVSN\n4These networks include all ages across settings\nAgeSettingOutpatient \nclinic\nHospitalizationEmergency \ndepartment/ \nurgent careUS Flu VE\nAdults \n(≥18 years)Children and adolescents\n(6 months – 17 years)Outpatient\nNVSN\n5NVSN: all settings\nAgeSettingOutpatient \nclinic\nHospitalizationEmergency \ndepartment/ \nurgent care\nAdults \n(≥18 years)Children and adolescents\n(6 months – 17 years)Outpatient\nNVSN\n6US Flu VE: Outpatient clinic and ED/UC\nAgeSettingOutpatient \nclinic\nHospitalizationEmergency \ndepartment/ \nurgent careUS Flu VE\nAdults \n(≥18 years)Children and adolescents\n(6 months – 17 years)Outpatient\nNVSN\n7VISION: ED/UC & hospitalization\nAgeSettingOutpatient \nclinic\nHospitalizationEmergency \ndepartment/ \nurgent careUS Flu VE\nAdults \n(≥18 years)Children and adolescents\n(6 months – 17 years)VISIONOutpatient\nIVY\n8IVY: hospitalization\nAgeSettingOutpatient \nclinic\nHospitalizationEmergency \ndepartment/ \nurgent care\nAdults \n(≥18 years)Children and adolescents\n(6 months – 17 years)Outpatient\nIVY\n9US Flu VE: Outpatient clinic and ED/UC\nAgeSettingOutpatient \nclinic\nHospitalizationEmergency \ndepartment/ \nurgent care\nAdults \n(≥18 years)Children and adolescents\n(6 months – 17 years)US Flu VE Outpatient\nIVY\n10VISION: ED/UC & hospitalization\nAgeSettingOutpatient \nclinic\nHospitalizationEmergency \ndepartment/ \nurgent care\nAdults \n(≥18 years)Children and adolescents\n(6 months – 17 years)US Flu VE\nVISIONOutpatient\nVISION\nIVYNVSN\n11These networks include all ages across settings\nAgeSettingOutpatient \nclinic\nHospitalizationEmergency \ndepartment/ \nurgent careUS Flu VE\nAdults \n(≥18 years)Children and adolescents\n(6 months – 17 years)Outpatient\n12CDC influenza VE networks include patients from 23 states\n13\n?\n142023 –2024 Influenza VE Methods\nEnrollees: Have acute respiratory illness and present for medical care\nDates of enrollment: Fall 2023 –April/May 2024\nDesign: Test-negative design\n›Comparing vaccination odds among case patients with influenza confirmed by \nmolecular assay versus control patients testing negative for influenza and SARS -CoV-2\n›Vaccination status: receipt of any 2023 –24 seasonal flu vaccine according to medical \nrecords, immunization registries, claims data, and/or self -report\n152023 –2024 Influenza VE Methods\nAnalysis : VE = (1 – adjusted OR) x 100%\n›Adjusted for geographic region, age, calendar time of illness\n•IVY , US Flu VE, and VISION also adjusted for sex and race and ethnicity\n•US Flu VE also adjusted for days between illness onset and enrollment and self -reported \ngeneral health status\nVE among children and adolescents aged 6 months – 17 years\n17Pediatric VE against any influenza\nFebruary 2024\n\n18Pediatric VE against any influenza\nFebruary 2024\n19Pediatric VE against influenza A\nFebruary 2024\n\n20Pediatric VE against influenza A\nFebruary 2024\n\n21Pediatric VE against influenza B\nFebruary 2024\n\n22Pediatric VE against influenza B\nFebruary 2024\nVE among adults ages 18 –49 years\n24Adult (aged 18 –49 years) VE against any influenza\n\n25Adult (aged 18 –49 years) against VE influenza A\n\n26Adult (aged 18 –49 years) VE against influenza B\n\nVE among adults aged 50 –64 years\n28Adult (aged 50 –64 years) VE against any influenza\nFebruary 2024, 18–64 years combined\n\n29Adult (aged 50 –64 years) VE against any influenza\nFebruary 2024, 18–64 years combined\n\n30Adult (aged 50 –64 years) VE against influenza A\nFebruary 2024, 18–64 years combined\n\n31Adult (aged 50 –64 years) VE against influenza A\nFebruary 2024, 18–64 years combined\n\n32Adult (aged 50 –64 years) VE against influenza B\nFebruary 2024, 18–64 years combined\n\n33Adult (aged 50 –64 years) VE against influenza B\nFebruary 2024, 18–64 years combined\n\nVE among adults aged ≥65 years\n35Adult (aged ≥65) VE against any influenza\nFebruary 2024\n\n36Adult (aged ≥65) VE against any influenza\nFebruary 2024\n\n37Adult (aged ≥65) VE against influenza A\nFebruary 2024\n\n38Adult (aged ≥65) VE against influenza A\nFebruary 2024\n39Adult (aged ≥65) VE against influenza B\nFebruary 2024\n\n40Adult (aged ≥65) VE against influenza B\nFebruary 2024\nVE by A subtype\n42VE against influenza A(H1N1)pdm09\n\nVE against influenza A(H3N2)\n43\n\nDiscussion\n45Summary of four CDC influenza VE networks\nVaccination with a 2023 –2024 influenza vaccine reduced the risk  of medically \nattended influenza outpatient visits and hospitalizations  among children, \nadolescents, adults, and the elderly .\nResults were consistent across 4 networks in 23 states.\nPreliminary end-of-season  estimates are similar to interim estimates from \nFebruary.\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the \nofficial position of the Centers for Disease Control and Prevention.\nWe’d like to thank our many collaborators from CDC, IVY , NVSN, US Flu VE, and VISIONThank you", "summary": "National Center for Immunization & Respiratory Diseases 2023 –24 End of Season Influenza Vaccine Effectiveness – United  States Sascha Ellington, PhD, MSPH Influenza Division  U.S. Centers for Disease Control and Prevention  2023 –2024 Influenza Season •A(H1N1)pdm09 predominant •Lower levels of A(H3N2) and  B/Victoria circulation •Peak activity 2023 week 52 •Vaccines were quadrivalent and  included A(H1N1)pdm09,  A(H3N2), and B components H1N1 H3N2B 3CDC Influenza Vaccine Effectiveness…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-23-24-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/02-influenza-Ellington-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 46}
{"title": "06 RSV Adult Melgar 508", "content": "RSV Vaccination in Adults:\nWork Group Interpretations\nMichael Melgar, MD\nAmadea Britton, MD, SMAdvisory Committee on Immunization PracticesOctober 24, 2024National Center for Immunization and Respiratory Diseases\n2•Summarize Work Group interpretations of:\n-\n-\n-Current RSV vaccine safety surveillance data and the balance of estimated benefits and risks \nassociated with protein subunit* RSV vaccination in adults ages 60 years and older\nCoadministration of RSV vaccines with other adult vaccines\nClinical trial evidence on protein subunit RSV vaccination* in immunocompromised adults\n•Policy considerations for the adult RSV vaccine programOverview\n*GSK’s Arexvy  and Pfizer’s Abrysvo  are protein subunit RSV vaccines. Moderna’s mResvia  is an mRNA RSV vaccine, not a protein \nsubunit vaccine. \nWork Group interpretation of updated RSV vaccine safety \ndata and the balance of benefits and risks of protein subunit RSV vaccination in adults 60 years and older\n4•A small number of GBS cases were observed in clinical trials within 42 days after protein subunit \nRSV vaccination (GSK Arexvy , Pfizer Abrysvo ). Due to the small number of cases, it was unclear \nwhether they represented a genuine association between RSV vaccination and GBS.\n•Post -licensure data from 2023 –2024 from the Vaccine Adverse Event Reporting System (VAERS)1, \nthe Vaccine Safety Datalink (VSD)2, and from the partnership between the Food and Drug \nAdministration (FDA) and the Centers for Medicare and Medicaid Services (CMS)3,4 suggested, but \ncould not confirm, an elevated risk of GBS after protein subunit RSV vaccination.\n•The current older adult RSV vaccine recommendation is intended to focus the vaccination program on older adults in whom the benefits of vaccination most clearly outweigh the potential risks (all adults aged ≥75 years, adults aged 60 –74 years at increased risk of severe RSV disease).\n•To date, there have been no cases of GBS within 42 days after Moderna mResvia  vaccination in \nclinical trials; post-licensure safety surveillance for this vaccine began in June 2024 after licensure and data are not yet available.RSV vaccine safety recap as of June 2024 :\nGuillain -Barré syndrome (GBS)\n1. https://www.cdc.gov/acip/downloads/slides -2024- 02-28-29/05- RSV- Adults -Shimabukuro -508.pdf  \n2. https://www.cdc.gov/acip/downloads/slides -2024- 06-26-28/05- RSV- Adult -Donahue -508.pdf  \n3. https://www.cdc.gov/acip/downloads/slides -2024- 02-28-29/06- RSV- Adults -Lloyd --508.pdf  \n4. https://www.cdc.gov/acip/downloads/slides -2024- 06-26-28/06- RSV- Adult -Lloyd -508.pdf  \n5As of June 2024:\n•~1.3 million protein subunit RSV vaccine doses, \n2\n8 GBS cases identified through diagnostic codes\n•Elevated incidence rate ratio of GBS following both GSK\n Arexvy  and Pfizer Abrysvo  vaccination, but \nestimates were not statistically significant\n•Data suggested difference in attributable risk by pr\noduct2\n-GSK A rexvy : 3 excess cases per 1 million doses (95% CI: -3, 10)\n-Pfizer A brysvo : 16 excess cases per 1 million doses (95% CI: 3, 29)\n \n•No data available regarding concomitant v\naccinationsUpdate October 2024:\n•~3.2 million protein subunit RSV vaccine doses, 9\n5 GBS cases identified through diagnostic codes \n(24 excluded through medical record review1)\n•Elevated incidence rate ratio of GBS following both v\naccines; results reached statistical significance for \nGSK Arexvy , but not for Pfizer Abrysvo, which had \nfewer doses administered\n•Attributable GBS risk similar for both products2\n-GSK A rexvy : 7 excess cases per 1 million doses (95% CI: 2, 11)\n-Pfizer A brysvo : 9 excess cases per 1 million doses (95% CI: 0, 18)\n•30–50% of doses were concomitantly administered \nwith another vaccine; no evidence that concomitant vaccination explains the increase in GBS rate after protein subunit RSV vaccination\n1.Brighton Collaboration (BC) case definition for GBS was applied, requiring Level 1 –3  certainty: https://brightoncollaboration.org/guillain -barre -and- miller -fisher -syndromes -2/. Of the \n95 initially identified cases, 51 were confirmed through medical record review, 24 were excluded (BC Level 4 –5), and 20 did not have medical record available for review. \n2.Residual confounding is possible, and the analysis was not designed to compare risk between the two vaccines. Baseline risk o f GBS ma y impact estimated attributable risk.What have we learned about GBS risk from the FDA-CMS self -controlled \ncase series analysis since June 2024?\n6The Work Group has previously  reviewed examples from other licensed and \nrecommended vaccines of benefit -risk considerations in practice.\n• Seasonal influenza vaccine: routine annual influenza vaccination is recommended for all persons aged ≥6 \nmonths who do not have contraindications. Adults aged ≥65 years should preferentially receive high -dose, \nrecombinant, or adjuvanted influenza vaccines.1\n–The data on the association between GBS and seasonal influenza vaccination are variable and \ninconsistent across influenza seasons. If there is an increased risk of GBS following influenza vaccination it is small, on the order of 1–2 additional cases per million doses of influenza vaccine \nadministered. Studies also suggest that it is more likely that a person will get GBS after getting influenza disease than after influenza vaccination.\n2\n1. Grohskopf LA, et al. Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices — United States, 2023 –24 Influenza Season. \nMMWR Recomm  Rep 2023;72(No. RR -2):1 –25. http://dx.doi.org/10.15585/mmwr.rr7202a1  \n2. Vellozzi  C, Iqbal S, and Broder K. Guillain- Barré Syndrome, Influenza, and Influenza Vaccination: The Epidemiologic Evidence, Clinical Infectious Diseases , Volume 58, Issue 8, 15 April 2014, Pages 1149 –\n1155, https://doi.org/10.1093/cid/ciu005 .\n7\n–\nRecombinant zoster vaccine : CDC recommends two doses of recombinant zoster vaccine (RZV, Shingrix) 2–6 \nmonths apart for adults aged ≥50 years and for adults aged ≥19 years who are or will be \nimmunocompromised, for prevention of herpes zoster (shingles) and related complications.3,4\n–3–6 additional cases of GBS projected per million RZV vaccinated .5\n–Risk-benefit analysis incorporated available data on risk of GBS following zoster disease and vaccination with RZV\n3. Dooling KL, et al. Recommendations of the Advisory Committee on Immunization Practices for Use of Herpes Zoster Vaccines. MMW R Morb  Mortal Wkly  Rep 2018;67:103– 108. http://dx.doi.org/10.15585/mmwr.mm6703a5  \n4. Anderson TC, et al. Use of Recombinant Zoster Vaccine in Immunocompromised Adults Aged ≥19 Years: Recommendations of the Advi sory Committee on Immunization Practices —  United States, 2022. MMWR Morb  Mortal \nWkly  Rep 2022;71:80 –84. http://dx.doi.org/10.15585/mmwr.mm7103a2  \n5. Janusz CB, et al. Projected risks and health benefits of vaccination against herpes zoster and related complications in US ad ults. Hum Vaccin  Immunother. 2022 Nov 30;18(5):2060668. \nhttps://doi.org/10.1080/21645515.2022.2060668The Work Group also reviewed examples from other licensed and recommended \nvaccines of benefit -risk considerations in practice.\n8Available data suggest that risk is comparable to, and potentially greater than, that of other \nc\nurrently licensed and recommended adult vaccines.\nNo evidence of a difference in risk between protein subunit vaccines1 (GSK, Pfizer).\nThe Work Group emphasized that risk of GBS associated with protein subunit RSV vaccines1 \nshould be considered in the context of the public health benefits of RSV vaccination.\nIn June 2024, ACIP reviewed results of a mathematical modeling analysis comparing the n\numbers of RSV- associated hospitalizations, intensive care unit (ICU) admissions, and deaths \navertable per 1 million persons vaccinated vs. the numbers of potential vaccine- attributable \nGBS cases.2\nThis analysis has been updated to account for the most up to date information on protein s\nubunit RSV vaccine effectiveness, duration of protection, and GBS risk1.The Work Group concluded that available data support existence \nof increased risk of GBS after protein subunit RSV vaccination1\n1.GSK’s A rexvy  and Pfizer’s Abrysvo  are protein subunit RSV vaccines. Moderna’s mResvia  is an mRNA RSV vaccine, NOT a protein subunit vaccine. To date, Moderna’s \nmResvia  vaccine has NOT been associated with increased risk of Guillain- Barré syndrome. Post -licensure safety surveillance for mResvia  began recently in June 2024.\n2.https://www.cdc.gov/acip/downloads/slides -2024 -06-26-28/09- RSV-Adult- Hutton- 508.pdf\n9Same model presented in June 2024, with the following changes:\n•Updated attributable risk estimates for GBS as presented earlier this morning\n•Updated vaccine effectiveness (VE) assumptions\n-Protein subunit RSV vaccination assumed to confer 36 months of protection \n(\nincreased from 24 months)\n-Inclusion of preliminary first- s eason VE estimates against RSV-associated \nhospitalization from a retrospective cohort study in Medicare beneficiaries aged ≥65 years\n1 in the meta -analyses of first- season VE against hospitalization1–4\n•Base case evaluates protein subunit RSV vaccination generally, rather than \nth\ne GSK and Pfizer vaccines individuallyBenefits and risks of protein subunit RSV vaccination \n(GSK Arexvy , Pfizer Abrysvo ): methods updates\n1. Unpublished results from analysis conducted by the Food and Drug Administration (FDA), Center for Biologics Evaluation and Re se arch (CBER), Office of Biostatistics and Pharmacovigilance (OBPV) in partnership with the Centers \nfor Medicare and Medicaid Services (CMS). Personal communication with CDC.\n2. Surie D, Self WH, Zhu Y, et al. Investigating Respiratory Viruses in the Acutely Ill (IVY) Network. RSV Vaccine Effectiveness  Ag ainst Hospitalization Among US Adults 60 Years and Older. JAMA. 2024 Oct 1;332(13):1105- 1107. \nhttps://pubmed.ncbi.nlm.nih.gov/39230920/  \n3. Payne AB, Watts JA, Mitchell PK, et al. Respiratory syncytial virus (RSV) vaccine effectiveness against RSV- as sociated hospitalisations and emergency department encounters among adults aged 60 years and older in the USA, \nOctober, 2023, to March, 2024: a test -negative design analysis. The Lancet. 2024;404(10462):1547-1559. https://doi.org/10.1016/S0140- 6736(24)01738-0  \n4. Unpublished results from the Veterans Health Administration presented in June 2024: https://www.cdc.gov/acip/downloads/slides -2024- 06-26-28/07-RSV- Adult -Surie -508.pdf  \n10Per 1 Million Persons Vaccinated with Protein Subunit RSV Vaccine :\n1.Range of outcomes avertable was calculated using published 95% confidence intervals (outpatient only) and adjusted 95% confid en ce interval of RSV -associated incidence of the outcome observed in RSV -NET\n2.FDA self - controlled case series analysis, among CMS Medicare beneficiaries ≥65 years with Parts A, B, and D coverage who did not  have a GBS claim in the 365 days before vaccination. Analysis based on \ndiagnoses of GBS in inpatient claims data in risk interval (1 –42 days after RSV vaccination) compared to control interval (43 –90 days after RSV vaccination). GBS cases identified using ICD -10 diagnosis of GBS in \nprimary position of inpatient claims coding with chart verification requiring Brighton Collaboration Level 1 –3 certainty. Estima tes adjusted for outcome-dependent observation time, seasonality, and (when \nchart review could not be performed) the positive predictive value of diagnostic codes in identifying chart -confirmed GBS cases.  Analysis includes patients with RSV vaccinations only through January 28, 2024 \nto allow for 90-day post -vaccination observation and 90% or greater claims data completeness. Claims data through July 13, 2024. \n3.Although CMS data were limited to Medicare beneficiaries aged ≥65 years, results are extrapolated here to include adults aged 60 -64 years.\n4.Credible range spans the lowest lower bound and highest upper bound of attributable risk estimates for the GSK and Pfizer RSV  v accines.Estimated RSV -Associated Outcomes1 Preventable over 3 RSV Seasons  vs. attributable risk of GBS \nestimated from self-controlled case series analysis through FDA -CMS partnership, 42-day risk interval2\n0–184 attributable  cases of GBS790 830 5,600 \n0 1000 2000 3000 4000 5000 6000 7000 8000 9000320 850 3,700 \n0 1000 2000 3000 4000 5000 6000 7000 8000 9000Adults Aged 60–74 Years3 at Increased \nRisk of Severe RSV Disease\n(1,700–6,900)\n(390–1,580)\n(120 –610)Hospitalizations\nICU Admissions\nDeathsAd ults Aged ≥75 Years, \nGeneral Population\n(3,600–8,900)\n(520–1,310)\n(310–1,450)\nCredit: Dr. David Hutton, U. Michigan\n11•No statistical signal for GBS in rapid cycle analysis to date.\n•As was seen in June 20242, there is a numerical imbalance in the number of GBS cases after \nGSK Arexvy  vaccination in adults aged ≥60 years, but the number of cases is small. The \nsystem is currently underpowered to determine whether there is an association with GBS.\n•Similarly2, after medical record review, there is a numerical imbalance in the small number \nof cases of immune thrombocytopenia (ITP) after GSK Arexvy  vaccination without another \nsimultaneous vaccine in adults aged ≥60 years, but due to the small number of cases, the \nsystem is currently underpowered to determine whether there is an association with ITP .\n•Fewer doses of Pfizer Abrysvo  were administered in VSD, and no conclusions can be drawn \nfrom this system regarding the safety of this vaccine at this time.The Work Group also reviewed updated safety data from the \nVaccine Safety Datalink (VSD) on protein subunit RSV vaccines1.\n1.GSK’s Arexvy  and Pfizer’s Abrysvo  are protein subunit RSV vaccines. Moderna’s mResvia  is an mRNA RSV vaccine, NOT a protein subunit vaccine. To date, Moderna’s \nmResvia  vaccine has NOT been associated with increased risk of Guillain- Barré syndrome. Post -licensure safety surveillance for mResvia  began recently in June 2024.\n2.https://www.cdc.gov/acip/downloads/slides -2024 -06-26-28/05 -RSV -Adult -Donahue-508.pdf  \nWork Group interpretations on \nco-administration of RSV vaccines \nwith other adult vaccines\n13•Co-administration of RSV vaccines and other recommended adult vaccines, in \nparticular seasonal influenza and COVID- 19 vaccines, is common\n•The Work Group was reassured to see these first- ever data from Pfizer \ndemonstrating that co- administration of protein subunit RSV vaccine, mRNA COVID-\n19 vaccine, and high- dose influenza vaccine was safe and generated a non- inferior \nhumoral immune response \n•The Work Group acknowledged the findings of an inferior RSV neutralizing antibody \nresponse with co- administration of Moderna RSV vaccine and high- dose influenza \nvaccine, but feels clinical significance of this finding is currently unknown\n•These data should also be put in context of a lack of a consistent pattern in combinations of RSV vaccine and other concomitant vaccinations that resulted in inferior immune responsesWork Group interpretations of new co -administration \ndata\n14GSK RSV vaccine Pfizer RSV vaccine Moderna RSV vaccine \nStandard dose \ninfluenza vaccineCoadministration non\n-inferior No data available Coadministration non- inferior\nAdjuvanted \ninfluenza vaccineCoadministration non- inferiority \ncriteria not met\n•RSV titers: non -inferior\n•Influenza titers: H3N2 HAI1titers \ninferior w/ coadministrationCoadministration non-\ninferiorNo data available\nHigh -dose influenza \nvaccineCoadministration non- inferior Coadministration non-\ninferior2Coadministration non- inferiority \ncriteria not met•RSV titers: RSV -A and B \nneutralizing antibody titers \ninferior w/ coadministration \n•Influenza titers: non -inferior\nmRNA COVID -19 \nvaccineNo data availableCoadministration non-\ninferiorCoadministration non- inferiorSummary of RSV coadministration data with influenza and/or COVID -19 mRNA vaccines in \nwhich non -inferiority of humoral immune response was assessed in older adults\n1. HAI: hemagglutination inhibition. Humoral immune response against influenza A/Darwin H3N2 was also assessed post -ho c via microne utralization, which \nresulted in a geometric mean titer (GMT) ratio similar to the HAI GMT ratio, with a slightly narrower confidence interval: 1. 23 (95% CI: 1.06 –1.42). Non -inferiority \ncriteria were not specified for post -hoc analyses. Prespecified non -inferiority criteria for the HAI GMT ratio required that the  95% CI upper bound was <1.50. \n2. When given as 3 -wa y coadministration (high -dose influenza vaccine + COVID -19 vaccine + Pfizer RSV vaccine)\n15•The Work Group notes our limited understanding of clinical significance of \ndecreased antibody titers with RSV vaccine co -administration. \n•Given the considerable benefits of co -administration and the evidence of \nsafety of co -administration, the Work Group continues to feel co -\nadministration is acceptable.1 \n•In addition, the Work Group looks forward to learning more about Moderna’s analysis on immunologic correlates of protection for RSV as peer -\nreviewed methods become available.Work Group interpretations of new co -administration \ndata (continued)\n1.This language is different from CDC’s General Best Practices Guidelines for Immunization, which states that with limited exce ption, \nroutine administration of all age -appropriate doses of vaccines simultaneously is recommended for persons for whom no specific \ncontraindications exist at the time of the visit.\nKroger A, Bahta  L, Long S, Sanchez P . General Best Practice Guidelines for Immunization. Best Practices Guidance of the Advisory Committee on  \nImmunization Practices (ACIP). https://www.cdc.gov/vaccines/hcp/acip -recs/general -recs/index.html . Updated July 22, 2024; accessed October 22, 2024\nWork Group interpretations on use of RSV \nvaccines in adults with immune compromise\n17•During today’s meeting, GSK and Pfizer presented clinical trial data on use of \nt\nheir RSV vaccines in adults aged ≥18 years with immune compromise. \n•These are the first clinical trial results in these populations at high risk of se\nvere RSV disease.\n•Notably, these trials studied the safety of and the immune response to RSV \nv\naccination, but did not estimate efficacy against clinical endpoints. First RSV vaccine trials in immunocompromised \npersons\n18What did we learn from these clinical trials?\nGSK Arexvy\n•Trial included adults aged ≥18 years with renal or lung \nt\nransplant\n•One month after a single dose of A rexvy , these \nparticipants had lower RSV neutralizing antibody titers, compared with immunocompetent adults aged ≥50 years\n•After a second dose of A\n rexvy  one month after the \nfirst, RSV neutralizing antibody titers increased and were similar to those in immunocompetent adults aged ≥50 years at 2 months post -vaccination\n•Measures of cellular immunity after Arexvy  \nv\naccination were similar between \nimmunocompromised participants and immunocompetent participants\n•No specific safety concerns were identified in either clinical trial, though one participant in each trial experienced r\nenal transplant rejection after RSV vaccination (judged by investigator to be unrelated to vaccination)\n19What did we learn from these clinical trials?\nGSK Arexvy\n•Trial included adults aged ≥18 years with renal or lung \nt\nransplant \n•One month after a single dose of A rexvy , these \nparticipants had lower RSV neutralizing antibody titers, compared with immunocompetent adults aged ≥50 years\n•After a second dose of A\n rexvy  one month after the \nfirst, RSV neutralizing antibody titers increased and were similar to those in immunocompetent adults aged ≥50 years at 2 months post -vaccination\n•Measures of cellular immunity after Arexvy  \nv\naccination were similar between \nimmunocompromised participants and immunocompetent participantsPfizer Abrysvo\n•Trial included adults aged ≥18 years with autoimmune d\nisorders on immunomodulator therapy, solid organ \ntransplant, end- stage renal disease on dialysis, or non-\nsmall cell lung cancer on therapy\n•One month after a single dose of Ab rysvo , these \nparticipants had similar RSV neutralizing antibody titers, compared with immunocompetent adults aged ≥60 years from Pfizer’s main phase 3 trial\n•The neutralizing antibody response in participants w\nith autoimmune disorders on immunomodulator \ntherapy and solid organ transplant appeared lower than in adults with end- stage renal disease\n•A second dose of Ab\n rysvo  one month after the first did \nnot appreciably increase neutralizing antibody titers \n•No specific safety concerns were identified in either clinical trial, though one participant in each trial experienced r\nenal transplant rejection after RSV vaccination (judged by investigator to be unrelated to vaccination)\n20•The Work Group was encouraged to see clinical trial data in this population \nbut would have preferred to see data among adults with the most severe \nforms of immune compromise, who are at highest risk of severe RSV disease \n(e.g., hematopoietic stem cell transplant, recent lung transplant).\n•The Work Group also felt that Pfizer’s inclusion of adults with end -stage \nrenal disease on dialysis used too broad a definition of immune compromise.\n•The Work Group expressed uncertainty in whether neutralizing antibody \ntiters will correspond to similar clinical efficacy observed in \nimmunocompetent older adults.\n•Absent clinical efficacy data, the Work Group expressed uncertainty in whether 2 doses of GSK’s Arexvy  would be required to result in adequate \nprotection against severe RSV disease in solid organ transplant recipients.Work Group interpretations \nPolicy considerations\n22•Adults aged ≥75 years should receive a single dose of RSV vaccine\n•Adults aged 60– 74 years who are at increased risk of severe RSV disease \nshould receive a single dose of RSV vaccine\n•While uncertainty remains regarding the magnitude of GBS risk associated \nwith protein subunit RSV vaccination*, the Work Group believes that the \nbenefits of RSV vaccination outweigh risks among the populations for whom \nRSV vaccination is currently recommended.The Work Group affirms that the current older adult \nRSV vaccine recommendations are appropriate.\n*GSK’s Arexvy  and Pfizer’s Abrysvo  are protein subunit RSV vaccines. Moderna’s mResvia  is an mRNA RSV vaccine, NOT a protein subunit vaccine. To date, Moderna’s \nmResvia  vaccine has NOT been associated with increased risk of Guillain -Barré syndrome. Post -licensure safety surveillance for mResvia  began recently in June 2024.\n23•The Work Group recognizes several important factors: \n-While risk of severe RSV disease increases with age, adults aged <60 years with \ncertain chronic medical conditions have an elevated risk of severe RSV disease: some may have risk comparable to that in older adults \n-Adults from certain racial and ethnic groups may be at increased risk of these conditions at younger ages, compared with White adults\n-Conditions that elevate the risk of severe RSV disease may differ by age group; conditions that place adults aged 60– 74 years at increased risk of severe RSV may \nnot confer the same degree of absolute risk in adults aged 18– 59 years\n-Developing RSV vaccine policy in adults <60 years will require careful consideration of the balance of public health benefits and risks in this populationThe Work Group continues to evaluate recommendations for the use \nof RSV vaccines in adults aged <60 years, acknowledging there are \nnow two FDA-approved products for RSV prevention in this age group\n24•As was discussed at the June 2024 ACIP meeting, the Work Group felt additional data \non \nthe potential risk of GBS associated with RSV vaccination were essential prior to \nconsidering RSV vaccine recommendations in adults aged <60 years\n•Today we have seen updated results increasing certainty that protein subunit RSV v\naccination* is associated with GBS risk, though uncertainty remains regarding the \nmagnitude of risk \n•The Work Group will use these data to continue evaluating risks and benefits, including i\nn which groups among adults younger than 60 years the estimated benefits outweigh \nthe risks\n*GSK’s Arexvy  and Pfizer’s Abrysvo  are protein subunit RSV vaccines. Moderna’s mResvia  is an mRNA RSV vaccine, NOT a protein subunit vaccine. To date, Moderna’s \nmResvia  vaccine has NOT been associated with increased risk of Guillain- Barré syndrome. Post -licensure safety surveillance for mResvia  began recently in June 2024.The Work Group continues to evaluate recommendations for the use \nof RSV vaccines in adults aged <60 years, acknowledging there are \nnow two FDA-approved products for RSV prevention in this age group\n25•Regarding immunocompromised adults, the Work Group recognizes this is a \nheterogeneous group who are not all at the same risk of severe RSV disease\n•While the data presented today covered a subset of those with immune compromise, \nthe Work Group does not feel they substantially increase certainty that those with the \nmost severe forms of immune compromise will benefit from vaccination (e.g., hematopoietic stem cell transplant recipients)\n•Therefore, the Work Group did not feel that the data presented today motivated an immediate policy expansion for this group in younger adults, particularly while the FDA-CMS analysis on GBS risk is still ongoingThe Work Group continues to evaluate recommendations for the use \nof RSV vaccines in adults aged <60 years, acknowledging there are \nnow two FDA-approved products for RSV prevention in this age group\n26•At least one complete season of safety surveillance data. \n-Depending on certainty of findings, additional data may be needed. \n•Immunobridging data in adults with immune compromise. \n•Data on duration of protection and immune response after re -vaccination.\n-The Work Group expressed concern that to date there are no data showing re- vaccination will restore \nprotection if efficacy wanes over time.\n-While restoration of protection with re -vaccination is likely, efficacy in GSK’s pivotal phase III trial did not \nimprove after re -vaccination at a 12 -month interval.1\n-GSK immunogenicity data at 12 - and 24 -month re -vaccination intervals have shown a weaker humoral \nimmune response, compared with the response after dose 1.2 Pfizer immunogenicity data at a 12 -month re -\nvaccination interval has also shown a weaker humoral immune response, compared with the response after \ndose 1.3At the June 2024 ACIP meeting the Adult RSV Work Group indicated they \nwould like to see the following data before moving to vote on an RSV \nvaccine recommendation for adults aged <60 years:\n1.Ison MG, Papi  A, Athan  E et al. Efficacy and Safety of Respiratory Syncytial Virus (RSV) Prefusion F Protein Vaccine (RSVPreF3 OA) in Older Adults Over 2 RSV  Seasons. Clinical Infectious Diseases. Vol 78(6):1732 -1744. Jan 2024. \n2.Gerber, S. Arexvy  (Adjuvanted RSVPreF3) 2 -Year Update. Presented at the Advisory Committee on Immunization Practices meeting, Atlanta, GA; June 26, 2024. https://www.cdc.gov/acip/down loads/slides -2024 -06-26-28/03- RSV-Adult -Gerber -508.pdf.\n3. Walsh EE et al. Respiratory Syncytial Virus Prefusion F Vaccination: Antibody Persistence and Revaccination, The Journal of Inf ectious Diseases, The Journal of Infectious Diseases, Vol. 230( 4) Pages e905–e916. Oct. 2024. \nhttps://academic.oup.com/jid/advance -article/doi/10.1093/infdis/jiae185/7644684 .\n27•Final results from the FDA - CMS analysis from the first season of RSV \nvaccination in Medicare beneficiaries\n-The Work Group continues to feel that depending on certainty of findings, additional \nda\nta may be needed, and will continue to evaluate other sources of safety data\n•Pending certainty in safety findings, data demonstrating vaccine efficacy or \ne\nffectiveness against clinical endpoints in the most severely \nimmunocompromised adults\n-While the Work Group appreciates new immunogenicity data, they do not feel these \nda\nta are sufficient to support age expansion without final FDA -CMS results on GBS risk\n•Immunogenicity data after revaccination with longer time intervals following \nin\nitial vaccination\n-Additional data on longer re -v accination intervals is expected from ongoing \nmanufacturer clinical trials\n Today  the Work Group continues to feel additional data are necessary before \nmoving to vote on an RSV vaccine recommendation for adults aged <60 years:\nFor more information, contact CDC\n1-800- CDC- INFO (232- 4636)\nTTY:  1 -888- 232- 6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.\n\n29• Observation Period : August 6, 2023 to March 2, 2024  \no Restricted follow up to high -circulation periods after October 1, 2023 with RSV circulation ≥8 cases per 100k beneficiaries\n• Outcome : RSV -associated hospitalization identified through International Classification of Diseases, 10th revision, Clinical Modification diagnostic codes\n• Covariates : \no Time-fixed covariates in the 365 days prior to index:  \nDemographic  characteristics (e.g., age, sex, race), socioeconomic status (dual eligibility in Medicare/Medicaid, area deprivation index),  and health conditions (e.g., frailty \nscore, general medical conditions, immunocompromised status).\nImmunocompromised status is determined as a binary covariate based on the presence of immunocompromising diagnoses or treatment\no Time-varying covariates: Census tract -level infection rates\n• Statistical Analysis : Marginal Structural Model with Time-Varying Cohorts  \no Inverse probability of treatment weighting \no Doubly robust Poisson model with intercepts for the time intervals (weeks) Food and Drug Administration (FDA) RSV vaccine effectiveness analysis among \nCommunity -dwelling Medicare Fee -For-Service (FFS) beneficiaries aged 65 years and \nolder without dialysis, preliminary results\nNumber of Eligible \nBeneficiariesMedian Age (IQR)Number of\nRSV-associated\nHospitalizationsPerson-Weeks \n(100,000)Median Follow -up \nDays Contributed to \nCategoryAdjusted VE against\nRSV-associated Hospitalization \n(95% CI)\nUnvaccinated 10,938,075 74 (70, 79) 12,569 2,220.7 126 Reference\nEither Product 2,887,152 74 (70, 79) 486 401.8 101 81.8% (80.0%, 83.4%)\nGSK RSV Vaccine 1,975,732 74 (70, 79) 352 273.1 100 80.0% (77.8%, 82.1%)\nPfizer RSV Vaccine 911,420 75 (70, 80) 134 128.6 104 84.9% (82.1%, 87.3%)Back up slide not shown at meeting", "summary": "RSV Vaccination in Adults: Work Group Interpretations Michael Melgar, MD Amadea Britton, MD, SMAdvisory Committee on Immunization PracticesOctober 24, 2024National Center for Immunization and Respiratory Diseases 2•Summarize Work Group interpretations of: - - -Current RSV vaccine safety surveillance data and the balance of estimated benefits and risks  associated with protein subunit* RSV vaccination in adults ages 60 years and older Coadministration of RSV vaccines with other adult vaccines…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-23-24-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/06-RSV-Adult-Melgar-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 29}
{"title": "01 IZ Schedules Cineas 508", "content": "Recommendations from the Combined Immunization \nSchedule Work Group for the 2025 Immunization \nSchedules for Children/Adolescents and Adults \nSybil Cineas, MD, FAAP , FACP (ACIP Combined Immunization WG Chair)\nNanda Issa, MD ( CDC Co -Lead )\nPatricia Wodi, MD (CDC acting Co -Lead)\nACIP Meeting\nOctober 24, 2024National Center for Immunization and Respiratory Diseases\n\nThe Combined Immunization Schedules WG:\n•Updates the immunization schedules annually\n-Child and adolescent schedule \n(for ages 18 years or younger) \n-Adult schedule                                                   \n(for ages 19 years or older)\n•Harmonizes the child/adolescent and adult \nschedulesCombined Immunization Schedules Work Group\nhttps://www.cdc.gov/vaccines/hcp/imz -schedules/index.html\n2\n•The immunization schedules are \nprimarily designed to be a tool for \nhealthcare providers to ensure \nindividuals get all the vaccines \nthey need when they need them. Combined Immunization Schedules Work Group\nhttps://www.cdc.gov/vaccines/hcp/imz -schedules/index.html\n3\n•The immunization schedules \nreflect existing ACIP \nrecommendations approved by \nthe CDC director.\n-New vaccination policies are not \nestablished in the immunization \nschedules.Combined Immunization Schedules Work Group\nhttps://www.cdc.gov/vaccines/hcp/imz -schedules/index.html\n4\n•ACIP approval of the proposed schedules is necessary prior to publicationReason Topic is Being Presented to ACIP\nChild/Adolescent Schedule \nonlyBoth Schedules Adult Schedule only\n5\nCombined Immunization Schedules Work Group\nACIP Members\nSybil Cineas (ACIP WG Chair)\nCharlotte Moser\nLiaison Representatives\nJohn Epling (AAFP)                         Mary -Margaret Fill (CSTE)\nSarah Coles (AAFP)   Yekatherine  Rasmussen (ACP)\nRhoda Sperling (ACOG)  William Schaffner (NFID)\nHolly Fontenot (SAHM)   Robert Hopkins (NFID)\nAmy Middleman (SAHM)                         Ken Schmader (AGS)\nSandra Fryhofer (AMA)                             Dana DeShon (NAPNAP)\nSarah McQueen (AAPA)                        Preeti Mehrotra (SHEA)\nMarie -Michele Leger (AAPA) Pia Pannaraj (AAP)\nCaitlin Newhouse (AIM)                            Kelly Goode ( APhA )Ex Officios\nDavid Kim (OASH)\nSusan Farrall (OASH)\nJane Kim (DVA)\nUzo Chukwuma (IHS)\nBrittany Rizek (HRSA)\nConsultants\nCarolyn Bridges\nDiane Peterson\nHank Bernstein\nKaren Ketner\nKathleen Harriman\nKevin Ault \nLitjen Tan\nPeter Szilagyi\nSusan LettCDC Co -Leads\nA. Patricia Wodi\nNanda Issa\n6\n•ACIP Combined Immunization Work Group — CDC Contributors:Combined Immunization Schedules Work Group\n–Akiko Wilson\n–Agam Rao\n–Andrew Kroger\n–Amadea Britton \n–David Sugerman \n–Dan Filardo\n–Daniella Moulia\n–Donna Williams\n–Emily Cartwright\n–Erin Conners\n–Femi Adeleke\n–Hilda Razzaghi\n–Holly Hill\n–Jacqueline Tate\n–Janell King\n–Jefferson Jones –Jennifer Collins\n–JoEllen Wolicki\n–Joseph Alcober\n–Joshua Wong \n–Katherine Fleming -Dutra\n–Lakshmi Panagiotakopoulos\n–Lauren Roper\n–Lauri Markowitz\n–Lisa Grohskopf\n–Liz Velazquez\n–Mary Chamberland\n–Megan Wallace\n–Megan Hofmeister\n–Michael Melgar \n–Michelle Hughes\n–Min Kim–Miwako Kobayashi\n–Mona Marin\n–Mona Doshani\n–Paul Gastanaduy\n–Sarah Kidd\n–Sarah Schillie\n–Susan Goldstein\n–Suzanne Johnson -DeLeon\n–Tara Anderson\n7\n•The use of vaccine trade names is for identification purposes only and \ndoes not imply endorsement by the Centers for Disease Control and \nPrevention.\n•The 2025 immunization schedules presented in the following slides are \ndrafts and are therefore subject to change based on ACIP’s discussion and \nvote.Disclaimer\n8\n•Harmonization between the child/adolescent and adult schedules\n•Edits to all tables\n•Content changes of the notes\n•Content changes to the appendix listing contraindications and precautions\n•Discussion and VoteOutline\n9", "summary": "Recommendations from the Combined Immunization  Schedule Work Group for the 2025 Immunization  Schedules for Children/Adolescents and Adults  Sybil Cineas, MD, FAAP , FACP (ACIP Combined Immunization WG Chair) Nanda Issa, MD ( CDC Co -Lead ) Patricia Wodi, MD (CDC acting Co -Lead) ACIP Meeting October 24, 2024National Center for Immunization and Respiratory Diseases  The Combined Immunization Schedules WG: •Updates the immunization schedules annually -Child and adolescent schedule  (for ages…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-23-24-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/01-IZ-Schedules-Cineas-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 9}
{"title": "02 IZ Schedules Issa 508", "content": "Recommendations from the Combined Immunization \nSchedule Work Group for the 2025 Immunization \nSchedules for Children/Adolescents and Adults \nSybil Cineas, MD, FAAP , FACP (ACIP Combined Immunization WG Chair)\nNanda Issa, MD (CDC Co -Lead )\nPatricia Wodi, MD (CDC acting Co -Lead)\nACIP Meeting\nOctober 24, 2024National Center for Immunization and Respiratory Diseases\n\nDr. Nanda Issa2025 Update to Child and Adolescent Immunization Schedule\nAge 18 years or younger\nHow to Use the Immunization Schedule\nSections\n•Cover Page\n•Table 1: Age -based\n•Table 2: Catch -up\n•Table 3: Medical indication\n•Vaccination notes\n•Appendix: contraindications \nand precautions\n•Addendum: updates after \nschedule is published\nChild and Adolescent Immunization Schedule by Age (Addendum updated June 27, 2024) | Vaccines & Immunizations | CDC\n 3\nProposed Update to the 2025 Child/Adolescent Immunization \nSchedule \nChanges to Tables\n•Cover Page\n•Table 1\n•Table 2\n•Table 3Changes to Vaccination Notes\n•COVID -19\n•DTaP\n•Hib\n•Influenza\n•MMR\n•MenB  \n•Pneumococcal\n•RSV monoclonal antibody\n•RSV vaccineChanges to Appendix\n•MMR/MMRV\n•Varicella\n1. Use of COVID -19 Vaccines for Persons Aged ≥6 Months: Recommendations of the Advisory Committee on Immunization Practices — Unite d States, 2024 –2025 | MMWR (cdc.gov)\n2. Use of Haemophilus influenzae Type b –Containing Vaccines Among American Indian and Alaska Native Infants: Updated Recommendation s of the Advisory Committee on Immunization Practices ― United \nStates, 2024 | MMWR (cdc.gov)\n3. Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practic es — United States, 2024 –25 Influenza Season | MMWR (cdc.gov) 4\nCover page\n6\nTable 1\nImmunization schedule by age group\n8\n9\n10\n11\n12\nTable 2\nCatch -up immunization schedule\n14\nTable 3\nImmunization schedule by medical indication\n16\n17\nNotes\nRoutine vaccination\nPersons  NOT  moderately or severely \nimmunocompromised\n• Outlines vaccination series by age \ngroup and COVID -19 vaccination \nhistory.\nSpecial situations\nPersons who ARE \nmoderately or \nseverely \nimmunocompromised\n•Outlines vaccination \nseries by age group \nand COVID -19 \nvaccination history.\n19\n20\n21\n22\n23\nVaxelis  and PedvaxHIB  preferred for \nprimary series in American Indian \nand Alaska native infants.\nGuidance for use of Hib in \nchildren receiving early \ncomponent complement \ninhibitor.\n24\n25\n26\n27\n28\n29\n30\n31\nAppendix\nContraindications and precautions\n33\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention.Thank you!\nQuestions?", "summary": "Recommendations from the Combined Immunization  Schedule Work Group for the 2025 Immunization  Schedules for Children/Adolescents and Adults  Sybil Cineas, MD, FAAP , FACP (ACIP Combined Immunization WG Chair) Nanda Issa, MD (CDC Co -Lead ) Patricia Wodi, MD (CDC acting Co -Lead) ACIP Meeting October 24, 2024National Center for Immunization and Respiratory Diseases  Dr. Nanda Issa2025 Update to Child and Adolescent Immunization Schedule Age 18 years or younger How to Use the Immunization…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-23-24-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/02-IZ-Schedules-Issa-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 34}
{"title": "03 IZ Schedules Wodi 508", "content": "Recommendations from the Combined Immunization \nSchedule Work Group for the 2025 Immunization \nSchedules for Children/Adolescents and Adults \nSybil Cineas, MD, FAAP , FACP (ACIP Combined Immunization WG Chair)\nNanda Issa, MD (CDC Co -Lead)\nPatricia Wodi, MD (CDC acting Co -Lead)\nACIP Meeting\nOctober 24, 2024National Center for Immunization and Respiratory Diseases\n\nDr. Patricia Wodi 2025 Update to Adult Immunization Schedule\nAge 19 years or older\nHow to Use the Immunization Schedule\nSections\n•Cover Page\n•Table 1: Age -based\n•Table 2: Medical indication\n•Vaccination notes\n•Appendix: contraindications \nand precautions\n•Addendum: updates after \nschedule is published\n3\nProposed Updates to the 2025 Adult Immunization Schedule \nChanges to Tables\n•Cover Page\n•Table 1\n•Table 2Changes to Vaccination Notes\n•COVID -19\n•Hepatitis B\n•Influenza\n•Meningococcal \n•Mpox\n•Pneumococcal\n•RSV vaccine\n•TdapChanges to Appendix\n•Pneumococcal\n•Hepatitis B\n1. Use of COVID -19 Vaccines for Persons Aged ≥6 Months: Recommendations of the Advisory Committee on Immunization Practices — Unite d States, 2024 –2025 | MMWR (cdc.gov)\n2. Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practic es — United States, 2024 –25 Influenza Season | MMWR (cdc.gov)\n3. Use of 21 -Valent Pneumococcal Conjugate Vaccine Among U.S. Adults: Recommendations of the Advisory Committee on Immunization Pra ctices — United States, 2024 | MMWR (cdc.gov)\n4. Use of Respiratory Syncytial Virus Vaccines in Adults Aged ≥60 Years: Updated Recommendations of the Advisory Committee on Im mun ization Practices — United States, 2024 | MMWR (cdc.gov)4\nCover page\n6\n7\n8\nTable 1\nImmunization schedule by age group\n10\n11\n12\n13\n14\n15\n16\n17\n18\nTable 2\nImmunization schedule by medical indication\n20\n21\n22\n23\nNotes\nRoutine vaccination\nPersons  NOT  moderately or severely \nimmunocompromised\n• Outlines vaccination series by COVID -19 \nvaccination history.Special situations\nPersons who ARE moderately or \nseverely immunocompromised\n•Outlines vaccination series by \nCOVID -19 vaccination history.\n25\n26\n27\n28\n\n29\n\n30\n\n31\nDelete\n*Note: Heplisav -B and PreHevbrio  are not \nrecommended in pregnancy due to lack of \nsafety data in pregnant persons. \n32\n33\n34\n35\n36\n37\n38\n39\n40\n41\n42\n43\n44\n45\nAppendix\nContraindications and precautions\n47\nDelete\nPregnancy : Heplisav -B and PreHevbrio  \nare not recommended due to lack of \nsafety data in pregnant persons. Use \nother hepatitis B vaccines if HepB  is \nindicated.\n \n48\nFor more information, contact CDC/ATSDR\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov           www.atsdr.cdc.gov \nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention and the Agency for Toxic Substances and Disease Registry.\nThank you!\nQuestions?\nBackup slides\nUse of Hepatitis B vaccine during pregnancy(1)\n•On September 11, 2024, the FDA announced its approval for a labeling change \nfor Heplisav -B stating that there is now safety data for its use among pregnant \npersons.\n•CDC has an update regarding this labeling change in clearance for publication \nin MMWR.\n–Update recommends, Providers can now vaccinate pregnant persons needing HepB  \nvaccination with Engerix -B, Recombivax HB, Twinrix, or Heplisav -B. \n51\nUse of Hepatitis B vaccine during pregnancy(2)\n•Prior to September 2024, neither Heplisav -B nor PreHevbrio  had sufficient safety data \namong pregnant persons to meet FDA requirements for update to their standardized \npackage inserts.\n–8.1 Pregnancy\nRisk Summary\nAll pregnancies have a risk of birth defect, loss, or other adverse outcomes. In the U.S. \ngeneral population, the estimated background risk of major birth defects and miscarriage \nin clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.\nData\nHuman Data: Determination that rates of miscarriage and birth defects are not above \nbackground.\nAnimal Data:  Data from developmental toxicity studies if they exist.\n52\nUse of Hepatitis B vaccine during pregnancy(3)\n•Recommendations for vaccination of pregnant persons is addressed in the 2018 \nMMWR: Prevention of Hepatitis B Virus Infection in the United States: \nRecommendations of the Advisory Committee on Immunization Practices.\n–Guideline lists and describes all vaccines recommended for use in the United States  \nbut makes NO preferential recommendation for use of any particular vaccine.\n53", "summary": "Recommendations from the Combined Immunization  Schedule Work Group for the 2025 Immunization  Schedules for Children/Adolescents and Adults  Sybil Cineas, MD, FAAP , FACP (ACIP Combined Immunization WG Chair) Nanda Issa, MD (CDC Co -Lead) Patricia Wodi, MD (CDC acting Co -Lead) ACIP Meeting October 24, 2024National Center for Immunization and Respiratory Diseases  Dr. Patricia Wodi 2025 Update to Adult Immunization Schedule Age 19 years or older How to Use the Immunization Schedule Sections…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-23-24-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/03-IZ-Schedules-Wodi-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 53}
{"title": "01 hpv Brooks 508", "content": "Introduction to the HPV Vaccines Work Group\nOliver Brooks, MD\nChair, HPV Vaccines Work Group\nAdvisory Committee on Immunization Practices\nOctober 24, 2024\nNational Center for Immunization & Respiratory Diseases\n•HPV Vaccines Work Group re -formation announced at June 2024 \nACIP meeting\n•An HPV Vaccines Work Group met previously for many years, but \nhad been inactive since 2019\n•3 meetings since July 2024Background\n2\n•Routine vaccination\n-Age 11 or 12 years \n-Can be started at age 9 years \n•Catch -up vaccination \n-Through age 26 years\n•Shared clinical decision -making \n-Age 27 –45 yearsCurrent HPV vaccination recommendations, \nUnited States\nRecommendations of the Centers for Disease Control and Prevention and the Advisory Committee on Immunization Practices \nhttps://www.cdc.gov/vaccines/hcp/acip -recs/vacc -specific/hpv.html  Number of doses\n2 doses  (0, 6 -12 months) \nif starting series before 15th birthday\n3 doses  (0,1-2, 6 months) \nif starting series on or after 15th birthday or if \nimmunocompromising condition\n3\n•Number of doses in the recommended HPV vaccination series\n-Accumulating evidence on efficacy of HPV vaccination with fewer doses\n-In 2022, the World Health Organization recommended a two -dose schedule for \npersons aged 9 years or older and, a s an off -label option, a single -dose schedule \ncan be used for those aged 9 –20 years\n-Work Group is reviewing data to inform policy for:\n•two doses for persons aged 15 years and older\n•one dose for persons aged 9 years and olderWork Group Terms of Reference\n4\n•Wording of the age for routine HPV vaccination\n-Some stakeholders interested in starting vaccination at age 9 years\n-Current ACIP recommendations are consistent with vaccination at age 9 years\n-Work Group is considering m odification of wording to “ HPV vaccination is routinely \nrecommended at age 9 to 12 years”  to allow more flexibility Work Group Terms of Reference\n5\n•Reviewed background data on the two issues being considered\n•Number of doses in the recommended HPV vaccination series:\n-Started GRADE process\n-Planning full Evidence to Recommendations ( EtR) framework and ACIP vote at \nfuture meeting\n•Wording of the age for routine HPV vaccination:\n-Reviewed related literature\n-Not using GRADE\n-Planning modified EtR and ACIP vote at future meetingACIP HPV Vaccines Work Group progress\n6\nACIP HPV Vaccines Work Group\nACIP voting members\nOliver Brooks (chair)\nNoel Brewer \nSybil Cineas\nCDC Co -Leads\nCarla DeSisto\nLauri MarkowitzLiaison members\nRobin O'Meara (AAFP)\nAngela Myers (AAP)\nLinda Eckert (ACOG)\nAlfonso Iorio  (ACP)\nJamilia  Sherls  (AIM)\nSandy Fryhofer (AMA)\nSean O'Leary (IDSA)\nNicole Forbes (NACI)\nKevin Ault (NFID)\nAlexandra Yonts  (PIDS)\nNneka Holder (SAHM)\n7Ex-Officio members\nSixun Yang (FDA)\nAimée  R. Kreimer (NIH)\nEleanore  Chuang (NIH)\nConsultant members\nLaura Makaroff (ACS)\nPeter Szilagyi\nRachel Winer\nElizabeth Moore (consumer rep)\nGRADE consultants\nDoug Campos -Outcalt\nRebecca Morgan\nJulia Gargano (DVD)\nRuth Stefanos (DVD)\nVirginia Senkomago (DCPC)\nPatrick Clay (DSTDP)\nHarrell Chesson (DSTDP)\nShannon Stokley (ISD)\nAdefemi  Adeleke (ISD)\nCassandra Pingali (ISD)ACIP HPV Vaccines Work Group - CDC Staff\nElizabeth R. Unger (DHCPP)\nGitika Panicker (DHCPP)\nChristine Olson (ISO)\nJulianne Gee (ISO)\nHannah Rosenblum (ACIP Secretariat)\n8\nToday’s agenda\nIntroduction to policy consideration: \nreduced number of dosesDr. Lauri Markowitz\nCDC/NCIRD\nIntroduction to policy consideration: \nwording of the age for routine vaccinationDr. Ruth Stefanos\nCDC/NCIRD\nReview of literature on HPV vaccination at \nages 9 -10 to increase coverageDr. Sarah Brewer\nCDC/NCIRD\nNext steps Dr. Carla DeSisto\nCDC/NCIRD\n9", "summary": "Introduction to the HPV Vaccines Work Group Oliver Brooks, MD Chair, HPV Vaccines Work Group Advisory Committee on Immunization Practices October 24, 2024 National Center for Immunization & Respiratory Diseases •HPV Vaccines Work Group re -formation announced at June 2024  ACIP meeting •An HPV Vaccines Work Group met previously for many years, but  had been inactive since 2019 •3 meetings since July 2024Background 2 •Routine vaccination -Age 11 or 12 years  -Can be started at age 9 years …", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-23-24-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/01-hpv-Brooks-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 9}
{"title": "02 hpv Markowitz 508", "content": "Introduction to policy considerations: \nReduced number of HPV vaccine doses\nLauri Markowitz, MD\nCo-Lead, HPV Vaccines Work Group\nDivision of Viral Diseases\nAdvisory Committee on Immunization Practices\nOctober 24, 2024National Center for Immunization & Respiratory Diseases\n\n▪Brief introduction to human papillomavirus (HPV)\n▪HPV vaccines and vaccination recommendations in the United States\n▪Overview of data on vaccination with a reduced number of doses \n▪World Health Organization recommendations and international landscape Outline \n2\nIntroduction \n3\n18 years since first HPV vaccine licensure \n▪High vaccine efficacy in clinical trials\n▪High population impact in real world settings \n▪Strong herd effects of vaccination programs\n▪Implementation challenges in many countries\n▪Lag in vaccine introduction in low - and middle -income counties\n4\n\n▪Double -stranded DNA virus (8 kb circular genome)\n▪> 200 closely related types\n•L1 is major capsid protein \n•Sequence of L1 gene determines type\n▪12 types classified as high -risk (oncogenic)\n•HPV 16 and HPV 18 responsible for most HPV -attributable cancer\n▪Low -risk HPV types\n•HPV 6 and HPV 11 cause most anogenital warts and recurrent respiratory \npapillomatosis\n▪Most common sexually transmitted infection\n•~ 13 million persons in the United States become infected with a disease -\ncausing HPV type each year\n•Over 90% become undetectable in 2 years Human papillomaviruses\n5HPVCervical\nOropha\nryngea l\nAnal\nPenileVulvarVaginal\nHPV-attributable cancer\nWright and Schiffman. N Engl J Med 2003\nHPV infection causes cervical cancer (and other cancers) \nafter years to decades\n6\nHPV -associated and estimated HPV -attributable cancer \ncases per year, United States, 2017 –2021\nCancer siteNumber  of HPV -\nassociated \ncancersPercentage \nprobably caused \nby any HPV typeEstimated number probably caused \nby any HPV type*\nFemale Male Both sexes\nCervix 11,959 91% 10,800 - 10,800\nVagina 898 75% 700 - 700\nVulva 4,418 69% 2,900 - 2,900\nPenis 1,381 63% - 900 900\nAnus** 7,854 91% 5,000 2,200 7,200\nOropharynx 21,474 70% 2,300 12,900 15,200\nTOTAL 47,984 79% 21,800 16,000 37,800\n*Estimates were rounded to the nearest 100. Estimated counts might not sum to total because of rounding. \n**Includes anal and rectal squamous cell carcinomas \nSources: Cancers Linked With HPV Each Year | Cancer | CDC   and http://www.cdc.gov/cancer/dataviz  7\nHPV vaccines and recommendations\n8\n▪Virus -like particle (VLP) vaccines \n▪L1 major capsid proteins self -assemble into VLPs\n▪High efficacy with durable protection Available prophylactic HPV vaccines \nHPV VLP\n9\nHPV vaccines licensed in the United States\nVaccine and \nbrand nameBivalent (2vHPV)\nCervarixQuadrivalent (4vHPV)\nGardasil9-valent (9vHPV)\nGardasil 9\nTypes 16, 18 16, 18, 6, 11 16, 18, 6, 11\n31, 33, 45, 52, 58\nPrevents cancer cancer\nanogenital wartscancer\nanogenital warts\nAdjuvant AS04\n500 µg aluminum hydroxide \n50 µg 3-O-desacyl -4’ \nmonophosphoryl lipid AAAHS\n225 µg amorphous aluminum \nhydroxyphosphate  sulfateAAHS\n500 µg amorphous aluminum \nhydroxyphosphate  sulfate\nYear licensed 2009 2006 2014\nManufacturer GlaxoSmithKline Merck & Co. Merck & Co.\nHPV 16 and 18 are oncogenic types that cause most HPV -attributable cancers; HPV 31,33,45,52,58 are oncogenic types that cause ab out 12% of \nHPV -attributable cancers; HPV 6,11 cause most anogenital warts and recurrent respiratory papillomatosis 10\nHPV vaccines licensed in the United States\nVaccine and \nbrand nameBivalent (2vHPV)\nCervarixQuadrivalent (4vHPV)\nGardasil9-valent (9vHPV)\nGardasil 9\nTypes 16, 18 16, 18, 6, 11 16, 18, 6, 11\n31, 33, 45, 52, 58\nPrevents cancer cancer\nanogenital wartscancer\nanogenital warts\nAdjuvant AS04\n500 µg aluminum hydroxide \n50 µg 3-O-desacyl -4’ \nmonophosphoryl lipid AAAHS\n225 µg amorphous aluminum \nhydroxyphosphate  sulfateAAHS\n500 µg amorphous aluminum \nhydroxyphosphate  sulfate\nYear licensed 2009 2006 2014\nManufacturer GlaxoSmithKline Merck & Co. Merck & Co.\n11After the end of 2016, only 9vHPV available in the United States\nEfficacy and immunogenicity trials for initial licensure \nof HPV vaccines, 3 -dose schedules (0, 1 -2, 6 months)\nRandomized controlled efficacy trials \nin ~15 –26-year -old women\nEndpoints: \n- cervical precancers and external \ngenital lesions\nPer protocol analyses: \n- efficacy >96%\n- seroconversion ~ 100 %\nImmunobridging trials in \n9–15-year -olds\nLicensure based on non -\ninferior antibody response \ncompared with women in \nefficacy trials\nFuture II Study Group, NEJM 2007; Garland, et al. NEJM 2007; Paavonen, et al. Lancet 2007 \n  Quadrivalent vaccine trials had other endpoints including, vulvar, vaginal precancers and genital warts12\n2006    2011 2016 2019Females\nRoutine :11or12years , \ncan be started at age 9 \nCatch -up:through 26years \n3-dose scheduleMales \nRoutine :11or12years , \ncan be started at age 9\nCatch -up:through 21years \n3-dose schedule2-dose schedule \niffirst dose  age\n<15 yearsShared  clinical  decision - \nmaking : some  adults\n27 through  45 years\nCatch -up:harmonized \nthrough age 26 yearsEvolution ofHPV vaccination recommendations  – \nUnited States\n13\nCurrent HPV vaccination recommendations, United States\nRecommendations of the Centers for Disease Control and Prevention and the Advisory Committee on Immunization Practices \nhttps://www.cdc.gov/vaccines/hcp/acip -recs/vacc -specific/hpv.htmlRoutine vaccination\n▪Age 11 or 12 years \n▪Can be started at age 9 years \n  Catch -up vaccination \n▪Through age 26 years\n  Shared clinical decision -making \n▪Age 27 –45 yearsNumber of doses\n2 doses  (0, 6 -12 months) \nif starting series before 15th birthday\n3 doses  (0,1-2, 6 months) \nif starting series on or after 15th birthday or \nif immunocompromising condition\n14\n▪Post hoc analyses of a 3 -dose randomized trial (2vHPV vs control vaccine)\n-Not all participants completed 3 -dose schedule \n-Efficacy against HPV16/18 infection similar after 3, 2, 1 doses\n▪Immunobridging trials\n-2 doses  in 9–14-year -olds vs 3 doses in young adult women\n-Seroconversion and GMTs were non -inferior in 2 -dose groupHow did we get to 2 doses? \n15\nJ Natl Cancer  Inst 2011\nGMT ( mMU /mL))Data from 9vHPV \nimmunobridging  trial\nSimilar findings for 2vHPV and 4vHPV: Romanowski, Hum Vaccin  Immunother  \n2016; Puthanakit , JID 2016; Lazcano -Ponce, Vaccine 2014; Dobson, JAMA 2013; \nHernández -Ávila, Hum Vaccin  Immunother  2016; Iversen et al. JAMA 2017HPV type\nIversen  et al. JAMA 20172 doses (0,6 or 0,12 months) in \nadolescents (9 -14 years)\n    compared with \n3 doses (0,2,6 months) \nin women (16 -26 years)\n16\n10100100010000\n6 11 16 18 31 33 45 52 58Girls (0,6) Women (0,2,6)\nLicensure and recommendations for a 2 -dose HPV \nvaccination schedule\nManufacturers  submitted supplemental applications for 2 doses in 9 –14-yr-olds\nFDA and other regulatory authorities approved\nWHO, ACIP , other advisory groups recommended a 2 -dose series at 9 –14 years\n17\n2016 2014\nEvidence on single -dose  vaccination\n18\n▪Stimulated by same studies that led to 2 -dose schedules\n▪Immunobridging trials not possible for single -dose  \n-Single dose results in lower antibody titers than 2 or 3 doses\n-Basis of protection after HPV vaccination thought to be neutralizing antibody\n-No established minimum antibody threshold for protectionSingle -dose  HPV vaccination – initial interest\n19\n\nTrial\nGirls 12–16 years old\n(n=20,300)\nBivalent\n(n=10,150)9-valent\n(n=10,150)\nActive Follow -up \nCervical cells, blood, urine at M12, M18, M24, M30, M36, \nM42, M48, M54, M60M0: Randomized to vaccine\nM6: Randomized to dosing \nschedule\n1 Dose 2 Doses 1 Dose 2 DosesEpidemiologic Surveys\n(unvaccinated)\nHPV infection status\nM0 and M6\nHPV vaccine\nESCUDDO, Costa Rica (data available 2025)\n▪Randomized trial to evaluate non -inferiority of one vs two doses of 2vHPV (Cervarix) and 9vHPV \n(Gardasil 9) for prevention of new cervical HPV16/18 infections that persist at least 6 months\n▪Evaluate one dose compared to zero doses\nClinicalTrials.gov: NCT03180034\n▪Studies that initially provided data had further encouraging data\n▪Recognition of a global HPV vaccine supply/demand imbalance\n▪Additional studies were planned and conducted\n▪Review of data led to revised World Health Organization recommendations \nincluding, “as an off -label option, a single -dose  schedule can be used in girls \nand boys aged 9 –20 years.”Single -dose  HPV vaccination – increasing interest\n21\n\nTrial/country Evidence VaccineAge ( yrs) at \nvaccinationDescription\nCVT \nCosta RicaEfficacy/\nImmunogenicity2vHPV 18–25 Post -hoc analyses  \nOriginal trial: randomized to 3 doses or \ncontrol, but analyzed as 1 -, 2-, 3-dose groups\nIARC -India\nIndiaEfficacy/\nImmunogenicity4vHPV 10–18 Post -hoc analyses\nOriginal trial: randomized to 2 or 3 doses \nbut analyzed as 1 -, 2-, 3-dose groups\nKEN SHE\nKenyaEfficacy 2vHPV \n9vHPV15–20 Randomized trial  \n1 dose 2vHPV, 9vHPV or MCV\nDoRIS \nTanzaniaImmunogenicity 2vHPV \n9vHPV9–14 Randomized trial  \n1-, 2-, 3-dose groups\n22 2vHPV, Cervarix;  9vHPV, Gardasil 9; CVT, Costa Rica Vaccine Trial; IARC, International Agency for Research on CancerTrials with data on single -dose  HPV vaccination \nconsidered by the World Health Organization in 2022\n23Costa Rica Vaccine Trial (CVT)\nProtection  against prevalent HPV after 2vHPV, through 11 years  \nDoses Number Prevalent  16/18 HPV\n%   (95% CI)Vaccine  efficacy\n%   (95% CI)\n3 doses 1365 2.0  (1.3–2.8) 80.0%   (70.7 –87.0)\n2 doses 62 1.6  (0.1–7.7) 83.8% (19.5 –99.2)\n1 dose 112 1.8  (0.3–5.8) 82.1%   (40.2 –97.0)\nUnvaccinated 1783 10.0 (8.7 –11.4) Reference▪Post -hoc analysis of RCT: females vaccinated at age 18 –25 years \n▪Randomized  to receive 3 doses of 2vHPV or control vaccine\nKreimer AR, et al. J Natl Cancer Inst 2020 23\nCosta Rica Vaccine Trial (CVT)\nHPV 16 antibody after 1, 2 or 3 doses of 2vHPV, through 11 years  \nAntibody by VLP -based ELISA at the NCI HPV Immunology Laboratory\nKreimer AR, et al. J Natl Cancer Inst 2020•Stable HPV 16 and 18 \nantibody levels through 11 \nyears post vaccination with \nall dosing schedules\n•1 dose levels at least 10 -fold \nabove level at enrollment \namong unvaccinated \nUnvaccinated \n24\nIARC, International Agency for Research on Cancer\nSankaranarayanan  R, et al. Lancet Oncol  2016IARC -India Trial: provides data on immunogenicity \nand efficacy of 1, 2 and 3 doses of 4vHPV  (Gardasil)  \n2 dose \ngroup\n25Randomized trial \ndesign lost and \nanalyzed as \nobservational \ncohortCluster randomized trial\n2 vs 3 doses of 4vHPV in 10 –18 year -old \nunmarried girls, initiated Sept 2009\nLoss of randomization due to order in April 2010 by \nMinistry of Health to stop HPV vaccination in research studies2 dose \nGroup\n(0,6 months)3 dose \nGroup\n(0,2,6 months)\n251 dose2 doses \n0, 2 months3 doses 2 doses \n0, >6 months\nIARC -India Trial \nProtection after 1, 2 or 3 doses of 4vHPV, through 10 years\nDoses NumberPersistent HPV16/18 Vaccine efficacy\n%   (95% CI)Events %\n3 doses 1460 1 0.07 93.3%  (77.5 –99.9 )\n2 doses 1452 1 0.07 93.1%  (77.3 –99.8 )\n1 dose 2135 1 0.05 95.4%  (85.0 –99.9 )\nControl 1260 32 2.54 Reference\n26Unvaccinated women age -matched to married vaccinated participants recruited as controls\nPersistent infection defined as the same HPV type detected in consecutive samples at least 10 months apart\nVE adjusted for background HPV infection frequency, time between date of marriage and first cervical specimen collection, and  number of cervical specimens per participant\n26IARC, International Agency for Research on Cancer\nBasu P, et al. Lancet Oncol 2021; published correction in Lancet Oncol. 2022 Jan;23(1):e16. IPVC2023 Abstract O177 / #862 . ▪Post hoc analysis of randomized trial: females vaccinated at age 10 –18 years \n▪Randomized to receive 2 or 3 doses 4 vHPV\nSexually active females \naged 15 -20 years\n2275 randomized\n2vHPV \n1 dose9vHPV\n1 doseMeningococcal\n1 dose▪Double -blind, RCT\n▪Sexually active females aged 15 -20 years \n▪Trial groups\n▪2vHPV (Cervarix)\n▪9vHPV (Gardasil 9) \n▪Meningococcal (d elayed HPV vaccination) \n▪Primary objectives \n▪Efficacy in preventing incident persistent infection*\n–HPV-16/18\n–HPV-16/18/31/33/45/52/58 KEN SHE Trial - Kenya\nBarnabas R, et al.  NEJM Evidence 2022    *Defined as vaccine -type specific HPV detected at two consecutive time points no less than 4 months apart\n 27\nKEN SHE: RCT of single -dose  HPV vaccination\nIncident persistent 16/18 infections and vaccine efficacy\n18 months 36 months\nVaccine NIncident \npersistent \nHPV 16/18Incidence/\n100 PYVE % \n(95% CI)Incident \npersistent \nHPV 16/18Incidence/\n100 PYVE % \n(95% CI\n9vHPV 496 1 0.1797.5%  \n(81.7 –99.7)1 0.0898.8%  \n(91.3 –99.8)\n2vHPV 489 1 0.1797.5%  \n(81.6 –99.72 0.1697.5%  \n(90.0 –99.4)\nMeningococcal 473 36 6.83 Reference 72 6.70 Reference▪1458  evaluated f or efficacy  in mITT  cohort\n28 Barnabas R, et al. Nature Medicine 2023Enrollment criteria: 1 -5 lifetime partners; HIV negative;  enrollment between December 2018 and June 2021\nMCV, meningococcal vaccine;  mITT , modified intention to treat: HPV 16/18 HPV DNA negative (external genital and \ncervical swabs) at enrollment and month 3 (self -collected vaginal swab) and HPV antibody negative at enrollment\nPY, person years \n \nBarnabas R, et al. NEJM Evidence 2022    \nThrough three years after vaccination , 1-dose HPV vaccine efficacy remained high\nBarnabas R, et al. Nature Medicine 20239v VE= 99%  for HPV 16/18 (95% CI: 91 – 100%)\n2v VE= 98%  for HPV 16/18 (95% CI: 90 – 99%)\nVE=96%  for HPV 16/18/31/33/45/52/58 \n(95% CI: 89 – 98%)\n29KEN SHE: RCT of single -dose  HPV vaccination\nDoRIS  - Tanzania\n▪Dose Reduction Immunobridging & Safety Study \n▪Randomized, open label trial in girls aged 9 -14 years\n▪1, 2, 3 doses of 2vHPV (Cervarix)  or 9vHPV (Gardasil 9)\n▪Objectives – demonstrate noninferiority\n–HPV 16 and 18 antibody response after 1 vs 2 or 3 doses of same vaccine\n–HPV 16 and 18 GMCs: 1 dose in DoRIS  vs 1 dose in studies that evaluated efficacy \nGMC, geometric mean concentration30Girls aged 9 -14 years\nN=930\n2vHPV \n1 dose2vHPV\n2 doses2vHPV\n3 doses9vHPV\n1 dose9vHPV\n2 doses9vHPV \n3 doses\nDoRIS  conclusions\n31\n Watson -Jones D, et al. Lancet Global Health 2022     \nDoRIS  conclusions\n▪Seropositivity >97. 8%after vaccination for all vaccine groups\n32 Watson -Jones D, et al. Lancet Global Health 2022     \nDoRIS  conclusions\n▪Seropositivity  >97.8%  after vaccination for all vaccine groups\n▪Antibody levels  lower after 1 dose compared with 2 or 3 doses\n•Kinetics, with plateau, similar for all doses\n33\n Watson -Jones D, et al. Lancet Global Health 2022     9vHPV vaccine groups\nDoRIS  conclusions\n▪Seropositivity >97. 8%after vaccination for all vaccine groups\n▪Antibody levels  lower after 1 dose compared with 2 or 3 doses\n•Kinetics, with plateau, similar for all doses\n▪ Avidity for each HPV type was similar for 3, 2 and 1 doses for both vaccines \n34 Watson -Jones D, et al. Lancet Global Health 2022     \n\nDoRIS  conclusions\n▪Seropositivity >97.8% after vaccination for all vaccine groups\n▪Antibody levels  lower after 1 dose compared with 2 or 3 doses\n•Kinetics, with plateau, similar for all doses\n▪Avidity for each HPV type was similar for 3, 2 and 1 doses for both vaccines . \n▪Immunobridging : 1-dose responses were non -inferior in DoRIS  (9-14 year -olds) \ncompared with those among women in studies where 1 -dose efficacy observed\n \n35\nLancet Global Health 2024     \nHPV 16 and 18 antibodies measured by ELISA at Frederick National Laboratory for Cancer Research HPV Immunology Laboratory, USA\nStudy/\ncountryEvidence VaccineAge ( yrs) at \nvaccinationDescription\nHOPE \nSouth AfricaImpact/ \nEffectiveness2vHPV 15–16 1 dose as catch -up in grade 10. Baseline and cross \nsectional prevalence surveys; includes WLWH\nThailand Impact \nThailand   Effectiveness 2vHPV Grade 8\nage <15 yrs1 or 2 doses, by province; Baseline and post -\nvaccination cross sectional prevalence surveys\nHANDS\nThe GambiaImmunogenicity 9vHPV 4–8, 9–14 \n15–26Randomized trial of 1 or 2 doses vs\n3 doses in 15 –26-year -olds\nPrimavera\nCosta RicaImmunogenicity 2vHPV \n9vHPV9–14\n18–251 dose\n3 doses\nPRISMA\nCosta  RicaEfficacy 2vHPV \n4vHPV\n9vHPV18–30 Randomized trial of 1 dose of three different HPV \nvaccines vs unvaccinated  \nESCUDDO\nCosta  RicaEfficacy/\nImmunogenicity2vHPV \n9vHPV12–16 Randomized trial of 1 vs 2 dosesAdditional studies evaluating single -dose  HPV \nvaccination, data forthcoming \n36 2vHPV, Cervarix;  9vHPV, Gardasil 9;  WLWH, women living with HIV; RCT, randomized controlled trial. All studies conducted among girls/women \nStudy/\ncountryEvidence VaccineAge ( yrs) at \nvaccination  Data expected\nCVT\nCosta  RicaEfficacy/\nImmunogenicity2vHPV 12–16 14-, 16- and 20 -year data\nIARC -India\nIndia Efficacy/\nImmunogenicity4vHPV 10-18 12-year data and further\nDoRIS\nTanzaniaImmunogenicity 2vHPV\n9vHPV9-14 36- and 60 -month dataAdditional data from studies reviewed today\n372vHPV, Cervarix;  9vHPV, Gardasil 9 \nWLWH, women living with HIV; RCT, randomized controlled trial. All studies conducted among girls/women \n▪Studies of single -dose  also provide data on a 2 -dose schedule \n•Studies with a 2 -dose group (0, 6 months)\n–CVT (2vHPV): 18 –25-year -olds\n–IARC -India (4vHPV): 10 –18-year -olds\n▪Immunogenicity trial of 2 vs 3 doses of 9vHPV*\n•U.S. study in 15 –26-year -olds\n•Ongoing - interim data published Two HPV vaccine doses for persons aged >15 years\n38 *Berenson A, et al. NEJM Evidence 2024\n2022 World Health Organization  \nrecommendations and global landscape\nWHO recommendations forHPV vaccination\nDecember 2022:\nEvidence supports a 2-dose schedule from\nage 9years and for allolder agegroups for\nwhich HPV vaccines arelicensed.\nAsanoff-label option, asingle -dose\nschedule can beused ingirls and boys\naged 9–20years.\n40\nDate: October  2024 41\nDoses -intervalNo. of \ncountries\n1 dose 58\n2 doses (12 months) 5\n2 doses (6 months 76\nNot yet introduced 50\nUnknown schedule 5Recommended HPV vaccine schedules in 9‒14 -year -olds, \nby country\n▪Some of the first countries to change to a routine single -dose  schedule\n–England, Ireland, Australia\n▪Change from a 3 -dose to a 2 -dose schedule for persons ages >14 years\n–Netherlands and Sweden\n▪Single -dose  recommendations by regional advisory groups\n–PAHO in 2023 and AFRO in 2024Policy changes since updated WHO HPV vaccination \nrecommendations in 2022\n42PAHO Technical Advisory Group recommends countries of the Americas to use single -dose  HPV vaccine schedule | OPS/OMS | Organisation  panaméricaine  de la santé\nAfrica immunization advisory group urges single -dose  HPV vaccine adoption to advance vaccination efforts | WHO | Regional Office for Africa\n▪Longer term efficacy and immunogenicity\n▪Protection at sites other than the cervix\n▪Efficacy and immunogenicity in males*\n▪Efficacy and immunogenicity in immunocompromised persons\n▪Efficacy and immunogenicity in older age groupsOutstanding questions for single -dose  vaccination ?\nAdditional data expected over the next year will \naddress some of these questions \n* Data available from a small immunogenicity trial in 11 –12-year -old girls and boys: Zeng et al. Pediatrics 2023 43\n▪Plan to conduct two prospective clinical trials, one in females (16 -26 years) \nand one in males (ages 16 -26 years).\n▪These randomized, double -blind, multi -year clinical trials will examine the \nshort and long -term efficacy and immunogenicity of a single -dose  of Gardasil 9 \nversus the currently approved three -dose regimen.\n▪Merck is in discussions with FDA about the protocols and the timeline. \nMerck Announces Plans to Conduct Clinical Trials of a Novel Investigational Multi -Valent Human Papillomavirus (HPV) \nVaccine and Single -Dose Regimen for GARDASIL®9 Announcement from Merck, March 2024\n44\n▪HPV vaccines were first studied and licensed in a 3 -dose schedule in persons \naged 9 –26 years and later in a 2 -dose schedule in persons aged 9 –14 years.  \n▪Data are available on single -dose  HPV vaccination, including from a RCT with 3 \nyears of follow -up, showing high efficacy against incident persistent infection. \n▪Long term follow -up suggests protection for >10 years with a single dose.\n▪WHO 2022 updated recommendations: 2 doses for persons aged 9 years and \nolder, with option for single -dose  HPV vaccination through age 20 years, \nexcept those immunocompromised.\n▪Countries are considering new or updated HPV vaccination policy and an \nincreasing number have recommended single -dose  HPV vaccination.\n▪Further data on 1 and 2 doses will be available over the next year. Summary \n45\n\n▪Review further evidence \n•1- and 2 -dose schedules\n•Modeling data\n•Other relevant data\n▪Evaluate evidence using GRADE and evaluate policy questions using the \nEvidence to Recommendations framework\n•Should a 1 -dose schedule be recommended in some age groups?\n•Should a 2 -dose schedule, instead of a 3 -dose schedule, be recommended in \nsome age groups older than 9 –14 years?Next steps for ACIP HPV Vaccines Work Group\n46\nWhat questions does ACIP have regarding the policy \nquestions being addressed? Questions for ACIP\n47\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the \nofficial position of the Centers for Disease Control and Prevention.Thank You", "summary": "Introduction to policy considerations:  Reduced number of HPV vaccine doses Lauri Markowitz, MD Co-Lead, HPV Vaccines Work Group Division of Viral Diseases Advisory Committee on Immunization Practices October 24, 2024National Center for Immunization & Respiratory Diseases  ▪Brief introduction to human papillomavirus (HPV) ▪HPV vaccines and vaccination recommendations in the United States ▪Overview of data on vaccination with a reduced number of doses  ▪World Health Organization recommendations…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-23-24-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/02-hpv-Markowitz-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 48}
{"title": "03 hpv Stefanos 508", "content": "Introduction to policy consideration: \nWording of the age for routine vaccination\nRuth Stefanos, MD, MPH\nLCDR, US Public Health Service\nDivision of Viral Diseases\nAdvisory Committee on Immunization Practices\nOctober 24, 2024National Center for Immunization and Respiratory Diseases\n1\nOutline\n•Current recommendation and historical context\n•Clinical Decision Support for Immunization project\n•Vaccination coverage\n•Interest in vaccination at age 9 years\n2\nCurrent Recommendation\nhttps://www.cdc.gov/acip -recs/hcp/vaccine -specific/hpv.html•HPV vaccination is routinely recommended at age 11 or 12 years\n•Vaccination can be given starting at age 9 years\n•Since 2006 (first ACIP recommendation), the wording of age at HPV \nvaccination initiation has not substantially changed\n3\n1996 “This report presents a new strategy to improve the delivery of vaccination services to \nadolescents and to integrate recommendations for vaccination with other preventive \nservices provided to adolescents. This new strategy emphasizes vaccination of adolescents \n11-12 years of age by establishing a routine visit to their health -care providers.” \nImmunization of adolescents. MMWR Recomm Rep. 1996;45(RR -13):1 -16.\n2005 “The preferred age for Tdap vaccination is 11 –12 years” \nBroder KR, Cortese MM, Iskander JK, et al. MMWR Recomm Rep. 2006;55(RR -3):1-34.\n\"Introducing a recommendation for MCV4 vaccination among young adolescents might \nstrengthen the role of the preadolescent visit and have a positive effect on vaccine coverage \namong adolescents.”\nBilukha OO, Rosenstein N. MMWR Recomm Rep. 2005;54(RR -7):1-21.\n2006 “ACIP recommends routine vaccination of females aged 11 –12 years with 3 doses of \nquadrivalent HPV vaccine. The vaccination series can be started as young as age 9 years.”\nMarkowitz LE, Dunne EF, Saraiya M, et al. MMWR Recomm Rep. 2007;56(RR -2):1-24.Adolescent Platform\nAdolescent \nPlatform\nTdap\nMCV4\nHPV\n4\nhttps://www.cdc.gov/hpv/hcp/vaccination -considerations/boost -rates.htmlAdolescent Platform\n5\nCurrent HPV Vaccination Recommendations\nhttps://www.cdc.gov/acip -recs/hcp/vaccine -specific/hpv.htmlRoutine VaccinationAge 11–12 years,\ncan be started at age 9 years\nCatch -Up VaccinationAge 13–26 years,\nif not adequately vaccinated\nShared Clinical Decision -MakingSome adults age 27–45 years,\nif not adequately vaccinated\nSpecial situation:\nHistory of sexual abuse or assault: Start at age 9 years\n6\nNotes and full schedule available at: https://www.cdc.gov/vaccines/hcp/imz -schedules/child -adolescent -age.htmlVaccine Birth 1 \nmo2 \nmos4 \nmos6 \nmos9 \nmos12 \nmos15 \nmos18 \nmos19–\n23 \nmos2–3 \nyrs4–6 \nyrs7–10 yrs 11–\n12 \nyrs13–\n15 \nyrs16 \nyrs17–\n18 \nyrs\nHPVSee \nnotes\nRange of \nrecommended \nages for all \nchildrenRange of \nrecommended \nages for catch -\nup vaccinationRange of \nrecommended \nages for \ncertain high -\nrisk groupsRecommended \nvaccination can \nbegin in this age \ngroupRepresentation of HPV Vaccination Recommendations \non Child and Adolescent I mmunization Schedule\n7\nRecommended Immunizations for Children 7‒18 Years Old\nParent -Friendly Schedule\nhttps://www.cdc.gov/vaccines/imz -schedules/adolescent -easyread.html8\n\nClinical Decision Support for Immunization (CDSi)\n•Logic for applying ACIP rules to CDS \nengines \n•For HPV vaccine:\n•Minimum age: 9 years\n•Earliest recommended age: 11 years\n•Prompt for HPV vaccination occurs at \nearliest recommended age (11 years)\n9https://www.cdc.gov/iis/cdsi/\nEstimated Vaccination Coverage, Adolescents Aged 13 –17 Years, \nNational Immunization Survey -Teen, United States, 2006 –2023\nPingali et al. MMWR  2024    UTD: up -to-date0102030405060708090100\n2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023Percent Vaccinated\nSurvey Year≥1 HPV (females, 79%)\n≥1 HPV (males, 75%)\nHPV UTD (females, 64%)\nHPV UTD (males, 59%)≥1 Tdap\n≥1 MenACWYHPV vaccination  \nrecommendation \nfor malesHPV vaccination  \nrecommendation\nfor females\n10\nAmerican Academy of Pediatrics Recommendations\n•Beginning in the 2018 –2021 Redbook, HPV vaccination recommendation language \nwas modified.\n \n“The AAP recommends starting the series between 9 and 12 years, at an age that the \npediatric health care professional deems optimal for acceptance and completion of \nthe vaccination series.” \nAmerican Academy of Pediatrics. Red Book: 2024 -2027 Report of the Committee on Infectious Diseases (33rd Edition)11\nInterest in V accination at Age 9\nhttps://www.tandfonline.com/journals/khvi20/collections/HPV -vaccination -starting -age-912\nPolicy Question\nShould the ACIP recommendations state:\nHPV vaccination is routinely recommended at age 9 –12 years\n  instead of\nHPV vaccination is routinely recommended at age 11 or 12 years; \nvaccination can be given starting at age 9 years\n13\nACIP HPV Vaccines Work Group Next Steps\n•Review literature \n-Systematic review (completed by CDC)\n-Will be presented today\n•Review other data\n-NIS-Teen\n-Randomized Controlled Trial (f inal data not available until 2026)\n•Conduct modified Evidence to Recommendations (EtR)\n14\n15•4 countries: begin at age 9 years\n•6 countries: begin at age 10 years\n•20 countries: begin at age ≥11 years\n•UK: age 12 –13 years\n9 10 11 12 13 14 15 16 17 18\nAustria\nBelgium  \nBulgaria\nCroatia\nCyprus\nCzechia\nDenmark\nEstonia\nFinland\nFrance\nGermany\nGreece\nHungary\nIceland\nIreland\nItaly\nLatvia\nLiechtenstein\nLithuania\nLuxembourg\nMalta\nNetherlands\nNorway\nPoland\nPortugal\nRomania\nSlovakia\nSlovenia\nSpain\nSwedenCountry Age (years)\ngraph adapted from https://vaccine -schedule.ecdc.europa.eu/Scheduler/ByDisease?SelectedDiseaseId=38&SelectedCountryIdByDisease= -1\nhttps://www.gov.uk/government/publications/hpv -universal -vaccination -guidance -for-health -professionals/hpv -vaccination -guidance -for-healthcare -practitioners\nPolicy Question\nShould the ACIP recommendations state:\nHPV vaccination is routinely recommended at age 9 –12 years\n  instead of\nHPV vaccination is routinely recommended at age 11 or 12 years; \nvaccination can be given starting at age 9 years\n16\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention.\nAcknowledgments\nSarah Brewer, PhD, MPH\nCarla DeSisto, PhD, MPH\nJulia Gargano, PhD\nLauri Markowitz, MD\n17", "summary": "Introduction to policy consideration:  Wording of the age for routine vaccination Ruth Stefanos, MD, MPH LCDR, US Public Health Service Division of Viral Diseases Advisory Committee on Immunization Practices October 24, 2024National Center for Immunization and Respiratory Diseases 1 Outline •Current recommendation and historical context •Clinical Decision Support for Immunization project •Vaccination coverage •Interest in vaccination at age 9 years 2 Current Recommendation…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-23-24-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/03-hpv-Stefanos-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 17}
{"title": "04 hpv Brewer 508", "content": "Human papillomavirus vaccination at age 9 or 10 years \nto increase coverage – a systematic review and \nnarrative review of the literature \nSarah Brewer, PhD, MPH\nDivision of Viral Diseases\nAdvisory Committee on Immunization Practices\nOctober 24, 2024 National Center for Immunization & Respiratory Diseases\n\nBackground\n2\n•Since HPV vaccine was first licensed and recommended in 2006 for females, the wording of the \nroutine age recommendation has remained the same\n•While HPV vaccination coverage has increased since HPV vaccination was first recommended, \nuptake continues to be lower than other vaccines recommended in adolescence\n•There have been many efforts to increase HPV vaccination in the United States\n•In the past few years there has been increasing enthusiasm for HPV vaccine initiation at age 9 \nyears to increase coverage Background\n3\n•Critically evaluate publications investigating HPV vaccination at age 9 –10 years\n-Systematic review and narrative summary of literature\n-Describe methodologies used\n-Provide data summaries and interpretationsObjective\n4\nSelection criteria\n•Dates and location: 2014 –2024, United States\n•Population:\n-Individuals ≥9 years of age who are eligible to receive HPV vaccination\n-Parents/caregivers of persons ≥9 years of age\n-Clinicians, providers, or other clinical staff who administer the HPV vaccine\n•Evaluation:\n-HPV vaccination at ages 9 –10 years\n•Outcomes:\n-HPV vaccine initiation\n-HPV vaccine series completion\n-Acceptability among providers and caregivers of routine HPV vaccination at ages 9 –10 years\n-Feasibility of routine HPV vaccination at ages 9 –10 years where HPV vaccination is offered\n5\nPRISMA flow chart for study inclusion in systematic review\n6\n\nStudy descriptionsStudy Completion Initiation Provider \nperspectives/behaviorCaregiver \nperspectives\nKajtezovic  2023 X\nSaxena 2023 X\nSt. Sauver 2016 X\nGoodman 2023 X\nMinihan  2023 X\nHirth  2024 X\nBednarczyk  2023 X\nLiu 2016 X\nInguva  2020 X\nKashani  2019 X\nDonahue 2015 X\nPerkins 2020 X X\nZorn 2022 X X\nGoleman 2018 X\nCox 2022 X X\nO’Leary 2023 X X\nCasey 2022 X X\nHuang 2023 X X\nChristensen 2023 X\nStrasel 2023 X\nIsher -Witt 2023 X\nBrodie 2018 X\nBowden 2017 X\nKong 2022 X\nBiancarelli 2020 X\nVielot 2023 X\nLake 2023 X\nKahn 2023 X\nKohler 2023 X\nAragones 2022 XRetrospective cohort/ \nobservational coverage \nstudies\nQuality \nimprovement/intervention \ncoverage projects\nProvider/caregiver \nbehavior and perspectives \n7\nRetrospective cohort/observational studies (N=11)\nStudy Completion Initiation Provider \nperspectives\n/behaviorCaregiver \nperspectives\nGoodman X\nMinihan X\nBednarczyk X\nHirth X\nKajtexovic X\nSaxena X\nLiu X\nSt. Sauver X\nInguva X\nKashani X\nDonahue XNIS-Teen\nMarketscan\nOther\n8\n9 explored impact of initiation at age 9 –10 vs. age ≥11 years on completion or up -to-date \nstatus of the vaccination series\n-Many looked at series completion by age 13, but others evaluated up -to-date status at older ages \nor used an outcome defined by time to complete the series after receiving first dose\n-All but one found higher on time completion of the HPV vaccination series when initiated at ages \n9–10 years\n-1 also assessed impact of age at initiation on association between race/ethnicity and series \ncompletion; increased odds of series completion across all racial/ethnic groups when initiating at \nage 9 –10 years compared to age 12 years\n1 assessed association of initiation timing in relation to other routine adolescent vaccines \non series completion \n-HPV vaccine series completion higher if HPV vaccination initiated before Tdap or meningococcal \n1 investigated predictors of initiation for children aged 9 –13 \n-The same characteristics were associated with initiation, regardless of age at initiationSummary: retrospective cohort/observational studies \n(N=11)\n9\nInterpretation: retrospective cohort/observational \nstudies (N=11)\n10 *Some studies evaluated completion, but not by age 13 yearsHigher vaccination series completion* when initiating at age 9 –10 vs. 11 –12, \nbut study limitations preclude a cause -and-effect interpretation\nA small percentage of vaccinated adolescents had initiated at age 9 –10 in \nmost studies (2 –8%)\nNo information on reasons for initiation at age 9 –10; may have been \ndifferences in those initiating at age 9 –10 vs. 11 –12\nThere may be differences between providers vaccinating at age 9 –10 and \nthose vaccinating at age 11 –12\nQuality improvement/intervention (N=12)\nStudy Completion Initiation Provider \nperspectives\n/behaviorCaregiver \nperspectives\nPerkins X X\nZorn X X\nGoleman X\nCox X X\nO’Leary X X\nCasey X X\nHuang X X\nChristensen X\nStrasel X\nIsher -Witt X\nBrodie X\nBowden X\n11\nAll 12 studies evaluated initiation:\n-Interventions were multipronged, with one component focused on initiation at ages 9 –10 years\n-All studies observed an increase in initiation for all ages at initiation (9 –10 years and ≥11 years), \nor at a clinic population level\n•Magnitude of increases varied across age groups\n•Increases were not sustained in all studies\n•Initiation rates at 9 –10 years still lower than initiation at ≥11 years\n6 Studies evaluated initiation and completion:\n-Increases in completion rates observed in the majority of studiesSummary: quality improvement/intervention studies \n(N=12)\n12\nQuality improvement/intervention (N=12)\nN=6 Focus on initiation  only\nAuthor EMR\nchangeProvider/ \nstaff \ntrainingPatient \neducationQI team/ \ndata \nfeedbackClinic \nincentivesStanding \nordersPatient \nreminders\nGoleman x x x x\nIsher -Witt x x x x\nStrasel x x\nChristensen x*\nBrodie x x\nBowden x x x x\n*Analysis attempted to measure association with change in electronic medical record (EMR) only, but there may have been other  undocumented \nconcurrent events that influenced HPV initiations that were not incorporated into the model\n13\nQuality improvement/intervention (N=12)\nN=6 Focus on both initiation  and completion\nAuthor EMR \nchangeProvider\n/staff \ntrainingPatient \neducationQI team/ \ndata \nfeedbackClinic \nincentivesStanding \nordersPatient \nreminders\nPerkins x x x x x\nCasey x x x x x\nZorn x x x\nCox x x x x x x x\nHuang x x x x\nO’Leary x x\n14\nIn the majority of QI/Intervention studies, there were increases \nin initiation and completion; however:\n•Due to multi -pronged interventions, it is unclear if the component focused on \ninitiation at ages 9 –10 was responsible for any of the increase in coverage\n•Within the QI/Intervention studies, vaccination at age 9 was feasible, but not \nnecessarily better than at ages 11 –12Interpretation: quality improvement/intervention \nstudies (N=12)\n15\nProvider/caregiver perspectives and behavior studies\nStudy Completion Initiation Provider \nperspectives/\nbehaviorCaregiver \nperspectives\nVielot X\nBiancarelli X\nKong X\nLake X\nKahn X\nKohler X\nAragones XInterviews: \nProviders\nSurveys: \nProviders\nInterview/ \nSurvey: \nCaregivers\n16\n2 Clinician Interviews :\n-1 intervention study: providers reported a positive experience with recommending vaccination at age 9–10 \n-1 qualitative study: providers had mixed opinions \n3 Clinician Surveys :\n-1 survey: among not currently recommending at age 9, family medicine physicians were more willing to \nrecommend the vaccine at ages 9 –10 \n-1 survey: strong recommendation differed by age group and specialty\n-1 survey: recommendation framing mattered when initiating at ages 9 –10\n-Perceived benefits of vaccination varied by initiation age\n2 Caregiver Studies:\n-Few caregivers reported receiving information or recommendations to vaccinate children before age 11\n-Most reported willingness to vaccinate at ages 9 –10Summary: provider/caregiver behavior and perspective \nstudies (N=7)\n17\nInterpretation: provider/caregiver behavior and \nperspective studies (N=7)\n18In limited settings, and mostly small studies, vaccination at ages 9 –10 \nyears was acceptable by caregivers and providers\n•We conducted a systematic review evaluating HPV vaccination at ages 9 –10 years\n•Data from 30 studies published 2014 –2024 were summarized in a narrative review \n•3 general types of studies\n-Within retrospective cohort studies, HPV vaccine initiation at ages 9 –10 years was associated with higher \ncompletion by age 13; this was a small proportion of initiators in all studies\n•There could  have been meaningful differences between children initiating at ages 9 –10 vs 11 –12 \nor providers vaccinating at ages 9 –10 vs those vaccinating at the routine age\n-Within  QI/ intervention studies findings show vaccination  at age 9  was feasible , but not necessarily better\n•Due to the multifaceted approaches; contribution of the recommendation for initiation at age 9 –\n10 years on increases in coverage is unclear\n-Vaccination at ages 9 –10 years may be acceptable to caregivers and providersOverall summary\n19\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention.\nAcknowledgements\nRuth Stefanos\nLauri Markowitz\nShannon Stokley\nNeil C. Murthy\nAmimah Asif\n21Kajtezovic , S., et al. (2023). \"Optimizing timing of adolescent vaccines: Impact of initiating HPV vaccination before Tdap or meningoco ccal vaccination \non timely completion of the HPV vaccine series.\" Hum Vaccin  Immunother . 19(1): 2175541.\n \nSaxena, K., et al. (2023). \"HPV vaccine initiation at 9 or 10 years of age and better series completion by age 13 among priva tely and publicly insured \nchildren in the US.\" Hum Vaccin  Immunother . 19(1): 2161253.\n \nSt. Sauver, J. L., et al. (2016). \"Younger age at initiation of the human papillomavirus (HPV) vaccination series is associat ed with higher rates of on -time \ncompletion.\" Prev Med.  89: 327 -333.\n \nGoodman, E., et al. (2023). \"Early Initiation of HPV Vaccination and Series Completion in Early and Mid -Adolescence.\" Pediatrics  151(3): e2022058794.\n \nMinihan , A. K., et al. (2023). \"The association of initiating HPV vaccination at ages 9 –10 years and up -to-date status among adolescent s ages 13 –17 \nyears, 2016 -2020.\" Hum Vaccin  Immunother . 19(1): 2175555.\n \nHirth , J., et al. (2024.). \"Effect of age at initiation of the human papillomavirus vaccine on the association between race/ethnic ity and completion of \nthe vaccine series.\" Vaccine .\n \nBednarczyk , R. A. and H. M. Brandt (2023). \"Descriptive epidemiology of age at HPV vaccination: Analysis using the 2020 NIS -Teen.\" Hum Vaccin  \nImmunother . 19(1): 2204784.\nLiu, G., et al. (2016). \"HPV vaccine completion and dose adherence among commercially insured females aged 9 through 26 years  in the US.\" \nPapillomavirus Res.  2: 1-8.\nInguva , S., et al. (2020). \"Factors influencing Human papillomavirus (HPV) vaccination series completion in Mississippi Medicaid.\" Vaccine  38(8): 2051 -\n2057.\n \nKashani , B. M., et al. (2019). \"Human Papillomavirus Vaccination Trends, Barriers, and Promotion Methods Among American Indian/Alask a Native and \nNon -Hispanic White Adolescents in Michigan 2006 –2015.\" J Community Health.  44(3): 436 -443.\n \nDonahue, K. L., et al. (2015). \"Human papillomavirus vaccine initiation among 9 –13-year -olds in the United States.\" Prev Med Rep.  2: 892 -898.\n References – Retrospective/cohort studies\n22Perkins, R. B., et al. (2020). \"Improving HPV vaccination rates: a stepped -wedge randomized trial.\" Pediatrics  146(1).\n \nZorn, S., et al. (2023). \"Multi -level quality improvement strategies to optimize HPV vaccination starting at the 9 -year well chi ld visit: Success stories from \ntwo private pediatric clinics.\" Hum Vaccin  Immunother . 19(1): 2163807.\n \nGoleman, M. J., et al. (2018). \"Quality improvement initiative to improve human papillomavirus vaccine initiation at 9 years of age.\" Acad  Pediatr . 18(7): \n769-775.\n \nCox, J. E., et al. (2022). \"Improving HPV vaccination rates in a racially and ethnically diverse pediatric population.\" Pediatrics  150(4): e2021054186.\n \nO’Leary, S. C. and H. M. Frost (2023). \"Does HPV vaccination initiation at age 9, improve HPV initiation and vaccine series c omp letion rates by age 13?\" \nHuman vaccines & immunotherapeutics  19(1): 2180971.\n \nCasey, S. M., et al. (2022). \"Long -term multilevel intervention impact on human papillomavirus vaccination rates spanning the CO VID-19 pandemic.\" Journal \nof Lower Genital Tract Disease  26(1): 13 -19.\n \nHuang, E., et al. \"HPV Vaccine Completion by 13: a Quality Improvement Initiative in a Large Primary Care Network.\" Academic pediatrics .\n \nChristensen, T., et al. (2023). \"Effect of immunization registry -based provider reminder to initiate HPV vaccination at age 9, W ashington state.\" Hum Vaccin  \nImmunother . 19(3): 2274723.\n \nStrasel, M., et al. (2023). \"HPV vaccination rates in 9 -and 10 -year -olds following a pharmacist -led intervention.\" J Am Pharm Assoc.\n \nIsher -Witt, J., et al. (2023). \"Age nine is possible: Improving age 9 HPV initiation through a national quality improvement init iative during the COVID -19 \npandemic.\" Hum Vaccin  Immunother . 19(3): 2284359.\n \nBrodie, N. and K. E. McPeak (2018). \"Improving Human Papilloma Virus Vaccination Rates at an Urban Pediatric Primary Care Cen ter.\" Pediatr  Qual Saf. 3(5): \ne098.\nBowden, M., et al. (2017). \"Improving Human Papilloma Virus Vaccination Rates: Quality Improvement.\" Pediatr  Qual Saf. 2(6): e048.\n References – Quality improvement/intervention studies\n23Kong, W. Y., et al. (2022). \"Recommending human papillomavirus vaccination at age 9: a national survey of primary care profes sionals.\" Acad  Pediatr . \n22(4): 573 -580.\n \nBiancarelli, D. L., et al. (2020). \"Provider experience recommending HPV vaccination before age 11 years.\" J Pediatr . 217: 92-97.\n \nVielot, N. A., et al. (2023). \"Acceptability and readiness to promote human papillomavirus vaccination at ages 9 –10 years: a fea sibility study among North \nCarolina clinics.\" Pilot Feasibility Stud.  9(1): 153.\n \nLake, P., et al. (2023). \"HPV vaccine recommendations by age: A survey of providers in federally qualified health centers.\" Hum Vaccin  Immunother . \n19(1): 2181610.\n \nKahn, B. Z., et al. (2023). \"Framing of national HPV vaccine recommendations and willingness to recommend at ages 9 -10.\" Hum Vaccin  Immunother . \n19(1): 2172276.\n \nKohler, R. E., et al. (2023). \"Mothers’ perceptions and attitudes about HPV vaccination initiation among 9 - and 10 -year -olds.\" Hum Vaccin  Immunother . \n19(3): 2270842.\n \nAragones, A., Gany , F., Kaplan, A., & Bruno, D. (2022). An opportunity to increase human papillomavirus vaccination rates: Change the guideline s. Hum \nVaccin  Immunother ., 18(6), 2136444. https://doi.org/10.1080/21645515.2022.2136444 References – Provider/caregiver behavior and perspectives studies", "summary": "Human papillomavirus vaccination at age 9 or 10 years  to increase coverage – a systematic review and  narrative review of the literature  Sarah Brewer, PhD, MPH Division of Viral Diseases Advisory Committee on Immunization Practices October 24, 2024 National Center for Immunization & Respiratory Diseases  Background 2 •Since HPV vaccine was first licensed and recommended in 2006 for females, the wording of the  routine age recommendation has remained the same •While HPV vaccination coverage…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-23-24-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/04-hpv-Brewer-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 23}
{"title": "05 hpv DeSisto 508", "content": "HPV Vaccines Work Group – Next Steps\nCarla L. DeSisto, PhD, MPH\nCo-Lead, HPV Vaccines Work Group\nAdvisory Committee on Immunization Practices\nOctober 24, 2024\nNational Center for Immunization & Respiratory Diseases\n•Number of doses in the recommended HPV vaccination series:\n-Started GRADE process, planning full Evidence to Recommendations ( EtR) framework\n-February 2025 ACIP meeting: plan to share additional data from trials/studies, \nmodeling, and partial EtR\n•Wording of the age for routine HPV vaccination:\n-Reviewed related literature\n-Not using GRADE, planning modified EtR \n-February 2025 ACIP meeting: plan to share partial EtR\n•Plan for ACIP vote: both issues at the same meeting (not February 2025)ACIP HPV Vaccines Work Group next steps\n2\nWhat questions does ACIP have regarding the policy questions to be \naddressed?Questions for ACIP", "summary": "HPV Vaccines Work Group – Next Steps Carla L. DeSisto, PhD, MPH Co-Lead, HPV Vaccines Work Group Advisory Committee on Immunization Practices October 24, 2024 National Center for Immunization & Respiratory Diseases •Number of doses in the recommended HPV vaccination series: -Started GRADE process, planning full Evidence to Recommendations ( EtR) framework -February 2025 ACIP meeting: plan to share additional data from trials/studies,  modeling, and partial EtR •Wording of the age for routine…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-23-24-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/05-hpv-DeSisto-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 3}
{"title": "01 cmv Jamieson 508", "summary": "ACIP material — 7 pages. CDC vaccine advisory committee document. Open the PDF to read.", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-23-24-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/01-cmv-Jamieson-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 7}
{"title": "01 MPOX Rao 508", "content": "Clade I Mpox Outbreak:  \nSituational UpdateCenters for Disease Control and Prevention\nAgam Rao, MD\nCAPT, U.S. Public Health Service\nChief Medical Officer, Poxvirus and Rabies Branch\nACIP meeting\nOct 24, 2024\n2Clade I MPXV: \nCountries \nknown for \ndecades to be \nendemicDemocratic Republic of the Congo (DRC), Central \nAfrican Republic, Republic of Congo, Cameroon, \nGabon\n•Exposure to infected wildlife\n•Person -to-person spread\n-Skin-to-skin contact (including intimate or sexual contact)\n-Direct contact with respiratory secretions (e.g., via kissing)\n-Direct contact with contaminated objects (e.g., shared towels, bedding)Monkeypox virus (MPXV) Transmission\nClade I Outbreak in DRC, 2023 -present\n•Reason for concern\n▪High number of suspect cases\n▪Laboratory confirmed cases identified in \nprovinces previously without cases\n•At least two concurrent outbreaks \n▪Clade Ia (e.g., Equateur Provence in western \nDRC): Mortality rate historically reported as \n1.4-11%; however, NIH trial in DRC indicates \nroutine supportive care led to mortality rate \nof ~1.7%* \n▪Clade Ib (e.g., Sud Kivu in eastern DRC): Seems \nto cause less severe disease than clade Ia; \nmortality rate <1% in DRC\n*https://www.nih.gov/news -events/news -releases/antiviral -tecovirimat -safe-\ndid-not-improve -clade -i-mpox -resolution -democratic -republic -congohttps://www.who.int/emergencies/disease -outbreak -\nnews/item/2024 -DON522\n\n•Clade Ia: multifactorial\n-From animals to people: high proportion of cases in children\n-Human -to-human spread in households: both adults and children\n-Sexual contact, regardless of sexual orientation and gender identity: adults\n•Clade Ib: Sexual contact comprises large proportionHow Clade I Mpox is Spreading in DRC*\n*Based on what is known at this time\nCases Outside of DRC\n•Clade Ia: Only detected in \nendemic countries (Central \nAfrican Republic and Republic of \nthe Congo)\n•Clade Ib: \n▪Associated with sustained \nspread: Burundi, Uganda, \nRwanda\n▪Not associated with sustained \nspread: Kenya, Thailand, Sweden, \nIndia, Germany\nhttps://wwwnc.cdc.gov/travel/notices/level2/mpox -drc-neighboring -countriesList of countries with sustained spread maintained here: \nhttps://www.cdc.gov/mpox/vaccines/index.html https://emergency.cdc.han/2024/han00513.asp\n•Primarily via sex (e.g., transactional sex) while visiting countries with sustained \ntransmission \n•Secondary spread\n-Limited (if any) in several non -endemic countries (e.g., Thailand, Sweden, India)\n-Uncertain at this time in some countries but believed to be associated with close \nhousehold contactHow Clade I Mpox is Spreading to Non -\nEndemic Countries*\n*Based on what is known at this time\nLaboratory Confirmed Clade I Mpox \nCases During 2024 (As of 13 October)\n*Only ~20% of suspected cases are laboratory confirmed; total DRC population = >110 million people\n†Many are cases among children; no deaths\n§Death in an individual with underlying health conditions and may not be due to mpox\nhttps://worldhealthorg.shinyapps.io/mpx_global/#24_Data_by_countryCountry Total casesCase \nfatality \nratio (%)Cases in \n2024Deaths \nin 2024Cases in the \npast six \nweeks1Deaths \nin the \npast six \nweeks1Clades \ndetected in \ncountryDate of last \nreported \ncase\nThe Democratic \nRepublic of the Congo8,207* 0% 6,962 25 1914 0 Clades Ia and Ib 13-Oct-24\nCentral African Republic 104 2% 57 1 10 0 Clade Ia 29-Sep-24\nRepublic of Congo 48 4% 22 0 1 0 Clade Ia 29-Sep-24\nBurundi 1,169 0% 1,169 0† 841 0 Clade Ib 13-Oct-24\nUganda 91 0% 91 0 76 0 Clade Ib 13-Oct-24\nKenya 13 8% 13 1§ 9 1 Clade Ib 13-Oct-24\nRwanda 6 0% 6 0 2 0 Clade Ib 15-Sep-24\n9Clade I Mpox Cases and the United States\nNo Clade I Cases in the United States*\n*Active surveillance conducted via clade -specific testing of high proportion of MPXV positive specimens, including those tested in commercial laboratories\n•Pre-travel counseling about risk reduction strategies \n-Avoid close contact with people sick with signs and symptoms of mpox, including \nskin or genital lesions\n-Avoid contact with contaminated materials used by people who are sick (e.g., \nclothing, bedding)\n•Vaccination, irrespective of sexual orientation and gender identity, for \ntravelers to certain countries* who  anticipate any of the following during \ntravel\n-Sex with a new partner\n-Sex at a commercial sex venue (such as a sex club or bathhouse)\n-Sex in exchange for money, goods, or other trade\n-Sex in association with a large public event (such as a rave, party, or festival)Risk Considered Low for U.S. Travelers\n*List of countries maintained here: https://www.cdc.gov/mpox/outbreaks/2023/index.html https://emergency.cdc.gov/han/2024/han00516.asp\n•Even in extreme scenario (e.g., household secondary attack risk of 30%, \ndouble the previously considered worse case scenario)†\n-Most simulated outbreaks were small (66% had ≤ 5 cases and 73% had ≤10 cases)\n-Most simulated outbreaks had minimal spread between households (72% \naffected ≤ 3 households)\n•Modeling suggests that even with extremely high secondary attack risk, \nhousehold clusters (including cases in children) would most likely involve 10 \nor fewer MPXV clade I cases, with limited spread between households \n•Based on what we know today and current characteristics of viral spread, \ndo not expect children to be heavily impacted if clade I diagnosed \ndomestically §Risk Considered Low for General U.S. \nPopulation*\n*https://www.cdc.gov/cfa -qualitative -assessments/php/data -research/mpox -risk-assessment/index.html\n† https://www.cdc.gov/cfa -modeling -and-forecasting/mpox -transmission -technical -brief/index.html and unpublished data\n§ https://www.cdc.gov/mpox/php/data -research/clade -i-mpox -in-children -in-africa -and-potential -impacts -on-children -in-the-\nunited -states.html\n13What CDC and Other U.S. Government \nPartners are Doing\n•Providing technical assistance and funding to DRC’s Ministry of Health\n• Working with USAID, WHO, International Organization for Migration, \nAfrican Field Epidemiology Network, and other partner teams on the \nground to help manage outbreaks\n•Collaborating with public health officials in several countries bordering DRC \nto assess needs and provide support for outbreak preparedness\n•Donating 1 million doses of JYNNEOS vaccine and $500 million for supportInternationally\n•Increasing capacity to rapidly detect, contain, and manage clade I cases \nshould they occur domestically\n•Increasing capacity to detect cases of clade I and clade II mpox through \nexisting surveillance systems, including wastewater testing in communities \nacross the United States and in select airports\n•Coordinating with state, tribal, local, and territorial public health \ndepartments to provide clinical, diagnostic, and other guidance\n•Raising awareness: Regular communications and updatesDomestically \n* https://www.cdc.gov/nwss/wastewater -surveillance/mpox -data.html\n•High number of suspected clade I mpox cases in DRC; ~20% are laboratory -\nconfirmed\n•Travel -associated spread of clade Ib to some countries\n-Cases milder than those associated with clade Ia \n-Predominantly associated with sex (e.g., transactional sex) with subsequent \nspread to others (e.g., children) likely via household contact\n•Risk to U.S. travelers low but counseling and vaccination should be provided \nto travelers\n•Impact to persons in the United States (including children) expected to be \nlow Summary*\n*Conclusions are based on investigations and other data available to CDC at the time this presentation was given; \nfindings and CDC guidance may change over time\n17ACIP\n•Reforming\n-Dr. Bonnie Maldonado, Workgroup chair\n-Dr. Faisal Minhaj:  Workgroup lead\n•Workgroup charge\n-Review NIH study about use of JYNNEOS in persons 12 -17 years of age\n-Consider bringing to an ACIP vote, use of JYNNEOS in persons 12 -17 years of age \nat risk for mpox during mpox outbreaks (including the global clade IIb outbreak)\n•Anticipating presentations (including Terms of Reference) during February \n2025 ACIP meeting\n•Planning publication of ACIP recommendations for persons 12 years of age \nand older in one consolidated MMWRWorkgroup \nThe findings and conclusions in this report are those of the authors and do not \nnecessarily represent the official position of the Centers for Disease Control and \nPreventionThank you\n19\npoxvirus@cdc.gov", "summary": "Clade I Mpox Outbreak:   Situational UpdateCenters for Disease Control and Prevention Agam Rao, MD CAPT, U.S. Public Health Service Chief Medical Officer, Poxvirus and Rabies Branch ACIP meeting Oct 24, 2024 2Clade I MPXV:  Countries  known for  decades to be  endemicDemocratic Republic of the Congo (DRC), Central  African Republic, Republic of Congo, Cameroon,  Gabon •Exposure to infected wildlife •Person -to-person spread -Skin-to-skin contact (including intimate or sexual contact) -Direct…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-23-24-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-10-23-24/01-MPOX-Rao-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 19}
{"title": "01 RSV Adult Kotton 508", "content": "1\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nAdult Respiratory Syncytial Virus (RSV) Session\nCamille Kotton, MD \nChair, Adult RSV Work Group\nAdvisory Committee on Immunization Practices (ACIP) \nJune 26, 2024\n2Adult RSV Work Group Membership \nACIP Voting Members\nCamille Kotton (Chair)\nKeipp  Talbot \nSarah Long\nAlbert Shaw\nEx Officio Members\nRachel Zhang (FDA) \nNicholas Geagan (FDA)\nNadine Peart Akindele (FDA) \nSonnie Kim (NIH/NIAID)\nMichelle Juaneza (HRSA)\nUzo Chukwuma (IHS)CDC Co -Leads\nMichael Melgar \nAmadea BrittonConsultants\nRobert Atmar (Baylor College of \nMedicine)\nDoug Campos -Outcalt (University of \nArizona)\nHelen Chu (University of Washington)\nPeter Donofrio (Vanderbilt University)\nMarie Griffin (Vanderbilt University)\nRebecca Morgan (Case Western Reserve \nUniversity)\nCynthia Lucero -Obusan  (Veterans Health \nAdministration)\nTracy Ruckwardt (NIH/NIAID)\nJonathan Temte  (University of Wisconsin)Liaisons\nKenneth Schmader (AGS)\nVidya Sundareshan (ACP)\nGretchen LaSalle (AAFP)\nApril Killikelly (NACI, PHAC)\nWinnie Siu (NACI, PHAC)\nKatherine Williams (APTR) \nRuth Lynfield (NFID) \nBindy Crouch (AIM) \nSteven Pergam (IDSA)\nElizabeth Skoy ( APhA )\n3▪Dr. Albert Shaw will be the incoming work group chair for the adult RSV work group \nstarting in July 2024. Transition in Work Group Chair\n4Melissa Coughlin\nFatima Dawood\nKatherine Fleming -Dutra\nKristen Folsom\nJarrett Gartin\nMonica Godfrey\nAron Hall\nFiona Havers\nMichele Hlavsa\nJefferson Jones\nRuth Link -Gelles\nAgustin Lopez\nJosephine Mak\nMeredith McMorrow\nNoelle -Angelique MolinariDanielle Moulia\nIsmael Ortega -Sanchez\nLakshmi Panagiotakopoulos\nPragna Patel\nMonica Patton\nAmanda Payne\nDerrell Powers\nMila Prill\nLauren Roper\nDiya Surie\nNatalie Thornburg\nRaigan Wheeler\nMegan Wallace\nTrang WisardCDC Contributors\nImmunization Safety Office\nAnne Hause\nPedro Moro\nChristine Olson\nDavid Shay\nKaren Broder\nJohn Su\nEric Weintraub\nMichael McNeil\nJulianne GeeImmunization Services Division\nCarla Black\nKayla Calhoun \nJennifer Kriss \nJames Singleton\nNicole Dowling\nAndrew Leidner\nJamison Pike\nJames Singleton\nPatricia Wodi\nInfluenza Division\nJill Ferdinands\nLisa GrohskopfNCIRD Office of the Director\nHannah Rosenblum\nMelinda Wharton\nJessica MacNeilCoronavirus and Other Respiratory Viruses Division \n5▪ACIP voted on this recommendation at the June 2023 meeting\n▪Recommendation is not product -specific; administer whichever vaccine is availableCDC and ACIP currently recommend that adults aged 60 \nyears and older may receive a single dose of RSV \nvaccination, using shared clinical decision -making.\nhttps://www.cdc.gov/mmwr/volumes/72/wr/mm7229a4.htm  \n6▪Moderna presented safety and efficacy data from the first 9 months of follow up in their phase 3 \ntrial in adults aged ≥60 years\n▪CDC presented risk -stratified rates of RSV -associated hospitalization in U.S. adults aged 50 \nyears and older\n▪CDC gave an update on uptake and implementation of RSV vaccine in U.S. adults aged 60 years \nand older during the first season following the recommendation\n▪CDC and FDA presented on post -marketing safety of the protein subunit RSV vaccines (GSK’s \nAREXVY and Pfizer’s ABRYSVO) in adults aged 60 years and older\n▪CDC presented an analysis comparing the estimated magnitude of public health benefit and \npotential risk of Guillain -Barre syndrome (GBS) associated with protein subunit RSV vaccination \nin adults aged 60 years and older\n▪For adults aged 60 years and older who remain unvaccinated, ACIP agreed with encouraging \ntiming of RSV vaccination in the late summer and early fall to optimize public health benefitsRecap of Adult RSV session, February 2023\n7▪Moderna mRESVIA  for use in adults aged 60 years and older (received FDA approval \nMay 31, 2024)\n▪GSK AREXVY for use in adults aged 50 -59 years at increased risk of severe RSV disease \n(received FDA approval June 7, 2024)\n▪Continued discussion of safety, including risk of GBS, following RSV vaccination\n▪Shift from a shared clinical decision -making recommendation to:\n–Potential universal recommendation in adults 75 and older\n–Potential risk -based recommendation in adults 60 –74\n–Potential risk -based recommendation in adults 50 –59Recent work group discussion\n8▪In June 2023, ACIP recommended RSV vaccination in adults 60 and older using shared \nclinical decision -making\n–In addition to benefits of vaccination, the shared clinical decision -making discussion, as intended by ACIP , is also \nmeant to include discussion of the potential risk of vaccine -associated adverse events associated with RSV \nvaccine, specifically Guillain Barre Syndrome.\n▪In the first year following this recommendation, we have learned:\n–Feedback from healthcare providers that having SCDM conversations is not simple in practice.\n–Unlike a universal recommendation where there’s a clear call to action to vaccinate, with SCDM the call to action \nis to discuss with a healthcare provider, a less clear message.\n▪A risk -based recommendation for adults 60 –74 and a universal recommendation for \nadults ≥75 years would potentially highlight more clearly for providers and other public \nhealth officials which adults are likely to benefit from an RSV vaccine and provide a \nclearer recommendation for patients. Re-evaluating Shared Clinical Decision -Making (SCDM) \nrecommendation\n9▪Dr. Iona Munjal (Pfizer) \n▪Dr. Susan Gerber (GSK) \n▪Dr. Rituparna Das (Moderna) \n▪Dr. James Donahue (Marshfield Clinic Research Institute)\n▪Dr. Patricia Lloyd (FDA)\n▪Dr. Diya Surie (CDC, NCIRD)\n▪Dr. David Hutton (University of Michigan)\n▪Dr. David Hutton (University of Michigan)\n▪Dr. Ismael Ortega -Sanchez (CDC/NCIRD)\n▪Dr. Michael Melgar (CDC/NCIRD), Lauren \nRoper (CDC/NCIRD), Dr. Amadea Britton (CDC/NCIRD)\n▪Dr. Michael Melgar (CDC/NCIRD)Agenda: Wednesday June 26, 2024\n▪Manufacturer presentation: ABRYSVO (Pfizer) safety and \nimmunogenicity in non -pregnant adults aged 18 -59 years \n▪Manufacturer presentation: AREXVY (GSK) immunogenicity \nwith a 24 -month revaccination interval \n▪Manufacturer presentation: mRESVIA  (Moderna) season 2 \nsafety and efficacy update\n▪Postmarketing  safety updates: Vaccine Safety Datalink \n▪Evaluation of Guillain -Barre Syndrome (GBS) following RSV \nvaccination among adults 65 years and older\n▪Observational RSV vaccine effectiveness\n▪Economic analysis of adult RSV vaccination\n▪Update to benefits and risks discussion\n▪Comparison of economic analyses of adult RSV vaccination\n▪Evidence to Recommendations\n▪Clinical Considerations\n10\nFor more information, contact CDC\n1-800 -CDC -INFO (232 -4636)\nTTY:  1 -888 -232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention.\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.", "summary": "1 Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. Adult Respiratory Syncytial Virus (RSV) Session Camille Kotton, MD  Chair, Adult RSV Work Group Advisory Committee on Immunization Practices (ACIP)  June 26, 2024…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/01-RSV-Adult-Kotton-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 10}
{"title": "02 RSV Adult Munjal 508", "content": "RSVpreF Adult Clinical \nDevelopment Update\nACIP Meeting 26 June 2024Iona Munjal, MD\n2Extending Adult IndicationBivalent Stabilized Prefusion F\n•Based on contemporary RSV A & RSV B strainsRSVpreF Adult Clinical Development Program Updates\nABRYSVO®\n(Respiratory Syncytial Virus Vaccine)\n•≥60 years (RENOIR trial) Season 2 analyses\n•≥18 years at High Risk for RSV ( MONeT  trial) \n•Real-world effectiveness dataAdditional Clinical Trial Data\nIndication for ABRYSVO\nMaternal\nImmunize pregnant women \nto prevent RSV -associated \nlower respiratory tract \ndisease (LRTD) in infants \nfrom birth through 6 months \nof ageOlder Adult \nActive immunization \nto prevent \nRSV-associated \nLRTD in adults \n≥ 60 years of ageApplication Submitted for FDA Review\nActive immunization to prevent\nRSV-associated LRTD in adults\n18-59 years of age\n\n3Updated Data on RENOIR, Real -World Evidence, and MONeTRSVpreF Adult – Clinical Development Program\n•Revaccination \nY1 and Y2•Revaccination \nY3 and Y4•Adults 18 -59 \nwith chronic \nmedical \nconditions •Adults ≥ 18 with \nimmuno - \ncompromising \nconditions Adults ≥ 60 Adults 18 –59 Adults ≥ 18 Adults ≥ 65 Adults ≥ 65RENOIR MONeT COVID COAD FLU COAD REAL -WORLDAdults ≥ 18 Older Adults ≥ 60 \n•Efficacy \nthrough 2 \nseasonsAdults ≥ 60\n•KPSC \nObservational \nRetrospective \nCase Control \nStudy•Non-inferiority \ndemonstrated•Non-inferiority \ndemonstrated\nOngoing Ongoing Ongoing Ongoing\nKPSC, Kaiser Permanente Southern California\n4Unsolicited AEs\nSAEs, NDCMCsLocal Reactions\nSystemic EventsStart Season 1 (2021) End Season 1 Start Season 2 End Season 2 (2023)\nTheRSV Vaccine Efficacy Study iNOlder Adults\nImmunized Against RSV Disease\nStudy Start End of S1 Analysis\n(Northern and Southern Hemisphere) Mid-Season 2 Analysis  \n(Northern Hemisphere)\nWeekly active surveillance for acute respiratory symptomsePrimary Analysis End of S2 Analysis\n(Northern and \nSouthern \nHemisphere) \n16.4 months  7.1  months 7.6  monthsSafety \nSurveillance\nAverage \nTime Since\nVaccination Weekly active surveillance for acute respiratory symptomse\nRSV, respiratory syncytial virus; RSVpreF, respiratory syncytial virus prefusion F subunit, AE, adverse event; NDCMC, newly d iagnosed chronic medical condition; \nSAE, serious adverse event.38,863  participants / Adults  ≥60 years \n5LRTD = lower respiratory tract disease\n1. Eiras D. 2024 (May 17 -22). ATS  2. Walsh EE, et al. N. Engl J Med . 2023:338:1465 -1477.RSVPreF  Maintained High Efficacy in Season 2\nVE Against RSV -associated LRTD in Subjects with ≥3 New or Worsened Lower Respiratory Symptoms (95% CI)1,2\n40%50%60%70%80%90%100%\nSeason 1 Season 2 Across 2 SeasonsSeason 1 Season 20%88.9% (53.6, 98.7)\n77.8% (51.4, 91.1)81.5% (63.3, 91.6)Primary endpoint: \nRSV-LRTD with ≥3 symptoms\n6.Consistent Efficacy was Observed Across RSV Overall and by \nSubgroups A and B \nRSV-LRTI with ≥ 3 SymptomsNumber of Events1Vaccine Efficacy\n(95% CI) RSVPreF Placebo\nOverallSeason 1 2 18 88.9% (53.6, 98.7)\nSeason 2 8 36 77.8% (51.4, 91.1)\nAcross 2 Seasons 10 54 81.5% (63.3, 91.6)\nRSV-ASeason 1 1 5 80.0% (-78.7, 99.6)\nSeason 2 5 26 80.8% (49.1, 94.2)\nAcross 2 Seasons 6 31 80.6% (52.9, 93.4)\nRSV-BSeason 1 1 12 91.7% (43.7, 99.8)\nSeason 2 2 10 80.0% (6.1, 97.9)\nAcross 2 Seasons 3 22 86.4%  (54.6, 97.4)\n-20 0 20 40 60 80 100\nVaccine Efficacy (%, 95% CI)Primary endpoint: \nRSV-LRTD with ≥3 symptoms\n1. Represents LRTD (lower respiratory tract disease) events. One S1 case and one S2 case (both in the placebo group) and one S2 case in RSVPreF  group were based on local testing without RSV subgroup. One S2 case in placebo group had \nboth A and B subgroups; \nNotes: RSV, respiratory syncytial virus; VE, vaccine efficacy\n7Updated Data on RENOIR, Real -World Evidence, and MONeTRSVpreF Adult – Clinical Development Program\n•Revaccination \nY1 and Y2•Revaccination \nY3 and Y4•Adults 18 -59 \nwith chronic \nmedical \nconditions •Adults ≥ 18 with \nimmuno - \ncompromising \nconditions Adults ≥ 60 Adults 18 –59 Adults ≥ 18 Adults ≥ 65 Adults ≥ 65RENOIR MONeT COVID COAD FLU COAD REAL -WORLDAdults ≥ 18 Older Adults ≥ 60 \n•Efficacy \nthrough 2 \nseasonsAdults ≥ 60\n•KPSC \nObservational \nRetrospective \nCase Control \nStudy•Non-inferiority \ndemonstrated•Non-inferiority \ndemonstrated\nOngoing Ongoing Ongoing Ongoing\n8Abrysvo\nUnvaccinated\nAbrysvo\nUnvaccinatedCASES\nRSV +\nCONTROLS\nRSV -Study\nEvents\nwith Test\nResultsSOURCE POPULATION\nAdults ≥60 years \nHospitalized or with \nEmergency Department Visit\nfor Lower Respiratory Tract \nDisease\n•Large healthcare network  with high -risk population: Kaiser Permanente Southern California (KPSC)\n•↑ RSV testing by salvaging NP/nasal swabs collected for other respiratory pathogen testing\n•VE against RSV -related LRTD hospitalization/ED visits calculated using multivariable logistic regression\n•Primary analysis controls: RSV -, hMPV -, influenza -, SARS -CoV-2-, and non -vaccine -preventable disease pathogen+\n•Sensitivity analysis with all RSV negative as controlsLeveraging KPSC  High -quality Real -World Data PlatformKaiser Permanente Southern California Real -World Data: Observational \nRetrospective Test Negative Design Case Control Vaccine Effectiveness Study\nFigure adapted from: Fukushima et al  (2017) Basic principles of test -negative design in evaluating influenza vaccine effectiven ess\nARI, acute respiratory illness; ED, emergency department; hMPV, human metapneumovirus; LRTD  , lower respiratory tract disease; NP, nasopharyngeal; RSV, respiratory syncytial virus; VE, vaccine efficacy; VPD , vaccine preventable disease\n9Early Real -World Data Reinforces VE among Persons at Highest Risk of Severe \nRSV Disease: 89% -- Similar to Randomized Clinical Trial VE Results\na Pre-specified primary analysis controls test negative for RSV, flu and SARS -CoV2  and test positive for a non -vaccine preventable disease in the primary analysis. A sensitivity analysis includes a broader cont rol group definition which is all \nwho test negative for RSV. b Adjusted for age, sex, encounter months, race/ethnicity, Charlson  index, previous outpatient encounters, previous inpatient encounters, previous ED encounters, COPD, diabetes, renal disease, and peripheral \nvascular disease. c Patient 1: 93 years old, Charlson  index of 6; Patient 2: 63 years old, Charlson  index of 4. Vaccine Effectiveness against RSV -related LRTD hospitalization or ED visit\nTest Negative Controlsa\nN (%)Test Positive Cases\nN (%) Crude\nVE (95%CI)Adjusted VEb\n(95% CI) Unvaccinated, \nn (%)Vaccinated, \nn (%)Unvaccinated, \nn (%)Vaccinated, \nn (%)\nPrimary Analysisa\n(n=1336)734 (96.6%) 26 (3.4%) 574 (99.7%) 2c(0.3%)90%\n(58–98)89%\n(52–97)\n•Study population description\n•57% of study population was over 75 years of age\n•93% ≥1 Charlson  comorbidity\n•14% immunocompromised\n•Primary analysis VE= 89% (95% CI: 52 –97) (Table)\n•Sensitivity Analysis (controls with any RSV negative) VE = 89% (95% CI: 54 –97)\n•Study extension planned to provide Abrysvo VE for specific population subgroups (e.g., by age, high -risk conditions) and seasons  2, 3, and beyondResults\n10Updated Data on RENOIR, Real -World Evidence, and MONeTRSVpreF Adult – Clinical Development Program\n•Revaccination \nY1 and Y2•Revaccination \nY3 and Y4•Adults 18 -59 \nwith chronic \nmedical \nconditions •Adults ≥ 18 with \nimmuno - \ncompromising \nconditions Adults ≥ 60 Adults 18 –59 Adults ≥ 18 Adults ≥ 65 Adults ≥ 65RENOIR MONeT COVID COAD FLU COAD REAL -WORLDAdults ≥ 18 Older Adults ≥ 60 \n•Efficacy \nthrough 2 \nseasonsAdults ≥ 60\n•KPSC \nObservational \nRetrospective \nCase Control \nStudy•Non-inferiority \ndemonstrated•Non-inferiority \ndemonstrated\nOngoing Ongoing Ongoing Ongoing\n11Licensure in 18 –59 Years of Age Will Be Based on Satisfactory Safety and Immunogenicity \nCompared to RSVPreF  in Adults ≥ 60 YearsSafety in Adults 18 –59 Years Has Been Demonstrated in 7 Clinical Studies\nTotality of Safety Data to Support Licensure in Adults ≥18 to 59 Years \n] Study 1001 (n=98): Phase 1/2 Dose Ranging\nHuman Challenge  (n=35): Safety and Efficacy of 120μg without Adjuvant\nStudy 1014 (n=745): Lot Consistency\nStudy 1004 (n=282): Non-pregnant Concomitant Tdap\nStudy 1003 (n=115): Pregnant Women, Safety, Early Efficacy\nStudy 1008 (n=3689): Pregnant Women, Safety, Pivotal Efficacy\nStudy 1023 (n=453): (MONeT ) Immunogenicity & Safety1\n>5,400 Adults Aged 18 -59 Years of Age 2\n3\n4\n5\n6\n7\n\n12Phase 3 Study Design MONeT   Substudy  A (Chronic Conditions)RSVPreF  in Adults ≥18 to 59 Years of Age at High Risk of \nSevere RSV Disease\nAdults ≥18 to 59 Years of Age  N = 675 Day 1 Month 1 Month 6\nVaccination 1 Follow -Up Follow -Up\nBlood draw and vaccination Blood draw\nReactogenicity e -diary\nAEs\nAESIs, SAEs, NDCMCs\n2:1RSVPreF 120 µg\nPlacebo\ne\nRENOIR Adults ≥60 Years of Age Pre-vaccination 1 Month Post -Vaccination\nBridged Immunogenicity \nto RENOIRBlood draw Blood draw\n Historical cohort\n1. Clinicaltrials.gov NCT05842967  2. Pfizer Data on File\n13RSVPreF \n120 µg\n(N = 453) ; \nn (%)Placebo\n(N = 225) ; \nn (%)Total\n(N = 678) ; \nn (%)\nSex\nMale 193 (42.6) 73 (32.4) 266 (39.2)\nFemale 260 (57.4) 152 (67.6) 412 (60.8)\nRace\nWhite 312 (68.9) 152 (67.6) 464 (68.4)\nBlack or African American 106 (23.4) 57 (25.3) 163 (24.0)\nAsian 24 (5.3) 9 (4.0) 33 (4.9)\nEthnicity\nHispanic/Latino 102 (22.5) 48 (21.3) 150 (22.1)\nNon-Hispanic/non -Latino 348 (76.8) 175 (77.8) 523 (77.1)\nAge at Vaccination\n18-49 Years 240 (53.0) 113 (50.2) 353 (52.1)\n50-59 Years 213 (47.0) 112 (49.8) 325 (47.9)\nMean (SD) 46.8 (9.9) 46.4 (10.5) 46.7 (10.1)\n* Participants with multiple comorbidities are represented more than onceDemographics Between Vaccine and Placebo Recipients \nRSVPreF \n120 µg\n(N = 453) ; \nn (%)Placebo\n(N = 225) ; \nn (%)Total\n(N = 678) ; \nn (%)\nWith At Least 1 Prespecified \nMedical Condition*453 (100.0) 223 (99.1) 676 (99.7)\nChronic Pulmonary \nConditions239 (52.8) 116 (51.6) 355 (52.4)\nCOPD 25 (5.5) 11 (4.9) 36 (5.3)\nAsthma 198 (43.7) 88 (39.1) 286 (42.2)\nCardiovascular Conditions 38 (8.4) 16 (7.1) 54 (8.0)\nCHF 9 (2.0) 3 (1.3) 12 (1.8)\nCAD 19 (4.2) 4 (1.8) 23 (3.4)\nDiabetes 189 (41.7) 101 (44.9) 290 (42.8)\nOther 139 (30.7) 68 (30.2) 207 (30.5)\nLiver Disease 20 (4.4) 13 (5.8) 33 (4.9)\nRenal Disease 17 (3.8) 4 (1.8) 21 (3.1)\nNeurologic Disease 16 (3.5) 1 (0.4) 17 (2.5)\nTobacco Use \nCurrent Tobacco Use 78 (17.2) 39 (17.3) 117 (17.3)\n1. Clinicaltrials.gov NCT05842967  2. Pfizer Data on File\n14Local Reactions\nMedian Time to Resolution: 1 –2 days\n36.6%\n11.6%35.3%\n10.7%\n6.0%\n0.4%7.1%\n0.9%\n0102030405060708090100\nRSVpreF\n120µg\nPlacebo\nRSVpreF\n120µg\nPlacebo\nRSVpreF\n120µg\nPlacebo\nRSVpreF\n120µg\nPlaceboPain at\nInjection \nSite1Redness2Swelling2Any\n1. Severity definition: mild = no interference with daily activity; moderate = some \ninterference with daily activity; severe = prevents daily activity \n2. Severity definition: mild = >2 -5 cm, moderate = >5 -10 cm; severe = >10 cm \nRSVPreF N = 451; placebo N = 225Solicited Local/Systemic Reactions & Systemic Events Were \nMild to Moderate and Resolved Quickly in Participants 18 –59 Years\nSystemic Events\nMedian Time to Resolution: 1 –2 days\n1. Severity definition: mild = no interference with daily activity; moderate = some interference with daily activity; severe = prevents daily activity\n2. Severity definition: mild = 2 -3 loose stools in 24h; moderate = 4 -5 loose stools in 24h; severe = 6 or more loose stools in 2 4h\n3. Severity definition: mild 38.0 °C-38.4 °C; moderate >38.4 °C-38.9 °C; severe >38.9 °C-40.0 °C; grade 4 >40.0 °C\n4. Severity definition: mild = 1 -2 time(s) in 24h; moderate = >2 times in 24h; severe = requires intravenous hydration\nRSVPreF N = 451: Placebo N = 22557.4%55.6%\n37.3% 38.2%\n28.4%30.2%\n24.4%\n16.0% 14.9%16.9%\n12.4%10.2%11.8%10.2%\n2.0% 1.3% 1.6% 1.3%RSVpreF\n120µg\nPlacebo\nRSVpreF\n120µg\nPlacebo\nRSVpreF\n120µg\nPlacebo\nRSVpreF\n120µg\nPlacebo\nRSVpreF\n120µg\nPlacebo\nRSVpreF\n120µg\nPlacebo\nRSVpreF\n120µg\nPlacebo\nRSVpreF\n120µg\nPlacebo\nRSVpreF\n120µg\nPlaceboFatigue1Headache1Muscle \nPain1Any Joint Pain1Nausea1Vomiting4Diarrhea2Fever3\n Mild Moderate Severe\n1. Clinicaltrials.gov NCT05842967  2. Pfizer Data on File\n15*Related event was urticaria Grade 1 on the day of vaccination that resolved without treatment or medical attention;\nAbbreviations: AE, adverse event; NDCMC, newly diagnosed chronic medical condition; SAE, serious adverse event.Adverse Events Comparable Between Vaccine and Placebo Groups\nAdverse Event CategoryRSVPreF 120 µg\n(N = 453) ; n (%)Placebo\n(N = 225) ; n (%)\nFrom Vaccination Through 1 -Month Follow -Up Visit \n​Any Event 31 (6.8) 17 (7.6)\n​Related*1 (0.2) 0\n​Severe 1 (0.2) 4 (1.8)\nFrom Vaccination Throughout the Study\nSAE 5 (1.1) 7 (3.1)\nRelated SAE 0 0\nAE Leading to Withdrawal 1 (0.2) 1 (0.4)\nAE Leading to Death 1 (0.2) 0\nAE of Special Interest \n     (includes GBS and atrial fibrillation)0 0\n1. Clinicaltrials.gov NCT05842967  2. Pfizer Data on File\n16Seroresponse Rate RSV A & B (Comparison: 18 –59y High Risk to ≥60y) SRR Difference* (95% CI)\nSRR Difference RSV -A 5.1 (1.2, 9.2)\nSRR Difference RSV -B 8.3 (4.2,12.6)\nAbbreviations: GMR = geometric mean ratio; SRR=seroresponse rate \n*Analysis of covariance model used as per protocol with sex and baseline titer (in logarithm scale) adjustedNon-Inferiority Met for All Four Co -Primary Endpoints\nGMR RSV A & B  (Comparison: 18 –59y High Risk to ≥60y) GMR (95% CI)\nModel Adjusted* GMR RSV -A 1.57 (1.396, 1.759)\nModel Adjusted* GMR RSV -B 1.52 (1.333, 1.725)\n0.667 1.0 1.5 2.0\nGMT Ratio\n-10.0 0.0 10.0\nSRR Differences (%)Both Primary Endpoints Met Non -inferiority (CI LB >0.667)\nBoth Primary Endpoints Met Non -inferiority (CI LB > -10%)\n1. Clinicaltrials.gov NCT05842967  2. Pfizer Data on File\n17RENOIR study has shown duration of protection is at least 2 years with high efficacy in season 2\nRSVPreF  Addresses a Significant Burden in Adults and Those With Chronic ConditionsSummary of Clinical Development Updates of RSVPreF in Adults\nRSVpreF in adults 18 –59 years of age ( MONeT  study) demonstrated robust RSV -A and RSV -B subgroup \nneutralizing responses that met NI to the RENOIR study, where safety and efficacy were demonstrated\nRSVPreF  is currently under review by the FDA for use in adults 18 -59 years of agePreliminary real -world observational data supports RCT efficacy in older population, largely with \ncomorbidities", "summary": "RSVpreF Adult Clinical  Development Update ACIP Meeting 26 June 2024Iona Munjal, MD 2Extending Adult IndicationBivalent Stabilized Prefusion F •Based on contemporary RSV A & RSV B strainsRSVpreF Adult Clinical Development Program Updates ABRYSVO® (Respiratory Syncytial Virus Vaccine) •≥60 years (RENOIR trial) Season 2 analyses •≥18 years at High Risk for RSV ( MONeT  trial)  •Real-world effectiveness dataAdditional Clinical Trial Data Indication for ABRYSVO Maternal Immunize pregnant women  to…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/02-RSV-Adult-Munjal-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 17}
{"title": "03 RSV Adult Gerber 508", "content": "CO-1\nAREXVY (Adjuvanted RSVPreF3) \n2-Year Update\nACIP June 26, 2024\nSusan Gerber, MD\nMedical Director \nGSK\nPresentation by GSK at ACIP June 26, 2024\nCO-2\nAREXVY Indications \nAREXVY now indicated for active immunization for prevention of lower \nrespiratory tract disease (LRTD) caused by RSV in\n▪Individuals ≥ 60 YOA\n▪Individuals 50-59 YOA at increased risk for LRTD caused by RSV\nYOA: years of age\nFDA, 2024. AREXVY Prescribing Information (PI); https://www.fda.gov/media/167805/download (URL accessed June 2024)\nCO-3\nRisk Factors for Severe RSV Disease Are Highly Prevalent Among \nAdults ≥ 50 Years with Disparities Observed by Race and Ethnicity\n▪31.4%  of adults 50–59 YOA and 46.9%  of adults ≥ 60 YOA are diagnosed with ≥ 1 risk factor for severe RSV diseasea\n▪Mexican American/other Hispanic and NH Black adults have significantly higher prevalence of ≥ 1 diagnosed risk factor in \neach of these age groups (vs. NH White adults)b\naSelf-reported diagnosis of the following conditions: CHF, CHD, stroke, angina pectoris, MI, COPD (COPD, emphysema, or current chro nic bronchitis), asthma (current), diabetes, liver disease (current), renal \ndisease. bOther  race/multi -racial results not presented. \n*Statistically significant based on two -sided P < 0.05. P -values were calculated based on pairwise chi -square analysis on 2x2 ta bles using non -Hispanic White adults as the reference group. \nNotes: Retrospective, cross -sectional analysis of pooled NHANES data spanning the period 2011 -March 2020 .Weighting to the United States population conducted in accordance with NHANES published \nguidelines: https://wwwn.cdc.gov/nchs/nhanes/tutorials/weighting.aspx . CHD, coronary heart disease; CHF, congestive heart failure; COPD, chronic obstructive pulmonary disease; MI, myocardial infar ction; \nNH, Non -Hispanic; NHANES, National Health and Nutrition Examination Survey; YOA, years of age.Horn et al. NFID ACVR, May 8 -10, 2024  31.4%46.9%\n29.9%44.9% 43.6%\n34.1%*36.9%*\n24.1%*50.4%*54.0%*\n29.9%44.9%\n34.1%*50.4%*\n36.9%*54.0%*\n24.1%*43.6%\n0%20%40%60%\n50-59 years ≥60 yearsPercentage of US adults with \n≥1 diagnosed risk factor for \nsevere RSV disease\nNH White Mexican American/other Hispanic NH Black NH Asian50–5 9 YOA ≥ 60 YOA% of \nUS adults with\n ≥ 1 diagnosed risk \nfactor for severe \nRSV disease\nCO-4\nAReSVi -004: Immunogenicity, Safety, Reactogenicity and \nPersistence of Single Dose of AREXVY Vaccine and \nDifferent Revaccination Schedules in Adults ≥ 60 YOA\nRandomized, open -label, multi -country study (NCT04732871)\nPresentation by GSK at ACIP June 26, 2024\nCO-5\nAReSVi-004 Phase 3 Study Design1-3\nTimepoint   \nHI only\n(n≈215)D1 M13 M24 M25 M60\nPresentation by GSK at ACIP June 26, 2024*RSV M24 revaccination: Participants receiving first dose (Dose 1) of AREXVY at Day 1 followed by revaccination dose at 24 months post Dose 1; **Primary endpoints: NAb\n(neutralizing antibody) geometric mean titers (RSV-A and RSV-B) at Day 1 (pre-vaccination), D31, M6, and M12 post-dose 1; ***CMI response in terms of frequency of RSVPreF3-\nspecific CD4+ and/or CD8+ T-cells expressing > 2 activation markers; CMI, cell-mediated immunity; HI, humoral immunity; 1. Schwarz TF et al. 2023; 2. ClinicalTrials.gov.\nNCT04732871; 3. GSK, 2024 https://www.gsk-studyregister.com/en/trial-details/?id=212496  (All URLs accessed June 2024)M12 M18 M30 M36 M37 M42 M48 M49 M54\nHI + CMI\n(n≈115)\nHI + CMI\n(n≈345)Safety\n (n≈645)\nRSV 1 Dose\nN≈330\nRSV Annual\nN≈9901st analysis 2nd analysis 3rd analysisAnalyses may be performed or \nregrouped depending on data availabilityFinal End \nof Study \nanalysis AREXVY\nBlood sample for HI responses\nBlood sample for CMI responses4th analysis\nR\n3:1:1Current analysis\nRe-randomization 1:1 (N≈ 330)\nHI only\n(n≈215)HI + CMI\n(n≈115)\nRSV M24 \nRevaccination*\nN≈330\nAll participants followed for safety\nPrimary objective: To evaluate humoral immune response following 1-dose primary schedule up to 12 months post-dose 1**\nKey secondary objectives: To evaluate humoral and CMI *** responses following 1-dose primary schedule and re-vaccination doses, up to study end (M60); \nsafety and reactogenicity also assessedAReSVi -004 \nCO-6\nPresentation by GSK at ACIP June 26, 2024AReSVi -004 \nGMT\n(ED60)\n[95%CI]\nM\n6M\n12M\n18M\n24M\n25M\n13100010000\nM\n6M\n12M\n18M\n24M\n25M\n13RSV Annual Revaccination RSV M24 Revaccination RSV 1 Dose\nTimepointD\n31D\n1100010000\nD\n31D\n1RSV-A Serum Neutralization Titers RSV-B Serum Neutralization TitersHigher RSV -A and RSV -B Neutralizing Antibody Titers \nObserved After 24 Month Vaccination Interval\nRSV Annual revaccination (N=250 -341): Participants receiving first dose (Dose 1) of AREXVY at Day 1, followed by revaccination d ose at 12 months post Dose 1 and at 24 months post Dose 1; \nRSV M24 revaccination (N= 223 -319): Participants receiving first dose (Dose 1) of AREXVY at Day 1 followed by revaccination dose  at 24 months post Dose 1; \nRSV 1 dose (N=281 -318): Participants receiving single dose (Dose 1) of AREXVY at Day 1; ED60: estimated dilution 60; GMT: geomet ric mean titer\nCO-7\nCD4+ T -Cell Responses Increased 1 -Month Post Each \nVaccination DoseAReSVi -004 \nPresentation by GSK at ACIP June 26, 2024RSVPreF3 CD4+ \nT-cells, /106 cells\n0500100015002000\n1 201 401 601 M\n6M\n12M\n18M\n24M\n25M\n13D\n31D\n1\nTimepointRSV Annual Revaccination RSV M24 Revaccination RSV 1 Dose\nRSV Annual  revaccination (N=216 -286): Participants receiving first dose (Dose 1) of AREXVY at Day 1, followed by revaccination dose at 12 months post Dose 1 and at 24 months post Dose 1; RSV \nM24 revaccination (N=68 -94): Participants receiving first dose (Dose 1) of AREXVY at Day 1 followed by revaccination dose at 24 months post Dose 1; RSV  1 dose (N=83 -95): \nParticipants receiving single dose (Dose 1) of AREXVY at Day 1; CD4+ T -cells expressing ≥ 2 activation markers including ≥ 1 cytokine among CD40L, 4 -1BB, IL -2, TNF -α, IFN -γ, IL-13, IL -17 \nevents/ 106 cells; (by intracellular staining)\nCO-8\nLower Prevaccination  RSV-A NAb Titers  Associated with Higher \nSeroresponse Rates (≥ 4 -Fold Increase) Following Revaccination\nn/N 22 / 67 4 / 67 6 / 67 3 / 67\nNAb baseline \nGMT (ED60)193 – <1,304 1,304 – <2,381 2,381 – <4,078 4,078 – 123,535Participants with \n≥ 4-fold increase \nin RSV- A NAb \ntiters at \nM13 vs M12\n[95% CI]\n29 / 55 23 / 56 10 / 56 7 / 56\n283 – <1,000 1,000 – <1,849 1,849 – <3,736 3,736 – 38,8400%20%40%60%80%100%\n0 1 2 3 432.8 \n(21.8, 45.4)\n6.0 \n(1.7, 14.6)9.0 \n(3.4, 18.5) 4.5 \n(0.9, 12.5)RSV Annual Revaccination\n1 2 3 4Participants with \n≥ 4-fold increase \nin RSV- A NAb \ntiters at \nM25 vs M24\n[95% CI]\n0%20%40%60%80%100%\n0 1 2 3 41 2 3 417.9 \n(8.9, 30.4) 12.5\n(5.2, 24.1)41.1 \n(28.1, 55.0)52.7 \n(38.8, 66.3)\nQuartile* Quartile*RSV M24 Revaccination\nPresentation by GSK at ACIP June 26, 2024*Participants were grouped into quartiles depending on their baseline NAb titers: 1 = baseline NAb min–<1; 2 = baseline NAb 1–<2 (median); 3 = baseline NAb 2 (median) –<3; \n4 = baseline NAb 3–4. Participants in the quartile 1 had the lowest pre -revaccination NAb and those in the quartile 4 had the highest; ED60, serum dilution inducing 60% inhibition in plaque -\nforming units; GMT, geometric mean titer; NAb, neutralizing antibody; RSV Annual revaccination: Participants receiving the first dose (Dose 1) of Arexvy  at Day 1, followed by a \nrevaccination dose at 12 months post Dose 1 and at 24 months post Dose 1; RSV M24 revaccination: Participants receiving the f irst dose (Dose 1) of Arexvy  at Day 1 followed by a \nrevaccination dose at 24 months post Dose 1.AReSVi -004 \nCO-9\nLower Prevaccination  RSV-B NAb Titers  Associated with Higher  \nSeroresponse  Rates (≥ 4 -Fold Increase) Following Revaccination\nPresentation by GSK at ACIP June 26, 2024*Participants were grouped into quartiles depending on their baseline NAb titers: 1 = baseline NAb min–<1; 2 = baseline NAb 1–<2 (median); 3 = baseline NAb 2 (median) –<3; \n4 = baseline NAb 3–4. Participants in the quartile 1 had the lowest pre -revaccination NAb and those in the quartile 4 had the highest; ED60, serum dilution inducing 60% inhibition in plaque -\nforming units; GMT, geometric mean titer; NAb, neutralizing antibody; RSV Annual revaccination: Participants receiving the first dose (Dose 1) of Arexvy  at Day 1, followed by a \nrevaccination dose at 12 months post Dose 1 and at 24 months post Dose 1; RSV M24 revaccination: Participants receiving the f irst dose (Dose 1) of Arexvy  at Day 1 followed by a \nrevaccination dose at 24 months post Dose 1.0%20%40%60%80%100%\n0 1 2 3 41 2 3 40%20%40%60%80%100%\n0 1 2 3 41 2 3 4\nQuartile* Quartile*58.2 \n(44.1, 71.3)\n37.5\n(24.9, 51.5)\n19.6 \n(10.2, 32.4)12.5 \n(5.2, 24.1)17.9 \n(9.6, 29.2)\n7.5 \n(2.5, 16.6)4.5 \n(0.9, 12.5)3.0 \n(0.4, 10.4)RSV Annual Revaccination RSV M24 Revaccination\nParticipants with \n≥ 4-fold increase \nin RSV-B NAb \ntiters at \nM13 vs M12\n[95% CI]Participants with \n≥ 4-fold increase \nin RSV-B NAb \ntiters at \nM25 vs M24\n[95% CI]\nn/N 12 / 67 5 / 67 3 / 67 2 / 67\nNAb baseline \nGMT (ED60)351 – <1,607 1,607 – <2,453 2,453 – <4,133 4,133 – 36,39132 / 55 21 / 56 11 / 56 7 / 56\n271 – <1,190 1,190 – <2,122 2,122 – <3,845 3,845 – 26,385AReSVi -004 \nCO-10\nSafety and Reactogenicity Profile in Individuals Revaccinated at \nMonth 24 Similar to First Dose\nSolicited AEs reported within 4 days of each vaccine dose (exposed set)\nAE, adverse event; M, month; RSV 24M revaccination: Participants receiving the first dose (Day 1 Dose) of RSVPreF3 OA investi gational vaccine at Day 1 followed by a revaccination \ndose at 24 months (M24 Dose) post -Dose 1 (n=270 -328). Grade 3: >100 mm for erythema and swelling; significant pain at rest, prev ents normal everyday activities for pain; prevents \nnormal activity for headache, fatigue, myalgia, and arthralgia; >39.0 °C (102.2 °F) for fever.RSV M24 Revaccination\n(Day 1 Dose)RSV M24 Revaccination \n(M24 Dose)\n020406080100\n% of \nParticipants\nM24 Revac\n(Day 1)\nM24 Revac\n(M24)\nM24 Revac\n(Day 1)\nM24 Revac\n(M24)\nM24 Revac\n(Day 1)\nM24 Revac\n(M24)\nM24 Revac\n(Day 1)\nM24 Revac\n(M24)\nM24 Revac\n(Day 1)\nM24 Revac\n(M24)\nM24 Revac\n(Day 1)\nM24 Revac\n(M24)\nM24 Revac\n(Day 1)\nM24 Revac\n(M24)\nM24 Revac\n(Day 1)\nM24 Revac\n(M24)Grade 3\n11.6 11.461.3\n56.1\n10.17.714.917.830.535.2\n1.5 1.921.326.332.6 31.1Arthralgia Fatigue Fever Headache Myalgia Erythema Pain Swelling\nUnsolicited AEs, SAEs, Fatal SAEs and pIMDs  of individuals who were revaccinated at Month 24 are also similar to those vaccinated at Day 1Local SystemicAReSVi -004 \nCO-11\nAReSVi -004 Summary\nRevaccination at a 24 -month interval provides higher RSV -A and RSV -B neutralizing antibody \ntiters as compared to a 12 -month interval 1\nSafety and reactogenicity profiles of second dose comparable with first dose 3\nThe l ower  the prevaccination  RSV-A and RSV -B neutralizing antibody titers  observed at 2 years \npost initial vaccination, the higher the seroresponse  rates after  revaccination 2\nPresentation by GSK at ACIP June 26, 2024\nFuture results from this trial will help inform optimal revaccination timing 4\nCO-12\nPostmarketing  Safety Update\nPresentation by GSK at ACIP June 26, 2024\nCO-13\nAREXVY: Post -Licensure Safety Surveillance  After 1 Year \nReflects Acceptable Safety Profile in Clinical Trials  \nPresentation by GSK at ACIP June 26, 2024*IQVIA NPA Rapid Weekly TRx, to 13 May 2024\n**Based on GSK safety database, spontaneous AE reports not necessarily causally -related to vaccination\n1. Sejvar  JJ, et al. 2011; AE: adverse event ; VSD: vaccine safety datalink; BEST: biologics effectiveness and safety \n▪1,640 AE reports received (launch 3 May ’23 -2 May ‘24)**\n▪82% from US\n▪89% non -serious\n▪Since launch, GSK received 12 reports of GBS, all from US\n▪Observed vs expected, based on 7,246,910 AREXVY doses administered \nin US and background incidence rate = 2.1 / 100,000 PY3\nVaccine \nExposure▪~ 8 million  doses  of AREXVY administered in US since launch*\nAE▪1,640 AEs (from US, 1,344 AE reports received) [launch 3 May ’23 -2 June ’24]**\n▪89% non -serious\n▪Majority related to labelled reactions\nGBS▪Since launch, GSK received 13 reports of GBS, all from US\n▪Reports do not exceed expected background incidence1 \n▪17 cases expected in absence of vaccination \n▪VSD and BEST initiative will provide additional assessment of GBS\nCO-14\nOverview of Clinical Development Program\nPresentation by GSK at ACIP June 26, 2024\nCO-15\nAREXVY Clinical Development Program\nAReSVi -004 study\nOlder adults ≥60 YOA\nSafety, reactogenicity, immunogenicity, persistence, and re -vaccination\nRSV OA=ADJ -019 study\nOlder adults ≥60 YOA\nSafety, reactogenicity, immunogenicity when \nco-administered with PCV20\nRSV OA=ADJ -020 study\nOlder adults ≥50 YOA\nSafety, reactogenicity, immunogenicity when \nco-administered with HZ/ su vaccine\nPhase 2b\nPhase 3\nCompleted\nOngoing/\nin progress\nRSV OA=ADJ -025 study\nAdults 18 –49 years of age compared \nto older adults ≥60 years of age\nSafety and immunogenicity\nRSV OA=ADJ -007,\nRSV OA=ADJ -017, RSV OA=ADJ -008\nSafety, reactogenicity, immunogenicity when \nco-administered with FLU -QIV, FLU -aQIV , \nFLU-QIV-HD, respectively\nRSV OA=ADJ -013 study\nOlder adults ≥50 YOA\nSafety, reactogenicity, immunogenicity when \nco-administered with COVID -19 mRNA \nvaccine\nPresentation by GSK at ACIP June 26, 2024FLU-aQIV : adjuvanted quadrivalent influenza vaccine; FLU -QIV: quadrivalent influenza vaccine; FLU -QIV-HD: high -dose quadrivalent influen za vaccine; HZ/ su: herpes zoster recombinant \nsubunit; 1MPD1: 1 month post dose 1; PCV20: 20 -valent pneumococcal conjugate vaccine; YOA: years of age\nAll studies ClinicalTrials.gov; All URLs accessed June 2024AReSVi -006 study\nOlder adults ≥60 YOA\nPivotal efficacy study\nRSV OA=ADJ -018 study\nAdults 50−59 YOA (incl. adults at\nincreased risk of RSV -LRTD) vs ≥60 YOA\nSafety, reactogenicity, immunogenicity\nRSV OA=ADJ -023 study\nImmunocompromised adults ≥18 YOA \n(lung and renal transplant recipients)\nSafety and immunogenicity\n\nCO-16\nAREXVY (Single dose)AREXVY Placebo% VE (95% CI)\nW/ season \ncovariateW/o season \ncovariateNumber of events (n/N) \nRSV-LRTD 32 / 12,468 154 / 12,498 67.7%  (52.3, 78.7) 73.3%  (60.7, 82.4)\n≥ 1 comorbidity of interest* 17 / 5,000 79 / 4,942 67.1%  (43.6, 81.8) 73.1% (54.2, 85.1)\n≥ 70 years of age 12 / 5,506 74 / 5,517 74.6% (52.6, 87.5) 79.1% (61.3, 89.7)\nPre-frail** 9 / 4,794 50 / 4,779 71.3% (40.6, 87.7) 77.0% (52.7, 90.1)\nSevere RSV-LRTD 9 / 12,468 54 / 12,498 74.9%  (48.4, 89.2) 78.6% (56.3, 90.7)\nVaccine Efficacy0% 20% 40% 60% 80% 100%Efficacy of a Single Dose of AREXVY over 2 Calendar Years \nPresentation by GSK at ACIP June 26, 2024\nMedian follow-up: 23.3 monthsAReSVi -006 \n*Comorbidities of interest: COPD, asthma, any chronic respiratory or pulmonary disease, heart failure (cardiorespiratory cond ition), diabetes mellitus type 1 or 2, advanced liver or renal\ndisease (endocrine or metabolic condition); **frailty assessed using gait speed test: walking speed < 0.4 m/s or not able to perform test (frail), walking speed 0.4 –0.99 m/s\n(pre-frail), walking speed ≥1 m/s (fit); Due to too few cases observed, cannot conclude VE  for frail and ≥ 80 years of age\nCO-17\nConclusion\n▪Immunogenicity data supports potential for revaccination with AREXVY\n▪Stronger immune responses were observed in those revaccinated after \n24-month interval compared to those revaccinated annually \n▪Results from ongoing Phase 3 studies will help inform timing of \nrevaccination\n▪AREXVY provides protection over 2 calendar years\n▪Acceptable safety profile following administration of ~ 8 million doses\n▪FDA recently expanded AREXVY’s indication to include use in individuals \n50–59 YOA at increased risk for RSV-LRTD\n▪Will help to close equity gap by broadening access for populations at \nincreased risk for severe disease caused by RSV\nCO-18\nAREXVY (Adjuvanted RSVPreF3) \n2-Year Update\nACIP June 26, 2024\nSusan Gerber, MD\nMedical Director \nPresentation by GSK at ACIP June 26, 2024", "summary": "CO-1 AREXVY (Adjuvanted RSVPreF3)  2-Year Update ACIP June 26, 2024 Susan Gerber, MD Medical Director  GSK Presentation by GSK at ACIP June 26, 2024 CO-2 AREXVY Indications  AREXVY now indicated for active immunization for prevention of lower  respiratory tract disease (LRTD) caused by RSV in ▪Individuals ≥ 60 YOA ▪Individuals 50-59 YOA at increased risk for LRTD caused by RSV YOA: years of age FDA, 2024. AREXVY Prescribing Information (PI); https://www.fda.gov/media/167805/download (URL…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/03-RSV-Adult-Gerber-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 18}
{"title": "04 RSV Adult Das 508", "content": "1\nUpdate on Moderna’s RSV Vaccine, \nmRESVIA (mRNA -1345), in Adults \n≥60 Years of Age\nAdvisory Committee on Immunization Practices (ACIP)\nRituparna Das, MD PhD\nJune 26, 2024\n2\nLicensure of mRESVIA, Moderna’s RSV Vaccine \n(mRNA -1345) in United States \n▪FDA approval obtained May 31, 2024\n▪Indication/Presentation\n▪For active immunization for the prevention of lower respiratory \ntract disease (LRTD) caused by respiratory syncytial virus (RSV) \nin adults 60 years of age and older\n▪Single dose regimen\n▪Prefilled syringe\n3\nOutline of \nPresentation▪Pivotal Phase 2/3 Trial\n▪Brief review of study design\n▪Update on safety\n▪Update on efficacy\n▪12-month revaccination data\n▪Safety\n▪Immunogenicity\n▪Summary\n4\nPivotal Safety and Efficacy Study Design\nPopulation\n▪Healthy adults including those with chronic, stable medical conditions, and/or frailty \n▪≥ 60 years of age\n▪22 countries (both Northern and Southern Hemisphere)\nRegimen and follow -up\n▪Single -dose regimen (1:1 50 μg RSV vaccine or saline placebo)\n▪24-month follow -up\nStratified by \n▪Age (60 - 74 and ≥ 75 years)\n▪Presence or absence of congestive  heart failure or chronic  obstructive pulmonary \ndiseaseStudy 301\nclinicaltrials.gov NCT05127434 https://clinicaltrials.gov/ct2/show/NCT05127434\nWilson et al NEJM , 2023.\n5\n▪RSV efficacy study \nconducted across 3 \nseasons\n▪>50% of participants \nenrolled in US\n▪Primary Analysis: \nMet success criteria\n▪Additional Analysis: \n>90% of participants \nfollowed for ≥ 6 months\n▪March 2024 Analysis: \n>90% of participants \nfollowed for ≥12 monthsTrial Analyses\nUS 2021 -2023 RSV Hospitalization Rates (RSV -NET) in Adults ≥ 65 Years1\nOverall RSV \nHospitalization \nRate per \n100,000 Adults \n≥ 65 Years1 \n012345678910\n2021 -2022 \nRSV SeasonAdditional Analysis\nNovember 2021 – April 2023\nMedian 8.6 Months (range 0.5 – 17.7) \nFollow -upVaccination Period\nNovember 2021 – December 2022\nPrimary Analysis \nNovember 2021 – November 2022\nMedian 3.7 Months (range 0.5 - 12.6) \nFollow -up\n2022 -2023 \nRSV SeasonMarch 2024 Analysis\nNovember 2021 – March 2024\nMedian 18.8 Months (range 0.5 – 24) \nFollow -up\n1. CDC. Respiratory Syncytial Virus Hospitalization Surveillance Network (RSV -NET). https://www.cdc.gov/respiratory -viruses/data -research/dashboard/most -impacted -hospitalizations.html 2023 -2024 \nRSV Season\n2021 2022 2023 2024\n6\nTiming of Vaccination and RSV Surveillance\nVaccination\n▪COVID -19 pandemic precluded the assumption of standard RSV seasons\n▪Subjects vaccinated year -round for ~ 1 year (not limited to pre -RSV season)\nSurveillance\n▪Active surveillance of >36,000 participants for RSV year -round (not limited to RSV seasons) \n▪Included 2022/2023 and 2023/2024 high incidence RSV seasons1\n▪Background rates in placebo recipients, 14 days - 24 months:\n▪RSV-LRTD with ≥ 2 symptoms: 9.3 cases/1000 person years\n▪RSV-LRTD with ≥ 3 symptoms: 3.7 cases/1000 person years\n▪RSV-ARD: 16.4 cases/1000 person years\n▪683 confirmed RSV -ARD cases reported over 24 months  Study 301\nclinicaltrials.gov NCT05127434 https://clinicaltrials.gov/ct2/show/NCT05127434\n1. CDC. Respiratory Syncytial Virus Hospitalization Surveillance Network (RSV -NET). https://www.cdc.gov/respiratory -viruses/data -research/dashboard/most -impacted -hospitalizations.html\n7\nDemographics of Study Participants\nCharacteristicRSV Vaccine (mRNA -1345)\n(N = 18,427)Placebo\n(N = 18,387)\nMedian Age, years 67 67\nMale, n (%) 9,410 ( 51%) 9,330 (51%)\nAge Group, n (%)\n60 – 69 Years 11,437 (62%) 11,399 (62%)\n70 – 79 Years 5,546 (30%) 5,534 (30%)\n≥ 80 Years 1,444 (8%) 1,454 (8%)\nRace/Ethnicity, n (%)\nWhite 11,311 (61%) 11,290 (61%)\nBlack or African American 2,204 (12%) 2,173 (12%)\nAsian 2,151 (12%) 2,138 (12%)\nHispanic / Latino Ethnicity 6,117 (33%) 6,168 (34%)\nFrailty Status ( ≥4 on Edmonton frail score)  3,862  (21%) 3,946 (21%)Study 301\nAge, gender, race/ethnicity, and frailty status balanced between vaccine and placebo recipients\nRace/ethnicity generally representative of US populationRandomization Set\nMarch 8, 2024 data cutoff\n8\nPrespecified Comorbidities among Study Population\nRSV Vaccine (mRNA -1345)\n(N = 18,427)Placebo\n(N = 18,387)\n ≥1 Prespecified Comorbidity  (%) 5,463 (30%) 5,357 (29%)\nChronic obstructive pulmonary disease (COPD) 1,097 (6%) 1,112 (6%)\nAsthma 1,410 (8%) 1,365 (7%)\nChronic Respiratory Disease189 (0.5%) 84 (0.5%)\nDiabetes 3,292 (18%) 3,207 (17%)\nCongestive Heart Failure (CHF) 276 (2%) 268 (2%)\nAdvanced Liver Disease 49 (0.3%) 44 (0.2%)\nAdvanced Renal Disease 111 (0.6%) 127 (0.7%)Study 301 – Randomization Set\n•~30% of study participants with comorbidities\n•Comorbidities balanced between vaccine and placebo recipients\n1. Chronic respiratory disease includes chronic pulmonary fibrosis (idiopathic and otherwise), restrictive lung disease, asbe stosis, bronchiectasis, cystic fibrosis, \npulmonary hypertension, sarcoidosis, and history of tuberculosis\nMarch 8, 2024 data cutoffRandomization Set\n9\nSafety Data\nStudy 301\nSafety Set – March 8, 2024 data cutoff\nBased on median of 18.8 months of follow -up\n10Unsolicited Adverse Events Within 28 Days After Injection, \nRegardless of Relationship  to Vaccine/Placebo\nRSV Vaccine (mRNA -1345)\n(N = 18,369)Placebo\n(N = 18,316)\n All, n (%) 3,823 (21%) 3,467 (19%)\nSerious 126 (0.7%) 114(0.6%)\nFatal 2(<0.1%) 6 (<0.1%)\nMedically -Attended 1,664 (9%) 1,587 (9%)\nLeading to Study Discontinuation 2(<0.1%) 11(<0.1%)\nSevere/ ≥ Grade 3 138(0.8%) 138(0.8%)\nNon-Serious 3,697 (20%) 3,353 (18%)\nAny Adverse Event of Special Interest  (AESI) 3(<0.1%) 9(<0.1%)Study 301\nNo imbalances in any categories between vaccine and placebo recipientsSafety Set\nMarch 8, 2024 data cutoff\n11\nAdverse Events of Special Interest (AESI)\n▪Neurological Disorders\n▪No cases of acute disseminated encephalomyelitis (ADEM)\n▪No safety concern with Guillain -Barre syndrome (3 unrelated cases reported >500 days \npostinjection [1 vaccine, 2 placebo])  \n▪No imbalance observed for other neurological disorders including Bell’s palsy/facial \nparalysis\n▪Cardiac Events\n▪No imbalance observed in cardiac arrhythmias such as atrial fibrillation\n▪No confirmed cases of:\n▪Acute myocarditis in vaccine recipients\n▪Acute pericarditis in vaccine recipients with onset < 42 daysStudy 301 \nSafety Set\nMarch 8, 2024 data cutoff\n12\nEfficacy Analyses\nStudy 301\n13\nEfficacy of mRNA -1345 Against RSV LRTD among Adults ≥ 60 Years\nCases, n (%)Primary Analysis (Case Driven)1\n3.7 Months Median (range 0.5 - 12.6) Follow -up Additional Analysis1\n8.6 Months Median (range 0.4 – 17.7) Follow -up\nRSV Vaccine \n(mRNA -1345)\n(N = 17,561)Placebo\n(N = 17,503)Vaccine \nEfficacy \n(%CI*)RSV Vaccine \n(mRNA -1345)\n(N = 18,074)Placebo\n(N = 18,010)Vaccine \nEfficacy \n(% CI*)\nRSV LRTD\n≥ 2 symptoms15 (0.09%) 70 (0.40%)78.7%  \n(62.8%, 87.9%)48 (0.27%) 127 (0.71%)62.5%  \n(47.7%, 73.1%)\nRSV LRTD\n≥ 3 symptoms5 (0.03%) 26 (0.15%)80.9% \n(50.1%, 92.7%)20 (0.11%) 51 (0.28%)61.1% \n(34.7%, 76.8%)Study 301 – Primary and Additional Analyses\n▪Vaccine protection continued through a high incidence RSV season (2022/2023)\n▪Lower bound of confidence interval continued to exceed 20%Per Protocol Analysis\n1.US product insert mRESVIA\n* For primary analysis, the alpha -adjusted 95.04% CI and 95.10% CI for RSV LRTD ≥ 2 symptoms and ≥ 3 symptoms are presented, res pectively. \n  For additional analysis, 95% CIs are presented.\n  Efficacy based on hazard ratios\n14Efficacy of mRNA -1345 Against RSV LRTD among Adults ≥ 60 Years - \n18 Month Analysis \nStudy 301 - Per Protocol Set\n▪Vaccine protection continued over a longer period through high incidence 2022/2023 and 2023/2024 RSV \nseasons\n▪Lower bound of the confidence interval continued to exceed 20%Cases, n (%)\nRSV Vaccine \n(mRNA -1345)\n(N = 18,181)Placebo\n(N = 18,132)Vaccine Efficacy (%) \n(95% CI)\nRSV LRTD\n≥ 2 symptoms113 (0.6%) 225 (1.2%)50.3%  \n(37.5%, 60.7%)\nRSV LRTD\n≥ 3 symptoms46 (0.3%) 91 (0.5%)49.9%\n(27.8%, 65.6% )March 2024  Analysis\nMarch 8, 2024 data cutoff\n Efficacy based on incidence rates adjusted for person -time. \n15Efficacy of mRNA -1345 by Age, Comorbidities, and Frailty \nAgainst RSV LRTD ≥ 2 Symptoms  \nStudy 301 - Per-Protocol Efficacy Set through 24 Months\n▪Case splits favorable for mRNA -1345 with respect to age, comorbidities, and frailty through 24 monthsNumbers of Events\nRSV LRTD with ≥ 2 Symptoms RSV Vaccine \n(mRNA -1345)\n(N = 18,181)Placebo\n(N = 18,132)Vaccine Efficacy\n(95% CI)\nOverall 132/18,181 248/18,132 47.4% (35.0, 57.4)\nAge60 – 69 Years 83/11,269 147/11,238 44.3%  (27.1, 57.4)\n70 – 79 Years 36/5,487 81/5,459 56.0%  (34.9, 70.3)\n≥ 80 Years 13/1,425 20/1,435 35.3% (-30.1, 67.8)\nComorbiditiesNo Comorbidities 99/12,788 160/12,856 38.6%  (21.1, 52.2)\n≥ 1 Comorbidities 33/5393 88/5276 63.4%  (45.4, 75.5)\nFrailty StatusFit (0-3) 106/13,491 197/13,366 47.2%  (33.1, 58.3)\nVulnerable/Frail (≥ 4) 20/3802 39/3872 48.0%  (10.9, 69.7)\n-40 -20 0 20 40 60 80 100\nVaccine Efficacy, % (95% CIs)\nComorbidities include COPD, CHF, asthma, chronic respiratory disease, diabetes, advanced liver disease, advanced renal diseas e\nMarch 8, 2024 data cutoff\n16\nEfficacy of mRNA -1345 Against Severe LRTD Among Adults ≥ 60 Years\nStudy 301 - Post Hoc Analysis/Per Protocol Set\n1.Falsey et al NEJM, 2005; 2. Panozzo et al ESWI, 2023▪Shortness of breath is a key driver of seeking a higher level of care1,2 \n▪Vaccine is efficacious in preventing shortness of breath associated with RSV -LRTD\n▪Too few hospitalizations to assess vaccine efficacyVaccine Efficacy (95% CI)\nPrimary Analysis  \n3.7 Months Median \n(0.5 - 12.6) Follow -up Additional Analysis \n8.6 Months Median \n(0.4 – 17.7) Follow -upMarch 2024 Analysis, \n18 Month \nRSV-LRTD Associated \nShortness of Breath1,286.7% \n(41.9%, 97.0%)74.6%\n(50.7%, 86.9%)56.7%\n(33.1%, 72.6%)\n17Efficacy of mRNA -1345 Against RSV LRTD with ≥ 2 Symptoms \nAmong Adults ≥ 60 Years Over Time\nStudy 301 – Post Hoc Analysis \n~2.4%/month\ndecrease \nMonths Following VaccinationVaccine\nEfficacy\n(%)\n20406080100\n2 4 6 8 10 12 14 16 18\nWeighted least square regression line and 95% CI (blue area) based on the bi -monthly VEs calculated using incidence rates adjust ing person time \nover two -month periods\n18\nPersistence of RSV Antibody and Revaccination \nat 12 Months \nStudy 302\n19\nVaccination Regimen\nStudy 302, Parts B & C\nNDay 1 12 Months\nRSV Vaccine \n(mRNA -1345) Placebo 254\nRSV Vaccine \n(mRNA -1345)\nRSV Vaccine\n(mRNA -1345)COVID -19 \nBivalent Vaccine289Study 302, Part B Study 302, Part C\nParticipants from Study 302, Part B, were enrolled in Part C and revaccinated with RSV vaccine at 12 months\n20Safety Events of Interest – Revaccination at 12 Months \nwith mRNA -1345 \n▪No reports of: \n▪Deaths, SAEs, or AESIs as assessed as related by the \ninvestigator\n▪Anaphylaxis\n▪Guillain Barre Syndrome\n▪Acute disseminated encephalomyelitis (ADEM)\n▪Bell’s palsy/facial paralysis\n▪Acute myocarditis or acute pericarditisStudy 302 C  – Based on 2 Months Follow -up\nSafety Set\nSAE –serious adverse event; AESI –adverse event of special interest \nDec 4, 2023 data cutoff\n21Durability of Neutralizing Antibody Responses Following Primary Dose and \nRevaccination at 12 Months with mRNA -1345\nStudy 302C – Adults ≥50 Years  \n214818283\n455419662\n100100010000100000\n0 1 2 3 4 5 6 7 8 9 10 11 12 13 14RSV-A Neutralizing Antibody\nGMT\nPart C\n12 Month RevaccinationPart B\nDose 1\nGMR of \nrevaccination vs \nfirst dose:\n▪ RSV-A - 1.08 \n(0.99, 1.17)\n▪RSV-B - 0.91 \n(0.84, 0.99)\nNon-inferiority \ncriteria met (LB of \n95% CI of GMR > \n0.667) for RSV -A \nand RSV -BGMFR from Day 0 8.5 9.2\n▪RSV-A and RSV -B neutralizing antibodies detectable at 12 months post -vaccination\n▪Revaccination with mRNA -1345 as soon as 1 year after primary vaccination elicits responses similar to that following \nprimary vaccination\n▪Revaccination met pre -specified non -inferiority success criteriaStudy Month2.1\n22\nSUMMARY\n23\nRSV Vaccine (mRNA -1345)\n▪Vaccine generally well tolerated in >19,700 adults ≥ 60 years  vaccinated with 50 g \nlicensed dose \n▪No ADEM, no vaccine -related cases of GBS, or other safety concerns\nSafety\n▪Efficacious through median of ~19 months follow -up\n▪Comparable efficacy in individuals ≥ 80-year-olds, with ≥ 1 comorbidity, and frail\n▪Shown to prevent severe RSV disease based on analysis of shortness of breath\n \nEfficacy  \n▪Strong humoral and cellular immune responses1 (ACIP Feb 2024)\n▪Neutralizing antibody detectable through 12 months post -vaccination\n▪Revaccination with mRNA -1345 as soon as 1 year after primary vaccination elicits \nresponses similar to that following primary vaccination\n▪Revaccination well tolerated; no safety concerns\nImmunogenicity/\nRevaccination\n▪Pre-specified immunogenicity criteria met & and no new safety concerns observed with \nconcomitant administration of mRNA -1345 with standard influenza & COVID -19 vaccines \n(ACIP Feb 2024)\nConcomitant \nAdministrationSummary\n1 Goswami et al, JID, 2024\n24\nTHANK YOU! \n24▪Investigators\n▪Study site personnel\n▪Laboratory personnel\n▪Most importantly, the individuals who \nparticipated in these trials", "summary": "1 Update on Moderna’s RSV Vaccine,  mRESVIA (mRNA -1345), in Adults  ≥60 Years of Age Advisory Committee on Immunization Practices (ACIP) Rituparna Das, MD PhD June 26, 2024 2 Licensure of mRESVIA, Moderna’s RSV Vaccine  (mRNA -1345) in United States  ▪FDA approval obtained May 31, 2024 ▪Indication/Presentation ▪For active immunization for the prevention of lower respiratory  tract disease (LRTD) caused by respiratory syncytial virus (RSV)  in adults 60 years of age and older ▪Single dose…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/04-RSV-Adult-Das-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 24}
{"title": "05 RSV Adult Donahue 508", "content": "Update: Rapid Cycle Analysis of RSV \nVaccines in Older Adults\nJim Donahue, PhD DVM\nMarshfield Clinic Research Institute\nPresented to the ACIP\nJune 26, 2024\n1\nRSV RCA Interim Report – June 26, 2024\n•Description of Vaccine Safety Datalink and RCA\n•Review of surveillance methods\n•Descriptive analysis\n•Sequential analysis\n̶Immune thrombocytopenia (ITP)\n̶Guillain -Barré syndrome (GBS)\n̶Atrial fibrillation\n2\nVaccine Safety Datalink 2024\n*\n3•Collaborative project between CDC and 13 integrated healthcare organizations\n•Data on ~13.5 million persons per year \n•Conducts rigorous vaccine safety studies and near -real-time monitoring\nVSD Rapid Cycle Analyses (RCA)\n4•Permits rapid assessment of vaccine safety \n-Near real -time data for weekly, biweekly, or monthly analyses\n•Outcome incidence in vaccinated persons compared to outcomes \nincidence in a comparator group\n-Outcomes are pre -specified\n•Sequential analytic methods used to detect ‘statistical signals’ \nwhile maintaining a pre -defined type I error rate\n-Type I error = mistakenly reject the null hypothesis (“false positive”)\n•Statistical signals are interpreted as potential  associations\nObjectives for RSV RCA in Older Adults\n5•Monitor RSV vaccine uptake\n•Monitor the occurrence of pre -specified outcomes following RSV \nvaccination\n•Conduct near real -time surveillance of pre -specified outcomes \nusing RCA methods\nStudy Design and Population\n6•Near real -time surveillance among a prospective cohort of \npersons ≥60 years old who received an RSV vaccine\n•Member of a participating VSD infrastructure site\n•Data are extracted every week and analyses are biweekly\n•Surveillance period: 8/1/2023 through 5/31/2025\n-Sequential analyses started in March 2024\n•Project ends September 2025\nSequential Analysis Methods\n7•Biweekly analysis includes a sequential test of the one -sided null \nhypothesis that the vaccine does not increase the risk in the risk interval\n•A ‘statistical signal’ occurs when the analysis produces a one -sided P value \nthat is less than a pre -specified threshold\n•The signal threshold is determined from an alpha -spending plan that keeps \nthe overall chance of a Type 1 error <0.05 during the surveillance period \n•Formal sequential analysis stops after a signal, but surveillance continues\n•Design and analysis is analogous to that used in the VSD RCA of COVID -19 \nvaccines (Klein N, et al. JAMA 2021; 326:1390 –9)\nRisk and Comparison Intervals\n8•Primary risk interval for all outcomes will be 1 -21 days following \nRSV vaccination except anaphylaxis and CIDP*\n-Primary comparison interval of 43 -63 days\n-Secondary comparison interval of 22 -42 days\n•Secondary risk interval of 1 -42 days\n-Comparison interval of 43 -84 days\n•Anaphylaxis and CIDP will be descriptively monitored only\n-Anaphylaxis (0 -1 days after RSV vaccination)\n-CIDP (1 -84 days after RSV vaccination)\n*chronic inflammatory demyelinating polyneuropathy\nAnalysis with Vaccinated Concurrent Comparators\n9•Comparators are RSV vaccinees, who on the same day  as the exposed case \nin a risk interval, were in the same stratum (e.g., age, sex, race/ethnicity, \nVSD site), but in a comparison interval\n•Outcome incidence is calculated during the risk interval and compared \nwith incidence in the comparison interval\n-Relative risk estimates are computed with nominal 95% confidence intervals \n-Adjusted for calendar day, age group, sex, race/ethnicity, VSD site\n•Advantages of vaccinated concurrent comparators compared to \nunvaccinated or historical comparators\n-Permits adjustment for potential biases due to calendar time, site, and demographic \nfactors\n-Less confounding by indication (e.g., persons with chronic illness more likely to seek \nRSV vaccination and may be at increased risk of atrial fibrillation)\n10RSV vaccinated \nMay 30th \nRSV vaccinated \nApril 19th June 3rdJune 3rd1 21\n43 63On each calendar day that an outcome occurs in a \nvaccinee (e.g., June 3rd ), we compare vaccinees in \ntheir risk interval (1 -21 days) with similar vaccinees \nin their comparison interval (43 -63 days). \n‘Similar’ means that people were in the same age \ngroup, sex, race/ethnicity, and VSD site. \nInherently adjusts for calendar time.Risk interval 1 -21 days post -vaccination\nComparison interval 43 -63 days post -vaccination\nRef: Klein N, et al. Kaiser Permanente Northern CaliforniaVaccinated Concurrent Comparator Design\nFour Exposure Groups\n11GSK with simultaneous vaccination of another vaccine*\nGSK without simultaneous vaccination\nPfizer with simultaneous vaccination of another vaccine*\nPfizer without simultaneous vaccination\n*Non -RSV vaccines typically include routine, age -appropriate vaccines such as \nCOVID -19, influenza, RZV, PCV20/15, PPSV23,  Td/Tdap \nPre-specified Outcomes (n=14)\n12Outcome Setting1Primary risk \ninterval (days)2\nAcute disseminated encephalomyelitis (ADEM)3E, I 1-21\nAcute myocardial infarction (AMI) E, I 1-21\nAnaphylaxis3 E, I 0-1\nAtrial fibrillation E, I, O, T 1-21\nBell’s palsy E, I, O, T 1-21\nChronic inflammatory demyelinating polyneuropathy (CIDP)3 E, I, O, T 1-84\nDeep vein thrombosis (DVT) E, I, O, T 1-21\nEncephalitis / myelitis / encephalomyelitis (not ADEM or TM) E, I 1-21\nGuillain -Barré syndrome (GBS)3 E, I 1-21\nImmune thrombocytopenia (ITP) E, I, O, T 1-21\nMyocarditis / pericarditis E, I 1-21\nPulmonary embolism (PE) E, I 1-21\nStroke E, I 1-21\nTransverse myelitis (TM)3 E, I 1-21\n1E=Emergency department; I=Inpatient; O=Outpatient; T=Telehealth\n2All outcomes also have a secondary risk interval of 1 -42 days after vaccination, except anaphylaxis and CIDP , which are descript ively monitored only . \n3Chart review regardless of whether there is a statistical signal; sequential analyses will use only chart -confirmed cases (ADEM, GBS, and TM). \nRSV Vaccines Administered in VSD, \n8/1/2023 –5/25/2024\n13•NOTE: All subsequent analyses and slides exclude RSV vaccines in the \n‘Unspecified’ manufacturer categoryGSK Pfizer UnspecTotal\nN % N % N %\n338,290 87.7 47,287 12.3 152 0.0 385,729\n14050001000015000200002500030000\n07-30-23\n08-06-23\n08-13-23\n08-20-23\n08-27-23\n09-03-23\n09-10-23\n09-17-23\n09-24-23\n10-01-23\n10-08-23\n10-15-23\n10-22-23\n10-29-23\n11-05-23\n11-12-23\n11-19-23\n11-26-23\n12-03-23\n12-10-23\n12-17-23\n12-24-23\n12-31-23\n01-07-24\n01-14-24\n01-21-24\n01-28-24\n02-04-24\n02-11-24\n02-18-24\n02-25-24\n03-03-24\n03-10-24\n03-17-24\n03-24-24\n03-31-24\n04-07-24\n04-14-24\n04-21-24\n04-28-24\n05-05-24\n05-12-24\n05-19-24Vaccines RSV Vaccinations by Manufacturer and Week of \nAdministration\nGSK\nPfizer\nTotal\nWeekStart of \nsequential \nanalysis\nResults of Sequential Analysis\nSix runs —data through 5/25/2024\n15\nVSD Outcomes Setting1Signal\n(Y/N)\nAcute disseminated encephalomyelitis (ADEM) E, I N\nAcute myocardial infarction (AMI) E, I N\nAtrial fibrillation (AF) E, I, O, T N\nBell’s palsy (BP)   E, I, O, T N\nDeep vein thrombosis (DVT) E, I N\nEncephalitis / myelitis / encephalomyelitis (ENCEPH) E, I N\nGuillain -Barré syndrome (GBS) E, I N\nImmune thrombocytopenia (ITP) E, I, O, T Y\nMyocarditis / pericarditis ( MYOC ) E, I N\nStroke (STK) E, I N\nTransverse myelitis (TM) E, I N\nPulmonary embolism (PE) E, I N16RSV RCA Vaccine Statistical Signals in VSD (5/25/2024) \n1E = ED, I = Inpatient, O = Outpatient, T=Telehealth\nAnalysis Parameters Signal Information and Informative Counts Nominal AnalysisSequential \nTest\nOutcome \nEventRisk \nInterval \nDaysComp \nInterval \nDaysVaccine \nTypeSignaled \nin a \nPrior \nRun1New \nSequential \nAnalysis \nSignal2Events \nin Risk \nIntervalEvents in \nComp \nIntervalAdjusted \nExpected \nEvents in \nRisk \nIntervalAdjusted \nRate \nRatio395%\nConfidence \nInterval42-sided \nP Value1-sided\nP Value5\nITP 1-21 43-63 GSK w simul n/a No 2 1 0.6 3.08 0.23-92.44 0.408 0.347\nGSK wo simul n/a No 19 8 8.1 2.35 0.99-5.97 0.054 0.040\nPfizer w simul n/a No 0 1 0.2 0.00 0.00-81.18 0.810 0.810\nPfizer wo simul n/a No 2 2 1.8 1.10 0.11-11.27 0.931 0.659\n22-42 GSK w simul n/a No 3 2 1.4 2.21 0.31-19.61 0.432 0.340\nGSK wo simul n/a Yes 19 6 6.3 3.04 1.22-8.47 0.016 0.012\nPfizer w simul n/a No 0 1 1.1 0.00 0.00-16.74 0.468 0.468\nPfizer wo simul n/a No 2 1 0.7 2.67 0.20-78.89 0.472 0.394\n1-42 43-84 GSK w simul n/a No 4 7 4.3 0.93 0.22-3.42 0.931 0.662\nGSK wo simul n/a No 25 14 15.6 1.60 0.80-3.28 0.186 0.121\nPfizer w simul n/a No 1 3 3.5 0.29 0.01-4.25 0.428 0.957\nPfizer wo simul n/a No 3 3 3.4 0.88 0.14-5.47 0.888 0.718VSD RCA of RSV Vaccine in Older Adults\nSurveillance Initiated on 01AUG2023, Analyses Based on Data Through 16MAR2024 (run #1, week #1836)\nConcurrent Comparator Sequential Analysis Signal Assessment for Immune Thrombocytopenia\n---Age:60+ yrs---\n17\nAnalysis Parameters Signal Information and Informative Counts Nominal AnalysisSequential \nTest\nOutcome \nEventRisk \nInterval \nDaysComp \nInterval \nDaysVaccine \nTypeSignaled \nin a \nPrior \nRun1New \nSequential \nAnalysis \nSignal2Events \nin Risk \nIntervalEvents in \nComp \nIntervalAdjusted \nExpected \nEvents in \nRisk \nIntervalAdjusted \nRate \nRatio395%\nConfidence \nInterval42-sided \nP Value1-sided\nP Value5\nITP 1-21 43-63 GSK w simul n/a No 2 1 0.6 3.08 0.23-92.44 0.408 0.347\nGSK wo simul n/a No 19 8 8.1 2.35 0.99-5.97 0.054 0.040\nPfizer w simul n/a No 0 1 0.2 0.00 0.00-81.18 0.810 0.810\nPfizer wo simul n/a No 2 2 1.8 1.10 0.11-11.27 0.931 0.659\n22-42 GSK w simul n/a No 3 2 1.4 2.21 0.31-19.61 0.432 0.340\nGSK wo simul n/a Yes 19 6 6.3 3.04 1.22-8.47 0.016 0.012\nPfizer w simul n/a No 0 1 1.1 0.00 0.00-16.74 0.468 0.468\nPfizer wo simul n/a No 2 1 0.7 2.67 0.20-78.89 0.472 0.394\n1-42 43-84 GSK w simul n/a No 4 7 4.3 0.93 0.22-3.42 0.931 0.662\nGSK wo simul n/a No 25 14 15.6 1.60 0.80-3.28 0.186 0.121\nPfizer w simul n/a No 1 3 3.5 0.29 0.01-4.25 0.428 0.957\nPfizer wo simul n/a No 3 3 3.4 0.88 0.14-5.47 0.888 0.718VSD RCA of RSV Vaccine in Older Adults\nSurveillance Initiated on 01AUG2023, Analyses Based on Data Through 16MAR2024 (run #1, week #1836)\nConcurrent Comparator Sequential Analysis Signal Assessment for Immune Thrombocytopenia\n---Age:60+ yrs---\n18\n•ITP signal for GSK vaccine without simultaneous vaccination in \n1-21 day risk interval versus 22 -42 day comparison interval\n•Quick medical record reviews\n-Of the 19 cases in the risk interval, 4 were incident ITP*\n-Of the 14 cases in comparison intervals, 2 were incident ITP , 1 in the \n22-42 day interval and 1 in the 43 -63 day interval\n•After quick review: 4 cases of ITP in the primary risk interval, 1 \ncase each in the 22 -42 and 43 -63 day comparison intervals\n•Plan to do more detailed chart review of ITP cases going forwardITP Statistical Signal and Rapid Review\n19*New cases of ITP relative to RSV vaccination.\nGBS Cases Following RSV Vaccination\n--No Statistical Signal --\n20\nGBS Cases 1 -84 Days after RSV Vaccination\n•GBS cases identified electronically, then receive medical record review, \nand presumptive cases are adjudicated by two reviewers \n•Cases defined using Brighton Level (BL) criteria*\n•7 cases of GBS (BL 1 -3) following any RSV vaccination \n̶5 following GSK –  onset days 6, 10, 31, 54, 76 \n̶2 following Pfizer – onset days 9, 46\n•2 BL 4 cases following GSKAutomated  \nCasesCompleted \nChart ReviewChart Confirmed \nCasesNot \nGBSCases Pending \nReview\n12 11 9 2 1\n21*Sejvar  J, et al. Vaccine. 2011;29(3):599 -612.\n22Analysis Parameters Signal Information and Informative Counts Nominal AnalysesSequential \nTest\nOutcome \nEventRisk \nInterval \nDaysComp \nInterval \nDays Vaccine TypeSignaled \nin a Prior \nRun2New \nSequential \nAnalysis \nSignal3Events \nin Risk \nIntervalEvents in \nComparison \nIntervalAdjusted \nExpected \nEvents in Risk \nIntervalAdjusted \nRate \nRatio495% \nConfidence \nInterval52-sided \nP value1-sided \nP value6\nGBS11-21 43-63 GSK wo simul No No 2 1 0.9 2.33 0.10-93.95 0.603 0.515\nPfizer wo simul No No 1 0 0.0 ne 0.05-ne 0.496 0.496\n22-42 GSK wo simul No No 2 1 1.3 1.55 0.11-47.77 0.775 0.600\nPfizer wo simul No No 1 0 0.0 ne 0.07-ne 0.439 0.439\n1-42 43-84 GSK wo simul No No 3 1 1.4 2.17 0.16-74.98 0.605 0.501\nPfizer wo simul No No 1 0 0.0 ne 0.04-ne 0.557 0.557---Age:60+ yrs---VSD RCA of RSV Vaccine in Older Adults  \nSurveillance Initiated on 01AUG2023, Analyses Based on Data Through 25MAY2024 (run #6, week #1846) \nConcurrent Comparator Sequential Analysis Signal Assessment for Guillain -Barre Syndrome\n(1) Chart -confirmed cases only, Brighton level 1 -3\n(2) n/a = not applicable\n(3) No prior signal, at least 2 events in the risk interval, 1 -sided P value < 0.014\n(4) Adjusted for calendar date, VSD site, age category, sex, and race/ethnicity\n(5) ne = not estimable\n(6) Red: new sequential analysis signal, Yellow: 1 -sided P value < 0.014 but already signaled in a prior run\nCrude GBS Incidence Rates after RSV Vaccination1\n23Vaccine Risk interval# of \nCases# of \nDoses2Rate Per Million \n(95% CI)Rate per 100,000 PY \n(95% CI)\nGSK 1-21 days 2 323929 6.2 (0.7 – 22.3) 10.7 (1.3 – 38.8)\nGSK 1-42 days 3 323929 9.3 (1.9 – 27.1) 8.1 (1.7 – 23.5)\nPfizer 1-21 days 1 45162 22.1 (0.6 – 123.4) 38.5 (1.0 – 214.6)\nPfizer 1-42 days 1 45162 22.1 (0.6 – 123.4) 19.3 (0.5 – 107.3)\nVaccineComparison \ninterval# of \nCases# of \nDoses3Rate Per Million \n(95% CI)Rate per 100,000 PY \n(95% CI)\nGSK 43-84 days 2 301547 6.6 (0.8 – 24.0) 5.8 (0.7 -20.9)\nPfizer 43-84 days 1 41031 24.4 (0.6 – 135.8) 21.2 (0.5 – 118.1)\n1Cases restricted to chart confirmed, Brighton Level 1 -3\n2Vaccines administered 8 -1-23 through 4 -13-24\n3Vaccines administered 8 -1-23 through 3 -2-24Risk interval estimates\nComparison interval estimates\n•Background rate for GBS in persons 60+ years old: 1.4 -3.7 per 100,000 PY  (Sejvar , J., et al. Neuroepidemiol , 2011)\nAtrial Fibrillation Following RSV Vaccination\n--No Statistical Signal --\n24\n25Analysis Parameters Signal Information and Informative Counts Nominal AnalysisSequential\nTest\nOutcome \nEventRisk\nInterval\nDaysComp\nInterval\nDays Vaccine TypeSignaled \nin a\nPrior\nRun1New\nSequential\nAnalysis\nSignal2Events \nin Risk\nIntervalEvents in\nComp\nIntervalAdjusted\nExpected \nEvents in \nRisk\nIntervalAdjusted\nRate\nRatio395%\nConfidence\nInterval42-sided\nP value1-sided P\nvalue5\nAFIB 1-21 43-63 GSK w simul No No 81 75 76.7 1.06 0.75-1.49 0.756 0.411\nGSK wo simul No No 198 232 222.3 0.89 0.72-1.10 0.282 0.871\nPfizer w simul No No 7 15 11.9 0.59 0.21-1.51 0.282 0.910\nPfizer wo simul No No 23 33 38.7 0.59 0.32-1.09 0.093 0.968\n22-42 GSK w simul No No 91 109 106.9 0.85 0.63-1.14 0.282 0.876\nGSK wo simul No No 211 222 209.8 1.01 0.83-1.22 0.954 0.497\nPfizer w simul No No 8 17 13.8 0.58 0.22-1.41 0.238 0.924\nPfizer wo simul No No 25 30 29.9 0.84 0.48-1.46 0.530 0.781\n1-42 43-84 GSK w simul No No 190 155 166.7 1.14 0.90-1.44 0.267 0.146\nGSK wo simul No No 422 441 444.2 0.95 0.82-1.10 0.496 0.764\nPfizer w simul No No 23 27 23.3 0.99 0.54-1.79 0.966 0.577\nPfizer wo simul No No 52 60 71.3 0.73 0.48-1.10 0.137 0.945VSD RCA of RSV Vaccine in Older Adults  \nSurveillance Initiated on 01AUG2023, Analyses Based on Data Through 25MAY2024 (run #6, week #1846) \nConcurrent Comparator Sequential Analysis Signal Assessment for Atrial Fibrillation\n---Age:60+ yrs---\n\n•VSD initiated surveillance in older adults in January 2024\n•385,729 doses of RSV vaccines have been administered to older adults \n(88% GSK)\n•Statistical signal for ITP in persons 60+ years old who received the GSK \nRSV vaccine without simultaneous vaccination\n-Most were not incident ITP cases with onset after RSV vaccination\n-Plan for more detailed chart review of ITP in the fall\n•No GBS signal, but few observed cases\n•No other statistical signals observed to date\n•Surveillance will continue for all outcomes, including GBS, through May \n2025VSD RSV RCA Summary and Next Steps\n26\nRCA Study Team and Acknowledgments\n27•Marshfield Clinic Research Institute: Ed Belongia, Hannah Berger, Kayla \nHanson, Burney Kieke, Dave McClure, Erica Scotty, Maria Sundaram, Jim \nDonahue\n•Centers for Disease Control and Prevention: Eric Weintraub, Tat’Yana \nKenigsberg, Amelia Jazwa , Tanya Myers, Mike McNeil, and Lily Wang\n•Thank you to our colleagues at the other VSD sites: Kaiser Permanente \n(Northern CA, Southern CA, Washington, Northwest, Colorado, Mid -\nAtlantic), Denver Health, HealthPartners, and Harvard Pilgrim\n•Many thanks to our colleagues at Kaiser Permanente Northern California \nfor their assistance with this project and their innovative analytic methods: \nBruce Fireman, Joan Bartlett, Kristin Goddard, Ned Lewis, and Nicky Klein\n28The findings and conclusions in this presentation are those \nof the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention", "summary": "Update: Rapid Cycle Analysis of RSV  Vaccines in Older Adults Jim Donahue, PhD DVM Marshfield Clinic Research Institute Presented to the ACIP June 26, 2024 1 RSV RCA Interim Report – June 26, 2024 •Description of Vaccine Safety Datalink and RCA •Review of surveillance methods •Descriptive analysis •Sequential analysis ̶Immune thrombocytopenia (ITP) ̶Guillain -Barré syndrome (GBS) ̶Atrial fibrillation 2 Vaccine Safety Datalink 2024 * 3•Collaborative project between CDC and 13 integrated…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/05-RSV-Adult-Donahue-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 28}
{"title": "06 RSV Adult Lloyd 508", "content": "1\nEvaluation of Guillain -Barré Syndrome (GBS) \nfollowing Respiratory Syncytial Virus (RSV) \nVaccination Among Adults 65 Years and Older\nDr. Patricia Lloyd, ScM PhD\nHealth Statistician\nOffice of Biostatistics and Pharmacovigilance\nCenter for Biologics Evaluation and Research\nU. S. Food & Drug Administration\nMEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)\nRespiratory Syncytial Virus (RSV) Vaccine, Adults \nJune 26 – 28, 2024\n2\nOutline\n•Introduction\n•Observed vs. Expected Analysis Summary\n▪Study Methods and Results\n•Self-Controlled Case Series (SCCS) Analysis\n▪Study Methods and Results\n•Discussion\n•Conclusion\n3\nIntroduction\n•Two* RSV vaccines were approved for use in the U.S. in adults 60 years and \nolder\n▪RSVPreF3+AS01 (GSK - AREXVY)\n▪RSVPreF (PFIZER - ABRYSVO)\n•An imbalance in the rates of Guillain -Barré syndrome (GBS) between vaccine \nand placebo recipients was identified in clinical trials supporting licensure of \nRSV vaccines 1, 2\n•FDA is conducting a post -licensure RSV vaccine safety study using two designs:\n▪Observed vs. Expected Analysis\n▪Self-Controlled Case Series (SCCS) Analysis\n*mRNA -1345 (Moderna - mRESVIA ®) was approved on May 31, 2024.\n4\nObserved vs. Expected Analysis Summary\nMethods\n•Evaluated risk of GBS following one dose of either RSVPreF3+AS01 \nor RSVPreF vaccines using a retrospective cohort design with the \n2022 historical comparator\n•Estimated the observed incidence rates (IRs) and compared to \nhistorical comparator (expected) rates, to obtain incidence rate \nratios (IRRs) with 95% confidence intervals (CIs)\n•Estimation of GBS positive -predictive value (PPV) -adjusted rates is \nbased on multiple imputed datasets\n▪Chart review, PPV for GBS: 71% (95% CI: 63%, 79%) 3\n5\nObserved vs. Expected Analysis Summary\nResults\nRSVPreF3+AS01 RSVPreF\nInferential Analysis Results \nObserved vs. Expected Analysis 2.76 (95% CI: 1.32, 5.07) 6.94 (95% CI: 3.70, 11.87)\nPPV-Adjusted Analysis 2.75 (95% CI: 0.46, 5.04) 6.91 (95% CI: 1.85, 11.97) \nGBS Cases per 1 million Doses 10.0 25.1 \nDescriptive Analysis Results\nTotal RSV Vaccine Doses 2,061,602\nRSV Vaccine Doses 1,379,335 682,267 \nObserved GBS cases <11 13\nData Through Date: Dec 02, 2023•An elevated IRR was observed for GBS following RSV vaccination\n•Only RSVPreF association was statistically significantly elevated in PPV -adjusted analysis\n6\n•The observed vs. expected analysis is a crude method with \nlimited adjustments for confounding, utilizing aggregate \nhistorical incidence rates rather than individual historical persons \nas comparators, increasing the potential for confounding and \nbias\n•The SCCS is a robust method that controls for time -invariant \nconfounding and does not rely on historical background \nincidence ratesMotivation for SCCS Study\n7\nSelf-Controlled Case Series (SCCS) Design\n•Population Exclusion Criteria: \n▪Beneficiaries with no incident \nGBS outcome in the \nobservation period \nOR\n▪Beneficiaries who do not \nmeet criteria to identify an \nincident outcome**\nDays  43-90 Days 1 -42\n365 Days Prior\nStudy Start Date\nMay 2023Study End Date\nApr 2024\nRSV Vaccination (Day 0)= Risk Interval\n= Control Interval\n= GBS Outcome\n*The clean window is relative to the outcome date; risk and control intervals are relative to the vaccination date\n**Outcomes that are considered ‘incident’ after implementing the outcome -specific cleaning window are included, \nand only first incident outcome in the observation period are retained•Population Inclusion Criteria: \n▪Enrolled in Medicare Fee -\nfor-Service (FFS) during the \nclean window\n▪65 years of age or older on \nRSV vaccination date\n▪No GBS outcome during the \nclean window= Clean Window (365 days)*\n8\nSCCS Analysis: Study Methods\nStudy Design Self-Controlled Case Series (SCCS) 4, 5\nData Sources and \nStudy PopulationCenters for Medicare & Medicaid Services (CMS)  Medicare Beneficiaries ages 65 years \nand older, enrolled in:\n▪Medicare FFS (Parts A and B) and Part D on the date of RSV vaccination\n▪Medicare FFS and in 1 -year prior\nStudy Period May 2023* – April 2024 ⬧**\nGBS Outcome \nDefinition▪Risk Interval: 1 - 42 days\n▪Control Interval: 43 - 90 days\n▪Care Setting: inpatient – primary position only; ICD -10-CM DGN G61.0\nStatistical \nAnalyses▪IRRs with 95% CIs\n▪Absolute Risk: Attributable Risk (AR) with 95% CIs per 100,000 doses and 100,000 \nperson -years (PY)\n▪Adjustment for outcome -dependent observation time (Farrington) 6, seasonality, PPV\n*FDA approval dates for RSVPreF3+AS01 and RSVPreF were May 3, 2023 and May 31, 2023, respectively\n⬧Study end date for initial SCCS analysis was April 6, 2024\n**RSV vaccinations prior to October 8, 2023 to have complete observation in 90 days post -vaccination and is expected to have 90%  or greater data -completeness\n9\nSCCS Analysis: Vaccination Uptake Trends\n020,00040,00060,00080,000100,000120,000140,000160,000180,000200,000Number of RSV Vaccinations\nCalendar WeekWeekly Vaccination Uptake Trends in RSV Vaccines, By Vaccine Type\nRSVPreF RSVPreF3+AS01\n Vaccination Cut -off Date to ensure complete observation of 90 -day window\nData Through Date: Apr 06, 2024\n10\nCase Population Eligibility \nCriteriaRSV Vaccinations\n(n=1.33 M individuals; 1.33 M doses)*\nRSVPreF3+AS01 \n(n= ~872k doses)*RSVPreF\n(n= ~456k doses)*\nTotal GBS cases and total number \nof days in study period160 cases [339 days] 92 cases [311 days]\nGBS cases  during 90 -day \nobservation period 105 74\nIncident GBS cases after applying \nclean window restriction55 36\nGBS cases qualifying for SCCS \nanalysis\n(vaccinated before Oct 8, 2023)11 17Case Counts for GBS following RSV vaccination by Vaccine Type\n* n = Medicare Beneficiaries that received RSV vaccination and eligible for SCCS analysis are presentedSCCS Analysis: Descriptive Results\nData Through Date: Apr 06, 2024\n11\n Data Through Date: Apr 06, 2024SCCS Analysis: Results for GBS\nMost Adjusted \nAnalysis\nLeast\nAdjusted \nAnalysis\nSCCS Analysis including most adjustments are highlighted in Blue\nFarrington -Adjusted Analysis = Outcome -Dependent Observation Time AdjustmentIRR with 95% CI of GBS following RSV Vaccination Adjusted for Combinations of PPV, \nSeasonality with Outcome -Dependent Observation Time\n•An elevated IRR was observed for GBS following RSVPreF vaccination with two analyses that had the least adjustments\n•Results additionally adjusted for PPV were no longer statistically significant\n▪PPV, Seasonality with Farrington -Adjusted Analysis: 4.48 (95% CI: 0.88, 22.90) ▪PPV, with Farrington -Adjusted Analysis: 3.96 (95% CI: 0.77, 20.28) \nSeasonality, \nFarrington\nFarringtonPPV, FarringtonPPV, Seasonality, \nFarringtonAnalyses\n12\nSCCS Analysis: Results for GBS and                         \nRSV vaccination\nInferential Analysis Results RSVPreF3+AS01 RSVPreF\nEligible Vaccinees 872,068 456,107\nCases in the Risk and Control \nIntervals<11 12.1\nIRR (95% CI) 2.30 (0.39, 13.72) 4.48 (0.88, 22.90)\nAR per 100,000 Doses (95% CI) 0.32 ( -0.30, 0.95) 1.57 (0.30, 2.85)\nAR Per 100,000 PY (95% CI) 2.81 ( -2.64, 8.26) 13.69 (2.59, 24.79)Incidence Rate Ratio (IRR) and Attributable Risk (AR) of GBS - Adjusted for PPV, Seasonality and \nOutcome -Dependent Observation Time\nData Through Date: Apr 06, 2024\n13\n•SCCS study design provides \nrobust adjustment for potential \ntime-invariant confounding\n•Large database facilitates \nmore precise evaluation of \nhealth outcomes\n•Study findings are \ngeneralizable to U.S. \npopulation 65 years and olderDiscussion\nStrengths Limitations\n•Potential outcome \nmisclassification \n•Potential misspecification of \nrisk and control intervals\n•Potential for residual \nconfounding\n14\nDiscussion\nObserved vs. Expected Analysis\n•An elevated IRR was observed for GBS following RSV vaccination, \nbut only RSVPreF association was statistically significantly elevated \nPPV (chart review) adjustment\n•Crude method that utilized aggregate historical comparator rates \nrather than individuals, increasing the potential for confounding\n•Statistically significant results of GBS do not establish a causal \nassociation between RSV vaccines and GBS\n15\nDiscussion\nSCCS Analysis\n•Although, an elevated IRR was observed for GBS following \nRSVPreF vaccination for two analyses that had fewer adjustments, \nthe results were not statistically significant when adjusted for PPV\n•Only cases, i.e., persons with an incident outcome contribute to the \nSCCS analysis\n•Estimation of outcome risk occurs within, rather than between \nindividuals, adjusting for time -invariant confounding\n16\nConclusion\n•The results from two different types of analyses of potential GBS risk \nfollowing RSV vaccination are mixed and highly uncertain\n•These analyses do not provide clear, conclusive evidence of an elevated \nrisk of GBS and an elevated risk cannot be ruled out at this time\n•FDA is conducting medical chart review on GBS cases and will continue to \nevaluate the safety of RSV vaccines as more data are available\n•FDA maintains that the b enefits of RSV vaccination in preventing RSV \nhospitalizations outweigh the potential risks associated with the vaccines\nReferences\n17\n1.Respiratory Syncytial Virus Vaccine Recombinant, Adjuvanted ( Arexvy ). Vaccines and Related Biological \nProducts Advisory Committee Meeting. FDA Briefing Document. March 1, 2023. \nhttps://www.fda.gov/media/165622/download\n2.Respiratory Syncytial Virus Stabilized Bivalent Prefusion F Subunit Vaccine ( Abrysvo ). Vaccines and \nRelated Biological Products Advisory Committee Meeting. FDA Briefing Document. March 1, 2023. \nhttps://www.fda.gov/media/165625/download\n3.Arya,D.P ., et al. Surveillance for Guillain -Barré syndrome after 2015 -2016 and 2016 -2017 influenza \nvaccination of Medicare beneficiaries. Vaccine, 2019. 37(43): p. 6543 -6549.\n4.Petersen I, Douglas I, Whitaker H. Self controlled case series methods: an alternative to standard \nepidemiological study designs. 2016;354:i4515. \n5.Evaluation of Multiple Safety Outcomes following RSV Vaccination in Adults 60 Years and Older. \nhttps://bestinitiative.org/wp -content/uploads/2024/01/BEST_RSV_Safety_Older_Adults_2023 -2024.pdf\n6.Farrington, C. P., Anaya -Izquierdo , K., Whitaker, H. J., Hocine , M. N., Douglas, I., & Smeeth, L. (2011). Self -\nControlled Case Series Analysis With Event -Dependent Observation Periods. Journal of the American \nStatistical Association, 106(494), 417 –426. https://doi.org/10.1198/jasa.2011.ap10108\nAcknowledgements\n18\nSteven Anderson\nRichard Forshee\nNarayan Nair\nJoann Gruber\nCarla Zelaya\nTainya Clarke\nFDA Partners: \nAcumen, CMS\nQuestions?\n19", "summary": "1 Evaluation of Guillain -Barré Syndrome (GBS)  following Respiratory Syncytial Virus (RSV)  Vaccination Among Adults 65 Years and Older Dr. Patricia Lloyd, ScM PhD Health Statistician Office of Biostatistics and Pharmacovigilance Center for Biologics Evaluation and Research U. S. Food & Drug Administration MEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP) Respiratory Syncytial Virus (RSV) Vaccine, Adults  June 26 – 28, 2024 2 Outline •Introduction •Observed vs. Expected…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/06-RSV-Adult-Lloyd-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 19}
{"title": "07 RSV Adult Surie 508", "content": "Effectiveness of adult respiratory syncytial virus (RSV)  \nvaccines, 2023 –2024\nDiya Surie, MD\nCoronavirus and Other Respiratory Viruses Division\nCenters for Disease Control and Prevention\nJune 26, 2024National Center for Immunization and Respiratory Diseases\nThis presentation has been \ncorrected. See slides 5, 6, 30, \nand 32 for corrected slides. The \noriginal slides are included at \nthe end of the presentation.\n•Purpose of randomized vaccine trials is to answer the question:Goal of randomized vaccine trials is different from that \nof observational vaccine effectiveness (VE) studies\nClemens J, et. al. Evaluating New Vaccines for Developing Countries: Efficacy or Effectiveness? JAMA.  1996;275(5) 390 –397. doi:10.1001/jama.1996.03530290060038 “Can the vaccine reduce disease caused by the target infection, safely, \nunder ideal conditions designed to detect a protective effect?”\n•To maximize chances of detecting a protective effect, vaccine trials often:\n-Enroll healthy individuals in the target population\n-Minimize or exclude enrollment of individuals with comorbidities that might reduce \nimmuno genicity of vaccines\n•Post -licensure observational VE studies are needed to assess vaccine performance in a \nheterogeneous  population under routine vaccine program conditions\nLimitations of RSV vaccine trials\n1Papi A, et al; AReSVi -006 Study Group. Respiratory syncytial virus prefusion F protein vaccine in older adults. N Engl J Med . 2023;388(7):595 -608\n2Walsh EE, et al; RENOIR Clinical Trial Group. Efficacy and safety of a bivalent RSV prefusion F vaccine in older adults. N Engl J Med . 2023;388(16):1465 -1477\n3Critical illness is defined as intensive care unit admissions or deathRandomized \nRSV vaccine trials1,2Observational \nRSV VE studies\nImmunocompromised patients Excluded Included\nAdults aged ≥80 years <8% of participants ≥25% of included adults\nAny chronic condition <52% of participants ≥94% of included adults\nEndpoint or outcome Symptomatic, RSV -\nassociated lower \nrespiratory tract \ndiseaseRSV-associated emergency \ndepartment (ED) visits , \nhospitalization , critical \nillness3\nPresentation outline for observational VE studies\nObservational VE studies Methods\nIVY Network (CDC) Test-negative design1,2,3\nVISION (CDC)\nVeterans Health Administration (VHA) Target trial emulation4,5\nMedicare/end stage renal disease (ESRD) patients Retrospective cohort\nReferences for study design methods with relevant examples\n1 Chua H, et. al. The Use of Test -negative Controls to Monitor Vaccine Effectiveness: A Systematic Review of Methodology. Epidemiology  2020;31:43 –64.\n2 Adams K, et. al.  Vaccine effectiveness of primary series and booster doses against COVID -19-associated hospital admission in t he United States. BMJ  2022;379:e072065. \n3 Thompson MG, et. al. Effectiveness of COVID -19 Vaccines in Ambulatory and Inpatient Care Settings. N Engl J Med. 2021;385:1355 –1371.\n4 Hernan MA, et. al. Methods of Public Health Research – Strengthening Causal Inference from Observational Data. N Engl J Med. 202 1;385(15):1345 –48.  \n5 Bajema KL, et. al. Effectiveness of COVID -19 Treatment with Nirmatrelvir -Ritonavir or Molnupiravir  Among U.S. Veterans. Ann Intern Med. 2023;176(6):807 –816. \nComparison of demographic characteristics among \nIVY , VISION, VHA, and Medicare/ESRD studies\nIVY , \nno. (col %)VISION , \nno. (col %)VHA , \nno. (col %)Medicare/ESRD , \nno. (col %)\nCharacteristic Total no. \nof\npatientsTotal no. \nof\npatientsTotal no. \nof\npatientsTotal no. \nof\npatients\nAll patients 2,978 36,706 293,704§69,279\nMedian age, years (IQR) 72 (66 –80) 76 (69 –84) 76 (72 –80) 75 (70 -80)\nAge group, years\n60–74 1756 (59) 16,055 (44) 125,124 (43) 34,614 (50)‡\n≥75 1222 (41) 20,651 (56) 168,580 (57) 34,665 (50)\nRace and ethnicity\nWhite, non -Hispanic 1867 (63) 27,057 (74) 225,713 (77) 42,157 (61)\nBlack, non -Hispanic  582 (20) 3,160 (9) 30,359 (10) 14,767 (21)\nHispanic or Latino, any race 335 (11) 2,789 (8) 11,302 (4) 3,983 (6)\nOther race, non -Hispanic*101 (3) 3,395 (9) 5,971 (2) 8,372 (12)\nUnknown†93 (3) 305 (1) 20,358 (7) -\n* For VISION, “Other race, non -Hispanic” includes persons reporting non -Hispanic ethnicity and any of the following for race: Am erican Indian or Alaska Native, Asian, Native Hawaiian or other Pacific Islander, \nother races not listed, and multiple races; because of small numbers, these categories were combined. For IVY, “Other race, n on-Hispanic” includes Asian, American Indian or Alaska Native, and Native Hawaiian \nor other Pacific Islander; because of small numbers, these categories were combined. For Medicare/ESRD, \"Other race, non -Hispani c\" includes Asian/Pacific Islander, non -Hispanic, Other, non -Hispanic, and \nUnknown.\n† For VISION, “Unknown” includes persons with missing race and ethnicity in their electronic health records. For IVY, “Unknow n” includes patients who self -reported their race and ethnicity as “Other” and those \nfor whom race and ethnicity were unknown. For VHA “Unknown” includes missing, unknown, or declined race or ethnicity.\n§146,852 vaccinated persons were matched to 582,936 unvaccinated participants who were equally weighted to correspond to 146,8 52 matched unvaccinated participants. \n‡Evaluation of Medicare fee -for-service claims data was restricted to adults aged 65 years and older.This slide contains corrections. To see the slide as originally presented, without corrections, please see slide 45. \nComparison of clinical characteristics among IVY , \nVISION, VHA, and Medicare/ESRD studies\nIVY , \nno. (col %)VISION , \nno. (col %)VHA , \nno. (col %)Medicare/ESRD , \nno. (col %)\nCharacteristic Total no. \nof\npatientsTotal no. \nof\npatientsTotal no. \nof\npatientsTotal no. \nof\npatients\nAll patients 2,978 36,706 293,704 69,279\nNo. of chronic medical condition categories\n0 71 (2) 2,111 (6) 17,554 (6) 0 (0)\n1 416 (14) 3,845 (10) 58,757 (20) 312 (<1)\n2 783 (26) 15,420 (42) 83,992 (29) 1,497 (2)\n3 863 (29) 15,330 (42) 73,296 (25) 9,242 (13)\n≥4 845 (28) 2,111 (6) 60,106 (21) 58,228 (84)\nImmunocompromised*720 (24) 8,435 (23) 32,996 (11) 17,499 (25)\nChronic lung disease†1423 (48) 17,541 (48) 88,648 (30) 38,529 (56)\nCardiovascular disease§2501 (84) 28,822 (79) 122,015 (42) 66,987 (97)\nRSV vaccinated 265 (9) 3,275 (9) 146,852 (50)¶6,731 (10)\nReceived GSK (Arexvy) 137 (61)** 2,409 (74) 43,875 (30) 4,559 (68)\nReceived Pfizer (Abrysvo) 89 (39) ** 865 (36) 101,623 (69) 2,172 (32)\n* Slide 41 provides definitions of immunocompromise from each network\n† Slide 42 provides definitions of chronic lung disease from each network\n§ Slide 43 provides definitions of cardiovascular disease from each network\n¶ Each RSV -vaccinated patient was matched to up to 4 unvaccinated, equally weighted patients, resulting in 50% of matched persons having an RSV vaccination. Among match -eligible patients, 4.5% received RSV vaccination.\n** Of 265 RSV vaccinated patients in IVY, 226 (85%) had known product type, which is used as the denominator for these percentag es.This slide contains corrections. To see the slide as originally presented, without corrections, please see slide 47. \nVE against RSV -associated hospitalization \namong adults aged ≥60 years\nIVY Network, October 1, 2023 –March 31, 2024\nIVY Network —26 hospitals, 20 U.S. States\n•Design : Test -negative, case -control design\n•Analysis period : October 1, 2023 – March 31, 2024\n•Population : Adults  aged  ≥60 years  hospitalized with acute respiratory \nillness (ARI)* and RSV test results within 10 days of illness onset and 3 days \nof admission\n•Cases : ARI and test  positive  for RSV by NAAT or antigen test\n– Co-infections with SARS -CoV-2 or influenza were excluded\n• Controls : ARI and test negative  for vaccine -preventable respiratory \nviruses, i.e., RSV, SARS -CoV-2 and influenza by RT -PCR†\n•Vaccination data: Plausible self -report, e lectronic medical records (EMR), \nstate and city vaccine registries\n•Vaccinated: Receipt of a single dose of either RSV vaccine (GSK or \nPfizer) ≥14 days before illness onset\n•Unvaccinated : No RSV vaccination before illness onset\n•Specimens: Nasal swabs  obtained on all patients for central RT -PCR testing \nand whole genome sequencing\n*ARI is defined as presence of any one of the following: fever, cough, shortness of breath, chest imaging consistent with pne umo nia, or hypoxemia ( SpO2 <92% on room air or below baseline for chronic users)\n† Doll MK, et. al. Effects of Confounding Bias in Coronavirus Disease 2019 (COVID -19) and Influenza Vaccine Effectiveness Test -Negative Designs Due to Correlated Influenza and COVID -19 Vaccination Behaviors. \nClin Infect Dis. 2022;75(1):e564 –71 \n\nVE against RSV -associated hospitalization  among adults aged ≥60 years — \nIVY Network, 24 hospitals, 19 US states, October 1, 2023 –March 31, 2024\nAbbreviations : 95% CI = 95% confidence interval; IPVW = inverse probability of vaccination weighting; IQR = interquartile range\n* Logistic regression m odels  were adjusted for age, sex, race and ethnicity, U.S. Department of Health and Human Services region, and month of admission. VE was calculated as: (1 – adjusted odds ratio) x 100%.\n† For the IPVW VE estimate, propensity for vaccination was modeled with a priori  covariables,  including age, sex, race and ethnicity, site, calendar month, Charlson  Comorbidity Index (CCI), underlying medical \nconditions, long -term care facility residence, numbers of outpatient visits or hospitalizations in the previous year, and social  vulnerability index (SVI) of community of residence. Weights were computed as the \ninverse of the probability of vaccination. Only SVI remained unbalanced between vaccinated and unvaccinated patients after weigh ting and was included as a covariate in the final logistic regression model.GroupNo. of \nvaccinated RSV \ncase -patients/        \ntotal (%)No. of \nvaccinated RSV \ncontrol -\npatients/\ntotal  (%)Days since RSV \nvaccination, \nMedian (IQR)Vaccine \neffectiveness,    \n% (95% CI)\nAdults ≥60 years, unweighted* 9/367 (2.5) 256/2611 (9.8) 84 (54 –125) 75 (50 –87)\nAdults ≥60 years, IPVW†9/367 (2.5) 256/2611 (9.8) 84 (54 –125) 79 (56 –90)\nAge group, years, unweighted*\n60–74 years 4/214 (1.9) 118/1542 (7.7) 88 (57 –128) 75 (31 –91)\n≥75 years 5/153 (3.3) 138/1069 (12.9) 81 (50 –123) 76 (40 –91)\n0 20 40 60 80 100\nVaccine Effectiveness, % (95% CI) VE was high against RSV -associated \nhospitalization and similar among adults \naged 60 –74 years and ≥75 years\nVE against RSV -associated ED visits, \nhospitalization, and critical illness among \nadults aged ≥60 years\nVISION Network, October 1, 2023 –March 31, 2024 \n•Design:  Test-negative design analysis\n•Population:  Adults aged ≥60 years visiting a participating ED \nfor or hospitalized with RSV -like illness (RLI)* with RSV test \nresult within 10 days before or 72 hours after encounter\n-Cases:   RLI with positive  RSV antigen or NAAT\n-Controls:   RLI with negative RSV NAAT\n•Vaccination data:  Documented by electronic health records, \nstate and city registries, and claims data (subset of sites)\n-Vaccinated: Receipt of a single dose of either RSV vaccine (GSK or Pfizer) ≥14 \ndays before illness onset\n-Unvaccinated : No RSV vaccination before illness onset\n•Covariate data:  Documented in electronic health recordsVISION Multi -Site Network of Electronic Health Records\n245 emergency rooms and 230 hospitals\nVISION 2.0 partners included in this analysis – \nED: HealthPartners Institute, Intermountain Healthcare, KPNC, KPCHR, \nRegenstrief\nInpatient : HealthPartners Institute, Intermountain, KPNC, KPCHR, Regenstrief , \nUniversity of Colorado\n• Note: KPSC does not participate in VISION adult RSV analyses.\n*≥1 ICD -10 code indicating RSV -like illness (RLI), defined as COVID -19 pneumonia, influenza pneumonia, other viral pneumonia, in fluenza disease, bacterial pneumonia, ARDS, COPD \nexacerbation, asthma exacerbation,  respiratory failure, other acute lower respiratory tract infection, sinusitis, acute uppe r respiratory tract infections, acute respiratory signs and symptoms, \nviral illness not otherwise specified, acute febrile illness signs and symptoms, sepsis, respiratory failure unspecified, and  RSV disease.\nVE against RSV -associated ED visits , hospitalization , and critical illness among \nimmunocompetent  adults aged ≥60 years, October 1, 2023 –March 31, 2024\nTotalRSV -Positive, \nN (row %)Median interval \nsince last dose, \ndays (IQR)Vaccine \nEffectiveness*, \n% (95% CI)\nRSV -associated ED visits\n≥60 years\nUnvaccinated (Ref) 33,491 2,645 (8) NA Ref\nVaccinated 3,030 57 (2) 67 (40 –101) 77 (70 –83)\nRSV -associated hospitalization\n≥60 years\nUnvaccinated (Ref) 25,816 1567 (6) NA Ref\nVaccinated 2,455 35 (1) 74 (44 –109) 80 (71 –85)\nRSV -associated critical Illness†\n≥60 years\nUnvaccinated (Ref) 24,506 257 (1) NA Ref\nVaccinated 2,425 5 (<1) 74 (44 –109) 81 (52 –92)\n0 20 40 60 80 100\nVaccine Effectiveness, % (95% CI)\n*Odds ratios used to calculate VE estimates were adjusted for age, race/ethnicity, sex, underlying medical conditions, social  vulnerability index, site, calendar time, and \ngeographic region. VE was calculated as (1 -adjusted odds ratio)*100%.\n† Critical illness was defined as intensive care unit admission and/or deathVE was high against RSV -associated ED \nvisits, hospitalization, and critical illness\nVE against RSV -associated ED visits and hospitalization  by age group among \nimmunocompetent  adults aged ≥60 years, October 1, 2023 –March 31, 2024\nTotalRSV -Positive, \nN (row %)Median interval \nsince last dose, \ndays (IQR)Vaccine \neffectiveness*,\n % (95% CI)\nRSV -associated ED visits\n60–74 years\nUnvaccinated (Ref) 16,985 1303 (8) NA Ref\nVaccinated 1,139 23 (2) 66 (40 –100) 75 (62 –84)\n≥75 years\nUnvaccinated (Ref) 16,506 1342 (8) NA Ref\nVaccinated 1,891 34 (2) 69 (40 –101) 78 (69 –85)\nRSV -associated hospitalization\n60–74 years\nUnvaccinated (Ref) 11,048 670 (6) NA Ref\nVaccinated  836 11 (1) 75 (46 –110) 81 (66 –90)\n≥75 years\nUnvaccinated (Ref) 14,768 897 (6) NA Ref\nVaccinated 1,619 24 (1) 74 (43 –108) 79 (68 –86)\n0 20 40 60 80 100\nVaccine Effectiveness, % (95% CI)\n* Odds ratios used to calculate VE estimates were adjusted for age, race/ethnicity, sex, underlying medical conditions, socia l vulnerability index, site, calendar time, and \ngeographic region. VE was calculated as (1 -adjusted odds ratio)*100%.VE was similar among adults aged 60 –74 \nyears and ≥75 years for both outcomes\nVE against RSV -associated ED visits and hospitalization  by time since RSV vaccination \namong immunocompetent  adults aged ≥60 years, October 1, 2023 –March 31, 2024\nTotalRSV -Positive, \nN (row %)Median interval \nsince last dose, \ndays (IQR)Vaccine \neffectiveness*,    \n% (95% CI)\nRSV -associated ED visits\n≥60 years\nUnvaccinated (Ref) 33,491 2,645 (8) NA Ref\nVaccinated 14 –59 days earlier 1,300 19 (1) 36 (26 –47) 85 (77 –91)\nVaccinated 60 –215 days earlier 1,728 37 (2) 95 (76 –119) 70 (58 –78)\nRSV -associated hospitalization\n≥60 years\nUnvaccinated (Ref) 25,816 1567 (6) NA Ref\nVaccinated 14 –59 days earlier  934 7 (1) 37 (26 –48) 90 (79 –95)\nVaccinated 60 –215 days earlier 1,520 27 (2) 100 (79 –125) 73 (60 –82)\n0 20 40 60 80 100\nVaccine Effectiveness, % (95% CI)VE point estimates decreased with \nincreased time since RSV vaccination with \nlimited follow -up time within the season\n* Odds ratios used to calculate VE estimates were adjusted for age, race/ethnicity, sex, underlying medical conditions, socia l vulnerability index, site, calendar time, and \ngeographic region. VE was calculated as (1 -adjusted odds ratio)*100%.\nVE against RSV -associated ED visits and hospitalization  by RSV vaccine manufacturer \namong immunocompetent  adults aged ≥60 years, October 1, 2023 –March 31, 2024\notalRSV -Positive, \nN (row %)Median interval \nsince last dose, \ndays (IQR)Vaccine \neffectiveness*,    \n% (95% CI)\nRSV -associated ED visits\n≥60 years\nUnvaccinated (Ref) 33,491 2,645 (8) NA Ref\nGSK (Arexvy) 2,522 47 (2) 67 (40 –99) 77 (70 –83)\nPfizer ( Abrysvo )  506 9 (2) 71 (40 –108) 79 (59 –89)\nRSV -associated hospitalization\n≥60 years\nUnvaccinated (Ref) 25,816 1567 (6) NA Ref\nGSK (Arexvy) 1,812 21 (1) 73 (43 –105) 83 (73 –89)\nPfizer (Abrysvo)  642 13 (2) 81 (48 –116) 73 (52 –85)\n0 20 40 60 80 100\nVaccine Effectiveness, % (95% CI) VE was similar between GSK and \nPfizer RSV vaccines across outcomes\n* Odds ratios used to calculate VE estimates were adjusted for age, race/ethnicity, sex, underlying medical conditions, socia l vulnerability index, site, calendar time, and \ngeographic region. VE was calculated as (1 -adjusted odds ratio)*100%.\nVE against RSV -associated hospitalization  among adults aged ≥60 years with \nimmunocompromise† by age group, October 1, 2023 –March 31, 2024\n0 20 40 60 80 100\nVaccine Effectiveness, % (95% CI)\n*Odds ratio was adjusted for age, race/ethnicity, sex, underlying medical conditions, social vulnerability index, site, calen dar time, and geographic region. VE was \ncalculated as (1 -adjusted odds ratio)*100%.\n†Defined based on presence of ICD -10 code corresponding to hematologic malignancy, solid malignancy, transplant , rheumatologic/inflammatory disorders, HIV, or other \nintrinsic immune condition or immunodeficiency in discharge diagnoses TotalRSV -Positive, \nN (row %)Median interval \nsince last dose, \ndays (IQR)Vaccine \neffectiveness*,     \n% (95% CI)\nRSV -associated hospitalization\n≥60 years\nUnvaccinated (Ref) 7,615 314 (4) NA Ref\nVaccinated 820 10 (1) 72 (43 –108) 73 (48 –85)\nRSV vaccines provided protection against \nRSV-associated hospitalization among \npeople with immunocompromise\nVE against documented RSV infection and RSV -\nassociated ED/UC or hospitalization among \nadults aged ≥60 years \nVeterans Health Administration (VHA), September 1, 2023 – March 31, 2024\nOverall study design\n▪Emulated a target randomized controlled trial of RSV vaccination (GSK [ Arexvy ] or Pfizer \n[Abrysvo ]) compared with no RSV vaccination for the prevention of documented RSV infection and \nRSV-associated ED/urgent care (UC) visits or hospitalization among Veterans ≥60 years\n▪Enrollment: September 1 – December 31, 2023\n▪Follow -up extended through March 31, 2024\n▪Executed 4 monthly, nested sequential trials during the enrollment period\nNested sequential trial study design with matching\nMarch 31, 2024\nAbbreviations: CAN, Care Assessment Need; VISN, Veteran Integrated Service Network\n* Cohort members who receive an RSV vaccine during a given trial month are no longer eligible for a subsequent trial month. C ohort members who remain unvaccinated, \nalive, and who do not test positive for RSV through the end of a given trial month are eligible for a subsequent trial month.  \n† Follow -up begins on the day following the index date (date of RSV vaccination occurring anytime during a given trial month or same date for the matched unvaccinated \ncomparator) and extends until occurrence of the outcome, death, or end of the study period on March 31, 2024. \nData sources\n▪The Department of Veterans Affairs \nCorporate Data Warehouse (CDW) \nintegrates real -time, electronic health \nrecord (EHR) data across all VHA \nfacilities\n▪RSV tests were performed on \nrespiratory specimens within VHA \nusing nucleic acid amplification or \nantigen testing\n▪RSV vaccinations were administered \nat VHA facilities or outside facilities \nand recorded in the VHA EHR\nVHA Network\n18 regional systems of care\n172 medical centers\n1,138 outpatient sites of carehttps://www.va.gov/HEALTH/visns.asp\nEligibility\n▪VHA enrollees ≥60 years during September 1 – December 31, 2023\n▪Engaged in VHA care: ≥1 primary care encounter within 18 months prior to the first day of each \ntrial month\n▪Excluded: \n▪Missing ZIP codes\n▪Any RSV vaccination prior to the first day of each trial month\n▪Any positive RSV test results in the 90 days preceding the start of each trial month\nOutcomes, Follow -up, and Analysis\n▪Outcomes\n▪Primary outcome:  Any positive RSV test result occurring from day 14 following the index date \nthrough the end of the study period on March 31, 2024*\n▪RSV-associated emergency department (ED) or urgent care encounters (UC)†\n▪RSV-associated acute hospitalizations†\n▪Negative outcome control:  incidence of laboratory -confirmed RSV infections 0 –13 days following \nthe index date\n▪Vaccine effectiveness = (1 – hazard ratio) x 100\n*Primary analysis is limited to matched groups in which patients did not have a positive RSV test result during days 0 –13 follow ing the index date.\n†Occurring ±1 day of the eligible positive RSV test result.\nCumulative incidence of documented RSV infections and associated healthcare \nevents following the matched index date, September 1, 2023 –March 31, 2024\nNegative \nOutcome ControlDocumented RSV \nInfection\nRSV-associated \nAcute \nHospitalizationRSV-associated \nED or UC \nEncounter\n\nVE against documented RSV infection and RSV -associated \nED/UC visit or hospitalization, intention to treat*\nRSV vaccination (GSK or Pfizer)\n(N = 146,747)No Vaccination\n(N = 146,747)\nNo. of \nEventsFollow -up \n(person -years)Incidence Rate \n(events / 1000 \nperson -years)No. of \nEventsFollow -up \n(person -years)Incidence Rate \n(events / 1000 \nperson -years)Vaccine \nEffectiveness,\n% (95% CI)\nDocumented RSV \ninfection from 14 \ndays after index date88 51,281 1.7 (1.4 –2.1) 372.0 50,911 7.3 (6.6 –8.1) 77 (71 –81)\nRSV-associated ED or \nUC visit66 51,286 1.3 (1.0 –1.6) 289·3 50,929 5.7 (5.1 –6.4) 77 (71 –82)\nRSV-associated \nhospitalization15 51,298 0.3 (0.2 –0.5) 80·3 50,975 1.6 (1.3 –2.0) 82 (69 –89)\n*Median follow -up 124 days [IQR 102 to 150 days]\nVE against documented RSV infection by age and immunocompromised* \nsubgroups\nRSV Vaccination (GSK or Pfizer) No Vaccination\nNNo. of \nEventsFollow -up, \nperson -\nyearsIncidence \nRate (events/ \n1000 person -\nyears)No. of \nEventsFollow -\nup, \nperson -\nyearsIncidence \nRate (events/ \n1000 person -\nyears)Vaccine \nEffectiveness, \n% (95% CI)\nAge group\n 60–69 years 28,247 17 7,4942.3 \n(1.3–3.6) 74.9 7,47410.0 \n(7.9–12.4) 78 (63 –86)\n 70–79 years 82,734 47 22,2512.1 \n(1.6–2.8) 204.8 22,1689.2 \n(8.0–10.6) 77 (69 –83)\n ≥80 years 35,691 26 9,6012.7 \n(1.8–4.0) 93.5 9,5009.8 \n(8.0–12.0) 72 (59 –81)\nImmunocompromised*\nNo135,936 71 365541.9 \n(1.5–2.5) 325.5 36,3549.0 \n(8.0–10.0) 78 (72 –83)\nYes10,639 16 27535.8 \n(3.3–9.4) 54.2 2,73019.9 \n(15.2 –25.8) 71 (52 –83)\n*Immunocompromised was defined as receipt o f immunosuppressive (excluding steroids) or cancer medications within 90 days or 1 year of the index date (depending on the m edication), HIV with most \nrecent CD4 ≤2 years prior to index date ≤200 cells/mm3, or hematologic malignancy documented ≤2 years prior to index date. \nVE against documented RSV infection by RSV vaccine manufacturer\nRSV vaccination No Vaccination\nNNo. of \nEventsFollow -up, \nperson -\nyearsIncidence \nRate \n(events/ \n1000 \nperson -\nyears)No. of \nEventsFollow -\nup, \nperson -\nyearsIncidence \nRate (events/ \n1000 person -\nyears)Vaccine \nEffectiveness,\n % (95% CI)\nVaccine product\nGSK (Arexvy) 43,853 22 13,4111.6 \n(1.0–2.5) 94 13,3267.1 \n(5.7–8.6) 77 (64 –85)\nPfizer (Abrysvo) 101,542 66 25,5052.6 \n(2.0–3.3) 281·2 25,37611.1 \n(9.9–12.4) 77 (70 –82)\nVE against RSV -associated hospitalization \namong adults aged ≥65 years with end stage \nrenal disease (ESRD)\nCMS Medicare Claims data, October 1, 2023 –February 24, 2024\nData source: Rebecca C. Woodruff, PhD. Chronic Conditions as Risk Factors for RSV -Associated Hospitalization. ACIP Meeting. February 29, 2024 . Available at: \nhttps://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2024 -02-28-29/03 -RSV-Adults -Woodruff -508.pdf     Adults with chronic kidney disease had a higher rate of \nRSV-associated hospitalizations compared with all adults\n*Data sources included Medicare Enrollment Database (EDB) and Common Medicare Environment (CME), Common Working File (CWF) an d Shared System Data (SSD) Medicare Parts A/B/D claims data, Minimum Data Set (MDS), and CDC/ATSDR Social Vulnerability \nIndex (SVI)\n†At least 1 dialysis encounter (excluding acute kidney injury) in the 90 days before the index date (persons with end stage re nal disease receiving dialysis are eligible for Medicare benefits, regardless of age).  Investigation was underpowered to estimat e VE among \npersons aged 60 -64 years with ESRD.\n‡Record of receipt of RSV vaccine dose versus no recorded receipt of RSV vaccine dose using administration codes listed on cla ims data.  Beneficiaries were considered “vaccinated” ≥14 days after the date of vaccine dose administration.\n§ RSV hospitalizations identified from Medicare claims data using International Classification of Diseases, Tenth Revision, Cli nical Modification (ICD -10 CM) diagnosis code specific to RSV (J20.5, J21.0, or B97.4) listed on at least one inpatient facility cl aim in the primary \nposition OR a code specific to RSV pneumonia  (J12.1, ) in any position OR a code specific to RSV in any position paired with  pneumonia or acute respiratory failure outcome code\n¶Death, disenrollment in Medicare parts A/B/D, enrollment in Medicare Part C, nursing home stay lasting ≥100 days, admission t o hospice facility, kidney transplant, receipt of a second RSV vaccine dose\n**Hazard ratios adjusted for sex, age group, race, social vulnerability index (SVI), 2022 -2023 influenza vaccination status, and  Updated (2023 -2024 Formula) COVID -19 vaccination status.Medicare/ESRD: Overview\n• Design: Retrospective cohort\n• Data source:  Medicare fee -for-service claims data*\n• Population:  Persons aged ≥65 with ESRD†\n• Exposure: RSV vaccination‡\n• Index date:  October 1, 2023\n• Censoring events:  \n– RSV hospitalization§\n– Other censoring event¶\n– End of study period (February 24, 2024)\n• VE = (1 - adjusted hazard ratio**) x 100%\nwhere adjusted hazard ratio = 𝑟𝑎𝑡𝑒  𝑜𝑓 𝑅𝑆𝑉  ℎ𝑜𝑠𝑝𝑖𝑡𝑎𝑙𝑖𝑧𝑎𝑡𝑖𝑜𝑛 𝑣𝑎𝑐𝑐𝑖𝑛𝑎𝑡𝑒𝑑\n𝑟𝑎𝑡𝑒  𝑜𝑓 𝑅𝑆𝑉  ℎ𝑜𝑠𝑝𝑖𝑡𝑎𝑙𝑖𝑧𝑎𝑡𝑖𝑜𝑛 𝑢𝑛𝑣𝑎𝑐𝑐𝑖𝑛𝑎𝑡𝑒𝑑\nRSV hospitalizationOther Censoring Event\nUnvaccinated person -time\nVaccinated person -time\n10/1/2023 2/24/2024\n*RSV -associated hospitalizations identified from Medicare claims data using International Classification of Diseases, Tenth Revi sion, Clinical Modification (ICD -10 CM) diagnosis code specific to RSV (J20.5, J21.0, or B97.4) listed on at \nleast one inpatient facility claim in the primary position OR a code specific to RSV pneumonia  (J12.1, ) in any position OR a code specific to RSV in any position paired with pneumonia or acute respiratory failure outcome code.\n†Defined as having at least one dialysis encounter (excluding acute kidney injury) in the 90 days preceding the index date. Pe rsons with end stage renal disease receiving dialysis are eligible for Medicare benefits, regardless of age.\n§At least 2 encounters with a discharge diagnosis for an immunocompromising condition (hematologic malignancy, solid tumor mal ignancy, transplant, rheumatologic/inflammatory disorders, other intrinsic immune conditions or \nimmunodeficiency) within 183 days before the index date.\n¶A single beneficiary can contribute follow -up time in multiple categories.\n**Adjusted for sex, age group, race, social vulnerability index (SVI), 2022 -2023 influenza vaccination status, and Updated (2023 -2024 Formula) COVID -19 vaccination status. VE was calculated as (1 − adjusted hazard ratio) x 100%.\n††Record of receipt of RSV vaccine dose versus no recorded receipt of RSV vaccine dose using administration codes listed on cla ims data.  Beneficiaries were considered “vaccinated” ≥14 days after the date of vaccine dose \nadministration.\n§§ Centers for Medicare & Medicaid Services (CMS) cell suppression policy limits the minimum cell size.\n¶¶Some estimates are imprecise, which might be due to a relatively small number of persons in each level of vaccination or case  status. This imprecision indicates that the actual VE could be substantially different from the point \nestimate shown, and estimates should therefore be interpreted with caution.Medicare/ESRD: VE against RSV -associated hospitalization* among adults aged ≥65 \nyears with ESRD†, by immunocompromise status§,  October 2023 –February 2024\nImmunocompromise status | \nvaccination status# of \nBeneficiaries# of \nOutcomesMedian \nFollow -up \nTime (Days) ¶Vaccine Effectiveness, \n% (95% CI)**\nWithout  Additional Immunocompromise\nUnvaccinated (Ref) 47,177 342 146 Ref\nVaccinated†† 4,603 <11§§ 91 72 (41 -87)\nWith  Additional Immunocompromise\nUnvaccinated (Ref) 15,371 161 146 Ref\nVaccinated 2,128 <11§§ 90 83 (45 -95) ¶¶\n0 50 100\nVaccine Effectiveness, % (95% CI)RSV vaccination provided protection \nagainst RSV -associated hospitalization \namong adults with ESRD on dialysisThis slide contains corrections. To see the slide as originally presented, without corrections, please see slide 49. \nSummary\nOutcome Analysis Vaccine efficacy /effectiveness,  % (95% CI)\nSymptomatic, \nRSV -associated \nlower\nrespiratory tract \ndisease (LRTD)GSK trial (≥2 or 3 sx LRTD, primary endpoint)†83 (58 –94)\nPfizer trial (≥2 sx LRTI, co -primary endpoint) * 67 (29 –86) \nPfizer trial (≥3 sx LRTI, co -primary endpoint) * 86 (32 –99)\nRSV -associated \nhospitalizationIVY Network, adults ≥60 years§75 (50 –87)\nVISION, adults ≥60 years, immunocompetent 80 (71 –85)\nVHA, adults ≥60 years§82 (69 –89) \nMedicare ESRD, otherwise immunocompetent, ≥65y 72 (41 -87)\nVISION, immunocompromised 73 (48 –85)\nMedicare ESRD, additional immunocompromise, ≥65y 83 (45 -95)Observational VE studies show RSV vaccines protect against severe RSV \ndisease, similar to results from trials, although endpoints differ\n0 20 40 60 80 100\nVaccine effectiveness, % (95% CI)\n† Papi  A, et. al. Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older Adults. N Engl J Med . 2023;388:595 –608.  See slide 43 for detailed definitions. \n* Walsh E, et. al. Efficacy and Safety of a Bivalent RSV Prefusion F Vaccine in Older Adults. N Engl J Med . 2023;388:1465 –77.  See slide 43 for detailed definitions.\n§ Includes patients with immunocompromising conditions in the displayed VE estimate.Abbreviations:  LRTI = lower respiratory tract infection; LRTD = lower respiratory tract disease; sx = symptoms or signs; y = yearsThis slide contains corrections. To see the slide as originally presented, without corrections, please see slide 51. \nLimitations of observational VE studies\n•RSV vaccine uptake in these study populations was 5 –10% \n-Early adopters of new vaccines may have different healthcare -seeking behaviors than the general population, \nwhich could bias VE estimates upward*\n•Multivariable adjustment and inverse -probability -of-vaccination -weighting were used \nto minimize bias, but residual bias from unmeasured confounding may remain\n•Definitions of immunocompromise varied across studies and studies were not powered \nto assess VE for specific types of immunosuppression\n•Median duration since RSV vaccination in these studies was 3 –4 months, which is \ninsufficient follow -up time to determine duration of RSV vaccine effectiveness beyond a \nseason\n* Sullivan SG, et. al. Am J Epidemiol.  2016;184(5):345 –353.\n•Under real -world conditions, RSV vaccination (GSK or Pfizer) provided protection \nagainst severe RSV disease among US adults aged ≥60 years in this first season of use\n•These results build on those from RSV vaccine trials in two ways:\n-Provide evidence of VE against RSV -associated ED visits, hospitalizations, and critical illness\n-Demonstrate protection in a population that more closely represents those at high -risk of \nsevere RSV disease, including\n•Adults aged 75 years or older\n•Adults with a composite of various immunocompromising conditions\n•Adults with underlying conditions, especially cardiopulmonary disease\n•Ongoing monitoring of RSV VE is needed to confirm findings from this season and \nassess durability of RSV vaccine protectionConclusions\nAcknowledgements \nCDC\nAmadea Britton\nAllison Avrich Ciesla\nFatimah S. Dawood\nJennifer DeCuir\nMonica Dickerson\nKatherine Fleming -Dutra\nShikha Garg\nDanica Gomes\nKelly Hatfield\nAmber Kautz\nRuth Link -Gelles\nJosephine Mak\nMichael Melgar\nMorgan Najdowski\nShannon Novosad\nLakshmi Panagiotakopoulos\nAmanda Payne\nCaitlin Ray\nEmily L. Reeves\nMark W. Tenforde\nMegan Wallace\nRyan Wiegand \nKatherine A. Yuengling\nCMS Collaborators\nCMS\nAlia Bayatti\nAcumen\nHeng -Ming Sung\nIvy Zhang\nCarla Gomez Victor\nYenlin  Lai\nBradley Lufkin\nYoganand ChillarigeVISION Collaborators\nColumbia University\nKarthik Natarajan\nHealthPartners\nMalini B. DeSilva\nOmobosola  O. Akinsete\nCharlene E. McEvoy\nInih J. Essien\nIntermountain Health\nKristin Dascomb\nTamara Sheffield\nDaniel Bride\nJulie Arndorfer\nKaiser Permanente \nCenter for Health Research\nStephanie A. Irving\nAllison L. Naleway\nPadma Koppolu\nKaiser Permanente \nNorthern California\nNicola P. Klein\nBruce Fireman\nOusseny  Zerbo\nJulius Timbol\nKristin Goddard\nRegenstrief\nShaun J. Grannis\nBrian E. Dixon\nWilliam F. Fadel\nColin Rogerson\nKatie AllenVA Collaborators\nGrant Huang\nMihaela  Aslan\nKristina L. Bajema\nGeorge N. Ioannou\nLei Yan\nYuli Li\nStephanie Argraves\nNallakkandi  Rajeevan\nAlexandra Fox\nRobert Vergun\nKristin Berry\nDavid Bui\nYuan Huang\nHung -Mo Lin\nDenise Hynes\nCynthia Lucero -Obusan\nPatricia Schirmer\nFrancesca Cunningham\nRene LaFleur\nWilliam Lance\nAlysia Maffucci\nFDA\nBARDAIVY Collaborators\nVanderbilt University \nWesley H. Self\nCarlos G. Grijalva\nYuwei Zhu\nCassandra A. Johnson\nH. Keipp Talbot\nKelsey N. Womack\nJillian P. Rhoads\nAdrienne Baughman\nSydney A. Swan\nTodd W. Rice\nJonathan D. Casey\nPaul W. Blair\nNatasha Halasa\nJames D. Chappell\nBaylor, Scott and White\nManju Gaglani\nShekhar Ghamande\nTresa McNeal\nCristie Columbus\nRobert L. Gottlieb\nCatherine Raver\nBaystate Medical Center\nJay S. Steingrub\nBeth Israel Medical Center\nNathan I. Shapiro\nCleveland Clinic\nAbhijit Duggal\nEmory University\nLaurence W. Busse\nWilliam S. Bender\nHennepin County \nMatthew E. Prekker\nAnne Frosch\nJohns Hopkins University\nDavid N. HagerIVY Collaborators\nIntermountain Health\nIthan D. Peltan\nSamuel M. Brown\nEmory University\nLaurence W. Busse\nWilliam S. Bender\nHennepin County \nMatthew E. Prekker\nAnne Frosch\nIntermountain Health\nIthan D. Peltan\nSamuel M. Brown\nMontefiore Medical Center\nMichelle N. Gong\nAmira Mohamed\nOhio State Medical Center\nMatthew C. Exline\nOregon Health and Sciences \nUniversity\nCatherine L. Hough\nAkram Khan\nStanford University\nJennifer G. Wilson\nUniversity of Arizona\nJarrod Mosier\nBeth Salvagio  Campbell\nUCLA\nNida Qadir\nSteven Y. Chang\nUniversity of Colorado\nAdit A. Ginde\nUniversity of Iowa\nNicholas M. Mohr\nAnne Zepeski\nUniversity of Miami\nChristopher MallowIVY Collaborators\nUniversity of Michigan\nAdam S. Lauring\nEmily T. Martin\nAleda M. Leis\nUniversity of Utah\nEstelle S. Harris\nUniversity of Washington\nNicholas J. Johnson\nVasisht  Srinivasan\nWake Forest University\nKevin W. Gibbs\nWashington University\nJennie H. Kwon\nBijal Parikh\nHenry Ford Health\nIvana A. Vaughn\nMayur Ramesh\nYale University\nBasmah SafdarVISION Collaborators\nUniversity of Colorado\nToan C. Ong\nSuchitra Rao\nDavid Mayer\nMichelle Barron\nWestat\nSarah Ball\nMargaret Dunne\nPatrick Mitchell\nSarah E. Reese\nElizabeth A.K. Rowley\nJanet Watts\nZack Weber\nAdditional slides\nCumulative RSV vaccine coverage among adults aged \n≥60 years, September 30, 2023 – May 11, 2024 \nData source: National Immunization Survey – Adult COVID Module. Available at: Respiratory Syncytial Virus (RSV) Vaccination Coverage and Intent for Vaccination, Adults 60 Years and Older, United \nStates | CDC . Accessed on June 13, 2024.By May 11, 2024, an estimated \n24% of adults aged ≥60 years \nhad received RSV vaccination\nMost RSV vaccinations were administered in pharmacy \nsettings\nData source: Dr. Carla Black. Implementation update: older adult RSV vaccination. ACIP Meeting, February 29, 2024. Available at: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2024 -02-28-\n29/04 -RSV-Adults -Black -508.pdf   By May 11, 2024, an estimated \n24% of adults aged ≥60 years \nhad received RSV vaccination\n\nTest-negative Design (TND)\n•Advantage of TND compared with traditional \ncase -control or cohort analyses\n-Efficiency in enrolling cases and controls from the \nsame location with the same clinical syndrome\n-Reduces selection bias due to healthcare -seeking \nbehaviorStandardized clinical syndrome \nis used to enroll symptomatic \npatients seeking medical care\nLaboratory test\nPositive\nCaseNegative\nControl\nChua H, et. al., The Use of Test -negative Controls to Monitor Vaccine Effectiveness: A Systematic Review of Methodology. Epidemiology . 2020;31(1): 43 –64.\nDefinitions of immunocompromise for each observational \nVE analysis\nAnalysis Immunocompromising conditions\nIVY Network Active solid tumor or hematologic malignancy (i.e., newly diagnosed malignancy or treatment for a \nmalignancy within the previous 6 months), solid organ transplant; bone marrow/hematopoietic stem \ncell transplant, HIV infection, congenital immunodeficiency syndrome; use of an immunosuppressive \nmedication within the previous 30 days.\nVISION Defined based on presence of ICD -10 code corresponding to hematologic malignancy, solid \nmalignancy, transplant, rheumatologic/inflammatory disorders, other intrinsic immune condition or \nimmunodeficiency, or HIV in discharge diagnoses.\nVeterans Health Administration Receipt of immunosuppressive or cancer medications within 90 days or 1 year of index date, \ndepending on the medication OR\nHIV with most recent CD4 lymphocyte count ≤2 years prior to index date ≤200 cells/mm3 OR\nHematologic malignancy documented ≤2 years prior to index date.\nMedicare/ESRD At least 2 encounters with a discharge diagnosis for an immunocompromising condition (Hematologic \nmalignancy, other intrinsic immune conditions or immunodeficiency, solid malignancy, transplant, or \nrheumatologic/inflammatory disorders) within 183 days before the index date.\nDefinitions of chronic lung disease for each observational \nVE analysis\nAnalysis Chronic lung disease definition\nIVY Network Asthma, chronic obstructive pulmonary disease, cystic fibrosis, pulmonary fibrosis, pulmonary \nhypertension, home oxygen use (except at night for sleep disorder), tracheostomy, home non -invasive \nventilation (except at night for sleep disorder), home invasive ventilation.\nVISION Documentation of ICD -10 code corresponding to one or more of the following conditions among \ndischarge diagnosis codes for encounter:  asthma, chronic obstructive pulmonary disease, cystic \nfibrosis, other chronic lung disease.\nVeterans Health Administration Any documentation of the following ICD -10 codes within 2 years prior to the index date: B44.81, I27.x, \nI28.x, J40.x, J41.x, J42.x, J43.x, J44.0, J44.1, J44.9, J45.x, J47.x, J63.1, J68.4, J70.1, J81.1, J82.8x, J84.03, \nJ84.10, J84.112, J84.17x, J84.89, J98.2 -.3, M05.10x -.19, M30.1, P25.0, P25.8, Q32.2 -.2, Q33.x, T79.7XXx, \nT81.82Xx \nMedicare/ESRD Claim listing ICD -10 code corresponding to one or more of the following conditions within 365 days \nfrom the index date:  asthma, chronic obstructive pulmonary disease, other chronic lung disease.\nDefinitions of cardiovascular disease for each \nobservational VE analysis\nAnalysis Cardiovascular disease definition\nIVY Network Heart failure, peripheral vascular disease that limits mobility, prior myocardial infarction, cardiac \narrhythmias (including atrial fibrillation, and ventricular arrhythmias), valvular heart disease, \nhypertension, untreated thoracic or abdominal aneurysm.\nVISION Documentation of ICD -10 code corresponding to one or more of the following conditions among \ndischarge diagnosis codes for encounter: heart failure, ischemic heart disease, hypertension, other \nheart disease, pulmonary embolism, heart valve disorders, atrial fibrillation and flutter, congenital heart \ndisease.\nVeterans Health Administration Any documentation of the following ICD -10 codes within 2 years prior to the index date: ICD10 codes: \nE08.52, E09.52, E10.5x, E11.5x, E13.5x, G45.9, I20.0 -.1, I20.8 -.9, I20.0x, I21.0x -.9x, I21.Ax, I22.x, I24.x, I25.x, \nI50.x, I63.x, I65.x, I70.x, I73.9, I74.0x, I74.10, I74.19, I74.3 -.8, I75.02x, I77.1, I96.x, L97.101 -.104, L97.109, \nL97.111 -.114, L97.119, L97.121 -.124, L97.129, L97.201 -.204, L97.209, L97.211 -.214, L97.219, L97.221 -.224, \nL97.229, L97.301 -.304, L97.309, L97.311 -.314, L97.319, L97.321 -.324, L97.329, L97.401 -.404, L97.409, \nL97.411 -.414, L97.419, L97.421 -.424, L97.429, L97.501 -.504, L97.509, L97.511 -.514, L97.519, L97.521 -.524, \nL97.529, L97.801 -.804, L97.809, L97.811 -.814, L97.819, L97.821 -.824, L97.829, L97.901 -.904, L97.909, \nL97.911 -.914, L97.919, L97.921 -.924, L97.929, Z95.1, Z95.5, Z98.61\nMedicare/ESRD Claim listing ICD -10 code corresponding to one or more of the following conditions within 365 days \nfrom the index date:  heart failure, ischemic heart disease, hypertension, other cardiovascular disease.\nCase definitions of lower respiratory tract illness or \ndisease in RSV vaccine trials1,2 \n1Papi A, et al; AReSVi -006 Study Group. Respiratory syncytial virus prefusion F protein vaccine in older adults. N Engl J Med . 2023;388(7):595 -608\n2Walsh EE, et al; RENOIR Clinical Trial Group. Efficacy and safety of a bivalent RSV prefusion F vaccine in older adults. N Engl J Med . 2023;388(16):1465 -1477Pfizer ( Abrysvo )2\n▪ RSV LRTI with ≥2 lower respiratory \nsigns/symptoms (co -primary outcome)\n▪ RSV LRTI with ≥3 lower respiratory \nsigns/symptoms (co -primary outcome)\n▪ Lower respiratory signs/symptoms :\n•Sputum, cough, shortness of \nbreath, wheezing, tachypneaGSK ( Arexvy )1\n▪ RSV LRTD (primary outcome)\n– ≥2 lower respiratory symptoms  or signs , \nincluding ≥1 sign, OR\n– ≥3 lower respiratory symptoms\n▪ Lower respiratory symptoms :\n– Sputum, cough, dyspnea\n▪ Lower respiratory signs :\n– Wheezing, crackles/rhonchi, tachypnea, \nhypoxemia, oxygen  supplementation\nOriginal slides \n•The following slides contain errata. They are being shared here for a \nrecord of what was presented at the June 26, 2024, ACIP meeting. \n•Corrected slides are available in the main presentation. \n•Corrected slides with changes highlighted are included in the \nfollowing slides.\n44\nComparison of demographic characteristics among \nIVY , VISION, VHA, and Medicare/ESRD studies\nIVY ,\nno. (col %)VISION ,\nno. (col %)VHA ,\nno. (col %)Medicare/ESRD ,\nno. (col %)\nCharacteristic Total no.\nof\npatientsTotal no.\nof\npatientsTotal no.\nof\npatientsTotal no.\nof\npatients\nAll patients 2,978 36,706 293,704§69,279\nMedian age, years (IQR) 72 (66 –80) 76 (69 –84) 76 (72 –80) 74 (70-80)\nAge group, years\n 60–74 1756 (59) 16,055 (44) 125,124 (43) 34,614 (50)‡\n ≥75 1222 (41) 20,651 (56) 168,580 (57) 34,665 (50)\nRace and ethnicity\n White, non -Hispanic 1867 (63) 27,057 (74) 225,713 (77) 42,157 (61)\n Black, non -Hispanic 582 (20) 3,160 (9) 30,359 (10) 14,767 (21)\n Hispanic or Latino, any race 335 (11) 2,789 (8) 11,302 (4) 3,983 (6)\n Other race, non -Hispanic*101 (3) 3,395 (9) 5,971 (2) 3,604 (5)\n Unknown†93 (3) 305 (1) 20,358 (7) -\n* For VISION, “Other race, non -Hispanic” includes persons reporting non -Hispanic ethnicity and any of the following for race: Am erican Indian or Alaska Native, Asian, Native Hawaiian or other Pacific Islander, \nother races not listed, and multiple races; because of small numbers, these categories were combined. For IVY, “Other race, n on-Hispanic” includes Asian, American Indian or Alaska Native, and Native Hawaiian \nor other Pacific Islander; because of small numbers, these categories were combined.\n† For VISION, “Unknown” includes persons with missing race and ethnicity in their electronic health records. For IVY, “Unknow n” includes patients who self -reported their race and ethnicity as “Other” and those \nfor whom race and ethnicity were unknown. For VHA “Unknown” includes missing, unknown, or declined race or ethnicity.\n§146,852 vaccinated persons were matched to 582,936 unvaccinated participants who were equally weighted to correspond to 146,8 52 matched unvaccinated participants. \n‡Evaluation of Medicare fee -for-service claims data was restricted to adults aged 65 years and older.This slide was presented at ACIP on June 26, 2024, and contains errata (highlighted). To see the corrected slide, see slide 5 ; to see the corrected slide with changes highlighted, see slide 46. \nComparison of demographic characteristics among \nIVY , VISION, VHA, and Medicare/ESRD studies\nIVY , \nno. (col %)VISION , \nno. (col %)VHA , \nno. (col %)Medicare/ESRD , \nno. (col %)\nCharacteristic Total no. \nof\npatientsTotal no. \nof\npatientsTotal no. \nof\npatientsTotal no. \nof\npatients\nAll patients 2,978 36,706 293,704§69,279\nMedian age, years (IQR) 72 (66 –80) 76 (69 –84) 76 (72 –80) 75 (70-80)\nAge group, years\n60–74 1756 (59) 16,055 (44) 125,124 (43) 34,614 (50)‡\n≥75 1222 (41) 20,651 (56) 168,580 (57) 34,665 (50)\nRace and ethnicity\nWhite, non -Hispanic 1867 (63) 27,057 (74) 225,713 (77) 42,157 (61)\nBlack, non -Hispanic  582 (20) 3,160 (9) 30,359 (10) 14,767 (21)\nHispanic or Latino, any race 335 (11) 2,789 (8) 11,302 (4) 3,983 (6)\nOther race, non -Hispanic*101 (3) 3,395 (9) 5,971 (2) 8,372 (12)\nUnknown†93 (3) 305 (1) 20,358 (7) -\n* For VISION, “Other race, non -Hispanic” includes persons reporting non -Hispanic ethnicity and any of the following for race: Am erican Indian or Alaska Native, Asian, Native Hawaiian or other Pacific Islander, \nother races not listed, and multiple races; because of small numbers, these categories were combined. For IVY, “Other race, n on-Hispanic” includes Asian, American Indian or Alaska Native, and Native Hawaiian \nor other Pacific Islander; because of small numbers, these categories were combined. For Medicare/ESRD, \"Other race, non -Hispanic\" includes Asian/Pacific Islander, non -Hispanic, Other, non -Hispanic, and \nUnknown.\n† For VISION, “Unknown” includes persons with missing race and ethnicity in their electronic health records. For IVY, “Unknow n” includes patients who self -reported their race and ethnicity as “Other” and those \nfor whom race and ethnicity were unknown. For VHA “Unknown” includes missing, unknown, or declined race or ethnicity.\n§146,852 vaccinated persons were matched to 582,936 unvaccinated participants who were equally weighted to correspond to 146,8 52 matched unvaccinated participants. \n‡Evaluation of Medicare fee -for-service claims data was restricted to adults aged 65 years and older.This slide has been corrected (highlighted). To see the slide as originally presented, please see slide 45; to see a correcte d, unhighlighted version, see slide 5. \nComparison of clinical characteristics among IVY , \nVISION, VHA, and Medicare/ESRD studies\nIVY ,\nno. (col %)VISION ,\nno. (col %)VHA ,\nno. (col %)Medicare/ESRD ,\nno. (col %)\nCharacteristic Total no.\nof\npatientsTotal no.\nof\npatientsTotal no.\nof\npatientsTotal no.\nof\npatients\nAll patients 2,978 36,706 293,704 69,279\nNo. of chronic medical condition categories\n0 71 (2) 2,111 (6) 17,554 (6) 0 (0)\n1 416 (14) 3,845 (10) 58,757 (20) 312 <1)\n2 783 (26) 15,420 (42) 83,992 (29) 1,497 (2)\n3 863 (29) 15,330 (42) 73,296 (25) 9,242 (13)\n≥4 845 (28) 2,111 (6) 60,106 (21) 58,228 (84)\nImmunocompromised*720 (24) 8,435 (23) 32,996 (11) 17,499 (25)\nChronic lung disease†1423 (48) 17,541 (48) 88,648 (30) 38,529 (56)\nCardiovascular disease§2501 (84) 28,822 (79) 122,015 (42) 66,987 (97)\nRSV vaccinated 265 (9) 3,275 (9) 146,852 (50)¶6,73 4 (10)\n Received GSK (Arexvy) 137 (61)** 2,409 (74) 43,875 (30) 4,562 68)\n Received Pfizer (Abrysvo) 89 (39) ** 865 (36) 101,623 (69) 2,172 (32)\n* Slide 41 provides definitions of immunocompromise from each network\n† Slide 42 provides definitions of chronic lung disease from each network\n§ Slide 43 provides definitions of cardiovascular disease from each network\n¶ Each RSV -vaccinated patient was matched to up to 4 unvaccinated, equally weighted patients, resulting in 50% of matched persons having an RSV vaccination. Among match -eligible patients, 4.5% received RSV vaccination.\n** Of 265 RSV vaccinated patients in IVY, 226 (85%) had known product type, which is used as the denominator for these percentag es.This slide was presented at ACIP on June 26, 2024, and contains errata (highlighted). To see the corrected slide, see slide 6 ; to see the corrected slide with changes highlighted, see slide 48. \nComparison of clinical characteristics among IVY , \nVISION, VHA, and Medicare/ESRD studies\nIVY , \nno. (col %)VISION , \nno. (col %)VHA , \nno. (col %)Medicare/ESRD , \nno. (col %)\nCharacteristic Total no. \nof\npatientsTotal no. \nof\npatientsTotal no. \nof\npatientsTotal no. \nof\npatients\nAll patients 2,978 36,706 293,704 69,279\nNo. of chronic medical condition categories\n0 71 (2) 2,111 (6) 17,554 (6) 0 (0)\n1 416 (14) 3,845 (10) 58,757 (20) 312 (<1)\n2 783 (26) 15,420 (42) 83,992 (29) 1,497 (2)\n3 863 (29) 15,330 (42) 73,296 (25) 9,242 (13)\n≥4 845 (28) 2,111 (6) 60,106 (21) 58,228 (84)\nImmunocompromised*720 (24) 8,435 (23) 32,996 (11) 17,499 (25)\nChronic lung disease†1423 (48) 17,541 (48) 88,648 (30) 38,529 (56)\nCardiovascular disease§2501 (84) 28,822 (79) 122,015 (42) 66,987 (97)\nRSV vaccinated 265 (9) 3,275 (9) 146,852 (50)¶6,73 1 (10)\nReceived GSK (Arexvy) 137 (61)** 2,409 (74) 43,875 (30) 4,559 (68)\nReceived Pfizer (Abrysvo) 89 (39) ** 865 (36) 101,623 (69) 2,172 (32)\n* Slide 41 provides definitions of immunocompromise from each network\n† Slide 42 provides definitions of chronic lung disease from each network\n§ Slide 43 provides definitions of cardiovascular disease from each network\n¶ Each RSV -vaccinated patient was matched to up to 4 unvaccinated, equally weighted patients, resulting in 50% of matched persons having an RSV vaccination. Among match -eligible patients, 4.5% received RSV vaccination.\n** Of 265 RSV vaccinated patients in IVY, 226 (85%) had known product type, which is used as the denominator for these percentag es.This slide has been corrected (highlighted). To see the slide as originally presented, please see slide 47; to see a correcte d, unhighlighted version, see slide 6. \n*RSV -associated hospitalizations identified from Medicare claims data using International Classification of Diseases, Tenth Revi sion, Clinical Modification (ICD -10 CM) diagnosis code specific to RSV (J20.5, J21.0, or B97.4) listed on at \nleast one inpatient facility claim in the primary position OR a code specific to RSV pneumonia  (J12.1, ) in any position OR a code specific to RSV in any position paired with pneumonia or acute respiratory failure outcome code.\n†Defined as having at least one dialysis encounter (excluding acute kidney injury) in the 90 days preceding the index date. Pe rsons with end stage renal disease receiving dialysis are eligible for Medicare benefits, regardless of age.\n§At least 2 encounters with a discharge diagnosis for an immunocompromising condition (hematologic malignancy, solid tumor mal ignancy, transplant, rheumatologic/inflammatory disorders, other intrinsic immune conditions or \nimmunodeficiency) within 183 days before the index date.\n¶A single beneficiary can contribute follow -up time in multiple categories.\n**Adjusted for sex, age group, race, social vulnerability index (SVI), 2022 -2023 influenza vaccination status, and Updated (2023 -2024 Formula) COVID -19 vaccination status. VE was calculated as (1 − adjusted hazard ratio) x 100%.\n††Record of receipt of RSV vaccine dose versus no recorded receipt of RSV vaccine dose using administration codes listed on cla ims data.  Beneficiaries were considered “vaccinated” ≥14 days after the date of vaccine dose \nadministration.\n§§ Centers for Medicare & Medicaid Services (CMS) cell suppression policy limits the minimum cell size.\n¶¶Some estimates are imprecise, which might be due to a relatively small number of persons in each level of vaccination or case  status. This imprecision indicates that the actual VE could be substantially different from the point \nestimate shown, and estimates should therefore be interpreted with caution.Medicare/ESRD: VE against RSV -associated hospitalization* among adults aged ≥65 \nyears with ESRD†, by immunocompromise status§,  October 2023 –February 2024\nImmunocompromise status | \nvaccination status# of \nBeneficiaries# of \nOutcomesMedian \nFollow -up \nTime (Days) ¶Vaccine Effectiveness, \n% (95% CI)**\nWithout  Additional Immunocompromise\nUnvaccinated (Ref) 47,17 6 275 146 Ref\nVaccinated†† 4,60 4 <11§§ 91 78 (45–91)\nWith  Additional Immunocompromise\nUnvaccinated (Ref) 15,3 69 136 146 Ref\nVaccinated 2,130 <11§§ 90 80 (31–94) ¶¶\n0 50 100\nVaccine Effectiveness, % (95% CI)RSV vaccination provided protection \nagainst RSV -associated hospitalization \namong adults with ESRD on dialysisThis slide was presented at ACIP on June 26, 2024, and contains errata (highlighted). To see the corrected slide, see slide 3 0; to see the corrected slide with changes highlighted, see slide 50. \n*RSV -associated hospitalizations identified from Medicare claims data using International Classification of Diseases, Tenth Revi sion, Clinical Modification (ICD -10 CM) diagnosis code specific to RSV (J20.5, J21.0, or B97.4) listed on at \nleast one inpatient facility claim in the primary position OR a code specific to RSV pneumonia  (J12.1, ) in any position OR a code specific to RSV in any position paired with pneumonia or acute respiratory failure outcome code.\n†Defined as having at least one dialysis encounter (excluding acute kidney injury) in the 90 days preceding the index date. Pe rsons with end stage renal disease receiving dialysis are eligible for Medicare benefits, regardless of age.\n§At least 2 encounters with a discharge diagnosis for an immunocompromising condition (hematologic malignancy, solid tumor mal ignancy, transplant, rheumatologic/inflammatory disorders, other intrinsic immune conditions or \nimmunodeficiency) within 183 days before the index date.\n¶A single beneficiary can contribute follow -up time in multiple categories.\n**Adjusted for sex, age group, race, social vulnerability index (SVI), 2022 -2023 influenza vaccination status, and Updated (2023 -2024 Formula) COVID -19 vaccination status. VE was calculated as (1 − adjusted hazard ratio) x 100%.\n††Record of receipt of RSV vaccine dose versus no recorded receipt of RSV vaccine dose using administration codes listed on cla ims data.  Beneficiaries were considered “vaccinated” ≥14 days after the date of vaccine dose \nadministration.\n§§ Centers for Medicare & Medicaid Services (CMS) cell suppression policy limits the minimum cell size.\n¶¶Some estimates are imprecise, which might be due to a relatively small number of persons in each level of vaccination or case  status. This imprecision indicates that the actual VE could be substantially different from the point \nestimate shown, and estimates should therefore be interpreted with caution.Medicare/ESRD: VE against RSV -associated hospitalization* among adults aged ≥65 \nyears with ESRD†, by immunocompromise status§,  October 2023 –February 2024\nImmunocompromise status | \nvaccination status# of \nBeneficiaries# of \nOutcomesMedian \nFollow -up \nTime (Days) ¶Vaccine Effectiveness, \n% (95% CI)**\nWithout  Additional Immunocompromise\nUnvaccinated (Ref) 47,17 7 342 146 Ref\nVaccinated†† 4,60 3 <11§§ 91 72 (41-87)\nWith  Additional Immunocompromise\nUnvaccinated (Ref) 15,3 71 161 146 Ref\nVaccinated 2,128 <11§§ 90 83 (45-95) ¶¶\n0 50 100\nVaccine Effectiveness, % (95% CI)RSV vaccination provided protection \nagainst RSV -associated hospitalization \namong adults with ESRD on dialysisThis slide has been corrected (highlighted). To see the slide as originally presented, please see slide 49; to see a correcte d, unhighlighted version, see slide 30. \nOutcome Analysis Vaccine efficacy /effectiveness,  % (95% CI)\nSymptomatic, \nRSV -associated \nlower\nrespiratory tract \ndisease (LRTD)GSK trial (≥2 or 3 sx LRTD, primary endpoint)†83 (58 –94)\nPfizer trial (≥2 sx LRTI, co -primary endpoint) * 67 (29 –86) \nPfizer trial (≥3 sx LRTI, co -primary endpoint) * 86 (32 –99)\nRSV -associated \nhospitalizationIVY Network, adults ≥60 years§75 (50 –87)\nVISION, adults ≥60 years, immunocompetent 80 (71 –85)\nVHA, adults ≥60 years§82 (69 –89) \nMedicare ESRD, otherwise immunocompetent, ≥65y 78 (45–91)\nVISION, immunocompromised 73 (48 –85)\nMedicare ESRD, additional immunocompromise, ≥65y 80 (31–94)Observational VE studies show RSV vaccines protect against severe RSV \ndisease, similar to results from trials, although endpoints differ\n0 20 40 60 80 100\nVaccine effectiveness, % (95% CI)\n† Papi  A, et. al. Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older Adults. N Engl J Med . 2023;388:595 –608.  See slide 4 3 for detailed definitions. \n* Walsh E, et. al. Efficacy and Safety of a Bivalent RSV Prefusion F Vaccine in Older Adults. N Engl J Med . 2023;388:1465 –77.  See slide 4 3 for detailed definitions.\n§ Includes patients with immunocompromising conditions in the displayed VE estimate.Abbreviations:  LRTI = lower respiratory tract infection; LRTD = lower respiratory tract disease; sx = symptoms or signs; y = yearsThis slide was presented at ACIP on June 26, 2024, and contains errata (highlighted). To see the corrected slide, see slide 3 2; to see the corrected slide with changes highlighted, see slide 52. \nOutcome Analysis Vaccine efficacy /effectiveness,  % (95% CI)\nSymptomatic, \nRSV -associated \nlower\nrespiratory tract \ndisease (LRTD)GSK trial (≥2 or 3 sx LRTD, primary endpoint)†83 (58 –94)\nPfizer trial (≥2 sx LRTI, co -primary endpoint) * 67 (29 –86) \nPfizer trial (≥3 sx LRTI, co -primary endpoint) * 86 (32 –99)\nRSV -associated \nhospitalizationIVY Network, adults ≥60 years§75 (50 –87)\nVISION, adults ≥60 years, immunocompetent 80 (71 –85)\nVHA, adults ≥60 years§82 (69 –89) \nMedicare ESRD, otherwise immunocompetent, ≥65y 72 (41-87)\nVISION, immunocompromised 73 (48 –85)\nMedicare ESRD, additional immunocompromise, ≥65y 83 (45-95)Observational VE studies show RSV vaccines protect against severe RSV \ndisease, similar to results from trials, although endpoints differ\n0 20 40 60 80 100\nVaccine effectiveness, % (95% CI)\n† Papi  A, et. al. Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older Adults. N Engl J Med . 2023;388:595 –608.  See slide 4 3 for detailed definitions. \n* Walsh E, et. al. Efficacy and Safety of a Bivalent RSV Prefusion F Vaccine in Older Adults. N Engl J Med . 2023;388:1465 –77.  See slide 4 3 for detailed definitions.\n§ Includes patients with immunocompromising conditions in the displayed VE estimate.Abbreviations:  LRTI = lower respiratory tract infection; LRTD = lower respiratory tract disease; sx = symptoms or signs; y = yearsThis slide has been corrected (highlighted). To see the slide as originally presented, please see slide 51; to see a correcte d, unhighlighted version, see slide 32.", "summary": "Effectiveness of adult respiratory syncytial virus (RSV)   vaccines, 2023 –2024 Diya Surie, MD Coronavirus and Other Respiratory Viruses Division Centers for Disease Control and Prevention June 26, 2024National Center for Immunization and Respiratory Diseases This presentation has been  corrected. See slides 5, 6, 30,  and 32 for corrected slides. The  original slides are included at  the end of the presentation. •Purpose of randomized vaccine trials is to answer the question:Goal of…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/07-RSV-Adult-Surie-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 52}
{"title": "08 RSV Adult Hutton 508", "content": "Economic Analysis of RSV Vaccination \nin Adults 50 years and Older\nDavid W. Hutton, PhD, MS\nAssociate Professor, Health Management and Policy, School of Public Health\nAssociate Professor of Global Public Health, School of Public Health\nAssociate Professor, Industrial and Operations Engineering, College of Engineering\nUniversity of Michigan\n1\nResearch Team\nUniversity of Michigan\n•David Hutton, PhD\n•Lisa Prosser, PhD\n•Angela Rose, MPH\n•Christina Nyamuswa , MSCDC\n•Michael Melgar, MD\n•Amadea Britton, MD \n•Lauren Roper, MPH\n•Mila Prill, MSPH\n•Jamison Pike, PhD\n•Ismael Ortega -Sanchez, PhD\n•Andrew Leidner, PhD\n•Fiona Havers, MD\n•Michael Whitaker, MPH\n•Rebecca Woodruff, PhD\n•Huong Pham, MPH\n•Bryan Stierman , MD\n2\nConflicts of interest  statements\n•No known conflict of interests.\n3\nUpdates from last presentation before ACIP in \nJune 2023*\n•Risk-Based Analysis\n•Groups based on chronic medical conditions (CMCs) and age\n•Added Moderna Vaccine\n•Other New Inputs\n•RSV Epidemiology\n•Hospitalization incidence by chronic medical conditions\n•Outpatient incidence by chronic medical condition\n•RSV-mortality inclusive of deaths in and out of hospital\n•Real -world observational vaccine effectiveness of RSV protein subunit vaccination \n(Pfizer/GSK)\n•Duration of protection derived from clinical trial efficacy waning over time using all available \nfollow up time\n•Vaccine adverse events after protein subunit RSV vaccination\n•Real world evidence on local and systemic vaccine reactions (V -safe)\n•Risk of Guillain -Barre syndrome (GBS) observed after RSV vaccination in administrative claims \ndata through FDA/CMS partnership\n4* DW Hutton, “Economic Analysis of RSV Vaccination in Older Adults” June 21, 2023 (cdc.gov)\nMethods \n5\nMethods: Study question\n•Determine the cost -effectiveness of RSV vaccination by:\n•Comparing vaccination to no vaccination using the incremental cost -\neffectiveness ratio\n•Scenario analyses.\n•Perspective: Societal\n6\nMethods: Intervention(s)\n•Target population: US adults aged ≥50 years, stratified by age, chronic \nmedical conditions\n•Adults aged ≥75 years\n•Adults aged 60 -74 years with at least one chronic medical condition*\n•Adults aged 50 -59 years with at least one chronic medical condition*\n•Interventions: RSV vaccination \n•Protein subunit RSV vaccination (Pfizer’s ABRYSVO, GSK’s AREXVY)\n•Moderna RSV vaccination (Moderna’s mRESVIA )\n•Each compared to no vaccination\n7*At least one of: chronic obstructive pulmonary disease (COPD), asthma, coronary artery disease, chronic kidney disease, \ndiabetes mellitus, severe obesity (BMI ≥40)\nCombining Pfizer and GSK in base case \n•ACIP has previously seen that product -specific cost effectiveness for \nthe two currently licensed protein subunit RSV vaccines is similar\n•Policy question does not distinguish between the two products\n•Combining products allows simplification of results and enables us to \nfocus on the policy questions \n•Product -specific results will still be shown in scenario analyses \n•Benefit/risk analyses evaluating GBS risk will be shown at the end and \ncontinue to be product -specific, understanding whether there is \nmeaningful difference between products in terms of benefit/risk \nbalance\n8\nMethods: Decision Tree Model\n9No \nVaccination\nVaccinationInfection Hospitalization\nED\nNone of the aboveOutpatientAlive\nDead\nRSV Infection\nAdverse \nEventsSystemic Reaction\nInjection Site Reaction\nNone of the aboveSerious Adverse EventInfection RSV Infection\nGuillain Barre Syndrome\nAnnual RSV Incidence\n•Hospitalization s\n•RSV-NET estimated annual hospitalizations per 100,000 population  (adjusted for under -\ndetection, including a 1.5x multiplier to account for RSV test sensitivity)\n•Source, age stratification only: Havers et al. manuscript draft, 2016 -2020\n•Source, stratification by age AND presence/absence of chronic medical conditions: Update to Woodruff \net al. analysis presented to ACIP in February 2024, 2017 -20181\n•Emergency Department visits:\n•From McLaughlin et al. meta -analysis2 (main results incorporating a 1.5x multiplier to account \nfor RSV laboratory test sensitivity).   \n•No differences by presence or absence of chronic medical conditions*\n•Outpatient:\n•The base values ( all-comers ) are from the McLaughlin et al. meta -analysis.2 \n•Values for adults with chronic cardiopulmonary conditions (e.g., COPD) are drawn from \nBelongia  et al.3 and multiplied by 1.5x for test sensitivity to align with RSV -NET and \nMcLaughlin et al. methods. \n•Non -cardiopulmonary conditions (e.g., diabetes) utilize the base values (same as for all -\ncomers)\n*Values were assumed to be the same for adults with and without chronic medical conditions. This is a conservative assumption mad e in the absence of reliable risk -stratified data on the \nincidence of emergency department visits.\n1. https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2024 -02-28-29/03 -RSV-Adults -Woodruff -508.pdf  \n2. Pfizer -sponsored: McLaughlin JM, et al. Rates of Medically Attended RSV Among US Adults: A Systematic Review and Meta -analysis. Open Forum Infect Dis. 2022 J un 17;9(7):ofac300. doi: \n10.1093/ ofid/ofac300. PMID: 35873302; PMCID: PMC9301578.\n3. Novavax sponsored: Belongia  EA, et al. Clinical features, severity, and incidence of RSV illness during 12 consecutive seasons in a community cohort of a dults ≥60 years old. In Open forum infectious \ndiseases 2018 Dec (Vol. 5, No. 12, p. ofy316). US: Oxford University Press10\nAnnual RSV incidence\n•At least one chronic medical condition (source RSV -NET):\n•Chronic obstructive pulmonary disease (COPD), OR\n•Asthma, OR\n•Coronary artery disease (CAD), OR\n•Diabetes mellitus, OR\n•Chronic kidney disease (CKD), OR\n•Severe obesity (body mass index [BMI] ≥40 kg/m2)\n•Additional chronic medical conditions evaluated in scenario analyses:\n•Heart failure1\n•Immune compromised\n•Lung transplant2\n•Hematopoietic cell transplant, allogeneic3,4\n•Hematopoietic cell transplant, autologous3,4\n1. Kujawski  SA, et al. Rates of respiratory syncytial virus (RSV) -associated hospitalization among adults with congestive heart failure -United States, 2015 -2017. PLoS  One. 2022 \nMar 9;17(3):e0264890. doi: 10.1371/journal.pone.0264890\n2. Testaert  H, et al. Incidence, management and outcome of respiratory syncytial virus infection in adult lung transplant recipients: a 9 -year retrospective multicentre  study. Clin \nMicrobiol  Infect. 2021 Jun;27(6):897 -903. doi: 10.1016/j.cmi.2020.07.050.\n3. Martino R, et al. Prospective study of the incidence, clinical features, and outcome of symptomatic upper and lower respirato ry tract infections by respiratory viruses in adult \nrecipients of hematopoietic stem cell transplants for hematologic malignancies. Biol Blood Marrow Transplant. 2005 Oct;11(10) :781-96. doi: 10.1016/j.bbmt.2005.07.007\n4. Waghmare A, et al. Supplemental Oxygen -Free Days in Hematopoietic Cell Transplant Recipients With Respiratory Syncytial Virus. J  Infect Dis. 2017 Dec 5;216(10):1235 -1244. \ndoi: 10.1093/ infdis /jix390These conditions  are considered separately \nbecause RSV epidemiologic parameters were \nderived from different published sources and \ncannot be combined with RSV -NET hospitalization \nrate estimates under “at least one” condition.\n11\nAnnual RSV incidence\n•At least one chronic medical condition (source RSV -NET):\n•Chronic obstructive pulmonary disease (COPD), OR\n•Asthma, OR\n•Coronary artery disease (CAD), OR\n•Diabetes mellitus, OR\n•Chronic kidney disease (CKD), OR\n•Severe obesity (body mass index [BMI] ≥40 kg/m2)\n•Additional chronic medical conditions evaluated in scenario analyses:\n•Heart failure1\n•Immune compromised\n•Lung transplant2\n•Hematopoietic cell transplant, allogeneic3,4\n•Hematopoietic cell transplant, autologous3,4\n121. Kujawski  SA, et al. Rates of respiratory syncytial virus (RSV) -associated hospitalization among adults with congestive heart failure -United States, 2015 -2017. PLoS  One. 2022 Mar \n9;17(3):e0264890. doi: 10.1371/journal.pone.0264890\n2. Testaert  H, et al. Incidence, management and outcome of respiratory syncytial virus infection in adult lung transplant recipients: a 9 -year retrospective multicentre  study. Clin \nMicrobiol  Infect. 2021 Jun;27(6):897 -903. doi: 10.1016/j.cmi.2020.07.050.\n3. Martino R, et al. Prospective study of the incidence, clinical features, and outcome of symptomatic upper and lower respirato ry tract infections by respiratory viruses in adult \nrecipients of hematopoietic stem cell transplants for hematologic malignancies. Biol Blood Marrow Transplant. 2005 Oct;11(10) :781-96. doi: 10.1016/j.bbmt.2005.07.007\n4. Waghmare A, et al. Supplemental Oxygen -Free Days in Hematopoietic Cell Transplant Recipients With Respiratory Syncytial Virus. J  Infect Dis. 2017 Dec 5;216(10):1235 -1244. \ndoi: 10.1093/ infdis /jix390Assumed that vaccine effectiveness was \nreduced by half in immune compromised \npopulations, compared with all others\nVaccine effectiveness (VE) of a single dose over time: \nprotein subunit RSV vaccine (combined Pfizer/GSK)\n13Linear decay to 0% \nby 24 months74%\n33%\n17%78%\n58%\n33%80%\n60%\n34%\n0%10%20%30%40%50%60%70%80%90%100%\n0 6 12 18 24 30 36Efficacy\nMonths since vaccination\nOutpatient ED Hospitalization\nVE against hospitalization and emergency department visits during months 0 -6 post -vaccination was assumed to be equal to results of  a meta -analysis of observational VE \nestimates from CDC and Veterans Health Administration analyses from the first RSV season of vaccine availability. Proportiona l waning was applied from clinical trial vaccine \nefficacy over time against RSV lower respiratory tract illness with ≥3 signs/symptoms (Pfizer ABRYSVO) and RSV lower respirat ory tract disease (GSK AREXVY) (data provided by \nmanufacturers). VE against outpatient illness was assumed to be the mean across the two products of trial efficacy against RS V acute respiratory illness.\n0%10%20%30%40%50%60%70%80%90%100%\n0 6 12 18 24 30 36Efficacy\nMonths since vaccination\nOutpatient ED HospitalizationVaccine effectiveness (VE) of a single dose over time: \nModerna RSV vaccine ( mRESVIA )\n1475%\n54%\nLinear decay to 0% \nby 24 months54%\nVE against hospitalization during months 0 -9 post -vaccination was assumed to be equal to clinical trial vaccine efficacy against  medically attended RSV lower respiratory tract \ndisease with ≥3 signs/symptoms. VE against emergency department visits and outpatient illness during months 0 -9 was assumed to b e equal to clinical vaccine efficacy against \nmedically attended RSV acute respiratory illness. VE was assumed to decline to zero by month 24 post -vaccination.\n•Pfizer and GSK systemic and injection site adverse event rates updated based on real -world V -\nsafe data:\n•Pfizer: 6% experienced severe  injection site reaction or systemic reaction\n•GSK: 10% experienced severe  injection site reaction or systemic reaction\n•Pfizer and GSK Guillain Barre syndrome (GBS) risk updated based on FDA active surveillance \nthrough partnership with CMS, Medicare beneficiaries ages ≥65 years1, vaccinations during \nMay –October 8, 2023:\n•Pfizer: 16 GBS cases (95% CI 3 –29) per 1 million doses administered2\n•GSK: 3 GBS cases (95% CI 0 –10) per 1 million doses administered2,3\n•Moderna data based on trial\n•Moderna: 7% experienced severe  injection site reaction or systemic reaction\n•Assumed no vaccine -attributable GBS risk\n•All Vaccines: rare, unnamed serious adverse event of 1 per million doses administered\n15Methods: Adverse Events\nAbbreviations: CI = confidence interval, CMS = Centers for Medicare & Medicaid Services, FDA = U.S. Food and Drug Administrat ion, GBS = Guillain -Barre \nsyndrome\n1.Must have been enrolled in Medicare Parts A, B and D. Must not have had a diagnostic code for GBS in the 365 days preceding v accination.\n2.These estimates reflect vaccine -attributable risk of GBS in excess of background rate of GBS among adults ages ≥65 years vaccina ted with the same product. \nThis analysis extrapolated from the study population and assumed the same risk applied to adults ages 50 –64 years.\n3.Attributable risk for GSK’s AREXVY was estimated to be 3 GBS cases (95% CI: -3, 10) per 1 million doses. For mathematical modeling , lower end of the 95% CI \nwas truncated at 0 to evaluate potential risk  of GBS. Potential protective effects were not evaluated.\nMethods: Base RSV Medical Costs\nVariable Value Range Source\nDisease -specific hospitalization costs (per hospitalization)\nage 50 to <60 years $20,330 9,511 – 39,544\nAckerson 2020*age 60 to <65 years $21,417 9,288 – 45,454\nage 65 to <75 years $21,417 10,491 – 43,619\nage ≥75 years $22,425 10,491 – 43,619\nDisease -specific ED costs (per ED visit) \nage 60 to <65 years $1,210 -\n2016 Marketscan* age 65 to <75 years $1,210 -\nage ≥75 years $1,210 -\nDisease -specific outpatient costs (per outpatient visit) \nage 60 to <65 years $117.58 65.88 -145.38MarketScan  and Medicare FFS, \n2020 -2021age 65 to <75 years $100.86 50.48 -120.08\nage ≥75 years $100.86 50.48 -120.08\n16\n*Updated to 2023 using GDP Deflator\nMethods: Hospitalization cost multiplier based on chronic \nmedical conditions\n17Condition Condition -specific multiplier, based on median length of stay (RSV -NET)\nAt least one condition* 1.06\nWith COPD 1.22\nWith Asthma 1.0\nWith CAD 1.13\nWith Diabetes 1.11\nWith severe obesity, BMI ≥40 1.0\nWith CKD 1.26\nNone of these conditions** 0.84\nWith Heart Failure 1.28\nImmune Compromise 1.06\n*Have at  least one of: chronic obstructive pulmonary disease, asthma, coronary artery disease, diabetes mellitus, severe obesity (BMI ≥40), chronic kidney \ndisease; may also have other conditions such as heart failure or immune compromise\n** None of the conditions in the at least one definition, but may have other conditions such as heart failure or immune compr omise\nMethods: Vaccination -Related Costs\nVariable Value Range Source\nVaccine, per dose\nPfizer $295 List price\nGSK $280 List price\nModerna $290 Manufacturer Assumption\nVaccine administration $16.96 -HCPCS 90460 (Physician Fee Schedule \n2022)\n18\nMethods: Additional Inputs\n•Also included \n•RSV illness QALYs lost\n•RSV illness productivity costs\n•Vaccination healthcare and productivity costs\n•Vaccination adverse events\n•Medical costs\n•Productivity costs\n•These assumptions remain unchanged from October 2023\n19* DW Hutton, “Economic Analysis of RSV Vaccination in Older Adults” June 21, 2023 (cdc.gov)\nMethods: Scenarios\n•Manufacturer -specific (Pfizer and GSK -specific models; Moderna is \nconsidered separately in the base case, so no scenario needed)\n•Assuming longer duration of protection (efficacy declines to 0 at 36 \nrather than at 24 months)\n•Among persons without chronic medical conditions \n•Condition -specific (e.g., among persons with heart failure)\n20\nBase case results\n21\nBase case Incremental Cost -Effectiveness \nRatios ($/QALY)\nProtein subunit RSV \nvaccines\n(combined Pfizer + GSK)Moderna RSV vaccine\nAll adults 75+ $              51,447  $              66,287  \nAdults 60 -74 with at \nleast 1 condition1 $              60,933  $              80,953  \nAdults 50 -59 with at \nleast 1 condition1,2 $           154,501  \n1. At least one of: chronic obstructive pulmonary disease, asthma, coronary artery disease, diabetes mellitus, chronic \nkidney disease, severe obesity (BMI ≥40)  \n2. Only a single vaccine (GSK AREXVY) is licensed in adults 50 -59. So, this uses GSK -specific input parameters for this \nage group.\nBMI: body mass index, QALY: Quality -Adjusted Life -Year 22\nIncremental Cost -Effectiveness\nQALY: Quality -Adjusted Life -Year\n23At least one of: chronic obstructive pulmonary disease, asthma, coronary artery disease, diabetes mellitus, chronic kidney di sease, severe obesity \n(BMI ≥40)Protein subunit vaccine All \nadults ≥75\n $- $500 $1,000 $1,500 $2,000 $2,500 $3,000\n -  5  10  15  20  25  30  35  40Incremental Societal Costs (Millions)\nIncremental QALYs Saved (Thousands)\nIncremental Cost -Effectiveness\nQALY: Quality -Adjusted Life -Year\n24At least one of: chronic obstructive pulmonary disease, asthma, coronary artery disease, diabetes mellitus, chronic kidney di sease, severe obesity \n(BMI ≥40)Protein subunit vaccine All \nadults ≥75 $51,447/QALY\n $- $500 $1,000 $1,500 $2,000 $2,500 $3,000\n -  5  10  15  20  25  30  35  40Incremental Societal Costs (Millions)\nIncremental QALYs Saved (Thousands)\nIncremental Cost -Effectiveness\nQALY: Quality -Adjusted Life -Year\n25At least one of: chronic obstructive pulmonary disease, asthma, coronary artery disease, diabetes mellitus, chronic kidney di sease, severe obesity \n(BMI ≥40)Protein subunit vaccine All \nadults ≥75Protein subunit vaccine All \nadults ≥75 AND 60 -74 with at \nleast 1 condition\n$51,447/QALY$60,933/QALY\n $- $500 $1,000 $1,500 $2,000 $2,500 $3,000\n -  5  10  15  20  25  30  35  40Incremental Societal Costs (Millions)\nIncremental QALYs Saved (Thousands)\nIncremental Cost -Effectiveness\nQALY: Quality -Adjusted Life -Year\n26At least one of: chronic obstructive pulmonary disease, asthma, coronary artery disease, diabetes mellitus, chronic kidney di sease, severe obesity \n(BMI ≥40)Protein subunit vaccine All \nadults ≥75Protein subunit vaccine All \nadults ≥75 AND 60 -74 with at \nleast 1 conditionProtein subunit vaccine All \nadults ≥75 AND 60 -74 with at \nleast 1 condition AND 50 -59 \nwith at least 1 condition\n$51,447/QALY$60,933/QALY$154,501/QALY\n $- $500 $1,000 $1,500 $2,000 $2,500 $3,000\n -  5  10  15  20  25  30  35  40Incremental Societal Costs (Millions)\nIncremental QALYs Saved (Thousands)\nIncremental Cost -Effectiveness\nQALY: Quality -Adjusted Life -Year\n27At least one of: chronic obstructive pulmonary disease, asthma, coronary artery disease, diabetes mellitus, chronic kidney di sease, severe obesity \n(BMI ≥40)Protein subunit vaccine All \nadults ≥75Protein subunit vaccine All \nadults ≥75 AND 60 -74 with at \nleast 1 conditionProtein subunit vaccine All \nadults ≥75 AND 60 -74 with at \nleast 1 condition AND 50 -59 \nwith at least 1 condition\nModerna vaccine All adults ≥75\n$51,447/QALY$60,933/QALY$154,501/QALY\n$66,287/QALY\n $- $500 $1,000 $1,500 $2,000 $2,500 $3,000\n -  5  10  15  20  25  30  35  40Incremental Societal Costs (Millions)\nIncremental QALYs Saved (Thousands)\nIncremental Cost -Effectiveness\nQALY: Quality -Adjusted Life -Year\n28At least one of: chronic obstructive pulmonary disease, asthma, coronary artery disease, diabetes mellitus, chronic kidney di sease, severe obesity \n(BMI ≥40)Protein subunit vaccine All \nadults ≥75Protein subunit vaccine All \nadults ≥75 AND 60 -74 with at \nleast 1 conditionProtein subunit vaccine All \nadults ≥75 AND 60 -74 with at \nleast 1 condition AND 50 -59 \nwith at least 1 condition\nModerna vaccine All adults ≥75Moderna vaccine All adults ≥75 \nAND 60 -74 with at least 1 \ncondition\n$51,447/QALY$60,933/QALY$154,501/QALY\n$66,287/QALY$80,953/QALY\n $- $500 $1,000 $1,500 $2,000 $2,500 $3,000\n -  5  10  15  20  25  30  35  40Incremental Societal Costs (Millions)\nIncremental QALYs Saved (Thousands)\nScenario analyses \n29\nProtein subunit RSV vaccination: product -\nspecific\nGSK AREXVY Pfizer ABRYSVO\nAll adults 75+ $        47,050  $        58,739  \nAdults 60 -74 with at \nleast 1 condition$        55,006  $        70,624  \n30At least one of: chronic obstructive pulmonary disease, asthma, coronary artery disease, diabetes mellitus, \nchronic kidney disease, severe obesity (BMI ≥40)\nTime Horizon Comparison\nBase case  (24 months of efficacy )\nProtein subunit RSV \nvaccines\n(combined Pfizer + \nGSK)Moderna RSV \nvaccineProtein subunit RSV \nvaccines\n(combined \nPfizer+GSK )Moderna RSV \nvaccine\nAll adults 75+ $              51,447  $              66,287  $              39,833  $              42,495  \nAdults 60 -74 \nwith at least 1 \ncondition$              60,933  $              80,953  $              45,445  $              49,198  \nAdults 50 -59 \nwith at least 1 \ncondition*$           154,501  $           112,949  Scenario  (36 months of efficacy )\n*Only a single manufacturer (GSK) has applied for FDA licensure in adults 50 -59. So, this scenario uses GSK -specific inputs.\n31At least one of: chronic obstructive pulmonary disease, asthma, coronary artery disease, diabetes mellitus, chronic kidney di sease, \nsevere obesity (BMI ≥40)\nCost -Effectiveness by age and conditions\n* At least one of: chronic obstructive pulmonary disease, asthma, coronary artery disease, diabetes mellitus, chronic kidney disease, severe obesity (BMI ≥40)  \n** None of the above conditions. Persons may have other chronic medical conditions (e.g., heart failure, non -severe obesity, imm une compromise).32$14,636 $60,933 $154,501 \n$22,905 $80,953 $168,075 $505,385 \n$202,918 $608,761 \n $- $100,000 $200,000 $300,000 $400,000 $500,000 $600,000 $700,000\nAdults ≥75  Adults 60-74 Adults 50-59 Adults ≥75  Adults 60-74\nProtein subunit vaccine GSK Moderna vaccineICER ($ per QALY gained)\nAt least one condition* None of these conditions**\nScenarios: Cost -effectiveness of vaccinating adults with \nspecific chronic conditions \nProtein subunit RSV \nvaccines\n(combined Pfizer+GSK )Moderna RSV vaccine\nAdults 60 -74 with specific \nconditions : heart failure, \nimmune compromise, \nCOPD, asthma, CAD, \ndiabetes, severe obesity, \nchronic kidney disease10 Scenarios 10 Scenarios\nAdults 50 -59 with specific \nconditions : as above10 Scenarios\n(GSK -specific)*\n*Only a single vaccine (GSK AREXVY) is licensed in adults 50 -59. So, this uses GSK -specific inputs for this age group.33\n$0 $25,000 $50,000 $75,000 $100,000 $125,000 $150,000 $175,000 $200,000\nAll Adults\nAt least one condition\n CKD\n COPD\n obesity BMI >40\n Asthma\n CAD\n Diabetes\nNone of the above…\n Heart Failure\nWith lung transplant\nWith allogenic HCT\nWith autologous HCTIncremental cost effectiveness ratio ($ per QALY gained)\n 50-59\n 60-74\n≥75Scenarios: Adults with specific chronic medical conditions, protein subunit RSV \nvaccines (Pfizer/GSK)\n*Indicates cost saving\nAt least one condition refers to: COPD, asthma, coronary artery disease, diabetes \nmellitus, chronic kidney disease, severe obesity (BMI ≥40)//$505,385**\n*Adults 50 -59 without chronic conditions are not under consideration\nAdults 50 -59 without chronic conditions are not under consideration\n*\n**\n†Only a single vaccine (GSK AREXVY) is licensed in adults 50 -59. So, this uses GSK -specific inputs for \nthis age group.\nHCT: Hematopoietic Cell Transplant†\n$0 $25,000 $50,000 $75,000 $100,000 $125,000 $150,000 $175,000 $200,000\nAll Adults\nAt least one condition\n CKD\n COPD\n obesity BMI >40\n Asthma\n CAD\n Diabetes\nNone of the above…\n Heart Failure\nWith lung transplant\nWith allogenic HCT\nWith autologous HCTIncremental cost effectiveness ratio ($ per QALY gained)\n 60-74\n≥75Scenarios: Adults with specific chronic medical conditions, Moderna RSV vaccine\n*\n*\n//$608,761\n//$202,918//$217,582\n*\n*\n*\n*Indicates cost saving\nAt least one condition refers to: COPD, asthma, coronary artery disease, diabetes mellitus, chronic kidney disease, severe ob esity (BMI ≥40)\nHCT: Hematopoietic Cell Transplant\nSensitivity Analysis: \nChanging Parameter Assumptions\n36\nGSK RSV vaccine at least 1 condition age 50 -59\n37$0 $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000\nIncidence of RSV hospitalization\nRSV-attributable mortality\nRSV QALYs Lost Outpatient Adult\nCost per Hospitalization\nVE GSK Hospitalized months 13-23\nVE GSK Outpatient months 13-23\nHealth Utility Age 60-69 years\nVE GSK Hospitalized months 0-7\nIncidence of outpatient visits for RSV\n GBS Cases per MillionIncremental Cost -Effectiveness Ratio ($/QALY gained)As least one condition Age 50 -59 years GSK\nLow Assumption High Assumption\nLimitations\n•Model Structure\n•No dynamic transmission. No impact of the vaccine on transmission and indirect \neffects\n•We did not include or analyze all potential RSV risk factors.  \n•Some medical conditions (e.g., interstitial lung disease) are likely associated with \nhigh risk of severe RSV disease, but literature on population -based hospitalization \nrates and other outcomes are lacking.  \n•RSV vaccination may be cost effective for adults with additional conditions that were \nnot evaluated.\n•Uncertain inputs\n•Moderna real -world vaccine effectiveness\n•Moderna vaccine cost \n•RSV burden of disease, especially hospitalization and mortality\n•Duration and waning pattern of vaccine protection\n38\nConclusions\n•If there were a recommendation for RSV vaccination for all adults 75 and older the ICER \nwould be $51,447 societal cost/QALY saved (Pfizer/GSK) and $66,287/QALY (Moderna) . \n•If instead we limited the recommendation only to adults 75 and older with at least one chronic \nmedical condition the ICER would be $14,636/QALY (Pfizer/GSK) and $22,905 (Moderna)\n•If we add in adults 60-74 with at least one chronic medical condition , the ICER would be \n$60,933 societal cost/QALY (Pfizer/GSK) and $80,953/QALY (Moderna) . \n•Vaccination of adults 60 -74 without  chronic conditions has an ICER of $505,385/QALY (Pfizer/GSK) \nand $608,761/QALY (Moderna)\n•If we add in adults 50-59 with at least one chronic medical condition the ICER would be \n$154,501 societal cost/QALY saved (GSK only). \n•By specific condition, $/QALY saved was lowest among adults 50 -59 with heart failure \n($14,335/QALY ) and immune compromise ( cost-saving or $14,521/QALY ) and highest among \nthose with diabetes ($171,661/QALY ).\n•Longer duration of protection (36 months rather than 24 months) or higher baseline RSV \ndisease burden made all policy options more cost effective.\n39\nThank You\n•Please send comments to:\n•dwhutton@umich.edu\n40\n41Methods: Epidemiology\nRSV Hospitalization Incidence by Age and Chronic Medical \nCondition “back -up slide not shown at meeting\"\nSource: CDC RSV -NET data from RSV seasons: 2016 -17, 2017 -18, 2018 -19, 2019 -2020\n* At least one of: chronic obstructive pulmonary disease, asthma, coronary artery disease, diabetes mellitus, chronic kidney disease, severe obesity (BMI ≥40)  \n** None of the above conditions. Persons may have other chronic medical conditions (e.g., heart failure, non -severe obesity, imm une compromise).050010001500200025003000350040004500RSV-associated Hospitalizations \nper 100,000\nAge 50-59 years Age 60-74 years Age ≥75 years", "summary": "Economic Analysis of RSV Vaccination  in Adults 50 years and Older David W. Hutton, PhD, MS Associate Professor, Health Management and Policy, School of Public Health Associate Professor of Global Public Health, School of Public Health Associate Professor, Industrial and Operations Engineering, College of Engineering University of Michigan 1 Research Team University of Michigan •David Hutton, PhD •Lisa Prosser, PhD •Angela Rose, MPH •Christina Nyamuswa , MSCDC •Michael Melgar, MD •Amadea…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/08-RSV-Adult-Hutton-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 41}
{"title": "09 RSV Adult Hutton 508", "content": "Risk-Benefit Analysis of RSV \nVaccination in Older Adults \nDavid W. Hutton, PhD, MS\nAssociate Professor, Health Management and Policy, School of Public Health\nAssociate Professor of Global Public Health, School of Public Health\nAssociate Professor, Industrial and Operations Engineering, College of Engineering\nUniversity of Michigan\n1This presentation has been corrected. See slides 13, 20, and 21 for corrected slides. The original slides are included at the  end of the presentation.\nDisclaimer\n•An error in the market productivity calculation for adults aged 50 –6 4 \nyears has been identified in this presentation.\n•Correction of this error and additional updates have been \ninc\norporated into a more recent analysis.\n•Please refer to the ACIP agenda on Ap ril 16, 2025  and the \npresentation titled, “Economic Analysis of Adult RSV Vaccination, including benefits and risk discussion” by Dr. Ismael Ortega -Sanchez \nfor the most updated version of this analysis.\n2\nResearch Team\nUniversity of Michigan\n•David Hutton, PhD\n•Lisa Prosser, PhD\n•Angela Rose, MPH\n•Christina Nyamuswa , M SCDC\n•Michael Melgar , M D\n•Amadea Britton, MD \n•Lauren Roper, MPH\n•Mila P rill, M SPH\n•Jamison Pike, PhD\n•Ismael Ortega- Sa nchez, PhD\n•Andrew Leidner, PhD\n•Fiona Havers, MD\n•Michael Whitaker, MPH\n•Rebecca Woodruff, PhD\n•Huong Pham, MPH\n3\nConflicts of interest  statements\n•No known conflict of interests.\n4\nObjective: \n•Compare the es timated benefits of RSV vaccination with the potential risk of Guillain -\nBarre syndrome (GBS) after RSV vaccination in adults aged 50 -59 years with chronic \nmedical conditions, 60 -74 years with chronic medical conditions, and among all adults \naged 75 years and older.\n•To do this, used the same mathematical models presented in previous presentation. In \nad\ndition to cost effectiveness, these models estimate the burden of RSV disease, \nincluding RSV -associated hospitalization, ICU admissions, and deaths, that might be \naverted through vaccination. \n•Will summarize estimated benefit outputs from those models and add information on \npot\nential rates of GBS experienced after RSV vaccination.\n•This is an update to the presentation on benefits and risks from the February 2024 ACIP \nmee\nting. Here, we add information on observational (“real -world”) vaccine effectiveness \nagainst hospitalization and expand the analysis to evaluate benefits and risks specifically among adults with chronic medical conditions, including adults aged 50 -59 years. \n•Focus only on the Pr\n otein subunit RSV vaccines (manufactured by Pfizer and GSK). To date, \nthere are no pre -licensure or observational data indicating risk of GBS after Moderna RSV \nvaccination (mRESVIA). 5\nMethods: Study question\n•Compare the es timated benefits of RSV vaccination and the \npotential risk of Guillain -Barre syndrome (GBS)  after Protein \nsubunit RSV vaccination (Pfizer/GSK).\n6\nMethods: Intervention(s)\n•Target population: US adults aged ≥50 years, stratified by age, \nchronic medical conditions\n•Adults aged ≥75 years\n•Adults aged 60 -74  years with at least one chronic medical condition*\n•Adults aged 50 -59  years with at least one chronic medical condition*\n•Interventions: Pro tein subunit RSV vaccines\n•Pfizer’s ABRYSVO\n•GSK’s AREXVY\n•Comparator: Ea ch compared to No Vaccination\n7*At least one of: chronic obstructive pulmonary disease (COPD), asthma, coronary artery disease, chronic kidney disease, \ndiabetes mellitus, severe obesity (BMI ≥40)\nMethods: Scenario analyses\n•Adults in each age group (50 -59, 60 -74, ≥75) without chronic medical \nconditions*\n•Adults in each age group with sp ecific  chronic medical conditions:\n•Chronic obstructive pulmonary disease (COPD)\n•Asthma\n•Coronary artery disease\n•Chronic kidney disease\n•Diabetes mellitus\n•Severe obesity (BMI ≥40 )\n•Heart failure \n•Immune Compromise\n•Lung Transplant\n•Hematopoietic cell transplant, allogeneic\n•Hematopoietic cell transplant, autologous\n8Assumed that vaccine effectiveness was \nreduced by half in immune compromised \npopulations, compared with all others\n*None of: COPD, asthma, coronary artery disease, chronic kidney disease, diabetes mellitus, severe obesity (BMI ≥40)\nHeart failure and immune compromise are considered separately because RSV epidemiologic parameters were derived from differen t \npublished sources and cannot be combined with RSV -NET hospitalization rate estimates under “at least one” condition.\nMethods: Decision Tree Model\n9No \nVaccination\nVaccinationInfection Hospitalization\nED\nNone of the aboveOutpatientAlive\nDeadRSV Infection\nAdverse \nEventsGuillain Barre Syndrome\nNo Guillain Barre SyndromeInfection RSV Infection\n•GBS risk attributable to RSV vaccination is based on FDA active surveillance \nusing CMS data. \n•The FDA analysis was a self -controlled case series based on inpatient claims \ndata.\nStudy population: Medicare beneficiaries ages ≥65 years1 who had received either Pfizer or \nGSK RSV vaccine, from May 2023 (date of FDA approval) to October 8, 2023\nUsed administrative inpatient claims data to identify GBS cases occurring within a 1– 42-day \nrisk interval after RSV vaccination, compared with a 43 –90-day control interval\nIncidence rate ratios and attributable risk were adjusted for outcome-dependent observation time, positive predictive value of inpatient claims in identifying chart -confirmed GBS, and \nseasonality\n10Methods: Attributable Risk of Guillain Barre Syndrome (GBS) from \nRSV vaccination \nAbbreviations: CMS = Centers for Medicare & Medicaid Services, FDA = U.S. Food and Drug Administration, GBS = Guillain -Barre syndrome\n1. Must have been enrolled in Medicare Parts A, B and D. Must not have had a diagnostic code for GBS in the 365 days preceding v accination. \nReference (Dr. Patricia Lloyd, FDA, June 2024 ACIP meeting)\n•Attributable risk of GBS:\nPfizer ABRYSVO : 16 GBS cases (95% CI: 3, 29) per 1 million doses administered\nGSK AREXVY : 3 GBS cases (95% CI: 0, 10) per 1 million doses administered*\n•These risk estimates are in excess of  background rate of GBS. I.e., they \nrepresent excess GBS cases beyond those that would occur in this \npopulation without vaccination. \n•This analysis remains preliminary. GBS cases identified using diagnostic coding must still undergo chart verification, and the analysis must be updated to include RSV vaccinations occurring after October 8, 2023. \n•In the interim, we are using the available estimates, recognizing the associated uncertainty. We are also extrapolating from the study population (age ≥65 years) to adults aged 50 –64 years.\n11Methods: Attributable Risk of Guillain Barre Syndrome (GBS) from \nRSV vaccination \nAbbreviations: CI = confidence interval, CMS = Centers for Medicare & Medicaid Services, FDA = U.S. Food and Drug Administrat ion, GBS = Guillain -Barre syndrome\n* At tributable risk for GSK’s AREXVY was estimated to be 3 GBS cases (95% CI: -3, 10) per 1 million doses. For this analysis, the lo wer end of the 95% CI was \ntruncated at 0 to evaluate potential risk  of GBS. Potential protective effects were not evaluated.\n•Results are presented as R SV outcomes avertable over 2 RSV seasons \nper 1 million single- dose RSV vaccinations , and attributable GBS risk \nper 1 million single- dose RSV vaccinations .\n12Results: Estimated Benefits and Potential Risk\n3 GBS cases \n(95% CI 0– 10) Estimated RSV- associated outcomes avertable over 2 \nRSV seasons vs. potential cases of GBS per 1 million \nvaccine doses in adults ≥75 years (general population)\n16 GBS cases \n(95% CI 3– 29) 4,283\n13630 605\n01,0002,\n0003,0004,0005,0006,0007,0008,000Events AvertedGSK All Adults Age ≥75\nHospitalization ICU Stays Death3,817\n561 539\n08,0\n7,000ed6,000t er5,000v A  s4,000t en3,000v E2,0001,000Pfizer All Adults Age ≥75\n00\nHospitalization ICU Stays Death202 329 190 283 Lower Bound:This slide contains corrections. To see the slide as originally presented, without corrections, please see slide 32.\nEstimated RSV- associated outcomes avertable over 2 RSV \nseasons vs. potential cases of GBS per 1 million vaccine \ndoses in adults 60 -74 years with ≥1 chronic condition*\n14*At least one of: chronic obstructive pulmonary disease, asthma, coronary artery disease, diabetes mellitus, chronic kidney \ndisease, severe obesity (BMI ≥40)  3 GBS cases \n(95% CI 0– 10) 16 GBS cases (95% CI 3– 29) \n2,839\n647246\n02,0004,0006,0008,000Events AvertedGSK At least one condition Age \n60-74 years\nHospitalization ICU Stays Death2,530\n577219\n02,0004,0006,0008,000Events AvertedPfizer At least one condition Age \n60-74 years\nHospitalization ICU Stays Death83 337 74 311 Lower Bound:\nEstimated RSV- associated outcomes avertable over 2 RSV \nseasons vs. potential cases of GBS per 1 million vaccine \ndoses in adults 50 -59 years with ≥1 chronic condition*\n15*At least one of: chronic obstructive pulmonary disease, asthma, coronary artery disease, diabetes mellitus, chronic kidney \ndisease, severe obesity (BMI ≥40)  3 GBS cases \n(95% CI 0– 10) \n1,520\n33183\n02,0004,0006,0008,000Events AvertedGSK At least one condition Age \n50-59 years\nHospitalization ICU Stays Death26 130Lower Bound:\n16*At least one of: chronic obstructive pulmonary disease, asthma, coronary artery disease, diabetes mellitus, chronic kidney \ndisease, severe obesity (BMI ≥40)  3 GBS cases \n(95% CI 0– 10) \nZoomed In1,520\n331\n83\n05001,0001,5002,000Events AvertedGSK At least one condition Age \n50-59 years\nHospitalization ICU Stays DeathEstimated RSV- associated outcomes avertable over 2 RSV \nseasons vs. potential cases of GBS per 1 million vaccine \ndoses in adults 50 -59 years with ≥1 chronic condition*\nRange \n199 -26\n26130\nLower Bound:\nScenarios\n17\nScenario 1: Estimated RSV-associated outcomes \navertable among adults without  chronic medical \nconditions*\n18*None of: COPD, asthma, coronary artery disease, chronic kidney disease, diabetes mellitus, severe obesity \n(BMI ≥40)\nEstimated RSV- associated outcomes avertable over 2 RSV \nseasons vs. potential cases of GBS per 1 million vaccine \ndoses in adults ≥75 years with none of these conditions *\n19*None of: COPD, asthma, coronary artery disease, chronic kidney disease, diabetes mellitus, severe obesity (BMI ≥40). \nPersons may have other chronic medical conditions (e.g., heart failure, non- severe obesity, immune compromise).3 GBS cases \n(95% CI 0– 10) 16 GBS cases (95% CI 3– 29) \n1,732\n189 245\n02,0004,0006,000Events AvertedGSK None of these conditions \nAge ≥75\n8,000\nHospitalization ICU Stays Death1,544\n168 218\n02,0004,0006,0008,000Events AvertedPfizer None of these conditions \nAge ≥75\nHospitalization ICU Stays Death84 89 73 80 Lower Bound:\n40664 35\n02,0004,0006,0008,000Events AvertedPfizer None of these conditions \nAge 60 -74 years\nHospitalization ICU Stays DeathEstimated RSV- associated outcomes avertable over 2 RSV \nseasons vs. potential cases of GBS per 1 million vaccine \ndoses in adults 60 -74 years with none of these conditions *\n20*None of: COPD, asthma, coronary artery disease, chronic kidney disease, diabetes mellitus, severe obesity (BMI ≥40).\nPersons may have other chronic medical conditions (e.g., heart failure, non- severe obesity, immune compromise).3 GBS cases \n(95% CI 0– 10) 16 GBS cases (95% CI 3– 29) \n45672 39\n02,0004,0006,0008,000Events AvertedGSK None of these conditions \nAge 60 -74 years\nHospitalization ICU Stays DeathLower \nBound 14\n16 14 39 34 Lower Bound:Lower \nBound 16This slide contains corrections. To see the slide as originally presented, without corrections, please see slide 34.\n406\n6435\n0100200300400500Events AvertedPfizer None of these conditions \nAge 60 -74 years\nHospitalization ICU Stays Death\n21*None of: COPD, asthma, coronary artery disease, chronic kidney disease, diabetes mellitus, severe obesity (BMI ≥40).\nPersons may have other chronic medical conditions (e.g., heart failure, non- severe obesity, immune compromise).3 GBS cases \n(95% CI 0– 10) 16 GBS cases (95% CI 3– 29) \nLower \nBound 14Zoomed InEstimated RSV- associated outcomes avertable over 2 RSV \nseasons vs. potential cases of GBS per 1 million vaccine \ndoses in adults 60 -74 years with none of these conditions*\n456\n7239\n0100200300400500Events AvertedGSK None of these conditions \nAge 60 -74 years\nHospitalization ICU Stays Death1639 1434\nLower Bound:Lower \nBound 16This slide contains corrections. To see the slide as originally presented, without corrections, please see slide 36.\nScenario 2: RSV-attributable deaths  avertable \namong adults by age and presence of specific  \nchronic conditions\n22\n1,0441,6431,472\n890 8041,6612,468\n4491,146\n443\n01,0002,0003,0004,0005,0006,0007,0008,000\nAge 60-74 years\nAge ≥75\nAge 60-74 years\nAge ≥75\nAge 60-74 years\nAge ≥75\nAge 60-74 years\nAge ≥75\nAge 60-74 years\nAge ≥75\nAge 60-74 years\nAge ≥75\nAge 60-74 years\nAge ≥75\nLung Transplant\nAllogenic HCT\nAutologous HCT\nHeart Failure COPD Asthma CAD Diabetes obesity BMI >40 CKD Immune CompromiseDeahts AvertedEstimated RSV -associated deaths avertable over 2 RSV seasons vs. \npotential cases of GBS per 1 million Pfizer ABRYSVO doses in adults 75 \nyears and older with specific chronic conditions\n2316 GBS cases \n(95% CI 3– 29) Immune Compromise is not age -stratifiedHCT: hematopoietic cell transplant\nLower bound is labeled if <50\n544384 306 260 2153915854491,146\n443\n01,0002,0003,0004,0005,0006,0007,0008,000\nAge 60-74 years\nAge ≥75\nAge 60-74 years\nAge ≥75\nAge 60-74 years\nAge ≥75\nAge 60-74 years\nAge ≥75\nAge 60-74 years\nAge ≥75\nAge 60-74 years\nAge ≥75\nAge 60-74 years\nAge ≥75\nLung Transplant\nAllogenic HCT\nAutologous HCT\nHeart Failure COPD Asthma CAD Diabetes obesity BMI >40 CKD Immune CompromiseDeaths AvertedEstimated RSV -associated deaths avertable over 2 RSV seasons \nvs. potential cases of GBS per 1 million Pfizer ABRYSVO doses in \nadults 60-74 years with specific chronic conditions\n2416 GBS cases \n(95% CI 3– 29) Immune Compromise is not age -stratifiedHCT: hematopoietic cell transplant\nLower bound is labeled if <50\n1,1711,8431,652\n999 902\n1334391,8642,769\n5031,286\n497\n01,0002,0003,0004,0005,0006,0007,0008,000\nAge 50-59 years\nAge 60-74 years\nAge ≥75\nAge 50-59 years\nAge 60-74 years\nAge ≥75\nAge 50-59 years\nAge 60-74 years\nAge ≥75\nAge 50-59 years\nAge 60-74 years\nAge ≥75\nAge 50-59 years\nAge 60-74 years\nAge ≥75\nAge 50-59 years\nAge 60-74 years\nAge ≥75\nAge 50-59 years\nAge 60-74 years\nAge ≥75\nLung Transplant\nAllogenic HCT\nAutologous HCT\nHeart Failure COPD Asthma CAD Diabetes obesity BMI >40 CKD Immune\nCompromiseDeaths AvertedEstimated RSV -associated deaths avertable over 2 RSV seasons \nvs. potential cases of GBS per 1 million GSK AREXVY doses in \nadults 75 years and older with specific chronic conditions\n253 GBS cases \n(95% CI 0– 10) Immune Compromise is not age -stratifiedHCT: hematopoietic cell transplant\nLower bound is labeled if <50\n610431 344 292 241 1334391,864\n6575031,286\n497\n01,0002,0003,0004,0005,0006,0007,0008,000\nAge 50-59 years\nAge 60-74 years\nAge ≥75\nAge 50-59 years\nAge 60-74 years\nAge ≥75\nAge 50-59 years\nAge 60-74 years\nAge ≥75\nAge 50-59 years\nAge 60-74 years\nAge ≥75\nAge 50-59 years\nAge 60-74 years\nAge ≥75\nAge 50-59 years\nAge 60-74 years\nAge ≥75\nAge 50-59 years\nAge 60-74 years\nAge ≥75\nLung Transplant\nAllogenic HCT\nAutologous HCT\nHeart Failure COPD Asthma CAD Diabetes obesity BMI >40 CKD Immune\nCompromiseDeaths AvertedEstimated RSV -associated deaths avertable over 2 RSV seasons \nvs. potential cases of GBS per 1 million GSK AREXVY doses in \nadults 60-74 years with specific chronic conditions\n263 GBS cases \n(95% CI 0– 10) Immune Compromise is not age -stratifiedHCT: hematopoietic cell transplant\nLower bound is labeled if <50\n278133 95 98 75 1334391,864\n2305031,286\n497\n01,0002,0003,0004,0005,0006,0007,0008,000\nAge 50-59 years\nAge 60-74 years\nAge ≥75\nAge 50-59 years\nAge 60-74 years\nAge ≥75\nAge 50-59 years\nAge 60-74 years\nAge ≥75\nAge 50-59 years\nAge 60-74 years\nAge ≥75\nAge 50-59 years\nAge 60-74 years\nAge ≥75\nAge 50-59 years\nAge 60-74 years\nAge ≥75\nAge 50-59 years\nAge 60-74 years\nAge ≥75\nLung Transplant\nAllogenic HCT\nAutologous HCT\nHeart Failure COPD Asthma CAD Diabetes obesity BMI >40 CKD Immune\nCompromiseDeaths AvertedEstimated RSV -associated deaths avertable over 2 RSV seasons \nvs. potential cases of GBS per 1 million GSK AREXVY doses in \nadults 50-59 years with specific chronic conditions\n273 GBS cases \n(95% CI 0– 10) Immune Compromise is not age -stratifiedHCT: hematopoietic cell transplant\nLower bound is labeled if <5042 31 30 25 38Lower Bound:\nSummary\n•Estimated numbers of avertable deaths are much larger than \np\notential GBS cases for:\n•Adults 75 and older\n•Adults 60 -7 4 with at least one chronic condition\n•Estimated numbers of avertable hospitalizations and ICU admissions a\nre much larger than potential GBS cases for all age groups, for both \nGSK’s AREXVY and Pfizer’s ABRYSVO.\n•Estimated numbers of avertable deaths are larger, but more similar in m\nagnitude, than potential GBS cases for:\n•Adults 50 -5 9 with at least one chronic condition\n•Adults 60 -7 4 without chronic conditions, particularly for the Pfizer ABRYSVO \nvaccine\n28\nLimitations\n•Uncertain Inputs\n•RSV hospitalization incidence by age and condition\n•RSV-NET represents ~9% of the United States and hospitalization rates observed in RSV -N ET may \nnot be generalizable to the U.S.\n•Could not include all conditions that may increase risk of severe RSV disease in this analysis\n•Vaccine effectiveness (VE)\n•Observational VE data only available for first few months after vaccination —p rotection over time \nwas extrapolated from waning in efficacy against symptomatic illness observed in clinical trials\n•Risk of Guillain-Barre Syndrome\n•GBS risk estimates were calculated using a small number of events observed after RSV \nva\nccination, resulting in high uncertainty.\n•GBS was identified by diagnostic codes in administrative data and may be subject to coding er\nrors. Not all cases of GBS occurring after RSV vaccination may have received a diagnostic code.\n•Attributable risk of GBS may be different among adults 50 -59  than among adults 60 and older. \n29\nThank You\n•Please send comments to:\n•dwhutton@umich.edu\n30\nOriginal slides \n•The following slides contain errata. They are being shared here for \narec\nord of what was presented at the June 26, 2024, ACIP meeting.\n•Corrected slides are available in the main presentation.\n•Corrected slides with changes highlighted are included in th\nefollowing slides.\n31\n3 GBS cases \n(95% CI 0– 10) Estimated RSV- associated outcomes avertable over 2 \nRSV seasons vs. potential cases of GBS per 1 million \nvaccine doses in adults ≥75 years (general population)\n3216 GBS cases \n(95% CI 3– 29) 4,283\n630 605\n01,0002,0003,0004,0005,0006,0007,0008,000Events AvertedGSK All Adults Age ≥75\nHospitalization ICU Stays Death3,817\n561 539\n01,0002,0003,0004,0005,0006,0007,0008,000Events AvertedPfizer All Adults Age ≥75\nHospitalization ICU Stays Death254 311 232 295 Lower Bound:This slide was presented at ACIP on June 26, 2024 and contains errata (highlighted in purple). To see the corrected slide, pl ease see slide 13 ; to see the corrected slide with changes highlighted see slide 33.\n3 GBS cases \n(95% CI 0– 10) Estimated RSV- associated outcomes avertable over 2 \nRSV seasons vs. potential cases of GBS per 1 million \nvaccine doses in adults ≥75 years (general population)\n3316 GBS cases \n(95% CI 3– 29) 4,283\n630 605\n01,0002,0003,0004,0005,0006,0007,0008,000Events AvertedGSK All Adults Age ≥75\nHospitalization ICU Stays Death3,817\n561 539\n01,0002,0003,0004,0005,0006,0007,0008,000Events AvertedPfizer All Adults Age ≥75\nHospitalization ICU Stays Death202 329 190 283 Lower Bound:This slide has been corrected (highlighted). To see the slide as originally presented at the June 26, 2024 meeting, please se e slide 32; to see a corrected, unhighlighted version, see slide 13 .\n45672 39\n02,0004,0006,0008,000Events AvertedGSK None of these conditions \nAge 60 -74 years\nHospitalization ICU Stays DeathLower \nBound 14Lower \nBound 15\n40664 35\n02,0004,0006,0008,000Events AvertedPfizer None of these conditions \nAge 60 -74 years\nHospitalization ICU Stays DeathEstimated RSV- associated outcomes avertable over 2 RSV \nseasons vs. potential cases of GBS per 1 million vaccine \ndoses in adults 60 -74 years with none of these conditions *\n34*None of: COPD, asthma, coronary artery disease, chronic kidney disease, diabetes mellitus, severe obesity (BMI ≥40).\nPersons may have other chronic medical conditions (e.g., heart failure, non- severe obesity, immune compromise).3 GBS cases \n(95% CI 0– 10) 16 GBS cases (95% CI 3– 29) \n15 14 39 34 Lower Bound:This slide was presented at ACIP on June 26, 2024 and contains errata (highlighted in purple). To see the corrected slide, pl ease see slide 20 ; to see the corrected slide with changes highlighted see slide 35.\n45672 39\n02,0004,0006,0008,000Events AvertedGSK None of these conditions \nAge 60 -74 years\nHospitalization ICU Stays DeathLower \nBound 16\n40664 35\n02,0004,0006,0008,000Events AvertedPfizer None of these conditions \nAge 60 -74 years\nHospitalization ICU Stays DeathEstimated RSV- associated outcomes avertable over 2 RSV \nseasons vs. potential cases of GBS per 1 million vaccine \ndoses in adults 60 -74 years with none of these conditions *\n35*None of: COPD, asthma, coronary artery disease, chronic kidney disease, diabetes mellitus, severe obesity (BMI ≥40).\nPersons may have other chronic medical conditions (e.g., heart failure, non- severe obesity, immune compromise).3 GBS cases \n(95% CI 0– 10) 16 GBS cases (95% CI 3– 29) \nLower \nBound 14\n16 14 39 34 Lower Bound:This slide has been corrected (highlighted). To see the slide as originally presented at the June 26, 2024 meeting, please se e slide 34; to see a corrected, unhighlighted version, see slide 20.\nLower \nBound 15456\n7239\n0100200300400500Events AvertedGSK None of these conditions \nAge 60 -74 years\nHospitalization ICU Stays Death406\n6435\n0100200300400500Events AvertedPfizer None of these conditions \nAge 60 -74 years\nHospitalization ICU Stays Death\n36*None of: COPD, asthma, coronary artery disease, chronic kidney disease, diabetes mellitus, severe obesity (BMI ≥40).\nPersons may have other chronic medical conditions (e.g., heart failure, non- severe obesity, immune compromise).3 GBS cases \n(95% CI 0– 10) 16 GBS cases (95% CI 3– 29) \nLower \nBound 14Zoomed InEstimated RSV- associated outcomes avertable over 2 RSV \nseasons vs. potential cases of GBS per 1 million vaccine \ndoses in adults 60 -74 years with none of these conditions*\n1539 1434\nLower Bound:This slide was presented at ACIP on June 26, 2024 and contains errata (highlighted in purple). To see the corrected slide, pl ease see slide 21 ; to see the corrected slide with changes highlighted see 37.\nLower \nBound 16406\n6435\n0100200300400500Events AvertedPfizer None of these conditions \nAge 60 -74 years\nHospitalization ICU Stays Death\n37*None of: COPD, asthma, coronary artery disease, chronic kidney disease, diabetes mellitus, severe obesity (BMI ≥40).\nPersons may have other chronic medical conditions (e.g., heart failure, non- severe obesity, immune compromise).3 GBS cases \n(95% CI 0– 10) 16 GBS cases (95% CI 3– 29) \nLower \nBound 14Zoomed InEstimated RSV- associated outcomes avertable over 2 RSV \nseasons vs. potential cases of GBS per 1 million vaccine \ndoses in adults 60 -74 years with none of these conditions*\n456\n7239\n0100200300400500Events AvertedGSK None of these conditions \nAge 60 -74 years\nHospitalization ICU Stays Death1639 1434\nLower Bound:This slide has been corrected (highlighted). To see the slide as originally presented at the June 26, 2024 meeting, please se e slide 36; to see a corrected, unhighlighted version, see slide 21.", "summary": "Risk-Benefit Analysis of RSV  Vaccination in Older Adults  David W. Hutton, PhD, MS Associate Professor, Health Management and Policy, School of Public Health Associate Professor of Global Public Health, School of Public Health Associate Professor, Industrial and Operations Engineering, College of Engineering University of Michigan 1This presentation has been corrected. See slides 13, 20, and 21 for corrected slides. The original slides are included at the  end of the presentation. Disclaimer…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/09-RSV-Adult-Hutton-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 37}
{"title": "10 RSV Adult Ortega Sanchez 508", "content": "Economics of Respiratory Syncytial Virus (RSV) \nVaccination in All U.S. Adults≥75 years -old, and \nAdults aged 60 -74 and 50-59 years \nat Increased Risk\nSUMMARY COMPARING MODELS FROM:\nGSK,Moderna AND University of Michigan -CDC\nIsmael R. Ortega -Sanchez, PhD\nNCIRD/CDC\nACIP Meeting, June 26, 2024\n1Disclaimer : The findings and conclusions in this report are those of the authors and do not necessarily represent the views of \nthe Centers for Disease Control and Prevention. \nNational Center for Immunization & Respiratory Diseases\nConflict of interest\n•GSK model : David Singer et al.,  [complete list and affiliations, upon request]\n•GSK manufactures the adjuvanted RSVPreF3 vaccine \n•RTI Health Solutions was funded by GSK\n•Moderna  model : Parinaz  Ghaswalla  et al., [complete list and affiliations, upon \nrequest]\n•Moderna manufacturers the mRNA -1345 ( mRESVIA ) RSV  vaccine\n•Quadrant Health Economics was funded by Moderna\n•UM-CDC model : David W Hutton et al. from Univ Michigan, …, Ismael R Ortega -\nSanchez et al. from CDC [complete list and affiliations, upon request ]\n•All authors: No conflicts of interest\n2\nThree policy questions for economic modeling\n1.Should a single dose of RSV vaccination (any licensed product) be \nrecommended for all adults 75+?\n2.Should a single dose of RSV vaccination (any licensed product) be \nrecommended for adults 60 -74 at increased risk of severe RSV \ndisease? \n3.Should a single dose of RSV vaccination (any licensed product*) be \nrecommended for adults 50 -59 at increased risk of severe RSV \ndisease?\n*Only a single RSV vaccine (GSK AREXVY) is licensed for use in adults aged 50 -59 years who are at increased risk of RSV lower \nrespiratory tract disease.\nhttps://www.fda.gov/vaccines -blood -biologics/arexvy  \nhttps://www.fda.gov/vaccines -blood -biologics/abrysvo  \nhttps://www.fda.gov/vaccines -blood -biologics/vaccines/mresvia  \nEconomic analyses\nCost -effectiveness analyses : \n       Comparator       Intervention\nBase -case scenarios:  \n•What is the incremental cost-effectiveness  of vaccinating adults aged ≥75 years against RSV relative to “No \nvaccination”?\n•What is the incremental cost-effectiveness  of vaccinating adults aged 60 -74 years and 50 -59 years at increased risk \nof severe RSV disease relative to “No vaccination”?\n4Unvaccinated\nage and risk groups  \n-All ≥75yr -olds\n-Increased risk 60 -74yr -olds\n-Increased risk 50 -59yr -oldsUse of a licensed RSV vaccine \namong\n-All ≥75yr -olds\n-Increased risk 60 -74yr -olds\n-Increased risk 50 -59yr -oldsPolicy \nQuestions\n1\n2\n3\nGSK, UM-CDC and Moderna : incremental \nanalyses of vaccination strategies\nPolicy \nquestionIncremental analysis GSK modelUM-CDC model\nProtein Subunit             Moderna  \n     GSK & Pfizer                    VaccineModerna \nmodel\n1Vaccinate All ≥75yr -olds\nvs.\nNo vaccinationReviewed in \nJune 2023Included Included Included\n2Vaccinate Increased risk 60 -74yr -olds\nvs.\nNo vaccinationNot \nIncludedIncluded\n(Eight conditions)*Included\n3Vaccinate Increased risk 50 -59yr -olds\nvs.\nNo vaccinationIncluded\n(Five \nconditions) **Included***\n(Eight  \nconditions)*Not \nIncluded***Not \nIncluded***\nNo vaccination was deemed an appropriate comparator under the current shared clinical decision -making recommendation.\n* Risk conditions included chronic obstructive pulmonary disease (COPD), asthma, coronary artery disease, chronic kidney dise ase, diabetes mellitus, severe obesity (BMI ≥40), \nheart failure, and immune compromise\n** Conditions included in GSK model are COPD (base -case), heart failure, coronary artery disease, asthma, diabetes\n*** Only a single RSV vaccine (GSK AREXVY) is licensed for use in adults aged 50 -59 years who are at increased risk of RSV lower  respiratory tract disease. As such, the economic \nmodel used GSK -specific inputs for the 50 -59-year -old population. 5\n6Modeling design and assumptions\nGSK Moderna UM-CDC\nStatic analytical decision -making models \nSensitivity analyses (and probabilistic simulation)\n (\n)\n (\n)\nHypothetical populations: ≥75yrs old general population and 60 -74yrs \nold at increased risk (50 -59yrs old at increased risk)(\n)\n (\n)\nTime Frame at least 3 years after a dose of RSV vaccine*\nAnalytic Horizon: Age - and comorbidity -specific life expectancy**\nDiscount rate: 3% \nYear of economic outcomes measured: 2022/2023\nSocietal perspective (and healthcare perspective)\n (\n)\n (\n)\n (\n)\n* Base -case in UM -CDC and Moderna models relied on a two -year time frame (three -year timeframe included in scenario analysis) wh ile GSK \nused a three -year timeframe in the base -case.\nIn each model, selection of timeframe is based on the duration of protection assumption\n** Age and comorbidity specific life expectancy were used for comorbid 50 –59-year -old in  GSK model.\nGSK, Moderna  and UM-CDC models comparison: \nFrom one -way sensitivity analyses  \nWe will compare:\n•Incidence of RSV \nhospitalization and \noutpatient care\n•Medical and indirect \ncosts\n•Initial vaccine \neffectiveness \n•Vaccine waning \n•Age and risk groups\n7\nModerna : Adults ≥60yrs at high risk GSK : Adults 50 -59 yrs. at high risk Base -case= $61K/QALY saved\n8UM-CDC Moderna\nIncidence of RSV outpatient illness \n(per 100,000 persons per year)2,940 for adults ≥60 with cardiopulmonary \ndisease (including COPD)a\n1,722 for adults ≥60 with other chronic \nconditions (e.g., diabetes mellitus)b1,833  for adults 60 -64 and \n2,478 for adults ≥65 years, \ngeneral population\nIncidence of RSV hospitalization \n(per 100,000 persons per year)Age-dependent:\n198–527 for adults ≥60 with at least one \nchronic conditiond \n32–121 for adults ≥60 without chronic \nconditionsd66.5 for adults 60 -64 and \n266.7 for adults ≥65 years, \ngeneral population\nDirect medical costs per RSV \nhospitalizationAge-dependent:\n$21,417 – $22,425,e \nadjusted using median length of stay by \nchronic conditions from RSV -NET$11,876 \n($8,407 - $47,512)f,g\na Adapted from Belongia  et al. Open Forum Infect Dis (2018): https://doi.org/10.1093/ofid/ofy316 .  \nb McLaughlin et al. Open Forum Infect Dis (2022): https://doi.org/10.1093/ofid/ofac300\nc Adapted from McLaughlin et al. Open Forum Infect Dis (2022): https://doi.org/10.1093/ofid/ofac300 ; (Outpatient targets include both emergency department and outpatient visits)\nd RSV -NET, CDC unpublished data. Crude surveillance rates were adjusted using multipliers for the frequency of RSV testing durin g each season and the sensitivity of RSV diagnostic tests.  \ne Ackerson et al. J Infect Dis (2020). Updated to Q3 2022$ using GDP Deflator: https://doi.org/10.1093/infdis/jiaa183 ; Branche et al. Clin Infect Dis (2022): https://doi.org/10.1093/cid/ciab595  \nf Wyffels  V  et al (2020) A Real -World Analysis of Patient Characteristics and Predictors of Hospitalization Among US Medicare Beneficiaries with Respirat ory Syncytial Virus Infection : \nhttps://pubmed.ncbi.nlm.nih.gov/32026380/   (range values $8,407 is from Choi and $47,512 is from Pastula )\ng Merative  MarketScan  Commercial Claims and Encounters (CCAE) and Medicare Supplemental Coordination of Benefits (MDCR) Databases (2016 -2019)Moderna  and UM-CDC models:\nKey differences in model inputs, adults ≥60 years \n9UM-CDC GSK\nIncidence of RSV outpatient illness \n(per 100,000 persons per year)2,940 for adults 50 -59 with cardiopulmonary \ndisease (e.g., COPD)a\n1,722 for adults 50 -59 with other chronic \nconditions (e.g., diabetes mellitus)b2,925 \nfor adults 50 -59 with COPD a\nIncidence of RSV hospitalization \n(per 100,000 persons per year)106 for adults 50 -59 with at least one \nchronic condition c \n169 for adults 50 -59 with COPD, specifically c312\nfor adults 50 -59 with COPD d\nDirect medical costs per RSV \nhospitalization$20,330 for adults 50 -59,e \nadjusted using median length of stay, by \nchronic condition, from RSV -NET$35,308\nfor adults 50 -59f\na Adapted from Belongia  et al. Open Forum Infect Dis (2018): https://doi.org/10.1093/ofid/ofy316 . Adjusted by a factor of 1.5 for PCR sensitivity (McLaughlin et al. [2022])\nb McLaughlin et al. Open Forum Infect Dis (2022): https://doi.org/10.1093/ofid/ofac300\nc RSV-NET, CDC unpublished data. Crude surveillance rates were adjusted using multipliers for the frequency of RSV testing during each season and the sensitivity of RSV diagnostic tests.  \nd Adapted from Branche et al. (2022) across Rochester and New York City sites adjusted by a factor of 1.5 for PCR sensitivity  (McLaughlin et al. [2022])\ne Ackerson et al. J Infect Dis (2020). Updated to Q3 2022$ using GDP Deflator: https://doi.org/10.1093/infdis/jiaa183 ; Branche et al. Clin Infect Dis (2022): https://doi.org/10.1093/cid/ciab595  \nf CMS Medicare Inpatient Hospitals - by Geography and Service (CMS, 2023a); (DRG Average Payments from 2019 dataset); Falsey  et al. (2005); KFF (2020) GSK and UM-CDC models:  \nKey differences in model inputs, adults 50 -59 years \nModerna  and UM-CDC:  \nInitial or Early Peak of Vaccine Efficacy & Decline\n10a Efficacy over median 19 months (Moderna) as reported in the phase 3 clinical trials\nb Moderna phase 3 trial data; VE against medically attended acute respiratory illness\nc Moderna mRNA -1345 Efficacy from the Phase 2/3 Clinical Trial for RSV -ARD (primary analysis: 1 -4 months)\nd Moderna phase 3 trial data; VE against medically attended lower respiratory tract disease with ≥3 lower respiratory symptom s\ne Moderna mRNA -1345 Efficacy from the Phase 2/3 Clinical Trial for RSV -LRTD with ≥2 symptoms associated with shortness of breath  (primary analysis: 1 -4 months)UM-CDC Model Moderna  Model\nModerna vaccine Moderna vaccine\nVaccine efficacy against RSV outpatient  \nillnessa                                                                                         Year  154\n(0–83)bPeak: 68.4\n(50.9 –79.7)c\nYear 2Linear decline reaching zero at \nmonth 2440.1\nWeighted least square regression\nVaccine efficacy against RSV hospitalization  and \nemergency department visita                                                 Year 175\n(0–95)dPeak: 86.7\n(41.9 –97.0)e\nYear 2Linear decline reaching zero at \nmonth 2457.9\nWeighted least square regression\nModerna  and UM-CDC: Assumption on waning \nof vaccine effectiveness (VE) per outcome\n11UM-CDC ( two-year model timeframe )\nThe pink -shaded areas denote a higher level of uncertainty of the waning assumption beyond available phase 3 dataMODERNA ( two-year model timeframe ) \nARD = Acute respiratory disease\nLRTD =Lower respiratory tract disease\nEst. = estimated\nED = Emergency department0%10%20%30%40%50%60%70%80%90%100%\n0 2 4 6 810 12 14 16 18 20 22 24 26 28 30 32 34 36Efficacy\nMonth\nMedically attended RSV ARD (outpatient)\nEst. Medically attended RSV ARD (outpatient)\nMedically attended RSV LRTI/LRTD with 3+ symptoms (ED, hospitalization)\nEst. Medically attended RSV LRTI/LRTD with 3+ symptoms (ED, hospitalization)Linear decay to 0% \nby 24 months75%\n54%\n(Outpatient and ED)\n(Outpatient and ED)\n(Hospitalization)\n(Hospitalization)\nGSK and UM-CDC:  \nInitial or Early Peak of Vaccine Efficacy & Decline\n12a Efficacy over median 23 months follow up (GSK) as reported in the phase 3 clinical trials\nb GSK phase 3 trial data; VE against medically attended acute respiratory illness\nc GSK phase 3 trial data; VE against acute respiratory illness, regardless of whether medically attended. During month 1, 50%  of peak VE is assumed, with linear waning in months 2+ based on \nweighted linear regression.\nd Observational vaccine effectiveness, GSK -specific. \ne Proportional waning applied to Season 1 efficacy, from GSK phase 3 trial efficacy against lower respiratory tract disease ( Season 2 vs. Season 1)\nf GSK phase 3 trial data; VE against lower respiratory tract disease, regardless of whether medically attended. During month 1, 50% of peak VE is assumed, with linear waning in months 2+ based \non weighted linear regression.UM-CDC Model GSK Model\nGSK vaccine GSK vaccine\nVaccine efficacy against RSV outpatient  \nillnessa                                                                              Year  179\n(54–92)bPeak: 73.3\n(57.9 –87.4)c\nYear 2+28\n(0–60)bWeighted linear regression over time \n(-2.1% monthly waning)c\nVaccine efficacy against RSV hospitalization  and \nemergency department visita                                                Year 184\n(74–90)dPeak: 86.5\n(67.7 –98.7)f\nYear 2+60\n(43–72)eWeighted linear regression over time \n(-1.8% monthly waning)f\nGSK: Residual Vaccine Effectiveness (VE) analyses \n(3-year timeframe )\n13RSV LRTD : 50% of peak VE ( 86.5% ) \nassumed in month 1, peak VE \ndeclines by 1.8%  monthly rate \nbeginning in month 2 though 23 -\nmonth follow up of trial.  Assumed \nto follow linear decline trend \nafterwards. Reaches 0% near month \n48\nRSV ARI : 50% of peak VE ( 73.3% ) \nassumed in month 1, peak VE \ndeclines by 2.1%  monthly rate \nbeginning in month 2 though 23 -\nmonth follow up of trial.  Assumed \nto follow linear decline trend \nafterwards. Reaches 0% in month 36\nSource : GSK Technical report and Slides June \n2024\nLRTD= Lower respiratory tract disease\nARI= Acute respiratory illness\nLB= Lower bound\nThe pink -shaded area denotes a higher level of uncertainty of the waning assumption beyond \navailable phase 3 data\n79%\n28%78%\n55%84%\n60%\n0%10%20%30%40%50%60%70%80%90%100%\n0 6 12 18 24 30GSK vaccine efficacy\nMonths since vaccination\n14UM-CDC: Assumption of waning of vaccine \nefficacy ( GSK vaccine) ( 2-year timeframe )\nThe pink -shaded area denotes a higher level of uncertainty of the waning assumption beyond available phase 3 data____  \nHospitalization \n(including ICU \n& death)\n____  \nEmergency \nDepartment \nvisit\n____  \nOutpatient \nvisit\n* Target population: All adults ≥75yrs (Table 27, Moderna Technical report June13,2024)  \n** Target population: High -risk 60 -74yrs (Table 27, Moderna Technical report June13,2024)  Policy questions 1 & 2:  Moderna  and UM-CDC\nModerna model\nModerna vaccineUM-CDC model\nModerna vaccine\n$/QALY saved (2-year \ntimeframe )$55,995* $66,287\n$/QALY saved ( 3-year \ntimeframe )Not reported $42,495Policy question 1 . What is the incremental cost-effectiveness  of vaccinating alladults aged ≥75 \nyears old against RSV illness relative  to “No vaccination”? \n15Policy question 2 : What is the incremental cost-effectiveness  of vaccinating adults aged 60 -74 years old at \nincreased risk of severe RSV illness relative  to “No vaccination”? \n$/QALY saved ( 2-year \ntimeframe )$89,064** $80,953\n$/QALY saved ( 3-year \ntimeframe )Not reported $49,198\n* GSK estimated cost -saving values for four high risk conditions: COPD, heart failure, CAD and Diabetes. For Asthma, GSK estimat ed societal cost of $2,445/ QALY saved\n** In the base case (2 -year vaccine effectiveness timeframe), Michigan estimated a societal cost of $154,501 /QALY saved for adults with at least one chronic condition \n(COPD, asthma, CAD, CKD, Severe Obesity, or Diabetes). For individual conditions, societal costs ranged from $30,720 (CKD) to $171,661 (Diabetes) per QALY sav ed. \nWhen evaluating other specific conditions not included in “at least one” , $/QALY ranged from cost -saving (lung transplant, allogeneic hematopoietic cell transplant) to \n$14,335 (heart failure) and $14,521 (autologous hematopoietic cell transplant).Policy question 3:  GSK and UM-CDC\nPolicy question 3:  What is the incremental cost-effectiveness  of vaccinating adults aged 50 -59 \nyears at increased risk of severe RSV illness relative  to “No vaccination”? \n16GSK* UM-CDC**\n$/QALY saved ( 2-year \ntimeframe )Not reported $154,501\n$/QALY saved ( 3-year \ntimeframe )Cost -saving to $2,445 $112,949\nLimitations\n17•Factors not considered that may result in underestimating the cost -effectiveness of RSV \nvaccination\n•No impact of RSV on long -term prognosis of COPD or of other higher risk conditions \n•No indirect effects of vaccination (i.e., no protection against RSV transmission)\n•No productivity or quality of life impact on caregivers during RSV illness\n•All models partially  include RSV-related medical costs incurred after discharge from an RSV -associated \nhospitalization or emergency department visit: Stay in long -term care or rehabilitation facility\n•Manufacturer models partially  include potential  vaccine -associated serious adverse events (SAEs) \nor from Guillain Barre syndrome (GBS): Quality of life impact, resource utilization, and costs \nassociated with SAEs, including GBS specifically for protein subunit RSV vaccines.\n•Vaccine efficacy beyond median clinical trial follow -up time (beyond 19 months, Moderna ; or 23 \nmonths, GSK) is unknown  \n•All 3 models assumed non -zero declining  efficacy beyond trial time data\n•All 3 models assumed seasonal vaccination (with optimal timing in the late summer and early fall) \nwithout off -RSV-season vaccination impact.\nConclusion\n18•Differences in key inputs and assumptions among GSK, Moderna  and UM-CDC models explain \ndifferences in results:\n•Annual incidence of RSV hospitalization and outpatient disease\n•Initial vaccine effectiveness and waning of protection\n•Medical cost per RSV hospitalization \nResulting ICERs for policy questions vary by age and high -risk group:\n•1: Vaccinating all adults aged ≥75 years old against RSV illness\n•Moderna  and UM-CDC models reported societal costs between $51K to $66K per QALY saved \n•2: Vaccinating adults aged 60 -74 years old at higher risk of severe RSV disease\n•Moderna  and UM-CDC models reported societal costs between $61K to $89K per QALY saved\n•3: Vaccinating adults aged 50 -59 years old at higher risk showed more discrepant $/QALY ratios\n•Outcomes ranged from societal cost-saving  (GSK) to $154K per QALY saved ( UM-CDC) \nOverall, vaccination would significantly reduce RSV disease burden in adults 50 -59 and 60 -74 years \nold at higher risk of RSV disease and in the general population of adults aged ≥75 years old.\n•Efficacy clinical trial data and assumptions support impact on disease reduction\nAcknowledgements \nFrom NCIRD/CORVD\n•Michael Melgar\n•Amadea Britton\n•Katherine Fleming -Dutra\nAlso:\n•Adult RSV working group members\n•Andrew Leidner and the Econ team from NCRID/ISD\n19\n\nEnd of Summary", "summary": "Economics of Respiratory Syncytial Virus (RSV)  Vaccination in All U.S. Adults≥75 years -old, and  Adults aged 60 -74 and 50-59 years  at Increased Risk SUMMARY COMPARING MODELS FROM: GSK,Moderna AND University of Michigan -CDC Ismael R. Ortega -Sanchez, PhD NCIRD/CDC ACIP Meeting, June 26, 2024 1Disclaimer : The findings and conclusions in this report are those of the authors and do not necessarily represent the views of  the Centers for Disease Control and Prevention.  National Center for…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/10-RSV-Adult-Ortega-Sanchez-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 20}
{"title": "11 RSV Adult Melgar Roper Britton 508", "content": "1\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nEvidence to Recommendations Framework (EtR):\nRSV Vaccination in Adults Aged 50 –59 years, 60 –74 years, \nand 75 years and older\nAmadea Britton, MD, Co -Lead Adult RSV Vaccine Work Group\nMichael Melgar, MD, Co -Lead Adult RSV Vaccine Work Group\nLauren Roper, MPH\nCoronavirus and Other Respiratory Viruses Division (CORVD)\nAdvisory Committee on Immunization Practices (ACIP)\nJune 26, 2024\n2▪Should alladults aged ≥75 years be recommended to receive a single dose \nof RSV vaccination?\n▪Should adults aged 60–74years at increased risk of severe RSV disease be \nrecommended to receive a single dose of RSV vaccination?\n▪Should adults aged 50–59years at increased risk of severe RSV disease be \nrecommended to receive a single dose of RSV vaccination?Policy questions\n3We will consider the first two questions together in EtR and \nthen return to the 50 –59 age group. \n4Evidence to Recommendations ( EtR ) framework\nACIP Evidence to Recommendations Framework (cdc.gov)EtR Domain Question(s)\nPublic Health Problem ▪Is the problem of public health importance?\nBenefits and Harms ▪How substantial are the desirable anticipated effects?\n▪How substantial are the undesirable anticipated effects?\n▪Do the desirable effects outweigh the undesirable effects?\nValues ▪Does the target population feel the desirable effects are large relative \nto the undesirable effects?\n▪Is there important uncertainty about, or variability in, how much \npeople value the main outcomes?\nAcceptability ▪Is the intervention acceptable to key stakeholders?\nFeasibility ▪Is the intervention feasible to implement?\nResource Use ▪Is the intervention a reasonable and efficient allocation of resources?\nEquity ▪What would be the impact of the intervention on health equity?\n5\nEtR Domain: Public Health Problem\nIs the problem of public health importance among adults aged ≥75 years?\nIs the problem of public health importance among adults aged 60 –74 \nyears at increased risk of severe RSV disease?\n6RSV was associated with1\n90,000 –140,000 annual\nhospitalizations in \nU.S. adults aged 65 years and older\nand\n10,000 –20,000 annual\nhospitalizations in \nU.S. adults aged 60–64 yearsInfluenza* was associated with2\n170,000 –470,000 annual\nhospitalizations in \nU.S. adults aged 65 years and olderDuring 2016 –2020, CDC estimates:\n1. Preliminary CDC RSV -NET data 2016 –2020 (unpublished). Updated from prior CDC estimates \nwhich are available at: https://www.cdc.gov/rsv/php/surveillance/index.html  \nRanges reflect point estimates for individual seasons, but not uncertainty in those estimates2. CDC Influenza Burden 2016 –2020: https://www.cdc.gov/flu/about/burden/past -seasons.html  *Annual influenza disease burden is attenuated \nby the routine vaccination program. \n70200400600800\n18–49 50–54 55–59 60–64 65–69 70–74 75–79 ≥80 Annual RSV -associated hospitalizations \nper 100,000 population \nAge group, years2016 –17\n2017 –18\n2018 –19\n2019 –20\nUnpublished data. Rates are adjusted using multipliers for the frequency of RSV testing during each season and the sensitivit y of RSV diagnostic tests. Error bars represent 95% \nconfidence intervals.\n*Estimated rates exclude recorded hospitalizations among pregnant adults.\nhttps://www.cdc.gov/rsv/research/rsv -net/index.html  Estimated annual RSV -associated hospitalization  rates per 100,000 adults* \n≥18 years by age group and year, RSV -NET, 2016 –17 to 2019 –20\nSurveillance \nseason:\n8Adjusted Rate Ratios for RSV -Associated Hospitalization by Chronic \nCondition among Community -Dwelling Adults Aged ≥50 Years\n6.5\n4.63.7\n3.12.4\n2.0 1.91.5 1.3\n0.11.010.0100.0\nChronic\nKidney\nDiseaseCOPD Severe \nobesity\n(BMI ≥40)Asthma Coronary\nArtery\nDiseaseDiabetes\nmellitusCurrent\nsmokerStroke Obesity\n(BMI 30-39)aRR\nUnpublished data. Update on analysis from Woodruff et al. First presented to ACIP in February 2024: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2024 -02-28-29/03 -RSV-Adults -Woodruff -508.pdf  \nBMI: Body Mass Index (kg/m2), COPD: Chronic Obstructive Pulmonary Disease, aRR: adjusted rate ratio. Data are preliminary and unpublished. Adjusted rate ratios and 95% confidence intervals are derived fr om Poisson \nregression using Monte Carlo simulation methods and adjust for age, sex and race and ethnicity group. Error bars represent 95 % confidence intervals.\n9aRR (95% CI)1\nNo. of chronic conditions2\n0 ref\n1 2.1 (1.4, 3.2)\n≥2 7.3 (5.0, 10.6)\nAge group, years\n50–59 ref\n60–74 1.9 (1.3, 2.7)\n≥75 6.0 (4.2, 8.6)\nRace or ethnicity group\nWhite, non -Hispanic ref\nBlack, non -Hispanic 1.1 (0.8, 1.5)\nOther race or Hispanic ethnicity 1.7 (1.3, 2.5)\nSex\nMale Ref\nFemale 1.3 (1.0, 1.6)\n1 Adjusted rate ratios ( aRR) and 95% confidence intervals (CI) were estimated using \nPoisson regression using Monte Carlo simulation.\n2 Includes history of asthma, chronic kidney disease, chronic obstructive pulmonary \ndisease, coronary artery disease, current smoker, diabetes, stroke, obesity (BMI 30 –39) \nor severe obesity (BMI ≥40)Among community -dwelling \nadults aged ≥50 years, a \nhistory of ≥2 chronic \nconditions  and age ≥75 \nyears were the strongest \nindependent  risk factors for \nRSV-associated \nhospitalization.\nUnpublished data. Update on analysis from Woodruff et al. First presented to ACIP in February 2024: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2024 -02-28-29/03 -RSV-Adults -Woodruff -508.pdf  \n10▪Other medical conditions associated with increased risk of severe RSV disease\n–Heart failure\n•As many as 28% of adults hospitalized with RSV infection have chronic heart failure1\n•Among  adults 65 years and older, hospitalization rates are 3.5x higher in those with versus \nwithout heart failure1\n–Immune compromise\n•Severe disease and high mortality (>20%), especially among lung transplant and \nhematopoietic cell transplant recipients2,3\n▪Persons living in long -term care facilities are also at increased risk of RSV hospitalization and \nsevere outcomes4,5\n–Frequent cause of respiratory illness and outbreaks What do we know about conditions and risk factors not \nincluded in the RSV -NET analysis?\n1.Kujawski  SA, et al. (2022) Rates of respiratory syncytial virus (RSV) -associated hospitalization among adults with congestive heart fail ure—United States, 2015 –2017. PLOS ONE 17(3): \ne0264890. https://doi.org/10.1371/journal.pone.0264890    \n2.Ison MG, Hirsch HH. Community -Acquired Respiratory Viruses in Transplant Patients: Diversity, Impact, Unmet Clinical Needs. Clin  Microbiol  Rev. 2019 Sep 11;32(4):e00042 -19. \nhttps://pubmed.ncbi.nlm.nih.gov/31511250/  \n3.Manuel O, Estabrook M; American Society of Transplantation Infectious Diseases Community of Practice. RNA respiratory viral i nfections in solid organ transplant recipients: Guidelines \nfrom the American Society of Transplantation Infectious Diseases Community of Practice. Clin Transplant. 2019 Sep;33(9):e1351 1 https://pubmed.ncbi.nlm.nih.gov/30817023/  \n4.Bosco E, et al. Estimated Cardiorespiratory Hospitalizations Attributable to Influenza and Respiratory Syncytial Virus Among Lon g-term Care Facility Residents. JAMA Netw  Open. 2021 Jun \n1;4(6):e2111806. https://pubmed.ncbi.nlm.nih.gov/34106266/  \n5.Childs A, et al. The burden of respiratory infections among older adults in long -term care: a systematic review. BMC Geriatr . 2019 Aug 5;19(1):210 https://pubmed.ncbi.nlm.nih.gov/31382895/  \n11▪Among unvaccinated adults, disease severity of RSV -associated \nhospitalization is similar to severity of COVID -19- and influenza -\nassociated hospitalization .1\n▪High incidence of acute cardiac events among adults 50 and older \nhospitalized with RSV infection, including 1 in 12 adults (8.5%) with no \ndocumented underlying cardiovascular disease.2\n▪Patients hospitalized for RSV -associated disease often require follow‐up \ncare and skilled nursing after discharge.3Other considerations: RSV disease severity and \ncomplications among adults not vaccinated against RSV\n1. Surie D, Yuengling KA, DeCuir J, et al. Severity of Respiratory Syncytial Virus vs COVID -19 and Influenza Among Hospitalized US Adults. JAMA Netw  Open. 2024 Apr 1;7(4):e244954. https://pubmed.ncbi.nlm.nih.gov/38573635/  \n2. Woodruff RC, Melgar M, Pham H, et al. Acute Cardiac Events in Hospitalized Older Adults With Respiratory Syncytial Virus Infecti on. JAMA Intern Med. 2024;184(6):602 –611. doi:10.1001/jamainternmed.2024.0212\n3. Walsh E, Lee N, Sander I, Stolper  R, Zakar  J, Wyffels  V, Myers D, Fleischhackl  R. RSV -associated hospitalization in adults in the USA: A retrospective chart review investigating burden, management strategie s, and outcomes. Health \nSci Rep. 2022 Apr 14;5(3):e556. doi: 10.1002/hsr2.556. PMID: 35509398; PMCID: PMC9059216.\n12▪Annual rate of RSV -associated hospitalization increases with increasing \nage , with a steep rise at age 75 years. \n▪Certain chronic medical conditions also increase risk of RSV -associated \ndisease. Age  and chronic medical conditions are independently  associated \nwith increased risk. \n▪RSV is associated with severe disease and has significant post -\nhospitalization sequelae among older adults.Public health problem: summary of the available evidence\nAdults 60 years and older\n13▪Is RSV of public health importance among adults aged  ≥75 years ?\n▪Is RSV of public health importance among adults aged  60–74 \nyears at increased risk of severe RSV disease ? Public Health Problem: Work Group interpretation\nNoProbably \nNoProbably \nYesYes VariesDon’t \nknow\nNoProbably \nNoProbably \nYesYes VariesDon’t \nknow\n14\nEtR  Domain: Benefits and Harms\n- How substantial are the desirable anticipated effects?\n- How substantial are the undesirable anticipated effects?\n- Do the desirable effects outweigh the undesirable effects?\n15▪Protein subunit RSV vaccines (Pfizer ABRYSVO, GSK AREXVY)\n–Adults 75 years and older\n•GRADE\n•Additional considerations\n–Adults aged 60 –74 years at increased risk of severe RSV disease\n•GRADE\n•Additional considerations\n▪mRNA RSV vaccine (Moderna mRESVIA )\n–Repeat as aboveBenefits and Harms overview\n16GRADE Framework: PICO Question\nPopulation Adults aged ≥75 years\nIntervention Protein Subunit RSV Vaccine:\nPfizer ABRYSVO (1 dose IM) -or-GSK AREXVY (1 dose IM)\nComparison No RSV vaccine\nOutcomes ▪RSV lower respiratory tract disease (LRTD)\n▪Medically attended RSV LRTD\n▪Hospitalization for RSV respiratory illness\n▪Severe RSV respiratory illness requiring supplemental oxygen or \nother respiratory support\n▪Death due to RSV respiratory illness\n▪Serious Adverse Events (SAEs)\n▪Inflammatory neurologic events (e.g., Guillain -Barré syndrome)\n▪Reactogenicity (grade ≥3)\n17Summary of GRADE for protein subunit RSV vaccines in adults ≥75 years\nOutcome​ ImportanceDesign\n(# of studies)​Findings​Evidence\ntype​\nBenefits\nRSV Lower Respiratory Tract \nDisease (LTRD)Important RCT (2)Protein subunit RSV vaccination reduces RSV LRTD in adults aged ≥75 \nyears.High\nMedically attended RSV LRTD Critical RCT (2)Protein subunit RSV vaccination likely reduces medically attended RSV \nLRTD in adults aged ≥75 years.Moderate\nHospitalization for RSV \nrespiratory illnessCritical RCT (2)Protein subunit RSV vaccination may reduce hospitalization for RSV \nrespiratory illness in adults aged ≥75 years .Low\nSevere RSV respiratory illness \nrequiring O2/respiratory \nsupportImportant RCT (2)Protein subunit RSV vaccination may reduce severe RSV respiratory \nillness requiring supplemental oxygen or other respiratory support in \nadults aged ≥75 years , but the effect is very uncertain.Very low\nDeath due to RSV respiratory \nillnessImportant RCT (2) Zero events observed Unable to \nevaluate\nHarms\nSerious adverse events​ (SAEs) Critical RCT (4)Protein subunit RSV vaccination likely results in little to no difference in \nSAEs in adults aged ≥75 years.Moderate\nInflammatory neurologic events Critical RCT (4)Protein subunit RSV vaccination may increase inflammatory neurologic \nevents in adults aged ≥75 years, but the effect is very uncertain.Very low\nReactogenicity ​(grade ≥3) Important RCT (4)Protein subunit RSV vaccination may increase severe reactogenicity \nevents in adults aged ≥75 years.Low\n18Summary of GRADE for protein subunit RSV vaccines in adults ≥75 years\nOutcome​ ImportanceDesign\n(# of studies)​Findings​Evidence\ntype​\nBenefits\nRSV Lower Respiratory Tract \nDisease (LTRD)Important RCT (2)Protein subunit RSV vaccination reduces RSV LRTD in adults aged ≥75 \nyears.High\nMedically attended RSV LRTD Critical RCT (2)Protein subunit RSV vaccination likely reduces medically attended RSV \nLRTD in adults aged ≥75 years.Moderate\nHospitalization for RSV \nrespiratory illnessCritical RCT (2)Protein subunit RSV vaccination may reduce hospitalization for RSV \nrespiratory illness in adults aged ≥75 years .Low\nSevere RSV respiratory illness \nrequiring O2/respiratory \nsupportImportant RCT (2)Protein subunit RSV vaccination may reduce severe RSV respiratory \nillness requiring supplemental oxygen or other respiratory support in \nadults aged ≥75 years , but the effect is very uncertain.Very low\nDeath due to RSV respiratory \nillnessImportant RCT (2) Zero events observed Unable to \nevaluate\nHarms\nSerious adverse events​ (SAEs) Critical RCT (4)Protein subunit RSV vaccination likely results in little to no difference in \nSAEs in adults aged ≥75 years.Moderate\nInflammatory neurologic events Critical RCT (4)Protein subunit RSV vaccination may increase inflammatory neurologic \nevents in adults aged ≥75 years, but the effect is very uncertain.Very low\nReactogenicity ​(grade ≥3) Important RCT (4)Protein subunit RSV vaccination may increase severe reactogenicity \nevents in adults aged ≥75 years.Low\n19Additional information on benefits/harms for protein \nsubunit RSV vaccines in adults aged ≥75 years\n20Per 1 Million Vaccine Doses Administered to Adults Aged ≥75 Years :\n1.Range of outcomes avertable was calculated using published 95% confidence intervals (outpatient only) and adjusted 95% confid ence interval of RSV -associated incidence of the outcome observed in RSV -NET\n2. FDA self -controlled case series analysis, among CMS Medicare beneficiaries ≥65 years with Parts A, B, and D coverage who did not  have a GBS claim in the 365 days before vaccination. Analysis based on \ndiagnoses of GBS in inpatient claims data in risk interval (1 –42 days after RSV vaccination) compared to control interval (43 –90 days after RSV vaccination). GBS cases identified using ICD -10 diagnosis of \nGBS in primary position of inpatient claims coding. Estimates adjusted for outcome -dependent observation time, positive predicti ve value of diagnostic codes in identifying chart -confirmed GBS cases, and \nseasonality. Analysis includes patients with RSV vaccinations only through October 8, 2023 to allow for 90 -day post -vaccination observation and 90% or greater claims data completeness. Claims data \nthrough April 6, 2024. \n3. Self -controlled case series analysis estimated attributable risk of 3 (95% CI: -3, 10) GBS cases. However, the range was truncat ed at zero for Benefit/Risk analyses.Estimated RSV -Associated Outcomes1 Preventable over 2 RSV Seasons  vs. potential cases of GBS\n(positive predictive value -adjusted  attributable risk of GBS in FDA -CMS partnership data among adults \naged ≥65 years, 42 -day risk interval2)\n3 (range  0–10)3 attributable  cases of GBS 16 (range 3–29) attributable cases of GBS610 630 4,300 \n -  1,000  2,000  3,000  4,000  5,000  6,000  7,000540 560 3,800 \n -  1,000  2,000  3,000  4,000  5,000  6,000  7,000Hospitalizations\nICU Admissions\nDeathsAREXVY (GSK) ABRYSVO (Pfizer)\n(2,200 –7,000)\n(330 –1,000)\n(200 –1,300)(1,900 –6,300)\n(280 –920)\n(190 –1,100)\n21▪Vaccine Safety Datalink (VSD) rapid cycle analysis signal for immune thrombocytopenic purpura (ITP)1\n–VSD identified a statistical signal for ITP in adults ≥60 years who received GSK (AREXVY) RSV \nvaccination\n•Too early to determine if this represents a true association. After rapid medical record review, most \nwere found not to be new cases of ITP occurring after RSV vaccination . \n▪Co-administration with other vaccines\n–Publicly available data on coadministration of GSK AREXVY or Pfizer ABRYSVO with other adult \nvaccines remain limited.2,3\n–Especially important consideration in older adults recommended to receive multiple vaccines (e.g., \nCOVID -19, influenza, pneumococcal, recombinant zoster)Other benefit and harms considerations:\nProtein subunit RSV vaccines\nAbbreviations: VSD: Vaccine Safety Datalink\n1. Donahue J. Presentation at June 2024 ACIP meeting.\n2.https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2023 -06-21-23/03 -RSV -Adults -Friedland -508.pdf\n3.https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2023 -06-21-23/02 -RSV -Adults -Gurtman -508.pdf   \n22▪How substantial are the desirable anticipated effects among adults aged ≥75 years?\n▪How substantial are the undesirable anticipated effects among adults aged ≥75 years?\n▪Do the desirable effects outweigh the undesirable effects among adults aged ≥75 years?Benefits and Harms: Protein Subunit RSV vaccine in adults aged ≥75 \nyears\nMinimal Small Moderate Large Varies Don’t know\nMinimal Small Moderate Large Varies Don’t know\nFavors intervention ( Protein subunit RSV vaccine)\nFavors comparison (no vaccine)\nFavors both\nFavors neither\nUnclear\n23GRADE Framework: PICO Question\nPopulation Adults aged 60 –74 years at increased risk of severe RSV disease\nIntervention RSV Protein Subunit Vaccine:\nPfizer ABRYSVO (1 dose IM) -or-GSK AREXVY (1 dose IM)\nComparison No RSV vaccine\nOutcomes ▪RSV lower respiratory tract disease (LRTD)\n▪Medically attended RSV LRTD\n▪Hospitalization for RSV respiratory illness\n▪Severe RSV respiratory illness requiring supplemental oxygen or \nother respiratory support\n▪Death due to RSV respiratory illness\n▪Serious Adverse Events (SAEs)\n▪Inflammatory neurologic events (e.g., Guillain -Barré syndrome)\n▪Reactogenicity (grade ≥3)\n24Summary of GRADE for protein subunit vaccines in adults aged 60 –74 years at \nincreased risk  of severe RSV disease\nOutcome ImportanceDesign\n(# of studies)Findings\nIn adults aged 60 -74 years at increased risk of severe RSV disease:Evidence\ntype\nBenefits\nRSV Lower Respiratory \nTract Disease (L TRD)Important RCT (2) Protein subunit RSV vaccination reduces RSV LRTD. High\nMedically attended RSV \nLRTDCritical RCT (2) Protein subunit RSV vaccination reduces medically attended RSV LRTD. High\nHospitalization for RSV \nrespiratory illnessCritical RCT (2)Protein subunit RSV vaccination may reduce hospitalization for RSV respiratory \nillness.Low\nSevere RSV respiratory \nillness requiring \nO2/respiratory supportImportant RCT (2)Protein subunit RSV vaccination may reduce severe RSV respiratory illness \nrequiring supplemental oxygen or other respiratory support, but the effect is very \nuncertain.Very low\nDeath due to RSV \nrespiratory illnessImportant RCT (2) Zero events observedUnable to \nevaluate\nHarms\nSerious adverse events Critical RCT (4) Protein subunit RSV vaccination likely results in little to no difference in SAEs. Moderate\nInflammatory neurologic \neventsCritical RCT (4)Protein subunit RSV vaccination may increase inflammatory neurologic events, \nbut the effect is very uncertain.Very low\nReactogenicity (grade ≥3) Important RCT (4) Protein subunit RSV vaccination may increase severe reactogenicity events. Low\n25Additional information on benefits/harms for protein \nsubunit vaccines in adults aged 60 –74 years at increased \nrisk of severe RSV disease\n26Per 1 Million Vaccine Doses Administered to Adults Aged 60 –74 Years at \nIncreased Risk of Severe RSV Disease :\n1.Range of outcomes avertable was calculated using published 95% confidence intervals (outpatient only) and adjusted 95% confid ence interval of RSV -associated incidence of the outcome observed in RSV -NET\n2. FDA self -controlled case series analysis, among CMS Medicare beneficiaries ≥65 years with Parts A, B, and D coverage who did not  have a GBS claim in the 365 days before vaccination. Analysis based on \ndiagnoses of GBS in inpatient claims data in risk interval (1 -42 days after RSV vaccination) compared to control interval (43 -90 days after RSV vaccination). GBS cases identified using ICD -10 diagnosis of \nGBS in primary position of inpatient claims coding. Estimates adjusted for outcome -dependent observation time, positive predicti ve value of diagnostic codes in identifying chart -confirmed GBS cases, and \nseasonality. Analysis includes patients with RSV vaccinations  only through October 8, 2023 to allow for 90 -day post -vaccination  observation and 90% or greater claims data completeness. Claims data \nthrough April 6, 2024. \n3. Although CMS data were limited to Medicare beneficiaries aged ≥65 years, results are extrapolated here to include adults aged  60-64 years.\n4. Self -controlled case series analysis estimated attributable risk of 3 (95% CI: -3, 10) GBS cases. However, the range was truncat ed at zero for Benefit/Risk analyses.Estimated RSV -Associated Outcomes1 Preventable over 2 RSV Seasons  vs. potential cases of GBS\n(positive predictive value -adjusted  attributable risk of GBS in FDA -CMS partnership data among adults \naged ≥65 years, 42 -day risk interval2,3)\n250 650 2,800 \n -  1,000  2,000  3,000  4,000  5,000  6,000  7,000220 580 2,500 \n -  1,000  2,000  3,000  4,000  5,000  6,000  7,000Hospitalizations\nICU Admissions\nDeathsAREXVY (GSK) ABRYSVO (Pfizer)\n3 (range 0–10)4 attributable  cases of GBS 16 (range 3–29) attributable cases of GBS(1,500 –4,700)\n(340 –1,070)\n(80–440)(1,400 –4,200)\n(310 –960)\n(70–400)\n27Vaccine Primary outcomeEfficacy (95% CI), \nmonths 0 –12aEfficacy (95% CI),\nmonths 13 –24a\nPfizer ABRYSVORSV LRTI with ≥2 lower \nrespiratory sx62%  (41, 76)\nMedian 12 months follow -up per \nparticipant55%  (26, 73)\nMedian 6 months follow -up per \nparticipant\nRSV LRTI with ≥3 lower \nrespiratory sx86%  (63, 96)\nMedian 12 months follow -up per \nparticipant74%  (27, 92)\nMedian 6 months follow -up per \nparticipantProtein subunit RSV vaccine efficacy against primary \nclinical trial outcomes over time\nAbbreviations: CI: confidence interval, LRTI: lower respiratory tract illness, sx: signs or symptoms, LRTD: lower respiratory tract disease\na.Nominal efficacy during 12 -month period. Not all trial participants contributing to estimate had full 12 months’ follow up time during \nthe period. Median per -participant follow -up time during each period is reported below each estimate.\nPfizer and GSK clinical trials used different primary endpoint definitions and had different follow -up time, so efficacy cannot be \ndirectly compared across trials. \n28Vaccine Primary outcomeEfficacy (95% CI), \nmonths 0 –12aEfficacy (95% CI),\nmonths 13 –24a\n \n \n \nGSK AREXVYRSV LRTD (≥2 or ≥3 \nlower respiratory sx)b79%  (58, 90)\nMedian 12 months follow -up per \nparticipant59%  (34, 75)\nMedian 12 months follow -up per \nparticipantProtein subunit RSV vaccine efficacy against primary \nclinical trial outcomes over time\nAbbreviations: CI: confidence interval, LRTI: lower respiratory tract illness, sx: signs or symptoms, LRTD: lower respiratory tract disease\na.Nominal efficacy during 12 -month period. Not all trial participants contributing to estimate had full 12 months’ follow up time during \nthe period. Median per -participant follow -up time during each period is reported below each estimate.\nb.GSK definition of LRTD required ≥2 lower respiratory symptoms or signs (including ≥1 sign), or ≥3 lower respiratory symptoms.\nPfizer and GSK clinical trials used different primary endpoint definitions and had different follow -up time, so efficacy cannot be \ndirectly compared across trials. \n29Revaccination with GSK AREXVY at 12 months does not \nincrease efficacy, compared with a single dose\n\n30▪How substantial are the desirable anticipated effects among adults aged 60 –74 years at increased risk \nof severe RSV disease\n▪How substantial are the undesirable anticipated effects among adults aged 60 –74 years at increased \nrisk of severe RSV disease?\n▪Do the desirable effects outweigh the undesirable effects among adults aged 60 –74 years at increased \nrisk of severe RSV disease?Benefits and Harms Protein Subunit RSV vaccine in adults aged 60 –74 \nyears at increased risk of severe RSV disease\nMinimal Small Moderate Large Varies Don’t know\nMinimal Small Moderate Large Varies Don’t know\nFavors intervention ( Protein subunit RSV vaccine)\nFavors comparison (no vaccine)\nFavors both\nFavors neither\nUnclear\n31GRADE Framework: PICO Question\nPopulation Adults aged ≥75 years\nIntervention RSV Vaccine:\nModerna mRESVIA (50μg,single dose IM)\nComparison No RSV vaccine\nOutcomes ▪RSV lower respiratory tract disease (LRTD)\n▪Medically attended RSV LRTD\n▪Hospitalization for RSV respiratory illness\n▪Severe RSV respiratory illness requiring supplemental oxygen or \nother respiratory support\n▪Death due to RSV respiratory illness\n▪Serious Adverse Events (SAEs)\n▪Inflammatory neurologic events (e.g., Guillain -Barré syndrome)\n▪Reactogenicity (grade ≥3)\n32Outcome Importance Data SourcesEffect Estimate, Vaccine \nEfficacy (95% CI)aConcerns in certainty \nassessment\nRSV Lower Respiratory Tract \nDisease (L TRD)b,c Important\nOne Phase 2/3 RCT in \nadults ≥60 years1\n• Mean efficacy follow \nup through 18 months \npost -vaccination per \nparticipant (median 19 \nmonths)d44.0% ( -34.6, 78.2%) Imprecision (serious)e\nMedically attended RSV LRTDf,cCritical 39.0% ( -58.8, 78.1%)Indirectness (serious)g\nImprecision (serious)e\nHospitalization for RSV \nrespiratory illnessf Critical 80.1% ( -363.7, 100%)h Indirectness (serious)f\nImprecision (very serious)i\nSevere RSV respiratory illness \nrequiring O2/respiratory supportImportant No data available Unable to evaluate\nDeath due to RSV respiratory \nillnessd Important Zero events observed Unable to evaluateModerna mRESVIA  in adults aged ≥75 years\nBenefits: vaccine efficacy estimates\na) Calculated as (1 –  Incident Rate Ratio) x 100%. Events were included if they occurred >14 days post -vaccination.\nb) Included data are from participants aged ≥75 years. \nc) LRTD using co -primary endpoint of at LRTD with at least 3 signs or symptoms\nd) Efficacy follow -up through maximum 24 months postvaccination per participants (median 19 months)\ne) Serious concern for imprecision due to the confidence intervals containing absolute risk reduction estimates for which differ ent policy decisions might be considered.\nf) Included data are among all Moderna RCT participants (aged ≥60 years).\ng) Serious concern for indirectness due to inclusion of adults aged 60 –74 years.\nh) Calculated using 0.5 correction factor to account for zero events in the placebo group. Data cut off April 2023.\ni) Serious concern for imprecision due to the confidence intervals containing absolute risk reduction estimates for which differ ent policy decisions might be considered and fragility of the estimate\n1. Clinical trials.gov NTC:05127434. https://classic.clinicaltrials.gov/ct2/show/NCT05127434 . Wilson E, Goswami J, Baqui  AH, et al. Efficacy and Safety of an mRNA -Based RSV PreF  Vaccine in Older \nAdults. N Engl J Med. 2023 Dec 14;389(24):2233 -2244. doi: 10.1056/NEJMoa2307079. Plus additional data obtained directly from the manufacturer\n33Outcome Importance Data SourcesEffect Estimate, Risk ratio \n(95% CI)Concerns in certainty \nassessment\nSerious adverse events \n(SAEs)a,b CriticalOne phase 2/3 RCT1,\none phase 1 RCT2 1.00 (0.95, 1.05)Inconsistency (serious)c\nIndirectness (serious)d\nInflammatory neurologic \neventsa,e CriticalOne phase 2/3 RCT1,\none phase 1 RCT2 Zero events observed Unable to evaluate\nReactogenicity (grade ≥3)a,fImportantOne phase 2/3 RCT1,\none phase 1 RCT2 1.54 (1.40, 1.68) Indirectness (serious)d\na)Included data are among all Moderna RCT participants (aged ≥60 years).\nb)Phase 2/3 RCT: Any time after vaccination. Phase 1 RCT: Within 12 months after vaccination.\nc)Serious concern for inconsistency as the risk ratios observed in the phase 1 and phase 2/3 trials had different point estimat es.\nd)Serious concern for indirectness due to inclusion of adults aged 60 –74 years.\ne)Within 42 days after vaccination\nf)Within 7 days after vaccination\n1.Clinical trials.gov NTC:05127434. https://classic.clinicaltrials.gov/ct2/show/NCT05127434 . Wilson E, Goswami J, Baqui  AH, et al. Efficacy and Safety of an mRNA -Based RSV \nPreF  Vaccine in Older Adults. N Engl J Med. 2023 Dec 14;389(24):2233 -2244. doi: 10.1056/NEJMoa2307079. Plus additional data obtained directly from the manufacturer\n2.Clinical trials.gov NTC:04528719. https://clinicaltrials.gov/study/NCT04528719?term=NCT04528719 . Shaw CA, Essink  B, Harper C, et al. Safety and Immunogenicity of an \nmRNA -Based RSV Vaccine Including a 12 -Month Booster in a Phase I Clinical Trial in Healthy Older Adults. J Infect Dis. 2024 Feb 22:jiae081. doi: 10.1093/ infdis /jiae081. Epub  \nahead of print. PMID: 38385566. Plus additional data obtained directly from the manufacturer, only included those who receive d the phase 2/3 vaccine formulation or placeboModerna mRESVIA  in adults aged ≥75 years\nHarms\n34Summary of GRADE for Moderna mRESVIA  in adults aged ≥75 years\nOutcome ImportanceDesign\n(# of studies)FindingsEvidence\ntype\nBenefits\nRSV Lower Respiratory Tract \nDisease (L TRD)Important RCT (1)Vaccination with Moderna mRESVIA likely reduces RSV LRTD in \nadults aged ≥75 years.Moderate\nMedically attended RSV LRTD Critical RCT (1)Vaccination with Moderna mRESVIA may reduce medically attended \nRSV LRTD in adults aged ≥75 years.Low\nHospitalization for RSV \nrespiratory illnessCritical RCT (1)Vaccination with Moderna mRESVIA may reduce hospitalization for \nRSV respiratory illness in adults aged ≥75 years, but the effect is very \nuncertain.Very low\nSevere RSV respiratory illness \nrequiring O2/respiratory \nsupportImportant RCT (1) No data available to inform this outcomeUnable to \nevaluate\nDeath due to RSV respiratory \nillnessImportant RCT (1) Zero events observedUnable to \nevaluate\nHarms\nSerious adverse events Critical RCT (2)Vaccination with Moderna mRESVIA may result in little to no \ndifference in SAEs in adults aged ≥75 years.Low\nInflammatory neurologic \neventsCritical RCT (2) Zero events observedUnable to \nevaluate\nReactogenicity (grade ≥3) Important RCT (2)Vaccination with Moderna mRESVIA likely increases severe \nreactogenicity events in adults aged ≥75 years.Moderate\n35Additional information on benefits/harms for Moderna \nmRESVIA  in adults aged ≥75 years\n36▪Data on coadministration with mRESVIA  and other adult vaccines are \nlimited\n▪Coadministration of Moderna mRESVIA  with seasonal quadrivalent \ninfluenza vaccine as well as mRESVIA  with COVID -19 bivalent vaccine met \nnon -inferiority criteria for immunogenicity.1Other benefit/harms considerations: co -administration\n1.https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2024 -02-28-29/02 -RSV -Adults -Das -508.pdf  \n37▪How substantial are the desirable anticipated effects among adults aged ≥75 years?\n▪How substantial are the undesirable anticipated effects among adults aged ≥75 years?\n▪Do the desirable effects outweigh the undesirable effects among adults aged ≥75 \nyears?Benefits and Harms Moderna mRESVIA  in adults aged ≥75 years\nMinimal Small Moderate Large Varies Don’t know\nMinimal Small Moderate Large Varies Don’t know\nFavors intervention (Moderna mRESVIA RSV \nvaccine)\nFavors comparison (no vaccine)\nFavors both\nFavors neither\nUnclear\n38GRADE Framework: PICO Question\nPopulation Adults aged 60 –74 years at increased risk of severe RSV disease\nIntervention RSV Vaccine:\nModerna mRESVIA (50 μg,single dose IM)\nComparison No RSV vaccine\nOutcomes ▪RSV lower respiratory tract disease (LRTD)\n▪Medically attended RSV LRTD\n▪Hospitalization for RSV respiratory illness\n▪Severe RSV respiratory illness requiring supplemental oxygen or \nother respiratory support\n▪Death due to RSV respiratory illness\n▪Serious Adverse Events (SAEs)\n▪Inflammatory neurologic events (e.g., Guillain -Barré syndrome)\n▪Reactogenicity (grade ≥3)\n39Outcome Importance Data SourcesEffect Estimate, Vaccine \nefficacy (95% CI)aConcerns in certainty \nassessment\nRSV Lower Respiratory Tract Disease \n(L TRD)b,c Important\nOne Phase 3 RCT in adults \n≥60 years1\n• Mean efficacy follow up \nthrough 18 months \npost -vaccination per \nparticipant (median 19 \nmonths)d66.8% (41.5, 82.1%) None\nMedically attended RSV LRTDe,cCritical 39.0% ( -58.8, 78.1%)Indirectness (serious)f\nImprecision (serious)g\nHospitalization for RSV respiratory \nillnessc Critical 80.1% ( -363.7, 100%)h Indirectness (serious)f\nImprecision (very serious)i\nSevere RSV respiratory illness \nrequiring O2/respiratory supportc Important Not data available Unable to evaluate\nDeath due to RSV respiratory illnesscImportant Zero events observed Unable to evaluate\na)Calculated as (1 –  Incident Rate Ratio) x 100%. Events were included if they occurred >14 days post -vaccination.\nb)Included data are from participants aged ≥60 years with ≥1 comorbidity (chronic obstructive pulmonary disease [COPD], asthma,  chronic respiratory disease, heart failure, \ndiabetes mellitus, advanced liver disease, advanced renal disease). \nc)LRTD using co -primary endpoint of at LRTD with at least 3 signs or symptoms\nd)Efficacy follow -up through maximum 24 months postvaccination per participants (median 19 months)\ne)Included data are among all participants (aged ≥60 years).\nf)Serious concern for indirectness due to inclusion of adults without comorbidities.\ng)Serious concern for imprecision due to the confidence intervals containing absolute risk reduction estimates for which differ ent policy decisions might be considered\nh)VE calculated using 0.5 correction factor to account for zero events in the placebo group. Data cut off April 2023\ni)Very serious concern for imprecision due to the confidence intervals containing absolute risk reduction estimates for which d ifferent policy decisions might be considered and \nfragility of the estimate\n1. Clinical trials.gov NTC:05127434. https://classic.clinicaltrials.gov/ct2/show/NCT05127434 . Wilson E, Goswami J, Baqui  AH, et al. Efficacy and Safety of an mRNA -Based RSV PreF  Vaccine in \nOlder Adults. N Engl J Med. 2023 Dec 14;389(24):2233 -2244. doi: 10.1056/NEJMoa2307079. Plus additional data obtained directly from the manufacturerModerna mRESVIA  vaccine in adults aged 60 –74 years at increased risk of severe RSV disease\nBenefits: vaccine efficacy estimates\n40a)Included data are among all participants (aged ≥60 years).\nb)Phase 2/3 RCT: Any time after vaccination. Phase 1 RCT: Within 12 months after vaccination.\nc)Serious concern for inconsistency as the risk ratios observed in the phase 1 and phase 2/3 trials had different point estimat es.\nd)Serious concern for indirectness due to inclusion of adults without comorbidities.\ne)Within 42 days after vaccination\nf)Within 7 days after vaccination\n1. Clinical trials.gov NTC:05127434. https://classic.clinicaltrials.gov/ct2/show/NCT05127434 . Wilson E, Goswami J, Baqui  AH, et al. Efficacy and Safety of an mRNA -Based RSV PreF  Vaccine in \nOlder Adults. N Engl J Med. 2023 Dec 14;389(24):2233 -2244. doi: 10.1056/NEJMoa2307079. Plus additional data obtained directly from the manufacturer\n2. Clinical trials.gov NTC:04528719. https://clinicaltrials.gov/study/NCT04528719?term=NCT04528719 . Shaw CA, Essink  B, Harper C, et al. Safety and Immunogenicity of an mRNA -Based RSV \nVaccine Including a 12 -Month Booster in a Phase I Clinical Trial in Healthy Older Adults. J Infect Dis. 2024 Feb 22:jiae081. doi: 10.1093/ infdis /jiae081. Epub  ahead of print. PMID: 38385566. \nPlus additional data obtained directly from the manufacturer, only included those who received the phase 2/3 vaccine formulat ion or placeboOutcome Importance Data Sources Effect Estimate, Risk \nratio (95% CI)Concerns in certainty \nassessment\nSerious adverse events \n(SAEs)a,bCriticalOne phase 2/3 RCT1,\none phase 1 RCT2 1.00 (0.95, 1.05)Inconsistency (serious)c\nIndirectness (serious)d\nInflammatory \nneurologic eventsa,eCriticalOne phase 2/3 RCT1,\none phase 1 RCT2 Zero events observed Unable to evaluate\nReactogenicity (grade \n≥3)a,fImportantOne phase 2/3 RCT1,\none phase 1 RCT2 1.54 (1.40, 1.68) Indirectness (serious)dModerna mRESVIA  vaccine in adults aged 60 –74 years at increased risk \nof severe RSV disease\nHarms\n41Summary of GRADE for Moderna mRESVIA  vaccine in adults aged 60 –74 \nyears at increased risk of severe RSV disease\nOutcome​ ImportanceDesign\n(# of studies)​Findings​Evidence\ntype​\nBenefits\nRSV Lower Respiratory Tract \nDisease (LTRD)Important RCT (1)Vaccination with Moderna mRESVIA reduces RSV LRTD in adults aged 60 –\n74 years at increased risk of severe RSV disease.High\nMedically attended RSV LRTD Critical RCT (1)Vaccination with Moderna mRESVIA may reduce medically attended RSV \nLRTD in adults aged 60 –74 years at increased risk of severe RSV disease.Low\nHospitalization for RSV \nrespiratory illnessCritical RCT (1)Vaccination with Moderna mRESVIA may reduce hospitalization for RSV \nrespiratory illness in adults aged 60 –74 years at increased risk of severe \nRSV disease, but the effect is very uncertain.Very low\nSevere RSV respiratory illness \nrequiring O2/respiratory \nsupportImportant RCT (1) No data available to inform this outcomeUnable to \nevaluate\nDeath due to RSV respiratory \nillnessImportant RCT (1) Zero events observedUnable to \nevaluate\nHarms\nSerious adverse events​ Critical RCT (2)Vaccination with Moderna mRESVIA may result in little to no difference in \nSAEs in adults aged 60 –74 years at increased risk of severe RSV disease.Low\nInflammatory neurologic events Critical RCT (2) Zero events observedUnable to \nevaluate\nReactogenicity ​(grade ≥3) Important RCT (2)Vaccination with Moderna mRESVIA likely increases severe reactogenicity \nevents in adults aged 60 –74 years at increased risk of severe RSV disease.Moderate\n42Primary outcomeEfficacy (95% CI), \nmonths 0 –12aEfficacy (95% CI),\nmonths 12 –24a\nRSV LRTD with ≥2 lower \nrespiratory signs or \nsymptoms56%  (42, 67)\nMean 12 months follow -up per participant30%  (1, 51)\nMean 7 months follow -up per participant\nRSV LRTD with ≥3 lower \nrespiratory signs or \nsymptoms55%  (31, 71)\nMean 12 months follow -up per participant36%  (-13, 64)\nMean 7 months follow -up per participantModerna mRESVIA  vaccine efficacy against primary clinical \ntrial outcomes over time\nAbbreviations: CI: confidence interval, LRTD: lower respiratory tract disease\na.Nominal efficacy during 12 -month period. Not all trial participants contributing to estimate had full 12 months’ follow up time during the period. Mean \nper-participant follow -up during each period (reported below each estimate) was calculated by CDC using number of participants a nd total person -time \nprovided by manufacturer.\n43▪How substantial are the desirable anticipated effects among adults aged 60 –74 years at increased risk \nof severe RSV disease?\n▪How substantial are the undesirable anticipated effects among adults aged 60 –74 years at increased \nrisk of severe RSV disease?\n▪Do the desirable effects outweigh the undesirable effects among adults aged 60 –74 years at increased \nrisk of severe RSV disease?Benefits and Harms Moderna mRESVIA  in adults aged 60 –74 years at \nincreased risk of severe RSV disease\nMinimal Small Moderate Large Varies Don’t know\nMinimal Small Moderate Large Varies Don’t know\nFavors intervention (Moderna mRESVIA RSV \nvaccine)\nFavors comparison (no vaccine)\nFavors both\nFavors neither\nUnclear\n44\nValues and preferences\n- Do adults 75 and older feel the desirable effects of RSV vaccination are large relative to the \nundesirable effects? \n- Do adults 60 –74 at increased risk of severe RSV disease feel the desirable effects of RSV vaccination \nare large relative to the undesirable effects? \n- Is there important variability in how these adults value the main outcomes?\n456.5\n10.6\n10.712.2\n17.1\n25.132.7\n41.0\n33.148.6\n31.2\n31.1\n0 25 50 75 100Age ≥75 (N=326)Age 60 -74 (N=977)Age 18 -59 (N=2,799)\nWeighted %Very concerned Moderately concerned A little concerned Not at all concernedConcern about Getting RSV Disease Among Adults ≥60 Years of Age, by \nAge Group, Omnibus Surveys, April 4 –26, 2024 (N=4,102)\nOmnibus Surveys: data for this analysis were collected through the Ipsos KnowledgePanel  and NORC AmeriSpeak  Omnibus Surveys, which use probability -based panels to survey a nationally representative \nsample of U.S. adults aged 18 years and older. CDC fields questions about vaccination status, intent, knowledge, attitudes, b eliefs, and behaviors on each survey for 2 waves each month, for a combined sample \nsize of ~4,000 respondents. These slides present results from April 2024. Data were weighted to represent the non -institutionali zed U.S. population and mitigate possible non -response bias. All responses are self -\nreported.\n46RSV Vaccination Among Adults ≥60 Years of Age, by Age Group \nSeptember 2023 –May 2024 (n=156,281)\nNational Immunization Survey -Adult COVID Module (NIS -ACM)\nNational Immunization Survey -Adult COVID Module (NIS -ACM). The NIS -ACM is a random -digit -dial cellular telephone survey of adults age ≥18 years in the U.S. Respondents \nare sampled within all 50 states, District of Columbia, five local jurisdictions (Bexar County TX, Chicago IL, Houston TX, Ne w York City NY, and Philadelphia County PA), Guam, \nPuerto Rico, and the U.S. Virgin Islands (sampled in 2023 only). Data are weighted to represent the non -institutionalized U.S. p opulation. All responses are self -reported.\nhttps://www.cdc.gov/vaccines/imz -managers/coverage/rsvvaxview/adults -60-coverage -intent.html  24.430.732.3\n18.1\n010203040Vaccinated with RSV vaccine (%)\nWeek end dateAll adults 60+ 80+ 70-79 60-69\n47▪While we do not have any data specifically looking at how adults value estimated \nprotection against RSV in relation to potential risk of GBS, a few considerations: \n1.Adults are willing to accept some rate of vaccine -associated adverse events for the \nbenefit of preventing disease1 \n2.Individual baseline and vaccine -associated risk of GBS may differ by age group and \npresence of chronic conditions \n3.Willingness to accept risk of GBS after vaccination may differ by age and health \nstatus and perceived risk of RSV -associated disease2Risk of Guillain -Barre Syndrome (GBS)\n1.Scherer LD, Shaffer VA, Patel N, Zikmund -Fisher BJ. Can the vaccine adverse event reporting system be used to increase vaccine a cceptance and trust? Vaccine. 2016 May \n5;34(21):2424 -2429.  https://pubmed.ncbi.nlm.nih.gov/27049120/  \n2.Prosser LA, Payne K, Rusinak  D, et al. Valuing health across the lifespan: health state preferences for seasonal influenza illnesses in patients of differ ent ages. Value Health. \n2011;14(1):135 -143.  https://pubmed.ncbi.nlm.nih.gov/21211495/  \n48▪In the first RSV season after ACIP made a shared clinical decision -making \nrecommendation for adults 60 years and older, an estimated 20 –30% of U.S. adults in \nthis age group received RSV vaccination.\n▪Vaccination uptake was higher among adults ≥70 years than among adults 60 –69 years.\n▪We do not have data on how adults value risk of protection against RSV versus \npotential risk of GBS , but this may vary by age or other factors. Values: summary of the available evidence\nAdults 60 years and older\n49▪Do adults aged ≥75 years feel that the desirable effects of RSV \nvaccination are large relative to the undesirable effects?\n▪Is there important uncertainty about, or variability in, how much adults \naged ≥75 years value the main outcomes?Values\nNo Probably no Probably Yes Yes Varies Don’t know\nImportant uncertainty or variability\nProbably important uncertainty or variability\nProbably not important uncertainty or variability\nNo important uncertainty or variability\nNo known undesirable outcomes\n50▪Do adults aged 60 –74 years at increased risk of severe RSV disease feel \nthat the desirable effects of RSV vaccination are large relative to the \nundesirable effects?\n▪Is there important uncertainty about, or variability in, how much adults \naged 60 –74 years at increased risk of severe RSV disease value the main \noutcomes?Values\nNo Probably no Probably Yes Yes Varies Don’t know\nImportant uncertainty or variability\nProbably important uncertainty or variability\nProbably not important uncertainty or variability\nNo important uncertainty or variability\nNo known undesirable outcomes\n51\nIs it feasible to implement RSV vaccination for adults 75 and older ?\nIs it feasible to implement RSV vaccination for adults 60 –74 at increased risk of severe RSV disease ?Acceptability\nWould recommending RSV vaccination for adults 75 and older be acceptable to key stakeholders?\nWould recommending RSV vaccination for adults 60 –74 at increased risk of severe RSV disease  \nbe acceptable to key stakeholders?\nFeasibility\n52Based on survey data, physicians think shared clinical decision -making \nincreases time and confusion1\nKempe A, Lindley MC, O'Leary ST, et al. Shared Clinical Decision -Making Recommendations for Adult Immunization: What Do Physicia ns Think? J Gen Intern \nMed . 2021;36(8):2283 -2291. https://pubmed.ncbi.nlm.nih.gov/33528783/  . Numbers cited based on General Internal Medicine physician responses, N=281). 68% strongly agreed \nSCDM will require more \ntime with patients 44% either strongly or \nsomewhat agreed they find \nit hard to explain what a \nSCDM recommendation \nmeans to patients \n76% either strongly or \nsomewhat agreed SCDM \ncreates confusion42% either strongly or \nsomewhat agreed they \ndid not know how to \nimplement SCDM as \nintended by the ACIP\n53▪ SCDM conversations are challenging and time -consuming. \n▪ Compared to universal recommendations, SCDM does not have a clear call to \naction. \n▪ Standing orders - often used by medical assistants, nurses, and pharmacists – are \ndifficult under SCDM . \n▪ Approximately 80%  of all older adult RSV vaccinations have been given in \npharmacies. Not all providers who give vaccines are comfortable with the SCDM \nconversation or feel it is within their scope of practice. \n▪ In the specific instance of RSV vaccines, there are also concerns about the ability to \ncomplete the type of risk -benefit discussion intended by ACIP with the RSV SCDM \nrecommendation.CDC and ACIP have heard feedback that the RSV SCDM \nrecommendation has been difficult to implement\nDr. Carla Black, ACIP Meeting February 2024: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2024 -02-28-29/04 -RSV -Adults -Black -508.pdf  \n54▪Vaccine acquisition cost relatively high\n–Costly upfront investment to carry RSV vaccines\n▪RSV vaccine billed under Medicare  Part D\n–Millions of Medicare beneficiaries are not enrolled in Part D\n–Part D generally described as more challenging to access and implement \nthan Part B so providers may be less likely to carry vaccine in their \npractices and instead refer to pharmaciesFinancial and insurance barriers \n55▪Multiple adult RSV vaccine products\n▪Different storage and handling requirements\n–Moderna mRESVIA  requires frozen storage or if refrigerated use within \n30 days\n▪Adult vaccine schedule is increasingly complex including \nmultiple products with different schedulesSchedule complexity \n56Acceptability and Feasibility: Summary of the available evidence \nAll adults aged 75 years and older\n•Makes vaccination the “default” \n•Easier to incorporate into standing \norders, clinical decision support, and \nmessaging\n•Covers those at highest risk without \nasking providers to do extensive \nindividualized risk assessment•“Universal” RSV recommendation \nonly for some ages\n•Ongoing challenge in complexity \nof adult schedule\n•Repeated recommendation \nchanges may cause confusion \n57Acceptability and Feasibility: Summary of the available evidence \nRisk -based recommendation adults aged 60 –74 years\n•Compared with a shared clinical \ndecision -making recommendation, a \nrisk-based recommendation will \nprovide more clarity to providers and \npublic about who should  get an RSV \nvaccine\n•Easier to incorporate into standing \norders, clinical decision support,  and \nmessaging•Risk -based recommendations are \nstill more challenging to \nimplement than universal \nrecommendations\n•Eligible risk factors for RSV \nvaccination will not align with \nother adult vaccines\n•Repeated recommendation \nchanges may cause confusion \n58▪Would recommending RSV vaccines for adults aged ≥75 years \nbe acceptable to key stakeholders?\n▪Would recommending RSV vaccines for adults aged 60 –74 \nyears at increased risk of severe RSV disease be acceptable to \nkey stakeholders?Acceptability\nNo Probably No Probably Yes Yes Varies Don’t know\nNo Probably No Probably Yes Yes Varies Don’t know\n59▪Is it feasible to implement protein subunit RSV vaccination \namong  adults aged ≥75 years?\n▪Is it feasible to implement Moderna mRESVIA  vaccination \namong adults aged ≥75 years?Feasibility\nNo Probably No Probably Yes Yes Varies Don’t know\nNo Probably No Probably Yes Yes Varies Don’t know\n60▪Is it feasible to implement protein subunit RSV vaccination \namong adults aged 60 –74 years at increased risk of severe \nRSV disease?\n▪Is it feasible to implement Moderna mRESVIA  vaccination \namong adults aged 60 –74 years at increased risk of severe \nRSV disease?Feasibility\nNo Probably No Probably Yes Yes Varies Don’t know\nNo Probably No Probably Yes Yes Varies Don’t know\n61\nResource Use\nIs an RSV vaccine program for adults a reasonable and efficient allocation \nof resources for:\n•Adults 75 and older?\n•Adults 60 –74 at increased risk of severe RSV disease?\n62▪RSV vaccination is likely cost -effective for: \n–Adults aged 75 years and older \n–Adults aged 60 –74-year with risk factors for severe RSV disease \n▪RSV vaccination is likely NOT cost -effective in adults aged 60 –74 years without  risk \nfactors.\n–Therefore, a universal  RSV vaccination in adults aged 60 –74 years is likely NOT a reasonable and efficient allocation \nof societal resources\n▪There remains substantial uncertainty in key parameters that impact cost \neffectiveness:\n–Uncertainty in incidence of medically attended RSV illness, particularly hospitalizations\n–Uncertainty in RSV -attributable mortality\n–Uncertainty in duration of protection from a single dose of RSV vaccination\n–Real -world vaccine effectiveness of Moderna mRESVIA ; analyses currently rely on clinical trial efficacy estimates\n▪For all 3 manufacturers, Work Group felt that if RSV vaccine list prices were \nsubstantially reduced, then RSV vaccination may be a cost -effective intervention for \na broader adult population.Work Group considerations regarding societal resource use \ntoward RSV vaccination in older adults at current list prices\n63▪Is protein subunit RSV vaccination a reasonable and efficient allocation of resources \nin adults aged ≥75 years ?\n▪Is Moderna mRESVIA  vaccination  in adults  aged ≥75 years a reasonable and efficient \nallocation of resources?Resource use\nNo Probably No Probably Yes Yes Varies Don’t knowNo Probably No Probably Yes Yes Varies Don’t know\n64▪Is protein subunit RSV  vaccination a reasonable and efficient allocation of resources \nin adults aged 60 –74 years at increased risk of severe RSV disease ?\n▪Is Moderna mRESVIA  vaccination  in adults aged 60 –74 years at increased risk of \nsevere RSV disease a reasonable and efficient allocation of resources?Resource use\nNo Probably No Probably Yes Yes Varies Don’t knowNo Probably No Probably Yes Yes Varies Don’t know\n65\nEquity\nWhat would be the impact on health equity of recommending RSV \nvaccination for:\n•Adults 75 and older?\n•Adults 60 –74 at increased risk of severe RSV disease?\n66Median age of non -pregnant adults aged ≥18 years with RSV -associated \nhospitalizations by race and ethnicity* — RSV-NET, 2014 –2015 to 2022 –\n2023\nUnweightedWeighted\n%Median \nAgeInterquartile \nrange (IQR)\nOverall 17,847 - 69 (58–81)\nWhite 10,755 62.2 73 (63-82)\nBlack 3,529 20.4 62 (50-71)\nHispanic 1,434 8.3 62 (48-76)\nAsian or Pacific Islander 1,020 5.9 73 (59-83)\nAmerican Indian or Alaska \nNative90 0.5 64 (54-73)\nMultiple races 89 0.5 75 (58-84)\nUnknown 367 2.1 68 (57-78)\n*Black, White, American Indian/Alaska Native and Asian/Pacific Islander people were categorized as non -Hispanic; Hispanic people  could be of any race.Median age of \nhospitalization is \nlower among Black, \nHispanic, and \nAmerican \nIndian/Alaska Native \npersons than White \nand Asian/Pacific \nIslander persons. \n67050100150200250300350400450500\nAge 60 –74 years Age ≥75 yearsRSV -associated hospitalizations per \n100,000 populationBlack\nHispanic\nWhite\nAsian & Pacific IslanderRSV -associated hospitalization rates by age group and race \nand ethnicity*, RSV -NET, 2018 –2019\nhttps://www.cdc.gov/rsv/research/rsv -net/index.html  Unpublished data. Rates are adjusted using multipliers for the frequency of RSV testing during each season and the sensitivit y of RSV \ndiagnostic tests. Error bars represent 95% confidence intervals. Estimated rates exclude recorded hospitalizations among preg nan t adults. Black, White, and Asian/Pacific Islander people \nwere categorized as non -Hispanic; Hispanic people could be of any race. Hospitalization rates among American Indian and Alaska N ative persons are not shown due to small numbers. There \nmay be unmeasured confounding, especially in the oldest age group. Although incidence appears lower in Black adults 75 and ol der than in White adults, if Black adults are less likely to \nsurvive to age 80 or 90 years, then differences in underlying age distribution may be driving this finding. Black adults had a \nhospitalization rate 1.5x  \nhigher than White adults\n68Weekly cumulative RSV vaccination coverage, by race and ethnicity, \nMedicare fee -for-service beneficiaries aged ≥65 years and enrolled in a Part \nD plan, United States\nData source: C enters for Medicare & Medicaid Services Chronic Conditions Warehouse. Estimates are based on data released by CMS through Mar ch 30, 2024. Overall includes persons categorized as ‘Unknown’ \nfor race and ethnicity category. Data can be accessed at : https://www.cdc.gov/vaccines/imz -managers/coverage/rsvvaxview/adults -65yrs -older -coverage.html  0510152025\n8/5/2023\n8/12/2023\n8/19/2023\n8/26/2023\n9/2/2023\n9/9/2023\n9/16/2023\n9/23/2023\n9/30/2023\n10/7/2023\n10/14/2023\n10/21/2023\n10/28/2023\n11/4/2023\n11/11/2023\n11/18/2023\n11/25/2023\n12/2/2023\n12/9/2023\n12/16/2023\n12/23/2023\n12/30/2023\n1/6/2024\n1/13/2024\n1/20/2024\n1/27/2024\n2/3/2024\n2/10/2024\n2/17/2024\n2/24/2024\n3/2/2024\n3/9/2024\n3/16/2024\n3/23/2024\n3/30/2024White, Non-\nHispanic\nOverall\nAsian, Non-\nHispanic\nBlack, Non-\nHispanic\nHispanic\n6936.1*29.8*22.5*18.020.8*28.4*23.7*14.87.0*24.519.324.5*24.9*30.923.9*26.625.322.0*25.921.6*26.118.3*27.5\n0 5 10 15 20 25 30 35 40 45Advanced degreeCollege graduateSome collegeHigh school or less (Ref)Income unknownAbove poverty, >=$75KAbove poverty, <$75KBelow poverty (Ref)UninsuredInsured (Ref)Rural (Ref)SuburbanUrbanHHS Region 10HHS Region 9HHS Region 8HHS Region 7HHS Region 6HHS Region 5HHS Region 4HHS Region 3HHS Region 2HHS Region 1 (Ref)\nWeighted % (95% CI)RSV Vaccination Coverage Among Adults ≥60 Years of Age, by end of \nMarch 2024 (n=156,281)\nNational Immunization Survey -Adult COVID Module (NIS -ACM)\nVaccination coverage was \nsignificantly lower among \nadults in rural areas \n(19.3%), uninsured  (7.0%), \nthose with lower \nhousehold income , and \nwith educational level of \nhigh school or less (18.0%).\nHHS Regions\n1: CT,ME,MA,NH,RI,VT\n2: NJ,NY,PR,VI\n3: DE,DC,MD,PA,VA,WV\n4: AL,FL,GA,KY,MS,NC,SC,TN\n5: IL,IN,MI,MN,OH,WI\n6: AR,LA,NM,OK,TX\n7: IA,KS,MO,NE\n8: CO,MT,ND,SD,UT,WY\n9: AZ,CA,HI,NV,GU\n10: AK,ID,OR,WACI: 95% confidence interval; Ref: Referent category.\n*Statistically significant at p<0.05 compared to the referent category.\nKaplan -Meier estimates are based on cumulative data through April 27, 2024.\n70Equity:  Summary of the available evidence\nAll adults aged 75 years and older\n•Practicality and value of issuing \na simple and clear message \nmay remove barriers  to \nvaccination\n•Adults with undiagnosed  \nchronic medical conditions \nwould be included in the \nrecommendation•Universal recommendations do \nnot guarantee equity; even if \ncoverage increases across all \ngroups, disparities between \ngroups may remain\n71Equity:  Summary of the available evidence\nAdults aged 60 –74 years at increased risk of severe RSV \ndisease\n•Clarifying who is at risk may  \nremove barriers   to vaccination\n•May increase coverage among \nracial/ethnic minority groups in \nwhom prevalence of chronic \nconditions is higher in 60 –74 \nage group•Adults with undiagnosed  \nchronic medical conditions may \nbe deemed ineligible for \nvaccination under a risk -based \nrecommendation; under shared \nclinical decision -making, some \nof these adults may have \nobtained RSV vaccination\n72▪What would be the impact on health \nequity of recommending RSV vaccination \nin adults aged ≥75 years?▪What would be the impact on health \nequity of recommending RSV vaccination \nin adults aged 60 –74 years at increased \nrisk of severe RSV disease?Equity\nReduced\nProbably reduced\nProbably no impact\nProbably increased\nIncreased\nVaries\nDon’t knowReduced\nProbably reduced\nProbably no impact\nProbably increased\nIncreased\nVaries\nDon’t know\n73\nSummary\n74Domain Question Work Group Judgements\nAdults aged 75 years and older Protein Subunit \nRSV Vaccines \n(Pfizer and GSK)Moderna\nPublic Health \nProblemIs RSV of public health importance? Yes\nBenefits and \nHarmsHow substantial are the desirable anticipated effects? Moderate/Large Moderate/Large\nHow substantial are the undesirable anticipated effects? Small/Moderate Small\nDo the desirable effects outweigh the undesirable effects? Favors intervention Favors intervention\nValuesDoes the target population feel the desirable effects are large \nrelative to the undesirable effects?Yes/Probably yes\nIs there important variability in how patients value the \noutcomes?Probably not important variability\nAcceptability Is the intervention acceptable to key stakeholders? Yes\nFeasibility Is the intervention feasible to implement? Yes/Probably yes Yes/Probably yes\nResource UseIs the intervention a reasonable and efficient allocation of \nresources?Yes/Probably yes Yes/Probably yes\nEquity What would be the impact on health equity? Increased/Probably increased\n75Domain Question Work Group Judgements\nAdults aged 60–74 years at increased risk of \nsevere RSV disease Protein Subunit \nRSV Vaccines \n(GSK and Pfizer)Moderna\nPublic Health \nProblemIs RSV of public health importance? Yes\nBenefits and \nHarmsHow substantial are the desirable anticipated effects? Moderate/Large Moderate/Large\nHow substantial are the undesirable anticipated effects? Small/Moderate Small\nDo the desirable effects outweigh the undesirable effects? Favors intervention Favors intervention\nValuesDoes the target population feel the desirable effects are large \nrelative to the undesirable effects?Probably yes\nIs there important variability in how patients value the \noutcomes?Probably not important variability\nAcceptability Is the intervention acceptable to key stakeholders? Yes/Probably yes\nFeasibility Is the intervention feasible to implement? Yes/Probably yes Yes/Probably yes\nResource UseIs the intervention a reasonable and efficient allocation of \nresources?Yes/Probably yes Yes/Probably yes\nEquity What would be the impact on health equity? Probably increased\n76▪The shared clinical decision -making (SCDM) recommendation was made in the setting of \nuncertainty about both the estimated benefits and potential risks of RSV vaccination. \n▪Now there is real -world evidence of robust protection against RSV -associated hospitalization \nduring the first season after vaccination among adults 60 and older, including among adults 75 \nand older and adults with chronic medical conditions.\n▪On the other hand, uncertainty remains regarding the magnitude of potential risk of Guillain -\nBarre syndrome (GBS).\n▪The Work Group believes the GBS signal continues to warrant close attention and additional \nfollow -up.\n▪A transition from SCDM to a universal recommendation among adults 75 years and older \nand a risk -based recommendation among adults aged 60 –74 years and is intended to: \n–Maximize vaccination among persons most likely to benefit among whom we now have \nreal -world evidence of protection \n–Minimize vaccination among persons least likely to benefit  while additional safety data \naccrueWork Group Considerations\n77▪The Work Group discussed the role of potential preferential recommendations \nbetween products, but felt that the strength of the available evidence did not \nmeet the standard for a preferential recommendation at this time.  \n▪Reasons cited included: \n–Current safety analyses are interim and based on a small numbers of GBS cases.\n–Unknown relative duration of protection across products\n–Need for revaccination and potential risk of GBS associated with additional \ndoses unknown\n–Changes based on limited evidence may have unintended programmatic \nconsequences Additional Work Group discussions\n78Evidence to Recommendations Framework\nSummary: Work Group Interpretations\nBalance of \nconsequencesUndesirable \nconsequences \nclearly outweigh \ndesirable \nconsequences in \nmost settingsUndesirable \nconsequences \nprobably \noutweigh \ndesirable \nconsequences in \nmost settingsThe balance \nbetween \ndesirable and \nundesirable \nconsequences is \nclosely balanced \nor uncertainDesirable \nconsequences \nprobably \noutweigh \nundesirable \nconsequences in \nmost settingsDesirable \nconsequences \nclearly outweigh \nundesirable \nconsequences in \nmost settingsThere is \ninsufficient \nevidence to \ndetermine the \nbalance of \nconsequences\nBalance of \nconsequencesUndesirable \nconsequences \nclearly outweigh \ndesirable \nconsequences in \nmost settingsUndesirable \nconsequences \nprobably \noutweigh \ndesirable \nconsequences in \nmost settingsThe balance \nbetween \ndesirable and \nundesirable \nconsequences is \nclosely balanced \nor uncertainDesirable \nconsequences \nprobably \noutweigh \nundesirable \nconsequences in \nmost settingsDesirable \nconsequences \nclearly outweigh \nundesirable \nconsequences in \nmost settingsThere is \ninsufficient \nevidence to \ndetermine the \nbalance of \nconsequencesAmong adults aged 60–74 years at increased risk of severe RSV disease :Among all adults aged ≥75 years :\n79Evidence to Recommendations Framework\nSummary: Work Group Interpretations – Is there sufficient information to move \nforward with a recommendation?\nAmong adults aged 60–74 years at increased risk of severe RSV disease :Among all adults aged ≥75 years :\nYes NoYes No\n80Evidence to Recommendations Framework\nSummary: Work Group Interpretations\nType of recommendation, all adults aged ≥75 years\n•We recommend the intervention\nType of recommendation, adults aged 60 –74 years at increased risk of severe RSV \ndisease\n•We recommend the intervention\n811.ACIP recommends adults 75 years of age and older receive a single dose \nof RSV vaccine.a,b\n2.ACIP recommends adults 60 –74 years of age who are at increased risk of \nsevere RSV diseasec receive a single dose of RSV vaccine.a,bProposed ACIP vote language\na.RSV vaccination is recommended as a single lifetime dose only. Persons who have already received RSV vaccination \nare NOT recommended to receive another dose. \nb.These recommendations would supplant the current recommendation that adults 60 years of age and older may \nreceive RSV vaccination, using shared clinical decision -making. Adults 60 –74 years of age who are not at increased \nrisk of severe RSV disease would NOT be recommended to receive RSV vaccination.\nc.CDC will publish Clinical Considerations that describe chronic medical conditions and other risk factors for severe \nRSV disease for use in this risk -based recommendation.\n82\nShould adults aged 50 –59 years at increased \nrisk of severe RSV disease  be recommended \nto receive a single dose of RSV vaccination?\n83\nEtR  Domain: Public Health Problem\nIs the problem of public health importance among adults aged 50 –59 years \nat increased risk of severe RSV disease?\n84Estimated annual number  of \nRSV-associated \nhospitalizations * among \nadults aged ≥18 years by age \ngroup and year, RSV -NET, \n2016 –17 to 2019 –20\n0 20,000 40,000 60,000 80,000 100,000≥80 \n75–79\n70–74\n65–69\n60–64\n55–59\n50–54\n18–49\nAnnual RSV -associated hospitalizationsAge \ngroup, \nyears2016 –17 2017 –18 2018 –19 2019 –20\nPreliminary unpublished data. Hospitalization counts  are adjusted \nusing multipliers for the frequency of RSV testing during each season \nand the sensitivity of RSV diagnostic tests. Error bars represent 95% \nconfidence intervals.\n*Estimated hospitalizations exclude recorded hospitalizations among \npregnant adults.\nhttps://www.cdc.gov/rsv/research/rsv -net/index.html  Estimated  10,000 – 20,000 \nannual RSV -associated \nhospitalizations  in \nU.S. adults aged 50–59 yearsSurveillance \nseason:\n85RSV -associated hospitalization rates among community -dwelling adults \naged ≥50 years with chronic medical conditions, 2017 –2018 season\nBMI: Body Mass Index (kg/m2), COPD: Chronic Obstructive Pulmonary Disease. Data are preliminary and unpublished. Rates of laboratory -confirmed RSV -associat ed hospitalization account for under -detection of RSV infection among hospitalized adults and \nsensitivity of diagnostic tests. Poisson regression using Monte Carlo simulation estimated rates and 95% confidence intervals  (represented by error bars). Rates for community -dwelling adults exclude residents of nursing homes and long -term care facilities \nand are not adjusted for sex or race/ethnicity group.0200400600\n50–59\n60–74\n≥75\n50–59\n60–74\n≥75\n50–59\n60–74\n≥75\n50–59\n60–74\n≥75\n50–59\n60–74\n≥75\n50–59\n60–74\n≥75\n50–59\n60–74\n≥75\n50–59\n60–74\n≥75\n50–59\n60–74\n≥75\n50–59\n60–74\n≥75\nNone of\nThese\nConditionsChronic\nKidney\nDiseaseCOPD Severe \nobesity\n(BMI ≥40)Asthma Coronary\nArtery\nDiseaseDiabetes\nmellitusStroke Obesity\n(BMI 30 –\n39)Current\nsmokerRSV-associated hospitalization rate \n(per 100,000)\nCommunity -dwelling adults \nwith none of these conditionsCommunity -dwelling adults \nwith each condition\n////////\n//////////////////\n86▪Is RSV of public health importance among adults aged 50–59 \nyears at increased risk of severe RSV disease? Public Health Problem: Work Group interpretation\nNoProbably \nNoProbably \nYesYes VariesDon’t \nknow\n87\nEtR  Domain: Benefits and Harms 50 –59\n- How substantial are the desirable anticipated effects?\n- How substantial are the undesirable anticipated effects?\n- Do the desirable effects outweigh the undesirable effects?\n88GRADE Framework: PICO Question\nPopulation Adults aged 50 –59 at increased risk of severe RSV disease\nIntervention RSV Vaccine:\nGSK AREXVY (1 dose IM)\nComparison No RSV vaccine\nOutcomes ▪RSV lower respiratory tract disease (LRTD)\n▪Medically attended RSV LRTD\n▪Hospitalization for RSV respiratory illness\n▪Severe RSV respiratory illness requiring supplemental oxygen or other \nrespiratory support\n▪Death due to RSV respiratory illness\n▪Serious Adverse Events (SAEs)\n▪Inflammatory neurologic events (e.g., Guillain -Barré syndrome)\n▪Reactogenicity (grade ≥3)\n89a) The manufacturer calculated GMR as Cohort 2 / Cohort 1a. However, here, the reciprocal is shown: Cohort 1a / Cohort 2. GMR va lues >1 indicate higher \nGMTs in Cohort 1a (adults 50 –59 at increased risk), compared with Cohort 2 (adults ≥60).\nb) Noninferiority objective was lower bound of the confidence interval ≥0.67, when evaluating the GMR Cohort 1a / Cohort 2.\nc) Serological assays for the determination of antibodies against RSV -A are performed by neutralization assay. The corresponding an tibody titers were \nexpressed in ED60 (serum estimated dilution inducing 60% inhibition in plaque -forming units). Assessed at Day 31 , where Day 1 w as day of vaccination\nd) Serological assays for the determination of antibodies against RSV -B are performed by neutralization assay. The corresponding an tibody titers were \nexpressed in ED60. Assessed at Day 31 , where Day 1 was day of vaccination.\n1. https://clinicaltrials.gov/study/NCT05590403 , https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2023 -10-25-26/02 -gerber -adult -RSV -\n508.pdf , unpublished data obtained from manufacturern GMT (95% CI),\n30 days post -vaccinationn GMT (95% CI),\n30 days post -vaccinationGMR (95% CI)a, \nCohort 1a vs. \nCohort 2Met \nNoninferiority \nObjectiveb\nCohort 1a: Adults aged 50 –59 years at \nincreased risk of severe RSV diseaseCohort 2: Adults aged ≥60 years\nRSV-Ac343 8922.7 (8118.2, 9806.9) 342 7440.1 (6768.4, 8178.5) 1.20 (1.05, 1.37) Yes\nRSV-Bd343 10054.7 (9225.4, 10958.7) 341 8062.8 (7395.9, 8789.9) 1.25 (1.10, 1.41) Yes\nAbbreviations: CI = confidence interval; GMT = geometric mean titer; GMR = geometric mean ratioGSK AREXVY vaccine in adults aged 50 –59 years at increased risk of severe RSV disease\nBenefits: Geometric Mean Ratio (GMR) of neutralizing antibody titers1\n90Summary of GRADE for GSK AREXVY in adults aged 50 –59 years at increased risk of \nsevere RSV disease\nOutcome ImportanceDesign\n(# of \nstudies)Findings\nIn adults aged 50 -59 years at increased risk of severe RSV disease:Evidence\ntype\nBenefits\nRSV Lower Respiratory \nTract Disease (L TRD)Important RCT (1) Vaccination with GSK AREXVY likely reduces RSV LRTD Moderate\nMedically attended RSV \nLRTDCritical RCT (1) Vaccination with GSK AREXVY likely reduces medically attended RSV LRTD Moderate\nHospitalization for RSV \nrespiratory illnessCritical RCT (1)Vaccination with GSK AREXVY may reduce hospitalization for RSV respiratory \nillnessVery Low\nSevere RSV respiratory \nillness requiring \nO2/respiratory supportImportant RCT (1)Vaccination with GSK AREXVY may reduce severe RSV respiratory illness \nrequiring supplemental O2 or other respiratory supportVery Low\nDeath due to RSV \nrespiratory illnessImportant RCT (1) Zero events observedUnable to \nevaluate\nHarms\nSerious adverse events Critical RCT (1)Vaccination with GSK AREXVY may result in little to no difference in serious \nadverse eventsLow\nInflammatory neurologic \neventsCritical RCT (1) Zero events observedUnable to \nevaluate\nReactogenicity (grade ≥3) Important RCT (1) Vaccination with GSK AREXVY increases severe reactogenicity events Moderate\n91Additional information on benefits/harms for adults aged \n50–59 years at increased risk of severe RSV disease\n92Per 1 Million Doses of GSK AREXVY Administered to Adults Aged 50 –59 \nYears at Increased Risk of Severe RSV Disease :\n1.Range of outcomes avertable was calculated using published 95% confidence intervals (outpatient only) and adjusted 95% confid ence interval of RSV -associated incidence of the outcome observed in RSV -NET\n2. FDA self -controlled case series analysis, among CMS Medicare beneficiaries ≥65 years with Parts A, B, and D coverage who did not  have a GBS claim in the 365 days before vaccination. Analysis based on \ndiagnoses of GBS in inpatient claims data in risk interval (1 -42 days after RSV vaccination) compared to control interval (43 -90 days after RSV vaccination). GBS cases identified using ICD -10 diagnosis of \nGBS in primary position of inpatient claims coding. Estimates adjusted for outcome -dependent observation time, positive predicti ve value of diagnostic codes in identifying chart -confirmed GBS cases, and \nseasonality. Analysis includes patients with RSV vaccinations  only through October 8, 2023 to allow for 90 -day post -vaccination  observation and 90% or greater claims data completeness. Claims data \nthrough April 6, 2024. \n3. Although CMS data were limited to Medicare beneficiaries aged ≥65 years, results are extrapolated here to adults aged 50 -59 year s.\n4. Self -controlled case series analysis estimated attributable risk of 3 (95% CI: -3, 10) GBS cases. However, the range was truncat ed at zero for Benefit/Risk analyses.Estimated RSV -Associated Outcomes1 Preventable over 2 RSV Seasons  vs. potential cases of GBS\n(positive predictive value -adjusted  attributable risk of GBS in FDA -CMS partnership data among adults \naged ≥65 years, 42 -day risk interval2,3)\n3 (range 0–10)4 attributable  cases of GBS80 330 1,500 \n -  1,000  2,000  3,000  4,000  5,000  6,000  7,000Hospitalizations\nICU Admissions\nDeaths\n(30–200)(130 –800)(600 –3,700)\n93▪Revaccination at 12 months does not appreciably increase efficacy, compared with a \nsingle dose.\n▪Optimal timing of re -vaccination is unknown. \n▪No available clinical trial immunogenicity, efficacy, or safety data in severely immune \ncompromised persons (e.g., hematopoietic cell or solid organ transplant recipients).As reviewed for adults 60 and older, there are a number of \nadditional considerations \n94▪How substantial are the desirable anticipated effects among adults aged 50 –59 years at increased risk \nof severe RSV disease\n▪How substantial are the undesirable anticipated effects among adults aged 50 –59 years at increased \nrisk of severe RSV disease?\n▪Do the desirable effects outweigh the undesirable effects among adults aged 50 –59 years at \nincreased risk of severe RSV disease?Benefits and Harms GSK AREXVY vaccine in adults aged 50 –59 at \nincreased risk of severe RSV disease\nMinimal Small Moderate Large Varies Don’t know\nMinimal Small Moderate Large Varies Don’t know\nFavors intervention (GSK AREXVY)\nFavors comparison (no vaccine)\nFavors both\nFavors neither\nUnclear\nMajority opinion Minority opinion\n95Evidence to Recommendations Framework\nSummary: Work Group Interpretations\nYes NoAmong adults aged 50–59 years at increased risk of severe RSV disease :\nIs there sufficient information to move forward with \na recommendation? \nAs of the June 26, 2024 ACIP meeting, the Work Group majority \nhas concluded there is currently insufficient evidence to make a \nrecommendation regarding RSV vaccination in adults 50 –59 \nyears at today’s meeting.\n96\nWork Group Considerations on the use \nof GSK AREXVY in adults 50 –59 years \nat increased risk of severe RSV disease \n97▪As demonstrated during the public health problem domain, the majority \nof the Work Group felt that RSV -associated disease is or probably is a \npublic health problem among adults aged 50 -59 years at increased risk of \nsevere RSV disease. \n▪This opinion is NOT a recommendation against  the use of RSV vaccine in \nadults aged 50 –59 years. \n▪Rather, the Work Group believes more information is needed to make a \npopulation -level policy recommendation. This represents an opinion that additional information is needed to \ndetermine the best policy for RSV vaccination in adults aged 50 –59 years. \n98▪Among adults aged 50 –59 years, in whom \nthe absolute rates of RSV -associated \ndisease are lower, the balance of risk and \nbenefits is more uncertain than among \nolder age groups.\n▪The Work Group recognizes that p ostponing \na policy recommendation may mean some \nadults aged 50 –59 years who might benefit \nfrom RSV vaccination will not receive a dose \nthis fall.The decision to postpone making a recommendation is primarily driven by \nuncertainty in the balance of estimated benefits of RSV vaccine and potential risk \nof GBS, specifically among adults aged 50 –59 years \nThe Work Group will \ncontinue active \ndeliberation on the best \npolicy recommendation in \nthis age group as more \ndata become available and \nwill bring a \nrecommendation for ACIP’s \nconsideration as soon as \nthe Work Group believes \nthere is sufficient evidence. \n99▪At least one complete season of safety surveillance data. \n–Depending on certainty of findings, additional data may be needed. \n▪Immunobridging  data in adults with immune compromise. \n–Clinical trials including adults with immune compromise are underway. \n▪Data on duration of protection and immune response after re -\nvaccination\n–Work Group has expressed concern that to date there are no data showing re -\nvaccination will restore protection if efficacy wanes over time.\n–While restoration of protection with re -vaccination is likely, efficacy in GSK’s pivotal \nphase III trial did not improve after re -vaccination at a 12 -month interval.\n–GSK immunogenicity data at 12 - and 24 -month re -vaccination intervals have shown a \nweaker humoral immune response, compared with the response after dose 1. Before making a recommendation for adults aged 50 –59 years the Work \nGroup would like to review additional data\n100The Work Group recognizes equity is an important concern in the use of RSV \nvaccines in adults aged 50 –59 years and they considered equity in their \ndeliberations. \n101▪This includes adults aged 50 –59 years and pending licensure, use of RSV \nvaccine in adults aged <50 years. \n▪The Work Group will continue to review data available from clinical trials, \nreal -world vaccine effectiveness, and safety monitoring.\n▪While the timeline of availability of sufficient safety and other data is \nunknown for a recommendation in adults 50–59 the Work Group will \npresent to ACIP the status of their deliberations as soon as there are \nupdated considerations. The Work Group is committed to ongoing assessment of \nRSV vaccination in adults\n102\nFor more information, contact CDC\n1-800 -CDC -INFO (232 -4636)\nTTY:  1 -888 -232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention.\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\n\n103\nBack -Up Slides \n104Prevalence of ≥1 chronic medical condition among adults 75 and older is at least 45%  using a narrow \ndefinition of chronic medical conditions* and may be as high as 71% when using a broad definition** \nNational Health and Nutrition Examination Survey (NHANES), 2015 –2018.\n*Narrow definition , at least one of:\n•Serious heart disease\n•Diabetes with complication\n•Chronic obstructive pulmonary disease\n•Asthma\n•Severe obesity (BMI ≥40 kg/m2)\n•Liver condition\n•Chronic kidney disease, stage 4 or 5\n**Broad definition , as above, OR:\n•Diabetes with or without  complication\n•Chronic kidney disease, stage 3, 4, or 5\n•Cancer or malignancy in past 2 years\nBMI: body mass index\nSOURCE: National Center for Health Statistics (NCHS), National Health and Nutrition Examination Survey (NHANES), 2015 –2018. All estimates are crude estimates with no age adjustment and age is age at interview. Error bars represent Korn and Graubard  95% confidence intervals. NHANES is representative of the civilian, non -institutionalized U.S. population. For “narrow” \ndefinition: Severe obesity was defined as BMI ≥40 kg/m2. Diabetes with complication was defined as 1) having diabetes: self -reported diabetes, fasting plasma glucose ≥126 mg/dL, or he moglobin A1c ≥6.5%, AND 2) having one of the following complications of diabetes assessed within the survey: serious heart di sease as defined below, chronic kidney disease (stage 3, 4, or 5) defined \nas estimated glomerular filtration rate (eGFR) ˂60 (stages 3 –5) further defined below, or having self -reported diabetes and having a doctor previously told them that diabetes a ffected their eyes or that they have retinopathy. Other complications of diabetes are not included in this definition. Seriou s heart disease was defined based on self -report as diagnosed congestive heart failure, \ncoronary heart disease, angina, or heart attack, or angina grades 1 or 2 determined by the Rose Angina Questionnaire. Asthma was  defined as self -reporting ever being diagnosed with asthma and still having asthma. Chronic kidney disease was defined as estim ated glomerular filtration rate (eGFR) ˂30 (stages 4 –5), and using a forward equation for adjustment of creatinine because of \nmethods changes. eGFR calculated using the 2021 CKD -EPI creatinine equation (https://www.nejm.org/doi/10.1056/NEJMoa2102953). Ur ine albumin is not included in this definition. Chronic obstructive pulmonary disease (COPD) was defined as self -reported diagno sed COPD, emphysema, or current chronic bronchitis. Liver condition was defined as self -reporting ever being \ndiagnosed with any kind of liver condition and still having any kind of liver condition. Having at least one of the above con ditions for the narrow definition was defined based on the seven (7) conditions listed. For “broad” definition: conditions were defined identically except diabetes was defined as self -reported diabetes, fasting plasma glucose ≥126 mg/dL, or hemoglobin A1c ≥6. 5% \nwithout complication; chronic kidney disease was defined as estimated glomerular filtration rate (eGFR) ˂60 (stages 3,4, or 5); and cancer or malignancy in past 2 years was added. This was defined as self -reporting having \"ever been told by a doctor or other health profession that you had cancer or a malignancy of any kind\" and reporting age at diagnosis i n years as being within 2 \nyears of current age in years. As participant age and age at diagnosis for cancer or malignancy are top -coded for ages 80 years and above, those who are aged 80 years and above and report having diagnosis at age 78 years or above are coded as having can cer or malignancy in the past 2 years; this results in an inflated estimate. Of those with any history of cancer or malignancy ag es \n50–79 years, 18.6% had a diagnosis within the past 2 years. Of those with any history of cancer or malignancy ages 80 years and above, 36.0% had a diagnosis at ≥ age 78 years. Having at least one of the above conditions for the broad definition was defi ned  based on the eight (8) conditions listed. Among the fasting sample, ~94% had complete data for all reported medical \nconditions, ~6% were missing data for one (1) medical condition, <1% were missing data for two (2) medical conditions, and no ne were missing data for three (3) or more medical conditions. Estimates of having ≥1 condition are weighted using fasting sampl e weight.  313945 435771\n0102030405060708090100\n50–59 years 60–74 years 75 years and olderPrevalence of at least one chronic \nmedical condition (%)\n105Per 1 Million Vaccine Doses Administered to Adults Aged 60 –74 Years \nWithout  Select Chronic Medical Conditions4:\n1. Range of outcomes avertable was calculated using published 95% confidence interval (outpatient only) and adjusted 95% confide nce interval of RSV -associated incidence of the outcome in RSV -NET\n2. FDA self -controlled case series analysis, among CMS Medicare beneficiaries ≥65 with Parts A, B, and D coverage who did not have a GBS claim in the 365 days before vaccination. Analysis based on \ndiagnoses of GBS in inpatient claims data in risk interval (1 -42 days after RSV vaccination) compared to control interval (43 -90 days after RSV vaccination). GBS cases identified using ICD -10 diagnosis of \nGBS in primary position of inpatient claims coding. Estimates adjusted for outcome -dependent observation time, positive predicti ve value of diagnostic codes in identifying chart -confirmed GBS cases, and \nseasonality. Analysis includes patients with RSV vaccinations  only through October 8, 2023 to allow for 90 -day post -vaccination  observation and 90% or greater claims data completeness. Claims data \nthrough April 6, 2024. \n3. Although CMS data were limited to Medicare beneficiaries aged ≥65 years, results are extrapolated here to include adults aged  60-64 years.\n4. Without chronic obstructive pulmonary disease, asthma, coronary artery disease, diabetes mellitus, chronic kidney disease, an d severe obesity (body mass index ≥40 kg/m2)\n5. Self -controlled case series analysis estimated attributable risk of 3 (95% CI: -3, 10) GBS cases. However, the range was truncat ed at zero for Benefit/Risk analyses.Estimated RSV -Associated Outcomes1 Preventable over 2 RSV Seasons  vs. potential cases of GBS\n(positive predictive value -adjusted  attributable risk of GBS in FDA -CMS partnership data among adults \naged ≥65 years, 42 -day risk interval2,3) \n40 70 500 \n -  1,000  2,000  3,000  4,000  5,000  6,000  7,00040 60 400 \n -  1,000  2,000  3,000  4,000  5,000  6,000  7,000Hospitalizations\nICU Admissions\nDeathsAREXVY (GSK) ABRYSVO (Pfizer)\n3 (range 0–10)5 attributable  cases of GBS 16 (range 3–29) attributable cases of GBS(20–70) (10–60)(30–110) (40–110)(200 –700) (200 –700)\n106GSK AREXVY Pfizer ABRYSVO Moderna mRESVIA\n10-pack of single -dose kits Supplied as single dose, or as a 5 -\npack of single -dose kitsSupplied as single dose pre -filled \nsyringe or 10 -pack\nReconstitution required: single \ndose vial of lyophilized powder \n(antigen component) + single dose \nvial of liquid (adjuvant component) Reconstitution required: single \ndose vial of lyophilized powder \n(antigen component) + single dose \nvial OR prefilled syringe with \nsterile water diluentNo reconstitution required\nBoth components should be \nrefrigerated (2 to 8 °C) in original \ncontainer, protected from lightProduct should be refrigerated (2 \nto 8 °C) in original container, \nprotected from light Store frozen ( -40 to -15°C), may be \nstored refrigerated (2 to 8 °C) for up \nto 30 days prior to use, protected \nfrom light\nAfter reconstitution, the product \nshould be administered within 4 \nhours , otherwise discarded After reconstitution, the product \nshould be administered within 4 \nhours , otherwise discardedThe pre -filled syringes may be \nstored at room temperature (8 to \n25°C) for a total of 24 hours  after \nremoval from refrigerated \nconditions, otherwise discardStorage & handling requirements “back -up slide not shown at meeting”\n107Moderna thawing conditions and times “back -up slide not shown at meeting”\nmRESVIA  Prescribing Information: https://www.fda.gov/media/179005/download\n\n108\nBack -Up Slides: GRADE \n109Outcome Importance Data SourcesEffect Estimate,\nVaccine Efficacya (95% CI)Concerns in certainty \nassessment\nRSV Lower Respiratory Tract \nDisease (LRTD)b,c Important Two Phase 3 randomized \ncontrolled trials (RCT) in adults \n≥60 years1,2\n• Pfizer RCT: Mean efficacy \nfollow up through 16 months  \npost -vaccination per \nparticipant (median 17)\n• GSK RCT: Mean efficacy \nfollow up through 19 months  \npost -vaccination per \nparticipant (median 23)69.4% (36.6, 85.3) None\nMedically attended RSV LRTDb,dCritical 76.6% (58.5, 86.8) Indirectness (serious)e\nHospitalization for RSV \nrespiratory illnessf Critical 75.7% ( -12.5, 94.8)Indirectness (serious)e\nImprecision (serious)g\nSevere RSV respiratory illness \nrequiring O2/respiratory supportfImportant 62.7% ( -88.7, 92.6)Inconsistency (serious)h\nIndirectness (serious)e\nImprecision (serious)g\nDeath due to RSV respiratory \nillnessf Important Zero events observed Unable to evaluateProtein subunit RSV vaccines in adults aged ≥75 years\nBenefits: vaccine efficacy estimates “back -up slide not shown at meeting”\na) Calculated as (1 – Incidence Rate Ratio) in meta -analyses using data provided by manufacturers. Events were included if they occ urred >14 days post -vaccination.\nb) Case definitions differed across RCTs. Pfizer RCT included co -primary outcomes of lower respiratory tract illness (LRTI) with ≥2 or ≥3 lower respiratory signs/symptoms . Data included are for 3 -symptom LRTI. GSK RCT \nincluded a single primary outcome of LRTD.\nc) Included data are from participants aged ≥75 years. \nd) Included data are from Pfizer RCT participants aged ≥75 years, and among all GSK RCT participants (aged ≥60 years).\ne) Serious concern for indirectness due to inclusion of adults aged 60 –74 years.\nf) Included data are from all participants (aged ≥60 years) from both RCTs. Data from GSK include only a mean follow up time of 15 months per participant (median 18 months).\ng) Serious concern for imprecision due to the confidence intervals containing absolute risk reduction estimates for which differ ent policy decisions might be considered.\nh) Serious concern for inconsistency because the point estimates between the studies differed substantially, although the confid ence intervals overlapped\n1. Papi  A, et al. Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older Adults. NEJM 2023; 388:595 –608 https://doi.org/10.1056/NEJMoa2209604  and Ison MG, Papi  A, Athan  E, et al. Efficacy and Safety of \nRespiratory Syncytial Virus (RSV) Prefusion F Protein Vaccine (RSVPreF3 OA) in Older Adults Over 2 RSV Seasons. CID. 2024; on line ahead of print https://doi.org/10.1093/cid/ciae010   plus additional data obtained \ndirectly from the manufacturer\n2. Walsh EE, et al. Efficacy and Safety of a Bivalent RSV Prefusion F Vaccine in Older Adults. NEJM 2023. 388(16): 1465 -1477. https://doi.org/10.1056/NEJMoa2213836  plus additional data obtained directly from the \nmanufacturer \n110Protein subunit RSV vaccines in adults aged ≥75 years\nHarms “back -up slide not shown at meeting”\na) Pooled relative risk estimates were calculated in meta -analyses using data provided by manufacturers.\nb) Included data are from all participants from all trials (aged ≥60 years).\nc) Within 6 months after vaccination\nd) Serious concern for indirectness due to inclusion of adults aged 60 –74 years.\ne) Within 42 days after vaccination\nf) Very serious concern for imprecision due to the width of the confidence interval containing estimates for which different pol icy decisions might be considered and fragility in the estimate.\ng) Pfizer RCTs: within 7 days after vaccination. GSK phase 3 RCT: within 4 days after vaccination. GSK phase 1/2 RCT: within 7 d ays after vaccination.\nh) Inconsistency noted due to I2 value of observed trial outcomes 58%, but this was expected due to differing reactogenicity results for each vaccine observed  in post -licensure data.\ni) Serious concern for imprecision due to the width of the confidence interval containing estimates for which different policy de cisions might be considered\n1. Papi  A, Ison MG, Langley JM, et al. Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older Adults. NEJM. 2023; 388:595 –608 https://doi.org/10.1056/NEJMoa2209604  plus additional data \nobtained directly from the manufacturer\n2. Walsh EE, Pérez Marc G, Zareba AM, et al. Efficacy and Safety of a Bivalent RSV Prefusion F Vaccine in Older Adults. 2023. 38 8(16): 1465 -1477. https://doi.org/10.1056/NEJMoa2213836  plus \nadditional data obtained directly from the manufacturer\n3. Leroux -Roels  I, David MG, Steenackers  K, et al. Safety and Immunogenicity of a Respiratory Syncytial Virus Prefusion F (RSVPreF3) Candidate Vaccine in Older Adults : Phase 1/2 Randomized Clinical \nTrial, The Journal of Infectious Diseases, Volume 227, Issue 6, 15 March 2023, Pages 761 –772, https://doi.org/10.1093/infdis/jiac327  plus additional data obtained directly from the manufacturer\n4. Falsey  AR, Walsh EE, Scott DA, et al. Phase 1/2 Randomized Study of the Immunogenicity, Safety, and Tolerability of a Respiratory Sy ncytial Virus Prefusion F Vaccine in Adults with Concomitant \nInactivated Influenza Vaccine. The Journal of Infectious Diseases. 225(12): 2056 -2066. https://doi.org/10.1093/infdis/jiab611   plus additional data obtained directly from the manufacturerOutcome Importance Data SourcesEffect Estimate,\nRelative riska (95% CI)Concerns in certainty assessment\nSerious adverse events \n(SAEs)b,c Critical\nTwo phase 3 RCTs1,2\nTwo phase 1/2 RCTs3,41.01 (0.93, 1.10) Indirectness (serious)d\nInflammatory \nneurologic eventsb,e Critical 1.76 (0.29, 10.77)Indirectness (serious)d\nImprecision (very serious)f\nReactogenicity (grade \n≥3)b,g Important 1.92 (0.78, 4.70)Indirectness (serious)d\nInconsistency (not serious)h\nImprecision (serious)i\n111Outcome Importance Data SourcesEffect Estimate,\nVaccine Efficacya (95% CI)Concerns in certainty \nassessment\nRSV Lower Respiratory Tract Disease \n(L TRD)b,c ImportantTwo phase 3 randomized \ncontrolled trials (RCT) in adults \n≥60 years1,2\n• Pfizer RCT: Mean efficacy \nfollow up through 16 months  \npost -vaccination per \nparticipant (median 17)\n• GSK RCT: Mean efficacy \nfollow up through 19 months  \npost -vaccination per \nparticipant (median 23)73.1% (58.7, 82.4) None\nMedically attended RSV LRTDb,cCritical 72.7% (52.9, 84.2) None\nHospitalization for RSV respiratory \nillnessd Critical 75.7% ( -12.5, 94.8)Indirectness (serious)e\nImprecision (serious)f\nSevere RSV respiratory illness \nrequiring O2/respiratory supportd Important 62.7% ( -88.7, 92.6)Indirectness (serious)e\nImprecision (serious)f\nInconsistency (serious)g\nDeath due to RSV respiratory illnessdImportant Zero events observed Unable to evaluateRSV protein subunit vaccines in adults aged 60 –74 years at increased risk of severe RSV disease\nBenefits: vaccine efficacy estimates “back -up slide not shown at meeting”\na) Calculated as (1 – Incidence Rate Ratio) in meta -analyses using data provided by manufacturers. Events were included if they occ urred >14 days post -vaccination.\nb) Case definitions differed across RCTs. Pfizer RCT included co -primary outcomes of lower respiratory tract illness (LRTI) with ≥2 or ≥3 lower respiratory signs/symptoms . Data included are for 3 -symptom LRTI. \nGSK RCT included a single primary outcome of LRTD.\nc) Included data are from participants aged 60 –74 years with ≥1 comorbidity (GSK: Pre -existing comorbidities of interest includes C OPD, Asthma, Any chronic respiratory/pulmonary disease, Chronic heart failure, \nDiabetes mellitus Type 1 or Type 2, Advanced liver or renal disease) (Pfizer: Current tobacco use, diabetes, lung disease [in cluding COPD], heart disease [including congestive heart failure], liver disease, renal \ndisease)\nd) Included data are from all participants (aged ≥60 years) from both RCTs. Data from GSK include only a mean follow up time of 15 months per participant (median 18 months).\ne) Serious concern for indirectness due to inclusion of adults without chronic medical conditions.\nf) Serious concern for imprecision due to the confidence intervals containing absolute risk reduction estimates for which differ ent policy decisions might be considered.\ng) Serious concern for inconsistency because the point estimates between the studies differed substantially, although the confid ence intervals overlapped\n1. Papi  A, et al. Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older Adults. NEJM 2023; 388:595 –608 https://doi.org/10.1056/NEJMoa2209604  and Ison MG, Papi  A, Athan  E, et al. Efficacy and Safety of \nRespiratory Syncytial Virus (RSV) Prefusion F Protein Vaccine (RSVPreF3 OA) in Older Adults Over 2 RSV Seasons. CID. 2024; on line ahead of print https://doi.org/10.1093/cid/ciae010   plus additional data obtained \ndirectly from the manufacturer\n2. Walsh EE, et al. Efficacy and Safety of a Bivalent RSV Prefusion F Vaccine in Older Adults. NEJM 2023. 388(16): 1465 -1477. https://doi.org/10.1056/NEJMoa2213836  plus additional data obtained directly from \nthe manufacturer \n112a) Pooled relative risk estimates were calculated in meta -analyses using data provided by manufacturers.\nb) Included data are from all participants (aged ≥60 years).\nc) Within 6 months after vaccination\nd) Serious concern for indirectness due to inclusion of adults aged 60 –74 years.\ne) Within 42 days after vaccination\nf) Very serious concern for imprecision due to the width of the confidence interval containing estimates for which different pol icy decisions might be considered and fragility in the estimate.\ng) Pfizer RCTs: within 7 days after vaccination. GSK phase 3 RCT: within 4 days after vaccination. GSK phase 1/2 RCT: within 7 d ays after vaccination.\nh) Serious concern for imprecision due to the width of the confidence interval containing estimates for which different policy d ecisions might be considered.\ni) Inconsistency noted due to I2 value of observed trial outcomes 58%, but this was expected due to differing reactogenicity results for each vaccine observed  in post -licensure data.\n1. Papi  A, et al. Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older Adults. NEJM 2023; 388:595 –608 https://doi.org/10.1056/NEJMoa2209604  and Ison MG, Papi  A, Athan  E, et al. \nEfficacy and Safety of Respiratory Syncytial Virus (RSV) Prefusion F Protein Vaccine (RSVPreF3 OA) in Older Adults Over 2 RSV  Seasons. CID. 2024; online ahead of print \nhttps://doi.org/10.1093/cid/ciae010   plus additional data obtained directly from the manufacturer\n2. Walsh EE, Pérez Marc G, Zareba AM, et al. Efficacy and Safety of a Bivalent RSV Prefusion F Vaccine in Older Adults. 2023. 38 8(16): 1465 -1477. https://doi.org/10.1056/NEJMoa2213836  plus \nadditional data obtained directly from the manufacturer\n3. Leroux -Roels  I, David MG, Steenackers  K, et al. Safety and Immunogenicity of a Respiratory Syncytial Virus Prefusion F (RSVPreF3) Candidate Vaccine in Older Adults : Phase 1/2 Randomized \nClinical Trial, The Journal of Infectious Diseases, Volume 227, Issue 6, 15 March 2023, Pages 761 –772, https://doi.org/10.1093/infdis/jiac327  plus additional data obtained directly from the \nmanufacturer\n4. Falsey  AR, Walsh EE, Scott DA, et al. Phase 1/2 Randomized Study of the Immunogenicity, Safety, and Tolerability of a Respiratory Sy ncytial Virus Prefusion F Vaccine in Adults with Concomitant \nInactivated Influenza Vaccine. The Journal of Infectious Diseases. 225(12): 2056 -2066. https://doi.org/10.1093/infdis/jiab611   plus additional data obtained directly from the manufacturerOutcome Importance Data SourcesEffect Estimate, Relative Risk \n(95% CI)aConcerns in certainty \nassessment\nSerious adverse \nevents (SAEs)b,cCriticalTwo phase 3 RCT1,2\ntwo phase 1/2 RCT3,4 1.01 (0.93, 1.10) Indirectness (serious)d\nInflammatory \nneurologic eventsb,eCriticalTwo phase 3 RCT1,2\ntwo phase 1/2 RCT3,4 1.76 (0.29, 10.77)Indirectness (serious)d\nImprecision (very serious)f\nReactogenicity \n(grade ≥3)b,gImportantTwo phase 3 RCT1,2\ntwo phase 1/2 RCT3,4 1.92 (0.78, 4.70)Indirectness (serious)d\nImprecision (serious)h\nInconsistency (not serious)iRSV protein subunit vaccines in adults aged 60 –74 years at increased risk of severe RSV disease\nHarms “back -up slide not shown at meeting”\n113Outcome Importance Data SourcesEffect Estimate,\nGeometric mean titer ratioEffect estimate, \nefficacya (95% CI)\nin adults aged ≥60 yearsConcerns in certainty \nassessment\nRSV Lower Respiratory \nTract Disease (L TRD)Important\nOne phase 3 \nRCT in adults \naged 50 –59 \nand ≥60 years1\nOne phase 3 \nRCT in adults \naged ≥60 \nyears2Adults 50 –59 at increased risk \nvs. adults ≥60:\nRSV -A: 1.20 (95% CI: 1.05, 1.37)b\nRSV -B: 1.25 (95% CI: 1.10, 1.41)b73.3% (60.7, 82.3)\nAssessed using mean 19 mo. follow upIndirectness (serious)c\nMedically attended RSV \nLRTDCritical 77.6% (58.3, 88.9)\nAssessed using mean 19 mo. follow upIndirectness (serious)c\nHospitalization for RSV \nrespiratory illnessCritical 76.4% ( -102.3, 97.2)\nAssessed using mean 15 mo. follow upIndirectness (serious)c\nImprecision (very serious)d\nSevere RSV respiratory \nillness requiring \nO2/respiratory supportImportant76.4% ( -102.3, 97.2)\nAssessed using mean 15 mo. follow upIndirectness (serious)c\nImprecision (very serious)d\nDeath due to RSV \nrespiratory illnessImportant Zero events observed Unable to evaluate\na) Calculated as (1 – Incidence Rate Ratio) using data provided by manufacturer. Events were included if they occurred >14 days pos t-vaccination.\nb) Titers assessed through neutralization assay on Day 31, where Day 1 was day of vaccination. \nc) Serious concern for indirectness as the outcome was evaluated using immunobridging  data as a surrogate for vaccine efficacy and there is no established  correlate of protection\nd) Very serious concern for imprecision due to the vaccine efficacy estimate confidence interval in adults 60 and older containi ng estimates for which different policy decisions might be considered, and \nfor fragility of the estimate.\n1. https://clinicaltrials.gov/study/NCT05590403 , https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2023 -10-25-26/02 -gerber -adult -RSV -508.pdf , unpublished data provided by manufacturer\n2. Papi  A, et al. Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older Adults. NEJM 2023; 388:595 –608 https://doi.org/10.1056/NEJMoa2209604 , Ison MG, Papi  A, Athan  E, et al. Efficacy and \nSafety of Respiratory Syncytial Virus (RSV) Prefusion F Protein Vaccine (RSVPreF3 OA) in Older Adults Over 2 RSV Seasons. CID . 2024; online ahead of print https://doi.org/10.1093/cid/ciae010  , \nadditional data obtained directly from the manufacturerGSK AREXVY vaccine in adults aged 50 –59 years at increased risk of severe RSV disease \nBenefits: immunobridging “back -up slide not shown at meeting”\n114a) Within 6 months after vaccination\nb) Serious concern for impression due to the width of the confidence interval containing estimates for which different policy de cisions might be \nconsidered\nc) Serious concern for indirectness due to inclusion of adults without chronic conditions that increase the risk of severe RSV d isease.\nd) Within 42 days after vaccination\ne) Within 4 days after vaccination\n1.https://clinicaltrials.gov/study/NCT05590403 , https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2023 -10-25-26/02 -\ngerber -adult -RSV -508.pdf , unpublished data provided by manufacturerOutcome Importance Data SourcesEffect Estimate, \nrelative risk (95% CI)Concerns in certainty \nassessment\nSerious adverse events (SAEs)a Critical\nOne phase 3 RCT11.12 (0.43, 2.55)Imprecision (serious)b\nIndirectness (serious)c\nInflammatory neurologic eventsd Critical Zero events observed Unable to evaluate\nReactogenicity (grade ≥3)e Important 2.81 (1.45, 5.45) Indirectness (serious)cGSK AREXVY vaccine in adults aged 50 –59 years at increased risk of severe RSV disease\nHarms “back -up slide not shown at meeting”", "summary": "1 Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. Evidence to Recommendations Framework (EtR): RSV Vaccination in Adults Aged 50 –59 years, 60 –74 years,  and 75 years and older Amadea Britton, MD, Co -Lead Adult RSV…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/11-RSV-Adult-Melgar-Roper-Britton-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 114}
{"title": "12 RSV Adult Melgar 508", "content": "1\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nACIP Adult RSV Work Group Clinical Considerations\nRespiratory Syncytial Virus (RSV) in Adults 60 and older \nMichael Melgar, MD\nAmadea Britton, MD\nCo-Leads, Adult RSV Vaccine Work Group \nCoronavirus and Other Respiratory Viruses Division (CORVD)\nAdvisory Committee on Immunization Practices (ACIP)\nJune 26, 2024\n2▪Transition from the current shared clinical decision -making recommendation\n▪Adults aged 60 –74 years at increased risk of severe RSV disease\n▪Timing of RSV vaccination for the 2024 –2025 RSV season\n▪Coadministration of RSV vaccines with other vaccinesOverview\n3\nTransition from the current shared clinical \ndecision -making (SCDM) recommendation\n4▪All adults aged 75 years and older should receive a single \ndose of RSV vaccination . \n▪All adults aged 60–74 years with certain chronic medical \nconditions or other factors that increase risk of severe RSV \ndisease should receive a single dose of RSV vaccination .\n▪These recommendations would replace the SCDM \nrecommendation, meaning that adults aged 60 –74 years \nwithout risk factors for severe RSV disease, are no longer \nrecommended to receive RSV vaccination. Work Group recommends a transition away from shared \nclinical decision -making (SCDM). What does this mean? \n5\nAdults aged 60 –74 years at increased \nrisk of severe RSV disease\n6Chronic medical conditions associated with increased \nrisk of severe RSV disease\nLung disease\nCardiovascular disease\nModerate or severe  immune compromise\nDiabetes Mellitus with end -organ damage\nOther chronic medical conditions that a \nhealthcare provider determines increases risk \nof severe disease due to respiratory infection Neurologic or neuromuscular conditions\nChronic kidney disease, advanced\nHematologic disorders\nLiver disorders\n6Severe  obesity\n(body mass index ≥40 kg/m2) \n\n7Other chronic medical conditions that a \nhealthcare provider determines increases risk \nof severe disease due to respiratory infection While recommendation is intended to be broad enough to implement, note that less \nsevere stages of Diabetes mellitus, Obesity, and Chronic Kidney Disease are excluded \ngiven limited evidence of association with severe RSV disease. \nLung disease\nCardiovascular disease\nModerate or severe  immune compromise\nDiabetes Mellitus with end -organ damageNeurologic or neuromuscular conditions\nChronic kidney disease, advanced\nHematologic disorders\nLiver disorders\nSevere  obesity\n(body mass index ≥40 kg/m2) \n\n8•Chronic cardiovascular disease (e.g., heart failure, \ncoronary artery disease, congenital heart disease; \nexcluding isolated hypertension )\n•Chronic lung disease (e.g., chronic obstructive \npulmonary disease [COPD], emphysema, asthma, \ninterstitial lung disease, cystic fibrosis)\n•Chronic kidney disease, advanced (e.g., stages 4 –5, \ndependence on hemodialysis or other renal \nreplacement therapy)\n•Diabetes mellitus with end -organ damage (e.g., \ndiabetic nephropathy, neuropathy, retinopathy, or \ncardiovascular disease)\n•Severe obesity (body mass index ≥40 kg/m2)\n•Decreased immune function from disease or drugs \n(i.e., immunocompromising conditions *)•Neurologic or neuromuscular conditions (e.g., \nneuromuscular conditions causing impaired airway \nclearance or respiratory muscle weakness; excluding \nhistory of stroke without impaired airway clearance )\n•Liver disorders (e.g., cirrhosis)\n•Hematologic conditions (e.g., sickle cell disease, \nthalassemia)\n•Frailty \n•Residence in a nursing home or other long -term \ncare facility \n•Other chronic medical conditions or risk factors \nthat a health care provider determines would \nincrease the risk of severe disease due to \nrespiratory infectionChronic medical conditions and risk factors for a risk -based recommendation for RSV \nvaccination in adults aged 60 –74 years\n*List of immunocompromising conditions would match the existing list from the COVID -19 vaccination Interim Clinical Consideratio ns: \nhttps://www.cdc.gov/vaccines/covid -19/clinical -considerations/interim -considerations -us.html#immunocompromised  \n9Other factors associated with increased risk of \nsevere RSV disease\nResidence in a nursing home or other long -term care \nfacility (L TCF)*\nFrailty\nOther factors determined to increase risk of severe disease due to \nrespiratory infection \n*Long -term care facilities do NOT include retirement communities or senior independent living communities in which residents are  able to perform activities of \ndaily living without assistance.\n10\nOther considerations\n11▪RSV vaccination should be given \nONL Y to adults who have not yet \nreceived a dose of RSV vaccine. \n▪At this time, it is anticipated that \nadults may need additional doses of \nRSV vaccine in the future, but ideal \nrevaccination timing is not yet \nknown. Adults who have already \nreceived a dose of RSV vaccine \nDO NOT need to receive \nanother dose this year. RSV vaccination will have the \nmost benefit if given in late \nsummer or early fall .\n▪This means from August to \nOctober in most of the United \nStates.\n▪Note this is not a formal \nseasonal recommendation for \nRSV vaccination. Older adults \nmay continue to receive RSV \nvaccination year -round.\n12In accordance with General Best Practice Guidelines for \nImmunization, coadministration of RSV vaccines with other \nadult vaccines is acceptable.*\n*ACIP Timing and Spacing Guidelines for Immunization | CDC  This includes giving RSV vaccines simultaneously with \nseasonal influenza vaccines, COVID -19 vaccines, \npneumococcal vaccines, Td/Tdap, and recombinant zoster \nvaccine (Shingrix) .Co-administration of RSV vaccines and other vaccines\n13\nFor more information, contact CDC\n1-800 -CDC -INFO (232 -4636)\nTTY:  1 -888 -232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention.\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.", "summary": "1 Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. ACIP Adult RSV Work Group Clinical Considerations Respiratory Syncytial Virus (RSV) in Adults 60 and older  Michael Melgar, MD Amadea Britton, MD Co-Leads, Adult RSV…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/12-RSV-Adult-Melgar-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 13}
{"title": "01 Vaxelis Loehr 508", "content": "Introduction to Session: \nCombined Diphtheria and Tetanus Toxoids and Acellular \nPertussis, Inactivated Poliovirus, Haemophilus influenzae \nType b Conjugate, and Hepatitis B vaccine (Vaxelis) \nJamie Loehr, MD\nChair, ACIP Hib/Meningococcal Vaccines Work Group\nJune 26, 2024National Center for Immunization & Respiratory Diseases\n1\nACIP Meningococcal/Hib Vaccines Work Group\n▪ ACIP Members on the WG\n•Jamie Loehr (Chair)\n•Wilbur Chen\n▪ Ex Officio WG Members\n•Margaret Bash (FDA)\n•Matthew Clark (IHS)\n•Xin-Xing Gu (NIH)\n▪ WG Liaisons and Consultants\n•Amra Resic  (AAFP)\n•Mary Healy (AAP) \n•Barb Fluty (ACHA)\n•Karyn Lyons (AIM)\n•Paul Cieslak (CSTE)\n•Kathy Hsu (IDSA)\n•Pamela Doyon -Plourde (NACI)\n•Jeff Goad (NFID)\n•Jessica Cataldi (PIDS)\n•Amy Middleman (SAHM)\n•Kathy Poehling (Wake Forest)\n•Lynn Bahta (Minnesota Department of Health)\n•David Stephens (Emory)\n▪ GRADE/ EtR Support\n•Doug Campos -Outcalt (Arizona)\n•Rebecca Morgan (Case Western Reserve)▪ CDC Contributors\n•Jennifer Collins (DBD/NCIRD)\n•Sarah Schillie (DBD/NCIRD)\n•Lucy McNamara (DBD/NCIRD)\n•LeAnne Fox (DBD/NCIRD)\n•Susan Hariri (DBD/NCIRD)\n•Amy Rubis (DBD/NCIRD)\n•Gabrielle Cooper (DBD/NCIRD)\n•Noele Nelson (DBD/NCIRD)\n•Alison Albert (DBD/NCIRD)\n•Shelby Miller (DBD/NCIRD)\n•Marc Fischer (DIDRI/NCEZID)\n•Xiaoyu Dong (ISD/NCIRD)\n•Andrew Leidner (ISD/NCIRD)\n•Ismael Ortega -Sanchez (CORVD/NCIRD)\n•Jonathan Duffy (DHQP/NCEZID)\n•Pedro Moro (DHQP/NCEZID)\n•Tanya Myers (DHQP/NCEZID) \n•Liz Velazquez (ISD/NCIRD)\n•Jessica MacNeil (ACIP Secretariat)\n•Hannah Rosenblum (ACIP Secretariat)\n•Melinda Wharton (ACIP Secretariat)\n2\nBackground\n▪PRP-OMP ( PedvaxHIB ) is preferentially recommended for American \nIndian and Alaska Native (AI/AN) infants\n•It provides a protective antibody response after the first dose\n•Historically, Hib meningitis peaked at an earlier age among AI/AN \ninfants\n▪Vaxelis (DTaP -IPV-Hib-HepB ) does not currently have a preferential \nrecommendation for AI/AN infants because\n•It contains PRP -OMP in a lower amount than PedvaxHIB\n•Post -dose 1 immunogenicity data were not previously available\n3\nThe use of trade names is for identification purposes only and does not imply endorsement by CDC.\nPolicy question\nShould DTaP-IPV-Hib-HepB (Vaxelis) be included with \nPRP-OMP (PedvaxHIB) in the preferential \nrecommendation for American Indian and Alaska Native \n(AI/AN) infants based on the Hib component?\n4\nThe use of trade names is for identification purposes only and does not imply endorsement by CDC.\nFebruary 2024 ACIP Meeting Presentations\n▪Epidemiology of invasive Hib disease in AI/AN populations and \nevidence supporting the existing preferential recommendation for \nPedvaxHIB\n▪Clinical trial data on post -dose 1 immunogenicity of Vaxelis vs. \nPedvaxHIB\n▪Preliminary Work Group considerations\n5\nThe use of trade names is for identification purposes only and does not imply endorsement by CDC.\n6Today’s agenda\nAll topics will be presented for information, discussion, and voteTopic Presenter\nEvidence to Recommendations and \nProposed Recommendations: Use of \nVaxelis among American Indian and \nAlaska Native Infants Dr. Jennifer Collins (CDC/NCIRD)\nUpdated Vaccines for Children (VFC) \nResolutionDr. Jeanne Santoli (CDC/NCIRD)\nThe use of trade names is for identification purposes only and does not imply endorsement by CDC.", "summary": "Introduction to Session:  Combined Diphtheria and Tetanus Toxoids and Acellular  Pertussis, Inactivated Poliovirus, Haemophilus influenzae  Type b Conjugate, and Hepatitis B vaccine (Vaxelis)  Jamie Loehr, MD Chair, ACIP Hib/Meningococcal Vaccines Work Group June 26, 2024National Center for Immunization & Respiratory Diseases 1 ACIP Meningococcal/Hib Vaccines Work Group ▪ ACIP Members on the WG •Jamie Loehr (Chair) •Wilbur Chen ▪ Ex Officio WG Members •Margaret Bash (FDA) •Matthew Clark (IHS)…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/01-Vaxelis-Loehr-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 6}
{"title": "02 Vaxelis Collins 508", "content": "Evidence to Recommendations and Proposed \nRecommendations: Use of Vaxelis among \nAmerican Indian and Alaska Native Infants\nJennifer Collins, MD, MSc\nCo-Lead, ACIP Hib/Meningococcal Vaccines Work Group\nJune 26, 2024National Center for Immunization & Respiratory Diseases\n\n2▪Capsular polysaccharide (PRP) conjugated to carrier proteins\n–Tetanus toxoid (PRP -T)\n–Outer membrane protein of meningococcal serogroup B (PRP -OMP)\n▪Highly immunogenic via activation of T -cell dependent immunity\n–95% of infants develop protective antibody levels after a primary series\n–Estimated clinical efficacy 95% ─100% \n–Invasive Hib disease is uncommon in children who are fully vaccinated Haemophilus influenzae type b (Hib) \npolysaccharide conjugate vaccines remain \nthe primary prevention strategy for Hib disease\n2\n3Current Hib vaccines in the United States\nVaccine Product Trade Name Primary series Booster dose\nMonovalent vaccines\nPRP-OMP PedvaxHIB * 2, 4 months 12–15 months\nPRP-T ActHIB 2, 4, 6 months 12–15 months\nPRP-T Hiberix 2, 4, 6 months 12–15 months\nCombination vaccines**\nDTaP -IPV/Hib Pentacel 2, 4, 6 months 12–15 months\nDTaP -IPV-Hib-HepB Vaxelis 2, 4, 6 months ***\n*Recommended vaccine for American Indian/Alaska Native children\n**Hib component of Pentacel  is PRP -T. Hib component of Vaxelis is PRP -OMP .\n***Vaxelis is not recommended for the booster dose. A different Hib -containing vaccine should be administered as a booster at 12 –15 months. 3\nThe use of trade names is for identification purposes only and does not imply endorsement by CDC.\nBriere EC, et al. Prevention and Control of Haemophilus influenzae Type b Disease: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR \nRecommendations and Reports . 63(RR01);1- 14\nThe use of trade names is for identification purposes only and does not imply endorsement by CDC.PedvaxHIB (PRP-OMP) is preferentially recommended \nfor AI/AN infants\n•Vaccination with a 2 dose primary series of a Hib vaccine that contains \nPRP-OMP ( PedvaxHIB ) is preferred for AI/AN infants to provide early \nprotection because this vaccine produce a protective antibody response \nafter the first dose\n•A booster dose (dose 3) of Hib vaccine is recommended at age 12 \nthrough 15 months; for the booster dose, there is no preferred vaccine \nformulation\n4\n5Vaxelis (DTaP- IPV-Hib-HepB) does not \ncurrently have a preferential recommendation \nfor AI/AN infants\nVaccine Product Trade Name PRP OMP\nPRP-OMP PedvaxHIB 7.5 mcg 125 mcg\nDTaP -IPV-Hib-HepB Vaxelis 3 mcg 50 mcg▪Post -dose 1 immunogenicity data not previously available\n▪Lower dose of PRP -OMP than PedvaxHIB\n5\nThe use of trade names is for identification purposes only and does not imply endorsement by CDC.\n6Policy question\nShould DTaP-IPV-Hib-HepB (Vaxelis) be included with \nPRP-OMP (PedvaxHIB) in the preferential \nrecommendation for American Indian and Alaska Native \n(AI/AN) infants based on the Hib component?\nThe use of trade names is for identification purposes only and does not imply endorsement by CDC.\nPublic health problem\nIs invasive Hib disease among American Indian and Alaska Native infants a \nproblem of public health importance?\n8•Before the introduction of effective vaccines, Hib was the leading cause \nof bacterial meningitis and other invasive bacterial disease in the United \nStates, primarily among children aged <5 years\n•Most common clinical syndromes of invasive Hib disease in the post -\nvaccine eraPublic health problem\nBacteremic \npneumonia\nMeningitisBacteremia \nwithout a focus\n\n9▪Incidence of invasive Hib disease\ndeclined >99% with introduction of\nHib vaccines\n▪American Indian/Alaska Native\nchildren aged <5 years have a 31 -\nfold higher incidence of invasive Hib\ndisease than non -Native childrenIncidence per 100,000 of invasive Hib disease \namong children aged <5 years, 2011 –2020 \n0123\nAI/AN Non-AI/AN2.5\n0.08051015202530\n1980 1990 2000 2010Incidence per 100,000 of invasive Hib disease \namong children aged <5 years, 1980 –2012Public health problem\n10▪Is invasive Hib disease a public health problem among American Indian \nand Alaska Native populations?Public health problem:\nWork Group determination\nNo Probably no Probably yes Yes Varies Don’t know\nMost common  2nd most common \nBenefits and harms\n- How substantial are the desirable anticipated effects?\n- How substantial are the undesirable anticipated effects?\n- Do the desirable effects outweigh the undesirable effects?\n12PICO components\nPopulation American Indian and Alaska Native infants\nIntervention Vaxelis (DTaP -IPV-Hib-HepB )\nComparison PedvaxHIB  (PRP -OMP)\nOutcomes- Invasive Hib disease\n- Post -dose 1 immunity\n- Post -primary series immunity\n- Serious adverse events\nThe use of trade names is for identification purposes only and does not imply endorsement by CDC.\n13GRADE evidence retrieval\nRecords identified and\nscreened\n(n=2,332) \nRecords excluded based on title (n=2,290):\nNot a Hib vaccine clinical trial (n=2,070)\nDifferent Hib vaccine (n=191)\nDid not enroll AI/AN infants (n=29)Abstracts assessed for \neligibility\n(n=42) Records excluded based on abstract/full text (n=41):\nNot a Hib vaccine clinical trial (n=6)\nDifferent Hib vaccine (n=10)\nDid not enroll AI/AN infants (n=16)\nOther PICO components not aligned (n=9) Articles included in GRADE\n(n=1)\n*Search was limited to studies in English from 2014 –present based on earliest clinical trials of Vaxelis having been published in 2015. Two reviewers screened titles, abstracts and full-text records, \nas indicated, to determine whether records should be included.\nThe use of trade names is for identification purposes only and does not imply endorsement by CDC.\n14GRADE Table 2: Outcomes and Rankings\nOutcome ImportanceIncluded in \nevidence profile\nInvasive Hib disease Important No\nPost -dose 1 immunity Critical Yes\nPost -primary series immunity Important Yes\nSerious adverse events Critical Yes\n15▪Immunity and serious adverse events assessed using data from one phase \nIV, prospective, open -label randomized controlled clinical trial \n–Enrolled healthy infants\n•Born at gestational age ≥35 weeks\n•Aged 42 –90 days at the time of first vaccination\n•Identified as AI/AN by parent/legally authorized representative\n–Randomized to Vaxelis vs. PedvaxHIB\n•Vaxelis administered at ages 2, 4, and 6 months\n•PedvaxHIB  administered at ages 2 and 4 months\n–Compared antibody levels before vaccination vs. day 30, 120, and 150 post -\ndose 1\n–Safety monitoring for serious adverse events on day 0, 30, 60, 120, and 150  Available evidence\nThe use of trade names is for identification purposes only and does not imply endorsement by CDC.\n16Post-dose 1 immunity \n▪Anti-Hib IgG geometric mean \nconcentration (GMC) ratio (Vaxelis: \nPedvaxHIB ) 30 days post -dose 1 \nmet pre -specified non -inferiority \ncriterion \n▪The proportion of infants with anti -\nHib concentration above the \nputative correlate of short -term \nprotection 30 days post -dose 1 was \nsimilar between groups\n–Vaxelis 75.7%\n–PedvaxHIB  71.2%Slide credits: Laura Hammitt’s  February 2024 ACIP Presentation\nThe use of trade names is for identification purposes only and does not imply endorsement by CDC.\n17GRADE evidence profile: post-dose 1 immunity\nAssessed via proportion with anti- Hib IgG concentration ≥0.15 µg/mL 30 days post -dose 1\nCertainty assessment Summary of findings Importance\n#\nstudiesStudy \ndesignRisk of \nbiasInconsistency Indirectness Imprecision Other \nconsiderations# patients Effect Certainty\nVaxelis\nn/N\n%\n(95% CI)PedvaxHIB\nn/N\n%\n(95% CI)Relative \nrisk \n(95% \nCI)Absolute risk\n(95% CI)\n1 RCTNot \nseriousaNot \nseriousNot seriousb,c,dSeriouse None 115/152\n(75.7%)104/146\n(71.2%)1.06 \n(0.93 –\n1.22)4,274 more \nper 100,000 \n(from 4,986 \nfewer to \n15,671 more)Moderate Critical\na Similar loss to follow -up for anti -Hib IgG concentration 30 days post -dose 1: Vaxelis: 15/167 (9%), PedvaxHIB : 20/166 (12%), p=0.36. Open -label study design would not affect \nimmune response. Median time of post -dose 1 blood draw was similar between groups: Vaxelis 34 days (IQR 32 –37 days) versus PedvaxHIB  34 days (IQR 31 –39 days).\nb Immunity is inferred from proportion with anti -Hib concentration above the putative correlate of short -term protection. \nC As modeled by constrained longitudinal data analysis, anti -Hib GMC 30 days post -dose 1 for Vaxelis group (0.41; 95% CI: 0.33 –0.51) was non -inferior to that of the PedvaxHIB  \ngroup (0.40; 95% CI: 0.31 –0.50). Ratio of GMCs ( Vaxelis:PedvaxHIB ): 1.03 (95% CI: 0.75 –1.41); the pre -specified non -inferiority criterion was met based on the lower bound of \nthe 95% CI being >0.67.\nd Study was conducted among Navajo Nation and Alaska Native infants and may not be generalizable to other American Indian popul ations; WG members determined this did \nnot warrant a downgrade.\ne Downgraded because the absolute effect confidence interval is wide.\n The use of trade names is for identification purposes only and does not imply endorsement by CDC.\n18▪The proportion of infants with \nanti-Hib concentration above the \nputative correlate of long -term \nprotection 150 days post -dose 1 \nwas higher in the Vaxelis group \n(83.6%) than in the PedvaxHIB  \ngroup (71.7%, p<0.05) \n▪Antibody titers were not \ncollected beyond day 150 post -\ndose 1Post-primary series immunity \nSlide credit: Laura Hammitt’s  February 2024 ACIP Presentation\nThe use of trade names is for identification purposes only and does not imply endorsement by CDC.\n19GRADE evidence profile: post-primary series immunity\nAssessed via proportion with anti- Hib IgG concentration ≥1.0 µg/mL 150 days post -dose 1\nCertainty assessment Summary of findings Importance\n#\nstudiesStudy \ndesignRisk of \nbiasInconsistency Indirectness Imprecision Other \nconsiderations# patients Effect Certainty\nVaxelis\nn/N\n%\n(95% CI)PedvaxHIB\nn/N\n%\n(95% CI)Relative \nrisk \n(95% \nCI)Absolute \nrisk\n(95% CI)\n1 RCTNot \nseriousaNot \nseriousNot seriousb,cSeriousd None 107/128\n(83.6%)84/117 \n(71.8%) 1.16 \n(1.02 –\n1.34) 11,487 more \nper 100,000 \n(from 1,436 \nmore to \n24,410 \nmore)Moderate Important\na Similar loss to follow -up for anti -Hib IgG concentration 150 days post -dose 1: Vaxelis 39/167 (23%), PedvaxHIB  49/166 (30%), p=0.20. Open -label study design would not \naffect immune response. Median time of day 150 blood draw was similar between groups: Vaxelis 174 days (IQR 163 –187 days) versus PedvaxHIB  180 days (IQR 162 –189 \ndays).\nb Immunity is inferred from proportion with anti -Hib concentration above the putative correlate of long -term protection.\nc Study was conducted among Navajo Nation and Alaska Native infants and may not be generalizable to other American Indian popul ations; WG members determined this did \nnot warrant a downgrade.\nd Downgraded because the absolute effect confidence interval is wide.\n \nThe use of trade names is for identification purposes only and does not imply endorsement by CDC.\n20General safety of Vaxelis (DTaP-IPV-Hib-HepB) \n▪In pre -licensure clinical trials, the safety profile was consistent with that of \nlicensed comparator vaccines except higher rate of fever than with DTaP -IPV/Hib \n(Pentacel ) (47.1% –47.4% vs. 33.2% –34.4%)1,2; rates of fever -related medical \nevents were similar between groups\n▪Post -licensure analysis of Vaccine Adverse Event Reporting System ( VAERS) data \nfrom June 26, 2019 – June 16, 2023 did not identify new or unexpected safety \nissues\n1Marshall GS, et al. Immunogenicity, safety and tolerability of a hexavalent vaccine in infants. Pediatrics 2015;136:e323 –32.\n2Block SL, et al. Lot -to-lot consistency, safety, tolerability and immunogenicity of an investigational hexavalent vaccine in U.S . infants. Pediatr  Infect Dis J 2017;36:202 –8.\nThe use of trade names is for identification purposes only and does not imply endorsement by CDC.\n21▪The frequency of SAEs was similar \nbetween groups\n–Vaxelis (5%)\n–PedvaxHIB  (7%)\n▪The most common SAE was acute \nrespiratory infection \n▪No SAEs were deemed related to \nstudy participation GRADE: Serious adverse events among \nAI/AN infants in the Hibvax Study\nSlide credit: Laura Hammitt’s  February 2024 ACIP Presentation\nThe use of trade names is for identification purposes only and does not imply endorsement by CDC.\n22GRADE evidence profile: serious adverse events\nAssessed via proportion with SAEsa\nCertainty assessment Summary of findings Importance\n#\nstudiesStudy \ndesignRisk of \nbiasInconsistency Indirectness Imprecision Other \nconsiderations# patients Effect Certainty\nVaxelis\nn/N\n%\n(95% CI)PedvaxHIB\nn/N\n%\n(95% CI)Relative \nrisk \n(95% \nCI)Absolute \nrisk\n(95% CI)\n1 RCTNot \nseriousbNot \nseriousNot seriouscSeriousd None9/167 \n(5.4%) e12/166 \n(7.2%)e0.75 \n(0.32 –\n1.72)1,807 \nfewer per \n100,000 \n(from \n4,916 \nfewer to \n5,205 \nmore)Moderate Critical\na From the time of the first dose of study vaccine to the end of the last study visit (approximately 5 months).\nb Similar loss to follow -up through the last study visit: Vaxelis 21/166 (13%) PedvaxHIB  16/167 (10%)  p=0.37. Open -label study design may bias reporting of SAEs but WG members \ndetermined this did not warrant a downgrade. \nc Study was conducted among Navajo Nation and Alaska Native infants and may not be generalizable to other American Indian popul ations; WG members determined this did not \nwarrant a downgrade.\nd Downgraded because the absolute effect confidence interval is wide.\ne In the Vaxelis group 10 SAEs occurred among 9 participants. In the PedvaxHIB group, 15 SAEs occurred among 12 participants. The most common SAE was acute respiratory infection \n21/25 (84%). No SAEs were deemed related to study participation. \n The use of trade names is for identification purposes only and does not imply endorsement by CDC.\n23GRADE Summary Table\nType Outcome ImportanceDesign \n(# studies)FindingsEvidence \ntype*\nBenefitsInvasive Hib disease n/a No data available ND\nPost -dose 1 \nimmunityCritical RCT (1)The proportion participants with anti -Hib \nconcentration ≥0.15 µg/mL* 30 days post -dose 1 \nwas similar between groupsModerate\nPost -primary series \nimmunityImportant RCT (1)The proportion participants with anti -Hib \nconcentration ≥1.0 µg/mL** 150 days post -dose 1 \nwas higher in the Vaxelis group. Antibody titers \nwere not available beyond day 150 post -dose 1.Moderate\nHarmsSerious adverse \neventsCritical RCT (1)The proportion of SAEs was similar between \ngroups; no SAEs were deemed related to study \nparticipationModerate\n*Putative correlate of short -term protection\n**Putative correlate of long -term protection\nThe use of trade names is for identification purposes only and does not imply endorsement by CDC.\n24▪How substantial are the desirable anticipated effects overall and for each \nmain outcome for which there is a desirable effect?\n▪How substantial are the undesirable effects overall and for each main \noutcome for which there is an undesirable effect?Benefits and harms:\nWork Group determination\nMinimal Small Moderate Large Varies Don’t know\nMost common    2nd most common           3rd most common                  MajorityMinimal Small Moderate Large Varies Don’t know\n25▪Do the desirable effects outweigh the undesirable effects?\n▪What is the overall certainty of evidence for the critical outcomes?Benefits and harms:\nWork Group determination\nMost common  2nd most common        Majority Favors \nintervention \n(Vaxelis only)Favors\ncomparison \n(PedvaxHIB  only)Favors \nboth \n(Vaxelis & PedvaxHIB )Favors \nneitherUnclear\nHigh Moderate Low Very low\nThe use of trade names is for identification purposes only and does not imply endorsement by CDC.\nValues\n- Does the target population feel that the desirable effects are large relative to \nthe undesirable effects?\n- Is there important uncertainty about or variability in how much people value \nthe main outcome?\n27▪Limited data were available\n▪Vaxelis would provide an additional option for AI/AN infants\n▪In collaboration with CDC’ Office of Tribal Affairs and Strategic Alliances \n(OTASA), NCIRD held a listening session with tribal communities in January \n2024\n–80 attendees, including\n•9 from tribes or tribal serving organizations\n•46 from Indian Health Service (IHS)\n–Key questions and concerns raised by participants for WG consideration\n•Will Vaxelis offer the same protection as PedvaxHIB ?\n•Need to monitor for possible breakthrough cases\n•Safety and side effects  Values\nThe use of trade names is for identification purposes only and does not imply endorsement by CDC.\n28▪Does the target population feel the desirable effects are large relative to \nthe undesirable effects?\n▪Is there important uncertainty about, or variability in, how patients value \nthe outcomes?Values:\nWork Group determination\nNo Probably no Probably yes Yes Varies Don’t know\nNo Probably no Probably yes Yes Varies Don’t know\nMost common   2nd most common          3rd most common   4th most common                     Majority\nAcceptability\nIs the intervention acceptable to key stakeholders?\n30▪Limited data were available\n▪Vaxelis would reduce the number of injections to complete the childhood \nimmunization series for those who receive it and may therefore improve \nacceptability for parents/guardians and medical providers\n▪CDC’s General Best Practice Guidance for Immunization and American \nAcademy of Pediatrics Red Book  both state a general preference for \ncombination vaccines over separate injections of equivalent component \nvaccines1,2\n–Considerations should include provider assessment, patient preference, \nand the potential for adverse events.1\n▪Proposed policy option to add Vaxelis retains flexibility for providers to \ncontinue using PedvaxHIBAcceptability \n1General Best Practice Guidelines for Immunization. Best Practice Guidance of the ACIP. https://www.cdc.gov/vaccines/hcp/acip -recs/general -recs/index.html    \n2American Academy of Pediatrics. Red Book 2018 Report of the Committee on Infectious Diseases. 31st Edition.\nThe use of trade names is for identification purposes only and does not imply endorsement by CDC.\n31General best practice guidance for \nimmunization: combination vaccines \nPotential advantages Potential disadvantages\n•Improved vaccine coverage rates\n•Timely catch -up immunizations\n•Reduced shipping and stocking costs\n•Reduced costs for extra health care visits necessitated by \ndeferral of vaccination\n•Facilitation of additional new vaccines into vaccination \nprograms•Adverse events that might occur more frequently with \ncombination vaccines than with individual components\n•Confusion and uncertainty about selection of vaccine \ncombinations and schedules for subsequent doses \n•Extra doses of certain antigens in the combination product\n1General Best Practice Guidelines for Immunization. Best Practice Guidance of the ACIP. https://www.cdc.gov/vaccines/hcp/acip -recs/general -recs/index.html    \n32▪Is the intervention acceptable to key stakeholders?\n–Are there key stakeholders that would not accept the distribution of \nbenefits, harms, and costs?\n–Are there key stakeholders that would not accept the costs or \nundesirable effects in the short term for the desirable effects in the \nfuture?Acceptability:\nWork Group determination\nNo Probably no Probably yes Yes Varies Don’t know\nMost common   2nd most common          3rd most common                  Majority\nResource use\n- Is the intervention a reasonable and efficient allocation of resources?\n34Vaxelis protects against 6 infections with fewer \ninjections\nPediarix  is a combination vaccine that protects against diphtheria, tetanus, pertussis, polio, and hepatitis B.\nDTaP is a vaccine that protects against diphtheria, tetanus, and pertussis. The 4th dose of DTaP is recommended at age 15 –18 months.\nIPV is inactivated polio vaccine.Option 2 months 4 months 6 months 12–15 \nmonthsTotal shots\n1 Vaxelis Vaxelis Vaxelis PedvaxHIB\nDTaP5\n2 PedvaxHIB\nPediarixPedvaxHIB\nPediarix PediarixPedvaxHIB\nDTaP7\n3 PedvaxHIB\nDTaP\nIPV\nHepBPedvaxHIB\nDTaP\nIPVDTaP\nIPV\nHepBPedvaxHIB\nDTaP12\nThe use of trade names is for identification purposes only and does not imply endorsement by CDC.\n35Pediatric/Vaccines for Children (VFC) Vaccine Price List\nPediarix  is a combination vaccine that protects against diphtheria, tetanus, pertussis, polio, and hepatitis B.\nDTaP is a vaccine that protects against diphtheria, tetanus, and pertussis. \nIPV is inactivated polio vaccine.Vaccine Trade name CDC cost/dose Private sector \ncost/dose\nDTaP -IPV-Hib-HepB Vaxelis $100.59 $150.85\nPRP-OMP PedvaxHIB $16.14 $29.71\nDTaP -HepB -IPV Pediarix $66.07 $97.97\nDTaPDaptacel $21.69 $29.31\nInfanrix $21.66 $28.80\nIPV IPOL $16.46 $42.64\nHepBEngerix  B $17.38 $28.42\nRecombivax  HB $14.59 $27.12\nThe use of trade names is for identification purposes only and does not imply endorsement by CDC.\n36Estimated cost of vaccine options that protect against \nthe 6 pathogens in Vaxelis\n*Vaccine cost ranges reflect different costs for DTaP ( Daptacel  vs. Infanrix) and HepB  (Engerix  B vs. Recombivax  HB). \n**Assumptions: private sector administration cost $34.53 for first vaccine based on estimates from a 2014 study, adjusted for  inflation.1 A factor of 0.6 was used to calculate the p rivate  sector \nadministration cost of $20.72 for subsequent doses at the same visit based a 2019 study.2 Public sector administration costs were assumed to be half of private sector costs.3\n1Tsai Y et al. Prev Med Rep. 2019 Jun 7:15:100917. doi: 10.1016/j.pmedr.2019.100917 \n2Tsai Y et al. .Am J Prev Med. 2019 Aug;57(2):180 -190. doi: 10.1016/j.amepre.2019.03.011 \n3Tsai Y. Med Care. 2018 Jan; 56(1): 54 –61.OptionVaccines \n(# doses to complete \nchildhood series)Total CDC cost \n(vaccines only*)Total CDC cost \n(vaccines + admin**)Total private sector cost \n(vaccines only*)Total private sector cost \n(vaccines + admin**)\n1Vaxelis (3)\n$339.57 –339.60 $419.01 –419.04 $511.06 –511.57 $669.90 –670.41 PedvaxHIB  (1)\nDTaP (1)\n2Pediarix  (3)\n$268.29 –268.32 $368.45 –368.48 $411.84 –412.35 $612.12 –612.63 PedvaxHIB  (3)\nDTaP (1)\n3PedvaxHIB  (3)\n$213.62 –219.32 $365.58 –371.28 $386.49 –391.13 $690.37 –695.01DTaP (4)\nIPV (3)\nHepB  (2)\nThe use of trade names is for identification purposes only and does not imply endorsement by CDC.\n37OptionVaccines \n(# doses to complete \nchildhood series)Total CDC cost \n(vaccines only*)Total CDC cost \n(vaccines + admin**)Total private sector cost \n(vaccines only*)Total private sector cost \n(vaccines + admin**)\n1Vaxelis (3)\n$339.57 –339.60 $419.01 –419.04 $511.06 –511.57 $669.90 –670.41 PedvaxHIB  (1)\nDTaP (1)\n2Pediarix  (3)\n$268.29 –268.32 $368.45 –368.48 $411.84 –412.35 $612.12 –612.63 PedvaxHIB  (3)\nDTaP (1)\n3PedvaxHIB  (3)\n$213.62 –219.32 $365.58 –371.28 $386.49 –391.13 $690.37 –695.01DTaP (4)\nIPV (3)\nHepB  (2)Vaccine only costs are higher for option 1 \n(i.e., using Vaxelis)\n*Vaccine cost ranges reflect different costs for DTaP ( Daptacel  vs. Infanrix) and HepB  (Engerix  B vs. Recombivax  HB). \n**Assumptions: private sector administration cost $34.53 for first vaccine based on estimates from a 2014 study, adjusted for  inflation.1 A factor of 0.6 was used to calculate the p rivate  sector \nadministration cost of $20.72 for subsequent doses at the same visit based a 2019 study.2 Public sector administration costs were assumed to be half of private sector costs.3\n1Tsai Y et al. Prev Med Rep. 2019 Jun 7:15:100917. doi: 10.1016/j.pmedr.2019.100917 \n2Tsai Y et al. .Am J Prev Med. 2019 Aug;57(2):180 -190. doi: 10.1016/j.amepre.2019.03.011 \n3Tsai Y. Med Care. 2018 Jan; 56(1): 54 –61.\nThe use of trade names is for identification purposes only and does not imply endorsement by CDC.\n38OptionVaccines \n(# doses to complete \nchildhood series)Total CDC cost \n(vaccines only*)Total CDC cost \n(vaccines + admin**)Total private sector cost \n(vaccines only*)Total private sector cost \n(vaccines + admin**)\n1Vaxelis (3)\n$339.57 –339.60 $419.01 –419.04 $511.06 –511.57 $669.90 –670.41 PedvaxHIB  (1)\nDTaP (1)\n2Pediarix  (3)\n$268.29 –268.32 $368.45 –368.48 $411.84 –412.35 $612.12 –612.63 PedvaxHIB  (3)\nDTaP (1)\n3PedvaxHIB  (3)\n$213.62 –219.32 $365.58 –371.28 $386.49 –391.13 $690.37 –695.01DTaP (4)\nIPV (3)\nHepB  (2)Total costs are similar accounting for administration \ncosts\n*Vaccine cost ranges reflect different costs for DTaP ( Daptacel  vs. Infanrix) and HepB  (Engerix  B vs. Recombivax  HB). \n**Assumptions: private sector administration cost $34.53 for first vaccine based on estimates from a 2014 study, adjusted for  inflation.1 A factor of 0.6 was used to calculate the p rivate  sector \nadministration cost of $20.72 for subsequent doses at the same visit based a 2019 study.2 Public sector administration costs were assumed to be half of private sector costs.3\n1Tsai Y et al. Prev Med Rep. 2019 Jun 7:15:100917. doi: 10.1016/j.pmedr.2019.100917 \n2Tsai Y et al. .Am J Prev Med. 2019 Aug;57(2):180 -190. doi: 10.1016/j.amepre.2019.03.011 \n3Tsai Y. Med Care. 2018 Jan; 56(1): 54 –61.\nThe use of trade names is for identification purposes only and does not imply endorsement by CDC.\n39▪Cost is similar for Vaxelis and other vaccine options that cover the same \npathogens, accounting for administration costs\n▪Resource use has been acceptable for the general U.S. population; \nequitable to use the same standard for AI/AN childrenResource use (summary)\nThe use of trade names is for identification purposes only and does not imply endorsement by CDC.\n40▪Is using Vaxelis among American Indian and Alaska Native infants a \nreasonable and efficient allocation of resources?Resource use:\nWork Group determination\nNo Probably no Probably yes Yes Varies Don’t know\nThe use of trade names is for identification purposes only and does not imply endorsement by CDC.Most common   2nd most common          3rd most common                 Majority\nEquity\n- What would be the impact on health equity?\n42▪Limited data were available\n▪The option to use a combination vaccine may improve equity by\n–Improving reliability of the vaccine supply\n–Improving Hib vaccination uptake among AI/AN populations, who \nare disproportionately at risk for invasive Hib diseaseEquity\nThe use of trade names is for identification purposes only and does not imply endorsement by CDC.\n43▪What would be the impact of using Vaxelis among American Indian and \nAlaska Native infants on health equity? Equity:\nWork Group determination\nMinimal* Small Moderate Large** Varies Don’t know\n*Would not reduce disparities\n**Would greatly reduce disparities\nMost common   2nd most common          3rd most common   4th most common                     Majority\nThe use of trade names is for identification purposes only and does not imply endorsement by CDC.\nFeasibility\n- Is the intervention feasible to implement?\n45▪Widely used in the general U.S. population with >7.4 million doses distributed in the United \nStates (as of Q1 2024)1\n▪Adding Vaxelis to the preferential recommendation for AI/AN infants would\n–Increase flexibility for patients and providers\n–Reduce the number of injections to complete the childhood immunization series for those who \nreceive it\n▪Neither Vaxelis nor PedvaxHIB  require reconstitution\n▪Shelf life of Vaxelis (4 years) is longer than that of PedvaxHIB  (3 years)\n▪Vaxelis cannot be used for the booster dose; clinics will need to stock additional products\n–Stocking PRP -OMP ( PedvaxHIB ) for the Hib booster dose would maintain parent/guardian and \nprovider flexibility to choose this for doses 1 –3 \n–Stocking PRP -T is also an option\n•Vaxelis primary series with a heterologous booster (PRP -T) was shown to produce a robust \nimmune response in a small study2\n•Risk of inadvertent administration of PRP -T for doses 1 –3 with a less robust immune \nresponse following doses 1 and 2Feasibility\n1Per the manufacturer  \n2Wilck et al. Vaccine . 2021;39(9):1428- 1434.  \nThe use of trade names is for identification purposes only and does not imply endorsement by CDC.\n46▪Is using Vaxelis among American Indian and Alaska Native infants feasible \nto implement?Feasibility:\nWork Group determination\nNo Probably no Probably yes Yes Varies Don’t know\nThe use of trade names is for identification purposes only and does not imply endorsement by CDC.Most common  2nd most common        Majority \nSummary\n \nEtR Domain Question Work group \ndetermination\nPublic health problem Is invasive Hib disease among American Indian and Alaska Native children a problem of \npublic health importance?Yes\nBenefits and harms How substantial are the desirable anticipated effects? Moderate\nHow substantial are the undesirable anticipated effects? Minimal\nDo the desirable anticipated effects outweigh the undesirable effects? Favors both \n(Vaxelis & PedvaxHIB )\nWhat is the overall certainty of the evidence for the critical outcomes? Moderate\nValues Does the target population feel the desirable effects are large relative to the undesirable \neffects?Probably yes or yes\nIs there important variability in how patients value the outcome? Probably no, probably \nyes or don’t know\nAcceptability Is the intervention acceptable to key stakeholders? Probably yes\nResource use Is the intervention a reasonable and efficient allocation of resources? Yes\nEquity What would be the impact of the intervention on health equity? Moderate\nFeasibility Is the intervention feasible to implement? Yes\n48The use of trade names is for identification purposes only and does not imply endorsement by CDC.Favorable             Uncertain \n49Balance of Consequences\nUndesirable \nconsequences  \nclearly outweigh  \ndesirable \nconsequences in \nmost settings Undesirable \nconsequences \nprobably \noutweigh \ndesirable \nconsequences in \nmost settingsThe balance \nbetween  \ndesirable and \nundesirable \nconsequences is \nclosely balanced \nor uncertain Desirable \nconsequences  \nprobably \noutweigh \nundesirable \nconsequences in \nmost settingsDesirable \nconsequences \nclearly outweigh \nundesirable \nconsequences in \nmost settingsThere is \ninsufficient \nevidence to \ndetermine the \nbalance of \nconsequences\nMost common   2nd most common  Majority of WG members think desirable consequences probably \noutweigh undesirable consequences in most settings\nIs there sufficient information to move forward with a recommendation?\nYes No\n49\n50Most common  2nd most common Work Group Interpretation:\nShould DTaP-IPV-Hib-HepB (Vaxelis) be included with PRP-OMP \n(PedvaxHIB) in the preferential recommendation for American \nIndian and Alaska Native infants based on the Hib component?\nWe do not recommend the intervention\nWe recommend the intervention\nMajority of WG members favored recommending the intervention\n \n50The use of trade names is for identification purposes only and does not imply endorsement by CDC.\n51ACIP recommends DTaP-IPV-Hib-HepB (Vaxelis®) should be included with \nPRP-OMP (PedvaxHIB®) in the preferential recommendation for American \nIndian and Alaska Native infants based on the Haemophilus influenzae \ntype b (Hib) Hib component.Draft proposal language\n51The use of trade names is for identification purposes only and does not imply endorsement by CDC.\nAcknowledgments\n▪ ACIP Members on the WG\n– Jamie Loehr (Chair)\n– Wilbur Chen\n▪ Ex Officio WG Members\n– Margaret Bash (FDA)\n– Matthew Clark (IHS)\n– Xin-Xing Gu (NIH)\n▪ WG Liaisons and Consultants\n– Amra Resic  (AAFP)\n– Mary Healy (AAP) \n– Barb Fluty (ACHA)\n– Karyn Lyons (AIM)\n– Paul Cieslak (CSTE)\n– Kathy Hsu (IDSA)\n– Pamela Doyon -Plourde (NACI)\n– Jeff Goad (NFID)\n– Jessica Cataldi (PIDS)\n– Amy Middleman (SAHM)\n– Kathy Poehling (Wake Forest)\n– Lynn Bahta (Minnesota Department of Health)\n– David Stephens (Emory)▪ CDC Contributors\n– Lucy McNamara (DBD/NCIRD)\n– Sarah Schillie (DBD/NCIRD)\n– LeAnne Fox (DBD/NCIRD)\n– Susan Hariri (DBD/NCIRD)\n– Veronica Pinell -McNamara (DBD/NCIRD)\n– Amy Rubis (DBD/NCIRD)\n– Gabrielle Cooper (DBD/NCIRD)\n– Noele Nelson (DBD/NCIRD)\n– Alison Albert (DBD/NCIRD)\n– Angela Jiles (DBD/NCIRD)\n– Shelby Miller (DBD/NCIRD)\n– Marc Fischer (DIDRI/NCEZID)\n– Jonathan Duffy (DHQP/NCEZID)\n– Pedro Moro (DHQP/NCEZID)\n– Tanya Myers (DHQP/NCEZID) \n– Liz Velazquez (ISD/NCIRD)\n– Jessica MacNeil (ACIP Secretariat)\n– Hannah Rosenblum (ACIP Secretariat)\n– Melinda Wharton (ACIP Secretariat)\n▪ GRADE/ EtR Support\n– Doug Campos -Outcalt (Arizona)\n– Rebecca Morgan (Case Western Reserve) 52\nThank you!\nFor more information, contact CDC\n1-800-CDC-INFO (232-4636)\nTTY:  1- 888- 232-6348    cdc.gov\nFollow us on X (Twitter) @CDCgov & @CDCEnvironment\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position o f \nthe U. S. Centers for Disease Control and Prevention.\n53", "summary": "Evidence to Recommendations and Proposed  Recommendations: Use of Vaxelis among  American Indian and Alaska Native Infants Jennifer Collins, MD, MSc Co-Lead, ACIP Hib/Meningococcal Vaccines Work Group June 26, 2024National Center for Immunization & Respiratory Diseases  2▪Capsular polysaccharide (PRP) conjugated to carrier proteins –Tetanus toxoid (PRP -T) –Outer membrane protein of meningococcal serogroup B (PRP -OMP) ▪Highly immunogenic via activation of T -cell dependent immunity –95% of…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/02-Vaxelis-Collins-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 53}
{"title": "03 POLIO Kidd 508", "content": "Centers for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation use. No rights  are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.Clinical Considerations for Children who Received \nFractional Dose Inactivated Polio Vaccine ( fIPV ) in \nOther Countries\nSarah Kidd, MD, MPH\nACIP Meeting\nFebruary 28, 2024\n\n▪Wild poliovirus type 2 eradicated in 2015\n▪Global switch and withdrawal of Sabin type 2 virus from OPV in April 2016: \n–Replaced all trivalent OPV ( tOPV ; types 1, 2, and 3) with bivalent OPV ( bOPV ; types 1 and 3)\n–≥1 dose IPV recommended as part of routine immunization in all countries using bOPV\n▪Based on clinical trial data and limited IPV availability, WHO supports use of 2 \nfractional doses of IPV (1/5 full dose IPV) given intradermally in place of single full \nIPV dose (intramuscular)Background\nWHO. World Epidemiological Record 2016;91:561 –82. \nWHO. World Epidemiological Record 2021;96:613 –32.\nhttps://www.who.int/teams/immunization -vaccines -and-biologicals/diseases/poliomyelitis -(polio)  \nONE fractional IPV ( fIPV ) dose is LESS immunogenic than \none full IPV dose\nMeta -analysis of percent that seroconverted for poliovirus type 2 ( Mashunye  2021)\nMashunye et al. Lancet Infect Dis 2021;21:1161 –74.\n\nTWO fractional IPV ( fIPV ) doses are MORE immunogenic \nthan one full IPV dose\nSlide adapted from Concepcion Estivariz.\nData from Snider et al. Lancet 2019; 393:2624. 0102030405060708090\nType 1 Type 2 Type 3Percent with seroconversion at 18 weeks \n2 fIPV 6 & 14 wk 1 IPV 6 wk 1 IPV 14 wk\n* P< 0.01 versus 2 fIPV doses  **\n**\n* *\n▪6 countries (~20% of global birth cohort) use 2 fIPV doses + ≥3 bOPV  doses in routine \nchildhood immunization schedule\n–Bangladesh, Cuba, Ecuador, India, Nepal, Sri Lanka \nExample polio vaccination schedule (India):Current Use of fIPV  in Routine Immunization Globally\nBirth 6 weeks 10 weeks 14 weeks 16–24 \nmonthsTotal doses\nbOPV X X X X X 5 bOPV\nfIPV X X 2 fIPV\n▪Recommended polio vaccination\n–4 total IPV doses, administered at 2, 4, 6 –18 months, and 4 –6 years OR\n–3 total IPV doses if 3rd dose administered after 4th birthday and ≥6 months after 2nd dose\n▪For vaccines administered outside of US\n–Only tOPV  or IPV doses considered valid for US vaccination schedule\nExample polio vaccination schedule (India):Current US Guidance\nBirth 6 weeks 10 weeks 14 weeks 16–24 \nmonthsTotal \ndoses\nbOPV X X X X X 5 bOPV\nfIPV X X 2 fIPVCurrent US guidance:\n•None of these \ndoses considered \nvalid in US\n•Needs 3 –4 full IPV \ndoses in US\nShould 2 fractional IPV doses administered outside of the United States \nbe counted as either 1 or 2 doses towards the US vaccination schedule?Question for Work Group: \n▪Previous meta -analysis published in 2021 ( Mashunye  et al) \n▪Literature review using same search terms; searched Medline, Embase, Cochrane \nLibrary, Scopus, and ClinicalTrials.gov\n–Randomized clinical trials\n–Compared 2 fIPV doses to either 1 or 2 IPV doses\n–Published between January 1, 2019 and June 30, 2023\n▪Outcomes\n–Seroconversion for poliovirus type 2\n•Change from seronegative (titer <1:8) to seropositive (titer ≥1:8) OR\n•≥4-fold increase in antibody titer over expected decline in maternal antibodies\n–Changes in geometric mean titersMethods: Updated Meta -Analysis\nMashunye et al. Lancet Infect Dis 2021;21:1161 –74.\nSeroconversion: 2 fIPV  Doses vs. 1 IPV Dose\n\nSeroconversion: 2 fIPV  Doses vs. 2 IPV Doses\n\nSeroconversion: 2 fIPV  doses are less favorable vs. 2 IPV \ndoses when given at younger age\n6 and 14 weeks\n2 and 4 months\n10 and 14 weeks\n4 and 8 months\n14 weeks and 36 weeks\n3 and 11 –15 months14 weeks and 9 months4 and 8 months6 and 10 weeksAge\nMedian Antibody Titers Lower After 2 fIPV  vs. 2 IPV Doses\nResik  2010 (3 doses at 6, 10, and 14 weeks)\n Mohammed 2010 (3 doses at 2, 4, and 6 months)\nResik  2020 (2 doses at 4 and 8 months)\nfIPVIPVfIPVIPV\nAge fIPV IPV\nResik  2013 4 and 8 months 898 (713 -≥1448) ≥1448 (≥1448 -≥1448)\nAziz 2022 9-13 and 11 -15 months 455 (362 -724) ≥1448 (1152 -≥1448)Resik  2013 and Aziz 2022: Median titer (95% CI) after 2 doses\nResik  et al, J Infect Dis 2010; Resik  et al, J Infect Dis 2020; Mohammed et al, N Engl J Med 2010; Resik  et al, N Engl J Med 201; Aziz et al, J Infect Dis 2022.\nGeometric Mean Titers: 2 fIPV  vs. 2 IPV Doses\nBandyopadhyay et al. Lancet Infect Dis 2021;21:559 –68.\n(10-14-36 weeks)\n(14-36 weeks)\n(10-14-36 weeks)\n(14-36 weeks)4 weeks after 2 doses \nIPV vs. 2 doses fIPV  \n(given at 10 and 14 \nweeks)4 weeks after 2 doses \nIPV vs. 2 doses fIPV  \n(given at 14 and 36 \nweeks)\nPersistence of Poliovirus Type 2 Antibodies Following 2 fIPV  \nor 2 IPV Doses\nSaleem et al. JID 2021; 223(7)1214\nSlide adapted from Concepcion Estivariz.\n•As immunization \nseries with fIPV \nreach lower final \ntiters, seronegativity  \nexpected to be \nreached earlier 2 IPV doses\n2 fIPV  doses\n▪WHO supports the use of 2 fIPV doses in place of 1 IPV dose as an IPV conservation \nstrategy\n▪2 fIPV doses associated with higher  rates of seroconversion vs. 1 IPV dose\n▪2 fIPV doses associated with slightly lower  rates of seroconversion vs. 2 IPV doses\n–Especially when administered at 6 and 14 weeks; rates of seroconversion approach equivalency at older ages \nof administration\n▪Peak antibody titers are  lower after 2 fIPV doses vs. 2 IPV dosesSummary\n▪For persons who received fractional (1/5 full dose) IPV administered intradermally \noutside of the United States, 2 fractional doses of IPV ( fIPV) should be considered \nvalid and counted as 1 full intramuscular dose of IPV towards the US vaccination \nschedule. \n▪If a person received only 1 dose of fIPV, this dose should not be considered valid or \ncounted towards the US vaccination schedule.Proposed CDC Clinical Considerations\nQuestions and Discussion\n▪ACIP voting members\n–Oliver Brooks (Chair)\n–Lynn Bahta\n–Sybil Cineas\n▪Liaisons\n–Lynn Fisher, American Academy of Family Physicians\n–Chandy C. John, American Academy of Pediatrics \n–Sandra Fryhofer , American Medical Association\n–Kathy Kudish, Association of Immunization Managers\n–Marcus Plescia , Association of State and Territorial Health Officials\n–Paul R. Cieslak , Council of State and Territorial Epidemiologists\n–Christine Hahn, Council of State and Territorial Epidemiologists\n–Tina Q. Tan, Infectious Diseases Society of America\n–Adenike  Shoyinka , Infectious Diseases Society of America\n–Mary Wilson, International Society of Travel Medicine\n–Jaqueline Lawler, National Association of County and City Health Officials\n–Kathy Edwards, Pediatric Infectious Diseases Society\n–Joseline Zafack , Public Health Agency of Canada*Polio Work Group Members\n*In the event of a Work Group poll, CDC, FDA, and Public Health Agency of Canada members are not included.▪Consultants\n–Edwin Asturias\n–Doug E Campos -Outcalt *\n–Emily Lutterloh\n–Jennifer Rosen\n–Eli Rosenberg\n▪FDA*\n–Robin Levis\n▪CDC*\n–Cara Burns\n–Thomas Clark\n–Miranda Delahoy\n–Brian Edlin\n–Concepcion Estivariz\n–Halle Getachew\n–Sarah Kidd\n–Janelle King\n–Adriana Lopez\n–M. Steve Oberste", "summary": "Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-28-29-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-02-28-29/03-POLIO-Kidd-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 18}
{"title": "01 RSV Adults Kotton 508", "content": "Centers for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nAdult Respiratory Syncytial Virus (RSV) Session\nCamille Kotton, MD\nChair, Adult RSV Work Group\nAdvisory Committee on Immunization Practices (ACIP)\nFebruary 29, 2024\nAs a reminder, ACIP recommended that adults aged ≥60 years may \nreceive RSV vaccination, using  shared clinical decision -making.\nThere are currently two licensed and recommended products for adults aged ≥60 years:\n–GSK RSV vaccine (Arexvy ): a 1 -dose adjuvanted (AS01E) recombinant \nprefusion F protein (preF ) vaccine. \n–Pfizer RSV vaccine (Abysvo ): a 1 -dose recombinant preF  vaccine. In June 2023, ACIP made the first -ever recommendation for \nthe use of RSV vaccine in older adults. \nhttps://www.cdc.gov/mmwr/volumes/72/wr/mm7229a4.htm  2\nThe ACIP Adult RSV Work Group shared their early interpretations of \nthese data and the potential role of RSV vaccination in adults younger \nthan 60 years, including subpopulations that would benefit most from \nvaccination and equity implications.\nAt that time ACIP members expressed the importance of reviewing safety surveillance data to inform future preferred policy \nrecommendations . In October 2023, GSK presented data to ACIP demonstrating that the humoral immune response to a single dose of GSK RSV vaccine in adults \n50–59 years is non -inferior to that in adults ages 60 years and older.\n3\nThe Work Group is committed to incorporating what we are learning from \npost -licensure data in a transparent way that ensures safety for the public \nand clarity for providers. \nThe preliminary data shared today are the first in what will be a series of rigorous analyses across multiple different platforms.  \nCDC and the Work Group will be engaged in ongoing re- assessment and \nfuture policy will be responsive to what is learned over the coming \nmonths. At today’s meeting CDC and FDA will be sharing preliminary \ndata from multiple safety surveillance platforms. \n4\nRisk of severe RSV disease in adults ages 50 -59 years, especially those \nwith chronic medical conditions \nRSV vaccine uptake among different demographic groups \nPotential policy options that would transition away from shared clinical \ndecision -making The Work Group has simultaneously been reviewing additional \ndata to prepare for upcoming potential policy decisions. \n5\nWe will open today’s session with a presentation from Moderna, who will be sharing \nsafety and efficacy data with ACIP for the first time from their primary Phase 2 -3 trial \nevaluating mRNA -1345.The Work Group has also begun reviewing data from Moderna on their \ninvestigational RSV vaccine (mRNA- 1345) in adults aged ≥60 years.\n6\nAgenda: February 29, 2024\nManufacturer presentation: Overview of Moderna’s Investigational \nRSV Vaccine (mRNA -1345) in Adults ≥60 Years of Age\nRisk -stratified rates of RSV -associated hospitalization among \nadults\nImplementation update: older adult RSV vaccination\nPost -marketing safety surveillance of older adult RSV vaccination\nPreliminary Analysis of Guillain -Barré Syndrome (GBS) following \nRSV Vaccination among adults 65 years and older\nOlder adult RSV vaccination: benefits and risks discussion\nWork Group interpretations and discussionDr. Rituparna Das (Moderna)\nDr. Rebecca Woodruff (CDC)\nDr. Carla Black (CDC)\nDr. Tom Shimabukuro (CDC)Dr. Patricia Lloyd (FDA)\nDr. Michael Melgar (CDC)\nDr. Amadea Britton (CDC)\n7\nAdult RSV Work Group Membership\n8ACIP Voting Members\nCamille Kotton (Chair)\nKeipp Talbot\nSarah Long\nEx Officio Members\nRachel Zhang (FDA)\nNicholas Geagan (FDA)\nNadine Peart Akindele (FDA)\nSonnie Kim (NIH/NIAID)\nJeffrey Kelman (CMS)Michelle Juaneza (HRSA/VICP )\nUzo Chukwuma (IHS)\nValerie Marshall (OIDP)Consultants\nRobert Atmar (Baylor Coll. of Medicine)\nHelen Chu (U Washington)\nPeter Donofrio (Vanderbilt University)\nMarie Griffin (Vanderbilt University)\nCynthia Lucero -Obusan  (VHA)Tracy Ruckwardt (NIH/NIAID)\nJonathan Temte  (U Wisconsin)\nRebecca Morgan (Case Western)\nDoug C ampos -Outcalt  (U Arizona)\nLiaisons\nKenneth Schmader (AGS)\nVidya Sundareshan (ACP)Gretchen LaSalle (AAFP)April Killikelly (NACI /PHAC)\nWinnie Su (NACI/ PHAC)Katherine Williams (APTR)Ruth Lynfield (NFID)Bindy Crouch (AIM)Steven Pergam (IDSA)Elizabeth Skoy ( APhA)\nCDC Contributors\nAmadea Britton (co -lead)\nMichael Melgar (co -lead)\nLauren Roper\nFiona Havers \nChris TaylorMonica Patton\nRebecca Woodruff\nMeredith McMorrow\nDave Wentworth\nDiya Surie\nJennifer DeCuir\nMila Prill\nMonica GodfreyRuth Link -Gelles\nAmanda Payne\nDanielle Moulia\nMegan Wallace\nNatalie ThornburgMelissa Coughlin\nJefferson Jones\nKatherine Fleming -Dutra\nIsmael Ortega Sanchez\nNoelle Molinari\nPragna Patel\nAron Hall\nHannah RosenblumDerrell Powers\nRaigan Wheeler\nJarrett Gartin\nTrang Nguyen Wisard\nElizabeth Greene\nManisha Patel\nLisa Grohskopf\nAnne HauseDavid Shay\nChristine Olson\nTom Shimabukuro\nKaren Broder\nJohn HsuPedro Moro\nPatricia WodiAndrew Leidner\nJamison Pike\nSarah Meyer\nElisha Hall  \nNicole DowlingTara Anderson\n9\nFor more information, contact CDC\n1-800- CDC- INFO (232 -4636)\nTTY:  1 -888 -232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention.\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.", "summary": "Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. Adult Respiratory Syncytial Virus (RSV) Session Camille Kotton, MD Chair, Adult RSV Work Group Advisory Committee on Immunization Practices (ACIP) February 29, 2024 As a…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-28-29-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-02-28-29/01-RSV-Adults-Kotton-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 10}
{"title": "02 RSV Adults Das 508", "content": "© 2024 Moderna, inc. All rights reserved.Overview of Moderna’s \nInvestigational RSV Vaccine (mRNA-1345) in Adults ≥ 60 Years of Age\nAdvisory Committee on Immunization Practices (ACIP)\nRituparna Das, MD, PhD\nFeb 29, 2024The safety and efficacy of this investigational RSV vaccine have \nnot been established in any country for any use   \nOutline of \nPresentationOverview of mRNA- 1345, Moderna’s \ninvestigational RSV vaccine\nPivotal Phase 2/3 trial\nEfficacy\nSafety\nImmunogenicity\nPersistence of antibody and revaccination – \n Phase 1 trial\nConcomitant administration with influenza and \nCOVID- 19 vaccines\nSummary \nNE-3\nInvestigational RSV Vaccine (mRNA -1345) Designed to Encode \nfor a Stabilized Prefusion F Glycoprotein\n•LNP encapsulated mRNA -based vaccine \nencoding the RSV fusion (F) glycoprotein\nstabilized in the prefusion conformation\n•Prefusion F elicits potent neutralizing \nantibody response1,2\n•Antibodies to the F protein cross -react between RSV -A and RSV -B\n•RSV vaccine uses the same LNP as \nModerna COVID -19 vaccines3\n•Phase 1: mRNA -1345 is well tolerated with \npersistent antibody levels through 12 \nmonths4\n1. Crank et al. Science , 2019;  2. McKekkan et al. Science, 2013; 3. Aranda and Polack, Front Immunol , 2019; 4. Simorellis et al. ESWI  2023 \nNE-4\nPivotal Safety and Efficacy Trial of RSV Vaccine, \nmRNA-1345 (Study 301)\nNE-5\nStudy Design\nPopulation\nHealthy adults including those with chronic, stable medical conditions, and/or frailty \n≥ 60 years of age\n22 countries (both Northern and Southern Hemisphere)\nRegimen and follow -up\nSingle-dose regimen (1:1 50 μg RSV vaccine or saline placebo)\n24-month follow -up\nWeekly active RSV case surveillance performed throughout study to addresses \nunpredictability of RSV seasons following pandemic\nStratified by \nAge (60 - 74 and ≥ 75 years)\nPresence or absence of congestive heart failure or chronic  obstructive pulmonary \ndiseaseStudy 301\nclinicaltrials.gov NCT05127434 https://clinicaltrials.gov/ct2/show/NCT05127434\nNE-6\nEnrollment Enriched for High -Risk Groups\nStudy 301\nCOPD\nCHF\nAsthma\nChronic respiratory disease1 \nDiabetes\nAdvanced liver disease\nAdvanced renal diseaseMeasured by Edmonton Frail Scale across 9 domains: \nCognition\nGeneral health status\nFunctional independence\nSocial support\nMedication use\n0-17 point scale\nFit (0 –3)\nVulnerable (4– 5)\nFrail (6 -17)\nIndividuals with Comorbidities\n Frail Individuals\n1 Chronic respiratory disease includes chronic pulmonary \nfibrosis (idiopathic and otherwise), restrictive lung \ndisease, asbestosis, bronchiectasis, cystic fibrosis, pulmonary hypertension, sarcoidosis, and history of tuberculosisNutrition\nMood\nContinence\nFunctional \nperformance\nNE-7\nStudy Design – Randomization\nStudy 301\nNo safety signals identified after DSMB review of Phase 2 safety data\nAllowed for seamless transition to start of Phase 3Adults \n≥ 60 Years\nN = 36,557 \nClinicaltrials.gov NCT05127434 https://clinicaltrials.gov/ct2/show/NCT05127434\nDSMB = Data Safety and Monitoring Board\nPhase 2\nUnited States\nInitiated November 2021\nN = 1,991\nPhase 3\nGlobal Sites\nInitiated February 2022\nN = 34,566\nInvestigational RSV Vaccine (mRNA -1345, 50 μg)\nN = 993\nPlacebo\nN = 998\nInvestigational RSV Vaccine (mRNA -1345, 50 μg)\nN = 17,311\nPlacebo\nN = 17,2551:1\n1:1\nNE-8\n36,557 Participants Enrolled in 22 Countries \n(as of April 30, 2023 data cutoff)\nStudy 301\nNumber of participants in each country shown in parentheses269 Study Sites Across Northern and Southern Hemisphere\nAustralia  (256) \nBangladesh (2,421)\nJapan  (822) \nNew Zealand  (299)\nSingapore  (8) \nSouth Korea (27)\nTaiwan  (84)\nSouth Africa (982)Belgium  (413)\nFinland (96)\nGermany  (471)\nPoland (346)\nSpain (220)\nUnited Kingdom (450) Canada  (706)\nUnited States  (19,571)\nMexico  (733)\nArgentina  (3,589)\nChile  (679)\nColombia  (2,625)\nCosta Rica (208)\nPanama  (1,551)Randomization Set\nNE-9\nPrimary and Additional Efficacy Analyses\nUS 2021-2023 RSV Hospitalization Rates (RSV -NET) in Adults ≥ 65 Years1\n*Median RSV hospitalization rate for 2016 – 2019. Data only collected from October to April each year. \n1. CDC. Respiratory Syncytial Virus Hospitalization Surveillance Network (RSV -NET). https://data.cdc.gov/Public -Health- Surveilla nce/Weekly -Rates -of-Laboratory -Confirmed -RSV-Hospitali/29hc -\nw46k/data_preview. 2. Wilson E, et al. NEJM. 2023;389:2233- 2244. RSV efficacy study \nconducted across2021 – 2022 and \n2022 – 2023 seasons\n>50% of participants enrolled in US\nPrimary Analysis: Met success criteria\n2\nAdditional Analysis: 94% of participants followed for ≥ 6 monthsOverall RSV \nHospitalization \nRate per \n100,000 Adults \n≥ 65 Years \n01234567\n2016 -2019 \nRSV Seasons*2021 -2022 \nRSV Season 2016 -2019 \nRSV Seasons*Additional  Analysis\nNovember 2021 –  April 2023\nMedian 8.6 Months (range 0.5 – 17.7) Follow -upVaccination Period\nNovember 2021 –  December 2022\nPrimary Analysis\nNovember 2021 –  November 2022\nMedian 3.7 Months (range 0.5 - 12.6) Follow -up\n2022 -2023 \nRSV Season\nNE-10\nDemographics of Study Participants\nCharacteristicRSV Vaccine (mRNA -1345)\n(N = 18,304)Placebo\n(N = 18,253)\nMedian Age, years 67 67\nMale, n (%) 9,376 ( 51%) 9,277 (51%)\nAge Group, n (%)\n60 – 69 Years 11,348 (62%) 11,301 (62%)\n70 – 79 Years 5,512 (30%) 5,500 (30%)\n≥ 80 Years 1,444 (8%) 1,452 (8%)\nRace/Ethnicity, n (%)\nWhite 11,318 (62%) 11,290 (62%)\nBlack or African American 2,210 (12%) 2,175 (12%)\nAsian 2,014 (11%) 2,001 (11%)\nAmerican Indian or Alaska Native 907 (5%) 897 (5%)\nNative Hawaiian or Other Pacific Islander 28 (0.2%) 19 (0.1%)\nHispanic / Latino Ethnicity 6,118 (33%) 6,169 (34%)Study 301\nAge, gender, race, and ethnicity balanced between vaccine and placebo recipients\nRace/ethnicity generally representative of US populationRandomization Set\nNE-11\n1. Chronic respiratory disease includes chronic pulmonary fibrosis (idiopathic and otherwise), restrictive lung disease, asbesto sis, bronchiectasis, cystic fibrosis,\n    pulmonary hypertension, sarcoidosis, and history of tuberculosis \n2. Based on 17- point Edmonton Frailty ScoreParticipants with Lower Respiratory Tract Disease (LRTD) \nRisk Factors and Comorbidities of Interest \nCharacteristicRSV Vaccine (mRNA -1345)\n(N = 18,304)Placebo\n(N =18,253)\nCHF or COPD, n (%) 1,310 (7%) 1,316 (7%)\n≥1 Comorbidity of Interest, n (%)\nCOPD, CHF, asthma, chronic respiratory disease1, \ndiabetes, advanced liver disease, advanced renal disease5,417 (30%) 5,316 (29%)\nFrailty2, n (%)\nVulnerable (score of 4- 5) 2,852 (16%) 2,917 (16%)\nFrail (score of 6- 17) 1,013 (6%) 1,033 (6%)Study 301\nRandomization Set\nEnrollment included those at highest risk of severe RSV\nNE-12\nSafety Data\nStudy 301\nSafety Set –  April 30, 2023 data cutoff\nBased on 6 months of follow -up for ~94% of participants\nNE-13\nPrimary Safety Endpoints and Duration of Follow -up\nStudy 301\n1. Neurologic events of interest include Guillain -Barre syndrome, \nacute disseminated encephalomyelitis, Bell’s palsy, and seizuresActive Safety \nSurveillanceSolicited Local and \nSystemic Adverse \nReactions\nUnsolicited Adverse Events\nMedically Attended AEs, Serious AEs Including Death, AEs Leading to \nDiscontinuations\nAdverse Events of Special Interest(including Myocarditis, Pericarditis, Thrombocytopenia, Neurologic Events\n1, and Anaphylaxis )\n7 Days 28 Days 24 months\n(ongoing)\nNE-14Solicited Local Reactions within 7 Days After RSV Vaccine vs \nPlacebo\nStudy 301 - Solicited Safety Set \n55.9%\n13.8%\n2.0% 0.6%3.7%0.0%15.2%\n6.1%\n0%20%40%60%80%100%Injection \nSite PainInjection Site \nErythemaInjection Site \nSwellingAxillary Swelling \nor Tenderness\n<1%Grade 2\nGrade 3Grade 1\nRSV vaccine, n=18174; placebo, n=18102\nFor placebo, grade 2 erythema and grade 2 and grade 3 swelling were < 1%No grade 4 local adverse reactionsSafety Set\nMostly grade 1, onset day 1-2, median duration of 1 -2 days for RSV vaccinePlacebo RSV Placebo RSV Placebo RSV Placebo RSV\nNE-15Solicited Systemic Reactions within 7 Days After RSV Vaccine vs \nPlacebo\nStudy 301 - Solicited Safety Set \n2.8% 1.3%26.7%\n18.8%30.8%\n20.0%25.6%\n14.4%21.7%\n14.0%\n7.0%5.3%11.6%\n6.8%\n0%20%40%60%80%100%Headache Fatigue Myalgia ArthralgiaNausea / \nVomitingChills Fever\nRSV vaccine, n=18174; placebo, n=18102\nGrade 4 fever was reported (mRNA -1345 [n=29] and placebo [n=35]); no other categories reported any grade 4 reactionsSafety Set\nMostly grade 1, onset day 1-2, median duration of 1 -2 days for RSV vaccineGrade 2\nGrade 3Grade 1\nPlacebo RSV Placebo RSV Placebo RSV Placebo RSV Placebo RSV Placebo RSV Placebo RSV \nNE-16Unsolicited Adverse Events Within 28 Days After Injection, \nRegardless of Relationship to Vaccine/Placebo\nRSV Vaccine (mRNA -1345)\n(N = 18,245)Placebo\n(N = 18,184)\n All, n (%) 3,749 (21%) 3,412 (19%)\nSerious 115 (0.6%) 111(0.6%)\nFatal 1(<0.1%) 6 (<0.1%)\nMedically -Attended 1,606 (9%) 1,531 (8%)\nLeading to Study Discontinuation 2(<0.1%) 11(<0.1%)\nSevere/≥ Grade 3 129(0.7%) 135(0.7%)\nNon- Serious 3,634 (20%) 3,301 (18%)\nAny Adverse Event of Special Interest  (AESI) 3(<0.1%) 8(<0.1%)Study 301 - Solicited Safety Set \nNo imbalances in any categories between vaccine and placebo recipientsSafety Set\nBased on April 30, 2023 cutoff\nNE-17\nAdverse Events of Special Interest (AESI)\nNeurological Disorders\nNo cases of Guillain- Barre syndrome or acute disseminated \nencephalomyelitis (ADEM) \nNo imbalance observed for other neurological disorders including Bell’s \npalsy/facial paralysis\nCardiac Events\nNo imbalance observed in cardiac arrhythmias such as atrial fibrillation\nNo CEAC adjudicated cases of:\nAcute myocarditis in vaccine recipients\nAcute pericarditis in vaccine recipients with onset < 42 daysStudy 301 \nSafety Set\nCEAC – Cardiac Event Adjudication Committee\n Based on April 30, 2023 cutoff\nNE-18\nEfficacy\nStudy 301\nNE-19\nKey Efficacy Endpoints \nStudy 301\nVaccine efficacy to prevent first episode of RSV -LRTD (Lower Respiratory Tract Disease) \nbetween 14 days and 12 months post -injection\n≥ 2 signs/symptoms\n≥ 3 signs /symptoms\nPrimary Efficacy Objectives\nVaccine efficacy to prevent:\nFirst episode of RSV -ARD (Acute Respiratory Disease) between 14 days and 12 months post -\ninjection\nFirst hospitalization associated with RSV -ARD or RSV -LRTD between 14 days and 12 months \npost-injection\nKey Secondary Efficacy Objectives\nVaccine efficacy against RSV -LRTD with shortness of breath (a surrogate measure of more severe \ndisease)1, 2\nExploratory Endpoint\n1. Falsey et al NEJM , 2005; 2. Panozzo et al ESWI , 2023  \nNE-20\nDefinitions of LRTD and ARD\nStudy 301\n+\nRT-PCR\nConfirmed\n RSVRSV Lower Respiratory Tract Disease (LRTD)\nNew or Worsening of ≥ 2 or ≥ 3 of Signs/Symptoms for ≥ 24 Hours\nRSV Acute Respiratory Disease (ARD) \nNew or Worsening of ≥ 1 Signs/Symptoms for ≥ 24 Hours\nSinus \nPainHoarsenessStuffy \nNoseTachypneaShortness \nof BreathSputum \nProduction\nWheezing\nSore \nThroatRunny \nNoseChills HypoxemiaFeverPleuritic \nChest PainCoughTachypneaShortness \nof BreathSputum \nProduction Wheezing \nand/or \nrales and/or \nrhonchiFever and/ \nor CoughHypoxemiaPleuritic \nChest Pain\nLRTD cases are a subset of the ARD cases \nRSV surveillance was conducted year-round throughout study follow-up\nNE-21\nPrimary Analysis\nStudy 301\nPer Protocol Analysis – November 30, 2022 data cutoff\nNE-22Efficacy of mRNA -1345 Against RSV LRTD and RSV ARD \namong Adults ≥ 60 Years\nStudy 301  - Per Protocol Analysis\nVaccine efficacy for primary and key secondary endpoints (median 3.7 months) met lower bound \nof CI criterion (>20%)\nRegulatory criteria for licensure metPrimary Analysis\n1. Alpha adjusted CI: 95.88% for RSV LRTD ≥ 2 symptoms, 96.36% for RSV LRTD ≥ 3 symptoms, 95.0% for RSV ARD\nWilson et al. NEJM,  2023Cases, n (%)\nRSV Vaccine \n(mRNA- 1345)\n(N = 17,572)Placebo\n(N = 17,516)Vaccine Efficacy (%) \nBased on Hazard Ratios1\nRSV LRTD\n≥ 2 symptoms9 (0.05%) 55 (0.31%)83.7%\n(66.0%, 92.2%)\nRSV LRTD\n≥ 3 symptoms3 (0.02%) 17 (0.10%)82.4% \n(34.8%, 95.3%)\nRSV ARD 26 (0.15%) 82 (0.47%)68.4%\n(50.9%, 79.7%)\nNE-23\nVaccine Efficacy Against RSV -A and RSV-B by Endpoint \nNumbers of Events\nRSV Vaccine \n(mRNA -1345)\n(N = 17,572)Placebo\n(N = 17,516)Vaccine Efficacy\n(CI)\nRSV LRTD\n≥ 2 Symptoms Overall 9 55 83.7% (66.0, 92.2)\nRSV-A 3 36 91.7% (73.0, 97.4)\nRSV-B 6 19 68.5% (21.1, 87.4)\nRSV LRTD≥ 3 Symptoms Overall 3 17 82.4% (34.8, 95.3)\nRSV-A 1 10 90.0% (22.0, 98.7)\nRSV-B 2 7 71.5% (-37.0, 94.1)\nRSV-ARDOverall 26 82 68.4% (50.9, 79.7)\nRSV-A 11 51 78.5% (58.8, 88.8)\nRSV-B 15 31 51.7% (10.6, 73.9)Study 301 -  Per-Protocol Efficacy Set\n-40 -20 0 20 40 60 80 100Primary Analysis\nEfficacy was observed for both RSV -A and RSV -B\nFewer cases of LRTD ≥ 3 symptoms resulted in larger confidence intervals for both subtypesVaccine Efficacy, % (Adjusted CIs)\nWilson et al. NEJM , 2023\nNE-24Vaccine Efficacy by Age, Comorbidities, and Frailty \nAgainst RSV LRTD ≥ 2 Symptoms  \nNumbers of Events\nRSV LRTD with ≥ 2 Symptoms RSV Vaccine \n(mRNA -1345)\n(N = 17,572)Placebo\n(N = 17,516)Vaccine Efficacy\n(CI)\nOverall 9 / 17,572 55 / 17,516 83.7% (66.0, 92.2)\nAge60 – 69 Years 8 / 11,168 33 / 11,118 76.0% (48.0, 88.9)\n70 – 79 Years 1 / 5,440 22 / 5,416 95.4% (65.9, 99.4)\n≥ 80 Years 0 / 964 0 / 982 –\nComorbiditiesNo Comorbidities 7 / 12,377 38 / 12,431 81.6% (58.8, 91.8)\n≥ 1 Comorbidities 2 / 5,195 17 / 5,085 88.4% (49.9, 97.3)\nFrailty StatusFit (0-3) 8 / 13,396 45 / 13,250 82.3% (62.5, 91.7)\nVulnerable/Frail (≥ 4) 0 / 3,781 6 / 3,858 100.0% (NE, 100.0)Study 301 - Per-Protocol Efficacy Set\n-40 -20 0 20 40 60 80 100Primary Analysis\nVaccine Efficacy, % (Adjusted CIs)\nCase splits favorable for mRNA -1345 with respect to age, comorbidities, and frailty\nNo cases observed in ≥ 80- year-olds \nWilson et al. NEJM, 2023; NE - nonestimable\nComorbidities include COPD, CHF, asthma, chronic respiratory disease, diabetes, advanced liver disease, advanced renal disease\nNE-25\nCases, n (%)\nRSV Vaccine \n(mRNA -1345)\n(N = 17,572)Placebo\n(N = 17,516)Vaccine Efficacy (%) \nBased on Hazard Ratios \n(95% CI)\nRSV-LRTD Associated \nShortness of Breath1,2 2 (0.01%) 15 (0.09%)86.7% \n(41.9%, 97.0%)\nMedically Attended RSV -LRTD \n(≥ 2 Symptoms and ER/Urgent Care)0 5 (0.03%) NEEfficacy Against Severe (based on Shortness of Breath) \nand Medically Attended LRTD Among Adults ≥ 60 Years\nStudy 301 - Post Hoc Analysis/Per Protocol Analysis\nPost Hoc Analysis\nShortness of breath is a key driver of seeking a higher level of care1,2 \nVaccine is efficacious in preventing shortness of breath associated with RSV -LRTD\nCase split favorable for medically attended RSV -LRTD (ER/urgent care visits)\nBased on Nov 30, 2022 cutoff; NE - nonestimable\n1.Falsey et al NEJM, 2005; 2. Panozzo et al. ESWI , 2023 \nNE-26\nAdditional Analysis\nStudy 301\nPer Protocol Analysis – April 30, 2023 data cutoff\nNE-27Efficacy of mRNA -1345 Against RSV LRTD and RSV ARD \namong Adults ≥ 60 Years\nStudy 301 - Per Protocol Analysis\nAdditional Analysis \nVaccine protection continues over a longer period (median 8.6 months) through high-transmission 2022/2023 \nRSV season\nLower bound of the confidence interval continued to exceed 20%Cases, n (%)\nRSV Vaccine \n(mRNA- 1345)\n(N = 18,112)Placebo\n(N = 18,045)Vaccine Efficacy (%) \nBased on Hazard Ratios \n(95% CI)\nRSV LRTD\n≥ 2 symptoms47 (0.26%) 127 (0.70%)63.3%\n(48.7%, 73.7%)\nRSV LRTD\n≥ 3 symptoms19 (0.10%) 51 (0.28%)63.0% \n(37.3%, 78.2%)\nRSV ARD 86 (0.47%) 185 (1.03%)53.9%\n(40.5%, 64.3%)\nNE-28Cumulative Incidence Curve – Efficacy Against RSV \nLRTD with ≥ 2 Symptoms among Adults ≥ 60 Years\nStudy 301 - Per-Protocol Efficacy Set\nData cutoff date: Apr 30, 2023; *based on hazard ratio Additional Analysis \nCumulative \nIncidence \nRate\n(%)\nTime from Randomization (Months)Vaccine Efficacy *\n(95% CI)\n63.3%\n(48.7%, 73.7%)\n8.6 months median \nfollow -up (range \n0.5-17.7 months)\nSeparation in curves observed early and  sustained through follow -up \nmRNA -1345 18112 18040 17971 17886 17789 17355 17076 14191 10634 7534 5073 3474 2327\nPlacebo 18045 17940 17845 17735 17623 17185 16908 14060 10591 7460 5021 3442 23030.01.1\n1.0\n0.9\n0.8\n0.7\n0.6\n0.5\n0.4\n0.3\n0.2\n0.1\n0 1 2 3 4 5 6 7 8 9 10 11 12Placebo\nRSV Vaccine \n(mRNA -1345)\nnumber at risk\nNE-29\nVaccine Efficacy Against RSV -A and RSV-B by Endpoint \nNumbers of Events\nRSV Vaccine \n(mRNA -1345)\n(N = 18,112)Placebo\n(N = 18,045)Vaccine Efficacy\n(CI)\nRSV LRTD\n≥ 2 Symptoms Overall 47 127 63.3% (48.7, 73.7)\nRSV-A 24 78 69.4%  (51.7, 80.6)\nRSV-B 22 50 56.3%  (27.9, 73.5)\nRSV LRTD\n≥ 3 Symptoms Overall 19 51 63.0% (37.3, 78.2)\nRSV-A 10 30 66.9%  (32.2, 83.8)\nRSV-B 9 22 59.3%  (11.7, 81.3)\nRSV-ARDOverall 86 185 53.9% (40.5, 64.3)\nRSV-A 43 106 59.7%  (42.5, 71.7)\nRSV-B 42 80 47.9%  (24.3, 64.1)Study 301 - Per-Protocol Efficacy Set\n-40 -20 0 20 40 60 80 100\nVaccine Efficacy, % (Adjusted CIs)Additional Analysis \nEfficacy was observed for both RSV -A and RSV -B\nNE-30Vaccine Efficacy by Age, Comorbidities, and Frailty \nAgainst RSV LRTD ≥ 2 Symptoms  \nStudy 301 - Per-Protocol Efficacy Set\nCase splits favorable for mRNA -1345 with respect to age, comorbidities, and frailty\nToo few cases in ≥ 80- year-olds to assess efficacy Numbers of Events\nRSV LRTD with ≥ 2 Symptoms RSV Vaccine \n(mRNA -1345)\n(N = 18,112)Placebo\n(N = 18,045)Vaccine Efficacy\n(CI)\nOverall 47/18,112 127/18,045 63.3% (48.7, 73.7)\nAge60 – 69 Years 31/11,219 77/11,170 60.1%  (39.5, 73.7)\n70 – 79 Years 10/5,464 45/5,439 78.0%  (56.3, 88.9)\n≥ 80 Years 6/1,429 5/1,436 NE\nComorbiditiesNo Comorbidities 31/12,751 76/12,796 59.5%  (38.5, 73.4)\n≥ 1 Comorbidities 16/5,361 51/5,249 69.3%  (46.1, 82.5)\nFrailty StatusFit (0-3) 37/13,417 104/13,274 65.0%  (49.0, 75.9)\nVulnerable/Frail (≥ 4) 9/3,817 17/3,884 46.5%  (-20.0, 76.2)\n-40 -20 0 20 40 60 80 100\nVaccine Efficacy, % (95% CIs)Additional Analysis \nNE - nonestimable\nComorbidities include COPD, CHF, asthma, chronic respiratory disease, diabetes, advanced liver disease, advanced renal disease\nNE-31Efficacy Against Severe LRTD and Hospitalizations \nAmong Adults ≥ 60 Years\nCases, n (%)\nRSV Vaccine (mRNA -\n1345)\n(N = 18,112)Placebo\n(N = 18,045)Vaccine Efficacy  (%) \nBased on Hazard Ratios\n(95% CI)\nRSV-LRTD Associated Shortness of \nBreath1,211 (0.06%) 43 (0.24%)74.6%\n(50.7%, 86.9%)\nRSV LRTD with ≥ 2 Symptoms and \nER/Urgent Care5 (0.03%) 13 (0.07%)61.8%\n(-7.35, 86.45)\nHospitalizations 0 (0%) 2 (0.01%) NEStudy 301 - Post Hoc Analysis/Per Protocol Analysis\nBased on April 30, 2023 cutoff\nNE -  nonestimable\n1. Falsey  et al NEJM , 2005; 2. Panozzo et al ESWI , 2023  Shortness of breath is a key driver of seeking a higher level of care1,2 \nVaccine is efficacious in preventing:\nShortness of breath associated with RSV -LRTD\nMedically attended RSV -LRTD (ER/urgent care visits)\n2 hospitalizations in placebo recipients (both >70 years with comorbid conditions [asthma]; both recovered)Additional Analysis \nNE-32\nImmunogenicity\nStudy 301\nImmunogenicity Subset\nNE-33\nRSV-A \nAssay\nRSV-B \nAssayNeutralizing Antibody Response by RSV Subtype – \nBaseline and Day 29\nStudy 301 - Microneutralization Antibody (IU/mL)\n1350 1305 14257246\n1001,00010,000100,000\nAll Participants Baseline Day 29 Baseline Day 29\n5.1-fold rise\n(N = 333) (N = 1515)mRNA -1345 \n(50 µg)\nPlacebo\nParticipants had \nbaseline titers consistent with prior exposure to \nRSV\nOne dose of 50 μg of \nmRNA -1345 increased \ntiters by:\n>8-fold for RSV -A\n>5-fold for RSV -B2404 2417 255321475\n1001,00010,000100,000\nAll Participants Baseline Day 29 Baseline Day 29\n8.4-fold rise\nGMT\nIU/mL\n(95% CI)\n(N = 333) (N = 1515)Per Protocol Immunogenicity Set\nGMT\nIU/mL\n(95% CI)\nNE-34\nRSV-B \nAssayRSV-A \nAssayNeutralizing Antibody Response by RSV Subtype and Age – \nBaseline and Day 29 \nStudy 301 – Microneutralization Antibody (IU/mL)\nPer Protocol Immunogenicity Set\nBaseline titers similar across age groups\nDay 29 titers and fold rise are similar across age groups60–69 Years 70–79 Years  ≥ 80 Years  \n230922612\n274720374\n270621812\n1001,00010,000100,000\nBaseline Day 29 Baseline Day 29 Baseline Day 29\nGMT\nIU/mL\n(95% CI)GMT\nIU/mL\n(95% CI)\n9.8-fold rise\n 7.5-fold rise\n 8.1-fold rise\n5.5-fold rise\n 4.8-fold rise\n 5.1-fold risemRNA -1345 (50 µg)\n13537457\n14987093\n14167139\n1001,00010,000100,000\nBaseline Day 29 Baseline Day 29 Baseline Day 29(n = 619) (n = 618) (n = 671) (n = 671) (n = 223) (n = 222)\n(n = 617) (n = 616) (n = 672) (n = 671) (n = 223) (n = 222)Age by Decade\nNE-35\nT-cell Responses Following Receipt of mRNA -1345\nCRID- 001 Study - 15 Adults, 50- 75 Years Old\nCD4+ T cells CD8+ T cells\n•Vaccine elicits persistent CD4+ and CD8+ T -cell responses RSV- F antigen specific, Interferon -γ+ T-cells (intracellular cytokine staining assay)\nNE-36Durability of RSV -A and RSV -B Neutralizing Antibody Response with \nmRNA- 1345 and Revaccination \nStudy 101 – Adults 65- 79 Years \n100100010000100000\n0123 6 121314RSV-A Neutralizing Antibody\n100100010000100000\n0123 6 121314\nRSV-B Neutralizing Antibody\nGMT \n(95% CI)\nStudy Month\nStudy Month•RSV-A and RSV -B neutralizing antibodies detectable at 12 months post- vaccination, 2-3 fold above baseline\n•Revaccination at 12 months results in increase in GMT  \n•Revaccination at 1 and 2 years is being evaluated in Phase 3 studiesGMFR from Day 0 10.1 6.96.8 5.5 2.77.37.0\nStudy Month6.46.85.8 4.5 2.55.24.5\nN = 14 -18 adults\nSimorellis et al, ESWI  2023\nNE-37\nConcomitant Administration of RSV Vaccine \n(mRNA1345) with Quadrivalent Influenza Vaccine (Afluria) or Bivalent COVID -19 Vaccine \n(mRNA-1273.214)\nStudy 302, Parts A & B\nNE-38\nStudy 302: Safety and Immunogenicity Study of Concomitant Administration \nof mRNA- 1345 with Quadrivalent Influenza Vaccine (Afluria) or COVID -19 \nBivalent Vaccine in Adults ≥ 50\nPlanned \nSample Size Randomized\nRSV Vaccine PlaceboCOVID- 19 \nBivalent Vaccine\nRSV VaccineCOVID- 19 \nBivalent VaccinePlacebo\nCOVID- 19 \nBivalent VaccinePlacebo PlaceboPart B\nGroup 1\nGroup 2\nGroup 3RSV Vaccine Placebo\nRSV VaccineQuadrivalent \nFlu Vaccine\nQuadrivalent \nFlu VaccinePlacebo\nGroup 1\nGroup 2\nGroup 3Part ADay 1\nDay 29420 2491\n600 690\n600 692\n560 562\n560 566\n560 563\n1.Due to randomization error, sample size lower than planned\nNE-39\nComparison of Day 29 Geometric Mean Titer Ratio (GMR) – Concomitant vs \nNonconcomitant Administration of mRNA -1345 and Quadrivalent Influenza Vaccine\nAntibody GMR (95% CI)\nRSV-A Neutralizing Antibody (IU/mL) 0.81 (0.67, 0.97)\nRSV-B Neutralizing Antibody (IU/mL) 0.85 (0.73, 1.00)\nInfluenza A/H1N1 Antibody 0.89 (0.77, 1.03)\nInfluenza A/H3N2 Antibody 0.97 (0.86, 1.09)\nInfluenza B/Phuket Antibody 0.91 (0.81, 1.02)\nInfluenza B/Washington Antibody 0.93 (0.82, 1.05)Study 302, Part A\n0.5 1 1.5\nAll GMR non -inferiority criteria met (LB of the 2- sided 95% CI of GMR > 0.667)GMR  (95% CI)0.667\nNE-40\nComparison of Day 29 Geometric Mean Titer Ratio (GMR) – Concomitant vs \nNonconcomitant Administration of mRNA -1345 and COVID -19 Bivalent Vaccine\nAntibody GMR (95% CI)\nRSV-A Neutralizing Antibody (IU/mL) 0.80 (0.70, 0.90)\nRSV-B Neutralizing Antibody (IU/mL) 0.89 (0.79, 1.00)\nCOVID- 19 (Wuhan) (AU/ml) 0.96 (0.87, 1.06)\nCOVID- 19 (Omicron) (AU/ml) 1.01 (0.89, 1.14)Study 302, Part B\n0.5 1 1.5\nGMR  (95% CI)0.667\nAll GMR non -inferiority criteria met (LB of the 2- sided 95% CI of GMR > 0.667)\nNE-41Solicited Local Reactions within 7 Days After mRNA -1345 Alone or \nCo-administered with Quadrivalent influenza Vaccine (Afluria) in Adults ≥ 50\nStudy 302, Part A - Solicited Safety Set\nmRNA -1345 + Afluria,  n= 678; mRNA -1345 + placebo, n= 249; Afluria + placebo;  n= 683\nOne grade 4 event (0.4%) of axillary swelling or tenderness in mRNA -1345 + placebo group\nMostly grade 1, onset day 1-2, median duration of 2 days for RSV + Flu Solicited Safety Set\n48% 47%\n26%\n1% 1% 2% 2% 3%1%12%15%\n9%\n0%10%20%30%40%50%60%70%80%90%100%\nmRNA\n+ flumRNA\n+ pboflu +\npbomRNA\n+ flumRNA\n+ pboflu +\npbomRNA\n+ flumRNA\n+ pboflu +\npbomRNA\n+ flumRNA\n+ pboflu +\npboInjection Site Pain Injection Site \nErythemaInjection Site \nSwellingAxillary Swelling \nor Tenderness\n%Grade 1\nGrade 2\nGrade 3 + 4\nRSV + \nAfluriaAfluria + \nPlaceboRSV + \nPlaceboRSV + \nAfluriaAfluria + \nPlaceboRSV + \nPlaceboRSV + \nAfluriaAfluria + \nPlaceboRSV + \nPlaceboRSV + \nAfluriaAfluria + \nPlaceboRSV + \nPlacebo\nNE-42Solicited Systemic Reactions within 7 Days After mRNA -1345 Alone or \nCo-administered with Quadrivalent Influenza Vaccine in Adults ≥ 50\nStudy 302, Part A - Solicited Safety Set\nMostly grade 1, onset day 1-2, median duration of 2 days for RSV + Flu Solicited Safety Set\n20% 21%14%9% 11%7% 9% 11%7%\n0%20%40%60%80%100%\nmRNA +\nflumRNA +\npboflu + pbo mRNA +\nflumRNA +\npboflu + pbo mRNA +\nflumRNA +\npboflu + pbo3%7%2%23% 25%17%26% 25% 22% 24% 23%\n14%\n0%20%40%60%80%100%\nmRNA +\nflumRNA +\npboflu + pbo mRNA +\nflumRNA +\npboflu + pbo mRNA +\nflumRNA +\npboflu + pbo mRNA +\nflumRNA +\npboflu + pboFever Headache Fatigue Myalgia\n%\nArthralgia Nausea / Vomiting Chills\n%Grade 1\nGrade 2\nGrade 3 + 4\nmRNA -1345 + Afluria,  n= 678; mRNA -1345 + placebo, n= 249; Afluria + placebo;  n= 683\nGrade 4 fever reported in  1 recipient of mRNA 1345+ placeboRSV + \nAfluriaAfluria + \nPlaceboRSV + \nPlaceboRSV + \nAfluriaAfluria + \nPlaceboRSV + \nPlaceboRSV + \nAfluriaAfluria + \nPlaceboRSV + \nPlaceboRSV + \nAfluriaAfluria + \nPlaceboRSV + \nPlacebo\nNE-43Solicited Local Reactions within 7 Days After mRNA -1345 Alone or \nCo-administered with COVID -19 Bivalent Vaccine in Adults ≥ 50\nStudy 302, Part B - Solicited Safety Set\nmRNA -1345 + COVID -19, n= 558; mRNA -1345 + placebo, n= 555; COVID -19 + placebo;  n= 557\nNo grade 4 eventsSolicited Safety Set\n61%\n54% 55%\n3% 3% 3% 3% 3% 3%19%17% 15%\n0%10%20%30%40%50%60%70%80%90%100%\nrsv +\ncovidrsv +\npbocovid +\npborsv +\ncovidrsv +\npbocovid +\npborsv +\ncovidrsv +\npbocovid +\npborsv +\ncovidrsv +\npbocovid +\npboInjection Site Pain Injection Site \nErythemaInjection Site \nSwellingAxillary Swelling \nor Tenderness\n%Grade 1\nGrade 2\nGrade 3\nMostly grade 1, onset day 1-2, median duration of 2 days for RSV + COVID -19\nRSV + \nCOVID-19COVID-19 \n+ PlaceboRSV \n+ \nPlaceboRSV + \nCOVID-19COVID-19 \n+ Placebo RSV \n+ \nPlaceboRSV + \nCOVID-19COVID-19 \n+ PlaceboRSV \n+ \nPlaceboRSV + \nCOVID-19COVID-19 \n+ PlaceboRSV \n+ \nPlacebo\nNE-44Solicited Systemic Reactions within 7 Days After mRNA -1345 Alone or \nCo-administered with COVID -19 Bivalent Vaccine in Adults ≥ 50\nStudy 302, Part B - Solicited Safety Set\nMostly grade 1, onset day 1-2, median duration of 2 days for RSV + COVID -19 Solicited Safety Set\n35%\n22%26%\n10%7% 9%22%\n13%17%\n0%20%40%60%80%100%\nmRNA +\nflumRNA +\npboflu + pbo mRNA +\nflumRNA +\npboflu + pbo mRNA +\nflumRNA +\npboflu + pbo8%2% 3%32%27% 30%41%\n30% 33%40%\n27%31%\n0%20%40%60%80%100%\nmRNA +\nflumRNA +\npboflu + pbo mRNA +\nflumRNA +\npboflu + pbo mRNA +\nflumRNA +\npboflu + pbo mRNA +\nflumRNA +\npboflu + pboFever Headache Fatigue Myalgia\n%\nArthralgia Nausea / Vomiting Chills\n%Grade 1\nGrade 2\nGrade 3 + 4\nmRNA -1345 + COVID -19 vaccine,  n= 558; mRNA -1345 + placebo, n= 555; COVID -19 vaccine + placebo;  n= 557\nGrade 4 fever reported in 1 recipient of COVID -19 + placeboRSV + \nCOVID-19COVID-19 \n+ PlaceboRSV \n+ \nPlaceboRSV + \nCOVID-19COVID-19 \n+ PlaceboRSV \n+ \nPlaceboRSV + \nCOVID-19COVID-19 \n+ PlaceboRSV \n+ \nPlaceboRSV + \nCOVID-19COVID-19 \n+ PlaceboRSV \n+ \nPlacebo\nNE-45Safety Events of Interest – Study of Concomitant Administration of \nmRNA- 1345 with Influenza or COVID -19 Vaccine\nNo reports of: \nDeaths, SAEs, or AESIs as assessed as related by the investigator\nAnaphylaxis\nGuillain Barre Syndrome\nAcute disseminated encephalomyelitis (ADEM)\nBell’s palsy/facial paralysis\nAcute myocarditis or acute pericarditisStudy 302 A and B – Based on 6 Months Follow-up\nSafety Set\nNE-46\nSUMMARY\nNE-47\nVaccine efficacious; met all regulatory criteria for licensure\nContinued to be efficacious through median 8.6 months follow -up\nShown to prevent severe RSV disease (based on analysis of shortness of breath\n and medically attended RSV -LRTD)Investigational RSV Vaccine (mRNA -1345)\nSafety\nEfficacy  Vaccine generally well tolerated in >19,500 individuals\nNo GBS, no ADEM, or other safety concerns\nStrong humoral and cellular immune responses\nDetectable through 12 months post -vaccination; boosting observed with 1- year\n revaccination\nRSV-A & RSV -B nAb responses similar across age groups, including\n those ≥ 80 years old\nImmunogenicity\nConcomitant \nAdministration Pre-specified immunogenicity criteria met & and no new safety signals observed \nwith concomitant administration of mRNA -1345 with influenza vaccine or mRNA -\nCOVID -19 vaccineSummary\nNE-48\nTHANK YOU! Investigators\nStudy site personnel\nLaboratory personnel\nMost importantly, the individuals who \nparticipated in these trials", "summary": "© 2024 Moderna, inc. All rights reserved.Overview of Moderna’s  Investigational RSV Vaccine (mRNA-1345) in Adults ≥ 60 Years of Age Advisory Committee on Immunization Practices (ACIP) Rituparna Das, MD, PhD Feb 29, 2024The safety and efficacy of this investigational RSV vaccine have  not been established in any country for any use    Outline of  PresentationOverview of mRNA- 1345, Moderna’s  investigational RSV vaccine Pivotal Phase 2/3 trial Efficacy Safety Immunogenicity Persistence of…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-28-29-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-02-28-29/02-RSV-Adults-Das-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 48}
{"title": "03 RSV Adults Woodruff 508", "content": "Centers for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nChronic Conditions as Risk Factors for RSV -Associated \nHospitalization\nRebecca C. Woodruff, PhD, MPH\nEpidemiologist, Centers for Disease Control and Prevention\nFebruary 29, 2024Advisory Committee on Immunization Practices Meeting\n \nInformation is needed about which chronic conditions \nincrease the risk of hospitalization for RSV infection.\n2\nResearch Questions\nWhich chronic medical conditions are associated with higher rates of \nRSV-associated hospitalization among community -dwelling adults \naged ≥50 years?\nWhat are the rate ratios comparing RSV hospitalization rates among \ncommunity -dwelling adults aged ≥50 years  with and without \nchronic medical conditions?\nHow do the rates and rate ratios comparing RSV hospitalization rates \namong community -dwelling adults aged ≥50 years with and without \nchronic medical conditions vary by age group ?\n3\nMethods\nWe leveraged multiple data sources to calculate RSV -\nassociated hospitalization rates during the 2017 -2018 RSV \nseason by chronic condition and age group.\nNumerator\n Denominator\n•RSV-Associated Hospitalization \nSurveillance Network (RSV -NET)•Behavioral Risk Factor Surveillance \nSystem (BRFSS)\n•Census population counts\nMethods adapted from Ko JY , Danielson ML, Town M, Derado  G, Greenlund  KJ, Daily Kirley  P , Alden NB, Yousey -Hindes  K, Anderson EJ, Ryan PA, Kim S, Lynfield  R, Torres SM, Barney GR, Bennett NM, Sutton M, Talbot HK, Hill M, Hall AJ, Fry AM, Garg S, Kim L. Risk Factors for Coronaviru s \nDisease 2019 (COVID -19)-Associated Hospitalization: COVID -19-Associated Hospitalization Surveillance Network and Behavioral Risk  Factor Surveillance System. Clin Infect Dis. 2021 Jun 1; 72(11):e695 -e703. https://doi.org/10.1093/cid/ciaa1419  5\n▪RESP -NET: a population -based hospitalization \nsurveillance platform\n▪Active, population -based surveillance of \nlaboratory -confirmed RSV -associated \nhospitalizations\n–>300 acute -care hospitals, 58 counties in 12 states\n–~8.6% of U.S. population\n▪Tests positive for RSV within 14 days prior to \nor during hospitalization\n–Clinician -driven testingRSV -Associated Hospitalization Surveillance Network \n(RSV -NET)\nCalifornia\nOregon\nUtah\nColorado\nNew\nMexicoMichigan\nMarylandNew York\nConnecticut\nTennessee\nGeorgia\nRSV-NET surveillance areas \nwith percentage of state \npopulation represented by \nparticipating RSV -NET \ncounties\nMinnesota\n6\nBehavioral Risk Factor Surveillance System \n(BRFSS) Overview\n•Annual telephone -based survey in the US, DC, and \nselect territories \n•Self-reported history of select chronic conditions\n•Representative of the state population\n•Eligible participants:\n•Civilian, community -dwelling residents \n•Aged  ≥18 years\n7\n▪Asthma\n▪Chronic kidney disease (CKD)\n▪Chronic obstructive pulmonary disease (COPD)\n▪Coronary artery disease (CAD)\n▪Current smoking\n▪Diabetes mellitus\n▪Obesity (body mass index 30 -39 kg/m2)\n▪Severe obesity (body mass index ≥40 kg/m2)\n▪StrokeWe evaluated 9 chronic medical conditions as potential risk \nfactors for RSV -associated hospitalization.\n8\nWe calculated RSV -associated hospitalization rates using \nthe following methods.\nObtained counts of RSV -associated hospitalizations among community -dwelling \nadults aged ≥50 years with and without chronic medical conditions during the 2017 -\n2018 surveillance season (RSV -NET)\nObtained estimated counts of community -dwelling adults aged ≥50 years with and \nwithout chronic medical conditions in 2018 for the 38 -county RSV -NET catchment \narea\nCalculated RSV-associated hospitalization rates (per 100,000 population) among \nadults with and without chronic medical conditions stratified by age group (50 -64, \n65-74, ≥75 years)\nApplied burden multipliers to the rates to account for frequency of RSV testing \namong adults hospitalized with respiratory illness and sensitivity of diagnostic tests\n9\nWe calculated RSV -associated hospitalization rate ratios \nusing the following methods.\nDivided the RSV -associated hospitalization rates in adults with vs. without \nchronic medical conditions (ages 50 -64, 65 -74, ≥75 years)\nUsed Monte Carlo simulation and generalized Poisson models to estimate rate \nratios adjusted for sex and race or ethnicity group and 95% Monte Carlo \n(confidence) intervals\n10\nPreliminary Results\nAdults Aged 50 -64 Years\n0100200300400500\n≥40 30-39 <30\nAll Chronic\nKidney\nDiseaseCOPD Body Mass Index\n(kg/m2)Coronary\nArtery\nDiseaseAsthma Diabetes Current\nsmokerStrokeRSV-associated hospitalization rate \n(per 100,000)RSV-associated hospitalization rates among community -dwelling adults aged 50-64 years with and without \nchronic medical conditions, 2017 -2018 surveillance season\nCOPD: Chronic Obstructive Pulmonary Disease. Data are preliminary and unpublished. Rates of laboratory -confirmed RSV -associated hospitalization account for under -detection of RSV infection among hospitalized adults and sensitivity of diagnostic tests; \nrates exclude residents of nursing homes and long -term care facilities and are not adjusted for sex or race/ethnicity group. Adj usted rate ratios are derived from generalized Poisson models using Monte Carlo simulation methods and adjust for sex and rac e \nand ethnicity group. 7.9\n(4.7–13.8)\n5.8\n(3.7–9.3)\n3.3\n(2.1–5.1)3.7\n(2.4–5.7) 2.8\n(1.9–4.1)2.4\n(1.4–4.0)4.2\n(2.5–7.1)\n1.5\n(1.0–2.3)1.4\n(0.7–2.8)Adjusted rate ratio:\n12\nAdults Aged 50 -64 Years\n0100200300400500\n≥40 30-39 <30\nAll Chronic\nKidney\nDiseaseCOPD Body Mass Index\n(kg/m2)Coronary\nArtery\nDiseaseAsthma Diabetes Current\nsmokerStrokeRSV-associated hospitalization rate \n(per 100,000)RSV-associated hospitalization rates among community -dwelling adults aged 50-64 years with and without \nchronic medical conditions, 2017 -2018 surveillance season\nCOPD: Chronic Obstructive Pulmonary Disease. Data are preliminary and unpublished. Rates of laboratory -confirmed RSV -associated hospitalization account for under -detection of RSV infection among hospitalized adults and sensitivity of diagnostic tests; \nrates exclude residents of nursing homes and long -term care facilities and are not adjusted for sex or race/ethnicity group. All adults \n≥75 years\n13\nAdults Aged 65 -74 Years\n0100200300400500600700800\n≥40 30-39 <30\nAll Chronic\nKidney\nDiseaseBody Mass Index\n(kg/m2)COPD Asthma Current\nsmokerCoronary\nArtery\nDiseaseDiabetes StrokeRSV-associated hospitalization rate \n(per 100,000)RSV-associated hospitalization rates among community -dwelling adults aged 6 5-74 years with and without \nchronic medical conditions, 2017 -2018 surveillance season\n6.1\n(3.7–10.7)\n4.2\n(2.7–6.7)3.3\n(2.0–5.9)2.5\n(1.6–4.2)2.2\n(1.5–3.3)4.5\n(2.3–8.8)\n1.5\n(1.0–2.4)2.3\n(1.4–3.8) 1.6\n(0.8–3.0)Adjusted rate ratio:\nCOPD: Chronic Obstructive Pulmonary Disease. Data are preliminary and unpublished. Rates of laboratory -confirmed RSV -associated hospitalization account for under -detection of RSV infection among hospitalized adults and sensitivity of diagnostic tests; \nrates exclude residents of nursing homes and long -term care facilities and are not adjusted for sex or race/ethnicity group. Adj usted rate ratios are derived from generalized Poisson models using Monte Carlo simulation methods and adjust for sex and rac e \nand ethnicity group. \n14\nAdults Aged 65 -74 Years\n0100200300400500600700800\n≥40 30-39 <30\nAll Chronic\nKidney\nDiseaseBody Mass Index\n(kg/m2)COPD Asthma Current\nsmokerCoronary\nArtery\nDiseaseDiabetes StrokeRSV-associated hospitalization rate \n(per 100,000)RSV-associated hospitalization rates among community -dwelling adults aged 6 5-74 years with and without \nchronic medical conditions, 2017 -2018 surveillance season\nCOPD: Chronic Obstructive Pulmonary Disease. Data are preliminary and unpublished. Rates of laboratory -confirmed RSV -associated hospitalization account for under -detection of RSV infection among hospitalized adults and sensitivity of diagnostic tests; \nrates exclude residents of nursing homes and long -term care facilities and are not adjusted for sex or race/ethnicity group. All adults \n≥75 years\n15\nAdults Aged ≥75 Years\n0200400600800100012001400160018002000\n≥40 30-39 <30\nAll Chronic\nKidney\nDiseaseBody Mass Index\n(kg/m2)COPD Asthma Coronary\nArtery\nDiseaseDiabetes Stroke Current\nsmokerRSV-associated hospitalization rate \n(per 100,000)0.9\n(0.4–2.2)1.9\n(1.2–2.9)RSV-associated hospitalization rates among community -dwelling adults aged ≥75 years with and without \nchronic medical conditions, 2017 -2018 surveillance season\n6.1\n(3.6–12.6)\n4.2\n(2.7–6.6) 2.9\n(1.5–6.2)2.9\n(1.3–6.7)\n1.1\n(0.7–1.7)1.6\n(1.0–2.6)1.5\n(0.8–3.1)Adjusted rate ratio:\nCOPD: Chronic Obstructive Pulmonary Disease. Data are preliminary and unpublished. Rates of laboratory -confirmed RSV -associated hospitalization account for under -detection of RSV infection among hospitalized adults and sensitivity of diagnostic tests; \nrates exclude residents of nursing homes and long -term care facilities and are not adjusted for sex or race/ethnicity group. Adj usted rate ratios are derived from generalized Poisson models using Monte Carlo simulation methods and adjust for sex and rac e \nand ethnicity group. \n16\nRSV -Associated Hospitalization Rates by Chronic Condition \nand Age Group\n02004006008001000120014001600\n50-64\n65-74\n≥75\n50-64\n65-74\n≥75\n50-64\n65-74\n≥75\n50-64\n65-74\n≥75\n50-64\n65-74\n≥75\n50-64\n65-74\n≥75\n50-64\n65-74\n≥75\n50-64\n65-74\n≥75\n50-64\n65-74\n≥75\n50-64\n65-74\n≥75\nAll adults Chronic\nKidney\nDiseaseCOPD Severe \nobesity\n(BMI ≥40)Asthma Coronary\nArtery\nDiseaseDiabetes\nmellitusStroke Obesity\n(BMI 30-\n39)Current\nsmokerRSV-associated hospitalization rate \n(per 100,000)RSV-associated hospitalization rates among community -dwelling adults aged ≥50 years with chronic medical \nconditions, 2017 -2018 season\nCOPD: Chronic Obstructive Pulmonary Disease. Data are preliminary and unpublished. Rates of laboratory -confirmed RSV -associated hospitalization account for under -detection of RSV infection among hospitalized adults and sensitivity of diagnostic tests; \nrates exclude residents of nursing homes and long -term care facilities and are not adjusted for sex or race/ethnicity group.\n17\nAdjusted Rate Ratios for RSV -Associated Hospitalization \nby Chronic Condition among Adults Aged ≥50 Years\n6.5\n4.6\n3.12.8\n2.42.0 1.91.51.1\n0.11.010.0100.0\nChronic\nKidney\nDiseaseCOPD Asthma Severe\nobesityCoronary\nArtery\nDiseaseDiabetes\nmellitusCurrent\nsmokerStroke ObesityaRR\nCOPD: Chronic Obstructive Pulmonary Disease. Data are preliminary and unpublished. Adjusted rate ratios are derived from gene ralized Poisson models using Monte Carlo simulation methods and adjust for sex and race and ethnicity group. 18\nRSV -Associated Hospitalization Rates by \nCombinations of Chronic Conditions\nBy Number of Chronic Conditions\n02004006008001000\n50-64\nyears65-74\nyears≥75 \nyearsRSV-associated hospitalization rate \n(per 100,000)RSV-associated hospitalization rates* among community -dwelling adults aged ≥50 years by \nnumber of chronic conditions and age group, 2017 -2018 season\n10.6\n(6.3–18.6)6.4\n(3.7–11.2)\n2.9\n(1.7–5.1)2.6\n(1.4–4.9)2.6\n(1.4–4.7)12.4\n(7.8–20.2)Adjusted rate ratio:\n* Data are preliminary and unpublished. Rates of laboratory -confirmed RSV -associated hospitalization account for under -detection o f RSV infection among hospitalized adults and sensitivity of diagnostic tests; rates exclude residents of nursing homes and \nlong -term care facilities and are not adjusted for sex or race/ethnicity group. Adjusted rate ratios are derived from generalize d Poisson models using Monte Carlo simulation methods and adjust for sex and race and ethnicity group. \n20\nBy Chronic Kidney Disease & Coronary Artery Disease\n0200400600800100012001400160018002000\n50-64\nyears65-74\nyears≥75 \nyearsRSV-associated hospitalization rate \n(per 100,000)RSV-associated hospitalization rates* among community -dwelling adults aged ≥50 years by \nchronic kidney disease (CKD), coronary artery disease (CAD), and age group, 2017 -2018 season\n15.7\n(6.8–37.7)\n7.3\n(3.8–13.9)\n3.1\n(1.6–5.5)10.5\n(4.8–23.3)\n5.7\n(3.0–11.2)\n2.1\n(1.1–4.0)7.9\n(3.5–17.6)\n6.3\n(3.4–13.4)\n1.7\n(0.9–3.2)Adjusted rate ratio:\n* Data are preliminary and unpublished. Rates of laboratory -confirmed RSV -associated hospitalization account for under -detection o f RSV infection among hospitalized adults and sensitivity of diagnostic tests; rates exclude residents of nursing homes and \nlong -term care facilities and are not adjusted for sex or race/ethnicity group. Adjusted rate ratios are derived from generalize d Poisson models using Monte Carlo simulation methods and adjust for sex and race and ethnicity group. \n21\nBy Chronic Kidney Disease & Diabetes\n0200400600800100012001400160018002000\n50-64\nyears65-74\nyears≥75 \nyearsRSV-associated hospitalization rate \n(per 100,000)RSV-associated hospitalization rates* among community -dwelling adults aged ≥50 years by \nchronic kidney disease (CKD), diabetes, and age group, 2017 -2018 season\n12.8\n(6.1–27.7)\n7.3\n(3.4–16.4)\n2.3\n(1.3–3.8)9.0\n(4.6–18.7)\n6.0\n(2.6–13.7)\n1.7\n(1.0–3.0)5.8\n(2.7–13.1)\n7.4\n(4.0–14.9)\n1.4\n(0.8–2.7)Adjusted rate ratio:\n* Data are preliminary and unpublished. Rates of laboratory -confirmed RSV -associated hospitalization account for under -detection of RSV infection among hospitalized adults and sensitivity of diagnostic tests; rates exclude residents of n ursing homes and \nlong -term care facilities and are not adjusted for sex or race/ethnicity group. Adjusted rate ratios are derived from generalize d Poisson models using Monte Carlo simulation methods and adjust for sex and race and ethnicity group. \n22\n▪Denominator data were created based on self -reported history of chronic conditions \nfrom BRFSS\n–~49.9% response rate in 2018\n–Subject to recall & social desirability biases\n▪BRFSS might underestimate true prevalence of select chronic medical conditions, which \nwould drive the rates and rate ratios upwards\n▪Could not assess all chronic medical conditions or potential risk factors of interest \n–Heart failure\n–End-stage renal disease \n–Immunocompromise\n▪Results do not necessarily generalize to non -community -dwelling adults (e.g., residents \nof nursing homes, long -term care facilities, shelters, treatment facilities, or correctional \ninstitutions)Limitations\n23\nSelect chronic medical \nconditions were associated \nwith higher rates of RSV -\nassociated hospitalization \namong community -dwelling \nadults, which varied by \ncondition and age group.\n24\nAcknowledgements\nCenters for Disease Control and Prevention\nCoronavirus and Other Respiratory Viruses Division\n•Gordana Derado, PhD\n•Sarah Hamid, PhD\n•Fiona P . Havers, MD\n•Michael Melgar, MD\n•Huong Pham, MPH\n•Christopher A. Taylor, PhD\nDivision for Heart Disease and Stroke Prevention\n•Fleetwood V. Loustalot, PhD\n•Elizabeth Lundeen, PhD\n•Ahlia Sekkarie, PhD\nRSV-Associated Hospitalization Surveillance Network (RSV -NET) Site \nInvestigators, Surveillance Officers, and Staff 25\nFor more information, contact CDC\n1-800 -CDC -INFO (232 -4636)\nTTY:  1 -888 -232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention.\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.", "summary": "Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. Chronic Conditions as Risk Factors for RSV -Associated  Hospitalization Rebecca C. Woodruff, PhD, MPH Epidemiologist, Centers for Disease Control and Prevention February…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-28-29-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-02-28-29/03-RSV-Adults-Woodruff-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 26}
{"title": "04 RSV Adults Black 508", "content": "Centers for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nRSV Vaccination Implementation Update\nCarla Black, PhD\nSurveillance and Epidemiology Branch\nImmunization Services Division, NCIRD, CDC\nAdvisory Committee on Immunization Practices \nFebruary 29, 2024\nData reported by jurisdiction Immunization Information Systems\nVaccination coverage estimates by demographic characteristics and high risk  \nconditions, National Immunization Survey\nDoses administered in pharmacies and physician offices, by product type, IQVIA\nVaccination attitudes and concerns, CDC Omnibus Surveys\nRSV vaccine implementation considerationsPresentation Outline\n2\nData Reported by Jurisdiction Immunization \nInformation Systems (IIS)\nPercent of Adults 60 Years and Older Who Have Received ≥1 Dose RSV Vaccine \nReported by Jurisdiction Immunization Information Systems, Through December 2023\n•Among the currently reporting 37 state and city IIS jurisdictions, RSV vaccination coverage among adults 60 years and older ranged from 4.6% to 17.9%\n4\nNational Immunization Survey (NIS) Data \nUpdate\nNational Immunization Survey -Adult COVID Module (NIS -ACM) Methods\n•The NIS- ACM is a random- digit -dial cellular telephone survey of adults age ≥18 years in the U.S.\n•Respondents are sampled within all 50 states, District of Columbia, five local jurisdictions (Bexar County TX, \nChicago IL, Houston TX, New York City NY , and Philadelphia County PA), Puerto Rico and the U.S. Virgin Islands (sampled in 2023 only).\n•Data are weighted to represent the non- institutionalized U.S. population.\noEstimates from the NIS -ACM may differ from estimates based on other data sources, and are subject to errors resulting \nfrom incomplete sample frame (exclusion of households without cell phones), selection bias (survey respondents may \nbe more likely to be vaccinated than non -respondents), and errors in self -reported vaccination status. Estimates are \nweighted to selected sociodemographic characteristics of the U.S. population to reduce possible bias from incomplete \nsample frame and selection bias.\n•All responses are self- reported.\n•Enhanced weekly estimates: \noCoverage estimates are based on all interviews through the current week and represent approximately the cumulative \npercent vaccinated by mid -week. Each week, estimates for prior weeks are recalculated using the additional interviews \nconducted that week (combined with all previous interviews).\noEstimates for vaccination intent are based on interviews conducted that week and are adjusted to the cumulative vaccination coverage estimate for that week.\n•Kaplan -Meier estimates:\noBased on interviews conducted September 24, 2023 –January 27, 2024\noKaplan -Meier estimation procedure used to estimate RSV vaccination coverage through end of December 2023\n•Additional information available at: About the National Immunization Surveys6\n4.8 5.2 6.5 8.2 9.1 11.4 12.6 13.5 13.9 15.9 16.7 17.0 17.3 17.4 20.2 20.6 20.9 21.4 22.420.9 21.8 20.0 19.6 17.516.917.8 16.6 14.415.6 14.2 12.214.8 16.815.8 14.4 15.4 11.713.350.4 50.345.547.842.742.843.5 45.042.640.4 38.8 39.238.041.6 37.5 38.8 35.1 39.438.324.0 22.728.124.430.7 28.8 26.1 24.829.1 28.1 30.3 31.6 29.824.2 26.5 26.1 28.6 27.5 26.1\n0255075100Weighted %• Among adults aged ≥60 years responding to the National Immunization Survey through February  3, 22.4%  (95% CI: 21.1- 23.6)  reported having received an RSV vaccine.\n• 13.3% (95% CI: 11.5- 15.1) of adults  ≥60 years  said they definitely will get vaccinated, and 26.1% (95% CI: 23.7 -28.4) said they probably or definitely will not get \nvaccinated.\nProbably or definitely will not get RSV vaccine\nProbably will get RSV vaccine or unsureDefinitely will get RSV vaccineReceived RSV vaccineRSV Vaccination Status and Intent Among Adults 60 Years and Older\nNational Immunization Survey-Adult COVID Module (NIS -ACM)\nWeekly RSV Vaccination Status and Intent Among \nAdults Age ≥60 Years, NIS -ACM (n = 97,574)\n7\n12.4*22.53.2*14.0*12.9*16.714.5*24.4*29.1*24.9*19.4*24.0*11.11.7*19.720.414.220.0\n0 20 40 60 80 100Multi/Other, non-HispanicWhite, non-Hispanic (Ref)NH/OPI, non-HispanicHispanicBlack, non-HispanicAsian, non-HispanicAI/AN, non-Hispanic80+75-7970-7465-6965+60-64 (Ref)50-59**MaleFemale (Ref)Overall 50+**Overall 60+\nWeighted % (95% CI)RSV vaccination coverage  among adults 60 years and older, by end of December 2023\nNational Immunization Survey-Adult COVID Module  (NIS -ACM)\n(N = 91,680)\nAI/AN: American Indian or Alaska Native; NH/OPI: Native Hawaiian or Other Pacific \nIslander; CI: 95% confidence interval; Ref: Referent category .\n*Statistically significant at p<0.05 compared to the referent category.**This bar only among age 50+, all other bars age 60+ only.•20.0% (95% CI: 19.1- 20.9) of adults ≥60 \nyears reported having received an RSV \nvaccine by the end of December 2023.\n•Vaccination was highest among older \nadults and white non- Hispanic adults.\n8\n2.6*11.7*38.52.5*30.517.918.3*20.4*23.2\n0 20 40 60 80 100No COVID vaccinations1+ (not updated)Updated COVID vaccine (Ref)Did notReceived flu vaccine (Ref)Smoker (current/former)SVI: HighSVI: ModerateSVI: Low (Ref)\nWeighted % (95% CI)17.88.1*32.722.228.423.5*23.0*29.3*24.527.7*25.1*\n0 20 40 60 80 100None of the above (Ref)NeurologicalLiver diseaseImmunocompromisedHIV infectionHeart conditionsDiabetesChronic lung diseasesChronic kidney diseaseCancer1+ chronic conditions\nWeighted % (95% CI)RSV vaccination coverage  among adults 60 years and older, by end of December 2023\nNational Immunization Survey -Adult COVID Module  (NIS -ACM)\nImmunocompromised includes immunocompromised state, solid organ or blood stem cell \ntransplant, sickle cell disease or thalassemia; Neurological includes stroke or cerebrovascular hemorrhage, dementia or other neurological, Down syndrome.SVI: Social Vulnerability Index; CI: 95% confidence interval; Ref: Referent category .\n*Statistically significant at p<0.05 compared to the referent category.•Adults ≥60 years with 1+ chronic conditions had significantly higher RSV vaccination coverage (25.1%) than those with no chronic conditions (17.8%).\n•RSV vaccination coverage was higher among those who have received a flu vaccine or who have received the updated 2023- 24 COVID -19 \nvaccine.\n9\n30.0*23.9*20.0*14.318.4*24.0*18.6*14.04.1*20.614.720.9*21.0*28.220.423.820.017.9*21.718.2*20.914.9*24.1\n0 20 40 60 80 100Advanced degreeCollege graduateSome collegeHigh school or less (Ref)Income unknownAbove poverty, >=$75KAbove poverty, <$75KBelow poverty (Ref)UninsuredInsured (Ref)Rural (Ref)SuburbanUrbanHHS Region 10HHS Region 9HHS Region 8HHS Region 7HHS Region 6HHS Region 5HHS Region 4HHS Region 3HHS Region 2HHS Region 1 (Ref)\nWeighted % (95% CI)RSV vaccination coverage  among adults 60 years and older, by end of December 2023\nNational Immunization Survey-Adult COVID Module  (NIS -ACM)\n(N = 91,680)\n•RSV vaccination coverage was highest \nin HHS regions 10 (28.2%; AK,ID,OR,WA ) and \n1 (24.1; CT,ME,MA,NH,RI,VT ).\n•Adults in rural areas had lower vaccination coverage (14.7%).\n•Adults with health insurance had significantly higher vaccination \ncoverage (20.6%) than adults without \ninsurance (4.1%).\n•RSV vaccination increased with increasing household income and \neducation.\nHHS Regions\n1: CT,ME,MA,NH,RI,VT  6: AR,LA,NM,OK,TX\n2: NJ,NY,PR,VI   7: IA,KS,MO,NE\n3: DE,DC,MD,PA,VA,WV  8: CO,MT,ND,SD,UT,WY\n4: AL,FL,GA,KY,MS,NC,SC,TN  9: AZ,CA,HI,NV,GU\n5: IL,IN,MI,MN,OH,WI  10: AK,ID,OR,WAAI/AN: American Indian or Alaska Native; NH/OPI: Native Hawaiian or Other Pacific Islander; CI: 95% confidence interval; Ref: Referent category .\n*Statistically significant at p<0.05 compared to the referent category. 10\n19.8 8.5 14.7 57.1\n0.0 20.0 40.0 60.0 80.0 100.060+ years\nWeighted %RSV vaccine received with flu vaccine RSV vaccine received with COVID vaccine RSV vaccine received with flu + COVID vaccines None of the aboveCoadministration among adults 60 years and older who received an RSV vaccine, January 2024\nNational Immunization Survey -Adult COVID Module (NIS -ACM)\n•Among adults ≥60 years who received an RSV vaccine, \n•19.8% received RSV + Flu vaccines at the same visit\n•8.5% received RSV + COVID vaccines at the same visit\n•14.7% received RSV + Flu + COVID vaccines at the same visit\n11\n84.288.883.9 84.387.7 85.8 84.788.584.6 83.3 82.0 84.411.07.713.4 14.812.111.6 12.510.415.2 15.4 17.6 13.64.8 3.4 2.7 0.9 0.2 2.6 2.9 1.0 0.2 1.3 0.4 2.0\n0%20%40%60%80%100%Weighted %Other non-medical\nMedical\nPharmacy\nMedical: includes doctor's office, health department, clinic or health center, hospital, mass vaccination site, or \"other\" me dically -related place .\nOther non -medical: includes workplace, high school/college/university, or \"other\" nonmedically -related place.Place of RSV Vaccination Among Vaccinated Adults Age ≥60 Years, NIS -\nACM, November 2023 -February 2024Place of RSV vaccination among vaccinated adults 60 years  and older\nNational Immunization Survey -Adult COVID Module (NIS -ACM)\n12\nIQVIA Data Update\nRSV vaccine doses administered in retail pharmacies, long -term care pharmacies, and \nAmerican Medical Association (AMA) physicians’ medical offices* based on claims \nsubmitted to insurers and cash payments (pharmacies only).\nIQVIA data include raw (actual) number of doses administered at a sample of \npharmacies and medical offices of a sample of AMA physicians.\noIQVIA uses a proprietary projection methodology to estimate the projected number of vaccinations administered \ninallpharmacies and medical offices of all AMA physicians.\nNational medical offices projected estimates are based on 2,866 (48%) of the 5,979 \nAMA physicians that IQVIA monitors who  provide RSV vaccinations. \noRange for states is 0% – 73%\noProjected estimates are updated monthly and do not mature until about two months. This results in an increase or \ndecrease in the initial or subsequent estimates for a given week (up to ~10% based on initial evaluations)IQVIA Methodology\nIQVIA data products used: Custom Longitudinal Prescription Claims ( LRx) for retail pharmacies, Custom Medical Claims (Dx) for physician medical offices, SMART National Prescription \nAudit (NPA)*Physicians are a sample of AMA’s proprietary list of physicians. 14\nNational retail pharmacy projected estimates are based on a sample of 40,469 (97%) \nof the 41,583 pharmacies that IQVIA monitors that provide RSV vaccinations.\noRange for states is 94% – 100%\noHigher confidence in the accuracy of national estimates for pharmacy data compared with physician office \ndata\nData are notavailable for vaccinations administered in:\noOther medical settings ( e.g. public health clinics, hospitals)\noNon -medical, non -pharmacy settings ( e.g. workplace, community settings)IQVIA methodology (cont )\n15\nWeekly Cumulative Projected RSV Vaccinations Administered in Retail Pharmacies and \nPhysician Medical Offices, Adults 60 years and older, August 12, 2023 – February 3,  2024. \nData Source: IQVIA*\n*Data Source: IQVIA Custom Weekly LRx and Custom Weekly Dx . Data are available Respiratory Syncytial Virus (RSV) Adult Vaccinations Administered | CDC\n**IQVIA SMART NPA; Data pulled 2/12/24. This is a subset of vaccinations administered in long -term care settings .\n •As of February 3 , 2024, a combined total of 9.65 million RSV vaccinations were administered in retail pharmacies  (9.36 \nmillion) and physician medical offices (291,599).\n•An additional 164,254 RSV vaccinations were administered in long -term care pharmacies.**\n16\nWeekly and Cumulative Projected RSV Vaccinations Administered in Retail Pharmacies by Product, \nAdults 60 years and older, August 12, 2024 – February 2, 2024. Data Source: IQVIA*\n•Of the total 9,360,148 RSV vaccinations administered, 2,933,112 (31%)  were Abrysvo  (Pfizer) and 6,427,035 \n(69%) were Arexvy  (GSK).\n*IQVIA Custom Weekly LRx; File delivery date 2/8/24 .17\nCumulative Projected RSV Vaccinations Administered in Pharmacies, by Age Group and \nProduct, August 4, 2023 – February 2, 2024. Data Source: IQVIA*\n*Data Source: IQVIA SMART National Prescription Audit (NPA) Weekly Extended Insights. Information about these sources is availab le via IQVIA.\n**An additional 1,543 ABRYSVO and 2,860 AREXVY doses were administered to unspecified ages.•As with all persons 60 years and older, for each age group, about 30% received Abrysvo  (Pfizer) and 70% received Arexvy  (GSK). \n18\nWeekly and Cumulative Projected RSV Vaccinations Administered in Physicians’ Medical \nOffices by Product, Adults 60 years and older, August 12, 2024 - February 3, 2024\n•Of the total 291,598 RSV vaccinations administered, 130,720 (45%) were Abrysvo  (Pfizer) and 160,877 (55%) \nwere Arexvy  (GSK) .\n*IQVIA Custom Weekly Dx ; File delivery date 2/20/24 .\n19\nCumulative Projected RSV Vaccinations Administered in Physicians’ Medical Offices, by Age \nGroup and Product, U.S., August 4, 2023– February 3, 2024. Data Source: IQVIA*\n*IQVIA Custom Weekly Dx ; File delivery date 2/20/24 .•Of the 291,598 doses administered, Arexvy  was administered in 53% of adults 60 -64 years and 56% among 65 \nand older\n20\nCumulative Raw (Actual)* RSV Vaccinations Administered Alone or On the Same Day with \nInfluenza and/or COVID Vaccinations, in Retail Pharmacies and Physicians’ Medical Offices Combined, Adults 60 years and older, August 2023 –  December 2023\n*Raw estimates are based on actual sample of pharmacies and medical offices and thus will be different than projected estimat es \npresented elsewhere. IQVIA was unable to provide projected estimates due to complexity of analysis. Vaccination(s) received Number (%) of persons \nreceiving vaccinations\nRSV only (without flu and/or COVID) 3,635,795 (52.0%)\nRSV and flu 1,557,403 (22.3%)\nRSV and COVID 852,591 (12.2%)\nRSV, flu, and COVID 943,676 (13.5%)\nTotal 6,989,465•Of the  ~7 million doses of RSV administered through end of December, 52% were administered alone \nand 48% with either flu or COVID vaccination or all three vaccine on the same day.\n21\nComparison of NIS and IQVIA Projected Doses Administered by Setting\n•Number of doses reported from the NIS projected by applying the vaccination coverage estimates and reported place of \nvaccination to the 2022 U.S. Census population of persons 60 years and older\n•IQVIA data do not capture all medical settings and settings other than medical and pharm.acy .\n•NIS-based estimate for number of doses administered in pharmacies is 14.9 million compared with 9.4 million doses based on \nIQVIA’s projected estimate. NIS-based estimate for all medical settings is 2.4 million compared with 0.29 million in physicians’  \nmedical offices .\n*Data Source: IQVIA SMART NPA and Custom Weekly Dx . NIS ACM Weekly enhanced coverage estimates by week ending February 3, 2024, and\nreported place of vaccination for persons interviewed during the week ending February 3, 2024. 22\nComparison of NIS and IQVIA Projected Estimates to Determine Possible Range of \nVaccination Coverage and Persons Vaccinated\n*Data Source: IQVIA SMART NPA and Custom Weekly Dx . NIS ACM Weekly enhanced coverage estimates by week ending February 3, 2024, and\nreported place of vaccination for persons interviewed during the week ending February 3, 2024.•The IQVIA projected total for physicians’ medical offices and pharmacies combined is 9.7 million (cover age 12.2%).\n•Based on adjusting IQVIA pharmacy estimates by the proportion of people vaccinated in pharmacies reported from the NIS , 11.1 \nmillion doses were administered in all settings (coverage 14.1%).\n•Based on  applying NIS vaccination coverage estimates to the 2022 U.S. Census population of persons 60 years and older , 17.7 \nmillion doses of RSV vaccine were administered in all settings (coverage 22.4%).\n•Using data from both sources, estimated range of persons vaccinated is approximately 11 –18 million and estimated percent of \npersons vaccinated is 14% –22% .\nCumulative number of RSV vaccine doses administered (left bars) and cumulative RSV vaccination coverage (right bars), among persons 60 years and older, as of week ending February 3, 2024.\n23\nRSV Vaccination Attitudes, Omnibus Surveys,      \nJanuary 2024\nData for this analysis were collected through the IPSOS KnowledgePanel  and NORC \nAmeriSpeak  Omnibus Surveys, which use probability -based panels to survey a \nnationally representative sample of U.S. adults aged 18 years and older.\nCDC fields questions about vaccination status, intent, knowledge, attitudes, beliefs, and \nbehaviors on each survey for 2 waves each month, for a combined sample size of ~4,000 respondents.\nData were weighted to represent the non -institutionalized U.S. population and mitigate \npossible non- response bias. All responses are self -reported.Omnibus Survey Methods\n25\n4.6%\n2.6%\n2.5%\n2.4%\n2.3%\n1.9%\n1.5%\n1.0%\n0 25 50 75 100Side\neffects\nDon't know enough\nabout RSV or vaccine\nHaven't\nhad time\nNot worried\nabout RSV\nToo close to\nCOVID vaccine\nVaccine\nfatigue\nNo HCP\nrecommendation\nOther\nreason\nWeighted % (95% confidence interval)Received/definitely will get\n(N=391)\n84.0% reported \"No concerns or issues\"25.8%\n23.0%\n11.8%\n7.7%\n7.5%\n6.2%\n6.1%\n5.9%\n0 25 50 75 100No HCP\nrecommendation\nDon't know enough\nabout RSV or vaccine\nVaccine is\ntoo new\nUnsure if need\nor eligible\nHaven't\nhad time\nToo close to\nCOVID vaccine\nSide\neffects\nVaccine\nfatigue\nWeighted % (95% confidence interval)Probably will get/unsure\n(N=490)\n34.5% reported \"No concerns or issues\"28.2%\n23.0%\n21.2%\n20.7%\n15.7%\n15.6%\n11.9%\n10.6%\n0 25 50 75 100Do not trust\ngov. or pharma\nDon't know enough\nabout RSV or vaccine\nVaccine is\ntoo new\nNot worried\nabout RSV\nSide\neffects\nNo HCP\nrecommendation\nVaccine is not\neffective\nDo not\nneed it*\nWeighted % (95% confidence interval)Probably/definitely will NOT get\n(N=445)\n26.4% reported \"No concerns or issues\"Top RSV Vaccination Concerns and Issues Among Adults ≥60 Years of Age, by\nStatus/Intent, Omnibus Surveys, January 5 -29, 2024 (N=1,326)\nOther response options included: \"Cost/insurance issues ,\" \"Already had RSV*,\" \"HCP recommended against,\" \"Medical reasons*,\" \"Afraid of needles,\" \"Vaccine not available.\"\n*Option not offered to those who already received the vaccine.26\nImplementation Considerations\nTakes time to integrate into systems, gain wide access, increase awareness \namong healthcare providers, and normalize among the population.\nRSV is recommended based on SCDM.\nSCDM recommendations are difficult to implement.\nCoadministration messaging is complex and may result in missed opportunities for \nvaccination.\nInsurance plans have a year to cover the vaccine and not all plans may cover RSV \nvaccine in its first year.\nVaccines are costly, meaning a costly upfront investment to carry the vaccine.\nRSV vaccine is billed under Medicare Part D.\nResidents of long -term care have additional, specific challenges.Potential factors contributing to relatively low vaccination \ncoverage among people ages 60 years and older\n28\nFrequent speaking engagements with healthcare providers to provide education on \nrecommendations and answer questions\nSocial media and other consumer resources to promote vaccination\nResources to increase clinician knowledge of RSV vaccination recommendations and coadministration recommendations\nRegular communication with CMS to communicate challenges with billing\nRegular collaboration and communication with long -term care partners\nPlanning analysis on shared clinical decision makingWhat is CDC doing to increase coverage or RSV vaccination \nin people ages 60+?\n29\nFor more information, contact CDC\n1-800- CDC- INFO (232- 4636)\nTTY:  1 -888- 232- 6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position o f the Centers for Disease Control and Prevention.\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation use. No rights  are implied or extended for use in printing or \nany use by other CDC CIOs or any external audiences.Thank you!", "summary": "Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases RSV Vaccination Implementation Update Carla Black, PhD Surveillance and Epidemiology Branch…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-28-29-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-02-28-29/04-RSV-Adults-Black-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 30}
{"title": "05 RSV Adults Shimabukuro 508", "content": "Centers for Disease Control and Prevention\nNational Center for Emerging and Zoonotic Infectious Diseases\nPost -licensure safety monitoring of respiratory \nsyncytial virus (RSV) vaccines in adults aged ≥60 years\nTom Shimabukuro, MD, MPH, MBA\nOn behalf of the Immunization Safety Office, CDC\nAdvisory Committee on Immunization Practices (ACIP)\nFebruary 29, 2024\nTopics\n▪Background\n▪CDC vaccine safety monitoring for RSV vaccines in adults aged ≥60 years\n•V-safe\n•Vaccine Adverse Event Reporting System (VAERS) (co -managed with FDA)\n•Vaccine Safety Datalink (VSD)\n▪Summary\n2\nBackground\n▪In May 2023, the U.S. Food and Drug Administration licensed two RSV vaccines \nwith approvals for use in adults aged ≥60 years\n•GSK RSV vaccine (trade name Arexvy )*\n•Pfizer RSV vaccine (trade name Abrysvo )†\n▪In June 2023, the Advisory Committee on Immunization Practices (ACIP) voted to \nrecommend that adults aged ≥60 years may receive a single dose of an RSV \nvaccine using shared clinical decision -making‡\n*Package Insert - AREXVY (fda.gov)\n†Package Insert - ABRYSVO (STN 125769/26) (fda.gov) ; Abrysvo was also authorized on August 21, 2023, for use in pregnant people to prevent lower respiratory tract disease caused by \nRSV in infants from birth through six months of age.\n‡ Melgar et al. Use of Respiratory Syncytial Virus Vaccines in Older Adults: Recommendations of the Advisory Committee on Immun ization Practices - United States, 2023. MMWR Morb  \nMortal Wkly  Rep. 2023;72(29):793 -801. 3\nBackground, cont.\n▪The most common reactions in prelicensure studies among adults aged ≥60 \nyears receiving RSV vaccine were:\n•GSK ( Arexvy )* RSV vaccine: pain at the injection site (61%), fatigue (34%), and \nmyalgia (29%)\n•Pfizer ( Abrysvo )† RSV vaccine: fatigue (16%), headache (13%), and pain at the \ninjection site (11%)\n▪In prelicensure studies‡ of Pfizer ( Abrysvo ) RSV vaccine among 20,255 vaccine \nrecipients aged ≥60 years, 2 cases of Guillain -Barré syndrome (GBS) were \nobserved within 42 days of vaccination\n▪In prelicensure studies‡,¶of GSK ( Arexvy ) RSV vaccine among 18,304 vaccine \nrecipients aged ≥60 years, 1 case of GBS was observed within 42 days \nofvaccination\n*Package Insert - AREXVY (fda.gov)\n†Package Insert - ABRYSVO (STN 125769/26) (fda.gov)\n‡ Melgar et al. Use of Respiratory Syncytial Virus Vaccines in Older Adults: Recommendations of the Advisory Committee on Immun ization Practices - United States, 2023. MMWR Morb  \nMortal Wkly  Rep. 2023;72(29):793 -801\n¶Gerber S. ACIP presentation slides, October 25, 2023 ( 1 - GSK RSV - ACIP Core Presentation_CO  (cdc.gov) )4\nBackground, cont.\n▪Clinical trials generally are too small to assess risk for rare adverse events\n▪Due to the small number of GBS cases and size of the prelicensure studies , it is \nnot known at this time whether these GBS cases or other neuroinflammatory \nevents occurred due to random chance, or whether RSV vaccination might \nincrease the risk of these events\n▪Post -licensure safety monitoring* of the RSV vaccines is currently ongoing in:\n•V-safe\n•Vaccine Adverse Reporting System (VAERS)†\n•Vaccine Safety Datalink (VSD)\n•Non -CDC systems \n* Vaccine Safety Monitoring | Vaccine Safety | CDC\n† Clinical Immunization Safety Assessment (CISA) Project contributing expertise to VAERS report reviews 5\n6V-safe\nNew version of V -safe is now available\n▪System requires both previous and \nnew users to create an account\n▪Includes both email and text \nmessaging functionality\n▪Vaccines currently monitored:\n•RSV vaccines for older adults and \npregnant persons\n•COVID -19 vaccines for persons aged 6 \nmonths and older\n7\nV-safe sends health surveys after vaccination\n▪After vaccinations, surveys are sent daily during the first week, then weekly \nthrough 6 weeks\n▪Daily surveys solicit adverse events and health impacts after vaccination\n•Local reactions (e.g., pain, redness, swelling)\n•Systemic reactions (e.g., fatigue, headache, muscle pain)\n•Health impacts (e.g., unable to perform normal daily activities, missed \nschool or work, or received medical care)\n•Additional questions for persons who reported immunocompromise at \nvaccination\n▪Weekly surveys solicit new symptoms or conditions after vaccination\n▪Participants reporting medically attended health impacts are \nencouraged tocomplete a VAERS report\n8\nCharacteristic Vaccine manufacturer (%)\nGSK ( Arexvy )\nN=6,227Pfizer ( Abrysvo )\nN=3,746Manuf  not known\nN=5,772Total\nN=15,745\nFemale sex assigned at birth 59.5 58.0 61.1 59.7\nMedian age (min, max), years 70 (60, 93) 70 (60, 94) 70 (60, 94) 70 (60, 94)\nEthnicity\nHispanic, Latino, or Spanish 2.7 3.8 3.0 3.1\nRace\nAmerican Indian or Alaska Native 0.2 0.2 0.3 0.3\nAsian 2.9 2.7 2.2 2.6\nBlack or African American 4.4 7.2 4.6 5.2\nNative Hawaiian or Pacific Islander 0.2 0.1 0.1 0.1\nWhite 89.2 85.9 88.7 88.2\nOther 0.7 1.2 1.0 1.0\nUnknown/prefer not to answer 1.0 1.4 1.5 1.3\nMultiracial 1.3 1.2 1.6 1.4\n* For 15,745 V -safe participants who enrolled in the RSV 60+ years old protocol and completed ≥1 daily survey during October 20,  2023 -January 28, 2024Demographic characteristics of adults aged ≥60 years \nwho reported RSV vaccination*\n9\nAdditional characteristics of adults aged ≥60 years who \nreported RSV vaccination*\nCharacteristic Vaccine manufacturer (%)\nGSK ( Arexvy )\nN=6,227Pfizer ( Abrysvo )\nN=3,746Manuf  not known\nN=5,772Total\nN=15,745\nImmunocompromised 6.8 6.6 6.4 6.6\nState of health\nExcellent 22.7 22.6 21.5 22.2\nVery good 46.9 46.0 46.1 46.4\nGood 25.1 25.8 26.5 25.8\nFair 4.9 5.3 5.6 5.3\nPoor 0.3 0.2 0.4 0.3\nVaccine(s) co -administered 24.6 33.8 35.6 30.8\nCOVID -19 16.0 22.8 23.5 20.4\nInfluenza 12.6 17.4 20.0 16.5\nCOVID -19 and influenza 7.3 10.1 11.4 9.5\nCOVID -19, influenza, and other 0.7 1.1 1.2 1.0\nOther 4.9 6.0 5.8 5.5\n* For 15,745 V -safe participants who enrolled in the RSV 60+ years old protocol and completed ≥1 daily survey during October 20,  2023 -January 28, 2024 10\nReactions and health impacts reported for adults aged ≥60 years at \nleast once in days 0 -7 following RSV vaccination, by manufacturer*\n1.80.4 1.3 0.51.70.3\n0102030405060708090100\nAny symptoms Injection site reaction Systemic reaction Unable to complete daily\nactivitiesUnable to work Got medical care\nGSK Pfizer Don't know\n* For 15,745 V -safe participants who enrolled in the RSV 60+ protocol and completed ≥1 daily survey during October 20, 2023 -Janu ary 28, 2024 11\nPromoting V -safe – We need your help\n▪Ensure vaccination partners are aware of V -safe\n•Information sheets\n•Social media posts\n•Communications to vaccine recipients\nMaterials and more information available at:\nhttps://www.cdc.gov/vaccinesafety/ensuringsafety/monitoring/v -safe/index.html\n12\nVAERS is the nation’s early warning system for vaccine safety\n+\nVaccine Adverse Event \nReporting System\nhttp://vaers.hhs.gov\n13\nVaccine Adverse Event Reporting System (VAERS)\nStrengths\n▪National data \n▪Accepts reports from anyone\n▪Rapidly detects safety signals \n▪Can detect rare adverse events\n▪Data available to publicLimitations\n▪Reporting bias \n▪Inconsistent data quality and completeness\n▪Lack of unvaccinated comparison group\n▪Not designed to assess causality\n•VAERS accepts all reports from all reporters without making judgments on causality or judging \nclinical seriousness of the event\n•As a hypothesis generating system, VAERS identifies potential vaccine safety concerns that can \nbe studied in more robust data systems14\nVAERS methods\n▪Signs and symptoms of adverse events are coded using Medical Dictionary for \nRegulatory Activities (MedDRA)* Preferred Terms (PTs)   \n•MedDRA PTs are not mutually exclusive\n•A single report may be assigned more than 1 MedDRA PT\n▪Individual report review of serious† reports and medical records, if available\n▪Brighton Collaboration case definitions applied for the neuroinflammatory \nconditions, Guillain -Barré syndrome and acute disseminated encephalomyelitis‡\n▪Reporting rate calculations use doses of vaccine administered for each type of \nRSV vaccine\n▪Empirical Bayesian datamining used to detect disproportional reporting for the \nentire post marketing period for each product¶\n* Welcome to MedDRA | MedDRA\n† Based on the Code of Federal Regulations if one of the following is reported: death, life -threatening illness, hospitalization o r prolongation of hospitalization, permanent disability, congenital anomaly or birth defect\n‡ Sejvar et al. Brighton Collaboration GBS Working Group. Guillain -Barré syndrome and Fisher syndrome: case definitions and guidel ines for collection, analysis, and presentation of immunization safety data. Vaccine. \n2011;29(3):599 -612. Sejvar et al. Encephalitis, myelitis, and acute disseminated encephalomyelitis (ADEM): case definitions and guidelines for coll ection, analysis, and presentation of immunization safety data. \nVaccine. 2007 Aug 1;25(31):5771 -92.\n¶ DuMouchel  W. Bayesian data mining in large frequency tables, with an application to the FDA spontaneous reporting system. Am Statistici an 1999;53:177 –90.15\nSurveillance of Adverse Events of Special Interest (AESI) \nafter RSV vaccination\n▪Primary AESIs\n•Selected for historical, theoretical, or observed safety concerns (i.e., observed in clinical trials)\n•Attempts are made to obtain medical records for all primary AESI reports (serious* and non -serious)\n•CDC reviews records and abstracts clinically important information\n•AESIs may be added to or removed from the list as appropriate\n▪Secondary AESIs\n•Monitored via periodic (e.g., weekly) automated data tables\n•Can be added to primary AESI list if safety concerns identified\n* Based on the Code of Federal Regulations if one of the following is reported: death, life -threatening illness, hospitalization o r prolongation of hospitalization, \npermanent disability, congenital anomaly or birth defect16\nAESI after RSV vaccination\n▪Outcomes of general interest\n•Death\n▪Neurologic/neuroinflammatory conditions\n•Guillain -Barré syndrome (GBS), including Miller Fisher variant\n•Acute disseminated encephalomyelitis (ADEM)\n•Transverse myelitis (TM)\n•Chronic inflammatory demyelinating polyneuropathy (CIDP)\n▪Allergic reactions\n•Anaphylaxis\n▪Cardiac conditions\n•Atrial fibrillation\n•Other supraventricular tachycardias (SVT)▪Neurologic/neuroinflammatory conditions\n•Optic neuritis\n•Multiple sclerosis\n•Bell’s palsy\n•Encephalitis/Encephalomyelitis\n•Meningitis/Meningoencephalitis\n•Myelitis\n▪Other conditions\n•Vaccination errors\n•AEs following simultaneous administration with \nCOVID -19, inactivated influenza, or other adult \nvaccinesPrimary AESI Secondary AESI\n17\n8 participating medical \nresearch centers with \nvaccine safety experts*More information about clinical consults available at: : Clinical Immunization Safety \nAssessment (CISA) Project | CISA | Monitoring | Ensuring Safety | Vaccine Safety | CDCCISA \nClinical\nImmunization\nSafety\nAssessment \n(CISA) Project \n▪clinical consult services*\n▪clinical expertise for surveillance \n▪clinical research\n18\nU.S. reports to VAERS following respiratory syncytial virus (RSV) \nvaccination among adults ages ≥60 years  (as of February 16, 2024) \nVaccineDoses administered\n(as of Feb 2 –3, 2004)*Median age\n(IQR†), yearsFemale\nN (%)Non -serious\nN (%)Serious‡\nN (%)Total \nReports\nGSK (Arexvy) 6,587,912 72 (67 –77) 1,674 (67) 2,347 (93) 169 (7) 2,516\nPfizer ( Abrysvo ) 3,063,832 73 (68 –78) 618 (59) 954 (91) 91 (9) 1,045\nVaccine brand \nunknownNot applicable 73.5 (67 -78) 70 (55) 109 (85) 19 (15) 128\n Total 9,651,744 72 (67 –77) 2,362 (64) 3,410 (92) 279 (8) 3,689\n* Doses administered during August 4, 2023, through February 3, 2024, at medical offices from AMA’s list of physicians [Data source: Custom IQVIA Custom Medical Claims (Dx)] and during August 12, 2023, through \nFebruary 2, 2024, at retail pharmacies [Data source: Custom Longitudinal Prescription Claims ( LRx)]. IQVIA data do not include vaccinations administered at other medical settings such as public health clinics and \nother settings including workplaces and community locations. These represent projected doses. Based on a sample of retail pha rmacies and medical offices of a sample of AMA physicians, IQVIA projects doses \nadministered in all retail pharmacies and medical offices of all AMA physicians. \n† Interquartile range\n‡ Based on the Code of Federal Regulations if one of the following is reported: death, life -threatening illness, hospitalization or prolongation of hospitalization, permanent disability, congenital anomaly or birth defect\n19\nMost frequently reported MedDRA Preferred Terms* among reports to VAERS \nfollowing RSV vaccination among adults ages ≥60 years, by manufacturer  \n(as of February 16, 2024 )\nRankAll Reports\n(N=3,689)†,‡ n (%)Pfizer (Abrysvo)\n(N=1,045)† n (%)GSK (Arexvy)\n(N=2,516)† n (%)\n1 Pain in extremity 439 (12) Fatigue 120 (12) Pain in extremity 327 (13)\n2 Fatigue 432 (12) Headache 114 (11) Injection site pain 320 (13)\n3 Pain 414 (11) Pain in extremity 99 (10) Pain 305 (12)\n4 Injection site pain 408 (11) Pain 97 (9) Fatigue 290 (12)\n5 Headache 404 (11) Fever 95 (9) Headache 277 (11)\n6 Fever 353 (10) Arthralgia 86 (8) Injection site erythema 267 (11)\n7 Injection site erythema 338 (9) Injection site pain 81 (8) Fever 249 (10)\n8 Arthralgia 304 (8) Chills 75 (7) Arthralgia 210 (8)\n9 Erythema 255 (7) Nausea 71 (7) Erythema 193 (8)\n10 Injection site swelling 247 (7) Dizziness 70 (7) Injection site swelling 191 (8)\n* Medical Dictionary for Regulatory Activities Preferred Terms ( MedDRA Hierarchy | MedDRA )\n†Signs and symptoms are not mutually exclusive \n‡ Includes 128 reports with unknown RSV vaccine brand20\nMost frequently reported MedDRA Preferred Terms* among reports to VAERS \nfollowing RSV vaccination among adults ages ≥60 years (as of February 16, 2024 )\nRank MedDRA PT (not mutually exclusive) n (%)\n1 Dyspnoea 48 (17)\n2 Asthenia 47 (17)\n3 Fatigue 38 (14)\n4 Gait disturbance 35 (13)\n5 Fever 34 (12)\n6 Muscular weakness 33 (12)\n7 Nausea 31 (11)\n8 Guillain -Barré syndrome 30 (11)\n9 Intensive care 29 (10)\n10 Paraesthesia 29 (10)Serious reports†,‡ (N=279) Non -serious reports† (N=3,410)\nRank MedDRA PT (not mutually exclusive) n (%)\n1 Pain in extremity 416 (12)\n2 Injection site pain 395 (12)\n3 Fatigue 394 (12)\n4 Pain 388 (11)\n5 Headache 384 (11)\n6 Injection site erythema 333 (10)\n7 Fever 319 (9)\n8 Arthralgia 284 (8)\n9 Erythema 252 (7)\n10 Injection site swelling 245 (7)\n* Medical Dictionary for Regulatory Activities Preferred Terms ( MedDRA Hierarchy | MedDRA )\n†Includes 128  reports with unknown  RSV vaccine brand (109 non -serious and 19 serious) \n‡ Based on the Code of Federal Regulations if one of the following is reported: death, life -threatening illness, hospitalization o r prolongation of hospitalization, permanent disability, congenital anomaly or birth defect21\nReports* to VAERS of selected AESIs after RSV vaccination among adults \nages ≥60 years (as of February 16, 2024)\nConditionPfizer\n(Abrysvo )GSK\n(Arexvy )No brand\nname Total\nDeath 9 22 3 34\nGuillain -Barré syndrome (GBS) 18 16 1 35\nAcute disseminated\nencephalomyelitis (ADEM)1 0 1 2\nTransverse myelitis (TM) 1 2 0 3\nChronic inflammatory demyelinating\npolyneuropathy (CIDP)0 1 0 1\nAnaphylaxis 1 1 0 2\nAtrial fibrillation 15 38 5 58\nSupraventricular tachycardia (SVT) 1 2 0 3\nTotal 46 82 10 138▪On January 19, 2024, a data \nmining alert for \ndisproportional reporting was \ndetected in FDA Empirical  \nBayesian (EB) data mining for \nPfizer ( Abrysvo ) RSV vaccine \nand GBS\n▪No data mining alert for GSK \n(Arexvy ) RSV vaccine and GBS \nhas been detected to date\n▪EB data mining is product -\nspecific and analyzes product -\nspecific vaccine -adverse event \npairings compared to the \noverall VAERS database\n*Reports in this table include verified, \nunverified, ruled out and duplicate reports\n22\nReports to VAERS of Guillain -Barré syndrome (GBS) after respiratory \nsyncytial virus (RSV) vaccination among adults (as of February 16, 2024)\n▪23 verified* reports of GBS with symptom onset within \n42 days (all within 22 days) of RSV vaccination:\n•Pfizer ( Abrysvo ) (n=15), GSK ( Arexvy ) (n=8)\n•Median age: 71 years (IQR: 63,75 years)\n•1 report in a non -pregnant female patient aged 50s \nyears, received Pfizer ( Abyrsvo )\n•Median time to onset: 9 days (range 1,22 days**)\n•14 males, 9 females\n•None were pregnant\n•1 death; patient aged 70s years, male, received GSK ( Arexvy )Preliminary reports† of GBS\n(N=37)\nUnder review‡ \n(n=6)\nExcluded based upon \nmedical record review \n(n=7)¶\nVerified GBS by medical record review (n=23)* Based on VAERS report and medical record review and application of GBS definition in: Sejvar et al. Brighton \nCollaboration GBS Working Group. Guillain -Barré syndrome and Fisher syndrome: case definitions and guidelines \nfor collection, analysis, and presentation of immunization safety data. Vaccine. 2011;29(3):599 -612.\n† Includes reports identified through automated search and clinical review; all vaccinated Aug 29, 2023, through \nJan 5, 2024 \n‡ Awaiting medical records\n¶ Includes one report in a pregnant person who received Pfizer ( Abyrsvo ) RSV vaccine; patient did not meet clinical \ncriteria for Guillain -Barr é syndrome following review by independent experts in CISA, including neurologists\n** Includes one report after GSK ( Arexvy ) RSV vaccine with onset at 22 daysPfizer ( Abrysvo )\n(n=15)GSK ( Arexvy )\n(n=8)Verified GBS but \nexcluded due to onset \n>42 days (n=1)\n23\nReports to VAERS of Guillain -Barré syndrome after respiratory \nsyncytial virus (RSV) vaccination among adults (as of February 16, 2024)\n▪All 23 verified reports met Brighton Collaboration criteria for GBS*:\n•3 were Brighton level 1, 12 were Brighton level 2, and 8 were Brighton level 3\n•21 of 23 were also classified as GBS cases (Brighton level 1 -3) by at least one CISA neurologist†\n▪4 reports involving Pfizer ( Abrysvo ) RSV vaccine had respiratory symptoms within 4 weeks prior to GBS onset\n▪Other vaccines were given during same visit in 14 of the 23 GBS reports‡:\nPfizer ( Abrysvo ) RSV vaccine n=9\nOther vaccine N\n Bivalent mRNA COVID -19 (Pfizer -BioNTech) 3\n Bivalent mRNA COVID -19 (Moderna)\n 13-valent pneumococcal conjugate vaccine1\n aIIV4 (Fluad) 1\n Imovax rabies 1\n Tdap (Boostrix) 1\n Zoster (Shingrix) 1\n RIV4 (Flublok) 1GSK ( Arexvy ) RSV vaccine n=5\nOther vaccine N\n HD-IIV4 (Fluzone high -dose influenza)\n Bivalent mRNA COVID -19 (Pfizer -BioNTech)\n 20-valent pneumococcal conjugate vaccine1\n aIIV4 (Fluad) 1\n Covid -19 Moderna 2\n Covid -19 Moderna\n HD-IIV4 (Fluzone high -dose influenza)1\n* Sejvar et al. Guillain -Barré syndrome and Fisher syndrome: case definitions and guidelines for collection, analysis, and presentation of immun ization safety data. Vaccine . 2011;29(3):599 -612.\n† One GSK report (death report) (Brighton level 4 per CISA) and 1 Pfizer report aged ≥60 years (Brighton level 4 and 5 per CISA) were not classified as GBS by at least one CISA neurologist after review  \n‡ Other vaccines were given within 4 weeks of symptom onset and not during same visit in 4 of the 23 reports. 1 Pfizer report, Biv alent mRNA COVID -19 vaccine; 1 GSK report, adjuvanted influenza vaccine; \n1 GSK report, unspecified influenza vaccine; 1 GSK report, inactivated influenza vaccine and 20 -valent pneumococcal conjugate va ccine24\nReports to VAERS of other non -GBS neuroinflammatory conditions \nafter respiratory syncytial virus (RSV) vaccination* (as of February 16, 2024)\n▪Transverse myelitis (n=2)\n•1 report each after Pfizer ( Abrysvo )† and GSK ( Arexvy )‡\n▪Acute Disseminated Encephalomyelitis (n=3)\n•1 report after Pfizer ( Abrysvo )‡ and 2 reports after GSK ( Arexvy )¶\n▪Posterior reversible encephalopathy syndrome (n=1)\n•1 report after Pfizer ( Abrysvo )‡ \n▪Acute encephalitis (n=1)\n•1 report after Pfizer ( Abrysvo ) †\n* Sejvar et al. E ncephalitis, myelitis, and acute disseminated encephalomyelitis (ADEM): case definitions and guidelines for collection, analy sis, and presentation of immunization safety data. \nVaccine. 2007;25(31):5771 -92. ​\n† Pending medical records\n‡ Case  classified as listed diagnosis by at least one CISA neurologist\n¶ One case  classified as insufficient information to verify diagnosis by CISA neurologists; another case pending review of medical recor ds 25\nObserved VAERS reports and reporting rates of verified Guillain -Barré \nsyndrome (GBS) after respiratory syncytial virus (RSV) vaccination \namong adults ages ≥60 years\n* Based on VAERS report and medical record review and application of GBS definition in: Sejvar et al. Brighton Collaboration GBS Working Group. Guillain -Barré syndrome and Fisher syndrome: case \ndefinitions and guidelines for collection, analysis, and presentation of immunization safety data. Vaccine. 2011;29(3):599 -612.\n† Doses administered during August 4, 2023, through February 3, 2024, at medical offices from AMA’s list of physicians [Data source: Custom IQVIA Custom Medical Claims (Dx)] and during August 12, 2023, \nthrough February 2, 2024, at retail pharmacies [Data source: Custom Longitudinal Prescription Claims ( LRx)]. IQVIA data do not include vaccinations administered at other medical settings such as public \nhealth clinics and other settings including workplaces and community locations. These represent projected doses. Based on a s amp le of retail pharmacies and medical offices of a sample of AMA physicians, \nIQVIA projects doses administered in all retail pharmacies and medical offices of all AMA physicians. \n‡ Assumes complete person -time follow -up\n¶ Reporting rate  for Pfizer ( Abrysvo ) increases to 4.9if patient aged 50s years is included26Age group\n(years)Risk \nwindowRSV vaccineObserved verified\nGBS reports*\n(as of Feb 16, 2024)Doses\nadministered†\n(as of Feb 2 –3, 2024)Observed VAERS \nreporting rate \n(per million\ndoses admin)‡\n≥60 21-daysPfizer ( Abrysvo ) 14 3,063,832 4.6¶\nGSK ( Arexvy ) 7 6,587,912 1.1\n≥60 42-daysPfizer ( Abrysvo ) 14 3,063,832 4.6¶\nGSK ( Arexvy ) 8 6,587,912 1.2\nUsing estimated rate of chart confirmed GBS after mRNA COVID -19 vaccination \nin the Vaccine Safety Datalink (VSD) as a proxy for background rate*\n▪Safety monitoring of mRNA COVID -19 vaccines in the VSD did NOT  detect an increased risk of \nGBS associated with either of the mRNA COVID -19 vaccines\n•Therefore, the rate of GBS following mRNA COVID -19 vaccination can be used as a proxy for the \nbackground rate of GBS in a ‘vaccine -accepting’ population\n•This rate is appropriate because it is relatively current and all GBS cases were a priori chart reviewed\n•However, there are limitations (e.g., different populations, different time periods, different age groups)\n▪Estimated rate of confirmed cases of GBS in those 65+ years of age following mRNA COVID -19 \nprimary series vaccination in VSD\n•21-day risk interval : 3.4 (95% CI 1.2 –7.3) per 100,000 person -years\n•42-day risk interval : 4.5 (95% CI 2.4 –7.7) per 100,000 person -years\n▪Expected cases per 1 million RSV doses administered, assuming complete person -time \nfollow -up\n•21-day risk interval : 2.0 cases per million doses admin (range from 95% CI 0.7 –4.2)\n•42-day risk interval : 5.2 cases per million doses admin (range from 95% CI 2.8 –8.9)\n*Hanson et al. Incidence of Guillain -Barré Syndrome After COVID -19 Vaccination in the Vaccine Safety Datalink. JAMA Netw  Open. 2022;5(4):e228879 and VSD unpublished data.27\nObserved VAERS reports and reporting rates of verified Guillain -Barré \nsyndrome (GBS) after respiratory syncytial virus (RSV) vaccination among \nadults ages ≥60 years and estimated background rates\nAge group\n(years)Risk \nwindowRSV vaccineObserved verified\nGBS reports*\n(as of Feb 16, \n2024)Doses\nAdmin\n(as of Feb 2 –3, \n2024)†Observed VAERS  \nReporting rate \n(per million\ndoses admin)‡Estimated \nexpected rate \n(per million\ndoses admin) \nbased on VSD \ndata¶\n≥60 21-daysPfizer ( Abrysvo ) 14 3,063,832 4.6 2.0\n(95% CI 0.7 –4.2)GSK ( Arexvy ) 7 6,587,912 1.1\n≥60 42-daysPfizer ( Abrysvo ) 14 3,063,832 4.65.2\n(95% CI 2.8 –8.9)GSK ( Arexvy ) 8 6,587,912 1.2\n* Based on VAERS report and medical record review and application of GBS definition in: Sejvar et al. Brighton Collaboration GBS Working Group. Guillain -Barré syndrome and Fisher syndrome: case definitions \nand guidelines for collection, analysis, and presentation of immunization safety data. Vaccine. 2011;29(3):599 -612.\n† Doses administered during August 4, 2023, through February 3, 2024, at medical offices from AMA’s list of physicians [Data source: Custom IQVIA Custom Medical Claims (Dx)] and during August 12, 2023, \nthrough February 2, 2024, at retail pharmacies [Data source: Custom Longitudinal Prescription Claims ( LRx)]. IQVIA data do not include vaccinations administered at other medical settings such as public health \nclinics and other settings including workplaces and community locations. These represent projected doses. Based on a sample o f retail pharmacies and medical offices of a sample of AMA physicians, IQVIA \nprojects doses administered in all retail pharmacies and medical offices of all AMA physicians. \n‡ Assumes complete person -time follow -up\n¶ Background data (21 -day and 42 -day risk windows) on Guillain -Barré syndrome after COVID -19 vaccines from the vaccine safety data link (cases per million doses); estimate of background rate in a vaccine -\naccepting population and used as proxy because data from VSD did not detect an increased risk of GBS after mRNA COVID -19 vaccines (Source: Hanson et al. Incidence of Guillain -Barré syndrome After COVID -\n19 Vaccination in the Vaccine Safety Datalink. JAMA Netw  Open. 2022;5(4):e228879.) and VSD unpublished data28\nObserved VAERS reports and reporting rates of verified Guillain -Barré syndrome \n(GBS) after respiratory syncytial virus (RSV) vaccination among adults ages ≥60 \nyears compared to the VAERS reporting rate for COVID -19 vaccines\nAge group\n(years)RSV vaccineGBS reporting \nrate in VAERS\n(verified cases)\nper million\ndoses admin*\n≥60 Pfizer ( Abrysvo ) 4.6\n≥60 GSK ( Arexvy ) 1.1\n* Assumes complete person -time follow -up\n† Reporting rate for GBS (21 -day risk window) after mRNA Covid -19 vaccines from VAERS in persons aged ≥65 years during December 20 20-January 2022. Source: Abara  et al. Reports of \nGuillain -Barré syndrome After COVID -19 Vaccination in the United States. JAMA Netw  Open. 2023;6(2):e2253845. \n‡ An association between Ad26 and GBS was observed but not between GBS and mRNA COVID -19 vaccines\n21-day risk interval\n21-day risk interval†,‡\n29\nVaccine Safety Datalink (VSD)\n▪Established in 1990\n▪Collaborative project \nbetween CDC and 13 \nintegrated healthcare \norganizations\n▪Includes electronic health \ndata annually on ~13.5 \nmillion individuals across \nall sites which includes ~2.8 \nmillion adults aged 60 \nyears or older\n30\nObserved VSD GBS rates following RSV vaccination in adults \naged ≥60 years through December 30, 2023\n▪The VSD has identified 4 GBS cases within 1 -84 days of GSK ( Arexvy ) RSV vaccination; all 4 cases have \nundergone medical record review and have been adjudicated according to Brighton Criteria*\n \nGSK ( Arexvy ) Chart Confirmed Results – Brighton Levels 1, 2, or 3\n \n▪The 4th case, absent from the table above, was classified as Brighton Level 4 and is pending \nadditional medical record review\n▪Currently no cases of GBS have been observed within 1 –42 days after Pfizer ( Abrysvo ) RSV vaccination \nin VSD, but only ~10% of all RSV vaccinations in VSD have been with the Pfizer product\n▪VSD will continue to monitor the safety of RSV vaccines in adults aged ≥60 years and formal sequential \nsafety analysis will begin in March 2024 using a vaccinated concurrent comparison group (similar to \nCOVID -19 vaccine safety monitoring)\n31\n* Sejvar et al. Guillain -Barré syndrome and Fisher syndrome: case definitions and guidelines for collection, analysis, and prese ntation of immunization safety data. Vaccine . 2011;29(3):599 -612.Vaccine Risk window# GBS\ncases# vaccine\ndosesRate per million\ndoses admin\n(95% CI)Rate per 100,000 \nperson years\n(95% CI)\nGSK ( Arexvy ) 1-21 days 2 209,653 9.5 (1.2 –34.5) 16.6 (2.0 –59.9)\nGSK ( Arexvy ) 1-42 days 3 209,653 14.3 (3.0 –41.8) 12.4 (2.6 –36.4)\nSummary: Early post -licensure safety monitoring of \nRSV vaccines in adults aged ≥60 years \n▪Local and systemic symptoms (e.g., fatigue) were the most commonly reported adverse \nevents following either of the RSV vaccines\n▪Monitoring in VAERS indicates a higher -than -expected number of GBS reports following \nPfizer ( Abrysvo ) RSV vaccine, but VAERS is subject to the limitations of passive surveillance\n•GBS cases were observed in the pre -licensure clinical trials for both the Pfizer ( Abrysvo ) and GSK \n(Arexvy ) RSV vaccines and GBS is included as an adverse event in the labels of both vaccines\n▪Early data from VSD suggest the potential for an increased rate for GBS after GSK ( Arexvy ) \nRSV vaccine, but additional analyses are needed to further assess this potential risk; \ninsufficient doses of Pfizer ( Abrysvo ) RSV vaccine used in VSD to inform risk\n▪Monitoring  for GBS following RSV vaccines in FDA and CDC (VSD) population -based active \nsurveillance systems is in progress\n▪CDC and FDA will continue to monitor RSV vaccine safety in VAERS and CDC will continue to \nmonitor in V -safe\n32\nAcknowledgements\n▪CDC Immunization Safety Office\n•VAERS Team\n•V-safe Team\n•Clinical Immunization Safety Assessment (CISA) Project\n•Vaccine Safety Datalink (VSD)\n▪Food and Drug Administration\n•Office of Biostatistics and Pharmacovigilance, Center for Biologics Evaluation \nand Research\n▪National Center for Immunization and Respiratory Diseases\n•Coronavirus and Other Respiratory Viruses Division\n33\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the \nofficial position of the Centers for Disease Control and Prevention.", "summary": "Centers for Disease Control and Prevention National Center for Emerging and Zoonotic Infectious Diseases Post -licensure safety monitoring of respiratory  syncytial virus (RSV) vaccines in adults aged ≥60 years Tom Shimabukuro, MD, MPH, MBA On behalf of the Immunization Safety Office, CDC Advisory Committee on Immunization Practices (ACIP) February 29, 2024 Topics ▪Background ▪CDC vaccine safety monitoring for RSV vaccines in adults aged ≥60 years •V-safe •Vaccine Adverse Event Reporting…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-28-29-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-02-28-29/05-RSV-Adults-Shimabukuro-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 34}
{"title": "06 RSV Adults Lloyd  508", "content": "1\nPreliminary Analysis of Guillain-Barré Syndrome \n(GBS) following RSV Vaccination among adults 65 years and older\n \nDr. Patricia Lloyd, ScM PhD\nHealth Statistician\nOffice of Biostatistics and Pharmacovigilance\nCenter for Biologics Evaluation and Research\nU. S. Food & Drug Administration\nMEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)\nRespiratory Syncytial Virus (RSV) Vaccines, Adults \nFebruary 29, 2024\n2\nOutline\n•Study Methods\n•Statistical Analysis\n•Study Results\n•Limitations\n•Conclusion\n•Appendix\n3\nStudy Methods\nStudy ObjectiveTo evaluate preliminary rates of Guillain- Barré Syndrome (GBS) following one dose of either \nRSVPreF3+AS01 (AREXVY) or RSVPreF  (ABRYSVO) vaccine and to compare the observed \nrates of GBS to the historical control (expected) rates\nStudy Design Retrospective cohort analysis with a historical comparator group\nData SourcesCenters for Medicare & Medicaid Services (CMS) administrative claims and enrollment \ninformation derived from CMS Medicare Shared Systems Data (SSD) (Medicare Parts A, B, and D)\nStudy PopulationCMS Medicare Beneficiaries ages 65 years and older, enrolled in Medicare Fee- for-Service \n(FFS) (Parts A and B) and Medicare Part D on the date of the first observed RSV vaccination\nStudy Period•RSVPreF : May 31, 2023 – Dec 2, 2023\n•RSVPreF3+AS01: May 3, 2023 – Dec 2, 2023\nExposuresOne dose of either RSVPreF  or RSVPreF3+AS01 that occurred after RSV vaccine \nauthorization and prior to the data through date, i.e., Dec 2, 2023\nHealth Outcome GBS (Risk Window: 1- 42 days; Care Setting: Inpatient – primary position only)\n4\n•The expected number of outcomes are standardized by age and sex\n•The analyses are adjusted for observational delay based on estimates from \nhistorical data\n•Incidence Rate Ratios (IRRs) are calculated by dividing observed rates by expected rates; corresponding 95% confidence intervals (CIs) are provided\n•Estimation of GBS positive -predictive value (PPV) -adjusted rates is based on \nmultiple imputed datasets\n•Chart review, PPV for GBS: 71% (95% CI: 63%, 79%)*Statistical Analyses\n*Arya,D.P ., et al. Surveillance for Guillain -Barré syndrome after 2015- 2016 and 2016- 2017 influenza vaccination of Medicare \nbeneficiaries. Vaccine, 2019. 37(43): p. 6543- 6549.\n5\n020,00040,00060,00080,000100,000120,000140,000160,000Number of RSV Vaccinations\nCalendar WeekRSVPreF RSVPreF3+AS01RSV Vaccinations by Calendar Week and Vaccine Brand\nClaims delay\nData through date 02DEC2023.\n6\nResults \nIncidence Rate Ratio (IRR) and 95% Confidence Interval (CI) of GBS Following an RSV \nvaccination, stratified by age group and sex \nRed font indicates statistically significant elevation in GBS risk. Summary\n•A total of 2,061,602 RSV vaccine doses were \nobserved \n•RSVPreF : 682,267 doses\n•RSVPreF3+AS01 : 1,379,335 doses\n•GBS was observed for both vaccines post- RSV \nvaccination\n•RSVPreF : 13 cases \n•RSVPreF3+AS01: <11 cases\n•An elevated IRR was observed for GBS \nfollowing RSV vaccination \n•RSVPreF : 6.9 (95% CI: 3.7, 11.9) \n•RSVPreF3+AS01: 2.8 (95% CI: 1.3, 5.1)\n•Also observed was elevated risk by age groups and sex, but the number of cases were small by \nsubgroups (<5)RSV Vaccine \nExposureAge \nGroup \n(years)SexEligible \nVaccinesObserved \nEventsIncidence Rate \nRatio\n(IRR)IRR\n95% Confidence \nInterval (CI)\nRSVPreF Overall Overall 682,267 13 6.9 (3.7, 11.9)\nRSVPreF 65-74 Male 141,269 <11 5.8 (1.2, 17.0)\nRSVPreF 75-84 Male 121,913 <11 8.5 (2.3, 21.8)\nRSVPreF 85+ Male 28,091 <11 13.3 (0.3, 74.2)\nRSVPreF 65-74 Female 191,409 <11 4.9 (0.6, 17.8)\nRSVPreF 75-84 Female 154,152 <11 8.5 (1.8, 24.7)\nRSVPreF 85+ Female 45,433 <11 - --\nRSVPreF3+AS01 Overall Overall 1,379,335 <11 2.8 (1.3, 5.1)\nRSVPreF3+AS01 65-74 Male 287,780 <11 2.0 (0.2, 7.2)\nRSVPreF3+AS01 75-84 Male 246,852 <11 3.3 (0.7, 9.6)\nRSVPreF3+AS01 85+ Male 55,292 <11 - --\nRSVPreF3+AS01 65-74 Female 394,413 <11 3.8 (0.8, 11.0)\nRSVPreF3+AS01 75-84 Female 310,546 <11 2.9 (0.4, 10.6)\nRSVPreF3+AS01 85+ Female 84,452 <11 - --\n7\nResults – PPV-adjusted Analyses\nAdjusted IRR and 95% CI of GBS Following an RSV vaccination\nRed font indicates statistically significant elevation in GBS risk. \n*Adjusted estimate based on multiple imputation.**Accounts for claims delay and 1- 42 day risk window for GBS. The GBS rate per 1 million doses assuming a 1- 21 risk window: \nRSVPreF  12.5 (95% CI 3.4, 21.7); RSVPreF3+AS01, 5.0 (95% CI 0.8, 9.2).Summary\n•An elevated IRR was observed for GBS following \nRSVPreF  vaccination\n•6.9 (95% CI: 1.9, 12.0)\n•A non- statistically significant elevated IRR was \nobserved for GBS following RSVPreF3+AS01 vaccination\n•2.8 (95% CI: 0.5, 5.0)RSV Vaccine ExposureEligible \nVaccines IRRIRR*\n95% Confidence \nInterval (CI)GBS  Rate**\nper 1 million \ndoses95% CI**\nRSVPreF 682,267 6.9 (1.9, 12.0) 25.1 (6.7, 43.4)\nRSVPreF3+AS01 1,379,335 2.8 (0.5, 5.0) 10.0 (1.7, 18.3)\n•Adjusted GBS rates per 1 million doses:\n•RSVPreF : 25.1 ( 95% CI: 6.7, 43.4)\n•RSVPreF3+AS01: 10.0 ( 95% CI: 1.7, 18.3)\n•Multiple imputation was not successful in estimating IRR for age and sex subgroups due to the small \nnumber of cases\n•Medical charts for observed cases have been \nrequested and will be reviewed\n8\n•The observed vs. expected analysis utilizes aggregate historical rates rather \nthan individual historical persons as comparators, increasing the potential for \nconfounding and bias\n•Health outcomes are identified by International Classification of Disease – 10th \nRevision – Clinical Modification (ICD- 10-CM) diagnosis codes in administrative \nclaims databases, hence are subject to outcome misclassification\n•GBS is a rare outcome, the number of cases are small, the uncertainty is high, therefore it poses a challenge for verification of a potential signalLimitations\n9\n•An elevated risk of GBS was observed \nfollowing both RSV vaccines \n•RSVPreF  (n=13 cases) and \nRSVPreF3+AS01 (n<11 cases)\n•Results did not remain statistically significant for RSVPreF3+AS01 when adjusting for the PPV\n•Safety monitoring following RSV vaccination using a self -controlled case \nseries design is planned and will provide more conclusive evidence of the potential risks following RSV vaccinationConclusions\nhttps://bestinitiative.org/wp -content/uploads/2023/12/BEST_RSV_Safety_Older_Adults_2023- 2024.pdf\n10\nAcknowledgments\n•Steven Anderson\n•Richard Forshee\n•Henry Zhang\n•Joann Gruber\n•Carla Zelaya\n•Tainya Clarke\n•FDA BEST Partners: \n–Acumen, CMS\nwww.bestinitiative.org\nQuestions?\n11", "summary": "1 Preliminary Analysis of Guillain-Barré Syndrome  (GBS) following RSV Vaccination among adults 65 years and older   Dr. Patricia Lloyd, ScM PhD Health Statistician Office of Biostatistics and Pharmacovigilance Center for Biologics Evaluation and Research U. S. Food & Drug Administration MEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP) Respiratory Syncytial Virus (RSV) Vaccines, Adults  February 29, 2024 2 Outline •Study Methods •Statistical Analysis •Study Results…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-28-29-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-02-28-29/06-RSV-Adults-Lloyd--508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 11}
{"title": "07 RSV Adults Melgar 508", "content": "Centers for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nRSV Vaccination in Older Adults:\nBenefit -Risk Discussion\nMichael Melgar , MD\nLauren Roper, MPH\nAdvisory Committee on Immunization Practices\nFebruary 29, 2024\nThere are two RSV vaccines approved in the United States \nand recommended for adults aged ≥60 years, using shared \nclinical decision -making.\nSlide credit: https://stacks.cdc.gov/view/cdc/108883  \nEstimated benefits  \nof RSV vaccination \n(single dose) with \nGSK’s Arexvy  and \nPfizer’s Abrysvo , \nstratified by agePotential risk  of \nGuillain -Barre \nsyndrome (GBS) after \nRSV vaccination with \nGSK’s Arexvy  and \nPfizer’s Abrysvo\n2\n▪Estimated benefits\n–Estimated numbers of preventable RSV illnesses over  two \nconsecutive seasons , per 1 million vaccine doses administered to \nadults 60 years and older1\n•Outpatient visits, hospitalizations, intensive care unit (ICU) \nadmissions, in -hospital deaths\n–Informed by published incidence rates, RSV surveillance data \nfrom CDC, and estimated vaccine efficacy from clinical trials\n▪Potential risk\n–Informed by rate of GBS per 1 million vaccine doses \nadministered to adults 60 years and older1 observed in FDA \nanalysis of data from the FDA -CMS partnership2\n–Preliminary data did not permit estimation of attributable (i.e., \nexcess) risk, so observed rates are also compared with rates \nexpected from backgroundOverview of comparisons\n1. This analysis assumes 100% uptake of RSV vaccine, with a single dose, in a cohort of 1 million older adults.\n2. Analysis of administrative claims data using a 42 -day risk interval, adjusted for delays in claims data. https://bestinitiative.org/wp -content/uploads/2024/01/BEST_RSV_Safety_Older_Adults_2023 -2024.pdf  \n3\nEstimated age distribution of national RSV -associated hospitalizations, ICU admissions, and in -\nhospital deaths among adults ≥18 years, RSV -NET, 2022 –2023, compared with U.S. population\nUnpublished data. Underlying rates are adjusted using multipliers for the frequency of RSV testing during each season and for  the sensitivity of RSV diagnostic tests. Estimates \nfrom 2022 -2023 are preliminary. These estimates use the same multipliers as for 2019 -2020.\n*As of 2022. https://www.census.gov/popclock/  42.9%\n37.1%\n58.0%\n9.2%23.9%\n26.8%\n22.8%\n13.0%20.4%\n22.6%\n11.3%\n24.1%12.8%\n13.6%\n7.9%\n53.7%\n0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%Hospitalizations\nICU admissions\nIn-hospital deaths\nU.S. Adult Population*≥75 65-74 50-64 18-49\nU.S. Adult Population *Age group, years:\n4\n0100200300400500600\n2016-17 2017-18 2018-19 2019-20 2020-21 2021-22** 2022-23**Annual RSV -associated hospitalizations \nper 100,000 population 18-49 50-54 55-59 60-64 65-69 70-74 75-79 ≥80 \nUnpublished data. Rates are adjusted using multipliers for the frequency of RSV testing during each season and the sensitivit y of RSV diagnostic tests.\n*Estimated rates exclude recorded hospitalizations among pregnant adults.\n**Estimates from 2021 -2022 and 2022 -2023 are preliminary. These estimates use the same multipliers as for 2019 -2020.\nhttps://www.cdc.gov/rsv/research/rsv -net/index.html  Estimated annual RSV -associated hospitalization  rates per 100,000 adults* \naged ≥18 years by age group and year, RSV -NET, 2016 –17 to 2022 –23\nAge group, years:\n5\n0100200300400500600\n2016-17 2017-18 2018-19 2019-20 2020-21 2021-22** 2022-23**Annual RSV -associated hospitalizations \nper 100,000 population 60-64 65-69 70-74 75-79 ≥80 Inputs : Estimated annual RSV -associated hospitalization  rates per 100,000 \nadults* aged ≥60 years by age group and year, RSV -NET, 2016 –17 to 2022 –23\nUnpublished data. Rates are adjusted using multipliers for the frequency of RSV testing during each season and the sensitivit y of RSV diagnostic tests.\n*Estimated rates exclude recorded hospitalizations among pregnant adults.\n**Estimates from 2021 -2022 and 2022 -2023 are preliminary. These estimates use the same multipliers as for 2019 -2020.\nhttps://www.cdc.gov/rsv/research/rsv -net/index.html  Age group, years:\n6\n▪Over the same surveillance seasons \n(2016 -17 to 2019 -20, and 2022 -23):\n–Calculated the proportions of hospitalized \nadults in each age group who\n•Were admitted to ICU\n•Experienced in -hospital death\n–Applied these proportions to the estimated \nhospitalization rates*\n–Estimated population -based rates of ICU \nadmission and in -hospital deathInputs : Estimated annual rates of RSV -associated ICU admission and \nin-hospital death per 100,000 adults aged ≥60 years (RSV -NET)\n*Unpublished data. Rates are adjusted using multipliers for the frequency of RSV testing during each season and the sensitivi ty of RSV diagnostic tests.\nEstimated rates exclude recorded hospitalizations among pregnant adults.\nEstimates from 2022 -2023 are preliminary. These estimates use the same multipliers as for 2019 -2020.\nhttps://www.cdc.gov/rsv/research/rsv -net/index.html  \n7\n05001,0001,5002,0002,500\n18-49 50-64 ≥65 Annual RSV -associated outpatient visits \nper 100,000 population \nAge (years)Inputs : Estimated annual rates of RSV -associated outpatient visits  per 100,000 \nadults aged ≥18 years , meta -analysis of active surveillance studies, United States\nIndustry -sponsored (Pfizer): McLaughlin JM, Khan F, Begier  E, et al. Rates of Medically Attended RSV Among US Adults: A Systematic Review and Meta -\nanalysis. Open forum infectious diseases 2022 Jul; 9(7):ofac300. https://doi.org/10.1093/ofid/ofac300  \n8\nInputs : Summary of annual rates of RSV -associated illness\n1. Industry -sponsored (Pfizer): McLaughlin JM, Khan F, Begier  E, et al. Rates of Medically Attended RSV Among US Adults: A Systematic Review and Meta -analysis. Open \nforum infectious diseases 2022 Jul; 9(7):ofac300. https://doi.org/10.1093/ofid/ofac300  \n2. CDC RSV -NET data from surveillance seasons: 2016 -17 to 2019 -20 and 2022 -23. Values are based upon the average burden -adjusted ra tes and 95% confidence intervals \nover those five seasons. Unpublished data.  https://www.cdc.gov/rsv/research/rsv -net/index.html  \n3. Kujawski SA, Whitaker M, Ritchey MD, et al. Rates of respiratory syncytial virus (RSV) -associated hospitalization among adults w ith congestive heart failure -United States, \n2015 -2017. PLoS  One. 2022 Mar 9;17(3):e0264890. https://doi.org/10.1371/journal.pone.0264890  \n4. Industry -sponsored (Pfizer): Onwuchekwa C, Moreo LM, Menon S, et al.  Underascertainment  of Respiratory Syncytial Virus Infection in Adults Due to Diagnostic Testing \nLimitations: A Systematic Literature Review and Meta -analysis. The Journal of Infectious Diseases. 2023 July; 228(2): 173 –184. https://doi.org/10.1093/infdis/jiad012  Outcome Values\nOutpatient visits Published incidence rates and 95% confidence intervals.1 \nHospitalizations RSV -NET2; age -dependent rates and 95% confidence intervals are based on laboratory -\nconfirmed RSV infections among hospitalized adults detected through clinician -driven testing, \nand are adjusted for the frequency of RSV testing among adults hospitalized with respiratory \nillness and for the sensitivity of diagnostic tests (burden adjustment).3 Assumed test sensitivity \nincorporates recent literature showing increased diagnostic yield from multiple specimen \ntypes, relative to nucleic acid testing of nasopharyngeal swab alone.4 Input values are taken as \nthe mean burden -adjusted rates over five RSV seasons (2016 -17 to 2019 -20, and 2022 -23).\nICU admissions Mean age -dependent rates and 95% confidence intervals of RSV -associated ICU admission  \nfrom RSV -NET over five seasons2\nDeaths\n(in-hospital only)Mean age -dependent rates and 95% confidence intervals of RSV -associated in -hospital deaths \nfrom RSV -NET over five seasons2\n9\nOutcome (RSV -Associated) Arexvy , GSK1\nVE (95% CI)Abrysvo , Pfizer2\nVE (95% CI)\nSeason 1\n(months 0 -7 \npost -injection)Season 2\n(months 13 -18 \npost -injection )3Season 1\n(months 0 -7 \npost -injection)Season 2\n(months 8 -14 \npost -injection )3\nOutpatient visits4\nTrial efficacy against medically -attended \nRSV ARI79.0% \n(54.3, 91.5)27.8% \n(0, 60.4)65.2% \n(36.0, 82.0)55.0% \n(0, 82.0)\nHospitalizations, ICU Admissions, \nand In -hospital Deaths \nTrial efficacy against medically -attended \nRSV LRTD/LRTI87.5% \n(58.9, 97.6)552.9%\n(0, 81.2)584.6%\n(32.0, 98.3)675.0%\n(0, 97.4)6Inputs : Vaccine Efficacy (VE)\nPoint estimates were used in this analysis. Uncertainty in vaccine efficacy was not incorporated into uncertainty in estimate d preventable outcomes.\nRef (Slide 18): https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2023 -06-21-23/05 -RSV -Adults -Ortega -Sanchez -508.pdf\n1 GSK Phase 3 Trial; interim analysis 2023; CDC -calculated vaccine efficacy in participants ages ≥60 years\n2 Pfizer Phase 3 Trial; interim analysis 2023; CDC -calculated vaccine efficacy in participants ages ≥60 years\n3 Efficacy estimates are not directly comparable. Clinical trials used different outcome definitions and the follow up time in differed substantially across \ntrials. Further, efficacy estimates are associated with substantial uncertainty.\n4 CDC -calculated VE against medically -attended RSV acute respiratory illness (ARI)\n5 CDC -calculated VE against medically -attended RSV lower respiratory tract disease (LRTD)\n6 CDC -calculated VE against medically -attended RSV lower respiratory tract illness (LRTI) with at least 3 lower respiratory sympto ms10\nWeekly rates of RSV -associated hospitalization,* all ages, \nRSV -NET, October 2018 –February 2024\n*RSV -NET hospitalization data are preliminary and subject to change as more data becomes available.\nRates have not been adjusted for testing practices and underestimate actual rates of RSV -associated hospitalizations, as not all  people hospitalized with respiratory illness are \ntested for RSV. In addition, clinician -directed RSV testing practices may have changed over time and may differ by disease sever ity, age, and/or racial and ethnic group of \npatients; trends in RSV -associated hospitalization rates across seasons should be interpreted with caution.\nFor more information on RSV -NET, please visit https://www.cdc.gov/rsv/research/rsv -net/index.html . 2018 -192019 -20\n2020 -212021 -222022 -23\n2023 -24\n0123456\n40414243444546474849505152123456789101112131415161718192021222324252627282930313233343536373839\nOct Nov Dec Jan Feb Mar Apr May Jun Jul Aug SepWeekly RSV -associated hospitalizations \nper 100,000 population\nMonth and MMWR Week\n11\n▪Clinical trials of both vaccines under -enrolled adults 75 years \nand older and were under -powered to estimate vaccine \nefficacy in this age subgroup.\n▪Aging results in lowered immune responsiveness \ncharacterized by impairments in both innate and adaptive \nimmunity (immune senescence).*\n▪Adults 75 years and older might experience reduced VE \nagainst all outcomes, compared with adults ages 60 –74 years.\n▪There are no data yet available from post -licensure \nobservational effectiveness studies to estimate protection \namong adults aged ≥75 years.Inputs: Vaccine Efficacy (VE), sensitivity analysis\nAssumed VE among adults aged ≥75 years is reduced by half , compared with adults aged 60 –74 years\n*Stephens LM, Varga SM. Considerations for a Respiratory Syncytial Virus Vaccine Targeting an Elderly Population. Vaccines (B asel). 2021 Jun 9;9(6):624. \nhttps://doi.org/10.3390/vaccines9060624  \n12\nOutcome (RSV -Associated) Arexvy , GSK1\nVE (95% CI)Abrysvo, Pfizer2\nVE (95% CI)\nSeason 1\n(months 0 -7 \npost -injection)Season 2\n(months 13 -18 \npost -injection )3Season 1\n(months 0 -7 \npost -injection)Season 2\n(months 8 -14 \npost -injection )3\nOutpatient visits3\nTrial efficacy against medically -attended \nRSV ARIAges 60 –74 yrs: \n79.0% \nAges ≥75 yrs: \n39.5%Ages 60 –74 yrs: \n27.8% \nAges ≥75 yrs: \n13.9%Ages 60 –74 yrs: \n65.2%\nAges ≥75 yrs: \n32.6%Ages 60 –74 yrs: \n55.0% \nAges ≥75 yrs: \n27.5%\nHospitalizations, ICU Admissions, \nand In -hospital Deaths \nTrial efficacy against medically -attended \nRSV LRTD/LRTIAges 60 –74 yrs: \n87.5%4\nAges ≥75 yrs: \n43.8%Ages 60 –74 yrs: \n52.9%4\nAges ≥75 yrs: \n26.5%Ages 60 –74 yrs: \n84.6%5\nAges ≥75 yrs: \n42.3%Ages 60 –74 yrs: \n75.0%5\nAges ≥75 yrs: \n37.5%Inputs: Vaccine Efficacy (VE), sensitivity analysis\n13Point estimates were used in this analysis. Uncertainty in vaccine efficacy was not incorporated into uncertainty in estimate d preventable outcomes.\nRef (Slide 18): https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2023 -06-21-23/05 -RSV -Adults -Ortega -Sanchez -508.pdf\n1 GSK Phase 3 Trial; interim analysis 2023; CDC -calculated vaccine efficacy in participants ages ≥60 years\n2 Pfizer Phase 3 Trial; interim analysis 2023; CDC -calculated vaccine efficacy in participants ages ≥60 years\n3 Efficacy estimates are not directly comparable. Clinical trials used different outcome definitions and the follow up time in differed substantially across trials. Further, efficacy \nestimates are associated with substantial uncertainty.\n4 CDC -calculated VE against medically -attended RSV acute respiratory illness (ARI)\n5 CDC -calculated VE against medically -attended RSV lower respiratory tract disease (LRTD)\n6 CDC -calculated VE against medically -attended RSV lower respiratory tract illness (LRTI) with at least 3 lower respiratory sympto ms\nResults: Estimated Benefits\nPer 1 million vaccine doses administered\nEstimated RSV -Associated Outcomes* Preventable over 2 RSV Seasons \nper 1 Million Vaccine Doses Administered to Adults Aged ≥60 Years\n*Ranges of preventable outcomes were calculated using published 95% confidence intervals (outpatient only) and adjusted 95% confidence interval of \nRSV-associated incidence of the outcome observed in RSV -NET. Uncertainty in vaccine efficacy was not incorporated into ranges of  preventable outcomes.120 450 2,400 \n -  1,000  2,000  3,000  4,000  5,000140 520 2,700 \n -  1,000  2,000  3,000  4,000  5,000Outpatient visits\nHospitalizations\nICU Admissions\nIn-hospital Deaths//23,000Arexvy  (GSK) Abrysvo  (Pfizer)\n\\\\26,000\n15\nEstimated RSV -Associated Outcomes* Preventable over 2 RSV Seasons  \nper 1 Million Vaccine Doses Administered,  Arexvy  (GSK)\n350 870 6,000 \n170 660 3,200 \n86 390 1,900 \n66 340 1,500 \n41 260 1,100 \n -  1,000  2,000  3,000  4,000  5,000  6,000  7,000  8,000  9,000  10,00060-64 years\n65-69 years\n70-74 years\n75-79 years\n≥80 yearsHospitalizations\nICU Admissions\nIn-Hospital Deaths\n*Ranges of preventable outcomes were calculated using published 95% confidence intervals (outpatient only) and adjusted 95% confidence interval of \nRSV-associated incidence of the outcome observed in RSV -NET. Uncertainty in vaccine efficacy was not incorporated into ranges of  preventable outcomes.16\n//  18,000\n//  24,000\n//  24,000\n//  24,000\n//  24,000\n//  23,000\n175 435 3,000 \n85 330 1,600 \n86 390 1,900 \n66 340 1,500 \n41 260 1,100 \n -  1,000  2,000  3,000  4,000  5,000  6,000  7,000  8,000  9,000  10,00060-64 years\n65-69 years\n70-74 years\n75-79 years\n≥80 yearsHospitalizations\nICU Admissions\nIn-Hospital DeathsSensitivity analysis:\nVaccine efficacy reduced by \nhalf among adults ≥75 yearsEstimated RSV -Associated Outcomes* Preventable over 2 RSV Seasons  \nper 1 Million Vaccine Doses Administered,  Arexvy  (GSK)\n*Ranges of preventable outcomes were calculated using published 95% confidence intervals (outpatient only) and adjusted 95% confidence interval of \nRSV-associated incidence of the outcome observed in RSV -NET. Uncertainty in vaccine efficacy was not incorporated into ranges of  preventable outcomes.17\nEstimated RSV -Associated Outcomes* Preventable over 2 RSV Seasons  \nper 1 Million Vaccine Doses Administered,  Abrysvo  (Pfizer)\nHospitalizations\nICU Admissions\nIn Hospital Deaths\n400 990 6,800 \n200 750 3,600 \n98 440 2,200 \n75 380 1,700 \n46 300 1,200 \n0 1,000 2,000 3,000 4,000 5,000 6,000 7,000 8,000 9,000 10,00060-64 years\n65-69 years\n70-74 years\n75-79 years\n≥80 years\n*Ranges of preventable outcomes were calculated using published 95% confidence intervals (outpatient only) and adjusted 95% confidence interval of \nRSV-associated incidence of the outcome observed in RSV -NET. Uncertainty in vaccine efficacy was not incorporated into ranges of  preventable outcomes.18\nHospitalizations\nICU Admissions\nIn Hospital Deaths\n200 495 3,400 \n100 375 1,800 \n98 440 2,200 \n75 380 1,700 \n46 300 1,200 \n0 1,000 2,000 3,000 4,000 5,000 6,000 7,000 8,000 9,000 10,00060-64 years\n65-69 years\n70-74 years\n75-79 years\n≥80 yearsSensitivity analysis:\nVaccine efficacy reduced by \nhalf among adults ≥75 yearsEstimated RSV -Associated Outcomes* Preventable over 2 RSV Seasons  \nper 1 Million Vaccine Doses Administered,  Abrysvo  (Pfizer)\n*Ranges of preventable outcomes were calculated using published 95% confidence intervals (outpatient only) and adjusted 95% confidence interval of \nRSV-associated incidence of the outcome observed in RSV -NET. Uncertainty in vaccine efficacy was not incorporated into ranges of  preventable outcomes.19\n▪23,000 (17,000 –28,000)\n▪2,400 (1,800 –3,700)​\n▪450 (350 –690)​\n▪120 (94 –190)Summary:\nEstimated preventable RSV -associated outcomes varies by age and incidence of the outcome\nArexvy  (GSK)\n▪26,000 (19,000 –32,000)\n \n▪2,700 (2,100 –4,200)​ \n▪520 (400 –780)​ \n▪140 (110 –210)Abrysvo  (Pfizer)\nOutpatient visits\nHospitalizations\nICU admissions\nIn-hospital deaths▪Estimated number of outcomes preventable over 2 RSV seasons \nper 1 million doses administered were similar between vaccine products:\nRanges of preventable outcomes were calculated using published 95% confidence intervals (outpatient only) and adjusted 95% confidence interval of R SV-\nassociated incidence of the outcome observed in RSV -NET. Uncertainty in vaccine efficacy was not incorporated into ranges of preventable outcomes.20\nPotential Risk of Guillain -Barre syndrome (GBS)\nPer 1 million vaccine doses administered\n▪Claims -based ascertainment of GBS events using administrative data\n–GBS cases observed after RSV vaccination during a 42-day risk interval2, adjusted for delays in claims data\n–Adjustment for positive -predictive value of diagnostic codes in identifying chart -confirmed GBS\n▪GSK Arexvy : 10 GBS cases (95% CI 2 –18) per 1 million doses administered\n▪Pfizer Abrysvo : 25 GBS cases (95% CI 7 –43) per 1 million doses administered\n▪Expected cases based on historical GBS background rate from 2022:\n–5 GBS cases per 1 million doses administered3\n–Historical background rate may not be applicable to persons electing to receive RSV vaccination using \nshared clinical decision -making. On average, recipients of each of the two vaccines may be at different \nbaseline risk of GBS. More robust analysis, such as a self -controlled case series, is needed to confirm and \nquantify a risk of Guillain -Barre syndrome after RSV vaccination.FDA active surveillance through partnership with CMS,\nMedicare beneficiaries ages ≥65 years1, May –December 2023\nAbbreviations: CI = confidence interval, CMS = Centers for Medicare & Medicaid Services, FDA = U.S. Food and Drug Administrat ion, GBS = Guillain -Barre syndrome\n1.Must have been enrolled in Medicare Parts A, B and D. Must not have had a diagnostic code for GBS in the 365 days preceding v accination.\n2.Due to delays in claims data, not all participants have accrued 42 days of effective follow up time. GBS observation rates pe r 1 million doses over a 21-day risk interval \nwere also calculated ( GSK Arexvy : 5 cases [95% CI 1 –9], Pfizer Abrysvo : 13 cases [95% CI 3 –22]).\n3.The lower and upper bounds of the 95% confidence interval for the expected cases both round to 5. With additional precision: 5.06 expected GBS cases (95% CI 4.76 – \n5.38) per 1 million doses administered to adults ages 65 years and older. 22\nEstimated Benefits and \nPotential Risk\nPer 1 million vaccine doses administered\nPer 1 Million Vaccine Doses Administered to Adults Aged ≥60 Years:\n1.Range of outcomes avertable was calculated using published 95% confidence intervals (outpatient only) and adjusted 95% confid ence interval of RSV -associated incidence of the outcome observed in RSV -NET\n2.Includes GBS cases in a 42 -day risk interval post -RSV-vaccination, adjusted for claims delay, a mong beneficiaries ≥65 with Parts A, B, and D coverage who did not have a GBS claim in the 365 days before \nvaccination. Rates of GBS identified by inpatient claims data are decreased by 29% to account for the positive predictive val ue of diagnostic codes in identifying chart -confirmed GBS cases.\n3.Background GBS rate (4.4 cases per 100,000 person -years) from 2022 CMS data among Medicare beneficiaries 65 years and older with  Parts A, B, and D coverage and without a GBS claim in the 365 days \nbefore January 1, 2022. Rates of GBS identified by inpatient claims data are decreased by 29% to account for the positive pre dictive value of diagnostic codes in identifying chart -confirmed GBS cases.Estimated RSV -Associated Outcomes1 Preventable over 2 RSV Seasons  vs. potential cases of GBS\n(positive predictive value -adjusted  rate of GBS claims in FDA -CMS partnership data, 42 -day risk interval2)\nBy comparison, 5 GBS cases would be expected from background over the 42 -day risk interval3.\nHistorical background rate may not apply to adults electing to receive RSV vaccination using shared clinical decision -making. On  average, recipients of each of the two \nvaccines may be at different baseline risk of GBS. More robust analysis, such as a self -controlled case series, is needed to con firm and quantify a risk of GBS.10 (95% CI  2–18) cases of GBS 25 (95% CI 7–43) cases of GBS\n1.Range of outcomes avertable was calculated using published 95% confidence intervals (outpatient only) and adjusted 95% confid ence interval of RSV -associated incidence of the outcome observed in RSV -NET\n2.Includes GBS cases in a 42 -day risk interval post -RSV-vaccination, adjusted for claims delay, a mong beneficiaries ≥65 with Parts A, B, and D coverage who did not have a GBS claim in the 365 days before \nvaccination. Rates of GBS identified by inpatient claims data are decreased by 29% to account for the positive predictive val ue of diagnostic codes in identifying chart -confirmed GBS cases.\n3.Background GBS rate (4.4 cases per 100,000 person -years) from 2022 CMS data among Medicare beneficiaries 65 years and older with  Parts A, B, and D coverage and without a GBS claim in the 365 days \nbefore January 1, 2022. Rates of GBS identified by inpatient claims data are decreased by 29% to account for the positive pre dictive value of diagnostic codes in identifying chart -confirmed GBS cases.Estimated RSV -Associated Outcomes1 Preventable over 2 RSV Seasons  vs. potential cases of GBS\n(positive predictive value -adjusted  rate of GBS claims in FDA -CMS partnership data, 42 -day risk interval2)\nBy comparison, 5 GBS cases would be expected from background over the 42 -day risk interval3.\nHistorical background rate may not apply to adults electing to receive RSV vaccination using shared clinical decision -making. On  average, recipients of each of the two \nvaccines may be at different baseline risk of GBS. More robust analysis, such as a self -controlled case series, is needed to con firm and quantify a risk of GBS.10 (95% CI  2–18) cases of Guillain -Barre syndromePer 1 Million GSK Arexvy  Doses Administered to Older Adults:\n60–64 yrs 65–69 yrs 70–74 yrs 75–79 yrs ≥80 yrs\nHospitalizations \npreventable1,100 1,500 1,900 3,200 6,000\nICU admissions \npreventable260 340 390 660 870\nIn-hospital deaths \npreventable41 66 86 170 350\n25\n1.Range of outcomes avertable was calculated using published 95% confidence intervals (outpatient only) and adjusted 95% confid ence interval of RSV -associated incidence of the outcome observed in RSV -NET\n2.Includes GBS cases in a 42 -day risk interval post -RSV-vaccination, adjusted for claims delay, a mong beneficiaries ≥65 with Parts A, B, and D coverage who did not have a GBS claim in the 365 days before \nvaccination. Rates of GBS identified by inpatient claims data are decreased by 29% to account for the positive predictive val ue of diagnostic codes in identifying chart -confirmed GBS cases.\n3.Background GBS rate (4.4 cases per 100,000 person -years) from 2022 CMS data among Medicare beneficiaries 65 years and older with  Parts A, B, and D coverage and without a GBS claim in the 365 days \nbefore January 1, 2022. Rates of GBS identified by inpatient claims data are decreased by 29% to account for the positive pre dictive value of diagnostic codes in identifying chart -confirmed GBS cases.Estimated RSV -Associated Outcomes1 Preventable over 2 RSV Seasons  vs. potential cases of GBS\n(positive predictive value -adjusted  rate of GBS claims in FDA -CMS partnership data, 42 -day risk interval2)\nBy comparison, 5 GBS cases would be expected from background over the 42 -day risk interval3.\nHistorical background rate may not apply to adults electing to receive RSV vaccination using shared clinical decision -making. On  average, recipients of each of the two \nvaccines may be at different baseline risk of GBS. More robust analysis, such as a self -controlled case series, is needed to con firm and quantify a risk of GBS.25 (95% CI  7–43) cases of Guillain -Barre syndromePer 1 Million Pfizer Abrysvo  Doses Administered to Older Adults:\n60–64 yrs 65–69 yrs 70–74 yrs 75–79 yrs ≥80 yrs\nHospitalizations \npreventable1,200 1,700 2,200 3,600 6,800\nICU admissions \npreventable300 380 440 750 990\nIn-hospital deaths \npreventable46 75 98 200 400\n26\n▪We assumed optimal timing of vaccination immediately before onset of RSV season.\n▪We assumed that the real -world vaccine effectiveness is equal to point estimate of vaccine \nefficacy observed in the phase 3 clinical trials.\n–Assumed vaccine effectiveness against hospitalization was equal to vaccine efficacy against medically \nattended RSV -associated lower respiratory tract disease from clinical trials\n–Did not incorporate uncertainty in trial efficacy estimates. However, in preliminary analyses, uncertainty \nin RSV incidence resulted in wider ranges of preventable outcomes than uncertainty in efficacy.\n▪Clinical trials were performed largely in community dwelling older adults and may not be \ngeneralizable to all adults 60+ in the U.S. \n▪RSV -NET represents ~9% of the United States and hospitalization rates observed in RSV -NET \nmay not be generalizable to the U.S.\n▪Benefits of a single dose of RSV vaccination may continue to accrue beyond 2 years.\n▪RSV -NET does not currently estimate out -of-hospital deaths, resulting in an under -estimate of \npotentially vaccine -preventable deaths.\n▪Benefits may be greater for subgroups of adults at increased risk of severe RSV illness.Limitations (estimation of benefits) \n27\n▪GBS rates were calculated using a small number of events observed after RSV \nvaccination, resulting in high uncertainty.\n▪A background rate of GBS was not subtracted from the observed rate.\n–The historical background rate from CMS used as a comparator may not apply to adults receiving RSV \nvaccination using shared clinical decision -making; subject to confounding and bias.\n▪Older adults receiving each of the two vaccine products may have different prevalence \nof chronic medical conditions or other risk factors and may therefore have different \nbaseline risk of GBS.\n▪GBS was identified by diagnostic codes in administrative data and may be subject to \ncoding errors.\n▪Not all cases of GBS occurring after RSV vaccination may have received a diagnostic \ncode.Limitations (estimation of risk) \n28\n▪From a population perspective, the estimated benefits of RSV vaccination outweigh \nthe potential risk of GBS in adults 60 years and older.\n▪Estimated benefits of RSV vaccination vary by age group and RSV incidence.\n▪Estimated benefits likely also vary by individual -level risk of severe RSV disease and by \ntiming of vaccination relative to the RSV season.\n▪There is substantial uncertainty in estimates of both benefit and risk.\n▪The benefit and risk assessment will be updated as additional data become available:\n–Results from additional vaccine safety studies\n–Additional efficacy follow -up time from clinical trials\n–Vaccine effectiveness from post -licensure observational studies, including effectiveness against more \nsevere clinical outcomes \n–RSV disease burden among subgroups of older adults at increased risk of severe RSV diseaseSummary\n29\n▪Lauren Roper\n▪Amadea Britton\n▪Dani Moulia\n▪Megan Wallace\n▪Katherine Fleming -Dutra\n▪Fiona Havers\n▪Michael Whitaker\n▪John Su\n▪Karen Broder▪Eric Weintraub\n▪David Shay\n▪Anne Hause\n▪Pedro Moro\n▪Tom Shimabukuro\n▪Patricia Lloyd\n▪Richard Forshee\n▪Steven AndersonAcknowledgements\n30\nFor more information, contact CDC\n1-800 -CDC -INFO (232 -4636)\nTTY:  1 -888 -232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention.\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.", "summary": "Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. RSV Vaccination in Older Adults: Benefit -Risk Discussion Michael Melgar , MD Lauren Roper, MPH Advisory Committee on Immunization Practices February 29, 2024 There are…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-28-29-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-02-28-29/07-RSV-Adults-Melgar-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 31}
{"title": "08 RSV Adults Britton 508", "content": "Centers for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nRSV Vaccination in Older Adults:\nWork Group Interpretations\nAmadea Britton, MD\nAdvisory Committee on Immunization PracticesFebruary 29, 2024\n2This includes follow- up of the implementation and experience of the current shared \nclinical decision -making recommendation, understanding uptake of RSV vaccines \nacross age and demographic groups, consideration of new vaccine products , and \npotential expansion of RSV vaccines to younger age groups . \nHowever, the Work Group believes that contextualization and understanding of \ncurrent safety data are paramount in determining future preferred policy options \nfor the adult RSV vaccination program. \nTherefore, today’s Work Group interpretations focus primarily on the safety and benefit/risk data reviewed today. \nWe will then briefly review the proposed roadmap for expected future policy decisions. First, the Work Group would like to acknowledge that there are multiple \nconcurrent policy issues to consider in the older adult RSV vaccine \nlandscape. \n3Summarize Work Group interpretations of current RSV vaccine safety surveillance \ndata and the balance of estimated benefits vs potential risks associated with use of RSV vaccines in adults ages 60 years and older\nShare updated clinical considerations incorporating timing of RSV vaccine administration in shared clinical decision- making\nUpdate on plans for future policy considerations in the older adult RSV vaccine program Objectives\nWork Group interpretation of current RSV \nvaccine safety data and benefit/risk of RSV \nvaccination in adults ages 60 years and older\n5Due to the small number of cases, it was unclear whether the cases observed in the trials represented \na genuine association between RSV vaccination and risk of GBS or whether the cases observed in the \ntrials were due to chance alone. \nThe potential for increased risk of GBS was discussed extensively during deliberations for the older \nadult recommendation. ACIP concluded that the estimated benefits of RSV vaccination outweighed \npotential risks. \nHowever, ACIP recommended RSV vaccines be given using shared clinical decision- making with a \nhealthcare provider. The shared clinical decision- making recommendation was intended to \nfacilitate individualized risk -benefit discussions, acknowledging that the balance of risks and \nbenefits may depend on the characteristics of the individual vaccine recipient. \nClinical guidance advised that a patient’s risk for severe RSV -associated disease should be the core of \nshared clinical decision -making, with vaccination targeted to those who are at highest risk for severe \nRSV disease and therefore most likely to benefit from vaccination.The initial RSV vaccine recommendation for adults 60 years and older was made in \nthe setting of a small number of cases of inflammatory neurologic events (particularly GBS) observed in the clinical trials for both GSK and Pfizer’s RSV vaccines for older adults. \n6February May June NovemberDecember -\nJanuaryFebruaryRSV older adult vaccine safety surveillance timeline\nAbbreviations: ACIP = Advisory Committee on Immunization Practices, CISA = Clinical Immunization Safety Assessment Project, C MS = Centers for Medicare & Medicaid \nServices, FDA= Federal Drug Administration, GBS = Guillain -Barre syndrome, RSV = respiratory syncytial virus, VAERS = Vaccine Ad verse Event Reporting System, VRBPAC= \nVaccines and Related Biological Products Advisory Committee Meeting; VSD = Vaccine Safety Datalink\n*CISA is covered by a CDC Assurance of Confidentiality 2023 2024\nACIP votes to \nrecommend RSV vaccination for adults aged  ≥60 years , using \nshared clinical decision- making. Small number of GBS cases observed in the clinical trials in adults aged  ≥60 years for GSK \nand Pfizer RSV vaccines. Safety data shared at FDA VRBPAC \nand ACIP meetings.VAERS scientists \ncontinued monitoring and verifying GBS \nreports; CISA continued review.First preliminary safety surveillance data available from CDC V -\nsafe, CDC VSD and FDA \nCMS. Number of GBS cases in VAERS raised possibility \nthat cases observed might be above expected background rate. CDC \norganized CISA calls with \nclinical experts inneurology to \nreview cases of GBS \nreported to VAERS.*RSV vaccines licensed for use in adults aged ≥60 years. Information on trial GBS cases included in product package inserts. Safety  \nmonitoring commences immediately post -\nlicensure.\n7Today, CDC’s Immunization Safety Office and FDA shared \npreliminary data from multiple surveillance systems: VAERS, VSD, and the FDA -CMS partnership.\nThe data from these systems have been shared as near real -time \nfindings and allow us to be immediately responsive to early signals.\nTogether, the data support a potential increased risk for GBS after RSV vaccination among adults aged ≥60 years .\nHowever, due to uncertainty and limitations in these early data, there is currently insufficient evidence to confirm whether RSV \nvaccination is associated with increased risk for GBS in older \nadults, or to estimate the magnitude of any increase in GBS risk after RSV vaccination. \nAssessing the risk for GBS following receipt of the RSV vaccine among older adults in more robust analyses in active vaccine safety surveillance systems will be crucial and is underway. Surveillance with a focus on early detection of increased risk \nof GBS after RSV vaccination began immediately post -\nlicensure.\n+\n8Any increase in potential risk of GBS should be placed in the context of the \nbenefits of RSV vaccination. \nEarlier in this session, we summarized what we know about the estimated benefits of RSV vaccine and compared that to what we know currently about potential risk of GBS. This benefit- risk analysis showed that:\n–From a population perspective, the estimated benefits of RSV vaccination outweigh  the estimated \nrisks for adults 60 years and older. \n–Benefits of RSV vaccination vary by age group and RSV incidence.\n–Benefits likely also vary by individual -level risk  of severe RSV disease and by timing of vaccination \nrelative to the RSV season.\nWe also saw data demonstrating that adults with certain chronic conditions are at increased risk of severe RSV disease, even at younger ages. How do these new data impact the Work Group’s thinking about RSV \nvaccine for older adults? \n9The Work Group also reviewed examples from other licensed and recommended \nvaccines of benefit -risk considerations in practice.\nSeasonal influenza vaccine: routine annual influenza vaccination is recommended for all persons aged \n≥6 months who do not have contraindications. Adults aged ≥65 years  should preferentially receive high -\ndose, recombinant, or adjuvanted influenza vaccines.1\n–The data on the association between GBS and seasonal influenza vaccination are variable and \ninconsistent across influenza seasons. If there is an increased risk of GBS following influenza vaccination \nit is small, on the order of 1–2 additional cases per million doses of influenza vaccine administered.  \nStudies also suggest that it is more likely that a person will get GBS after getting the influenza disease \nthan after influenza vaccination.2\n1. Grohskopf LA, et al. Prevention and Control of Seasonal Influenza with Vaccines: Recommendations of the Advisory Committee on  Immunization Practices —  United States, 2023 –24 Influenza Season. \nMMWR Recomm  Rep 2023;72(No. RR -2):1 –25. http://dx.doi.org/10.15585/mmwr.rr7202a1  \n2. Vellozzi C, Iqbal S, and Broder K. Guillain -Barré Syndrome, Influenza, and Influenza Vaccination: The Epidemiologic Evidence, Clinical Infectious Diseases , Volume 58, Issue 8, 15 April 2014, Pages 1149 –\n1155, https://doi.org/10.1093/cid/ciu005 .9\n10Summary of RSV and Influenza disease -associated hospitalizations, estimated vaccine-\navertable disease hospitalizations, and potential vaccine -associated GBS risk\nDisease -associated \nhospitalizations per 1 million \npopulation per year in the U.S.Estimated disease -associated \nhospitalizations avertable per 1 \nmillion persons vaccinatedPotential vaccine -associated GBS \ncases per1 million persons vaccinated\nRSV1,700 – 2,800\n1\namong adults ages 65 and olderOver two RSV seasons, among adults ages 60 and olderGSK: 2,400 (1,800 – 3,700)\n2\nPfizer: 2,700 (2,100 – 4,200)2GSK: 10 (2 –18) cases3\nPfizer: 25 (7 –43) cases3\nNot adjusted for background rate of GBS\nExpected from background rate : \n5cases of GBS (95% CI: 4.8, \n5.4) per 1million doses given\n4\nInfluenza3,200 – 9,2005\namong adults ages 65 and olderOver one influenza season,\namong adults ages 65 and older\n2,000 (300 –  5,500)6Variable and inconsistent across \ninfluenza seasons. If there is an \nincreased risk, it is small: ~1–2 \nadditional  cases per million doses \ngiven7,8\n1. CDC RSV -NET data 2016– 2020, 2022 –2023 (unpublished)\n2. Unpublished benefit/risk analysis presented at this ACIP meeting (February 2024).\n3. FDA analysis of CMS data. Includes GBS cases in a 42 -day risk interval post -RSV -vaccination, adjusted for claims delay, among be neficiaries 65 and older with Parts A and B coverage who did not have a GBS claim in the 365 days before vaccination. These are rates of GBS identified by inpatient claims data and are decreased \nby 29% to account for the positive predictive value of diagnostic codes in identifying chart -confirmed GBS cases. A GBS backgrou nd rate is not subtracted from these rates.\n4. FDA analysis of CMS data. Background rate based on GBS cases observed per 100,000 person -years among Medicare beneficiaries 65 and older with Parts A and B coverage in 2022. Beneficiaries must not have had an International Classification of Diseases, 10 th revision, clinical modification (ICD -10-CM) diagnostic code \nfor GBS in the 365 days preceding January 1, 2022. Rate per 100,000 person -years applied used to estimate cases expected over 42 -day follow -up for 1 million persons.\n5. CDC Influenza Burden 2016– 2020, 2022 –2023: https://www.cdc.gov/flu/about/burden/past -seasons.html\n6. Ellen KD, Gebremariam  A, Rose A, et al. Cost -effectiveness of routine annual influenza vaccination by age and risk status. Vaccine: 41 (29): 4239- 424 8. 2023. https://doi.org/10.1016/j.vaccine.2023.04.069\n7. Vellozzi C, Iqbal S, and Broder K. Guillain -Barré Syndrome, Influenza, and Influenza Vaccination: The Epidemiologic Evidence, Clinical Infectious Diseases , Volume 58, Issue 8, 15 April 2014, Pages 1149 –1155, https://doi.org/10.1093/cid/ciu005 .\n8. Committee to Review Adverse Effects of Vaccines; Institute of Medicine; Stratton K, Ford A, Rusch  E, et al., editors. Adverse Effects of Vaccines: Evidence and Causality. Washington (DC): National Academies Press (US); 2011  Aug 25. 6, Influenza Vaccine. Available from: https://www.ncbi.nlm.nih.gov/books/NBK190013/\nInfluenza Vaccine - Adverse Effects of Vaccines - NCBI Bookshelf (nih.gov).10\n11The Work Group also considered examples from other licensed and recommended \nvaccines of benefit -risk consideration in practice.\n\n–\nRecombinant zoster vaccine: CDC recommends two doses of recombinant zoster vaccine (RZV, \nShingrix) 2 –6 months apart for adults aged ≥50 years and for adults aged ≥19 years who are or will be \nimmunocompromised, for prevention of herpes zoster (shingles) and related complications .3,4\n–3-6 additional cases of GBS projected per million RZV vaccinated .5\n–Risk- benefit analysis incorporated available data on risk of GBS following zoster disease and vaccination with RZV\n3. Dooling KL, et al. Recommendations of the Advisory Committee on Immunization Practices for Use of Herpes Zoster Vaccines. MMW R Morb  Mortal Wkly  Rep 2018;67:103 –108. http://dx.doi.org/10.15585/mmwr.mm6703a5  \n4. Anderson TC, et al. Use of Recombinant Zoster Vaccine in Immunocompromised Adults Aged ≥19 Years: Recommendations of the Advi sory Committee on Immunization Practices — United States, 2022. MMWR Morb  Mortal \nWkly  Rep 2022;71:80 –84. http://dx.doi.org/10.15585/mmwr.mm7103a2  \n5. Janusz CB, et al. Projected risks and health benefits of vaccination against herpes zoster and related complications in US ad ults. Hum Vaccin  Immunother. 2022 Nov 30;18(5):2060668. \nhttps://doi.org/10.1080/21645515.2022.206066811\n12Experience with recombinant zoster vaccine (Shingrix) \nIn 2019, a statistical safety signal for GBS following \nrecombinant zoster vaccine was identified in VSD; evidence was insufficient to confirm the initial signal.\nFDA, CDC, and collaborators conducted additional extensive safety assessments.\n1,2\nUsing data from this safety surveillance, a formal \nanalysis evaluating health risks and benefits was \nundertaken. Epidemiologic data suggesting a potentially elevated risk of GBS following an \nepisode of herpes zoster (HZ) in the U.S. adult \npopulation was also included.\n3\nIn this analysis , benefits were assumed to accrue \nover a period of 20 years after vaccination.\nVaccination averted 43,000– 63,000 cases of HZ, \nincluding GBS complications, per million \nvaccinated per 10-year age cohort compared to 3 –\n6 additional cases of GBS  projected per million \nvaccinated with recombinant zoster vaccine in the same population.\n4\nImportantly, RSV disease is not directly comparable to herpes zoster disease. \n* Projected number of averted cases of postherpetic neuralgia and ocular complications have been rounded to two significant f igures. For exact numbers see Janusz et al. below. \n1. Goud R, et al. Risk of Guillain -Barré Syndrome Following Recombinant Zoster Vaccine in Medicare Beneficiaries. JAMA Intern Med. 2021 Dec 1;181(12):1623 -1630. doi: 10.1001/jamainternmed.2021.6227.\n2. Nelson JC, et al. Active Postlicensure  Safety Surveillance for Recombinant Zoster Vaccine Using Electronic Health Record Data. Am J Epidemiol. 2023 Feb 1;192(2):205 -216. doi: 10.1093/ aje/kwac170.\n3. Anderson TC, et al. Risk of Guillain -Barré syndrome following herpes zoster, United States, 2010 -2018. Hum Vaccin  Immunother. 2021 Dec 2;17(12):5304 -5310. doi : 10.1080/21645515.2021.1985890.\n4. Janusz CB, et al. Projected risks and health benefits of vaccination against herpes zoster and related complications in US ad ults. Hum Vaccin  Immunother. 2022 Nov 30;18(5):2060668. https://doi.org/10.1080/21645515.2022.2060668Age group (years)Postherpetic neuralgiaOcular complicationsDeaths Incremental \nGBS increase Notes\n50-59 5,500 4,300 47\n3 – 6 • 20-year time horizon\n• Incremental GBS increase subtracts background rate of \nGBS and HZ -\nassociated GBS \naverted\n• Outcomes averted per million 1 -dose or \n2-dose series60-69 9,400 5,500 62\n70-79 12,000 5,700 171\n80-89 12,000 5,200 155\n90-99 11,000 3,900 116Projected cases* of postherpetic neuralgia, ocular complications, and \ndeath averted through recombinant  zoster vaccine per million vaccinated, \ncompared to incremental GBS increase per million412\n13Based on this review of currently available data, the Work Group \ncontinues to believe that the estimated benefits of RSV \nvaccination outweigh potential risks when vaccination is \nimplemented using the current recommendation: Adults aged \n≥60 years may receive RSV vaccination, using shared clinical decision-making.\n14However, the Work Group expressed that \nestimated benefits most clearly outweigh \npotential risks among adults 60 and older who are at increased risk of severe RSV disease. \nThis includes a dults who are 60 and older with \nchronic medical conditions such as chronic lung \ndiseases, heart failure, immune compromise, those of more advanced age, and those living in long -term care facilities (e.g., nursing homes).  A majority of Work Group members expressed that the balance of \nestimated benefits outweighed potential risks for all adults 60 and older.\n\n15Estimated age distribution of national RSV -associated hospitalizations, ICU admissions, and in-\nhospital deaths among adults ≥18 years, RSV -NET, 2022 –2023, compared with U.S. population\nUnpublished data. Underlying rates are adjusted using multipliers for the frequency of RSV testing during each season and for  the sensitivity of RSV diagnostic tests. Estimates \nfrom 2022- 2023 are preliminary. These estimates use the same multipliers as for 2019 -2020.\n*As of 2022. https://www.census.gov/popclock/  42.9%\n37.1%\n58.0%\n9.2%23.9%\n26.8%\n22.8%\n13.0%20.4%\n22.6%\n11.3%\n24.1%12.8%\n13.6%\n7.9%\n53.7%\n0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%Hospitalizations\nICU admissions\nIn-hospital deaths\nU.S. Adult Population*≥75 65-74 50-64 18-49\nU.S. Adult Population *Age group, years:\n16Underlying medical conditions* among non- pregnant adults ≥18 years with RSV -\nassociated hospitalizations — RSV -NET, 2014 –2015 to 2017 –2018 and 2022 –2023\nMajor underlying condition categories Unweighted \nN=7,479Weighted \n%\nCardovascular disease (overall) 5,141 57.4\nObesity 2,798 39.0\nDiabetes 2,484 34.1\nCOPD 2,248 31.4\nHeart failure 1,984 28.0\nChronic kidney disease 2,003 27.0\nAsthma 1,789 24.0\nCoronary artery disease (includes CABG, MI) 1,718 24.0\nNeurologic condition 1,628 22.6\nImmune compromised 1,567 20.8\nChronic metabolic disease, not including diabetes 1,417 19.3\nOther chronic lung disease 995 17.1\nChronic liver disease 538 7.2\nAutoimmune/inflammatory disease 310 4.5\nBlood disorders 287 4.194.3% of adults ≥18 \nyears with RSV -\nassociated hospitalization \nhad at \nleast one underlying medical condition\n:\n•31.4%: 1– 2 conditions\n•62.9%: ≥3 conditions\n*Clinical data, including underlying medical conditions, were collected for all patients with laboratory -confirmed RSV hospitalizations during the 2014 –2015 to 2017– 2018 seasons, and for an \nage- and site -stratified random sample of patients with laboratory -confirmed RSV hospitalizations during the 2022 –2023 season. Data are presented as unweighted case counts and weighted \npercentages that were weighted for the probability of selection.\n17For these adults, the benefit from RSV vaccination may be \nlower. \nHowever, the Work Group felt that  these adults might still \nbenefit from vaccination depending on their individual situation and the decision to get vaccinated should be based \non discussion with a healthcare provider .\nThe shared clinical decision- making recommendation \ncontinues to support this flexibility. The Work Group noted that for older adults who do not have any chronic \nmedical conditions  and who do not live in long -term care facilities , the risk \nof severe RSV disease is lower. \n18Providers will need support in appropriately framing shared clinical \ndecision -making discussions with their older adult patients.\nProviders may need additional communications materials clarifying which of their patients aged ≥60 years are at increased risk of severe RSV \ndisease and would benefit most from vaccination.\nProviders may need more materials to support discussing current safety \ndata. The Work Group also stresses that discussion of benefits vs \npotential risks should remain the core of shared clinical decision -\nmaking. \n19Uncertainty in estimates of risk \n–Estimated risk is uncertain and confidence intervals are wide\n–Among adults electing to receive RSV vaccine, background rates of GBS are uncertain\n•Adults receiving RSV vaccine may differ from those who do not choose vaccines in underlying health status or \nother ways that could impact background risk of GBS\n•It is unclear if recipients of different RSV vaccine products may also differ in ways that could affect their underlying risk of GBS independent of RSV vaccination\nUncertainty in estimates of benefit\n–Although estimated benefits are based on the best available data, we do not yet have estimates of \nreal -world vaccine effectiveness against RSV -associated hospitalization and death\n–The extent to which effectiveness will extend to older adults at highest risk of severe RSV disease \n(those aged ≥75 years, those who are frail, those with immune compromise) is also unknown\nThere may be other important sources of uncertainty \n–What do we need to understand about coadministration of RSV vaccine with other recommended \nvaccines? \n–Is RSV disease itself associated with a risk of GBS? The Work Group acknowledges the challenge of multiple sources of \nuncertainty. \n20V-safe data monitoring ongoing \nVAERS data monitoring ongoing with CISA experts reviewing selected reports \nVaccine Safety Datalink \n–Rapid cycle analysis (RCA) will be performed as soon as sufficient data (plan for first RCA March 2024)\n–Power may be limited, especially for Pfizer RSV vaccine\nFDA -CMS partnership ongoing\n–Plan for self-controlled case series as soon as sufficient follow -up time accrued\nBoth manufacturers (Pfizer and GSK) conducting post -marketing studies\n–GSK: Sentinel system self-controlled risk interval active surveillance, final report 2031\n–Pfizer: CMS claims data active surveillance, final report 2030\nWill conduct more robust risk- benefit analysis once active surveillance analyses are \nable to characterize risk and estimates of real- world vaccine effectiveness are \navailableSafety surveillance is ongoing and new data will be shared as soon as they \nbecome available. The preliminary data shared today are the first in what \nwill be a series of rigorous analyses across multiple different platforms.  \nAbbreviations: CISA = Clinical Immunization Safety Assessment Project, CMS = Centers for Medicare & Medicaid Services, FDA= F ederal Drug Administration, VAERS = Vaccine \nAdverse Event Reporting System\n21In the interim, the Work Group wishes to affirm the importance of the RSV \nvaccination program. RSV is a disease that causes significant morbidity \nand mortality among persons across the age spectrum.\nThe Work Group is cognizant that premature changes in the RSV \nvaccination program have the potential to limit access to RSV vaccine. \nCDC and the Work Group are committed to incorporating what we are learning from post -licensure data in a transparent way that ensures \nsafety for the public and clarity for providers.CDC and the Adult RSV Work Group will be engaged in ongoing assessment. Future older adult RSV policy will be responsive to what is learned over the coming months.\nWork Group considerations on timing of \nRSV vaccination for adults ages 60 years and older\n231.RSV seasonality had been disrupted by the COVID -19 pandemic. Based on the two \npreceding RSV seasons (2021 -2022 and 2022 -2023), it was not clear when RSV \ncirculation might start, peak, and decline . Therefore, it was also unclear when to \ntime RSV vaccination to optimize benefit to an individual. In June 2023, the decision to recommend year -round RSV \nvaccination was based on 3 considerations: \n24National weekly* RSV percent positivity of PCR results, \nNREVSS July 2016 –June 2023\n*All results presented from nucleic acid amplification tests which represent >90% of the diagnostic tests reported to NREVSS.  \nThe last three weeks of data may be less complete. NREVSS is an abbreviation for the National Respiratory and Enteric Virus Surv eillance System. \nFor more information on NREVSS, please visit www.cdc.gov/surveillance/nrevss . \nRSV: Respiratory Syncytial Virus. Types A and B are reported but not shown separately in this report.\nResults are crude, and therefore may differ from smoothed results reported online. 2016- 20, \npre-COVID -19\n2020- 212021- 222022- 23\n02468101214161820\n2728293031323334353637383940414243444546474849505152123456789101112131415161718192021222324252627\nJul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun JulPercent Positive\nMonth and MMWR Week\n251.\n2.Clinical trial data indicated that both GSK and Pfizer RSV vaccines offered protection \nfor at least two RSV seasons. Therefore, regardless of when someone received a dose of RSV vaccine it would be expected to protect the recipient at least through the upcoming RSV season. In June 2023, the decision not to specify seasonal \nadministration of RSV vaccine was based on 3 considerations: \n261.\n2.\n3.There were limited data available to understand if (or when) revaccination would be \nbeneficial. Not having a seasonal end to administration offered maximum flexibility and opportunity for people to receive protection for the next season. In June 2023, the decision not to specify seasonal \nadministration of RSV vaccine was based on 3 considerations: \n27National weekly* RSV percent positivity of PCR results, \nNREVSS July 2016 –February 2024\n*All results presented from nucleic acid amplification tests which represent >90% of the diagnostic tests reported to NREVSS.  \nThe last three weeks of data may be less complete. NREVSS is an abbreviation for the National Respiratory and Enteric Virus Surv eillance System. \nFor more information on NREVSS, please visit www.cdc.gov/surveillance/nrevss . \nRSV: Respiratory Syncytial Virus. Types A and B are reported but not shown separately in this report.\nResults are crude, and therefore may differ from smoothed results reported online. 2016- 20, \npre-COVID -19\n2020- 212021- 222022- 23\n2023- 24\n02468101214161820\n2728293031323334353637383940414243444546474849505152123456789101112131415161718192021222324252627\nJul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun JulPercent Positive\nMonth and MMWR Week\n28Predictable  RSV seasonality makes it possible to anticipate the likely RSV season onset, peak, \nand offset.\nMaximizing benefits is also desirable as we continue ongoing safety monitoring.The Work Group concludes it is now advisable for providers and patients \nto consider timing of RSV vaccination as part of shared clinical decision -\nmaking  discussions.\nFor most older adults, benefits will be highest when RSV \nvaccination is given in the late summer or early fall, just before \nthe onset of RSV season , so that vaccine recipients experience \nhighest protection during the times of peak RSV transmission over the fall and winter.\nBecause clinical trial data suggests that protection will wane over \ntime, vaccinating just before a season starts also maximizes \nprotection for subsequent seasons for which the vaccine offers \nprotection.\n29For adults ages 60 years and older who remain unvaccinated and \nwho decide with their healthcare provider to get RSV vaccination, \nthe best time for vaccination is just before the start of the next \nRSV season to maximize the benefits of the vaccine.\nNOT  a transition to a formal seasonal recommendation for RSV \nvaccination. \n–Older adults may continue to receive RSV vaccination year -round , using \nshared clinical decision -making. \n–Intent is to allow providers and patients maximum flexibility. Patients with \ninfrequent healthcare contact may benefit from every opportunity to vaccinate.\nNOT  a recommendation for annual re -vaccination.\n–RSV vaccine for adults 60 and older is currently still recommended as a one -time \nvaccine. What does it mean to include timing of vaccination in shared \nclinical decision -making? \nIn most of the \nUnited States, \nRSV vaccination \nwill have the most \nbenefit if given in \nlate summer or \nearly fall.\n30Mean weekly RSV percent positivity of PCR results by census region, \nNREVSS*, 2015 –2019\n*Data from Florida, Hawaii, and Alaska are excluded. \nAll results presented from nucleic acid amplification tests which represent >90% of the diagnostic tests reported to NREVSS.NREVSS is an abbreviation for the National Respiratory and Enteric Virus Surveillance System. For more information on NREVSS, please visit www.cdc.gov/surveillance/nrevss\n. \nRSV: Respiratory Syncytial Virus. Types A and B are reported but not shown separately in this report.\nResults are crude, and therefore may differ from smoothed results reported online. Northeast\nMidwestSouth\nWest\n0%5%10%15%20%25%Percent Positive\nWeek ending date\n31Mean weekly RSV percent positivity of PCR results by census region, \nNREVSS*, 2015 –2019\n*Data from Florida, Hawaii, and Alaska are excluded. \nAll results presented from nucleic acid amplification tests which represent >90% of the diagnostic tests reported to NREVSS.NREVSS is an abbreviation for the National Respiratory and Enteric Virus Surveillance System. For more information on NREVSS, please visit www.cdc.gov/surveillance/nrevss\n. \nRSV: Respiratory Syncytial Virus. Types A and B are reported but not shown separately in this report.Results are crude, and therefore may differ from smoothed results reported online. Northeast\nMidwestSouth\nWest\n0%5%10%15%20%25%\nJul-7\nJul-21\nAug-4\nAug-18\nSep-1\nSep-15\nSep-29\nOct-13\nOct-27\nNov-10Nov-24\nDec-8\nDec-22\nJan-5\nJan-19\nFeb-2\nFeb-16\nMar-2\nMar-16Mar-30\nApr-13Apr-27\nMay-11\nMay-25\nJun-8\nJun-22Percent Positive\nWeek ending dateRSV season onset varies by \nregion, from September to \nNovember  in most of the \nUnited States.\n32Mean weekly RSV percent positivity of PCR results by census region, \nNREVSS*, 2015 –2019\n*Data from Florida, Hawaii, and Alaska are excluded. \nAll results presented from nucleic acid amplification tests which represent >90% of the diagnostic tests reported to NREVSS.NREVSS is an abbreviation for the National Respiratory and Enteric Virus Surveillance System. For more information on NREVSS, please visit www.cdc.gov/surveillance/nrevss\n. \nRSV: Respiratory Syncytial Virus. Types A and B are reported but not shown separately in this report.Results are crude, and therefore may differ from smoothed results reported online. Northeast\nMidwestSouth\nWest\n0%5%10%15%20%25%\nJul-7\nJul-21\nAug-4\nAug-18\nSep-1\nSep-15\nSep-29\nOct-13\nOct-27\nNov-10Nov-24\nDec-8\nDec-22\nJan-5\nJan-19\nFeb-2\nFeb-16\nMar-2\nMar-16Mar-30\nApr-13Apr-27\nMay-11\nMay-25\nJun-8\nJun-22Percent Positive\nWeek ending dateVaccination just prior to the \nRSV season means from August to October  in most of \nthe United States.\n33Weekly and Cumulative Projected RSV Vaccinations Administered in Retail Pharmacies by \nProduct, Adults 60 years and older, August 12, 2024 – February 2, 2024. Data Source: IQVIA*\n*IQVIA Custom Weekly LRx; File \ndelivery date 2/8/24 .The weekly number of \nRSV vaccine doses \nadministered appears \nto have peaked and \nnow be declining. \nOther upcoming policy considerations for RSV \nvaccination in adults ages 60 years and older  \n35Additional policy issues Adult RSV Work Group plans \nto address in June 2024\n1.Potential FDA approval of Moderna mRNA- 1345 vaccine for use in \nadults aged ≥60 years\n2.Potential FDA approval of GSK RSV vaccine for use in adults aged 50 –\n59 years “at increased risk for RSV disease” ( regulatory decision expected \nJune 2024 )\n3.Consideration of whether shared clinical decision -making remains the \npreferred policy option.35\n36The Work Group notes that safety and efficacy were demonstrated in their phase 3 \nsafety & efficacy trial, most notably: \noInterim efficacy analysis with median 9 months follow -up per participant\nVE against RSV LRTI with ≥2 symptoms: 63.3% (95% CI 48.7 –73.7%)\nVE against RSV LRTI with ≥3 symptoms: 63.0% (95% CI 37.3 –78.2%)\nTwo recorded RSV -associated hospitalizations, both in the placebo arm. Unable to estimate efficacy against \nhospitalization.\nNo recorded RSV -associated deaths, including in the placebo arm.\noNo reported cases of GBS, ADEM, or other inflammatory neurologic events in clinical trials of mRNA -1345 (N=18,245 \nvaccine recipients in their pivotal Phase II/III trial).\noNo reported cases of confirmed myocarditis or pericarditis among recipients of mRNA -1345 within 42 days after \nvaccination.\nIf licensed by FDA for use in adults 60 and older, Work Group plans to present full GRADE/ EtR to support ACIP deliberations around adding Moderna mRNA -1345 as an \noption for adults 60 and older to protect against lower respiratory tract disease. Work Group interpretations of initial phase 3 safety and \nefficacy of Moderna’s mRNA -1345 RSV vaccine\nAbbreviations: VE = Vaccine effectiveness, LRTI=Lower respiratory tract infection, GBS=Guillain -Barré Syndrome, ADEM=Acute disse minated \nencephalomyelitis\n37In October 2023, GSK presented data to ACIP demonstrating that the humoral immune \nresponse to a single dose of GSK RSV vaccine in adults 50 –59 years is non -inferior to that in \nadults 60 and older .\nThe Work Group noted that if FDA licensure is granted for use of GSK’s RSV vaccine in adults aged 50– 59 years at increased risk of RSV disease, then ACIP will likely need to make a policy \nrecommendation on:\n–Whether RSV vaccination should be recommended in this age group?\n–And if so, how will CDC define populations at increased risk of RSV disease?\nToday we saw data demonstrating the relative risk of severe RSV disease across a range of chronic medical conditions by age group. \nWork Group members broadly agree that use of RSV vaccine among adults with certain chronic medical conditions aged 50 –59 years is likely to have public health benefit, however, \nupcoming data on safety and effectiveness will be pivotal to determine the preferred policy option in this age group. Work Group interpretations of GSK RSV vaccine for use in \nadults 50 –59 at increased risk of RSV disease\n38Lastly, the Work Group has begun analyzing the experience with shared clinical \ndecision -making this season.  \nFeedback from many partners that shared clinical decision- making has been \nchallenging to implement. \nFor the time being, the Work Group continues to endorse shared clinical decision-making as we learn more about the estimated benefits and potential risks associated with the currently available RSV vaccines. \nHowever, the Work Group has begun reviewing evidence to discuss changing the current recommendation for adults ≥60 from shared clinical decision- making to:\n–A universal  recommendation among adults older than a specific age cut -off AND\n–A risk-based  recommendation in adults 50 years and older up to that age cut -off Work Group interpretations on whether shared clinical \ndecision -making will remain the preferred policy option  \n39The Work Group is considering a shift away from shared \nclinical decision -making for multiple reasons.\nA universal recommendation among adults over a specific age cut -off may be easier \nto message and implement.\nA risk -based recommendation among adults 50 and older, but below the universal \nage cut -off may be easier to implement (persons at risk would be more concretely \ndefined) and ensure persons being vaccinated have highest potential to benefit.\nAnticipate presenting additional data on these topics at the June 2024 ACIP meeting\nThe Work Group emphasizes that future preferred policy options will be contingent \non incoming data, including safety analyses and vaccine effectiveness. \n40CDC and the Adult RSV Work \nGroup will continue to \ntransparently share new \ninformation with ACIP and \nthe public and incorporate it \ninto future policy \nrecommendations to ensure \nthe greatest benefit and least \nrisk in the RSV vaccine \nprogram for older adults. The first -ever respiratory virus season in which there were vaccines available to protect \nolder adults against RSV disease is coming to a close . \nThis is a new vaccine program and remains an evolving landscape with the potential for \nnew products and expansion of current products into new age groups.\nData from this season is still incoming. Over the coming months CDC and the Work Group will be analyzing these data to inform discussion of future RSV vaccine policy for \nolder adults.\nData from pre -licensure clinical trials and early findings from post- licensure vaccine \nsafety surveillance suggests the potential for increased risk of GBS after RSV vaccination in older adults; however, these early data are insufficient to confirm if there is an \nincreased risk.\nAssessing the risk for GBS following receipt of the RSV vaccine among older adults in more robust analyses in active vaccine safety surveillance systems will be crucial and is \nunderway.\nCurrently, the Work Group continues to endorse the benefits of RSV vaccination for \nadults 60 and older, especially those at increased risk of severe RSV disease, using shared \nclinical decision -making.\nBenefits can be maximized by administering RSV vaccine just before the start of RSV \nseason and the Work Group recommends that timing of RSV vaccination should be a part of the shared clinical decision -making discussion. Summary \nFor more information, contact CDC\n1-800- CDC- INFO (232 -4636)\nTTY:  1 -888 -232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention.\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.", "summary": "Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. RSV Vaccination in Older Adults: Work Group Interpretations Amadea Britton, MD Advisory Committee on Immunization PracticesFebruary 29, 2024 2This includes follow- up of…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-28-29-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-02-28-29/08-RSV-Adults-Britton-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 41}
{"title": "01 Meningitis Loehr 508", "content": "Introduction to Meningococcal Vaccines Session\nJamie Loehr, MD\nACIP Meningococcal Work Group Chair\nFebruary 29, 2024National Center for Immunization & Respiratory Diseases\nThe findings and conclusions in this presentation are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention.\n▪Revisiting the adolescent meningococcal vaccine \nschedule\n–Does ACIP concur with the 4 options for further assessment?\n–What additional information will help ACIP determine the preferred \noption?\n▪GSK’s MenABCWY  vaccineTwo Terms of Reference\n2 of 6\nUpcoming ACIP Meetings\n▪February 2024\n•Terms of reference\n–Adolescent schedule change\n–GSK’s MenABCWY  vaccine\n▪June 2024\n•U.S. epidemiology\n–Disease burden stratified by race/ethnicity in adolescents\n–Cases/deaths averted by MenACWY  dose at 11 -12 years \n–Risk factors for serogroup B disease among college students\n–Breakthrough disease in vaccinated individuals\n•WG considerations\n3 of 6\nUpcoming ACIP Meetings, cont.\n▪October 2024\n•GRADE/ EtR\n•Cost -effectiveness analysis\n▪February 2025\n•Vote\n4 of 6\nEvidence to be Reviewed by the Work Group\n▪Epidemiology of meningococcal disease\n▪Expected public health impact\n▪Immunogenicity and safety*\n▪GRADE and EtR\n▪Cost -effectiveness\n*GSK Pentavalent vaccine only5 of 6\nMeningococcal Vaccines Work Group Members\nACIP Members on the WG\n•Jamie Loehr (Chair)\n•Wilbur Chen\nEx Officio WG Members\n•Margaret Bash (FDA)\n•Mark Connelly (FDA)\n•Francisco Leyva (NIH)\nWG Liaisons and Consultants\n•Katherine Poehling (Wake Forest)\n•Lynn Bahta (MN DOH)\n•Amra Resic  (AAFP)\n•Samir Shah (AAP) \n•Barbara Fluty (ACHA)\n•Karyn Lyons (AIM)\n•Paul Cieslak (CSTE)\n•Kathy Hsu (IDSA)\n•Joseline Zafack (NACI)\n•Jeff Goad (NFID)\n•Jessica Cataldi (PIDS)\n•Amy Middleman (SAHM)\n•David Stephens (Emory) CDC Contributors\n•Sarah Schillie (DBD/NCIRD)\n•Jennifer Collins (DBD/NCIRD)\n•Lucy McNamara (DBD/NCIRD)\n•Xiaoyu Dong (ISD/NCIRD)\n•Ismael Ortega -Sanchez (CORVD/NCIRD)\n•Andrew Leidner (ISD/NCIRD)\n•LeAnne Fox (DBD/NCIRD)\n•Susan Hariri (DBD/NCIRD)\n•Amy Rubis (DBD/NCIRD)\n•Noele Nelson (DBD/NCIRD)\n•Alison Albert (DBD/NCIRD)\n•Angela Jiles (DBD/NCIRD)\n•Jonathan Duffy (DHQP/NCEZID)\n•Tanya Myers (DHQP/NCEZID) \n•Liz Velazquez (ISD/NCIRD)\n•Jessica MacNeil (ACIP Secretariat)\n•Melinda Wharton (ACIP Secretariat) \nGRADE/ EtR Support\n•Doug Campos -Outcalt (Arizona)\n•Rebecca Morgan (Case Western Reserve)6 of 6", "summary": "Introduction to Meningococcal Vaccines Session Jamie Loehr, MD ACIP Meningococcal Work Group Chair February 29, 2024National Center for Immunization & Respiratory Diseases The findings and conclusions in this presentation are those of the authors and do not necessarily represent the official  position of the Centers for Disease Control and Prevention. ▪Revisiting the adolescent meningococcal vaccine  schedule –Does ACIP concur with the 4 options for further assessment? –What additional…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-28-29-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-02-28-29/01-Meningitis-Loehr-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 6}
{"title": "02 Meningitis Schillie 508", "content": "Revising the Adolescent Meningococcal Vaccine Schedule:  \nTerm of Reference and Considerations \nSarah Schillie, MD, MPH, MBA\nFebruary 29, 2024National Center for Immunization & Respiratory Diseases\nThe findings and conclusions in this presentation are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention.\n▪Vaccine recommendations and coverage\n▪Epidemiology\n▪Duration of vaccine -induced protection\n▪Options for changing the immunization scheduleOutline\n2 of 24\n*Both (all) doses must be from same manufacturerAdolescent Meningococcal Vaccine Recommendations\n▪MenACWY :  \n•Dose #1:  11 –12 years\n•Dose #2:  16 years\n▪MenB * (shared clinical decision -making)\n•2- or 3-dose series between 16 –23 years of age (preferred range:  16 –18 years)\n▪MenABCWY :\n•Recommended when both MenACWY  and MenB  indicated at same visit \n3 of 24\n▪MenACWY\n–≥1 dose at 13 years:  84.5% (81.3% -87.2%)*\n–≥1 dose at 16 years:  89.8% (87.4% -91.8%)\n–≥2 doses at 17 years:  60.8% (57.5% -63.9%)**\n▪MenB\n–≥1 dose at 17 years:  29.4% (26.5% -32.4%)\n–≥2 doses at 17 years:  11.9% (10.0% -14.1%)2022 Meningococcal Vaccine Coverage\n*Coverage varies by metropolitan statistical area, poverty status, race/ethnicity, and health insurance status, although conf idence \nintervals largely overlap\n**Does not include adolescents who received 1st dose of MenACWY  vaccine at age ≥16 years\nPingali C, et al. MMWR Morb  Mortal Wkly  Rep 2023:  http://dx.doi.org/10.15585/mmwr.mm7234a34 of 24\nMeningococcal Disease Incidence ― United States, 1996 -2022*\nx\n5 of 24\n*2021 -2022 NNDSS data are preliminary\nAverage Annual Meningococcal Disease Incidence by \nAge-Group and Serogroup ― United States, 2020 -2022*\n6 of 24\nAverage Annual Meningococcal Disease Incidence by \nAge-Group and Serogroup ― United States, 2012 -2021*\n7 of 24\n▪Preliminary data indicate 416* cases in 2023 \n–Highest number of cases since 2014\n▪Rates of disease greatest in children <1 year of age\n▪Second peak in adolescence; among cases in 2021:\n–19 of 210 (9.0%) total cases in 11 -23 year -oldsIncreasing Case Counts\n*Confirmed and probable cases8 of 24\n▪Among adolescents 11 -15 years old, incidence decreased:\n–16.3% (12.1% -20.3%) during prevaccine  period\n–27.8% (20.6% -34.4%) during post -primary dose period\n▪Among adolescents 16 -22 years old, incidence decreased:\n–10.6% (6.8% -14.3%) during post -primary dose period\n–35.6% (29.3% -41.0%) during post -booster dose period\n▪Estimated 222 cases of serogroup C,W,Y disease averted \nthrough vaccination of adolescents from 2006 -2017Cases Averted Due to Vaccination\nMbaeyi S, et al. JAMA Pediatr  2020  9 of 24\nIncidence of Meningococcal Disease by Serogroups Following \nMenACWY  Vaccine Implementation\nSource: National Notifiable Diseases Surveillance System (NNDSS) data with additional serogroup data from Active Bacterial Co re surveillance (ABCs) and state health departments ACWY disease incidence substantially \ndecreased  in adolescentsB disease incidence was similar  in \nadolescents over time\n00.050.10.150.20.250.3\n11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26Incidence per 100,000\nAgeSerogroups A, C, W, Y\n2006-2010 2015-201900.050.10.150.20.25\n11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26Incidence per 100,000\nAgeSerogroup B\n2006-2010 2015-2019 10 of 24\n▪College students have a 3.5 -fold (95% CI: 2.2 -5.4) higher risk of serogroup B \ndisease than non -college students\n▪Serogroup B incidence peaks for 19 year -old college students and declines \nafter age 20\nSerogroup B Disease Risk is Higher among \nCollege Students\nMbaeyi S, et al.  Pediatr  2019  11 of 24\nAdditional Factors Associated with \nIncreased Risk among College Students\n▪4-year college students had a 5.2-fold (95% CI: 3.6 -7.7) higher risk of serogroup B \ndisease than non -undergraduates aged 18 -24 years\n–Risk among 2 -year college students was comparable to non -undergraduates (RR 1.0, \n95% CI: 0.4 -2.1)\n▪First -year students were at 3.8-fold (95% CI: 2.4 -6.0) higher risk of serogroup B \ndisease than non -first-year students\n▪On-campus residents at  2.9-fold (95% CI: 1.8 -4.6) higher risk of serogroup B \ndisease than off -campus residents\n▪Students participating in Greek life were at 9.8-fold (95% CI: 4.6 -21.2) higher risk \nof serogroup B disease than other students during outbreaks\nWeil L, et al. OFID 2023  12 of 24\n▪MenACWY\n–Protection wanes 3 to <8 years postvaccination \n•<1 year:  79%\n•1 to <3 years:  69%\n•3 to <8 years:  61%\n▪MenB\n–Protection wanes 1 -2 years following primary vaccinationDuration of Vaccine -Induced Protection\nMbaeyi S, et al. MMWR Recomm  Rep 2020  https://www.cdc.gov/mmwr/volumes/69/rr/pdfs/rr6909a1 -H.pdf ; Stephens D, et al. \nin Plotkin’s Vaccines 8th edit 2024; Dretler  A, et al. Hum Vacc & Immuno  2018; Cohn A, et al. Pediatr  2018\n13 of 24\n▪Bexsero is recommended for prevention of serogroup B \nmeningococcal disease\n–Some protection against gonorrhea is also likely  \n▪N. meningitidis and N. gonorrhoeae closely genetically \nrelated \n– ~80 to 90% sequence homology\n▪Potential for outer membrane vesicle (OMV) -containing \nMenB  vaccines (e.g., Bexsero) to provide protection against \nN. gonorrhoeae\nPetousis -Harris H, et al. Lancet 2017;  Wang B, et al. Lancet 2022; Abara W, et al. Lancet 2022;  Bruxvoort  K, et al. CID 2023Effectiveness of Bexsero against Gonorrhea\n14 of 24\n▪Revisions to the schedule should optimize protection \nagainst meningitis\n▪Considerations for meningitis protection include: \n–Ages at higher risk for meningitis\n–Recent meningitis epidemiology\n–Duration of vaccine -induced protection\n15 of 24Revising the \nAdolescent Meningococcal Vaccine Schedule\n▪Maintaining harmonization with existing adolescent \nvaccination platform\n▪Pentavalent vaccine provides opportunity to reduce \nnumber of injections\n16 of 24Revising the \nAdolescent Meningococcal Vaccine Schedule, cont.\n▪MenACWY  \n–Possibly eliminate 11 -12 year -old dose\n–Change recommended age given recent epidemiology \n▪MenB\n–Change recommended age to increase protection upon college entry  \n–Routine or risk -based recommendation\n•If risk -based recommendation, include permissive language for vaccination of persons \nin age group requesting protection but who may lack risk factors such as college \nattendance (equity considerations)  Options for Revising \nAdolescent Meningococcal Vaccine Schedule\n17 of 24\nSchedule Options for Further Consideration\nOptionACWY \nDose#1ACWY \nDose#2B Dose#1 B Dose#2\nCurrent \nrecomm .11–12 yrs 16 yrs16 yrs – 23 years (preferred 16 –18 yrs) \nSCDM\n1 11–12 yrs 16 yrs 16 yrs 17–18 yrs\n2 11–12 yrs 16 yrs 16 yrs risk-based 17–18 yrs risk-based\n3 No dose 16 yrs 16 yrs risk -based 17–18 yrs risk-based\n4 15 yrs 17–18 yrs 17–18 yrs 17–18 yrs\nProposed recommendations are for routine vaccination unless specified as \n“risk -based”; option numbers do not represent ordering of preference\nSCDM, shared clinical decision -making 18 of 24\nSchedule Options for Further Consideration, etc.\nOptionACWY \nDose#1ACWY \nDose#2B Dose#1 B Dose#2\nCurrent \nrecomm .11–12 yrs 16 yrs16 yrs – 23 years (preferred 16 –18 yrs) \nSCDM\n1 11–12 yrs 16 yrs 16 yrs 17–18 yrs\n2 11–12 yrs 16 yrs 16 yrs risk-based 17–18 yrs risk-based\n3 No dose 16 yrs 16 yrs risk -based 17–18 yrs risk-based\n4 15 yrs 17–18 yrs 17–18 yrs 17–18 yrs\nProposed recommendations are for routine vaccination unless specified as \n“risk -based”; option numbers do not represent ordering of preference\nSCDM, shared clinical decision -making 19 of 24\nSchedule Options for Further Consideration, etc.\nOptionACWY \nDose#1ACWY \nDose#2B Dose#1 B Dose#2\nCurrent \nrecomm .11–12 yrs 16 yrs16 yrs – 23 years (preferred 16 –18 yrs) \nSCDM\n1 11–12 yrs 16 yrs 16 yrs 17–18 yrs\n2 11–12 yrs 16 yrs 16 yrs risk-based 17–18 yrs risk-based\n3 No dose 16 yrs 16 yrs risk -based 17–18 yrs risk-based\n4 15 yrs 17–18 yrs 17–18 yrs 17–18 yrs\nProposed recommendations are for routine vaccination unless specified as \n“risk -based”; option numbers do not represent ordering of preference\nSCDM, shared clinical decision -making20 of 24\n▪Variability in desire to keep vs. eliminate 11 –12 year -old dose of \nMenACWY\n–Favor keeping:  Has taken years to ingrain the 11 –12 year -old platform, 11 –12 \nyear -old dose may have reduced carriage and ‘worked’ \n–Favor eliminating:  Epi seems to support starting series at 16 years\n▪Consider administering MenB  dose #1 at age 15 years* \n▪Try to achieve acceptable efficacy for duration of disease incidence peak in \nyoung adulthoodSynthesis of Work Group Comments\n*Not among 4 options for consideration 21 of 24\n▪Oppose SCDM recommendations\n–Poor uptake, missed opportunities, implementation challenges, lack of strong \nrecommendation prevents many institutions from implementing policies, not \nunderstandable to clinicians  \n–Interest in changing MenB  to risk -based or routine recommendation\n▪Harmonization of MenACWY  and MenB  schedules may reduce number of \ninjections \n–Extra antigen administration (as may occur with administration of pentavalent \nvaccine) has not been a concern before\n▪Change in schedule may impact school requirements Synthesis of Work Group Comments, cont.\n22 of 24\n▪Does ACIP concur with the 4 schedule \noptions for further assessment?\n▪What additional information will help ACIP \ndetermine the preferred option?Discussion\n23 of 24\nAcknowledgements\n▪Lucy McNamara\n▪Jennifer Collins\n▪Samuel Crowe\n▪Sancta St. Cyr\n24 of 24", "summary": "Revising the Adolescent Meningococcal Vaccine Schedule:   Term of Reference and Considerations  Sarah Schillie, MD, MPH, MBA February 29, 2024National Center for Immunization & Respiratory Diseases The findings and conclusions in this presentation are those of the authors and do not necessarily represent the official  position of the Centers for Disease Control and Prevention. ▪Vaccine recommendations and coverage ▪Epidemiology ▪Duration of vaccine -induced protection ▪Options for changing the…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-28-29-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-02-28-29/02-Meningitis-Schillie-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 24}
{"title": "03 Meningitis Schillie 508", "content": "GSK Pentavalent MenABCWY  Vaccine:  Term of Reference  \nSarah Schillie, MD, MPH, MBA\nFebruary 29, 2024National Center for Immunization & Respiratory Diseases\nThe findings and conclusions in this presentation are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention.\n▪Two new MenABCWY  vaccines:\n–Pfizer (“ Penbraya ,” ACIP voted October 2023)\n–GSK (clinical trials)\n▪Each vaccine is a combination of an existing:\n–MenACWY  vaccine   and  \n–MenB  vaccine\n▪Each vaccine assessed separately by Work Group\n–Lack of data directly comparing Pfizer and GSK Pentavalent vaccinesPentavalent MenABCWY  Vaccines\n2 of 10\nPfizer ( Penbraya ) GSK*\nACWY \ncomponentNimenrix  (not licensed in U.S.) Menveo\nB component Trumenba Bexsero\nSchedule 2 doses, 6 months apart 2 doses, 6 months apart*\nAge 10-25 years 10-25 years*\nClinical trial \nparticipantsStudied in MenACWY  primed \nand naive subjects; all MenB  \nnaiveStudied in MenACWY  primed \nand naive subjects; MenB  \nnaïve in phase 3 trials\nFuture studiesLonger interval studies \nunderwayLonger interval studies \nunderway\nGonorrhea \nprotectionNo Yes/some\n*Vaccine not yet licensed in U.S. and this slide represents anticipated schedule and age indications Pfizer’s and GSK’s MenABCWY  Vaccines\n3 of 10\nPolicy Questions for GSK’s Pentavalent Vaccine\n▪Should the pentavalent vaccine be included as an option for MenACWY /MenB  \nvaccination in people currently recommended to receive both vaccines at the \nsame visit?\n– For example, 16 year olds*\n▪Should the pentavalent vaccine be included as an option for people currently \nrecommended to receive MenACWY  only?\n–For example, 11 –12 year olds\n▪Should the pentavalent vaccine be included as an option for people currently \nrecommended to receive MenB  only?\n– For example, during a serogroup B outbreak\n*16 year olds who decide to receive the MenB  vaccine based on shared clinical decision making4 of 10\nOutcomes Table\nOutcome Importance* To be Included in Evidence Profile\nMeningococcal disease caused by \nserogroups A, B, C, W, and YCritical Yes\nPersistent immunity Important Yes\nShort -term immunity Critical Yes\nInterference with other \nrecommended vaccines \nadministered concurrentlyImportant Yes\nSerious adverse events Critical Yes\nNon -serious adverse events Important Yes\nGonorrhea prevention Important Yes\n* Three options: critical, important but not critical, of limited importance for decision making. 5 of 10\nPICO policy question #1 (of 3) — Should the GSK pentavalent vaccine be included as an \noption for MenACWY/ MenB  vaccination in people currently recommended to receive  \nboth vaccines at the same visit?\nPopulation All individuals aged 10 years or older currently recommended to receive \nMenACWY and MenB  vaccines at the same visit\nIntervention Vaccination with GSK’s pentavalent vaccine\nComparison Vaccination with a currently licensed MenACWY vaccine and a MenB vaccine\nOutcomes •Meningococcal disease caused by serogroups A, B, C, W, and Y\n•Short -term immunity\n•Persistent immunity\n•Interference with other recommended vaccines administered concurrently\n•Serious adverse events\n•Non -serious adverse events\n•Gonorrhea prevention6 of 10\nPICO policy question #2 (of 3) — Should the GSK pentavalent vaccine be included \nas an option for people currently recommended to receive  MenACWY only ?\nPopulation All individuals aged 10 years or older currently recommended to receive \nMenACWY  vaccine only\nIntervention Vaccination with GSK’s pentavalent vaccine\nComparison Vaccination with a currently licensed MenACWY vaccine\nOutcomes •Meningococcal disease caused by serogroups A, C, W, and Y\n•Short -term immunity\n•Persistent immunity\n•Interference with other recommended vaccines administered concurrently\n•Serious adverse events\n•Non -serious adverse events\n•Gonorrhea prevention 7 of 10\nPICO policy question #3 (of 3) — Should the GSK pentavalent vaccine be included \nas an option for people currently recommended to receive MenB only ?\nPopulation All individuals aged 10 years or older currently recommended to receive MenB  \nvaccine only\nIntervention Vaccination with GSK’s pentavalent vaccine\nComparison Vaccination with a currently licensed MenB  vaccine\nOutcomes •Meningococcal disease caused by serogroup B\n•Short -term immunity\n•Persistent immunity\n•Interference with other recommended vaccines administered concurrently\n•Serious adverse events\n•Non -serious adverse events\n•Gonorrhea prevention 8 of 10\nDiscussion\n9 of 10\nAcknowledgements\n▪Lucy McNamara\n▪Jennifer Collins\n▪Samuel Crowe\n▪Sancta St. Cyr▪CDC Division of STD \nPrevention\n10 of 10", "summary": "GSK Pentavalent MenABCWY  Vaccine:  Term of Reference   Sarah Schillie, MD, MPH, MBA February 29, 2024National Center for Immunization & Respiratory Diseases The findings and conclusions in this presentation are those of the authors and do not necessarily represent the official  position of the Centers for Disease Control and Prevention. ▪Two new MenABCWY  vaccines: –Pfizer (“ Penbraya ,” ACIP voted October 2023) –GSK (clinical trials) ▪Each vaccine is a combination of an existing: –MenACWY …", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-28-29-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-02-28-29/03-Meningitis-Schillie-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 10}
{"title": "01 Pneumococcal Loehr 508", "content": "Centers for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nPneumococcal Vaccines\nFebruary 2024, ACIP Meeting\nFebruary 29, 2024\nPneumococcal Vaccine Work Group ChairJames Loehr, MD, FAAFP\nACIP Members\nJamie Loehr  (Chair, acting)\nSarah Long \nEx Officio Members\nJeffrey Kelman  (CMS)\nLucia Lee            (FDA)\nTina Mongeau   (FDA)\nUzo  Chukwuma (IHS)\nMamodikoe Makhene (NIH, primary)\nMeenu Upadhyay (NIH, alternate)\nLiaison Representatives\nLynn Fisher                (AAFP)\nJames Campbell      (AAP/COID)\nJason Goldman         (ACP)\nDavid Nace                 (AGS/ AMDA)\nCora Hoover               (AIM, primary)Risa Claytor                 (HRSA)\nJames McAuley         (IDSA)\nEva Wong                 (NACI)\nRobert Hopkins    (NFID, primary)\nWilliam Schaffner     (NFID, alternate)\nVirginia Caine            (NMA)\nConsultants\nMonica Farley            (VAMC/Emory)\nKeith Klugman          (BMGF)\nKathy Poehling         (Wake Forest)\nArthur Reingold        (UC Berkley)\nLorry Rubin                 (CCMC)\nRichard Zimmerman (U. of Pittsburgh)Pneumococcal Vaccines Work Group\nDivision of Bacterial Diseases\nDiepreye Ayabina \nAdam Cohen\nRyan Gierke             \nJennifer Farrar     \nNoele Nelson    \nImmunization Safety Office\nPedro Moro               \nImmunization Services Division\nJanelle King\nAndrew Leidner\nLiz VelazquezArctic Investigations Program\nMarc Fischer\nCDC Lead\nMiwako Kobayashi\nGRADE/ EtR  consultants\nDoug Campos -Outcalt\nRebecca MorganCDC Contributors and Consultants\nInvasive pneumococcal disease incidence reached a historically low level \nearly in the COVID -19 pandemic but is returning toward pre -COVID \nlevels\nIPD=invasive pneumococcal disease; 2022 data in gray are preliminary\nABCs Bact  Facts Interactive Data Dashboard | CDC\n\nAround the same time, pneumococcal conjugate vaccines PCV15 \nand PCV20  were recommended for both adults and children\n2021 2023 2022\nPCV15:  ChildrenPCV20:  Expanded \nindication for adults \nwho previously received PCV13\nPCV20:  ChildrenPCV15 and PCV20:  \nAdults who have not received PCV or whose vaccination history is unknown\nAdditional Pneumococcal Vaccines in Advanced Stages of Development\n1 3 4 5 6\nA6B7 F9V1418C19A19F23F22F33F8 1\n0\nA11\nA1\n2F15B2 9N17F2015A15C16F23A23B24F3135B\nPCV15\nPCV20PPSV23\nPn-\nMAPS24v20\nB\nVAX -2420B\nV11620\nA\n1. Chichili  et al. Vaccine 2022; GSK Pipeline assets and clinical trials appendix Q4 2023  2. Wassil et al. Lancet ID 2023, ClinicalTrials.gov ID: NCT05297578, and NCT05844423; 3. FDA Grants Priority Review to Merck’s \nNew Biologics License Application for V116, an Investigational, 21- valent Pneumococcal Conjugate Vaccine Specifically Designed t o Protect Adults -  Merck.com . 24-valent pneumococcal vaccines:\n•Pn-MAPS24v (GSK): Completed phase 1/2 study for adults; Breakthrough  Therapy Designation \ngranted and Phase 3 study in preparation; undergoing phase 2 studies in infants1\n•VAX -24 (Vaxcyte ): Completed phase 1/2 studies for adults, undergoing phase 2 studies in infants2\n21-valent pneumococcal conjugate vaccine (V116, Merck):\n• BLA accepted by the FDA for priority review3\n25-valent  pneumococcal vaccine candidate (IVT PCV -25, Iventprise )\n•Completed Phase 2 dose ranging  study in young adults1\n31-valent  pneumococcal conjugate vaccine candidate (VAX- 31, Vaxcyte )\n•Completed enrollment of Phase 1/2 study in adults aged ≥50 years2Additional Pneumococcal Vaccines Under Development\n1. Inventprise  Completes Vaccination of Participants in a Phase 2 Dose Ranging Study of its 25 Valent Pneumococcal Vaccine Candidate –  Inventprise\n2. Vaxcyte  Completes Enrollment of Phase 1/2 Study Evaluating VAX- 31 for the Prevention of Invasive Pneumococcal Disease (IPD) in Adults Aged 50 and Older - Vaxcyte , Inc.\nThe following groups are currently recommended to receive a dose of \npneumococcal conjugate vaccine (PCV):\n•Adults aged ≥65 years who have not received a PCV1\n•Adults aged 19 –64 years with certain underlying conditions or risk factors2 who have \nnot received a PCV1\n•Certain adults who have received PCV13 but have not received PCV203 Current Pneumococcal Vaccine Recommendations for Adults \nand Vaccine Coverage \n1. Excludes PCV7\n2. alcoholism; chronic heart, liver, or lung disease; chronic renal failure; cigarette smoking; cochlear implant; congenital or acquired asplenia; CSF leak; diabetes mellitus; generalized malignancy; HIV infection; \nHodgkin disease; immunodeficiency; iatrogenic immunosuppression; leukemia, lymphoma, or multiple myeloma; nephrotic syndrome;  solid organ transplant; or sickle cell disease or other \nhemoglobinopathies\n3. Adults who have not completed the recommended vaccine series, or shared clinical decision -making for adults aged ≥65 years who h ave completed the recommended vaccine series\nPneumococcal Vaccine for Adults Aged ≥19 Years: Recommendations of the Advisory Committee on Immunization Practices, United S tates, 2023 | MMWR (cdc.gov)\nCoverage of ≥1 dose of any pneumococcal vaccine\n•Adults aged 19 –64 years with risk- based indication: 22.2%\n•Adults aged ≥65 years: 65.8%Adults with risk -based vaccine recommendations have lower \nvaccine coverage compared with those with age -based \nrecommendations\nVaccination Coverage among Adults in the United States, National Health Interview Survey, 2021 | CDC\n1. Should PCV21 be recommended for U.S. adults aged ≥19 years who \ncurrently have a recommendation to receive a PCV*?\n*Includes,\n• Adults aged ≥65 years who have never received a PCV\n• U.S. adults aged 19– 64 years with a risk condition, who have never received a PCV\n• U.S. adults aged ≥19 year who have received a PCV (i.e., PCV7, PCV13, or PCV15), but have not completed the recommended series\n2. Should PCV21 be recommended for U.S. adults aged 50 –64 years who \ncurrently do not have a risk -based pneumococcal vaccine indication?\n3. Should PCV21 be recommended for U.S. adults aged 19– 49 years who \ncurrently do not have a risk -based pneumococcal vaccine indication?\n•Questions 2 and 3 would result in a new age -based recommendation for these groups.Policy Questions Being Considered by the Work Group \nConsidering:\nAdditional pneumococcal vaccines for adults are currently under investigation and \nmay be approved in the near future, and  \nDynamic changes in pneumococcal disease incidence are anticipated post -COVID -19 \nand with increased uptake in PCV15/PCV20 in children and adults\n \n1. Do you have any feedback on the policy questions being considered by the WG?2. What additional data would be helpful to inform the discussions on PCV21 use in \nadults? Questions for the Committee\nIntroduction Dr. Jamie Loehr (ACIP , WG Chair)\nCurrent epidemiology of invasive pneumococcal \ndisease among adults in the United StatesMr. Ryan Gierke (CDC, NCIRD)\nInterim results from the Pneumococcal pNeumonia  Epidemiology, Urine serotyping, and \nMental Outcomes (PNEUMO) US studyDr. Wesley Self (Vanderbilt University Medical Center)\nPhase 3 clinical trial data of PCV21 Dr. Heather Platt\nPost -licensure PCV20 safety dataDr. Pedro Moro (CDC/NCEZID)Dr. Richard Forshee  (FDA)\nPreliminary WG interpretations of EtR and Next \nStepsDr. Miwako Kobayashi (CDC, NCIRD)Today’s Session", "summary": "Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. Pneumococcal Vaccines February 2024, ACIP Meeting February 29, 2024 Pneumococcal Vaccine Work Group ChairJames Loehr, MD, FAAFP ACIP Members Jamie Loehr  (Chair, acting)…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-28-29-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-02-28-29/01-Pneumococcal-Loehr-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 12}
{"title": "02 Pneumococcal Gierke 508", "content": "Centers for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nCurrent Epidemiology of Pneumococcal Disease \namong Adults, United States\nFebruary 2024, ACIP Meeting\nFebruary 29, 2024\nRyan Gierke, MPH\nOutline\nBackground on pneumococcal disease\nPneumococcal vaccine coverage in adults\nPneumonia incidence estimates in adults\nInvasive pneumococcal disease (IPD)\n–Impact of COVID- 19\n–Incidence by vaccine type\n–Serotype distribution\n2\nBogaert, Lancet Infect Dis 2004;4:144 -54Pneumococcal carriage is precursor to pneumococcal disease \nMore frequent\nLess frequent\n3\nBogaert, Lancet Infect Dis 2004;4:144 -54Noninvasive Disease\nInvasive DiseasePneumococcal carriage is precursor to pneumococcal disease \nMore frequent\nLess frequent\n4\nPCV20 coverage: 12% \n–Ranged from 9% (adults aged ≥85 years) to 25%  (adults aged 65 years)\n PCV15 coverage: 0.2%\n–Less than 1% across all agesPCV15 and PCV20 coverage among Medicare Part A/B \nbeneficiaries aged ≥65 years1, Oct 1, 2021 − Dec  31, 2023\n1.Based on age at the end of 2022\nUnpublished data courtesy of CDC ISD. Based on CMS data from January 17, 2024. \nEstimated proportion of adults who ever received any pneumococcal \nvaccination, National Health Interview Survey, 2021\nAge group % (95% CI)\nOverall (≥65 years) 65.8 (64.4 -67.2)\nOverall (19 –64years with risk -based indication ) 22.2 (21.0 -23.5)\nWhite 23.3 (21.7 -24.9)\nBlack 22.6 (19.2 -26.4)\nHispanic 19.0 (15.9 -22.6)*\nAsian 16.9 (12.0 -23.2)*\nOther 22.7 (16.3 -30.7)\n*p<0.05 for comparisons with white as the referencehttps://www.cdc.gov/vaccines/imz -managers/coverage/adultvaxview/pubs -\nresources/vaccination -coverage- adults -2021.html#summary\nEstimated incidence of pneumococcal disease in adults \naged ≥65 years\nDisease Estimated incidence \n(per 100,000 population)\nAll-cause hospitalized pneumonia1847–3,365 \nHospitalized noninvasive pneumococcal \npneumonia2105\nInvasive pneumococcal disease (IPD)3 24\n1. McLaughlin et al. Vaccine 2020 (limited to studies that collected data during or after 2010) \n2. Gierke et al. IDweek 2020. CDC’s Surveillance for NonInvasive  Pneumococcal Pneumonia ( SNiPP ), 2017  \n3. CDC ABCs, 2018 –2019 Case fatality ratio from IPD: 14%3\nKobayashi October 2022 ACIP meeting presentation 7\nIPD Incidence and Serotype Distribution Among \nAdults in the United States\n8\nMethods\nActive Bacterial Core surveillance (ABCs): \nActive laboratory and population- ba sed \nsurveillance, 10 sites\nPneumococcus  is olation from sterile site\nIsolates serotyped by whole -ge nome sequencing, Quellung, or PCR at reference \nlabs and grouped for analysis by vaccine type\nUS Census Bureau race -b ridged post -census population estimates used as \ndenominators\nOverall and serotype -s pecific IPD incidence rates (cases per 100,000 population)\nhttps://www.cdc.gov/abcs/methodology/surv-pop.html9\nIPD incidence rates, by age group, 2007 − 2022\n051015202530354045\n2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022Cases per 100,000 population\nYearAge <5 Age 19-49\nAge 50-64 Age ≥65\n10\n051015202530354045\n2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022Cases per 100,000 population\nYearAge <5 Age 19-49\nAge 50-64 Age ≥65IPD incidence rates, by age group, 2007 − 2022\nPCV13: children\n11\n051015202530354045\n2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022Cases per 100,000 population\nYearAge <5 Age 19-49\nAge 50-64 Age ≥65IPD incidence rates, by age group, 2007 − 2022\nPCV13: adultsPCV13: children\n12\n051015202530354045\n2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022Cases per 100,000 population\nYearAge <5 Age 19-49\nAge 50-64 Age ≥65IPD incidence rates, by age group, 2007 − 2022\nPCV13: adultsPCV13: children\n13COVID -19\n051015202530354045\n2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022Cases per 100,000 population\nYearAge <5 Age 19-49\nAge 50-64 Age ≥65IPD incidence rates, by age group, 2007 − 2022\nPCV15 & PCV20: \nadultsPCV13: adultsPCV13: children\nPCV15:  children\n14COVID -19\nProportion of adult IPD cases, with a risk -based indication, \n2018 − 2021\nAmong adult IPD cases, 82% – 87% had at least one risk -based \nindication for pneumococcal vaccination \n–Age 19- 49 years: 82%\n–Age 50 -64 years: 87% \n–Age ≥65 years: 87%\n15\nSerotypes contained in current and new pneumococcal vaccines\n1 3 4 5 6\nA6B7 F9V1418C19A19F23F22F33F8 1\n0\nA1\n1\nA1\n2\nF1\n5\nB2 9\nN17\nF2015\nA1\n5C16F23A23B24F3135B\nPCV15\nPCV20PPSV23PCV21\n16\nSerotypes contained in PCV20 and PCV21\n1 3 4 5 6\nA6B7 F9V1418C19A19F23F22F33F8 1\n0\nA1\n1\nA1\n2\nF1\n5\nB2 9\nN17\nF2015\nA1\n5C16F23A23B24F3135B\nPCV20\nPCV21\n17\n1 3 4 5 6\nA6B7 F9V1418C19A19F23F22F33F8 1\n0\nA1\n1\nA1\n2\nF1\n5\nB2 9\nN17\nF2015\nA1\n5C16F23A23B24F3135B\nPCV20\nPCV21\nFor analysis purposes:\n•PCV20 non- PCV21: includes serotypes 1, 4, 5, 6B, 9V, 14, 18C, 19F, 23F, 15B\n18Serotypes contained in PCV20 and PCV21\n1 3 4 5 6\nA6B7 F9V1418C19A19F23F22F33F8 1\n0A1\n1\nA1\n2\nF1\n5\nB2 9\nN17\nF2\n015\nA1\n5C16F23A23B24F3135B\nPCV20\nPCV21\nFor analysis purposes:\n•PCV20 non- PCV21: includes serotypes 1, 4, 5, 6B, 9V, 14, 18C, 19F, 23F, 15B\n•PCV20 and PCV21: includes serotypes 3, 6A, 7F, 19A, 22F, 33F, 8, 10A, 11A, 12F, +6C \n19Serotypes contained in PCV20 and PCV21\n1 3 4 5 6\nA6B7 F9V1418C19A19F23F22F33F8 1\n0\nA1\n1\nA1\n2\nF1\n5\nB2 9\nN17\nF2015\nA1\n5C16F23A23B24F3135B\nPCV20\nPCV21\nFor analysis purposes:\n•PCV20 non- PCV21: includes serotypes 1, 4, 5, 6B, 9V, 14, 18C, 19F, 23F, 15B\n•PCV20 and PCV21: includes serotypes 3, 6A, 7F, 19A, 22F, 33F, 8, 10A, 11A, 12F, +6C \n•PCV21 non- PCV20:  includes serotypes 9N, 17F, 20, 15A, 15C, 16F, 23A, 23B, 24F, 31, 35B\n20Serotypes contained in PCV20 and PCV21\nIPD incidence rates among adults 19 -64 years old, by vaccine type,  \n2011 – 2022\nPCV15 & PCV20: adults19-49 years old 50-64 years old\n02468101214161820\n2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022*Cases per 100,000 population\nYearsPCV20/ non-PCV21 PCV20 and PCV21\nPCV21/non-PCV20 Non-Vaccine Type\nPCV20/ non- PCV21 serotype:  1, 4, 5, 6B, 9V, 14, 18C, 19F, 23F, 15B\nPCV20/ in -PCV21 serotypes: 3, 6A, 7F, 19A, 22F, 33F, 8, 10A, 11A, 12F, +6C \nPCV21/ non -PCV20  serotypes: 9N, 17F ,20, 15A, 15C, 16F, 23A, 23B, 24F, 31, 35B 02468101214161820\n2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022*Cases per 100,000 population\nYearsPCV20/ non-PCV21 PCV20 and PCV21\nPCV21/non-PCV20 Non-Vaccine Type\n*2022 estimates are not finalized\n21COVID -19COVID -19\n02468101214161820\n2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022*Cases per 100,000 population\nYearsPCV20/ non-PCV21 PCV20 and PCV21\nPCV21/non-PCV20 Non-Vaccine Type\n02468101214161820\n2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022*Cases per 100,000 population\nYearsPCV20/ non-PCV21 PCV20 and PCV21\nPCV21/non-PCV20 Non-Vaccine TypeIPD incidence rates among adults 19 -64 years old, by vaccine type,  \n2011 – 2022\n19-49 years old 50-64 years old\nPCV20/ non- PCV21 serotype:  1, 4, 5, 6B, 9V, 14, 18C, 19F, 23F, 15B\nPCV20/ in -PCV21 serotypes: 3, 6A, 7F, 19A, 22F, 33F, 8, 10A, 11A, 12F, +6C \nPCV21/ non -PCV20  serotypes: 9N, 17F ,20, 15A, 15C, 16F, 23A, 23B, 24F, 31, 35B *2022 estimates are not finalized\n22COVID -19\nCOVID -19\n0510152025303540\n2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022Cases per 100,000 population\nYearsPCV20/ non-PCV21 PCV20 and PCV21 PCV21/ non-PCV20 Non-Vaccine TypeIPD incidence rates among adults ≥65 years old, by vaccine type, \n2011 – 2022\nPCV15 & PCV20: \nadultsPCV13: adults ≥65\nPCV20/ non- PCV21 serotype:  1, 4, 5, 6B, 9V, 14, 18C, 19F, 23F, 15B\nPCV20/ in -PCV21 serotypes: 3, 6A, 7F, 19A, 22F, 33F, 8, 10A, 11A, 12F, +6C \nPCV21/ non -PCV20  serotypes: 9N, 17F ,20, 15A, 15C, 16F, 23A, 23B, 24F, 31, 35B *\n*2022 estimates are not finalized\n23COVID -19\n1345366\n0102030405060708090100Percent IPD\nPCV20/ non-PCV21 PCV20 and PCV21\nPCV21/ non-PCV20 NVT747388\n0102030405060708090100Percent IPD\nPCV20/ non-PCV21 PCV20 and PCV21\nPCV21/ non-PCV20 NVTProportion of IPD by vaccine -type among adults with a pneumococcal \nvaccine indication, 2018 − 2022\nPCV20/ non- PCV21 serotype:  1, 4, 5, 6B, 9V, 14, 18C, 19F, 23F, 15B\nPCV20/ in -PCV21 serotypes: 3, 6A, 7F, 19A, 22F, 33F, 8, 10A, 11A, 12F, +6C \nPCV21/ non -PCV20  serotypes: 9N, 17F ,20, 15A, 15C, 16F, 23A, 23B, 24F, 31, 35B PCV21:\n85%  coverage\n24PCV20:\n54%  coveragePCV21:81%  coverage\nPCV20:\n58%  coverage19-64 years old (with a risk -based indication) ≥65 years old\nConclusion\nDuring the COVID- 19 pandemic, rates of IPD declined but are now returning \nto pre -pandemic levels\n>80% of adult IPD cases have a risk -based indication for vaccination\nPCV21 has greater coverage of the serotypes causing IPD in adults compared \nto PCV20\n–PCV20 covers 54–58% of adult IPD\n–PCV21 covers 81–84% of adult IPD\n25\nFor more information, contact CDC\n1-800- CDC- INFO (232 -4636)\nTTY:  1 -888 -232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention.\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nQuestions\nSupplemental slides\n27\nSerotypes contained in current and new pneumococcal vaccines\n1 3 4 5 6\nA6B7 F9V1418C19A19F23F22F33F8 1\n0\nA1\n1\nA1\n2\nF1\n5\nB2 9\nN17\nF2015\nA1\n5C16F23A23B24F3135B\nPCV15\nPCV20PPSV23PCV21\nFor analysis purposes:\n•PCV15+6C  includes serotype 6C with PCV15 types due to cross protection from 6A \nantigen \n28\nSerotypes contained in current and new pneumococcal vaccines\n1 3 4 5 6\nA6B7 F9V1418C19A19F23F22F33F8 1\n0\nA1\n1\nA1\n2\nF1\n5\nB2 9\nN17\nF2015\nA1\n5C16F23A23B24F3135B\nPCV15\nPCV20PPSV23PCV21\n29For analysis purposes:\n•PCV15+6C  includes serotype 6C with PCV15 types due to cross protection from 6A \nantigen\n•PCV20/ non- PCV15: includes serotypes  8, 10A, 11A, 12F, and 15B\n1 3 4 5 6\nA6B7 F9V1418C19A19F23F22F33F8 1\n0\nA1\n1\nA1\n2\nF1\n5\nB2 9\nN17\nF2015\nA1\n5C16F23A23B24F3135B\nPCV15\nPCV20PPSV23PCV21\nFor analysis purposes:\n•PCV15+6C includes serotype 6C with PCV15 types due to cross protection from 6A \nantigen \n•PCV20/ non- PCV15: includes serotypes 8, 10A, 11A, 12F, and 15B\n•PPSV23/ non- PCV20:  includes serotypes  2, 9N, 17F, and 20 \n30Serotypes contained in current and new pneumococcal vaccines\n1 3 4 5 6\nA6B7 F9V1418C19A19F23F22F33F8 1\n0\nA1\n1\nA1\n2\nF1\n5\nB2 9\nN17\nF2015\nA1\n5C16F23A23B24F3135B\nPCV15\nPCV20PPSV23PCV21\nFor analysis purposes:\n•PCV15+6C includes serotype 6C with PCV15 types due to cross protection from 6A \nantigen \n•PCV20 non- PCV15: includes serotypes 8, 10A, 11A, 12F, and 15B\n•PPSV23 non- PCV20:  includes serotypes  2, 9N, 17F, and 20 \n•PCV21 non- PPSV23:  includes serotypes 15A, 15C, 16F, 23A, 23B, 24F, 31, 35B\n31Serotypes contained in current and new pneumococcal vaccines\n02468101214161820\n2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022Cases per 100,000 persons\nYearPCV15+6C PCV20/ non-PCV15 PPSV23/ non-PCV20\nPCV21/non-PPSV23 Non-Vaccine TypeIPD incidence rates among adults 19 -64 years old, by vaccine type,  \n2011 – 2022\nPCV20 non- PCV15 serotypes: 8, 10A, 11A, 12F, 15B\nPPSV23 non -PCV20 serotypes: 2, 9N, 17F, 20\nPCV21 non- PPSV23 serotypes: 15A, 15C, 16F, 23A, 23B, 24F, 31, 35 19-49 years old 50-64 years old\n02468101214161820\n2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022*Cases per 100,000 persons\nYearPCV15+6C PCV20/ non-PCV15 PPSV23/ non-PCV20\nPCV21/non-PPSV23 Non-Vaccine Type\n*2022 estimates are not finalized*\n32\n0510152025303540\n2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022*Cases per 100,000 persons\nYearPCV15+6C PCV20/ non-PCV15 PPSV23/ non-PCV20 PCV21/non-PPSV23 Non-Vaccine TypeIPD incidence rates among adults ≥65 years old, by vaccine type, \n2011 – 2022\nPCV15 & PCV20: \nadults\nPCV20 non- PCV15 serotypes: 8, 10A, 11A, 12F, 15B\nPPSV23 non -PCV20 serotypes: 2, 9N, 17F, 20\nPCV21 non- PPSV23 serotypes: 15A, 15C, 16F, 23A, 23B, 24F, 31, 35 PCV13: adults ≥65\n*2022 estimates are not finalized\n33\n1345366\n0102030405060708090100Percent IPD\nPCV20/ non-PCV21 PCV20 and PCV21\nPCV21/ non-PCV20 NVT421615216\n0102030405060708090100Percent IPD\nPCV15+6C PCV20/non-PCV15\nPPSV23/non-PCV20 PCV21/non-PPSV23\nNVTProportion of IPD by vaccine -type among adults aged 19 -64 years, with a \nrisk-based indication, 2018 -2022\nPCV20/ non- PCV15 serotypes: 8, 10A, 11A, 12F, 15B\nPPSV23/ non -PCV20 serotypes: 9N, 17F ,20\nPCV21/ non- PPSV23 serotypes: 15A, 15C, 16F, 23A, 23B, 24F, 31, 35 81% \ncoverage\n58% coverage \nPCV20/ non- PCV21 serotype:  1, 4, 5, 6B, 9V, 14, 18C, 19F, 23F, 15B\nPCV20/ in -PCV21 serotypes: 3, 6A, 7F, 19A, 22F, 33F, 8, 10A, 11A, 12F, +6C \nPCV21/ non -PCV20  serotypes: 9N, 17F ,20, 15A, 15C, 16F, 23A, 23B, 24F, 31, 35 34\n747388\n0102030405060708090100Percent IPD\nPCV20/ non-PCV21 PCV20 and PCV21 PCV21/ non-PCV20 NVT42129298\n0102030405060708090100Percent IPD\nPCV15+6C PCV20/ non-PCV15 PPSV23/ non-PCV20\nPCV21/ non-PPSV23 NVTProportion of IPD by vaccine -type among adults age ≥65 years, \n2018 -2022\nPCV20/ non- PCV15 serotypes: 8, 10A, 11A, 12F, 15B\nPPSV23/ non -PCV20 serotypes: 2, 9N, 17F ,20\nPCV21/ non- PPSV23 serotypes: 15A, 15C, 16F, 23A, 23B, 24F, 31, 35 PCV20/ non- PCV21 serotype:  1, 4, 5, 6B, 9V, 14, 18C, 19F, 23F, 15B\nPCV20/ in -PCV21 serotypes: 3, 6A, 7F, 19A, 22F, 33F, 8, 10A, 11A, 12F, +6C \nPCV21/ non -PCV20  serotypes: 9N, 17F ,20, 15A, 15C, 16F, 23A, 23B, 24F, 31, 35 PCV21:\n85%  coverage\nPCV20:54%  coverage\n35", "summary": "Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. Current Epidemiology of Pneumococcal Disease  among Adults, United States February 2024, ACIP Meeting February 29, 2024 Ryan Gierke, MPH Outline Background on…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-28-29-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-02-28-29/02-Pneumococcal-Gierke-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 35}
{"title": "03 Pneumococcal Self 508", "content": "Public\nInterim Results from the PNEUMO Study\n. \nPneumococcal pNeumonia Epidemiology, Urine serotyping, and \nMental Outcomes study\nFebruary 29, 2024\nStudy Leadership\nWesley H. Self, MD\nVanderbilt UniversityJ. Jackson Resser , MS\nVanderbilt UniversityKelly D. Johnson, PhDMerck & Co., Inc.\n1 Funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USANadine Rouphael , MD\nEmory University\nPublic\nPNEUMO study overview\n•Adults 18+ years hospitalized with \ncommunity acquired pneumonia (CAP)Target \nPopulation\n•Multi -country, prospective, population -\nbased active surveillance studyDesign\n•Estimate pneumococcal pneumonia \nincidence and serotype prevalence (using \nMerck PCV15 and V116 SSUADs), with \nlongitudinal evaluation of functional status, quality of life and costObjectives►Incidence hospitalized pneumococcal CAP\n►Incidence hospitalized PCV15-  and\nV116 - type pneumococcal CAP\n►Direct medical cost\n►Work loss\n►Functional status \n►Cognitive status \n►Quality of Life (EQ -5D)Up to 6 \nmonths \npost -\ndischarge\n2\nPublic\nPneumonia surveillance  with prospective, real -time enrollment of \nadults hospitalized with CAP (including HCAP)\nHCAP, healthcare associated pneumonia US PNEUMO sites: enrollment Sept 2018 - present\nNashville, Tennessee\n(2 hospitals) Atlanta, Georgia\n3\nPublicEligibility criteria\nInclusion  Criteria\n1.Age ≥ 18 years  old\n2.Hospitalized\n3.Clinical signs and/or  symptoms of an acute  respiratory  illness (e.g., new  shortness of breath,  cough)\n4.Clinical signs and/or  symptoms of an acute  infection (e.g., fever,  leukocytosis)\n5.Radiologic  evidence  of pneumonia  interpreted  by a radiologist  (x-ray or CT) \nExclusion  Criteria\n1.Prior enrollment  in this study  within  the past  30 days  (to avoid  multiple  enrollments for same  episode  of \npneumonia).\n2.Development  of pneumonia  >72 hours  after  hospital admission  \n3.Inability  to obtain  consent  within  72 hours  of hospital admission  \n4.Inability  or unwillingness of the patient  to provide  a urine  sample  within  72 hours  of hospital admission .\n5.Non -pneumonia  illness completely  explains the patient’s  acute  symptoms.  4\nPublic\nTests for S. pneumoniae\n•Urine collection from patients at enrollment\n    (1) BinaxNow pneumococcal urinary antigen test (local testing by research team)\n   \n (2) Serotype- specific urinary antigen detection (SSUAD) assays:\n•Developed and performed by Merck laboratory\n•30 serotypes: \n•1, 3, 4, 5, 6A*, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15A, 15C#, 16F, 17F, 18C, 19A, 19F, 20A, 22F, \n23A, 23B, 23F, 24F, 31, 33F, 35B \n•All serotypes in PCV15, PCV20, and V116 included except 15B\n•Results of clinically -obtained bacterial cultures:\n•Sterile sites: blood, pleural fluid, BAL fluid, CSF, synovial fluid\n•Non -sterile sites: high-quality respiratory samples (>25 WBC, <10 epi) \n•sputum, endotracheal aspirate\n5* assay for serotype 6A has cross- reactivity with serotype 6C\n# assay for serotype 15C has mild cross- reactivity with serotype 15B\nPublic\nHospitalized adults screened for \neligibility\n(n = 5,385)\nEnrolled: adults hospitalized with \ncommunity acquired pneumonia (CAP)\n(n = 3,278)\nAnalyzed\n[All-cause CAP population]\n(n = 2,917)\nS. pneumoniae detected\n[Pneumococcal CAP population]\n(n = 352)S. pneumoniae not  detected\n[Non -pneumococcal CAP]\n(n = 2,565)\nS. pneumoniae culture positive \nfrom normally sterile site\n[Invasive pneumococcal CAP] \n(n = 51)S. pneumoniae detected outside \nnormally sterile site only\n[Non -invasive pneumococcal CAP] \n(n = 301)Not enrolled (n =2,107)\nEnrolled, not analyzed (n = 361)\n•No radiographic evidence of pneumonia (n=235)\n•Urine not tested by SSUAD (n = 114)  \n•Patient withdrew (n = 12)Enrolled Patients\n12.1%\npneumococcal\nprevalence\n85.5%\nof pneumococcal pneumonia\nwas non- invasive\nPublicPatient Characteristics: Demographics\nCharacteristic Pneumonia with \nS. pneumoniae detected \n(n= 352)Pneumonia without \nS. pneumoniae detected\n(n= 2565)P-value\nAge in years, median (IQR) 60.3 (50.6, 70.2) 60.5 (46.8, 70.2) 0.34\nAge category, n (%) 0.01\n18-49 years 85 (24.1%) 767/2564 (29.9%)\n50-64 years 141 (40.1%) 817/2564 (31.9%)\n≥65 years 126 (35.8%) 980/2564 (38.2%)\nFemale sex assigned at birth, n (%) 167/350 (47.7%) 1147/2558 (44.8%)\nRace, n (%) <0.01\nWhite 198 (56.2%) 1771 (69.0%)\nBlack 145 (41.2%) 703 (27.4%)\nAsian 1 (0.3%) 38 (1.5%)\nAmerican Indian/Native \nAlaskan2 (0.6%) 14 (0.5%)\nNative Hawaiian/Pacific Islander2 (0.6%) 6 (0.2%)\nOther 6 (1.7%) 54 (2.1%)\nEthnicity, n (%) 0.95\nNot Hispanic 328 (93.2%) 2394 (93.3%)\nHispanic 14 (4.0%) 94 (3.7%)\nUnknown 10 (2.8%) 77 (3.0%)7\nPublic\nCharacteristic Pneumonia with \nS. pneumoniae detected \n(n= 352)Pneumonia without \nS. pneumoniae detected\n(n= 2565)P-value\nType of home before illness, n (%) 0.27\nCommunity dwelling 320 (90.9%) 2382 (92.9%)\nNursing Home 6 (1.7%) 43 (1.7%)\nAssisted Living 6 (1.7%) 33 (1.3%)\nRehabilitation hospital 1 (0.3%) 13 (0.5%)\nSchool housing 0 (0.0%) 0 (0.0%)\nHomeless/shelter 12 (3.4%) 40 (1.6%)\nOther 3 (0.9%) 33 (1.3%)\nUnknown 4 (1.1%) 21 (0.8%)\nEver regularly smoked tobacco, n (%) 205/349 (58.7%) 1232/2554 (48.2%) <0.01\nAlcohol use >3 days/week, n (%) 30/348 (8.6%) 145/2543 (5.7%) 0.03\nUse of opioids at least weekly, n (%) 68/339 (20.1%) 438/2462 (17.8%) 0.31\nInteracts with child <5 years old at \nleast once per week, n (%)122/340 (35.9%) 682/2468 (27.6%) <0.01\nLives with children, n (%) 83/346 (24.0%) 517/2534 (20.4%)Patient Characteristics: Social History\n8\nPublic\nCharacteristic Pneumonia with \nS. pneumoniae detected \n(n= 352)Pneumonia without \nS. pneumoniae detected\n(n= 2565)P-value\nChronic medical conditions, n (%)\nDementia 11/349 (3.2%) 65/2528 (2.6%) 0.362\nCOPD 97/346 (28.0%) 487/2510 (19.4%) <0.001\nAsthma 72/346 (20.8%) 474/2518 (18.8%) 0.413\nHeart failure 61/340 (17.9%) 446/2509 (17.8%) 0.824\nPrior MI 37/344 (10.8%) 231/2525 (9.1%) 0.359\nPrior stroke 38/347 (11.0%) 255/2516 (10.1%) 0.651\nEnd stage kidney disease with \nchronic kidney replacement14/342 (4.1%) 125/2515 (5.0%) 0.424\nDiabetes mellitus 82/348 (23.6%) 684/2525 (27.1%) 0.159\nChronic liver disease 30/343 (8.7%) 173/2508 (6.9%) 0.254\nImmunosuppression 72/343 (21.0%) 529/2499 (21.2%) 0.983\nSolid organ cancer 80/348 (23.0%) 589/2501 (23.6%) 0.981\nHematologic cancer 30/346 (8.7%) 193/2511 (7.7%) 0.598\nSolid organ transplant 25/347 (7.2%) 205/2528 (8.1%) 0.545\nPregnant 0/348 (0.0%) 22/2533 (0.9%) 0.081\nObesity with body mass index \n>30 kg/m289/355 (25.9%) 1009/2479 (40.7%) <0.001Patient Characteristics: Chronic Medical Conditions \n9\nPublic\nCharacteristic Pneumonia with \nS. pneumoniae detected \n(n= 352)Pneumonia without \nS. pneumoniae detected\n(n= 2565)P-value\nReceived antibiotics for current illness before \nhospitalization, n (%)71/328 (21.6%) 613/2297 (26.7%) 0.05\nDuration of acute illness prior to hospital admission [days], median (IQR)2.6 (1.3, 5.0) 2.7 (1.1, 5.7) 0.36\nCURB- 65* score at hospital admission, n (%) 0.17\n0 (low risk) 123/345 (35.7%) 943/2523 (37.4%)\n1 (low risk) 126/345 (36.5%) 869/2523 (34.4%)\n2 (moderate risk) 60/345 (17.4%) 547/2523 (21.7%)\n3 (high risk) 31/345 (9.0%) 150/2523 (5.9%)\n4 (high risk) 5/345 (1.4%) 14/2523 (0.6%)\n5 (high risk) 0/345 (0.0%) 0/2523 (0.0%)\nTiming of Enrollment <0.01\nBefore COVID- 19 in US (October 2018 – \nFebruary 2020)231/345 (67.0%) 1249/2519 (49.6%)\nAfter COVID- 19 in US (March 2020 – \nOctober 2022)114/345 (33.0%) 1270/2519 (50.4%)Patient Characteristics: Acute Illness\n10* CURB -65: pneumonia severity scoring system, consisting of the following variables: confusion, uremia, respiratory rate, blood pressure, age >65\nPublic\nBinaxNOW\n125 patients positive\nCultures\n56 patients positive44 53 SSUAD\n283 patients positive 199\n1117523352 Patients with ≥1 Positive Pneumococcal Test\n12Percentage of Pneumococcal Serotype Detections\n14.6%\n9.8%\n7.0%\n6.0%5.7%5.4%5.1%4.7%4.1%3.5%3.2%2.8%2.2%1.9%1.6%1.3%0.9% 0.3% 0.0%\nn=46 n=31 n=22 n=19 n=18 n=17 n=16 n=15 n=13 n=11 n=10 n=9 n=7 n=6 n=5 n=4 n=3n=1n=0\n3 22F 19A 35B 9N 19F 23A 11A 23B 7F, 8, \n17F, 316A/C 16F, \n20A1, 5 9V, 15C 15A 33F 4, 6B, \n24F14, 10A, \n12F18C,  \n23F\nSerotype316 serotypes detected by SSUAD (denominator) among 283 unique patients\n13Vaccine Category Pneumococcal serotypes% of serotypes in adults \nhospitalized with CAP \n(n=2917)\nV116 (21 serotypes) 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15C, 16F, 17F, 19A, 20A, 22F, 23A, 23B, 24F, 31, 33F, 35B 9.3%\nPCV20  (19 serotypes; serotype 15B not tested) 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 18C, 19A, 19F, 22F, 23F, 33F 6.7%\nPCV15  (15 serotypes) 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, 33F 5.8%\nV116 and not PCV15 or PCV20 (11 serotypes) 9N, 15A, 15C, 16F, 17F, 20A, 23A, 23B, 24F, 31, 35B 4.1%8.0%11.3%\n8.7%\n4.7%8.4%\n6.9%\n4.0%7.3%\n5.8%\n4.0%4.8%\n3.1%\n0%2%4%6%8%10%12%\n18-49 years old (n=852) 50-64 years old (n=958) 65+ years old (n=1107)% of patients with ≥1 serotype in categoryV116 PCV20 PCV15 11 unique V116 serotypesPercentage of Pneumococcal Serotype by Vaccine in Adults Hospitalized with CAP\nPublic\nConclusions\n•Pneumococcal CAP remains a major cause of adult hospitalizations\n•SSUAD assays greatly increase S. pneumoniae detection over traditional testing\n•Among adults hospitalized with CAP:\n•12.1% with S. pneumoniae detected\n•9.3% with a pneumococcal serotype in V116\n•4.1% with a serotype unique to V116 (not PCV15 or PCV20)\n•Most commonly detected serotypes unique to V116: 35B, 9N, 23A, 23B\n14", "summary": "Public Interim Results from the PNEUMO Study .  Pneumococcal pNeumonia Epidemiology, Urine serotyping, and  Mental Outcomes study February 29, 2024 Study Leadership Wesley H. Self, MD Vanderbilt UniversityJ. Jackson Resser , MS Vanderbilt UniversityKelly D. Johnson, PhDMerck & Co., Inc. 1 Funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USANadine Rouphael , MD Emory University Public PNEUMO study overview •Adults 18+ years hospitalized with  community acquired…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-28-29-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-02-28-29/03-Pneumococcal-Self-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 14}
{"title": "04 Pneumococcal Platt 508", "content": "V116: An Investigational Adult Specific Pneumococcal \nConjugate Vaccine\nKey Results from the Phase 3 Clinical Development Program\nACIP Meeting, 29 -Feb -2024\nHeather Platt, M.D., on behalf of the V116 team\nDistinguished Scientist, Global Clinical Development\nMerck Research Laboratories\nMerck & Company, Inc.\nPresentation Rationale for Development of V116\n Overview of V116 Adult Clinical Development Program\n Immunogenicity Results\n•Vaccine naïve adults ≥18 years of age\n•Vaccine experienced adults ≥50 years of age\nIntegrated Summary of Safety\n•Vaccine naïve and vaccine experienced adults ≥18 years of age\n Supportive Studies\n•V116 in individuals living with HIV\n•V116 administered with concomitant influenza vaccine\n•V116 lot consistency\n Conclusions\n Questions\n2\nConfidential\nThe introduction of PCVs has significantly decreased disease incidence \nin children and changed epidemiology of IPD in adults in the US\n387.6\n1.85.9\n5.3\n020406080100\nPre-PCV Post-PCV\nPCV13 Non PCV13\n*Centers for Disease Control and Prevention, IPD serotype data 2019, as compiled from data provided through Active Bacterial Core surveillance (ABCs). IPD cases per 100K in US by serotype, children <5\n94\n7IPD cases per 100K in US by serotype, adults ≥65\n45.9\n5.415.1\n18.6\n020406080100\nPre-PCV Post-PCV\nPCV13 Non PCV1361\n24\nConfidential\nRationale for Development of V116\n4\n The burden of disease in adults remains high; IPD due to non -\nvaccine serotypes has increased in adults. \nV116 being developed as a  population -specific  vaccine to prevent invasive \ndisease and pneumonia in adults. \nV116 is designed to  complement PCV pediatric immunization \nprograms.  PCV use in infants has significantly decreased the burden of \ndisease in adults  through indirect protection .\nPopulation -specific \nvaccinationUnmet medical need \nin adultsIndirect protection \nthrough pediatric vaccination\nComplementary to\n pediatric PCVs\nV116 is an adult specific  pneumococcal conjugate vaccine (PCV)\nIPD, invasive pneumococcal disease; PCV, pneumococcal conjugate vaccine; PCV13, pneumococcal conjugate vaccine, 13 -valent; PCV15  pneumococcal conjugate vaccine, 15 -valent, PCV20, pneumococcal conjugate vaccine, 20 -valent.\n1. CDC , IPD Serotype Data 2019, as compiled from data provided through Active Bacterial Core surveillance (ABCs). \n2. 2. Platt H , Omole T, Cardona J, Fraser NJ, Mularski  RA, Andrews C, Daboul  N, Gallagher N, Sapre A, Li J, Polis A, Fernsler D, Tamms G, Xu W, Murphy R, Skinner J, Joyce J, Musey  L. Safety, tolerability, and immunogenicity of a 21 -valent pneumococcal \nconjugate vaccine, V116, in healthy adults: phase 1/2, randomised , double -blind, active comparator -controlled, multicentre , US -based trial. Lancet Infect Dis. 2023 Feb;23(2):233 -246. https://pubmed.ncbi.nlm.nih.gov/36116461/  \n15C is denoted here to represent the serotype protection proposed with deOAc15B as the molecular structures for deOAc15B and 15C are similar (Jones C, Lemercinier  X. 2005. Full NMR assignment and revised structure for the capsular polysaccharide from \nStreptococcus pneumoniae type 15B. Carbohydr  Res 340:403 –409.) •Includes 21 pneumococcal serotypes , 4µg/PnPs individually conjugated to CRM197 formulated without an adjuvant\n•Single dose, 0.5mL pre-filled syringe , intramuscular injection for adults 18+\n•The serotypes in V116 accounted for ~85% of IPD and the 8 unique serotypes accounted for  ~30% of IPD in US \nadults ≥65 years in 2019\n•V116 is currently under Priority Review by the FDA for the prevention of IPD and pneumonia in adults  ≥18 years of \nage with target action date of June 17, 2024.\nSerotype Composition\nPCV13 4 6B 9V 14 18C 19F 23F 1 3 5 6A 7F 19A\nPCV15 4 6B 9V 14 18C 19F 23F 1 3 5 6A 7F 19A 22F 33F\nPPSV23 4 6B 9V 14 18C 19F 23F 1 3 5 7F 19A 22F 33F 2 8 9N 10A 11A 12F 15B 17F 20\nPCV20 4 6B 9V 14 18C 19F 23F 1 3 5 6A 7F 19A 22F 33F 8 10A 11A 12F 15B\nV116 3 6A 7F 19A 22F 33F 8 9N 10A 11A 12F 17F 20A 15A 15C 16F 23A 23B 24F 31 35B\n5Confidential\nSource: US Centers for Disease Control and Prevention, IPD serotype data 2019, as compiled from data provided through Active Bac terial Core surveillance (ABC).In adults 50 –64 and ≥65 years of age, serotypes in V116 are responsible for the \nmajority of residual IPD in adults\nIPD coverage (% of serotypes and cases per 100,000) in US Adults 50 –64 and ≥65 years of age, 2019\n38.9%55.5%67.9% 67.7%83.4%\n40.2%52.9%60.2% 60.0%84.8%\nPCV15 PCV20 PCV24 PPSV23 V116\nPCV15 V116 PPSV23 PCV24 PCV20≥65~6 cases ~9 cases ~11 cases ~11 cases ~13 cases ~9 cases ~12 cases ~14 cases ~14 cases ~20 cases\n50-64 50-64 50-64 50-64 50-64 ≥ 65 ≥ 65 ≥ 65 ≥ 65\n6\nV116 Phase 3 Clinical \nDevelopment Program\n7\nConfidential\nV116 Clinical Development Program focused on enrolling participants at \nrisk for pneumococcal disease\n8V116 -007\nHigh Risk (HIV)\n(n=300)V116 -008\nAt-Risk Adults\n(n=900)V116 -P004\n Clinical Lot  Consistency\n(n=2040)V116 -P003\nPivotal\n(n=2600)V116 -P005 \nConcomitant Flu\n(n=1000)V116 -P006\nVaccine Experienced\n(n=700)\n≥ 18 years old 18 – 64 years old18 – 49 years old ≥ 50 years old ≥ 18 years old\nV116 -013\nPediatric with Increased Risk\n(n=820)\n≥ 2 - <18 years old\nConfidential\n4 Studies in the V116 BLA submission represent a broad, \ndiverse patient population \n9V116 -007\nHigh Risk (HIV)\n(n=300)V116 -008\nAt-Risk Adults\n(n=900)V116 -P004\n Clinical Lot  Consistency\n(n=2040)V116 -P003\nPivotal\n(n=2600)V116 -P005 \nConcomitant Flu\n(n=1000)V116 -P006\nVaccine Experienced\n(n=700)\n≥ 18 years old 18 – 64 years old18 – 49 years old ≥ 50 years old ≥ 18 years old\nV116 -013\nPediatric with Increased Risk\n(n=820)\n≥ 2 - <18 years old\n\nConfidential\nSafety Endpoints Immunogenicity Endpoints\nOPA responses supported primary objectives:\n•Serotype specific OPA Geometric Mean Titers (GMTs) \n•Proportion of participants with ≥4-fold rise in OPA \nresponses from baseline to Day 30 postvaccination\nOPA and IgG responses supported secondary objectives:\n•Serotype specific IgG Geometric Mean Concentrations \n(GMCs)\n•Proportion of participants with ≥4-fold rise in IgG \nresponses from baseline to Day 30 postvaccination\n•Geometric Mean Fold Rise (GMFR) of OPA and IgG \nresponses\n•Reverse Cumulative Distribution Curves (RCDCs) for \nOPA and IgG responsesImmunogenicity & Safety Endpoints in the V116 Program\nParticipants reported adverse events on an electronic vaccine report \ncard.Primary Safety Endpoints:\n•Solicited injection site events Day 1 -5 \npostvaccination: erythema, swelling, injection -site \npain\n•Solicited systemic events Days 1 -5 postvaccination: \nheadache, myalgia, fatigue\n•Serious vaccine -related events Day 1 through the \nduration of participation in the study\nAdditional Safety Endpoints:\n•Unsolicited AEs, Vaccine related AEs, Any SAE\n•Maximum temperature Day 1 -5 postvaccination\nImmune responses were assessed in validated multiplex \nopsonophagocytic (OPA) and electrochemiluminescence (ECL IgG) \nassays 10\n¹Weber Shandwick/KCR Research, 2020 / AMO 2019V116 -003A Phase 3, Randomized, Double -blind, Active \nComparator -controlled Clinical Study to \nEvaluate the Safety, Tolerability, and \nImmunogenicity of V116 in Pneumococcal \nVaccine -naïve Adults\n11\nConfidential\nV116 -003 Study Design\nV116  or  PCV20\nPrevaccination\nImmunogenicity\n(Day 1)\neVRC , solicited AEs\nSerious and nonserious AEs  Serious AEs \nPostvaccination\nImmunogenicity\n(Day 30)Cohort 1 ( ≥50 years of age)\nN=2362 Participants\nrandomized 1:1,V116 to PCV20\n(Stratified by age: 50 -64, 65 -74, 75 -84, ≥85)\nCohort 2 (18 -49 years of age)\nN=301 Participants\nrandomized 2:1,V116 to PCV20\nImmunogenicity \nassessment\nSafety \nassessmentDay 1 Day 5 Day 7 Day 90 Day 30 Month 6Pivotal Study\n1 3 2 4 5\n12\nV116 -003: Primary study objectives\nPrimary safety Primary immunogenicity\nIn adults ≥50 years:\n•Demonstrate that V116 is noninferior  to PCV20 for\n10 common serotypes\n–Lower bound of the 2 -sided 95% CI of the OPA GMT ratio \n(V116/PCV20) to be >0.5\n•Demonstrate that V116 is superior  to PCV20 for\n11 unique serotypes\n–Lower bound of the 2 -sided 95% CI of the OPA GMT ratio \n(V116/PCV20) to be >2.0\n–2-sided 95% CI of the differences (V116 – PCV20) between the \nproportions of participants with a ≥4-fold rise to be >10%\nIn adults 18 –49 years:\n•Demonstrate V116 immunobridges  to adults 50 -64 \nyears of age for 21 serotypes in V116\n–Lower bound of the 2 -sided 95% CI of the OPA GMT ratio \n(V116 18 -49/V116 50 –64 years ) to be >0.5•To evaluate the safety and tolerability of V116 as \nassessed by the proportion of participants with adverse \nevents (AEs)\n–Solicited injection site events Day 1 –5 postvaccination: \nerythema, swelling, injection -site pain\n–Solicited systemic events Days 1–5 postvaccination: \nheadache, myalgia, fatigue\n–Serious vaccine -related events Day 1 through the duration of \nparticipation in the studyPivotal Study\n13\nConfidential\nV116 -003 Baseline Characteristics\nIn each cohort, baseline characteristics were balanced between the treatment groups \nRisk Factors includes prespecified medical history conditions: Alcoholism, Chronic Heart Disease, Chronic Kidney Disease, Chr onic Liver Disease, Chronic Lung Disease, Diabetes, Smoking.14Cohort 1 (Age ≥50 years) Cohort 2 (Ages 18 -49 years)\nV116, N=1179 PCV20, N=1177 V116, N=200 PCV20, N=100\nSex\nFemale 687 (58.3) 670 (56.9) 137 (68.5) 64 (64.0)\nAge ( yr)\nMedian (min to max) 65 (50 -91) 65 (50 -97) 36 (18 -49) 34 (18 -49)\n18-49, n (%) 0 (0) 0 (0) 200 (100) 100 (100)\n50 to 64, n (%) 589 (50.0) 587 (49.9) 0 (0) 0 (0)\n65 to 74, n (%) 464 (39.4) 464 (39.4) 0 (0) 0 (0)\n75-84, n (%) 112 (9.5) 113 (9.6) 0 (0) 0 (0)\n≥85, n (%) 14 (1.2) 13 (1.1) 0 (0) 0 (0)\nRace\nAsian 148 (12.6) 168 (14.3) 38 (19.0) 15 (15.0)\nBlack or African American 116 (9.8) 115 (9.8) 13 (6.5) 14 (14.0)\nMultiple 26 (2.2) 30 (2.5) 9 (4.5) 6 (6.0)\nWhite 867 (73.5) 844 (71.7) 139 (69.5) 62 (62.0)\nOther 21 (1.8)  19 (1.6) 1 (0.5) 3  (3.0)\nEthnicity\nHispanic or Latino 259 (22.0) 242 (20.6) 58 (29.0) 24 (24.0)\nPneumococcal Risk Factors\n1 Risk Factor 347 (29.4) 328 (27.9) 45 (22.5) 18 (18.0)\n2 or More Risk Factors 100 (8.5) 81 (6.9) 3 (1.5) 1 (1.0)Pivotal Study\nConfidential\nPneumococcal\nserotypeV116 PCV20 GMT ratio\nn GMT n GMT (95% CI)\n3 1154 274.0 1161 176.7 1.55 (1.40, 1.72)\n6A 1148 2,302.0 1153 2,972.5 0.77 (0.68, 0.88)\n7F 1152 3,637.4 1158 3,429.9 1.06 (0.95, 1.18)\n8 1155 2,501.3 1158 1,811.1 1.38 (1.25, 1.53)\n10A 1161 3,893.4 1159 4,678.0 0.83 (0.75, 0.93)\n11A 1145 3,232.6 1150 2,092.8 1.54 (1.39, 1.72)\n12F 1160 2,641.2 1161 2,499.6 1.06 (0.92, 1.21)\n19A 1159 2,136.1 1162 2,817.8 0.76 (0.69, 0.84)\n22F 1147 3,874.5 1154 4,770.1 0.81 (0.72, 0.92)\n33F 1154 13,558.9 1157 11,742.1 1.15 (1.01, 1.32)•V116 is noninferior to PCV20 \nfor the 10 common serotypes.\n•The lower bounds of the two -\nsided 95% confidence \nintervals (CIs) are greater \nthan 0.5 for all 10 common \nserotypes.Primary immunogenicity objectiveV116 -003  Cohort 1: ≥50 years of age\nV116 is noninferior to PCV20 for the 10 common serotypes \nPostvaccination OPA GMT Ratios for Common Serotypes\n0.5 1.0 2.0\nGMT ratio log10 scale (V116/PCV20)\n15Pivotal Study\nConfidential\n•V116 is superior to PCV20 for \n10 of 11 unique serotypes in \nV116.\n•The lower bounds of the two -\nsided 95% CIs are >2.0 for 10 \nof 11 unique serotypes in V116. \n•For serotype 15C, the lower \nbound of the 95% CI is 1.77.Primary immunogenicity objectivePostvaccination OPA GMT Ratios for Unique Serotypes\nPneumococcal\nserotypeV116 PCV20 GMT ratio\nn GMT n GMT (95% CI)\n9N 1147 7,470.7 1150 1,640.4 4.55 (4.12, 5.04)\n15A 1107 5,237.2 1102 1,589.0 3.30 (2.91, 3.74)\n15C 1153 4,216.2 1158 2,072.3 2.03 (1.77, 2.34)\n16F 1151 4,868.2 1153 846.3 5.75 (5.16, 6.41)\n17F 1148 7,764.9 1156 460.4 16.86 (14.90, 19.09)\n20A 1161 6,099.2 1155 631.1 9.66 (8.66, 10.79)\n23A 1132 3,737.2 1104 461.5 8.10 (6.86, 9.55)\n23B 1160 1,082.5 1160 107.3 10.09 (8.48, 12.00)\n24F 1153 2,728.6 1130 70.5 38.71 (33.87, 44.25)\n31 1153 3,132.5 1154 144.4 21.69 (18.68, 25.18)\n35B 1153 8,527.8 1159 1,383.0 6.17 (5.59, 6.80)\nGMT ratio log10 scale (V116/PCV20)1 0.5 2 4 8 16 32 64V116 -003  Cohort 1: ≥50 years of age\nV116 is superior to PCV20 for 10 of 11 unique serotypes\n16Pivotal Study\nSuperiority criteria met if the lower bound of the 95% CI is >2.0\nConfidential\n•V116 is superior to PCV20 \nfor 10 of 11 unique \nserotypes in V116.\n•The lower bounds of the \n2-sided 95% CIs are > 10 \npercentage points for 10 \nof 11 serotypes.Primary immunogenicity objectiveProportions of Participants With a ≥4-Fold Rise in OPA \nResponses for Unique Serotypes64.7%\n66.7%\n83.4%\n71.9%\n75.8%\n67.3%\n78.9%\n85.5%\n80.5%\n76.5%\n60.0%19.9%\n35.8%\n74.2%\n20.8%\n9.5%\n9.6%\n36.8%\n49.6%\n6.3%\n17.9%\n6.8%\n0%20%40%60%80%100%\n9N 15A 15C 16F 17F 20A 23A 23B 24F 31 35B% of participants with a ≥4-fold rise\nUnique serotype\nV116 (N=1179) PCV20 (N=1177)44.7% 30.9% 9.2% 51.1% 66.3% 57.7% 42.2% 35.9% 74.2% 58.6% 53.2%% difference [V116 – PCV20]\np=0.665(40.7. 48.6) (25.8, 35.8) (5.6, 12.9) (47.1, 54.9) (62.8, 69.6) (54.2, 61.1) (37.6, 46.6) (32.1, 39.6) (71.1, 77.1) (54.8, 62.1) (49.6, 56.6) V116 -003  Cohort 1: ≥50 years of age\nV116 is superior to PCV20 for 10 of 11 unique serotypes \n17Pivotal Study\nConfidential\nV116 -003  Cohort 1: ≥50 years of age\nV116 elicits robust cross reactive antibody responses to serotype 15B\n18V116 includes serotype 15C \nand elicited cross -reactive \nimmune responses to 15B0%20%40%60%80%100%\nV116 (N=1179) PCV20 (N=1177)% of participants with a ≥4-fold rise in OPA \nresponsesSerotype 15BPivotal Study\nPCV20 includes \nserotype 15B64.6%\n(61.3, 67.8) 64.7%\n(61.4, 67.8)\nConfidential\n•V116 in participants 18 to 49 \nyears of age immunobridges  \nto V116 in participants 50 to \n64 years of age for the 21 \nserotypes in V116.\n•The lower bound of the two -\nsided 95% CIs is  >0.5 for all \n21 serotypes in V116.Primary immunogenicity objective\nPneumococcal\nserotypeV116\n18–49 years\n(N = 200)V116\n50–64 years\n(N = 589)GMT ratioa\n(V116 18 –49 years/ \nV116 50–64 years)\nn GMT n GMT (95% CI)\n3 194 308.6 572 282.7 1.09 (0.90, 1.33)\n6A 196 5,289.6 569 2,572.9 2.06 (1.61, 2.62)\n7F 198 6,447.2 571 4,278.8 1.51 (1.23, 1.84)\n8 197 4,516.0 571 3,004.7 1.50 (1.26, 1.79)\n9N 197 17,283.2 570 8,791.4 1.97 (1.59, 2.43)\n10A 197 6,808.1 575 4,382.6 1.55 (1.26, 1.92)\n11A 196 5,871.6 564 3,785.8 1.55 (1.26, 1.91)\n12F 196 6,150.4 574 3,561.2 1.73 (1.37, 2.17)\n15A 184 11,319.2 550 5,901.2 1.92 (1.55, 2.37)\n15C 195 10,194.0 570 5,708.0 1.79 (1.36, 2.35)\n16F 193 8,877.0 571 5,720.0 1.55 (1.26, 1.91)\n17F 194 16,070.6 568 10,068.0 1.60 (1.26, 2.02)\n19A 198 2,773.2 574 2,374.6 1.17 (0.97, 1.40)\n20A 197 13,150.0 575 7,562.7 1.74 (1.39, 2.18)\n22F 198 9,299.6 568 4,683.6 1.99 (1.58, 2.49)\n23A 192 8,848.7 561 4,739.5 1.87 (1.43, 2.44)\n23B 198 2,140.1 575 1,420.9 1.51 (1.11, 2.04)\n24F 197 4,137.6 570 3,047.2 1.36 (1.10, 1.67)\n31 195 8,005.6 570 3,820.7 2.10 (1.63, 2.69)\n33F 197 34,805.5 570 17,607.4 1.98 (1.52, 2.57)\n35B 198 13,933.4 573 9,053.9 1.54 (1.26, 1.87)\nGMT ratio log10 scale (V116 18 -49/V116 50 -64)1 0.5 2 4V116 -003:  Cohort 2: 18-49 years of age\nV116 immunobridges to participants 50 -64 years of age for all 21 serotypes\n19Pivotal Study\n¹Weber Shandwick/KCR Research, 2020 / AMO 2019V116 -006V116 -006: A Phase 3 Clinical Study to Evaluate \nthe Safety, Tolerability, and Immunogenicity of \nV116 in Pneumococcal Vaccine -Experienced \nAdults 50 Years of Age or Older\n20\nConfidential\nCohort  1 : Prior PPSV23 only\nN=300; Randomized 2:1 (V116:PCV15)V116 -006 Study Design\nVisit\nTime Day 1\nScreening/vaccination1 3\nV116Day 7 Day 90 Day 1802 4 5\nCohort  2 : Prior PCV13 only\nN=300; Randomized 2:1 (V116:PPSV23)\nCohort  3 : Prior PCV15, PCV20, PCV13+PPSV23,\nPCV15+PPSV23 or PPSV23+PCV13\nN=100; Open -label V116Day 30\nV116V116or\norPCV15\nPPSV23\nPrevaccination\nImmunogenicity\n(Day 1)\neVRC , solicited AEs\nSerious and nonserious AEs Serious AEs \nPostvaccination\nImmunogenicity\n(Day 30)\nParticipants used an electronic Vaccine Report Card ( eVRC ) to report solicited AEs Days 1 -5 postvaccination and other AEs through Day 30 postvaccination21Vaccine -experienced\nImmunogenicity \nassessment\nSafety \nassessment\nConfidential\nIn adults ≥50 years: \nTo evaluate the serotype -specific opsonophagocytic activity \n(OPA) geometric mean titers (GMTs) at 30 days postvaccination \nfor all serotypes included in V116V116 -006 Primary study objectivesVaccine -experienced\nPrimary safety Primary immunogenicity\n•To evaluate the safety and tolerability of V116 as \nassessed by the proportion of participants with adverse \nevents (AEs)\n–Solicited injection site events Day 1 –5 postvaccination: \nerythema, swelling, injection -site pain\n–Solicited systemic events Days 1–5 postvaccination: \nheadache, myalgia, fatigue\n–Serious vaccine -related events Day 1 through the duration of \nparticipation in the study\n22\nConfidential\nV116 -006 Participant Characteristics\nEnrollment is balanced in each cohort and reflects the pneumococcal vaccination history\n23Cohort 1 (prior PPSV23) Cohort 2 (prior PCV13) Cohort 3\nV116\nN=229PCV15\nN=119V116\nN=174PPSV23\nN=85V116\nN=105\nSex\nMale 112 (48.9) 59 (49.6) 74 (42.5) 36 (42.4) 50 (47.6)\nFemale 117 (51.1) 60 (50.4) 100 (57.5) 49 (57.6) 55 (52.4)\nAge ( yr)\n50 to 64 48 (21.0) 25 (21.0) 80 (46.0) 39 (45.9) 17 (16.2)\n≥65 181 (79.0) 94 (79.0) 94 (54.0) 46 (54.1) 88 (83.8)\nMean ±SD 68.7 ±7.5 69.0 ±7.1 65.5 ±7.8 65.4 ±6.6 71.0 ±7.6\nMedian (range) 69.0 (50 to 86) 69.0 (51 to 88) 66.0 (50 to 83) 65.0 (51 to 81) 71.0 (53 to 91)\nRace\nAsian 96 (41.9) 47 (39.5) 55 (31.6) 25 (29.4) 13 (12.4)\nBlack or African American 6 (2.6) 3 (2.5) 3 (1.7) 1 (1.2) 6 (5.7)\nMultiple 2 (0.9) 0 (0.0) 0 (0.0) 0 (0.0) 1 (1.0)\nWhite 125 (54.6) 69 (58.0) 116 (66.7) 59 (69.4) 85 (81.0)\nEthnicity\nHispanic or Latino 21 (9.2) 17 (14.3) 34 (19.5) 16 (18.8) 14 (13.3)\nTime since last pneumococcal \nvaccination\n1 to 4 years 108 (47.2) 54 (45.4) 135 (77.6) 66 (77.6) 78 (74.3)\n5 to 9 years 85 (37.1) 45 (37.8) 33 (19.0) 18 (21.2) 27 (25.7)\n≥10 years 36 (15.7) 20 (16.8) 6 (3.4) 1 (1.2) 0 (0.0)Vaccine -experienced\nConfidential\nV116 -006 Cohort 1: ≥50 years of age who previously received PPSV23\nV116 elicits comparable immune responses to PCV15; higher immune responses for serotypes unique to V116\n2402,0004,0006,0008,000\n8 9N 10A 11A 12F 15A 15C 16F 17F 20A 23A 23B 24F 31 35BObserved GMTUnique serotypes\nV116 (N=229) PCV15 (N=119)02,0004,0006,0008,000\n3 6A 7F 19A 22F 33FObserved GMTCommon serotypes\nV116 (N=229) PCV15 (N=119)Vaccine -experienced\nConfidential\nV116 -006 Cohort 2: ≥50 years of age who previously received PCV13\nV116 elicits comparable immune responses to PPSV23; higher immune responses for serotypes unique to V116\n2502,5005,0007,50010,00012,500\n3 7F 8 9N 10A 11A 12F 17F 19A 20A 22F 33FObserved GMTCommon serotypes\nV116 (N=174) PPSV23 (N=85)02,5005,0007,50010,00012,500\n6A 15A 15C 16F 23A 23B 24F 31 35BObserved GMTUnique serotypes\nV116 (N=174) PPSV23 (N=85)Vaccine -experienced\nConfidential\n*Prior PCV13+PPSV23 [n=45], PCV15+PPSV23 [n=5], PPSV23+PCV13 [n=54], PCV15 [n=1], or PCV20 [n=0] 02,0004,0006,0008,000\n3 6A 7F 8 9N 10A 11A 12F 15A 15C 16F 17F 19A 20A 22F 23A 23B 24F 31 33F 35BObserved GMT\n05001,000\nSerotype 3Observed GMTcohort 1 cohort 2 cohort 3V116 -006 Cohort 3: ≥50 years of age who previously received other pneumococcal vaccine(s)* \nV116 is immunogenic in individuals who previously received a pneumococcal vaccine\n26Participants who received V116Vaccine -experienced\nIntegrated Summary of Safety\n27Integrated Analysis of Safety in the \nPhase 3 Clinical Development Program\nConfidential\nV116 is well tolerated in adults ≥18 years of age with a safety profile comparable to \ncurrently licensed pneumococcal vaccines\n28a Only participants from V116 -005 vaccinated with V116 in the sequential group are included in the V116 group. \nbControl  group includes participants vaccinated with PCV15, PCV20, or PPSV23\ncAs determined by the investigator; all injection site adverse events are assessed as vaccine -related\nd6 deaths in the V116 group in the Integrated Safety Summary; 7 deaths in the V116 group across the Phase 3 studies when the c oncomitant group from P005 is included. Adverse Event Summary\n(V116 -003, V116 -004, V116 -005a, V116 -006) V116 \n(N=4,020)Control b\n(N=2,018)\nn (%) n (%) \nWith adverse events (Day 1 –30) 2695 (67.0) 1386 (68.7)\nWith vaccine -related adverse events (Day 1 -30)c2555 (63.3) 1297 (64.3)\nSolicited 2516 (62.6) 1279 (63.4)\nUnsolicited 313 (7.8) 123 (6.1)\nwith SAEs (Day 1 -Day 30)                        14                                      (0.3)                                    7                                       (0.3)                                    \nwith vaccine -related SAEs (Day 1 -Day 30)                   2                                       (0.0)                                    0                                       (0.0)                                    \nwith SAEs within 30 minutes postvaccination                                          1                                       (0.0)                                    0                                       (0.0)                                    \nWho diedd6                                       (0.1)                                    3                                       (0.1)                                    \nwith vaccine -related deathsc0 (0.0) 0 (0.0)Integrated Safety\nSolicited events include erythema, injection site pain, injection site swelling, fatigue, headache, and myalgia were solicite d from Day 1 through Day 5 postvaccination. Pyrexia was defined as \ntemperature ≥100.4 °F (38.0 C) solicited from Day 1 through Day 5 postvaccination.Frequency and intensity of solicited adverse events were comparable in V116 and control groups\nSolicited adverse events by intensity (%)\n0%10%20%30%40%50%60%\nV116 Control V116 Control V116 Control V116 Control V116 Control V116 Control V116 ControlPotentially Life-threatening (Grade 4)\nSevere (Grade 3)\nModerate (Grade 2)\nMild (Grade 1)\nInjection site \nerythemaInjection site pain Injection site \nswellingFatigue Myalgia Headache PyrexiaIntegrated Safety\nV116, n= 4,020      Control, n=2,018Majority of events were \n≤3 days in duration\n29\nPhase 3 Supportive Studies\n30V116 -007: V116 in Adults Living with HIV\nV116 -005: V116 with Concomitant Quadrivalent Influenza Vaccine (QIV)\nV116 -004: V116 Lot Consistency\nConfidential\n02,0004,0006,0008,00010,00012,00014,000\n15A 15C 16F 23A 23B 24F 31 35BObserved GMTUnique serotypes\nV116 + Placebo (N = 156) PCV15 + PPSV23 (N = 156)04,0008,00012,00016,00020,000\n3 6A 7F 8 9N 10A 11A 12F 17F 19A 20A 22F 33FObserved GMTCommon serotypes\nV116 + Placebo (N = 156) PCV15 + PPSV23 (N = 156)V116 -007: In adults living with HIV, V116 elicits comparable immune responses \nto PCV15+PPSV23, & higher immune responses for unique serotypesAdults Living with HIV\n31\nConfidential\nV116 -005: V116 elicits robust immune responses when administered \nconcomitantly with influenza vaccine\n32•V116 administered \nconcomitantly with influenza \nvaccine is noninferior to V116 \nadministered sequentially \nwith influenza vaccine for 20 \nof 21 serotypes\n•QIV administered \nconcomitantly is noninferior \nto QIV administered \nsequentially for 3 of 4 strains GMT ratio \nConcomitant/Sequential\n(95% CI)Pneumococcal \nserotype\n3 0.84 (0.72, 0.97)\n6A 0.79 (0.66, 0.94)\n7F 0.73 (0.63, 0.85)\n8 0.71 (0.61, 0.82)\n9N 0.67 (0.57, 0.79)\n10A 0.76 (0.65, 0.91)\n11A 0.64 (0.54, 0.75)\n12F 0.76 (0.62, 0.94)\n15A 0.71 (0.60, 0.85)\n15C 0.71 (0.58, 0.87)\n16F 0.69 (0.59, 0.81)\n17F 0.73 (0.62, 0.86)\n19A 0.75 (0.65, 0.85)\n20A 0.74 (0.63, 0.87)\n22F 0.77 (0.65, 0.91)\n23A 0.78 (0.63, 0.96)\n23B 0.56 (0.44, 0.72)\n24F 0.72 (0.61, 0.86)\n31 0.68 (0.56, 0.83)\n33F 0.84 (0.70, 1.01)\n35B 0.77 (0.67, 0.89)\n0.25 0.5 1 2\nGMT Ratio Log10 Scale\n(Concomitant Group/Sequential Group)Concomitant Influenza\n32\nConfidential\nV116 -004: V116 Immune responses were equivalent across 3 manufacturing lots \n33Pneumococcal \nserotypeV116 Lot 1 vs V116 Lot 2\nn1=(502 -527), n2=(505 -533)V116 Lot 1 vs V116 Lot 3\nn1=(502 -527), n2=(513 -533)V116 Lot 2 vs V116 Lot 3\nn1=(505 -533), n2=(513 -533)\n3\n6A\n7F\n8\n9N\n10A\n11A\n12F\n15A\n15C\n16F\n17F\n19A\n20A\n22F\n23A\n23B\n24F\n31\n33F\n35B\n0.5 2 0.5 2 0.5 2 1 1 1\nGMT Ratio Log10 Scale\nNote: dashed lines indicate the margins for the equivalence testLot Consistency\nPhase 3 Summary & \nConclusions\n34\nConfidential\nV116 Phase 3 Clinical Development Summary\n35In adults ≥18 years of age, who are pneumococcal vaccine -naïve and vaccine \nexperienced, with and without risk conditions:\n•V116 elicits robust immune responses to all 21 serotypes contained in the vaccine\n•V116 is noninferior to PCV20 for all common serotypes and superior to PCV20 for 10 of 11 \nserotypes unique to V116 in pneumococcal vaccine -naïve adults ≥50 years of age.\n•V116 is immunogenic in pneumococcal vaccine experienced adults , regardless of the prior \nvaccine received\n•V116 is immunogenic when administered concomitantly with inactivated influenza vaccine .\n•V116 is well -tolerated  with a safety profile generally comparable to currently licensed \npneumococcal vaccines. \nV116 is the first adult specific PCV with the potential for broad public health impact through the prevention of invasive dis ease \nand pneumonia due to S. pneumoniae .\nConfidential\nThank you\nSlide is intentionally blank", "summary": "V116: An Investigational Adult Specific Pneumococcal  Conjugate Vaccine Key Results from the Phase 3 Clinical Development Program ACIP Meeting, 29 -Feb -2024 Heather Platt, M.D., on behalf of the V116 team Distinguished Scientist, Global Clinical Development Merck Research Laboratories Merck & Company, Inc. Presentation Rationale for Development of V116  Overview of V116 Adult Clinical Development Program  Immunogenicity Results •Vaccine naïve adults ≥18 years of age •Vaccine experienced…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-28-29-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-02-28-29/04-Pneumococcal-Platt-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 37}
{"title": "05 Pneumococcal Moro 508", "content": "National Center for Emerging and Zoonotic Infectious Diseases\nPost -licensure safety surveillance of 20 -valent \npneumococcal conjugate vaccine (PCV20) \namong U.S. adults in the Vaccine Adverse \nEvent Reporting System (VAERS)\nPedro L. Moro, MD, MPH\nImmunization Safety Office\nDivision of Healthcare Quality Promotion Centers for Disease Control and Prevention (CDC)\nAdvisory Committee on Immunization Practices (ACIP)\nFebruary 29, 2024\nDisclaimer\nThe findings and conclusions in this presentation are \nthose of the author and do not necessarily represent the official position of the CDC\nThe use of product trade names is for identification purposes only\n2\nBackground on pre -l icensure safety of 20 -valent\npneumococcal conjugate vaccine (PCV20)\nAdverse events following PCV20 reported to the Vaccine\nA\ndverse Event Reporting System (VAERS)\nAdverse events of special interest: Guillain -Barr é\nSyndrome (GBS)\nSummary\n3Topics\nBackground: Pre -licensure clinical trials PCV20\n1 Pfizer’s Adult and Pediatric Clinical Trial Programs for 20 -Valent Pneumococcal Conjugate Vaccine Presented at IDWeek  2020. October 21, 2020.\n2 Kobayashi M, Farrar JL, Gierke R, et al. Use of 15 -Valent Pneumococcal Conjugate Vaccine and 20 -Valent Pneumococcal Conjugate V accine Among U.S. Adults: Updated Recommendations of the Advisory \nCommittee on Immunization Practices — United States, 2022. MMWR Morb  Mortal Wkly  Rep 2022;71:109 –117. DOI: http://dx.doi.org/10.15585/mmwr.mm7104a1  \n3 Prevnar20 vaccine insert https://www.fda.gov/vaccines -blood -biologics/vaccines/prevnar -20 Pre-licensure clinical trial data of PCV20 in adults has been reassuring\nSix randomized controlled trials in adults aged ≥ 18 years, which included more than \n6,000 participants1,2\nMost common adverse reactions were injection site pain, muscle pain, fatigue, headache, and joint pain\n2,3\nSerious adverse events (SAEs) balanced among vaccinees and controls2\nNo SAEs or deaths considered to be related to study vaccines3\nNo cases of Guillain -Barré Syndrome (GBS) identified in prelicensure studies2,3\n4\nIntroduction\nJune 8, 2021 –  PCV20 approved for adults aged ≥ 18 years \nby the FDA\nOctober 20, 2021 – ACIP recommendation\nPCV20 for adults aged ≥65\nPCV20 for adults aged 19– 64 years with underlying medical \nconditions\nFDA: Food and Drug Administration\nACIP: Advisory Committee on Immunization Practices\n5\nObjectives\nDescribe the safety profile of reports submitted to the\nV\naccine Adverse Event Reporting System (VAERS) following\nPCV20 in\nAdults aged ≥65 years\nAdults aged 19 –64 years\n6\nVAERS\nStrengths\nNational data \nAccepts reports from anyone\nRapidly detects safety signals \nCan detect rare adverse events\nData available to publicLimitations\nReporting bias \nInconsistent data quality and \ncompleteness\nLack of unvaccinated comparison group or denominator\nGenerally cannot assess causality\n•VAERS accepts all reports from all reporters without making judgments on \ncausality or judging clinical seriousness of the event\n•As a hypothesis generating system, VAERS identifies potential vaccine safety concerns that can be studied in more robust data systems\n7\nMethods – 1: PCV20\nSearched VAERS database for U.S. PCV20 reports during:\n•October 21, 2021 through December 31, 2023 for adults aged ≥ 19 years \n(19– 64 years and ≥ 65 years)\nSigns and symptoms of AEs coded using Medical Dictionary for Regulatory \nActivities (MedDRA)1 Preferred Terms (PTs)\n•PTs are not mutually exclusive\n•A single report may be assigned more than one PT\nReview of serious2 reports and medical records; categorized main diagnosis \nin a MedDRA system organ class  \nCase definitions for AESIs: Guillain -Barré Syndrome3\n1  https://www.meddra.org/   ; 2 Based on the Code of Federal Regulations 21 CFR 600.80 ; 3Sejvar JJ, et al.  Brighton Collaboration GBS Working Group. Guillain -Barré syndrome and \nFisher syndrome: case definitions and guidelines for collection, analysis, and presentation of immunization safety data. Vacc ine. 2011 Jan 10;29(3):599 -612. doi: \n10.1016/j.vaccine.2010.06.003. Epub 2010 Jun 18. PMID: 206004918\nMethods – 2: PCV20\nReporting rates\n•Use of doses distributed of PCV20 in the United States during 2022 a nd\n2023 (20,\n579,720 doses)\nEmpirical Bayesian data mining (FDA)*\n•Used to detect disproportional reporting for the entire post marketing\npe\nriod for each product\n•Identifies adverse events reported more frequently than expected afterv\naccine of interest compared with other vaccines in the VAERS database\n•Analysis by age groups and se rious reports.**\n9*The presence of disproportionality may not  suggest a safety signal.  Conversely, the absence of disproportionality does not  confirm the absence of a safety signal\nnor negate a signal detected by other methods.\n**A Serious Adverse Event (SAE) is defined as any untoward medical occurrence that meets any of the following criteria: 1. Resul ts in death; 2. Is life -threatening;\n3.Re\nquires inpatient hospitalization or prolongation of existing hospitalization; 4. Results in persistent or significant disab ility/incapacity; 5. Is a congenital \nanomaly/birth defect. [FDA regulatory definition; U.S. Code of Federal Regulations, 21 CFR 600.80. Postmarketing reporting of adverse experiences (2014).\nAvailable at: http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/cfrsearch.cfm?fr=600.80 ]\nPCV20 reports to VAERS, October 2021 –December 2023\n19 – 64 years ≥ 65 years ≥ 19 years All2\nCharacteristics1                      N (%) N (%) N (%) N (%)\nTotal reports 798 1,178 1,976 2,393\nFemale 582 (72.9) 846 (71.8) 1,428 (72.3) 1,598 (66.7)\nMale 212 (26.6) 330 (28.0) 542 (27.4) 680 (28.4)\nUnknown sex 4 (0.5) 1 (0.1) 5 (0.3) 115 (4.8)\nSerious reports349 (6.1) 70 (5.9) 119 (6) 149 (6.2)\nDeaths 2 (0.3) 9 (0.8) 11 (0.6) 20 (0.8)\nMedian age [IQR] in years 54 [45,60] 69 [66,75] 65 [56,70]\nMedian onset interval [IQR] in days 1 [0,2] 1 [0,2] 1 [0,2] 1 [0,1]\nReceived PCV20 alone 438 (54.9) 711 (60.4) 1,149 (58.1) 1,412 (59.0)\n3 Based on the Code of Federal Regulations if one of the following is reported: death, life -threatening illness, hospitalization o r prolongation of hospitalization \n                    or permanent disability 101 U.S. primary reports (foreign reports excluded) ; 2Includes reports in adults aged ≥19 years and 176 reports in persons aged 0 -18 years and 241 reports of unknown age\nMost common signs and symptoms1 in reports to VAERS following \nPCV20 in adults aged 19 –64 years, October 2021– December 2023\nPCV20  Non- serious (N=749) N (%) \nInjection site reaction 227 (30)\nPain 129 (17)\nErythema 117 (16)\nFever 103 (14)\nPain in extremity 90 (12)\nPeripheral swelling 77 (10)\nHeadache 59 (8)\nSkin warm 59 (8)\nFatigue 56 (7)\nArthralgia 52 (7)\n1 Coded using the MedDRA  Preferred Terms;  more than one MedDRA  Preferred Term  may be assigned to a single report (i.e., not mutually exclusive) 11PCV20  Serious (N=49) N (%) \nFever 14 (29)\nDyspnea 12 (25)\nCondition aggravated 10 (20)\nCough 10 (20)\nPain 10 (20)\nNausea 9 (18)\nPain in extremity 8 (16)\nDizziness 7 (14)\nFatigue 7 (14)\nHeadache 7 (14)\nMost common signs and symptoms1 in reports to VAERS following \nPCV20 in adults aged ≥65 years, October 2021 –December 2023\nPCV20  non- serious (N=1,108) N (%) \nInjection site reaction 417 (35)\nPain 180 (15)\nPain in extremity 162 (14)\nErythema 158 (13)\nFever 135 (12)\nPeripheral swelling 103 (9)\nRash 99 (8)\nFatigue 96 (8)\nHeadache 88 (7)\nPruritus 78 (7)\n1 Coded using the MedDRA  Preferred Terms;  more than one MedDRA  Preferred Term  may be assigned to a single report (i.e., not mutually exclusive) 12PCV20 Serious (N=70) N (%)\nPain 14 (20)\nAsthenia 13 (19)\nGait disturbance 11 (16)\nGuillain Barre Syndrome 11 (16)\nDyspnea 8 (11)\nFatigue 8 (11)\nFever 8 (11)\nChest pain 7 (10)\nDeath 7 (10)\nDysphagia 7 (10)\nEmpirical Bayesian data mining (as of January 26, 2024)\nDisproportional reporting observed for:\n•PT for “Guillain -Barré Syndrome” when limited to serious reports \n(EB05=3.6)1\n•When not limited to serious reports EB05=1.87\n131 EB05 = Empirical Bayesian data mining threshold for statistical alert; alert considered if EB05 >2.0\nReports to VAERS of Guillain Barre Syndrome after PCV20 vaccination \namong adults aged ≥19 years (as of December 31, 2023)\n11 verified reports of Guillain Barré Syndrome2\n•Median age (range), years: 66 years (46 -79 y ears)3\n•Median time to onset (range), days: 14 days (0 -23)\n•4 males, 7 females\n•All verified reports met Brighton Collaboration criteria for\nG\nBS:\n–2 were Brighton level 1, 6 were level 2 and 3 were level 3\n•Other vaccines during same visit (5 of 11):\n– Two RZV (Shingrix)\n– One F luad  quadrivalent\n– One bivalent mRNA COVID - 19 (Pfizer), HD -IIV4, RSV ( Arexvy )\n– One Tdap (Boostrix)Preliminary reports of Guillain \nBarre Syndrome (N=20)\nUnder \nreview1 \n(n=4)\nExcluded \nbased upon \nchart review \n(n=5)\nVerified GBS by chart review (n=11) 1 Awaiting medical records\n2 One patient had a norovirus infection 1 -2 days before neurological symptoms\n3 No GBS reports in persons aged <19 years 14\nReporting rate for GBS after PCV20, 2022 –2023\nReporting rate: 0.5 cases per million doses distributed or 0.9 cases per \n100,000 person- years (background rate 1.72 cases per 100,000 persons -\nyears) 1\n1Gubernot D, et al. U.S.  Population- B ased background incidence rates of medical conditions for use in safety assessment of \nCO VID -19 vaccines.  V accine.  2021;  39:  3666–3677.\n15\nSummary   \nVAERS received 1,976 reports after PCV20 in adults during October 2021–\nDecember 2023\n•798 in adults aged 19– 64 years; 93.9% non- serious \n•1,178 in adults aged ≥65 years; 94.1% non- serious\nMost commonly reported adverse events were injection site (e.g. injection site erythema) and systemic reactions (e.g. fever, headache); consistent \nwith findings from pre -licensure studies\n16\nSummary (continued)   \nDisproportionate reporting for Guillain -Barré Syndrome (GBS) identified in \nVAERS after PCV20 vaccine (11 verified GBS cases in adults) \nPotential safety signals detected in VAERS need to be evaluated in more robust \npopulation -based active systems such as the Vaccine Safety Datalink (VSD) or \nCenter for Medicaid Services (CMS)\n \nSeparate studies currently in progress in the VSD (CDC) and CMS (FDA) to assess PCV20 vaccine safety \nCDC and FDA will continue to closely monitor the safety of PCV20 \n17\nAcknowledgements\nCDC Immunization Safety Office\n•VAERS Team\n•Clinical Immunization Safety Assessment (CISA) Project\nFood and Drug Administration\n•Office of Biostatistics and Pharmacovigilance, Center for Biologics Evaluation\nan\nd Research\nButantan  In stitute, Sao Paulo, Brazil\n18\nFor more information, contact CDC\n1-800- CDC- INFO (232 -4636)\nTTY:  1 -888- 232- 6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.\nPhoto credit: James Gathany \n(https://wwwn.cdc.gov/phil/\nDetails.aspx?pid=8876)", "summary": "National Center for Emerging and Zoonotic Infectious Diseases Post -licensure safety surveillance of 20 -valent  pneumococcal conjugate vaccine (PCV20)  among U.S. adults in the Vaccine Adverse  Event Reporting System (VAERS) Pedro L. Moro, MD, MPH Immunization Safety Office Division of Healthcare Quality Promotion Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) February 29, 2024 Disclaimer The findings and conclusions in this presentation…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-28-29-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-02-28-29/05-Pneumococcal-Moro-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 19}
{"title": "05 Pneumococcal Forshee 508", "content": "FDA CBER: \nSafety Assessment of 20- valent Pneumococcal Conjugate \nVaccine (PCV20)\nACIP February 2024\nRichard Forshee, PhD\nOffice of Biostatistics and Pharmacovigilance\nCenter for Biologics Evaluation and Research\nUS Food and Drug Administration\n2\nDisclaimer\n•The BEST Initiative and its studies are funded by the U.S. \nFood and Drug Administration (FDA)\n•There are no potentially conflicting relationships to disclose\n•The findings and conclusions in this presentation are those of the authors and do not necessarily represent the official position of FDA, the Centers for Medicare & Medicaid Services, or Acumen, LLC\n3\n•Acute Myocardial Infarction\n•Myocarditis/Pericarditis\n•Anaphylaxis\n•Atrial Fibrillation\n•Bell’s Palsy\n•Cardiomyopathy; Heart Failure \n•Cellulitis and Infection\n•Cholecystitis or Cholelithiasis\n•Guillain -Barré syndrome\n•Immune Thrombocytopenia\n•Thrombocytopenia\n•Transient Ischemic AttackIs there an elevated risk for the listed health outcomes* \nfollowing PCV20 vaccination?\n* The list of health outcomes were identified via literature review\n4\nNear Real -Time Monitoring: Medicare Fee -for-Service (FFS) \nPopulation (Age ≥ 65 years)\nDesignConcurrent Comparator Cohort Design1 for Near Real -Time Sequential Analysis\nSelf-controlled case series planned to verify detected signals\nData Sources Centers for Medicare & Medicaid Services (CMS) – Shared Systems Data (SSD)\nStudy  PopulationMedicare FFS beneficiaries (age ≥ 65 years) receiving one dose of PCV 15 or PCV 20 \non or after the licensing date for the product-Two product populations analyzed separately\nStudy PeriodLicensing date (PCV 15 = July 16, 2021 and PCV 20 = July 1, 2021) through the end of \neach calendar month (most recent update through November 30, 2023)\nHealth OutcomesThe 12 pre-specified health outcomes identified by claims algorithms and monitored \nwithin the follow -up window for each vaccinated beneficiary\n1. Klein, N.P ., et al., Surveillance for Adverse Events After COVID -19 mRNA Vaccination. JAMA, 2021. 326(14): p. 1390- 1399.\n5\nNear Real -Time Monitoring: Medicare Fee -for-Service (FFS) \nPopulation (Age ≥ 65 years)\nStatistical \nAnalyses•Descriptive and Sequential analyses were performed monthly\n•Bayesian Poisson Regression was used to estimate the posterior distribution of incidence rate ratio (IRR) between pre-specified post -vaccination risk and comparison \nwindows for each outcome\n•Age, Sex, Immunocompromised Conditions*, Concomitant Influenza Vaccination**, and Months Post -Surveillance Start Date were included as \nadjustment covariates\n•Adjustment for claims delay was made\n•Safety signal was assessed by evaluating if:\n•The 95% Credible Interval (CI) exceeds 1 –Weak Signal\n•The 98% Credible Interval (CI) exceeds 1 – Strong Signal\n* Immunocompromised conditions was identified using administrative codes indicating presence of immunocompromising conditions  or use of immunosuppressive therapies2\n** Concomitant influenza vaccination is defined as seasonal influenza vaccination events that happened on or within 42 days prio r to PCV 20 vaccination date\n2. Greenberg JA, et al., Validation of a Method to Identify Immunocompromised Patients with Severe Sepsis in Administrative Data bases. Ann Am Thorac  Soc. 2016;13(2):253- 258.\n6\nUptake of PCV15 or PCV20 Vaccines in the Medicare FFS 65+ \nyears Population; Monthly (top) and Cumulative (bottom) Counts*\n* Data cut: 11/30/2023Total PCV 15 uptake:    53,018\nTotal PCV 20 Uptake: 2,832,555\n7\nDescriptive Characteristics of PCV 20 Vaccinees (N = 2,832,555)\nBeneficiary Characteristics Number of \nVaccinees% of \nVaccinees\nRace/Ethnicity\n Asian 70,416 2.49%\n Black 155,878 5.50%\n Hispanic 41,611 1.47%\n Alaska Native/American Indian 6,964 0.25%\n White 2,410,290 85.09%\n Other 57,163 2.02%\n Missing/Unknown 90,233 3.19%\nAge (years)\n 65-69 1,242,140 43.85%\n 70-74 599,077 21.15%\n 75-79 461,978 16.31%\n 80-84 291,753 10.30%\n 85-89 154,499 5.45%\n 90-94 64,176 2.27%\n 95+ 18,932 0.67%Beneficiary Characteristics Number of \nVaccinees% of \nVaccinees\nSex\n Female 1,614,235 56.99%\n Male 1,218,320 43.01%\nUrban/Rural\n Urban 2,375,807 83.88%\n Rural 455,787 16.09%\n Missing/Unknown 961 0.03%\nImmunocompromised Status\n Yes 144,510 5.10%\n No 2,688,045 94.90%\nMedicare -Medicaid Dual Eligibility Status**\n Yes 264,266 9.33%\n No 2,568,289 90.67%\nConcomitant Influenza Vaccination***\n Yes 496,007 17.51%\n No 2,336,548 82.49%\n* Data cut: 11/30/2023\n** Medicare- Medicaid dual eligibility status is defined as ever being dual eligible within the 3 months prior to the vaccination  date\n*** Concomitant influenza vaccination is defined as seasonal influenza vaccination events that happened on or within 42 days prior to PCV 20 vaccination date\n8\nOutcome Count and Incidence Rate (IR) among PCV20 vaccinated population*\nHealth Outcome Risk \nWindow** \n(days)Comparison \nWindow \n(days)Total\nN (IR***)Risk Window\nN (IR****)Comparison \nWindow\nN (IR****)\nAcute Myocardial Infraction 1-28 29-56 3,274 (970) 1,699 (965) 1,575 (975)\nMyocarditis/Pericarditis 1-21 22-42 80 (31) 43 (32) 37 (29)\nAnaphylaxis 0-1 3-16 25 (20) - (26) - (20)\nAtrial Fibrillation 1-42 43-84 17,925 (3,879) 9,709 (3,908) 8,216 (3,845)\nBell’s Palsy 1-42 43-84 1,090 (207) 624 (220) 466 (191)\nCardiomyopathy; Heart \nFailure1-42 43-84 16,263 (3,503) 8,778 (3,518) 7,485 (3,486)\nCellulitis and Infection 1-7 8-14 3,187 (3,548) 1,660 (3,685) 1,527 (3,410)\nCholecystitis or Cholelithiasis 1-28 29-56 665 (195) 323 (182) 342 (210)\nGuillain -Barré Syndrome 1-42 43-84 29 (6) - (8) - (4)\nImmune Thrombocytopenia 1-42 43-84 49 (10) 30 (11) 19 (8)\nThrombocytopenia 1-28 29-56 3,552 (1,053) 1,787 (1,015) 1,765 (1,093)\nTransient Ischemic Attack 1-28 29-56 621 (182) 318 (179) 303 (186)\n* Data cut: 11/30/2023, # of PCV 20 total uptake: 2,832,555\n** Risk and comparison windows are defined as the number of days post vaccination *** All IRs expressed as IR per 100,000 person -years\n**** For the health outcome that has risk or comparison windows count less than 11, the counts for both windows are masked by  “-”\n9\nIRR between Risk and Comparison Windows with 95% and 98% CI among \nPCV20 Vaccinated Population*\nHealth Outcome IRR** 95% CI 98% CI\nAcute Myocardial Infraction 0.95 (0.89, 1.02) (0.87, 1.03)\nMyocarditis/Pericarditis 1.05 (0.69, 1.64) (0.64, 1.77)\nAnaphylaxis 1.11 (0.31, 3.12) (0.22, 3.78)\nAtrial Fibrillation 0.98 (0.95, 1.01) (0.95, 1.02)\nBell’s Palsy 1.13 (1.00, 1.29) (0.97, 1.32)\nCardiomyopathy; Heart Failure 0.96 (0.93, 0.99) (0.92, 1.00)\nCellulitis and Infection 1.06 (0.99, 1.14) (0.97, 1.15)\nCholecystitis or Cholelithiasis 0.85 (0.73, 1.00) (0.71, 1.03)\nGuillain -Barré Syndrome 2.19 (0.97, 5.42) (0.82, 6.50)\nImmune Thrombocytopenia 1.35 (0.75, 2.50) (0.67, 2.78)\nThrombocytopenia 0.89 (0.83, 0.95) (0.82, 0.97)\nTransient Ischemic Attack 0.94 (0.80, 1.11) (0.78, 1.14)\n* Data cut: 11/30/2023, # of PCV 20 total uptake: 2,832,555** IRR = Incidence rate ratioNo statistically \nsignificant elevated \nrisk was detected\n10\nEstimated Posterior Distributions of IRR from Sequential Analyses at \nDifferent Data Cuts – Myocarditis/Pericarditis\nMedian of the Posterior Distribution \n(IRR = 1.05)\nIRR = 1, meaning no rate difference \nin the health outcome between risk and comparison windows\nIRR posterior distribution from Bayesian model using data through November 2023\n11\nEstimated Posterior Distributions of IRR from Sequential \nAnalyses at Different Data Cuts – All  Health Outcomes\n\n12\nSummary \n•Incidence rates post PCV 20\n•Incidence rates for Myocarditis/Pericarditis, Anaphylaxis, Guillain -Barré \nSyndrome and Immune Thrombocytopenia are less than  100 cases per 100,000 \nperson -years\n•Signal detection\n•The estimated IRRs and CIs did not identify statistically significant risk \nelevation following PCV 20 vaccination for any of the outcomes (no significant \nevidence that IRR > 1)\n•We continue to monitor and evaluate the health outcomes\nNote: Summary based on results from data cut: 11/30/2023\n13\nLimitations for Sequential Monitoring  \n•Statistically significant results may appear and disappear from \nmonth to month due to use of Bayesian methods.\n•Events were not chart- confirmed and the Positive Predictive \nValue (PPV) for some outcomes are likely low, e.g. The PPV for \nBell’s Palsy was 12.66% and the PPV for ITP was 4.00% in a \nrecent study.\n•Residual confounding may still exist given the limited number \nof variables being adjusted in the regression model\n•Large uncertainty of incidence rate ratios for certain outcomes\n•Small number of events, wide credible intervals \n14\nFuture Planning  \n•Active monitoring to continue monthly\n•End of surveillance analysis may be performed using the self- controlled \ncase series (SCCS) method for each outcome where there is sufficient \nsample size for a powered analysis\n15\nSummary of Evidence\n•No GBS signal in clinical trials\n•GBS signal for PCV20 in VAERS\n•Currently no GBS signal in Medicare sequential \nmonitoring. Monitoring is ongoing.\n•Significant uncertainty because of the small number of cases observed\n•Limitations in VAERS and Medicare studies\n16\nAcknowledgements\nFDA CBER\nXinyi Ng\nRichard ForsheeWhitney SteeleBarbee Whitaker\nwww.bestinitiative.orgAcumenYue WuMao HuJing WangNatalie SistoYoganand ChillarigeBing LyuJianfeng ZhuangPurva ShahWenxuan ZhouHolin ChenSamikshya SiwakotiYenlin LaiCenters for Medicare \nand Medicaid Services (CMS)", "summary": "FDA CBER:  Safety Assessment of 20- valent Pneumococcal Conjugate  Vaccine (PCV20) ACIP February 2024 Richard Forshee, PhD Office of Biostatistics and Pharmacovigilance Center for Biologics Evaluation and Research US Food and Drug Administration 2 Disclaimer •The BEST Initiative and its studies are funded by the U.S.  Food and Drug Administration (FDA) •There are no potentially conflicting relationships to disclose •The findings and conclusions in this presentation are those of the authors and…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-28-29-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-02-28-29/05-Pneumococcal-Forshee-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 16}
{"title": "06 Pneumococcal Kobayashi 508", "content": "Centers for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nPreliminary Work Group Interpretations of EtR  and \nNext Steps\nFebruary 2024, ACIP Meeting\nFebruary 29, 2024\nMiwako Kobayashi, MD, MPH, FACP , FIDSA\n1.Should PCV21 be recommended for U.S. adults aged ≥19 years who  \ncurrently have a recommendation to receive a PCV*? \nComparison (current recommendations):\nAdults aged ≥19 years  who have not received a PCV\nOne dose of PCV15 followed by PPSV23\nOne dose of PCV20\nAdults aged ≥19 years who have received a PCV but have not completed the recommended series\nOne dose of PCV20\n≥1 dose of PPSV23Policy Questions Being Considered by the Work Group \n*Includes,\n• Adults aged ≥65 years who have never received a PCV\n• U.S. adults aged 19-64 years with a risk condition, who have never received a PCV\n• U.S. adults aged ≥19 year who have received a PCV (i.e., PCV7, PCV13, or PCV15), but have not completed the recommended series\n2. Should PCV21 be recommended for U.S. adults aged 50- 64 years who \ncurrently do not have a risk -based pneumococcal vaccine indication?\n3. Should PCV21 be recommended for U.S. adults aged 19 -49 years who \ncurrently do not have a risk -based pneumococcal vaccine indication?\nComparison (current recommendation):\nNo vaccine\nQuestions 2 and 3 imply a new age -based recommendation for these age groups.Policy Questions Being Considered by the Work Group \nEtR  Domain Question\nPublic Health Problem •Is the problem of public health importance?\nBenefits and Harms •How substantial are the desirable anticipated effects?\n•How substantial are the undesirable anticipated effects?\n•Do the desirable effects outweigh the undesirable effects?\n•What is the overall certainty of this evidence for the critical outcomes?\nValues •Does the target population feel the desirable effects are large relative to \nthe undesirable effects?\n•Is there important variability in how patients value the outcomes?\nAcceptability •Is the intervention acceptable to key stakeholders?\nFeasibility •Is the intervention feasible to implement?\nResource Use •Is the intervention a reasonable and efficient allocation of resources?\nEquity •What would be the impact of the intervention on health equity?Evidence to Recommendations ( EtR ) framework\n4\nEtR  Domain Question\nPublic Health Problem •Is the problem of public health importance?\nBenefits and Harms •How substantial are the desirable anticipated effects?\n•How substantial are the undesirable anticipated effects?\n•Do the desirable effects outweigh the undesirable effects?\n•What is the overall certainty of this evidence for the critical outcomes?\nValues •Does the target population feel the desirable effects are large relative to \nthe undesirable effects?\n•Is there important variability in how patients value the outcomes?\nAcceptability •Is the intervention acceptable to key stakeholders?\nFeasibility •Is the intervention feasible to implement?\nResource Use •Is the intervention a reasonable and efficient allocation of resources?\nEquity•What would be the impact of the intervention on health equity?Evidence to Recommendations ( EtR ) framework\n5\nEtR  Public Health Problem\nIs pneumococcal disease of public health importance? \nPrior to the COVID-19 pandemic, estimated to have caused \nevery year1:\n–≥100,000 non- invasive pneumococcal pneumonia hospitalizations\n–≥30,000 invasive pneumococcal disease (IPD) cases (e.g., bacteremic pneumonia, \npneumococcal bacteremia, meningitis)\n•3,000 IPD deaths\nRisk of disease and severe outcomes is higher among older adults and adults with certain risk conditions.\n–Over one -third of adults aged ≥65 years hospitalized with community -acquired \npneumonia in Louisville, KY died within 1 year2\n–>80% of IPD cases occurred among adults with risk -based indications3Pneumococcal Disease Burden among U.S. Adults\n1. Kobayashi M. October 20, 2021 ACIP Meeting Presentation. Considerations for Age -Based and Risk -Based Use of PCV15 and PCV20 amon g U.S. Adults and Proposed Policy Options. \n2. Older Adults Hospitalized for Pneumonia in the United States: Incidence, Epidemiology, and Outcomes - Arnold - 2020 - Journal of  the American Geriatrics Society - Wiley Online Library\n3. CDC Active Bacterial Core surveillance unpublished data\nIPD incidence reached a historically low level early in the COVID -19 \npandemic, but increasing toward pre- COVID levels\nIPD=invasive pneumococcal disease; 2022 data in gray are preliminary\nABCs Bact  Facts Interactive Data Dashboard | CDC\n\nNew pneumococcal conjugate vaccines, PCV15 and PCV20, \nwere recommended for adults and children in recent years\n2021 2023 2022\nPCV15 : ChildrenPCV20 : Expanded \nindication for adults  \nwho previously \nreceived PCV13\nPCV20 : ChildrenPCV15 and PCV20:  Adults \nwho have not received \nPCV or whose vaccination history is unknown\n30–40% of adult IPD cases* are caused by serotypes not \ncontained in currently available vaccines; PCV21 contains \nmost  of them.\n*Based on ABCs 2018 –2022 data421615216\n0102030405060708090100Percent IPD\nPCV15+6C PCV20/non-PCV15\nPPV23/non-PCV20 PCV21/non-PPV23\nNVT42129298\n0102030405060708090100Percent IPD\nPCV15+6C PCV20/ non-PCV15\nPPV23/ non-PCV20 PCV21/ non-PPV23\nNVTAged 19 –64 years, with a risk- based \nindication Aged ≥65 years\n1. In adults currently recommended to receive a PCV ? (group 1)Is pneumococcal disease of public health importance?\n□ No \n□ Probably no  \n□ Probably yes \n□ Yes \n□ Varies  \n□ Don’t know   Minority opinion (probably yes):\n•Pneumococcal disease burden has decreased from \nbefore \n•Increase in disease incidence in recent years does not mean the incidence will continue to increase (i.e., may stabilize at pre -COVID -19 levels) \n2. In adults aged 50– 64 years who currently do not have a risk -based \npneumococcal vaccine indication ? (group 2)Is pneumococcal disease of public health importance?\n□ No \n□ Probably no  \n□ Probably yes \n□ Yes \n□ Varies  \n□ Don’t know   •Disease incidence in this age group overall is lower \ncompared with adults aged ≥65 years (IPD incidence ~23% lower)\n3. In adults aged 19 –49 years who currently do not have a risk -based \npneumococcal vaccine indication ? (group 3)Is pneumococcal disease of public health importance?\n□ No \n□ Probably no  \n□ Probably yes \n□ Yes \n□ Varies  \n□ Don’t know   •The most common WG member responses were \n“No”(19%), “Probably No”(31%), and “Don’t know (25%)\n•Adults aged 19 –49 years have even lower disease \nincidence compared with adults aged 50 –64 years\nEtR  Benefits and Harms\n1. How substantial are the desirable  anticipated effects of PCV21 vaccination?\n2. How substantial are the undesirable  anticipated effects of PCV21 \nvaccination?\n3. Do the desirable effects of PCV21 vaccination outweigh the undesirable \neffects?\n4. What is the overall certainty of this evidence for the critical outcomes? \nOutcomes (Benefits)\n*Rated on a 1 to 9 scale, where 7 –9 are critical, 4 –6 are important, 1 –3 are of limited importance\nGMT= geometric mean titers; OPA=opsonophagocytic activity\nSee supplementary slides for details of methodsOutcome Importance* Description\nVT- IPD Critical\nVT- non- bacteremic  \npneumococcal pneumoniaCritical\nVT- pneumococcal deaths Critical\nAll IPD Important\nNon -bacteremic \npneumococcal pneumoniaImportant\nAll-cause death ImportantStudies assessing PCV21 against these \nclinical outcomes are currently not \navailable\nPCV21 immunogenicity studies\n•OPA GMT\n•≥4-fold rise in serotype -specific \nOPA responses\nOutcomes (Harms)\n*Rated on a 1 to 9 scale, where 7 –9 are critical, 4 –6 are important, 1 –3 are of limited importance\nSee supplementary slides for details of methodsOutcome Importance* Description \nSerious adverse events \n(SAE)Critical Safety data for PCV21 are available.\nLast name first \nauthor, Publication \nyearStudy design Country Age Total population N Intervention N comparison OutcomesFunding \nsource\nPlatt, Lancet ID \n2023RCT (Phase II) U.S. Adults ≥50 years 508 254 PPSV23: 254Immunogenicity and \nSafetyMERCK\nV116 -003RCT (Phase III); \npivotal studyU.S., Australia, Belgium, \nChile, Germany, Korea, \nNew Zealand, Puerto \nRico, Sweden, Taiwan, \nTurkeyHealthy adults ≥50 years, \npneumococcal vaccine – \nnaïve2,6631179 PCV20: 1,177\nImmunogenicity and \nSafetyMERCKHealthy adults 18 - 49 years, \npneumococcal vaccine – \nnaïve200 PCV20:  100\nV116 -005RCT (Phase III)U.S. Adults ≥50 years 1,080(V116 + QIV, \ncoadministered): 536(QIV followed by \nV116) : 536Immunogenicity and\nSafetyMERCK\nV116 -006RCT (Phase III)U.S., Canada, Israel, \nFrance, Italy, Japan, \nKorea, Spain, TaiwanAdults ≥50 years, previous \nPPSV23 ≥1 year prior to \nenrollment348 229PCV15, n=119\nImmunogenicity\nand\nSafetyMERCKAdults ≥50 years, previous \nPCV13 ≥1 year prior to \nenrollment259 174PPSV23\nN=85\nAdults ≥50 years, \nPCV13+PPSV23, \nPCV15+PPSV23, PCV15, \nPCV20, or PPSV23+PCV13 ≥1 \nyear prior to enrollment105 105 None\nV116 -007 RCT (Phase III)Belgium,  Chile,  France,  \nSouth Africa,\nThailand,\nUnited StatesAdults living with HIV,\n≥18 years; 36% prior PCV13 \nor PPSV23*313 156PCV15+PPSV23, \nn=157Immunogenicity and \nSafetyMERCK\nV116 -004RCT (Phase III)U.S., Austria, Canada, \nDenmark, Finland, Israel, \nPoland, SpainAdults 18 - 49 years with \nunderlying chronic \nconditions2,162 1,617 PPSV23:540 SafetyMERCKPCV21 Clinical Trials Included in Evidence Review\nCertainty assessment № of patients Effect\nCertainty Importance№ of \nstudiesStudy designRisk of \nbiasInconsistency Indirectness ImprecisionOther \nconsiderationsPCV21 comparisonRelative\n(95% CI)Absolute\n(95% CI)\nVT-IPD, VT -nonbacteremic pneumococcal pneumonia, VT -pneumococcal mortality outcome (Assessed with: Immunogenicity)\n51-5Randomized \nstudiesNot \nseriousNot serious SeriousaNot serious Not serious 123 - 1161 58 - 1162• PCV21 met non -inferiority criteriab \nfor 9/9 shared and superiority \ncriteriac for 12/12 unique serotypes \nvs. PPSV23\n• PCV21 met non -inferiority criteriad \nfor 10/10 shared and superiority \ncriteriae 10/11 unique serotypes vs. \nPCV20\n• PCV21 had numerically higher \nimmune responses for 1 -4/6 shared \nand all unique serotypes vs. PCV15Moderate CriticalGRADE Summary of Findings Table\n1: Adults currently recommended to receive PCV\na. These are all immunogenicity studies and there are no correlates of protection for some critical outcomes considered.\nb. Noninferiority for GMT ratio was defined as the lower bound of the 95% CI of the estimated OPA GMT ratio ({PCV21:PPSV23} to be >  0.33.\nc. Superiority for GMT ratio was defined as the lower bound of the 95% CI of the estimated OPA GMT ratio [PCV21:PPSV23] to be > 1.0.\nd. Noninferiority for GMT ratio was defined as the lower bound of the 2 sided 95% CI of the OPA GMT ratio [PCV21 / PCV20] to be >0.5.\ne. Superiority for GMT ratio was defined as the lower bound of the 2 sided 95% CI of the OPA GMT ratio [PCV21 / PCV20] to be >2. 0.\nReferences\n1. Platt H, Omole T, Cardona J, Fraser NJ, Mularski  RA, Andrews C, Daboul  N, Gallagher N, Sapre A, Li J, Polis A, Fernsler  D, Tamms G, Xu W, Murphy R, Skinner J, Joyce J, Musey L. Safety, tolerability, and immunogenicity of a 21- valent pneumococcal c onjugate vaccine, \nV116, in healthy adults: phase 1/2, randomised, double- blind, active comparator -controlled, multicentre, U.S.- based trial. Lancet Infect Dis. 2023 Feb;23(2):233- 246. doi: 10.1016/S1473- 3099(22)00526 -6. Epub 2022 Sep 15. PMID: 36116461.\n2. V116- 003. A clinical study to evaluate the safety, tolerability, and immunogenicity of V116 compared to PCV20 in pneumococcal vaccine -naïve adults\n3. V116- 006. A Phase 3 Clinical Study to Evaluate the Safety, Tolerability, and Immunogenicity of V116 in Pneumococcal Vaccine- Experienced Adults 50 Years of Age or Older \n4. V116- 007. A Phase 3, Multicenter, Randomized, Double- blind, Active Comparator - Controlled Study to Evaluate the Safety, Tolerabi lity, and Immunogenicity of V116 in Adults Living With HIV\n5. V166- 005. A clinical study comparing the immunogenicity and safety of V116 when administered concomitantly with inactivated infl uenza vaccine \nGRADE Summary of Findings Table\n1: Adults currently recommended to receive PCV\na. These are all immunogenicity studies and there are no correlates of protection for some critical outcomes considered.\nb. Noninferiority for GMT ratio was defined as the lower bound of the 95% CI of the estimated OPA GMT ratio ({PCV21:PPSV23} to be >  0.33.\nc. Superiority for GMT ratio was defined as the lower bound of the 95% CI of the estimated OPA GMT ratio [PCV21:PPSV23] to be > 1.0.\nd. Noninferiority for GMT ratio was defined as the lower bound of the 2 sided 95% CI of the OPA GMT ratio [PCV21 / PCV20] to be >0.5.\ne. Superiority for GMT ratio was defined as the lower bound of the 2 sided 95% CI of the OPA GMT ratio [PCV21 / PCV20] to be >2. 0.\n See supplementary slides for details\nCertainty assessment № of patients Effect\nCertainty Importance№ of \nstudiesStudy designRisk of \nbiasInconsistency Indirectness ImprecisionOther \nconsiderationsPCV21 comparisonRelative\n(95% CI)Absolute\n(95% CI)\nSerious adverse events following immunization\n61-6Randomized \nstudiesNot \nseriousNot serious Not serious SeriousfNot serious 57/4445\n(1.3%)63/2962\n(2.1%)Absolute % difference for SAEs across \nstudies is -0.8%; two SAEs deemed \nvaccine -relatedg in the V116 group \nreportedModerate CriticalGRADE Summary of Findings Table\n1: Adults currently recommended to receive PCV\nf. few vaccine- related serious adverse events reported. \ng. Bronchospasm (V116- 005): 50- year-old female in the sequential group with bronchospasm within 30 minutes after the 2ndvaccination (V116); duration 23 hours; resolved; Injection site cellulitis (V116- 006): 67- year-old female in Cohort 1 (prior PPSV23) with i njection site cellulitis \non Day 6; duration 1.57 weeks; resolved (Merck, unpublished).\nReferences\n1. Platt H, Omole T, Cardona J, Fraser NJ, Mularski  RA, Andrews C, Daboul  N, Gallagher N, Sapre A, Li J, Polis A, Fernsler  D, Tamms G, Xu W, Murphy R, Skinner J, Joyce J, Musey L. Safety, tolerability, and immunogenicity of a 21- valent pneumococcal c onjugate vaccine, \nV116, in healthy adults: phase 1/2, randomised, double- blind, active comparator -controlled, multicentre, U.S.- based trial. Lancet Infect Dis. 2023 Feb;23(2):233- 246. doi: 10.1016/S1473- 3099(22)00526 -6. Epub 2022 Sep 15. PMID: 36116461.\n2. V116- 003. A clinical study to evaluate the safety, tolerability, and immunogenicity of V116 compared to PCV20 in pneumococcal vaccine -naïve adults\n3. V116- 006. A Phase 3 Clinical Study to Evaluate the Safety, Tolerability, and Immunogenicity of V116 in Pneumococcal Vaccine- Experienced Adults 50 Years of Age or Older \n4. V116- 007. A Phase 3, Multicenter, Randomized, Double- blind, Active Comparator - Controlled Study to Evaluate the Safety, Tolerabi lity, and Immunogenicity of V116 in Adults Living With HIV \n5. V166- 005. A clinical study comparing the immunogenicity and safety of V116 when administered concomitantly with inactivated infl uenza vaccine\n6. V116- 004. A Phase 3 Randomized, Double- blind, Active Comparator -controlled, Lot to- Lot Consistency Study to Evaluate the Safety,  Tolerability, and Immunogenicity of V116 in Adults 18 to 49 Years of Age. \nGRADE Summary of Findings Table\n1: Adults currently recommended to receive PCV\nf. few vaccine- related serious adverse events reported. \ng. Bronchospasm (V116- 005): 50- year-old female in the sequential group with bronchospasm within 30 minutes after the 2ndvaccination (V116); duration 23 hours; resolved; Injection site cellulitis (V116- 006): 67- year-old female in Cohort 1 (prior PPSV23) with i njection site cellulitis \non Day 6; duration 1.57 weeks; resolved (Merck, unpublished).\nSee supplementary slides for details\n1. How substantial are the desirable  anticipated effects of \nPCV21 vaccination?\n□ Minimal\n□ Small \n□ Moderate  \n□ Large  \n□ Varies  \n□ Don’t know   □ Minimal\n□ Small \n□ Moderate  \n□ Large  \n□ Varies  \n□ Don’t know   □ Minimal\n□ Small \n□ Moderate  \n□ Large  \n□ Varies  \n□ Don’t know   1. Adults currently \nrecommended to receive PCV2. Adults aged 50 –64 years with \nno risk -based indication3. Adults aged 19 –49 years with \nno risk -based indication\n 1. Adults currently recommended to receive PCV\n 2. Adults aged 50 –64 years with no risk- based indication\n 3. Adults aged 19 –49 years with no risk- based indication2. How substantial are the un desirable  anticipated effects \nof PCV21 vaccination?\n□ Minimal\n□ Small \n□ Moderate  \n□ Large  \n□ Varies  \n□ Don’t know   \n□ Favors PCV21 use\n□ Favors current \n□ Favors both  \n□ Favors neither  \n□ Varies  \n□ Don’t know   3. Do the desirable effects of PCV21 vaccination outweigh \nthe undesirable  anticipated effects?\n1. Adults currently \nrecommended to receive PCV2. Adults aged 50 –64 years with \nno risk -based indication3. Adults aged 19 –49 years with \nno risk -based indication\n□ Favors PCV21 use\n□ Favors current (no \nvaccine) \n□ Favors both  \n□ Favors neither  \n□ Varies  \n□ Don’t know   □ Favors PCV21 use\n□ Favors current (no \nvaccine) □ Favors both  \n□ Favors neither  \n□ Varies  \n□ Don’t know   \n•None selected by the majority\n•“Favors current” and “favors PCV21 \nuse” were the most common responses selected by similar number of members\nBased on available data, no concerns about the risks outweighing the \nbenefits of PCV21 vaccination\nFor adults who currently have a PCV recommendation, PCV21 provides broader serotype coverage than currently recommended vaccinesSummary of Work Group Discussions:\nComments in favor of PCV21 use\nWe can expect a more robust immune response from administering \nPCV21 at age 50 –64 years (vs. age ≥65 years) and before a portion of that \npopulation develops an immunocompromising condition  Summary of Work Group Discussions:\nIn favor of lowering the age -based recommendation (question 2)\nThe degree of benefits for adults who currently don’t have vaccine \nrecommendations is uncertain\nEpidemiology does not support expanding the vaccine indications to younger adults without a risk -based indication\nYounger adults (early 20s) would have received a PCV as a child\nWe could miss the opportunity to provide protection against disease later in life if we lowered the age- based recommendation\n–Limited data on duration of protection or protection against disease from multiple \nPCV doses in adults\nNeed to review cost- effectiveness analysis dataSummary of Work Group Discussions:\nConcerns/uncertainties of lowering the age- based recommendation \n(especially question 3)\nEtR : Equity\nWhat would be the impact of recommending PCV21 use for adults on \nhealth equity? \nRacial disparities in IPD incidence exist\nWhite non- Hispanic adults tend to have \nhighest vaccine coverage1 compared with \nother race/ethnicity groups\nRemaining disparities in IPD incidence are \nprimarily due to non- PCV13 -type  diseaseRacial disparities exist in IPD incidence and vaccine \ncoverage\nFigure: ABCs unpublished data\n1. Vaccination Coverage among Adults in the United States, National Health Interview Survey, 2021 | CDC\n\nAdults experiencing homelessness (especially Western United States)\n•100– 300 times higher serotype 4  IPD incidence reported in people experiencing \nhomelessness (PEH) vs. non -PEH in the Western United States1\nAdults in Alaska (especially Alaska Native adults)\n•88-fold increase in serotype 4 IPD incidence reported in adults in Alaska, 2011 –2018 \nvs. 2019– 20202 Increase in serotype 4  (included in currently available vaccines, \nnot in PCV21) IPD reported in certain subpopulations\n1. Upsurge of Conjugate Vaccine Serotype 4 Invasive Pneumococcal Disease Clusters Among Adults Experiencing Homelessness in C alifornia, Colorado, and New Mexico | The \nJournal of Infectious Diseases | Oxford Academic (oup.com)\n2. Invasive Pneumococcal Disease and Potential Impact of Pneumococcal Conjugate Vaccines Among Adults, Including Persons Experie ncing Homelessness— Alaska, 2011 –2020 | \nClinical Infectious Diseases | Oxford Academic (oup.com)\n1. In adults currently recommended to receive a PCV ?What would be the impact of recommending PCV21 use for \nadults on health equity? \n□ Reduced\n□ Probably reduced \n□ Probably no impact  \n□ Probably increased\n□ Increased  \n□ Varies \n□ Don’t know •Additional serotype coverage by PCV21 is expected \nto reduce racial disparities in remaining \npneumococcal disease burden. \n•For adults who have already received a PCV, \nrecommending a second PCV dose to complete \nseries might magnify the underlying disparities in \nvaccine coverage.  \n2. In adults aged 50– 64 years who currently do not have a risk -based pneumococcal \nvaccine indication ?\n3. In adults aged 19 –49 years who currently do not have a risk -based pneumococcal \nvaccine indication ?What would be the impact of recommending PCV21 use for \nadults on health equity? \n□ Reduced\n□ Probably reduced \n□ Probably no impact  \n□ Probably increased\n□ Increased  \n□ Varies \n□ Don’t know •Probably more equitable to lower the age threshold \nfor the age -based recommendation, which may \nimprove vaccine coverage in those who currently have risk -based indications\nEtR Domains 1. Adults with current PCV \nrecommendations2. Adults aged 50– 64 \nyears, no risk -based \nindication3. Adults aged 19– 49 \nyears, no risk -based \nindication\nPublic Health Problem Yes Probably Yes No/Probably No\nBenefits and Harms\na. Benefits Moderate/Large Small/Moderate Minimal/Small\nb. Harms Minimal\nc. Benefit>Harm? Favors PCV21 use Favors PCV21/Favors no \nvaccine (split)\nd. Overall certainty: effectiveness Moderate\ne. Overall certainty: safety Moderate\nEquity Probably increasedSummary of Work Group Interpretation of the EtR  Domains \nWork Group Next Steps\nReview findings from cost -effectiveness analyses \nReview evidence and discuss interpretations of remaining EtR \ndomains (Values, Acceptability, Resource Use, Feasibility)\nDraft policy options on PCV21 use in U.S. adults for \nconsideration by the committee\n–Including considerations for expanding the current risk -based vaccine \nindications to include adults with chronic kidney disease (CKD) who are not on \nmaintenance dialysisWork Group Next Steps \nConsiderations for including earlier stages of \nCKD for risk -based pneumococcal vaccine \nindications\nIndications for risk -based pneumococcal vaccine recommendations Children Adults\nAlcoholism\nChronic heart disease†\nChronic kidney disease (excluding maintenance dialysis and nephrotic syndrome)Chronic liver disease\nChronic lung disease \nCigarette smokingDiabetes mellitusCerebrospinal fluid leakCochlear implant\nMaintenance dialysis or nephrotic syndrome\nCongenital or acquired asplenia, or splenic dysfunctionCongenital or acquired immunodeficiency\n¶\nDiseases and conditions treated with immunosuppressive drugs or radiation therapy**HIV infectionSickle cell disease or other hemoglobinopathies\nSolid organ transplantRisk -based pneumococcal vaccine indication was expanded to \ninclude earlier -stage CKD (i.e., those not on dialysis) in children. \nDoes evidence support the change in adults as well? \nIn favor of expanding indications in \nadults:\nPneumococcal disease risk is increased in earlier CKD stages\nAllows adults to receive vaccine when immune response is more robust Concerned/cautious about expanding indications in adults\nUnlike children, CKD is more common in adults\nInclusion of earlier stages, such as CKD stage 3a, could potentially result in expanding the risk- based indication to \na much larger proportion of adults (unless they already have other risk-based indications)\nWould like to see a cost -benefit \nanalysis Summary of Work Group Discussion to Date\nConsidering:\nAdditional pneumococcal vaccines for adults are currently under investigation and \nmay be approved in the near future, and  \nDynamic changes in pneumococcal disease incidence are anticipated post -COVID -19 \nand with increased uptake in PCV15/PCV20 in children and adults\n \n1. Do you have any feedback on the policy questions being considered by the WG?2. What additional data would be helpful to inform the discussions on PCV21 use in \nadults?\nIn addition,\n3. What additional data would be needed to help inform the discussions on expanding \nthe risk- based indications to include adults with CKD? \n Questions for the Committee\nACIP and the Pneumococcal Vaccines Work Group\nCDC contributors and consultants: Ryan Gierke, Jennifer Farrar, Kristin Andrejko, \nLindsay Zielinski, Emma Accorsi, Wei Xing, Adam Cohen, Alison Albert, Angela Jiles, Noele Nelson, Kimberly Fox, Pedro Moro, Elizabeth Velazquez, Janelle King, Fangjun Zhou, Marc Fischer, Cheryl Ward, Rebecca Morgan, Doug Campos -Outcalt\nActive Bacterial Core surveillance sites and programAcknowledgments\nFor more information, contact CDC\n1-800- CDC- INFO (232 -4636)\nTTY:  1 -888 -232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention.\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nThank you!\nGRADE Evidence Summary \nSupplemental Slides\nPICO 1: Adults currently recommended to receive PCV\nPolicy question: Should PCV21 be recommended for U.S. adults aged ≥19 years who currently have a \nrecommendation to receive a pneumococcal conjugate vaccine?\nPopulation •U.S. adults aged ≥65 years who have never received a PCV\n•U.S. adults aged 19 –64 years with a risk condition, who have never received a PCV\n•U.S. adults aged ≥19 years who have received a PCV (i.e., PCV7, PCV13, or PCV15), but \nhave not completed the recommended series\nIntervention One dose of PCV21 (V116)\nComparison Adults who have not received a PCV\n•One dose of PCV15 followed by PPSV23\n•One dose of PCV20\nAdults who have received a PCV but have not completed the recommended series\n•One dose of PCV20\n•≥1 dose of PPSV23\nOutcomes Vaccine type (VT)-IPD, VT -non -bacteremic  pneumococcal , VT -pneumococcal mortality, \nserious adverse events\nPICO2: Adults aged 50–64 years, no risk- based indications\nPolicy question: Should PCV21 be recommended for U.S. adults aged 50 –64 years who currently \ndo not have a risk -based pneumococcal vaccine indication?  \nPopulation U.S. adults aged 50 –64 years who currently do not have a risk -based pneumococcal \nvaccine indication\nIntervention One dose of PCV21\nComparison No vaccination\nOutcomes Vaccine type (VT) -IPD, VT -non- bacteremic pneumococcal , VT -pneumococcal \nmortality, serious adverse events\nPICO3: Adults aged 19–49 years, no risk- based indications\nPolicy question: Should PCV21 be recommended for U.S. adults aged 19 –49 years who currently \ndo not have a risk -based pneumococcal vaccine indication?  \nPopulation U.S. adults aged 19 –49 years who currently do not have a risk -based pneumococcal \nvaccine indication\nIntervention One dose of PCV21\nComparison No vaccination\nOutcomes Vaccine type (VT) -IPD, VT -non- bacteremic pneumococcal , VT -pneumococcal \nmortality, serious adverse events\nSearch strategy\nDatabase StrategyNo. \nidentifiedIncluded in \nGRADE\nclinicaltrials\n.govSearch terms (searched separately): \"V116\"; \"21 -valent pneumococcal conjugate vaccine\";\"PCV21\"\nInclusion: Relevant Phase 2 or 3 randomized controlled trials of PCV21\n• Involved human subjects\n• Reported primary data\n• Included adults (age ≥19 years)\n• Included data relevant to the efficacy or effectiveness or immunogenicity and safety outcomes \nbeing measured\n10 6\nPubmed \"V116\" or \"21 -valent pneumococcal conjugate vaccine\" or \"PCV21\" \nIncluded studies using the criteria listed above25 1\nAdditional \nresourcesUnpublished and other relevant data by consulting with vaccine manufacturers and subject matter experts\n5\nEvidence Retrieval\nClinicaltrials.gov\nN=10\n6 studies included for GRADEPubmed\nN=25\nPCV21 50 – 64y, no risk \nbased indication\nImmunogenicity (n=2)\nSAE (n=2)Unpublished data\nN=5\nPCV21 for currently \nrecommended adults\n(n=6)\nImmunogenicity (n=5)\nSAE (n=6)PCV21 19 – 49y, no risk \nbased indication\nImmunogenicity (n=1)\nSAE (n=1)\nLast name first \nauthor, Publication \nyearStudy design Country Age Total population N Intervention N comparison OutcomesFunding \nsource\nPlatt, Lancet ID \n2023RCT (Phase II) U.S. Adults ≥50 years 508 254 PPSV23: 254Immunogenicity and \nSafetyMERCK\nV116 -003RCT (Phase III); \npivotal studyU.S., Australia, Belgium, \nChile, Germany, Korea, \nNew Zealand, Puerto \nRico, Sweden, Taiwan, \nTurkeyHealthy adults ≥50 years, \npneumococcal vaccine – \nnaïve2,6631179 PCV20: 1,177\nImmunogenicity and \nSafetyMERCKHealthy adults 18 - 49 years, \npneumococcal vaccine – \nnaïve200 PCV20:  100\nV116 -005RCT (Phase III)U.S. Adults ≥50 years 1,080(V116 + QIV, \ncoadministered): 536(QIV followed by \nV116) : 536Immunogenicity and\nSafetyMERCK\nV116 -006RCT (Phase III)U.S., Canada, Israel, \nFrance, Italy, Japan, \nKorea, Spain, TaiwanAdults ≥50 years, previous \nPPSV23 ≥1 year prior to \nenrollment348 229PCV15, n=119\nImmunogenicity\nand\nSafetyMERCKAdults ≥50 years, previous \nPCV13 ≥1 year prior to \nenrollment259 174PPSV23\nN=85\nAdults ≥50 years, \nPCV13+PPSV23, \nPCV15+PPSV23, PCV15, \nPCV20, or PPSV23+PCV13 ≥1 \nyear prior to enrollment105 105 None\nV116 -007 RCT (Phase III)Belgium,  Chile,  France,  \nSouth Africa,\nThailand,\nUnited StatesAdults living with HIV,\n≥18 years; 36% prior PCV13 \nor PPSV23*313 156PCV15+PPSV23, \nn=157Immunogenicity and \nSafetyMERCK\nV116 -004RCT (Phase III)U.S., Austria, Canada, \nDenmark, Finland, Israel, \nPoland, SpainAdults 18 - 49 years with \nunderlying chronic \nconditions2,162 1,617 PPSV23:540 SafetyMERCKPCV21 Clinical Trials included in Evidence Review\nCertainty assessment № of patients Effect\nCertainty Importance№ of \nstudiesStudy designRisk of \nbiasInconsistency Indirectness ImprecisionOther \nconsiderationsPCV21 comparisonRelative\n(95% CI)Absolute\n(95% CI)\nVT-IPD, VT -nonbacteremic pneumococcal pneumonia, VT -pneumococcal mortality outcome (Assessed with: Immunogenicity)\n51-5Randomized \nstudiesNot \nseriousNot serious SeriousaNot serious Not serious 123 - 1161 58 - 1162• V116 met non -inferiority criteriab for \n9/9 shared and superiority criteriac \nfor 12/12 unique serotypes vs. \nPPSV23\n• V116 met non -inferiority criteriad for \n10/10 shared and superiority \ncriteriae 10/11 unique serotypes vs. \nPCV20\n• V116 had higher immune responses \nfor 1 -4/6 shared and all unique \nserotypes vs. PCV15Moderate CriticalGRADE Summary of Findings Table\nPICO 1: Adults currently recommended to receive PCV\na. These are all immunogenicity studies and there are no correlates of protection for some critical outcomes considered.\nb. Noninferiority for GMT ratio was defined as the lower bound of the 95% CI of the estimated OPA GMT ratio ({V116:PPSV23} to be > 0.33.\nc. Superiority for GMT ratio was defined as the lower bound of the 95% CI of the estimated OPA GMT ratio [V116:PPSV23] to be > 1.0.\nd. Noninferiority for GMT ratio was defined as the lower bound of the 2 sided 95% CI of the OPA GMT ratio [V116 / PCV20] to be > 0.5.\ne. Superiority for GMT ratio was defined as the lower bound of the 2 sided 95% CI of the OPA GMT ratio [V116 / PCV20] to be >2.0.\nReferences\n1. Platt H, Omole T, Cardona J, Fraser NJ, Mularski  RA, Andrews C, Daboul  N, Gallagher N, Sapre A, Li J, Polis A, Fernsler  D, Tamms G, Xu W, Murphy R, Skinner J, Joyce J, Musey L. Safety, tolerability, and immunogenicity of a 21- valent pneumococcal c onjugate vaccine, \nV116, in healthy adults: phase 1/2, randomised, double- blind, active comparator -controlled, multicentre, U.S.- based trial. Lancet Infect Dis. 2023 Feb;23(2):233- 246. doi: 10.1016/S1473- 3099(22)00526 -6. Epub 2022 Sep 15. PMID: 36116461.\n2. V116- 003. A clinical study to evaluate the safety, tolerability, and immunogenicity of V116 compared to PCV20 in pneumococcal vaccine -naïve adults\n3. V116- 006. A Phase 3 Clinical Study to Evaluate the Safety, Tolerability, and Immunogenicity of V116 in Pneumococcal Vaccine- Experienced Adults 50 Years of Age or Older \n4. V116- 007. A Phase 3, Multicenter, Randomized, Double- blind, Active Comparator - Controlled Study to Evaluate the Safety, Tolerabi lity, and Immunogenicity of V116 in Adults Living With HIV\n5. V166- 005. A clinical study comparing the immunogenicity and safety of V116 when administered concomitantly with inactivated infl uenza vaccine \nCertainty assessment № of patients Effect\nCertainty Importance№ of \nstudiesStudy designRisk of \nbiasInconsistency Indirectness ImprecisionOther \nconsiderationsPCV21 comparisonRelative\n(95% CI)Absolute\n(95% CI)\nSerious adverse events following immunization\n61-6Randomized \nstudiesNot \nseriousNot serious Not serious SeriousfNot serious 57/4445\n(1.3%)63/2962\n(2.1%)Absolute % difference for SAEs across \nstudies is -0.8%; two SAEs deemed \nvaccine -relatedg in the V116 group \nreportedModerate CriticalGRADE Summary of Findings Table\nPICO 1: Adults currently recommended to receive PCV\nf. few vaccine- related serious adverse events reported. \ng. Bronchospasm (V116- 005): 50- year-old female in the sequential group with bronchospasm within 30 minutes after the 2ndvaccination (V116); duration 23 hours; resolved; Injection site cellulitis (V116- 006): 67- year-old female in Cohort 1 (prior PPSV23) with i njection site cellulitis \non Day 6; duration 1.57 weeks; resolved (Merck, unpublished).\nReferences\n1. Platt H, Omole T, Cardona J, Fraser NJ, Mularski  RA, Andrews C, Daboul  N, Gallagher N, Sapre A, Li J, Polis A, Fernsler  D, Tamms G, Xu W, Murphy R, Skinner J, Joyce J, Musey L. Safety, tolerability, and immunogenicity of a 21- valent pneumococcal c onjugate vaccine, \nV116, in healthy adults: phase 1/2, randomised, double- blind, active comparator -controlled, multicentre, U.S.- based trial. Lancet Infect Dis. 2023 Feb;23(2):233- 246. doi: 10.1016/S1473- 3099(22)00526 -6. Epub 2022 Sep 15. PMID: 36116461.\n2. V116- 003. A clinical study to evaluate the safety, tolerability, and immunogenicity of V116 compared to PCV20 in pneumococcal vaccine -naïve adults\n3. V116- 006. A Phase 3 Clinical Study to Evaluate the Safety, Tolerability, and Immunogenicity of V116 in Pneumococcal Vaccine- Experienced Adults 50 Years of Age or Older \n4. V116- 007. A Phase 3, Multicenter, Randomized, Double- blind, Active Comparator - Controlled Study to Evaluate the Safety, Tolerabi lity, and Immunogenicity of V116 in Adults Living With HIV \n5. V166- 005. A clinical study comparing the immunogenicity and safety of V116 when administered concomitantly with inactivated infl uenza vaccine\n6. V116- 004. A Phase 3 Randomized, Double- blind, Active Comparator -controlled, Lot to- Lot Consistency Study to Evaluate the Safety,  Tolerability, and Immunogenicity of V116 in Adults 18 to 49 Years of Age. \nCertainty assessment № of patients Effect\nCertainty Importance № of \nstudiesStudy designRisk \nof \nbiasInconsistency Indirectness ImprecisionOther \nconsiderationsPCV21 comparisonRelative\n(95% CI)Absolute\n(95% CI)\nVT-IPD, VT -nonbacteremic pneumococcal pneumonia, VT -pneumococcal mortality outcome (Assessed with: Immunogenicity)\n21-2Randomized \nstudiesNot \nseriousNot serious SeriousaNot serious Not serious 252 - 1161 254 - 1162 • V116 met non -inferiority \ncriteriab for 9/9 shared and \nsuperiority criteriac for 12/12 \nunique serotypes vs. PPSV23\n• V116 met non -inferiority \ncriteriad for 10/10 shared and \nsuperiority criteriae 10/11 \nunique serotypes vs. PCV20Moderate CriticalGRADE Summary of Findings Table\nPICO2: Adults aged 50–64 years, no risk- based indications\na. These are all immunogenicity studies and there are no correlates of protection for some critical outcomes considered.\nb. Noninferiority for GMT ratio was defined as the lower bound of the 95% CI of the estimated OPA GMT ratio ({V116:PPSV23} to be > 0.33.\nc. Superiority for GMT ratio was defined as the lower bound of the 95% CI of the estimated OPA GMT ratio [V116:PPSV23] to be > 1.0.\nd. Noninferiority for GMT ratio was defined as the lower bound of the 2 sided 95% CI of the OPA GMT ratio [V116 / PCV20] to be > 0.5.\ne. Superiority for GMT ratio was defined as the lower bound of the 2 sided 95% CI of the OPA GMT ratio [V116 / PCV20] to be >2.0.\nReferences\n1. Platt H, Omole T, Cardona J, Fraser NJ, Mularski  RA, Andrews C, Daboul  N, Gallagher N, Sapre A, Li J, Polis A, Fernsler  D, Tamms G, Xu W, Murphy R, Skinner J, Joyce J, Musey L. Safety, tolerability, and immunogenicity of a 21-\nvalent pneumococcal conjugate vaccine, V116, in healthy adults: phase 1/2, randomised, double- blind, active comparator -controlled, multicentre, U.S.- based trial. Lancet Infect Dis. 2023 Feb;23(2):233 -246. doi: 10.1016/S1473-\n3099(22)00526 -6. Epub 2022 Sep 15. PMID: 36116461.\n2. V116- 003. A clinical study to evaluate the safety, tolerability, and immunogenicity of V116 compared to PCV20 in pneumococcal vaccine- naïve adults\nCertainty assessment № of patients Effect\nCertainty Importance № of \nstudiesStudy designRisk \nof \nbiasInconsistency Indirectness ImprecisionOther \nconsiderationsPCV21 comparisonRelative\n(95% CI)Absolute\n(95% CI)\nSerious adverse events following immunization\n21-2Randomized \nstudiesNot \nseriousNot serious Not serious SeriousfNot serious 23/1431\n(1.6%)27/1429\n(1.9%)Absolute % difference for SAEs across \nstudies is -0.3%; no vaccine -related \nserious adverse events reportedModerate CriticalGRADE Summary of Findings Table\nPICO2: Adults aged 50–64 years, no risk- based indications\nf. No vaccine -related serious adverse events reported. \nReferences\n1. Platt H, Omole T, Cardona J, Fraser NJ, Mularski  RA, Andrews C, Daboul  N, Gallagher N, Sapre A, Li J, Polis A, Fernsler  D, Tamms G, Xu W, Murphy R, Skinner J, Joyce J, Musey L. Safety, tolerability, and immunogenicity of a 21-\nvalent pneumococcal conjugate vaccine, V116, in healthy adults: phase 1/2, randomised, double- blind, active comparator -controlled, multicentre, U.S.- based trial. Lancet Infect Dis. 2023 Feb;23(2):233 -246. doi: 10.1016/S1473-\n3099(22)00526 -6. Epub 2022 Sep 15. PMID: 36116461.\n2. V116- 003. clinical study to evaluate the safety, tolerability, and immunogenicity of V116 compared to PCV20 in pneumococcal vacc ine-naïve adults\nCertainty assessment № of patients Effect\nCertainty Importance\n№ of \nstudiesStudy designRisk of \nbiasInconsistency Indirectness ImprecisionOther \nconsiderationsPCV21 comparisonRelative\n(95% CI)Absolute\n(95% CI)\nVT-IPD, VT -nonbacteremic pneumococcal pneumonia, VT -pneumococcal mortality outcome (Assessed with: Immunogenicity)\n11Randomized \nstudiesNot \nseriousNot serious SeriousaNot serious Not serious 184 - 198 550 - 575 V116 met criteria for \nimmunobridgingb to 50 -\n64y for all serotypesModerate CriticalGRADE Summary of Findings Table\nPICO3: Adults aged 19–49 years, no risk- based indications\na. These are all immunogenicity studies and there are no correlates of protection for some critical outcomes considered.\nb. Immunobridging for GMT ratio was defined as the lower bound of the 2 sided 95% CI of the OPA GMT ratio [V116 18 to 49 group/V116 50 to 64 gr oup] to be >0.5.\nReferences\n1. V116 -003. A clinical study to evaluate the safety, tolerability, and immunogenicity of V116 compared to PCV20 in pneumococcal vaccine -naïve adults\nCertainty assessment № of patients Effect\nCertainty Importance№ of \nstudiesStudy designRisk \nof \nbiasInconsistency Indirectness ImprecisionOther \nconsiderationsPCV21 comparisonRelative\n(95% CI)Absolute\n(95% CI)\nSerious adverse events following immunization\n11Randomized \nstudiesNot \nseriousNot serious Not serious SeriouscNot serious 1/200\n(0.5%)3/100\n(3.0%)Absolute % difference \nfor SAEs is -2.5%; no \nvaccine -related \nserious adverse events \nreportedModerate CriticalGRADE Summary of Findings Table\nPICO3: Adults aged 19–49 years, no risk- based indications\nc. No vaccine -related serious adverse events reported \nReferences\n1. V116 -003. clinical study to evaluate the safety, tolerability, and immunogenicity of V116 compared to PCV20 in pneumococcal vacc ine-naïve adults\nPICO1: Adults currently recommended to receive PCV\nType Outcome ImportanceIncluded in evidence \nprofile Certainty of evidence\nBenefitsVT- IPD Critical No* Moderate\nVT-pneumonia Critical No* Moderate\nVT- pneumococcal \ndeathsCritical No* Moderate\nHarmsSerious adverse events \nfollowing \nimmunizationCritical Yes Moderate\n*No clinical evidence available; immunogenicity data used as proxy for vaccine effectiveness of outcomes\nPICO2: Adults aged 50 –64 years, no risk -based \nindications\nType Outcome ImportanceIncluded in evidence \nprofile Certainty of evidence\nBenefitsVT- IPD Critical No* Moderate\nVT-pneumonia Critical No* Moderate\nVT- pneumococcal \ndeathsCritical No* Moderate\nHarmsSerious adverse events \nfollowing \nimmunizationCritical Yes Moderate\n*No clinical evidence available; immunogenicity data used as proxy for vaccine effectiveness of outcomes\nPICO3: Adults aged 19– 49 years, no risk -based \nindications\nType Outcome ImportanceIncluded in evidence \nprofile Certainty of evidence\nBenefitsVT- IPD Critical No* Moderate\nVT-pneumonia Critical No* Moderate\nVT- pneumococcal \ndeathsCritical No* Moderate\nHarmsSerious adverse events \nfollowing \nimmunizationCritical Yes Moderate\n*No clinical evidence available; immunogenicity data used as proxy for vaccine effectiveness of outcomes", "summary": "Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. Preliminary Work Group Interpretations of EtR  and  Next Steps February 2024, ACIP Meeting February 29, 2024 Miwako Kobayashi, MD, MPH, FACP , FIDSA 1.Should PCV21 be…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-28-29-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-02-28-29/06-Pneumococcal-Kobayashi-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 57}
{"title": "01 Vaxelis Loehr 508", "content": "Introduction and Terms of Reference:\nCombined Diphtheria and Tetanus Toxoids and Acellular \nPertussis, Inactivated Poliovirus, Haemophilus  influenzae \nType B Conjugate, and Hepatitis B vaccine (Vaxelis) \nJamie Loehr\nInterim Chair, ACIP Meningococcal/Hib Vaccines Work Group\nFebruary 29, 2024National Center for Immunization & Respiratory Diseases\nACIP Meningococcal/Hib Vaccines Work Group\n▪ ACIP Members on the WG\n•Jamie Loehr (Interim Chair)\n•Wilbur Chen\n▪ Ex Officio WG Members\n•Margaret Bash (FDA)\n•Matthew Clark (IHS)\n•Mark Connelly (FDA)\n•Francisco Leyva (NIH)\n▪ WG Liaisons and Consultants\n•Amra Resic  (AAFP)\n•Samir Shah (AAP) \n•Barb Fluty (ACHA)\n•Karyn Lyons (AIM)\n•Paul Cieslak (CSTE)\n•Kathy Hsu (IDSA)\n•Joseline Zafack (NACI)\n•Jeff Goad (NFID)\n•Jessica Cataldi (PIDS)\n•Amy Middleman (SAHM)\n•Kathy Poehling (Wake Forest)\n•Lynn Bahta (Minnesota Department of Health)\n•David Stephens (Emory)▪ CDC Contributors\n•Jennifer Collins (DBD/NCIRD)\n•Sarah Schillie (DBD/NCIRD)\n•Lucy McNamara (DBD/NCIRD)\n•LeAnne Fox (DBD/NCIRD)\n•Susan Hariri (DBD/NCIRD)\n•Amy Rubis (DBD/NCIRD)\n•Noele Nelson (DBD/NCIRD)\n•Alison Albert (DBD/NCIRD)\n•Angela Jiles (DBD/NCIRD)\n•Marc Fischer (DIDRI/NCEZID)\n•Jonathan Duffy (DHQP/NCEZID)\n•Pedro Moro (DHQP/NCEZID)\n•Tanya Myers (DHQP/NCEZID) \n•Liz Velazquez (ISD/NCIRD)\n•Jessica MacNeil (ACIP Secretariat)\n•Hannah Rosenblum (ACIP Secretariat)\n•Melinda Wharton (ACIP Secretariat)\n▪ GRADE/ EtR Support\n•Doug Campos -Outcalt (Arizona)\n•Rebecca Morgan (Case Western Reserve)\n2\nBackground\n▪PRP-OMP ( PedvaxHIB ) is preferentially recommended for American \nIndian and Alaska Native (AI/AN) infants\n•It provides a protective antibody response after the first dose\n•Historically, Hib meningitis peaked at an earlier age among AI/AN \ninfants\n▪Vaxelis (DTaP -IPV-Hib-HepB ) does not currently have a preferential \nrecommendation for AI/AN infants because\n•It contains PRP -OMP in a lower amount than PedvaxHIB\n•Post -dose 1 immunogenicity data were not previously available\n3\nThe use of trade names is for identification purposes only and does not imply endorsement by CDC.\nPolicy question\nShould Vaxelis (DTaP -IPV-Hib-HepB ) be included with \nPedvaxHIB  in the preferential recommendation for \nAmerican Indian and Alaska Native (AI/AN) infants?\n4\nThe use of trade names is for identification purposes only and does not imply endorsement by CDC.\nWork Group activities\n▪Review the epidemiology of invasive Hib disease in AI/AN \npopulations and evidence supporting the existing preferential \nrecommendation for PedvaxHIB\n▪Review clinical trial data on post -dose 1 immunogenicity of Vaxelis \nvs. PedvaxHIB\n▪Develop draft policy recommendation based on grading of \nrecommendations, assessment, development, and evaluation \n(GRADE) and the evidence to recommendations ( EtR) framework\n5The use of trade names is for identification purposes only and does not imply endorsement by CDC.\n6Today’s agenda\nAll topics  will be presented for information and discussionTopic Presenter\nBackground on Hib disease and \nvaccination among American Indian \nand Alaska Native populationsDr. Jennifer Collins (CDC/NCIRD)\nImmunogenicity of H. influenzae type b \nPRP-OMP vaccines in American Indian \nand Alaska Native infantsDr. Laura Hammitt (Johns Hopkins \nBloomberg School of Public Health \n– Center for Indigenous Health)\nWork Group Considerations Dr. Jennifer Collins (CDC/NCIRD) \nNext steps\n24▪Present evidence to recommendations ( EtR) framework and draft \npolicy recommendations for a vote in June\n7", "summary": "Introduction and Terms of Reference: Combined Diphtheria and Tetanus Toxoids and Acellular  Pertussis, Inactivated Poliovirus, Haemophilus  influenzae  Type B Conjugate, and Hepatitis B vaccine (Vaxelis)  Jamie Loehr Interim Chair, ACIP Meningococcal/Hib Vaccines Work Group February 29, 2024National Center for Immunization & Respiratory Diseases ACIP Meningococcal/Hib Vaccines Work Group ▪ ACIP Members on the WG •Jamie Loehr (Interim Chair) •Wilbur Chen ▪ Ex Officio WG Members •Margaret Bash…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-28-29-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-02-28-29/01-Vaxelis-Loehr-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 7}
{"title": "02 Vaxelis Collins 508", "content": "Background on invasive Hib disease and \nvaccination among American Indian and \nAlaska Native populations\nJennifer Collins MD, MSc\nCo-Lead, ACIP Hib/Meningococcal Vaccines Work Group\nFebruary 29, 2024National Center for Immunization & Respiratory Diseases\nBackground\n3▪Gram -negative bacilli \n▪Originally thought to be the cause of influenza\n▪Abbreviated “ H. flu ” or Hi\n▪Infections range from mild to severe invasive disease\nHaemophilus  influenzae \nNTUnencapsulated \n(Non -typeable)\nb a c d e fEncapsulated \n(6 serotypes based on polysaccharide antigens)Classification of H. influenzae\n4\nH. influenzae serotype b (Hib) is most virulent and \nis the only type preventable through vaccination \nNTUnencapsulated \n(Non -typeable)\nb a c d e fEncapsulated \n(6 serotypes based on polysaccharide antigens)\n•Before the introduction of effective vaccines, Hib was the leading cause of \nbacterial meningitis and other invasive bacterial disease in the United \nStates, primarily among children aged <5 years\n5\n6Risk factors for invasive Hib disease in the pre -\nvaccine era\nImmunocompromising conditions\n•HIV infection\n•Asplenia / Sickle cell disease\n•IgG deficiency\n•Early component complement \ndeficiency\n•Hematopoietic  stem cell \ntransplantation\n•ChemotherapyDemographic factors\n•Male sex\n•Race/Ethnicity\n•American Indian\n•Alaska Native\n•Black\n•Social factors\n•Household c rowding\n•Large household size\n•Low SES\n•School -aged siblings\n•Daycare attendance\n6\nBacteremic  \npneumoniaMost common clinical syndromes of invasive Hib \ndisease in the post -vaccine era\nMeningitis Bacteremia \nwithout a focus\n7\nEstimated incidence of invasive Hib disease in children \naged <5 years decreased dramatically  after \nintroduction of Hib vaccines\n051015202530\n1980 1985 1990 1995 2000 2005 2010Estimated \nincidence per \n100,000 \npopulationConjugate vaccine licensed for use \nin children aged ≥18 months\nConjugate vaccine licensed for use \nin infants aged ≥2 monthsPolysaccharide vaccine licensed for \nuse in children aged ≥18 months\n8\n9▪Capsular polysaccharide (PRP) conjugated to carrier proteins\n–Tetanus toxoid (PRP -T)\n–Outer membrane protein of meningococcal serogroup B (PRP -OMP)\n▪Highly immunogenic via activation of T -cell dependent immunity\n–95% of infants develop protective antibody levels after a primary series\n–No cross protection against non -b serotypes/ NTHi\n▪Estimated clinical efficacy 95% ─100% \n▪Invasive Hib disease is uncommon in children who are fully vaccinated Hib polysaccharide conjugate vaccines \nremain the primary prevention strategy for Hib\n9\n10Current Hib vaccines in the United States\nVaccine Product Trade Name Primary series Booster dose\nMonovalent vaccines\nPRP-OMP PedvaxHIB * 2, 4 months 12–15 months\nPRP-T ActHIB 2, 4, 6 months 12–15 months\nPRP-T Hiberix 2, 4, 6 months 12–15 months\nCombination vaccines**\nDTaP -IPV/Hib Pentacel 2, 4, 6 months 12–15 months\nDTaP -IPV-Hib-HepB Vaxelis 2, 4, 6 months ***\n*Recommended vaccine for American Indian/Alaska Native children\n**Hib component of Pentacel  is PRP -T. Hib component of Vaxelis is PRP -OMP .\n***Vaxelis is not recommended for the booster dose. A different Hib -containing vaccine should be administered as a booster at 12 –15 months.\n10\nInvasive Hib disease disproportionately \naffects American Indian and Alaska \nNative populations\n12051015202530\n1980 1985 1990 1995 2000 2005 2010Incidence declined >99%Incidence of invasive Hib disease among children aged \n<5 years declined >99% with introduction of Hib vaccines\n12Estimated \nincidence  per \n100,000 of \ninvasive Hib \ndisease among \nchildren aged \n<5 years\n13050100150200250300\n1980 1985 1990 1995 2000 2005 2010U.S. childrenExpanding the y -axis…\n13Estimated \nincidence  per \n100,000 of \ninvasive Hib \ndisease among \nchildren aged \n<5 years\n14050100150200250300\n1980 1985 1990 1995 2000 2005 2010280\nAmerican Indian and \nAlaska Native \nchildren\nU.S. childrenIncidence among AI/AN children aged <5 years was >10x \nthe incidence among U.S. children aged <5 years overall\n14Estimated \nincidence  per \n100,000 of \ninvasive Hib \ndisease among \nchildren aged \n<5 years\n15Incidence of Hib disease among AI/AN children \naged <5 years declined >98% with Hib vaccination\n050100150200250300\nPre-vaccine era Post-vaccine era\n15Estimated i ncidence  \nper 100,000 of \ninvasive Hib disease \namong AI/AN \nchildren aged \n<5 years\nIncidence per \n100,000 of invasive \nH. influenzae \ndisease by type \namong children \naged <5 years, \n2011 –2020 \n012345\nHia Hib Hif NTHiAI/AN Non-AI/ANIncidence of invasive H. influenzae disease remains \nsubstantially higher among American Indian and \nAlaska Native children  compared with non-Native \nchildren\n5.1\n2.5\n0.92.1\n0.6 0.080.31.3\n16\nIncidence per \n100,000 of invasive \nH. influenzae \ndisease by type \namong children \naged <5 years, \n2011 –2020 \n012345\nHia Hib Hif NTHiAI/AN Non-AI/AN\n17AI/AN children have 31 -fold higher incidence of \ninvasive Hib disease than non -Native children\n31x\nIn the pre -vaccine era, the incidence of Hib meningitis \npeaked at a younger age among AI/AN populations \nthan the general U.S. population \n18 Data from Ward JI, et al.  Lancet . 1981. 1(8233); 1281 –5. Graph credit: Laura Hammitt’s  February 2019 ACIP Meeting presentation \nCases per 100,000\n(1971–1977) \n19Invasive Hib disease among AI/AN children \naged <5 years―Active Bacterial Core \nsurveillance, 2003 –2023*  \nCharacteristic N=28\nPatient age, months\n     Median\n     IQR\n     Range 12\n5–31\n0–56\nUnvaccinated , n (%) 9 (31)\nSyndrome\n     Meningitis\n     Pneumonia\n     Cellulitis\n     Bacteremia without a focus 13 (45)\n12 (41)\n3 (10)\n1 (3)\n19*2022 and 2023 data are preliminary\nHib vaccination among American Indian \nand Alaska Native infants\nBriere EC, et al. Prevention and Control of Haemophilus  influenzae Type b Disease: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recommendations and Reports . 63(RR01);1 -14PedvaxHIB  (PRP-OMP) is preferentially recommended \nfor AI/AN infants\n•Vaccination with a 2 dose primary series of a Hib vaccine that contains \nPRP-OMP ( PedvaxHIB ) is preferred for AI/AN infants to provide early \nprotection because this vaccine produce a protective antibody response \nafter the first dose\n•A booster dose (dose 3) of Hib vaccine is recommended at age 12 \nthrough 15 months; for the booster dose, there is no preferred vaccine \nformulation\n21\n22\nPRP-OMP provides earlier protection\n*PRP ≥0.15 ug/ml and ≥1.0 ug/ml are correlates of short -term, and long -term protection, respectively.\nWatt JP , et al. Global reduction of Hib disease: what are the next steps? The Journal of Pediatrics 2003. 22PRP-OMP produces a \nprotective antibody \nresponse after the \nfirst dose\nAnti-PRP GMT\nµg/mL*\nAfter dose 1\n(age 2 months)Before After dose 2\n(age 4 months)After dose 3\n(age 6 months)Final titers \nare higher \nwith PRP -T\n23The incidence of invasive Hib disease in Alaska \nNative populations increased in late 1990s amid \nvaccine policy changes \nSingleton R et al. The Alaska Haemophilus  influenzae Type b Experience: Lessons in Controlling a Vaccine -Preventable Disease. Pediatrics. 2006 Aug;118(2):e421 -9Invasive Hib disease \nrates per 100 000 in \nAlaska Native and \nnon-Native children \naged 5 years, 1980 –\n2004\n23\n24\nSingleton R et al. The Alaska Haemophilus  influenzae Type b Experience: Lessons in Controlling a Vaccine -Preventable Disease. Pediatrics. 2006 Aug;118(2):e421 -9\nUniversal Hib \nvaccination:\nHbOC  in January \nPRP-OMP in JulyCombination vaccine \nDTP-HbOC  replaced \nPRP-OMP\nChange to PRP -OMP for \ndose 1 followed by HbOC  \nfor doses 2 –4 \nHbOC  = Hib oligosaccharide CRM 197 vaccine\nDTP =  Diphtheria, tetanus toxoids, pertussis Timeline of Hib vaccine policy changes in Alaska\n.Change to PRP -OMP for \nall Hib doses\n24\n25Vaccine status among children aged <10 years \nwith invasive Hib disease in Alaska, 1991 –2004\nSingleton R et al. The Alaska Haemophilus  influenzae Type b Experience: Lessons in Controlling a Vaccine -Preventable Disease. Pediatrics. 2006 Aug;118(2):e421 -9\n▪During  1996–2000 , a greater \nproportion of cases \n–Occurred among Alaska \nNative children\n–Occurred among partially \nimmunized children\n–Were considered true vaccine \nfailures\n25\n26Vaccine administration errors may have \ncontributed to some cases when  both PRP -OMP \nand HbOC  were used\nSingleton R et al. The Alaska Haemophilus  influenzae Type b Experience: Lessons in Controlling a Vaccine -Preventable Disease. Pediatrics. 2006 Aug;118(2):e421 -9▪October 1997 –December 2000\n–14 cases occurred in Alaska Native children aged <5 \nyears\n–3 children (21%) had inadvertently received HbOC  for \ntheir first and only dose\n26\n27Increases in Hib disease in Alaska during \n1996–2000 were attributed to\n▪Use of HbOC , which  did not achieve short -term \nprotective antibody concentrations (0.15 µg/mL) until the \nthird dose\n▪Low rates of on -time immunization\nSingleton R et al. The Alaska Haemophilus  influenzae Type b Experience: Lessons in Controlling a Vaccine -Preventable Disease. Pediatrics. 2006 Aug;118(2):e421 -9 27\n28National Immunization Survey –Child \nEstimated vaccination coverage with Hib full series* by age 24 \nmonths among American Indian or Alaska Native children by \nbirth year\nBirth yearⴕ% 95% CI\n2016 77.0 64.8 –87.4\n2017 69.6 55.1 –83.0\n2018 76.3 66.0 –85.4\n2019 69.9 59.5 –79.7\n2020 67.5 54.6 –79.7\n* Hib Full Series: primary series and booster dose, which includes receipt of ≥3 or ≥4 doses, depending on product type recei ved.\n† Data for the 2016 birth year are from survey years 2017, 2018, and 2019; data for the 2017 birth year are from survey years  2018, 2019, and 2020; data for the \n2018 birth year are from survey years 2019, 2020, and 2021; data for the 2019 birth year are from survey years 2020, 2021, an d 2022; data for the 2020 birth year \nare considered preliminary and are from survey years 2021 and 2022 (2023 data are not yet available).\nHill HA et al. Vaccination Coverage by Age 24 Months Among Children Born in 2019 and 2020 — National Immunization Survey -Child, United States, 2020 –2022 . MMWR Weekly / November 3, 2023 / 72(44);1190 –1196. 28\n29National Immunization Survey –Child: \nIn 2019–2020, American Indian/Alaska Native children were \nless likely than White children to have received the Hib full \nseries* by age 24 months\nRace, Ethnicity 2019–2020 (prelim)ⴕ\n%, 95% CIDifference (White –AI/AN)\n2019–2020 (prelim)ⴕ\n% 95% CI p-value\nWhite, non -Hispanic 80.8 (79.4 –82.1) REF REF REF\nAmerican Indian or Alaska \nNative, non -Hispanic68.7 (60.3 –76.8) 12.1 (3.6–20.5) 0.01\n*Hib full series: primary series and booster dose, which includes receipt of ≥3 or ≥4 doses, depending on product type receiv ed.\nⴕData for the 2019 birth year are from survey years 2020, 2021, and 2022; data for the 2020 birth year are considered prelimin ary and are \nfrom survey years 2021 and 2022 (2023 data are not yet available).\nHill HA et al. Vaccination Coverage by Age 24 Months Among Children Born in 2019 and 2020 — National Immunization Survey -Child, United States, 2020 –2022. MMWR Weekly / November 3, 2023 / 72(44);1190 –1196. 29\nVaxelis (DTaP -IPV-Hib-HepB )\n31Vaxelis (DTaP -IPV-Hib-HepB ) is newer\n▪Licensed in December 2018\n▪ACIP voted to include in VFC in June 2019\n▪More than 6.2 million doses distributed in the United \nStates as of Q4 2023\n*Data provided by the manufacturer.31 The use of trade names is for identification purposes only and does not imply endorsement by CDC.\n32Vaxelis (DTaP -IPV-Hib-HepB ) does not \ncurrently have a preferential recommendation \nfor AI/AN infants\nVaccine Product Trade Name PRP OMP\nPRP-OMP PedvaxHIB 7.5 mcg 125 mcg\nDTaP -IPV-Hib-HepB Vaxelis 3 mcg 50 mcg\n32▪Post -dose 1 immunogenicity data not previously available\n▪Lower dose of PRP -OMP than PedvaxHIB\nThe use of trade names is for identification purposes only and does not imply endorsement by CDC.\n33In Phase III clinical \ntrials, Hib antibody \nresponses after the \n3-dose primary \nseries were non -\ninferior to licensed \ncomparator \nvaccines\n21\nVaxelis group\nControl group \nMarshall GS, et al. Immunogenicity, safety and tolerability of a hexavalent vaccine in infants. Pediatrics 2015;136:e323 –32.33- Vaxelis group received DTaP5 -IPV-Hib-HepB, PCV13, and RV5 at 2, 4, and 6 months of age followed by DTaP5, Hib -OMP, and PCV13 at 15 months of a ge.\n- Control group  received DTaP5 -IPV/Hib,PCV13, and RV5 at 2, 4, and 6 months of age, with HepB  at 2 and 6 months of age, followed by DTaP5, Hib -TT, and PCV13 at 15 months of age.\n- PRP ≥0.15 ug/ml and ≥1.0 ug/ml are correlates of short -term, and long -term protection, respectively.\n- The use of trade names is for identification purposes only and does not imply endorsement by CDC.\n.\n34Safety of Vaxelis (DTaP -IPV-Hib-HepB ) \n34▪In clinical trials, the safety profile was consistent with that of licensed \ncomparator vaccines except higher rate of fever than with DTaP -IPV/Hib  \n(47.1% –47.4% vs. 33.2% –34.4%)1,2; rates of fever -related medical events \nwere similar between groups\n▪Post -licensure analysis of VAERS data from June 26, 2019 – June 16, 2023  \ndid not identify new or unexpected safety issues\n1Marshall GS, et al. Immunogenicity, safety and tolerability of a hexavalent vaccine in infants. Pediatrics 2015;136:e323 –32.\n2Block SL, et al. Lot -to-lot consistency, safety, tolerability and immunogenicity of an investigational hexavalent vaccine in U.S . infants. Pediatr  Infect Dis J 2017;36:202 –8.\n\n35Vaxelis protects against 6 infections with fewer \ninjections\nPediarix  is a combination vaccine that protects against diphtheria, tetanus, pertussis, polio, and hepatitis B.\nDTaP is a vaccine that protects against diphtheria, tetanus, and pertussis. The 4th dose of DTaP is recommended at age 15 –18 months.\nIPV is inactivated polio vaccine.Vaxelis  Vaxelis   VaxelisOption 2 months 4 months 6 months 12–15 \nmonthsTotal shots\n1 Vaxelis Vaxelis Vaxelis PedvaxHIB\nDTaP5\n2 PedvaxHIB\nPediarixPedvaxHIB\nPediarix PediarixPedvaxHIB\nDTaP7\n3 PedvaxHIB\nDTaP\nIPV\nHepBPedvaxHIB\nDTaP\nIPVDTaP\nIPV\nHepBPedvaxHIB\nDTaP12\nThe use of trade names is for identification purposes only and does not imply endorsement by CDC. 35\nPolicy question\n▪Should Vaxelis (DTaP -IPV-Hib-HepB ) be included with \nPedvaxHIB  in the preferential recommendation for \nAmerican Indian and Alaska Native infants?\nThe use of trade names is for identification purposes only and does not imply endorsement by CDC. 36\nAcknowledgments\n▪ ACIP Members on the WG\n– Jamie Loehr (Interim Chair)\n– Wilbur Chen\n▪ Ex Officio WG Members\n– Margaret Bash (FDA)\n– Matthew Clark (IHS)\n– Mark Connelly (FDA)\n– Francisco Leyva (NIH)\n▪ WG Liaisons and Consultants\n– Amra Resic  (AAFP)\n– Samir Shah (AAP) \n– Barb Fluty (ACHA)\n– Karyn Lyons (AIM)\n– Paul Cieslak (CSTE)\n– Kathy Hsu (IDSA)\n– Joseline Zafack (NACI)\n– Jeff Goad (NFID)\n– Jessica Cataldi (PIDS)\n– Amy Middleman (SAHM)\n– Kathy Poehling (Wake Forest)\n– Lynn Bahta (Minnesota Department of Health)\n– David Stephens (Emory)▪ CDC Contributors\n– Lucy McNamara (DBD/NCIRD)\n– Sarah Schillie (DBD/NCIRD)\n– LeAnne Fox (DBD/NCIRD)\n– Susan Hariri (DBD/NCIRD)\n– Amy Rubis (DBD/NCIRD)\n– Noele Nelson (DBD/NCIRD)\n– Alison Albert (DBD/NCIRD)\n– Angela Jiles (DBD/NCIRD)\n– Marc Fischer (DIDRI/NCEZID)\n– Jonathan Duffy (DHQP/NCEZID)\n– Pedro Moro (DHQP/NCEZID)\n– Tanya Myers (DHQP/NCEZID) \n– Liz Velazquez (ISD/NCIRD)\n– Jessica MacNeil (ACIP Secretariat)\n– Hannah Rosenblum (ACIP Secretariat)\n– Melinda Wharton (ACIP Secretariat)\n▪ GRADE/ EtR Support\n– Doug Campos -Outcalt (Arizona)\n– Rebecca Morgan (Case Western Reserve)\nThank you!\nQuestions?", "summary": "Background on invasive Hib disease and  vaccination among American Indian and  Alaska Native populations Jennifer Collins MD, MSc Co-Lead, ACIP Hib/Meningococcal Vaccines Work Group February 29, 2024National Center for Immunization & Respiratory Diseases Background 3▪Gram -negative bacilli  ▪Originally thought to be the cause of influenza ▪Abbreviated “ H. flu ” or Hi ▪Infections range from mild to severe invasive disease Haemophilus  influenzae  NTUnencapsulated  (Non -typeable) b a c d e…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-28-29-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-02-28-29/02-Vaxelis-Collins-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 38}
{"title": "03 Vaxelis Hammitt 508", "content": "The HibVax Study\nImmunogenicity of H. influenzae type b PRP -OMP \nvaccines in American Indian and Alaska Native infants\nLaura Hammitt, MD\nAssociate Professor, JHSPH\nInfectious Disease Program Lead, Center for Indigenous Health\nJohns Hopkins Bloomberg School of Public Health\nOn behalf of the study team in Navajo Nation and Anchorage, Alaska \nDisclosures/Disclaimers\n▪This study was supported in part by a research grant from the Investigator -\nInitiated Studies Program of Merck Sharp & Dohme LLC, a subsidiary of Merck \n& Co., Inc. Rahway, NJ 07065 USA, acting on behalf of a joint venture with Sanofi \nknown as MSP Vaccine Company.\n▪Research grants to my institution from AstraZeneca, Merck, Pfizer, CDC, NIH.\n▪The findings and conclusions in this report are those of the authors and do not \nnecessarily represent the official position of the Indian Health Service or the \nCenters for Disease Control and Prevention.  \n2\nPreferential recommendation for PRP -OMP Hib \nconjugate vaccines in AI/AN infants\n▪Disease at a young age in the \npre-vaccine era\n▪Robust protection following \nthe first dose\n▪Immunogenicity \n▪Efficacy \n▪Re-emergence of Hib disease \nin AN infants following use of \nnon -PRP -OMP vaccines   050010001500200025003000\n0-1 2-3 4-5 6-7 8-9 10-11 12-23 24-48Cases per 100,000\nAge (months)Alaska Native Navajo Nation General US\nWard JI et al., Lancet , 1981; 1281 -1284.H. influenzae  meningitis in children <5 years, \n1971-1977\n3\nPreferential recommendation for PRP -OMP Hib \nconjugate vaccines in AI/AN infants\nTable 3. Efficacy Analysis of H. influenzae Type b OMPC Vaccine*\nTime of Disease OnsetCases of H. \ninfluenzae Efficacy \nEstimatep-value95% CI\nVaccine Placebo\n(n/total) (%)\nAt least 1 dose\nOnset before 18 mo. 1/2588 22/2602 95 <0.001 72-99\nOnset before 15 mo. 0/2588 21/2602 100 <0.001 81-100\nOnset before 2nd dose 0/2588 8/2602 100 0.005 41-100\nTwo doses\nOnset before 18 mo. 1/2056 14/2105 93 <0.001 53-98\nOnset before 15 mo. 0/2056 13/2105 100 <0.001 67-100\n*Intention -to-treat analysis - included all infants enrolled.\nSantosham  et al., N Engl J Med 1991; 324:1767 -17724▪Disease at a young age in the \npre-vaccine era\n▪Robust protection following \nthe first dose\n▪Immunogenicity \n▪Efficacy \n▪Re-emergence of Hib disease \nin AN infants following use of \nnon -PRP -OMP vaccines   \nPreferential recommendation for PRP -OMP Hib \nconjugate vaccines in AI/AN infants\nInvasive Hib Disease Children Aged <5 Years \nAlaska, 1980 - 2018\nFigure courtesy of Rosalyn Singleton; Singleton, et al. J Pediatr  2000; 137:313 -205▪Disease at a young age in the \npre-vaccine era\n▪Robust protection following \nthe first dose\n▪Immunogenicity \n▪Efficacy \n▪Re-emergence of Hib disease \nin AN infants following use of \nnon -PRP -OMP vaccines   \nInvasive Hib disease in children <5 years\n020406080100Incidence \n(cases/per 100,000)Navajo Nation General US*Hib PRP -OMP \nvaccine introductionAverage number Hib cases in U5 children \nper year in Navajo Nation:\n1988 - 1990: 19 cases/ yr\n1993 - 2023: <2 cases/yr\n90% \ndecline\nCIH/Navajo Epidemiology Center Active Bacterial Surveillance data; Navajo Research Conference 20216\nInvasive Hib disease in AI/AN children <5 years\nNavajo Nation and White Mountain Apache Tribal Lands \n2004 -2023 (N=25)\n0102030405060Age (months)Vaccination history in Hib cases \n<5 years\nUn-\nvaccinated \n(n=4)Up to date \nfor age \n(n=7)Fully \nvaccinated \n(n=14)Average age 21 months\nMedian age \n(IQR)14 months\n(9-37 months)\nAge range 2-52 months\nClinical \nsyndromeMeningitis: 28%\nPneumonia: 40%\n7IQR: interquartile range\nCombination vaccines → fewer shots, fewer missed doses, \nlower administrative burdenPedvaxHIB ®\n(PRP -OMP Hib vaccine)Vaxelis® \n(DTaP -IPV-Hib-HepB )\nContents Single Antigen Hexavalent\nUse in AI/AN \ninfantsCurrently recommended Hib \nvaccine for AI/AN infantsCurrently recommended for \ngeneral U.S. infants; not yet \npreferentially recommended \nfor AI/AN infants\nHib Antigen and \nConjugate7.5 µg PRP \nOMP3.0 µg PRP \nOMP\nPrimary Series 2-dose (2, 4 months) 3-dose (2, 4, 6 months)\nPost -dose 1 \nimmunogenicityHigh ???\n8PRP: Hib polyribosylribitol  phosphate ; OMP: outer membrane protein of Neisseria meningitidis\nHibVax  Study: Primary objective\nDo Hib antibody levels in AI/AN infants m eet \nnon-inferiority  criteria 30 days after dose 1 of \nVaxelis ® compared to PedvaxHIB ®?\n9\nHibVax  Study Overview\nPhase IV, prospective, open label, RCT\n2 months\nVisit 1\nDay 13 months\nVisit 2\nDay 31\n 6 months\nVisit 4\nDay 1217 months\nVisit 5\nDay 151\n4 months\nVisit 3\nDay 61\nPhysical exam\nQuestionnaire\nReceive vaccinesBlood draw\nCollection Window30-48 Days \nPost Dose 156-90 Days \nPost Dose 230-48 Days \nPost Dose 3Prior to \nDose 1Safety monitoring\nNCT04978818;  JHSPH IRB #11170; Navajo Nation Human Research Review Board #20.374; Alaska Area IRB #2020 -20-01110\n\nHibVax  Study Overview\nPhase IV, prospective, open label, RCT\n2 months\nVisit 1\nDay 13 months\nVisit 2\nDay 31\n 6 months\nVisit 4\nDay 1217 months\nVisit 5\nDay 151\n4 months\nVisit 3\nDay 61\nPhysical exam\nQuestionnaire\nReceive vaccinesBlood draw\nCollection Window30-48 Days \nPost Dose 156-90 Days \nPost Dose 230-48 Days \nPost Dose 3Prior to \nDose 1Safety monitoring\nNCT04978818;  JHSPH IRB #11170; Navajo Nation Human Research Review Board #20.374; Alaska Area IRB #2020 -20-01111\n\nHibVax  Study Overview\nPhase IV, prospective, open label, RCT\n2 months\nVisit 1\nDay 13 months\nVisit 2\nDay 31\n 6 months\nVisit 4\nDay 1217 months\nVisit 5\nDay 151\n4 months\nVisit 3\nDay 61\nPhysical exam\nQuestionnaire\nReceive vaccinesBlood draw\nCollection Window30-48 Days \nPost Dose 156-90 Days \nPost Dose 230-48 Days \nPost Dose 3Prior to \nDose 1Safety monitoring\nNCT04978818;  JHSPH IRB #11170; Navajo Nation Human Research Review Board #20.374; Alaska Area IRB #2020 -20-01112\n\nInclusion Criteria\n•Healthy AI/AN infant born at gestational age of ≥35 weeks\n•Between 6 to 12 weeks of age \n•Written informed consent provided by parent(s)/Legally \nAuthorized Representative(s) \nExclusion Criteria (selected)\n•Prior receipt of infant vaccines other than birth dose hepatitis B \nvaccine\n•History of receipt of blood, blood products, or antibody products\n•Immunocompromised\n•Allergy to any vaccine component, or to latex\n•Acute illness and/or fever ≥38.0ºC (time -limited exclusion)\n13\nMethods\n▪Anti -Hib IgG antibody levels measured by commercially available \nELISA assay at CDC/Arctic Investigations Program, Anchorage, AK\n▪Geometric mean concentrations (GMCs) assessed using \nconstrained longitudinal analysis (cLDA)\n▪Assumes groups have equal anti -Hib GMC at baseline based on the \nrandomized study design\n▪Results are presented for all evaluable participants complying \nwith the procedures and intervals between primary doses, as \ndefined in the protocol\n14\nStudy Enrollment\n▪Enrollment began in Jan 2022 in \nAnchorage, AK and four sites in the \nNavajo Nation (Southwest US)\n▪All s tudy visits competed by Oct 2023 \nTotal enrollment 333\nAnchorage, AK 26\nChinle , AZ 61\nFort Defiance, AZ 115\nGallup, NM 81\nShiprock, NM 50\n15\nStudy Visit Completion\n2 months \nDay 1 \nN3 months\nDay 31\nN4 months\nDay 61\nN6 months\nDay 121\nN7 months\nDay 151\nN\nCompleted Visit 333 319 314 300 296\nEvaluable Sample 321 307 - 272 270\nEvaluable Sample in ATP Cohort 321 298 - 255 245\nATP: According to protocol\nNo specimens were collected at Day 61, in accordance with the protocol\n16\nParticipant Characteristics\nPedvaxHIB ® (N=166) Vaxelis ® (N=167)\nMedian age in days at Dose 1, \n(interquartile range)56 (45 -63) 60 (46 -63)\nMale, n (%) 74 (44.6) 84 (50.3)\nSite, n (%)\nAnchorage, AK 13 (7.8) 13 (7.8)\nChinle, AZ 30 (18.1) 31 (18.6)\nFort Defiance, AZ 57 (34.3) 58 (34.7)\nGallup, NM 40 (24.1) 41 (24.6)\nShiprock, NM 26 (15.7) 24 (14.4)\n17\nSerious Adverse Events (SAEs)\n▪25 SAEs were detected during study follow up in 21 individuals. \n▪No SAEs were associated with study participation.\n▪The most common SAE was acute respiratory infection (n=21).PedvaxHIB ®\nN=166Vaxelis ®\nN=167Total\nSAEs, n 15 10 25\nParticipants, n (%) 12 (7%) 9 (5%) 21 (6%)\n18\nPrimary Outcome: Anti -Hib IgG Geometric Mean \nConcentration (GMC) 30 Days Post -Dose 1\nPedvaxHIB ® Vaxelis ®\nAnti -Hib Antibody GMC \nµg/mL (95% CI)Observed Data0.39\n(0.31 - 0.50)0.41\n(0.33 - 0.52)\nModeled by \ncLDA0.40 \n(0.31 - 0.50)0.41 \n(0.33 - 0.51)\nRatio of GMCs ( Vaxelis  : PedvaxHib )\n1.03 (0.75 - 1.41)\nThe pre -specified non -inferiority criterion was met based on the lower bound of \nthe 95% confidence interval (CI) around the antibody concentration ratio \n[Vaxelis / PedvaxHIB] being > 0.67CI: confidence interval; cLDA : constrained longitudinal data analysis\n19\nAnti -Hib IgG Geometric Mean Concentration\nDay 1 and Day 31\nOutput from constrained longitudinal data analysis20Putative Correlates of Protection\nLong -term\nShort -term\n\nDose 2Dose 3 (Vaxelis Only)Dose 1Anti -Hib IgG Geometric Mean Concentration\nDays 1, 31, 121, and 151\nPutative Correlates of Protection\nLong -term\nShort -term\nOutput from constrained longitudinal data analysis21\n020406080100\nDay 1 Day 31 Day 121 Day 151ProportionPedvaxHIB\nVaxelisProportion with Anti -Hib Concentration ≥0.15 µg/mL \n22\n020406080100\nDay 1 Day 31 Day 121 Day 151ProportionPedvaxHIB\nVaxelis\n* χ2 p-value <0.05*Proportion with Anti -Hib Concentration ≥1.0 µg/mL \n23\n020406080100\nDay 31:Day 1 Day 121:Day 1 Day 151:Day 1ProportionPedvaxHIB\nVaxelisProportion with 4-fold rise  in Anti -Hib Concentration \nfrom Day 1\n24\nLimitations\n▪Participant follow -up ended at 7 months\n▪Over 90% of participants had anti -Hib antibody above the \nputative correlate of short -term protection\n▪The proportion of participants with anti -Hib antibody \nconcentrations above the putative correlate of long -term \nprotection and the anti -Hib GMC were greater in the Vaxelis ® \ngroup\n25\nProtection Post -Booster\n▪Median age of Hib disease in AI/AN children in the \nSouthwest US: 14 months\n▪Majority of cases occur in fully vaccinated children\n▪Current booster strategy for AI/AN children: PedvaxHib  at 12 -\n15 months\n▪Robust immunogenicity seen in heterologous schedules of \nPRP -OMP followed by conjugate vaccines with different \ncarrier proteins (e.g. PRP -TT, HbOC )\nReid et al. , 1993; Decker et al.,  1993; Decker and Edwards, 1998; Greenberg et al., 1995; Wilck et al., 202126\nWilck  MB et al. Vaccine. 2021;39(9):1428 -1434. doi:10.1016/j.vaccine.2021.01.046Significantly \nhigher \npost -booster \nanti-Hib GMC \nwith a \nheterologous \nbooster \ndose\nVaxelis + \nPRP -TT4 doses \nPRP -TT\n27\nConclusions\n▪Post -dose 1 anti -Hib GMCs following Vaxelis ® met the \npre-specified criteria for non -inferiority. \n▪Including Vaxelis ® among the vaccines with a \npreferential recommendation would expand the \navailable options for AI/AN children. \n28\nAcknowledgements\n▪Study participants and their families\n▪Institutional Review Boards\n▪Navajo Nation Human Research Review Board (NNR -20.374)\n▪Fort Defiance Indian Hospital IRB\n▪Johns Hopkins Bloomberg School of Public Health IRB (IRB00011170)\n▪Alaska Area IRB (2020 -02-011-4)\n▪Southcentral Foundation Executive Committee\n▪Alaska Native Tribal Health Consortium Human Research Review Committee\n▪Indian Health Service, Tséhootsooí  Medical Center, Alaska Native \nMedical Center, CDC/Arctic Investigations Program\n▪Study Team – Bianca Jackson, Bob Weatherholtz , Scott Zeger , Ros \nSingleton, Karen Miernyk , Jonathan Steinberg, James Keck, Study \nNurses, Study Physicians, Regulatory Coordinators, Research \nAssistants\n29", "summary": "The HibVax Study Immunogenicity of H. influenzae type b PRP -OMP  vaccines in American Indian and Alaska Native infants Laura Hammitt, MD Associate Professor, JHSPH Infectious Disease Program Lead, Center for Indigenous Health Johns Hopkins Bloomberg School of Public Health On behalf of the study team in Navajo Nation and Anchorage, Alaska  Disclosures/Disclaimers ▪This study was supported in part by a research grant from the Investigator - Initiated Studies Program of Merck Sharp & Dohme LLC,…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-28-29-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-02-28-29/03-Vaxelis-Hammitt-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 29}
{"title": "04 Vaxelis Collins 508", "content": "Work Group Considerations\nJennifer Collins MD, MSc\nCo-Lead, ACIP Hib/Meningococcal Vaccines Work Group\nFebruary 29, 2024National Center for Immunization & Respiratory Diseases\nPolicy question\n▪Should Vaxelis (DTaP -IPV-Hib-HepB ) be included with \nPedvaxHIB  in the preferential recommendation for \nAmerican Indian and Alaska Native infants?\n2\n3▪574 federally recognized tribes in the United States\n–Listening to tribal communities is very important\n–CDC’s Office of Tribal Affairs and Strategic Alliances \n(OTASA) is helping facilitate \n▪ACIP preferential recommendations must be evidence -\nbasedWork Group Considerations\n3\n4▪80 attendees, including\n–9 from tribes or tribal serving organizations\n–46 from Indian Health Service (IHS)\n▪Key questions and concerns raised by participants\n–Will Vaxelis offer the same protection as PedvaxHIB ? \n–Need to monitor for possible breakthrough cases\n–Safety and side effectsCDC/NCIRD held a listening session with tribal \ncommunities in January 2024\n4 The use of trade names is for identification purposes only and does not imply endorsement by CDC.\nKey considerations regarding post -dose 1 \nimmunogenicity of Vaxelis among American \nIndian and Alaska Native populations\n6Study enrollment included Navajo Nation and \nAlaska Native infants\n6\n\n7Anti-Hib GMC 30 days post -dose 1 was \nnon-inferior after Vaxelis vs. PedvaxHIB\n7 The use of trade names is for identification purposes only and does not imply endorsement by CDC.\n\n8\nGMC differences on day 151 post -dose 1 likely \nreflect the 3rd primary series dose of Vaxelis\n8 The use of trade names is for identification purposes only and does not imply endorsement by CDC.\n9\nGMC titers not available beyond day 151 to \nassess longer -term protection in this population \n9 The use of trade names is for identification purposes only and does not imply endorsement by CDC.\n10▪Having a second preferred Hib vaccine option that is a combination vaccine \nmay improve equity and reliability of vaccine supply\n▪Immunologic data are reassuring, however\n–Some concern about generalizing to broader AI/AN populations, though \nprecedent for this with preferential recommendation for PedvaxHIB\n–Lack of direct vaccine effectiveness data\n–Study did not collect titers beyond infancy re: whether Vaxelis might \nbetter prevent residual cases occurring pre -booster\n–Some uncertainty as to why AI/AN populations are particularly affected \nby changes in vaccination type; potentially more than just antibody \nresponse?Additional Work Group Considerations\n10 The use of trade names is for identification purposes only and does not imply endorsement by CDC.\n11▪Including Vaxelis as a second preferred option for AI/AN populations may \nimprove equity and reliability of vaccine supply\n▪Post -dose 1 GMCs of Vaxelis appear non -inferior to that of PedvaxHIB  \namong Navajo Nation and Alaska Native populations \n▪Data gaps\n–Studies in broader AI/AN populations \n–Short -term efficacy\n–Longer -term immunogenicity and efficacy\n▪Next steps\n–GRADE/ EtR framework to be presented in June\n–Plan for vote in JuneFinal reflections and next steps\n11 The use of trade names is for identification purposes only and does not imply endorsement by CDC.\nAcknowledgments\n▪ ACIP Members on the WG\n– Jamie Loehr (Interim Chair)\n– Wilbur Chen\n▪ Ex Officio WG Members\n– Margaret Bash (FDA)\n– Matthew Clark (IHS)\n– Mark Connelly (FDA)\n– Francisco Leyva (NIH)\n▪ WG Liaisons and Consultants\n– Amra Resic  (AAFP)\n– Samir Shah (AAP) \n– Barb Fluty (ACHA)\n– Karyn Lyons (AIM)\n– Paul Cieslak (CSTE)\n– Kathy Hsu (IDSA)\n– Joseline Zafack (NACI)\n– Jeff Goad (NFID)\n– Jessica Cataldi (PIDS)\n– Amy Middleman (SAHM)\n– Kathy Poehling (Wake Forest)\n– Lynn Bahta (Minnesota Department of Health)\n– David Stephens (Emory)▪ CDC Contributors\n– Lucy McNamara (DBD/NCIRD)\n– Sarah Schillie (DBD/NCIRD)\n– LeAnne Fox (DBD/NCIRD)\n– Susan Hariri (DBD/NCIRD)\n– Amy Rubis (DBD/NCIRD)\n– Noele Nelson (DBD/NCIRD)\n– Alison Albert (DBD/NCIRD)\n– Angela Jiles (DBD/NCIRD)\n– Marc Fischer (DIDRI/NCEZID)\n– Jonathan Duffy (DHQP/NCEZID)\n– Pedro Moro (DHQP/NCEZID)\n– Tanya Myers (DHQP/NCEZID) \n– Liz Velazquez (ISD/NCIRD)\n– Jessica MacNeil (ACIP Secretariat)\n– Hannah Rosenblum (ACIP Secretariat)\n– Melinda Wharton (ACIP Secretariat)\n▪ GRADE/ EtR Support\n– Doug Campos -Outcalt (Arizona)\n– Rebecca Morgan (Case Western Reserve)\nThank you!\nQuestions?", "summary": "Work Group Considerations Jennifer Collins MD, MSc Co-Lead, ACIP Hib/Meningococcal Vaccines Work Group February 29, 2024National Center for Immunization & Respiratory Diseases Policy question ▪Should Vaxelis (DTaP -IPV-Hib-HepB ) be included with  PedvaxHIB  in the preferential recommendation for  American Indian and Alaska Native infants? 2 3▪574 federally recognized tribes in the United States –Listening to tribal communities is very important –CDC’s Office of Tribal Affairs and Strategic…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-28-29-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-02-28-29/04-Vaxelis-Collins-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 13}
{"title": "01 Meningococcal Poehling 508", "content": "ACIP Meningococcal Vaccines Work Group \nIntroduction\nKatherine Poehling, MD, MPH\nChair, ACIP Meningococcal Vaccines Work Group\nOctober 25, 2023National Center for Immunization & Respiratory Diseases\nMeningococcal Vaccines Work Group\n▪ ACIP Members on the WG\n•Katherine Poehling (Chair)\n•Lynn Bahta\n•Jamie Loehr\n▪ Ex Officio WG Members\n•Margaret Bash (FDA)\n•Mark Connelly (FDA)\n•Francisco Leyva (NIH)\n▪ WG Liaisons and Consultants\n•Amra Resic (AAFP)\n•Samir Shah (AAP) \n•Sharon McMullen (ACHA)\n•Cacky Tate / Karyn Lyons (AIM)\n•Paul Cieslak (CSTE)\n•Kathy Hsu (IDSA)\n•Joseline Zafack (NACI)\n•Jeff Goad (NFID)\n•Jessica Cataldi (PIDS)\n•Amy Middleman (SAHM)\n•David Stephens (Emory)▪ CDC Contributors\n•Jennifer Collins (DBD/NCIRD)\n•Sam Crowe (DBD/NCIRD)\n•Lucy McNamara (DBD/NCIRD)\n•Ismael Ortega -Sanchez (DVD/NCIRD)\n•Andrew Leidner (ISD/NCIRD)\n•LeAnne Fox (DBD/NCIRD)\n•Susan Hariri (DBD/NCIRD)\n•Amy Rubis (DBD/NCIRD)\n•Noele Nelson (DBD/NCIRD)\n•Alison Albert (DBD/NCIRD)\n•Angela Jiles (DBD/NCIRD)\n•Jonathan Duffy (DHQP/NCEZID)\n•Tanya Myers (DHQP/NCEZID) \n•Liz Velazquez (ISD/NCIRD)\n•Jessica MacNeil (ACIP Secretariat)\n•Melinda Wharton (ACIP Secretariat)\n▪ GRADE/EtR Support\n•Doug Campos -Outcalt (Arizona)\n•Rebecca Morgan (Case Western Reserve)\n2\nPolicy topics under consideration by Work \nGroup regarding Pfizer’s pentavalent vaccine\n▪Should pentavalent vaccine be included as an option for \nMenACWY /MenB vaccination in people currently recommended to \nreceive both vaccines ?  \n▪Should pentavalent vaccine be included as an option for people currently \nrecommended to receive MenACWY only ?  \n▪Should pentavalent vaccine be included as an option for people currently \nrecommended to receive MenB only ? \n3\nSummary of ACIP meetings\n▪February 2023\n–Epidemiology of meningococcal disease in the United States\n–Pfizer’s MenABCWY vaccine clinical trials data\n–Work group interpretation of Pfizer’s MenABCWY trials data\n▪June 2023\n–CDC’s cost effectiveness model\n–Summary of GRADE and EtRframework\n4\nMeningococcal Work Group Meeting Review\nJune─October 2023\n▪Feedback from June ACIP meeting\n–Review of meningococcal schedule postponed to allow for consideration \nof GSK’s forthcoming pentavalent vaccine and availability of data about \npost -COVID meningococcal epidemiology\n▪Comparisons of cost -effectiveness models\n▪Updates on CDC cost -effectiveness model with new price estimate \n–Price for pentavalent was ~$40 –90  more than MenB and now is similar\n▪Discussed 3 potential recommendation options based on concerns raised by \nACIP members in June and new cost -effectiveness estimates\n5\nWork Group determinations for policy questions\n▪Should the pentavalent vaccine be included as an option for MenACWY /MenB\nvaccination in people currently recommended to receive both vaccines ?  \n•YES (strong consensus)\n▪Should the pentavalent vaccine be included as an option for people currently \nrecommended to receive MenACWY only ?  \n•NO (strong consensus)\n▪Should the pentavalent vaccine be included as an option for people currently \nrecommended to receive MenB only ? \n•Perhaps (limited consensus)\n6\nToday’s agenda\n▪Meningococcal Vaccines Session\n▪Later today\n–Meningococcal vote regarding Pfizer’s MenABCWY vaccine\n–Meningococcal VFC vote regarding Pfizer’s MenABCWY vaccine\n7Topic Presenter\nPlan for revisiting the adolescent schedule for \nmeningococcal vaccines Dr. Lucy McNamara (CDC/NCIRD)\nComparison of Pfizer and CDC cost effectiveness \nanalyses for Pfizer’s MenABCWY vaccineDr. Ismael Ortega -Sanchez (CDC/NCIRD)\nSummary of EtRand proposed recommendations for \nPfizer’s MenABCWY vaccineDr. Jennifer Collins (CDC/NCIRD) \nVaccines for Children Resolution Dr. Jeanne Santoli (CDC/NCIRD)", "summary": "ACIP Meningococcal Vaccines Work Group  Introduction Katherine Poehling, MD, MPH Chair, ACIP Meningococcal Vaccines Work Group October 25, 2023National Center for Immunization & Respiratory Diseases Meningococcal Vaccines Work Group ▪ ACIP Members on the WG •Katherine Poehling (Chair) •Lynn Bahta •Jamie Loehr ▪ Ex Officio WG Members •Margaret Bash (FDA) •Mark Connelly (FDA) •Francisco Leyva (NIH) ▪ WG Liaisons and Consultants •Amra Resic (AAFP) •Samir Shah (AAP)  •Sharon McMullen (ACHA) •Cacky…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-25-26-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-10-25-26/01-Meningococcal-Poehling-508.pdf", "doc_date": "2023-10-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 7}
{"title": "02 Meningococcal McNamara 508", "content": "Plan for revisiting the adolescent schedule \nfor meningococcal vaccines\nLucy McNamara, PhD, MS\nInterim Co -Lead, ACIP Meningococcal Vaccines Work Group\nOctober 25, 2023National Center for Immunization & Respiratory Diseases\nConsiderations for routine schedule discussed \nduring June 2023 ACIP meeting\n▪Strong interest in revisiting the meningococcal vaccine schedule, including\n–Whether 11 –12-year old dose is still needed given recent epidemiology \n–Revisiting SCDM for B vaccines\n•Pentavalent vaccines may complicate the SCDM discussion for providers\n•Nuances such as short duration of B protection may be lost in favor of \ngiving a single injection\n▪Opportunity to reduce number of vaccines (i.e., with pentavalent vaccines) is \nappealing if maintaining a high level of protection \n2\nThe Meningococcal Vaccines WG plans to \nrevisit the schedule over the next year to \nensure\n▪Adequate time to perform GRADE and EtRassessments\n▪Assessment of extended interval data for pentavalent vaccines\n▪Integration of any changes into the overall child and adolescent \nimmunization schedule \n▪Assessment of post -COVID epidemiology\n3\nProposed key questions\n▪Should the MenACWY series recommendations be changed to \n–Begin at an older age than currently recommended (11 –12 years)\n–Eliminate the 11 –12 year -old dose or change this recommendation to \nSCDM?\n▪Should the MenB series recommendations be changed to\n–Alter the recommended ages or dosing interval to provide better \nprotection for individuals aged 18 –19  years?\n–Revisit the SCDM recommendation for some or all adolescents (e.g., \nthose planning to attend college)?\n▪Are there ways we can better integrate MenACWY and MenB vaccine \nschedules to streamline administration/increase feasibility?\n4\nDate Topics\nFeb 2024 -Terms of reference for schedule change\nJune 2024-Epidemiology pertinent to possible schedule changes \n•Cases/deaths averted by MenACWY dose at 11 –12y \n•Meningococcal disease burden stratified by race/ethnicity in adolescents\n•Risk factors for serogroup B meningococcal disease among college vs. non -\ncollege students\n•Breakthrough meningococcal disease cases in vaccinated individuals\n•Extended interval data for pentavalent vaccines\nOct 2024 -GRADE/ EtRfor changes to MenACWY and MenB adolescent schedules\n-CE analysis for changes to MenACWY and MenB adolescent schedules\nFeb 2025 -VotesTentative timeline for ACIP meetings, 2024 –2025\n5\nAcknowledgments\n▪ ACIP Members on the WG\n– Kathy Poehling (Chair)\n– Lynn Bahta\n– Jamie Loehr\n▪ Ex Officio WG Members\n– Margaret Bash (FDA)\n– Mark Connelly (FDA)\n– Francisco Leyva (NIH)\n▪ WG Liaisons and Consultants\n– Amra Resic (AAFP)\n– Samir Shah (AAP) \n– Sharon McMullen (ACHA)\n– Cacky Tate / Karyn Lyons (AIM)\n– Paul Cieslak (CSTE)\n– Kathy Hsu (IDSA)\n– Joseline Zafack (NACI)\n– Jeff Goad (NFID)\n– Jessica Cataldi (PIDS)\n– Amy Middleman (SAHM)\n– David Stephens (Emory)▪ CDC Contributors\n– Jennifer Collins (DBD/NCIRD)\n– Sam Crowe (DBD/NCIRD)\n– Ismael Ortega -Sanchez (DVD/NCIRD)\n– Andrew Leidner (ISD/NCIRD)\n– LeAnne Fox (DBD/NCIRD)\n– Susan Hariri (DBD/NCIRD)\n– Amy Rubis (DBD/NCIRD)\n– Noele Nelson (DBD/NCIRD)\n– Alison Albert (DBD/NCIRD)\n– Angela Jiles (DBD/NCIRD)\n– Jonathan Duffy (DHQP/NCEZID)\n– Tanya Myers (DHQP/NCEZID) \n– Liz Velazquez (ISD/NCIRD)\n– Jessica MacNeil (ACIP Secretariat)\n– Melinda Wharton (ACIP Secretariat)\n▪ GRADE/EtR Support\n– Doug Campos -Outcalt (Arizona)\n– Rebecca Morgan (Case Western Reserve)\n6\nThank you! \nQuestions?", "summary": "Plan for revisiting the adolescent schedule  for meningococcal vaccines Lucy McNamara, PhD, MS Interim Co -Lead, ACIP Meningococcal Vaccines Work Group October 25, 2023National Center for Immunization & Respiratory Diseases Considerations for routine schedule discussed  during June 2023 ACIP meeting ▪Strong interest in revisiting the meningococcal vaccine schedule, including –Whether 11 –12-year old dose is still needed given recent epidemiology  –Revisiting SCDM for B vaccines •Pentavalent…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-25-26-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-10-25-26/02-Meningococcal-McNamara-508.pdf", "doc_date": "2023-10-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 7}
{"title": "final posted 2025 12 04 7pm 508", "content": "MEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)    \nAGENDA  \n   \n \nThursday, December 4, 2025   \n   \n8:00 AM    Welcome , Roll Call , and Opening Statement  Dr. Robert Malone  \n(ACIP Vice Chair)      \nDr. Mina Zadeh  \n(ACIP Executive Secretary, CDC)     \n         \n8:30 AM     Hepatitis B  – Recap  Dr. Robert Malone  \n(ACIP Vice Chair)      \n  \n Policy Context and Schedule Comparison   Dr. Vicky Pebsworth   \n(ACIP Childhood and Adolescent \nImmunization Schedule Workgroup \nChair)    \n  \n Burd en of Disease  Dr. Cynthia Nevison  (Presenter )   \n   \n  \n HBV Vaccine Safety  Mr. Mark Blaxill  (CDC )  \n \n   \n Discussion (ACIP members and ex officios)     \n \n Discussion ( Liaisons)   \n \n          \n10:40 AM   Hepatitis B Vaccine  Manufacturers     Dr. Candice Robinson (GSK)  \nDr. Michelle Goveia (Merck)  \nDr. Ayman Chit (Sanofi)   \n   \nQ&A (ACIP members, ex -officios, liaisons)     \n  \n   \n11:05 AM   Lunch   \n \n         \n  \n11:35 AM    Hepatitis B Vaccines  (continued)    \n \n Summary of the Information and Presentation  \nof the Vo t e Language  Dr. Vicky Pebsworth  \n(ACIP  Childhood and Adolescent \nImmunization  Schedule  Workgroup \nChair)  \n \n VFC Presentation    Dr. Jeanne Santoli  (CDC )  \n \n CMS Comments     Mr. Andrew Johnson   \n(CMS , ACIP ex officio )  \n \n Discussion (ACIP members and ex officios)     \n \n Discussion (Liaisons)   \n \n   \n1:50 PM \n Perspectives from People with Lived Experience   \n \n \n   \n2:00 PM \n Public Comments     \n   \n2:30 PM   \n  Votes    Dr. Robert Malone (ACIP Vice Chair)  \n Hepatitis B Vaccine  \n   \n Hepatitis B Vaccine - VFC    \n      \n   \n3:15 PM Coverage Implications  \n  \n VFC Comments  \n Dr. Georgina Peacock (CDC/NCIRD)  \n CMS Comments  \n Mr. Andrew Johnson  \n(CMS , ACIP ex officio ) \n   \n3:25 PM  \n Break   \n   \n3:30 PM   \n Update on Work Groups   \n Dr. Robert Malone (ACIP Vice Chair)   \n   \n3:35 PM Agency Updates  CDC, CMS, FDA, HRSA, IHS, NIH    \n \n   \n3:45 PM   Adjourn        \n  \n \nFriday December 5, 2025   \n         \n8:00 AM  Welcome  and Roll Call     Dr. Robert Malone  \n(ACIP Vice Chair )    \nDr. Mina Zadeh  \n(ACIP Executive Secretary, CDC)    \n  \n   \n8:20 AM  \n Hepatitis B Vaccine Discussion and Votes    Dr. Vicky Pebsworth  \n(ACIP Childhood and Adolescent \nImmunization Schedule \nWorkgroup Chair)  \n Discussion (ACIP members and ex officios)   \n Discussion (Liaisons)   \n VFC presentation  Dr. Jeanne Santoli (CDC)  \n V ote: Hepatitis B Vaccine  Dr. Robert Malone  \n(ACIP Vice Chair)  \n V ote: Hepatitis B Vaccine - VFC        \n   \n10:20 AM  Break   \n   \n10:30 AM    Childhood/Adolescent Immunization Schedule    \nEvolution of the Childhood/Adolescent Vaccination \nSchedule in the U.S. and Vaccine Schedule Comparison: \nU.S. and other Developed Countries   Mr. Aaron Siri (Presenter)     \n Discussion (ACIP members and ex officios)        \n Discussion (Liaisons)   \n   \n12:40 PM  Lunch   \n   \n1:10 PM \n U.S. vs. Danish Vaccine Schedule    Dr. Tracy Beth Hoeg  \n(FDA, ACIP ex officio)  \n \n Discussion (ACIP members and ex officios)   \n Discussion (Liaisons)   \n      \n2:30 PM Adjourn", "summary": "MEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)     AGENDA         Thursday, December 4, 2025        8:00 AM    Welcome , Roll Call , and Opening Statement  Dr. Robert Malone   (ACIP Vice Chair)       Dr. Mina Zadeh   (ACIP Executive Secretary, CDC)                8:30 AM     Hepatitis B  – Recap  Dr. Robert Malone   (ACIP Vice Chair)           Policy Context and Schedule Comparison   Dr. Vicky Pebsworth    (ACIP Childhood and Adolescent  Immunization Schedule Workgroup …", "source_url": "https://www.cdc.gov/acip/meetings/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/agendas/final-posted-2025-12-04-7pm-508.pdf", "doc_date": "2025-12-04", "case": "acip", "sub_case": "agendas", "tags": ["acip", "cdc", "vaccines", "agendas"], "page_count": 3}
{"title": "final posted 2025 12 04 508", "content": "MEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)    \nAGENDA  \n   \n \nThursday, December 4, 2025   \n   \n8:00 AM    Welcome , Roll Call , and Opening Statement  Dr. Robert Malone  \n(ACIP Vice Chair)      \nDr. Mina Zadeh  \n(ACIP Executive Secretary, CDC)     \n         \n8:30 AM     Hepatitis B  – Recap  Dr. Robert Malone  \n(ACIP Vice Chair)      \n  \n Policy Context and Schedule Comparison   Dr. Vicky Pebsworth   \n(ACIP Childhood and Adolescent \nImmunization Schedule Workgroup \nChair)    \n  \n Burd en of Disease  Dr. Cynthia Nevison  (Presenter )   \n   \n  \n HBV Vaccine Safety  Mr. Mark Blaxill  (CDC )  \n \n   \n Discussion (ACIP members and ex officios)     \n \n Discussion ( Liaisons)   \n \n          \n10:40 AM   Hepatitis B Vaccine  Manufacturers     Dr. Candice Robinson (GSK)  \nDr. Michelle Goveia (Merck)  \nDr. Ayman Chit (Sanofi)     \nQ&A (ACIP members, ex -officios, liaisons)     \n  \n   \n11:05 AM   Lunch   \n \n         \n  \n11:35 AM    Hepatitis B Vaccines  (continued)  \nSummary of the Information and Presentation  \nof the Vo t e Language  Dr. Vicky Pebsworth  \n(ACIP  Childhood and Adolescent \nImmunization  Schedule  Workgroup \nChair)  \nVFC Presentation   Dr. Jeanne Santoli  (CDC ) \nCMS Comments    Mr. Andrew Johnson   \n(CMS , ACIP ex officio ) \nDiscussion (ACIP members and ex officios)   \nDiscussion (Liaisons)  \n1:50 PM Perspectives from People with Lived Experience  \n2:00 PM Public Comments \n2:30 PM  Votes    Dr. Robert Malone (ACIP Vice Chair)  \nHepatitis B Vaccine  \nHepatitis B Vaccine - VFC \n3:15 PM Coverage Implications \nVFC Comments  \nCMS Comments  \n3:25 PM  Break \n3:30 PM  Update on Work Groups      \nDr. Georgina Peacock  (CDC) \nMr. Andrew  Johnson  \n(CMS , ACIP ex officio ) \nDr\n. Robert M alone (ACIP Vi ce Chair)   \n3:35 PM Agency Updates  CDC, CMS, FDA, HRSA, IHS, NIH   \n3:45 PM  Adjourn       \nFriday December 5, 2025   \n         \n8:30 AM     Welcome  and Roll Call     Dr. Robert Malone  \n(ACIP Vice Chair )    \nDr. Mina Zadeh  \n(ACIP Executive Secretary, CDC)    \n  \n   \n9:30 AM   \n  Childhood/Adolescent Immunization Schedule    \nEvolution of the Childhood/Adolescent Vaccination \nSchedule in the U.S. and Vaccine Schedule Comparison: \nU.S. and other Developed Countries  \n     Mr. Aaron Siri  (Presenter )    \n Discussio n (ACIP members and ex officios)     \n      \n Discussion (Liaisons)  \n  \n   \n12:05 PM    Lunch    \n     \n   \n12:35 PM \n U.S. vs. Danish  Vaccine Schedule    Dr. Tracy Beth H oeg  \n(FDA, ACIP e x officio ) \n \n Discussion (ACIP members and ex officios)  \n  \n Discussion (Liaisons)  \n  \n      \n1:35 PM  \n \n Association Between Aluminum Exposure from \nVaccines Before Age 24 Months and Persistent  \nAsthma at Age 24 to 59 Months   \n Dr. Martin Kulldorff  (HHS )  \n Discussion (ACIP members and ex officios)  \n  \n Discussion (Liaisons)  \n  \n   \n2:35 PM     Vaccines and Aluminum  Adjuvants    Dr. Evelyn Griffin  (ACIP Member ) \n  \n Discussion (ACIP members and ex officios)  \n      \n Discussion (Liaisons)  \n    \n   \n3:45 PM    Adjourn", "summary": "MEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)     AGENDA         Thursday, December 4, 2025        8:00 AM    Welcome , Roll Call , and Opening Statement  Dr. Robert Malone   (ACIP Vice Chair)       Dr. Mina Zadeh   (ACIP Executive Secretary, CDC)                8:30 AM     Hepatitis B  – Recap  Dr. Robert Malone   (ACIP Vice Chair)           Policy Context and Schedule Comparison   Dr. Vicky Pebsworth    (ACIP Childhood and Adolescent  Immunization Schedule Workgroup …", "source_url": "https://www.cdc.gov/acip/meetings/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/agendas/final-posted-2025-12-04-508.pdf", "doc_date": "2025-12-04", "case": "acip", "sub_case": "agendas", "tags": ["acip", "cdc", "vaccines", "agendas"], "page_count": 3}
{"title": "draft posted 2025 12 01 508", "content": "MEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)  \nAGENDA - DRAFT  \n \nCe\nnters for Disease Control and Prevention \nAtlanta, Georgia 30329 \n \nThursd ay, December 4, 2025  \n8:00 AM  Welcome and Roll Call   \n   \n Agency Updates   \n    \nHepatitis B Vaccine   \n Presentation   \n Discussion   \n   \n Break   \n   \n Hepatitis B Vaccine  (continued)    \n Presentation   \n Discussion   \n   \n Lunch   \n   \n Hepatitis B Vaccine  (continued)    \n VFC presentation   \n CMS presentation   \n Discussion   \n   \n Public Comments   \n   \n Break   \n   \n Votes  \n   \n5:00 PM  Adjourn     \n \n  \n \nMEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)  \nAGENDA - DRAFT  \n \nCente\nrs for Disease Control and Prevention \nAtlanta, Georgia 30329 \n \nFriday , December 5, 2025     \n9:00 AM Welcome and Roll Call   \n Updates on ACIP Workgroups   \n   \n CDC Vaccine Risk Monitoring Evaluation   \n Discussion   \n   \n Vaccine Schedule History   \n   \n Childhood /Adolescent Immunization Schedule    \n Discussion   \n    \nLunch   \n   \n Vaccine  Schedule  Considerations   \n Discussion   \n   \n Break   \n   \n Adjuvants and Contaminant s  \n Discussion   \n   \n5:30 PM  Adjourn", "summary": "MEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)   AGENDA - DRAFT     Ce nters for Disease Control and Prevention  Atlanta, Georgia 30329    Thursd ay, December 4, 2025   8:00 AM  Welcome and Roll Call         Agency Updates         Hepatitis B Vaccine     Presentation     Discussion         Break         Hepatitis B Vaccine  (continued)      Presentation     Discussion         Lunch         Hepatitis B Vaccine  (continued)      VFC presentation     CMS presentation    …", "source_url": "https://www.cdc.gov/acip/meetings/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/agendas/draft-posted-2025-12-01-508.pdf", "doc_date": "2025-12-01", "case": "acip", "sub_case": "agendas", "tags": ["acip", "cdc", "vaccines", "agendas"], "page_count": 2}
{"title": "draft posted 2025 11 14 508", "content": "MEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)  \nAGENDA - DRAFT  \n \nCe\nnters for Disease Control and Prevention \nAtlanta, Georgia 30329 \n \nThursday, December 4, 2025     \n9:00 AM Welcome and Roll Call   \n Updates on ACIP Workgroups   \n   \n CDC Vaccine Risk Monitoring Evaluation   \n Discussion   \n   \n Vaccine Schedule History   \n   \n Childhood /Adolescent Immunization Schedule    \n Discussion   \n    \nLunch   \n   \n Vaccine  Schedule  Considerations   \n Discussion   \n   \n Break   \n   \n Adjuvants and Contaminant s  \n Discussion   \n   \n5:30 PM  Adjourn   \n  \n \nMEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)   \nAGENDA – DRAFT  \n \nC\nenters for Disease Control and Prevention \nAtlanta, Georgia 30329 \n \nFriday, December 5, 2025  \n8:00 AM  Welcome and Roll Call   \n   \n Agency Updates   \n    \nHepatitis B Vaccine   \n Presentation   \n Discussion   \n   \n Break   \n   \n Hepatitis B Vaccine  (continued)    \n Presentation   \n Discussion   \n   \n Lunch   \n   \n Hepatitis B Vaccine  (continued)    \n VFC presentation   \n CMS presentation   \n Discussion   \n   \n Public Comments   \n   \n Break   \n   \n Votes  \n   \n5:00 PM  Adjourn", "summary": "MEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)   AGENDA - DRAFT     Ce nters for Disease Control and Prevention  Atlanta, Georgia 30329    Thursday, December 4, 2025      9:00 AM Welcome and Roll Call     Updates on ACIP Workgroups         CDC Vaccine Risk Monitoring Evaluation     Discussion         Vaccine Schedule History         Childhood /Adolescent Immunization Schedule      Discussion         Lunch         Vaccine  Schedule  Considerations     Discussion        …", "source_url": "https://www.cdc.gov/acip/meetings/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/agendas/draft-posted-2025-11-14-508.pdf", "doc_date": "2025-11-14", "case": "acip", "sub_case": "agendas", "tags": ["acip", "cdc", "vaccines", "agendas"], "page_count": 2}
{"title": "final posted 2025 09 19 508", "content": "MEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)  \nAgenda \n \nCenters\n for Disease Control and Prevention \nAtlanta, GA  \n \nThursday, September 18, 2025     \n10:00 AM  Welcome and Roll Call  Dr. Martin Kulldorff (ACIP Chair)  \nDr. Mina Zadeh (ACIP Executive Secretary, CDC)     \n10:30 AM  Update on Work Groups  Dr. Martin Kulldorff (ACIP Chair)   \n  \n10:40  AM Measles, Mumps, Rubella, and Varicella \n(MMRV) Vaccines   \n Introduction  Dr. Martin Kulldorff (ACIP Chair)  \n Background on MMRV  Dr. Arjun Srinivasan (CDC/NCIRD)  \n Presentation on febrile seizure following  \nMMRV vaccine  Dr. John Su (CDC/NCEZID)  \n MMRV  Vaccine Manufacturer Statements  TBD  \n Proposed recommendations  and discussion  Dr. Martin Kulldorff (ACIP Chair)  \n VFC presentation  Dr. Jeanne Santoli (CDC/NCIRD)  \n   \n12:35  PM Lunch      \n1:05 PM Hepatitis B Vaccine   \n Introduction  Dr. Martin Kulldorff (ACIP Chair)  \n Presentation on Hepatitis B Birth Dose \nVaccination  Dr. Adam Langer (CDC/NCHHSTP)  \n Hep B vaccine safety updates  Dr. John Su (CDC/NCEZID)  \n Hep B  Vaccine Manufacturer Statements  TBD  \n Proposed recommendations and discussion  Dr. Martin Kulldorff (ACIP Chair)  \n VFC presentation  Dr. Jeanne Santoli (CDC/NCIRD)  \n   \n3:55 PM Break   \n   \n4:10 PM Agency Updates  CDC, CMS, FDA, HRSA, IHS, NIH   \n  \n4:30 PM  Public Comment   \n   \n5:00 PM  Votes   \n \nMMRV vaccines  Dr. Martin Kulldorff (ACIP Chair)  \n MMRV vaccines - VFC  Dr. Jeanne Santoli (CDC/NCIRD)  \n   \n5:30 PM  Adjourn   \n  \nMEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)  \nAgenda \n \nFriday, September 19, 2025  \n8:30 AM  Welcome and Roll Call  Dr. Martin Kulldorff (ACIP Chair)  \nDr. Mina Zadeh (ACIP Executive Secretary, CDC)  \n   \n8:40 AM  Votes   \n Hepatitis B vaccines  Dr. Martin Kulldorff (ACIP Chair)  \n Hepatitis B vaccines – VFC  Dr. Jeanne Santoli (CDC/NCIRD)  \n   \n9:00 AM Agency Updates  CDC, CMS, FDA, HRSA, IHS, NIH  \n   \n9:10 AM COVID -19 Vaccines   \n Introduction  Dr. Retsef Levi (ACIP WG Chair)  \n COVID -19 epidemiology update  Dr. Arjun Srinivasan (CDC/NCIRD)  \n Updates to 2024 -2025 COVID -19 \nImplementation Considerations  Dr. Arjun Srinivasan (CDC/NCIRD)  \n COVID -19 vaccine effectiveness update  Dr. Arjun Srinivasan (CDC/NCIRD)  \n COVID -19 vaccine safety update  Dr. John Su (CDC/NCEZID)  \n   \n10:10 AM Break   \n   \n10:15 AM COVID -19 Vaccines (continued)   \n Workgroup Safety Uncertainties of mRNA  \nCOVID Vaccines  Dr. Wafik El -Deiry & Dr. Charlotte Kuperwasser \n(COVID -19 Workgroup Member)  \n Genomics of Vaccine -Induced Myocarditis  Dr. Bruce Carleton (COVID -19 Workgroup Member)  \n Economic analysis of COVID -19 vaccination  Dr. Arjun Srinivasan (CDC/NCIRD) on behalf of the \nUniversity of Michigan  \n COVID -19 Vaccine Manufacturer Statements  TBD  \n   \n11:25 AM Lunch   \n   \n11:45 AM  COVID -19 Vaccines (continued)   \n COVID -19 Discussion Framing  Dr. Retsef Levi (ACIP WG Chair)  \n Presentation on a dditional workgroup \nconsiderations in COVID- 19 vaccination Policy \nand practice  Dr. Stanley Perlman, Dr. Henry Bernstein, Dr. Mitchell \nMiglis (COVID- 19 Workgroup Members)  \n Proposed recommendations and discussion  Dr. Retsef Levi (ACIP WG Chair)  \n   \n1:45 PM Break   \n   \n1:50 PM Public Comment   \n   \n2:20 PM Votes   \n \nCOVID -19 Vaccines  Dr. Retsef Levi (ACIP WG Chair)  \n   \n3:00 PM  Adjourn   \n \nAcronyms  \nCDC Centers for Disease Control and Prevention \nCMS Centers for Medicare & Medicaid Services  \nCOVID-19 Coronavirus disease 2019 \nFDA Food and Drug Administration \nHRSA Health Resources and Services Administration  \nIHS Indian Health Service MMRV Measles, Mumps, Rubella, Varicella Vaccine NCIRD National Center for Immunization & Respiratory Diseases  \nNCEZID National Center for Emerging and Zoonotic Diseases  NCHHSTP National Center for HIV , Viral Hepatitis, STD, and Tuberculosis Prevention NIH National Institutes of Health  \nVFC Vaccines for Children", "summary": "MEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)   Agenda    Centers  for Disease Control and Prevention  Atlanta, GA     Thursday, September 18, 2025      10:00 AM  Welcome and Roll Call  Dr. Martin Kulldorff (ACIP Chair)   Dr. Mina Zadeh (ACIP Executive Secretary, CDC)      10:30 AM  Update on Work Groups  Dr. Martin Kulldorff (ACIP Chair)       10:40  AM Measles, Mumps, Rubella, and Varicella  (MMRV) Vaccines     Introduction  Dr. Martin Kulldorff (ACIP Chair)   …", "source_url": "https://www.cdc.gov/acip/meetings/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/agendas/final-posted-2025-09-19-508.pdf", "doc_date": "2025-09-19", "case": "acip", "sub_case": "agendas", "tags": ["acip", "cdc", "vaccines", "agendas"], "page_count": 3}
{"title": "final posted 2025 09 18 508", "content": "MEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)  \nAgenda \n \nCent\ners for Disease Control and Prevention \nAtlanta, GA  \n \nThursday, September 18, 2025     \n10:00 AM  Welcome and Roll Call  Dr. Martin Kulldorff (ACIP Chair)  \nDr. Mina Zadeh (ACIP Executive Secretary, CDC)     \n10:30 AM  Update on Work Groups  Dr. Martin Kulldorff (ACIP Chair)   \n  \n10:40  AM Measles, Mumps, Rubella, and Varicella \n(MMRV) Vaccines   \n Introduction  Dr. Martin Kulldorff (ACIP Chair)  \n Background on MMRV  Dr. Arjun Srinivasan (CDC/NCIRD)  \n Presentation on febrile seizure following  \nMMRV vaccine  Dr. John Su (CDC/NCEZID)  \n MMRV  Vaccine Manufacturer Statements  TBD  \n Proposed recommendations  and discussion  Dr. Martin Kulldorff (ACIP Chair)  \n VFC presentation  Dr. Jeanne Santoli (CDC/NCIRD)  \n   \n12:35  PM Lunch      \n1:05 PM Hepatitis B Vaccine   \n Introduction  Dr. Martin Kulldorff (ACIP Chair)  \n Presentation on Hepatitis B Birth Dose \nVaccination  Dr. Adam Langer (CDC/NCHHSTP)  \n Hep B vaccine safety updates  Dr. John Su (CDC/NCEZID)  \n Hep B  Vaccine Manufacturer Statements  TBD  \n Proposed recommendations and discussion  Dr. Martin Kulldorff (ACIP Chair)  \n VFC presentation  Dr. Jeanne Santoli (CDC/NCIRD)  \n   \n3:55 PM Break   \n   \n4:10 PM Agency Updates  CDC, CMS, FDA, HRSA, IHS, NIH   \n  \n4:30 PM  Public Comment   \n   \n5:00 PM  Votes   \n \nMMRV vaccines  Dr. Martin Kulldorff (ACIP Chair)  \n MMRV vaccines - VFC  Dr. Jeanne Santoli (CDC/NCIRD)   \nHepatitis B vaccines  Dr. Martin Kulldorff (ACIP Chair)  \n Hepatitis B vaccines – VFC  Dr. Jeanne Santoli (CDC/NCIRD)  \n   \n5:30 PM  Adjourn   \n  \nMEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)  \nAgenda \n \nFriday, September 19, 2025  \n8:30 AM  Welcome and Roll Call  Dr. Martin Kulldorff (ACIP Chair)  \nDr. Mina Zadeh (ACIP Executive Secretary, CDC)  \n   \n8:40 AM COVID -19 Vaccines   \n Introduction  Dr. Retsef Levi (ACIP WG Chair)  \n COVID -19 epidemiology update  Dr. Arjun Srinivasan (CDC/NCIRD)  \n Updates to 2024 -2025 COVID -19 \nImplementation Considerations  Dr. Arjun Srinivasan (CDC/NCIRD)  \n COVID -19 vaccine effectiveness update  Dr. Arjun Srinivasan (CDC/NCIRD)  \n COVID -19 vaccine safety update  Dr. John Su (CDC/NCEZID)  \n   \n10:05 AM  Break   \n   \n10:10 AM  COVID -19 Vaccines (continued)   \n Workgroup Safety Uncertainties of mRNA  \nCOVID Vaccines  Dr. Wafik El -Deiry & Dr. Charlotte Kuperwasser \n(COVID -19 Workgroup Member)  \n Genomics of Vaccine -Induced Myocarditis  Dr. Bruce Carleton (COVID -19 Workgroup Member)  \n Economic analysis of COVID -19 vaccination  Dr. Arjun Srinivasan (CDC/NCIRD) on behalf of the \nUniversity of Michigan  \n COVID -19 Vaccine Manufacturer Statements  TBD  \n   \n11:40 AM  Lunch   \n   \n12:00 PM  COVID -19 Vaccines (continued)   \n COVID -19 Discussion Framing  Dr. Retsef Levi (ACIP WG Chair)  \nProposed recommendations and discussion  Dr. Retsef Levi (ACIP WG Chair)  \n   \n1:40 PM  Break   \n   \n1:45 PM  Public Comment   \n   \n2:15 PM  Votes   \n \nCOVID -19 Vaccines  Dr. Retsef Levi (ACIP WG Chair)  \n   \n3:00 PM  Adjourn   \n \n  \nAcronyms  \nCDC Centers for Disease Control and Prevention \nCMS Centers for Medicare & Medicaid Services  \nCOVID-19 Coronavirus disease 2019 \nFDA Food and Drug Administration \nHRSA Health Resources and Services Administration  \nIHS Indian Health Service MMRV Measles, Mumps, Rubella, Varicella Vaccine NCIRD National Center for Immunization & Respiratory Diseases  \nNCEZID National Center for Emerging and Zoonotic Diseases  NCHHSTP National Center for HIV , Viral Hepatitis, STD, and Tuberculosis Prevention NIH National Institutes of Health  \nVFC Vaccines for Children", "summary": "MEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)   Agenda    Cent ers for Disease Control and Prevention  Atlanta, GA     Thursday, September 18, 2025      10:00 AM  Welcome and Roll Call  Dr. Martin Kulldorff (ACIP Chair)   Dr. Mina Zadeh (ACIP Executive Secretary, CDC)      10:30 AM  Update on Work Groups  Dr. Martin Kulldorff (ACIP Chair)       10:40  AM Measles, Mumps, Rubella, and Varicella  (MMRV) Vaccines     Introduction  Dr. Martin Kulldorff (ACIP Chair)   …", "source_url": "https://www.cdc.gov/acip/meetings/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/agendas/final-posted-2025-09-18-508.pdf", "doc_date": "2025-09-18", "case": "acip", "sub_case": "agendas", "tags": ["acip", "cdc", "vaccines", "agendas"], "page_count": 3}
{"title": "final posted 2025 09 17 508", "content": "MEETING OF THE ADVISORY COMMITTEE ON IMMUNIZA TION PRACTICES \n(ACIP) Agenda (Final)  \nCenters for Disease Cont rol and Prevention  \nAtlanta, GA \nThursday, September 18, 2025  \n10:00 AM  Welcome and Roll Call  Dr. Martin Kulldorff (ACIP Chair)  \nDr. Mina Zadeh (ACIP Executive Secretary, CDC)   \n10:30 AM  Update on Work Groups  Dr. Martin Kulldorff (ACIP Chair) \n10:40  AM Measles, Mumps, Rubella, and Varicella \n(MMRV) Vaccines  \nIntroduction  Dr. Martin Kulldorff (ACIP Chair)  \nBackground on MMRV  Dr. Arjun Srinivasan (CDC/NCIRD)  \nPresentation on febrile seizure following  \nMMRV vaccine  Dr. John Su (CDC/NCEZID)  \nMMRV  Vaccine Manufacturer Statements  TBD  \nProposed recommendations  and discussion  Dr. Martin Kulldorff (ACIP Chair)  \n12:35  PM Lunch  \n1:05 PM Hepatitis B Vaccine  \nIntroduction  Dr. Martin Kulldorff (ACIP Chair)  \nPresentation on Hep atitis  B Birth Dose \nVaccination  Dr. Adam Langer  (CDC/NCHHSTP)  \nHep B vaccine safety updates  Dr. John Su (CDC/NCEZID)  \nHep B  Vaccine Manufacturer Statements  TBD  \nProposed recommendations  and discussion  Dr. Martin Kulldorff (ACIP Chair)  \n3:55 PM Break  \n4:10 PM Agency Updates  CDC, CMS, FDA, HRSA, IHS, NIH  \n4:30 PM Public Comment  \n5:00 PM Votes  \nMMRV vaccines  Dr. Martin Kulldorff (ACIP Chair) \nMMRV vaccines - VFC  Dr. Jeanne Santoli (CDC/NCIRD)  \nHepatitis B vaccines  Dr. Martin Kulldorff (ACIP Chair) \nHepatitis B vaccines – VFC  Dr. Jeanne Santoli (CDC/NCIRD)  \n5:30 PM  Adjourn  \nMEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)  \nAgenda (Draft)  \n \nFriday, September 19, 2025  \n8:30 AM  Welcome and Roll Call  Dr. Martin Kulldorff (ACIP Chair)  \nDr. Mina Zadeh (ACIP Executive Secretary, CDC)  \n   \n8:40 AM COVID -19 Vaccines   \n Introduction  Dr. Retsef Levi (ACIP WG Chair)  \n COVID -19 epidemiology update  Dr. Arjun Srinivasan (CDC/NCIRD)  \n Updates to 2024 -2025 COVID -19 \nImplementation Considerations  Dr. Arjun Srinivasan (CDC/NCIRD)  \n COVID -19 vaccine effectiveness update  Dr. Arjun Srinivasan (CDC/NCIRD)  \n COVID -19 vaccine safety update  Dr. John Su (CDC/NCEZID)  \n   \n10:05 AM  Break   \n   \n10:10 AM  COVID -19 Vaccines (continued)   \n Workgroup Safety Uncertainties of mRNA  \nCOVID Vaccines  Dr. Wafik El -Deiry  & Dr. Charlotte Kuperwasser \n(COVID -19 Workgroup Member)  \n Genomics of Vaccine -Induced Myocarditis  Dr. Bruce Charleton (COVID -19 Workgroup Member)  \n Economic analysis of COVID -19 vaccination  Dr. Arjun Srinivasan (CDC/NCIRD) on behalf of the \nUniversity of Michigan  \n COVID -19 Vaccine Manufacturer Statements  TBD  \n   \n11:40 AM  Lunch   \n   \n12:00 PM  COVID -19 Vaccines (continued)   \n COVID -19 Discussion Framing  Dr. Retsef Levi (ACIP WG Chair)  \nProposed recommendations and discussion  Dr. Retsef Levi (ACIP WG Chair)  \n   \n1:40 PM  Break   \n   \n1:45 PM  Public Comment   \n   \n2:15 PM  Votes   \n \nCOVID -19 Vaccines  Dr. Retsef Levi (ACIP WG Chair)  \n   \n3:00 PM  Adjourn   \n \n  \nAcronyms  \nCDC Centers for Disease Control and Prevention  \nCMS Centers for Medicare & Medicaid Services  \nCOVID -19 Coronavirus disease 2019  \nFDA Food and Drug Administration  \nHRSA Health Resources and Services Administration  \nIHS Indian Health Service  \nMMRV Measles, Mumps, Rubella, Varicella Vaccine  \nNCIRD National Center for Immunization & Respiratory Diseases  \nNCEZID National Center for Emerging and Zoonotic Diseases  \nNCHHSTP National Center for HIV , Viral Hepatitis, STD, and Tuberculosis Prevention  \nNIH National Institutes of Health  \nVFC Vaccines for Children", "summary": "MEETING OF THE ADVISORY COMMITTEE ON IMMUNIZA TION PRACTICES  (ACIP) Agenda (Final)   Centers for Disease Cont rol and Prevention   Atlanta, GA  Thursday, September 18, 2025   10:00 AM  Welcome and Roll Call  Dr. Martin Kulldorff (ACIP Chair)   Dr. Mina Zadeh (ACIP Executive Secretary, CDC)    10:30 AM  Update on Work Groups  Dr. Martin Kulldorff (ACIP Chair)  10:40  AM Measles, Mumps, Rubella, and Varicella  (MMRV) Vaccines   Introduction  Dr. Martin Kulldorff (ACIP Chair)   Background on…", "source_url": "https://www.cdc.gov/acip/meetings/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/agendas/final-posted-2025-09-17-508.pdf", "doc_date": "2025-09-17", "case": "acip", "sub_case": "agendas", "tags": ["acip", "cdc", "vaccines", "agendas"], "page_count": 3}
{"title": "draft posted 2025 09 12 508", "content": "MEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)  \nAgenda (Draft) \n \nCenters for D\nisease Con trol and Prevention \nAtlanta, GA  \n \nThursday, September 18, 2025     \n10:00 AM  Welcome and Roll Call  Dr. Martin Kulldorff (ACIP Chair)  \nDr. Mina Zadeh (ACIP Executive Secretary, CDC)     \n10:30 AM  Update on Work Groups  Dr. Martin Kulldorff (ACIP Chair)   \n  \n11:00 AM  Measles, Mumps, Rubella, and Varicella \n(MMRV) Vaccines   \n Introduction  Dr. Martin Kulldorff (ACIP Chair)  \n Background on MMRV  Dr. Arjun Srinivasan (CDC/NCIRD)  \n Presentation on febrile seizure following  \nMMRV vaccine  Dr. John Su (CDC/NCEZID)  \n Proposed recommendations  and discussion  Dr. Martin Kulldorff (ACIP Chair)  \n   \n1:00 PM  Lunch      \n1:30 PM Hepatitis B Vaccine   \n Introduction  Dr. Martin Kulldorff (ACIP Chair)  \n Presentation on Hep atitis  B Birth Dose \nVaccination  Dr. Adam Langer  (CDC/NCHHSTP)  \n Hep B vaccine safety updates  Dr. John Su (CDC/NCEZID)  \n Proposed recommendations  and discussion  Dr. Martin Kulldorff (ACIP Chair)  \n   \n4:00 PM Break   \n   \n4:15 PM Agency Updates  CDC, CMS, FDA, HRSA, IHS, NIH   \n  \n4:30 PM Public Comment   \n   \n5:00 PM Votes   \n \nMMRV vaccines  Dr. Martin Kulldorff (ACIP Chair)  \n MMRV vaccines - VFC  Dr. Jeanne Santoli (CDC/NCIRD)   \nHepatitis B vaccines  Dr. Martin Kulldorff (ACIP Chair)  \n Hepatitis B vaccines – VFC  Dr. Jeanne Santoli (CDC/NCIRD)  \n   \n5:30 PM  Adjourn   \n  \nMEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)  \nAgenda (Draft) \n \nFriday, September 19, 2025  \n8:30 AM  Welcome and Roll Call  Dr. Martin Kulldorff (ACIP Chair)  \nDr. Mina Zadeh (ACIP Executive Secretary, CDC)  \n   \n8:45 AM  COVID -19 Vaccines   \n Introduction  Dr. Retsef Levi (ACIP WG Chair)  \n COVID -19 epidemiology update  Dr. Arjun Srinivasan (CDC/NCIRD)  \n Updates to 2024 -2025 COVID -19 Implementation \nConsiderations  Dr. Arjun Srinivasan (CDC/NCIRD)  \n COVID -19 vaccine effectiveness update  Dr. Arjun Srinivasan (CDC/NCIRD)  \n COVID -19 vaccine safety update  Dr. John Su (CDC/NCEZID)  \n Additional COVID -19 vaccine safety  presentations   TBD  \n   \n11:30  AM Lunch   \n   \n12:00 PM COVID -19 Vaccines (continued)   \n Economic analysis of COVID -19 vaccination  Dr. Arjun Srinivasan (CDC/NCIRD) on behalf of \nthe University of Michigan  \n COVID -19 Vaccine Manufacturer update s TBD  \n COVID -19 Discussion Framing  Dr. Retsef Levi (ACIP WG Chair)  \nProposed recommendations  and discussion  Dr. Retsef Levi (ACIP WG Chair)  \n   \n1:40 PM  Break   \n   \n1:45 PM  Public Comment   \n   \n2:15 PM  Votes   \n \nCOVID -19 Vaccines  Dr. Retsef Levi (ACIP WG Chair)  \n   \n3:00 PM  Adjourn", "summary": "MEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)   Agenda (Draft)    Centers for D isease Con trol and Prevention  Atlanta, GA     Thursday, September 18, 2025      10:00 AM  Welcome and Roll Call  Dr. Martin Kulldorff (ACIP Chair)   Dr. Mina Zadeh (ACIP Executive Secretary, CDC)      10:30 AM  Update on Work Groups  Dr. Martin Kulldorff (ACIP Chair)       11:00 AM  Measles, Mumps, Rubella, and Varicella  (MMRV) Vaccines     Introduction  Dr. Martin Kulldorff (ACIP Chair)   …", "source_url": "https://www.cdc.gov/acip/meetings/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/agendas/draft-posted-2025-09-12-508.pdf", "doc_date": "2025-09-12", "case": "acip", "sub_case": "agendas", "tags": ["acip", "cdc", "vaccines", "agendas"], "page_count": 2}
{"title": "summary 2025 9 18 19 508", "content": "MEETING OF THE ADVISORY \nCOMMITTEE ON IMMUNIZATION \nPRACTICES (ACIP)  \n \nSEPTEMBER  18-19, 2025  \nMEETING SUMMARY  \n \n \n \n \n \n  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nTrade names are used for identification purposes only and do not indicate endorsement.  \n \n \n \n \n2 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  THURSDAY : SEPTEMBER 18, 202 5 \n \nWELCOME AND ROLL CALL  \n \nCall to Order/Roll Call  \n \nDr. Mina Zadeh, ACIP Executive Secretary, CDC, convened the meeting at 10:00 a.m. on \nSeptember 18, 2025, and welcomed participants to the September 18– 19 session of the \nAdvisory Committee on Immunization Practices (ACIP). She provided general logistical information and noted that presentation slides were available on the ACIP website. Dr. Zadeh \nreviewed the public comment process, explaining that two oral comment sessions were \nscheduled, with 19 speakers selected in advance through a blinded lottery, and that written \ncomments were accepted through regulations.gov (Docket No. CDC -2025 -0454). She \nreaffirmed ACIP’s commitment to transparency and reviewed conflict of interest policies, noting that members must disclose relevant conflicts and may receive limited waivers for activities that \nenhance expertise but may not vote on related matters.  \n \nDr. Zadeh then conducted the roll call and introduced five new ACIP members appointed for the September 2025 meeting: Dr. Catherine M. Stein, Dr. Evelyn Griffin, Dr. Hilary Blackburn, Dr. \nKirk Milhoan, and Dr. Raymond Pollak. A complete list of Members, Ex  Officio members, and \nLiaison Representatives is provided in the appendices at the end of this summary document.  \nWhile no conflicts of interest were identified for the first day of the meeting, Dr. Robert Malone \nabstained from the MMRV votes due to existing legal agreements.  \n \nUPDATE ON WORK GROUPS  \n \nDr. Kulldorff provided an update on the  current  work group s, noting that several are actively \nengaged in ongoing scientific discussions and analyses, with some scheduled to present their \ndeliberations during this session. He announced the formation of two new work groups: one \nfocused on vaccines in pregnant women  and another on the childhood and adolescent vaccine \nschedule.  \n \nHe explained that most existing work groups focus on individual vaccines or related vaccine groups . The new group will  examine interaction effects and optimal sequencing within the \nbroader vaccine schedule. Dr. Kulldorff emphasized the importance of careful consideration when evaluating vaccines during pregnancy due to potential risks, such as birth defects. He \nconcluded by noting that findings from these new work groups will be presented at future ACIP \nmeetings.  \n \nMEASLES, MUMPS, RUBELLA, AND VARICELLA  (MMRV) VACCINE  \n \nIntroduction  \nDr. Martin Kulldorff (ACIP Chair)  \nDr. Martin Kulldorff, Chair of the ACIP, opened the session by introducing the MMRV (measles, mumps, rubella, varicella) vaccine. He noted that the vaccine combines protection against four \ndiseases in a single injection, developed to replace two separate shots (MMR and varicella), \nthereby reducing the number of needles children receive.  \n \n3 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  Background on MMRV  \nDr. Arjun Srinivasan (CDC/NCIRD)  \nDr. Arjun Srinivasan (CDC/NCIRD) provided background information on the measles, mumps, \nrubella, and varicella (MMRV) vaccine. He reviewed the significant health burden of these \ndiseases in the United States (U.S.) before vaccine introduction. During the 1964 to 1965 \nrubella epidemic, approximately 11,000 pregnant women lost their babies, 2,100 newborns died, \nand 20,000 were born with congenital rubella syndrome, which can cause deafness, heart \ndefects, and developmental delays. Before the measles vaccine, an estimated 48,000 \nhospitalizations and 400 to 500 deaths occurred each year due to measles. Mumps was the \nleading cause of viral encephalitis and sudden -onset deafness before the introduction of \nvaccination. In the early 1990s, varicella caused between 10,500 and 13,500 hospitalizations \nannually, along with 100 to 150 deaths.  \n The introduction of vaccines to protect against these diseases, in the form of monovalent \nvaccines and combination vaccines such as MMR (measles, mumps, rubella) and MMRV \n(measles, mumps, rubella, varicella), coupled with achieving and maintaining coverage  rates \nabove 90%, led to dramatic reductions in disease burden in the U.S. These efforts resulted in the elimination of endemic measles in 2000, elimination of endemic rubella in 2004, a 99% \ndecline in mump cases by the early 2000s, and a 97% decline in va ricella incidence by 2019.  \n \nIn the U.S., two options are available for measles, mumps, rubella, and varicella vaccination: the \ncombination MMRV vaccine or MMR plus varicella vaccine. The routine schedule consists of \ntwo doses, administered at 12– 15 months and 4– 6 years. The MMRV vacc ine available in the \nUS, ProQuad, manufactured by Merck, was licensed by the FDA in September 2005 based on \nthe non -inferior immunogenicity of its components compared with the simultaneous \nadministration of the MMR and varicella vaccines. Efficacy of the i ndividual components had \nalready been established in clinical studies of the monovalent vaccines. At the time of  MMRV  \nlicensure, disease burden in the U.S. was too low to perform efficacy -based clinical trials for the \nMMRV vaccine , so immunobridging trials were used to support approval.  [Of note, \nimmunobridging trials is an established approach for the development of vaccines. ]  \n \nImmunogenicity after the first dose of MMRV was compared with that of MMR plus varicella \nvaccine in children aged 12– 23 months in four randomized clinical trials. A total of 5,446 \nchildren received MMRV and 238 received MMR plus varicella at separate injec tion sites. In \nthese studies, seroconversion rates and geometric mean titers were similar between groups and met the pre -established criteria for non -inferiority. Immunogenicity after the second dose in \nchildren aged 4– 6 years was assessed in one randomized clinical trial, where 399 children \nreceived MMRV, 205 received MMR plus placebo, and 195 received MMR plus varicella. The \nfindings also met the pre -established criteria for non- inferiority. As noted in the 2008 and 2009 \nreviews by the ACIP Vaccine Work G roup, safety after MMRV was compared with MMR plus \nvaricella. Based on the demonstrated non- inferior immunogenicity, vaccine effectiveness was \nassumed to be equal.  \n \nUpon licensure in September 2005 for children aged 12 months t hrough  12 years, MMRV was \npreferred over the separate administration of MMR and varicella vaccines, consistent with the \nACIP’s preference at the time for combination vaccines. In February 2008, preliminary post -\nlicensure safety findings from two studies identifi ed an increased risk of febrile seizures after the \nfirst dose of MMRV, leading ACIP to remove its preference for MMRV over separate \nadministration of MMR and varicella for both the first and second doses. After further review of \nsafety data, consideration of the benefits of one fewer injection with MMRV, analysis of febrile \n4 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  seizure epidemiology, input from parents and providers, and consultation with ethics experts, \nthe ACIP issued updated recommendations in June 2009.  \n These recommendations remain current and state that for the first dose of measles, mumps, \nrubella, and varicella vaccination at age 12– 47 months, either MMR plus varicella or MMRV \nmay be used. Providers who consider administering MMRV should discuss the benefits and \nrisks of both options with parents and caregivers. At the time of publication, CDC \nimplementation guidance recommended that, unless a parent or caregiver specifically preferred \nMMRV, the first dose in this age group should be administered as separate MMR and varicella \nvaccines. For the first dose at age 48 months or older and for the second dose at any age \nthrough 12 years, MMRV is generally preferred over separate administration of MMR and \nvaricella vaccines.  \n \nNo post -licensure vaccine effectiveness estimates are available for MMRV used  in the U.S., as \nmeasles and rubella have been eliminated, and mumps and varicella remain at very low levels. \nThere are not enough cases or outbreaks among children in the U.S. to assess vaccine \neffectiveness. However, those vaccinated with either MMRV or MMR plus varicella continue to \nhave very low rates of measles, mumps, rubella, and varicella. To date, CDC has received no \nreports suggesting lower effectiveness of MMRV compared with the separate component \nvaccines, consistent with the immunogenicity resu lts observed in clinical trials.  \n In terms of utilization, MMRV accounts for 15% of first -dose measles, mumps, rubella, and \nvaricella vaccination among children aged 19– 35 months. In most states, the use of MMRV for \nthe first dose ranges from about 10% to under 20%, based on the first and third quartiles. Among children aged 4– 6 years, MMRV accounts for 75% of second- dose vaccination.  \n Dr. Srinivasan concluded that the MMRV vaccine is one of two options for vaccination of U.S. \nchildren against measles, mumps, rubella, and varicella. As ACIP assessed in 2008 and 2009, \ngiven the balance of risks and benefits of a first dose of MMRV compared with a first dose of \nMMR plus varicella, and the importance of individual values and preferences in weighing these \nrisks and benefits , maximizing choice remains an important ethical principle. Decisions should \nbe made on a case -by-case basis by providers , parents, or caregivers. The two vaccination \noptions, MMRV or separate injections of MMR and varicella, are considered equivalent in terms \nof protection. Under current recommendations, most MMRV use in the U.S. is among children \naged 4– 6 years for the sec ond dose. Overall, vaccination for measles, mumps, rubella, and \nvaricella has resulted in a reduction of at least 97% in all four diseases compared to the pre -\nvaccine era.  \n \nDiscussion  \n Dr. Milhoan requested clarification on the adjuvant content, specifically comparing the amount in \nthe MMRV vaccine with that of administering MMR and varicella separately, and whether the \nadjuvant is similar or different between these options.  \nDr. Oliver, NCIRD SME, clarified that neither the MMRV vaccine nor the separately administered MMR plus varicella vaccines contain an adjuvant.  \n \nDr. Hibbeln  inquired about the overall risk -benefit balance, noting that the benefits were \ndescribed extensively and that febrile seizures were identified as a potential risk. He requested \nan assessment of the magnitude of harm from febrile seizures and other side ef fects in relation \nto the benefits at both the individual and population levels.  \n \n5 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  Dr. Srinivasan stated that Dr. Su would present the risk profile in the following presentation.  \n \nDr. Malone disclosed that, due to his prior service as an expert witness in litigation involving \nvaccines, which granted him access to internal manufacturer communications under a legal \nagreement, he is bound not to conduct research on or offer opinions about these products. He \nclarified that he will not vote on this topic and has no opinion to provide due to the pre -existing \nlegal agreement.  \n \nDr. Pebsworth requested clarification on the varicella antigen amount in the two vaccination \noptions: MMRV versus separate MMR plus varicella, and whether the amounts differ.  \n \nDr. Marin, NCIRD SME, clarified that the measles, mumps, and rubella components are the \nsame in MMR and MMRV. The varicella component in MMRV utilizes the same virus strain as \nthe single- antigen varicella vaccine, but at a higher potency, approximately 3.99 log10 PFU, \ncompared to about 3.13 log10 PFU in the single- antigen product, or roughly sevenfold higher. \nThe viruses themselves are identical across products; the difference is potency.  \n \nDr. Levi asked whether there is a biological or clinical rationale for the higher varicella antigen \namount in MMRV compared with separate administration of MMR plus varicella, and why more \nis needed when included in the combination vaccine.  \n Dr. Marin explained that initial manufacturer trials using the same varicella potency as the \nsingle -antigen vaccine within MMRV produced a suboptimal immunologic response to the \nvaricella component. Manufacturers then tested higher varicella potencies and selected the \ncurrent formulation as the best balance of immunogenicity and adverse events. Evidence \nreviewed in 2008– 2009 suggested potential interference between the measles and varicella \nviruses when combined in the same vaccine, resulting in a stronger measles response (with \nmore fever and a measles -like rash) and a weaker varicella response than with a single- antigen \nvaricella vaccine. Increasing the varicella potency in MMRV was intended to achieve an immune \nresponse comparable to that of the single- antigen varicella vaccine.  \n \nDr. Levi asked whether there is a clearly understood biological mechanism that explains why \ndifferent vaccine formulations and combinations produce different immune responses, beyond \nthe outcomes observed.  \n Dr. Kulldorff shared that the manufacturer will provide more information on this topic later in the \nmeeting.  \n \nDr. Blackburn requested clarification on immunogenicity following the first dose of the MMR \nvaccine. She noted that most children develop protective antibodies after the initial dose and \nasked for the scientific basis for recommending a routine second dose. She wondered whether \nthe second dose primarily addresses primary vaccine failure, waning immunity, or both, and \nwhether antibody titers could be used to verify response after the first dose, rather than \nuniversally administering a second dose.  \n \nDr. Oliver stated that antibody titers are one component of the protective response and are \nhigher after two doses. She noted that the second dose, particularly for measles, helps identify \nand protect children who did not mount a protective response to the first dose, addressing \nprimary vaccine failure. Two doses are recommended because this schedule has been used in \nmany efficacy studies and provides additional overall protection.  \n \n6 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  Dr. Blackburn requested percentages.  \n \nDr. Oliver referenced slide 15 in the presentation, which showed seropositivity rates, percent \nfold rise in antibody titers, and geometric mean titers across multiple doses for ProQuad \n(MMRV), with MMR plus Varivax shown at the bottom of each group as the separate- vaccine \ncomparator.  \n Dr. Milhoan inquired whether data are available on the serologic response after the primary first \ndose, noting that the presented results reflect responses after the second dose, and requested \nseroconversion or seropositivity data following the first dose.  \n \nDr. Oliver shared that the data can be found on slide 13.  \n \nDr. Meissner emphasized that while recent attention has focused on measles vaccination, \nrubella vaccination is equally critical. He noted that the last rubella pandemic in the U.S. \noccurred in 1964– 1965, resulting in approximately 11,000 fetal deaths and 20,000 infants born \nwith congenital rubella syndrome, a severe condition associated with congenital heart disease, developmental delay, and eye problems. He added that in 1969, Dr. Stanley Plotkin and \ncolleagues at the Wistar Institute developed the rubella vaccine, which has been highly \neffective. In recent years, the U.S. has typically seen fewer than five cases of congenital rubella annually, primarily among women born in countries without rubella vaccination programs. He \nunderscored the importance of ens uring every child is vaccinated against measles, mumps, \nrubella, and varicella.  \n Dr. Meissner thanked the chair and expressed appreciation for the participation of professional \nsocieties focused on infectious diseases and vaccines. He stated that the American Academy of Pediatrics’ non- participation in these discussions is a mistake and expressed concern that \ncontinued absence could diminish the Academy’s influence.  \nFebrile Seizures following Measles, Mumps, Rubella, and Varicella (MMRV) vaccine  \nDr. John Su (CDC/NCEZID)  \n Dr. John Su (CDC/NCEZID) presented on febrile seizures following Measles, Mumps, Rubella, \nand Varicella (MMRV) vaccine. The ACIP chair requested that the Immunization Safety Office \npresent an analysis of febrile seizures following the administration of MMR V compared with the \nsimultaneous administration of separate MMR and varicella vaccines, with results stratified by two age groups: 1– 2 and 4 –6 years. The presentation should draw on data from randomized \nclinical trials and from the Vaccine Safety Datalink (VSD) project.  \n Dr. Su recapped that MMRV was licensed in the U.S. in 2005. Interim recommendations in 2008 \nremoved the preferential recommendation for MMRV, and updated recommendations were \nissued in June 2009. Between February 2008 and June 2009, the MMRV Vaccine Safety  Work \nGroup reviewed multiple data sources, including two post -licensure studies from Merck and \nanalyses from the Vaccine Safety Datalink (VSD). In brief, the 2009 updates stated that unless \na parent or caregiver prefers MMRV, the first dose for children aged 12– 47 months should be \nadministered as separate MMR and varicella vaccines, while MMRV remains generally \npreferred for the second dose. Additional details can be found in the May 2010 issue of the \nMMWR Recommendations and Reports.  \n \nBackground on the MMRV vaccine and febrile seizures was provided. Combination vaccines, \nlike MMRV, reduce the number of injections a child receives and can improve vaccine \n7 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  compliance and coverage. MMRV is licensed for children aged 12 months –12 years. The \nroutine schedule recommends two doses: the first at 12– 15 months of age and the second at 4–\n6 years  of age . ProQuad is the MMRV product licensed for use in the U.S.  \n \nFebrile seizures are seizures that occur in children who have a fever. By age 5 years, 2– 4% of \nchildren have had at least one. They occur primarily between 6 months and 5 years  of age, with \na peak between 14 and 18 months of age. Although distressing, most febrile seizures are short (less than 15 minutes) and resolve without complications. They most commonly accompany \nfevers from routine childhood illnesses such as middle ear infections, viral upper respiratory \ninfections, and roseola. Still, they can occur  with any condition that causes fever, including \nthose that follow vaccination. A family history of febrile seizures increases risk.  \n \nPre-licensure studies of MMRV among children aged 12– 23 months found that fever and \nmeasles -like rash were reported significantly more often during the 0– 42 days after vaccination \nin children who received a first dose of MMRV than in those who received separate first doses \nof MMR and varicella at the same visit. Fever occurred in 21.5% of MMRV recipients versus \n14.9% of recipients of separate MMR and varicella (risk difference 6.6%; 95% CI, 4.6% –8.5%). \nConsidering these findings, CDC and Merck initiated pos t-licensure studies to evaluate whether \nan increased risk of febrile seizures might be associated with the first dose of MMRV.  \n \nAnalyses of postvaccination intervals from a Vaccine Safety Datalink (VSD) study and a Merck -\nsponsored study, conducted primarily among children aged 12– 23 months, used different \npopulations and methods. Yet, both found significant associations in the firs t two weeks after \nvaccination. The VSD study, after medical record review, confirmed an increased risk of febrile \nseizures during days 7– 10 after MMRV compared with MMR plus varicella, with an attributable \nrisk of 4.3 per 10,000 doses and a relative risk o f 2.0 (95% CI, 1. 4–2.9). The Merck -sponsored \nstudy also observed an increased risk during days 5– 12 after MMRV, with an attributable risk of \n1.3 per 10,000 doses administered during 0– 30 days postvaccination; the relative risk was 1.1 \nwith a non -significant confidence interval.  \n \nAn analysis of VSD outpatient visits for fever among children aged 12– 23 months from 2000 to \n2008 revealed that fever visits increased after any measles -containing vaccine during days 7–\n10 postvaccination, with the greatest increase following MMRV. Temporal scan statistics \nidentified significant clustering on days 7– 10 for all measles -containing vaccines (p < 0.001), \nwhile no temporal clustering of fever visits was observed after varicella vaccination alone.  \n \nAn analysis of the number of seizures after vaccination among children aged 12– 23 months \n(2000– 2008) revealed peaks on days 7– 10 following any measles -containing vaccine, with the \nhighest counts occurring after MMRV vaccination. Temporal scan statistics indicated significant clustering on days 8– 10 after MMRV (relative risk 7.6; p=0.001), days 7– 10 after MMR plus \nvaricella given at the same visit (relative risk 4.0; p=0.001), and days 7– 11 after MMR alone \n(relative risk 3.7; p=0.001). No seizure peak or significant temporal clustering was observed \nafter varicella vaccination alone.  \n \nA review of the biomedical literature on post -licensure febrile seizures following MMR or \nvaricella vaccination identified one study showing a significant increase in febrile seizures during \ndays 8– 14 after MMR compared with unvaccinated children, corresponding to approximately \none additional febrile seizure per 3,000– 4,000 children vaccinated. No increased risk of febrile \nseizure was observed among children aged 12– 23 months after varicella vaccination during the \n0–30 days postvaccination.  \n \n8 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  A 2015 systematic review and meta -analysis assessed the risk of febrile seizures following \nMMRV vaccination, including studies that used Priorix Tetra (MMRV) or ProQuad (MMRV). The \nanalysis included both clinical trials and post -marketing observations, wit h some studies \nenrolling children as young as 9 months. Clinical trial data showed no significant differences in \nfebrile seizure incidence between MMRV and MMR, with or without varicella, after any dose \nacross multiple risk windows. Additionally, concomitant administration of MMRV with other pediatric vaccines was not a significant predictor of febrile seizures. In post -marketing analyses, \nan approximate twofold increase in risk of seizure or febrile seizure was observed during days \n7–10 or 5– 12 after MMRV vaccination in children aged 10– 24 months.  \n \nA 2021 Cochrane review examined the use of MMRV in children, including five cohort studies, \nfour of which evaluated first -dose vaccination only. Overall, there was a significant increase in \nfebrile seizure risk among children receiving MMRV compared with s eparate MMR and varicella \nduring the 0– 42 days postvaccination and during days 7– 10. In brand- stratified analyses, a \ncohort study of Priorix Tetra reported non- significant findings for febrile seizure risk compared \nwith separate MMR and varicella vaccines,  including in post hoc analyses. The four other cohort \nstudies, which evaluated ProQuad, showed a significantly increased risk during the 0– 42-day \nand 7– 10-day postvaccination windows.  \n \nDr. Su summarized that post -licensure studies assessed febrile seizures in children aged 12– 23 \nmonths who received a first dose of MMRV compared with children who received a first dose of MMR and varicella at the same visit. Despite differences in methods,  populations  of children, \nand MMRV formulations, the findings were consistent across all studies. Studies identified an \nincreased risk of febrile seizures during the 1– 2 weeks after the first dose of MMRV compared \nwith the first dose of MMR plus varicella;  outside that period, risks were similar between the two \noptions.  \n MMRV is licensed as a two- dose series, with the routine second dose at ages 4– 6 years. The \nrisk of febrile seizures is lower in children aged 4– 6 years than in those aged 12– 15 months. In \nMerck pre -licensure trials, fever rates were lower after a second dose of MMRV in children aged \n15–31 months than after the first dose. Among children aged 4– 6 years, fever rates were similar \nafter receiving a second dose of MMRV and after receiving a second dose of MMR plus varicella, both administered at the same visit.  \n \nMerck -sponsored studies among children aged 4 –6 years observed no febrile seizures in either \nof the comparison arms. In a VSD post -licensure study, very few seizures were identified by \nICD-9 codes after measles -containing vaccines, with no significant diff erences during days 7 –10 \nor 0– 42 after MMRV, MMR plus varicella, or MMR alone. However, rates were numerically \nhigher after MMRV. Electronic medical record review of the four events coded as seizures, 7– 10 \ndays after MMRV, found two afebrile seizures, one indeterminate event, and one confirmed \nfebrile seizure. The resulting occurrence  of febrile seizure 7– 10 days after a second dose of \nMMRV was 1 per 86,750 doses (about 1.2 per 100,000), with the upper 95% confidence limit corresponding to no more than 1 per 15,570 doses (about 6.4 per 100,000). Similarly, for MMR \nplus varicella given the same day, the upper 95% confidence limit corresponded to no more \nthan one febrile seizure per 18,282 doses.  \n The systematic review published in 2015 examined febrile seizure incidence and risk after the \nsecond MMRV dose. Pre -licensure data showed no statistically significant differences between \nchildren who received MMRV alone and those who received MMRV with one or more other \npediatric vaccines at the same visit. Likewise, there were no significant differences between children who received MMRV plus other pediatric vaccines and those who received other \n9 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  pediatric vaccines without MMRV. The systematic review also summarized a post -licensure \nVSD study concluding that, among children aged 4– 6 years, neither MMRV nor same -day \nseparate MMR and varicella vaccination was associated with an increased risk of febr ile \nseizures.  \n \nDr. Su summarized that among children aged 4– 6 years, the data do not suggest an increased \nrisk of febrile seizures after a second dose of MMRV compared with a second dose of MMR \nplus varicella given at the same visit. In conclusion, there is a small increased risk of febrile \nseizures after the first dose of measles -containing vaccines (MMR and MMRV), with the risk \nslightly higher after MMRV. Studies have shown a small increased risk during days 5– 12 after \nthe first MMR dose; no increased risk has been observed after the varicella vaccine alone. \nThere is no increased risk of febrile seizures after MMRV in children aged 4– 6 years.  \n \nDiscussion  \n \nDr. Kulldorff asked whether vaccine coverage rates are influenced more by the reduced number \nof injections with combination vaccines or by concerns arising from adverse reactions that may \nspread through families and communities. He requested studies that quantify both effects and \nindicate which has the greater impact on coverage.  \n Dr. Srinivasan acknowledged the question, noted that subject matter experts could better \naddress the effects of vaccine coverage, and requested the backup slide on the parent and \nprovider survey to inform the discussion.  \n \nDr. Oliver reported that the National Immunization Survey Child COVID module, published in \n2024, asked parents to consider routine childhood vaccines (measles, polio, tetanus) and \nindicate overall hesitancy. Only 14% of parents of children aged 6 months –4 years expressed \nhesitancy toward these routine vaccines.  \n Dr. Kulldorff asked whether the 14% hesitancy figure referred specifically to parents whose child \nhad experienced a febrile seizure or to the broader survey population.  \n \nDr. Oliver clarified that the 2024 National Immunization Survey Child COVID module was a \nrandom -digit-dial survey of the general parent population, not specifically parents of children \nwho had experienced febrile seizures.  \n \nDr. Kulldorff asked how a febrile seizure attributed to MMRV, compared with MMR plus \nvaricella, affects parents’ willingness to continue vaccinating the child, vaccinate younger \nsiblings, and recommend vaccination within their social circles. He asked whet her such events \nreduce coverage and whether any studies quantify these effects relative to the coverage gains from fewer injections with combination vaccines, and which effect is larger.  \n \nDr. Oliver referenced background slide 27 from the MMRV presentation and noted that there are \nno survey data specifically of parents whose children previously had febrile seizures. She \nexplained that during the 2008– 2009 Work Group discussions, a parent su rvey of mothers \nfound that approximately 33% would be resistant to MMRV, about 25% were neutral, and \naround 40% would accept it. She emphasized that the most effective conversations about \nvaccination risks and side effects occur between the pediatrician and the parent, and that \nparents should be offered a choice between MMRV and separate MMR plus varicella. The CDC \nrecommends that pediatricians include these risks in counseling and help families weigh the \nbenefits and risks for the specific child and situat ion. \n10 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.   \nDr. Kulldorff acknowledged that there are no data available and that it is difficult to quantify how \nmuch vaccine hesitancy might increase because of additional febrile seizures.  \n \nDr. Meissner noted that the discussion mirrors debate from about 15 years ago and was one of \nthe few times the ACIP and the American Academy of Pediatrics (AAP) diverged, with the AAP not expressing a preference for the 12– 15 months dose, while the ACIP al lowed the use of \nseparate MMR plus varicella. He added that a busy pediatric practice might see about one \nadditional febrile seizure after MMRV at 12– 15 months compared with separate vaccines. He \nasked Drs. Su and Oliver to confirm that febrile seizures af ter MMR alone at 12– 15 months \noccur at roughly 1 per 3,000 doses and that MMRV increases the risk about twofold.  \n \nDr. Su confirmed that prior studies show an additional risk of about one febrile seizure per \n3,000– 4,000 children after MMR and that a twofold increase in risk with MMRV compared with \nseparate MMR plus varicella is correct.  \nDr. Meissner asked to confirm that more than 95% of febrile seizures occur before age 4, with \nonly a small percentage occurring after age four from any cause.  \n \nDr. Su noted that febrile seizures after age five are rare.  \n Dr. Levi proposed that existing records could quantify downstream effects of febrile seizures on \nvaccine uptake, since diagnoses identify which children experienced a seizure and \nimmunization records show subsequent vaccinations. He cautioned that the lower observed risk after the second dose might reflect selection bias if children who reacted strongly to the first \ndose delayed or skipped the second dose. He also questioned the field’s limited mechanistic \nunderstanding, noting that a higher varicella antig en dose in MMRV may provoke a stronger \nimmune response in some children. He asked whether children who experience febrile seizures \nhave been evaluated for distinctive immune responses or biomarkers to clarify the underlying \nmechanisms, emphasizing that saf ety assessment should extend beyond symptoms to a \nbiological explanation.  \n \nDr. Pollak echoed concerns about limited mechanistic understanding and noted that very young \nchildren may have heightened IL -1–mediated fever responses. He asked whether cytokine \nlevels were measured in febrile children and whether cytokine gene polymorphi sms or other \ngenetic predispositions were assessed. He cautioned that second- dose findings may reflect \nselection bias if pediatricians avoid revaccinating children with a history of febrile seizures. He \nrecommended that guidance address how to manage vacci nation schedules for children who \nhave had prior febrile seizures.  \n Dr. Kulldorff agreed with the point that existing medical and immunization records could quantify \nwhether a febrile seizure affects subsequent vaccination for the child and younger siblings. He \nadded that he was not aware of any analysis that has examined this to date, though the data \nlikely exist to do so.  \n \nDr. Milhoan emphasized that febrile seizures are diagnosed retrospectively and that, for \nfamilies, a 15 -minute seizure feels incredibly long. He noted that in his practice, families who \nhave experienced a febrile seizure are often hesitant to proceed with the next vaccine, and he shares their caution. He asked whether fever from natural viral illness shares the exact \nmechanisms as vaccine- associated fever, highlighted that rising temperature lowers the seizure \nthreshold in all people, and questioned whether  the measles vaccine further lowers that \nthreshold. He observed increased vaccine hesitancy among families and emphasized the \n11 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  importance of clearly communicating the risks and benefits of vaccination. He also asked \nwhether there are long- term follow -up data on children who experienced a febrile seizure after \nthe first dose.  \n \nDr. Su stated that the request was to present data on the risk of febrile seizures and that he \nwould need to review data regarding longer -term outcomes.  \n \nDr. Stein asked how risks are communicated to parents and guardians in practice, noting that \nsome evidence predated the guidelines and additional data have been published since. She \nwondered how parental choice is incorporated into those discussions.  \n \nDr. Marin explained that one- pagers were developed to support risk communication: a provider \none-pager in table format outlining risks, benefits, and their implications, and a parent one- pager \nnoting the increased risk of febrile seizures with MMRV compared to MMR plus varicella. These \nmaterials were designed to help pediatricians discuss options in clear, understandable terms.  \n \nDr. Oliver added that usage data indicate about 85% of children receive separate MMR plus \nvaricella at the first visit, while roughly 15% receive MMRV. She noted this distribution likely \nreflects discussions between pediatricians and parents about risks and benefits.  \n Dr. Griffin inquired whether manufacturers or other groups are conducting studies on the \neducational performance of children following febrile seizures.  \n \nAn NCIRD SME shared that the group is not currently doing any long- term studies on the topic.  \n \nDr. Griffin noted that, since the product has been licensed since 2005, it would be helpful to \nreassure parents that studies on children’s educational outcomes after febrile seizures have \nbeen conducted. She also asked whether any studies were tested against a trustworthy saline \nplacebo.  \n \nDr. Su said a follow- up would be necessary to answer the question definitively. Most available \nstudies compare MMRV with MMR plus varicella.   \nDr. Griffin argued that comparing MMRV with separate MMR plus varicella introduces \nconfounding and makes risk interpretation difficult. She noted the usual rationale that vaccine \nversus saline placebo trials are considered unethical once a vaccine is deemed safe and \neffective. Still, she contended that, given current levels of parental non- vaccination by informed \nchoice, an actual placebo- controlled study could be ethical. She suggested inviting parents who \nhave already chosen not to vaccinate their childre n to participate, to enable a clearer \nassessment of the risks.  \n Dr. Marin explained that a placebo study would require a randomized controlled trial. Selecting \nonly parents who avoid vaccination would introduce confounding, as their children may differ \nsystematically (for example, prior adverse events). Participants cannot be chosen based on \nwillingness to forgo vaccination; they must consent to random assignment to either the vaccine \nor control group.  \n Dr. Oliver added that in a randomized controlled trial, participants must have an equal likelihood \nof receiving either a placebo or a vaccine, and families must consent to the randomization \nprocess. Given the currently elevated measles activity, asking par ents to accept a chance of a \n12 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  placebo, and therefore no protection against measles, mumps, rubella, or varicella, would be \nconcerning.  \n Dr. Griffin thanked Dr. Oliver for her response and shared that, in today’s environment, many \nparents are asking for more studies. She suggested that the public would welcome \nobservational studies comparing vaccinated and unvaccinated children.  \n \nDr. Kulldorff suggested that ethical randomized trials could be conducted by varying the timing \nof vaccination rather than withholding it, noting that countries recommend MMR at different \nages. For example, children could be randomized to receive MMR at 12  months versus 18 \nmonths, allowing randomized designs without denying vaccination.  \n \nDr. Blackburn asked why trials were designed with MMR and varicella given on the same day, \nnoting that simultaneous administration might produce adverse event rates similar to MMRV. \nShe suggested that separating MMR and varicella by at least 28 days could better distinguish \ndifferences in adverse reactions. She asked whether this approach had been considered, given \nthat typical pediatric visits occur at 12, 15, 18, and 24 months of age.  \n \nDr. Marin explained that trials were designed to compare MMRV with the same- day \nadministration of separate MMR plus varicella, because MMRV is intended to replace two injections with one. The primary question was whether a single injection would provide \ncomparable immunogenicity and an acceptable adverse event profile relative to administering \nboth vaccines at the same visit. While some studies included arms with MMR alone or varicella \nalone, most focused on the two practical options parents and providers f ace. Spacing MMR and \nvaricella across separate visits (for example, at 12 and 15 months) would not answer the \nsubstitution question because children would still receive two injections.  \n Dr. Pebsworth inquired whether the MMR/MMRV Vaccine Information Statement states that a \nprior febrile seizure or any post -vaccination seizure constitutes a contraindication, noting that \nthis relates to informed consent. She also referenced VSD findings that included both febrile \nand afebrile seizures and questioned whether the lack of statistical significance for second- dose \nevents at ages 4– 6 years might reflect selection bias. Additionally, she asked whether the \nassumption that febrile seizures are largel y benign is clinically justified and whether a history of \nfebrile seizures should be considered a contraindication to receiving the vaccine again.  \n \nDr. Oliver noted that the MMRV Vaccine Information Statement advises parents to consult their \nhealth care provider if the child has a history of seizures or if a parent or sibling has a seizure \nhistory. She added that the FDA sets contraindications.  \n \nDr. Marin added that the MMRV Vaccine Information Statement includes language under “Risks \nof a vaccine reaction”, noting that seizures, often associated with fever, can occur after MMRV. \nThe risk is higher with MMRV than with separate MMR and varicella when given as a first dose. \nThe VIS advises that a health care provider can recommend the appropriate vaccines.  \n \nDr. Meissner stated that febrile seizures occur in 3– 5% of children, are familiar to pediatricians, \nand have an excellent prognosis. He emphasized that while the episodes are frightening for \nfamilies, they are not associated with impaired neurocognitive development, school problems, or \nlong- term performance issues. He noted that the practical question is whether to use MMRV or \nseparate MMR plus varicella doses. Combination vaccines can improve completion rates by \nreducing the number of injections, whereas s eparating doses may reduce compliance. The \nargument against using MMRV at 12– 15 months is a slight increase in febrile seizure risk. He \n13 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  supported the current ACIP wording, which allows parents to choose based on their \npreferences: those concerned about febrile seizures may select separate MMR and varicella \nvaccines. In contrast, those prioritizing fewer injections may choose MMRV. He added  that \nabout 85% of children currently receive separate MMR and varicella at the first visit and \nconcluded that the existing guidance is appropriate.  \n \nDr. Levi expressed unease about assumptions underlying current interpretations. He cautioned \nthat febrile seizures after viral infection may differ biologically from those observed after \nvaccination and that measurement alone may obscure important mechanis tic differences. He \nurged agencies to investigate mechanisms, including biomarkers, and to follow children who experience seizures over the long term. He noted that higher antigen content may be \nassociated with more events and recommended that safety asses sments extend beyond 30– 40 \ndays.  \n \nDr. Meissner thanked Dr. Levi and responded that febrile seizures are well -defined: they occur \nin children, usually under 5 years (often under 4), are generalized rather than focal, last less \nthan 15 minutes (typically a few minutes), and do not recur within 24 hours. He noted that most \nfebrile seizures are not associated with vaccination and that the prognosis is excellent apart \nfrom the emotional impact on families. Given the limited resources and extensive pediatric \nexperience with these events, he quest ioned whether investing heavily in additional studies on \nvaccine -associated febrile seizures would be the most effective use of effort.  \n \nDr. Milhoan cautioned that heavy reliance on ICD codes can be problematic. As a practicing physician, he noted that selecting precise codes is often time -consuming and prohibitive, and \nretrospective analyses should account for this limitation. He emphasized the importance of \n“clean” data, suggesting a clear distinction between ICD -coded febrile seizures temporally \nrelated to vaccination and those not associated with vaccination. He urged researchers who use ICD-based datasets to acknowledge that these codes  are imperfect and may not fully capture \nclinical reality.  \n Dr. Pebsworth thanked Dr. Meissner for his comments and clinical perspective; however, she \nnoted a 2023 study on long- term neurodevelopmental outcomes of febrile seizures reporting \nclinical and animal evidence of potential adverse effects, including attention deficit hyperactivity \ndisorder, increased susceptibility to epilepsy, hippocampal sc lerosis, and cognitive decline in \nadulthood, while mechanisms remain unclear. She recommended adding this topic to a future agenda for safety review.  \n Rick Haupt, a Merck representative, noted that as a pediatrician, he witnessed fatal \npneumococcal, Hib, and varicella infections before they became vaccine- preventable and \nemphasized the importance of not returning to that era. He stated that ProQuad (MMRV ) has \nbeen rigorously evaluated in clinical trials and post -licensure studies, with findings shared with \nregulators, public health agencies, and medical societies, and published in journals. He \nreiterated that a slight increase in febrile seizures after the first dose was first reported in a 2009 \nobservational study with Kaiser and has informed current recommendations: MMRV is preferred \nfor the second dose, while separate MMR plus varicella is preferred for the first, with provider or \nfamily choice allowing  MMRV; about 15% choose MMRV at the first visit. He stressed evidence \nand consensus that combination vaccines improve series completion and on- time vaccination. \nHe cited recent CDC data showing kindergarten coverage below the 95% threshold needed for \nmeasl es herd immunity. He cautioned that policies that reduce clarity or consistency around \nMMRV could further erode public confidence. Addressing antigen content, he explained that \nonly the varicella antigen is higher in MMRV (the MMR antigens remain unchanged), which was \n14 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  necessary to demonstrate a non -inferior immune response compared with separate MMR plus \nvaricella, likely due to local antigen interference in the combination product.  \n \nDr. Kulldorff offered a correction, noting that the initial identification of an excess risk of febrile \nseizures with MMRV compared with MMR was made at CDC using the Vaccine Safety \nDatalink’s rapid cycle analysis. He said the signal was detected after approximately 25,000 doses and highlighted the strong work of the CDC and the VSD in monitoring vaccine safety.  \n \nDr. Hibbeln cautioned that the small risk of febrile seizures —likely without long -term \nconsequence— must be weighed against the danger of vaccination coverage falling below 90%, \nwhich could lead to devastating outcomes such as fetal loss, neonatal death, and congenital \nrubella syndrome. He stressed avoiding actions that might drive nonvaccinating through fear or \noversimplified “for or against” views of vaccines. He emphasized that any major change to long-\nstanding guidance should have a powerful, clearly art iculated rationale.  \n \nProposed recommendations and discussion  \nDr. Martin Kulldorff (ACIP Chair)  \n \nDr. Martin Kulldorff, Chair of the ACIP, presented the proposed recommendations from the \nMMRV Vaccine Work Group.  \n Proposed Recommendation:  \n \nThe pediatric vaccine schedule should be updated to reflect the following change:  \n-For measles, mumps, rubella and varicella vaccines given before age 4 years, the \ncombined MMRV vaccine is not recommended.  \n-Children in this age group should receive separate measles, mumps, and rubella \nvaccine and varicella vaccine (MMR+V).  \n \nDiscussion  \nDr. Stein asked how the proposed recommendation differs from current guidance, noting that \nthe 2009 recommendation appears to call for two separate shots for the first dose.  \nDr. Kulldorff outlined two differences. First, the proposal states that both options are acceptable, \nwith a preference for MMR plus varicella for doses administered between 12 and 47 months of \nage. Second, for children who receive a “second” dose before age 4 (for example, after an early \noutbreak dose at 7 months followed by a dose at 12– 15 months), that dose would be treated as \na pre -4-year dose so that the preference would be separate MMR plus varicella rather than \nMMRV.  \nDr. Levi stated that if adherence were guaranteed to be the same, separate MMR plus varicella \ndoses would be preferable, given the added adverse events with MMRV and the lower antigen \nexposure with separate vaccines. He questioned whether separating the fi rst-dose vaccines \nmeaningfully reduces adherence, suggesting that safer profiles likely increase trust and \nadherence. In the absence of strong evidence either way, he favored the option that appears \nsafer.  \nDr. Pebsworth sought confirmation that at the first visit (12– 15 months), approximately 85% of \nvaccinations are administered as separate MMR plus varicella and about 15% as MMRV.  \nDr. Kulldorff confirmed that at the first visit (12– 15 months), about 85% of vaccinations are \nadministered as separate MMR plus varicella, and roughly 15% as MMRV. He commended \n15 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  pediatricians and nurses for prioritizing the option associated with fewer febrile seizures and \nshared a brief personal example illustrating providers’ awareness of the rationale.  \nDr. Meissner shared two points. First, an MMR dose given before 12 months is intended for infants traveling to measles -endemic areas and does not count toward the routine two -dose \nseries; those children still need doses at 12– 15 months and 4– 6 years. He al so clarified that \nMMRV is licensed only for ages 12 months through 12 years. Second, he cautioned against \nremoving parental choice for the first dose, noting that while about 85% currently receive \nseparate MMR and varicella, some parents prefer a single vi sit with MMRV, and that option \nshould remain available.  \nDr. Goldman inquired whether a fully vetted Evidence to Recommendations (EtR) presentation \nwould be provided, addressing harms, benefits, acceptability, and feasibility, with input from \npracticing clinicians and liaisons. He argued the proposed recommendat ion could confuse the \npublic, does not reflect real -world clinician experience with vaccine hesitancy, and might enable \ninsurers and the Vaccines for Children program to decline coverage. He added that the change \nwould remove parental choice for informed decision -making with their physicians. He urged the \ncommittee not to change recommendations and, if proceeding, to use the established EtR process with transparent data to support debate and discussion.  \nDr. Hopkins agreed with Dr. Goldman.  \nDr. Middleman endorsed Dr. Goldman’s comments and emphasized the need to present all available evidence in a single, coherent, and scientifically vetted format, so that providers and \npatients can understand the full scope of information. She emphasized the  importance of \nfocusing on what the evidence reveals rather than beliefs unsupported by evidence.  \nDr. Kulldorff thanked Dr. Srinivasan and Dr. Su for their excellent and informative presentations.  \nDr. Levi requested clarification on what information had not been discussed or considered, \nnoting that prior comments had implied missing data. He asked whether anyone is disputing the \nevidence of increased febrile seizures after MMRV, and what additional data they believe \nshould be reviewed.  \nDr. Goldman argued that the discussion was not thoroughly vetted and relied too narrowly on \nselected data points without incorporating real -world clinical experience. He noted that liaison \nmembers have been removed from work groups, reducing subject matter  expertise and the \npatient voice. He emphasized that a complete assessment should address implementation, \nacceptability, feasibility, equity, and the balance of harms and benefits, and urged inclusion of \nphysicians’ practical experience with patients.  \nDr. Middleman echoed Dr. Goldman’s comments and requested that all available evidence be \npresented together, encompassing the full extent of scientific literature rather than only the few \nstudies discussed.  \nDr. Levi responded that he trusts the CDC staff to have presented all relevant data and noted that several colleagues are pediatricians with experience in patient care. He invited anyone who \nbelieves information is missing to specify it so the committee can consider it.  \nDr. Hopkins appreciated the CDC data, describing it as thorough and informative, but noted that equity considerations and the practical implications for patients and practicing physicians had \nnot been adequately addressed. He stated that without a full Evi dence to Recommendations \n(EtR) review of these elements, the committee lacks a complete basis for decision- making.  \nDr. Goldman agreed with Dr. Hopkins.  \n16 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  Dr. Jshlay emphasized practical considerations at the 12- month visit, noting that children may \nreceive multiple vaccines and some parents prefer fewer injections. She estimated that up to 7 \nvaccines can be given at a single visit and underscored the need f or informed consent and \nalignment with parental preferences when scheduling and selecting vaccines.  \nDr. Stein noted that the Vaccine Information Statement indicates an increased risk of fever and \nseizures after the combined MMRV shot compared with separate MMR and varicella shots. She asked how this risk is communicated to parents in practice and whether  clinic time pressures, \nsuch as busy patient flow, ever limit the ability to provide clear informed consent. She invited \ninput from medical professionals on how these discussions are handled.  \nDr. Milhoan suggested asking parents directly about the adequacy of risk and benefit \ndiscussions rather than relying solely on clinicians’ perspectives. He noted that in busy \npractices, informed consent is often incomplete across various medicines and vacc ines, with \nrare but serious risks not always being thoroughly reviewed. He said that many parents felt they were given little information and concluded that current practices may not fully meet the \nstandard for informed consent.  \nVFC Resolution Update: MMRV Vaccine  \nJeanne Santoli (CDC/NCIRD)  \n \nJeanne Santoli (CDC/NCIRD) presented the VFC resolution update with all revisions from the \npreviously approved resolution shown in red. The purpose of the update is to provide revised \nguidance on the use of the combined measles, mumps, rubella, and varicel la (MMRV) vaccine. \nThe resolution includes three components: MMR, varicella, and the combined MMRV. No changes were made to the MMR or varicella components; eligibility, recommended schedules, \ndosage intervals, contraindications, and precautions remain the same. The changes apply only \nto the combined MMRV component and clarify eligible groups, recommended schedule, \ndosage, and contraindications to align with the proposed recommendations under discussion \ntoday by the ACIP.  \n \nDiscussion  \nDr. Kulldorff noted that, as is standard procedure, two votes will be conducted. The first will address the recommendation, followed by a separate vote on the VFC resolution. He added that \nthis approach is consistent with the process used during the June m eeting.  \nDr. Griffin echoed comments from Dr. Milhoan, noting from her personal experience as a mother \nthat vaccine information statements were not always consistently explained when her children \nreceived immunizations, with the expectation that parents would read the handout \nindependently. She added that many of her patients and non- physician acquaintances had \nreported similar experiences, although she acknowledged that this was anecdotal. Dr. Griffin \nemphasized the value of having additional data for committee rev iew and clarified her earlier \ncomments regarding randomized controlled trials, acknowledging the ethical limitations of such \nstudies. She concluded by stressing the importance of considering a broader range of studies \nand raw data, as well as individual ex periences that collectively inform the balance of vaccine \nbenefits and risks.  \nDr. Jshlay shared that at the Public Health Institute of Denver Health, her large- scale \nimmunization program provides the VFC and VIS forms before vaccination and reviews them \nwith patients to ensure informed decision- making. She emphasized that providing the VIS \nbefore vaccination is a requirement and noted that local public health agencies across the \ncountry follow this same practice. She added that, although she could not comment on \nanecdotal reports, her clinic strives to uphold this standard.  \n17 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  Dr. Middleman emphasized the importance of grounding public health recommendations in a \ncomprehensive body of data rather than anecdotal evidence. She noted that while physicians \nfocus on individual patients, public health decisions must consider the healt h of the entire \npopulation. She highlighted the breadth of studies that inform the evidence -to-recommendation \nprocess and stressed the need to evaluate all elements of public health, including disease \nimpact, risks and benefits, feasibility, acceptability,  cost-benefit ratio, and equity. Dr. Middleman \nquestioned the urgency of deciding at this meeting and urged the committee to follow a \nmethodical evidence -to-recommendation process to ensure scientific rigor and maintain public \nconfidence.  \nDr. Kulldorff apologized for sharing an anecdote about his twins’ vaccinations but noted that the \ncommittee had engaged in a strong, science -based discussion. He commended the CDC \ncolleagues for their presentations and highlighted the quality of the debate  on various aspects of \nthe vaccines.  \nDr. Pebsworth acknowledged that at the 12– 14-month visit, many vaccines are administered \nand noted that approximately 85% of pediatricians and parents currently choose MMR plus \nvaricella separately. She then raised a technical question regarding the language of the posted \nvote, which states “recommends.” She sought clarification on whether this language would \nprohibit the use of the FDA -licensed MMRV vaccine for certain patients, emphasizing the \nimportance of preserving provider discretion to administer lic ensed products.  \nDr. Kulldorff clarified that the committee’s role is to make recommendations, while the FDA determines which vaccines can or cannot be used. He noted that committee votes may have \nconsequences for insurance coverage, including through CMS, but emphasized t hat the \nauthority to approve vaccine use rests with the FDA.  \nDr. Srinivasan suggested that it would be helpful for a VFC representative to comment on how \nACIP recommendations affect the Vaccines for Children program, given that the program funds \nmany pediatric vaccines.  \n Dr. Santoli explained that if a vaccine is designated as “not recommended,” it will not be \ncovered under the VFC program for children. She noted that while there are ways to address \nindividual -based decisions that allow for coverage, the current resolution under consideration \nwould mean that VFC would not cover the vaccine even if a parent and physician chose it.  \n \nDr. Johnson added that a “not recommended” designation could also affect coverage under \nMedicaid and the Children’s Health Insurance Program, as well as individual and group \ninsurance markets. She noted that this could impact overall coverage and potential ly result in \nout-of-pocket costs, such as co -pays.  \n \nDr. Kulldorff clarified that the coverage discussion pertains specifically to the MMRV vaccine. He \nemphasized that coverage for the MMR and varicella vaccines will remain unchanged, with both \ncontinuing to be fully covered.  \n \nDr. Johnson confirmed.  \n Dr. Hibbeln requested clarification that under the proposed change, administration of the MMRV \nvaccine before four years of age would be considered “not recommended,” and therefore would \nnot be covered for payment.  \n Dr. Santoli clarified that, under the Vaccines for Children program, the MMRV vaccine would not \nbe covered for children under the age of four.  \n18 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.   \nDr. Hibbeln expressed concern that under the proposed change, parents would lose the option \nto choose the MMRV vaccine for their child unless they were willing to pay out of pocket. He \nnoted that if parents preferred a single vaccination rather than multiple shots, this option would \neffectively be taken away despite their understanding of the risks and benefits.  \n \nDr. Santoli confirmed that VFC would not cover the vaccine for those children.  \n \nVote: MMRV Vaccines Vote \nDr. Martin Kulldorff (ACIP Chair)  read the following proposed ACIP voting language for \nMMRV vaccines into the record:  \nThe pediatric vaccine schedule should be updated to reflect the following change:  \n-For measles, mumps, rubella and varicella vaccines given before age 4 years, the \ncombined MMRV vaccine is not recommended.  \n-Children in this age group should receive separate measles, mumps, and rubella \nvaccine and varicella vaccine (MMR+V).  \n \n \nMotion/Vote: MMRV Vaccines   \n \nDr. Levi motioned to approve the recommended voting language, stating,  \n“The pediatric vaccine schedule should be updated to reflect the following change:  \n-For measles, mumps, rubella and varicella vaccines given before age 4 years, the combined \nMMRV vaccine is not recommended.  \n-Children in this age group should receive separate measles, mumps, and rubella vaccine and \nvaricella vaccine (MMR+V).”  \nDr. Pagano seconded the motion. No COIs were declared. The motion carried with 8 votes in \nfavor, 3 votes opposed, and 1 abstention. The disposition of the vote was as follows:  \n \n    8 Favored:  Pagano, Milhoan, Stein, Griffin, Pollak, Pebsworth, Levi, Kulldorff  \n    3 Opposed:   Blackburn, Hibbeln, Meissner  \n    1 Abstained:  Malone  \n Discussion  \n Dr. Santoli requested clarification on the wording used during the vote discussion, noting that \nshe had heard the term “compensate” and wanted to ensure it was understood correctly. She \nexplained that a yes vote would align the VFC resolution with the recommendation vote that had \nalready passed, meaning the combination vaccine would not be covered in VFC for children \nunder four years of age. A 'no' vote would maintain the current VFC coverage as it stands today, \nwhich includes the combination vaccine for children aged 12 months through 12 years. She \nacknowledged that timing issues had prevented the full written materials from being available \nbefore the meeting, as the resolution had to be made late the previous evening to align with the \ncommittee’s proposed language.  \n \nA CMS representative confirmed that the same coverage decision would apply to Medicaid, \nCHIP, and the individual and small group markets, clarifying that the combined vaccine for \nchildren under four years would not be covered if the resolution were to pass . \n \n19 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  Dr. Meissner expressed confusion, asking what would happen if the committee voted no, and \nemphasized the need for clarity.  \n Dr. Santoli reiterated that a no vote would maintain VFC coverage unchanged, meaning the \ncombination vaccine would remain covered; however, CMS and VFC could ultimately have \ndifferent coverage policies, potentially creating confusion.  \n \nDr. Malone commented that it was difficult for the committee to vote without a written text of the \nresolution, even though the presentation was clear, and suggested that complete written \ninformation be provided in the future.  \n \nDr. Pagano sought clarification on whether a recommendation automatically leads to \nreimbursement.  \n \nDr. Levi stated that his understanding was that there are two parallel decisions: the \nrecommendation and the resolution. If no new approval is granted, the previous decision \nremains in effect.  \n \nDr. Pagano noted that this process seemed convoluted, as the committee was being asked to \nvote no to maintain coverage.  \n Dr. Milhoan requested clarification on the relationship between the VFC and CMS programs. Dr. \nSantoli explained that VFC covers Medicaid, uninsured children, American Indian and Alaska Native children, and underinsured children served in federally qualified health centers, while \nCHIP is administered separately under CMS.  \n A CMS representative confirmed that CHIP and the individual markets are not directly affected \nby this vote but rather by the broader ACIP recommendation.  \n \nWhile there was a VFC vote on the initial day of the meeting, with the results of 1 in favor, 8 \nopposed, and 3 abstained, the committee decided to reconsider the vote due to not fully \nunderstanding the implications. Dialogue to follow:  \n \nDr. Kulldorff noted that most members were still new to ACIP and might not yet grasp specific \ntechnical issues. He explained that after the meeting, a member had raised concerns about the \nsecond vote taken on the VFC resolution regarding the MMRV vaccine a nd whether the \ncommittee had fully understood the implications. He stated that VFC votes are typically aligned to ensure equal coverage and access for all children, and that some consideration had been \ngiven to resolving the conflicting votes.  \n \nDr. Pebsworth moved to reconsider the VFC resolution on MMRV that had been voted on the \nprevious day.  \n Dr. Griffin seconded the motion.  \n \nDr. Kulldorff explained that the committee would first vote on whether to reconsider the matter. If \nthat vote passed, the resolution itself would then be voted on a second time. He asked \nmembers to state their names, declare any conflicts of interest, and indicate their votes. Results \nto follow:  \n \n20 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  Vote: To Reconsider the original MMRV Vaccines-  VFC Vote  \n \nMotion/Vote: MMRV Vaccines   \n \nDr. Pebsworth motioned to reconsider the VFC resolution vote voted on September 18, 2025. \nDr. Griffin seconded the motion. No COIs were declared. The motion carried with 10 votes in \nfavor, 0 votes opposed, and 2 abstentions. The disposition of the vote was  as follows:  \n \n    10 Favored:      Levi, Pebsworth, Hibbeln, Pollak, Griffin, Stein, Blackburn, Milhoan, Pagano, \nKulldorff  \n    0 Opposed:    \n    2 Abstained:  Malone, Meissner  \n \nDiscussion  \nDr. Goldman, representing the American College of Physicians, expressed concern about the \nvote taken the previous day because the committee had two conflicting votes on the same \nresolution, with the second primarily affecting children from lower socioeconomic backgrounds. \nHe questioned whether the outcome of the first vote implied that children from lower \nsocioeconomic groups should only receive what the committee had described as a harmful \nvaccine, or whether the second vote revealed that there was no evidence of harm from MMRV \nand that the risk was not a concern. He argued that the second vote should be considered valid \nfor the entire population, as it indicated that there was insufficient data to support claims of \nharm.  \n \nDr. Levi stated that the chair had already explained there was an error in the interpretation of \nthe votes and suggested that the committee focus its time on scientific debate rather than \npursuing discussion without merit.  \n Dr. Hibbeln stated that the committee had acknowledged the wording of the second vote was confusing and imprecise. He remarked that, considering the extensive work by CDC and the \ncommittee, the confusion was mainly due to wording and expressed appreciation for the more \nprecise phrasing now provided.  \n \nDr. Kulldorff emphasized that the vote’s outcome ensures every child, including those in the \nVaccines for Children program, will have access to vaccination against measles, mumps, \nrubella (also known as German measles), and varicella (chickenpox). He stated that this guarantees all children will be able to receive protection against these four critical diseases.  \n Vote: MMRV Vaccines - VFC Vote  \nDr. Martin Kulldorff (ACIP Chair)  read the following proposed ACIP voting language for \nMMRV vaccines into the record:  \nApprove the updated Vaccines for Children (VFC) resolution for prevention of measles, \nmumps, rubella and varicella.  \n \n \nMotion/Vote: MMRV Vaccines   \n \n\n21 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  Dr. Levi motioned to approve the recommended voting language to approve the updated \nVaccines for Children (VFC) resolution for prevention of measles, mumps, rubella and \nvaricella. Dr. Pebsworth seconded the motion. No COIs were declared. The motion carried \nwith 9 votes in favor, 0 votes opposed, and 3 abstentions. The disposition of the vote was as \nfollows:  \n \n   9 Favored:  Levi, Pebsworth, Hibbeln, Pollak, Griffin, Stein, Milhoan, Pagano, Kulldorff  \n   0 Opposed:    \n   3 Abstained:  Blackburn, Malone, Meissner  \n \n \nHEPATITIS B VACCINE S \n Introduction  \nDr. Martin Kulldorff (ACIP Chair) \nACIP Chair Dr. Martin Kulldorff  opened the session by introducing the Hepatitis B Vaccine. He \nexplained that the focus of the discussion today  was very specific: to evaluate only the birth \ndose of the hepatitis B vaccine given within 24 hours of birth, and only for infants whose \nmothers have tested negative for hepatitis B. He clarified that no changes are being considered \nfor infants born to mothers who test positive or whose status is unknown.  \nHepatitis B Birth Dose Vaccination  \nDr. Adam Langer (CDC/NCHHSTP)  \n \nDr. Adam Langer (CDC/NCHHSTP) presented on Hepatitis B birth dose vaccination. Hepatitis B \nvirus (HBV) infection causes hepatitis B, which affected an estimated 254 million people \nworldwide in 2022. While some infections clear naturally, many progress to chronic hepatitis B, \nan incurable condition that can lead to severe liver disease, liver cancer, and death.  \n HBV can be transmitted from mother to child (perinatal transmission) as well as through household or community exposure. [hepatitis B is easily transmitted through relatively casual \ncontact; sexual contact or sharing of needles is not required to transmit the virus to others.] \nWithout intervention, up to 85% of infants born to HBV -infected mothers will become infected. \nRisk of developing chronic infection is highest in children: about 90% of infants perinatally \ninfected develop chronic hepatitis B, and roughly 25% infected in childhood die prematurely from related complications.  [Likelihood of chronic infection increases inversely with age, so the \nyoungest children (i.e., newborns and infants) are at greatest risk.]  \n \nIn the U.S., an estimated 2.4 million people are living with hepatitis B, about half unaware of \ntheir infection. Roughly 70% of those with chronic hepatitis B were born in countries with intermediate to high prevalence, often infected at birth or early chi ldhood.  [Chronic hepatitis B is \nincurable and can ultimately be fatal, so immunization against hepatitis B is lifesaving, and the earlier in life the vaccination series is started, the more lives that will be saved and severe \nchronic illness that will be p revented.]  \n \n22 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  Vaccination programs have reduced hepatitis B among U.S. children, but most reported cases \nnow occur among unvaccinated adults. In 2023, about 14,400 acute cases were estimated, with \nthe highest rates in adults aged 40– 59 years.  \n \nChronic hepatitis B carries significant healthcare costs. Analysis of claims data from 2004 to \n2015 showed annual per -patient costs (adjusted to 2015 dollars) ranging from approximately \n$94,000 for less severe disease to roughly $325,000 for those requiring a liver transplant. \nOverall, more than $1 billion is spent annually on hepatitis B -related hospitalizations in the U.S.  \n \nTwo products prevent perinatal hepatitis B virus (HBV) infection: the hepatitis B vaccine, which \nprovides long- term protection and is used for both pre - and post -exposure prophylaxis, and \nhepatitis B immune globulin (HBIG), which offers temporary protection in specific post -exposure \nsettings.  \n \nWhen used together, vaccination and HBIG prevent about 94% of mother -to-child \ntransmissions. The hepatitis B vaccine is the cornerstone of prevention, with effectiveness \nincreasing the sooner the birth dose is given after delivery.  \n \nThe hepatitis B vaccine, available in the U.S. for more than 40 years, was the first vaccine to \nprevent infection with a cancer -causing virus. Two single- antigen recombinant vaccines are \nFDA-approved for use from birth: Recombivax HB (1986) and Engerix -B (1989). [These \nvaccines were tested using placebo- controlled randomized trials prior to licensure in the United \nStates, so there is no need to do additional placebo- controlled studies now.] Extensive research \nand reviews by the Institute of Medicine and WHO  confirm the vaccine’s safety and \neffectiveness.  [The vaccine has been routinely given to all newborns in the United States since \n1991, and very few serious adverse effects of the vaccine have been identified over the 34 years that this vaccine has been in routine use. The worst reported adverse effect,  anaphylaxis, \nis literally a one in a million occurrence, and this extremely rare reaction can be addressed with \nimmediate treatment and causes no long- term injury to the vaccinated person.]  \n \nFull hepatitis B protection requires a multi -dose series, typically three doses. Protective antibody \nresponses are seen in 25% of infants after the first dose, 63% after the second dose, and 98% after the full three- dose series. Immunity can last for decades; one Alaska- based study showed \nthat more than 90% of individuals retained protection over 30 years after vaccination.  [The \nsooner the vaccination series is started, the sooner that the child is protected.]  \n \nSince 1988, universal screening for hepatitis B surface antigen (HBsAg) has been \nrecommended for pregnant women, with additional testing for at -risk women later in pregnancy \nor at delivery. Vaccination at birth has been recommended since 1984 for infants o f women \ntesting positive, with the timing specified as within 12 hours of birth starting in 1988. HBIG administration has also been recommended within 12 hours for infants of HBsAg- positive \nwomen since 1984, and since 2018 for infants under 2,000 grams bor n to women with unknown \nresults.  \n \nIn 1991, the U.S. adopted universal infant hepatitis B vaccination. Guidance on the timing of the \nbirth dose has evolved from “before hospital discharge but no later than 2 months” (1991), to \n“administered in the birth hospital” (2005), to “within 24 hours  of birth” (2018).  \n The universal hepatitis B birth dose provides a critical safety net for infants who may have \nunrecognized HBV exposure during pregnancy or early childhood, which can lead to severe \noutcomes. Gaps in post -exposure prophylaxis occur due to lack of prenatal c are, missed \n23 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  screening, or administrative errors. One reported case involved a mother with a positive test \nresult that was miscommunicated, resulting in her infant not receiving prophylaxis and later \ndying from fulminant hepatitis. Between 1999 and 2002, more than 500 similar transmission \nevents were documented when prophylaxis was not administered.  \n \nIn the U.S., 12– 16% of pregnant women receive inadequate or no prenatal care, and a similar \npercentage are never tested for hepatitis B. The national perinatal hepatitis B prevention \nprogram identifies less than half of infants born to HB sAg-positive mothers annually, \nunderscoring the importance of universal birth dose vaccination.  \n \nThe birth dose also protects against household or community transmission. HBV can survive for \nover seven days on surfaces, and even microscopic amounts of blood or body fluid are \nsufficient to transmit the infection. Unvaccinated infants are at risk if they live with or are cared \nfor by individuals with chronic HBV, many of whom are unaware of their infection. Studies \nbefore widespread use of the birth dose showed 7– 11% of U.S. -born children of immigrant \nmothers with no HBV evidence tested positive, pointing to community exposure.  [Even for \ninfants born to mothers known to be HBsAg- negative, the birth dose and subsequent doses \nprovide crucial protection against household and community (e.g., daycare) exposures that \ncould occur as soon as the infant leaves the hospital.]  \n Initiating the hepatitis B series on the first day of life offers early protection and benefits infants \nof both positive and negative mothers. It poses no increased risk of adverse events compared to \nlater vaccination.  \n \nOver t hree decades of data- driven, evidence- based hepatitis B vaccination recommendations \nfor newborns and infants have led to significant reductions in U.S. acute hepatitis B cases. Following the 1991 recommendation for universal infant vaccination (within 12 hours for infants \nof mothers with unknown status), the number of reported acute cases fell by 69%, from 18,003 \nin 1991 to 5,494 in 2005. Following the 2005 guidance to administer the first dose before \nhospital discharge, later updated in 2018 to withi n 24 hours of life, cases dropped an additional \n60% to 2,214 in 2023. However, after adjusting for underreporting, the estimated actual number \nof 2023 cases was 14,400.  \n \nRescinding the universal birth dose recommendation poses risks, including more perinatal HBV \ntransmission, increased lifetime risk of severe liver disease, added administrative complexity, \ngaps in care, reduced vaccine series completion, and higher lifetim e healthcare costs. Harms \nwould fall disproportionately on uninsured or low -engagement patients. The only potential \nbenefit is a reduction in already rare adverse events; serious events, such as anaphylaxis, occur \nat a rate of 1.1 per 1 million doses.  \n \nCDC was asked to address four specific questions related to the hepatitis B birth dose. The first \ntwo questions, reviewed in this session, concern hepatitis B vaccination recommendations in \ndeveloped countries: specifically, the recommended age of the firs t dose for infants born to test -\npositive mothers and for all other infants, and the prevalence of hepatitis B infection among \npregnant women. The remaining two questions will be addressed later by colleagues from the \nImmunization Safety Office.  \n Countries differ in their approaches to the birth dose. Some recommend a universal birth dose \nfor all infants regardless of maternal status, others recommend it only for infants of HBV -positive \nmothers, some provide a universal birth dose in limited regions, and some have no \nrecommendation at all. Currently, 43 countries do not have a birth dose policy; however, with \n24 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  Gavi support beginning in 2024, many of these countries are either introducing the birth dose or \nhave expressed plans to do so within the next three to five years.  \n Among the 38 countries reviewed by ACIP, 36, including the U.S., recommend a birth dose \nwithin 24 hours along with HBIG for infants born to HBV -positive mothers. The only exceptions \nare Ireland and Denmark, though both generally provide the vaccine within 24 hours. For infants \nborn to test -negative mothers, eight countries provide a universal birth dose within 24 hours. Of \nthe 38 countries, 26% limit the birth dose to infants of HBV -positive mothers but still recommend \nroutine infant vaccination later. Canada’s policies differ by province. Only four countries, \nDenmark, Finland, Iceland, and New Zealand, limit the birth dose to infants of HBV -positive \nmothers and do not offer universal infant vaccination.  \n \nThe most recent prevalence data from 2023 or the past 10 years for hepatitis B among pregnant \nwomen were available in 20 of the 38 countries. Nine reported prevalence below 0.5% and all \nused selective birth dose policies. Eight countries reported prevalenc e between 0.5% and 0.9%, \nwhile three reported prevalence greater than 2%. No U.S. prevalence data have been available \nin the past 10 years. Only six of the 38 countries maintain national registries to track HBV \nprevalence in pregnant women, while the other  32, including the U.S., do not collect this data \nregularly.  \n \nScreening data were available in 19 of the 37 comparator countries. Several countries met the \n2030 global target of screening 90% or more of pregnant women. In the U.S., an estimated 14% \nof pregnant women are not screened, placing the U.S. below the target . The U.S. is one of five \ncountries not meeting the goal and one of only three without universal healthcare coverage. \nUnlike the U.S., most countries provide universal health coverage, ensuring access to prenatal \ncare and vaccination, which supports higher  screening rates and timely prophylaxis. This \ndifference highlights the importance of the universal birth dose in the U.S. as a safety net for \ninfants born to mothers with unknown HBV status. Notably, no country has reverted from \nuniversal to selective bir th dose, and several are moving toward universal adoption.  \nThe second question requested a systematic review of randomized trials on administering the \nhepatitis B vaccine within 24 hours of birth. The updated review screened 1,390 studies in \naddition to 833 from the existing review. Seventeen studies met the inclusion criteria, including \nseven from the earlier review and 10 from the update.  \n \nThe risk of bias assessment revealed a high overall risk, primarily due to unclear methods of \nrandomization and limited reporting on whether investigators were blinded to the outcomes, \nwhich could impact the results. The 17 studies were grouped by intervention type, including \nefficacy, timing of vaccination, product or formulation differences, dose and schedule, and HBIG \nco-intervention. Outcomes of interest included protection, efficacy, and safety.  \n \nEfficacy trials demonstrated high levels of protection among infants born to HBV -positive \nmothers. Birth dose vaccination alone reduced transmission by up to 94% and combining the vaccine with HBIG reduced transmission by up to 99%. Adverse events were few  and generally \nmild, such as low -grade fever.  \n A timing study among infants of HBV -negative mothers compared vaccination at birth, 2 \nmonths, or 6 months, with a control group starting at 18 months. All timing groups showed high levels of protection (91%) with no significant safety differences.  \n \n25 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  Several product and formulation trials comparing different hepatitis B vaccines found them to be \nnon-inferior. Across studies, high levels of seroprotection and equivalent efficacy in preventing \nperinatal transmission were observed, with few reported adver se events.  \n \nDose and schedule trials showed strong seroprotection in both HBV -positive and HBV -negative \ninfants. One study reported 96% seroprotection in the intervention arm compared to 0% \nseroprotection in the comparator arm with no birth dose. Efficacy was consistently high across \ngroups, and safety profiles were similar, with very few local or systemic adverse events.  \n \nThe updated systematic review did not identify any new placebo- controlled trials assessing \nefficacy, which is unsurprising since the vaccine’s efficacy was established in the 1980s, and \nwithholding it would be considered unethical. There was limited report ing for pre- term, low \nbirthweight, and extremely low birthweight infants, and no morbidity or mortality outcomes were \nreported. The studies were heterogeneous, and many were conducted before the CONSORT \nstatement was widely adopted, resulting in weaker reporting standards. The risk of bias was \nprimarily associated with randomization and outcome measurement; however, even studies with \na high risk of bias can provide helpful information if the findings are consistent and the effects \nare significant.  \n \nDr. Langer concluded that the body of evidence from both the existing and updated systematic \nreviews supports the birth dose as safe, effective, and capable of inducing strong seroprotection \nin infants born to mothers who are both test -positive and test -negative. CDC interprets these \nfindings as continued support for the ACIP’s universal birth dose recommendation, first made in \n1991 and later strengthened in 2005 and 2018 as part of the national strategy for hepatitis B \nelimination.  \n Discussion  \n \nDr. Griffin asked how many of the 17 studies included in the review had declared a conflict of \ninterest.  \n Dr. Nyendak , an SME who oversaw  the rapid systematic review, stated that, to her knowledge, \nthere were no reported conflicts of interest but noted they would confirm and provide that \ninformation later.  \n \nDr. Griffin noted that the ACIP group does not have open access to journals, and purchasing \nindividual studies can cost $45 to $60 each, which becomes a significant barrier when reviewing \nhundreds of studies. In reviewing the 17 studies included in the systematic review, she found \nthat eight declared conflicts of interest. Among the studies focused on adverse events, five of \nthe eight had declared conflicts, while three others had unclear declarations. Several involved \npharmaceutical funding, where companies both funded the study and provided the vaccine. She \nexpressed concern about this issue and then referenced CDC data, stating that there were 912 \nhepatitis B -related deaths in 1991, the year the vaccine was approved, compared to 1,740 \ndeaths in 2021. She asserted  that percentage rates indicate an increasing death rate despite \nthe adoption of the vaccine and asked what accounts for this change.  \n \nDr. Nyendak  clarified that  after conferring with the systematic review team in real time,  the team \nwas aware of three studies that reported conflicts of interest and provided this as a correction to \nthe record.  \n \n26 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  Dr. Wester from the Division of Viral Hepatitis stated that the team would investigate the \nquestion further regarding hepatitis B death rates. She noted that, for surveillance purposes, \nreportable death rates come through the National Vital Statistics Syst em and that reporting \npractices have evolved significantly over the decades referenced.  \n \nDr. Levi reviewed the data by age group and noted that vaccination of infants born to HBV -\npositive mothers clearly reduced cases in children aged 0– 19. However, he observed that after \nthe 2005 recommendation for universal birth dose, further reductions mai nly appeared in older \nage groups rather than in young children. He questioned whether the data demonstrate an \nadded benefit of universal vaccination at birth for infants of test -negative mothers living in typical \nenvironments. Dr. Levi emphasized that the vaccine is critical for infants born to HBV -positive \nmothers and other high- risk populations but expressed uncertainty about the evidence \nsupporting universal administration to all newborns.  \n Dr. Langer responded to Dr. Levi, identifying two questions: why declines are more visible in \nolder age groups than in younger ones, and whether there are data on community and \nhousehold exposures. He explained that the observed declines in older groups reflect a birth \ncohort effect, where individuals vaccinated as infants in the early 1990s have since aged into \nolder cohorts. As time passes, those who benefited from early vaccination policies move into \nolder  age categories, which explains the shifts seen i n the data.  \n Dr. Levi observed that since universal birth dose vaccination began prior to hospital discharge in \n2005, infants born after that year would not yet have aged into the older cohorts where declines \nare being measured. He suggested that any measurable impact of the universal policy may not \nbe evident until these cohorts are older. He noted that current data may not yet show a \nmeaningful effect.  \nC \nDr. Stein asked about the incidence of hepatitis B in children born to mothers confirmed as \nhepatitis B negative, noting this would help understand the risk. She also pointed out that only \ntwo of the reviewed clinical trials specifically stratified childre n born to negative mothers, and \nboth were rated as high risk of bias. She asked how reliable the data are on hepatitis B \nincidence in this group.  \n \nAn SME referred to slide 30, noting that in dose and schedule trials involving infants of hepatitis \nB surface antigen– negative mothers, efficacy was equivalent between intervention and \ncomparator groups. The randomized efficacy literature has focused more on infants of surface \nantigen– positive mothers, where outcomes such as seroprotection, efficacy, and safety are \nmore measurable and show larger effect sizes. Infections among infants of negative mothers \ntypically result from missed or late maternal infecti on or early horizontal exposure from a \nhousehold member or caregiver. This underscores the rationale for a universal birth dose as a \nsafety net. Data have shown a 7– 11% prevalence of infection among U.S. -born children of \nimmigrant mothers with no evidence of maternal infection, reflecting community or household \ntransmission as the only plausible explanation. The universal birth dose policy was adopted \nafter risk -based strategies failed to prevent perinatal and early childhood transmission, with only \n26% of acute hepatitis B cases linked to a reported risk factor , [and the universal birth dose \npolicy has been demonstrated to be highly successful in reducing incidence of new hepatitis B \ninfections in the United States.]  \n Dr. Kulldorff commented that although U.S. data on hepatitis B prevalence among pregnant \nwomen were not available, estimates based on women aged 20– 40 suggest a prevalence of \nabout 4– 5% overall, with less than 0.1% among U.S. -born women. He noted that roughly 80% \n27 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  of infections are among immigrants and 20% among U.S. -born women, emphasizing that U.S. \nrates are very low compared to Western European countries, where only Portugal has a \nuniversal birth dose policy. He also reviewed adverse event data, noting five local ized and ten \nsystemic events among 178 vaccinated infants compared to three localized and four systemic \nevents among unvaccinated infants. Although overlap between localized and systemic events \nwas unclear, combining them produced a borderline statisticall y significant result (p = 0.054) \nwith a relative risk slightly above two. Although the sample size was small, the data suggest \nsomewhat higher adverse events for infants vaccinated at birth, which should be considered in \ndeliberations.  \n Dr. Levi inquired about the duration of the clinical trials for safety monitoring and the \nsurveillance time window for these results.  \n \nDr. Kulldorff responded that he believed it was short -term.  \n \nDr. Levi then asked whether the short -term safety monitoring period in the trials was only a few \ndays, such as up to five, and clarified that if so, the data may suggest higher adverse events in the first days after vaccination but provide no information beyond that period.  \n \nAn SME directed participants to slides 44 and 45, which show sample sizes and follow -up \nperiods in months. Most safety data were collected after the first dose, with monitoring beginning at 24 hours. The follow -up periods were  shown for study  and ranged from five to 24 \nmonths.  \n Dr. Levi asked whether data from the longer follow -up periods could be used to compare \nadverse events overall.  \n \nSME responded that the studies reported safety outcomes for as long as each study continued.  \n \nDr. Milhoan asked what specific signals were being tracked during follow -up, noting that if the \nperiod extended to 24 months, it would be important to know whether the criteria included \nhospitalizations, fevers, hepatitis, or other potential adverse reacti ons, especially since children \nwould have received additional vaccines during that time.  \n \nSME explained that slide 41 of the extra slides shows the time points used in the studies. \nSeroprotection was reported at the first time point after the last dose in the series. Efficacy was \nmeasured at the latest available time point with the ongoing intervention, and safety was assessed at birth at the closest time point immediately after the birth dose, as  requested.  \n \nDr. Milhoan asked if it was for seroprotection rather than side effects.  \n SME clarified that it referred to the follow -up period.  \n Dr. Levi requested clarification on whether there were any follow -up reports of side effects \nbeyond the first few days after birth.  \n SME responded that follow -up varied across studies and said they would provide clarification \nlater.  \n \nDr. Wester responded to questions about the prevalence of hepatitis B infection in the U.S. She \nexplained that there is no disease surveillance registry to answer this directly, but NHANES data \n28 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  from 2013– 2018 estimated national prevalence at 0.3%. She noted this may underrepresent \npopulations with the highest burden. Stratification revealed a similar prevalence among males \nand females, as well as among reproductive- age adults (25– 49 years). By co untry of birth, \nprevalence was 0.1% for U.S. -born individuals and 1.2% for non- U.S.-born individuals. A \nmodeling study estimated that in 2015, approximately 0.5% of U.S. births were to women who \nwere HBsAg -positive, with 40% of these women being U.S. -born and 60% non- U.S.-born. She \nalso noted that evolving recommendations over the past three decades have had a generational \nimpact. Finally, she clarified that the 1991 infant vaccination recommendation was intended for \nadministration before hospital discharge . However, it allowed vaccination up to two months of \nage, with a preference for vaccination before discharge.  \n \nDr. Malone asked if there were data on the number needed to treat to prevent a case of \nhepatitis B in a child born to an HBsAg- negative mother in the U.S. population.  \n \nDr. Wester replied that such data are  not available. She noted, however, that if delaying the first \ndose for infants of test -negative mothers were considered, it would be important to have \nmodeling data to estimate potential harms from unrecognized exposures during pregnancy or \nearly childhood.  \n \nDr. Malone added that to assess the risk -benefit reasonably, more granular data on the number \nneeded to treat for infants of mothers with negative test results are required, as well as a clear risk analysis of potential adverse events and their incidence r ates for the vaccines.  \n \nDr. Wester clarified that there is no data on new cases associated with delaying the birth dose \nrecommendation to one month of age.  \n Dr. Kulldorff asked whether the FDA has any information on this and suggested it may be fair to \nsay no.  \n \nDr. Hoeg  noted that the original clinical trial data from the 1980s, which appear on the product \nlabel, only included short -term follow -up of four to five days. She stated that this makes it \ndifficult to directly compare the safety risks of giving the vaccine at bi rth versus later in early \nchildhood. She asked how many of the studies presented by the CDC applied specifically to \nneonates and echoed earlier questions about follow -up and long -term safety data. She \nemphasized the need for more robust long- term data, particularly for infants of hepatitis B -\nnegative mothers, where the risk of infection is low, to weigh risks and benefits thoroughly.  \n Dr. Griffin addressed Dr. Stein’s earlier question about safety, noting that the CDC confirmed as \nearly as 2020 that no cases of hepatitis B transmission had been documented in school \nsettings, including elementary, middle, or high schools. She then referr ed to slide six, asking \nabout its source and what year it was from.  \n \nDr. Langer responded that multiple reports are stating the vaccine was safe, published in 1994, \n2002– 2004, 2012, and 2013.  \n \nDr. Griffin followed up, noting that in 2012, the Institute of Medicine reviewed hepatitis B vaccine \nsafety studies and concluded that evidence was inadequate to rule out the possibility that \nvaccination could lead to more than two dozen neurologic and aut oimmune disorders. She \nasked how this statement could be reconciled with describing the vaccine as safe and effective.  \n \n29 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  Dr. Wester added that, while the 2012 Institute of Medicine report stated there was insufficient \nevidence to accept or reject a causal relationship, an extensive body of literature has emerged \nover the past four decades. She noted that colleagues in the Im munization Safety Office would \nprovide additional data and are better positioned to respond in detail.  \n \nDr. Hibbeln stated that the question before the committee is whether the first dose of the hepatitis B vaccine should be delayed until one month of age for infants of hepatitis B -negative \nmothers. He said he was unclear if any safety or hazard data had been presented comparing \nvaccination before versus after one month. He asked why one month was chosen as the time \npoint, and whether data exist showing a greater risk of adverse effects before or after that age.  \n \nDr. Kulldorff noted that the current schedule recommends the second dose at one to two \nmonths of age, so delaying the first dose until one month would coincide with or come after the \nsecond dose. He suggested that the CDC is best suited to address the broader question of \nsafety.  \n \nDr. Hibbeln reiterated that the committee is being asked to vote on whether the first dose should \nbe delayed until at least one month of age for infants of negative mothers. He wondered if data \nshow that vaccination before one month carries a greater risk of adverse effects than after one \nmonth.  \n Dr. Malone added by asking whether there is data on a gradient of adverse events by age post -\nbirth, rather than only at the one- month time point, and whether risk decreases over time.  \nDr. Hibbeln agreed, emphasizing that if the committee is to vote on delaying the dose to one month, data are needed comparing adverse effects before and after that time.  \n Dr. Malone asked whether one month represents a distinct point of higher or lower risk, or if risk \nchanges more gradually over time, and whether data is available to clarify this.  \n \nDr. Kulldorff suggested the committee proceed to the safety presentation to address these \nquestions.  \n Dr. Pebsworth raised concern about data showing that 12– 16% of women do not receive \nprenatal care or hepatitis B screening. She questioned whether infants are being born in the \nU.S. without the mother’s hepatitis B status known, noting that a rapid test (s tat titer) should be \nable to provide results within one to two hours, which has important implications for infant care.  \nDr. Kulldorff responded that while in principle maternal status should always be known, the \nstandard test typically takes one to three days, so results may not be available before delivery.  \n \nDr. Pebsworth noted reports that a stat titer can provide results in one to two hours and asked if \nthis was accurate.  \n Dr. Griffin, speaking as an obstetrician- gynecologist, confirmed that the screening test can \nindeed be completed in under one hour, with results often available the same day. She added \nthat in the U.S., 98– 99% of women deliver in hospitals with laboratory capacity, and most \nreceive prenatal care. While approximately 7% of women lacked prenatal care in 2023 \n(according to the March of Dimes), hospitals routinely test for hepatitis B surface antigen at \ndelivery if prior results are unavailable, with results ty pically available within hours.  \n \nDr. Levi asked whether informed consent discussions with mothers include the opportunity to \ntest at delivery, assuming such talks take place as part of the decision to vaccinate the infant.  \n30 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.   \nDr. Griffin added that women typically remain in the hospital for at least 24 hours postpartum, \nallowing time for confirmatory testing and administration of infant vaccinations and HBIG, if \nneeded. She reflected that this raises an important question: are we vaccinating all newborns on \nday one to lower hepatitis B prevalence in high- risk populations, essentially asking babies to \nsolve an adult problem?  \n Dr. Langer explained that while a rapid hepatitis B test can sometimes be completed within 30 \nminutes to an hour, this assumes an ideal situation. Factors such as births outside hospitals, \nlaboratory backlogs, or the need for confirmatory testing can cause delays in results. He noted \nthat vaccination within 12 hours can avoid these risks and ensure timely protection. He added \nthat there are no data showing harm from vaccinating at birth compared to one month, but there \nare potential harms to delaying the dose, while the vaccination series would still be needed \nregardless.  \n \nDr. Kulldorff clarified that initial rapid testing can identify if a mother is negative within a short \ntime, while positive results require longer confirmatory testing.  \n \nDr. Griffin agreed, noting that the purpose of screening is to quickly identify those at risk, which \nallows for counseling and informed consent. She confirmed that in practice, results are available \nwithin a few hours, certainly within the first day, while the patient is still in the hospital.  \n Dr. Kulldorff added that for the committee’s decision, it is only necessary to know if the mother is negative. If the initial test is positive, the mother can be treated as positive without waiting for \nconfirmation.  \n Dr. Griffin agreed.  \n \nDr. Pollak noted that data suggest children not vaccinated in the perinatal period are much less \nlikely to return for vaccination later, with a hazard ratio of three. He emphasized that this \ndisproportionately affects single mothers, women of low socioeconomic status, persons of color, \nand high- risk groups such as Alaskans and First Nations. He requested data from the CDC on \nfollow- up and vaccination completion among infants who were not vaccinated at birth, such as \nthose weighing under 2,000 grams or those  with contraindications.  \n \nDr. Langer responded that there is an association between receiving the birth dose and \ncompleting the vaccine series on time. Infants who do not receive the birth dose are less likely \nto be vaccinated later.  \n \nDr. Pagano asked whether this association is confounded by parental choice, noting that some \nparents may refuse the birth dose and also decline later doses.  \n Dr. Langer agreed that the association does not imply causation. Parents who accept the birth \ndose are more likely to complete the series, but the underlying factor may be parental \nwillingness rather than the timing of the first dose.  \n \nDr. Levi noted that Canada’s provinces have a wide range of hepatitis B vaccination policies, \nwith first doses given as early as two months or as late as 11– 12 years. He asked whether \noutcomes differ by province and if delaying vaccination for infants of m others with negative test \nresults shows any impact on incidence.  \n \n31 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  Dr. Meissner emphasized that targeting select groups for vaccination has historically been less \neffective than broad recommendations. He noted the difficulty of identifying and vaccinating \nhigh- risk groups such as IV drug users, sex workers, and people experiencing homelessness. \nHe added that hepatitis B vaccination at birth, followed by the recommended series, likely \nprovides lifelong protection, as even if antibodies wane, cellular immunity produces an \nanamnestic response upon exposure. He argued that no data suggest that vaccination at two or \nthree months is safer than at birth, calling the vaccine extremely safe, with severe allergic \nreactions occurring in approximately one in a million doses. He questioned what would be \ngained by delaying the birth dose.  \n Dr. Hibbeln asked for clarification that hepatitis B can be transmitted to infants from sources \nother than the mother, noting that the virus survives on surfaces and can be spread by many \npeople.  \n \nDr. Levi responded that he was not aware of any documented data showing children becoming \ninfected through such mechanisms, although he acknowledged that he could have missed \nrelevant studies.  \n \nDr. Langer pointed out that during his presentation, he discussed  a study of U.S. -born children \nof immigrant mothers who tested negative at birth found that 7– 11% later tested positive for \nhepatitis B surface antigen, proving infections occurred postnatally. These children were too \nyoung for sexual or injection drug exposures, and their mothers were confirmed negative, so \ntransmission had to occur through casual or household contact. He added that the virus can survive on indoor surfaces for at least seven days, suppo rting the likelihood of community or \nhousehold transmission.  \n \nDr. Stein observed that the percentages cited for infections from non -maternal sources \nrepresent attributable risk rather than raw incidence counts. She emphasized that while still \nimportant, these numbers are not the same as direct incidence data.  \n \nDr. Hibbeln responded that his concern was not about exact numbers but about the framing of \nthe committee’s vote, which divides infants only by maternal hepatitis B status. He argued that \ninfections can occur from other household or community sources, and therefore, relying solely \non maternal status is insufficient. He stated that the most prudent approach would be to \nvaccinate as many children as possible to protect them broadly.  \n Dr. Griffin noted that informed consent discussions and social history intake are part of medical \npractice, where providers assess risk factors with patients.  \n \nDr. Hibbeln countered that if roughly half of infected people are unaware of their status, \ninformed consent discussions cannot reliably identify risk.  \n Dr. Griffin replied that physicians should still ask these questions and document the responses \nin electronic medical records, which could eventually be analyzed using advanced tools.  \n \nDr. Hibbeln responded that patients often cannot answer questions about their household \ninfection status if no one in the household has been tested.  \n Dr. Griffin reiterated that risk assessment must start somewhere.  \n \n32 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  Dr. Hibbeln concluded that if the goal is lifelong universal protection from a vaccine with very \nfew side effects, then limiting the recommendation based on maternal status alone is flawed, \nsince infection can occur from many sources throughout life.  \n \nDr. Meissner emphasized that medicine is not precise, and the risk for hepatitis B cannot be \nreliably determined through questioning alone, similar to HIV. He added that maternal testing is not perfect, with potential errors in transcription, assay perform ance, and distinguishing between \nhepatitis B surface antigen and surface antibody. He concluded that no system will ever identify \nall hepatitis B surface antigen– positive mothers at delivery with 100% accuracy.  \n The ACIP chair , Dr. Kulldorff,  requested a review of the 2004 study by Garly and colleagues \ntitled Hepatitis B vaccination associated with higher female than male mortality in Guinea -\nBissau: an observational study . The review included an assessment of non- specific effects of \nvaccination and findings from a rapid systematic review on mortality following hepatitis B \nvaccination.  \n \nNon-specific effects are defined as vaccine effects beyond protection against the target \npathogen, possibly due to changes in the immune system. These differ from adverse, cross -\nprotective, or indirect downstream effects. Clinical manifestations may include all -cause \nmortality, increased susceptibility to unrelated infections, or an increased risk of allergic and \nautoimmune diseases. Live attenuated and non- live vaccines may differ in these effects.  \n Garly and colleagues noted that while some studies have examined non- specific effects of \nvaccines on all -cause mortality, few have assessed hepatitis B vaccination specifically. Their \nstudy aimed to determine whether the hepatitis B vaccine was associated with sex -specific \ndifferences in mortality. The study was conducted within a trial of a two- dose standard measles \nvaccine in the Bandim Health Project surveillance system in Guinea- Bissau. Birth cohorts from \nMarch 1994 through February 2000 were included. Children born from March 1996 through \nFebruary 1997 were eligible to receive a hepatitis B vaccine at 7.5, 9, and 10.5 months of age. \nThe product used was a human plasma- derived vaccine, which is not licensed in the U.S.  [This \nraises questions about the applicability or relevance of the Garly et al. study to current U.S. \nhepatitis B immunization recommendations.]  \n \nA Review of the Safety of Hepatitis B Birth Dose Vaccination  \nDr. John Su (CDC/NCEZID)  \nDr. John Su (CDC/NCEZID) reviewed the safety of hepatitis B birth dose vaccination. The ACIP \nchair requested safety data on hepatitis B administration within 24 hours of birth from the CDC’s \nVaccine Safety Datalink (VSD) and the FDA’s Biologics Effectiveness and Safety System. The \nrequest included mild and serious adverse events, all -cause morbidity and mortality, short - and \nlong- term safety, outcomes of predetermined concern, and data- mining results, with findings \nreported both combined and stratified by s ex. \nTo address this, the CDC conducted a rapid systematic review of safety data on hepatitis B \nvaccination within 24 hours of birth. The key question was the safety of the vaccine when \nadministered in the first 30 days of life. To capture a broad range of studies, the review included \nall vaccines administered within 30 days, not just 24 hours. The search was performed on July \n31, 2025, using PICO (ST) criteria, and databases searched included Medline, EMBASE, \nCINAHL, and Cochrane.  \nInclusion criteria were newborn infants receiving hepatitis B vaccine at 30 days or less, \nrandomized controlled trials, observational studies, case series with 10 or more patients, and \n33 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  surveillance data. Outcomes included safety, adverse events, serious adverse events, and side \neffects. Exclusion criteria included non- English articles, animal studies, populations not \nreceiving the vaccine within 30 days or less, case series with fewer than 10 patients, clinical trial protocols, conference abstracts or posters, proceedings, or journal titles beginning with a \nnumber.  \nThe search identified 1,916 studies; after removing duplicates, 1,90 7 remained. Title and \nabstract screening excluded 1,678, and full -text review excluded another 158. Of the 71 studies \nleft, 20 either focused on the birth dose or reported results stratified by birth dose.  \nAmong these, five defined birth dose as administration within 24 hours of birth, including one VSD study. Four, including another VSD study, used terms such as “at birth,” “birth dose,” or \n“within 120 hours.” One study reported that 85% of infants received  hepatitis B on the day of \nbirth, with none vaccinated beyond 8 days. The remaining 11 studies allowed vaccination at any \ntime in the first month of life; although included in the systematic review provided to ACIP, they \nwere not discussed at the meeting.  \nStudies evaluated l ocal reactions. One randomized trial found 7.7% of infants experienced pain \nwith movement or pressure within 5 days of vaccination. Three studies reported pain or \nsoreness within 4 days for fewer than 10% of infants, with few severe cases. For injection site \nredness, one trial reported none within 5 days, while three studies reported 8– 20% within 4 \ndays, with no severe cases. For swelling, one trial reported a 7.7% rate within 5 days, while \nthree studies reported 0– 4% within 4 days, with no severe cases. One trial that evaluated local \nreactions as a combined outcome found 2.8% of infants experienced a reaction within the first week.  \nStudies also evaluated systemic reactions. Four studies on fever after hepatitis B vaccination \nwithin 24 hours of birth reported rates ranging from 0 to 5.6% during birth hospitalization up to \n21 days after birth. Among three studies where vaccination occu rred within 0 –5 days of birth, \nfever within 4 days of vaccination was reported for 0– 5.9% of newborns. Few cases were \nsevere.  \nFor anorexia or decreased appetite, one randomized trial of vaccination within 24 hours of birth \nreported no cases within 5 days of vaccination. In three studies where vaccination occurred \nwithin 5 days of birth, anorexia, feeding issues, or decreased appe tite within 4 days of \nvaccination were reported in 2.6– 16.5% of newborns, with few severe cases.  \nFor diarrhea or vomiting, one randomized trial of vaccination within 24 hours of birth reported no \ncases within 5 days of vaccination. Two additional studies where vaccination occurred within 5 \ndays of birth found diarrhea or vomiting within 3 days of vacc ination in 8.1 –11.7% and 4.4–\n22.3% of infants, respectively , with no severe cases . \nFor irritability or fussiness, one randomized trial of vaccination within 24 hours of birth reported \n11.5% of infants affected within 5 days of vaccination. Across three other studies where \nvaccination occurred within 5 days of birth, irritability, fussiness, or unusual crying within 4 days \nof vaccination was reported in 1.5– 22.1% of infants. Few cases were severe.  \nNo studies specifically evaluated sleep disturbance after vaccination within 24 hours of birth. \nHowever, three studies where vaccination occurred within 5 days of birth reported drowsiness or \nincreased sleep within 4 days of vaccination in 5.1– 32.4% of inf ants, and restlessness or \nreduced sleep within 3 days of vaccination in 16.9– 31.1% of infants. Few cases were severe.  \nA cohort study of vaccination within 24 hours of birth found no differences in care for allergic \nreactions between vaccinated and unvaccinated newborns within 21 days of life. No additional \nstudies evaluated allergic reactions in infants vaccinated within 5 days of birth.  \n34 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  One study evaluated infections after hepatitis B vaccination within 24 hours of birth. In this \ncohort study, vaccinated newborns were less likely to be evaluated for possible sepsis and less \nlikely to have a positive blood or cerebrospinal fluid culture. N o studies assessed infections \namong newborns vaccinated within 5 days of birth.  \nTwo studies examined other adverse events. In one cohort, hepatitis B vaccination within 24 \nhours of birth did not increase the risk of seizures or other neurologic disorders. In another cohort of preterm infants identified through Australia’s surveillance system, hepatitis B \nvaccination appeared to have a slight protective effect against bronchopulmonary dysplasia. In \nan additional cohort where vaccination was administered within 5 days of birth, one serious \nadverse event was reported: a cough that require d hospitalization 37 days after vaccination, \nwhich the investigators deemed unrelated.  \nOne study evaluated all -cause mortality after hepatitis B vaccination within 24 hours of birth. In \na cohort of preterm infants in Australia, there were no differences in mortality within 3 months of \nlife between vaccinated and unvaccinated infants. Two studies assessed mortality after hepatitis \nB vaccination within 8 days of birth. In one randomized trial, no deaths occurred during a 7-\nmonth follow -up period among infants who received the hepatitis B vaccine within 4 days of \nbirth. In a large US cohort study including more than 350,000 live births between 1993 and 1998, 1,363 neonatal deaths within 29 days were identified. Of these, 72 (5%) occurred in \ninfants who received the hepatitis B vaccine at birth. No significant differences were observed \nbetween vac cinated and unvaccinated newborns in rates of expected or unexpected deaths, \nincluding deaths due to sudden infant death syndrome.  \nLimitations of this rapid systematic review include the small number of studies on hepatitis B \nvaccination within 24 hours, inconsistent reporting of timing, and heterogeneous methods that \nprevented meta- analysis. Most studies have focused only on short -term outcomes, such as \nreactogenicity or mortality within 30 days, while long- term outcomes have not been captured.  \nDr. Su concluded that the review found no increased risk for allergic reactions, mortality, sudden \ninfant death syndrome, seizures, or other neurologic disease. Compared to infants who did not \nreceive the birth dose, those who did had lower risks of invasi ve diagnostic procedures, positive \ncultures, and bronchopulmonary dysplasia. Results on short -term reactogenicity varied across \nstudies.  \nNon-specific effects following hepatitis B vaccination  \nDr. John Su (CDC/NCEZID)  \nDr. John Su (CDC/NCEZID) shared data on non -specific effects following hepatitis B \nvaccination. The ACIP chair requested that the Immunization Safety Office present the 2004 \nstudy by Garly and colleagues, “Hepatitis B vaccination associated with higher female than male \nmortality in Guinea- Bissau : an observational study .” In addition, Dr. Su presented the results of \na rapid systematic review of non -specific effects (NSEs) of Hepatitis B vaccination, including \ndata on mortality after hepatitis B vaccination. NSEs are effects beyond protection against the \ntarget pathogen, potentially  mediated by immune system changes; they are distinct from \nadverse, cross -protective, or indirect effects , and may manifest as changes in all -cause \nmortality, unrelated infections, or risk of allergic and autoimmune diseases. Live- attenuated and \nnon-live vaccines may differ in their NSEs.  \nThe Garly 2004 study aimed to assess whether hepatitis B vaccination is associated with sex -\nspecific differences in mortality. It was conducted within a two- dose standard measles vaccine \ntrial embedded in the Bandim Health Project surveillance system in Guinea- Bissau. Birth \ncohorts from March 1994 through February 2000 were enrolled. Children born from March 1996 \n35 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  to February 1997 were eligible for the hepatitis B vaccine at 7.5, 9, and 10.5 months of age. The \nhepatitis B product used was a human plasma– derived vaccine not licensed for use in the U.S.  \nDr. Su summarized three mortality comparisons. First, across birth cohorts, mortality at 7.5– 12 \nmonths was compared with mortality at 1.5– 7.5 months; overall, the rate ratio was 0.97, but in \nthe year when most children received the hepatitis B vaccine at 7.5 months, it was 1.62 (95% \nCI, 1.09 –2.41). Second, among 5,441 children in the two-dose measles vaccine trial , the \nmortality rate ratio at 7.5 –12 months was 1.81 (95% CI, 1.19– 2.75) for hepatitis B -vaccinated \nchildren compared to unvaccinated children. Third, among measles -vaccinated children, the \nfemale- to-male mortality rate ratio was 1.66 (95% CI 0.80– 3.45) through 12 months of age for \nthose who also received hepatitis B vaccine; through 24 months of age, the rate ratio was 2.20 \n(95% CI 1.07– 4.54) with both vaccines versus 0.96 (95% CI 0.70 –1.32) with measles vaccine \nonly. The study authors (Garly, et al.)  concluded these analyses suggest changes in mortality \npatterns after hepatitis B vaccine introduction in a high- mortality setting, with a stronger eff ect \namong females, raising the possibility of sex -differential non- specific effects.  \nThese analyses were not planned when the trial was designed, and the study was not randomized, so unbiased comparisons over the same time period could not be ensured. \nHepatitis B vaccine was administered at 7.5, 9, and 10– 10.5 months in this study; therefo re, the \neffects may differ when given at birth or alongside other vaccines, such as BCG. A higher \nfemale- to-male mortality ratio could also reflect reduced male mortality.  \nA rapid systematic review was conducted to [address the question, “W hat are the non -specific \neffects of hepatitis B -containing vaccines administered in childhood?”]  The review included \nstudies published through August 20, 2025, among infants and children up to six years of age \nwho received either a monovalent hepatitis B vaccine or a combined vaccine, compared with \nany or no comparator. Outcomes included non -specific effects ; studies in any setting and of any \nduration of follow up were included for review.  \nInclusion criteria allowed for clinical trials, observational studies, surveillance reports, and \nsystematic reviews. Eligible populations included infants and children younger than seven years \nof age who had received a hepatitis B vaccine, either alone or in combination. Included s tudies  \nevaluated outcomes related to non -specific effects. Exclusion criteria ruled out case reports and \ncase series, narrative reviews, animal studies, children older than seven years, adults, vaccines other than hepatitis B, an d studies assessing outcomes outside of non -specific effects.  \nA total of 2,068 studies were identified. After keyword screening, 237 remained; however, 221 were excluded during the title and abstract review. Sixteen full texts were reviewed, and eight \nwere excluded, resulting in eight studies included in the final review.  \nOf the eight included studies, four evaluated the hepatitis B vaccine as part of a pentavalent \nvaccine and four evaluated the monovalent vaccine. Seven were cohort studies and one was a \nnested case series. Six studies were conducted in low - and middle- income countries and two in \nhigh- income countries. Four studies evaluated mortality, five assessed sex -differential mortality, \nand one examined another non -specific effect.  \nAmong the three studies that evaluated mortality, two cohort studies in high- income countries \nfound no association between hepatitis B vaccination and all -cause mortality. A cohort study \nconducted in a low - to middle- income country found an increased risk of all -cause mortality \nfollowing vaccination.  \nEvidence regarding sex -specific mortality was inconsistent. One study observed both no \ndifference and an increase in the female- to-male mortality ratio. Another study suggested that \nthere is no difference in mortality by sex.  \n36 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  One cohort study in a high- income country evaluated cancer -related and cardiovascular -related \nmortality and found no effect of hepatitis B vaccination on these outcomes.  \nOverall, there are few studies available to inform the non -specific effects of hepatitis B \nvaccination in children. Studies in high- income countries found no association with all -cause \nmortality, while one study in a low - to middle -income country suggested  an increased risk. \nEvidence regarding sex -specific mortality was inconsistent.  \nDr. Su concluded that non- specific effects may vary in settings with different background  \nmortality rates and infectious diseases burden . These effects may not be generalizable across \nimmunization programs and might also vary depending on the specific vaccine product used. \nFor example, Heppacine is not licensed for use in the United States, where the hepatitis B \nvaccine is administered earlier and often in combination with other routine vaccines. The \nbiological, molecular, and immunologic mechanisms underlying non- specific effects are not fully \nunderstood. In particular, the timing between vaccination and the onset of any non- specific \neffect, as well as the duration of such effects, remains uncertain. The duration of a vaccine’s \nnon-specific effect may also be complicated by subsequent vaccinations received.  \nDiscussion  \nRick Haupt (Merck), head of the ID Vaccines Medical and Scientific Affairs group, shared a manufacturer statement. He referred to Dr. Langer’s presentation, which highlighted the \nrationale and importance of routine newborn vaccination as a crucial public health strategy to \nprevent chronic viral hepatitis and its severe long- term consequences. He noted that the risk of \ndeveloping chronic hepatitis B infection is strongly age- dependent, with up to 90% of infants \ninfected at birth progressing to chronic infect ion, which can lead to chronic liver disease and \nliver cancer. Transmission may occur from an infected mother or through close contact with an \ninfected family member. He emphasized that the CDC has reported that one in two people is \nunaware of their infect ion status. He stated that Merck’s Hep B vaccine, Mercivovax HB, was \nfirst approved in the United States in 1986 and has been a foundation of hepatitis B prevention, with more than 330 million doses distributed between 1990 and 2019. Universal infant and \nchildhood vaccination for hepatitis B has resulted in a 99% decline in reported cases of acute \nhepatitis B among children, adolescents, and young adults under 19 years of age. He concluded \nthat vaccines remain the best defense against many serious diseases,  with strong scientific \nevidence supporting their use. He cautioned that reconsidering newborn hepatitis B vaccination \non the established schedule would pose a serious risk to the health of children and the public \nand could lead to a resurgence of preventable infectious diseases.  \nAyman Chit (Sanofi), head of the medical affairs department at Sanofi Vaccines in the United \nStates, shared a manufacturer statement. He emphasized that the company’s top priority is \nensuring access to safe and effective vaccines. He stated that administra tion of hepatitis B dose \nearly in life remains the most effective option for preventing hepatitis B infection in infants and children. He noted that scientific evidence strongly supports the safety of both hepatitis B \nvaccines and combination vaccines that  include hepatitis B, and that these vaccines are \ncontinuously monitored by manufacturers, public health agencies, and regulators before and after approval. He cautioned that changes to the hepatitis B infant schedule could disrupt \nimplementation and reduc e the benefits provided by combination vaccines. Combination \nvaccines lessen the number of injections infants receive, improve provider workflow, and help \nlimit administration errors. If recommendations change for one component, providers will need \nto stoc k both single- antigen and combination products, creating challenges with supply, storage, \nhandling, administration, and documentation. He warned that delaying the hepatitis B birth dose \nputs infants at risk of infection and reduces families’ options to use combination vaccines. He \nadded that such a change would likely cause significant supply disruptions lasting a year or \n37 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  longer due to the production lead time, affecting not only combination vaccines but also single-\nantigen products such as Hib and polio. He concluded that maintaining current \nrecommendations for hepatitis B vaccination is critical to ensure infants remain protected early \nin life, high -risk infants are not missed, and families continue to have access to widely available \ncombination vaccines that protect against multiple vaccine- preventable diseases.  \nDr. Griffin stated that regarding the first presentation, she wanted to know how many of the \nstudies were based on thimerosal -containing vaccination.  \n \nDr. Hause from the Immunization Safety Office stated that she did not have the number on hand \nbut could provide it after a brief review.  \n \nDr. Griffin stated that she asked because there has not been a hepatitis B vaccine containing \nthimerosal since 2001. She noted that she counted about five or six such studies and \nquestioned the rationale for including them. She asked if any of the studies were designed to \nhave safety as the primary endpoint, since many appeared to focus on immunogenicity.  \n \nDr. Su stated that safety was part of the studies but deferred to colleagues for clarification on \nwhether safety was the primary endpoint.  \n \nDr. Hause stated that several studies evaluated safety as the primary endpoint and that several \nrandomized controlled trials also included safety as a secondary endpoint.  \n Dr. Griffin asked how many studies were specifically designed with safety as the outcome.  \n \nDr. Hause stated that three studies specifically examined safety as an outcome.  \n Dr. Griffin clarified that this meant three out of twenty studies and requested to go back to slide \n23 from the first presentation.  \n \nDr. Hause clarified that three out of nine studies were presented in the slides.  \n \nDr. Griffin thanked her and requested that slide 23 be pulled up, noting it was a summary slide. \nShe inquired about the commentary on bronchopulmonary dysplasia, pointing out that she had \nfound one article, Morgan et al. (2025), and questioned whether that  was the only study used in \nthe summary.  \n \nDr. Hause confirmed that it was.  \n \nDr. Griffin expressed concern, stating that the authors of that study declared seven significant \nlimitations. She highlighted the inability to control for confounding factors, including infections \nand respiratory support, and noted that clinician perception of newborn stability could also \ninfluence vaccination decisions. She emphasized that withholding vaccination in unwell infants \ncould confound results and underestimate risks. She then asked if there were any other studies \nshowing findings related to bronchopulmonary dysplasia.  \n \nDr. Hause stated that the study in question was included because it met the criteria for \nsystematic review. She noted that no other studies identified in the review met the criteria with \nbronchopulmonary dysplasia as the outcome.  \n \n38 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  Dr. Pebsworth referred to slide 15 from the first presentation, which evaluated systemic \nreactions such as irritability, fussiness, or crying, noting rates of 20– 22% among participants. \nShe stated that these rates seemed very high, particularly since they may be early symptoms of \nneurologic problems requiring long- term follow -up, which is lacking in the available data. She \ncommented on the Institute of Medicine (IOM) reports, clarifying that the IOM did not conclude \nthat the hepatitis B vaccine was safe but  instead reviewed multiple conditions and assessed the \nweight of epidemiologic evidence, mechanistic evidence, and causality conclusions. She noted \nthat the IOM reviewed three reports on hepatitis B between 1994 and 2012 and concluded that \nthe evidence was  inadequate to accept or reject a causal relationship between the hepatitis B \nvaccine and conditions such as encephalitis and encephalopathy. Additionally, the IOM found that of 26 conditions reviewed, this same conclusion applied to at least 24 of them. S he listed \nseveral of the conditions considered in the IOM report, including encephalitis, encephalopathy, \nseizures, acute disseminated encephalomyelitis, transverse myelitis, optic neuritis, \nneuromyelitis Optica, multiple sclerosis onset and relapse, Guill ain-Barré syndrome, chronic \ninflammatory demyelinating polyneuropathy, lupus, vasculitis, polyarteritis nodosa, psoriatic \narthritis, and reactive arthritis, emphasizing that the IOM conclusions indicated uncertainty \nrather than confirmation of safety. She also referenced a 2024 systematic review on the safety \nof hepatitis B vaccines in preterm infants, noting that it found no publications on the timing of the \nbirth dose and adverse events, and that reporting was limited to short -term outcomes, \nhighlighting that research on the safety of hepatitis B vaccination in preterm infants within seven \ndays of birth, especially regarding long- term morbidity, is lacking. She further referenced a 2016 \nmouse model study showing that neonatal hepatitis B vaccination impair ed behavior and \nneurogenesis in early adulthood, with the conclusion that vaccination impaired hippocampal LTP and neurogenesis and that the possible mechanism involved alterations in the brain \nneuroimmune milieu from a systemic TH2 bias. She concluded that there are gaps in knowledge \nabout the effects of hepatitis B vaccination on very young infants and stated that concluding the vaccine is safe may be premature.  \n \nDr. Levi stated that the Garly paper was one of the most well -done examples of a natural \nrandomized experiment. He recalled that children vaccinated between seven and a half months \nand 12 months showed almost 80% higher mortality compared to other cohorts.  He asked why \nthis result was not discussed and whether it was because the focus was on earlier age groups.  \n \nDr. Su asked if Dr. Levi was referring to the Garly paper and clarified that he was reviewing his \nslides. [This finding was presented on slide nine. In comparison two, a mong children enrolled in \nthe measles vaccine trial, compared with HBV -unvaccinated children, the mortality rate ratio for \nchildren 7.5 -12 months of age from the HBV -vaccinated cohort was 1.81 (95% CI 1.19, 2.75). ] \n \nDr. Kulldorff stated that while Dr. Su was reviewing, the discussion could move to Dr. Milhoan.  \n \nDr. Milhoan stated that the neonatal period is a very sacred time for intervention and that \nmedical decisions at this stage must be approached with caution, as any changes in the baby’s \ncondition lead to invasive evaluations and treatments. He explained that risks are higher for \nprocedures such as anesthesia and surgery in newborns, particularly premature infants. He \nemphasized that while public health prioritizes populations, it does not always prioritize \nindividual patients, and decisions for the most vul nerable must be made with utmost caution. He \nquestioned whether seroconversion rates had been evaluated starting at two months rather than at birth, pointing out that while seroconversion occurs at a rate of 26% at birth, higher levels are \nachieved after s ubsequent doses, with approximately 95% after the third dose. He suggested \nthat beginning vaccination later might reduce the number of doses required and decrease risk, \n39 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  since every injection carries some risk. He asked whether T -cell immunity, which may be more \nrobust early in life, had been considered as part of the vaccine response.  \n \nDr. Levi added that seroconversion rates were 25% after the first dose, 63% after the second \ndose, and 95% after the third dose.  \n \nDr. Milhoan stated that if vaccination began at two months and continued at six months, the \nseroconversion rate should be examined to see whether earlier vaccination unnecessarily adds \ndoses. He clarified that he was not advocating against vaccination but instead suggesting that \nrisks could be reduced if the schedule were reevaluated. He also referred to slide 23, which \nsummarized death outcomes, stating that rather than showing a positive effect of hepatitis B \nvaccination, the data reflected selection bias : healthier children were more likely to be \nvaccinated early, leading to more favorable outcomes unrelated to the vaccine. He noted that \nthis reflected selection rather than a true protective effect.  \n \nDr. Kulldorff added that this phenomenon is called “healthy vaccination.”  \n Dr. Milhoan continued by noting that while outcomes reported included allergic reactions and all -\ncause mortality, other important outcomes were missing. He asked whether data were available \non whether infants required advanced care or were coded.  \n Dr. Su stated that he did not have that information and referred to the investigators of the paper.  \n \nDr. Blackburn asked how the language was decided to recommend vaccination at one month \nrather than two months, noting that most other countries recommend delaying for hepatitis B -\nnegative mothers. She stated that while she could see justification for this approach, she was \nconcerned when reviewing safety data about the risks of fever and poor feeding. She explained \nthat any fever in a newborn under 28 days is considered a medical emergency and typically \nprompts a full sepsis workup, spinal tap, hospitalizat ion, and empiric IV antibiotics. She added \nthat, as a parent with firsthand experience, early feeding is essential to successful \nbreastfeeding, and a decreased appetite in the early days of life can have a significant impact. \nShe emphasized that these risk s should be taken into consideration when weighing the benefits \nand harms.  \n \nDr. Kulldorff  responded that the decision was related to the fact that the second dose in the U.S. \nis recommended between one and two months of age, and he noted that he had been personally involved in discussions about the recommendation with CDC staff.  \n \nDr. Malone stated that while concerns about irritability, fever, and poor feeding may or may not \nbe indicators of neurological problems, it is important not to base votes or recommendations on \nspeculation. He emphasized that decisions should be based on da ta reflecting concrete risks or \nbenefits, rather than hypothetical clinical outcomes for which there is no evidence. He referenced the IOM findings, noting that although neurological outcomes had been considered, \nthere was no evidence to make a causal link  either for or against such conditions. He concluded \nthat the committee should not extend beyond the data when making determinations.  \n Dr. Meissner stated that there is no association or lack of association between the hepatitis B \nvaccine and bronchopulmonary dysplasia (BPD). He explained that BPD occurs in preterm \nbabies who are typically more than 10 weeks early, weigh less than two pounds, and are often \nmechanically ventilated. He emphasized that the condition results from barotrauma or trauma \nassociated with mechanical ventilation, making it biologically implausible for the hepatitis B \n40 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  vaccine to have any relationship with BPD, and he advised not placing too much concern there. \nHe then referred to the Garly study and asked for clarification, noting that Dr. Su had given \nexcellent presentations, and inquiring whether the vaccine in that s tudy was a human plasma–\nderived hepatitis B vaccine.  \n \nDr. Su stated that the Garly paper involved a plasma- derived hepatitis B vaccine.  \n \nDr. Meissner explained that the original hepatitis B vaccine was produced from the plasma of \npeople with chronic hepatitis B, which was then inactivated by heat or chemical treatment to \nprevent infection before being concentrated. He emphasized that this v accine was very different \nfrom the current vaccine, which is made using cloned hepatitis B surface antigen in yeast, \nresulting in a pure and well -defined product. He stated that the vaccine used in the Garly study \nwas not the same as the modern vaccine and  therefore should not be emphasized in current \ndiscussions. He further noted that changing the recommendation for neonatal administration of \nthe hepatitis B vaccine would increase the risk of harm without evidence of benefit, as fewer \nchildren would comple te the full hepatitis B vaccine series if initiation were delayed. He noted \nthat beginning vaccination in the hospital ensures that at least the first dose is administered. He stressed that there is no evidence to suggest that the vaccine becomes less safe  over time, that \nit is extremely safe and pure, and that changing the recommendation could create unjustified \npublic doubts. He concluded that there is no evidence of harm from administering the neonatal \nvaccine, either from presentations or from his review of the literature and expressed concern \nabout changing the recommendation.  \n \nDr. Malone stated that he agreed with Dr. Meissner that the BPD signal was artifactual. He \nnoted that the reported improvement in risk of BPD in the paper likely reflects healthy vaccine \nbias or reporting bias. He concurred that the Garly study involved the historic plasma -derived \nvaccine, which was associated with adverse events not relevant to the modern product. He \nnoted that the question of changing recommendations also raised moral and ethical \nconsiderations. He added that what he had not heard was clear data on the risks to premature \ninfants, and he asked for clarification on whether there are differences in safety, effectiveness, \nimmunogenicity, or seroconversion between premature infants and healthy newborns.  \n Dr. Su responded that he could speak about the safety aspects, noting that the data were \nlimited to the studies that met the inclusion criteria. He stated that a few of those studies \naddressed adverse events in premature infants, but deferred to other expe rts in the room for \nfurther knowledge on that topic.   \nDr. Hause stated that only one study met the criteria for the systematic review that looked at \npremature infants, which was the Morgan study with the outcome of bronchopulmonary \ndysplasia. She added that only one study specifically listed the use of a thim erosal -containing \nhepatitis B vaccine.  \n \nDr. Malone stated that, based on the discussion, there appeared to be insufficient data to \nassess safety, immunogenicity, and seroconversion in premature infants, and he asked for \nconfirmation.  \n \nDr. Langer responded that under the current recommendation, newborns weighing less than \n2,000 grams who are born to hepatitis B -negative mothers should not be vaccinated at birth. He \nclarified that the recommendation is to wait for one month.  \n Dr. Milhoan asked whether the one month referred to gestational age or corrected age.  \n41 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.   \nDr. Langer stated that he would defer to colleagues on that detail.  \n Dr. Meissner stated that the recommendation is to wait until one month of age or until discharge \nfrom the neonatal unit to home.  \n \nDr. Kulldorff confirmed that this was correct.  \n \nDr. Stein stated that her question concerned the extensive data provided in the summary \ndocument, which included many detailed study summaries. She asked for clarification on what \nis meant by “low confidence.”  \n \nDr. Hause explained that each study was reviewed for risk of bias and graded using \nstandardized tools for systematic review. She stated that results varied by study, particularly in \nrelation to study design, and that details could be provided to the commit tee after the meeting.  \n \nDr. Stein added that several studies had shown potential long- term risks, but that bias might \ninfluence these findings, and she had not reviewed them in detail.  \n \nDr. Hause stated that there are studies examining long- term outcomes in the larger systematic \nreview. However , they were not included in the presentation because they did not assess \nhepatitis B doses given within the first 24 hours of life, which was the specific request of ACIP. \nShe noted that those studies could be provided to the committee separately.  \n \nDr. Middleman asked two questions. First, she asked what problem exists in the current \nschedule that prompted the discussion, noting that the hepatitis B immunization schedule has been highly successful, with a favorable benefit -to-risk ratio. She emphasiz ed that while there \nare always risks and benefits to weigh, risk -based approaches to vaccination have historically \nnot been effective across multiple vaccines. She expressed uncertainty about what specific \nissue had led to reopening the discussion. Second,  she commented on the exclusion of liaison \nmembers from working groups, noting that liaison members bring extensive knowledge and \nrepresent patients. She emphasized that their perspectives on issues such as adjuvants or \nneonatal vaccination thresholds add value to vaccine recommendations. She asked how liaison \nmembers might be included again to contribute on behalf of their patients and their expertise.  \n Dr. Kulldorff responded to the second question, explaining that the exclusion of liaison members \nfrom working groups was a CDC -wide Federal Advisory Committee Act (FACA) policy, which \nwas outside the control of ACIP. He stated that in the past, ACIP had no t been following this \nrequirement, and the change was necessary to align with FACA rules. He agreed that liaison member input is valuable, but clarified that outside experts, including those affiliated with \norganizations represented by liaison members, are included in working groups. He explained \nthat these experts serve as individuals rather than representatives of their organizations. He concluded that while outside expertise is incorporated, ACIP must comply with FACA policy \nregarding liaison members. Regarding the first question, he invited Dr. Levi to respond.  \n \nDr. Levi shared two personal experiences. He stated that he had received the hepatitis B \nvaccine as an adult before traveling to high- risk areas, and that all six of his children received \nthe vaccine on the first day of life without prior discussion or inf ormed consent. He suggested \nthat this illustrates how often informed consent may not occur for this vaccine. He expressed \nconcern about the frequent claim that “there is no evidence of harm,” emphasizing that the \nrelevant question is whether there is evidence of no harm, particularly for a vaccine \n42 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  administered on the first day of life to healthy infants. He argued that the risk of not vaccinating \non the first day of life is likely negligible during the first several months or even years. He \nquestioned why there have been no large, long- term randomiz ed clinical trials (RCTs) to resolve \nthe debate about safety, stating that the lack of such trials reflects broader problems with the \nmedical system and vaccine research. He reiterated his belief that the hepatitis B vaccine is life -\nsaving and essential fo r high- risk infants and adults. Still, he stated that arguing from weak \nevidence undermines trust and is not a scientific approach. He described the absence of long-term RCTs as the “elephant in the room.”  \n \nDr. Fryhofer, a general internal medicine physician in full -time practice and the American \nMedical Association (AMA) liaison. She disclosed that she had received the hepatitis B vaccine \nas a medical student after rotating through a hepatitis ward, where she saw severely ill patients. \nShe stated she was thankful the vaccine exists. She explained that the hepatitis B virus \nprimarily affects the liver and can cause chronic infection, cirrhosis, liver cancer, and death. She \nnoted that the virus can be transmitt ed in utero and through bloodborne routes, and that when \ntransmission occurs in utero, 90% of infants remain chronically infected. She highlighted that \nadministering the hepatitis B vaccine at birth has nearly eliminated perinatal hepatitis B, with \nonly 13 cases reported in 2022. She emphasized that the birth dose is safe and effective and \nstated that the AMA strongly urges ACIP to maintain the recommendation for newborn \nvaccination.  \n Dr. Munoz, a pediatric infectious diseases physician specializing in transplant infectious \ndiseases at an institution that performs the largest number of pediatric liver transplants in the country, and a clinician- investigator with many years of vaccine re search experience, asked why \nthe hepatitis B vaccine recommendation is under review and whether there is a specific reason \nfor considering a change. She emphasized that the data presented show significant declines in \nhepatitis B incidence and long- term con sequences due to vaccination, both in children and \nadults, and that this progress is directly attributable to vaccination. She noted that the vaccine \nstrategy is safe, effective, and widely implemented globally, with U.S. data suggesting that \nhepatitis B c ould be eliminated through continued vaccination. She emphasized that risk -based \nstrategies are imperfect due to potential false- negative tests, inadequate prenatal care, limited \naccess, and gaps in understanding vaccine benefits. She warned that changing the \nrecommendation could reintroduce vertical transmission or leave adolescents unprotected, \nresulting in severe disease. She concluded that the vaccine is very safe, that those at greatest \nrisk would be most affected by changes. She urged the committee to maintain the current \nrecommendation to protect both individuals and the broader public, especially the most vulnerable.  \n \nDr. Paulsen, a liaison with the Pediatric Infectious Disease Society, stated that he agreed with \nthe concerns raised by ACIP members regarding the protection of children in the newborn \nperiod, which he described as a sensitive time. He noted that the hepat itis B birth dose \nultimately comes down to weighing risks and benefits. He emphasized that CDC presentations consistently showed the risks to be low and that the data specifically focused on the infant birth \ndose. He highlighted that fever in infants often  prompts a sepsis workup, including a lumbar \npuncture, but that CDC data showed the risk of requiring such a workup was lower in infants \nwho received the hepatitis B vaccine within 24 hours. He concluded that the benefit is avoiding \na lifelong, chronic, vaccine -preventable infection. While in an ideal world, all maternal infections \nwould be known and properly managed, public policy must be based on what protects the population broadly. He urged ACIP to continue preventing infection in children rather than \ntreating hepatitis B as an adult problem.  \n \n43 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  Dr. Buchanan, representing the National Association of Pediatric Nurse Practitioners, stated that \nshe wanted to echo and reiterate the safety of the vaccine. She shared her personal experience \ncaring for many children and administering the hepatitis B vacc ine in clinics, emphasizing that \nunder her care, no child had been harmed by the vaccine. She added that while members were \nsharing personal accounts, she also wanted to raise the broader question many were asking: \nwhy the vaccine’s safety is being reconsi dered now, given its well -established record of safety \nover several decades.  \n \nDr. Hayes, representing the American College of Nurse Midwives, stated that in most facilities, \nwhen a woman in labor signs the consent form, it includes consent for the hepatitis B vaccine \ndose. She explained that in her experience, the process functions as a universal consent, with \nthe option for refusal, meaning parents can decline the hepatitis B vaccine if they choose.  \n \nDr. Jshlay, a family physician who provides prenatal care, stated that hepatitis B screening is \noften done early in pregnancy, but that risk can change over time. She noted that the growing \nuninsured population, including those losing commercial or Medicai d coverage, increases the \nlikelihood of patients presenting without prenatal care at delivery, making it difficult to obtain timely test results. She added that many patients do not disclose risk information due to \nembarrassment or stigma. She emphasized t hat if vaccination approaches differ based on risk, \nmothers may be stigmatized; universal vaccination avoids this by ensuring all families are treated equally, which supports equity in care.  \n Dr. Hopkins stated that his greatest concerns related to equity and lack of knowledge. He noted that about 50% of adults in the population, including those presenting for delivery, do not know \ntheir hepatitis B status, and congenital hepatitis B infections  continue to occur. He stated that \nremoving the birth dose would increase population risk and that equity must remain central in the evidence -to-recommendation framework. He added that while additional long- term data may \nbe needed, as Dr. Levi suggested, i t would not make sense to remove a successful intervention \nwhile waiting for such data. He concluded that decisions should be made with care and based \non the full body of evidence, rather than being rushed.  \n \nDr. Malone stated that the central question repeatedly raised, particularly by liaison \nrepresentatives , is why the issue of deferring the hepatitis B birth dose to one month is being \nconsidered now, given that no clear safety signal has been detected. He suggested that the \ntiming appears to be less tied to scientific evidence and more to public trust, noti ng that a \nsignificant portion of the U.S. population has concerns about vaccine policy, mandates, and the administration of the hepatitis B vaccine at bir th without meaningful informed consent. He \nobserved that the birth setting is often stressful and overwhelming, making it difficult for parents \nto process information and provide truly informed consent, and that some parents feel the \nvaccine is administered unilaterally by medical professionals. He linked these concerns to \nbroader declines in public trust in vaccines and public health following the COVID -19 pandemic. \nHe referenced Sweden as an example where, despite the absence of vaccine mandates and a hepatitis B birth dose, vaccine uptake is high and infectious disease outcomes are strong, \nattributing this to greater public trust in Swedish public health. He concluded that the issue \nbefore ACIP is not driven by a safety signal but by public discomfort and  mistrust, and that while \ndata presented may provide reassurance, many concerns will likely persist. He clarified that he \nhad no direct communication with CDC or HHS leadership on this issue and was offering his \nperspective based on public opinion trends.  \n \n44 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  Proposed recommendations and discussion  \nDr. Martin Kulldorff (ACIP Chair)  \nProposed Recommendation #1:  \n All pregnant women should be tested for hepatitis B infection.  \nProposed Recommendation #2:  \n The pediatric vaccine schedule should be updated to reflect the following change:  \n If a mother tests HBsAG -negative:  \n-The first dose of the Hepatitis B vaccine is not given until the child is at least one \nmonth old.  \n-Infants may receive a dose of Hepatitis B vaccine before one month, according \nto individual based decision- making.*  \n*Also referred to as shared clinical decision- making.  \nDr. Kulldorff clarified that if parents choose to have the first dose administered on day one or at \nany time before one month, even if the mother tests negative, the dose will be covered by CMS, \nMedicare, Medicaid, and other health insurance providers.  \nVFC Resolution Update: Hepatitis B Vaccines  \nJeanne Santoli (CDC/NCIRD)  \nJeanne Santoli (CDC/NCIRD) presented on the resolution with all revisions from the previously \napproved resolution shown in red. The purpose of the update is to update the Recommended \nVaccination Schedule and Intervals section to align with the proposed  recommendations \nregarding the hepatitis B birth dose  under discussion today by ACIP . She reviewed the changes \nto the infant vaccination table, clarifying that for infants weighing at least 2,000 grams and born \nto mothers who are hepatitis B surface antigen– negative, the timing of the first dose was  revised  \nto 1-2 months and the second dose was adjusted to 3-4 months  for infants receiving single \nantigen vaccine. For infants weighing less than 2,000 grams and born to hepatitis B surface \nantigen– negative mothers, the timing was the same. She explained a  revised footnote stating \nthat only the single- antigen hepatitis B vaccine can be given at less than or equal to six weeks \nof age, replacing prior language that referred to birth. She highlighted two new footnotes \nreflecting individual -based or shared clinical decision- making for both ≥2,000- gram and <2,000-\ngram infants with hepatitis B surface antigen– negative mothers, allowing for one dose to be \nadministered before one month  of age. She confirmed that there were no changes to children’s \nvaccination schedule table , related table notes, interrupted schedules, minimum dosing \nintervals, revaccination guidance, recommended dosage, contraindications, or precautions. She closed by noting the standard clause that new guidance published within six months would be \nincorporated by reference, which was also unchanged.  \nVotes \nDiscussion  \nDr. Hayes suggested revising the wording slightly to specify the antigen test rather than the \nantibody test, to provide clearer guidance for clinicians.  \nDr. Kulldorff agreed that this was a good suggestion and stated that CDC colleagues could refine the exact language to ensure the proper test was clearly identified.  \n \nVote: Hepatitis B Vaccine Vote #1  \nDr. Martin Kulldorff (ACIP Chair)  read the following proposed ACIP voting language for the  \nvaccine into the record:  \n45 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.   \nAll pregnant women should be tested for hepatitis B infection.  \n \n \nMotion/Vote: Hepatitis B  Vaccine   \n \nDr. Levi motioned to approve the recommended voting language, stating,  “All pregnant women \nshould be tested for hepatitis B infection. ” Dr. Griffin seconded the motion. No COIs were \ndeclared. The motion carried with 12 votes in favor, 0 votes opposed, and 0 abstentions. The \ndisposition of the vote was as follows:  \n \n    12 Favored:  Malone, Hibbeln, Pagano, Milhoan, Blackburn, Griffin, Stein, Pollak, \nPebsworth, Levi, Meissner, Kulldorff  \n    0 Opposed:    \n    0 Abstained:   \n \nDr. Pebsworth stated that after reviewing the CDC’s presentation, specifically slide 18 on the \nglobal distribution of vaccination policies, she noted that in 26 countries, the first dose of the \nhepatitis B vaccine is given to infants born to hepatitis B surface antigen– negative mothers at \ntwo or three months of age. She explained that this included most of Europe, listing England, \nFrance, Spain, Germany, Ireland, Norway, Denmark, Sweden, and Iceland. She pointed out that \nthe CDC had also reported variable r ates of reactogenicity within the first week of life, with data \nshowing systemic reactions among vaccinated infants. According to the data presented, up to \n5% developed a fever, 32% were drowsy or sleeping, 3% had reactions categorized as severe, \nand irrit ability, fussiness, or crying was reported for 11% within the first 24 hours and 22% within \nthe first five days. She emphasized that these were not trivial reactions and could affect up to one-third of births. She referenced the 2016 Yang study, which repo rted that hepatitis B \nvaccination impaired behavior and neurogenesis, and a 2013 study by Celich, published in the \nEuropean Journal of Pediatrics, which found that 30% of infants developed significant elevations \nin C- reactive protein without clinical signs  of sepsis and with negative blood cultures. She \nexplained that this indicated a robust inflammatory response occurring during a critical window of neurodevelopment, including neurogenesis and synaptic development. She concluded that, \ngiven these findings and CDC data on systemic adverse reactions, the committee should \nexercise caution and consider adopting a more prudent vaccination policy, similar to that of \nmost European countries, where low -risk newborns are not vaccinated on the first day of life \nand v accination is typically delayed until two to three months.  \n Dr. Malone stated that there were differences between what was presented and what was \npublished regarding the findings of the Institute of Medicine. He explained that, in his \ninterpretation, the IOM report indicated that for the 22 most claimed serious har ms, all but one \ncould not be assessed because studies had not been conducted to determine whether the \nvaccine caused harm or not. He argued that interpreting this absence of data as evidence of \nsafety was misleading. He emphasized that case reports and cas e series suggest potential \nharm, and that the IOM report did not conclude safety but rather acknowledged a lack of data. \nHe stated that for interventions in pregnancy and newborns, the burden must be to demonstrate \nsafety, not to assume safety until proven  otherwise, and he disagreed with the interpretation that \nthe absence of data implies the product is safe.  \n \nDr. Hibbeln stated that he is a strong advocate for clinical decision- making but noted that the \nwording of the question was logically inconsistent. He explained that the language said the dose \nshould not be given until one month, but also allowed for clini cal decision- making, which \n46 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  contradicts the prohibition. He suggested modifying the wording to state that the first dose of \nhepatitis B is not given until the child is one month old, except in cases where clinical decision-\nmaking dictates otherwise, which would resolve the inconsistency.  \n \nDr. Kulldorff asked whether changing the wording to “not recommended” would address the \nconcern.  \n \nDr. Hibbeln responded that the phrasing still created conflict, as it both prohibited and allowed \nadministration. He reiterated that the language should specify that the vaccine is not \nadministered until one month, except in cases where a clinical decision is made.  \n \nDr. Pollak raised a point of order, noting that the committee was debating language without a \nmotion on the floor. He reminded members of Robert’s Rules of Order, explaining that a motion \nmust be made before discussion, after which debate can occur. Then a  vote should be taken to \neither accept or reject the proposal.  \n \nDr. Malone moved to indefinitely postpone the question, noting uncertainty around safety, \neffectiveness, and timing.  \n \nDr. Pollak motioned to table, and Dr. Malone seconded.  \n Vote: To table the Hepatitis B Vaccine Vote #2  \n \n \nMotion/Vote: Hepatitis B Vaccine  \n \nDr. Pollak motioned to table the second vote on the Hepatitis B Vaccine. Dr. Malone seconded \nthe motion. No COIs were declared. The motion carried with 11 votes in favor, 1 vote opposed, \nand 0 abstentions. The disposition of the vote was as follows:  \n \n    11 Favored:  Levi, Pebsworth, Hibbeln, Pollak, Griffin, Stein, Blackburn, Milhoan, Pagano, \nMalone, Meissner  \n    1 Opposed:   Kulldorff  \n    0 Abstained:   \n \nDiscussion  \nDr. Meissner, responding to Dr. Malone’s earlier comments, stated that it is challenging to prove \nthe absence of harm and that such a goal is not practical. He emphasized that extensive \nexperience has been accumulated from administering the vaccine within the first 12 to 24 hours \nof life, and that the concerns raised about irritability or restlessness are not objective measures \nfor assessing safety. He noted that since the motion to table had passed, there would be no \nvotes on the hepatitis B vaccine during this meeting.  \n Dr. Stein cautioned against making absolute statements such as declaring the vaccine entirely \nsafe or entirely unsafe. She emphasized that the perception of safety often depends on the \nperspectives of parents and children. She advised that the committee ca refully consider the \nbroader literature and patient experiences before reaching a conclusion.  \n \nDr. Meissner responded that no vaccine is 100% safe or 100% effective. He stressed that \nproviders must weigh whether the benefits of protection outweigh possible side effects for each \n47 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  patient. He concluded that, overall, the benefits of the newborn hepatitis B vaccine clearly \noutweigh any potential adverse effects.  \n Dr. Munoz stated that she was pleased with the decision to table the vote. She emphasized that \nthere have been 30 years of progress in preventing hepatitis B disease and related cancers, \nand that the concerns raised about safety were based only on case reports and anecdotes rather than substantial evidence. She urged the committee to use proper processes to address \npotential concerns, including requesting additional studies if needed. She argued that \ndismissing a successful program would be more harmful than beneficial, given the data \npresented. She also commented on the previous vote, noting that hepatitis B testing is already a \nroutine standard of care in prenatal and obstetric practice, and she asked what the committee’s \nplan would be regarding that motion.  \n \nDr. Kulldorff responded that hepatitis B testing is currently conducted in about 86– 87% of \npregnant women, but the goal should be to move closer to 100%.  \n \nDr. Hopkins stated that if the issue of hepatitis B birth dose is revisited, it should undergo a full \nreview by a work group, including the complete evidence- to-recommendations framework, with \nparticular attention to the domains of equity and practical implementation.  \n \nDr. Goldman echoed Dr. Hopkins’ comments and asked the chair to explain what process would \nbe used in the future to review evidence. He emphasized the importance of transparency about \nwhether the committee would continue to use the evidence- to-recommendati ons framework and \nthe GRADE process that work groups have traditionally used to evaluate trial power, quality, \nbias, and conflicts of interest. He noted that recent discussions had not gone through the work \ngroup process and stated that the public should b e aware of how future evidence will be vetted. \nHe commended the committee for tabling the vote to allow further discussion but requested \nclarification on future methodology.  \n \nDr. Kulldorff stated that he hoped the committee could return to the issue at a future meeting \nand acknowledged that he could not provide a detailed response at that time.  \n Dr. Middleman stated that the concerns raised were not limited to hepatitis B but reflected \nbroader issues that had been discussed across the committee. She emphasized that no \nintervention is without risk, noting that even common treatments, such as Tylenol, amoxicillin, or \nchemotherapy drugs, carry some level of risk, as does everyday activity, such as walking across \nthe street. She explained that the committee’s scientific responsibility is to determine whether \nthe benefits outweigh the risks. She urged m embers to avoid being distracted by isolated \nstudies and to rely on systematic approaches such as the GRADE framework or the evidence -\nto-recommendations process to evaluate risks and benefits. She emphasized that the consistent \nuse of these methods is cruc ial for all vaccine decisions and that some concerns arose from \ntheir absence in recent deliberations.  \n \nDr. Levi stated that while he appreciated the emphasis on scientific methods, he was puzzled \nthat many of those advocating for rigorous approaches spoke with great confidence despite the \nabsence of gold- standard, long- term randomized clinical trials agains t a placebo. He noted that \nsuch trials do not exist for this intervention and argued that if the committee seeks to uphold scientific rigor, it should do so consistently. He cautioned that confident statements about \nvaccines being “safe and effective” were  being made without the highest standard of evidence \nand encouraged members to show greater humility and acknowledge the limitations in the \navailable data.  \n48 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  Dr. Kulldorff reminded the committee that the motion had been tabled. He encouraged those still \nwishing to comment to bring their remarks forward if the issue is returned at a future meeting. \n \nDr. Goldman stated that, as Dr. Levi had mentioned, the committee needs gold- standard \nevidence to guide decisions. He agreed that this is the role of the work groups and emphasized that the public should be adequately informed about the processes used to vet and discuss future vaccines. He emphasized that the evidence- to-recommendations framework was \nestablished to establish a consistent standard for evaluating vaccines, but noted that it had not been applied in recent deliberations. He urged the committee to clearly communicate how \nvaccine decisions will be analyzed in the future so the public can maintain trust, faith, and \nconfidence in the committee’s work.  \nDr. Kulldorff responded that Dr. Goldman had already raised this comment previously and that \nhe had addressed it at that time.  \n  \n \nPUBLIC C OMMENT  \n The floor was opened for public comment on September 18, 2025. The comments made during \nthe meeting are summarized in this document. Members of the public were also invited to \nsubmit written public comments to ACIP through the Federal eRulemaking Portal under Docket \nNumber ID CDC- 2025 -0454. Visit regulations.gov  for access to read the comments received.  \n \nMs. Anu Hosangadi  \nHepatitis B Foundation  \n \nMs. Hosangadi  spoke on behalf of the Hepatitis B Foundation, emphasizing the long-\nestablished safety and efficacy of the hepatitis B vaccine. She noted that since 1982, over a \nbillion doses have been administered worldwide with no new or unexpected safety concerns \nidentified through decades of surveillance and studies. She cited multiple CDC and Vaccine \nSafety Datalink reviews confirming the vaccine’s strong safety record, including studies in \nnewborns and infants showing no increase in adverse outcomes. She highlighted the vaccine’s \neffectiveness in providing long- term protection, its safety among pregnant women and \nindividuals with HIV, and the global data supporting continued universal birth- dose \nadministration. Ms. Hosangadi concluded by affirming that maintaining the universal hepatitis B \nbirth dose is a proven, safe, and lifesaving intervention. \n Samantha Sears,  \nNational Consumers League  \nMs. Sears, representing the National Consumers League, underscored the importance of ACIP \ngrounding its recommendations in medical science, particularly amid rising public distrust and \ndeclining vaccination rates. She urged the committee to preserve the integrity of the U.S. \nimmunization system and to combat misinformation through clear,  consistent communication. \nMs. Sears expressed concern about potential changes to the childhood vaccine schedule, \nwarning that altering established recommendations could create confusion, reduce access, and \nimpose financial burdens on families. She stressed the need for alignment between ACIP, the \nAmerican Medical Association, and the American Academy of Pediatrics to avoid contradictory \nmessaging and safeguard children’s health.  \n49 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.   \nDr. Rita Isabel Lechuga, MD, MPH  \nNASTAD  \n \nDr. Lechuga, director of the hepatitis team at NASTAD, discussed the public health benefits of \nuniversal infant hepatitis B vaccination. She traced the policy’s origins to ACIP’s 1991 recommendation, which led to a sharp decline in childhood hepatitis B cases by replacing failing \nselective vaccination strategies . She noted that universal vaccination has been both cost -\neffective and lifesaving , reducing perinatal transmission from tens of thousands of annual cases \nto fewer than 1,000  today. Dr. Lechuga desc ribed hepatitis B as one of the first “anti -cancer” \nvaccines due to its ability to prevent hepatitis D and liver cancer. She concluded by expressing hope that continued adherence to the universal birth- dose policy will lead the U.S. to eliminate \nperinatal hepatitis B transmission.  \n \nMichele Montandon  \nPrivate Citizen  \n \nMs. Montandon, a family physician and former CDC global health leader, expressed deep \nconcern about the growing spread of vaccine misinformation and its effects on public trust and \nhealth systems. Drawing from her international  experience treating vaccine -preventable \ndiseases, she condemned recent political interference in public health leadership and decision-making, including the removal of ACIP members and changes to vaccine guidance outside \nstandard scientific channels. She cited the tragic consequences of misinformation, including a recent attack on CDC headquarters, and warned that confusion among physicians and families \nis already escalating. Ms. Montandon urged the restoration of science -based leadership at HHS \nand CDC, emphasizing that delays or di sruptions to vaccination endanger public safety and \nerode confidence in the healthcare system.  \n \nDr. Judy Stone, MD  \nPrivate Citizen  \n \nDr. Stone, an infectious disease physician with over 40 years of experience, provided a powerful \naccount of witnessing children die from vaccine- preventable diseases. She reminded the \ncommittee of the tremendous progress vaccines have achieved in reducing child mortality and \ndisease incidence in the U.S. Dr. Stone warned that misinformation and vaccine hesitancy are \nreversing these gains, citing the resurgence of measles and other infections. She emphasized \nthat measles is highly contagious and can cause s evere complications, including hospitalization \nand death. Dr. Stone urged ACIP to protect access to vaccines, maintain school vaccination \nrequirements, and uphold its duty to safeguard community health, stressing that society must \nnot go back to the pre -vaccine era.  \n Mr. Scott Bertani  \nHealthHIV  \n \nMr. Bertani, director of advocacy at HealthHIV, urged the committee to uphold ACIP’s legacy as \nan independent, science -driven body. He highlighted the public health importance of the \nhepatitis B birth dose and combination vaccines such as MMRV, which protect infants and \nreduce the long- term disease burden. He noted that declining vaccine uptake threatens \nindividuals with chronic illnesses and immunocompromised populations, including people living \nwith HIV. Mr. Bertani outlined three recommendations: preser ve the evidence- based ACIP \nprocess, maintain the full immunization schedule as published, and reinstate universal COVID -\n50 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  19 vaccination for all individuals aged six months and older. He concluded by stressing that \nweakening these frameworks risks confusion, stigma, and inequities in access to care.  \n Evan Sachs \nWashington Heights– Inwood Mask Bloc  \n \nMr. Sachs, founder of the Washington Heights –Inwood Mask Bloc, spoke as a mutual aid \nprovider and journalist. He compared vaccination to traffic laws and seatbelt use, describing them as shared rules that protect both individuals and communities. He argued that public \nhealth requires collective responsibility, not personal preference, and that vaccines, while not perfect, are overwhelmingly effective and essential for community safety. Mr. Sachs also emphasized the importance of layered protections, including masking, given that no single \nintervention is 100 percent effective. He encouraged continued public health measures \ngrounded in science and social responsibility.  \n Ms. Melissa Kadri  \nPrivate Citizen  \n Ms. Kadri, a Master of Public Health student, offered an emotional testimony describing the loss \nof her uncle to COVID -19 and the subsequent death of her aunt from grief. She spoke about the \ndevastating impact on her family and the broader implications of restricted vaccine access. Ms. \nKadri emphasized the importance of maintaining herd immunity and cautioned that delaying or \nlimiting childhood vaccinations contradicts scientific evidence and endangers  lives. Using her \nfamily’s story as an example, she implored the committee not to alter vaccine schedules in ways \nthat could lead to preventable deaths and suffering, urging members to remember the human \ncost of their decisions.  \n Due to time constraints, Dr. Kulldorff announced that the discussions and votes on the MMRV \nand Hepatitis B vaccines  would continue on September 19, 2025. Summaries of those \ndiscussions and votes are included in the sections above. The meeting was then recessed until September 19, 2025, at 8:30 a.m. EST.  \n \nFRIDAY : SEPTEMBER 19, 202 5 \n \nWELCOME AND ROLL CALL  \n \nCall to Order/Roll Call  \n \nDr. Martin Kulldorff, Chair of the ACIP, convened the meeting on September  19, 2025. Dr. Mina \nZadeh, ACIP Executive Secretary from the CDC, welcomed the committee, followed by a roll call of members, ex officio members, and liaison representatives, each of whom announced \ntheir presence . \n \nAGENCY UPDATES  \n The Centers for Disease Control and Prevention (CDC)  \n Dr. Brandi Limbago, representing CDC’s National Center for Immunization and Respiratory \nDiseases (NCIRD), provided updates on response and preparedness activities. As of \n51 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  September 16, 2025, CDC confirmed 1,491 measles cases across 42 jurisdictions, the highest \nsince 1992. Of these, 86 cases were linked to 38 outbreaks, compared with 69% of cases and \n16 outbreaks in 2024. Most measles introductions originated from U.S. trav elers returning from \ncountries with active measles transmission, leading to outbreaks in under -vaccinated \ncommunities. Despite these increases, the overall risk to the general population remains low \ndue to high vaccine coverage and population immunity.  \n \nShe also reported on preparations for the 2025– 2026 respiratory virus season, focusing on \ninfluenza, COVID -19, and RSV. Current data show low flu and RSV activity but increasing \nCOVID -19 activity nationwide, with elevated emergency department visits and hospitalizations, \nparticularly among children under 5, youth 5– 17, and adults 65 and older. CDC is taking a \ncoordinated approach to address these viruses by aligning programs, data systems, outreach, and communications. Additionally, the agency continues to monitor other respiratory pathogens, \nincluding Mycoplasma, Group A Streptococcus, and Pertussis.  \n \nDr. Chris Braden provided an update on a significant outbreak response led by the National \nCenter for Emerging and Zoonotic Infectious Diseases. On September 1, CDC received reports \nfrom local sources of suspected viral hemorrhagic fever in the Kasai Provi nce of the Democratic \nRepublic of Congo, which was later confirmed as Ebola virus Zaire. The index case was a \npregnant woman admitted to Bulap General Hospital on August 20 with high fever, bloody \ndiarrhea, hemorrhaging, vomiting, and weakness; she died on  August 25 from multi -organ \nfailure. Two healthcare providers who treated her also became ill and died.  \n Genomic sequencing at the DRC’s National Public Health Laboratory indicated that the virus is \ngenetically distinct from viruses in previous Ebola outbreaks, suggesting a new spillover event \nfrom wildlife. The DRC government promptly confirmed the outbreak and collaborated with CDC to initiate an emergency response. CDC has maintained a partnership with DRC for over 20 \nyears, operating a country office since 2002 with about 30 staff members supporting laboratory \ncapacity, workforce training, and public healt h infrastructure.  \n As of September 15, there were 37 confirmed cases and 19 deaths, with additional suspected \ncases under investigation. Approximately 944 contacts have been identified, and vaccination of \nhealthcare workers and contacts began on September 13, with 369 vaccin ations completed by \nSeptember 15. All confirmed cases remain confined to Kasai Province, specifically the Bulabia \nhealth zone. The actual extent of the outbreak may be greater than currently known, though no \nrelated cases have been reported outside the DRC  or in the United States, and the overall risk \nto the U.S. public remains low.  \n \nCDC issued a Health Alert Network advisory for U.S. public health departments and clinicians \noutlining case identification, testing, and biosafety recommendations. CDC headquarters is \ncoordinating with its DRC country office, which has deployed additional staff to Kasai Province \nand Kinshasa to assist with response efforts. Technical support focuses on laboratory testing, \nsurveillance, case investigation, contact tracing, and infection prevention and control measures.  \n \nFood and Drug Administration (FDA)  \n \nDr. Tracy Beth Hoeg from the Food and Drug Administration (FDA) provided updates on recent \nregulatory actions and announcements. The four currently approved COVID -19 vaccines, \nMNEX Spike, Spikevax, Coity, and Newacovid, are indicated for adults aged 65 yea rs and older, \nas well as for individuals at increased risk for severe COVID -19. Newacovid is authorized for \nindividuals aged 12 years and older, while Spikevax is authorized for those aged six months and \n52 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  older. The previous Emergency Use Authorizations (EUAs) for Novavax, Pfizer, and Moderna \nhave been revoked.  \n For the approved vaccine formulations, there are three ongoing post-marketing commitments, \nincluding studies on the persistence of the spike protein and associated symptoms, and randomized, saline placebo- controlled trials to evaluate safety and efficacy. Dr. Hoeg \nemphasized the importance of these trials, noting that real -world evidence can sometimes be \nmisleading, citing a recent example involving the hepatitis B vaccine and apparent protection against bronchopulmonary dysplasia, which was likely due to healthy vaccine bias.  \nShe also announced that randomized controlled trials will now be required to assess the safety of administering multiple vaccines concurrently. In addition, the live attenuated ICK vaccine for \nchikungunya virus has been temporarily suspended due to safety concerns.  \n Centers for Medicare and Medicaid Services (CMS), Health Resources and Services \nAdministration (HRSA), Indian Health Service (IHS), and National Institutes of Health (NIH) did \nnot report updates.  \n \nCOVID -19 VACCINES  \n \nDr. Retsef Levi (ACIP Work Group Chair) introduced the COVID- 19 Work Group’s immediate \ngoals, which focused on discussing recently authorized vaccine products and determining which populations and subgroups should receive recommendations. Members discussed three \npossible options, which were to recommend, not recommend, or make an individual -based \ndecision, and planned to define each later in the day. The work group emphasized the need to clearly communicate all risks and uncertainties to patients, noting that the current Vaccine \nInformation Statement (VIS) does not accurately reflect the full scope of these concerns and \nshould be updated for greater clarity and consistency. Members agreed that ACIP and its work \ngroups should be able to consider any relevant data or information that supports vaccine policy decisions. Three focus clusters were established based on members’ expertise to summarize \navailable evidence, identify key issues and knowledge gaps, and develop potential policy \noptions for review by ACIP. The work group reaffirmed its commitment to using all relevant \npublished and unpublished data, including real -world experience, and to focusing on \npersonalized risk -benefit analysis rather than general statements about safety or effectiveness. \nMembers agre ed to maintain respectful debate and transparency to ensure all perspectives and \nopinions are represented.  \n Dr. Arjun Srinivasan (CDC/NCIRD) shared updates on COVID- 19 epidemiology. He explained \nthat the data presented and discussed in this section come from the COVID -19–Associated \nHospitalization Surveillance Network (COVID -NET). COVID -NET is one of three RESP -NET \nplatforms, along with RSV -NET and FluSurv -NET, that collect data using similar methods and \ncatchment areas on laboratory -confirmed COVID -19, RSV, and influenza -associated \nhospitalizations. It is a collaborative effort between CDC and state and local health departments \nthat share data through cooperative agreements.  \n COVID -NET is a collaborative, population- based surveillance system that collects data from \nmore than 300 acute care hospitals in 185 counties across 13 states, representing about 10% of \nthe U.S. population. It gathers two primary types of information: population -based hospitalization \nrates and detailed clinical data from a stratified sample of patients. These data include demographics, outcomes, underlying conditions, treatments, and discharge diagnoses.  \n \n53 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  The system’s primary purpose is to monitor laboratory -confirmed COVID -19–associated \nhospitalizations among children and adults and provide timely information to decision- makers \nand the public. Hospitalization rates are updated weekly to assess disease burden and trends, \nwhile clinical data help identify who is most at risk and evaluate illness severity. A COVID -NET \ncase is counted when a resident of the catchment area tests positive for SARS -CoV-2 within 14 \ndays before or during hospitalization. Similar def initions are used for RSV and influenza \nsurveillance systems.  \n Dr. Srinivasan noted that there has been ongoing interest in distinguishing between \nhospitalizations due to COVID -19 and those for COVID -19 illness. During the early stages of the \npandemic, when there was no immunity or vaccination and asymptomatic transmi ssion was \ncommon, hospitals screened all patients upon admission. This practice often identified patients \nwho tested positive for SARS -CoV-2 but were hospitalized for unrelated reasons, such as \nsurgery or childbirth. To address this, COVID -NET implemented an algorithm to identify \nhospitalizations primarily due to COVID -19, based on chief complaint and history of present \nillness. Data using this approach, dating back to March 2020, are posted monthly on the public \nCOVID -NET dashboard. Although routine univer sal screening of all hospital admissions has \nlargely ended, COVID -NET continues to use this algorithm to maintain consistency in \nsurveillance.  \n \nSeveral factors must be considered when defining hospitalizations due to COVID -19. A positive \nSARS- CoV-2 test can influence the decision to admit a patient with comorbidities or other \nunderlying conditions. At the same time, the presence of comorbidities o r other conditions can \nalso affect the decision to accept a SARS -CoV-2–positive patient. Data obtained from medical \nrecords, such as test results, treatments, discharge diagnoses, and coding, may lead to \nmisclassification of hospitalizations as COVID -19-related or unrelated. ICD -10-CM codes in the \nU.S. are designed for billing and administrative purposes, not surveillance, and may either overcount or undercount true cases. In some instances, a COVID -19 ICD code can be used \nonly to indicate a positive test r ather than hospitalization for COVID -19 illness.  \n COVID -NET uses a standardized process to determine whether hospitalizations are due to \nCOVID -19. This process relies on information from the chief complaint and history of present \nillness recorded at admission. Hospitalizations are classified as non- COVID -19-related if the \nadmission was for obstetric care, surgery, psychiatric reasons, trauma, or for newborns \nhospitalized at birth. For remaining cases, if the medical record documents fever, respiratory \nsymptoms, a COVID -19–like illness, or suspicion for COV ID-19, the hospitalization is classified \nas due to COVID -19. Cases that do not clearly fit these criteria are reviewed by two COVID -\nNET physicians, with a third review if needed. Suppose a patient’s medical record indicates that \na positive SARS -CoV-2 test was incidental or that the hospitalization occurred for an unrelated \nreason, such as a localized infection or a surgical procedure. In that case, the case is classified \nas not related to COVID -19. \n Using this algorithm, 87% of hospitalizations among SARS -CoV-2–positive patients in COVID -\nNET were determined to be due to COVID -19. Rates have increased over time, likely because \nuniversal screening of asymptomatic patients is no longer standard. Among children, 89% of hospitalizations were due to COVID -19, and the percentage increased with age in adults. Adults \naged 65 years and older accounted for 70% of COVID -19–associated hospitalizations, with 91% \nof those admissions determined to be primarily due to COVID -19. \n \nCOVID -NET balances the need for detailed clinical data with the workload of chart abstraction. \nData collection can be limited by timing and access, since ICD -10 codes are assigned after \n54 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  discharge and may only be available in billing systems. To address this, surveillance officers \nalso review discharge summaries to capture conditions that developed during hospitalization. \nCombining discharge summaries with ICD -10 codes provides a more complete picture of each \ncase and reduces bias that can occur when relying solely on billing data for public health \nsurveillance.  \n \nCOVID -NET examined classif ying hospitalizations as being due to COVID -19using two different \napproaches: ICD -10-CM discharge diagnoses and the network’s reason- for-admission \nalgorithm. Data from the 2023– 2024 season were used since ICD -10-CM codes are not yet \navailable for the 2024– 2025 season. During this period, COVID -NET identified more than \n66,000 hospitalizations among patients of all ages, of which 7,279 were sampled for medical record abstraction. Using ICD -10-CM codes and discharge diagnoses, 81% of sampled \nhospitalizations had a COVID -19 discharge code listed in one of the first nine coding positions, \n52% had a sepsis or respiratory -related diagnosis, and 88% had either a COVID -19 ICD -10 \ncode or a respiratory diagnosis. 12% of cases had neither  a COVID -19 ICD -10-CM code nor \nsepsis or respiratory -related discharge diagnosis . \n Applying the reason- for-admission algorithm to the same sample, 85% of hospitalizations were \nclassified as due to COVID -19. Of these, 91% also had either a COVID -19 ICD -10 code or a \nsepsis or respiratory -related diagnosis. Among the remaining 15% classified as hospitalizations \nwith COVID -19, 64% had a COVID -19 ICD -10 diagnosis code.  \n \nDr. Srinivasan summarized that the two classification methods show strong agreement. Overall, 88% of hospitalizations had a COVID -19 ICD -10 code or a respiratory -related diagnosis, and \n85% were identified as COVID -19 as the likely primary reason for admiss ion. 92% of \nhospitalizations identified through the reason- for-admission approach also had a COVID -19 \nICD-10 code or a sepsis or respiratory diagnosis. The reason -for-admission approach is more \nconservative than relying solely on discharge diagnoses and can be completed more quickly. \nThese findings support the notion that COVID -NET’s methods provide a balanced approach to \ntimeliness, accuracy, and population representation.  \n \nCOVID -19–associated hospitalization rates per 100,000 population were determined by age \ngroup and reflect the cumulative risk of hospitalization for the 12 months from October 2024 \nthrough September 2025. The rates were based on the surveillance standard, which includes \nhospitalized residents in the COVID -NET catchment area who tested positive for SARS -CoV-2. \nHospitalization rates were highest among adults aged 65 to 74 years and 75 years and older, as well as among infants younger than 6 months. Because no vaccine products are approved for \ninfants under 6 months of age, protection against hospitalization must come from maternal \nvaccination.  \n \nA significant proportion of adults hospitalized due to COVID -19 experienced severe in- hospital \noutcomes, including admission to the intensive care unit and in- hospital death. About 15% of \nadults hospitalized with COVID -19 were admitted to the ICU, and in -hospital death occurred \nmore frequently among adults aged 50 years and older. Among all adults hospitalized due to \nCOVID -19 who died in the hospital, 84% were aged 50 years and older. These data include only \ndeaths that occurred during hospitalization, although additional COVID -19–associated deaths \noccur outside the hospital, including some within 30 days after discharge.  \n \nDifferent respiratory viruses affect age groups differently, with the greatest overall impact seen \nat the extremes of age. Cumulative data show that RSV causes the highest burden of \nrespiratory disease in children under one year. COVID -19 has the greatest impact on older \n55 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  adults but also remains a significant cause of hospitalization among infants, with rates \ncomparable to influenza during October 2024 -2025, a high- severity influenza season  that was \nthe most severe since the 2010– 2011 season. COVID -19–associated hospitalization rates \namong infants younger than 6 months have remained close to those among adults aged 65 to \n74 years, but in recent weeks have risen more rapidly, reaching 223 per 100,000 c ompared to \n194 per 100,000 among adults, a 14% higher rate among infants  compared to adults aged 65 to \n74. \n \nDr. Srinivasan shared an update to a peer -reviewed study published in 2021, which had \ninformed a previous infographic summarizing the relative risk of hospitalization among individuals with chronic conditions compared to those without. Data sources for the updated \nanalysis included three primary datasets: COVID -NET data on hospitalizations due to COVID -\n19 from October 2022 through September 2023; the Behavioral Risk Factor Surveillance System (BRFSS), the largest ongoing health survey system in the world th at collected data \nannually from hundreds of thousands of community -dwelling U.S. adults; and population data \nfrom the U.S. Census provided by the National Center for Health Statistics.  \n \nThe analysis methodology was complex. COVID -NET provided weighted counts of individuals \nhospitalized due to COVID -19 who had underlying conditions, limited to community -dwelling \nadults aged 18 years and older, for consistency with BRFSS data. Weighted coun ts of adults \nwith and without chronic diseases of interest were calculated using BRFSS data and state \npopulation modeling. Adjusted rate ratios of hospitalization rates for adults with versus without \nchronic conditions were then calculated. Chronic conditi ons examined were limited to those \nincluded in the BRFSS survey  and included coronary artery disease, history of stroke, diabetes \nmellitus, chronic kidney disease, COPD, asthma, obesity, severe obesity, and current smoker . \n \nFindings showed that the prevalence of most chronic conditions among adults hospitalized due \nto COVID -19 was higher than in the general population. Among adults, most chronic conditions \nincreased the risk of being hospitalized due to COVID -19. The risk for hospitalization conferred \nby several conditions, such as coronary artery disease, diabetes, and obesity, appeared to \ndecline with age but this may have reflected challenges in adjusting for coexisting conditions or \nlow prevalence of some diseases within s pecific age groups; for example, severe obesity was \nuncommon among adults aged 75 years and older, while COPD was uncommon among adults \nyounger than 50 years.  \n The analysis also showed that the risk for hospitalization due to COVID -19 increased with both \nthe number of chronic conditions and with age. Having multiple comorbid conditions and older age were the strongest risk factors for hospitalization due to COVID -19 identified among adults . \nAdults with three or more underlying conditions were nearly six times more likely to be \nhospitalized due to COVID -19 compared with those with no underlying conditions. \nHospitalization rates were 18.5 times higher among adults aged 75 years and older compared with those aged 18 to 49 years, making age 75 and above the greatest identified risk factor for \nhospitalization.  \n \nThe analysis had several strengths, including the use of data from a robust COVID -19 \nhospitalization surveillance system that enabled comparisons across state -level prevalence data \nand allowed examination of how specific conditions, multiple comorbidities,  and age contributed \nto hospitalization risk. However, there were also limitations. The results remained preliminary \nand under review. The analysis was limited to community -dwelling adults and did not include \nchildren or individuals living in long- term car e facilities, where risks may have differed. Some \nconditions tended to co -occur, such as diabetes and chronic kidney disease, and adjustments \n56 \nNote: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  for these comorbidities could not always be made due to limited data, particularly in younger \nadults. In addition, differences in rate ratios by outcomes (e.g., ICU admission) or by race and \nethnicity could not be assessed due to the sparse data.  \n \nDr. Malone asked whether there was a significant overlap and diagnostic difficulty between \nCOVID -19 and other influenza- like illnesses.  \n \nDr. Srinivasan confirmed that the symptoms of COVID -19 overlapped almost entirely with those \nof other respiratory illnesses.  \n \nDr. Malone noted that when he had previously asked a CDC representative about the specificity \nand sensitivity of the diagnostic tests used, he was told those measures were “academic.” He \nexpressed concern that sensitivity and specificity are fundamental to  data validity and stated \nthat diagnostic testing for COVID -19 has had limitations in both areas, which were not reflected \nin the models.  \n \nThe NCIRD SME explained that the tests used in COVID -NET were FDA -approved diagnostic \ntests performed in hospitals and medical clinics nationwide. The SME clarified that COVID -NET \ndid not conduct testing directly and that all tests were performed at the tr eating provider's \ndiscretion.  \n \nDr. Malone stated that this confirmed the tests had known limitations in sensitivity and specificity \nthat could affect data interpretation.  \n \nThe NCIRD SME acknowledged that all clinical tests have defined sensitivity and specificity \nvalues but emphasized that the tests used were FDA -approved and used to identify patients \nwho tested positive for SARS -CoV-2. \n \nDr. Malone added that if the tests were only 80% specific, the underlying classification of \nCOVID -19 cases would be similarly ambiguous.  \n \nDr. Natalie Thornburg, NCIRD laboratory SME, clarified that all tests used in COVID -NET had \nre\n…[truncated]", "summary": "MEETING OF THE ADVISORY  COMMITTEE ON IMMUNIZATION  PRACTICES (ACIP)     SEPTEMBER  18-19, 2025   MEETING SUMMARY                                                                            Trade names are used for identification purposes only and do not indicate endorsement.           2  Note: Text enclosed in [brackets] was added following the meeting, per the presenter’s request.  THURSDAY : SEPTEMBER 18, 202 5    WELCOME AND ROLL CALL     Call to Order/Roll Call     Dr. Mina Zadeh, ACIP…", "source_url": "https://www.cdc.gov/acip/meetings/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/minutes/summary-2025-9-18-19-508.pdf", "doc_date": "2025-09-18", "case": "acip", "sub_case": "minutes", "tags": ["acip", "cdc", "vaccines", "minutes"], "page_count": 104}
{"title": "Final posted 2025 06 24 508", "content": "Final Agenda\n10:00 Opening Remarks Dr. Martin Kulldorff (ACIP Chair)\n10:15 Welcome and Roll Call Dr. Mina Zadeh (ACIP Executive Secretary, CDC)\n10:35 Update on Work Groups Dr. Martin Kulldorff (ACIP Chair)\n11:00 COVID-19 Vaccines\nIntroduction Dr. Adam MacNeil (CDC/NCIRD)\nCOVID-19 epidemiology Dr. Adam MacNeil (CDC/NCIRD)\nCOVID-19 vaccine effectiveness update Dr. Adam MacNeil (CDC/NCIRD)\nCOVID-19 safety update Dr. Sarah Meyer (CDC/NCEZID)\nCOVID-19 vaccine coverage and implementation Dr. Georgina Peacock (CDC/NCIRD)\nEvidence to recommendations (partial) Dr. Adam MacNeil (CDC/NCIRD)\n1:00 Lunch\n1:30 Agency Updates CDC, CMS, FDA, HRSA, IHS, NIH\n2:00 RSV Vaccines- Maternal/Pediatric\nIntroduction Dr. Adam MacNeil (CDC/NCIRD)\nUpdates on uptake of maternal vaccine and nirsevimab  Dr. Georgina Peacock (CDC/NCIRD)\nEffectiveness and impact of RSV prevention products in infants \nduring the 2024-2025 seasonDr. Adam MacNeil (CDC/NCIRD)\nUpdates on safety of maternal vaccine and nirsevimab Dr. Malini DeSilva (HealthPartners),\nDr. Matthew Daley (Kaiser Permanente Colorado)\nUpdates and summary of the Evidence to Recommendation \nFramework for clesrovimabDr. Adam MacNeil (CDC/NCIRD)\nUpdates on clinical considerations for clesrovimab Dr. Adam MacNeil (CDC/NCIRD)\nProposed Recommendations Dr. Adam MacNeil (CDC/NCIRD)\nUpdates to RSV vaccines VFC resolution Dr. Georgina Peacock (CDC/NCIRD)\n4:00 Break\n4:15 Public Comment\n5:00 Votes\nRSV Vaccines- Pediatric Dr. Adam MacNeil (CDC/NCIRD)\nRSV Vaccines- VFC Dr. Georgina Peacock (CDC/NCIRD)\n5:30 AdjournMEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)\nCenters for Disease Control and Prevention\nAtlanta, Georgia 30329  \nWednesday, June 25, 2025\nFinal Agenda\n8:00 Welcome and Roll Call Dr. Mina Zadeh (ACIP Executive Secretary, CDC)\n8:15 Influenza Vaccines\nIntroduction Dr. Vivien Dugan (CDC/NCIRD)\nFlublok in older children and adolescents: immunogenicity and safety Dr. Pedro Folegatti (Sanofi Pasteur)\nEstimates of influenza burden and burden averted through vaccination Dr. Vivien Dugan (CDC/NCIRD)\nProposed recommendations for 2025-26\nPresentation regarding thimerosal in vaccines\nProposed recommendations regarding thimerosal containing influenza \nvaccine\n10:15 Break\n10:30 Chikungunya Vaccines\nIntroduction\nEtR (partial) for use of live attenuated and virus-like particle \nchikungunya \nvaccines in U.S territories\nSafety update on live attenuated chikungunya vaccine and use among \nolder persons\n10:45 Anthrax Vaccine\n10:50 MMRV Vaccine\nPresentation on MMRV vaccine in children under under 4 years of \nage\nProposed recommendations regarding MMRV in children under 4 \nyears of age\n11:20 Break\n11:30 Public Comment\n12:15 Break\n12:30 Votes\nInfluenza Vaccines\nThimerosal containing influenza vaccine recommendationsDr. Vivien Dugan (CDC/NCIRD) \nLyn Redwood, RN, MSN \nDr. Martin Kulldorff (ACIP Chair) \nDr. Lyle Petersen (CDC/NCEZID)  \nDr. Lyle Petersen (CDC/NCEZID)\nDr. Lyle Petersen (CDC/NCEZID) \nDr. Brendan Jackson (CDC/NCEZID) \nDr.\n Martin Kulldorff (ACIP Chair)       \nDr. Martin K\nulldorff  (ACIP Chair)\nDr. Vivien Dugan\n \nDr. Martin Kulldorff  (ACIP  Chair)\n1:00 Adjourn\nAcronyms\nCDC Centers for Disease Control and Prevention\nCMS Centers for Medicare & Medicaid Services\nCOVID-19 Coronavirus disease 2019\nEtR Evidence to Recommendations Framework\nFDA Food and Drug Administration\nHRSA Health Resources and Services Administration\nIHS Indian Health Service\nMMRV Measles, Mumps, Rubella, Varicella Vaccine\nNCIRD National Center for Immunization & Respiratory Diseases\nNCEZID National Center for Emerging and Zoonotic Diseases \nNIH National Institutes of Health\nRSV Respiratory Syncytial Virus \nVFC Vaccines for ChildrenThursday, June 26, 2025", "summary": "Final Agenda 10:00 Opening Remarks Dr. Martin Kulldorff (ACIP Chair) 10:15 Welcome and Roll Call Dr. Mina Zadeh (ACIP Executive Secretary, CDC) 10:35 Update on Work Groups Dr. Martin Kulldorff (ACIP Chair) 11:00 COVID-19 Vaccines Introduction Dr. Adam MacNeil (CDC/NCIRD) COVID-19 epidemiology Dr. Adam MacNeil (CDC/NCIRD) COVID-19 vaccine effectiveness update Dr. Adam MacNeil (CDC/NCIRD) COVID-19 safety update Dr. Sarah Meyer (CDC/NCEZID) COVID-19 vaccine coverage and implementation Dr.…", "source_url": "https://www.cdc.gov/acip/meetings/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/agendas/Final-posted-2025-06-24-508.pdf", "doc_date": "2025-06-24", "case": "acip", "sub_case": "agendas", "tags": ["acip", "cdc", "vaccines", "agendas"], "page_count": 2}
{"title": "draft posted 2025 06 23", "content": "Draft Agenda\n10:00 Welcome and Roll Call Dr. Mina Zadeh (ACIP Executive Secretary, CDC)\n10:20 Update on Work Groups TBD\n11:00 COVID-19 Vaccines\nIntroduction TBD\nCOVID-19 epidemiology Dr. Adam MacNeil (CDC/NCIRD)\nCOVID-19 vaccine effectiveness update Dr. Adam MacNeil (CDC/NCIRD)\nCOVID-19 safety update Dr. Sarah Meyer (CDC/NCEZID)\nCOVID-19 vaccine coverage and implementation Dr. Georgina Peacock (CDC/NCIRD)\nEvidence to recommendations (partial) Dr. Adam MacNeil (CDC/NCIRD)\n1:00 Lunch\n1:30 Agency Updates CDC, CMS, FDA, HRSA, IHS, NIH\n2:00 RSV Vaccines- Maternal/Pediatric\nIntroduction TBD\nUpdates on uptake of maternal vaccine and nirsevimab  Dr. Georgina Peacock (CDC/NCIRD)\nUpdates on the impact and epidemiology of maternal vaccine and \nnirsevimabDr. Adam MacNeil (CDC/NCIRD)\nUpdates on the effectiveness of maternal vaccine and nirsevimab Dr. Adam MacNeil (CDC/NCIRD)\nUpdates on safety of maternal vaccine and nirsevimab Dr. Malini DeSilva (HealthPartners),                                  \nDr. Matthew Daley (Kaiser Permanente Colorado)\nUpdates and summary of the Evidence to Recommendation \nFramework for clesrovimabDr. Adam MacNeil (CDC/NCIRD)\nUpdates on clinical considerations for clesrovimab Dr. Adam MacNeil (CDC/NCIRD)\nProposed Recommendations Dr. Adam MacNeil (CDC/NCIRD)\nUpdates to RSV vaccines VFC resolution Dr. Georgina Peacock (CDC/NCIRD)\n4:00 Break\n4:15 Public Comment\n5:00 Votes\nRSV Vaccines- Maternal/Pediatric Dr. Adam MacNeil (CDC/NCIRD)\nRSV Vaccines- VFC Dr. Georgina Peacock (CDC/NCIRD)\n5:30 AdjournMEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)\nCenters for Disease Control and Prevention\nAtlanta, Georgia 30329  \nWednesday, June 25, 2025\nDraft Agenda\n8:00 Welcome and Roll Call Dr. Mina Zadeh (ACIP Executive Secretary, CDC)\n8:15 Influenza Vaccines\nIntroduction TBD\nFlublok in older children and adolescents: immunogenicity and safety Dr. Pedro Folegatti (Sanofi Pasteur)\nEstimates of influenza burden and burden averted through vaccination Dr. Vivien Dugan (CDC/NCIRD)\nProposed recommendations for 2025-26 Dr. Vivien Dugan (CDC/NCIRD)\nPresentation regarding thimerosal in vaccines TBD\nProposed recommendations regarding thimerosal containing influenza \nvaccineTBD\n10:15 Break\n10:30 Chikungunya Vaccines\nIntroduction\nEtR (partial) for use of live attenuated and virus-like particle \nchikungunya \nvaccines in U.S territories\nSafety update on live attenuated chikungunya vaccine and use among \nolder persons\n10:45 Anthrax Vaccine\n10:50 MMRV Vaccine\nPresentation on MMRV vaccine in children under under 4 years \nof age\nProposed  recommendations regarding MMRV in children under \n4 years of age\n11:20 Break\n11:30 Public Comment\n12:15 Break\n12:30 Votes\nInfluenza Vaccines\nThimerosal containing influenza vaccine recommendationsTBD\nDr. Lyle Petersen (CDC/NCEZID)\nDr. Lyle Petersen (CDC/NCEZID)\nDr. Brendan Jackson (CDC/NCEZID)  \nT\nBD\nTBD\nDr. Vi v ien Du g an (C DC/NCIRD) \nTBD\n1:00 Adjourn\nAcronyms\nCDC Centers for Disease Control and Prevention\nCMS Centers for Medicare & Medicaid Services\nCOVID-19 Coronavirus disease 2019\nEtR Evidence to Recommendations Framework\nFDA Food and Drug Administration\nHRSA Health Resources and Services Administration\nIHS Indian Health Service\nMMRV Measles, Mumps, Rubella, Varicella Vaccine\nNCIRD National Center for Immunization & Respiratory Diseases\nNCEZID National Center for Emerging and Zoonotic Diseases \nNIH National Institutes of Health\nRSV Respiratory Syncytial Virus \nVFC Vaccines for ChildrenThursday, June 26, 2025", "summary": "Draft Agenda 10:00 Welcome and Roll Call Dr. Mina Zadeh (ACIP Executive Secretary, CDC) 10:20 Update on Work Groups TBD 11:00 COVID-19 Vaccines Introduction TBD COVID-19 epidemiology Dr. Adam MacNeil (CDC/NCIRD) COVID-19 vaccine effectiveness update Dr. Adam MacNeil (CDC/NCIRD) COVID-19 safety update Dr. Sarah Meyer (CDC/NCEZID) COVID-19 vaccine coverage and implementation Dr. Georgina Peacock (CDC/NCIRD) Evidence to recommendations (partial) Dr. Adam MacNeil (CDC/NCIRD) 1:00 Lunch 1:30 Agency…", "source_url": "https://www.cdc.gov/acip/meetings/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/agendas/draft-posted-2025-06-23.pdf", "doc_date": "2025-06-23", "case": "acip", "sub_case": "agendas", "tags": ["acip", "cdc", "vaccines", "agendas"], "page_count": 2}
{"title": "draft posted 2025 06 18", "content": "Draft Agenda\n10:00 Welcome and Roll Call Dr. Mina Zadeh (ACIP Executive Secretary, CDC)\n10:20 Update on Work Groups TBD\n11:00 COVID-19 Vaccines\nIntroduction TBD\nCOVID-19 epidemiology Dr. Adam MacNeil (CDC/NCIRD)\nCOVID-19 vaccine effectiveness update Dr. Adam MacNeil (CDC/NCIRD)\nCOVID-19 safety update TBD\nCOVID-19 vaccine coverage and implementation Dr. Georgina Peacock (CDC/NCIRD)\nEvidence to recommendations (partial) Dr. Adam MacNeil (CDC/NCIRD)\n1:00 Lunch\n1:30 Agency Updates CDC, CMS, FDA, HRSA, IHS, NIH\n2:00 RSV Vaccines- Maternal/Pediatric\nIntroduction TBD\nUpdates on uptake of maternal vaccine and nirsevimab  Dr. Georgina Peacock (CDC/NCIRD)\nUpdates on the impact and epidemiology of maternal vaccine and \nnirsevimabDr. Adam MacNeil (CDC/NCIRD)\nUpdates on the effectiveness of maternal vaccine and nirsevimab Dr. Adam MacNeil (CDC/NCIRD)\nUpdates on safety of maternal vaccine and nirsevimab TBD\nUpdates and summary of the Evidence to Recommendation \nFramework for clesrovimabDr. Adam MacNeil (CDC/NCIRD)\nUpdates on clinical considerations for clesrovimab Dr. Adam MacNeil (CDC/NCIRD)\nProposed Recommendations Dr. Adam MacNeil (CDC/NCIRD)\nUpdates to RSV vaccines VFC resolution Dr. Georgina Peacock (CDC/NCIRD)\n4:00 Break\n4:15 Public Comment\n5:00 Votes\nRSV Vaccines- Maternal/Pediatric Dr. Adam MacNeil (CDC/NCIRD)\nRSV Vaccines- VFC Dr. Georgina Peacock (CDC/NCIRD)\n5:30 AdjournMEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)\nCenters for Disease Control and Prevention\nAtlanta, Georgia 30329  \nWednesday, June 25, 2025\nDraft Agenda\n8:00 Welcome and Roll Call Dr. Mina Zadeh (ACIP Executive Secretary, CDC)\n8:15 Influenza Vaccines\nIntroduction TBD\nFlublok in older children and adolescents: immunogenicity and safety Dr. Pedro Folegatti (Sanofi Pasteur)\nEstimates of influenza burden and burden averted through vaccination Dr. Vivien Dugan (CDC/NCIRD)\nProposed recommendations for 2025-26 Dr. Vivien Dugan (CDC/NCIRD)\nPresentation regarding thimerosal in vaccines TBD\nProposed recommendations regarding thimerosal containing influenza \nvaccineTBD\n10:15 Break\n10:30 Chikungunya Vaccines\nIntroduction TBD\nEtR (partial) for use of live attenuated and virus-like particle \nchikungunya \nvaccines in U.S territoriesDr. Lyle Peterson (CDC/NCEZID)\nSafety update on live attenuated chikungunya vaccine and use among \nolder personsDr. Lyle Peterson (CDC/NCEZID)\n10:45 Anthrax Vaccine Dr. Brenden Jackson (CDC/NCEZID)\n10:50 MMRV Vaccine\nTBD Presentation on MMRV vaccine in children under under 4 years \nof age\nProposed recommendations regarding MMRV in children under \n4 years of ageTBD\n11:20 Break\n11:30 Public Comment\n12:15 Break\n12:30 Votes\nInfluenza Vaccines Dr. Vivien Dugan (CDC/NCIRD)\nThimerosal containing influenza vaccine recommendations TBD\n1:00 Adjourn\nAcronyms\nCDC Centers for Disease Control and Prevention\nCMS Centers for Medicare & Medicaid Services\nCOVID-19 Coronavirus disease 2019\nEtR Evidence to Recommendations Framework\nFDA Food and Drug Administration\nHRSA Health Resources and Services Administration\nIHS Indian Health Service\nMMRV Measles, Mumps, Rubella, Varicella Vaccine\nNCIRD National Center for Immunization & Respiratory Diseases\nNCEZID National Center for Emerging and Zoonotic Diseases \nNIH National Institutes of Health\nRSV Respiratory Syncytial Virus \nVFC Vaccines for ChildrenThursday, June 26, 2025", "summary": "Draft Agenda 10:00 Welcome and Roll Call Dr. Mina Zadeh (ACIP Executive Secretary, CDC) 10:20 Update on Work Groups TBD 11:00 COVID-19 Vaccines Introduction TBD COVID-19 epidemiology Dr. Adam MacNeil (CDC/NCIRD) COVID-19 vaccine effectiveness update Dr. Adam MacNeil (CDC/NCIRD) COVID-19 safety update TBD COVID-19 vaccine coverage and implementation Dr. Georgina Peacock (CDC/NCIRD) Evidence to recommendations (partial) Dr. Adam MacNeil (CDC/NCIRD) 1:00 Lunch 1:30 Agency Updates CDC, CMS, FDA,…", "source_url": "https://www.cdc.gov/acip/meetings/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/agendas/draft-posted-2025-06-18.pdf", "doc_date": "2025-06-18", "case": "acip", "sub_case": "agendas", "tags": ["acip", "cdc", "vaccines", "agendas"], "page_count": 2}
{"title": "summary 2025 06 25 26 508", "content": "MEETING OF THE ADVISORY \nCOMMITTEE ON IMMUNIZATION \nPRACTICES (ACIP)  \n \nJ\nUNE 25-26 , 2025 \nMEETING SUMMARY  \n \n \n \n \n \n  \n \n \n \n \n  \n \n \n \n \n \n  \n \n \n \n \n \n \n \n \n  \n \n \n \n  \n \n \nTr\nade names are used for identification purposes only and do not indicate endorsement.  \n  \n \n \n2 \n WEDNESDAY : JUNE  25, 2025 \n \nWELCOME AND I NTRODUCTIONS  \n \nC\nall to Order/Roll Call  \n \nD\nr. Martin Kulldorff, Chair of the ACIP, convened the meeting on June 25, 2025. He welcomed \nthe members, thanked the current and former committee members and CDC staff, and \nemphasized the committee’s commitment to evidence- based vaccine recommendations. Dr. \nKulldorff stressed the importance of open scientific inquiry, rebuilding public trust, and addressing vaccine safety transparently to support public health.  \n \nD\nr. Mina Zadeh (ACIP Executive Secretary, CDC) made opening announcements about the \navailability of presentation slides on the ACIP website, the scheduled oral public session, and \nthe written public comment process. She reviewed conflict of interest polici es for ACIP \nmembers. A list of Members, Ex Officios, and Liaison Representatives is included in the appendices at the end of this summary document. She welcomed the new committee members \nwho introduced themselves:  Dr. Martin Kulldorff, Dr. Joseph Hibbeln,  Dr. Retsef Levi, Dr. \nRobert Malone, Dr. Cody Meissner, Dr. James Pagano, and Dr. Vicky Pebsworth. While no \nconflicts of interest were identified for the first day of the meeting, Dr. Vicky Pebsworth disclosed \nthat she owns stock in a healthcare sector fund that includes holdings relevant to ACIP \ndiscussions, including vaccine manufacturers. However, the value of this stock falls below the \nOffice of Government Ethics’ de minimis threshold. Dr. Pebsworth confirmed that she understood, and therefore, she is permitted to participate fully in the ACIP meeting.  \n \nUPDATE ON WORK GROUPS  \n \nD\nr. Kulldorff emphasized the critical role of ACIP work groups, which are composed of national \nexperts who investigate vaccine- related issues and provide recommendations to the committee. \nNew chairs are being appointed to lead these groups, while many current members will continue their work to ensure continuity and progress. There are currently 11 active work groups focusing \non vaccines for chikungunya, COVID- 19, cytomegalovirus, HPV, influenza, meningococcal \ndisease, pneumococcal disease, and RSV. Dr. Kulldorff announced plans to establish new work \ngroups, including one to evaluate the cumulative childhood and adolescent vaccine schedules. \nThis group will assess potential interactions between vaccines, the total number of vaccines \nadministered, ingredient amounts, and the timing of administration. The National Academy of \nMedicine has previously called for additional research in this area. Another new work group will \nreview vaccines that have not been formally reassessed in over seven years, a practice intended to be routine but not yet systematically implemented. Future topics for review may \ninclude the timing of the hepatitis B birth dose, whether separate MMR and varicella vaccines \nshould be preferred over the combined MMRV due to seizure risks, and the possibility of \nconsidering alternative MMR vaccines used in other countries. Dr. Kulldorff emphasized the \nimportance of collaboration, open scientific discussion, and a commitment to evidence -based \nmedicine in enhancing public health outcomes.  \n  \n \n \n \n3 \n COVID -19 VACCINES  \n \nD\nr. Adam MacNeil (CDC/NCIRD) provided a recap to summarize events of the past year. Last \nJune, ACIP recommended the 2024– 2025 COVID -19 vaccination for all individuals aged 6 \nmonths and older. In August, the FDA authorized or approved Moderna, Pfizer, and N ovavax \nCOVID -19 vaccines, and in September, ACIP’s recommendations and CDC vaccination \nguidance were published in the Morbidity and Mortality Weekly Report (MMWR).  \nAt the October 2024 ACIP meeting, the committee recommended additional doses for adults \naged 65 and older and for individuals aged 6 months and older with moderate or severe \nimmunocompromise. These recommendations were published in the MMWR in December \n2024. As has been customary following changes in recommendations, CDC updated its interim clinical considerations accordingly. \nThe CDC updated its recommendations in May 2025. Per HHS directive, guidance shifted to \nshared clinical decision- making for healthy children aged 6 months through 17 years, and no \nrecommendation was provided for pregnant individuals. Also in May, the FDA approved Novavax’s NUVAXOVID (2024–2025 Formula) and Moderna’s MNEXSPIKE (2024– 2025 \nFormula) for individuals aged 12– 64 at high risk for severe COVID -19, and for all individuals \naged 65 and older.  \nOn May 22, 2025, FDA’s Vaccines and Related Biological Products Advisory Committee \n(VRBPAC) met to discuss strain selection for the 2025– 2026 COVID -19 vaccine formula. FDA \nsubsequently advised manufacturers to use a monovalent JN.1 -lineage- based antigen \ncomposition, preferably the LP.8.1 strain.  \nDr. MacNeil provided an overview of the current routine COVID -19 vaccine schedule by age \ngroup. Children aged 6 months to 4 years who are unvaccinated may receive a multidose initial series with a 2024–2025 COVID -19 mRNA vaccine, using shared clinical decision -making. \nThose who have previously completed an initial series may receive one dose of a 2024– 2025 \nmRNA vaccine from the same manufacturer, under shared clinical decision- making.  \nIndividuals aged 5– 17 years may receive one age -appropriate dose of a 2024– 2025 COVID -19 \nvaccine using shared clinical decision- making. Adults aged 18–64 years should receive one \ndose of any 2024– 2025 COVID -19 vaccine, while those aged 65 and older should receive two \ndoses of any 2024– 2025 COVID -19 vaccine, spaced six months apart.  \nThe current recommendations for individuals with moderate or severe immunocompromise were \nalso reviewed. Those who are unvaccinated should receive a multidose vaccination series with an age- appropriate 2024 –2025 COVID -19 vaccine, followed by one additional  2024–2025 \nvaccine dose six months after completing the initial series. \nIndividuals who have previously completed an initial series should receive two doses of an age-\nappropriate 2024– 2025 COVID -19 vaccine, spaced six months apart. Additional age-\nappropriate 2024– 2025 COVID -19 vaccine doses may be administered under shared clinical \ndecision- making.  \nIt was noted that COVID -19 vaccines have had interim recommendations since 2020, \ndeveloped with the understanding they would be revisited as new information became available.  \nIn recent years, the work group explored non- universal recommendations, which would apply \nonly to specific age or risk groups. At the ACIP meetings in September 2023 and June 2024, the work group presented interpretation summaries outlining discussions on universal versus non -\nuniversal policy options for the 2023– 2024 and 2024– 2025 vaccines, respectively.  \n4 \n Based on the available evidence and implementation considerations, a universal \nrecommendation was ultimately supported. Since November 2024, the work group has \ndiscussed recommendations for the 2025– 2026 season. At the April 2025 ACIP meeting, \nmembers cons idered adopting a non -universal recommendation.  \nDr. MacNeil summarized that between November 2024 and June 2025, the COVID -19 work \ngroup reviewed epidemiology and disease burden, vaccine effectiveness, safety, and \nimplementation considerations. At the most recent work group meeting on June 5 and follow -up \npolling, the group agreed on recommendation categories for the 2025– 2026 COVID -19 \nvaccines. These include age- appropriate vaccination for all infants and children aged 6– 23 \nmonths, as well as for individuals aged 2– 64 years who are at high risk for severe COVID -19 \n(including pregnant individuals), those at high risk of exposure, and those who desire additional protection under shared clinical decision- making. The group also supported a recommendation \nfor two doses of the 2025– 2026 COVID -19 vaccine for adults aged 65 and older, as well as for \nindividuals aged 6 months and older with moderate or severe immunocompromise.  \nDr. Adam MacNeil (CDC/NCIRD) provided an update on the current epidemiology of COVID -19. \nCDC estimates that since October 1, 2024, there have been between 9.8 and 16.1 million \nCOVID -19–associated illnesses, 2.4 to 3.8 million outpatient visits, 270,000 to 440,000 \nhospitalizations, and 32,000 to 51,000 deaths related to COVID -19. \nLong COVID remains a significant public health concern. 2023 national surveys estimated that \napproximately 9.2 million adults and 0.3 million children in the United States had long COVID. \nAmong adults, 3.6% reported current long COVID symptoms and 8.4% reported ever having \nlong COVID. Among children, 0.4% reported current symptoms, and 1.4% reported having the \ncondition at some point in their lives. More than three in five adults and nearly four in five children with long COVID reported experiencing activit y limitations due to their symptoms.  \nCOVID -NET, a population- based surveillance system that monitors laboratory -confirmed \nCOVID -19–associated hospitalizations, was used for the presentation. It is part of the \nRespiratory Virus Hospitalization Surveillance Network, along with RSV -NET and FluSurv -NET, \nand includes >300 hospitals in 185 counties across 13 states. The surveillance area represents approximately 10% of the U.S. population. Hospitalizations are included if a positive COVID -19 \ntest occurs within 14 days before admission or during hospitalization. Basic demographic data are collected for all patients, and detailed clinical data are gathered from a random sample \nstratified by age and site. Seasons are defined in the presentation as July 2024– June 2025 for \nrates, and clinical data reflect  the most recent 12 -month period, from April 2024 through March \n2025.  \nCOVID -19–associated hospitalization rates tend to peak both in the winter and the summer. \nThis pattern differs from RSV and influenza, which generally follow a more consistent seasonal trend with a single peak, typically in the winter. Cumulative COVID -19–associated \nhospitalization rates for the July 2024– May 2025 period were higher during summer and fall \n2024 and lower during the winter months compared to July 2023– June 2024. From July 2024 to \nApril 2025, a period that included a high severity influenza season, more infants <1 year and \nadults ≥75 years of age had hospitalizations associated with COVID -19 than influenza. \nCumulative COVID- 19-associated hospitalization rates are highest among adults aged ≥75 \nyears, followed by adults aged 65– 74 years and infants aged <6 months.  \nThe weekly number of COVID -19–associated deaths reported to the CDC in the United States \nfrom June 8, 2024, to June 7, 2025, showed a decreasing trend and remained low in the winter. Deaths during the winter were lower than those reported in the summer and fall of 2024. The \nnumber of deaths with COVID -19 listed as the underlying cause of death from July 2024 to June \n2025 showed that while COVID -19 causes deaths across all age groups, 70% occurred in \n5 \n adults aged 65 and older. Death certificate data likely underestimates COVID -19-associated \ndeaths. Among in- hospital deaths in patients with laboratory -confirmed SARS -CoV-2, the \nproportion with a COVID -19 cause of death listed decreased from 95% in 2020 to  60% in 2022–\n2023. CDC estimates that since October 1, 2024, between 32,000 and 51,000 people have died \nin the United States from COVID -19. \nThe highest rates for COVID -19 in the New Vaccine Surveillance Network were observed in \ninfants <6 months of age.  \nMore than half of pediatric COVID -19-associated hospitalizations in COVID -NET occur in \nchildren aged <2 years. COVID -19 causes severe disease in infants younger than 6 months, \nwho have the highest rates of COVID -19–associated hospitalization among all pedi atric age \ngroups. During July 2024 to May 2025, the cumulative COVID -19–associated hospitalization \nrate among infants was 268 per 100,000, comparable to the rate of 266 per 100,000 among \nadults aged 65– 74 years. As noted earlier in the presentation, hospit alization rates are higher \namong those aged >75 years and lower among those aged <65 years.  \nAmong infants <6 months old who were recently hospitalized for COVID -19, 22% were admitted \nto the ICU, 71% had no underlying medical conditions, and only 3.5% had any record of \nmaternal COVID -19 vaccination during pregnancy. No COVID -19 vaccine products ar e \napproved for use in infants <6 months, so any protection must come from transfer of maternal \nantibodies, either from vaccination during pregnancy or prior infection.  \nAmong vaccine- eligible children and adolescents ages 6 months –17 years, 41% of COVID -19-\nassociated hospitalizations occurred among children ages 6– 23 months.COVID -19-associated \ncumulative hospitalization rates are highest among the youngest age groups. The  youngest age \ngroups have comparable rates of cumulative COVID -19-associated hospitalization to some \nadult age groups, but direct comparisons are challenging. While most adults aged 50– 64 years \nadmitted for COVID -19 had underlying medical conditions, more than half of children aged 6– 23 \nmonths were otherwise healthy prior to their COVID -19 hospitalization.  \nAmong children aged 6– 23 months hospitalized for COVID -19, 54% had no underlying medical \nconditions. Among those with an underlying condition, the most common was prematurity. In the three older pediatric age groups (ages 2– 17 years), >70% of hospitalized children and \nadolescents had at least one underlying condition, with asthma or reactive airway disease and neurologic disorders being the most common. The proportion of hospitalized children with no \nunderlying medical conditions decreases with increasing age.  \nOne in four children aged <18 years hospitalized for COVID -19 required ICU admission. Among \nchildren <2 years who were admitted to the ICU, the majority (53%) had no underlying medical conditions. 89% of COVID -19 vaccine- eligible children and adolescents w ho were hospitalized \nwith COVID -19 had no record of receiving the most recent recommended COVID -19 vaccines.  \nFrom July 2024 to June 2025, the number of COVID -19–associated deaths among children <2 \nyears was similar to the number of influenza- associated deaths. Among children aged 2– 17 \nyears, influenza- associated deaths were higher. COVID -19 deaths are likely underestimated, as \npediatric flu deaths were nationally notifiable during this period, while pediatric COVID -19 \ndeaths were not.  \nSince March 2020, 128 COVID -19–associated deaths among children and adolescents have \noccurred within the COVID -NET catchment area, either during hospitalization or within 30 days \nafter discharge. Of the 25 pediatric deaths reported since July 2023, 10 occurred during the \nmost recent 12- month period from April 2024 through March 2025. These are raw counts, and \nthe COVID -NET catchment area represents approximately 10% of the U.S. population.  \n6 \n Among the 25 deaths since July 2023, 52% were in children <2 years, and 72% had at least \none underlying condition. Of the 16 children eligible for COVID -19 vaccination, 14 had no \nvaccination record, and none were up to date. Death certificate data reporting to COVID -NET is \ndelayed. Among the 25 most recent deaths with complete mortality data, 28% had COVID -19 \nlisted as a specific cause of death, while an additional nine deaths were attributed to other \nrespiratory or circulatory causes.  \nDr. MacNeil summarized that most pediatric COVID -19 hospitalizations occur in children <2 \nyears old, and many of these children have no underlying medical conditions, including 71% of \ninfants <6 months and 54% of children aged 6– 23 months. Hospitalization rates are highest \namong infants <6 months, followed by those aged 6– 23 months. Rates among infants <6 \nmonths of age are comparable to those of adults aged 65– 74 years. No COVID -19 vaccine \nproducts are approved for infants <6 months, so any protection must come from maternal \nantibody transfer through vaccination during pregnancy or prior infection.  Outcomes among \nhospitalized children can be severe, with 1 in 4 admitted to the ICU. COVID -19–associated \ndeaths continue to occur among infants and children, and the majority of hospitalized, vaccine -\neligible children and adolescents had no record of receiving the most recently recommended \nvaccine.  \nAdults ages ≥65 years comprise more than 2/3 of all COVID -19–associated hospitalizations \namong adults. Most adults hospitalized for COVID -19 have ≥1 underlying medical condition; a \nmajority have ≥2. Among adults hospitalized for COVID -19, 15% were admitted to the intensive \ncare unit (ICU). During this period, 85% of all adults hospitalized with COVID -19 who died in -\nhospital were ages ≥65 years.  \nMoving to COVID -19 hospitalizations among adults. Among adults hospitalized for COVID -19 \nfrom October 2024 through March 2025, vaccination status varied by age group. For adults \naged 65 years or older hospitalized for COVID -19, 65% had received neither the 2023– 2024 nor \nthe 2024– 2025 COVID -19 vaccine. One -third of the patients had received at least one dose of \nthe 2024– 2025 vaccine before admission, and 17% had received two doses.  \nPregnancy status was collected for women aged 15– 49 years who were hospitalized with a \nlaboratory -confirmed SARS -CoV-2 infection. Of those hospitalized, 28.5% were pregnant, and \n50% of these had COVID -19-related signs or symptoms. Among 131 hospitalized pr egnant \nwomen with confirmed infection and symptoms, 50% had no underlying medical conditions. At \ndischarge, 68% were no longer pregnant. Among these, 83% had a healthy newborn, 11% had \na preterm birth, 1% had an ill infant,  and 5% experienced pregnancy loss. Vaccination \ncoverage was low, with 92% having no record of receiving a COVID -19 vaccine since July 1, \n2023, and only 5.8% having received a recommended 2024– 2025 COVID -19 vaccine dose.  \nDr. MacNeil summarized the adult data by noting that rates of COVID -19–associated \nhospitalization are highest among the oldest adult age groups. Adults aged ≥65 years \naccounted for 72% of adult COVID -19—associated hospitalizations, and those aged ≥75 years  \nmade up 50%. Although hospitalization rates have decreased over time, cumulative rates \namong adults aged 75 years and older remain high. The risk of COVID -19–associated \nhospitalization continues year -round, with peaks in both winter and summer.  \nAmong adults aged ≥65 years hospitalized with COVID -19, 65% had no record of receiving one \nor more doses of the recommended 2024– 2025 COVID -19 vaccine before admission. Most \nadults hospitalized for COVID -19 had at least one underlying medical condition, and the majority \nhad two or more.  \n7 \n Among SARS- CoV-2-positive pregnant women admitted from April 2024 to March 2025 with \nCOVID -19–related symptoms at admission, half had no underlying medical conditions, and 92% \nhad no record of COVID -19 vaccination since July 1, 2023.  \nThe last part of the epidemiology presentation was on SARS -CoV-2 genomics. Since SARS -\nCoV-2 emerged in late 2019, the virus has continued to evolve with accumulating substitutions \nin the spike protein, which binds to the ACE2 receptor and is the main target for neutralizing \nantibodies. Over time, there have been periods of gradual genetic drift as well as more \nsignificant shifts when new lineages emerged with numerous changes.  \nThe first major shift occurred in late 2021 to early 2022, with the transition from the Delta variant \nto Omicron. Subsequent shifts included the emergence of XBB lineages from BA.4 and BA.5 \nviruses, and more recently from XBB to JN.1. These shifts necessit ated updates to the COVID -\n19 vaccine formulation to ensure continued protection.  \nIn winter 2023 -2024, we observed a strain replacement of XBB.1.5 -like viruses to JN.1 -like \nviruses. Since the emergence of JN.1, SARS -CoV-2 lineages have continued to evolve from this \nvariant, but no complete strain replacement has been observed. All lineages that have predominated since the emergence of JN.1 are currently descendants of JN.1.  \nLP.8.1, XFC, and NB.1.8.1 are JN.1 lineage viruses. When comparing amino acid substitutions \nin the spike protein to the 2024– 2025 COVID -19 vaccine formulation, there are only 2 to 4 \nchanges in the receptor binding domain. In contrast, circulating viruses l ast summer had 13 or \nmore changes in the spike receptor binding domain compared to the vaccine formulation at that time.  \nDr. MacNeil summarized that current circulating SARS -CoV-2 viruses are descendants of JN.1, \nwith 2 to 3 substitutions in the spike receptor binding domain compared to the KP.2 spike. \nThese viruses are effectively neutralized by serum from individuals who r eceived the 2024–\n2025 COVID -19 vaccine. Antigenic cartography shows that JN.1 viruses are antigenically \nsimilar. In May 2025, FDA’s VRBPAC reviewed genomic and phenotypic data and unanimously \nrecommended a monovalent JN.1 -lineage vaccine for the 2025– 2026 vaccine. FDA has advised \nmanufacturers to use a JN.1- based vaccine, preferentially using the LP.8.1 strain.  \nDr. Adam MacNeil (CDC/NCIRD) provided an update on vaccine effectiveness. For respiratory viruses, the CDC primarily uses case -control studies, including the test -negative design (TND), \nto measure vaccine effectiveness (VE). In the TND, individuals seeking care for respiratory \nillness are included. Cases are those who test positive for SARS -CoV-2, and controls are those \nwho test negative.  \nControls represent the population from which cases arise and help estimate COVID -19 vaccine \ncoverage among people seeking care for respiratory illness. By comparing vaccination status \nbetween cases and controls, we determine VE. Higher vaccine coverage among controls \nsuggests the vaccine provides protection. Because both groups sought care for similar \nsymptoms, this design helps reduce confounding factors, such as age and geography, thereby \nclarifying the relationship between vaccination and illness.  \nVE results were shared from three CDC platforms. The VISION Network, one of the platforms, \nencompasses data from over 300 emergency departments (ED) and urgent care (UC) clinics, as \nwell as more than 200 hospitals nationwide. It uses a test -negative design  to evaluate VE \namong individuals of all ages with COVID -19–like illness. Cases tested positive for SARS -CoV-\n2 and did not positive for RSV or influenza. Controls tested negative for SARS -CoV-2 did not \ntest positive for influenza or RSV, depending on age. Vaccination status is confirmed through \nelectronic health records and immunization registries.  \n8 \n The second VE platform, the Overcoming COVID -19 Network, focuses on children, with \nenrollment at 26 pediatric hospitals across 20 states. The analysis presented assessed the \neffectiveness of COVID -19 vaccination during pregnancy in preventing COVID -19–related \nhospitalizations in infants under 6 months of age.  \nThe third VE platform, the IVY Network, includes 26 hospitals across 20 states. Like VISION, \nIVY uses a test -negative design but with active enrollment, including patient interviews and \nnasal swabs. The analysis focused on adults aged ≥18 years hospitalized with COVID -19–like \nillness. Cases tested positive for SARS -CoV-2, while controls tested negative for SARS -CoV-2, \ninfluenza, and RSV. Vaccination history was determined through medical records, registries, \nand plausible self -report, with specimens collect ed for central testing and sequencing.  \nCOVID -19 VE measurement approaches have evolved over the years. Initially, absolute VE was \nused to compare outcomes in vaccinated versus unvaccinated individuals. During the bivalent \nvaccine era, relative VE was also measured, comparing outcomes between di fferent vaccine \ntypes (e.g., bivalent vs. original monovalent). For the 2023– 24 and 2024– 25 COVID -19 \nvaccines, VE estimates combine both approaches by comparing disease frequency in \nindividuals who received the current vaccine with that in individuals who did not, regardless of \ntheir prior vaccination or infection history. This method aligns with how seasonal influenza VE is \nmeasured and reflects the added benefit of annual vaccination.  \nCOVID -19 vaccination coverage in children remained low during both the 2023– 24 and 2024–\n25 seasons. Coverage was similar across both years, with the lowest rates observed among \nchildren aged 6 months to 4 years in the 2024– 25 season.  \nCOVID -19 vaccine uptake among adults aged ≥18 years was just under 25% by the end of \nAugust 2024 for the 2023- 2024 vaccine and the end of April 2025 for the 2024- 2025 vaccine. \nCoverage for the 2024– 2025 vaccine began increasing slightly earlier due to earl ier \nrecommendations and availability, but reached a similar overall level to 2023- 2024 coverage by \nthe end of April 2025.  \nAmong Medicare fee -for-service beneficiaries aged ≥65 years, overall COVID -19 vaccination \ncoverage for the 2024– 25 season reached 28% by January 2025. Coverage was highest in \nbeneficiaries with immunocompromising conditions (32%) and lowest in those without \nunderlying medical conditions (24%).  \nFor the 2023– 24 season, COVID -19 VE against ED and UC visits was evaluated through \nAugust 2024 in VISION. The reference group included individuals who did not receive a 2023–\n24 vaccine. For those aged ≥5 years, this included unvaccinated individuals and those who had \nonly received monovalent or bivalent doses. For children aged <5 years, both vaccinated and \ncomparison groups had to complete an initial series. VE was generally comparable across age \ngroups, with estimates for children being similar or higher than those for adults, consistent with \ntrends observed in previous seasons.  \nFor the 2024– 25 season, COVID -19 VE against ED and UC visits was assessed for the 7 to 179 \ndays post -vaccination period in VISION. Due to the lower number of COVID -19 cases, VE could \nnot be stratified by time since the doses were administered. Overall, VE appeared similar or \nhigher in children compared to adults, consistent with findings from the 2023– 24 season.  \nBetween March 2022 and May 2023, maternal COVID -19 vaccination was shown to be effective \nin protecting infants under 6 months of age from COVID –19–associated hospitalization, based \non data from the Overcoming COVID -19 Network. Infants in this age group are  not eligible for \nvaccination and are at higher risk of severe disease. VE was 54% during the first two months of \nlife and 35% during the first five months. Effectiveness declined with time since maternal \nvaccination, consistent with patterns seen in older  children and adults.  \n9 \n Among pregnant women aged 18– 45 years in VISION, COVID -19 VE against ED and UC visits \nwas highest when the dose was received during pregnancy, providing 52% protection. A dose \nreceived <6 months before pregnancy provided 28% protection, while a dose given ≥6 months \nbefore pregnancy was not statistically different from zero. These data, collected during 2022 \nand 2023 when Omicron was the dominant variant, reflect the pattern seen in non- pregnant \nadults and children, where more recent vaccination offers the greatest protection.  \nFor the 2023– 24 monovalent COVID -19 vaccines, VE in pregnant women (median 77 days \npost-vaccination) was similar to VE in non -pregnant women aged 18– 45 years (median 83 days \npost-vaccination) in VISION. Due to limited statistical power, VE by time since dose could not be \nassessed.  \nDuring the 2024– 25 season, COVID -19 VE against ED and UC encounters among adults aged \n≥18 years was 34% overall for the 7– 179 days following vaccination in VISION. VE was 36% for \n7–59 days, 35% for 60– 119 days, and 28% for 120– 179 days post -vaccination. VE  was similar \nbetween adults aged 18 –64 years and those aged ≥65 years. Among individuals in the \nreference group who did not receive a 2024– 25 COVID -19 vaccine, the median time since their \nlast dose was approximately 1,000 days.  \nCOVID -19 VE against hospitalization among adults aged ≥65 years without documented \nimmunocompromising conditions was similar in both the VISION and IVY networks. During the \n7–179 days after vaccination, VE was 44% in VISION and 46% in IVY. VE started at 46 % in \nVISION and 42% in IVY, declining to 32% and 40% respectively, during the 120- 179 days post -\nvaccination. Wider confidence intervals for later periods reflect smaller numbers of vaccinated \ncases and controls 4– 6 months before their encounter.  \nAmong adults aged ≥65 years, COVID -19 VE against critical illness remained relatively stable \nover time in both the VISION and IVY networks. In VISION, critical illness was defined as ICU \nadmission or in- hospital death. VE remained consistent even 120– 179 days after vaccination, \nsuggesting durable protection against severe outcomes. In IVY, VE during the 7– 179 days post -\nvaccination was assessed for three escalating outcomes: acute respiratory failure, ICU \nadmission or death, and invasive mechanical ventilati on or death. VE was highest for the most \nsevere outcome, with 70% protection against invasive mechanical ventilation or death.  \nAmong adults aged ≥65 years with immunocompromising conditions, COVID -19 VE against \nhospitalization during the 2024– 25 season was 38% in VISION and 36% in IVY. Although IVY \ndid not have sufficient statistical power to estimate VE by time since dose, VISION  appear to \nshow a trend of increasing VE over time. This pattern has been observed previously and is likely \ndue to faster waning of infection- induced immunity in immunocompromised individuals, making \nthe reference group less protected over time. VE in this  group was similar to that in non -\nimmunocompromised adults, indicating the vaccine is providing meaningful protection.  \nA sub -analysis from the IVY Network assessed COVID -19 VE against hospitalization by viral \nlineage, using whole genome sequencing to confirm KP.3.1.1 and XEC lineages. VE was calculated separately for each lineage, with controls defined as patients with COV ID-like illness \nwho tested negative for SARS -CoV-2, influenza, and RSV. VE was similar across lineages, with \noverlapping confidence intervals. Point estimates were 45% for KP.3.1.1 (median 56 days since \nvaccination) and 34% for XEC (median 87 days), with t he difference likely due to time since \nvaccination.  \nDr. MacNeil concluded that, for both the 2023– 24 and 2024– 25 seasons, in- season COVID -19 \nvaccination provided additional protection compared to no in- season dose. This included \nprotection against COVID -19–associated ED and UC visits among children and adul ts, \nhospitalizations among adults aged ≥65 years with and without immunocompromising \n10 \n conditions, and critical illness in older adults. Protection was generally similar across age groups \nand appeared to be higher and more durable for more severe outcomes.  \nVE should be interpreted as the added benefit of the 2023– 24 or 2024– 25 COVID -19 \nvaccination in a population with high levels of infection- induced, vaccine- induced immunity, or \nboth. Prior SARS -CoV-2 infection contributes to protection against future illness, but this \nprotection, like that from vaccination, wanes over time. Increased SARS -CoV-2 circulation in \nlate summer 2024, just before the approval of the 2024– 25 vaccines, may have raised \npopulation- level immunity against JN.1 lineage strains, potentiall y contributing to lower VE \nestimates during the season.  \nDr. Kulldorff asked about vaccine efficacy results from randomized, double- blind, placebo-\ncontrolled trials, which are considered the gold standard in medical research. He noted his appreciation for the focus on hospitalizations and deaths, emphasizing tha t these are the most \nimportant outcomes when evaluating COVID -19 vaccines.  \nDr. MacNeil responded that many of the randomized controlled trials were conducted in largely \nSARS- CoV-2 naïve populations, whereas the current context involves individuals with multiple \nexposures to vaccines, prior infection, or both. As a result, clinical trial data are not directly \ncomparable to present -day vaccine effectiveness estimates. Instead, current efforts focus on \nmonitoring the real -world impact of COVID -19 vaccines. Across age groups, the added benefit \nof recent vaccination has generally ranged from 30% to 50%, reflecting the value of continued \nvaccination in populations with existing immunity.  \nDr. Kulldorff responded by emphasizing the importance of having a control group that \nrepresents the general population in observational studies. He noted that this is best achieved \nthrough cohort studies. In case- control studies, controls should ideally be drawn from the \ngeneral population. He expressed concern about the test -negative design, where controls are \nindividuals with non- COVID respiratory illnesses, which may represent a distinct population with \ndifferent vaccination behaviors. He asked whether m ost of the presented results were based on \nthe test -negative design or if any were derived from cohort studies or traditional case- control \ndesigns.  \nDr. MacNeil acknowledged that case- control studies have limitations compared to traditional \ncohort studies. He explained that all platforms used for the presented data rely on case -control \ndesigns, with most using a test -negative design. This approach allows for efficient data \ncollection in large populations without being cost -prohibitive. He noted that with sufficient \nsample sizes, these designs can produce relatively accurate estimates of VE.  \nDr. Meissner raised a concern about the definition of COVID -19–associated hospitalizations \nused in the data. He noted that many slides referenced hospitalization rates based on a positive RT-PCR test for SARS -CoV-2 but emphasized that this does not necessarily mean the patient \nwas hospitalized due to COVID -19. He pointed out that being hospitalized with COVID -19 is \ndifferent from being hospitalized for COVID -19. Citing a study previously conducted by the \nCommonwealth of Massachusetts, he mentioned that less  than half of patients with a positive \ntest were being treated for COVID -19, suggesting that the presented hospitalization numbers \nmay overestimate the burden of severe COVID -19 illness.  \nDr. Taylor explained that COVID -NET comprises two components: population- based \nhospitalization rates based on laboratory -confirmed SARS -CoV-2 positive tests, and clinical \ndata from a filtered sample of hospitalizations. While the rates include all lab- confirmed cases \nregardless of the reason for admission, the clinical data focus only on hospitalizations where \nCOVID -19 was identified as the likely cause. He noted that this distinction is reflected in the \nfootnotes on the slide. Dr. Taylor also referenced a peer -reviewed study published in Influenza \n11 \n and Other Respiratory Viruses , which found that during the 2022– 2023 period, 86 percent of \nadult hospitalizations with lab- confirmed COVID -19 were attributable to the virus. Attribution was \nbased on factors such as illness related to COVID -19 at admission, treatment during \nhospitalization, or discharge diagnoses indicating conditions like pneumonia or ARDS.  \nDr. Meissner responded by noting that the severity of COVID -19 has decreased since the 2022–\n23 period. He acknowledged that hospitalization rates are now much lower. He suggested that \nthis could be due to viral mutations leading to less severe illness, inc reased population- level \nimmunity from vaccination or prior infection, or a combination of both. He also raised a similar \nconcern regarding COVID -19–associated deaths, questioning how many occurred in individuals \nwith symptoms consistent with a viral infect ion versus those who were classified as COVID -19 \ncases solely due to a positive test upon hospital admission, as some hospitals require routine \ntesting for all admitted patients.  \nDr. Taylor responded that this is an important question and shared that an analysis is currently \nunderway to examine deaths using the most recent years of death certificate data. The team is \nin the mid- stages of this work and plans to present its findings to ACIP once they are available. \nHe also noted that, early in the pandemic, all hospital admissions were routinely screened for \nCOVID -19; however, this is no longer standard practice in most hospitals. Preliminary data from \nthe 2021– 22 and 2022– 23 seasons suggest that the proportion of hospitalizations attributable to \nCOVID -19 has slightly increased over time. This is likely due to reduced screening, meaning \nthat those now tested for COVID -19 are more likely to have symptoms consistent with COVID -\n19 illness , rather than being asymptomatic.  \nDr. Meissner noted that, based on the most recent CDC data, hospitalization rates for children \naged 0– 4 years are less than one per 100,000. For children under six months, the rate is \napproximately 1.6 per 100,000. He asked if this was an accurate interpre tation and emphasized \nthat, in his view, COVID -19 is currently a very rare cause of hospitalization in both young \nchildren and adults.  \nDr. MacNeil responded by emphasizing the importance of considering overall cumulative \nnumbers, noting that COVID -19 continues to pose a substantial burden, particularly among the \nyoungest and oldest age groups. He added that comparisons to influenza, as shown in the \nearlier slides, highlight that COVID -19 still presents areas for concern.  \nDr. Meissner questioned whether Dr. MacNeil felt the rates were accurate.  \nDr. MacNeil emphasized that COVID -NET has been a robust platform, capturing data from \napproximately 10% of the U.S. population and allowing for strong characterization of illness. He \nnoted that while modeled national estimates based on this data come with some uncertainty, the \nconfidence intervals are reasonable, and the resulting burden estimates fall within a reliable and \nconsistent range.  \nDr. Meissner commented on the reference to influenza, noting that while early comparisons between COVID -19 and influenza were common, including himself, it has become clear that the \ntwo viruses behave quite differently. He explained that orthomyxoviruses, like influenza, differ \nfrom coronaviruses in how they mutate and spread. He referred to the concepts of antigenic \nshift and drift, suggesting that continued comparisons may not be appropriate, as the viruses \nare fundamentally different.  \nDr. MacNeil acknowledged Dr. Meissner’s point, clarifying that the intent was not to suggest that \nthe pathophysiology of influenza and COVID -19 are the same, but rather to compare the overall \npopulation burden. He agreed that it's a valid distinction. He added that it may also be \nappropriate to consider using different terminology for COVID -19, rather than borrowing terms \nlike \"drift\" and \"shift\" from influenza. He explained that the key point is the observation of large, \n12 \n sudden changes in circulating COVID -19 variants that allow the virus to evade pre -existing \nimmunity. He noted that it may be worth further discussion with influenza experts about adopting \nmore accurate terms for these rapid changes in dominant COVID -19 var iants.  \nDr. Levi questioned the test -negative design, noting that it compares the proportion of \nvaccinated individuals among SARS -CoV-2–positive patients with those who test negative. He \nproposed that a lower vaccination rate in the positive group might still be c onsistent with \nvaccines increasing overall susceptibility to multiple respiratory viruses, with vaccinated people appearing in both groups but slightly less often among the positives. Such a scenario, he \nargued, could create the appearance of vaccine effec tiveness even if vaccination provides no \nbenefit or increases vulnerability. He added that some of the data presented suggest this may be occurring, as the rate of hospitalization among people with updated vaccination appears \nhigher than their relative proportion in the general population. He stated this should raise \nconcern and prompt further consideration of alternative explanations beyond vaccine efficacy.  \nDr. Link -Gelles explained that the goal of the TND is to use controls that represent the \nvaccination coverage in the population from which the cases originated. A key strength of TND \nis that controls have the same symptoms as the cases and seek care and testing at the same \nfacilities, making them population- based in this context. She emphasized that while the controls \nare not representative of the general population, they are representative of individuals who \nwould have been hospitalized if they had COVID -19. In this analysis, controls are often older \nadults hospitalized with acute respiratory illness, so their vaccination coverage would not be expected to match that of the broader, generally healthier U.S. population. Due to this design, \nthe controls are considered suitable for estimating the relative impact of vaccination.  \nDr. Hoeg expressed concerns about the potential for confounding in the test -negative design, \nechoing the points raised by Dr. Kulldorff and Dr. Levi. She questioned why patients who test positive for influenza and, in people aged ≥60 years, RSV, are excluded if the goal is to \ncompare groups with similar symptoms, with one group testing positive for COVID -19 and the \nother not. She noted that these groups may differ in meaningful ways, making it difficult to ensure they are truly comparable. Dr. Hoeg emphasiz ed the importance of randomized \ncontrolled trials in minimizing bias and avoiding uncertainty about whether observational data \naccurately reflects VE.  \nDr. Link -Gelles responded that including individuals who test positive for another vaccine-\npreventable disease as controls or cases could introduce bias into the study. She explained that \nvaccine status is correlated across diseases, and individuals who test positive for influenza or \nRSV are often less likely to have received those vaccines, which also makes them less likely to \nhave received the COVID -19 vaccine. This correlation can distort the results. She cited \npublished literature supporting this concer n and explained that, for this reason, controls who test \npositive for influenza or RSV are excluded. She also noted that the study teams work closely \nwith sites to ensure that cases and controls have similar symptoms, and they have analyzed \nand published data confirming that symptom profiles and severity are balanced between groups.  \nDr. MacNeil added that while randomized clinical trials are valuable, there are real -world \nlimitations related to time and cost. He emphasized that the test -negative design provides a \nrobust and efficient method for generating real -world vaccine effectiveness data promptly. For \nexample, reviewing VE data from the most recent season in June would not be feasible using \nrandomized trials due to the time required for enrollment, follow -up, and analysis. He noted that \nfor the CDC, the test -negative design is a p ractical and effective approach to assess the real -\nworld impact rapidly.  \nDr. Levi commented on the genomic evolution of SARS -CoV-2 variants, noting that while there \nis continuous evolution, two major jumps stand out. He raised two questions related to this \n13 \n observation. First, he asked whether any analysis has been done to compare this pattern to \nother viruses, such as influenza, to determine how common such large evolutionary jumps are. \nSecond, he inquired about the evolutionary pressures that might be drivi ng these shifts, as such \nchanges typically result from natural selection. He also questioned whether there has been any \nanalysis of a possible connection between vaccination policies and the observed evolution of \nthe variants, noting that the pattern appears striking.  \nDr. MacNeil responded that the evolution of COVID -19 has indeed been full of surprises, with \nthe emergence of major variants, such as Omicron, representing sudden and significant changes. He noted that these large shifts likely reflect a combination of sel ective pressures \nwithin the human population, such as pre- existing immunity, as well as unique characteristics of \nthe virus itself. He emphasized that the situation is complex and dynamic. Dr. MacNeil also \nemphasized the importance of ongoing genomic surveillance and real -time sequencing, which \nenable experts to detect and monitor variant changes as they emerge. He emphasized the \nimportance of maintaining this capacity to respond quickly to any unexpected shifts in the virus.  \nDr. Meissner added to the discussion by noting the increasing complexity of SARS -CoV-2 \nevolution, particularly the emergence of convergent evolution, where different strains develop \nthe same mutations in specific regions of the spike protein. He emphasized that this makes the \nsituation even more challenging to analyze. Shifting to the topic of study design, Dr. Meissner \nacknowledged that the case- control approach, including the test -negative design, is not perfect \nand carries certain limitations, such as a potential bias toward individuals who are more likely to seek medical care. However, he pointed out that it remains the most practical option for \nevaluating vaccine effectiveness within a limited timeframe, as is done with influenza vaccines, \nwhich are updated annually. He concluded that, despite its flaws, the case- control design is a \nwell-established method for evaluating vaccines.  \nDr. Kulldorff emphasized the importance of distinguishing between traditional case- control \nstudies and the test -negative design. He noted that, methodologically, these are very different \napproaches and that the quality of the information they produce can v ary significantly.  \nDr. Taylor clarified a question regarding the COVID -NET hospitalization rates presented earlier \nby Dr. MacNeil. He explained that the figures shown on the slides represent cumulative rates, \nwhich are the sum of weekly hospitalization rates over a period fr om July 2024 through May \n2025. For children <6 months, the cumulative hospitalization rate was 268 per 100,000, \ncomparable to the rate among adults aged 65 to 74 years. For children aged 6 to 23 months, \nthe cumulative rate was 100 per 100,000, similar to t he rate for adults aged 50 to 64 years, \nwhich was 103 per 100,000. Dr. Taylor emphasized that while weekly rates may seem small, \nthe cumulative rates provide a more accurate picture of disease burden over time.  \nDr. Levi asked whether the proportions of COVID -19–associated hospitalizations by age group \ndiffer from overall hospitalization patterns for all causes. Specifically, he questioned whether the \ndistribution seen here deviates from general hospitalization tr ends across age groups or if it is \nconsistent with typical patterns.  \nDr. Taylor responded that COVID -NET, as one of the RESP -NET platforms, is specifically \ndesigned to collect data on SARS -CoV-2–positive, COVID -19–associated hospitalizations. As \nsuch, it does not include data on all -cause hospitalizations and cannot be used to directly \ncompare COVID -19 hospitalization rates to general hospitalization rates across age groups. He \nnoted that while previous ACIP meetings have included analyses comparing underlying conditions among adults hospitalized with COVID -19 to those in the general population, COVID -\nNET data do not support comparisons between COVID -specific and general hospitalization \npatterns.  \n14 \n Dr. Sarah Meyer (CDC/NCEZID) shared an update on how the CDC monitors vaccine safety. \nThe CDC and interagency partners launched a comprehensive vaccine safety monitoring \nprogram for COVID -19 vaccines. A wide range of potential safety outcomes has been rigo rously \nassessed through complementary passive and active surveillance systems. Myocarditis has \nbeen causally linked to mRNA COVID -19 vaccines. Common adverse events, such as local and \nsystemic reactions and allergic responses, have also been observed. The CDC continues to \nactively monitor the safety of COVID -19 vaccines.  \nVaccine safety monitoring is essential throughout the vaccine life cycle, from early research and \nclinical trials to regulatory review. After a vaccine is authorized or approved, the CDC begins \nsafety monitoring in coordination with the FDA, the Indian Health Service, the Department of \nDefense, and the Department of Veterans Affairs.  \nThe CDC employs a robust, complementary system of layered safety monitoring to promptly \nidentify and evaluate potential concerns, enabling public health officials and policymakers to \ntake timely action. Most systems have been in place for decades, but the CDC continues to \nimprove existing systems and develop new ones to fill gaps, such as v -safe, which was \nlaunched to monitor the safety of COVID -19 vaccines.  \nThe Vaccine Adverse Event Reporting System (VAERS) is the nation's early warning system for \nvaccine safety, co -managed by the CDC and the FDA. It relies on spontaneous reports from \nacross the country to detect potential safety signals, including rare event s. Healthcare providers \nand manufacturers are required by the National Childhood Vaccine Injury Act to report certain \nadverse events; however, patients or their family members can also submit reports. It's essential \nto note that reporting an event to VAERS  does not necessarily mean that the vaccine caused it. \nVAERS is used for signal detection and hypothesis generation, not to determine causality.  \nThe Vaccine Safety Datalink (VSD) is a collaborative system that generates high- quality data on \nvaccine safety. It includes 13 integrated healthcare organizations and serves approximately \n15.5 million people annually. VSD uses active surveillance through electronic medical records \nand chart reviews, enabling rapid monitoring of both prespecified and unexpected events. \nUnlike VAERS, which is primarily used for signal detection, VSD can detect and assess safety \nsignals. The network is also known for its strong expertise, which has led to the development of \ninnovative methods for monitoring vaccine safety.  \nThe Clinical Immunization Safety Assessment (CISA) Project is a network that supports vaccine \nsafety from the individual to the population level. It includes eight medical research centers with \nvaccine safety experts and specialists. CISA provides clinical  consultations on complex \nimmunization issues to support patient care and research real -world vaccine safety questions \nnot addressed in pre -licensure trials. CISA consultants also help inform the CDC’s public health \nguidance on clinical immunization safety  issues.  \nV-safe After Vaccination Health Checker is the CDC’s newest tool for direct -to-consumer \nvaccine safety monitoring. It is a smartphone and web- based, self -reported active monitoring \nsystem established during the COVID -19 pandemic. v -safe can provide early i nformation on \nreactogenicity and other health events, especially for new vaccines and populations not \nincluded in clinical trials. For example, it helped enroll over 23,000 pregnant women into a \nvoluntary registry to monitor maternal and neonatal outcomes after COVID -19 vaccination. V -\nsafe is flexible, quickly deployable, and plays a key role in emergency preparedness and response. It is also integrated with VAERS to streamline reporting serious adverse events.  \nThese systems support the CDC’s comprehensive approach to COVID -19 vaccine safety, which \nincludes surveillance of reported events, epidemiologic studies, clinical research, and a pregnancy registry. The approach also utilizes rapid cycle analysis, data mining of over 60,000 \n15 \n outcomes, and patient surveys to identify and assess potential safety concerns and health \nimpacts following vaccination.  \nAn overview of the extensive body of evidence on COVID -19 vaccine safety was provided. \nSince the rollout in December 2020, data have been documented in 17 Vaccine Safety \nTechnical Work Group reports, 28 presentations to federal advisory committees, 29 publ ications \nin the MMWR, 114 peer -reviewed manuscripts, and through nearly 10 million participants \nenrolled in v -safe. This information was collected during the largest vaccination effort in U.S. \nhistory, with approximately 1 billion doses distributed.  \nDr. Meyer recapped that three types of COVID -19 vaccines were authorized or approved for use \nin the United States: mRNA vaccines by Pfizer -BioNTech and Moderna, a protein- based \nvaccine by Novavax, and a viral vector -based vaccine by Janssen. The use of the  Janssen \nvaccine became limited in April 2021 after the VAERS system detected six reports of thrombosis with thrombocytopenia syndrome (TTS). In response, the FDA and the CDC issued \na 10- day pause in its use. By December 2021, ACIP issued a preferential recommendation for \nmRNA vaccines, and in June 2023, the EUA for Janssen was revoked. The vaccine is no longer in use in the United States. This situation highlighted how federal safety systems worked \ntogether to identify and address a concern regarding vacci ne safety promptly.  \nDr. Meyer noted that post -authorization safety data for Novavax remain limited due to its later \nauthorization in July 2022 and low uptake in the U.S. Therefore, the remainder of the discussion \nfocused on the safety of mRNA COVID -19 vaccines, which are supported by a large and \ngrowing body of evidence.  \nThe CDC has evaluated at least 65 specific outcomes to assess the safety of the COVID -19 \nvaccine using a variety of systems and epidemiologic methods. Since December 2020, weekly \nrapid cycle analyses (RCAs) in the Vaccine Safety Datalink have tracked up to  23 prespecified \noutcomes in over 12 million people, based on clinical trial data, known vaccine risks, and \nbiological plausibility.  \nAutomated statistical testing compares rates of outcomes in post -vaccination risk intervals with \nthose in comparison periods. When a signal is detected, further analysis or chart review is \nconducted. The system is designed to be sensitive, and not all signals indicate a true safety \nconcern.  \nBetween 2020 and 2025, eight statistical signals were identified through VSD’s weekly rapid \ncycle analyses. These included acute myocardial infarction, venous thromboembolism, immune \nthrombocytopenic purpura, ischemic stroke, seizure, Guillain- Barré syndro me, Bell’s palsy, and \nmyocarditis.  \nWhen a signal is detected, the CDC conducts further investigations to determine if it reflects a true safety concern or a false positive. These follow -up steps include chart reviews, trend and \ncluster analyses, additional studies such as self -controlled case series, and a review of data \nfrom other monitoring systems, including VAERS and partner databases managed by the FDA \nand VA.  \nAfter completing these investigations, the CDC determined that there is an increased risk of \nmyocarditis following mRNA COVID- 19 vaccination. No clear or consistent evidence of a safety \nconcern was found for the other outcomes mentioned.  \nUsing data from the Vaccine Safety Datalink, the CDC assessed the incidence of myocarditis \nwithin seven days of COVID -19 vaccination among individuals aged 12– 39 years, by season \nand dose. Rates were highest in males, peaking among those aged 16– 17 years. Myocarditis \nwas rare in children <12 years and in adults >50 years. The risk was highest after the second \n16 \n dose in the primary series but remained elevated after the first monovalent booster. In later \nseasons, incidence declined and approached the background rate of <2 cases per million. \nSimilar patterns have been observed in VAERS reports. Several factors may explain the decline \nin myocarditis rates in recent years, including increased overall population immunity, a longer \ninterval between doses, and fewer people receiving more than one dose per year.  \nThe FDA recently shared updated data on myocarditis and pericarditis following mRNA COVID -\n19 vaccination from the Biologics Effectiveness and Safety (BEST) system during the 2023–\n2024 season. In April, the FDA issued safety labeling change notification let ters to vaccine \nmanufacturers, instructing them to include new information on myocarditis and pericarditis. FDA \napproved safety labeling updates for Comirnaty and Spikevax to reflect this new safety \ninformation.  \nCDC follow- up studies show that most adolescents and young adults have recovered from \nmyocarditis after receiving an mRNA COVID -19 vaccine. These studies included individuals \naged 12– 29 years with a VAERS report filed between January and November 2021, along with \ninput from their healthcare providers. Based on assessments by cardiologists or other providers, 83% were considered fully or probably recovered within 90 days of symptom onset, and by one \nyear, at least 90% had recovered.  \nMost individuals showed improvement in symptoms, as well as in cardiac imaging and testing \nresults. A subset who underwent cardiac MRI one year after onset most commonly showed late \ngadolinium enhancement, which may suggest the presence of fibrosis. However, the clinical \nsignificance of this finding is unclear, as most were considered recovered and had been cleared \nfor all activity. There were no known deaths or cardiac transplants in this group.  \nCOVID -19 vaccine safety data for children aged 6 months to 11 years show a low risk of \nmyocarditis, particularly in those under 5 years. No statistical signals for myocarditis have been \ndetected in the Vaccine Safety Datalink, and no confirmed cases have been reported in VAERS \nor the VSD for children under 5. VSD rapid cycle analyses also found no increased risk for 22 \nother prespecified outcomes. Most cases of MIS -C after vaccination had evidence of prior \nSARS- CoV-2 infection.  \nThe majority of COVID -19 vaccine reports submitted to VAERS for children <12 years were \nrelated to vaccine administration errors. From October 2021 to April 2025, approximately 74% of \nreports for children aged 6 months to 4 years and 70% for those aged 5 t o 11 years involved \nerrors, such as expired product, incorrect dose or formulation, administration to the wrong age \ngroup, or preparation issues. Few of these reports included an actual adverse event. The high \nnumber of administration error reports likely reflects the complexity of the pediatric COVID -19 \nvaccination program, particularly early in the rollout when dosing, recommendations, and \nstorage requirements varied by product. CDC is expanding its efforts to prevent vaccine \nadministration errors in coll aboration with the FDA.  \nCDC has actively assessed the safety of COVID -19 vaccines in pregnant women through \nmultiple efforts. A voluntary pregnancy registry enrolled over 23,000 pregnant participants to \nmonitor outcomes. Additionally, the CDC has conducted seven observational studies using \nsurvey and medical record data. In the Vaccine Safety Datalink, over 45,000 pregnant women \nhave been evaluated through 11 cohort, case- control, and surveillance studies to date.  \nAcross these CDC studies, the evidence shows no increased risk of adverse maternal outcomes associated with COVID -19 vaccination, including 25 medically attended adverse \nevents, serious acute events, pregnancy -related conditions, or maternal ICU admissions . \nVaccination was also not associated with adverse pregnancy outcomes such as miscarriage, \n17 \n stillbirth, preterm birth, or small for gestational age. Additionally, no association was found \nbetween maternal vaccination and major birth defects, neonatal ICU admission, or infant death.  \nThe CDC has conducted studies to address public concerns about the safety of the COVID -19 \nvaccine. In response to reports of abnormal uterine bleeding, analyses using VAERS, VSD, and \nv-safe found no association between vaccine availability and the incidenc e of medically \nattended abnormal uterine or postmenopausal bleeding. The vaccine was also not linked to \nincreased bleeding severity. CDC also assessed reports of tinnitus using data from VAERS and \nVSD. No safety signals were detected, and findings did not support an increased risk of tinnitus \nfollowing COVID- 19 vaccination.  \nCDC monitors death reports following mRNA COVID -19 vaccination through VAERS. As of May \n30, 2025, 19,417 domestic deaths had been reported after vaccination. Under FDA emergency \nuse authorizations and CDC provider agreements, healthcare providers were required to report \nall deaths occurring within 30 days after COVID -19 vaccination, regardless of cause or \ncircumstances. This requirement does not apply to other vaccines.  \nVAERS is not designed to assess causality. CDC evaluated deaths reported following mRNA \nCOVID -19 vaccination through January 31, 2023. During this period, the CDC received 17,631 \ndomestic VAERS reports of death following COVID -19 vaccination. After clinical review, 52 were \nexcluded as they did not represent actual deaths, 1,790 involved non -mRNA vaccines, and \n2,940 lacked a confirmed cause of death.  \nThis left 12,849 reports with confirmed causes of death, identified through autopsy, death \ncertificate, medical records, or the VAERS report. Among these, 78% were aged ≥65 years, \n15% were 50– 64, 6% were 18– 49, and 5% were <18 years.  \nCDC assessed all reported deaths in the general U.S. population during this period using death \ncertificate data from the National Center for Health Statistics' multiple cause of death database, \ncategorized by ICD -10 codes. Observed- to-expected ratio analys es were conducted for each \nage group by comparing the number of cause -specific deaths reported to VAERS within 42 days \nof mRNA COVID- 19 vaccination to the number of expected deaths in the general U.S. \npopulation.  \nCDC found that reported death rates after mRNA COVID -19 vaccination were below \nbackground rates in the general U.S. population. The most common causes of death reported to \nVAERS, such as heart disease, COVID -19, cerebrovascular disease, and general signs and \nsymptoms like shock, were consistent with the leading causes of death nationally. In children, congenital malformations were also reported, and among adults aged ≥18 years, malignant \nneoplasms were included.  \nAcross all age groups, the observed -to-expected death ratio was <1, indicating fewer reported \ndeaths than expected within 42 days of vaccination. Despite the limitations of VAERS, these \nfindings suggest no association between mRNA COVID -19 vaccination and increased mortality.  \nIn addition to reviewing VAERS reports, the CDC conducted two self -controlled case series \nevaluations using the Vaccine Safety Datalink, one in the general population aged 12 years and older and one in Medicare beneficiaries aged 65 years and older. Pfizer  and Moderna vaccines \nwere analyzed separately. Both studies found no increased risk of non -COVID -19 mortality, all -\ncause mortality, cardiac -related mortality, or non- COVID -19 cardiac -related mortality within 28 \ndays following vaccination. Relative incidence rates were significantly <1 in all cases.  \nThese findings are consistent with results from a separate cohort analysis in the VSD. The \nrobust methods used across these analyses provide strong evidence of no increased risk of \ndeath after mRNA COVID -19 vaccination and suggest a potential protective ef fect. \n18 \n CDC uses data mining in the Vaccine Safety Datalink to detect unexpected adverse events \nfollowing COVID- 19 vaccination. This approach evaluates over 60,000 possible outcomes within \n70 days of vaccination using tree -based analysis of ICD -10 codes. Assessments have been \nconducted for the primary series, initial booster, and bivalent booster. No new safety concerns \nhave been identified beyond known events such as myocarditis, pericarditis, allergic reactions, \nand common local or systemic reactions.  \nDr. Meyer summarized that several adverse events have been identified following mRNA \nCOVID -19 vaccination. Most, such as local and systemic reactions, acute allergic reactions, \nsyncope, and shoulder injuries, are common to many vaccines. Myocarditis and pe ricarditis \nhave also been observed specifically following COVID -19 vaccination. These conclusions are \nbased on the evaluation of at least 65 specific safety outcomes, data mining of over 60,000 \npotential outcomes, investigation of multiple statistical signals, and numerous epidemiologic \nstudies.  \nThese findings align with the National Academies of Sciences, Engineering, and Medicine's \nconsensus report on the adverse effects of COVID -19 vaccines, commissioned by HRSA and \npublished in 2024. The report reviewed over 400 studies on vaccine safety. It c oncluded that \nthere is evidence supporting a causal association between mRNA COVID -19 vaccines and \nmyocarditis. It also found that the evidence favors rejecting a causal link between vaccination \nand six other outcomes: Guillain- Barré syndrome, Bell’s palsy , TTS, myocardial infarction, \nischemic stroke, and female infertility. For 13 other outcomes, the evidence was deemed inadequate to accept or reject a causal relationship.  \nCOVID -19 vaccines have been evaluated under the most extensive vaccine safety monitoring \nprogram in U.S. history. This surveillance quickly identified and characterized the risk of myocarditis following mRNA vaccination. No other confirmed safety concerns have been \nidentified beyond those commonly seen with other vaccines, such as local reactions, systemic \nsymptoms, or allergic responses. CDC continues to prioritize COVID -19 vaccine safety, with at \nleast 30 ongoing studies or monitoring activities.  \nDr. Hibbeln stated that he has long been interested in risk -benefit evaluations and asked \nwhether a broad summary of the data presented would be accurate. He noted that the evidence \nsuggests a minimal to no risk of death from receiving a COVID -19 vaccine, whereas Dr. \nMacNeil’s presentation indicated a substantial risk associated with not being vaccinated. He \nasked whether it would be reasonable to describe the benefit of vaccination as a 40-  to 50 -\npercent reduction in risk, with essentially zero risk of death from the vaccine. He framed this as \na general assessment of the overall risk -benefit balance.  \nDr. Meyer responded that several studies have been conducted to evaluate the risk of mortality \nfollowing COVID- 19 vaccination, and no increased risk has been observed. In VAERS analyses \ncomparing observed to expected deaths, the data did not show a higher -than-expected number \nof deaths. Similarly, evaluations using the Vaccine Safety Datalink found no increased risk of \nmortality after vaccination. From a safety perspective, the data support confidence that COVID -\n19 vaccines are not associated with an increased risk of death. Regarding the overall risk -\nbenefit assessment, Dr. Meyer noted interest in hearing the committee’s evaluation of those \nfactors.  \nDr. MacNeil added a rough estimate to illustrate the potential impact of vaccination on COVID -\n19 mortality. Using a hypothetical scenario, if there were about 40,000 COVID -19-related deaths \nin a year and none of those individuals had been vaccinated, then applying the observed \nvaccine effectiveness, approximately half, or about 20,000, of those deaths might have been \nprevented. This was presented as a general approximation to highlight the potential benefit of \nvaccination in reducing deaths.  \n19 \n Dr. Malone asked for clarification on the safety monitoring timeframes presented. Specifically, \nthe question focused on whether the post -vaccination periods, defined as either 28 days or 42 \ndays, apply to individuals who have completed at least two doses. Dr. Malone requested \nclarification on how \"post -vaccination\" is defined in the context of the data that was shared.  \nDr. Meyer responded that the analyses included individuals who had received at least one dose \nof a COVID -19 vaccine. For the VSD analyses, three separate evaluations were conducted: one \nafter completion of the primary series, one following the original booster, and one after receiving \nthe Omicron booster.  \nDr. Malone followed up by asking whether the analysis of adverse event associations, like the \nmortality analysis, was also limited to a 28- day post -vaccination window.  \nDr. Weintraub explained that analyses for the Vaccine Safety Datalink were set up to examine \n21-day and 42- day risk intervals following doses one and two of the primary series. This \napproach has been consistently applied with each new vaccine recommendation, including the \nmost recent season. The 42- day window also allows for scanning of shorter time intervals within \nthat period to identify potential clusters of increased risk, using Martin Kulldorff’s clustering method. It is standard practice to use a 42 -day risk interval and to compare it to a historical \ncontrol period, typically days 43 to 84 after vaccination.  \nDr. Malone commented on the presentation of the adverse events assessed, noting that the slide listing the 65 outcomes was difficult to interpret. He suggested that it would be helpful if the \ninformation were structured more clearly, such as in alphabetical order, to better understand the \nfull range of events evaluated. Based on his review, he inferred that hypertension, tachycardia, \nand POTS were included in the analyses and were not found to be associated with COVID -19 \nvaccination.  \nDr. Meyer responded by explaining that both VAERS and the Vaccine Safety Datalink (VSD) use prespecified lists of outcomes to monitor and flag for further review. In addition to tracking \nprespecified outcomes, VSD also investigates other emerging concerns as needed.  \nDr. Meyer acknowledged that the slide listing the 65 outcomes was intended to provide a brief \noverview and could be made clearer. A more detailed list can be shared if needed. She also \nnoted that data mining is used to detect unexpected outcomes without specifying them in \nadvance. None of the conditions mentioned, including POTS, appeared as signals in the data \nmining. While some studies on outcomes, such as POTS, have been referenced in the National \nAcademies report, the available data are limited. Based on the CDC’s comprehensive approach, \nincluding both targeted analysis and broad surveillance, the primary safety concerns identified \nremain myocarditis and common vaccine- related reactions.  \nDr. Malone emphasized the public’s need for transparency and recommended that a clear, \ncomprehensive list of all safety outcomes and analyses be made publicly available. He also \nasked whether potential lot -to-lot variability in vaccine manufacturing had been examined, \nnoting that such variability could mask clusters of adverse events when data are viewed in \naggregate, and requested details on how this issue has been addressed.  \nDr. Meyer responded that the CDC works closely with interagency partners on vaccine safety, \nwith each agency having distinct roles. She noted that lot -specific issues are typically assessed \nby the FDA and deferred to FDA colleagues for any additional infor mation on that topic.  \nDr. Meissner emphasized that physicians are trained to report any adverse event (AE) after \nvaccination to VAERS, regardless of causality. Given the high volume of vaccinations, many \nreported AEs are unrelated to the vaccine. He clarified that VAERS is not used to determine \nincidence rates but to detect safety signals, which are then evaluated further using systems like \n20 \n VSD. He noted most VAERS reports do not indicate a causal relationship. Dr. Meissner then \nasked Dr. Meyer about the long- term follow- up of myocarditis cases, particularly regarding \nindividuals with late gadolinium enhancement on cardiac MRI, which may suggest scarring and \npotential risk for arrhythmias or sudden death. He also inquired about data from manufacturers \non troponin levels and markers of subclinical myocarditis, which he understood had been \nrequested but had not yet been reported.  \nDr. Meyer responded that some studies have evaluated subclinical myocarditis, including those \nthat measure biomarkers such as troponin in asymptomatic individuals. These studies have not \nshown adverse clinical outcomes in those cases. However, the long -term significance remains \nuncertain and requires ongoing monitoring. CDC is closely tracking this issue, and FDA is conducting similar studies with comparable findings. This information is expected to be included \nin upcoming safety labeling updates, and both the CDC and the FDA plan to continue long -term \nmonitoring.  \nDr. Levi questioned whether traditional vaccine safety surveillance methods, which focus on \nshort -term adverse events, are sufficient for COVID -19 vaccines, given evidence that residual \nmRNA and spike protein may persist in the body for months. He suggeste d this could reduce \nthe sensitivity of current approaches and called for broader methods. He cited a VA study \nshowing higher adverse events with Pfizer compared to Moderna. He emphasized the \nimportance of accounting for factors like the healthy vaccinee ef fect when comparing mortality \nrates. He asked whether surveillance systems are adapting to address the unique characteristics of COVID -19 vaccines.  \nDr. Meyer responded that the United States has one of the strongest vaccine safety systems in the world and expressed confidence in its current approach. However, efforts are ongoing to identify ways to improve the system, especially in monitoring long- term outcomes after \nvaccination. She noted that detecting long- term effects is challenging because, over time, \nconfounding factors such as infections or unrelated health events make it more difficult to \nseparate vaccine- related effects from other causes. Dr. Meyer welcomed input from the \ncommittee on how to enhance long- term safety monitoring.  \nDr. Malone followed up by emphasizing that the pharmacokinetics of mRNA vaccines differ significantly from traditional vaccines. He noted that prolonged antigen presence in the body, up \nto 700 days according to a Yale study, is unprecedented in vaccinology . This extended \nexposure has been linked in animal models to immune system effects such as broad \nimmunoglobulin class switching, which are not currently captured by existing safety monitoring \nsystems. Dr. Malone suggested these changes could affect overall  immune function and \ninfluence vulnerability to other infectious diseases. He related this concern to Dr. Levi’s earlier \nquestion about vaccine effectiveness estimates. While acknowledging the rigor of the current \nsafety framework, he encouraged expanding safety analyses to consider the unique profile of \nmRNA vaccines, including the potential for delayed or immune- related effects. He \nrecommended broadening the scope of monitoring to include potential long- term immunologic \nrisks and benefits, which could hel p address public concerns and improve understanding of \nthese products.  \nDr. Meyer explained that since vaccination efforts began in December 2020, the CDC has maintained robust monitoring for several years. The current systems are designed to detect any \nadverse events, including those that may be cumulative over time or result  from multiple doses. \nIf there were any emerging safety concerns or effects on organ systems, the existing \nsurveillance infrastructure would be well -positioned to identify them.  \nDr. Thornburg noted that preclinical animal studies have shown spike protein detection up to nine days after injection, but not in the liver, and no detection beyond that time. In humans, \n21 \n limited data from an autopsy study of 20 individuals revealed that vaccine mRNA was detected \nonly in axillary nodes within 30 days post -vaccination, and not in the spleen or mediastinal \nlymph nodes. Protein was not detected in lymph nodes, the left ventric le, liver, or other organs, \nwith only nonspecific staining observed.  \nDr. Georgina Peacock (CDC/NCIRD) presented on COVID -19 vaccine coverage and \nimplementation. One of the primary data sources used by the Immunization Services Division at CDC to assess vaccine coverage, including COVID -19 vaccination, is the National Immuni zation \nSurvey (NIS). The NIS is a random -digit-dial cellular telephone survey of U.S. adults aged ≥18 \nyears across all states, 5 local jurisdictions, and U.S. -associated territories. For children, data is \nreported by a parent or guardian. All responses are self-reported. The survey collects data from \nabout 15,000 adults per week or around 60,000 adults per month. The data is weighted to represent the non -institutionalized U.S. population.  \nFrom September 2024 through April 2025, COVID -19 vaccination coverage for at least one \ndose reached 44% among adults aged 65 years and older and 23% among adults aged 18 \nyears and older.  \nCOVID -19 vaccination coverage among older adults increased between the 2023– 2024 and \n2024– 2025 seasons. For adults aged 65– 74, coverage increased by nearly 5 percentage points, \nwhile adults aged 75 years or older saw an increase of about 8 percentage point s by the end of \nthe 2024– 25 season.  \nAs of April 2025, approximately 5.6% of children under 4 years old were up to date with COVID -\n19 vaccination for the 2024– 2025 season. Among children aged 5– 17 years, about 16% had \nreceived at least one dose since August 2024. Overall, 13% of children aged 6 months to 17 \nyears were up to date with their COVID -19 vaccination for the 2024– 2025 season.  \nAmong immunocompromised adults who received their first 2024- 2025 COVID -19 vaccine dose \nin August or September 2024, 8% were fully vaccinated with two doses by the end of March \n2025. When stratified by age, full -vaccination coverage was 16.6% for adults aged 50– 64, 2.4% \nfor those aged 18– 49, and 0.8% for adults aged 65 years and older.  \nDr. Peacock summarized that COVID -19 vaccination coverage for older adults improved in the \n2024– 2025 season compared to the previous year. Coverage among adults aged 18 years and \nolder remained similar between seasons, and approximately 13% of children aged 6 months to 17 years were up to date with their COVID -19 vaccinations by the end of April 2025.  \nDr. Levi asked about vaccine uptake among healthcare professionals, as their vaccination behaviors can influence public trust and recommendations.  \nDr. Peacock responded that data on COVID -19 vaccination rates among healthcare \nprofessionals is not included in the specific dataset presented. However, the National Immunization Survey and other sources do collect this information. Dr. Peacock offered to bring \nrelevant data to a future ACIP meeting or share it with the work group, noting that it is not \ncurrently available for discussion.  \nDr. Meissner noted that COVID -19 vaccine uptake remains low, with less than 20% coverage \namong young children and even among high- risk adults over 75. He asked whether low public \nuptake influences the recommendations made by ACIP, specifically if low vacci nation rates \namong children affect whether ACIP continues to recommend the vaccine for that group.  \nDr. Peacock responded that this is a discussion for the committee to consider. She noted being \nencouraged by the increase in vaccination among adults over 65, especially those over 75. She \nsuggested that this may reflect healthcare providers recommending t he vaccine to patients with \n22 \n a higher risk of hospitalization or death. She added that the final recommendation ultimately \ncomes from the committee.  \nDr. Meissner expressed concern that if the CDC issues recommendations that the public does \nnot follow, it could erode confidence in those recommendations. He acknowledged that there \nmay not be an easy solution but emphasized the importance of considering public acceptance \nwhen developing guidance.  \nDr. Kulldorff emphasized that the committee must base its recommendations on evidence -\nbased medicine. However, he acknowledged that the low COVID -19 vaccination rates among \nchildren likely reflect a lack of trust among many parents in the recommendations i ssued by the \nACIP. He agreed that Dr. Meissner raised an important and timely concern.  \nDr. Daskalakis added that part of the evidence- to-recommendation framework used in the work \ngroup includes an assessment of both feasibility and acceptability. He clarified that these factors \nhave historically been part of all vaccine- related discussions and are built into the process that \ninforms committee discussions and ultimately leads to recommendations.  \nDr. Meissner asked whether there is a defined threshold at which continuing to make a \nrecommendation may no longer be beneficial, particularly if uptake remains persistently low.  \nDr. Daskalakis responded that this is precisely why the committee holds these discussions. As \nfeasibility, acceptability, and uptake are reviewed within the work group, that information is \nbrought to the committee for consideration. Based on this feedback,  the committee ultimately \nmakes recommendations, which can then be further reviewed.  \nDr. Pebsworth expressed concern about the low uptake of COVID -19 vaccines and the high \nvolume of reports submitted to VAERS compared to other vaccines. She noted that, as of her \nlast review, approximately 1.6 million reports had been submitted, and cited s tudies suggesting \nthat only about 10% of adverse events are typically reported, raising the possibility of \nunderreporting. Given these concerns, she emphasized the importance of transparency and \naccess to data not typically shared, including findings from preclinical animal studies, \nreproductive toxicity data, and biodistribution studies. She believes these data could help clarify \ncurrent uncertainties.  \nDr. Meyer addressed concerns about underreporting in VAERS by clarifying that studies often cited to support underreporting typically include mild events, such as sore arms or rashes, which \nare often not reported. She noted that CDC research has shown significantly higher reporting \nrates for serious adverse events. For example, VAERS captures up to 76% of anaphylaxis \ncases and up to 64% of Guillain- Barré Syndrome cases, depending on the vaccine. She added \nthat similar findings have been observed for intussusception after rotavirus vaccination and \nvaccine -associated polio. Dr. Meyer emphasized that the CDC is confident that a majority of \nserious adverse events are reported to VAERS.  \nDr. Levi acknowledged improvements in reporting but maintained that underreporting of adverse \nevents, particularly myocarditis, likely still exists across systems. He emphasized that \ncomparing rates from VAERS, clinical diagnoses, and studies measuring biomarkers, such as \ntroponin levels, before and after vaccination, reveals discrepancies. While the underreporting \nmay not be to the extent of 10%, it remains significant. He also noted that some serious adverse \nevents appear in VAERS at rates exceeding those seen with other vaccines, even after \nadjusting for the number of doses administered, which may indicate a signal that warrants \nfurther investigation.  \nDr. Adam MacNeil (CDC/NCIRD) concluded the COVID- 19 session with a partial presentation \non evidence- to-recommendations (EtR). The EtR framework outlines key domains used to guide \n23 \n decision- making, including public health problem, benefits and harms, values, acceptability, \nfeasibility, resource use, and equity. Each domain is linked to specific guiding questions. The \nfirst two domains, public health problem and benefits and harms, were reviewed and discussed \nby the workgroup. The remaining domains and final polling were scheduled for the final \nworkgroup call.  \nThe work group has consistently reviewed data related to the public health problem and benefits \nand harms domains of the EtR framework. Most recently, summaries of these domains were \ndiscussed during the May 29 and June 5 work group calls. These domains are largely informed \nby the epidemiology, vaccine effectiveness, and safety data previously presented, and were \nreflected in the June 12 ACIP meeting presentations. The work group had planned to review the \nremaining EtR domains and complete final polling before the ACIP meeting. However, because the scheduled work group call did not take place, the EtR was not finalized, and final polling was \nnot conducted.  \nDr. MacNeil summarized the work group’s considerations on the public health problem, noting that while the burden from COVID -19 has declined year over year since 2021, substantial illness \nand death continue. Hospitalization and death rates remain highest among adults 65 years and older and infants six months and younger. Children under two years have the highest illness \nand death rates among pediatric groups, though deaths can occur at any age. Maternal vaccination remains the best protection for pregnant women and infants under six months who \nare not eligible for vaccination.  \nFor the benefits and harms domain, the work group concluded that the 2024– 2025 COVID -19 \nvaccination provides clear benefits in reducing hospitalizations and severe disease, particularly \nin adults. The vaccine has demonstrated consistent effectiveness across age groups based on prior formulations. Safety surveillance has identified myocarditis and pericarditis following \nmRNA vaccination, but no other serious risks have been confirmed beyond typical vaccine-\nrelated reactions. The work group also recognized that pregnant individuals face higher risks \nfrom COVID -19, and maternal vaccination offers protection to infants under six months, who are \nnot yet eligible for vaccination.  \nDr. Kulldorff thanked the presenters for their informative updates and acknowledged the thoughtful discussion that followed. He noted that no vote was scheduled on the topic and that \nthe committee looks forward to receiving the working group's report befor e the next meeting. He \nexpressed appreciation for both the CDC presenters and the many contributors behind the scenes.  \n \nAGENCY  UPDATES  \n \nThe C\nenters for Disease Control and Prevention (CDC)  \nDr. Demetre Daskalakis from the National Center for Immunization and Respiratory Diseases \n(NCIRD) provided an update on current domestic outbreaks. He reported that as of the meeting date, the CDC has identified 1,227 measles cases across 37 U.S. jurisdictions in 2025, with 23 outbreaks accounting for 89% of cases. A significant portion of these cases is linked to a large outbreak in the Southwest, with Texas reporting 750 cases across 35 counties and New Mexico \nreporting 81 cases. There are signs that the outbreak is plateauing, with a decline in new cases \nin the Southwest. However, the CDC continues to monitor for global introductions of measles into the U.S., though recent cases have resulted mainly in short, self -limiting transmission \nchains. The overall  risk to the U.S. population remains low; however, continued vigilance is \n24 \n necessary, particularly in under -immunized populations. Dr. Daskalakis also provided an update \non H5N1 (Avian influenza). Historically associated with birds and poultry, H5N1 was detected in \ncattle in 2024, resulting in over 1,000 affected herds. There have been 70 human cases, primarily among individuals with direct contact with animals. Recent data show a decrease in infections among both non- human mammals and birds, with no new human cases reported in \nover 15 weeks. He credited the USDA’s early detection efforts, including bulk milk testing, for \nthis progress. Dr. Daskalakis concluded by noting that the CDC remains focused on seasonal respiratory virus preparedness, including COVID -19, influenza, and RSV, to ensure Americans \nhave the tools to prevent these infections.  \nDr. Chris Braden, Principal Deputy Director of the National Center for Emerging and Zoonotic Infectious Diseases (NCEZID) provided additional updates on outbreak investigations. NCEZID is currently monitoring several foodborne outbreaks, including Salmonella linked to pistachio cream and eggs, which were detected through the PulseNet system. This system utilizes whole-genome sequencing to identify related cases. Dr. Braden also highlighted a cluster of systemic illnesses in Massachusetts linked to unauthorized Botox injections by an unlicensed provider. The CDC is supporting this investigation by supplying botulinum antitoxin, which is stored at CDC quarantine stations nationwide. Additionally, Dr. Braden noted emerging concerns regarding the New World screwworm, an animal parasite making its way from Central America into Mexico. Although primarily an animal health issue, human cases can occur, resulting in \nsevere myiasis (infestation of live tissue). CDC is collaborating with the USDA to monitor this situati on, as it poses risks to animal agriculture and, to a lesser extent, human health. \nFood and Drug Administration (FDA)  \nDr. Tracy Beth Hoeg from the FDA provided several updates. She began by addressing a recent \nFDA announcement regarding a safety label change for mRNA COVID -19 vaccines to reflect the \nongoing risk of myocarditis, particularly in males ages 12 to 24. FDA data from 2023 and 2024 identified a myocarditis rate of 27 cases per million in this group. She clarified that this differs \nfrom the CDC’s reported rate of 2 cases per million, as the FDA’s data are more stratified \nexplicitly by age and sex. Additionally, FDA data showed instances of late gadolinium enhancement on MRI six months post -vaccination, suggesting potential myocardial damage of \nuncertain clinical significance. Based on these findings, the FDA implemented the safety label \nchange.  \nDr. Hoeg also noted that the FDA’s Vaccines and Related Biological Products Advisory \nCommittee (VRBPAC) recommended the JN.1 variant antigen for the 2025 to 2026 COVID -19 \nvaccine, consistent with the previous year, due to slower viral mutation rates. The FDA has approved two updated vaccines, Numovoxid and MN.X Spike, both with narrowed indications for individuals ages 12 to 64 with at least one risk factor for severe COVID -19, and for adults 65 \nand older. Both manufacturers have committed to post -marketing randomized controlled trials to \nevaluate vaccine efficacy, particularly in adults ages 50 to 64. \nDr. Hoeg also referenced a recent FDA decision to pause use of the live chikungunya vaccine in \nadults 60 and older due to reports of 17 adverse events, including two deaths. She concluded by highlighting a study by Albertson et al., published in Infectious Diseases and Therapy , that \n25 \n addresses subclinical myocarditis post -vaccination in individuals ages 5 to 30. This study fulfills \npart of a post -marketing requirement and provides additional data on this safety concern.  \nIndian Health Services (HIS)  \nDr. Matthew Clark from IHS provided an update on vaccination efforts in tribal communities. He \nemphasized that IHS is working closely with federal, tribal, and urban Indian organization partners to mitigate the risk of vaccine -preventable illnesses among v ulnerable populations. In \nalignment with its mission, IHS is committed to raising health status and improving health outcomes in American Indian and Alaska Native communities through a comprehensive approach. This includes promoting healthy lifestyles, supporting traditional culture and healing, providing preventive screenings, and managing both acute and chronic diseases. As a health care system serving 2.1 million American Indian and Alaska Native beneficiaries, vaccination remains a key component of IHS’s strategy. The agency advances this work through proactive education, informed consent, and respect for the values of patients, their families, and the \ncommunities they serve. Dr. Clark noted that tribal communities face unique challenges that \nimpact access to preventive care, and IHS is actively collaborating with tribal health partners to identify vaccine priorities and establish best practices that meet the specific needs of Indian \nCountry.  \nRSV  VACCINES -MATERNAL/PEDIATRIC \n \nD\nr. Adam MacNeil (CDC/NCIRD) introduced the Maternal/Pediatric RSV Vaccine Work Group. \nRSV is the leading cause of hospitalization in U.S. infants, with most infected in their first year \nand nearly all by age two. About 2 to 3% of young infants are hospitalized, and 80% of those have no underlying conditions. All young infants are at risk for severe RSV. Before 2023, no \nlong- acting preventive products were available.  \nIn 2023, two products to prevent severe RSV in infants were approved by the FDA and \nrecommended by the CDC and the ACIP. All infants should be protected through either maternal RSV vaccination or a long- acting monoclonal antibody. Pregnant women should receive one \ndose of the maternal RSV vaccine between 32 and 36 weeks of pregnancy. Nirsevimab is recommended for infants younger than 8 months entering their first RSV season and for some \nchildren aged 8 to 19 months at increased risk entering their second season.  \nA new long- acting monoclonal antibody, clesrovimab, is a third option to protect infants from \nsevere RSV disease. Clesrovimab was approved by the FDA on June 9, 2025, for use in infants born during or entering their first RSV season.  \nThe work group and ACIP have been reviewing data on clesrovimab since September 2024. In \nSeptember, the work group reviewed safety and efficacy data from Merck. In October, ACIP reviewed these data along with the work group’s interpretation. From November 2024 through April 2025, the work group reviewed the GRADE assessment and the EtR framework for \nclesrovimab.  \n26 \n Since the April 2025 ACIP meeting, the work group has reviewed data on the uptake, safety, and \neffectiveness of the maternal RSV vaccine and the long- acting monoclonal antibody from the \n2024– 2025 season.  \nDr. MacNeil shared that the session would include updates on current RSV prevention products, \nincluding uptake, effectiveness , and impact, and safety data for the maternal RSV vaccine and \nlong- acting monoclonal antibody. The session would also cover the evidence- to-\nrecommendation framework for clesrovimab, the work group’s interpretations, and clinical \nconsiderations for clesrovi mab.  \nDr. Georgina Peacock (CDC/NCIRD) presented on the implementation and uptake of \nNirsevimab and maternal vaccination for infant protection from RSV. Data sources include the \nNational Immunization Survey, a random -digit-dial cellular phone survey of U.S. adul ts aged 18 \nand older across jurisdictions and territories; Immunization Information Systems (IIS), which are \nconfidential, population- based databases that record immunizations administered by \nparticipating providers. CDC funds 64 jurisdictions to operate I IS, which provide monthly \naggregate data for COVID -19, influenza, and RSV, as well as quarterly de -identified line- level \ndata. The Vaccine Safety Datalink (VSD) provides vaccination coverage estimates based on \nelectronic health records, including maternal RSV vaccination coverage.  \nImmunization Information Systems data show monthly administration of nirsevimab to infants \nunder eight months of age during the 2024– 2025 RSV season. More infants received protection \nthrough nirsevimab in the second season than in the first season, 2023– 2024. \nInfants born during the 2023– 2024 RSV season (October to March) typically received \nnirsevimab closer to birth, while those born before September received it more than one month after birth. This pattern aligns with the availability and recommendations for nirsevimab, which \ntypically begin shortly before the RSV season in most states.  \nDuring the second season of implementation, more infants born during the RSV season \nreceived nirsevimab within the first month of life compared to the 2023– 2024 season. This \nsuggests an improved understanding of administration guidance among healthcare providers \nand better access to nirsevimab.  \nFrom September 2024 through January 2025, 38.5% of pregnant women ages 18 to 49 \nreceived the RSV vaccine. Coverage varied by race and ethnicity, ranging from 25.7% among Black pregnant women to 52.6% among Asian pregnant women. These patterns are consisten t \nwith other vaccines during pregnancy, which typically show higher coverage among Asian and White non -Hispanic women and lower coverage among Black non- Hispanic and Hispanic/Latino \nwomen. Fifty -seven percent of infants born between April 2024 and March 2025 were protected \nagainst RSV through either maternal vaccination or receipt of nirsevimab.  \nFor infants who become eligible, nirsevimab is recommended within the first week of life for those born between October and March in most of the continental United States. Birthing \nhospitals play a vital role in ensuring timely administration, especially f or infants without \ncommercial insurance. Approximately 45% of U.S. children ages 0 to 17 lack commercial \ninsurance and are less likely to be seen by a primary care provider within one week of birth. \n27 \n Providing nirsevimab in the hospital helps prevent missed opportunities for RSV immunization \nand supports coordination of care with pediatricians.  \nParticipation in the Vaccines for Children (VFC) program by birthing hospitals promotes access \nto all ACIP -recommended vaccines. It allows newborns to receive necessary immunizations, \nsuch as nirsevimab and hepatitis B, before hospital discharge without up front costs to the \nhospital for VFC -eligible children. This supports equitable, high- quality care for all infants at risk \nfor RSV, regardless of insurance status.  \nIn 2023, only 10% of U.S. birthing hospitals were enrolled in the VFC program when nirsevimab was added to the routine schedule. Through updated policies, new partnerships, and strong \noutreach, enrollment has grown to over 1,000 hospitals in under two year s. \nFor the 2025– 2026 RSV season, the supply of monoclonal antibodies is expected to meet \ndemand and arrive earlier than in the previous season, supporting broad availability and a \nsmooth program rollout. CDC is working with state partners, professional organi zations, and the \nIndian Health Service to improve access and uptake of both maternal vaccines and infant monoclonal antibodies. Preseason technical assistance is underway to support ordering and logistics. Increased availability of 50 mg doses of nirsevimab is expected early in the season, \nand the newly licensed clesrovimab will be available once added to the CDC’s VFC contracts.  \nDr. Peacock summarized that during the 2024– 2025 season, more infants born during the RSV \nseason received nirsevimab within their first month of life compared to the previous year. This \nimprovement was likely due to greater awareness among healthcare provi ders and families, as \nwell as better supply availability. Maternal vaccination and RSV monoclonal antibodies \nprotected 57% of infants born between April 2024 and March 2025, demonstrating the value of offering both options. Increased enrollment of birthing hospitals and improved early supply \nshould enhance access to RSV protection in the upcoming season.  \nDr. Adam MacNeil (CDC/NCIRD) presented the effectiveness and impact of RSV prevention products in infants during the 2024– 2025 season. The CDC utilized data from three primary \nnetworks to evaluate RSV product effectiveness (PE) in the U.S., all based on va riations of the \ncase -control design. Two networks, VISION and NVSN, used a test -negative design, where \ninfants with acute respiratory illness who received medical care (emergency department visit, hospitalization, or ICU admission) and were tested for RSV.  Those who tested positive (cases) \nwere compared to those who tested negative (controls) in terms of their RSV immunization status. The third, the Overcoming COVID -19 Network, used a matched case- control design \ncomparing RSV -positive children with ICU admi ssions with matched RSV -negative controls. In \nall three networks, effectiveness was estimated by comparing the odds of RSV immunization \nbetween RSV -positive and RSV -negative infants. Each network has unique strengths: VISION \nuses electronic health records from emergency departments and hospitals in six states, NVSN \nconducts active surveillance in seven pediatric academic centers, and the Overcoming Network \ncollects data from 26 pediatric intensive care units across 23 states.  \nEach network verified immunization status through electronic health records and immunization \nregistries; NVSN and the Overcoming Network also included provider records and parental \nreports. VISION and NVSN analyzed data from October 2024 to March 2025, whi le Overcoming \n28 \n analyzed data from December 2024 to April 2025. In all platforms, cases were children who \nhave tested positive for RSV. NVSN systematically tested all enrolled children, including those \nwho have not undergone clinical testing. Controls were children who tested negative for RSV; in \nNVSN, this may have included children without clinical testing. The Overcoming Network \nenrolled matched controls based on site, age, and date of hospitalization of cases.  \nAll three studies included infants who were <8 months old on October 1, 2024, or born after that \ndate during the study period. For maternal RSV product effectiveness, VISION included infants \nborn on or after September 14, 2024, which is 14 days after vacci ne availability in most of the \nU.S., while NVSN included infants under 6 months of age during the study period. All analyses \nused multivariable logistic regression, adjusting for site, age in months, and enrollment timing. \nVISION analyses also adjusted for  race, ethnicity, and sex. For nirsevimab effectiveness, NVSN \nand Overcoming analyses also adjusted for presence of at least one high- risk medical condition. \nOvercoming analyses additionally adjusted for the Social Vulnerability Index, and NVSN also \naccounted for race and ethnicity and insurance status in the maternal vaccine analysis.  \nNirsevimab showed strong effectiveness against RSV -associated emergency department visits \nduring infants’ first RSV season. In the VISION analysis of over 4,000 ED visits, 79% of RSV -\npositive children did not receive nirsevimab, compared to 64% of RSV -negative children. In the \nNVSN analysis of nearly 500 ED visits, 86% of RSV -positive children did not receive nirsevimab, \ncompared to 56% of RSV -negative children. Among immunized children, the median time since \nthe last dose was 68 days. The adjusted product effectiveness against RSV -associated ED \nvisits was 63% in VISION and 76% in NVSN, with overlapping 95% confidence intervals, \nindicating consistent protection across both networks.  \nIn the VISION analysis of over 600 hospitalizations, 81% of RSV -positive children did not \nreceive nirsevimab, compared to 55% of RSV -negative children. In the NVSN analysis of nearly \n700 hospitalizations, 89% of RSV -positive children had not received nirsevimab, compared to \n61% of RSV -negative children. Among those who had received the antibody, the median time \nsince dose was 61 days in VISION and 52 days in NVSN. The adjusted effectiveness against \nRSV-associated hospitalization was 79% in VISION and 82% in NVSN, with overlapping 95% \nconfidence intervals.  \nIn the VISION analysis of 374 ICU admissions, 86% of RSV -positive infants had not received \nnirsevimab, compared to 55% of RSV -negative infants. In NVSN, 92% of RSV -positive infants \ndid not receive the antibody, compared to 56% of RSV -negative infants. The Overcoming \nplatform showed similar results, with 87% of RSV -positive infants having not received \nnirsevimab versus 56% of RSV -negative infants. Among those who had received nirsevimab, \nthe median time since dose at ICU admission was 56 days in VISION, 52 d ays in NVSN, and 50 \ndays in Overcoming. Adjusted product effectiveness against RSV -associated ICU admission \nwas estimated at 82% for VISION, 88% for NVSN, and 88% for Overcoming, with overlapping \n95% confidence intervals across all three platforms.  \nDuring the 2024– 2025 RSV season in the United States, the effectiveness of the maternal RSV \nvaccine against RSV -associated emergency department (ED) visits in infants during their first \nseason was assessed using data from the VISION platform. Among nearly 1,000 ED visits, 79% \n29 \n of RSV -positive infants did not have evidence of maternal RSV vaccination, compared to 65% of \nRSV-negative infants. Among infants whose mothers had received the vaccine, the median \nnumber of days since birth was 53, and the median number of days since maternal vaccination \nwas 85. The estimated vaccine effectiveness against RSV -associated ED visits was 54%, with a \n95% confidence interval of 35% to 67%.  \nDuring the 2024– 2025 RSV season, maternal RSV vaccine effectiveness against infant \nhospitalization was 79% in the VISION network and 70% in NVSN, with overlapping confidence \nintervals. In both networks, over 80% of RSV -positive infants had no documented maternal \nvaccination. Among vaccinated groups, the median time since birth was around one month, and \nthe median time since maternal vaccination was just over 70 days.  \nWhen interpreting these real -world product effectiveness findings, it's important to consider that \ndifferences in enrollment and population across systems may limit comparability. While study \ndesign and analysis help control confounders such as health -seek ing behavior, residual \nconfounding is still possible, although a variety of sensitivity analyses were performed to assess \nthe influence of known confounders. There is also a risk of misclassifying RSV immunization \nstatus, although multiple data sources wer e used to verify immunization records.  \nRSV product effectiveness estimates align with clinical trial efficacy data for both nirsevimab and \nmaternal RSV vaccination, particularly in terms of hospitalization and ICU admissions. Although \nED visits were not measured in clinical trials, the real -world data suggest both products are \neffective in preventing RSV -associated emergency visits, hospitalizations, and severe illness. \nOngoing monitoring will be important to evaluate additional outcomes.  \nTo assess the impact of RSV prevention products on pediatric RSV -associated hospitalizations \nin the U.S., data were analyzed from two active, population- based surveillance systems. RSV -\nNET, part of the RESP- NET system, monitors RSV, influenza, and COVID -19 hospitalizations \nacross all ages in 13 states. The second system, NVSN, tracks hospitalizations among children \nwith acute respiratory illnesses across seven U.S. pediatric medical centers.  \nAn ecological analysis was conducted to assess changes in pediatric RSV -associated \nhospitalization rates before and after the introduction of RSV prevention products. RSV \nhospitalization rates from pre -pandemic seasons (2018– 2020 for RSV -Net, 2017– 2020 for  \nNVSN) were compared to rates from the 2024– 2025 season, the second year of product \navailability. Seasons from 2020– 2023 and 2023– 2024 were excluded due to pandemic \ndisruptions and limited product uptake, respectively. Weekly and monthly hospitalization ra tes \nwere analyzed, and cumulative rates were compared across seasons. Rate ratios and relative \nrate reductions were calculated to assess the impact of RSV prevention products. Analyses \nfocused on three age groups with different RSV prevention options: infants 0 –7 months (eligible \nfor maternal vaccine or nirsevimab), children 8– 19 months (limited eligibility for nirsevimab \nbased on risk conditions), and children 20– 59 months (not eligible for RSV prevention products, \nused as a comparison group).  \nDuring the 2024– 2025 RSV season, prevention products were available before the season \nbegan in most states, with coverage increasing over time. By March 2025, nirsevimab coverage \n30 \n among infants aged 0– 7 months ranged from 21% to 48% across reporting jurisdictions. As of \nJanuary 2025, 39% of pregnant women aged 18– 49 had received the RSV vaccine.  \nThe ecological analysis compared RSV hospitalization rates among infants (0 to 7 months), \ntoddlers (8 to 19 months), and preschoolers (20 to 59 months) before and after the introduction \nof RSV prevention products. Historically, infants have experienced the  highest hospitalization \nrates, followed by toddlers and preschoolers, with rates remaining relatively consistent  within \neach age group. During the 2024– 2025 season, new RSV prevention products became \navailable for infants and some high -risk toddlers, whil e preschoolers remained ineligible for \nthese products. By comparing changes in hospitalization rates within each age group, the \nanalysis assessed whether the declines among infants eligible for prevention were greater than \ndeclines in the other two age groups, which would suggest a population- level impact of the new \nproducts.  \nResults from the analysis showed that the two networks identified over 20,000 RSV -associated \nhospitalizations in children under five across the compared periods. In the 2024– 2025 season, \nthe proportion of children aged <5 years with an RSV -associated hospi talization who were aged \n0 to 7 months decreased from 51% to 29% in RSV -NET and from 46% to 38% in NVSN in 2024 -\n2025 compared to prior seasons before the introduction of prevention products. The median age at hospitalization also nearly doubled, from 7.7 t o 15.4 months in RSV -NET and from 6.3 to 12.7 \nmonths in NVSN. This indicated that children hospitalized with RSV during the 2024– 2025 \nseason were typically older than in prior seasons.  \nCumulative adjusted RSV -associated hospitalization rates in the 2024– 2025 season were \ncompared to those in prior seasons before product introduction across three age groups. Among infants aged 0 to 7 months, rates dropped from 17 to 10.5 per 1,000 in RSV -NET and from 16 to \n11 per 1,000 in NVSN, corresponding to a 38% and 31% reduction in hospitalization rates, respectively. No reductions occurred among children aged 8 to 19 months or 20 to 59 months, suggesting the observed decline was limited to the age gr oup eligible for RSV prevention \nproducts.  \nAmong infants aged 0 to 7 months, further analysis showed that RSV -associated hospitalization \nrates were reduced by nearly half among those aged 0 to 2 months. In the 2024– 2025 season, \nrates among infants aged 0 to 2 months dropped by 47% in RSV -NET and 46% in NVSN \ncompared to prior seasons.  \nDr. MacNeil concluded that two population- based surveillance networks demonstrated \nsignificant reductions in RSV -associated hospitalizations during the 2024– 2025 season among \ninfants eligible for preventive products, with decreases of 38% and 31% among those aged 0 to \n7 months compared to prior seasons before product introduction. The greatest reductions were \nobserved in infants aged 0 to 2 months, the group at the highest risk for hospitalization, \nhighlighting the importance of timely protection through maternal vaccination during pregnancy \nor the administration of nirsevimab in the first week of life. Ongoing monitoring of RSV disease \ntrends, including severity and age distribution, remains crucial for evaluating the long- term \nimpact.  \n31 \n Dr. Levi emphasized the need for more detailed analyses to better understand the impact of \nRSV prevention products. He suggested evaluating whether certain groups, such as preterm \ninfants or those with comorbidities, benefit more than healthy, full -term in fants. He also \nrecommended assessing broader outcomes, such as all -cause lower respiratory tract infections \nand overall respiratory infections, to ensure that reductions are not due to changes in testing \npractices. Additionally, he proposed examining hospi talization severity, including length of stay \nand type of care provided, to capture the overall clinical benefit better.  \nDr. MacNeil acknowledged the importance of reducing all respiratory infections, not just RSV, and emphasized that preventing infant and pediatric hospitalizations is highly valuable. RSV \nalone accounts for a large portion of hospitalizations in newborns, s o RSV prevention products \nare already having a meaningful public health impact. Regarding more granular analyses, such \nas subgroup evaluations, it was noted that these would be useful. Still, limitations in statistical \npower may affect the ability to explore them in greater depth.  \nDr. Hibbeln noted that combining small -sample clinical trials with large -scale ecological studies \ncan be a challenging task. Still, it appears that both types of studies show similar effect sizes for RSV prevention products. He asked for confirmation on whether that observation is accurate.  \nDr. MacNeil confirmed that although the clinical trials were not conducted in the United States, \nand some differences exist, the overall magnitude of effect appears consistent. The observed \nreal-world impact aligns with expectations based on the clinical t rial results.  \nDr. Hibbeln noted that the major event between the two ecological studies was the COVID -19 \npandemic and asked whether there is any evidence of an interaction or a potential protective effect of COVID -19 vaccination on RSV hospitalizations or related outcom es. \nDr. MacNeil responded that, biologically, there would not be a direct effect of COVID -19 or \nCOVID -19 vaccination on RSV, as the two viruses are very different and unrelated in their \nmechanisms of infection.  \nDr. Malone noted that monoclonal antibodies are particularly vulnerable to viral drift and suggested that it could be beneficial if the two available monoclonals target different epitopes. \nHe asked whether there is information available on whether these tw o monoclonals are directed \nat distinct regions of the virus.  \nDr. MacNeil explained that both monoclonal antibodies target the larger prefusion protein. \nHowever, there is a possibility that if resistance develops against one, the other could still offer \nprotection. This consideration was part of the work group's rati onale and deliberation in \nrecommending the inclusion of a second monoclonal antibody.  \nDr. Malone expressed support for the approach and noted that the discussion highlights the significant viral and infectious pressure currently present. He asked whether there is active \nmonitoring in place to track changes that could impact the effectivenes s of monoclonal \nantibodies due to viral drift.  \nDr. MacNeil explained that RSV infects individuals multiple times throughout their lives, resulting \nin the continuous circulation of the virus. Because of this, protecting a relatively small population \n32 \n is not expected to create significant population- level selective pressure. He added that while \nsome genomic monitoring of RSV is conducted, widespread ecological selective pressure is not \nanticipated, since the virus continues to be transmitted broadly among the general population.  \nDr. Malone noted that drug- drug interactions will be an important issue for ACIP to consider \nmoving forward. He pointed out that among those receiving monoclonal antibody products, \nsome infants are likely fully vaccinated under the standard birth schedule,  while others may not \nbe. If that is the case, he suggested it would be valuable to collect and analyze data comparing \nsafety and effectiveness between these groups. He emphasized that demonstrating no \ndifference in outcomes between those who receive standard vaccinations concurrently and \nthose who do not would be useful if such monitoring is not already in place.  \nAn SME clarified that the two monoclonal antibodies bind to different locations on the virus. \nWhile some viruses are known to drift away from the effectiveness of monoclonal antibodies, \nthese monoclonals are likely less prone to such drift due to the virus 's evolutionary \ncharacteristics. However, genetic surveillance is ongoing to monitor changes and ensure \ncontinued effectiveness.  \nDr. Levi emphasized the importance of monitoring how vaccine efficacy changes over time, even within a single season. Referring to the maternal RSV vaccine data, he noted that between \ndays 180 and 360, a signal appeared suggesting negative efficacy, with m ore hospitalizations \noccurring among vaccinated individuals compared to those who were not vaccinated. He \nacknowledged that RSV is a challenging virus that often responds unpredictably to interventions \nand stressed the need for careful interpretation and a deeper understanding of potential \nexplanations for these findings.  \nDr. MacNeil acknowledged that the effectiveness of RSV prevention products wanes over time. He emphasized that the goal is to protect infants during their most vulnerable period, particularly \nin the first two months of life, before their immune systems are fully developed. By providing \nprotection early, the aim is to help children reach an age where, like healthy teenagers or adults, \nthey may still get infected with RSV but are far less likely to develop severe disease. The \nprimary objective is to reduce the risk of serious outcomes during the earliest and highest -risk \nstage of life.  \nDr. Picaro addressed the question about monitoring protection beyond 150 days, explaining that the current challenge stems from the way these products are administered, typically at the \nbeginning of the RSV season. As coverage increases over time, the number of children who have reached 120 to 180 days post -immunization during the observation period decreases. This \nlimits the ability to assess long -term protection in current analyses. He noted that this challenge \nis tied to the seasonal nature of product rollout. However, he expressed hope that data from regions where RSV circulates more consistently throughout the year may help answer questions \nabout the duration of protection.  \nDr. Malini DeSilva (HealthPartners) shared updates on prenatal RSVpreF vaccine safety. \nEstablished in 1990, the Vaccine Safety Datalink (VSD) is a collaborative project between CDC's Immunization Safety Office and integrated healthcare organizations in the  United States. \nThe VSD primarily monitors vaccine safety through observational, multi -site studies that utilize \n33 \n real-world data. It includes data on approximately 15.5 million individuals annually, representing \nabout 4.5% of the U.S. population, with an annual birth cohort of roughly 115,000 live births. \nData are organized using a common data model with standardized coding systems. Currently, \n13 VSD sites provide clinical, methodological, and data expertise, with 11 of those sites \ncontributing data.  \nThe prenatal RSV vaccine was recommended for use by the ACIP in September 2023 for \nadministration between 32 and 36 weeks of gestation, with seasonal use from September \nthrough January. In the phase 3 RSVpreF clinical trial, non -significant imbalances were \nobserved among vaccinated women compared to placebo recipients in rates of preterm birth, \ngestational hypertension, and preeclampsia.  \nPrenatal RSVpreF vaccine safety outcomes evaluated in this study included acute outcomes \noccurring within 42 days of vaccination. These outcomes were preterm birth, small for \ngestational age at birth, stillbirth, and hypertensive disorders of pregnancy. Hy pertensive \ndisorders were assessed both as a combined outcome and as individual conditions, including \ngestational hypertension, preeclampsia, eclampsia, and HELLP syndrome.  \nA target trial emulation design was used to compare RSVpreF -vaccinated and unvaccinated \npregnant women at each gestational week, aiming to mimic a randomized trial using \nobservational data. The study included pregnant women aged 16– 49 years with a gestational \nage of 32 to less than 37 weeks between September 22, 2023, and January 31, 2024 (or \nFebruary 29, 2024, for two sites). Vaccinated individuals were matched one- to-one with \nunvaccinated individuals by site and likelihood of vaccination, based on the sam e gestational \nweek. Outcomes were tracked from the index date through two weeks after pregnancy ended. Unvaccinated matches were assigned the same index date as their vaccinated counterpart, and \npairs were censored if the unvaccinated individual later received the vaccine.  \nRisk ratios with 95% confidence intervals were estimated using a log- binomial model with robust \nvariance, adjusting for nulliparity. For small -for-gestational -age infants at birth, matched sets \nwere excluded if infant weight was missing for either infant. For hypertensive disorders of \npregnancy, matched sets were excluded if disease onset occurred on or before the index date \nfor either pregnant woman.  \nThe analysis included 13,966 matched pairs; however, the cohort does not represent unique \nindividuals, as some initially unvaccinated participants were later vaccinated and subsequently \nrematched. While overall characteristics were similar, RSV -vaccinated women were generally \nolder than their unvaccinated matches. The vaccinated group had a higher proportion of Asian \npatients and a lower proportion of Black and Hispanic patients. Additionally, 98.5% of the \nvaccinated group had received at least one other vaccine during pregnancy, compared to 81% \nin the unvaccinated group. A higher percentage of nulliparous women was also observed in the \nvaccinated group.  \nThe analysis found no significant differences in the risk of acute safety outcomes between \nRSVpreF -vaccinated pregnant women and their unvaccinated matches across all evaluated \ntime intervals (1 –6 days, 1– 21 days, and 1– 42 days).  \n34 \n The analysis found no association between RSVpreF vaccination during pregnancy and the risk \nof preterm birth, small for gestational age at birth, or stillbirth. However, there was a statistically \nsignificant association between RSVpreF vaccination and hypertensive disorders of pregnancy. \nThe adjusted risk ratio for any hypertensive disorder was 1.09, with significant associations \nobserved for both preeclampsia and gestational hypertension.  \nAmong individuals with diagnosed hypertensive disorders of pregnancy, rates of cesarean \ndelivery and post -birth hospitalization admissions were similar between RSVpreF- vaccinated \nand unvaccinated groups. Lengths of stay over 3 days were slightly higher in the vaccinated \ngroup, except for infants delivered by cesarean. Overall, the findings suggest comparable \nseverity of hypertensive disorders of pregnancy between the two groups.  \nIn the phase 3 clinical trial of the RSVpreF vaccine administered during pregnancy, there were \nmore cases of gestational hypertension and preeclampsia among vaccine recipients compared \nto placebo recipients. However, these differences were not statisticall y significant.  \nA retrospective observational cohort study of patients who delivered at 32 weeks and 0 days \ngestation or later at two New York City hospitals between September 22, 2023, and January 31, 2024, found a significant association between RSVpreF vaccination and hypertensive disorders \nof pregnancy using a time- dependent Cox regression model. However, this association was not \nsignificant in either unadjusted or adjusted multivariable logistic regression models. In stratified \nanalyses by site and insurance status, t he association persisted only among patients with \nprivate insurance and at one of the two hospitals.  \nDr. DeSilva concluded that the RSVpreF vaccine is not associated with increased risk for acute safety outcomes, preterm birth, small for gestational age at birth, or stillbirth. However, the vaccine is associated with a small but statistically significant increased risk for hypertensive \ndisorders of pregnancy. These findings are consistent with results from the Phase 3 clinical trial \nand a large observational study; however, the association may be influenced by residual \nconfounding or outcome misclassificat ion. Importantly, the severity of hypertensive disorders \nappeared similar between vaccinated and unvaccinated individuals based on rates of cesarean \ndelivery, post -birth hospital admissions, and length of stay. Results from the 2024– 2025 season \nare pending and will provide additional insight into the safety of the prenatal RSV vaccine.  \nDr. Matthew Daley (Kaiser Permanente Colorado) presented on monitoring the safety of nirsevimab in infants born through <8 months. Nirsevimab is a long- acting monoclonal antibody \nrecommended for the prevention of RSV disease in infants. It is intended for infants from birth to \nunder 8 months of age who have not received the RSV vaccine during pregnancy, as well as for \nselect high- risk infants aged 8 to 19 months. Phase 3 clinical trials demonstrated high efficacy, \nand post -licensure data showed strong effec tiveness. Although there was a severe shortage \nduring the 2023– 2024 season, uptake remained high within the VFC and VSD populations. A \ntotal of 72 percent received either nirsevimab or the maternal RSV vaccine.  \nThe safety profile of nirsevimab is based on three randomized clinical trials, which included both \nhealthy and high- risk infants. Across these trials, 3,184 infants received nirsevimab, 1,284 \nreceived a placebo (with a 2- to-1 randomization), and 304 receiv ed palivizumab, another \nmonoclonal antibody targeting RSV. Adverse events were generally balanced between the \n35 \n nirsevimab and comparator groups. Seven infants who received nirsevimab experienced \nrashes, primarily papular or maculopapular in nature. Importantly, no cases of anaphylaxis, \nserious hypersensitivity reactions, or immune complex diseases were reported.  \nAlthough clinical trials provided important safety data, additional post -licensure monitoring is \nneeded to assess rare adverse events and evaluate safety when nirsevimab is administered \nduring routine care in the general population. The objective of this study was to examine the safety of  nirsevimab by analyzing prespecified adverse events among recipients in the Vaccine \nSafety Datalink (VSD). While nirsevimab is a passive immunization, the CDC and ACIP \nspecifically requested that the VSD evaluate its safety.  \nThe VSD is an observational system that utilizes EHR data from a birth cohort of approximately \n115,000 individuals annually. It integrates data from electronic health records, claims, immunization registries, and diagnosis codes across inpatient, emergency , and outpatient \nsettings. A key strength of VSD is its ability to conduct rapid manual medical record reviews to \nvalidate diagnoses and ensure accuracy. It also uses advanced analytic methods, including self -\ncontrolled designs, to address confounding.  \nDuring the 2023– 2024 season, 36,719 infants received nirsevimab in the VSD. Prespecified \nadverse events were monitored using a self -controlled risk interval analysis, with results \nstratified by age group. No increased risk was identified for seizures, ITP,  drug reactions, fever, \nor sepsis. No cases of anaphylaxis were reported. Some non -anaphylactic allergic reactions, \nprimarily hives, occurred on the same day as administration. This finding is consistent with \nthose from the clinical trials.  \nFor the 2024– 2025 season, this analysis included all VSD -contributing sites and focused on \ninfants from birth to under 8 months of age who received nirsevimab between October 1, 2024, \nand February 1, 2025. All exposed infants were included, regardless of w hether they received \nvaccines on the same day. Continuous health insurance enrollment through the control window \nwas required to track both nirsevimab administration and potential adverse events. A self -\ncontrolled risk interval design was used. Infants whose mothers received an RSV vaccine during \npregnancy were excluded from the study.  \nSelf-controlled designs, such as the self -controlled risk interval, are commonly used in vaccine \nsafety studies. These methods compare the risk of adverse events during a period shortly after \nvaccination with that of a later period in the same individual. This controls for fixed \ncharacteristics, such as chronic conditions, that could bias the results. These designs are useful \nbecause people who receive vaccines often differ from those who do not, and those differences \nmay not be fully captured in health rec ords.  \nAge was a significant factor in the design of this study. Diagnoses in the first month of life often \nreflect conditions related to pregnancy, delivery, or newborn care. Healthcare use and insurance \nenrollment patterns also differ in this period. Additional ly, except for the birth dose of hepatitis B, \nroutine vaccines are not given before 38 days of age. For these reasons, safety analyses were \ndone separately for newborns (0 to 37 days) and older infants (38 days to 8 months).  \n36 \n The study assessed seizures, immune thrombocytopenia (ITP), drug reactions, fever, and \nsepsis using self -controlled risk interval designs. Anaphylaxis and non- anaphylactic serious \nallergic reactions were monitored by tracking case counts. Autoimmune and im mune complex \ndiseases are also planned for evaluation through a case- control study at the end of surveillance, \nas these outcomes are rare in infants and may have a delayed onset.  \nA total of 117,427 neonates and infants from birth to under 8 months of age were identified. Following enrollment criteria, 43,532 received nirsevimab. Exclusions included 1,663 infants \nwith prenatal exposure to RSV vaccine, as some may still qualify for nirsevimab under specific \nclinical circumstances. Additional exclusions were made for infants who received nirsevimab at \nthe end of the 2023– 2024 season. The final safety analysis included 9,855 neonates (0 to 37 \ndays old) and 28,054 infants (38 days to under 8 months old).  \nNirsevimab was administered to infants at various ages from birth to under 8 months, with no \nsingle peak age. Dosing clustered in the first week of life and at typical well -child visit intervals, \nincluding 2 weeks, 2 months, 4 months, and 6 months of age.  \nAmong neonates aged 0 to 37 days, administration frequently occurred on the day of birth, often \nwith the hepatitis B vaccine. On day one, most neonates received nirsevimab alone, though \nsome also received hepatitis B. For the remainder of the neonatal peri od, nirsevimab was \ntypically given without same- day hepatitis B vaccination.  \nAmong neonates aged 0 to 37 days, nirsevimab was often administered on the same day as the hepatitis B vaccine, particularly on the day of birth. Among infants aged 38 days to under 8 \nmonths, 84 percent received nirsevimab on the same day as other vaccines . The most common \nsame- day combination included nirsevimab with hepatitis B, rotavirus, DTaP, Hib, \npneumococcal, and polio vaccines.  \nNo significant increased risk of seizures was observed in either the 2023– 2024 or 2024– 2025 \nseasons. Medical record reviews showed that some reported cases were not true seizures, \nwhile others were related to known genetic seizure disorders.  \nRegarding ITP, a single case was identified within the risk window among infants aged 38 days to under 8 months. No cases were observed in the neonatal group.  \nWith respect to drug reactions, there were zero cases in both the risk and control windows for both the neonatal group and the older infant group.  \nAmong neonates aged 0 to 37 days, there were four cases of sepsis or fever in the risk window \nand nine in the control window, yielding a relative risk of 0.44. This outcome was not evaluated \nin older infants due to differences in clinical management of fev er by age. An exploratory \nanalysis showed a numerical imbalance in sepsis workups, such as blood or spinal fluid \ncultures, between risk and control windows. However, medical record review found no \nconsistent concerns, with cultures often performed for reas ons other than fever. No increased \nrisk of sepsis or fever was identified.  \nFor anaphylaxis, no cases were reported in either the neonatal group (0 to 37 days) or the older \ninfant group. For non- anaphylactic serious allergic reactions, there were 14 cases in the \n37 \n neonatal group and 4 in the older group. These were primarily diagnosis codes for urticaria \n(hives) occurring on the same day as nirsevimab administration.  \nDr. Daley summarized that among a combined population of 74,000 neonates and infants \nexposed to nirsevimab over two seasons, there was no increased risk of seizures, ITP, drug \nreactions, fever, or sepsis. No cases of anaphylaxis were reported. A small number of non-\nanaphylactic allergic reactions were observed, primarily coded as urticaria or hives, without more serious hypersensitivity in the same children. These findings support a reassuring safety \nprofile for nirsevimab in routine clinical practice. Addi tional data collection is underway for later -\nseason use, so these results should be considered preliminary.  \nNirsevimab safety surveillance is ongoing. Three assessments were planned: post -2023– 2024 \nresults (already shared with the ACIP RSV Work Group), a preliminary 2024– 2025 assessment \n(presented here), and a final cumulative analysis through July 2025. Medical  records will be \nmanually reviewed for any cases of anaphylaxis or other outcomes of concern. A case -control \nstudy of autoimmune and immune complex diseases was also planned, but only two cases were \nidentified in 2024– 2025, both related to isoimmunization and not associated with nirsevimab. As \na result, this analysis could not be conducted, but the absence of cases is reassuring.  \nDr. Adam MacNeil (CDC/NCIRD) shared the updates and summary of the Evidence to \nRecommendation (EtR) framework for clesrovimab. The policy question under consideration is \nwhether clesrovimab should be recommended for all infants under 8 months of age born during \nor entering their first RSV season.  \nFor the public health problem domain, Dr. MacNeil shared that RSV places a significant burden \non young children. Without preventive products, the CDC estimates RSV caused approximately 2 million medical visits, 58,000 to 80,000 hospitalizations, and 100 to  300 deaths annually in \nU.S. children under five. Most infants are infected in their first year of life, with 2 to 3 percent of \nyoung infants hospitalized. Hospitalization risk is highest in the first months of life and declines with increasing age. About 80 percent of children hospitalized for RSV have no underlying medical conditions; therefore, all young children are at risk for hospitalization. When asked if \nRSV disease  among  infants <8 months of age is of public health importance, the work group \nunanimously voted “yes.”  \nThe benefits and harms domain addressed three key questions: 1) the magnitude of anticipated \nbenefits; 2) the magnitude of anticipated harms; and 3) whether the benefits outweigh the \nharms. To assess this, a GRADE analysis was conducted to evaluate the cer tainty of evidence \nfor both beneficial and harmful outcomes. The PICO components (population, intervention, \ncomparison, outcomes) were defined as follows: the population included all infants under 8 \nmonths of age born during or entering their first RSV season; the intervention was clesrovimab; \nthe comparison was a placebo. Beneficial outcomes assessed included RSV -associated \nmedically attended lower respiratory tract infections (LRTIs), hospitalizations, ICU admissions, \nall-cause medically attended LRTIs, and all -cause LRTI -associated hospitalizations. The \nharmful outcome evaluated was serious adverse events.  \nFor RSV -associated medically attended lower respiratory tract infection (LRTI), the efficacy was \n60%. In the certainty assessment, there was concern for indirectness because the trial excluded \n38 \n infants eligible for palivizumab and was conducted during a season with disrupted RSV \ncirculation due to COVID -19. This concern was noted for all outcomes but was deemed not \nserious. For RSV -associated LRTI with hospitalization, the efficacy was 91%. For R SV-\nassociated LRTI with ICU admission, the efficacy was estimated to be 100%. There was serious concern for imprecision as the confidence interval contained estimates for which different policy \ndecisions may be considered.  \nFor harms, the relative risk of serious adverse events was evaluated through 365 days in the \ntrial. The estimated relative risk was 0.93, with a 95% confidence interval ranging from 0.77 to \n1.2, which included 1, suggesting that serious adverse events occurred at a similar proportion in \nthose who received clesrovimab and those who did not. However, there was a serious concern \nfor imprecision in this estimate, as too few infants were included to capture rare serious adverse \nevents.  \nGRADE findings showed that clesrovimab was effective in preventing RSV -associated medically \nattended LRTI and RSV -associated hospitalization, with high certainty. It was effective in \npreventing ICU admissions due to RSV -associated LRTI with moderate certai nty. It was not \neffective in preventing all -cause medically attended LRTI, with moderate certainty, but was \nmoderately effective in preventing all -cause LRTI -associated hospitalization, with high certainty. \nNo increase in serious adverse events was observed in the clesrovimab group compared to the placebo group with moderate certainty.  \nBeyond trial outcomes, additional benefits of having a second long- acting monoclonal antibody \noption include: having another product with a different binding site in case of resistance \nmutations, supply shortages, and pricing competition. Rates of injection site and systemic reactions were similar between groups (29.9% for clesrovimab vs. 30.9% for placebo), mostly mild or moderate. Fever rates were also similar (3.7% vs. 4.0%), suggesting no increased risk \nwith clesrovimab.  \nBased on the data presented, the work group concluded that clesrovimab is an effective long-acting monoclonal antibody for preventing severe RSV disease in young infants during their first \nRSV season. As the second approved product of its kind, it may be helpful in mitigating any \nsupply disruptions and potential resistance to any single product. Clesrovimab demonstrated a favorable safety profile, with no increase in serious or solicited adverse events, including fever. \nHowever, rare events may not have been detected due to the trial's size. The majority of the \nwork group agreed that the anticipated benefits were large and the harms minimal. The group \nunanimously concluded that the benefits outweigh the risks.  \nFor the values domain, data was presented on parents' and caregivers' views of the benefits of \nclesrovimab relative to its harms. A national survey conducted from December 2022 to January \n2023 among pregnant and postpartum women found that 31% knew a baby hospitalized with RSV, 38% believed their baby would become moderately or severely ill if infected, and 69% \nwere concerned about possible hospitalization. In a study conducted in April and May in \nCascadia on parental preferences for RSV products, 37% preferred maternal vaccination, 12% preferred the infant monoclonal antibody, 3% preferred neither, and 48% had no preference, \nsuggesting that either option may be acceptable to parents. Preliminary data from the National \n39 \n Immunization Survey showed that as of February, 50% of infants under 8 months had received \na long- acting monoclonal antibody, and another 7% of caregivers reported definite intentions to \ndo so.  \nThe work group felt that parents and caregivers probably viewed the desirable effects of \nclesrovimab as large relative to the undesirable effects. When asked whether there was \nimportant uncertainty or variability in how much parents and caregivers value the prevention of severe RSV disease, the majority of the work group felt there was probably not significant \nuncertainty or variability.  \nIn the acceptability domain, data assessed whether clesrovimab is acceptable to key \nstakeholders, primarily providers and professional organizations. In a survey of 200 U.S. \npediatricians conducted in October 2024, about 75% reported offering a long- acting monoclonal \nantibody in their practice. Over 90% agreed or strongly agreed that it is safe for infants, effective \nagainst severe RSV disease, and that they felt confident recommending and co- administering it \nwith other vaccines. National organizations, inc luding the American Academy of Pediatrics, the \nAmerican Academy of Family Physicians, and the National Foundation for Infectious Diseases, \nhave endorsed clesrovimab. The majority of the work group felt that clesrovimab is acceptable \nto key stakeholders. A minority of the work group said it is probably acceptable.  \nIn the feasibility domain, the data focused on whether clesrovimab is practical to implement for \nall infants under 8 months of age born during or entering their first RSV season. If recommended by ACIP, clesrovimab would become the second long- acting monoc lonal \nantibody included in the Vaccines for Children (VFC) program, which provides vaccines at no cost to eligible children. The product is a single- dose immunization, administered regardless of \ninfant weight, which may simplify delivery. However, stocking could be a challenge for providers \nwho also need to carry nirsevimab for high- risk children aged 8 through 19 months. Some may \nprefer to stock only one long- acting RSV monoclonal antibody. In a 2024 survey of pediatricians, \nthe most frequently reported im plementation challenges were determining maternal RSV \nvaccination status (34%), the financial burden of purchasing the product, and reimbursement issues from private insurers. The majority of the work group felt that clesrovimab is, or probably \nis, feasible to implement.  \nFor the resource use domain, a cost -effectiveness model was developed by the University of \nMichigan and the CDC, building on methods previously used to evaluate nirsevimab. The model \nwas updated with key inputs for clesrovimab, including its effectiveness and anticipated cost per dose. In the base case scenario, assuming 50% coverage of clesrovimab among an annual \nbirth cohort and continued use of palivizumab for eligible high- risk infants, the model estimated \nprevention of approximately 120,000 outpatient visits, 43,500 emergency department visits, \n20,000 hospitalizations, 4,500 ICU admissions, 20 deaths, and nearly 3,500 quality -adjusted life \nyears (QALYs) gained.  \nEstimated incremental cost -effectiveness ratios were roughly $3,000 per outpatient visit \nprevented, $8,200 per emergency department visit prevented, $17,500 per hospitalization prevented, $80,000 per ICU admission prevented, and $104,500 per quality -adjusted  year of life \n(QALY)  gained. Extensive sensitivity analyses were conducted using a wide range of input \n40 \n values. Results were sensitive to assumptions about inpatient costs, quality of life losses, and \nproduct price.  \nThe majority of the work group felt that clesrovimab use among all infants under 8 months of \nage born during or entering their first RSV season is, or probably is, a reasonable and efficient \nallocation of resources at an average cost of $458 per dose.  \nDr. MacNeil summarized the work group’s discussion, considerations, and interpretation of the \ndata. The group found that the phase 2b/3 trial of clesrovimab demonstrated high efficacy in \npreventing severe RSV through 150 days. Serious adverse events appear ed to be balanced \nbetween the clesrovimab and placebo groups, although rare events may not be detectable in a trial of this size. The group noted that while clesrovimab has a shorter half -life than nirsevimab, \nits efficacy appeared sustained through 150 days. Direct comparisons between the two products \nare limited due to differences in trial endpoints; a head- to-head study would be needed to \nevaluate comparative efficacy.  \nThe group emphasized the value of having multiple long- acting monoclonal antibody products \nand manufacturers, as this diversification supports resilience in the face of potential resistance or supply shortages and may help drive price competition. RSV remains the leading cause of \nhospitalization in infants, and immunization can significantly reduce this burden. To achieve a \nmeaningful public health impact, timely administration is critical. For infants born outside the \nRSV season, high coverage before the s eason begins is essential. For those born during the \nseason, administration should ideally occur within the first week of life, preferably during the \nhospitalization for birth.  \nWhen asked about the balance between desirable and undesirable effects, the work group \nconcluded that the desirable consequences clearly outweigh the undesirable ones. In the final \npoll, the work group unanimously supported recommending clesrovimab for all  infants under 8 \nmonths of age born during or entering their first RSV season.  \nDr. Adam MacNeil (CDC/NCIRD) shared the updates on clinical considerations for clesrovimab. \nTo summarize the effectiveness, uptake, and impact data: Nirsevimab was effective in \npreventing RSV -associated emergency department visits, hospitalizations, and cr itical illness \namong infants in their first RSV season. Maternal vaccination was effective against RSV -\nassociated emergency visits and hospitalizations. An estimated 50% of infants were either born \nto a vaccinated mother or received nirsevimab. Following t he introduction of RSV immunization, \nhospitalization rates declined by 30% to 40% among eligible infants and by 50% among infants \naged 0 to 2 months.  \nThe work group noted that the impact of RSV immunizations in reducing severe disease among \ninfants during the 2024– 2025 season in the RSV -NET and NVSN networks is clear. Increasing \nuptake is crucial to further reduce the burden of RSV. A greater impact has  been observed in \ncountries with higher immunization coverage. Maximizing availability, including providing the \ninfant RSV antibody during the birth hospitalization, is important. Expanding birthing hospital \nenrollment in the VFC program is a crucial step,  although challenges remain, and continued \nefforts are necessary to increase participation.  \nTo summarize the FAERS post -marketing data for nirsevimab: Since approval through March \n31, 2025, the most frequently reported adverse events involved RSV infections occurring after \nnirsevimab administration, including related symptoms and complications. N o new safety \n41 \n labeling updates have been made since the addition of serious hypersensitivity reactions on \nFebruary 23, 2024. No additional safety signals have been identified. Errors involving incorrect \ndosing or product selection continue to be reported. FDA will conti nue routine \npharmacovigilance for nirsevimab.  \nThe VSD nirsevimab safety study for the 2024– 2025 season included nearly 40,000 infants and \nemployed a self -controlled risk interval design. No increased risk was observed for seizures, \nimmune thrombocytopenia, drug reactions, sepsis, or fever. No cases of  anaphylaxis were \nreported, and 18 cases of allergic reactions, primarily hives, were identified.  \nThe work group found that FAERS and VSD safety data are reassuring and emphasized the \nimportance of continued safety monitoring.  \nThe VSD maternal RSV vaccine study included a matched cohort of 14,000 pregnant women \nwho were either vaccinated or unvaccinated. No increased risk was observed for most \noutcomes. An association was identified between maternal RSV vaccination and hypertens ive \ndisorders of pregnancy, including preeclampsia, although the severity of the episodes of \nhypertensive disorders of pregnancy was similar among vaccinated and unvaccinated. VSD \nnoted potential residual confounding, such as parity, and possible outcome m isclassification due \nto challenges in determining the timing of onset and the absence of medical chart review.  \nThe work group found the overall study findings reassuring, particularly the lack of association between maternal RSV vaccination and preterm birth. The group continued to conclude that the \nbenefits of maternal RSV vaccination clearly outweigh the potential risks. Opinions were divided \non the importance of the observed association with hypertensive disorders of pregnancy. Some \nmembers were not concerned, noting the small effect size, the absence of an increase in \nseverity among vaccinated individuals, and t he lack of association with preterm birth. The \nAmerican College of Obstetricians and Gynecologists agreed with this assessment. Some were \nconcerned that an imbalance of HDP was seen in multiple studies (phase 3 clinical trial, \npublished retrospective cohor t study, post -marketing study), and felt it was important that \nhealthcare providers discuss the potential risk of HDP with pregnant women.  \nClesrovimab is a long- lasting monoclonal antibody manufactured by Merck and is a form of \npassive immunization. It is administered as a single 105 mg dose in a 0.7 mL prefilled syringe, \nwith the same dose recommended for all infants born during or entering their first RSV season, \nregardless of weight.  \nDr. Adam MacNeil (CDC/NCIRD) presented the proposed recommendations. Clesrovimab and \nnirsevimab are recommended for use in infants under 8 months of age who are born during or \nentering their first RSV season. There is no preferential recommendation between the two \nproducts.  \nOnly nirsevimab is recommended for children aged 8 through 19 months who are at increased \nrisk of severe RSV disease and entering their second RSV season. Infants eligible for \nnirsevimab in their second season may have received either clesrovimab or nirsev imab during \ntheir first season. There are no safety or effectiveness concerns with using clesrovimab in the \nfirst season and nirsevimab in the second.  \nThe proposed use of RSV antibody immunizations in infants, including nirsevimab or \nclesrovimab, is largely consistent with current nirsevimab recommendations. One dose is \nrecommended for infants under 8 months of age during or entering their first RSV seas on, \ntypically October through March in most of the continental U.S., if the mother did not receive RSV vaccine during pregnancy, if maternal vaccination status is unknown, or if the infant was \nborn less than 14 days after maternal vaccination. Use may also be considered for infants born \nto mothers with reduced immune response or impaired antibody transfer, or for infants with \n42 \n conditions that lead to loss of maternal antibodies, or infants with substantially increased risk for \nsevere RSV disease.  \nTo prevent severe RSV in infants, most will not need both maternal vaccination and an RSV \nantibody. Pregnant women should work with their healthcare provider to choose one of the two \noptions.  \nMaternal RSV vaccine is recommended from September through January, and infant RSV \nantibodies are recommended from October through March. For infants already born before \nOctober, the optimal time to administer RSV antibody is just before the start of the s eason. In \nareas with varying RSV seasonality, providers should follow guidance from their state, local, or \nterritorial health authorities.  \nAdministration errors have occurred, including the incorrect distribution of RSV immunization \nproducts to the wrong population. Only RSV antibodies should be given to infants. RSV \nvaccines, such as Abrysvo, Arexvy, and mResvia, should not be administered t o children. Only \nAbrysvo is approved for use in pregnant women. Arexvy and mResvia should not be given \nduring pregnancy. Older adults may receive any of the three approved RSV vaccines. RSV \nantibodies should not be administered to pregnant women or older adults.  \nIf an infant or child receives either nirsevimab or clesrovimab, palivizumab is not recommended \nduring the same RSV season. Clesrovimab will be administered in the same manner as \nnirsevimab, as an intramuscular injection into the vastus lateralis muscle of  the anterolateral \nthigh. The gluteal muscle should not be used for administration. It is acceptable to administer \ninfant RSV antibodies concurrently with routine vaccines.  \nClesrovimab should be stored in a refrigerator and used within 48 hours of being removed. It should not be frozen, shaken, or exposed to light.  \nIf RSV antibodies are administered alone, suspected adverse events should be reported to \nMedWatch. If they are given at the same time as any vaccine, suspected adverse events should \nbe reported to the VAERS. Additional reporting to MedWatch is not necessar y in that case.  \nProposed Recommendation:  \nACIP recommends that infants aged<8 months born during or entering their first RSV \nseason who are not protected by maternal vaccination receive one dose of clesrovimab.  \nDr. Georgina Peacock (CDC/NCIRD) shared updates on the RSV vaccines VFC resolution. The \npurpose of the resolution is to update the existing policy to include an additional long- acting \nmonoclonal antibody for the prevention of RSV.  \nThe first component of the resolution addresses the RSV maternal vaccine. There are no \nchanges to the eligible groups, recommended schedule, or dosing intervals. However, the name \nof the individual product has been replaced with a product group name to ref lect the availability \nof two licensed products. There are also no changes to the dosage, contraindications, or \nprecautions.  \nThe second component of the resolution has been retitled to reflect a product group name \ninstead of a specific product. The eligible groups remain unchanged, as does the list of children at increased risk for severe RSV disease. The recommended schedule an d intervals for \nnirsevimab are unchanged. A new row has been added to the table to include clesrovimab, the newly licensed long- acting monoclonal antibody for RSV prevention. As noted, clesrovimab is \nnot indicated for use during a second RSV season.  \n43 \n Table notes have been added to define long -acting monoclonal antibodies and to provide a link \nto published information on the timing of administration. The language below the table has also \nbeen updated to reference the product group rather than an individual product. There are no \nchanges to dosage, contraindications, or precautions.  \nFinally, ACIP recommendations published within six months of the resolution will be incorporated by reference, except for changes related to eligible groups.  \nProposed Recommendation: VFC update  \n Approve the updated Vaccines for Children (VFC) resolution for prevention of RSV . \nDr. Levi acknowledged the consensus that RSV is a serious illness, particularly for young infants \nand those with underlying health conditions or born preterm. He expressed hope that newly \ndeveloped RSV therapies will help prevent severe outcomes, including hospitalizations and \ndeaths. However, he raised concerns based on clinical trial data related to the safety of these \nproducts. In the Melody trial, which tested nirsevimab in healthy infants, there were five deaths \nin the immunized group and none in the placebo group. Although serious adverse events \n(SAEs) were balanced overall, nervous system -related SAEs appeared more frequently in the \nimmunized group. He noted that two deaths due to gastroenteritis in healthy infants were \nparticularly unusual. In the Medley trial, which involved high- risk infants and compared \nnirsevimab to palivizumab, the imbalance in deaths continued (five in the immunized group \nversus one in the comparator group), with similar patterns in nervous system SAEs and gastroenteritis cases.  The Harmony trial, conducted in Europe, showed no deaths in either \ngroup but still reflected a higher rate of SAEs in the immunized group, particularly involving the nervous system. Dr. Levi also highlighted data from the clinical trial of clesrovimab, the product under current consideration. In that trial, there were seven deaths in the immunized group compared to three in the control group. Nervous system SAEs were reported in 25 immunized \ninfants versus four in the control group, and gastroenteritis cas es occurred in 30 versus 10 \ninfants. He pointed out the higher dose used for clesrovimab (105 mg) compared to nirsevimab \n(50 to 100 mg), suggesting the need to examine potential dose -related effects. Additionally, \nearly reports from the Melody trial sugges ted that immunized infants had longer hospital stays \nupon admission, raising concerns about the potential for immunization- enhanced disease. Dr. \nLevi concluded by asking whether these patterns, though based on small numbers, might signal potential safety c oncerns. He noted that post -marketing analyses presented so far have been \nlimited in scope and duration, and he urged CDC and committee colleagues to consider whether \nthe observed imbalances warrant further investigation alongside the recognized benefits.  \nA representative from Merck Research Laboratories spoke about clesrovimab, a monoclonal \nantibody recently licensed by the FDA for the prevention of RSV disease in infants entering their first RSV season. The representative explained that the FDA conducted a thorough review of the product’s safety and efficacy data and that Merck had shared detailed materials with the \nACIP working group during its deliberations in November of the previous year. They emphasized \nthat all adverse events reported during the clinical trials were extensively evaluated, and none were found by investigators to be related to RSV or the intervention given to the infants. No patterns or trends were observed in terms of cause, affected organ systems, or timing of events. \nThe representati ve also pointed out that the main trial in healthy infants, known as Protocol 4 or \n44 \n CLEVER, used a 2:1 randomization ratio, which should be considered when interpreting event \nnumbers.  \nA member of the Maternal/Pediatric Workgroup addressed concerns about deaths observed in \nthe pivotal Phase 2b/3 trial of clesrovimab. They noted that deaths were evaluated as potential \nharm over the 365 days following immunization. The events were balanced  between the \nclesrovimab and placebo groups when accounting for the study's 2:1 randomization ratio. \nSpecifically, there were seven deaths in the clesrovimab group and three in the placebo group, \nwhich aligns with the expected distribution based on the tri al design. No patterns were observed \nin the cause or timing of deaths that suggested a link to the intervention.  \nAn ex officio member clarified that clesrovimab was approved by the Center for Drug Evaluation \nand Research (CDER). As someone who works within CDER, they explained that they preferred not to speak on behalf of the review team and instead suggested deferri ng to CDER for an \nofficial comment on the safety review.  \nMs. Hodowanik stated that she did not have much to add beyond Merck’s summary but emphasized that the FDA carefully reviewed all case narratives. She confirmed that no trends or clustering were observed in the causes of death, and there was nothing to suggest a drug -\nrelated cause in any of the cases. She also noted that clesrovimab is a monoclonal antibody \nand that this class of products is generally well tolerated with limited toxicity.  \nDr. Levi thanked the group for their responses and acknowledged the 2:1 randomization ratio \nused in the trials. However, he raised a concern about a possible trend in the data. He noted \nthat across four separate trials, the number of deaths consistently oc curred more frequently in \nthe immunized groups. While he agreed that the trials were small and not powered to detect \nmost safety signals unless those signals were very strong, he questioned whether seeing a \nsimilar pattern across multiple studies involving two similar products should prompt further \nconsideration. He asked the group for their thoughts on whether this recurring outcome might be \nmeaningful.  \nMs. Hodowanik responded by acknowledging that the numerical counts of deaths in the studies \nappeared higher in the immunized groups. Still, she emphasized that the actual percentages \nwere very close, at 0.3% versus 0.2%. She stated that this would not be c onsidered a \nmeaningful difference in death rates between the study arms. She noted that these are very \nsmall numbers and do not indicate a significant trend. Additionally, she explained that the FDA \nplaced significant weight on reviewing the narratives of each case and assessing the potential biological plausibility between the causes of death and the administration of clesrovimab. No \nsuch connections were identified in their review.  \nDr. Kulldorff commented that among the four trials discussed, three involved nirsevimab, which \nhas already been recommended by ACIP and is not under consideration for a vote in the current \nmeeting. He noted that the observed imbalances in those trials are important and should be \nclosely monitored moving forward, particularly regarding mortality and other potential adverse \nevents associated with nirsevimab. He clarified that the current vote pertains to clesrovimab, and based on the data presented, mortality  appeared to be more balanced between the study \narms for this product. Dr. Kulldorff suggested that it is possible clesrovimab may prove to be \n45 \n superior to nirsevimab, although this is not yet known. He emphasized the importance of \ncontinuing to evaluate both products during the upcoming RSV season.  \nDr. Levi requested clarification to ensure his understanding was accurate. He inquired whether \nthere is currently an ongoing trial for clesrovimab in which the most recent reporting shows eight \ndeaths in the immunized group compared to four deaths in the non- immunized group receiving \nstandard care. He asked if that was an accurate interpretation of the available data.  \nA representative from Merck confirmed that, in addition to the healthy infant study (Protocol 4, also known as CLEVER), there is an ongoing trial in at -risk infants called Protocol 7, also \nreferred to as SMART. In this study, infants are randomized one -to-one to receive either \nclesrovimab or palivizumab. An interim analysis was conducted to support FDA licensure, and \nas noted, it showed eight deaths in the clesrovimab arm and four in the palivizumab arm. Each of these deaths was thoroughly evaluated and rev iewed by an independent external data \nmonitoring committee. As with the earlier trial, no deaths were attributed to the study \nintervention. There was no evidence of clustering by cause, system organ class, or timing of the \nevents. The representative emphas ized that these events are rare and that the study remains \nongoing.  \nDr. Meissner stated that these issues were thoroughly discussed within the workgroup, which \nincluded over 60 members. He emphasized that the group carefully reviewed all available data \nin detail and appreciated Dr. Levi's close examination of the records. However, he noted that the workgroup was comfortable with the findings from the clesrovimab trials. He acknowledged that \nstudies involving high- risk infants, including those born preterm, involve a particularly fragile \npopulation where unexpected deaths can unfortunately occur in both treatment and control \ngroups. Dr. Meissner reiterated that there was no evidence of an imbalance or pattern in serious adverse events among clesrovimab recipients. He concluded by affirming the workgroup’s \nconfidence in the recommendation they made.  \nDr. Kulldorff expressed his gratitude to the work group, noting that the effort involved not only Dr. Meissner but many others who worked very hard on this review. He also thanked his fellow \nACIP committee members, noting that while the presentations from the previous day primarily \nfocused on the maternal vaccine and nirsevimab, which had already been recommended in a prior meeting, the work group members went beyond that information. They examined the data \non clesrovimab in great detail, which is the produ ct currently under consideration and was \nrecently approved by the FDA. He commended the committee for stepping in and conducting a \nvery thorough review.  \nDr. Malone stated that there has been very active discussion and consideration within the \ncommittee regarding this product. For the record, he emphasized that the topic has been \nthoroughly debated internally. Despite the short timeframe available to addres s it, he expressed \nconfidence that the committee had sufficient information. He noted that the committee had \nrigorously considered the various aspects of the product, had been appropriately briefed on the \nunderlying issues and science, and had taken the ti me to investigate and discuss the matter to \nthe best of its ability.  \n46 \n Dr. Hopkins, representing the National Foundation for Infectious Diseases, emphasized that \nRSV is the leading cause of hospitalizations in infants in the United States. He stated that the \nscientific evidence clearly supports the use of maternal RSV vaccines during pregnancy, as well \nas monoclonal antibodies for infants whose mothers were not vaccinated. He urged ACIP to ensure that any changes to RSV recommendations remain grounded in evidence. He reaffirmed \nNFID’s commitment to protecting infants from seri ous RSV -related outcomes.  \nDr. Levi shared a personal perspective, noting that while he is a scientist, he is also a father of \nsix children. He emphasized the importance of considering the parents' viewpoint when \nevaluating the data. Reflecting on his own experience, he explained that if he were the parent of \na baby born prematurely or with underlying health conditions, he would likely choose to use \nthese products, given the serious threat RSV can pose to vulnerable infants. However, he stated that if his child were healthy and born full- term, he would feel hesitant about using a new \nproduct, even with scientific knowledge in hand. He expressed concern about introducing an \nimmunization for a disease that has historically presented challenges in vaccine development. \nDr. Levi emphasized that, beyond metrics such as hospitalization and disease burden, it is \ncrucial to consider how parents might perceive and respond to the available data. He concluded \nby acknowledging that, as a father, he would feel cautious in such a situation and wanted to \nshare that perspective with the committee.  \nDr. Pepsworth asked for clarification on the differences in health outcomes between very sick \ninfants and healthy children. She also inquired about available data on the effectiveness and \nsafety of clesrovimab when administered according to the current imm unization schedule. \nSpecifically, she questioned whether there is information on the safety of administering \nclesrovimab concurrently with other routine vaccines, including those for hepatitis B, rotavirus, \nDTaP, Hib, pneumococcal, polio, COVID -19, and inf luenza. She emphasized the importance of \nunderstanding how simultaneous administration may impact safety outcomes.  \nDr. Meissner responded by explaining that approximately 80% of children hospitalized for RSV are otherwise healthy, without prematurity, congenital heart disease, or chronic lung disease. \nThese infants typically become symptomatic when infected, and about one -third of RSV cases \nin children lead to lower respiratory tract infections that require medical attention, such as visits to a pediatrician or the emergency department, even if hospitalization is not required. He \nemphasized that it is currently not poss ible to predict which healthy infants will develop severe \ndisease, making it difficult to target monoclonal antibody use solely based on known risk factors. \nWhile RSV -related deaths in infants are very rare in the United States, with fewer than 100 \nannuall y and mostly among those with comorbidities, hospitalization is the most reliable primary \nendpoint to assess product effectiveness, with ICU admissions also being monitored. He \nclarified that products like clesrovimab and nirsevimab are monoclonal antibodi es administered \npassively and are not vaccines in the traditional sense, as they do not stimulate an immune \nresponse. He addressed maternal vaccination, stating that if a pregnant woman chooses not to \nreceive an RSV vaccine between 32 and 36 weeks of gestation, the alternative is to administer a monoclonal antibody to the infant at birth. He added that if he were Dr. Levi’s pediatrician, he \nwould strongly recommend that his wife either receive the maternal RSV vaccine or that the \nnewborn receive a monoclonal antibody. He expressed strong support for the progress made in \n47 \n RSV prevention, crediting much of it to the work of Barney Graham, who received NIH support. \nHe described the new monoclonal antibody products and vaccines as remarkable, both safe \nand effective. He stated that the work group and the FDA had conducted extensive reviews, \nleaving no unresolved safety or efficacy issues in his view.  \nDr. Kulldorff addressed Dr. Pebsworth’s question about the concomitant administration of \nmonoclonal antibodies with routine childhood vaccines given on the same day. He noted that the work group had reviewed this issue and requested follow -up from Dr. Meis sner to provide \nadditional context and information.  \nDr. Meissner explained that there are three monoclonal antibodies used for the prevention of \nRSV. Palivizumab was the first -generation product, introduced around 1999, while clesrovimab \nand nirsevimab are second- generation antibodies that incorporate speci fic mutations in the Fc \nfragment, extending their half -lives. This allows a single dose to protect throughout the RSV \nseason. In contrast, palivizumab required monthly dosing for five months to maintain coverage \nduring the season. He noted that there is ex tensive experience with palivizumab, and despite its \nrepeated dosing schedule, no interference has been observed with any of the standard, \nroutinely recommended childhood vaccines. Based on this experience, he expressed \nconfidence that concomitant administ ration with other vaccines is not a concern.  \nDr. Goldman, representing the American College of Physicians and speaking as an individual, \nexpressed support for the intervention under consideration. He thanked Dr. Meissner for his earlier remarks and added that, as a clinician, he sees firsthand the im pact of diseases when \nthey are not prevented or treated. He emphasized that healthy children do get RSV, and some become seriously ill, are hospitalized, or even die. He cautioned against limiting interventions only to those identified as high- risk, since risk is often not fully understood until illness occurs. \nHe noted that this product is not a vaccine but rather provides passive immunity. As a father of \ntwo children, he wished it had been available when they were born. He called the product a major advancement in medical science and urged the committee to approve the resolution to \nhelp protect children and keep them healthy.  \nDr. Meyer addressed Dr. Pepsworth’s earlier question about the co -administration of monoclonal \nantibodies with other vaccines. She noted that real -world evidence from the Vaccine Safety \nDatalink, presented by Dr. Daly the previous day, showed that a high proportion of infants had \nreceived clesrovimab at the same time as another routine vaccine. She then turned the \ndiscussion over to Dr. Daly to provide further details from the real -world data.  \nDr. Daley explained that the safety data presented the previous day covered approximately 74,000 infants who received nirsevimab, making the dataset roughly 20 times larger than the \noriginal clinical trial. This data reflects real -world use in routine prac tice. He highlighted that \namong the neonate cohort, 20 percent received same- day hepatitis B vaccination, and among \nthe older infant group, 84 percent received same -day vaccination with routine childhood \nvaccines. He concluded that the safety evidence, par ticularly for infants aged 37 days to less \nthan 8 months, does include and support safety with simultaneous vaccination.  \nDr. Malone shared a concern raised by colleagues in the medical community, particularly among primary care providers, about the possibility that monoclonal antibody products may simply \n48 \n delay RSV infection from the first year of life to the second. He noted that Dr. Meissner had \npreviously discussed the current understanding of RSV pathophysiology and asked him to address this issue. Specifically, he requested that Dr. Meissner explain the role of terminal micro airway development in infants and how it relates to the effectiveness and implications of \nadministering this product during early infancy. \nDr. Meissner explained that the most severe RSV disease typically occurs in the first 90 days of \nlife, as this is when infants are at the highest risk of hospitalization. The increased risk is due to the small size of their bronchioles, which are the narrow airways that conduct air into the alveoli, the tiny air sacs in the lungs where oxygen and carbon dioxide are exchanged. In very young or \npreterm infants, these small airways can become completely blocked by inflammation during an \nRSV lower respiratory tract infection. By the second year of life, a child’s airways are larger, making it much less likely that a small amount of inflammation will cause significant respiratory distress. Monoclonal antibodies are given to healthy infants to prevent RSV infection during the highest -risk period, particularly the first 90 days. Dr. Meissner noted that these antibodies do not \nfully prevent infection but instead reduce the likelihood of lower respiratory tract disease, allowing the child to build natural immunity. This may offer protection in the second year of life. Even if infection shifts to the second year, it is generally less problematic because the airways \nare larger and better able to tolerate inflammation without becoming obstructed.  \nDr. Meissner recognized the contributions of Jefferson Jones, who led the work group throughout the process and was praised for doing an exemplary job.  \nDr. Levi encouraged CDC colleagues to expand post -marketing analyses to include data on \ndeaths and a broader range of potential adverse events. He emphasized the importance of \nunderstanding the risks alongside the benefits, regardless of the decision to use the product. He emphasized the importance of transparency in assessing the trade- offs involved. While he \nacknowledged that the analysis presented the previous day was very well done, he noted that it was limited in scope, focusing only on specific periods and certain adverse events, and \nexpressed hope that future analyses would be more comprehensive.  \nDr. Kulldorff expressed his deep appreciation to the work group for their thorough efforts, to the \nCDC staff for their support, and especially to his fellow committee members. He acknowledged that, despite very short notice, the group fully engaged with the review of clesrovimab, which \nwas only approved by the FDA 16 days prior. He recognized the challenge of gathering and \nreviewing a large amount of information in a limited timeframe and thanked everyone for their \ncommitment to carefully evaluating all the available data.  \nVote: RSV Maternal/Pediatric Vote  \n \nDr. Martin Kulldorff (ACIP Chair) read the following proposed ACIP voting language for the \nRSV Maternal/Pediatric vaccine into the record:  \n \nA\nCIP recommends infants aged <8 months born during or entering their first RSV \nseason who are not protected by maternal vaccination receive one dose of \nclesrovimab.  \n49 \n  \n \nMotion/Vote: RSV Vaccines   \n \nDr. Malone motioned to approve the recommended voting language, stating, ”ACIP \nrecommends infants aged <8 months born during or entering their first RSV season who are \nnot protected by maternal vaccination receive one dose of clesrovimab. ” Dr. Pagano \nsecon ded the motion. No COIs were declared. The motion carried with 5 in favor and 2 \nopposed. The disposition of the vote was as follows:  \n \n   5 Favored:  Malone, Hibbleln, Pagano, Meissner, Kulldorff  \n    2 Opposed:   Levi, Pebsworth  \n    0 Abstained:   \n \nVote:\n RSV Maternal/Pediatric- VFC Vote  \n \nDr. Martin Kulldorff (ACIP Chair) read the following proposed ACIP VFC vote for RSV \nMaternal/Pediatric into the record:  \n \nA\npprove the updated Vaccines for Children (VFC) resolution for prevention of RSV .  \n \n \nMotion/Vote: RSV Vaccines   \n \nDr. Malone motioned to approve the recommended updated Vaccines for Children (VFC) \nresolution for prevention of RSV . Dr. Pagano seconded the motion. No COIs were declared. \nThe motion carried with 15 in favor and 0 opposed. The disposition of the vote was as \nfollows:  \n \n    7 Favored:  Malone, Hibbleln, Pagano, Levi, Meissner, Pebsworth, Kulldorff  \n    0 Opposed:      \n    0 Abstained:   \n \n*Dr. Pebsworth disclosed that she owns shares in a healthcare sector fund that includes holdings relevant \nto ACIP discussions, including vaccine manufacturers. However, the value of these holdings falls below \nthe de minimis threshold set by the Office of Government Ethics. Based on this, she confirmed her understanding that she is permitted to participate in the ACIP meeting fully.\n \nPUBLIC C OMMENT  \n \nThe f\nloor was opened for public comment on June 25, 2025. The comments made during the \nmeeting are summarized in this document. Members of the public were also invited to submit \nwritten public comments to ACIP through the Federal eRulemaking Portal under Docket Number \nID CDC- 2025- 0024. Visit regulations.gov  for access to read the comments received.  \n50 \n Kim Mack Rosenberg, Esq.  \nChildren’s Health Defense and Mack Rosenberg Law LLC  \n \nA\n representative from Children’s Health Defense provided public comment expressing concern \nover the misuse of ACIP’s best practice guidelines by several states, including California and \nNew York, to restrict medical exemptions for school vaccine requiremen ts. The commenter \nnoted that ACIP guidelines define contraindications and precautions broadly, recognizing that \nthe lists are not exhaustive and cannot account for every circumstance in which a child may \nneed a medical exemption. However, many states and school districts are limiting exemptions to \nonly those explicitly listed, or even further restricting them to cases of anaphylaxis, disregarding \nother serious medical risks identified by treating physicians. The speaker urged ACIP to amend its best practices guidelines or issue a public statement clarifying that the CDC is not authorized \nto provide individualized medical advice and that clinical decisions regarding exemptions should \nbe made by treating physicians using CDC guidance, medical history, and clinical judgment. The \ncommenter shared the case of a 16 -year-old student in New York with multiple health \nconditions, including acquired von Willebrand’s disease and a history of severe vaccine reactions. Despite certifications from six licensed physicians stating that a third hepatitis B \nvaccine dose could endanger her life, her school district denied the exemption because her conditions are not explicitly listed as contraindications by ACIP. The commenter emphasized \nthat similar cases occur frequently, and some children have suffered serious injuries after being \nforced to vaccinate against medical advice. The speaker concluded by urging ACIP to act \npromptly to clarify its guidelines and protect both vulnerable students and physician autonomy.  \nChrissie Juliano, MPP  \nBig Cities Health Coalition  \n \nC\nhrissie Juliano, Executive Director of the Big Cities Health Coalition (BCHC), provided public \ncomment expressing concern over Secretary Kennedy’s recent dismissal of all 17 prior ACIP \nmembers, including Dr. Mysheika Roberts, Columbus Health Commissioner and BCHC board member, who was scheduled to join the committee. Juliano emphasized the critical role of local \nhealth departments in vaccination efforts and the trusted relationships they build with \ncommunities. She stressed that ACIP’s independent, science- based vaccine recommendations \nhave guided public health for over 60 years, and sudden leadership changes risk increasing confusion and public distrust at a time when vaccine confidence is already fragile. She highlighted the resurgence of vaccine- preventa ble diseases, such as measles, and underscored \nthe importance of maintaining equitable access to routine vaccines. Juliano urged the new committee members to continue ACIP’s tradition of making decisions based on science and \nevidence to protect public health.  \n \nD\nr. Mary Koslap -Petraco \nPediatric Nurse Practitioner House Calls  \n \nDr\n. Mary Koslap -Petraco, a pediatric nurse practitioner with over 30 years of experience, \nprovided public comment expressing concern about the recent dismissal of 17 ACIP members. She stated that the former members had the expertise to design vaccine studi es and voiced \nconcern that the current committee has misinterpreted VAERS data, which provides safety \nsignals but does not establish causality. Dr. Koslap- Petraco emphasized the need to keep \nCOVID -19 vaccines available for children who need them, noting that misinformation has led \nparents to lose trust in healthcare providers. She shared personal experiences with vaccine-\npreventable diseases in her own family. She warned that if access to vaccines is reduced, more \nchildren will suffer and die from diseases that are currently preventable. As a Vaccines for \n51 \n Children (VFC) provider, she urged ACIP to continue ensuring that all children have access to \nlife-saving vaccines.  \n \nM\narcia Cohen Zakai  \nPrivate Citizen  \n \nM\narcia Cohen Zakai provided public comments, questioning the recent dismissal of all 17 ACIP \nmembers and calling the action unjustified, while raising concerns about its impact on public trust. She referenced a letter from the California Medical Association, the American Medical \nAssociation, and over 100 other medical organizations urging the reinstatement of the \ndismissed members. Zakai stressed that ACIP’s evidence- based recommendations have \nhistorically ensured access to FDA -approved vaccines through a transparent process, and that \nthe current vacancies risk creating confusion and undermining vaccine confidence. She warned that this could lead to preventable illness, disability, and death. Zakai emphasized the urgent \nneed for expert vaccine guidance, especially amid ongoing COVID -19 and measles outbreaks, \nto protect the public and maintain widespread access to life- saving vaccines.  \n \nC\naroline Brown, MD  \nThe Children’s Clinic of Winston Salem  \n \nD\nr. Caroline Brown, a general pediatrician from North Carolina, provided public comment \nexpressing deep concern about declining vaccination rates and the resurgence of vaccine-\npreventable diseases. Drawing from nearly two decades of clinical experience, she described firsthand encounters with severe illness in children, including cases of RSV, pertussis, and \ncomplications from diseases now preventable by vaccines. She noted that when she trained in \nthe early 2000s, routine spinal taps were performed on febr ile infants to rule out meningitis. Still, \nvaccines like Hib and pneumococcal conjugate have since spared many children from such procedures and outcomes. Dr. Brown reported that just one day before the meeting, the first confirmed case of measles was announced in her county. She has since been responding to \nconcerned parents in her community. She emphasized that measles was eradicated in the \nUnited States 25 years ago. Still, its return is a direct result of declining vaccine uptake driven \nby misinformatio n, some of which she stated is amplified by members of the committee itself.  \n \n \nD\nr. Alexandra Jones Packham  \nPrivate Citizen  \n \nD\nr. Alexandra Jones Packham, a recent medical school graduate and incoming resident in \ninternal medicine and pediatrics, provided public comment. She shared that she is currently \npregnant and due in the middle of respiratory season, giving her a unique perspective as both a \nfuture pediatrician and a soon- to-be mother. Reflecting on her medical training, she described \nher experience in the pediatric ICU during the winter, where she saw numerous cases of bronchiolitis caused by RSV and influenza. She emphasized the limited treatment options for \nthese infections, noting that supportive care is often the only intervention available while the \nbody fights off the virus. Dr. Packham observed that during her rotations, every child she saw hospitalized with a severe respiratory infection had not been vaccinated against the pathogen \ninvolved, either due to parental choice or because they were too young to qualify for \nvaccination. She highlighted the effectiveness of vaccines and RSV monoclonal antibodies in \npreventing severe illness and stated her intention to receive the RSV, flu, and COVID -19 \nvaccines during her pregnancy. She also plans to ensure her child gets all recommended \nvaccines and antibody protections when eligible. Dr. Packham concluded by stressing the \n52 \n importance of providing parents with the opportunity to discuss vaccination with their \npediatricians and that vaccines and antibodies remain accessible and covered by insurance.  \n \nDi\nana Figueroa, LVN  \nKaiser Permanente  \n \nDi\nana Figueroa, a licensed vocational nurse (LVN) with 16 years of experience, including 14 \nyears in pediatric care, provided public comment. She expressed concern over the recent termination of 17 ACIP members, describing it as a poor decision given their  extensive vetting \nand history of making evidence- based vaccine recommendations. She stated that the removal \nof these members undermines trust in the vaccine decision- making process and increases the \nrisk of health policy being influenced by unqualified individuals making decisions based on \npersonal opinions rather than scientific evidence. Ms. Figueroa also addressed shared clinical \ndecision- making, noting that it creates barriers for LVNs and LPNs like herself to administer \nrequested vaccines, ultimately delaying patient care. She emphasized that the healthcare system is already overwhelmed and that preventative care, including immunizations, is critical to \nreducing costly hospitalizations for both chronic and infectious diseases. She urged the FDA \nand CDC  not to create additional barriers to vaccine access. She emphasized the importance of \nprotecting vulnerable populations, including pregnant women, newborns, the \nimmunocompromised, the elderly, and healthy individuals who choose to be vaccinated to \nprotect  their communities. Ms. Figueroa called for the reinstatement of the previously terminated \nACIP members, the removal of recently appointed unvetted members, and the restoration of prior COVID -19 vaccine recommendations for pediatric and pregnant populations, which she \nbelieves have been effective in preventing disease.  \n \nDr\n. Amy Hardin  \nNorthside Pediatrics  \n \nD\nr. Amy Hardin, a pediatrician in private practice in Woodstock, Georgia, provided public \ncomment emphasizing the critical importance of vaccines in preventing severe childhood illnesses and deaths. She reflected on her training at Emory from 1990 to 1993,  when, before \nthe introduction of Haemophilus influenzae type B (Hib) and pneumococcal vaccines, pediatricians frequently admitted children with high fevers for complete septic workups. These included blood cultures, catheterized urine samples, and spinal taps to check for meningitis and \nsepsis. At that time, one in 200 children under five developed invasive Hib disease, resulting in \nconditions such as sepsis, epiglottitis, cellulitis, and meningitis. Many children died, while others \nwere left with lifelong  disabilities, including deafness, cerebral palsy, and severe learning \nchallenges. Dr. Hardin noted that she has not seen a single case of Hib or pneumococcal \nmeningitis or sepsis since 1999, a year she remembers vividly because it was the last time she \nattended a funeral for a child who died from a vaccine- preventable disease. She recounted the \ndeath of a two -year-old boy who missed his routine vaccination and died from pneumococcal \ninfection three months later. She expressed concern that vaccine hesitancy  and misinformation \nare causing a resurgence of vaccine- preventable diseases. Her colleagues in Atlanta are now \ntreating new cases of Hib meningitis, primarily in unvaccinated children whose parents were \ninfluenced by misinformation online. Dr. Hardin urged ACIP members to protect the health of America’s children by continuing to promote evidence- based vaccine policies. She concluded by \naffirming that vaccines are safe, effective, and lifesaving, and warned against allowing the country to return to a time when preventable childhood deaths and disabilities were common.  \n \nA\ndrianna Williams  \nPrivate Citizen  \n53 \n  \nAdr\nianna Williams, a private citizen, provided public comment expressing strong opposition to \nvaccines, including those under discussion at the meeting. She referenced the Hippocratic Oath \nand stated her belief that vaccines cause harm and should be abolis hed. Ms. Williams asserted \nthat there are safer, natural alternatives for disease prevention. She described vaccines as a bioweapon mechanism, claiming that cumulative harm results from the interaction of vaccine ingredients with bodily systems. She cited data from the Vaccine Adverse Event Reporting \nSystem (VAERS), reporting over 8,000 adverse events and more than 70 deaths following RSV \nvaccination. She specifically referenced VAERS report ID 28021 as an example of an RSV \nvaccine- related death. Ms. Williams urged ACIP members to listen to individuals who report \nvaccine injuries and called for the immediate cessation of all vaccine recommendations, \nbeginning with the RSV vaccines under consideration at this meeting. She concluded by asking \nthe committee to act following the principle of \"do no harm\" and to prioritize the health and \nsafety of both present and future generations. \n \nRosel\nie Bright, ScD  \nPrivate Citizen  \n \nDr\n. Roselie Bright, a retired epidemiologist from the FDA, expressed concern about the recent \nerosion of scientific integrity in federal health agencies. She described how, during her career, regulatory decisions were based on transparent documentation and  collaboration among \nexperts, which built trust in the process. However, she now questions federal decisions due to political interference, mass firings of scientists, and changes to the structures of advisory committees. Bright urged continued consideration of long COVID in vaccine recommendations, \nuniversal access to COVID -19 vaccines three times per year, and the development of more \neffective vaccines. She called for increased transparency in ACIP meetings, including simultaneous public access to meeting materials, more time for public comment, and \nsummaries of those comments during meetings. She also advocated reinstating the 17 removed \nACIP members, requiring scientific competency for all members, and barring anyone who \ndisregards research ethics from serving in advisory roles.  \nDue to time constraints, Dr. Kulldorff announced that the remaining RSV discussion will continue on July 26, 2025; summaries of those discussions are included in the RSV section \nabove. The meeting was then recessed until July 26, 2025, at 8:00 AM  EST.  \n \nTHURSDAY : APRIL  26, 2025 \n \nWELCOME AND I NTRODUCTIONS  \n \nC\nall to Order/Roll Call  \n \nD\nr. Martin Kulldorff, Chair of the ACIP, convened the meeting on June 26, 2025. Dr. Mina \nZadeh, ACIP Executive Secretary from the CDC, welcomed the committee, followed by a roll call from members, each of whom announced their presence. \n \nINFLUENZA  VACCINES  \n \nD\nr. Vivien Dugan (CDC/NCIRD) summarized the influenza vaccine session, which covered five \npresentations. These included data on the immunogenicity and safety of the Flublok \n54 \n recombinant influenza vaccine in older children and adolescents, updated estimates of influenza \nburden and the impact of influenza vaccination for the 2024– 2025 influenza season, an \noverview of the 2024– 2025 influenza season with proposed influenza vaccine recommendations \nfor 2025– 2026, a review of thimerosal preservative and proposed updates related to the use of \nthimerosal -containing influenza vaccines.  \nDr. Pedro Folegatti (Sanofi Pasteur) presented the results of a Phase 3 immunobridging non -\ninferiority trial evaluating the quadrivalent recombinant influenza vaccine (RIV4) , which is \nlicensed as Flublok in older children and adolescents, compared to adults. Dr. Folegatti \ndisclosed that he was a full -time employee of Sanofi and held shares in the company.  \nRecombinant protein technology has been established a proven approach to vaccine development against infectious diseases since the late 1980s, demonstrating safety and \neffectiveness across multiple pathogens, including hepatitis B, HPV, zoster, COVID -19, and \ninfluenza. For influenza vaccines, this technology offers several advantages: it maintains the \nsequence integrity of flu antigens consistent with FDA -selected strains, operates independently \nof egg supply, and does not involve culturing or handling live influenza viruses. As a result, there \nis no egg adaptation of the virus. Additionally, the recombinant influenza vaccine avoids the \ninactivation step, preserving the native hemagglutinin conformation of the wild- type virus, which \nsupports a more optimal protective immune response.  \nKey clinical evidence supporting Flublok includes several Phase 3 trials. In a randomized controlled efficacy trial among adults aged 50 and older, Flublok provided 30 to 43% greater \nprotection against biologically confirmed symptomatic influenza compared to a U.S. -licensed \nstandard -dose inactivated influenza vaccine during a predominantly H3N2 mismatch season. A \nPhase 3 immunobridging study in adults aged 18 to 49 demonstrated non -inferior immune \nresponses to three of four strains when compared to the same standard -dose vaccine. The \ntrivalent formulation of Flublok was first licensed in 2013, followed by the quadrivalent version in 2016 for individuals aged 18 and older. The label has since been updated and approved by the \nFDA to include children aged 9 and  older, based on the data presented today. As of January 31, \n2025, more than 43 million doses of Flublok have been distributed globally. The vaccine has an \nestablished safety profile and is well tolerated, with no safety signals identified to date.  \nThe study presented was part of a pediatric research plan for Flublok, developed in coordination with the FDA and international regulatory authorities. It was a Phase 3, multi -center, open- label, \nnon-randomized immunobridging study conducted at 36 sites ac ross Spain, Poland, the Czech \nRepublic, and the U.S. The trial aimed to enroll up to 1,334 healthy participants aged 9 to 49 years, all of whom received a single dose of Flublok. The primary objective was to demonstrate \nnon-inferiority of immune responses in children and adolescents (ages 9– 17) compared to \nadults, where vaccine efficacy had already been established. Immune responses were evaluated using hemagglutination inhibition antibody titers and seroconversion rates four weeks \npost-vaccination. The key  secondary objective was to assess the safety profile of Flublok by age \ngroup.  \nParticipants received their vaccination on Day 1, with a baseline blood sample collected. This \nwas followed by a safety phone call on Day 9 and a clinic visit on Day 29 for a safety review and \na second blood draw. They were monitored for six months after v accination. Solicited local and \nsystemic adverse events were collected over a seven- day period, while unsolicited and \nmedically attended events were tracked for 28 days. Serious adverse events and adverse \nevents of special interest were monitored throughout the study. Key exclusion criteria included \nreceipt of any vaccine within four weeks before or after enrollment, except for COVID -19 \nvaccines, which were allowed if administered at least two weeks apart from the study vaccine, and receipt of any influenza vaccine within the six months before enrollment. The primary \n55 \n immunogenicity endpoints were geometric mean titer (GMT) ratios and seroconversion rates at \nDay 29 for each of the four influenza strains. The study was designed with 80% power to \ndemonstrate non- inferiority based on eight tests. Non- inferiority was met if  the lower bound of \nthe 95% confidence interval for GMT ratios was greater than 0.667, and the lower bound for the \ndifference in seroconversion rates was greater than - 10%.  \nOf the 1,334 participants initially planned, 1,308 were enrolled between October 27, 2022, and \nMay 1, 2023. A total of 641 participants in the 9 to 17- year-old group and 658 participants in the \n18 to 49- year-old group received the vaccine. Among them, 626 children and adolescents, as \nwell as 634 adults, provided both pre - and post -vaccination blood samples for the primary \nendpoint. Overall, the study achieved high and comparable retention rates across both age \ngroups.  \nThe study included more females than males. The mean age was 13 years in the 9 to 17- year-\nold group and 34 years in the 18 to 49 -year-old group. Most participants were White, with Black \nor African American individuals making up nearly 19% of the total enrolled population. \nAdditionally, 87% of participants identified as non -Hispanic or Latino.  \nThe primary endpoint assessed antibody responses four weeks after vaccination, comparing the \n9 to 17- year-old group with the 18 to 49- year-old group. Geometric mean titers (GMTs) on Day \n29 were evaluated for all four influenza strains in the vaccine. The data showed that antibody \nresponses were comparable between the two groups, with children and adolescents generally \nexhibiting higher responses than adults. The GMT ratios, along with their 95% confidence \nintervals, all exceeded the non- inferiority margin o f 0.667. The lower bounds ranged from 1.09 \nfor B/Yamagata to 2.76 for H3N2, demonstrating that non- inferiority was met for all strains.  \nSeroconversion was defined as a four -fold or greater increase in antibody titers for participants \nwith a baseline hemagglutination inhibition (HAI) titer of 10 or higher, or a post -vaccination titer \nof at least 40 for those who were seronegative at baseline. The differences in seroconversion \nrates between the 9-  to 17 -year-old group and the 18-  to 49 -year-old group ranged from ( -) \n0.59% for H3N2 to 14.3% for B/Yamagata. In all cases, the lower bound of the 95% confidence interval remained above the non -inferiority margin of –10%, indicating that the primary objective \nof demonstrating non- inferior immune responses was achieved for all four influenza strains, \nbased on both Day 29 geometric mean titer ratios and seroconversion rates.  \nFor the secondary objective, 10 participants, representing less than 1% of the total enrolled \npopulation, reported at least one serious adverse event, and 5.1% reported at least one \nmedically attended adverse event. None of these events w\n…[truncated]", "summary": "MEETING OF THE ADVISORY  COMMITTEE ON IMMUNIZATION  PRACTICES (ACIP)     J UNE 25-26 , 2025  MEETING SUMMARY                                                                        Tr ade names are used for identification purposes only and do not indicate endorsement.          2   WEDNESDAY : JUNE  25, 2025    WELCOME AND I NTRODUCTIONS     C all to Order/Roll Call     D r. Martin Kulldorff, Chair of the ACIP, convened the meeting on June 25, 2025. He welcomed  the members, thanked the current…", "source_url": "https://www.cdc.gov/acip/meetings/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/minutes/summary-2025-06-25-26-508.pdf", "doc_date": "2025-06-25", "case": "acip", "sub_case": "minutes", "tags": ["acip", "cdc", "vaccines", "minutes"], "page_count": 88}
{"title": "Final posted 2025 04 11 508", "content": "Final Agenda\nDr. Keipp Talbot (ACIP Chair)\nDr. Melinda Wharton (ACIP Executive Secretary, CDC)\n8:15 Mpox Vaccine \nIntroduction\nPresentation on immunogenicity and safety of JYNNEOS in 12-17 year olds\nEtR for JYNNEOS in outbreaks and due to the 2022 global outbreakDr. Faisal Minhaj (CDC/NCEZID)\nDr. Buddy Creech (Vanderbilt University)\nDr. Faisal Minhaj (CDC/NCEZID)\n9:55 Lyme Disease Vaccine Dr. Grace Marx (CDC/NCEZID)\n10:00 Influenza Vaccines \nI\nntroduction\nInfluenza vaccine effectiveness update\nFluMist self/caregiver administrationDr. Jamie Loehr (ACIP, WG Chair)\nDr. Aaron Frutos (CDC/NCIRD)\nDr. Sophie Zhu (California DPH and CDC/PHIC), Dr. \nJoshua Quint (California DPH)\nDr. Allyn Bandell (AstraZeneca)\n11:15 Break\n11:30 COVID-19 Vaccines\nIntroduction\nModerna mRNA-1283 COVID-19 vaccine\nEpidemiology and risk factors for COVID-19 hospitalizations\nVaccine effectiveness update\nWorkgroup considerations for use of 2025-2026 COVID-19 vaccinesDr. Robert Schechter (ACIP, WG Chair)\nDr. Bishoy Rizkalla (Moderna)\nDr. Fiona Havers (CDC/NCIRD)\nDr. Ruth Link-Gelles (CDC/NCIRD)\nDr.  Lakshmi Panagiotakopoulos (CDC/NCIRD)\n1:30 Pneumococcal Vaccines\nWorkgroup Next Steps and Proposed Work Plan Dr. Miwako Kobayashi (CDC/NCIRD)\n1:45 B reak\n2:00 Human Papillomavirus (HPV) Vaccines\nIntroduction\nUpdate on literature related to reduced number of doses for HPV vaccination\nKEN SHE trial\nHPV vaccination coverage    \nModeling of reduced number of doses for HPV vaccination\nModified EtR: wording of the age for routine HPV vaccination\nWorkgroup next steps and considerationsDr. Oliver Brooks (ACIP, WG Chair)\nDr. Carla DeSisto (CDC/NCIRD)\nDr. Ruanne Barnabas (Harvard University)\nMs. Cassandra Pingali (CDC/NCIRD)\nDr. Jane Kim (Harvard University)\nDr. Ruth Stefanos (CDC/NCIRD)\nDr. Lauri Markowitz (CDC/NCIRD)\n4:00 Cytomegalovirus (CMV) Vaccines\nIntroduction\nCMV and cCMV epidemiology and disease burden\nCMV vaccine safety and immunogenicity data\nInitial workgroup considerations for CMV vaccine policyDr. Denise Jamieson (ACIP, WG Chair)\nDr. Tatiana Lanzieri  (CDC/NCIRD)\nDr. Robert Paris (Moderna)\nDr. Tatiana Lanzieri  (CDC/NCIRD)\nDr. David Sugerman (CDC/NCIRD) 5:00 U.S. Measles Update\n5:30 AdjournMEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)\nC\nenters for Disease Control and Prevention\nAtlanta, Georgia 30329  \nTuesday, April 15, 2025\n8:00 Welcome & Introductions \nFinal Agenda\nDr. Keipp Talbot (ACIP Chair)\n8:15 Meningococcal Vaccines \nIntroduction\nGSK pentavalent vaccine: update of EtR and workgroup considerations\nUpdates to Meningococcal vaccines VFC resolution\nIntroduction to MenQuadfi label change for infants\nMenQuadfi in infants: safety and immunogenicity\nWorkgroup considerations regarding MenQuadfi in infantsDr. Jamie Loehr (ACIP, WG Chair)\nDr. Sarah Schillie (CDC/NCIRD)\nDr. Jeanne Santoli (CDC/NCIRD)\nDr. Sarah Schillie (CDC/NCIRD)\nDr. Rachel Dawson (Sanofi) \nDr. Sarah Schillie (CDC/NCIRD)\n9:30 Break\n9:45 Respiratory Syncytial Virus (RSV) Vaccines - Adults\nIntroduction\nManufacturer Presentation: mRNA-1345 (Moderna) Immunogencity in Adults \n18-59 at Increased Risk; 24-Month Re-Vaccination\nManufacturer Presentation: Arexvy (GSK) 36-Month Re-Vaccination\nEconomic Analysis of Adult RSV Vaccination, including benefits and risk \ndiscussion\nComparison of Economic Analyses of Adult RSV Vaccination\nEvidence to Recommendations\nClinical ConsiderationsDr. Albert Shaw (ACIP, WG Chair)\nDr. Frances Priddy (Moderna) \nDr. Susan Gerber (GSK)\nDr. Ismael Ortega-Sanchez (CDC/NCIRD) \nDr. Ismael Ortega-Sanchez (CDC/NCIRD)\nDr. Diya Surie (CDC/NCIRD), Dr. Michael Melgar \n(CDC/NCIRD)\nDr. Diya Surie (CDC/NCIRD)\n12:15 Break\n12:30 Chikungunya Vaccines\nIn\ntroduction\nEtR for use of virus-like particle chikungunya vaccine among adolescent and \nadult travelers \nEtR for use of virus-like particle chikungunya vaccine among laboratory workers\nSurveillance for adverse events following use of live attenuated chikungunya \nvaccine and its use among travelers\nClinical guidance for use of virus-like particle chikungunya vaccine among \npregnant and breastfeeding womenDr. Edwin Asturias (ACIP/WG Chair)\nDr. Susan Hills (CDC/NCEZID)\nDr. Erin Staples (CDC/NCEZID)\nDr. Susan Hills (CDC/NCEZID),\nDr. Erin Staples (CDC/NCEZID)\nDr. Susan Hills (CDC/NCEZID), Dr. Dana Meaney-\nDelman (CDC/NCBDDD)\n3:00 Break\n3:10 Public Comment \n3:40 VOTES \nMeningococcal Vaccines\nMeningococcal Vaccines VFC\nRSV Adult \nChikungunya VaccinesDr. Sarah Schillie (CDC/NCIRD)\nDr. Jeanne Santoli (CDC/NCIRD)\nDr. Michael Melgar (CDC/NCIRD)\nDr. Susan Hills (CDC/NCEZID)\n4:10 Respiratory Syncytial Virus (RSV) Immunizations- Maternal/Pediatric \nIntroduction\nEtR: Clesrovimab\nClinical considerationsDr. Helen Chu (ACIP, WG Chair)\nMs. Danielle Moulia (CDC/NCIRD)\nDr. Jefferson Jones (CDC/NCIRD)\n5\n:10AdjournWednesday, April 16, 2025\n8:\n00\nWelcome & Introductions\nFinal Agenda\nAcronyms\ncCMV Congenital cytomegalovirus\nCDC Centers for Disease Control and Prevention\nCMV Cytomegalovirus\nCOVID-19 Coronavirus disease 2019\nDPH Department of Public Health\nEtR Evidence to Recommendations Framework\nHPV Human papillomavirus\nNCBDDD National Center on Birth Defects and Developmental Disabilities\nNCIRD National Center for Immunization & Respiratory Diseases\nNCEZID National Center for Emerging and Zoonotic Diseases \nPHIC Public Health Infrastructure Center\nRSV Respiratory Syncytial Virus \nWG Work Group\nVFC Vaccines for Children", "summary": "Final Agenda Dr. Keipp Talbot (ACIP Chair) Dr. Melinda Wharton (ACIP Executive Secretary, CDC) 8:15 Mpox Vaccine  Introduction Presentation on immunogenicity and safety of JYNNEOS in 12-17 year olds EtR for JYNNEOS in outbreaks and due to the 2022 global outbreakDr. Faisal Minhaj (CDC/NCEZID) Dr. Buddy Creech (Vanderbilt University) Dr. Faisal Minhaj (CDC/NCEZID) 9:55 Lyme Disease Vaccine Dr. Grace Marx (CDC/NCEZID) 10:00 Influenza Vaccines  I ntroduction Influenza vaccine effectiveness update…", "source_url": "https://www.cdc.gov/acip/meetings/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/agendas/Final-posted-2025-04-11-508.pdf", "doc_date": "2025-04-11", "case": "acip", "sub_case": "agendas", "tags": ["acip", "cdc", "vaccines", "agendas"], "page_count": 3}
{"title": "summary 2025 04 15 16 508", "content": "MEETING OF THE ADVISORY \nCOMMITTEE ON IMMUNIZATION \nPRACTICES (ACIP)  \nAPRIL 15-16, 202 5 \nMEETING SUMMARY  \nTrade names are used for identification purposes only and do not indicate endorseme nt. \n2 TUESDAY : APRIL 15, 2025 \nWELCOME AND INTRODUCTIONS \nCall to Order/Roll Call  \nDr. Keipp Talbot (ACIP Chair) called the April 15, 2025, Advisory Committee on Immunization \nPractices (ACIP) meeting to order.  Dr. Melinda Wharton (ACIP Executive Secretary) made \nopening announcements about the availability of presentation slides on the ACIP website, the \nscheduled oral public session, and the written public comment process  through regulations.gov  \nat Docket ID CDC -2025 -0017 . She reviewed conflict of interest (COI) policies for ACIP \nmembers. She welcomed and introduced the new committee members: Ms. Karyn Lyons and \nDr. Jane Zucker. Dr. Keipp Talbot conducted a roll call  to establish  a quorum. A list of members, \nex offici o members , and liaison representatives is included in the appendices at the end of this \nsummary document. No COIs were identified for the first day of this meeting. Dr. Chen \ndisclosed prior involvement with VLA2001 vaccine trials, noting service on data and safety \nmonitoring boards for Valneva vaccine trials that concluded in August 2024. She also co -\nauthored a paper with Valneva scientists, published in September 2024, on chikungunya \nvaccine development, and received no compensation from industry fo r that work. To avoid the \nperception of a conflict of interest related to these past activities, she will abstain from voting on \nthe chikungunya vaccine recommendations.  \nMPOX VACCINE  \nDr. Faisal Minhaj (CDC/NCEZID) provided an overview of the monkeypox virus (MPXV).  It is \nwithin the Orthopoxvirus genus and the Poxviridae family,  in the same genus that contains \nvariola virus, the causative agent of  smallpox. It was discovered in 1958 following two outbreaks \nof a pox -like disease in a research monkey colony. Although the animal reservoir is unknown, it \nis likely to be small African mammals.  The World Health Organization (WHO)  implemented the \npreferred term “mpox” for the disease in  Novembe r 2022. There are two clades of MPXV. Clade \nI is historically associated with greater disease severity in a higher proportion of people in \ncentral Africa. Clade II, which is found in West Africa, was the cause of the 2022 global \noutbreak.  \nThe first human case of mpox was identified in the Democratic Republic of the Congo (DRC)  in \n1970. In 2003, a U .S. outbreak of 47 cases occurred when small mammals from Ghana infected \npet prairie dogs. In 2017, an outbreak of 122 cases occurred in Nigeria, involving 17 states . This \noutbreak followed a period of very few reported cases for decades in Nigeria and West Africa. \nMultiple travel -associated cases followed, including 2 U .S. cases in 2021. The ongoing global \nClade II mpox  outbreak followed in 2022.  \nThe first case of the global mpox outbreak was identified in May 2022 in the United Kingdom . \nThis outbreak  primarily affected gay, bisexual, and other men who have sex with men (MSM). I t \nspreads  through  close skin -to-skin contact, including sex. Deaths have primarily occurred \namong individuals with severe immunocompromise due to advanced HIV.  The U .S. case counts \nand deaths comprise  1/3 of cases and deaths globally, with more than 30,000 cases and more \nthan 60 deaths in the U.S.  \n3 \n During the current outbreak, the peak in U .S. cases occurred in summer 2022 ; since that time, \ncases have continued to occur in the U.S . As of March 2025, cases continue to occur, with a 7 -\nday moving average in recent months ranging from  3.3 to 1.2 cases per day .  \n \nDue to the ongoing outbreak, in February 2023 , the ACIP recommended  the 2 -dose JYNNEOS® \nvaccine series for persons aged 18 years and older at risk of mpox during an mpox outbreak.   \nDose 2 is administered one month after Dose 1 .  Public health authorities determine whether \nthere is an mpox outbreak; a single case may be considered an mpox outbreak at the discretion \nof public health authorities. Other circumstances in which a public health response may be \nindicated include the ongoing risk of mpox introductio n into a community due to disease activity \nin another geographic area.    \n \nIn October 2023 ACIP made an interim recommendation for use of JYNNEOS vaccine in the \ncurrent outbreak, recommending vaccination with the 2 -dose JYNNEOS vaccine series for \npersons aged 18 years and older at risk for mpox .  Dose 2 should be administered 28 days after \nDose 1, and persons at risk include the following:  \nGay, bisexual, and other men who have sex with men (MSM), or a person who has sex with \nMSM who in the past 6 months have had one of the following:  \n• A new diagnosis of ≥ 1 sexually transmitted disease  \n• More than one sex partner  \n• Sex at a commercial sex venue  \n• Sex in association with a large public event in a geographic area where mpox \ntransmission is occurring  \nSexual partners of persons with the risks described in above  \nPersons who anticipate experiencing any of the above  \nThis is an interim recommendation which should be revisited in 2 -3 years.  \nEven a s the  global Clade II outbreak continues, there  has also been an increasing number of \ncases in the DRC  and surrounding central and east African countries , resulting in travel -\nassociated Clade I cases in multiple countries.  \nFrom June 2022 through September 2024, in the U.S. overall , JYNNEOS vaccine coverage \namong eligible individuals was 42.2% for 1  dose and 26.2% for the 2-dose  series .  Modeling \ndata suggests that any increase in coverage reduces the risk of outbreaks and that low \ncoverage (<50%) could promote larger outbreaks.  \nThe case trend for mpox cases among children and adolescents is similar to that for adults, with \nthe peak of cases occ urring  in the summer and fall of 2022 , and cases sporadically  occurring \nsince then.  \nPreviously , there w ere no data evaluating JYNNEOS  in children <18 years . An NIH -sponsored \ntrial completed last year evaluated JYNNEOS  in 12 –17-year-old adolescents.   With these  new \ndata, the work group is proposing to extend the current recommendations down to 12 -17 year -\nold adolescents.  \nProposed recommendation 1:  \nACIP recommends the 2 -dose* JYNNEOS vaccine series for persons 12 –17 years of age at risk \nof mpox during an mpox outbreak§.  \n*Dose 2 administered one month after Dose 1  \n4 \n  §Public health authorities determine whether there is an mpox outbreak; a single case may be \nconsidered an mpox outbreak at the discretion of public health authorities. Other circumstances \nin which a public health response may be indicated include ongoing risk of introduction of mpox \ninto a community due to disease activity in another geographic area.  \nProposed recommendation 2:  \nACIP recommends vaccination* with the 2 -dose† JYNNEOS vaccine series for persons aged \n12–17 years at risk for mpox §  \n* Interim recommendation to be revisited in 2 -3 years  \n† Dose 2 administered 28 days after Dose 1  \n§ Persons at risk : \n1. Gay, bisexual, and other men who have sex with men (MSM), or a person who has sex with \nMSM who in the past 6 months have had one of the following:  \n• A new diagnosis of ≥ 1 sexually transmitted disease  \n• More than one sex partner  \n• Sex at a commercial sex venue  \n• Sex in association with a large public event in a geographic area where mpox \ntransmission is occurring  \n2.  Sexual partners of persons with the risks described in above  \n3.  Persons who anticipate experiencing any of the above  \nThe Evidence to Recommendation ( EtR) frameworks  on these two proposed recommendations \nwill be presented at this meeting, with the expectation of voting at the June 2025 ACIP meeting.  \nDr. Buddy Creech (Vanderbilt) presented findings on the safety and immunogenicity of mpox \nvaccination in adolescents. He described the study as a Phase 2, randomized, open -label, \nmultisite trial (DoSES) designed to inform public health strategies for using the Modified \nVaccinia Ankara (MVA)  [Bavarian Nordic  (BN), JYNNEOS ] vaccine against mpox. Stage 1 \nevaluated the FDA -approved 2 -dose subcutaneous (SC) regimen compared to two separate \nintradermal dose -sparing regimens in adults aged 18 –50 years. Stage 2 ass essed the \nnoninferiority of the 2 -dose SC regimen in adolescents aged 12 –17 years compared to adults \naged 18 –50 years.  \nMVA -BN was administered subcutaneously on Days 1 and 29 to healthy, vaccinia -naïve \nadolescents aged 12 –17 years, compared to adults aged 18 –50. The study aimed to support \nlicensure of JYNNEOS for use in adolescents. Enrollment targeted a cohort representative of \nthe U .S. population based on 2020 Census data, intending to include  at least 25% of \nparticipants aged 12 –14 years.  \n \nThe study population included 315 adolescents aged 12 –17 years , of whom 161 were 12 -14 \nyears of age and 211 were adults. All participants received Dose 1, and nearly all received Dose \n2. Almost all  participants completed their primary endpoint evaluation at  Day 43. Solicited \nsystemic and local reactions were similar between adolescents and adults. Erythema, \ninduration, and pruritus were more comm on in both groups after Dose 2. The most common \nsystemic reactions were fatigue, headache, and myalgia, occurring at similar frequencies after \nboth doses.  \n \n5 \n The severity of solicited adverse events within 7 days of Dose 1 was 55% mild, 36% moderate, \nand 2% severe among adolescents, and 50% mild, 31% moderate, and 3% severe among \nadults. Following Dose 2, adolescents reported 36% mild, 42% moderate, and 6% seve re \nevents, while adults reported 35% mild, 37% moderate, and 19% severe events. Erythema and \ninduration were the most common severe reactions.  \n \nThe most frequent local reactions were pain at the injection site, erythema, and injection site \nnodules. Injection site nodules were reported by 117 adolescents (37%), typically appearing at \nthe beginning of the second week, and by 7 8 adults (59%). Nodule rates were similar between \nyounger and older adolescents (40% vs. 34%). Discoloration was reported by 53 adolescents \n(17%) and 38 adults (28%).  \nDizziness was reported more frequently in adolescents than in adults. No event resulted in \nsyncope  or medical attention; 7 of 8 occurred within 1 day of vaccination . Rates were similar to \nthose reported with other adolescent vaccines . Three adolescents and 4 adults received only \nthe first dose of the vaccine.  Two adolescent participants became pregnant during the study. \nChildren were born without complications or congenital anomalies.  \nImmunogenicity was assessed using a vaccinia virus (Western Reserve strain) plaque -reduction \nneutralization titer (PRNT ) assay.  Peak humoral responses ( Day 43) after a 2-dose regimen in \nadolescents were noninferior to those in adults.   Geometric mean titers at Day 43 were higher in \nadolescents than in adults, and seroconversion  at Day 43  (defined as the proportion of \nparticipants with at least a 2 -fold rise in antibody titer compared to pre -Dose 1)  was very hig h \nand similar in the two groups . \nMPXV -specific PRNT assays are still underway . Neutralization in the presence of complement \nappears more representative of in vivo neutralization ; testing of various complement sources \nhas led to the identification of critical reagents needed for neutralization across both Clade I and \nClade II MPXV .  One hundred paired samples are being tested against Clade I and Clade II \nMPXV in the presence of complement . \nLimitations included the study population being different compared to the global pediatric \npopulation at risk of mpox .  Efforts were made to ensure that the population was representative \nof the U.S. population and that the ages of v olunteers were distributed across the adolescent \nage group.  \nDr. Creech concluded that the interim data from this Phase 2 clinical trial demonstrate that the \nMVA -BN vaccine is safe and well -tolerated in adolescents aged 12 –17 years.  The peak \ngeometric mean titer ( GMT ) met prespecified noninferiority criteria for adolescents aged 12 –17 \nyears compared to adults aged 18 –50 years.  These findings are relevant to U.S. adolescents \nand areas where mpox is endemic, such as the DRC. Evaluations in younger children are \nneeded to protect  those most vulnerable, particularly given  ongoing transmission among \nchildren in the DRC and neighboring African countries . \nDr. Shaw inquired whether there was a difference in complement -mediated enhancement \nbetween adolescents and adults , and if so, whether it was due to the early or late  components \nof complement.  \nDr. Creech responded that, in general, there is no difference between adolescent and adult \nneutralization. However, differences are observed with MPXV and other viruses when \nconducting plaque reduction neutralization assays. For MPXV, complement is require d to \nneutralize both mature virions and extracellular  enveloped virions.  \n6 \n Dr. Beigel added that  the answer remains a work in progress. Assays using complement have \nbeen conducted, and increasing titers were observed. However, investigation into the underlying \nmechanisms has not yet begun. That work remains ongoing.  \nDr. Schec hter asked how soon after the immunization did dizziness occur, compared to \ndizziness and syncope with other adolescent vaccines.  \nDr. Creech shared that all events occurred within one day of vaccination, with minimal variation. \nThe characteristics were consistent with those typically seen in adolescents receiving Tdap, \nHPV, or influenza vaccines. These included transient, mild, and s elf-limited reports of \nlightheadedness that resolved quickly , reflect ing patterns commonly observed in vaccinated \nadolescents.  \nDr. Schec hter raised the question regarding reports of more severe erythema and whether \nthese correlated with discoloration or nodule formation, specifically, whether multiple \nmanifestations of local reactions tended to occur together.  \nDr. Creech shared that s evere erythema was defined as greater than 10 cm, and severe \ninduration or swelling, distinct from nodule formation, was defined as greater than 10 cm. While \nsome correlation existed between erythema and nodule formation, the association was \ninconsistent ; not all individuals with erythema developed nodules, and not all individuals with \nnodules had a history of preceding erythema. Generally, local reactions appeared around one \nweek post -vaccination. Nodules in adolescents tend to be s maller than those in adults. The \nlargest in adults measured up to 7 or 8 cm, while the largest in adolescents was 6 cm. Most \nadolescent nodules  were under 2 cm, approximately a finger's width . These reactions typically \nresolved over time, were not usually painful or distressing, and in some cases, severe erythema \nwas accompanied by pruritus at the injection site. While local reactions often clustered, they did \nnot consistently present together . However, erythema was frequently accompanied by pruritus \nand oc casionally by nodule formation.  \nDr. Faisal Minhaj (CDC/NCEZID) presented the EtR  for vaccination with JYNNEOS for \nadolescents at risk of mpox during outbreaks , focused on the question of ACIP recommending \nthe 2 -dose JYNNEOS vaccine series for persons 12 –17 years of age at risk of mpox during an \nmpox outbreak . \nRegarding the public health problem, Dr. Minhaj stated that two distinct outbreaks are occurring: \nClade I and global Clade II. The DRC is the most affected by Clade I , and other countries have \nidentified travel -associated cases . The U.S. ranks among the countries with the highest burden \nof disease due to Clade II. No week has passed without ≥1 reported case in the U.S. from May \n2022 to March 2025. Cases have been identified in both adolescent and adult populations. \nClinical manifestations of mpox can be sev ere, especially in severely immunocompromised  \npersons  in whom the infection can result in death . The work  group determined that outbreaks of \nmpox are of public health importance.  \nFor benefits and harms, Dr. Minhaj restated earlier findings on the immunogenicity and safety of \nJYNNEOS, confirming that the vaccine is safe and well tolerated in adolescents. The adolescent \narm of the study met the pre -specified criteria for noninferiori ty. Unsolicited related adverse \neffects were primarily injection site reactions. Dizziness, commonly observed in this age group , \nis unlikely to represent a safety concern after vaccine administration . CDC vaccine safety data \nsources for JYNNEOS include the  Vaccine Adverse Event Reporting System (VAERS), Vaccine \nSafety Datalink (VSD), V -safe, and single -patient Emergency Investigational New Drug (EIND) \nprocedures. From 2022 to 2023, at least 1,245 persons <18 years of age received one or more \ndoses of JYNNEOS.  No serious adverse events were identified from any of these data sources. \nThe work group  determined that the desirable anticipated effects were large, the undesirable \n7 \n anticipated effects were small, and that the desirable effects outweighed the undesirable ones , \nfavoring intervention.  \nDr. Minhaj noted that the NIH rapidly completed trial recruitment for the values domain, with \nparticipants expressing support for joining the trial to help friends. During outbreaks, pediatric \nclose contacts were vaccinated. The Adolescent Medicine Trials Network for HIV/AIDS \nInterventions (ATN) surveyed youth advisors, with 12 out of 13 respondents expressing support \nfor vaccination. It remains uncertain what type of outbreak may occur in the future or how \nadolescents would perceive their risk and the acce ptability of vaccination. The work group  \nconcluded that the target population would \"probably\" perceive the desirable effects as large \nrelative to the undesirable effects. The work group  was torn on whether there was “possibly \nimportant uncertainty or variability” and “probably no important uncertainty or variability” in how \nmuch people value the primary outcome. The nature of the outbreak may impact how \nadolescents view their risk and their likelihood of accepting  vaccination.  \nDr. Minhaj described two surveys for the acceptability domain: one administered to Adolescent \nMedicine Trials Network (ATN) providers and another to mothers of adolescents and younger \nchildren. Of the 21 surveyed ATN providers who care for at-risk adolescents, over half already \noffered the mpox vaccine. 95% reported they would recommend the vaccine for eligible patients \nand expressed no concerns. The majority noted challenges the financial cost to the clinic being \nthe most frequently cited concern. The survey of mothers of children aged ≤18 years resulted in \nindications that most mothers do not perceive their children as being at risk for mpox; however, \nthe intent to vaccinate was higher than expected.  The work group felt that the intervention \nwould “probably” be acceptable to key stakeholders.  \nFor the health equity domain, Dr. Minhaj noted that Black adolescents represent a significant \nproportion of mpox cases but a smaller proportion of vaccine uptake, reflecting known racial \ninequities. No specific groups or settings would be disadvantaged by a recommendation for \nJYNNEOS use during mpox outbreaks. Immunogenicity is consistent among immunocompetent \nindividuals aged 12 to 17 years. Vaccine implementation should ensure equitable access. \nEndorsement by ACIP could support broad acceptance of the rec ommendation through \nmechanisms such as insurance coverage, support from health departments, and availability in \npharmacies. The work group  concluded that the impact on health equity would probably \nincrease.  \nFor the feasibility domain, Dr. Minhaj explained that a wide range of vaccinators are authorized \nto administer the vaccine. Facility sites include public health departments, sexually transmitted \ninfection ( STI) clinics, adolescent health clinics, and pediatric offices. The vaccine uses the \nsame immunization information systems (IIS) and reporting infrastructure as other vaccines. \nLimitations to access include poor availability in rural communities, high vaccine cost, and the \npossibility that pediatricians m ay defer vaccination to STI or adolescent clinics. The 2 -dose \nschedule, administered 28 days apart, requires follow -up and reminders. Once thawed and \nrefrigerated, JYNNEOS remains viable for either 4 or 8 weeks, allowing time to schedule the \nsecond dose. Frozen storage is approximately 18 months. The work group  concluded that the \nintervention is “probably” feasible to implement.  \nFor the resource domain, Dr. Minhaj stated that JYNNEOS is commercially available and \nsupported by similar mechanisms for billing and reimbursement, including Medicaid, Medicare, \nand 317 funding. Vaccines are generally considered a good use of resources du ring an \noutbreak. However, the cost -effectiveness of vaccination during a future outbreak in \nadolescents remains uncertain. The work group  concluded that the intervention would \n“probably” be a reasonable and efficient allocation of resources.  \n8 \n Overall, the work group  felt that t he desirable consequences clearly outweigh the undesirable \nconsequences in most settings , concluding the EtR presentation . \nMs. Moser asked whether the proposed recommendation is to change the starting age from 18 \nto 12, or whether the recommendations would be separate.  \nDr. Minhaj responded that the recommendations would be separated, but the adolescent \nrecommendation would be aligned with the language in the adult recommendation.  \nMs. Moser inquired whether mpox data collection has been impacted due to funding and staffing \nchanges.  \nMr. Duffy shared that VAERS is still collecting reports.  \nDr. Shaw requested comments on the ongoing Clade I outbreak in the DRC. Two distinct \noutbreaks were noted: Clade IA, which is more rural and primarily affects children, with about \n60–70% of cases linked to household transmission, and Clade IB, which is more urban and \noccurs mainly among adults. Dr. Shaw asked whether this is still the case, whether there are \nany known biological reasons for the differences in transmission, and which Cl ade I subtypes \nhave been observed in the U.S.  \nDr. Minhaj commented that clade IA is predominantly seen endemically in the DRC and other \nendemic countries. In the DRC , about 50% of the population is under 15 years of age ; given \nthis, it is not surprising that many cases occur among children. Population dynamics also differ, \nwith more crowded housing and other factors that do not directly translate to the U.S. There is \nnothing specific about the virus that determines which po pulations are affected; rather, it \ndepends on the communities it enters. Clade I B is predominantly found in the eastern part of the \nDRC and has spread to other countries. It has primarily affected heterosexual sex networks and \nolder populations, including adults. Again, the networks through which the virus enters, not a \nbiological difference  in the virus, influence transmission patterns. In terms of cases in the U.S., I. \nFour cases of Clade I have been reported so far, all of which were travel -associated and \nidentified as Clade IB. Most travel -associated cases have been of Clade IB, al though a few \nClade IA cases have also been reported, including some  in other countries.  \nDr. Schec hter inquired whether data on adolescent vaccination or vaccination in younger \nchildren would likely become available in the coming months, based on its use in Africa, and \nasked Dr. Creech whether any participants had been  evaluated for symptoms of myocarditis, \ngiven the inclusion and exclusion criteria related to the condition. He inquired if myocarditis was \nassessed during the trial or if it was noted as a pertinent negative or absence.  \nDr. Minhaj noted that trials are underway to evaluate children younger than 12 years of age, and \nonce the data are available, they  will hopefully be presented.  \nDr. Creech followed up and shared that there were no symptoms that would have triggered an \nevaluation for myocarditis or pericarditis. This is consistent with existing data, which shows that \nthe vaccine does not appear to cause these conditions in teenager s. The eligibility criterion was \nincluded out of an abundance of caution.  \nMr. Duffy added that , based on CDC surveillance data, no cases of myocarditis have been  \nreported or identified in individuals under 18 years of age from any listed surveillance systems.  \nDr. Fryhofer pointed out that the website and the presentation contained differing statements \nregarding the balance of consequences.  \nDr. Minhaj clarified that there are two EtR responses, and the next. \nDr. Kurilla asked how many children aged 12 to 17 would be considered high risk under the \nrecommendation. Concerns were raised about how healthcare providers with low caseloads of \n9 \n these individuals and pharmacies in areas with low population density  would manage \nadministration. Challenges may still exist in ensuring access for at -risk individuals . \nDr. Minhaj clarified that the proposed recommendation applies to the use of JYNNEOS during \nan mpox outbreak. This is not limited to the 2022 outbreak; it could also apply to future \noutbreaks, like the 2003 incident involving infected pet prairie dogs. The recommendation allows \npublic health authorities to advise the use of JYNNEOS for adolescents deemed  to be at risk. \nThis allows the CDC  or public health authorities  to issue guidance identifying at -risk populations \nand recommending vaccination for adolescents, if appropriate. It was noted that the proposed \nquestion appears to be related to the following item for discussion.  \nDr. Minhaj then presented the evidence to support the recommendation framework for the \nroutine use of JYNNEOS vaccine for adolescents at risk of mpox during  the current outbreak  \n(proposed ACIP recommendation 2) . It was noted that globally , Clade I and Clade II outbreaks \nare currently ongoing. In the United States,  most vaccine doses were administered during the \nsummer and fall of 2022. Overall vaccine coverage among the adult population at risk is \napproximately 42% for 1 -dose and 26% for 2 -dose, which remai ns low and has not significantly \nchanged over the past year. This is important because once population immunity exceeds 50% \nfor at least 1 -dose, the likelihood of large outbreaks decreases significantly. Regardless of \nreaching the 50% threshold, any increa se in vaccine coverage is correlated with a decrease  in \ncases. The work group  determined that mpox outbreaks are of public health importance.  \nDr. Minhaj highlighted new safety and immunogenicity data for the benefits and harms domain \nfor JYNNEOS in adolescents. The adolescent arm met the prespecified criteria for non-\ninferiority and was well -tolerated  in this population. Vaccine administration data show that over \n1,200 adolescents received the vaccine nationwide, with no serious adverse events reported \nfrom any data sources. Based on these findings, the work group  determined that the desirable \nanticipated effects are “large”, while the undesirabl e effects are “small”. The work group  favored \nthe intervention.  \nDr. Minhaj noted that the NIH rapidly completed trial recruitment for the values domain, with \nparticipants expressing support for joining the trial to help friends. During outbreaks, pediatric \nclose contacts were vaccinated. The Adolescent Medicine Trials Network for HIV/AIDS \nInterventions (ATN) surveyed youth advisors, with 12 out of 13 respondents expressing support \nfor vaccination. The work group  felt that the target population “probably” felt that the desirable \neffects are large relative to the undesira ble effects. The work group  was uncertain  on whether \nthere was “possibly important uncertainty or variability” and “probably no important uncertainty \nor variability” in how much people value the main outcome, primarily due to the limited data on \nthis population.  \nFor acceptability, Dr. Minhaj re -emphasized that most mothers do not perceive their children as \nat risk for mpox; however, the intent to vaccinate was higher than expected. During the current \noutbreak, v accines were primarily administered to adolescents through public health and STI \nclinics. Of the 21 surveyed ATN providers who care for at -risk adolescents, over half already \noffered the mpox vaccine. 95% reported they would recommend the vaccine for eligi ble patients \nand expressed no concerns. The majority noted challenges with providing the vaccine, with \nfinancial cost to the clinic being the most cited concern. The work group  felt that the intervention \nwould “probably” be acceptable to key stakeholders.  \nFor the health equity domain, Dr. Minhaj reinforced that Black adolescents represent a \nsignificant proportion of mpox cases but a smaller proportion of vaccine uptake, reflecting \nknown racial inequities. No specific groups or settings would be disadvantage d by a \nrecommendation for JYNNEOS use during mpox outbreaks. Immunogenicity is consistent \namong immunocompetent individuals aged 12 to 17 years. Vaccine implementation should \n10 \n ensure equitable access. Endorsement by ACIP could support broad acceptance of the \nrecommendation through mechanisms such as insurance coverage, support from health \ndepartments, and availability in pharmacies. The work group  felt the impact on health equity \nwould be “probably increase d.” \nFor the feasibility domain, Dr. Minhaj reminded the committee  that a wide range of vaccinators \nare authorized to administer the vaccine for the feasibility domain. Facility sites include public \nhealth departments, STI clinics, adolescent health clinics, and pediatric offices. The vaccine \nuses the same IIS and reporting infrastructure as other vaccines. Limitations to access include \npoor availability in rural communities, high vaccine cost, and the possibility that pediatricians \nmay defer vaccination to STI or adolescent clinics. The 2 -dose schedule, administered 28 days \napart, requires follow -up and reminders. Once thawed and refrigerated, JYNNEOS remains \nviable for either 4 or 8 weeks, allowing time to schedule the second dose. Frozen storage is \napproximately 18 months. The work group  felt that the intervention “probably” would be feasible \nto implement.  \nFor the resource domain, Dr. Minhaj reiterated that JYNNEOS is commercially available and \nsupported by similar mechanisms for billing and reimbursement, including Medicaid, Medicare, \n317 funding,  and the Vaccines for Children ( VFC) program . Vaccines are generally considered a \ngood use of resources during an outbreak. However, the cost -effectiveness of vaccination \nduring a future outbreak in adolescents remains uncertain. The work group  concluded that the \nintervention would “probably” be a reasonable and eff icient allocation of resources.  \nThe work group  felt that overall, t he desirable consequences probably outweigh the undesirable \nconsequences in most settings due to uncertainty within the population.  \nProposed Recommendation 2:  \nACIP recommends vaccination* with the 2 -dose† JYNNEOS vaccine series for persons aged \n12–17 years at risk for mpox §  \n* Interim recommendation to be revisited in 2 -3 years  \n† Dose 2 administered 28 days after Dose 1  \n§ Persons at risk:  \n1. Gay, bisexual, and other men who have sex with men (MSM), or a person who has sex with \nMSM who in the past 6 months have had one of the following:  \n• A new diagnosis of ≥ 1 sexually transmitted disease  \n• More than one sex partner  \n• Sex at a commercial sex venue  \n• Sex in association with a large public event in a geographic area where mpox \ntransmission is occurring  \n2. Sexual partners of persons with the risks described in above  \n3. Persons who anticipate experiencing any of the above  \nDr. Loehr asked  about background data on cost -effectiveness for resource use. He expressed \nhesitanc e in making a recommendation without any sense of resource use.  \nDr. Minhaj shared that, unfortunately, the work group  did not have data on the cost -\neffectiveness of vaccination in the adolescent population.  \nDr. Loehr noted that approximately 150 adolescents were diagnosed with Mpox during the \noutbreak, but only 10 cases have been reported over the past two years. How many \nadolescents would fall into that category if this recommendation were intended for those  at risk \nis unclear. For adults, the estimated annual prevalence among MSM is about 3%, which \n11 \n translates to several hundred thousand individuals potentially at risk. However, that number is \nlikely much lower for adolescents. As a result, this recommendation could lead to vaccinating \ntens to hundreds of thousands of individuals to prevent a very sma ll number of cases. \nAdditionally, the cost of the vaccine, estimated between $200 and $300 per dose, raises \nconcerns about the scale of resource use. This was described as a potentially extraordinary \nexpenditure for a relatively small public health impact.  Dr. Loehr stated that he would like much \nmore information about resource use before voting on this recommendation.  \nDr. Brewer encouraged the work group  to align the dosing intervals, noting that \nRecommendation 1 includes a one -month interval between doses, while Recommendation 2 \nspecifies a 28 -day interval. The current adult recommendation also uses a 28 -day interval; \nalignment would help ensure consisten cy. He proposed striking the phrase 'vaccination with' \nfrom the current wording, noting that Recommendation 1 simply states 'recommend the \nvaccine.' This change would help to align the two recommendations and improve cl arity for the \ncommittee.  \nDr. Brooks requested raw numbers and population -at-risk estimates. Additionally, clarification \nwas sought on whether the goal of a routine recommendation in the U.S. is to prevent potential \noutbreaks or to protect at -risk individuals regardless of outbreak  status. Given the low number of \ncases and the rarity of severe complications, questions were raised about the justification for \nvaccinating a large population to prevent a relatively uncommon infection. While the rationale for \nvaccination during outbreaks  is evident, further insight was requested into the work group ’s \nreasoning for recommending routine vaccination now when infection is uncommon . \nDr. Minhaj noted that the recommendation to lower the age group was based on evidence that \nadolescents were at risk during the 2022 outbreak. Although current case numbers are low, a \nsignificant proportion of cases during the outbreak occurred in this popu lation. While the number \nof individuals covered by the recommendation would be small, it could still help prevent mpox \ncases  in this population , particularly with the increasing number of Clade I cases and the \npotential for importation.  \nDr. Laura  Bachman noted that estimating the exact number is challenging and requires \nextrapolation from available data, such as HIV pre-exposure prophylaxis ( PrEP ) use. For \nexample, IQVIA data from 2021 show that approximately 6,500 adolescents were prescribed \nPrEP. However, this dataset has limitations, as not all prescriptions are captured. Additionally, it \nis estimated that only 15 –20% of eligible adolescents are on PrEP. As a result, determining a \nprecise number remains difficult.  \nDr. Tracy Beth  Høeg (FDA)  thanked the presenters and highlighted concerns regarding the risk -\nbenefit balance of proposed Recommendation 2. It was noted that adolescents are at very low \nrisk for mpox, with fewer than 20 cases reported in the past year. Given the limited safety data, \nincluding the relatively small number of vaccinated adolescents and the 315 participants in the \nclinical trial, it is difficult to determine whether the benefits clearl y outweigh the potential harms. \nAdditionally, it was pointed out that the clinical trial excluded adolescents with significant heart \nor medical conditions, which providers should consider when evaluating the safety data's \napplicability to broader populations.  \nDr. Agam Rao responded that a cost -effectiveness analysis was not conducted when the \nrecommendation was made for adults. The intent was for the vote to be revisited in a few years, \nwith the understanding that a cost -effectiveness analysis could be performed at that tim e. \nAlthough fewer cases are occurring, the associated morbidity and mortality remain significant. \nThis recommendation was intended as an age extension of the existing adult recommendation. \nIt was emphasized that if these adolescent data had be en available during the adult vote, the \n12 \n recommendation would likely have included this population, as the perceived risk was \ncomparable. This clarification was provided to address questions related to the adult vote.  \n \nLYME DISEASE VACCINE \nDr. Grace Marx (CDC/NCEZID) introduced the new Lyme Disease  Vaccines  Work Group . Lyme \ndisease is the most common vector -borne disease in the U .S., with an estimated 476,000 cases \ndiagnosed and treated annually. Estimated healthcare costs for Lyme disease range from $345 \nmillion (M)  to $968 M each year.  \nLyme disease vaccines were developed in the 1990s using outer surface protein A antigens \nfrom the Borrelia burgdorferi  spirochete to prevent transmission during tick bites. LYMErixTM, \nlicensed by the FDA, was available from 1998 to 2002 but was discontinued due to low demand. \nSince then, Lyme disease has steadily increased in the U .S., with expansion outward from  high-\nincidence areas in the  Northeast, mid-Atlantic, and Midwest. New vaccines are in development, \nincluding the protein subunit vaccine candidate  VLA15, which is now in Phase 3 trials . Several \nmRNA candidates are  also in early  clinical trials.  \nThe work group 's objectives are to review Lyme disease epidemiology, risk  of Lyme disease , \nand vaccine candidate data; assess safety, immunogenicity, efficacy, and economic analyses; \ndevelop vaccination policy options  for ACIP consideration ; and identify data gaps.  \nDr. Marx will serve as the work group  lead. The work group  chair and other members will be \nannounced in the coming months. The first work group  meeting is scheduled for May 2025. \nEpidemiology, burden, and clinical manifestations of Lyme disease will be presented at the June \n2025 ACIP meeting.  \n \nINFLUENZA VACCINES  \n \nDr. Jamie Loehr , chair of the Influenza Work Group, introduced the session. Dr. Loehr shared \ninformation on  the 2025 –2026  influenza vaccine composition and highlighted the importance of \nthe update to the A(H3N2) component. Dr. Loehr shared that the group’s presentation will \ninclude interim vaccine effectiveness estimates for the 2024 -2025 season and an update on \nself- or caregiver administration of FluMist® (available for the 2025 –2026 influenza season). \nVotes on the recommendations for the 2025 -2026 season  will take place at the June 2025 ACIP \nmeeting.  \nDr. Aaron Frutos (CDC/NCIRD) provided interim estimates of 202 4–2025 seasonal influenza \nvaccine effectiveness (VE). Four networks contributed to VE estimates against laboratory -\nconfirmed influenza in children, adolescents, and adults across outpatient and inpatient settings: \nIVY (Investigating Respiratory Viruses in the Acutely Ill), NVSN (New Vaccine  Surveillance \nNetwork), US Flu VE Network, and VISION (Virtual SARS -CoV-2, Influenza, and Other \nRespiratory Viruses Network).  \nFor pediatrics , NVSN includes patients from outpatient clinics, emergency departments, urgent \ncare centers, and hospitals. The US Flu VE Network includes patients from outpatient clinics, \nemergency departments, and urgent care. VISION includes patients from emergency \ndepartments, urgent care, and hospitals. For adults , IVY includes patients admitted to the \nhospital. The networks include all ages across inpatient and outpatient settings and are \ngeographically diverse, including patients from 23 states.  \nAll network enrollees sought medical care for acute respiratory illness between fall 2024 and \nearly 2025. Each network uses a test -negative design, comparing the odds of vaccination \n13 \n among influenza -positive cases (confirmed by molecular assay) to those testing negative for \nboth influenza and SARS -CoV-2. Vaccination status was determined based on receipt of any \n2024 -2025 seasonal flu vaccine, using medical records, immunization registr ies, claims data, \nand/or self -report.  \nVE was calculated as (1 -adjusted OR) × 100%. All networks adjusted for region, age, and \ncalendar time of illness; IVY, US Flu VE, and VISION also adjusted for sex and race/ethnicity. \nVE was estimated for A(H1N1)pdm09 and A(H3N2) when data allowed. VISION did not report \nsubtype -specific VE due to limited data. Some estimates were excluded due to small sample \nsizes or non -converging models. VE for influenza B was not estimated, as it accounted for less \nthan 3% of surveillance specimens.  \nPediatric VE against any final influenza estimate ranged from 32% to 60% in outpatient settings \nand 63% to 78% in inpatient settings. Pediatric VE against influenza A(H1N1)pdm09 estimates \nranged from 53% to 72% in outpatient settings and was 63% in the inpatient setting. In the \nNVSN p ediatric VE against influenza A(H3N2) is estimated to be 42% in the outpatient setting \nand 55% in the inpatient setting.  VE against H3N2 was not significant for outpatients in the US \nFlu VE network, with a point estimate of 16% .  \nAmong adults , the estimate for VE against any influenza ranged from 3 6% to 54% in the \noutpatient setting and 41% to 55% in the inpatient setting. The estimated  VE against influenza \nA(H1N1)pdm09 among adults  was 42% in the outpatient setting and not significant with a point \nestimate of 39% in  the inpatient setting. The estimated  VE against influenza A(H3N2) among \nadults  was not significant in the outpatient setting , with a point estimate of 25% and was 51% in \nthe inpatient setting. For adults aged ≥65  years , estimated effectiveness against any influenza \nwas 51% in outpatient settings  in the VISION network and not significant with a point estimate of \n18% in the US Flu VE network,  and 38% to 57% in inpatient settings.  \nEstimates show that the 2024 –25 influenza vaccine reduced the risk of medically attended \noutpatient visits and hospitalizations for influenza among children, adolescents, and adults \nacross 23 U.S. states. VE was effective against influenza A, with variatio n by subtype and \nnetwork.   These results were published in MMWR in February 2025.  \nDr. Joshua Quint (California DPH) presented on the study of interim influenza vaccine \neffectiveness estimates a gainst laboratory -confirmed influenza  in California, October 2024 –\nJanuary 2025.  \nRecent changes in California’s reporting have expanded public health data sources, allowing VE \nanalyses across various age groups and settings using electronically reported vaccination and \ntesting records. Since  June 2023, negative influenza test results have been reportable to the \nstate’s electronic communicable disease reporting ; positive  results have been reportable since \nOctober 2019 .  These  data are submitted electronically by laboratories across the state.   All \ninfluenza vaccination records are now re portable to CAIR, the state’s immunization registry . \nAt the end of the 2023 -24 season, the California team  compared their interim VE estimates to \nthose from CDC’s other VE platforms . Despite differences in populations and systems, the \nestimates were remarkably similar. For children ages 6 months to 18 years, VE was 56%, falling \nwithin the confidence intervals  for nearly all the CDC platforms.  \nA case -control (test -negative) design was used, classifying those who tested positive for \ninfluenza as case patients. The analysis covered October 1 , 2024,  to January 31, 2025, and \nincluded California residents aged ≥6 months with a molecular or culture influenza test reported \nto the state’s electronic lab system. Participants were considered vaccinated if they had at least \none documented dose of seasonal fl u vaccine in the immunization registry ≥14 days before \ntesting. The earliest positive or negative tes t (if no positives) was used for individuals with \n14 \n multiple test results. Labs with weekly positivity rates >50% were excluded due to data quality \nconcerns, accounting for <5% of total tests. VE was calculated as (1 − adjusted OR) × 100%, \nusing a mixed -effects logistic regression model adjusted for continuous age, race/ethnicity, \ntesting week, a nd county as a random effect.  \nWeekly flu  activity in California peaked in late December with approximately 17,000 positive test \nresults and remained high through January.  In total, 85% of positive specimens were influenza \nA, and 7% were type B.  \nAmong samples tested by public health laboratories, the predominant subtypes were H3 (53%) \nand H1 (43%). Only 300 influenza B samples were lineage typed, so those results are limited. \nOnly about 5% of all tests are subtyped by public health labs, and these may overrepresent \nsevere cases.  \nOf 591,000 samples meeting eligibility criteria, 23% were positive for influenza and 77% were \nnegative. Vaccination rates were 17.6% among positive cases and 25.9% among negative \ncontrols.  \nThe median age of cases  was 30 years compared to 43 years for controls. Race distribution \nwas similar, though cases were 5 percentage points more likely to be Hispanic and 7 \npercentage points less likely to be white.  \nAdjusted VE against lab -confirmed influenza was 44.7% overall (95% CI: 43.7 to 45.6). By age \ngroup , the following estimates were calculated : 0-18 years , 50%; ages 1 9 to 49  years, 46%; \nages 50 to 64  years,  39%; and ≥65 years , 39%. VE against influenza A was 42% overall, while \nVE against type B was higher at 71%. Among subtyped cases, VE was 47.9% for H3N2 and \n49.5% for H1N1.  \nFor children ages 2 to 17  years , the estimated VE for live attenuated influenza vaccine (LAIV) \nwas 61% compared to 48% for those who received another vaccine type. These rates were \n45% and 52% in the previous season. Median ages were similar across groups.  \nCumulative VE estimates showed early -season variability with wide confidence intervals. VE \npeaked at 55% in early December before declining to about 45% by the end of the study period. \nMonthly analysis showed the highest VE in November at 56%, followed by a decrease in \nDecember and January, when confidence intervals were narrowest.  \nType -specific monthly VE remained high for influenza B at approximately 75% in December and \n70% in January, in contrast to the decreasing pattern observed for influenza A.  \nLimitations included incomplete documentation and reporting of vaccination and testing; inability \nto assess partial versus full vaccination status for children under 9 years; lack of information on \nsymptoms, test setting, and outcomes such as illness, hosp italization, or death; incomplete and \npotentially biased reporting of influenza subtypes; and lack of control for confounding factors \nsuch as health -seeking behavior and pre -existing conditions.  \nDr. Quint summarized that the data indicate that current influenza vaccines protect against \nlaboratory -confirmed influenza in individuals aged ≥6 months. VE was higher for influenza B and \namong younger age groups, but vaccination offered protection across all ages. This study also \nhighlights how expanded and improved public health data systems can be used to generate \ntimely, in -season VE estimates.  \nDr. Shaw inquired whether there is any information on VE against H3N2 in older adults.  \nDr. Quint responded that this season's CDC’s VE estimates do not yet include H3N2 -specific \ndata for older adults. However, this information is routinely estimated each year, and final \n15 \n estimates from networks that include older adult populations will be available at the end of the \nseason.  \nDr. Asturias requested data on the timing of immunization and illness to help determine whether \nthe observed decline in VE for influenza A types is related to waning immunity over time or \nspecific strain effects.  \nDr. Quint shared that the group did not include vaccination timing in the model. Still, it could be \ninferred that the decline in VE toward the end of the season is likely related to earlier \nvaccination timing.  \nDr. Zhu added that the group has a manuscript under peer review that examines explicitly \nwaning immunity and overall VE estimates. While the group has not closely analyzed waning for \nthis season yet, the trends are expected to be like those observed in pre vious seasons.  \nMs. Moser requested clarification on whether the comparison group consisted solely of \nunvaccinated children or included those who received the inactivated influenza vaccine.  \nDr. Zhu shared that for the pediatric LAIV analysis, approximately 455 children were vaccinated \nwith LAIV. The control group for this comparison consisted of unvaccinated children. A similar \ncontrol group was used for children who received non -LAIV vaccine s, meaning unvaccinated \nchildren served as the comparison group for both analyses. While the population was stratified \nby vaccine type, a similar  unvaccinated group was used as the reference for each VE \ncalculation.  \nMs. Moser inquired whether all four VE networks were still funded to collect data throughout this \nseason and next.  \nDr. Ellington confirmed that three of the four networks will continue active data collection during \nthe 2025 –2026 season. However, the IVY Network is planned to sunset and will not contribute \ndata for the next flu season.  \nDr. Cineas asked whether there was a data breakdown for VE estimates by vaccine type (for \nexample, high dose) and age group, specifically for patients ≥65  years  of age.  \nDr. Frutos shared that there is no data at this time, and Dr. Zhu also shared that the group does \nnot have those estimates available yet. However, product -specific VE was calculated for the \nprevious season, and those estimates will be available soon.  \nDr. H øeg asked whether potential bias was accounted for in the test -negative design studies \npresented , for example , based on the likelihood of seeking testing . \nDr. Frutos stated that one of the key strengths of the platforms and networks used to estimate \nvaccine effectiveness each year is that both influenza -positive and influenza -negative \nindividuals have acute respiratory illness. Since estimates are based on medically attended \ninfluenza rather than all infections, the potential bias from differ ences in testing behavior is \nconsidered minimal. The estimates are believed to be accurate.  \nDr. Kuril la inquired whether there has been any attempt or consideration to estimate VE \nstratified by whether individuals had a prior  season flu infection and/or had received a flu \nvaccine.  \nDr. Frutos responded that while the group did not account for this in the interim estimates, it is \nregularly examined and will be included in upcoming analyses.  \nDr. Allyn Bandell (AstraZeneca) shared the details of FluMist  for self- or caregiver \nadministration , which was licensed by the FDA last fall  and will be available for the upcoming \n2025 -2026 season . FluMist for self- or caregiver administration will be  available for home \n16 \n delivery. It expands access by allowing individuals or caregivers to administer it at home , with \nordering  through an online pharmacy service and using screening that aligns with that used in a \ntraditional pharmacy setting . \nFluMist builds on the growing acceptance of in -home healthcare. This flexibility can help \novercome common barriers like busy schedules. A recent modeling study by the University of \nPittsburgh found that increasing flu vaccination coverage in children ages 5 to 17  years of age  \nusing caregiver -administered FluMist could reduce symptomatic flu cases across all age groups. \nThis approach helps prevent missed school and work and may reduce the spread of flu at home \nand in schools.  \nStep-by-step instructions, developed through a human -factors usability study, ensure ease of \nuse. The online pharmacy service, FluMist Home, supports vaccine ordering, delivery, and \ndocumentation. A return shipment program is provided to guide proper dispo sal after use.  \nSeveral studies have evaluated the effectiveness, immunogenicity, reactogenicity, and safety of \nself- and caregiver -administered FluMist. A study of over 4,500 adults found no significant \ndifferences in effectiveness, immunogenicity, or adverse events betw een self -administered and \nhealthcare -administered FluMist. Reactogenicity was also comparable. A Department of \nDefense study involving more than 1,000 adults found no variation in immunogenicity by \nadministration method. Mean geometric titers for influenza  A were comparable (p = 0.43), and \nlocal/systemic reactogenicity events were similar. In a study of caregiver administration  to \nchildren aged 2. 6 to 17 years , all doses were successfully given. Adverse events were mild, and \nsome caregivers noted they would not have been able to vaccinate without the home option.  \nAstraZeneca conducted an FDA -required human factors usability study to inform the \ninstructions for use and packaging. The goal was to ensure intended users could administer \nFluMist safely and correctly, avoiding common errors like underdosing or incorrect \nadministration. Participants reflected the target population, including a mix of male and female \nparticipants, right/left handedness, a range of education al levels, and with and without \nexperience with nasal sprays. Results showed that 100% of users succes sfully administered the \nfull dose and understood the instructions.  \nThe final packaging and instructions used in the human factors study were submitted to the FDA \nin the supplemental BLA. When the FluMist package is opened, patients see a n instruction \nsheet that provides information on  storage, administration, and disposal. It guides users step -\nby-step, from inspecting the package to administering one spray per nostril, using plain \nlanguage and visuals. It also addresses common concerns like nasal dripping and includes \nguidance  on proper disposal . \nThe online pharmacy service, FluMist Home, supports patients who want to administer FluMist \nat home. It's important to note that AstraZeneca and A SPN (the pharmacy partner) are following \nstandard roles for vaccine manufacturers and pharmacies. AstraZeneca will manufacture and \nsupply the vaccine, develop educational and awareness campaigns, and provide support for \nFluMist -related questions. A SPN will manage the FluMist Home service, including eligibility \nscreening, dispensing, delivery, and pharmacist counse ling. A SPN pharmacists will also follow \nstate -specific regulations for determining patient eligibility, issuing prescriptions, and \ndocumenting FluMist administration in immunization information systems based on the shipping \naddress.  \nPersons ordering the vaccine will  receive text notifications with the delivery time; no signature is \nrequired. Inside the package is a sheet listing the contents, storage instructions, the Vaccine \nInformation Statement, and a QR code linking to how -to videos. FluMist should be refrigerated \n17 \n until use. Delivery is timed to ensure proper temperature and handling through two -day delivery \nservices. Patients will receive  texts until the vaccine administration is confirmed.  \nUpon receipt of confirmation of vaccination, vaccination data is entered into the state \nimmunization system using the same process used by  retail pharmacies. The pharmacy can \nsend records to the patient’s physician, and patients can also download their vaccination record \nfrom the portal to share with their provider. This mirrors standard retail pharmacy practices.  \nFluMist packaging includes a return shipment program for safe disposal of the used sprayer, \nwhich is considered medical waste. A prepaid, pre -labeled envelope is provided, so there is no \nneed to visit the post office. The envelope holds multiple sprayers a nd can be placed in a home \nmailbox. A medical waste company handles tracking and proper disposal.  \nDr. Asturias asked what happens if a patient experiences an adverse event at home, how it \nwould be reported, and who would be responsible for the patient.  \nDr. Bandell shared that patients can access instructions  in the package and online . If they \nexperience an adverse event, they can report it through the A SPN pharmacist by email or chat, \ndirectly to AstraZeneca, or through VAERS. This process mirrors existing practices in the retail \npharmacy setting , similar to other medications used at home.  \nDr. Cineas asked whether the usability studies included non -English speakers and inquired \nabout plans to develop materials in Spanish and other languages.  \nDr. Bandell explained that the usability study primarily included individuals whose first language \nwas English. However, Spanish -language support is planned for next season. The package \ninsert is already available in Spanish, and A SPN Pharmacy offers online and customer support \nfor Spanish speakers this year. Additional Spanish -language resources and broader language \nsupport are planned for future rollout. Other languages are to follow.  \nDr. Chen requested clarification on the recommended temperature range and the 12 -hour out -\nof-refrigerator limit.  \nDr. Bandell responded that the temperature range is the same as in clinical settings, typically \nbetween 35 and 4 5 degrees Fahrenheit. Most household refrigerators in the U.S. fall within this \nrange, and this information is clearly communicated to the consumer  multiple times.  \nDr. Zucker requested clarification on IIS reporting, specifically whether there is a step for \nattestation or verification that the vaccine was administered by the patient or caregiver after it is \nshipped to the household and before the pharmacy reports the  dose to the registry.  \nDr. Ami Patel (ASPN) responded that before reporting to the IIS, the pharmacy follows up with \nthe patient or caregiver to confirm that the vaccine was administered. The dose is not reported \nuntil confirmation is received.  \nDr. Zucker sought confirmation that, given the over 50 state immunization registries, a system \nwill be in place to report to each registry.  \nDr. Patel explained that they are contracting with a widely used reporting vendor, commonly \nutilized by retail pharmacies, to ensure nationwide connectivity and reporting to all jurisdictions. \nThey have already begun contracting with the company and buildi ng the connections, with plans \nto complete testing before September, when the first reporting is expected.  \nMs. Lyons asked whether there are any anticipated issues with state laws related to linking to \nan IIS through an online pharmacy rather than a pharmacy with a physical location in that state.  \n18 \n Dr. Patel acknowledged that some states require a physical location within the jurisdiction to \nreport to their IIS. They plan to work directly with those IIS programs to determine how best to \ncomply with local requirements.  \nMs. Lyons followed up to ask whether a mechanism was available to offer FluMist to a younger \nchild.  \nMr. Leone explained that pharmacy laws vary by state, and those differences will be integrated \ninto the system’s modeling. For example, suppose a child is under a certain age, such as under \nseven, and state law prohibits pharmacy administration for that ag e group. In that case, the \nsystem will block the request and prompt the user to seek vaccination in a traditional setting. He \nemphasized that FluMist will still be available in traditional healthcare settings, and individuals \nineligible through the service  will be encouraged to consult their pediatrician or healthcare \nprovider.  \nMs. Moser noted that compliance in the trials appeared to be strong and asked about the \nmechanisms in place for follow -up beyond text messaging. She also inquired about plans for \nhandling the return or disposal of unused vaccine, whether this is expected t o be a significant \nissue, and how it is being addressed.  \nDr. Bandell explained that the returns program was designed to be as simple and convenient as \npossible. All materials are preprinted and pre -labeled; the package can be placed directly back \nin the mailbox. Multiple sprayers can be included in the return. S he added that there is no \nexpectation that compliance with the return process will be an issue.  \nMs. Moser clarified that she was concerned about unused or unwanted vaccines.  \nDr. Patel clarified that, for safety reasons, they cannot accept returns once the product has been \ndispensed. Patients would be instructed to dispose of the unused vaccine in the same manner \nas a used dose . \nDr. Loehr asked whether it would be possible to distinguish self -administered from provider -\nadministered FluMist in immunization registries and whether there would be a clear indicator for \nthat distinction.  \nDr. Bandell confirmed that this distinction can be made and noted that the NDC numbers for \nself-administered and healthcare -administered FluMist are different. This allows immunization \nregistries to identify the method of administration through the NDC cod e. \nDr. Loehr raised the issue of handling situations when a child does not receive the full vaccine \ndose, such as when the child moves, the spray misses the nose or is accidentally sprayed on \nthe cheek. He sought clarification on how parents should manage obt aining another dose in \nthese cases.  \nDr. Patel explained that the patient or caregiver can contact the pharmacy to report what \nhappened in such situations. The pharmacy would handle the appropriate reporting to VAERS, \nwork with the patient’s insurance to obtain a second dose through available overrides and \nensure the replacement dose is spaced four weeks apart.  \nDr. Loehr commented that many individuals must provide proof of flu vaccination, and questions \noften arise about whether self -administered doses at home are sufficient. It was noted that \ndetermining the acceptability of home administration is the responsib ility of the hospital or \norganization, not the manufacturer. Suppose a hospital decides not to accept home dosing. In \nthat case, that decision lies with the institution, and it would not be reasonable to expect the \nmanufacturer to develop a system to meet the specific requirements of different organizations.  \n \n19 \n  COVID- 19 VACCINES \n \nDr. Robert Schechter (ACIP, Work Group  Chair) introduced  the COVID -19 Vaccines W ork \nGroup.  In August 2024, the Food and Drug Administration authorized and approved  the 2024 -\n2025 COVID -19 vaccines:  \n• Moderna COVID -19 vaccine* in persons ≥6 months  \n• Novavax COVID -19 vaccine** in persons ≥12 years  \n• Pfizer -BioNTech COVID -19 vaccine* in persons ≥6 months  \n*Omicron JN.1 lineage, KP.2 strain  \n**Omicron JN.1 lineage, JN.1 strain  \n \nACIP  recommen ds everyone aged ≥6 months should receive 2024 –2025 COVID -19 \nvaccination . \n• Children aged 6 months –4 years may need multiple doses of COVID -19 vaccines to be \nup to date, including at least 1 dose of 2024 –2025 COVID -19 vaccine  \n• People aged 5 –64 years should get 1 dose1 of 2024 –2025 COVID -19 vaccine  \n• People who are ≥65 years2 and people ≥6 months of age with moderate or severe \nimmunocompromise3 should receive a second dose  of 2024 –2025 COVID -19 vaccine 6 \nmonths after their first 2024 –2025 dose (minimum interval of 2 months)  \n• People with moderate  or severe immunocompromise may receive additional doses of \n2024 –2025 COVID -19 vaccines under shared clinical decision -making (minimum interval \nof 2 months)  \n1. People who are unvaccinated and receive Novavax COVID -19 vaccine for initial vaccination should receive 2 doses of \n2024 –2025 Novavax COVID -19 vaccine  \n2. People who are unvaccinated and receive Novavax COVID -19 vaccine for initial vaccination should receive 2 doses of \n2024 –2025 Novavax COVID -19 vaccine followed by a third dose of any 2024 –2025 COVID -19 vaccine dose 6 months \n(minimum interval 2 months) af ter the second dose.  \n3. If previously unvaccinated or receiving initial vaccination series, at least 2 doses of 2024 –2025 vaccine are recommended, \nand depending on vaccination history more may be needed. This additional 2024 –2025 vaccine dose is recommended 6 \nmonths (minimum i nterval 2 months) after completion of initial vaccination series.  \nFrom October 2021 to March 2025, provisional weekly COVID -19 death data reported to the \nCDC show  a consistent decline in deaths each year. In the first three years, there were typically \ntwo surges annually: a larger winter surge followed by a smaller late summer or fall surge. In \n2025, the winter surge was smaller than the summer/fall surge in 2024, indicating a potential  \nshift in the seasonal pattern.  Over the past four years, similar patterns in hospitalizations have \nemerged, with the winter peak being la rger than the late summer/fall peak, but as seen with \nCOVID -19 deaths,  the winter surge in early 2025 was smaller than the summer/fall surge in \n2024.  \nCOVID -19 illness levels have declined compared to previous years , while the 2024 -2025  \ninfluenza season was more severe than the 2023 –2024 season. As a result, estimates for \nillnesses, outpatient visits, and hospitalizations are higher for influenza than for COVID -19. \nDespite this, death estimates are similar for both diseases, reflecting a  higher likelihood of \nsevere outcomes from a case of COVID -19.  \nVaccination coverage for the 2023 –2024 and 2024 –2025 formulations remained low. By spring, \ncumulative coverage for adults aged ≥18 years  reached only about 20% in both years. This \nindicates that most  adults, including those at higher risk for severe outcomes, remain \nunimmunized.  \n20 \n The work group  has considered  risk-based and universal recommendations for the 2025 –2026 \nCOVID -19 vaccines.  In the spring, the FDA's Vaccines and Related Biological Products \nAdvisory Committee is expected to meet to discuss and recommend strain selection for the \n2025 –2026 COVID -19 vaccines. ACIP will review and vote on the recommended use at its June \nmeeting. V accine availability is anticipated in late summer or early fall.  \nDr. Bishoy Rizkalla (Moderna) provided an overview of Moderna’s next -generation  COVID -19 \nvaccine, mRNA -1283, in individuals ≥12 Years of Age . COVID -19 remains a leading cause of \nhospitalization among respiratory viruses in the U .S. Risk factors for severe COVID -19 infection \ninclude advancing age and pre -existing chronic conditions.  \n \nThe next -generation COVID -19 vaccine, mRNA -1283, is designed to offer stronger protection, \nespecially for those most at risk. Unlike current vaccines that use the full spike protein, mRNA -\n1283 targets only the N -terminal and receptor -binding domains, which  trigger strong immune \nresponses. This streamlined approach shortens the mRNA sequence and allows for a lower 10 -\nmicrogram dose , one-fifth of the original. It also positions mRNA -1283 as a strong candidate for \nfuture combination vaccines like Moderna’s inv estigational flu -COVID vaccine, mRNA -1083.  \n \nStudy 301 is a Phase 3 study assessing the safety, immunogenicity, and efficacy of mRNA -\n1283. It  is a randomized, blinded Phase 3 trial with participants aged ≥12 years. They were \nrandomly assigned to receive either mRNA -1283 or mRNA -1273 (commercially known as \nSpikevax®). Both of these vaccines  were bivalent vaccines targeting the original SARS -CoV-2 \nstrain and the Omicron BA.4/5 variants, in line with 2023 vaccine recommendations.  \n \nDemographics and baseline characteristics were balanced between groups. Half of the \nparticipants had a chronic condition linked to a higher risk of severe COVID -19 outcomes, as \ndefined by the CDC. Prior SARS -CoV-2 infection and time since the last COVID -19 vaccination \nwere also similar between groups.  \n \nSafety was monitored through a median follow -up of 8.8 months. There were no imbalances in \nadverse events between the vaccine groups. No cases of myocarditis or pericarditis were \nreported among mRNA -1283 recipients, and no safety concerns were identified.  \n \nmRNA -1283 elicited a higher antibody response at Day 29 compared to Spikevax. The highest \nBA.4/BA.5 neutralizing antibody geometric mean ratio (GMR) at Day 29 was observed in adults \naged ≥65 years. mRNA -1283 consistently produced higher antibody responses  compared to \nSpikevax  over time in this age group. Neutralizing antibody responses against Omicron \nXBB.1.5, observed in a separate study, were similar between mRNA -1283 and Spikevax.  \n \nPrespecified success criteria for relative vaccine efficacy were met , with an estimated relative \nefficacy of 9.3%  for mRNA -1283  compared to Spikevax  in preventing CDC -defined COVID -19. \nIn adults, efficacy increased with age, reaching a point estimate of 13.5% in those aged ≥65 \nyears. Among adolescents, immune responses were comparable between the two vaccines, \nsupporting similar protection, though est imates were less precise due to a smaller sample size \nand lower case numbers. Overall, efficacy findings wer e consistent with earlier immunogenicity \nresults, with adults aged ≥65 years showing the highest neutralizing antibody levels and the \ngreatest estimated efficacy. Relative vaccine efficacy was favorable for mRNA -1283 among \nindividuals with comorbidities an d in preventing severe COVID -19. \n \nDr. Rizkalla summarized that mRNA -1283 was generally well tolerated , and no safety concerns \nwere identified. The study met its primary noninferiority endpoints for immunogenicity and \n21 \n relative efficacy compared to Spikevax. Although the study was designed to demonstrate \nnoninferiority, results showed higher immune responses among older adults and a trend toward \ngreater efficacy with advancing age and among individuals with chronic conditions linked to \nsevere COVID -19. This vaccine has the  potential to reduce the COVID -19 burden, especially \namong those most vulnerable to severe outcomes . The anticipated  Prescription Drug User Fee \nAct (PDUFA ) date is by the end of May, with plans to offer mRNA -1283 for COVID -19 \nprevention this fall using an updated formulation aligned to circulating SARS -CoV-2 variants \nrecommended by the FDA.  \n \nDr. Asturias asked whether using one -fifth of the antigen dose in the new vaccine formulation \nmight be a better strategy, considering the existing natural or vaccine -induced immunity in most \nof the population. He noted that, as seen with other vaccines, bo osting with a lower dose can \nsometimes be more effective than using a traditional high dose.  \n \nDr. Rizkalla responded that it  has been well established that the receptor binding domain and \nthe N -terminal domain contain key epitopes critical for generating neutralizing antibodies and \ncell-mediated immune responses. Clinically, mRNA -1283 has shown that, even at a fraction of \nthe d ose, it can produce higher neutralization levels  compared to spike -based antigen designs. \nA broad range of clinical and nonclinical studies has evaluated this construct across multiple \nvariants, including the original SARS -CoV-2 strain, Beta, and Omicron variants such as BA.1, \nBA.4/5, XBB.1.5, as well as more recent variants like JN.1 and KP.2. Across all studies, mRNA -\n1283 consistently outperformed Spikevax  in inducing neutralizing antibodies. This strong \ncorrelation between neutralizing antibody response and protection is further supported by \nefficacy data, reinforcing mRNA -1283 as a robust vaccine design.  \n \nDr. Shaw inquired about the single fatal event reported in the Spikevax group. He also asked  \nwhether there were any imbalances in prior COVID -19 infection or vaccination history between \nthe groups, as both can affect immune responses.  \n \nDr. Rizkalla explained that they conducted sensitivity analyses to assess responses based on \nthe number of prior COVID -19 vaccine doses. These analyses looked at both immune response \nand efficacy. The findings showed that mRNA -1283 consistently induced hig her immune \nresponses compared to Spikevax, regardless of how many prior doses an individual had \nreceived. This translated into consistent efficacy results  that aligned with the primary analysis . \nThere were no fatal events in the mRNA -1283 investigational v accine group. One fatal event \noccurred in the Spikevax group involving a 77 -year-old female with a history of cardiovascular \ndisease. The death occurred suddenly within a week of vaccination. The investigator \ndetermined the event was unrelated to the vacci ne and most likely due to the individual’s \nunderlying cardiovascular condition.  \n \nDr. Cineas questioned whether the study population, which included individuals with multiple \ncomorbidities, also included immunocompromised patients.  \n \nDr. Rizkalla clarified that immunocompromised individuals were not included in the study. \nHowever, it is expected to perform at a comparable level because mRNA -1283 shares a \ncommon platform with Spikevax and shows similar immune responses . \n \nMs. Moser noted the encouraging potential for higher and more durable immune responses in \nolder adults . She asked  for comments on the similar rates of adverse events, despite the lower \ndose of the newer vaccine.  \n \n22 \n Dr. Rizkalla commented that both vaccines induce strong immune responses, so differences in \nsystemic adverse events would not necessarily be expected. He noted a trend toward fewer \nlocal reactions with mRNA -1283, which may be explained by its lower dose an d smaller \ninjection volume: 10 micrograms in 0.2 mL for mRNA -1283 compared to 50 micrograms in 0.5 \nmL for Spikevax.  \n \nDr. Kamboj asked whether there were any comparisons of T -cell responses between mRNA -\n1273 and mRNA -1283.  \n \nDr. Rizkalla responded that T -cell responses were evaluated in the Phase 2 study, comparing \nmRNA -1283 at the Phase 3 dose to mRNA -1273 (Spikevax). The findings showed comparable \nCD4 and CD8 T -cell responses between the two vaccines, with responses persisting through \nthe 366 -day duration of the study.  \n \nDr. Schechter asked whether it would be possible to get a more detailed age breakdown for \nmyocarditis risk, specifically within the 18 to 30 or 18 to 40 years age range. Referring to slide \nsix of the presentation, which grouped data for adolescents and then adults aged 18 to 64  \nyears , the request was made to see sample sizes and risk data for younger adults who may \nhave been at higher risk for myocarditis in the trial.  \n \nDr. Rizkalla noted that no myocarditis or pericarditis were observed throughout the program and \noffered to return to the work group  with a breakdown of demographics for the 18 years and older \npopulation.  \n \nDr. H øeg raised a question about how the efficacy of Spikevax was determined in the context of \na noninferiority study comparing it to mRNA -1283. Given the high level of underlying population \nimmunity from prior infection, there was interest in whether the comparis on relied on real -world \ndata, which can be affected by healthy vaccine bias, or on neutralizing antibodies, which have \nnot been clinically validated in individuals with prior infection. The question focused on how \nefficacy, particularly against out comes like hospitalization, COVID -19-related death, and long \nCOVID, was assessed for Spikevax to evaluate the relative performance of mRNA -1283.  \n \nDr. Rizkalla responded that the Phase 3 study was comparing the relative vaccine efficacy \nbetween the two arms, based on CDC -defined COVID -19. \n \nDr. H øeg asked how Moderna could determine the efficacy of mRNA -1283 if we don’t know \nwhat the efficacy of what it Is being compared to.  \n \nDr. Edwards explained that each season, as the strain composition of the Spikevax product is \nupdated, vaccine effectiveness is measured throughout that season. This process helps \nestablish and continuously update the vaccine effectiveness profile for each variant \ncomposition, including the one used in the current trial.  \n \nDr. Fiona Havers (CDC/NCIRD)  provided updates on COVID -19–associated  hospitalizations . \nThe trends described are based on data from COVID -NET, a population -based surveillance \nsystem that tracks  laboratory -confirmed COVID -19 hospitalizations. COVID -NET covers  about \n10% of the U.S. population. It includes data from over 300 hospitals in 98 counties across 13 \nstates. Hospitalizations are included if a positive SARS -CoV-2 test was reported within 14 days \nbefore or during admission, with testing based on clinical  judgment and facility policy. Basic \ndemographic data is collected for all cases, while detailed clinical data are gathered from a \nstratified random sample.  \n23 \n  \nCOVID -19 hospitalization rates have shown both winter and summer peaks, unlike RSV and \ninfluenza, which typically peak only in winter. For the 2024 –2025 season, COVID -19 \nhospitalization rates are lower than the previous season ; since the beginning of the COVID -19 \npandemic,  many hospitalizations have occurr ed outside the typical respiratory virus season. \nSince the 2021 –2022 peak, rates have declined across all age groups. Hospitalization rates \nvary by age group and virus, with the highest rates observed in infants aged <6 months and in \nolder adults . In the 2023 –2024 season, adults aged ≥75 years continued to experience the \nhighest cumulative hospit alization rates of any adult age group.  \n \nDuring the 2024 –2025 season, children and adolescents made up about 4% of COVID -19–\nassociated  hospitalizations. Pediatric hospitalization rates were highest in infants aged <6 \nmonths. Children  aged <5 years had higher influenza and COVID -19-associated  hospitalization \nrates than school -aged children and adolescents (aged 5 –17 years ). For children ≤4 years, \nCOVID -19 hospitalization rates during the 2022 –2023 and 2023 –2024 seasons were similar to \nthose for influenza. Among children aged 5 –17 years , COVID -19 hospitalization rates were \nlower than influenza during the same seasons.  Between October 2022 and April 2024, older \nchildren  hospitalized with COVID -19 were more likely to have underlying medical conditions \nthan younger age groups. About 1 in 5 hospitalized children and adolescents with COVID -19 \nwere admitted to the ICU. Fewer than 5% of eligible hospitalized children and adole scents had \nreceived the most recently recommended COVID -19 vaccination.  \n \nDr. Havers summarized that pediatric COVID -19-associated hospitalization rates are highest \namong the youngest age groups. Among school -aged children, hospitalization rates are \ngenerally higher for influenza than for COVID -19. More than half of children and adolescents \nhospitalized with COVID -19 had multiple underlying conditions, with the proportion increasing \nwith age. Additionally, most hospitalized children had not received the most recently \nrecommended COVID -19 vaccine during the 202 3–2024 seasons.  \n \nAdults aged ≥65 years account for more than two -thirds of all COVID -19–associated  \nhospitalizations among adults. Hospitalization rates increase with age, and in recent years, \nadults aged ≥65 years have consistently had higher COVID -19 hospitalization rates than those \nfor influenza. The risk of COVID –19–associated  hospitalization is also elevated among \ncommunity -dwelling adults aged ≥18 years with underlying medical conditions. About 1 in 5 \nadults hospitalized with COVID -19 were admitted to the ICU. Most adults hospitalized  during the \n2023 -2024 season had not received a COVID -19 vaccine since September 2022. Furthermore, \nas of November 30, 2024, only 30% of nursing home residents had received the 2024 –2025 \nCOVID -19 vaccine.  \n \nDr. Havers summarized that COVID -19 hospitalization rates are highest among the oldest age \ngroups, with adults aged ≥75 years accounting for about half of all adult hospitalizations. While \noverall hospitalization rates have declined over time, adults aged ≥75 years continued to have \nthe highest rates in the most recent season with complete data, surpassing all other adult age \ngroups, even compared to previous seasons. The risk of COVID -19 hospitalization also persists \nduring the summer months. Most hospital ized patients had not received the most recent \nCOVID -19 vaccine before admission. Chronic kidney disease, diabetes, and coronary artery \ndisease were associated with an increased risk of hospitalization across all adult age groups. \nThe relative risk of hosp italization among adults with vs. without select medical conditions \ngenerally declined with increasing  age for most, but not all, conditions  examined . \n \n24 \n Dr. Ruth Link -Gelles (CDC/NCIRD) shared interim estimates of the effectiveness of the 2024 –\n2025 COVID -19 vaccine . These findings reflect the added benefit of vaccination in a population \nwith widespread vaccine  and infection -induced immunity. Vaccine coverage was similar in the \n2023 -2024 and 2024 -2025 seasons for all adults but slightly higher among older adults during \nthe 2024 –2025 season. Coverage reached just under 25% for adults aged ≥18 years and \napproximately 41% to 47% for older age groups.  \n \nVE is measured by comparing the frequency of health outcomes in vaccinated versus \nunvaccinated individuals. During the monovalent COVID -19 vaccine rollout, absolute VE was \nused, focusing on differences between vaccinated and unvaccinated groups. During the  bivalent \nperiod, relative VE was used to compare outcomes between recipients of different vaccine \ntypes. For the 2024 –2025 COVID -19 vaccines, VE is measured using a combined approach, \ncomparing disease rates in those who received the 2024 –2025 vaccine to those who did not, \nregardless of prior vaccination or infection. This method is similar to how seasonal influenza VE \nis typically assessed.  \n \nThe first VE platform is the VISION Network, a multi -site system that uses electronic health \nrecords from over 300 emergency departments  and urgent care centers,  and more than 200 \nhospitals. VISION uses a test -negative design and includes eligible adults with COVID -like \nillness and a clinical test within 10 days before and 72 hours  after their healthcare visit. The \nanalysis includes adults aged ≥18 years with COVID -like illness. Cases are defined as those \nwith a positive nucleic acid amplification test ( NAAT) or antigen test for SARS -CoV-2 and no \npositive test for RSV or influenza. Controls are those with a negative N AAT test for SARS -CoV-\n2 and no positive test for influenza or RSV, depending on age. Vaccination status is determined \nusing electronic health records and state and city immunization registries.  \n \nThe second VE platform is the IVY Network, a multi -site system in 26 hospitals across 20 U.S. \nstates. Like VISION, it uses a test -negative design with active enrollment , including  patient \ninterviews and swab collection. Participants were adults aged ≥65 years hospitalized with \nCOVID -like illness. Cases had a positive NA AT or antigen test for SARS -CoV-2, while controls \ntested negative for SARS -CoV-2, influenza, and RSV by RT -PCR. Vaccination history is \ndetermined through electronic medical records, state and  local vaccine registries, and self -\nreport. Specimens are collected for central testing and sequencing.  \n \nAmong adult s, the 2024 –2025 COVID -19 vaccination provided additional protection against \nCOVID -19–associated  emergency department and urgent care visits, as well as \nhospitalizations, compared to no 2024 –2025 vaccine dose. The vaccine also offered protection \nagainst COVID -19–associated  hospitalizations among adults aged ≥65 years with \nimmunocompromising conditions.  \n \nDr. Link -Gelles reminded the committee  that VE should be interpreted as the added benefit of \n2024 –2025 vaccination in a population with high levels of infection -induced immunity, vaccine -\ninduced immunity, or both. While prior SARS -CoV-2 infection contributes to protection, that \nprotection wanes over time. Increased SARS -CoV-2 circulation in late summer 2024, just before \nthe vaccine’s approval, may have r aised population -level immunity against JN.1 -lineage strains, \npotentially resulting in lower measured VE than in a population with less recent i nfection.  \n \nQuestions and comments on Dr. Havers and Dr. Link -Gelles’s presentations were taken \ntogether  \n \n25 \n Dr. Asturias commented that he was encouraged by the increased focus on children, \nemphasizing the need to dispel the myth that young children are not at risk for severe COVID -\n19 or hospitalization. He noted that the data shows that hospitalization trends in children are not \ndecreasing. With new cohorts of unprotected infants born each year, current recommendations \nmay need to be adjusted to highlight the importance of vaccinating young children. He pointed \nout that 70% of pediatric hospitalizations occur in  children under four years of age, and half of \nthese cases involve children without underlying medical conditions. He stressed the importance \nof recognizing children as a priority group that needs stronger protection than they currently \nreceive.  \n \nDr. Loehr requested clarification on how chronic kidney disease was defined in the analysis, \nnoting its strong association with severe COVID -19. He asked whether the definition was based \non creatinine clearance and whether it included class 3 or class 4 kidney disease.  \n \nDr. Havers  clarified that the relative risk of chronic kidney disease may be slightly overestimated \nin this analysis due to the data collection methods used in the Behavioral Risk Factor \nSurveillance System (BRFSS), which relies on self -reported information. This co uld affect the \naccuracy of the denominator and potentially skew the results. While there is a real increased \nrisk associated with chronic kidney disease, comparing its magnitude to other underlying \nmedical conditions can be challenging. Chronic k idney disease is identified through medical \nchart review for COVID -NET hospitalizations , without strict diagnostic criteria, whereas BRFSS \nrelies on self -reported conditions.  \nDr. Kamboj asked whether any updated data have shown an improved uptake of additional \nCOVID -19 vaccine doses among immunocompromised patients nationwide. A second question \nfocused on slide 13, noting the limited sample size. While it was understandable tha t the data \nwere not sufficient to assess the time since vaccination, Dr. Kamboj inquired whether the \nnumber of doses was examined in any way.  \nDr. Link -Gelles responded that additional doses were examined, and overall, uptake has been \nlow within the VISION population (and nationally). Due to the timing of the analyses, few \nindividuals were eligible for a second or subsequent dose during the study  period. It was noted \nthat they will continue to monitor this throughout the rest of the year.  \nDr. H øeg commented that noting 90% of children hospitalized with COVID -19 were \nunvaccinated does not provide meaningful insight into vaccine effectiveness, given that nearly \n90% of children in the general population are also unvaccinated , most recently 87%, and 86% \nthe year before. The same consideration applies to adults. It’s important to account for the \nbaseline vaccination rate in the population when interpreting these findings.  \nDr. Havers clarified that the slide showing the vaccination status of hospitalized children was not \nintended to reflect VE. For VE data, reference was made to the approach and findings \npresented by Dr. Link -Gelles. Children were not included in those VE an alyses due to lower \nbaseline disease rates , but monitoring will continue throughout the year. Dr. Link-Gelles  added \nthat the design of VE studies allows for adjustment based on baseline vaccination coverage, \nusing the unvaccinated population as the referen ce group to compare the rate or risk of disease \nin vaccinated versus unvaccinated individuals.  \nDr. Naima Joseph (ACOG) highlighted the high rate of COVID -19 hospitalization in young \nchildren, particularly among infants aged <6 months who are not eligible for vaccination. \nPrevious CDC data have shown especially high rates in this group. Small studies have \nsuggested that boo sting during pregnancy may help protect these infants through maternal \n26 \n immunization. Dr. Joseph expressed interest in seeing further data on the effectiveness of this \napproach.  \nDr. Havers emphasized that the presentation primarily focused on children and infants older \nthan six months. However, it is correct that for pediatric age groups, hospitalization rates are \nhighest among infants aged <6 months, who rely on maternal vaccination during pregnancy for \nprotection. Dr. Havers acknowledged this as an important point not previously highlighted in the \ndiscussion.  \nDr. Lakshmi Panagiotakopoulos (CDC/NCIRD) shared the work  group’s considerations for the \n2025 –2026 COVID -19 vaccines. These include whether to maintain the current multi -dose initial \nseries for children aged <5 years and for immunocompromised individuals, and whether to \ncontinue a universal recommendation for eve ryone aged ≥6 months or move to a risk -based or \nhybrid approach. The group is also evaluating guidance for those recommended to receive \nmore than one dose per year, including adults aged ≥65 years a nd people aged ≥6 months  who \nare immunocompromised.  \n \nThe CDC’s list of conditions that increase the risk of severe COVID -19 is extensive and largely \nbased on pre -Omicron  data. Researchers used multiple data sources and regression modeling \nto estimate how many U.S. adults have the conditions on this list.  The analysis found that risk of \nhaving any condition increases with age, and about 74% of adults aged ≥18 years or older have \nat least one high -risk condition. Of note, s ome conditions  from the list , such as Parkinson’s \ndisease, physical inactivity, and stero id use, were not included  in the analysis, so the actual \npercentage is likely higher.  \n \nAs of the 2024 –2025 season, JN.1-lineage strains remain  the predominant circulating variants \nof SARS -CoV-2. COVID -19 hospitalization and death rates have declined overall, though rates \nremain highest among adults aged ≥65 years. Pediatric COVID -19 hospitalizations were lower \nthan those for influenza and RSV du ring the 2024 –2025 season and lower than the previous \nyear. COVID -19 also dropped in rank as a leading cause of death , from 8th to 12th in children \nbetween 2021 and 2023  and from 3rd to 10th in adults between 2021 and 2023. During the \nperiod September 2023 through August 2024, almost 90% of the deaths due to COVID -19 in the \nU.S. were among adults aged 65 years and older.  Among children under 1 year, COVID -19 \ncaused more deaths than influenza, while for those aged 1 –17 years , influenza led to more \ndeaths. Vaccine coverage remained stable, with a slight increase among adults aged ≥65  years , \nand vaccine effectiveness in adults held steady  between 2023 –2024 and 2024 –2025 . \nCumulative hospitalization rates continue to decline  since 2021 . By the end of 2022, \napproximately 90% of children aged ≥2 years , 82% of children aged 1 -2 years,  and 64% of \ninfants under 1 year of age had been infected with SARS -CoV-2. Looking at U.S. blood donors, \nhigher exposure through infection and vaccination led to increased SARS -CoV-2 antibody \nlevels, though gains diminished after 4 or more  exposures. In 2023, an estimated 9.2 million \nadults and 0.3 million children in the U.S. reported  having had  long COVID. Vaccination reduced \nthe risk of long COVID by up to 72% in children and up to 63% in adults, depending on \nsymptom type. The incidence of multisystem inflammatory syndrome in children ( MIS-C) fell \nsignificantly, from 6.8 to 0.08 cases per 1 million person -years between the pre -Delta period and \n2024. Although most children with MIS -C in 2023 and 2024 were vaccine -eligible, few were \nvaccinated, and most had received their last dose more than 12 months before illness onset.  \n \nAn increased risk of myocarditis was observed following COVID -19 vaccines during 2020 –2022, \nparticularly after the primary series and first booster doses. No increased risk has been detected \nin the VSD or in VAERS  during the 2022 –2023, 2023 –2024, or 2024 –2025 seasons to date. \nMyocarditis following COVID -19 vaccination typically resolves quickly, and cases are associated \n27 \n with less severe cardiovascular outcomes compared to myocarditis following COVID -19 \ninfection or conventional myocarditis.  \n \nThe work  group discussed concerns that shifting from a universal to a risk -based COVID -19 \nvaccine recommendation could reduce coverage among people with high -risk conditions. \nInfluenza vaccination coverage among adults with high -risk conditions increased slightly a fter \nthe universal recommendation in the 2010 –2011 season, though the trend was already rising \nand plateaued shortly afterward. Hepatitis B vaccination coverage among adults with risk factors \nremained below pre -pandemic levels following the univer sal recommendation in 2022. By 2023, \ncoverage for adults universally recommended for zoster vaccination was approaching that of \npneumococcal vaccination among high -risk adults, despite longstanding recommendations for \npneumococcal vaccination. It remains u nclear how shifting from a universal to a risk -based \nrecommendation would impact COVID -19 vaccine coverage.  \n \nThe work  group reviewed parental vaccine confidence data to better understand barriers to \nCOVID -19 vaccine uptake among children, given that vaccination rates for children aged 6 \nmonths to 17 years remain low , at around 12%, similar to last year. Only 22% of parents said \nthey were very likely to vaccinate their child against COVID -19 to prevent respiratory illness, \nwhich was lower than other prevention options  offered in the survey . Among parents whose \nchildren had previously received one dose of the COVID -19 vaccine, most maintained the same \nconfidence level  in the vaccine’s safety and effectiveness, though 15% reported less \nconfidence. In contrast, a bout 45% of parents whose children had never received a COVID -19 \nvaccine reported decreased confidence in vaccine safety and effectiveness  compared to when \nthe vaccines first became available. Parents of children who received at least one COVID -19 \nvaccine dose were more likely to have already received or plan to receive the 2024 –2025 \nvaccine for their child than  those whose children had never been vaccinated. When asked why \nthey did not vaccinate their child, parents of never vaccinated children were more likely to cite \nconcerns about safety, effectiveness, and potential side effects. Additionally, 15% of parents \nwhose children had received a prior dose believed their child had already received enough \nCOVID -19 vaccine doses.  \n \nThe work  group reviewed COVID -19 booster recommendations from other countries for \nindividuals who have completed an initial vaccine series. Most countries recommend boosters \nfor older adults every 6 to 12 months , with age cutoffs ranging from 50 to 80 years. For \notherwise healthy adults, the U .S. is the only country with a routine recommendation; other \ncountries either have no recommendation, discretionary recommendations , or recommendations \nbased on pregnancy status. Most countries recommend yearly vaccina tion for high -risk adults. \nFor immunocompromised adults, most countries recommend vaccination every 6 to 12 months, \nwith the U.S. being the only country that permits additional doses beyond two per year. Routine \nvaccination of healthy children is not widely recommended outside the U.S. and Canada \n(Canada has a discretionary recommendation in this group) . The UK, Canada, and the U.S. \nrecommend annual vaccination for high -risk children , while Australia and the WHO do not. For \nimmunocompromised children, most countries recommend vaccination every six months , with \nthe U.S. being the only country that permits additional doses beyond two per year . \n \nAs of February 13, 2025, after reviewing updated data on hospitalization risks, mortality trends, \nvaccine coverage, hesitancy, and myocarditis, the majority of the work  group supported a risk -\nbased recommendation for 2025 –2026 COVID -19 vaccination. Most members who favored a \nnon-universal policy supported a risk -based approach by conditions and exposures, a universal \nrecommendation for certain age groups, and permissive l anguage to allow anyone seeking \nprotection to receive the vaccine. Additional data on v accine effectiveness, seroprevalence, long \n28 \n COVID, vaccine coverage, and MIS -C were presented, and the group received feedback from \nliaison organizations. These organizations raised concerns about implementation, \ncommunication, confidence, and equit able access  under a risk -based recommendation. After a \nfollow -up poll on April 3, the majority still supported a risk -based approach. Most members \nselecting a non -universal policy again supported risk -based recommendations by condition or \nexposure, universal recommen dations for certain age groups, and perm issive access for those \nseeking vaccination.  \n \nDr. Jamieson expressed concern about moving to a risk-based COVID -19 vaccine \nrecommendation, noting that 74% of adults have risk factors and that COVID -19 remains a \nleading cause of death among both adults and children. There was skepticism about the \neffectiveness of risk -based strategies in the US, and hepatitis B was viewed as an unsuitable \ncomparison. Instead, influenza was seen as a more relevant example, with concern that \ndecoupling flu and COVID -19 vaccinations could create confusion as people are just beginning \nto understand the importance of recei ving both annually. Additional concerns included \nchallenges with implementing a permissive recommendation, particularly regarding healthcare \nfinancing and access. Based on the information presented, support was expressed for \nmaintaining a universal recomme ndation.  \n \nDr. Loehr expressed support for considering a risk -based COVID -19 vaccine recommendation \nand appreciated that it is being taken seriously. Concerns were raised about the data showing \nthat over 70% of adults aged 18 to 50 years are considered at risk, which did not align with \nclinical experience. The estimate seemed reasonable for older adults but appeared too high for \nthose under 50  years of age . While in favor of the risk -based approach, there was concern \nabout its feasibility and the message it may send, especially given that COVID -19 remains a \nsignificant public health issue with thousands of hospitalizations and deaths.  \n \nDr. Asturias emphasized the importance of identifying data that could help protect young infants \nand children from COVID -19, noting that this group has not received adequate attention. \nUpdated information on the transfer of maternal antibodies was highlighted as particularly \nuseful, as most existing data come from earlier in the pandemic when protection was less \ncertain. With many women now  vaccinated or previously infected, current data on maternal \nantibody transfer would be valuable. Additional details on hospitalizations among children in \ntheir first year of life were requested , particularly the causes. Based on influenza data showing \nthat young children are often hospitalized for fever and irritability, it would be interesting to see \nthe causes of these hospitalizations.  \n \nDr. Brooks emphasized the need for additional data, specifically requesting modeling on long \nCOVID. While COVID -19 rates may be low among healthy individuals in their 30s, the potential \nfor developing long COVID remains a concern. Even with a lower risk of long COVID , the \nabsolute number of cases could still be significant. The primary concern was the long -term \nimpact of long COVID, especially in younger age groups that may not receive a vaccination \nrecommendation. Modeling the absolute number of long COVID  cases in these groups was \nidentified as an important data need.  \n \nDr. Brewer addressed concerns about implementing a risk -based COVID -19 vaccine approach, \nnoting that while it's commonly believed  that such strategies are less effective, there is no clear \nevidence to support that conclusion. Although the idea has been discussed for years and \nshared by various groups, the data does not definitively show that risk -based approaches are \nless effective than universal ones. Based on the information reviewed, there was a shift in \n29 \n perspective, with the view that the belief in the limitations of risk -based strategies is not currently \nsupported by strong evidence.  \n \nMs. Moser expressed support for exploring a risk -based COVID -19 vaccine recommendation \nand emphasized the importance of including the youngest children in those considerations. \nEchoing a previous point, it was noted that young children represent a newly su sceptible group \neach year . Vaccinating  them could help reduce hospitalization rates for those under one year \nold and potentially protect them from long COVID on their first exposure. While evidence on \nlong COVID in this age group is still developing, early  vaccination may also help avoid concerns \npreviously associated with vaccinating adolescents, such as myocarditis. In a separate \ncomment, appreciation was expressed for the public comments  submitted for the meeting, \nparticularly regarding the change in licensure  status for Novavax  that was anticipated to happen \na few weeks ago . While acknowledging that this issue falls under FDA jurisdiction and not the \ncommittee’s, a request was made for an update from the FDA ex officio  to address public \ninterest, given that the  topic was not listed on the current agenda.  \n \nDr. H øeg responded that while it is unclear to what extent an update can be provided at this \ntime, a public update on the matter will be released very soon.  \n \nDr. Fryhofer shared a perspective as a practicing internal medicine physician who sees many \nolder and medically fragile patients  and expressed concern for very young children as a new \ngrandparent. Reflecting on the data showing that 74% of individuals have at least one risk \nfactor, the point was made that, in practice, simplicity is key. The \"keep it simple\" approach was \nemphasized, pa rticularly given that most adult vaccinations are administered in pharmacies. \nRisk-based recommendations can be challenging in these settings as they often require patients \nto self -report medical conditions or pharmacists to review medication histories, which some \npatients may be uncomfortable with. As a member of the COVID -19 vaccine work  group and \none of the 19% who supported a universal recommendation, Dr. Fryhofer explained that these \nconcerns contributed to that position.  \n \nDr. Loehr responded to a previous comment by referencing data from the pneumococcal \nvaccine work group , noting that uptake for the risk -based recommendation in adults aged 50 to \n65 years was around 20%, compared to approximately 65% for the age -based recommendation \nin those aged 65 years and older. This was presented as evidence that risk -based \nrecommendations may result in lower vaccine uptake. While still supportive of a risk -based \napproach, it was emphasized that this difference in coverage should be con sidered.  \n \nPNEUMOCOCCAL VACCINES \n \nDr. Miwako Kobayashi (CDC/NCIRD) shared the proposed plan on behalf of the Pneumococcal \nVaccines Work  Group. The group's term of reference is to review evidence to inform the use of \nnew pneumococcal conjugate vaccines in U .S. adults and children.  \n \nOver the past 40 years, the U .S. pneumococcal vaccine program has undergone multiple \nupdates, with several occurring in the last five years. During this period, three new \npneumococcal conjugate vaccines were licensed for use. The most recent was the 21 -valent \npneumococcal conjugate vaccine (PCV21) for adults, which was licensed last year.  \n \nThe work group acknowledges gaps  in current pneumococcal vaccine recommendations for \npregnant women. This gap is highlighted in the adult immunization schedule, which shows there \n30 \n is currently no guidance for using  pneumococcal vaccines in pregnant women  with underlying \nconditions or risk factors that increase the risk of pneumococcal disease.  \n \nAdditionally, ACIP has never specifically voted on pneumococcal vaccine use among \nhematopoietic stem cell transplant recipients. Clinical guidance for pneumococcal vaccine use \nwas last updated in 2023 following the licensure of 15-valent pneumococcal conjugate vaccine \n(PCV15 ) and 20-valent pneumococcal conjugate vaccine ( PCV20 ). Currently, there is no \nguidance on using  PCV21 for this group.  \n \nSince a formal literature review on pneumococcal vaccine use in pregnant women and \nhematopoietic stem cell transplant recipients has not been presented to ACIP, the work  group \nhas been conducting such a review. A summary of the findings and proposed language for \nupdated clinical guidance will be presented for the committee’s review and feedback at the June \n2025 ACIP meeting.  \n \nHUMAN PAPILLOMAVIRUS (HPV ) VACCINES  \n \nDr. Oliver Brooks (ACIP, Work Group  Chair)  introduced the Human Papillomavirus (HPV) \nVaccines Work Group. HPV causes cancers of the cervix, vagina, vulva, penis, anus, and \noropharynx. The HPV vaccine offers long -lasting protection against the types most likely to \ncause cancer. In the 19 years since its introduction, the vaccine has shown high efficacy in \nclinical trials , high population impact in real -world settings, and stro ng herd effects of \nvaccination programs.  \nThe HPV Vaccine s Work Group, previously active for many years, had been inactive since \n2019. It was re constituted  and began meeting monthly in July 2024. The group gave its \nreturning presentation to ACIP at the October 2024 meeting.   \nIn the U.S., HPV vaccination recommendations include routine, catch -up, and shared clinical \ndecision -making.  \n• Routine vaccination is recommended at ages 11 –12 years  and can start at age  9 years . \n• Catch -up vaccination is recommended through age 26 years for those not adequately \nvaccinated earlier.  \n• Shared clinical decision -making is recommended for adults aged 27 –45 years who are not \nvaccinated.  \nThe number of HPV vaccine doses depends on the age at which  the series is started:  \n• 2 doses are recommended if the series begins before the 15th birthday.  \n• 3 doses are recommended if the series begins at age 15 years or older, or for individuals \nwith immunocompromising conditions.  \nThe work  group is reviewing two policy issues. The first is the wording of the recommended age \nfor routine HPV vaccination. Some stakeholders support starting at age 9  years , which aligns \nwith current ACIP recommendations.  The work  group is also reviewing the recommended \nnumber of HPV vaccine doses in light of growing evidence supporting fewer doses. It is \nevaluating data on 2 doses for individuals aged ≥15 years and 1 dose for individuals aged ≥9 \nyears.  \nIn 2022, the World Health Organization recommended a 2 -dose HPV vaccination schedule for \nindividuals aged ≥9  years , with a 1 -dose option for those aged 9 –20 years . Although low - and \nmiddle -income countries were expected to adopt the 1 -dose schedule first, early adopters \nincluded the UK and Australia. Some countries did not move to a 1 -dose schedule but shifted \n31 \n from 3 to 2 doses for individuals aged >14  years . Regional advisory groups including those in \nPAHO and the WHO African Region support the 1 -dose recommendation. As of April 2025, 67 \ncountries have adopted a 1 -dose schedule for some age groups, and 77 countries have \nadopted a 2 -dose schedule.  \nDr. Carla DeSisto (CDC/NCIRD) began with an overview of the work group’s policy questions:  \n• Should 1 dose of HPV vaccine be used for prevention of HPV infection and HPV attributable \ndisease, instead of the currently recommended vaccination schedule?*  \n• Should 2 doses of HPV vaccine be used for prevention of HPV infection and HPV \nattributable disease, instead of the currently recommended vaccination schedule?† \n*There are two populations under review for this question. For individuals aged 9 –14 years, the \ncomparison is 1 dose versus the currently recommended 2 doses. For those aged ≥15 years, the \ncomparison is 1 dose versus the currently recommended 3 doses.  \n†The population for with question i s persons aged ≥15 years , and the comparison is 2 doses versus the \ncurrently recommended 3 doses.  \nThere is no plan to change the recommendation of shared clinical decision -making for persons \naged 27 -45 years, although the number of recommended doses in this age group may change.  \nThe four critical outcomes are HPV-associated cancers, precancers, serious adverse events \nrelated to vaccination, and incident persistent HPV infection.  The six important outcomes are \nprevalent HPV infection, incident HPV infection, immunogenicity, anogenital warts, low -grade \nhistological abnormalities, and recurrent respiratory papillomatosis.  \nFor the systematic literature review , Cochrane reviewed global literature on reduced -dose HPV \nvaccination schedules in 2022. This review was adapted to the U.S. context, and the literature \nsearch was updated to include publications from 2022 to 2024.  The literature review included 37 \npublications, which represent 16 studies. These publications include recently published updates \nfrom the Costa Rica Vaccine Trial (CVT), the IARC -India trial, and the Dose Reduction \nImmunobridging & Safety Study (DoRIS).  \nIn the Costa Rica Vaccine Trial (CVT), women aged 18 –25 years were randomly assigned to \nreceive 3 doses of either the bivalent HPV vaccine or a control  vaccine . Some received fewer \ndoses due to factors like pregnancy or missed visits, with reasons balanced across groups. The \ndata are being evaluated as a cohort study by the number of doses received. At the October  \nACIP  meeting, data on protection against prevalent infection and immunogenicity through year \n11 were reviewed.  Sixteen years after vaccination, H PV 16/18 seropositivity remained very high \nat >98%  in both the 1 -dose  and the 3 -dose groups ; as expected the geometric mean antibody \nconcentratio n was lower in the 1-dose group . During years 11 –16 post -vaccination, small but \nstatistically significant declines in antibody levels were observed in women who received either \n1 or 3 doses.  \nIn the IARC -India trial, unmarried girls aged 10 –18 were randomly assigned to receive either 2 \nor 3 doses of the quadrivalent HPV vaccine. A ministerial decree halting vaccination in trials \nresulted in cohorts receiving 1, 2, or 3 doses. Cervical screening with an HPV test began at age \n25 for married participants, and age - and site -matched unvaccinated married women were \nrecruited as controls. At the October  ACIP  meeting, data on protection against persistent \ninfection through 10 years were reviewed.  In their November 2024 publication, the authors \nreporte d a median follow -up time of 12 years and a total study duration of 15 years, with \nparticipants aged 25 to 33 years. VE against persistent HPV 16/18 infection was 92% with 1 \ndose, 94.8% with 2 doses, and 95.3% with 3 doses. Confidence intervals for these e stimates \noverlapped. No CIN2+ cases associated with HPV 16/18 were detected among vaccinated \n32 \n participants, compared to eight cases among unvaccinated women. No cases of invasive \ncervical cancer related to HPV 16/18 were reported in the study.  \nIn the DoRIS trial from Tanzania, girls aged 9 –14 were randomly assigned to receive 1, 2, or 3 \ndoses of either the  bivalent  or 9-valent  HPV vaccine. All participants were followed for 36 \nmonths, and those in the 1 - and 2 -dose groups were invited to join a long -term extension. The \nprimary outcome was to assess noninferiority of HPV 16/18 -specific seropositivity after 1 dose \ncompared with 2  or 3 doses of the same vaccine. The trial also included a co -primary \nimmunobridging objective to demonstrate noninferior ity of HPV 16/18 antibody geometric mean \nconcentrations  (GMCs ) after 1 dose, compared with that seen following 1 dose in efficacy \nstudies. At the October ACIP meeting, data on immunogenicity and immunobridging to KEN \nSHE through two years were reviewed . The update focused on the 9-valent HPV  vaccine, which \nis the vaccine currently used in the United States. For HPV 16, 100% of girls in both the 1 -dose \nand 2 -dose groups were seropositive  five years after vaccination . For HPV 18, 93% were \nseropositive in the 1-dose group and 98% in the 2 -dose group. Although seropositivity was high, \nnoninferiority for HPV 18 was not met.  Regarding GMCs, the 1 -dose titers were lower than the \n2-dose titers, as expected. In the 1 -dose group, titers plateaued at month 12 and remained \nrelatively stable through month 60. In the 2 -dose group, titers declined after peaking at month 7.  \nOf the 59 studies identified by the Cochrane  literature review , 49 were excluded due to a \nserious risk of bias. All excluded studies were observational. Key biases included differences in \ninfection risk at vaccination, differences in HPV exposure during follow -up, and dose timing. \nThese biases likely result in lower effectiveness with fewer doses. To address bias, researchers \nused buffer periods, stratifying results by age at vaccination or restricting the population to \nyounger ages , adjustments for sexual activity and sociodemographic factor s, and stratifying \nresults for 2 doses by the interval between first and second doses.  \nOnly one observational study with less than serious risk of bias , which provided data on a \ncritical outcome,  was identified  in the updated systematic review . The Wu -Sweden study \nfollowed 2.2 million females aged 10 –35 years  from 2006 to 2022. Using linked registries, \nCIN2+ outcomes were assessed by  the number of 4-valent HPV vaccine doses  received . \nAdjusted Poisson models with a 12 -month buffer were used, with median follow -up times of 8.4 \nyears (unvaccinated) and 12.4 years (vaccinated).  Among girls who in itiated vaccination before \nage 15, the authors observed incidence rate ratios ( IRRs ) of 0.42 after 1 dose, 0.54 after 2 \ndoses, and 0.50 after 3 doses. The overlapping confidence intervals suggest no significant \ndifference in CIN2+ risk by number of doses.  In women who initiated vaccination after age 21  \nyears , only those who received 3 doses had a statistically significant IRR. While the comparison \nwas to unvaccinated females and does not directly align with  the work  group’s policy questions , \nthe study provi des a useful example of observational data on effectiveness by number of doses.  \nThere are several outstanding questions for reduced number of HPV vaccine doses. The \nlongest efficacy data came from the IARC -India study (15 years post -vaccination), and the \nlongest immunogenicity data came  from the Costa Rica trial (16 years). No data exist on \nprotection at sites other than the cervix. Of the 16 studies, 13 included only females. There are \nno efficacy data on males for reduced -dose schedules, and some evidence suggests lower \nantibody titers in adolescent males compared with females after one dose. Data are also very \nlimited for immunocompromised individuals , and l imited data exist on efficacy and \nimmunogenicity in older age groups . \nDr. Ruanne Barnabas (Harvard University) shared the results for the KEN SHE trial. The study \nfound that the single -dose HPV vaccination is highly efficacious, with 98% vaccine efficacy for \nHPV 16/18. Results are broken into 36 -month and 54 -month periods .  \n33 \n The 36 -month results come from the randomized phase of the study, which included a control \ngroup. Women aged 15 –20 years were recruited from three clinical trial sites in Kenya and \nrandomly assigned to one of three groups: immediate 9-valent HPV vaccination ; immediate \nbivalent HPV vaccination ; or a control group receiving meningococcal vaccination.  The study \nendpoint was incident persistent vaccine  type-specific infection among HPV-naïve participants  \nat vaccination. This is important, as HPV vaccines have n o therapeutic effect.   \nParticipants were followed for 36 months. For the per -protocol analysis, those with evidence of \ninfection at enrollment or month 3 were excluded to allow for a buffer period. Cervical swabs for \nHPV DNA were collected every six months to assess persistent i nfection.  Participants with \nprevalent HPV infection at enrollment were excluded from the per-protocol /modified intention -to-\ntreat analysis, because the vaccine is prophylactic only.  \nAfter three years, single -dose HPV vaccine efficacy remained high and durable (VE  98% for \nHPV 16/18 and VE  96% for HPV 16/18/31/33/45/52/58). Based on sustained antibody levels \nover 16 years, the group hypothesized that single -dose vaccination would be effective and \ndurable over 54 months . \nAt month 36, participants in the KEN SHE study were crossed over while maintaining the study \nblind to assess the durability of HPV vaccination. Those who  had initially received the HPV \nvaccine were given meningococcal vaccination, while those who had received meningococcal \nvaccine were crossed over to receive the 9-valent HPV vaccine.  \nTo evaluate the effectiveness of single -dose HPV vaccination among individuals aged 18 –23 \nyears , researchers compared the cumulative incidence of persistent HPV infection using \nKaplan -Meier curves and incidence rate estimates for the immediate and delayed vaccine \ngroups. Vaccine efficacy was analyzed as a function of time since vaccination using a Cox \nregression model that accounted for time and time -varying covariates to assess durability . The \nprimary endpoint was incident persistent vaccine -type specific HPV infection, measured at two \ntime points six months apart.  \nThere were no differences in baseline characteristics between study groups. At cross -over \nvaccination, participants were 18 –23 years old. Retention was 90% for three or more swabs,  \nand the median time between endpoint swab collection was 6.00 months. HPV exposure to non -\nvaccine types was consistent across the study and all groups. Therefore, the only difference \nbetween the three groups was the vaccine received at randomization.  \nParticipants vaccinated with the bival ent vaccine at age 18 –23 years had similarly low rates of \nincident persistent HPV 16/18 infection compared to vaccination at age 15 –20 years. HPV 16/18 \nvaccine efficacy, VE  99.2% (95% CI 96.1 -99.9%), was sustained over time without evidence for \nwaning immunity. Participants vaccinated with the 9 -valent vaccine at age 18 –23 years had \nsimilar rates of incident persistent HPV 16/18/31/33/45/52/58 infection compared to vaccination \nat age 15 –20 years. HPV 16/18/31/33/45/52/58 vaccine efficacy, VE  98.9% (95% CI 94.9 -\n99.8%) , was sustained over time without evidence for waning immunity.  \nDr. Barnabas summarized that s ingle -dose HPV vaccination effectively protected adolescent \ngirls and young women from incident persistent HPV infection over the first 54 months post -\nvaccination. The study’s rigorous design, high protocol adherence, high retention, and clear \noutcome ascertainment provide strong  evidence of single -dose vaccine efficacy for individuals \nup to age 23  years . Efficacy against HPV types 16/18 and the seven high -risk types showed a \nlower confidence interval bound  above 94%, consisten t with licensure trials for 3 doses, with no \nevidence of waning protection. Exploratory analyses from the intention -to-treat population found \nhigh protection once prevalent infections at vaccination had cleared.  \n34 \n Ms. Cassandra Pingali (CDC/NCIRD)  shared the data summary for the 2023 National \nImmunization Survey -Teen (NIS -Teen). NIS-Teen  includes a two -phase process: a random digit \ndialed phone survey of parents of teens aged 13 to 17 years and a follow -up mailed survey to \nvaccination providers  (e.g., clinics, pharmacies, health departments)  if permission is granted. \nThe provider data  includes vaccination dates, types, and doses. Coverage estimates are based \non provider -reported data. In 2023, the survey included 16, 568 teens born between January \n2005 and December 2010.  \nCoverage with ≥1 Tdap and ≥1 MenACWY has been high and stable since 2018. However, \ncoverage with ≥1 HPV vaccine and proportion of HPV up to date is lower compared to most \nother routine vaccines.  \nIn 2023, 89 .0% of adolescents aged 13 to 17 years had received a Tdap vaccine, 88.4% had \nreceived a MenACWY vaccine, 76.8% had received an HPV vaccine, and 61.4% were up to \ndate on HPV vaccination.  This marks the second consecutive year HPV vaccination coverage \nhas not increased among adolescents aged 13 to 17 years.  \nIn 2023, about 77% of adolescents received an HPV vaccine. The HPV vaccine is commonly \ngiven with other recommended adolescent vaccines, with 69.5% receiving it with one or more \nadditional vaccines in one visit. Among those who received an HPV vaccine, 47.8% received it \nwith both the Tdap and MenACWY vaccines in one visit. \nThe percentage of adolescents who were HPV up  to date  was lower in mostly suburban and \nmostly rural areas compared to mostly urban areas. There were no differences in MSA status \nbetween the Tdap and MenACWY vaccinations . \nOverall, vaccination coverage was lower among uninsured adolescents compared to those with \nprivate insurance across all vaccines. Adolescents with \"other\" insurance also had lower up-to-\ndate HPV  rates than those with private insurance. Coverage was similar between adolescents \nwith private insurance and those with Medicaid, including for the HPV vaccine.  \nHPV vaccination has historically been higher among Medicaid -insured adolescents compared to \nthose with private insurance, as observed from 2015 to 2021. However, in 2022, coverage with \none or more doses declined by three percentage points among Medicaid -insured adolescents. \nAs a result, in 2022 and 2023, HPV vaccine coverage was similar between Medicaid -insured \nand privately insured adolescents.  \nHistorically, Black and Hispanic adolescents have had higher coverage with ≥1 HPV vaccine \nthan White adolescents . In 2023, only Hispanic adolescents had higher coverage.  In 2023, \ncoverage with ≥1 MenACWY was higher among Asian adolescents compared to White \nadolescents.  \nIn 2023 , coverage with ≥1 dose of the HPV vaccine was 77%  in the United States.  Mississippi \nhad the lowest coverage (60%), and Rhode Island had the highest coverage with ≥1 HPV \nvaccine (93%).  HPV vaccine initiation at ages 9 –10 and 11 –12 has increased from 2018 to \n2023, while initiation at age 13 –17 has decreased from 2018 to 2023.  \nDr. Pingali summarized that in 2023, 76.8% of adolescents had initiated the HPV vaccine, and \n61.4% were up to date. This was the second consecutive year without increased coverage, \nwhich remains lower than for Tdap and MenACWY vaccines. Most adolescents began the HPV \nvaccine series at ages 11 to 12, and 47.8% received the HPV, Tdap, and MenACWY vaccines \nin a single visit. HPV vaccination coverage continues to vary by sociodemographic factors, \nhealth care access, and state.  \n35 \n Ms. Moser acknowledged the value of the NIS -Teen and NIS -Child  data in showing national \nvaccination progress . A question was raised about whether data collection will continue or if any \nrecent changes have impacted the ability to gather this information.  \nDr. Pingali confirmed that, as far as is known, data collection for both the NIS -Teen and NIS -\nChild surveys is continuing.  \nDr. Asturias asked whether there are differences in age at HPV vaccine initiation by geographic \nregion in the U.S.  \nDr. Pingali noted that the sample size is likely too small to analyze HPV vaccine initiation among \nthe youngest age group, ages 9 to 10  years , as less than 5% of the national sample initiated at \nthose ages. However, it may be possible to examine state -level data to see if stable estimates \nand differences can be identified.  It was also shared that the group can look at initiation rates \namong adolescents aged 13 to 15 years to identify patterns or differences.  \nDr. Brooks requested clarification on the “up to date” definition in the slide showing data over \ntime from 2015 onward. Specifically, the question was whether \"up to date\" included individuals \naged 9 to 14 years who only needed two doses, as the slide also referenced those with greater \nthan or equal to three doses.  \nDr. Pingali clarified that in NIS -Teen, HPV up  to date is defined as receiving  three or more \ndoses, or two doses if the first dose was given before age 15  years , with at least 5 months \nminus 4 days between the first and second dose.  \nDr. Schechter asked whether there was any evidence of disruptions or delays in vaccine \nadministration among adolescents aged 13 to 17 years during the pandemic, similar to effects \nseen with other vaccines or age groups. There was also a question about the recent \nequalization of HPV vaccination rates between Medicaid -insured and privately insured \nadolescents, whether this trend reflects catch -up among privately insured adolescents, a decline \namong those with Medicaid, or a combination of both.  \nDr. Pingali explained that vaccination coverage dropped notably among children born in 2008, \nwho would have been 12 years of age  during the pandemic. This group appeared to be the \nmost affected. The 2009 birth cohort, who were 11 years of age in 2020, showed fewer \ndisruptions, and the 2010 cohort , the youngest in the 2023 data, had coverage levels similar to \npre-pandemic levels, except for a drop in HPV up -to-date coverage. Regarding the equalization \nin coverage between Medicaid -insured and privately insure d adolescents, there was a 3 \npercentage point drop in HPV coverage from 2021 to 2022 among Medicaid -insured teens. \nWhile the cause is not entirely clear, there is speculation that changes in access to the  VFC \nprogram or other pandemic -related factors may have contributed.  \nDr. Jane Kim (Harvard University) shared estimates of the expected  impact of single -dose HPV \nvaccination on the health of the U.S. population. T wo independently developed mathematical \nmodels were adapted to the U.S. population to project the long -term health impact of single -\ndose HPV vaccination  (Harvard and HPV -ADVISE) . The models accounted for historical HPV \nvaccination coverage . They were  used to explore key uncertainties related to the efficacy and \nduration of protection from a single dose at the population level.  \nThe Harvard and HPV -ADVISE  models are individual -based HPV transmission models that \naccount for herd immunity and reflect multiple birth cohorts by age and sex. They share similar \nstructures but differ in key areas. Both models  include the seven high -risk HPV types in the 9-\nvalent vaccine, but Harvard groups other types, while HPV - ADVISE  models them separately. \nHarvard models transmission by monthly partnership duration, while HPV - ADVISE  uses \n36 \n transmission per sexual act. HPV - ADVISE  also includes an additional CIN1 health state not \ncaptured in the Harvard model.  \nBoth models overestimate the number of lifetime partners compared to U.S. data, suggesting \nhigher assumed HPV exposure, especially in older age groups. This assumption is important \nwhen evaluating the potential waning of protection from a single -dose HPV vaccine.  \nVaccine assumptions were based on existing clinical trial data, including the KEN SHE trial. The \nbase case assumed 98% efficacy for one dose, indicating noninferiority to two doses. A worst -\ncase scenario used 90% efficacy, reflecting the lower bound of pub lished KEN SHE data. For \nthe duration, the base case assumed lifelong protection, matching that of two doses. The worst -\ncase scenario assumed an average duration of 25 years  (normally distributed with standard \ndeviation of 5 years) , with waning starting at  15 years post-vaccination for some individuals and \nno protection for most by 40 years post -vaccination. Both efficacy and duration were assumed \nto be the same across all vaccine -targeted HPV types.  \nResults showed that with 2 -dose or noninferior 1 -dose 9 -valent HPV vaccination, the model s \nproject near elimination of HPV -16 infections and an approximately  90% reduction in cervical \ncancer by the year 2070. Under the worst -case assumption  of vaccine efficacy (90%), 1 -dose  \nvaccination is projected to produce  similar population -level impacts as  2-dose or noninferior 1 -\ndose.  Even with waning 1 -dose  protection (average of 25 years),  1-dose vaccination is \nprojected to  produce similar population -level impacts as 2 -dose or noninferior  1-dose.  Assuming \nboth lower VE (90%) and  waning 1 -dose protection (average  25 years), 1-dose vaccination is  \nprojected to produce  a slight rise in  HPV incidence (~2045) and cervical  cancer incidence \n(~2060).  All scenarios result in similar  reductions in HPV  16 and cervical  cancer incidence over \ntime.  \nCompared to previously published results, the average vaccination age  in the current  analysis is \nat least five years later. With a 25 -year duration, waning occurs when individuals are less \nsexually active. This means a higher percentage remains directly protected at older ages, \nleading to stronger indirect  effects even as protection from one dose declines . \nDr. Kim concluded that the model s suggest switching to  a 1-dose HPV vaccination in the U.S. \nwould result in similar reductions in HPV and cervical cancer incidence as continuing with two \ndoses  in the U.S.  Even under pessimistic assumptions about vaccine efficacy and duration, the \nmodel s project only limited increases in HPV infections and cervical cancer cases. This is \nbecause the switch would occur when HPV prevalence is already low, and most individuals \nwould remain protected during peak sexual activity, providing both direct and indirect  protection. \nContinued monitoring of 1 -dose protection is important to detect any signs of waning and apply \nmitigation strategies if needed. Under pessimistic assumptions, switching back to a 2-dose \nvaccination could help recover potential losses in cancer prevention ; mitigation strategies would \nnot require revaccinating those who received one dose to be successful . The consistent results \nfrom two independent models add strength to these conclusions.  \nDr. Asturias noted that while immunogenicity and efficacy of the HPV vaccine have consistently \nbeen strong, regardless of the number of doses, the key driver of the model’s population -level \nimpact appears to be the indirect effects, such as herd immunity. He asked for confirmation that \nthe broader impact is less about the individual immune response and more about how many \npeople are protected overall, which ultimately drives the population -level outcomes.  \nDr. Kim confirmed that this is correct, emphasizing that strong indirect or herd effects from HPV \nvaccination are already being observed in the U.S. population. While direct protection is \nimportant, it also contributes to broader population resilience by protecting unvaccinated \nindividuals through indirect  effects.  \n37 \n Dr. Brooks asked whether the modeling accounted for a potential delay in detecting a rebound \nin HPV infections or cervical cancer cases , leading to delay in initiating mitigation efforts . \nDr. Kim responded that any potential rebound in HPV prevalence would likely be identified \nthrough clinical trial data before it becomes evident in epidemiologic trends. Ongoing trials \nmonitor  long-term vaccine efficacy, which helps detect early signs of waning. As shown in \nprevious modeling published in the Journal of the National Cancer Institute , any rebound in HPV \ninfections would occur several years later, with cervical cancer cases appearing even further \ndown the line. If needed, mitigation strategies such as reverting to a 2 -dose schedule could be \nimplemented in time to offset potential losses in health outcomes.  \nDr. Ruth Stefanos (CDC/NCIRD) reviewed the modified EtR framework. Given interpretation \nissues on the HPV vaccination schedule, the policy question  is: \nShould the ACIP recommendations state:  \nHPV vaccination is routinely recommended at age 9 –12 years  \ninstead of:  \nHPV vaccination is routinely recommended at age 11 or 12 years; vaccination can be given \nstarting at age 9 years  \nFor the public health problem, Dr. Stefanos shared that HPV is the most common sexually \ntransmitted infection in the U.S. Persistent infection can lead to precancers and cancers. An \nestimated 37,800 HPV -attributable cancers are diagnosed each year in the U S. \nHPV vaccination coverage has increased since its introduction, but it still lags behind other \nadolescent vaccines. NHANES data show that quadrivalent HPV type prevalence among \nsexually experienced females aged 14 to 24 years in the U.S. dropped from 18.5% in 2003 to \n2006, the pre -vaccine era, to 2.8% in 2015 to 2018. This represents an 85% reduction. Similar \ndeclines were observed among sexually experienced females across different racial  and ethnic  \ngroups.  Declines in cervical precancers have been seen in women aged 20 -24 years since 2008 \nand in women aged 25 -29 years since 2016. Cervical cancer has been declining for several \ndecades in the U.S., due to cervical cancer screening which allows for detection and treatment \nof precancers before progression to ca ncer. Continued declines in cervical cancer in women \naged 21 -24 years are likely a combination of both changes in screening recommendations and \nvaccination impact.    \nThe CDC estimated the annual direct medical costs of HPV -attributable disease in 2020 U.S. \ndollars, published in 2023. The total yearly  cost is $9.01 billion, with $4.05 billion attributed to \ntreatment expenses.  \nThe work group felt that HPV -related disease is of public health importance.  \nFor the benefits, Dr. Stefanos explained that changing the wording for the routine HPV \nvaccination age to 9 –12 years  could offer greater clarity and flexibility. However, potential harms \ninclude the risk of separating the HPV vaccine from the broader adolescent platform, or at least \ncreating the perception of doing so, and possible pushback from providers who prefer to \nvaccinate at age 11  years , as well as from some parents for various reasons.  \nAlthough ACIP currently allows vaccination starting at age 9  years , the wording has confused \nsome partners. Changing the recommendation to state ages 9 –12 years clearly would improve \nclarity. Some providers want to begin vaccination at age 9, but electronic health records often \ndo not prompt vaccination at age 9  due to the current wording. Updating the language could \nhelp address this issue and support those aiming to start vaccination earlier.  \n38 \n In Clinical Decision Support for Immunization ( CDS i) resources, the minimum age for HPV \nvaccination is 9 years, and the earliest recommended age is currently 11  years . Additionally, \nthere is administrative guidance included in the CDSi resources that state the vaccination can \nbe given starting at age 9 years.  \nWhile some systems reflect this in their prompts, most clinical decision support tools use the \nearliest recommended age to trigger alerts. As a result, prompts for HPV vaccination typically \nbegin at age 11. Changing the wording of the routine vaccination recommendation to ages 9 – \n12 years would update the earliest recommended age to 9 in CDSI tools, prompting HPV \nvaccination starting at age 9.  \nThe policy under consideration is to change the recommended age wording to 9 –12 years, not \nto set a new recommendation specifically for ages 9 –10 years . A review was presented to ACIP \nin October. It found that starting HPV vaccination at ages 9 –10 years was associated with \nhigher series completion by age 13 compared to starting at 11 –12 years . However, limitations in \nthe studies prevent conclusions about cause and effect. Few children began vaccination at 9 –10 \nyears , and there may have been differences in families or providers vaccinating at ages 9 –10 \nyears . Additionally, multi -component interventions make it difficult to isolate the impact of \ninitiation  at ages 9 –10 years . \nFor the harms, Dr. Stefanos shared that some have raised concerns that changing the wording \nmay negatively affect the adolescent vaccination platform. While there are no data on what the \npotential harm  might be , it is known that the HPV vaccine is often given alongside other \nvaccines.  Among adolescents who  had received the HPV vaccine, 69.5% received it at the \nsame visit with at least one other vaccine.  An additional  concern is that changing the wording \ncould lead to system prompts at age 9  years , and vacci nation at that age may not be acceptable \nto some providers.  \nA majority of work  group members felt that the anticipated desirable effects were moderate, \nwhile the undesirable effects were considered minimal or small. A majority of work  group \nmembers felt that the desirable effects outweigh the undesirable effects and favor  a change in \nwording.  \nFor the acceptability and values domain s, Dr. Stefanos shared that one study interviewed \nproviders and nurses involved in an intervention including vaccination at age 9, and they \ngenerally had a positive experience. A small qualitative study in a rural setting found mixed \nopinions. Three clinici an surveys were also conducted, with one showing that 61% of providers \nnot currently recommending vaccination at age 9 were willing to do so. The surveys found that \nprovider r ecommendations varied by provider special ty, patient age group, and framing of the \nrecommendation . Only two studies in the systematic review examined parents' perceptions of \nvaccination at ages 9 –10 years . While few parents reported receiving recommendations to \nvaccinate before age 11  years , most were willing  to do so.  \nDr. Stefanos summarized that the AAP recommends starting the HPV vaccination  series \nbetween the  ages of 9 and 12 years , and some stakeholders and advocacy groups support \nstarting at age 9. Changing the wording would clarify that vaccination at age 9 aligns with ACIP \nrecommendations. However, other stakeholders are concerned that this change could weaken \nthe adolescent vaccination platform. In a limited number of studies, vaccination at ages 9–10 \nwas acceptable to providers and parents.  \nWork  group members felt that changing the wording of the routine vaccination age to 9 –12 \nyears  was acceptable to stakeholders, with most responding \"probably yes\" or \"yes.\" For parent \nvalues, limited data were available for review, and a plurality of work  group members responded \n\"don't know\" to the question about whether parents feel that desirable effects of changing the \n39 \n wording are large relative to the undesirable effects . Regarding uncertainty or variability in how \nmuch parents value  changing the wording of the recommendation , a plurality indicated it was \n\"probably not important,\" while a minority felt it was \"probably important.\"  \nThe remaining domains in the EtR framework  and the summary work group interpretation  will be \npresented  at a future ACIP meeting.  \nDr. Loehr commented that he has not found the adolescent platform to be useful, noting that in \nNew York State, sixth graders require Tdap, and seventh graders need MenACWY, while HPV \nis often mixed in. He observed that most parents do not want multiple vac cines given at once. \nHe expressed openness to hearing a defense of the adolescent platform to better understand  \nthe rationale behind recommending it.  \nDr. Asturias shared that strong evidence supports the efficiency of a 1 -dose approach, which \nwould nearly halve program costs and reduce the number of doses needed to provide the same \nlevel of protection. He agreed with Dr. Loehr in discouraging the term \" platform,\" emphasizing \nthat the role of ACIP members is to base recommendations on evidence, prioritizing \neffectiveness, fewer doses, and safety.  \nMs. Moser noted that data show the HPV vaccine is often given with other vaccines, even if not \nin every practice. She expressed concern that the undesirable effects may be underappreciated, \npointing out that provider surveys indicate many parents are not r eady to discuss vaccination at \nage 9. She also emphasized that the data on parental support for earlier vaccination were \nlimited. Additionally, she suggested that some potential benefits, such as improving how the \nvaccine fits into the schedule,  could be a ddressed without this change and  CDSi tools could be \nenhanced to allow more flexibility for institutions that prefer to recommend HPV vaccine \nbeginning at age 9 years . She questioned whether some of the stated benefits were as clear -cut \nas presented.  \nMs. Lyons commented that the adolescent platform will likely be reviewed in connection with \nmeningococcal vaccines, suggesting that changes to the platform may be forthcoming \nregardless. It was noted that this potential review should be considered and may re duce \nconcerns about harm from altering the HPV vaccination schedule.  \nDr. Lauri Markowitz (CDC/NCIRD) shared the work  group’s next steps and considerations. The \ntwo policy questions under review are the wording of the recommendation for routine \nvaccination age and the number of doses in the recommended HPV vaccination series.  \nIn October, the topic was introduced to ACIP along with a review of data on vaccination at ages \n9 to 10. The work  group found no strong evidence that starting at age 9 years improves \ncoverage compared to starting at 11 to 12  years . The plan is to clarify the recommendation by \nchanging the routine vaccination age wording to 9 through 12  years , making it clear that age 9 \nyears is included. Dr. Stefanos presented part of the modified E tR today ; because this is a \nminor wording change rather than a change to the  recommended age , GRADE is not being \nused . The remainer  of the E tR will be presented in June.  \nIn October, the work  group also introduced the topic of the number of doses in the HPV \nvaccination series and reviewed key studies supporting reduction  in the number of doses , along \nwith global updates on one -dose recommendations. Today’s presentations included updated \ndata from major studies, a randomized trial (KEN SHE), U .S. coverage, and modeling. The work  \ngroup will continue focusing on this policy question through June. At the June meeting, data \nfrom the ESCUDDO  trial comparing one versus two doses wi ll be presented, along with any \nadditional data requested by ACIP, a full E tR framework with GRADE, and, if ready, votes on \nboth policy questions.  \n40 \n Dr. Markowitz explained that  ESCUDDO , the randomized trial in Costa Rica sponsored by the \nU.S. National Cancer Institute, is evaluating whether one dose of the bivalent or 9-valent HPV \nvaccine is noninferior to two doses in preventing HPV 16/18 infections in girls aged 12 to 16  \nyears . It will also compare vaccinated participants with unvaccinated women using survey data. \nResults are expected before the June meeting and will be presented to ACIP.  \nOutstanding questions remain regarding the number of doses, especially in three key areas. \nFirst, on the duration of efficacy and immunogenicity of one dose, current data show protection \nthrough 15 to 16 years with no evidence of waning, and more data are expected. Second, there \nare no data on the protection at sites other  than the cervix. Third, for males, 13 of the 16 studies \nreviewed included only females, and one -dose efficacy in males is not yet available. Some \nstudies have found that antibody levels a fter one HPV vaccine dose are lower in adolescent \nmales than in females; however, the clinical relevance is unclear.  \nIn March 2024, Merck announce d plans for  clinical trials for 1-dose HPV vaccination.  Two \ninternational, randomized , double -blind, efficacy clinical trials are planned , one in males 1 6-26 \nyears of age, and one in females 16 -26 years of age.   The planned trials include elements \nregulators have deemed necessary , including endpoints other than persistent cervical infection  \nand a comparison of 1 -dose and 3 -dose efficacy.  Merck has been in discussions with FDA and \nEMA regarding trial design;  regulatory feedback  is an ticipated in Q2 2025.  \nIt would be considered off -label if ACIP recommends one dose at any age or a two -dose \nschedule for individuals aged 15 or older . Off-label use refers to anything not included in, or \ndiffering from, the FDA package insert. Manufacturers can only promote and provide education \non FDA -licensed indications . It is important to note that ACIP has made many off -label \nrecommendations in the past, and at least 46 licensed vaccines in the U.S. have  some  off-label \nrecommendations, most of which apply to specific situat ions or subgroups.  \nThe HPV Vaccines Work  Group is considering potential modifications to current \nrecommendations as data are reviewed. One option is expanding the 2 -dose recommendation \nfrom ages 9 through 14 years to ages 9 through 26 years or through an older  age. Another \noption under discussion is recommending 1 dose for certain age groups, such as 9 through 14  \nyears , 9 through 20  years , or through an older age.  \nDr. Markowitz concluded that all work  group members support modifying the HPV vaccination \nschedule . However,  there are differing views on expanding the 2 -dose schedule or \nrecommending  1 dose for certain age groups. The work  group continues  to review data and \ndiscuss the appropriate upper age range for these potential changes.   She closed with \nquestions for the committee on any questions or comments regarding the policy questions to be \naddressed, and what additional information ACIP would like to see be fore potentially voting at \nthe next meeting.  \nDr. Middleman commen ted on  the importance of vaccination platforms for adolescents, drawing \na parallel to the well -established platforms for infants and young children, which are deeply \nintegrated into anticipatory guidance and comprehensive care. It was noted that adolescent \nplatforms serve a similar purpose and contribute to consistent healthcare delivery. Data from the \n2007 NCQA State of Health Care Quality report showed that adolescent immunization rates \namong commercial payers rose from 10.5% in 1998 to 57.7% by 2006, following  the introduction \nof new adolescent vaccines and the VFC program. This suggests that the formation of the \nadolescent platform significantly improved vaccination rates. Additionally, upcoming data from \nDr. Zimet  is expected to show that many parents value the structure and expectations provided \nby vaccination platforms. Using existing data  was encouraged  when evaluating the role of \nplatforms in adolescent immunization.  \n41 \n Ms. Arthur noted that the company is pursuing an FDA indication for a 1 -dose HPV vaccine, \nsimilar to the previous change from a 3 -dose to a 2 -dose schedule. She emphasized the \nimportance of alignment between agencies like the FDA and the CDC/ACIP process. She also \nhighlighted that the company would address  key data gaps discussed during the meeting, \nincluding the efficacy of 1 dose in males. Ms. Arthur stressed the importance of maintaining \nconsistency and high evidentiary standards and encouraged considera tion of all available \nevidence in the decision -making process.  \nMs. Lyons encouraged the work  group to review the small number of states requiring  the HPV \nvaccine to ensure that moving to a 1 -dose schedule or making other changes does not impact \nexisting school entry requirements.  \nDr. Loehr responded that he is comfortable with the idea that earlier dosing provides better \nprotection, referencing a slide from the first presentation. He acknowledged that a 1 -dose \nschedule has a lower seropositivity rate but noted uncertainty about the  clinical relevance of that \ndifference. He referenced Dr. Kim’s point that indirect  effects may be more impactful than \nseropositivity. Dr. Loehr stated he would be more comfortable supporting fewer doses if there \nwere evidence that lower seropositivity is not clinically significant . He expressed interest in \nseeing more data on that issue.  \nDr. Markowitz clarified that Dr. Kim was referring to vaccine efficacy, noting that strong herd \nprotection could offset a small decline in individual efficacy. She explained that while antibody \ntiters are lower with one dose compared to two or three, no established minimum antibody level \nis required for protection. Therefore, the clinical relevance of lower titers is uncertain. Dr. \nMarkowitz emphasized that efficacy data from studies such as KEN SHE, the Costa Rica \nvaccine trial, and the IARC India study sh ow high protection with one, two, or three doses .  \nDr. O'Leary noted that the American Academy of Pediatrics recommends HPV vaccination at \nages 9–12 years . He expressed that he has not seen compelling evidence supporting the \nconcept of the adolescent platform. He acknowledged that observational data suggest  that \nallowing vaccination at ages 9 –10 may be beneficial. Ultimately, he emphasized that this may \nbe the only case where the wording of an ACIP recommendation itself serves as a barrier to \nvaccination, by not clearly emphasizing the flexibility to begin at age 9.  \nDr. Middleman expressed that the primary concern of the Society for Adolescent Health and \nMedicine is to follow the evidence. While a change in recommendation would make sense if the \nevidence strongly supported it, there is concern that current evidence ma y not be sufficient and \nthat potential harms are also hard to conclusively identify . The goal is to increase HPV \nvaccination without unintentionally weakening the broader adolescent vaccination platform. It \nwas emphasized that any changes should be grounde d in evidence and that the current wording \ndoes not appear to discourage vaccination.  \nMs. Moser emphasized that this is a communication issue, not a change in recommendation. \nSince HPV vaccination is already allowed at age 9  years , she cautioned that changing the \nwording could raise concerns among parents and providers, especially given sensitivities \naround the vaccine. The impact of the wording change on overall uptake should be carefully \nconsidered.  \n \nCYTOMEGALOVIRUS (CMV ) VACCINES \n \nDr. Denise Jamieson (ACIP, Work  Group Chair) introduced the launch of the Cytomegalovirus \n(CMV) Vaccines Work Group. The work  group will review CMV and congenital CMV (cCMV) \n42 \n epidemiology  and disease burden, CMV vaccine safety and immunogenicity data, and initial \nwork group considerations for CMV vaccine policy.  \n \nDr. Tatiana Lanzieri (CDC/NCIRD ) reviewed the epidemiology and disease burden of CMV and \ncCMV. cCMV is the most common infectious cause of congenital birth defects  in the U .S., \naffecting over 16,000 newborns annually  and is the leading non -genetic cause of childhood \nhearing loss . It causes  an estimated 80 neonatal deaths and nearly 3,000 cases of cCMV  \ndisease each year, with long -term outcomes including hearing loss, cognitive, or motor \nimpairments.  \n \nCongenital CMV may present at birth with signs  like rash, enlarged liver or spleen, or a small \nhead. Diagnosis is typically by PCR or culture of urine, blood, or cerebrospinal fluid within 21 \ndays of life. Most newborns with cCMV infection have no clinical signs at birth  and go \nundiagnosed. To improve detection, some U .S. states have implemented targeted or universal \nscreening  for cCMV . \n \nIn the U .S., two states have implemented universal newborn screening for cCMV, while 11 \nconduct targeted hearing screening. Three of those states also perform symptom -based \nscreening. Additionally, 13 states are conducting cCMV surveillance.  Data from all states are \nunavailable;  cCMV prevalence likely varies by state due to differences in maternal age, \ndemographics, and population -specific CMV rates.  Data from CDC’s National Health and \nNutrition Examination Survey (NHANES) has shown that CMV IgG seroprevale nce increases \nwith age. From the 1988 -1994 NHANES cycle to the 1999 -2004 cycle , age-specific rates among \nthose aged 6 –49 years remained stable. However, from 2011 -2012  to 2017 -2020, \nseroprevalence among  children aged 1 –5 years rose from 21% to 29%. Updated testing for \nages 6 –59 years from the 2017 –2020 NHANES cycle is ongoing.  \n \nCMV seroprevalence is higher among non -Hispanic Black and Hispanic women compared to \nnon-Hispanic White women. Among women aged 20 –29, rates are 36% for non -Hispanic White \nand 77 –81% for non -Hispanic Black and Hispanic women.  \n \nSeronegative women are at risk for primary CMV infection during pregnancy, while seropositive \nwomen may experience reinfection. The risk of vertical transmission is highest with primary \ninfection and increases by trimester, but severe outcomes like hearing  loss are more likely with \nfirst-trimester infections. Non -primary infections have lower vertical transmission rates but can \nstill cause cCMV disease if transmission occurs early  in pregnancy . These findings suggest that \na CMV vaccine should be given befor e pregnancy to protect against vertical transmission \nfollowing primary infection . \n \nThe incidence of CMV primary infection and reinfection varies across populations. Proportions \nof cCMV infections due to non -primary maternal infection (NPI) vary with maternal \nseroprevalence . Still, the  risk of cCMV infection is higher when the mother is CMV seronegative \nbefore pregnancy. About 12,000 (75%) cCMV infections in the U.S. every year may be \nattributable to primary maternal infections.  \n \nYoung children play a key role in CMV transmission, shedding high virus levels  in saliva and \nurine for months after infection. Shedding peaks at 1 to 2 years of age, which is also when many \nfirst-time mothers in the U .S. have a second pregnancy.  \n \nModeling suggests that a vaccine given to infants, even if the duration of protection was short , \ncould impact transmission to pregnant mothers and decrease cCMV infections. Models predict a \n43 \n varying  impact depending on the population to be vaccinated, vaccine efficacy, duration of \nprotection , and coverage . \n \nDr. Lanzieri summarized that CMV and cCMV epidemiology are complex and have many \nunknowns. In the U .S., most cCMV cases are linked to primary maternal infection, while \nglobally, non -primary infections are more common. A CMV vaccine could reduce disease \nburden by providing long -lasting protection before and during pregnancy or indirectly protecting \npregnant  women if given to toddlers.  \n \nDr. Robert Paris (Moderna) presented an overview of the investigational CMV vaccine, mRNA -\n1647. Globally, cCMV affects 1 in 70 to 1 in 208 births. It occurs in about 1 in 200 births in the \nUS, with annual healthcare costs of $6 to $7 billion. Approximate ly 1 in 5 infants with cCMV \n(symptomatic or asymptomatic at birth) develop long -term disability. Limited options for \nprevention, screening, and treatment make cCMV a major unmet medical need and a high \npriority for vaccine development, as recognized by the WH O and the U.S. National Academy  of \nMedicine.  \nThe clinical program aims to prevent CMV infection in seronegative women by vaccinating \nwomen of childbearing age before pregnancy, when the risk of transmission and complications \nis highest. Due to the low incidence of cCMV and long -term outcomes, a large , lengthy Phase 3 \ntrial would be impractical. Instead, the initial indication will target CMV prevention in females \naged 16 to 40  years of age , regardless of CMV serostatus.  \nModerna’s investigational CMV vaccine (mRNA -1647) contains six mRNAs designed to elicit \nboth humoral and cellular immunity. Antigens were selected to prevent CMV infection and fetal \ntransmission.  Five mRNAs encode the pent amer subunits, required for CMV entry into most cell \ntypes ; the other mRNA encodes glycoprotein B  which mediates fusion of virus and host \nmembranes during cell entry , which is necessary for viral infectivity.   Prior gB -based vaccines \nshowed 43 –50% efficacy ; adding  the pentamer glycoprotein  in mRNA -1647 is expected to \nimprove efficacy.  \nThe Phase 1 trial was a randomized, placebo -controlled study of mRNA -1647 in healthy adults \naged 18 to 4 9 years of age , assessing doses from 30 to 300 micrograms. Among 154 \nparticipants, over half were CMV negative, and the vaccine was well tolerated with no safety \nconcerns. CMV -negative and -positive participants showed neutralizing antibodies, binding \nantibodies, and cell -mediated responses. These results supported continued development and \ninformed dose selection within a narrower range.  \nIn the Phase 2 study, 315 adults aged 18 to 40 were randomized 3 :1 to receive mRNA -1647 or \nplacebo on a 0 -, 2-, and 6 -month schedule. About 70% were CMV negative and followed for \napproximately 12 months post -vaccination. Dose levels of 50, 100, and 150 micrograms were \nevaluated in Part 1, while Part 2 focused on additional safety and immunogenicity data for the \n100 microgram dose  which was the dose selected for the Phase 3 efficacy trial . The primary  \nobjectives were safety and neutralizing antibody response s. \nSolicited local reactions were self -reported by participants within 7 days for each injection. Pain \nwas the most frequent local reaction , reported by about 80% of participants ; local reactions \nwere mostly grade 1 or 2 and generally 1 -3 days in duration.   For systemic rea ctogenicity, \nheadache, fatigue, myalgia, and chills were most common.  There was some increase in \nsystemic reactions with second  and third doses .  Systemic reactions were generally grade 1 or \n2 and of 1-2 days duration.   Related medically -attended adverse events  (primarily local injection \nsite reactions) occurred more frequently in vaccine recipients than placebo recipients.  No \nsignificant safety concerns were identified during the study.  \n44 \n Neutralizing antibody res ponse  to mRNA -1647 was based on bo th epithelial cell  and fibroblast \ncell assays  to assess responses to both the pentamer and the gB  antigen.  Among CMV \nseronegative participants , as assessed by epithelial cell infection, GMTs increased after each \ndose and remained above the GMT seen in natural infection through 18 months ; as assessed \nby fibroblast infection, GMTs reached the natural infection GMT at months 3 and 7, and then \ndeclined at months 12 and 18.   Among seropositive participants,  after the first dose  antibodies \nagainst epithelial cell infection increased approximately 17 -fold over baseline , and antibodies \nagainst fibroblast infection increased about 2.4 -fold over baseline ; the second and third doses \ndid not appear to substantially increase antibody titers .  GMT s for both assays remained above \nthe natural infection GMT through month 18.  \nDemonstrating durable immune responses is key for vaccine implementation. Long -term follow -\nup is underway in Phase 2 and 3 trials to assess immunogenicity and efficacy. Phase 2 \nparticipants were offered enrollment in an extension study with three additiona l years of follow -\nup. An interim analysis was recently conducted on data up to 36 months post -vaccination.   \nDurable immune response was observed through three years after the first vaccination  among \nseronegative participants , with GMTs remaining stable fro m 18 to 36 months  for both assays ; \nDr. Paris stated that results were similar for the seropositive cohort.  \nDr. Paris summarized that mRNA -1647 was generally well tolerated with no safety concerns \nidentified . The 3-dose 100 microgram regimen was highly immunogenic . Neutralizing antibody \nGMTs against epithelial infection remained above natural infection GMT through 12 months \nafter the last vaccination in SMV -seronegative participants ; a boost ing effect was observed in \nCMV -seronegative participants. The vaccine induced durable epithelial and fibroblast \nneutralizing antibody responses lasting up to three years.  \nThe Phase 3 pivotal efficacy trial is a randomized, observer -blind, placebo -controlled study \nenrolling females aged 16 to 40  years of age . CMV -positive participants help assess safety and \nimmunogenicity, while CMV -negative participants aged 20 and older had to have regular contact \nwith a child under five  years of age . Pregnancy was an exclusion criterion. Participants were \nrandomized 1:1 to receive 100 micrograms of mRNA -1647 or placebo on a 0 -, 2-, and 6 -month \nschedule, with two years of follow -up after th e third dose to assess efficacy.  \nThe trial's primary objective  is to evaluate vaccine efficacy against primary CMV infection in the \nseronegative cohort, measured by seroconversion to CMV IgG positivity. Participants undergo \nserology testing every three months starting 28 days after the last dose. Immunogenicity is a \nkey secondary objective, using endpoints and assays consistent with prior studies. CMV \nshedding is also being assessed through PCR detection of CMV DNA in urine samples after \nseroconversion and in CMV -positive participants thro ughout the study.   \nThe study is being conducted in 290 sites in 13 countries.  Enrollment was completed in \nOctober 2023, with 7,484 participants enrolled ; 80% were CMV -seronegative  and 20% were \nCMV -seropositive.  The mRNA -1647 Phase 3 efficacy trial includes two planned analyses. An \nindependent Data Safety Monitoring Board (DSMB) conducted an interim efficacy analysis in \nDecember 2024. The DSMB found no safety concerns and recommended that the study \ncontinue as planned in a blinded manner. The final efficacy analysis is antic ipated in late 2025.  \nDr. Paris concluded that mRNA -1647 has been generally well tolerated in adults aged 18 to 40, \nregardless of CMV serostatus, in Phase 1 and 2 trials. The DSMB identified no safety concerns  \nduring its review of unblinded Phase 3 data. In seronegative participants, the vaccine elicited \nantibody responses that exceeded those seen in natural infection, with immune persistence \nobserved through three years. In seropositive participants, vaccinati on boosted immune \nresponses above baseline after the first dose. The Phase 3 efficacy trial is ongoing in \n45 \n seronegative and seropositive females aged 16 to 40  years , with the final efficacy analysis \nexpected by the end of th is year.  \nDr. Shaw asked about  previous studies using subunit vaccines, specifically those containing the \npentamer complex and glycoprotein B ectodomain in nonhuman primate model, that found that \nhigh neutralizing antibody levels did not prevent substantial horizontal transmission. He inquired \nif the expectation is that the mRNA platform or use in humans will produce better outcomes. He \nalso asked which specific antibody responses are believed to b e necessary to prevent vertical \ntransmission to the infant.  \nDr. Paris responded that there is still limited understanding of the specific or dominant antibody \nresponse required to prevent vertical transmission. Regarding the nonhuman primate study, he \nacknowledged familiarity with it, stating it was likely conducte d by Pfizer and involved a \nrecombinant pentamer vaccine with glycoprotein B. He noted limitations in the study design, \nparticularly related to the transmission model.  \nDr. Wu (Moderna) noted that the study used rhesus CMV (RhCMV), which, while part of the \nsame beta herpesvirus family, may have a different pathogenesis than human CMV. A key \nchallenge in the CMV research community is the inability to use human CMV to infect animal \nmodels. As a result, studies must rely on species -specific CMV, which limits how well animal \ndata can be translated to humans.  \nDr. Zucker asked whether there is a known correlate of protection for CMV, noting that , based \non the discussion, there may not be one currently identified. She also asked about expectations \nfor individuals who are already seropositive, questioning whether vaccination is expected to \nprevent reinfection or if those individuals would remain at risk upon re -exposure.  \nDr. Paris responded that there is no known correlate of protection for CMV. Seropositive \nindividuals were deliberately included in the clinical development program because they still \nface a significant risk of vertical transmission due to reinfection or re activation, with most cases \nnow believed to result from reinfection. Demonstrating impact on reinfection is challenging, as \ncurrent research tools are limited and unsuited  for Phase 3 trials. Post -licensure, the plan will \nexpand the clinical program to ass ess real -world effectiveness, including the impact on \ncongenital infection in both CMV -negative and CMV -positive populations. While the biological \nsignificance is not fully understood, a reduction in viral shedding could indicate the vaccine’s \npotential to  limit viral replication and reduce transmission in seropositive individuals during \npregnancy.  \nDr. Zucker followed up by noting that approximately 1,800 participants in the study were \nseropositive and asked about the expected incidence of CMV shedding over the course of the \nstudy.  \nDr. Paris responded that the point prevalence of CMV shedding in seropositive individuals likely \nranges from 5% to 20%, depending on how recently they were infected. He noted that the study \nmonitors this continuously and collects  specimens frequently enough to expect detection of a \nsignificant frequency of viral shedding in this population.  \nDr. Asturias inquired whether the antibodies have been tested for their ability to neutralize \nvarious strains of CMV and how many strains they can neutralize. He also acknowledged that \ncellular immunity data from the Phase 2 trial won’t be presented , but wondered if there were any \ninsights on cellular immunity development from the Phase 1 study.  \nDr. Paris referenced a paper published in the Journal of Virology  that assessed wild -type clinical \nstrains of CMV using Phase 1 trial data. The study found no significant impact on neutralization \nacross different viral strains. Regarding T -cell immunity, Dr. Paris confirmed that Phase 1 data \n46 \n showed the induction of T-cell immunity  using an ELISPOT  assay. The team is now evaluating \nthese data with a more recent ex vivo intracellular cytokine assay  which  they hope to present \ndata at an upcoming meeting, showing evidence of T -cell responses immediately after \nvaccination and up to 12 months later. He also noted that, similar to other mRNA -based \nvaccines, they expect robust T -cell immunity.  \nDr. Tatiana Lanzieri (CDC/NCIRD)  followed up with the work  group’s initial considerations for \nCMV vaccine policy. The burden of congenital CMV is substantial, yet awareness is low. \nVaccine acceptability among the public and providers, as well as the feasibility of \nimplementation, needs assessment. Primary maternal infections, which vary by population \nsusceptibility, cause most cCMV infections in the U.S. and lead to more severe disease in the \nfirst trimester. Vaccination before pregnancy and long -lasting protection throughout childbearing \nyears are necessary. CMV seroprevalence increases with age, but certain populations have \nhigh prevalence by adolescence . \nThe Moderna CMV mRNA vaccine candidate encodes the CMV gB and pentamer complex with \na three -dose schedule over six months. The ongoing Phase 3 trial includes 7,500 non -pregnant \nfemales aged 16 to 40  years of age , with about 5,000 CMV seronegative at enrollment. The \nseronegative group will be evaluated for the primary endpoint of vaccine efficacy, while safety \nand reactogenicity will be assessed in all participants. Participants will be followed for 24 \nmonths afte r the third dose, with a subset followed for 48 months.  \nThe work  group reviewed data from Moderna's mRNA -1647 Phase 1 and Phase 2 trials, with \ninitial findings indicating no safety concerns and promising immunogenicity. There is a need to \nbetter understand  differences in neutralizing antibody levels against epithelial cell and fibroblast \nentry  and the cell -mediated immune response, including antibody -dependent cellular cytotoxicity \nand phagocytosis. Regarding long -term protection, the Phase 2 extension data show antibody \npersistence for at least three years afte r the first dose . Still, it  remains important to determine if \nprotection lasts throughout childbearing years.  \nModerna’s planned vaccine indication is for non -pregnant females aged 16 –40 years , with a 3 -\ndose series over 6 months. Efficacy will be assessed for primary infection in initially CMV -\nseronegative subjects. Data on immunity duration will be limited ; protection is needed before \npregnancy and throughout childbearing years. Efficacy against vertical transmission and cCMV \ninfection or disease is yet to be determined. A better understanding of the correlates of \nprotection against vertical transmission is needed.  The benefit for CMV -seropositive individuals \nremains unclear, and serological testing prior to vaccination presents implementation \nchallenges. Vaccine recommendations may evolve as future clinical trial data becomes \navailable for other groups, such as ado lescents and transplant patients.  Over the next several \nmonths, the CMV work  group will continue to review data as it becomes available and address \nadditional domains within the E tR framework.  \nDr. Lanzieri concluded by emphasizing that an effective CMV vaccine could reduce disease \nburden, with over 16,000 children born with cCMV infection in the U.S. each year, nearly 3,000 \nwith cCMV disease. The mRNA -1647 CMV vaccine has shown safety and immunogenic in \nPhase 1 and 2 trials, with efficacy data from the ongoing Phase 3 trial expected next year. The \nvaccine should be given before pregnancy to prevent infection and reduce vertical transmission, \nespecially in the first trimester. Protection against non -primary infections is also i mportant. \nChallenges may include low awareness of cCMV and the need for serological screening before \nvaccination. The CMV ACIP work  group will regularly  review data and develop vaccine policy \noptions.  \nDr. Shaw inquired about potential plans to test the vaccine in transplantation settings, where \nreactivated CMV disease remains a significant issue. He noted that CMV reactivation in aging \n47 \n immune systems can skew the CD8 cell repertoire and asked if there are any ongoing studies or \nplans related to this context.  \nDr. Paris confirmed that testing the vaccine in transplant settings is an active part of their \nprogram. Moderna is currently  conducting a study on  hematopoietic stem cell transplant \nrecipients, with ongoing enrollment. He acknowledged the significant unmet medical need in \nboth stem cell and solid organ transplant populations due to CMV. Regarding the impact of \nCMV on aging and immune response, Dr. P aris noted ongoing discussions and welcomed input \nfrom the work  group on how to address this issue as it relat es to an aging population.  \n \nU.S. MEASLES UPDATE \n \nDr. Talbot began her introduction of the session with a statement that she finds it devastating  \nthat this update was needed; the measles vaccine is very effective  with a long duration of \nprotection , and children in the U.S. should not be dying of measles.  \n \nCAPT  David Sugerman (CDC/NCIRD) shared an update on measles. Before the measles \nvaccine, there were 3 to 4 million cases annually in the US, with 500,000 reported. Cases \ndropped significantly after the vaccine was introduced in 1963. In 1989, the ACIP recommended \na second dose at school entry due to school outbreaks. By 2000, the U.S. achieved measles \nelimination, defined as the absence of continuous spread of the disease for 12 months.  \n \nSince measles elimination, there have been 11 large outbreaks in the U.S. with more than 50 \ncases. Seven outbreaks occurred in the last 5 years, and nine were among close -knit \ncommunities with low vaccine coverage. Coverage in these communities was far below the 95% \nthreshold needed for herd immunity. The most recent outbreak, c oncentrated in Gaines County, \nTexas, involved a 2 -dose MMR coverage rate of 82% in public schools, with true coverage likely \nlower due to homeschooling or private schools without rep orted coverage. The outbreak spread \nto 21 additional counties in Texas and three counties in eastern New Mexico.  \n \nFrom elimination until the COVID -19 pandemic, MMR coverage remained above the 95% \nthreshold needed for herd immunity. However, coverage has decreased since the pandemic. \nDuring the 2023 –2024 school year, approximately 280,000 (7%) kindergarteners lacked \ndocumentation of two MMR doses, potentially putting them at risk for measles. MMR coverage \nalso varies across states, with several reporting coverage below 90%. Coverage is also quite \nheterogeneous at the county level , potentially hiding true outbreak risk.  \n \nFollowing the COVID -19 pandemic, measles has resurged due to increased transmission \nabroad, a surge in international travel, and declines in vaccination, especially in close -knit \ncommunities with already low coverage.  Cases rose from 59 in 2023 to 285 in 2024, and by \nApril 10, 2025, had more than doubled to 712.  \n \nFrom 2023 to 2025, the number of outbreaks fluctuated between 4 and 16  per year , while the \nproportion of total cases linked to outbreaks increased from half to 93% this year, with five \noutbreaks ongoing. Efforts will focus on tracking the duration of these outbreaks and working \nclosely with state and local partners to ensure the 12 -month threshold is not exceeded, \npreserving elimination status, especially wit h ongoing spring and summer travel and congregate \nevents.  \n \n48 \n As of April 10, 2025, 712 cases have been reported by 25 states  in 2025 ; most states are \nreporting no or limited spread from importations . Over 90% of current national cases are linked \nto the southwest outbreak, driven by transmission in close -knit, under -vaccinated communities \nwith low vaccine coverage. There  are currently  large outbreaks in the same close -knit \ncommunity as the southwest outbreak in Ontario, Canada, and Chihuahua, Mexico.   \n \nThere are two circulating measles genotypes in the US: B3 and D8, with D8 being the \npredominant genotype. Four distinct sequence identifiers (DSIDs) have been identified for B3 \nand six for D8 this year. In this outbreak, most sequences are D8 DSID 9171, fo und in Texas, \nOklahoma, New Mexico, Kansas, and  Chihuahua, Mexico, and Ontario, Canada, within the \nsame under -vaccinated community. Four other D8 DSIDs, differing by one to two nucleotides, \nare also linked to the Texas outbreak. Most B3 sequences are from Vietnam, which is \nexperiencing a large outbreak.  \n \nCDC ’s 2025 measles outbreak response efforts include  a variety of initiatives across different \nareas. From March 4 through April 1 , 15 CDC deployers provided on -site technical assistance in \nTexas, with additional teams deploying this week. Remote technical assistance was provided to \nstate health departments. Biweekly national measles calls with public health partners  and \ntrilateral calls with Canada and Mexico  were held to share updates and lessons learned. \nAdditional MMR vaccine doses were made available to health departments. Provider outreach \nincluded releasing a Health Alert Network (HAN) advisory on the expanding measles outbreak \nin Texas and New Mexico and  guidance for the upcoming travel season. Clinician Outreach and \nCommunication Activity (COCA) and Epi -X alerts were issued, and a provider letter was shared \nsummarizing routine and outbreak -related MMR vaccination recommendations. Laboratory \nsupport effor ts included coordination with the Association of Public Health Laboratories Vaccine -\nPreventable Disease Reference Centers for genotyping and sequencin g; expanded testing for \nwastewater surveillance with the National Wastewater Surveillance System and the Center of \nExcellence in Texas ; and ongoing modeling to assess risk.  \n \nDr. Asturias noted that in the Texas outbreak, with two deaths of school -age children and 41 \nreported cases in Lubbock , there’s a case fatality rate of about 4.8%, much higher than the \ntypical measles case fatality rate of 1 –2 per thousand in outbreak situations. He questioned \nwhether this higher mortality might reflect the underreporting of measles cases in the \njurisdiction.  \n \nCAPT  Sugerman confirmed that there are likely many underreported measles cases. In \ndiscussions with families in Texas, some have mentioned prior cases that recovered without \ntesting, while others had cases but never sought treatment. He highlighted under -testin g, under -\ndiagnosis, and under -reporting as contributing factors resulting in a smaller denominator. This is \nparticularly common in close -knit communities with lower healthcare -seeking behavior.  \n \nDr. Zucker asked about resource mobilization during the Texas outbreak, drawing on \nexperience managing the largest measles outbreak in New York City since 1992. The response \nrequired significant resources, with costs around $8.4 million and 7% of the healt h department \ninvolved. Dr. Zucker inquired about the scale of the response in Texas and other areas with \nongoing outbreaks, specifically regarding resource mobilization to end transmission.  \n \nCAPT  Sugerman shared that Texas has requested significant resources. With COVID -19 \nfunding diminishing, Texas is reallocating staff and resources from other domains and regions to \nsupport the measles response. Additional financial and personnel support is neede d, estimated \nat $30,000 to $50,000 per measles case for public health response. While efforts are being \n49 \n made to support Texas and other jurisdictions, securing sufficient resources and personnel \nremains challenging . \n \nDr. Zucker emphasized that it's not just about money, but also the need for adequate staff. It \nwas noted that contact investigations, follow -up communications, and other tasks require \nsignificant personnel, especially for an outbreak of this scale.  \n \nMs. Moser asked when the U .S. could lose its measles elimination status, noting that elimination \nis defined by the absence of continued spread for 12 months.  \n \nCAPT  Sugerman confirmed that the U .S. would lose its measles elimination status after 12 \nmonths of ongoing circulation of the same sequence. With four months in, this would occur \naround January 20th of the following year.  \n \nDr. Kevin Ault (ACOG) inquired about the number of stillbirths, miscarriages, and pre -term \ndeliveries during the current outbreak in Texas, noting the considerable morbidity among \npregnant women in the 2019 New York City outbreak.  \n \nCAPT  Sugerman confirmed that there have been no reports of stillbirths or miscarriages but \nnoted that measles cases in pregnant women, including one case of congenital measles, have \nbeen tracked. He emphasized that pregnant women with measles face significant r isks, \nincluding preterm labor, complicated deliveries, and negative infant outcomes. Additionally, \nthere have been exposures  in hospitals, where pregnant women may not initially show \nsymptoms or a rash, leading to exposure s of others.  \n \nAs a family physician, Dr. Loehr mentioned seeing adults born between 1963 and 1968 who are \nunsure whether they received the killed virus vaccine and need a booster or titer. He noted that \nresearch indicates only a minority from those years received the killed virus vaccine. He asked \nfor suggestions for primary care doctors when facing this question from patients.  \n \nCAPT Sugerman confirmed that less than 5% of vaccines administered between 1963 and 1967 \nwere the inactivated version, which had lower efficacy. He emphasized that most people are \nlikely protected . He stresses the importance of  primary care doctors having  direct \ncommunication with patients. Some may request a titer, while others may prefer an additional \nvaccine. Overall, the risk at the population level is very low due to the small number of \nindividuals who received the inactivated vaccine.  \n \nDr. Talbot highlighted the importance of the work done by CDC colleagues and of available \nvaccines, thanking everyone involved . \n \nDr. Wharton announced that a new webcast link for the following day’s meeting would be posted \nlater in the evening and reminded attendees that it would not be the same link used that day. \nShe thanked all ACIP members for their flexibility in attending the rescheduled meeting, as well \nas the ex officio members, liaisons, and work  group leads for their excellent work. She also \nexpressed appreciation to the ACIP Secretariat for their preparation, CDC’s Office of \nCommunications and NCIRD’s communications team f or their excellent support, and the \nengineers at the CDC’s Global Communications Center for helping the meeting run smoothly. \nShe noted that while many challenges had been anticipated, most were avoided thanks to the \ncollective efforts of everyone involved.  \n \n50 \n With no additional business posed for the day, the ACIP meeting stood in recess until 8:00 AM \non April 16, 2025.  \n \nWEDNESDAY : APRIL 16, 2025 \n \nWELCOME AND INTRODUCTIONS \n \nCall to Order/Roll Call  \n \nDr. Keipp Talbot (ACIP Chair) called to order and presided over the April 16, 2025, Advisory \nCommittee on Immunization Practices (ACIP) meeting. She then conducted a roll call, which \nestablished that a quorum was present. A list of members,  ex officio members , and liaison \nrepresentatives is included in the appendices at the end of this summary document. No COIs \nwere identified for the second day of this meeting. Dr. Chen noted that there was no conflict of \ninterest but stated a decision to abstain from voti ng on chikungunya vaccine items due to prior \ninvolvement in data and safety monitoring board activities. Dr. Kuchel stated there were no \ncurrent conflicts of interest but would abstain from voting on the RSV recommendations due to \nhaving served as a consul tant for approximately six months about a decade ago.  \n \nMENINGOCOCCAL VACCINES \n \nDr. Jamie Loehr (ACIP, Work Group  Chair) introduced the meningococcal vaccines session.  \nThe Meningococcal Vaccines  Work Group has been developing recommendation options for \nGSK’s pentavalent MenABCWY  vaccine, which was licensed on February 14, 2025.  A vot e on \nthis product and a VFC vote is scheduled for this meeting.  The work group is also discussing \nSanofi’s MenACWY (Men Quadfi®) for use in infants.  An extension of licensure  of this product  to \nage 6 weeks is anticipated in May 2025,  to be followed by an ACIP vote in June 2025.   \nAdditionally, t he work group continues to discuss possible changes to the meningococcal \nvaccine schedule for adolescents.  \n \nIn October 2024, the work  group presented an E tR for the GSK pentavalent vaccine and made \na recommendation to the ACIP. At that meeting, the work  group also recommended changing \nthe BEXSERO  schedule from 0 , 1 month to 0 , 6 months based on evidence that longer spacing \nimproved immunogenicity. As a result, some calculations and evaluations had to be redone. The \nGSK pentavalent vaccine, when compared to BEXSERO  with updated data, showed \ncomparatively lower immunogenicity. Some analyses revealed that MenB alone  performed \nbetter  than the  pentavalent vaccine , with non -overlapping confidence intervals. However, there \nis no established clinical correlate of protection, and the clinical significance of these findings \nremains uncertain. The work  group reviewed the changes and updated the E tR accordingly, but \nthe overall recommendation to ACIP did not change.  \n \nDr. Sarah Schillie (CDC/NCIRD) reviewed the updated EtR and work  group considerations for \nthe GSK pentavalent MenABCWY vaccine .  Currently , ACIP recommends  one MenACWY dose \nat age 11 –12 years and a booster dose at age 16 years. Two MenB doses are recommended at \nage 16 –23 years  based on shared clinical decision -making , with a p referred age range  of 16–18 \nyears.  \nFor persons ≥2 months of age at increased risk, MenACWY vaccines are recommended for \nspecific medical conditions, some microbiologists, exposure  during an outbreak , travel to \n51 \n hyperendemic areas, and first -year college students. MenB vaccines are recommended for \npersons ≥10 years of age with certain medical conditions, some microbiologists, and those with \nexposure  during an outbreak . \nMenACWY vaccine products are interchangeable; while using the same brand is preferred, it is \nnot required for all doses in a series. In contrast, MenB vaccine products are not \ninterchangeable. MenB vaccines from the same manufacturer must be used for all d oses in the \nseries, including booster doses.  \nTwo MenABCWY vaccines are available in the U.S., one made by Pfizer (PENBRAYATM) and \nthe other by GSK (PENMENVY ). Both vaccines combine an existing MenACWY and MenB \nvaccine. They are both licensed as a two -dose series, with doses separated by six months for \npersons aged 10 –25 years. The Pfizer vaccine was licensed in October 2023, and the ACIP \nvoted on recommendations at its October 2023 meeting. The GSK vaccine was licensed on \nFebruary 14,  2025, and the ACIP will vote on recommendations for this vaccine today.  \nACIP recommended that the Pfizer pentavalent vaccine may be used when both MenACWY \nand MenB vaccines are indicated at the same visit for healthy persons aged 16 –23 years when \nshared clinical decision -making favors MenB vaccination, and for persons aged ≥10 years who \nare at increased risk for meningococcal disease.  \nDue to a lack of direct comparison data, the meningococcal vaccines work  group assessed the \nPfizer and GSK pentavalent vaccines separately. The MenACWY and MenB vaccine indications \nhave not changed with the availability of the pentavalent vaccines. ACIP previously expressed a \npreference to harmonize recommendations for the Pfiz er and GSK pentavalent vaccines unless \na vaccine -specific reason for differences exists.  \nImmunogenicity of meningococcal vaccines is measured using various assays. Traditional  \nhuman  serum bactericidal antibody  (hSBA ) assays use exogenous complement to assess \nseroprotection, seroresponse, or GMTs. For MenB strains, endogenous complement can be \nused to measure immune response against diverse serogroup B strains. However, a serologic \ncorrelate of protection exists only for serogroup C.  \nGSK’s pentavalent vaccine was assessed using three policy  questions.  \nPolicy question 1  \nShould the GSK pentavalent vaccine be included as an option for MenACWY/MenB vaccination \nin people currently recommended to receive both vaccines at the same visit?  \n– For example, 16 year -olds who decide to receive MenB vaccine based on shared clinical \ndecision -making  \nPolicy question  2 \nShould the GSK pentavalent vaccine be included as an option for people currently \nrecommended to receive MenACWY only?  \n–For example, 11 –12 year -olds  \nPolicy question  3 \nShould the GSK pentavalent vaccine be included as an option for people currently \nrecommended to receive MenB only?  \n– For example, during a serogroup B outbreak  \nFor ease of communication , the quadrivalent MenACWY vaccine is referred to as \"Q,\" the MenB \nvaccine as \"B,\" and the pentavalent vaccine as \"P.\"  Using this nomenclature,  the current ACIP \nrecommendation can be summarized as Q-QB-B (if MenB vaccine is included) or Q-Q (if it is \n52 \n not).  The work group supported  the use of GSK’s pentavalent vaccine as an option for \nMenACWY/MenB vaccination in people currently recommended to receive both vaccines at the \nsame visit (Q-P-B), but not for those currently recommended to receive only MenACWY (P -P) or \nMen B ( Q-P-P). \nDr. Schill ie then reviewed the updated EtR.  For public health problem, Dr. Schillie shared that \nmeningococcal disease incidence in the U.S. declined dramatical ly from 1996 to 2019, with \nfurther decreases in 2020 and 2021. This decline began before vaccine introduction. Since \n2022, however, cases have increased. Preliminary 2024 data show 503 cases, the highest \nincidence since 2013, at 0.15 per 100,000 population . The work group felt that invasive \nmeningococcal disease is of public health importance for all  three policy question s for the GSK \npentavalent vaccine.  \nThe work  group previously assessed the GSK pentavalent vaccine using BEXSERO  \nadministered on a 0 -, 2-month schedule as the comparator for the MenB antigens. BEXSERO  \nwas initially licensed as a two -dose series given at 0 and ≥1 month. The dosing schedule was \nrecently changed  to 0, 6 months, and because longer intervals improve immunogenicity, this \nraises the bar  for comparison .  \nThe clinical significance of the comparatively lower immunogenicity is uncertain, as no serologic \ncorrelate of protection exists for serogroup B disease. The work  group’s recommendations for \nuse of the GSK pentavalent vaccine remain unchanged, but the work  group believes ACIP \nshould consider the changes in comparative immunogenicity during its deliberations.  \nThe work  group’s previous synthesis presented to ACIP found the GSK pentavalent vaccine \nnoninferior  based on hSBA titers  to MenB on a 0, 2 month schedule  for three strains and on a 0, \n6 month schedule  for two strains. Noninferiority was not demonstrated for the PorA indicator \nstrain at either the 0 –2 month or 0 –6 month comparison. This strain is important as it represents \nthe vaccine's full outer membrane vesicle component and may impact cross -protection.   \nSuccess criteria for MenB protection using an endogenous complement hSBA assay were met \nagainst a broad range of strains, despite lower point estimates  compared to MenB on a 0, 6 \nmonth schedule. Findings regarding serogroups A, C, W, and Y immunogenicity and safety \nremain unchanged. The pentavalent vaccine had a similar safety profile to Men B, with slightly \nmore unsolicited adverse events than MenB ; there were more adverse events with the \npentavalent vaccine than were seen with MenACWY.  \nFinal  analyses of immunogenicity, as reflected in the package insert, were slightly different than \nwhat had been previously shared with ACIP ; Dr. Schillie reviewed a number of these differences  \nfor the committee.  Most differences were small  and t hey did not change the work group’s \noverall interpretation.  \nThe work group  previously determined that the desirable anticipated effects of the GSK \npentavalent vaccine were small for all three policy question s. This assessment remains \nunchanged. The work group  previously determined the undesirable effects to be minimal for \npolicy question  1 and small or minimal for the other policy question s. This assessment remains \nunchanged. For policy question  1, based on new immunogenicity data, a minority of the work \ngroup  now favors “favors comparison.” The overall certainty of evidence for short -term immunity \nwas rated as moderate or low for the three policy question s. This determination remains \nunchanged from the work group ’s previous assessment. The overall certainty of evidence for \nserious adverse events was rated as moderate or low for the three policy question s. This \ndetermination also remains unchanged from the work group ’s previous assessment.  \nFor resource use, Dr. Schillie shared that the expected price of the GSK pentavalent vaccine \nremains lower than the combined prices of the component vaccines. For policy question  1, the \n53 \n health outcomes are identical for the pentavalent vaccine and comparator, each preventing 91 \ncases of invasive meningococcal disease and 14 deaths compared to no vaccination. \nRegarding incremental cost -effectiveness ratios, as previously shared, QPB is cos t-saving \ncompared to the current strategy of Q -QB-B, saving $175 million with no difference in quality -\nadjusted life years. In the sensitivity analysis with updated price assumptions, QPB remained \ncost-saving. The work group  concluded that policy question  1 would be an efficient allocation of \nresources, but this varied for policy question s 2 and 3. The work group ’s assessment remains \nunchanged.  \nThe work group  continues to believe there is sufficient information to support a \nrecommendation. The work group  recommends the pentavalent vaccine for policy question  1, \ndoes not recommend it for policy question  2, and is divided on policy question  3. \nRecommending for policy question  1 aligns with the existing recommendation for the Pfizer \npentavalent vaccine.  \nPolicy question  1 typically involves one dose of the pentavalent vaccine and one dose of MenB \nto complete the MenB series. However, the studies evaluated two doses of the pentavalent \nvaccine. Recommendations for both pentavalent vaccines may be revisited in future adoles cent \nschedule discussions.  \nThe proposed vote language is:  \nACIP recommends GSK’s MenABCWY vaccine may be used when both MenACWY and MenB \nare indicated at the same visit*  \n*1) healthy persons aged 16 –23 years (routine schedule) when shared clinical decision -making favors administration of MenB \nvaccine and 2) persons aged ≥10 years who are at increased risk for meningococcal disease (e.g., because of persistent \ncomplement def iciencies, complement inhibitor use, or functional or anatomic asplenia)  \nDr. Talbot asked whether these products can be mixed and matched with the availability of the \nnew QPB, the existing version, and the potential for another in the future.  \nDr. Schillie responded that the manufacturer's MenB vaccine products remain non -\ninterchangeable. Only Pfizer products can be used if a Pfizer product was used to initiate the \nseries, and the same applies to the GSK product.  \nDr. Schec hter noted that he was under the impression there was more support for policy \nquestion  3 regarding the GSK product compared to past deliberations for the Pfizer product. He \nasked if that is the case and whether there is clarity on why that might be.  \nDr. Schillie stated that there was more support for the GSK product under policy question  3 \ncompared to policy question  2. However, the work group  ultimately favored policy question  1. \nThis position is primarily based on ACIP’s desire to harmonize recommendations between the \nPfizer and GSK pentavalent vaccines. She noted that policy question  3 would involve \nadministering additional ACWY antigens.  \nDr. Schec hter asked whether, in the coming years, it is likely or unlikely that real -world \neffectiveness data will become available, either from post -immunization infections or outbreak \nsettings.  \nDr. Schillie responded that she was unsure, noting that the rarity of the disease makes it \nchallenging to calculate real -world effectiveness. While some effectiveness data exist, they are \nlimited by small sample sizes.  \nDr. Barnett asked whether the work group considered a different recommendation for travelers \nto the meningitis belt of sub -Saharan Africa, given the reduced response to serogroup A, which \nis more common in that region.  \n54 \n Dr. Schillie explained that MenABCWY vaccines are typically not indicated for travel, as MenB \nalone is not recommended based on travel. Travel would not meet that criterion since the \npentavalent vaccine is intended for use when both MenB and MenACWY are in dicated. \nHowever, she acknowledged that reduced immunogenicity to serogroup A may be more relevant \nfor travelers. Still, the pentavalent vaccine would generally not be expected for travel -related \nuse. \nDr. Brewer asked how many vaccine types a pediatrician would need to stock to meet the new \nrecommendations under policy question  1, which includes the Q, P, and B components. He \nquestioned whether it would require stocking five different vaccines.  \nDr. Schillie clarified that the pentavalent vaccine is optional. Providers could continue stocking \none MenACWY product and one MenB product. If they wish to reduce the number of injections, \nthey could add the pentavalent product corresponding to the MenB m anufacturer they already \nuse. \nDr. Brewer asked whether providers should stock both MenB vaccines because the products \nare not interchangeable.  \nDr. Schillie responded that that would not be necessary, as providers could refer out the likely \nrelatively few patients in their practice needing the other brand.    \nDr. Zucker stated that, from a programmatic perspective, she supports harmonizing the \nschedule whenever possible, given its complexity. Unless there is a compelling reason to \ndifferentiate recommendations, she favored using the pentavalent vaccine when bot h \ncomponents are indicated and not allowing for alternative options.  \nDr. Asturias asked how the work group  reconciled maintaining shared clinical decision -making \nwith the potential cost savings of using a pentavalent vaccine. He noted that, given the \ncomplexity of the recommendations, practices may limit which vaccines they stock. He \nquestioned whether limitin g a potentially cost -saving pentavalent vaccine to a small subset of \nadolescents was appropriate or if he had misunderstood the approach.  \nDr. Schillie explained that the pentavalent vaccine is priced significantly lower than the \ncombined cost of the two -component vaccines. However, since it includes the MenB \ncomponent, its use remains subject to shared clinical decision -making. She noted tha t this \napproach may be revisited in the future as part of adolescent schedule discussions, but for now, \nthe MenB recommendation remains unchanged.  \nDr. Shaw asked about the consideration of noninferiority for the PorA antigen, noting that PorA \nexhibits substantial phase variation in expression and sequence variation within and across \nstrains. He wondered whether this is accurate and how much strain ma tching should be \nexpected for a highly polymorphic protein.  \nDr. Schillie explained that the PorA strain is important because it represents the vaccine's full \nouter membrane vesicle component. This strain did not show noninferiority in the exogenous \nassay. However, she emphasized that the post hoc analysis shown in the presentation \nsuggested similar  coverage for pentavalent and BEXSERO  for PorA  in U.S. strains , while the \ndata shown for the exogenous assay  may better represent New Zealand strain s and be less \nrelevant to the U.S. context.  \nDr. Kurilla, referencing the risk -based meningococcal vaccine recommendation slides, noted \nthat MenB is currently used on a limited, risk -based basis. He asked about a scenario in which a \ncollege student who previously received a pentavalent vaccine experi ences an outbreak at their \ncollege. He questioned whether a MenB vaccination would be recommended in that setting and \nhow likely it would be for the booster to match the original pentavalent br\n…[truncated]", "summary": "MEETING OF THE ADVISORY  COMMITTEE ON IMMUNIZATION  PRACTICES (ACIP)   APRIL 15-16, 202 5  MEETING SUMMARY   Trade names are used for identification purposes only and do not indicate endorseme nt.  2 TUESDAY : APRIL 15, 2025  WELCOME AND INTRODUCTIONS  Call to Order/Roll Call   Dr. Keipp Talbot (ACIP Chair) called the April 15, 2025, Advisory Committee on Immunization  Practices (ACIP) meeting to order.  Dr. Melinda Wharton (ACIP Executive Secretary) made  opening announcements about the…", "source_url": "https://www.cdc.gov/acip/meetings/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/minutes/summary-2025-04-15-16-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "minutes", "tags": ["acip", "cdc", "vaccines", "minutes"], "page_count": 117}
{"title": "agenda 2024 10 23 24 508", "content": "Final Agenda October 23-24, 2024\n8:00 Welcome & Introductions Dr. Keipp Talbot (ACIP Chair)\nDr. Melinda Wharton (ACIP Executive Secretary, CDC)\n8:20 Pneumococcal Vaccines \nIntroduction Dr. Jamie Loehr (ACIP, WG Chair)\nEconomic Analysis and public health impact of PCV use for adults aged \n≥50 yearsDr. Charles Stoecker (Tulane University)\nSummary of economic analyses of PCV use in adults aged ≥50 years Dr. Andrew Leidner (CDC/NCIRD)\nSummary of WG Interpretation of EtR and policy options on PCV use in \nadults aged ≥50 yearsDr. Miwako Kobayashi (CDC/NCIRD)\nClinical considerations for PCV use in adults Dr. Miwako Kobayashi (CDC/NCIRD)\n10:30 Break\n10:40 Influenza Vaccines\nIntroduction Dr. Jamie Loehr (ACIP, WG Chair)\nVaccine Effectiveness Update       Dr. Sascha Ellington (CDC/NCIRD)              \nInfluenza A/H5 update Dr. Tom Shimabukuro (CDC/NCIRD)\nInfluenza Vaccines VFC Resolution Dr. Jeanne Santoli (CDC/NCIRD)\n11:25 Chikungunya Vaccines\nIntroduction Dr. Edwin Asturias (ACIP, WG Chair)\nUpdate on chikungunya and chikungunya vaccines Dr. Susan Hills (CDC/NCEZID)\nVirus-like particle chikungunya vaccine Dr. Victoria Jenkins (Bavarian Nordic)\nWork group interpretation of vaccine data Dr. Susan Hills (CDC/NCEZID)\n12:10 Break\n12:40 COVID-19 Vaccines \nIntroduction Dr. Robert Schechter (ACIP, WG Chair)\nCOVID-19 vaccine uptake and implementation Dr. Georgina Peacock (CDC/NCIRD)\nCOVID-19 epidemiology Dr. Christopher Taylor (CDC/NCIRD)\nCOVID-19 vaccine effectiveness Dr. Ruth Link-Gelles (CDC/NCIRD)\nEconomic analysis of an additional dose of the 2024-2025 COVID-19 \nvaccineDr. Lisa Prosser (University of Michigan)\nEtR Ms. Lauren Roper (CDC/NCIRD)\nClinical considerations Dr. Lakshmi Panagiotakopoulos (CDC/NCIRD)\n3:35 Break\n3:45 Public Comment \n4:05 VOTES \nPneumococcal Vaccines Dr. Miwako Kobayashi (CDC/NCIRD)\nInfluenza Vaccines VFC Dr. Jeanne Santoli (CDC/NCIRD)\nCOVID-19 Vaccines Ms. Lauren Roper (CDC/NCIRD)\n4:35 Respiratory Syncytial Virus (RSV) Vaccines - Maternal/Pediatric\nIntroduction Dr. Helen Chu (ACIP,WG Chair)\nSafety and efficacy of clesrovimab Dr. Anushua Sinha (Merck)\nMaternal RSV vaccine safety Dr. Malini B. DeSilva (Health Partners Institute)\nWorkgroup considerations Ms. Danielle Moulia (CDC/NCIRD)\n5:30 RecessMEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)\nCenters for Disease Control and Prevention\nAtlanta, Georgia 30329  \nOctober 23-24, 2024\nWednesday, October 23, 2024\nFinal Agenda October 23-24, 2024\n8:00 Welcome & Introductions Dr. Keipp Talbot (ACIP Chair)\nDr. Melinda Wharton (ACIP Executive Secretary, CDC)\n8:10 Agency Updates CDC, CMS, FDA, HRSA, IHS, OIDP, NIH)\n8:30 Meningococcal Vaccines\nIntroduction Dr. Jamie Loehr (ACIP, WG Chair)\nEconomic analysis of GSK MenABCWY vaccine and comparison of \nGSK and CDC analysesDr. Xiaoyu Dong (CDC/NCIRD)\nGRADE/EtR for GSK MenABCWY vaccine Dr. Sarah Schillie (CDC/NCIRD)\nIntroduction to Bexsero interval and dosing label change Dr. Sarah Schillie (CDC/NCIRD)\nEtR for Bexsero interval and dosing change Dr. Sarah Schillie (CDC/NCIRD)\nSummary of work group considerations regarding Bexsero interval and \ndosing changeDr. Sarah Schillie (CDC/NCIRD)\n10:30 Break\n10:45 Respiratory Syncytial Virus (RSV) Vaccines - Adult \nIntroduction Dr. Albert Shaw (ACIP, WG Chair)\nModerna coadministration with high-dose influenza vaccine TBD (Moderna)\nPfizer immunogenicity in immunocompromised adults, coadministration \nwith COVID-19 and high-dose influenza vaccinesDr. Iona Munjal (Pfizer)\nGSK season 3 efficacy, immunogenicity in immunocompromised adults Dr. Susan Gerber (GSK)\nFDA self-controlled case series GBS update Dr. Patricia Lloyd (FDA)\nWork Group interpretations Dr. Michael Melgar (CDC/NCIRD)\n12:45 Break\n1:15 Immunization Schedules\nIntroduction to 2025 adult and child/adolescent immunization schedule Dr. Sybil Cineas (ACIP, WG Chair)\n2025 child and adolescent schedule revisions             Dr. Nanda Issa (CDC/NCIRD)\n2025 adult schedule revisions Dr. Patricia Wodi (CDC/NCIRD)\n2:15 Break\n2:25 Public Comment\n2:45 VOTES\nMeningococcal Vaccines Dr. Sarah Schillie (CDC/NCIRD)\nMeningococcal VFC Dr. Jeannie Santoli (CDC/NCIRD)\nImmunization Schedules Dr. Patricia Wodi (CDC/NCIRD)\n3:05 Break\n3:15 Human papillomavirus (HPV) Vaccines \nIntroduction Dr. Oliver Brooks (ACIP, WG Chair)\nIntroduction to policy consideration: reduced number of doses Dr. Lauri Markowitz (CDC/NCIRD)\nIntroduction to policy consideration: wording of the age for routine \nvaccination Dr. Ruth Stefanos (CDC/NCIRD)\nReview of the literature on HPV vaccination at ages 9-10 to increase \ncoverageDr. Sarah Brewer (CDC/NCIRD)\nWork group - next steps Dr. Carla DeSisto (CDC/NCIRD)\n4:30 Cytomegalovirus (CMV) Vaccine\nIntroduction: formation of the CMV vaccine workgroup Dr. Denise Jamieson (ACIP, WG Chair)\n4:40 Mpox Vaccine\nClade 1 Mpox Outbreak in Africa:   Situational Update Dr. Agam Rao (CDC/NCEZID)\n5:00 AdjournThursday, October 24, 2024\nFinal Agenda October 23-24, 2024\nAcronyms\nCDC Centers for Disease Control and Prevention\nCMS Centers for Medicare and Medicaid Services \nCORVD Coronavirus and Other Respiratory Viruses Division \nCOVID-19 Coronavirus disease 2019\nEtR Evidence to Recommendations Framework\nFDA Food and Drug Administration\nGRADE\nHRSA Health Resources and Services Administration\nHPV Human papillomavirus\nIHS Indian Health Service\nISO Immunization Safety Office\nNCHHSTP National Center for HIV, Hepatitis, STD and TB Prevention\nNCIRD National Center for Immunization & Respiratory Diseases\nNCEZID National Center for Emerging and Zoonotic Diseases \nNIAID National Institute of Allergy and Infectious Diseases\nOIDP Office of Infectious Disease and HIV/AIDS Policy\nRSV Respiratory Syncytial Virus (RSV) \nSARS-CoV-2 Severe Acute Respiratory Syndrome Coronavirus 2\nWG Work Group\nWHO World Health Organization\nVAERS Vaccine Adverse Event Reporting System\nVE Vaccine Effectiveness\nVFC Vaccines for ChildrenGrading of Recommendations Assessment, Development and Evaluation", "summary": "Final Agenda October 23-24, 2024 8:00 Welcome & Introductions Dr. Keipp Talbot (ACIP Chair) Dr. Melinda Wharton (ACIP Executive Secretary, CDC) 8:20 Pneumococcal Vaccines  Introduction Dr. Jamie Loehr (ACIP, WG Chair) Economic Analysis and public health impact of PCV use for adults aged  ≥50 yearsDr. Charles Stoecker (Tulane University) Summary of economic analyses of PCV use in adults aged ≥50 years Dr. Andrew Leidner (CDC/NCIRD) Summary of WG Interpretation of EtR and policy options on PCV…", "source_url": "https://www.cdc.gov/acip/meetings/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/agendas/agenda-2024-10-23-24-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "agendas", "tags": ["acip", "cdc", "vaccines", "agendas"], "page_count": 3}
{"title": "summary 2024 10 23 24 508", "content": "MEETING OF THE ADVISORY \nCOMMITTEE ON IMMUNIZATION \nPRACTICES (ACIP) \nOCTOBER 23-24 , 202 4 \nMEETING SUMMARY \nTrade names are used for identification purposes only and do not indicate endorsement. \n \n   \n \n  \n \n \n \n \n \n \n  \n  \n  \n \n   \n   \n    \n \n \n  \n \n \n   \n    \n  \n     \n \n \n \n  \n \n   \n  \n \n  \n \n \n  \n  \n \n  \n \n \n  \n \n   \n \n WEDNESDAY : OCTOBER 23, 2024 \nWELCOME AND INTRODUCTIONS \nCall to Order/Roll Call \nDr. Melinda Wharton (ACIP Executive Secretary) called the October 23, 2024, Advisory \nCommittee on Immunization Practices (ACIP) meeting to order. She made opening \nannouncements about the availability of presentation slides on the ACIP website, scheduled \noral public sessions, and the written public comment process. She reviewed conflict of interest \npolicies for ACIP members. She welcomed and introduced the new committee members: Dr. \nEdwin Asturias, Dr. Noel Brewer, Dr. Lin Chen, Dr. Helen Chu, Dr. Mini Kamboj, Dr. George Kuchel, and Ms. Charlotte Moser. She then conducted a roll call, which established a quorum . A \nlist of Members, Ex Officios , and Liaison Representatives is included in the appendixes at the \nend of this summary document. No COIs were identified for the first day of this meeting.  Dr. Bonnie Maldonado disclosed that she previously served as a Data Safety Monitoring Board \nmember for Pfizer ’s meningococcal vaccine trial s and as a site Principa l Investigator for Pfizer’s \npediatric COVID and maternal respiratory syncytial virus vaccine trials as well as AstraZeneca’s \nvaricella zoster vaccine trial. \nPNEUMOCOCCAL VACCINES \nDr. Jamie Loehr, Chair of the ACIP Pneumococcal Vaccines Work Group, introduced the \npneumococcal vaccines session. He pointed out that PCV21 is not PCV20 plus one additional \nserotype; PCV21 includes serotypes not included in previous pneumococcal vaccines and is \nmissing other serotypes previously included in earlier pneumococcal vaccines. Serotype 4 is not \nin PCV21 and may be relevant to specific populations. PCV20 included serotypes accounting \nfor 54% of cases of invasive pneumococcal disease (IPD) among adults 65 years of age and \nolder during the period 2018-2022, while PCV21 included serotypes accounting for 85% of \ncases . \nThere are several Pneumococcal vaccines in advanced stages of development. \n• 24-valent pneumococcal vaccines (Pn-MAPS24v, GSK; VAX- 24, Vaxcyte) \n• 31-valent pneumococcal vaccine (VAX -31, Vaxcyte) \nAdults currently recommended to receive a dose of pneumococcal conjugate vaccine (PCV) \ninclude: \n• Adults aged ≥65 years who have not received a PCV \n• Adults aged 19– 64 years with certain underlying conditions or risk factors who \nhave not received a PCV \n• Certain adults who have received PCV13 but have not received PCV20 \nPCV21 was developed to target pneumococcal serotypes that commonly cause disease in \nadults.  The manufacturer currently does not have plans to seek an indication for routine PC21 \nuse in infants. However, they will seek an indication for the use of PCV21 in children 2-18 years old with a risk condition for which the re is a Phase 3 trial currently in progress. The work group \ndoes not expect PCV21 to offer similar indirect protection from its additional serotypes that were observed from PCV7 or PCV13 use in children. \n2 \n \n    \n   \n   \n  \n \n  \n \n \n \n     \n \n  \n   \n  \n  \n \n  \n \n   \n \n     \n  \n   \n  \n  \n \n \n \n \n   \n  \n     \n    \n     \n  \n \n \n \n \n  In June 2024 the work group agreed that available evidence supports PCV21 use for adults \ncurrently recommended to receive a PCV but could not reach a consensus on whether the age-\nbased recommendations for PCV21 should be lowered from ≥65 to ≥50 years. Most work group \nmembers believed there was insufficient evidence to support lowering the age-based recommendation for other recommended PCVs, specifically PCV15 and PCV20. \nAt the June ACIP meeting, the committee requested that the work group come back to the committee with a summary of data on whether the recommended age should be lowered to ≥50 \nyears for all PCVs (not just PCV21) at today’s meeting, as the committee felt that there was not \nenough data to decide on PCVs other than PCV21 at that time. Another request was to s hare \ndata on the possible consideration of discontinuing the recommendation for PPSV23 in the future. \nThe initial policy options considered by the work group were \n1. Lower the age-based recommendations for all PCVs to age ≥50 years \n2. Lower the age-based recommendation for all PCVs to age ≥60 years or age ≥55 years \n3. Lower the age-based recommendation to age ≥50 years but only for PCV21 \n4. Shared clinical decision- making for PCV use for adults aged 50– 64 years who currently \ndo not have a risk -based vaccine indication \n5. Status quo (i.e., age-based at age ≥65 years, risk-based for younger adults) \nThe final proposal from the work group was to l ower the age-based recommendations for all \nPCVs to age ≥50 years . The majority supported this option after a targeted discussion of the \npolicy question.  An additional dose may be needed in the future to avoid increased \npneumococcal disease burden in older adults . Several key uncertainties remain: indirect effects \nfrom new pediatric pneumococcal vaccines ; the duration of protection from adult vaccination; \nand the impact of new higher -valency vaccines for adul ts. Key factors in the work group \nproposal were higher pneumococcal disease rates in Black adults, with an earlier peak; many \nadults 50-64 years of age already have an indication for risk -based pneumococcal vaccination; \nan age-based recommendation is more likely to improve uptake than is a risk -based \nrecommendation; it will be easier to implement a uniform recommendation across all PCVs ; \nPCV21 had a more favorable health economic profile than PCV20, although both would be \nexpected to improve health outcomes; and the serotype compositions of PCV20 and PCV21 are quite different. \nDr. Charles Stoecker (Tulane University) discussed PCV use's economic analysis and public \nhealth impact for adults aged ≥50 years . The request to the work group was to evaluate the \ncost-effectiveness of an age-based recommendation for PCV20 or PCV21 in adults younger \nthan 65 years of age. The motivation is to get higher vaccine uptake among adults with \nunderlying risk conditions , by changing from a risk-based to an age-based recommendation. \nAdditionally, this may lead to higher pneumococcal vaccine uptake among the general \npopulation. The model evaluated the program's cost and savings and look ed at changes in \ndisease, medical, nonmedical, and work productivity costs. The population wa s a cohort of \nabout 4 million 50-year -olds. Separate categories were created for immunocompromised \nindividuals (IC), individuals with chronic medical conditions (CMC), and others or the general \npopulation that are not IC or have CMC. \n3 \n \n   \n \n \n \n \n  \n \n \n \n  \n \n  \n   \n \n \n \n \n  \n \n \n    \n \n  \n \n  \n  \n \n  \n  \n \n \n \n  \n    \n  \n \n \n Moving Strategies and Adding Strategies were used to evaluate the study question. The Moving \nStrategies will move the age-based recommendation from 65 to 50 years of age. This will shift \nthe disease burden from younger adults to older adults, leaving older adults less protected. The Adding Strategies will add a vaccination at age 50 in addition to age 65. This will maintain \nprotective benefits for older adults from the current age-based recommendation. \nThe first Moving Strategy the work group evaluated was an intervention of PCV20 at age 50 \ncompared to PCV20 at diagnosis of CMC/IC and PCV20 at age 65 (current recommendation). \nThe second Moving Strategy was an intervention of PCV20 at age 60 compared to PCV20 at \ndiagnosis of CMC/IC and PCV20 at age 65 (current recommendation). The first Adding Strategy \nevaluated was an intervention of PCV20 at ages 50 and 65 compared to PCV20 at diagnosis of CMC/IC and PCV20 at age 65 (current recommendation). The second Adding Strategy evaluated an intervention of PCV20 at ages 60 and 75 compared to PCV20 at diagnosis of \nCMC/IC and PCV20 at age 65 (current recommendation). The above comparisons were \nrepeated for PCV21. \nThe PCV20 and PCV21 vaccines are estimated to cost approximately $300, with an additional \n$75 for administrative and other costs. Two scenarios will be evaluated for waning. There will be \nno waning for the first 5 years in either scenario. The first will wane to 0 by 15 years, and the \nsecond will wane to 0 by 20 years. \nThe model also includes the impact of herd effects of PCV20 in children. In year 1, the disease \nwill be reduced by 25%, with 75% of the disease remaining for the serotypes in PV20. In year 6, 85% of adult disease will be gone due to PCV20 in children. In years 7+, there is no fu rther \ndecline and will maintain 15% remaining disease seen in year 6. Limitations include uncertainty around waning and herd effects and pneumococcal disease trends. Sequelae from IPD were not modeled explicitly, and disruption from changing pneumococcal schedules was not \nmodeled. \nMoving strategies resulted in increased net cases. While lower cases and deaths were seen in \npeople ages 50-64, increased cases and deaths were seen in adults ≥65 years of age. It does \nhave a lower cost, and these results hold under longer vaccine-waning scenarios and scenarios without herd immunity from the childhood program. \nAdding a second age-based vaccination increased the cost per quality -adjusted life year ( QALY ) \ncompared with current recommendations. The incremental cost-effectiveness ratio s (ICERs ) \nranged from $50k/QALY to $500k/QALY. The ICERs are consistently lower for PCV21 \nrecommendations than that of PCV20. Economic efficiency is improved in PCV20 and PCV21 when no herd effects are included. The changes in $/QALY are more significant in PCV20. However, this change is insufficient to make PCV20 more efficient than PC V21. Assumptions \nsurrounding vaccine waning are minimally impactful on ICERs because the waning is extended in both the intervention and comparison strategies. Vaccination at later ages is more \neconomically efficient. \nDr. Andrew Leidner (CDC/NCIRD) summarized three economic analyses on the use of PCVs \namong 50-64-year -old adults in the U.S. The main objective of cost-effective analysis (CEA) is \nto calculate an ICER. The ICER value is the cost per outcome and summarizes the difference in \nvalue between the two vaccination strategies. The difference in cost of the two strategies is divided by the difference in outcomes to get the ICER. In this case, the two strategies are PCV vaccination intervention at age 50-64, and the comparator is the current set of PCV recommendations. \n4 \n \n  \n \n \n  \n    \n \n \n  \n \n \n \n \n   \n  \n  \n \n   \n  \n \n \n \n  \n \n \n   \n \n \n \n \n \n \n  \n  \n \n  \n  Economic models of vaccination can be considered calculations that summarize many aspects \nof a disease vaccine into a single economic value. The economic model inputs include vaccine \nefficacy, disease burden, fatality rates, and cost s. These factors contribute to the estimated \nICER. If the underlying factors are uncertain, the estimated ICER can have a range to reflect \nthat uncertainty. \nAs a reminder, the policy question being considered by these models is “Should a single dose of \nPCV be recommended for all PCV -naïve adults aged 50-64 years?” \nAmong the “Moving” comparisons in the models, the intervention is age-based vaccination at \nage 50, and the comparator is current recommendations for PCV. In this comparison, the \nintervention increases PCV coverage among 50-64-year -olds and reduces coverage among \nadults ≥ 65 years of age. The results from the Tulane-CDC and Pfizer models indicated that this \ncomparison would likely increase the burden of disease overall and shift the burden of disease from adults in their 50s to older adults in their 60s and 70s. There was an increased number of cases, hospitalizations, and deaths. Also note that in this “moving” comparison, the intervention \nhas 0% vaccination coverage for adults ≥65. \nAmong the “Adding” comparisons in the models, the intervention is age-based vaccination at \nages 50 and 65 years , and the comparator is current recommendations for PCV. The “Adding” \ncomparison allows for a more direct estimate of the impacts of expanding coverage to adults \naged 50-64. This comparison also presumes that older adults (65 and up) would not be left \nwithout disease protection if the age -based recommendation is lowered. \nAcross the main results of the Tulane-CDC and Merck models, looking at age-based use at age 50 and 65 compared to the current recommendations, the cost per QALY for PCV21 ranged from $130,000 to $430,000. Across the main results of all three models, the cost per QALY for \nPCV20 ranged from $56,000 to $880,000 per QALY . Across all available models, there’s a \nbroader range for PCV20 than for PCV21; this is partially due to 3 models being assessed \nPCV20 vs only two models that assessed PCV21; this is also due to the impact of indirect effects, which has a larger impact on PCV20 values than PCV21 values. The Tulane-CDC \nICERs tended to be lower than ICERs from the Merck model and were higher than ICERs from \nthe Pfizer model. The Tulane-CDC and the Merck models assessed both vaccines; in those \nmodels, PCV21 was less expensive than PCV20. \nScenarios with estimated higher vaccine effectiveness and longer duration of protection (>15 years) had lower costs per QALY. Across the Tulane-CDC and Merck model, for PCV21, the \nICERs range from $117,000 to $200 ,000 per QALY. Across all three models, for PCV20, the \nICERs range from $62,000 to $420,000 per QALY. Note that the lowest estimates for PCV20 \nwere from the Pfizer model. Indirect effects are another highly uncertain and impactful input in these models. In these scenarios, when indirect effect assumptions are reduced, there will be a \nmore significant disease burden in the adult population; this greater disease burden leads to \nbetter values or lower ICERs across all models. \nThe work group also considered two other models: the Merck health equity model and the \nPittsburgh model. The Merck team submitted a separate health equity modeling analysis that \nused the Atkinson index to quantify inequality across Black and non-Black populations, with and \nwithout 50- to 64-year -old PCV vaccination. Their model concluded that 50- to 64-year -old \nvaccination would reduce health inequality (or improve health equity). The Pittsburgh model was summarized in the meeting last June. This model also focused on the value of PCV use among \nBlack and non-Black population groups, and this model estimated equity benefits associated with 50- to 64-year -old PCV vaccination. \n5 \n \n   \n \n \n \n \n \n   \n \n \n   \n  \n \n \n \n  \n \n  \n \n  \n \n \n  \n \n    \n \n \n \n  \n \n \n \n  \n  There is substantial uncertainty and limited data available for several key model inputs, \nincluding vaccine effectiveness and duration of protection; indirect effects from pediatric PCV20 \nuse; and the impact on vaccine coverage of the proposed age-based recommendation. Additional limitations include the future epidemiology of serotype 4 and 19F, the impact of supplemental PCV doses, the availability of new higher -valency vaccines in coming years, and \nimplementation challenges possibly associated with changing the schedule, which were not considered in the models. \nIn summary, using the “adding” approach, age-based vaccination at 50 years would improve \nhealth but was not cost -saving. Estimated results had a broader range in value for PCV20 than \nPCV21 because three models, not just two, assessed PCV20. Finally, in the two models that assessed both vaccines, the estimated costs per QALY were lower for PCV21 than for PCV20. \nDr. Chu inquired why the Pfizer model assumed 36% VE compared to 0% after the waning period and whether there w ere data to support it. \nDr. Leidner replied that t he assumptions made in the models are based on expert opinion. To \nclarify, the Tulane-CDC models showed that vaccine effectiveness (VE) declined linearly from \nfive years to zero by the fifteenth year. In contrast, the Pfizer model exhibited a parabolic \ndecline, gradually decreasing each year. By year 15, the effectiveness was at 36%, and it \ndropped to 0% in year 16. \nDr. Talbot asked which studies used to determine the 15-year duration. \nDr. Kobayashi explained that there are insufficient data to determine the appropriate duration for \nthe period in question. The decision is based on methodologies used in other studies where \nassumptions about duration and protection were necessary. More reliable data will be available \nin the future. \nDr. Talbot asked whether any modeling was done based on a 20-year protection period to see if \nthe model would change. \nDr. Leidner confirmed that all three models varied the duration of protection. The Tulane-CDC and Merk models included a 20-year waning period. When there is a more extended protection period, the ICER s decrease. This decrease is not as large as seen with the herd effects. \nDr. Kobayashi noted that the group explored data from other conjugate vaccines, including meningococcal vaccines. It is essential to recognize that the severity of the diseases can differ, so we cannot automatically apply findings from one vaccine to another. Additionally, studies indicate that the duration of protection provided by meningococcal conjugate vaccines is not \nvery long, typically waning within ten years. While the dosages given to children differ from \nthose administered to adults, some pediatric studies have shown a gradual decline in protection \nwithin approximately seven years. Consequently, we assume that the protection period may not \nextend significantly beyond this estimate, although we acknowledge the uncertainties. \nDr. Talbot mentioned a group of adults who received the PCV13 vaccine, and it would be \ninteresting to review the serology data on this group since it has been 10 years. \nDr. Kobayashi confirmed that the group would like to explore this group in the future. \n6 \n \n  \n \n  \n \n \n  \n \n \n \n \n \n  \n   \n \n   \n \n \n  \n   \n \n    \n \n \n   \n \n  \n  \n   \n  \n \n  \n   \n \n  \n \n   \n    \n  \n \n \n \n   \n    \n  Dr. Shaw inquired whether considerations for post-infection care, like the need for long-term \ncare, a skilled nursing facility, or increased disability, were considered in the models. \nDr. Leidner confirmed that the Merck model included a disability state following IPD episodes, \nand the Pittsburgh model included a disability state following a small percentage of IPD episodes and nonbacteremic pneumonia episodes. \nDr. Miwako Kobayashi (CDC/NCIRD) presented the Evidence to Recommendations (EtR) Framework for the policy question, “Should a single dose of PCV be recommended for all PCV -\nnaïve adults aged 50-64 years?” The seven EtR domains are public health problem, equity, benefi ts and harms, values, acceptability, resource use and feasibility. \nFor public health importance, Dr. Kobayashi shared that after PCV13 was recommended for children in 2010, IPD rates decreased in children and older adults through the indirect effects of \nPCV13 use in children. Subsequently , the incidence of IPD in adults aged 50-64 years has been \nhigher than that in children <5 years of age. It’s worth noting that although PCV13 was \nrecommended for all adults aged 65 years and older in late 2014, this intervention had minimal \npopulation-level impact, leading to the discontinuation of this age-based recommendation in \n2019. The IPD mortality rates in adults aged 50– 64 years and 65 years of age and older have \nbeen the highest across all age groups. Over time, the IPD mortality rate in adults ≥65 years \nhas become closer to that in adults aged 50– 64 years. Nearly 90% of adults ages 50 -64 with \npneumococcal disease had at least one condition that currently qualifies for a risk -based \npneumococcal vaccine indication. Data show that the success of the pediatric pneumococcal \nvaccine pro gram increased the relative burden of pneumococcal disease in adults aged 50– 64 \nyears, especially in those with risk conditions. The work g roup agreed that pneumococcal \ndisease is of public health importance. \nEquity was a key consideration among the work g roup. About 32 to 54% of adults aged 50-64 \nyears have a self-reported condition with risk -based pneumococcal vaccine indications with a \nbroader range across race and ethnicity groups compared with adults ≥65 years of age. When \ncompared to non-Black adults, Black adults' IPD rates peak at age 55-59 years, with higher \nrates in all age groups than are seen among non-Black adults, in whom rates steadily increase \nwith increasing age. The IPD rates for Black adults aged ≥50 years exceed the average IPD \nrate for all adults ≥65 years of age. In a hypothetical scenario that applied the current risk -based \nvaccine coverage by race for adults 19- to 64 years and age -based vaccine coverage by race \nfor adults 65 years of age and older, the rates of non-PCV13- type IPD in American Indian (AI), \nAlaska Native (AN), and Black adults remain higher than the population average across all racial groups with either PCV20 or PCV21. Another scenario applied the current vaccine \ncoverage for adults ≥65 years of age by race to adults ≥50 years of age and current risk -based \nvaccine coverage by race to adults 19- to 49 years of age. IPD incidence in AI, AN, and Black \nadults decreased more compared with scenario 1 with either PCV20 or PCV21 ; however, the \nrate decreased below the population average for Black adults in the PCV21 scenario only. Therefore, racial disparities are expected to remain. The Work Group interpretation was that recommending PCV for all PCV -naïve adults aged 50– 64 years of age would probably increase \nhealth equity. \nTo inform the benefits and harms domain, the Work Group updated its systematic literature \nreview to include 6 PCV15 trials, 3 PCV20 trials, and 7 PCV21 trials. Immunogenicity data from \nthese trials was used to inform the benefit domain. The overall conclusions on immunogenicity remain unchanged. PCV15 met the noninferiority criteria for all serotypes shared with PCV13 \n7 \n \n    \n \n \n  \n    \n \n     \n  \n \n  \n  \n  \n \n \n \n \n \n  \n \n  \n \n \n \n   \n   \n    \n \n   \n   \n \n \n \n   \n  \n \n     \n  \n \n \n while having statistically significantly greater responses to the additional serotypes 22F and 33F. \nPCV20 also met the noninferiority criteria for all PCV13 serotypes. Compared to PPSV23, \nPCV20 met the noninferiority criteria for six out of seven non-PCV13 serotypes, except serotype \n8. PCV21 met the noninferiority criteria when compared to PCV20 for all ten shared serotypes \nand had statistically significantly greater response to ten out of eleven serotypes unique to PCV21; the exception was serotype 15C. The work g roup believed that the anticipated benefits \nof the intervention were of moderate magnitude. However, it's important to note that data which directly address the outcomes specified in the PICO question are unavailable for these newer \nvaccines. \nThe conclusions from safety data from the PCV clinical trials also remained unchanged. No \nvaccine -related serious adverse events were reported for PCV15 and PCV20, but two were \nreported among PCV21 recipients. Post-licensure PCV20 safety data showed a potential \nGuillain -Barré s yndrome (GBS) signal for PCV20 in the Vaccine Adverse Event Reporting \nSystem ( VAERS ). In an updated analysis of Medicare data through May 2024 conducted by the \nFDA, there was a GBS signal in sequential monitoring for the primary definition but not for the alternate definition or when adjusted for positive predictive value; there is significant uncertainty \nbecause of the small number of GBS cases observed.  CDC and FDA will continue to monitor \npost-licensure PCV safety. Given the uncertainties, the work group felt that the undesirable \nanticipated effects of PCV vaccination were minimal despite the updated PCV20 pos t-licensure \nsafety data from the FDA. Weighing the desirable and undesirable anticipated effects, the work \ngroup believed that supports a recommendation for PCV for all PCV -naïve adults aged 50 – 64 \nyears compared with the current risk -based recommendation. \nFor the values domain, the work group was split between “yes” and “probably yes” regarding the \ntarget population's feeling that desirable effects are large relative to undesirable effects. A third of the members responded “don’t know.” Members with experience serving underserved populations wi th many underinsured or self-pay individuals noted that these groups can be \ncomfortable with pneumococcal vaccines if the benefits are clearly explained. When asked, “Is \nthere important uncertainty about or variability in how much people value the main outcomes?” \nthe work g roup’s interpretation was “Probably not important uncertainty or variability.” \nThe work g roup felt that it is acceptable to recommend PCV for all PCV -naïve adults aged 50– \n64 years . This is supported by a presentation on the Merck -funded healthcare provider surveys \nat the June ACIP meeting. These findings showed challenges with risk -based vaccine \nrecommendations and that surveyed providers supported lowering the age-based recommendation to age 50 years . \nFor resources, the majority of the work g roup responded either “probably yes” or “yes” that PCV \nuse for PCV -naïve adults aged 50-64 years was a reasonable and efficient allocation of \nresources. A minority portion of the members said, “probably no.” Those who said “probably no” expressed concerns about the less favorable economic analysis findings for PCV20 than \nPCV21. Some work group members felt that improved vaccination coverage among those with \nrisk-based pneumococcal vaccine indications could diminish the need for broader age-based vaccination. However, insufficient success of this approach was acknowledged. Some work \ngroup members believed the decision varies when considering projections over the next 15 \nyears. \n8 \n \n    \n \n \n   \n \n \n \n  \n  \n \n \n \n \n  \n  \n  \n  \n \n  \n \n \n \n \n \n \n  \n \n   \n \n  \n \n \n \n  \n  \n \n  \n \n \n \n Dr. Kobayashi shared that the work g roup reached a combined majority of “probably yes” and \n“yes” regarding the feasibility of implementing PCV for all PCV -naïve adults aged 50 -60. \nVaccine coverage tends to be lower in younger adults, even with an age-based \nrecommendation. However, with risk -based indications, pneumococcal vaccine coverage was \ndisproportionately lower in adults aged 50– 64 years compared with coverage in adults 65 years \nof age and older. Some Work Group members believed that age-based recommendations are \ngenerally easier to implement than risk -based and that the lower vaccine coverage in younger \nadults is likely due to multiple factors, such as healthcare access, perceived risk of disease, or \nbenefits from vaccination. W ork g roup members agreed that having a different age-based \nrecommendation by vaccine product would be more challenging to implement. At the same time, \nvariability in health insurance coverage might keep PCV20 as the only practical option for some individuals in the short term since PCV21 is new. \nFactors supporting lowering the PCV age-based recommendation that the work group \nrecognized were the following: \n• The relatively high burden of pneumococcal disease in adults aged 50– 64 years, \nparticularly among those with risk conditions \n• Potential for improved vaccine uptake through an age-based recommendation \n• Potential to reduce pneumococcal disease incidence in demographic groups \nexperiencing the highest burden \n• Projected health benefits from economic models despite increased net costs \nThe work g roup also identified a number of potential implications for lowering the age-based \nrecommendations for all PCVs.  There were significant concerns about the cost of lowering the \nage recommendation for both PCV20 and PCV21 when considering overall health benefits to \nsociety. Variability in health insurance coverage might keep PCV20 as the only practical option \nfor some individuals in the short term, given that PCV21 is a newer vaccine, but the Work Group agreed that it would be challenging to implement different age-based recommendations by \nvaccine . \nThe work g roup highlighted several uncertainties that could impact future policy decisions , \nincluding the duration of protection from a dose of PCV in adults ; the magnitude of the indirect \neffects of pediatric PCV15/20 vaccination; and the impact of higher -valency vaccines which are \nunder development. \nDespite these uncertainties and concerns, most of the work group believed that recommending \na single dose of PCV for all PCV -naïve adults aged 50– 64 years would probably result in \ndesirable consequences outweighing undesirable consequences in most settings. The work group members who disagreed with the recommendation had concerns with the higher \ncost/QALY gained for PCV20 compared to PCV21, the uncertainties regarding the impact of \npediatric PCV use, and concerns about the implications of a broad recommendation given that \ndifferent serotypes are included in PCV20 and PCV21. \nThe work group agreed to propose the following policy option: \nACIP recommends a pneumococcal conjugate vaccine for all PCV -naïve adults aged \n≥50 years. \n9 \n \n  \n    \n \n \n \n  \n \n  \n   \n \n \n   \n \n    \n   \n \n \n \n   \n \n \n  \n     \n    \n \n \n \n \n \n  \n  \n  \n \n   \n  \n \n \n  \n  \n   \n \n  \n \n \n  \n \n \n   \n \n Dr. Talbot requested clarification on whether, if we move forward with a recommendation for \nadults older than age 50 years , there would be an evaluation of whether a second dose is \nrequired. \nDr. Kobayashi confirmed that there is insufficient evidence to recommend when precisely the \nsecond dose should occur. Therefore, today’s policy option will not include a second dose. \nDr. Schechter asked what vaccination coverage rates were used in the hypothetical scenarios \nthat were presented and whether they were the same across different race/ethnic groups.  Dr. Kobayashi explained that these analyses used observed vaccine coverage data from the \n2021 Behavioral Risk Factor Surveillance System (BRFSS) for age- and risk -based \nrecommendations for each group. For simplicity, they also assumed that all vaccine-type \ndiseases would be prevented. Thus, the reduction in disease predicted is due the observed \nvaccine coverage by racial group and serotype distribution in each racial group. \nDr. Chu asked for clarification that the recommendation is to move the age recommendation \nfrom 65 to 50 years of age. However, in the “moving” strategy, the disease burden rises from the \nyounger population to the older, if a second dose is not recommended at age 65. \nDr. Kobayashi responded that if no future vaccination coverage is offered, that is a potential risk. \nHowever, as mentioned during the economic model presentations, it is unlikely that adults will \nonly have an opportunity to get vaccinated at age 50. If the age-based recommendation is \nlowered, adults will likely be vaccinated at older ages. The work g roup also does not know what \nrecommendations will made in the future for new vaccines that may come. Because of these \nuncertainties, the team would like to reevaluate this in the future. \nDr. Chu inquired whether the group had data by race on uninsured 50- to 64-year -olds who \nwould not be able to receive the PCV21. \nDr. Kobayashi estimated that about 10% of adults in the 50- to 64 year old age group do not \nhave insurance coverage, and this value decreases in adults 65 years of age and older. These \ndata are not available for this age group by race. \nDr. Brewer asked whether the vaccine effectiveness remains the same at ages 50 and 65 years \nand how the work g roup decided on the vaccination at age 50. He suggested that using an \nexisting vaccination age from the schedule might complicate vaccinating at that age. \nDr. Kobayashi noted evidence suggesting that vaccine effectiveness may be lower in older \nadults than younger adults. The work group considered age thresholds of 55 and 60 but \nultimately selected age 50 because the incidence of IPD is elevated in Black adults beginning at \nage 50 years with a peak at 55-59 years. The age of 55 was not chosen since it did not align \nwith existing vaccination recommendations, which raised concerns about implementation. \nDr. Shaw asked if guidance would be provided to practitioners treating populations with a higher \nprevalence of serotype 4 disease since PCV21 does not include this serotype. \nDr. Kobayashi does not have updated data for populations observing a higher prevalence of serotype 4 disease. This guidance is captured in an MMWR published in September 2024. When available, updated data will be shared. \n10 \n \n  \n \n \n \n  \n \n     \n      \n \n  \n    \n \n \n  \n \n  \n \n \n     \n   \n  \n \n \n  \n   \n  \n   \n  \n \n \n  \n \n \n  \n \n \n \n \n \n  \n \n \n \n    \n \n \n \n  \n Dr. Asturias asked what proportion of other medical conditions were diagnosed at the time of the \npneumococcal infection. \nDr. Kobayashi stated that this information is unavailable, but people may have gotten sick and \nhad undiagnosed risk conditions. \nDr. Brooks asked whether data w ere available on the vaccination status of those with risk \nfactors who were hospitalized with pneumococcal disease in the age group 50- to 64 years. \nDr. Kobayashi responded that vaccination history is not available in these data sources for \nindividuals with risk conditions but that her team would like to explore this in the future. \nDr. Maldonado commented on the issue of access. Messaging needs improvement for the 50-\nto 64-year -old group. Referring to COVID-19 vaccination , individuals with underlying conditions \nhad difficulty getting documentation to provide to pharmacies for additional off-label doses of \nvaccines. She called for action for these groups and studies to see why these individuals are missing vaccinations. \nDr. Loehr clarified that the work g roup did not intend to penalize individuals over age 65 by \nrecommending the vaccine dose at age 50. If waning immunity is as expected, the work g roup \nfelt that an additional dose would be needed 15 years after the initial dose. Currently, these data \nare unavailable, but this issue will be studied over time. He also mentioned that if there is a high \nprevalence of serotype 4 in a community, clear guidance will be provided recommending PCV20 \nover PCV21 or a vaccination for serotype 4 if any new options become available. He \nemphasized that most members of the work g roup favored lowering the age for all PCVs to age \n50 for equity reasons. However, Dr. Loehr stated that as an individual ACIP member he \ndisagrees and believes that only the age recommendation for PCV21 should be reduced to age 50. The work g roup decided to lower the age for all PCVs to simplify the vaccination schedule \nfor physicians. Dr. Loehr disagrees with this decision due to the differences in cost \neffectiveness , as PCV20 has a higher cost per QALY than PCV21 when the age is lowered to \nage 50. He believes that PCV21 is a better vaccine because it covers more serotypes. Despite \nhis personal disagreement, he formally made a motion to recommend that a PCV be \nadministered to all PCV -naïve adults aged 50 years and older. \nDr. Cineas seconded the motion. \nDr. Talbot commented that vaccinating at age 50 and again at age 65 is a win because it means \nadults have had a healthy life and have not passed away before their grandchildren. \nDr. Brewer stated that the implementation argument has not yet persuaded him and that \nhe cannot support this for PCV20. \nDr. Brooks emphasized that there are seven domains of EtR and questioned whether problems \nin just one domain should be sufficient to influence a vote on the proposed policy option. He believes the positives in the other domains outweigh the negatives in the areas of concern. \nDr. Shaw reminded the group that even with the proposal to lower the age-based \nrecommendation to age 50 for PCV21, an exception will still need to be made for prevention of \nserogroup 4 disease in at-risk individuals. \n11 \n \n     \n \n \n \n \n \n   \n \n \n \n    \n    \n     \n      \n  \n \n  \n \n \n   \n  \n \n \n \n    \n \n \n  \n \n   \n \n \n  \n \n  \n \n \n \n  \n \n \n \n Dr. Loehr confirmed that serogroup 4 will be addressed in clinical considerations. He also \nemphasized that there is a difference in how different members’ values are reflected in the \npriorit y they place on different EtR domains. He does, however, respect the work g roup’s \ndecision. \nDr. Jamieson mentioned that, along with cost-effectiveness, another issue is that PCV21 \nserogroup coverage is better for most adults. It seems that this can be handled in clinical \nconsiderations. This may mean a recommendation for 50 and above, but with clinical \nconsideration, PCV21 may be better in some cases based on serogroup coverage. \nDr. Zimmerman commented on behalf of the Association for Prevention Teaching and Research, \nstating the group was in support of lowering the age of routine vaccination to 50 years due to the benefits on health equity and to better protect individuals with high-risk conditions aged 50-\nto 64 years because risk-based recommendations result in lower vaccine coverage than age-\nbased recommendations. There is a large burden of pneumococcal disease in persons under 65 \nyears of age with high-risk conditions and the highest rates for pneumococcal disease in Black \nAmericans are seen among those under 65 years of age. A published decision analysis showed \nthat PCV21 at age 50 and again at age 65 will result in a 15% decrease in IPD cases in Black \nAmericans and a 14% decrease in other populations. \nDr. Goldman favored lowering the age recommendation for vaccination because it would \nimprove implementation and benefit the patients. He reiterated that PCV2 1 is very different from \nPCV20 . He shared that he is concerned with lowering one, not the other, because \nrecommendations would differ for those in this age group with and without underlying medical \nconditions. It is essential to be concise and clear on who should be vaccinated between 50 and \n64, especially among those with other medical conditions. \nDr. Richard Haupt (Merck ) expressed strong support for the recommendation and underscored \nthe imperative of this vote for improved adult pneumococcal vaccine utilization and, more \nimportantly, health equity. A vote to expand the age-based recommendation improves access to \nthe benefits of pneumococcal vaccination. It provides opportunities to reduce persistent disparities in pneumococcal disease risk that current recommendations have not addressed. He also noted that Merck has very high payer coverage from both commercial and Medicare Advantage plans for PCV21, licensed in June. The vast majority have already covered PCV21. \nDr. Luis Jodar ( Pfizer ) stated that despite the different compositions, Pfizer supports the ACIP \nrecommendation to use any currently available PCVs for all adults ages 50 and older. In the \ncase of PCV20, this is supported by the burden of IPD and pneumococcal pneumonia caused by the 20 serotypes which remains a public health concern, which is especially important for \nserotypes unique to PCV20, including serotype 4, which has been increasing in the U.S. and \nglobally with a focus on disadvantaged populations. Pfizer recommends the coexistence of both \nPCV21 and PCV15 followed by PCV23 and PCV20 in the population, which will allow a greater \nchoice and less complexity of recommendations and increase equity and improve \nimplementation. \nDr. Kobayashi then provided an overview of proposed c linical considerations for implementation.  \nThe proposed language is as follows: \nA single dose of PCV (PCV15, PCV20, or PCV21) is recommended for all adults aged \n≥50 years and for adults aged 19– 49 years with certain underlying conditions or risk \nfactors* who have not received a PCV or whose vaccination history is unknown. \n12 \n \n  \n \n \n \n \n  \n \n \n \n \n \n \n \n \n \n \n \n \n  \n \n   \n \n  \n    \n \n \n    \n  \n \n  \n  \n    \n \n  \n  \n \n    \n \n    \n   \n         \n      \n \n  *Alcoholism; chronic heart, liver, or lung disease; chronic renal failure; cigarette smoking; \ncochlear implant; congenital or acquired asplenia; cerebrospinal fluid leak; diabetes mellitus; \ngeneralized malignancy; HIV; Hodgkin disease; immunodeficiency; iatrogenic \nimmunosuppression; leukemia, lymphoma, or multiple myeloma; nephrotic syndrome; solid organ transplant; sickle cell disease; or other hemoglobinopathies. \nFor PCV13 -experienced adults who completed the recommended vaccine series, the shared \nclinical decision-making recommendation regarding the use of a supplemental PCV20 or PCV21 \ndose remains unchanged. The current age threshold is maintained because, under previous \nrecommendations, PCV13-vaccinated adults were only considered to have received all \nrecommended vaccine doses after receiving one final dose of PPSV23 at or after age 65. The proposed language is as follows: \nShared clinical decision- making is recommended regarding use of a supplemental \nPCV20 or PCV21 dose for adults aged ≥65 years who have completed their recommended vaccine series with both PCV13 and PPSV23. \nFor PCV13 -experienced adults who have not completed the recommended vaccine series, the \nproposal is to remove the option to complete the vaccine series with PPSV23 and instead to recommend a single dose of either PCV20 or PCV21. \nThe proposed language is as follows: \nA single dose of either PCV20 or PCV21 is recommended as an option for adults aged \n≥19 years who have started their pneumococcal vaccine series with PCV13 but have not \nreceived all recommended pneumococcal vaccine doses. \nThe team will work to update guidance for populations experiencing serotype 4 disease. \nVote: Pneumococcal Vaccines \nThe vote occurred later in the day following public comment but is incorporated here for \ncontinuity. \nDr. Keipp Talbot (ACIP Chair ) read the following proposed ACIP voting language for \npneumococcal vaccines into the record: \nACIP recommends a pneumococcal conjugate vaccine (PCV) for all PCV -naïve adults \naged ≥50 years \nMotion/Vote: Pneumococcal Vaccines \nD\nr. Loehr motioned to approve the proposed v ote recommendation for pneumococcal vaccines, \nstating, “ ACIP recommends a pneumococcal conjugate vaccine (PCV) for all PCV -naïve adults \naged ≥50 years.” Dr. Cineas seconded the motion. No COIs were declared. The motion carried \nwith 14 favoring and 1 opposing. The disposition of the vote was as follows: \n1\n4 Favored: Brooks, Brewer, Maldonado, Kamboj, Cineas, Asturias, Schechter, Jamieson, \nC\nhu, Moser, Shaw, Chen, Kuchel, Talbot \n1 Opposed: Loehr \n0 A\nbstained: \n13 \n \n   \n \n \n   \n   \n \n  \n \n \n \n \n    \n \n   \n \n  \n \n \n  \n  \n \n  \n  \n   \n \n \n \n    \n  \n \n   \n \n \n \n   \n \n    \n   \n \n \n \n  INFLUENZA VACCINE S \nDr. Jamie Loehr, Chair of the ACIP Influenza Vaccine Work Group, opened the influenza session by announcing that FluMist\n® (Live Attenuated Influenza Vaccine) was approved by the \nFDA for self-administration or administration by a caregiver on September 20, 2024. This \nchange is expected to take effect for the 2025-26 influenza season. Currently, FluMist can only be given by a healthcare provider but in the future it will be available for shipment to private homes. \nDr. Sascha Ellington (CDC/NCIRD) presented an update on the 2023-24 end-of-season \ninfluenza vaccine effectiveness. This season was a predominant A(H1N1)pdm09 season with \nlower levels of A(H3N2) and B/Victorian circulation. Peak activity occurred in week 52 of 2023. \nVaccines were quadrivalent and included A(H1N1)pdm09, A(H3N2), and B components. \nThe four CDC VE investigating networks are the Investigating Respiratory Viruses in the Acutely \nIll (IVY), the New Vaccine Surveillance Network (NVSN), the US Flu Vaccine Effectiveness Network (US Flu VE), and the Virtual SARS-CoV-2, Influenza, and Other Respiratory Viruses Network (VISION). The networks include all ages across inpatient and outpatient settings and are geographically diverse, including patients from 23 states. \nDr. Ellington described the methods for estimation of influenza vaccine effectiveness for the \n2023-2024 season. Enrollees were people with acute respiratory illness who presented for \nmedical care. The test- negative design was used to determine VE. Vaccination odds were \ncompared among case patients with influenza confirmed by molecular assay versus control patients testing negative for influenza and SARS -CoV -2. Persons were classified as vaccinated \nbased on receipt of any 2023– 24 seasonal flu vaccine according to medical records, \nimmunization registries, claims data, and/or self-report. VE was calculated as 1 minus the \nadjusted odds ratio times 100%.  Estimates were adjusted for geographic region, age, and calendar time of illness. In IVY, US Flu VE, and VISION estimates were also adjusted for sex and race and ethnicity, and the US Flu VE estimates were also adjusted for days between \nillness onset and enrollment and self- reported general health status. \nThe final estimates for VE among children 6 months to 17 years of age against any influenza \nranged from 56% to 59% in outpatient settings and 59% to 64% in the inpatient setting. These \nwere comparable to the interim estimates that included data through the end of January that were presented at the February 2024 ACIP meeting. The final estimate for VE against influenza \nA in the pediatric population ranged from 43% to 50% in outpatient settings and 44% to 51% in the inpatient setting, similar to the interim estimates. The final estimate for VE against influenza B in the pediatric populati on ranged from 64% to 74% in outpatient settings and 78% to 85% in \ninpatient settings; the interim estimates were similar in the outpatient setting but data were insufficient for an interim estimate for children in the inpatient setting. \nFor adults aged 18- to 49 years of age, the final estimate for influenza VE against any influenza \nranged from 37% to 54% in outpatient settings and 51% to 53% in inpatient setting s. The final \nestimate in this age group for VE against influenza A ranged from 20% to 45% in outpatient \nsettings and 37% to 44% in inpatient settings and for influenza B, 67% to 75% in outpatient \nsettings and 68% to 72% in inpatient settings. \n14 \n \n      \n   \n   \n \n \n \n    \n \n  \n  \n   \n \n \n \n  \n  \n \n  \n  \n  \n \n \n \n    \n   \n \n \n \n \n \n \n \n \n  \n \n  \n  \n \n \n \n  \n  \n \n  For adults aged 50- to 64 years of age, the final estimate for influenza VE against any influenza \nranged from 22% to 44% in outpatient settings and 40% to 48% in inpatient setting s. The final \nestimate in this age group for VE against any influenza A ranged from 11% to 39% in outpatient settings and 38% to 39% in inpatient settings and for influenza B, 81% to 82% in outpatient \nsettings and 61% to 86% in inpatient settings. \nFor adults ≥65 years of age, the final estimate for influenza VE against any influenza ranged \nfrom 37% to 40% in outpatient settings and 31% to 36% in inpatient settings . The final estimate \nin this age group for VE against any influenza A ranged from 36% to 37% in outpatient settings \nand 27% to 35% in inpatient setting s and for influenza B, 67% to 80% in outpatient settings and \n39% to 66% in inpatient settings. The three active surveillance networks were used to estimate the VE against subtypes of \ninfluenza A. For A(H1N1), all estimates were under 50% for adults, with the lowest VE observed \nin adults <65 years of age. VE was about 50% from NVSN in inpatient and outpatient settings \nfor children. The US Flu network estimated 60% VE for children in outpatient settings. \nBecause it was a predominantly an A(H1N1) season, less data were available for A(H3N2), \nresulting in wider confidence intervals. The lowest VE was among adults ≥65 years old. For \nchildren, VE was around 40% against hospitalization and 50% against outpatient influenza from \nNVSN. The US Flu network estimated lower VE for children in outpatient settings. \nDr. Ellington concluded that vaccination with a 2023– 2024 influenza vaccine reduced the risk of \nmedically attended influenza outpatient visits and hospitalizations among children, adolescents, \nadults, and adults over age 65 years. Most results were consistent across all four networks and \nthese end-of -season estimates were similar to interim estimates from February. \nDr. Tom Shimabukuro (CDC/NCIRD) provided an update on Highly Pathogenic Avian Influenza \nA (H5N1). A substantial number of cases in 2024 were reported in the U.S. and are attributed to \noutbreaks in dairy cattle. Historically, human infection has resulted from exposure to sick or \ndead poultry and live poultry markets, as well as to other infected animals; in the case of the U.S. outbreak, these animals were dairy cows. Limited, non-sustained human-to-human transmission has occurred globally in the past but has not been seen in the U.S. \nCDC prioriti es include supporting and engaging public health and agricultural partners, \nprotecting human health and safety, understanding the risk to people from HPAI A(H5N1) \nviruses, and assessing HPAI A(H5N1) viruses for genetic changes. \nAs of October 18, 2024, USDA has confirmed HPAI A(H5N1) in U.S. dairy herds in 324 farms \nacross 14 states. A significant decrease in the quality and production of milk was observed in \nearly 2024. USDA reported HPAI A(H5N1) confirmed cases in cows from Texas and Kansas on \nMarch 25, 2024. \nIn 2024, there were 27 reported human cases in the U.S., most of whom had known exposure \nto dairy cattle or poultry. Additionally, one case in Missouri had an unknown exposure. The \nindividuals exposed to dairy cattle and poultry experienced mild clinical symptoms, such as mild \neye irritation, respiratory issues, and systemic effects. \n15 \n \n  \n \n  \n \n    \n  \n \n  \n \n  \n \n \n \n  \n  \n \n \n \n \n \n    \n \n \n   \n \n  \n  \n  \n    \n \n  \n \n \n  \n  \n \n \n  The Missouri case, which had multiple underlying health conditions, was hospitalized with gastrointestinal symptoms, chest pain, and other symptoms not typical of respiratory illness. The \nillness, however, was not severe, and the patient recovered. The case was discovered through \nregular surveillance. The case’s contacts’ serology results are pending. \nSequences maintain primarily avian genetic characteristics and lack changes to make the virus \nbetter adapted to infect or spread among humans. There is no impact on the current CDC influenza diagnostic assay’s ability to detect A(H5N1) viruses and no known markers of \nresistance were detected. Hemagglutinins of human influenza viruses remain antigenically \nrelated to two available Candidate Vaccine Viruses (CVVs). Assessment of newer California viruses is underway. Dr. Shimabukuro reiterated that seasonal vaccines are not expected to protect against influenza A(H5N1) viruses. \nAll people with direct or close exposure to animals infected with influenza A(H5N1) should be \nmonitored for illness during exposure and 10 days after their last exposure. Signs and \nsymptoms may include fever, cough, sore throat, runny or stuffy nose, muscle or body aches, \nheadaches, fatigue, eye redness, shortness of breath, or difficulty breathing and l ess commonly, \ndiarrhea, nausea, vomiting, or seizures. If signs or symptoms develop, these persons should \nseek medical evaluation for possible influenza testing and antiviral treatment. Symptomatic \npeople should be isolated away from others during this evaluation. State and local health \ndepartments can facilitate testing and treatment. \nThe CDC supports state and local health departments monitoring exposed people during and \nfor 10 days after the last exposure. Over 5,100 people have been monitored, and over 260 have \nbeen tested due to targeted surveillance, and 26 cases have been detected. Through enhanced \nregular surveillance, 54,360 specimens have been tested, with one person testing positive (the \nMissouri case). There have been no indicators of unusual influenza activity in people, including avian influenza A(H5N1), in regular surveillance. \nIn June 2024, the Michigan Department of Health collected blood samples from 35 dairy \nworkers. The samples were tested for antibodies against influenza A(H5N1) and a seasonal influenza virus. None of the participants showed neutralizing antibodies specific to the avian \ninfluenza A(H5N1) virus although many showed antibodies to seasonal influenza viruses . This \nsuggests that these people were not previously infected with influenza A (H5N1) despite the high risk of exposure. \nFerrets are used to study both the severity and transmissibility of influenza. They exhibit many clinical signs of infection similar to those observed in humans. Dr. Shimabukuro shared that in a study of A(H5N1) viruses, ferrets were inoculated with two A(H5N1) virus strains: Michigan and \nTexas. The results showed that the Michigan virus caused less severe illness in ferrets than the \nTexas virus. The Michigan virus resulted in less weight loss and lower mortality rates. However, \ntransmission through respiratory droplets was similarly observed for both viruses. The Michigan \nvirus is considered better to represent the currently circulating strains of the virus. \n16 \n \n   \n \n  \n \n \n  \n \n \n  \n  \n \n  \n  \n \n  \n \n \n  \n  \n \n \n   \n \n \n   \n \n \n  \n \n \n \n  \n \n \n \n   \n   \n \n \n \n  The CDC Influenza Risk Assessment Tool (IRAT) is an evaluation tool for prioritizing resources for pandemic preparedness. The U.S. government subject matter experts assess viruses based \non ten risk factors related to their emergence and public health impact. Emergence is the risk of \na novel influenza virus acquiring the ability to spread quickly and efficiently in people. The public health impact is the potential severity of human disease caused by the virus and the burden on society. The IRAT is not intended to predict a pandemic and is not to be used to assess the overall population or individual risk. Based on available data, CDC’s current assessment is that the risk to the general public from avian influenza A(H5N1) virus remains low. \nIn summary, the overall risk to the public for HPAI A(H5N1) remains low. There is a greater risk for people with close, prolonged, or unprotected exposure to infected animals or environments contaminated by infected animals. Exposed individuals should monitored for symptoms after the first exposure and for 10 days after the last exposure. \nDr. Chu asked whether CDC had sequencing data to indicate changes in receptor binding with \nthe Texas and Michigan strains that were used in the ferret studies. \nDr. Shimabukuro responded that he currently does not have the data available. However, he \nstated that the sequences primarily retain avian genetic characteristics and do not exhibit \nchanges that would enhance the virus’s adaptation to infect humans. \nDr. Chu inquired whether there can be speculation about why the two viral strains' lethality is \ndifferent and whether any household studies are being done to examine transmission in the farm worker communities. \nDr. Shimabukuro said he would have to contact the lab for additional information. He stated that \nCDC has teams in the field working with partners to do epidemiologic investigations, contact \ntracing, and studying animal -to-human and human-to-human spread, so there will be m ore \ninformation to come.  \nDr. Schechter asked if there is additional seroprevalence data for poultry workers in recent \nyears. He also sought comments on the genetic differences between the Michigan and Texas strains. \nDr. Shimabukuro said he thought that there might be data from outside the U.S. but was unsure \nof any data within the U.S. He agreed to follow up on the differences between the strains. Dr. Shaw inquired if H5N1 has been found in wastewater and whether it is possible to identify \nhumans from animal sources. He also asked if there has been specific outreach to dairy and poultry farm workers to encourage them to receive seasonal influenza vaccines. \nDr. Shimabukuro stated that wastewater surveillance is being done in addition to regular \nsurveillance. H5N1 has been detected in wastewater and has been usually in areas associated \nwith animals or animal products but it’s difficult to definitively determine source as animal or \nhuman. There is a program to support jurisdictions with infected herds, promoting seasonal \nvaccinations for agricultural workers to protect them from seasonal influenza and potentially \nhelp prevent respiratory illnesses. \n17 \n \n  \n \n \n  \n   \n    \n \n    \n \n  \n \n \n \n   \n \n   \n \n \n  \n \n  \n \n \n \n \n  \n \n \n \n \n  \n \n \n   \n \n \n \n  \n \n \n  Dr. Loehr inquired whether a patient who receives the flu vaccine and contracts the flu will \nexperience a less severe case. \nDr. Ellington clarified that none of the VE studies presented today were designed to answer this \nquestion, but there are studies with other designs that show less severe illnesses with \nvaccination. Dr. Grohskopf added that there are other studies that suggest this. \nDr. Chris Hahn addressed an earlier question about wastewater as an epidemiologist serving \nstates affected by H5N1.  Although wastewater detection is taking place, it remains unclear where the contamination originates. All impacted states have implemented targeted v accination \nefforts, and we are careful in our messaging to clarify that these vaccinations are intended to protect against seasonal influenza . \nDr. Shimabukuro clarified a previous answer on the ferret studies discussed. While he does not \nhave genetic sequencing, he would like to reinforce that the Michigan human virus better represents currently circulating viruses. \nDr. Kamboj asked whether challenge studies with the candidate virus vaccines are being done \nin ferrets . \nDr. Shimabukuro confirmed that other ferret studies are being conducted. \nDr. Chu asked if the at-home flu test detects H5 and whether there is a plan to scale these types of tests in farmworker communities if they do. \nDr. Shimabukuro clarified that if an over -the-counter test detects influenza A, it should also be \nable to detect influenza A(H5N1 ). However, these tests do not do subtyping, which must be \ndone by a laboratory and then confirmed at CDC. There are partnering programs to explore \nexpanding testing capacity if needed; that work is ongoing.  Dr. Maldonado recalled that the transmission from cows to cats involved drinking raw milk. She \ninquired about additional messaging around this information, such as data on the pasteurization \nof milk. \nDr. Shimabukuro shared that the CDC recommends that people do not drink raw milk. All the \ndata point to pasteurization resulting in a safe commercial milk supply. Dr. Daskalakis reinforced that pasteurization is highly effective in addressing H5N1. Both CDC \nand FDA have issued clear guidance on raw milk.  \nDr. Jeanne Santoli (CDC/NCIRD) shared the Vaccine for Children (VCF) resolution update. The \npurpose of this resolution is to (1) update the Inactivated Influenza Vaccine component of the \nresolution to add options for vaccination of 18-year -olds who are solid organ transplant \nrecipients and (2) update the links in the contraindications and precautions sections of both \ncomponents of the resolution. \n18 \n \n   \n \n  \n \n \n \n \n \n  \n   \n \n   \n    \n \n \n \n \n \n  \n \n \n \n \n  \n \n \n \n  \n \n      \n  \n \n  \n  There were no changes to the inactivated component of the influenza vaccine-eligible groups \nand the recommended vaccine schedule and dosage intervals. Two vaccine products (Fluzone® \nHigh-Dose and FLUAD®) have been added, which are indicated for people ≥65 years and older. \nA table note was added that states, “Persons aged 18 y should receive an age-appropriate influenza vaccine (i.e., one approved for their age), with the exception that solid organ transplant recipients on immunosuppressive medication regimens may receive high-dose inactivated influenza vaccine (HD -IIV3) or adjuvanted inactivated influenza vaccine (aIIV3) as \nacceptable options, without a preference over age-appropriate IIV3s.” No changes to dosage, \ncontraindications, or precautions were made. There is, however, an update to the link for this \ninformation. \nNo changes have been made to the live attenuated influenza vaccine-eligible groups or their \nrecommended vaccine schedule and dosage intervals. There are recommendations for the \ndosage to be consistent with how it is depicted in the resolution of the inactive influenza vaccine \ncomponent and an update to the link of the contraindications and precautions information. \nDr. Kamboj requested that the Work Group consider a high-dose flu vaccine beyond solid organ \ntransplant, especially for hematopoietic stem cell transplant recipients. \nDr. Brooks questioned whether there was any consideration for younger children. \nDr. Wharton clarified that this resolution aligned VFC with the committee's vote in June. \nYounger children were not considered. \nDr. Loehr inquired whether there was a recommendation for recombinant RIV in 18-year -olds \nand, if not, why it was not considered. \nDr. Santoli confirmed that this vaccine was not included in the VFC program because it was not \nbrought forward for inclusion when it was licensed. Managing a vaccine designated to only one \nage cohort is also challenging. \nDr. Loehr motioned to approve VFC resolution for vaccines to prevent influenza. Dr. Cineas seconded the motion. \nVote: Influenza Vaccines \nDr. Keipp Talbot (ACIP Chair ) read the following proposed ACIP resolution for Influenza \nVaccines for Children (VFC) into the record: \nApprove the Vaccines for Children (VFC) resolution for vaccines to prevent influenza. \n19 \n \n  \n    \n \n   \n    \n \n \n     \n \n        \n      \n \n  \n \n    \n   \n  \n \n \n \n  \n  \n   \n \n \n \n  \n  \n  \n \n  \n  \n \n \n \n \n   Motion/Vote: Influenza Vaccines \nDr. Loehr made a motion to approve the VFC resolution for influenza vaccines. Dr. Cineas \nseconded the motion. No COIs were declared. The motion carried with 15 favoring and 0 \nopposing. The disposition of the vote was as follows: \n15 Favored: Asturias, Brewer, Brooks , Chen, Chu, Cineas, Jamieson, Kamboj, Kuchel, \nLoehr, Maldonado, Moser, Schecter, Shaw and Talbot \n0 Opposed:\n0 Abstained: \nCHIKUNGUNYA VACCINE S \nDr. Edwin Asturias, chair of the ACIP Chikungunya Vaccines Work Group, introduced the \nsession. The Work Group was formed in May 2022. The currently available vaccine, Valneva’s \nlive attenuated vaccine, was licensed in November 2023. A virus -like particle vaccine has been \nsubmitted for licensure by Bavarian Nordic. The Work Group is developing policy options for \nACIP’s consideration for using the chikungunya vaccine among U.S. persons at risk of chikungunya, including travelers, laboratory workers, and residents of U.S. territories and states \nwith risk of transmission. \nDr. Susan Hills (CDC/NCEZID) updated the committee on chikungunya and chikungunya \nvaccines. Chikungunya is a mosquito-borne disease. Key vectors are Aedes aegypti and Aedes \nalbopictus mosquitoes. It is typically transmitted in tropical and subtropical regions, with about \n120 countries and territories where transmission has ever been documented. A key feature of \nthe virus is that it periodically causes explosive outbreaks, often with high attack rates. \nClinical illness is characterized by fever and joint pain, which is typically severe and can be \ndebilitating. The approach to management is supportive; no specific antiviral treatment is \navailable. Rare serious complications include myocarditis, hepatitis, and neurologic illness. Deaths are rare and are primarily seen in older adults, particularly those with comorbidities and \nyoung infants. Acute symptoms usually resolve in 7-10 days. Some patients have continuation \nor relapse of their joint symptoms. Studies have reported variable proportions of patients with \npersistent symptoms, but ongoing arthralgia of variable severity might be present in up to about half of patients at 3 months after infection and up to about 30% at 12 months. It is a reportable \ndisease in the United States; approximately 100-200 cases are reported annually among U.S. \ntravelers, although there is likely substantial underdiagnosis and underreporting. Infections are \nmost commonly acquired in Asia and the Americas, with specific locations of acquisition \ninfluenced by local transmission patterns, which vary from year to year. Unquestionably, the greatest risk for US travelers to acquire chikungunya is traveling to an area with an outbreak. \nDr. Hills reminded the committee that there is currently one licensed vaccine in the U.S. and one \nvaccine submitted to the FDA for licensure. The licensed vaccine is a live attenuated vaccine \nmanufactured by Valneva as IXCHIQ\n®. It was licensed in November 2023 and is currently \napproved for use in adults aged 18 years and older. This vaccine has a single-dose schedule. \n20 \n \n  \n \n  \n  \n \n \n \n \n \n  \n \n  \n  \n \n  \n \n \n \n \n \n \n \n \n \n \n \n \n   \n  \n \n  \n \n \n \n  \n \n \n ACIP approved recommendations for use of this vaccine in adult travelers in February 2024. \nThe recommendations note that ACIP recommends the live attenuated chikungunya vaccine for \npersons aged ≥18 years traveling to a country or territory where there is a chikungunya \noutbreak. In addition, the vaccine may be considered for certain persons traveling to a country \nor territory without an outbreak but with evidence of chikungunya virus transmission among humans within the last 5 years. The groups include persons aged >65 years, particularly those with underlying medical conditions, who are likely to have at least moderate exposure to mosquitoes, or persons staying for a cumulative period of 6 months or more. ACIP also \nrecommends live attenuated chikungunya vaccine for laboratory workers who are potentially \nexposed to the chikungunya virus. Updates on this vaccine include that for adolescents aged \n12-17 years, Valneva plans a submission to the FDA this year, which, if ultimately approved, will allow use in this age group. A clinical trial began in December 2023 and is in progress for children aged 1-11 years. Finally, monitoring of the vaccinated cohort from the pivotal clinical \ntrial in adults aged ≥18 years is continuing to investigate the persistence of seroresponse \nfollowing the single dose of the vaccine. At two years, a high seroresponse rate of 97% was \nmaintained. Monitoring will continue for 10 years to determine if a booster dose will be needed in the future. \nBavarian Nordic manufactures the second vaccine, and licensure is possible in February 2025. \nThe virus -like particle vaccine's intended age group is adolescents and adults aged ≥12 years. \nThe vaccine has a single-dose primary schedule. Like the live attenuated vaccine, the virus -like \nparticle vaccine will be licensed through the accelerated approval pathway. Traditional approval \nwould have been challenging, and clinical development would likely have been delayed if this approach had been required. FDA can grant accelerated approval for products that are for \nserious conditions and that fill an unmet medical need. In this pathway, the demonstration of \neffectiveness is based on controlled clinical trials showing the vaccine affects a surrogate endpoint that is reasonably likely to predict clinical benefit. For the virus -like particle vaccine, the \nmarker of protection was based on a neutralizing antibody titer estimated from a validated non-human primate model. This pathway has a post-licensure requirement for controlled trials to \nconfirm clinical benefit. \nThe ACIP Chikungunya Vaccines Work Group has four groups for whom vaccine \nrecommendations are being considered. These include travelers, laboratory workers, residents of U.S. territories at risk of chikungunya virus transmission, and residents of U.S. states at risk of transmission. For the live attenuated chikungunya vaccine, ACIP has made \nrecommendations for use among travelers aged 18 years and older and among laboratory workers; the Work Group is currently considering policy options to present to ACIP for use of the vaccine among residents of US territories and states with risk of transmission. Regarding the virus-like particle chikungunya vaccine, policy options for the use of the vaccine among all four groups are under consideration and will be presented for ACIP’s consideration at future \nmeetings.  \nDr. Victoria Jenkins (Bavarian Nordic) discussed the virus -like particle chikungunya vaccine \n(CHIKV VLP). CHIKV VLP consists of 3 recombinant proteins that mimic the virus but cannot \nreplicate in the host. It is adjuvanted with aluminum hydroxide in a single 40µg VLP dose administered intramuscularly. The PDUFA target action date is February 14, 2025. The \nproposed indication is to prevent CHIKV infection in individuals ≥ 12 years of age. The proposed \ncontraindications are hypersensitivity , including severe allergic reactions, to any component of \nthe vaccine. \n21 \n \n   \n   \n \n \n  \n   \n  \n \n \n   \n \n \n \n \n \n   \n \n \n \n  \n \n \n \n  \n \n \n \n \n \n  \n   \n  \n \n \n \n \n \n \n \n \n \n \n  A defined threshold of serum -neutralizing antibodies was used as a surrogate efficacy endpoint \nin Phase 3 clinical trials. The CHIKV luciferase assay used in the study was based on the \nCHIK181/25 live-attenuated virus (Asian lineage) engineered to express luciferase transgene. \nThe neutralization assay was based on an 80% reduction of luciferase activity, resulting in an NT\n80 value. The assay measures cross -neutralization as the vaccine is heterologous to the \nassay strain (West African vs. Asian). \nThe submitted vaccine clinical program included three Phase 2 studies and two Phase 3 studies \nconducted in the U.S. The Phase 2 dose and schedule studies were conducted in healthy \nparticipants aged 18-45 years. The single 40 µg CHIKV VLP adjuvanted dose was chosen for \nfurther development because it had superior immunogenicity after the first vaccination, showed a rapid and durable response, and was well -tolerated. The study also looked at the need for a \nbooster dose, but the need for a booster is still unknown. \nThe Phase 3 studies were completed in parallel, placebo-controlled, and conducted in the U .S. \nOne was done in participants 12 to 64 years of age and the other in adults ≥65 years of age. \nBoth studies had coprimary end points of superiority of GMT at day 22 vs. the placebo, difference in the seroresponse rate vs. placebo at day 22, and safety. In addition, in the study of \nadolescents and adults, lot-to-lot consistency of anti -CHIKV SNA GMT at Day 22 was evaluated \nin a subgroup of participants 18-45 years of age. The demographic profile of participants in both \nstudies were balanced between vaccine and placebo groups. All co-primary and secondary endpoints were met in both studies. CHIKV VLP vaccine was well -tolerated in individuals 12 to \n64 years of age. The incidence of adverse events of special interest ( AESI) and medically -\nattended adverse events ( MAAE) did not differ between the CHIKV VLP vaccine group and the \nplacebo group in individuals 12 to 64 years. CHIKV VLP vaccine was well -tolerated in \nindividuals ≥ 65 years of age. Incidence of AESI and MAAE did not differ between the CHIKV \nVLP vaccine group and the placebo group in individuals ≥65 years of age. \nDr. Jenkins summarized that the Phase 3 trials demonstrated a rapid and robust immune \nresponse in individuals ≥12 years of age. A durable and boostable immune response was also \nobserved in a subpopulation of the Phase 2 trial. The vaccine was well tolerated, and there were no treatment-related SAEs, as determined by the sponsor. Most solicited and unsolicited adverse events were mild or moderate in intensity. \nDr. Cineas inquired whether the studies included immunocompromised patients and those with \nchronic medical conditions. \nDr. Jenkins responded that the Phase 3 study only included healthy participants. However, \npersons with stable immunocompromising conditions will not be excluded from a Phase 3B \nconfirmatory efficacy study . \nDr. Susan Hills (CDC/NCEZID) concluded with a review of the work group’s interpretation of \ndata for the virus -like particle chikungunya vaccine following their preliminary review of the data. \nRegarding VE, results are based on immunogenicity data since no VE data is available. Short-\nterm immunogenicity data reflecting seroresponse rates at 3 weeks after vaccination are available from 2,750 vaccinated subjects in two Phase 3 studies, most of whom were adults \naged 18-64 years, with smaller numbers of adolescents and older adults with data, with about \n200 subjects with data in each of these age groups.  The work g roup noted there was a robust \nresponse to vaccination, with seroresponse rates 21 days after vaccination of 98% in adolescents and younger adults and 87% in older adults, and seroresponse rates at 6 months after vaccination of 86% and 76% in the younger and older age groups respectively. \n22 \n \n  \n \n \n \n   \n \n  \n  \n      \n     \n \n \n   \n \n \n  \n      \n \n  \n \n \n    \n  \n \n  \n  \n  \n  \n \n \n \n \n \n  \n \n \n \n \n \n \n Data after 6 months are not yet available from Phase 3 studies, so the need for a booster dose \nis unknown. \nSafety data are available from about 3,000 vaccinated subjects in two Phase 3 studies, most of \nwhom were adults aged 18-64 years. Data from smaller numbers of adolescents aged 12-17 years and adults aged ≥65 years are also available, with about 210 subjects with data in each \nage group. Based on the overall data, t he work group concluded that the overall safety profile of \nthe vaccine was acceptable. Solicited adverse events were reported within 8 days of \nvaccination. The following data reflect results among adolescents and adults aged 12 -64 years. \nLocal events were reported by 24%, with 0.2% graded as severe. Solicited systemic events \nwere reported by 32%, with severe events in fewer than 2% of subjects. The most frequent events were fatigue, headache, and myalgia, all reported by 18 to 20% of vaccinated persons. There was no concerning signal with arthralgia after vaccination. One serious adverse event – a \nretinal detachment --was assessed as related by the study investigator but unrelated by \nthe safety monitoring committee chair. For adults ≥65 years , all adverse event rates were lower \nthan those seen in 12-64 -year-olds. \nThe work group summary for the c hikungunya VLP vaccine: \n• Will provide an option, in addition to the licensed live attenuated vaccine, for vaccination \nof adults aged ≥18 years \n• Will provide a new option for adolescents aged 12– 17 years \n• Immunogenic vaccine but no vaccine effectiveness data, which will be gathered post-\nlicensure, and the need for a booster dose is currently unknown \n• There are no apparent safety concerns, but safety data only from ~3,000 people, so data are insufficient to detect rare events, and post-marketing surveillance will be important \n• Work g roup to conduct comprehensive data review and present GRADE assessment as \npart of the Evidence to Recommendations framework at a future meeting \nDuring 2025, the work g roup anticipates presenting recommendations for ACIP’s consideration \nand asking for votes on vaccine recommendations in various groups, including the use of live \nattenuated vaccine among travelers aged 12-17 years, use of the virus- like particle vaccine in \ntravelers aged ≥12 years, use of the virus -like particle vaccine among laboratory workers, use of \nboth vaccines among residents of U.S. territories with transmission risk, and use of both vaccines among residents of U.S. states with transmission risk. \nDr. Schechter inquired about short- and long-term plans for using the VLP vaccine in pregnant \nindividuals. \nDr. Hills confirmed that the work group is discussing the topic and will be able to provide \nadditional details at a future ACIP meeting. The use of the live attenuated vaccine has previously been considered. One of the main recommendations is that pregnant women avoid \ntraveling to areas with CHIKV if possible, particularly during an outbreak, due to the concern of \ninfection and subsequent transmission during the intrapartum period. If travel is unavoidable, \nthe licensed vaccine should be considered a precaution for use, with avoidance during the first \ntrimester and after 36 weeks of gestation. \nDr. Chu asked whether there were any Development and Reproductive Toxicity (DART) studies \nfor the VLP vaccine candidate. \n23 \n \n  \n \n   \n \n \n \n  \n \n \n \n   \n \n \n  \n \n   \n \n   \n  \n \n  \n \n  \n   \n \n  \n \n \n \n \n   \n \n  \n \n    \n     \n \n \n Dr. Hills clarified that she was referring to animal data and redirected the question to Dr. \nJenkins. \nDr. Jenkins confirmed that DART data are available and referred to a colleague, Dr Vang. \nDr Vang confirmed that DART studies were conducted in rabbits and rats. The results showed \nthat the vaccine was safe and there were no observations of concern. \nDr. Maldonado questioned whether the work group was considering making preferential recommendations or whether there might be blanket recommendations for both vaccines and asked whether the work group would continue to monitor strains circulating in the Western Hemisphere. \nDr. Hills confirmed that the vaccines would be considered independently due to the differences \nbetween the vaccines and the way immunogenicity and safety were assessed. For example, with immunogenicity, a different assay was used with a different marker for protection for each vaccine, so those comparisons are difficult. For safety, data are only available for about 4,000 subjects for each vaccine , and with such little data, it’s hard to make definitive comparisons. The \ndata suggest that the vaccines will protect against the various chikungunya strains, but as usage increases, CDC will be looking for any evidence of vaccine failure. \nDr. Asturias reiterated that the work group should consider the vaccines independently because the surrogates of protection differ. However, given the increasing burden in the Americas, having the option of two vaccines is encouraging. \nCOVID -19 VACCINES \nDr. Robert Schechter (ACIP, Work Group Chair) introduced this session on behalf of the ACIP \nCOVID -19 Vaccines Work Group. As a reminder, ACIP recommended 2024– 2025 COVID-19 \nvaccines as authorized or approved by the FDA in persons ≥6 months. Everyone ≥5 years \nshould get one dose of a 2024– 2025 v accine. Children aged 6 months -4 years need multiple \ndoses of COVID -19 vaccine to be up to date, including at least one dose of the 2024– 2025 \nvaccine. Moderate or severely immunocompromised people may receive additional 2024– 2025 \nvaccine doses. There are no recommendations for additional 2024– 2025 doses for older adults. \nToday’s session will focus on additional doses for adults ages 65 years and older and moderate \nor severely immunocompromised people. \nDr. Georgina Peacock (CDC/NCIRD) presented the implementation considerations for \nadditional COVID -19 vaccine doses. For children, coverage of 2024– 2025 vaccine to date is \n3.7% vs. 3.1% of 2023– 2024 vaccine at this time last year. For adults ≥18 years of age, \ncoverage of 2024– 2025 vaccine is 11.7% vs. 6.8% 2023– 2024 vaccine at this time last year, \nand for ages ≥75 years , coverage is 30.6% vs. 17.7% last year.  \nAmong adults ≥65 years of age, vaccination coverage for ≥1 2023– 2024 COVID-19 vaccine \ndose through June 2024 was about 40% and 8.9% for ≥2 doses of 2023– 2024 COVID-19 \nvaccine, based on the National Immunization Survey-Adult COVID Module. Within the group \nreceiving ≥2 doses, higher coverage is seen in urban than in rural areas. Minimal differences in \n≥2 dose coverage are seen by low, moderate, or high Social Vulnerability Index. Higher \ncoverage is seen in people with underlying health conditions and those with a healthcare \nprovider’s recommendation. \n24 \n \n  \n \n \n \n  \n \n \n \n \n \n  \n \n \n    \n \n   \n  \n \n   \n   \n    \n \n  \n  \n \n  \n \n  \n  \n  \n \n \n   \n \n   \n \n \n \n   \n   \n  \n 36.8% of ≥65-year -olds surveyed from April -June 2024 had received ≥1 2023– 2024 COVID-19 \nvaccine dose. Of that 36.8% who received ≥1 dose, 20% were vaccinated with ≥2 doses, 44.3% \n“definitely will get another dose,” 30.9% “probably will get another dose,” and 4.7% “probably or \ndefinitely will not get another dose.” There was greater intention to get a second dose in people ≥80 years of age and people living in urban areas. From April to June 2024, there was a modest increase in the intent of adults ≥65 years of age to receive another dose. \nAmong immunocompromised adults aged ≥18 years, 5.4% received ≥2 doses of 2023– 2024 \nCOVID -19 vaccine through June 2024. Within this group, higher coverage is seen among \nimmunocompromised adults ≥65 years old, those living in suburban areas, those who had \nreceived a healthcare provider recommendation, and those with insurance.  \nThe Omnibus Survey of adults ≥18 years of age with health conditions and adults age d ≥65 \nyears , conducted in August 2024, asked respondents whether they intended to receive a \nsecond dose for the current season if it were recommended. Overall, one -third of those \nsurveyed intended to receive a second dose. Intentions were higher among adults over 65 \nyears old. There was lower intent in rural areas and among those who are uninsured. \nThe proposed recommendations for additional doses would not be overly burdensome to \nimplement because the additional dose would be the same formula as the current vaccine, there \nis administration infrastructure and product can be used, and the recommendations can be \nintegrated into existing systems and structures. Minor challenges include the need for additional \neducation and a possible increase in existing vaccine fatigue as well as availability at practices \nafter the fall supply has been exhausted.  The new proposed recommendations include “should” rather than “may” (or shared clinical \ndecision-making) recommendations for overall ease of implementation. The recommended and minimal interval for vaccination is consistent with language for other vaccines. It is also standardized across adults aged ≥65 years and immunocompromised populations, which eases \nimplementation. Furthermore, a minimum interval of 2 months allows for flexibility in vaccine administration when accounting for individual risks and circ umstances. \nOf adults aged ≥18 years who have received a 2024– 2025 COVID -19 vaccine, the majority \n(81.9%) received their vaccination at a pharmacy or drug store. Similarly, of adults aged ≥65 \nyears who received a 2024– 2025 COVID -19 vaccine, the majority (82.8%) have received their \nvaccination at a pharmacy or a drug store. Within pharmacy settings, “may” (or shared clinical decision-making) recommendations can be challenging. CDC has dedicated healthcare provider engagement to assist with the denial of vaccination that may take place due to changes in guidance. Differences in vaccine access can create disparities in uptake, and these may be \nexacerbated by due to issues with insurance, disability, and vaccination settings (e.g., long-term \ncare). \nDr. Swamy made a statement representing the American College of Obstetricians and \nGynecologists. The group is supportive of the COVID -19 vaccine in pregnancy . Data show that \nthe vaccine is safe and efficacious and decreases the risk of severe disease and hospitalization rates in infants when administered in pregnancy. Maternal vaccination can help reduce the risk \nof transmission to newborns during pregnancy, delivery, and breastfeeding. Due to the decreased rate of vaccination within this population, the group feels COVID -19 vaccine should \nbe prioritized and recommended. \n25 \n \n  \n  \n    \n \n    \n    \n \n      \n  \n \n   \n \n \n \n   \n \n \n \n \n \n \n  \n  \n  \n \n \n    \n  \n  \n \n  \n  \n \n \n   \n \n  \n   \n  \n \n Dr. Christopher Taylor (CDC/NCIRD) presented updates on COVID -19-associated \nhospitalizations. COVID -NET data captures 10% of the U.S. population, and data presented \ntoday will be limited to hospitalizations identified in 90 counties across 12 states. Hospi tals \nreported all positive SARS -CoV -2 test results within 14 days before or during \nhospitalizations. Clinical data are collec ted from an age- and site-stratified random sample. \nAdults ≥65 comprise 70% of all COVID –19–associated hospitalizations among adults ≥18 years \nof age from October 2023 to September 2024. Rates of COVID -19 hospitalizations are highest \namong adults ≥75 years of age. COVID –19–associated hospitalizations increased with age from \nOctober 2023 to September 2024. Rates among those ≥75 years of age are three times as high \nas adults aged 65-74 years , nearly nine times as high as adults aged 50- 64 years , and 24 times \nas high as adults 18-49 years of age . \nSince March 2020, rates of COVID –19–associated hospitalizations among adults aged ≥65 \nyears have decreased, but hospitalizations among adults aged ≥75 years remain the highest \nacross all age groups. Most adults aged ≥65 years hospitalized with COVID -19 have underlying \nmedical conditions. Adults aged ≥65 years remain at risk for severe outcomes during COVID – \n19–associated hospitalization. Between October 2023 and May 2024, 80% of all adults \nhospitalized with COVID- 19 who died in-hospital were aged ≥65 years. Data suggests that \ndeaths following hospital discharge are more common among older adults within 30 days of \nrelease. Fewer than half of adults aged ≥65 years hospitalized with COVID -19 have received \nany COVID -19 vaccine since September 2022. \nSome conditions defined as immunocompromising according to COVID -NET are time-bound \nrelative to admission for COVID -19-associated hospitalization. Immunosuppressive therapy is \nonly considered if treatment was received 12 months before admission. Cancer is only \nconsidered if treatment or diagnosis occurred in the 12 months before admission. Inhaled, \nintranasal, intramuscular, or intraarticular steroids are also not included. Between July 2023 and \nMay 2024, about 15.6% of people hospitalized with COVID -19 had an immunocompromising \ncondition. Three percent of children aged ≤4 years and 15-22% of hospitalized adults had an \nimmunocompromising condition. \nThe most common immunocompromising conditions were immunosuppressive therapy (46%), \nsolid organ malignancy (34%), steroid therapy (26%), and metastatic cancer (22%) . Few \npersons with an immunocompromising condition hospitalized with COVID -19 had received any \nCOVID -19 vaccine since September 2022. \nThe time since receipt of the most recent COVID -19 vaccine varied little by the status of the \nimmunocompromising condition. The risk for severe outcomes during COVID –19–associated \nhospitalization among children and adolescents varied little by immunocompromising condition \nstatus ; in contrast, the risk for severe outcomes during COVID –19–associated hospitalization \namong adults did vary by immunocompromising condition status. \nDr. Ruth Link -Gelles (CDC/NCIRD) presented the effectiveness of COVID -19 vaccines to inform \nACIP deliberations for two questions: the need for additional doses among those with \nimmunocompromise and the need for additional doses in those aged ≥65 years. Critical issues \nin COVID -19 vaccine effectiveness (VE) include the impact of time since dose on protection, the \nimpact of changing SARS-CoV -2 variants over time and variant/vaccine mismatch, and the \neffect of surges in disease, seroprevalence, and time since the last SARS -CoV -2 infection. As \ncontext for interpretation of VE, there were high rates of SARS-CoV -2 infection-induced \nimmunity by July -August 2023 among all age groups. \n26 \n \n   \n  \n \n \n       \n \n \n \n \n  \n \n    \n   \n   \n   \n \n   \n \n \n \n \n \n \n  \n \n \n \n \n \n \n \n  \n    \n   \n \n     \n \n \n  VE findings should, therefore, be interpreted as the added benefit of COVID -19 vaccination in a \npopulation with a high prevalence of vaccine- and infection-induced immunity. \nAbsolute VE is a measure comparing the frequency of health outcomes in vaccinated vs. unvaccinated people. Relative VE compares the frequency of health outcomes in people who received one type of vaccine to people who received a different type. For 2023-2024 COVID -19 \nVE, VE was measured by comparing people who received a 2023-2024 dose to those who did not, regardless of past vaccination. This is similar to how influenza VE is measured annually. \nVE findings should be interpreted as the added benefit of CO VID-19 vaccination in a population \nwith a high prevalence of vaccine- and infection-induced immunity at the start of the 2023-2024 \nrespiratory virus season. \nDr. Link -Gelles presented results from three VE platforms.  VISION is a m ulti-site network of \n>300 emergency departments and urgent cares and >200 hospitals, utilizing a test-negative \ndesign and vaccination status from electronic health records and city and state immunization \nregistries. The IVY Network is a multi -site VE platform that uses a test-negative design with \nvaccination status from electronic medical records, city and state registries, and plausible self-report.  Medicare studies used a retrospective cohort design from Medicare-fee-for -service \nclaims data. \nStudy results presented by Dr. Link -Gelles showed that COVID -19 vaccines protected both \npersons with and without immunocompromise. Patterns of COVID -19 VE in \nimmunocompromised people differed from season to season, with generally lower VE compared \nto non-immunocompromised people but inconsistent waning patterns. During 2023-2024, VE \nagainst hospitalization in immunocompromised people waned to 0 by ~4-6 months. \nIn adults aged ≥65 years, 2023-2024 COVID -19 vaccination provided increased protection \nagainst COVID -19-associated emergency department and urgent care ( ED/UC) visits and \nhospitalizations compared to no 2023-2024 vaccine dose. Protection waned to 0 against \nCOVID -19-associated ED/UC visits and hospitalization by ~4-6 months. Waning patterns of \n2023-2024 COVID -19 vaccines appeared similar to previous COVID -19 vacc ine formulations; \nthe most durable protection appeared to be for critical illness. VE against cri tical illness \nremained above 40% at 5 months after vaccination among adults aged ≥65 years. As with \nprevious COVID -19 vaccine formulations, effectiveness was similar across age groups. Data \nfrom prior seasons show that an additional dose of the same formul a appeared to provide \nadditional protection. \nDr. Chu inquired whether messaging was targeted at providers of patients in long-term facilities \nto increase low vaccine rates in these groups. She also asked whether CDC could measure the \nvaccine's impact on long -term COVID -19. \nDr. Peacock stated that efforts have been made to increase vaccine rates within this group, but \nthey have had limited success. Dr. Link -Gelles said that research on long-term COVID is \nchallenging because its symptoms can resemble those of many other illnesses. Studies have been conducted on this and generally have found some level of protection by vaccination, but results vary across studies. This is an ongoing area of research both by CDC and by other \ngroups. \n27 \n \n   \n \n  \n   \n \n  \n \n  \n  \n  \n  \n \n \n \n \n   \n  \n \n \n \n \n \n \n  \n  \n \n \n \n \n \n  \n \n \n \n \n \n   \n \n \n \n  Dr. Schechter expressed concern for lower vaccination rates among populations ≥65 years of \nage and older and pregnant women. COVID -NET shows that only 15% of adults ≥65 years of \nage received the 2023-24 C OVID vaccine last year, and that of pregnant women whose infants \n6 months of age and younger were hospitalized, fewer than 5% were vaccinated. \nDr. Asturias requested clarity on the difference in rates of COVID-19 outcomes among \nimmunocompromised children on slide 17 of Dr. Taylor’s presentation. The Colorado data show that the rate of hospitalization of healthy children under 1 year of age is relatively high and \ncomparable to adults over 60 years of age.  The children with immunocompromising conditions are probably somewhat older. \nDr. Taylor confirmed that infants under six months are comparable to adults older than 65-74 years of age. There are some differences between the populations, but the immunocompromise \ngroup's sample size is small, and because of that, it was presented as a broader age group. \nMs. Moser thanked the people who submitted comments on this portion of the agenda. She \nunderstands why we are studying the VE and comparing it to last year, but it would be helpful to \nbetter understand the “no recent vaccine” comparison group. It is essential to help people \nunderstand their protection level moving forward. \nDr. Loehr commented that the incidence rate of hospitalization increased with age. It is stunning \nthat 1 in 70 adults will be admitted to the hospital for COVID. He also stated he is torn on the \nrecommendation for 6 months between the first and second doses. Patients want to get the vaccine in July or August because of a trip and are unsure whether they can receive the next \ndose in September. I usually say 4 months, but that does not necessarily meet the 6-month time \nframe. \nDr. Brewer stated that the audience would better follow the presentation if there were language \nto frame VE data on slides 25 and 26 for the final row of 18-64-year -olds. He also asked for \nclarification on how this data should be interpreted. \nDr. Link -Gelles clarified that the “7-299 days earlier” is just an average breakdown for the four \ncategories below. Dr. Brooks stated that the risk for ED/UC visits is increased by about 20% in each category on \nthe same slide. He asked how one interprets the slides and whether the data on this slide reflect \nrelative VE. \nDr. Link -Gelles clarified there is no biological plausibility for a vaccine increasing your risk of \ndisease, so that is not what we think has been happening in the longest time since vaccination. \nVE, at its root, essentially measures the risk of disease in a vaccinated population compared to \nan unvaccinated population. The unvaccinated or less vaccinated group can significantly impact \nthe estimated VE. In this case, unvaccinated people get infected in the 6 months while \nvaccinated people are protected by their vaccine. That raises the infection-induced immunity level in unvaccinated people, which may make the VE look very low when the vaccine has \nwaned, such that vaccinated people are now susceptible. This is a combination of relative and \nabsolute VE. \n28 \n \n  \n  \n \n \n  \n \n \n  \n \n  \n \n \n \n \n   \n \n \n  \n  \n \n \n  \n \n  \n  \n \n \n \n   \n \n  \n   \n  \n \n \n \n \n  Dr. Kuchel commented that chronological age is a good research measure for most adult populations. However, as someone practicing geriatric medicine, chronological age is an \nimperfect measure within older populations. He requested that some VE data be stratified by \nsex in addition to age because men and women do not age similarly. \nDr. Brewer requested an estimate of how much of the waning immunity in the control group is \ndue to natural infection. \nDr. Link -Gelles described that the earlier phenomenon of the population getting infected, which \nresults in lower than expected VE, probably impacts VE more the further away you get from \nvaccination. Measured VE can change quite a bit based on background rates of disease. For \nexample, lower VE will be measured if there is a disease surge the month before a vaccine is introduced and the population has a very high rate of infection-induced immunity. The exact \namount is difficult to quantify, especially since serology is unavailable in most of our studies. \nDr. Lisa Prosser (University of Michigan) presented the economic analysis of an additional dose \nof the 2024– 2025 COVID-19 vaccine. Updates to the current version of the model include a 2-\ndose strategy (an additional mid-year dose), 2023-2024 hospitalization rates (COVID -NET \ndata), CDC -negotiated 2024-2025 prices for vaccine costs , and adjustment of all cost inputs to \n2024 dollars. \nWeekly rates of COVID -19-associated hospitalizations by season for all ages have been \ndeclining in recent years. For the 2023-2024 season, the probability of hospitalization due to \nCOVID -19 illness has dropped for all age groups, ranging from 14% lower in the 65 and older \nage group to 33% lower in the 18-49 year age group compared to the 2022-2023 season. The analysis plan included a base case and uncertainty analyses. The outcomes were stratified \nby intervention strategy and by age subgroups. Vaccination for the 2-dose strategy economic analysis shows that the ICERs for age groups <65 years old were less favorable than those ≥65 \nyears old across plausible parameter ranges. For ≥ 65-year -old age group, ICERs were most \nsensitive to seasonality -adjusted vaccine impact, probability of hospitalization, and vaccination \ncosts. ICERs are more favorable in scenarios with a higher risk of hospitalization and lower \nvaccination costs. \nDr. Shaw questioned whether models accounted for the costs of potential post-infection care, \ne.g., transient or permanent residence in a skilled nursing facility, and the cost of a family \nmember who may need to leave work to care for an elderly adult. \nDr. Prosser responded that the costs associated with hospitalizations and complications are \nfrom MarketScan data, which includes episode cost and some costs paid for by the health plan. \nIt is highly likely that some of those costs would not be incorporated there if they’re covered at \nthe family level. This would include a conservative estimate of those costs. The cost of informal \ncaregiver time, primarily associated with hospitalization, has been included in the model. \nDr. Loehr commented that he buys his vaccines as a small family practice owner. The current \nprices at which he purchases the vaccines are about 30% less than what is listed on the private \nmarket price slide. \n29 \n \n  \n \n  \n \n   \n  \n \n     \n  \n \n \n \n \n \n \n \n \n \n \n  \n  \n \n  \n   \n \n    \n \n \n  \n \n \n \n  \n \n \n   \n \n   \n  \n Dr. Prosser agreed that this was an important point to share. Looking at an approximate $100 \nper dose, for the additional dose strategy, the corresponding incremental cost-effect ratios \nremain above $600,000 per QALY for age groups under 65 years ; perhaps we can get closer to \n$200,000 per QALY for those 65 and older using a lower vaccine cost. \nDr. Schechter reflected on the previous summer's surge, which had higher hospitalizations in \nCalifornia than the 2023 surge.  He asked whether this was reflected in national hospitalization \nstatistics , and about the impact of hospitalization rates on these estimates . \nDr. Taylor responded that COVID -NET is comprised of multiple sites, and each site was \ndifferent. Some sites that had a mild winter had a larger summer surge. Sites with very high rates during the winter peak in December and January saw a more moderate summer surge. \nDr. Brewer requested that Dr. Prosser speak about how equity would be cost-effective and how the model addresses the cost of time loss (e.g., post-vaccine side effects, time off work to receive the vaccine, etc.). \nDr. Prosser stated that there had been no formal incorporation of health equity considerations \ninto the model. Vaccination would be more cost-effective if a population or sub-population had \nhigher rates of illness, hospitalization, or death. This could be a way to think about equity within \nthis presentation. This is not a current goal in this analysis but can be considered in a future \nstudy. Regarding time loss, some costs are incorporated into the time required to receive \nvaccination. \nMs. Lauren Roper (CDC/NCIRD) reviewed the Evidence to Recommendations ( EtR) framework \nfor additional doses of the 2024– 2025 COVID -19 vaccine in older adults and people with \nmoderate or severe immunocompromise. On June 27, 2024, ACIP voted to recommend 2024– \n2025 COVID-19 vaccines for everyone ages ≥6 months. On August 22, 2024, the FDA \napproved and authorized 2024– 2025 Pfizer -BioNTech and Moderna COVID -19 vaccines for \npeople ages ≥6 months. On August 30, 2024, the FDA authorized the 2024– 2025 Novavax \nCOVID -19 vaccine for people ages ≥12 years of age. \nThe EtR framework policy questions are, in addition to previously recommended 2024-2025 \nvaccination: \n• Should a second dose of 2024– 2025 COVID -19 vaccine be recommended for adults \nages 65 years and older? \n• Should a second dose of 2024– 2025 COVID -19 vaccine be recommended for people \nages 6 months and older who are moderately or severely immunocompromised? \n• Should additional doses (i.e., 3 or more) of 2024– 2025 COVID-19 vaccine be \nrecommended for people ages 6 months and older who are moderately or severely \nimmunocompromised under shared clinical decision-making? \nCurrently, the ACIP recommends that people age d ≥5 years receive one dose of the 2024– 2025 \nCOVID -19 vaccine at least 2 months after receiving their last dose. People who are previously \nunvaccinated for COVID -19 and receive Novavax should complete a 2-dose initial series. \nCurrent recommendations for people aged ≥6 months who are moderately or severely \nimmunocompromised include a homologous initial COVID -19 vaccine series with at least 1 \n2024– 2025 COVID-19 vaccine dose, and they may receive one additional 2024– 2025 COVID -\n19 vaccine dose with an option for further additional doses of 2024– 2025 COVID -19 vaccine \ninformed by the clinical judgment of a healthcare provider and personal preference and \ncircumstances. \n30 \n \n  \n \n \n \n  \n \n \n \n \n \n \n  \n  \n \n \n   \n \n \n    \n  \n \n  \n  \n \n \n \n   \n \n \n  \n  \n \n  Regarding the public health problem, Ms. Roper shared that SARS -CoV-2 continues to circulate \nyear-round, with peaks occurring in the winter and late summer, compared to influenza and \nRSV, which have clearer increases during the typical respiratory virus months, with periods of \nlow activity during the summer . Adults ≥65 years of age have the highest rates of \nhospitalizations due to COVID -19. Older adults also have the highest rates of death due to \nCOVID -19. Adults ≥65 years of age have higher vaccination- only seroprevalence rates than \nyounger age groups . Hospitalizations are highest among American Indian/Alaska Native non-\nHispanic persons, followed by Black non-Hispanic persons, and are lowest among Asian and \nPacific Islander non-Hispanic persons. The number of chronic conditions a person has \nincreases with increasing age and is higher among Black non-Hispanic persons than among other racial and ethnic groups. About 1 in 6 people hospitalized with CO VID-19 have an \nimmunocompromising condition. Risk for severe outcomes during COVID –19–associated \nhospitalization among adults varies by immunocompromising condition status. After reviewing \nthis domain, the work group felt COVID-19 disease among adults ≥65 years of age and among \npeople with moderate or severe immunocompromise is of public health importance. \nFor benefits and harms, adults ≥65 years of age who received a 2023– 2024 COVID -19 \nvaccination had increased protection against COVID -19-associated ED/UC visits and \nhospitalizations compared to people who had not received a 2023– 2024 vaccine dose. \nProtection waned to 0 against COVID -19-associated ED/UC visits and hospitalization by ~4-6 \nmonths. Waning patterns of 2023– 2024 COVID -19 vaccines appeared similar to previous \nCOVID -19 vaccine formulations; most durable protections appeared for critical illness. VE \nagainst critical illness remained above 40% at 5 months after vaccination among those ≥65 \nyears of age. VE was similar across age groups. Data from prior seasons shows that an \nadditional vaccine dose appeared to provide some extra protection. Updated COVID -19 \nvaccination helped protect COVID -19–related thromboembolic events. Based on modeling data, \nannual and semiannual COVID -19 vaccine doses are likely to have the largest benefit in adults \n≥65 years of age and people who are immunocompromised. \nCOVID -19 vaccines protected persons both with and without immunocompromise. Patterns of \nCOVID -19 VE in immunocompromised persons differed from season to season, with generally \nlower VE than non-immunocompromised person s but with inconsistent waning patterns. During \n2023– 2024, VE against hospitalization in people with immunocompromising conditions waned \nto 0 by ~4-6 months. The inconsistency in waning patterns is likely multifactorial, including \nheterogeneity among those classified as immunocompromised, variation in underlying immunity \nand response to prior infection, and differing health behaviors over time and by \nimmunocompromised status. \nSafety surveillance demonstrated that serious adverse events after COVID -19 vaccination have \nbeen rare. Anaphylactic reactions have been rarely reported following receipt of COVID -19 \nvaccines. There is a rare risk of myocarditis and pericarditis; however, this is predominately in \nmales ages 12-39 years. No increased risk has been observed in adults aged ≥65 years. \nWhether the risk might be different in immunocompromised people is unknown. COVID -19 \nvaccine doses continue to be reactogenic. The rate of local and systemic reactions reported to V-safe was lower with additional doses than after the initial series. Most vaccine recipients have mild reactions, but during 2023– 2024, at least 10% reported health impact events during the 7 \ndays post- vaccination, such as being unable to complete daily activities. Symptoms are less \nfrequent and severe among older adults than adolescents and younger adults. \n31 \n \n   \n \n \n  \n \n \n \n \n \n \n \n \n \n  \n \n   \n \n  \n \n \n \n \n \n \n  \n \n \n \n \n  \n  \n \n \n \n \n      \n  \n \n  \n \n After reviewing this domain, the work group felt that the desirable anticipated effects of a second \ndose of 2024– 2025 COVID -19 vaccine in adults ages ≥65 years were moderate to large. The \nwork group majority felt that the undesirable anticipated effects of a second dose of a 2024– 2025 COVID-19 vaccine in adults ages ≥65 were small, with a minority choosing minimal. The work group felt that the balance of benefits and harms favored the intervention of a second dose in this group. The work group felt that the desirable anticipated effects of a second dose of 2024– 2025 COVID-19 vaccine in people with moderate or severe immunocompromise was \nmoderate. The work group majority thought that the undesirable anticipated effects of a second \ndose of 2024– 2025 COVID-19 vaccine in people with moderate or severe immunocompromise \nwere small, with a minority polling minimal. The work group felt that the balance of benefits and \nharms favored the intervention of a second dose in this group. The work group felt that the desirable anticipated effects of a third dose of 2024– 2025 COVID -19 vaccine in people with \nmoderate or severe immunocompromise was moderate. The work group majority thought that \nthe undesirable anticipated effects of a third dose of 2024– 2025 COVID -19 vaccine in people \nwith moderate or severe immunocompromise were minimal to small. The work group was split \nbetween the balance of benefits and harms, favoring the intervention and being unclear. \nFor the values domain, adults ≥65 years of age surveyed were more concerned about COVID -\n19 disease and had higher confidence in vaccine safety and vaccine importance. The work \ngroup felt “moderately” that adults ≥65 years of age feel the desirable effects are large relative \nto undesirable effects. The work group opinion was split between “probably important uncertainty or variability” and “probably not important uncertainty or variability” in how adults ≥65 \nyears of age value the main outcome. Limited data exists on the concern about COVID -19 \ndisease, specifically in people with moderate or severe immunocompromise. The work group \nopinion was moderate to large that people with moderate or severe immunocompromise feel the \ndesirable effects are large relative to undesirable effects. The work group opinion was split \nbetween “probably important uncertainty or variability” and “probably not important uncertainty or variability” in that people with moderate or severe immunocompromise value the main outcome. \nFor the acceptability domain, the percent vaccinated with 2023– 2024 COVID -19 vaccine \ncoverage was higher for adults ≥65 years of age compared to younger age groups. 39.3% of \nadults aged ≥65 years and 5.4% of immunocompromised adults received at least two 2023– \n2024 vaccine doses. A healthcare provider recommendation for the COVID -19 vaccine was \nhighest among adults ≥65 years of age. In an October 2024 survey of healthcare providers, \n70% of respondents reported recommending a second COVID -19 vaccination to el igible \npatients ≥65 years of age “most of the time“ or “always” and 68% reported recommending a \nsecond COVID-19 vaccination to eligible patients who were immunocompromised “most of the time” or “always.” Feedback through the work group professional organization liaisons indicated they prefer age-based recommendations over risk -based or shared clinical decision- making, \nfrequent changes in vaccine recommendations create confusion, most preferred one to two total doses a year, and need to reiterate that self-a ttestation of being moderately or severely \nimmunocompromised is permissible. \n2023– 2024 COVID-19 vaccine coverage of ≥2 doses among adults aged ≥65 years of age \nvaried by race, ethnicity, and urbanicity. Coverage was higher in Black, non-Hispanic adults \ncompared to white, non-Hispanic adults. Coverage was also higher in urban settings compared \nto rural. 2023– 2024 COVID -19 vaccine coverage of ≥2 doses among immunocompromised \nadults ≥18 years varied by urbanicity, race and ethnicity, healthcare provider recommendation, and insurance status. Coverage was lower in Asian adults compared to white, non-Hispanic \nadults. It was also higher in suburban areas compared to rural areas. \n32 \n \n  \n \n \n  \n  \n \n  \n \n \n  \n \n \n \n \n \n \n \n  \n   \n \n \n  \n \n \n  \n \n \n   \n \n \n  \n  \n \n \n \n \n \n  Coverage was higher among people with health insurance and among those with a healthcare \nprovider recommendation. \nWhen asked if recommending a second dose of the 2024– 2025 COVID -19 vaccine for adults \nages ≥65 years of age would be acceptable to key stakeholders, the work group’s opinion was \n“probably yes” and “yes.” When asked if recommending a second dose of the 2024– 2025 \nCOVID -19 vaccine for people ages ≥6 months with moderate or severe immunocompromise \nwould be acceptable to key stakeholders, the work group’s opinion was “probably yes” and \n“yes.” When asked if recommending additional doses (i.e., three or more) of the 2024 – 2025 \nCOVID -19 vaccine for people ages ≥6 months with moderate or severe immunocompromise \nwould be acceptable to key stakeholders, the work group’s opinion was “probably yes” and \n“yes.” \nFor the feasibility domain, based on survey data, physicians think shared clinical decision-\nmaking (SCDM) increases time and confusion. When asked if a second dose of 2024– 2025 \nCOVID -19 vaccine was feasible to implement among adults ≥65 years of age, the work group’s \nopinion was “yes,” with a minority saying, “probably yes.” When asked if a second dose of 2024– 2025 COVID -19 vaccine is feasible among persons with moderate or severe \nimmunocompromise, the work group’s opinion was split between “probably yes” and “yes.” \nWhen asked if additional doses (i.e., three or more) of 2024– 2025 COVID-19 vaccine were \nfeasible to implement among persons with moderate or severe immunocompromise, the work group’s opinion was split between “yes” and “probably yes”. \nIn the resource use domain, administering a second dose of the COVID -19 vaccine is most \ncost-effective for older adults, who experience the highest disease burden. An additional dose is \nlikely more cost-effective in populations with a higher prevalence of risk factors. There was no \ninformation specific to the cost-effectiveness of additional doses in people with moderate or \nsevere immunocompromise. When asked if a second dose of the 2024– 2025 COVID-19 \nvaccine in adults ≥65 years old is a reasonable and effi cient allocation of resources, the work \ngroup answered “yes” and “probably yes.” When asked if a second dose of the 2024– 2025 \nCOVID -19 vaccine in persons ≥6 months of age with moderate or severe immunocompromise \nwas a reasonable and efficient allocation of resources, the work group answered “yes” and “probably yes.” When asked whether additional doses (i.e., three or more) of the 2024 – \n2025 COVID -19 vaccine in persons ≥6 months of age with moderate or severe \nimmunocompromise would be a reasonable and efficient allocation of resources, the work \ngroup’s opinion was split between “probably no,” “probably yes,” “varies” and “don’t know.” \nThe work group felt that a harmonized recommendation for older adults and \nimmunocompromised people would ease implementation. Still, some work group members did \nnot favor a harmonized recommendation but supported differing recommendations in the two \npopulations under consideration. Limited data for immunocompromised people makes making \nrecommendations challenging. Despite hesitations about a shared clinical decision-making \nrecommendation, many work group members acknowledged the benefit for people with \nmoderate or severe immunocompromise. Allowing flexibility in additional doses may allow these patients to time around travel, life events, chemotherapy, etc. \nThere was a low uptake of more than one dose of the 2023– 2024 vaccine. The complexity of \nthe existing schedule has led to reduced adherence by clinicians. Provider recommendations \ndirectly impact uptake, and as part of this recommendation, provider educati on and ensuring \nproviders are on board is critical to improving adherence. More straightforward vaccine recommendations may increase vaccine uptake. \n33 \n \n  \n  \n \n \n \n \n  \n \n \n \n \n \n \n \n \n \n \n  \n  \n \n \n \n  \n \n \n  \n \n   \n  \n \n  \n \n \n \n   \n Focusing on the number of doses of 2024– 2025 vaccine rather than additional doses in \nrecommendations could help reduce complexity and improve uptake. \nThe proposed voting language is as follows: \nIn addition to previously recommended 2024– 2025 vaccination: ACIP recommends a \nsecond dose* of 2024– 2025 COVID-19 vaccine for adults ≥65 years. ACIP recommends \na second dose** of 2024– 2025 COVID-19 vaccine for people ages 6 months –64 years \nwho are moderately or severely immunocompromised. ACIP recommends additional \ndoses (i.e., 3 or more doses) of 2024– 2025 COVID-19 vaccine for people ages 6 months \nand older who are moderately or severely immunocompromised under shared clinical decision-making \n*If previously unvaccinated and receiving Novavax, 2 doses are recommended as initial vaccination series followed by a third dose of any age-appropriate 2024– 2025 \nCOVID -19 vaccine 6 months (minimum interval 2 months) after second dose. \n**If previously unvaccinated or receiving initial vaccination series, at least 2 doses of 2024– 2025 \nvaccine are recommended, and depending on vaccination history more may be needed. This \nadditional 2024– 2025 vaccine dose is recommended 6 months (minimum interval 2 months) \nafter completion of initial vaccination series. \nDr. Lakshmi Panagiotakopoulos (CDC/NCIRD) shared the clinical considerations. The routine schedule is the schedule for people without moderate or severe immune \ncompromise. The proposed recommendations for adults ages 65 years and older are for two \ndoses of 2024– 2025 COVID -19 vaccine at a recommended interval of 6 months (and a \nminim um interval of 2 months). Having a recommended and minimum interval is standard for all \nvaccines and additionally allows for some flexibility in the timing of doses. For those adults 65 and older who have never received a COVID -19 vaccine and are receiving their first dose of \nNovavax vaccine, two doses are recommended as their initial vaccination series, followed by a third dose of any age-appropriate COVID -19 vaccine 6 months after their second dose, with the \nsame 2-month minimum interval.  \nPeople with moderate or severe immune compromise ages 6 months and older are \nrecommended to get an initial COVID-19 vaccine series – this consists of 3 homologous mRNA \nCOVID -19 vaccine doses or 2 Novavax COVID- 19 vaccine doses. The proposed \nrecommendation for 2024– 2025 COVID -19 vaccine doses is for at least two doses with a \nrecommended interval of 6 months and a minimum interval of 2 months. One of these two doses may be a part of the initial vaccination series, and at least 1 of the 2 doses should be recei ved 6 months after completion of the initial series. Beyond that, the additional doses for \n2024– 2025 COVID-19 vaccine would remain under shared clinical decision-making 2 months \nafter the last dose of 2024– 2025 COVID -19 vaccine. \nWhen transitioning from a younger to an older age group, the CDC recommends that people receive the age-appropriate vaccine product and dosage based on their age on the day of vaccination, which is consistent with CDC’s General Best Practices for Immunization. \nSpecifically, if a person moves up to an older age group between vaccine doses, they should receive the vaccine product and dosage for the older age group. The previous option to administer a lower dosage is no longer authorized for children who transition from age 4 to 5 and for children moderately or severely immunocompromised who transition from 11 to 12. \n34 \n \n   \n \n \n \n \n  \n \n \n \n \n \n  \n \n  \n \n  \n \n \n \n \n \n \n  \n \n \n \n \n \n   \n \n \n  \n   \n The main interchangeability language remains the same – in which COVID -19 vaccine doses \nfrom the same manufacturer should be administered whenever recommended. However, there \nare circumstances in which vaccines from different manufacturers may be administered, \nincluding the same vaccine not being available at the time of the clinic visit, the previous dose unknown, a person who would not otherwise receive a vaccine dose, and a contraindication to previously received COVID -19 vaccine. Of note, a VAERS report is not indicated in these \ncircumstances, meaning these are not considered errors. People ages 12 years and older who initiate vaccination with Novavax and receive the first dose of Novavax should complete a 2 \ndose initial series with Novavax vaccine. However, if more than 8 weeks have elapsed since \nreceipt of the first dose, any 2024– 2025 COVID -19 vaccine may be administered. As a \nreminder, COVID -19 vaccine is recommended for everyone ages 6 months and older, \nregardless of prior symptomatic or asymptomatic SARS- CoV-2 infection, including people with \nlong COVID . People who recently had SARS CoV -2 infection may consider delaying a COVID -\n19 vaccine dose by 3 months from symptom onset or positive test if the infection was asymptomatic. Individual factors, such as risk of severe COVID-19 and current indicators of community transmission, should be considered when determining whether to delay getting a \nCOVID -19 vaccination after infection. \nThe interim Clinical Considerations for Use of COVID-19 Vaccines in the United States \nwebpage continues to be rapidly updated to reflect the most recent COVID -19 vaccine \nguidance. COVID-19 vaccine recommendations have moved towards simplicity and the standard language used for the ACIP routine immunization schedule and General Best \nPractices. Recommendations for additional doses in older adults and people with moderate or severe immunocompromise will be updated following the October 2024 ACIP meeting votes. \nDr. Loehr thanked the public for the emails and comments on this topic. There has been a \nstrong push to offer the vaccine to anyone who wants it, not just to individuals ≥65 years of age and immunocompromised. Individuals who care for ill family members are requesting additional vaccine doses. I am not comfortable with that. If an individual is willing to pay for an extra dose \nout of pocket for off-label use of a vaccine, I do not see a reason why they should not be able to \ndo so. \nDr. Panagiotakopoulos responded that this did come up in the work group discussion. The two \nconsiderations were that this is not done for other vaccines and the cost from a societal perspective. It would be unusual to have this done for the COVID -19 vaccines when it is not \ndone for other vaccinations.  \nDr. Wharton clarified that paying out- of-pocket for off-label use of vaccines is generally allowed \nas part of medical practice. \nDr. Asturias questioned whether language should include anything about the ideal time before \nsurges or whether this should be left to others' discretion. \nDr. Panagiotakopoulos replied that considerations for the 6-month recommendation included \nwaning, cost -effectiveness, feasibility , values, and attitudes ; some providers who take care of \nimmunocompromised patients expressed that annual vaccination would be sufficient because of \nthe difficulty of vaccinating more than once a year.  The two-month minimum interval provides \nflexibility , allowing local and personal factors to be considered. \n35 \n \n   \n \n \n   \n \n \n \n \n \n \n  \n \n \n \n  \n \n \n \n \n \n \n \n \n \n \n    \n  \n \n \n   \n \n \n \n \n   \n \n Dr. Cineas requested clarification on the interim clinical considerations, whether the guidance \non the interchangeability slide refers to children 6 months to 4 years old, and whether this \nshould be added for clarity. \nDr. Panagiotakopoulos stated that in addition to 6 months to 4 years, this also applies to \nimmunocompromised people, people who are recommended to get a homologous series, and people receiving Novavax and who were previously unvaccinated. \nMs. Moser added that some people who were caregivers of high-risk people commented on the \npublic forum and stated that they could not get the vaccine when they were willing to pay out of pocket. If this is allowed, we should ensure the providers and pharmacists know they can provide them. There were also educators and parents of young children concerned that the families would get the vaccine in the fall and would have to wait a whole year to get it again. \nWhen people are infected, they can defer for three months, but now we are saying vaccination \nafter six months. \nDr. Fleming-Dutra clarified that while off-label vaccinations are allowed under the practice of \nmedicine, some complexities make it difficult, and this will be discussed in a later session. In \ncertain jurisdictions, there are places where vaccines cannot be given if they are not ACIP -\nrecommended. Although physicians may be able to prescribe it off-la bel, patients may have \ndifficulty accessing said vaccine. Specific to COVID-19, vaccines must be used in alignment \nwith HHS guidance. \nDr. Shaw requested clarification on which group the statement: \"Individual factors such as the \nrisk of severe COVID -19 and current indicators of community transmission should be \nconsidered when determining whether to delay getting a COVID -19 vaccination after infection.\" \nThe vaccine may be ineffective if vaccinated too soon. \nDr. Panagiotakopoulos explained that the statement is not aimed at any specific group. Much of the data is based on low reinfection rates during the first three months following an infection. \nWhile some may contemplate delaying the vaccine, receiving it sooner than three months after your infection is possible. \nDr. Chu concurred with Dr. Shaw that the two months in one slide and three months in the other \nare confusing. Should we instead change the three-month recommendation to “should receive \ntwo doses of the age-appropriate vaccine spaced six months apart as close as three months \nafter the last” to align the language? \nDr. Fleming-Dutra clarified that the FDA determines this two-month minimum interval. Dr. \nKaslow said they would take this point of two- and three-month intervals between vaccination \nand infection causing confusion under advisement. \nDr. Loehr motioned that ACIP recommends a second dose of 2024– 2025 COVID -19 vaccine for \nadults 65 years of age and older. \nDr. Jam ieson seconded the motion. \nDr. Loehr motioned that ACIP recommends a second dose of 2024– 2025 COVID -19 vaccine for \nmoderately or severely immunocompromised people ages 6 months to 64 years. \nDr. Jam ieson seconded the motion. \n36 \n \n  \n   \n  \n \n \n \n \n \n \n \n \n \n \n \n \n     \n \n \n \n \n \n \n \n \n  \n \n    \n   \n \n \n   \n  \n \n \n   \n \n  \n    \n     \n \n     \n \n         \n      \n \n \n  Dr. Loehr motioned that ACIP recommends additional doses (i.e., three or more doses) of 2024– 2025 COVID-19 vaccine for people ages 6 months and older who are moderately or \nseverely immunocompromised under shared clinical decision-making. \nDr. Jam ieson seconded the motion. \nMs. Hayes inquired whether the current vaccine is not 100% aligned with circulating strains of \nthe virus and whether data was available to speak to this. \nDr. Silk stated he does not have specific data from the lab but is told they are expected to \nprovide good protection given that they are subsets and the sublineages of the JN.1 strain. \nSpeaking on behalf of the American Geriatrics Society, Dr. Schmader expressed support for the \nrecommendation for an additional dose for those ≥65 years . The AGS also notes that a n \nimportant population likely to benefit from additional doses that is not included in these \nrecommendations is nursing home residents younger than 65 years of age. This is something to \nconsider. \nDr. Hopkins commented that vaccines are the best defense against respiratory diseases, yet our vaccination rate remains below our goals. Less than 1 in 5 adults are concerned about Flu, COVID -19, or RSV. Only 38% shared they would get a Flu vaccine, and 26% would “definitely \nget” an updated COVID vaccine. The concerns included side effects and distrust of vaccines in general. To address this problem, it’s necessary to directly address the concerns of side effects and safety . \nVote: COVID-19 Vaccines-Vote #1 \nDr. Keipp Talbot (ACIP Chair ) read the following proposed ACIP voting language for COVID -\n19 vaccines into the record: \nIn addition to previously recommended 2024-2025 vaccination: ACIP recommends a second dose of 2024-2025 COVID -19 vaccine for adults ages 65 \nyears and older \nMotion/Vote: COVID -19 Vaccines \nDr. Loehr motioned to approve the proposed vote recommendation for COVID -19 vaccines vote \n#1, stating,” ACIP recommends a second dose of 2024-2025 COVID -19 vaccine for adults ages \n65 years and older.”  Dr. Jamieson seconded the motion. No COIs were declared. The motion \ncarried with 15 favoring and 0 opposing. The disposition of the vote was as follows: \n15 Favored: Asturias, Brewer, Brooks , Chen, Chu, Cineas, Jamieson, Kamboj, Kuchel, \nLoehr, Maldonado, Moser, Schec hter, Shaw and Talbot \n0 Opposed:\n0 Abstained: \n37 \n \n   \n \n    \n   \n \n \n  \n \n \n \n   \n \n   \n  \n   \n \n    \n \n         \n      \n \n  \n \n    \n   \n \n \n   \n  \n \n \n \n   \n \n   \n  \n    \n \n \n       \n \n         \n      \n \n \n  Vote: COVID-19 Vaccines-Vote #2 \nDr. Keipp Talbot (ACIP Chair ) read the following proposed ACIP voting language for COVID -\n19 vaccines into the record: \nIn addition to previously recommended 2024-2025 vaccination: \nACIP recommends a second dose of 2024-2025 COVID -19 vaccine for people ages 6 \nmonths -64 years who are moderately or severely immunocompromised \nMotion/Vote: COVID -19 Vaccines \nDr. Loehr made a motion to approve the proposed vote recommendation for COVID -19 \nvaccines vote #2, ”ACIP recommends a second dose of 2024– 2025 COVID-19 vaccine for \npeople ages 6 months -64 years who are moderately or severely immunocompromised.”  Dr. \nJamieson seconded the motion. No COIs were declared. The motion carried with 15 favoring \nand 0 opposing. The disposition of the vote was as follows: \n15 Favored: Shaw, Schec hter, Moser, Maldonado, Loehr, Kuchel, Kamboj, Jamieson, \nCineas, Chu, Chen, Brooks, Brewer, Asturias, Talbot \n0 Opposed:\n0 Abstained: \nVote: COVID-19 Vaccines-Vote #3 \nDr. Keipp Talbot (ACIP Chair ) read the following proposed ACIP voting language for COVID -\n19 vaccines into the record: \nIn addition to previously recommended 2024-2025 vaccination: ACIP recommends additional doses (i.e., 3 or more doses) of 2024– 2025 COVID -19 \nvaccine for people ages 6 months and older who are moderately or severely \nimmunocompromised under shared clinical decision-making \nMotion/Vote: COVID -19 Vaccines \nDr. Loehr made a motion to approve the proposed vote recommendation for COVID -19 \nvaccines vote #3, ”ACIP recommends additional doses (i.e., 3 or more doses) of 2024– 2025 \nCOVID -19 vaccine for people ages 6 months and older who are moderately or severely \nimmunocompromised under shared clinical decision-making.”  Dr. Jamieson seconded the motion. No COIs were declared. The motion carried with 15 favoring and 0 opposing. The \ndisposition of the vote was as follows: \n15 Favored: Asturias, Brewer, Brooks , Chen, Chu, Cineas, Jamieson, Kamboj, Kuchel, \nLoehr, Maldonado, Moser, Schec hter, Shaw and Talbot \n0 Opposed:\n0 Abstained: \n38 \n \n  \n \n   \n   \n  \n    \n \n \n \n \n \n \n \n  \n \n  \n  \n \n  \n \n \n \n  \n  \n \n \n \n \n \n \n  \n \n \n \n \n \n \n  \n \n PUBLIC COMMENTS \nThe floor was opened for public comment on October 23, 2024, at 3:45 PM E ST. The comments \nmade during the meeting are summarized in this document. Members of the public were also \ninvited to submit written public comments to ACIP through the Federal eRulemaking Portal \nunder Docket Number ID CDC-2024-0072. Visit regulations.gov for access to read the \ncomments received. \nNoah Louis-Ferdinand \nVoices for Vaccines \nNoah Louis -Ferdinand, communications coordinator for Voices for Vaccines, commented on \nadding the high-dose flu vaccine to the V FC program for transplant recipients. He emphasized \nthe importance of protecting vulnerable populations, noting low vaccination rates among young, \nhealthy individuals. Many of his peers in their 20s are not enthusiastic about getting vaccinated, making additional options beneficial. He also expressed interest in the expanded pneumococcal vaccination recommendations, questioning how likely adults are to receive multiple vaccines in a year. He highlighted the importance of understanding the need for multiple vaccinations and \nthe potential barriers, such as time off for appointments and the possibility of feeling unwell \nafterward. These public health considerations are crucial for effective implementation, even though the safety and efficacy of these vaccines are established. \nAndrew Wang, PhD\nPrivate Citizen \nAndrew Wang thanked Dr. Talbot, the committee members, and the public for the opportunity to \nshare his comments. He highlighted ongoing concerns regarding the COVID -19 pandemic, \nwhich still affects millions of Americans. He stressed the need for access to vaccines at least \ntwice a year for all individuals, regardless of health status, and urged the committee to revise \ntheir policy questions accordingly. A restrictive approach to vaccination creates confusion and \ndiscourages high-risk populations, including those under 65, from seeking necessary boosters. \nHe pointed out that public vaccine hesitancy will persist if the committee complicates vaccination criteria. Moreover, the vaccination schedule should address waning efficacy and new variants, aligning with the FDA’s approach. Ensuring biannual vaccine access will enhance protection against severe outcomes and align with CDC recommendations. He also emphasized \nthe need for equitable and affordable access to vaccines, especially after the end of the CDC’s Bridge Access program in August 2024, which left many uninsured with limited access . He \nurged the committee to support no-cost access to COVID -19 vaccines to eliminate barriers and \nimprove public health. \nPaul Hennessy \nUnaffiliated Community Member \nPaul Hennes sy said that the CDC must allow everyone to receive a second COVID -19 shot two \nmonths after the first rather than limiting it to immunocompromised individuals. He requested \nchanges to voting language to broaden eligibility, as restricting access creates barriers and \nlimits protection. Additional shots have been proven effective and safe, and the CDC should \nmake sure this is covered by insurance while restoring the Bridge Access Program. Given the immune damage caused by COVID -19 in the population, all individuals need access to extra \ndoses. \n39 \n \n   \n  \n  \n \n   \n \n \n \n \n  \n \n \n  \n \n \n \n \n \n \n \n \n \n  \n \n  \n \n \n  \n \n \n \n  \n \n \n   \n \n  \n \n \n  \n The CDC has noted spikes in cases during summer and winter, suggesting that low \ntransmission periods are not as low anymore—a more frequent vaccination strategy with \nupdated vaccine every six months is needed, rather than just in the fall. Waning vaccine efficacy should also be investigated. The ACIP should accelerate funding for intranasal COVID -19 \nvaccines and ensure H5N1 vaccines are available to all, especially farmers. Annual H5N 1 \nvaccinations alone will not suffice; preventative vaccines are essential for public health. \nEdward Nirenberg\nUnaffiliated Community Member \nEdward Nirenberg thanked ACIP for the opportunity to speak. Despite advancements in other \nareas, he expressed concern over the stagnation of influenza vaccine innovation. He noted that most available vaccines are ineffective against the H3N2 virus, partly due to egg-based \nproduction methods. He urged increased support at the clinical trial, regulatory, and \nmanufacturing level to modernize influenza vaccines and highlighted the increasing public \ndiscomfort with injections. He suggested that combining vaccine and mucosal -administered \noptions might be more acceptable. He supported the FDA's decision to allow caregiver and self-\nadministration of FluMist. He also discussed the durability of antibodies from current vaccines, \nincludi ng mRNA options, and advocated for making additional vaccine doses available. He \nemphasized the need for clear communication regarding the risks and benefits for those \nconsidering extra COVID -19 vaccines. He also noted that immunocompromised individuals want \nadditional doses but need help finding suitable vaccination environments, feeling uncomfortable in crowded, poorly ventilated pharmacies. \nTimothy Cestaro\nUnaffiliated Community Member \nTimothy Cestaro thanked the group for the opportunity to share his concerns. As a father of four \nboys, he reported that his first three children were vaccinated without issues. Still, his youngest \nson suffered severe complications due to his pediatrician’s failure to follow safety protocols. He \nworried about the lack of communication regarding vaccination safety for children with existing health issues. His son experienced severe allergic reactions and was diagnosed with eczema, which the pediatrician suggested was safe for vaccination. Despite being immunodeficient by CDC standards, the child received live vaccines at an early age and later had a febrile seizure after vaccination. He expressed concern that MMRV should not be given due to the risk of \nfebrile seizures. He also criticized the FDA for approving two vaccines that offer similar immunity when one has proven more dangerous, emphasizing that these decisions should not rest solely with parents. \nDaniel Bessonov \nMasks for All \nDaniel Bessonov thanked the group for the opportunity to share his views. He strongly \nencourages the CDC to recommend COVID -19 vaccines for all ages and health statuses, \nadvocating for at least two vaccinations annually . Full access to spring vaccinations is essential, \nas the virus persists year -round and often surges. Immunity from vaccines wanes significantly \nwithin 4 to 6 months, increasing the risk of infection and complications. Restricting vaccines based on age and health status leaves many unprotected, raising the chances of transmission. Regular updates to the vaccine are necessary to maintain effectiveness. He has faced \nvaccination barriers due to his health, placing him at higher risk. \n40 \n \n   \n  \n \n \n \n \n \n \n \n   \n \n \n \n \n   \n \n \n    \n \n \n  \n  \n \n   \n \n \n  \n \n \n \n \n \n \n \n \n \n  \n  \n \n \n \n \n  The low vaccination rates compared to influenza are concerning. Continuous widespread \nvaccination is crucial, as relying on infection immunity is risky. Frequent vaccination is vital to \nprevent serious long-term health issues related to l ong COVID. The current vaccination \nrestrictions are confusing and may discourage people from getting needed boosters. \nCorey Greenblatt, MPH\nGlobal Healthy Living Foundation \nCorey Greenblatt, representing the Global Healthy Living Foundation, expressed support for \nvaccine access and public trust in their safety but raised concerns about specific RSV and PCV vaccine guidelines proposed by the committee. He hopes for revisions before finalization. The foundation advocates for individuals with chronic diseases, especially the most vulnerable, for whom vaccine access is essential. The recommended RSV vaccine for those aged 60 to 74 \nposes significant implementation challenges, particularly in community settings. The \nrequirement to confirm immunocompromised status may be hindered by inaccessible medical records. While the ACIP suggests patient attestation for risk factors, this can complicate the healthcare providers' decision-making process. Providers should not have to set aside their \nclinical judgment. Aligning recommendations with FDA guidelines could help ensure informed \ndecision-making while maintaining patient safety. Additionally, the foundation urges routine PCV \nrecommendations for all adults over 50 to address alarmingly low pneumococcal vaccination rates. \nRESPIRATORY SYN CYTIAL VIRUS (RSV) VACCINES -MATERNAL/PEDIATRIC \nDr. Helen Chu (ACIP, Work Group Chair) introduced the Respiratory Syncytial Virus (RSV) \nsection.  As of last year, there are now two forms of protection for infants against RSV. They are \nmaternal vaccine ( ABRYSVO\n®, Pfizer) and n irsevimab (Beyfortus®, Sanofi & AstraZeneca). The \nmaternal vaccine is administered at 32- to 36 weeks gestation. Nirsevimab is administered to all \ninfants ≤8 months whose mother did not receive maternal vaccine. Only one of these products \nis needed in most instances. Nirsevimab and maternal vaccines have different seasonal administration windows to provide optimal protection to the infant. The maternal vaccine is \ntypically administered from September through January. For infants born shortly before October \nor during October through March who are not protected by the maternal RSV vaccine, immunize \nwithin one week of birth, ideally during the birth hospitalization. \nDr. Anushua Sinha (Merck) presented on clesrovimab (MK -1654). Clesrovimab binds with high \naffinity to RSV F protein site 4 with a highly conserved binding epitope. It has a low rate of \nmutations detected within its binding site sequences. It has a high potency in vitro against various RSV clinical isolates and is equipotent against RSV -A and RSV -B. Three engineered \nsubstitutions termed YTE result in an extended half-life. It achieves high nasal tissue distribution \nand concentrations at sites of RSV infection. \nThe proposed indication is the prevention of RSV lower respiratory tract disease in neonates \nand infants who are born during or entering their first RSV season with a proposed dose of 105 mg administered as a single intramuscular (IM) injection at the same dose to all infants \nregardless of weight. \nProtocol 004 was a Phase 2b/3 double-blinded, randomized, placebo-controlled study in healthy \npreterm and full -term infants. The study's endpoints were the vaccine's safety, tolerability, and \nefficacy against medically -attended lower respiratory tract infection due to RSV. \n41 \n \n  \n  \n   \n \n  \n  \n \n \n  \n \n \n \n  \n   \n \n \n \n \n \n \n \n \n  \n  \n \n \n \n \n \n \n \n \n  \n \n \n \n  \n \n \n  Clesrovimab, administered as a single dose for infants of all weights, provides robust protection \nagainst mild, moderate, and severe RSV disease for all healthy infants, including term and \npreterm. Clinical data demonstrates over 90% efficacy in preventing RSV-associated lower \nrespiratory tract (LRI) hospitalizations through 6 months. Clesrovimab efficacy is durable across \nall efficacy endpoints through 6 months. No shifting of RSV disease burden was seen in the \nsecond RSV season. Clesrovimab is well tolerated in healthy preterm and full -term infants born \nduring or entering their first RSV season, and it has a safety profile that is generally comparable \nto that of a placebo. \nProtocol 007 is a Phase 3 multicenter, randomized, partially blinded palivizumab-controlled trial \nconducted with active surveillance over 2 RSV seasons. The participants were infants at an increased risk for severe RSV disease. This is an ongoing study. The endpoints are safety, tolerability, and efficacy. \nThe safety profile of clesrovimab in infants at increased risk of severe RSV disease is generally \ncomparable to palivizumab and consistent with the safety profile in healthy infants. Efficacy in the Protocol 007 population was inferred from efficacy established in Protocol 004 among healthy infants based on comparable clesrovimab pharmacokinetic data. In infants at increased \nrisk for severe RSV disease, a single dose of c lesrovimab protects against RSV disease, \nincluding RSV hospitalization, through 6 months. \nIn conclusion, clesrovimab, administered as a single dose for infants of any weight, provides \nrobust protection against mild, moderate, and severe RSV disease for all infants, including term, preterm, and those with risk factors. Clesrovimab is highly efficacious in healthy infants against \na broad spectrum of RSV disease endpoints, with no shifting of RSV disease burden in the \nsecond RSV season (Protocol 004) —over 90% efficacy in preventing RSV LRI hospitalizations \nthrough 6 months. Clesrovimab also protects infants at increased risk for severe RSV disease, comparably to palivizumab (Protocol 007). \nClesrovimab is well -tolerated in infants, with a safety profile generally comparable to controls \nand consistent across infant populations. It is well tolerated in healthy preterm and full -term \ninfants born during or entering their first RSV season, and its safety profile is generally \ncomparable to that of placebo. The safety profile of clesrovimab in infants at increased risk for severe RSV disease is usually comparable to palivizumab and consistent with the safety profile in healthy infants. \nDr. Jamieson inquired whether it was possible to stratify efficacy by infant weight since the \nconclusion was robust protection across all infant weights. \nDr. Sinha responded that the group conducted subgroup analyses, including one stratified by \nweight. What was observed was that the stratified efficacy results were comparable and \nconsistent with the overall efficacy results. This can be shared with ACIP committee members. \nDr. Brooks requested the receipt of the data stratified by race and ethnicity. \nDr. Sinha confirmed this is available and will share it with the ACIP committee members. \nDr. Brewer stated for clarity that the primary outcome is medically -attended lower respiratory \ntract infection (MALRI) with one or more indicators of LRI severity, while elsewhere, this is listed \nas a secondary outcome. He also requested clarity on why the LRI hospitalization data looked \n42 \n \n  \n \n \n  \n  \n \n    \n \n \n \n    \n \n \n \n  \n \n \n  \n \n     \n  \n     \n \n \n   \n \n \n \n \n \n  \n \n \n \n  \n \n  \n  \n \n \n \n \n \n  similar. When looking at the all -cause data, there is a significant falloff in efficacy for the primary \noutcome but none for hospitalization data. \nDr. Sinha confirmed that Dr. Brewer's statement was correct. The primary efficacy endpoint was \nMALRI, which required at least one indicator of LRI/Severity with follow -up through five months. \nOne of the secondary endpoints was the same efficacy endpoint but with follow -up through six \nmonths. She also confirmed that efficacy against LRI hospitalization due to any cause is 49%, reflecting the severity of this endpoint; this includes not just RSV determined by the pre-\nspecified endpoint but LRI hospitalization due to any cause. The MALRI endpoint is broad and \nencompasses many diseases in clinics and hospitals. \nDr. Chu followed up on Dr. Jamieson's request. She would like to see the efficacy stratified by \ngestational age and weight. She also requested to see the pharmacokinetic ( PK) data six \nmonths out and whether there will be a faster or slower fall -off with different gestational ages or \nbirth weights. \nDr. Sinha confirmed that these data will be shared with the work group. \nDr. Schec hter asked whether PK or other data indicated the expected durability of protection \nafter the first season and whether primary and secondary event counts tended to occur later or \nsooner after immunization. He also requested data on the durability of protection compared to \nthe timing of the injection and finally inquired whether there was a correlation of protection. \nDr. Sinha clarified that all efficacy points were collected through six months. These data are \navailable. A Kaplan-Mei er curve may be helpful to see that the efficacy is durable through the \nentire six months. Cases were occurring across the entire 180-day period of follow up. There is \nno formal correlate of protection. \nDr. Brewer was surprised by the outcomes and wanted to know whether additional outcomes \ncould have been reported within the presentation. \nDr. Sinha confirmed that all primary, secondary, and tertiary endpoints were reported in the \npresentation. \nDr. Brewer shared a concern about data stability for post hoc analysis. It may be helpful to focus \non either a primary or a primary and secondary outcome. He is concerned about the \nintensiveness of inspecting data across too many outcomes. \nDr. Malini B. DeSilva (Health Partners Institute) presented preliminary data about the RSVpreF \nvaccine, preterm birth, and small for gestational age at birth preliminary results from the Vaccine \nSafety Datalink (VSD). VSD is a collaborative project between CDC and 13 integrated healthcare organizations. It monitors the safety of vaccines used in the U.S., primarily through \nobservational multisite studies of rare and severe events following vaccination. VSD includes \ndata on ~15.5 million individuals across all sites annually, about 3.4% of the U.S. population. VSD reported an annual birth cohort of about 115,000 live births. \nACIP recommended Pfizer’s maternal RSV vaccine with seasonal administration (September to \nJanuary) for all pregnant women 32- 36 weeks gestation in September 2023. In clinical trials, \nPfizer’s maternal RSVpreF clinical trials identified an imbalance in preterm births in the \nvaccinated group compared to the placebo group. Most were late preterm (34– <37 weeks), \noccurred >30 days after vaccination, and occurred in a single country. \n43 \n \n   \n      \n  \n  \n \n   \n  \n \n \n \n \n \n \n \n \n \n  \n    \n \n  \n \n \n \n \n \n   \n   \n \n  \n \n \n \n   \n \n   \n  \n \n \n  \n \n  ACIP judged the benefits of the maternal RSV vaccine ( ABRYSVO ) at 32– 36 weeks’ gestation \nto outweigh the potential risks for preterm birth and the hypertensive disorders of pregnancy. \nThe group evaluated preterm birth (<37 weeks gestation) and small for gestational age (SGA) at birth following maternal RSV vaccination. Most VSD sites started vaccinating in late October or \nNovember 2023. SGA was defined as birthweight below the 10\nth percentile for gestational age \nand sex. In this controlled VSD study, Pfizer’s maternal RSVpreF vaccine was not found to be \nassociated with an increased risk for preterm birth or SGA at birth. Work is in progress on \nanalyzing acute safety outcomes, stillbirth, and hypertensive disorders of pregnancy \n[preeclampsia, eclampsia, and HELLP (Hemolysis, Elevated Liver enzymes and Low Platelets)]. \nDr. Schec hter asked whether the study was limited to a single season or whether there were \nplans for continued surveillance. \nDr. DeSilva confirmed there are plans to continue the study for this season. However, the data \npresented is only for the first season. \nDr. Brewer requested an explanation of how to interpret preterm birth risk by gestation age at \nvaccination from 32 to 36 weeks. \nDr. DeSilva commented that the team does not interpret this to mean that vaccination is \nprotective for preterm birth. The trend is similar in both of the groups.  \nDr. Joseph was reassured that maternal immunization is a safe strategy for protecting infants against RSV. However, the analysis does highlight two points. Overall, the maternal vaccination rate was low, and the licensure data included patients vaccinated earlier than 32 weeks gestation. This is different from the approved dosing window. Given the implementation challenges, she inquired whether the work group plans to look at data from other surveillance systems like the United Kingdom to help inform the risk of preterm birth. \nMs. Moulia stated that she thought that the UK started maternal RSV vaccination in September \n2024 and that the work group c ould review data from the UK when available. \nDr. Asturias requested clarification on the RSV groups, including whether there were any \nexclusions and whether the vaccinated and unvaccinated groups were similar. \nDr. DeSilva shared that vaccinated and unvaccinated people have similar characteristics. \nHowever, there are some imbalances including for race, ethnicity, and age.  \nMs. Danielle Moulia (CDC/NCIRD) reviewed the maternal and pediatric RSV work group’s \ninterpretations and next steps. The policy question being considered is whether clesrovimab \nshould be recommended for all infants <8 months of age entering their first RSV season or born during the RSV season.  Initial efficacy and safety data look promising; however, the work group has requested additional pharmacokinetic, efficacy, and safety data from the manufacturer. The work group also highlighted that clesrovimab had demonstrated a shorter half-life than \nnirsevimab (42 vs. 71 days), the COVID -19 pandemic disrupted the trial enrollment period, and \nclesrovimab and nirsevimab trial outcomes had different definitions. Overall, the work group felt \nthat the initial data merited moving forward with the evidence review for the policy question. \n44 \n \n  \n \n  \n \n \n \n   \n  \n \n \n   \n \n \n \n \n \n \n  \n \n  \n \n  \n \n \n  \n \n    \n \n \n  \n  \n \n \n \n \n  \n \n \n \n  \n   \n  Future evidence to be reviewed by the work group includes additional data on Phase 2b/3 and \nPhase 3 studies, GRADE of evidence, cost-effectiveness analysis, and the EtR framework. It is \nprojected to be presented at the February 2025 meeting, with an ACIP vote possibly as early as \nthe June 2025 meeting, depending on FDA licensure. \nData were summarized on the preliminary findings from the first season of maternal RSV \nvaccine administration in an SD study that found that maternal RSV vaccine during 32– 36 \nweeks’ gestation was not associated with an increased risk of preterm birth or sm all for \ngestational age. The work group felt that messaging about potential risks for hypertensive \ndisorder of pregnancy should be separated from preterm birth. Some work group members felt that when counseling on maternal RSV vaccination at 32– 36 weeks, messaging on potential \nrisks of preterm birth could be softened, or counseling no longer needed to include discussion regarding a possible risk of preterm birth. CDC and FDA will continue to monitor safety data for \nmaternal RSV vaccine, including further VSD analyses for hypertensive disorders of pregnancy. \nDr. Shaw asked whether the preterm birth rates reported in this study were low or within the \nexpected range and if any more was known about the preterm birth signal seen in GSK’s clinical trial. \nDr. DeSilva responded that preterm birth rates in the population and the SGA at birth were in the \nexpected range for the VSD. \nDr. Jones addressed the second question and said there was not a clear biologic explanation. \nDr. Schec hter encouraged committee consideration for language encouraging the speedy \nimplementation of nirsevimab in birth hospitals. \nMs. Moulia noted that the current guidance is that infants born shortly before or during the RSV \nseason should be immunized within one week of birth, ideally during the birth hospitalization. \nCDC is organizing learning collaboratives to share promising practices for nirsevimab \nadministration in birthing hospital s. \nDr. Chatham -Stephens followed up with additional information. CDC is working closely with the \nimmunization programs to enroll more birthing hospitals into the Vaccines for Children Program \nand offering specialized technical assistance to awardees. Some jurisdictions received site \nvisits, focus groups, and key informant interviews. In early August, the CDC held a perinatal and \nmaternal reverse site visit, during which many immunization program managers from across the country also came to discuss these issues. \nMs. Hayes expressed her appreciation for the review of data on vaccinating pregnant women, \nwhich shows that vaccination in this group is safe. \nDr. Brooks moved the meeting to recess and reconvening on October 24, 2024, at 8:00 am\n. \nWith no additional business posed for the day, the ACIP meeting stood in recess until 8:00 AM \non October 24, 2024. \n45 \n \n   \n \n \n \n \n \n    \n \n  \n \n \n  \n \n \n \n \n \n \n \n \n \n \n \n  \n \n \n \n  \n \n  \n \n \n   \n \n \n \n   \n    \n \n  THURSDAY : OCTOBER 24, 2024 \nWELCOME AND INTRODUCTIONS \nCall to Order/Roll Call \nDr. Keipp Talbot (ACIP Chair) c alled to order and presided over the October 24, 2024, Advisory \nCommittee on Immunization Practices (ACIP) meeting. She then conducted a roll call , which \nestablished that a quorum was present. A list of Members, Ex Officios , and Liaison \nRepresentatives is included in the appendixes at the end of this summary document. No COIs \nwere identified for the second day of this meeting. \nAGENCY UPDATES \nCenter\ns for Medicare and Medicaid Services (CMS) \nMs. Mar\ny Beth Hance shared that they have worked hard to amplify CDC and HHS messaging \naround the importance of seasonal and routine immunization. They have talked to state \nMedicaid agencies and interested parties at many touchpoints throughout state connections and \ncommunity involvement. They have appreciated the efforts of representatives from the CDC speaking with state Medicaid agencies to emphasize the importance of immunization and continue to return to the higher pediatric immunization rates seen in previous years. She also highlighted that on September 12, 2024, her colleagues issued a Medicare learning network bulletin that included COVID codes and pricing for this year’s COVID -19 vaccine codes and \npricing for this year’s vaccine. \nCent\ners for Disease Control and Prevention (CDC) \nDr\n. Demetre Daskalakis thanked colleagues at the FDA, industry, and ACIP for an expeditious \nrollout of COVID -19 vaccines. COVID -19, Influenza, and RSV are all available and in the field. \nThere have been interesting changes seen by launching earlier in the year. We have seen a higher uptake of the COVID-19 vaccine during this time of year compared to last year's same date. This is a testament to the close collaborations across the various components of government and industry. The number of respiratory illnesses in the U.S. continues to be low. COVID -19 activity continues to decline in all areas. As expected, there is minimal seasonal flu \nand RSV activity in the southeastern part of the U.S. It tends to start in this area and then sweep across the country. \nHe flagged the number of measles cases seen. As of October 10, 2024, 32 jurisdictions \nreported 267 measles cases. There have been 14 outbreaks reported in 2024, and 70% of \ncases are outbreak -associated. For comparison, four outbreaks were reported during 2023, and \n49% of cases were outbreak -associated. Jurisdictions at the highest risk for measles outbreaks \ncontinue to be those with communities with persistently low MMR vaccination coverage and \nimportations from international locations with measles outbreak s. \nHe also highlighted that respiratory infections caused by Mycoplasma pneumoniae have \nincreased in the United States since last spring among all age groups, particularly young \nchildren. Healthcare providers should consider M. pneumoniae as a cause of pneumonia and \ntest when indicated. Macrolides are the first-line treatment for this infection; some first-line antibiotics used to treat pneumonia, like penicillin, will not treat M. pneumoniae. \n46 \n \n   \n \n \n \n \n \n \n \n \n \n \n  \n   \n  \n \n \n \n \n  \n \n \n \n \n   \n \n \n \n  \n \n  \n \n \n \n \n \n    \n \n \n \n  He shed light on the Vaccines for Children Program for its 30th anniversary. With the \nintervention, 508 million illnesses and 1.29 million deaths in children will be prevented, saving \n2.7 trillion in societal costs. \nFood and Drug Administration (FDA) \nDr. David Kaslow shared that since the last FDA Agency report at the June 2024 ACIP meeting, \nour Vaccines and Related Biological Products Advisory Committee (VRBPAC) convened twice \nand plans to meet again before yearend. The Office of Vaccines Research and Review took \nseveral noteworthy supplemental regulatory actions. \nIn September, VRBPAC met in an open session to discuss considerations related to using \npertussis Controlled Human Infection Models (CHIMs) to demonstrate the efficacy of pertussis \nvaccine candidates for licensure. Two endpoints were discussed: mild disease such as cough, \nand colonization. Considerations on using these models included their relevance to pediatric \npopulations, their limitations with real -world pertussis infection and disease, and the ability to \nassess the long-term effectiveness of pertussis vaccine candidates. \nIn October, VRBPAC also convened in an open session to make recommendations on influenza \nvaccine strains for the 2025 influenza season in the Southern Hemisphere and discuss pandemic preparedness for highly pathogenic avian influenza virus, including considerations for vaccine composition for (H5) vaccines. The FDA proposed an Inter -Pandemic Period Strain \nChange Process to use the inter -pandemic period to accrue additional safety and \nimmunogenicity evidence with updated prototype vaccines and potentially save critical \npandemic response time to have updated vaccines when needed. \nFDA also anticipates a VRBPAC meeting on December 12th to discuss considerations for RSV \nvaccine safety in pediatric populations. \nOn 19 August, the meningococcal B vaccine, BEXSERO, with a dosing schedule in individuals \n10- to 25 years of age of two doses administered at 0 and ≥1 month under accelerated approval \nwas revised to two doses administered at 0 and 6 months, and to include a three-dose schedule \nof BEXSERO administered at 0, 1-2, and 6 months for the same age group, now under \ntraditional approval. \nOn 29 August, Smallpox and Mpox (Vaccinia) Vaccine, Live, ACAM2000\n®, was approved to \ninclude mpox disease prevention in individuals at high risk for mpox infection. It was approved \nwith an updated medication guide. \nFinally, on Tuesday this week, the RSV vaccine ABRYSVO was approved to prevent lower \nrespiratory tract disease caused by RSV in individuals 18-59 years of age who are at increased \nrisk for lower respiratory tract disease caused by RSV. \n47 \n \n  \n \n    \n  \n  \n \n  \n \n   \n \n \n  \n \n    \n \n \n   \n \n  \n \n \n \n   \n \n  \n   \n    \n  \n   \n   \n \n \n  \n \n  Health Resources and Services Administration (HRSA) \nCDR Paul McClung shared that t he Division of Injury Compensation Programs (DICP ) continues \nto support the Nation’s public health through the administration of the National Vaccine Injury \nCompensation Program (VICP ) and the Countermeasures Injury Compensation Program \n(CICP ). As a part of this support, HRSA, in partnership with the Centers for Disease Control and \nPrevention (CDC), sponsored a study from the National Academy of Sciences, Engineering, and Medicine (NASEM) to review the evidence from 19 potential harms of COVID -19 vaccines and \nnine (9) potential shoulder injuries from intramuscular administration of vaccines more broadly. The NASEM committee drew 65 conclusions where it could not find evidence to establish, accept, or reject a causal relationship and drew 20 conclusions with sufficient evidence, with the final release of the report in August 2024. The important conclusions drawn by the committee will support decision-making for VICP and CICP when adjudicating compensation claims.   \nIn support of VICP, the Advisory Commission on Childhood Vaccines (ACCV ) was briefed on \nthe NASEM report on July 11, 2024. ACCV made motions to establish a workgroup to amend \nthe Vaccine Injury Table’s Qualifications and Aids to Interpretation (QAI) to address conclusions and information provided by NASEM on shoulder injuries. They also added an agenda item to \nthe next ACCV meeting, with input from HRSA/HHS, about potential research areas of interest regarding shoulder injuries. \nACCV currently has several vacancies and is seeking nominations. Additional information is \navailable on the ACCV website. If you have questions or want to submit a nomination, please \nvisit our website or email ACCV@hrsa.gov . \nVICP is a no-fault alternative to the traditional legal system for resolving vaccine injury petitions. \nIt was created in the 1980s after lawsuits against vaccine companies and healthcare providers \nthreatened to cause vaccine shortages and reduce U.S. vaccination rates. VICP continues to serve as a keystone program in the Nation’s ability to stabilize vaccine supply and protect the \nNation’s public health by expeditiously processing claims. \nOver the past two fiscal years, VICP has made substantial strides in reducing the backlog of \nclaims awaiting review by an HRSA provider.  From October 2022 to October 1, 2024, VICP has \nreduced the number of claims activated by the U.S. Court of Federal Claims from 1,107 to \n166. Over this same period, the waiting times for a HRSA medical review have decreased from \nmore than 12 months to 49 days.  In FY2024, VICP received 1,161 petitions, adjudicating 1,374 \nclaims and awarding over $149 million to petitioners and over $53 million for attorney’s fees and \ncosts. \nCICP is also a no-fault compensation program. CICP adjudicates requests for benefits alleging \nan injury from covered medical countermeasures deployed in response to a pandemic, \nepidemic, or security threat covered under a Public Readiness and Emergency Preparedness Act declaration by the Secretary of Health and Human Services. As of October 1, 2024, 13,468 \nclaims alleging injuries/deaths from COVID-19 countermeasures had been filed with the CICP.  CICP continues to make substantial progress in processing claims and has now rendered \ndecisions on 3,318 COVID-19 claims. \n48 \n \n    \n  \n  \n   \n \n \n  \n \n \n \n \n \n \n   \n \n \n \n \n \n \n \n \n \n \n \n \n  \n \n \n \n   \n   \n \n \n \n \n \n In August 2024, the Bureau of Primary Health Care (BPHC) released its Uniform Data System \n(UDS) data. The UDS captures the immunization rates for children two years of age and under \nbased on the CDC10 series. BPHC is actively collaborating with CDC to promote immunization \nefforts across the spectrum by promoting various tools and resources that CDC has developed \nthrough different communication channels. \nHRSA’s HIV/AIDS Bureau also continues its important work through the Ryan White HIV/AIDS \nProgram, which continues to support access to mpox vaccination. \nIndian Health Services (IHS ) \nDr. Matthew Clark shared that the Indian Health Service remains committed to immunization as our leading clinical and public health prevention priority. As part of our ongoing national E3 \nvaccine strategy, IHS offers every ACIP -recommended vaccine when appropriate to every \npatient at every encounter. HIS has designated 32 E3 pilot sites in 9 IHS Areas, including \nfederal, tribal, and urban Indian organization teams. \nThe IHS E3 Vaccine Strategy continues to bear fruit as pilot sites innovate at the local level and \nshare best practices regarding effective immunization strategies in tribal communities to cross -\npollinate our system of care. This year, five IHS E3 Champions have been designated in the \nAlaska, Bemidji, Great Plains, Nashville, and Oklahoma City Areas. Each has demonstrated \nexcellence by exceeding established thresholds to improve vaccine coverage rates for AI/AN people. \nOver the last several months, we have been developing E3 training materials for an academic \ndetailing activity. This week, six healthcare professionals representing federal, tribal, and urban \nIndian organization programs are undertaking intensive training to become E3 ambassadors in \ntheir respective a reas. Following completion of training, they will undertake outreach to educate \nand support immunization staff working in tribal communities in implementing the IHS E3 \nVaccine Strategy. \nFollowing ACIP action in June of this year related to a preferential recommendation for the \nhexavalent vaccine VAXELIS\n® in AI/AN infants , through a variety of platforms including written \nguidance and both in-person and virtual events, IHS has been working diligently to communicate this option to vaccination teams serving tribal communities. We plan to monitor \nthe impact of this recommendation on vaccine coverage rates and potential ly disease \noutcomes. \nFinally, IHS is actively engaged in its annual seasonal vaccination campaign to reduce the risks \nof vaccine-preventable respiratory viral diseases in Indian Countr y, including influenza, COVID, \nand RSV. This includes aggressive efforts to promote access to and uptake of both maternal \nRSV vaccine and nirsevimab among AI/AN infants and young children. Like last year, in addition to collaboration with the Vaccines for Children program, IHS procured and distributed a supplemental supply of nirsevimab to support programs, especially those in remote locations, \nwith planned early -season vaccination activities. This year, IHS has also worked closely with \nfederal partners at the CDC and the Administration for Children and Families (ACF) to develop \nmaterials and provide education to support home-based outreach to Indigenous families about \nthe importance of recommended RSV immunizations. \n49 \n \n  \n \n \n \n \n \n \n \n \n \n \n  \n \n \n \n  \n \n  \n \n  \n  \n \n \n \n \n     \n   \n   \n \n \n   \n \n \n   \n \n \n \n \n  Working in collaboration with our federal, Tribal, and Urban Indian organization partners, the \nIndian Health Service will continue our efforts to mitigate the risk of vaccine-preventable illness \nin Indian Country. \nOffice of Infectious Disease and HIV/AIDs Policy (OIDP) \nDr. Chinedu Okeke shared that t he National Vaccine Advisory Committee (NVAC) met on \nSeptember 12-13, 2024. At this meeting, the committee showcased work that can help to \nstrengthen the U.S. vaccine and immunization system and inform vaccine policy. The meeting \nbegan with a panel presentation on implementing the ACIP universal vaccine recommendation for adults aged 19- to 59 years of age and adults aged 60 years of age and older with known \nrisk factors for hepatitis B. The committee also heard presentations on provider payment and RSV immunization across lifespan. \nMuch of the discussion at this meeting also focused on innovation to provide additional context \nfor the report the committee is currently working on. NVAC hosted speakers on tuberculosis vaccine innovation and some challenges of advancing the tuberculosis vaccine pipeline. It also \nhosted a panel on new research to inform future HIV vaccine development. \nOn the first day of the meeting, we learned more about a new HHS campaign called Risk Less. \nDo More. NVAC also hosted two panels focused on immunization equity. The first panel \nshowcased two innovative projects, and the second panel explored lessons and evaluation \napproaches. To fulfill the charge of providing input to advance the development of the Vaccine National \nStrategy , the committee participated in two working sessions to discuss potential \nrecommendations for new goals, indicators, and objectives. \nIn collaboration with the HHS Interagency Vaccine Work Group, OI DP has started planning, \ndata gathering, and engagement efforts for the next iteration of the National Vaccine Strategic \nPlan for 2026-2030. OIDP has posted the Request for Information for the public on the Federal \nRegister, and the 60-day countdown has begun. Everyone is encouraged to provide feedback \non all the strategies. We encourage ACIP members to actively submit feedback and \nrecommendations during this process . \nOIDP is putting together several virtual and in-person sessions. The first listening session will \noccur on October 29 from 2 to 3:30 PM ET. The second opportunity is a vaccine strategy -\nfocused listening session on October 31 from 1 to 2:30 ET. In November, OIDP will host two \ngeneral sessions for all the National Strategic Plans on November 13 and November 14 \n(Spanish language) from 2 to 3:30 ET. \nOIDP continues to lead the \"Summer of Pride\" Mpox Equity Initiative, a nationwide effort to increase access to mpox vaccines for communities most at risk. This initiative leverages Pride festivals and other events to reach these communities effectively . \n50 \n \n  \n    \n  \n \n \n \n  \n \n \n \n \n \n   \n \n  \n \n  \n \n \n \n \n \n   \n  \n  \n \n   \n  \n \n  \n \n  \n  \n \n \n \n  \n \n \n  \n \n  \n  On September 4th, OIDP and the HHS Office of Intergovernmental Affairs organized a virtual \nstakeholder call for community partners. This call served as a continuation of OIDP's previous \ndiscussions this year with community partners and health department staff involved in the mpox response. The stakeholder call, led by Assistant Secretary for Health ADM Rachel Levine and \nCDC Director of the National Center for Immunization and Respiratory Diseases Demetre Daskalakis, provided an update on the Clade 1 mpox virus and the U.S. preparedness and response. OIDP is currently planning another stakeholder call for November. \nNational Institute of Health (NIH) \nDr. John Beigel shared that NIAID is sponsoring a Phase 1 trial testing the safety of an \nexperimental nasal vaccine for SARS -CoV -2. The vaccine utilizes a new virus vector, murine \npneumonia virus, related to human RSV. Scientists at the NIH/NIAID Laboratory of Infectious \nDiseases designed and tested it in pre-clinical studies. This is part of Project NextGen, a \nprogram in both BARDA and NIAID that aims to accelerate the development of next generati on \nCOVID -19 vaccines . \nFor m pox, NIAID sponsored a clinical trial of the MVA- BN mpox vaccine in adolescents, \ndemonstrating that it is safe and generated an antibody response equivalent to that seen in adults. Adolescents are among the population groups affected by mpox in the current outbreak in the DRC. Bavarian Nordic received EMA approval to extend the MVA -BN authorization to \ninclude adolescents. \nAs part of the U.S. government’s response to the current mpox outbreak, NIAID has updated its \npriorities for mpox research. The NIAID mpox research agenda includes objectives to respond \nto the mpox outbreak including trials to evaluate ways to stretch the vaccine supply, and to \ndevelop novel vaccines and therapeutics.  \nFor m alaria, two NIH -supported trials of a novel malaria vaccine in healthy adults in Mali found \nthat all regimens were safe and generated a robust immune response. The vaccine candidates \nconferred a significant degree of protection from parasite infection and clinical malaria that was sustained over two years without the need for a ny booster dosing.  \nFor RSV, NIAID is conducting a randomized, open-label Phase 4 s tudy of maternal RSV \nvaccination compared to infant n irsevimab or both products combined. The trial opened to \nenrollment in September 2024 and evaluates antibody titers for one year, which is expected to \ninform clinical use of these products. \nNIAID has named Sarah W. Read, M D, MHS, as the Principal Deputy Director for the institute \nfollowing Dr. Hugh Auchincloss’s retirement in September 2024. \nNIH has established the Research and Development of Vaccines and Monoclonal Antibodies for \nPandemic Preparedness network —called ReVAMPP — to focus on “prototype pathogens” to \ndevelop vaccine candidates and monoclonal antibodies to better protect against emerging \npathogens . By studying specific prototype pathogens, scientists will build a knowledge base that \ncould be applied to future emerging viruses. \n51 \n \n  \n \n   \n   \n     \n \n  \n   \n \n   \n \n  \n   \n \n  \n  \n \n \n \n  \n   \n  \n   \n  \n \n \n \n   \n  \n  \n \n      \n   \n \n \n  MENINGOCOCCAL VACCINES \nDr. Jamie Loehr, chair of the ACIP Meningococcal Vaccines Work Group, introduced the \nmeningococcal vaccines session. The work group is working on three main topics. The work group is reviewing GSK ’s pentavalent MenABCWY vaccine, with a regulatory decision expected \nby February 14, 2025, and anticipating a vote on this topic in February 2025. The work group \nalso has discussed the newly approved interval and dosing change for MenB -4C ( BEXSERO), \nwith a vote planned for this meeting. The work group also is continuing its review of the \nadolescent meningococcal vaccine schedule and expects a vote in 2025. \nFrom 1996- 2023, meningococcal disease cases dropped by 90%. There are 0.13 cases per \n100,000 population (1 in a million cases). This drop is primarily attributed to serotypes B, C, and Y. There was an increase in cased due to serogroup Y in 2023. During 2012-2021, many of the \ncases were seen in the elderly and age group <1 year, but current policy discussions are focused on the age groups 11-15, 16-20, and 21-25 years of age. \nDr. Xiaoyu Dong (CDC/NCIRD) presented the results of the economic analyses of GSK (MenABCWY) vaccine among adolescents in the U.S. The goal for the economic analysis was \nto evaluate the effectiveness of vaccinating adolescents with the GSK pentavalent vaccine (MenABCWY) compared to the current recommendation of the MenACWY/MenB vaccine. The current recommendation is MenACWY vaccine (Q): 1st dose at 11– 12 years; 2nd dose at 16 \nyears. In addition, ACIP recommends MenB vaccine (B): 1st and 2nd dose at 16– 23 years \n(preferred 16– 18 years), based on shared clinical decision- making. \nThree policy questions (PICO s) are under consideration. \n1. PICO 1: Should the pentavalent vaccine (P, MenABCWY) be included as an option for \nMenACWY/MenB vaccination in people currently recommended to receive both vaccines \nat the same visit? (Q -P-B) \n2. PICO 2: Should the pentavalent vaccine be included as an option for people currently \nrecommended to receive MenACWY only? (P -P) \n3. PICO 3: Should the pentavalent vaccine be included as an option for people currently \nrecommended to receive MenB only? (Q -P-P) \nThe intervention was the use of pentavalent in adolescents compared to current \nrecommendations or related strategies. For reference, each strategy was compared to no \nvaccination. The economic model included the entire cohort of current 11-year -olds in the U.S. \nVaccination costs and meningococcal cases were assessed for 19 years. Costs and health outcomes of meningococcal cases were evaluated from age 11 years through the participant’s \nentire lifetime. The analysis was from the societal perspective and a 3% discount rate was \napplied. \nInvasive meningococcal disease (IMD) rates among unvaccinated individuals were based on \nobserved rates from 2003-2005 for serogroups ACWY and from 2012-2014 for serogroup B. \nCase fatality rates were estimated at 15.4% for serogroups ACWY and 9.4% for serogroup B. \nSome of the sequelae of IMD include hearing loss, skin scarring, neurologic disability, and \nsingle and multiple amputations. Vaccine efficacy was estimated at 79% for the first Q dose and 99% for the subsequent doses and 64% for the first dose of B and 79% for the second, with \nwaning over time for all doses. In PICO 1, the intervention P is introduced as an alternative to QB. In PICO 2, P doses were introduced to replace current Q doses. \n52 \n \n    \n  \n \n \n  \n \n  \n \n  \n   \n  \n   \n  \n  \n  \n    \n  \n \n  \n \n   \n  \n \n \n  \n \n \n \n \n \n \n \n \n  \n  \n   \n  In PICO 3, P replaced the B dose. The vaccine cost per dose (including administration) $177 for \nQ, $224 for B, and $245 for P.  \nThe model estimated that without vaccination, there would be an estimated 233 IMD cases and \n33 deaths. The two vaccination strategies in PICO 1 yielded identical outcomes, with 142 IMD \ncases and 19 deaths. In PICO 2, the main difference between the compared strategies was the \nprotection that P doses offer against serogroup B, which prevented an additional 12 IMD cases and one death. In PICO 3, the difference in health outcomes comes from the last dose in each strategy. The final dose of P in the Q -P-P will prevent one additional IMD case compared to \nusing B as the last dose. Both Q-P-B and Q -P-P were cost -saving compared to Q -QB-B. \nHowever, compared to no vaccination, the cost per QALY gained was high for all vaccination \nstrategies (>$2M per QALY). \nDr. Dong provided a summary comparison of GSK’s model to the CDC model.  GSK’s model used a higher incidence and coverage rate than was used in CDC’s. The initial VE for 1\nst dose \nMenB was 64% in the CDC model compared to 33.5% in GSK’s model. In CDC’s model, VE \ndeclined to 0% in 5-10 years compared to 0% after more than 20 years in GSK’s model. CDC’s model included five sequelae outcomes with an aggregate probability of 22%, while GSK’s \nmodel included 16 sequelae outcomes with an aggregate probability of 55%. Both models \nshowed cost -saving for PICO 1. The GSK model showed a higher ICER than CDC’s models for \nPICO 2. Both models showed cost-saving in PICO 3 when the intervention was compared to Q -\nQB-B. \nThe study had limited VE data, assumptions on the third dose effectiveness of MenACWY, unknown pre-vaccination incidence rates, and estimated costs for GSK’s pentavalent vaccine. The study also did not account for additional protection against gonorrhea, the potential \nincrease in vaccine uptake, or benefits from fewer adverse events from reduced injections. The \nCDC model used vaccine coverage data based on the current shared clinical decision-making \npractices and did not model any changes to the routine use of MenB vaccines. \nDr. Dong summarized that Q -P-B was cost -saving relative to the current recommendation (vs. \nQ-QB -B). P- P could improve health outcomes but costs $11.3 million per QALY saved (vs. Q -Q). \nQ-P-P could improve health outcomes, but estimated economic value varied depending on the \ncomparator. Q -P-P is cost -saving compared to Q -QB-B, but compared to Q-P-B, it costs $4.5 \nmillion per QALY gained. \nDr. Maldonado was surprised that the work group would choose to give a vaccine at three \ndifferent times rather than a pentavalent vaccine, which we would only have to give twice, \nespecially in a population like adolescents, who are very hard to bring back. She was curious \nhow retaining an adolescent three different times would not impact efficacy. She questioned how 2 doses of a broader vaccine (i.e., pentavalent vaccine) would be least cost-effective and whether the vaccine cost drives this decrease. She also inquired whether P -P can be compared \nto Q-QB-B. \nDr. Dong clarified that Dr. Maldonado is speaking on PICO2, in which P -P is compared to Q -Q. \nWithin this comparison, the travel trips would be the same: one trip for the first dose and another \nfor the second. When the incremental cost-effectiveness ratio is calculated, the advantage of \nhaving fewer trips would be canceled. The study is limited when comparing P -P trips to other \nstrategies. She also clarified that P-P was not compared to Q -QB-B because it was not one of \nthe PICO questions, but there would be a reduced trip in this comparison. \nDr. Leidner stated that if there is an additional request to compare P-P to Q -QB-B, the \neconomics team would gladly do so. \n53 \n \n  \n \n       \n  \n  \n \n  \n \n   \n \n   \n   \n \n \n  \n \n \n   \n   \n \n \n    \n  \n \n   \n  \n \n \n   \n  \n   \n  \n \n Dr. Schechter questioned whether the comparison of Q-P-P vs. Q -QB-B in PICO 3 would be \ncomparable with other pentavalent formulations already available. \nDr. Dong shared that PICO 1 is cost -saving because the net health outcome is the same. \nOverall, cost -saving occurs because P is less than the cost of QB. In Q -P-P vs. Q -QB-B, Q -P-P \nis cost -saving because the last dose of P protects against serogroup ACWY. The difference \nbetween P and QB makes the price lower. Dr. Leidner added that if Dr. Schechter was referring to the pentavalent vaccine that is already in \nuse, the results from this analysis, which was done presented June 2023, were similar, and it \nwas also cost -saving. \nDr. Schechter inquired if the baseline risk was lower than before the availability of vaccines and \nwhether this would be associated with increased cost estimates. He also asked about the vaccine coverage inputs in the model ; for the Q -P-B model, was their overlap between the \n27.3% receiving Q and the 32.4% receiving P?  He also asked what impact a coverage lower \nthan 59% would have on cost-effectiveness. \nDr. Leidner confirmed that if the disease risk is lower, the disease burden would be lower, and \nthere would be less disease to prevent with the use of vaccines. Therefore, the cost-\neffectiveness ratios could increase. In this scenario, if a person was using shared clinical \ndecision-making after they got their second Q, they went on to get their B series. Those who did \nnot choose to get the B vaccine still got the Q vaccine to finish their Q series. He also stated that a lower coverage simulation was not run, but this is also something the team could investigate in the future. \nDr. Shaw requested confirmation that the P-P intervention would prevent the need for a second \nB vaccine. In this case, comparing P -P to Q -QB-B would be relevant. \nDr. Dong responded that this simulation was not included in the model, and Dr. Leidner added that it would be brought back to the team to develop this comparison. \nDr. Loehr requested that the committee consider that we are only looking at hundreds of cases \nvs other diseases that result in thousands of cases. Regarding the cost analysis, PICO 1 is cost -\nsaving because the manufacturer has priced it so that MenACWY might be $180 and Men B \nwould be $180, but combined, they are only $220. The pentavalent vaccine is much less \nexpensive than the two vaccines combined, resulting cost-saving compared to separate \nadministration. He reminded the group that the ACIP has decided on shared clinical decision-\nmaking for MenB vaccine at the current time, so many people get Q -Q without B -B. He \nemphasized that the ICER is in millions, not thousands , of dollars per QALY . Many other ACIP-\nlike o rganizations will not consider ICERs over $100,000 to $150,000 per QALY gained. He \nwants the group to know that we are contemplating spending a lot of money on very few cases. He recognizes this is a dramatic, devasting disease for those who get it but would like to \nconsider fiscal prudence. He suggest ed that the manufacturers heed the concern that vaccine \nprices are becoming too expensive for him as an ACIP member to contemplate. \nMs. Moser added that cost is only one part of the work group's consideration. This disease kills \n1 to 2 of 10 people that it infects and permanently disables half of those who survive; the \ncommittee has to take into account the costs beyond the economic costs. The models are \nsensitive to changes in inputs and so there is uncertainty about what will actually happen, if a recommendation is made.  She also shared that there are a variety of points of view within the committee. \n54 \n \n  \n  \n  \n \n    \n  \n \n \n  \n \n   \n   \n \n \n \n   \n   \n \n  \n \n  \n \n  \n \n \n  \n  \n  \n \n \n \n \n \n   \n \n  \n    \n    Dr. Middleman called for action regarding pharmaceutical companies' high vaccine costs. She \nalso added that the vaccine recommendation is confusing and should be simpler and more \nconcise. \nDr. Sarah Schillie (CDC/NCIRD) discussed the Evidence to Recommendations Framework \n(EtR), which includes GRADE for the GSK Pentavalent (MenABCWY) vaccine. As a review, the \ncurrent routine schedule includes one MenACWY dose at age 11-12 years and a booster at 16 years. Two MenB doses at age 16-23 years (shared clinical decision-making [SCDM]). The \nMenACWY vaccine is also recommended for persons at increased risk, including some \nmicrobiologists, those exposed during an outbreak, those traveling to hyperendemic areas, first -\nyear college students (if not already vaccinated), and those with some health conditions such as asplenia, complement deficiency , complement inhibitor use, or HIV infection. MenB is also \nrecommended for persons at increased risk, including some microbiologists, those exposed during an outbreak, and those with some medical conditions, including asplenia, complement deficiency, and complement inhibitor use. MenACWY vaccines are interchangeable, but MenB vaccines are not. \nThere are two new MenABCWY vaccines. Pfizer manufactured Penbraya, which ACIP voted on \nin October 2023. GSK manufactures the other and is anticipating an ACIP vote in February \n2025. Each vaccine is a combination of an existing MenACWY and an existing MenB vaccines. \nBoth vaccines are intended to be administered as two doses separated by six months and \nindicated for persons 10- 25 years of age. The ACWY component in the Pfizer vaccine is \nNimenrix, while in the GSK, the component is Menveo. The B component in the Pfizer vaccine is TRUMENBA\n®, and BEXSERO in the GSK. \nThe policy questions for GSK’s pentavalent vaccine mirror those previously used for the Pfizer \nvaccine and are as follows: \n• Should the GSK pentavalent vaccine be included as an option for MenACWY/MenB \nvaccination in people currently recommended to receive both vaccines at the same visit? \n• Should the GSK pentavalent vaccine be included as an option for people currently \nrecommended to receive MenACWY only? \n• Should the GSK pentavalent vaccine be included as an option for people currently recommended to receive MenB only? \nThe critical outcomes included meningococcal disease caused by serogroups A, B, C, W, and Y, \nshort-term immunity, and serious adverse events. PICO 1 translates to the schedule option Q -P-\nB, PICO 2 to the schedule option P -P-B, and PICO 3 to the schedule option Q -P-P. \nDr. Schillie began the discussion of the EtR domains with the public health problem. Invasive \nmeningococcal disease (IMD), which often presents as meningitis or bacteremia, progresses \nrapidly. It affects previously healthy young people, and 10-15% of cases are fatal even with \nantibiotic therapy. About 20% of survivors experience long-term sequelae. The work group felt \nthat IMD is an important public health problem for all three PICOs. \nSeven trials were included for evidence review for benefits and harms. Included studies were \nrandomized trials; all except one were blind to the observer. Four studies contributed to assessing short-term immunity one month after one MenACWY vaccine dose in healthy persons. The seroresponse risk ratio ranged from 0.94 to 1.03 for serogroups A , C, W, and Y. \nThe certainty was deemed moderate. For persons at increased risk, the certainty estimate was further downgraded for indirectness and the certainty was low. The certainty of evidence for \nshort-term immunity after series completion was similar to that found following one dose. \n55 \n \n  \n   \n  \n \n  \n \n   \n  \n  \n  \n \n \n   \n  \n \n  \n  \n   \n \n    \n \n \n  \n \n     \n  \n \n    \n   \n    \n  \n \n  \n  \n \n \n  \n  No studies informed long-term immunity for the MenACWY vaccine. One study informed long-\nterm immunity assessed at two years for MenB vaccine . The overall certainty level was low for \nhealthy people and very low for people at increased risk. \nSeven studies informed adverse events. Serious adverse events related to vaccination occurred \namong three subjects who received the pentavalent vaccine compared to one who received the \nMenACWY vaccine and two who received the MenB vaccine. The certainty was rated moderate for healthy people and low for people at increased risk. For non-serious adverse events for healthy people, the certainty level ranged from moderate to high, with low to moderate certainty levels for people at increased risk. \nIn summary, for PICO 1, evidence for meningococcal disease caused by serogroups A, B, C, W, \nand Y and interference with other vaccines administered concurrently is lacking. Evidence for \nshort-term immunity for ACWY and B serogroups is moderate and low for healthy persons and \npersons at increased risk, respectively. Evidence for serious adverse events is moderate and low for healthy people and people at increased risk, respectively. Similarly, evidence for nonserious adverse events is moderate and low for healthy people and people at increased risk, respectively. Evidence for persistent immunity is only available for MenB serogroups and is low and very low for healthy persons and persons at increased risk, respectively. The summary is \nsimilar for PICO 2 and 3, but the evidence lacks informing persistent immunity for MenACWY \nserogroups , affecting PICO 2. \nThe work group felt that the desirable anticipated effects are small for all three PICOs. The \nundesirable anticipated effects are minimal for PICOs 1 and 3 and small for PICO2. For PICO 1, \nthe work group felt the intervention was favored but varied for PICO 2 and 3. The overall \ncertainty of evidence for short-term immunity was moderate or low for the three questions , and \nthe overall certainty of evidence for serious adverse events was moderate or low for the three \nquestions. \nFor the values domain, in 2023 about 85% of 13-year -olds received at least one MenACWY \nvaccine dose, and approximately 60% of 17-year -olds had at least two doses , and about 32% \nand 13% of 17-year -olds received at least one or two doses of MenB vaccine, respectively.   \nAdditionally, almost 90% of 16- to 23 -year-olds and 69% of their parents indicated they would \nprefer a simplified vaccine schedule, with fewer injections and fewer visits . The work group felt \nthat the target population would feel that the desirable effects were large relative to the \nundesirable effects for PICO 1, were probably large for PICO 2, and were large or probably \nlarge for PICO 3. This is similar to the work group’s rating for the Pfizer pentavalent vaccine. \nThe work group felt that there was probably not or was not important uncertainty or variability in \nhow much people value the primary outcome for PICO 1. There was more uncertainty for PICO \n2 and 3, similar to the ratings for the Pfizer pentavalent vaccine. \nFor acceptability, the CDC’s General Best Practice Guidance for Immunization and the American Academy of Pediatrics Red Book both state a general preference for combination \nvaccines over separate injections of equivalent component vaccines. Adolescents prefer fewer \ninjections due to injection site discomfort, and parents/caregivers prefer fewer injections to reduce the number of physician visits. The work group felt that the intervention is or probably is acceptable to key stakeholders with more confidence and acceptability for PICO 1. \nFor the resource use domain, Q -P-B was cost -saving relative to the current recommendation \n(vs. Q -Q-B- B). P-P-N could improve health outcomes but costs $11.3 million per QALY saved \n(vs. Q -Q-N). Q-P-P is cost -saving compared to Q -Q-B-B. Q -P-P is $4.5 million per QALY saved \nmore than Q -P-B. The work group felt PICO 1 would efficiently allocate resources, but this \nvaried for PICO 2 and 3. \n56 \n \n  \n \n \n \n   \n \n   \n \n  \n  \n  \n   \n  \n \n \n \n   \n \n \n  \n  \n    \n    \n \n  \n \n   \n  \n \n \n  \n \n \n \n \n  \n \n \n \n \n \n For equity, an increase in IMD has been observed among Black or African American individuals. \nAmong 11- to 20-year -olds, case counts were too small to examine by year, but the average \nannual incidence across 2015-2023 was highest among Black or African American individuals. IMD data by ethnicity showed a higher incidence among Hispanics starting in 2019. Among 1 1-\nto 20-year -olds , the average yearly IMD rate was higher among those who were not Hispanic or \nLatino. Counties with lower socioeconomic status (SES) had fewer MenB doses stocked \ncompared to higher SES counties . The provider ’s or patient's awareness of an SCDM \nrecommendation is a prerequisite for patient discussions and could lead to health inequities. \nThe pentavalent vaccine could potentially reduce disparities among those interested in MenB \nvaccination but not receive clinical care, including a discussion of the MenB vaccine. The lack of MenB vaccine interchangeability currently restricts existing MenABCWY vaccine use to patients and providers stocking Pfizer MenB vaccine products. The work group felt that health equity would probably be increased or be increased with the GSK pentavalent vaccine. This is different \nfrom responses previously noted for the Pfizer vaccine. \nDr. Schillie shared that challenges with insurance or financial burdens related to the pentavalent \nvaccine are not expected for the feasibility domain. GSK pentavalent vaccine would provide an additional option and may reduce the number of doses for some people. The lack of MenB \nvaccine interchangeability complicates stocking considerations. Overall, the work group felt the \nintervention would be feasible to implement. \nIn summary, the determinations are generally favorable for PICO 1 and somewhat less \nfavorable for PICO 2 and 3. For PICO 1, the work g roup felt that the desirable consequences \noutweighed the undesirable ones . For PICO 2 and 3, the work group was divided. They did feel \nthat there was sufficient information to move forward with the recommendation. The work group \ndoes recommend the intervention for PICO 1. It does not recommend the intervention for PICO 2 and was evenly divided in recommending PICO 3. Several Work Group members noted that it \nwould be important to harmonize recommendations between the GSK and Pfizer pentavalent \nvaccines unless there is a vaccine-specific reason for having a different recommendation. An \ninterim recommendation for the GSK vaccine could mirror the recommendation made for the \nPfizer vaccine last year. Recommendations for use of both pentavalent vaccines could then be revisited as part of future adolescent schedule deliberations . \nDr. Loehr invited the ACIP members' comments on PICO 3 since the work group differed in opinion on that option but may favor it. He stated that accepting this would cause a lack of \nharmony between the two pentavalent vaccines. He does not feel it is acceptable because it \nwould not be harmonized among the vaccines. \nDr. Chu agreed that harmonizing is essential. She felt the most logical thing would be to accept \nPICO 1 and then wait for subsequent data showing whether the P -P strategy is comparable to a \nthree-dose strategy. \nDr. Shaw requested confirmation that the P-P-B vs the current recommendation has not been \nmodeled.  \nDr. Schillie stated that the work group is considering revisions to the adolescent schedule in the \ncoming months but would first like to address the use of the GSK pentavalent vaccine. \nCurrently, the work group only considers the pentavalent vaccine in the context of different options for existing recommendations.  \n57 \n \n  \n \n \n \n \n   \n \n \n \n \n  \n \n \n \n  \n \n \n  \n \n \n  \n  \n \n \n \n \n \n  \n \n \n \n \n Dr. Asturias emphasized that before integrating any pentavalent vaccine into the immunization \nschedule, we should transition from using a combination of vaccines with both a recommended \nschedule and a shared clinical decision-making schedule to including the MenB vaccine as part \nof the recommended schedule. I f MenB is to be added, it should be fully endorsed as a \nrecommendation rather than leaving it as a shared decision option, which could create confusion among parents and providers. This approach raises the question of whether we should prefer a three-dose series or maintain a two-dose regimen. Dr. Asturias expressed his concern about any changes that might diminish the first recommendation, which he noted that \nparents have consistently valued. \nDr. Loehr clarified that the Q -P-B schedule (PICO 1), which the work group is considering \nrecommending, is still a shared clinical decision-making. The P and B are only offered if, after \nshared clinical decision- making, the family or the child decides that they want B. \nDr. Maldonado, as a pediatrician, expressed concerns regarding the complexities of shared clinical decision-making, particularly for primary care providers dealing with devastating diseases with low incidence rates. She highlighted the challenges faced by providers in addressing this issue, especially considering the notably low uptake of the MenB vaccine \nattributed to shared clinical decision- making. Dr. Maldonado suggested the importance of \nstreamlining recommendations to align them with the routine vacci nation schedule, advocating \nfor a swift transition into a non-shared clinical decision-making approach to enhance vaccination \nuptake and ensure patients receive timely and effective care. \nMs. Moser clarified that the Pfizer vaccine is already approved for what we show at PICO 1. The \nimpending schedule review made this discussion very complex for the work group. It was \ndetermined that it was best to address the GSK vaccine in comparison to the Pfizer vaccine . \nThe work group will revisit this when we return to looking at the routine schedule. \nDr. Brooks addressed Dr. Loehr's point regarding the importance of focusing on ICERs that \namount to millions of dollars. He noted that issues would likely arise if we do not achieve \nharmonization, and therefore, he would not support going out of harmony. He expressed his preference for PICO 1. If the family wishes to pursue option B, it would be a cost-saving choice. Seeing the absolute numbers in some of the outcome data would be beneficial since they are \nvery, very low. \nDr. Ch en agreed with the need to harmonize to reduce complexity. She also requested \nconfirmation that the two pentavalent vaccines are not interchangeable because they contain different MenB components. If so, it would be difficult for clinics to stock all three vaccines. She raised the issue of the duration of immunity for MenACWY. \nDr. Schillie confirmed that Dr. Che n’s assumption was correct. \nDr. Talbot noted that while the QPB may appear simple, the reality is more complex. When \nstocking three vaccines with \"Meningitis \" on their labels, there is a significant risk of \nadministering the wrong vaccine. This is an important consideration. She pointed out that when the conjugate pneumococcal vaccine was introduced, there were frequent errors in vaccine \nadministration. Dr. Talbot appreciates the debate surrounding the appropriateness of ICERs. \nShe is open to accepting higher ICERs, suggesting that other areas in medicine may be more suitable for cost savings. Additionally, she emphasized the importance of the working group returning to find a simplified standard vaccine that does not rely on shared clinical decision-making, as it has proven ineffective. \n58 \n \n    \n \n \n \n \n \n \n \n  \n  \n  \n    \n  \n \n   \n \n \n    \n  \n  \n  \n  \n \n \n  \n \n  \n    \n  \n \n   \n   \n \n \n \n \n \n \n Dr. Schechter inquired whether there w ere enough data to do a sensitivity analysis on the \npotential protection of gonococcal disease in young adults. \nDr. Schillie responded that the vaccine is anticipated to be licensed to prevent meningococcal \ndisease; however, it is known that these vaccines have about 30-40% efficacy against gonorrhea infections. This, however, was not factored into the cost-effectiv eness analysis, but \ntheoretically, this will make it more cost-effective when considering the benefits of gonorrhea prevention. \nDr. Sarah Schillie (CDC/NCIRD) introduced the MenB -4C ( BEXSERO) interval and dosing label \nchange. T\n…[truncated]", "summary": "MEETING OF THE ADVISORY  COMMITTEE ON IMMUNIZATION  PRACTICES (ACIP)  OCTOBER 23-24 , 202 4  MEETING SUMMARY  Trade names are used for identification purposes only and do not indicate endorsement.                                                                                                                                    WEDNESDAY : OCTOBER 23, 2024  WELCOME AND INTRODUCTIONS  Call to Order/Roll Call  Dr. Melinda Wharton (ACIP Executive Secretary) called the October 23, 2024, Advisory …", "source_url": "https://www.cdc.gov/acip/meetings/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/minutes/summary-2024-10-23-24-508.pdf", "doc_date": "2024-10-23", "case": "acip", "sub_case": "minutes", "tags": ["acip", "cdc", "vaccines", "minutes"], "page_count": 105}
{"title": "agenda 2024 06 26 28 508", "content": "Final - June 26, 2024\n8:00 Welcome & Introductions Dr. Keipp Talbot (ACIP Chair)\nDr. Melinda Wharton (ACIP Executive Secretary, CDC)\n8:30 Respiratory Syncytial Virus Vaccines - Adult \nIntroduction Dr. Camille Kotton (ACIP, WG Chair)\nAbrysvo (Pfizer) safety and immunogenicity in non-pregnant adults \naged 18-59 yearsDr. Iona Munjal (Pfizer)\nArexvy (GSK) immunogenicity with a 24-month revaccination interval Dr. Susan Gerber (GSK)\nmRNA-1345 (Moderna) Update on vaccine safety, efficacy and \nrevaccination dataDr. Rituparna Das (Moderna)\nPostmarketing safety updates: Vaccine Safety Datalink Dr. James Donahue (Marshfield Clinic Research Institute)\nEvaluation of Guillain-Barre Syndrome (GBS) following RSV \nvaccination among adults 65 years and olderDr. Patricia Lloyd (FDA)\n10:00 Break \n10:10 RSV Vaccines - Adult (continued)\nObservational RSV vaccine effectiveness Dr. Diya Surie (CDC, NCIRD)\nEconomic analysis of adult RSV vaccination Dr. David Hutton (University of Michigan)\nUpdate to benefits and risks discussion Dr. David Hutton (University of Michigan)\nComparison of economic analyses of adult RSV vaccination Dr. Ismael Ortega-Sanchez (CDC/NCIRD)\n11:30 Break \n11:40 RSV Vaccines - Adult (continued)\nEvidence to Recommendations Dr. Michael Melgar (CDC/NCIRD), Lauren Roper \n(CDC/NCIRD), Dr. Amadea Britton (CDC/NCIRD)\nClinical Considerations Dr. Michael Melgar (CDC/NCIRD)\n1:05 Break\n1:50 Combined Diphtheria and Tetanus Toxoids and Acellular Pertussis, \nInactivated Poliovirus, Haemophilus influenzae Type B Conjugate, \nand Hepatitis B vaccine (Vaxelis®)\nIntroduction Dr. Jamie Loehr (ACIP, WG Chair)\nEtR and proposed recommendations: Use of Vaxelis among American \nIndian and Alaska Native InfantsDr. Jennifer Collins (CDC/NCIRD)\nUpdated VFC resolution Dr. Jeanne Santoli (CDC/NCIRD)\n2:50 Break\n3:00 Public Comment \n3:20 VOTES \nRespiratory Syncytial Virus (RSV) Vaccines Votes Dr. Michael Melgar (CDC/NCIRD)\nVaxelis Dr. Jennifer Collins (CDC/NCIRD)\nVaxelis VFC Dr. Jeanne Santoli (CDC/NCIRD)\n4:10 Break\n4:20 Chikungunya Vaccine \nIntroduction Dr. Wilbur Chen (ACIP, WG Chair)\nUpdate on chikungunya vaccines Dr. Susan Hills (CDC/NCEZID)\nEpidemiology of chikungunya in U.S. territories and states Dr. Susan Hills (CDC/NCEZID)\nCost-effectiveness of use of live attenuated chikungunya vaccine \namong adults living in U.S. territories Dr. Kelly Kilburn, Dr. Erin Staples (CDC/NCEZID)\nNext steps for Work Group Dr. Susan Hills (CDC/NCEZID)\n5:20 Dengue Vaccines \nDengvaxia discontinuation Dr. Nicholas Bergren (Sanofi)\nDengue vaccine updates Dr. Joshua Wong (CDC/NCEZID)\n5:30 RecessMEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)\nCenters for Disease Control and Prevention\nAtlanta, Georgia 30329  \nJune 26-28, 2024\nWednesday, June 26, 2024\nFinal - June 26, 2024\n8:00 Welcome & Introductions Dr. Keipp Talbot (ACIP Chair)\nDr. Melinda Wharton (ACIP Executive Secretary, CDC)\n8:15 Agency Updates CDC, CMS, FDA, HRSA, IHS, OIDP, NIH\n8:35 COVID-19 Vaccine\nIntroduction Dr. Matt Daley (ACIP, WG Chair)\nCOVID-19-associated hospitalizations Dr. Fiona Havers (CDC/NCIRD)\nCOVID-19 vaccine effectiveness update Dr. Ruth Link-Gelles (CDC/NCIRD)\nVaccine safety update for 2023-2024 COVID-19 vaccine Dr. Jonathan Duffy (CDC/NCEZID)\nEconomic analysis of COVID-19 vaccination Dr. Lisa Prosser (University of Michigan)\nEtR for use of the 2024-2025 COVID-19 vaccine Dr. Lakshmi Panagiotakopoulos (CDC/NCIRD)\nCOVID-19 vaccine implementation Dr. Shannon Stokley (CDC/NCIRD)\n11:05 Break \n11:20 Influenza Vaccines\nIntroduction Dr. Jamie Loehr (ACIP, WG Chair)\nInfluenza A (H5N1) Update Dr. Vivien Dugan (CDC/NCIRD)\n12:00 Break\n1:00 Influenza Vaccines (continued)\nWG Considerations and Proposed Recommendations Dr. Lisa Grohskopf (CDC/NCIRD)\n2:00 Pneumococcal Vaccines \nIntroduction Dr. Jamie Loehr (ACIP, WG Chair)\nEconomic analysis and public health impact of PCV21 use in adults Dr. Charles Stoecker (Tulane University)\nComparison of economic analysis on PCV21 use in adults Dr. Andrew Leidner (CDC/NCIRD)\nSummary of WG Interpretation of EtR and policy options on PCV21 \nuse in adultsDr. Miwako Kobayashi (CDC/NCIRD)\nClinical considerations for PCV21 use in adults Dr. Miwako Kobayashi (CDC/NCIRD)\n3:55 Break \n4:10 Public Comment \n4:30 VOTES \nCOVID-19 Dr. Megan Wallace (CDC/NCIRD)\nPneumococcal Dr. Miwako Kobayashi (CDC/NCIRD)\nInfluenza Dr. Lisa Grohskopf (CDC/NCIRD)\n5:15 Recess\n8:30 Welcome & Introductions Dr. Keipp Talbot (ACIP Chair)\nDr. Melinda Wharton (ACIP Executive Secretary, CDC)\n8:55 Meningococcal Vaccines \nIntroduction Dr. Jamie Loehr (ACIP, WG Chair)\nEpidemiology Updates Ms. Amy Rubis (CDC/NCIRD)\nGSK Pentavalent Vaccine Immunogenicity and Safety Dr. Wendy Sohn (GSK)\nWG Considerations Regarding MenABCWY Vaccine and Discussion of \nPotential Risk Groups for MenB VaccinationDr. Sarah Schillie (CDC/NCIRD)\n10:00 Break\n10:15 Respiratory Syncytial Virus Vaccines - Maternal/Pediatric \nIntroduction Dr. Sarah Long (ACIP, WG Chair)\nImplementation and uptake of nirsevimab and maternal RSV vaccine Dr. Shannon Stokley (CDC/NCIRD)\nMaternal RSV vaccine safety surveillance Dr. Pedro Moro (CDC/NCEZID)\nSummary of effectiveness of nirsevimab in infants Dr. Amanda Payne (CDC/NCIRD)\nWork Group considerations Dr. Jefferson Jones, Dr. Katherine Fleming-Dutra \n(CDC/NCIRD)\n11:40 Human papillomavirus Vaccines \nAnnouncement of formation of an ACIP HPV vaccines work group Dr. Oliver Brooks (ACIP, WG Chair)\n11:50 AdjournFriday, June 28, 2024Thursday, June 27, 2024\nFinal - June 26, 2024\nAcronyms\nCDC Centers for Disease Control and Prevention\nCMS Centers for Medicare and Medicaid Services \nCOVID-19 Coronavirus disease 2019\nEtR Evidence to Recommendations Framework\nFDA Food and Drug Administration\nGRADE Grading of Recommendations Assessment, Development and Evaluation\nHRSA Health Resources and Services Administration\nHPV Human papillomavirus\nIHS Indian Health Service\nNCHHSTP National Center for HIV, Hepatitis, STD and TB Prevention\nNCIRD National Center for Immunization & Respiratory Diseases\nNCEZID National Center for Emerging and Zoonotic Diseases \nNIAID National Institute of Allergy and Infectious Diseases\nOIDP Office of Infectious Disease and HIV/AIDS Policy\nRSV Respiratory Syncytial Virus (RSV) \nSARS-CoV-2 Severe Acute Respiratory Syndrome Coronavirus 2\nWG Work Group\nWHO World Health Organization\nVE Vaccine Effectiveness", "summary": "Final - June 26, 2024 8:00 Welcome & Introductions Dr. Keipp Talbot (ACIP Chair) Dr. Melinda Wharton (ACIP Executive Secretary, CDC) 8:30 Respiratory Syncytial Virus Vaccines - Adult  Introduction Dr. Camille Kotton (ACIP, WG Chair) Abrysvo (Pfizer) safety and immunogenicity in non-pregnant adults  aged 18-59 yearsDr. Iona Munjal (Pfizer) Arexvy (GSK) immunogenicity with a 24-month revaccination interval Dr. Susan Gerber (GSK) mRNA-1345 (Moderna) Update on vaccine safety, efficacy and …", "source_url": "https://www.cdc.gov/acip/meetings/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/agendas/agenda-2024-06-26-28-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "agendas", "tags": ["acip", "cdc", "vaccines", "agendas"], "page_count": 3}
{"title": "summary 2024 06 26 28 508", "content": "MEETING OF THE ADVISORY \nCOMMITTEE ON IMMUNIZATION \nPRACTICES (ACIP) \nJUNE 26-28, 2024 \nMEETING SUMMARY \nTrade names are used for identification purposes only and do not indicate endorsement. \n \n   \n \n  \n \n \n \n       \n \n \n \n \n \n \n    \n \n     \n   \n   \n    \n \n \n  \n \n      \n  \n    \n \n   \n   \n     \n       \n \n     \n   \n   \n \n   \n   \n     \n \n \n \n   \n \n   \n \n  WEDNESDAY: JUNE 26 , 2024 \nWELCOME AND INTRODUCTIONS \nCall to Order \nDr. Keipp Talbot, ACIP Chair, called to order and presided over the June 26-28, 2024, Centers \nfor Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices \n(ACIP ) meeting. \nAnnouncements \nDr. Melinda Wharton, ACIP Executive Secretary, CDC , made opening announcements about \nthe availability of presentation slides on the ACIP website and scheduled oral public sessions as \nwell as the written public comment process.  She reviewed conflict of interest policies for ACIP members and indicated that CDC is currently soliciting applications and nominations for \ncandidates to fill upcoming vacancies on the ACIP for 4-year terms beginning July 2025. \nDetailed instructions for submission of names of potential candidates to serve as ACIP \nmembers are now available on the ACIP website. The deadline for applications is August 15, \n2024. \nShe welcomed the following 3 new members who were joining the ACIP meeting for the first \ntime and the new ACIP Chair: \nDenise Jamieson, MD, MPH who is the Vice President for Medical Affairs , Dean of the \nCarver College of Medicine, and Professor of Obstetrics and Gynecology at the University of \nIowa. Her scientific work is focused on emerging infections and vaccines in pregnancy . \nRobert Schechter , MD, MSc who is Chief of the California Department of Public Health \n(CDPH) in the I mmunization Branch where he has worked for over 20 years . He has served \npreviously on the N ational Vaccine Advisory C ommittee (NVAC) and on a number of \nACIP Work G roups (WG), including COVID -19, Influenza, and other vaccines . \nAlbert Shaw, MD, PhD, FIDSA who is Professor of Medicine in the Section of infectious \nDiseases at the Yale School of Medicine. Dr Shaw is an infectious disease physician whose \nfield of expertise is changes in the immune system function in older adults . \nKeipp Talbot, MD who is the new ACIP Chair. Dr. Talbot has been on ACIP since 2018 and \nis well known to most of the ACIP members . Dr. Talbo t is Professor of Medicine and Health \nPolicy in the Division of Infectious Diseases at Vanderbilt University . \nRoll Call Dr. Keipp Talbot, ACIP Chair , conducted a roll call, which established that a quorum was \npresent. A list of Members, Ex Officios, and Liaison Representatives is included in the \nappendixes at the end of this summary document. No conflicts of interest (COIs ) were identified \nfor the first day of this meeting. \n2 \n \n  \n \n \n \n \n \n  \n \n \n  \n  \n  \n \n \n   \n   \n  \n \n \n  \n \n \n \n \n \n \n  \n    \n  \n \n  \n   \n  \n    \n \n \n  \n   \n \n  PRESENTATIONS \nDr. Camille Kotton, Chair of the ACIP Adult Respiratory Syncytial Virus (RSV) Work Group, \nbegan the session by introducing the incoming chair of the work group, Dr. Albert Shaw.  Dr. Kotton reminded the committee of the current recommendation for use of RSV vaccine in adults that had been voted on by the committee in June 2023, that adults aged 60 years and older may receive a single dose of RSV vaccine, using shared clinical decision-making (SCDM).  This \nrecommendation was not product-specific, and whichev er vaccine was available could be \nadministered. She reviewed what had been covered at the February 2024 ACIP meeting, \nincluding an analysis comparing the estimated magnitude of public health benefit and potential \nrisk of Guill ain-Barré syndrome (GBS) associated with protein subunit RSV vaccination in adults \naged 60 years and older. ACIP recommended that adults 60 years and older who remain \nunvaccinated were encouraged to receive RSV vaccine in the late summer or early fall to \noptimize public health benefits.  \nSince the June meeting, the work group had discussed us e of Moderna’s mRESVIA ® in adults \naged 60 years and older (approved by FDA May 31, 2024) ; use of GSK’s AREXVY in adults \naged 50-59 years at increased risk of severe RSV disease (approved by FDA June 7, 2024); \nsafety of protein subunit RSV vaccines, including risk of GBS; and shifting from a shared clinic al \ndecision-making recommendation to an age-based recommendation for adults 75 years of age \nand older; a risk -based recommendation for adults 60-74 years of age; and a risk -based \nrecommendation for adults 50-59 years of age.  These proposed changes were informed by feedback received from healthcare providers on the challenges of implementing a recommendation based on shared clinical decision -making.  \nDr. Jim Donahue from the Marshfield Clinic Research Institute provided an update on the Vaccine Safety Datalink’s (VSD’s) rapid cycle analysis of RSV vaccines in older adults. The \nVSD is a collaborative project between CDC and 13 integrated healthcare organizations which \nhave data on approximately 13.5M persons.  Rapid cycle analysis (RCA) permits rapid \nassessment of vaccine safety by looking at the incidence of pre-specified outcomes in \nvaccinated persons compared to the incidence of those outcomes in a comparator group.  Sequential analytic methods are used to detect “statistical signals” while maintaining a pre-\ndefined type 1 error rate.  Statistical signals are interpreted as potential associations. The RSV RCA looked at persons ≥60 years of age who received an RSV vaccine, with a surveillance \nperiod from August 1, 2023, through May 31, 2025.  This RCA uses vaccinated concurrent \ncomparators, who are RSV vaccinees who on the same day as the exposed case in a risk \ninterval, were in the same demographic stratum, but in a comparison interval.  The RCA looked \nat both GSK and Pfizer RSV vaccines, with and without simultaneous vaccination and 14 pre-specified outcomes were evaluated.  From August 1, 2023 to May 25, 20 24, 385,729 doses of \nRSV vaccine were administered in the VSD sites, of which 87.7% was the GSK vaccine.  A \nstatistical signal was detected for immune thrombocytopenia (ITP) among recipients of the GSK \nvaccine without simultaneous vaccination, but most of the cases were not incident cases.  The RCA team plans to do more detailed chart review of ITP cases.  There was no statistical signal \nfor GBS (few cases were observed) or atrial fibrillation.  Surveillance for all outcomes will \ncontinue through May 2025. \nDr. Patricia Lloyd from the Office of Biostatistics and Pharmacovigilance, Center for Biologics \nEvaluation and Research (CBER), Food and Drug Administration (FDA), presented an update \non FDA’s evaluation of Guillain-Barré syndrome following RSV vaccination among adults 65 \nyears of age and older in fee-for-service Medicare.  \n3 \n \n  \n \n \n   \n   \n \n  \n \n \n \n   \n \n \n    \n \n  \n \n  \n \n \n  \n  \n \n  \n  \n  \n  \n   \n \n  \n \n \n \n  The risk of GBS following both GSK’s and Pfizer’s RSV vaccines was evaluated using a retrospective cohort design with a 2022 historical comparator.  The estimated observed \nincidence rates were compared to the historical comparator rates to obtain incidence rate ratios \n(IRRs) with 95% confidence intervals.  An adjustment for the positive-predictive value (PPV) of a \nGBS diagnosis code was made using an estimate of PPV of 71%, based on chart review. An \nelevated IRR was observed for GBS following RSV vaccination.  In the PPV -adjusted analysis, \nonly the association for the Pfizer vaccine was statistically significant. This is a crude method that utilized aggregate historical comparator rates, increasing the potential for confounding; \nstatistically significant results of GBS do not establish a causal association between RSV cases \nand GBS.  A self-controlled case series analysis was then undertaken.  Current results were based on an analysis of early -season vaccination.  An elevated IRR was observed for GBS \nfollow ing the Pfizer vaccine in two analyses that had the least adjustments; results additionally \nadjusted for PPV were no longer statistically significant.  T hese analyses do not provide clear, \nconclusive evidence of an elevated risk of GBS and an elevated risk cannot be ruled out; FDA is conducting medical chart review on GBS cases and will continue to evaluate the safety of RSV vaccines as more data are available. \nDr. Diya Surie from the Coronavirus and Other Respiratory Viruses Division (CORVD), CDC, \npresented on the effectiveness of adult RSV vaccines, 2023-2024.  In the IVY Network of 26 \nhospitals in 20 states, a test-negative, case-control design was used with an analysis period of October 1, 2023 to March 31, 2024.  Vaccine effectiveness (VE) was high against RSV -\nassociated hospitalization and similar among adults aged 60-74 years and ≥ 75 years.  In the \nVISION multi-site network of 245 emergency rooms and 230 hospitals, a test-negative design analysis was done based on electronic health records.  VE was high against RSV -associated \nemergency department (ED) visits, hospitalization, and critical illness. VE was similar among adults aged 60-74 years and ≥75 years for both outcomes.  VE point estimates decreased with \nincreases in time since RSV vaccination with limited follow -up time within the season.  Across \noutcomes, VE was similar between GSK and Pfizer RSV vaccines and RSV vaccines provided protection against RSV-associated hospitalizations among people with immunocompromise.  \nThe Veterans Administration used a target trial emulation that compared RSV vaccination (GSK \nor Pfizer) with no RSV vaccination for the prevention of documented RSV infection and RSV -\nassociat ed ED/urgent care (UC) visits or hospitalization among veterans ≥ 60 years of age. \nEnrollment was September 1-December 31, 2023, and follow up was extended through March \n31, 2024. VE was high against documented RSV infection, RSV -associated ED or UC visit, and \nRSV-associated hospitalization and did not differ between the two products.  An analysis of \nMedicare fee-for-service data for persons ≥65 years of age with end-stage renal disease \n(ESRD) sho wed that RSV vaccination provided protection against RSV -associated \nhospitalization among adults with ESRD on dialysis. Under real -world conditions, RSV \nvaccination (GSK or Pfizer) provided protection against severe RSV disease among US adults aged ≥60 years in this first season of use. These results provided evidence of VE against RSV -\nassociated ED visits, hospitalizations, and critical illness and demonstrated protection in a population that more closely represents those at high-risk of severe RSV disease. \n4 \n \n  \n  \n \n  \n  \n \n  \n \n \n \n  \n \n \n  \n \n \n \n    \n  \n  \n \n    \n   \n  \n \n \n  \n  \n \n \n \n  \n \n \n \n  \n  \n \n   \n  \n \n \n \n  Dr. David Hutton from the University of Michigan presented an economic analysis of RSV vaccination in adults 50 years and older.  The analysis looked at U.S. adults aged ≥ 50 years, \nstratified by age and chronic medical conditions and assumed that VE was reduced by half in \nimmune compromised populations, compared with others. The base case incremental cost-effectiveness analysis showed for all adults 75 years+ with protein subunit vaccines $51,447 per quality -adjusted life-year (QALY) and with Moderna’s RSV vaccine $66,287 per QALY; for \nadults 60-74 years of age with at least one risk condition, $60,933 for the protein subunit vaccines and $80,953 for the Moderna vaccine; and for adults 50-59 years of age with at least 1 \nrisk condition, $154,501 per QALY. Cost per QALY was much higher in all age groups among persons without underlying risk conditions.  Longer duration of protection (36 months rather than 24 months) or higher baseline RSV disease burden made all policy options more cost effective. \nDr. Hutton presented a second analysis that compared the estimated benefits of RSV \nvaccination and the potential risk of GBS after protein subunit RSV vaccination (GSK or Pfizer).  \nThis analysis found that the estimated numbers of avertable deaths are much larger than potential GBS cases for adults 75 years of age and older and for adults 60-74 years of age with at least one risk condition.  The estimated numbers of avertable deaths are larger, but more similar in magnitude, than potential GBS cases for adults 50- 59 with at least one chronic \ncondition and adults 60- 74 without chronic conditions. \nDr. Ismael Ortega-Sanchez , CDC, presented a summary comparing economic models from \nGSK, Moderna, and the University of Michigan (UM) with CDC. Differences in key inputs and \nassumptions among the three models explain differences in results.  The resulting incremental cost-effectiveness ratios vary by age and high-risk group.  For vaccinating all adults ≥75 years \nagainst RSV, Moderna and UM -CDC models reported societal costs between $51K and $66K \nper QALY saved. For vaccinating adults aged 60-74 years at higher risk of severe RSV disease, Moderna and UM -CDC models reported societal costs between $61K to $89K per \nQALY saved.  For vaccinating adults aged 50-59 years at higher risk, the results were more discrepant, ranging from societal cost -saving (GSK) to $154K per QALY saved (UM -CDC). \nThe Evidence to Recommendations Framework (EtR) for RSV vaccination in adults aged 50-59 years, 60-74 years, and 75 years and older was presented by Drs. Amadea Britton and Michael Melgar and Ms. Lauren Roper, CORVD. The work group interpretation was that RSV was a public health problem for adults ≥60 years of age.  The annual rate of RSV -associated \nhospitalization increases with increasing age, with a steep rise at age 75 years.  Certain chronic \nmedical conditions also increase risk of RSV -associated disease; age and chronic medical \nconditions are independently associated with increased risk.  RSV is associated with severe \ndisease and has significant post-hospitalization sequelae among older adults.  Evidence for \nbenefits and harms was presented, and the work group interpretation was that desirable effects outweighed undesirable effects for both protein subunit and Moderna’s RSV vaccine in adults \n≥75 years of age and in adults 60-74 years at increased risk. The evidence for values, \nacceptability, feasibili ty, and resource use also supported use of RSV vaccines in both groups, \nand the work group felt that RSV vaccine would likely have a positive impact on health equity in \nboth groups, with support overall for use of RSV vaccine in both groups. The work group felt that there was sufficient information to move forward with a recommendation, and recommended that adults 75 years of age and older receive a single dose of RSV vaccination, \nand adults 60-74 years of age who are at increased risk for severe RSV disease receive a single dose of RSV vaccination. \n5 \n \n  \n \n  \n   \n  \n \n \n \n \n  \n \n \n  \n  \n  \n  \n   \n \n \n  \n \n \n    \n  \n \n  \n   \n  \n \n \n  \n   \n    \n \n  \n \n \n \n \n  \n  \n  \n    Next the EtR for use of RSV vaccine in adults 50-59 years at increased risk of severe RSV \ndisease was presented.  The work group felt that RSV in this group was or probably was a \npublic health problem but thought that it was unclear whether or not desirable effects \noutweighed undesirable effects.  As of the June 2024 ACIP meeting, the work group majority \nhad concluded that there is currently insufficient evidence to make a recommendation regarding RSV vaccination in adults 50-59 years of age. Before making a recommendation for adults 50-59 years, the work group would like to review additional data, including at least one complete season of safety surveillance data; immunobridging data in adults with immune compromise; \nand data on duration of protection and immune response after revaccination. \nClinical considerations included discussion of chronic medical conditions associated with \nincreased risk of severe RSV disease.  These included lung disease; cardiovascular disease; moderate or severe immune compromise; diabetes mellitus with end-organ damage; sever e \nobesity; neurologic or neuromuscular conditions; advanced chronic kidney disease; liver disorders; hematologic disorders; and other chronic medical conditions that a healthcare provider determines increase the risk of severe disease due to respiratory infection. This might \ninclude residence in a nursing home or other long-term care facility; frailty; or other individual \nfactors determined by the clinician to increase risk of severe respiratory infection. In \naccordance with CDC’s General Best Practices for Immunization, coadministration of RSV \nvaccines with other adult vaccines is acceptable. \nDr. Jamie Loehr moved that ACIP recommend that adults who are 75 years of age and older \nreceive a single dose of RSV vaccine.  The motion was seconded by Dr. Sara Long.  Dr. Loehr moved that ACIP recommend adults 60-74 years of age who are at increased risk of severe \nRSV disease, as described in CDC’s clinical guidance, receive a single dose of RSV vaccine.  \nThe motion was seconded by Dr. Camille Kotton. \nThe next topic was preferential use of Combined Diphtheria and Tetanus Toxoids and Acellular \nPertussis, Inactivated Poliovirus, Haemophilus influenzae Type B Conjugate, and Hepatitis B \nvaccine (VAXELIS\n®) in American Indian and Alaska Native (AI/AN) infants.  Dr. Jamie Loehr, \nChair of the ACIP Hib/Meningococcal Vaccines Work Group, opened the session with \nbackground on the existing recommendation for use of PRP-OMP (PedvaxHIB®) in AI/AN \ninfants because it provides a protective antibody response after the first dose and historically, \nHib meningitis peaked at an earlier age among AI/AN infants.  VAXELIS® (DTaP -IPV- Hib-HepB) \ndid not have a preferential recommendation for AI/AN infants because it contains PRP -OMP in a \nlower amount than in PedvaxHIB® and post-dose 1 immunogenicity data were not previously \navailable. At the February ACIP meeting, clinical trial data on post-dose 1 immunogenicity of \nVAXELIS® vs. PedvaxHIB® were presented along with preliminary work group considerations. \nThe EtR for use of VAXELIS® among AI/AN infants was presented by Dr. Jennifer Collins, CDC.  \nThe work group determined that invasive Hib disease is a public health problem among AI/AN populations and that the desirable effects outweighed the undesirable effects, favoring use of \nVAXELIS\n® or PedvaxHIB®. Dr. Collins described a listening session with tribal communities that \nNCIRD held in collaboration with CDC’s Office of Tribal Affairs and Strategic Alliances in January 2024.  Key questions and concerns raised by participants for work group consideration were whether or not VAXELIS\n® would provide the same protection as PedvaxHIB®; the need to \nmonitor for possible breakthrough cases, and safety and side effects.  The work group felt that available evidence in the domains of values, acceptability, feasibility, and resource use were \nsupportive or probably were supportive, and that the impact of using VAXELIS\n® among AI/AN \ninfants on health equity were moderate or large. \n6 \n \n  \n \n  \n \n \n \n    \n \n   \n \n \n  \n   \n \n \n \n \n  \n \n     \n  \n     \n \n \n \n \n  \n \n  \n \n \n    \n   \n \n  \n \n   The majority of the work members judged that the desirable consequences probably outweigh undesirable consequences in most settings and proposed that ACIP recommend that DTaP -\nIPV-HepB ( VAXELIS\n®) should be included with PRP -OMP ( PedvaxHIB®) in the preferential \nrecommendation for AI/AN infants based on the Haemophilus influenzae type b (Hib) \ncomponent.  \nDr. Loehr made a motion that ACIP recommend that DTaP -IPV-HepB ( VAXELIS®) should be \nincluded with PRP-OMP ( PedvaxHIB®) in the preferential recommendation for AI/AN infants \nbased on the Haemophilus influenzae type b (Hib) component. Dr. Long seconded the motion. \nDr. Jeanne Santoli, Immunization Services Division, CDC, then presented a proposal to update \nthe Recommended Vaccination Schedule and Intervals section of the Vaccines for Children \n(VFC) resolution to add a preference for VAXELIS® in children who are AI/AN and to better align \nwith the existing ACIP recommendations.  \nDr. Loehr made a motion to approve the VFC resolution for vaccines to prevent Haemophilus \ninfluenzae type b (Hib) and it was seconded by Dr. Sybil Cineas. \nPUBLIC COMMENTS \nOverview \nThe floor was opened for public comment on June 26, 2024 at 3:40 PM E DT. Members of the \npublic also were invited to submit written public comments to ACIP through the Federal \neRulemaking Portal under Docket Number ID CDC-2024-0043. Visit regulations.gov to read \nbackground documents and comments received. \nPublic Comments \nMr. Noah Louis-Ferdinand \nCommunications Coordinator \nVoices for Vaccines \nMr. Louis -Ferdinand made comments about the shared clinical decision- making \nrecommendation for RSV vaccine for people 60 and over, which he said was confusing.  SCDM doesn't really give clear guidance on what people should or shouldn't do , on top of \nrecommendations for updated COVID -19 vaccines, which people also find confusing. Clear \nmessaging would be very helpful it would go a long way to have that clear recommendation, given that this is a serious and burdensome disease for the public . \n7 \n \n  \n \n    \n \n  \n     \n  \n    \n    \n     \n       \n  \n   \n   \n   \n \n \n  \n  \n \n   \n \n  \n  \n      \n   \n   \n     \n  \n   \n  \n     \n  \n \n \n \n   \n  \n \n     \n  \n   \n \n      \n   \n  \n       \n  \n       \n  Dorit Reiss, PhD \nProfessor of Law \nUniversity of California (UC) Law San Francisco \nMs. Reiss spoke in favor of combination vaccines as a parent, because fewer injections are \nrequired. She agreed with the previous commenter about the need for simplicity and clarity in \nrecommendations . Because the Vaccine for Adults program is not on the immediate h orizon, \ntaking away shared clinical decision-m aking for adults under 75 will create serious equity issues \nfor those who cannot afford a $400 vaccine. She mentioned two recent legal decisions that \nmight affect the committee’s or CDC’s work .  In a recent decision in Braidwood v Becerra, the \nFifth C ircuit implied at least that it may consider previous ACIP recommendations as \nunconstitutional , given the lack of approval. In Murthy versus Missouri , the Supreme Court \nrejected the challenge to CDC ’s and other agencies ’ communications with government and \nsocial media on the grounds that they didn't show the communication led directly to effects, \nwhich could open the door to more c ommunication between CDC and social media platform s. \nElias Kass, ND \nNaturopathic Physician\nPediatric Primary Care and Vaccine Hesitancy \nDr. Kass spoke in favor of including babies and young children in this fall’s updated COVID \nvaccine recommendations and asked that primary care offices be supported in distribution and \nadministration of these vaccines as most young children cannot be vaccinated in pharmacies . \nDr. Kass also expressed his hope that the authorization for Novavax authorization would be \nextended down to 6 months because many families in his practice who otherwise \nenthusiastically vaccinate are still apprehensive about mRNA vaccines and their children are \nexperiencing multiple COVID infections as there are no other options for this age group. He \ncalled on CDC to emphasize layered prevention , including engineering controls like clean indoor \nair as well as individual controls like masks and not rest on a vaccine only approach. These \napproaches would also help with other respiratory viruses like RSV . The rollout of nirsevimab in \nthe 2023-2204 season was eagerly anticipated and incredibly frustrating; he expressed hope \nthat this year will be smoother and that it was exciting to have ABRYSVO® for use in pregnancy , \nas RSV disease in infants remains a significant burden and contributes to a lifetime of \ncomplications. \nLindsay Clarke, JD\nSenior Vice President, Health Education and Advocacy\nAlliance for Aging Research \nMs. Clarke stated that when the ACIP delays a vote because they think they need more data, \nthe committee is inadvertently hampering vaccine data collection because new vaccines won’t \nbe used without an ACIP recommendation.  Ms. Clarke said that ACIP should get rid of its RSV \nand pneumococcal vaccine shared clinical decision-making recommendations for older adults . A \nreport that was recently released by Champions for Vaccine Education, Equity , Progress \n(CVEEP) found that SCDM vaccine recommendations create complex and unnecessary access \nhurdles , particularly for underserved communities . She also stated that her organization would \nlike to see ACIP vote on a universal RSV vaccination for all adults ages 60 and older and for the \nRSV vaccine that received FDA approval for expanded use in adults ages 50 and older . \nAdditionally, ACIP should vote on a universal pneumococcal vaccine recommendation for adults \nages 50 and older. \n8 \n \n  \n   \n \n  \n \n \n \n \n \n \n     \n    \n \n \n \n \n \n \n  \n  \n \n \n    \n \n     \n   \n \n \n \n \n \n \n  \n \n \n  \n \n \n      \n  \n        \n       \n \n \n  She also asked the committee to continue to support a preferential recommendation for enhanced flu vaccines and to vote as soon as possible after the FDA approves or authorizes the \n2024-2025 COVID -19 vaccines; her organization would like to see updated vaccines available \nin August on the same timeframe as annual flu vaccines . \nVOTES \nDr. Keipp Talbot, ACIP Chair , requested that the language for the votes be displayed for the \nrecommendation and VFC votes. \nVote #1: RSV Vaccine in A dults ≥75 Years of Age \nDr. Talbot read the following proposed ACIP voting language into the record for RSV v accine in \nadults ≥75 y ears of a ge: \nACIP recommends adults 75 years of age and older receive a single dose of RSV \nvaccine.\na,b \na. RSV vaccination is recommended as a single lifetime dose only. Persons who have already received RSV \nvacci\nnation are NOT recommended to receive another dose. \nb. This rec\nommendation would supplant the current recommendation that adults 60 years of age and older may receive \nRSV vaccination, using shared clinical decision-making. Adults 60–74 years of age who are not at increased risk of \nsevere RSV disease would NOT be recommended to receive RSV vaccination. \nMotion/Vote #1: RSV Vaccine in Adults ≥75 Years of Age \nDr. Loehr made a motion to approve the proposed recommendation RSV v accine in adults ≥75 \nyears of a ge as written stating: \n“ACIP recommends adults 75 years of age and older receive a single dose of RSV vaccine.a,b \na. RSV vaccination is recommended as a single lifetime dose only. Persons who have already received RSV vaccination are NOT \nrecommended to receive another dose. \nb. This recommendation would supplant the current recommendation that adults 60 years of age and older may receive RSV \nvaccination, using shared clinical decision-making. Adults 60–74 years of age who are not at increased risk of severe RSV \ndisease would NOT be recommended to receive RSV vaccination. ” \nDr. Long seconded the motion. No COIs were declared. The motion carried with 11 favoring, 0 \nopposing, and 0 abstaining. The disposition of the vote was as follows: \n11 Favored: Brooks, Chen, Cineas, Daley, Jamieson, Kotton, Loehr, Long, Schechter, \nShaw, Talbot \n0 Opposed: N/A \n0 Abstained: N/A \n9 \n \n      \n   \n \n \n \n  \n \n \n  \n  \n \n \n \n  \n \n   \n     \n \n \n \n \n \n \n \n  \n  \n \n \n    \n   \n \n      \n  \n        \n       \n  \n \n \n \n  \n \n      \n    \n   \n    \n   \n     \n     \n   \nVote # 2: RSV in Adults 60– 74 Years of Age at I ncreased Risk of Severe RSV Disease \nDr. Talbot, ACIP Chair , read the following proposed ACIP voting language into the record for \nadults 60– 74 years of age who are at increased risk of severe RSV disease: \nACIP recommends adults 60– 74 years of age who are at increased risk of severe RSV \ndiseasec receive a single dose of RSV vaccine.a,b \na. RSV vaccination is recommended as a single lifetime dose only. Persons who have already received RSV \nvaccination are NOT recommended to receive another dose. \nb. This recommendation would supplant the current recommendation that adults 60 years of age and older may receive \nRSV vaccination, using shared clinical decision-making. Adults 60–74 years of age who are not at increased risk of severe RSV disease would NOT be recommended to receive RSV vaccination. \nc. CDC will publish Clinical Considerations that describe chronic medical conditions and other risk factors for severe \nRSV disease for use in this risk-based recommendation. \nMotion/Vote #2: RSV Adults 60– 74 Years of Age at Increased Risk of Severe RSV Disease \nDr. Loehr made a motion to approve the proposed recommendation in adults 60– 74 years of \nage at increased risk of severe RSV d isease as written stating: \n“ACIP recommends adults 60– 74 years of age who are at increased risk of severe RSV \ndiseasec receive a single dose of RSV vaccine.a,b \na. RSV vaccination is recommended as a single lifetime dose only. Persons who have already received RSV vaccination are NOT \nrecommended to receive another dose. \nb. This recommendation would supplant the current recommendation that adults 60 years of age and older may receive RSV \nvaccination, using shared clinical decision-making. Adults 60–74 years of age who are not at increased risk of severe RSV \ndisease would NOT be recommended to receive RSV vaccination. \nc.  CDC will publish Clinical Considerations that describe chronic medical conditions and other risk factors for severe RSV disease \nfor use in this risk-based recommendation. ” \nDr. Kotton seconded the motion. No COIs were declared. The motion carried with 11 favoring, 0 \nopposing, and 0 abstaining. The disposition of the vote was as follows: \n11 Favored: Brooks, Chen, Cineas, Daley, Jamieson, Kotton, Loehr, Long, Schechter, \nShaw, Talbot \n0 Opposed: N/A \n0 Abstained: N/A \nDr. Talbot invited v oting members to make comments following the votes. \nDr. Loehr said he realized when talking to people that the general public might not know why the \nACIP is so concerned about GBS . For those who do not know, he explained that GBS is a \nneurological disorder with ascending paralysis. Patients who have it often end up in the hospital \nfor 3 to 4 months , might be intubated, and might die. Therefore, it is not a small consequence. It \nis not fevers or a febrile seizure. This is why the ACIP has such significant concerns about the \npossible risk of GBS with RSV vaccine. That is why he was much more comfortable with the \nrisk-based rather than the a ge-based recommendation for persons 60─ 74 years of age. \n10 \n \n      \n    \n  \n  \n     \n  \n    \n \n   \n  \n \n \n \n  \n  \n \n \n  \n \n  \n  \n  \n   \n   \n  \n \n      \n   \n        \n       \n \n \n  Dr. Daley noted that when Dr. Talbot was reading the language, he felt like adding “at this time” \nto both of those sentences. He just wanted to acknowledge that and make sure it is conveyed \nbecause that is based on what is known at this time. To Dr. Loehr’s point for the listening public , \nGBS is quite a serious condition. Fortunately , it is rare and more data are being gathered about \nit. For those who are recommended for an RSV vaccine at this time, that recommendation is \nbecause they will receive substantial benefit and avoid a serious illness that may put them in the \nhospital . There are many opportunities for disease prevention that should be implemented. \nVote: DTaP -IPV-Hib -HepB ( VAXELIS®)\nDr. Keipp Talbot, ACIP Chair , read the following proposed ACIP voting language into the record \nfor DTaP -IPV-Hib-HepB ( VAXELIS®): \nACIP recommends DTaP-IPV-Hib -HepB (Vaxelis®) should be included with \nPRP-OMP (PedvaxHIB®) in the preferential recommendation for American \nIndian and Alaska Native infants based on the Haemophilus influenzae type b (Hib) Hib component. \nMotion/Vote: DTaP -IPV-Hib -HepB (VAXELIS®) \nDr. Loehr made a motion to approve the proposed recommendation for chikungunya vaccines \nstating, “ACIP recommends DTaP-IPV-Hib -HepB ( VAXELIS®) should be included with PRP-\nOMP (PedvaxHIB®) in the preferential recommendation for American Indian and Alaska Native \ninfants based on the Haemophilus influenzae type b (Hib) Hib component.” Dr. Long seconded \nthe motion. No COIs were declared. The motion carried with 11 favoring, 0 opposing, and 0 \nabstaining. The disposition of the vote was as follows: \n11 Favored: Brooks, Chen, Cineas, Daley, Jamieson, Kotton, Loehr, Long, Schechter, \nShaw, Talbot \n0 Opposed: N/A \n0 Abstained: N/A \n11 \n \n    \n  \n \n \n \n \n \n \n   \n  \n   \n    \n \n \n      \n  \n        \n        \n \n \n \n  \n   \n \n  \n \n \n \n  \n   \n \n  \n  \n  \n \n \n Vote: VFC Resolution for DTaP -IPV-Hib -HepB (VAXELIS®)\nDr. Keipp Talbot, ACIP Chair , read the following proposed ACIP voting language into the record \nfor the VFC Resolution for d iphtheria, tetanus, and p ertussis vaccines : \nApprove the Vaccines for Children (VFC) Resolution for vaccines to prevent \nHaemophilus influenzae type b (Hib) . \nMotion/Vote: VFC Resolution for Diphtheria, Tetanus, and Pertussis Vaccines \nDr. Loehr made a motion to approve the proposed recommendation for the VFC Resolution \nstating, “Approve the Vaccines for Children (VFC) Resolution for vaccines to prevent Haemophilus influenzae type b (Hib) .” Dr. Cineas seconded the motion. No COIs were declared. \nThe motion carried with 11 favoring, 0 opposing, and 0 abstaining. The disposition of the vote \nwas as follows: \n11 Favored: Brooks, Chen, Cineas, Daley, Jamieson, Kotton, Loehr, Long, Schechter, \nShaw, Talbot \n0 Opposed: N/A \n0 Abstained: N/A \nThe next session began with a report from the ACIP Chikungunya Vaccines Work Group \npresented by Dr. Wilbur Chen.  The work group has been developing policy options for ACIP’s \nconsideration for use of chikungun ya vaccine among U.S. persons at risk of chikungunya, \nincluding travelers, laboratory workers, and residents of U.S. territories and states with risk of \ntransmission.  In February 2024 the work group recommended use of the live attenuated \nchikungunya vaccine among U.S. travelers and laboratory workers. \nDr. Susan Hills, Division of Vector-Borne Diseases (DVBD), CDC, then provided an update on \nchikungunya vaccines.  Bavarian Nordic has reported that their Biologics License Application \n(BLA) for their virus -like particle vaccine has been filed with FDA and the product could be \nlicensed in the first half of 2025.  They are requesting licensure of a single dose schedule for \nadolescents and adults ≥ 12 years of age.  Valneva’s chikungunya vaccine, IXCHIQ, was \nlicensed by FDA in November 2023 for use in a single dose schedule in adults ≥18 years.  \nDr. Hills also provided an update on the epidemiology of chikungunya in U.S. territories and \nstates with risk of transmission.  Chikungunya is a mosquito-borne disease; key vectors are \nAedes aegypti and Aedes albopictus mosquitoes.  Chikungunya typically occurs in tropical and \nsubtropical regions where it periodically causes large outbreaks, often with high attack rates.  Virus transmission is usually highest during the wet season of the year.  Acute chikungunya virus in fection is a febrile illness typically with severe arthralgia (joint pain), which can be \ndebilitating.  Other symptoms can include headache, rash, myalgia, and anorexia. In the absence of specific antiviral treatment, the approach to management typically involves rest, fluids, and use of analgesics and antipyretics. Serious complications are rare but can include myocarditis, hepatitis, and neurologic illnesses such as Guillain-Barré syndrome and \nmeningoencephalitis. Deaths are also rare and are reported mostly in older adults, particularly \nthose with comorbidities, and young infants infected perinatally or by mosquito bites. Acute \nsymptoms of chikungunya usually resolve in about 7 to 10 days. However, some patients have \na continuation or relapse of their joint symptoms in the months after acute illness and experience other symptoms such as fatigue. \n12 \n \n  \n \n \n \n \n  \n \n \n \n   \n  \n \n  \n \n  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n  \n \n \n \n \n \n  \n \n  Up to one-half of patients might have ongoing arthralgia of variable severity at 3 months after \ninfection and up to about 30% at 12 months after infection. \nIn the Caribbean region, chikungunya emerged in December 2013 with the first case reported in \nSaint Martin island. Subsequently there was a rapid increase in countries and territories \nreporting virus transmission. In Puerto Rico, the first locally acquired, laboratory -confirmed case \nof chikungunya occurred in early May 2014.  There was a rapid increase in the number of cases with the outbreak peaking in September 2014. In 2015 there was a small increase in cases in \nthe middle of the year when the weather in Puerto Rico is hot and humid and rainfall is heaviest but there was no substantial transmission after 2014. In Puerto Rico in terms of age groups, \nthere was a higher percentage of cases in children aged 0-19 years (42%) and lower but similar \npercentages of cases in the other age groups, although the higher percentage of cases in children might have been biased by laboratory testing practices.  Cases occurred in almost all \nareas of the island. Seroprevalence surveys suggest that about a million persons were infected \nduring the outbreak, translating to an estimated 650,000-850,000 clinical cases of chikungunya.  \nThe first locally acquired case of chikungunya in the U.S. Virgin Islands was in June 2014 on the \nisland of Saint Thomas.  The outbreak in Saint Thomas was followed by outbreaks on St. John \nand on St. Croix.  The last laboratory -positive case was in February 2015.  A seroprevalence \nsurvey approximately oe year after the outbreak ended showed that 31% of persons had \nevidence of past infection, translating to an estimate of 33,000 persons infected and 21,000-28,000 clinical cases during the 8-month outbreak period. \nIn American Samoa, an outbreak began in June 2014.  The extent of the outbreak is unclear, \nbut unconfirmed reports suggested at least 823 suspected cases occurred. The duration of the \noutbreak is also unclear but there was no evidence of ongoing transmission by the end of 2015 when a Zika outbreak began there.  Chikungunya has not been reported in the other U.S. territories, Guam and the Commonwealth of the Northern Mariana Islands.  An outbreak occurred in the Federated States of Micronesia in Yap State August 2013 to August 2014.  An \nattack rate of 155 clinical cases per 1,000 population was reported; about 15% of the population \nsought care for suspected illness.  An outbreak began in the Marshall Islands in February 2015; the duration and extent are unclear but there may have been >1,000 suspected cases. \nIn summary, among 8 US territories or affiliated states, 3 territories and 2 affiliated states have \nhad outbreaks of chikungunya. When outbreaks occurred, they were explosive and spread \nrapidly. For Puerto Rico and USVI, where information is available, seroprevalence surveys \nsuggest about 30% of the population was infected, which equates to about 20-25% of the \npopulation having clinical illness, with most cases occurring during a peak transmission period of about 6 months. All outbreaks in the US territories and freely associated states began from 2013– 2015, and the last evidence of any ongoing confirmed transmission was in 2017 in Puerto \nRico and was much earlier in the smaller island nations. Finally, the timing of future transmission or outbreaks is unknown, and the likely patterns of transmission in future cannot be predicted with certainty. \nThe first local transmission of chikungunya virus in the continental United States occurred in \nFlorida in 2014. This occurred at the time an extensive outbreak of chikungunya was ongoing in \nthe Americas and the US had seen a dramatic increase in chikungunya cases among travelers \nreturning to the United States. After the first locally acquired case was identified in June, 11 \nadditional cases were reported, and all occurred in four counties in southern Florida . Two \npatients lived with 1,500 feet of each other and were assumed to be linked as part of a cluster, and the others all appeared to be sporadic cases. \n13 \n \n   \n   \n \n  \n \n \n \n  \n \n \n    \n  \n \n  \n \n \n \n   \n \n   \n  \n   \n   \n \n \n   \n      \n \n  \n   \n     \n  \n \n \n  No local transmission of chikungunya virus in Florida has been reported since that time. An \nadditional case of locally acquired chikungunya occurred in Cameron County , Texas, in \nNovember 2015. The county is on the border with Mexico, but the patient denied any \ninternational travel prior to illness onset. No additional cases were identified. \nDr. Kelly Kilburn, CDC, presented an analysis of the cost-effectiveness of using a single dose of \nthe live attenuated chikungunya vaccine among the population aged 18 years and older living in \nUS territories that previously experienced an outbreak.  A population-based model was used \nwith an analytic time horizon of 30 years.  There are little data on the time between chikungunya \noutbreaks in island nations or territories. A modeling study in the Philippines estimated an \naverage of 17 years between outbreaks. Since the last outbreaks in the territories were in 2014, it was assumed that there would be one chikungunya outbreak in 2034.  Two strategies, routine vaccination with 20% annual vaccination coverage and outbreak vaccination were evaluated.  \nThe outbreak strategy averted 67% of health outcomes and the routine strategy averted 90% of \nhealth outcomes.  More doses are delivered during the 30-year time horizon in the routine strategy , resulting in higher vaccination costs of $436 million while the outbreak strategy has a \ncost of $356 million. In terms of total societal costs, vaccination in either strategy leads to lower net costs than without vaccination because of the large number of health outcomes averted. \nDr. Hills then provided an overview of next steps for the work group, which will continue gather \ndata and discuss use of chikungunya vaccine in at-risk U.S. territories, including acceptability and value of vaccine to providers and relevant populations and feasibility of administration.   The work group will also be considering recommendations for residents of U.S. states with risk and recommendations for use of the virus -like particle vaccine in travelers, laboratory workers, \nresidents of U.S. territories with risk, and residents of U.S. states with risk. \nThe next session was on dengue vaccines.  It began with an update from Dr. Nicholas Bergren, \nSanofi, who provided an update on the discontinuation of Dengvaxia\n®, Sanofi’s dengue vaccine.  \nDengvaxia® was indicated for the prevention of dengue disease caused by dengue virus \nserotypes 1, 2, 3 and 4 and was approved for use in individuals 6 through 16 years of age with laboratory -confirmed previous dengue infection and living in endemic areas. In 2021, ACIP \nrecommended vaccination with the Dengvaxia\n® vaccine for children aged 9– 16 years having \nevidence of a previous dengue infection and living in areas where dengue is endemic. Dengvaxia\n® wss recommended as a 3-dose vaccination series, administered 6 months apart (at \nmonth 0, 6, and 12) for the selected pediatric population. Evidence of previous dengue infection, \nsuch as confirmation with previous laboratory -confirmed infection or a highly specific \nserodiagnostic test, w as required among eligible children before vaccination. Dengvaxia® is \nbeing discontinued due to low demand; the decision was not due to any concerns regarding quality, safety, or efficacy.  Dengvaxia\n® will continue to be distributed through public (e.g., \nVFC) and private markets globally (including Puerto Rico where it is currently recommended by \nthe ACIP) through product expiry. The last doses of Dengvaxia® will expire at the end of August \n2026. Given the 3-dose, 1-year series needed for full immunization, individuals should start the Dengvaxia\n® immunization series no later than August 31, 2025. \nDr. Joshua Wong, Dengue Branch, DVBD, NCEZID, then provided an update on dengue vaccines and epidemiology.  Many countries including the U.S. have reported locally acquired \ndengue cases during the period March 2023 to April 2024.  As of June 25, 2024, nearly 10 million cases have been reported in the Americas in 2024.  Dengue is endemic in 6 U.S. territories and freely associated states.  Puerto Rico declared a public health emergency due to a dengue outbreak in March 2024; dengue infections have been above the epidemic threshold for 21 weeks.  Dengvaxia\n® was used in Puerto Rico, beginning in September 2022.  \n14 \n \n   \n  \n   \n  \n \n \n \n \n  \n \n    \n  \n \n  \n \n \n \n \n \n   \n \n \n \n \n \n     \n \n \n \n \n   \n  \n   \n     \n  \n \n    \n     \n    \n   \n     \n        \n   \n \n Since that time, 264 doses have been administered to 145 individuals, only 32 of whom completed the three dose series.  With the requirement for laboratory confirmation of prior \ninfection, multiple visits to healthcare providers were required to determine eligibility and start \nvaccination; this greatly complicated implementation.  Major barriers to update included \nprevaccination testing, complex billing processes, and limited messaging about the vaccine.  \nCDC has updated its website with information about the discontinuation of Dengvaxia\n®. \nNo dengue vaccines will be available in the U.S. after the discontinuation of Dengvaxia®. \nTakeda voluntarily withdrew TAK -003 (Qdenga) from FDA review in July 2023.  The \nTV003/TV005 dengue vaccine is in late-stage phase 3 trials.  This vaccine was developed by the U.S. National Institutes of Health and was licensed to Merck in the U.S. and the Instituto Butantan in Brazil.  Phase 3 trials in Brazil are ongoing.  Data from the first two years of follow-up have been published, showing high efficacy and safety.  DENV -3 or DENV -4 have not been \nobserved during this period, limiting evaluation of VE against these serotypes.  Five -year follow -\nup data are expected later this year. The ACIP Dengue Vaccines Work Group will be paused until new dengue vaccines are submitted to FDA for approval. Vaccines are just one part of a multilayered approach to reducing morbidity by dengue; people can continue to protect themselves and their families from dengue by preventing mosquito bites and controlling \nmosquitoes in and around their homes. \nWith no additional business posed for the day, the ACIP meeting stood in recess until 8:00 AM \non June 27, 2024. \nTHURSDAY: JUNE 27, 2024 \nWELCOME AND INTRODUCTIONS \nCall to Order \nDr. Keipp Talbot, ACIP Chair , called to order and presided over the second day of the June 26-\n28, 2024 ACIP meeting. \nAnnouncements Dr. Melinda Wharton (ACIP Executive Secretary, CDC) welcomed and introduced the 4\nth new \nmember of the ACIP , Yvonne (Bonnie) Mald onado, MD. Dr. Maldo nado is Ch ief of the D ivision \nof Infectious Diseases in the Department of Pediatrics at Stanford University, Director of \nStanford's Global Child Health Program , and serves as Medical Director for Infection Prevention \nand Control at the Children's Hospital at Stanford University . \nDr. Wharton also acknowledged the long service of Dr. William Schaffner from Vanderbilt \nUniversity who recently concluded a more than 40-y ear engagement with the ACIP. Dr \nSchaffner started his service in the early 1980s when he was a member of the AC IP from 1982 \nto 1986. Following, he served as a liaison representative for the American College of Physicians \n(ACP), the American Hospital Association (AHA), the Infectious Diseases Society of America \n(IDSA), and the National Foundation for Infectious Diseases (NFID). Dr. Schaffner responded \nthat his long association with the ACIP continues to be one of the most rewarding aspects of his \nprofessional career . \n15 \n \n  \n \n   \n \n       \n \n \n \n \n \n \n   \n    \n   \n   \n   \n    \n   \n   \n  \n \n  \n  \n \n  \n   \n \n   \n    \n   \n   \n   \n \n     \n \n  \n \n  \n \n    \n \n \n \n \n  \n \n  Roll Call \nDr. Keipp Talbot, ACIP Chair , conducted a roll call, which established that a quorum was \npresent. A list of Members, Ex Officios, and Liaison Representatives is included in the \nappendixes at the end of this summary document. The following COI was identified: Dr. \nMald onado is the Stanford Principal Investigator (PI) for the COVID vaccine trials. \nAGENCY UPDATES \nCenters for Disease Control and Prevention \nDemetre Daskalakis, MD, MPH highlighted CDC’s activities in seasonal respiratory viruses , with \nthe commercialization of the COVID -19 vaccine, launch of multiple RSV products, and the \nagency’s staple work in seasonal influenza. While the times have been exciting, there also have \nbeen some significant challenges and important issues that continue to need to be addressed. \nAs of May 11, 2024, 22.5% of adults ≥18 years of age and 14 .4% of children 6 months to 17 \nyears of age were reportedly up to date with the 2023-2024 COVID -19 vaccine . Vaccination \ncoverage increased by age and was highest among adults , with receipt of at least 1 updated \n2023-2024 COVID -19 vaccine reaching 41.5% among adults ≥ 75 years. The Bridge Access \nProgram, launched in Fall 2023, provides no-cost COVID-19 vaccines to adults without health \ninsurance and adults whose insurance does not cover all COVID -19 vaccine costs. \nApproximately 1.5 million doses have been provided through this program from September \n2023 through May 2024. This temporary program will end in August 2024. \nThere are other respiratory viruses that continue to be t he focus of attention at CDC, including \navian influenza A(H5N1) . CDC’s current A(H5N1) bird influenza human health risk assessment \nfor the general public remains low. CDC continues to respond to the public health challenge \nposed by a multistate outbreak of avian influenza A(H5N1) virus in dairy cows and other animals \nin the US. T o date, there have been 3 human cases in the US associated with an ongoing \nmultistate outbreak of A(H5N1) in dairy cows. All 3 cases were mild, and all had direct contact \nwith infected cows. CDC is working in collaboration with the US Department of Agriculture (USDA), FDA, state public health and animal health officials, and other partners using a One Health approach to continue to monitor the impact on public health. \nMeasles represents another ongoing public health threat. As of June 6, 2024, a total of 151 \nmeasles cases were reported by 22 jurisdictions in the US in 2024. This is in comparison to \n2023, during which a total of 58 measles cases were reported by 20 jurisdictions. Jurisdictions \nat highest risk for measles continue to be those containing communities with persistently low vaccination coverage and importations from locations with measles outbreaks. \nIn terms of Mpox, a report in a May MMWR showed that infection after receipt of 2 JYNNEOS \ndoses is estimated to have occurred in <1% of fully vaccinated persons and comprises a small \nproportion of national cases. Among persons who experienced infection after having received a complete 2-dose series and for whom complete data were available, infections have been milder than those among unvaccinated persons. Disparate time intervals from vaccination to infection among fully vaccinated persons suggest that immunity is not waning. \n16 \n \n  \n \n    \n \n \n  \n  \n  \n \n \n    \n  \n  \n    \n \n   \n \n \n \n  \n  \n   \n    \n    \n     \n   \n    \n \n \n \n    \n    \n   \n     \n \n \n \n \n  \n    \n \n \n \n \n   Regarding anthrax , Emergent BioSolutions Inc. announced in July 2023 that FDA had approved \nCYFENDUS or Anthrax Vaccine Adsorbed, Adjuvanted, for post-exposure prophylaxis of \ndisease following suspected or confirmed exposure to Bacillus anthracis in persons 18─ 65 \nyears of age when administered in conjunction with recommended antibacterial drugs. This \nvaccine is comprised of the previously FDA -approved Anthrax Vaccine Adsorbed (AVA) and an \nadditional adjuvant, CpG7909. It has been demonstrated that by using an additional adjuvant, 2 \ndoses administered over 14 days elicit protective levels of immune response, as opposed to 3 doses over 4 weeks required for AVA to illicit an adequate immune response. AVA Adjuvanted \nvaccine is currently a component of the US government’s (USG’s ) Strategic National Stockpile \n(SNS) for use in an anthrax public health emergency and will replace AVA as it expires. ACIP \nwill soon convene an Anthrax WG to review data and provide recommendations for its use to the ACIP committee. \nThough not necessarily thought of as vaccine-preventable, antimicrobial resistance (AMR) is \nanother important topic . In September 2024, the USG will have an opportunity to demonstrate \nUS leadership in combatting AR at the second United Nations General Assembly High-L evel \nMeeting on Antimicrobial Resistance 2024. The USG has set ambitious goals to reduce \nhealthcare-associated infections (HAIs), including those caused by antimicrobial -resistant \ngerms, and protect patients and healthcare personnel (HCP) . \nCenters for Medicare and Medicaid Services \nMary Beth Hance reported that in February 2024, CMS released an updated Coverage and \nPayment of Vaccines and Vaccine Administration Under Medicaid, the Children’s Health \nInsurance Program, and Basic Health Program .\n1 She amplified that CMS continues to share \nwith all of its partners and stakeholders to highlight coverage of vaccines and amplify activities \nthat are being undertaken by Medicaid agencies and other partners throughout the country to \nreally encourage uptake of vaccines and increase vaccination, particularly for pediatric \nvaccines.  CMS will continue to look for these opportunities to amplify this and emphasize \ncoverage of vaccines throughout the Medicaid, Medicare, and Marketplace. \nFood and Drug Administration Dr. David Kaslow, FDA, reported that since the last FDA agency report during the February \n2024 ACIP meeting and that a propos to this convening of ACIP, FDA’s Vaccines and R elated \nBiologics Products Advisory Committee (VRBPAC) convened twice and the Office of Vaccines \nResearch and Review (OVRR) took several major regulatory actions , of which Dr. Kaslow briefly \nhighlighted 3 actions. In March, VRBPAC met in open session to discuss and make recommendations on the \nselection of strains to be included in the influenza virus vaccines for the 2024 to 2025 influenza \nseason in the Northern Hemisphere. Having discussed the need to transition from quadrivalent to trivalent influenza vaccines at several previous VRBPAC meetings, committee members generally agreed on transitioning to trivalent influenza vaccines only, for use in the US starting in the 2024- 2025 respiratory virus season, and US -licensed quadrivalent vaccines for ex -US \ndistribution purposes only. There also was general agreement among VRBPAC members for \nchanging the H3 components but maintaining the currently recommended H1 and B components. \n1 https://www.medicaid.gov/medicaid/quality-of-care/downloads/vacines-coverage-payment.pdf \n17 \n \n    \n \n    \n \n  \n  \n    \n \n      \n   \n     \n \n \n \n     \n    \n \n   \n \n \n   \n   \n \n   \n \n \n  \n \n \n  \n \n   \n  \n \n  \n \n   \n   VRBPAC again met in open session in June to discuss and make recommendations on the \nselection of the 2024-2025 formula for COVID -19 vaccines for use in the US beginning in Fall \n2024. VRBPAC unanimously voted to recommend a monovalent JN.1-lineage vaccine composition and discussed considerations for the selection of a specific strain, be it JN.1 or \nKP.2. Subsequently, FDA communicated advice to manufacturers of licensed and authorized \nCOVID -19 vaccines on use of these 2 specific strains for the 2024-2025 For mula. \nIn terms of 3 major regulatory actions taken since February , on June 7, RSV Vaccine, \nAdjuvanted was approved for active immunization for the prevention of l ower respiratory tract \ndisease (LRTD ) caused by RSV in individuals 50 through 59 years of age who are at increased \nrisk for LRTD caused by RSV. On June 17, pneumococcal 21-valent conjugate vaccine was \napproved for active immunization for the prevention of invasive disease caused by 22 \nStreptococcus pneumoniae serotypes in individuals ≥18 years of age and was approved under \naccelerated approval for active immunization for the prevention of pneumonia caused by Streptococcus pneumoniae serotypes in individuals ≥18 years of age. \nHealth Resources and Services Administration \nCDR Reed Grimes, MD, MPH provided a Health Resources and Services Administration \n(HRSA) update on 3 important vaccination efforts that HRSA undertakes to support the n ation’s \npublic health. First, HRSA’s Health Center Program is a cornerstone of the country’s health care \nsystem, providing affordable, high-quality, comprehensive primary care services to more than \n30 million medically underserved people nationwide, especially for individuals and families who are uninsured; enrolled in Medicaid; living in rural, remote, or underserved areas; struggling to \nafford their health insurance co-pays; experiencing homelessness; residing in public housing; or \notherwise finding it hard to find a doctor or pay for the cost of care. Today, the nearly 1,400 HRSA -funded health centers operate more than 15,000 health care sites, as well as mobile \nclinics, community outreach events to engage patients in accessible settings, and other satellite sites. HRSA’s Health Center Program has been essential in vaccine uptake for COVID -19 \nvaccine doses. As of April 2024, more than 24 million vaccine doses have been administered by \nall health centers , with 70 % to racial and/or ethnic minority patients. \nSecond, the Countermeasures Injury Compensation Program (CICP) continues to make \nunprecedented progress in reviewing claims alleging injuries from medical countermeasures (e.g., Mpox vaccine, anthrax vaccine, COVID -19 vaccine) deployed in response to pandemic, \nepidemic, and security threats. As of June 1, 2024, CICP has specifically rendered decisions on 2,814 COVID -19 claims and continues to work through the backlog of claims filed following the \nextraordinary deployment and administration of over 676 million COVID -19 vaccines in \nresponse to the pandemic. More information about the CICP can be found on the website.\n2 \nThird, the National Vaccine Injury Compensation Program (VICP) continues to actively process claims. In FY 2024, as of June 1, 2024, petitioners have filed 783 VICP claims, nearly $119 million was awarded to petitioners, and over $34 million was awarded to pay attorney’s fees and costs. In addition, the VICP has approximately 600 claims alleging vaccine injury awaiting \nactivation for review. More data about the VICP can be obtained on its website.\n3 \n2 https://www.hrsa.gov/cicp \n3 https://www.hrsa.gov/vaccine-compensation/data/index.html \n18 \n \n  \n \n   \n   \n   \n \n \n \n \n \n    \n  \n  \n   \n \n \n \n \n \n \n   \n    \n \n  \n \n  \n \n  \n \n   \n \n \n  Indian Health Services \nMatthew Clark, MD, FAAP, FACP emphasized that the Indian Health Service (IHS) continues to \nprioritize vaccination as its number one clinical and public health prevention priority. As part of \nIHS’s ongoing national E3 vaccine strategy, they offer every patient at every encounter every \nACIP -recommended vaccine, when appropriate. To date, they have designated 29 E3 \nChampion Pilot sites in 9 IHS Areas. In the past several months, utilizing a grassroots approach, \nthe pilot sites have shared and IHS has disseminated innovative strategies to promote vaccine \nacceptance and improve vaccine coverage rates in T ribal communities. \nUnder the leadership of IHS Chief Medical Officer, Dr. Loretta Christensen, last month as recently recognized by partners at CMS , IHS announced its E3 Champions Pilot Community \nDevelopment Project to cross -pollinate the IHS system of care with multidisciplinary best \npractices. IHS has recently designated 3 IHS E3 Champions including one federal, one tribal, \nand one urban site in 3 IHS Areas who have demonstrated excellence by exceeding established \nthresholds to improve vaccine coverage rates for AI/AN people. Dr. Clark drew particular \nattention to the outstanding work of one of these IHS E3 Champions , its Tribal partners in the \nYK Delta region of Alaska. \nThe YK region is a landmass roughly equivalent in size to the State of Oregon and larger than \nhalf of the states in the country. Serving a population of 23,000 Indigenous people in 58 remote \ntribal communities off the road system, the YK Delta historically has the highest rate of severe RSV disease in the US and arguably in the world. \nDuring the 2023-2024 respiratory viral season, with support from the V FC program and a \nsupplemental allocation from IHS, the Yukon Kuskokwim Health Corporation (YKHC) vaccine \nteam conducted regular bush-plane flights to remote tribal villages, sometimes up to 3 villages a \nday, to administer nirsevimab and other recommended vaccines to eligible infants and toddlers, \nwith a vaccine acceptance rate of over 60%. In addition, among newborn infants born in the YK Delta region during this first season of availability, immunization with nirsevimab approached \n100% with an obstetric delivery rate of roughly 30 to 35 newborns per month. Notably, \npreliminary data analysis, pending publication, indicates that no single infant in the YK Delta \nregion who had been effectively immunized with nirsevimab experienced severe disease, including hospitalization. Indicative of a virtuous cycle resulting from proactive efforts to promote RSV protection among this high-risk service population, IHS’s tribal partners at YKHC also \nmanaged to raise baseline composite immunization rates among infants ages birth to 1 year by \nover 10% for all ACIP -recommended vaccines. Working in collaboration with immunization \nexemplars like their tribal partners in the YK Delta region of Alaska, the IHS will continue to \nmitigate the risk of vaccine preventable illness in Indian Country. \n19 \n \n  \n \n    \n \n \n     \n     \n \n \n  \n \n  \n \n   \n   \n  \n  \n    \n \n \n   \n  \n   \n    \n  \n   \n  \n     \n  \n    \n  \n     \n  \n \n \n \n       \n  \n      \n  \n      \n   \n \n       \n \n \n \n \n   \n   \n \n  National Institutes of Health \nDr. John Beigel, NIAID, NIH, provided several updates for the National Institutes of Health \n(NIH). NIH continues to support multiple areas of vaccine research for multiple pathogens, a few \nof which he highlighted that he thought would be of interest to the ACIP. In response to the \nhuman and bovine A(H 5N1) cases , the NIH released an A (H5N1) influenza research agenda \nthat describes NIH’s ongoing and planned efforts to meet 4 key objectives : 1) increasing \nunderstanding of the biology of H5N1 viruses and the factors that influence their ability to \ntransmit and cause disease; 2) developing and evaluating prevention strategies, such as \nvaccines; 3) advancing existing and novel treatments, including antivirals and monoclonal \nantibodies; and 4) supporting strategies for detecting H5N1 virus. The agenda can be found on \nthe NIH website and will be provided in NIH’s written updates.4 \nRegarding Ebola and NIH’s continuing efforts to advance vaccines for pandemic and \npreparedness , scientist at the Vaccine Research Center (VRC) evaluated a heterologous prime -\nboost strategy for Ebola. This was done in a Phase 1 trial in the US and in Uganda. The \nstrategy uses a ChAd3-EBO-Z with an MVA boost, The heterologous prime-boost regimen was \nwell-tolerated and induced a robust immune response, which persisted up to a year. The results \nwere published in n pj vaccines .5 \nFor malaria, the NIH published interim trial results showing an injected dose of an experimental \nmalaria monoclonal antibody was 77% effective at preventing disease in children in Mali during \nthe country's 6-month malaria season. M onoclonals are seen as a possible component to \nminimize morbidity and mortality from malaria. In efforts toward an HIV vaccine, there have \nbeen some important advances in the development of broadly neutralizing antibodies. A class of \nbroadly neutralizing antibodies called 10E8 is a priority for HIV vaccine development because \nthey can bind to conserved regions in glycoprotein Gp41. \nThis has been difficult to advance previously . Germline targeting is an approach that guides \nnaïve B cells to develop into B cells that can produce these broadly neutralizing antibodies . \nRecently , a scientist described an approach to germline targeting that was done in mice that \ndevelop broadly neutralizing antibodies to this Gp41. The findings published in N ature \nImmunology are encouraging.6 It is an incremental step, but an incremental and important step \nin developing a preventive HIV vaccine. \nOffice of Infectious Disease and HIV/AIDS Policy \nDr. Chinedu Okeke, O ffice of I nfectious Disease and HIV/AIDS Policy (OIDP), report ed that the \nNational Vaccine Advisory Committee (NVAC) met on June 12-13, 2024. During this meeting, \nAdmiral Rachel Levine, the Assistant Secretary for Health at HHS, charged the committee with \nproviding guidance and recommendations to support the development of the next 5-year \nNational Vaccine Strategic Plan (NVSP). This plan provides a vision for the nation and helps to \nensure continued responsiveness to an evolving vaccine and immunization landscape. \nThe next NVAC meeting will take place on September 12-13, 2024, in-person and as a live \nwebcast. The meeting will be made available on the meeting page later this summer on \nhhs.gov . \n4 https://www.nih.gov/news-events/news-releases/nih-releases-h5n1-influenza-research-agenda \n5 https://www.nature.com/articles/s41541-024-00833-z#citeas \n6 https://www.nih.gov/news-events/news-releases/novel- vaccine -concept-generates-immune-responses-could-produce-multiple-\ntypes-hiv-broadly-neutralizing-antibodies \n20 \n \n    \n      \n \n  \n  \n  \n   \n \n   \n  \n  \n  \n   \n   \n \n \n \n     \n \n  \n  \n  \n   \n \n \n  \n \n  \n  \n \n  \n \n     \n \n    \n  \n  \n  \n   \n \n \n \n In terms of planning for the next iteration of the NVSP 2026─ 2030 updates , the OIDP , in \ncollaboration with the HHS Interagency Vaccine Work G roup (IVWG) has started planning data \ngathering and engagement efforts for the next iteration of the NVSP for the 2026─ 2030. The \nNVAC report and its recommendation is a process which will form an inclusive and robust \nconsultation process that will include listening sessions with stakeholders and other inputs. They \nare putting together a request for information to be released very soon. ACIP members were \nencouraged to actively submit feedback and recommendations during this process . \nIn terms of responding to the Senate Appropriation Committee, OIDP prepared a report that just \nwent into official clearance in response to the request from the Senate Appropriation Committee \nthat encouraged the OASH, in partnership with CDC , to lead the development of a government-\nwide coordinated effort to ensure the implementation of the ACIP’s recommendation that all \nadults between 19 and 59 years of age be vaccinated for Hepatitis B. The Senate Appropriation \nCommittee requested this report be prepared before the end of fiscal year 2024. \nPRESENTATIONS \nThe COVID -19 vaccine session began with an update from the ACIP COVID-19 Vaccines Work \nGroup by Dr. Matthew Daley, Work Group Chair.  He reminded the committee of the 2023-2024 \nCOVID -19 vaccine recommendations, which in September 2024 were recommended as \nauthorized under EUA or approved by BLA for persons ≥6 months of age.  In February 2024, \nACIP recommended that adults 65 year and older receive an additional dose of 2023- 2024 \nCOVID -19 vaccine. At that meeting, the committee discussed next steps for the COVID-19 \nvaccine program, including shifting to a vote at the June ACIP meeting for future vaccine \nupdates. \nThe work group had started their discussions with considerations for an age-based versus a \nrisk-based recommendation.  The work group consensus was to proceed with deliberations for an age-based recommendation for everyone ages ≥6 months for the 2024-2025 season. \nOn June 5, 2024, FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) met to discuss strain selection for 2024-2025 COVID-19 vaccines.  Based on the totality of the evidence presented, FDA advised manufacturers to develop monovalent JN.1 lineage COVID -19 vaccines, with a preference for the KP.2 strain, if feasible. \nDr. Fiona Havers, CORVD, CDC, presented an update on COVID -19 hospitalizations from \nCOVID -NET, a population-based surveillance system that collects data from more than 300 \nacute care hospitals in 98 counties across 13 states. Racial and ethnic disparities in COVID -19 \nhospitalizations persist, with the highest hospitalization rates among non-Hispanic American \nIndian and Alaska Native persons . From October 2023 through May 2024, adults ages 65 years \nand older comprised 67% of all COVID -19 hospitalizations captured in COVID -NET, with adults \n75 years and older comprising almost half of all COVID 19 hospitalizations. Children and \nadolescents ages 17 years and younger comprised 4% of all COVID -19-associated \nhospitalizations . Infants <6 months had recent cumulative hospitalization rates that are \napproximately 6 times that of hospitalization rates in children ages 6 months to 4 years, the pediatric age group with the second highest rates. Overall, 50% of hospitalized infants, \nchildren, and adolescents ages have no underlying medical conditions, but the prevalence of underlying medical conditions in children hospitalized with COVID -19 increases with increasing \nage. \n21 \n \n    \n \n   \n \n  \n \n \n  \n \n \n  \n \n \n  \n \n  \n  \n  \n \n   \n \n \n \n \n \n \n \n \n \n  \n \n  \n  \n   \n  \n \n \n The majority of hospitalized children <2 years have no underlying medical conditions . Only 5% \nof children and adolescents hospitalized with COVID -19 received the 2023– 2024 vaccine dose, \nthe most recent available, prior to hospitalization, and the vast majority of hospitalized children \nhad not received the vaccine available in fall 2023 or in the preceding year. Only 11% of \nCOVID -19-associated hospitalizations among adults ages 18 years and older received a 2023– \n2024 vaccine dose and the majority had not received any COVID -19 vaccine after August 2022.  \nAmong adults, underlying conditions increase risk for hospitalization, but age remains strongly associated with risk for hospitalization. \nDr. Ruth Link -Gelles, CORVD, CDC, presented an update on the effectiveness of 2023-2024 \nCOVID -19 vaccines.  2023-COVID -19 vaccination provided increased protection against \nsymptomatic SARS -CoV -2 infection and COVID -19-associated ED/UC visits and \nhospitalizations compared to no 2023-2024 vaccine dose. Waning patterns appeared similar to \nprevious COVID -19 vaccine formulations; the most durable protection appeared to be for critical \nillness, though statistical power was lacking in the longest time period since vaccination.  As \nwith previous COVID -19 vaccine formulations, effectiveness was similar across age groups.  \nReceipt of 2023-2024 COVID -19 vaccine provided protection against JN.1 and other circulating \nvariants, though may be lower than protection provided against XBB sublineage variants . \nDr. Jonathan Duffy, Immunization Safety Office, Division of Healthcare Quality Promotion \n(DHQP) , CDC, presented an update on COVID -19 vaccine safety surveillance for the 2023-\n2024 season.  The Vaccine Safety Datalink (VSD) identified two statistical signals for mRNA COVID -19 vaccines during the 2023 -2024 season.  There was a statistical signal for Guillain -\nBarré syndrome (GBS) following Pfizer COVID -19 vaccine among people aged ≥65 years . No \nassociation between mRNA COVID -19 vaccines and GBS had been observed prior to this \nseason in VSD or other systems.  The increased rate ratio observed during the 2023-2024 season may or may not represent a true risk; if there is a true risk, it is estimated to be similar to what is considered acceptable for other adult vaccines.  There also was a statistical signal for ischemic stroke following Moderna (aged ≥65 years) and Pfizer (aged 50-64 years) COVID -19 \nvaccines.  The VSD previously observed a statistical signal for ischemic stroke during 2022-2023 for bivalent Pfizer COVID-19 vaccine (aged ≥65 years) . Available data do not provide \nclear and consistent evidence of a safety problem for ischemic stroke with mRNA COVID -19 \nvaccines.  No other new or unexpected safety concerns were identified for the 2023-2024 COVID -19 vaccines ; any real or theoretical risks of vaccine adverse events need to be placed in \nthe context of the benefits of COVID -19 vaccines in preventing COVID-19 and its potentially \nserious complications . \nDr. Lisa Prosser, University of Michigan (UM) , presented an economic analysis of COVID -19 \nvaccination.  According to the model developed by the UM team, COVID -19 vaccination averts \nmorbidity and mortality in all age groups, but with substantial variation in impact by age.  In adult \nage groups, the current model projects somewhat less favorable results overall due to declining \nburden of illness.  ICERs for vaccination in the 65 years+ age group ($23,000 per QALY) are robust to changes in parameter inputs across plausible ranges (cost saving to $117,000 per QALY).  ICERs for vaccination of 18- 49 year old ($212,000 per QALY) and 50-64 year old \n($113,000 per QALY) age groups are sensitive to changes in parameter inputs, including vaccine cost.  In pediatric age groups, ICERs for vaccination of 5-11 year old ($200,000 per \nQALY) and 12-17 year old ($203,000 per QALY) age groups are very sensitive to changes in \nparameter inputs.  The evidence base of pediatric age groups overall is less robust, and the estimated results reflect a higher degree of uncertainty compared with adult age groups. \n22 \n \n  \n \n   \n    \n   \n  \n     \n \n  \n  \n  \n   \n \n      \n \n  \n \n  \n \n \n   \n \n \n \n \n  \n \n \n  \n \n    \n  \n   \n \n \n \n \n   \n \n  Dr. Lakshmi Panagiot akopoulos presented the EtR Framework for 2024 -2025 COVID-19 \nvaccines in persons ≥6 months of age.  ≥ The work group interpretation was that COVID -19 \ncontinued to be a public health problem, with COVID -19 COVID-19-associated hospitalizations \nand deaths occur ring all year round, but peak ing in December – February .  COVID-19 -\nassociated hospitalizations and deaths are highest in adults aged 75 and older.  Among children \nhospitalized for COVID -19, 50% had no underlying medical conditions; of those, 18% were \nadmitted to the ICU.  Racial and ethnic differences in COVID -19 hospitalization rates persist. \nThe work group concluded that the balance between desirable and undesirable effects favored the intervention (2024-2025 COVID -19 vaccine). The 2023-2024 COVID -19 vaccine wa s \neffective in preventing ED/UC visits and preventing severe outcomes related to COVID -19 (e.g., \nhospitalization or death).  COVID -19 vaccines continue to have a favorable safety profile as \nemonstrated by robust safety surveillance over 3 years of COVID -19 vaccine use.  The \nstatistical signals observed in the VSD (ischemic stroke and GBS) are not clear or consistent, \nand are seen in the age groups (adults ≥ 50 years and adults ≥ 65 years, respectively) with the \nhighest burden of disease that would benefit the most from updated COVID -19 vaccination.  \nModeling projects more hospitalizations averted when 2024-2025 COVID -19 vaccines \nare universally recommended compared to no recommendation or recommended only for those \nat high risk . \nFor the values domain of the EtR, the work group thought that people recommended to receive 2024-2025 COVID -19 would have variable assessments of whether or not the benefits \noutweighed the risks of vaccination. Approximately 30% of parents of children ages 6 months – \n17 years reported concern about their child getting COVID -19, but confidence in COVID -19 \nvaccine safety and vaccine importance was highest among parents of adolescents.  Adults ages 65 years and older were more concerned about COVID -19 disease and had higher confidence \nin vaccine safety and vaccine importance than those <65 years.  Racial and ethnic minority groups, older adults, and those with lower incomes are more concerned about getting COVID -19 than other groups . \nFor the acceptability domain, the work group thought that acceptability of the intervention would \nbe variable.  Vaccine coverage with at least 1 dose of 2023-2024 COVID -19 vaccine was \napproximately 20% in adults aged ≥ 18 years . From August 2021 to February 2024, the \npercentage of adults who report being up to date with COVID -19 vaccination has decreased \nfrom 69% to 28%.  Concern about side effects is the most likely reason for not being vaccinated.  \nLess than 30% of people report having received a healthcare provider recommendation for the \n2023-2024 COVID -19 vaccine.  COVID -19 vaccine coverage varies by age, race and ethnicity, \nmetropolitan statistical area, insurance status and household income. \nThe work group judged that implementation was probably feasible or that feasibility was \nvariable.  The 2024 – 2025 COVID -19 vaccine will continue to consist of single dose vial \npresentations and smaller minimum order quantities and storage and handling requirements are \nunchanged.  The increasingly complex routine vaccination schedule, which includes \nimmunizations for three seasonal viral respiratory diseases, presents potential barriers to implementation such as limited storage space due to more vaccines, more opportunities for vaccine administration errors and the need for increased education among vaccine providers.  \nVaccines will continue to be accessible; however, the end of the temporary Bridge Access \nProgram will result in decreased vaccine access for underserved populations . \n23 \n \n    \n  \n \n  \n  \n \n \n \n \n   \n  \n \n \n \n \n    \n     \n \n \n  \n   \n \n   \n \n   \n    \n  \n \n \n \n  \n  \n  \n  \n   The work group felt that 2024-2024 COVID -19 probably was a reasonable and efficient \nallocation of resources, or that it was variable. Base case ICERs ranged from $23,308 per \nQALY in adults aged ≥65 years to $212,225 per QALY in adults aged 18 -49 years.  Cost-\neffectiveness estimates in those ages ≥65 years were robust to input changes across plausible \nranges .  Cost -effectiveness estimates in those 5-17 years and 18-64 years were sensitive to \nchanges in inputs .  COVID-19 vaccination is most cost-effective in older adults in which disease \nburden is highest compared to younger adults ; COVID -19 vaccination is likely more cost-\neffective in populations with risk factors, such as underlying conditions, which increase their probability of hospitalization due to COVID -19.  ICERs would be more favorable in younger age \ngroups if the cost of vaccination was lower . \nBased on the evidence reviewed the work group judged that 2024-2025 COVID -19 vaccine \nshould be recommended.  The work group acknowledged that the benefits of COVID -19 \nvaccination vary by age and risk status.  Under a universal recommendation, 2024-2025 \nCOVID -19 vaccines will be available to all persons ages ≥6 months . Additional implementation \nefforts should be targeted toward those that will receive the most benefit from COVID -19 \nvaccination, including people ≥65 years old, people with underlying conditions including immunocompromise, and pregnant people to protect themselves and their infants.  The Work \nGroup will continue to evaluate COVID -19 vaccine policy, including the need for a \nuniversal recommendation, particularly as COVID-19 epidemiology continues to change. The \nwork group’s proposed vote was to recommend 2024-2025 COVID -19 vaccines as authorized \nor approved by FDA in persons ≥6 months of age.  Dr. Daley moved to approve the proposed \nvote language, and the motion was seconded by Dr. Brooks. \nDr. Jamie Loehr, Chair of the ACIP Influenza Vaccine Work Group, introduced the influenza \nsession. Dr. Vivien Dugan, Influenza Division, CDC, provided an update on influenza A(H5N1). \nHighly pathogenic avian influenza A H5N1 [ HPAI A(H5N1) ] was detected in birds in 1996.  \nSporadic HPAI A(H5N1) virus infections of mammals have been reported since 2003-2004.  A(H5N1) clade 2.3.4.4b viruses  emerged in wild birds in 2020 and 29 human cases of HPAI \nA(H5N1) have been detected globally since January 2022, of which 4 were in the United States.  \nUSDA has confirmed A(H5N1) virus infections of dairy herds in >100 farms across 12 states , \nwith clade 2.3.4.4b virus and high levels of virus in raw milk.  Infection of other animal species \n(wild birds, cats, racoon, opossums ) have been reported in association with infected dairy herds \nin the United States . Since April, a number of human cases have been reported among adults \nworking at dairy farms and in contact with cows. None had severe illness and no human-to-\nhuman transmission has been detected. Available candidate vaccine viruses are expected to \nprovide good protection against this virus.  Overall the risk to the public remains low, but there is \nincreased risk with exposure to infected animals or environment (occupational, recreational).  \nExposed individuals should monitor for symptoms after first exposure and for 10 days after last exposure. \nDr. Lisa Grohskopf presented updates, work group considerations, and proposed \nrecommendations for the 2024-25 influenza season.  All influenza vaccines marketed in the United States for the 2024-25 season will be trivalent; there will be no influenza B/Yamagata component, following no confirmed detections of wild-type influenza B/Yamagata viruses since March 2020.  U.S. influenza vaccine composition for 2024-25 includes an update to the \ninfluenza A(H3N2) component: an A/Victoria/4897/2022 (H1N1)pdm09- like v irus for egg-based \nvaccines or an A/Wisconsin/67/2022 (H1N1)pdm09-like virus for cell and recombinant vaccines; \nan A/Thailand/8/2022 (H3N2) -like virus for egg- based vaccines or an A/Massachusetts/18/2022 \n(H3N2) -like virus for cell and recombinant vaccines; a B/Austria/1359417/2021 (B/Victoria \nlineage) -like virus . \n24 \n \n   \n \n \n  \n    \n \n \n \n  \n \n \n  \n \n  \n    \n \n  \n \n \n \n    \n \n \n \n   \n  \n \n \n  \n  \n   \n \n \n    \n  \n \n \n For the 2023-2024 influenza season, ~158 million doses of influenza vaccine distributed in \nUnited States.  No new safety concerns were identified for influenza vaccines . \nOn behalf of the work group, Dr. Grohskopf summarized evidence on use of higher dose and \nadjuvanted influenza vaccines for solid organ transplant (SOT) recipients. More than 45,000 \nsolid organ transplants were performed in the U.S. in 2023. American Society for \nTransplantation (AST) states that high-dose or boosted dosing might be preferable post-\ntransplant, but ACIP has recommended that SOT recipients should receive an age-appropriate \ninactivated or recombinant influenza vaccine (i.e., an IIV or RIV).  An evidence review was \nundertaken for use of high -dose inactivated, adjuvanted inactivated, and/or recombinant \ninfluenza vaccines as an option for influenza vaccination of solid organ transplant recipients who are younger than the approved age indication (i.e., <65 years for high-dose and adjuvanted \ninfluenza vaccines, and <18 years for recombinant influenza vaccine). The work group judged \nthat influenza in SOT recipients is a public health problem; manifestations of influenza can be more severe in this population.  For benefits and harms, the work group felt that desirable \neffects outweighed undesirable effects, favoring the intervention.  The domains of values , \nacceptability , resource use, and feasibility were supportive of the intervention (“probably yes”) \nand the work group felt that the intervention would probably increase health equity, leading to a \nproposed recommendation that all persons should receive an age-appropriate influenza vaccine \n(i.e., one approved for their age), with the following exception: solid organ transplant recipients \naged 18 through 64 years on immunosuppressive medication regimens may receive either  HD -\nIIV3 or aIIV3 as an acceptable option (without a preference over other age-appropriate IIV3s or RIV3). Additionally , the work group proposed that ACIP reaffirm the recommendation for \nroutine annual influenza vaccination of all persons aged ≥6 months who do not have \ncontraindications .  Dr. Kotton made a motion to reaffirm the recommendation for annual \ninfluenza vaccination and this was seconded by Dr. Daley.  Dr. Kotton made a motion for use of \nHD-IIV3 or aIIV3 as an acceptable option in SOT recipients aged 18 through 64 years and Dr. Loehr seconded the motion. \nThe pneumococcal vaccines session opened with an update from the ACIP Pneumococcal \nVaccine Work Group Chair, Dr. Jamie Loehr, who reminded the committee that during the \nCOVID -19 pandemic, invasive pneumococcal disease (IPD) rates reached a historically low \nlevel in all age groups.  During 2021-2023, new pneumococcal conjugate vaccines PCV15 and \nPCV20 were recommended for both adults and children.  A 21 -valent pneumococcal conjugate \nvaccine (CAPVAXIVE™, Merck) containing 8 serotypes not in other pneumococcal vaccines \nwas approved by the FDA for adults aged ≥ 18 years on June 17, 2024. Additional higher -\nvalence pneumococcal conjugate vaccines are currently in clinical development.  PCV21 includes serotypes accounting for 81% of IPD cases in 19-64 year olds with a risk -based \nindication for pneumococcal vaccine and 85% of cases among those ≥65 years, compared with 58% and 54%, respectively, for PCV20. An increase in serotype 4 (included in PCV 15 and \nPCV20 vaccines, but not in PCV21) has been seen in certain subpopulations (e.g., adults \nexperiencing homelessness, especially in the western U.S., and adults in Alaska, especially Alaska Native adults).  The following groups are currently recommended to receive a dose of pneumococcal conjugate vaccine (PCV): adults aged ≥65 years who have not received a PC V; \nadults aged 19– 64 years with certain underlying conditions or risk factors who have not received \na PCV ; and certain adults who have received PCV13 but have not received PCV20.  Among \nadults vaccine coverage is generally lower for risk -based recommendations compared with age-\nbased recommendations.  The work group is proposing that ACIP recommend PCV21 as an option for adults aged ≥ 19 years who currently have a recommendation to receive a dose of \nPCV. \n25 \n \n  \n   \n \n \n  \n   \n    \n     \n  \n    \n   \n \n \n \n \n \n  \n \n \n \n \n \n \n   \n \n  \n  \n \n \n  \n \n \n \n \n  \n Dr. Charles Stoecker, Tulane University School of Public Health and Tropical Medicine, \npresented an economic assessment of PCV21 in U.S. adults . Based on the models presented, \nreplacing PCV20 with PCV21 at age 65 increases QALYs with modest increases in cost.  Simulations range from $4,000 to $28,000 per QALY in several scenarios.  Replacing PCV20 \nwith PCV21 is results in lower QALYs and more costs in a scenario where serotype 4 disease accounts for 30% of pneumococcal disease.  Replacing PCV20 with PCV21 at diagnosis of IC or CMC before age 65 is cost-saving .  Cost is $110,000 per QALY in a scenario where serotype \n4 disease accounts for 30%.  At serotype 4 disease proportions of 35% or above it results in \ndecreased QALYs .  Moving PCV21 vaccination from age 65 to age 50 increases case counts \nand deaths, but also results in gains in QALYs.  Disease burden is shifted from younger adults to older adults who have lower background QALY values.  Vaccinating at both age 50 and age 65 costs $300,000 per QALY , with sensitivity analyses range from $200,000 per QALY to \n$400,000 per QALY .  Vaccinating with PCV21 at age 19 instead of age 50 results in less health \n(both lower QALYs and more cases) and increased costs.  Supplemental PCV21 at age 65 that includes all adults that previously had PCV20 (at age 65 or at CMC/IC) costs $400,000/QALY; if \nthe supplemental dose  is delayed until age 70 the cost drops to $300,000/QALY.  Supplemental PCV21 for the CMC/IC population ranges from $200,000 to $300,000 per QALY in the base case.  Cost per QALY is 5-30% lower if PCV21 is delayed 5 years after PCV20 \nvaccination rather than 1 year afterward.  Assuming no herd immunity from childhood PCV20 \nprogram is associated with the lowest cost per QALY . \nDr. Andrew Leidner, Immunization Services Division, CDC, provided a summary of three economic analyses on the use of PCV21 among adults in the U.S.  The three models were the Tulane-CDC model; a model developed by Merck, the manufacturer of the PCV21, PCV15 and \nPPSV23 vaccines ; and a model from a team at the University of Pittsburgh.  As modeled, most \nstrategies improved health, although age-based vaccination at 19 years instead of 50 years in \nthe Tulane- CDC model did not improve health.  Several strategies were cost-saving, but there \nwas v ariability in estimates across models for age 50 and supplemental dose strategies . \nDr. Miwako Kobayashi, Division of Bacterial Diseases, CDC, presented the work group’s EtR \nand policy options for use of PCV21 in adults.  For the question of should PCV21 be \nrecommended for U.S. adults aged ≥19 years who currently have a recommendation to receive \na PCV, the work group felt that “desirable consequences clearly outweigh undesirable consequences in most settings ”.  For the question of should PCV21 be recommended for U.S. \nadults aged 50-64 years who currently do not have a risk -based pneumococc al vaccine \nindication, there was not a clear consensus of the work group.  Of the available options, “Desirable consequences probably outweigh undesirable consequences in most settings” was most frequently selected by WG members, but did not reach the majority. Some selected “Desirable consequences clearly outweigh undesirable consequences“ and “The balance between desirable and undesirable consequences is closely balanced or uncertain”, but few \nbelieved that undesirable consequences outweighed desirable c onsequences. For the third \npolicy question, should PCV21 be recommended for U.S. adults aged 19-49 years who currently \ndo not have a risk -based pneumococcal vaccine indication, the majority of WG members \nselected “undesirable consequences probably outweigh desirable consequences in most \nsettings.” \nFor the equity domain, Dr. Kobayashi presented data on invasive pneumococcal disease (IPD) \nby race/ethnicity.  Racial disparities in IPD incidence have long existed, but disparities due to \nPCV13-type IPD decreased after 2010, when PCV13 was introduced in the pediatric population.  \nMost of the remaining disparities are due to non-PCV13-type disease.  \n26 \n \n  \n   \n \n    \n \n \n  \n \n \n \n \n  \n  \n  \n \n \n \n  \n  \n \n \n \n \n \n \n      \n  \n    \n  \n \n  \n   \n \n \n  \n   \n \n \n  \n \n \n  \n In Black adults, IPD rates peak at a younger age at 55 to 59 years compared with non-Black \nadults who have a steady increase in IPD rates with increasing age; the IPD rates for Black \nadults 50 years and older exceeds the IPD rate for all adults 65 years and older. This is likely \ndue to multiple factors, but differences in prevalence of underlying medical conditions that \nincrease the risk of pneumococcal disease may be one contributing factor . Adults 19 -64 years \nwith a risk -based indication of pneumococcal vaccination have had lower vaccine coverage \ncompared with adults 65 years and older with an age-based vaccine recommendation, and disparity in vaccine coverage by race and ethnicity exists. Within adults 65 years and older, the \nproportion with receipt of any pneumococcal vaccine was significantly lower in Black and \nHispanic adults compared with white adults. \nAn increase in serotype 4 IPD cases has been reported in certain adult populations in recent \nyears.  Serotype 4 is contained in previous pneumococcal vaccines but not in PCV21.  Serotype \n4 IPD cases had nearly been eliminated after PCV7 use in children but IPD clusters have been \nreported in certain populations (e.g., people experiencing homelessness ). In certain areas, \nincrease in serotype 4 IPD cases observed in routine surveillance in recent years, especially post-2020, after near elimination; increases have been reported in the western United States \n(Alaska, Navajo Nation, Active Bacterial Core Surveillance site s in Colorado, New Mexico, and \nOregon).  Serotype 4 a ppears to primarily affect adults aged <65 years with risk -based \npneumococcal vaccine indications . \nIn summary, the work group agreed that available evidence supports PCV21 use for adults \ncurrently recommended to receive a PCV.  The work group could not reach a consensus on whether the age-based recommendation for PCV21 should be lowered from ≥65 years to ≥50 \nyears ; the work group did not support lowering the age-based recommendation for PCV21 to \nage 19 years.  The majority of work group members believed there was insufficient evidence to \nsupport lowering the age-based recommendation for currently recommended vaccines.  \nDr. Loehr shared his observations on the work group discussions.  The work group recognized \nthat lowering the age-based recommendation down to 50 years would result in a significant \nimprovement in equity but at significant cost. The duration of protection is a key variable that \nwould greatly impact the cost-effectiveness.  The work group also recognized that lowering the \nage down to age 50 for PCV21 but for other pneumococcal vaccines would be very confusing.  He stated that the work group welcomes the com mittee’s feedback and thoughts on these \nissues because the work group could not come to a consensus. \nDr. Talbot asked about data on coverage of ≥ 1 dose of any pneumococcal vaccine among \nadults 50-64 years of age with a risk -based indication and Dr. Kobayashi stated that the only \ndata she had been able to find was for PCV20, which is a relatively new vaccine and would not be helpful to address this question.  Dr. Talbot asked if the age-based recommendation were \nlowered to age 50, would it be for both PCV21 and PCV20.  Dr. Kobayashi replied that the work \ngroup was not supportive of lowering the age-based recommendation for other pneumococcal vaccines. Dr. Loehr asked what proportion of 50 -64 year olds are already included in the \ncurrent risk -based recommendation.  Dr. Kobayashi answered that it depends on the data \nsource, but ranges from 30 to 50 percent.  \nDr. Jamieson stated that she shares the concern about how confusing the recommendations \nare so she would not be on favor of lowering the age-based recommendation to age 50 years but would be supportive of recommending PCV21 as an option for adults currently recommended to receive a PCV.  \n27 \n \n   \n  \n   \n  \n \n   \n  \n \n \n  \n \n \n \n  \n \n  \n   \n \n \n \n \n \n  \n \n \n \n \n \n \n   \n \n  \n  \n \n \n    \n \n  \n \n \n    \n    \n  Dr. Daley expressed his appreciation for the conversation.  He stated that ACIP always has to \nmake recommendations with some uncertainty and that the economic analysis helped highlight \nthe critical issue of whether or not vaccination at age 50 would provide protection for longer than 15 years.  Clarity of policy leads to clarity of implementation and operationalization. Having \ndifferent recommendations for people 50 to 64 years of age with and without high-risk conditions \ncould not be implemented by primary health care providers.  He observed that vaccine recommendations do tend to settle over time as knowledge accumulates but is not sure that that is true in this case because of continued introduction of new vaccines.  With information about \nduration of protection, ACIP can make better decisions.  Dr. Daley stated that with the IPD \nburden in Black Americans 50 to 59 years of age being comparable to that in the overall \npopulation ≥65 years of age, the committee is missing something by not deciding.  He agreed \nwith the work group on not deciding on the age-based recommendation at this meeting but \nexpressed his hope that the committee could get there soon given the existing racial and ethnic \ndisparities in incidence of IPD. \nDr. Brooks stated his support for lowering the age-based recommendation down to age 50 \nyears.  Given the rates of IPD in the Black population 50-64 years of age, it would be very \nhelpful to have a universal recommendation.  Many are already included in the existing risk -\nbased recommendation but are not getting vaccinated.  \nDr. Kotton expressed concern about collateral damage on other vaccines .  Providers are \noverwhelmed by choices and changes and some people feel like they have had enough \nvaccines.  She pointed out some people would definitely benefit from pneumococcal vaccination at age 50 but not everyone; it would be great if persons at highest risk could be better targeted \nby vaccination programs.  She stated that she would prefer to focus efforts on vaccines for \nwhich there might be more benefit.  \nDr. Long stated that she thought that an age-based recommendation down to age 50 years \nwould decrease equity because lower risk people would be disproportionately vaccinated \ncompared to the populations at higher risk of IPD. The burden of disease data does not support \nlowering the age to 50 years for PCV20, so if only PCV21 were recommended, that would be a \npreferential recommendation and might impact the availability of PCV20.  C linical eff ectiveness \ndata are unavailable for either PCV20 or PCV21, and it’s unclear what’s going on with serotype 4. If PCV20 were no longer available, that could adversely impact other populations, and this is \na reason not to lower the age for PCV21. \nDr. Shaw asked about availability and supply for PCV21.  \nDr. Cineas stated that she favored an age-based recommendation from 50-64 years because of \nthe high prevalence of underlying conditions in this age group.  Implementation of risk -based \nrecommendations is difficult and she believed that an age-based recommendation would help \nreduce disparities.  \nDr. Loehr replied that the supply would come, but it takes a year for insurance companies to be \nrequired to cover a new vaccine recommendation.  Because PCV20 would still be used in \nchildren, he is less concerned about that vaccine not being available. He stated that he \nbelieved that an age-based recommendation down to age 50 would improve health equity.  \nDr. Matthew Clark, Ex Oficio member from the Indian Health Service, expressed support for \nPCV21 but that it was important that other vaccines remained available. Despite the availability \nof pneumococcal vaccines, t he burden of IPD remains 2 to 4 times higher among AI /AN adults \n28 \n \n    \n \n \n \n    \n   \n  \n      \n   \n \n  \n   \n   \n \n \n \n \n     \n   \n \n \n \n  \n       \n    \n \n \n \n   \n \n \n     \n  \n  \n  \n \n \n \n   \n   \n    \n  \n  \n \n  compared to the general U.S. population.  This is primarily due to serotypes not covered by \ncurrently available vaccines, but in the last few years, serotype 4 has emerged as a substantial \ncontributor to IPD in adults in Alaska and in the Navajo Nation, which are the two places in the \nU.S. with robust IPD surveillance in AI/AN populations.  Most cases occurred in people who had not received pneumococcal conjugate vaccine but who had a risk factor indication to be vaccinated.  This is especially true among adults 18-49 years of age.  In April the IHS Chief \nMedical Officer Dr. Christensen iss ued a call to action to administer PCV20 to all AI/AN adults \nwith an indication.  PCV21 has a great potential to prevent IPD in AI/AN adults and provides \nexcellent coverage for the serotypes causing dis ease in those ≥ 65 years of age, but does not \ncontain serotype 4, so it’s important to retain a serotype 4-containg vaccine as an option, \nespecially for AI/AN adults 18 to 49 years of age with ri sk factors for IPD. Neither PCV20 nor \nPCV21 is perfectly matched to protected against the circulating serotype s in tribal communities, \nbut where data are available, clinicians serving AI/AN patients may be able to tailor their vaccine \nrecommendations to the local epidemiology. The burden of IPD increases at a younger age \namong AI/AN adults, and historically IHS has been more successful implementing age-based rather than purely risk factor-based indications .  A recommendation for PCV21 that includes \nthose ≥50 years of age would be a benefit in the AI/AN population that IHS serves . \nMs. Phyllis Arthur, liaison representative from BIO, expressed concern with the idea that \nincreased coverage in one group would have a negative impact on equity for others. Increasing \nvaccination in all groups will result in an overarching improvement in vaccination status. \nIndustry is focused on bringing interventions to populations that will raise equity while still offering great options for all populations regardless of equity. \nDr. Rick Zimmerman, liaison representative from the Association for Prevention Teaching and \nResearch, said that he had recently been part of a team that had published a piece on the \nsocietal cost in adults of racial inequity in pneumococcal disease and the cost is $673 million for \nadults aged 50 and older. In another paper, the strategy that reduced IPD cases and deaths the \nmost in the Black population was vaccination with PCV21 at ages 50 and 65 and in the non-\nBlack population with PCV21 at ages 50 and 65. \nDr. Bob Hopkins, liaison representative from NFID, expressed strong support for recommending \nPCV21 for those ≥ 50 years with and without risk factors . \nDr. Jason Goldman, liaison representative from ACP, spoke in support of an age-based \nrecommendation beginning at age 50.  Many of his patients 60 to 65 year age range are not \nworking but not yet Medicare-eligible and don’t have medical insurance.  A recommendation at \nage 50 would be easier to implement and also could improve equity by allowing patients in that \n50 to 60 year old age range who are working and insured to be vaccinated. \nDr. Randall Morgan, liaison representative for NMA, spoke in support of an age-based \nrecommendation for pneumococcal vaccine beginning at age 50.  The life expectance for Black persons , especially Black men, is much lower than for other minorities and for whites.  The poor \nclinical outcomes for Black people also create systemic challenges associated with earlier , \nlonger , and mre serious hospitalization stays as well as possible deaths so pneumococcal \nvaccine recommendation beginning at age 50 years will certainly improve the lives of many \nBlack patients and enhance the population health of the community. \n29 \n \n   \n \n   \n  \n    \n \n \n  \n \n  \n  \n  \n \n   \n \n  \n  \n  \n  \n    \n \n  \n  \n  \n \n \n   \n  \n \n \n \n  \n  \n \n   \n  \n \n   \n   \n  \n Dr. Rick Haupt from Merck Vaccines thanked the committee for the tho rough review.  He \nreminded the committee that PCV21 was developed as an adult-specific pneumococcal vaccine \nthat due to its serotype composition addresses most of the residual pneumococcal disease in \nadults.  The expansion of a routine age-based recommendation that includes 50-to 64-year-\nolds could have substantial public health impact.  While the majority of IPD cases and \npneumonia in this age group occur among adults who have risk conditions, the current vaccine uptake in this group is far too low.  There are significant racial disparities in pneumococcal disease risk and in the prevalence of risk conditions.  Implementation of a routine age-based \nrecommendation could improve access to and uptake of pneumococcal vaccines and reduce disparities in adults 50-64 years of age with risk conditions.  Lowering the age-based \nrecommendation down to age 50 would likely improve vaccination coverage rates in all populations and could have a far greater impact on reducing disparities and improving equity ; \nthis opportunity would be lost if no expansion of the age-based recommendation occurs. The \noccurrence of clusters of serotype 4 disease does not diminish the overall positive overall \npopulation impact expected for PCV21 in adults 50 years of age and older.  ACIP can make a \nmuch simpler recommendation that will make implementation much easier through an age-\nbased recommendation. Merck has built a supply that is adequate for a broad recommendation. \nDr. Luis Jodar from Pfizer Vaccines reminded the committee that they previously had \nconsidered an age-based recommendation for PCV20 starting at age 50 but ultimately voted for an age-based recommendation for adults ≥65 years of age and risk -based recommendations for \nadults 19 to 64 years of age, so the current policy question proposes the use of PCV21 in populations that have no recommendations for use of any PCVs.  Having one PCV recommended for healthy adults ≥50 years of age and other PCV vaccines or other ages or risk \nconditions would likely complicate rather than simplify implementation of these recommendations.  All PCVs licensed for use in adults ≥ 18 years and older should be \nconsidered as options for routine vaccination of all adults ≥50 years of age.  \nDr. Kobayashi presented the work group’s proposal that ACIP recommend PCV21 as an option \nfor adults aged ≥ 19 years who currently have a recommendation to receive a dose of PCV and \nthe accompanying implementation guidance. \nDr. Long said that the rationale for the age-based recommendation for PCV21 down to age 50 \napparently was that doctors couldn’t understand and implement a risk -based recommendation , \nand she thought it would be a better investment of resources to educate doctors to do that better.  This recommendation for PCV21 down to age 50 would cost $270,000 per QALY .  She \nstated that the committee should not consider PCV20 down to age 50 so they match up because that’s $630,000 per QALY; $270,000 per QALY is unacceptable but $630,000 is outrageous.  \nDr. Talbot asked Dr. Goldman if the problem for internists in vaccinating those at high risk \nbetween 50 and 64 years of age is lack of education, or are there other reasons?  Dr. Goldman \nresponded that inter nal medicine specialists are able to read the vaccine schedule and \nunderstand the patients’ chronic conditions.  The barriers are beyond the control of physicians – \nthe Federal government, the reimbursement, the storage, the insurance companies that create \nbarriers to care, preventing physicians from being able to take care of the patients the way they need to as well as the administrative burdens that are created by the system. He stated that he \nbelieves it is imperative to have a simplified process so that physicians can delegate with \nstanding orders to their staff to make sure that patients are screened appropriately and that they \nare giving the vaccines that are needed.  It would be very simple to stock both PCV20 and PCV21 in the office and be able to implement both of them; he sees them as two separate and useful vaccines that are both needed.  \n30 \n \n  \n \n \n \n  \n \n \n  \n  \n  \n \n \n  \n \n \n  \n \n \n  \n \n \n \n \n \n \n \n  \n \n \n  \n  \n \n  \n \n  \n \n \n \n \n Lowering the age to 50 years would simplify the process because of the system dynamics that \nmake it a barrier to patient care.  He said that while he appreciates the expenditure to society, \nhe always has to go back to the only patient that matters is the one sitting in front of him, until \nhe sees the next patient, and then that’s the most important patient in the world.  He understood that the committee has to look at the cost to society, but as a practicing physician, he has to look at what is most beneficial to his patient, and he would be in favor of making sure they have access to both vaccines. \nDr. Schec hter asked if a single dose could be given at age 50 due to either durable immunity or \na change in the epidemiology of the disease due to childhood and adult vaccination, what would \nbe the cost effectiveness implications? Dr. Kobayashi responded that in the Tulane- CDC \nmodel, vaccination with PCV21 at age 50 was cost saving, but with the caveat that there was more disease due to waning, and so an additional dose was added at age 65. \nDr. Daley said that he thought it would be problematic to have a recommendation for PCV21 \ndown to age 50 but not for the other high valency vaccines such as PCV20 even though he was clear that PCV21 was a very different vaccine that was expected to provide broader protection.  He asked if the work group would bring the full proposal to ACIP in October for lowering the \nage-based recommendation to age 50 for high valency pneumococcal vaccines because he felt \nlike he did not have the information today for that big of a decision.  He acknowledged that there \nwas an opportunity cost but the data had not been presented for all high valency pneumococcal vaccines down to age 50; it’s an important question to answer, and it needs to be answered soon.  \nDr. Sandra Fryhofer, liaison representative from the American Medical Association, stated that \npneumococcal vaccination for adults is the most complicated vaccination recommendation and \nthat she thought that having a different age recommendation for PCV20 and PCV21 would add much confusion.  She stated that she supported Dr. Daley’s suggestion to come back to this issue in October. \nDr. Long stated that she thought it would be good for the work group to look at this again and to \naddress the question about the duration of protection from polysaccharide conjugate vaccines ; \nthe data that the work group saw provided no indication for protection after 12 to 15 years.  \nMaking a decision to vaccinate at 50 is most likely a decision to vaccinate again at 65, which is very expensive.  \nDr. Brooks stated that he would ask that the work group come back with a proposal for PCV20, \nbut that that would not preclude a vote today on PCV21. \nDr. Kotton said that she appreciated Dr. Goldman’s comments about the “patient in front of him” \nbut that she does feel the need for some financial stewardship and she is concerned about the \nmagnitude of the costs we are incurring, both with RSV vaccine which is quite expensive and with this vaccine, which is $319 plus administration fees.  She stated that she thought that the committee really needed to think about cost that is being added to American healthcare. \nDr. S chechter said that there’s a case for a reinforcement of pediatric vaccination. Introduction \nof new higher valency pneumococcal vaccines in adults before children misses an opportunity \nto both protect children directly and protect adults through indirect effects. Whatever the committee decides today, he hoped that there was a way to expedite access to children of \nvaccines that protect against additional serotypes. \n31 \n \n   \n \n \n \n \n \n  \n \n  \n  \n     \n \n \n \n \n \n \n \n   \n \n   \n    \n   \n  \n  \n \n   \n  \n     \n   \n \n  \n \n \n \n  \n \n \n    \n  \n    \n  \n    \n   \n         \n      \n    \n   \n Dr. Loehr made a motion that ACIP recommends PCV21 as an option for adults aged ≥19 years \nwho currently have a recommendation to receive a dose of PCV.  The motion was seconded by \nDr. Jamieson.  \nPUBLIC COMMENTS Overview \nThe floor was opened for public comment on June 27 , 2024 at 3:40 PM E DT. Members of the \npublic also were invited to submit written public comments to ACIP through the Federal \neRulemaking Portal under Docket Number ID CDC-2024-0043. Visit regulations.gov to read \nbackground documents and comments received. \nPublic Comments \nMs. Chloe Humbert \nPrivate Citizen \nMs. Humbert spoke in favor of better vaccine promotion campaigns from the government. The \nrecommendation for a Spring COVID v accine boost for seniors was not well-promoted. She \nexpressed concern that the recommended additional dose in the spring excluded 50- to 64-\nyear-olds with underlying conditions—p eople clearly at risk of hospitalization or death. \nShe stated that this lack of a vaccine campaign is persistent failure and antivaccine sentiment \nhas been coming from inside of government. She spoke very critically about the antiva ccine \ncampaign implemented outside the United States by the Department of Defense.  She stated \nthat this disinformation campaign was reported to have undermined vaccination and also \nmasking and testing. Even though the campaign was forbidden by law from targeting \nAmericans , in an interconnected w orld during a global pandemic , the idea of undermining p ublic \nhealth abroad without harming Americans is ridiculous on its face and harming innocent civilians \nabroad during a global health crisis is not itself defensible. CDC officials may think that this is \nnot the fault or responsibility of the CDC , but that's false. R eal people are counting on the CDC . \nLeadership cannot rest on laurels or point finger s elsewhere . Infectious disease doesn't \nrecognize geopolitical boundaries or federal agency silos . CDC should have a distinct and \npurposeful goal of actually promoting public health and leading vaccination promotions with an active campaign. \nMeghan Rapp\nPrivate Citizen \nMs. Rapp expressed her appreciation to ACIP members for their important work in making \nvaccine recommendations. She shared her concerns as a mother of 2 young children about the \ntiming, access, and frequency of COVID boosters for young children. In the South, schools start \nin August. All populations , including children, need access to the updated COVID -19 vaccines \nas soon as possible so that there’s time to get children into the pediatrician's office or health \ndepartment before August; October is not acceptable timing. She asked for an increase in \nvaccine options available for young children, including Novavax for under 12 years of age. She \nstated that she knows many parents who would prefer that option and that its availability would \nhelp with vaccine uptake among young children . She also described challenges of access to \nvaccination sites faced by parents because pharmacies may not be able to or be willing to \nvaccinate younger children.  \n32 \n \n    \n     \n \n  \n     \n \n \n \n \n \n \n    \n   \n   \n   \n  \n  \n    \n    \n  \n    \n   \n  \n \n   \n \n \n  \n   \n \n  \n \n \n \n \n \n \n  \n  \n   \n  \n  \n    \n     \n \n  \n    \n    \n \n  It takes more time to visit a pediatrician’ s office and not all pediatricians offices will carry COVID \nshots .  It would increase the vaccine uptake rate if COVID boosters for children were available \nin July when these back -to-school appointments are beginning. She also requested that the \nrecommended frequency of boosters be increased for all ages. With waning immunity following \nvaccination, changes in variants, the inability of small children to mask , and states banning \nmasks, fewer prevention strategies are available . \nDr. Brian Koffman \nCo-Founder and Executive Vice President \nChronic Lymphatic Leukemia (CLL) Society \nDr. Koffman introduced himself as a retired family doctor and a chronic lymphatic leukemia \n(CLL) patient. He explained that all CLL patients are immunocompromised regardless of their \ntreatment status and like other immunocompromised communities , CLL patients were \ndisproportionately affected by COVID -19. He stated that it is also wel l-documented that the \nresponse of immunocompromised persons to vaccines is less predictable and robust than that \nof the general population and expressed appreciation to ACIP for recognizing the \nimmunocompromised as a special category requiring specific recommendations .  He pointed \nout that often the evidence to make these recommendations is weaker than that for other \nvaccine recipients for whom data from randomized clinical trials are available; \nimmunocompromised persons are often excluded from these trials , so decisions end up being \nmade by expert consensus.  He requested that ACIP , when appropriate, push to include the \nimmun ocompromised in clinical trials so higher quality data are available to inform \nrecommendations. \nHe asked ACIP to coordinate its efforts to integrate every available immune measure, including \nvaccines and pre-exposure prophylaxis , with disease-specific monoclonal antibodies to offer the \nimmunocompromised their best package of protection, including both active immunity through \nvaccination and passive through antibodies.  He also requested that ACIP revisit the near \nuniversal prohibition against live vaccines in the immuno compromise d and to find ways to \nexplore the safety and efficacy of live vaccines rather than dismiss them all as too risky and \nleave immunocompromised persons completely unprotected. \nStanley Plotkin, MD\nUniversity of Pennsylvania \nDr. Plotkin stated his support for the development of more combination vaccines.  Combination \nvaccines decrease the amount of time post-vaccination when an unrelated illness could be \nascribed to a vaccine, decrease required medical visits, and could increase collaborations among manufacturers.  He stated that he hoped the ACIP w ould express enthusiasm for \ncombined vaccines to induce manufacturers to work together and also to advance vaccine \ncoverage. He also said that he was happy to see that chikungunya vaccine was under \nconsideration. Chikungunya can be devastating to those infected, even if mortality is low . He \nreminded the committee that chikungunya is now a worldwide disease and as global warming \nincreases , it will inevitably spread N orthward. Dr. Plotkin stated that he has been a consultant to \nValneva about their chik ungunya vacci ne and said he was happy to see it progress to licensure. \nHe stated that the best way to prevent outbreaks is to produce an immune human population. \nWaiting for an outbreak and responding only then is a recipe for increased individuals with \nchronic problems due to c hikungunya. He expressed his hope that ACIP w ould eventually \nrecommend prophylactic vaccination in areas where there are Aedes mosquitoes. \n33 \n \n   \n \n \n \n  \n     \n   \n  \n  \n   \n  \n \n     \n   \n \n \n \n \n \n    \n    \n  \n   \n \n    \n   \n \n \n   \n   \n   \n \n \n \n  Jamie Schanbaum J.A.M.I.E. Group \nMs. Schanbaum shared her experience as a survivor of meningitis.  She was a college student \nand like many meningitis patients , came out of the hospital as an amputee.  She stated that she \nwas hospitalized for 7 months and at discharge weighed 80 pounds and had lost all of her hair.  \nShe expressed regret that she went to college without having been vaccinated and almost lost her life to it. She said that she knew people whose children had not survived meningitis, and she \nwanted to be the voice for them.  She reminded the committee that meningitis is commonly misdiagnosed due to the initial nonspecific symptoms and said that she had known someone in whom the diagnosis was initially missed, and when they returned to the hospital, they were \ndeclared brain dead within 18 hours from their first symptom of meningitis . Ms. Schanbaum said \nthat was why she was speaking, because she didn’t want anyone to go through what she had \ngone through. She said that she recently had her leg re-amputated 2 years ago because of an \nill-fitted prosthetic. She thanked the committee for listening . \nDon Ford \nOrganizing for a Better Tomorrow \nMr. Ford said that the role of the CDC is to set guidance that will protect people from disease, \nbut a large amount of anti-vaccine propaganda, state representatives trying to ban conventional \nmasking, and mutating variants, it's a challenging time for people to protect themselves . The \ndiseases discussed today are a risk to everyone, not simply the immunocompromis ed. Looking \nonly at mortality underestimates impact when any single infection can destroy someone's quality \nof life forever . He stated that people need to do everything they can to limit the risks . \nHe advocated for an earlier vaccine roll out, recommendations for both mRNA and protein \nsubunit COVID -19 vaccines, and for two dose recommendations due to development of new \nvariants and imprinting in response to previous vaccination . CDC and FDA should consider \nmeeting twice a year to discuss variants and recommend updates to vaccines if needed. As the Bridge Program is expiring, access to insurance is the only way that people can access these \nlifesaving vaccines. New recommendations determine not only if people can access them , but \nwhether insurance will cover the once free but now cost-prohibitive vaccines . He spoke in \nsupport of authorization of Novavax for children. He expressed concern about state legislatures \nbanning masks or other personal airborne protections under the guise of security . He also said \nthat H5N1 should be taken more seriously, that it is a ticking time bomb that needs to be \ndiffused before it goes off. \n34 \n \n  \n \n \n \n     \n \n     \n   \n    \n   \n  \n     \n  \n   \n     \n     \n     \n  \n  \n     \n \n   \n  Ashlie White \nAmputee Coalition \nMs. White spoke on behalf of The Amputee Coalition, which supports and advocates on behalf \nof the 5.6 million Americans with limb loss and limb difference and their families , caregivers , and \nclinicians. She appreciated the opportunity to comment about the important role vaccines play in \nprotecting their community . Well over half of the more than 5.6 million individuals missing limbs \nin the US have serious underlying health conditions , including diabetes, peripheral arterial \ndisease, and cancer —illnesses that have been shown to be the most likely causes of limb loss \nand of themselves are significant risk factors in increasing anyone's vulnerability. Limb loss \npatients have additional burdens . There is impact on patient health from living with reduced \nmobility , as well as the challenge of obtaining medical services , as travel can often present both \nphysical and economic barriers to seeking care. “L imb difference” is the phrase used to describe \ndifferences in the size, shape, or structure of a limb when compared to what is considered \nmedically normal . Limb loss and limb difference patients need to be a ble to know about, \nunderstand, and easily access the vaccines which CDC recommends for them. E nsuring our \ncommunities understand the vaccines that are available to them and have easy access to get \nthem can really make a difference; however, confusion over CDC recommendations , insurance \ncoverage, or having to make multiple trips to a provider to get vaccinated for one condition at a \ntime can present real and formable burdens to our community members . She urged the \ncommittee to consider this community when developing vaccine recommendations and to make \nsure that recommendations are as clear and b road as possible to support and increase \nawareness and access by those who would most benefit. \n35 \n \n  \n \n \n   \n \n \n  \n  \n \n \n   \n \n   \n    \n   \n    \n   \n \n      \n  \n        \n         \n \n \n \n \n  \n  \n \n \n \n \n \n \n \n    \n \n   \n \n     \n     \n \n       \n  \n        \n      \n  \n \n VOTES \nVote: COVID -19 Vaccines \nDr. Keipp Talbot, ACIP Chair , read the following proposed ACIP voting language into the record \nfor COVID -19 vaccines: \nACIP recommends 2024– 2025 COVID-19 vaccines as authorized or approved by FDA \nin persons ≥6 months of age. \nMotion/Vote: COVID -19 Vaccines \nDr. Daley made a motion to approve the proposed recommendation as written stating, “ACIP \nrecommends 2024– 2025 COVID -19 vaccines as authorized or approved by FDA in persons ≥6 \nmonths of age” Dr. Brooks seconded the motion. Dr. Maldo nado declared a COI due to serving \nas the Stanford PI for the Pfizer pediatric COVID -19 and RSV vaccine trials and adult varicella \nvaccine trials . No other COIs were declared. The motion carried with 11 favoring, 0 opposing, \nand 1 abstaining. The disposition of the vote was as follows: \n11 Favored: Brooks, Chen, Cineas, Daley, Jamieson, Kotton, Loehr, Long, Schec hter, \nShaw, Talbot \n0 Opposed: N/A \n1 Abstained: Mald onado \nVote: Pneumococcal Vaccines \nDr. Talbot, ACIP Chair , read the following proposed ACIP voting language into the record for \npneumococcal vaccines: \nACIP recommends PCV21 as an option for adults aged ≥19 years who currently have a \nrecommendation to receive a dose of PCV. \nMotion/Vote: Pneumococcal Vaccines \nDr. Loehr made a motion to approve the proposed recommendation as written stating, “ ACIP \nrecommends PCV21 as an option for adults aged ≥19 years who currently have a \nrecommendation to receive a dose of PCV.” Dr. Jamieson seconded the motion. Dr. Maldondo \ndeclared a conflict due to serving as the Stanford PI for the Pfizer RSV and COVID -19 vaccine \ntrials and adult varicella vaccine trials. No other COIs were declared. The motion carried with 11 \nfavoring, 0 opposing, and 1 abstaining. The disposition of the vote was as follows: \n11 Favored: Brooks, Chen, Cineas, Daley, Jamieson, Kotton, Loehr, Long, Schechter, \nShaw, Talbot \n0 Opposed: N/A \n1 Abstained: Maldonado \n36 \n \n  \n    \n \n \n \n  \n \n \n  \n \n    \n \n   \n       \n    \n \n \n      \n  \n        \n        \n \n \n  \n \n  \n  \n \n \n  \n \n \n \n  \n \n   \n     \n      \n    \n         \n          \n       \n    \n \n                   \n        \n         \n \n Vote #1: Influenza Vaccines \nDr. Talbot, ACIP Chair , read the following proposed ACIP voting language into the record for the \nfirst influenza vaccines vote: \nACIP reaffirms the recommendation for routine annual influenza vaccination of all \npersons aged ≥6 months who do not have contraindications. \nMotion/Vote #1: Influenza Vaccines \nDr. Kotton made a motion to approve the proposed recommendation as written for influenza \nvaccination stating, “ACIP reaffirms the recommendation for routine annual influenza vaccination of all persons aged ≥6 months who do not have contraindications .” Dr. Daley \nseconded the motion. Dr. Maldonado declared a COI as the Stanford PI for Pfizer pediatric RSV \nand COVID -19 vaccine trials and adult varicella vaccine trials . No other COIs were declared. \nThe motion carried with 11 favoring, 0 opposing, and 1 abstaining. The disposition of the vote \nwas as follows: \n11 Favored: Brooks, Chen, Cineas, Daley, Jamieson, Kotton, Loehr, Long, Schechter, \nShaw, Talbot \n0 Opposed: N/A \n1 Abstained: Maldonado \nVote #2: Influenza Vaccines \nDr. Talbot, ACIP Chair , read the following proposed ACIP voting language into the record for the \nsecond influenza vaccines vote: \nACIP recommends high-dose inactivated (HD -IIV3) and adjuvanted inactivated (aIIV3) \ninfluenza vaccines as acceptable options for influenza vaccination of solid organ transplant recipients aged 18 through 64 years who are receiving immunosuppressive medication regimens, without a preference over other age-appropriate IIV3s or RIV3. \nMotion/Vote #2: Influenza Vaccines \nDr. Kotton made a motion to approve the proposed recommendation as written stating, “ACIP \nrecommends high- dose inactivated (HD -IIV3) and adjuvanted inactivated (aIIV3) influenza vaccines as \nacceptable options for influenza vaccination of solid organ transplant recipients aged 18 through 64 years \nwho are receiving immunosuppressive medication regimens, without a preference over other age-appropriate IIV3s or RIV3. ” Dr. Loehr seconded the motion. Dr. Maldonado declared a COI as the \nStandford PI for Pfizer pediatric COVID -19 and RSV vaccine trials and adult varicella vaccine trials. No \nother COIs were declared. The motion carried with 11 favoring, 0 opposing, and 1 abstaining. The disposition of the vote was as follows: \n11 Favored: Brooks, Chen, Cineas, Daley, Jamieson, Kotton, Loehr, Long, Schechter, Shaw, Talbot \n0 Opposed: N/A \n1 Abstained: Maldonado \n37 \n \n    \n \n \n    \n  \n  \n \n \n   \n   \n \n    \n \n     \n      \n  \n \n     \n \n \n      \n \n   \n   \n   \n       \n \n \n \n \n \n      \n \n   \n     \n \n \n   \n \n  Dr. Talbot invited ACIP members to make comments following the votes. \nDr. Loehr commented that there have been recommendations for 18 to 64 years of age and for \n≥19 to 64 years of age. He wondered if this could be consistent in the future if there is a \nrationale for one versus the other. It is confusing because the VFC considers through age 18, \nwhich may be the reason why sometimes there is confusion. \nDr. Wharton indicated that this also may have to do with the data that are available for certain \ndiseases in terms of when historically the recommendations were originally put together , but it is \nan inconsistency that does create another type of challenge. \nDr. Talbot reminded everyone that it was mentioned earlier in the day that insurance has a year \nto pay for vaccines . It is interesting that the ACIP has a mandate to review and vote on a \nvaccine very quickly after FDA licensure, but insurance has a year. It seems just as imperative \nfor insurance companies to have an abbreviated time following an ACIP vote to start paying for \nthese vaccines. This should be considered in the near future. \nDr Kotton seconded the concern about insurance companies. Given that it is CMS policy that \ngives insurers a year, CMS would need to alter its policy , which would then influence private \ninsurance. \nMs. Hance from CMS clarified that this would require a modification of the Affordable Care Act \n(ACA) that gave private insurance a year after a vaccine is recommended . \nDr. Kotton said that similarly, she would like to ask that CMS and other regulatory bodies \nconsider how vaccines are being supplied and the fact that many of practitioners cannot give \nvaccines that are covered under Medicare Part D in their offices . The minute the patient leaves \na clinic with a recommendation to go to a commercial pharmacy , they often do not get the \nvaccines they need. This is a major impediment toward broad vaccination of adults. As they had \nseen during the first 2 days of this meeting, there are missed opportunities to prevent vaccine-\npreventable illness es. Support on the regulatory aspects of vaccine coverage would be much \nappreciated. \nDr. Brooks pointed out that regarding the discussion about PCV being moved down to be \nuniversally recommended at age 50 in the interim while the ACIP further deliberates on this, \nthey could focus on those who already have the indication for the vaccines that are now \navailable who are not getting vaccinated—the 30% to 50% who are of high risk who are \nunvaccinated in that age group. \nWith no additional business posed for the day , the ACIP meeting stood in recess until 8:00 AM \non June 28, 2024. \n38 \n \n   \n \n \n \n \n \n  \n  \n \n   \n    \n   \n   \n \n \n \n \n    \n  \n \n  \n \n \n     \n \n  \n \n \n  \n    \n  \n \n \n  \n \n  \n    \n      \n   \n   \n    FRIDAY: JUNE 2 8, 2024 \nWELCOME AND INTRODUCTIONS \nCall to Order/Roll Call \nDr. Keipp Talbot, ACIP Chair , called to order and presided over the third day of the June 26-28, \n2024 Centers for CDC ACIP meeting. She conducted a roll call, which established that a \nquorum was present. A list of Members, Ex Officios , and Liaison Representatives is included in \nthe appendixes at the end of this summary document. One COI was declared by Dr. \nMaldenado, who is the Stanford PI for the pediatric COVID vaccine and RSV vaccine trials , and \nadult varicella trials. Dr. Talbot noted that this was the last meeting for several ACIP members, \nincluding Dr. Chen, Dr. Daley, Dr. Kotton, and Dr. Long. Each of them shared a few thoughts \nabout their tenure on the ACIP. \nPRESENTATIONS \nThe m eningococcal vaccines session began with an introduction by Dr. Jamie Loehr, Chair of \nthe ACIP Meningococcal /Hib Vaccines Work Group. The work group is reviewing GSK’s \ncombination MenABCWY vaccine, which could be licensed soon, as well as continuing to \nconsider changes to the adolescent meningococcal vaccine schedule.  The policy questions \nunder consideration by the work group for GSK’s MenABCWY vaccine are:  should the pentavalent vaccine be included as an option for MenACWY/MenB vaccination in people \ncurrently recommended to receive both vaccines at the same visit; should the pentavalent \nvaccine be included as an option for people currently recommended to receive MenACWY onl y; \nand s hould the pentavalent vaccine be included as an option for people currently recommended \nto receive MenB only . Dr. Loehr shared that the work group anticipates presenting GRADE and \nthe Evidence-to-Recommendations (EtR) framework along with an economic analysis for the \nGSK MenABCWY vaccine at the October ACIP meeting in preparation for a possible vote in February 2025, if the vaccine is licensed by that time. \nMs. Amy Rubis, Division of Bacterial Diseases, CDC, presented an update on the epidemiology \nof meningococcal disease in the United States.  Meningococcal disease cases are reported to CDC through the National Notifiable Diseases Surveillance System (NNDSS ). Additional \nserogroup and outcome information along with other clinical characteristics are collected from \nall jurisdictions through Enhanced Meningococcal Disease Surveillance (EMDS ). All available \nisolates are also submitted to CDC for whole genome sequencing. Meningococcal disease \nsurveillance data are typically finalized in the fall of the following year; 2023 data are still \npreliminary.  Meningococcal disease incidence in the US declined dramatically between 1996 \nand 2019, with further declines in 2020 and 2021. In 2022 to 2023, reported cases have \nrebounded. Based on preliminary 2023 data, 423 cases have been reported, which equates to \nthe highest incidence since 2014. The 2023 increase was predominantly due to a dramatic \nincrease in Neisseria meningi tidis serogroup Y (NmY). In many jurisdictions, the increases are \nprimarily due to NmY sequence type (ST) 1466 (clonal complex CC174), which is susceptible to all treatment and prophylaxis antibiotics.  Of cases for which data are available, 64% are among \nBlack or African Am erican persons. Sixty-two percent of cases presented with bacteremia.  Only \n4 cases were in individuals who received MenACWY vaccine, and none were up to date with MenACWY according to ACIP recommendations. \n39 \n \n   \n \n  \n \n \n  \n \n \n   \n \n    \n   \n  \n   \n  \n \n \n  \n  \n \n \n  \n   \n \n   \n  \n \n \n  \n   \n  \n \n   \n \n \n \n   \n \n   \n \n \n \n \n   Cases associated with NmY ST-1466 were almost all among adults and have been detected \nacross the U.S. but seem to be concentrated on the East Coast. For 2024, as of June 11, 251 \ncases have been reported to CDC, compared to 164 cases as of this date in 2023. Of those with known serogroup, 103 (57%) are NmY. \nLooking at overall meningococcal disease epidemiology during the period 2012 to 2021, \nincidence and serogroup distribution vary by age group with the highest incidence observed in \nchildren aged less than 2 years and adults aged greater than 85 years.  A peak in incidence is \nalso observed among adolescents and young adults aged 16-20 years. Serogroup B is the \npredominant serogroup in children aged less than five years ; in children and adolescents aged \n5-20 years, serogroup B accounts for approximately half of cases and in adults aged greater \nthan 20 years, serogroups C, W, and Y cause the majority of disease. Incidence was lower across age groups in 2022 and 2023, but there was a peak in disease in 26-64 year olds, driven \nby the ST-1466 NmY cases.  In 2022 and 2023 an increase in incidence among Black or African \nAmerican persons consistent with the demographic characteristics of the ST-1466 cases driving the increase in incidence in these years . From 2015 to 2023, incidence rates among 11-20 year \nolds were highest for Black or African American persons and by ethnicity, for non-Hispanic \npersons. \nBoth penicillin resistant and ciprofloxacin and penicillin resistant cases that are mostly \nserogroup Y are being identified. This strain is not related to the ST-1466 cases; these are \nmainly sequence type 3587 with some isolates in closely related STs. This strain is \ndisproportionately affecting Hispanic individuals .  Ciprofloxacin-resistant only cases are also \nbeing seen; these are mostly sporadic cases and not related to the ST-3587 strain. In 2023 and \n2024 there have been increases cases due to penicill in resistant as well as ciprofloxacin and \npenicillin resistant N. meningitidis . An increase in ciprofloxacin resistant only cases is also \nbeing seen. Most of the dual resistant and penicillin resistant cases are NmY or have an NmY \nbackbone and they appear to be genetically related. CDC has recently provided guidance to avoid the use of ciprofloxacin for prophylaxis of close contacts of patients with meningococcal \ndisease in areas with ciprofloxacin resistant cases. \nSince 2022, 9 outbreaks have occurred, including a large serogroup C outbreak among men \nwho have sex with men; a small serogroup C outbreak among people experiencing homelessness ; a small serogroup B outbreak in a college and surrounding community ; a large \nstatewide serogroup Y ST1466 outbreak ; a serogroup W community outbreak ; an outbreak of \nserogroup B in an Amish community ; another outbreak among people experiencing \nhomelessness, this one serogroup Y ; one outbreak in a correctional facility ; and an outbr eak \nassociated with travel to the Kingdom of Saudi Arabia. \nIn summary, incidence of meningococcal disease increased in 2023 to above prepandemic \nlevels, and this increase was primarily driven by serogroup Y ST-1466 cases. The increasing \nburden of disease driven by ST-1466 NmY is being observed primarily among those aged 30-60 years. We don't know if that is just the epidemiology of this strain or if the adolescent vaccination program is successfully protecting the preteens, teens, and young adults. Ciprofloxacin resistance is increasing both domestically and in imported cases, and multiple jurisdictions have moved away from using ciprofloxacin for prophylaxis of close contacts of \npatients with meningococcal disease. A growing number of the isolates resistant to ciprofloxacin \nare serogroups other than Y. ST1466 is predominately affecting Black or African American persons, leading to an increasing disparity in incidence among Black persons compared to other \nracial groups. \n40 \n \n  \n    \n  \n \n \n  \n  \n \n    \n \n    \n \n    \n \n \n \n \n   \n   \n    \n   \n \n \n   \n    \n  \n   \n   \n  There have been a large number of outbreaks since 2022, and in many cases these outbreaks \nare affecting minorities (e.g., B lack or Muslim communities ) or disadvantaged populations \n(people experiencing homelessness or people who are in prison) . \nDr. Wendy Sohn, GSK, presented immunogenicity and safety data on GSK’s MenABCWY \nvaccine. GSK’s vaccine is built on the components of MenACWY (Menveo) and MenB -4C \n(BEXSERO ), with licensure of the combined product anticipated in 2025.  The proposed \nindication for MenABCWY is for active immunization to prevent invasive disease caused by \nNeisseria meningitidis serogroups A, B, C, W, and Y in individuals 10 through 25 years of age, \nwith 2 0.5 mL doses administered intramuscularly at least 6 months apart.  Dr. Sohn presented an overview of GSK’s clinical program, with a summary of study results that demonstrated the safety and immunogenicity of MenABCWY in adolescents and young adults.  MenABCWY was non-inferior to MenACWY -naïve and -primed participants. Investigators were also able to \ndemonstrate an immune response against a diverse group of serogroup strains that was non-inferior to MenB-4C.  Persistence of antibody response to MenB strains was demonstrated at 24 months.  Solicited local and systemic adverse events within 7 days were monitored after \nMenAB CWY, MenB -4C or MenACWY; reported adverse events were generally mild-to-\nmoderate, with mean duration of 1-4 days, depending on the adverse event.  Adverse events \noccurred at similar rates after MenABCWY and MenB -4C, and higher than after MenACWY.  No \ndifferences in adverse events were observed between the 1\nst and 2nd dose of MenABCWY. \nDr. Sarah Schillie, Division of Bacterial Diseases, CDC, then presented work group \nconsiderations regarding MenABCWY vaccine and on potential risk groups for MenB vaccination.  In their review of GSK’s clinical development program, they noted that the \ndemographics of the clinical trial participants may not be reflective of that of the U.S. population but rather reflective of the countries in which the trials occurred.  The work group found that the safety profile of pentavalent vaccine was favorable and similar to that of MenB (and more adverse events occurred for pentavalent compared to MenACWY).  Regarding immunogenicity, pentavalent was non-inferior to MenACWY in most study groups.  The comparison of 1 dose \npentavalent vs. 1 dose MenACWY in naïve recipients was not powered for noninferiority, \nalthough results were favorable for all serogroups except A.  MenABCWY was non-inferior to \nMenB based on GSK’s endogenous complement human bactericidal antibody assay .  \nMenABCWY was non-inferior to MenB 0,2 months for 3 components (fHbp, NadA, NHBA) and \nMenB  0,6 months for 2 components (fHbp, NadA) based on hSBA.  After 24 months, titers \nwaned substantially for serogroup A and for B components fHbp, NHBA, and PorA.  A robust \nbooster response was elicited. The work group was concerned about the drop in protection at 2 years for serogroup B . \nOptions for revising the adolescent meningococcal vaccine schedule were presented to ACIP in February.  With the current schedule, MenACWY is recommended at 11-12 years and at 16 \nyears, and MenB vaccine is recommended at 16-23 years based on SCDM.  Options under \nconsideration include, in addition to the current schedule, keeping MenACWY as in the current \nschedule and either recommending MenB for all adolescents at age 16 years and again at age 17-18 years, or for adolescents at higher risk for MenB at those same ages. The dose of MenACWY recommended at 11-12 years could be dropped and a single dose given at age 16 years , with Men B at 16 years and 17-18 years either for all adolescents or for those at higher \nrisk. Finally, MenACWY could be given at 15 years and 17-18 years and Men B (2 doses) at \n17-18 years. Because changing the MenB recommendations to risk -based is under \nconsideration, the work group has considered groups of adolescents at higher risk for MenB, based on congregate living settings. \n41 \n \n   \n \n \n   \n \n \n \n  \n    \n \n \n \n  \n  \n  \n  \n   \n  \n \n  \n   \n  \n \n   \n \n  \n    \n \n   \n \n \n \n \n    \n \n  \n This would include adolescents planning to attend college and adolescents in a congregate \nliving setting (e.g., congregate foster care, boarding school, correctional facility, etc.) who are \nanticipated to remain in this setting long enough to complete the MenB vaccine series .  \nAdditionally, any adolescent who desires protection may receive MenB vaccine, even if they are \nunsure of their future plans which may inform congregate living risk . \nDr. Sarah Long opened the session on maternal and pediatric RSV with a report from the ACIP Maternal/Pediatric RSV Work Group.  Dr. Long reminded the committee of the current \nrecommendations for either vaccination in pregnancy or administration of nirsevimab for \nprotection of infants from severe RSV disease.  Vaccine administration errors have been \nreported to the Vaccine Adverse Event Reporting System, including reports of pregnant persons receiving GSK’s vaccine for older adults; reports of children receiving RSV vaccine instead of \nnirsevimab or of young children receiving the wrong dose of nirsevimab. CDC has made \nadditional educational materials available to healthcare providers to support appropriate use of \nthese products.  \nDr. Shannon Stokley, Immunization Services Division, CDC, provided an update on \nimplementation and uptake of nirsevimab and the maternal RSV vaccine. In the Vaccine Safety \nDatalink, 17.8% of pregnant persons had received the maternal RSV vaccine by January 31, \n2024. Vaccination coverage varied by race and ethnicity, ranging from 10.3% among Black pregnant persons to 24.8% among Asian pregnant persons. According to the March 2024 National Immunization Survey, 41% of infants <8 months of age received nirsevimab during the \n2023-2024 season.  Fifty -one percent of infants are estimated to have been protected from RSV \nby either receipt of nirsevimab or maternal RSV vaccination. For the 2024-2025 season, \nmaternal immunization should resume in most of the continental U.S. on September 1, and \nnirsevimab administration should resume in the same areas on October 1; nirsevimab is \nexpected to be broadly available by that time.  During the 2023-202 4 season there were a \nnumber of challenges with maternal RSV vaccination including cost and reimbursement issues, \naccess issues (e.g., lack of supply at many OBGYN offices , requirement for a prescription at \npharmacies), lack of data on coadministration, and lack of linkage of maternal and infant \nimmunization records; for nirsevimab, the timing of licensure and ACIP recommendations provided little time for planning of distribution and rollout, and there were uncertainties about insurance coverage and demand rapidly outpaced supply. Due to the limited supply, CDC issued a Health Advisory via the Health Alert Network recommending that available doses be \nprioritized to younger and high-risk infants.  By January, demand had decreased and additional \nsupply was available, allowing return to the original recommendations. Jurisdictional \nimmunization programs have targeted birthing facilities for enrollment in the VFC program to \nfacilitate administration of nirsevimab to VFC -eligible newborns; birthing hospitals can enroll in \nVFC as “specialty providers,” only offering nirsevi mab and the hepatitis B vaccine birth dose. \nDr. Pedro Moro, Immunization Safety Office, DHQP , presented to the committee on maternal \nRSV vaccine safety surveillance.  In clinical trials among pregnant persons at 24– 36 weeks’ \ngestation, more preterm births were noted among Pfizer RSV vaccine recipients compared to placebo, although the differences were not statistically significant. Post- licensure safety \nsurveillance of the Pfizer RSV vaccine in pregnant persons was initiated during the 2023-2024 season.  The patterns of reported local and systemic (e.g., headache) symptoms in V -safe and \nVAERS after maternal Pfizer RSV vaccine were consistent with its pre-licensure safety profile.  Among reports received in VAERS after maternal Pfizer RSV vaccine, the most frequent adverse events reported were pregnancy -specific conditions (e.g., preterm delivery), as \nexpected for a vaccine recommended at 32-36 weeks’ gestational age.  \n42 \n \n  \n \n \n     \n \n \n \n \n \n   \n   \n \n  \n  \n \n \n  \n \n  \n \n \n \n  \n \n \n \n \n \n \n  \n \n  Preliminary findings in the VSD observed that the incidence of preterm births is 4.1% among \npregnant persons who received Pfizer RSV vaccine during the 2023-2024 respiratory season. \nThis was within the expected range of the incidence of preterm births at 32-36 weeks’ \ngestation (3.1 -6.1%) before introduction of this vaccine.  CDC and FDA will continue to monitor \nmaternal RSV vaccine safety in VAERS, V -safe and VSD. \nDr. Amanda Payne, Coronavirus and Other Respiratory Viruses Division, CDC, provided an \nupdate on post-licensure effectiveness of nirsevimab.  A test-negative design analysis of first \nseason nirsevimab product effectiveness against RSV -associated emergency department ( ED) \nencounters and hospitalization was conducted in VISION , a multi-site network of electronic \nhealth records, including 127 emergency rooms and 107 hospitals. In this analysis infants aged less than 8 months as of October 1, 2023, or those born after October 1, 2023 who visited a participating ED for or were hospitalized with RSV -like illness (RLI) and were tested for RSV \nwere included.  Cases were those with RLI and a positive RSV antigen or nucleic acid \namplification test (NAAT), and controls were those with RLI and a negative RSV NAAT test.  Encounters during October 8, 2023, through March 31, 2024, were included.  Encounters were excluded if they were aged less than 7 days at the time of their encounter, maternal RSV vaccination history could not be verified, there was evidence of maternal RSV vaccination or \npalivizumab administration, unrecommended nirsevimab doses were received, there was less \nthan 7 days between the nirsevimab dose and the RLI encounter, or the RSV test result was indeter minate.  The adjusted odds ratio comparing the odds of immunization among the case \nversus the controls was estimated using multivariable logistic regression, and product effectiveness (or PE) was calculated as 1 minus the adjusted odds ratio times 100%.  Nirsevimab was effective against RSV-associated ED encounters and hospitalization among \ninfants in their first RSV season.  Among about 5,000 ED encounters for RSV -like illness among \ninfants in their first RSV season, 442 had evidence of nirsevimab receipt 7 days more prior to the encounter, with a median time since dose of 53 days.  RSV percent positivity was lower among those that had evidence of nirsevimab receipt compared with those without evidence of nirsevimab receipt, and the adjusted estimate of product effectiveness was 77%, with a \nconfidence interval from 69% to 83%.  Among 1,000 hospitalizations for RSV -like illness among \ninfants in their first RSV season, 93 had evidence of nirsevimab receipt 7 days or more prior to \nthe hospitalization, with a median time since dose of 48 days.  The adjusted estimate of product effectiveness against RSV-associated hospitalization was 98%, with a confidence interval from 95% to 99%. \nAnother study using test-negative design was done in the New Vaccine Surveillance Network, a \nprospective, population- based surveillance network for pediatric acute respiratory illness (ARI) \nat 7 U.S. medical centers.  N irsevimab was effective against medical -attended RSV- associated \nARI episodes and RSV-associated hospitalization.  Among nearly 1,700 ARI episodes among \ninfants in their first RSV season, 120 had evidence of nirsevimab receipt 7 days more prior to \nsymptom onset, with a median time since dose of 42 days.  RSV percent positivity was lower \namong those that had evidence of nirsevimab receipt compared with those without evidence of nirsevimab receipt, and the adjusted estimate of product effectiveness was 89%, with a confidence interval from 77% to 94%.  Among 870 hospitalizations for ARI among infants in their first RSV season, 63 had evidence of nirsevimab receipt 7 days or more prior to ARI symptom onset, with a median time since dose of 38 days.  The adjusted estimate of product \neffectiveness was 91%, with a confidence interval from 79% to 96%.  \n43 \n \n   \n  \n \n \n \n \n \n  \n   \n    \n    \n  \n      \n  \n \n \n  \n  \n \n \n \n \n  \n \n   \n  \n  \n \n \n \n  \n  \n \n  Together these data indicate nirsevimab was effective against RSV -associated ED encounters \nand hospitalization among infants in their first RSV season during the 2023-2024 RSV season.  \nHowever, due to the timing of authorizations and recommendations of RSV prevention products \nand RSV activity during the 2023-2024 RSV season, these results should be interpreted with caution.  US -based analyses may be subject to residual confounding due to prioritization of \nnirsevimab doses, and the short time between nirsevimab administration and outcomes limited the ability to assess duration of protection.  Further, there was limited ability to assess effectiveness of maternal RSV vaccines during the 20230-2024 RSV season.  CDC will continue \nmonitoring post-licensure product effectiveness. \nDr. Jefferson Jones, Coronavirus and Other Respiratory Viruses Division, CDC, shared \nconsiderations from the ACIP Maternal /Pediatric RSV Work Group.  For the 2024-2025 season, \nno supply/demand mismatch is anticipated for the maternal RSV vaccine.  There will be limited \navailability of nirsevimab beginning early September, and the product is expected to be broadly \navailable by October 1.  The o riginal ACIP recommendations for nirsevimab apply for 2024-25 \nRSV season; all infants are recommended to be protected by either maternal RSV vaccination or nirsevimab. Dr. Jones summarized the post-licensure safety data for the maternal RSV \nvaccine.  There have been no verified reports of Guillain-Barré syndrome following RSV \nvaccination in pregnancy and a preliminary analysis of preterm births in the Vaccine Safety Datalink suggest that the incidence of preterm births following Pfizer’s RSV vaccine is within the expected range.  Nirsevimab safety is monitored through FDA’s drug safety surveillance system .  The most frequently reported adverse events involved patients who reportedly \ndeveloped breakthrough RSV infections despite receiving nirsevimab, and included signs, symptoms, or complications of these infections (e.g., bronchiolitis).  Cases of serious \nhypersensitivity reactions with nirsevimab were identified in the post-marketing setting and the \nproduct labeling was updated in February 2024.  The work group found the safety data on \nnirsevimab and maternal RSV vaccine reassuring, but population-based studies with comparison groups are needed and pending.  Because of U.S. recommendation that Pfizer maternal RSV vaccine be given at 32– 36 weeks gestation, U.S. data on safety of vaccine given \nearlier in pregnancy is unlikely to become available.  The work group also noted, in their discussion of the nirsevimab safety findings, that hypersensitivity reactions in young infants are rare and can be difficult to discern from startle reactions or vasovagal reactions . \nThe effectiveness of nirsevimab against RSV-associated hospitalization was 91% in NVSN and \n98% in VISION ; effectiveness against any medically attended RSV -associated ARI episode in \nNVSN was 89%, and effectiveness against RSV -associated ED visits was 77% in VISION.  \nThese estimates are consistent with studies in Europe.  Longer follow up time is needed to \ndetermine duration of protection.  There has been to far limited impact on RSV hospitalization burden, likely because of late administration.  Substantial decreases in RSV-associated \nhospitalizations in young infants reported in Spain, Luxembourg, and Italy with early \nimplementation and high coverage.  It has not been possible to estimate maternal RSV vaccine \neffectiveness during the 2023-24 season due to limited uptake of maternal RSV vaccine, early \nonset of the 2023-2024 RSV season, and timing of the vaccine rollout; CDC will continue to \nmonitor maternal RSV vaccine effectiveness in future seasons . \n44 \n \n  \n  \n  \n \n \n \n  \n \n \n \n  \n \n \n \n \n  \n  \n  \n  \n \n \n \n   \n   \n \n  \n   \n \n   \n \n   \n  \n  \n \n The work group found that the available evidence shows nirsevimab to be highly effective, but \nthe duration of protection from nirsevimab and maternal vaccination remains unknown.  A \nnumber of important studies are needed for 2024-25 season and future RSV seasons , of \nmaternal vaccine effectiveness; nirsevimab effectiveness with longer follow up time, which \nshould be available with earlier widespread availability; n irsevimab effectiveness among \nchildren aged 8– 19 months with increased risk for severe disease during their second RSV \nseason; and the impact on RSV burden when nirsevimab and maternal vaccine are given with \nearlier administration and potentially increased uptake. \nOn the subject of revaccination during subsequent pregnancies, Dr. Jones reminded the \ncommittee that ACIP recommendations for Pfizer RSV maternal vaccine state that “Currently, no data are available on either the efficacy of the first lifetime dose to protect infants born after subsequent pregnancies or the safety of additional doses given during subsequent pregnancies. \nAdditional data are needed to determine whether additional seasonal doses during subsequent \npregnancies are indicated, and ACIP might update recommendations in the future, as data become available.”  There s till are no data on additional RSV vaccine doses in subsequent \npregnancies and there are potentially people who received an RSV vaccine during pregnancy for the 2023 -24 RSV season who could have a subsequent pregnancy during the 2024-2025 \nRSV season.  The work group found it concerning that data in older adults suggest that revaccination does not restore antibody levels to those after first dose.  Antibody levels are particularly important for maternal vaccination since infants are protected through transplacental transfer of antibodies.  The work group also noted that RSV vaccine differs from Tdap vaccine; maternal RSV vaccine has a potential safety concern for preterm birth and hypertensive \ndisorders of pregnancy , and an alternative product, nirsevimab, exists that can protect infants \nfrom severe RSV for subsequent pregnancies . The work group concluded that additional data \nare needed prior to recommending RSV vaccine during each pregnancy (i.e., during subsequent pregnancies) , including antibody data in pregnant people and infants with vaccination during \nsubsequent pregnancies ; safety data (e.g., reactogenicity) with vaccination during subsequent \npregnancies ; and safety data of RSV vaccine during the first pregnancy it is administered, \nparticularly regarding outcomes of preterm birth and hypertensive disorders of pregnancy . \nThe final topic on the agenda was an introduction of the ACIP Human Papillomavirus (HPV) Vaccines Work Group, from work group chair, Dr. Oliver Brooks.  Dr. Brooks reminded the committee of the evolution of HPV vaccine recommendations in the U.S., starting in 2006, with the initial recommendation for use in females at 11 or 12 year s, or as early as age 9 years, with \ncatch-up vaccination through age 26 years, using a three-dose schedule. In 2011, the \nrecommendation was extended to males, with catch -up vaccination through age 21 years. In \n2015, the schedule was changed to 2 doses for those receiving the first dose before age 15 years, and in 2019, catch-up was harmonized through age 26 years, and vaccination was \nrecommended for some adults 27 through 45 years of age with shared clinical decision-making. \nOver this time period, the U.S. transitioned from using the 4- and 2-valent HPV vaccines to \nusing the 9- valent HPV vaccine. The HPV Vaccines work group wi ll consider the number of \ndoses in the recommended HPV vaccination series; the wording of the age for routine \nvaccination; and guidance regarding persons in the “shared clinical decision-making” age range \n(27-45 years).  T here is accumulating evidence on efficacy of HPV vaccination with fewer \ndoses .  In 2022, the World Health Organization recommended a two-dose schedule for persons \naged 9 years or older and, as an off-label option, a single-dose schedule can be used for those aged 9– 20 years.  For the wording of the age for routine HPV vaccination, there is support \namong some stakeholders for starting vaccination at age 9 years, which is consistent with current ACIP recommendations, but there is thought that modification of wording could all ow \nmore flexibility.  \n45 \n \n   \n  \n   \n \n \n \n   \n  For the guidance regarding persons in the “shared clinical decision-making” age range, this \nrecommendation was made in 2019, and there’s interest in providing more guidance for \nsubgroups in this age range. The first meeting of the work group is planned for July 2024, and \nthe work group expects to present on the number of doses in the HPV vaccination schedule and the routine age recommendation wording at the October 2024 ACIP meeting. \nWith no additional business posed, the June 2024 ACIP meeting was officially adjourned. \n46 \n \n   \n   \n \n  \n \n \n \n \n  \n \n  \n \n \n \n \n \n  \n  \n \n \n \n \n  \n \n  \n \n \n \n  \n  \n \n \n \n \n \n \n \n \n \n  \n \n  \n   \n  \n  \n \n  \n  ACIP MEMBERSHIP ROSTER \nCHAIR \nTALBOT, Hel\nen Keipp, MD \nProfessor of Medicine \nVanderbilt University Nashville, TN \n3/5/2024 – 6/30/2025 \nEXECUTIVE SECRETARY \nWHARTON, Melinda, MD, MPH \nNational Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention Atlanta, GA \nMEMBERS \nBROOKS, Oliver, MD, FAAP Chief Medical Officer Watts HealthCare Corporation Los Angeles, CA Past President, National Medical Association Term: 7/26/2021 – 6/30/2025 \nCHEN, Wilbur H, MD, MS, FACP, FIDSA Professor of Medicine Center for Vaccine Development and Global Health University of Maryland School of Medicine \nBaltimore, MD \nTerm: 12/23/2020 – 6/30/2024 \nCINEAS, Sybil, MD, FAAP, FACP Associate Professor of Medicine, \nPediatrics, and Medical Science \n(Clinical) The Warren Alpert Medical School of Brown University Associate Program Director Brown Combined Residency in \nInternal Medicine and Pediatrics \nProvidence, RI Term: 9/28/2021 – 6/30/2025 \nDALEY, Matthew F, MD \nSenior Investigator \nInstitute for Health Research, Kaiser Permanente Colorado  Associate Professor of Pediatrics University of Colorado School of Medicine Aurora, CO Term: 1/4/2021 – 6/30/2024 \n47 \n \n  \n \n \n \n  \n \n \n  \n   \n  \n  \n  \n \n \n \n \n  \n \n  \n  \n \n  \n \n \n  \n \n \n \n  \n \n \n \n \n \n \n \n  \n \n \n \n \n \n  \n \n \n \n \n \n \n  JAMIESON, Denise J., MD, MPH \nVice President for Medical Affairs \nDean, Carver College of Medicine \nUniversity of Iowa \nTerm: 3/4/2024 – 6/30/2027 \nKOTTON, Camille Nelson, MD, FIDSA, FAST \nClinical Director, Transplant and Immunocompromised Host Infectious Diseases Infectious Diseases Division, Massachusetts General Hospital Associate Professor of Medicine, Harvard Medical School \nBoston, MA \nTerm: 12/23/2020 – 6/30/2024 \nLOEHR, Jamie, MD, FAAFP \nOwner, Cayuga Family Medicine \nIthaca, New York \nTerm: 7/26/2021 – 6/30/2025 \nLONG, Sarah S, MD \nProfessor of Pediatrics \nDrexel University College of Medicine Section of Infectious Diseases \nSt. Christopher’s Hospital for Children \nPhiladelphia, Pennsylvania Term: 12/24/2020 – 6/30/2024 \nMALDONADO, Yvonne (Bonnie), MD \nSenior Associate Dean for Faculty Development and Diversity \nTaube Endowed Professor of Global Health and Infectious Diseases Professor of Pediatrics and of Epidemiology and Population Health Interim Chair, Department of Medicine Stanford University School of Medicine Medical Director, Infection Prevention and Control and Attending Physician \nLucile Packard Children’s Hospital at Stanford \nDepartment of Pediatrics Palo Alto, CA Term: 3/4/2024 – 6/30/2027 \nSCHECHTER, Robert, MD, MSc Chief, Immunization Branch California Department of Public Health Richmond, CA Term: 3/6/2024 – 6/30/2027 \nSHAW, Albert C., MD, PhD, FIDSA Professor of Medicine Section of Infectious Diseases Yale School of Medicine New Haven, Connecticut \nTerm: 3/4/2024 – 6/30/2027 \n48 \n \n  \n \n  \n  \n  \n  \n  \n \n \n  \n  \n \n   \n \n \n \n  \n \n  \n \n \n  \n \n \n \n \n  \n \n \n  \n \n  \n \n \n \n \n \n  \n  \n  \n \n  \n  \n  \n  EX OFFICIO MEMBERS \nCenters for Medicare and Medicaid Services (CMS)\nHANCE, Mary Beth Senior Policy Advisor Division of Quality, Evaluations and Health Outcomes Children and Adults Health Programs Group \nCenter for Medicaid, CHIP and Survey & Certification Centers \nfor Medicare and Medicaid Services Baltimore, MD \nFood and Drug Administration (FDA)\nKASLOW, David C., MD \nDirector, Office of Vaccines Research and Review \nCenter for Biologics Evaluation and Research (CBER) \nSilver Spring, MD \nHealth Resources and Services Administration (HRSA)\nGRIMES, Reed, MD, MPH CDR, USPHS Director, Division of Injury Compensation Programs Health Systems Bureau \nHealth Resources and Services Administration \nRockville, MD \nIndian Health Service (IHS)\nCLARK, Matthew, MD, FAAP, FACP \nPhysician \nChair, IHS National Pharmacy & Therapeutics Committee Durango, CO \nOffice of Infectious Disease and HIV/AIDS Policy (OIDP)\nOKEKE, Chinedu, MD \nChief Medical Officer \nDepartment of Health and Human Services \nWashington, DC \nNational Institutes of Health (NIH)\nBEIGEL, John, MD \nAssociate Director for Clinical Research \nDivision of Microbiology and Infectious Diseases National Institute of Allergy and Infectious Diseases (NIAID) Bethesda, MD \n49 \n \n  \n \n \n \n \n \n \n \n \n \n \n  \n \n \n \n \n \n \n  \n \n  \n  \n  \n \n  \n  \n  \n \n   \n  \n  \n \n  \n \n \n \n \n \n \n   \n \n \n \n \n  LIAISON REPRESENTATIVES \nAmerican Academy of Family Physicians (AAFP)\nMORRIS, Laura, MD, MSPH \nProfessor \nClinical Family and Community Medicine \nAssociate Program Director of Family and Community Medicine Residency \nUniversity of Missouri \nColumbia, Missouri \nAmerican Academy of Pediatrics (AAP)\nO’LEARY, Sean, MD, MPH \nProfessor of Pediatrics \nPediatric Infectious Diseases \nGeneral Academic Pediatrics \nChildren’s Hospital Colorado/ University of Colorado School of Medicine \nAmerican Academy of Pediatrics (AAP) \nRed Book Editor \nKIMBERLIN, David, MD \nProfessor of Pediatrics Division of Pediatric Infectious Diseases The University of Alabama at Birmingham School of Medicine \nBirmingham, AL \nAmerican Academy of Physician Assistants (AAPA)LÉGER, Marie -Michèle, MPH, PA-C \nSenior Director, Clinical and Health Affairs American Academy of Physician Assistants \nAlexandria, VA \nAmerican College Health Association (ACHA)\nLEE, Sara, MD \nAssistant Vice President of University Health and Counseling Services \nChief Health Officer \nCase Western Reserve University \nCleveland, OH \nAmerican College Health Association (ACHA) (alternate)\nHALBRITTER, Ashlee, MPH \nExecutive Director, Public Health and Wellbeing University of Pennsylvania Philadelphia, PA \n50 \n \n   \n  \n \n  \n  \n   \n  \n \n \n  \n  \n \n \n  \n  \n \n \n  \n  \n   \n \n \n \n \n  \n  \n \n \n   \n  \n  \n  \n \n  \n \n  \n \n  \n \n \n  \n  \n \n \n \n \n American College of Nurse Midwives (ACNM) \nHAYES, Carol E., CNM, MN, MPH \nLead Clinician Clinical Quality Compliance and Management Planned Parenthood Southeast Atlanta, GA \nAmerican College of Nurse Midwives (ACNM) (alternate) \nMEHARRY, Pamela M., PHD, CNM \nMidwifery Educator, Human Resources for Health \nIn partnership with University of Rwanda and University of Illinois, Chicago \nAmerican College of Obstetricians and Gynecologists (ACOG)\nSWAMY, Geeta K., MD \nAssociate Vice President for Research \nVice Dean for Scientific Integrity \nHaywood Brown, MD Distinguished Professor of Women’s Health \nDuke University \nDurham, NC \nAmerican College of Physicians (ACP) \nGOLDMAN, Jason M , MD, FACP \nAffiliate Assistant Professor of Clinical Biomedical Science, Florida Atlantic University, Boca \nRaton, Florida Private Practice Coral Springs, FL \nAmerican Geriatrics Society (AGS) \nSCHMADER, Kenneth, MD \nProfessor of Medicine-Geriatrics Geriatrics \nDivision Chief Duke University and Durham VA Medical Centers Durham, NC \nAmerica’s Health Insurance Plans (AHIP)\nGRUBB, Jessica, MD \nMedical Director, Infectious Diseases \nElevance Health Companies/Carelon \nCharleston, SC \nAmerican Immunization Registry Association (AIRA)\nCOYLE, Rebecca, MSEd \nExecutive Director, AIRA \nWashington, DC \nAmerican Immunization Registry Association (AIRA) (alternate) \nLONDO, Courtnay, MA \nSenior Program Manager \nWashington, DC \n51 \n \n  \n  \n \n \n  \n  \n  \n  \n  \n \n \n \n  \n \n \n  \n \n \n \n  \n \n  \n \n \n \n  \n   \n    \n \n  \n \n  \n \n \n \n \n \n  \n  \n \n \n \n \n \n  \n  \n  \n   \n  \n  American Medical Association (AMA)\nFRYHOFER, Sandra Adamson, MD \nAdjunct Associate Professor of Medicine Emory \nUniversity School of Medicine Atlanta, GA \nAmerican Nurses Association (ANA)\nRESNICK, Barbara, PhD, RN, CRNP, FAAN, FAANP \nProfessor, Organizations Systems and Adult Health \nUniversity of Maryland, Baltimore \nBaltimore, MD \nAmerican Osteopathic Association (AOA) \nMAHMOUDI, Massoud, DO, PhD, MS \nPresident, American Osteopathic College of Allergy and Immunology Clinical Professor, Department of Medicine, Division of General Internal Medicine University of California San Francisco San Francisco, CA \nAmerican Pharmacists Association (APhA)GOODE, Jean -Venable \"Kelly\" R., PharmD, BCPS, FAPhA, FCCP \nProfessor and Director, PGY1 Community -Based Pharmacy Residency Program \nSchool of Pharmacy, Virginia Commonwealth University \nRichmond, VA \nAssociation of Immunization Managers (AIM)\nHOWELL, Molly, MPH Immunization Program Manager \nNorth Dakota Department of Health \nBismarck, ND \nAssociation for Prevention Teaching and Research (APTR) \nZIMMERMAN, Richard, MD, MPH Professor University of Pittsburgh School of Medicine Department of Family Medicine and Clinical Epidemiology \nPittsburgh, PA \nAssociation of State and Territorial Health Officials (ASTHO)\nJUTHANI, Manisha, MD \nCommissioner \nConnecticut Department of Public Health Hartford, CT \nBiotechnology Industry Organization (BIO)\nARTHUR, Phyllis A, MBA \nSenior Director, Vaccines, Immunotherapeutics and Diagnostics Policy Washington, DC \n52 \n \n    \n  \n \n \n  \n  \n  \n \n \n \n \n \n   \n \n \n \n \n \n \n \n  \n \n \n \n \n  \n  \n \n  \n  \n \n  \n  \n  \n    \n \n  \n  \n \n \n \n  \n  \n \n \n \n \n Council of State and Territorial Epidemiologists (CSTE) \nHAHN, Christine, MD \nState Epidemiologist Office of Epidemiology, Food Protection and Immunization Idaho Department of Health and Welfare Boise, ID \nCanadian National Advisory Committee on Immunization (NACI)\nTUNIS, Matthew, PhD Executive Secretary, National Advisory Committee on Immunization (NACI) \nCentre for Immunization Programs (CIP) \nPublic Health Agency of Canada, Government of Canada \nInfectious Diseases Society of America (IDSA)\nMUNOZ -RIVAS, Flor, MD, MSc \nChief and Medical Director Transplant Infectious Diseases Texas Children’s Hospital Houston, TX \nInfectious Diseases Society of America (IDSA) (alternate)\nMCAULEY, James B., DTM&H, MD, MPH \nClinical Director Whiteriver Indian Hospital Whiteriver, AZ \nInternational Society for Travel Medicine (ISTM)\nBARNETT, Elizabeth D, MD Professor of Pediatrics Boston University School of Medicine Boston, MA \nNational Association of County and City Health Officials (NACCHO)\nZAHN, Matthew, MD Medical Director, Epidemiology \nOrange County Health Care Agency \nSanta Ana, CA \nNational Association of Pediatric Nurse Practitioners (NAPNAP)\nDESHON, Dana, DNP, APRN, CPNP -PC \nOrder of Saint Francis Medical Group \nMorton Pediatrics \nMorton, IL \nNational Foundation for Infectious Diseases (NFID)\nHOPKINS, Robert H., Jr., MD, MACP \nProfessor of Internal Medicine and Pediatrics \nChief, Division of General Internal Medicine \nUniversity of Arkansas for Medical Sciences Little Rock, AR \n53 \n \n   \n  \n  \n   \n  \n \n  \n   \n  \n  \n \n  \n \n \n \n \n \n  \n   \n \n \n \n \n \n     \n  \n   \n    \n  \n  \n  \n    \n  \n \n \n  \n \n \n \n \n \n  \n \n \n \n  National Foundation for Infectious Diseases (NFID) (alternate) \nDALTON, Marla, PE, CAE \nExecutive Director & CEO National Foundation for Infectious Diseases (NFID) Bethesda, MD \nNational Medical Association (NMA) \nWHITLEY -WILLIAMS, Patricia, MD Professor a nd Chair \nUniversity of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School \nNew Brunswick, NJ \nPediatric Infectious Diseases Society (PIDS) \nPAULSEN, Grant, MD \nAssociate Professor of Pediatrics \nPediatric Infectious Diseases \nCincinnati Children’s Hospital Medical Center \nCincinnati, OH \nPediatric Infectious Diseases Society (PIDS) (alternate)\nROSS, Shannon A, MD, MSPH \nProfessor of Pediatrics Birmingham School of Medicine \nUniversity of Alabama \nBirmingham, AL \nPharmaceutical Research and Manufacturers of America (PhRMA) \nROBERTSON, Corey, MD, MPH  \nSenior Director, US Medical, Sanofi Pasteur \nSwiftwater, PA \nSociety for Adolescent Health and Medicine (SAHM)\nMIDDLEMAN, Amy B, MD, MSEd, MPH \nProfessor of Pediatrics Chief, Section of Adolescent Medicine University of Oklahoma Health Sciences Center Oklahoma City, OK \nSociety for Healthcare Epidemiology of America (SHEA)\nMEHROTRA, Preeti, MD, MPH \nSenior Medical Director \nInfection Control/Hospital Epidemiology \nBeth Israel Deaconess Medical Center Adult and Pediatric Infectious Diseases Harvard Medical School Boston, MA \n54 \n \n  \n \n \n \n \n \n \n \n Society for Healthcare Epidemiology of America (SHEA) (alternate)\nDREES, Marci, MD, MS \nChief Infection Prevention Officer & Hospital Epidemiologist \nChristianaCare Wilmington, DE Associate Professor of Medicine Sidney Kimmel Medical College at Thomas Jefferson University Philadelphia, PA \n55", "summary": "MEETING OF THE ADVISORY  COMMITTEE ON IMMUNIZATION  PRACTICES (ACIP)  JUNE 26-28, 2024  MEETING SUMMARY  Trade names are used for identification purposes only and do not indicate endorsement.                                                                                                                                                                     WEDNESDAY: JUNE 26 , 2024  WELCOME AND INTRODUCTIONS  Call to Order  Dr. Keipp Talbot, ACIP Chair, called to order and presided over the June…", "source_url": "https://www.cdc.gov/acip/meetings/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/minutes/summary-2024-06-26-28-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "minutes", "tags": ["acip", "cdc", "vaccines", "minutes"], "page_count": 55}
{"title": "agenda 2024 02 28 29 508", "content": "Final - February 26, 2024\nDr. Melinda Wharton (ACIP Executive Secretary, CDC)\nDr. Matt Daley (ACIP, WG Chair)\nDr. Christopher Taylor (CDC/NCIRD)\nDr. Kevin Chatham-Stephens (CDC/NCIRD)\nDr. Ruth Link-Gelles (CDC/NCIRD)Dr. Lisa Prosser (University of Michigan)Dr. Megan Wallace (CDC/NCIRD)Dr. Lakshmi Panagiotakopoulos (CDC/NCIRD)8:30 COVID-19 Vaccines\nIntroduction\nCOVID-19-associated hospitalizations among adults - COVID-NET \nCOVID-19 vaccination coverage updateCOVID-19 vaccine effectiveness Economic analysis of an additional dose of COVID-19 vaccineEvidence to Recommendations Next steps for the COVID-19 vaccine program\n10:50 Break \n11:10 Chikungunya VaccinesIntroductionUpdate on chikungunya vaccine licensure Review of proposed policy options for chikungunya vaccine use \namong U.S. adults traveling abroad\nReview of proposed policy options for chikungunya vaccine use \namong laboratory workers\nVaccine use among pregnant and breastfeeding women Dr. Wilbur Chen (ACIP, WG Chair)\nDr. Susan Hills (CDC/NCEZID)Dr. Susan Hills (CDC/NCEZID)\nDr. Susan Hills (CDC/NCEZID)Dr. Susan Hills (CDC/NCEZID), Dr. Dana Meaney-Delman \n(CDC/NCBDDD)\n12:25 Break\n1:25 DT Vaccine \nGuidance to use Td vaccine for those instances when receipt of the \npertussis component is contraindicatedDr. Michelle Hughes (CDC/NCIRD)\nDr. Jeanne Santoli (CDC/NCIRD)\n1:35 Break\n1:40 Public Comment \n2:00 VOTES COVID-19 Vaccines Chikungunya VaccineVFC VOTESDiphtheria, Tetanus, and Pertussis \nDr. Megan Wallace (CDC/NCIRD)Dr. Susan Hills (CDC/NCEZID)\nDr. Jeanne Santoli (CDC/NCIRD)\n2:30 Break\n2:40 Influenza Vaccines \nIntroduction\nInterim Estimates of 2023–24 Seasonal Influenza Vaccine \nEffectiveness\nInterim Influenza Vaccine Effectiveness Against Laboratory-\nConfirmed Influenza in California, October 2023—January 2024\nSafety of LAIV4 in Children with Asthma\nInfluenza B/Yamagata Update                Dr. Jamie Loehr (ACIP, WG Chair)\nDr. Aaron Frutos (CDC/NCIRD/ID)\nDr. Sophie Zhu (California Department of Public Health \nand CDC/PHIC/DWD)\nDr. C. Buddy Creech (Vanderbilt University Medical \nCenter)\nDr. Lisa Grohskopf (CDC/NCIRD/ID)\n4:10 Break\n4:20 Polio Vaccines\nWork Group deliberations on potential use of nOPV2 as an outbreak \ncontrol measure in the US\nClinical considerations for children who received fractional dose \ninactivated polio vaccine (fIPV)  in other countriesDr. Sarah Kidd (CDC/NCIRD)\nDr. Sarah Kidd (CDC/NCIRD)\nCMS, FDA, HRSA, IHS, OIDP, NIH 5:10 Agency Updates \n5:30 AdjournMEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)\nCenters for Disease Control and Prevention\nAtlanta, Georgia 30329  \nFebruary 28-29, 2024\nWednesday, February 28, 2024\n8:00 Welcome & Introductions\nFinal - February 26, 2024\n8:00 Welcome & Introductions Dr. Melinda Wharton (ACIP Executive Secretary, CDC)\n8:10 Respiratory syncytial virus (RSV) Vaccines Adults\nIntroductionManufacturer presentation: Moderna safety & efficacy in adults aged\n≥60 years\nRisk-stratified rates of RSV-associated hospitalization among adults\nImplementation update: older adult RSV vaccination\nPost-marketing safety surveillance of older adult RSV vaccination\nPreliminary Analysis of Guillain-Barré Syndrome (GBS) following RSV \nVaccination among adults 65 years and older\nOlder adult RSV vaccination: benefits and risks discussion\nWork group interpretations and discussionDr. Camille Kotton (ACIP, WG Chair)\n Dr Rituparna Das (Moderna)\nDr. Rebecca Woodruff (CDC/NCCDPHP)\nDr. Carla Black (CDC/NCIRD)\nDr. Tom Shimabukuro (CDC/NCIRD)\nDr. Patricia Lloyd (FDA)\nDr. Michael Melgar (CDC/NCIRD)\nDr. Amadea Britton (CDC/NCIRD)\n11:10 Break\n11:20 Meningococcal Vaccines Introduction Revising the Adolescent Meningococcal Vaccine Schedule:  Term of \nReference and Considerations \nGSK Pentavalent MenABCWY vaccine:  Term of ReferenceDr. Jamie Loehr (ACIP, WG Chair) \nDr. Sarah Schillie (CDC/NCIRD)\nDr. Sarah Schillie (CDC/NCIRD)\n12:00 Break\n12:45 Pneumococcal Vaccines \nIntroductionCurrent epidemiology of invasive pneumococcal disease and \npneumococcal vaccine coverage in adults\nPreliminary findings of the Pneumococcal pNeumonia Epidemiology, \nUrine serotyping, and Mental Outcomes (PNEUMO) US study\nPhase 3 clinical trial data of PCV21\nPost-licensure PCV20 safety data\nPCV21 Policy Questions and Preliminary WG interpretations of EtRDr. Jamie Loehr (ACIP, WG Chair)\nMr. Ryan Gierke (CDC/NCIRD)\nDr. Wesley Self (Vanderbilt University Medical Center)\nDr. Heather Platt (Merck)\nDr. Pedro Moro (CDC/NCEZID), Dr. Richard Forshee (FDA)\nDr. Miwako Kobayashi (CDC/NCIRD)\n3:00 Break\n3:10 Combined Diphtheria and Tetanus Toxoids and Acellular Pertussis, \nInactivated Poliovirus, Haemophilus influenzae Type B Conjugate, \nand Hepatitis B vaccine (Vaxelis®) \nIntroduction\nBackground on invasive Hib disease and vaccination among American\nIndian and Alaska Native Populations\nThe HibVax Study: Immunogenicity of H. influenzae type b PRP-OMP \nvaccines in American Indian and Alaska Native infants\nWork group considerationsDr. Jamie Loehr (ACIP, WG Chair)\n Dr. Jennifer Collins (CDC/NCIRD)\nDr. Laura Hammitt (Johns Hopkins Bloomberg School of \nPublic Health - Center for Indigenous Health)\nDr. Jennifer Collins (CDC/NCIRD)\n4:30 AdjournThursday, February 29, 2024\nFinal - February 26, 2024\nAcronyms\nCDC Centers for Disease Control and Prevention\nCMS Centers for Medicare and Medicaid Services \nCOVID-19 Coronavirus disease 2019\nEtR Evidence to Recommendations Framework\nFDA Food and Drug Administration\nGRADE Grading of Recommendations Assessment, Development and Evaluation\nHRSA Health Resources and Services Administration\nIHS Indian Health Service\nNCHHSTP National Center for HIV, Hepatitis, STD and TB Prevention\nNCIRD National Center for Immunization & Respiratory Diseases\nNCEZID National Center for Emerging and Zoonotic Diseases \nNIAID National Institute of Allergy and Infectious Diseases\nOIDP Office of Infectious Disease and HIV/AIDS Policy\nSARS-CoV-2 Severe Acute Respiratory Syndrome Coronavirus 2\nWG Work Group\nWHO World Health Organization\nVE Vaccine Effectiveness", "summary": "Final - February 26, 2024 Dr. Melinda Wharton (ACIP Executive Secretary, CDC) Dr. Matt Daley (ACIP, WG Chair) Dr. Christopher Taylor (CDC/NCIRD) Dr. Kevin Chatham-Stephens (CDC/NCIRD) Dr. Ruth Link-Gelles (CDC/NCIRD)Dr. Lisa Prosser (University of Michigan)Dr. Megan Wallace (CDC/NCIRD)Dr. Lakshmi Panagiotakopoulos (CDC/NCIRD)8:30 COVID-19 Vaccines Introduction COVID-19-associated hospitalizations among adults - COVID-NET  COVID-19 vaccination coverage updateCOVID-19 vaccine effectiveness…", "source_url": "https://www.cdc.gov/acip/meetings/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/agendas/agenda-2024-02-28-29-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "agendas", "tags": ["acip", "cdc", "vaccines", "agendas"], "page_count": 3}
{"title": "summary 2024 02 28 29 508", "content": "MEETING OF THE ADVISORY \nCOMMITTEE ON IMMUNIZATION \nPRACTICES (ACIP) \nFEBRUARY 28-29, 2024 \nMEETING SUMMARY \nTrade names are used for identification purposes only and do not indicate endorsement. \n \n   \n \n  \n \n \n \n   \n     \n \n  \n  \n   \n  \n      \n     \n    \n   \n \n  \n \n   \n \n  \n   \n  \n \n \n  \n \n \n \n    \n     \n \n   \n     \n     \n   \n    \n  \n \n  \n   \n  \n \n  WEDNESDAY: FEBRUARY 28, 2024 \nWELCOME AND INTRODUCTIONS \nCall to Order/Roll Call \nDr. Melinda Wharton (ACIP Executive Secretary & Acting Chair , CDC) called to order and \npresided over the February 28-29, 2024, Advisory Committee on Immunization Practices (ACIP ) \nmeeting.  She made opening announcements about the availability of presentation slides on the \nACIP website and scheduled oral public sessions as well as the written public comment process and then reviewed conflict of interest policies for ACIP members.  She announced that new ACIP members have been approved by the Department of Health and Human Services (HHS) . \nOfficial letters of invitation will be released soon to these individuals, and the ACIP looks forward \nto having them join a future ACIP meeting. As allowed under the ACIP charter, the ACIP’s six \nEx O fficio members were temporarily designated as voting members. Dr. Wharton noted that \nduring role call and prior to the votes, she would ask that the Ex O fficio members state any \nconflicts of interest (COIs). She also announced that because the process for the new ACIP \nChair to join the committee had not yet been completed, she would be chairing the meeting. \nShe then conducted a roll call , which established that a quorum was present. A list of Members, \nEx Officios , and Liaison Representatives is included in the appendixes at the end of this \nsummary document. The following COIs were identified for the first day of this meeting: \nDr. Chen is working with MassBiologics on a diarrhea therapeutic product that is funded by \nthe Bill and Melinda Gates Foundation. MassBiologics is a non-profit vaccine manufacturer \nassociated with the University of Massachusetts Chan Medical School and maker of a \ndiphtheria/ tetanus (DT) vaccine. Because this meeting will include a vote on the addition of \nDT to the Vaccines for Children ( VFC) program, he indicated that he would recuse himself \nfrom the VFC vote for that vaccine. \nCOVID -19 VACCINES \nDr. Matthew F. Daley introduced this session on behalf of the ACIP COVID -19 Vaccines Work \nGroup. To review current COVID -19 vaccine policy, the ACIP m et on September 12, 2023, to \nreview the available evidence for the updated 2023 -2024 formula of COVID-19 vaccines. At that \ntime, ACIP recommended an updated COVID -19 vaccine as authorized under Emergency Use \nAuthorization (EUA) or approved by a Biologics License Application (BLA) in persons aged ≥6 \nmonths of age. This included Moderna COVID -19 vaccine in persons ≥6 months of age, Pfizer -\nBioNTech COVID -19 vaccine in persons ≥6months of age, and Novavax COVID-19 vaccine in \npersons ≥12 years of ager. The recommendation also included a recommendation that \neveryone ≥5 years of age get an updated dose of the 2023-2024 formula to protect against \nserious illness from COVID -19 regardless of prior vaccination or infection history. Children 6 \nmonths –4 years of age were recommended to receive multiple doses of COVID -19 vaccines to \nbe up to date, including at least 1 dose of updated COVID -19 vaccine. Additional \nrecommendations were made for those who are moderately or severely immunocompromised, \nwho may get additional doses of updated COVID -19 vaccine. \n2 \n \n     \n  \n   \n \n \n   \n \n     \n     \n   \n \n    \n   \n \n      \n  \n  \n   \n \n  \n   \n        \n  \n    \n  \n  \n   \n  \n   \n \n \n   \n     \n \n  \n    \n  \n \n    \n  \n   \n       \n   \n      \n \n  Dr. Christopher Taylor (CDC/NCIRD) reported on data from the COVID -19-Associated \nHospitalization Surveillance Network (COVID -NET ). COVID -NET collects data from more than \n300 acute-care hospitals in 98 counties across 13 states , includ ing about 10% of the U nited \nStates (US) population. Hospitalizations reported to COVID -NET include all those for which a \npositive SARS -CoV -2 test result was reported within 14 days prior or during hospitalization. \nScreening for SARS- CoV-2 is driven by clinical judgment and facility policies. \nThe majority (67%) of hospitalizations captured in COVID -NET between October 2023– January \n2024 were among adults ≥65 years of age. Adults ≥75 years of age comprised 46% of \nhospitalizations. Among adults ≥75 years of age during October 2022– November 2023, 25% of \nCOVID -19-associated hospitalizations were residents of a long-term care facility (LTCF) at the \ntime of admission. Among all adults hospitalized with COVID -19 for the period October \n2022─ November 2023, 3.8% died in -hospital. Among those, 1.4% were 18─ 49 years of age. \nThe highest proportions of in-hospital deaths occurred among adults ≥65 years of age, with \n5.5% of adults 65─ 74 years of age and 4.4% ≥75 years of age dying in-hospital. Among adults \nages ≥65 years of age who died in-hospital, 28% were residents of LTCFs. An examination of \ndeath certificate data from March 2020– April 2022 found that among all deaths in adults with \nCOVID -19-associated hospitalization, 67% occurred in-hospital and 33% occurred ≤30 days \npost-discharge. The proportion of deaths occurring post-disch arge increased with age. \nFor the period October 2022─ November 2023, 16% of all adults hospitalized with COVID -19 \nhad an immunocompromising condition. These percents varied by age, ranging from 12% or 1 \nin 8 adults 18─ 49 years of age to 21 % in adults 65─74 years of age with an \nimmunocompromising condition. Looking at the proportion of COVID -19-associated \nhospitalizations among adults by immunocompromised status overall and by intervention or \noutcome for the period October 2022 ─November 2023, 16% of all COVID -19-associated \nhospitalizations were among persons with an immunocompromising condition. Among those \nadmitted into the ICU, 17% had an immunocompromising condition and 28% of those who died \nin-hospital had an immunocompromising condition. The most common underlying conditions \nobserved among hospitalized adults varied by age group. \nData pertaining to COVID -19-associated hospitalizations by vaccination status among adult age \ngroups were limited to October ─November 2023, given that they were the 2 months of data \navailable for the updated 2023-2024 monovalent dose. Overall , no more than 5% of hospitalized \nadults in any age category received the updated 2023-2024 monovalent dose. The largest \nproportion of hospitalized adults who received the updated monovalent dose was adults ≥65 \nyears of age at 5% . It is important to note that these 2 months of data are preliminary data and \nthat continued examination of these data is ongoing. \nDr. Kevin Chatham -Stephens (CDC/NCIRD) presented COVID -19 vaccination coverage data \nand attitudes and experiences regarding COVID -19 vaccination. According to CDC’s National \nImmunization Survey (NIS), among adults overall, 21.9% reported being up-to-date, with a \nrange from 43.5% among adults ≥75 years of age down to 9.5% among adults 18 ─29 years of \nage. Among children overall, 12.2% were reported to be up-to-date, with the range from 15.8% \namong those 12─ 17 years of age down to 5.9% among those 6 months ─4 years of age. \n3 \n \n     \n  \n \n    \n    \n    \n    \n   \n   \n \n  \n    \n    \n    \n    \n \n   \n  \n \n \n   \n \n  \n   \n   \n   \n \n \n \n    \n \n \n   \n     \n    \n   \n     \n   \n      \n \n    \n  \n   \n    \n      \n  \n   \n   \n  COVID -19 vaccine coverage among adults varied by jurisdiction , ranging from 9.5% in Puerto \nRico and 10.5% in Mississippi to 41.9% in the District of Columbia ( DC). In terms of COVID-19 \nvaccination status and intent among adults ≥18 years of age, the percent of adults who were \nvaccinated with the 2023-2024 COVID -19 vaccine gradually rose from about 3% percent in late \nSeptember 2023 to 21.9 % as of February 3, 2024. The percent of adults reporting they definitely \nwill get vaccinated decreased from 28.2% to 11.3%. The percent of adults reporting they \nprobably will get vaccinated or are unsure if they will get vaccinated has remained relatively \nstable between approximately 27% to 32%. The percent reporting they probably or definitely will \nnot get vaccinated has also remained relatively stable between 37% to 42%. \nCoverage also varied by race/ethnicity, with coverage highest amongst white non-Hispanic \nadults at 24.4% and lowest among American Indian/ Alaska Native (AI/AN) adults at 11.4% , \nNative Hawaiians and Other Pacific Islanders (NH/OPI) at 14.1%, and Hispanic adults at 13.3 %. \nCoverage by urbanicity was lower in rural areas at 16.8% than coverage in suburban and urban \nareas at 21.3% and 29.9%, respectively. Adults with health insurance at 22.7% percent had \nhigher vaccination coverage than adults without health ins urance at 6.9 %. Coverage also varied \nby household income, with coverage increasing with increasing income. Those with incomes \ngreater than $ 75,000 had the highest coverage at 26.1% percent. Coverage did not vary based \non disability status. \nData on the percent of pregnant persons 18─ 49 years of age vaccinated with a 2023-2024 \nCOVID -19 vaccine come from the Vaccine Safety Datalink (VSD), which is a collaborative \nproject between CDC and integrative healthcare organizations and networks across the US that \nuses electronic health data from participating sites to monitor and assess the safety of vaccines. \nOverall, 12.5% of pregnant persons received an updated COVID -19 vaccine as of January 27, \n2024. Coverage ranged from 4.8% among Black N on-Hispanic persons to 21.3% among Asian \npersons. \nHow people think and feel about COVID -19 vaccines has changed since 2022. C omparing \nresults from January 2022 to results from January 2024 from the NIS , most Americans still \nconsider COVID -19 vaccines to be safe and important, but vaccine confidence has declined. \nDisease risk perception has also changed, as reflected in the percentage of Americans who are \nmoderately or very concerned about getting COVID -19. The percent of US adults who think that \na COVID -19 vaccine is very or completely safe has declined from 67.3% to 55.6% percent. The \npercent of US adults who think that a COVID -19 vaccine is somewhat or very important has \ndeclined from 83.9% to 69.6%. The percentage of US adults who are moderately or very \nconcerned about getting COVID -19 has declined from 55% to 32.7%. The percent of adults \nreporting that their health care provider ( HCP ) recommends the COVID- 19 vaccine decreased \nfrom 36.1% in May 2021 to 20.4% in January 2024. \nA survey was conducted by CDC, RAND, and the University of Iowa of HCP in February 2023 \nthat involved a panel of HCP comprised of all physician specialties and other health-related \nprofessions, such as nurses and pharmacists. Based on results for physicians who spend at \nleast half of their time in outpatient primary care where vaccines are administered in their \nworksite, most physicians reported that they always recommend bivalent boosters , with the \nhighest percentage being for patients ≥65 years of age at 80.9%. Regarding the reasons HCP \n(e.g., physicians, nurses, pharmacists) reported for not recommending the COVID-19 bivalent \nboosters to eligible patients , the most common response was a medical reason. That was \nfollowed by patients will refuse booster vaccination, patients are tired of hearing about COVID-\n19 vaccines, and there is a high level of vaccine resistance in the community. \n4 \n \n    \n   \n \n \n \n  \n  \n  \n \n   \n  \n   \n \n \n  \n  \n  \n   \n \n \n  \n \n \n   \n       \n       \n \n  \n \n \n \n   \n   \n  \n \n  \n  \n \n   \n  \n  \n  \n \n  \n  \n   \n      Potential reasons for primary care providers (PCP) to not stock COVID -19 vaccines included \nperceived low interest for COVID -19 vaccination in the patient population, c ost of the COVID -19 \nvaccine and other associated vaccination costs , their healthcare system decided to not stock \nthe COVID -19 vaccines, and availability of the COVID -19 vaccines elsewhere in the community \n(e.g., pharmacies). \nBased on data from the Omnibus Surveys between November 30─ December 21, 2023 on the \nacceptability of co-administration of influenza, COVID -19, and RSV vaccines, respondents were \nasked, “If you were due for them and they were offered, would you get more than one of these \nvaccines in the same visit: COVID -19, flu, RSV ?” Approximately 2/3 of US adults indicated they \nwould be open to co-administration of these vaccines . \nDr. Daley asked CDR Chatham -Stephens about racial and ethnic disparities in uptake of the \n2023-2024 COVID -19 vaccine formula in the context of recognizing that low coverage overall is \nthe biggest problem. It seems like some disparities have returned and wondered if there was a \nsense of why that is. Referring to the coverage data overall he presented for adults, Dr. Chatham -Stephens \nconfirmed that there were some racial/ethnic disparities. There also have been some racial and \nethnic disparities among pregnant people. However, that is not necessarily unique to the \nCOVID -19 vaccine. Unfortunately, similar disparities have been observed with other vaccines . \nThere are likely multiple reasons for this, such as disparities in access to vaccine and access to \nhealthcare, as well as misinformation and disinformation circulating among different populations. \nSome of the disparities were mitigated to some degree during the height of the federally -\ndistributed COVID-19 vaccine program, but have begun to return. CDC is engaged in a number \nof activities to address some of these issues . \nDr. Loehr took a moment to speak to the primary care providers of the country, pointing out that \nCOVID vaccine is now just a regular vaccine like vaccines for everything else and he \nacknowledged that many people do not want it. However, since he has had it in his office, 2 or 3 \npeople a day are pleased to be able to easily get the vaccine there. Anything that can be done \nto lower the barrier of getting a vaccine in someone’ s arm is wonderful. Therefore, he treats \nCOVID vaccine like influenza and other vacci nes he offers to his patients. Some people do not \nwant it, but a lot of others are glad he has it in his office. \nRegarding Dr. Taylor’s presentation , Dr. Long said she found it difficult to interpret the slide on \nhospitalized patients and the percent who had various conditions without knowing the \npopulation at large with these conditions in the same age groups. \nDr. Taylor indicated that the work group acknowledges this as a limitation. Early in the \npandemic, an analysis was published that paired COVID-NET data from the early months of the \npandemic through June 2020 with population-level underlying conditions that were available \nthrough the Behavioral Risk Factor Surveillance System (BRFSS), which provides estimates of \nunderlying chronic conditions at a population level. That paper look ed at those risks of \nhospitalization versus the risk in the population. That analysis is being updated and is \nanticipated to be ready for presentation at the next ACIP meeting. \nDr. Brooks commented that they had received a lot of information with these excellent \npresentations , but had to figure out the synopsis. Income reduces coverage. Insurance status \nreduces coverage. Only 5% of Black pregnant women got vaccinated. Why? Lower rates among \nAfrican-Americans. He asked whether there are any data coverage in urban versus rural areas.  \n5 \n \n    \n    \n \n       \n  \n     \n    \n      \n     \n   \n  \n    \n \n     \n   \n  \n \n  \n     \n \n   \n  \n \n \n \n    \n \n   \n     \n \n \n  \n \n   \n    \n  \n     \n \n   \n   \n  \n   \n  \n      \n    \n     \n    Dr. Chatham -Stephens responded that u rban and suburban residents had 21.9% and 21.3% \npercent coverage respectively compared to rural respondents at 16.8%. \nDr. Kotton stressed how devastating it was to see how many elderly and immunocompromised \npeople are being admitted to hospital, are in the intensive care unit ( ICU), and are dying from \nCOVID -19. It was shocking to see that only 30% to 40% of higher-risk elderly and \nimmunocompromised people are getting the updated vaccine. She encouraged that during this \nmeeting, the ACIP provide clarity on the recommendation for an updated vaccine and for \nimmunocompromised individuals. In September 2023, ACIP said that they could get 2 doses of \nvaccine at least 2 months apart. However, the community needs to be provided with clarity on \nthat because people do not understand what that recommendation means. This is a life -and-\ndeath situation for many of the patients she takes care of. \nDr. Ruth Link -Gelles (CDC/NCIRD) shared CDC ’s current data on the effectiveness of updated \n2023– 2024 monovalent XBB.1.5 COVID -19 vaccine against symptomatic SARS-CoV -2 from \nseveral CDC vaccine effectiveness (VE) platforms.  \nBy July─ August 2023 just before the updated vaccines were introduced, individuals in the US \nhad high rates of infection-induced immunity that were above 70% for all age groups and almost \n90% for those 16─ 49 years of age. Infection can provide some protection from future infection. \nTherefore, VE findings should be interpreted as the incremental benefit provided by COVID -19 \nvaccination in a population with a high prevalence of infection-induced immunity. \nData from multiple systems demonstrated that updated 2023 -2024 COVID-19 vaccination \nprovided increased protection against symptomatic SARS -CoV -2 infection and COVID-19-\nassociated emergency department (ED) and urgent care (UC) visits and hospitalizations \ncompared to no updated vaccine dose. Receipt of an updated dose provided protection against \nJN.1, the most common circulating variant currently, as well as other circulating variants. These \nare relatively early estimates from all 3 VE studies , with no substantial waning. However, \nwaning is expected based on past experience with COVID -19 vaccines, and CDC will continue \nto monitor VE. \nDr. Lisa A. Prosser, University of Michigan, presented the results from an economic analysis of \nan additional dose of COVID-19 vaccine among adults . The presentation was an extension of \nan economic model that previously had been presented to the committee.  There were 2 \nupdates to the model which were to: 1) revise the probability of hospitalization from October \n2022─September 2023 to reflect more recent lower rates ; 2) adjust vaccine impact for \nseasonality ; and 3) add a new intervention strategy to include an additional dose of vaccine \napproximately 6 months following an additional dose , referred to as the 2-dose strategy. \nIncremental cost-effectiveness ratios (ICERs ) were calculated comparing an updated mRNA \nbooster 1-dose strategy to no booster, using the updated hospitalization and seasonality -\nadjusted vaccine impact inputs. This analysis also provided ICERs for the base case and \nuncertainty analyses comparing 1-dose, 2-dose, and no booster vaccination strategies. \nUpdating the model to include revised hospitalization rates and seasonality -adjusted vaccine \nimpact yield ed slightly higher ICERs for all age groups compared to the September 2023 \nanalysis. In the updated analysis, the ICER for the 1-dose strategy for adults 18─ 49 years of \nage was roughly $163,000 per QALY gained. For adults 50─64 years of age, it was about \n$80,000 per QALY gained. For individuals ≥65 years of age, 1 dose of an updated vaccine was \nno longer cost-saving but yielded an ICER of about $12,000 p er QALY . \n6 \n \n      \n     \n    \n \n   \n    \n   \n   \n   \n   \n \n \n     \n \n \n    \n     \n \n     \n \n \n    \n  \n   \n  \n  \n \n  \n      \n       \n   \n  \n     \n   \n \n \n    \n  \n    \n  \n   \n   \n    \n  \n   \n    \n   \n     \n     \n   In terms of the 2-dose strategy, the ICER was greater than $1.3 million per QALY for adults \n18─49 years of age, greater than $700,000 per QALY for adults 50─64 years of age, and great \nthan $255,000 per QALY for adults ≥65 years of age using base-case assumptions. \nVarying the probability of hospitalization had a substantial impact on the results. For probability \nof hospitalization from 2 to 4 times the base case, the incremental cost-effectiveness ratios \ndropped to about $120,000 per QALY at 2 times the base case, $65,000 per QALY at 3 times \nthe base case, and $34,000 per QALY at 4 times the base case. These higher rates correspond \nto underlying condition: chronic obstructive pulmonary disease (COPD) , history of stroke, \ncoronary artery, asthma, hypertension, obesity, diabetes, chronic kidney disease (CKD) , and \nsevere obesity. \nLower costs of vaccination also were associated with lower ICERs . Varying only the cost of the \nvaccine dose would move a 1-dose strategy into the cost-saving range for cost per dose of $20 \nor $60 per dose. The ICER for a 2-dose strategy would fall below $150,000 per QALY for a cost \nper dose of $60 or less. Varying all vaccination-related costs to lower bounds yield ed cost \nsavings for a 1-dose strategy and about $51,000 per QALY for the 2-dose strategy. \nDr. Kotton asked Dr. Prosser whether immunocompromised persons were included in the \nmodeling. Dr. Prosser indicated that immunocompromised individuals were not explicitly considered in this \nanalysis , so these results should be considered to apply to the immunocompetent population. \nSome inferences were drawn to the extent possible from the higher hospitalization rates or other \nhigher -risk scenarios that might correspond to immunocompromised population, but those were \nnot explicitly defined in that way. \nReferring to Dr. Link -Gelles’s presentation, Dr. Daley noted that there may be a perception in \nthe public that vaccines are getting less effective. Comparing the news of November 8, 2020, \nwhen they heard that these vaccines were 94% to 95% percent effective, 50% effectiveness is \nnot that compelling. As D r. Link -Gelles has explained, those are completely different because \nnow the vaccinated have a history of multiple vaccines plus infection and the unvaccinated \ncomparison group has some immunity. He wondered how to convey that 50% VE in this context \nstill prevents negative outcomes, such as hospitalizations and deaths. \nDr. Link -Gelles emphasized the importance of the context. Early in the pandemic, most of the \npopulation had yet to be infected and had received zero doses of vaccine collectively. The \nvaccine had the opportunity to protect almost absolutely, which was reflected in the clinical trials \nwith VE in the 90% range. There was nowhere to go but up in terms of collective immunity from \nCOVID -19. At this point in the pandemic, most people in the population have been infected. \nAdding the people who have been vaccinated and not infected reaches about 98% who have \nsome type of prior immunity from infection, vaccination, or both. That provides protection \nagainst future infection and future severe disease, but it does not protect absolutely. In that \ncontext, vaccines are now providing an incremental or extra benefit beyond whatever benefit someone has remaining from their past infection or past vaccination. It is known that protection \nwanes from past vaccination and past infection. Over time, whether someone has been infected \nor vaccinated multiple times, their protection will decrease. Vaccines can then provide important \nextra protection in terms of boosting whatever protection one has. That is important for all \npeople in the US, especially those who are at the highest risk such as pregnant people, people \nwith high-risk conditions, and individuals ≥65 years of age. \n7 \n \n   \n    \n \n \n \n \n \n    \n     \n    \n \n    \n \n \n  \n \n   \n     \n  \n \n \n \n  \n \n \n   \n  \n \n  \n  \n     \n \n     \n   \n \n  \n \n  \n   \n \n \n \n   \n  \n  \n   \n \n Even in the context of prior infection and prior vaccination, people are getting infected, being \nhospitalized, having critical illness , and dying. The vaccine gives them extra protection, \nparticularly those who have high-risk conditions . \nDr. Long asked whether the 50% of the population with a lowered chance of being hospitalized \nwere used in the cost-effectiveness model . \nDr. Link -Gelles clarified that the estimates from the cost-effectiveness model came from the IVY \nand VISION Networks. While those data were slightly older data, they were essentially the same \nand c ost-effectiveness of the booster was reasonable. \nDr. Megan Wallace (CDC/NCIRD) presented the Evi dence to Recommendations (EtR) \nFramework for the policy question, “Should persons ages 65 years and older be recommended \nfor an additional dose of 2023-2024 formula COVID -19 vaccine?” The additional dose should be \nat least 4 months after receipt of the previous updated COVID-19 vaccine dose. As a reminder, \nthe currently authorized and approved 2023-2024 formula COVID -19 vaccines include Moderna, \nNovavax, and Pfizer-BioNTech vaccine. This policy question would apply to all 3 of these \nvaccines. ACIP recommended the 20 23-2024 formula COVID -19 vaccine in September 2023. \nThis session focused on whether an additional dose should be recommended in older adults \nthis year. \nThere are already recommendations for additional doses of the 2023-2024 formula COVID -19 \nvaccine among people who are moderately or severely immunocompromised, who have the \noption to receive 1 additional dose of updated COVID-19 vaccine at least 2 months following the \nlast recommended updated COVID -19 vaccine dose. Further additional doses may be \nadministered, informed by the clinical judgment of a healthcare provider and personal \npreference and circumstances. Any further additional doses should be administered at least 2 \nmonths after the last updated COVID -19 vaccine dose. \nTo summarize the public health problem, COVID -19 hospitalizations peaked in late December \n2023─ early January 2024. However, there are still approximately 20,000 new hospital \nadmissions and 2,000 deaths due to COVID -19 each week. Persons ≥65 year of age have the \nhighest COVID -19 hospitalization rates, and hospitalization rates within this age group increase \nwith increasing age. Persons ≥75 years of age have the highest COVID -19 mortality rates. \nImmunosenescence and higher prevalence of vaccine-only immunity in older adults compared \nto younger adults suggest that more frequent doses may be needed to maintain protection in this population. While there are increases in COVID -19 during respiratory virus season, COVID -\n19 hospitalizations and deaths continue throughout the year due to ongoing circulation of SARS- CoV-2. Inequities in COVID -19 hospitalizations by race and ethnicity continue and should \nbe considered in the context of an age-based recommendation. The work group agreed that \nCOVID -19 disease among persons ≥ 65 years of age is of public health importance. \nFor benefits and harms, Dr. Wallace summarized evidence that 2023-2024 formula COVID -19 \nvaccination provided increased protection against symptomatic SARS -CoV -2 infection and \nCOVID -19-associated ED/UC visits and hospitalizations compared to no updated vaccine dose. \nCOVID -19 VE from previous vaccine formulations has waned over time but appears more \ndurable against critical illness. An additional dose of 2023-2024 formula may restore VE, which \nis expected to wane, providing additional protection until the next updated vaccine is available. COVID -19 vaccines have a favorable safety profile. Local and systemic symptoms have been \nreported following receipt of COVID -19 vaccines. However, symptoms are less frequent and \nsevere among older adults compared with adolescents and younger adults. \n8 \n \n   \n  \n  \n    \n  \n  \n \n    \n \n    \n \n   \n    \n   \n      \n     \n \n  \n  \n \n \n    \n  \n  \n  \n    \n  \n  \n   \n  \n   \n \n \n  \n \n \n \n \n \n  \n  \n \n   \n    \n   \n  \n The available data do not provide clear and consistent evidence of a safety issue for ischemic \nstroke with bivalent mRNA COVID -19 vaccines, either when given alone or when given \nsimultaneously with influenza vaccines. The work group determined that the desirable \nanticipated effects were moderate and that the undesirable anticipated effects were small. A \nminority of work group members were of the opinion that the undesirable anticipated effects were minimal. The work group felt that the desirable effects outweigh the undesirable effects. \nFor the values domain , adults ≥65 years of age were more concerned about COVID -19 disease \nand had higher confidence in vaccine safety and vaccine importance than those < 65 years of \nage. Black adults were more concerned about COVID -19 disease than people of other racial \nand ethnic groups. Confidence in COVID -19 vaccine safety and importance varied by race and \nethnicity. Half of adults reported that they planned to take precautions because of COVID-19 \nduring the f all and winter months, with 41% of adults ≥65 years of age and older planning to \navoid large gatherings. Larger proportions of Black and Hispanic adults reported that they \nplanned to take precautions against COVID -19 than w hite adults. The work group’s opinion was \nthat older adults feel that the desirable effects are large compared to the undesirable effects. \nRegarding whether there is important uncertainty about, or variability in, how older adults value the main outcomes, the majority opinion of the work group was that there probably is important \nuncertainty or variability, and the minority opinion was that there is probably no important \nuncertainty or variability. \nThe vaccine coverage data presented provided evidence to support acceptability.  As of \nFebruary 2024, vaccination coverage with the 2023-2024 COVID -19 vaccine was highest \namong older adults 65─74 years of age and ≥75 years of age compared to younger age groups. \nDisparities in COVID -19 vaccine coverage have been observed across many demographic \nfactors, including race, ethnicity, insurance status, and rurality. Adults who were vaccinated or definitely plan to get vaccinated were more likely to report that a healthcare provider recommended that they get a COVID -19 vaccine. Adults ≥65 years of age were more likely to \nreport HCP recommendation than younger adults. Among adults ≥65 years of age who had \nalready received a 2023- 2024 formula COVID -19 vaccine dose, 68.4% percent reported that \nthey definitely would get an additional dose of 2023-2024 formula COVID -19 vaccine if it is \nrecommended for them. The majority of work group members thought recommending an \nadditional dose of 2023- 2024 formula COVID -19 vaccine for older adults probably would be \nacceptable to key stakeholders . \nFor feasibility, Dr. Wallace reminded the committee that COVID -19 vaccines are currently on the \ncommercial market and an ACIP recommendation would be needed for insurance coverage of \nan additional dose. An additional dose recommendation would leverage existing infrastructure and vaccine product. However, it would add complexity to the current recommendations, which \ncould enhance vaccine and system fatigue. Access -related barriers to COVID -19 vaccines and \ndisparities in vaccine uptake remain. Additional dose recommendations may further heighten those inequities, but lack of recommendation limits access to those able to pay for vaccine out \nof pocket. The work group’s opinion was that an additional dose of the 20 23-2024 formula of \nvaccine probably would be feasible to implement among older adults. \nIn terms of the resource use domain, the full economic analysis presented by Dr. Proser \nshowed that an additional dose among adults ≥65 years of age had an ICER of about $ 250,000 \nper QALY . However, the ICERs became more favorable in scenarios that approximated the \nhigher risk, which may be seen with underlying medical conditions or advanced age. \n9 \n \n   \n \n     \n   \n    \n \n  \n     \n  \n  \n   \n     \n  \n  \n   \n   \n  \n     \n \n  \n   \n   \n \n \n \n  \n  \n     \n  \n    \n   \n \n   \n  \n \n \n \n  \n \n  \n \n \n \n   \n \n An additional dose of COVID -19 vaccine is likely more cost-effective in populations with a higher \nprevalence of risk factors, such as underlying conditions, which increase their probability of \nhospitalization due to COVID -19. When asked whether an additional dose of the 20 23-2024 \nformula COVID -19 vaccine in older adults is a reasonable and efficient allocation of resources , \nthe work group response was “probably yes.” \nTo summarize the work group interpretations , the greatest benefit of a vaccine dose would be in \nthose who have not yet received a 2023-2024 formula dose, particularly older adults and those \nwith underlying medical conditions. The data presented during this session emphasize the \nimportance of any dose of updated COVID -19 vaccine in older adults. Risk of severe illness due \nto COVID -19 continues throughout the year and is highest in those ≥ 65 years of age. Within \nadults ≥65 year of age, risk increases with increasing age. Receipt of the 2023-20 24 formula \nCOVID -19 vaccine provides protection against JN .1 and other circulating variants. However, VE \nis expected to wane. In the past, greater durability has been observed in the protection against \ncritical illness. A “may ” recommendation would provide flexibility for older adults to obtain an \nadditional dose if they or their HCP feel they would benefit. The most benefit would likely be in \nthose with underlying medical conditions, advanced age, or circumstances that may increase risk, such as being a nursing home resident. An additional dose in adults ≥65 years of age may \nrestore protection that has waned. However, this will be a smaller incremental benefit on top of \nthe protection that is still being provided by the initial 2023-2024 formula COVID -19 vaccine \ndose. The cost-effectiveness of an additional dose depends on COVID -19 hospitalization rates \nin the coming months and the patient risk factors for severe illness due to COVID -19. As \nCOVID -19 epidemiology changes with time, additional dose recommendations may not be \nneeded in the future. \nWhen considering an additional dose recommendation, the work group felt that a “may ” \nrecommendation would provide flexibility for those ≥65 years of age to get an additional dose if \nthey or their HCP feel they would benefit. For the overall balance of consequences, the work \ngroup was split between judgments that “the balance between desirable and undesirable \nconsequences is closely balanced or uncertain” and “desirable consequences probably \noutweigh undesirable consequences in most settings.” For type of recommendation, the majority \npolled to recommend the intervention for individuals based on shared clinical decision-making, \nwhich for COVID -19 vaccines has typically been referred to as a “may ” recommendation. The \nproposed ACIP language is as follows: \nACIP recommends that persons ≥65 years of age may receive an additional dose of the \n2023-2024 formula COVID -19 vaccine. \nThe proposed Clinical Considerations language is as follows: \nPeople ages 65 years and older may receive 1 additional dose of any updated (2023– 2024 Formula) COVID -19 vaccine (i.e., Moderna, Novavax, Pfizer -BioNTech), informed \nby the clinical judgement of a healthcare provider and personal preference and circumstances. Considerations for the additional dose may include a person’s risk for \nsevere COVID -19 due to age and the presence of underlying medical conditions. The \nadditional dose is administered at least 4 months following the previous dose of updated \n(2023– 2024 Formula) COVID -19 vaccine. \nDr. Loehr asked whether the work group considered recommending this for people ≥ 75 years of \nage, given that there seems to be a fairly dramatic change between 65 and 75. \n10 \n \n   \n  \n  \n      \n \n \n \n \n \n      \n      \n    \n       \n   \n  \n \n   \n \n \n  \n   \n   \n    \n   \n   \n    \n \n      \n \n \n \n     \n    \n   \n \n  \n \n   \n    \n    \n \n \n  Dr. Wallace indicated that the work group did have considerations of other age groups, including those ≥75 years of age. One of the key drivers that led to dropping it down to ≥65 years of age \nwas the equity concerns that people ≥75 years of age would likely cause inequities for those in \nminority groups that are still experiencing severe illness in persons 65─74 years of age. \nDr. Long said it seemed like it would be difficult to inform providers on what they ought to do with this recommendation as far as timing, and whether certain people should be given the booster now or wait to see what is occurring with the epidemiology and give it closer to when \nthey might be at more risk. \nDr. Loehr said he was wrestling with “ should” versus “may ” because he was thinking that there \nis a fair amount of benefit, and he tends to be more flexible. While “should” was appealing to \nhim at this point, he also could see many reasons why “may ” would makes sense, including \ncost-effectiveness and seasonality. In his personal opinion, he probably would give this again in \nFebruary or March for those people who are particularly high risk (e.g., those ≥75 years of age, \nimmunocompromised persons, those with high-risk conditions ). \nDr. Kotton said she had similar thoughts as Dr. Loehr. From her perspective as an active \nclinician in the field, many people she has spoken with did not even know that they should have \nhad an updated vaccine since September 2023. “May” seemed too soft to her, especially for the \nmost vulnerable populations. The American public is not aware of the fact that they actually \nshould be getting these vaccines. They should have already had the 2023-2024 updated \nvaccine, but the majority have not. From a public health perspective, she would be concerned if \nACIP did not make a clear-cut recommendation. She would advocate for clarity for “should” get \nthe updated vaccine, which was what ACIP said in September 2023, and people in the highest \nrisk groups “ should” get an additional dose. Furthermore, also advocated for clarity and \nsimplicity in terms of the issue of 4 months after the prior dose and 2 months for \nimmunocompromised after the last dose, which is confusing to clinicians. \nDr. Cineas voiced her agreement with Dr. Kotton about harmonizing “should” for both the first \nand second dose to make it easier for providers in counseling patients and to enhance uptake \namong those who may be getting their first updated vaccine. \nDr. Brooks noted that the work group discussed \"should\" versus \"may .\" In terms of the potential \ncons, beyond the science, it is still necessary to get the population vaccinated. There is now \nmore vaccine hesitancy , vaccine fatigue, and lack of confidence in a single dose. People under \n65 years of age will wonder why they do not get the vaccine. Allowing for the flexibility of \"may\" \nversus \"should\" may get more people vaccinated, including those <65 years of age, \nimmunocompromised, and those ≥65 years of age. \nDr. Loehr said that while he appreciated that perspective, most people com e in either wanting \nthe vaccine or not. They do have the data for people who have already gotten their 2023-2024 \nformula, 68% of whom would be happy to get a booster if they knew it was recommended. He \nwas thinking more about making it easier for providers to recommend this for everyone who walks in the door who fits the criteria. While he was not yet sure how he would vote, he did not think a “may” recommendation would get more people vaccinated. \n11 \n \n  \n   \n   \n \n  \n \n \n  \n  \n \n    \n \n \n  \n  \n \n  \n    \n  \n  \n  \n \n  \n    \n \n \n \n \n  \n  \n \n \n \n  \n \n \n     \n  \n \n \n \n \n  \n   \n    \n  \n Dr. Daley acknowledged that the work group considered a number of these options, and there \nwas some difference of opinion among work group members. In some ways , a \"may\" \nrecommendation was a reflection of some difference of opinion on the part of the work group. \nEveryone recognizes that communication is key and that how strongly a provider endorses this \nin their practice is really important. It is also important to recognize that vaccination is giving in \nmany settings now, such as pharmacies, where long conversations might not be possible. It \nmight be harder to communicate a \"may\" recommendation than a \"should\" recommendation, which might be a shorter conversation of, “You should get your vaccine today .” \nDr. Loehr moved that ACIP accept the language as presented, specifically saying \"may\" receive an additional dose. Dr. Brooks seconded the motion. \nDr. Kotton made a motion to strengthen the language to read \"should\" rather than \"may.\" Dr. \nLong seconded the motion. Dr. Daskalakis echoed what Dr. Daley said about \"may\" providing permissiveness for people \nwho are already very connected to and interested in vaccination. He also agreed with Dr. \nKotton’s comment that it is important to do better in terms of communicating the importance of \nthe initial dose. More absolute statements around vaccines sometimes will create a chilling \neffect for the folks who have not been vaccinated. In this scenario, it may be worth thinking \nabout the population of folks who have already been vaccinated, who are suggestible for a \nvaccine, and who will likely take this recommendation on the value of an additional dose as something that may be right for them . \nDr. Kotton said that as a clinician who provides a tremendous number of vaccines to adults, she has not necessarily found that to be true in her practice. When CDC says \"may,\" some people \ndo not think that means anything and does not mean someone needs to do it. “Should” is quite clear. She would like additional data to back up that in this scenario, the focus should be on those who are already vaccinated. \nDr. Long thought perhaps they were getting too hung up on “should” and asked whether “may” \ncould be deleted so that the statement simply read, “ACIP recommends that persons ≥65 years \nof age receive an additional dose of the 2023-2024 formula COVID -19 vaccine.” This way, the \nimplication would be “should.” \nDr. Wharton said she thought that would be acceptable language for an ACIP recommendation, \nalthough it was not how many other vaccine recommendations have been worded. However, \nthat would be an amendment. \nDr. Kotton requested clarity on the work group interpretation. The work group interpretation on \nSlide 77 states, “We recommend the intervention for individuals based on shared clinical \ndecision-making.” That was not actually the proposed voting language for the vote. She asked \nwhether they actually would be recommending the somewhat dreaded shared clinical decision-\nmaking, which makes vaccine implementation very challenging. \nDr. Wharton clarified that the “may” language as the COVID vaccine recommendations have \nbeen made over the last couple of years is a shared clinical decision-making recommendation. \nFor plain language purposes, it has been worded as proposed. From an implementation perspective, this is a shared clinical decision-making recommendation. \n12 \n \n  \n \n \n   \n \n \n  \n    \n  \n \n  \n     \n \n    \n  \n   \n \n   \n    \n  \n  \n \n  \n  \n  \n \n   \n   \n  \n   \n  \n  \n \n   \n   \n    \n    \n \n \n   \n    \n   \n    \n  \n \n \n  Dr. Loehr asked for clarity on whether they would first vote on the amended recommendation using the word “should” and then carry forward the final language to the afternoon voting \nsession. \nDr. Long requested more time to hear other opinions before voting on the amendment to the \nlanguage. Dr. Wharton clarified that the “should\" recommendation from the fall for everyone to receive a \nsingle updated dose still stands and would not be replaced by this vote in anyway. Everyone \nshould still get their updated 2023-2024 vaccine. \nDr. Chen said he was struck by the fact that, even though there is a waxing and waning of the \nburden of disease, it really did not completely disappear. It is probably lost, even on some \nclinicians, that there are significant hospitalizations and deaths even in the summer. The burden \nof disease, risks associate d with age, and other underlying conditions also motivated him to see \nthe importance of how the second booster dose could have a significant improvement in the \npopulation who receives it . Therefore, he favored the change to \"should.\" Having heard that this \nvote is applicable to a very small portion of the population, he was now stuck and was thinking \nthat the \"may\" language would be okay. However, he still wanted to make clear that vaccination \nis extremely important and whatever they can do to improve language overall to increase \nclinicians to be motivated to give a very strong recommendation to their patient population in \naddition to all patients understanding the importance of vaccination would be a goal. \nDr. Wharton clarified that they would be voting first on the amended language that would \nreplace \"may\" with \"should.\" If that amendment passed, the amended language would be taken \nforward for a vote in the afternoon following public comment. If the amendment fail ed, they \nwould return to the original motion that had the \"may\" language. \nDr. Fryhofer (AMA) said that speaking as a practicing physician and a member of the COVID Vaccine Work Group , she found the day’s discussion very helpful. There is still so much \npreventable disease, because COVID does not have a defined seasonality like influenza and \nthere are still many hospitalizations and deaths that could be prevented. She appreciated Dr. \nDaskalakis ’ comment about the people who are against vaccines and how a \"should\" \nrecommendation might affect them. However, a \"should\" recommendation does support vaccine \nconfidence and the belief that this vaccine will save lives, prevent hospitalizations, and prevent \ndeaths. She worries about shared clinical decision-making, or a \"may\" recommendation, \nbecause many people are getting vaccines in pharmacies. There is still confusion about what \npharmacies can and cannot administer, and they do not have the knowledge of a patient's \nmedical conditions and chronic illnesses like their personal physician or provider does. She was very impressed with Dr. Kotton’s and Dr. Long's comments, which changed the way she was \nthinking about this voting language. \nDr. Schmader (AGS) said that from a geriatrics perspective and within a society, talking with patients and geriatricians, there is a wide variety of opinions about this that land toward \"should\" \nbut at least \"may.\" \"May\" has to do with uncertainty about disease burden and effectiveness. \nThere is definitely a subset of people with vaccine fatigue and inertia. Some of the individuals in \nthis subset will go out right away and get the vaccine and others will not. A lot of people are thinking that there will be a vaccine in the fall, so they will just wait for that. \n13 \n \n     \n  \n \n    \n  \n  \n \n   \n    \n    \n    \n \n   \n  \n  \n     \n     \n  \n  \n   \n    \n \n  \n \n      \n \n \n \n     \n  \n \n \n \n \n \n \n \n   \n \n \n \n \n \n    \n  \n      \n \n    \n  Dr. Hopkins (NFID) said he thought this very important discussion would affect many people in \nthe population. While it is important to think about this additional dose, it needs to be coupled \nwith very strong language from ACIP and the liaisons to make sure that those who have not \nreceived a first dose of the 2023-2024 vaccine get that. Efforts must be made to better protect \nthose ≥ 65 years of age, and acknowledging Dr. Kotton's comments, the immun ocompromised \npopulation needs additional protection. \nDr. Rockwell (AAFP) said that speaking as a clinician and for private practice physicians, she \nthought the stronger language of \"should\" was better because it helped take out some of the \nambiguity about the \"may.\" In scholarly work and academics, they understand that. It also helps \nwith EHRs when there are best practice alerts. \nDr. Goldman (ACP) said that as a practicing internal medical physician, he thought jurisdictions \nhave different populations that can create some contention around vaccines. The \"may\" \nrecommendation can be more effective as far as explaining the need for vaccine and the \nflexibility to practicing physicians in different areas. While he does think this is an effective \nvaccine and there is still vaccine-preventable disease, with the issues of vaccine fatigue and the \ncontention that this particular vaccine has c reated over the years, having a \"should\" vaccination \nrecommendation may actually create other issues with getting the rest of patients vaccinated as \nnecessary for other recommended vaccines on the schedule. He suggested \"may\" because that \ncould at least give the flexibility for the practicing physician to be able to have the conversation \nwith the patient and separate it from issues of other vaccines they need to get as well . \nMs. Howell (AIM) noted that with long -term care residents being at high risk for severe \noutcomes due to COVID-19, she wondered whether with a \"may\" recommendation, there would \nstill be a requirement for LTCFs to offer COVID -19 vaccine to their residents or if it need to be a \n\"should\" recommendation for that to happen. \nDr. Wallace said she thought that LTCF could offer the vaccine to their residents under either \nrecommendation, and they certainly would fall into the high-risk category that would be \nparticularly important under a \"may\" recommendation. \nAs a reminder, Dr. Kotton made a motion to strengthen the language to read \"should\" rather \nthan \"may.\" Dr. Long seconded the motion. The motion passed with 12 affirmative votes and 1 abstention to take the following language forward for a vote: \nACIP recommends that persons ≥65 years of age should receive an additional dose of the 2023-2024 formula COVID -19 vaccine. \nAs a point of clarification, Dr. Kotton asked whether they would be voting on the \nimmunocompromised and the second dose. \nDr. Wharton said that they would not be voting on this but would ask the team how this might be \nhandled in the context of clinical considerations to make guidance clearer. \nDr. Lakshmi Panagiotakopoulos (CDC/NCIRD) presented the next steps for the COVID -19 \nvaccine program , beginning by discussing the question, “Can we improve the current COVID -19 \nvaccine policy timeline? ” In Fall 2023, the COVID -19 vaccine policy decision occurred as \nfollows. The mRNA updated 2023-2024 formula vaccines were authorized or approved on \nSeptember 11, 2023. The ACIP met September 12, 2023, to review the available evidence for \nthe updated COVID -19 vaccines. \n14 \n \n     \n     \n   \n  \n \n  \n    \n  \n   \n \n \n  \n \n \n  \n   \n \n \n   \n  \n   \n \n \n   \n \n  \n  \n  \n    \n  \n \n   \n \n    \n  \n     \n  \n \n \n \n \n  \n \n  \n \n \n During that meeting, ACIP recommended the updated COVID-19 vaccines as authorized under \nEUA or approved by BLA in persons ≥6 months of age. Moderna and Pfizer -BioNTech vaccines \nwere recommended for person ≥6 months of age and the Novavax COVID -19 vaccine, which \nwas authorized for use on October 3, 2023, was recommended in persons ≥12 years of age. Of \nnote, there was a general expectation that vaccines would be widely available immediately \nfollowing the recommendations. \nIn fall 2023, there was uncertainty around the recommendations prior to the meeting, which \nmade planning for state and local vaccine programs challenging. Vaccine orders had to be \nplaced prior to knowing the groups for whom the vaccine would be recommended. Stakeholder \npresentations, provider toolkits, and webpages all had to be updated after the recommendation was made, which limited the available window for communication of the recommendation prior to the respiratory virus season. There were also reports of issues with vaccine access, including \namong those at highest risk of severe illness. \nA revised timeframe for the 2024-2025 COVID -19 vaccine vote and recommendation during the \nJune meeting would allow for more lead time between when a recommendation is made to \nwhen vaccines are manufactured and distributed. The proposed plan for 2024 would include a \nJune ACIP meeting to review the evidence for updated COVID-19 vaccine recommendations, \nwhich would include World Health Organization ( WHO) and Food and Drug Administration \n(FDA ) antigen selections, manufacturer studies , immunogenicity data, cumulative effectiveness \nand safety data, epidemiology from current and prior years, uptake from current and prior years , \nand cost-effectiveness analyses . ACIP would then vote on the updated COVID-19 vaccine \nrecommendations in June. The 2024-2025 formula would become available as regulatory \nactions are taken by the FDA and vaccines are distributed by manufacturers. \nOne of the biggest benefits of a June COVID -19 vaccine policy decision is that it would enable \nearly planning across the entirety of the healthcare delivery system, including national, state, \nand local public health departments; large and small practices; and other venues for vaccine \ndelivery, such as pharmacies. Another benefit is that it would allow time for clear communication \nof recommendations. It also would provide vaccine sites with earlier information on which to \nbase vaccine ordering decisions. Vaccines potentially could become available immediately \nfollowing FDA authorization or approval. \nThere are over 4 years of data on COVID -19 and over 3 years of data on COVID -19 vaccines . \nThere is a well -established precedent from the influenza vaccine recommendations. The \ninfluenza virus also evolves rapidly and requires updates to vaccine antigens. It is unlikely there \nwill be more data between June and September that would influence the updated COVID -19 \nvaccine policy decision. The increased lead time would ease implementation challenges for \nvaccine providers, including earlier information on vaccine recommendations to inform ordering, \nwhich would allow providers to recommend the vaccine in anticipation of availability, train staff \nto counsel patients who are making appointments for influenza vaccine, and make informed \ndecisions. The increase lead time also would allow for clearer messaging in provider and patient \neducational materials. \nThis plan was presented to the COVID-19 ACIP Work Group. Work group members were in \nfavor of moving the decision to June and discussed many ways that this could ease \nimplementation challenges, including clearer communication of vaccine policy and increased \nlead time for clinicians. Work group members emphasized that communication surrounding a recommendation prior to vaccine availability, as done routinely for influenza vaccine, will be \nimportant. \n15 \n \n  \n  \n   \n  \n \n  \n  \n \n     \n  \n  \n \n \n   \n     \n  \n \n \n    \n      \n \n   \n   \n   \n   \n    \n \n \n  \n   \n \n     \n  \n    \n  \n \n \n \n    \n \n \n  \n   \n \n \n   \n   \n  \n   Dr. Chen asked whether there is an understanding of how the Bridge Access Program has had \nan effect on implementation and uptake and if there is an update on the move beyond the \nBridge Access Program and Vaccines for Adults . In addition, he asked whether there would be \nmore data on concomitant administration of COVID, influenza, and RSV vaccines . The lack of \ndata has been a barrier in trying to communicate confidence with these vaccines and trying to \naccomplish administration of all of them in a single visi t. \nDr. Chatham -Stephens responded that the Bridge Access Program has been tracking these \ndiscussions. As noted, additional lead time would help with any transition to an updated vaccine \nfor the next season. They are aware of this and are incorporating these discussions into their plans. \nDr. Wallace indicated that simultaneous administration is still part of general best practice. \nThere are no concerns with administering COVID vaccines with influenza, RSV, or other \nvaccines. This is always being monitored and new information is continuously being collected. \nDr. Long thought the June decision sounded appropriate in terms of marrying it to what doctor s \nanticipate now with influenza. However, it was unclear whether the vote in June would be to \nrecommend a universal dose for adults ≥ 65 years of age or for strain selection. \nDr. Wharton clarified that strain selection is done by FDA and the FDA’s advisory committee, VRBPAC, will be weighing in on that. T hat is not a decision that ACIP is asked to weigh in on. \nThe expectation is that in June, the work group will have a proposal for the committee on \nproposed use of COVID- 19 vaccines in the f all. Dr. Kaslow (FDA) confirmed that the strain \nselection decision would be made by FDA following the VRBPAC meeting, which is scheduled \nfor May 16, 2024. \nDr. Long observed that if the vote later in the afternoon was going to be for everyone ≥65 years \nof age or ≥70 years of age to get the vaccine now, it has been well over 4 months since \nSeptember or October when most people got the vaccine. It seems like it would impact the cost-\neffectiveness if 6 months later ACIP suggested that they all get it again. A window of 4 months \ndid not make sense when circulation is pretty low right now. For example, about 10% of \nspecimens in Philadelphia are positive for COVID -19 at this time. It was not clear why they \nwould make a very short -term recommendation when they would be considering a longer -term \nrecommendation in less than 4 months . \nDr. Wharton said that assuming that there is an updated vaccine for 2024-2025, that vaccine will \nnot be available until fall. That is a number of months away, even though ACIP will be \ndiscussing it in June. \nDr. Daley expressed appreciation for Dr. Long’s call for clarification and distinction between \nthose. Work group members raised the issue of what happens in June 2024 in terms of who \nshould get the vaccine. Influenza vaccination is thought of as seasonal, with vaccination \ncontinuing through March. The strategy for COVID is different. If someone wanted a vaccine in June and had not received a 2023-2024 vaccine, they would still be eligible and the vaccines \nwould not be expired. The likelihood of that happening given that they have had 9 months of \nopportunity probably continues to decrease but does not go down to zero. The vote planned for \nlater in the day was distinctly different because it would be for now and for a group that is at \nparticularly high risk by virtue of age. \n16 \n \n  \n  \n \n     \n  \n   \n   \n \n \n \n    \n \n  \n      \n     \n  \n  \n \n \n  \n  \n \n  \n \n \n \n \n   \n \n \n   \n \n \n     \n     \n \n \n   \n   \n  \n    \n  \n  A fresh decision will be made next year with an updated vaccine that is information by what is \nlearned over the past season about safety , effectiveness, barriers , and attitudes. If there is a \nbenefit now for people ≥65 years of age, he did not think ACIP should postpone that decision until June because it is a different decision for a different circumstance and different population. The work group was unanimous that there are many benefits to making a June decision, with \nthe recognition that there are some risks given unknown epidemiology, et cetera. He asked Dr. Kaslow whether, from the FDA perspective, ACIP ’s plan to make a recommendation for who \nshould receive a 2024-20 25 vaccine during the June ACIP meeting made sense. \nDr. Kaslow (FDA) confirmed that this does make sense. \nMs. Coyle (AIRA) acknowledged the role of health information technology systems (e.g., \nelectronic health record s, pharmacy system s, immunization information system s). Some of \nthese codes will have to be developed, and being able to get those out and updated in systems \ntakes time. Therefore, it is important to build in as much time as possible for that to ensure that \nas many systems as possible can make updates before vaccine administration and would be \ngreatly appreciated. That is, lengthening the lead time between licensure, recommendations , \nand vaccine administration would be helpful. \nVote: COVID-19 Vaccines \nAlthough public comment was presented prior to all of the votes during this meeting, the votes \nwere incorporated in summary with their respective sessions for the purpose of continuity. \nDr. Megan Wallace (CDC/NCIRD) read the following proposed ACIP voting language for \nCOVID -19 vaccines into the record: \nACIP recommends that persons ≥65 years of age should receive an additional dose of \nthe 2023-2024 formula COVID -19 vaccine. \nDr. Kaslow (FDA) made a few pre-vote comments noting that: 1) O nly 40% of people over 65 \nyears of age have received the indicated dose in the current package insert for the 2023-2024 formula. The biggest public health impact l ikely would come from increasing the number of \nindividuals ≥65 years of age getting that indicated dose; 2) There are suggestive data of longer \nduration, particularly against the outcomes that are most important, severe disease and death, \nin those who have had multiple exposures to the spike protein by infection or vaccines. In the \ncurrent context, individuals ≥65 years of age already have had multiple exposures to the spike \nprotein; 3) T here is a paucity of evidence for mRNA vaccines and protein -based vaccines given \nat this time in the ongoing pandemic. The context of receiving an additional dose now is quite \ndifferent than it was earlier in the pandemic. As presented, pre -existing immunity is quite robust \nand different than it was early in the pandemic; 4) If an antigen update is recommended this \nyear and is available in September, giving an additional dose of the current 2023-2024 \nformulation any later than June this year may not be optimal. Based on the current context and \nthe available data, this seems to be truly a “may ” recommendation supported by what is \nbasically Level 3 evidence. \n17 \n \n  \n \n \n   \n \n   \n \n   \n    \n \n    \n   \n         \n        \n \n \n \n \n   \n \n     \n  \n  \n    \n     \n \n \n \n \n   \n    \n    \n  \n    \n   \n \n \n \n  \n  \n      \n      \n   \n   \n  \n \n  \n \n  Motion/Vote: COVID -19 Vaccines \nDr. Kotton made a motion to approve the proposed recommendation stating, “ACIP \nrecommends that persons ≥65 years of age should receive an additional dose of the 2023-2024 \nformula COVID -19 vaccine.” Dr. Cineas seconded the motion. No COIs were declared. The \nmotion carried with 11 favoring, 1 opposing, and 1 abstaining. The disposition of the vote was \nas follows: \n11 Favored: Brooks, Beigel, Chen, Cineas, Clark, Daley, Grimes, Hance, Kotton, Loehr, Marshall \n1 Opposed: Long \n1 Abstained: Kaslow \nDiscussion Points \nMembers and Ex Officios were invited to make comments following the votes. \nReflecting on the COVID vaccination vote, Dr. Daley indicated that he personally would have felt \ncomfortable with a “should” or “may ” recommendation. While the ACIP voted for a “should” \nrecommendation, the points Dr. Kaslow raised do not go away and should be taken back to the \nwork group and discussed. The COVID Work Group had differences of opinion about where \nthey landed. This decision will arise for years to come, including in June. This is a reason to \npause and be humble. \nCHIKUNGUNYA VACCINE \nDr. Wilbur Chen, Chair of the ACIP Chikungunya Vaccines Work Group, introduced the \nchikungunya vaccines session. H e reminded the committee that the chikungunya vaccine \nmanufactured by Valneva was licensed in the US in November 2023. No other chikungunya \nvaccine is licensed globally, and there are no existing ACIP chikungunya vaccine \nrecommendations. The Chikungunya Vaccines Work Group is developing policy options for \nACIP ’s consideration for use of chikungunya vaccine among US persons at risk of chikungunya, \nincluding travelers, laboratory workers , and residents of US territories and states with risk of \ntransmission. \nDr. Susan Hills (CDC/NCEZID) reported that the FDA licensed the Valneva’s live attenuated \nchikungunya vaccine IXCHIQ® was approved on November 9, 2023. The vaccine was approved \nfor individuals at increased risk of exposure to c hikungunya virus as a single dose in individuals \n≥18 years of age. The vaccine is contraindicated for immunocompromised individuals and to \nindividuals with a history of a severe allergic reaction to any component of IXCHIQ®. Two \n“Warnings and Precautions ” are listed; first, the vaccine may cause severe or prolonged \nchikungunya-like adverse reactions, and second, vaccine viremia occurs in the first week \nfollowing vaccination and there are no data on the risk of vertical transmission. \n18 \n \n   \n   \n  \n \n    \n   \n   \n    \n  \n  \n     \n \n      \n     \n   \n   \n    \n  \n \n \n \n  \n    \n  \n    \n   \n   \n  \n    \n \n \n \n   \n   \n \n \n   \n     \n \n \n  \n \n \n \n \n \n  \n \n Dr. Hills told the committee that the vaccine was licensed through the accelerated approval \npathway. With accelerated approval, demonstration of effectiveness is based on control led \nclinical trials showing the vaccine has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefits. For the chikungunya vaccine, the marker of protection was based on a neutralizing antibody titer estimated from a validated non-human primate (NHP) model. With \nthis approval pathway, there is a post-licensure requirement for controlled trials to confirm the \nclinical benefits. The FDA has required 2 post-marketing studies. The first is a VE case -control \nstudy in adolescents and adults ≥12 years of age. This study will be conducted in Brazil and is \nplanned to start by March 2026 and be completed by March 2028. The second is a pragmatic \nrandomized control trial (RCT) for effectiveness and safety in adults in an endemic area, w hich \nis planned for initiation by October 2025 and completion by July 2029. \nDr. Hills (CDC/NCEZID) reminded the committee that c hikungunya virus is an alphavirus that is \ntransmitted primarily by Aedes species mosquitoes, primarily Aedes aegypti and Aedes \nalbopictus . Uncommon modes of chikungunya virus transmission include laboratory exposure, \nintrauterine and intrapartum transmission, and bloodborne transmission through needlestick \ninjury. Chikungunya virus occurs in tropical and subtropical regions and periodically causes \nlarge outbreaks throughout most parts of the world. Occasional transmission has occurred in \ntemperate areas. The virus periodically causes large outbreaks, with high attack rates among \none-third to three-quarters of the population affec ted. \nClinical illness is characterized by the acute onset of fever and joint pain, which is often severe and can be debilitating. Other symptoms may include headache, rash, myalgia, and/or anorexia. \nIn the absence of specific antiviral treatment, the approach to management typically involves \nrest, fluids , and use of analgesics and antipyretics. Deaths are rare and are reported mostly in \nolder adults, particularly those with comorbidities, and young infants infected perinatally or by \nmosquito bites . Acute symptoms of c hikungunya usually resolve in about 7 to 10 days, but \nsome patients have a continuation or relapse of their joint symptoms in the months after acute \nillness and experience other symptoms , such as fatigue. About 50% of people have ongoing \narthralgia of variable severity for up to 3 months after infection, and about 30% may have \nongoing arthralgia for up to 12 months after infection. \nChikungunya is a reportable disease in the US, with a pproximately 100 to 200 cases reported \nannually ; there is likely substantial underdiagnosis and underreporting. Infections are most \ncommonly acquired in Asia and the Americas , with specific locations of acquisition influenced by \nlocal transmission patterns which vary from year -to-year. In 2023, there was a large outbreak of \nchikungunya in Paraguay. Among all US travelers to destinations with risk of c hikungunya, \nfewer than 1% travel to Paraguay. Among all US traveler chikungunya cases reported in 2023, \n25% (20 of 80) were among persons who traveled to Paraguay. \nDr. Hills reviewed data on vaccine safety that had been reviewed by the work group.  Overall, \nthe work group summary of vaccine safety is that the live attenuated c hikungunya vaccine is a \nreactogenic vaccine. Because safety data have only been gathered in about 3,500 subjects, it \nwill be important to continue to monitor vaccine safety post-licensure as the vaccine is used in \nlarger populations. \nThe work group’s assessment was that c hikungunya is a disease that can result in severe \narthralgia during the acute illness, rare serious complications, and sometimes long-term \narthralgia. The highest risk for severe outcomes is among older adults, particularly those with \ncomorbidities, and neonates and young infants . \n19 \n \n   \n   \n   \n \n    \n \n  \n \n \n \n \n \n \n  \n \n  \n    \n \n \n \n    \n   \n  \n \n   \n \n \n  \n  \n     \n   \n \n    \n    \n  \n  \n \n  \n \n  \n  \n  \n \n \n  \n  There is moderate disease burden among US travelers , with 100-200 cases reported annually . \nThere is substantially higher risk for infection if travel occurs during an outbreak . The vaccine is \nimmunogenic , but it also is reactogenic . \nDr. Hills presented the following draft recommendations for ACIP's consideration: \nChikungunya vaccine is recommended for persons aged ≥18 years traveling to a country or \nterritory where there is a chikungunya outbreak. \nIn addition, chikungunya vaccine may be considered for the following persons traveling to a \ncountry or territory without an outbreak but with evidence of chikungunya virus transmission \namong humans within the last 5 years: \nPersons aged >65 years, particularly those with underlying medical conditions, who are \nlikely to have at least moderate exposure to mosquitoes OR \nPersons staying for a cumulative period of 6 months or more \nAn outbreak will be defined as occurring when CDC posts information on an outbreak on the \nCDC website. A notice will be posted as soon as CDC becomes aware of an outbreak. A similar \nprocess is used in relation to cholera and for the cholera vaccine recommendations , with \ninformation posted when cholera outbreaks occur. \nThe second part of the proposed recommendation is a shared clinical decision-making \nrecommendation for certain individuals traveling to an area with documented human cases . \nThere is more uncertainty in the risk -benefit assessment in these cases. However, there are \nlikely to be circumstances in which some individuals might reasonably choose vaccination or \nsome providers might wish to recommend it. In these circumstances, it is appropriate for there \nto be a conversation between the HCP and patient about the risks and benefits, including the \nlikelihood of exposure based on factors such as activities, time of year, and duration of travel ; \nthe disease and its potential severity ; the vaccine’ s efficacy ; and the possibility of vaccine-\nassociated adverse events. This approach also allows the traveler ’s personal perceptions and \ntolerance of risks to be taken into account. \nKey risk factors for severe c hikungunya disease include older age and underlying medical \nconditions (e.g., diabetes, cardiac disease, hypertension) and that key risk factors for chronic \narthralgia after chikungunya are older age and pre-existing joint problems. A key risk factor for \nchikungunya virus infection among travelers is the intensity of transmission. If there is \nequivalent transmission in different areas, the cumulative duration of exposure becomes important. Moderate exposure could include travelers who might have at least 2 weeks of \ncumulative exposure to mosquitoes in indoor or outdoor settings . This does not include travelers \nwho might have limited exposure to mosquitoes (e.g., those traveling for business and likely to \nbe mainly in mosquito-protected indoor settings ). \nDr. Hills noted that when the work group was developing the recommendation options for ACIP ’s consideration, they aimed to develop recommendations that balance the desirable and \nundesirable effects of vaccination based on consideration of all of the disease and vaccine \nfactors. The “recommended” component of the recommendations aims to target the travelers \nwith highest risk, where the benefits of receiving the vaccine almost certainly outweigh the risks. The “may be considered” recommendation aims to include groups with higher risk where the \nwork group did not think a specific  recommendation was justified because there is more uncertainty in the risk -benefit assessment, but for which some individuals might reasonably \nchoose vaccination, some providers might reasonably wish to recommend it, and a discussion \n20 \n \n  \n \n \n    \n  \n \n  \n \n    \n \n \n \n  \n    \n \n \n   \n    \n \n \n   \n   \n \n \n  \n   \n \n   \n \n   \n \n  \n    \n  \n   \n   \n   \n \n   \n  \n \n  and decision-making based on a conversation between the provider and patient would be valuable. \nDr. Kotton asked whether there were any thoughts about an upper age limit by which this \nvaccine no longer would be given. Her concern regarded safety among non-\nimmunocompromised people in their 70s and 80s. \nDr. Hills shared some data to help provide some context to this. Data for arthralgia by age group \ndo not show that frequency and maximum severity increase with age. While there are few data, frequency of any particular adverse event ( AE) is similar or lower in older age groups. \nDr. Daley made a motion to approve the draft recommendation language as presented, which Dr. Long seconded. \nDr. Kotton noted that while it did not necessarily have to be in the vote language, it should be \nnon-immunocompromised persons ≥18 years of age. Dr. Hills indicated that this is clearly \nindicated in the top right corner of the package insert and will be included in the MMWR . \nDr. Cineas asked whether there were any data b eyond 1 year in terms of how durable the \nvaccine is for people who might be traveling multiple times to endemic or areas where there is \nan outbreak . \nDr. Hills indicated that the work group reviewed data for 2 years and found that seroresponse \nrates are very high at 2 years. The manufacturer is planning to continue to monitor for at least 5 \nyears. \nDr. Hills indicated that the plan is to create a table to accompany the recommendations that \ndescribes the various risk factors for chikungunya and risk of chikungunya virus infection. The \nwork group preferred to leave the proposed recommendation language fairly straightforward, \nand provide the table to facilitate provider/patient discussions . \nDr. Hills next presented the proposed policy options for chikungunya vaccine use among \nlaboratory workers . At least 44 cases of chikungunya virus infection among laboratory workers \nhave been reported worldwide during the last 50 years. Of these, 43 cases were overt disease, \n1 was an asymptomatic infection, and there were no deaths. Among US laboratorians , 4 \ndisease cases have been reported in the 8-year period since chikungunya became a nationally \nnotifiable disease in the US in 2015. Documented routes of transmission of chikungunya virus in \nthe laboratory have been through the aerosol route and the percutaneous routes. Among cases \nof percutaneous transmission with more detailed information available, 2 researchers \nexperienced a needlestick injury while they were working with and injecting mice. For the third \ncase, a researcher experienced a forceps prick while dissecting mosquitoes infected with \nchikungunya virus. Although not documented, transmission through accidental mucosal \nexposure is also possible. \n21 \n \n   \n   \n  \n  \n \n   \n \n  \n  \n \n \n \n \n  \n \n \n \n  \n \n     \n \n \n  \n     \n    \n \n  \n \n   \n   \n  \n \n  \n  \n  \n \n  \n \n  \n \n   \n  \n \n   \n    \n  \n   \n \n Factors the work group considered regarding recommendations for laboratory workers were that \nvaccination is required for only limited number of staff who might be exposed to live \nchikungunya virus . Vaccination is not necessary for workers handling routine clinical samples \nwho should be consistently using standard practices for handling patient samples. Therefore, \nrecommendations are only for laboratorians undertaking research or very specific diagnostic \nwork using live virus (e.g., plaque reduction neutrali zation tests ). The work group surmised that \nthe benefits of vaccination outweigh risks for small group of laboratorians working with live virus, given potential for acquiring chikungunya virus infection which can result in severe \npolyarthralgia and possibly chronic arthralgia. The work group proposed the following draft \nrecommendation for ACIP consideration: \nChikungunya vaccination is recommended for laboratory workers with a potential for exposure to chikungunya virus. \nThe recommendations would be accompanied by clear information for implementation, including \nnoting that a local institutional biosafety committees should undertake a risk assessment of the \npotential for exposure to chikungunya virus for each laboratory worker working with the virus, considering the type of work to be performed and the biosafety level at which work will be \nconducted; vaccination is not necessary for workers handling routine clinical samples. \nDr. Loehr made a motion to accept the proposed recommendation as written. Dr. Cineas \nseconded the motion. \nDr. Hills presented clinical guidance for use of live attenuated chikungunya vaccine in pregnant \nand breastfeeding individuals.  The spectrum of illness of chikungunya in pregnant persons \nappears to be similar to that among non-pregnant persons . Adverse outcomes such as fetal \nloss, stillbirth, or preterm birth as a result of vertical transmission have been documented but \nare rare. However, infection commonly results in adverse neonatal outcomes if pregnant \nindividuals are infected around the time of deliver y. In these cases, intrapartum transmission \noccurs in about 30% to 50% of cases. When infection occurs following intrapartum transmission, \nsevere and sometimes fatal illness can result. Clinical presentation in the newborn is commonly \nwith encephalopathy , sepsis-like illness , cardiac, dermatologic , and hemorrhagic manifestations. \nIn the setting of neonatal infection, n eurocognitive outcomes are often poor, particularly if the \ninitial clinical presentation is with encephalopathy. Young infants infected by mosquito -borne \ntransmission are also at risk for severe disease, particularly during the first few months of life. \nClinical presentations in young infants are similar to presentations in infected neonates. This \nissue is important because of its relevance to possible protection of young infants by transplacental transfer of antibodies after maternal vaccination, although this is theoretical. \nThe data are insufficient to determine whether there are any safety risks in vaccination during \npregnancy , given that pregnancy was an exclusion criterion in the clinical trials and only 2 \npregnant persons were inadvertently vaccinated. Both of the 2 women were vaccinated during \nthe first trimester. One was a 36-year -old who experienced a spontaneous abortion 59 days \nafter vaccination at a gestational age of about 10 to 14 weeks. The other was a 23-year -old who \nhad anembryonic pregnancy noted 53 days after vaccination and experienced a spontaneous \nabortion at 55 days at about 8 weeks gestation. It is important to note that anembryonic \npregnancies generally result from a chromosomal problem at conception. An estimated 20% to \n25% of all pregnancies lead to pregnancy loss , with the highest rates in the first trimester and \nincreasing rates with increasing maternal age. \n22 \n \n     \n     \n  \n   \n    \n   \n  \n \n  \n     \n \n  \n  \n   \n   \n \n  \n \n \n    \n \n \n  \n \n \n \n  \n \n \n \n   \n \n  \n \n   \n \n   \n  \n \n \n       \n \n \n \n  Vaccine viremia occurs in the first week following administration of c hikungunya vaccine, and it \nis not known if the vaccine virus can be vertically transmitted and cause fetal or neonatal \nadverse reactions. Under “Use in Specific Populations,” the package insert notes that a decision \nto administer chikungunya vaccine during pregnancy should take into consideration the \nindividual's risk of wild -type chikungunya virus infection, gestational age, and risks to the fetus \nor neonate from vertical transmission of wild-type chikungunya virus. It notes that if neonates \nare born within 14 days of their mother receiving chikungunya vaccine, they should be closely \nmonitored after birth for potential disease due to vaccine virus. \nIn the future, the work group will be considering recommendations for persons in US territories \nand states with risk of chikungunya virus transmission. Therefore, the vaccine potentially could \nbe used in a larger population of pregnant individuals in future than is anticipated with its use \namong travelers and laboratory workers in the near -term. Having considered the issues around \nrisks of chikungunya disease for pregnant individuals and their infants and vaccine use in \npregnancy, the objectives of chikungunya vaccination during pregnancy are to protect the \npregnant person from chikungunya virus infection and avoid maternal infection around the time \nof delivery to prevent intrapartum virus transmission and severe disease in the newborn. In \naddition, transplacental transfer of antibodies might also protect young infants from mosquito-\nborne transmission and severe disease. \nThe following is the work group’s proposed clinical guidance language for use of chikungunya \nvaccine in pregnant individuals : \nPregnant individuals should avoid the risk for chikungunya virus infection, if possible (e.g., \nby avoiding travel to an area with virus transmission, particularly during an outbreak). \nPregnancy is a precaution for vaccination with a live attenuated chikungunya vaccine. In \ngeneral, vaccination should be deferred until after delivery. However, when the risk of infection is high and exposure cannot be avoided, a healthcare provider should discuss with \na pregnant person the potential risks of chikungunya virus infection and the potential \nbenefits and risks of vaccination so that vaccination can be considered. \nIf pregnant persons choose to be vaccinated, out of caution vaccination should genuinely be avoided during the 1\nst trimester (until 14 weeks) gestation and after the 36th week of \ngestation. \n− Avoiding vaccination during the first trimester is preferred for two reasons. Firstly, pregnancy loss has been reported in two individuals vaccinated during the first \ntrimester, although one was an anembryonic pregnancy. In addition, the vaccine is \nreactogenic and can cause fever , and fever has been linked to birth defects in the 1\nst \ntrimester. \n− Avoidance of vaccination after the 36th week of gestation is to limit the risk of vaccine-\ninduced viremia occurring in the intrapartum period, and thus to reduce the theoretical risk for perinatal transmission and potential adverse outcomes.* \n*Vaccine viremia is considered to occur in most individuals in the first few days after vaccination and to decrease thereafte r; \nviremia was no longer detectable in any clinical trial subjects at 14 days after vaccination. \nIn line with common practice following vaccination with live vaccines, non-pregnant vaccine recipients should generally wait 4 weeks before becoming pregnant. If a pregnant person is inadvertently vaccinated outside of the preferred period or becomes pregnant within 4 \n23 \n \n   \n \n \n  \n  \n \n  \n  \n \n      \n   \n   \n   \n \n \n  \n \n \n \n    \n \n \n \n  \n \n  \n \n \n \n  \n \n \n \n \n  \n    \n   \n  \n  \n  \n   \n \n \n  \n weeks after the chikungunya vaccination, this should not be considered a reason to \nterminate the pregnancy. \nThis guidance is intended to maximize the benefits of vaccination while minimizing risks associated with vaccination during pregnancy. \nChikungunya viral ribonucleic acid ( RNA ) has been detected in breast milk of women in \nendemic areas on very rare occasions. No studies have reported detection of replicating virus. \nAlthough the data are limited, chikungunya virus transmission through breastfeeding has not \nbeen reported. No human data are available on whether chikungunya vaccine virus or \nantibodies are present in breast milk after vaccination. It is known in general that neonates and other infants less than 1 year of age are at risk for severe disease, particularly in the first few \nmonths of life, if infected with wild-type chikungunya virus. The vaccine virus is attenuated, but \nthere are no data on potential outcomes for an infant if c hikungunya vaccine virus was \ntransmitted by breastfeeding. \nIn the package insert for the vaccine, breastfeeding is neither a contraindication nor precaution \nfor vaccination. The language in the package insert notes that the developmental and health \nbenefits of breastfeeding should be considered, along with the mother ’s clinical need for the \nvaccine and any potential adverse effects on the breastfed child from the vaccine or from the \nmother’ s susceptibility to c hikungunya. The package insert also notes that vaccine viremia \noccurs after vaccination, but that any potential for transmission of the vaccine virus from mother \nto infant through breast milk is unknown. \nThe following is the work group’s proposed clinical guidance language for use of chikungunya \nvaccine in breastfeeding individuals: \nBreastfeeding individuals and their infants should avoid the risk for chikungunya virus \ninfection, if possible (e.g., by avoiding travel to an area with transmission particularly during \nan outbreak). \nIn the absence of data, breastfeeding is a precaution for vaccination. When the risk of \ninfection is high (e.g., during an outbreak) and exposure cannot be avoided, a health care provider should discuss with a breastfeeding individual the developmental and health \nbenefits of breastfeeding for the infant, the risks of chikungunya virus infection, and the \npotential benefits and risks of vaccination, and offer the vaccine to the breastfeeding person. \nAt the current time, the data are insufficient to make a recommendation to defer breastfeeding for any period after vaccination. \nDr. Riley , liaison representative from the American College of Obstetricians and Gynecologists \n(ACOG), expressed ACOG’s support for the use of the c hikungunya vaccine in pregnancy as a \nprecaution when infection risk is high and exposure cannot be avoided using shared clinical \ndecision-making. When chikungunya infection occurs around the time of delivery, it frequently \nresults in antepartum transmission t hat in and of itself results in severe outcomes for neonates. \nVaccination during pregnancy, particularly around the time of delivery or ≤36 weeks  gestation, \ncould protect the mother and the fetus. It is also possible that transplacental transfer of \nantibodies occurs and could protect young infants from mosquito-borne transmission. With the \nobserved severe outcomes when a pregnant individual gets infected around the time of delivery, any opportunity to protect a pregnant person before the antepartum period is beneficial. \n24 \n \n   \n   \n  \n  \n  \n \n  \n  \n  \n \n     \n   \n      \n   \n \n \n    \n \n \n   \n  \n \n  \n \n \n  \n \n \n \n \n  \n  While some live attenuated vaccines are contraindicated during pregnancy, other vaccines such \nas dengue, Ebola, and yellow fever have been licensed with pregnancy as a precaution. \nTherefore, in an outbreak situation or other time when infection risk is quite high, ACOG \nsupports the use of this vaccine during pregnancy to prevent the chances of a pregnant person acquiring the infection around the time of delivery. \nDr. Long said she was struck that there are no data on giving this vaccine to pregnant women, but they do not want to disenfranchise them from being immunized. She recalled the two \ninadvertently administered vaccines in the first trimester, both of which had adverse outcomes. \nDr. Dana Meaney -Delman, CDC, indicated that one was an anembryonic pregnancy that likely \nwas chromosomal in nature and unlikely biologically plausible to be related to the vaccine. While \nthey may never know more about those two pregnancies, the pregnancy losses occurred more \nthan 50 days out from vaccination, which also makes it unlikely. \nAlthough public comment was presented prior to the votes during this meeting, the votes were \nincorporated in this summary with their respective sessions for the purpose of continuity. \nVote #1: Chikungunya Vaccines for Travelers\nDr. Susan Hills (CDC/NCEZID) read the following proposed ACIP voting language into the \nrecord for c hikungunya vaccines pertaining to travelers: \nChikungunya vaccine is recommended for persons aged ≥18 years traveling to a country \nor territory where there is a chikungunya outbreak. \nIn addition, chikungunya vaccine may be considered for the following persons traveling \nto a country or territory without an outbreak but with evidence of chikungunya virus \ntransmission among humans within the last 5 years: \n─ Persons aged >65 years, particularly those with underlying medical conditions, who are likely to have at least moderate exposure to mosquitoes, OR \n─ Persons staying for a cumulative period of 6 months or more. \n25 \nMotion/Vote #1: Chikungunya Vaccines for Travelers \n \n  \n    \n \n \n  \n  \n \n \n \n \n     \n \n \n       \n   \n        \n        \n \n \n \n \n \n  \n \n \n \n \n \n    \n \n  \n  \n  \n    \n \n \n       \n   \n        \n       \n \n \n   \n  \n  \n  \n  Dr. Daley made a motion to approve the proposed Vote #1 recommendation for chikungunya \nvaccines stating, “ Chikungunya vaccine is recommended for persons aged ≥18 years traveling \nto a country or territory where there is a chikungunya outbreak. In addition, chikungunya vaccine \nmay be considered for the following persons traveling to a country or territory without an outbreak but with evidence of chikungunya virus transmission among humans within the last 5 \nyears: Persons aged >65 years, particularly those with underlying medical conditions, who are \nlikely to have at least moderate exposure to mosquitoes, OR Persons staying for a cumulative period of 6 months or more.” Dr. Long seconded the motion. No COIs were declared. The \nmotion carried with 12 favoring, 0 opposing, and 1 abstaining. The disposition of the vote was \nas follows: \n12 Favored: Brooks, Beigel, Chen, Cineas, Clark, Daley, Grimes, Hance, Kotton, Loehr, \nLong, Marshall \n0 Opposed: N/A \n1 Abstained: Kaslow \nVote #2: Chikungunya Vaccines for Laboratory Workers\nDr. Hills read the following proposed ACIP voting language into the record for chikungunya vaccines pertaining to laboratory workers: \nChikungunya vaccination is recommended for laboratory workers with potential for \nexposure to chikungunya virus. \nMotion/Vote #2: Chikungunya Vaccines for Travelers \nDr. Loehr made a motion to approve the proposed Vote #2 recommendation for chikungunya \nvaccines stating, “Chikungunya vaccination is recommended for laboratory workers with \npotential for exposure to chikungunya virus.” Dr. Cineas seconded the motion. No COIs were \ndeclared. The motion carried with 13 favoring, 0 opposing, and 0 abstaining. The disposition of \nthe vote was as follows: \n13 Favored: Brooks, Beigel, Chen, Cineas, Clark, Daley, Grimes, Hance, Kaslow, Kotton, \nLoehr, Long, Marshall \n0 Opposed: N/A \n0 Abstained: N/A \nMembers and Ex Officios were invited to make comments following the votes. Dr. Chen noted \nthat while the chikungunya vaccine was first licensed in the US, the burden of disease is global. \nHe expressed his hope that the discussions they had throughout the day would not negatively affect the consequences of implementation of the vaccine globally. He would like to continue to \nsee additional vaccines for other mosquito-borne agents in the US and around the world. \n26 \n \n    \n \n      \n   \n   \n  \n  \n   \n   \n \n \n   \n    \n  \n  \n  \n \n  \n  \n \n \n \n \n \n  \n \n   \n      \n   \n  \n  \n  \n    \n  \n     \n \n   \n \n    \n   \n  \n \n  \n \n  \n \n DIPHTHERIA AND TETANUS TOXOID (DT) VACCINE \nDr. Michele Hughes (CDC/NCIRD) provided an update on CDC’ s guidance for Td vaccines for \nyoung children. As part of the routine vaccination schedule, CDC recommends a primary series \nof the pediatric diphtheria-, tetanus -, and pertussis -containing vaccines (DTaP ) vaccines for \nchildren <7 years of age. For children<7 years of age who developed a contraindication to \npertussis -containing vaccines, CDC previously recommended the pediatric diphtheria and \ntetanus toxoid vaccine (DT) instead of DTaP. Recently, the s ole DT vaccine manufacturer in the \nUS discontinued DT production. The last available lot expired in April 2023. There is no longer \nDT vaccine available in the US. \nThe only contraindication specific to the pertussis component in DTa P is encephalopathy within \n7 days of vaccination that is not attributed to another cause. While the exact numbers are not \nknown, the occurrence of this AE is extremely rare. In light of DT no longer being an available \noption, CDC issued the following updated vaccination guidance for the use of Td in young \nchildren with a contraindication to pertussis -containing vaccines : \nCDC recommends young children receive DTaP as the first dose in the diphtheria, tetanus, \nand pertussis childhood vaccination series. \nCDC recommends continued use of DTaP unless a contraindication to pertussis -containing \nvaccines develops. \nFor young children who develop a contraindication to pertussis -containing vaccines, vaccine \nproviders may administer Td for all recommended remaining doses in place of DTaP. \nThe impact on diphtheria protection is uncertain. Td is a tetanus - and diphtheria toxoid-only \nformulation licensed only for ages ≥7 and older . The use of Td in this situation would be an off-\nlabel use. Td contains a lower dose of diphtheria toxoid compared to DT and the impact of this \nlower dose on the protection provided against diphtheria in young children is uncertain. There \nare no available data evaluating the effectiveness of Td against diphtheria when used as part of \nthe primary series in young childr en.  Children may have less protection against diphtheria and \nno additional protection against pertussis if they receive Td instead of DTaP. CDC has posted \nthis guidance on its website at www.cdc.gov/vaccines/vpd/dtap-tdap-td/hcp/td-offlabel.html . In \norder to be covered by VFC for children < 7 years of age, a minor update is needed. \nDr. Jeanne Santoli (CDC/NCIRD) gave an update on the current Td supply and the proposed \nVFC updates. As noted, MassBiologics has discontinued production of their Td vaccine, \nTdVax ™. Grifols, who is the exclusive distributor for TdVax ™, expects to have product available \nthrough approximately June 2024. Sanofi, who manufacturers Tenivac®, the only other US-\nlicensed Td vaccine, is taking steps to augment their available supply of Td for the US. \nHowever, it is anticipated that the supply of Td vaccine in the US market will be constrained during 2024. Temporary ordering controls have been put into place in the public and private sectors to help manage the gap in supply. Adult formulation tetanus and diphtheria toxoids and \nacellular pertussis vaccine ( Tdap) is available from both US -licensed manufacturers without \nsupply constraints at this time. Based on the rarity of developing a contraindication to pertussis -\ncontaining vaccines, the temporarily constrained supply of Td vaccine is not anticipated to prevent providers from utilizing Td vaccine for these children in the VFC program. \n27 \n \n    \n  \n  \n \n \n \n \n \n \n \n \n \n     \n    \n   \n \n  \n      \n \n  \n \n \n  \n \n  \n \n  \n \n \n \n \n \n \n  \n \n  \n \n       \n   \n        \n       \n        \n \n \n \n  Dr. Santoli indicated that the purpose of this resolution was to: 1) add Td vaccine for use in \nchildren <7 years of age for whom receipt of the pertussis component is contraindicated; and 2) \nupdate the language regarding the Tdap booster to align with ACIP recommendations. Eligible \ngroups include c hildren and adolescents aged 6 weeks through 18 years , which was \nunchanged. \nBecause Td is not currently included in the VFC program, the proposed language to add it to the \nVFC resolution is as follows: \nApprove the Vaccines for Children (VFC) resolution for diphtheria, tetanus, and pertussis \nvaccines. \nDr. Long noted that with anticipation that Td is frequently not stocked in places like emergency \ndepartments anymore, there already is language in the R ed Book stating that Tdap can be used \nif there is no Td. \nDr. Santoli indicated that in terms of the VFC Resolution, Tdap is absolutely covered for persons >7 years of age. It is not covered for the persons <7 years of age. \nIn terms of the recommendation, Dr. Hughes added that ACIP's previous recommendation that \nTdap can be used in lieu of Td would remain. \nDr. Long made a motion to accept the proposed wording for a vote, which Dr. Kotton seconded. \nVote: VFC Resolution for Diphtheria, Tetanus, and Pertussis Vaccines\nWhile public comment was presented prior to the votes, the votes were combined in this summary with their respective sessions for the purpose of continuity. \nApprove the Vaccines for Children (VFC) Resolution for diphtheria, tetanus, and \npertussis vaccines. \nMotion/Vote: VFC Resolution for Diphtheria, Tetanus, and Pertussis Vaccines \nDr. Long made a motion to approve the proposed recommendation for the VFC Resolution stating, “Approve the Vaccines for Children (VFC) Resolution for diphtheria, tetanus, and \npertussis vaccines.” Dr. Kotton seconded the motion. Dr. Chen declared a COI due to his active collaboration with MassBiologics, the maker of a DT vaccine. The motion carried with 12 favoring, 0 opposing, 0 abstaining, and 1 recusing. The disposition of the vote was as follows: \n12 Favored: Brooks, Beigel, Cineas, Clark, Daley, Grimes, Hance, Kaslow, Kotton, Loehr, \nLong, Marshall \n0 Opposed: N/A \n0 Abstained: N/A \n1 Recused: Chen \n28 \n \n  \n \n \n  \n \n   \n \n   \n \n \n  \n   \n    \n  \n  \n  \n \n   \n  \n \n \n    \n  \n    \n   \n \n  \n   \n \n \n   \n  \n    \n     \n \n   \n  \n   \n \n \n   \n       \n  \n     \n      \n \n \n  INFLUENZA VACCINES \nThe influenza session was opened by Dr. Jamie Loehr , ACIP Influenza Vaccine Work Group \nChair. \nDr. Aaron Frutos (CDC/NCIRD/ID) presented CDC’s interim estimates of 2023/2024 seasonal \ninfluenza VE. This year, 4 networks contributed to the interim estimates of VE against \nlaboratory -confirmed influenza for children, adolescents , and adults in the out-patient and in-\npatient settings.  \nThe methods used by each network to estimate influenza VE are very similar. All enrollees \nacross all networks sought medical care for acute respiratory illness (ARI). Patients are included \nfrom fall 2023 to early 2024. Each network uses a test-negative design, which compares the \nvaccination odds among case patients with influenza confirmed by molecular assay versus \ncontrol patients testing negative for influenza and SARS -CoV-2. Vaccination status was \ndetermined as the receipt of any of the 2023-2024 seasonal influenza vaccines according to medical records, immunization registries, claims data, and/or self-report. VE estimates were calculated for influenza A subtypes A (H1N1 )pdm09 and A (H3N2 ) when possible. VE was not \nestimated for some age groups and settings when the sample size was small or when models \ndid not converge. \nPediatric VE against any influenza ranged from 59% to 67% in out-patient settings and 52% to \n61% in the in-patient setting. VE estimates were consistent across networks. Pediatric VE \nagainst influenza A ranged from 46% to 59% in out-patient settings and 46% to 56% in the in-\npatient setting. Pediatric VE against influenza A (H1N1 )pdm09 ranged from 54% to 61% in out-\npatient settings and was 60% in the in-patient setting. Pediatric VE against influenza A(H3N2 ) \nwas 55% in out-patient settings and was not estimated in the in-patient setting. Pediatric V E \nagainst influenza B ranged from 64% to 89% in out-patient settings and was not estimated in \nthe in-patient setting. \nFor adults ≥18 years and older , vaccination prevalence ranged from 39% to 52% among test-\nnegative controls across settings. Adult VE against any influenza ranged from 33% to 49% in \nthe out-patient settings and 41% to 44% in the in- patient setting. Adult VE against influenza A \nranged from 27% to 46% in out-patient settings and 40% to 42% in the in-patient setting. Adult \nVE against influenza A( H1N1 )pdm09 was 25% in out-patient settings and 50% in the in-patient \nsetting. Adult VE against influenza A( H3N2 ) was 54% in the out-patient setting and was not \nestimated in the in-patient setting. Adult VE against influenza B was 78% in out-patient settings \nin 2 networks and 60% in the in-patient setting. Again, consistent results were observed across \nnetworks. Among adults ≥65 years of age, the prevalence of vaccination among test-negative controls \nranged from 48% to 68% across settings. VE against any influenza ranged from 41% to 51% in \nout-patient settings and was 42% in 2 networks in the in-patient setting. Among adults ≥65 \nyears of age, VE against influenza A ranged from 40% to 52% in out-patient settings and 42% \nto 47% in the in-patient setting. VE against influenza B for adults ≥65 years of age was 69% in \nout-patient settings and was not estimated in the in-patient setting. \n29 \n \n     \n  \n  \n \n  \n    \n  \n \n   \n   \n \n   \n    \n \n   \n \n \n   \n   \n   \n \n \n    \n     \n  \n     \n  \n  \n     \n  \n \n \n   \n  \n \n  \n  \n  \n  \n   \n  \n    \n \n \n  \n    \n    \n   \n  \n These estimates showed that vaccination with the 2023-2024 influenza vaccine reduced the risk \nfor medically -attended influenza out -patient visits and hospitalizations among children, \nadolescents, and adults across 22 US states. Vaccination was effective against both influenza \nA, mostly subtype A(H1N1)pdm09, and B Victoria viruses that have circulated this season. \nDr. Sophie Zhu (California Department of Public Health and CDC/PHIC/DWD) presented i nterim \ninfluenza VE a gainst laboratory -confirmed influenza in California for October 2023—January \n2024. New public health data reporting requirements in California offer an opportunity to \ncalculate VE against laboratory -confirmed influenza, resulting in estimates that are available \nahead of traditional platforms. As of January 1, 2023, all influenza vaccination records became \nreportable to the California Immunization Registry (CAIR). P ositive influenza results have been \nreportable in California since October 2019. Negative influenza results became reportable a s of \nJune 15, 2023 to the California Reportable Disease Information Exchange (CalREDIE ), the \nstate electronic communicable disease reporting system .  \nFor this analysis, influenza laboratory results were matched to immunization registry data to \ncalculate early VE estimates against laboratory -confirmed influenza in California during the \n2023-2024 influenza season. The estimates from this analysis reflect VE against l aboratory -\nconfirmed influenza using nucleic acid amplification tests and include persons tested for \ninfluenza from diverse care settings and symptom severity levels. VE is calculated using a case-\ncontrol design in which persons testing positive for influenza are case patients and persons \ntesting negative for influenza are control patients. \nPersons included in the analysis were all California residents ≥6 months of age with molecular \ntests for influenza A or B captured by the s tate electronic laboratory reporting system. Most \ninfluenza testing performed at clinical and commercial laboratories that report influenza A and B \ntest results do not perform subtyping. The dates of this analysis were October 1, 2023, through \nJanuary 31, 2024. Participants were considered vaccinated if there was at least 1 dose of \nseasonal influenza vaccine documented i n CAIR ≥ 14 days before testing. Adjusted VE was \ncalculated as VE = (1 – adjusted odds ratio) x 100% . A m ixed-effects logistic regression model \nwas used that was adjusted for age, ethnicity, testing week (random effect), and county (random \neffect). \nIn California, overall influenza virus positivity the week of February 19, 2024, was 6.5% and had \ndeclined from prior weeks. Based on subtyping at public health laboratories in California, this is \na predominantly H1 season so far. Of the samples, 82% have been influenza A and 75% have \nbeen H1. A total of 678,422 individuals were included in this analysis. This included 77,501 \ninfluenza-positive cases , which is about 11% positivity , and 600,921 influenza-negative control \npatients. The median age was 31 years for case patients and 44 years for control patients. \nThere was a similar breakdown of race and ethnicity for the case and control patients. Overall, \n28% of individuals were vaccinated and 18% of case patients were vaccinated overall versus \n29% of controls. Vaccination increased month-by -month from 13% during October to 34% \nduring April. A similar lower vaccination rate was seen in case versus control patients \nthroughout all time periods. \nAdjusted VE against laboratory -confirmed influenza overall was 45%. VE declined with \nincreasing age and was highest at 56% in children ≤ 18 years of age, 48% in adults 18─ 49 years \nof age, 36% in adults 50 ─64 years of age, and lowest at 30% in adults ≥65 years of age. VE \nagainst influenza A was lower than overall influenza VE, but was still protective at 42%. Over \n90% of cases in this analysis were influenza A, which is consistent with both California and \nnational trends. \n30 \n \n     \n    \n      \n   \n  \n \n  \n  \n \n  \n   \n \n \n   \n   \n    \n  \n    \n    \n   \n     \n   \n \n  \n    \n   \n  \n \n \n   \n  \n \n    \n     \n  \n  \n    \n     \n    \n  \n    \n  \n \n \n   \n  \n   \n \n    \n  \n    Age-specific VE declined with increasing age and was lowest for adults ≥65 years of age at \n29%. VE for influenza B was high at 76% . Estimates were generally comparable across younger \nage groups, ranging from 75% to 79% for persons 6 months ─49 years of age. Similar to \ninfluenza A, estimates were lower among adults ≥50 years of age. Less than 10% of cases were \ninfluenza B. \nMandatory public health data can be leveraged to calculate timely in-season influenza VE as an \nadditional estimate supporting existing public health influenza prevention efforts. Earlier \nestimates can inform public health action and messaging for additional prevention measures \nprior to the peak of influenza infections and could be especially informative for healthcare \nsettings that may need to reallocate resources to prepare for increased hospital capacity. \nC. Buddy Creech, MD, MPH (Vanderbilt University Medical Center) presented on the safety of \nquadrivalent live attenuated influenza vaccine ( LAIV4) in children with asthma. In this study, 151 \nchildren and adolescents 5–17 years of age with persistent asthma were randomized to LAIV (n \n= 79) or quadrivalent inactivated influenza vaccine ( IIV4) (n = 72). The primary objective was to \ncompare the proportion of participants who experienced asthma exacerbation during the 6 \nweeks after LAIV4 versus IIV4. Persistent asthma was defined as provider diagnosis of asthma \nplus prescription of a long-acting controller medication and an asthma exacerbation was defined \nas an acute episode of progressively worsening shortness of breath, cough, wheezing, chest \ntightness , or respiratory distress for which the patient sought medical attention or received a \nnew prescription for systemic corticosteroids. \nLAIV4 was not associated with increased asthma symptoms or asthma exacerbations in the 14-or 42-day windows following immunization. Rates of reactogenicity were similar between the 2 \ngroups, although myalgia and sore throat were more common in the IIV 4 arm. LAIV4 may be a \nsuitable option for children ≥5 years of age who have asthma, including those with moderate to \nsevere asthma. \nDr. Lisa Grohskopf (CDC/NCIRD/ID) provided an update on influenza B/Yamagata surveillance. \nUp until the late 1970s, the number of viruses in influenza vaccines varied from year -to-year. \nThere was variability in the formulation from year -to-year, starting around the 1978-1979 \nseason. C onsistent seasonal vaccination has been available with trivalent vaccines with an \nA/H1 , A/H3, and 1 B virus. During the 1980s, there was an appreciation that there were 2 \nlineages of influenza B viruses for which research evidence suggested that there was not \noptimal cross -immunity. There was only one B lineage in the vaccine, so one of the two had to \nbe selected for inclusion in the vaccine. Q uadrivalent influenza vaccines became available in \nthe market in 2013-2014 and c ontained 2 B viruses, 1 from each lineage. After the 2013-2014 \nseason, there was a gradual phase-in of the quadrivalent influenza vaccines . Some \nmanufacturers went from one season to the next from trivalent to quadrivalent. Some phased \nthem in within their brand over time. The transitioned to quadrivalent influenza vaccines was \nlargely complete before the 2021-2022 season, with only 1 lot of trivalent released that season. \nThere have now been a couple of seasons with only quadrivalent vaccines. \nAs Dr. Kondor presented during the October 2023 meeting, there have been no confirmed \nnaturally occurring influenza B/Yamagata viruses in global surveillance since March 2020. The \nLAIV contains B/Yamagata, so it is conceivable that this might be seen in surveillance. \nHowever, there have been no wild-type detections of naturally occurring B/Yamagata viruses . \nDuring the Fall 2023 discussions for Southern Hemisphere influenza vaccine composition, WHO \nand FDA concluded that coverage of influenza B/Yamagata was no longer warranted and \nshould be removed from vaccines as soon as feasible. \n31 \n \n   \n   \n  \n   \n  \n \n  \n  \n     \n     \n \n  \n   \n \n \n \n   \n  \n \n    \n    \n  \n   \n    \n  \n   \n   \n  \n    \n \n \n   \n \n  \n  \n \n  \n    \n     \n \n   \n \n  \n      \n \n  \n  \n \n \n  Since then, WHO met and made recommendations for the N orthern Hemisphere for the 2024-\n2025 season that include a second B virus for those countries that elect to use/ market a \nquadrivalent vaccine. Decisions regarding the composition are made by individual national \nregulatory authorities. For the US, that is the FDA. The FDA is set to discuss composition of \n2024-2025 US influenza vaccines on March 5, 2024. \nMs. Rebecca Coyle (AIRA) pointed out that the codes for trivalent vaccine have been \ninactivated because they have not been used in the last several seasons. For any upcoming \ndecisions, particularly by manufacturers that will be moving to trivalent influenza vaccine as \nsoon as this year, it will be to be important to have conversations as soon as possible about \nreactivating the old codes versus trying to create new codes. There is a relatively short period of \ntime between now and the next influenza season, so the time is now to make sure the codes are correct for billing to make this as seamless as possible. \nPOLIO VACCINE \nDr. Oliver Brooks, chair of the ACIP Polio Vaccine Work Group, introduced the polio vaccine \nsession. \nDr. Sarah Kidd (CDC/NCIRD) reminded the committee that paralytic disease occurs in < 1% of \npoliovirus infections and approximately 75% of infections are asymptomatic. There are 3 \npoliovirus serotypes with different epidemiological and clinical characteristics and immunity to \none serotype does not result in significant immunity to other serotypes. The ratio of paralytic \ncases to infections varies by serotype, ranging from approximately 1 in 190 infections for T ype 1 \nto approximately 1 in 1,900 infections for Type 2. Poliovirus is considered highly infectious and \nis spread through the fecal -oral or or al-oral routes. Fecal -oral transmission is considered the \nmost important pathway, particularly in settings with suboptimal hygiene and sanitation. Virus \nmay be present in the stool of infected persons for up to 6 weeks and sometimes longer. \nIndividuals who are asymptomatic can still shed virus and transmit it to others. \nInactivated polio vaccine (IPV) is the only polio vaccine that has been used in the US since \n2000. It contains inactivated poliovirus Types 1, 2, and 3. It cannot replicate, infect, or cause \ndisease. It induces effective humoral immunity and prevents paralysis. It also induces some \nnasopharyngeal mucosal immunity but does not provide substantial intestinal immunity or \nprevent gastrointestinal shedding. \nOral polio vaccine (OPV ) is no longer used in the US. It is a live-attenuated vaccine that can \ncome in different formulations. Trivalent vaccine (tOPV) c ontains poliovirus Types 1, 2, and 3. \nBivalent vaccine (bOPV ) contains Types 1 and 3 poliovirus. Monovalent OPV (m OPV ) contains \njust a single serotype. OPV replicates in the gut and is shed in the stool . It induces both humoral \nand mucosal immunity , so that it prevents paralysis and transmission of poliovirus. For this \nreason, it has been considered the historical vaccine of choice for countries experiencing polio \noutbreaks. However, the attenuated vaccine virus can revert to a neurovirulent form that causes paralysis. nOPV2 is a next-generation version of the Sabin Type 2 mOPV that was designed to \nbe more genetically stable and less likely to revert to a neurovirulent form. Between March 2021 and December 2023, almost a billion doses were administered as part of outbreak responses in \n35 countries under a WHO Emergency Use Listing (EUL) approval. As of December 2023, it \nearned WHO prequalification status. \n32 \n \n     \n    \n     \n  \n   \n   \n     \n \n \n   \n  \n \n    \n \n  \n \n \n    \n  \n   \n    \n \n \n \n   \n  \n \n   \n \n   \n  \n \n \n     \n  \n  \n \n  \n  \n  \n   \n \n \n \n    \n \n   \n In the US, the incidence of paralytic polio decreased rapidly after the introduction of the Salk \nIPV in 1955. The Sabin OPV was used for routine childhood immunization for decades , but an \nenhanced potency IPV was introduced in 1997 as part of a sequential schedule with OPV. In \n2000, the US moved to an IPV-only schedule. IPV has been the only polio vaccine \nrecommended in the US since that time. Wild poliovirus type 1 (WPV1) and vaccine- derived \npolioviruses are still circulating in certain parts of the world. Approximately 450 paralytic polio \ncases caused by WPV1 and circulating vaccine- derived polioviruses (cVDPV) that have been \nidentified in the last 12 months . \nA case of paralytic polio caused by VDPV T ype 2 (VDPV2) was confirmed in an unvaccinated \nyoung adult from Rockland County, New York on July 21, 2022. Genetic sequencing has indicated a linkage between this case to polioviruses collected in wastewater in Israel , the UK , \nand Canada. Of note, Rockland County has reported overall low vaccine coverage for over 20 \nyears. When this case was identified in s ummer 2022, only 60% of children under 2 years of \nage had received 3 doses of IPV . ZIP Code level coverage in the area was as low as 37% in \nsome areas. Fortunately, no additional paralytic cases were identified. \nPoliovirus related to the case was detected in wastewater in several New York State (NYS) \ncounties and in New York City (NYC) . Retrospective testing detected poliovirus in the area as \nearly as April 2022, indicating circulation and asymptomatic infections in the area since at least \nthat time. Related virus continued to be consistently detected in wastewater until the beginning \nof November 2022. The most recent detection was February 22, 2023, in Rockland County. \nSamples collected in the last year have all been negative. \nThe primary vaccination response to the 2022 outbreak was focused on identifying under -\nvaccinated and unvaccinated persons and providing catch-up vaccination with IPV. However, in \nfall 2022 when there were still wastewater detections of poliovirus, it was unclear whether the \nstrategy was going to be sufficient to interrupt circulation. WHO recommendations for polio \noutbreaks in countries like the US with exclusive IPV vaccination and high sanitation and \nhygiene are to conduct a timely outbreak response with IPV only if poliovirus transmission is \nconfined in a well -defined population group or geographic area. However, if transmission \npersists, WHO recommends considering an OPV response. Therefore, the work group was \nasked to discuss considerations for the potential use of nOPV2 as an outbreak response \nmeasure in the US. \nGiven that the New York outbreak had already waned at the time of the work group discussions, \nthe question the work group took up was a theoretical one, “S hould nOPV2 be used in \ncombination with a catch -up IPV campaign during a future Type 2 poliovirus outbreak in the \nUS?” The population under consideration would be persons living in an area with circulating \npoliovirus. The intervention would be nOPV2 vaccination for the general population in addition \nto catch-up IPV vaccination for un- or under -vaccinated persons. That would be compared to \nthe intervention of catch- up IPV vaccination only. The outcomes of interest were prevention of \nparalytic poliomyelitis; the extent and duration of poliovirus circulation in the community ; serious \nadverse events , including vaccine-associated paralytic polio; and possible introduction of a new \nVDPV2. \nThe work group used the ACIP EtR F ramework and domains to frame their discussions. Based \non the information presented, the work group had previously agreed that polio is a problem of \npublic health importance. For potential benefits and harms, the work group noted that there are \nhigh rates of seroconversion following 1 and 2 doses of nOPV2 when administered to infants. \n33 \n \n   \n  \n \n  \n  \n \n  \n  \n  \n   \n   \n \n \n   \n    \n    \n    \n     \n   \n \n  \n    \n \n \n   \n    \n  \n   \n   \n  \n \n \n  \n   \n   \n  \n   \n \n  \n   \n \n \n \n  \n  \n   \n  \n \n   \n  Given that vaccination with IPV is already recommended in this country, the main benefit of \nnOPV2 would be to confer gastrointestinal immunity. \nSabin OPV2 reduces the odds of fecal shedding following a subsequent oral challenge dose by \nmore than 90% compared to no vaccination. There are no direct data for nOPV2, but it has \nperformed as expected in the field in terms of slowing or stopping outbreaks. A small Phase 1 \nstudy among adults showed evidence of gastrointestinal immune response following nOPV2 \nadministration. It is known that nOPV2 is a live virus and it is shed in stool by nOPV2 recipients \nfollowing vaccination. When measured by PCR, 85% had detectable vaccine virus in stool at 7 \ndays . This decreased to 40% to 57% by 28 days. When measured by culture, which is probably \na better measure of infectious virus, 40% were shedding at 7 days . This decreased to 1% to \n14% by 28 days. \nnOPV2 was developed to be more genetically stable than Sabin OPV2 and less likely to regain \nneurovirulence in the laboratory . However, there is still a risk of vaccine- associated paralytic \npolio (VAPP) in recipients. The estimated risk of VAPP for nOPV2 is estimated to be 0.07 cases \nper million recipients or 1 case per 14.3 million recipients. This is compared to Sabin OPV with \nan estimated case rate of 0.25 to 4 cases per million recipients or 1 per 0.25 million to 4 million \nrecipients. The risk of VAPP is known to be highest in previously unimmunized children who are \nreceiving their first dose of OPV or in immunocompromised patients. And the risk of VAPP could \nbe mitigated by limiting nOPV2 administration to persons who had previously received at least 1 \ndose of IPV. It also is known that there is a risk of ongoing transmission of the nOPV2 virus with \nreversion to a VDPV. The risk is difficult to quantify, but so far, there have been at least 7 separate emergences of \nnew cVDPV2 linked to nOPV2 (cVPDV2-n) and at least 61 associated paralytic cases worldwide \nfrom these emergences. These are the numbers that have been published in the literature so \nfar, but the actual numbers are likely higher as nOPV2 use increases globally. However, nOPV2 \nis estimated to be 80% less likely than Sabin OPV to seed a new cVDPV2. The risk of a new \ncVDPV is highest when campaign coverage is low in a population with low immunity against \npolioviruses. \nWhen thinking about the balances of risks and harms for the individual recipient, most recipients \nwill have already been vaccinated with IPV during childhood immunization and are already \nprotected against paralytic disease. The anticipated benefits of nOPV2 to the individual recipient \nwould be a higher anti -polio Type 2 antibody titer and increased odds of mucosal immunity to \npoliovirus Type 2. For an under -vaccinated person, this would mean additional protection \nagainst paralytic disease. However, for a previously vaccinated person, there is unlikely to be a \nclinically significant benefit of vaccination. For potential harms, there is an extremely low but non-zero  risk of VAPP. There also is a risk of chronic infection if nOPV2 is given to a child with \nunrecognized immunocompromise. \nAt the population level, decreased transmission among nOPV2 recipients potentially could result \nin the outbreak ending earlier and fewer paralytic cases. Given that the vaccine virus can be \nshed in stool and transmitted to others, there likely would be some degree of passive \nvaccination of unvaccinated persons, which also would lead to decreased transmission and \nfewer paralytic cases. Potential harms at the population level include passive vaccination of the unvaccinated and a risk of VAPP among the unvaccinated, possible ongoing transmission of the nOPV2 virus leading to a new cVDPV2 virus , and possible chronic infection in \nimmunocompromised persons. \n34 \n \n     \n \n   \n  \n  \n  \n \n  \n  \n  \n    \n  \n  \n  \n \n \n    \n \n   \n    \n  \n    \n   \n \n   \n  \n  \n  \n \n  \n  \n   \n \n \n \n  \n   \n     \n    \n   \n \n   \n  \n  \n   \n    \n    \n   \n  The magnitude of these benefits and harms will depend on nOPV2 coverage and the extent of \nmixing between nOPV2 recipients , unvaccinated persons , and immunocompromised persons. \nDr. Kim Thompson and her colleagues at Kid Risk modelled the expected number of paralytic \ncases under different mixing scenarios for a cVDPV2 outbreak similar to the 2022 New York outbreak. They compared the number of cases expected with an IPV -only response to \nresponses that used a Sabin OPV2 or an nOPV2. In their model, they assumed that the number of vaccine doses administered was the same as the number of IPV doses that were actually \nadministered during the 2022 New York outbreak. They concluded that use of any type of OPV2 \nlikely would have ended transmission slightly earlier than with IPV alone. However, less than 1 \nadditional paralytic case was predicted in all IPV or OPV2 vaccine scenarios. They also ran a similar model for an aVDPV1 outbreak instead of aVDPV2 outbreak. Recall that Type 1 \npoliovirus infection is associated with a higher rate of paralytic disease than T ype 2. The results \nof this model suggested that use of an OPV1 would likely end VDPV1 transmission faster and \nresult in fewer paralytic cases than use of IPV alone. \nWhen assessing how substantial the desirable anticipated effects of nOPV2 would be on both \nthe individual and population levels, approximately half of the work group felt the desirable \neffects of using nOPV2 in addition to IPV were small. Some members felt that the desirable \neffects would be minimal , while some felt they would be moderate. When asked about the \nundesirable anticipated effects, the work group was evenly divided between minimal, small, and \nmoderate. When asked whether the desirable effects of nOPV2 would outweigh the undesirable \neffects, half of the work group felt that the desirable effects would not outweigh the undesirable \neffects, and that the information favored the use of IPV only. However, about 1/3 of the group \nfelt that it varies depending on the situation. \nMoving to resource use and feasibility , nOPV2 is not yet approved for use in the US. If the US \nwanted to use nOPV2, the mechanism for doing so would be the Expanded Access \nInvestigational New Drug Application (EA-IND), formally known as “Compassionate Use.” This \nrequires application to the FDA and FDA authorization. If implemented, the nOPV2 EA-IND \nprogram must include signed informed consent by vaccinees and/or their guardians, an enhanced system for monitoring vaccine safety, enhanced surveillance for possible VAPP \ncases and environmental surveillance for new VDPVs, and a system for tracking and accounting for every dose for containment purposes. This includes every dose given, every dose wasted, \nand doses returned. \nThe work group had a variety of opinions on whether this would be a reasonable and efficient \nuse of resources. Half of the work group responded that it was probably not a reasonable use of \nresources, but about 1/4 responded that it would vary depending on the specifics of the \nsituation. The work group also was divided about whether an nOPV2 campaign would be \nfeasible to implement. Half of the work group responded that it probably would be feasible, but \nabout a third responded that it probably would not be feasible. \nFor values and acceptability considerations, tOPV was removed from the US vaccination schedule in 2000 and was replaced with IPV because any risk of VAPP was deemed \nunacceptable at that time. This removal might be a barrier to acceptance of a new OPV vaccine \nin the future. In addition, the need for a signed informed consent likely will be a deterrent, \nespecially for those who are concerned about vaccine safety and new vaccines. It is unclear \nwhether the general public will accept an OPV vaccine if they are already protected from \nparalytic infection by IPV. It is unclear whether the general public will accept a vaccine to reduce \ncommunity transmission and risk to others if they would not benefit from it individually . \n35 \n \n    \n   \n \n \n  \n    \n \n   \n  \n  \n \n \n      \n    \n  \n   \n  \n \n   \n    \n  \n \n  \n   \n \n \n   \n \n \n  \n  \n  \n   \n    \n  \n  \n    \n  \n  \n \n    \n \n   \n     \n  \n   \n    \n     Similarly, it is unclear whether the populations most at risk (e.g., those with low childhood \nvaccination coverage and those with high rates of vaccine skepticism ) would accept an OPV \nvaccine. \nThe work group noted that perceptions of risk and vaccine acceptance might shift in an outbreak \nsetting, particularly if there is more than 1 paralytic case in a community. A clear majority of the \nwork group agreed that the target population probably does not feel that the desirable effects of \nnOPV2 are large relative to the undesirable effects. However, they were divided about whether \nthere was important uncertainty or variability in how much people would value the main \noutcomes. The work group was similarly divided about whether nOPV2 would be acceptable to \nkey stakeholders. Some felt that it probably would not be acceptable to stakeholders, some felt that it probably would be, and some felt that it would vary. \nIn terms of equity considerations , there is only 1 manufacturer of nOPV2, BioFarma in \nIndonesia, which is managed via a global stockpile. Supply shortages have occurred in the past. \nIn the US, IPV is readily available and provides protection against paralysis from cVDPV2. In \nmany countries with cVDPV2 outbreaks, there is limited protection against cVDPV2, unless \nthere are nOPV2 or Sabin OPV2 campaigns. In terms of equity within the US, the work group \nnoted that preventing transmission of the outbreak virus does protect unvaccinated, under-\nvaccinated, immunocompromised persons. Again, there was a spread of opinions among the \nwork group members. The plurality of the work group felt that using nOPV2 probably would not \nhave a significant impact on health equity. \nPutting it all together, most of the work group felt that the undesirable consequences of using \nnOPV2 during an outbreak in the US probably outweigh or are closely balanced with the \ndesirable consequences. \nIn summary, the work group believes at this time that the undesirable consequences of using \nnOPV2 probably outweigh or are closely balanced with the desirable consequences. The main \nconsiderations for the work group’ s interpretation was that IPV is readily available in the US and \nprotects against paralytic disease, and that the primary benefit of adding nOPV2 to an outbreak \nresponse would be to reduce transmission of outbreak virus and reduce risk of paralytic disease in under -vaccinated and immunocompromis ed persons. There were differences of opinion \nregarding the value of reducing asymptomatic transmission or ending asymptomatic transmission earlier during an outbreak. The work group was concerned about the extremely \nlow but non-zero risk of VAPP or new cVDPV2. There was uncertainty about public and \nstakeholder acceptance of a nOPV2 vaccine. However, the work group did acknowledge that \nthe balance of undesirable consequences compared to desirable consequences might shift in \nthe future depending on size and scope of the outbreak. As modeling showed, the calculus \nmight be different for a T ype 1 outbreak where more paralytic cases would be expected, and \npublic perception of risk might be higher. \nDr. Kidd then introduced the topic of fractional doses of IPV . Wild poliovirus Type 2 was \neradicated in 2015, prompting a global switch in April 2016 during which all the Sabin T ype 2 \nvirus was withdrawn from routine immunization. Countries that were still using OPV as part of \nroutine immunization replaced tOPV with bOPV that contains only Types 1 and 3. At the same \ntime, it was recommended that countries that still used OPV include at least 1 dose of IPV as \npart of their routine immunization schedule. Subsequently, based on clinical trial data and \nlimited IPV availability in some countries, WHO has supported the use of 2 fractional doses of \nIPV (1/5 full dose IPV) given intradermally in place of a single full dose. \n36 \n \n      \n   \n    \n \n  \n   \n    \n     \n      \n \n \n \n  \n    \n  \n \n   \n    \n   \n \n    \n  \n  \n  \n        \n   \n   \n   \n \n \n  \n  \n  \n \n \n      \n \n \n \n   \n   \n   \n \n  Clinical trials have shown that 1 fractional dose of IPV (fIPV) is less immunogenic than 1 full \ndose of IPV ; clinical t rial data also have suggested that 2 fractional doses are more \nimmunogenic than 1 full dose of IPV. \nCurrently, 6 countries representing about 20% of the global birth cohort use fIPV in their routine \nimmunization schedules (Bangladesh, Cuba, Ecuador, India, Nepal, Sri Lanka). They all use 2 \nfractional doses in combination with at least 3 bOPV doses. One example would be India’ s polio \nvaccination schedule in which a child would receive 5 doses of bOPV and 2 doses of fIPV. The \ncurrent US guidance recommends a total of either 3 or 4 doses of IPV, depending on the age of \nthe last vaccination. W hen assessing vaccine records for vaccines administered outside the US, \nthe guidance is that only tOPV doses or IPV doses are considered valid for the US vaccination \nschedule. If a child who was vaccinated under the India vaccination schedule immigrated to the \nUS and wanted to attend school in the US, current guidance is that none of their bOPV or fIPV \ndoses would be considered full doses. The child would need either 3 or 4 full IPV doses to be \nconsidered fully vaccinated against polio in the US. \nTherefore, the question for the work group was, “S hould 2 fIPV doses administered outside the \nUS be counted as either 1 or 2 doses toward the US vaccination schedule?” A meta-analysis \nwas conducted to update to the meta-analysis that was previously published in 2021. Overall, 2 fractional doses were associated with higher rates of seroconversion compared to 1 \nfull dose of IPV. Infants receiving 2 doses of fIPV were 1.5 times as likely to seroconvert \ncompared to infants who received 1 full dose of IPV. Moving to comparisons between 2 \nfractional doses and 2 full doses , 2 fractional doses were associated with slightly lower rates of \nseroconversion than 2 full doses of IPV. This especially is the case when administered at \nyounger ages. Peak antibody titers are also lower after 2 fractional doses compared to 2 full \ndoses. Based on this information, the work group group agreed with the following proposed \nlanguage to be included in CDC Clinical C onsiderations for persons receiving polio vaccines \noutside of the US : \nFor persons who received fractional (1/5 full dose) IPV administered intradermally \noutside of the United States, 2 fractional doses of IPV (fIPV) should be considered valid and counted as 1 full intramuscular dose of IPV toward the US vaccination schedule. \nIf a person received only 1 dose of fIPV, this dose should not be considered valid or counted toward the US vaccination schedule. \nFollowing discussion, several ACIP members expressed that they thought it was reasonable to accept 2 fractionated doses as 1 IPV dose and agreed with the work group’s recommendation. \nPUBLIC COMMENTS \nThe floor was opened for public comment on February 28, 2024, at 1:40 PM E ST. The \ncomments made during the meeting are summarized in this document. Members of the public \nalso were invited to submit written public comments to ACIP through the Federal eRulemaking \nPortal under Docket Number ID CDC-2024-0001. Visit regulations.gov for access to read \ncomments received. \n37 \n \n   \n \n \n   \n   \n \n \n   \n \n  \n   \n  \n  \n  \n \n \n  \n \n \n \n   \n    \n    \n   \n  \n \n \n    \n \n  \n  \n  \n \n \n \n \n \n     \n  \n  \n  \n    \n   \n  \n  \n  \n   Diana Olson \nNational Foundation for Infectious Diseases \nDiana Olson from the National Foundation for Infectious Diseases thanked the committee for its \nwork .  She highlighted the public health and economic benefits of COVID -19 vaccines but \npointed out that coverage with an updated 2023-2024 COVID -19 vaccine remains low . \nImmunization rates for other recommended vaccines also remained below public health goals. Only about half of US children and adults have received an influenza vaccine during the current \nseason and only about 22% of eligible adults aged 60 years and older and about 16% of eligible \npregnant women have received an RSV vaccine. Clearly, there is more work to be done to build vaccine confidence, address health disparities, and increase overall immunization rates. NFID \nsupports implementation of a Vaccines For Adults program to build upon the Vaccines for \nChildren and Bridge Access Program and further expand access to these lifesaving tools; \ncontinued support for US vaccine safety systems; and strong public health infrastructure to help \nensure that ACIP, CDC, and state and local public health agencies have the resources to do \ntheir important work. \nMr. Robert Blancato \nExecutive Director \nNational Association of Nutrition and Aging Services Programs \nMr. Blancato spoke as Executive Director of the National Association of Nutrition and Aging \nService Programs (NANASP) and on behalf of 18 other national aging and patient advocacy \nassociations , calling on ACIP to reverse your June 20 recommendation requiring shared \ndecision-making for the use of the new RSV vaccines for adults 60 and over. CDC has reported \nthat only 21.9% of adults and reported receiving the RSV vaccine; Mr. Blancato stated that this \nlow coverage was a consequence of ACIP’s recommendation with shared clinical decision-\nmaking, which he stated was difficult for health care providers to implement.  He stated that \nthese organizations also oppose shared decision-making due to its negative impact on \nvulnerable adults who are part of already underserved communities. He stated support for co -\nadministration of these vaccines and that he was encouraged by the morning’s discussion on \nthe recommendation for an additional COVID vaccine shot and the resulting amendment in favor of “should” instead of “may. ” If the goal is preventing serious health outcomes in older \nAmericans from respiratory illness, clear, broad, and easy to communicate guidance should be the standard for adult vaccines. \nMartha Nolan, JD Senior Policy AdvisorHealthyWomen \nMartha Nolan, Senior Policy Advisor for HealthyWomen, asked for clarification of \nrecommendations in several areas.  She expressed concern around how the seasonal \nrecommendations for maternal RSV vaccine translate to reimbursement and coverage. Specifically, many are confused about whether there is cost-sharing on the part of the patient if they receive the vaccine after January 31, 2024, b ecause the CDC guidance notes that in \ncertain US jurisdictions where RSV seasonality differs, providers may consider RSV vaccination \nafter January 31, but it is not clear if insurance will cover the cost. She asked that ACIP consider \nways to ensure there are no coverage barriers for patients, particularly when considering future seasonal recommendations. Lack of coverage for a vaccine is a barrier that often leaves patients to forego that care option. She expressed discouragement over the low uptake of RSV and COVID vaccines in older adults during the ‘ 23-‘24 respiratory season.  \n38 \n \n    \n \n \n \n \n \n \n    \n  \n    \n     \n    \n     \n   \n \n  \n  \n   \n  \n \n   \n \n \n \n  \n \n \n \n \n  \n \n  \n   \n     \n    \n  \n    \n  \n    \n  Despite there being many tools to protect ourselves against respiratory illnesses than ever \nbefore, there is also increasing confusion about who should receive what vaccine and when.  \nShe asked ACIP to evaluate existing guidance and provide necessary changes to ensure clarity \naround who should receive them and when and ensure coverage for all populations. \nHannah Berk \nUnaffiliated Community Member \nHannah Burke asked the committee to support the proposed recommendation on a booster \ndose of the COVID -19 vaccine in this meeting and to develop action steps to go further after this \nmeeting. She stated that people of all ages and health statuses need updated COVID vaccines \ncovered by insurance and/or public funds at least every 6 months. Twice annual vaccination \nallows healthy people to safely share space with high-risk family and friends so long as they \ntake precautions, which include vaccinating after immunity wanes significantly after 4 to 6 \nmonths and multiple COVID -19 infections compound systemic damage to the body that makes \nany person more vulnerable to illness and disability, even if they are otherwise healthy. She \nexpressed her hope that the committee will approve the proposal to announce COVID vaccine \nrecommendations on an earlier timeline this year, which can help ensure appropriate time to \nincrease the accessibility of these vaccin es. Ms. Burke shared that many of her friends and \nrelatives have asked their doctors about booster availability and have been told they don't need \nthe vaccine, and uninsured friends received their boosters months later than they could have because they hadn't heard about the Bridge Program .  She expressed her support for a “should” \nrecommendation on boosters for older adults and for an expedited vaccine decision-making \ntimeline. She urged the committee to make updated vaccines accessible twice annually for \npeople of all ages and at no cost and to recommend continued vaccination in the clearest, strongest terms. \nMaria Shreve, RN \nParents, Nurses, Herself \nMs. Shreve is a Registered Nurse and said that her family is so grateful to have access to \nchildren's COVID vaccines and now the new RSV vaccine, but it wasn't easy. She asked the \ncommittee to make children's vaccines available before school starts this year, which would help \ndecrease transmission and infection.  She said that children's uptake would be higher if supply was available and urged support for more accessible locations for kids of all ages , and mass \nvaccination clinics where parents can take kids of all ages for vaccines together instead of \ntaking one to a pharmacy, one to the pediatrician, and one to the Minute Clinic.  She said a \nbetter plan is quickly needed for the development and implementation of more RSV and COVID treatments . Unvaccinated children's hospitalization rates last year with COVID were as high as \nthe elderly, which could have been prevented by increased access to vaccines . She also \nexpressed support for options that allow access to vaccines every 6 months instead of yearly. \n39 \n \n  \n \n \n \n   \n    \n    \n     \n    \n    \n   \n \n    \n   \n     \n   \n    \n \n  \n    \n \n  \n    \n \n \n \n \n       \n  \n     \n \n  \n  \n  \n   \n   \n \n \n  \n  \n  \n \n \n \n    \n     \n    \n   \n  \n  AGENCY UPDATES \nCenters for Disease Control and Prevention \nDr. Demetre Daskalakis highlighted CDC’s work during the winter respiratory season. Influenza, \nCOVID -19, and RSV are still elevated in some parts of the country . As of February 10th, 22% of \nadults ≥18 years of age and 12% of children 6 months to 17 years of age have received COVID-\n19 vaccination. Pharmacies have administered over 750,000 doses of COVID -19 vaccines and \nover half a million doses were ordered by public health providers through the Bridge Access \nProgram. In the US, influenza vaccine coverage rates have decreased; about 6.5 million doses \nof influenza vaccine have not been given this season compared to last. \nThe ACIP was a very important part of RSV vaccine launches for pregnant people and \nimmunization launches for newborns. Despite an initial supply and demand mismatch with \nnirsevimab, 30% of infants <8 months of age received nirsevimab and about 16% of eligible \npregnant persons received an RSV vaccine between 32 and 36 weeks gestation. In the context \nof new vaccine products, this is remarkable uptake. \nAs of February 22 , 2024, a total of 35 cases of measles have been reported this year in 15 \njurisdictions compar ed to 58 cases of measles last year in 20 jurisdictions in the US. This is not \na good slope of the curve, particularly given that measles is preventable with safe and effective \nvaccines. As measles continues to increase in other parts of the world, importations continue to \nhappen. When importations occur in places where coverage is low, there is risk for ongoing \nlarger outbreaks. \nCenters for Medicare and Medicaid Services \nMary Beth Hance began by announcing the passing earlier in the month of Dr. Jeffrey Kelman \nfollowing an illness. Dr. Kelman was a Centers for Medicare and Medicaid Services (CMS ) \ncolleague who was the C hief Medical Officer for CMS ’s Center for Medicare. He was involved \nwith the ACIP for many years, representing CMS on many work groups . Dr. Kelman was a \npulmonologist by training, which fit perfectly into much of the work he did supporting CMS on \nthe influenza, pneumococcal, COVID, and many other ACIP work groups. He also worked \nclosely with FDA on using data and was absolutely committed to the idea that valuable data \nwithin agencies could be used across agencies . Dr. Wharton and other colleagues in \nattendance mourned the loss of Dr. Kelman and acknowledged his many important \ncontributions . \nIn terms of updates, on February 12, 2024, CMS issued an updated Medicaid and CHIP vaccine \ntoolkit that reflects the change in commercialization of COVID vaccines and the Inflation \nReduction Act provisions that impacted mandatory coverage of vaccines for adults in Medicaid. \nFood and Drug Administration \nDr. David Kaslow reported that since the last FDA agency report during the October 2023 ACIP \nmeeting and apropos of discussions earlier in the day on chikungunya, FDA approved IXCHIQ®, \na vaccine indicated for the prevention of disease caused by chikungunya virus in individuals ≥18 \nyears of age who are at increased risk of exposure to chikungunya virus ( CHIKV ). This \nindication was approved under accelerated approval based on anti -CHIKV neutralizing antibody \ntiters. \n40 \n \n   \n  \n    \n      \n \n \n    \n  \n    \n \n  \n   \n  \n \n    \n   \n \n  \n  \n \n   \n  \n  \n \n \n \n   \n   \n  \n \n  \n  \n    \n  \n   \n \n \n \n  \n  \n  \n \n \n   \n  \n   \n    \n  Continued approval for this indication may be contingent upon verification and description of \nclinical benefit in confirmatory studies. The highlights of the US prescribing information include \nwarnings and precautions that IXCHIQ® may cause severe or prolonged chikungunya- like \nadverse reactions. Other regulatory actions include scores of supplemental Biological License \nApplications (sBLAs), some pertaining to manufacturing changes and some regarding labeling \nchanges. \nGiven the ACIP agenda for the next day , Dr. Kaslow highlighted the work FDA continues to do \nto monitor the safety and effectiveness of vaccines for respiratory illnesses using the Biologics \nEffectiveness and Safety System (BEST) and the CMS System. Ongoing projects include safety \nand effectiveness of RSV vaccines, influenza vaccines, and COVID -19 2023-2024 formula \nvaccines. Although the Vaccines and Related Biological Product Advisory Committee \n(VRBPAC) has not met since the October 2023 ACIP meeting, FDA anticipates convening \nVRBPAC twice before the June 2024 ACIP meeting. The VRBPAC is scheduled to meet on \nMarch 5, 2024, in open session to discuss and make recommendations on the selection of \nstrains to be included in the influenza vaccine for the 2024-2025 influenza season. As \nmentioned earlier in the day, VRBPAC is scheduled to meet in open session on May 1 6, 2024, \nto discuss and make recommendations on the selection of strains to be included in the 2024-\n2025 formula for COVID -19 vaccines. Other convenings of VRBPAC may occur as needed. As \nin the past, Dr. Kaslow took the opportunity to personally thank the review teams, their \nsupervisors, and management at Center for Biologics Evaluation and Research (CBER) who \nworked and continue diligently to conduct research and review to protect and enhance public \nhealth. In addition, he thanked CDC staff for their many contributions and their collegial support \nof collective efforts to protect and enhance public health for immunization. \nHealth Resources and Services Administration \nCDR Reed Grimes, MD, MPH provided the Health Resources and Services Administration \n(HRSA) update the National Vaccine Injury Compensation Program (VICP ) continues to actively \nprocess claims . In Fiscal Year 2024, as of January 1, petitioners have filed 314 VICP claims. \nOver $41 million was awarded to petitioners and over $13 million was awarded to pay attorney ’s \nfees and costs. In addition, the VICP had approximately 600 claims alleging vaccine injury \nawaiting activation for review. Previously, there was nearly a 12-month wait period between \nwhen a petition was found to have adequate medical records to review by a HRSA provider and \nwhen a review was completed. As of January 1, 2024, the wait period has been reduced to less \nthan 1 month. More data about the VICP can be found on its website at www.hrsa.gov/vaccine-\ncompensation/data/index.html . \nIn the decade prior to COVID -19, fewer than 500 claims had been filed with the \nCountermeasures Injury Compensation Program (CICP ). CICP received a direct appropriation \nfor the first time in Fiscal Year 2022, and the program has used those funds to increase its \ncapacity to conduct medical reviews by hiring and training new review staff and contractors as well as to pay compensable claims and improve IT and other communications with requesters. As of January 1, 2024, 12,854 claims alleging injuries or death from COVID -19 \ncountermeasures had been filed with the CICP, including 9,682 claims alleging injuries or death \nfrom COVID -19 vaccine. CICP has rendered decisions on 2,214 COVID -19 claims as of \nJanuary 1, 2024, representing more than 4 times in the prior decade. More information about \nthe CICP can be found at its website at www.hrsa.gov/cicp . \n41 \n \n  \n \n    \n     \n  \n \n \n \n     \n     \n     \n   \n  \n    \n \n \n \n \n \n  \n \n  \n  \n \n  \n \n \n \n \n     \n   \n     \n \n  \n   \n \n \n  \n  \n  \n   \n  \n  Indian Health Services \nMatthew Clark, MD, FAAP, FACP reported that the Indian Health Service (HIS) continues to \nprioritize vaccination as its principal clinical and public health prevention priority. As part of the \nIHS National E3 Vaccine Strategy, the IHS seeks to ensure that every patient at every \nencounter is offered every recommended vaccine when appropriate. Following announcement of this IHS strategic initiative in November 2022, the IHS established the E3 Vaccine Champions Pilot Program in March 2023. Since then, the IHS has designated 28 vaccine \nchampions pilot sites in 9 of the 12 IHS areas, including federal, tribal, and urban programs. IHS \nhas shared clinical and community resources and multidisciplinary best practices to cross -\npollinate the IHS system of care and to improve vaccine coverage rates in tribal communities. \nAs part of a proactive strategy of outreach, education, and engagement with its partners in tribal \ncommunities, the IHS 2023-2024 Respiratory Viral Vaccine Campaign has worked to ensure timely access to immunizations for COVID, seasonal influenza, and RSV among its vulnerable \nservice population across the age spectrum. \nFollowing reported supply chain constraints in the fall, IHS worked diligently to secure a \nsupplemental supply of the long-acting monoclonal antibody, nirsevimab, to ensure that this life-\nsaving immunization was available in support of ACIP recommendations for administration of \nnirsevimab to AI/AN infants and children up to 19 months of age. To date, nearly 8,000 supplemental doses of nirsevimab have been distributed and administered to mitigate the risk of serious RSV disease among infants and children in Indian Country. Due to persistently elevated rates of respiratory viral illness in Indian Country, in collaboration with IHS obstetric and \npediatric subject matter experts (SMEs), last month the IHS Chief Medical Officer, Dr. Loretta \nChristensen announced extension of the period for administration of maternal RSV vaccine to \neligible pregnant AI/AN persons through the end of February for this season in seeking to \nmitigate the risks of RSV in IHS’s high-risk service population. Preliminary surveillance suggests favorable uptake of novel RSV countermeasures in Indian Country. This is especially true in regions historically most impacted by high rates of RSV -related morbidity and mortality, such as \nthe YK Delta Region in Alaska, where proactive efforts by tribal partners included bush plane flights to over 25 vil lages to administer nirsevimab to eligible infants and children, many of \nwhom also received other ACIP recommended vaccines. Moving forward in collaboration with its partners in tribal communities, IHS will continue to promote access, quality, value, and equity related to immunizations in Indian Country. \nNational Institutes of Health \nDr. John Beigel provided several updates from the National Institute of Health (NIH) on vaccine-\nrelated research of interest to the ACIP. Regarding NIH leadership, In November 2023, Dr. \nMonica Bertagnolli started as the 17\nth Director of the NIH. She is the first surgeon and second \nwoman to hold the position. Nominated by President Biden, she was confirmed on a bipartisan \nbasis in the US Senate and transitioned from her role as Director of the National Cancer \nInstitute (NCI) , a position she held since October 2022. \nFor COVID -19, Dr. Beigel highlighted 2 studies about the value of maternal vaccine. First was a \nstudy that demonstrated maternal vaccination may prevent infant COVID -19 in a cohort. Study \nresearchers aimed to quantify protection against infection from maternally -derived vaccine \nantibodies in the first 6 months of an infant’ s life. Higher transplacental binding and neutralizing \nantibodies substantially reduced the COVID -19 infection in the infants. Until infants are age-\neligible for vaccination, maternal vaccination provides passive protection against symptomatic \ninfection during early infancy. \n42 \n \n  \n  \n  \n     \n   \n \n \n \n   \n    \n \n    \n \n \n \n \n  \n    \n  \n   \n \n  \n \n      \n   \n   \n     \n  \n   \n \n \n \n \n    \n   \n \n   \n   \n  \n   \n \n   \n \n \n   \n \n  These same findings extend to preterm infants. In a separate study, it was shown that preterm \ninfants born to people who are vaccinated for COVID-19 have roughly the same antibody titers \nas those of term infants. Moreover, in all infants, antibodies to the spike protein were higher \namong those born to individuals who received 3 or more vaccines before delivery compared to \nthose who only had 2 . These findings may help allay concerns that fewer antibodies might pass \nfrom preterm infants compared to term infants. \nIn a study regarding the ancillary benefits of COVID -19 vaccines versus a prospective cohort \nstudy of adults , researchers identified SARS- CoV-2 infections and followed them for the \npresence of post-acute sequelae. COVID vaccination not only prevented disease, but also was \nassociated with lower prevalence and severity of long COVID symptoms. There also was an \ninteresting study about looking at the spike in preterm birth rates that started at the beginning of \nthe pandemic. That analysis showed that by late 2022, widespread COVID-19 vaccination in \npregnant people likely halted the spike in preterm infants, and those rates have come down \ntoward normal. This underscores the need for pregnant people to keep current on COVID -19 \nvaccination. \nIn October 2023, the Nobel Prize for Physiology or Medicine was awarded to Drew Weissman, \nMD, PhD and Katalin Karikó, PhD for their work on messenger ribonucleic acid (mRNA) that \nenabled the development of mRNA vaccines . Dr. Weissman and Dr. Karikó had decades long \nwork on mRNA with incremental steps in the science. Ultimately, those steps and those \nscientific advancements were critical to enable the unprecedented development of the mRNA \nvaccines that stemmed the pandemic. \nFor influenza, Dr. Beigel highlighted a study that evaluated 2 doses of high-dose trivalent \ninfluenza vaccine (HD-TIV) compared to standard dose quadrivalent influenza vaccine in a \npediatric hematopoietic stem cell transplantation (HSCT) population. The high-dose vaccine \nresulted in higher antibody responses, especially for influenza A. Because influenza causes \nsubstantial morbidity and mortality in that population, optimization of vaccine strategies is \ncritical. The use of high- dose inactivated vaccines may be a practical strategy to overcome the \npoor immunogenicity in that population. \nOffice of Infectious Disease and HIV/AIDS Policy \nCDR Valerie Marshall reported that the Interagency Vaccine Working Group (IVWG) of the HHS \nis scheduled to convene in March 2024 to deliberate on an interagency progress report which \naddresses the achievements and strides made from 2021 to 2023 toward achieving the goals \noutlined in the Vaccines National Strategic Plan (VNST). This collaborative effort underscores \nthe commitment of multiple federal agencies toward transparent communication and the pursuit of vaccination goals. The National Vaccine Advisory Committee (NVAC) held a meeting on \nFebruary 22 -23, 2024, to discuss critical policy matters related to vaccination. The committee’ s \ndeliberations included a discussion on the resurgence of measles cases, which underscored the pressing need for proactive public health measures to improve vaccine confidence and counter \nmisinformation about vaccines. \nWith no additional business posed for the day , the ACIP meeting stood in recess until 8:00 AM \non February 29 , 2024. \n43 \n \n  \n \n \n \n \n \n  \n   \n  \n   \n \n    \n \n   \n \n   \n     \n    \n   \n \n \n \n  \n \n  \n    \n   \n   \n   \n \n \n   \n   \n  \n \n     \n  \n \n    \n    \n  \n   \n    \n  \n  \n   \n THURSDAY:  FEBRUARY 2 9, 2024 \nWELCOME AND INTRODUCTIONS \nCall to Order/Roll Call \nDr. Melinda Wharton (ACIP Executive Secretary & Acting Chair, CDC) called to order and \npresided over the February 28-29, 2024 ACIP meeting because the process for the new ACIP \nChair to join the committee had not yet been completed. As allowed under the ACIP charter, the ACIP’s six Ex Officio members were temporarily designated as voting members. She then \nconducted a roll call, which established that a quorum was present. A list of Members, Ex \nOfficios , and Liaison Representatives is included in the appendixes at the end of this summary \ndocument. No COIs were identified for the second day of this meeting. \nRESPIRATORY SYNCYTIAL VIRUS (RSV) VACCINES ADULTS \nDr. Camille Kotton, Chair, ACIP Adult RSV Work Group, introduced the RSV session, reminding \neveryone that in June 2023 ACIP recommended that adults ≥60 years of age may receive RSV \nvaccination using shared clinical decision -making. There are currently 2 licensed and \nrecommended products for adults ≥60 years of age: \nGSK RSV vaccine (AREXVY), which is a 1-dose adjuvanted (AS01E) recombinant prefusion \nF (preF) protein vaccine. \nPfizer RSV vaccine ( ABRYSVO\n®), which is a 1-dose recombinant preF vaccine. \nIn October, GSK presented data to the ACIP demonstrating that the humoral immune response to a single dose of GSK RSV vaccine in adults 50─ 59 years of age was non-inferior to that in \nadults >60 years of age. The ACIP Adult RSV Work Group shared their early interpretations of \nthis data and the potential role of RSV vaccination in adults younger than 60 years of age, \nincluding subpopulations who would benefit most from vaccine and equity implications. At that \ntime, ACIP members expressed the importance of reviewing safety surveillance data to inform future preferred policy recommendations. \nThe work group has been simultaneously reviewing additional data to prepare for the upcoming \npolicy decisions, especially focusing on the risk of severe RSV disease in adults 50 ─59 years of \nage, especially those with chronic medical conditions ; RSV vaccine uptake among different \ndemographic groups ; and potential policy options that would transition away from shared clinical \ndecision-making. The work group also has begun reviewing data from Moderna on their \ninvestigational RSV vaccine (mRNA -1345) in adults ≥60 years of age. \nDr. Rituparna Das (Moderna) presented clinical data on Moderna’ s investigational RSV \ncandidate vaccine, mRNA -1345, among adults ≥60 years of age. The data package on adults \n≥60 years of age was submitted to the FDA for review in September 2023. The i nvestigational \nRSV v accine, mRNA -1345, is a lipid encapsulated mRNA -based vaccine that encodes the RSV \nfusion (F) glycoprotein stabilized in the prefusion confo rmation. The prefusion F protein contains \nepitopes that elicit antibodies that are potently neutralizing and cross-reactive between RSV-A \nand RSV -B. Following administration of a single 50 microgram (μg) dose, robust \nimmunogenicity was observed in Phase 1 that was persistent through 12 months post-\nvaccination. \n44 \n \n    \n   \n     \n   \n    \n \n   \n     \n     \n  \n \n    \n      \n \n \n    \n  \n   \n \n   \n   \n \n   \n    \n  \n    \n  \n \n  \n  \n   \n    \n  \n        \n   \n   \n  \n   \n \n \n \n   \n    \n   \n \n  \n    \n     \n    \n   \n  The pivotal Phase 2/ 3 safety and efficacy trial, Study 301, enrolled adults ≥60 years of age. \nParticipants were randomized 1:1 to receive mRNA -1345 or saline placebo and 24 months of \nplanned follow-up. Randomization was stratified by age (60─74 years and ≥75 years) and \npresence or absence of congestive heart failure (CHF) or COPD . The study started in \nNovember 2021 and weekly surveillance was conducted via electronic diary to look for RSV \nsymptoms. Given the importance of risk factors on morbidity and mortality with RSV in older \nadults, participants also were included with a number of high-risk medical conditions. Frailty \nstatus was assessed of all participants at entry using the Edmonton Frail Scale (EFS). \nParticipants were characterized on a 0- to 17-point scale as being fit (0-3) , vulnerable (4-5), or \nfrail (6-17). \nA total of 36 ,550 participants were enrolled as of the April 30, 2023 data cutoff, a pproximately \n50% of whom came from the US. V accinations in Study 301 began in late November 2021 and \ncontinued through December 2022. The primary analysis was driven by the accumulation of a \ntarget number of cases, and study success was declared at that time. The study continued in a blinded fashion. When nearly all study participants reached 6 months of follow -up, an additional \nanalysis was conducted as agreed with the FDA. The median follow -up for this additional \nanalysis was almost 9 months, with a range up to 17.7 months. \nThe demographics of Study 301 were well -matched between the vaccine and placebo \nrecipients. The median age was 67 years , 30% of the study participants were 70─ 79 years of \nage, just under 3,000 participants were ≥80 years of age, 12% were Black or African American, \nand 33% identified as Hispanic or Latino. R ace/ethnicity in the study was representative of the \nUS population. Approximately 2,600 participants had CHF or COPD , almost 1/3 of trial \nparticipants had 1 or more of the comorbidities that put them at higher risk for RSV -related \nmorbidity or mortality , 16% percent of the population was considered vulnerable, and 6% were \nconsidered to be frail. \nThe median safety follow -up was 8.6 months and almost all participants had been followed for \nmore than 6 months. In general, mRNA-1345 was well -tolerated. Injection site pain was the \nmost common local reaction, followed by axillary swelling or tenderness. Most events were mild, \nwith onset within 1 to 2 days post-injection and lasting 1 to 2 days. Solicited systemic reactions \nof fatigue, myalgia, and headache were the most common. Fever was rare and most reactions \nwere mild, with onset within 1 to 2 days post-injection and lasting 1 to 2 days. Severe events \nalso were rare. Unsolicited events were well -balanced overall between vaccine and placebo \nrecipients . The occurrence of SAEs, AEs leading to discontinuation, and AESIs also were \nbalanced between vaccine and placebo recipients. There was 1 event in the vaccine group, \nwhich was aspiration following intoxication. There were 6 fatal events in the placebo group. \nThere were no cases of Guillain -Barré syndrome ( GBS) or acute disseminated \nencephalomyelitis ( ADEM). There was no imbalance in neurological disorders such as Bell ’s \npalsy or facial paralysis. For cardiac events, there was no imbalance in cardiac arrhythmias, \nincluding atrial fibrillation. No myocarditis was identified in vaccine recipients and there were no \ncases of pericarditis with onset within 6 weeks of vaccination. \nCo-primary endpoints were protection against RSV -lower respiratory tract disease (RSV -LRTD) \nwith ≥2 or ≥3 signs and symptoms. Protection against RSV -associated acute respiratory \ndisease (ARD) and RSV -related hospitalizations were key secondary endpoints. RSV-LRTD \nwas defined as new or worsening of ≥2 or ≥3 of signs/s ymptoms for ≥24 hours and RSV -ARD \nwas defined as new or worsening of ≥1 s igns/s ymptoms for ≥24 hours. Identification of a \nsymptom prompted a visit to the site and a nasopharyngeal swab. \n45 \n \n   \n    \n \n    \n   \n     \n     \n    \n   \n \n   \n     \n    \n \n     \n \n   \n  \n   \n   \n          \n    \n \n       \n \n \n     \n   \n    \n   \n  \n  \n      \n  \n \n \n \n     \n  \n   \n    \n    \n    \n   \n  \n \n \n  All cases had to be confirmed for RSV by reverse transcription polymerase chain reaction (RT -\nPCR). C ontinuous year -round weekly surveillance was conducted throughout the study. \nThe target number of cases for the first analysis was met in November 2022 which became the \nprimary analysis. Follow -up was a median of 3.7 months , with a range from 0.5 to 12.6 months. \nThe efficacy against RSV -LRTD with ≥2 symptoms was 83.7% (66.0%, 92.2%) and efficacy \nagainst RSV-LRTD with ≥3 symptoms was 82.4% (34.8%, 95.3%). Efficacy against RSV-ARD, \nthe secondary objective, was 68.4% (50.9%, 79.7%). The observed RSV cases were subtyped \nfor RSV-A and RSV-B, with efficacy observed for both RSV -A and RSV -B. \nEfficacy was maintained in older ages and was similar for those with or without co-morbidities and in those who were considered vulnerable or frail. There were no hospitalizations in the \nprimary analysis. For LRTD with shortness of breath as a marker of severity, efficacy was \n86.7%. For RSV cases that were medically attended in the emergency department or urgent \ncare, there were 5 cases in placebo recipients and no cases among vaccine recipients. \nAn additional analysis of efficac y was conducted at the end of April 2023; the median follow-up \nwas 8.6 months , with the upper bound of the range being 17.7 months. The efficacy of mRNA -\n1345 against RSV -associated LRTD and ARD remained high, with overlapping confidence \nintervals to the primary analysis estimates over this longer follow-up time. V E against LRTD with \n≥2 symptoms and ≥3 symptoms was 63% (48.7%, 73.7%) and for ARD was 54% (40.5%, \n64.3%). Protection was seen for both RSV-A and RSV-B. \nEfficacy was consistent for adults 60 ─69 years of age and 70 ─79 years of age. Among adults \n≥80 and older, there were only 11 cases of LRTD with ≥2 symptoms , precluding the \nconclusions. The group of adults ≥ 80 years of age had the lowest incidence of RSV in the \nplacebo recipients compared to adults 60─69 years of age and 70─ 79 years of age, perhaps as \na carryover of pandemic measures in these trial participants. Efficacy in participants with co-\nmorbidities and participants who were vulnerable or frail also were very consistent in this \nanalysis. Assessing the impact of mRNA -1345 on preventing severe RSV as indicated by the \nshortness of breath measure, efficacy was 74.6% (50.7%, 86.9%). More participants in the \nplacebo groups sought a higher level of care in an ED or UC , with efficacy of 61.8% (-7.35, \n86.45) . A total of 2 participants were hospitalized, a 73-year -old and an 84 -year-old, both of \nwhom had asthma and were from the placebo group. There were no hospitalizations in the \nvaccine group. \nThe vaccine was immunogenic , result ing in an 8- fold rise in the RSV -A neutralizing titers and a \n5-fold rise in the RSV -B neutralizing titers. Responses were consistent across the age spectrum \nand there was no evidence of decreasing response as age increased . Cellular immune \nresponses were evaluated for CD4 and CD8 in a separate study of adults 50─ 75 years of age. \nThe vaccine was found to elicit strong and persistent T-cell responses as well. In the Phase 1 \nstudy, antibody remained detectable at 12 months, w ith GMTs 2-to 3-fold over baseline for both \nRSV-A and RSV-B. In that study, re- vaccination at 12 months was evaluated. Administration of \na second dose of mRNA -1345 increased both RSV -A and RSV-B neutralizing titers 5-to 7-fold. \nThe question of re-vaccination is important since protection from RSV by natural infection is not \nlifelong, but additional durability data will be needed to determine the timing. Moderna is \nstudying re- vaccination at 1 and 2 years in Phase 3 studies. \n46 \n \n     \n \n    \n   \n  \n \n    \n   \n   \n \n \n   \n   \n   \n \n \n    \n    \n \n \n  \n    \n    \n  \n \n     \n  \n      \n   \n      \n   \n \n   \n \n  \n   \n  \n   \n   \n \n   \n  \n \n   \n  \n  \n  \n Co-administration was explored with standard-dose quadrivalent influenza vac Ccine (Afluria) \nand the Moderna bivalent COVID -19 vaccine in adults ≥50. Concomitant administration of the \nRSV and influenza vaccines was immunogenic for RSV -A, RSV-B, and all 4 influenza types and \nwas well -tolerated in terms of local and systemic reactions. The same trend was observed with \nconcomitant administration of mRNA -1345 and COVID -19 vaccine. \nTo summarize, the mRNA -1345 vaccine was well-tolerated in over 19,000 adults ≥60 years of \nage. No cases of GB S, ADEM , or other safety concerns were identified. The vaccine was shown \nto be efficacious , met all pre-specified criteria for licensure, and continued to be efficacious \nthrough a median of 8.6 months with a range up to 17.7 months. The vaccine prevented severe \nRSV disease as evaluated by the prevention of shortness of breath and medically -attended \nAEs. Strong antibody and cellular immune responses were seen through 12 months, and \nboosting was evident at 1 year. The antibody responses were similar across age groups, \nincluding those ≥ 80 years of age. Pre-specified immunogenic criteria were met, and no new \nsafety signals were seen with concomitant administration. \nDr. Daley observed that VE was lower in the later data than the earlier data and asked Dr. Das \nto expand on how the results were interpreted for the durability of a single dose. \nDr. Das indicated that durability of a single dose was assessed in several ways . The confidence \nintervals at both time points overlap ped. A detailed time-to-event (TTE) analysis was performed, \nwhich was reassuring in that the cases that were occurring in the longer follow -up were not in \npeople who were vaccinated earlier. Efficacy also was consistent in a before 6 months and after \n6 months analysis. Perhaps there is some waning, but there also is an effect from underlying \nforce of infection.  Immune responses lasting out to 12 months are also reassuring. Dr. Long said that regarding the immunogenicity of the second dose at 1 year, “boost” is a word \nthat could be used. “Reinforcing might be another word. However, no data were shown to \nsuggest that there was an anamnestic response. Since the GMTs after the second dose did not \nquite equal the titers after an initial dose in the mRNA vaccines against COVID and influenza, \nshe wondered whether a similar lack of robustness was observed after a second dose or if this \nspecific to RSV and if there were any ideas about why this is different. Dr. Das responded that for RSV, there is still a highly seropositive population. While a good \nresponse was observed in these small studies, both 1 and 2 years are being examined to \ndetermine whether there is any benefit to a 2-year gap. In terms of COVID -19 vaccines, the \nboosts have gone higher than the initial vaccination, but the immunologic experience with \nCOVID at the point that those studies were conducted was quite different and it may not be \ncompletely fair to put those vaccines side-by -side. To reiterate, persistent immune responses \nare observed through 12 months. While boosting is observed with a second dose, it does not \nrecapitulate the original dose, but it is quite close. Again, Moderna will be bringing the larger \nstudies forward for both 1-year and 2-year revaccination later in 2024. \nDr. Beigel (NIH) asked whether Moderna had thought about or started work on correlates of \nprotection to help understand what titers are actually needed. \nDr. Das responded that Moderna is very well -positioned to perform a correlates of protection \nanalysis since samples were collected from every person in this study at baseline and Day 29. \nInitial analyses have been performed of the correlates, which show that RSV neutralizing titers \nare very well -correlated with protection. These data are being investigated in more detail to look \nfor whether a threshold can be determined. \n47 \n \n   \n  \n \n  \n  \n  \n \n  \n \n   \n \n \n \n   \n  \n   \n \n \n   \n  \n  \n \n    \n   \n \n  \n  \n  \n    \n   \n  \n \n  \n    \n  \n   \n    \n   \n \n   \n   \n       \n   \n  \n   \n   \n  \n  Rebecca C. Woodruff, PhD, MPH (CDC/NCCDPHP) presented preliminary results exploring \nchronic conditions as risk factors for RSV -associated hospitalizations. Using methods \ndeveloped for a previous study, 3 data sources were leveraged to calculate RSV hospitalization \nrates during the 2017-2018 RSV season stratified by chronic condition and age group. The data \nsource for the numerator was RSV -NET and the data sources for the denominator were the \nBRFSS and Census county -level population estimates. \nRSV-NET is a population-based hospitalization surveillance platform. Currently, RSV -NET \nconducts active population-based surveillance of laboratory -confirmed RSV-associated \nhospitalizations for more than 300 acute care hospitals in 58 counties across 12 states (Oregon, \nCalifornia, Utah, Colorado, New Mexico, Minnesota, Michigan, New York, Connecticut, \nMaryland, Tennessee, Georgia) . This area includes about 8.6% of the US population. In the \n2017-2018 surveillance season, the catchment area was slightly small er. It included about 38 \ncounties across 8 states. Hospitalizations reported to RSV -NET include all of those where a \npositive RSV test was reported within 14 days prior to or during hospitalization. Testing for RSV \nis driven by clinical judgment and facility policies. \nThe BRFSS is an annual CDC -funded telephone- based health survey that operates in 50 US \nstates, DC, and 3 US territories. BRFSS uses both landlines and cell phone numbers for \nsampling and collects about 400,000 interviews of adults each year. The questionnaire \nassesses a variety of health-related characteristics, including self-reported history of select \nchronic conditions. The BRFSS sample is designed to represent the civilian community -dwelling \nadult population ≥18 years of age in each jurisdiction. Adults who are not community -dwelling, \nincluding those living in nursing homes or other LTCFs , are not eligible to participate. \nThe study evaluated 9 chronic medical conditions as potential risk factors for RSV-associated \nhospitalization, including a sthma; chronic kidney disease (CKD); c hronic obstructive pulmonary \ndisease (COPD), coronary artery disease (CAD) , current smoking, diabetes mellitus , obesity \n(body mass index 30-39 kg/m2), severe obesity (body mass index ≥40 kg/m2), and s troke. This \nlist was determined based on chronic conditions that were abstracted by RSV -NET and included \nin the BRFSS questionnaire. \nRSV hospitalization rates were calculated using RSV-NET data to obtain counts of RSV \nhospitalizations among community -dwelling adults ≥50 years of age with and without chronic \nmedical conditions of interest. These counts served as the numerator data in the rate \ncalculation. To align with the BRFSS data, RSV -NET cases were excluded among adults living \nin nursing homes or other LTCFs . Next, a combination of BRFSS and the C ensus data were \nused to obtain estimated counts of community -dwelling adults ≥50 years of age with and without \nchronic medical conditions for the 38 -county RSV -NET catchment area, which served as the \ndenominator data for the rates. These data were used to calculate RSV hospitalization rates per \n100,000 population among adults with and without each chronic medical condition, which was \nsummarized by 3 age groups : 50─ 64 years of age, 65─ 74 years of age, and ≥75 years of age. \nFinally, rates were multiplied by burden multipliers to account for the under-detection of RSV \namong hospitalized adults and sensitivity of diagnostic tests. To calculate the rate ratios, the \nRSV-associated hospitalization rates in adults were divided with versus without chronic medical \ncondition overall and within each age group. Monte Carlo simulation and generalized Poisson \nmodels were used to estimate rate ratios and 95% Monte Carlo intervals after adjusting for sex \nand race or ethnicity group. \n48 \n \n      \n   \n    \n    \n     \n  \n \n      \n       \n    \n    \n   \n  \n   \n \n  \n  \n     \n  \n    \n  \n \n \n  \n   \n   \n  \n   \n  \n \n   \n  \n    \n  \n \n   \n  \n    \n    \n  \n    \n \n    \n   \n  \n   \n \n       \n      \n    \n  For adults 50─64 years of age, the RSV hospitalization rate was about 7.9 times higher for \nadults with versus without CKD, 5.8 times higher for adults with COPD, about 4 times higher for \nadults with severe obesity or CAD, and about 2 to 3 times higher for adults with asthma, \ndiabetes , and current smokers. The RSV hospitalization rates were similar for adults regardless \nof obesity or history of stroke. To put these rates into the context, adults ≥75 years of age have \nsubstantially higher hospitalization rates compared with adults 50─ 60 years of age. \nFor adults 65─74 years of age, the rates were higher across the board than for adults 50─ 64 \nyears. There also was a generally similar pattern with RSV hospitalization rates at about 6 times \nhigher for adults with CKD, 4.5 times higher for adults with severe obesity, 4.2 times higher for \nadults with COPD, and 2 to 3 times higher for adults with asthma, current smokers , CAD, or \ndiabetes. For context, the RSV hospitalization rate was about 6.1 times higher for adults ≥75 \nyears of age with versus without CKD , 4.2 times higher for adults with COPD, and about 2 to 3 \ntimes higher for adults with severe obesity, asthma, or CAD. \nRSV hospitalization rates were lowest among adults in the youngest age group of 50 ─64 years \nof age and were highest among adults in the oldest age group of ≥ 75 years of age. Although the \nabsolute rates clearly increased with age group, the adjusted rate ratios did not. Among adults \n≥50 years of age, RSV hospitalization rates were about 6.5 times higher for adults with CKD, \nabout 4.6 times higher for adults with COPD, around 3 times higher for adults with asthma or \nsevere obesity, and about 2 times higher for adults with CAD, diabetes, and current smokers. \nThe adjusted rate ratio for stroke and obesity were not statistically significant. \nAdults with 2 or more chronic conditions had the highest RSV hospitalization rates compared to \nthose with no chronic conditions. The adjusted rate ratios comparing the RSV hospitalization \nrate among those with 2 or more conditions to those with no conditions ranged from about 6.4 to \n12.4 depending on the age group. The adjusted rate ratios comparing RSV hospitalization rate \namong those with 1 condition to those with no conditions ranged from about 2.6 to 2.9 \ndepending on the age group. \nBased on these preliminary results, the conclusion was that select chronic medical conditions \nwere associated with greater rates of RSV -associated hospitalization among community -\ndwelling adults ≥50 years of age and varied by condition and age group. This information could \nhelp identify populations that might benefit most from RSV vaccines available to adults. \nDr. Carla Black (CDC/NCIRD) presented data on implementation of older adult RSV vaccines \nduring the 2023-2024 season.  Based on information from immunization information systems \n(IISs) submitted by jurisdictions to CDC through December 2023, coverage among adults ≥60 \nyears of age who had received ≥1 d ose RSV v accine varied by state and ranged from about 5% \nto about 18% among the 37 states reporting at that time. D ata are not available from all states, \nso these data are likely incomplete and probably are an underestimation of coverage. \nAccording to the National Immunization Survey, as of February 3, 2024, coverage among adults \n≥60 years of age was about 22.4%. Notably, the number who said they probably would get \nvaccinated or were unsure has remained consistent over time. Looking at coverage by demographics based on monthly data using a Kaplan-Meier estimation procedure using all data \ncollected since September and including coverage as of the end of December 2023, coverage was slightly lower. By age group, coverage was lowest in adults 60─64 years of age and \nhighest in all age groups ≥65 years of age. Coverage was highest among White adults at \n22.5% . Asian adults had similar coverage to White adults at 16.7%, but every other racial ethnic \ngroup had lower coverage compared to White adults. \n49 \n \n  \n   \n \n  \n   \n  \n \n       \n    \n  \n  \n  \n   \n  \n \n \n \n    \n  \n    \n  \n \n  \n    \n  \n  \n  \n  \n   \n  \n  \n \n \n \n  \n \n  \n   \n  \n    \n  \n   \n  \n  \n  \n   \n \n  For example, Black adults had about 10 percentage points lower coverage at 12.9% . Some \ngroups like NH/OPI had quite low coverage, which was 3.2%. \nAdults ≥60 years with 1 or more chronic conditions had significantly higher RSV vaccination \ncoverage of about 25% than those with no chronic conditions at about 18 %. Each individual \nchronic condition was elevated compared to people with no conditions, with the exception of \npeople with neurological conditions who had lower coverage compared to people with no conditions. Coverage decreased as the Social Vulnerability Index (SVI) of the county of \nresidence increased. Coverage was higher among people who received a n influenza vaccine for \nthe season or an updated COVID vaccine. Among people who received an influenza vaccine, \nRSV coverage was about 30.5% and among those who had an updated COVID vaccine, RSV \ncoverage was 38.5%. Coverage also varied by region. Coverage was lower among people \nresiding in rural areas compared to those in urban and suburban areas. Coverage increased \nwith increasing income and with increasing education. \nRegarding co-administration among adults ≥60 years of age, among those who received an \nRSV vaccine , 57.1% received RSV alone, about 20% received RSV and influenza together, \nabout 15% received 3 vaccines together (RSV, Influenza, COVID) , and 8.5% received RSV and \nCOVID vaccine s together. The most recent data show that 84.4% of people were vaccinated in \na pharmacy compared to about 14% who were vaccinated in medical settings (e.g., physician \noffices, hospitals, health departments , mass vaccination sites, and other medical settings ).  \nIQVIA data are based on medical claims from pharmacies and physicians practicing in medical offices. IQVIA uses a sample of claims from medical offices to project vaccinations given in all \nmedical offices in the US, which is based on a fairly small number of physicians. There is a lag \nwith the medical office data, which do not completely mature until about 2 months. The national \nretail pharmacy data are a projection based on a much larger percentage of all pharmacies in \nthe US. Claims from pharmacies come in much faster, so there is higher confidence in the \ncompleteness of the pharmacy data. None of the IQVIA data include vaccinations given in other medical settings such as public health clinics and hospitals, nor do they include vaccinations \ngiven in non -medical settings. Therefore, it is known that this is not a complete assessment of \nall RSV vaccines given in all settings in the US. \nIn terms of cumulative projected vaccines given to date in pharmacies and physician offices, a \ncombined total of 9.65 million RSV vaccinations were administered in retail pharmacies (9.36 \nmillion) and physician medical offices (291,599) as of February 3, 2024. An additional 164,254 \nRSV vaccinations were administered in long-term care pharmacies. Each week, the majority of \nvaccines were the GSK product at about 69% compared to 31% of the Pfizer product. In \npharmacies, vaccinations peaked in about late October to early November and have been \ndeclining since. Co-administration data from IQVIA showed similar patterns as in the NIS data \namong all people who received RSV vaccine and other vaccines that were given on the same \nday. About 52% received RSV only , about 22% received RSV and influenza vaccine, about 12% \nreceived RSV and COVID vaccine, and approximately 13.5% received RSV, influenza, and \nCOVID vaccines together. \nUsing data from both NIS and IQVIA , the estimated range of persons vaccinated was \napproximately 11– 18 million and estimated percent of persons vaccinated was 14%–22%. \n50 \n \n  \n \n     \n  \n \n   \n \n \n   \n  \n \n  \n  \n \n      \n \n \n \n    \n   \n  \n   \n   \n    \n    \n   \n   \n  \n    \n   \n  \n     \n \n  \n  \n  \n \n   \n \n    \n      \n  \n \n Transitioning to RSV v accination attitudes , data for this analysis were collected through the \nIPSOS KnowledgePanel and NORC AmeriSpeak Omnibus Surveys, which use probability -\nbased panels to survey a nationally representative sample of US adults ≥18 years of age. CDC \nfields questions about vaccination status, intent, knowledge, attitudes, beliefs, and behaviors on \neach survey for 2 waves each month, for a combined sample size of approximately 4,000 respondents. Data were weighted to represent the non-institu tionalized US population and \nmitigate possible non-response bias. All responses were self-reported. Among respondents who \nreported that they received or definitely would get the vaccine, 84% reported no concerns or \nissues. The top 3 reasons cited by those who expressed concerns were side effects (4.6%), not \nhaving enough knowledge about RSV or the vacci ne (2.6%), and not having time (2.5%). \nAmong those who said they probably would get the vaccine or were unsure, about 35% \nreported no concerns or issues. In this group, the top concerns cited were no HCP \nrecommendation (25.8%), do not know enough about RSV or the vaccine (23%), and the \nvaccine is too new (11.8%). Of respondents who said they probably or definitely would not get the vaccine, about 26% reported that they had no concerns or issues. The top 3 concerns cited \namong those who had concerns were not trusting the government or pharma (28.2%), not knowing enough about RSV or the vaccine (23%), and the vaccine is too new (21.2%). The most common concerns reported the previous day for COVID vaccines pertained to safety and \nside effects, while for RSV vaccine it was more about lack of information and lack of provider \nrecommendation. \nRegarding implementation considerations, there are a number of potential factors contributing to \nrelatively low vaccination coverage among people ≥60 years of age. As with any new vaccine, it \ntakes time to integrate into systems, gain wide access, increase awareness among HCP, and \nnormalize among the population. The 22% coverage seen for RSV vaccine is not out of line with \nwhat has been observed with other new vaccines within the first year of introduction. Because \nRSV is recommended based on shared clinical decision -making and the denominator for all of \nthese calculations was the population ≥60 years of age, not everybody ≥60 years of age is \nactually expected to be vaccinated because it is not a universal recommendation. There are \nseveral other issues with a shared clinical decision-making recommendation. There is feedback \nfrom HCP that that having these conversations is not simple in practice, and they are confusing \nfor providers and patients compared with routine universal recommendations. Also, vaccines \nare often administered by nurses, medical assistants , and pharmacists who are not always \ncomfortable with a shared clinical decision-making conversation or who do not feel like it is \nwithin their scope of practice. In addition, these provider types often give vaccines under \nstanding orders, which are difficult with shared clinical decision-making and may not be allowed \nin some states. People who do not have access to healthcare might not have a primary provider \nwith whom they can have a shared clinical decision-making discussion.  RSV vaccine is billed \nunder Medicare Part D unlike influenza and COVID vaccines, which results in billing issues in \nprovider offices. Vaccines are costly, meaning a costly upfront investment to carry the vaccine. \nHowever, referral to a pharmacy means that a patient may be less likely to be vaccinated. \nResidents of long-term care have additional, specific challenges. \nDr. Tom Shimabukuro (CDC/NCIRD) provided an update on CDC vaccine safety monitoring for \nRSV vaccines in adults ≥60 years of age. In the pre-licensure studies for Pfizer among 20,255 \nvaccine recipients ≥60 year of age, 2 cases of GBS were observed within 42 days of \nvaccination. In the pre-licensure studies for GSK among 18,304 recipients ≥60 years of age, 1 \ncase of GBS was observed within 42 days of vaccination. \n51 \n \n   \n \n   \n \n    \n    \n   \n    \n  \n  \n  \n  \n   \n \n     \n   \n    \n    \n   \n  \n   \n  \n  \n     \n   \n \n     \n       \n  \n   \n   \n   \n   \n     \n  \n   \n  \n   \n    \n \n \n   \n \n \n \n   \n Due to the small number of GBS cases and the size of the pre-licensure studies, it is not known \nat this time whether these GBS cases or other neuroinflammatory events occurred due to \nrandom chance or whether RSV vaccination might increase the risk of these events. Post-\nlicensure safety monitoring of RSV vaccines is ongoing. \nA new version of V -safe is now available that requires previous and new users to create an \naccount. It includes email and text messaging functionality. Including an email address is an \nadditional feature in this version of V -safe. Vaccines currently monitored include RSV vaccines \nfor older adults and pregnant persons and COVID vaccines for persons ≥6 months and older. V-\nsafe sends health surveys after vaccination daily during the first week and then weekly through \n6 weeks. The daily surveys solicit local and systemic reactions and health impacts. T here are \nadditional questions for persons who reported immunocompromising conditions at vaccination. The weekly surveys solicit new symptoms or conditions after vaccination. Participants reporting \nmedically -attended health impacts are encouraged to complete a VAERS report. \nIn terms of the demographic characteristics for adults ≥60 years of age who reported RSV \nvaccination from the early V-safe data, there were 15,745 registrants between October 20, \n2023─ January 28, 2024 . Respondents were predominantly of White race and most participants \nreported that their current state of health was excellent, very good, or good. Vaccines that were \ncommonly reported as co -administered with RSV vaccines were COVID -19 and influenza. \nReactions and health impacts reported for adults ≥60 years of age at least once during Day s \n0─7 following vaccination by manufacturer, injection site reactions and systemic reactions were \nfairly commonly reported. They were more commonly reported following the GSK vaccine in the \nfirst week following vaccination than the Pfizer vaccine. As a reminder, the GSK vaccine \ncontains an adjuvant. A small number of individuals reported receiving medical care, which was \nnot necessarily tied to a vaccine AE. \nVAERS is the nation’ s early warning system for vaccine safety. It is a spontaneous reporting or \npassive surveillance system that is co-managed by CDC and FDA. The strengths of VAERS are \nthat it can rapidly detect safety signals and can detect rare AEs. As a spontaneous reporting \nsystem, the main limitation of VAERS is that it is not designed to assess causality. VAERS \naccepts all reports from all reporters without making judgements on causality or judging the \nclinical seriousness of the event. As a hypothesis -generating system, VAERS identifies potential \nvaccine safety concerns that can be studied in more robust data systems. For all vaccines, \nsigns and symptoms of AEs are coded using the Medical Dictionary for Regulatory Activities \n(MedDRA) Preferred Terms (PTs). MedDRA PTs are not mutually exclusive, so a single report \nmay be assigned more than 1 MedDRA PT. Reports of SAEs were individually reviewed along \nwith accompanying medical records if available. Brighton Collaboration Case Definitions were \napplied for neuroinflammatory conditions, GBS, and ADEM. Reporting rate calculations used doses of vaccine administered for each type of RSV vaccine. Empirical Bayesian data mining \nwas conducted by FDA to detect disproportional reporting for the entire post-marketing period \nfor each product. \nA number of AESIs that are currently being monitored for RSV vaccination include death, \nGuillain -Barré syndrome, acute disseminated encephalomyelitis, transverse myelitis, chronic \ninflammatory demyelinating polyneuropathy, anaphylaxis, atrial fibrillation, other \nsupraventricular tachycardia, optic neuritis, multiple sclerosis, Bell’s palsy, \nencephalitis/encephalomyelitis, meningitis/meningoencephalitis, myelitis, vaccination errors, and adverse events following simultaneous administration with COVID -19, inactivated influenza, or \nother adult vaccines. \n52 \n \n   \n     \n         \n     \n     \n   \n \n    \n    \n  \n   \n   \n \n  \n  \n  \n     \n     \n   \n  \n   \n  \n   \n   \n \n   \n      \n    \n   \n \n  \n \n       \n    \n      \n   \n    \n   \n \n \n \n \n  \n \n      \n  \n   \n \n  As of February 16, 2024 , there were 3,689 total reports to VAERS after RSV vaccines, which \nwas after approximately 9.6 million doses administered. The total number of reports for the 2 \nproducts was 2,516 for GSK and 1,045 for Pfizer, which track s closely with the doses \nadministered. The median age, female proportion, and serious and non- serious proportions \nwere similar between the 2 vaccines and similar to what is seen with other vaccines \nadministered among adults ≥60 years of age. Looking at the most frequently reported MedDRA -\npreferred terms in adults ≥60 years of age broken down by manufacturer , for both the Pfizer and \nthe GSK vaccines, the most commonly reported symptoms were local and systemic reactions. \nThe safety profile for these most commonly reported symptoms for the 2 vaccines were similar . \nMedDRA -preferred terms of the reports by non-serious and serious status , non-serious reports \ndominated and was similar to local and systemic reactions. Some of the serious reports were \ngeneral conditions like asthenia, fatigue, gait disturbance, muscular weakness , and GBS. \nOn January 19, 2024, a data mining alert for disproportional reporting was detected in FDA ’s \nEmpirical Bayesian data mining for the Pfizer vaccine and GBS. No data mining alert for the GSK vaccine and GBS has been detected to date. Empirical Bayesian data mining is product-specific and analyzes product-specific VE event pairings compared to the overall VAERS \ndatabase. A total of 37 preliminary reports were received as of February 16, 2024. Of these, 6 \nare currently under review , 7 were excluded based on medical record review, and 1 was verified \nbut was excluded due to onset after 42 days. This left 23 verified GBS reports by medical record \nreview , of which 15 were after the Pfizer vaccine and 8 were after GSK vaccine. The median \nage in these reports was 71 years , with an interquartile range of 63─ 75 years of age. There was \n1 report in a non-pregnant female in her 50s who received Pfizer. T hat vaccine was either given \noff-label or in error. \nThe median time to onset was 9 days, with a range 1─ 22 days. There were 14 males and 9 \nfemales, none of whom were pregnant. There was 1 death in a male patient in his 70s who \nreceived the GSK vaccine. All 23 verified reports met Brighton Collaboration criteria for GBS \ncomprised of 3 Brighton Level 1, 12 Level 2, 8 Level 3. Brighton Level 1 is the highest level of \ndiagnostic certainty. Level 4 or 5 are not considered cases. Commonly administered vaccines \nwere COVID -19 vaccines and influenza vaccines. \nThe reporting rate in the 21-day risk window was 4.6 reports per million doses administered for \nthe Pfizer vaccine and 1.1 reports per million doses administered for the GSK vaccine. For the \n42-day risk window , the reporting rate was the same for Pfizer because all of those cases had \nonset within 21 days. There was 1 case with a 22-day onset. For the 42-day risk window, there \nwere 4.6 reports per million doses administered for the Pfizer vaccine and 1.2 reports per million \ndoses administered for the GSK vaccine. Putting the observed reporting rates into the context of \nwhat would be expected can be challenging with VAERS data passive surveillance. The chart-confirmed rate of GBS after mRNA COVID -19 vaccination in the VSD was used as a proxy for \nbackground rate. To be clear upfront, safety monitoring of the mRNA COVID-19 vaccines in \nVSD did not detect an increased risk of GBS associated with either of the mRNA COVID -19 \nvaccines. Therefore, the rate of GBS following mRNA COVID -19 vaccination can be used as a \nproxy for the background rate of GBS in a vaccine -accepting population. \nThis rate is appropriate because it is a relatively current rate within the past several years. This \nis primarily monovalent mRNA vaccination. All of these cases were a priori chart-reviewed during the normal process of VSD surveillance for mRNA COVID -19 vaccines. There are some \nlimitations with this method (e.g., different populations, different time periods, different age groups) . \n53 \n \n  \n   \n    \n \n   \n    \n   \n \n   \n  \n \n  \n  \n  \n  \n   \n \n  \n  \n   \n  \n \n   \n    \n \n \n       \n \n   \n     \n      \n    \n    \n   \n   \n      \n  \n \n   \n  \n   \n \n   \n   \n \n  \n    \n   \n  The estimated rate of GBS in adults ≥65 years of age following mRNA COVID-19 vaccines \nprimary series in VSD in the 21-day risk interval was 3.4 per 100,000 person years and in the \n42-day risk interval was 4.5 per 100,000 person years. Again, because the mRNA COVID -19 \nvaccines are not associated with an increased risk of GBS, this can be considered the \nbackground incidence of GBS in a vaccine-accepting population. When that is converted to per \nmillion doses in the 21-day risk interval, the expected cases per 1 million RSV doses \nadministered would be 2 cases per million doses administered with a range from the 95% \nconfidence interval of 0.7─ 4.2. For the 42-day risk interval, the expected cases per 1 million \nRSV doses administered would be 5.2 cases per million doses administered with a range from \nthe 95% confidence interval of 2.8─ 8.9. \nReturning to the observed VAERS reporting rates after RSV vaccination among adults ≥60 \nyears of age compared to the expected rate per million doses administered, in the 21 -day risk \ninterval for the Pfizer vaccine, the VAERS reporting rate was 4.6 per million doses administered and the expected rate based on VSD data would be 2 per million doses administered with the \nupper bound of the confidence interval at 4.2. That point estimate for the reporting rate was \nelevated for the Pfizer vaccine. For the GSK vaccine, reporting rates after RSV vaccination \namong adults ≥60 years of age compared to the expected rate per million doses administered in \nthe 21-day risk interval for the GSK vaccine was 1.1 per million doses administered compared \nto the expected rate of 2.0. That falls within the 95% confidence interval. For the 42-day risk \nwindow for the Pfizer for 4.6 per million doses administered, the estimated expected rate based \non VSD data would be 5.2 with a confidence interval of 2.8 ─8.9. For the GSK vaccine, it \nincreased to 1.2 per million doses administered because of the extra case at 22 days. The \nreporting rate was not elevated when compared to the background in VSD. The caveat is that \nthere is known to be underreporting in VAERS, so the observed VAERS reporting rates are \nlikely an underestimate of the true rate. \nThe VSD is CDC’s active surveillance system used for R apid Cycle Analysis (RCA) and \nresearch that was established in 1990. It has about 13.5 million individuals across the sites , \nincluding about 2.8 million adults ≥60 years of age. Looking at the observed VSD GBS rates \nfollowing RSV vaccination in adults ≥60 years of age through December 30, 2023, the VSD \nidentified 4 GBS cases within 1─ 84 days of receipt of the GSK vaccine. All 4 cases under went \nmedical record review and were adjudicated. The rates for the GSK vaccine were 9.5 per million \ndoses administered 21-day risk window and 14.3 per million doses administered in the 42-day \nrisk window. Qualitatively, these rates were higher than rates observed for high-dose influenza \nand Shingrix. The caveat is that these are very early data based on a small number of cases \nand a small number of doses administered. The 4\nth case was not included because it was \nclassified as Level 4 and is pending additional review. Currently, no cases of GBS have been \nobserved after the Pfizer vaccination, but only about 10% of all vaccinations in the VSD have \nbeen with Pfizer. The VSD will continue to monitor the safety of RSV vaccines in adults ≥60 \nyears of age . Formal sequential safety analys es will begin March 2024 using a vaccinated \nconcurrent comparison group, which is similar to what was done for COVID. \nTo summarize, local and systemic symptoms were the most commonly reported AEs following \neither of the RSV vaccines. Monitoring in VAERS indicated a higher -than-expected number of \nGBS reports following the Pfizer vaccine, but VAERS is subject to the limitations of passive \nsurveillance. GBS cases were observed in the pre -licensure clinical trials for both the Pfizer and \nthe GSK vaccines. GBS is included as an AE in the labels of both vaccines. Early data from \nVSD suggests a potential for an increased rate for GBS after the GSK vaccine, but additional \nanalys es are needed to further assess this potential risk. Insufficient doses of the Pfizer vaccine \nhave been used in VSD to inform risk. \n54 \n \n   \n  \n \n \n    \n   \n      \n    \n      \n \n    \n       \n   \n     \n     \n  \n      \n  \n \n    \n  \n \n     \n   \n    \n  \n \n  \n    \n     \n    \n     \n     \n \n \n…[truncated]", "summary": "MEETING OF THE ADVISORY  COMMITTEE ON IMMUNIZATION  PRACTICES (ACIP)  FEBRUARY 28-29, 2024  MEETING SUMMARY  Trade names are used for identification purposes only and do not indicate endorsement.                                                                                                                                                               WEDNESDAY: FEBRUARY 28, 2024  WELCOME AND INTRODUCTIONS  Call to Order/Roll Call  Dr. Melinda Wharton (ACIP Executive Secretary & Acting Chair ,…", "source_url": "https://www.cdc.gov/acip/meetings/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/minutes/summary-2024-02-28-29-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "minutes", "tags": ["acip", "cdc", "vaccines", "minutes"], "page_count": 100}
{"title": "agenda 2023 10 25 26 508", "content": "FINAL - October 23, 2023\n8:00 Welcome & Introductions Dr. Grace Lee (ACIP Chair)\nDr. Melinda Wharton (ACIP Executive Secretary, CDC)\n8:30 Meningococcal Vaccines\nIntroduction\nPlan for revisiting adolescent schedule for meningococcal vaccinesComparison of Pfizer and CDC cost effectiveness analysesSummary of EtR and proposed recommendations for Pfizer’s \nMenABCWY vaccine \nVaccines for Children ResolutionDr. Kathy Poehling (ACIP, WG Chair)\nDr. Lucy McNamara  (CDC/NCIRD)Dr. Ismael Ortega-Sanchez (CDC/NCIRD)Dr. Jennifer Collins (CDC/NCIRD)\nDr. Jeanne Santoli (CDC/NCIRD)\n10:10 Break\n10:25 Mpox Vaccines\nIntroduction\nUpdates about U.S. mpox epidemiology, vaccine safety, and vaccine \neffectiveness\nEvidence to recommendations framework\nReview of voting language and clinical guidanceVaccines for Children resolutionDr. Pablo Sanchez (ACIP, WG Chair)Dr. Faisal Minhaj (CDC/NCEZID)\nDr. Agam Rao (CDC/NCEZID)\nDr. Agam Rao (CDC/NCEZID)Dr. Jeanne Santoli (CDC/NCIRD)\n12:15 Break\n12:45 Public Comment\n1:00 VOTES\nMeningococcal Vote\nMeningococcal VFC VoteMpox VoteMpox VFC VoteDr. Jennifer Collins (CDC/NCIRD)Dr. Jeanne Santoli (CDC/NCIRD)Dr. Agam Rao (CDC/NCEZID)Dr. Jeanne Santoli (CDC/NCIRD)\n1:30 Break\n1:45 RSV - Adults\nIntroduction\nGSK safety and immunogenicity in persons 50-59 years of ageEpidemiology of RSV in adultsWork group interpretation and ACIP discussionDr. Camille Kotton (ACIP, WG Chair)Dr. Susan Gerber (GSK)Dr. Monica Patton (CDC/NCIRD)Dr. Amadea Britton (CDC/NCIRD)\n3:00 Influenza Vaccines\nIntroduction\nSafety of quadrivalent recombinant influenza vaccine in pregnant \nwomen and their infants\nPregnancy outcomes with ccIIV4 (Flucelvax): results of a post-\nmarketing study\nSafety of simultaneous versus sequential administration of mRNA \nCOVID-19 and Quadrivalent Inactivated Influenza (IIV4) Vaccines: \nA randomized placebo controlled trial\nSafety of simultaneous vaccination with Zoster Vaccine Recombinant \n(RZV) and quadrivalent Adjuvanted Inactivated Influenza Vaccine \n(allV4)Dr. Jamie Loehr (ACIP, WG Chair)\nDr. Nicky Klein (Kaiser Permanente Northern California)\nDr. Gregg Sylvester (Seqirus)\nDr. Chip Walter (Duke University)\nDr. Ken Schmader (Duke University)\n4:30 Vaccine Safety Update\nUpdate on COVID-19 and Influenza Vaccine Safety Dr. Tom Shimabukuro (CDC/NCEZID)\n5:30 AdjournMEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)\nCenters for Disease Control and Prevention\nAtlanta, Georgia 30329  \nOctober 25-26, 2023\nWednesday, October 25, 2023\nFINAL - October 23, 2023\n8:00 Welcome & Introductions Dr. Grace Lee (ACIP Chair)\nDr. Melinda Wharton (ACIP Executive Secretary, CDC)\n8:10 Agency Updates\n8:30 Combined Immunization Schedules\nIntroduction to 2024 adult and child/adolescent immunization \nschedule\n2024 child and adolescent schedule revisions     \n2024 adult schedule revisions                                               Dr. Sybil Cineas (ACIP, WG Chair)\nDr. Patricia Wodi (CDC/NCIRD)\nDr. Neil Murthy (CDC/NCIRD)\n9:50 Break\n10:00 Public Comment\n10:15 VOTES\nImmunization Schedules Vote Dr. Patricia Wodi (CDC/NCIRD), Dr. Neil Murthy \n(CDC/NCIRD)\n10:30 Chikungunya Vaccine\nIntroduction\nEtR and proposed policy options for chikungunya vaccine use among \nU.S. adults traveling abroad \nEtR and proposed policy options for chikungunya vaccine use among \nlaboratory workersDr. Beth Bell (ACIP, WG Chair)\nDr. Susan Hills (CDC/NCEZID)\nDr. Susan Hills (CDC/NCEZID)\n11:40 Dengue Vaccines\nTakeda dengue vaccine update Dr. Wilbur Chen (ACIP, WG Chair)\n11:45 Break\n12:00 COVID-19 Vaccines\nIntroduction\nCOVID-19 vaccine implementationCOVID-19 vaccine policy and next steps Dr. Matt Daley (ACIP, WG Chair)Dr. Shannon Stokley (CDC/NCIRD)Dr. Megan Wallace (CDC/NCIRD)\n12:50 Pneumococcal Vaccines\nWork Group Updates and Next Steps Dr. Miwako Kobayashi (CDC/NCIRD)\n1:00 Influenza Vaccines\nEffectiveness of maternal influenza vaccination during pregnancy \nagainst influenza-associated hospitalizations & emergency departmevisits in infants <6 Months of Age\nUpdate on influenza B/Yamagata surveillancen\nt Ms. Samantha Olson (CDC/NCIRD)\nDr. Rebecca Kondor (CDC/NCIRD)\n1:40 Adjourn\nAcronyms\nCDC\nCMS Centers for Medicare and Medicaid Services \nCOVID-19 Coronavirus disease 2019\nEtR Evidence to Recommendations Framework\nFDA Food and Drug Administration\nGRADE\nHRSA Health Resources and Services Administration\nIHS Indian Health Service\nLAIV4 Live Attenuated Influenza Vaccine\nNCHHSTP\nNCIRD\nNCEZID\nNIAID\nOIDP Office of Infectious Disease and HIV/AIDS Policy\nSARS-CoV-2 Severe Acute Respiratory Syndrome Coronavirus 2\nWG Work Group\nWHO World Health Organization\nVE Vaccine EffectivenessNational Institute of Allergy and Infectious DiseasesCenters for Disease Control and Prevention\nGrading of Recommendations Assessment, Development and Evaluation\nNational Center for HIV, Hepatitis, STD and TB Prevention [of CDC/OID] \nNational Center for Immunization & Respiratory Diseases [of CDC/OID] \nNational Center for Emerging and Zoonotic Diseases [of CDC/OID]Thursday, October 26, 2023", "summary": "FINAL - October 23, 2023 8:00 Welcome & Introductions Dr. Grace Lee (ACIP Chair) Dr. Melinda Wharton (ACIP Executive Secretary, CDC) 8:30 Meningococcal Vaccines Introduction Plan for revisiting adolescent schedule for meningococcal vaccinesComparison of Pfizer and CDC cost effectiveness analysesSummary of EtR and proposed recommendations for Pfizer’s  MenABCWY vaccine  Vaccines for Children ResolutionDr. Kathy Poehling (ACIP, WG Chair) Dr. Lucy McNamara  (CDC/NCIRD)Dr. Ismael Ortega-Sanchez…", "source_url": "https://www.cdc.gov/acip/meetings/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/agendas/agenda-2023-10-25-26-508.pdf", "doc_date": "2023-10-25", "case": "acip", "sub_case": "agendas", "tags": ["acip", "cdc", "vaccines", "agendas"], "page_count": 2}
{"title": "summary 2023 10 25 26 508", "content": "MEETING OF THE ADVISORY \nCOMMITTEE ON IMMUNIZATION \nPRACTICES (ACIP) \nOCTOBER 25 -26, 2023 \nMEETING SUMMARY \nCONTENTS  \nWEDNESDAY: OCTOBER 25, 2023 .............................................................................. 4 \nSafety of Quadrivalent Recombinant Influenza Vaccine in Pregnant Women and Their \nSafety of Simultaneous versus Sequential Administration of mRNA COVID -19 and  \nQuadrivalent Inactivated Influenza (IIV4) Vaccines: A Randomized Placebo Controlled Trial Safety of Simultaneous Vaccination with Zoster Vaccine Recombinant (RZV) and WELCOME AND INTRODUCTIONS ................................................................. 4 \nMENINGOCOCCAL VACCINES ...................................................................... 4 \nIntroduction ............................................................................................................................ 4 \nPlan for Revisiting Adolescent Schedule for Meningococcal Vaccines ................................. 5 \nComparison of Pfizer and CDC Cost -Effectiveness Analyses ............................................... 8 \nPfizer Statement .................................................................................................................. 16 \nSummary of EtR and Proposed Recommendations for Pfizer’s MenABCWY Vaccine .......17 \nVaccines for Children (VFC) Resolution .............................................................................. 30 \nVote: Meningococcal Vaccine .............................................................................................. 31 \nVote: Meningococcal VFC Resolution ................................................................................. 32 \nMPOX VACCINES ........................................................................................ 33 \nIntroduction .......................................................................................................................... 33 \nUpdates about US Mpox Epidemiology, Vaccine Safety, and Vaccine Effectiveness ......... 35 \nEtR Framework for the JYNNEOS Vaccine ......................................................................... 40 \nReview of Voting Language and Clinical Guidance ............................................................. 50 \nVote: Mpox Vaccine Recommendation ................................................................................ 53 \nVote: VFC Mpox Resolution ................................................................................................ 54 \nADULT RESPIRATORY SYNCYTIAL VIRUS (RSV) VACCINES ....................... 55 \nIntroduction ........................................................................................................................ 55 \nINFLUENZA VACCINES ............................................................................... 73 \nIntroduction .......................................................................................................................... 73 \nInfants .................................................................................................................................. 74 \n............................................................................................................................................. 77 \nQuadrivalent Adjuvanted Inactivated Influenza Vaccine (allV4) .......................................... 81 \n1 \n \n   \n   \n    \n    \n   \n   \n   \n   \n   \n   \n   \n   \n   \n   \n   \n   \n    \n   \n   \n   \n   \n   \n   \n   \n   \n \n   \n \n   \n   \n   \n   \n   \n   \n   \n   Effectiveness of Maternal Influenza Vaccination during Pregnancy against Influenza-\nAssociated Hospitalizations & Emergency Department Visits in Infants <6 Months of Age 84 \nUpdate on Influenza B/Yamagata Surveillance ................................................................... 87 \nPost Marketing Study: Pregnancy Outcomes with ccIIV4 (Flucelvax) ................................. 90 \nUPDATE ON COVID -19 AND INFLUENZA VACCINE SAFETY ........................ 92 \nIntroduction ........................................................................................................................ 92 \nPUBLIC COMMENTS ................................................................................... 98 \nOverview .............................................................................................................................. 98 \nPublic Comments ................................................................................................................. 98 \nTHURSDAY: OCTOBER 26, 2023 ............................................................................. 103 \nAGENCY UPDATES .................................................................................... 103 \nCenters for Disease Control and Prevention ..................................................................... 103 \nCenters for Medicare and Medicaid Services .................................................................... 105 \nFood and Drug Administration ........................................................................................... 106 \nHealth Resources and Services Administration ................................................................. 106 \nIndian Health Services ....................................................................................................... 107 \nNational Institutes of Health ............................................................................................... 107 \nOffice of Infectious Disease and HIV/AIDS Policy ............................................................. 108 \nSanofi Statement ............................................................................................................... 109 \nCOMBINED IMMUNIZATION SCHEDULE ..................................................... 110 \nIntroduction ........................................................................................................................ 110 \n2024 Child and Adolescent Schedule Revisions ............................................................... 111 \n2024 Adult Schedule Revisions ......................................................................................... 118 \nVote: Immunization Schedules .......................................................................................... 123 \nCHIKUNGUNYA VACCINE .......................................................................... 123 \nIntroduction ........................................................................................................................ 123 \nEtR and Proposed Policy Options for Chikungunya Vaccine Use Among US Adults Traveling Abroad ............................................................................................................... 124 \nEtR and Proposed Policy Options for Chikungunya Vaccine use Among Laboratory Workers ............................................................................................................................. 132 \nDENGUE VACCINE .................................................................................... 135 \nCOVID -19 VACCINES ................................................................................. 137 \nIntroduction ........................................................................................................................ 137 \nImplementation Update on 2023– 2024 COVID -19 Vaccines ............................................ 137 \nCOVID -19 Vaccine Policy and Next Steps ........................................................................ 141 \nPNEUMOCOCCAL VACCINES ..................................................................... 146 \nPUBLIC COMMENTS .................................................................................. 149 \n2 \n \n    \n   \n  \n   \n   \n   \n \n  Overview ............................................................................................................................ 149 \nPublic Comments ............................................................................................................... 150 \nCERTIFICATION ......................................................................................................... 154 \nACIP MEMBERSHIP ROSTER .................................................................................. 155 \nACRONYMS USED IN THIS DOCUMENT ................................................................. 164 \nWRITTEN AGENCY UPDATES SUBMITTED ............................................................ 169 \n3 \n \n  \n \n \n \n  \n    \n  \n   \n \n \n   \n \n \n  \n \n  \n \n   \n \n \n \n \n  \n    \n \n  \n  \n   \n \n  \n \n \n  \n \n  \n \n  \n \n \n WEDNESDAY: OCTOBER 25,  2023  \nWELCOME AND INTRODUCTIONS \nDr. Grace Lee (ACIP Chair) called to order and presided over the October 25-26, 2023 \nAdvisory Committee on Immunization Practices (ACIP) meeting. She co nducted a roll call each \nday, which established that a quorum was present. A list of Members, Ex Officios , and Liaison \nRepresentatives is included in the appendixes at the end of this summary document. No \nconflict s of interest (COIs) were identified during this meeting and quorum was maintained \nthroughout both days. \nDr. Melinda Wharton (ACIP Executive Secretary, CDC) noted that copies of the slides for the \nmeeting were available on the ACIP website and were made available through a ShareLink ™ \nfile for ACIP Voting, Ex Officios , and Liaisons Members. She provided housekeeping \ninstructions and explained that the ACIP is, at its heart, a public body. Engagement with the \npublic and transparency in all of its processes are vital to the committee’s work. She indicated that there would be 2 oral public comment sessions during this meeting, which were scheduled \nfor approximately 12:50 PM Eastern Time ( ET) on October 25, 2023 and at approximately 10:00 \nAM on October 26, 2023. To create a fair and more efficient process, individuals interested in \nmaking an oral comment were asked to submit a request online in advance of the meeting. \nPriority is given to advance requests. If more people make requests than can be accommodated in the allotted time, speakers are selected through a blind lottery. The 14 speakers selected by lottery for this meeting were notified in advance of the meeting. Members of the public also had \nthe opportunity to submit written comments on issues coming before the ACIP via \nhttps://www.regulations.gov using Docket Number ID CDC-2023-0 079. More information on the \nwritten public comment process can be found on the ACIP website. \nAs noted in the ACIP Policies and Procedures manual , ACIP members agree to forgo \nparticipation in certain activities related to vaccines during their tenure on the committee. For \ncertain other interests that potentially enhance a member’s expertise while serving on the committee, CDC may issue limited COI waivers. Members who conduct vaccine clinical trials or \nserve on data safety monitoring boards (DSMBs) may present to the committee on matters \nrelated to those vaccines, but those members are prohibited from participating in committee \nvotes on issues related to those vaccines. Regarding other vaccines of the concerned company, \na member may participate in discussions with the provision that he/she abstains on all votes related to that company. ACIP members state any COIs at the beginning of each day of each \nmeeting. \nMENINGOCOCCAL VACCINES \nIntroduction \nKatherine Poehling, MD, MPH (ACIP, WG Chair) introduced the Meningococcal Vaccine Work \nGroup (WG). She reminded everyone of the 3 policy topics under consideration by the WG \n(pertaining to the Pfizer pentavalent vaccine): \n1. Should pentavalent vaccine be included as an option for MenACWY/MenB vaccination in \npeople currently recommended to receive both vaccines ? \n4 \n \n  \n \n \n \n \n \n \n  \n  \n   \n   \n   \n \n  \n   \n   \n   \n  \n      \n   \n  \n \n \n  \n \n \n  \n \n  \n  \n     \n \n \n   \n   \n \n \n \n \n \n   \n   \n    \n \n    \n   \n  \n   \n  \n    2. Should pentavalent vaccine be included as an option for people currently recommended to \nreceive MenACWY only ? \n3. Should pentavalent vaccine be included as an option for people currently recommended to \nreceive MenB only ? \nIn February 2023, the WG discussed the epidemiology of meningococcal disease in the United \nStates (US), Pfizer ’s MenABCWY vaccine clinical trials data, and the WG’s interpretation of \nthose data. In June 2023, the WG introduced the CDC ’s cost -effectiveness model and provided \na summary of the Grading of Recommendation s Assessment, Development, and Evaluation \n(GRADE ) and Evidence to Recommendation (EtR) Framework. \nBetween June and October 2023, the WG received feedback during the June ACIP meeting. A \nreview of the meningococcal schedule has been postponed to allow for consideration of GSK’s \nforthcoming pentavalent vaccine and availability of data about post-COVID meningococcal \nepidemiology. The WG also reviewed comparisons of the cost-effectiveness models. The CDC \ncost-effectiveness model has been updated with new price estimates. The price for pentavalent \nvaccine was $40 to $90 more than MenB but is now similar , so there has been an adjustment. \nThe WG also discussed 3 potential recommendation options based on the concerns raised by \nACIP members in June and the new cost-effectiveness assessments. \nTo summarize where the WG is, there is strong consensus among the WG members for the first \npolicy question regarding whether pentavalent vaccine should be included as an option for \nMenACWY/MenB vaccination in people currently recommended to receive both vaccines, which pertains to persons 16 to 18 years of age; it typically happens around 16 years. There was strong consensus among the WG members regarding the second policy question that the pentavalent vaccine should not be included as an option for people currently recommended to \nreceive the quadrivalent vaccine only, which pertains to the 7\nth grade dose. There was limited \nconsensus among WG members about the third question that perhaps pentavalent vaccine should be included as an option for people currently recommended to receive MenB only . This \nis the dose that typically is given just before college entrance or military service. \nDuring this session, presentations were provided on the plan for revisiting the adolescent schedule for meningococcal vaccines, a comparison of the Pfizer and CDC cost-effectiveness \nanalyses for Pfizer’ s MenABCWY vaccine , a summary of the EtR Framework and proposed \nrecommendations for Pfizer’ s MenABCWY vaccine, and a vote and the Vaccines for Children \n(VFC) Resolution. \nPlan for Revisiting Adolescent Schedule for Meningococcal Vaccines \nLucy McNamara, PhD, MS (CDC/NCIRD) provided a brief update on the meningococcal \nvaccine WG’s plans for revisiting the adolescent schedule for meningococcal vaccines over the \nnext year. As mentioned earlier, a great deal of interest was expressed during the June 2023 \nACIP meeting in revisiting the current meningococcal vaccine schedule for adolescents. Some \nof the questions that were raised regarded whether the dose of MenACWY at 11 to 12 years of \nage is still needed, especially given recent epidemiology of very low disease burden among \nthose 11─ 15 years of age. There also were some questions around the shared clinical decision-\nmaking recommendation for B vaccines. It was noted that the availability of pentaval ent \nmeningococcal vaccines may complicate the shared clinical decision-making discussion for \nproviders and that some nuances , such as the projected short duration of serogroup B \n5 \n \n      \n  \n  \n    \n    \n \n   \n   \n \n      \n  \n   \n  \n  \n   \n   \n  \n  \n  \n \n  \n \n \n  \n \n   \n \n \n  \n \n \n \n   \n \n \n  \n    \n   \n    \n \n    \n   \n  \n     \n   \n    \n   \n    protection may be lost, when it is possible to give a single injection covering all 5 serogroups. It \nalso was highlighted that opportunities to reduce the total number of vaccines given, by \nleveraging pentavalent vaccines for instance, would be appealing if it is possible to still maintain \na high level of protection. The WG considered this feedback and decided to incorporate \nrevisiting the adolescent schedule into its work plan over about the next 15 months. \nThere are a number of reasons that the WG is planning to spread this evaluation out over that timeframe rather than trying to push to accomplish it more quickly. The WG would like to ensure \nthat there is adequate time to complete and fully evaluate the necessary GRADE and EtR assessments, including addressing questions about cost-effectiveness and the importance of \nthe booster response for what currently is the second dose of MenACWY vaccines for \nprotecting older adolescents. The WG anticipates being able to assess the extended interval \ndata for pentavalent vaccines administered more than a year apart at some point during 2024, \nwhich will open new options for spacing of meningococcal vaccine doses. The WG wants to \nmake sure that there is plenty of time to integrate the recommended changes into the overall \nChild and Adolescent Immunization Schedule in a way that will be clear to clinicians. In addition, \nthe WG wants to ensure that they can fully consider an additional year of post-COVID \nepidemiology, which they feel is particularly important in light of the new meningococcal strains \nin the US that are primarily affecting Black and Hispanic populations and have substantial \nimplications for health equity. \nWhile there are many ways the adolescent schedule for meningococcal vaccines could be \naltered, the WG plans to focus on the following core questions based on the input from the last \nACIP meeting: \n1. Should the MenACWY series recommendations be changed to begin at an older age than \ncurrently recommended at 11─12 years of age, to eliminate the dose recommended at \n11─12 years of age of MenACWY entirely, or to revise the recommendation to shared \nclinical decision-making? \n2. Should the MenB series recommendations be changed to alter the recommended ages or dosing interval to provide better protection for individuals 18─19 years of age, or should the shared clinical decision- making recommendation be revisited for some or all \nadolescents(e.g., those planning to attend college)? \n3. Are there ways to better integrate the MenACWY and MenB vaccine schedules to streamline administration and increase feasibility for providers ? \nThe WG established a tentative timeline for addressing these questions over the next 4 ACIP \nmeetings. In February 2024, the plan is to return to the committee, recognizing that there may \nbe a number of new members at that time, with more detailed terms of reference (TORs) for \naddressing the schedule change. In June 2024, the WG hopes to present epidemiologic \nanalysis that are relevant to possible schedule changes, including understanding the burden of \ndisease currently averted by the MenACWY dose at 11─ 12 years of age; assessment of racial \nand ethnic differences in disease burden among adolescents ; an analysis of the risk factors for \nserogroup B meningococcal disease among college versus non-college students ; an update on \nbreakthrough meningococcal disease cases in vaccinated individuals to inform the thinking \naround duration of protection of the vaccines ; and tentatively extended interval data for \nadministering 2 doses of pentavalent vaccines several years apart if they are available by that \npoint. In October 2024, the WG plans to cover the GRADE and EtR assessments for proposed \nchanges to the adolescent schedule and a cost -effectiveness analysis for changes to the \n6 \n \n    \n    \n \n  \n   \n \n \n \n  \n \n \n \n \n  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n   \n \n \n  \n  \n \n \n \n \n MenACWY and MenB adolescent schedules . The WG hopes to have votes during February \n2025. In addition, the WG also anticipates addressing upcoming policy questions related to an \nadditional pentavalent vaccine for which there is not yet a set timeline. The hope is to remain \nsomewhat flexible to ensure that the WG can appropriately integrate, review, and discuss the \nadditional pentavalent vaccine within the broader schedule change discussion. \nDiscussion Points \nDr. Daley inquired as to whether there is an ability to assess competing priorities. The \nincreasing complexity of the schedule can have negative side effects, such as challenges for providers in terms of knowing what to stock. For instance, a family medicine practice will be immunizing birth to older ages. Consideration will have to be given to number of products to stock, whether switches can be made from one product to another, how decisions will be made \nabout who should be vaccinated in an environment with clinical decision support versus one \nwithout, whether larger refrigerators will be needed to stock the various vaccine products, et cetera. There could be benefits to simplification that would then translate to other vaccine-preventable diseases. \nTo Dr. McNamara , this would fall under the “feasibility” component of the EtR Framework and \ndefinitely could be considered in the WG deliberations. She invited suggestions and resources \nfor data or evidence relevant to any proposed strategies in terms of how changes in t he \nmeningococcal vaccine schedule could affect overall feasibility in the clinical setting. \nDr. Talbot said she felt like they were doing this out of order. It seemed peculiar to vote for a \nnew vaccine, re-evaluate this in a few months, change the schedule, and then vote again. If \nthey wait to re-evaluate the vaccine, when to administer it, how much is needed, et cetera, the decisions would be clearer and less complicated for primary vaccinators. It will not help vaccination rates to make a decision during this meeting only to change it in 3 months. She suggested not voting on this vaccine until they know what schedule will be recommended. \nGiven that there currently are vaccines to cover these pathogens, there is no hurry to do this. \nThis differs from the hurry during COVID when people were dying and hospitals did not have enough staff, rooms, and ventilators. Therefore, she did not see the hurry for voting during this session. \nDr. McNamara agreed with this point and explained that this is a big part of why the WG framed \nthe PICO questions the way they did for the pentavalent vaccine. The intent pertained to \nwhether the pentavalent vaccine could be swapped in basically as a part of the exist ing \nrecommendations, not to change any of the existing recommendations for ACWY or B vaccines. At this juncture, the point is to let people know whether they can use the pentavalent vaccine in lieu of already recommended doses. The pentavalent vaccine was recently licensed and \ntypically, ACIP evaluates vaccines after they are licensed. She deferred to the ACIP Secretariat to discuss whether there truly is a hurry. The vaccine was licensed last week. \nDr. Wharton indicated that it would be up to ACIP about whether there would be a vote. A \nmotion and second would have to be made in order to move forward on a vote. As Dr. McNamara commented, the intent of this proposal was to provide a recommendation for use of \na licensed vaccine in the context of the current schedule upon which ACIP would vote the next \nday. A potential change in the current recommendations would clearly be a longer conversation. In the meantime, an ACIP vote would allow providers to use this recently licensed product within the context of the current schedule. \n7 \n \n    \n \n \n \n \n  \n  \n \n \n \n \n \n   \n     \n  \n \n \n  \n  \n \n   \n \n   \n   \n       \n \n \n \n     \n   \n  \n  \n \n \n \n  \n   \n    \n   \n     \n   \n  \n  Ms. Arthur (BIO) reminded the committee that because of the 21st Century Cures Act (Cures \nAct) that was passed a few years ago, there is a statutory obligation that newly licensed \nvaccines be evaluated and voted upon relatively close to their licensure at the nearest ACIP \nmeeting. \nDr. Kimberlin (AAP Redbook) said that in his personal view, he thought it was good that the WG \nwould be evaluating the meningococcal schedule over the next 18 months. He thinks it is always good to look for ways that things that have evolved over many years could be \nstreamlined and perhaps improved upon based upon current data. His recommendation would \nbe to try to avoid shared clinical decision-making recommendations. Increasingly, he is hearing from providers in the field that these do not really help. If, after 18 months, the WG cannot make a decision, it is unclear how a private practice pediatrician is supposed to do the same with much less information and much less time to do the deep dive than the expert ACIP members \nwere able to do. \nMs. Howell (AIM) acknowledged that while the ACIP does not determine immunization \nrequirements for school s, many states have 7\nth grade requirements or requirements around \nmeningococcal vaccine for children 11─12 years of age. If this change is made, states probably \nwould have to change legislation or rules. She expressed her hope that the WG would take this \ninto consideration. \nDr. Long agreed with Dr. Talbot that it would be difficult for the ACIP to talk about the current \nvaccine , because everything would be flavored by what they think about the schedule and the \nuse of meningococcal vaccines. Perhaps they should table this discussion until at least they \nhear the cost-effectiveness data because that may alter what they want to do. \nDr. Poehling emphasized that the WG has really spent a lot of time thinking about what the most \ncogent and efficient way to move forward would be. The question regards whether they have all \nof the information they need or would like. She said she would like to make the argument that they had enough information to make a decision during this meeting and that with the FDA ’s \napproval of this vaccine, no recommendation would mean that people would have to make \ndecisions with no guidance. In her opinion, it would be better to have ACIP guidance. \nDr. Fryhofer (AMA) noted that her comment was triggered by Dr. Daley ’s comment about \ncompeting priorities, complexity, and storage challenges. As increasingly more vaccines are \nrecommended, she encouraged pharmaceutical companies to make small quantities of \nvaccines available for purchase rather than making a minimum of tens, hundreds, or thousands \nof doses. That would increase access to vaccination. \nComparison of Pfizer and CDC Cost -Effectiveness Analyses \nIsmael R. Ortega-Sanchez, PhD (Senior Health Economist, CDC/NCIRD) discussed the \neconomics of the potential pentavalent meningococcal conjugate vaccine, comparing and \nsummarizing key elements and findings of 2 economic models (Pfizer and CDC) on the use of \npentavalent vaccine for the prevention of invasive meningococcal disease (IMD) among US \nadolescents. In the previous 8 to 9 months, the 2 models were updated several times. They also \nwere discussed extensively with the ACIP Meningococcal WG. For full disc losure, Dr. Ortega-\nSanchez indicated that he led the team conducting the CDC model. \n8 \n \n   \n \n  \n \n \n  \n \n \n  \n \n \n      \n   \n \n   \n   \n   \n  \n \n \n \n \n \n  \n   \n  \n  \n \n The 3 policy questions centered on analysis by both models are listed here: \n1. Should the pentavalent vaccine (MenABCWY) be considered as an option for \nMenACWY/MenB vaccination in people currently recommended to receive both vaccines? (PICO 1) \n2. Should the pentavalent vaccine (MenABCWY) be included as an option for people currently recommended to receive MenACWY only? (PICO 2) \n3. Should the pentavalent vaccine (MenABCWY) be included as an option for people currently recommended to receive MenB only? (PICO 3) \nIn general, the goal is to answer whether the new pentavalent vaccine should be considered as \nan option for the quadrivalent and MenB vaccination in people currently recommended to receive both vaccines. The starting point of the 2 economic models are the policy questions \nregarding potential recommendations for the use of pentavalent vaccine in adolescents. To consider the economic s of each policy question is to consider simultaneously the health benefits \nand cost of vaccination by answering the question, “Is vaccinating adolescents with the \npentavalent (MenABCWY) vaccine series to prevent invasive meningococcal disease in \nadolescents cost-effective relative to the use of quadrivalent and MenB vaccines?” To address \nthis question, the 2 models used the same comparator (e.g., the current standard of care). The \ncurrent standard of care and the hypothetical vaccines and vaccination strategies (interventions) in the model are labeled using the initials of the vaccine and serogroups contained in the dose, which are as follows:  \nTo have a visual about the comparisons of the Pfizer and CDC incremental analysis included in \nthe 2 models being compared, the table below describe the alignment of this incremental cost-\neffective analysis with the policy questions to be answered. An important and recurring detail in \nthis presentation is the price of a dose of pentavalent used as input in the specific incremental analysis : \n9 \n \n  \n \n \n    \n   \n    \n  \n   \n     \n  \n   \n \n  \n  \n   \n  \n   \n  \n \n \n \n  \n  \n  \n \nThe policy questions have important implications for the 3 groups of elements included in the \nmodels. The comparison of the 2 economic models focus es on how appropriate the selection of \nthe modeling approach is, the inputs, and the assumptions —especially those that are strong \ninfluential assumptions. In general, the 2 models follow similar designs with the use of a static \nanalytical decision-making approach, reliance on probabilistic or deterministic sensitivity \nanalysis to manage the various data uncertainties, a hypothetical cohort of adolescents ≥ 11 \nyears of age in the US, a timeframe of the first 15 years after 11 years of age to account for the \nvaccination schedules , loss of income associated with temporary productivity loss and \npremature mortality associated with meningococcal disease. \nOnce the modeling strategies were set, the 2 models were fed with different types of input data \n(e.g., epidemiologic, vaccine characteristics, healthcare resource utilization (HCRU) and cost, \nindirect cost quality of life, and other parameters). Across models, the sources, specific values, \nand assumptions of the parameters have some overlaps, but they were marked as different as well. In the boxes are the standard outcomes estimated and reported by the 2 models , though \nthe presentation focused primarily on the cost per quality -adjusted life year (QALY ) saved or the \nincremental cost-effectiveness ratio (ICER): \nSelected inputs for this comparison focused on the cost of the vaccine and vaccine administration, IMD incidence for the pre-vaccine and in vaccine era, initial vaccine \neffectiveness (VE) and waning over time, IMD-associated permanent sequalae, age and \nserogroup-specific Case Fatality Rate (CFR), and acute IMD QALY scores and unitary direct \ncosts . \n10 \n \n  \n   \n  \n  \n      \n   \n      \n   \n  \n  \n \n   \n   \n  \n \n    \n    \n    \n \n  \n   \n     \n \n  \n    \n    \n \n \n \n    \n \n   \n  \n      \n \n     \n   \n     \n   \n    \n      \n   \n  \n    \n \n    \n   \n \n  From March 2023 to June 2023, Pfizer submitted various technical reports using the \npentavalent vaccine price of $240 with a range of $230 to $250 per dose. In August 2023, Pfizer \nsubmitted a new technical report updating the pentavalent price to $250 for the private cost per dose and $187.50 for the public price . In October 2023, Pfizer submitted a newer technical \nreport updating the pentavalent prices for the strategies using 2 doses for pentavalent of $210 \nfor the private sector and $157.50 for the public sector. For the strategies with a single dose of \npentavalent, the price remained at $250. This distinction is very important in terms of analyzing \nthe specific outcomes estimated in each of the models. Regarding the various components of the vaccination program beyond the price per dose, v accine costs were differentiated based on \nthe 2023 public and private sector prices and vaccine administration settings for vaccines already available in the vaccination schedule. Ranges were estimated from public and pri vate \nvaccine prices and the cost of administration by site. Pentavalent was calculated using the \nhypothetical range of prices as released by Pfizer for the pentavalent vaccine in August and in \nOctober 2023. Although not included in these costs, in the CDC model, rates of moderate and severe adverse events (AEs) were taken into account using publications in the literature. Only \nthe CDC model considers vaccine wastage for open vial, mishandling, or outdated shelf life. \nAnother significant component in the total estimation is vaccination program costs. \nIn terms of the average annual incidence in v accine serogroups BCYW by age per 100,000 \nused in the models based on ABC Core Surveillance and the National Notifiable Diseases Surveillance System (NNDSS), rates of IMD remained relatively higher in late adolescents. But \nin general, rates have been declining for all ages. Overall, the incidence rates are 1/6 of those from the recent pre-vaccine era. In terms of the marked differences in the models, the CDC \nmodel used age by year IMD incidence data showing the peak in the late adolescent years, \nwhile the Pfizer model used only 4-year averages. Moreover, Pfizer extrapolated the average \nrates from late adolescents to the early 20s. This approach may underestimate the incidence in 10 years and overestimate the incidence in early 20 years. \nThe initial VE by vaccine dose and serogroup are critical data inputs to assess the vaccination \nimpact of the strategies. Value and assumptions on initial protection are based on value \nsources.\n1 The pentavalent is based on the Phase 3 noninferiority initial VE by a single dose at \n11 to 12 years of age and a second dose at 16 years of age of pentavalent vaccine as reported \nby Pfizer. For quadrivalent and MenB, the initial VE was based on effectiveness surveillance. \nOne of the key assumptions following initial VE was related to the duration of protection. This \nassumption was differentiated by serogroups containing the vaccine. Assumptions on vaccine \nprotection were more conservative in the CDC model. There was a fast decline in waning of \nvaccine protection in the CDC model for both the quadrivalent and MenB vaccines. For the \nPfizer model, there was an assumption based on vaccine protection as being persistent to about \n4 to 5 years for a single dose of pentavalent based on the hSBA from the Pfizer clinical trial \nreport. In the CDC model, the duration of protection for pentavalent vaccine was assumed to \nfollow quadrivalent vaccine, while the duration of protection for MenB for a single dose and 2 -\ndose and for the pentavalent was assumed to be following the MenB vaccine. There was \n1 Phase 3 noninferiority initial vaccine efficacy by single dose (at 11-12yrs) and second-dose (16yrs) of pentavalent (Men ABCWY) \nvaccine as reported by Pfizer (data on file); Updated Pfizer Technical reports on Cost-effectiveness of the Pentavalent \nMeningococcal Vaccine (MenABCWY) in the US; Cohn AC, MacNeil JR, Harrison LH, et al. Active Bacterial Core Surveillance \n(ABCs) Team and MeningNet Surveillance Partners. Effectiveness and Duration of Protection of One Dose of a Meningococcal \nConjugate Vaccine. Pediatrics. 2017 Feb;139(2):e20162193. doi: 10.1542/peds.2016-2193. PMID: 28100689; PMCID: PMC8353579; *The range for VE efficacy for first dose of MenB is from Castilla et al. NEJM 2023 \nhttps://www.nejm.org/doi/full/10.1056/nejmoa2206433 \n11 \n \n   \n   \n   \n \n \n     \n   \n   \n  \n    \n  \n      \n    \n   \n \n  \n    \n \n   \n    \n    \n \n      \n  \n \n    \n  \n    \n \n  \n   \n  \n   \n  \n   \n    \n    \n   \n  \n   \n   \n \n   \n  \n     \n      \n uncertainty of the waning assumption beyond available surveillance of Phase 3 data. The CDC \nmodel tried to minimize the inclusion of that uncertainty into the model , whereas the Pfizer \nmodel still showed substantial protection that also influence d the estimates in the end of the \ncost-effective analysis. \nAs in previous analys es, the models used percent of survival cases with specific sequelae as \nreported in the literature. The Pfizer model reports a larger number of long-term sequelae, \nthough there were some with zero value or close to zero probabilities. Over the range of \nsurvivors with sequelae, approximately 28% suffer ed some long-term sequelae in the Pfizer \nmodel. The CDC model focus ed on the most common long-term sequelae among survivors of \nmeningococcal disease infection for which there was a smaller probability of survivors with \nsequela of approximately 21.6%. However, the CFR was very close at 12.5% in the Pfizer \nmodel and the 12.3% in the CDC model . There was differentiation by age group in the Pfizer \nmodel . The difference in the methodology was that in the Pfizer model included life years los t at \nthe end of life for those with sequelae who were included in the Pfizer model, which means that \nfor a specific sequela, multiple amputations, there was a reduction in life expectancy that was \naccounted as the lif e years saved by the vaccination program. \nRegarding medical cost and quality scores, Pfizer medical cost differentiated the type of IMD . \nOn average, medical costs could be twice as much as the costs used by the CDC model . \nRegarding QALY scores, because meningococcal disease follows a rapid clinical course, both models estimated decrease in QALYs associated with the acute illness for survivors of IMD and \nspecifically for the cases without permanent sequelae. These values are different in magnitude. In the CDC model, the quality adjusted life days (QALD) was approximately 46.26 days during \nthe acute phase of the disease, which is only 1/3 to 1/4 of those used for a Pfizer model for the same acute phase during the acute phase of IMD . After the acute phase in cases without \npermanent sequelae, the equivalent QALD was approximately 14 to 15 days in the CDC model, \nwhich was approximately 1/6 the value used by the Pfizer model during the acute phase of the \nIMD. In the CDC model, the values are more conservative than used by Pfizer. \nIn terms of a comparison of the outcomes reported by both models for each of the policy questions, among the main results were the total net cost impact and incremental cost-\neffectiveness of vaccination studies (e.g., incremental health impact in terms of cases, deaths, \nlife years, and QALYs save d) and ICERs. In terms of PICO 1, the incremental effectiveness and \ncost-effectiveness of vaccinating healthy adolescents 11-12 and 16 years old with p entavalent \nvaccine relative to using MenACWY and MenB vaccines , a very important clarification is that to \nmake fair comparison, for the total net cost estimates , cost-saving, and cost per QA LY saved, \nthe analysis used $250 per private dose administered versus $187.50 for the public sector. The \ncumulative probability of ICER per QALY saved for the CDC model, the 5\nth and 95th percentiles \nshowed that the probability of being cost-saving is very high. CDC and Pfizer aim ed to answer \nPICO 2, the incremental effectiveness and cost-effectiveness of vaccinating healthy adolescents 11-12 and 16 years old with p entavalent vaccine relative to using MenACWY only, using the \nupdated lower price per dose for the private sector of $210 and public sector of $157.50 for the \npentavalent vaccine. This analysis showed that the most important variables explaining the variability between the models were related to dis utilities and long-term sequelae. The C DC \nmodel showed that the ICER also was costly at a higher level at more than twice that of the \nincremental cost per QALY as reported by the Pfizer analysis. The incremental cost being \nincrementally costly was correlated by the cumulative probability of simulations in the CDC \nmodel, specifically in that both the 5\nth and the 95th percentiles were positive. In other words, the \nprobability is quite high that in this strategy with 2 doses, the P -P-N is costly relative to the \nstandard of care. \n12 \n \n  \n \n  \n  \n     \n \n   \n \n    \n  \n \n \n \n     \n      \n   \n   \n   \n  \n   \n \n \n    \n   \n   \n   \n   \n     \n     \n     \n  \n \n \n  \n \n \n \n \n   \n \n    \n \n     Both models attempted to answer PICO 3 regarding the incremental effectiveness and cost-\neffectiveness of vaccinating healthy adolescents ≥16 years old with Pentavalent vaccine relative \nto using MenB vaccine only . The estimates of both the incremental health outcomes and net \ncost were compared to be similar relative to the standard of care and coincide in pointing that \nthe Q -P-P would be cost -saving. This fact was corroborated by the cumulative probability of \nsimulations in the CDC model in that the 5th and 85th percentile were negative, meaning that \nthey are cost-saving. These estimates used the updated vaccine price of $210 for the private \nsector and $157.50 for the public sector. \nAmong the limitations are first that factors not considered in the Pfizer and CDC model s may \nresult in overestimating the ICER or underestimating the cost -effectiveness of the pentavalent \nvaccine. In the base-case, both models assumed no protection against non-IMD and no indirect \nprotection against IMD of unvaccinated individuals because they used only a discrete model not \na dynamic model with high immunity components or indirect effects. Productivity losses incurred \nby caregivers for long-term specific sequelae were based on assumptions and were partially \nincluded. Second, differences in key inputs among the Pfizer and CDC model s and the \nuncertainty in input data may explain some of the difference in the results, although it is very \ninteresting to see that there are coincidences as well. The most important elements that drive the difference among these 2 models is the duration of vaccine protection, medical costs , \nvariability in IMD incidence and CFR data, inclusion of different sequalae, and QALY score for \nIMD cases without permanent sequelae. Third, the pentavalent price for Q -P-B is uncertai n. The \nprice used in this analysis was the minimum expected cost as reported by Pfizer. Higher prices will increase total net cost and ICERs . \nIn conclusion, in both models, pentavalent vaccine would reduce the IMD burden in \nadolescents. In both models, strategies with 1 or more doses of the pentavalent vaccine would \nsave more or an equal number of IMD cases. For PICO 1, Q -P-B could be incrementally cost-\nsaving relative to the standard of care, remembering that in this strategy, a dose of pentavalent \nwould be substituted for the second dose of the quadrivalent and the first dose of MenB. For PICO 2 , the strategy that includes 2 doses of pentavalent and nothing else, is incrementally \ncostly, not cost-saving , relative to the standard of care of 2 doses of quadrivalent. For PICO 3 , \nthe model with a quadrivalent followed by pentavalent at 16 years of age and another dose 6 \nmonths after pentavalent , is likely cost -saving relative to the standard of care. About 96% of \niterations in the CDC model simulation have an ICER less than zero. Reasonable pentavalent \nprices and duration of protection combined with careful design of vaccination interventions with pentavalent will determine the cost and cost saving value of the pentavalent vaccine among adolescents ≥11 year of age. \nDiscussion Points  \nReferring to Slide 12 regarding the cost of the pentavalent vaccine for the 2-dose option versus the single dose option, Dr. Loehr noted that the single dose option, Q -P-B, would be $250 and a \n2-dose option (P-P-N and Q -P-P), would be $210. It seemed odd to him as a practicing \nphysician that Pfizer would charge a different amount based on what they decide. He would be purchasing vaccine for his office at a certain price, but they would not know how he is giving it. \nDr. Palumbo (Pfizer) responded that a simplified meningococcal vaccine schedule like Q -P-P \nwould improve vaccination administration and simplify stocking. Pfizer commit s to a list price of \n$210 for a Q -P-P dosing schedule for any combination that includes a 2-dose schedule for the \nPfizer pentavalent vaccine as aligned with the label. In the scenario of a Q -P-B in isolation, \n13 \n \n  \n   \n \n \n \n \n     \n \n     \n   \n  \n \n  \n \n   \n   \n \n   \n \n \n   \n  \n   \n   \n \n \n  \n \n \n   \n    \n  \n \n  \n      \n   \n  \n     \n  \n \n    \n   \n   \n \n \n     \n   \n \n given that this does not align with the FDA-approved 2-dose schedule, Prizer cannot commit to \na price at this time. The previously shared prices of $250 for private and $187.50 for public per \ndose shared in Dr. Ortega-Sanchez's cost-effectiveness model was a minimal price for the \npurposes of economic modeling. \nDr. Talbot observed that this would mean that if the ACIP voted for a Q-P-B strategy, this would \nmean an off-label recommendation for the P and the B b ecause B is 2 doses. \nDr. McNamara responded that a Q-P-B schedule would be off-label for pentavalent and for B \nbecause those are both licensed as a 2-dose series. However, as pointed out earlier, there is no \ninterchangeability between manufacturers of B components. The pentavalent and Trumenba® \ncontain the same component and should be able to be used interchangeably in terms of the \nimmune response, but it is off-label. \nDr. Poehling emphasized that cost -effectiveness is very important in thinking about this. She \nasked Pfizer for clarification about how many doses are in a bottle and whether she was \nunderstanding correctly that the price of the vaccine would vary if it could be used with both Bs, \nand it could be used for 2 doses only if the ACIP said it could be used when both vaccines are \nrecommended. \nDr. Palumbo (Pfizer) responded that bottles contain a single dose and that in any Q-P-P \nscenario or any combination where a Q -P-P is an option, the price will be $210 a dose. The \nproblem with the Q-P-B as already stated is that it is not aligned with the label , so Pfizer has not \nconsidered or finalized pricing for that scenario. For any combination that includes Q-P-P the \nprice is $210 per dose. Dr. Poehling requested that since the ACIP was planning to vote during this meeting, she asked \nthe group to convene to come up with a price in case the vote goes a different way, because that is an important determination. \nDr. Cineas asked whether the standard of care used in both analyses , Q-Q and B-B, takes into \naccount the current B uptake in terms of the cost analysis since that is a shared clinical \ndecision-making recommendation. \nDr. Ortega- Sanchez replied that the 2 models used a static model, which means that only direct \nimpacts of vaccination were taken into account. In order to align both model s, a single similar \nuptake of the vaccines was used so that variation was not included in the base-case analysis. \nThey can definitely include variations in uptake to determine whether that would be mute to the \nincremental cost ratios , because whatever is saved in terms of not giving doses also is not \nsaved in terms of disease prevented and they cancel in the ICER. \nDr. Talbot asked the current price for 1 dose of B, even if giving 2 doses, when the vaccine is \npurchased. In addition, she asked whether Pfizer was insinuating that if the ACIP changes the \nrecommendation to Q -P-B that they would change the price of B . \nDr. Palumbo (Pfizer) reiterated that the Q-P-B scenario does not align with Pfizer’s label, so \nthey would need to consider what the price would be given that. However, if there is an option of \nQ-P-P or any combination where 2 doses of the pentavalent vaccine is an option in which case \nthe price would be $210 per dose. \n14 \n \n   \n \n \n     \n   \n \n    \n  \n \n   \n   \n   \n   \n \n \n    \n \n  \n     \n  \n  \n    \n  \n   \n \n \n   \n \n \n \n \n \n \n  \n   \n \n  \n  \n \n  \n  \n   \n \n  Dr. Talbot clarified that her question regarded the current cost of 1 dose and whether Pfizer \nwould consider changing the price of MenB with a Q-P-B scenario. \nDr. Palumbo (Pfizer) replied that the current cost for Pfizer’s MenB vaccine is $178 for private \nand $130.77 public and that the current price for MenB vaccine would not change. \nDr. Lee said that in this instance, she appreciate s the manufacturer's approach in terms of being \ntransparent about the 2- dose pricing and recognizing that if it is not as it was originally licensed \nfor use, Pfizer would need to reconsider the pricing strategy. She also noted that while she \ntypically is not empathetic, she is empathetic in this instance. Nevertheless, this makes it very \ndifficult to make a decision. She thought the tension Pfizer was hearing was more about the fact \nthat the ACIP has to consider cost-effectiveness in any of its decision-making . The uncertainty \naround the price makes it difficult to assess that, even though there are some ranges and some \nsensitivity analyses. \nDr. Goode (APhA) asked why the P -P-N, which is no extra intervention, would be more costly \nthan a Q -P-P. \nDr. Ortega- Sanchez indicated that for PICO 2, the Pfizer analysis includes the number of cases \nincrementally of IMD cases saved, IMD deaths saved, and life years saved, but the cost is \nbasically due to the new pentavalent vaccine price compared to the cost of the standard of care \n(P-P-N versus Q -Q). When only pentavalent and nothing else is used against the standard of \ncare of 2 doses of quadrivalent vaccine, it becomes costly. In the CDC model for PICO 2, the \nsame analysis was used with the same assumptions and data, but the total per QALY saved \nwas higher ($4.7 million) than the one provided for Pfizer ($1.94 million). All simulations, \nregardless of which ones are positive , means that it will be costly . \nDr. Talbot observed that if P-P-N is used currently with the recommendation of 11 and 12 years \nof age, her understanding was that it would not provide B protection in college. However, if P -P \nis given starting at 16 years of age, that would cover college. Her questions regarded whether P-P-N is cost-effective, but not for B when one gets to college because a B booster would be \nrequired at that time. \nDr. Ortega- Sanchez indicated that because the effectiveness of P -P starting at 11 years of age, \nbecause of the cost the pentavalent vaccine and because they look very similar in terms of \neffectiveness, the strategy of substituting the quadrivalent with the pentavalent is more costly, \nnot c ost-effective. If that is switched to give the 2 pentavalent doses at 16 years of age, that is a \ndifferent question that was not analyzed in these strategies. It was one of the analyses they \nwere thinking of doing, but that is a different type of question. \nDr. Long asked what percentage of older adolescents currently get B vaccine under shared \nclinical decision-making and said she assumed the majority of them are college students. \nDr. McNamara indicated that the last data show that about 30% of those 17 years of age are \ngetting at least 1 dose of serogroup B vaccine. Other data sources show that a little more than  \n50% of those complete the series . Unfortunately, there are not good ways to assess whether \nthe majority are college students. \n15 \n \n  \n \n \n \n   \n    \n  \n \n \n  \n \n \n \n \n \n \n \n    \n  \n \n \n \n \n  \n  \n \n  \n \n  \n  \n \n  \n   \n \n \n \n \n \n \n  \n    \n    \n \n   \n    \n   Dr. Long emphasized that doctors do not like to have to stock many different kinds of vaccines, \nso the least difficult would be to use the combination vaccine. She asked whether the cost-\neffectiveness model took into account that there potentially would be a much higher percentage of MenACWY uptake at this age. \nDr. McNamara indicated that the current MenACWY uptake is in the high 80% range for dose \ngiven to adolescents at 11 to 12 years of age and about 60% for completion of the 2-dose \nseries . There are some data from administrative claim sources that have demonstrated that the \nactual proportion of those 16 to 18 years of age who are current with catch-up \nrecommendations is significantly higher than that as some people don’t get the 11-12 year old dose but get it later . \nDr. Long asked whether the cost-effectiveness model figured in that since the default position \nwould be much less shared clinical decision-making and a much higher percent getting the \ncombination vaccine . \nDr. Ortega- Sanchez reiterated that these are static models that include only direct impact of \nvaccination. In this this type of analysis, uptake is mute in terms of impact on the cost-\neffectiveness ratio. While not giving the vaccine saves dollars, this also does not save the \ndisease. Therefore, both of those values, one in the denominator and one in the numerator, \ncancel and that is why the ICER s and cost per QALY saved remain unchanged and are not \ninfluenced by the coverage or the uptake of the vaccination. \nDr. Long emphasized that the unintended consequences of not preventing disease would be \nextremely costly. \nDr. Lee added that the implication would be that the total cost would be higher , but that does not \nnecessarily impact the cost-effectiveness. She reminded everyone that the ACIP C harter \nspecifically states that the committee consider cost-effectiveness and not necessarily total cost \nin its decision -making. \nMs. McNally asked whether Pfizer could discuss how a shared clinical decision-making \nrecommendation may impact their pricing decision, if at all. Dr. Palumbo (Pfizer) indicated that this would not impact their pricing decision and reiterated \nthat when she talks about “in combination,” if a Q -P-P and a Q -P-B are recommended, the price \nwould be $210 per dose. It is the Q -P-P in isolation that does not align with the label, which they \nwould need to reconsider. \nPfizer Statement \nDr. Luis Jodar (Chief Medical Officer for Pfizer Vaccines/Antivirals and Evidence \nGeneration) emphasized that to be clear so that there are no misunderstandings, when talking about Q -P-P, this is a licensed 2-pentavalent product administered 6 months apart. Once the \nlicensed option is included, other options that include a pentavalent followed by a monovalent B \nare at the same price. It is only the situation in which there is a mixed schedule that is not in the \nlabel, which is a pentavalent and monovalent B, is exclusively recommended when the price \nneeds to be reassessed. To highlight the advantages of a recommendation with the \nquadrivalent at 11 years of age followed by 2 doses of the pentavalent (PENBRAYA™) at 16 \nyears of age given 6 months apart identified as Q -P-P, Pfizer developed PENBRAYA™ in line \n16 \n \n  \n  \n   \n  \n    \n        \n  \n   \n    \n \n  \n \n  \n   \n   \n    \n \n \n    \n \n   \n  \n \n   \n  \n  \n  \n \n   \n   \n   \n  \n \n  \n \n    \n \n \n \n     \n  \n   \n \n \n  \n  \n \n \n   with the CDC ’s General Best Practice Guidelines for Immunization.2 In general, he said he \nthought they all could agree that licensed combination vaccines can improve vaccine uptake, \nvaccine compliance, and reduce the number of injections individual s receive. Recommending 2 \ndoses of PENBRAYA™, the Q-P-P strategy , would simplify the current standard of care by \nreducing the number of injections from 4 to 3 to help protect adolescents and young adults \nagainst all 5 serogroups . This strategy can be accomplished by stocking only 2 vaccines, \nwhereas the mixed Q -P-B strategy would require healthcare providers ( HCPs ) to stock 3 \nvaccines (e.g., quadrivalent, pentavalent, and monovalent B vaccines ). This would add \ncomplexity, costs , and the potential for errors. \nAdditionally, administration of the monovalent MenB vaccine is not necessarily equitable across \nthe US with adolescents residing in rural areas and Black and Latino adolescents having lower coverage. Pfizer’s believes that PENBRAYA™ is a tool that could at least help close these \nequity gaps. The 2 doses of PENBRAYA™ are given 6 months apart, which is the schedule \nbased on the clinical data and the only one that is aligned with the FDA label. It is estimated that \nimplementation of 2 doses of PENBRAYA could prevent more cases and deaths caused by IMD \ncompared to the current standard of care. The proposed Q -P-P schedule will reduce costs \ncompared to the current standard of care. PENBRAYA ™ will cost approximately 43% less than \nif the ACWY and B vaccines are administered separately. That was why Pfizer wanted to \nemphasize this price. In fact, Pfizer is committed to making the vaccine available at a similar \nprice to an individual MenB vaccine, thus ensuring that the FDA indicated use of 2 doses is the most cost-sav ing option for the meningococcal vaccine program. \nDr. Jodar respectfully urged the ACIP to take up this policy and make recommendations of the \nuse of the pentavalent meningococcal vaccine during this meeting. HCP around the country \nlook to the ACIP as experts that set the standards of practice. Silence from ACIP until 2025 will \nhave negative effects on vaccine confidence and avoid information where suboptimal practices \ncan emerge. Recommendations from ACIP should ensure on -label use of the vaccine and will \nresult in better real -world safety and effectiveness data over the next year that the ACIP \ncampaign used to revisit recommendation on the entire meningococcal platform. He thanked the \ncommittee for these complex deliberations to optimize the meningococcal vaccine platform and \nexpressed hope that the simplicity , advantages, and cost savings of the Q-P-P strategy can \ntranslate into public health benefit and accessibility to everyone. \nDr. Kimberlin (AAP Redbook) asked if on slide 18, is SOC in the table Q -Q + B -B?  And on slide \n21, what is SOC? Dr. Ortega- Sanchez indicated on slide 18, it is Q -Q+B -B, and on slide 21 it is Q -Q+B -B. \nSummary of EtR and Proposed Recommendations for Pfizer’s MenABCWY Vaccine \nDr. Jennifer Collins (CDC/NCIRD) presented a summary of the EtR framework and the \nproposed recommendation for Pfizer ’s MenABCWY vaccine. As a reminder, current ACIP \nrecommendations for meningococcal vaccines are as follows: \nRoutine Schedule \nMenACWY: dose 1 at age 11– 12 years, booster dose at age 16 years \nMenB (shared clinical decision-making): 2 doses at age 16– 23 years (preferred age 16– 18 \nyears) \n2 https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/index.html \n17 \n \n  \n \n \n \n \n \n \n \n \n \n  \n \n \n   \n \n \n    \n \n   \n \n \n  \n \n \n  \n  \n \nS\npecial Situations \nMeningococcal vaccines that are licensed and available in the US are interchangeable and \ninclude: \nMenB vaccines are not interchangeable, and include: \nPfizer's pentavalent MenABCWY vaccine is now licensed as a 2-dose series with a 6- month \ninterval for individuals aged 10─ 25 years. As a reminder, the pentavalent vaccine is comprised \nof Trumenba™, Pfizer's MenB vaccine that is currently licensed and available in the US, and Nimenrix ™, Pfizer’ s MenACWY vaccine that is not licensed in the US, but has been used \nextensively in Europe and elsewhere for more than a decade. \nThe Meningococcal WG addressed 3 policy questions for the following PICOs: \n1. Should the pentavalent vaccine be included as an option for MenACWY/MenB vaccination \nin people currently recommended to receive both vaccines? (PICO 1) \n2. Should the pentavalent vaccine be included as an option for people currently recommended \nto receive MenACWY only? (PICO 2) \n3. Should the pentavalent vaccine be included as an option for people currently recommended to receive MenB only? (PICO 3) \n18 \n \n  \n \n  \n  \n  \n \n    \n  \n  \n  \n   \n   \n \n \n \n   \n \n \n \n \n   \n  \n  \n     \n   \n   \n    \n   \n    \n \n  \n  \n  \n   \n  \n   \n \n \n  \n The population is individuals aged 10 years or older currently recommended to receive \nMenACWY+MenB, MenACWY, or MenB vaccine . The intervention is vaccination with Pfizer ’s \npentavalent vaccine. The comparison varies by the policy question. The 6 outcomes that were \nassessed through the GRADE process include: \n1. Meningococcal disease caused by serogroups A, B, C, W, and Y (as appropriate by PICO) \n2. Short-term immunity \n3. Persistent immunity \n4. Interference with other recommended vaccines administered concurrently \n5. Serious adverse events (SAEs) \n6. Non-serious AEs \nThis table shows how the PICOs were translated into schedule options for healthy adolescents \nfor the purposes of the GRADE assessment and the economic analysis. As a reminder, Q stands for the quadrivalent vaccine (MenACWY ), B for MenB, and P for the pentavalent \nvaccine : \nRecall that these options assumed that vaccinations were given first at ages 11─12 years when \nthe first quadrivalent dose is recommended, with subsequent vaccinations at age 16 years when \nthe second quadrivalent dose is recommended. However, as discussed during the June ACIP \nmeeting and earlier during this meeting, 16 years of age often is not optimal timing for the MenB \ncomponent. To summarize the WG consensus presented during the June 2023 ACIP meeting, \nthe WG was in favor of PICO 1 or Q -P-B. The WG was not in favor of PICO 2 or P -P-B. The WG \nwas divided regarding PICO 3 or Q-P-P. Since that time, the WG refined the EtR framework and \nfurther considered possible implications of each PICO, especially PICO 3, based on concerns \nraised by ACIP members during the June 2023 meeting regarding the following: \nCost-effectiveness concerns about all options, including the current schedule \nConcerns about increasing exposure to B component vaccines related to reactogenicity, low \nburden of disease, and limitations to protection \nThe concern that the optimal timing of B component is often not age 16 years \nFidelity to clinical trial data, licensure, and stocking concerns \nStocking and administration considerations \nAs presented earlier, the cost-effectiveness analysis was revised to reflect updates to the quoted price of the pentavalent vaccine and to incorporate refinements to the CDC model. \n19 \n \n   \n  \n  \n  \n \n \n   \n     \n   \n \n \n \n  \n    \n    \n \n   \n    \n    \n    \n   \n  \n   \n  \n  \n    \n  \n \n    \n   \n  \n   \n \n \n  \n  \n \n   \n  \n   \n   \n  \n \n  \n   \n      \n   \n  To summarize the updated EtR, for the public health problem domain, members noted that the \nincidence of meningococcal disease is low and decreasing, but that it causes very severe \ndisease and poor outcomes even with treatment. The case fatality rate is 10% to 15% and 10% \nto 20% of survivors have permanent sequelae. The WG interpretation for public health problem for all three PICOs was that yes, meningococcal disease is a problem of public health \nimportance. \nRegarding benefits and harms, 3 randomized control trials (RCTs) studied the pentavalent \nvaccine 2 dose intervals (0, 6 months and 0, 12 months) versus MenACWY -CRM 1 dose + \nMenB -FHbp 2 doses (0, 6 months) . The studies were conducted among both ACWY -naïve and \nACWY -primed participants. Available data facilitated assessment of select outcomes through \nGRADE . Other important benefits and harms were not assessed through GRADE but were \nfactored into the WG interpretations. These included increased reactogenicity of MenB relative \nto MenACWY and limitations to B protection, including that low VE is expected following a single \ndose, rapidly waning protection following a 2-dose series , and multiple studies demonstrating \nthat MenB vaccination has no effect on meningococcal carriage. \nTo summarize the GRADE assessment for benefits, no data were available to assess the critical \noutcome of meningococcal disease caused by serogroups A, B, C, W and Y. For the critical \noutcome of short-term immunity, data were available from 1 RCT. Serogroup-specific \nseroresponses 1 month after the first trial dose of ACWY - or B-containing vaccine occurred as \noften or more often in the pentavalent group compared with the control group. The evidence \ntype was moderate for healthy persons and low for those at increased risk. For the important \nbenefit of persistent immunity, d ata were available from 2 RCTs . Seroresponse rates by \nserogroup were similar between groups. The evidence type was low to moderate for healthy \nindividuals depending on serogroup and low for those at increased risk. For the critical outcome \nof SAEs, data were available from 3 RCTs . Significantly more SAEs occurred in the pentavalent \ngroup versus the comparison group, though none were attributed to the vaccine. The evidence \ntype was low for healthy individuals and very low for those at increased risk. For the important \noutcome of non-serious AEs, data were available from 3 RCTs . Significantly more non-serious \nAEs occurred in the pentavalent group versus the comparison group. The evidence type was \nlow for healthy individuals and very low for those at increased risk. No data were available to \nassess the important outcome of interference with other recommended vaccines administered \nconcurrently. \nFor PICO 1, the WG interpretation was that the desirable and undesirable anticipated effects \nwere small, and they favored the intervention, with overall certainty varying by group. For PICO \n2, the WG interpretation was that the desirable anticipated effects were minimal to moderate, \nundesirable anticipated effects were minimal or small, and the balance favored the intervention, \ncomparison, or both and overall certainty varied by group. For PICO 3, the WG interpretation \nwas that the desirable anticipated effects were minimal, the undesirable anticipated effects were \nminimal or small, and the balance favor ed the intervention or comparison. Overall certainty \nvaried by group. \nRegarding the values of the target population, limited data were available. The WG noted that \namong adolescents during 2021, vaccination coverage of at least 1 dose was 89% for \nMenACWY and 31% for MenB. Limited data were available on vaccine uptake in other \nindividuals recommended to receive MenACWY or MenB vaccine. In general, use of combination vaccines can reduce the number of injections and is generally preferred over \n20 \n \n   \n \n  \n  \n \n    \n \n \n     \n    \n  \n   \n   \n  \n   \n \n \n   \n   \n \n \n      \n  \n  \n \n \n \n  \n    \n \n \n    \n   \n   \n \n  \n \n    \n   \n   \n  \n  \n    \n    \n    \n \n \n \n separate injections of the equivalent component vaccines.3 For the first values domain question \nregarding whether the target population feel s that desirable effects were large relative to \nundesirable effects, the WG interpretations were “probably yes ” for PICOs 1 and 2 and \n“probably yes ” or “don't know ” for PICO 3. For the second values domain question regarding \nwhether there is important uncertainty or variability in how much people value the main \noutcome, the WG interpretation was “probably no” for PICO 1 and “probably yes ” for PICOs 2 \nand 3. \nFor the acceptability domain, limited data were available. The WG noted that acceptability likely \ndepends on the PICO and balance of stakeholder values. HCP are likely supportive of options \nthat allow stocking fewer vaccines. Pentavalent vaccines have the potential to increase \nvaccination rates against serogroup B disease and can reduce the number of injections from 4 \nto 3 for some patients. However, pentavalent vaccines also have the potential to incentivize \nMenB administration at 16 years of age with waning immunity by the time of peak risk for some \npatients. Many providers prefer to wait until closer to exposure to congregate settings , such as \ncollege or the military. ACIP and WG members also have expressed concerns about increasing \nexposure to MenB component vaccines , which are more reactogenic than MenACWY vaccines, \nparticularly when the burden of MenB disease is already low despite low vaccine coverage. The \nWG interpretations for acceptability were “probably yes ” or “yes” for PICOs 1 and 2 and “don't \nknow” for PICO 3. \nFor the resource use domain, ACIP and WG members have noted that all proposed \nmeningococcal vaccine strategies are expensive, including currently recommended options for \nadolescents. With the new price estimates, Q -P-P is the most cost-effective option when MenB \nprotection is desired. The WG interpretations were “probably yes ” or “yes ” for PICO 1, “probably \nno” or “no” for PICO 2, and “probably yes ” or “yes ” for PICO 3. \nFor the equity domain, limited data were available. WG members felt that the pentavalent \nvaccine is not expected to negatively impact equity. It potentially could reduce disparities among \nthose who might be interested in being vaccinated against serogroup B, but who might not otherwise receive clinical care that includes discussion of the MenB vaccine. WG members also discussed the possible risk of clinics not stocking monovalent B vaccines with some policy options , which could affect availability for outbreaks and for people at increased risk of \nmeningococcal disease who are recommended to receive 3 doses of MenB-FHbp. The WG \ninterpretations for equity were “probably no impact” or “varies ” for PICO 1, ”probably increased,” \nvaries,” or “ don't know” for PICO 2, and “don't know ” for PICO 3. \nRegarding whether the intervention is feasible to implement, the WG felt challenges with \ninsurance coverage specific to the pentavalent vaccine are not expected. Substantial financial \nburdens for providers or health systems also are not expected. The pentavalent vaccine would \nprovide an additional option in the current schedule and may reduce the number of doses for some people. However, administration requires reconstitution, which may lead to administration errors. St ocking 3 different meningococcal vaccine types also may be prohibitive for some \nproviders. The lack of B vaccine interchangeability complicates stocking considerations. The \nWG interpretations for feasibility were “probably yes ” or “yes ” for all 3 PICOs. \n3 General Best Practice Guidelines for Immunization. Best Practice Guidance of the ACIP. https://www.cdc.gov/vaccines/hcp/acip-\nrecs/general-recs/downloads/general-recs.pdf ; and American Academy of Pediatrics. Red Book 2018. Report of the Committee on \nInfectious Diseases. 31st Ed. https://seciss.facmed.unam.mx/wp-content/uploads/2021/02/Red-Book-31th-Edition.pdf \n21 \n \n   \n  \n  \n \n \n  \n \n  \n   \n \n   \n \n  \n  \n   \n \n  \n \n \n  \n  \n  \n \n  \n    \n  \n \n  \n  \n \n \n \n \n \n \n \n   \n  \n To summarize the EtR domains and WG interpretations for each of the 3 PICOs , for PICO 1 \nWG judgements were generally supportive, less so for PICO 2 with more uncertainty, and PICO \n3 had the most uncertainty. A summary of the WG consensus and debate regarding the PICOs \nis shown here: \nStrong consensus in favor of PICO 1: MenABCWY as an option for MenACWY + MenB \n(QPB) \nStrong consensus against PICO 2: MenABCWY as an option for MenACWY only (PPB) \nLimited consensus regarding PICO 3: MenABCWY as an option for MenB only \nThe options the WG debated for PICO 3 included the following: \nOption A: Reject PICO 3 outright \nOption B: Accept PICO 3 with limitations allowing for Q -P-P only \nOption C: Accept PICO 3 fully, which would allow for Q -P-P and other options \nThis differentiation between Options B and C is new since June. In terms of the existing recommendations for the routine schedule incorporating shared clinical decision-making, the \nfirst dose of quadrivalent vaccine is recommended at 11 to 12 years of age with a second dose \nat 16 years of age. Shared clinical decision-making may result in no B vaccination , B \nvaccination at age 16 years, or B vaccination at an age greater than 16 years. Although this is \nrelatively straightforward, introduction of the pentavalent vaccine adds complexity. Option A \nadds Q -P-B to the existing options. That is , per the consensus in favor of PICO 1, the \npentavalent vaccine could be given in lieu of MenACWY and MenB when both vaccines are \nindicated. Because PICO 3 is rejected with Option A, the pentavalent vaccine would not be used \nin lieu of MenB only. The remaining MenB vaccine would therefore be monovalent. The \ndifference between the 2 Q-P-B options relates to the interval between the pentavalent vaccine \nand the subsequent monovalent B vaccine. Notably, neither option is consistent with the \nlicensure for a 2-dose pentavalent or MenB series, and there is a lack of data regarding \nimmunogenicity with extended intervals between B doses. Option B adds Q -P-P to Option A. \nThat is , if an initial dose of pentavalent vaccine was given at age 16 years, a second dose could \nbe given 6 months later within the licensed indications to complete the meningococcal vaccine \nseries. Apart from this limited circumstance, pentavalent vaccine would not be used to replace MenB. Option C adds Q -Q-P-P and Q -Q-P-B to Option B. That is , in accepting PICO 3 fully, the \npentavalent vaccine could be given in lieu of MenB even after the MenACWY series has been \ncompleted. \nWith this increased flexibility comes a higher cost and a lack of data on safety and immunogenicity of pentavalent vaccines in individuals primed with 2 doses of quadrivalent \nvaccine. Notably, Q -Q-P-P and Q -Q-P-B options were not assessed through GRADE. In \n22 \n \n    \n  \n \n \n    \n   \n  \n  \n      \n    \n \n \n \n \n    \n  \n  \n    \n   \n \n  \n   \n \n   \n  \n  \n \n  \n \n \n \n \n \n \n \n   \n    \n \n \n \n \n \n \n \n \n    \n  \n \n    \n summary, all 3 options considered by the WG would permit the current standard of care of QQ \nversus QQBB under shared clinical decision-making. Option A adds QPB, Option B adds QPP \non top of that and Option C adds QQPP and QQPB to Option B. \nTo summarize Options A, B, and C , Option B had the most favorable ratings overall. Option B is \nbest aligned with clinical trial data and proposed licensure and provides only 1 excess dose of \nMenACWY. It also provides intermediate flexibility to stock 2 vaccines if using the pentavalent \nvaccine for routine indications, assuming MenB at age 16 years. However, all options would \nrequire stocking 3 vaccines for special situations , though 2 vaccines could be stocked \nregardless if using only MenACWY and MenB. Option B also was the most cost-effective option \nbased on recent price updates from Pfizer . WG members felt there was lower potential for \ninsurance reimbursement issues . \nFor the balance of consequences for PICO 1, the pentavalent vaccine is an option for \nMenACWY + MenB. The majority of WG members thought that desirable consequences \n“probably ” or “clearly ” outweigh undesirable consequences in most settings. For PICO 1, the \nmajority of WG members favored recommending the intervention. For PICO 2, the pentavalent vaccine as an option for MenACWY only , the majority of WG members thought the undesirable \nconsequences “clearly ” or “probably ” outweigh the desirable consequences in most settings. For \nPICO 2, the majority of WG members favored not recommending the intervention. For PICO 3, the pentavalent vaccine is an option for MenB. The WG did not reach a majority consensus on \nthe balance of consequences and were evenly split among the 3 options . \nFor the WG interpretation of PICO 3, an additional option was added because some WG \nmembers favored Q -P-P only. WG members were divided regarding PICO 3. The majority of \nWG members favored PICO 3 i n some form. However, a substantial minority of WG members \nfavored rejecting PICO 3 outright (Option A). The WG agreed to present Option B, Q -P-P, as a \ncompromise to the committee for further deliberation. The combined draft proposal for Option B \nis as follows: \nPfizer’s MenABCWY vaccine may be used when both MenACWY and MenB are indicated at the same visit. *If MenABCWY is administered in this way, a second dose of MenABCWY may be administered 6 months later to complete the series. \nThe footnote reads : \n*1) Healthy individuals aged 16– 23 years (routine schedule) when shared clinical \ndecision-making favors administration of MenB vaccination, 2) individuals aged 10 years \nand older at increased risk of meningococcal disease (e.g., due to persistent \ncomplement deficiencies, complement inhibitor use, or functional or anatomic asplenia) \ndue for both vaccines. \nThe WG also wanted to include the following remarks, which are not part of the proposal language: \nRemarks: \n• For Pfizer's pentavalent vaccine, data are not available regarding safety or \nimmunogenicity of dosing intervals exceeding 12 months. \n• The licensed B component vaccines are not interchangeable by manufacturer. \nAdministration of a B component vaccine requires that subsequent B component vaccine (MenB or MenABCWY) doses be from the same manufacturer. \n23 \n \n  \n \n   \n \n \n   \n  \n   \n  \n  \n  \n     \n   \n  \n  \n    \n    \n \n \n \n \n \n    \n \n \n \n  \n  \n \n \n \n \n \n \n    \n      \n   \n \n  \n  \n   \n    \n \n \n  • The minimum interval for Pfizer's MenABCWY vaccine is 6 months. Individuals at \nincreased risk for meningococcal disease who are recommended to receive additional doses of MenACWY and MenB, less than 6 months after a dose of pentavalent meningococcal vaccine should instead receive separate vaccines . \nThe rationale in favor of the combined draft proposal is that it aligns with clinical trial data and licensure; allows for fewer doses than QQBB; and provides flexibility with vaccine inventory, \nincluding for clinics that prefer to sto ck 2 vaccines for routine indications, assuming MenB at age \n16 years. In addition, stocking fewer vaccines may increase equity (e.g., if under -resourced \nclinics are less likely to st ock 3 vaccines). This is the most cost-effective option based on the \nrecent price update from P fizer. The rational against the combined draft proposal was that it has \nunnecessary ACWY antigen exposure for the second pentavalent dose in the routine schedule when only MenB is indicated. In addition, there is as much flexibility for providers as in Option 3. \nGeneral considerations against all options include the potential to incentivize MenB at age 16 \nyears with waning immunity by peak risk for some patients, such as those entering college or \nthe military . There also is uncertainty regarding the cost estimates . If using the pentavalent \nvaccine, it will be necessary to sto ck 3 vaccines to cover all indications (routine schedule + \nspecial situations) , which may be challenging for some vaccine providers. \nDiscussion Points \nDr. Talbot requested clarification about how clinical decision-making would work if someone \nreceives B through shared clinical decision-making then receives Q as the second dose, whether they would have to have shared clinical decision-making of Q versus P and then w ould \nhave to have shared clinical decision-making if they decide to receive B, or if they had already decided to do B if they did P. If it is shared clinical decision- making, it seems that all 3 vaccines \nwould need to be stocked (Q, P, and B ). \nDr. Poehling said that when she would embark on this conversation would be at the time of the second dose to indicate that there are 2 types, ACWY and B, and then go through which ones \nwould be done. If B will be included, she would explain that it could be done separately or all \ntogether . It would be shared clinical decision-making for B regardless. A very small clinic might \nelect to carry B in the pentavalent vaccine and perhaps refer those who want only B to a health \ndepartment. A larger organization probably would opt to carry all 3. \nDr. Long emphasized that the ACIP did not decide to make this combination vaccine. \nMeningococcal disease is the only thing putting them together, and it would be easy to advertise \nthis as the full meningococcal panel. But meningococcal diseases, as uncommon as they are, are also extremely different in that secondary cases occur very quickly with C, W, and Y and it is \ndifficult to recognize if there even is an outbreak of B because it may be 2 cases over 3 months \nor 3 cases over 18 months. It is a vaccine that is much better targeted for outbreak use because \nit also has a very short period for which it provides terrific efficacy. Another difficulty is that the \nexisting schedule already is not quite right because the prevention of B starts later than the \nsecond dose of CWY. It is difficult for the ACIP to come up with much that would be good \nutilization of funds and resources if they try to put these together ever. She is very cognizant \nthat not one more antigen should be given than needed. A lthough this has been done with \ncombination vaccines for small children when they are receiving so many vaccines concurrently, \nthat is not the case here. She inquired about whether there could be an amendment prior to the \nproposed vote to not vote. \n24 \n \n   \n   \n \n   \n   \n   \n    \n  \n  \n   \n \n \n  \n   \n \n  \n \n \n \n \n \n \n  \n   \n     \n    \n    \n     \n \n \n   \n    \n \n  \n    \n \n  \n    \n \n  \n   \n  Dr. Kotton said that as an adult provider, she did not want to comment on the pediatric issues, \nwhich are complicated. However, she administers many doses of meningococcal vaccine— \nespecially to people who have had splenectomies. She remains astounded at the number of \nAmericans who have had splenectomies who are under -vaccinated. In her experience, she \nwould estimate that well over 80% of people who have had splenectomies are poorly \nvaccinated. It would be good to offer them an easy option. Furthermore, she sees people who \nare going to become immunocompromised, who are thinking about starting e culizumab and \nother similar drugs that greatly increase the risk of meningococcal disease. Although she is \nexcited about the opportunity to have a pentavalent vaccine because she often is giving so \nmany vaccines in clinic that it becomes onerous to the patient. When they have to have 2 different vaccines or when she is sending them to a commercial pharmacy and they have to get 2 different vaccines, it is very complicated. The fact that she would need to separate the \npentavalent by at least 6 months, usually my patients do not have 6 months to wait, and they \nmay not return for a vaccine. This is really onerous and problematic and very messy. \nVaccination for Americans needs a simpler process. Being a clinician deep in the trenches is \nreally challenging these days and they need to provide simplicity. \nDr. Loehr asked if the ACIP voted/made a recommendation on the pentavalent vaccine during \nthis meeting how that would affect future pentavalent vaccines in terms of whether there would \nbe a new vote or if this vote would apply to new vaccines. \nDr. Wharton indicated that it would depend on the characteristics of future pentavalent vaccines. \nIf the licensed indications are close to the same as this product, it probably could apply to a future vaccine. If there are meaningful differences, it would be brought back to the committee. \nAs a member of the Meningitis WG, he has been a strong proponent for the Q -P-B option. \nWhen this all started, he was thinking of it as an opportunity to give one less vaccine. However, \nhe did not want to give extra antigens to people. Someone pointed out that some clinics might \nstock only a pentavalent vaccine, which had not occurred to him. There is no way he wants to \ngive a pentavalent vaccine to an 11- year-old because B is not necessary at that time, which he \nthought was why many of the WG members voted against PICO 2. He likes the concept of not \ngiving extra antigens and was trying to make a decision on how to vote, because that is a \nseparate issue. The cost -effectiveness that was an issue is no longer an issue because Pfizer \nchanged the price. He said he was disgruntled by the way Pfizer changed the price and the way \nthey framed it, but that is the way it is and we have to accept reality as it is. Some parents ask \nhim if he can use a different schedule for their children’s vaccines. He tells them that they can, \nbut he recommends the schedule as it is because those are the data they have. He realized that if he votes for Q-P-B, that is off-label and is not the schedule the way it was studied. That is a \nsignificant issue for him. He wanted to make sure they always have shared clinical decision-making for B. He is probably going to need to stock 3 vaccines anyway, because he is going to \nhave some people who do not want B and he will need Q. It is just going to be complicated, so he likely would vote for the Q-P-B option, but was less starkly in favor of that than he was over \nthe last 2 to 3 months. \nDr. Daley said he was struggling and thought that the vaccines were not well -matched. While he \nis grateful that there are vaccines to prevent meningococcal disease given its severity, now \nthere is a set of vaccines and a schedule that are not well -matched with the epidemiology . In \nterms of Dr. Talbot’s question earlier about not making a recommendation during this meeting, he is generally not in favor of “kicking the can down the road.” Given that it is a licensed vaccine, the ACIP should provide some guidance. However, it is problematic that they were re-\nevaluating the entire schedule as they were voting and there was the added uncertainty about \n25 \n \n   \n  \n    \n   \n    \n  \n   \n  \n  \n \n \n   \n   \n       \n    \n   \n    \n   \n   \n  \n   \n     \n    \n   \n    \n    \n       \n   \n \n   \n \n   \n  \n  \n  \n       \n  \n \n \n   \n      \n \n  \n     \n   \n   \n      \n  the cost-effectiveness. He said he also thought that sometimes , there is a benefit of having a \nmonovalent MenB vaccine, because that provides flexibility to time the dose when it is most \neffective for the circumstance. Dr. Long said it beautifully. In outbreaks , it is short-term \nprotection. It is important for the ACIP always to think about unintended negative \nconsequences . If there is a lot less monovalent MenB, that removes a tool from the toolbox. \nWhile he was still struggling, he said he was in favor or either not voting on a pentavalent use \nduring this meeting, recogniz ing that would be problematic for the ACIP and the manufacturer \nwho cannot plan as well, or making narrow recommendations. By “narrow” he explained that he \nwould favor PICO 1, but with narrow recommendations because they would revisit this in the \ncontext of an overall conversation about how to best tailor the schedule for the epidemiology \nand resource use. \nDr. Lee said that at this point, she wanted to express the areas where she felt most strongly \nabout this particular decision. She agreed that the benefit-risk balance in minimizing \nunnecessary exposure to antigens was an important one and that the reason this was \ncomplicated was due to the way the current schedule is set up. Recognizing that their \ncolleagues had some work to do and thinking about how the post-COVID epidemiology had \nperhaps changed the benefit-risk balance, she also recognized the need for rigorous evaluation. \nShe favored the Q-P-B option at this point. It’s a choice of a product people can have. Her \nthinking was that a pediatrician could stock QQ with shared clinical decision-making for QQ and \nBB as the options. But if people have a preference, or they want to have a product choice, they could decide to replace the QB combination with a pentavalent. Having said this, she realized \nthat it sounded very confusing and challenging, especially for frontline clinicians. She would \nframe this not as the recommendation, but rather as a choice for people to make, and they \ncould stick with the original schedule. As Dr. Kotton mentioned, there are situations in which \ntransplant patients are being vaccinated who need protection for both. In those instances, she \ncould imagine giving PP in those instances as an option for those high-risk individuals. If they \nassume that the current schedule remains with an option for people to choose to receive QPB \nas an alternative, recognizing the complexities of that, it would give the ACIP the opportunity to \nmove toward a PP schedule in the future as they start to think about the ages. But one thing I did want to clarify and ask, actually two things. Referring to the special situations listed on Slide 2, there is some dissonance in terms of the risk -based categories for ACWY and B. She asked \nwhether the WG could make that simple because the inconsistency makes it challenging. \nWith regard to the dissonance between the MenACWY and MenB recommendations , Dr. \nMcNamara pointed out that these are longstanding recommendations that have reasons behind \nthem. The epidemiology showed that among people with HIV infection in the US , there was a \npredominance of CWY disease and not B disease. Similarly, travel to hyperendemic areas is largely about the African Meningitis Belt where there is no serogroup B. They can look at this in \nreviewing the schedule over the next year to determine if there are opportunities to better \nharmonize, but probably could not make changes during this meeting. \nDr. Poehling added that the reason first year college students and military recruits are not \nchecked on the special situations table is because the MenB column is ≥10 years of age. \nDr. McNamara noted that the recommendations for first year college students and military \nrecruits, the recommendations are for people who did not receive MenACWY vaccines already, \nso they are not current for ACWY per their routine adolescence schedule . There is a shared \nclinical decision-making recommendation for serogroup B in the adolescent schedule, so \nsomeone who has not received those is not considered not up-to-date. \n26 \n \n    \n      \n \n \n \n    \n     \n \n  \n  \n    \n   \n \n  \n   \n \n \n \n   \n  \n    \n   \n   \n    \n       \n     \n      \n \n \n \n \n \n \n     \n  \n \n \n     \n      \n    \n    \n  \n    \n \n \n    Dr. Poehling thanked everyone for wrestling with this , which was not easy and the conversation \nis appreciated. If the ACIP voted for the QPP, which was included in PICO 3, that has an extra \nACWY dose administration. That has occurred with other combination vaccines, so she wanted \nto put it in the context of the current vaccine schedule. \nDr. Sanchez emphasized that meningococcal recommendations are confusing and always have \nbeen, at least to him. He understood the concern regarding minimizing antigen exposure, and they have heard about combination vaccines that result in exposure to more than 3 doses, such \nas Hepatitis B and with the tetanus recommendation in which one can receive acellular \npertussis and diphtheria rather than just a tetanus monovalent. This is known to be safe, so he \nwas not as concerned about this . The biggest issue to him was the that if the pentavalent \nvaccine was recommended for meningococcal B, that also would expose adolescents 11 to 12 \nyears of age to antigens that are not needed until later. It seemed reasonable to offer the \npentavalent vaccine if they also are recommended to receive the meningococcal B component \nfor college entry. Many states require that as well, so it seemed like a reasonable option in \ncertain circumstances versus universally. It certainly would reduce the number of doses of \ninjections given. He asked what data are available on simultaneous administration of other vaccines with the pentavalent meningococcal vaccine. \nDr. Collins indicated that direct data are not available on concomitant administration of the \npentavalent vaccine with other vaccines. They best they could do was to look at Nimenrix, which \nis the MenACWY component in the pentavalent vaccine. Information from the package insert\n4 \nstates that, “Safety and immunogenicity of Nimenrix was evaluated when sequentially \nadministered or co-administered with a DTaP/IPV/Hib/HepB  vaccine in the second year of life. \nThe administration of Nimenrix 1 month after the DTaP /IPV/ Hib/HepB vaccine resulted in lower \nMenA, MenC, and MenW135 Geometric Mean Titers (GMTs) as measured with a serum \nbactericidal assay using rabbit complement (rSBA) . The clinical relevance of this observation is \nunknown, since at least 99.4% of subjects (N=178) had rSBA titer s of ≥8 for each group (A, C, \nW-135, and Y) .” Guidance is provided in the package insert stating that “Whenever possible, \nNimenrix and a tetanus toxoid (TT) containing vaccines , such as DTaP/IPV/Hib/HepB vaccine, \nshould be co-administered or Nimenrix should be administered at least 1 month before the TT-containing vaccine. One month after co-administration with a combined tetanus toxoid, reduced \ndiphtheria toxoid and acellular pertussis vaccine, there were lower GMCs observed for each of the pertussis antigens and more than 98% of subjects and antibody levels above the thresholds.  Again, the clinical relevance of this observation is unknown. There are no data with the \npneumococcal conjugate vaccine. \nDr. McNamara noted that the current licensed meningococcal ACWY vaccines in the US also \nhave some similar interference with the pertussis -containing vaccines. Similarly , the clinical \nrelevance of those observations is unknown and so there have not been recommendations to \ndate about not providing those vaccines concomitantly. \nDr. Talbot said she greatly appreciates the need for the ACIP to review FDA -approved vaccines \nquickly for vaccines that are coming to market. In the cases of RSV and COVID, that was \ncritical. However, this has diverted the ACIP away from reviewing the meningococcal guidelines \nfirst and has been a distraction. In that vein, and at the risk of having everyone on the \nMeningococcal WG angry with her, she asked if it would be possible to accelerate the planned \nreview of the guidelines so that the ACIP could vote in June 2024 instead of later. \n4 https://labeling.pfizer.com/ShowLabeling.aspx?id=12217 \n27 \n \n  \n  \n  \n  \n \n \n \n \n \n \n  \n \n \n \n     \n  \n \n \n \n \n \n \n \n \n \n \n \n \n   \n    \n \n \n \n \n  \n \n \n  \n   Dr. McNamara indicated that they are still seeking a permanent replacement to serve as the \nMeningococcal WG lead, so she could not comment on acceleration. This has been considered \nextensively and there is a lot of work to do in terms of reviewing the adolescent schedule. \nExtended interval data for pentavalent vaccines administered ≥3 years apart is anticipated to \nbecome available over the next year, though an exact date is unknown. This information is \nimportant in terms of considering different vaccine schedule options. Speaking for herself, she \nwould be hesitant to change the schedule in advance of having those data because she would not want to change the schedule twice. \nDr. Lee emphasized that she thought the ACIP needed to vote during this meeting, though \nmembers were free to vote not to make a recommendation. \nDr. Loehr recognized that it was nice to have an option for patients and to have a safe and \neffective vaccine option, and thanked the manufacturer for presenting this and making it \navailable. He asked Dr. Wharton to inform the ACIP on Robert’ s Rules of O rder in terms of \nwhether it would be better to make a motion for a vote and then have someone try to table it or to make a motion to table it first. \nDr. Wharton pointed out that they could not table a vote that had not been moved. If a \ncommittee member want ed to move this toward a vote during this meeting, they should make a \nmotion to that effect. If the motion was seconded and someone wants to amend the recommendation, they could make that motion. Then the debate would be on the amendment rather than the original motion. \nDr. Loehr made a motion in favor of the Combined Draft Proposal for Option B for the \nACIP to accept the language as proposed in Dr. Collins’ presentation Slide 38. Dr. Sanchez seconded the motion for the ACIP to adopt the recommendation language as \nproposed. \nDr. Collins read the language for the record: \nPfizer’s MenABCWY vaccine may be used when both MenACWY and MenB are \nindicated at the same visit. *If MenABCWY is administered in this way, a second dose of MenABCWY may be administered 6 months later to complete the series. \nThe footnote reads : \n*1) Healthy individuals aged 16– 23 years (routine schedule) when shared clinical \ndecision-making favors administration of MenB vaccination, 2) individuals aged 10 years \nand older at increased risk of meningococcal disease (e.g., due to persistent \ncomplement deficiencies, complement inhibitor use, or functional or anatomic asplenia) \ndue for both vaccines. \nDr. Talbot made a motion to make an amendment to postpone the vote for the pentavalent meningococcal disease vaccine until after re-evaluation of the currentmeningococcal guidelines as there are currently adequate vaccines to cover all of these \npathogens, and to reduce the complexity and the number of vaccines that need to be in a \nprovider’s office. Dr. Long seconded the motion. \n28 \n \n    \n  \n    \n  \n \n     \n \n \n  \n \n    \n  \n  \n \n      \n  \n \n  \n \n \n  \n  \n   \n  \n \n \n \n  \n \n   \n \n  \n \n \n \n \n \n  \n \n \n \n \n Dr. Long pointed out that the ACIP has a long history of difficulty in rescinding \nrecommendations, decreasing antigens , or decreasing vaccines. Perhaps looking at the entire \nschedule, they may decide that these vaccines , CWY versus B, should be separated by age \ngroup and indication. They already would change the architectural plan if they approve the \ncombination pentavalent vaccine. Then they would have to convey to people that there is something currently licensed and recommended in an odd way, but recommended, that would \nbe moot because most people would not receive these 2 vaccines at the same age or \nindication. If a bigger change is planned, the incremental change should not be made first. She \nalso pointed out that the proposed language would not be the narrowest indication for use of the pentavalent vaccine. The narrowest indication would be to use it only when both are \nrecommended and that would just be for the second dose of CYW. \nMs. Arthur (BIO) asked how long the delay would be before there would be a vote if the \namendment were to pass. She understood that the WG is considering some data and important \nissues pertaining to the adolescent schedule, which could mean no vote for this product for 12 \nto 15 months or more . \nDr. McNamara noted that if the intent was to table the vote on this question until after the new \nvotes on the adolescent meningococcal schedule, CDC discussed with the WG having that vote \nin February of 2025. Her default assumption would be that the pentavalent vote would occur at \nthat time as well. Obviously, nothing is set in stone. However, reassessing the schedule will take a significant amount of time. \nDr. Brooks said he did not feel that the ACIP could delay the vote and spoke against the \namendment. He recognized that the ACIP did not ask the manufacturer to make the vaccine as \nDr. Long pointed out, but they did, and he is grateful for it as Dr. Loehr said. The WG was \nstrongly in favor of PICO 1 and strongly against PICO 2. If there were concerns or questions, \nthe simple thing to do would be to vote against PICO 3 and choose Option A, PICO 1 (QPB) if \nboth are needed. That would be an incremental change that would not commit the ACIP to \nanything they did not want. He agreed that the ACIP has a history of making tough decisions , \nand this has grown tougher with every meeting. \nDr. Sanchez said he certainly understood that and wanted a revisit of the meningococcal \nschedule, at least in children. Knowing that will be in the distance and there is an FDA -approved \nvaccine is available, there are circumstances in which children will receive both vaccines, Q and \nB, it made sense to make it available under certain circumstances and under certain \nrecommendations, rather than tabling it for some future change. He suggested making the \nrecommendations without adding anything more to an already complicated schedule. Dr. Daley pointed out that Dr. Brooks was talking about the option on the screen, but his \nunderstanding is if we are in favor of what is on the screen, ACIP would need to vote down the \namendment and the first proposal both, and then someone would need to make a new motion for this.  \nDr. Lee agreed with Drs. Sanchez and Brooks that the ACIP needed to make a decision, and \nthat deferring that decision would not be helpful for frontline pediatricians and family \npractitioners. \nDr. Lee spoke in favor of Option A. \n29 \n \n  \n \n  \n  \n \n \n   \n \n \n  \n  \n    \n    \n     \n   \n   \n  \n      \n   \n \n \n \n  \n \n \n \n  \n \n \n \n \n \n \n \n \n \n  \n \n \n Vaccines for Children (VFC) Resolution \nDr. Jeanne Santoli (CDC/NCIRD) indicated that they prepared for the multiple options, which \nwould be reflected in her presentation of the VFC Resolution. She explained that the purpose of \nthis resolution was to update the resolution to add a new component to the VFC Resolution to \nreflect a newly available combination meningococcal vaccine that can be used to prevent meningococcal disease attributable to serogroups A ,C,W,Y and B, and to make minor updates \nto the existing components of the resolution (MenACWY component and MenB component). \nFor the MenACWY component, there are no proposed changes to the eligible groups. For the recommended vaccination schedule and intervals, there are 3 changes. The first would be to remove Menactra, which is no longer available as an option. The s econd would be to remove a \nfootnote that was used to add Menveo 1-vial to the VFC resolution when that vaccine was \nlicensed as an alternative product to the products that already were part of the resolution. No \nchanges were proposed for the recommended schedule, dosages, or contraindications and \nprecautions. For the meningococcal B component, the change to the eligible groups was to reference shared clinical decision-making because it was not referenced initially, and it is \nreferenced in the new proposed component. For consistency, that was added to the second \nbullet here under the eligible groups. A statement was added to the recommended vaccination \nschedule and intervals table that was missing from the original resolution to add a footnote \nmaking clear that MenB vaccines are not interchangeable by manufacturer. No changes would \nbe made to the recommended dosages or contraindications and precautions. \nPertaining to the upcoming vote on the combined pentavalent serogroup A,C,W,Y, and B \nvaccine, Dr. Santoli reviewed the eligible groups, recommended vaccination schedules and \nintervals for each Option A, Option B, and Option C that mirrored what the ACIP had been \ndiscussing. For Option A, there would not be a change to the eligible groups but there is a change in the second dose for children who are not at increased risk. This clearly indicates a monovalent, which was not the case for Option B. Otherwise, Options A and B were the same in \nthe resolution. Option C included additional changes to acknowledge the use of the combination \nvaccine when MenB alone is recommended. That also was reflected in the recommended vaccination schedule and intervals. \nNo changes were made to the standard statement indicating that when there is a published \nrecommendation, the information is incorporated by reference. Any c ontraindications and \nprecautions would be added prior to the VFC resolution being brought forward for a vote. \nDiscussion Points Recognizing that the final VFC vote would depend upon the final ACIP recommendation \nvote, Dr. Loehr moved to accept the VFC language as presented. Dr. Daley seconded the \nmotion. \nDr. Long said that after listening to her colleagues and understanding that there was not \nsupport for tabling the pentavalent vote, she wanted to withdraw her seconding on the \nmotion to table the vote. With no other seconds, this amendment did not pass. \nDr. Wharton clarified that with the second withdrawn pertaining to the amendment, there now was only one motion on the table for Option B as written. The amendment does not pass and ACIP returns to the original motion put forth by Dr. Loehr, which was Option B. Is any other discussion needed at this time? \n30 \n \n  \n \n \n \n \n \n \n \n  \n \n \n \n \n \n \n \n \n \n \n    \n  \n \n   \n \n   \n  \n    \n \n  \n \n \n \n \n  \n \n \n  \n \n \n \n  \n \n \n   Dr. Loehr asked if any colleagues wanted to do the amendment for Option A, now would be the time to do that. \nDr. Brooks asked if we would have to vote this motion down and have that option as a second \nmotion. \nDr. Lee said there are 2 options, Option B (the initial motion) and if anyone wanted to request an \namendment to the motion, essentially going to Option A, that is acceptable. Or you could vote \ndown this one and have another vote.For the sake of clarity, it would be easier to have all potential motions/votes on the table before moving to the voting section. She requested that \nOption B and Option A be displayed. \nOption B and then Option A were displayed. \nDr. Lee asked if anyone wished to make an amendment to vote for Option A. Dr. Daley made an amended motion to adopt the language for Option A as written. Dr. \nBrooks seconded the motion. \nDr. Lee clarified that Option A, the amendment, would be voted upon first. If that did not pass, \nthey would move to Option B. \nDr. Talbot pointed out that many of her colleagues were concerned about postponing this vote \nbecause physicians will be asking how to use this vaccine. While that is a legitimate concern, \nthe reality is that insurance will not cover the vaccine if the vote is postponed. It was not a question of how to use the vaccine, but whether patients would have to pay out-of-pocket. In terms of pediatricians calling with questions, there are 3 licensed vaccines that already are currently covered by insurance and the VFC. She emphasized that she did not think the ACIP \nshould make judgments based on other people’ s questions or how fast a pharmaceutical \ncompany wants to push a vaccine to market and instead thought that the ACIP should make \ndecisions based on what is the simplest and provides the best care for their patients. \nAs a reminder, public comment was presented prior to the votes. However, the votes were \ncombined in this proceedings document with their respective sessions for the purpose of \ncontinuity. \nVote: Meningococcal Vaccine \nDr. Jennifer Collins (CDC/NCIRD) recapped the votes on the table for Options A and B, which \nwere as follows: \nOption A (Amended Motion)\nPfizer’s MenABCWY vaccine may be used when both MenACWY and MenB are \nindicated at the same visit.* \nFootnote \n*1) Healthy individuals aged 16–23 years (routine schedule) when shared clinical decision-making favors administration of MenB vaccination, 2) individuals aged 10 years and older at increased risk of meningococcal disease (e.g., due to persistent complement deficiencies, complement inhibitor use, or functional or anatomic asplenia) due for both vaccines.  \nOption B (Initial Motion; only voted on if the amendment fails) \n31 \n \n  \n \n \n  \n \n \n \n \n \n \n \n  \n \n  \n   \n \n         \n          \n        \n \n \n \n  \n \n  \n \n \n \n  \n \n  \n  \n \n \n     \n  \n        \n        \n \n \n  Pfizer’s MenABCWY vaccine may be used when both MenACWY and MenB are indicated at the same visit. *If MenABCWY is administered in this way, a second dose of \nMenABCWY may be administered 6 months later to complete the series. \nFootnotes \n*1) Healthy individuals aged 16–23 years (routine schedule) when shared clinical decision-making favors administration of \nMenB vaccination, 2) individuals aged 10 years and older at increased risk of meningococcal disease (e.g., due to persistent complement deficiencies, complement inhibitor use, or functional or anatomic asplenia) due for both vaccines.  \nDr. Lee reminded everyone that the second for the motion to table the vote until a future time \ndid not pass, given that the second was rescinded and no other seconds were made. There was then a motion and a second to amend the vote on the floor to vote on Option A, which would be voted upon first. If that did not pass, they would move to Option B. If it did pass, there would not \nbe a vote on Option B. She asked ACIP members to put their cameras on. \nMotion/Vote #1: Option A Meningococcal Recommendation \nDr. Daley made an amended motion to adopt the language for Option A as written, which Dr. \nBrooks seconded. No COIs were declared. The motion carried with 10 affirmative votes, 4 \nnegative votes, and 0 abstentions. The disposition of the vote was as follows: \n10 Favored: Bahta, Bell, Brooks, Chen, Cineas, Daley, Kotton, Lee, Long, Sanchez \n4 Opposed: Loehr, McNally, Poehling, Talbot \n0 Abstained: N/A \nVote: Meningococcal VFC Resolution \nDr. Jeanne Santoli (CDC/NCIRD) recapped the VFC vote for meningococcal vaccines, which \nwill reflect that the ACIP voted to approve Option A that will be reflected in the VFC Resolution \naccordingly. \nMotion/Vote #1: Meningococcal VFC Resolution \nDr. Loehr moved to accept the VFC language as presented, which Daley seconded. No COIs \nwere declared. The motion carried with 14 affirmative votes, 0 negative votes, and 0 \nabstentions. The disposition of the vote was as follows: \n14 Favored: Bahta, Bell, Brooks, Chen, Cineas, Daley, Kotton, Lee, Loehr, Long, McNally, \nPoehling, Sanchez, Talbot \n0 Opposed: N/A \n0 Abstained: N/A \n32 \n \n  \n \n  \n \n \n  \n \n \n   \n    \n \n \n    \n  \n \n     \n \n \n \n \n \n \n   \n   \n     \n   \n  \n \n  \n   \n   \n \n   \n      \n     \n \n   \n    \n  \n \n  \n     \n    \n \n  \n   \n   Discussion Points \nDr. Poeling thanked everyone for the robust discussion about meningococcal vaccines. There \nhas been tremendous benefit from the vaccines that are being administered, and there is a lot \nmore to learn. She voted “no” to Option A because she wanted a broader recommendation, emphasizing that she r espected the votes of her colleagues and expected there would be many \nmore conversations to come about meningococcal vaccine. \nDr. Daley pointed out that one of the overarching goals of the entire program is to maximize \nprevention of vaccine-preventable disease, morbidity, and mortality. That is fundamental in the \ncontext of resource constraints and other constraints. Therefore, he would expect that the work \nof the Meningococcal WG would include evaluation of a MenB prevention strategy. The problem \nwas that this was not the direct questions under consideration during this session, so he wanted \nto highlight that distinction. In fact, conflating those two made it harder to make a decision. He \nthought they should foc us on the decision at hand, recognizing that there are compelling \nreasons to re-evaluate the current strategy for Men B, which is rare but severe. \nMs. McNally emphasized that while she favor s MenB vaccination and fewer injections , she also \nwas hoping for a broader recommendation. \nMPOX VACCINES \nIntroduction \nPablo Sanchez, MD (ACIP, WG Chair) provide an introduction and overview of the Mpox \nsession , reminding everyone that the global Mpox outbreak occurred in 2022 with the first case \nidentified in the United Kingdom (UK) in May 2022. It primarily affected gay, bisexual , and other \nmen who have sex with men (MSM). It was associated with person-to-person spread via close \nskin-to-skin contact, including sex. D eaths have occurred, primarily among persons with severe \nimmunocompromise from advanced HIV. US case counts and deaths comprised a third of the \ncases and deaths, with over 30,000 cases with 54 deaths. In terms of the current global cases , \nduring September 2023, the US has reported 30 to 99 cases. There are large number s of \ncases in Southeast Asia and Indonesia during this same time. \nAs a reminder, the JYNNEOS vaccine is comprised of a replication-deficient vaccinia virus , \nwhich is a live virus that is replication-deficient. It is administered subcutaneously via 2 vaccine \ndoses administered 28 days apart. Its effectiveness was assessed by comparing immunologic \nresponse to that for ACAM2000. It was licensed for prevention of both smallpox and Mpox, and \nit is currently recommended for persons with HIV and other immuno compromising conditions . \nJYNNEOS vaccine is licensed for persons ≥ 18 years of age. There is a current NIH trial \nunderway to evaluate the safety and immunogenicity for persons 12─ 17 years of age. \nThe outbreak recommendations were previously discussed during the February and June 2023 \nACIP meetings . In June 2023, the ACIP voted to recommend the 2-dose JYNNEOS vaccine \nseries for persons ≥ 18 years of age at risk of Mpox during an Mpox outbreak. P ublic health \nauthorities determine whether there is an M pox outbreak. A single case may be considered an \nMpox outbreak at the discretion of the public health authorities. The outbreak recommendations \nwere intended for any US Mpox outbreak regardless of whether it is associated with male-to-\nmale sexual contact. The clinical guidance, including use of the vaccine in children during \n33 \n \n   \n \n \n \n  \n \n  \n  \n \n    \n  \n     \n \n   \n  \n     \n   \n \n   \n    \n   \n   \n  \n  \n  \n  \n \n  \n   \n \n \n \n \n  \n   \n  \n \n  \n \n \n   \n   \n    \n \n \n  \n   \n \n \n    \n  \n \n \n \n \n \n \n \n \n  \n \n \n \n \n outbreaks , were discussed as well. The national Mpox vaccination strategy for pre-exposure \nvaccination during the current outbreak includes the following individuals :5 \n• Gay, bisexual, and other MSM, transgender or non-binary people (including \nadolescents who fall into the forementioned categories) who in the past 6 months \nhave had: \n− New diagnosis of ≥1 sexually transmitted disease \n− More than one sex partner \n• People with the following in the last 6 months : \n− Sex at a commercial sex venue \n− Sex in association with large public events in geographic areas where Mpox \ntransmission is occurring \n• Sexual partners of people with the above risks \n• People who anticipate experiencing above risks \n• People with HIV or other causes of immunosuppression who have had recent or \nanticipate potential Mpox exposure \nThe World Health Organization (WHO) is embarking on the development of an elimination \nprogram of human-to-human transmission of Mpox. Certainly , additional resources and data are \nneeded. Immunization will be one component of the strategy for worldwide elimination of Mpox \ndisease. Elimination is a complex issue that has not been addressed by the WG . However, a \nrecommendation that persons at risk for M pox during the ongoing outbreak receiving the \nvaccines, if they have not already, may support any upcoming strategy from the WHO with \nrespect to future elimination of M pox. Dr. Sanchez indicated that the interim routine \nrecommendation to be proposed for a vote during this session would read as follows: \nACIP recommends vaccination* with the 2-dose† JYNNEOS vaccine series for persons \naged 18 years and older at risk for Mpox§ \n*Interim recommendation that ACIP will revisit in 2-3 years \n†Dose 2 administered 28 days after dose 1 \n§Persons at risk: \n• Gay, bisexual, and other men who have sex with men, transgender or nonbinary people who in the past 6 months have had one of the following: \n− A new diagnosis of ≥ 1 sexually transmitted disease \n− More than one sex partner \n− Sex at a commercial sex venue \n− Sex in association with a large public event in a geographic area where mpox transmission is occurring \n• Sexual partners of persons with the risks described in above \n• Persons who anticipate experiencing any of the above \nThe potential implications of an interim routine recommendation are that it would increase \nvaccine coverage and prevent or minimize future outbreaks, and remove some stigma and \nfacilitate one-to-one consultation with clinicians during their appointments for vaccination. It also \nheralds the potential commercialization of the JYNNEOS vaccine. The product sponsor, Bavarian Nordic, has indicated that they will attempt to commercialize the vaccine if it is on a \nroutine schedule. This would transition the vaccine from US government stockpiles, which were intended for smallpox preparedness , to the commercial sector. \n5 https://www.cdc.gov/poxvirus/monkeypox/interim-considerations/overview.htm \n34 \n \n  \n \n    \n  \n \n  \n   \n   \n \n \n  \n \n  \n \n   \n  \n \n \n  \n         \n     \n  \n \n     \n  \n   \n    \n   \n \n  \n  \n  \n    \n   \n  \n \n  \n   \n \n \n \n  \n \n   \n    \n  Regarding the tentative timeline for ACIP discussions and votes, this meeting would result in \ninterim routine recommendations if the ACIP adopts the recommendation and clinical guidance. \nPublication is planned for 2 Morbidity and Mortality Weekly Reports (MMWRs) in 2024, \nincluding: 1) Use of the JYNNEOS vaccine during M pox outbreaks; and 2) Use of the \nJYNNEOS vaccine among persons at risk during the ongoing Mpox outbreak. Potentially in \n2024, the ACIP would consider the results from an ongoing NIH trial on the use of the JYNNEOS vaccine in adolescents 12─ 17 years of age. The epidemiology, cost-effectiveness \nanalysis, and other data would be reviewed in 2 to 3 years to determine whether a routine \nrecommendation should be continued. \nUpdates about US Mpox Epidemiology, Vaccine Safety, and Vaccine Effectiveness \nFaisal Syed Minhaj, PharmD, MPH, DABAT (CDC/NCEZID) provided updates on US \nepidemiology, vaccine safety, and vaccine effectiveness (VE). Beginning with situational awareness and updates in terms of Mpox case counts from the beginning of the outbreak in \nMay 2022 through September 28, 2023,\n6 the peak of M pox cases occurred during August 2022 \nand cases have decreased substantially in 2023. Taking a closer look at the numbers in 2023, \nthe case counts from the beginning of the year to September 28, 2023 did not reach zero at any \npoint. During the month of January, the 7-day average case range was generally between 5 and \n7 cases per day. Cases decreased in February down to 1 to 3 cases per day. However, they \nrose again in the summer months up to 5 cases per day. From July through now, there is still an \naverage of one to four cases per day. Cases have not been consistently below this level, \nhighlighting that Mpox has not been eliminated from the U S. Looking at the cases in 2023 \ngeographically, cases are occurring across the US in different jurisdictions. C ases are spread \nout and many are not linked to other known cases, which suggests continued community \ntransmission or potential underdiagnosis. D uring the height of the outbreak in Summer 2022 \nwhen clinician awareness was high and vaccine campaigns were occurring, the rate of undiagnosed Mpox was likely low at around 1% in the MSM population. Seeing unlinked cases \ncurrently across jurisdictions suggests additional ongoing transmission. \nCases have been seen in patients following vaccination. This has been reported since the \noutbreak started, including some clusters. However, it is relatively rare in comparison to the total \ncase counts. Importantly, most patients with infection following vaccination have mild illness . \nData from a recently published manuscript on infections following vaccination\n7 show that the \nmedian number of lesions in these patients was 2, with an interquartile range of 1 to 5. \nAdditionally, only 2 out of 30 patients received tecovirimat and few were hospitalized, \nsuggesting that illness was mild following vaccination. \nReinfection of Mpox is rare and was not well -reported until the current outbreak. Potential \nreinfection cases have been published in the literature, but only a few with convincing evidence \nof true reinfection. In a recently published case series ,8 the authors found a total of 8 probable \ncases of reinfection. Reinfection appears to be mild with a lower lesion count and duration of \nrash. CDC is aware of less than 10 cases of probable reinfection, which makes up less than \n0.001% of cases. \n6 https://www.cdc.gov/poxvirus/mpox/response/2022/mpx-trends.html \n7 Hazra A. Lancet Infect Dis. 2023 Sep 4:S1473-3099(23)00492-9 \n8 Hazra A. Lancet Infect Dis. 2023 Sep 4:S1473-3099(23)00492-9 \n35 \n \n     \n    \n  \n \n  \n   \n      \n \n \n  \n   \n \n \n    \n  \n     \n \n   \n   \n  \n   \n   \n   \n \n   \n  \n  \n \n \n \n \n   \n  \n    \n \n \n  \n     \n \n \n \n  \n  \n \n  \n  \n \n   \n   \n   CDC’ s mpox c linical consult service was created early in the outbreak to discuss any Mpox \ncase s and transitioned to be a resource for treatment and guidance on managing severe M pox \ncases. The consultation service is the only way to access most medical countermeasures \navailable for severe M pox. These consultations include some new cases, but many are \nrepeated consultations on infections that began months ago and require numerous courses of \navailable medical countermeasures. From the beginning of the outbreak to now , 54 people have \ndied in the US, with another 2 in September 2023. As CDC published in 2022,9 people with \nsevere Mpox and deaths share the same equity disparities seen between cases and \nvaccination. Black persons make up the majority of severe cases . Most severe cases often have \nadvanced HIV or AIDS, are not on antiretrovirals at diagnosis, are not linked to care, many are \nexperiencing homelessness , and importantly are not vaccinated with JYNNEOS. \nIn terms of demographics, the gender and age distributions of M pox cases have not changed \nsince the June 2023 ACIP presentation. Most cases are among cisgendered males , highlighting \nthe population for which JYNNEOS vaccination is recommended. The race and ethnicity of reported cases also remains similar to what was reported in June. Early in the outbreak, greater \nthan 40% of cases were detected in White persons, but during the peak of 2022, Black and \nHispanic persons were most affected. Recently , there have been cases across different racial \nand ethnic groups, but with large proportions of cases among Black and Hispanic persons \nthroughout the outbreak ;\n10 Achieving vaccine equity is needed to address this disparity. \nGlobally, there is a different trend of cases than in North America. Between April through \nSeptember 2023, there have been large increases in Southeast Asian and Western Pacific \nregions. Over the past month, the European region also had one of its largest relative increases \nfrom August to September. Many recent increases were from countries in East and Southeast \nAsia based on detections from September 4 through September 24, 2023.11 These are not the \nonly countries in this region experiencing an increase in cases. Earlier in the week, there were \nnews reports of new cases detected in Vietnam and Indonesia. When examining cases globally, \nit is important to recognize that robust M pox surveillance systems and vaccine implementation \nprograms seldom exist outside of Europe, Canada, and the U S. \nVaccine uptake slowed dramatically following the peak of the outbreak in July through \nSeptember 2022. Since the beginning of the outbreak in May 2022, first dose vaccine coverage \nis 38.8% and second dose coverage is 24.3% among the estimated at-risk people who are \neligible for vaccination. Those at risk for M pox are defined as HIV-positive and pre- exposure \nprophylaxis ( PrEP)-eligible individuals totaling an estimated 2 million persons in the US. An \nincredible effort was put forth into achieving over 1.3 million doses administered. However, there is room for improvement. Ninety -three percent of doses were administered in 2022, and \nalthough there was a shift from first to second doses in 2023, second dose coverage remains below 1 in 4 and 37 of 54 jurisdictions are still below these national coverage estimates, \nemphasizing the work needed to get at-risk people primary vaccination. Moving forward, a \nyounger unvaccinated population also will age into those eligible for primary vaccination. \nThere also has been a shift in vaccine administration sites from public health clinics to medical \ncenters. Public health providers administered 40% of all vaccines through March 2023. Medical \ncare providers administered an increasing proportion of vaccines since the start of the outbreak, and pharmacies consistently provided 3% to 4% of all vaccines. Looking closer at the types of \nmedical center providers giving vaccine, there were statistically significant increases in vaccines \n9 https://www.cdc.gov/mmwr/volumes/71/wr/mm7144e1.htm \n10 https://www.cdc.gov/poxvirus/mpox/response/2022/demographics.html \n11 https://worldhealthorg.shinyapps.io/mpx_global/ \n36 \n \n      \n \n \n    \n \n      \n  \n \n    \n \n    \n   \n   \n      \n    \n  \n \n  \n   \n  \n  \n    \n   \n    \n      \n   \n  \n   \n  \n  \n      \n \n \n   \n        \n     \n      \n      \n \n \n \n    \n    \n   \n \n  \n \n \n \n  provided by primary care offices, F ederally Qualifying Health Centers (FHQCs) , and other \nhealth centers. \nNow to discuss a few models12 relate d to vaccination in the current outbreak and why \nvaccination is an important strategy to prevent ongoing cases. Based on the results from a \nmodel of M pox transmission in Washington, DC in which the model estimated cases averted by \nbehavioral adaptation, vaccination, or both interventions , surveys indicate that individuals \nreduced the number of sexual partners in response to M pox. This scenario does not include \nvaccine administration. The model estimates that behavioral adaptation alone could have quickly flattened the curve, but not ended the outbreak within 1 year. Based on vaccine \nadministration records in DC, not including behavioral adaptation, the model indicates that \nvaccination would have taken longer to have an effect than behavioral adaptation, but would \nhave ended the outbreak within a year. Based on the model estimates of prevalent infections \nwith vaccination and behavioral adaptation combined, the model estimate d that combined, \nthese 2 interventions averted 80% of potential Mpox cases in DC , with behavioral adaptations \nbeing key to averting cases early on and vaccination being key to ending the outbreak. Similar \nresults also were found in models in other cities. \nModels not only estimate that vaccination is key to ending the M pox outbreak, but also that \nvaccination is key to preventing Mpox resurgence.\n13 Later in the outbreak in DC, the model \nestimated that nearly the entire high- risk population of MSM who engages in 1-time sexual \npartnerships gained full or partial immunity through vaccination or through acquiring and \nrecovering from Mpox making resurgence in DC unlikely. However, over time, population level \nimmunity will decrease due to population turnover. Further, most US jurisdictions had a lower vaccine coverage than DC , potentially leaving them vulnerable to resurgence. For the purposes \nof this model, either 1- or 2-dose vaccination was used. It is known from VE data that 2 doses is \ngreater protection. In this model, they defined a resurgent outbreak as continuous community \ntransmission for at least 3 months, the risk of recurrence decreases linearly as population level \nimmunity increases. While the probability of recurrence decreases linearly with population level immunity, the size of potential outbreaks has a more complex relationship with population level \nimmunity. The model estimates that resurgent outbreaks will be very small if the population level \nimmunity is greater than 50%. Currently, only 7 jurisdictions are above 50% with at least 1 dose \nof JYNNEOS coverage among the high-risk population. \nIn terms of the VE and safety updates. These data were presented during previous ACIP \nmeetings. To summarizes the available VE data from 3 separate studies in the US (1 from Epic \nCosmos, 1 from a multi -jurisdictional case-control, and 1 from New York State), 1-dose VE \nranged from 36% to 75%. VE ranged for from 66% to 89% for 2-dose vaccination. Consistently \nacross the studies, VE for 2-dose vaccination was higher than 1 dose, emphasizing the \nimportance of finishing the 2-dose series. \nTo update VE estimates from the multi -jurisdictional case-control study that was performed in 12 \nUS jurisdictions and initially presented during the February 2023 ACIP meeting. The population \nis MSM 18-49 years of age and the time period is August 19, 2022 through September 27, \n2023. Cases were identified from a jurisdiction’ s list of Mpox cases, while controls were \nidentified from healthcare settings providing HIV P rEP or sexually transmitted infection ( STI) \nclinics. VE was adjusted for age, race, ethnicity , and immunocompromising conditions. It was \n12 ttps://www.medrxiv.org/content/10.1101/2023.02.10.23285772v1.full.pdf Lines  and shaded regions reflect median and \ninterquartile range from 120 simul \n13 Pollock ED. MMWR Morb Mortal Wkly Rep 2023;72:568–573 \n37 \n \n     \n    \n \n       \n  \n \n \n \n    \n \n       \n \n  \n  \n   \n  \n  \n \n   \n  \n   \n  \n  \n  \n  \n \n  \n  \n  \n  \n  \n \n \n \n \n \n    \n   \n   \n  \n  \n \n \n \n    \n       \n     \n    \n \n stratified by route of administration and immunocompromise status. Overall VE from partial or 1-\ndose vaccination was updated to 73% (59-82), with similar results for those with either \nadministration route. This estimate is similar to the previously reported 75%, but does have a \nsmaller confidence interval. Overall, VE from 2-dose vaccination was updated to 83% (71-90), \nwith similar results with either administration route. These updated data suggest that the VE estimates are stable. \nLooking at the updated VE estimates for self-reported immunocompromised individuals, the \nconfidence intervals of the estimates no longer cross zero. However, it is important to note that \nthe sample sizes are still small within this subset of individuals and have wide confidence \nintervals that range from 8-91 for 1 dose and 23- 96 for 2 doses . The point estimates of self-\nreported immunocompromised status appear similar but non-significantly lower than that in self-\nreported immunocompetent individuals. Notably, as immunocompromised status was self-\nreported, it is hard to ascertain the accuracy of this measurement for those who are truly \nimmunocompromised. For example, people living with well -controlled HIV with CD4 counts \nabove 350 may have responded that they are immunocompromised. Overall, this data, albeit \nencouraging , needs to be interpreted carefully. Ultimately, more work needs to be dedicated to \nunderstanding what VE is in immunocompromised people. \nCDC continues to monitor AEs after JYNNEOS using 2 surveillance systems, the Vaccine \nAdverse Event Reporting System (VAERS) and the Vaccine Safety Datalink (VSD). V -safe data \ncollection for Mpox vaccines was available from November 2022 to March 21, 2023. \nApproximately 90% of the reports were submitted during the calendar year 2022. There has \nbeen a relatively small amount of additional safety data accrued during 2023, but no new safety \nsignals have been identified and no changes have been observed since th e previous ACIP \npresentations in February and June 2022. The AEs most commonly reported to VAERS have \nbeen injection site symptoms such as redness, swelling, pain, and itching. Myocarditis and \npericarditis are adverse events of special interest (AESI) and observed rates are consistent with \nthe expected background rates. VAERS and VSD do not suggest an increased risk for \nmyocarditis or pericarditis following JYNNEOS vaccination, but the possibility of a small risk \ncannot be excluded. The frequencies of local and systemic reactions reported to V -safe after \nMpox vaccine were similar to those report in clinical trials. No new or unexpected safety \nconcerns have been identified. \nIn summary, M pox cases and deaths continue to be reported domestically and globally, but no \nlonger at the same levels observed during 2022. There was an incredible effort and robust \nvaccine response, but there is still room for improvement. Less than a quarter of the eligible \npopulation is fully vaccinated with 2 doses. It is important to remember that with little vaccine \nimplementation outside the US, Canada, or Europe and with a rise in cases in Asia and other \nregions, the outbreak is continuing. Modeling data suggest that without vaccination, \ntransmission of Mpox will continue with sporadic outbreaks. No new safety signals have been \nidentified from VAERS or VSD and VE appears stable for immunocompetent people. \nDiscussion Points \nDr. Poehling said she very much appreciated the data using multiple studies to demonstrate that \nboth doses of JYNNEOS are important for VE. She also highlighted that according to uptake, it \nappeared that about 63% of the population who start the JYNNEOS series actually finish both \ndoses , which is very important. She asked whether there are data on the 8 cases of reinfection, \nwhich is extraordinarily low and they seem to be very mild, in terms of whether they received 1 \nor 2 doses. \n38 \n \n  \n   \n \n    \n \n \n   \n  \n \n     \n \n \n     \n   \n  \n  \n      \n     \n \n  \n \n   \n \n \n    \n  \n \n  \n  \n \n \n \n \n  \n \n     \n   \n     \n \n \n   \n  \n   \n  \n   \n \n     \n  \n   Dr. Minhaj said that in that global case series , 1 individual was vaccinated during that time \nperiod, and there are cases following reinfection that CDC is currently investigating, some of \nwhom were vaccinated between their first and second infection. However, the number is small \nand interpretation of this data can be challenging. \nMs. Bahta asked whether the cases that followed vaccination had been analyzed for method of \nvaccine administration. \nDr. Minhaj indicated that they are looking into this, but from VE data is that there does not seem \nto be a difference in VE from either administration route. \nDr. Rao added that they have looked to see if there was any pattern. For example, a cluster of \ncases occurred in Chicago in May that affected people who were fully vaccinated, and there \ndoes not seem to be an association with those breakthrough infections and the route of \nadministration. There were breakthrough infections among people who received 2 doses \nintradermal ly (ID) , 2 doses subcutaneous ly (SQ), and 1 dose SQ and 1 dose ID . Fewer received \n2 doses ID that were breakthrough cases from that cluster. The national data mirrors this . \nDr. Guagliardo added that they have looked at the national case surveillance data and also \nassessed the route of administration amongst these breakthrough infections and have not seen \nany differences in severity between routes of administration. They are working on publishing \nthat. \nMs. Bahta noted that her biggest concern was about the complexity of ID vaccination and how \nthat might have impacted effectiveness, but it sounded like no patterns have been observed. \nDr. Kotton requested additional information about any studies underway looking at \nimmunocompromised people and, if so, what the timeframe is for getting that information. This \npopulation was devastated by this and were among the deaths reported. Many of them were \nimmunocompromised and from underserved and other populations. \nDr. Rao confirmed that the deaths are predominantly occurring among people who have \nadvanced HIV or some other form of severe immunocompromise. These also are individuals \nwho did not receive any doses of the vaccine. The VE estimates are problematic because a true \nVE estimate cannot be extrapolated among immunocompromised people. They also do not \nknow VE for individuals with that degree of severe immunocompromise. They do recognize this \nas an absolute priority. In the multi -jurisdictional study, they are going to attempt to understand \nthe CD4 counts and viral loads for those patients in order to determine whether they were truly \nimmunocompromised. \nDr. McCollum added that through the multi -jurisdictional study and the case-control set up for \nmonitoring of VE , there are opportunities for monitoring. It will be a relatively small subset of \nthose with well -defined immunocompromise or self-reported immunocompromise. They also are \nactively engaged in collaborating on a longitudinal study out of the University of California Los \nAngeles (UCLA ) to assess individuals presenting to and receiving care from HIV and sexual \nhealth clinics in the area and monitor them longer -term for self-reported and clinically defined \nhealth events and some of the defined risk factors. That also involve s blood collection for \nserology , which will provide a nice additional laboratory component. They also have been \ntalking to potential collaborators outside of the US to look at populations in endemic regions to \nensure that they are thinking broadly about the scope of data that could be collected. This is an \n39 \n \n    \n \n \n \n  \n \n \n \n  \n  \n \n    \n  \n \n   \n   \n   \n  \n \n \n  \n    \n \n \n    \n   \n   \n   \n   \n      \n \n  \n \n \n  \n \n \n   \n \n   \n \n \n   \n \n \n \n ongoing story and a top priority to better understand the impact and potential necessity for \nvaccine use in these populations. \nDr. Kotton emphasized the importance of assessing people with advanced HIV. She also \nencouraged CDC to look outside of that population, given that an estimated 3% of the US \npopulation is immunocompromised. \nIn terms of the recommendation, Dr. Middleman (SAHM) emphasized the importance of getting \nthis vaccine into the right people. Gender identity and sexual attraction descriptions do not \nnecessarily translate into behaviors. In reading the recommendation and in terms of the \nepidemiology, her understanding was that it is the behavior that puts people at risk (e.g., \nreceptive anal intercourse and anal intercourse in general ). The first line of the recommendation \nis confusing and will confuse a lot of people because it is really mixing gender identity \nterminology with sexual attraction terminology, which does not translate into behavior. She thought it would be helpful if the recommendations actually stated the risk behavior. She did not believe a transgender male, unless they are engaging in receptive intercourse (e.g., someone \nassigned female at birth who is now a trans gender male ) would be in the risk category unless \nshe was reading that incorrectly. While she understood why it is difficult, she also thought they \nshould identify the behaviors that put people at risk in order to protect everyone who requires protection. \nDr. Fryhofer (AMA) said that while the safety information was very reassuring, there previously \nwas a contraindication on giving this vaccine with COVID vaccines. She requested additional \ninformation on this and how they came to that decision. \nDr. Rao clarified that it is not a contraindication or precaution. This is co-administration guidance \nthat is included in the CDC COVID-19 Interim Clinical C onsiderations and the Interim Clinical \nConsiderations for the Mpox vaccine. They want to note that it is something people might keep \nin mind until there are data that can absolutely rule out even the smallest chance of myocarditis \nbeing potentiated after COVID -19 and JYNNEOS vaccine s are given together. There have not \nbeen any safety signals to suggest that the JYNNEOS vaccine is associated with \nmyopericarditis . With ACAM2000, the other orthopoxvirus vaccines, there is a definite signal for \nwhich the mechanism is not understood. Therefore, this guidance was included for JYNNEOS. \nWhile the data thus far do not support that, it is not possible to rule out the very smallest chance at this time. She noted that she would discuss this further in her last presentation of this \nsession, and that CDC STD experts also were involved in the development of this language, so perhaps one of them could speak during the discussion session about exactly why this specific wording was chosen. It is identical to the wording that has been used throughout this particular outbreak response. \nEtR F ramework for the JYNNEOS Vaccine \nAgam Rao, MD (CDC/NCEZID; CAPT, US Public Health Service) presented the EtR \nFramework for vaccination with JYNNEOS vaccine for persons at risk of Mpox. She reminded \neveryone that the EtR Framework is a structure to describe information considered in moving from evidence to ACIP vaccine recommendations. It provides transparency around the impact of \nadditional factors on deliberations when considering a recommendation. For this EtR analysis, \nthe WG’s question was: \nDoes ACIP recommend vaccination with the 2-dose* JYNNEOS vaccine series for \npersons aged 18 years and older at risk† for mpox? \n40 \n \n  \n  \n \n   \n  \n  \n  \n  \n    \n \n   \n   \n \n \n \n    \n       \n \n  \n \n \n  \n \n   \n  \n  \n   \n   \n   \n  \n    \n  \n  \n \n  \n   \n     \n       \n    \n    \n    \n   \n  \n \n  \n   \n      \n  \n  \n  \n \n  \n  *Dose 2 administered 28 days after dose 1 \n• Gay, bisexual, and other MSM, transgender or non-binary people who in the past 6 \nmonths have had one of the following: \n− A new diagnosis of ≥1 sexually transmitted disease \n− More than one sex partner \n− Sex at a commercial sex venue \n− Sex in association with a large public event in geographic areas where Mpox \ntransmission is occurring \n• Sexual partners of persons with the risks described above \n• Persons who anticipate experiencing any of the above \nThe rationale for the age selection for the EtR Framework is that the JYNNEOS vaccine is \ncurrently licensed for persons 18 years and older. There is an NIH trial underway to study the safety and immunogenicity of JYNNEOS among persons 12 ─17 years of age. When those data \nare available, the WG will review them and possibly bring this back to the ACIP. The comparator \nis no vaccination, so when going through the EtR domains, the comparison will be the \nvaccination versus no vaccination. The outcomes are prevention of disease, severity of disease , \nSAEs, and m yocarditis/pericarditis . As a reminder, the EtR domains include the public health \nproblem, benefits and harms, values, acceptability, equity, feasibility, and resource use. Dr. Rao \npresented the WG’s interpretation of the data for each of these domains and the response to the \nquestions for each. \nBeginning with the public health problem , Mpox cases continue to occur domestically and \ninternationally, including in clusters, but also in cases that cannot be connected to clusters. \nSevere disease and deaths continue to occur as well. Over 1.25 million doses of JYNNEOS \nvaccine have been administered in the US, which is great. While it took a lot of effort for that to \nhappen, national vaccine coverage remains lower than ideal . This is possibly because of the \nlower perceived risk of Mpox in the last 6 months. CDC modeling data suggest that larger \noutbreaks may occur if vaccine coverage remains less than 50% nationally for persons at risk for M pox. Coverage is currently only about 23% to 24%, so 1 in 4 people who should be \nvaccinated are vaccinated at this time. To reiterate, severe disease and deaths are continuing to \noccur in predominantly unvaccinated people. \nMoving to benefits and harms, there are 3 main sources of VE data, including the CDC Epic \nstudy, the CDC multi -jurisdictional study, and a New York State study. The methodology of \nthese studies and the data from them were presented during the 2 previous ACIP meetings and \nearlier in Dr. Minhaj ’s presentation. To recap, 2 doses of the JYNNEOS series were found to be \nbetter than 1 dose. The estimated VE for preventing Mpox disease is 66% to 89% for the 2-dose \nvaccine series. The CDC multi -jurisdictional study continues to collect data. To CDC’s \nknowledge, it is perhaps the only source of data that will be continued worldwide. CDC is \nattempting to estimate the VE in preventing infections among immunocompetent versus \nimmunocompromised persons, and recognizes that this is a major gap in understanding. \nThe ACIP previously recommended use of the 2- dose JYNNEOS vaccine series for 2 \npopulations, including populations at increased risk of occupational exposure to orthopoxviruses \nand persons at risk for Mpox during Mpox outbreaks. At that time, ACIP reviewed the GRADE \ndata and the available VE data. Subsequent data support its effectiveness for the population \nimpacted by the ongoing outbreak . The WG determined the desirable anticipated effects to be \n41 \n \n   \n   \n   \n \n    \n \n \n  \n  \n   \n   \n    \n \n    \n  \n   \n    \n \n \n   \n  \n  \n  \n  \n \n  \n  \n \n   \n  \n \n    \n  \n  \n     \n \n      \n   \n    \n     \n    \n  \n \n   \n   \n   \n  \n  \n  \n  large. Similarly, there have been no new safety concerns since the previous ACIP votes about \nthe use of JYNNEOS. The AEs most commonly reported to VAERS have been injection site \nsymptoms such as redness, swelling, pain, and itching. The WG interpreted these as being \nsmall undesirable anticipated effects. Because the desirable anticipated effects are large and \nthe undesirable anticipated effects are small, the WG felt that the intervention of vaccination \nwith JYNNEOS compared to no vaccination is favored. \nIn terms of the values domain, early in the Mpox outbreak response, multiple national surveys \nindicated that there was strong interest in the JYNNEOS vaccine. These data were presented in \ndetail during the February 2022 ACIP meeting. To summarize the data, during August to \nNovember 2022, greater than 85% of respondents in the American T ransformative HIV Study \n(AMETHST)14 were interested in the vaccine. D uring August to December 2022, 50% of Porter \nNovelli survey responders who identified as LGBTQ+ felt the vaccination was important to \nprotect them from Mpox .15 During October to November 2022, greater than 70% of MSM in a \nSan Francisco survey of persons experiencing homelessness reported that they would accept \nor have accepted the vaccine.16 During October to December 2022, an American Men's Interest \nSurvey (AMIS ) showed that those who were concerned about Mpox were 3.5 times more likely \nto be vaccinated.17 In addition to this information, other information also was obtained. \nEarly in the outbreak , not surprisingly, persons seeking vaccination were supportive of the \nJYNNEOS vaccine . One of those study surveys was performed during a study called the DC \nPET++ Study,18 which is a CDC and DC Health c ollaboration to follow a cohort of persons at \nelevated risk of Mpox exposure in Washington DC who presented for vaccination between \nAugust 2022 through October 2022. This survey of 866  adults found that greater than 85% \nagreed or strongly agreed that vaccines for Mpox should be available to anyone who wants the \nvaccine , and 82% said that they were likely or very likely to get a third dose if it was to be \nrecommended; however to be clear, a third dose is not recommended. Another evaluation in \nWashington, DC around the same time period supported the same idea. \nAlso early in the response, studies show ed that there were some conflicting feelings among the \npeople who are recommended to be vaccinated. A survey was performed by Curtis et al . among \n320 persons,19 primarily MSM living in Illinois and at risk for Mpox. Among the respondents , \n24.1% had received 2 vaccine doses, 27.5% had received 1 dose, and 47.5% had received no \ndoses. Persons who were vaccinated were more likely to have higher education, known \nsomeone with Mpox , expressed concern about their safety, and be less likely to report recent \nfood insecurity. The Turpin et al. study20 also evaluated this in qualitative interviews performed \nwith 24 Black MSM attending HIV prevention-related activities in the greater DC area, which is a \nvery important population. This was early in the Mpox response in May 2022. At that time, there \nwas not as much availability of the Mpox vaccine as there is now. While there is now sufficient \nvaccine to vaccinate all of the people SQ who are recommended to receive the vaccine, a \ncommon concern at that time was the lack of availability of the Mpox vaccine, which implies \ninterest in the vaccine. Vaccine hesitancy also was expressed commonly , but possibly was \nsimilar to vaccine hesitancy reported for other vaccines. \n14 https://grants.nih.gov/grants/guide/rfa-files/RFA- AI-21-018.html \n15 https://emoryamis.org/wp-content/uploads/2022/08/2022-Monkeypox-Survey.pdf \n16 https://www.cdc.gov/mmwr/volumes/71/wr/mm7135e1.htm \n17 Filardo TD. Vaccine. 2023 Sep 7;41(39):5673-5677 \n18 Hassan, R. (in press). Sexually Transmitted Diseases \n19 https://pubmed.ncbi.nlm.nih.gov/37236817/ \n20 https://pubmed.ncbi.nlm.nih.gov/37510557/ \n42 \n \n  \n  \n    \n    \n     \n    \n  \n   \n   \n  \n \n \n \n \n    \n  \n  \n   \n     \n   \n    \n   \n \n \n \n    \n  \n \n     \n \n   \n \n  \n      \n     \n \n \n  \n    \n    \n       \n   \n     \n \n \n   \n   Moving to more recent data, CDC issued a “CDC’s S tate of Vaccine Confidence Insights \nReport” in June 2023.21 A month prior to issuing that report in May 2023, an Mpox cluster was \nidentified in Chicago that predominantly affected people who received 2 doses of the JYNNEOS \nvaccine. This report was intended to review Mpox -related discussions on 23 news and social \nmedia outlets in the Chicago area in order to understand the sentiments of the affected \npopulation and develop communication material accordingly. Mpox vaccine hesitancy among \nthe general public and LGBTQ -affiliated groups was noted. People questioned the effectiveness \nand safety of the vaccine and expressed distrust in national reporting. However, when 18 \npatients who were impacted by that outbr eak were interviewed, 18 agreed to an interview . \nAmong them were patients who were fully vaccinated, partially vaccinated, and unvaccinated. \nMost vaccinated persons felt that the vaccine was effective in reducing severity and some assumed it would prevent infection. Most stated that they would recommend the vaccine to \nothers . Unvaccinated persons reported initial interest in the vaccine when the supply was limited \nand they were unable to receive it. T hey reported they did not seek it again because case \ncounts decreased so they assumed diminished risk . \nIn June 2023, CDC performed an online focus group with 52 people to help develop CDC \ncommunication material. Participants were included if they identified as men (including \ntransgender men and transgender women), were unvaccinated for Mpox, were never diagnosed \nwith Mpox , were 18─ 45 years of age, and had sex with 2 or more men within the past 6 months. \nThis essentially was people who were eligible for the Mpox vaccine. The participants were \nintentionally of diverse racial and ethnic backgrounds . They were shown various communication \nmaterials developed by the CDC. Exposure to the information about Mpox vaccine safety and \neffectiveness and hearing that there is a current threat of Mpox increased their interest in \nreceiving Mpox vaccine information. Although some of the individuals participated in this focus \ngroup who were not interested in the vaccine or were ambivalent about the vaccine, that \nchanged after seeing the materials. Many who were disinterested in the vaccine became \ninterested and said that the current risk of Mpox and protecting their community were \nmotivating. \nTo summarize the values domain data, vaccine demand was high early in the outbreak \nresponse when case counts were high. National surveys and interviews early and later in the \noutbreak indicated that there is overall interest in JYNNEOS vaccinations, but as with any \nvaccine, some people experience vaccine hesitancy. In response to whether the target \npopulation feels that the desirable effects were large relative to the undesirable effects, the WG \nanswered “probably yes. ” Because interest and intent to get vaccinated varied among the \naffected population and a perceived lower risk of Mpox may be contributing to reduced interest \nin the vaccine, the WG felt that there was possibly “important uncertainty or variability” in how \nmuch people value the main outcomes. \nMoving to the acceptability domain, health departments are supportive of and requested a lot of \nthe JYNNEOS vaccine and organized vaccination campaigns. An online survey\n22 early on \nshowed that clinicians during July, August, and September 2022 were interested in getting their \npatients vaccinated and 69% felt that the US did not have enough Mpox vaccines to handle the \noutbreak at that point. A few weeks later on September 12, 2022, a survey showed that 66% \nhad treated at least 1 Mpox patient, 76% knew where a patient could get the JYNNEOS \nvaccine, and 86% wanted to be able to provide the vaccine in their offices. \n21 https://www.cdc.gov/vaccines/covid-19/downloads/SoVC- MPOX -062723.pdf \n22 https://app.sermo.com/barometer/unitedstates \n43 \n \n  \n \n    \n  \n    \n    \n \n \n    \n   \n \n     \n \n    \n   \n   \n  \n   \n \n \n    \n  \n    \n  \n   \n   \n  \n       \n \n  \n  \n \n \n  \n  \n    \n  \n    \n \n \n  \n     \n  \n   \n   \n   \n More recent data come from a Porter Novelli survey of pediatricians and family practice \npractitioners with approximately 100 people in each group performed in August 2023. The \nsurvey included 3 Mpox vaccine questions added to a survey on pediatric COVID -19 vaccine \nattitudes and behaviors. The responders included family practitioners ( 85%) and pediatricians \n(88%) who cared for children 12─ 17 years of age and family practitioners ( 70%) and \npediatricians (60% ) who cared for patients ≥18 years of age. The majority (75%) were in private \npractice and 14% practiced in FQHCs. About 54% were part of large practices with over 1500 \npatients. These data are helpful in terms of understanding themes in general. When asked \nwhether they would prefer to provide the Mpox vaccine within their practice, family practitioners \nmore often strongly or somewhat preferred providing the vaccine within their own practice. \nPediatrician s were supportive of the vaccine, but preferred to refer to an outside practice. \nAs Dr. Minhaj showed earlier, there has been a shift over time in vaccine administration from \npublic health clinics to medical care centers. If the ACIP votes in favor of the proposed \nrecommendation, vaccines would be provided in medical centers. However, that already has \nbeen happening. T here has been a statistically significant increase in vaccines provided by \nprimary care offices, FQHCs, and other health centers . This indicates that providers in these \nsettings deem the vaccine to be acceptable. \nA recent CDC online focus group was performed with HCP to further understand their thoughts, \nknowledge, attitudes, and practices related to Mpox . Recruitment done by an external recruiting \nfirm resulted in a group of 41 participants who were diverse in terms of gender, race/ethnicity, \npractice setting, payment methods for patients, and clinical profession. Among the respondents, \n61% reported spending ≥60% of their time providing sexual health services ; 59% were private \nhealthcare settings , 29% were private and publicly funded, and 10% were publicly funded; 54% \nwere in private practice, 20% were STD/HIV/family planning clinic s, 10% were FQHCs , and \n25% were in ED or urgent care settings. Among the respondents, 68% had never managed an \nMpox case , 34%, believe Mpox is a threat to public health, and 32% reported that Mpox is \nimportant to their patient populations. Among respondents, 51% believe that Mpox services \nshould be integrated into standard care. It might improve access to vaccines, education and \nawareness about Mpox for patients, and it would ensure comprehensive STI screening and \ntesting. \nIn response to the question regarding whether the intervention is acceptable to key \nstakeholders, the WG answer was “yes. ” Health departments and clinicians are supportive of \nMpox vaccines, even if pediatricians would prefer to refer patients to other clinics to receive it. \nFamily practitioners would like to be able to actually provide the JYNNEOS vaccine in their own clinics. There has been a shift from JYNNEOS provided by public health providers to JYNNEOS \nprovided by medical center providers, including STI and HIV clinics, where the WG think s these \nvaccines will be administered if this recommendation is passed. \nMoving to the resource use domain, the vaccine is currently provided through the Strategic \nNational Stockpile (SNS) that is intended to stockpile therapeutics for bioterrorism preparedness \nand other similar preparedness issues. JYNNEOS has been stockpiled for smallpox preparedness, but was provided during this response since it is not commercially available. The \ndoses would need to be replenished. There has been and will continue to be a significant use of \nresources (e.g., shipments , transportation, personnel monitoring) during the peak of this \noutbreak. A routine recommendation could be a further drain on the SNS should this vote be \npassed. In the future, it is possible that the vaccine will be commercialized. If so, there are \n44 \n \n    \n   \n \n   \n    \n  \n \n \n \n  \n     \n \n  \n   \n   \n  \n  \n    \n    \n  \n \n \n  \n  \n \n \n \n  \n     \n   \n   \n \n   \n \n  \n \n  \n \n   \n \n   \n  \n  \n \n \n   \n   unknown costs that will be associated with that. Therefore, the WG answered that it is \n“uncertain” whether the intervention is a reasonable and efficient allocation of resources. \nIn terms of the equity domain, the WG interpreted this as trying to understand the population \nwho was impacted by Mpox and felt that there has been a disproportionate impact of Mpox on \ngay, bisexual, and other MSM; B lack and Hispanic persons; and persons experiencing \nhomelessness. Any vaccine administered versus no vaccine administered may decrease the \ndisparity between the affected population and others. The recommendation would facilitate one-\nto-one counseling and information sharing in the privacy of a c linic. Vaccine recommendation \nfrom a clinician is associated with increased vaccine uptake. During September 2023, $5 million \nwere allocated to community -based organizations (CBOs) to advance Mpox prevention and \nvaccination efforts.23 CBOs have played a critical role in the Mpox response so far and are \nessential to increasing vaccination coverage among those at risk. Thus far, 42 CBOs have been \nfunded. If the vaccine is commercialized, there may be an impact on primary sites of vaccination \nin health departments. At this point, it would be conjecture to assume exactly what the impact \nwould be. As previously mentioned, in about 2 to 3 years , it would be necessary to re-assess \nthis interim recommendation knowing the situation at that time in terms of the epidemiology and \nwhether the vaccine is commercialized. However, such a recommendation might facilitate \nproduct acceptance of the vaccination because everybody knows that the ACIP has a high bar \nfor recommending a vaccine. If JYNNEOS vaccine is commercialized in the interim time period, \nthis also would facilitate insurance companies covering the vaccine. \nIn response to the question regarding what the impact would be on health equity, the WG group \nfelt that access to vaccine versus no vaccine may improve the health of persons who are at risk \nfor impacts, and that a routine recommendation may facilitate vaccinations and that health \nequity would be “probably increased. ” \nRegarding the feasibility domain, if the ACIP voted to approve the interim recommendation for \nJYNNEOS vaccine, the vaccine would continue to be provided through the SNS free of cost to \npatients and providers. While there would be a cost overall to the US Government (USG), there \nwould not be a cost to patients and providers. Mpox provider agreements do not have a \ntermination date.24 They will continue as long as the vaccine is acquired via the US G program \nand can include new providers. In fact, CDC learned that health departments are continuing to \nbring on new providers. The $5 million funding that has been provided to CBOs may improve \nfeasibility in addition to equity. The se CBOs reach hard-to-reach communities and also might \nfacilitate feasibility for those communities. If the vaccine is commercialized, it would be available \nthrough Medicare, Medicaid, and commercial plans without a co-pay. Uninsured children would \nbe given the vaccine through the VFC. Some uninsured and underinsured adults could have difficulty , but that would be similar to the difficulty they encounter with other vaccines. \nRegarding whether the intervention is feasible to implement, the WG group answered “probably \nyes.” SQ vaccine is easy to administer, and providers know how to administer it. Standing orders are available. JYNNEOS can be stored refrigerated for 8 weeks. There has been a \nrecent shift in vaccine providers to individual clinics , which demonstrates the continued \nsuccessful integration of JYNNEOS into provider s’ practices (e.g., STI and HIV care settings, \nHIV care pharmacies, LGBTQ+ affirming primary care practices). STI, HIV, and most family \nmedicine/ internal medicine providers seem to be comfortable providing vaccines, even if some \n23 https://www.cdcfoundation.org/pr/2023/mpox-vaccination-CBO-outreach \n24 https://www.cdc.gov/poxvirus/mpox/clinicians/provider-agreement.html \n45 \n \n   \n \n \n     \n \n   \n \n   \n \n  \n     \n \n \n     \n \n \n \n    \n  \n \n \n \n \n  \n     \n \n \n \n \n \n \n \n   \n \n \n  \n   \n    \n \n      \n      \n     \n  \n     pediatricians may refer patients out to other clinics. If commercialized, similar to other vaccines, \nthe cost of vaccine might impact access to some populations. \nTo summarize all of the answers provided in the EtR domains, there is nothing clearly \nunfavorable. However, there is uncertainty pertaining to the variability and values that people \nhave about the vaccine in general. This is possibly because they perceive that there is decreased risk, which is not the case. There is uncertainty about commercialization of the \nvaccine. Based on all of this, the WG determined that the desirable consequences probably \noutweigh the undesirable consequences in most settings. However, several WG members felt \nthat there was enough information presented that the desirable consequences clearly outweigh \nthe undesirable consequences despite the uncertainty . Given that more people in a straw poll \nsupported the “probably outweigh” option, that was what was shown for the balance of \nconsequences. \nIn closing, Dr. Rao posted the proposed recommendation a vote and invited input from the ACIP \nmembers and STD colleagues on the language of this vote. \nDiscussion Points \nDr. Poehling expressed appreciation for the team working with patients and persons who were \ndirectly impacted to co- create the educational materials. While she appreciated the question \nthat was raised about the verbiage in the proposed interim recommendation defining persons at \nrisk, there is overwhelming evidence that the primary sentence as stated in the proposed recommendation would be beneficial. \nDr. Poehling made a motion to approve the language as stated, “ACIP recommends \nvaccination with the 2-dose JYNNEOS vaccine series for persons aged 18 years and older at risk for Mpox.” Ms. Bahta seconded the motion. \nMs. Bahta stressed that it is really important to understand that in terms of the launching of new \nvaccines as well as transitioning from the federal supply to the commercial supply that there will \nbe decreased access. With that in mind, she emphasized the importance of establishing a Vaccines for Adults (VFA) program. Regarding the potential move to a routine recommendation, she asked for input on the current supply. \nDr. Rao indicated that there is plenty of vaccine for all of the people who are eligible for the \nvaccine over the next several years, including people who become eligible during that time period. \nDr. Daley indicated his support for the proposed recommendation and requested a reminder \nabout the duration of protection from vaccination. Dr. Rao said they are hoping to continue to evaluate duration of protection through continuing \nVE work. To her knowledge, the multi -jurisdictional study is the only one out of the 3 studies that \nwill be continuing, though perhaps the New York State study also will be continuing. What is \nknown is that the pre-licensure data indicated that an anamnestic response to the vaccine \noccurs for up to 2 years after the primary 2-dose series. The only reason a booster frequency of \n2 years was proposed for persons at occupational risk for orthopoxviruses was that nobody had \nevaluated a time point later than 2 years. In the Democratic Republic of Congo (DRC), CDC has \na vaccine study that is looking into this. It appears that people have mounted a robust response \n5 years after the initial primary dose series , but they want to evaluate that more before \n46 \n \n    \n \n \n  \n \n   \n  \n  \n   \n     \n \n \n     \n   \n \n \n   \n \n \n   \n   \n  \n   \n \n  \n  \n  \n \n \n  \n \n  \n \n \n \n \n \n \n  \n   \n  \n \n \n \n     \n  \n    \n \n \n confidently express ing this . She called on Drs. McCollum and Panayampalli who led the DRC \nwork to comment further. \nDr. Panayampalli added that participants were classified as those having never received the \nvaccine and those who received the vaccine during childhood. Even after several decades, \npeople who received childhood vaccination demonstrated a robust and anamnestic response. \nThose individuals probably received replicating vaccine previously. JYNNEOS is a non -\nreplicating vaccine, so they also wanted to s ee if JYNNEOS has a similar effect. As Dr. Rao \nmentioned, 5 years after people received JYNNEOS, regardless of whether any circulating \nantibodies were detected, a robust increase is seen in the immune response 7 days after a \nboost. \nDr. Cineas requested information on a timeline for a recommendation for adolescent patients \nwho are at risk . \nDr. Rao reiterated that the reasons the proposed recommendation was for persons 18 years of \nage and older was because the vaccine is currently licensed in that population. There are going to be NIH data from a trial among adolescents 12─17 years of age, hopefully in 2024. She \nnoted that she would explain the clinical guidance data further in her next presentation. \nDr. Beigel (NIH) reported that the adolescent study was fully enrolled in September 2023, which \nmeans the peak immunogenicity visits at 42 days occurred a few days before this meeting. It is \ndesigned to include a 1- year follow -up, which is in October 2024 for the full dataset. NIH can \ndiscuss with the ACIP and Bavarian Nordic about early analyses . \nDr. Zahn (NACCHO) noted that the State of California has simplified the recommendation \nindication that a person who is a practicing MSM who has HIV is recommended to receive the \nvaccine. He has been a fan of that simpler recommendation, given that persons at risk may not \nrecognize they are at risk and/or depending upon the setting, HCP might not be comfortable \ngoing through all of the potential risks. There also is the issue of stigma because someone has \npracticed certain behaviors that are risk factors. While they do not have enormous uptake, he \nwould be disappointed in not continuing to have a broad recommendation since they do continue to have sporadic disease in Southern and Northern California. Outreach to specific community settings has proven to be and will continu e to be valuable. Having the continued \nsupport for their CBO partners and to public health to provide outreach over time is going to be \nimportant. \nDr. Rao agreed with the importance of continuing to support CBOs because they do very \nimportant work, particularly for this population. She noted that a lot of thought was put into whether the recommendation could be simplified, but this is an infection that occurs when there \nare certain behavior risk factors. To recommend the vaccine to anyone who has HIV and/or \nanyone who is MSM perhaps would result in giving the vaccine to people who do not need it but \nmight be concerned about getting Mpox even though they are in a monogamous relationship \nand do not meet the criteria. \nDr. Quilter added that they were trying to strike a balance. She appreciated the comments about \nwanting to avoid stigma and to simplify the recommendation for providers, but also wanting to \nensure that the vaccination being given to those who are most at risk for Mpox exposure. The \nversion proposed was tweaked from an even more complicated version the first time around to \nachieve that balance. \n47 \n \n  \n   \n \n  \n     \n   \n \n \n  \n \n \n \n   \n \n \n \n \n  \n \n     \n  \n \n  \n \n  \n \n \n \n \n  \n \n     \n   \n       \n   \n  \n \n     \n     \n   \n  \n \n \n Dr. Rao asked whether Dr. Spicknall, as a modeling expert in the Division of STD prevention, \nhad any thoughts about just how much bigger the population would be if it was referring to all \nMSM or all people with HIV versus how it is described in the proposed recommendation. \nDr. Spicknall said that in terms of a larger population, it would go from roughly 2 million to 4 to 6 \nmillion people. The scope would be enlarged greatly such that folks who may not benefit from \nthis vaccine for the reasons described would be vaccinated. \nDr. Drees (SHEA) observed that the list of people who are at risk in the proposed recommendation did not mention occupational exposures, and she wondered whether that was intentional because it would be a separate vote or if it needed to be included in this recommendation. \nDr. Rao indicated that occupational exposures intentionally were not included in this proposed \nrecommendation because this is intended to be PrEP for the population at risk of acquiring Mpox in the current outbreak. There already are standing occupational recommendations for laboratorians and HCP on which the ACIP voted in February 2022 in terms of who needs to be vaccinated during an outbreak. Because so few healthcare- association infections have been \nacquired, it is not routinely recommended for clinicians who are providing care to patients who have or might have Mpox. Being in the midst of an outbreak, many laboratorians have been and \ncan continue to be vaccinated. \nDr. Drees (SHEA) said that “wearing her other hat” as a practicing HIV provider that her state also allows anyone with HIV to be vaccinated. Clinicians have to talk about many vaccines with \ntheir populations, so she does not routinely offer Mpox vaccine to every person living with HIV \nbecause she knows many of them are not at risk. \nDr. Middleman asked about the rationale for inclusion of non -binary and transgender people. \nTransgender males are assigned female at birth, so it was not clear to her what the risk factors \nwere if not just receptive anal intercourse and if there was something different about \ntransgender males and non-binary people that put them at higher risk. She emphasized that she wanted to make sure that they were not making assumptions of behavior or increased risk based on gender identity status. \nDr. Quilter indicated that the population of persons at increased risk in the proposed \nrecommendation was based on gender identity and sexual orientation. She did not know if there \nwas enough information yet to specify a behavior. Based on how Mpox is transmitted through \nintimate or sexual contact, it could be any skin-to -skin contact with mucosal infections. It is \npossible through oral sex, insertive or receptive anal sex, or other mucosal exposure. The \ndecision about persons at risk was data-driven. A CDC MMWR was published earlier in the year \nthat was dedicated specifically to the epidemiology of Mpox in persons who are transgender or \nnon-binary people. The authors found that these populations  were disproportionately affected by \nthe Mpox outbreak. Cisgender women have been minimally impacted. There has been a \ndisproportionate impact on Mpox transgender and non-binary people. The exact wording used \nin the MMWR was reviewed and endorsed by CDC’s health equity experts so that the \nrecommendation could be as inclusive as possible and ensure that the people who are known to \nbe at risk are getting vaccinated. \nDr. Rao added that they know of cases of people lying very close together without clothing on and having contact with the lesions in the genital region. There have been people who said they \n48 \n \n  \n  \n \n  \n \n \n \n  \n \n   \n  \n   \n  \n  \n     \n \n    \n \n \n      \n   \n      \n    \n  \n   \n   \n    \n    \n   \n   \n    \n    \n   \n   \n     \n \n \n   \n     \n \n \n  \n \n     \n \n   \n  \n  \n  had penetrative sex, receptive sex, heterosexual women who seem to have acquired it from \nbisexual men. \nDr. Spicknall pointed out that the modeling evidence suggests that not only are personal \nindividual -level risk factors and behavioral adaptations occurring, but also it is a group of people \nacting together that in effect decreases transmission. \nDr. Lee recapped that in the adolescent population, Dr. Middleman was highlighting the \nassumption issue. As they begin to think about the adolescent age group, they will have to \nquestion the recommendations to ensure that they are not reinforcing potential stereotypes. \nDr. Boucher (ASPR/ HHS ) reported that since the identification of Mpox cases in the US in May \n2022, Administration for Strategic Preparedness and Response (ASPR) has shipped over 1 \nmillion vials of JYNNEOS to federal and jurisdictional partners. As Dr. Rao and others \nmentioned, JYNNEOS was developed by Bavarian Nordic and USG partners like the Biomedical Advanced Research and Development Authority (BARDA), and others as part of the \nnation’ s smallpox preparedness program. Given its safety profile, particularly for \nimmunocompromised individuals , and effectiveness in reducing the frequency and severity of \ninfections, there was a strong justification to use doses held in the SNS to support the response. \nIn continuing to move beyond the acute phase of the response, ASPR is supportive of the \ntransition of JYNNEOS to commercial distribution as the next correct step in ensuring continued \naccess for those who wish to get vaccinated for Mpox. ASPR also is committed to ensuring a \nseamless transition if this does go to commercial distribution. There will not be gaps in the \navailability of JYNNEOS as ASPR “passes the baton” onto its partners at Bavarian Nordic. In \nJanuary 2023, ASPR migrated jurisdictional ordering to a threshold-based system that is similar \nto that used for COVID v accines and therapeutics. At that time, about 400,000 vials were put \ninto the combined thresholds across 64 jurisdictions. To date, about 57,000 of those have been \nordered. That means that there are still well over 300,000 vials available immediately to \njurisdictions anytime they need to restock existing vaccination sites or supply new ones. ASPR \nwill keep this supply reserve for the jurisdictions as they work with Bavarian Nordic and HHS \npartners at CDC, CMS , and several others over the coming months in order to plan and execute \na smooth handoff. Regarding the question earlier about the largest supply , through ASPR’s \npartnership with Bavarian Nordic and a lot of great efforts that they have made to expand \nmanufacturing capacity and deliveries over the last year and a half, ASPR significantly built its \nJYNNEOS inventory in that period. If the JYNNEOS vaccine transitions to commercial \ndistribution and there is a point at which demand is outpacing BN’s manufacturing capacity, \nASPR would still consider itself to partner with Bavarian Nordic and would be happy to work \nthrough ways that they might be able to provide support to avoid any shortages. He recognized \nthat there were many people participating in the meeting who play viral roles in providing care to \npatients and reducing Mpox cases. On behalf of all of his colleagues at ASPR, he expressed \ngratitude for everything they do to keep people safe and healthy and thanked them for their \npartnership throughout the response. \nLee Ann Kimak (Bavarian Nordic) indicated that she is the US Commercial Lead at Bavarian \nNordic . On behalf of Bavarian Nordic, she thanked the WG and the ACIP for their tremendous \nefforts and their careful deliberations on this important public health issue. Bavarian Nordic is \nvery proud to have partnered with the US G in the successful response to meet the Mpox \noutbreak, including the rapid deployment of JYNNEOS. They also realize that vaccine access \nchallenges remain. They believe that the routine preventative recommendation for at-risk \npopulations under consideration by the ACIP is a critical step forward in addressing these \ninequities and access challenges. This recommendation would allow providers and retail \n49 \n \n   \n \n  \n     \n  \n  \n   \n \n \n   \n  \n \n  \n  \n  \n \n \n  \n \n  \n \n  \n    \n   \n  \n   \n \n    \n    \n   \n    \n     \n    \n \n     \n  \n \n     \n   \n \n   \n  \n  \n    \n  \n   \n   \n    \n  \n  \n     pharmacies to administer the vaccine where people are most comfortable seeking one, whether \nthat is at the pharmacy, their doctor's office, or their neighborhood health clinic. If the committee \nvotes for a routine recommendation for the at-risk population, putting Mpox vaccine on the \nimmunization schedule, Bavarian Nordic very much looks forward to commercializing JYNNEOS \nin the US. They have a robust manufacturing process and ample supply to meet the need. They \nalso have an unwavering commitment to public health and look forward to working with the \nagency and healthcare providers in the community to make this vaccine accessible to \nindividuals at risk. \nDr. Sanchez asked whether Ms. Kimak could comment on the anticipated price of the \nJYNNEOS vaccine . \nLee Ann Kimak (Bavarian Nordic) reported that the intended list price will be in the range of \n$200 to $270 per dose. The list price is then negotiated down in the contracting phase, \ndepending upon the particular reimbursement mechanism. It comes down by 25% to 30% or \nmore , which is the range for the wholesale acquisition cost. \nReview of Voting L anguage and Clinical G uidance \nAgam Rao, MD (CDC/NCEZID; CAPT, US Public Health Service) indicated that this \npresentation was dedicated to guidance about whether the proposed interim recommendation \nshould be passed and next steps. This guidance refers to vaccination before exposures to \nMpox , not post-exposure prophylaxis (PEP). Much of the guidance is similar or identical to what \nshe presented during the June 2023 ACIP meeting. All of this guidance refer s to the individuals \nlisted in the footnote included with the proposed interim recommendation who would be eligible \nfor the vaccine and for PrEP only. \nJYNNEOS is not licensed for persons <18 years of age. There are no pre pre-licensure studies \nin this population. However, vaccine has been administered to this population. While a good \nnumber of adolescents 12─17 years of age received a first dose of the JYNNEOS vaccine, CDC \nhas not received any concerning safety signals in this population or VAERS reports of SAEs in \nthis age group. For the NIH clinical trial in progress focused on s afety and immunogenicity of \nJYNNEOS in persons aged 12─ 17 years of age, it sounds like data may be available by the end \nof 2024 and perhaps the earliest it could be presented to ACIP would be in  2025. That is why \nguidance is proposed saying that adolescents at risk for Mpox may receive the JYNNEOS \nvaccine before an exposure, which refer to adolescents with risk factors. \nIn terms of pregnancy or breastfeeding, available human data are insufficient to determine \nwhether the vaccine has any risks in pregnant persons. However, animal model data are \nmentioned in the package insert. This includes models involving rats that have shown no \nevidence of harm to the developing fetus. No AEs have been reported to the US vaccine safety \nsurveillance systems . They do not have data showing how many pregnant persons have \nreceived the vaccine during this response. However, it is reassuring that at least there have not \nbeen VAERS reports of anyone actually indicating that an AE was in a pregnant person. \nSimilarly for breastfeeding persons, this has not been evaluated and there have been no AE \nreports reported in the US vaccine safety surveillance systems. JYNNEOS is not \ncontraindicated in pregnancy or while breastfeeding, and CDC has stated such in the \noccupational recommendations that were published about the use of JYNNEOS in 2022. After \ndiscussing this with the American College of Obstetricians and Gynecologists (ACOG) WG \nmember and others, the decision was made for the clinical guidance to be, “Pregnant or \nbreastfeeding persons at risk for Mpox may receive the JYNNEOS vaccine before an exposure.” \n50 \n \n  \n \n \n \n  \n  \n    \n \n \n  \n   \n \n  \n \n   \n   \n   \n  \n  \n     \n   \n   \n  \n  \n \n     \n  \n   \n   \n   \n    \n \n  \n \n  \n    \n   \n \n \n \n   \n \n   \n   \n   \n \n   \n   Again, this is referring to those people with the risk factors, not all pregnant or breastfeeding \npersons. \nMoving to HCP, healthcare-associated Mpox infections have been rare and typically associated \nwith sharps injuries or exposure in the absence of personal protective equipment (PPE). There \nhave been very few cases, as discussed during the June 2023 ACIP meeting, especially among people using the PPE that they should be using. HCP at risk for Mpox because of the risk factors described (e.g., MSM with more than one sexual partner) should be vaccinated. \nHowever, this recommendation is not because of occupational risk. The guidance is that \nJYNNEOS is not recommended as a routine vaccination for healthcare personnel unless sexual \nrisk factors are present.” \nThere is a known risk for m yopericarditis after ACAM2000, which is the other orthopoxvirus \nvaccine used in the US. Given that the mechanism is unknown, a theoretical risk with \nJYNNEOS has not been ruled out yet. There is a known risk after COVID- 19 vaccines, \nparticularly in adolescent and young adult males. That is the reason that the CDC websites for \nCOVID -19 and Mpox vaccines provide interim guidance for co-administration of JYNNEOS with \nCOVID -19 vaccines . CDC’s interim guidance in the clinical considerations for coadministration \nof JYNNEOS vaccine with COVID -19 vaccines\n25 states that, “There is no required minimum \ninterval between receiving any COVID -19 vaccine and JYNNEOS vaccine (e.g., for Mpox \nprevention), regardless of which vaccine is administered first. People, particularly adolescent \nand young adult males, who are recommended to receive both vaccines might consider waiting \n4 weeks between vaccines. This is because of the observed risk for myocarditis and pericarditis \nafter receipt of ACAM2000 orthopoxvirus vaccine and COVID -19 vaccines and the hypothetical \nrisk for myocarditis and pericarditis after the JYNNEOS vaccine. However, if a patient's risk for Mpox or severe disease due to COVID -19 is increased, administration of JYNNEOS and \nCOVID -19 vaccines should not be delayed.” \nThe WG talked about the JYNNEOS vaccine and immunoglobulin products in detail, and it was \npresented to ACIP during the June 2023 meeting. The reason this came up is because technically , the JYNNEOS vaccine is a live virus vaccine. However, it is a non-replicating virus \nvaccine. The WG determined that there are no precautions necessary if JYNNEOS is \nadministered in close temporal proximity to intravenous immunoglobulin (IVIG ). With regards to \nvaccinia immunoglobulin intravenous (VIGIV ), which is a product that basically is pooled from \npersons who are vaccinated with ACAM2000, it perhaps could interfere with the immune \nresponse to the JYNNEOS vaccine. Ideally, administration of JYNNEOS should be delayed if \nVIGIV was recently administered. The reason that VIGIV is probably administered to a patient is \na severe manifestation of Mpox . At this time, those are persons for whom vaccination would not \nbe recommended since they have acquired Mpox. Currently, the recommendation is that people \nwho have recovered from Mpox do not need to be vaccinated. Therefore, this is not likely to \ncome up very often if at all. If it does come up, a public health consultation should be obtained \nfor case-specific guidance. \nAs far as contraindications and precautions , JYNNEOS was licensed for prevention of smallpox \nin addition to prevention of Mpox .\n26 Because smallpox is nearly always life -threatening, there \nare no absolute contraindications for the use of JYNNEOS to prevent smallpox. That is why the \npackage insert does not list an absolute contraindication. However, the considerations may be \ndifferent for Mpox. Consistent with contraindications and ACIP routine schedules, the WG \n25 https://www.cdc.gov/vaccines/covid-19/clinical-considerations/interim-considerations-us.html \n26 https://www.fda.gov/media/131078/download \n51 \n \n  \n    \n  \n  \n \n  \n   \n       \n    \n  \n   \n  \n  \n  \n \n   \n  \n   \n    \n   \n  \n \n \n \n \n  \n \n \n \n \n  \n \n \n \n \n   \n  \n \n  \n   \n  \n  \n    \n  \n   \n  \n    \n proposed stating that JYNNEOS is contraindicated in patients with severe allergic reaction, \n(e.g., anaphylaxis) after a previous dose of the vaccine or to a vaccine component. Under \nprecautions, the WG proposed making a statement similar to what is listed for pretty much all \nvaccines, “Precautions: Moderate or severe acute illness, with or without fever .” \nFor other administration guidance, the WG wanted to stress that completion of the 2- dose series \nshould be encouraged. If there is one message that hopefully comes from this meeting, it is that \nMpox cases are still occurring, and this is not over. If people got only 1 dose or did not seek the \nvaccine because there was not as much availability as last year, the hope is that they will reach \nout now and get vaccinated as much as possible. Getting the second dose into arms would be \nreally great for those individual patients , their friends , and others. The second dose should be \nadministered at about 28 days after the first dose. However, the second dose can still be \nadministered even if over a year has elapsed. Restarting the series is not required and the \nsecond dose should be administered as soon as possible. \nIn terms of next steps, Dr. Rao explained that the Mpox WG is not going away completely . They \nwill publish the 2 MMWR ACIP recommendations about the use of JYNNEOS during outbreaks \nand the use of JYNNEOS among persons at risk during the ongoing Mpox outbreak in 2024 \nbecause they are compl ementary. Once the data are available from the NIH, perhaps the WG \nwill reconvene toward the end of 2024 and potentially will present the data to the ACIP in early \n2025. If passed, the recommendation will be revisited in 2 to 3 years when more data are \navailable about the epidemiology to help decide whether this recommendation should be \ncontinued. The WG will revisit the E tR review, epidemiology , cost-effectiveness analys es, and \nother data and will present that to the ACIP to determine whether this should be continued. In \nthe interim, this recommendation would exist if it is passed. If the vaccine becomes \ncommercialized, there would be additional tasks that would need to be addressed. \nDiscussion Points \nDr. Poehling expressed appreciation for the tentative timeline and the thought of continuing to \nevaluate the impact to make sure the recommendations are precise and are having the desired \nimpact. She stated that one question that we focus on for safety is myopericarditis. In the doses \nof JYNNEOS administered in the United States, we have not seen cases of myopericarditis in VAERS or VSD, but that does not exclude it occurring rarely, is that correct? \nDr. Duffy expressed that is the correct understanding on safety for JYNNEOS. \nDr. Loehr asked if Ms. Kimak could comment on how long the manufacturer thinks it would take \nto commercialize this vaccine. \nLee Ann Kimak (Bavarian Nordic) indicated that Bavarian Nordic began taking steps toward \ncommercializing the product as soon as they learned that the ACIP would be considering a \nrecommendation. If JYNNEOS is routinely recommended for those at risk of Mpox , this would \nallow Bavarian Nordic to move forward with some of the steps toward commercial insurance \ncoverage. They anticipate that it will take a number of months to negotiate these contracts and \nbe prepared to work through all of the necessary steps with a variety of payers in terms of \nsetting up the distribution channels to store and administer the vaccine. As with the commercial \ntransition of the COVID vaccines, this process can take some time. However, she would not \nforesee it being outside of the 6- to 9-month range. \n52 \n \n   \n \n \n \n  \n  \n \n   \n \n \n  \n \n \n \n \n  \n \n \n  \n   \n \n \n \n \n  \n   \n  \n \n  \n \n \n \n   \n \n \n \n \n \n    \n \n        \n        \n \n   \n  \n \n \n \n \n Dr. Loehr emphasized the need for a cost-benefit analysis. The ACIP basically would be voting \non and approving the interim recommendation which could be extremely costly, yet they have \nno sense of that. He noted that while he was in favor of the recommendation based on the \ncurrent status, he wanted it to be reviewed as soon as the new data become available. \nDr. Lee pointed out that all of the ACIP’s recommendations are interim and could be revisited at \nany moment. She suggested dropping the terminology “interim recommendation” similar to what \nthey did for pneumococcal vaccines. The ACIP does not have “strong recommendations ” or “not \nstrong recommendations.” She agreed with Dr. Loehr’s point about the cost-effectiveness analysis . The unusual nature by which this vaccine is coming to market makes it somewhat \ncomplicated. \nAs a reminder, public comment was presented prior to the votes. However, the votes were \ncombined in this proceedings document with their respective sessions for the purpose of \ncontinuity. \nVote: Mpox Vaccine Recommendation \nAgam Rao, MD (CDC/NCEZID; CAPT, US Public Health Service) presented the proposed \nrecommendation for a vote as follows: \nACIP recommends vaccination* with the 2-dose† JYNNEOS vaccine series for persons \naged 18 years and older at risk for Mpox§ \n*Interim recommendation that ACIP will revisit in 2-3 years \n†Dose 2 administered 28 days after dose 1 \n§Persons at risk: \n• Gay, bisexual, and other men who have sex with men, transgender or nonbinary people who in the past 6 months have had one of the following: \n− A new diagnosis of ≥ 1 sexually transmitted disease \n− More than one sex partner \n− Sex at a commercial sex venue \n− Sex in association with a large public event in a geographic area where Mpox transmission is occurring \n• Sexual partners of persons with the risks described in above \n• Persons who anticipate experiencing any of the above \nMotion/Vote: Mpox Vaccine Recommendation \nDr. Poehling moved to accept the Mpox vaccine recommendation language as presented, which \nMs. Bahta seconded. No COIs were declared. The motion carried with 14 affirmative votes, 0 negative votes, and 0 abstentions. The disposition of the vote was as follows: \n14 Favored: Bahta, Bell, Brooks, Chen, Cineas, Daley, Kotton, Lee, Loehr, Long, McNally, Poehling, Sanchez, Talbot \n0 Opposed: N/A \n0 Abstained: N/A \n53 \n \n  \n  \n \n   \n \n     \n \n    \n  \n \n  \n   \n  \n   \n \n   \n   \n \n  \n  \n  \n  \n  \n \n \n \n \n  \n \n     \n \n \n \n \n    \n \n \n \n \n     \n \n \n \n \n   \n \n \n Vote: VFC Mpox R esolution \nDr. Jeanne Santoli (CDC/NCIRD) presented the VFC Mpox Resolution for the ACIP’s \nconsideration and vote. The purpose of this resolution is to add a vaccine for the prevention of \nMpox to the V FC program. The eligible groups are as follows: \nChildren aged 18 years of age at increased risk of Mpox, including: \nPersons who are gay, bisexual, and other men who have sex with men, transgender \nor non-binary people who in the past 6 months have had: \n− At least 1 sexually transmitted disease \n− More than 1 sex partner \n− Sex at a commercial venue \n− Sex in association with a large public event in a geographic area where Mpox \ntransmission is occurring \nPersons who are sexual contacts of the persons described above \nPersons who anticipate experiencing any of the situations described above \nThe recommended schedule and dosage intervals are 2 doses given 28 days apart . The \nrecommended dosages refers the reader to the product package inserts. Similarly for \ncontraindications, there is a referral to the package insert and precautions include moderate or \nsevere acute illness with or without fever. There will be the statement referencing future \npublished recommendations that will be incorporated by reference. \nGiven the discussions, the following bullets convey vaccine availability through the VFC: \nMpox vaccines will not be available through the VFC program immediately following the \npassage of this resolution because they are not yet commercially available. \nAt this time, Mpox vaccines remain available under the HHS Mpox Vaccination Program . \nFollowing the passage of this resolution, CDC will begin the steps necessary to solicit \nfor/award contracts for Mpox vaccines. \nThe timeline for availability of Mpox vaccines commercially or through the VFC program has \nnot yet been finalized. \nDiscussion Points \nDr. Talbott pointed out that this vaccine is the perfect example of why a Vaccines for Adults \nprogram is needed. \nDr. Talbot made a motion to accept this language as proposed. Dr. Poehling seconded \nthe motion. \n54 \n \n  \n \n \n  \n \n   \n \n \n     \n \n        \n        \n \n \n \n \n \n \n \n   \n \n \n  \n \n  \n \n  \n \n \n  \n   \n   \n    \n    \n  \n  \n    \n    \n \n \n \n  \n  \n   \n \n \n    \nMotion/Vote: VFC Mpox Resolution \nDr. Talbot moved to accept the VFC Resolution for the Mpox vaccine recommendation as \npresented, which Dr. Poehling seconded. No COIs were declared. The motion carried with 14 \naffirmative votes, 0 negative votes, and 0 abstentions. The disposition of the vote was as \nfollows: \n14 Favored: Bahta, Bell, Brooks, Chen, Cineas, Daley, Kotton, Lee, Loehr, Long, McNally, \nPoehling, Sanchez, Talbot \n0 Opposed: N/A \n0 Abstained: N/A \nADULT RESPIRATORY SYNCYTIAL VIRUS (RSV) VACCINES \nIntroduction \nCamille Kotton, MD (Chair, Adult RSV WG) introduced the Adult RSV WG. She reminded \neveryone that in June 2023, the ACIP voted to recommend that adults ≥60 years of age may \nreceive a single dose of RSV vaccine using shared clinical decision-making.27 There are 2 FDA-\napproved RSV vaccines , which are as follows: \nRSVPreF3 (Arexvy, GSK) is a 1 -dose adjuvanted (AS01E) recombinant prefusion F protein \n(preF) vaccine. \nRSVpreF (Abrysvo , Pfizer) is a 1-dose recombinant preF vaccine. \nIssues under discussion since the June ACIP meeting include that the WG reviewed CDC \nsafety surveillance plans for RSV vaccination in adults ≥60 years of age. GSK has shared with \nthe WG results of an immune-bridging study showing non-inferior hum oral immune responses to \nRSV vaccination in immunocompetent adults 50 ─59 years of age compared with \nimmunocompetent adults ≥60 years of age in whom efficacy was demonstrated. To be clear, \nthis is just a serology study, not an efficacy study. The WG discussed the potential role of RSV \nvaccination in adults younger than 60 years of age, including subpopulations who would benefit \nmost from vaccination and equity implications . The WG reviewed CDC vaccine surveillance \nsafety plans for RSV vaccination in adults ≥60 years of age, including V -safe that has launched \nfor older adult RSV vaccination. Dr. Kotton encouraged everyone listening to this meeting who \ninteracts with people who are getting the adult RSV vaccine to encourage them to sign up for V -\nsafe so that there will be as much clinical information about this vaccine as possible. \nThis s ession did not include RSV vaccine uptake data or safety surveillance data as those data \nwere premature early into the vaccination program. U ptake and safety results will be shared \nduring a future ACIP meeting. This session included the following topics: \n27 https://www.cdc.gov/mmwr/volumes/72/wr/mm7229a4.htm \n55 \n \n    \n \n  \n   \n \n \n  \n  \n     \n  \n  \n  \n \n \n \n   \n   \n      \n  \n \n \n  \n    \n  \n  \n \n     \n    \n \n \n   \n \n     \n   \n  \n   \n \n     \n   \n    \n      \n \n      \n    \n    \n  \n \n \n \n  RSVPreF3 safety and immunogenicity in adults 50– 59 years of age, compared with adults \n≥60 year s of age \nEpidemiology of RSV hospitalization in adults, with a focus on adults 50– 59 years of age \nWG considerations regarding RSV vaccination in adults 50– 59 years of age \nGSK Safety and Immunogenicity in Persons 50-59 Years of Age \nSusan Gerber, MD (Medical Director, Adult RSV vaccines, GSK) presented an RSVPreF3 + \nAS01 E (AREXVY) safety and immunogenicity update in adults 50─ 59 years of age. Beginning \nwith a brief background of RSV disease i n this population, there is substantial RSV burden and \nunmet medical need in adults 50─ 59 years of age. Rates of RSV -associated hospitalizations \nand medically -attended RSV illnesses are relatively high in this age group related to the \ndevelopment of immuno senescence and increased incidents of certain comorbidities. Published \nincidence rates likely substantially underestimate RSV burden due to lack of awareness, \nstandardized testing, and under -detection within surveillance studies. Chronic underlying \nmedical conditions or co -morbidities that are associated with severe RSV disease such as \nchronic obstructive pulmonary disease (COPD ), congestive heart failure, diabetes, asthma, \nchronic liver disease (CLD), and chronic kidney disease (CKD) are prevalent in this age group. \nAdditionally, observed disparities by race and ethnicity are particularly pronounced with respect to hospitalization rates among middle-aged adults 50─ 64 years of age. \nData from the CDC surveillance platform, RSV-NET, on unadjusted RSV-associated \nhospitalization rates by race and ethnicity for the last 5 seasons for persons 50─ 64 years of age \nidentified consistent disparities among Hispanic, American Indian/ Alaska Native (AI/AN), and \nBlack Americans as compared with White non- Hispanic Americans.\n28 Along these lines, a \nrecent presentation at IDW eek 2023 from Dr. Angela Branch e and colleagues showed that \nyoung and middle-aged adults with certain underlying co-morbid conditions are at high risk for \nRSV-associated hospitalization, with potentially a disproportionate risk for Black and Hispanic \nmiddle-aged adults. \nBased on this unmet medical need, GSK conducted a study to evaluate their RSV vaccine in \nimmunocompetent adults 50─ 59 years of age.29 The primary objective was to demonstrate the \nnon-inferiority of the hum oral immune response after RSVPreF3 + AS01 E vaccine administration \nin adults 50 ─59-years of age with and without co-morbidities well -documented to be related to \nRSV-associated severe disease compared to older adults ≥60 years of age. GSK previously \nestablished high vaccine efficacy against symptomatic RSV illness in adults ≥ 60 years of age. \nPrimary endpoints were to evaluate the non-inferiority of RSV-A and RSV -B neutralization titers \nat 1 month following vaccine administration for 2 adult groups 50─59 years of age, with and \nwithout co- morbidities associated with RSV lower respiratory tract disease (RSV -LRTD ), as \ncompared to adults ≥60 years of age. Success criteria is defined as the upper limit of the 2-\nsided 95% confidence interval for the geometric mean titer (GMT) ratio of ≤ 1.5 and the \nseroresponse rate difference of ≤ 10%. Additional immunogenicity endpoints will be examined at \n6 and 12 months as the study continues . Frequency of CD4+ T cells were assessed in subsets \nof adults 50 ─59 years of age and ≥60 years of age to evaluate the cell -mediated immune \nresponse. Safety endpoints also were included. \n28 Graphs independently created for GSK from original data; A/PI, Asian and Pacific Islander, AI/AN, America Indian or Alaska \nNative; CDC, https://www.cdc.gov/rsv/research/rsv-net/dashboard.html  (accessed October 2023) \n29 ClinicalTrials.gov. NCT05590403. https://www.clinicaltrials.gov/study/NCT05590403; (accessed September 2023) \n56 \n \n      \n       \n    \n   \n   \n  \n  \n    \n   \n  \n \n \n  \n \n \n \n \n    \n   \n \n    \n   \n     \n   \n    \n  \n   \n      \n     \n \n \n   \n    \n  \n   \n     \n      \n  \n  \n   \n \n   \n   \n   \n   \n    \n   \n  \n \n  \n \n The study is a randomized, placebo- controlled, observer-blind, multi -country study. Cohorts 1a \nand 1b were randomized 2:1 to receive vaccine or placebo. Cohort 1a are adults 50─59 years \nof age with co-morbidities associated with RSV- LRTD and Cohort 1b are adults 50─59 years of \nage without co-morbidities associated with RSV -LRTD. Cohort 2a are adults ≥60 years of age. \nThis standard immune -bridging, non- inferiority approach has been developed to bring vaccines \nfaster to those at high risk for severe disease, such as COVID -19 vaccines, and was developed \nand agreed upon in consultation with the FDA. This presentation focused on the preliminary 1-\nmonth immunogenicity and 6-month safety results. This study included participants from 8 \ncountries; approximately 23% were from the US. Demographic and clinical characteristics were \nwell-balanced between the vaccine and placebo groups. O f the adults ≥60 years of ag\n…[truncated]", "summary": "MEETING OF THE ADVISORY  COMMITTEE ON IMMUNIZATION  PRACTICES (ACIP)  OCTOBER 25 -26, 2023  MEETING SUMMARY  CONTENTS   WEDNESDAY: OCTOBER 25, 2023 .............................................................................. 4  Safety of Quadrivalent Recombinant Influenza Vaccine in Pregnant Women and Their  Safety of Simultaneous versus Sequential Administration of mRNA COVID -19 and   Quadrivalent Inactivated Influenza (IIV4) Vaccines: A Randomized Placebo Controlled Trial Safety of…", "source_url": "https://www.cdc.gov/acip/meetings/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/minutes/summary-2023-10-25-26-508.pdf", "doc_date": "2023-10-25", "case": "acip", "sub_case": "minutes", "tags": ["acip", "cdc", "vaccines", "minutes"], "page_count": 177}
{"title": "agenda 2023 09 22 508", "content": "FINAL - September  19, 2023 \nMEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP) \nCenters for Disease Control and Prevention \nAtlanta, Georgia 30329  \nSeptember 22, 2023 \nAGENDA ITEM \n10:00 Welcome and introductions \n10:30 Introduction \n10:40 RSVpreF Vaccine Safety Surveillance in Pregnancy from The \nVaccine Safety Datalink \nMaternal RSV vaccine safety monitoring in the VAERS and V-\nsafe \n11:10 Economic analysis of RSVpreF maternal vaccination \n11:30 Economics of Preventing RSV Disease among US Infants by  \nMaternal Vaccination Prior to Birth \n12:00 \nEtR Framework Updates: Pfizer Maternal RSVpreF Vaccine \n12:30 Updated clinical considerations for use of both nirsevimab  \nand Pfizer RSVpreF vaccine \n12:40 Implementation considerations for maternal RSV vaccine \n2:05 Vaccines for Children Resolution \n2:20 Break \n2:30 Public comment \n2:50 Break \n2:55 Recommendation and VFC votes \n3:20 Adult and Pediatric Immunization Schedule Addendum PRESIDER/PRESENTER(s) \nDr. G race Lee (ACIP C hair) \nDr. Mel inda Wharton ( ACIP E xecutive \nSecretary, C DC) \nDr. S arah L ong (A CIP, W G Chair) \nDr. M alini DeSilva ( HealthPartners I nstitute) \nDr. P edro M oro (C DC/NCEZID) \nDr. D avid H utton (University o f Michigan) \nDr. I smael O rtega-Sanchez (CDC/NCIRD) \nDr. K atherine F leming-Dutra ( CDC/NCIRD) \nDr. J efferson J ones (CDC/NCIRD) \nDr. G eorgina Peacock ( CDC/NCIRD) \nDr. Jeanne Santoli (CDC/NCIRD) \nDr. Sarah Schillie (CDC/NCIRD) \n4:00 Adjourn \nAcronyms \nCDC Centers for Disease Control and Prevention \nCMS Centers for Medicare and Medicaid Services  \nCOVID-19 Coronavirus disease 2019 \nEtR Evidence to Recommendations Framework \nFDA Food and Drug Administration \nGRADE Grading of Recommendations Assessment, Development and Evaluation \nHRSA Health Resources and Services Administration \nIHS Indian Health Service \nNCHHSTP National Center for HIV, Hepatitis, STD and TB Prevention [of CDC/DDID]  \nNCIRD National Center for Immunization & Respiratory Diseases [of CDC/DDID]  \nNCEZID National Center for Emerging and Zoonotic Diseases [of CDC/DDID] \nNIAID National Institute of Allergy and Infectious Diseases \nOIDP Office of Infectious Disease and HIV/AIDS Policy \nRSV Respiratory Syncytial Virus \nSARS-CoV-2 Severe Acute Respiratory Syndrome Coronavirus 2 \nVAERS Vaccine Adverse Event Reporting System \nWG Work Group \nWHO World Health Organization \nVaST COVID-19 Vaccine Safety Technical (VaST) Work Group \nVE Vaccine Effectiveness", "summary": "FINAL - September  19, 2023  MEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)  Centers for Disease Control and Prevention  Atlanta, Georgia 30329   September 22, 2023  AGENDA ITEM  10:00 Welcome and introductions  10:30 Introduction  10:40 RSVpreF Vaccine Safety Surveillance in Pregnancy from The  Vaccine Safety Datalink  Maternal RSV vaccine safety monitoring in the VAERS and V- safe  11:10 Economic analysis of RSVpreF maternal vaccination  11:30 Economics of Preventing RSV…", "source_url": "https://www.cdc.gov/acip/meetings/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/agendas/agenda-2023-09-22-508.pdf", "doc_date": "2023-09-22", "case": "acip", "sub_case": "agendas", "tags": ["acip", "cdc", "vaccines", "agendas"], "page_count": 1}
{"title": "summary 2023 09 22 508", "content": "MEETING OF THE ADVISORY \nCOMMITTEE ON IMMUNIZATION \nPRACTICES (ACIP) \nSEPTEMBER 22 , 2023 \nMEETING SUMMARY \nCONTENTS  \nFRIDAY: SEPTEMBER 22, 2023 .................................................................................................................. 2 \nWELCOME AND INTRODUCTIONS ........................................................................................................ 2 \nCall to Order/Roll Call ........................................................................................................................... 2 \nAnnouncements .................................................................................................................................... 2 \nMATERNAL/PEDIATRIC RESPIRATORY SYNCYTIAL VIRUS (RSV) VACCINES ................................ 3 \nSession Introduction .............................................................................................................................. 3 \nRSVpreF Vaccine Safety Surveillance in Pregnancy from the VSD ..................................................... 4 \nMaternal RSV Vaccine Safety Monitoring in VAERS and v -safesm....................................................... 8 \nAn Economic Analysis of RSVpreF Mater nal Vaccination .................................................................. 10 \nEconomics of Preventing RSV Disease among US Infants by Maternal Vaccination Prior to Birth ...13 \nEtR Framework Updates : Pfizer Maternal RSVpreF Vaccine.............................................................17 \nUpdat\ned Clinical Considerations for Use of Both Nirsevimab and Pfizer RSVpreF Vaccine .............. 28 \nImplementation Considerations for Maternal RSV Vaccine ................................................................ 32 \nVaccines for Childrens Resolution ...................................................................................................... 34 \nPfizer Statement .................................................................................................................................. 36 \nLiaison Organization Statements ........................................................................................................ 37 \nACIP Discussion Points, Observations, Suggestions for RSV Vaccine .............................................. 38 \nPUBLIC COMMENTS .............................................................................................................................. 47 \nOverview ............................................................................................................................................. 47 \nPublic Comments ................................................................................................................................ 47 \nVOTES ..................................................................................................................................................... 49 \nVote #1 RSV Maternal RSV Vaccine Recommendation ..................................................................... 49 \nVote #2 VFC Resolution Maternal RSV Vaccine ................................................................................ 49 \nADULT AND PEDIATRIC IMMUNIZATION SCHEDULE ADDENDUM .................................................. 52 \nPresentation ........................................................................................................................................ 52 \nLiaison Statements .............................................................................................................................. 54 \nCERTIFICATION ......................................................................................................................................... 58 \nACIP MEMBERSHIP ROSTER .................................................................................................................. 59 \nACRONYMS USED IN THIS DOCUMENT ................................................................................................. 68 \n \n  \n  \n \n  \n \n      \n     \n   \n    \n    \n \n \n \n      \n     \n \n   \n     \n \n  \n  \n    \n  \n   \n \n \n \n  \n  \n  \n  \n    \n    \n   \n  \n         \n    \n  \n  FRIDAY : SEPTEMBER 22 , 2023  \nWELCOME AND INTRODUCTIONS \nCall to Order/Roll Call \nDr. Grace Lee (ACIP Chair) called to order and presided over the September 22, 2023 \nAdvisory Committee on Immunization Practices (ACIP ) meeting. Dr. Lee conducted a roll call, \nwhich established that a quorum was present. A list of Members, Ex Officios , and Liaison \nRepresentatives is included in the appendixes at the end of this summary document. No \nconflict s of interest (COIs) were identified. \nAnnouncements \nDr. Melinda Wharton (ACIP Executive Secretary, CDC) noted that copies of the slides for the \nmeeting were available on the ACIP website and were made available through a ShareLink ™ \nfile for ACIP Voting, Ex O fficios , and Liaisons Members . The ACIP is, at its heart, a public body. \nEngagement with the public and transparency in all of its processes are vital to the committee’s \nwork. She indicated that there would be 1 oral public comment session during this meeting, \nwhich was scheduled for 2:30 PM Eastern Time ( ET). To create a fair and more efficient \nprocess, individuals interested in making an oral comment were asked to submit a request \nonline in advance of the meeting. Priority is given to these advance requests. If more people \nmake requests than can be accommodated, a blind lottery is conducted to determine who the speakers will be. Speakers selected in the lottery for this meeting were notified in advance of \nthe meeting. Members of the public also may submit written comments via \nhttps://w ww.regulations.gov using Docket Number ID CDC- 2023-00 76. Information on the \nwritten public comment process, including information on how to make a comment, can be \nfound on the ACIP website. \nAs noted in the ACIP Policies and Procedures manual, ACIP members agree to forgo \nparticipation in certain activities related to vaccines during their tenure on the committee. For \ncertain other interests that potentially enhance a member’s expertise while serving on the \ncommittee , CDC may issue limited COI waivers. Members who conduct vaccine clinical trials or \nserve on data safety monitoring board s (DSMB s) may present to the committee on matters \nrelated to those vaccines, but those members are prohibited from participating in committee \nvotes on issues related to those vaccines. Regarding other vaccines of the concerned company, \na member may participate in discussions with the provision that he/she abstains on all votes \nrelated to that company. ACIP members state any COIs at the beginning of each meeting. \nApplications and nominations are being accepted for candidates to fill upcoming vacancies on \nthe committee. \n2 \n \n  \n   \n \n \n \n    \n     \n      \n    \n       \n    \n      \n  \n    \n   \n \n  \n   \n    \n  \n    \n \n    \n    \n        \n     \n \n \n  \n \n \n \n  \n  \n \n \n  \n  \n \n       \n   \n  \n   \n  \n     \n   \n  \n \n MATERNAL/PEDIATRIC RESPIRATORY SYNCYTIAL VIRUS (RSV) VACCINES \nSession Introduction \nSarah S. Long, MD (Chair, Maternal/Pediatric RSV WG) reminded everyone that each year in \nthe United States (US) children less than 5 years of age, RSV is associated 100 to 300 deaths,1 \n50,000 to 80,000 hospitalizations,2 approximately 500,000 emergency department (ED) visits ,3 \nand about 1.5 million outpatient visits.3 RSV is the leading cause of hospitalization in US \ninfants .4 Most (68%) infants are infected in the first year of life and nearly all (97%) have been \ninfected by 2 years of age.5 Approximately 2% to 3% of young infants will be hospitalized for \nRSV.6 RSV is the most common cause of lower respiratory tract infection (LRTI) in infants. The \nhighest RSV hospitalization rates occur in the first months of life and risk declines with \nincreasing age in early childhood.7 About 79% of children hospitalized with RSV under 2 years \nof age had no underlying medical conditions,8 which is very important to keep in mind . \nTopics of previous WG presentations to the ACIP regarding RSV prefusion F protein (RSV preF) \nvaccine have included epidemiology and burden of RSV in infants ; virology and immunology of \nRSV; safety and efficacy of RSVpreF; c ost-effectiveness analysis for RSVpreF (CDC model); \ncost-effectiveness analysis for RSVpreF (comparison with the manufacturer model); Evidence to \nRecommendations (EtR) framework for RSVpreF; and clinical considerations for RSVpreF . \nOn August 21, 2023, the Food and Drug Administration (FDA) approved Pfizer ’s RSV preF \nvaccine for use in pregnant people for the prevention of lower risk for RSV lower respiratory \ntract disease (LRTD) and severe LRTD in infants born and from birth to 6 months of age.9 The \nvaccine is approved as a single- dose to begin at 32─ 36 weeks of gestation. In Phase 2b and \nPhase 3 trials , vaccination was given during 24─ 36 weeks gestation . A numerical imbalance in \npreterm births was observed in RSVpreF vaccine compared to placebo recipients in 2 clinical studies. Available data are insufficient to establish or exclude a causal relationship between \npreterm birth and RSVpreF. Additionally, a numerical imbalance in hypertensive disorders of \npregnancy was observed in RSVpreF vaccine compared to placebo recipients. Starting dosing \nat 32 weeks gestation can reduce the potential risk of and complications from preterm birth until \nadditional safety data are available. This avoids the risk of extremely preterm births, where there is substantive morbidity and mortality, and very preterm births. Similar vaccine efficacy (VE) in \n32─36 weeks gestation compared to the overall study population. FDA has required the \nmanufacturer to conduct post -marketing studies to assess preterm birth and hypertensi ve \ndisorders of pregnancy, including pre- eclampsia. \n1 Thompson et al, JAMA, 2003; and Hansen et al, JAMA Network Open, 2022 \n2 Hall et al, NEJM, 2009; and McLaughlin et al, J Infect Dis, 2022 \n3 Hall et al, NEJM, 2009 \n4 Suh et al. JID 2022 \n5 Glezen et al, Arch Dis Child, 1986 \n6 Hall et al, Pediatrics, 2013; Langley & Anderson, PIDJ, 2011; and CDC NVSN data \n7 Hall et al, NEJM, 2009; and CDC NVSN data \n8 Hall et al, NEJM, 2009 \n9 https://www.fda.gov/news- events/press -announcements/fda- approves -first-vaccine -pregnant -individuals -prevent -rsv-infants ; \nhttps://www.fda.gov/media/171482/download?attachment; and https://www.fda.gov/media/171492/download?attachment \n3 \n \n     \n \n  \n      \n  \n  \n \n  \n \n     \n  \n    \n     \n    \n \n \n \n \n \n \n \n \n \n \n \n\n\n\n\n\n\n  \n \n   \n \n    \n   \n \n  \n   \n   \n \n \n  \n \n   \n \n  \n \n    \n     \n    \n   \n  \n   \n  \n   \n  \n \n   RSVpreF vaccine is one of two available preventive products for RSV in infants. On August 3, 2023, ACIP recommended nirsevimab for RSV prevention in infants . Infants aged <8 months \nborn during or entering their first RSV season are recommended to receive 1 dose of \nnirsevimab (50 mg for infants <5 kg and 100 mg for infants ≥5 kg). Children 8 ─19 months of age \nwho are at increased risk of severe RSV disease and en tering their second RSV season are \nrecommended to receive 1 dose of nirsevimab (200 mg) . \nBoth nirsevimab and maternal RSV vaccine provide passive immunity .\n10 A person develops \nactive immunity from infection or vaccination, which triggers an immune respons e. Immunologic \nmemory provides prolonged protection that may be lifelong. Passive immunity is the transfer of \npreformed antibody produced externally to provide protection to the recipient, such as from mother to baby through transplacental or breastmilk transfer; or through direct administration of \nantibodies, such as i ntravenous immunoglobulin (IVIG) t herapy or monoclonal antibodies. \nPassive immunity provides temporary protection that wanes with time. \nThis meeting included presentations on the following: \nRSVpreF Vaccine Safety Surveillance in Pregnancy from The Vaccine Safety Datalink \n(VSD) \nMaternal RSV Vaccine Safety Monitoring in the Vaccine Adverse Event Reporting System \n(VAERS) and v -safe\nsm \nAn Economic Analy sis of RSVpreF Maternal Vaccination \nEconomics of Preventing RSV Disease among US Infants by Maternal Vaccination Prior to \nBirth \nEtR Framework Updates: Pfizer Maternal RSVpreF Vaccine Updated Clinical Considerations for Use of Both Nirsevimab and Pfizer RSVpreF V accine \nImplementation Considerations for Maternal RSV Vaccine \nVaccines for Childrens Resolution \nIn closing, Dr. Long presented the Policy Question under consideration: \n“Should Pfizer RSVpreF vaccine be recommended for pregnant people to be given during 32 \nthrough 36 weeks gestation to prevent RSV lower respiratory tract infection in infants?” \nRSVpreF Vaccine Safety Surveillance in Pregnancy from the VSD \nMalini DeSilva, MD, MPH (HealthPartners Institute) reminded everyone that the VSD is a \ncollaborative project between CDC ’s Immunization Safety Office (ISO) and integrat ed health \ncare organizations in the US. The VSD monitors the safety of vaccines used in the US through \nreal-world data of rare and serious events following vaccination. The project includes data on \napproximatel y 15.5 million individuals across all sites annually, with approximately 115,000 \nannual live births. Data are organized using a common data model with standardized coding \nsystems. There are 13 VSD sites across the country that provide clinical, methodological, and data expertise, 11 of which provide data for the project . \n10 https://www.cdc.gov/vaccines/vac -gen/immunity -types.htm \n4 \n \n   \n  \n     \n      \n     \n  \n     \n    \n   \n  \n   \n \n  \n    \n   \n    \n    \n    \n    \n     \n   \n  \n \n    \n    \n     \n      \n       \n  \n    \n   \n    \n     \n  \n \n \n  \n  \n  \n     \n   \n      \n    \n   \n   \n    \n  \n  The VSD’s data structure is based on a distributed data model in which each VSD site creates \nstandardized data files used in multi- site studies. Each VSD site defines a cohort for inclusi on \nbased on enrollment in the site’ s health plan and/or care received at the VSD site. Once a \ncohort has been defined, files for vaccine administrations, medical diagnoses, and procedures \nfrom inpatient , outpatient, and ED visits and birth and death files are created. The dynamic \npregnancy episode files uses validated algorithms for identifying ongoing and completed \npregnancies. This file is updated weekly. Information in this file includes the pregnancy start \ndate, or last menstrual period (LMP), gestational age of the pregnancy, and pregnancy \noutcomes when available. A mom baby linkage file allows for evaluation of infant outcomes \nfollowing prenatal vaccinations. Ancillary drug or laboratory files are available on an ad hoc \nbasis for specific studies . Automated data files are supplemented with chart reviews as needed. \nThe VSD has been evaluating the safety of vaccines administered during pregnancy for more \nthan 10 years. The RSV preF vaccine manufactured by Pfizer has been shown to be effective \nagainst severe RSV -associated LRTIs in infants. RSV preF clinical trial data on safety in \npregnant persons identified injection site pain as the most common reactogenicity event and \nidentif ied an imbalance in preterm births in the vaccinated group. Most preterm births are late \npreterm, meaning they occurred at 34 to less than 37 weeks gestation, and most occurred more \nthan 30 days after receipt of the RSVp reF vaccine. Preterm birth imbalance was most prominent \nin a single country. Of note, GSK also was working on an RSV preF prenatal vaccine, but the \nclinical trials halted due to an imbalance in preterm birth in the vaccinated population. The \netiology for preterm birth associated with RSV prenatal vaccine is unknown. \nThe goal of prenatal RSV vaccine surveillance is to evaluate the safety of RSV preF vaccine \nadministered during pregnancy in the VSD ’s large real -world population. Challenges are that as \nvaccine uptake is unknown , which makes it difficult to provide any power estimates. Additionall y, \nthere may be healthy vaccin ee bias, meaning that healthier individuals or those with lower risk \npregnancies may be the first to be vaccinated. This is considered in the analyses and when \ninterpreting results. There is uncertainty regarding recommendations for RSVpreF use in \nadministration of this vaccine, which may impact who receives the vaccine. If persons at higher \nrisk for preterm delivery are recommended to receive RSV preF early in the vaccination window, \nmore preterm births may be identified the vaccinated group. Alternatively, these individuals may \nbe counseled to not receive the vaccine and wait to have their infant receive n irsevimab. The \ntiming of administration during pregnancy overlaps with Tdap recommendations and vaccine \nadministrations are also likely to overlap with influenza and COVID -19 vaccines. \nTo review the pregnancy outcomes and expected timing for the RSVp reF vaccine during \npregnancy , pregnancies are considered “ non-viable ” prior to 20 weeks gestation, “periviable” \nfrom and from 20 through 26 weeks (e.g., meaning there is a reasonable chance of extra uterine \nsurvival ), “preterm” if the pregnancy end s in a live birth before 37 weeks gestation, and “term” if \nthe pregnancy ends in a live birth at gestational age 37 weeks or thereafter . Intrauterine fetal \ndemise outcomes (IFDOs) include spontaneous abortions that can occur up to 20 weeks \ngestational age, or a stillbirth that occurs at 20 weeks gestation or later. The yellow box in the \nfollowing diagram shows the time period during pregnancy when the RSV preF vaccine has \nbeen approved for use. When considering pregnancy outcomes and the RSV preF vaccine, only \noutcomes that are possible will be included. Spontaneous abortion is not a possible outcome \nbecause of t he timing of vaccine and pregnancy : \n5 \n \n  \n \n   \n    \n  \n \n     \n     \n      \n    \n    \n      \n \n \n    \n    \n  \n    \n  \n    \n  \n   \n  \n \n \n \n  \n     \n   \n  \n    \n  \n    \n \nThe primary approach for prenatal RSV preF surveillance will be through bimonthly surveillance. \nValidated algorithms will be applied to electronic health data in the VSD population to identify \npregnant persons 16─ 49 years of age at ≥20 weeks gestation. Excluded pregnancies include \nthose that end in therapeutic abortion, multiple gestation pregnancies, and those with \ninsufficient information to determine the start date of the pregnancy. The exposure being \nevaluated is RSV preF vaccination at or after 28 weeks gestation. This is to account for any \ninaccuracies in gestational age estimation. Pregnant persons vaccinated with RSVpreF are \nmatched to pregnant persons unvaccinated 1:1 based on VSD site and gestational age at \nvaccination. Propensity scores were created to account for confounding using readily available \nvariables (e.g., pregnant person’ s age, pregnancy start date, race, ethnicity , and medical \ncomorbidities ). \nAdverse outcomes evaluated include a cute outcomes and pregnancy -related and birth \noutcomes. These outcomes were chosen based on biologic plausibility and data from clinical \ntrials, as well as being used in prior vaccine safety studies. To identify these outcomes, an \nalgorithm will be used that wa s developed for other VSD safety surveillance work, which has \nbeen modified for a pregnant population. The algorithm uses diagnoses associated with \noutpatient , ED, and hospital encounters. Chart confirmation will be used for selected outcomes. \nThe pregnanc y-related and birth outcomes that will be evaluated include preeclampsia or \neclampsia based on International Classification of Diseases (ICD)- 10 codes, preterm birth \nbased on the gestational age at birth, and stillbirth identified from ICD -10 codes with c hart-\nreviewed confirmation. \nThe next 2 tables show the acute outcomes that will be monitored following vaccination, the risk \nwindow for which each outcome will be evaluated, and the VSD background rate per 10,000. \nThese background rates are based on data f rom COVID -19 studies using the rate in the \nunvaccinated group. In the first table, the risk window for anaphylaxis is limited to the day of and \nfirst day following vaccination and will be studied only in the vaccinated group. The next 3 \noutcomes (fever, malaise/ fatigue, and skin and soft tissue or local allergic reactions ) are limited \nto 7 days following vaccination. All other outcomes listed alphabetically will be evaluated during \nthe 1─21 days and 1─ 42 days following vaccination. The second table is a continuation of the \nfirst. \n6 \n \n  \n \n \n \n       \n   \n  \n    \n      \n  \n \n \n    \n \n  \n    \n    \n     \n  \n \nThe next table shows the pregnancy -related and birth outcomes that will be evaluated, the \noutcome is listed in the left column, followed by the risk window during which each outcome will \nbe evaluated, and the number and percentage of vaccinated clinical trial participants who \nexperienced the outcome from the Phase 3 RSVpreF clinical trial. The outcomes that will be \nevaluated are preeclampsia and eclampsia, preterm b irth, and stillbirth at 1─21 days and 1─42 \ndays . \n¥ RSVPreF Phase 3 clinical trial: Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants | NEJM \n∆Preterm birth rate in high- income countries (Slide 23 Evidence to Recommendations Framework: (cdc.gov)) \nThe risk window for preterm birth will vary based on the age of vaccination and will end up to 37 \nweeks gestation, given that births after 37 weeks gestation are considered term. The \npercentages shown for the RSVp reF Phase 3 trial are based on all study participants for \npreeclampsia and eclampsia and stillbirth. For preterm birth, the rate was used from high-\nincome countries since this seemed most applicable to the VSD population. \n7 \n \n      \n   \n   \n     \n   \n       \n   \n    \n  \n \n   \n      \n    \n   \n \n  \n \n   \n      \n    \n       \n      \n    \n    \n \n \n   \n  \n  \n    \n   \n    \n   \n    \n   \n \n   \n  \n \n     \n  \n  \n     \n    \n  \n  \n \n     For the analysis, risk ratios will be determined with corresponding 95% confidence intervals \nusing Poisson distribution with robust variance using a generalized estimating equation (GEE) . \nCensoring within risk windows will be applied when an individual is no longer at risk for the \nevent, due to pregnancy outcomes that occur, or if an unvaccinated match is vaccinated. \nAdjustments will be included for known confounders . If a preterm birth signal is detected, further \nexploration into the etiology will be performed. A sensitivity analysis will be performed using \nalternative matching strategies. Because the RSV preF vaccine is recommended for use during \nthe same time period when Tdap is recommended, an assessment we will be done to explore \nwhether it is possible to evaluate coadministration of Tdap and RSV preF. \nIn terms of an example timeline for the planned bimonthly surveillance, i f vaccination started in \nOctober 2023 , the plan would be to capture 2 months of vaccinations followed by a 42- day \nfollow- up period and a 2- month data lag before pulling any data. The first data pull would be in \nMarch 2024. Bimonthly surveillance would continue every 2 months. \nMaternal RSV Vaccine Safety Monitoring in VAERS and v -safesm \nPedro L. Moro, MD , MPH (CDC/NCEZID) described maternal RSV vaccine safety monitoring in \nVAERS and v -safesm. As a reminder, VAERS is a national passive surveillance system that is \nthe frontline surveillance system that monitors all licensed vaccines in the US. Created in 1990, \nVAERS is co-managed by the CDC and FDA. A couple of the important s trengths of VAERS are \nthat it can rapidly detect safety signals and it can detect rare adverse events (AEs) . However, \none of its important limitations is that it is not designed to assess causality. VAERS is a \nhypothesis -generating system that can identify potential vaccine safety concerns that can be \nstudied in more robust systems. \nIn terms of some of the approaches that can be used to analyze various data in pregnancy \nreports , VAERS has been used for more than a decade as part of vaccine safety surveillance \nfor vaccines used in pregnancy (e.g., influenza, Tdap, COVID -19). One type of analysis that can \nbe performed using VAERS data is a descriptive analysis, which includes clinical review of \nindividual reports , aggregate descriptions of automated data (e.g., counts of reported AEs).11 \nAnother is calculation of reporting rates for pregnancy outcomes if doses of RSV vaccine administered in pregnancy or vaccination coverage data are available. Regarding the statistical \nanalyses that may be done, historical approaches have included data mining to assess for \ndisproportionate reporting. This is under discussion for RSV vaccines. \nThe search for RSV pregnancy reports involves  a number of strategies . One strategy is to \nsearch Medical Dictionary for Regulatory Activities (MedDRA) codes for the specific terms: \nexposure during pregnancy, drug exposure during pregnancy, maternal exposure during \npregnancy.  Another approach is t o search for an affirmative answer to Question 8 that asks the \npatient whether they were pregnant at the time of vaccination. In addition, a string search can \nbe done of text fields (e.g., symptoms, pre -existing illness, medical history ) for the term “preg .” \nMedical records will be requested for all pregnancy reports, including serious and non -serious. \nClinicians will review these reports to confirm that they are pregnancy reports and to categorize \nthe main AE of interest. \n11 Reported adverse events are coded using Medical Dictionary for Regulatory Activities terms ( https://www.meddra.org/ ) \n8 \n \n      \n      \n    \n   \n  \n  \n  \n     \n    \n \n \n \n \n    \n \n \n \n \n \n \n \n \n \n \n\n\n\n\n\n \n \n  \n \n \n \n \n \n \n         \n    \n      \n        \n      \n   \n     \n  \n  \n \n      \n   VAERS will conduct surveillance of adverse events of special interest (AESIs) after RSV \nvaccination. Primary AESIs have been selected for historical , theoretical, or observed safety \nconcerns (i.e., in clinical trials) . VAERS will obtain medical records for all reports (serious12 and \nnon-serious) . CDC will review records and abstract clinically important information. AESIs may \nbe added to or removed from the list as appropriate. Secondary AESIs will be monitored via periodic (e.g., weekly) automated data tables, but the information will not be abstracted. If a secondary AESI is identified that is being reported frequently under suspicion of a safety \nconcern, that may be added to the primary AESI list. The current listing of primary and \nsecondary AESIs that will be monitored in VAERS for all RSV vaccines, including for reports \namong pregnant persons, are as follows: \nPregnancy -specific  outcomes to be monitored in VAERS and abstracted after maternal RSV \nvaccine include: \nPremature/preterm birth \nStillbirth \nSpontaneous abortion \nGestational diabetes \nPreeclampsia/eclampsia/gestational hypertension \nBirth defects \nMaternal and infant deaths \nOther selected adverse infant outcomes/AEs \nDevelopment of a new version of v-safesm began in Summer 2023. This system leverages the \nexisting CDC IT infrastructure and includes e- mail and text messaging options . The first use will \nbe for RSV vaccines received by persons ≥60 years of age in the Fall . Use for maternal RSV \nvaccines is planned for later in the Fall. The v-safesm objectives are to: 1) characteriz e local and \nsystemic reactogenicity during day s 0─7 zero to seven after vaccination; 2) characterize health \nimpacts during a 6-week post -vaccination follow -up period; and 3) identify participants who \nreport medically -attended events after vaccination and encourage completion of  a VAERS \nreport. \n12 Based on the Code of Federal Regulations if one of the following is reported: death, life-threatening illness, hospitalization or \nprolongation of hospitalization, permanent disability, congenital anomaly or birth defect \n9 \n \n  \n \n   \n \n     \n   \n    \n      \n     \n     \n     \n     \n    \n       \n   \n   \n    \n    \n \n   \n      \n  \n \n  \n     \n      \n    \n   \n  \n     \n     \n \n     \n     \n       \n       \n  \n       \n     \n        \n       \n   \n \n     \n \n   \n  \n      \n    \n \n   An Economic Analysis of RSVpreF Maternal Vaccination \nDavid W. Hutton, PhD, MS (University of Michigan) provided some updates since his June \n2023 presentation to the ACIP to report the findings of an additional vaccine efficacy scenario, \nadditional timing scenarios for which the vaccine might be administered in specific months of the \nyear, a gestation scenario from 32─36 weeks,  and an updated cost per vaccine dose scenario. \nThe initial efficacy scenario has not changed,13 with sigmoid downward sloping efficacy during \nthe 6 months, using the average efficacy during these periods based on average 6 months \nefficacy. Hospitalization efficacy was based on hospitalization efficacy from the trial and efficacy \nagainst outpatient visits was based on efficacy and medically -attended LRTIs . A scenario also \nwas evaluated with flat efficacy during those 6 months, and then back down to 0 efficacy after \nthat. In both of the last 2 scenarios, 0 efficacy was assumed after 6 months. The new scenario \nis more optimistic, with slightly higher efficacy in the first 6 months. The efficacy against \nhospitalization in this scenario was based on efficacy against severe -medically attended RSV \nLRTI observed in the trial , which was slightly than the efficacy used in the base-case. In this \noptimistic scenario, it was assumed that there is declining efficacy for months 6─9. \nIn the initial base- case, RSV preF given year -round was evaluated. The new scenarios assessed \ncost- effectiveness if RSV preF is given during specific months of the year and if RSVpreF is \nadministered in specific ranges of months throughout the year : April- February , May-February , \nJune- February , August -January , September -January , and September -December . Another \nchange was a scenario in which the mother was vaccinated from the beginning of week 32 \nthrough the end of week 36 of the pregnancy , which is a narrower range than was used in the \ntrial but is what the FDA has settled on. In the new scenario, it was assumed that the vaccine \nmust be given within 2 weeks before birth for the vaccine to confer protection. It was assumed \nthat for a baby born within 2 weeks of administration, the re would be no efficacy of the vaccine. \nIf it is assumed that for 100 pregnant persons, 50 intend to vaccinate, 48 actually get vaccinated \nbecause 2 might give birth before that, and 3 of the 48 would be vaccinated within 2 weeks of \ndelivery —that would res ult in 45 being vaccinated in time (e.g., within 2 weeks before delivery) . \nIn June, Dr. Hutton presented numbers based on 1000 births. During this session, he present ed \nthe results based on the entire US birth cohort per year assuming 50% uptake of the RSVpreF \nvaccine across the first RSV season. Another major update for this scenario is a cost of $295 \nper dose. That is an increase from the $200 per dose estimate used in June, which is a \nsignificant increase in the price per dose. In terms of the results,  the number needed to \nvaccinate (NNV) to avoid an outpatient visit (40), an ED visit (115), an inpatient stay (242), an \nICU admission (1100), an inpatient day (45), or an intensive care unit ( ICU) day (367) was very \nsimilar to what was shown in June. It was about 4% higher because of the later timing of \nvaccination in weeks 32 ─36 due to slightly more people being vaccinated within 2 weeks of \nbirth. But basically, this is very similar to what was reported in June. \nIn the updated scenario, the total cost were higher due to evaluating a larger cohort of 3.66 \nmillion births, assuming 50% intended uptake in RSVpreF group. The intervention cost is higher \nrelatively -speaking because the vaccine price per dose increased by just under 50% from the \nprevious scenario. The cost per event averted also was higher than show n in June because the \nprice per dose is a little bit less than 50% higher than what was assumed in June. For example, \nthe cost to avert an inpatient stay would be about $68,000 per inpatient stay averted. The \n13 Kampmann et al 2023 \n10 \n \n         \n     \n  \n \n  \n \n     \n    \n   \n  \n    \n         \n  \n    \n \n  \n   \n \n      \n     \n      \n    \n      \n \n     \n       \n       \n     \n    \n       \n     \n    \n    \n     \n    \n    \n \n  \n       \n    \n     \n     \n     \n \n \n \n  \n \n \n  incremental cost-effectiveness ratio (ICER) in the updated scenario is now about $400,000 per \nquality -adjusted life year (QALY) gained. This is driven primarily by the increased cost of the \nvaccine dose compared to the cost used in June. \nLooking at sensitivity analyses showing how various changes in the assumptions will change \nthe ICER, the rankings of which parameters are most important are similar to those seen in \nJune. Prematurity potentially can increase the ICER dramatically , though hopefully that is less \nlikely with later administration of RSVpreF . The QALY impacts of RSV also are likely to have \nlarge impact on the ICER . The vaccine price is an important driver of cost -effectiveness. The \ncost of inpatient care also can have a large impact on the cost -effectiveness of vaccination. VE \nalso can have a large impact on cost-effectiveness . One of the scenarios was varying how VE \nwas modeled. When flat efficacy was assumed, the ICER was about $365,000 per QALY \ngained. The updated scenario used a m ore optimistic higher and longer efficacy. The ICER \nunder this scenario was about $286,000 per QALY gained. \nIn a sensitivity analysis varying efficacy, hospitalization cost, and mortality the base cost was \n$11,000 per hospitalization. Varying the hospitalization cost from the base cost to higher costs, \nthe cost -effectiveness ratio would decrease as hospitalization costs increase. With a more \noptimistic VE (e.g., higher and longer efficacy ) the cost- benefit ratio would decrease as well. \nWith m ore deadly RSV, there would be a 1% risk of dying in the hospital instead of 0.1%. The \ncost per vaccine dose also can have a major impact on cost -effectiveness. With a base-case \nprice of $295 per dose, the cost per QALY is close to $400,000 . If the vaccine cost per dose \nwas lower, the ICER would decrease as well. \nEverything just show n was assuming the vaccine is given year -round. Now looking by month \nand by specific ranges of months to determine the cost- effectiveness ratio if RSVpreF is given in \na particular month of the year, it is important to remember that RSV is seasonal and there are \nmany infections in the wintertime. If RSVpreF is given right before wintertime so that it has 6 \nmonths of efficacy during that peak, the cost of that administration would decrease dramatically . \nFor instance, if RSVpreF is given during any month between February ─July, the cost -benefit \nratio would be over $500,000 per QALY. If given during October ─November, the cost -\neffectiveness ratio would range from approximately $111,000 to $115,000 per QALY. The cost \nof administration could be dramatically lower if RSVpreF is given right before the peak of the \nRSV season. Looking at ranges of months and recalling that the base -case was about $400,000 \nper QALY if given year-round,  if it was given during the range of September ─December, the \nICER would be approximately $141,000 per QALY. \nTo summarize, the limitations of this updated analysis are similar to the ones reported in June. \nThe model structure does not include risk groups or dynamic transmission. Given that this is a \nnew vaccine, the impact of the vaccine on transmission and indirect effects is unknow. Inputs \nalso are still uncertain with respect to RSVpreF costs , QALYs lost , impact URTIs , and \nprematurity. All of these scenarios assumed that no infants will be receiving nirsevimab. \nRSVpreF may improve RSV outcomes, but it also will increase costs. RSVpreF has the potential \nto be cost -effective , but the results are sensitive to a wide variety of assumptions, including r ate \nof prematurity ; cost per dose (~ $65,000─$68,000/QALY) ; hospitalization costs ( cost-\nsaving─$440,000/QALY) ; efficacy (~ $280,000─$680,000/QALY); QALYs lost \n(~$100,000─$800,000/QALY) ; and m onth of administration (~ $110,000─ Millions/QALY) . \n11 \n \n     \n    \n    \n \n \n \n \n \n  \n   \n   \n \n      \n    \n     \n  \n    \n     \n      \n     \n       \n \n \n     \n      \n   \n    \n     \n  \n \n  \n     \n \n       \n      \n   \n     \n  \n  \n     \n     \n     \n \n \n    \n     \n   \n   \n   \n    \n     \n   \n   Looki\nng now at the economics of the combined use of Pfizer maternal RSVpreF vaccine and \nnirsevimab , ACIP recommended the use of nirsevimab On August 3, 2023. This raises the \nfollowing questions about how to think about combinations of RSVpreF and nirsevimab : \nIf it is known that RSVpreF has been administered to the pregnan t person in time, how cost -\neffective is it also to provide nirsevimab to the infant ? \nIf it is known that the infant definitely will receive nirsevimab, how cost -effective is it to \nprovide RSVpreF to the pregnant person? \nIn terms of updates since the June ACIP meeting, the assumption was made in the updated \nanalysis that RSVpreF would be administered in weeks 32─36. Because of this, the assumption \nalso was made that the infant is full- term and there would be no need for palivizumab for any \nnewborns considered in this analysis. The updated analysis also considered some higher risk \npopulations and assumed that they were not premature. In addition, the new timing of RSVpreF \nadministration was considered. There is no evidence of efficacy with the combined use of these \nproducts. Therefore, the assumption was made that efficacy would be equal to the highest of \nnirsevimab or RSVpreF, which is higher. That is, efficacy would not be higher than from the \nmost effective product and there would be no combined synergistic efficacy. That is the same \nassumption that was made in June. \nAssuming administration of nirsevimab at birth to the infant of someone who received RSVpreF , \nnirsevimab would provide additional efficacy on top of what RSVpreF would provide. If the baby \nwas born in August, they would have some RSVpreF efficacy. If nirsevimab was given on top of \nthat in October, there would be an increase in efficacy. A s a reminder, peak infections are \ntypically in the December ─February timeframe, and additional efficacy would be desired during \nthat peak timeframe. \nTo highlight the incremental benefit of adding nirsevimab on top of RSVpreF for infants of \npersons vaccinated with RSVpreF during pregnancy at least 2 weeks prior to delivery , there \nwould be a higher risk or increased multiplier on the risk of hospitalization. There would be no \nchange in outpatient incidence, ED inciden ce, costs per outcome, or QALY per outcome. \nLooking at the incremental benefit of adding nirsevimab on top of RSVpreF by m onth and risk if \nnirsevimab is given at birth during October ─March compared to a baby born in \nApril─September who would not be given nirsevimab at birth but would receive it at the start of \nthe RSV season in October or November , the incremental cost-effectiveness of adding \nnirsevimab looks better if given to babies born in April, May, June, July, August, and September. \nIf given at the beginning of the season in October and November, the cost- effectiveness ratios \nwould be much lower. The ICERs are much higher for infants who are at 3-, 6-, and 10 -times \nhigher risk of hospitalization. That is, it is much more valuable to give them nirsevimab on top of \nRSVpreF . \nParticularly for babies born in the summer, giving nirsevimab at the beginning of the season \nwould result in an ICER $150,000 per QALY gained and lower . For potentially higher risk \nindividual s born during the season, the ICERs for n irsevimab given at birth might look good for \nhigher risk populations. Assuming that nirsevimab is given to all infants born year -round to \nvaccinated mothers, the NNV to avoid an inpatient visit for an average risk child would be over \n200 infants to avoid 1 inpatient visit. Adding nirsevimab to all infants born year -round to \nvaccinated mot hers would be quite expensive for people at average risk at $400,000 per QALY . \nProviding nirsevimab to infants at 6 times the risk born to vaccinated mothers would be about \n$40,000 per QALY gained and might be cost -effective . \n12 \n \n  \n    \n     \n   \n    \n     \n  \n     \n     \n  \n   \n \n    \n      \n     \n  \n    \n     \n       \n      \n   \n   \n \n  \n   \n     \n    \n     \n \n \n \n \n     \n      \n      \n       \n         \n    \n     \n \n      \n   \n  \n  \n   \n \n     \n   \n     \n   \n In a scenario of giving nirsevimab in October ─November to babies born in April─ September, \nrather than at birth, born to mothers who received RSVpreF at least 2 weeks prior to delivery, \nthe NNV was similar but slightly lower than if giving n irsevimab year -round. It would be more \ncost- effective to provide nirsevimab to infants born since April─ September at the beginning of \nthe RSV season at about $300,000 per QALY for infants at the lowest risk and about $200,000 \nper QALY for infants at 3-, 6-, and 10- times higher risk. In a scenario of adding nirsevimab \nduring the season for infants born October─March to mothers who received RSVpreF at least 2 \nweeks prior to delivery, the NNV would be higher because they already would have a lot of \nRSVpreF protection during that time period. The ICER would be $600,000 per QALY if given to \naverage risk babies. That is, it would be less cost -effective to give these babies nirsevimab on \ntop of their RSVpreF protection. \nRegarding the incremental benefit of adding n irsevimab on top of a baby’s RSVpreF protection, \nthere is some additional benefit beyond RSVpreF protection. The ICERs are high, but could be \nlower for higher -risk populations, particularly born if they are born off -peak. In terms of the \nincremental benefit of adding RSVpreF on top of nirsevimab if it is known the infant will be \nreceiving nirsevimab, the ICERs are very high. Similar to what was seen previously, this scenario would be over $10 million per QALY for many months of the year . The best month of \nthe year would be April, although the ICER still would be $2.4 million per QALY gained if \nnirsevimab was given to babies whose mothers received RSVpreF at least 2 weeks prior to \ndelivery . The incremental benefit of adding RSVpreF on top of nirsevimab would be very \nmarg inal beyond nirsevimab protection and the ICERs would be extremely high. \nIn summary of scenarios involving combinations of RSVpreF on top of nirsevimab, a limitation is \nthat there are no efficacy data on these combined products. Therefore, these scenarios are all \nbased on assumptions about what the efficacy might be. Nirsevimab may add additional \nprotection on top of RSVpreF , particularly for high -risk infants . Adding RSVpreF on top of \nNirsevimab would add marginal effectiveness at a very high cost in the general population. \nEconomics of Preventing RSV Disease among US Infants by Maternal Vaccination Prior\nto Birth \nIsmael R. Ortega- Sanchez, PhD (CDC/NCIRD) summarize d the key elements and findings of \n2 economic studies , the Pfizer Model and the University of Michigan- CDC ( UM-CDC) M odel, \nfocused on the economics of preventing RSV disease among US infants by maternal \nvaccination prior to birth. In the last 8 to 9 months, the 2 models were updated several times. In \nthis summary, Dr. Ortega -Sanchez focused only on the vaccine so there was no discussion \nabout the last component of Dr. Hutton’s presentation regarding nirsevimab . For full disclosure, \nDr. Ortega -Sanchez indicated that he has been part of the team conducting the CDC model. \nThe starting point of the 2 economic models was the policy question regarding potential \nrecommendations for the use of RSV vaccine in pregnant mothers , “Should Pfizer RSVpreF \nvaccine be recommended for pregnant mothers to be given during 32 through 36 weeks \ngestation to prevent RSV lower respiratory tract infection in infants?” To consider the economics \nof the policy question is to consider simultaneously the health benefits and costs of vaccination, \nnamely, “Is vaccinating pregnant mothers prior to birth to protect infants against RSV ’s cost -\neffective?” To address this question, the 2 models used the same comparator , unvaccinated \nmothers and the standard of care (SoC) for infants. They focused on analyzing the cost -\neffectiveness of vaccinating pregnant mothers 32 ─36 weeks of gestation ≥2 or more weeks \nprior to the birth with RSV preF vaccine compared to no vaccine. \n13 \n \n     \n     \n     \n     \n  \n     \n   \n     \n       \n \n   \n   \n        \n \n \n \n     \n  \n \n   \n        \n    \n      \n    \n     \n      \n    \n    \n      \n     \n    \n      \n    \n      \n     The policy question has important implications for 2 groups of elements . The comparison of the \n2 economic models focus es on the appropriateness of the modeling approach selected; the \ninputs for RSV disease burden, RSVpreF, VE, and costs ; and how the strength and influence of \nthe assumptions on the outcomes. The 2 models followed similar designs. Both used a static \nanalytical decision- making approach , relied on sensitivity analys es and probabilistic simulation, \nmodel ed a hypothetical cohort of all pregnant mothers in the US year-round, selected a \ntimeframe of the first year after birth, accounted for loss of income associated with temporary \nproductivity loss and the loss of premature RSV -associated infant mortality. Once the modeling \nstudy was set, the 2 models were fed by different types of input data, including clinical, \nepidemiological, economic, QALY, vaccine characteristics, health care resource utilization \n(HCRU) and cost, and indirect costs . Across models, the source and specific values and \nassumptions of these parameters have some overlaps, but there were marked differences as \nwell. The boxes below list the standard outcomes estimated and reported by the 2 models : \nDr. Ortega -Sanchez emphasized that once the models are built this way, it is necessary to work \nin reverse in order to go first with the outcomes and then analyze what happens with the inputs. \nThe base case estimate for vaccinating pregnant mothers in the vaccination window of 32 ─36 \nweeks gestational age year-round would be approximately $400,000 per QALY gained when \nvaccine costs are $295 per dose. Additionally, the CDC model reports cost per specific type of \nhealth outcome prevented and the NNV to prevent hospitalization , ED visits, outpatient visits, \nand deaths associated with RSV LRTI . the base case estimate for maternal vaccination in the \nvaccination window of 32─36 weeks gestational age year -round would be approximately \n$85,000 per QALY gained when vaccine cost is $295 per dose. The Pfizer cost per QALY is \nsupported wit h its probabilistic sensitivity analysis (PSA) when simultaneously providing the \ninput and variables in the model. Most of the simulations included in the base case were \nsomewhat costly, but with gains in QALY. Approximately 65% of the simulations in the P fizer \nmodel had a cost -effectiveness ratio that was less than $100,000 per QALY . Even though both \nmodels assumed the same vaccine cost per dose, vaccination window of 32─ 36 weeks of \ngestational age, and year-round vaccination administration, the CDC results costs per QALY \nwere still much higher than those of Pfizer. Specifically, the CDC estimates of the cost per \nQALY and the cost per hospitalization of births were about 5 times higher than those of Pfiz er \nand about 10 times higher for the cost per death prevented. The CDC model report ed a 65% \n14 \n \n     \n      \n    \n \n \n    \n    \n      \n    \n       \n   \n   \n   \n \n \n \n \n  \n  \n \n \n  \n \n  \n \n     \n     \n    \n   \n     \n    \n    \n \n        \n       \n      \n    \n       \n   \n \n \n  \n \n \n      \n      \n       \n        \n    \n    \n     \n \n    higher NNV to prevent hospitalization and 300% higher in the number needed to prevent an \nRSV-associated death. The first takeaway for the committee is that both models agree that \nmaternal vaccination will be relatively costly, but it also will prevent LRTI and hospitalization and \nwill save QALY s among infants and caregivers. \nTo understand these persistent discrepancies in the UM -CDC model and the Pfizer model , an \neffort was made to i dentify the sources of these differences. The CDC model’s 1 -way sensitivity \nanalysis ranked the most influential input variables. The probability of prematurity ranks first, \nfollowed by RSV QALYs lost , disease -specific inpatient cost, and VE against hospitalization. In \na similar fashion, Pfizer also report ed one -way sensitivity analy ses. T he most influential \nvariables were VE , followed by medical costs for hospitalization, vaccine duration of protection \nwhen truncated at 6 months, and the case fatality rate among hospitalized infants with RSV \nLRTI. Except for RSV hospitalization risk and seasonality and vaccine- associated AEs, the \nother elements identified in the Pfizer and UM -CDC models included, which were explored \nfurther : \nVaccine efficacy Duration of protection and waning RSV Case fatality rate \nMedical cost of RSV hospitalization, ED and Outpatient care QALYs lost by patients and caregivers \nFirst, 2 elements that did not explain these differences were the risk of hospitalization and RSV \nseasonality as input data used in both model s were practically the same. Specifically, the risk of \nRSV hospitalization data used in both models was based on laborator y-confirmed RSV -\nassociated hospitalization by age in months from the New Vaccine Surveillance Network \n(NVSN). This includes only RSV cases that manifests as LRTI. Therefore, unlike the uncertainty \nin RSV hospitalization that was a question for discussion for older adults, it is not what could \nexplain the difference in outcomes in infants . Likewise, RSV seasonality was based on data \nfrom the National Respiratory and Enteric Virus Surveillance System (NREVSS) . The 2 main \nexplanatory factors turn out to be VE and case definition. Although both models use the same \nsource for VE,\n14 which reports the data from the P hase 3 clinical trials from Pfizer , each model \npicked different data points from this source mainly because none of the Pfizer Phase 2 \nendpoint definitions overlap ideally with a case definition used by the US burden data. For \nhospitalizations, the CDC model used average VE over months 0─6 reported by RSV LRTI \nhospitalization, with an average value of 56.8%. The Pfizer model used VE for severe RS V-\npositive MA -LTRI as a proxy for VE against RSV -LRTI requiring hospitalization, and efficacy \nagainst RSV -positive MA -LRTI was used as a proxy for VE against RSV -LRTI treated in the ED. \nVE for late preterm infants was assumed to be 83.3% of corresponding values for full- term \ninfants. \nThis also will help to understand the duration of protection. Although assessing the difference \nabout the initial VE is important, it is more about the assumption of performance over time. In \nthe Pfizer model, the linear assumption was based on 4 data endpoints reported from Phase 3 \ndata until 180 days after vaccinat ion, or the equivalent of 6 months, followed by the assumed \nimpact from the 6th to the 9th month. That is discriminated by a full -term versus late -term. The \nCDC model use d a 6-month efficacy against hospitalization or MA RSV-associated RTI. The \nduration of protection reached 0 at 6 months . They noted a higher level of uncertainty of the \n14 Kampmann et al New England Journal of Medicine. 2023 Apr \n15 \n \n      \n     \n \n   \n     \n      \n     \n     \n      \n \n      \n  \n    \n   \n \n    \n    \n    \n   \n        \n      \n     \n  \n \n  \n     \n        \n \n      \n    \n   \n \n      \n    \n   \n     \n      \n  \n     \n     \n      \n   \n        \n     \n    \n     \n      \n \n  waning assumption beyond available Phase 2 data. The CDC model trie d to minimize this \nuncert ainty impact  on its outcomes. Therefore, there was no effectiveness after the 6th month. \nAlthough the base- case case fatality rate s for hospitalization were basically the same in both \nmodels, the distinction is that Pfizer inputs used a higher case fatality rate for late preterms \nusing mortality rates for all pre- terms. Therefore, the same rate included for extremely early, \nearly , and late preterms were used as the dominator for the case fatality rate for all preterms. \nRegarding medical costs, the input values using the Pfizer model were 2 times higher for \nhospitalization to about 4 times higher for ED and outpatient visits than the ranges used by the \nCDC model to reach the average cost value using. While the source of t he CDC model is a \npublicly available meta- analysis review of many publications. The source of the Pfizer model is \nreported as data on file and not yet available for examination. The committee members should \nbear in mind that the higher the input values , the lower the ICER would be, or the equivalent, \nthe more cost -effective the vaccination program would be. \nCost-effective analysis programs should include not only the cost of vaccines or vaccine \nadministration, but also the risk of vaccine- associated AEs and associated costs. Using data \nreported from the Pfizer P hase 3 trial , both models included the rate of injection site reactions \nand associated costs, including the cost of outpatient visits. The difference was when dealing \nwith hypothetical serious adverse events ( SAEs ) or when considering the incremental risk of \nprematurity . The potential increased risk of AEs considered in the CDC model, when modeled in \nthe base case or as a potential scenario could influence the ICERs and significantly increas e \nthe cost of the intervention. \nIn terms of the QALY impact of RSV outcomes in both patients and caregivers , the point \nestimates scores used in both models were the same for the caregivers. The difference was in \nthe patient scores, which were somewhat higher in the CDC model. The second difference was \nthat the CDC model also relied on ranges from each of these scores, which allowed for the \nanalysis and sensitivity analysis of the impact of them. Unlike CDC, the Pfizer model consider ed \nonly the point estimate f or the base case without viability, and as a consequence quality loss \nwas not identified as an influential variable in the Pfizer model . \nUp to this point, the comparisons focus ed on the inputs used in the models. The idea at this \npoint was to determine how sizeable differences in cost per QALY could be explained from \noutcomes estimated using different input values and assumptions. One way to cross -validate \nthe models is to see if one model could imitate the other by selecting some input values and \nassumptions. Looking at the cost per QALY for selected scenarios using a CDC model focusing \non combining Scenarios A (c ost of RSV -LRTI hospitalization: $20,000 or $50,000) and B ( UM-\nCDC model with same VE duration of protection as Pfizer) that included price, medical costs, \nand assumptions of duration of protection, the specific impact on the cost per QALY drops to \n$234,000 per QALY. That is still 2 times higher than the cost per QALY reported by Pfizer. Two \nother important scenarios reported were Scenario E with a potential increase in the risk of \nprematurity in 1% or 2% points, which could range from about $900,000 if it is only 1% point \nincrease in the risk of prematurity to more than $1.3 million per QALY if it is a 2% point incr ease \nin the risk of prematurity. Scenario F deals with the timing of vaccination. CDC is the only model \nthat present ed timing of vaccination. Vaccinating mothers with births in September ─January \nwould provide a cost per QALY of less than $200,000 as opposed to February ─July, which will \nbe in the millions per QALY. \n16 \n \n   \n     \n    \n      \n   \n    \n      \n  \n  \n    \n \n \n   \n   \n     \n   \n     \n     \n  \n  \n \n   \n    \n      \n     \n  \n     \n   \n  \n    \n   \n    \n  \n \n \n  \n \n   \n    \n   \n   \n   \n    \n     \n   \n  \n   \n    \n \n \n  By the same token, Pfizer attempted to replicate the CDC outcomes by sequentially using CDC \ninputs and assumptions. For Scenario A, the cost per QALY estimate with selected CDC inputs \nand the cost per QALY value were close to what was reported by CDC at approximately 85%. \nScenario A was $343,000 per QALY in the Pfizer model , which was very close to the $400,000 \nper QALY reported by CDC. When Pfizer used its own model with some of the select ed CDC \ninputs and returned most of its own inputs and assumptions piece- by-piece and cumulatively , \nPfizer return ed to his initial VE. It returned to the duration of protection and medical costs that \nPfizer used and to approximately $83,000 per QALY, which is basically the same one that was \nreported by them in the base case scenario. Since they were able to replicate some of the \nanalys es, it seems that the inputs and the assumptions that are being used in the models are \ncrucial. \nIn terms of limitations, the factors not considered may result in overestimating the ICER, under -\nestimating the cost -effectiveness of maternal vaccination, by both models. In the base case, \nboth models assumed no protection against upper respiratory tract infection (URTI), no benefits \nof vaccination for vaccinated pregnant mothers, and no out -of-pocket costs accrued by \ncaregivers during an infant RSV illness. Neither model included RSV-related costs incurred after \ndischarge from RSV -associated hospitalization or ED department v isits, such as p roductivity \nlosses incurred by caregivers after discharge. Both models assumed no indirect effects of \nvaccination (e.g., no protection against RSV transmission among unvaccinated people). \nIn conclusion, difference s in key inputs among the Pfizer and CDC models explain differences in \nthe results. Among the key differences are initial VE and assumptions about protection waning, \nmedical cost data, QALYs associated with RSV LRTI outcomes for patients and caregivers, and \nvaccine- related AEs. In addition, the CDC model identified 2 important factors that could drive \nthe results and make the difference—hy pothetically severe v accine- associated AEs and timing \nof vaccination for RSV when it targeted to specific periods in the RSV season. In terms of the \nbase case in both models, maternal vaccination would significantly reduce RSV disease burden \nand disease costs in infants. Data from clinical trials used in both models support the reduction \nin RSV disease and associated costs. However, the economic value of vaccinating pregnant \npeople to protect infants could increase costs. Reasonable vaccine price and duration of \nprotection, combined with careful design of seasonal interventions , will determine the cost -\neffectiveness value of routine vaccination of pregnant people during the 32─ 36 weeks of \ngestational age. \nEtR Framework Updates: Pfizer Maternal RSVpreF Vaccine \nKatherine E. Fleming -Dutra, MD (CDC/NCIRD) presented EtR Framework updates for the \nPfizer Maternal RSVpreF vaccine. She reminded everyone that the policy question before the \nACIP was, “Should Pfizer RSVpreF vaccine be recommended for pregnant people to be given \nduring 32 through 36 weeks gestation to prevent RSV lower respiratory tract infection in \ninfants ?” Notably, the dosing window represented a change from the policy question discussed \nduring the June ACIP meeting. The reason for this change was because On August 21, 2023,15 \nFDA approved the Pfizer RSVpreF vaccine for use in pregnant people as a single dose to be \ngiven at 32 through 36 weeks gestation. In the Phase 2b and 3 trials, vaccination was given \nduring 24 through 36 weeks gestation. The change was made to avoid the risk of extremely \npreterm births where there is substantive morbidity and mortality and very preterm birt h. FDA \nconsidered that the benefit of vaccine efficacy when the Pfizer RSVpreF vaccine is administered \n15 https://www.fda.gov/news- events/press -announcements/fda- approves -first-vaccine- pregnant -individuals -prevent -rsv-infants ; and \nhttps://www.fda.gov/media/168185/download \n17 \n \n    \n  \n  \n   \n   \n \n   \n   \n     \n    \n  \n      \n     \n  \n \n    \n  \n    \n  \n   \n  \n  \n \n \n      \n    \n  \n    \n   \n \n     \n     \n     \n     \n    \n        \n   \n    \n \n   \n     \n   \n   between 32 and 36 weeks outweighed the risk of vaccination, including the potential risk of \npreterm birth and hypertensive disorders of pregnancy. Throughout the presentation, these \nwere denoted as the approved dosing interval (32 –36 weeks gestation) and the trial dosing \ninterval (24– 36 weeks gestation) . In terms of the PICO question, the intervention was updated \nto reflect the approved dosing interval at 32─36 weeks gestation. Otherwise, the population, \ncomparison, and outcomes remained the same. \nIn terms of the Public Health Problem domain, RSV infection is the leading cause of \nhospitalization in US infants. Most (68%) infants are infected in the first year of life and nearly all \n(97%) by age 2.16 Approximately 2% to 3% of young infants will be hospitalized for RSV.17 RSV \nis a common cause of LRTI in infants. The highest RSV hospitalization rates occur in the first \nmonths of life, all young infants are at risk, and risk declines with increasing age in early \nchildhood.18 Approximately 79% of children hospitalized with RSV who are less than 2 years of \nage had no underlying medical conditions.19 The WG agree unanimously that RSV among \ninfants is of public health importance . \nMoving to the Benefits and H arms domain, the WG had data for all 11 outcomes for the Grading \nof Recommendation Assessment, Development and Evaluation ( GRADE ) for this analysis . Data \nwere available from 2 trials, Pfizer ’s Phase 3 trial and an earlier Phase 2b trial in pregnant \npeople. In terms of how these data were used for GRADE and the benefits and harms domain \noverall, there were data from both trials on the dosing interval and from the FDA approved \ndosing interval. The number of maternal participants by vaccine and placebo arms in the Phase \n2b and Phase 3 are shown in this table: \n*For phase 2b trial and phase 3 trial safety set, number of maternal participants are listed. For phase 3 trial efficacy set, number of \ninfants participants are listed. \n1 Data provided by Pfizer \n2 Kampmann et al. Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants -PubMed (nih.gov) \n3 Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Briefing Document -FDA \nIn both phases, less than half of the maternal participants receive the intervention in the \napproved dosing interval, meaning that the power to assess safety and efficacy was reduced. \nTherefore, for GRADE , the outcomes as assessed in the full trial population with the trial dosing \ninterval of 24 ─36 weeks were used consistent with the trial design. The post-hoc analysis using \ndata from the approved interval was used as supplemental data. To summarize the effect, \nestimates , and concerns in uncertainty of the assessment for the benefits for this vaccine \nassessed at 0─180 days of life, VE against medically attended RSV -associated LRTI in infants \nwas 51%, and efficacy against hospitalization for RSV -associated LRTI in infants was 56.8%. \n16 Suh et al. JID 2022 \n17 Hall et al, Pediatrics, 2013; Langley & Anderson, PIDJ, 2011; and CDC NVSN data \n18 Hall et al, Pediatrics, 2013; and CDC NVSN data \n19 Hall et al, Pediatrics, 2013 \n18 \n \n   \n      \n  \n    \n     \n      \n \n \n   \n      \n     \n   \n   \n    \n   \n    \n  \n \n    \n  \n     \n   \n   \n    \n      \n    \n      \n  \n     \n   \n    \n       \n     \n \n \n    \n   \n    \n  \n     \n   \n  \n \n  \n      \n   \n      \n   \n      \n    \n  Additional data received since June included the important outcomes of ICU admission for RSV \nhospitalization in infants with an efficacy of 42.9% , and mechanical ventilation with an efficacy of \n100%. Both estimates had very wide confidence intervals, and thus the certainty assessments \nwere downgraded due to very serious concerns for imprecision. Additionally, there are now data \nfor all -cause hospitalization for LRTI with an efficacy of 28.9%, with a confidence interval that \ncrossed the null. Therefore, the certainty assessment was downgraded for seri ous concern for \nimprecision. \nRegarding the certainty of assessments for harms, changes from June included the \ndowngrading of 3 outcomes (e.g., SAEs in pregnant people, SAEs in infants, and preterm birth) \nfor serious concerns about indirectness due to the difference in the trial dosing interval \ncompared to the approved dosing interval. This was done because 55% of the Phase 3 trial \npopulation and 62% of the Phase 2b trial populations did not receive vaccine doses during the \napproved dosing interval. There is likely less opportunity for SAEs during pregnancy to occur , \nincluding preterm birth , when dosing starts at 32 weeks gestation as compared to 24 weeks \ngestation. In particular, the risk of preterm birth likely would be lower with dosing starting at 32 \nweeks than with a dosing window that starts at 24 weeks gestation. \nOverall, the summary of GRADE showed that the Pfizer RSV maternal vaccine is effective in \npreventing medically attended RSV -associated LRTI in infants with high certainty in the \nevidence. This vaccine may be effective in preventing hospitalization for RSV -associated LRTI \nin infants , with moderate cert ainty. The vaccine may be effective in preventing ICU admission \nfor RSV hospitalization in infants , with low certainty. The vaccine may be effective in preventing \nmechanical ventilation for RSV hospitalization in infants , with low certainty. The vaccine is not \neffective in preventing all -cause medically attended LRTI in infants , with moderate certainty. The \nvaccine may be effective in preventing all -cause hospitalization for LRTI in infants , with \nmoderate certainty. SAEs in pregnant people were balanced between the vaccine and placebo \ngroups, with low certainty. Reactogenicity in pregnant people was balanced between vaccine \nand placebo groups , with moderate certainty. SAEs in infants were balanced between the \nvaccine and placebo groups , with low certainty . Preterm births were unbalanced between the \nvaccine and placebo groups , with very low certainty in the evidence. This result ed in an overall \nevidence type of “Very Low.” In GRADE , the overall evidence type is driven by the lowest quality \nof evidence for critical outcomes, and here was driven by the evidence rating for the critical \nharm of preterm birth being very low. Comparing the effect estimates for benefits for each of the GRADE outcomes from the full \nPhase 3 trial using the pre- specified trial dosing interval (24–36 weeks gestation) and the \nefficacy estimates for the same outcomes from the Phase 3 trial limited to participants who \nreceived doses during the approved dosing interval (32–36 weeks gestation) , the point \nestimates were relatively similar for each of the outcomes. The confidence intervals were much \nwider when limited to the approved dosing interval, which is to be expected given the smaller \nnumber of participants who received vaccination in the approved dosing interval. \nThe Phase 3 efficacy against severe medically attended RSV -associated LRTI was a co -primary \ntrial endpoint but was not included in GRADE . The reason for this is that this outcome was not \nincluded by the WG as an a priori critical or important outcome for vaccine policy decisions. \nHowever, the WG felt that this was important to present as part of the supplemental data in the \nEtR F ramework. Shown here side- by-side are the Pfizer definitions of severe medically -\nattended RSV LRTI on the left and medically attended RSV LRTI on the right, which was \nincluded by the WG as a critical outcome for GRADE . The differences in these two definitions \nare highlighted in blue: \n19 \n \n  \n  \n  \n \n \n \n  \n    \n      \n  \n   \n     \n  \n   \n   \n \n  \n    \n      \n  \n   \n   \n \n \n \n \n \n       \n      \n   \n    \n \n      \n  \n     \n  \n   \n    \n  \n  \n \n    \n     \n \n    \n    \n     \n     \n  \n   \n   \n   \n \n \n  \n   \n  \n  \n  \n  \n    \n  \n    \n    \n    \n    \n \n   Pfizer Trial Definition WG Definition \nSevere medically -attended RSV -associated LRTI* \nrequired at least 1 of the following signs/ symptoms: \n− Fast breathing (respiratory rate ≥70 (<2 month of \nage [60 days]) or ≥60 (≥2 to 12 months of age) \nbreaths per minute \n− SpO2 measured in room air <93% \n− High -flow nasal cannula or mechanical \n− Ventilation \n− ICU admission for >4 hours \n− Unresponsive/unconscious Medically -attended RSV -associated LRTI* required at \nleast 1 of the following signs/symptoms: \n− Fast breathing: respiratory rate ≥60 (<2 months of \nage [60 days]) or ≥50 (≥2 to 12 months of age) \nbreaths per minute \n− SpO2 measured in room air <95% \n− Chest wall indrawing \n*Medically attended visit includes inpatient and outpatient encounters. Additionally, definition also required RT -PCR or nucleic acid amplification (NAAT) test \npositive for RSV. Blue text denotes differences between the two definitions. SpO2= Peripheral capillary oxygen saturation \n1.Kampmann et al. Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants -PubMed (nih.gov) \n2.Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Briefing Document -FDA \nIn terms of VE against severe medically -attended RSV LRTI in the trial dosing interval and the \napproved interval, at 0─ 180 days after birth efficacy was 69.4% in the full interval and 76.5% in \nthe approved interval. It is important to note t hat not all of the 81 infants who met the severe \nRSV definition within 0─180 days after birth were hospitalized, n or did all infants who were \nhospitalized for RSV meet the severe definition. Comparison for estimates from the full Phase 3 \ntrial dosing interval to the approved dosing interval, the point estimates for relative risk were \nsimilar but the confidence intervals were wider. Specifically for preterm birth, the relative risk in \nthe vaccinated group compared to the placebo group using the full trial dosing interval was 1.20 \nwith a 95% confidence interval of 0.99 to 1.46. The relative risk with the approved dosing \ninterval was 1.15 (0.82, 1.61) with a wider confidence interval consistent with decreased power \nto detect this outcome. The confidence intervals were overlapping between the 2 estimates. \nAs a reminder, the WG chose preterm birth as a critical outcome because a trial for a similar \nGSK maternal RSV vaccine,20 also a stabilized prefusion F- protein vaccine, was halted due to \nan imbalance of preterm births , with higher numbers in the vaccine compared to the placebo \ngroup. In that trial, there also was an imbalance in neonatal deaths, which was determined to be \na consequence of the preterm birth imbalance. The imbalance in preterm births was seen in \nlow- and middle- income countries (RR: 1.57, 95% CI: 1.17, 2.10), but not high- income countries \n(RR: 1.04, 95% CI: 0.68, 1.58). The imbalance was observed from April ─December 2021, but \nnot consistently after December 2021. The reason for the imbalance in preterm births in the trial \nremains unclear. \nTo describe the Pfizer RSVpreF vaccine P hase 3 trial data comparing the trial versus the \napproved dosing interval in more detail, in the full trial with the trial dosing interval, 5.7% of \nbirths were preterm in the vaccinated group compared to 4.7% in the placebo group. When \ndosing is limited to the approved interval, 4.2% of births in the vaccine arm compared to 3.7% in \nthe placebo arm were preterm, showing that the rate of preterm birth decreased as there was \nless opportunity to be born preterm . Also, the imbalance between the vaccine and placebo \ngroups narrowed with the approved dosing interval. In terms of low birth weight (≤2500 grams ) \nand neonatal jaundice, low birthweight and neonatal jaundice were both more common in the \nfull trial population in the vaccinated group compared to placebo group. However, the \nconfidence intervals between tho se 2 groups overlapped and the differences were not \nsignificant. When limited to the approved dosing interval, 4.1% of infants in the vaccine arm had \nlow birth weight compared to 3.4% in the placebo group. Neonatal jaundice was slightly less \n20 https://www.fda.gov/media/165621/download \n20 \n \n    \n \n \n     \n   \n   \n     \n  \n   \n    \n   \n    \n \n  \n   \n  \n \n \n \n    \n \n \n \n \n  \n \n    common among the vaccinated group compared to the placebo, but the confidence intervals overlapped. \nDuring the June ACIP meeting, ACIP members requested additional data regarding the Pfizer \nmaternal RSV vaccine, including the rate of preterm birth by calendar month of birth, birth by \nweek of gestational age, percent of births that were preterm by country, and adverse pregnan cy \noutcomes. Enrollment in the Pfizer Phase 3 trial started in June 2020. The earliest births in the \ntrial were inevitably preterm , so the rate was high in both the vaccine and placebo groups. For \nPfizer, the imbalance was more prominent during August ─Dece mber  2021 and then again in \nApril─May of 2022.\n21 As a reminder, the GSK imbalance was present in April ─December 2021. \nLooking at preterm birth rates by calendar time in the approved dosing interval, preterm birth was less common overall and the temporal patterns were less clear. \nAdditionally, ACIP requested a histogram on the number of births by week of gestational age \nfrom the full Phase 3 trial with the trial dosing interval (24–36 weeks gestation), shown here with \nthe vaccine arm in blue and the placebo arm in gray : \nThe next histogram shows preterm births only (<37 weeks gestation), which illustrates that the \nimbalance in preterm birth begins at 33 weeks gestation: \n21 Data source: Pfizer response to ACIP, unpublished data, July 2023 \n21 \n \n  \n   \n   \n \n \n \n \n  \n \n     \n    \n   \n    \n \n  \n    \n      \n \n  \n    \n   \n    \n \n \n     \n    \n    \n     \n    \n   \n \n   \n  \n \n     \n    \n   \n \n     \n   Looking at a histogram of births by gestational age limited to participants who received doses \nduring the approved interval (32– 36 weeks gestation) , the imbalance is less prominent and is \nonly clearly present at 36 weeks : \nThe ACIP also requested the percent of preterm births by country in the Phase 3 trial. \nImportantly, the US data was the single largest country contributing to the trial and accounted \nfor just under half of all trial participants. In the full trial dosing interval of 24 ─36 weeks in the \nUS, 5.7% of births in the vaccine arm were pre- term compared to 5.3% in the placebo arm. \nHowever, in the approved dosing interval in the US, the direction of this imbalance reversed with \n4% of births in the vaccine arm being preterm compared to 4.4% in the placebo arm. \nThe ACIP also requested data on adverse pregnancy outcomes. Looking at select pregnancy -\nrelated SAEs occurring at any time after vaccination up to 6 months after delivery for the full \nPhase 3 trial population,22 maternal SAEs occurred in 16.2% of the vaccine arm compared to \n15.2% of the placebo arm , with overlapping confidence intervals. FDA is requiring post -\nmarketing studies to assess hypertensive disorders of pregnancy, including pre -eclampsia. In \nthe full trial population, pre-eclampsia occurred in 1.8% of the vaccine recipients versus 1.4% of \nthe placebo recipients. Gestational hypertension occurred in 1.1% of vaccine recipients and 1% \nof placebo recipients. Hypertension occurred in 0.4% of vaccine recipients and 0.2% of placebo \nrecipients. \nAnother consideration of interest is inflammatory neurologic events.23 The Pfizer maternal RSV \nvaccine is the same formulation and dose approved for use in adults ≥60 years of age . Within \nthe trials for this product, a potential safety signal of inflammatory neurologic events was \nidentified among adults ≥60 years of age. A total of 3 cases of interest were recorded among \n20,255 investigational vaccine recipients ≥60 years of age and no cases were observed among \nplacebo recipients. The details of these cases were discussed during the June ACIP meeting \nduring the session on RSV vaccines in older adults. As a reminder, these cases included 1 case \nof Guillain -Barré Syndrome (GBS), 1 case of Miller Fisher syndrome (MFS; a GBS variant ), and \n1 case of undifferentiated motor -sensory axonal polyneuropathy with worsening of pre- existing \n22 Table 3 ABRYSVO package insert Package Insert -ABRYSVO (STN 125768) (fda.gov); Includes all SAEs from vaccination to 6 \nmonths post -delivery (up to approximately 10 months, depending on the gestational age at the time of vaccination). In the phase \n3 RCT, eclampsia occurred in 5 participants (3 in the RSVpreF group and 2 in the placebo group) and HELLP syndrome occurred \nin 5 participants (2 in the RSVpreF group and 3 in the placebo group). \n23 Melgar et al. Use of Respiratory Syncytial Virus Vaccines in Older Adults: Recommendations of the Advisory Committee on \nImmunization Practices — United States, 2023 | MMWR (cdc.gov) \n22 \n \n   \n    \n   \n    \n \n        \n       \n   \n      \n   \n  \n       \n     \n    \n \n \n     \n     \n    \n   \n  \n  \n      \n   \n \n \n    \n    \n \n      \n \n   \n     \n    \n        \n     \n    \n    \n  \n \n  \n      \n     \n  \n  \n   \n   symptoms. No GBS or other demyelinating events were reported in the Phase 2 or 3 trials \namong pregnant people.24 The background rate GBS syndrome in pregnant people is much \nlower than that among older adults.25 In the VSD during 2004─2015, there were 2 cases of G BS \nin pregnant people with an incidence rate of 2.8 per million person years.26 \nIn summary of the Benefits and Harms domain, the WG felt that this is an efficacious vaccine \nthat can prevent RSV LRTI in young infants. However, there was no consensus among the WG \nregarding the clinical importance of the preterm birth imbalance observed in the clinical trials. \nWG members found several points concerning preterm birth. Although not statistically \nsignificant, an imbalance in preterm births was seen in the full trial population. The trial was \npowered for efficacy outcomes and was not designed or powered to detect a 20% increase in \npreterm birth. There may have been less precise dating of gestational age in some sites and \ncountries in the trial, but there is no reason that this should bias towards a preterm birth \nimbalance among vaccinated compared to placebo recipients. The pre -term birth signal in the \nGSK maternal RSV vaccine trial, which also is a stabilized prefusion F- protein vaccine, added to \nthe WG’s concern. \nWG members also found several aspects of the data to be reassuring regarding the preterm \nbirth imbalance. When using the full trial dosing interval, most preterm births (60%) were more \nthan 30 days after vaccination. T here is no known biologic mechanism for vaccines to cause \npreterm birth, particularly more than 30 days after vaccination. When assessed among those \nvaccinated during the approved dosing interval of 32─ 36 weeks, data on preterm birth were \nreassuring to the WG. Specifically, the imbalance in preterm birth was still present but lessened. \nMost infants born preterm in the vaccine group were born at 36 weeks. In the US, which was the \nsingle largest contributing country in the trial, the imbalance in preterm births reversed from the \ntrial dosing interval (trial dosing interval: 5.7% in vaccine vs. 5.3% in placebo recipients ; \napproved dosing interval: 4.0% in vaccine vs. 4.4% in placebo recipients ). Overall, the majority \nof the WG members felt that the approved dosing interval of 32─ 36 weeks gestation could \nreduce the potential risk of preterm birth and the potential for complications from preterm birth, \nboth by preventing preterm birth and because babies born late preterm are less likely to have \ncomplications from preterm birth. This was their major safety concern. \nWhen asked how substantial the desirable anticipated effects are of the Pfizer maternal RSV \nvaccine for the critical and important outcomes, the WG was split between “Large” and \n“Moderate, ” with a narrow majority choosing “Large. ” When asked how substantial the \nundesirable effects are of the Pfizer maternal RSV RSVpreF vaccine for the critical and \nimportant outcomes, the WG responded that they were “S mall. ” When asked about the balance \nof desirable and undesirable effects, the WG determined that the balance favored the \nintervention of the Pfizer maternal RSVpreF vaccine. \n24 https://www.fda.gov/media/168185/download \n25 Myers TR, McCarthy NL, Panagiotakopoulos L, Omer SB. Estimation of the Incidence of Guillain- Barré Syndrome During \nPregnancy in the United States. Open Forum Infect Dis. 2019 Mar 15;6(3):ofz071. doi: 10.1093/ofid/ofz071; and Sejvar JJ, \nBaughman AL, Wise M, Morgan O. Population Incidence of Guillain- Barré Syndrome: A Systematic Review and Meta- Analysis. \nNeuroepidemiology 2011;36:123– 133 \n26 Myers TR, McCarthy NL, Panagiotakopoulos L, Omer SB. Estimation of the Incidence of Guillain- Barré Syndrome During \nPregnancy in the United States. Open Forum Infect Dis. 2019 Mar 15;6(3):ofz071. doi: 10.1093/ofid/ofz071 \n23 \n \n      \n    \n   \n    \n  \n    \n    \n     \n   \n   \n \n      \n    \n \n      \n      \n      \n   \n \n \n    \n   \n   \n   \n   \n     \n    \n  \n \n     \n    \n    \n     \n   \n      \n   \n  \n  \n \n    \n     \n   \n          \n   \n    \n     \n   Moving to the Values domain, the results of a values survey of pregnant and recently pregnant \npeople conducted during December 2022─ January 2023 conducted by the University of Iowa, \nRAND, and the CDC were presented during the June ACIP meeting. Among the respondents, \n68% had knowledge of RSV prior to taking the survey and 61% of respondents said they \n“definitely ” or “probably ” would get an RSV vaccine while pregnant. Among those who did not \nrespond that they “definitel y” would get an RSV vaccine while pregnant, safety concerns, lack of \nRSV knowledge, and concerns about vaccination causing or intensifying RSV infection were the \ntop reasons for not wanting an RSV vaccine during pregnancy.27 It also is important to look at \nthe uptake of other vaccines in pregnancy. In the US, coverage for recommended vaccines \namong pregnant people decreased during the pandemic and varies by race and ethnicity.28 \nTDAP vaccination coverage was 53.5% in the 2020─2021 season and 45.8% in the 2021─2022 season. Rates of TDAP coverage were higher in White, non-Hispanic women than among \nBlack, non-Hispanic  women during the 2020─2021 and 2021─2022 seasons. \nWhen asked whether the WG felt that pregnant people feel the desirable effects are large \nrelative to the undesirable effects , the answered “probably yes. ” When asked if there is \nimportant uncertainty about , or variability in, how much pregnant people value the main \noutcomes , the WG was evenly split between “ probably important uncertainty or variability ” and \n“probably not important uncertainty or variability. ” \nThere were limited data to inform the Acceptability domain and no updates since the June ACIP \nmeeting. A study in England\n29 assessed support of an RSV vaccine among maternity health \ncare professionals (HCP) , specifically obstetricians and midwives . If the vaccine was routinely \nrecommended , 47% of responders said they “ definitely ” would recommend the vaccine, 34% \n“likely ” would support a routinely recommended RSV vacci ne, 14% were “not sure,” 4% said \n“unlikely,” and 0.5% said “very unlikely .” When asked i f RSV prevention with the Pfizer maternal \nRSV vaccine was acceptable to key stakeholders, the majority of the WG answered “yes” and a \nminority answer ed “probably yes. ” \nIn terms of the F easibility domain, the storage and handling requirements, the vaccine is \nsupplied as single 0.5 mL dose or as a 5- pack or 10- pack of single- dose kits . Reconstitution is \nrequired, with  a single dose vial of lyophilized powder and reconstitution supplies included in the \nkits. The p roduct should be refrigerated (2° –8°C) in the original container and protected from \nlight. After reconstitution, the product should be administered within 4 hour s and otherwise \ndiscarded.30 Additionally, most pregnant patients receive Tdap vaccine in an obstetrician’ s or \nmidwife ’s office. Therefore, it is likely that pregnant patients also most often would receive RSV \nvaccine at their prenatal care provider ’s offi ce.31 \n27 CDC and University of Iowa/RAND survey, unpublished \n28 Flu, Tdap, and COVID -19 Vaccination Coverage Among Pregnant Women – United States, April 2022 | FluVaxView | Seasonal \nInfluenza (Flu) | CDC; https://www.cdc.gov/flu/fluva xview/pregnant -women- apr2022.htm \n29 Wilcox CR, Calvert A, Metz J, et al. Attitudes of Pregnant Women and Healthcare Professionals Toward Clinical Trials and \nRoutine Implementation of Antenatal Vaccination Against Respiratory Syncytial Virus: A Multicenter Questionnaire Study. The \nPediatric Infectious Disease Journal. 2019 Sept;38(9):944- 951. DOI: 10.1097/INF.0000000000002384. \n30 Package Insert -ABRY SVO (STN 125769/26) (fda.gov) \n31 https://www.cdc.gov/flu/fluvaxview/pregnant -women- apr2022.htm \n24 \n \n    \n     \n    \n   \n   \n   \n      \n  \n     \n \n   \n  \n \n    \n  \n    \n   \n     \n   \n   \n   \n \n  \n    \n    \n     \n  \n    \n    \n  \n  \n    \n   \n    \n   \n \n \n     \n    \n  \n \n      \n   \n \n   \n  Another important consideration for feasibility is simultaneous administration of RSV vaccine \nwith other vaccines in pregnant people. Pregnant people potentially may be eligible to receive \nRSV, T dap, COVID -19, and influenza vaccines during the same visit. There are limited data \nregarding simultaneous administration, but there was a Pfizer study32 in healthy non- pregnant \nwomen 18─49 years of age on simultaneous administration of Tdap and Pfizer RSV vaccine \nthat found decreased immune response to pertussis components, meaning that the non-\ninferiority criteria were not met. However, given the lack of correlates of protection for pertussis, \nit is unclear how this might impact protection against pertussis from maternal Tdap when \nsimultaneously administered with RSV vaccine. Tdap is recommended every pregnancy, \npreferably during the early part of gestational weeks 27─ 36,33 which means that Tdap preferably \nwould be given before 32 weeks and RSV vaccine would be given at or after 32 weeks. \nHowever, in MarketScan data from 2018─2021,34 about half of captured Tdap doses were given \nbefore 32 weeks gestation. \nAnother important consideration is that RSV vaccine is 1 of 2 available preventive products for \nRSV in infants. Either RSV vaccination during pregnancy or nirsevimab administration for the \ninfant after birth can be used to prevent RSV disease in infants. The WG felt strongly that both \nproducts are not needed for most infants. The pregnant person and their prenatal care provider \nwill need to make the decision during pregnancy regarding which RSV prevention product to \nuse. Many prenatal care providers may not have time to discuss options for RSV prevention \nwith their patients. In addition, prena tal care providers may not feel equipped to discuss \nnirsevimab since this product will be given to the infant after birth. \nRegarding the timing of RSV vaccine dosing during the calendar year, RSV vaccine dosing \ncould be implemented for pregnant people as a seasonal campaign or year-round.  The WG \nunanimously supported the use of a seasonal dosing strategy for maternal RSV vaccine \nbecause this would maximize cost -effectiveness , maximize the benefits for infants, and target \nRSV vaccine dosing to inf ants who will be in the first months of life during the RSV season. \nImportantly, nirsevimab is available for infants who are born out of season for whom maternal \nvaccine protection would have waned by RSV season. The WG supported seasonal dosing \nbeginning in September and going through January in most of the continental US based on \ntypical pre -pandemic seasonality. This aligns with implementation of influenza vaccine and \nwould simplify implementation for prenatal care providers. The WG felt that jurisdictions in which \nRSV seasonality differs from most of the continental US should have flexibility regarding start and stop of administration of RSV vaccine in pregnant people. These jurisdictions include \nAlaska and jurisdictions with tropical climates (e.g., parts of Florida, Puerto Rico, US Virgin \nIslands, Hawaii, Guam, and US -affiliated Pacific Islands ). \nWhen asked whether the Pfizer maternal RSV vaccine is feasible to implement , the majority of \nthe WG answered “yes” and a substantial minority answered “probably yes. ” \n32 Peterson et al. Safety and Immunogenicity of a Respiratory Syncytial Virus Prefusion F Vaccine When CoadministeredWith a \nTetanus, Diphtheria, and Acellular Pertussis Vaccine.The Journal of Infectious Diseases. 2022 June 15; 225(12): 2077– 2086. doi: \n10.1093/infdis/jiab505 \n33 CDC, https://www.cdc.gov/vaccines/vpd/dtap- tdap- td/hcp/recommendations.html \n34 MarketScan data, 2018- 2021 \n25 \n \n     \n   \n   \n     \n    \n    \n   \n \n    \n     \n    \n \n    \n \n     \n    \n     \n    \n \n   \n     \n    \n     \n      \n    \n      \n     \n \n  \n  \n    \n   \n      \n    \n   \n   \n    \n   \n   \n   \n \n \n  \n \n    \n    \n \n  \n   \n   \n   Regarding the R esource Use Domain, the ACIP heard presentations earlier from D rs. Hutton \nand Ortega -Sanchez on economic analyses. Dr. Hutton showed scenarios for cost -effectiveness \nby months of RSV vaccine dosing during the calendar year. The base case was about $400,000 \nper QALY. If the months of dosing were limited to target dosing to pregnant people whose \ninfants would be in the first months of life during the RSV season, the ICER decreased and the \ncost- effectiveness improved. Importantl y, the ICER would be $167,000 per QALY is dosing is \nprovided during the September ─January timeframe. The WG interpretation was that while RSV \nvaccine may improve outcomes, it also would increase costs. The base case model showed an \nicer of about $400,000 p er QALY and assumed year -round dosing of this vaccine and typical \nRSV seasonality in most of the continental US. The WG felt that this vaccine would not be cost -\neffective under the base case conditions. However, cost -effectiveness would be improved by \nusing a seasonal dosing strategy during September ─January in most of the continental US. \nThus, the WG unanimously supported the use of a seasonal dosing strategy. \nWhen asked whether Pfizer maternal vaccine use would be a reasonable and efficient allocation \nof resources , a substantial majority of the WG answered “ probably yes ” and a substantial \nminority answered “yes.” It is important to note that the WG responses were based on seasonal \ndosing for RSV vaccine specifically during September ─January in most of the continental US. \nData for the final domain of Equity have been presented before. National studies of death \ncertificates found higher rates of RSV -associated deaths among non- Hispanic Black children \ncompared with non -Hispanic White infants in children 1-4 years of age.35 ICU admission rates \nfor RSV among non- Hispanic Black infants <6 months of age were 1.2 to 1.6 times higher than \namong non -Hispanic White infants.36 In one study, RSV hospitalization rates were 4 to 10 times \nhigher among Alaska Native and American Indian (AI/AN) children <24 months than the rate in \nthe general population.37 However, it is important to note that the study was limited to specific \npopulations and might not be broadly representative of risk in all A I/AN children. \nRegarding Medicaid coverage for pregnant people and vaccines during pregnancy , by federal \nlaw, all states provide Medicaid coverage for pregnancy -related services to pregnant women \nwith income levels up to 138% of the federal poverty level.38 In 2021, 41% of mothers had \nMedicaid at the time of birth,39 making Medicaid the largest payer for maternity care in the US. If \nrecommended, ACIP would vote on a Vaccines for Children (VFC) resolution for the vaccine for \npregnant people < 19 years of age. B eginning on October 1, 2023, when the Inflation Reduction \nAct of 2022 (IRA) provisions become effective, state Medicaid agencies will be required to \nrecover vaccines and their administration without cost -sharing for nearly all adult beneficiaries \ncovered under traditional Medicaid, if the CDC recommendations apply. Regarding other \ninsurance coverage, meaning commercial insurance for vaccines during pregnancy under the Affordable Care Act (ACA) and its implementing regulations, ACIP recommendations that have \nbeen adopted by CDC and are listed on CDC’s I mmunization Schedules generally are required \nto be covered by group health plans and health insurance issuers without any cost -sharing \nrequirements. \n35 Hansen et al. The Use of Death Certificate Data to Characterize Mortality Associated With Respiratory Syncytial Virus, \nUnspecified Bronchiolitis, and Influenza in the United States, 1999- 2018 J Infect Dis. 2022 Aug 15;226(Supplement 2): S255– \nS266. \n36 Unpublished data from RSV -NET, CDC. \n37 Atwell et al. RSV Among American Indian and Alaska Native Children: 2019 to 2020 Pediatrics. 2023 Aug 1;152(2):e2022060435 \n38 https://www.kff.org/womens -health- policy/issue -brief/medicaid- coverage- for-women/ \n39 https://www.medicaid.gov/sites/default/files/2023- 04/beneficiary -profile -2023.pdf \n26 \n \n     \n  \n        \n \n \n  \n     \n   \n      \n     \n     \n    \n  \n    \n   \n     \n   \n   \n  \n  \n \n      \n    \n   \n   \n   \n    \n   \n     \n     \n     \n    \n \n \n      \n    \n    \n     \n      \n        \n \n   \n \n  \n    \n     \n     \n   \n   \n  \n     When asked what the impact of the Pfizer maternal RSV vaccine on health equity would be , the \nWG’s answers ranged and there was no clear majority . The most common answer among the \nWG was “probably increased, ” the second most common was “probably no impact, ” and the \nthird most common was “increased. ” \nIn summar y, regarding the use of the Pfizer maternal RSV vaccine to prevent RSV in infants , \nthe WG judged this is an important public health problem, the desirable anticipated effects are \nlarge, the undesirable anticipated effects are small, the balance of desirable and undesirable \neffects favor the intervention, and that the target population probably feels the desirable effects \nare large relative to the undesirable effects. Half of the WG chose that there is probably \nimportant uncertainty or variability in how patients value the outcome, and half chose there is \nprobably not important uncertainty or variability. The WG judged that the intervention is \nacceptable to key stakeholders , is feasible to implement, and is probably a reasonable and \nefficient allocation of resources with seasonal dosing. The WG had varied answers as to \nwhether the intervention would increase health equity, ranging from probably no impact to increased health equity. The majority of the WG felt that the desirable consequences probably \noutweigh the undesirable consequences in most settings, and a substantial minority felt that the \ndesirable consequences clearly outweigh the undesirable consequences in most settings. The \nmajority opinion was in favor of recommending the Pfizer maternal RSV vaccine, and there was \na minority opinion to recommend the intervention based on shared clinical decision- making. \nTo summarize the WG’s considerations overall, for benefits and harms, the majority of the WG \nwas supportive of the intervention with the Pfizer maternal RSV vaccine for pregnant people \nwith the approved dosing interval of 32─ 36 weeks gestation. They found the data on preterm \nbirths, when assessed among those vaccinated during the approved interval, to be reassuring. \nThey felt the approved dosing interval of 32─ 36 weeks gestation would reduce the potential risk \nof preterm birth and the potential for complications from preterm birth, which was their major \nsafety concern. All WG members endorsed the importance of post -introduction vaccine safety \nmonitoring. The WG unanimously supported the use of a seasonal dosing strategy, which would \nmaximize benefits and cost -effectiveness. The WG supported that RSV vaccine dosing should \noccur during September ─January in most of the continental US and felt that jurisdictions in \nwhich RSV seasonality differs from most of the continental US should have flexibility regarding \nstart and stop of administration of RSV vaccine in pregnant people. \nThe WG also considered the implications of RSV vaccine being 1 of 2 available preventive \nproducts for RSV in infants. The WG expressed that pregnant people should have options for \nRSV prevention, given that nirsevimab may not be readily available in all settings. In addition, \npregnant people and their providers may have preferences regarding these 2 products. The WG \nalso stated that pregnant people should be made aware that they either could receive RSV \nvaccine during pregnancy or that nirsevimab could be given to the infant, but that most infants \nwould not need both. The WG expressed that pregnant people should be informed regarding \nthe risks and benefits of both products before making a decision. \nThe WG had extensive discussions regarding a full recommendation versus a shared clinical \ndecision- making recommendation. Most WG members support a full recommendation. They felt \nthe approved dosing interval would reduce the potential risk of , and complications from , preterm \nbirth. They stress ed the importance of clear vaccine recommendations and noted that providers \nwho will help pregnant people decide which product to receive generally have less familiarity \nwith the data than ACIP does. They expressed that shared clinical decision- making \nrecommendations can be confusing, hard to implement for providers , can lead to lower vaccine \nconfidence and uptake of vaccine, and potentially could influence support for the vaccine in \n27 \n \n     \n   \n  \n \n   \n \n     \n  \n   \n    \n  \n      \n   \n \n   \n \n   \n \n \n  \n \n \n \n \n \n    \n    \n   \n     \n  \n  \n       \n  \n  \n    \n    \n \n \n \n        \n  \n   \n    \n   \n    \n    \n   \n \n  lower -and middle- income countries where nirsevimab may not be available. A minority of WG \nmembers supported a recommendation with shared clinical decision- making. They noted that \nwithout shared clinical decision- making, a full recommendation could result in some providers \nrecommending RSV vaccine during pregnancy without discussing with pregnant patients that \nnirsevimab is an option. They cited the potential risk for preterm birth and neuroinflammatory \nevents and cited that the same vaccine is recommended under shared clinical decision- making \nfor adults ≥60 years and older. It is important to note that ACIP generally makes shared clinical \ndecision- making recommendations when individuals may benefit from vaccination, but broad \nvaccination of people in that group is unlikely to have population- level impacts. As discussed \nduring the June ACIP meeting, the WG noted that currently there are no data available on the \nefficacy of the first lifetime dose during subsequent pregnancies, or the safety of additional \ndoses given in subsequent pregnancies. The WG felt that it was too early to decide whether \nadditional doses should be given in subsequent pregnancies due to the lack of data, that \nadditional data are needed to inform whether additional doses in subsequent pregnancies would \nbe indicated, and that recommendations can be updated in the future. \nWith all of th is in mind, the proposed voting language put forward for a potential vote during this \nmeeting was as follows: \n“Maternal RSV vaccine is recommended for pregnant people during 32 through 36 weeks \ngestation, using seasonal administration, to prevent RSV lower respiratory tract infection in \ninfants.” \nUpdated Clinical Considerations for Use of Both Nirsevimab and Pfizer RSVpreF Vaccine \nJefferson Jones MD, MPH, FAAP, CDR USPHS (CDC/NCIRD) discussed the updated clinical \nconsiderations for the use of maternal RSVpreF vaccine and nirsevimab. Beginning with the \nproposed clinical considerations for use of the maternal RSV vaccine, as Dr. Fleming -Dutra \nreviewed, the WG discussion points that shaped these considerations included that as \nproposed, the maternal RSV vaccine would be recommended for pregnant people during 32─ 36 \nweeks gestation with seasonal administration or during September ─January in most of the \ncontinental US in jurisdictions with seasonality that differs from most of the continental states, \nincluding Alaska and jurisdictions with tropical climates (e.g., parts of Florida, Hawaii, Puerto \nRico, Guam, US Virgin Islands, and the US- affiliated Pacific Islands ). In those jurisdictions, \nproviders would follow state, local, or territorial guidance on the timing of administration. The \nmaternal RSVpreF vaccine may be administered simultaneously with other eligible \nvaccinations.40 \nBefore reviewing the clinical considerations for use of both the maternal RSV vaccine and \nnirsevimab, Dr. Jones summarize d the considerations of the WG. He first discussed 2 groups of \ninfants born to vaccinated mothers who were previously considered for nirsevimab during the \nJune ACIP meeti ng, preterm infants and infants born outside of the RSV season. As proposed \nregarding infants born prematurely, the maternal RSV vaccine recommendation is for \nadministration beginning at 32 weeks gestation. F rom the time of maternal vaccination, 14 or \nmore days are likely needed for development and transplacental transfer of maternal antibodies \nto protect the infant and nirsevimab is recommended for infants born within 14 days of \nvaccination. The earliest an infant can be born and hav e maternal vaccine- induced protection is \n40 https://www.cdc.gov/vaccines/hcp/acip -recs/general -recs/index.html \n28 \n \n  \n  \n \n   \n      \n    \n     \n  \n  \n   \n  \n \n \n  \n   \n   \n   \n   \n   \n       \n   \n   \n    \n \n    \n     \n  \n    \n   \n \n   \n     \n   \n \n \n    \n \n \n    \n     \n \n   \n   \n    \n \n \n   \n   \n   \n   34 weeks gestation. This means that all infants born at <34 weeks gestation will be \nrecommended to receive nirsevimab.41 \nRegarding infants born outside of the RSV season, protection from maternal vaccination may \nbegin to wane after 3 or more months. For example, this has been seen with the influenza and \nCOVID -19 vaccines .42 WG members initially were concerned that some infants born outside of \nthe RSV season and born to vaccinated mothers may benefit from nirsevimab in order to boost protection when entering the RSV season. However, because maternal RSV vaccine \nadministration is now proposed to be recommended during September ─January, most infants of \nvaccinated mothers will be born during the RSV during October ─March . Mothers of infants born \noutside of the RSV season during April ─September will not have been vaccinated, and \nnirsevimab will be recommended for these infants. \nOther WG considerations regarding the use of both maternal RSV vaccine and nirsevimab \nincluded that there are 2 products available to protect infants from RSV LRTI . For infants born to \nvaccinated mothers , the addition of nirsevimab may provide incremental protection, but there \nare no efficacy data on the use of nirsevimab in infants born to vaccinated mothers, so this is \nunknown. There also are no safety data on the use of nirsevimab in infants born to vaccinated \nmothers , but nirsevimab trials included infants with maternal infection- induced antibodies and \nthe risk is likely minimal. The WG felt that for most infants, administering both products is not \nneeded and would not be a reasonable and efficient allocation of resources based on the cost -\neffectiveness analysis presented earlier in the day. Of note, documentation of maternal \nvaccination status may not be available to the infant ’s HCP. \nMost WG members felt that pregnant people should be aware that both maternal vaccination \nand nirsevimab are options when deciding whether to be vaccinated. However, HCP of \npregnant people may not have the time or feel equipped to discuss nirsevimab when \ncounseling. The WG felt that in rare situations, flexibility is needed for providers to be able to \nadminister nirsevimab when it is clinically warranted for infants born to vaccinated mothers. \nExamples include conditions in pregnant people resulting in an inadequate immune response to \nvaccine or decrease in transplacental antibody transfer.\n43 Also, infants who have undergone \ncardiopulmonary bypass leading to a loss of maternal antibodies44 and infants with su fficiently \nincreased risk for severe disease to warrant nirsevimab because of the potential increased benefit. \nThe following are the proposed clinical considerations for the use of the maternal RSV vaccine \nand nirsevimab : \nEither maternal vaccination or use of nirsevimab in the infant is recommended to prevent \nRSV LRTI , but administration of both products is not needed for most infants. \nHealth care providers of pregnant people should provide information on both products and \nconsider patient preferences when determining whether to vaccinate the pregnant patient or \nto not vaccinate and rely on administration of nirsevimab to the infant after birth. \n41 https://www.cdc.gov/vaccines/pregnancy/vacc- during- after.html \n42 Kampmann NEJM 2023; Nunes F1000Res 2018;and Zerbo Nat Commun 2023. \n43 Palmerira Clin Dev Immunol 2012 \n44 Feltes J Pediatr 2003 \n29 \n \n   \n \n  \n \n \n \n   \n      \n   \n    \n   \n     \n       \n   \n \n  \n \n    \n   \n     \n  \n  \n     \n     \n  \n \n     \n   \n    \n      \n    \n    \n  \n      \n \n   \n   It is important to note that both products are safe and effective in preventing RSV LRTIs in \ninfants. The following displays potential information that could be shared with patients on the \nrelative risks and benefits of a maternal RSV vaccine and nirsevimab: \nRelative benefits of maternal vaccination include that a maternal vaccine provides protection \nimmediately after birth, when infants are at the highest risk for severe RSV disease. A maternal \nvaccine may be more resistant to virus mutation compared w ith monoclonal antibodies, \nalthough RSV does not mutate rapidly. While both products require an injection, use of a \nmaternal vaccine avoids injection of the infant. Relative risks of maternal RSV vaccination \ninclude that maternal vaccine- induced protection is reduced if fewer vaccine- induced antibodies \nare produced or are transferred from the mother to the baby (e.g., mother immunocompromised \nor the infant is born soon after vaccination. There is a potential risk of preterm birth , but \nadministration at 32─ 36 weeks reduces this risk. \nThe relative benefits of nirsevimab include studies of antibody levels suggest ing that protection \nfrom nirsevimab might wane more slowly. Administration of nirsevimab can provide antibodies directly if an infant receives less antibodies from the mother. Since nirsevimab is provided after \nbirth, there are no risk of adverse pregnancy outcomes. Relative risks of nirsevimab include that \nthere may be potential limited availability of nirsevimab during the 2023─2024 RSV season. In \nthe setting of a maternal vaccine, nirsevimab would be recommended for infants <8 months of \nage born during or entering their first RSV season if the mother did not receive the RSV vaccine \nor it is unknown if the mother received an RSV vaccine or mother was vaccinated, but the infant \nwas born <14 days after vaccination. Nirsevimab is not needed for most infants born ≥14 days \nafter maternal vaccination. \nNirsevimab can be considered in circumstances when the mother has received RSV vaccine \n≥14 days prior to birth . Nirsevimab can be considered in rare circumstances, per the c linical \njudgment of the HCP , the potential incremental benefit of administration is warranted. One \nexample is infants born to pregnant people who may not mount an adequate immune response \nto vaccination (e.g., people with immunocompromising conditions ) or have conditions \nassociated with reduced transplacental antibody transfer (e.g., people living with HIV \ninfection).\n45 Other examples include infants who have gone undergone cardiopulmonary \nbypass, leading to a loss of maternal antibodies46 or infants with substantial increased risk for \n45 Palmerira Clin Dev Immunol 2012 \n46 Feltes J Pediatr 2003 \n30 \n \n     \n  \n   \n \n     \n     \n \n \n \n  \n \n \n \n   \n  \n  \n  severe RSV disease (e.g., hemodynamically significant congenital heart disease or ICU \nadmission requiring oxygen at discharge ). Recommendations for nirsevimab can be \nsummarized in the following algorithm . \nNirsevimab is recommended to all infants aged <8 months on the day of administration who \nmeet all 3 of the following criteria : \nDetails on timing, including special situations and flexibility, are described in the footnotes: \nThese were previously presented during the August ACIP meeting under nirsevimab and \ndescribed in the published nirsevimab recommendation in the Morbidity and Mortality Weekly \nReport (MMWR ). \n31 \n \n   \n \n     \n \n \n \n \n \n \n \n  \n \n \n\n\n\n\n\n\n \n \n \n \n \n \n  \n \n  \n \n    \n          \n    \n \n   \n  \n \n \n     \n       \n     \n    \n   \n \n \n  \n      \n     \n  \n   \n \n  \n      \n   \n   \n  \n  \n \n   \n  \n   \n   \n   Implementation Considerations for Maternal RSV Vaccine \nGeorgina Peacock, MD, MPH (CDC/NCIRD) presented m aternal RSV vaccine implementation \nConsiderations , including the following: \nVaccine storage, handling, and administration \nCost of vaccine \nInsurance coverage \nSupply and availability \nComplexity of immunization schedule \nVaccine demand and coverage in pregnant people Obstetric and pediatric provider roles in vaccination decisions \nImmunization information systems \nCommunication challenges \nFor Pfizer RSV vaccine storage, handling, and administration, the overall clinical implementation \nis similar to other vaccines. It is stored at 2◦ to 8◦ C and administered as a single dose through \nan intramuscular ( IM) route. Additional steps are required for dilution, including reconstitution of \nthe lyophilized antigen component with the sterile water diluent component.\n47 The proposed \nrecommendations to ACIP allow for simultaneous administration with other recommended \nvaccines,  and there is som e consideration that increasing the number of vaccines could lead to \nlimited storage space. \nThere has been a lot of conversation already about cost of the vaccine at $295 a dose for the \nPfizer RSV compared to Tdap that is approximately $46 to $52.48 This cost is lower than the \ninfant nirsevimab cost of $495 for the private sector cost. Reimbursement and cost recovery \nchallenges already have been identified by providers and practices as implementation barrier s \nfor maternal immunization. Among providers, f inancial concerns are a leading barrier to \nmaternal immunization.49 \nRelated to insurance coverage, most pregnant people are covered by some form of private \npayer or Medicaid. About 52% of pregnant people have private insurance, 41% have Medicaid, \nand about 4% are likely uninsured and are considered “ self-pay.”50 If recommended, ACIP \nwould vote on a V FC resolution for maternal RSV vaccine in people aged <19 years . For people \n≥19 years of age, there would be limited availability through the 317 program in jurisdictions. In \nterms of i nsurance coverage for infant nirsevimab , the ACIP already recommended nirsevimab \nas a routine immunization. Therefore, it will be covered under the ACA without cost -sharing by \nthe patient starting in the effective plan year .51 Anecdotally, plans are starting to let people know \nthat they will start covering nirsevimab when it becomes available in the coming weeks. \nNirsevimab is included in the V FC program for eligible children, so about 50% of children in the \nUS will be able to access nirsevimab at no cost. \n47 https://www.fda.gov/media/168889/download?attachment \n48 Current CDC Vaccine Price List | CDC \n49 https://www.sciencedirect.com/science/article/abs/pii/S0749379717306396#f0010 \n50 https://www.cdc.gov/nchs/products/databriefs/db468.htm \n51 https://www.law.cornell.edu/uscode/text/42/300gg- 13 \n32 \n \n    \n    \n   \n    \n    \n    \n   \n \n \n      \n \n \n \n \n   \n  \n    \n   \n    \n        \n  \n \n   \n     \n   \n      \n   \n        \n   \n    \n     \n   \n \n  \n \n     \n   \n  \n  \n   \n   With regard to supply and availability of maternal RSV vaccine and nirsevimab during the 2023– \n2024 RSV season , there are no anticipated supply/demand mismatches . Because the Pfizer \nmaternal RSV vaccine is the same product in use for adults ≥60 years of age, availability is \nexpected shortly after ACIP recommendations. Nirsevimab likely will be available in late \nSeptember or early October . There were some conversations during the last ACIP meeting \nabout delivery in birthing hospitals versus outpatient settings. Efforts are underway to increase \nthe number of birthing hospitals that will administer nirsevimab , particularly under the VFC \nprogram. \nIt is important to point out the increas ing complexity of the maternal immunization schedule as \nillustrated in this figure: \nThe maternal immunization schedule is increasingly complex in terms of d ifferent timing of \nvaccines based on the season and/or gestational age, with seasonal timing varying in some \nlocations. In addition, there is a limited window for RSV vaccine administration. The willingness \nof pregnant people to accept multiple vaccines in pregnancy also is unclear. In a survey of \npregnant people, approximately 12% said they would accept no vaccines and about 49% said \nthey would accept 1 or 2 vaccines .52 Uptake of vaccines among pregnant people has declined \nand disparities persist.53 \nImportant decisions will need to be made regarding w hether to administer maternal RSV \nvaccine or infant nirsevimab. Studies continue to demonstrate that HCPs are pregnant people’s \nmost trust ed source of information on vaccines, and that provider recommendation is a strong \npredictor of vaccination.54 However, one survey show ed that two- thirds of obstetricians did not \nfeel comfortable providing information about routine childhood immunizations or that that was \ntheir role.55 In terms of pediatric provider roles in immunization decisions, recommendations for \nnirsevimab that are contingent upon knowledge of maternal vaccination status could be challenging if the pediatric provider does not receive the maternal record. Verbal report s of \nvaccines received during pregnancy may not be reliable.\n56 Therefore, pediatric providers may \nneed to make decisions on nirsevimab administration without having complete information on maternal vaccination status. \n52 CDC and University of Iowa/RAND survey, unpublished \n53 https://www.cdc.gov/flu/fluvaxview/pregnant -women- apr2022.htm \n54 Lutz C, et al. Understanding barriers and predictors of maternal immunization: Identifying gaps through an exploratory literature \nreview. Vaccine 36 (2018): 7445- 7455 \n55 https://link.springer.com/article/10.1007/s10995-011- 0936-0 \n56 https://www.cdc.gov/mmwr/volumes/66/wr/mm6641a3.htm \n33 \n \n     \n    \n     \n     \n       \n   \n   \n \n    \n      \n \n  \n    \n     \n \n \n      \n   \n     \n     \n   \n   \n     \n \n \n \n     \n    \n \n   \n   \n \n \n \n \n \n  \n   \n      \n \n \n \n  \n   \n  \n \n \n  \n \n \n  \n  \n Moreover, s tate Immunization Information System s (IISs) vary in what they capture related to \nadult immunization. Pregnancy status is not identified in IIS, though potentially RSV vaccine \nadministrations in adult women <age 60 years of age could be used as a proxy for RSV vaccine \nadministration. There is not a way currently to link maternal and infant i mmunization records in \nIISs, so it is not possible through these systems at this point to use that to forecast whether \ninfant nirsevimab immunization is needed. In some state policies, there is not an ability for \npediatric providers to review adult records or records of individuals who are not their patients. \nAs always in immunization implementation, there are some communication challenges. This \nincludes use of t erms like “vaccine” for the maternal product versus “immunization” for the infant \nproduct . Conveying potential risks and benefits of each approach and helping the pregnant \nperson make an informed decision, including the potential but undetermined risk of preterm birth \nwith maternal immunization, is going to take time for providers. D iscussing financial implications \nwith a patient in a setting of uncertainty related to coverage in the first year of implementation \nmay be challenging. \nA lot of work is being done at CDC to address communication activities. There has been \nformative research and message testing, including with focus groups and in- depth interviews to \nhelp inform the ultimate communication activities that will be done for the public. There have \nbeen surveys of parents of young children and also pregnant and recen tly pregnant people. \nWith that information, patient and provider education materials are being developed. There also \nare some partnerships with HCP organizations and organizations that serve pregnant people. \nThere also is an intention to utilize social media across all of CDC’ s platforms. \nVaccines for Childrens Resolution \nJeanne Santoli, MD, MPH (CDC/NCIRD) indicated that the purpose of this resolution was to: 1) \nadd an RSV vaccine for pregnant people aged <19 years to the program ; and 2) update the \nlanguage regarding the recommended vaccine schedule for nirsevimab to take into account \nRSV vaccine for use during pregnancy. The eligible groups include pregnant people aged <19 \nyears. The recommended vaccination schedule and intervals included the language that was \nreviewed during this session: \nDuring 32 through 36 weeks gestation, with seasonal administration. This would be during September through January in most of the continental United States. In jurisdictions with \nseasonality that differs from most of the continental Unites States (e.g., those with tropical \nclimates, Alaska), providers should follow state, local, or territorial guidance on timing of administration. \nEither RSV vaccination during pregnancy at 32 through 36 weeks gestation or nirsevimab administration for infants age <8 months shortly before or during the RSV seasons is \nrecommended to prevent RSV lower respiratory tract infection, but both products are not \nindicated for most infants. \nRecommended DosageRefer to product package inserts. \nContraindications and Precautions \nContraindications can be found in the package inserts available at: \nhttps://www.fda.gov/media/168889/download?attachment \n34 \n \n  \n \n \n \n      \n  \n \n \n    \n \n \n \n   \n   \n  \n \n \n \n \n   \n \n     \n     \n   \n     For t\nhe nirsevimab component, the only change was that now there are 2 components to the \neligible gr oups: \nInfants aged <8 months born during or entering their first RSV season \nChildren aged 8- 19 months as noted in Table 1 who are at increased risk of severe RSV \ndisease and entering their second RSV season \nNo changes were made to the Table 1: \nLanguage was added to Table 2 for the first season stating, “whose mother’s receipt of RSV \nvaccine is unknown or who was born within 14 days of maternal vaccination” and the rest of the resolution is the way it appeared in August 2023 : \nThis recommended vaccination schedule and intervals language also has been added and there \nis some language in each component of the resolution that refers to the other components: \n“For most infants aged infants aged <8 months born during or entering their first RSV season \nwhose mother received an RSV vaccine 14 or more days prior to birth, nirsevimab is not \nneeded. Nirsevimab can be considered in rare circumstances when, per the clinical judgment of \nthe healthcare provider, the potential incremental benefit of administration is warranted. ” \n35 \n \n  \n  \n \n  \n  \n \n \n \n \n    \n \n  \n   \n \n \n \n \n \n     \n       \n    \n   \n  \n    \n  \n    \n  \n       \n    \n     \n   \n \n \n   \n   \n  \n     \n    \n  \n \n    \n  \n   \n    \n     \n     \n   \n     \n    \n   \n The recommended dosage, contraindications and precautions, and standard documents \nstatement about ACIP recommendations or notices within 6 months remained unchanged: \nRecommended Dosage\nRefer to product package inserts. \nContraindications and Precautions \nContraindications and Precautions can be found in the package inserts available at: \nhttps://www.accessdata.fda.gov/spl/data/2f08fa60 -f674-432d- 801b -1f9514bd9b39/2f08fa60-\nf674- 432d -801b- 1f9514bd9b39.xml \n[If an ACIP recommendation or notice regarding RSV prevention is published within 6 months \nfollowing this resolution, the relevant language above (except in the eligible groups sections) will \nbe replaced with the language in the recommendation and incorporated by reference to the publication URL] . \nPfizer Statement \nLuis Jodar, MD (Chief Medical Officer , Vaccines & Antivirals, Pfizer) thanked the ACIP for \nthe opportunity to speak. Pfizer is excited about the recent FDA approval of the maternal \nindication for RSV vaccine, ABRYSVO ™. Last Fall, the US experienced a triple epidemic of \nRSV, influenza, and COVID -19 infections , making national headlines. With the threat of another \ntriple epidemic, having multiple options for RSV prevention for infants will be more important \nthan ever. As shown in the from the data on efficacy in the randomized controlled trial s (RTCs) , \nthe maternal RSV vaccine provides infants with a high degree of protection against RSV immediately from birth when infants are at highest risk for severe disease and maintains this \nprotection for at least 180 days. This is even more important when considering equity. Medicaid recipients miss or cancel a substantial proportion of their well -child visits in the first 6 months of \nlife, with only 25% attending all recommended well -child visits. In contrast, more than 90% of \nMedicaid mothers attend at least 1 visit prior to delivery . With an estimated 41% of pregnant \nindividuals on Medicaid, maternal immunization provides a secure, stable, and equitable \napproach to RSV prevention for newborns. \nRegarding the concern raised about an imbalance in pre -term birth s, the totality of the data \nsupports a favorable benefit -risk profile for maternal vaccination as supported by the external \nData Monitoring Committee ( DMC ), the FDA’s Vaccines and Related Biological Products \nAdvisory Committee (VRBPAC), and FDA licensure. The US indication of 32─36 weeks is \nreassuring about the potential risk of preterm birth. Pfizer has committed to 4 post-licensure \npharmacovigilance studies. The safety surveillance systems in place through Pfizer’s post -\nmarketing commitments, a long with the CDC and FDA systems presented during this meeting, \nare sensitive, timely, powerful , and can detect any safety signals should any arise. Pfizer want s \nto assure the committee that a robust supply of vaccine is already available to providers and is \nready to be implemented through existing vaccine programs. The RSV season is already \nstarting and, for the first time, there potentially could be 2 important routinely recommended \noptions for RSV prevention for infants. Pregnant persons now will be able to have an informed \ndiscussion with their obstetricians and other maternal health providers, as they do for all \nroutinely recommended maternal vaccines , and make an informed decision on which option is \nbest for them and their baby. Dr. Jodar emphasized that the RSV vaccine would be a lower cost \noption and overall could result in a lower budget impact for the US healthcare system. Pfizer \nthanked ACIP and the WG for their careful deliberations and dedication to preventing infectious \ndiseases. \n36 \n \n   \n \n    \n    \n     \n      \n  \n   \n  \n   \n    \n   \n    \n   \n  \n   \n    \n     \n    \n     \n  \n \n    \n    \n    \n   \n     \n   \n \n    \n    \n      \n   \n   \n     \n    \n  \n   \n    \n     \n   \n          \n     \n  Liaison Organi zation Statements \nBrenna Hughes, MD, MSc, FACOG (ACOG) thanked the leadership of ACIP and the WG on \nbehalf of the American College of Obstetricians and Gynecologists (ACOG) for their \ncollaboration on this topic and for inviting ACOG to share its position and expert opinions \nregarding the maternal RSV vaccine. It is critical that the O B-GYN voice be considered \nparticularly as implementation considerations are discussed. ACOG remains unequivocally \nsupportive of a full recommendation for maternal RSV vaccine for pregnant individuals. This \nRSV vaccine is efficacio us and could decrease the risk of severe disease in many infants. While \nnirsevimab is clearly highly efficacious, it may not be available or may not be preferred by a \nparent or health care facility as the primary intervention. Therefore, ACOG believes it i s critical \nto ensure that pregnant individuals can access this RSV vaccine to give their newborns \nprotection after birth. As a practicing obstetrician and member of the RSV Vaccine W G, Dr. \nHughes has reviewed these data extensively, along with the other ex perts on the WG , and has \ndiscussed these data with ACOG experts and leadership. They have evaluated all of the \navailable data regarding the risk of premature delivery, and currently consider this outcome to \nbe a theoretical risk , with the benefits of vaccination outweighing the hypothetical risk of AEs. \nTherefore, ACOG feels that this vaccine should be recommended. Finally, ACOG continues to \nencourage the collection of additional data to inform future policy considerations, and look s \nforward to collaborating with the CDC and other organizations to ensure optimal implementation of strategies to decrease the burden of RSV disease in infants. \nCarol Hayes, CNM, MN, MPH, FACNM (ACNM) provided comments on behalf of the American \nCollege of Nurse Midwiv es (ACNM), the largest professional association representing certified \nnurse midwives and certified midwives in the US. ACNM sets the standard for excellence in \nmidwifery education and practice in the US and strengthens the capacity of midwives in \ndeveloping countries. ACNM members are primary care and sexual and reproductive health \nproviders for people throughout their lifespans , with a special emphasis on pregnancy, \nchildbirth, gynecological, and reproductive health. ACNM has participated actively in the ACIP and the CDC Task F orce on Maternal Immunizations and regularly update s and encourages \nmembers to recommend the 3 standard maternal immunizations throughout a shared decision-\nmaking model. The midwifery model of care puts women and pregnant people at the center of \ncare and encourages members to share scientific evidence on choice surrounding \nimmunizations so that pregnant families can make the best decisions for themselves. After \nreviewing the evidence on the safety and efficacy of the maternal vaccine, as well as the \nincidence of RSV cases in newborns and infants, ACNM strongly recommends that ACIP \nsupport the availability of this vaccine to all pregnant people from 32─ 36 weeks of gestation. \nACNM believes that pregnant individuals should be informed of the benefits and the risks of \nmaternal RSV vaccine, and the vaccine should be available to those who choose it without any \nbarrier to access, such as cost , referral , or approval by a third party. Given the rise and the \nprevalence of RSV cases among newborns, ACNM believes that pregnant people should be \nable to access a vaccine that is proven to prevent LRTD and severe LRTD caused by RSV in \ninfants from birth to 6 months of age. \n37 \n \n      \n \n  \n     \n \n  \n    \n \n    \n    \n     \n         \n      \n \n  \n   \n   \n \n  \n    \n  \n \n \n  \n   \n  \n   \n  \n    \n  \n   \n  \n    \n  \n    \n   \n   \n  \n  \n \n  \n    \n   \n \n   \n   \n   \n  \n   ACIP Discussion Points, Observations, Suggestions for RSV Vaccine \nFollowing Presentations by Dr. DeSilva and Dr. More \n• ACIP expressed gratitude to Drs. DeSilva and More for sharing the proactive plans to \nmonitor RSV vaccines. \n• In terms of an inquiry about how pregnancies with multiple gestations (e. g., twins, \ntriplets, et cetera) would be monitored since they have a risk for being preterm , Dr. \nDeSilva indicated that multiple gestations will be excluded from the initial planned \nevaluation. However, a more c omprehensive end-of-season evaluation is being planned \nand consideration will be given to how to account for multiple gestation births . \n• In response to a request about a status update on how the v-safesm monitoring of RSV \nvaccines received by persons ≥60 years of age is going, Dr. Anne H ause from the v -\nsafesm program indicated that the new version of v-safesm is still in the final stages of \ndevelopment, with a launch planned in Fall 2023 for RSV vaccines among older adults \nand anticipated for maternal RSV later in Fall 2023. Dr. Shimabukuro added that while \nthey have received a small number of reports for the older adult population, no unusual or unexpected patterns have been seen at this point. \n• Regarding whether any “back of the envelope” calculations have been done yet using different assumptions for uptake to understand what would be expected in terms of accrual of pregnancies in the VSD, Dr. DeSilva indicated that there is uncertainty about \nvaccine uptake, and they are awaiting recommendations for use, but it is anticipated that \nthey will be well- powered to detect significant differences in preterm birth within 6 \nmonths of vaccine eligibility. Additionally, there are plans to perform some preterm and stillbirth surveillance that will be separate from this plan by monthly surveillance that \nwould only be descriptive, but it would be limited to the vaccinated population and can \nbe performed somewhat more quickly. These results lack a control population, so this \nwould not statistical comparisons. \n• In terms of whether there would be monitoring of infant pertussis infection in the first 2 months of age given the lower pertussis antibodies with simultaneous vaccination with \nan RSVpreF vaccine and Tdap for which the clinical significance is unknown, Dr. \nDeSilva indicated that the VSD focuses on safety and not necessarily effectiveness of \nvaccines. vaccine effectiveness. There are other groups within the agency who have \nplans in place to study post -licensure effectiveness of maternal RSV vaccine. \n• Regarding whether there is a systematic way to capture illnesses other than RSV or \nconcomitant illnesses that occur during pregnancy that could increase risk of outcomes \nof interest, Dr. DeSilva replied that they will be capturing medically -attended events. If an \nillness rises to the level of seeking medical attention, there could be some information about concomitant infection with RSV or other infections that are not RSV. This would be \ndependent on how the provider codes what they are seeing. Consideration can be given \nto how some additional covariates potentially could be included, such as diagnosed respiratory illnesses —especially if testing is involved. \n• Regarding a comment that it would be beneficial to capture respiratory illnesses other than or concomitant with RSV and coadministration of vaccines among pregnant people, \nDr. Moro indicated that VAERS will capture other vaccines received at the time of vaccination with RSV. \n• A lesson learned from COVID -19 vaccines is that when vaccines were received in public \nsettings (e.g., pharmacy, grocery store), people often were not informed about v-safe\nsm \nand no paperwork was provided. It would be beneficial for the v-safesm team to \nimplement a campaign with the chain pharmacies, grocery stores, the American College \nof Obstetricians and Gynecologists (ACOG ), and the American College of Nurse-\n38 \n \n      \n \n  \n     \n    \n   \n    \n \n   \n    \n  \n    \n  \n \n    \n   \n \n \n    \n  \n   \n \n    \n \n  \n   \n     \n    \n    \n  \n  \n  \n   \n    \n   \n     \n    \n  \n   \n \n  \n \n   \n    \n Midwives (ACNM) to promote v-safesm. It is an incredibly valuable tool for monitoring \nside effects . \nFollowing Presentation by Dr. Hutton and Dr. Ortega -Sanchez \n• It is clear that the cost of the vaccine is a very important determinant in terms of cost -\neffectiveness, but RSV is a prevalent and costly disease. With that in mind, Pfizer was \ngiven the opportunity to speak to whether $295 was going to be the or if there would be \nany decrease in cost. \n• Donna Altenpohl , Pfizer , confirmed that the original price was $295 per dose for both the \nmaternal and older adult indications and that the Pfizer vaccine is the same product and \nformulation for both indications. The product has one National Drug Code ( NDC) and \none Current Procedural Terminology (CPT) code for reimbursement, which Pfizer took \ninto consideration. Pfizer’s pricing strategy is guided by the value that their innovation \nbrings to patients and society, with the goal of achieving the broadest possible access \nfor patients. Based on the results of the Pfizer cost -effectiveness analysis, they priced \ntheir vaccine to be both cost -effective and reflect the value that it will bring to helping \nprevent RSV for older adults and infants. As they shared with the ACIP WG, the RSV maternal  vaccine will be a lower cost option and could result in a lower budget impact to \nthe US healthcare system . \n• The expense of this vaccine is very disappointing, particularly in the context of making a recommendation for all pregnant people to receive the vaccine. It would be beneficial for the ACIP to know the cost of this vaccine to countries outside of the US to understand \nwhether it is overpriced in the US or if the price is standardized throughout the world. \n• Donna Altenpohl , Pfizer, indicated that they have a tiered pricing strategy outside the US \nthat allows the price to be contingent upon the affordability of each individual country. As they are beginning to launch the RSV maternal vaccine, the pricing will be decided at \nthat point. Given that Pfizer has not confirmed all of its pricing, it would be inappropriate \nto try to comment or speculate on that at this point beyond saying that they have not \nfinalized the price depending on whether there is separate pricing for the older adult \nindication and the maternal vaccination. The global pricing strategy is tiered based on \nthe affordability of each and every country, with the goal of making sure there is affordable access for all eligible patients. \n• Slides 6 and 7 in Dr. Hutton’s presentation show the difference in waning between 1, 6, and 9 months. Since maternal antibodies fade away by 6 months, it was not clear which \nof the 2 slides was a more realistic representation of efficacy and whether there would \nstill be antibodies between 6 and 9 months or a dramatic decrease at 6 months. There \nare maternal antibody data for other illnesses. \n• Dr. Hutton replied that during their conversations, they thought 6 months was a \nconservative assumption and that there are a lot of data to suggest that antibodies would be gone after that. Because that is not known for certain, they had a couple of different scenarios. \n• Referring to Slide 15 in his presentation, Dr. Ortega- Sanchez added that the 2 \nassumptions about duration of protection were shown side -by-side. The pink shaded \narea in each model denotes a higher level of uncertainty of the waning assumption beyond available Phase 3 data. There are no data that that support whatever the \nvaccine efficacy to say that there will be some protection. The CDC model assumed a \nmore conservative assumption to minimize the uncertainty about whatever vaccine protection will be received after 6 months. \n39 \n \n       \n  \n    \n    \n     \n   \n  \n  \n \n    \n   \n \n   \n  \n \n  \n   \n    \n     \n  \n    \n  \n  \n   \n \n  \n  \n    \n \n \n      \n    \n    \n  \n    \n  \n \n    \n \n  \n    \n \n    \n   \n  • To the point about other maternal antibody data, Dr. Fleming Dutra confirmed that there \nare data from other vaccines (e.g., Tdap, influenza, and COVID vaccines) that indicate \nthat post -maternal effectiveness of these other vaccines usually has waned by 6 months. \n• It is important to understand that while maternal antibodies can persist in the infant as late as 18 months, the protective level of antibody is the issue. With other vaccines, the antibody level is significantly reduced after 3 to 6 months. Although some antibodies can \nbe detected, the levels probably are too low to be considered efficacious for whatever \ndisease one is trying to prevent. \n• Dr. Jessica Atwell, Pfizer, provided more context regarding the data that inform antibody persistence in infants beyond 6 months. In addition to the data from Pfizer’s Phase 3 \nclinical trial, they also have data from their Phase 2b study that measured antibody \npersistence in infants out to 6 months and compared those levels between infants born to vaccinated individuals and unvaccinated individuals. They were significantly higher \namong infants born to vaccinated individuals compared to infants born to women who \nreceived placebo in the Phase 2b trial. They used the half -life of antibody decay from \nthose data to then extend the potential antibody persistence beyond the 6- month time \npoint. That modeling, which was shared with the WG, showed persistence even beyond 9 months out to 12 months. Because there is no correlative of protection for RSV, it is it \nis difficult to make direct assumptions about how those antibody levels may translate, \nbut certainly Pfizer has data to support persistence in infants beyond 6 months, which \nwere critical for informing th e assumption about persistence of antibodies and potential \nbenefit. If a pregnant person r eceived RSVpreF 3 weeks before delivery, the practitioner \nwould have to weigh the question of what the additional value would be of adding \nnirsevimab on top of that. If it is known the infant will definitely receive nirsevimab, it would be reasonable to consider the value of adding RSV preF on top of that. \n• Regarding an inquiry about whether, with the information about the monoclonal antibody and the vaccine on top of that having some benefit but at a very costly rate, there ever \nwould be a scenario in which monoclonal antibody could not be given to infants and \nthere would have to be reliance on mother ’s immunization, there is no known \ncontraindication to giving both. Dr. Hutton said it would be a reasonable intuitive \nassumption that there would be some added incremental benefit. Dr. Long added that it was very perceptive for ACIP members to be asking these questions, and that later \npresentations would later “thread the needed” pertaining to what circumstances would \nallow a physician to give nirsevimab after a pregnant person has been properly \nimmunized. \n• Hearing that the cost per QALY for RSVpreF is about $400,000 at a dose of $295 per \ndose and recalling that during the August 3, 2023 ACIP meeting the cost per QALY for \nnirsevimab was $100,000 at a cost of $495 per dose , the difference was unclear. \n• Dr. Hutton responded that there is a lot going on. The major element in the simulation \nmodeling of nirsevimab is that efficacy is slightly better at the beginning, so slightly higher efficacy is one difference. Another difference is that nirsevimab can be given at \nthe peak of the RSV season. An infant born in April, May, June, or July would be given \nnirsevimab to have peak efficacy during the season. Those are a couple of the factors \nthat affect the differences in the cost -effectiveness of nirsevimab versus what was \nshown regarding RSVpreF during this session. The cost- effectiveness of RSVpreF looks \nmuch better when it is given right before the peak of the RSV season when it will confer \nthe highest levels of efficacy. \n• Regarding an observation that there did not seem to be a comparison of the cost of \neither the pregnant person receiving maternal vaccine or the baby receiving nirsevimab, Dr. Long indicated that there are no head- to-head comparisons because these are \n40 \n \n  \n \n \n  \n  \n    \n \n  \n   \n  \n    \n \n   \n  \n  \n     \n     \n  \n    \n    \n     \n  \n \n   \n    \n   \n  \n   \n    \n   \n \n       \n      \n  \n   \n    \n   \n      \n    \n      \n      \n     \n     \n       \n   \n  \n        \n   standalone products that have been assessed. The recommendation for a possible vote \nduring this meeting pertained on to the vaccine product. However, that did not preclude \nthe possibility of occasional unusual situations in which a vaccine would be given before \ndelivery followed by nirsevimab after delivery. Dr. Jones added that the base case \nscenario of giving the vaccine alone is the cost -effectiveness when not giving nirsevimab \non top of it. E ssentially, it was being presented as if either RSVpreF or nirsevimab was \ngiven. \n• In terms of an inquiry about projected uptake rates, Dr. Hutton responded that the UM-\nCDC model assumed 50% uptake. A nice round number like 50% typically suggests that \nit is an assumption. There are limited data about uptake at this point beyond the surveys \nthat have asked people about their intent, which suggests that 50% might be a \nreasonable assumption. Given the anticipated implementation challenges, Dr. Long \nthought 50% uptake would be optimistic for the vaccine this year. \n• In an ideal world, it seemed that the precision public health approach of considering seasonality would be the best -case scenario. However, there are issues of the \ncomplexity of implementation in terms of such tight timing, the cost and burden on teams \nwho are trying to deliver the vaccine in a precise manner, and so forth—even if that \nprecision might lead to a better investment in health overall . \n• ACIP members continued to struggle with the cost of RSVpreF vaccine. While they \nacknowledged and understand that the studies were expensive and Pfizer needs to \nrecoup their costs, $295 per dose is a hard cost to swallow. It is known that the higher the price of a vaccine, the higher the disparities. \nFollowing Presentations by Dr. Fleming- Dutra,  Dr. Jones, Dr. Peacock \n• To set the stage for this discussion session, Dr. Long made a few comments on the underpinnings of the WG considerations and recommendations for ACIP’s consideration. The WG was very concerned about the imbalance in prematurity, especially in the \nshadow of the GSK vaccine that was not pursued. The WG likely would not have come \nto consensus on a non -suffixed recommendation for 24─36 weeks. “Non- suffixed” \nmeaning with shared clinical decision- making. The data on vaccination at 32─36 weeks \ngestation, coupled with the information that the prematurity that occurred in the trials was an average of 4 plus weeks after immunization was not associated with reactogenicity at \nthe time of immunization, made the WG more sanguine with 32─36 weeks gestation. \nThey thanked the FDA for making that restriction and not having the WG have to do that as a first potential restriction. The second restriction of the seasonal administration, \nalthough this is not terribly popular, goes with the influenza season. That also, for most of WG, was based on a safety consideration. Given the potential risk of prematurity, \nyear-round administration may not benefit the infants born in April ─September. That was \nthe reason for that restriction. Regarding cost in terms of the base case, she did not \nthink the WG would have come to consensus for a recommendation. It was only the \nseasonal use that, while it may be somewhat off -putting to some, that was the only way \nin which this could get down to a QALY that was acceptable in their minds or similar to \nother vaccine or preventions that allowed the WG the ability to present a non- suffixed \nrecommendation to the ACIP. In addition, there are no head- to-head trials of these \nproducts or of safety. The WG thought that there would be mitigation of the potential risk \nof prematurity, et cetera. In terms of how ACIP considers the WG’s very restricted \nsuggestions for the use of nirsevimab after the receipt of appropriately timed vaccine, \nthat the ACIP takes into consideration that these are both “antibody paint ” and that the \n“antibody paint ” will wear off. They do not change the epidemiology of RSV disease and \nthe goal is not to prevent RSV infections in every individual. This can only r educe the \n41 \n \n     \n   \n   \n    \n   \n      \n \n       \n   \n   \n \n  \n   \n  \n \n  \n   \n \n   \n      \n    \n     \n   \n  \n \n   \n  \n    \n   \n   \n \n   \n   \n    \n     \n \n  \n  \n   \n  \n  \n            \n   \n  \n \n  \n    \n  morbid consequences of RSV by a certain degree. Pediatricians and others already \nhave already expressed concerned about the cut -points for nirsevimab and the vaccine. \nThe cut -points are based on data. Because this is not a vaccine that will chang e the \nepidemiology, prevent herd, provide long -term protection, the cost must be acceptable \nas possible because these are extraordinarily and probably unreasonably priced \nproducts. The WG would say , “Bring on the competition to bring the costs down in the \nUS.” \n• Dr. Talbot said she thought this might be the most complicated vaccine recommendation \nfor young adults that ACIP has had in a long time. She is worried about the complication \nof the time period. While influenza and COVID vaccines are given during that season, \nthey are given to everybody regardless of where they are in their pregnancy. She also is \nconcerned that in the adult world if someone gets the same vaccine twice, the same \nvaccine may be paid for twice. That is, if a mother has gotten the RSV vaccine but is confused because she received 4 vaccines, 2 vaccines, or 3 vaccines and the \npediatrician is left in a position to give the child the antibody, someone is going to have \nto pay because that is double- dipping since ACIP would be recommending one or the \nother. She wondered what the benefit would be of this vaccine if every child would be \ngiven antibody. \n• Dr. Long emphasized that it is always good to have 2 products . It is not known what \nmanufacturing will be like in the future or if after the first year of use, one or the other \nwould make them more hesitant to use one or the other. \n• Dr. Poehling said that in speaking to parents who have recently given birth, some would \nprefer to take a vaccine rather than have their child get a shot. She also has had cases \nrecently, including one in which the father of the child had a significant bleeding disorder, \nwho did not want the child to have any sticks for any reasons because it would be \nunknown at that point whether the child was going to have a bleeding disorder. There \nwill be multiple cases like that. T here is a lot of complexity . Clearly document ing the \ninformation so that everybody knows what has and has not been received is going to be \nextraordinarily important. It also builds upon what has been said repeatedly during \nprevious meetings that having an immunization registry for all is desperately needed. \nShe recalled that Dr. Peacock ’s presentation showed that 52% of persons who are \npregnant have private insurance, 41% have Medicaid, and 4% are self -pay. She thought \nthey needed to dive deeper into this. The ACA states that private insurance has to cover \nthe vaccine, but that is not immediately. She wondered whether there are any data on \nhow many private insurances are paying for the RSV vaccine for adults ≥60 years of \nage. \n• Dr. Grubb (AHIP) said that while she did not have those data readily available, she \nwould try to obtain the information for the ACIP. \n• Dr. Poehling emphasized the importance of the people listening to understand that there is a delay before insurance companies actually pay for the vaccine. In addition, it was her understanding the 317 funds recently have been decreased, which could impact \nindividuals 18─19 years of age who do not fall under Medicaid or the VFC program. \n• Dr. Peacock confirmed that while the 317 funds have not decreased, the re is limited \navailability of funds since there are more vaccines that potentially could be paid for \nuninsured adults through this program. For context, 317 program funds are allocated t o \nall immunization awardees so that they can purchase some vaccine. Typically, this \nprogram is used for uninsured adults , sometimes fills in gaps related to children, and \nalso is used for outbreak funds. \n42 \n \n    \n \n  \n  \n \n       \n     \n      \n   \n    \n \n    \n   \n  \n  \n \n \n     \n      \n \n \n  \n  \n  \n \n   \n  \n \n   \n   \n  \n \n       \n    \n  \n   \n   \n  \n \n  \n \n    \n \n  \n    \n     \n  \n  \n   \n  • Ms. Hance (CMS) confirmed that Medicaid will cover t he vaccine for adults who have \nMedicaid who are covered under a CDC ACIP recommendation. That coverage is \nseparate from the 317 program. \n• Dr. Sanchez said he favored a shared clinical decision- making recommendation \nbecause there are 2 options that need to be discussed with the pregnant individual. The \nfirst would be by her obstetrician who will need to discuss vaccination at 32─36 weeks \ngestation, but also will need to discuss that the other option is nirsevimab. Pediatricians who will be taking care of the infants would have to tell the mother the baby cannot get \nnirsevimab if she chose to receive the RSVpreF vaccine. Regardless of whether those \ndiscussions are easy or hard, they must be had. With that in mind, he asked whether \nthere would be an option to vote on shared clinical decision- making. \n• Dr. Lee requested that the team display the proposed vote language. She said that in \nher opinion, every recommendation should be a shared decision similar to all medical \ncare that clinicians provide. To her, the distinction about the recommendation was not \nabout whether the process occurred. It was more about a universal recommendation \nversus more of a selective recommendation. Even a full recommendation would not \nmean that this discussion should not happen. In fact, this discussion should occur with every pregnant person to make sure that they are aware of the options. She did not think \nthat a shared clinical decision- making recommendation would change that. She noted \nthat while there always is an opportunity to amend proposed voting language, she would \nlike to focus on the displayed proposed language from the WG to make sure everyone \nhad an opportunity to comment. \n• Ms. Bah ta agreed that the feasibility of having 2 products that would be given at 2 \ndifferent times to 2 different audiences would be challenging. Colleagues in her own health department are struggling with how to implement nirsevimab and how to reconcile \nthat if the RSVpreF vaccine also is recommended. She also cautioned that because \nRSVpreF is being implemented among older adults and the vaccine is very costly, there could be competition over a limited supply and/or limited availability if maternal vaccine \nis recommended. Given that there were 2 wonderful options, it was extremely difficult not \nto be supportive of the recommendation as proposed. While she supported it and agreed that every vaccine provided to patients should be explained, she wanted to highlight her \nconcern about the feasibility of implementation. \n• Dr. Loehr strongly supported the seasonal nature of the recommendation. He noted that one insurance company that typically has been slow to implement recommendations is \ncovering nirsevimab effective immediately, and he expressed gratitude to all of the \ninsurance companies that are doing likewise in order to get it administered within this \nseason. He asked whether the WG considered adding a sentence stating that this \nrecommendation is for pregnant persons not intending for their infants to receive \nnirsevimab, or if there was a reason not to include such language. For instance, if he \nknows an infant will receive nirsevimab, he would not recommend maternal RSV \nvaccine. \n• Dr. Poehling noted that one insurance in North Carolina has agreed to pay for nirsevimab in the outpatient setting. They are still awaiting word on the inpatient setting. \nShe continues to remain concerned about the cost and who is going to cover it. \n• Dr. Long responded that including that language might be a tacit implication that ACIP \nmight not prefer this vaccine. At this point this year, not knowing more than what they do \nabout efficacy and safety, they probably would not want to do this. She agreed with others that while it did not rise to the level of a policy decision, this absolutely should be \na shared decision between a doctor and patient. That is best addressed in the clinical \nconsiderations. If anyone was wondering why in the world a decision ever would be \n43 \n \n  \n \n    \n   \n  \n  \n \n    \n \n     \n \n  \n   \n  \n   \n \n   \n \n   \n   \n   \n  \n  \n  \n  \n     \n    \n \n   \n    \n  \n  \n  \n \n  \n      \n  \n \n   \n \n          \n     \n             \n \n     \n   \n   \n    \n made to withhold nirsevimab or give the vaccine on top of the plan for nirsevimab, they \noccur at different times in the pregnancy and there may be compelling reasons. For \nexample, if it was identified in utero that a baby had significant congenital heart disease \nand no safety issues had been identified, she would want to save that person for \nnirsevimab and not risk any potential AEs by giving the vaccine during pregnancy. While \nshe favored the spirit of Dr. Loehr’s suggestion, she did not favor including it in the language per se. \n• Dr. Sanchez suggested that there could be another angle. For example, a fetus diagnosed with severe congenital heart disease or other malformation may stay in the \nneonatal intensive care unit (NICU) for an extended period of time. While every effort is \nmade to prevent RSV infection in the NICU, it does occur. If nirsevimab is not going to be given until discharge, this could be a compelling reason to vaccinate the pregnant \nperson to ensure that the baby benefits from maternal antibody at least through the time of discharge. In any case, they have recommended that nirsevimab be given irrespective \nof whether the mother was vaccinated. He thought that should be kept as a clinical \nconsideration. \n• Dr. Long expressed gratitude to Dr. Sanchez for raising this issue and stressed that he \nhas been instrumental in helping the WG understand all aspects, especially of \nperinatology. However, she did not think monoclonal antibody or anything else should be \ngiven in the NICU to protect infants in the nurser y. Infection control should do that. If \ninfection control fails, then monoclonal antibody can be given. She also thought protection from maternal antibody could be long gone before an infant with severe congenital heart disease was discharged from the NICU . \n• Dr. Sanchez clarified that he was not suggesting giving nirsevimab to infants in the NICU until the time of discharge and agreed that infection prevention and control is preferable. \nHowever, some infections do occur. His thinking was that if a term baby had maternal \nantibodies, at least for the first several weeks before they have their surgery or bypass, \nthat it might also be beneficial, and the risk should be low because of infection \nprevention practices. \n• Dr. Kotton expressed her support for the proposed recommendation language as \npresented. She thought it was easy to understand and that it is imperative for the public to clearly understand what the ACIP is recommending. Shared clinical decision- making \nhas been very confusing, so she would not support that. \n• Regarding the shared clinical decision- making comments, Dr. Hughes (ACOG) \nemphasized that obstetricians are highly experienced with and routinely perform counseling for all patients who receive vaccines, and this would be no different. She \nagreed with Dr. Long’s assertion that for this reason, the recommendation did not rise to \nthe level of shared decision- making policy and she would support the full \nrecommendation on behalf of ACOG. \n• Dr. Talbot pointed out that it seemed this recommendation was telling their obstetric \ncolleagues that all pregnant persons should receive the RSVpreF vaccine between \n32─36 weeks and unless the fetus has a condition , and the infant then could not get \nmonoclonal antibody if the pregnant person was vaccinated. If a pregnant person was \n32─36 weeks near the end of the RSV season, it was not clear what this would mean for \nthe infant in terms of qualifying for monoclonal antibody. \n• Dr. Jones clarified that there was voting language and the clinical considerations. The \nWG discussed all of this at length and there were some differing opinions among the \nWG members. The majority felt that the voting language proposed for the vaccine would \nbe appropriate. The voting language for the vaccine was to convey that either product is \nrecommended and administration of both is not needed. The decision of which option to \n44 \n \n  \n  \n   \n   \n   \n  \n  \n    \n  \n   \n \n      \n \n    \n  \n  \n  \n     \n   \n   \n     \n    \n     \n     \n \n   \n   \n \n   \n  \n   \n    \n   \n   \n  \n     \n   \n   \n   \n    \n  \n \n \n    \n    \n   \n \n    \n choose should occur at the time when deciding whether to vaccinate the pregnant \nperson. \n• Dr. Long added that if the pregnant person chooses the vaccine, then the practitioner would indicate that at birth, the baby would not need nirsevimab except in rare \ninstances. It is true that the mother has a choice, but it is merely a choice like choosing different colored shoes with different heights of heels. Some will choose to protect their \ninfant by vaccinating themselves, and others will choose for their baby to have \nnirsevimab. Given the anticipation that this season will be messy in terms of who \nreceives what and who pays for what, whether there are risks, and what the \neffectiveness of these products will be , the WG wanted to offer the best possible \naccommodations . \n• Dr. Jones confirmed that all of the details that should occur in discussions with patients \nwould be covered in the clinical considerations and emphasized in the suite of educational materials, the MMWR , the Vaccine Information Statement (VIS), et cetera. \nThis includes specification of the rare situations in which there are insufficient antibodies \neither because they were not produced after vaccination in a pregnant person or there is \ndecreased transplacental transfer. For those who will have potential waning of \nantibodies and waning protection by the time RSV season peaks, because the \nrecommendat ion would be from September─January and infants would be born to those \nmothers during the RSV season. \n• With regard to the vote, Dr. Lee said she believes this is a good vaccine product with a \nfavorable benefit -risk balance, particularly with the efforts to mitigate potential risks. This \nis an excellent option to protect infants from hospitalization. If there was not a \nmonoclonal antibody available such as nirsevimab, she thought the cost- effectiveness \nconversation might have been slightly different. In terms of the struggle with cost -\neffectiveness, which always is an important domain, the decision is sensitive to this \ndomain.  The intervention itself and maternal vaccine development in general are \nincredibly important investments with regard to future directions with the US vaccination \nprograms as a country . She wanted to recognize that cost -effectiveness is about the \nvalue of the vaccine and the value of the investment. The proposed vote the WG asked \nthe ACIP to consider in terms of seasonal dosing of RSV vaccine seemed extremely helpful to ensure that they are making the investment as worthwhile as possible. The \ncost- effectiveness ratio is still high -ish, recognizing that they do not have an explicit \nthreshold by any means. This will be one of the more expensive interventions the ACIP \nhas recommended,  so she wanted to call out that seasonal dosing is a way to at least \nget into a more reasonable range. Recalling an earlier conversation, she said she \nthought the ACIP’s role is only to comment on the value of this vaccine in the US. As \nthey learned during COVID, having products available such as these RSV vaccines or \npassive immunization become more available to low -and middle- income countries that \nmight not otherwise have access is som ething they need to consider. She encouraged \ntheir manufacturing sector colleagues to consider how such innovative products can be \nmade available in countries at an affordable price, recognizing that each country is \ndifferent, but also recognizing that there is a greater responsibility from a public health \nperspective. \n• Dr. Sanchez said he thought one of the problems was that it was impossible to consider \nthis vaccine in isolation, because the fact is, there is another product. Unfortunately, there is not a head- to-head trial comparison of the 2 products with respect to either \nefficacy or effectiveness. Discussions must be had with the pregnant person because there are options, and each medical decision should be shared decision- making. There \nshould be a lot of education about both products. \n45 \n \n   \n   \n    \n   \n     \n     \n  \n   \n \n     \n           \n \n  \n  \n    \n  \n  \n    \n    \n     \n \n \n   \n   \n  \n    \n  \n \n   \n   \n    \n     \n     \n    \n     \n        \n \n  \n  \n \n \n   \n  \n \n   \n  \n  • Dr. Loehr said he wanted to go on record that he believes an infant receiving nirsevimab \nis better based on the evidence that it has better efficacy. It also is more cost -effective. \nTherefore, he did not want it to be an equal representation. He recognized that they \nwere not going to make a preferential  statement and that a lot more data would \naccumulate over the next couple of years to determine in the long- run which is better. He \ndoubted they ever would have head -to-head information. If he was presenting this to a \npregnant person , he would recommend giving nirsevimab to their child if that is what \nthey wanted. If not, then the vaccine would be another option. This is just a small nuance. \n• Dr. Sanchez emphasized that to him, the signal for prematurity was a major concern for him and the WG. The FDA did help with this issue by approving vaccine administration \nat 32─36 weeks gestation. Nevertheless, mothers should be made aware that this needs \nto be monitored and there will be post -licensure and post -recommendation surveillance. \n• Dr. Bell emphasized that one complication is going to be that the pregnant person is \nlikely going to be seeing a different doctor during pregnancy than the doctor who will be \ntaking care of their child. Tools must be made available quickly to physicians, which is \nsomething the partners and professional organizations can help to facilitate. It is difficult to make a choice without all of the tools. \n• Dr. Talbot emphasized that her feeling was that this would be incredibly complicated. There is a great option that can be given to children, which will protect more children and \nthat is more cost -effective. The vaccine seems like an incredibly complicated, way out of \nthe atmosphere expensive option that would not result in much benefit and would \nincrease confusion in terms of whether the pregnant person received vaccine or \nreceived it and then delivered too early. She did not believe this would improve care and \nwould make providing care more difficult. If they simply say the child should receive the \nmonoclonal, the recommendation would be a very simple and cost -effective mechanism. \nWith an adult immunization registry in every state, using this mechanism may put \nchildren at risk and/or leave the parent stuck with a $500 bill because only one method \nwould be paid for. \n• Dr. Poehling emphasized that as a newborn provider, she evaluates the charts of the moms and babies. It may not be easy, but it is definitely doable. \n• Dr. Hughes (ACOG) emphasized that it is absolutely routine for obstetricians to collaborate with their pediatric colleagues to review maternal charts. It is done every day \nregarding testing like hepatitis B testing. Those results are always communicat ed. While \nACOG recognizes that there are some complexit ies to ensuring that the charts are \ncomplete related to receipt of vaccine, it is quite doable. Also acknowledging the fact that \nthis is fairly complex , ACOG and its colleagues at the Society for Maternal Fetal \nMedicine, plan to partner with other entities like AAP, AAFP, and ACNM to ensure that \nthere is a solid implementation strategy to assure that these challenges are met. \n• Dr. Poehling made a motion to approve the language as presented, which Dr. Loehr \nseconded. \nFollowing Dr. Santoli’s Presentation \n• For Table 1, it was suggested that the additional language be revised to read, “whose mother did not receive the vaccine, whose mother’s vaccine status is unknown, or who \nwas born within 14 days of maternal vaccine.” \n• Dr. Santoli indicated that the language could be updated for clarity. \n46 \n \n  \n \n  \n \n    \n   \n  \n  \n    \n  \n  \n      \n \n \n \n \n \n \n \n        \n      \n      \n   \n    \n     \n   \n    \n  \n  \n  \n  \n   \n     \n   \n   \n \n    \n   \n   \n \n \n  \n \n \n    \n   \n     \n  \n    \n    PUBLIC COMMENTS \nOverview \nThe floor was opened for public comment on September 22, 2023 at 2:30 PM ET. Given that \nmany more individuals registered to make oral public comments than could be accommodated \nduring this meeting, selection was made randomly via a lottery. Dr. Lee provided a gentle \nreminder that the ACIP appreciates diverse viewpoints that are respectful in nature and issue-\nfocused rather than comments directed at individuals. The comments made during the meeting \nare included in this document. Members of the public also were invited to submit written public \ncomments to ACIP through the Federal eRulemaking Portal under Docket Number ID CDC -\n2023- 0076.  Visit http://www.regulations.gov for access to the docket or to submit comments or \nread background documents and comments received. \nPublic Comments \nMr. Paul Hennessy \nIndividual \nHi. I was supposed to comment at the meeting on the 12th, but I think only 1 person spoke \nduring public comments. So, I definitely urge you to look into that issue. I know there are a lot of \ncommenters who didn’ t get to speak. But, yeah, I ’m here to talk about the future of vaccine \nrollouts, not just RSV, but COVID as well. You know, I thank the ACIP for approving those 3 \nvaccine options last week. But a once-a- year shot does not go far enough, considering \nprotection wanes after about 5 months and there’ s multiple waves of COVID per year. COVID is \nnot the flu, so a shot schedule like the flu just isn’ t working. A once -a-year vaccine just isn ’t \nenough to protect us from a virus that fuses brain cells, causes blood clots, is linked to diabetes, \ndementia, and more. Furthermore, COVID and RSV are airborne illnesses , so the vaccine- only \napproach doesn’ t properly reduce transmission as much as it can. You know, clean- air tech and \nmasking must be encouraged along with vaccines and even required in places like medical \nsettings. Pediatric approval for the Novavax COVID vaccine is also needed as soon as possible. \nYou know, I definitely appreciate that the RNA has been approved, but children, like adults, deserve the choice. Novavax was shown to wane less quickly than mRNA and offer broad \nimmunity against variants. Successive doses actually enhance protection as well as offer some \nupper respiratory protection. Children deserve this excellent choice as well. Finally, just going \nforward, I ’d definitely like to urge ACIP to approve vaccines before surges . That includes both \nCOVID and RSV. Moderna ’s and Pfizer ’s COVID vaccines were ready, and I believe submitted \na number of months ago , but it took until September to get approval. It ’s so important to approve \nboth COVID and RSV vaccines before the school year so children are protected going to \nschool. Thank you. \nJane Hull, PT, MPH \nTRAIPAG \nI’m Jane Kaplan H ull I’m speaking on behalf of TRAIPAG, which is a patient advocacy group \nwhose members are transplant recipients and/or are immunocompromised. We strongly urge \nthe committee to recommend the RSV maternal vaccine and to add it to the Vaccines for \nChildren Program so as to immunize the child through the mother. Our TRAIPAG Advocacy \nGroup commends the committee for placing the mAb, nirsevimab, not sure I ’m saying that right, \non the Vaccines for Children Program and taking the groundbreaking step of recommending \n47 \n \n   \n \n    \n   \n     \n      \n   \n   \n \n \n \n  \n \n     \n   \n   \n  \n \n   \n  \n    \n    \n  \n    \n   \n   \n  \n  \n    \n    \n \n      \n    \n   \n    \n    \n   \n  \n  \n    \n   \n    \n    \n      \n    \n  passive immunization, which ensures that it will be covered . We u rge the committee to do \nlikewise if and when a monoclonal antibody or antiviral prophylaxis against COVID is authorized \nby the FDA. This would be especially crucial to the population of immunocompromised people \nwho do not respond to vaccines and will greatly benefit from effective vaccine or prophylactic \ntreatments that can both save lives and improve quality of lives for those affected. We would \nalso hope that the committee in future deliberations recommend the RSV vaccines, not just for \nthe 60 and over, but give access to the RSV vaccines for those who are immunocompromised \nor high risk and those living or working with vulnerable populations. Thank you for giving me the \nopportunity to speak. \nDr. Roselie Bright, ScD\nCOBID Safe Maryland \nHi. Good afternoon. I’m Roselie Bright. I have a Doctor of Science in Epidemiology and had a \n30-year career as a Federal Medical Product Epidemiologist. For meaningful consideration of \npublic input, the substantive materials for CDC Advisory Committee meetings, the slides, whit e \npapers, et cetera, should be available to the public for at least a week before the meetings to allow adequate time for thoughtful, in- depth public review and comment. People who have \nalready signed up for comment should be notified the same day the materials become available. \nThe oral public comment session needs to be expanded to at least an hour and occur before \nmotions and votes. RSV vaccines have been approved by the FDA for older adults and infants a \nmonth ago. The one under consideration today was also approved by FDA for pregnant people and infants. I support expanding the use of RSV vaccines and have several points regarding the \nspecific RSV vaccine under consideration and RSV vaccines in general : 1) for non- pregnant \nadults, the RSV vaccine has been approved for people 60 years old and over. I urge the \nsponsors to quickly study the usefulness of the [ inaudible] all people at high- risk from RSV and \nall people in professions and situations that often interact with people who are at high risk of RSV, that is, health care workers, patients and visitors, and childcare and school staff and \nchildren, etc. ; 2) RSV infections have risen significantly year over year during the COVID -19 \npandemic. If the rise is due to immune damage from COVID -19, the potential benefit of offering \nthe [inaudible] ; 3) Three, RSV circulation is seasonal, typically starting during the fall and \npeaking in the winter. The peak RSV hospitalization season has been moving to earlier in the calendar year in the specific surveillance areas of the US. Please offer the RSV vaccine in the \nsummer to prevent the surges that have recently been starting in September ; 4) because getting \nthe RSV vaccine is recommended for a narrow window of pregnancy, 32 to 36 weeks of \ngestation, availability for pregnant people needs to be speedy to help as many pregnant people \nas possible this fall ; 5) RSV vaccine efficacy wanes. That’s fine for pregnancy and infancy. \nHowever, please consider recommending that pregnant people should be revaccinated during each subsequent pregnancy. In addition, older adults should be offered semiannual \nvaccinations ; and 6) RSV is part of the trio of airborne viruses that CDC is already campaigning \nabout. While the COVID -19, influenza, and RSV vaccines reduce the risk and severity of \ninfection, they don’ t entirely eliminate infections and some people should not take them. I ask \nCDC and the vaccine sponsors to include other precautions against airborne viruses in your \npublic messages, including N95 or higher quality masks, otherwise known as respirators, and \nair cleaners with h igh-efficiency p articulate air (HEPA ) filters and fresh air ventilation [inaudible] \nespecially if those that vulnerable patients must attend as staff or clients, including health care \nfacilities, schools, and prisons. Thank you for this opportunity to comment. \n48 \n \n  \n \n \n      \n  \n \n   \n \n \n \n \n \n \n  \n \n    \n  \n \n     \n    \n \n \n             \n          \n        \n \n \n \n  \n \n   \n \n \n   \n \n       \n     \n    \n    \n \n              \n          \n        \n \n  VOTES \nDr. Grace Lee (ACIP Chair) requested that the language for the votes be displayed for the \nrecommendation and VFC votes. \nVote #1 RSV Maternal RSV Vaccine Recommendation \nMaternal RSV vaccine is recommended for pregnant people during 32 through 36 weeks \ngestation, using seasonal administration, to prevent RSV lower respiratory tract infection in \ninfants. \nMotion/Vote #1 Maternal RSV Vaccine \nDr. Poehling made a motion to approve the proposed Vote #1 recommendation stating , \n“Maternal RSV vaccine is recommended for pregnant people during 32 through 36 weeks \ngestation, using seasonal administration, to prevent RSV lower respiratory tract infection in \ninfants. ” Dr. Loehr seconded the motion. No COIs were declared. The motion carried with 11 \naffirmative votes, 1 negative votes, and 0 abstentions. The disposition of the vote was as \nfollows: \n11 Favored: Bahta, Chen, Daley, Lee, Loehr, Long, McNally, Poehling, Sanchez \n1 Opposed: Talbot \n0 Abstained: N/A \nVote #2 VFC Resolution Maternal RSV Vaccine \nApprove the Vaccines for Children (VFC) resolution for RSV maternal vaccine. \nMotion/Vote #2: VFC Resolution Maternal RSV Vaccine \nDr. Loehr made a motion to approve the proposed Vote # 2 recommendation for the VFC \nResolution stating , “Approve the Vaccines for Children (VFC) Resolution for RSV maternal \nvaccine. ” Dr. Poehling seconded the motion. No COIs were declared. The motion carried with \n11 affirmative votes, 1 negative votes, and 0 abstentions. The disposition of the vote was as \nfollows: \n11 Favored: Bahta, Chen, Daley, Kotton, Lee, Loehr, Long, McNally, Poehling, Sanchez \n1 Opposed: Talbot \n0 Abstained: N/A \n49 \n \n  \n  \n \n   \n   \n     \n   \n    \n     \n \n    \n \n       \n    \n    \n    \n     \n   \n \n       \n      \n \n \n    \n     \n       \n  \n     \n    \n     \n   \n    \n  \n    \n      \n    \n  \n \n      \n   \n \n     \n     \n  \n     \n     \n      \n    \n    \n     \n       Discussion Points : Voting Members \nDr. Poehling emphasized what an exciting day this was because throughout her career, RSV \nhas been a difficult disease, given that there have been no options beyond supportive care \ntreatment. There were over 1.5 million outpatient visits, over half a billion ED visits, and 58 ,000 \nto 80,000 RSV hospitalizations last year, which was a dramatic example. The vast majority, \nalmost 80% , of children less than 2 years of age have no underlying conditions. There is nothing \nsimple about this RSV vaccine or nirsevimab, but they both offer hopes. They have done this \nbefore with COVID vaccine. She think s that if everybody is willing to chip in and do their part , \nthis is feasible and will improve the well -being of many families throughout the nation. \nDr. Bell said she wanted to take advantage of her gray -haired status and reflect for a moment \non the issue of complicated recommendations for which implementation is unclear and there are \na lot of challenges. To Dr. Lee’s point earlier that in looking back over the decades, these types \nof recommendations have provided opportunities for innovation, availability of options, and \nimprovements over the longer term even if the beginning is extremely bumpy . This is another \nexample that perhaps will lead to improvements in physician education, patient decision-\nmaking, communication between the obstetrical and pediatric worlds, and addressing \ndisparities. Even though ACIP members may be feeling at the moment that this is very \ncomplicated and will be difficult to implement, in the longer term it will result in new options that \nwill improve children’s health. \nDr. Sanchez agreed completely. He thought the discussions throughout the day had been \nextremely helpful because he certainly has struggled with his decision throughout the time that \nhe has been on the RSV WG. He has fluctuated back and forth, but thought the day’s \ndiscussions steered him clearly through the amazing work that has been done. There are \nchallenges and complexities, but there are options for mother s and HCPs . Physicians also have \npersonal preferences that are part of the physician- patient discussion. He thought the options \nwere great. Pediatricians , infectious disease specialist s, and neonatologist s have to prevent \nserious RSV disease in babies. He thought it was fantastic that they had achieved this vote , as \nwell as the nirsevimab vote. He could not have imagined better options for infants and children , \nwhich is what they have been striving for —especially for high- risk babies. He urged more \ndiscussions with obstetricians, mothers ’ healthcare provider s, and pediatric family practices. \nJust like they need to know the mother ’s syphilis, HIV, and hepatitis B status, they also will need \nto know whether the mother received the RSV vaccine. Hopefully, this will ultimately improve \ncare and communication with obstetric providers. \nDr. Brooks said he was reflecting back on the days when they thought PCV discussions were \ncomplex . Yes, RSV has been very complex. However, they likely are going to have more \ncomplex decisions to make moving forward. Dovetailing on what Dr. Sanchez said, one of the \nthings that struck him was that a large number of obstetricians feel uncomfortable with \ndiscussing vaccine decisions. Looking at the schedule, there are 4 vaccines that theoretically \ncould be available or needed for a pregnant person (RSV, COVID, influenza, and Tdap) \nbetween October through March. That is half of the year —a significant amount of time where \nthere are going to be some really interesting discussions. They need to lean on the American \nCollege of Obstetricians and Gynecologists (ACOG ) to work with their members to feel more \ncomfortable with these discussions. To him, one of the benefits is a fundamental concept of \nvaccination, which is that generally speaking, the ideal is for a person to get vaccinated at the \nearliest opportunity or the concept of immediate protection. The earliest opportunity would be \nbefore the mother deliver s. People’s situations may change. Someone might leave the country, \n50 \n \n    \n   \n   \n       \n \n \n      \n    \n  \n    \n     \n  \n    \n  \n    \n      \n      \n \n \n     \n    \n      \n   \n   \n  \n \n       \n     \n   \n       \n     \n      \n      \n   \n \n       \n    \n \n     \n  \n \n \n \n    \n       \n   \n   \n  \n    \n    \n   their insurance status may change, t heir perspective on protection of a child from RSV may \nchange, et cetera. It is very important to get them vaccinated as soon as possible. \nNotwithstanding Dr. Loehr ’s statement that nirsevimab seems to be a more efficacious and cost -\neffective , it is excell ent to have this option of the vaccine for the pregnant person prior to the \nbirth of the child. \nMs. McNally said she struggled with this recommendation for the reason that she does not know \nwhat the counseling looks like for the mother who asks her obstetrician if she should get this \nvaccine and the mother who ask s the child’ s pediatrician what she should do. Because of that, \nshe agreed with Dr. Lee that the stakeholder medical associations could get together and \nprepare a statement about this issue. She thought that would be immensely helpful for the \nconsumer. She also observed that it seemed like the ACIP had discussed shared clinical \ndecision- making recommendations a lot more lately. That gives her a certain level of discomfort \nas a consumer because while she believes there is a place for shared clinical decision- making, \nit makes her n ervous that there could be some baseline assumptions about the knowledge that \nconsumers have for risk of disease. She wondered whether there is a way to talk about best \npractices to revisit the idea of shared clinical decision- making in order to help ACIP arrive at \nbetter decisions of the future regarding vaccine recommendations. \nDr. Talbot reiterated how important it is that medical societies work on this process. The \npneumococcal vaccines have been complicated for years and had to be written out of the \ninfectious disease boards because they were too complicated. She worries that this has created \nanother very complicated recommendation. W hat happened with pneumococcus was low \nimmunization rates. She implored every society to talk. There needs to be massive education \nand it has to be better than what was done for pneumococcus. Dr. Kotton said that while she appreciated how complicated the decision- making was through all \nof this, she was excited to see that they were at a time in which there is a shared clinical \ndecision- making recommendation for adults ≥60 years of age, an RSV vaccine for pregnant \npeople, and monoclonal antibodies for infants. This is a horrible disease for many, especially \nimmunocompromised persons. She is cautiously optimistic that there will be diminished rates of \ndisease in multiple communities that hopefully will result in decreased transmissions to \nvulnerable populations. This is an exciting time in the medical world, and she is excited to see \nwhat things will look like with multiple protective vaccines for many different populations. Dr. Long said that she was outrageously grateful for the ACIP to think this through again with \nthe WG . She could not add up all of the hours that they have struggled with this. She \nappreciated everyone’s comments and thought this was the right decision to make. They w ill \nsee, through what may be a very messy year, whether one rises to a preference over the other \nand hopefully that both will become less expensive. \nDiscussion Points: Liaisons \nPatsy Stinchfield (NAPNAP) commented that during the 20 years she has been participating in \nthe ACIP, this has got to be one of the more complex decisions that has been before this \ncommittee . As a member of the RSV WG, she acknowledged the phenomenal work they did . \nThere were intense deliberations during the WG meetings, and the presentations and \nconversation during the meeting were very good in terms of highlighting the difference of \nopinion and complexities. Having listened to so many of these conversations over the years , \nshe agreed that this is complex and challenging. However, it was one of those times when they \nneeded to focus on the policy questions before them . Is it safe? Is it effective? Is it feasible? \n51 \n \n     \n       \n       \n     \n   \n  \n     \n     \n     \n    \n    \n    \n \n  \n \n \n \n    \n \n  \n      \n      \n     \n   \n   \n  \n \n \n \n \n \n \n  \n \n \n \n\n\n\n\n\n\n \n  \n  \n \n \n \n \n  \n  \n \n    \n   \n    \n        \n     \n    \n    \n  \n     \n   \n \n   They did not get to ask whether it is easy, but they know it is not going to be easy? What will \nhappen is that practice will follow ACIP policy , and the committee will re-review , discuss, and \nmeasure in the future. The practice barriers are what they need to be working on at this time. \nThe clinician is the linchpin and is the one who is going to be discussing the options  available. \nThey will need to be prepared for their own educational needs, attending the Clinician Outreach \nand Communication Activity (COCA) calls, listening to National Foundation for Infectious \nDiseases (NFID ) webinars, and making sure they are prepa red to share this with families. She \nvery much agreed with Dr. Lee’s observation about the quality improvements and that they \ncannot wait until they have all of the technical , financial , and other reimbursements in place \nwhen they have a very good product before them . They must make sure that they are \ncommunicating with their peers and parents alike, taking the barriers into consideration but not \nletting the barrier s stop them from advancing a very good product. \nADULT AND PEDIATRIC IMMUNI ZATION SCHEDULE ADDENDUM \nPresentation \nSarah Schillie, MD, MPH, MBA, CAPT USPHS discussed the addition of an addendum to the \nimmunization schedules . As a reminder, the immunization schedules are published on an \nannual basis, typically every February.57 There are two separate schedules , the Child and \nAdolescent Immunization S chedule that covers birth through 18 years of age and the Adult \nImmunization S chedule that covers ≥19 years of age. There are multiple sections in each of \nthese schedules that summarize the approved ACIP policy, including the Cover Page, Tables \nthat contain graphic rows of recommendations, Notes, and an A ppendix. The schedules are \npublished in 3 formats: PDF, webpage, and app. The 9 professional organizations listed here \npartner with CDC to approve the schedules, and some of these professional organizations \npublish the schedules : \nAmerican College of Physicians ( www.acponline.org ) \nAmerican Academy of Family Physicians ( www.aafp.org ) \nAmerican College of Obstetricians and Gynecologists ( www.acog.org ) \nAmerican College of Nurse- Midwives ( www.midwife.org ) \nAmerican Academy of Physician Associates ( www.aapa.org ) \nAmerican Pharmacists Association ( www.pharmacist.com ) \nSociety for Healthcare Epidemiology of America ( www.shea -online.or g) \nAmerican Academy of Pediatrics ( www.aap.org ) \nNational Association of Pediatric Nurse Practitioners ( www.napnap.org ) \nTraditionally, the schedules are published in February each year, but the publication process \nstarts in October with the ACIP vote. In November and December, professional organizations \napprove the schedule. In December and January, the draft s are developed and cleared for the \nMMWR reports and Annals of Internal Medicine report for the adult schedule. In February, the \nschedules are published along with the accompanying MMWR Notice to Readers and Annals of \nInternal Medicine report. The timeliness of schedule publication has several important \nimplications. First, some insurers link vaccine reimbursement to the vaccine listed on the \nimmunization schedules. Second, the ability of certain HCP to administer immunizations also is \nrelated to the schedule. For example, some states link pharmacist s’ immunization authority to \nthe schedule. Third , HCP knowledge and practices are related to the immunization \n57 www.cdc.gov/vaccines/schedules/index.html \n52 \n \n        \n    \n \n     \n     \n  \n    \n     \n     \n \n   \n   \n   \n   \n   \n   \n   \n  \n    \n \n \n  \n    \n      \n   \n     \n \n  \n \n \n \n  recommendations.  For example, if a HCP is referring to a schedule that is several months old, \nthey may not be aware of the most recent ACIP recommendations. \nThe ACA addresses immunization coverage and is interpreted by CMS. According to the ACA, \ninsurers must provide coverage for and must not impose cost -sharing restrictions for \nimmunizations that have a routine recommendation and that are listed on the immunization \nschedules of the CDC. Of note, the AC A does not specify the layout of the immunization \nschedule. Legally, CDC has discretion regarding the design of the immunization schedules. The \nentire document constitutes the schedule, not just the graphic bars or the tables. \nCDC takes a 3-pronged approach to address schedule timeliness. The immediate strategy \nconsists of the addition of addenda to help bring the schedule up -to-date. The short -term \nstrategy involves publication of the entirety of the schedule shortly after the October ACIP vote. \nThe longer -term strategy is to consider sustainable approaches to ensure the schedules remain \ndynamic and responsive, and to engage partners in the planning process. Regarding the \naddition of the addenda to the 2023 immunization schedules, the addenda will contain ACIP \nrecommendations that occurred after the 2023 schedule was published. The plan was to \nrelease the 2023 immunization schedules with the addenda the week following this meeting. \nWith this addition, all ACIP recommendations will formally be part of the CDC Immunization \nSchedules. \nTo describe the changes related to adding the addenda to the schedules, a red bar will be added to the top of the cover page to refer users to the addendum. A fifth step, also referring \nusers to the addendum, will be added to the steps of to how to use the document. Any new \nvaccine recommendations will be added to the table on the cover sheet. Here is the addendum for the Adult Immunization Schedule,  which consists of 1 page and includes vaccines for which \nrecent recommendations have been made, a synopsis of those recommendations, and the \neffective date of the recommendation: \n53 \n \n       \n \n \n \n     \n     \n      \n   \n  \n \n \n \n    \n \n    \n \n   \n     \n  \n  \n   \n   \n          \n   \n    \n   \n   \n   The addendum for the Pediatric Schedule is similar. It also is also 1 page, and is depicted here : \nIn summary, the release of the 2023 Immunization Schedules with the Addenda is anticipated \nduring the week following this meeting. This will formally incorporate all ACIP recommendations \ninto the 2023 CDC Immunization Schedules. There are also plans for short -and long- term \nsustainable strategies to address schedule timeliness and will ensure partner engagement with \nthis process. \nLiaison Statements \nJason Goldman , MD, FACP (ACP) provided a statement on behalf of the ACP. The American \nCollege of Physicians, with over 160, 000 members and the largest single specialty medicine \norganization representing all internal medicine specialists, greatly appreciates the work of the \nCDC and the Advisory Committee on Immunization Practices, especially the willingness to work \nwith the vaccine schedule. The ACP understands the challenges of analyzing copious amounts \nof data to put forth the best evidence- based recommendations. However, there is a need for \ntimely updates to the vaccine schedule so that practicing physicians can have guidance in implementing those guidelines. Obviously, one of those challenges is the delay created between \napproval by the committee, sign- off by the CDC director, and final publication of the schedule. \nThe ACA allows insurance companies to have up to a year to cover these life- saving vaccines , \nbut many will start that year at final publication and not at approval by the commi ttee. It is \nimperative that the schedule be updated, approved, and published as quickly as possible to \navoid unnecessary delays in implementation. The ACP appreciates the willingness of the CDC \nto expedite this process. The lack of insurance coverage creates unnecessary barriers to \naccess to care and further exacerbates healthcare disparities as uninsured and underinsured \npatients will not have access to these vaccines. The ACP also strongly agrees with the need for \n54 \n \n     \n    \n   \n    \n  \n   \n \n \n \n     \n    \n    \n   \n    \n \n \n  \n     \n    \n   \n     \n    \n   \n   \n   \n    \n \n \n  \n    \n   \n   \n  \n    \n   \n   \n     \n    \n   \n  \n   \n    \n  \n     \n  \n   \n   \n    a Vaccine for Adults program to address those gaps in coverage so patients can get the \nvaccines they need. Finally, the ACP would ask the vaccine manufacturers to provide vaccines \nfairly and equitably without preferential distribution to large systems and non- physician entities \nso that the physicians can vaccinate patients in their offices in a timely manner. Specifically, the \ndelays in distribution of influenza vaccines this season to many physician offices has created \nhardships for patients and decreased access to care. Once again, the ACP is supportive of the \ngood work of the committee and look s forward to continued collaboration to advance health \nequity and access to life- saving vaccines. \nSean O'Leary, MD, MPH (AAP) provided a statement on behalf of the AAP. The immunization \ndelivery system is complex, with many interrelated parts that need to work together to ensure \nthat the nation’ s children can receive timely and equitable access to vaccines. This is \nparticularly true when new vaccines are recommended by the Advisory Committee on Immunization Practices. Once the ACIP makes a recommendation for a new vaccine and the \nCDC director signs off on the recommendation, this prompts a series of steps that are critical to ensuring smooth and equitable rollout. The publication of official CDC recommendations is an \nessential step in this process. As an example, consider the PCV20 vaccine, the pneumococcal \nconjugate vaccine, which was recommended by the ACIP during its June meeting. AAP \nmembers have recently reported that some VFC programs are providing only PCV20 and that \nsome vaccine- buying groups are directing people to use this vaccine over other pneumococcal \nvaccines. However, this is problematic because a lack of formal recommendations in an \nupdated immunization schedule or publication in MMWR is leading to payment denials for \nPCV20, as well as delays in TRICARE coverage for children in military families. Timely updates \nto the immunization schedule would provide pediatricians with an authoritative source for the \nlatest immunization recommendations, which is invaluable at the point -of-care to maximize \nevery opportunity to vaccinate. The American Academy of Pediatrics strongly supports the \nefforts of the CDC to update the immunization schedule on an as -needed and timely basis. \nJean- Venable “Kelly” Goode, PharmD, BCPS, FAPhA, FCCP (APhA) provided a statement \non behalf of the nation’ s 330,000 pharmacists for the American Pharmacist Association. APhA \nis pleased to provide supportive comments on the importance of timely updates to the vaccine \nschedules. APHA, representing the profession of pharmacy, is honored to be one of the \norganizations granted the opportunity to review and indicate support of the adult vaccine \nschedule. Over the past 20- plus years, pharmacists and their teams have protected the public \nfrom vaccine -preventable diseases by recommending and administering vaccines, most notably \nof late, administering well over half the COVID -19 vaccines during the pandemic. APhA \nrecommends updating the schedules as recommendations and clinical guidance are approved by ACIP. It is important for policy and patient access to vaccines. An example is the RSV \nvaccine. ACIP voted on the recommendations in June for the vaccine to be administered as \nsoon as vaccine becomes available and throughout the RSV season. However, currently, it will \nnot be on the vaccine schedule until February. States regulate vaccine administration by \npharmacists and pharmacy personnel. Several states require that vaccines must be on the \nCDC/ ACIP  recommended schedule for pharmac ists or pharmacy personnel administration. The \ngap means that many thousands of patients will not have access to the RSV vaccine until \nFebruary if the schedule updates are not accelerated. Given the number of patients who receive \ntheir vaccines from a pharmacy team member, especially those in rural and medically underserved areas, it is imperative that the vaccine schedules be updated as new vaccines \nbecome available and recommended by CDC ACIP. Therefore, AP hA strongly supports timely \nupdates to the vaccine schedule for newly recommended vaccines to facilitate access to \nvaccination by pharmacists and pharmacy team members , and that payers be strongly informed \n55 \n \n    \n  \n \n     \n   \n     \n \n   \n    \n   \n  \n  \n     \n   \n   \n \n \n     \n    \n  \n    \n  \n   \n    \n     \n   \n   \n    \n  \n \n  \n   \n   \n   \n   \n   \n   \n  \n \n     \n     \n   \n       \n   \n  \n    \n  \n \n \n  that they do not need to wait for publishing of the MMWR for the updated schedule to begin \ncoverage for the ACIP recommended vaccines. \nPamela Rockwell , DO (AAFP) provided a statement on behalf of the AAFP . Family physicians \nprovide care for people of all ages from birth through end of life, including care for those who \nare pregnant. AAFP feels strongly that timely updates to the vaccination schedules are \nextremely important to allow family physicians and other health care professionals determine \nwho is due for vaccination and quickly. Many of the newly updated recommendations are scattered throu ghout CDC web pages and not easily accessed. As we enter the fall respiratory \nseason, many family physicians have expressed disappointment that updates on several \nvaccines, including influenza, pneumococcal, RSV, and COVID -19, are not easily accessible on \nthe Harmonized Child, Adolescent, and Adult Vaccination 2023 schedule. It was encouraging to \nhear from Dr. Schillie about the addendum to be added to the immunization schedules next \nweek. To summarize, AAFP encourages continuous and additional timely updates to the \nschedules as new vaccine recommendations are added or amended, as these are essential to ensure continued prevention of disease and improve public health through vaccination. \nRobert H. Hopkins, Jr., MD (Medical Director, NFID) provided an update on behalf of the \nNational Foundation for Infectious Diseases. NFID thanked the ACIP for its ongoing work to \nensure the availability of safe and effective vaccines and monoclonal antibodies to help protect \nthe most vulnerable individuals from RS V, and f or the addition of the ACIP schedule and plans \nto continue to update these schedules in the future to avoid some of the challenges with reimbursement and coverage. RSV impacts individuals of all ages, including premature infants and infants younger than 6 months. Each year in the US, RSV is estimated to cause more than \n2 million outpatient visits ; 58,000 to 80,000 hospitalizations ; and 100 to 300 deaths among \nchildren under 5 years of age. While immunizing pregnant women will be a tremendous step \ntoward RSV pr evention, healthcare professionals will continue to need clear guidance and \neducation to inform their decisions with patients and parents about the use of vaccines in \npregnant women and/or nirsevimab in infants. NFID is committed to collaborating with CDC and \npartners in educating healthcare professionals and the public to help facilitate the effective use of these active and passive tools in RSV prevention. The low uptake among pregnant women of \nvaccines to prevent influenza and COVID -19 underscores the importance of building confidence \nin all recommended vaccines. As partners in protecting public health, we must focus on using all \navailable tools to prevent RSV and protect those most at risk. For 50 years, NFID has been \ndedicated to educating and engaging the public, communities, and healthcare professionals \nabout infectious diseases across the lifespan. NFID commends the tireless efforts of ACIP in \nguiding US immunization policy and stands ready to support the work of ACIP and CDC, which \nis instru mental in saving lives and protecting public health. \nPatsy Stinchfield RN, MS, CPNP (NAPNAP) provided a statement on behalf of NAPNAP, the \nNational Association of Pediatric Nurse Practitioners to add her v oice to so many of the other \nassociation colleagues to say how important the updated schedule is. It is our tool. It is an \noutline. It is not all of the details, but it is critical for us to practice. Also, the great work that we \nhave had with our RSV vaccines and products will make that schedule even more important. On \nbehalf of pediatrics, we all know that RSV, in that in the infant age group as well as the older \nage group, can be a devastating disease. Today is a very, very great day in the pre\n…[truncated]", "summary": "MEETING OF THE ADVISORY  COMMITTEE ON IMMUNIZATION  PRACTICES (ACIP)  SEPTEMBER 22 , 2023  MEETING SUMMARY  CONTENTS   FRIDAY: SEPTEMBER 22, 2023 .................................................................................................................. 2  WELCOME AND INTRODUCTIONS ........................................................................................................ 2  Call to Order/Roll Call…", "source_url": "https://www.cdc.gov/acip/meetings/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/minutes/summary-2023-09-22-508.pdf", "doc_date": "2023-09-22", "case": "acip", "sub_case": "minutes", "tags": ["acip", "cdc", "vaccines", "minutes"], "page_count": 70}
{"title": "agenda 2023 09 12 508", "content": "Final - Agenda \nMEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP) \nCenters for Disease Control and Prevention \nAtlanta, Georgia 30329 \nSeptember 12, 2023 \n10:00 \n10:15 Introduction \nCurrent landscape of SARS-CoV-2 lineages \nCOVID-19 epidemiology Post-COVID conditions COVID-19 vaccine effectiveness update Economic analysis of COVID-19 vaccination COVID-19 vaccine safety surveillance \n12:15 12:25 Mod\n erna 2023 - 2024 COVID-19 vaccine \nNovavax 2023 - 2024 COVID-19 vaccine  \nPfizer-BioNTech 2023 - 2024 COVID-19 vaccine \n1:10 \n1:20 \n3:10 \n3:15 \n3:35 \n3:40 4:00 \nAcronyms \nCDC Centers for Disease Control and Prevention \nCMS Centers for Medicare and Medicaid Services  \nCOVID-19 Coronavirus disease 2019 \nEtR Evidence to Recommendations Framework \nFD\nA Food and Drug Administration \nGRADE Grading of Recommendations Assessment, Development and Evaluation \nHRSA Health Resources and Services Administration \nIHS Indian Health Service \nNCHHSTP National Center for HIV, Hepatitis, STD and TB Prevention [of CDC/DDID] \nNCIRD National Center for Immunization & Respiratory Diseases [of CDC/DDID]  \nNCEZID National Center for Emerging and Zoonotic Diseases [of CDC/DDID] \nNIAID National Institute of Allergy and Infectious Diseases \nOIDP Office of Infectious Disease and HIV/AIDS Policy \nSARS-CoV-2 Severe Acute Respiratory Syndrome Coronavirus 2 \nWG Work Group \nWHO World Health Organization \nVaST COVID-19 Vaccine Safety Technical (VaST) Work Group \nVE Vaccine Effectiveness AGENDA ITEM \nWelcome and introductions \nBreak \nBreak \nEvidence to Recommendations \nOverview of COVID-19 vaccine implementation  \nBridge Access Program \nBrea\nk \nPublic comment \nBreak \nVote \nAdjourn PRESIDER/PRESENTER(s) \nDr. Grace Lee (ACIP Chair) Dr. Melinda Wharton (ACIP Executive Secretary, CDC) \nDr. Matt Daley (ACIP, WG Chair) Dr. Natalie Thornburg (CDC/NCIRD) Dr. Fiona Havers (CDC/NCIRD) Dr. Sharon Saydah (CDC/NCIRD) Dr. Ruth Link-Gelles (CDC/NCIRD) Dr. Lisa Prosser (University of Michigan) Dr. Nicola Klein (Kaiser Permanente Northern California) \nDr. Fran Priddy (Moderna) \nDr.\n Filip Dubovsky (Novavax) \nDr. Kayvon Modjarrad (Pfizer-BioNTech) \nDr. M\negan Wallace (CDC/NCIRD) \nDr. Georgina Peacock (CDC/NCIRD) Dr. Evelyn Twentyman (CDC/NCIRD) \nDr.\n Megan Wallace (CDC/NCIRD)", "summary": "Final - Agenda  MEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)  Centers for Disease Control and Prevention  Atlanta, Georgia 30329  September 12, 2023  10:00  10:15 Introduction  Current landscape of SARS-CoV-2 lineages  COVID-19 epidemiology Post-COVID conditions COVID-19 vaccine effectiveness update Economic analysis of COVID-19 vaccination COVID-19 vaccine safety surveillance  12:15 12:25 Mod  erna 2023 - 2024 COVID-19 vaccine  Novavax 2023 - 2024 COVID-19 vaccine  …", "source_url": "https://www.cdc.gov/acip/meetings/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/agendas/agenda-2023-09-12-508.pdf", "doc_date": "2023-09-12", "case": "acip", "sub_case": "agendas", "tags": ["acip", "cdc", "vaccines", "agendas"], "page_count": 1}
{"title": "agenda 2023 08 03 508", "content": "Final- August 2, 2023 \nMEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP) \nCenters for Disease Control and Prevention \nAtlanta, Georgia 30329 \nAugust 3, 2023 \nThursday, August 3, 2023 \nAGENDA ITEM \n11:00 Welcome and introductions PRESIDER/PRESENTER(s) \nDr. Grace Lee (ACIP Chair)                               Dr. Melinda Wharton (ACIP Executive  \nSecretary, CDC) \n11:15 Respiratory Syncytial Virus Vaccines - Maternal/Pediatric Introduction EtR summary for nirsevimab Nirsevimab implementation considerations Clinical considerations for nirsevimab Workgroup considerations / proposed recommendations Dr. Sarah Long (ACIP, WG Chair) Dr. Jefferson Jones (CDC/NCIRD) Dr. Georgina Peacock (CDC/NCIRD) Dr. Jefferson Jones (CDC/NCIRD) Dr. Jefferson Jones (CDC/NCIRD) \nDr. Jeanne Santoli (CDC/NCIRD) 1:25 Vaccines for Children Resolution \n1:40 Break \n1:55 Public comment \n2:15 VOTES 1st season vote 2nd season vote VFC VOTE \nDr. Jefferson Jones (CDC/NCIRD) Dr. Jefferson Jones (CDC/NCIRD) Dr. Jeanne Santoli (CDC/NCIRD) \n3:00 Adjourn \nAcronyms \nCDC Centers for Disease Control and Prevention \nCMS Centers for Medicare and Medicaid Services  \nCOVID-19 Coronavirus disease 2019 \nEtR Evidence to Recommendations Framework \nFDA Food and Drug Administration \nGRADE Grading of Recommendations Assessment, Development and Evaluation \nHRSA Health Resources and Services Administration \nIHS Indian Health Service \nNCHHSTP National Center for HIV, Hepatitis, STD and TB Prevention [of CDC/DDID]  \nNCIRD National Center for Immunization & Respiratory Diseases [of CDC/DDID]  \nNCEZID National Center for Emerging and Zoonotic Diseases [of CDC/DDID] \nNIAID National Institute of Allergy and Infectious Diseases \nOIDP Office of Infectious Disease and HIV/AIDS Policy \nSARS-CoV-2 Severe Acute Respiratory Syndrome Coronavirus 2 \nWG Work Group \nWHO World Health Organization \nVaST COVID-19 Vaccine Safety Technical (VaST) Work Group \nVE Vaccine Effectiveness", "summary": "Final- August 2, 2023  MEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)  Centers for Disease Control and Prevention  Atlanta, Georgia 30329  August 3, 2023  Thursday, August 3, 2023  AGENDA ITEM  11:00 Welcome and introductions PRESIDER/PRESENTER(s)  Dr. Grace Lee (ACIP Chair)                               Dr. Melinda Wharton (ACIP Executive   Secretary, CDC)  11:15 Respiratory Syncytial Virus Vaccines - Maternal/Pediatric Introduction EtR summary for nirsevimab Nirsevimab…", "source_url": "https://www.cdc.gov/acip/meetings/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/agendas/agenda-2023-08-03-508.pdf", "doc_date": "2023-08-03", "case": "acip", "sub_case": "agendas", "tags": ["acip", "cdc", "vaccines", "agendas"], "page_count": 1}
{"title": "summary 2023 08 03 508", "content": "MEETING OF THE ADVISORY \nCOMMITTEE ON IMMUNIZATION \nPRACTICES (ACIP) \nAUGUST 3, 2023 \nMEETING SUMMARY \nCONTENTS  \nTHURSDAY: AUGUST 3, 2023 .................................................................................................................... 2 \nWELCOME AND INTRODUCTIONS ...................................................................................... 2 \nCall to Order/Roll Call ......................................................................................................... 2 \nAnnouncements .................................................................................................................. 2 \nMATERNAL/PEDIATRIC RESPIRATORY SYNCYTIAL VIRUS (RSV) VACCINES ................ 4 \nSession Introduction ........................................................................................................... 4 \nEvidence to Recommendations (EtR) Framework: Nirsevimab Updates ............................. 5 \nNirsevimab Implementation Considerations .......................................................................13 \nProposed Clinical Consideration Updates for Nirsevimab ..................................................19 \nWG Considerations / Proposed Recommendations ...........................................................20 \nVaccines for Children Resolution .......................................................................................26 \nPUBLIC COMMENTS ............................................................................................................27 \nVOTES ..................................................................................................................................30 \nVote #1 RSV Maternal/ Pediatric Recommendations ..........................................................30 \nVote #2 RSV Maternal/Pediatric Recommendations ..........................................................30 \nVote #3: VFC Resolution: RSV Maternal/Pediatric .............................................................30 \nCERTIFICATION ......................................................................................................................................... 33 \nACIP MEMBERSHIP ROSTER .................................................................................................................. 34 \nACRONYMS USED IN THIS DOCUMENT ................................................................................................. 42 \n \n  \n \n  \n \n  \n \n        \n      \n \n    \n    \n \n \n \n      \n     \n \n   \n     \n \n  \n  \n    \n  \n   \n \n \n \n   \n  \n  \n   \n    \n    \n   \n  \n        \n   \n    \n     \n      \n \n \n     \n     \n   \n     \n  THURSDAY : AUGUST 3 , 2023  \nWELCOME AND INTRODUCTIONS \nCall to Order/Roll Call \nDr. Grace Lee (ACIP Chair) called to order and presided over the August 3, 2023 Advisory \nCommittee on Immunization Practices (ACIP ) meeting. Dr. Lee co nducted a roll call, which \nestablished that a quorum was present. A list of Members, Ex Officios , and Liaison \nRepresentatives is included in the appendixes at the end of this summary document. No \nconflict s of interest (COIs) were identified. \nAnnouncements \nDr. Melinda Wharton (ACIP Executive Secretary, CDC) noted that copies of the slides for the \nmeeting were available on the ACIP website and were made available through a ShareLink ™ \nfile for ACIP Voting, Ex O fficios , and Liaisons Members . The ACIP is, at its heart, a public body. \nEngagement with the public and transparency in all of its processes are vital to the committee’s \nwork. She indicated that there would be 1 oral public comment session during this meeting, \nwhich was scheduled for 1:55 PM Eastern Time ( ET). To create a fair and more efficient \nprocess, individuals interested in making an oral comment were asked to submit a request \nonline in advance of the meeting. Priority is given to these advance requests. If more people make requests than can be accommodated, a blind lottery is conducted to determine who the \nspeakers will be. Speakers selected in the lottery for this meeting were notified in advance of \nthe meeting. Members of the public also may submit written comments via \nhttps://www.regulations.gov using Docket Number ID CDC- 2023-00 63. Information on the \nwritten public comment process, including information on how to make a comment, can be \nfound on the ACIP website. \nAs noted in the ACIP Policies and Procedures manual, ACIP members agree to forgo \nparticipation in certain activities related to vaccines during their tenure on the committee. For \ncertain other interests that potentially enhance a member’s expertise while serving on the \ncommittee , CDC may issue limited COI waivers. Members who conduct vaccine clinical trials or \nserve on data safety monitoring board s (DSMB s) may present to the committee on matters \nrelated to those vaccines, but those members are prohibited from participating in committee \nvotes on issues related to those vaccines . Regarding other vaccines of the concerned company, \na member may participate in discussions with the provision that he/she abstains on all votes related to that company. ACIP members state any COIs at the beginning of each meeting. \nApplications and nominations are being accepted for candidates to fill upcoming vacancies on \nthe committee. Detailed instructions for submissions of names for potential candidates to serve \nas ACIP members are available on the ACIP website. The deadline for applications for ACIP \nmemb ership has been extended to September 1, 2023 for the 4-year term beginning in July \n2024. \nBy way of introduction to the topic of the day’s meeting, Dr. Wharton b riefly reviewed 2 different \nprocesses for immunization, passive and active. Passive immunization involves the transfer of \npreformed antibody produced externally to provide protection to the recipient. Diphtheria \nantitoxin is still manufactured in horses, but most products for passive immunization come from \nhuman immune globulins . Some antibody products are made in cell culture systems. These \n2 \n \n   \n   \n  \n    \n      \n  \n \n  \n     \n    \n     \n  \n    \n    \n   \n \n       \n   \n    \n     \n   \n    \n     \n \n \n     \n   \n     \n  \n \n \n  \n    \n \n   \n \n \n \n     \n      \n      \n     \n    \n   \n   \n    \n   \n    \n \n \n  antibodies can provide excellent protection, but that protection wanes over time because the \nantibodies that are given only last so long. Transfer of maternal antibody across the placenta \nthat provides protection in early infancy is another example of passive immunization. In contrast, active immunization that occurs with traditional vaccines comes from the response of the \nrecipient ’s own immune system. Immu nological memory provides prolonged protection than \noccurs with passive immunization and can be lifelong. \nAdvances in biotechnology offer the opportunity to prevent infectious diseases with long -acting \nmonoclonal antibodies (mAbs)\n1 beyond what can be provided by traditional vaccines . When \nused for passive immunization, these products can provide a level of protection similar to what \nis observed with traditional vaccines, but for a limited period of time. They can be especially \nvaluable when full protection is needed without delay and when a traditional vaccine is not \navailable. For some indications, the protection provided by a long- acting monoclonal might be \n“long enough” to provide protection during the risk period with a single dose for the duration of a \nrespiratory disease season, for a critical part of a pregnancy, or for the duration of travel. \nCDC will prioritize for ACIP consideration of those long- acting mAbs for prevention of infectious \ndiseases that are: 1) expected to address conditions that result in a significant burden of \ndisease to the public's health; 2) are not expected, based on the characteristics of the product \nitself, to present significant implementation issues for immunization providers (e.g., mode of \nadministration, storage and handling, and frequency of administration); and 3) are expected to \nbe priced at a level allowing for incorporation into immunization programs. She returned the floor to Dr. Lee who called upon Dr. John Farley to provide an overview from the Food and Drug Administration (FDA). \nJohn Farley, MD, MPH (Director, CD ER/FDA) provided a few opening remarks on behalf of \nthe FDA. He reported that the FDA approved Biologics License Application ( BLA)- 761328 on \nJuly 17, 2023 that licensed nirsevimab -alip injection with the trade name Beyfortus ™. The \nindication was based on the data from adequate and well -controlled trials contained within the \nBLA and reads as follows : \nBEYFORTUS is a respiratory syncytial virus (RSV) F protein -directed fusion inhibitor \nindicated for the prevention of RSV lower respiratory tract disease in: \n• Neonates and infants born during or entering their first RSV season. \n• Children up to 24 months of age who remain vulnerable to severe RSV disease \nthrough their second RSV season. \nThe safety and efficacy of nirsevimab were supported by 3 clinical trials, Trials 03, 04, and 05. \nThe primary measure of efficacy was the incidence of medically -attended RSV lower respiratory \ntract infection (MA-RSV LRTI ). It was evaluated during the 150 days after nirsevimab \nadministration. MA- RSV LRTI, the endpoint, included all healthcare provider (HCP) visits (e.g., \nphysician office, urgent care, emergency room visits ) and hospitalizations for LRTD disease with \nworsening clinical severity and a positive RSV test. Trial 03 included 1,453 preterm infants born at ≥29 weeks of gestational age up to <35 weeks of gestation who were born during or entering \ntheir first RSV season. Of the preterm infants enrolled in the trial, 969 were randomized to a \nsingle dose of nirsevimab and 484 were randomized to placebo. Nirsevimab reduced the risk of \nMA-RSV LRTI by approximately 70% relative to placebo. The primary analysis group in Trial 04 \n1 https://www.who.int/images/default- source/departments/immunization- ivb/pdvac/who- monoclonal -\nantibodies.jpg?sfvrsn=f0870999_3 \n3 \n \n       \n  \n      \n   \n   \n      \n    \n     \n   \n  \n \n \n   \n   \n  \n   \n    \n    \n   \n    \n  \n   \n   \n  \n    \n    \n \n   \n \n \n \n   \n   \n   \n     \n    \n     \n \n \n     \n   \n    \n \n   \n   \n   \n \n     \n    \n included 1,490 term and late preterm infants born at ≥35 weeks gestational age of whom 994 \nwere randomized to a single dose of nirsevimab and 496 were randomized to placebo. \nNirsevimab reduced the risk of MA -RSV LRTI by approximately 75% relative to placebo in that \ntrial. Trial 05 was randomized, double- blind placebo- controlled multi- center trial in infants at high \nrisk for severe RSV disease. The trial enrolled 925 preterm infants as well as infants with \nchronic lung disease (CLD) of prematurity or congenital heart disease (CHD) . These patients \nwere randomized 2:1 to receive n irsevimab or palivizumab by intramuscular ( IM) injection. The \nefficacy of nirsevimab for prevention of MA -RSV LRTI in these high- risk patients during RSV \nseasons 1 and 2 was extrapolated from efficacy in Trials 03 and 04 , with demonstration of \ncomparable serum nirsevimab exposures between the high- risk population in Trial 05 and the \nTrials 03 and 04 populations. \nFDA imposed 2 post-marketing requirements. One focused on monitoring the prevalence of \nRSV variants , including the frequency of known n irsevimab resistance- associated substitutions \nand the second requirement to phenotypically assess certain RSV- A and RSV -B substitutions. \nThe sponsor has agreed to a number of post -marketing commitments. These include \nconducting the Harmony Study Extension that will evaluate antibody -dependent enhancement \nof RSV disease, and conducting an observational US -based long- term study of infants eligible \nto receive nirsevimab in their first year of life to assess the impact of RSV disease through Day \n511 post -dosing. The FDA has determined that a pharmacovigilance strategy is necessary to \nsupport coordinated monitoring and assessment of safety information from data sources across \nboth FDA and CDC. ACIP recommendations will be factored into the final pharmacovigilance \nstrategy as appropriate. The full details of this strategy will be finalized in a separate document \nwithin 90 days of marketing approval, and this pharmacovigilance strategy may be modified as \nsafety information accumulates during the post-marketing period. Dr. Farley noted that FDA \nReview Team members joined the meeting and were available to answer questions. \nMATERNAL/PEDIATRIC RESPIRATORY SYNCYTIAL VIRUS (RSV) VACCINES \nSession Introduction \nSarah S. Long, MD (Chai r, Maternal/Pediatric RSV WG) reminded everyone that p revious \nMaternal/ Pediatric RSV WG presentations to the ACIP focused on nirsevimab, the long- acting \nmonoclonal antibody against RSV ; the epidemiology and burden of RSV in infants ; the virology \nand immunology of RSV; the safety and efficacy of nirsevimab ; the cost effectiveness analysis \nfrom a CDC model and a comparison with a manufacturer model; the Evidence to \nRecommendation (EtR) Framework findings for nirsevimab ; and clinical considerations for \nnirsevimab. \nDr. Long indicated that the sole focus of the presentations for this session would be on \nnirsevimab because on June 8, 2023, the FDA Antimicrobial Drug Advisory Committee \n(AMDAC) evaluated and voted on 2 questions : \n1. Is the overall benefit -risk assessment favorable for the use of nirsevimab for the \nprevention of RSV lower respiratory disease in neonates and infants born during or entering their first RSV season? \n2. Is the overall benefit -risk assessment favorable for the use of nirsevimab for the \nprevention of RSV lower respiratory tract disease in children up to 24 months of age who remain vulnerable to severe RSV disease through their second RSV season? \n4 \n \n    \n  \n    \n   \n    \n  \n \n \n  \n   \n     \n     \n   \n \n \n    \n     \n \n  \n  \n \n \n  \n \n      \n     \n    \n \n  \n            \n \n  \n  \n \n   \n  \n \n  \n    \n    \n  \n \n      \n    \n \n  \n \n   The AMDAC voted 21 -0 in favor of the first question and 19 -2 in favor of the second question. \nMany committee members recognized the need for guideline groups such as the American \nAcademy of Pediatrics ( AAP) and ACIP to provide additional recommendations on the use of \nnirsevimab . As Dr. Farley noted earlier, the FDA approved nirsevimab on July 17, 2023 for the \nprevention of RSV LRTD in neonates and infants born during or entering their first RSV season \nand in children who remain vulnerable to severe RSV disease through their second RSV \nseason. \nThe agenda for this ACIP session included updated EtR Framework findings for nirsevimab, \nnirsevimab implementation considerations, clinical considerations for nirsevimab, \nMaternal/Pediatric RSV WG considerations and proposed recommendations and voting \nlanguage, and a Vaccines for Children (VFC) Resolution. Dr. Long concluded with the following \nproposed ACIP voting language so that members could be thinking about it throughout the \npresentations: \nInfants aged <8 months born during or entering their first RSV season are recommended \nto receive one dose of nirsevimab (50 mg for infants <5 kg and 100 mg for infants ≥5 kg) \nChildren aged 8– 19 months who are at increased risk of severe RSV disease and \nentering their second RSV season are recommended to receive one dose of nirse vimab \n(200 mg) \nEvidence to Recommendations (EtR) Framework: Nirsevimab Updates \nJefferson Jones, MD, MPH , FAAP, CDR, USPHS (CDC/NCIRD Co -lead, Maternal/Pediatric\nRSV WG ) reiterated that the following 2 policy questions were considered by the Maternal / \nPediatric WG regarding nirsevimab: \n1. Should one dose of nirsevimab be recommended for infants aged <8 months born during or \nentering their first RSV season (50 mg for infants <5 kg and 100 mg for infants ≥5 kg)? \n2. Should one dose of nirsevimab be recommended for children aged 8– 19 months who are at \nincreased risk of severe RSV disease and entering their second RSV season (200 mg)? \nThe rationale for inclusion of these age groups was that given an average RSV season of 4– 5 \nmonths, infants aged 8 months and children aged 20 months would be experiencing their \nsecond and third RSV seasons, respectively. \nAs mentioned earlier, nirsevimab is a form of passive immunization against RSV . While it may \nbe referred to as “ immunization” during the presentations and discussion, it is passive \nimmunization. Nirsevimab does not provide active immunity. Active immunity results from \ninfection or vaccination, which triggers an immune response . Passive immunity is when a \nperson receives antibodies from an external source. Examples include antibodies transferred \nfrom mother to baby through the placenta or breastmilk or direct administration of antibodies, \nsuch as i ntravenous immunoglobulin (IVIG) therapy or monoclonal antibodies such as \nnirsevimab.2 \n2 https://www.cdc.gov/vaccines/vac -gen/immunity -types.htm \n5 \n \n      \n   \n    \n       \n \n   \n \n  \n  \n    \n  \n \n    \n    \n    \n   \n   \n  \n    \n  \n   \n \n \n     \n    \n    \n     \n      \n  \n \n    \n   \n    \n    \n       \n     \n   \n   \n    \n  \n \n  \n  \n     \n \n   \n     \n    \n \n   \n \n  In terms of the PICO components for Policy Question #1 in this EtR analysis, the population \nincluded infants aged <8 months born during or entering their first RSV season. The intervention \nwas nirsevimab (1 injection prior to the start of RSV season or at birth if born during the season, \n50 mg if <5 kg or 100 mg if ≥5 kg) . The comparison was no nirsevimab prophylaxis. The \noutcomes included MA- RSV-associated LRTI , RSV-associated LRTI with hospitalization, RSV-\nassociated LRTI with intensive care unit ( ICU) admission , RSV-associated death , all-cause \nmedically attended LRTI , all-cause LRTI -associated hospitalization, and serious adverse events \n(SAEs). In terms of the EtR domains (e.g., Public Health Problem, Benefits and Harms, Values, \nAcceptability, Feasibility, Resource Use, and Equity), the domains of Benefits and Harms, \nFeasibility , and Resource Use included updates from what was presented during t he February \n2023 ACIP meeting . \nTo review the first domain of the Public Health Problem, data from the National Respiratory and \nEnteric Virus Surveillance System (NRE VSS)3, the primary source for monitoring RSV \nseasonality in the US, showed that there was very limited RSV circulation until late Spring 2021 \nthat was followed by a peak in activity in late Summer 2021 . Transmission continued throughout \nthe fall into December 2021. The most recent RSV season showed increasing RSV activity \nstartin g in late Summer 2022, with a peak in RSV transmission in October ─November 2022. To \nsummarize that, the 2022─ 2023 season began later than the 2021─ 2022 season but earlier \nthan pre- pandemic seasons. This suggests an incremental reversion to pre- pandemic \nseasonality  with winter peaks and highlight s the uncertainty in when the next RSV season will \nstart. \nIn terms of epidemiology, RSV is the most common cause of hospitalization in US infants. The \nhighest RSV hospitalization rates are in the first months of life. The risk declines by month with \nincreasing age in infancy and early childhood. While p rematurity and other chronic diseases \nincrease the risk of RSV -associated hospitalization, most hospitalizations are in healthy term \ninfants. The WG felt that RSV -associated disease in infants born during or entering their first \nRSV season is of public health importance. \nRegarding the Benefits and H arms domain, there have been no updates to the GRADE \n(Grading of Recommendation Assessment, Development and Evaluation) assessment of the \nevidence presented in February 2023. However, some additional data were received from \npooled estimates combining Phase 2b and Phase 3 clinical trials estimate comparing the \nnirsevimab arm to the placebo arm in addition to concerns in ter ms of the certainty of \nassessment. T he estimated efficacy was 79% for MA-RSV LRTI , 80.6% for hospitalization , and \n90% for ICU admission. No RSV -associated deaths were recorded, though this outcome could \nnot be evaluated. The estimated efficacy against all -cause medically attended LRTI was 34.8% \nand against all- cause LRTI hospitalization was 44.9%. The risk ratio comparing SAEs in infants \nreceiving nirsevimab versus receiving placebo was 0.73. \nIn summary of GRADE for nirsevimab, there is high certainty that Nirsevimab is effective in \npreventing medically attended RSV and RSV hospitalization. In addition to preventing all- cause \nmedically attended LRTI and LRTI hospitalization, there is moderate certainty that nirsevimab is \neffect ive in protecting against RSV LRTI with ICU admission and that SAEs are not more \ncommon in infants receiving nirsevimab compared with placebo. Additional safety data were \nprovided during the AMDAC meeting on nirsevimab4. The most commonly reported adverse \nreactions (ARs) were injection site reactions (0.3% ) and rash ( 0.9% ). The FDA noted an \n3 https://www.cdc.gov/mmwr/volumes/72/wr/mm7214a1.htm \n4 https://www.fda.gov/advisory- committees/advisory -committee- calendar/june-8- 2023- meeting- antimicrobial -drugs -advisory -\ncommittee- meeting- announcement -06082023 \n6 \n \n      \n  \n \n      \n     \n      \n   \n     \n   \n  \n  \n      \n  \n     \n   \n     \n  \n     \n   \n        \n  \n \n \n  \n     \n   \n       \n     \n   \n \n \n      \n     \n   \n     \n  \n       \n      \n    \n    \n    \n \n  \n \n     imbalance in deaths between n irsevimab and the control arms but determined that the deaths \nwere unlikely to be related to nirsevimab. \nThe sponsor shared data from the ongoing Phase 3b study known as HARMONIE .5 The \nHARMONIE study enrolled 8,058 infants. The age at enrollment was : 49% <3 months , 24% 3-5 \nmonths , and 28% ≥6 months . Of the infants, 85% were born at term and 50% were born during \nthe RSV season. This study is being conducted in France, the United Kingdom (UK), and \nGermany. While these results are from August 8, 2022–February 28, 2023 , the study is \nongoing. The participants were randomized to n irsevimab or no injection, meaning the control \ngroup was not given a placebo injection. The primary endpoint was RSV hospitalization, which \nwas a LRTI hospitalization with a positive RSV test. RSV tests were ordered by clinicians for patients with LRTI per the standard of care as opposed to systematically on all patients with \nLRTI hospitalizations . Participants will be followed for at least 12 months after randomization. At \nthe end of the RSV season, the preliminary efficacy results were released, which were \npresented during this session. These results were with a median post -randomization follow- up \ntime of 2.5 months. HARMONIE preliminary results reported an efficacy against RSV \nhospitalization of 83% , 76% against severe disease (e.g., oxygen saturation below 90% and \noxygen given), and 58% against all-cause hospita lization with LRTI during the RSV season. For \nsafety, Grade 1 AEs were reported to be slightly higher in the nirsevimab arm (29%) versus the \nno intervention arm (25%). The rate s of Grade 2 and Grade 3 AEs were similar between the \nnirsevimab and control arm s. It is important to note that these results have not been peer -\nreviewed or published in the scientific literature. \nTo summarize the Benefits and Harms domain, the overall GADE grade evidence rating was \nmoderate. The results were downgraded based on impr ecision for protection against ICU \nadmissions because of few recorded events and imprecision of SAEs because rare events are unlikely to be detected. The WG felt that the desirable anticipated effects of nirsevimab were \nmoderate to large, that the undesirable anticipated effects of nirsevimab were minimal to small, \nand that the desirable effects outweighed the undesirable effects and favored n irsevimab over \nno intervention. \nThe next domain is Values , for which no updates were available. In a survey of people currently \npregnant or pregnant within the last 12 months conducted by the CDC, the University of Iowa , \nand the Rand Corporation on RSV immunizations, only 33% of respondents thought their baby \n“definitely ” or “probably would” get an RSV infection within 1 year after being born. Despite \nbeing unsure or perceiving RSV risk to be low, respondents were worried that their baby would \nneed to be hospitalized if they got sick with RSV (mean response 4 of 5, with 5 being most \nworried ). Of the respondents , 70% said they “definitely ” or “probably would” get an RSV \nantibody injection for their baby if safe and effective. The WG determined that the target \npopulation probably feels that the desirable effects are large relative to undesirable effects . The \nWG varied in whether they felt there was important uncertainty about , or variability in , how much \npeople value the main outcomes. \n5 Study not peer- reviewed and information provided directly by sponsor; https://www.cl inicaltrials.gov/study/NCT05437510 \n7 \n \n      \n  \n    \n     \n       \n     \n \n \n   \n   \n \n    \n     \n      \n   \n   \n      \n      \n  \n      \n   \n     \n     \n  \n    \n   \n     \n \n \n      \n     \n  \n       \n      \n      \n     \n    \n     \n  \n \n \n  \n    \n  \n   \n  \n   \n     \n The next domain is Acceptability with key stakeholders, for which no updates were available. In \na survey of US pediatric providers, over 85% agreed that parents need more information about \nRSV, that immunization could help prevent RSV, and that immunization policy should ensure all \nchildren get access.6 The American Academy of Pediatrics ( AAP) and the National Foundation \nfor Infectious (NFID) Disease Roundtable have stated the need for safe and effective RSV \nprevention products.7 The WG felt that passive immunization with nirsevimab was or probably \nwas acceptable to key stakeholders. \nFeasibility domain considerations were reviewed in the next presentation by Dr. Georgina \nPeacock , but the WG felt that nirsevimab probably will be feasible to implement. \nThe R esource Use domain , the primary source of data was a cost -effectiveness analysis \nperformed by the University of Michigan. Since the cost- effectiveness analysis was presented to \nACIP in February 2023, the company provided an updated cost estimate of the product. The list \nprice was estimated to be $495 and the cost for the V FC program was estimated to be $395. \nAssuming nirsevi mab is administered as 50% under the VFC and 50% under private insurance, \nthe average price was $445. This price was not final at the time of this session per the WG’s \nunderstanding. Mortality assumptions were modified to include individuals at increased risk of \nsevere disease and savings from not using palivizumab to those recommended to receive it \nwere incorporated. Other inputs were unchanged from the previous model presented during the \nFebruary 23, 2023 ACIP meeting. The number needed to immunize with nirsevimab to prevent \n1 health outcome was 17 for an outpatient visit, 18 for an ED visit, 128 for inpatient, 581 for ICU \nadmission, 24 per inpatient day, and 194 per ICU day. The cost per health event averted was \n$2,662 per outpatient visit, $7,473 per ED visit, $19,909 per inpatient admission, $90,494 per \nICU admission, $3,687 per inpatient day, and $30,165 per ICU day. The updated base case \nresults of the cost -effectiveness analysis was $102,811 per quality adjusted life year saved. The \nWG felt that n irsevimab is or probably is a reasonable and efficient use of resources . A full \npresentation for this updated cost -effectiveness analysis was included in the extra slides. \nThe primary update to the Equity domain was that that if ACIP recommends use of nirsevimab, \nACIP also would vote on a VFC Resolution for nirsevimab. To summarize equity, national \nstudies of death certificates found higher rates among non- Hispanic Black children compared \nwith non- Hispanic White infants and children 1─4 years of age .8 ICU admission rates for RSV \namong non -Hispanic Black infants <6 months of age were 1.2 to 1.6 times higher than among \nnon-Hispanic White infants.9 RSV hospitalization rates were 4 to 10 times higher among Alaska \nNative and American Indian (AI/AN) children <24 months of age than the rate in the general \npopulation.10 Studies of RSV hospitalization by race and ethnicity have differing results.11 The \nWG felt that nirsevimab would increase health equity. \n6 https://admin.allianceforpatientaccess.org/wp- content/uploads/2023/01/AfPA -and-NCfIH_The -Indirect -Impact -of-RSV_Survey -\nReport_Jan- 2023.pdf \n7 AAP COID BGC Pediatrics 2014 Aug;134(2):415- 20; and https://www.nfid.org/wp -content/uploads/2022/04/NFID -RSV-Call-to-\nAction.pdf \n8 Hansen J Infect Dis 2022 Aug 15;226(Suppl 2):S255-S266 \n9 Unpublished data from RSV -NET, CDC \n10 Atwell Pediatrics 2023, e2022060435 \n11 Hall Pediatrics 2013 Aug;132(2):e341- 8; Hall NEJM 2009;360(6):588– 598; Iwane Pediatrics 2004 Jun;113(6):1758-64, findings \ndiffered by age group; and Rha Pediatrics 2020 Jul;146(1):e20193611, findings differed by age group \n8 \n \n       \n \n \n \n \n    \n  \n     \n \n \n  \n  \n    \n    \n   \n    \n \n       \n    \n  \n  \n  \n \n   \n \n  \n  \n   \n \n  \n \n \n     \n       \n Displayed in this table are the WG’s judgments of the EtR Framework analysis for the first RSV \nseason indication: \nThe WG felt that the desirable consequences clearly outweigh the undesirable consequences in \nmost settings , with a minority opinion that the desirable consequences probably outweigh the \nundesirable consequences. The WG recommended the intervention for all infants in their first \nRSV season. \nTo review the EtR analysis for the second RSV indication, the population is chi ldren aged 8– 19 \nmonths who are at increased risk of severe RSV disease and who are entering their second \nRSV season. The intervention was nirsevimab (200 mg [2 x 100 mg] injection near start of \nsecond RSV season) and the comparison was no nirsevimab prophylaxis. The outcomes were \nthe same as those used for the first indication. Domains with updates unique to the second \nseason included the P ublic Health Problem and Resource Use. \nFor the P ublic Health Problem, the WG previously presented that they felt the risk groups to \nreceive nirsevimab f or the second RSV season could be based on the AAP recommendation for \npalivizumab for a child’ s second RSV season.12 The WG assumed nirsevimab to be cost -saving \ncompared with palivizumab. The proposed recommendation to receive nirsevimab when \nentering thei r second RSV season would include the following groups: \nChildren with CLD of prematurity if they require medical support (chronic corticosteroi d\nt\nherapy, diuretic therapy, or supplemental oxygen) during the 6- month period before t he\ns\ntart of the second RSV seas on\nC\nhildren with severe immunocompromis e\nC\nhildren with cystic fibrosis if manifestations of severe lung disease (previous hospitalizati on\nf\nor pulmonary exacerbation in the first year of life or abnormalities on chest imaging tha t\nper\nsist when stable) or weight for length <10th percentil e\n12 American Academy of Pediatrics. Committee on Infectious Diseases [Respiratory Syncitial Virus.] In: Kimberlin DW, Barnett ED, \nLynfield R, Sawyer MH, eds. Red Book : 2021 Report of the Committee on Infectious Diseases. Itasca, IL: American Academy of \nPediatrics, 2021 \n9 \n \n    \n       \n     \n  \n     \n   \n      \n \n \n \n   \n   \n      \n    \n   \n   \n   \n      \n   \n \n  \n      \n     \n   \n     \n   \n   \n  \n \n \n  \n  \n    \n      \n   \n   \n     \n  \n \n        \n \n  \n      \n          \n \n       \n To evaluate the evidence if other risk groups should be considered for a recommendation, CDC \nconducted 2 analyses, a systematic review of the literature and an analysis of the M arket Scan \nnational claims database. The systematic review included any studies that compared RSV \nhospitalization rates among children with risk factors to a healthy control among children 6─ 24 \nmonths of age . Among 3,825 abstracts reviewed, 6 studies were identified. CLD, CHD, and \nneuromuscular  disease (NMD) were analyzed in these studies. These studies indicated an \nincreased risk of hospitalization for these risk factors. No studies evaluating other risk factors \nwere identified. \nGiven the limited evidence available in the systematic review, CDC conducted an analysis of the \nMarket Scan national claims database for select risk factors for severe RSV disease during the \nsecond RSV season using data from 2015─2021. Using International Classification of Diseases \n(ICD)- 9 and ICD-10 codes, children were identified with and without selected conditions (e.g., \nCLD, CHD, Down syndrome, NMD, pulmonary malformations, immunodeficiency, cystic fibrosis) \nand children who were hospitalized with RSV. The rates of RSV hospitalization among children \nwith a chronic condition were compared to children without any of these chronic conditions . \nIncreased rates of hospitalization were seen for all conditions. It is important to note that a \nprimary limitation in this study is that RSV testing may be more common for children with risk \nconditions , inflating RSV -specific hospitalization rates. \nSeveral prior studies have documented increased incidence of RSV hospitalizations among \nAI/AN children.13 One study found that rates of RSV hospitalization in AI/AN children were 4 to \n10 times the average rates of US children overall aged 12─ 23 months as determined from the \nNew Vaccine Surveillance Network (NVSN) .14 These studies have been conducted in specific \npopulations and may not be broadly representative of the risk in all AI/AN children. Findings of \nthese studies do not separate environmental, sociocultural, or other factors that may increase severe disease risk. And some AI/AN communities are also in remote areas that can make \ntransportati on of children with severe RSV to an appropriate health care setting more \nchallenging.\n15 \nTo summarize the Public Health Problem domain, the WG group felt that evidence for RSV \nburden among children 8 ─19 months entering their second RSV season with specific risk \nconditions is limited. The WG felt that n irsevimab should be recommended to the same groups \nthe AAP recommends for palivizumab for the second RSV season. The WG also felt that \nnirsevimab should be recommended to AN /AI children entering their second RSV season. In \naddition, the WG felt that RSV disease among children who are at high risk of severe disease16 \nin their second RSV season was of public health importance. \n13 Atwell 2023 Pediat rics 2023 Jul 14;e2022060435; Karron et al. J Infect Dis 1999; Holman et al. Pediatrics 2004; Lowther et al. J \nPed Infect Dis 2000 \n14 Atwell 2023 Pediatrics 2023 Jul 14;e2022060435 \n15 American Academy of Pediatrics. Committee on Infectious Diseases [Respirat ory Syncytial Virus.] In: Kimberlin DW, Barnett ED, \nLynfield R, Sawyer MH, eds. Red Book: 2021 Report of the Committee on Infectious Diseases. Itasca, IL: American Academy of \nPediatrics, 2021. \n16 For groups recommended to receive palivizumab in their second RSV season by the American Academy of Pediatrics and \nAmerican Indian and Alaska Native children \n10 \n \n     \n    \n  \n     \n   \n  \n     \n     \n      \n \n    \n     \n    \n    \n    \n      \n  \n \n    \n     \n       \n    \n   \n  \n  \n    \n    \n   \n  \n \n   \n    \n   \n   \n     \n   \n    \n   \n      \n     \n   \n \n  \n \n          \n     \n   Moving to the Benefits and Harms domain, a pharmacokinetic trial17 was conducted that \nrandomized children at risk of severe RSV disease to palivizumab or nirsevimab. In the second \nRSV season, 220 participants received n irsevimab and 42 received palivizumab. Among those \nwho received nirsevimab, 2 pharmacokinetic endpoints have been reported. The Day 150 \nnirsevimab concentration s compared with the Phase 3 Prevention of Medically Attended Lower \nRespiratory Tract Infection Due to Respiratory Syncytial Virus in Healthy Late Preterm and Term \nInfants (MELODY) efficacy trial among late preterm and term infants that showed efficacy. The \nproportion of participants who had an area under the curve (AUC) nirsevimab concentration \nabove a target based on the efficacy trial data in term and preterm infants of 12.8 mg day/ml. \nAmong recipients of nirsevimab, Day 150 concentrations were higher in the high- risk infants \nwho received 200 mg in the second RSV season (Trial 05 ) that infants who received 50 mg (if \n<5kg) or 100 mg (if >5kg) in P hase 3 MELODY trial ( Trial 04) . For the other pharmacokinetic \nendpoint among recipients of nirsevimab in the second RSV season, most had an AUC \nnirsevimab concentration above the target threshold. Among infants with CLD and CHD, 97.7% \nand 100% respectively had concentrations above that target threshold. For safety, no AEs were \njudged to be related to nirsevimab or palivizumab in the second RSV season follow -up period.18 \nIn summary of GRADE for the second RSV season, nirsevimab may be effective in preventing \nMA-RSV LRTI, but with low cert ainty. The prevalence of SAEs was not significantly different in \nthe intervention group or control group, but the certainty of evidence was very low. No data were \navailable for other outcomes. Overall, the evidence rating was very low certainty (Type 4). T his \nwas downgraded on indirectness because of the use of pharmacokinetic data as a surrogate for \nefficacy , the population did not include children who match the proposed indication outside of \nCLD and CHD, the study was small in size, and no placebo group was included for a comparison. For groups recommended to receive palivizumab in their second RSV season by \nthe AAP and AI /AN children, the WG felt that the desirable anticipated effects were moderate, \nthe undesirable anticipated effects were minimal, and the desirable effects outweighed the undesirable effects and favored n irsevimab over no intervention. \nNo additional data were available for the domains of Values or Acceptability specific to high- risk \npopulations in their second RSV season. The WG determined that for groups recommended to \nreceive palivizumab in their second RSV season by the AAP and AI /AN children, the target \npopulation probably feels that the desirable effects are large relative to undesirable eff ects. The \nWG also felt that there probably was not important uncertainty or variability in how much people \nvalued the main outcomes. The WG felt that prevention with nirsevimab was, or probably was, \nacceptable to the key stakeholders. For feasibility, an additional visit to a provider might be \nneeded for administration of nirsevimab prior to the beginning of the second RSV season. The \nWG felt that n irsevimab was probably feasible to implement among children 8─ 19 months of \nage at increased risk of severe RSV disease entering their second RSV season for groups \nrecommended to receive palivizumab in their second RSV season by the AAP and AI/AN \nchildren. \n17 Domachowske J, Madhi SA, Simões EAF, Atanasova V, Cabañas F, Furuno K, et al. Safety of nirsevimab for RSV in infants with \nheart or lung disease or prematurity. New England Journal of Medicine. 2023;386(9): 892–894. doi:10.1056/NEJMc2112186 \n18 Source: FDA briefing document for Antimicrobial Drugs Advisory Committee June 8, 2023 meeting \n11 \n \n   \n    \n     \n    \n      \n      \n     \n   \n    \n    \n   \n    \n   \n  \n  \n \n \n \n   \n    \n    \n    \n \n \n      \n  \n \n   \n     \n  \n  \n \n    For the Resource Use domain, the inputs were updated similar to the cost -effectiveness \nanalysis for the first RSV season indication. As presented in February 2023, theoretical groups \nof children with increased risk were created with 2, 4, 6, and 10 times higher risk than the \ngeneral population 8─ 19 months as of October for beginning of RSV season. Compared w ith \nFebruary, 2 scenarios were created to account for th e uncertainty in mortality in this group. As \npreviously presented, the incidence of RSV -associated hospitalization and incidence per \nhospitalization were increased. For the other scenario, the incidence of RSV -associated \nhospitalization was increased. However, the mortality per hospitalization was not changed \nbecause of lack of evidence. No increases were made to the incidence of outpatient and ED \nvisits, healthcare costs, or quality adjusted life year s (QALY) lost with RSV disease for these \nincreased risk groups due to lack of data.19 The cost was updated to $890 for nirsevimab per \nchild based on 2 times the $445 per dose assumed in the first season analysis to account \nfor the 200 mg injections needed. Baseline mortality estimates were modified to include high-\nrisk individuals and other inputs were unchanged similar to the first season model. This table \ndisplays the updated results : \nThe WG felt that nirsevimab use among children 8─ 19 months of age entering their second \nRSV season who are at increased risk of severe disease is probably a reasonable and efficient \nallocation of resources. Like all domains, this assumes increased risk of severe disease refers \nto groups recommended to receive palivizumab in their second RSV season by the AAP and \nalso including AI /AN children. \nFor the E quity domain, no updated information is available. As previously presented, equity \nissues differ by chronic condition among infants and young children. AI/AN children have \nreported higher hospitalization incidence rates than the general population during their second RSV season. Non-Hispanic Black and Hispanic populations have higher reported rates of \npreterm birth than non -Hispanic White populations. The WG felt that n irsevimab use probably \nwould increase health equity. \n19 Same assumption as previous model presented at February 23, 2023 ACIP meet ing \n12 \n \n        \n   \n \n \n \n  \n    \n   \n   \n   \n  \n \n  \n \n     \n \n   \n   \n    \n    \n \n  \n     \n      \n     \n   \n   \n      \n    \n    \n \n   \n \n  Displayed in this table are the WG’s judgments of the EtR Framework analysis for children at \nhigh risk entering their second RSV season : \nAfter reviewing the totality of the data presented during this session and acknowledging \nuncertainties around the aspects of the data, the WG felt that the desirable consequences \nprobably outweigh the undesirable consequences in most settings, with a minor ity opinion that \ndesirable consequences clearly outweigh the undesirable consequences. The WG proposed to ACIP to recommend the intervention for groups recommended to receive palivizumab in their \nsecond RSV season by the AAP and for AI/AN children. \nNirse vimab Implementation Considerations \nGeorgina Peacock, MD, MPH, FAAP (CDC/NCIRD) briefly reviewed some of the many \nimplementation considerations related to nirsevimab , such as the definition of “vaccine,” c ost, \nstorage and handling, h ospital dosing, o utpatient dosing, c oding and Immunization Information \nSystems (IISs), timing of vaccination, second y ear vaccinations , vaccine administration , safety \nreporting, and v accine confidence and demand . There are some mitigation strategies and CDC \nis exploring ot hers internally and with its partners in the field. \nOne issue that has arisen is the definition of “vaccine. ” There is no statutory definition of \n“vaccine” in the statute for the VFC program (section 1928 of the Social Security Act) .\n20 There \nalso is no st atutory definition of “vaccine” in the Affordable Care Act (ACA) (section 2713 of PHS \nAct),21 or its implementing regulations, which has a provision that mandates coverage of \nvaccine recommendations included on CDC ’’s immunization schedules. Therefore, CDC has \ndetermined that nirsevimab is eligible for inclusion in the Childhood Immunization Schedule and \nthe VFC. It is important to note that some states do have different definitions of “vaccine ” in their \nstate statutes , which may affect the state purchase of vaccine in universal purchase states. \nHowever, it does not affect the use of federally purchased vaccine in states. \n20 https://www.ssa.gov/OP_Home/ssact/title19/1928.htm \n21 https://www.federalregister.gov/documents/2015/07/14/2015- 17076/coverage- of-certain- preventive- services- under- the-affordable-\ncare-act \n13 \n \n  \n        \n    \n   \n    \n   \n  \n  \n \n \n  \n      \n     \n       \n    \n        \n  \n \n    \n \n \n    \n   \n      \n \n \n  \n   \n       \n   \n      \n      \n  \n    \n  \n  \n      \n   \n    \n    \n     \n   \n \n    \n   \n  \n   \n  \n   \n \n   Nirsevimab is a costly product. If nirsevimab is recommended by ACIP, it will be covered by \ninsurance and included in the VFC program. It is important to make sure that there is equitable \naccess to nirsevimab . The cost of n irsevimab is a potential implementation barrier, particularly \nfor outpatient settings or ambulatory practices. In the provider agreement for VFC providers , \nthere is a provision that if a practice has both public and private payers, they must carry stock . \nRecognizing that this may be challenging for some practices , CDC is working through some \npotential short -term solutions that could be implemented during the ramp -up of inclusion of \nnirsevimab in the VFC program. \nThis product is similar to other routine vaccines for children in terms of storage, handling, and \nadministration. Nirsevimab is administered as an intramuscular (IM) injection using a single -\ndose pr e-filled syringe and can be administered simultaneously with other childhood vaccines. \nDosing is weight -based (50 mg if <5 kg; 100 mg if ≥5 kg; 200 mg (2x100 mg) for high- risk \nchildren entering second RSV season). S torage and handling are similar to other routine \nvaccines. Nirsevimab is stored in a refrigerator at 2-80 C and may be kept at room temperature \n(20-250 C) for up to 8 hours . \nThere have been some questions about scope of practice issues . Different jurisdictions or states \nmay have different scope of practice statutes related to who can administer injectable therapeutics versus vaccines. CDC conducted a scan of different state statutes or laws to \ndetermine who is allowed to administer therapeutics. It appears that in most states, medical \nassistants who frequently do administer vaccines also will be able to deliver injection drugs. \nWhile there is some variability, this does not appear to be major issue related to scope of \npractice. \nThere have been conversations about where doses will be given and the age of the infant . \nApproximately 10% of birthing hospitals participate in the VFC program. There has been a \nsuggestion that if nirsevimab were to be given in the hospital, this would be s imilar to what is \ndone with hepatitis B vaccine. Hepatitis B vaccine is bundled into a payment model for newborn \ncare. It is important to note that hepatitis B vaccine costs approximately $13 to $16 a dose.\n22 If \nnirsevimab were to be included in a bundled payment model, it may take time for that to be put \ninto practice. Regardless of where the dose is given, it is critical to ensure that documentation of \nnirsevimab administration and all parties involved are sent to the primary care provider (PCP). \nThere are some potential challenges with n irsevi mab being entered into IISs since it is a \ntherapeutic versus a vaccine. Comprehensive maternal- neonatal records will become even \nmore critical if maternal RSV vaccine is licensed and recommended and will adds to the need \nfor communication between maternal records, hospital records, and ambulatory settings or \nprimary care offices. Regarding outpatient administration, communication from the birthing \nhospital is extremely important related to this product. CDC also recognize s that an initial \ninvestment by pedi atricians who are unsure on the demand for this product may create some \nchallenges . Historically, there has been a lag in insurance payment s for new products. \nBecause of the uniqueness of this product, there is a n eed to consider different coding \nrequirem ents. The initial meeting and American Medical Association ( AMA ) decision pertaining \nto Current Procedural Terminology (CPT) codes classified n irsevimab as a drug or a \ntherapeutic. That means that currently, it is associated with an administration code that does not \ninclude a counseling component and is not eligible for a standalone counseling component. \nCDC understands that there are efforts underway potentially to propose a unique code for thi s \n22 https://www.cdc.gov/vaccines/programs/vfc/awardees/vaccine- management/price- list/index.html \n14 \n \n     \n \n \n   \n    \n  \n \n \n \n \n  \n    \n    \n     \n  \n     \n  \n \n    \n  \n    \n    \n  \n   \n \n    \n     \n  \n    \n \n \n    \n   \n    \n     \n    product that would include counseling and storage and handling components. Again, there may \nbe potential challenges in recording the doses in IISs. \nThis graphic depicts the complexity of the steps involved in paring systems for administering a \nnewly authorized vaccine across the US , which illustrates that there are numerous processes \nand partners involved and that it takes time: \nTo further detail IISs and vaccine forecasting considerations, coding of nirsevimab as a \ntherapeutic instead of a vaccine could create challenges with internal provider ordering, \nprovision of a vaccine record, and interoperability and data exchange with electronic health \nrecords (EHRs) and IISs. In addition, there are some forecasting issues related to Clinical \nDecision Support (CDS) systems for immunizations. The dosage is determined by weight , but \nCDS systems do not have access to patient weight. This could create challenges with \nforecasting doses. Second season recommendations also may be challenging. In addition, CDS \nsystems are unable to take into account maternal vaccination history for forecasting of infant \nnirsevimab immunization. \nSpecial considerations also add complexity. Timing of vaccination is based on RSV season. \nTropical climates may have different or unpredictable seasonality when compared with most of \nthe continental US (CONUS) . There also is variability in different localities. For example, \nseasonality in Alaska is less predictable and of longer duration. For those who are going to \nreceive a second dose, high- risk populations must be defined and palivizumab \nrecommendations must be clarified in the setting of nirsevimab availability. \nReporting of AEs is more complicated for nirsevimab than other immunizations being classified \nas a therapeutic versus a vaccine. If nirsevimab is administered alone , suspected AEs are \nreported to MedWatch. If nirsevimab is administered simultaneously with any vaccine, \nsuspected AEs are reported to the Vaccine Adverse Event Reporting System (VAERS) and \nadditional reporting to MedWatch will not be needed. \nIn terms of introduction of nirsevimab in the context of coming out of a pandemic during which \nthere have been many conversations about vaccine confidence and demand, it is not clear \nwhether physicians and the public will accept this new product and/or what the demand would \nbe. In addition, this is occurring at the same time as commercialization of COVID -19 vaccine \nand seasonal influenza vaccine administration. Vaccine hesitancy and the need for counseling \n15 \n \n       \n  \n  \n \n  \n    \n \n  \n  \n  \n   \n \n \n \n     \n      \n    \n     \n \n     \n   \n  \n \n   \n     \n  \n   \n   \n    \n  \n \n    \n   \n     \n \n   \n  \n   \n \n \n    \n    \n    \n   \n     \n    \n   \n \n \n      \n  are anticipated regarding all vaccines and products. In addition, there have been efforts to \nweaken school immunization requirements and expand vaccine exemptions at the state level. \nThis also feeds into vaccine confidence and demand issues. \nIn conclusion, this summarizes just some of the potential issues with implementation of \nnirsevimab . The risks during this season’s rollout include timing of availability of doses, provider \nhesitancy, and uptake. The recommendations will be complex with regard to hospital versus outpatient administration and seasonality and timing. Lessons learned with respect to hepatitis \nA and B should be considered. In addition, there may be unintended consequences. Therefore, \nit is important that all partners involved in this are thinking through potential implementation \nissues moving forward to ensure that the product has good uptake and infants are protected. \nDiscussion Points \nDr. Poehling requested that the FDA or the vaccine manufacturer share the list price and \nbounds in the most recent iteration. B ecause there is availability of the product in 2 formulations \n(e.g., 50 mg and 100 mg) she asked for confirmation that they both would be priced the same in \norder to ensure that infants can receive the appropriate dosing without an additional cost \nconcern.  Another potential concern that Dr. Peacock raised regarding the CPT code defining \nnirsevimab as a drug or therapeutic. While the ACA covers vaccines, there are a lot of private \ninsurance plans that have high deductibles. This raised a concern about whether large co -pays \ncould be anticipate d for many families . \nDr. Ritch ey responded that Sanofi Vaccines is committed to making Beyfortus ™ successful and \ncost- effective for all infants entering their first RSV season. Consistent with the analysis shared \nby ACI P and the WG, a ssuming an all -infant recommendation and inclusion in the VFC program \nto ensure access for those infants, Sanofi Vaccines’ pricing will be cost- effective with a \ncommercial list price of $495 and a lower VFC price of $395 to reflect that volume that is \npurchased through the program. The 50 mg and 100 mg formulations would be $495, which \nmeans that 2 doses given for 200 mg would be $990. In terms of private insurance and the potential for high co- pays, Dr. Peacock reached out to \nbilling expert s and reported that nirsevimab would be covered under the ACA as an \nimmunization with no co -pay if it is recommended by the ACIP . \nDr. Talbot asked whether the AMA would reconsider its classification of nirsevimab as a drug \nand therapeutic. When the term “drug and therapeutic” is used, patients are going to think that \nthis is a treatment for RSV rather than a prevention. This will make educating families much \nmore difficult. As a member of the WG, Ms. Stinchfield (NAPNAP) thanked Dr. Peacock for outlining the \nsignificant implementation challenges discussed with the WG . Coming from the private sector \nhospital and clinic setting s, she encouraged all of her colleagues across the US to use Dr. \nPeacock’s very detailed presentation as a template f or the work that needs to be done and \nstarting now with the patient education, staff education, storage and handling, electronic medical \nrecords (EMRs), et cetera . The numerous considerations for implementation should not be \nbarriers. They are just going to take some work beginning immediately . \nDr. Hopkins (NFID) emphasized that addressing potential issues around collaboration and \ncommunication would be critical to do as soon as possible with regard to this product and for \nRSV prevention in infants in general. \n16 \n \n  \n        \n       \n    \n    \n \n    \n     \n      \n      \n        \n      \n    \n   \n    \n \n \n      \n   \n   \n     \n \n     \n     \n      \n      \n     \n    \n     \n      \n \n \n        \n     \n   \n     \n   \n     \n \n   \n      \n \n \n  \n   \n \n    \n  \n     Regarding the cost -effectiveness results for children 8─19 months of age, Dr. Cieslak (CSTE) \nsaid he was surprised to see that the WG thought the costs were reasonable. He asked Dr. \nJones to explain the risk category for the base case scenario and the rationale for apparently \nupping that 10-fold in the sensitivity analysis. \nDr. Jones indicated that the baseline risk was based on those who would be entering their \nsecond RSV season in October who would be 8─19 months of age per NVSN rate s for the \ngeneral population. Because the analysis was considering those at increased risk and there was \na lack of data on what the hospitalization rate would be for these increased risks, theoretical risk \ngroups were created to estimate what the rates may be. This was the reason the WG did not \nexpand beyond those who already were recommended to receive palivizumab. Instead using \npalivizumab as a 5-dose monthly monoclonal antibody product for those who are recommended \nto receive palivizumab , switching them to nirsevimab would be assumed to be a cost-saving in \nthat scenario. That is the scenario the WG interpreted as being a reasonable allocation of \nresources. \nDr. Loehr asked Dr. Jones to clarify if Slide 55 was saying that some people have a higher risk \nbut there are no data. He asked for clarification about whether there were any data on the \nchildren who received palivizumab to give them a sense of how much more likely they are to be \nin the hospital than the average 12 -month -old or 18- month -old. He agreed that switching to \nnirsevimab would be very expensive if the increased risk is not significant. \nDr. Jones responded that the lack of data on the increased incidence rate of hospitalization or \nother health outcomes for those at increased risk is most concerning. Based on the lack of data \nin a review of the evidence, the AAP recommends palivizumab only in the second season for a \nfairly select group. The WG reviewed that paper and did the systematic review, and found a \nvery limited set of data that show ed an increased risk of 2, 4, and 4 times the risk. The \nMarket Scan analysis show ed higher prevalence ratios of hospitalization, but the WG had \nconsiderable concern about whether those represent the truth or if those are inflated due to \nRSV testing of high- risk populations versus the general population. Given the lack of data, the \nWG did not have confidence in what the rates would be. \nDr. Loehr agreed that if nirsevimab is on the immunization schedule, it will get covered without \nco-pay under the ACA. However, he reiterated something he has brought up many times. This \nwill take time. He just had to research this for a presentation and confirmed that insurance \ncompanies have 1 year after approval and until the following plan year. If ACIP approv ed a \nproduct in February 2023, insurance plans would have until February of 2024 to cover it without \ncost. If the ACIP approved nirsevimab during this meeting, it could be 18 months before it would \nbe covered. There are insurance companies that would begin covering it immediately upon \napproval of the ACIP’s recommendation by the CDC director. He encouraged insurance \ncolleagues to simply adopt that policy because it is in the best interest of patients and \ncommunities. \nDr. Lee invited Dr. Grubb from America’s Health Insurance Plans (AHIP) to comment on this, \nrecognizing that there is heterogeneity by health plan. \nFrom a state health department point of view, Ms. Bahta highlight ed that bundling as has been \ndone with hepatitis B may be a challenge going forward with only 10% of hospitals enrolled in \nthe VFC program. It would be a major onboarding project to get state programs enrolled in the \n17 \n \n     \n \n \n  \n    \n    \n       \n   \n \n   \n  \n     \n   \n  \n \n \n      \n   \n   \n \n      \n   \n     \n      \n    \n \n   \n    \n   \n   \n   \n      \n   \n  \n    \n \n   \n   \n \n    \n    \n    \n    \n \n \n     \n     \n   \n      \n  \n VFC program. There also would be major challenges in practically implementing screening for \neligibility. \nDr. Daley expressed appreciation for the additional thought and care the WG put into including \nAI/AN populations in terms of second season dosage. Given the data that were presented on 4 \nto 10 times the hospitalization rate during the second season, the argument is compelling. \nHowever, he wondered about the aspects of acceptability and feasibility whether there are any \ndata to speak to the ability to implement that as a strategy. Dr. Jones indicated that while they do not have any specific data points, they have be en in \ndiscussions with colleagues from the Indian Health Service (IHS) and CDC ’s Office of Tribal \nAffairs and Strategic Alliances (OTASA) that works with the agency’s tribal partners and are \ncontinuing to receive feedback. These clinical considerations are being proposed and a VFC \nvote was planned during this meeting, but there are always opportunities to receive more \nfeedback. Dr. Clark (IHS) reported that the IHS is in the process of evaluating the logistical implications of \nthis recommendation for the IHS system of care, including federal, tribal, and urban programs. \nThis is a high priority given the increased risk to the IHS’s patient population. \nDr. Poehling emphasized that as Dr. Peacock mentioned in her presentation, careful thought \nmust be given to the potential for an RSV vaccine recommendation for pregnant persons. This \nwould be the first time that a vaccine given to a pregnant person would make a modification \nnecessary in the vaccines that person’s child receive s. This has major implications for IISs and \nin terms of avoiding record scatter and duplication of efforts. \nDr. Lee pointed out that this is a new era with regard to thinking about prevention more broadly. \nIn terms of innovation, this is an important step forward for prevention activities . However, \nimplementation does take time and there are a lot of complexities with regard to this type of \nproduct.  This is one of the first products the ACIP is considering in this way . Everyone must \nwork together to consider how to set up implementation in systems across various settings . \nWhile this is going to be difficult in the short -term, this product will open up many more \nopportunities and will have major benefit s in the long- term. Recognizing that the numbers would \nbe small, she asked whether there are any data on immunocompromised populations to \nunderstand whether at 150 days , the level of immunity is durable. \nDr. Jones indicated that the company had a small safety trial in an immunocompromised \npopulation and called upon Sanofi Vaccines to comment further. \nDr. Christian Felter , Sanofi, reported that the immunocompromised study is ongoing. While \nthere are no additional data at this point, the pharmacokinetics of nirsevimab is consistent \nacross populations. Significant differences have not been observed in any populations. It is \nknown that the duration of protection lasts at least 50 days and there are signals that it may last \nlonger than that. \nMs. Rebecca Coyle (AIRA ) pointed out that Dr. Peaccock did a fabulous job of outlining many of \nthe challenges for IISs. About 80% of the data come from EHRs and pharmacy systems , which \nis a very heterogeneous group of systems. She cautioned that there will be challenges with \nEHRs in terms of how quickly EHRs can adopt this and enter it into their systems to be able to \nsend it to an IIS. \n18 \n \n   \n \n      \n    \n  \n       \n \n   \n   \n     \n      \n \n       \n   \n   \n     \n  \n    \n   \n      \n    \n     \n   \n \n  \n    \n   \n  \n  \n \n \n   \n   \n    \n \n   \n   \n \n   \n \n       \n    \n  \n   \n \n   \n   \n       \n          \n Proposed Clinical Consideration Updates for Nirsevimab \nJefferson Jones, MD, MPH , FAAP, CDR, USPHS (CDC/NCIRD Co -lead, Maternal/Pediatric\nRSV WG ) reviewed proposed clinical consideration updates for nirsevim ab. For the timing of \nnirsevimab, providers should target administration in the first week of life for infants born shortly \nbefore the start of the RSV season for infants <8 months of age and shortly before the start of \nthe RSV season for children 8─19 months of age who are at increased risk of severe RSV \ndisease. While the optimal timing for nirsevimab administration is shortly before the season, it \nmay be given at any time during the RSV season for age -eligible infants and children who have \nnot yet received a dose. Based on pre- pandemic patterns, this means nirsevimab could be \nadministered in most of the continental US from October through the end of March. \nBecause the timing of the onset , peak , and decline of RSV activity may vary by jurisdiction, \nproviders can adjust administration schedules based on local epidemiology. For infants born \nshortly before or during the RSV season, nirsevimab should be administered within 1 week of \nbirth. Administration can be during the birth hospitalizat ion or in the outpatient setting. Infants \nwith prolonged birth hospitalizations due to prematurity or other causes should receive \nnirsevimab shortly before or promptly after discharge. Tropical climates may have seasonality \nthat differs from most of the continental US or that is unpredictable. This may include Southern \nFlorida, Hawaii, Guam, Puerto Rico, the US Virgin Islands (USVI) , and the U S-affiliated Pacific \nIslands. In Alaska, RSV seasonality is less predictable, and the duration of RSV seasons is \noften  longer than the national average. Providers in these jurisdictions should consult state, \nlocal, or territorial guidance on the timing of nirsevimab administration . \nIn accordance with CDC's general best practices for immunizations, simultaneous administration of nirsevimab with age -appropriate vaccines is recommended. In clinical trials, \nwhen nirsevimab was given concomitantly with routine childhood vaccines, the safety and \nreactogenicity profile of the co- administered regimen was similar to the childhood vaccines \ngiven alone.\n23 When co -administered, nirsevimab is not expected to interfere with the immune \nresponse to other childhood immunizations.24 \nChildren 8–19 months of age are recommended to receive nirsevimab when entering their \nsecond RSV season because of increased risk of severe disease. This includes children with CLD of prematurity who required medical support (chronic corticosteroid therapy, diuretic \ntherapy, or supplemental oxygen) any time during the 6- month period before the start of the \nsecond RSV season ; children with severe immunocompromise; children with cystic fibrosis with \nmanifestations of severe lung disease (previous hospitalization for pulmonary exacerbation in \nthe first year of life or abnormalities on chest imaging that persist when stable) or weight -for-\nlength <10\nth percentile;  and AI/AN children. \nNirsevimab is recommended for infants <8 months of age born during or entering their first RSV \nseason, including those recommended to received palivizumab by the AAP .25 Nirsevim ab is \nrecommended for children 8─ 19 months of age with increased risk of severe RSV disease and \nentering their second RSV season, including those recommended to receive palivizumab by \n23 https://www.accessdata.fda.gov/spl/data/2 f08fa60- f674- 432d- 801b- 1f9514bd9b39/2f08fa60-f674- 432d- 801b- 1f9514bd9b39.xml \n24 Espocito Front Immunol. 2021 Aug 11;12:708939 \n25 American Academy of Pediatrics. Committee on Infectious Diseases [Respiratory Syncytial Virus.] In: Kimberlin DW, Barnett ED, \nLynfield R, Sawyer MH, eds. Red Book: 2021 Report of the Committee on Infectious Diseases. Itasca, IL: American Academy of \nPediatrics,  2021. \n19 \n \n      \n \n \n   \n  \n       \n      \n     \n     \n    \n    \n \n  \n \n      \n     \n    \n    \n  \n    \n   \n    \n   \n   \n       \n     \n   \n     \n    \n  \n  \n    \n     \n \n \n   \n   \n    \n    \n  \n     \n \n \n         \n    \n      \n     \n      \n \n   \n      \n  AAP. Per the FDA label, children who have received nirsevimab should not receive palivizumab \nfor the same RSV season.26 \nIn terms of precautions and contraindications, providers administering nirsevimab should follow \nACIP ’s general practice guidelines for immunization. Nirsevimab should not be administered to \npersons with a history of severe allergic reaction (e.g., anaphylaxis) after a previous dose or to a \nproduct component. As mentioned in an earlier presentation, AEs after administration of \nnirsevimab without co -administration with any vaccine can be reported to M edWatch online at \nwww.fda.gov/medwatch or by phone at 1 -800-FDA-1088. AEs or suspected AEs events \nfollowing co -administration of nirsevimab with any vaccine should be reported t o the VAERS \nand additional reporting of the same AE to MedWatch is not needed. \nWG Considerations / Proposed Recommendations \nJefferson Jones, MD, MPH , FAAP, CDR, USPHS (CDC/NCIRD Co -lead, Maternal/Pediatric\nRSV WG ) summarized WG considerations and presented the proposed recommendations. In \nterms of safety monitoring for nirsevimab , FDA will monitor safety reports submitted by patients, \nproviders , and the manufacturer to the FDA Adverse Event Reporting System (FAERS) and \nVAERS. FDA will monitor other data sources, including the scientific literature, the applicant ’s \nperiodic safety reports, ongoing clinical studies, and potential other sources (e.g., medical billing \nand EHRs) . CDC will monitor reports submitted to VAE RS that involve simultaneous \nadministration of nirsevimab with childhood vaccines and also will monitor the safety of \nnirsevimab in the Vaccine Safety Datalink (VSD). CDC will leverage existing vaccine \neffectiveness platforms. The NVSN is an active surveillance system for acute respiratory \ninfection (ARI) at 7 pediatric medical centers that can assess effectiveness against outpatient \nand ED visits and hospitalizations. This platform can capture nirsevimab receipt through parent \ninterviews, medical record reviews at the primary care provider and birth hospital, and through \nstate IIS s. Virtual SARS- CoV-2, Influenza, or other Respiratory Viruses Network (VISION ) is a \nmulti- site EHR- based network that can assess effectiveness against ED and urgent care vi sits, \nhospitalization, and critical illness. Nirsevimab effectiveness analyses will be limited to \nintegrated healthcare system sites that will have more complete capture of nirsevimab receipt \nthrough IIS linkage and claims data. CDC will monitor nirsevimab effectiveness throughout the \nseason, but end- of-season estimates likely will be the most accurate. The power to estimate \neffectiveness depends on n irsevimab uptake and RSV incidence. \nRSV genomic surveillance also will be important. Mutations resulting in nirsevimab resistance \nhave been rarely reported.27 Sanofi and AstraZeneca are sponsoring INFORM -RSV, a global \ngenomic surveillance study in children less than 5 years, to monitor evolution of RSV strains, F-\nprotein antigenic sites, and their relationships with clinical features of RSV disease.28 CDC is \nplanning genomic surveillance of pediatric and adult RSV specimens, including whole genomic \nsurveillance. This s urveillance will monitor for changes in the F- protein that might result in \nnirsevimab resistance. \nFor the indication for infants <8 months of age born during or entering the RSV season, the WG \nfound that nirsevimab is safe and effective in reducing the risk of RSV disease, including \nhospitalization due to RSV. The WG shared the concerns as outlined in the presentation by Dr. \nPeacock on implementation considerations. The WG felt that the use of nirsevimab would be a \nreasonable and efficient allocation of resources, but many WG members prefer a lower cost per \n26 https://www.accessdata.fda.gov/spl/data/2f08fa60- f674- 432d- 801b- 1f9514bd9b39/2f08fa60-f674- 432d- 801b- 1f9514bd9b39.xml \n27 Ahani et al. Nat Comm 2023 14:4347; and Wilkins et al. Lancet Infect Dis 2023; 23: 856– 66 \n28 Tabor 2020 Dec 17;59(1):e01828 -20 \n20 \n \n      \n    \n    \n      \n    \n    \n \n \n \n    \n     \n \n  \n  \n \n \n \n \n    \n   \n   \n \n \n     \n     \n    \n  \n   \n \n     \n   \n       \n   \n     \n      \n  \n \n      \n      \n     \n \n \n      \n     \n  \n \n     \n    \n   \n   dose. The WG felt that there were limited efficacy and safety data for the indication for children \n8─19 months of who had increased risk of severe RSV disease and were entering their second \nRSV season. Additionally, there were limited data on the burden of severe disease in the \nsecond RSV season for children with chronic conditions. Therefore, the WG supported the \nrecommendation of nirsevimab being given to children 8─19 months of age entering their \nsecond RSV season for those who are recommended for palivizumab by the AAP in their \nsecond RSV season and for AI /AN children as described in clinical considerations. The \nfollowing is the proposed ACIP voting language: \nInfants aged <8 months born during or entering their first RSV season are recommended \nto receive one dose of nirsevimab (50 mg for infants <5 kg and 100 mg for infants ≥5 kg) \nChildren aged 8– 19 months who are at increased risk of severe RSV disease and \nentering their second RSV season are rec ommended to receive one dose of nirsevimab \n(200 mg) \nDiscussion Points \nReferring to Slide 5, Dr. Loehr requested clarification that nirsevimab will not interfere with \nmeasles, mumps, and rubella (MMR) and varicella vaccines . In general, there are \nconsiderations for immunoglobulins and live vaccines. In addition, he asked for clarification \nabout when to start nirsevimab . \nDr. Jones replied that the WG had a presentation and discussion on this. The data are fairly \nlimited on nirsevimab bein g co- administered with vaccines and immunogenicity. Per discussions \nwith expert input from CDC immunologists, the risk appear s to be low . Per the FDA label and \nCDC’ s general best practices for immunization, the WG felt it appropriate to recommend co -\nadmini stration of nirsevimab for age- appropriate vaccines. \nDr. Natalie Thornburg emphasized that there are not a lot of data on co-administration of \nmonoclonal antibody prophylaxis with childhood immunization, given that they are not yet widely used. There are some data for infants who have received palivizumab, with no indication that \nthey interfere with vaccine responses. Most of the data that are available for co -administration of \nvaccines or inhibition of vaccines deal with live -attenuated vaccines. Obviously, this product is \nnot a vaccine. It is a passive immunization product for which the mechanisms of inhibitions are \nnot relevant. \nIn terms of when to start nirsevimab, Dr. Jones reiterated that the trials showed an efficacy of \n150 days and that there were some data suggesting that efficacy may last longer than 150 days. \nIt is important to try to time administration between October through March, which is shortly \nbefore the RSV season. Dr. Poehling request ed input from FDA or Dr. Shimabukuro about how they would collaborate \nwith the FAERS and VAERS systems in terms of ensuring that everything is captured and there \nis a complete picture . \nDr. S himabukuro responded that first and foremost, CDC work s closely w ith FDA to monitor \nvaccine safety. For n irsevimab, CDC has worked closely with the Center for Drug Evaluation \nand Research (CDER), the Center for Biologics and Research (CBER), and NCIRD to develop \na comprehensive monitoring approach. As mentioned, the home for possible AEs involving \n21 \n \n    \n    \n \n     \n    \n    \n  \n  \n      \n  \n \n \n    \n   \n       \n   \n    \n      \n \n \n   \n      \n  \n \n \n  \n  \n       \n  \n   \n   \n  \n \n    \n    \n  \n  \n       \n \n \n    \n      \n   \n   \n    \n \n   \n    \n     \n       \n nirsevimab will be the FDA ’s FAERS system . Reports involving nirsevimab and other vaccines \nwill be sent to VAERS. There is a process for addressing mis -routed reports. \nDr. Poehling stressed that the cost per dose was weighing heavily on her. While she understood \nthat these have been expensive studies and the company’s process needs to compensate for \nthat work, she remained concerned about equity. Hospitals will have 1 week to administer this \nand there will be a cost differential for a baby born in July versus one born in October. \nTherefore, it seemed prudent to have private practices administer it versus the hospital. Also \nexacerbating this issue is the rural -urban differential in that locations in rural Am erica would not \nhave access to this. \nDr. Sanchez emphasized that if nothing else was learned from COVID -19, it was that no one \nknows when the RSV seasons will start this year. Continued monitoring of local epidemiology \nwill help to understand when the opt imal time will be to start administering nirsevimab. In terms \nof implementation issues, this is a new medication that will be given to every infant <8 months of \nage. However, the benefit will be huge. The main issue for him is whether they will be able to \nget a supply for the coming season. Those who have been administering palivizumab really \nwant nirsevimab. While there will be issues of implementation, he does not think they will be \ninsurmountable. \nDr. Talbot expressed concern about nirsevimab being referred to interchangeably as a drug and \ntherapeutic even though ACIP is treating it as a vaccine. For the purpose of monitoring, \nconsiderable effort needs to be made to term this one way to prevent some of the co mplications \nthat will occur . \nDr. Daley noted that he had received some detailed questions from colleagues, such as whether \nit would be considered an administration error if a child who is 8.5 months old and is not in a \nhigh- risk group presents in December during a bad RSV season and receives nirsevimab. He \nalso stressed the importance of communication to providers about what to say when parents \nask whether nirsevimab is a vaccine. He feels like those conversations are going to come up \nthousands of times, and it would help providers to be able to answer this question in a \ntransparent, honest, and succinct way. \nDr. Jones indicated that the current recommendation is that n irsevimab is recommended for \nchildren less than 8 months of age. Having high- risk condit ions is an exception. Children 8–19 \nmonths who are at increased risk of severe RSV disease and entering their second RSV season \nare recommended to receive one 200 mg dose of nirsevimab . CDC is working on education and \nother materials to help providers and webinars and updated websites are planned for the near \nfuture. \nBased on the available evidence, Ms. McNally requested more information about whether there \nis any reason to believe that there would be harm to an infant if there was maternal vaccination \nand nirsevimab was given to the infant. In addition, she asked whether a Vaccine Information \nStatement (VIS) sheet would be provided to parents of infants receiving nirsevimab and what \nthe adjudication mechanism would be for claims of potential injury from nirsevimab. \nDr. Jones noted that questions referring to maternal vaccine are generally deferred pending \nFDA licensure of a maternal vaccine. Maternal antibody from infection is certainly present in \ninfants, and nirsevimab was likely given to infants born to mothers who were infected recently or \nduring pregnancy. The consensus is that there is not thought to be any risk from that. \n22 \n \n        \n   \n \n   \n    \n     \n   \n    \n   \n        \n   \n \n \n \n        \n     \n   \n      \n       \n   \n   \n    \n    \n   \n \n \n \n \n   \n  \n \n  \n \n \n    \n  \n   \n \n   \n  \n \n \n   \n   \n    \n     \n     \n     \n \n     \n Dr. Peacock indicated that there would be something similar to VIS sheet s. Because nirsevimab \nis not a vaccine, the sheet will be called something else but will look similar. \nDr. Grimes from the Health Resources and Services Administration (HRSA) indicated that for \nvaccines, the criteria for coverage is typically for routinely administered vaccines and \nadjudication is through the national Vaccine Injury Compensation Program (VICP) . That is when \na vaccine has been recommended by CDC for routine administration to children or pregnant \nwomen, subject to an excise tax by federal law, and added to the Vaccine Injury Table by the \nSecretary of HHS. The Vaccine Act that governs the VICP does not define “vaccine. ” Of those 3 \ncriteria are met, there is potential route for coverage within the VICP. The VICP and VFC \nprograms are separate. Inclusion in the VFC would not trigger i nclusion in the VICP or vice \nversa. \nDr. Lee praised the work that CDC is doing with AHIP , but expressed concern about the \nfinancing of prevention. While nirsevimab is a fantastic product that has not been available \npreviously and that has many benefits in terms of the durability of protection compared to other \nantibody products that have been used previously for high-risk children, there are challenges in \nthe ambulatory setting. Pediatricians , family p ractice doctors, and birthing hospitals essentially \nhave been asked to pay upfront for the cost of products, including vaccines , and then hope for \nadequate reimbursement. Pediatricians and family practitioners in small practices will be \nbearing the brunt the upfront cost and potentially losing money to be able to deliver these \npreventive interventions. In terms of thinking about more innovative strategies for prevention, \nshe put out a general plea for reconsideration of where the risk will occur. The high c ost is a \nburden and disincentive for getting people to do the right thing. Dr. Lee emphasized the critical \nimportance of aligning incentives and securing the ability to ensure adequate reimbursement, \neven at -cost reimbursement . \nDr. Grubb (AHIP) stressed that while activities would depend upon what the ACIP recommends , \ncompliance issues would be very similar to compliance issues for any other vaccine. She noted \nthat other members of AHIP had joined the meeting, and they would take the input back to AHIP. Th is is going to involve a multi -layered response because there are many questions with \nregard to issues, such as coding. AHIP looks forward to working with CDC and ACIP on these issues. \nDr. Kotton stressed that because nirsevimab is passive immunization, there could be issues \nentering administration into the immunization record and other places . For instance, it was \ndifficult to get Evusheld into the immunization records in Epic . \nDr. Jones replied that CDC is aware of this issue and continues to work with national and \ninternal partners to address it. \nDr. Poehling said that while she liked the voting language that was presented and recognized \nthat it was time- limited, ACIP was in a difficult position because FDA was currently reviewing a \nmaternal vaccine. The way she interpreted the language was that if the maternal vaccine is \nsubsequently approved, both nirsevimab and the maternal vaccine would be given. She \nstressed that she was not ready to make that decision during this meeting and request ed input \non the WG’s thoughts about how they thought the ACIP should address this. For example, would ACIP have to meet again to vote on maternal vaccine. \nDr. Jones reiterated that the WG would revisit the recommendation at such time that a maternal \nvacci ne is licensed by FDA. \n23 \n \n  \n  \n     \n \n     \n  \n      \n     \n     \n    \n   \n      \n \n  \n  \n   \n   \n \n    \n     \n    \n    \n   \n      \n       \n      \n    \n    \n   \n \n       \n    \n      \n     \n    \n  \n    \n    \n    \n \n     \n  \n    \n  \n    \n      \n    \n   \n  Dr. Lee confirmed that the ACIP would have to convene again to vote on a maternal RSV \nvaccine and discuss any implications related to the use of n irsevimab at that time. \nDr. Fryhofer (AMA) said that speaking as a practicing physici an, she applauded the WG’s \nrecommendation to include giving a dose of nirsevimab to AI/AN children in their second RSV \nseason. Based on the presentations, the rate of RSV hospitalization for these children is 4 to 10 \ntimes that of the general population. It also is known that the maternal mortality rates for their \nmothers are over twice as high as rates for white women. ACIP and p racticing physicians often \nhear about VAERS, but are not as familiar with FAERS . She was relieved to hear that CDC and \nFDA work so closely together to make sure that any reported concerns will be made available \nto the appropriate agency. In terms of CPT coding, she attended a meeting earlier in the year as \nAMA Board Chair of the AMA CPT Advisory Committee . The nuances discussed throughout the \nday in the ACIP meeting between vaccines and passive immunizations like nirsevimab have \nbeen anticipated and the issues are already being discussed. And as pointed out in Dr. \nPeacock's presentation, the issue about it not being eligible for standalone counseling is an \nimportant one that she will share with the AMA Advisory Committee. \nDr. Whitley -Williams (NMA) applauded the WG and presenters for their careful considerations \nand deliberations. She noted that she just returned from the national meeting of the National \nMedical Association (NMA) , which is comprised predominantly of African -American physicians. \nThe presentations during that meeting included a talk on RSV vaccines and another on nirsevimab , which were well-received. In attendance w ere pediatricians , physicians , \nacademicians , and inner city and rural providers . Concerns were raised about how nirsevimab \nwould be recorded and that registries may not be available in the rural areas. She urged that \nany communications emphasize the importance of the first of nirsevimab being given in the \nhospital prior to discharge, particularly in rural areas where nirsevimab may not be included as \npart of the armamentarium of medications. Also important is clear communication that this is a \nbiologic not a vaccine. \nDr. Loehr said he was looking forward to 2 years from now when this was all in the past. This is \na spectacular advancement that is going to help families and offices and keep children out of \nthe hospital that will be covered by insurance 2 years from now and all implementation activities \nwill be in place. While there will be growing pains, he emphasized that they should not lose sight \nof how important this advancement is. With regard to the vote language in front of the ACIP , he \nfavored the first proposal completely. He was wrestling with the second proposal, given that it \nwould be a very expensive proposal recommendation with a lot of extrapolations. However, he \nthought it would promote equity. While he had not decided yet how he would vote, he wanted to \nexpress his hesitation about the second proposal. \nIn terms of the second proposal, Dr. Long pointed out that the groups who are part of the AAP \nrecommendations are already receiving p alivizumab, which wou ld be much more expensive \nthan nirsevimab . The only expansion of the group would be to include AI/AN children who are at \n6 to 10 times higher risk for severe disease and hospitalization than the general population. The WG thinks that this would be a very small group of children of about 1% of the population of \nchildren 8─19 months. These children already are costing a lot of money because of \npalivizumab and there are not sufficient data to say that the indication for passive protection \nshould be removed for those who are already receiving palivizumab. \n24 \n \n  \n     \n      \n   \n \n \n    \n \n      \n      \n   \n   \n    \n     \n \n \n   \n   \n    \n  \n   \n \n    \n  \n \n     \n  \n     \n \n \n       \n    \n   \n \n    \n      \n  \n \n      \n    \n  \n    \n   \n  \n  \n \n     \n \n     \n          Dr. Jones added that the second indication is expected to be cost -saving for children who \ncurrently are recommended by AAP to receive palivizumab. A nother consideration for the AI/AN \nChildren is that there are many geographic areas where children who get severe RSV require \nemergency air transport to receive appropriate medical care, which was another consideration \nof the WG . \nMs. Howell indicated that she was representing the Association of Immunization Managers \n(AIM) , which is a membership association comprised of the 64 federally -funded state, territorial, \nand city health agencies that administer immunization programs at the local level that administer \nthe V FC locally and oversee the implementation of IISs. As a group, AIM has been anticipating \nnirsevimab availability for a while and has been looking forward to planning assumptions and \ncollaborating with CDC and others to overcome the challenges regarding implementation. She \npointed out that there is a fee cap in the VFC for the administration of vaccines that are included \nin the VFC, and asked whether the fee cap also would apply to nirsevimab even though it is \nbeing classified as a drug and not a vaccine. \nMs. Hance, Centers for Medicare and Medicaid Services ( CMS ) indicated that because \nnirsevimab would be administered under the VFC program, the vaccine administration fee \nceiling would have to apply. She explained that the ceiling is the amount a state Medicaid \nagency can reimburse a provider, and that a state Medicaid agency has the flexibility to set the \nrate up to that ceiling. \nDr. Poehling mad e a motion to approve the ACIP voting language as presented, which Dr. \nSanchez seconded. Dr. Hopkins (NFID) commented that the National Foundation for Infectious Diseases (NFID) has \nposted a number of educational materials on RSV and that following the actions of the ACIP on \nnirsevimab, they will continue to provide educational materials supporting providers , patients , \nand families going forward. Dr. Lee asked whether there is a minimum interval for children who might be eligible in their \nsecond RSV season, such as a child who is born at the end of season one but who a \npractitioner wants to protect through season two . \nDr. Jones responded that there is no minimal interval. Based on pre- pandemic seasonality, \nhigh- risk infant s born at the end of March would be a little over 6 months before the beginning of \nOctober when the second RSV season would start. \nIn terms of equity, Dr. Daley pointed out that there is a risk of making health equity worse or \nincreasing inequity with a new product that has so many challenges. While there appears to be a great opportunity to improve health equity with nirsevimab, it is extremely important to \nconsider those who are coming from a more disadvantaged situation, such as living in a rural area of the country. Regarding implementation, he asked Dr. Peacock to speak to how the ACIP \ncould help with some of the challenges she raised in her presentation and whether there were \nany other issues the committee should discuss during this public session. \nDr. O ’Leary, Pediatric Infectious Diseases Society (PIDS), noted that many of the PIDS \nconcerns were addressed during this session and expressed excitement about the potential to \nprevent many hospitalizations. PIDS is workin g internally and with its partners in the federal, \nstate , and local governments to focus on the issue of equity as this product is rolled out. AAP \n25 \n \n   \n   \n \n   \n   \n  \n   \n  \n   \n       \n  \n    \n      \n      \n       \n    \n \n \n   \n \n    \n   \n    \n   \n  \n      \n  \n \n   \n   \n \n \n  \n \n \n   \n   \n    \n    \n \n \n \n   \n  \n \n   \n    \n \n   \n   also is working on potential implementation issues and barriers, including communications and \ncrafting implem entation guidance for its partners. \nDr. Peacock expressed appreciation for all of the comments and the recognition that \nimplementation is going to be challenging. It is important to remember that this is a new and very exciting product , and this is going to be a transitionary season. She captured a list of \nimportant issues raised related to insurance, coding, equity, et cetera. The VFC is an example \nof a program that has successfully addressed health equity issues over the last 30 years. It \nprovides access not only to children who are on Medicaid, but also children who are under -\ninsured or uninsured and AI/AN children. All of these considerations are very important, and it \nwill be necessary to work hand- in-hand with vaccine providers, physicians, nurses, health \ndepartments, and others who are involved to ensure that as much access as possible is \nprovided during the initial implementation and moving forward. It appears that this season may \nbe different from the last couple of years. As a reminder, hepatitis B began with a different \nrecommendation and eventually became given regularly in hospitals. In the near -term with the \nrollout, more nirsevimab may be given in the o utpatient setting. It is important to take a step \nback and appreciate that this is an amazing time in terms of RSV. \nVaccines for Children Resolution \nJeannie Santoli, MD, MPH (CDC/NCIRD) explained that the purpose of this resolution was to \nadd the monoclonal antibody preparation n irsevimab for infants to prevent RSV disease to the \nVFC program. The first eligible group is infants <8 months of age born during or entering their \nfirst RSV season. The second eligible group is children 8─19 months of age as noted in Table 1 \nwho are at increased risk of severe RSV disease and entering their second RSV season. Table \n1 describes children at increased risk of severe RSV disease and Table 2 explains the \nrecommended immunization schedule and dosage intervals . \nFor recommended dosage, readers are referred to the product package insert. For \ncontraindications and p recautions , readers are referred to the package inserts available at: \nhttps://www.accessdata.fda.gov/spl/data/2f08fa60 -f674-432d- 801b -1f9514bd9b39/2f08fa60-\nf674- 432d -801b- 1f9514bd9b39.xml . \nThe following standard statement regarding updates based on published documents also is included in the resolution: \n[If an ACIP recommendation or notice regarding RSV prevention is published within 6 months \nfollowing this resolution, the relevant language above (except in the eligible groups sections) will be replaced with the language in the recommendation and incorporated by reference to the \npublication URL.] \nDiscussion Points \nReferring to Slide 10, Dr. Daley suggested working on the wording of the timing. While he \nthought they knew what was intended, it could be clearer. \nDr. Kotton’s requested further clarification of what was meant by “ children with severe \nimmunocompromised” meant and asked whether further definitions would be provided. \nDr. Jones replied that initially, specific examples were included. However, there was concern \nthat if the recommendations were overly prescriptive, it may miss others who would qualify. \n26 \n \n  \n   \n \n \n    \n   \n   \n    \n    \n    \n  \n  \n \n \n \n \n      \n \n \n     \n    \n  \n   \n \n \n     \n  \n \n \n  \n   \n \n \n \n  \n \n     \n     \n  \n \n  \n \n   \n \n  Dr. Long added that those caring for immunocompromised patients are the best ones to make \nthese decisions. \nDr. Kotton advocated for clinicians to have some type of guidance, but then leave a more open \nclause like, “ as well as other children deemed to be severely immunocompromised by their care \nteam.”  She stressed that clinicians have been clamoring for fairly specific guidance from the \nCDC regarding immunization recommendations, as it can be hard to fully understand what the \nrecommendations mean. From her perspective, further guidance could be useful. Outstanding \nguidance was provided by the CDC during the COVID -19 pandemic regarding the definition of \nwho is moderately to severely immunocompromised, which she thought changed the field for \nthe better. She suggested including additional input. \nDr. Lee agreed that it would be extremely beneficial to have at least some “big picture” guidance \non that in the C linical Considerations . \nMs. Goode (APhA) requested clarification on the second vote language about whether someone \nreceiving a dose in the first season before 8 months of age should receive a second dose in the \nsecond season . \nDr. Jones clarified the recommendations were independent,  with the second pertaining to \nchildren at increased risk. The FDA label specif ies that those who received palivizumab in their \nfirst RSV season can receive n irsevimab in their second RSV season. There are no \ndisqualifications for the second RSV season related to what did or did not happen in the first \nRSV season. \nDr. Long stressed that this was somewhat confusing, but the WG wanted to be sure not to use \nthe words “second dose” so that the recommendation would not be misinterpreted as 2 doses \nbeing needed. \nDr. Poehling made a motion to accept the VFC R esolution as proposed with the clarification in \nthe table as noted during the discussion. Dr. Sanchez seconded the motion. \nPUBLIC COMMENTS \nOverview \nThe floor was opened for public comment on August 3, 2023 at 2:00 PM ET. Given that many \nmore individuals registered to make oral public comments than could be accommodated during \nthis meeting, selection was made randomly via a lottery. Dr. Lee provided a gentle reminder that \nthe ACIP appreciates diverse viewpoints that are respectful in nature and issue- focused rather \nthan comments directed at individuals. The comments made during the meeting are included in this document. Members of the public also were invited to submit written public comments to \nACIP through the Federal eRulemaking Portal under Docket Number ID CDC -2023- 0063. Visit \nhttp://www.regulations.gov for access to the docket or to submit comments or read background \ndocuments and commen ts received. \n27 \n \n  \n \n    \n \n \n     \n     \n   \n        \n     \n    \n  \n     \n    \n   \n  \n    \n      \n    \n      \n    \n       \n       \n      \n   \n     \n \n    \n  \n \n  \n   \n  \n  \n \n  \n  \n   \n    \n   \n  \n   \n  \n      \n  \n   \n  \n    \n  \n \n     Public Comments \nMs. Susan Hepworth\nNational Coalition for Infant Health \nThank you so much and thank you for this opportunity to make these comments on behalf of the \nNational Coalition for Infant Health . We are made up of more than 200 professional, clinical, \ncommunity health, and family support organizations —all with the focus of improving the lives of \nall infants and their families. I just first want to thank the committee for prioritizing this review of \nthis immunization. I know the committee has undertaken so much over the last few years \nthroughout the public health emergency, so we appreciate your prioritizing this review among \nwhat I know are many other competing priorities. We are incredibly pleased and want to thank \nyou for voting in favor of the VFC resolution. This is a huge step toward ensuring equitable \naccess a nd reducing the burden of RSV. I would like to make one additional comment and that \nis the coalition ’s strong support of equitable and timely access to this prevention in hospitals, \nbirthing centers, and provider settings. I know this was something that was included in a recent \nletter from the American Academy of Pediatrics as well. With strong, clear guidance and \nrecommendations from the CDC for babies to receive this new immunization prior to being \ndischarged from the hospital, all babies will have the opportunity to be immunized and protected \nbefore they even leave the hospital setting. I think this measure is what is truly going to ensure \nequitable access for all infants, and it is also going to ensure a major reduction in the burden of \nRSV. As has been spoken about in prior meetings, the burden of RSV is multifaceted. It is not \njust medical, but it is emotional, and it is financial for families as well. With clear guidance, I \nthink we will be able to ensure that we will not have further existing health disparities. I just want \nto thank you all for what you do to protect and improve the health and safety of our nation’s \ninfants and childr en. Thank you for the opportunity to give these comments. \nLaura Burns Transplant Recipients and Immunocompromised Patient Advocacy Group \nMy name is Laura Burns and I represent TRAIPAG, Transplant Recipient and \nImmunocompromised Patient Advocacy Group. Being immunocompromised and vulnerable to \ndisease, we have a deep sense of kinship with the infants so vulnerable to RSV. We urge you to protect these children and to recommend nirsevimab for RSV prevention. It has been approved \nby the FDA and, with your vote, it will be covered by insurance as required under the ACA. But \ninsurance only covers about 50% of babies, so ACIP members, we intrigue you to resolve that \nnirsevimab be added to the Vaccines for Children program so that all babies can be protected. \nNirsevimab would be the first passive immunization product to be included in the CDC \nImmunization Schedule, but we think that there is little distinction to be made between active \nand passive immunization. The key is what prevents disease. Indeed, Congress sees it this \nway, too. Under 26 USC 4132, the term \"vaccine\" means “any substance designed to be \nadministered to a human being for the prevention of one or more diseases.” Nirsevimab fits that \nbill. Looking to the future, TRAIPAG anticipates you will be faced with a similar decision greatly \naffecting our health. Our group represents people of all ages, from people with blood cancers, \nautoimmune diseases, organ transplants. Since most of us have low or no response to vaccines, in all fairness, we need alternative preventions. A number of monoclonal antibodies, \nfor example, are in development for the prevention of COVID: Invivyd, AstraZeneca \nSUPERNOVA 3152. Also, antivirals. If one or more of them “passes muster” with the FDA, we \nhope that ACP will show the same deliberative care for vulnerable adults that you’re showing \ntoday for infants and that you recommend passive immunizations when they work. This in turn would guarantee that insurance will cover it. Likewise, as there is no vaccines for adults \n28 \n \n    \n \n \n   \n  \n  \n   \n \n \n  \n   \n \n \n \n \n \n    \n    \n      \n   \n   \n    \n  \n      \n    \n   \n     \n     \n       \n   \n    \n   \n    \n     \n     \n  \n     \n      \n      \n     \n      \n    \n     \n      \n  \n   \n      \n     \n   \n    \n program yet, the CDC should include whichever preventions work, active or passive, in both the \nbridge access and the VFC programs. This will ensure equity and that everyone, child or adult, \nwill have affordable access to life- saving immunizations at least through 2024. Thinking back, I \nwant you to know that Evusheld was a godsend for us and for our families and friends who got to be with us. So was REGEN -COV for post -exposure prophylaxis (PEP) before that. \nUnfortunately, not all of us had access. With commercialization, equitable access is an even \nlarger issue, but one you should tackle. If you will indulge me for just a few seconds, Dr. Lee, we \nwere truly heartened by your comments today earlier about how groundbreaking this step is and \nhow it opens up new avenues for preventing disease in the immunocompromised. While it may \nbe initially complicated, it will be well worth working through those issues. Thank you and thank \nyou all very, very much for all you do. We urge you to vote “yes” on all of these. \nClaire Hannan \nExecutive Director \nAssociation of Immunization Managers \nGood afternoon and thank you for the opportunity to comment on the potential implementation \nof the RSV monoclonal antibody, nirsevimab. We are excited that this groundbreaking opportunity to protect infants from RSV. I’m Claire Hannan, Executive Director of the \nAssociation of Immunization Managers , or AIM. AIM is a membership association whose \nmembers direct the immunization programs in the 64 federally -funded state, territorial, and local \nhealth agencies. In partnerships with CDC, these jurisdictions administer the Vaccines for \nChildren , or VFC , program and work to assure protection of the population through vaccination. \nLast week, we polled jurisdictions about their ability to incorporate nir sevimab into their \nprograms, including the Vaccines for Children program, and you’ ve discussed this mightily today \nalready . Among respondents, 52% report that their immunization information systems can \ndocument nirsevimab, 22% cannot , and 26% report that it is unknown. Reported challenges \ninclude lack of funding for the IIS vendor and lack of information on coding. 68% report that their \nIIS can be used for ordering nirsevimab in the VFC program, 14% that their IIS cannot be used, \nand 18% report unknown. Additional time and funding were the cited barriers to incorporate into \nIIS ordering applications. Additional challenges cited in the poll include the lack of participation \nof birthing hospitals in the VFC program, concern about data exchange between electronic \nhealth records and IIS, and lack of adequate time and guidance to prepare. The poll \ndemonstrates that time and funding are needed to incorporate this new product into VFC and \nother existing programs. However, the jurisdictions have not received guidance or assumptions \nto prepare for potential recommendation, such as the information needed to incorporate \nnirsevimab into VFC ordering applications and packaging and storage information. Jurisdictions \nhave not been able to hold discussions with CDC or IIS vendors to address challenges with \ncoding and tracking. What is most concerning to the incorporation of this potentially life -saving \nproduct into existing childhood programs is that jurisdictions have suffered an average loss of \n20% in funding for their IIS due to rescission of COVID funds. ACIP is holding this s pecial \nmeeting in August in order to vote on this life- saving product in time for the upcoming flu and \nRSV season. However, jurisdictions responsible for implementation have not been involved in \nthe planning discussions. The lack of federal communication to and coordination with jurisdiction \nimmunization programs continues to impact the ability of immunization program managers to roll \nout new and important products with maximum impact. They cannot be expected to deploy \ncritical products such as nirsevimab without the information and time needed to execute these \nprograms. We urge our federal partners to find ways to work with jurisdictions and provide \nplanning assumptions earlier in the process and to share critical information as it becomes \navailable. Thank you so much for the opportunity to comment today. \n29 \n \n  \n \n     \n  \n \n \n   \n \n  \n           \n \n  \n \n   \n     \n \n  \n \n \n \n \n    \n \n    \n   \n    \n    \n   \n \n             \n         \n        \n \n \n \n \n    \n \n   \n  \n \n    \n  \n \n             \n         \n        \n \n \n VOTES \nDr. Grace Lee (ACIP Chair) pointed out that while the votes for the recommendations were \nmoved and seconded together, the ACIP would vote on each proposed recommendation and \nthe VFC Resolution separately: \nVote #1 RSV Maternal/Pediatric Recommendations \nInfants aged <8 months born during or entering their first RSV season are recommended to \nreceive one dose of nirsevimab (50 mg for infants <5 kg and 100 mg for infants ≥5 kg). \nVote #2 RSV Maternal/Pediatric Recommendations \nChildren aged 8– 19 months who are at increased risk of severe RSV disease and entering their \nsecond RSV season are recommended to receive one dose of nirsevimab (200 mg). \nVote #3: VFC Resolution: RSV Maternal/Pediatric \nApprove the Vaccines for Children (VFC) Resolution for nirsevimab. \nMotion/Vote #1 RSV Maternal/Pediatric \nDr. Poehling made a motion to amend the proposed Vote #1 recommendation stating , “Infants \naged <8 months born during or entering their first RSV season are recommended to receive one \ndose of nirsevimab (50 mg for infants <5 kg and 100 mg for infants ≥5 kg). Dr. Sanchez \nseconded the motion. No COIs were declared. The motion carried with 10 affirmative votes, 0 \nnegative votes, and 0 abstentions. The disposition of the vote was as follows: \n10 Favored: Bahta, Chen, Daley, Lee, Loehr, Long, McNally, Poehling, Sanchez, Talbot \n0 Opposed: N/A \n0 Abstained: N/A \nMotion/Vote #2 RSV Maternal/Pediatric \nDr. Poehling made a motion to amend the proposed Vote #2 recommendation stating , “Children \naged 8–19 months who are at increased risk of severe RSV disease and entering their second \nRSV season are recommended to receive one dose of nirsevimab (200 mg). ” Dr. Sanchez \nseconded the motion. No COIs were declared. The motion carried with 10 affirmative votes, 0 \nnegative votes, and 0 abstentions. The disposition of the vote was as follows: \n10 Favored: Bahta, Chen, Daley, Lee, Loehr, Long, McNally, Poehling, Sanchez, Talbot \n0 Opposed: N/A \n0 Abstained: N/A \n30 \n \n  \n     \n \n    \n    \n      \n     \n \n             \n  \n         \n        \n \n \n \n \n   \n   \n \n \n     \n    \n      \n       \n  \n    \n     \n    \n \n \n     \n     \n       \n \n       \n    \n  \n  \n      \n \n \n  \n  \n   \n  \n   \n   \n    \n    \n Motion/Vote #3: VFC Resolution RSV Maternal/Pediatric \nDr. Poehling made a motion to amend the proposed Vote #3 recommendation for the VFC \nResolution stating , “Approve the Vaccines for Children (VFC) Resolution for nirsevimab. ” Dr. \nSanchez seconded the motion. No COIs were declared. The motion carried with 11 affirmative \nvotes, 0 negative votes, and 0 abstentions. The disposition of the vote was as follows: \n11 Favored: Bahta, Chen, Daley, Kotton, Lee, Loehr, Long, McNally, Poehling, Sanchez, \nTalbot \n0 Opposed: N/A \n0 Abstained: N/A \nDiscussion Points \nDr. Talbot expressed her excitement about nirsevimab, which she thinks will be incredible and \nlife-changing. She emphasized that as had been pointed out , there are a lot of logistics to work \nout. Dr. Long recognized the remarkable, committed work of the WG who engaged in many \ndiscussions about all of the issues raised during this meeting. She felt that the WG thoroughly \ndealt with what they could based on the available data and their best assumptions for the \nunknowns. This is a milestone in that it is the first antibody protection against the remark ably \nhigh remaining burden of disease in children, so parents should be relieved that they will not \nhave to be concerned about the likelihood that their children could be hospitalized with RSV \ndisease. As with every breakthrough, there is the feeling of responsibility and the burden that \nthis is the firs t time an antibody will be administered universally. All of the safeguards are in \nplace and there have been no signals of AEs within the small trials that were conducted. The \nWG also does not believe there is any biologic plausibility that there will be any interference with \nany immunization or live virus vaccine. The WG was extraordinar ily disappoint ed w ith the price-\nsetting of the manufacturer and wanted to assure the ACIP and public that should a maternal \nvaccine be licensed, the WG will address the cost issue of that product as well. \nDr. Sanchez agreed that this is great and exciting news for a product that everyone has been \neagerly awaiting. There has been considerable experience with palivizumab, which has to be \ngiven monthly and has high costs as wel l. Practitioners have been waiting to be able to give \nsafe and effective protection to every baby and this is fantastic news. While this is just the first \nstep, it is an extremely important step in the right direction for the major public health problem of \nRSV. \nDr. Lee echoed all of the comments regarding what an amazing milestone this is, emphasized \nthe importance of continuing to monitor ongoing effectiveness and safety, and pointed out the \nimportance of the ACIP hearing updated presentations in the future to demonstrate that there is follow- up on these specific areas and the impact of implementation on equity. While she \nrecognized that implementation is not necessarily the purview of the ACIP, how nirsevimab use \ngets implemented and its impact on equity may impact how the ACIP rethink s recommendations \nin the future. She expressed gratitude to the CDC team, the FDA team, the WG, and everyone \nelse who has done a phenomenal job steering this through and getting this product to market. \n31 \n \n      \n     \n     \n   \n    \n   \n        \n  \n \n     \n    \n   \n     \n   \n  Dr. Daley thank CDC colleagues for their work on getting the ACIP to the point at which they \ncould vote on a VFC Resolution for nirsevimab. He suspected that it was not an easy \nundertaking. He emphasized that the f olks within CDC are tremendously devoted to public \nhealth and have been doing everything they could to make this happen. He recalled that during \nthe February 2023 ACIP meeting, this looked somewhat more daunting, yet now they had voted \non the recommendations and the VFC Resolution . He expressed gratitude to those who saw \nthis as so important to include this in the VFC Program in order to provide the maximum public \nhealth benefit for RSV. \nDr. Romero added his thanks to the members of the ACIP and the WG for all of the deliberation \nand work they all put into this effort. This marked a historic event and he thought they would be able to look back in a short period of time and see what a major impact this vote has had on the \nhealth and well -being of children in the US. He said he thought this would mark one of the major \naccomplishments of the ACIP, for which he congratulated the committee. \n32 \n \n  \n \n    \n    \n  \n \n  CERTIFICATION \nUpon reviewing the foregoing version of the August 3, 2023 ACIP meeting minutes, Dr. Grace \nLee, ACIP Chair, certified that to the best of her knowledge, they are accurate and complete. \nHer original, signed certification is on file with the Management Analysis and Services Office \n(MASO) of CDC. \n33 \n \n  \n  \n \n  \n   \n  \n  \n    \n  \n   \n \n  \n  \n  \n \n \n \n  \n  \n  \n  \n  \n   \n    \n  \n    \n  \n   \n   \n  \n  \n \n  \n    \n   \n  \n  \n  \n   \n  \n  \n   \n    \n    \n  \n  \n \n  ACIP MEMBERSHIP ROSTE R \nCHAIR \nLEE, Grace M, MD, MPH \nAssociate Chief Medical Officer for Practice Innovation Lucile Packard Children’s Hospital \nProfessor of Pediatrics, Stanford University School of Medicine \nStanford, CA \nTerm: 8/4/2021 – 6/30/2023 \nEXECUTIVE SECRETARY \nWHARTON, Melinda, MD, MPH \nNational Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention \nAtlanta, GA \nMEMBERS \nBAHTA, Lynn, RN, MPH, CPH \nImmunization Program Clinical Consultant \nInfectious Disease, Epidemiology, Prevention & Control Division \nMinnesota Department of Health Saint Paul, Minnesota \nTerm: 7/1/2019 – 6/30/2023 \nCHEN, Wilbur H, MD, MS, FACP, FIDSA \nProfessor of Medicine \nCenter for Vaccine Development and Global Heal th \nUniversity of Maryland School of Medicine Baltimore, MD \nTerm: 12/23/2020 – 6/30/2024 \nDALEY, Matthew F, MD Senior Investigator \nInstitute for Health Research, Kaiser Permanente Colorado \nAssociate Professor of Pediatrics University of Colorado School of Medicine \nAurora, CO \nTerm: 1/4/2021 – 6/30/2024 \nKOTTON, Camille Nelson, MD, FIDSA, FAST \nClinical Director, Transplant and Immunocompromised Host Infectious Diseases \nInfectious Diseases Division, Massachusetts General Hospital \nAssociate Professor of Medicine, Harvard Medical School \nBoston, MA Term: 12/23/2020 – 6/30/2024 \n34 \n \n  \n  \n \n   \n  \n  \n  \n \n  \n \n \n   \n  \n   \n \n \n \n   \n \n  \n \n \n  \n  \n \n   \n  \n  \n  \n    \n   \n  \n  \n    \n   \n \n   \n  \n  \n \n  \n  LOEHR, Jamie, MD, FAAFP \nOwner, Cayuga Family Medicine Ithaca, New York \nTerm: 7/26/2021 – 6/30/2025 \nLONG, S arah S, MD \nProfessor of Pediatrics \nDrexel University College of Medicine Section of Infectious Diseases \nSt. Christopher’s Hospital for Children \nPhiladelphia, Pennsylvania \nTerm: 12/24/2020 – 6/30/2024 \nMCNALLY, Veronica V, JD \nPresident and CEO Franny \nStrong Foundation \nWest Bloomfield, Michigan Term: 10/31/2018 – 6/30/2022 \nPOEHLING, Katherine A, MD, MPH \nProfessor of Pediatrics and Epidemiology and Prevention Director, Pediatric Population Health Department of Pediatrics \nWake Forest School of Medicine Winston- Salem, NC \nTerm: 7/1/2019 – 6/30/2023 \nSÁNCHEZ, Pablo J, MD Professor of Pediatrics \nThe Ohio State University – Nationwide Children’s Hospital \nDivisions of Neonatal- Perinatal Medicine and Pediatric Infectious Diseases \nDirector, Clinical & Translational Research (Neonatology) Center for Perinatal Research \nThe Research Institute at Nationwide Children's Hospital Columbus, Ohio \nTerm: 7/1/2019 – 6/30/2023 \nTALBOT, Helen Keipp, MD \nAssociate Professor of Medicine Vanderbilt University \nNashville, TN Term: 10/29/2018 – 6/30/2022 \n35 \n \n  \n \n  \n    \n  \n  \n   \n   \n   \n  \n  \n \n    \n  \n  \n  \n   \n \n  \n  \n   \n  \n   \n  \n \n \n  \n   \n \n  \n \n  \n \n  \n   \n   \n  \n  \n  \n  \n   \n \n   \n  \n  \n  EX OFFICIO MEMBERS \nCenters for Medicare and Medicaid Services (CMS)\nHANCE, Mary Beth \nSenior Policy Advisor Division of Quality, Evaluations and Health Outcomes \nChildren and Adults Health Programs Group \nCenter for Medicaid, CHIP and Survey & Certification Centers \nfor Medicare and Medicaid Services \nBaltimore, MD \nFood and Drug Administr ation (FDA)\nFINK, Doran, MD, PhD \nDeputy Director, Clinical, Division of Vaccines and Related Products Applications \nOffice of Vaccines Research and Review \nCenter for Biologics Evaluation and Research \nFood and Drug Administration Silver Spring, MD \nHealth Resources and Services Administration (HRSA)RUBIN, Mary, MD Chief Medical Officer \nDivision of Injury Compensation Programs \nRockville, MD \nIndian Health Service (IHS)\nCLARK, Matthew, MD, FAAP, FACP \nPhysician \nChair, IHS National Pharmacy & Therapeutics Committee \nDurango, CO \nOffice of Infectious Disease and HIV/AIDS Policy (OIDP)\nKIM, David, MD, MA \nDirector, Division of Vaccines, OIDP \nOffice of the Assistant Secretary for Health Department of Health and Human Services \nWashington, DC \nNational Institutes of Health (NIH)\nBEIGEL, John, MD \nAssociate Director for Clinical Research \nDivision of Microbiology and Infectious Diseases \nNational Institute of Allergy and Infectious Diseases (NIAID) \nBethesda, MD \n36 \n \n  \n \n   \n  \n   \n  \n  \n  \n  \n   \n  \n   \n   \n  \n  \n  \n \n   \n \n  \n  \n  \n   \n  \n  \n    \n  \n  \n  \n  \n  \n   \n  \n  \n \n \n  \n   \n  \n  \n  \n  \n  \n   \n \n \n   \n  \n  LIAISON REPRESENTATIVES \nAmerican Academy of Family Physicians (AAFP)\nROCKWELL, Pamela G, DO \nAssociate Professor, Department of Family Medicine, University of Michigan Medical School \nMedical Director, Dominos Farms Family Medicine \nAnn Arbor, MI \nAmerican Academy of Pediatrics (AAP)\nMALDONADO, Yvonne, MD \nSenior Associate Dean for Faculty Development and Diversity \nProfessor of Pediatrics and Health Research and Policy \nChief, Division of Pediatric Infectious Diseases Stanford University School of Medicine \nStanford, CA \nAmerican Academy of Pediatrics (AA P) \nRed Book Editor \nKIMBERLIN, David, MD \nProfessor of Pediatrics \nDivision of Pediatric Infectious Diseases The University of Alabama at Birmingham School of Medicine \nBirmingham, AL \nAmerican Academy of Physician Assistants (AAPA)LÉGER, Marie -Michèl e, MPH, PA -C \nSenior Director, Clinical and Health Affairs American Academy of Physician Assistants \nAlexandria, VA \nAmerican College Health Association (ACHA)CHAI, Thevy S., MD  \nDirector of Medical Services \nCampus Health Services \nUniversity of North Carolina at Chapel Hill Chapel Hill, \nNC \nAmerican College Health Association (ACHA) (alternate) \nMCMULLEN, Sharon, RN, MPH, FACHA Assistant Vice President of Student & Campus Life for Health and Wellbeing Cornell Health Ithaca, NY \nAmerican College of Nurse Midwives (ACNM)HAYES, Carol E., CNM, MN, MPH Lead Clinician \nClinical Quality Compliance and Management \nPlanned Parenthood Southeast  Atlanta, GA \n37 \n \n    \n    \n \n  \n  \n   \n   \n    \n  \n   \n  \n  \n  \n    \n \n \n  \n \n \n  \n  \n  \n  \n    \n \n  \n  \n    \n   \n  \n  \n   \n \n \n  \n  \n  \n   \n  \n  \n  \n  \n   \n  \n  \n  \n \n  \n  American College of Nurse Midwives (ACNM) (alternate) \nMEHARRY, Pamela M., PHD, CNM \nMidwifery Educator, Human Resources for Health \nIn partnership with University of Rwanda and University of Illinois, Chicago \nAmerican College of Obstetricians and Gynec ologists (ACOG)\nECKERT, Linda O, MD, FACOG \nProfessor, Department of Obstetrics & Gynecology \nAdjunct Professor, Department of Global Health University of Washington \nSeattle, WA \nAmerican College of Physicians (ACP)\nGOLDMAN, Jason M , MD, FACP \nAffiliate Assistant Professor of Clinical Biomedical Science, Florida Atlantic University, Boca Raton, Florida \nPrivate Practice \nCoral Springs, FL \nAmerican Geriatrics Society (AGS) \nSCHMADER, Kenneth, MD Professor of Medicine- Geriatrics Geriatrics \nDivision Chief Duke University and Durham VA Medical Centers \nDurham, NC \nAmerica’s Health Insurance Plans (AHIP)\nGLUCKMAN, Robert A, MD, MACP Chief Medical Officer, Providence Health Plans \nBeaverton, OR \nAmerican Immunization Registry Association (AIRA) \nCOYLE, Rebecca, MSEd \nExecutive Director, AIRA \nWashington, DC \nAmerican Medical Association (AMA)\nFRYHOFER, Sandra Adamson, MD \nAdjunct Associate Professor of Medicine Emory \nUniversity School of Medicine \nAtlanta, GA \nAmerican Nurses Association (ANA)\nRITTLE, Charles (Chad), DNP, MPH, RN Assistant \nProfessor, Nursing Faculty Chatham University, School of Health Sciences \nPittsbu rgh, PA \n38 \n \n   \n \n  \n  \n  \n \n   \n   \n \n  \n \n \n  \n  \n    \n \n \n \n   \n  \n \n   \n  \n \n  \n  \n  \n  \n   \n  \n \n  \n   \n   \n    \n  \n   \n  \n  \n \n \n  \n  \n   \n   \n  \n  \n  \n  \n American Osteopathic Association (AOA) \nGROGG, Stanley E, DO \nAssociate Dean/Professor of Pediatrics \nOklahoma State University -Center for Health Sciences \nTulsa, OK \nAmerican Pharmacists Association (APhA)\nHOGUE, Michael D., PharmD, FAPhA, FNAP \nDean and Professor of Loma Linda University School of Pharmacy Director, Center for Interprofessional Education & Practice Loma Linda, CA \nAssociation of Immunization Managers (AIM)\nHOWELL, Molly, MPH \nImmunization Program Manager North Dakota Department of Health \nBismarck, ND \nAssociation for Prevention Teaching and Research (APTR) \nZIMMERMAN, Richard, MD, MPH \nProfessor \nUniversity of Pittsburgh School of Medicine \nDepartment of Family Medicine and Clinical Epidemiology Pittsburgh, PA \nAssociation of State and Territorial Health Officials (ASTHO)SHAH, Nirav D, MD, JD Director \nMaine Center for Disease Control and Prevention \nAugusta, ME \nBiotechnology Industry Organization (BIO)\nARTHUR, Phyllis A, MBA \nSenior Director, Vaccines, Immunotherapeutics and Diagnostics Policy Washington, DC \nCouncil of State and Territorial Epidemiologists (CSTE)\nHAHN, Christine, MD \nState Epidemiologist \nOffice of Epidemiology, Food Protection and Immunization Idaho \nDepartment of Health and Welfare Boise, ID \nCouncil of State and Territorial Epidemiologists (CSTE) (alternate) \nLETT, Susan, MD, MPH Medical Director, Immunization Program \nDivision of Epidemiology and Immunization \nMassachusetts Department of Public Health \nBoston, MA \n39 \n \n    \n  \n   \n   \n  \n \n \n   \n  \n  \n  \n  \n  \n \n    \n  \n  \n \n  \n  \n  \n  \n   \n  \n  \n     \n  \n \n \n  \n   \n  \n  \n   \n  \n  \n   \n  \n  \n \n  \n  \n  \n  \n  \n \n   \n \n  \n  Canadian National Advisory Committee on Immunization (NACI)\nDEEKS, Shelley, MD, MHSc, FRCPC, FAFPHM \nDeputy Chief Medical Officer of Health, Department of Health and Wellness, Nova Scotia \nAssociate Professor, Dalla Lana School of Public Health, University of Toronto \nChair, National Advisory Committee on Immunization \nHalifax, Nova Scotia \nInfectious Diseases Society of America (IDSA)\nBAKER, Carol J., MD \nProfessor of Pediatrics \nMolecular Virology and Microbiology Baylor College of Medicine \nHouston, TX \nInternational Society for Travel Medicine (ISTM)\nBARNETT, Elizabeth D, MD Professo r of \nPediatrics Boston University School of Medicine Boston, MA \nNational Association of County and City Health Officials (NACCHO)\nZAHN, Matthew, MD \nMedical Director, Epidemiology \nOrange County Health Care Agency \nSanta Ana, CA \nNational Associa tion of County and City Health Officials (NACCHO) (alternate) \nDUCHIN, Jeffrey, MD \nHealth Officer and Chief, Communicable Disease \nEpidemiology and Immunization Section Public Health - Seattle and King County \nProfessor in Medicine  Division of Allergy and Infectious Diseases \nUniversity of Washington School of Medicine and School of Public Health \nSeattle, WA \nNational Association of Pediatric Nurse Practitioners (NAPNAP)\nSTINCHFIELD, Patricia A, RN, MS, CPNP \nDirector Infectious Disease/Immunology/Infection Control \nChildren's Hospitals and Clinics of Minnesota \nSt. Paul, MN \nNational Foundation for Infectious Diseases (NFID)\nSCHAFFNER, William, MD \nChairman, Department of Preventive Medicine \nVanderbilt University School of Medicine \nNashville, TN \n40 \n \n   \n  \n  \n   \n  \n \n  \n   \n  \n    \n \n \n   \n   \n   \n  \n  \n \n  \n  \n    \n   \n  \n  \n  \n     \n    \n    \n    \n  \n  \n  \n    \n  \n  \n   \n   \n  \n \n   \n  \n \n  \n  \n   \n  National Foundation for Infectious Diseases (NFID) (alternate) \nDALTON, Marla, PE, CAE \nExecutive Director & CEO \nNational Foundation for Infectious Diseases (NFID) \nBethesda, MD \nNational Medical Association (NMA) \nWHITLEY -WILLIAMS, Patricia, MD Professor and Chair \nUniversity of Medicine and Dentistry of New Jersey Robert Wood \nJohnson Medical School \nNew Brunswick , NJ \nPediatric Infectious Diseases Society (PIDS) \nO’LEARY, Sean, MD, MPH Associate Professor of Pediatrics \nPediatric Infectious Diseases \nGeneral Academic Pediatrics \nChildren’s Hospital Colorado \nUniversity of Colorado School of Medicine \nPediatric Infectious Diseases Society (PIDS) (alternate) \nSAWYER, Mark H, MD Professor of Clinical Pediatrics University of California, San Diego School of Medicine \nSan Diego, CA \nPharmaceutical Research and Manufacturers of America (PhRMA)ROBERT SON, Corey, MD, MPH \nSenior Director, US Medical, Sanofi Pasteur \nSwiftwater, PA \nSociety for Adolescent Health and Medicine (SAHM)\nMIDDLEMAN, Amy B, MD, MSEd, MPH \nProfessor of Pediatrics \nChief, Section of Adolescent Medicine \nUniversity of Oklahoma Health Sciences Center \nOklahoma City, OK \nSociety for Healthcare Epidemiology of America (SHEA)DREES, Marci, MD, MS \nChief Infection Prevention Officer & Hospital Epidemiologist \nChristianaCare Wilmington, DE \nAssociate Professor of Medicine \nSidney Kimmel Medical College at Thomas Jefferson University Philadelphia, PA \n41 \n42  \n  \n \n  \n   \n  \n   \n  \n  \n   \n   \n  \n   \n   \n   \n   \n   \n   \n   \n  \n  \n   \n    \n   \n  \n  \n    \n   \n  \n   \n  \n   \n   \n   \n   \n  \n  \n  \n  \n     \n   \n  \n  \n   \n  \n  \n  \n  \n  ACRONYMS USED IN  THIS  DOCUMENT  \nAAFP American Academy of Family Physicians \nAAP American Academy of Pediatrics \nACA Affordable Care Act \nACHA American College Health Association \nACIP Advisory Committee on Immunization Practices \nACOG American College of Obstetricians and Gynecologists \nACP American College of Physicians \nAE Adverse Event \nAHIP America’s Health Insurance Plans \nAI/AN American Indian/Alaskan Native \nAIM Association of Immunization Managers \nAIRA American Immunization Registry Association \nAMA American Medical Association \nAMDAC Antimicrobial Drug Advisory Committee \nAOA American Osteopathic Association \nAPhA American Pharmacists Association \nAR Adverse Reaction \nARI Acute Respiratory Illness \nASTHO Association of State and Territorial Health Officers \nAUC Area Under the Curve \nBLA Biologics License Application \nCDC Centers for Disease Control and Prevention \nCDER Center for Drug Evaluation and Research \nCDS Clinical Decision Support \nCHD Chronic Heart Disease \nCLD Chronic Lung Disease \nCMS Center for Medicare and Medicaid Services \nCOI Conflict of Interest \nCONUS Continental United States \nCPT Current Procedural Terminology \nCSTE Council of State and Territorial Epidemiologists \nDFO Designated Federal Official \nDoD Department of Defense \nDSMB Data Safety Monitoring Board \nED Emergency Department \nEHRs Electronic Health Records \nEMR Electronic Medical Record \nET Eastern Time \nEtR Evidence to Recommendation \nFAERS FDA Adverse Event Reporting System \nFDA Food and Drug Administration \nGRADE Grading of Recommendation Assessment, Development and Evaluation \nHARMONIE Hospitalized RSV Monoclonal Antibody Prevention \nHCP Healthcare Personnel / Providers \nHHS (Department of) Health and Human Services \n \n    \n  \n   \n   \n   \n  \n   \n     \n   \n    \n      \n   \n   \n   \n   \n   \n     \n  \n   \n   \n    \n   \n  \n  \n  \n   \n    \n   \n   \n   \n   \n  \n  \n  \n  \n   \n   \n  \n  \n  \n   \n  \n   \n  \n   \n  \n  \n   \n   HRSA Health Resources and Services Administration \nICU Intensive Care Unit \nIDSA Infectious Disease Society of America \nIHS Indian Health Service \nIIS Immunization Information System \nIM Intramuscular \nIT Information Technology \nIVIG Intravenous Immunoglobulin Therapy \nLRTD Lower Respiratory Tract Disease \nLRTI Lower Respiratory Tract Illness \nMA-RSV LRTI Medically -Attended RSV Lower Respiratory Tract Infection \nMASO Management Analysis and Services Office \nMELODY Prevention of Medically Attended Lower Respiratory Tract Infection Due to \nRespiratory Syncytial Virus in Healthy Late Preterm and Term Infants \nmAbs Monoclonal Antibodies \nMMWR Morbidity and Mortality Weekly Report \nNACCHO National Association of County and City Health Officials \nNACI National Advisory Committee on Immunization Canada \nNAPNAP National Association of Pediatric Nurse Practitioners \nNCEZID National Center for Emerging and Zoono tic Infectious Diseases \nNCIRD National Center for Immunization and Respiratory Diseases \nNFID National Foundation for Infectious Diseases \nNIAID National Institute of Allergy and Infectious Diseases \nNIH National Institutes of Health \nNMA National Medical Association \nNMD Neuromuscular Disease \nNVAC National Vaccine Advisory Committee \nNVPO National Vaccine Program Office \nNVSN New Vaccine Surveillance Network \nOIDP Office of Infectious Disease and HIV/AIDS Policy \nOTASA Office of Tribal Affairs and Strategic Alliances \nPCP Primary Care Provider/Practitioner \nPCR Polymerase Chain Reaction \nPEP Post-Exposure Prophylaxis \nPHAC Public Health Agency Canada \nPICO Population, Intervention, Comparison, Outcomes \nPIDS Pediatric Infectious Disease Society \nQALY Quality -Adjusted Life Year \nRCT Randomized Controlled Trial \nSAB Spontaneous Abortion \nSAE Serious Adverse Event \nSAHM Society for Adolescent Health and Medicine \nSHEA Society for Healthcare Epidemiology of America \nSME Subject Matter Expert \nUK United Kingdom \nUS United States \nUSG United States Government \nUSVI US Virgin Islands \nVAERS Vaccine Adverse Event Reporting System \n43 \n \n   \n  \n  \n    \n   \n    \n  \n  \n VE Vaccine Efficacy \nVE Vaccine Effectiveness \nVFC Vaccines For Children \nVICP National Vaccine Injury Compensation Program \nVIS Vaccine Information Statement \nVISION Virtual SARS -CoV-2, Influenza, or Other Respiratory Viruses Network \nVSD Vaccine Safety Datalink \nWG Work Group \n44", "summary": "MEETING OF THE ADVISORY  COMMITTEE ON IMMUNIZATION  PRACTICES (ACIP)  AUGUST 3, 2023  MEETING SUMMARY  CONTENTS   THURSDAY: AUGUST 3, 2023 .................................................................................................................... 2  WELCOME AND INTRODUCTIONS ...................................................................................... 2  Call to Order/Roll Call…", "source_url": "https://www.cdc.gov/acip/meetings/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/minutes/summary-2023-08-03-508.pdf", "doc_date": "2023-08-03", "case": "acip", "sub_case": "minutes", "tags": ["acip", "cdc", "vaccines", "minutes"], "page_count": 44}
{"title": "agenda 2023 06 21 23 508", "content": "Final - June 20, 2023\n8:00 Welcome & Introductions Dr. Grace Lee (ACIP Chair)\nDr. Melinda Wharton (ACIP Executive Secretary, CDC)\n8:30 Respiratory Syncytial Virus Vaccines - AdultIntroductionManufacturer presentation: Pfizer season 2 safety & efficacy; \ncoadministration with influenza vaccine\nManufacturer presentation: GSK season 2 safety & efficacy; \ncoadministration with influenza vaccine\nUpdated cost-effectiveness of the Pfizer and GSK vaccines \n(main CDC model)\nComparison of cost effectiveness results of the main CDC \nmodel and each manufacturer model (Pfizer & GSK)\nUpdated EtR (incl. GRADE) and clinical considerations for 2 \nvaccines (Pfizer & GSK)Dr. Camille Kotton (ACIP, WG Chair)\nDr. Alejandra Gurtman (Pfizer)\nDr. Leonard Friedland (GSK)Dr. David Hutton (University of Michigan)Dr. Ismael Ortega Sanchez (CDC/NCIRD)Dr. Michael Melgar (CDC/NCIRD)\n11:45 Break\n12:45 Polio Vaccine\nIntroduction\nRecommendations for Adult Polio VaccinationDr. Oliver Brooks (ACIP, WG Chair)Dr. Sarah Kidd (CDC/NCIRD)\n2:15 Break\n2:30 Influenza Vaccines\nIntroductionWG considerations and proposed recommendations Dr. H. Keipp Talbot (ACIP, WG Chair)Dr. Lisa Grohskopf (CDC/NCIRD)\n4:00 Break\n4:15 Public Comment\n4:35 VOTES \nRSV Adult Vaccines\nPolio VaccineInfluenza Vaccines\nVFC VOTEInfluenza VaccinesDr. Michael Melgar (CDC/NCIRD)Dr. Sarah Kidd (CDC/NCIRD)\nDr. Lisa Grohskopf (CDC/NCIRD)\nDr. Jeanne Santoli (CDC/NCIRD)\n5:30 AdjournMEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)\nCenters for Disease Control and Prevention\nAtlanta, Georgia 30329  \nJune 21-23, 2023\nWednesday, June 21, 2023\nFinal - June 20, 2023\n8:00 Welcome & Introductions Dr. Grace Lee (ACIP Chair)\nDr. Melinda Wharton (ACIP Executive Secretary, CDC)\n8:35 Agency Updates\nCDC, CMS, FDA, HRSA, IHS, OIDP, NIH\n8:55 Pneumococcal VaccinesIntroductionEconomic analysis and public health impact of PCV20 use in \nchildren\nComparison of cost-effectiveness analyses on PCV20 use in \nchildren\nSummary of WG interpretation on EtR and policy optionsDr. Kathy Poehling (ACIP, WG Chair)\nDr. Charles Stoecker (Tulane University)\nDr. Ayabina Diepreye (CDC/NCIRD)Dr. Miwako Kobayashi (CDC/NCIRD)\n10:25 Break\n10:40 Dengue Vaccines\nIntroductionIntroduction of policy questions for TAK-003Cost effectiveness analysis and health impacts of routine \nvaccination with TAK-003 dengue vaccine in Puerto Rico\nSummary of two economic models for dengue vaccine TAK-\n003 use in Puerto Rico​\nPartial EtR framework for TAK-003Dr. Wilbur Chen (ACIP, WG Chair)\nDr. Alfonso Hernandez (CDC/NCEZID)Dr. Guido Espana (University of Notre Dame)\nDr. RajReni Kaul (CDC/NCIRD)\nDr. Joshua Wong (CDC/NCEZID)\n11:40 Break\n12:25 Chikungunya Vaccine\nIntroductionValue of chikungunya vaccine to U.S. travelers and providers\nChikungunya virus infection among laboratory workers \nUpdate on large chikungunya outbreak in ParaguayWorkgroup plans and timelines Dr. Beth Bell (ACIP, WG Chair)Ms. Nicole Lindsey (CDC/NCEZID)\nDr. Susan Hills (CDC/NCEZID)\nDr. Susan Hills (CDC/NCEZID)Dr. Susan Hills (CDC/NCEZID)\n1:25 Break\n1:40 Respiratory Syncytial Virus Vaccines - Pediatric/Maternal\nIntroduction\nEconomic analysis of RSVpreF in pediatric populationsEtR Pfizer maternal RSV vaccineEconomic analysis of combined use of nirsevimab and \nmaternal RSVpreF vaccine\nClinical considerations for RSV maternal vaccine and \nnirsevimabDr. Sarah Long (ACIP, WG Chair)\nDr. David Hutton (University of Michigan)Dr. Katherine Fleming-Dutra (CDC/NCIRD)Dr. David Hutton (University of Michigan) \nDr. Jefferson Jones (CDC, NCIRD)\n4:40 Break\n4:50 Public Comment\n5:10 VOTES \nPneumococcal vaccines\nVFC VOTE\nPneumococcal VaccinesDr. Jeanne Santoli (CDC/NCIRD)\nDr. Jeanne Santoli (CDC/NCIRD)\n5:30 AdjornThursday, June 22, 2023\nFinal - June 20, 2023\n8:00 Welcome & Introductions Dr. Grace Lee (ACIP Chair)\n8:10 Mpox Vaccine\nIntroductionUpdates From the 2022/2023 U.S. Mpox Outbreak:  \nEpidemiology, Vaccine Safety, and Vaccine Effectiveness\nUse of JYNNEOS During Mpox Outbreaks:  Clinical guidance  Dr. Pablo Sanchez (ACIP, WG Chair)\nDr. Faisal Minhaj (CDC/NCEZID)\nDr. Agam Rao (CDC/NCEZID)\nConsiderations for Long-term Protection Against Mpox  Dr. Agam Rao (CDC/NCEZID)\n10:10 Break\n10:20 Meningococcal Vaccines\nIntroductionCost effectiveness analysisGRADE/EtRSummary and workgroup considerationsDr. Kathy Poehling (ACIP, WG Chair)Dr. Ismael Ortega-Sanchez (CDC/NCIRD)Dr. Sam Crowe (CDC/NCIRD)Dr. Sam Crowe (CDC/NCIRD)\n11:35 Break\n11:45 Vaccine SafetyThe childhood immunization schedule and safety: Studies in \nthe Vaccine Safety Datalink\nPreliminary evaluation of aluminum content in childhood \nvaccines and risk of asthma in a Danish nationwide cohortDr. Tom Shimabukuro (CDC/NCEZID)\nDr. Matthew Daley (Kaiser Permanente Colorado)\nDr. Anders Hviid (Statens Serum Institut, Copenhagen, \nDenmark)\n12:30 Break\n12:40 COVID-19 Vaccines \nIntroduction\nUpdates to COVID-19 epidemiology and vaccine effectiveness\nInfection-induced and hybrid immunity\nSummary and work group considerationsDr. Matthew Daley (ACIP WG Chair)\nDr. Fiona Havers (CDC/NCIRD), Dr. Romeo Galang \n(CDC/NCCDPHP), Dr. Ruth Link-Gelles (CDC/NCIRD)\nDr. Jefferson Jones (CDC/NCIRD)\nDr. Megan Wallace (CDC/NCIRD)\n2:40 Adjorn\nAcronyms\nCDC\nCMS Centers for Medicare and Medicaid Services \nCOVID-19 Coronavirus disease 2019\nEtR Evidence to Recommendations Framework\nFDA Food and Drug Administration\nGRADE\nHRSA Health Resources and Services Administration\nIHS Indian Health Service\nNCHHSTP\nNCIRD\nNCEZID\nNIAID\nOIDP Office of Infectious Disease and HIV/AIDS Policy\nSARS-CoV-2 Severe Acute Respiratory Syndrome Coronavirus 2\nWG Work Group\nWHO World Health Organization\nVE Vaccine EffectivenessFriday, June 23, 2023\nNational Institute of Allergy and Infectious DiseasesCenters for Disease Control and Prevention\nGrading of Recommendations Assessment, Development and Evaluation\nNational Center for HIV, Hepatitis, STD and TB Prevention [of CDC/OID] \nNational Center for Immunization & Respiratory Diseases [of CDC/OID] \nNational Center for Emerging and Zoonotic Diseases [of CDC/OID]", "summary": "Final - June 20, 2023 8:00 Welcome & Introductions Dr. Grace Lee (ACIP Chair) Dr. Melinda Wharton (ACIP Executive Secretary, CDC) 8:30 Respiratory Syncytial Virus Vaccines - AdultIntroductionManufacturer presentation: Pfizer season 2 safety & efficacy;  coadministration with influenza vaccine Manufacturer presentation: GSK season 2 safety & efficacy;  coadministration with influenza vaccine Updated cost-effectiveness of the Pfizer and GSK vaccines  (main CDC model) Comparison of cost…", "source_url": "https://www.cdc.gov/acip/meetings/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/agendas/agenda-2023-06-21-23-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "agendas", "tags": ["acip", "cdc", "vaccines", "agendas"], "page_count": 3}
{"title": "summary 2023 06 21 23 508", "content": "MEETING OF THE ADVISORY \nCOMMITTEE ON IMMUNIZATION \nPRACTICES (ACIP) \nJUNE 21 -23, 2023 \nMEETING SUMMARY \nCONTENTS  \nWEDNESDAY: JUNE 21, 2023 .................................................................................................................... 3 \nWELCOME AND INTRODUCTIONS ...................................................................................... 3 \nCall to Order/Roll Call ......................................................................................................... 3 \nAnnouncements .................................................................................................................. 3 \nRESPIRATORY SYNCYTIAL VIRUS VACCINES: ADULT ..................................................... 4 \nBrief Summary .................................................................................................................... 4 \nVote #1: RSV Vaccines for Adults ≥65 Years of Age (Amendment) .................................... 5 \nVote #2: RSV Vaccines for Adults 60─65 Years of Age ...................................................... 6 \nPOLIO VACCINE .................................................................................................................... 6 \nIntroduction ......................................................................................................................... 6 \nRecommendations for Adult Polio Vaccination .................................................................... 7 \nVote #1: Polio Vaccination Unvaccinated and Incompletely Vaccinated Adults ..................16 \nVote #2: Polio Vaccination Unvaccinated and Incompletely Vaccinated Adults ..................17 \nINFLUENZA VACCINE ..........................................................................................................17 \nIntroduction ........................................................................................................................17 \nWG Considerations and Proposed Recommendations .......................................................17 \nVFC Resolution ..................................................................................................................29 \nVote #1: Influenza Vaccination Recommendation ..............................................................31 \nVote #2: Influenza Vaccination MMWR Recommendations and Reports ...........................31 \nVote #3: Influenza Vaccine VFC Resolution .......................................................................32 \nPUBLIC COMMENTS ............................................................................................................32 \nOverview ............................................................................................................................32 \nPublic Comment .................................................................................................................32 \nTHURSDAY: JUNE 22, 2023 ...................................................................................................................... 37 \nAGENCY UPDATES ..............................................................................................................37 \nCenters for Disease Control and Prevention ......................................................................37 \nCenters for Medicare and Medicaid Services .....................................................................38 \nFood and Drug Administration ............................................................................................ 39 \n \n    \n  \n  \n   \n  \n  \n   \n  \n  \n   \n  \n   \n  \n  \n \n   \n  \n  \n  \n  \n  \n   \n  \n  \n  \n  \n  \n  \n  \n  \n   \n   \n   \n \n  Health Resources and Services Administration ..................................................................39 \nIndian Health Service .........................................................................................................40 \nNational Institutes of Health ...............................................................................................40 \nOffice of Infectious Disease and HIV/AIDS Policy ..............................................................41 \nPNEUMOCOCCAL VACCINES .............................................................................................41 \nIntroduction ........................................................................................................................41 \nVote #1: Routine PCV Use for All Children aged <24 Months ............................................42 \nVote #2 : Catch -Up PCV Doses for Children Aged 24–71 Months with an Incomplete PCV \nVaccination Status .............................................................................................................43 \nVote #3: Children Aged 2– 18 Years with Any Risk Condition Who Have Completed Their \nRecommended PCV Doses Before Age 6 Years ................................................................43 \nVote #4: Children Aged 6– 18 Years with Any Risk Condition Who Have Not Received Any \nDose of PCV ......................................................................................................................44 \nVote #5: VFC Resolution ....................................................................................................44 \nDENGUE VACCINE ...............................................................................................................45 \nBrief Summary ...................................................................................................................45 \nCHIKUNGUNYA VACCINE ....................................................................................................45 \nBrief Summary ...................................................................................................................45 \nRESPIRATORY SYNCYTIAL VIRUS VACCINES: PEDIATRIC/MATERNAL .........................45 \nBrief Summary ...................................................................................................................45 \nPUBLIC COMMENTS ............................................................................................................46 \nFRIDAY: JUNE 23, 2023 ............................................................................................................................. 51 \nMPOX VACCINES .................................................................................................................51 \nBrief Summary ...................................................................................................................51 \nMENINGOCOCCAL VACCINES ............................................................................................ 51 \nBrief Summary ...................................................................................................................51 \nVACCINE SAFETY ................................................................................................................51 \nBrief Summary ...................................................................................................................51 \nCOVID -19 VACCINES ...........................................................................................................51 \nBrief Summary ...................................................................................................................51 \nCERTIFICATION ......................................................................................................................................... 53 \nACIP MEMBERSHIP ROSTER .................................................................................................................. 54 \nACRONYMS USED IN THIS DOCUMENT ................................................................................................. 63 \n2 \n \n  \n \n  \n \n  \n \n      \n      \n   \n    \n    \n \n    \n \n \n \n \n     \n      \n \n  \n      \n  \n  \n  \n   \n   \n  \n    \n \n  \n  \n  \n   \n    \n    \n   \n  \n        \n \n    \n   \n   \n  WEDNESDAY : JUNE 21 , 2023  \nWELCOME AND INTRODUCTIONS \nCall to Order/Roll Call \nDr. Grace Lee (ACIP Chair) called to order and presided over the June 21 -23, 2023 Advisory \nCommittee on Immunization Practices (ACIP ) meeting. Dr. Lee co nducted a roll call each day , \nwhich established that a quorum was present. A list of Members, Ex Officios , and Liaison \nRepresentatives is included in the appendixes at the end of this summary document. The \nfollowing conflict s of interest (COIs) were identified : \nDr. Camile Kotton is involved in a clinical trial for Takeda for an investigational antiviral agent \nfor cytomegalovirus (CMV) that does not involve vaccine. \nAnnouncements \nDr. Melinda Wharton (ACIP Executive Secretary, CDC) noted that copies of the slides for the \nmeeting were available on the ACIP website and were made available through a ShareLink ™ \nfile for ACIP Voting, Ex O fficios , and Liaisons Members . The ACIP is, at its heart, a public body. \nEngagement with the public and transparency in all of its processes are vital to the committee’s \nwork. She indicated that there would be 2 oral public comment sessions during this meeting, \nwhich were scheduled for 4:15 Eastern Time ( ET) on June 21, 2023 and 4:50 pm on June 22, \n2023 ET. To create a fair and more efficient process, individuals interested in making an oral \ncomment were asked to submit a request online in advance of the meeting. Priority is given to \nthese advance requests. If more people make requests than can be accommodated, a blind \nlottery is conducted to determine who the speakers will be. Speakers selected in the lottery for this meeting were notified in advance of the meeting. Members of the public also may submit \nwritten comments via https://www.regulations.gov using Docket Number ID CDC- 2023-00 35. \nInformation on the written public comment process, including information on how to make a \ncomment, can be found on the ACIP meeting website. \nAs noted in the ACIP Policies and Procedures manual, ACIP members agree to forgo \nparticipation in certain activities related to vaccines during their tenure on the committee. For \ncertain other interests that potentially enhance a member’s expertise while serving on the \ncommittee , CDC may issue limited COI waivers. Members who conduct vaccine clinical trials or \nserve on data safety monitoring board s (DSMB s) may present to the committee on matters \nrelated to those vaccines, but those members are prohibited from participating in committee \nvotes on issues related to those vaccines. Regarding other vaccines of the concerned company, \na member may participate in discussions with the provision that he/she abstains on all votes \nrelated to that company. ACIP members state any COIs at the beginning of each meeting. \nApplications are being solicited for applications and nominations of candidates to fill upcoming ACIP vac ancies. Detailed instructions for submission of names of potential candidates to serve \nas ACIP members are now available on the ACIP website. The deadline for applications is \nAugust 1, 2023 for the 4 -year terms beginning July 2024. \n3 \n \n   \n \n \n \n    \n    \n     \n    \n    \n    \n      \n  \n      \n  \n \n   \n  \n      \n \n \n   \n \n   \n  \n \n   \n        \n \n \n   \n  \n \n \n      \n     \n      \n   \n  \n    \n      \n  \n     \n   \n   \n \n  \n      \n   \n   \n RESPIRATORY SYNCYTIAL VIRUS VACCINES: ADULT \nBrief Summary \nDuring the RSV session, Dr. Alejandra Gurtman (Pfizer) presented Pfizer data on season 2 \nsafety and efficacy and on co- administration with influenza vaccine. Dr. Leonard Friedland \n(GSK) presented GSK season 2 safety and efficacy and co-administration with influenza \nvaccine. Dr. David Hutton (University of Michigan) presented updated cost -effectiveness of the \nPfizer and GSK vaccines, known as the main CDC model . Dr. Ismael Ortega Sanchez \n(CDC/NCIRD) provided a comparison of cost -effectiveness results of the main CDC model and \neach manufacturer model ( e.g., Pfizer and GSK) . Dr. Michael Melgar (CDC/NCIRD) presented \nthe updated EtR Framework including GRADE (Grading of Recommendation Assessment, \nDevelopment and Evaluation) and clinical considerations for the Pfizer and GSK vaccines. The \nfollowing language was proposed for votes: Vote #1: Adults 65 years of age and older are recommended to receive a single dose of \nRSV vaccine. \nVote #2: Individual adults aged 60─ 64 years may receive a single dose of RSV vaccine, \nusing shared clinical decision- making based on risk assessment. \nDiscussion Points for Clarification Prior to the Vote \nDr. Loehr made a motion to approve the first vote as stated, “Adults 65 years of age and older \nare recommended to receive a single dose of RSV vaccine.” Dr. Brooks seconded the motion. \nDr. Loehr made a motion to approve the second vote with a revision to state, “Individual adults \naged 60─64 years may receive a single dose of RSV vaccine, using shared clinical decision -\nmaking.  Dr. Poehling seconded the motion. \nDr. Sanchez made a motion to amend the first vote to “Adults 65 years and older may receive a \nsingle dose of RSV vaccine using shared clinical decision- making.” Dr. Long seconded the \nmotion. \nDr. Kotton, as the WG Chair, reminded the ACIP members that the WG for people 65 years of \nage and over thought that there was moderate data for desirable anticipated effects, that the \nundesirable anticipated effects were low, and the majority opinion was that the WG favored the \nintervention. The WG spent many months , virtually every week in recent times, reviewing a \nlarge amount of data and research that went into the original proposed vote language. Although they were having an amazing, interesting, and vigorous conversation at this time, she \nsuggested that the members contemplat e that slides 46, 47, 48, and 49 reflected what the WG \nspent time doing rather than perhaps changing opinions now. She also emphasized that along \nwith others, she had major concerns about cost, and thought the companies who make these \nvaccines are beholden to share cost with the ACIP. She personally found it upsetting that GSK virtually doubled the cost of vaccine in recent times and wondered what the future holds. \nFollowin g the public comments and prior to the vote, Dr. Wharton indicated that they heard back \nfrom their colleague at the Center for Medicare and Medicaid Services (CMS), Mary Beth \nHansen, regarding questions the ACIP raised earlier who indicated that should the older adult \nRSV vaccine be recommended by ACIP, coverage would be through Part D for Medicare \nbeneficiaries. \n4 \n \n     \n  \n       \n      \n    \n         \n     \n    \n     \n    \n  \n \n    \n    \n    \n     \n     \n      \n     \n \n   \n      \n      \n    \n     \n   \n    \n    \n    \n \n       \n     \n \n \n      \n \n \n     \n \n     \n    \n \n  \n \n  Dr. Leonard Friedland (GSK) clarif ied that the rationale for the price range review ed during this \nsession and for which the ACIP requested additional information on pricing, the price range \nreviewed reflected AREXVY’s efficacy over 2 full RSV seasons, which resulted in better cost -\neffectiveness versus GSK’s previously submitted analyses. The original price range was bas ed \non clinical data over 1 season only. To aid in the committee’ s decision -making, GSK could \nconfirm that the price of its RSV vaccine would fall within a narrow range of $200 to $295. This \nreflects the totality of the GSK data reviewed earlier concluding that AREXVY provides durable \nefficacy for at least 2 full seasons in the 60 and over population, including in those with \nunderlying comorbidities and across advancing age. This reinforces GSK’s confidence in \nAREXVY’ s potential to make a significant public health impact. The price of AREXVY will be \nbased on cost -effectiveness analys es to ensure efficient allocation of resources. \nDonna Altenpohl (Pfizer) indicated that as was stated earlier in the day, to support the cost-\neffectiveness analyses as part of the US CDC’s EtR framework, Pfizer provided CDC a price \nrange of $180 to $270. Pfizer has been consistent with its price range since they first provided \ntheir cost -effectiveness analyses early this year. According to the CDC cost -effectiveness model \nshared during this session, even at the highest end of the Pfizer range of $270, the Pfizer RSV \nvaccine would have a cost per quality -adjusted life year (QALY) of under $180,000. This is not a \nguarantee, as Pfizer is in the mid st of competitive price negotiations and has not set its list price . \nRegarding a question that arose about reports of 2 possible cases of acute disseminated \nencephalomyelitis (ADEM ) related to RSV vaccines, Dr. James Sejvar (CDC) said that it \nappeared that there was some equating of ADEM with Guillain -Barré Syndrome (GBS). He \nclarified that although both are inflammatory neurologic diseases, GBS and ADEM are \nfundamentally different diseases . Although they can see sporadic cases of ADEM in the setting \nof prior vaccination within the 42-day window, association of causality is sometimes hard to \nestablish. The other point about the 2 cases in question, for the data presented about the RSV \nvaccines , these were preliminary diagnos es of ADEM without the diagnostic testing that \nneurologists would like to see to substantiate a diagnosis. Apparently , these 2 cases were \nbased upon clinical observations only without substantiating neuroimaging or cerebrospinal fluid \ntests. It is difficult, if n ot impossible, to come to a definitive diagnosis of ADEM in the absence of \nconfirmatory neuroimaging or cerebrospinal fluid (CSF) studies. \nDr. Lee reminded everyone that based on the rules of order, the ACIP would first vote on the \namended Vote #1. If it passed, this would be the recommendation. If not, they would return to \nthe original vote. \nVote #1: RSV Vaccines for Adults ≥65 Years of Age (Amendment) \nDr. Lee (ACIP Chair) showed the proposed vote language following the public comment period. \nThe vote was combined with the RSV session for ease of reading: \nAdults 65 years of age and older may receive a single dose of RSV vaccine, using \nshared clinical decision- making. \n5 \n \n  \n \n      \n \n \n       \n   \n \n           \n            \n        \n \n \n     \n \n    \n  \n \n    \n \n \n \n     \n \n \n     \n     \n \n           \n  \n         \n          \n \n \n \n \n \n \n \n   \n \n \n   \n \n \n  \n \n Motion/Vote #1: RSV Vaccines for Adults ≥65 Years of Age (Amendment) \nDr. Poeling made a motion to approve the recommendation as stated, which Dr. Talbot \nseconded. No COIs were declared. The amended motion carried with 10 affirmative votes, 4 \nnegative votes, and 0 abstentions. The disposition of the vote was as follows: \n10 Favored: Bahta, Bell, Cineas, Daley, Lee, Loehr, Long, McNally, Poehling, Sanchez \n4 Opposed: Brooks, Chen, Kotton, Lee, Talbot \n0 Abstained: N/A \nVote #2: RSV Vaccines for Adults 60─65 Years of Age \nDr. Lee (ACIP Chair) showed the proposed vote language following the public comment period. \nThe vote was combined with the RSV session for ease of reading: \nIndividual adults aged 60–64 years may receive a single dose of RSV vaccine, using \nshared clinical decision- making based on risk assessment. \nMotion/Vote #2: RSV Vaccines for Adults 60─65 Years of Age \nDr. Poeling made a motion to approve the recommendation as stated, which Dr. Talbot \nseconded. No COIs were declared. The motion carried with 14 affirmative votes, 0 negative \nvotes, and 1 abstention. The disposition of the vote was as follows: \n14 Favored: Bahta, Bell, Brooks, Chen, Cineas, Daley, Kotton , Lee, Loehr, Long, McNally, \nPoehling, Sanchez \n0 Opposed: N/A \n1 Abstained: Talbot N/A \nPOLIO VACCINE \nIntroduction \nOliver Brooks, MD, FAAP introduced the Polio Vaccination WG, which was formed \napproximately a year ago. The WG’s Terms of Reference (TOR) are to consider the following \npolicy topics under consideration: \n1. Whether more specific guidance on adult vaccination, including use of adult booster doses, \ncan be provided in the context of circulating poliovirus. \n2. Whether adults who are immunocompromised should be recommended an additional adult booster of a polio- containing vaccine. \n6 \n \n      \n  \n \n   \n  \n \n    \n \n \n   \n \n    \n  \n   \n \n    \n  \n   \n   \n    \n \n  \n \n  \n \n \n    \n \n \n    \n \n \n  \n   \n    \n      \n  \n  \n   \n \n \n  \n  \n  \n \n    \n        \n     \n \n \n   3. Whether fractional doses of IPV (fIPV), as prequalified by WHO, should meet polio \nvaccinati on requirements, including for people immigrating to the United States. \n4. Consider criteria under which novel Oral Polio Vaccine type 2 (nOPV2) might be used in \nareas with outbreaks or persistent circulation of poliovirus. \nDuring this session, the WG presented on TOR #1 for the WG’s consideration, deliberation, and \nvote. \nRecommendations for Adult Polio Vaccination \nSarah Kidd, MD, MPH (CDC/NCIRD) presented on behalf of the Polio Vaccination W G, \nindicating that the 2 main objectives for this session were to: 1) summarize the WG’s \ndeliberations on adult polio vaccination specifically for recommendations for unvaccinated and \nincompletely vaccinated adults and recommendations for booster doses of I PV; and 2) present \nthe WG’s proposed language for an ACIP vote. She presented the WG’s deliberations using the \nACIP EtR Framework with the standard domains of: Public Health Problem , Benefits & Harms , \nValues, Acceptability, Resource Use, Equity, and Feasibility. As background, the most recent \nACIP statement on adult polio vaccination was published in 2000, and it contains some \nambiguous and outdated language. The 2000 statement is as follows: \n2000 Recommendations for Inactivated Polio Vaccine (IPV) Vaccination of Adults1 \nVaccination is recommended for certain adults who are at greater risk for exposure to polioviruses than the general population \nUnvaccinated adults who are at increased risk of exposure should receive a primary \nvaccination series with IPV \nAdults who have had a primary series of oral polio vaccine (OPV) or IPV and who are at increased risk of exposure can receive another dose of IPV \nMultiple problems and questions about the recommendations came to light last year when a New York polo paralytic case was identified. First , the 2000 statement focuses almost \nexclusively on adults at increased risk of poliovirus exposure. It was unclear how increased risk \nshould be defined in a setting of circulating vaccine- derived poliovirus (cVDPV) in the US. In \naddition, there was no clear guidance for unvaccinated adults who were not known to be at increased risk of exposure, and there was uncertainty about vaccinated adults and when and if \na booster was advised. With that in mind, the first policy quest ion the WG addressed was as \nfollows: \nPolicy Question #1Should completion of a primary polio vaccination series with IPV be recommended for \nunvaccinated and incompletely vaccinated adults in the US? \nThe population of interest was unvaccinated and incompletely vaccinated US adults (with tOPV \nor IPV) US adults aged ≥18 years . The intervention was completion of a primary vaccination \nseries with IPV. The comparison group was no vaccination or partial series completion. The \nmost important outcomes of in terest were prevention of paralytic poliomyelitis ; serologic \n1 https://www.cdc.gov/mmwr/preview/mmwrhtml/rr4905a1.htm \n7 \n \n      \n     \n   \n \n      \n \n \n \n        \n \n \n \n    \n \n  \n   \n   \n   \n   \n   \n    \n      \n  \n \n   \n    \n     \n \n \n \n \n  \n \n   \n   immunity t o polioviruses Types 1, 2, and 3; SAEs following vaccination; and indirect effects \n(e.g., community transmission and impact on health systems ). The current definition of fully \nvaccinated, an adult is conserved fully vaccinated if they have received the following:2 \nA primary series of at least ≥3 doses of tOPV or IPV in any combination administered ≥4\nw\neeks apar t\nA\nND \nThe last dose in the series was given on or after the 4th birthday\nA\nND \nThe last dose in the series was given ≥6 months after the previous dos e\nI\nn terms of the Public Health Domain, poliovirus infection can cause poliomyelitis and lifelong \nparalysis. Paralytic disease occurs in fewer than 1% of infections , with the exact frequency \nvarying by serotype. Non-paralytic clinical illness occurs in approximately 25%, including 1% – \n5% with aseptic meningitis . Most (75%) poliovirus infections are asymptomatic. The incidence of \nparalytic polio decreased rapidly in the US after introduction of the Salk IPV in 1955, quickly \nfollowed by the Sabin OPV in 1961. The Sabin OPV vaccine was used for routine childhood \nimmunization in the US for decades . In 1997, an enhanced- potency IPV was introduced as part \nof a sequential schedule with IPV followed by OPV. In 2000, the US moved to an IPV -only \nschedule, and IPV has been the only polio vaccine recommended in the US since that time. \nWild-type poliovirus Type 1 (WPV1) and cVDPV are still circulating in certain parts of the world. \nThis map shows the distribution of the almost 700 paralytic polio cases that have been identified \nin the last 12 months (note that environmental detections from wastewater are not shown in this \nmap:3 \n2 https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5830a3.htm \n3 https://polioeradication.org/polio- today/polio- now/ \n8 \n \n     \n   \n   \n    \n     \n    \n   \n    \n  \n   \n    \n     \n  \n \n       \n     \n   \n   \n     \n    \n       \n      \n      \n \n    \n     \n \n  \n     \n    \n    \n   \n     \n    \n \n    \n    \n   \n   \n      \n \n    \n  \n \n    \n       \n     \n   \n  \n       \n      \n  \n    A case of paralytic polio caused by vaccine- derived poliovirus Type 2 (VDPV2 ) was confirmed in \nan unvaccinated young adult from Rockland County, New York in July last year. Genetic \nsequencing has indicated a linkage to polioviruses collected in wastewater in Israel, the UK, and \nCanada. Of note, Rockland County has reported overall low vaccine coverage for over 20 years. \nIn Summer 2022, just 60% of children under age 2 had received 3 doses of IPV. Zip code level \ncoverage was as low as 37% in some areas. Fortu nately, no additional paralytic cases have \nbeen identified. Poliovirus related to the case was detected in wastewater in several other New \nYork counties and New York City. Retrospective testing detected poliovirus in the area as early \nas April 2022, indicating circulating and asymptomatic infections in the area at least since that \ntime. Related virus continued to consistently be detected in wastewater until the beginning of \nNovember of last year. Only 2 samples have been positive for poliovirus since November  1st, \nwith the most recent being collected on February 22nd in Rockland County. Samples collected in \nthe last 15 weeks all have been negative. \nLooking at the pattern of wastewater detections in each affected county by week, there was just \none paralytic polio case identified. But the presence of that case and the pattern of wastewater \ndetections indicate that there were likely at least 1,000 to 2,000 mostly asymptomatic infections \nin the area. Circulating poliovirus poses a risk of paralytic polio to those who do not have immunity . In the US, most people are protected from paralytic polio because they have been \nvaccinated. National Salk IPV vaccination campaigns in the late 1950s targeted all persons up to 40 years of age . In terms N ational US Im munization Survey (USIS) data\n4 for Salk IPV \nvaccination coverage by September 1961 by age and race, campaign coverage was highest \namong children 5─14 years of age in 1961. This would be birth years 1947─ 1956. Also of note, \nestimates of coverage were higher among whites than non- whites in all age groups. In \ncomparison to children and adolescents, coverage was lower in adults ≥20 years of age. Not \nmany adults ≥40 years of age were vaccinated in the campaigns. \nAfter that USIS household survey, subsequent surveys focused on coverage among preschool -\naged children.5 It is important to note that data from 3 different national surveys for 3-dose polio \nvaccination coverage among children used different methodologies and have different \nlimitations. The USIS was based on parental recall and is thought to underestimate actual \ncoverage by as much as 20% when compared to actual vaccination records. In contrast, the \nNational Immunization Survey (NIS) data, come from actual vaccination records. Wh ile \ncoverage levels, especially in the 1970s and 1980s , might be cause for concern. \nIt is interesting to contrast those coverage data with serosurveys that indicate that a large \nmajority of Americans have protective antibodies to poliovirus. In a National Health and Nutrition \nExamination Survey (NHANES) survey conducted in 2009─ 2010,6 seroprevalence varied by \npoliovirus serotype but was high in all the age groups studied. Seroprevalence for Type 3 was \nconsistently the lowest but remained high even in the oldest age group. Of note, there were \nsome small differences in seropositivity by race ethnicity group, but none of these were \nstatistically significant among the younger age groups. Among older adults, differences by race \nand ethnicity generally were not statistically significant with a few exceptions where Mexican -\n4 Morris, Public Health Reports 1964 \n5 Sources: Simpson et al, AJPM 2001 Forty years and four surveys: How does our measuring measure up? – ScienceDirect. CDC, \nMMWR 2001 National, State, and Urban Area Vaccination Coverage Levels Among Children Aged 19-- 35 Months ---United \nStates, 2000 (cdc.gov). CDC, MMWR 2006 National, State, and Urban Area Vaccination Coverage Among Children Aged 19--35 \nMonths ---United States, 2005 (cdc.gov). CDC, MMWR 2011 National and State Vaccination Coverage Among Children Aged 19--\n35 Months ---United States, 2010 (cdc.gov). Hill et al, MMWR 2016 Vaccination Coverage Among Children Aged 19– 35 Months — \nUnited States, 2015 | MMWR (cdc.gov). Hill et al, MMWR 2018 Vaccination Coverage Among Children Aged 19–35 Months — \nUnited States, 2017 | MMWR (cdc.gov). \n6 Wallace et al, BMC Public Health 2016 \n9 \n \n  \n       \n     \n       \n      \n \n     \n  \n    \n   \n   \n \n   \n    \n    \n   \n     \n     \n       \n    \n  \n \n    \n     \n   \n   \n     \n   \n   \n       \n  \n \n      \n   \n    \n  \n   \n    \n   \n   \n  \n    \n     \n   \n   \n \n        \n           \n \n        \n \n  American adults had slightly lower seroprevalence of Type 2 antibodies compared to non-\nHispanic Blacks in those 20─ 39 years of age and compared to non- Hispanic Whites in \nindividuals 40─ 49 years of age . They also had lower levels of Type 3 antibodies compared to \nnon-Hispanic Whites in individuals 40─ 49 years of age. Unfortunately, there are no \nseroprevalence data for older age groups by race and ethnicity. \nTo summarize the problem, the US remains at risk of poliovirus importations as long as there is \nongoing transmission of poliovirus globally. Data indicate that most US adults have serologic immunity to polioviruses Type 1, 2, and 3. However, unvaccinated and incompletely vaccinated \nadults remain susceptible to paralytic polio if exposed to poliovirus. In response to the question for the E tR domain , the WG agreed that paralytic polio is a problem of public health importance . \nRegarding the Benefits and Harms domain, the effectiveness of enhanced -potency IPV has \nbeen established. The presence of detectable neutralizing antibodies is an accepted correlative \nprotection against paralytic disease. However, immunity against paralytic disease can be present even in the absence of detectable antibodies. Studies of serologic immunogenicity \namong infants and children show that 70% to 100% are seropositive after 2 IPV doses and 88% \nto 100% are seropositive after 3 doses. There are limited data on VE against paralytic polio, but \nestimates range from 36 % to 89% for 1 dose and 89% to 98% for 2 doses. However, because \nthis is a routine childhood vaccine, there is a paucity of data for previously unvaccinated adults \nwho receive a primary series.\n7 \nIn addition to serologic immunity, which protects against severe disease and paralysis, it also \nimportant to consider mucosal immunity and the potential effect of IPV on transmission. IPV \ndoes not decrease the proportion of people who will shed poliovirus when exposed. Multiple \nstudies have shown that there is no significant difference between IPV and unvaccinated \nindividuals in terms of the odds of shedding. However, several studies indicate that IPV may \nreduce the quantity and perhaps duration of shedding. Although a recent modeling study \nindicated no impact of IPV. There are fewer data on nasopharyngeal immunity following IPV, but \ndata from 2 studies suggest that rates of nasopharyngeal shedding are similar and low at 0% to \n4% among both OPV and IPV vaccinees.8 \nThe safety of IPV also is well- established and IPV is well -tolerated. Local reactions at the \ninjection site were reported during clinical trials and up to a third reported erythema, induration, or tenderness at the injection site. Combining IPV with other vaccines has not been associated \nwith increased frequency or severity of reported AEs, compared to when the other vaccines are \nadministered alone. No SAEs have been causally associated with the use of the current \nformulation of IPV.\n9 In a paper that looked at 2000 ─2012 data from VAERS during a period \nwhen more than 250 million IPV doses were distributed during 2000- 2012, 41,792 AEs were \nsubmitted for IPV -containing vaccines. Most of these were non- serious and 95% were among \npersons less than 7 years of age. Most events were associated with IPV that was co \nadministered with other vaccines and standalone IPV accounted for just 0.5% of reports.10 It is \nimportant to remember that VAERS is a passive reporting system cannot assess causal \nassociations between vaccination and AEs . However, the lack of a signal in VAERS after \ndecades of IPV use is reassuring. \n7 Vidor et al review, PIDJ 1997. Stoeckel et al, Rev Infect Dis 1984. CDC, MMWR 1988. John, Rev Med Virol 1993. \n8 Hird and Grassly meta- analysis, PLoS Pathogens 2012. Kok et al, Bulletin of WHO 1992. Onorato et al, JID 1991. Brouwer et al, J \nR Soc Interface 2022. \n9 : Sanofi Pasteur Package Insert -IPOL (fda.gov) . Vidor et al, PIDJ 1997. Murdin et al, Vaccine 1996. Wattigney et al, Pediatrics \n2001. IOM 1994. \n10 Iqbal et al, Lancet ID 2015. \n10 \n \n  \n      \n   \n  \n  \n \n \n     \n       \n   \n   \n   \n    \n      \n    \n   \n  \n    \n     \n    \n    \n \n    \n      \n   \n    \n    \n \n   \n   \n     \n       \n   \n  \n \n    \n    \n    \n    \n    \n      \n   \n  \n     \n  \n  \n \n   For the E rR domain of Benefits and Harms, the WG interpretation was that taking into account \nboth the individual -and population- level effects, the desirable anticipated effects of completing a \npolio vaccination series are large , the undesirable anticipated effects are minimal, and the \nanticipated benefits of co mpleting a primary polio vaccination series outweigh the anticipated \nharms. \nIn terms of the Values domain, an Annenberg Science Knowledge (ASK) survey11 was \nconducted in October 2022 that included questions about polio, so there are some data about \nwhat the general public thinks about polio recently. In this survey, 59% of people said it would \nbe “extremely bad ” to have polio and an additional 26% said it would be “very bad ” to have \npolio. This was a higher proportion of the population than for other diseases surveyed, including \nlong- COVID, Mpox, or measles. There is evidence that the general public values polio \nprevention, at least at the individual level. In addition, 85% of respondents said that they were \nlikely to recommend that an eligible person in their household get vaccinated with the polio \nvaccine, indicating relatively high acceptability of the vaccine among the general public. \nHowever, when thinking about the values of the specific population in question, unvaccinated or \nincompletely vaccinated adults, it is likely that this is a heterogeneous group that consists of \npersons whose family chose for them to not be vaccinated as children and persons who missed \nopportunities to be vaccinated as children. There is a lack of data on how these populations \ncurrently perceive their risk of paralytic polio and how they perceive the anticipated positive \nversus negative effects of polio vaccination. Additional acceptability considerations include the \npros that the context of global polio eradication effor ts and the prevention of paralytic polio have \nbeen a public health priority for decades. In practice, there currently are many competing \npriorities for clinicians and local public health departments. The cons are competing priorities for \nclinicians and local public health departments and uncertainty about eligibility for vaccination \nand the true level of risk to adults in the US also could undermine acceptability . \nThe WG thought that whether the target population of unvaccinated or incompletely vaccinated \nadults feel that the described effects of vaccination are large relative to the undesirable effects \nlikely varies because of the heterogeneity of this group. The WG also felt that there is probably \nimportant uncertainty or variability in the val ues of the target population. In contrast, for \nacceptability of key stakeholders overall, the WG felt that providing a primary series to \nunvaccinated or incompletely vaccinated adult was probably acceptable to key stakeholders. \nMoving to the Feasibility domain, there currently is just one US -licensed manufacturer of \nstandalone IPV (e.g., Sanofi). There are 3 US -licensed manufacturers of combination vaccines \nthat include IPV (e.g., Sanofi, Merck, GSK). However, these combination vaccines are currently \nnot indicated for adults. The potential demand for IPV is difficult to quantify. There are no data \non the number of adults who know they are unvaccinated or incompletely vaccinated, so it is \ndifficult to quantify potential demand. In practice, it is possible to learn from New York ’s \nexperience last summer. New York State and New York City did not experience any significant \nIPV supply issues despite identification of a polio case, persistent wastewater detections in the \narea, national media attention and calls , and a concerted effort by the health department to \nvaccinate unvaccinated persons, including adults. \n11 https://www.annenbergpublicpolicycenter.org/what -u-s-adults -know -and-believe- about -polio- and-the-bivalent -covid -booster/ \n11 \n \n    \n      \n    \n   \n  \n     \n    \n  \n  \n  \n \n    \n   \n  \n   \n     \n   \n \n \n    \n     \n \n     \n \n     \n  \n \n    \n  \n    \n  \n  \n     \n  \n  \n     \n   \n   \n    \n     \n  \n \n \n \n  \n   \n   \n  \n   \n    \n   Other resource and feasibility considerations include issues with access. Adult medicine offices \ntypically do not stock IPV, so access to vaccination sites that do stock IPV could be a barrier to \nimplementation. Also, there are concerns about the potential effects on health systems and their \nvaccine screening and patient recall algorithms. However, the WG felt that these concerns could \nbe mitigated with clear guidance for who is eligible for vaccination with these recommendations. \nThe WG talked at length about the feasibility of implementing risk -based recommendations, \nparticularly if risk of exposure in the population changes over time. Overall, the WG felt that \nvaccination of adults who are known or suspected to be unvaccinated or incompletely \nvaccinated was probably or was a reasonable and efficient allocation of resources. They also \nfelt that it was probably feasible to implement . \nFor the Equity domain, there are different rates of childhood vaccination and poliovirus immunity \nin different communities . Having an opportunity to receive catch -up polio vaccination as an adult \nlikely increases equity. There are no known differences in VE among immunoc ompetent \npersons in the US setting. A ssuring equitable access to vaccination sites with IPV will be an \nimportant consideration for implementation. Overall, the WG felt that providing polio vaccination \nfor adults known or suspected to be unvaccinated or incompletely vaccinated probably would \nincrease equity. \nFor the overall balance of consequences, taking into account all of the E tR domains just \npresented, the WG considered 2 different populations of unvaccinated adults. For unvaccinated \nand incompletely vaccinated adults known to be at increased risk of poliovirus exposure, the \nWG’s judgment was that the desirable consequences clearly outweigh undesirable \nconsequences in both settings. For unvaccinated and incompletely vaccinated adults who are \nnot specifically known to be at increased risk of poliovirus exposure, the WG’s judgement was \nthat desirable consequences probably outweigh undesirable consequences in most settings. Most of the WG’s deliberations focused on whether the recommendations for unvaccinated \nadults should be a risk -based recommendation or a uniform recommendation for all \nunvaccinated adults. Currently , situations that are considered to put adults at increased risk of \npoliovirus  exposure include international travelers, laboratory and healthcare workers, and \nhealthcare workers or other caregivers. In addition, unvaccinated or incompletely vaccinated \nadults whose children will be receiving an OPV and unvaccinated adults or incompletely \nvaccinated adults who are living or working in a community where poliovirus is circulating are \nconsidered to be at increased risk of exposure and vaccine is recommended. It became clear to \nthe WG that most of these situations pose risk at the individual level and there would be an \nopportunity to anticipate the risk and vaccinate prior to the potential exposure. A situation for \nunvaccinated and incompletely vaccinated adults in a community where poliovirus is circulat ing \nwas different. The situation affects an entire population, and the community already is at \nincreased risk at the time the risk is recognized. This means there potentially would be missed \nopportunities for vaccination prior to exposure if the recommendation remains solely a risk-\nbased recommendation. \nAdditional challenges with the current risk -based recommendation came to light in 2022 when \nCDC, New York City , and state health departments received numerous questions about which \nadults were at increased risk of exposure. For instance, in which of these counties with \nwastewater detections or adjacent to wastewater detections are unvaccinated adults considered \nat increased risk of exposure? Are counties with a single wastewater detection of poliovirus \nconsi dered to be at increased risk of exposure? When are unvaccinated adults in these counties \nno longer at increased risk of exposure? Are unvaccinated adults traveling to these counties at \nincreased risk of exposure? As wastewater surveillance becomes more co mmon, it is possible \n12 \n \n   \n    \n \n \n     \n     \n   \n    \n     \n     \n     \n    \n  \n   \n     \n \n \n        \n \n    \n   \n \n \n  \n \n  \n \n  \n    \n \n   \n    \n \n \n \n  \n   \n  \n \n     \n \n     \n       \n    \n    \n     \n  \n \n    that other jurisdictions might experience sporadic detections of poliovirus in their wastewater . \nThese are the types of challenges that arise when trying to implement a risk -based \nrecommendation. \nWith these factors in mind, the pros o f a uniform recommendation are that it allows \nunvaccinated adults and their healthcare providers to take advantage of opportunities to get \nvaccinated before they are at increased risk of exposure. It also brings adult polio vaccination \npolicy closer in line with other routine childhood vaccines such as MMR and varicella vaccines. \nIt is a less complicated policy to communicate , understand , and implement in that the \nrecommendation does not change based on the latest wastewater data. The cons are that most \nadults  in the US still have a low risk of poliovirus exposure and paralytic polio and most adults \nreceived their primary polio vaccination series as children. Another other con is that demand for \nIPV potentially could exceed supply, particularly if a large number of adults without \ndocumentation of polio vaccination status were to assume that they were not vaccinated. \nHowever, the WG felt that this issue could be mitigated by providing guidance for this group in \nthe clinical considerations. \nUltimately, the majority of the WG supported a uniform recommendation. However , a substantial \nminority favor ed the current risk -based recommendation with the addition of language \nspecifically addressing unvaccinated adults who are not know n to be at increased risk of \nexposure. The proposed recommendation language and important Clinical Considerations \nfollow: \nProposed Language for Policy Question #1 \nAdults who are known or suspected to be unvaccinated or incompletely vaccinated against polio \nshould complete a primary vaccination series with IPV. \nImportant Context to Be Included in Clinical Considerations\nIn general, unless there are specific reasons to believe they were not vaccinated, most adults \nwho were born and raised in the United States can assume they were vaccinated against polio \nas children. Polio vaccination has been part of the routine childhood immunization schedule for \ndecades and is still part of the routine childhood immunization schedule. Adults who received \nany childhood vaccines almost certainly were vaccinated for polio. \nThe second policy question addressed by the WG was as follows: \nPolicy Question #2Should a booster IPV dose be recommended for adults at increased risk of poliovirus exposure who have previously completed a primary polio vaccination series? \nThe specific population being considered was US adults ≥18 years if age who are at increased \nrisk of poliovirus exposure who have also completed a primary polio vaccination series with trivalent OPV, IPV, or a combination of both. The intervention was a booster dose of IPV and \nthe comparison group was adults who competed a primary series, but did not receive a booster \ndose. Again, the main outcomes of interest were : prevention of paralytic polio; serologic \nimmunity to poliovirus Types 1, 2, and 3; SAEs following vaccination; and indirect effects (e.g., \ncommunity transmission and impact on health systems. The 2000 booster statement follows:\n12 \n12 CDC MMWR 1977; CDC MMWR 1986 \n13 \n \n  \n \n    \n    \n   \n \n    \n    \n      \n \n   \n  \n  \n \n    \n   \n     \n      \n   \n  \n   \n \n \n \n     \n  \n \n  \n \n     \n      \n      \n  \n  \n \n  \n     \n   \n      \n    \n  \n \n     \n    \n      \n      \n           \n  2000 Statement \nAdults who have had a primary series of OPV or IPV and who are at increased risk [of \nexposure to poliovirus ] can receive another dose of IPV. Available data do not indicate \nthe need for more than a single lifetime booster dose with IPV for adults. \nIn terms of the rationale, this has been a long- standing recommendation since tOPV was used \nin routine immunization. However , the actual need for a supplementary dose has not been \nestablished. It has been thought that “there is value in assuring protection against infection with \nwild polioviruses when exposure can reasonably be expected. ” (1977 ACIP Statement). Of note, \nthere were at least 2 reported cases of paralytic polio in adult travelers who had completed a \nprimary series with Salk IPV and/or tOPV. However , further details on these cases are not \navailable and it is unknown whether a booster dose would have prevented these cases. \nThe 2000 guidance was complicated in 2014 when CDC issued interim guidance in response to \nnew WHO Polio International Health Regulations (IHR) Emergency Committee Temporary \nRecommendations . The WHO recommendations were for travelers who were departing \ncountries with poliovirus circulation in order to prevent exportation. They applied to residents \nand travelers who were staying in the country for more than 4 weeks. If implemented by a \ncountry, proof of polio vaccination (IPV or tOPV) within the last 12 months could be required \nprior to leaving the country . This recommendation or a similar recommendation is still included \nin the most recent polio IHR statement. In response to this new WHO recommendation in 2014, \nwhich differed from ACIP recommendations, CDC published interim guidance in 2014 that \nstated :13 \n“Adults who have completed a routine series of polio vaccine are considered to have lifelong immunity to poliovirus but da ta are lacking. As a precaution, persons aged ≥18 \nyears who are traveling to areas where there has been WPV circulation in the last 12 months and who have received a routine series with either IPV or OPV in childhood should receive another dose of IPV before departure. For adults, available data do not \nindicate the need for more than a single lifetime booster dose with IPV.” \nIt is unclear whether previously vaccinated adults need an IPV booster for protection. Results \nfrom the NHANES serosurvey show ed that seroprevalence of neutralizing antibodies were high \nfor all 3 serotypes and in all age groups studied.\n14 There are no data on the comparative VE of \na primary series plus booster compared to a primary series alone, but serologic studies in adults \nwith heterogeneous pre- booster vaccination histories and heterogeneous seropositivity have \nshown that 98 % to 100% are seropositive 1 month after receiving an IPV -containing booster. \nOne study also followed up trial participants 10 years later and 98% to 100% w ere still \nseropositive at that time.15 In terms of the safety of IPV, combining IPV with other vaccines has \nnot been associated with increased frequency or severity of reported adverse reactions compared to when other vaccines are administered alone, and no SAEs have been causally \nassociated with the current formulation of IPV.\n16 \n13 Wallace MMWR 2014; Statement of the thirty -fifth Polio IHR Emergency Committee (who.int) \n14 Wallace et al, BMC Public Health 2016 \n15 Sources: Broderick et al, Vaccine 2015; Domenicus et al, Vaccine 2014; Fukushima et al, Vaccines 2022; Grimprel et al, Vaccine \n2005; Kovac et al, Vaccine 2015; Larnaudie et al, Human Vaccines 2010; Zimmermann et al, Vaccine 2013. \n16 Sources: Sanofi Pasteur Package Insert -IPOL (fda.gov) . Vidor et al, PIDJ 1997. Murdin et al, Vaccine 1996. Wattigney et al, \nPediatrics 2001. IOM 1994. \n14 \n \n        \n    \n \n \n \n       \n    \n   \n \n \n      \n    \n \n    \n       \n \n \n     \n     \n   \n   \n    \n  \n   \n    \n \n \n     \n      \n  \n \n  \n   \n     \n  \n     \n     \n \n \n      \n   \n  \n      \n     \n \n \n  For the E tR domain of Benefits and Harms, the WG determined that for adults at increased risk \nof exposure, the desirable anticipated effects of receiving an IPV booster were smal l to \nmoderate,  the undesirable effects were minimal, and the anticipated benefits outweighed the \nanticipated harms. \nConsidering target population values, the results of that ASK survey conducted in 2022 showed \nthe majority of adults surveyed thought that having polio would be “ extremely bad” or “very bad ” \nand that 85% said they were likely to recommend that someone in their household get \nvaccinated against polio if they were eligible. In terms of the Value domain, the WG thought that the target population, meaning previously \nvaccinated adults who were at increased risk of exposure, probably felt that the desirable effects \nof a booster were large compared to the undesirable effects. However, this was split with a \nsignificant portion of the WG also saying that they did not know based on the limited data \navailable. The WG thought there probably was not important uncertainty or variability in terms of \ntarget population values. \nWhen considering acceptability, feasibility , and resources for IPV bo osters, the WG noted that \nthe current recommendation that adults who have had a primary series of OPV or IPV and who \nare at increased risk of exposure to poliovirus can receive another dose of IPV , that this \nrecommendation is long- standing, and it is generally considered accepted and feasible. \nHowever , if the at increased risk of exposure group were to be expanded, for instance to include \npreviously vaccinated adults in certain US areas with poliovirus circulation, f easibility might be \naffected in the future. Again, the experience of New York State and New York City in 2022 is \nhelpful in that even in the context of a polio case and media attention, IPV supply was not a \nsignificant issue. \nThe WG agreed that providing a booster IPV dose to adults at increased risk of exposure \n“probably ” is or “is” acceptable to key stakeholders , “probably ” is a reasonable and efficient \nallocation of resources , and “probably” or “is” feasible to implement. \nTo address the E quity E tR domain, there are no known differences in res ponse to a primary \nseries or need for a booster by socioeconomic group in the US setting. No groups or settings \nare known to be disadvantaged by the current recommendation. However, the WG thought that \nthere is a potential for increased equity by boosting immunity in persons at increased risk of exposure, especially persons with potential occupational exposures to poliovirus. On that basis, \nthe WG thought that boosters for those at increased risk of exposure “probably ” would result in \nincreased equity. \nFor the overall WG judgment, taking into account all of the E tR domains, the WG thought the \ndesirable consequences of an IPV booster probably outweigh the undesirable consequences in \nmost settings for previously vaccinated adults who are at increased risk of poliovirus exposure. \nThe majority of the WG agreed with the current ACIP recommendation for adult boosters and \nrecommended a vote to reaffirm this language. This recommendation is risk -based and based \non shared clinical decision- maki ng, and the proposed language includes some slight evidence \nto modernize the language compared to the 2000 statement. \n15 \n \n   \n    \n   \n    \n \n \n  \n \n   \n \n   \n \n   \n \n \n    \n \n    \n   \n \n \n      \n \n \n   \n        \n      \n    \n    \n \n \n  \n \n  \n    \n   \n \n          \n   \n         \n        \n \n  Proposed Language for Policy Question #1 \nAdults who have received a primary series of tIPV or OPV in any combination and who are at \nincreased risk of poliovirus exposure may receive another dose of IPV. Available data do not \nindicate the need for more than a single lifetime booster dose with IPV for adults. \nClinical Considerations \nSituations that put adults at increased risk of poliovirus exposure include: \nTravelers who are going to countries where polio is epidemic or endemic (For additional \ninformation, see Polio: For Travelers). \nLaboratory and healthcare workers who handle specimens that might contain \npolioviruses. \nHealthcare workers or other caregivers who have close contact with a person who could \nbe infected with poliovirus. \nVote #1: Polio Vaccination Unvaccinated and Incompletely Vaccinated Adults \nSarah Kidd, MD, MPH (CDC/NCIRD) displayed and read the proposed vote language following \nthe public comment period. The vote was combined with the Polio Vaccine session for ease of \nreading: \nAdults (aged ≥18 years) who are known or suspected to be unvaccinated or \nincompletely vaccinated against polio should complete a primary vaccination series with \nIPV. \nImportant Context to Be Included in Clinical Considerations: \nIn general, unless there are specific reasons to believe they were not vaccinated, most adults who were born and raised \nin the United States can assume they were vaccinated against polio as children. Polio vaccination has been part of the \nroutine childhood immunization schedule for decades and is still part of the routine childhood immunization schedule. Adults who received any childhood vaccines almost certainly were vaccinated for polio. \nMotion/Vote #1 : Adult Polio Vaccination \nDr. Poeling made a motion to approve the recommendation as stated, which Dr. Talbot \nseconded. No COIs were declared. The motion carried with 14 affirmative votes, 0 negative \nvotes, and 0 abstentions. The disposition of the vote was as follows: \n14 Favored: Bahta, Bell, Brooks, Chen, Cineas, Daley, Kotton, Lee, Loehr, Long, McNally, \nPoehling, Sanchez, Talbot \n0 Opposed: N/A \n0 Abstained: N/A \n16 \n \n    \n \n    \n  \n \n \n    \n    \n     \n \n \n \n   \n \n \n    \n  \n \n          \n   \n         \n        \n \n \n \n \n \n \n \n   \n \n  \n   \n \n  \n \n \n \n     \n \n   \n        \n   \n   \n  \n     \n  \n \n  \n  \n   Vote #2: Polio Vaccination Unvaccinated and Incompletely Vaccinated Adults \nSarah Kidd, MD, MPH (CDC/NCIRD) displayed and read the proposed vote language following \nthe public comment period. The vote was combined with the Polio Vaccine session for ease of \nreading: \nAdults who have received a primary series of tIPV or OPV in any combination and who \nare at increased risk of poliovirus exposure may receive another dose of IPV. Available \ndata do not indicate the need for more than a single lifetime booster dose with IPV for \nadults. \nMotion/Vote #2: Adult Polio Vaccination \nDr. Poeling made a motion to approve the recommendation as stated, which Dr. Cineas seconded. No COIs were declared. The motion carried with 14 affirmative votes, 0 negative \nvotes, and 0 abstentions. The disposition of the vote was as follows: \n14 Favored: Bahta, Bell, Brooks, Chen, Cineas, Daley, Kotton, Lee, Loehr, Long, McNally, \nPoehling, Sanchez, Talbot \n0 Opposed: N/A \n0 Abstained: N/A \nINFLUENZA VACCINE \nIntroduction \nH. Keipp Talbot, MD, MPH (ACIP, WG Chair) reported that recent WG activities have included \npreparation of the proposed 2023- 2024 Influenza Statement and discussion of the safety of \ninfluenza vaccination of persons with egg allergy. She indicated that this session would include \npresentations focused on influenza vaccination of persons with egg allergy, including: 1) \nBackground, WG Considerations, and an EtR Framework Discussion; and 2) Proposed recommendations for the 2023- 24 influenza season. \nWG Considerations and P roposed Recommendations \nLisa Grohskopf MD, MPH (CDC/NCIRD) presented the EtR discussion and WG considerations \nfor influenza vaccination of persons with e gg allergy , particularly those with a history of severe \nallergic reaction to egg. Beginning with some background , egg allergy is a relatively common \nfood allergy affecting approximately 1% to 3% of children by 3 years of age.\n17 It resolves for \nmany during later childhood and adolescence . In one study , 68% have developed a tolerance \nby 16 years of age.18 Reactions r ange from mild to life -threatening. Diagnosis is generally done \nby a clear history of immediate allergic reactions to egg or egg -containing foods, as well as skin \nprick testing (SPT) or estimation of egg -specific I gE levels.19 Of the 9 influenza vaccines that \nare currently available in the US, 7 are produced through the propagation of viruses in \n17 Eggesbo M et al. Allergy 2001;56(5):403- 411; and Erlewyn- Lajeunesse M et al. BMJ 2009;339:b3680 \n18 Savage JH et al. J Allergy Clin Immunol 2007;120(6):1413-7 \n19 Egges bo M et al. Allergy 2001;56(5):403- 411 \n17 \n \n     \n      \n       \n    \n    \n     \n  \n \n     \n   \n    \n   \n     \n \n    \n \n \n \n    \n       \n   \n   \n       \n   \n    \n    \n   \n   \n    \n       \n \n  \n  \n \n \n \n    \n     \n    \n  \n   \n \n  \n        \n \n        \n \n     \n    embryonated eggs. These vaccines can and generally do contain residual amounts of egg \nproteins (e.g., ovalbumin) . For 5 of the 7 egg-based vaccines, the egg ovalbumin content is \nlisted in the package insert and is generally low, under about 1 mcg/dose . For 2 of the 7 egg-\nbased vaccines, ovalbumin is not listed . There are 2 egg-free vaccines, Flucelvax Quadrivalent, \nwhich is a cell culture -based inactivated vaccine (ccIIV4 ), and Flublok Quadrivalent. While t hese \n2 vaccines are considered egg- free, only Flucelvax Quadrivalent is approved for children <18 \nyears of age . \nACIP currently recommends ,20 and has for a number of years , that all persons with egg allergies \nshould receive influenza vaccine and that it is not necessary to receive an egg- free vaccine. Any \ninfluenza vaccine that is otherwise appropriate for the person’ s age and health status can be \nused (i.e., any IIV4, RIV4, or LAIV4) . For those who have a history of severe allergic reaction to \negg, and for the purposes of the ACIP guidance, this is defined as follows : \n“If a vaccine other than ccIIV4 or RIV4 is used, the selected vaccine should be \nadministered in an inpatient or outpatient medical setting, including but not necessarily \nlimited to hospitals, clinics, health departments, and physician offices. Vaccine \nadministration should be supervised by a health care provider who is able to recognize and manage severe allergic reactions.” \nNo specific post -vaccination observation period is recommended . The primary focus of this \nsession concerned the language pertaining to severe allergic reaction in terms of whether this \nadditional recommendation no longer needs to be made for people with severe egg allergy. \nSome of the reasoning behind this has to do with guidance from other professional \norganizations. The recommendations of the J oint Task Force (JTF) of the American Academy of \nAsthma, Allergy & Immunology and the American College of Asthma, Allergy & Immunology (Joint Task Force AAAAI/ACAAI ) differ from the ACIP and American Academy of Pediatrics \n(AAP) recommendations. Since the 2016 -2017 season, AAP has recommended no additional \nmeasures for persons with egg allergy.\n21 The AAP 2022- 2023 Influenza Prevention and Control \nGuidance states that “Children with egg allergy can receive any influenza vaccine without any \nadditional precautions beyond those recommended for all vaccines. ”22 The Technical Report \nthat accompanies the recommendations indicates that measures such as the use of specific \nvaccines, observation periods, or restricting vaccination to specific medical settings and \nscreening for egg allergy are not warranted and constitute a barrier to vaccination.23 The \nAAAAI /ACAAI  similarly state that , “No special precautions beyond those recommended for the \nadministration of any vaccine to any patient are necessary for administration of influenza \nvaccine to egg- allergic individuals.”24 \nSevere allergic reactions to vaccines overall are uncommon and anaphylaxis is rare, but given their potential seriousness, preparation for such reactions is recommended when administering \nany vaccine to any recipient. The General Best Practices G uidelines for Immunization in the \nchapt er entitled “Managing Adverse Reactions ” notes that allergic reactions are uncommon, and \nanaphylaxis following vaccines is rare , but also notes that vaccination settings should be \nprepared for potential serious reactions, noting that epinephrine and equipm ent for managing \n20 CDC/ACIP. MMWR Recomm Rep 2022;71(No. RR- 1):1–28 \n21 Recommendations for Prevention and Control of Influenza in Children, 2016– 2017 | Pediatrics | American Academy of Pediatrics \n(aap.org) \n22 Recommendations for Prevention and Control of Influenza in Children, 2022– 2023 | Pediatrics | American Academy of Pediatrics \n(aap.org) \n23 AAP. Technical Report for the 2022- 23 Recommendations for the Prevention and Control of Influenza in Children, 2022- 23 \n24 Greenhawt M et al. Ann Allergy Asthma Immunol 2018;120:49- 52 \n18 \n \n    \n     \n   \n \n  \n  \n   \n \n  \n   \n \n       \n      \n   \n \n   \n       \n  \n \n     \n   \n     \n     \n   \n       \n \n    \n \n    \n   \n   \n   \n    \n      \n  \n    \n \n     \n       \n    \n   \n  \n   \n     \n       \n   \n \n    \n         \n    \n     \n      airways should be available for immediate use.25 As a last piece of background, there are \nseveral past approaches to influenza vaccination of persons with e gg allergy that are not \ncurrently recommended , including the following: \nVaccine skin testing prior to vaccination:26 \n− Skin prick and/or intradermal testing with dilution of vaccine \n− If positive, vaccination deferred or administered via alternative dosing protocol \nGraded administration of vaccine:27 \n− Incrementally increasing volumes, often in 5 to 6 steps, sometimes with dilutions \nin early steps \n− 0.05 mL of 1:100 dilution→0.05 mL of 1:10 dilution→0.05 mL→0.1 mL→ 0.15 \nmL→0.2 mL, with observation periods after each dose (e.g., 15 minutes) \n− In the literature, these also are referred to “desensitization protocols ” \nSplit dosing of vaccine:28 \n− Most commonly 10% of dose volume→observation period→remaining 90% of \ndose volume, often with additional observation after final dose. \nThe policy question the WG addressed for this analysis regarded whether to no longer \nrecommend additional safety measures for persons with egg allergy of any severity, beyond \nwhat is recommended for any other persons presenting for influenza vaccination. In the \ndiscussion that follows, the proposed intervention was to no longer make the recommendation \nregarding vaccination setting for those with a history of severe allergic reaction to egg. With that \nbackground in mind, Dr. Grohskopf summarized the WG’s discussio n of the EtR F ramework . \nBeginning with the Public Health Importance domain regarding whether vaccination of egg-\nallergic persons is an issue of public health importance, influenza vaccination is important and \nrecommended for all persons 6 months and older. Come individuals are at increased risk of \nsevere illness due to influenza and some egg- allergic individuals might fall into this category. \nFor example, egg allergy is more common in younger age groups , sometimes resolves as \nchildren get older, and frequently co -exists with asthma. In one cross- sectional survey of 38,408 \nchildren,29 asthma prevalence was higher among children with egg allergy (46.5% ) than with the \nother 8 most common food allergies (33.2%). Younger children and people with asthma are \ngroups that are recognized as being at increased risk for severe influenza illness and are \npopulations for which barriers to vaccination might be more consequential. \nIn the WG discussion, a number of points were raised related primarily to potential increased \nrisks for some people with egg allergy in terms of how consequential the potential barriers may \nbe or if they even exist . On the one hand, current recommendations might be a real or \nperceived barrier to vaccination (e.g., by promoting hesitancy based on safety concerns, or \nproviding a reason to decline vaccination). This could be detrimental to egg allergy persons who \nare at increased risk of severe influenza. No data specifically examining or confirming that the \ncurrent recommendations as they stand are an actual barrier, but the existence of a real or \nperceived barrier is plausible. Conversely, some WG members raised the point that current \nrecommendations might be less of a barrier now than they were previously since the cell \n25 Kroger AT et al. https://www.cdc.gov/vaccines/hcp/acip -recs/general -recs/index.html \n26 Bierman CW et al. J Infect Dis 1977;136:S652- S655; and Miller JR et al. J Allergy Clin Immunol 1983;71:568- 173 \n27 Murphy KR et al. J Pediatr 1985;106(6):931- 933 \n28 James JM et al. J Pediatr 1998;133:624- 628 \n29 Samady W, Warren C, Wang J, et al. E gg allergy in US children. J Allergy Clin Immunol Pract. 2020;8(9):3066- 73 \n19 \n \n      \n      \n     \n          \n     \n     \n   \n \n      \n     \n  \n     \n     \n    \n    \n   \n    \n    \n  \n \n    \n   \n  \n    \n   \n    \n      \n    \n  \n       \n  \n     \n       \n \n    \n     \n    \n     \n   \n  \n     \n      \n     \n   \n    \n    \n  \n    \n     \n   \n   culture- based egg -free vaccine, Flucelvax Quadrivalent , is currently approved for individuals ≥6 \nmonths of age . Until relatively recently, it was only for 4 years and older. Now it goes to the \nyoungest age group that probably has the highest prevalence of egg allergy. However, it is \nimportant to consider that there is only 2 vaccine that is egg-free that is licensed for children <18 \nyears of age compared with 4 other vaccines that are egg -based. In polling on this question, \n95% of the WG responded either “yes” or “probably yes ” vaccination of egg- allergic individuals \nis an issue of public health importance, with only 6% of the total responding “probably no. ” \nFor the second domain of Benefits and Harms , a systematic literature view was conducted, and \na GRADE analysis was performed . There was somewhat of a disconnect because it seemed \nunlikely that data would be found directly addressing the question of whether having the \nadditional recommendation was consequential. Therefore, the review focused on the safety of \ninfluenza v accine in this population, addressing the question, “Does the available evidence \nconcerning the safety of influenza vaccine in persons with a history of egg allergy favor routine \nvaccination without additional safety measures , regardless of severity of previous allergic \nreaction to egg?” B ecause all egg allergy individuals are currently recommended to get \ninfluenza vaccine and they were are not looking at the question of whether to vaccinate or \nwhether to choose specific vaccines, this review focused solely on harms and did not include \nreview of efficacy or effectiveness data. \nIn terms of the PICO question, the population was persons of any age with a history of allergy to \neggs, or who had an allergic reaction to influenza vaccine believed to be secondary to egg \nallergy. The interventions included any influenza vaccine. The comparators of interest included \nplacebo, non- egg-based influenza vaccine, non- influenza control vaccines, no vaccine, or no \ncomparator. Within 4 hours of vaccination, the critical outcomes of death, anaphylaxis meeting \nBrighton Criteria Levels 1─3, anaphylaxis otherwise classified, and allergic symptoms requiring \nhospitalization. The 2 anaphylaxis outcomes were combined. Important outcomes included \nallergic reaction symptoms requiring outpatient or emergency department (ED) medical \nattention. This category included instances that were described as being treated with \nmedications, without explicit mention of whether there was outpatient or ED care . The second \nimportant outcome was allergic reaction including cardiovascular symptoms, respiratory symptoms, angioedema, or generalized urticaria. The basis for inclusion of this set of reactions \nwas that they fall short of anaphylaxis , but nonetheless might be considered worrisome. \nThe systematic review yielded a total of 47 reports describing 52 studies. There was only 1 \nrandomized study, which was a comparison of full -dose with the 10%/90% split dosing of \nvaccine. There was 1 VAERS report summary. The remainder were retrospective and \nprospective cohort studies and case series and 2 involved only recombinant vaccine, which is \negg-free. Of interest none of the studies included a relevant comparison group (e.g., an \nalternative intervention such as no intervention or a different vaccine, an egg- free vaccine, or no \nvaccine) . In general , these studies administered vaccine to a population of individuals with egg \nallergy and then followed them for reactions. Of the reports, 14 were abstracts only, with no \nrelated paper found and relat ively limited information. All of the papers , reports , and studies \nwere reviewed descriptively. However, 28 reports encompassing 31 studies were included in the \nGRADE analysis. The studies included in GRADE were of egg -based seasonal and monovalent \npandemi c vaccines only and included full- or split -dose administration. Those 2 administration \nmethods were combined in the data because after consultation with an allergist, it was \ndetermined that these 2 administration routes were similar from the point of view of risk of an \nadverse reaction. For the randomized study that compared full -versus split -dose, those 2 \nexperimental groups were combined, and this study was treated as a cohort study. Data with \nunknown or unclear vaccine type, unspecified administration protocols, that used a graded \n20 \n \n    \n     \n \n  \n  \n \n \n \n     \n    \n    \n   \n \n    \n     \n  \n   \n    \n  \n     \n      \n \n   \n      \n \n      \n    \n \n   \n  \n \n  \n  protocol of ≥3 steps to administer vaccine, or which had an unknown or unclear denominator \nwere excluded. Since there were no comparators, the data were summarized as frequencies. \nThis table summarize frequency of the events that occurred by vaccine type for persons with \negg allergies of all severities , with the results stratified these results by Seasonal IIVs *, \nMonovalent IIVs *, and live -attenuated influenza vaccine (LAIV ): \n*Includes several papers for which vaccine type not explicitly stated, but presumed based upon season, study location, and/or use of graded/split \ndosing. Seasonal IIV data include one paper describing a virosomal vaccine. \n†One study reported 6 instances of reactions including “wheezing, ecz ema exacerbation, or hives on chest”, but not specifying number with each \nsymptom. If assumed that all six included wheezing, frequency would be 11/1591=0.7% \nAll of the LAIV work was with seasonal vaccine. The seasonal IIV group included one virosomal \nvaccine, which was not available in the US. It was a study from Europe. GRADE and evidence \ncertainty for every vaccine and outcome were assessed separately. However, the results were \nall the same. Therefore, only one column was included for space considerations. Certainty \nlevels were very low across the board. With regard to the event frequencies, the included \npapers reported no occurrences of the three critical outcomes death, anaphylaxis , or \nhospitalization across vaccine type. For reactions requiring outpat ient or ED attention, \nfrequencies were 0.2% for seasonal IIV, 1.5% for monovalent IIV, and 0% for LAIV. \nInstances that involved treatment with symptomatic medications were included, which was the \nmajority of these. There were only 2 that referred explicit ly to transfer to an ED. For reactions \nincluding cardiovascular symptoms, respiratory symptoms, angioedema, or generalized \nurticaria, the frequencies were 0.3% for seasonal IIV, 0.6% for monovalent IIV, and 0.8% for \nLAIV. Again, certainty across the board was very low. These studies generally were all \nobservational studies , so they started with a certainty of low, so downgrading even for one \ncharacteristic would bring the certainty to very low. This work overall was downgraded mainly \nfor methodological quality and for imprecision. Because these data reflected data for people \nwith egg allergy of all severities and not just those who had a history of anaphylaxis to egg , it \nalso was downgraded for indirectness. \n21 \n \n    \n  \n \n \n \n     \n \n \n     \n   \n     \n    \n   \n     \n     \n   \n    \n     \n   \n \n \n   \n     \n    \n      \n    \n    \n      \n      \n       \n   \n    \n  \n    \n     \n  \n \n       This table sum marize frequency of the events that occurred by vaccine type for a subset of \npersons with anaphylaxis to eggs, with the results stratified these results by Seasonal IIVs *, \nMonovalent IIVs *, and live -attenuated influenza vaccine (LAIV ): \n*Includes several papers for which vaccine type not explicitly stated, but presumed to be IIV based upon season, study location, and/or use of \ngraded/split dosing. \nThis subset of individuals in these studies were found to have reported a history of anaphylaxis \nto egg. Since the policy question focuses on people who have a history of severe egg allergy, \nthis group was important to the WG and they were hoping to find as much as possible and the \ndata were stratified where possible. Overall , the numbers are lower. Some studies did not \ninclude people with severe egg allergy, did not mention whether people with severe egg allergy \nwere included, did not state the numbers of these people in the study , or did not report the \nfindings specifically for that subgroup. They might have reported reactions , but then did not go \non to say whether they occurred or how many of them occurred in people with anaphylaxis to egg. There were no events for any of the outcomes of interest for any vaccine type in this \nsubset. This is likely due, at least in part, to small sample sizes . Certainty for these outcomes \nwas rated as very low for each vaccine type as well, with downgrading primarily for \nmethodological quality and imprecision. \nTo summarizes , the certainty of evidence for the 3 critical and 2 important outcomes of interest \nwas very low for all 3 vaccine types. While studies without denominator data and those for \nwhich the vaccine was unclear were not included in the GRADE analysis, one particular report \nbears noting in this discussion. This was a report of Brighton Level 1 anaphylaxis that occurred \nin a person with “possible” egg allergy within 30 minutes of receiving monovalent vaccine. It was \nreported in a paper summarizing VAERS reports of AEs to monovalent pandemic vaccine \nduring the 2009- 2010 season.\n30 The information presented on the case in this paper is limited \nand it is unclear from the way it is described whether the recipient was documented to be egg \nallergic. It is referred to as a case of “possible” egg allergy. The reactions were included in the \ncounts in the GRADE evidence profiles because there was not a defined denominator, given \nthat these were VAERS data. While t he paper states that approximately 127 million doses of \ninfluenza vaccine were distributed that season; however , the number of doses that were actually \nadministered is unknown. Other reactions among egg- allergic persons reported in this paper \nincluded 2 described as respiratory hypersensitivity and 1 as a sensation of throat closure. \n30 Halsey NA, et al. Vaccine. 2013 Dec 9;31(51):6107- 12. doi: 10.1016/j.vaccine.2013.09.066. Epub 2013 Oct 8. PMID: 24120547. \n22 \n \n    \n       \n    \n  \n     \n     \n         \n    \n    \n   \n \n \n  \n   \n     \n      \n    \n     \n   \n    \n    \n     \n  \n     \n   \n \n    \n     \n    \n    \n      \n   \n      \n \n      \n     \n     \n    \n      \n     \n   \n  \n        \n   \n  \n          \n  \n  The papers related to egg- free vaccine discuss reactions following recombinant influenza \nvaccine were from Woo, et al 2015 and 2017. These are summaries of VAERS reports following \nadministration of recombinant influenza vaccine. They include reports of serious allergic \nreactions following RIV, some of which occurred among persons with egg allergy. RIV is egg- , \ngelatin-, antibiotic -, and preservative- free. Because RIV is an egg -free vaccine, these reactions \ncannot be assumed to be a manifestation of egg allergy. However, this literature brings up a \ncouple of points that probably are important. One that the authors note is that the occurrence of \nsuch reactions might reflect an underlying predisposition to atopy among egg- allergic \nindividuals. Also, it highl ights the importance of thinking about the unpredictability of severe \nallergic reactions and the importance of being prepared in all vaccination settings for all \nrecipients and with all vaccines. \nThere are a number of limitations to this review and the literature retrieved , which were \ndiscussed within the WG . These were observational data with no comparator groups meeting \ncriteria. Not only are the data observational, but also most of the cohort studies essentially were \ncase series because there was no comparator group. It is important to note that about 4 studies \nincluded a comparator group of non- egg-allergic people, but that was not the kind of comparator \ngroup that was going to provide the information needed. Some of the data were available only \nfrom abstracts, which had relatively limited details compared with the paper. Many of the \npapers, particularly the older papers , employed skin testing with egg proteins and/or vaccine \nprior to deciding to vaccinate or deciding how to vaccinate (e.g., full-versus split-dose ). \nTherefore, it is possible that there could have been some kind of selection bias caused by that \nprocedure. There is considerable variability in the level of detail in which outcomes are \ndescribed, particularly in abstracts for which descriptions are scant. Even among the full papers \nthere is variability in the level of detail. \nIt is probably reasonable to assume that serious reactions , such as death or anaphylaxis , are \nmore likely to be reported than less serious ones. E ven among less serious ones, there was \nsome variability. Most studies had a follow -up period for delayed reactions to be reported by \nparents or caregivers, perhaps 24 to 72 hours after discharge from the vaccination setting, but it \nis easy to see how some of these reactions might not be described as well and instances of \noutpatient care or hospitalizations might be missed. The observation time post -vaccination \nvaried and often was not reported for the delayed reactions. While the WG was trying to be \nconserv ative with the 4- hour window after vaccination, observation times ranged between 30 \nminutes and 2 hours across the board . Even authors who reported delayed vaccinations often \ndid not report the elapsed time post -vaccination, which made the data difficult t o use. Ovalbumin \ncontent was not reported or was unknown in most instances. Some authors did report it, relying \non either the package insert or having the vaccine assayed themselves. In most instances \nwhere noted, it was under 1 microgram per dose and subs tantially less in some cases . In \nparticular, the monovalent vaccine Arepanrix ™ was used in some of the studies . Arepanrix ™ has \nas unusually low ovalbumin content as did the virosomal vaccine, which was in one of the \nstudies. It is difficult to know how this compares with current vaccines, since the package insert s \nfor current vaccines express this information as an upper limit. A number of papers have show n \nthat the quantity of ovalbumin can vary from lot -to-lot. Finally , and perhaps most important, data \nspecifically for people with anaphylaxis to egg were very limited. Not all studies specified \nincluded them and some did not include them. Where they were included, the data were not \nalways reported s pecifically for that population. \n23 \n \n      \n     \n   \n  \n      \n    \n     \n   \n     \n   \n \n \n  \n       \n     \n     \n \n \n  \n  \n   \n  \n     \n     \n    \n    \n      \n \n   \n     \n  \n  \n        \n    \n     \n \n  \n \n      \n    \n     \n \n     \n   \n  \n    \n   \n     \n     \n      \n    In terms of e gg allergy and a naphylaxis reports after IIVs in VAERS between 2017─2022, \ncolleagues in the Immunization Services Office ( ISO) did a brief review of VAERS reports for \negg allergy and anaphylaxis for the 2017─ 2022 period. In the review of VAERS reports , there \nwere 178 anaphylaxis reports after IIVs, 18 of which were reported to have an egg allergy. \nClinical review of these reports revealed 7 reports of anaphylaxis and egg allergy (4 among \nchildren, 3 among adults ), all of which occurred in the 2017─2018 season. T here were 4 \nBrighton Level 1, 1 Brighton Level 3, and 2 that did not meet Brighton. Associated i nfluenza \nincluded Fluarix Quad in 2 instances, Fluzone Quadrivalent in 2 instances, Fluvirin Trivalent in 1 \ninstance, Flucelvax Quadrivalent in 1 instance, and Flublok Quadrivalent in 1 instance. It is \ndifficult to assess whether the reaction was due to egg protein in these instances due to limited \nlaboratory data. \nWith regard to the question of benefits and harms, because this review focused solely on safet y \nliterature, only 1 of the benefits and harms questions was addressed. For the question of how \nsubstantial the undesirable anticipated effects are, 83% of respondents (N=18) selected either \n“small” at 44%, or “minimal” at 39%. There was 1 vote (6%) for “moderate” and 11% selected \n“varies. ” \nMoving to the Values domain and the question regarding whether the target population feel s \nthat the desirable effects are large relative to the undesirable effects, no direct evidence was \nfound to support any conclusions. It was raised that a change in the recommendations might be \nreassuring to some who have wanted to be vaccinated but were hesitant or perceived it to be \nunsafe. It also was raised that it might be a source of concern for some people, with 1 WG \nmember expressing that the change might be viewed unfavorably if it was perceived as a \ntradeoff between safety versus increasing coverage and reducing missed opportunities to \nvaccinate. For this question, there was not a majority opinion for any single answer, but half of \nrespondents responded indicated “ Don't Know” probably reflecting lack of information to inform \nthis particular question. There was considerable dispersion among the other options, although none selected “No.” Regarding whether there is important uncertainty about or variability in how \nmuch people value the main outcomes, no direct evidence was found to support conclusions \nhere. Presumably, greater value might be attached to the more serious outcomes, such as \ndeath, anaphylaxis, and hospitalization, which were the critical outcomes. But again, no data \nwere found to support this. For th e values question whether there is important uncertainty about, \nor variability in, how much people value the main outcomes , there was a clearer majority of \nresponses, with 67% indicating that they felt that there was “probably not important uncertainty \nor variability ” in how people value the main outcomes. However, 28% selected that there is \n“probably important uncertainty or variability. ” \nRegarding the Acceptability domain, no direct evidence was found from stakeholders. However, \nthere was some information that speaks indirectly to the possibility of acceptability. Some \ninformation speaking for acceptability includes the fact that several US professional societies \n(AAP, AAAAI, ACAAI) already recommend that no special measures, screening, observation \nperiods, selection of specific vaccines, or specific vaccination settings are needed for those with \negg allergy. A potential factor against acceptability is that as of 2022 ─2023, packaged inserts \nfor egg- based vaccines continue to carry a contraindication for severe hypersensitivity reactions \nto any vaccine components which for egg includes egg- based vaccines. This could cause \nconfusion among providers and consumers. However, this is a contraindication that has been in \nplace for quite some time and ACIP has recommended influenza vaccination for a number of \nseasons with any appropriate vaccine, including egg- based vaccines for people with egg allergy \nregardless of severity to reaction to egg. Therefore, there is probably not an a priori reason to \nassume that a change in recommendations would affect acceptability substantially . In further \n24 \n \n    \n  \n     \n     \n  \n    \n     \n   \n    \n  \n     \n \n    \n  \n        \n    \n   \n      \n   \n     \n    \n      \n   \n  \n \n       \n   \n   \n \n \n \n   \n    \n  \n   \n \n  \n \n  \n   discussion with the WG , considerations regarding acceptability included the idea that alignment \nof recommendations among public health organizations and professional societies facilitates \nconsistent messaging to providers and patients. However, some express ed the concern that \nsome settings might not be prepared to manage severe reactions, even though the guidelines state that preparation should be in place, and further that acceptability could be severely \nnegatively impacted if the anaphylaxis occurs in a setting unprepared to manage it —particular ly \nif there is a bad out come. The same WG member raised the importance of stressing that every \nsetting must be prepared to manage anaphylaxis or should not be administering any vaccine to \nany recipient. Finally, there was concern for potential liability issues. With regard to whether a \nchange in recommendations would be acceptable, 44% of 18 respondents indicated “Yes” while \n56% indicated “Probably Yes,” with no responses in the negative. \nFor the R esource Use domain, following consultation with the NCIRD Health Economist, no \neconomic  analysis was conducted for this review. One r eason was that the target population is \nsmall. T here also is lack of data for some factors that would be important in constructing the \nneeded assumptions for an economic model. For example, there is not a reliable estimate on \nthe proportion of those with egg allergy who have had severe reactions to egg. The proportion of individuals with egg allergy by age, particularly in older age groups , is uncertain. Importantly, \nthere is little information on the proportion of persons with egg allergy who are receiving egg -\nbased versus egg -free vaccines. Finally, the primary emphasis of this review was on safety \nrather than cost. While the intervention discussed here is not really one that has to do with the \nvaccines per se and the WG did not discuss whether to recommend some vaccines over others, \nthe point was raised that a change in recommendations with regard to setting could lead to \ninfluenza vaccination of egg- allergic persons being achieved in a more widespread manner in \nmore settings, and that could lead to a change in the balance of use of egg- free versus egg-\nbased vaccines in this population. With that in mind, the WG examined cost data. While a verage \nwholesale cost data were not available , some information was obtained from CMS payment \nallowances and the VFC. This table reflects these data, rounded to the nearest dollar :\n31 \nOverall , CMS payment allowances and VFC costs are higher for the egg- free vaccines that are \napproved for c hildren. In particular for both the multi -dose and preservative the single- dose \nformulations of Flucelvax Quadrivalent, the egg- free subculture based vaccine costs are about 9 \nto 11 dollars higher than the average corresponding presentation for the egg -based inactivated \nvaccines. \n31 https://www.cms.gov/Medicare/Medicare- Fee-for-Service -Part-B-drugs/McrPartBDrugAvgSalesPrice/VaccinesPricing ; and CDC \nVaccine Price List (Private sector cost per dose) \n25 \n \n     \n    \n   \n  \n     \n   \n     \n  \n \n   \n  \n   \n  \n  \n    \n   \n   \n   \n  \n     \n \n \n     \n \n    \n   \n    \n      \n  \n    \n  \n  \n    \n   \n    \n \n  \n     \n     \n   \n    \n  \n      \n    \n     \n    \n    \n  \n \n    \n     \n  The WG considerations around the issue of resource use included that removing existing \nrestrictions possibly could result in a more efficient allocation of resources if the data suggests \nno or minimal increase in AEs. Conv ersely , a change in recommendations and lower cost of \negg-based vaccines might lead to their increased use, which might be associated with \nincreased cost if there is increase in reactions that require medical attention. With regard to \nwhether the intervent ion is a reasonable and efficient allocation of resources , of 18 respondents , \n1 was excluded who selected 2 options. Of the 17 remaining, 76% responded “Yes” and 24% \nresponded “Probably Yes.” \nRegarding the Equity domain, no direct evidence was identified that would affect conclusions in \nthis particular population of egg -allergic individuals. However, some indirect evidence \nconcerning the risk of some populations to severe influenza illness and the prevalence of egg \nallergy are raised here as potential indirect lines of evidence. For example, some racial and \nethnic groups are at increased risk of severe influenza illness, highlighting the importance of \ninfluenza vaccination. One paper recently reported that influenza -associated hospitalization and \nICU admiss ion rates were higher among B lack, Hispanic, and AI /AN children under 4 years of \nage compared with white children.32 Additionally, some studies indicate that some groups are \nmore likely to have food allergies. For example, Black children were disproportionately \nrepresented among children with egg allergy in one series .33 If current recommendations are a \nreal or perceived barrier to vaccination, the intervention potentially could improve equity with \nregard to risk of severe influenza illness in this population. \nIssues related to trust in the healthcare system were raised by a couple of WG members as \npotentially negative impacts. Again, this is not about recommending egg -based versus non -egg-\nbased vaccines . Instead, this point brings together the issues of cost, equity, and trust. The \nproposed recommendation focuses on language related to vaccination setting. People with egg-\nallergy are currently recommended to receive any vaccine that is otherwise appropriate, even if \nit is egg-based. However, a change in recommendations might mean that the vaccination \noccurs more widely in more settings than previously . Perhaps with increased use of egg -based \ninfluenza vaccines rather than egg- free vaccines in some settings could be influenced by their \nrelative cost. The fact that egg -based vaccines are less expensive might reinforce the bel ief that \nvaccination providers do not care to use the necessary resources to provide a potentially safer \nvaccine. With regard to impact on health equity, the WG responses were dispersed. This \npossibly reflect s uncertainty given the lack of specific data. H owever, 50% of the 18 \nrespondents expressed that equity would be “P robably Increased. ” \nFor the last domain of F easibility , a number of considerations were raised. Considerations \nfavoring feasibility are that the proposed change is a simplification of the previous \nrecommendation. It involves removal of an extra recommendation for 1 subgroup, and it makes \nthe recommendations for vaccination of egg- allergy persons uniform regardless of severity and \nbasically similar to the recommendations for vaccination of any person against influenza. It also \ndoes not specify particular vaccines and does not change recommendations for emergency equipment and resources in vaccination settings. As noted, the General Best Practices already \nindicate that equipment and medicines to manage potential severe allergic reactions should be \navailable in all vaccination settings.\n34 A consideration against feasibility is that there might be \nsome vaccination settings that are not already prepared to manage severe aller gic reactions, \nand such settings would need to address these needs. Again, all settings already are \nrecommended to be prepared for severe allergic reactions when administering any vaccine to \n32 O’Halloran et al JAMA Netw Open. 2021 Aug 2;4(8):e2121880 \n33 Samady W et al. J Allergy Clin Immunol Pract. 2020 Oct;8(9):3066- 3073.e6. doi: 10.1016/j.jaip.2020.04.058 \n34 Kroger AT et al.  https://www.cdc.gov/vaccines/hcp/acip- recs/general -recs/index.html \n26 \n \n       \n    \n \n    \n   \n    \n  \n     \n    \n \n \n \n   \n    \n  \n  \n   \n      \n  \n \n    \n  \n  \n     \n    \n  \n \n     \n      \n    \n   \n    \n   \n     \n       \n      \n    \n      \n  \n   \n   \n     \n  \n  \n \n      \n     \n  \n     any recipient. With regard to whether the intervention is feasibl e, 89% of the 18 respondents \nanswered “Yes” and 11% answered “Probably Yes.” \nIn terms of the b alance of consequences and sufficiency of information, 61% of the 18 \nrespondents i ndicated that the “D esirable consequences clearly outweigh undesirable \nconsequences in most settings ” and 39% responded that the “D esirable consequences probably \noutweigh undesirable consequences in most settings. ” With regard to whether there is sufficient \ninformation to move forward with a vaccination, 100% of the 18 respondents answered “Yes” \nand 0% responded “No.” \nInfluenza Vaccine Safety Update and Proposed Recommendations for the 2023- 2024 \nInfluenza Season \nLisa Grohskopf MD, MPH (CDC/NCIRD) presen ted a brief influenza vaccine safety update and \nthe proposed recommendations for the votes. Approximately 173 million doses of influenza \nvaccines were distributed in the US for the 2022- 2023 season.35 In VAERS, which is co -\nmanaged by CDC and FDA, no new safety concerns were identified for influenza vaccines. In \nthe VSD, which is a collaboration between CDC and 9 integrated healthcare organizations \nwithin the VSD, approximately 5.5 million doses of influenza vaccine were distributed for the \nseason. N o new safety concerns were identified in influenza vaccine monitoring.36 However, a \nstatistical signal for ischemic stroke after Pfizer -BioNTech Bivalent mRNA COVID -19 vaccine in \npersons ≥65 years of age that was detected in a VSD analysis for COVID -19 vaccine safety \nmonitoring .37 Post-signal analys es in VSD found an elevated rate ratio for ischemic stroke after \nsimultaneous vaccination with Pfizer -BioNTech Bivalent mRNA COVID -19 vaccine and high-\ndose or adjuvanted influenza vaccine, which has attenuated over time. Separate analyses did \nnot detect elevated rate ratios for ischemic stroke after influenza vaccine administered without \nbivalent mRNA COVID- 19 vaccine. \nTo provide an overview of the proposed recommendations for 2023- 2024, vaccination of all \npersons ≥6 months of age who do not have contraindications continues to be recommended. \nAdditionally, no changes were proposed for the recommendations regarding timing of \nvaccination compared to the past season. Proposed changes include the updated US influenza \nvacci ne composition for 2023- 2024 and proposed changes to the recommendations for \nvaccination of persons with egg allergy. As noted, the timing of vaccination recommendations \nare unchanged from last season. Because this information is important for programs in terms of \nplanning their influenza vaccine campaigns for the upcoming season, Dr. Grohskopf reviewed \nthem briefly. The overarching recommendation is that for most persons who need only 1 dose of \ninfluenza vaccine for the season, vaccination ideally should be offered during September or \nOctober. The reason that is the case and not earlier is because of concerns about waning of \nimmunity during the season. However, vaccination among vaccinated persons should continue \nafter October a nd throughout the season as long as influenza viruses are circulating and \nunexpired vaccine is available. Vaccination during July and August are not recommended for \nmost groups due to concerns for waning immunity. Considerations for July and August \nvaccina tion are noted for adults, children, and pregnant persons. \n35 Weekly Flu Vaccination Dashboard | FluVaxView | Seasonal Influenza (Flu) | CDC \n36 Outcomes monitored in VSD: acute disseminated encephalomyelitis, anaphylaxis, Bell’s Palsy, encephalit is, Guillain -Barré \nsyndrome, seizures, transverse myelitis \n37 Shimabukuro T, ACIP presentation on April 19, 2023 mRNA COVID -19 bivalent booster vaccine safety update (cdc.gov) \n27 \n \n      \n   \n     \n          \n  \n    \n       \n   \n      \n        \n     \n  \n    \n    \n      \n     \n   \n  \n   \n \n    \n        \n    \n    \n   \n    \n    \n   \n   \n   \n \n  \n  \n \n  \n  \n \n   \n \n   \n \n  \n \n \n  For most adults, particularly adults ≥65 years of age, and for pregnant persons in the first or \nsecond trimester, vaccination during July and August should be avoided unless there is concern that vaccination later in the season might not be possible (e.g., concern that an opportunity to \nvaccinate at all might be missed) . This is because , particularly for adults ≥65 years of age, there \nis a concern about waning immunity over the course of the season that has been documented in \nall age groups but appears to be the most pronounced among older adults. There are 2 \nrecommendations for children. Children who require 2 doses who are ≥6 months ─8 years of \nage who have an unclear or unknown influenza vaccination history or who have not received a \nlifetime total of 2 doses should receive their first dose as soon as possible, including during July \nand August if vaccine is available, to allow for the second dose that is to be administered 4 \nweeks later to be give n ideally by the end of October. For c hildren who require only 1 dose, \nvaccination during July and August can be considered. This is because waning has been \ndocumented in all age groups , although t here are less data currently for children. Moreover, \nschool -aged children commonly present to HCP in the late summer months for preschool \nphysicals, which presents a vaccination opportunity that should be considered if that child is not \nexpected to be seen again prior to the season. For pregnant people in the third trimester, \nvaccination during July and August can be considered because vaccination might reduce risk \nfor influenza illness in their infants during the first months after birth when they are too young to \nreceive influenza vaccine. This has been documented in a number of studies. \nIn terms of the US influenza vaccine composition for 2023 -2024, there is only 1 proposed \nchange that comes from the FDA. FDA’s VRBPAC met in early March as usual to select the \nrecommended composition for the next season.\n38 All vaccines available expected to be \navailable in the US for the next season will be quadrivalent.  The 2023 -2024 composition \nincludes updated influenza A(H1N1)pdm09 components for both egg- based and non -egg-based \nvaccines. Interestingly, this has caused some confusion and questions because the \nA(H1N1)pdm09 components last year also were a n influenza A/Victoria and an influenza \nA/Wisconsin , but they were different with slightly different numbers in their taxonomy. The \ncomponents for the H3N2 and both B viruses are the same as last season. All US -licensed \ninfluenza vaccines will include hemagglutinin derived from the following: \nAn influenza A/Victoria/4897/2022 (H1N1)pdm09 -like virus (egg -based vaccines) \nAn influenza A/Wisconsin/67/2022 (H1N1)pdm09 -like virus (cell and recombinant vaccines) \nAn influenza A/Darwin/9/2021 (H3N2) -like virus (egg -based vaccines) \nAn influenza A/Darwin/6/2021 (H3N2) -like virus (cell and recombinant vaccines) \nAn influenza B/Austria/1359417/2021- like virus (B/Victoria lineage) \nAn influenza B/Phuket/3073/2013- like virus (B/Yamagata lineage) \n38 https://www.fda.gov/advisory- committees/advisory -committee- calendar/vaccines -and-r elated- biological -products -advisory -\ncommittee- march -7-2023- meeting -announcement \n28 \n \n      \n     \n \n           \n  \n   \n \n   \n    \n \n \n   \n \n \n \n \n \n \n \n \n      \n   \n  \n \n  \n  \n \n   \n  \n  \n  \n \n  \n \n \n \n \n \n The proposed recommendation language for vaccination of persons with egg allergy was \ndrafted for the ACIP’s consideration and editing as appropriate: \nAll persons aged ≥6 months with egg allergy should receive influenza vaccine unless a\ncontraindication exists. Any influenza vaccine that is otherwise appropriate for the recipient’ s\nage and heal\nth status can be used (egg based or non- egg based) .\nE\ngg allergy in and of itself necessitates no additional safety measures for influenz a\nv\naccination beyond those recommended for any recipient of any vaccine, regardless  of\ns\neverity of previous reaction to egg .\nS\nevere and life- threatening reactions to vaccines can rarely occur with any vaccine and i n\nany\n vaccine recipient, regardless of allergy history. Providers are reminded that all vacci nes\ns\nhould be administered in settings in which personnel and equipment needed for rapi d\nr\necognition and treatment of acute hypersensitivity reactions are available. All vaccinati on\npr\noviders should be familiar with their office emergency plan and be certified i n\nc\nardiopulmonary resuscitati on.\nV\nFC Resolution \nJeanne Santoli, MD, MPH (CDC/NCIRD) indicated that the purpose of this resolution was to: 1) \nupdate the product table in the IIV component of the resolution; 2) revise the eligible groups \nsection in the LAIV component of the resolution; and 3) add/update the links in the contraindications and precautions section of both components of the resolution. The eligible \ngroups are all children 6 months ─18 years of age. There are no changes to the vaccine \nschedule and recommended dosage intervals are as follows: \n6 months through 8 years: 1 or 2 doses, as noted in the current ACIP recommendati\nons\n9 t\nhrough 18 years: 1 dos e\nM\ninimum age: 6 mont hs\nM\ninimum interval between dose 1 and dose 2 (where applicable): 4 week s\nTh\nis table lists the currently approved IIVs in the VFC program, including the age indication for \neach vaccine, with the only change being removal of a product that is no longer available in the \nUS: \n29 \n \n   \n   \n \n   \n  \n   \n \n \n   \n    \n    \n   \n \n \n  \n   \n  \n \n \n    \n \n    \n \n   \n  \n  \n   \n \n    \n  \n  \n  \n \n \n \n \n \n  \n   \n   \n \n  Recommended Dosage Refer to product package inserts available at: \nhttps://www.fda.gov/vaccines -blood- biologics/vaccines/vaccines -licensed- use-united- states \nFor the contr aindications and precautions, some guidance was removed about the use of \nvaccine in egg- allergic individuals that was thought to be potentially confusing. Instead, a link \nwas added to the details about the contraindications and precautions. \nContraindications: \n1. For egg -based IIV: History of severe allergic reaction (e.g., anaphylaxis) to any component \nof the vaccine (other than egg) or after previous dose of any influenza vaccine. \n2. For cell culture- based IIV: History of severe allergic reaction (e.g., anaphyl axis) to cell \nculture- based IIV or any component of the vaccine. \nPrecautions: \n1. Moderate or severe acute illness with or without fever \n2. GBS within 6 weeks following a previous dose of influenza vaccine \n3. For cell culture- based IIV only: History of severe allergic reaction to any other influenza \nvaccine. \nDetails of contraindications and precautions can be found at Prevention and Control of \nSeasonal Influenza with Vaccines: Recommendations of the Advisory Committee on Immunization Practices — United States, 2022– 23 Influenza Season | MMWR (cdc.gov). \nFor the LAIV section, the eligible groups were reworded to remove reference to potential precautions for vaccination and instead indicate that the eligible groups are non- pregnant \nchildren and adolescents aged 2 through 18 years. The recommended vaccination schedule \nand dosing i ntervals were unchanged: \n2 years through 8 years: 1 or 2 doses, as noted in the current ACIP recommendations \n9 through 18 years: 1 dose \nMinimum Age: 2 years \nMinimum interval between dose 1 and dose 2 (where applicable): 4 weeks \nThe dosage and contraindications and precautions section was unchanged except for an update to the link in this section to match the latest published statement. The statement regarding \nupdates based on published documents did not change from the following: \n[If an ACIP recommendation regarding influenza vaccination is published within 6 months \nfollowing this resolution, the relevant language above (except in the eligible groups sections) \nwill be replaced with the language in the recommendation and incorporated by reference to the \nURL]. \n30 \n \n  \n \n     \n  \n \n \n          \n  \n  \n \n \n   \n \n \n    \n  \n \n          \n   \n         \n        \n \n \n \n  \n \n    \n \n \n \n    \n \n  \n \n \n    \n \n \n    \n  \n \n          \n   \n         \n        \n \n  Vote #1: Influenza Vaccination Recommendation \nDr. Lee (ACIP Chair) displayed and read the proposed vote language following the public \ncomment period. The vote was combined with the Influenza Vaccine session for ease of \nreading: \nAll persons ages ≥6 months with egg allergy should receive influenza vaccine. Any \ninfluenza vaccine (egg based or non- egg based) that is otherwise appropriate for the \nrecipient’s age and health status can be used. \nMotion/Vote #1: Influenza Vaccination Recommendation \nDr. Poeling made a motion to approve the recommendation as stated, which Ms. Bahta \nseconded. No COIs were declared. The motion carried with 14 affirmative votes, 0 negative \nvotes, and 0 abstentions. The disposition of the vote was as follows: \n14 Favored: Bahta, Bell, Brooks, Chen, Cineas, Daley, Kotton, Lee, Loehr, Long, McNally, \nPoehling, Sanchez, Talbot \n0 Opposed: N/A \n0 Abstained: N/A \nVote #2: Influenza Vaccination MMWR Recommendations and Reports \nDr. Lee (ACIP Chair) displayed and read the proposed vote language following the public \ncomment period. The vote was combined with the Influenza Vaccine session for ease of reading: \nAffirm the updated MMWR Recommendation and Reports, “Prevention and Control of \nSeasonal Influenza with Vaccines: Recommendations of the Advisory Committee on \nImmunization Practices —United States, 2023 -24 Season.” \nMotion/Vote #2: Influenza Vaccination MMWR Recommendations and Reports \nDr. Poeling made a motion to approve the recommendation as stated, whic h Dr. Daley \nseconded. No COIs were declared. The motion carried with 14 affirmative votes, 0 negative \nvotes, and 0 abstentions. The disposition of the vote was as follows: \n14 Favored: Bahta, Bell, Brooks, Chen, Cineas, Daley, Kotton, Lee, Loehr, Long, McNally, \nPoehling, Sanchez, Talbot \n0 Opposed: N/A \n0 Abstained: N/A \n31 \n \n  \n  \n \n    \n \n \n \n   \n \n \n   \n \n \n    \n  \n \n          \n   \n         \n        \n \n \n \n \n \n \n \n    \n    \n \n \n  \n \n   \n     \n  \n \n \n \n  \n \n \n  \n \n    \n    \n     \n    \n  Vote #3 : Influenza Vaccine VFC Resolution \nDr. Lee (ACIP Chair) displayed and read the proposed vote language following the public \ncomment period. The vote was combined with the Influenza Vaccine session for ease of \nreading: \nApprove the Vaccines for Children (VFC) resolution for influenza vaccines. \nMotion/Vote #3 : Influenza Vaccine VFC Resolution \nDr. Poeling made a motion to approve the recommendation as stated, which Dr. Daley \nseconded. No COIs were declared. The motion carried with 14 affirmative votes, 0 negative \nvotes, and 0 abstentions. The disposition of the vote was as follows: \n14 Favored: Bahta, Bell, Brooks, Chen, Cineas, Daley, Kotton, Lee, Loehr, Long, McNally, \nPoehling, Sanchez, Talbot \n0 Opposed: N/A \n0 Abstained: N/A \nPUBLIC COMMENTS \nOverview \nThe floor was opened for public comment on June 21, 2023 at 4:15 PM ET. Given that many \nmore individuals registered to make oral public comments than could be accommodated during \nthis meeting, selection was made randomly via a lottery. Dr. Lee provided a gentle reminder that \nthe ACIP appreciates diverse viewpoints that are respectful in nature and issue- focused rather \nthan comments directed at individuals. The comments made during the meeting are included in this document. Members of the public also were invited to submit written public comments to \nACIP through the Federal eRulemaking Portal under Docket Number ID CDC -2023- 0035. Visit \nhttp://www.regulations.gov for access to the docket or to submit comments or read background \ndocuments and comments received. The public comment session occurred prior to the votes, \nbut the votes were connected back with their respective sessions for ease of reading. \nPublic Comment \nLindsay Clarke, JD\nSenior Vice President \nHealth Education and Advocacy\nAlliance for Aging Research \nGood afternoon and thank you to the committee for this opportunity to comment. My name is \nLindsay Clarke. I am the Senior Vice President of Health Education and Advocacy at the \nAlliance for Aging Research. One of the educational campaigns that I lead at the Alliance is the “Our Best Shot ” campaign. Over the years, this campaign has produced dozens of educational \nresources focused on raising awareness about the importance of vaccines in older adults, how \n32 \n \n     \n    \n    \n    \n \n    \n    \n      \n  \n    \n   \n     \n    \n     \n  \n  \n   \n    \n  \n     \n   \n    \n   \n \n  \n   \n  \n \n \n \n  \n \n \n  \n      \n    \n   \n \n  \n   \n    \n  \n    \n   \n    \n  \n  \n    \n  \n  \n they work, which ones are recommended by this committee, how the Medicare program covers \nvaccines , and more. The resources have included a focus on influenza, pneumonia, shingles , \nand COVID. In this past year, we’ve produced educational films on RSV in older adults, \nemphasizing to viewers that RSV is not just a pediatric disease. While we know that older adults \nare especially vulnerable to serious complications from RSV, we also know that adults ages 60 \nto 64 living with asthma, congestive heart failure, COPD are all at high risk for RSV related \nhospitalizations and deaths. Additionally, studies from the CDC and others presented at the \nReSViNET conference in January demonstrate that a higher proportion of adults ages 60 to 64 \nwho were hospitalized and/ or experienced severe outcomes due to RSV were Black, Hispanic, \nor American Indian/ Alaskan Natives. These racial and ethnic defenses are critical to consider \nwhen determining age recommendations for the new RSV vaccines. Earlier and higher rates of \nasthma, congestive heart failure, or COPD in communities of color due to structural racism led \nto earlier RSV onset and higher risk of hospitalization, severe outcomes, including deaths , and \nmust be considered as part of the age recommendations. Once the recommendations are \ndetermined, we urge publication in the MMWR without delay. While respiratory surges are no longer limited to the traditional cold and flu season, we know that the surges of influenza, \nCOVID, pneumoni a, RSV, and other respiratory illnesses continue to flood and overwhelm our \nhealthcare system in the fall and winter months. Being able to start administering these \nvaccines for the fall season will undoubtedly save lives. Lastly, we urge the federal gover nment \nto make sure that the safety of co -administering multiple vaccines like RSV, influenza, COVID , \nand pneumonia is clearly communicated. We know from our education and outreach that \nmisinformation about the safety of receiving multiple vaccines at once persists and clear \ncommunication from the FDA, CDC , and other agencies is critical in the distribution of reliable \nand trustworthy information on vaccination and specifically on co- administration. We are excited \nabout the new RSV vaccines, and while general awareness and prevention will remain a priority \nfor the Alliance, we look forward to being able to encourage older adults and all adults at high \nrisk to receive an RSV vaccine to protect themselves and their loved ones. Thank you again for this opportunity to comment. \nErica DeWald \nChief Communication Officer \nVaccinate Your Family \nThank you and good afternoon. I am the Chief Communication Officer at Vaccinate Your Family, \nan organization you will hear about from my colleague, Serese Marotta , in just one moment. \nThank you for the opportunity to comment. I wanted to thank the ACIP voting members and \nliaisons for all of their hard work in recent years. While many in the general public first became \naware of ACIP during the pandemic, our organization has held the ACIP in the highest regard \nfor decades. Our policies specifically stipulate that Vaccinate Your Family follow the \nrecommendations of this committee. This week ’s meeting showcases the depth and the breadth \nof the work you do. ACIP serves a critical role in ensuring the safety and efficacy of our vaccine \nschedule in the US. As independent experts, your review of the available data presents an unbiased view of how best to protect people in this country. Science and the data it creates \nshould always lead the way on vaccination recommendations. As you consider votes on \npneumococcal and RSV vaccines as well as the reformulation of the COVID -19 vaccines, \nVaccinate Your Family urges you to continue to consider the available data. Too often in recent \nyears, politics have attempted to replace science. The ACIP has remained firm in their \ncommitment to follow the data. We hope others will in turn continue to follow the ACIP and \nrespect their independent review of the safety and effectiveness of new and existing vaccines. \nThank you again for the opportunity to comment. \n33 \n \n  \n  \n \n \n  \n    \n   \n    \n     \n    \n    \n  \n  \n   \n     \n  \n    \n   \n   \n \n   \n       \n   \n \n     \n      \n   \n      \n    \n    \n     \n     \n \n \n \n  \n \n \n    \n  \n   \n \n   \n     \n  \n   \n    \n      \n     \n    \n    Serese Marotta \nDirector of Advocacy and Education\nVaccinate Your Family \nGood afternoon. Hello, I ’m Serese Marotta, Director of Advocacy and Education at Vaccinate \nYour Family. On behalf of Vaccinate Your Family, thank you for the opportunity to comment \ntoday. Established 30 years ago, Vaccinate Your Family wor ks to protect people of all ages from \nvaccine- preventable diseases through advocacy, education, and policy. As evidenced by the \nCOVID -19 pandemic, there is still much work to do to improve health equity and this is a priority \nfor our organization. While we recognize that ACIP is discussing several important topics this week, my comments will focus primarily on respiratory syncytial virus, also known as RSV. Our \norganization is pleased that the committee will be considering recommendations for RSV \nvaccines for older adults, and we sincerely appreciate the robust discussions this morning. RSV \ninfections in older adults result in 60,000 to 160,000 hospitalizations and 6,000 to 10,000 deaths \nevery year in the United States. Recent studies found that the economic burden of RSV \ninfections on healthcare systems was substantial, with RSV hospitalizations resulting in a national direct cost burden of $1.5 to $ 4.0 billion dollars for adults greater than 60 years old. \nGiven the public health and economic burdens of RSV on older adults in the US, it is imperative \nthat we have preventive measures like vaccines available as early as possible to help protect \nolder adults from this disease. RSV can also be serious for infants and young children. Every \nyear in the US, 58,000 to 80,000 children younger than 5 years old are hospitalized with RSV, \nand an estimated 100 to 300 children younger than 5 lose their lives to it. RSV not only causes \na significant public health burden for young children, but also it creates a serious economic \nburden for families. According to a recent national survey, more than 2/3 of parents said that RSV caused a financial burden or crisis to their family. RSV has disproportionate impacts on \nBlack and Hispanic /Latino infants as well as those on Medicaid, which is why it is so important \nthat we have equitable access to preventive measures, including tools like monoclonal \nantibodies and maternal vaccinations. The past ‘22─’23 seasons saw a resurgence of RSV, \nalong with other respiratory diseases like flu and COVID, resulting in a triple- demic that puts \nserious strains on our healthcare systems. We urge ACIP to follow the science and, if possible, \nprovide timely recommendations prior to the start of the next RSV season this Fall. This means \nthe inclusion of passive immunizations in the VFC program and the timely publication of the \nMMWR . \nMartha Nolan, JD \nSenior Policy Advisor\nHealthyWomen \nGood afternoon. My name is Martha Nolan. I am the Senior Policy Advisor for HealthyWomen, \nan advocacy organization committed to educating women so they can make informed health \nchoices, advocate for themselves, and prioritize their health and wellness. For thousands of \nwomen across the country, we are a trusted source for credible, up -to-date information r elevant \nto their mental and physical well -being and we believe a critical aspect of business preventive \ncare. We understand the vital role that vaccines play in protecting against severe disease and are a strong proponent of ensuring that women and their families have the information they need to make informed decisions about their vaccine options. Last year ’s unexpected influx of \nRSV cases, on top of the already active flu, COVID , and pneumonia season, presented a stark \nreminder of why continued innovation in vaccines is so necessary. At the time, many adults \nwere learning about the risk of RSV for older Americans for the first time, and there were no \nvaccines available to protect themselves. We know that on average, as many as 160,000 adults 65 and older are hospitalized for RSV, and up to 10,000 older adults die each year from the \n34 \n \n     \n   \n    \n    \n     \n  \n  \n     \n  \n     \n     \n  \n  \n    \n    \n  \n   \n   \n    \n     \n  \n \n    \n  \n \n \n \n \n \n \n     \n   \n     \n    \n \n    \n  \n   \n    \n  \n    \n    \n    \n     \n    \n    \n   \n  \n   \n  \n    virus. These numbers do not capture the many more Americans who may not require \nhospitalization but suffer at home from this illness. Given the considerable increase in \nrespirato ry threats facing the older population over these past few years, the need for preventive \ntools to defend against them cannot be overstated. It is also worth noting that the majority of care is provided by women, with 1 in 4 women reporting being caregiver s and over a 1/3 of \nthese women reporting that they are caring for a parent and a parent in- law, according to the \nCDC. Caregiving is a challenging and demanding responsibility and involves spending an \nextensive amount of time with those caring more and can put older Americans at greater risk of \ncontracting a virus like RSV given the intergenerational aspect of a woman ’s caregiving roles. \nThat is why we are so encouraged to be here today speaking about not just 1 but 2 FDA-\napproved vaccines for this virus after decades of having no protection. This is truly an important \nstep forward and we are eager to share this committee’ s recommendations with our \ncommunities, so that all those who are eligible can benefit from this critical pr otection. \nHealthyWomen is grateful for this committee’ s work to ensure that these new protections are \nmade available to those most vulnerable to serious illness and death. We ask that you provide \nas clear and simple guidance as possible on who should consider receiving these vaccines \nbecause, as you know, that is not the final step before older Americans can access these \nvaccines. So, in order to ensure everyone who is eligible for the need of protection has broad \nand equitable access to the vaccine before the start of yet another respiratory season this Fall, \nwe ask for the process for publishing this guidance to be done in a timely and straightforward manner to ensure potential timely coverage by CMS. HealthyWomen appreciates the \nopportunity to address this important issue and we look forward to communicating the CDC ’s \nguidance to our communities so that everyone who is eligible for the vaccines understands the value they play in protecting their long -term well- being. Thank you. \nMichael Hoerge r, PhD, MSCR\nClinical Health PsychologistHealth Scientist and Health StrategistRuns a Health Science PhD Program \nThank you all for your service during this difficult time. I ’m Mike Hoerger . I run a Health Science \nPhD program in the D eep South. I ’m a Clinical Health Psychologist, Health Scientist , and Health \nStrategist. I ’m also in the sandwich generation with 3 young children at home and older relatives \nnearby. I have a few comments about COVID. We know from national wastewater data that \nSARS- CoV-2 transmission is lower now than during 75% of the pandemic, of course, higher \nthan 25% of the pandemic. But during this time of lower transmission, it ’s important for \norganizations and families to hopefully catch their breath and reflect on their COVID strategy. I \nappreciate how receptive you all were to oral comments last time. I have a few strategic \nsuggestions about COVID vaccines. First, transparency. I think we need more transparency and \nbalanced framing. We need to be clear on vaccine efficacy, while also acknowledging that \nbenefits wane substantially after 2 to 4 months , not annually , and they do less to protect against \nlong COVID than we might hope , with cumulative risk increasing upon each reinfection. My \nfamily is highly vaccinated, and we would get more today if possible, but we need to avoid \noverpromising on any particular tool. Second, agility. We need faster COVID vaccine updates \nbased on emerging variants so we’re skating to where the puck is going, not to where it was \nmonths ago. We need to open up Novavax to all Americans 6 months and older, regardless of \nvaccine history or ability to pay. We desperately need next- generation vaccines that \nsubstantially reduce transmission. Third, we need a multi -layered strategy. SARS- CoV-2 viral \nand aerosol particles linger in the air like smoke, infect people when inhaled, and can cause \nsevere damage to multiple organ systems. In addition to vaccines, we need to emphasize the use of high quality, well- fitting masks. Some of the best N95s are now only .09 cents each and \n35 \n \n   \n   \n     \n    \n \n  \n   \n     \n   \n      \n  \n    \n   \n \n \n  \n \n \n   \n    \n   \n    \n  \n      \n  \n   \n    \n     \n  \n   \n  \n     \n    \n   \n   \n     \n   \n \n   \n   \n  \n   \n   \n  \n    \n  \n \n   \n   \n  are readily available. We also need to emphasize the importance of air cleaning through \nventilation and filtration, particularly given the forthcoming ASHRAE building standards. Babies \nunder 6 months cannot mask or get COVID vaccines, so we need safe spaces in healthcare \nand at vaccination sites. A year ago, my twins were newborns and we had to navigate through a \nlarge health system to receive recommended medical care. W e passed 70 clinicians who were \nunmasked. That ’s extremely dangerous. We need masks in health and in dental care, \nparticularly for patients who must be unmasked at times for care. Finally, we need to do more \non outreach and education. Nationally, uptake of the bivalent booster has been lower than we would hope, and particularly so in my part of the country in the D eep South, often even among \nolder adults. We needed to reach out to the community, retail pharmacy chains , and clinicians. \nAgain, I appreciate you all working hard during the ongoing pandemic, particularly when you and your families may be dealing with illness, trauma, moral distress, bereavement , and other \nstressors. The work you are doing is very important. Thank you for your time. \nMs. Sarah BerryIndependent Pro-Vaccine Advocate \n42believer \nHello, CDC ACIP members. Thank you for your attention today. My name is Sarah Berry, also \nknown as 42believer online. I am an independent pro- vaccine advocate who splits my time \nbetween gathering critical information on anti -vaxxers for numerous journalists and volunteering \nmy time with pro -vaccine individuals and groups. One of them is Safe Communities Coalition, a \nnonprofit focused on educating legislators about vaccine policy issues, although there are many \nmore that I like to talk to when possible. My purpose in giving a comment today is to talk about \nthe stifling of innovation when anti -vaccine talking points embed themselves in the mainstream. \nWe see this in low uptake for flu vaccines, which aside from the HPV vaccine, were the most \ncommonly attacked vaccine prior to the pandemic. Some people, even those who I know \npersonally , have hesitations about the necessity of the flu shot. So, how do we reach the \naverage person about the flu vaccine? I have one talking point I use when speaking to friends \nwho are genuinely hesitant about the flu vaccine, which is to bring up a sadly not unheard of but \nvery serious consequence to flu infection, quadruple amputation. I recently, very recently, just \nyesterday , had a conversation with 2 friends about this and even shared pictures showing \nchildren as young as 5 needing this kind of intervention and they were absolutely shocked. Their \nfaces said everything. I think we’ ve gotten too used to seeing influenza triv ialized, partially \nbecause of COVID, partially because of anti- vaxxers prior to COVID, but many people do suffer \nor die from flu every year. We can save some of them by being more upfront about the dangers \nof not vaccinating against flu. Prior to the pandemic, anti -vaxxers also used fear about the flu \nvaccine to push a bill in my home state that would have banned flu vaccine requirements in healthcare facilities. The thorough discussions around all future vaccines that have been \ndiscussed today are eventually going to be stifled by the overtaking of anti- vaccine viewpoints, \nboth on a legislative level and a cultural one. As you all might have seen the fantastic Dr. Hotez , \nwho researches new vaccines without relying on typical pharmaceutical funding that anti-\nvaxxers hate so much, has faced attempts at having his innovation stifled by simply calling out \nthe influence of anti -vaccine talking points in our culture. This is my takeaway. We need to be \nmore specific. We need to be specific about what happens when people don’t vaccinate. We \nneed to show people examples and videos and feature these people, so they know that this is a real potential outcome, and we need more people like Dr. Hotez being specific about why anti-\nvaccine grifters should not be trusted. I’ve been following this topic since 2017. If you need help \nwith that, please reach out  at 42believer@gmail.com.  Thank you for your time. \n36 \n \n  \n  \n \n    \n    \n  \n   \n      \n    \n    \n     \n   \n    \n      \n   \n    \n      \n    \n   \n    \n    \n     \n    \n   \n   \n  \n    \n     \n  \n  \n   \n \n \n \n \n \n \n       \n   \n     \n    \n  \n    \n    \n  \n   \n  \n  Kelly Moore , MD, MPH\nChief Executive Officer \nGood afternoon. I'm Dr. Kelly Moore, the CEO  of Immunize.org and a former  ACIP member. \nImmunize.org is a 32 -year-old national nonprofit that supports implementation of ACIP \nrecommendations and advocates for health policies that remove barriers to immunization. It’s \ngreat to be at the threshold of having immunizations recomm ended to mitigate the under -valued \nburden of RSV disease in older adults and soon, hopefully , in infants. After today ’s vote, though, \nplease continue public updates to the ACIP early and often on effectiveness and safety. We \nneed evidence of the impact of these vaccines on the frail elderly in long- term care and \nelsewhere among the 80 plus population. In addition, as noted, the inflammatory neurologic \ndisease cases observed are, for now, an uninterpretable signal— maybe something, maybe not. \nEither way, confidence in implementation will be helped by regular updates as you learn more. \nAs an aside, it is notable to me that the debate between shared clinical decision- making and \nroutine recommendation seems to weigh more than usual on Medicare logistics and less on the \ninterpretation of efficacy and safety data, and also that today ’s decision must be made without \nthe final prices. That issue at least seems fixable. After today ’s votes comes the need to \naddress RSV in infants. We’ll have to work fast to make a difference for babies this fall, and I \nurge the committee and the CDC to make decisions concerning maternal vaccination and infant \nimmunization as soon as feasible and to publish an MMWR without delay. Timing is going to be \na crunch. In addition, we want affordable infant RSV protection to be within the reach of every family. To that end, if judged an effective use of resources by ACIP, we encourage you to vote \nto include the new long- acting monoclonal antibodies , or mAbs , in the VFC program so \nnewborns  are not denied access due to a family ’s inability to pay. Thank you to those working to \nupdate our regulatory policy making payment processes to support the use of passive \nimmunization for population health. Experts like Vanderbilt ’s Jim Crowe tell me t hat long acting \nmAbs could be the quickest tool to make to protect the population from the next pandemic virus, beating vaccines by months. In light of that, now is a great time to standardize the process to evaluate, approve , and recommend passive immuniz ations with population- wide application and \nto establish the expectation that they, like active vaccinations, should be affordably accessible to all in the interest of public health. Thank you for all your hard work today. I miss you. \nTHURSDAY:  JUNE 2 2, 2023  \nAGENCY UPDATES \nCenters for Disease Control and Prevention \nJosé R. Romero, MD noted that throughout this meeting, the ACIP would receive the most \ncurrent and comprehensive information on many of CDC ’s efforts, so he would keep his CDC \nupdates  brief and only share high- level updates on COVID -19, influenza, measles , and efforts to \nmaintain childhood vaccination coverage. COVID -19 remains a key public health priority. \nCOVID -19 hospitalizations and deaths continue to decline from the seasonal peak of January \n2023. These peaks were far lower than those seen during the 2 previous winters. CDC provides \nweekly updates on COVID- 19 vaccine distribution and administration on the CDC COVID -19 \nTracker website. As of June 11, 2023, greater than 56 million individuals have received an \nupdated bivalent COVID -19 vaccine dose. Since the recommendation of the Pfizer- BioNTech \nCOVID -19 vaccine for children aged 5─ 11 years, greater than 9 million individuals aged 5─ 11 \nyears have completed the primary series. While most Americans continue to pay nothing out -of-\npocket for COVID -19 vaccine due to their insurance coverage, 25 million uninsured American \n37 \n \n  \n   \n  \n   \n  \n  \n  \n     \n  \n      \n    \n     \n     \n  \n \n   \n  \n     \n   \n \n  \n     \n  \n  \n    \n    \n  \n   \n    \n \n \n  \n \n   \n \n   \n   \n     \n    \n   \n \n  \n     \n   \n  adults are at risk of losing access to affordable vaccines for COVID -19 and treatments when \nthese transit ion to the commercial marketplace. In April 2023, HHS announced the Bridge \nAccess Program for COVID -19 vaccines and treatment. This public -private partnership provides \nunder -and un -insured adults with access to COVID -19 vaccines and treatments at no cost from \nFall 2023 to the end of 2024. Turning now to seasonal influenza, following a moderately severe \ninfluenza season that peaked earlier than usual in late fall and early winter, influenza \nvaccination provided substantial protection this season. CDC again partnered with the Ad \nCouncil and the American Medical Association (AMA) for their annual “Get My Flu Shot” \nCampaign. The campaign encouraged the American public, with an emphasis on Black and \nHispanic audiences, to get vaccinated against the influenza for the season 2022- 2023 . Planning \nfor a new campaign for the 2023- 2024 season is underway. With regard to avian influenza, the \ncurrently circulating influenza A(H5) viruses remains low. However, CDC and others remain \nvery vigilant for this. An A(H5) candidate vaccine was developed by CDC and made available to \nvaccine manufacturers in early 2022. CDC continues to work with international, national, state \nand local partners to detect H5, and to prevent transmission through enhanced surveillance and \nguidance for people who may be exposed to infected birds. CDC continues to analyze viral sequence data for genetic markers associated with greater disease severity, more efficient \ninfectivity , transmissibility to humans, reduced susceptibility to antiviral drugs, and impact on \ncandidate vaccines and diagnostics. With regard to measles, with declines in measles \nvaccination rates globally during the COVID -19 pandemic, measles outbreaks are occurring in \nall World Health Organization regions. The United States has seen an increase in measles cases from 49 in 2021 to 121 in 2022. All have occurred among children who are not fully \nvaccinated, including the outbreaks in Minnesota and Ohio. Jurisdictions at highest risk for \nmeasles continue to be those contained communities with persistently low vaccination coverage and importations from locations with measles outbreaks. In terms of CDC’s current efforts to \nmaintain childhood vaccination coverage, the agency launched the “ Let’s Rise Campaign” to \naddress pandemic -related declines in routine immunizations and equip partners and health care \nproviders with actionable strategies, resources , and data to support getting all Americans back \non schedule with their routine immunizations. More information about “Let’s Rise ” and access to \nroutine immunization resources and data can be found on CDC ’s website. \nCenters for Medicare and Medicaid Services \nMary Beth Hance reported that a CMS continues to emphasize the importance of routine \npediatric immunizations. One way they have done this is th rough the Connecting Kids to \nCoverage National Campaign, which provides materials that can be used or rebranded to \noutreach grantees and a variety of partners who include government agencies, community \norganizations, health care providers, schools , and others. There are many tools available \nrelated to vaccines on the Connecting Kids to Coverage National Campaign. In addition, a \nBack -to-School  webinar was held on Tuesday of this week that emphasized, among other \nthings, the importance of immunizations and of getting caught up on immunizations before \nschool. Shifting to follow -up from the previous day’s adult RSV vaccines conversation, Ms. \nHance confirmed f rom her colleagues on the Medicare side of CMS that if this vaccine is \nrecommended, it will be included in Part D of the Medicare Program. \n38 \n \n   \n \n    \n  \n  \n       \n     \n   \n     \n   \n     \n    \n     \n     \n    \n   \n    \n  \n  \n    \n    \n    \n   \n   \n    \n \n    \n    \n   \n    \n      \n  \n \n \n \n    \n  \n \n     \n  \n  \n  \n   \n \n    \n    \n    \n  \n Food and Drug Administration \nDavid Kaslow, MD reported that since the February 2023 ACIP meeting , 2 RSV vaccines with \nproposed indications for use in adults 60 years of age and older were reviewed by Vaccines and \nRelated Biological Products Advisory Committee (VRBPAC) , which subsequently approved both \nin May 2023. In addition, VRBPAC also met to review an RSV vaccine with the proposed \nindication for the prevention of lower respiratory tract disease and severe lower respiratory tract disease caused by RSV in infants from birth through 6 months of age by active immunization of \npregnant individuals. Also reviewed by ACIP the previous day were VRBPAC ’s \nrecommendations in March on the selection of strains to be included in the influenza virus \nvaccines for the 2023- 2024 influenza season. In April, FDA amended the Emergency Use \nAuthorizations ( EUAs ) of the 2 COVID -19 bivalent mRNA vaccines to simplify the vaccination \nschedule for most individuals and to authorize the current bivalent vaccine containing original \nand Omicron BA.4 and BA.5 strains for all doses administered to individuals 6 months of age \nand older. A week ago, VRBPAC met to discuss and make recommendations on the selection \nof strains to be included in the periodic updated COVID -19 vaccines for the 2023- 2024 \nvaccination campaign. The committee unanimously voted to update the vaccine composition to \na monoval ent COVID -19 vaccine with an Omicron XBB lineage and expressed a preference for \nthe XBB.1.5 sublineage. On June 16, 2023 , FDA advised manufacturers who will be updating \ntheir COVID -19 vaccines that they should develop a vaccine with a monovalent XBB.1.5 \ncomposition for the 2023 -2024 formula of COVID- 19 vaccines in the US. In April 2023, FDA co -\nhosted with Biomedical Advanced Research and Development Authority (BARDA ) a workshop \non recombinant protein- based COVID -19 vaccines to review and discuss overcoming \nchallenges faced by recombinant protein vaccine platforms in timely strain updates and pandemic readiness. Highlighted in that workshop was the timely availability of additional \nupdated COVID -19 vaccines beyond the current nucleic acid- based vaccines approved for use \nat the onset of periodic vaccination campaigns. A number of regulatory actions are anticipated \nin the coming months. As reflected in the current ACIP meeting agenda, the magnitude of the \ncurrent submissions under review is unprecedented. On behalf of FDA’s Office \nof Vaccines Research and Review (OVRR) and Center for Biologics Evaluation and Research \n(CBER), Dr. Kaslow thanked the ACIP and the many ACIP WGs for their partnership in the work \non this very large portfolio vaccine and vaccine candidates. \nHealth Resources and Services Administration \nCDR Reed Grimes, MD, MPH reported that the National Vaccine Injury Compensation \nProgram (VIPC) continues to process a high volume of claims in Fiscal Year 2023. As of June \n1, 2023, petitioners have filed 747 claims with the VICP and $119.6 million has been awarded, including awards to petitioners for their attorney fees and costs. In addition, the VICP is \nworking on a backlog of 1,363 claims alleging vaccine injury. More data about the VICP can \nbe obtained at www.hrsa.gov/vaccinetackcompensation/data/index.html . As of June 1, 2023, \n11,806 claims alleging injuries or death from COVID- 19 countermeasures have been filed with \nthe Countermeasures Injury Compensation Program (CICP), including 8,372 claims alleging \ninjuries from COVID -19 vaccines. CICP has rendered decisions on 919 COVID -19 clai ms. Of \nthe countermeasures claims, 25 have been determined medically eligible for compensation, \n20 claims are pending a review of the eligible expenses , 4 have been compensated, and 1 did \nnot have eligible expenses for reimbursement. A total of 894 COVID -19 countermeasure \nclaims have been denied compensation because of various reasons. More information about \nthe CICP can be found at www.hrsa.gov/CICP . \n39 \n \n  \n \n    \n   \n   \n \n  \n  \n   \n  \n  \n \n \n   \n  \n  \n \n \n   \n   \n \n \n \n \n     \n    \n     \n  \n   \n  \n   \n    \n        \n  \n   \n   \n    \n   \n   \n    \n    \n   \n      \n   \n   \n     \n  \n    \n    Indian Health Service \nMatthew Clar k, MD, FAAP, FACP reported that the IHS continues to prioritize access, \nquality, and equity in vaccine distribution and administration for American Indian and Alaska \nNative tribal communities served by the IHS system of care. Following expiration of the Public \nHealth Emergency (PHE), the IHS has remained committed to its efforts to promote COVID-19 vaccination in all age groups in every region. They are currently implementing a national \nvaccine strategy for the tribal communities served by IHS federal, tribal, and urban Indian \norganization programs. The E3 Vaccine Strategy is designed to promote access for every \npatient at every encounter to every recommended vaccine when appropriate. This includes all \nACIP -recommended vaccines in all age groups. Working in collaboration with key \nstakeholders, especially its tribal and urban Indian organization partners, IHS is committed to \nimproving general vaccination rates in tribal communities. The E3 Operational Plan includes a \nbottom -up approach to encourage innovation, incentivize effort, and recognize success \ndrawing on the adaptability of the IHS’s comprehensive health care system to cross -pollinate \nfederal, tribal, and urban Indian programs using best practices developed in Indian country for \nIndian country. Following rollout of the E3 Champions Pilot Program in Spring 2023, Dr. Clark \nsaid he was pleased to report that over 2 dozen federal, tribal, and urban Indian programs have applied for and received designation as an IHS E3 Champion Pilot site. IHS look s \nforward to continued collaboration with its tribal, urban, and federal partners to ensure access to safe and effective vaccines and to reduce morbidity and mortality from vaccine- preventable \nillness across the age spectrum for American Indian and Alaska Native people served by the IHS. \nNational Institutes of Health \nJohn Beigel, MD reported that the NIH continues to support basic and clinical research to \nimprove human health. A large part of what the NIH does is centered around new and better \nvaccines , for which he highlighted a few studies and other updates that may be of interest to \nACIP. For COVID -19, although currently available vaccines are highly effective at preventing \nsevere disease, infection and death, there is significant interest in mucosal vaccines that could \npotentially reduce transmission of the virus and/or asymptomatic disease. In November, the \nNational Institute of Allergy and Infectious Diseases (NIAID ) co-hosted a workshop on the \nscience of developing mucosal vaccines for SARS -CoV-2. The workshop highlighted what is \nknown, gaps in the field, and a potential path forward. A link to the manuscript that summarizes \nthe workshop will be provided in the written comments. Related to the need for advancing next \ngeneration vaccines, Project NextGen was announced in May 2023 . Project NextGen is a \ncoordinated effort through which NIAID and BARDA will work with the private sector to advance \na pipeline of new innovative vaccines into clinical trials. NIAID ’s efforts are going to focus on a \nstructured program evaluating multiple next -generation COVID -19 vaccines in Phase 1 and \nPhase 2 clinical trials. A link will be provided in the written comments, but it can also be found \njust by searching “NIAID Project NextGen.” Shifting to tuberculosis (TB), a clinical trial testing a \nfreeze -dried, temperature- stable TB vaccine was found to be safe and effective in simulated \nantibodies, as well as the cellular immune response. A non- stable temperature form had \npreviously been studi ed, but this is the first time any subunit TB vaccine in a temperature -stable \nform has been evaluated, which is critical in terms of thinking about how to roll out a TB vaccine. \nFor influenza, a clinical trial of an experimental mRNA universal influenza vaccine developed by \nNIAID ’s Vaccine Research Center (VRC) began enrolling volunteers at Duke. This is the first \ninvestigational universal influenza vaccine candidate tested by the Collaborative Influenza \nVaccine Innovation Center (CIVIC ) Program, which is a program to advance more durable, \nbroadly protective and longer lasting influenza vaccines. The approval of RSV vaccines marks \n40 \n \n    \n     \n    \n    \n   \n    \n     \n   \n   \n    \n \n     \n \n \n \n \n     \n      \n       \n \n  \n \n  \n   \n \n \n \n \n \n      \n \n  \n    \n      \n    \n     \n   \n     \n   \n      \n   \n   \n       \n            \n  \n  \n \n \n an important step toward protecting the nation from this serious respiratory disease. It is \nimportant to highlight that that accomplishment is a result of decades of scientific discovery and \nresearch funded by the NIH and many other groups. The development of effective vaccines \ntakes time. It is a series of incremental discoveries and steps, but good science is fundamental \nto ge tting effective vaccines like the ACIP voted on the previous day . For HIV, May 18, 2023 \nmarked 26th anniversary of HIV Vaccine Awareness Day . An effective, safe, long- lasting HIV \nvaccine remains crucial for ending the HIV pandemic worldwide. However, HIV c ontinues to \npose a formidable challenge to vaccine development due to its ability to mutate rapidly and \nheighten reservoirs that the immune system cannot reach. The NIH applauds efforts of the \nglobal community of scientists, advocates, study participants, and funders enabling \nunprecedented levels of innovation and adaptation in pursuit of a highly effective HIV vaccine. \nThere are several other updates and links for which he referred listeners to the written \ncomments. \nOffice of Infectious Disease and HIV/AI DS Policy \nCDR Valeria Marshall, MPH, PMP reported that in the National Vaccine Program , housed \nwithin the Office of Infectious Disease and HIV/AIDS Policy (OIDP), is working on the progress \nreport for the “Vaccines Federal Implementation Plan” and will work with federal agencies over \nthe summer to provide their progress across goals and strategies. The National Vaccine Advisory Committee (NVAC) convened on June 16- 17, 2023. In an effort to be responsive to \nemerging challenges and immunization, select agenda topics included preparing for the \npotential approval of passive immunization products, restoring vaccination rates in the post -\npandemic period, and address ing clinician fatigue. The committee updated their progress on 2 \nongoing charges, includ ing the charge on vaccine innovations and vaccine safety. \nPNEUMOCOCCAL VACCINES \nIntroduction \nKatherine A. Poehling, MD, MPH (ACIP WG Chair) reminded everyone that pneumococcal \nvaccines currently recommended for use in the US include PCV13 and PCV20 for adults . \nPCV13 and  PCV15 are recommended for children . PPSV3 has a risk -based recommendation \nfor children. PPSV3 is recommended for adults who previously received PCV13 or PCV15, but \nnot for those receiving PCV20 20. The goal is to move forward with fewer differences. As a \nreminder, all children under 2 years of age have the same pneumococcal vaccine \nrecommendation for 3 primary series and a booster, often known as the 3 + 1 sch edule. The \nprimary series doses are administered at 2, 4, and 6 months and the booster is given at 12 to 15 \nmonths later. Currently, either PCV13 or PCV15 can be given to US children. Children with \ncertain underlying conditions are recommended to receive P PSV23 . Children with chronic \nmedical conditions (CMC), cerebrospinal fluid (CSF) leak, and cochlear implants are \nrecommended to receive PPSV23 ≥8 weeks after the conjugate vaccine. Children with \nimmunocompromising conditions are recommended to receive PPSV23 ≥8 weeks after the \nconjugate vaccine. Then ≥5 years later , a second dose of PPSV23 is recommended . Children \n6─8 years of age with CMC can receive PPSV23 if they did not receive pneumococcal \nconjugate vaccine. Of note, CMC includes chronic heart disease (CHD), chronic lung disease \n(CLD),and diabetes mellitus (DM) . \n41 \n \n  \n       \n    \n   \n  \n \n \n     \n \n   \n        \n \n   \n   \n \n \n   \n   \n \n     \n \n \n \n   \n \n    \n \n \n   \n  \n \n \n    \n \n    \n    \n  \n \n          \n   \n         \n        \n \n \n  An extended indication for PCV20 use among children was approved on April 27, 2023. Pediatric PCV15 use was approved in June 2022 . Both PCV15 and PCV20 were approved \nbased on safety and immunogenicity data compared with PCV13. There are no direct PCV15 vs \nPCV20 comparisons. Unknown clinical implications include numerically lower antibody \nresponses vs PCV13 and numerically higher antibody response against serotype 3 in PCV15 vs PCV13 . \nWith all of this in mind, the WG consider ed the following policy questions: \nShould PCV20 be recommended as an option for pneumococcal conjugate vaccination according to currently recommended dosing and schedules for US children aged <2 years ? \nShould PCV20 without PPSV23 be recommended as an option for pneumococcal \nvaccination for US children aged 2 ─18 years of age with underlying medical conditions that \nincrease the risk of pneumococcal disease? \nPresentations during this session focused on and economic analysis and public health impact of \nPCV20 use in children presented by Dr. Charles Stoecker (Tulane University) ; a comparison of \ncost- effectiveness analyses on PCV20 use in children by Dr. Ayabina Diepreye (CDC/NCIRD) ; \na summary of the WG’s interpretation on EtR and policy options presented by Dr. Miwako \nKobayashi (CDC/NCIRD) ; the VFC Resolution presented by Dr. Jeanne Santoli (CDC/NCIRD); \nand the following 5 votes: \nVote #1: Routine PCV Use for All Children aged <24 Months \nMiwako Kobayashi, MD, MPH (CDC/NCIRD) displayed and read the proposed vote language \nfollowing the public comment period. The vote was combined with the Pneumococcal Vaccine \nSession for ease of reading: \nUse of either PCV15 or PCV20 is recommended for all children aged 2– 23 months \naccording to currently recommended PCV dosing and schedules. \nMotion/Vote #1: Routine PCV Use for All Children aged <24 Months \nDr. Cineas made a motion to approve the recommendation as stated, which Ms. Bahta \nseconded. No COIs were declared. The motion carried with 14 affirmative votes, 0 negative \nvotes, and 0 abstentions. The disposition of the vote was as follows: \n14 Favored: Bahta, Bell, Brooks, Chen, Cineas, Daley, Kotton, Lee, Loehr, Long , McNally, \nPoehling, Sanchez, Talbot \n0 Opposed: N/A \n0 Abstained: N/A \n42 \n \n     \n  \n \n    \n \n \n \n  \n  \n   \n \n      \n     \n    \n     \n   \n    \n   \n \n \n   \n  \n \n      \n     \n    \n \n          \n   \n         \n        \n \n \n \n  \n  \n \n    \n \n \n   \n \n         \n  \n \n  \n  \n  Vote #2: Catch -Up PCV D oses for Children Aged 24– 71 Months with an Incomplete PCV \nVaccination Status \nMiwako Kobayashi, MD, MPH (CDC/NCIRD) displayed and read the proposed vote language \nfollowing the public comment period. The vote was combined with the Pneumococcal Vaccine \nSession for ease of reading: \nFor children with an incomplete PCV vaccination status, use of either PCV15 or PCV20 according to cu rrently recommended PCV dosing and schedules for: \n• Healthy children aged 24 ─59 months \n• Children with specific risk conditions* aged 24─ 71 months \n*Risk conditions include: cerebrospinal fluid leak; chronic heart disease; chronic kidney disease (excluding mai ntenance \ndialysis and nephrotic syndrome, which are included in immunocompromising conditions); chronic liver disease; chronic \nlung disease (including moderate persistent or severe persistent asthma); cochlear implant; diabetes mellitus; \nimmunocompromising conditions (on maintenance dialysis or with nephrotic syndrome; congenital or acquired asplenia or \nsplenic dysfunction; congenital or acquired immunodeficiencies; diseases and conditions treated with immunosuppressive \ndrugs or radiation therapy, including malignant neoplasms, leukemias, lymphomas, Hodgkin disease, and solid organ \ntransplant; HIV infection; and sickle cell disease and other hemoglobinopathies). \nMotion/Vote #2: Catch -Up PCV Doses for Children Aged \n24–71 Months with an Incomplete PCV Vacci nation Status \nDr. Daley made a motion to approve the recommendation as stated, which Dr. Long seconded. \nNo COIs were declared. The motion carried with 14 affirmative votes, 0 negative votes, and 0 \nabstentions. The disposition of the vote was as follows: \n14 Favored: Bahta, Bell, Brooks, Chen, Cineas, Daley, Kotton, Lee, Loehr, Long, McNally, \nPoehling, Sanchez, Talbot \n0 Opposed: N/A \n0 Abstained: N/A \nVote #3: Children Aged 2– 18 Years with Any Risk Condition Who Have Completed Their \nRecommended PCV Doses Before Age 6 Years \nMiwako Kobayashi, MD, MPH (CDC/NCIRD) displayed and read the proposed vote language \nfollowing the public comment period. The vote was combined with the Pneumococcal Vaccine \nSession for ease of reading: \nFor children aged 2–18 years with any risk condition who have received all recommended doses before age 6 years: \n• Using ≥1 dose of PCV20: No additional doses of any pneumococcal vaccine are \nindicated. This recommendation may be updated as additional data become \navailable. \n• Using PCV13 or PCV15 (no PCV20): A dose of PCV20 or PPSV23 using \npreviously recommended doses and schedule is recommended. \n43 \n \n  \n \n    \n  \n \n     \n     \n   \n \n          \n   \n         \n        \n \n \n    \n \n \n   \n \n \n    \n \n   \n  \n \n \n   \n \n \n   \n    \n  \n \n          \n   \n         \n        \n \n \n \n \n    \n \n \n  \n  Motion/Vote #3: Children Aged 2– 18 Years with Any Risk Condition\nWho Have Completed Their Recommended PCV Doses Before Age 6 Years \nDr. Long made a motion to approve the recommendation as stated, which Ms. Bahta seconded. \nNo COIs were declared. The motion carried with 14 affirmative votes, 0 negative votes, and 0 \nabstentions. The disposition of the vote was as follows: \n14 Favored: Bahta, Bell, Brooks, Chen, Cineas, Daley, Kotton, Lee, Loehr, Long, McNally, \nPoehling, Sanchez, Talbot \n0 Opposed: N/A \n0 Abstained: N/A \nVote #4: Children Aged 6– 18 Years with A ny Risk Condition Who Have Not Received Any \nDose of PCV \nMiwako Kobayashi, MD, MPH (CDC/NCIRD) displayed and read the proposed vote language \nfollowing the public comment period. The vote was combined with the Pneumococcal Vaccine \nSession for ease of reading: \nFor children aged 6–18 years with any risk condition who have not received any dose of \nPCV13, PCV15, or PCV20, a single dose of PCV15 or PCV20 is recommended at least 8 weeks after the most recent dose of pneumococcal vaccine. When PCV15 is used, it \nshould be followed by a dose of PPSV23 at least 8 weeks later if not previously given. \nMotion/Vote #4: Children Aged 6– 18 Years with Any\nRisk Condition Who Have Not Received Any Dose of PCV \nDr. Sánchez made a motion to approve the recommendation as stated, which Dr. Daley \nseconded. No COIs were declared. The motion c arried with 14 affirmative votes, 0 negative \nvotes, and 0 abstentions. The disposition of the vote was as follows: \n14 Favored: Bahta, Bell, Brooks, Chen, Cineas, Daley, Kotton, Lee, Loehr, Long, McNally, \nPoehling, Sanchez, Talbot \n0 Opposed: N/A \n0 Abstained: N/A \nVote #5: VFC Resolution \nJeanne Santoli, MD, MPH (CDC/NCIRD) displayed and read the proposed vote language \nfollowing the public comment period. The vote was combined with the Pneumococcal Vaccine \nSession for ease of reading: \nApprove the Vaccines for Children (VFC) resolution for pneumococcal pneumonia. \n44 \n \n  \n \n    \n \n    \n    \n  \n \n          \n   \n         \n        \n \n \n \n \n \n \n \n     \n  \n  \n   \n   \n     \n   \n \n \n \n \n \n    \n    \n    \n   \n \n \n \n \n \n \n  \n   \n    \n   \n   \n    \n Motion/Vote #5: VFC Resolution \nMs. Bahta made a motion to approve the recommendation as stated, which Dr. Sánchez \nseconded. No COIs were declared. The motion carried with 14 affirmative votes, 0 negative \nvotes, and 0 abstentions. The disposition of the vote was as follows: \n14 Favored: Bahta, Bell, Brooks, Chen, Cineas, Daley, Kotton, Lee, Loehr, Long, McNally, \nPoehling, Dr. Sánchez , Talbot \n0 Opposed: N/A \n0 Abstained: N/A \nDENGUE VACCINE \nBrief Summary \nThe Dengue Vaccines schedule included a session introduction by Dr. Wilbur Chen (ACIP, WG \nChair) ; introduction of policy questions for TAK- 003 by Dr. Alfonso Hernandez (CDC/NCEZID); \npresentation of a c ost-effectiveness analysis and the health impacts of routine vaccination with \nTAK- 003 dengue vaccine in Puerto Rico by Dr. Guido Espana (University of Notre Dame) ; a \nsummary of two economic models for dengue vaccine TAK- 003 use in Puerto Rico by Dr. \nRajReni Kaul (CDC/NCIRD) ; and a presentation of the partial EtR framework for TAK -003 by Dr. \nJoshua Wong (CDC/NCEZID) . No votes were taken on this topic during this meeting. \nCHIKUNGUNYA VACCINE \nBrief Summary \nThe C hikungunya Vaccine session included a session introduction by Dr. Beth Bell (ACIP, WG \nChair); a presentation on the value of chikungunya vaccine to US travelers and providers by Ms. \nNicole Lindsey (CDC/NCEZID) ; and presentations on chikungunya virus infection among \nlaboratory workers , a large chikungunya outbreak in Paraguay , and WG plans and timelines by \nDr. Susan Hills (CDC/NCEZID) . No votes were taken on this topic during this meeting. \nRESPIRATORY SYNCYTIAL VIRUS VACCINES: PEDIATRIC/MATERNAL \nBrief Summary \nThe Respiratory Syncytial Virus Vaccines : Pediatric/Maternal session included a session \nintroduction by Dr. Sarah Long (ACIP, WG Chair); a presentation on an economic analysis of \nRSVpreF in pediatric populations by Dr. David Hutton (University of Michigan); a presentation \non the EtR of Pfizer maternal RSV vaccine by Dr. Katherine Fleming -Dutra (CDC/NCIRD);  a \npresentation on an economic analysis of the comb ined use of nirsevimab and maternal \nRSVpreF vaccine by Dr. David Hutton (University of Michigan); and a presentation on c linical \nconsiderations for RSV maternal vaccine and nirsevimab by Dr. Jefferson Jones (CDC, NCIRD) . \nNo votes were taken on this topic during this meeting. \n45 \n \n  \n \n    \n     \n \n \n   \n \n   \n     \n  \n    \n \n \n  \n \n  \n      \n    \n   \n \n  \n     \n   \n  \n    \n \n \n  \n   \n      \n   \n     \n   \n     \n    \n     \n    \n  \n  \n   \n  \n  \n   \n    \n     \n    \n  PUBLIC COMMENTS \nThe floor was opened for public comment on June 22, 2023 at 4:50 PM ET. Given that many \nmore individuals registered to make oral public comments than could be accommodated during \nthis meeting, selection was made randomly via a lottery. Dr. Lee provided a gentle reminder that \nthe ACIP appreciates diverse viewpoints that are respectful in nature and issue- focused rather \nthan comments directed at individuals. The comments made during the meeting are included in \nthis document. Members of the public also were invited to submit written public comments to \nACIP through the Federal eRulemaking Portal under Docket Number ID CDC -2023- 0035. Visit \nhttp://www.regulations.gov for access to the docket or to submit comments or read background \ndocuments and comments received. The public comment session occurred prior to the votes, \nbut the votes were connected back with their respective sessions for ease of reading. \nMr. Joaquín Beltrán\nBiden/Harris 2020 Regional Director\nSmall Retail Investor of Novavax V accine \nThank you for having me. Full transparency, I was a Biden/Harris 2020 Regional Director and \ncurrently am a small retail investor of Novavax vaccine’ s ongoing availability, vaccinated with 2 \nPfizers , 1 Novavax , and never had COVID. My name is Joaquín Beltrán . Today I am calling on \nthe CDC to fulfill its specific mission to control and prevent disease. Here are the specific \nactions to take: 1) make Novavax ’s updated XBB .1.5 booster available upon manufacturing \ncompletion; 2) update booster guidelines for equal access and allow for multiple boosters to \nimprove protection; 3) expand Novavax access to everyone 6 months and up; 4) bring back \nmask requirements in healthcare savings ; and 5) bring back testing and data. Here are some \nstories on why these actions are important. My friend Robbie, who has been suffering from long-\nCOVID for years, her mother was recently in the hospital for a non -COVID issue . She acquired \nCOVID in the hospital and died from that very infection—a tragic and preventable death. My \ngrandma and my dad, who both have long COVID, my grandma for whom I am a caregiver — \nthey have been experiencing long- COVID after their infections. Both have circulation issues and \ntheir quality of life has not been the same. Other friends, in trying to protect themselves, many \nhave had to lie or go out of state , or the country even, to obtain a Novavax vaccine because of \ncurrent language in the guidelines, specifically the line that reads, “but have not previously \nreceived a COVID -19 booster and if they cannot or will not receive mRNA vaccines. ” This \nlanguage should be removed immediately. Other friends have lost all sources of income due to \ndisability and others are currently in this very moment being evicted from their homes because \nof long- COVID. These stories are not unique to people I know. Millions are suffering and going \nthrough this suffering from long- COVID and through this financial hardship. Moreover, hospitals \nare collapsing from shortages, from thousands of healthcare workers who have died from \nCOVID , many more who have become disabled, and from increased overall morbidity in the \npopulation from the CDC ’s de facto mass reinfection policy that creates cumulative risk — \ncumulative risk of heart attacks, stroke, brain damage, Type 1 diabetes in children, immune \ndysregulation, and much more. I am urging the CDC to take immediate action to protect our \nfamilies and communities by : 1) making Novavax ’s updated XBB .1.5. booster available upon \nmanufacturing completion; 2) updating booster guidelines for equal access and allow for \nmultiple boosters to improve protection ; 3) expanding Novavax access to everyone 6 months \nand older ; 4) bringing back mask requirements in healthcare settings; and 5) bringing back \ntesting and data. Thank you so much for your time. \n46 \n \n  \n \n \n \n   \n      \n  \n      \n    \n \n    \n    \n    \n  \n    \n   \n     \n    \n   \n  \n      \n \n     \n       \n   \n  \n \n  \n   \n   \n    \n      \n  \n  \n  \n  \n   \n    \n \n  \n \n \n    \n   \n   \n    \n    \n    \n   \n       \n      Dorit Reiss, JD , PhD \nProfessor of Law \nUniversity of California San Francisco \nHello, my name is Dorit Reiss. I am a Professor of Law at UC San Francisco. T hank you for the \nopportunity to again comment to the committee. I have 3 points to make first following the \ncommittee’ s careful critical discussion of RSV vaccines both yesterday and today, the \npenetrating question about the data, and the thoughtful way of the discussion. Frist, I’d like to \nthank both the committee and the WGs for their extensive work on this. This meeting always \nshow s the extensive data and work behind every vaccine decision, with reams of information \nprovided, though you have to boil it down to relatively short presentation. M ore than ever, I think \nthis meeting shows us how hard it is to make decisions when you don’ t have full information, \nwhich you rarely do, but this is a little more extreme than usual. It’s exactly in this situation \nwhere we need the expert input of a committee like ACIP even more than when the data is \nclear. I’d like to reinforce the committee members ’ comments that we need data before the \ncommittee gets to a vote, but I would like to finish by rem inding the committee and CDC on this \npoint that the vaccine- recommended under “ shared clinical decision- making” may be treated by \ndoctors as less important and not recommended. I hope that any materials sent out will remind \ndoctors of the risk of the diseases and vaccines they ’re recommending for in this way and set \nout clearly that at least a discussion of the vaccine is recommended. The shared clinical \ndecision- making shouldn ’t be “don’t talk about it, ” but should be “at least talk about it. ” Second, \nsince we discuss ed dengue and chikungunya vaccine today, and following yesterday ’s \ndiscussion of the reemergence of polio, I want to use those to remind everyone of the \nimportance o f covering these diseases and looking for the safety of the citizens of our territories \nas much as of the states, and generally, the importance of addressing so- called neglected \ntropical diseases , which are not really tropical , including by funding and promoting vaccination \nagainst them. Thank you for highlighting the larger burden of these outbreaks both in deaths and in other ways they are harming, and of course, in this age of climate change and travel, diseases don’ t stay. They will be coming beyond their borders, and we need to look at them for \nmore selfish reasons as well. A bit off topic, this is a chance to remind everyone of the \nimportance of protecting our vaccine scientists from harassment. To build on this last point, I \nwant to remind people that although anti -vaccine harassment has always been part of the reality \nof people responding to this information, as several of our scientists can testify, it’s been going \nmore extreme, more virulent, and the volume has grown. Although CDC and ACIP have an \nimportant role in providing good information, they ’re not going to be in the front of line of \ndebunking. But I hope CDC makes sure that its scientists and ACIP expert s have the support \nand protection they need to do the job safely and with resources and ans wers when harassed , \nand I would encourage other institutions to support scientists to speak up as well. Thank you. \nPatricia Neuenschwander, PNP \nPediatric Nurse Practitioner Good evening. I would love to stand before you and commend this committee on their rigorous \nevaluation of high- quality studies used to make recommendations, but I can’ t. I am a nurse who \nwas a defender of vaccine safety and efficacy, a nurse who dutifully vaccinated her children and \nherself, confidently trusting that t he CDC recommendations were based on a rigorous \nevaluation of high- quality studies. I now know that was a lie. I sat yesterday listening to Dr. \nTalbot express her legitimate concerns over the RSV studies. When those concerns were not \naddressed, she did not vote “no.” She abstained. This is not scientific discourse. It is a pressure \ncooker for experts in the field to vote unanimously for anything that is put forward giving the \nillusion of consensus. I want to focus the remainder of my comments specifically on the \n47 \n \n   \n   \n  \n     \n  \n \n    \n   \n     \n   \n    \n   \n  \n  \n    \n   \n \n  \n  \n    \n   \n \n \n \n \n \n  \n     \n     \n \n   \n   \n   \n    \n     \n    \n \n     \n      \n    \n     \n    \n     \n \n  \n   \n    \n    \n  inadequate RSV vaccine science used yesterday and that is being used today with pregnant \nwomen. They did not study the people who would potentially benefit —people over 75, nursing \nhome patients, patients with the usual amount of comorbid conditions, or the immune \ncompromised. Applying the questionable data from one healthy group to another group that has \nfar more risk and yet not studied, is scientifically unsound. Immunogenicity trials are inadequate. \nThere are no established immune correlates of protection. We know nothing about additional \ndoses or the coadministration with vaccines other than a small number who received a flu \nvaccine. The factual evidence presented from the GRADE evaluations did not show benefit with \nhospitalization, severe illness , or death, probably because the population used was healthy. We \nwill never know now, but I ’m sure that you will use suboptimal , biased observational studies in \nthe future to try and show it does. The actual science show s that it may reduce hospitalization \nfor RSV illness, but the effect is very uncertain and a very low -evidence type. It may impact \nsevere RSV illness requiring supplemental oxygen and other support, but the effect is very \nuncertain and a very low -evidence type. Yet you’ ll tell providers and the American people that it \nprevents severe disease and hospitalizations. These issues are not unique to the RSV vaccine \ntrials. I have watched again and again as ACIP gave blanket approvals to COVID vaccines and \nboosters with equally questionable data. This is why you have anti-vaxxers. You are losing \ncredibility and trust with frontline healthcare workers, and you have lost credibility and trust with \nthe majority of Americans because you are allowing junk science and industry influence to \ndetermine your decisions. The CDC has settled too long for data that is poor, inadequate, or no \ndata. It ’s time to modernize, demand rigorous science, embrace transparency , and engage in \nfree and open debate or the entire vaccine program will die. Thank you. \nDavid Wiseman , PhD \nResearch Bioscientist Synechion, Inc. \nThank you very much. Please see our written remarks. FDA has just advised developing \nXBB. 1.5 COVID monovalents. This strategy seems destined to fail with the currently low death \nrate despite the 17% bivalent uptake. Do people agree with Dr. Offit that chasing variants is a \nlosing game? Already 3 months after introduction, the bivalents were alarmingly evaded by XBB \naccording to Wang and other studies omitted from FDA ’s January brief. Cleveland Clinic noted \nthat they were not alone in finding a possible association with more vax doses and higher risk of COVID, and last week, that COVID risk is lower in out -of-date than up- to-date adults. CDC \ninterprets otherwise, but their data echoes ot hers with rapid waning to negative [unclear ] \nsuggesting immune compromise. Rouzine in Nature and FDA ’s brief suggest vaccination \ninfluences evolution and natural selection of escaped variants. Recall Dr. Long’ s comments in \nJanuary 22 that “repeated whack -a-mole boosting was unsustainable. ” Let’s chase safety, not \nvariants. Temporal associations between vax coverage and all -cause mortality persist. Why did \nit take until March for myocarditis to appear in Janssen ’s factsheet and CDC and FDA to report \nthis potential safety concern in the Wu paper? We flagged this signal to ACIP in late 2021. Why \ncan’t they find a stroke signal outside of VSD when it appears in CDC’ s VAERS FOIA release in \nJanuary? That same release shows cancer signals, but still no cancer genot oxic or mutagenicity \nstudies, and yet the National Cancer Institute shows reverse transcription is possible. NIH \nshowed message and spike into the nucleus. Episomal transmission does not need integration. \nFDA’s Dr. Peden writes “DNA can be oncogenic. ” There are reports of possibly replication-\ncompetent residual plasmid template DNA with antibiotic -resistance and undisclosed SV40 \npromoter sequences at levels above guidelines, suggesting adulteration. Excluding these gene \ntherapies from guidance does not change biology or safety concerns. FDA extrapolates further \nthe chasm between EUA “may be effective” and the regular safe and effective standards. The \nbivalents yield novel heterotrimers with untested tox and likely misbranding. Dr. Sanchez ’s \n48 \n \n   \n   \n    \n     \n   \n  \n     \n \n \n   \n \n \n   \n   \n   \n    \n    \n    \n    \n    \n    \n   \n   \n    \n     \n    \n   \n   \n    \n     \n     \n  \n   \n   \n     \n    \n   \n     \n    \n    \n    \n    \n  \n  \n  question last year about spike kinetics remains unanswered, with no FDA insistence for these \nstudies. Lipid nanoparticles widely distribute, spike persists for up to 4 months, mRNA up to 28 \ndays. If you can’ t say where and for how long these gene therapies induce spike production, \nyou shouldn’ t be asking people to vax. Dr. Fauci, in Cell, writes “vaccines have never effectively \ncontrolled these sorts of vaccines, and are not expected to do so. ” Dr. Marks , in JAMA , \nquestions incrementally modifying variant -specific vaccines. Regulate these products as gene \ntherapies, no free passes to poorly understood platforms. Thank you very much. \nMr. Burton Eller \nExecutive Director of Advocacy \nNational Grange \nMy name is Burton Eller. I’m the Executive Director of Advocacy for the National Grange. \nFounded in 1867, the Grange is the oldest national organization advocating for Americans living \nin rural and small -town America. Our mission is to work together to support and advance the \nsafety, health, economic security , and well -being of those who have chosen a rural way of life. \nWe are here today to continue our effort to highlight the vulnerability of our communities to \nrespiratory diseases, and to share our support for ensuring that older Americans most \nvulnerable to RSV have access to the newly FDA -approved vaccines before the start of the \nrespiratory season. As you may know, rural Americans face an elevated risk of serious illnesses \nfrom respiratory diseases. These are due to a number of factors , including the fact that rural \nAmericans are less likely to have health insurance and have less access to healthcare as more and more rural hospitals are closing their doors. A lack of reliable broadband also limits rural Americans ’ ability to access healthcare services. Additionally, rural areas have a higher \npercentage of Americans aged 65 and older versus urban areas. While the COVID -19 \npandemic, in ways, help ed shine light on the positive aspects of living outside of cities, the \nresulting migration of urban residents to rural areas has also put an added strain on our already \nlimited resources. As we saw more adults suffering from RSV last fall and winter, it was almost \nreminiscent of the beginning of the COVID pandemic. News outlets throughout the country were \nonce again reporting the challenges that remaining rural hospitals faced as they tried to cope \nwith the influx of patients needing care , with no space to offer them. Fortunately, with long-\nawaited development and approval of an RSV vaccine, we have the tools to protect ourselves. \nWe thank the committee for your thoughtful consideration of who would be the best served by \nthese vaccines, but we are concerned that these vote for the shared clinical decision- making \nmay create a rather disproportionate impact on rural seniors. Rural providers are stretched thin, \nand their patients tend to be older and sicker. In urban areas, there are 31 physicians for every \n10,000 people, compared to just 13 physicians in rural areas, and there are fewer clinical \nfacilities like clinics and pharmacies. While we believe every American should have the choice \nof whether to receive a vaccine, we also want to ensure equitable access to the information of \nwhat vaccines are available and why they are so important. For rural seniors who do not have easy access to their clinician, any extra step, we fear, could reduce the likelihood that these \npatients will gain access to these protections. Regardless, we are encouraged by those aged 60 \nyears and older who will have the opportunity to consider a protection against RSV, and hope the recommendations are reconsidered in the future as we have more data to indicate whether \nthese most vulnerable communities are truly and adequately being served. Thank you. \n49 \n \n   \n  \n \n     \n   \n    \n \n   \n     \n   \n   \n      \n      \n   \n     \n   \n   \n   \n   \n    \n  \n    \n  \n      \n      \n    \n   \n   \n    \n    \n   \n   \n \n \n \n  \n \n      \n  \n    \n  \n      \n  \n    \n    \n    \n  \n  \n  \n \n      Miss Elizabeth Ditz \nPotential RSV Vaccine Recipient \nMy name is Liz Ditz and I live in San Mateo County, California. Thank you all and to the \ncommittee for the time and expertise that you donate to the nation to improve public health. I ’m \nespecially grateful to Dr. Camille Nelson Kotton this morning for sharing on Twitter the key \nbenefits of the RSV vaccine. I am speaking as a potential RSV vaccine recipient. I’m over 65 \nand have other risk factors for infection with RSV. I am grateful that the committee voted to approve the vaccine, and I’m disappointed that the recommendation is that my age cohort “may” \nget the vaccine with shared decision- making rather than we “should” get the vaccine. Here’s \nwhy. I ’ve been an advocate for vaccines in my community , both in- person and online, for over \n20 years. Until relatively recently, I had no idea that RSV was a significant health risk for people \nover 60. I thought it was only a risk for infants, especially those born prematurely. It ’s hard to \nsell a health intervention like a vaccine if the intended recipient has no idea that the disease prevented is a risk for the recipient. Most people in my age cohort that I know were eager to get \nthe Shingrix vaccine because the suffering caused by shingles is common knowledge. Most \npeople in my age cohort that I know have been vaccinated against pneumococcal disease because of the significant drop in quality of life and hospitalization for pneumonia is common \nknowledge. Most people in my age cohort that I know do take an annual flu vaccine because a \nrisk of flu in our age group is common knowledge. And yes, many in my age cohort do get their \nflu vaccines and others through vaccine clinics or pharmacies. In other words, the vaccine \nrecipient drives the decision to get the vacci ne—not a physician or other healthcare provider. \nWe are in a dangerous era where influential sources are blatantly anti -science. What is the plan \nto explain to older Americans that this is a disease that does not just kill , but significantly impair s \ntheir quality of life? After an ICU stay and hospitalization, it takes a while to return to pre -illness \nbaseline quality of life, independence, and mobility. Because these vaccines will be covered \nunder Medicare Part D and thus administered in pharmacies rather than physicians ’ offices, \nwhat is the plan to educate not just the vaccine- giving pharmacists, but all client -facing \npharmac y staff have to educate elders? I appreciate that the committee voted for “may” rather \nthan “shall” because of a lack of data. What is the plan to collect post -approval data, especially \nin the 80 -and-over age cohort? What ’s the plan for this committee to reconsider this data and to \nchange “may” to “shall? ” Again, thank you all for your hard work, and I hope that this vaccine will \nbe reconsidered soon. \nShinsuke Yamamoto \nMember , Protect Our Future \nHi, thank you. My name is Shin Yamamoto. I ’m a husband, father of 2 kids ages 3 and 9, and a \nmember of the group Protect Our Future, a nonprofit advocating for equitable healthcare and \nCOVID -19 vaccine access for children of all ages. We’ve led a fairly cautious lifestyle since \nMarch 2020 between waiting for vaccinations for all of us and trying to reduce adverse \noutcomes for my wife, who is now on B-cell deplet ion therapy for her relapsing and remitting \nmultiple sclerosis. Considering the problems of autoimmune disease and other chronic illnesses \nin this country, I don’ t think we ’re an isolated case. Many like us have had to make hard choices \nand accept an elevated level of risk that comes with reintegrating into society. I support and welcome the updated COVID- 19 vaccine boosters coming from various manufacturers. I would, \nhowever, like to see simultaneous availability across all ages, which we have not had up to now. \nThis is the most equitable option and one that will ultimately help those of us most at risk who \nstill have to balance our health and the daily lives of our families. Accessibility for pediatric vaccines has been an issue, and I would like to see that addressed as well. Finding a vaccine \nfor your kids should not be as difficult as finding a popular Christmas toy in stock. The same \n50 \n \n    \n  \n \n \n \n \n \n \n   \n  \n   \n    \n      \n \n \n \n \n \n \n  \n \n    \n   \n \n \n \n \n \n \n  \n   \n \n   \n   \n    \n \n \n \n \n \n \n \n  \n \n    \n   thought applies for any vaccination for RSV , which was a cause for so many sick kids in 2022. \nThat is all. Thank you. \nFRIDAY:  JUNE  23, 2023  \nMPOX VACCINES \nBrief Summary \nThe Mpox Vaccines session included a session i ntroduction by Dr. Pablo Sanchez (ACIP, WG \nChair) ; updates from the 2022/2023 US Mpox Outbreak: Epidemiology, Vaccine Safety, and \nVaccine Effectiveness by Dr. Faisal Minhaj (CDC/NCEZID); and presentations on clinical \nguidance for the use of JYNNEOS d uring Mpox outbreaks and c onsiderations for long-t erm \nprotection against Mpox by Dr. Agam Rao (CDC/NCEZID) . No votes were taken on this topic \nduring this meeting. \nMENINGOCOCCAL VACCINES \nBrief Summary \nThe Meningococcal Vaccines Session included a session introduction by Dr. Kathy Poehling \n(ACIP, WG Chair); a presentation on a c ost-effectiveness analysis by Dr. Ismael Ortega-\nSanchez (CDC/NCIRD); and presentations on GRADE/EtR and a summary and WG \nconsiderations by Dr. Sam Crowe (CDC/NCIRD) . No votes were taken on this topic during this \nmeeting. \nVACCINE SAFETY \nBrief Sum mary \nThe Vaccine Safety Session included a presentation of the background on the CDC \nImmunization Safety Office (ISO) and ISO efforts to evaluate studying the safety of the \nchildhood immunization schedule by Dr. Tom Shimabukuro (CDC/NCEZID); a presentation on the childhood immunization schedule and safety from s tudies in the Vaccine Safety Datalink \n(VSD) by Dr. Matthew Daley (Kaiser Permanente Colorado); and a presentation on the \npreliminary evaluation of aluminum content in childhood vaccines and the risk of asthma in a \nDanish nationwide cohort by Dr. Anders Hviid (Sta tens Serum Institut, Copenhagen, Denmark) . \nNo votes were taken on this topic during this meeting. \nCOVID -19 VACCINES \nBrief Summary \nThe COVID -19 Vaccines Session included a session introduction by Dr. Matthew Daley (ACIP \nWG Chair) ; a presentation of updates to COVID- 19 epidemiology and vaccine effectiveness \n(VE) by Dr. Fiona Havers (CDC/NCIRD), Dr. Romeo Galang (CDC/NCCDPHP), and Dr. Ruth \nLink-Gelles  (CDC/NCIRD); a presentation on infection- induced and hybrid immunity by Dr. \n51 \n \n    \n   \n  Jefferson Jones (CDC/NCIRD) ; and a s ummary and presentation of WG considerations by Dr. \nMegan Wallace (CDC/NCIRD. No votes were taken on this topic during this meeting. \n52 \n \n  \n \n \n    \n  \n \n  CERTIFICATION  \nUpon reviewing the foregoing version of the June 21-23 , 2023 ACIP meeting minut es, Dr. Grace \nLee, ACIP Chair, certified that to the best of her knowledge, they are accurate and complete. \nHer original, signed certification is on file with the Management Analysis and Services Office \n(MASO) of CDC. \n53 \n \n  \n  \n \n  \n   \n  \n  \n    \n  \n   \n \n  \n  \n  \n \n \n \n  \n  \n  \n  \n  \n   \n    \n  \n    \n  \n  \n   \n  \n  \n \n  \n    \n   \n  \n  \n  \n   \n  \n  \n   \n   \n    \n  \n  \n \n  ACIP MEMBERSHIP ROSTER  \nCHAIR \nLEE, Grace M, MD, MPH \nAssociate Chief Medical Officer for Practice Innovation Lucile Packard Children’s Hospital \nProfessor of Pediatrics, Stanford University School of Medicine \nStanford, CA \nTerm: 8/4/2021 – 6/30/2023 \nEXECUTIVE SECRETARY \nWHARTON, Melinda, MD, MPH \nNational Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention \nAtlanta, GA \nMEMBERS \nBAHTA, Lynn, RN, MPH, CPH \nImmunization Program Clinical Consultant \nInfectious Disease, Epidemiology, Prevention & Control Division \nMinnesota Department of Health Saint Paul, Minnesota \nTerm: 7/1/2019 – 6/30/2023 \nCHEN, Wilbur H, MD, MS, FACP, FIDSA \nProfessor of Medicine \nCenter for Vaccine Development and Global Health \nUniversity of Maryland School of M edicine \nBaltimore, MD Term: 12/23/2020 – 6/30/2024 \nDALEY, Matthew F, MD Senior Investigator \nInstitute for Health Research, Kaiser Permanente Colorado \nAssociate Professor of Pediatrics University of Colorado School of Medicine \nAurora, CO \nTerm: 1/4/2021 – 6/30/2024 \nKOTTON, Camille Nelson, MD, FIDSA, FAST \nClinical Director, Transplant and Immunocompromised Host Infectious Diseases \nInfectious Diseases Division, Massachusetts General Hospital  \nAssociate Professor of Medicine, Harvard Medical School Boston, MA Term: 12/23/2020 – 6/30/2024 \n54 \n \n  \n  \n \n   \n  \n   \n  \n \n  \n \n \n   \n  \n   \n \n \n \n   \n \n  \n \n \n  \n  \n \n   \n  \n  \n  \n    \n   \n  \n  \n    \n   \n \n   \n  \n  \n \n  \n  LOEHR, Jamie, MD, FAAFP \nOwner, Cayuga Family Medicine Ithaca, New York \nTerm: 7/26/2021 – 6/30/2025 \nLONG, Sarah S, MD \nProfessor of Pediatrics \nDrexel University College of Medicine \nSection of Infectious Diseases \nSt. Christopher’s Hospital for Children \nPhiladelphia, Pennsylvania \nTerm: 12/24/2020 – 6/30/2024 \nMCNALLY, Veronica V, JD \nPresident and CEO Franny \nStrong Foundation \nWest Bloomfield, Michigan Term: 10/31/2018 – 6/30/2022 \nPOEHLING, Katherine A, MD, MPH \nProfessor of Pediatrics and Epidemiology and Prevention Director, Pediatric Population Health Department of Pediatrics \nWake Forest School of Medicine \nWinston- Salem, NC \nTerm: 7/1/2019 – 6/30/2023 \nSÁNCHEZ, Pablo J, MD Professor of Pediatrics \nThe Ohio State University – Nationwide Children’s Hospital \nDivisions  of Neonatal- Perinatal Medicine and Pediatric Infectious Diseases \nDirector, Clinical & Translational Research (Neonatology) Center for Perinatal Research \nThe Research Institute at Nationwide Children's Hospital Columbus, Ohio \nTerm: 7/1/2019 – 6/30/2023 \nTALBOT, Helen Keipp, MD \nAssociate Professor of Medicine Vanderbilt University \nNashville, TN Term: 10/29/2018 – 6/30/2022 \n55 \n \n  \n \n  \n    \n  \n  \n   \n   \n   \n  \n  \n \n   \n \n  \n   \n  \n \n \n  \n  \n \n \n  \n  \n \n  \n \n  \n \n  \n   \n   \n  \n \n  \n  \n   \n \n   \n  \n  \n  EX OFFICIO MEMBERS \nCenters for Medicare and Medicaid Services (CMS)\nHANCE, Mary Beth \nSenior P olicy Advisor \nDivision of Quality, Evaluations and Health Outcomes \nChildren and Adults Health Programs Group \nCenter for Medicaid, CHIP and Survey & Certification Centers \nfor Medicare and Medicaid Services \nBaltimore, MD \nFood and Drug Administration (FDA)\nTBD \nHealth Resources and Services Administration (HRSA)\nGRIMES, Reed, MD, MPH \nCDR, USPHS \nDirector, Division of Injury Compensation Programs \nHealth Systems Bureau \nHealth Resources and Services Administration \nRockville, MD \nIndian Health Service (IHS)\nCLARK, Matthew, MD, FAAP, FACP \nPhysician \nChair, IHS National Pharmacy & Therapeutics Committee Durango, CO \nOffice of Infectious Disease and HIV/AIDS Policy (OIDP)KIM, David, MD, MA Director, Division of Vaccines, OIDP \nOffice of the Assistant Secretary for Health \nDepartment of Health and Human Services \nWashington, DC \nNational Institutes of Health (NIH) \nBEIGEL, John, MD \nAssociate Director for Clinical Research \nDivision of Microbiology and Infectious Diseases National Institute of Allergy and Infectious Diseases (NIAID) \nBethesda, MD \n56 \n \n  \n \n   \n \n   \n  \n  \n  \n  \n   \n  \n  \n \n \n \n  \n \n   \n \n  \n  \n  \n   \n  \n  \n    \n  \n  \n  \n  \n \n  \n   \n  \n  \n \n \n  \n   \n  \n  \n  \n  \n \n  LIAISON REPRESENTATIVES \nAmerican Academy of Family Physicians (AAFP)\nROCKWELL, Pame la G, DO \nAssociate Professor, Department of Family Medicine, University of \nMichigan Medical School \nMedical Director, Dominos Farms Family Medicine \nAnn Arbor, MI \nAmerican Academy of Pediatrics (AAP)\nO’LEARY, Sean, MD, MPH \nProfessor of Pediatrics \nPediatric Infectious Diseases General Academic Pediatrics Children’s Hospital Colorado \nUniversity of Colorado School of Medicine \nAmerican Academy of Pediatrics (AAP) \nRed Book Editor \nKIMBERLIN, David, MD \nProfessor of Pediatrics \nDivision of Pediatric Infectious Diseases The University of Alabama at Birmingham School of Medicine \nBirmingham, AL \nAmerican Academy of Physician Assistants (AAPA)LÉGER, Marie -Michèle, MPH, PA -C \nSenior Director, Clinical an d Health Affairs \nAmerican Academy of Physician Assistants \nAlexandria, VA \nAmerican College Health Association (ACHA)\nCHAI, Thevy S., MD  \nDirector of Medical Services \nCampus Health Services \nUniversity of North Carolina at Chapel Hill Chapel Hill, NC \nAmerican College Health Association (ACHA) (alternate) \nLEE, Sara, MD \nAssistant Vice President of University Health and Counseling Services \nChief Health Officer \nCase Western Reserve University Cleveland, OH \n57 \n \n   \n  \n   \n \n \n   \n  \n   \n    \n \n  \n  \n   \n   \n    \n  \n   \n  \n  \n  \n    \n \n \n  \n \n \n  \n  \n  \n  \n   \n \n  \n  \n  \n \n \n  \n \n   \n \n \n  \n \n  \n  \n \n \n American College of Nurse Midwives (ACNM)\nHAYES, Carol E., CNM, MN, MPH \nLead Clinician \nClinical Quality Compliance and Management Planned Parenthood Southeast  Atlanta, GA \nAmerican College of Nurse Midwives (ACNM) (alternate) \nMEHARRY, Pamela M., PHD, CNM \nMidwifery Educator, Human Resources for Health \nIn partnership with University of Rwanda and University of Illinois, Chicago \nAmerican College of Obstetricians and Gynec ologists (ACOG)\nECKERT, Linda O, MD, FACOG \nProfessor, Department of Obstetrics & Gynecology Adjunct Professor, Department of Global Health \nUniversity of Washington \nSeattle, WA \nAmerican College of Physicians (ACP)\nGOLDMAN, Jason M , MD, FACP \nAffiliate Assistant Professor of Clinical Biomedical Science, Florida Atlantic University, Boca Raton, Florida \nPrivate Practice \nCoral Springs, FL \nAmerican Geriatrics Society (AGS) \nSCHMADER, Kenneth, MD Professor of Medicine- Geriatrics Geriatrics \nDivision Chief Duke University and Durham VA Medical Centers \nDurham, NC \nAmerica’s Health Insurance Plans (AHIP) \nGRUBB, Jessica, MD \nMedical Director, Infectious Diseases \nElevance Health Companies/Carelon Charleston, SC \nAmerican Immunization Registry Association (AIRA) \nCOYLE, Rebecca, MSEd \nExecutive Director, AIRA \nWashington, DC \nAmerican Immunization Registry Association (AIRA) (alternate) \nLONDO, Courtnay, MA Senior Program Manager Washington, DC \n58 \n \n   \n \n   \n  \n  \n  \n  \n   \n  \n  \n  \n  \n  \n  \n \n  \n  \n  \n \n   \n \n   \n \n \n \n   \n  \n    \n \n \n \n   \n  \n \n   \n  \n \n  \n  \n  \n \n  \n \n \n  \n  \n   \n    \n  American Medical Association (AMA)\nFRYHOFER, Sandra Adamson, MD \nAdjunct Associate Professor of Medicine Emory \nUniversity School of Medicine Atlanta, GA \nAmerican Nurses Association (ANA)RITTLE, Charles (Chad), DNP, MPH, RN Assistant Professor, Nursing Faculty \nChatham University, School of Health Sciences \nPittsburgh, PA \nAmerican Osteopathic Association (AOA) \nGROGG, Stanley E, DO Associate Dean/Professor of Pediatrics \nOklahoma State University -Center for Health Sciences \nTulsa, OK \nAmerican Pharmacists Association (APhA)\nGOODE, Jean -Venable “Kelly” R., PharmD, BCPS, FAPhA, FCCP \nProfessor and Director, PGY1 Community -Based Pharmacy Residency Program \nSchool of Pharmacy, Virginia Commonwealth University Richmond, VA \nAssociation of Imm unization Managers (AIM)\nHOWELL, Molly, MPH \nImmunization Program Manager \nNorth Dakota Department of Health \nBismarck, ND \nAssociation for Prevention Teaching and Research (APTR) \nZIMMERMAN, Richard, MD, MPH \nProfessor \nUniversity of Pittsburgh School of Medicine \nDepartment of Family Medicine and Clinical Epidemiology \nPittsburgh, PA \nAssociation of State and Territorial Health Officials (ASTHO)\nJUTHANI, Manisha, MD \nCommissioner \nConnecticut Department of Public Health \nHartford, CT \nBiotechnology Industry Organization (BIO)\nARTHUR, Phyllis A, MBA \nSenior Director, Vaccines, Immunotherapeutics and Diagnostics Policy \nWashington, DC \n59 \n \n    \n  \n  \n \n \n  \n  \n   \n  \n  \n   \n  \n \n \n   \n \n \n \n   \n \n \n \n  \n \n \n \n \n    \n  \n  \n \n  \n  \n  \n  \n  \n  \n  \n     \n   \n \n \n \n   \n  \n  \n  \n  \n  Council of State and Territorial Epidemiologists (CSTE)\nHAHN, Christine, MD \nState Epidemiologist \nOffice of Epidemiology, Food Protection and Immunization Idaho \nDepartment of Health and Welfare \nBoise, ID \nCanadian National Advisory Committee on Immunization (NACI)\nDEEKS, Shelley, MD, MHSc, FRCPC, FAFPHM \nDeputy Chief Medical Officer of Health, Department of Health and Wellness, Nova Scotia Associate Professor, Dalla Lana School of Public Health, University of Toronto \nChair, National Advisory Committee on Immunization \nHalifax, Nova Scotia \nInfectious Diseases Society of America (IDSA)\nDUCHIN, Jeffrey, MD \nHealth Officer, Public Health – Seattle and King County \nProfessor in Medicine, Division of Allergy and Infectious Diseases University of Washington School of Medicine and School of Public Health \nSeattle, WA \nInfectious Diseases Society of America (IDSA) (alternate)\nMCAULEY, James B., DTM&H, MD, MPH \nClinical Director \nWhiteriver Indian Hospital \nWhiteriver, AZ \nInternational Society for Travel Medicine (ISTM)\nBARNETT, Elizabeth D, MD Professor of \nPediatrics \nBoston University School of Medicine \nBoston, MA \nNational Association of County and City Health Officials (NACCHO)\nZAHN, Matthew, MD \nMedical Director, Epidemiology Orange County Health Care Agency \nSanta Ana, CA \nNational Association of County and City Health Officials (NACCHO) (alternate) \nDUCHIN, Jeffrey, MD \nHealth Officer and Chief, Communicable Disease \nEpidemiology and Immuniz ation Section  \nPublic Health - Seattle and King County \nProfessor in Medicine  \nDivision of Allergy and Infectious Diseases University of Washington School of Medicine and School of Public Health \nSeattle, WA \n60 \n \n    \n   \n  \n \n  \n  \n  \n   \n \n \n \n \n \n  \n  \n \n  \n \n  \n  \n  \n  \n   \n  \n \n  \n   \n  \n    \n  \n \n   \n  \n \n \n \n \n  \n    \n   \n \n  \n  \n \n  National Association of Pediatric Nurse Practitioners (NAPNAP)\nSTINCHFIELD, Patricia A, RN, MS, CPNP \nDirector \nInfectious Disease/Immunology/Infection Control \nChildren's Hospitals and Clinics of Minnesota \nSt. Paul, MN \nNational Association of Pediatric Nurse Practitioners (NAPNAP) (alternate) \nDESHON, Dana, DNP, APRN, CPNP -PC \nOrder of Saint Francis Medical Group \nMorton Pediatrics \nMorton, IL \nNational Foundation for Infectious Diseases (NFID)\nSCHAFFNER, William, MD \nChairman, Department of Preventive Medicine \nVanderbilt University School of Medicine Nashville, TN \nNational Foundation for Infectious Diseases (NFID) (alternate) \nDALTON, Marla, PE, CAE \nExecutive Director & CEO \nNational Foundation for Infectious Diseases (NFID) Bethesda, MD \nNational Medical Association (NMA) \nWHITLEY -WILLIAMS, Patricia, MD Professor and Chair \nUniversity of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School \nNew Brunswick, NJ \nPediatric Infectious Diseases Society (PIDS) \nPAULSEN, Grant, MD \nAssociate Professor of Pediatrics \nPediatric Infectious Diseases Cincinnati Children’s Hospital Medical Center Cincinnati, OH \nPediatric Infectious Diseases Society (PIDS) (alternate) \nSAWYER, Mark H, MD \nProfessor of Clinical Pediatric s \nUniversity of California, San Diego School of Medicine San Diego, CA \n61 \n \n  \n  \n \n  \n  \n \n     \n    \n    \n    \n  \n  \n  \n    \n  \n  \n   \n   \n  \n \n \n \n \n  \n  \n  \n \n \n  \n   \n  \n \n  \n  \n    \n \n  Pediatric Infectious Diseases Society (PIDS) (alternate)\nShannon A. Ross, MD, MSPH Professor of Pediatrics \nUniversity of Alabama at Birmingham \nSchool of Medicine Birmingham, AL \nPharmaceutical Research and Manufacturers of America (PhRMA)\nROBERTSON, Corey, MD, MPH \nSenior Director, US Medical, Sanofi Pasteur \nSwiftwater, PA \nSociety for Adolescent Health and Medicine (SAHM)\nMIDDLEMAN, Amy B, MD, MSEd, MPH \nProfessor of Pediatrics Chief, Section of Adolescent Medicine \nUniversity of Oklahoma Health Sciences Center Oklahoma City, OK \nSociety for Healthcare Epidemiology of America (SHEA)MEHROTRA, Preeti, MD, MPH Senior Medical Director \nInfection Control/Hospital Epidemiology \nBeth Israel Deaconess Medical Center Adult and Pediatric Infectious Diseases \nHarvard Medical School Boston, MA \nSociety for Healthcare Epidemiology of America (SHEA) (Alternate)\nDREES, Marci, MD, MS \nChief Infection Prevention Officer & Hospital Epidemiologist ChristianaCare \nWilmington, DE \nAssociate Professor of Medicine \nSidney Kimmel Medical College at Thomas Jefferson University Philadelphia, PA \n62 \n63  \n  \n  \n   \n  \n   \n   \n  \n  \n   \n   \n    \n     \n  \n   \n  \n   \n   \n  \n   \n   \n   \n   \n   \n   \n    \n  \n  \n   \n  \n    \n   \n   \n  \n  \n    \n  \n  \n  \n  \n   \n   \n    \n  \n   \n    \n   \n  ACRONYMS USED IN  THIS  DOCUMENT   \nAAFP American Academy of Family Physicians \nAAP American Academy of Pediatrics \nABCs Active Bacterial Core Surveillance System \nACA Affordable Care Act \nACHA American College Health Association \nACIP Advisory Committee on Immunization Practices \nACOG American College of Obstetricians and Gynecologists \nACP American College of Physicians \nADE Antibody -Dependent Enhancement \nADHD Attention Deficit Hyperactivity Disorder \nAE Adverse Event \nAESI Adverse Event of Special Interest \nAHIP America’s Health Insurance Plans \nAI/AN American Indian/Alaskan Native \nAIDP Acute Inflammatory Demyelinating Polyneuropathy \naIIV Adjuvanted Influenza Vaccine \nAIM Association of Immunization Managers \nAIRA American Immunization Registry Association \nAMA American Medical Association \nAMETHST American Transformative HIV Study \nAMIS American Men’s Internet Survey \nAOA American Osteopathic Association \nAOM Acute Otitis Media \nAPhA American Pharmacists Association \nAR Adverse Reaction \nARI Acute Respiratory Illness \nASPR Administration for Strategic Preparedness and Response \nASTHO Association of State and Territorial Health Officers \nAUC Area Under the Curve \nBARDA Biomedical Advanced Research and Development Authority \nBEST System Biologics Effectiveness and Safety System \nBLA Biologics License Application \nCBER Center for Biologics Evaluation and Research \nCBO Community -Based Organization \nccIIV4 Cell-Culture Based Vaccine \nCDC Centers for Disease Control and Prevention \nCHD Chronic Heart Disease \nCHIKV Chikungunya Virus \nCHIP Children’s Health Insurance Program \nCICP Countermeasures Injury Compensation Program \nCISA Clinical Immunization Safety Assessment Project \nCLD Chronic Lung Disease \nCLI COVID -Like Illness \nCMC Chronic Medical Conditions \nCMS Center for Medicare and Medicaid Services \n \n    \n   \n   \n  \n   \n  \n   \n   \n  \n   \n   \n  \n   \n  \n  \n   \n   \n    \n  \n  \n    \n  \n   \n  \n  \n  \n  \n   \n  \n  \n   \n   \n   \n   \n   \n   \n   \n   \n  \n   \n  \n  \n  \n  \n   \n   \n   \n   \n    CMV Cytomegalovirus \nCOI Conflict of Interest \nCONUS Continental United States \nCOPD Chronic Obstructive Pulmonary Disease \nCOVID -NET Coronavirus Disease 2019 (COVID -19) Hospitalization Surveillance Network \nCSF Cerebrospinal Fluid \nCSTE Council of State and Territorial Epidemiologists \nCVD Cardiovascular Disease \ncVDPV2 Circulating Vaccine -Derived Poliovirus Type 2 \nDCAC Dengue Case Adjudication Committee \nDENV Dengue Virus \nDFO Designated Federal Official \nDM diabetes mellitus \nDoD Department of Defense \nDSMB Data Safety Monitoring Board \nDUA Data Use Agreement \nDVA Department of Veterans Affairs \neCRF Electronic Case Report Form \nED Emergency Department \nEIND Emergency Investigational New Drug \nEMA European Medicines Agency \nEMDS Enhanced Meningococcal Disease Surveillance \nEMR Electronic Medical Record \nET Eastern Time \nEtR Evidence to Recommendation \nEU European Union \nEUA Emergency Use Authorization \nFAERS FDA Adverse Event Reporting System \nFAS Freely Associated States \nFDA Food and Drug Administration \nFluSurv -NET Influenza Hospitalization Surveillance Network \nFQHC Federally Qualified Health Centers \nFRN Federal Register Notice \nFRPP Federal Retail Pharmacy Program \nGACVS Global Advisory Committee on Vaccine Safety \nGBS Guillain -Barré Syndrome \nGDP Gross \n…[truncated]", "summary": "MEETING OF THE ADVISORY  COMMITTEE ON IMMUNIZATION  PRACTICES (ACIP)  JUNE 21 -23, 2023  MEETING SUMMARY  CONTENTS   WEDNESDAY: JUNE 21, 2023 .................................................................................................................... 3  WELCOME AND INTRODUCTIONS ...................................................................................... 3  Call to Order/Roll Call…", "source_url": "https://www.cdc.gov/acip/meetings/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/minutes/summary-2023-06-21-23-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "minutes", "tags": ["acip", "cdc", "vaccines", "minutes"], "page_count": 67}
{"title": "agenda 2023 04 19 508.pdf", "content": "Final - April 18, 2023 \nMEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP) \nCenters for Disease Control and Prevention \nAtlanta, Georgia 30329  \nApril 19, 2023 \nAGENDA ITEM \nWednesday, April 19, 2023 PRESIDER/PRESENTER(s) \n11:00 Welcome & Introductions Dr. Grace Lee (ACIP Chair) \nDr. Melinda Wharton (ACIP Executive Secretary, CDC) \n11:10 Coronavirus Disease 2019 (COVID-19) Vaccines \nIntroduction COVID-19 vaccine program updates COVID-19 vaccine safety updates \nUpdate: v-safe after vaccination health checker COVID-19 vaccine effectiveness updates  \nUpdates to COVID-19 vaccine policy: data and work  \ngroup considerations \nClinical considerations updates Dr. Matthew Daley (ACIP, WG Chair) \nDr. Georgina Peacock (CDC/NCIRD) Dr. Tom Shimabukuro (CDC/NCEZID) \nDr. Tom Shimabukuro (CDC/NCEZID) Dr. Ruth Link-Gelles (CDC/NCIRD) \nDr. Sara Oliver (CDC/NCIRD) \nDr. Evelyn Twentyman (CDC/NCIRD) \n1:15 Break \n1:30 Public Comment \n1:50 Committee discussion \n3:00 Adjourn \nAcronyms \nCDC Centers for Disease Control and Prevention \nCMS Centers for Medicare and Medicaid Services \nCOVID-19 Coronavirus disease 2019 \nEtR Evidence to Recommendations Framework \nFDA Food and Drug Administration \nGRADE Grading of Recommendations Assessment, Development and Evaluation \nHRSA Health Resources and Services Administration \nIHS Indian Health Service \nNCHHSTP National Center for HIV, Hepatitis, STD and TB Prevention [of CDC/DDID] \nNCIRD National Center for Immunization & Respiratory Diseases [of CDC/DDID] \nNCEZID National Center for Emerging and Zoonotic Diseases [of CDC/DDID] \nNIAID National Institute of Allergy and Infectious Diseases \nOIDP Office of Infectious Disease and HIV/AIDS Policy \nSARS-CoV-2 Severe Acute Respiratory Syndrome Coronavirus 2 \nWG Work Group \nWHO World Health Organization \nVaST COVID-19 Vaccine Safety Technical (VaST) Work Group \nVE Vaccine Effectiveness", "summary": "Final - April 18, 2023  MEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)  Centers for Disease Control and Prevention  Atlanta, Georgia 30329   April 19, 2023  AGENDA ITEM  Wednesday, April 19, 2023 PRESIDER/PRESENTER(s)  11:00 Welcome & Introductions Dr. Grace Lee (ACIP Chair)  Dr. Melinda Wharton (ACIP Executive Secretary, CDC)  11:10 Coronavirus Disease 2019 (COVID-19) Vaccines  Introduction COVID-19 vaccine program updates COVID-19 vaccine safety updates  Update: v-safe…", "source_url": "https://www.cdc.gov/acip/meetings/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/agendas/agenda-2023-04-19-508.pdf.pdf", "doc_date": "2023-04-19", "case": "acip", "sub_case": "agendas", "tags": ["acip", "cdc", "vaccines", "agendas"], "page_count": 1}
{"title": "summary 2023 04 19 508", "content": "MEETING OF THE ADVISORY \nCOMMITTEE ON IMMUNIZATION \nPRACTICES (ACIP)  \n \nAPRIL 19 , 2023 \nMEETING SUMMARY  \n \nCONTENTS  \nWEDNESDAY: APRIL 19, 2023 .................................................................................................................... 2  \nWELCOME AND INTRODUCTIONS  ...................................................................................... 2  \nCall to Order/Roll Call ......................................................................................................... 2  \nAnnouncements  .................................................................................................................. 2  \nCOVID -19 VACCINES  ............................................................................................................ 4  \nSession Introduction ........................................................................................................... 4  \nCOVID -19 Vaccine Program Updates  ................................................................................. 4  \nmRNA COVID -19 Bivalent Booster Vaccine Safety Update  ................................................ 7  \nv-safesm After Vaccination Health Checker  .........................................................................12 \nCOVID -19 Vaccine Effectiveness Updates  .........................................................................14 \nUpdates to COVID -19 Vaccine Policy: Considerations for Future Planning ........................19 \nUpdates to Interim Clinical Considerations for Use of COVID -19 Vaccines  ........................23 \nPUBLIC COMMENT  ..............................................................................................................29 \nOverview  ............................................................................................................................29 \nPublic Comments  ...............................................................................................................29 \nCERTIFICATION  ......................................................................................................................................... 33 \nACIP MEMBERSHIP ROSTER  .................................................................................................................. 34 \nACRONYMS USED IN THIS DOCUMENT  ................................................................................................. 42 \n \n  \n2 \n  \nWEDNESDAY : APRIL 19, 2023  \n \nWELCOME AND I NTRODUCTIONS  \n \nCall to Order/Roll Call  \n \nDr. Grace Lee (ACIP Chair) called to order and presided over the April 19, 2023 Advisory \nCommittee on Immunization Practices  (ACIP ) meeting.  Dr. Lee co nducted a roll call, which \nestablished that a quorum was present.  A list of Members, Ex Officios , and Liaison \nRepresentatives is included in the appendixes at the end of this summary document.  No \nconflict s of interest (COIs) were  identified.  The following potential COI was identified: \n \n\n Dr. Camile Kotton is involved in a clinical trial for Takeda for an investigational antiviral that does not involve any work with vaccines.  \n \nAnnouncements  \n \nDr. Melinda Wharton (ACIP Executive Secretary, CDC)  noted  that copies of the slides for the \nmeeting were available on the ACIP website and were made available through a ShareLink ™ \nfile for voting ACIP Voting, E x Officios , and Liaisons  Members . The ACIP  is, at its heart, a public \nbody. Engagement with the public and transparency in all of its processes are vital to the committee’s work. She indicated that there would be 1 oral public comment session during this \nmeeting, which was scheduled for 1:30 PM Eastern Time ( ET). To create a fair and more \nefficient process, individuals interested in making an oral comment were asked to submit a request online in advance of the meeting. Priority is given to these advance requests.  If more \npeople make requests than can be accommodated, a blind lottery is conducted to determine who the speakers will be. Speakers selected in the lottery for this meeting were notified in advance of the meeting. Members of the public also may submit written comments via \nhttps://www.regulations.gov  us\ning Docket Number  ID CDC- 2023-0 028. Information on the \nwritten public comment process, including information on how to make a comment,  can be \nfound on the ACIP website.  \n \nA\ns noted in the ACIP Policies and Procedures manual, ACIP members agree to forgo \nparticipation in certain activities related to vaccines during their tenure on the committee. For certain other interests that potentially enhance a member’s expertise  while serving on the \ncommittee , CDC may issue limited COI waivers. Members who conduct vaccine clinical trials or \nserve on  data safety monitoring board s (DSMB s) may present to the committee on matters \nrelated to those vaccines, but those m embers are prohibited from participating in committee \nvotes  on issues related to those vaccines. Regarding other vaccines of the concerned company, \na member may participate in discussions with the provision that he/she abstains on all votes \nrelated to that  company. ACIP members state  any COIs  at the beginning of each meeting.  \n Dr. Wharton reported that Since the COVID -19 vaccination program began in the United States  \n(US) in December, 2020,  more than 670 million doses of COVID- 19 vaccines have been \nadministered  to 270 million people. A lot has happened since the original authorizations of \nCOVID -19 vaccines.  There have  been multiple changes to recommendations for vaccine use as \nadditional vaccines became available and vaccines were authorized for additional age groups.  \nDuring the February 2023 ACIP meeting,  there was discussion of future directions for the \nCOVID -19 vaccination program.  This proposal included moving toward a single dose of an  \n3 \n updated vaccine for most people,  and additional doses needed  only for young children who may \nnot yet have been exposed to COVID , older  adults, and immunocompromised people. With  the \nprevious day’s regulatory action by the Food and Drug Administration  (FDA) , a large step was \ntaken in this direction. She invited colle agues from the FDA to provide an update on  that action.  \n \nPeter Marks M., PhD (CBER/FDA)  indicated that FDA’s ultimate objective is to improve public  \nhealth by facilitating better updated COVID -19 vaccine coverage  and those eligible for \nvaccination. The previous day’s action was an initial effort , based  on the totality of evidence  \navailable,  to simplify the vaccination regimen for most individuals  and authorize the current \nbivalent vaccines to be used for all doses administered to individuals 6 months of age  and older, \nincluding an additional dose or doses for certain populations.  Most  individuals, depending on \nage previously vaccinated with an original or monovalent COVID -19 vaccine,  who have not  \nyet received the do se of a bivalent vaccine, may receive a single dose of a bivalent vaccine.  \nMost unvaccinated individuals may receive a single dose of a bivalent vaccine rather than  \nmultiple doses  of the original monovalent mRNA vaccines in order to be considered protected.  \nMost individuals who have already received a single dose of the bivalent vaccine are not \ncurrently eligible  for another dose with some exceptions. The FDA intends to make decisions  \nabout future vaccination for all of the various populations after receiving recommendations on \nthe strain composition at an FDA Vaccines and Related Biological Products Advisory Committee \n(VRBPAC) m eeting to be held in June  2023,  at which time strain selection will be discussed \nfor the coming year or season.  As noted, individuals 65 years of age  and older who have  \nreceived a single dose of a bivalent vaccine may receive one additional dose of vaccine at least \n4 months following their initial bivalent dose. M ost individuals with certain kinds  of \nimmunocompromise who have received a bivalent COVID -19 vaccine may receive a single \nadditional dose of a bivalent COVID -19 vaccine at least 2 m onths following a dose of that  \nvaccine.  Additional doses may be administered at the discretion of and intervals determined by \ntheir healthc are provider  (HCP). The one exception is for immunocompromised individuals 6 \nmonths through 4  years of age  for whom the eligibility  for additional doses will depend upon the \nvaccine previously given to the individual.  Children 6 months through 5 years of a ge who are \nunvaccinated may receive a 2 -dose series of the Moderna bivalent vaccine.  Children 6 months \nthrough 4 years of age may receive a 3 -dose series  of the Pfizer -BioNTech bivalent vaccine.  \nChildren 5 years of age may receive either 2  doses  of the Moderna bivalent vaccine or a single \ndose of the Pfizer -BioNTech bivalent vaccine.  Children 6 months through 5 years of age who \nhave received 1 , 2, or 3 doses  of a monovalent COVID -19 vaccine may receive a bivalent  \nvaccine, which is essentially to complete  that initial vaccination series. FDA realize s that this \nupdated regimen is still  somewhat more complicated than desirable but view s it as an interim \nstep moving into the next cycle of strain selection, which is coming up in late Spring to early \nSummer.  FDA will f urther consolidate and simplify the regimen as  labeling is further updated  for \nthese vaccines.  Ultimately, the goal is to have the regimen simple enough for patients to easily \nunderstand  and providers to easily administer. For now, the key message is that for older  \nchildren and adults up to age 65,  a single bivalent vaccine is appropriate for prevention of \nCOVID -19 under the current Emergency Use Authorization (EUA) . In terms of those who have \nreceived non -mRNA vaccines, FDA will be discussing with manufacturers how to further update \nthose vaccines  so that there will be options available moving forward. The previous day’s action \ndoes not affect those vaccines at this time.  \n \nDr. Grace Lee (ACIP Chair)  thanked FDA colleagues for their continued attention to addressing \nthe COVID -19 pandemic, recognized that this is an evolution of recommendations or \nauthorizations over time, and expressed appreciation for FDA’s attempt to a more simplified \nfuture state.  \n  \n4 \n  \nCOVID -19 VACCINES  \n \nSession Introduction  \n \nDr. Matthew F. Daley (ACIP WG Chair)  introduced this session on behalf  of the ACIP COVID -\n19 Vaccines Work Group  (WG) . As they just heard from Dr. Marks,  there were FDA  \nauthorizations on April 18, 2023  that includ ed updating the COVID -19 Vaccine EU A, including \nthe use of bivalent mRNA vaccines  for all doses and indications administered to individuals \nages 6 months and older  and additional doses for certain specific populations.1 \n Since the February 2023 ACIP meeti ng, the COVID -19 Vaccines WG  reviewed a number of \ndata points around pediatric COVID -19 vaccination.  They also reviewed the epidemiology of \nCOVID -19, including among adults ≥65 years of age. The WG heard a number of vaccine \neffectiveness  (VE) updates . In a ddition, they reviewed preliminary results  from pediatric cost -\neffectiveness analyses  and discussed additional doses in vulnerable populations.  The February \n24, 2023 ACIP meeting  included COVID -19 updates and discussions on vaccine safety , VE, \nand epidemiology and hospitalization data. In addition, there were presentations and discussions on a benefit -risk analysis, c onsiderations for transition to a bivalent primary series , \nand future directions of COVID -19 vaccines, including updates to vaccine policy . \n \nThe session on April 19 included vaccine safety updates , VE data updates, presentations on \nepidemiology and hospitalization data and a benefit -risk analysis, c onsiderations for transition to \nbivalent primary series , and discussion on f uture directions of COVID -19 vaccines —including \nupdates to vaccine policy . \n \nCOVID -19 Vaccine Program Updates  \n \nGeorgina Peacock, MD, MPH, FAAP (CDC/NCIRD) presented COVID -19 Vaccine Program \nupdates. As  a reminder, she reviewed the key objectives that were set forward at the beginning \nof the pandemic , which were to: 1) ensure safety  and effectiveness ; 2) reduce mortality, \nmorbidity,  and the incidence of COVID -19 disease; 3) h elp minimize disruption to society and \nthe economy,  including maintaining healthcare capacity; and 4) ensur e equity in vaccine \nallocation and distribution.  \nMoving into the next phase, it is important to keep these objectives in mind  for the US COVID -\n19 Vaccination Program . In terms of the reasons for changes in the program, the Public Health \nEmergency (PHE) will end on May 11, 2023. Regarding what will change, it is possible that there will be reduced submission of vaccine administration data from some jurisdictions  on a \nnational level . This is going to limit the completeness  of the administration data that can be \nreported report on a national level. CDC has  been working with jurisdictions  to sign an extension \nof their COVID -19 Data Use Agreement s (DUAs)  that will extend CDC’s ability to get data f rom \nmost states until the end of 2023. It is expected  that that a few jurisdictions  may not submit \nthose data based on state laws and other issues that are impacted by the end of the PHE . \nNevertheless, CDC still will be getting the majority of administration data on COVID -19 \nvaccines. Other things will not change. CDC will continue to work  with public and private \npartners to learn more about the short - and long- term health effects associated with COVID -19 \nin terms of who is affecte d and why and to implement vaccine recommendations  to optimize  \n \n1 https://www.fda.gov/news- events/press -announcements/coronavirus- covid -19-update- fda-authorizes -changes -simplify -use-\nbivalent -mrna -covid -19-vaccines   \n5 \n protection. FDA’s EUAs will remain in place for COVID -19 products, including vaccines,  even \nbeyond the PHE . All vaccines purchased by the US Government  (USG) will continue to be \ndistributed and available for free. CDC is committed to ensuring a strong immunization program \ngoing forward as changes continue to occur.  \n Commercialization  of COVID -19 vaccines is expect ed to occur in early Fall 2023. \nCommercia lization is the transition of vaccines  previously purchased by the US G to established \npathways  of procurement, distribution,  and payment for vaccinations  by public and private \npayers.\n2 Considerations include what will be authorized by FDA and recommended by CDC, \nand the alignment with any  strain changes due to potential variants. After commercialization , \nvaccines will remain free for most people through the Vaccines for Children Program  (VFC), the \nChildren ’s Health Insurance Program  (CHIP) , most commercial  insurance, and Medicare  and \nMedicaid programs . \n \nA focus on vaccination equity has been a very important part of the COVID -19 Program.  CDC \nhas been working with national, state, tribal, and territorial health departments; healthcare; and \ncommunity partners to ensure that all people have fair  and just access to vaccination. This  effort \nalso has addressed many issues related  to vaccine confidence. Given that access and \nconfidence go hand- in-hand, there has been a major emphasis on these over the past couple of \nyears. CDC uses a S ocial Vulnerability Index  (SVI)3 to support areas that are at increased risk. \nThe SVI allows health departments  and others to look at  vaccine coverage at  the sub -county  \nand C ensus track levels to determine where there is  social vulnerability  in order to target efforts \nto increase vaccine coverage. Making sure that uninsured adults have continued access to \nCOVID -19 vaccines with as few financial barriers as possible is a top priority.  \n An important announcement was made by the HHS Secretary  in the last few days that t here will \nbe an “HHS Bridge Access Program For COVID -19 Vaccines and Treatments ” for uninsured \nadults.\n4 This program is being put in place  to serve th e 30 million uninsured adults in the US. \nThis supports the existing public sector vaccine safety net.  Traditionally, CDC has  worked with  \nstate  and local health department partners to make vaccines available through the 317 Program \nthat provides vaccines and supportive infrastructure to vaccinate uninsured adults.  Funding for \nthis effort will be made available through this existing program.  Funding  also will be going to \nFederally Qualified Health Centers  (FQHCs) . In addition, there will be a funded partnership with \npharmacy chains. This will allow another way for uninsured adults  to be able to receive vaccines \nfree of charge.  A major development  over the last couple years and throughout the pandemic is  \nthat pharmacies have been a key partner in helping to increase access to COVID vaccine. \nPharmacy partners  administered COVID vaccine during the pandemic, which is an important \nmodel in terms of consideration of the domestic vaccine program.  CDC is committed  to thinking \nthrough and supporting pharmacy networks in terms of moving forwa rd in this new phase of the \nCOVID vaccine program.  One of the ways to do this is through the Bridge Program for the \nuninsured.  \n  \n \n2 https://aspr.hhs.gov/COVID -19/Pages/FAQ -Commercialization.aspx   \n3 https://www.atsdr.cdc.gov/placeandhealth/svi/at -a-glance_svi.html   \n4 https://www.hhs.g ov/about/news/2023/04/18/fact -sheet -hhs-announces -hhs-bridge- access -program -covid -19-vaccines -treatments -\nmaintain- access -covid -19-care-uninsured.html   \n6 \n Another issue that has arisen that affects the COVID -19 Vaccine Program is the  Public \nReadiness and Emergency Preparedness  Act (PREP Act ) for Medical Countermeasures against \nCOVID -19.5 HHS  recently announced an intention to amend the declaration under the PREP \nAct for Medical Countermeasures against COVID -19. By issuing this amendment,  the HHS \nSecretary intends to extend immunity  liability to pharmacists, pharmacy interns, and pharmacy \ntechnicians to administer COVID -19 and seasonal influenza vaccines through December 2024.  \nThis amendment will allow for the ability of pharmacists to vaccinate children for routine \nvaccinations down to 3 years of  age. \n Another important development is the Inflation Reduction Act,\n6 which includes some key  \nprovisions that eliminated cost -sharing for all ACIP -recommended vaccinations under Medicaid \nand Medicare Part D or equivalent plans.  This started on January 1, 2023 and is  continuing to \nbe implemented. While not yet fully in place, it guarantees  that nearly 50 million Medicare \nbeneficiaries and more than 80 million Medicaid beneficiaries will have access  to all ACIP -\nrecommended vaccinations for adul ts without any cost -sharing.  This is a very important  \ndevelopment for the coverage of vaccines across the lifespan.  \n \nDespite these advances, a comprehensive Vaccines for Adult s (VFA) Program  is still needed \nthat will fill in th e gaps in places  where no coverage  is currently available.  The proposed VFA \nwould reduce the spread of vaccine- preventable diseases and pave the way for greater health \nequity. In CDC’s FY24 President’s Budget Request, there is a request for the proposed VFA \nProgram. This $1.2 billi on request  for FY24 equates  to $12 billion over 10 years  that would be \nutilized for vaccine purchase, program operations , provider administration, and provider fee  \nreimbursement . This would cover all ACIP -recommended vaccines  for uninsured adults, which \nequates to approximately 30 million people in the US . In addition to this, not included in the VFA \nproposal,  is the important provision for the support  of vaccine confidence and equity activities \nneed to continue  through the discretionary funding related to Section 317. \n \nDiscussion Points  \n Dr. Duchin (IDSA) expressed concern about cessation of reporting of vaccine administration \ndata, given that it seems critical to ensuring equity in access and distribution.  He requested \ninformation about how this gap would be addressed long- term and whether it is part of the new \ninformatics initiative the CDC is working on. He applauded the movement forward in terms of \nthe Adult Vaccination Program  after so many years of adv ocacy by the National Vaccine \nAdvisory Committee (NVAC) and others  and asked what specifically  would be provided to state  \nand local health departments that administer these vaccines and carry out many of the  \nrelationships  with community providers.  \n Dr. Pea cock emphasized that there  has not been complete cessation of reporting of  \nadministration data.  There will be some decreases after this PHE, most of which is related to \nstate laws  that prohibit sharing these  data with the federal  government.  CDC is working  with its \nstate partners to determine whether there are ways to continue to receive vaccine \nadministration data related to COVID and routine vaccinations.  Putting an extension of the \nDUAs  into place for COVID  and negotiation of r outine vaccination DU As should be helpful. For \nCOVID vaccine s, the CDC COVID- 19 Vaccination Program Provider Agreement  is still in place . \nAt the peak, over 120,000 providers  were providing COVID vaccine . The agreement includes a \nprovision that providers need to report administration data of COVID vaccine. While it is \n \n5 https://www.hhs.gov/about/news/2023/04/14/factsheet -hhs-announces -amend- declaration- prep- act-medical -countermeasures -\nagainst -covid19.html   \n6 https://www.cms.gov/newsroom/fact -sheets/inflation- reduction- act-lowers -health- care-costs -millions -americans   \n7 \n probable that CDC will not have the full  picture of what is occurring nationally , state health \ndepartments will still have these data within  their Immunization Information Systems (IISs) . It will \nstill be necessary to consider ways  to ensur e equity  moving forward . There will be challenges, \nbut CDC has supported many partners who have been working with community -based \norganizations  (CBOs)  to examine access and  confidence issues.  This work is continuing to be \nfunded and move forward.  In relation to the Adult Program and support of state  and local health \ndepartments, that work is critical. As a domestic program is implemented that serves people \nacross the lifespan, the infrastructure that has been built  to serve children over the last 30 years \nthrough the VFC Program serves as  a basis for providing vaccines for adults  through a VFA  \nProgram. Built into that is an increase in the infrastructure, which is essentially the jurisdiction  \nawardee that CDC funds . That is an important part of the VFA proposal.  \n \nDr. Sanchez  requested clarification with  regard to  the amendment to the PREP Act  in terms of \nchildren down to 3 years of age and how that applies  to vaccine provided to children and  \npregnant women . \n Dr. Peacock clarified that the PREP Act allowed for a number of vaccinators  to vaccinate people \nall down to 3 years of age . Typically, there are state laws that differ by state that designate  who \ncan be vaccinators.  The PREP Act extended the ability to vac cinate to pharmacists, pharmacy \ntechs, and  pharmacy interns for COVID- 19 vaccine,  influenza vaccine, and routine childhood \nvaccination.  This has been ongoing throughout the pandemic.  The amendment to the PREP Act  \nallows certain provisions to continue. Cert ain provisions  allow influenza and COVID vaccination  \nto continue down to 3 years of age, so there is coverage across the nation for that.  That \nprovision was not extended for routine childhood immunization, which now revert back to state laws. She apologized for not having any details on pregnant women.  \n Dr. Dale y expressed gratitude for the continuing advocacy for the VFA Program.  Although death \nfrom COVID -19 is largely vaccine- preventable,  it seems completely unfair that the ability to \naccess that vaccine is related to whether someone has health  insurance. \n \nDr. Peacock stressed that the announcement of the B ridge Program  represented an important  \nstep forward toward ensuring administrative of a vaccination program  that serves people across \nthe lifespan.  \n \nmRNA COVID -19 Bivalent Booster Vaccine Safety Update  \n \nTom T. Shimabukuro, MD, MPH, MBA (CDC/NCEZID)  described current data on ischemic \nstroke following mRNA COVID- 19 bivalent booster vaccination from the following systems: \n  CDC’s Vaccine Safety Datalink (VSD) Rapid Cycle Analysis (RCA) signal assessment for \nischemic stroke after Pfizer -BioNTech COVID -19 mRNA bivalent booster dose vaccination \nin the age group ≥65 years old  \n \n Vaccine Adverse Event Reporting System (VAERS) data on ischemic stroke following \nmRNA COVID -19 bivalent booster dose vaccination \n \nAs a reminder, the VSD is CDC’s  active , electronic health record (EHR) -based surveillance \nsystem that was established in 1990 as a collaborative project between CDC and 9 integrated \nhealthcare organizations. These analyses included the 9 participating sites  that have data on a \ntotal of about 12.5 million individuals.  \n  \n8 \n VSD RCA pre -specified outcomes were assessed during weekly sequential monitoring after  \nbivalent booster vaccination.  The risk of pre- specified outcomes in 1 to 21 days following \nvaccination were compared with bivalent vaccinated individuals who were 22 to 42 days out  \nfollowing the bivalent dose.  This is a vaccinated concurrent comparator method  that assesses \ncases in vaccinated individuals  in the risk window of 1 to 21 days compared to cases in \nvaccinated individuals  in the comparison interval at  22 to 42 days. All analyses were  adjusted \nfor age, sex, race and ethnicity,  VSD site , calendar time (days) , and seasonality  (time).  The \nsignaling threshold is a 1 -sided p-value <0.01 . \n \nThis table shows the pre -specified outcomes  that were  monitored in the COVID -19 Vaccine \nRCA and the settings in which they were monitored:  \n \n \n \nIn the COVID -19 booster vaccination monitoring,  the RCA detected a statistical signal for \nischemic stroke  after Pfizer -BioNTech bivalent booster vaccination in the age group 65 years \nand older.  No other VSD RCA pre -specified surveillance outcomes have signaled in any age \ngroup for either of the mRNA COVID -19 bivalent boosters or when data for the 2 mRNA  vaccine \ntypes were combined or pooled.  VSD investigations  of an RC A signal to assess  whether it \nreflects a real effect of vaccination on an outcome include several steps,  including the following:  \n \n Data quality assessment for errors, anomalies, or missing or late- arriving data  \n Analyses using different comparators than the primary concurrence  (e.g., un-boosted,  \nunvaccinated, or “ historical ” comparators ) to supplement the primary analyses  \n Additional investigations to provide context , such as background rates  \n Graphic displays of outcome incidents, day -by-day after vaccination , using temporal scan \nstatistics  to assess apparent clustering to examine the temporal clustering of outcome \nevents in subgroups defined by demographics, site, or simultaneous exposure (e.g., influenza vaccine)  \n Further analyses by site or subgroup conducted as appropriate if the signal is driven by a \nstrong association  in one subgroup or VSD site  \n Chart review to confirm cases and collect additional data,  such as date of s ymptom onset  \n Consideration of epidemiologic studies to further investigate surveillance findings  \n  \n\n9 \n Moving now to the results of the VSD COVID -19 RCA analyses of ischemic stroke after Pfizer -\nBioNTech bivalent booster among people ≥65 years of age,  substantially more Pfizer -BioNTech \n(643,372)  booster vaccines were administered during the bivalent booster program compared to \nModerna  (355,767) between 8/28/22 and 4/8/23. There were substantially more doses \nadministered early in the booster program, with the peak of COVID -19 bivalent booster with  \nPfizer -BioNTech at about the same time as  peak influenza vaccination in this age group.  \n \nThis table reflects the VSD RCA ischemic stroke case definition, onset date, codes to detect \nprevalence, and exclusion criteria:  \n \n \n In terms of the  bivalent RCA concurrent comparator  analysis o f ischemic strokes during a 1-  to \n21-day risk interval versus a 22 - to 24-day comparison interval , the primary analysis  was the \nvaccinated concurrent comparator , shown for the most current weekly analysis  with d ata \nthrough April 8, 2023.  This analysis was broken down by age groups 18─ 64 years and 65+ \nyears . While younger age groups were assessed, ischemic stroke is a very rare outcome  and \nthose data are not informative for this analysis. For the most recent sequential analysis by the 2 \nage groups and by vac cine (Pfizer, Moderna)  none of the  findings met the signaling threshold,  \nwhich is a p -value of <0.01. In the nominal analysis,  all the 95% confidence intervals included \n1.0, so it also was not statistically significant. As Dr. Shimabukuro recalled, the last time he \nshowed these data, the nominal analysis for Pfizer vaccine among persons ≥65  years of age the  \nwas statistically significant  and the sequential analysis did not hit the signaling threshold.  \n In the weekly analys es ischemic stroke after Pfizer -BioNTech bivalent booster  for persons  age \n≥65 years  from October 16, 2022  through April 8, 2023, the rate ratio  was 1.26 with a 95% \nconfidence interval of 0.99 to 1.60  as of April 2, 2023.  A statistical signal for ischemic s troke  \nfollowing the Pfizer -BioNTech bivalent booster  in this age group was first detected in November  \n2022.  This signal persisted through January 2023 , but did not meet the signaling threshold for \nthe last 10 weekly analyses.  An important caveat is that in  the VSD RCA, once there is a signal, \nthere always is a signal.  While the most recent 10 weekly analys es did not meet the statistical  \nthreshold for a signal, there still was a signal  for this outcome. However, CDC continues to \nfollow these weekly analyses over time because  they think it is informative  to do so.  \n  \n\n10 \n In addition to the primary analysis,  supplemental analyses  also are performed. The \nsupplemental RCA analyses  assessing ischemic strokes in the 1 - to 21 -day risk interval \ncomparing bivalent boosted to unboosted concurrent comparators  can be thought of as a \nvaccinated versus unvaccinated comparison . A note for this particular analysis  is that it is not \ntruly a vaccinated versus unvaccinated : it is a bivalent booste d versus unboosted, but eligible \nfor a booster.  These individuals probably  are more similar than true vaccinated versus  \nunvaccinated.  In the supplemental analyses, the adjusted rate ratio was  1.01 (0.86─1.19) and \nwas not statistically significant.  \n \nAs ment ioned earlier, much of the vaccination with the Pfizer -BioNTech bivalent booster was  \noccurring at the same time as peak influenza vaccination in the VSD  in persons  ≥65 years  of \nage. A  substantial number of the cases  in the risk window also had simultaneous  influenza \nvaccination.  Most of the individuals ≥65 years  of age who had simultaneous  influenza \nvaccination received a high- dose or  adjuvanted influenza vaccine,  which might be expected \nbecause those vaccines are preferential ly recommended.  A stratified analysis was conducted  to \nassess ischemic stroke incidence during the risk window compared to the comparison window \namong persons ≥65 years of age, with and without simultaneous  influenza vaccination. For \nindividuals who received the bivalent Pfizer -BioNTech booster and simultaneous high- dose or \nadjuvanted influenza vaccine, the adjusted rate ratio was elevated but not statistically significant  \nat 1.59 (0.99─ 2.61). The bivalent Pfizer -BioNTech bivalent booster without any same day  \ninfluenza vaccine  had an adjusted rate ratio of 1.01 in February 2023 in the simultaneous group  \nand was statistically significantly elevated.  It is now attenuated and is no longer statistically \nsignificant.  \n \nTo summarize, the statistical signal persisted during the  November to January timeframe. The \nrate ratio has slowly attenuated from 1.92 to 1.26  and has not met signaling criteria during the \npast 10 weekly analyses. Supplemental analyses using an unboosted concurrent comparator  \nshowed a rate ratio of 1.01, which was  not st atistically significant.  Analyses evaluating \nsimultaneous high -dose or adjuvanted  influenza  vaccine showed a rate ratio of 1.59,  which also \nwas not statistically significant. Separate analyses did not detect an elevated rate ratio for stroke \nafter influenz a vaccine alone. In previous presentations,  data from some  supplemental analyses \nsuggest ed comparison interval rates were lower than expected.  There can be several reasons  \nan elevated rate ratio might be seen. There may be more than expected cases in the r isk \nwindow  compared  to the comparison window , less cases than expected in the comparison \nwindow compared to the risk window, or  a combination of two.  Data previously presented in \nFebruary suggest ed that  there was some evidence of a lower rate in the comparison interval \nthan would be expect ed. \n \nMoving on to VAERS. As a reminder, VAERS is the national spontaneous reporting or passive \nsurveillance system  that is co-managed by CDC and FDA.  This system is good at rapidly \ndetecting safety signals  and rare adverse events  (AEs) . As a spontaneous reporting system, its \nmain limitation is that causality cannot be assessed based on VAERS data alone.  In general \nsummary of US reports to VAERS following bivalent booster COVID -19 mRNA  vaccination  \namong people ≥5 years  as of April 2, 2023 (N=28,363) , the distribution by age, sex,  and serious \nstatus was similar regardless of manufacturer. For both Pfizer -BioNTech and Moderna \nvaccines, 93% of reports were non -serious . That is consistent  with what  has been observed with  \nother monovalent booster vaccinations.  \n \nIn terms of r eports to VAERS of ischemic stroke or transient ischemic attack (TIA) after  bivalent  \nCOVID -19 mRNA vaccination in people ≥18 years  of age after bivalent vaccination as of April 2, \n2023, there were 252 preliminary reports of ischemic stroke or TIA.  Of these, 34  are still under \n11 \n review , 9 were excluded based on chart review , and 60 were non- ischemic strokes verified by \nchart review. That left a total of 149 verified reports of ischemic s troke or TIA comprised of 110 \nischemic strokes, 35 TIAs, and 4  ischemic stroke + TIA. There are 112 Pfizer BioNTech bivalent \ncases and 37 Moderna  bivalent  cases.  The m edian age was 72 years, median time to onset \nwas 13 days, 68 were in males and 81 were in females.  All 149 verified reports had at least 1 \nrisk factor for ischemic stroke, with the most common being hypertension.  Some of these cases  \nreceived simultaneous  influenza vaccination. In those 18─64 years of age, 6 had simultaneous \nadministrati on with standard dose influenza vaccine . Among those ≥65 years  of age, 1 had \nhigh- dose, 3 had adjuvanted, 2 had standard dose, and 1 had an unknown type of influenza \nvaccine. This table show s VAERS reports and reporting rates of ischemic stroke and TIA in the \n3 weeks  after bivalent vaccination people 18─ 39, 40─ 64, and ≥65 years  of age:  \n \n \n \nThis is limited to reports with onset within the  3 weeks , so the observed reports are the verified \nVAERS reports in these specific age and vaccine strata.  The chart verified reports plus reports \nunder review  is essentially a sensitivity analysis  in which the reports under review are  assumed \nto be  true reports.  The easiest way to explain this ,  focus ing on the bottom row, this is saying \nthat within in a hypothetical cohort  of individuals ≥65 years  of age ( 9.6 million individuals ) about \n3,500 stroke or TIA cases would be expected in a 3 -week  period.  The background rates are \nbased on the references at the bottom of the table. These are t hese observed versus  expected  \ncases, which  require s some assumptions.  While this is not a perfect analysis, it does provide \nsome perspective on what is being observ ed compared to what would be expect ed based on \nbackground.  To provide some information on stroke in general from  CDC statistics, about every \n40 seconds someone in the US has a stroke and about every 3.5 minutes somebody dies from \na stroke.  About 87% of strokes are ischemic strokes.  In this analysis,  no unusual or unexpected  \nreporting patterns were observed and no ev idence of a safety concern  was detected for \nischemic stroke  with either mRNA COVID- 19 bivalent booster in VAERS monitoring.  \n \nIn terms of COVID -19 mRNA bivalent booster vaccination safety  data from other monitoring \nsystems and programs,7 FDA monitoring in the Center for Medicare and Medicaid Services  \n(CMS ) data and Department  of Veterans Affairs  (DVA)  monitoring in the Veterans Affairs ( VA) \nsystem have not detected any safety signals  using historical comparator designs. Surveillance \nconducted by i nternational regulatory  and public health partners have not detected a safety \nconcern for ischemic stroke.  There is no evidence of a safety signal for ischemic stroke in \n \n7 Note: These surveillance activities did not include analyses to evaluate the effect of simultaneous flu vaccination; different \nformulations of COVID -19 mRNA bivalent booster vaccinations were used globally . \n\n12 \n Pfizer ’s global monitoring of COVID boosters . No safety signals were dete cted for ischemic  \nstroke for primary series or monovalent boosters for Pfizer -BioNTech or Moderna vaccines in \nUS and global monitoring.  \n \nIn terms of further evaluation, CDC will continue to consult with other surveillance systems to \nbetter understand the possible role  of simultaneous high- dose or adjuvanted influenza \nvaccination with COVID -19 vaccination, as well as the possible decreased rate of stroke \nobserved in the VSD in the 3 to 6 weeks following vaccination. CDC is in the process of chart \nreviewing a random sample of 100 cases across VSD sites and will continue to monitor VAERS.  \nCDC continues to recommend that everyone eligible for a COVID -19 mRNA bivalent booster or  \ninfluenza vaccine get vaccinated.  CDC and FDA are engaged in epidemiologic analyses  \nregarding simultaneous vaccination with COVID -19 mRNA bivalent booster  and influenza \nvaccines.   \nv-safesm After Vaccination Health Checker  \n \nTom T. Shimabukuro, MD, MPH, MBA (CDC/NCEZID)  next presented an update on the v-\nsafesm after vaccination health checker , including a brief overview of v- safesm, contributions of v-\nsafesm to the COVID -19 response, data on historical and current participation in v- safesm, \nplanning for the wind- down of the current system  and the development of the next version of  v-\nsafesm, and continued safety monitoring of COVID -19 vaccines.  As a reminder, v -safesm was \nimplemented in December 2020 . It was designed to collect near real- time data by direct  \noutreach to vaccine recipients.  It was initially conceived to rapidly collec t basic safety data  (e.g., \nprimarily local and systemic reactogenic and health impacts ) at the onset  of the COVID -19 \nvaccination program to provide early data while other systems like VAERS and the VSD were \naccruing data.  In addition, v -safesm identified vaccinated pregnant persons for possible \nenrollment in the COVID -19 Vaccine Pregnancy Registry.  It also was u seful in rapidly collecting \nearly safety data when authorizations and recommendations expanded to other age  and risk \ngroups. It was quickly adapted to capture simultaneous administration  of other non- COVID  \nvaccines  (e.g., influenza vaccine) . It was designed, built, and supported in collaboration with \nOracle Health Services under a donation agreement with  the Department of Health and Human \nServices (HHS ). \n Enrollment  in v-safe\nsm is by self -registration on a smartphone, with any dependents added  to a \nguardian’ s account. Survey completion was prompted by text message reminders  for “health \ncheck -ins,” which had links to online surveys. Call follow -up was performed on all participants  \nwho reported a medically attended event. There was robust participation in its first year,  with 9.3 \nmillion participants and 131 million health surveys completed.  Total participation to date has  \nincluded 10.1 million participants and 151 million health surveys completed.  Most of the \nregistration and most  of the health surveys occurred in the first year.  v-safesm has been \nparticularly effective  in characterizing the basic safety of COVID -19 vaccines during early \nvaccine i ntroduction and following new authorizations and recommendations. v- safesm has \nsuccessfully accomplished his mission  and worked as intended. This graph shows participation \nin v-safesm over time : \n  \n13 \n  \n \nGenerally, registra tions  paralleled doses administered. As noted earlier, most new v -safesm \nregistrations and survey  completions occurred in the first year  of the vaccination program.  Use \nhas waned rapidly and has pretty low uptake at this point. Also noteworthy is that active  \nregistra tion and  doses administering paralleled early on when many doses  were  administered. \nThen there were peaks in doses administered largely represent ing new authorizations  \nand recommendations. However, there was not a corresponding surge in v -safesm uptake with \nthese new registrations. There probably were a lot of early adopters early  in the program, which \nis not totally unexpected.  \n It is important to understand what v -safe\nsm is and is not. v -safesm was designed to rapidly \nmonitor  and assess common outco mes (e.g., local and systemic reactogenicity and health \nimpacts )—the basic safety profile of the vaccine. It is not designed to be a signal detection or \nsignal assessment system. Those systems  are primarily VAERS , VSD, FDA's Biologics \nEffectiveness and Safety (BEST) System, and FDA , CMS,  and VA  active surveillance systems.  \n \nIn terms of the next step for v- safesm, the timing for the final registration and completing of  \nsurveys will be announced soon.  Follow -up will continue on reports of medically attended health \nevents. The next generation v- safesm is under development.  CDC plans to collect data on new  \nvaccines. Once developed and implemented,  the new  v-safesm will allow greater flexibility for \nsurveys and use  of CDC information technology (IT) infrastructure.  It will be designed to permit  \nlonger -term support for collecting data rapidly from a large number  of vaccine recipients.  v-\nsafesm is one of the several compl ementary systems at CDC and one of many compl ementary \nsystems that the US G uses to monitor vaccine safety. CDC’s  standard established systems will \ncontinue to monitor  and assess the safety of COVID -19 vaccines. That includes VAERS, the \nVSD, and the Clinical Immunization Safety Assessment (CISA) Project.  \n \nDiscussion Points  \n Dr. Virginia Caine (NMA) observed that according to the VAERS data, Blacks have a 50% \ngreater stroke incidence than their White counterparts  and asked whether stroke incidence side \neffects data were broken down by race and ethnic populations  to understand whether there \nwould be higher risk among Blacks over the age of 65 . \n \n\n14 \n Dr. Shimabukuro indicated that data on race and ethnicity are collected in V AERS, but because \nVAERS is passive, the data on these variables is dependent upon the reporters  filling in that \ninformation.  While the data are not analyzed by race and ethnicity, these data are collected . \nThis information is also collected in the VSD, but the ability to analyze at that level  is limited in \nthe VSD because of small numbers. He acknowledged the importance and said that \nconsideration can be given to exploring ways of getting better visibility  on race and ethnicity. At \nleast for the VSD RCA,  race and ethnicity  are not the primary variables in the RCA because the \nfiner the data are sliced , the greater the small numbers problem.  \n \nWhile he was glad the signal had not persisted and that there would be continuing \nepidemiologic analyses regarding simultaneous  vaccine with the high- dose influenza and  \nCOVID bivalent booster, Dr. Sanchez asked if any changes were anticipated in the \nrecommendation that they can be administered simultaneously or if there should be a cautionary note saying that there should be an interval of separation between the tw o. \n Dr. Shimabukuro said he did not think the data were sufficient to conclude that there is a safety  \nproblem for ischemic stroke with the Pfizer vaccine in this age group,  or that there  is a safety  \nproblem with simultaneous administration  of COVID and influenza vaccines. Additional w ork is \nbeing done. FDA has a study in progress and CDC  and its VSD partners will continue to \nevaluate the data.  At this time, the feeling is that the data are  not sufficient to conclude that \nthere is a safety problem  requiring make a change in recommendati ons. \n Dr. Lee  reflect ed on the importance of sustaining these vaccine safety surveillance efforts  \nbeyond COVID -19. She reminded everyone that during H1N1, there was a similar effort in place \nakin to v-safe\nSM to monitor safety rapidly with the initial imple mentation of H1N1 vaccines, but it \nwas difficult to sustain.  With COVID -19, it was not clear how v -safeSM would be able to \ncontribute.  However, it has been quite impactful—especially for pregnant populations.  She \nexpressed gratitude to CDC for continuing t o sustain important and compl ementary safety  \nsurveillance tool for the future.  It gave her confidence and she found it incredibly reassuring  that \nbased on the number  of compl ementary systems at CDC for vaccine safety and in partnership \nwith other federal agencies  (FDA, DoD, IHS, VA, and others ) that ACIP is are able to emphasize  \nthe importance of vaccine safety to vaccination programs.  \n \nCOVID -19 Vaccine Effectiveness Updates  \n LCDR Ruth Link -Gelles, PhD, MPH  (USPHS/CDC)  presented  a summary  of vaccin e \neffectiveness data available from CDC studies, including VE of the original monovalent vaccines  \nand updated bivalent vaccines.  This included presentations on  updated estimates  of VE of \nmonovalent vaccines for symptomatic infection in young children aged 6 months –4 years \n(Pfizer -BioNTech) and 6 months –5 years (Moderna ), as well as an update on monovalent and \nbivalent VE against severe disease in adults with  and without immunocompromising conditions.  \nFor background,  she shared the national coverage estimates from CDC’ s COVID  Data Tracker\n8 \nfor the primary series among young children showing that young children have the lowest  \ncoverage for either a single dose or a completed primary series , with just over 10% for 1 dose  \nand 6% for the complete primary series in children  2 to 4 years  of age . Coverage is even lower  \namong those under 2 years of age. Children vaccinated early may be meaningfully different  \nfrom those who remained unvaccinated, which may impact VE estimates.  \n  \n \n8 https://covid.cdc.gov/covid -data- tracker/#vaccination -demographics -trends   \n15 \n The Increasing Community Access to Testing (ICATT) platform includes community -based \ntesting data from pharmacies and partners nationwide.  It uses a test -negative design with self -\nreported vaccine history at the time of test registration.  For th ese analys es, only children whose \ncaregivers reported symptoms and who were between the ages of  3 and 5 years for the \nModerna analyses and 3 and 4 years of age  for the Pfizer -BioNTech analyses were included.  \nChildren whose caregivers reported that the child being tested had immunocompromising \nconditions were excluded.  These data are for tests from July 4, 2022 through April 8, 2023,  \nalthough the analysis start date varied  depending upon the dose analyzed.  This was a period \nwhen Omicron BA .4/BA.5 and XBB related sub- lineages predominated.  \n \nLooking at preliminary estimates of VE against symptomatic infection for monovalent Moderna \nvaccine among children 3 to 5 years of age, VE was 40% (95% CI: 25 -52) for 1 dose  or a partial \nseries during the interval between the first and se cond doses.  VE for the complete 2 -dose \nprimary series of  Moderna was  47% (95% CI: 37 -54) over the entire  2 weeks to 6  months after \nthe dose.  Broken down by time since dose, VE decreased from 61% (95% CI: 47 -71) during the \nfirst 2 weeks to 1 month  after the dose to 18%  (95% CI: -6-37), with confidence intervals \ncrossing the null during the 4 to 6 months after the dose.  Looking at the same information for \nPfizer -BioNTech in children 3 to 4 years  of age  for a 1 -dose partial  series,  VE was 20% with a \nconfidence interval that just crossed  the null  (95% ci: 0 -36). For 2 doses, which for Pfizer -\nBioNTech also is a partial series, VE was 40%  (95% CI: 28 -50) in the interval between doses 2 \nand 3.  For 3 doses, a complete Pfizer -BioNTech primary series,  VE was 27%  (95% CI; 4- 45) in \nthe 2 weeks to 6 months  after the dose. There was not enough statistical power to break  down \nthe Pfizer - BioNTech complete series estimates by time since last dose.  \n \nThere are a number of limitations for this analysis. As  noted earlier, vaccine coverage is low  in \nchildren 5 years of age and under. When coverage is low, vaccinated children may be  \nmeaningfully different than unvaccinated children , potentially biasing early VE estimates and  \nmaking the estimates less stable. The prevalence  of prior infection among children is high.  \nBased on CDC seroprevalence data through December 2022,  more than 92% of children  6 \nmonths through 17 years of age had a prior infection.  If unvaccinated children have protection \nfrom prior infection, it may lead to an underestimation of VE.  However, the prevalence of prior \ninfection is so high that these estimates are likely  to represent the current situation among \nyoung children in the US. While the goal of the US COVID -19 vaccination program is  to prevent \nsevere disease, the ICATT platform estimates VE for symptomatic infection only.  To date, l ow \nvaccination coverage in this age group has p revented estimation of VE against more severe \ndisease. However, other VE platforms may impact future ability to estimate  VE in this group,  \nincluding against severe outcomes.  Given this context, VE against symptomatic infection can  \nprovide important insight into vaccine protection.  \n \nIn conclusion,  a complete monovalent primary series vaccination helped provide protection for  \nchildren 3 through 5 years of age against symptomatic SARS -CoV-2 infection for at least the \nfirst 3 months after vaccination. Some waning of the monovalent Moderna primary series  \nappears  to occur by 4  to 6 months after the second dose. These patterns are similar to patterns  \nobserved in older children and adults in the first months after vaccination. Waning of  \nmonovalent Pfizer -BioNTech against symptomatic infection could not be assessed, but also is \nlikely based on analyses in older children and adults.  Children should stay up- to-date with  \nCOVID -19 vaccines . CDC will continue to monitor VE in this age group,  including against severe \ndisease and for bivalent doses if possible.  \n  \n16 \n Moving to updated estimates of bivalent VE against ED and u rgent care (UC)  encounters  and \nhospitalizations in adults 18 years of age and older , the VISION VE Network  is a multi- state  \nnetwork based on EHRs. Like ICATT, it uses a test -negative design with cases having COVID -\nlike illness and a positive PCR  for SARS- CoV-2 and controls having COVID -like illness (CLI) \nwith a negative PCR. VE is adjusted for age, sex, race, ethnicity,  geographic region, calendar \ntime, and local rates of SARS -CoV-2 circulation.  Vaccination is determined via EHRs  and state \nand city registries.  In terms of the absolute VE of monovalent and bivalent vaccines against  ED \nand UC encounters among i mmunocompetent adults  among adults 18─ 64 years of age and \n≥65 years of age, for those who received only monovalent doses, roughly a year has passed \nsince their last dose.  For those receiving bivalent doses, the time since last dose is  much \nshorter.  For monovalent doses, there is little remaining protection.  For bivalent  vaccination, the \ntrends across the age groups are similar with bivalent VE at 53% (95% CI: 48 -58) for adults \n18─64 years of age and 61% (95% CI: 57- 64) for adults ≥ 65 at 7 to 59 days after the first dose. \nEstimated VE declines by 120 to 179 days  after the bivalent dose to 15% (95% CI: 2- 26) for the \nyounger group and 25%  (95% CI: 16- 34) for the o lder group.  \n \nFor hospitalizations, there was s ome residual protection.  In contrast to the ED , effectiveness of \na monovalent dose was  21% (95% CI; 10- 30) for younger adults and 25% (95% CI: 18- 31) for \nolder adults.  For bivalent doses, trends were similar across age groups . However, there was not \nenough statistical power  to interpret  estimates for 120 to 179 days out from the bivalent dose in \nthe younger group.  In older adults, there was waning at a higher point estimate than against \nED/UC encounters.  Regar ding absolute VE of bivalent booster doses  against hospitalization \namong immunocompromised individuals ≥ 18 years of age, there was little remaining residual \nprotection of the monovalent vaccine.  VE estimates for bivalent vaccines start ed lower  than for \nthose of immunocompetent individuals at 30%  (95% CI: 12 -44), but the same patterns  of waning \nhave not been seen in this group thus far.  \n \nTo provide a snapshot of who is being hospitalized with COVID -19 and the VISION VE Network , \nit is important to note that this analytic population does not match the population used in the VA \nanalysis precisely . It does give an overall sense of who is being hospitalized and who has  \ncritical illness defined as “admission to intensive care or in- hospital death  within the VISION \nNetwork.  The median age is approximately 75 years . Eighteen percent of those hospitalized and \n24% of those with critical illness had an immunocompromising condition. This is compared to \nroughly  3% in the overall US population.  Thirty percent of those in the hospital and 34% of those  \nwith critical illness are entirely unvaccinated, which is particularly notable when considered along with the median age of this population and the fact that in the US as a whole, 94% of \nthose aged 65  and up have completed at least a primary series.  Also notable is t hat 17% of \nthose hospitalized and 15% of those with a critical hospitalization had received a bivalent  \nbooster  compared to about 43% of the overall US population over 65 years of age.  \n \nThe next update is on data published by CDC in December  2022 looking at the effectiveness  of \nthe bivalent boosters against hospitalization in adult s ≥65 years of age through the Investigating \nRespiratory Viruses in the Acutely Ill ( IVY) Network , which is a multi- state VE platform  that uses \na prospective test -negative design. For this analysis, participants were  enrolled from 25  \nhospitals  in 20 states with hospitalization between September 8, 2022 and April 1, 2023. Note \nthat this analysis includes data beyond what was published in the MMWR  in December  2022 . \nParticipants are adults hospitalized with COVID -like illness. Cases have a SARS -CoV-2 positive \nPCR or antigen test  and controls are negative for SARS -CoV-2 and influenza by PCR.  Models  \nare adj usted for age, sex, race, ethnicity, admission date, and HHS region.  \n  \n17 \n In terms of updated  IVY results among adults ≥65 years of age for  absolute VE against \nhospitalization, comparing people with at least 2 monovalent doses but no bivalent dose to \nunvaccinated people , VE was 13% with a confidence interval crossing the null  (95% CI: - 9-30). \nThis is  consistent  with the limited to no residual protection of the monovalent doses. Absolute \nVE of a bivalent booster follow ed a similar pattern , with high initial pro tection and apparent \nwaning.  Looking at the r elative VE of a bivalent booster comparing individuals  who received a \nbivalent booster to individuals with at least 2  monovalent doses but no bivalent booster , the \nadditional protection offered by a bivalent booster  was 60% (95% CI: 45- 71) with waning \napparent  with more time since the dose. Note that as with the VISION estimates , the median \ntime since last dose was  over a year  for monovalent only recipients.  \n \nRegarding the durability of monovalent VE protection against the most critical illness,  invasive  \nmechanical ventilation (IMV)  and death among adults ≥18 years of age in the IVY Network, this \nanalysis assessed VE of 2 to 4 monovalent mRNA vaccine doses against IMV  or death among  \nimmunocompetent adults  ≥18 years of age through January 31, 2023.  Overall, this group is  at \napproximately 8 months  since their last monovalent dose.  For the overall group, VE was  62% \n(95% CI: 52- 70) against critical illness.  This does not vary substantially by age group.  VE \nstarted at 76%  (95% CI: 66- 83) in the first 179 days since the last monovalent dose, with \nevidence of waning early on. However, that VE at a median of 455 days or about 15 months  \nsince the last dose remained relatively high at  56% (95% CI: 36- 69), showing the lasting \ndurability of COVID -19 vaccines  against the most critical illness.  Looking at these same data \nbroken down by time  since last dose of 7 to 179 days or 180 plus days  and number of \nmonovalent doses received,  there was a  slight decline  in VE by tim e since last dose, but \nsustained protection overall against the most critical illness.  Substantial variation is not seen by \nnumber of doses received in either the earlier  or the later  period.  \n \nThe results  presented from both the VISION and IVY  VE Networks have  several limitations.  \nRegarding the estimates of absolute VE, if unvaccinated individuals are meaningfully different \nthan vaccinated individuals, estimates may be biased.  For interpretation  of estimates of relative \nVE, residual protection from prior doses is an important  consideration and likely varies by \nseverity of outcomes studied.  There is limited information on prior infection,  \nalthough just as with young children, rates of prior infection in adults and older children are  \nknown to be high.  Therefore, the VE estimates presented during this session represent a \nsnapshot of how well the vaccine is working under current conditions.  Finally, VE against \nCOVID -19-associated hospitalization from the  IVY and VISION platforms represent individuals  \nhospitalized with COVID- 19 disease, but may underestimate protection against critical illness.  \n \nIn summary, current data from CDC  VE platforms demonstrate  that bivalent booster doses \nprovide added protection compared to earlier monovalent doses  against ED  and UC encounters \nand hospitalizations  in adults, though there is evidence of waning protection.  For most adults,  \nboth in the platform s shown and in the general population, more than a year has passed  since \nthey last received a monovalent COVID -19 vaccine.  These individuals may have limited residual  \nprotection against hospitalization and should receive a bivalent booster dose. However, results \nfrom the IV Y analysis show durability  of protection against the most critical COVID -19 disease \nrequiring IMV or causing death. CDC will continue ongoing monitoring of VE, including for all  \noutcomes of interest  and for all authorized vaccines in the US, including Pfizer, Moderna, \nJanssen, and Novavax, with a focus  on assessing new policy recommendations and VE in \npopulations at higher risk of severe COVID -19 disease.  \n  \n18 \n Discussion Points  \n \nDr. Chen  inquired as to why the original Wuhan strain was being included in the vaccines, given \nthat there is evidence the more recent doses are more effective —certainly with the bivalent \nvaccines. This seemed like an opportunity to comment on thoughts about strai n match  and \nselection going forward for the bivalent versus monovalent  vaccines  for mRNA  and other \nvaccine constructs as well.   \nDr. Link-Gelles  pointed out that the goal of this presentation was to summarize what is known \nabout currently available vaccines and that she would defer questions about strain selection and \nthe make- up of current and future vaccines  to later conversations among the ACIP and  \nVRBPAC.  \n Referring to Slide 7 regarding monovalent vaccine, Ms. Bahta  asked whether there were any \ntheories  about why efficacy decreased or was not remarkable after the third dose of the Pfizer  \nBioNTech vaccine and there was no boost at all from the second dose.  \n Dr. Link-Gelles  indicated that it was important to keep in mind  that the confidence intervals  \nbetween the estimates overlap quite a bit  so she was not sure it could be called a decrease . In \naddition, the time for follow -up is quite a bit different.  For the 2- dose estimate, the analysis \nlooked only at  the interval before the third dose out to 3 months. The estimate for the third dose \ngoes out to 6 months.  That was because there were not enough children who received all 3 \ndoses, so there was not enough power to break it down by time since dose.  Therefore, the third \ndose is g etting dinged  for having more extensive follow -up time.  It is known from older children \nand adults that VE against symptomatic infection wanes by time since dose.  If there were \ncomparable follow- up times after the second and third doses, the point estimates probably  \nwould be more comparable.  \n Referring to Slide 14 regarding hospitalization among immunocompromised adults  ≥18. Dr. \nKotton observed that while there was some overlap in the various timeframes  that showed \npotential waning, it was not as much as might have been expected. She asked if there were any \nthoughts about this, especially in the context of considering another bivalent booster  for th e \nimmunocompromised population ≥ 18. \n Dr. Link-Gelles  said she thought in part this was a precision issue, especially at the furthest  \nfollow-up time  where the confidence interval  was quite wide and there may be missing waning \njust because of that.  In addition, the immunocompromised populations being studied in these \nplatforms are fairly heterogeneous  and includes the span of potential immunocompromise.  It is \nknown from earlier studies that the vaccine works much better  in some immunocompromised  \npopulations and worse in others, such as bone or organ transplant recipients.  In this case, \nbecause of precision issues, there are not enough data to break it  down by type of  \nimmunocompromise d. What this analysis was showing probably  was the result of a relatively \nheterogeneous group combined with those that who probably are at highest risk of severe \nCOVID  being earlier adopters probably having different numbers  of monovalent doses  \npreviously received , and different times since those monovalent doses previously received.  \nWhat she would read from this comparison  to immunocompetent individuals was  that VE is  \nlower at the beginning in immunocompeten t individuals  and similar patterns of waning would be \nobserved if broken down by some of the variables mentioned previously, which has not been possible due to precision.  \n  \n19 \n Dr. Long  observed that there did not seem to be much evidence of herd protection. With the \neffects of bivalent vaccine boosters apparently being modest  and short -lived based on these \nanalyses, it seemed the hope with this kind of vaccine and disease the hope would be to protect \nagainst death and mechanical ventilation.  \n \nDr. Link-Gelles  agreed that the goal of the COVID -19 vaccination program is  to prevent severe \ndisease, including hospitalization and the critical outcomes discussed.  VE for symptomatic  \ninfection has been shown in cases where there is a lack of data to show VE against more \nsevere illness.  This presentation showed VE for symptomatic infection in young children \nbecause to date, there has not been sufficient s tatistical power to assess that against sever e \ndisease.  \n \nRecognizing that  there is a very small proportion of the population vaccinated and that it is \ndifficult to assess effectiveness with the small numbers, Dr. Long asked whether the vaccine manufacturers and possibly FDA  could comment on post-mark et Phase 4 studies  that might \naddress effectiveness in these populations. There continues to be a strong need for additional \ndata on the levels in durability of protection for children, pregnant people,  and \nimmunocompromised populations. \n \nDr. Rituparna Das  from Moderna  responded that the effectiveness work  is ongoing within the \nKaiser Permanente Southern California Health System.  Moderna presented some early data on \nbivalent effectiveness  in adults during the January  2023 VRBPAC meeting and hopes to receive \nan update soon on pediatric VE and the immunocompromised.  As noted, the ability to do this  \nwill depend on the uptake in that system.  \n \nAlejandro Chevalier from Pfizer  indicated that Pfizer also is working with Kaiser Permanente  \nNorthern California and are seeking to bring the data soon.  \nUpdates to COVID -19 Vaccine Policy: Considerations for Future Planning  \n Sara Oliver, MD, MSPH (CDC/NCIRD)  first re viewed COVID vaccine uptake over time, pointing \nout that the overall population received vaccine shortly after recommendations have been  \nupdated, but uptake overall has declined over time with additional vaccine recommendations.  In \nterms of current vaccination coverage  by vaccine and age group, 1 6.7% of the population \noverall has received a bivalent booster  dose to date, with higher coverage in older age groups.  \nHowever, even among adults ≥65 and over , over half of the population has  not received a \nbivalent dose to date.  Regarding trends in variant proportions over time, the most recen t \nsurveillance shows that most isolates are related to the XBB sub- variant. Even with the newer \nvariants , there has not been a larger increase in cases as seen in previous years.  Looking at \noverall hospitalization rates by age from COVID -NET, the highest hospitalization rates continue \nto be among older adults.  \n Building on what was discussed in February  2023, the goal is simple recommendations. \nAspects of this include how frequently people should get a COVID vaccine and groups or \npopulations who may benefit from possibly more than one vaccine a year.  During this session, \nDr. Oliver discussed steps toward simple recommendations, noting that this is a journey that \nlikely will include several steps.  In terms of a single formulation for mRNA COVID- 19 va ccines, \na single annual dose  possibly will be needed for most individuals , with flexibility for vulnerable \npopulations.  It is important to note that many of the monovalent COVID -19 vaccine products  \nalready  have expired and others will expire soon.  FDA has removed the authorizations from  \nmonovalent mRNA COVID19 vaccine products  and harmonization across the recommendations \n20 \n with the bivalent mRNA COVID- 19 vaccines was discussed at the VRBPAC  meeting in January \n2023 and the ACIP  meeting in February  2023. B oth a dvisory committees expressed support.   \n \nTo summarize data that  have been presented during previous ACIP meetings , the bivalent \nCOVID vaccines are able to induce an immune response, whether given as a primary series in \nindividuals who are previously unvacci nated or when given as a booster dose.  When given to  \nunvaccinated children, the immunogenicity data of a BA.1 vaccine induced antibody titers to  \nBA.1  that were 25 times higher than the original monovalent vaccine. The percent of patients \nwho reported local  or systemic events were similar to or less than what was seen after the  \nmonovalent vaccine.  However, this may be a result of the larger percent of seropositive \nparticipants in the bivalent vaccine group . There are limited data to directly compare  COVID -19 \noutcomes after a monovalent versus a bivalent vaccine.  Most studies showed an improvement \nin neutralizing antibodies for Omicron variants with a bivalent vaccine.  However, it is difficult to \ncorrelate  that improvement to defined clinical outcomes. W hen evaluating antigen cartography  \nthat was presented in September  2022 , the bivalent vaccines expanded the immune response \nand provided increased diversity in antibody response.  Data  from a United Kingdom ( UK) study  \nfound around a 10% increase in VE for COVID -19 infections  with a bivalent vaccine.  The \ntransition will reduce the mRNA products from 11 vials to 5  vials and will eliminate the lookalike \nvials between the monovalent and bivalent products.  \n \nTo summa rize discussions from the last ACIP meeting, receiving COVID -19 vaccine s continues \nto be important for prevention of COVID -19 severe disease,  hospitalization, and death. \nHowever, many children and adolescents remain unvaccinated for COVID.  COVID -19 vaccine \nrecommendations that are simple to implement may remove some barriers to uptake.  Overall, \nACIP was supportive of a transition of the mRNA COVID -19 vaccine primary series  from \nmonovalent to bivalent vaccines.  As discussed earlier , FDA removed the authorization from  \nmonovalent mRNA products.  The BLAs are still in place, but the vaccines are either expired or \nhave very limited doses in circulation.  At this point, the bivalent mRNA COVID -19 vaccines are \nnow authorized for all indications and there were no changes to the current language in the \nother COVID -19 vaccine authorizations , such as Novavax  or Janssen COVID -19 vaccine s. In \nterms of what this all mean s for CDC recommendations , a transition to bivalent COVID -19 \nvaccines could simplify presentations,  reduce  errors, and allow continued access for vaccine \nwith the expiration of monovalent products.  Bivalent mRNA COVID vaccines would now be  \nrecommended for all indications.   \n \nThe next step toward simple recommendations  perhaps would be a single annual dose for m ost \nindividuals.  Looking at data from blood donors  to assess the proportion of the population by type \nof immunity and how they  have transitioned over time, the proportion has continued to decline \nover time.  Overall, h ybrid immunity  has increased over time.  Separated out by age groups , \nthere are 2 things to note. The proportion w ith no prior infection or vaccination is low across all \nage groups  in the most recent data. The proportion with hybrid immunity , which may at this point \nprovide the strongest pr otection, is actually the lowest in that oldest age group.  Highlighting \ntiming for increases in cases or hospitalizations , overall increases have been seen during the \nwinter months , due to the emergence of new escape variant s, or when both have occurred at  \nthe same time.  \n  \n21 \n To summariz e previous discussions  regarding the possibility of a single annual dose, future \ndoses for most people would be an additional boost after prior infection, prior vaccination, or \nboth.  An update to the benefit -risk analysis  shown in February demonstrated that time since the \nlast COVID -19 vaccine dose may both increase the incremental benefits of a COVID vaccine \nand decrease the risk of myocarditis.  As shown by VE studies, vaccine protection likely declines \nover time.  Winter months  and immune escape variants have impacted COVID -19 epidemiology.  \nIt is known that a simplified annual recommendation could help reduce vaccine and message \nfatigue.  A plan for a fall booster dose could provide added protection at a time when many  \nwould be about a year from their last dose.  The future epidemiology in SARS -CoV-2 virus  \nevolution could help determine the need  for continued annual boosters.  \n \nAgain, FDA authorized a single age- appropriate dose of mRNA COVID -19 vaccine for most \nindividuals . A singl e age- appropriate dose of a bivalent Moderna COVID -19 vaccine is \nauthorized for individuals ages 6 years and older who are unvaccinated, or at least 2 months \nafter receipt of any monovalent COVID -19 vaccine.  A single age- appropriate dose of a bivalent \nPfizer COVID -19 vaccine  is authorized for individuals ages 5 years and older  who are \nunvaccinated,  or at least 2 months after receipt of any monovalent COVID -19 vaccine.  \n \nSchool children nearly all have had prior infection,  vaccine -induced , or hybrid immunity.  The \nproportion with immunity is lower in the youngest age groups.  Based on these and other data, \nsome populations of young children likely still need a prime and a boost to optimize immunity.  In \naddition, young children will continue to age i nto the vaccine recommendations at 6  months  and \ncould be SARS -CoV-2 naïve . Additional data are forthcoming  to evaluate the benefits of a multi -\ndose primary series in all children ages 5  and younger,  or if those recommendations could be \nsimplified further. The WG looks forward to presenting a cost -effectiveness  analysis in children  \nand additional antibody data in children during f uture ACIP meetings.  In the pediatric population, \nFDA has authorized 1 , 2, or 3 doses of a bivalent vaccine for  children  6 months through 4 or 5 \nyears.  The number of doses depends on age and the number and type of prior COVID -19 \nvaccines received.  \n \nThe overall implications for CDC recommendation s are that a COVID -19 vaccine framework for  \na single dose could be easy for COVID -19 vaccine providers to implement  and for the public to \nunderstand. The current recommendation for a single dose may evolve over time and could \nmove to an annual recommendation. With these updates, a single bivalent dose would be \nrecommended for everyone ages 6 years and over. For most people, the implication of this \nupdate means no change, and. the actions taken after this are exactly the same.  If someone \nhas not received a bivalent vaccine yet, they  are recommended to receive one regardless  of \ntheir previous vaccine history. C hildren  6 months through 5 years  of age would receive at least \n2 COVID -19 vaccine doses , including at least 1  bivalent vaccine.  Detailed guidance for this will \nbe published in the I nterim Clinical Considerations.  \n \nIn terms of fl exibilit y for vulnerable populations, the rates of hospitalization for those 65 years of \nage and over have seen several increases over the past year.  Unlike what was seen previously \nin the pandemic, these increases have not been near ly as high in the other younger  age groups \nas they were earlier.  However, rates of COVID -19 death  by vaccination status among older  \nadults 65─ 74 years of age and ≥ 80 years of age are highest among the unvaccinated and \nlowest are among those with an updated or bivalent booster dose.  Many  adults who already  \nreceived a bivalent booster dose  were eager for the option to receive another one. In a survey \n22 \n of boosted adults in January,9 over half said that they were awaiting new guidelines for \nadditional doses and 86% said that they felt it was an important or top priority  to receive \nadditional doses. While it is know n that many in the population are experiencing vaccine fatigue, \nthere is a subset who are eager to continue to receive additional doses.  \n \nTo summarize overall  what was discussed in February, it is known that older adults continue to \nhave higher rates of hospitalization than younger adults. Among older adults, vaccination rates  \nwith bivalent COVID -19 vaccines remain low and it is known that it is critical for older adults to \nbe up- to-date on current recommendations, including receiving a bivalent booster. ACIP  \ndiscussed that at the time, the data were insufficient  to support a routine recommendation for  \nolder adults to receive a COVID vaccine dose every 6 months long- term,  but acknowledged that \nthe population may continue to be more vulnerable to severe COVID -19 and likely needs  \nflexibility with COVID -19 vaccine recommendations.  Updates from FDA ’s authorizations for \nadults ≥65 years  of age are that  a single dose of a bivalent mRNA COVID vaccine, either Pfizer  \nor Moderna , may be administered at least  4 months following the first bivalent dose.  In terms of \nimplications for CDC recommendations , bivalent COVID -19 vaccines continue to provide \nprotection against severe disease and rates  of hospitalization or death among adults who have \nreceived a bivalent booster continue to be low.  However, some older adults may  benefit from an \nadditional updated COVID -19 vaccine dose prior  to future recommendations for updated \nvaccines this fall. Adult ≥65 years of age may now choose to receive another updated COVID-\n19 vaccine dose if it has been 4 months since their first bivalent dose.   \n For immunocompromised persons, data  presented in February  showed that \nimmunocompromised adults can have a less robust immune response to COVID- 19 vaccines.  \nUnfortunately, there are no currently authorized prophylactic monoclonal antibody products for \npopulations  at highest risk for COVID -19. ACIP discussed that while the data were insufficient  to \nsupport a routine  recommendation for people who are immunocompromised to receive a COVID \nvaccine every 6 months long- term,  they acknowledged that this population continues to be \nvulnerable and needs flexibility with COVID -19 vaccine recommendations.  FDA has provided \nthat fl exibility. For people who are immunocompromised, additional doses have been \nrecommended previously and current updates continue to allow additional protection to a \nvulnerable population. Updates also allow flexibility to adjust to an individual’s specific  \ncircumstances, including timing of immunosuppression as well as the possible need for re -\nvaccination after particular events (e.g., stem cell transplant) . Additional guidance is to be  \npublished in Interim Clinical Considerations . People who are immunocompr omised may choose \nto receive another updated COVID -19 vaccine dose  and have the flexibility to receive additional \ndoses based on their clinical circumstances.  \n \nTo recap, steps toward the goal  of simple recommendations include the single formulation \nmRNA CO VID-19 vaccines  and a single (possibly annual) dose for most individuals , with \nflexibility for vulnerable populations . However, this cannot be achieved in a single action, so it is \nimportant to acknowledge that future steps may be possible.  While the updates during this \nsession were focused on mRNA vaccines, it may be possible to s implif y all COVID -19 vaccines. \nWhile looking to the possibility of updated vaccines this fall, the WG will continue to evaluate  \ndata- driven ways to simplify the pediatric program and present related data during upcoming \nmeetings. As always, the goal will be to continue to work toward a goal  of flexibility and simple \nguidance.  \n \n \n9 KFF COVID -19 Vaccine Monitor: January 2023. https://www.kff.org/coronavirus -covid -19/poll -finding/kff -covid -19-vaccine -monitor-\njanuary -2023/  A ccessed February 7, 2023  \n23 \n In summary, COVID -19 vaccines continue to be the most effective tool available to prevent  \nserious illness, hospitalization, and death from COVID- 19. Simple recommendations are easier \nto communicate, which may improve uptake.  It is anticipated that an updated fall vaccine could \nbe available. The WG will continue to review data  to inform possible recommendations. Based \non available data at this time , it is anticipated that there would be benefits of COVID- 19 \nvaccines this fall. U pdates to COVID -19 vaccine policy also can acknowledge the  possibility of \nfuture recommendations. For most individuals,  the current doses needed remain unchanged. A \nsingle bivalent vaccine is recommended and there could be an updated vaccine and \nrecommendations this fall.  In direct response to feedback from previous discussions, there is \nflexibility  for vulnerable populations in the current recommendations. Young children continue to \nbe recommended for multiple doses for the prime/ boost immune response. The WG will \ncontinue to review additional data to optimize those recommendations.  \n \nTo summarize the WG discussions  overall: the WG will continue to review data and evaluate the \nCOVID -19 vaccine program in the context  of evolving epidemiology. To date, the COVID- 19 \nVaccine WG has had 112 calls  in which they have reviewed the data and discussed the COVID-\n19 vaccine program. Early COVID -19 vaccine recommendations were made in light of a highly  \nsusceptible immune- naïve population who had limited treatment options.  Increases in \npopulation- level imm unity through vaccine and infection, SARS -CoV-2 virus evolution, \navailability  of antiviral treatments, and the review of COVID- 19 epidemiology and hospitalization \nrates can lead to evidence- based updates  in vaccine policy. This does  not change decisions  \nthat were made then but highlights that the program can continue to evolve as these data  \nevolve as well.  Work will be ongoing to review additional data and continue efforts for \nsimplification.  When reviewing the totality of the data, the WG was supportive of  simplified  \nrecommendations  and flexibility for vulnerable populations. \n \nUpdates to Interim Clinical Considerations for Use of COVID -19 Vaccines \n Evelyn Twentyman, MD MPH (CDC/NCIRD)  presented updates to the Interim Clinical \nConsiderations for the use of COVID -19 vaccines that are anticipated as a result of the \nauthorized revisions the previous day. First, these new recommendations are simple and \nsingular for most people.  The previous recommendations  were for people ages 6 through 11 \nyears without immunocompromise, including specific recommendations  for a primary series and \nbooster , with variation by age and by product.  The new recommendation for people aged ≥6 \nyears  without immunocompromise who have not yet received a bivalent mRNA dose is \nextremely simple:  receive one bivalent mRNA dose  regardless of COVID -19 vaccination history.  \nThe good news  is that vaccination is complete for people who already have received a bivalent \nPfizer or Moderna mRNA dose  and no doses are indicated at this time.  \n \nThe new recommendations also offer flexibility for people at higher risk.  One of the groups of \npeople at higher risk of severe COVID -19 disease is people ages 65 years and older.  People \nages 65 years and older who have not yet received a bivalent mRNA dose  are recommended to \nreceive that dose. Additionally, they have the option of receiving an additional bivalent mRNA \nvaccine dose when  it has been at least 4 months following their first bivalent mRNA dose. That \nmeans that those aged 65 years  and older who  have already received a bivalent mRNA dose, \nfor example, who received their updated booster when they were authorized in September  2022 \nor sometime thereafter, are already up to date.  Vaccination is complete.   \nWith the new flexible recommendations, they have the option  of receiving an additional bivalent \nmRNA vaccine dose when it has been at least 4 months following the initial bivalent dose.  There \nalso is flexibility for people at higher risk of severe COVID -19 disease due to \nimmunocompromise.  For those people aged  6 years and older who have already received a \n24 \n bivalent mRNA dose,  an optional additional bivalent mRNA dose may be administered at least 2  \nmonths after their first bivalent mRNA dose and additional bivalent mRNA doses may be \nadministered as needed.  The changes additionally offer  customized recommendations for \nyoung children as illustrated here. The new recommendations are customized by COVID -19 \nvaccination history  such that all children receive at least 2  vaccine doses in total, including at \nleast 1 bivale nt dose.  This flow chart  was developed to depict how to easily determine what \ncustomized recommendation is  relevant to a child given their personal COVID -19 vaccine \nhistory.  For the Interim Clinical Considerations to be posted to the CDC website, a  complet e \ntable has been developed of the recommendations for vaccine doses moving forward,  given any \nparticular history of COVID -19 vaccination:  \n \n \n \nThe other group of children who have customized recommendations are 5 -year-olds. These \nrecommendations are extremely similar to those for children ages 6  months through 4  years : \n \n \n \n \n\n25 \n  \nTo summarize it means to be up -to-date with COVID- 19 vaccines in the context of the new \nrecommendations , adults and children aged 6 years and older are up- to-date with COVID -19 \nvaccines if they got a bivalent (updated) COVID -19 vaccine.  Children 6 months through 5 years  \nof age who received the Pfizer -BioNTech COVID -19 vaccine are up -to-date if  they are 6 months \nto 4 years of age and got at least 3 COVID -19 vacci ne doses, including at least 1 bivalent \n(updated) COVID -19 vaccine dose or they are 5 years of age and got at least 1 bivalent \n(updated) COVID -19 vaccine dose.  Children 6 months through 5 years of age who got the \nModerna COVID -19 vaccine are up -to-date if they got at least 2 Moderna COVID -19 vaccine \ndoses, including at least 1 bivalent (updated) COVID -19 vaccine dose. Persons may be eligible \nfor additional COVID -19 vaccine doses if  they are 65 years of age and older and got their first \nbivalent (updated) CO VID-19 vaccine booster 4 or more months ago and/or are moderately or \nseverely immunocompromised and received a bivalent (updated) COVID -19 vaccine booster 2 \nor more months ago.  Someone who is unable or chooses not to get a recommended bivalent  \nmRNA vaccine  will be up -to-date if they got the Novavax COVID -19 vaccine doses approved for \ntheir age group.  \n \nIn terms of implications for vaccine providers, the  new recommendations result in fewer total \nCOVID -19 vaccine products in use,  which might be very helpful for vaccine providers. There will \nnow be 5  total bivalent products in use and 1 monovalent product in use. The supply of the 1 \nremaining monovalent COVID -19 vaccine will be expired on May 6, 2023. Additional help for \nproviders i s on the way.  CDC is working to serve providers the very best way possible. Interim \nClinical Considerations are being updated with comprehensive tables of vaccine doses  and \ndosages indicated for each age group, and by history of COVID -19 vaccines received  for \nchildren aged 6  months through 5  years. CDC is working to revise additional clinical guidance \nmaterials and will present these new recommendations and their implications for providers in \ngreater depth during an upcoming Clinician Outreach and Communica tion Activity (COCA)  call \non May 11, 2023.  \n In terms of implications for public health , one of the most important messages  is that although \nthe new recommendations are simplified and although everyone ages 6  years and older will \nnow be up- to-date following  receipt of an updated mRNA vaccine, m ost people in the US have \nnot yet received an updated mRNA vaccine. Just 16.7%  of the entire  US population and just \nover 20% of adults  or 4 out of 5 adults have not  yet received a bivalent mRNA vaccine and are \nnot up -to-date with COVID -19 vaccination at this time.  Bivalent COVID- 19 vaccine coverage \ntends to decrease  with decreasing age . Unfortunately , coverage is not even 50% among people \nages 65 years or older  who may be at higher risk of severe COVID -19 disease because of their \nage. Unfortunately, racial disparities in receipt  of bivalent mRNA vaccines persist . Bivalent \nCOVID  vaccine  coverage is lowest among Black, non- Hispanic , Hispanic /Latino, and N ative \nHawaiian or other Pacific Islander populations.  It also is important to point out that bivalent \nCOVID -19 vaccine coverage is lower among  those with lower income. It is evident that providing \nthese vaccines free of cost to the recipient has not yet resulted  in equitable coverage by \nincome.  Unfortunately, bivalent  COVID -19 vaccine coverage is also lower  among those without \nhealth insurance. It is important to underscore here that a person does not need to have health  \ninsurance in order to receive a bivalent COVID -19 vaccine.  It does appear that there is still work \nleft to be done in achieving equitable coverage for those without health insurance.  \n \nTo provide some reflections and next steps , COVID -19 vaccines continue to be the most \neffective tool to prevent serious illness, hospitalization,  and death from COVID -19. However, \nuptake of the updated bivalent COVID -19 vaccines is not yet equitable and remains generally \n26 \n low. Simple recommendations are easier to communicate,  which hopefully may improve vaccine \nuptake.  CDC is continuing to work toward additional materials  for vaccine providers, clinicians, \nand the general public to make it easy for everyone to get up-to-date and stay up -to-date with \nCOVID -19 vaccines.  \n \nDiscussion Points  (Oliver & Twentyman)  \n \nMs. Bahta  asked whether ethnic  and racial background information related to hospitalization \nand death  are available and expressed concern that there might be  a missing gap of individuals \nwho are vulnerable between 50 to 65  years of age.  \n \nDr. Oliver recalled a presentation in February from the COVID -NET team,  which is where those \ndata come from at CDC. While she did not remember specifically whether those data showed race and ethnicity , she will engage in discussions  looking forward to future meetings to \ndetermine whether additional data can be provided on that.  \nBased on the comments  that have been made via the Federal Registry, Ms. Bahta pointed out \nthat it is important to understand why the recommendations  are not being updated and \nespecially why there is no booster for Novavax.  While Dr. Marks addressed thi s, she thought it \nwas important to re -explain that.  \n Dr. Twentyman indicated that there is a Novavax booster that is authorized in some  situations,  \nspecifically including among those who are unable or unwilling to receive a bivalent mRNA  \nvaccine dose and who have not received previous booster doses. This is part of the  \nauthorization of that vaccine dose and is why it is stated as such. In terms of updating the \nNovavax vaccine itself, she called upon the sponsor to comment.  \n \nDr. Raburn Mallory, Novavax , indicated that they are working to provide an updated vaccine for \nthe upcoming full winter season.  They have been engaged in discussions with the FDA and \nother regulatory authorities about what kind of updates might be made to the vaccine. \n \nDr. Kotton  asked whether the FDA could provide any additional explanation for children who are \nimmunocompromised regarding the number  of vaccine doses that they can receive, which \nseemed somewhat different from what ACIP had been thinking.  In addition, she asked whether \nthere would be additional guidance from FDA or CDC through Clinical Considerations.  While \nshe understand that the intent was  to provide an individual clinician flexibility with some of the \nmore extenuating circumstances, she wondered if there would be any specific language \nprovided regarding that, because as an immunocompromised host  provider, she was not \nnecessarily entirely c lear on what the flexibility actually would provide.  \n Dr. David Kaslow, FDA, indicated that immunocompromised children  and adults  can receive an \nadditional bivalent dose after they  have gotten their first bivalent dose. FDA has provided \nflexibility  for additional doses at the discretion of the HCP  and taking into consideration an \nindividual ’s clinic al circumstances. \n Dr. Twentyman clarified that Moderna recipients ages 6 months through 5 years  of age have the \noption to receive further additional doses  of bivalent Moderna COVID- 19 vaccine as informed by \nthe clinical judgment of a HCP,  personal preference, and circumstances. T hose ages 6 years \nand older who received Moderna  also have the option to receive further additional age-\nappropriate doses of bivalent Moderna COVID -19 vaccine as informed by the clinical judgment \nof a HCP, personal preference, and circumstances.  Pfizer recipients ages 5 years and older  \n27 \n have the option to receive further additional age -appropriate doses of bivalent Pfizer  COVID -19 \nvaccine  informed by clinical judgment, personal preference, and circumstances.  Novavax  \nrecipients ages 12 years and older have the option to receive further additional age- appropriate \ndoses of bivalent mRNA COVID -19 vaccine informed by th e same considerations.  Children 6 \nmonths through 4 years of age who are immunocompromised who received Pfizer are not \nperceived to be authorized at this time.  \n \nDr. Marks  emphasized that the FDA has to make decisions based on data and there were no t \nsufficie nt data to support the  additional dose. Updates will be made when data are available. \nThat means that immunocompromised children  6 months through 4  years of age who had a \nprior Pfizer  dose cannot receive additional vaccine doses moving forward until such t ime as \nFDA has the data , which is anticipated to be toward the fall vaccination campaign once strain \nselection is decided.  \n \nDr. Kotton stressed that this potentially leaves this immunocompromised vulnerable population \nat higher risk  for at least the next 6  months, which sounded potentially devastating for a high-\nrisk immunocompromised population.  Certainly, during the pandemic there have been times  \nwhen the best decisions  have been made at the time based  on the preponderance of data in the \ninterest of publi c health.  She spoke strongly in favor of trying to protect this vulnerable pediatric \npopulation.  \n \nDr. Marks indicated that FDA is happy to take this into consideration and to speak with their \nCDC colleagues.  \n \nRegarding the bivalent Moderna being a lower do se than the primary series, Dr. Lee asked what \nthe potential impact would be now that the lower bivalent dose would be allowed for use as a primary series even though an additional dose is allowed. Immunocompromised children and \nadult patients are presenti ng with severe consequences and have been hospitalized for  \nprolonged periods of time.  For the immunocompromised population,  there are not good choices \nright now or the data to support that it will be possible to optimally protect that population. Given \nthat, she asked what guidance FDA would give providers who are caring for these patients . \n Dr. Marks replied that they allowed the additional dose for Moderna  because of the way \nprevious doses were administered and the situation they were  in. It was a challenge to sort out \nwhat  would be best to do,  given the various dos es of the vaccine that were  used in the initial \nseries and in subsequent ones.  FDA will take this under advisement . \n Dr. Lee emphasized the need to highlight the gap that Dr. Kotton identified and provide some \nguidance to clinicians about how to manage these patients because right now, there are not \noptimal ways to protect those who are immunocompromised who are 5 years of age and \nyounger.  \n \nDr. Das , Moderna,  responded that the primary  series is  25μg  for children, but the booster dose \nis 10 μg for children 6 months to 5 years of age. The 10μg  bivalent booster dose is also the dose \nfor 6 years of age plus.  Dr. Lee noted that the question would be whether to provide the 25μg  \ndose for those  who might be immunocompromised if they are felt to need the additional doses \nversus the one that  is now approved  for those 6 months to 5 years of age.  \n \nDr. Sanchez  expressed appreciation for the flexibility, echoed what had been said about  \nimmunocompromis ed children, and agreed that clarification  was needed.  Given VE in \nimmunocompetent children with the Pfizer and Moderna product s, he would think  that \n28 \n immunocompromised children need further dosing  and would appreciate  not only  further , but \nalso more protec tion in that age group.  In terms of scheduling, the bivalent dosing of 10μg was \nstill confusing to him.  \n \nDr. Twentyman indicated that this would be addressed in the forthcoming Interim Clinical \nConsiderations. CDC is creating a table of precise dosage by both microgram ,  intervals by age, \nand COVID -19 vaccine history  so that providers will be able to look up exactly where their \npatient is sitting on the  table  and provide exactly the dosage indicated from the vial indicated.  To \nspeak to the Moderna issue , the chart indicates that children 6 months to 4 years of age who \nhave not previously received COVID -19 vaccine are recommended to receive 2 doses of \nModerna COVID -19 bivalent vaccine at a dosage of 25  μg from the dark blue cap gray label \nbordered vial at an interval of 4  to 8 weeks  between Dose 1 and Dose 2. That is just one \nexample, but the plan is to provide this guidance  for every age and by history where relevant \namong children ages 6  months through 5  years.  The 10μg  dose  remains  in use for chi ldren with \na history of receipt of  2 doses  of monovalent Moderna COVID -19 vaccines. In other words, that \nrecommendation has not changed from the previous  recommendation, and they can receive the \n10μg  dose from the existing booster dose vial for that age group.  \n \nDr. Marks, FDA, clarified that for the Moderna vaccine, children between the ages of 6  months  \nand 4 years have received 2 doses at 25μg . As in some adult situations,  there can be a  third \ndose given to the immunocompromised at the  same 25μg  dose. A third 25 μg dose of Moderna \nmay be given in that population. I mmunocompromised children who have  not received any  \ndoses could receive up to the 3 doses of Moderna at 25μg  each . That information is included in \nthe Fact Sheet.  \n Dr. Caine  pointed out that the Biden Administration has a B ridge program  for the 30 million \nuninsured adults, and there is an effort to get funding for the vaccine for adults.  One of the \nslides showed that only 9% of Blacks overall have had bivalent COVID -19 vaccine. She asked \nwhether there are any recommendations  and/or funding from ACIP for community -based \norganizations  (CBOs) engaged in outreach to get folks vaccinated. She is concerned about \nthose who are not connected to a medic al home  such as FQHCs  or providers  and about how to \nget them connected to a medical home . Also concerning is that there has been a substantial \nincrease in undocumented immigrants.  \n \nDr. Peacock  indicated that throughout the pandemic, a fairly large amount of funding has been \nprovided to CBOs and various state  and local health departments to focus on this type of work. \nOne of the activities that CDC has  funded is  through the Partnering for Vaccine Equity (P4VE)  \nprogram.  That is COVID -19 supplemental f unding that is  still in place and is  scheduled to go  \nthrough FY24.  CDC is continuing to work with  CBOs, which is a critical need.  Overall, there has \nbeen fairly low uptake of updated vaccine and a lot of work needs to be done to improve \nconfidence and acce ss for these vaccines.  \n \nDr. Hacke ll seconded the comments about addressing pediatric patients whose age group \nchanges, especially during the Moderna primary series because the dose is different.  \nPediatricians  often are asked a lot of  questions by families,  parents, and grandparents . \nAnticipating a possible update in the vaccine in the fall  and thinking about whether the optional \nsecond booster should be received now , there could be an impact on eligibility for a booster in \nthe fall if the composition  of the  vaccine changes . \n  \n29 \n Dr. Oliver emphasized that changes are being made to the recommendation in anticipation that \nthere still may be additional changes this fall. Overall, especially for children,  the additional \ndoses that would be recommended would be for immunocompromised people.  This would be up \nto the clinician , but if there is a de sire and potential benefit, especially based on the level of \nimmunocompromise,  then she would encourage someone to get all available doses.  It is not \nanticipated that getting a dose now would preclude somebody from getting a dose in the fall.  \nReasonably healthy  and perhaps older adults may want to wait until  the fall , which is an option.  \n \nTo clarify some continuing confusion, Dr. Twentyman explained that the transition from the era \nof monovalent mRNA vaccines  to bivalent mRNA vaccines is slightly different for 5- year-olds \nbecause these children were previously recommended to receive either 2 or 3 primary series \ndoses and then  at least 1 bivale nt dose. For 5- year-olds who have started the Moderna series , \nthere are now customized recommendations to make sure that they all receive at least 2 \nvaccine doses in total,  including at least 1 bivalent dose.  Pfizer recipients who have turned age \n5 who received Pfizer or who will receive Pfizer have the very simple recommendation of \nreceiving a single bivalent dose.  \n \nPUBLIC COMMENT  \n \nOverview  \n \nThe floor was opened for public comment on April 19, 2023 at 1:30 PM ET. Given that many \nmore individuals registered to make oral public comments than could be accommodated during \nthis meeting, selection was made randomly via a lottery. Dr. Lee provided a gentle reminder that \nthe ACIP appreciates diverse viewpoints that are respectful in nature and issue- focused. The \ncomments made during the meeting are included in this document. Members of the public also were invited to submit written public comments to ACIP through the Federal eRulemaking Portal \nunder Docket ID CDC- 2023-0028. Visit http://ww w.regulations.gov\n for access to the docket or to \nsubmit comments or read background documents and comments received.  \n \nPublic Comments  \n Donna Treubig  \nLicensed Child Care Provider  \nFamily Traditions Child Care  \n \nThank you. Hello. I am a licensed childcare owner /provider.  I have worked very hard over the \nlast 3 years and continue to work to protect the very young children I care for , including my  \nyoung grandchildren , from this virus. I have no conflicts.  I'm also a proud  member of Protect \nTheir Future, a non -profit grassroots advocacy organization made  up of parents, doctors , and \nscientists d edicated to ensuring that children are prioritized regarding the development  of \nvaccines. While I am a member, the following comment s are my opinions.  Our children need  \nyour commitment to the early approval of the next round of fall vaccines before school starts in \nAugust. We need all children, including children under 5, to be vaccinated and have immunity  \nbefore starting school and daycare this fall.  Please simplify the process. Families across the  \ncountry are actively looking to vaccinate their young children, but pharmacies will not administer  \nthem and pediatric offices cannot manage a large stock of vials.  All vaccine trials and nex t \ngeneration solutions should include all age groups simultaneously.  We know that the vaccines \nare safe and effective. We also know  from the data that children  under 1 are at a higher risk for  \nCOVID  complications. Babies cannot wear a mask to protect themselves.  Even based on \n30 \n today ’s discussion , please do not continue to leave them behind.  It would be beneficial for those \nwho haven't been infected, pregnant women, people with high BMI, and others to have access \nto another bivalent booster before the late summer spike.  There shouldn't be an age range  or \nimmunocompromised requirement  to get a second bivalent booster today. It is too early to move  \nto a once- a-year flu shot -type schedule for COVID . COVID  is still mutating.  The vaccine \nmanufacturers need to be ready and free to produce a variant specific booster  that is quickly \navailable to all age groups. Thank you very much.  \n \nMs. Crescent Martin  \nPregnant Person  \n \nGood afternoon and thank you for the chance  to comment today.  I urge the ACIP and CDC , in \ncoordination with colleagues at FDA as needed,  to immediately grant pregnant people \npermissive  access to an additional COVID  booster based on their pregnancy status. Recently , \nthe WHO updated its recommendations  to include pregnant people as a high priority group and \nto recommend that pregnant people receive an additional  booster dose if their last dose was \nmore than 6  months ago. I was heartened to hear Dr. Sara Oliver state at the February ACIP \nmeeting that a deeper dive into the emerging data on vaccination among pregnant individuals,  \nwith a view towards assessing what data is needed to make recommendations for that  \npopulation, is  among CDC ’s top priorities for upcoming meetings.  But I'm here to remind you \nthat people who are currently pregnant do not have the luxury of waiting for full consideration of \nall of the emerging data.  I received a bivalent booster as soon as I could get an appointment in \nSeptember —more than 7 months ago.  I'm currently in my third trimester of pregnancy  and I \nrecently received a Tdap  booster as recommended to protect my infant against whooping \ncough.  However , under current restrictive US authorizations, I'm not eligible to receive an \nadditional COVID  booster  to maximize the mate rnal antibodies I could be passing on to my \ninfant. These antibodies could help reduce her risk  of serious COVID  complications before she \nis eligible for her own vaccination. For context , this is my second pandemic pregnancy.  My first \npandemic baby was bor n in Summer 2020, a truly scary time to be pregnant , before any \nvaccines were available.  My family tried hard to shield my son from getting COVID  until after he \nwas finally eligible  to be vaccinated in June 2022. In large part , our concerns were about the \nunknown long- term consequences of infection with a novel pathogen , especially with a naïve \nimmune system. In 2023 , we're now fortunate to have the tools of vaccination and so it should \nbe much easier to protect this pandemic baby. However , the current move to an annual  \nvaccination schedule does not have enough flexibility to optimally protect the vulnerable groups  \nof pregnant people and infants under 6  months. As we wait for sufficient evidence to support an \naffirmative policy recommendation that a COVID  booster is absolutely necessary in each  \npregnancy, we do have very strong safety data.  The currently available evidence suggests that \nthe known and potential benefits of an additional booster are likely much higher  than the known \nand potential risks. It woul d be a reasonable choice under a shared clinical decision- making \nmodel for a pregnant person to choose an additional booster dose during pregnancy. CDC and \nFDA policy should not stand in the way of that decision, but instead should ensure that pregnant \npeople have authorized access to additional booster dose if they wish to receive one.  This, of \ncourse,  is in addition to continuing to promote and provide access to vaccination for the many , \nmany pregnant people who are not otherwise up- to-date. Thank you for your consideration and I \nlook forward to hearing your discussion this afternoon.  \n  \n31 \n Dr. Jonathan Vi gh \nProject Scientist  \nNational Center for Atmospheric Research  \n \nThank you so much, Dr. Lee and ACIP members. Thank you for the opportunity to provide input \non this very important subject. I'm a Project Scientist at the National Center for Atmospheric \nResearch in Boulder, Colorado. I'm also a wildfire survivor. My family lost their home in the \nMarshall Fire. My 2 children attend elementary school here in Colorado and there has been a \nfrightful amount of illness at their school this year, inc luding COVID, RSV, flu, and strep.  \nAlthough no one in my family has tested positive for COVID so far, my son has been sick for \nweeks and we worry he could be suffering from post -viral syndrome. I've learned that resilience \nis vital, and that health cannot be taken for granted. I had Moderna for my first 3 vaccinations. \nAfter my second shot, I experienced a strong reaction which included fever, malaise, heart \npalpations, and chest pain. My first booster was only somewhat better. It was miserable to have \nto miss a day of work each time I got vaccinated. Last fall, I was due for my second booster, so I \ndecided to try Novavax. The difference was night and day. The only side effects I experienced \nwere a sore arm, a slight tingle in my scalp, and feeling a little tired in the evening. I was able to \nwork the next day and for me,  Novavax was a game changer. From everything I've heard, I \nunderstand that Novavax's monovalent vaccine has effectiveness on par with the bivalent \nvaccines. Recent real -world data shows that the mRNA protection starts strong and begins \nfading as early as 4 months. In contrast, Novavax offers durable,  lasting protection and \nexcellent protection against severe disease with fewer side effects. Also, many people suffering \nlong- COVID have reported that Novavax improved their symptoms. The weight of evidence that \nwe have in hand shows that Novavax is an effective and safe vaccine. Therefore, it is  \ninexplicable why the current guidelines make it nearly impossible for Americans to get Novavax as a seco nd booster. I have not seen any scientific justification that supports this restriction. I'm  \nasking for 4 changes to vaccine immunization practice today: 1) Please allow all age groups to get vaccinated more than once per year , if desired; 2) Please speed up the timeline for kids \nunder 12 to be able to get Novavax. I would like my kids to get it; 3) allow kids to get their \nbooster a full month before the school year starts; and 4) Please, please change the guidelines \nto allow people to get Novavax without r egard to their previous vaccination history. We won't \nachieve full vaccine equity until all Americans have the freedom to choose the vaccine that is \nbest for them. Once we achieve this, I believe that we will see improved uptake of boosters. \nThis will move  the needle toward stopping transmission and finally ending this pandemic. Thank \nyou very much.  \n \nMs. Gwendolyn Kull  \nAttorney & Contributing Author  \nBrownstone Institute  \n \nThank you. M y name is Gwendolyn Kull, I'm an A ttorney and a C ontributing Author for  \nBrownstone Institute.  I'm here today to speak about the policy requiring COVID -19 vaccination \nfor foreign travelers to the United States.  And for those of you who might not be aware, the CDC \nhas an A mended Order mandating that all travelers , non-citizen, non -immigrants , to the United \nStates be vaccinated before boarding an airplane. If this policy were truly for preventing disease,  shouldn't we instead mandate testing? This policy has failed at its purpose and is \ncosting thousands, precious time with their family members , and the US economy billions in \nrevenue. As of August 19, 2022 , the CDC public policies should not  differentiate by a person’ s \nvaccination status  because of breakthrough infections. Yet this policy continues, leaving those \nof us harmed by it  to question why.  Vindictive punishment for the exercise of medical autonomy \nor religion? The CDC has a duty to the American public  and the US Constitution to rescind the \n32 \n policy regardless of President Biden's proclamation because it is unconstitutional. I t is an  \nunlawful delegation under T itle 3 since Director Walensky was not appointed through Senate \nconfirmation. It is not rationally related to the purpose of disease prevention since vaccines do \nnot prevent the disease, a nd it further causes families to be separated.  It oversteps authority  \nvested by Congress under the Administrative Procedures Act by creating additional \nrequirements for entry  into the United States than are actually legislated under T itle 8, Section \n1182a, w hich only requires proof of vac cination against vaccine -preventable diseases prior to \nentry.  Even if the vaccine did prevent disease, the policy is still ineffective because it doesn't \napply to Americans who can travel nearly anywhere in the globe unvaccinated,  free to transmit \nthe disease. In reality, the policy fails  because the vaccines do not prevent disease and it allows \npeople with active COVID  infections to fly  to the US so long as they present proof of  \nvaccination. As a result of this policy , bi-national families have been  kept a part—some for more \nthan 3 years. Unvaccinated visa holders living in the United States have been trapped here for \nfear they will be denied re- entry and lose their jobs or education. Tourists choose non- US \ndestinations.  The vaccine is now also senselessly on the immigration schedule for adults and \nchildren, again violating 1182a and the PREP Act.  Probable reciprocity is not maintained with \nother nations and the US lost nearly $100 billion between lost tourism revenue and the cost of \nenforcement in the last year alone. Stop wasting resources and taxpayer dollars on this moot  \nand unlawful policy that's causing real harm to innocent , healthy people while not preventing \ntransmission.  Resend the amended order implementing P roclamation 10294. T hank you . \n \n  \n33 \n CERTIFICATION  \n \nUpon reviewing the foregoing version of the April 19, 2023 ACIP meeting minutes, Dr. Grace \nLee, ACIP Chair, certified that to the best of her  knowledge, they are accurate and complete.  \nHer original, signed certification is on file with the Management Analysis and Services Office \n(MASO) of CDC.  \n  \n34 \n  \nACIP MEMBERSHIP ROSTER  \n \nCHAIR  \nLEE, Grace M, MD, MPH  \nAssociate Chief Medical Officer for Practice Innovation  \nLucile Packard Children’s Hospital  \nProfessor of Pediatrics, Stanford University School of Medicine  Stanford, CA  \nTerm: 8/4/2021 – 6/30/2023  \n \nEXECUTIVE SECRETARY  \nWHARTON, Melinda, MD, MPH  \nNational Center for Immunization and Respiratory Diseases  \nCenters for Disease Control and Prevention \nAtlanta, GA  \n \nMEMBERS   \nBAHTA, Lynn, RN, MPH, CPH  \nImmunization Program Clinical Consultant  \nInfectious Disease, Epidemiology, Prevention & Control Division  \nMinnesota Department of Health  \nSaint Paul, Minnesota  \nTerm: 7/1/2019 – 6/30/2023   \n  \nCHEN, Wilbur H, MD, MS, FACP, FIDSA  \nProfessor of Medicine  Center for Vaccine Development and Global Health  \nUniversity of Maryland School of Medicine  \nBaltimore, MD  \nTerm: 12/23/2020 – 6/30/2024  \n \nDALEY, Matthew F, MD  \nSenior Investigator   Institute for Health Research, Kaiser Permanente Colorado   \nAssociate Professor of Pediatrics  \nUniversity of Colorado School of Medicine  \nAurora, CO  \nTerm: 1/4/2021 – 6/30/2024  \n  \nKOTTON, Camille Nelson, MD, FIDSA, FAST  \nClinical Director, Transplant and Immunocompromised Host Infectious Diseases  \nInfectious Diseases Division, Massachusetts General Hospital   \nAssociate Professor of Medicine, Harvard Medical School  \nBoston, MA  \nTerm: 12/23/2020 – 6/30/2024  \n \n  \n35 \n LOEHR, Jamie, MD, FAAFP  \nOwner, Cayuga Family Medicine  \nIthaca, New York  \nTerm: 7/26/2021 –  6/30/2025 \n  \nLONG, Sarah S, MD  \nProfessor of Pediatrics  \nDrexel University College of Medicine  \nSection of Infectious Diseases  \nSt. Christopher’s Hospital for Children  \nPhiladelphia, Pennsylvania  \nTerm: 12/24/2020 – 6/30/2024  \n  \nMCNALLY, Veronica V, JD  \nPresident and CEO Franny \nStrong Foundation  \nWest Bloomfield, Michigan  \nTerm: 10/31/2018 – 6/30/2022  \n \nPOEHLING, Katherine A, MD, MPH  \nProfessor of Pediatrics and Epidemiology and Prevention  \nDirector, Pediatric Population Health  \nDepartment of Pediatrics  \nWake Forest School of Medicine  \nWinston- Salem, NC  \nTerm: 7/1/2019 –  6/30/2023  \n  \nSÁNCHEZ, Pablo J, MD  \nProfessor of Pediatrics  \nThe Ohio State University –  Nationwide Children’s Hospital  \nDivisions of Neonatal -Perinatal Medicine and Pediatric Infectious Diseases  \nDirector, Clinical & Translational Research (Neonatology)  \nCenter for Perinatal Research  \nThe R esearch Institute at Nationwide Children's Hospital Columbus, Ohio   \nTerm: 7/1/2019 –  6/30/2023  \n \nTALBOT, Helen Keipp, MD  \nAssociate Professor of Medicine  Vanderbilt University  \nNashville, TN  \nTerm: 10/29/2018 –  6/30/2022  \n  \n36 \n  \nEX OFFICIO MEMBERS  \n  \nCenters for Medicare and Medicaid Services (CMS)   \nHANCE, Mary Beth  \nSenior Policy Advisor  \nDivision of Quality, Evaluations and Health Outcomes  \nChildren and Adults Health Programs Group  \nCenter for Medicaid, CHIP and Survey & Certification Centers \nfor Medicare and Medicaid Services  \nBaltimore, MD  \n \nFood and Drug Administration (FDA)    \nFINK, Doran, MD, PhD  \nDeputy Director, Clinical, Division of Vaccines and Related Products Applications  \nOffice of Vaccines Research and Review  \nCenter for Biologics Evaluation and Research  \nFood and Drug Administration  \nSilver Spring, MD  \n  \nHealth Resources and Services Administration (HRSA)  \nRUBIN, Mary, MD  Chief Medical Officer  \nDivision of Injury Compensation Programs  \nRockville, MD  \n \nIndian Health Service (IHS)  \nCLARK, Matthew, MD, FAAP, FACP \nPhysician \nChair, IHS National Pharmacy & Therapeutics Committee  \nDurango, CO  \n  \nOffice of Infectious Disease and HIV/AIDS Policy (OIDP)  \nKIM, David, MD, MA  \nDirector, Division of Vaccines, OIDP  \nOffice of the Assistant Secretary for Health  \nDepartment of Health and Human Services  \nWashington, DC  \n  \nNational Institutes of Health (NIH)  \nBEIGEL, John, MD  \nAssociate Director for Clinical Research  \nDivision of Microbiology and Infectious Diseases  \nNational Institute of Allergy and Infectious Diseases (NIAID)  \nBethesda, MD  \n  \n37 \n LIAISON REPRESENTATIVES  \n \nAmerican Academy of Family Physicians (AAFP)  \nROCKWELL, Pamela G, DO  \nAssociate Professor, Department of Family Medicine, University of Michigan Medical School  \nMedical Director, Dominos Farms Family Medicine  \nAnn Arbor, MI  \n  \nAmerican Academy of Pediatrics (AAP)  \nMALDONADO, Yvonne, MD  \nSenior Associate Dean for Faculty Development and Diversity  \nProfessor of Pediatrics and Health Research and Policy  Chief, Division of Pediatric Infectious Diseases  \nStanford University School of Medicine  \nStanford, CA  \n \nAmerican Academy of Pediatrics (AAP)  \nRed Book Editor  \nKIMBERLIN, David, MD  \nProfessor of Pediatrics  \nDivision of Pediatric Infectious Diseases  \nThe University of Alabama at Birmingham School of Medicine \n Birmingham, AL  \n  \nAmerican Academy of Physician Assistants (AAPA)  \nLÉGER, Marie -Michèle, MPH, PA -C  \nSenior Director, Clinical and Health Affairs  \nAmerican Academy of Physician Assistants  \nAlexandria, VA  \nAmerican College Health Association (ACHA)  \nCHAI, Thevy S., MD   \nDirector of Medical Services  \nCampus Health Services  \nUniversity of North Carolina at Chapel Hill Chapel Hill, \nNC   \n  \nAmerican College Health Association (ACHA) (alternate)  \nMCMULLEN, Sharon, RN, MPH, FACHA  \nAssistant Vice President of Student & Campus Life for Health and Wellbeing Cornell Health  \nIthaca, NY  \n  \nAmerican College of Nurse Midwives (ACNM)  \nHAYES, Carol E., CNM, MN, MPH  \nLead Clinician  \nClinical Quality Compliance and Management \nPlanned Parenthood Southeast  Atlanta, GA  \n  \n  \n38 \n American College of  Nurse Midwives (ACNM) (alternate)  \nMEHARRY, Pamela M., PHD, CNM  \nMidwifery Educator, Human Resources for Health  \nIn partnership with University of Rwanda and University of Illinois, Chicago  \n  \nAmerican College of Obstetricians and Gynecologists (ACOG)  ECKERT,  Linda O, MD, FACOG  \nProfessor, Department of Obstetrics & Gynecology  \nAdjunct Professor, Department of Global Health  \nUniversity of Washington  \nSeattle, WA   \n  \nAmerican College of Physicians (ACP)  \nGOLDMAN, Jason M , MD, FACP  \nAffiliate Assistant Professor of Clinical Biomedical Science, Florida Atlantic University, Boca \nRaton, Florida  \nPrivate Practice  \nCoral Springs, FL  \n \nAmerican Geriatrics Society (AGS)  \nSCHMADER, Kenneth, MD  \nProfessor of Medicine- Geriatrics Geriatrics \nDivision Chief  Duke University and Durham VA Medical Centers  \nDurham, NC  \n  \nAmerica’s Health Insurance Plans (AHIP)  \nGLUCKMAN, Robert A, MD, MACP  \nChief Medical Officer, Providence Health Plans  \nBeaverton, OR  \n  \nAmerican Immunization Registry Association (AIRA)  \nCOYLE, Rebecca, MSEd  \nExecutive Director, AIRA  \nWashington, DC  \n  \nAmerican Medical Association (AMA)  \nFRYHOFER, Sandra Adamson, MD  \nAdjunct As sociate Professor of Medicine Emory \nUniversity School of Medicine  Atlanta, GA  \n  \nAmerican Nurses Association (ANA)  \nRITTLE, Charles (Chad), DNP, MPH, RN Assistant \nProfessor, Nursing Faculty  \nChatham University, School of Health Sciences  \nPittsburgh, PA  \n  \n  \n39 \n American Osteopathic Association (AOA)  \nGROGG, Stanley E, DO  \nAssociate Dean/Professor of Pediatrics  \nOklahoma Sta te University -Center for Health Sciences  \nTulsa, OK  \n \nAmerican Pharmacists Association (APhA)  \nHOGUE, Michael D., PharmD, FAPhA, FNAP  \nDean and Professor of Loma Linda University School of Pharmacy  \nDirector, Center for Interprofessional Education & Practice \nLoma Linda, CA  \n Association of Immunization Managers (AIM)  \nHOWELL, Molly, MPH   Immunization Program Manager   \nNorth Dakota Department of Health  \nBismarck, ND  \n \nAssociation for Prevention Teaching and Research (APTR)  \nZIMMERMAN, Richard, MD, MPH  \nProfessor  \nUniversity of Pittsburgh School of Medicine \nDepartment of Family Medicine and Clinical Epidemiology  \nPittsburgh, PA  \n  \nAssociation of State and Territorial Health Officials (ASTHO)  \nSHAH, Nirav D, MD, JD  \nDirector   \nMaine Center for Disease Control and Prevention   \nAugusta, ME  \n \nBiotechnology Industry Organization (BIO)  \nARTHUR, Phyllis A, MBA  \nSenior Director, Vaccines, Immunotherapeutics and Diagnostics Policy  \nWashington, DC   \n  \nCouncil of State and Territorial Epidemiologists (CSTE)   \nHAHN, Christine, MD  \nState Epidemiologist  \nOffice of Epidemiology, Food Protection and Immunization Idaho \nDepartment of Health and Welfare  \nBoise, ID  \n  \nCouncil of State and Territorial Epidemiologists (CSTE) (alternate)  \nLETT, Susan, MD, MPH  \nMedical Director, Immunization Program  \nDivision of Epidemiology and Immunization  \nMassachusetts Department of Public Health  \nBoston, MA  \n \n40 \n Canadian National Advisory Committee on Immunization (NACI)  \nDEEKS, Shelley, MD, MHSc, FRCPC, FAFPHM  \nDeputy Chief Medical Officer of Health, Department of Health and Wellness, Nova Scotia  \nAssociate Professor, Dalla Lana School of Public Health, University of Toronto  \nChair, National Advisory Committee on Immunization \nHalifax, Nova Scotia  \n \nInfectious Diseases Society of America (IDSA)   \nBAKER, Carol J., MD  \nProfessor of Pediat rics  \nMolecular Virology and Microbiology  \nBaylor College of Medicine  \nHouston, TX  \n \nInternational Society for Travel Medicine (ISTM)  \nBARNETT, Elizabeth D, MD Professor of \nPediatrics  \nBoston University School of Medicine  \nBoston, MA  \n  \nNational Association of County and City Health Officials (NACCHO)  \nZAHN, Matthew, MD  \nMedical Director, Epidemiology  \nOrange County Health Care Agency  \nSanta Ana, CA  \n     \nNational Association of County and City Health Officials (NACCHO) (alternate)  \nDUCHIN, Jeffrey, MD  \nHealth Officer and Chief, Communicable Disease \nEpidemiology and Immunization Section   \nPublic Health -  Seattle and King County  \nProfessor in Medicine   \nDivis ion of Allergy and Infectious Diseases  \nUniversity of Washington School of Medicine and School of Public Health  \nSeattle, WA  \n  \nNational Association of Pediatric Nurse Practitioners (NAPNAP)  \nSTINCHFIELD, Patricia A, RN, MS, CPNP  \nDirector  \nInfectious Disease/Immunology/Infection Control  \nChildren's Hospitals and Clinics of Minnesota  \nSt. Paul, MN  \n  \nNational Foundation for Infectious Diseases (NFID)  \nSCHAFFNER, William, MD  Chairman, Department  of Preventive Medicine  \nVanderbilt University School of Medicine  \nNashville, TN  \n  \n  \n41 \n National Foundation for Infectious Diseases (NFID) (alternate)  \nDALTON, Marla, PE, CAE  \nExecutive Director & CEO  \nNational Foundation for Infectious Diseases (NFID)  \nBethesda, MD  \n \nNational Medical Association (NMA)  \nWHITLEY -WILLIAMS, Patricia, MD Professor a nd Chair  \nUniversity of Medicine and Dentistry of New Jersey Robert Wood \nJohnson Medical School   \nNew Brunswick, NJ  \n \nPediatric Infectious Diseases Society (PIDS)  \nO’LEARY, Sean, MD, MPH  \nAssociate Professor of Pediatrics  \nPediatric Infectious Diseases  \nGeneral Academic Pediatrics  \nChildren’s Hospital Colorado  \nUniversity of Colorado School of Medicine  \n  \nPediatric Infectious Diseases Society (PIDS) (alternate)   \nSAW YER, Mark H, MD  \nProfessor of Clinical Pediatrics  \nUniversity of California, San Diego School of Medicine  \nSan Diego, CA  \n     \nPharmaceutical Research and Manufacturers of America (PhRMA)  \nROBERTSON, Corey, MD, MPH   \nSenior Director, US Medical, Sanofi Pasteur   \nSwiftwater, PA  \n  \nSociety for Adolescent Health and Medicine (SAHM)  MIDDLEMAN, Amy B, MD, MSEd, MPH  \nProfessor of Pediatrics  \nChief, Section of Adolescent Medicine  \nUniversity of Oklahoma Health Sciences Cente r \nOklahoma City, OK  \n  \nSociety for Healthcare Epidemiology of America (SHEA)  \nDREES, Marci, MD, MS  \nChief Infection Prevention Officer & Hospital Epidemiologist  \nChristianaCare  \nWilmington, DE  \nAssociate Professor of Medicine  \nSidney Kimmel Medical College at Thomas Jefferson University Philadelphia, PA  \n \n  \n42 \n  \nACRONYMS USED IN THIS DOCUMENT   \n \nAcronym  Extension  \nAAFP  American Academy of Family Physicians  \nAAP American Academy of Pediatrics  \nACHA  American College Health Association  \nACIP  Advisory Committee on Immunization Practices  \nACOG  American College of Obstetricians and Gynecologists  \nACP American College of Physicians  \nAE Adverse Event  \nAHIP  America’s Health Insurance Plans  \nAI/AN  American Indian/Alaskan Native  \nAIM Association of Immunization Managers  \nAIRA  American Immunization Registry Association  \nAMA  American Medical Association  \nAOA  American Osteopathic Association  \nAPhA  American Pharmacists Association  \nAR Adverse Reaction  \nARI Acute Respiratory Illness  \nASTHO  Association of State and Territorial Health Officers  \nBEST  Biologics Effectiveness and Safety System  \nBLA Biologics License Application  \nCBO  Community -Based Organizations  \nCDC  Centers for Disease Control and Prevention  \nCHIP  Children’s Health Insurance Program  \nCISA  Clinical Immunization Safety Assessment  \nCMS  Center for Medicare and Medicaid Services  \nCOI Conflict of Interest  \nCSTE  Council of State and Territorial Epidemiologists  \nDFO  Designated Federal Official  \nDoD Department of Defense  \nDSMB  Data Safety Monitoring Board  \nDUA  Data Use Agreement  \nDVA Department of Veterans Affairs  \nED Emergency Department  \nEHR  Electronic Health Record  \nET Eastern Time  \nEtR Evidence to Recommendation  \nEUA Emergency Use Authorization  \nFDA Food and Drug Administration  \nFQHC  Federally Qualified Health Center  \nGBS  Guillain -Barré Syndrome  \nGMR  Geometric Mean Ratio  \nGMT  Geometric Mean Titers  \nGRADE  Grading of Recommendation Assessment, Development and Evaluation  \nHCP  Healthcare Personnel / Providers  \nHHS  (Department of) Health and Human Services  \n43 \n IDSA  Infectious Disease Society of America  \nIHS  Indian Health Service  \nIIS Immunization Information System  \nMMWR  Morbidity and Mortality Weekly Report  \nNACCHO  National Association of County and City Health Officials  \nNACI  National Advisory Committee on Immunization Canada  \nNAPNAP  National Association of Pediatric Nurse Practitioners  \nNCEZID  National Center for Emerging and Zoonotic Infectious Diseases  \nNCHS  National Center of Health Statistics  \nNCIRD  National Center for Immunization and Respiratory Diseases  \nNFID  National Foundation for Infectious Diseases  \nNIAID  National Institute of Allergy and Infectious Diseases  \nNIH National Institutes of Health  \nNMA  National Medical Association  \nNP Nasopharyngeal  \nNVAC  National Vaccine Advisory Committee  \nNVPO  National Vaccine Program Office  \nNVSN  New Vaccine Surveillance Network  \nOIDP  Office of Infectious Disease and HIV/AIDS Policy  \nPCP Primary Care Provider/Practitioner  \nPCR  Polymerase Chain Reaction  \nPHAC  Public Health Agency Canada  \nPHE Public Health Emergency  \nPICO  Population, Intervention, Comparison, Outcomes  \nPIDS  Pediatric Infectious Disease Society  \nRCA  Rapid Cycle Analysis  \nRCT Randomized Controlled Trial  \nSAE Serious Adverse Event  \nSAHM  Society for Adolescent Health and Medicine  \nSHEA  Society for Healthcare Epidemiology of America  \nSME  Subject Matter Expert  \nSVI Social Vulnerability Index  \nUK  United Kingdom  \nUS United States  \nUSG  United States Government  \nVAERS  Vaccine Adverse Event Reporting System  \nVE Vaccine Efficacy  \nVE Vaccine Effectiveness  \nVFA Vaccines for Adults  \nVFC Vaccines For Children  \nVRBPAC Vaccines and Related Biological Products Advisory Committee  \nVSD Vaccine Safety Datalink  \nWG Work Group  \nWHO  World Health Organization", "summary": "MEETING OF THE ADVISORY  COMMITTEE ON IMMUNIZATION  PRACTICES (ACIP)     APRIL 19 , 2023  MEETING SUMMARY     CONTENTS   WEDNESDAY: APRIL 19, 2023 .................................................................................................................... 2   WELCOME AND INTRODUCTIONS  ...................................................................................... 2   Call to Order/Roll Call…", "source_url": "https://www.cdc.gov/acip/meetings/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/minutes/summary-2023-04-19-508.pdf", "doc_date": "2023-04-19", "case": "acip", "sub_case": "minutes", "tags": ["acip", "cdc", "vaccines", "minutes"], "page_count": 43}
{"title": "agenda 2023 02 22 24 508", "content": "Final - February 17, 2023 \nMEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP) \nCenters for Disease Control and Prevention \nAtlanta, Georgia 30329 \nFebruary 22-24, 2023 \nWednesday, February 22, 2023 \n8:00 Welcome & Introductions  Dr. Grace Lee (ACIP, Chair) \nDr. Melinda Wharton (ACIP Executive Secretary, CDC) \n8:30 Mpox Vaccine \nIntroduction Epidemiology of mpox during 2022 outbreak in the United States \nJYNNEOS vaccine safety \nJYNNEOS vaccine effectiveness Mpox vaccine acceptability and uptake from cross-sectional surveys \nInterim clinical considerations \nEtR: Use of JYNNEOS during mpox outbreaks Dr. Pablo Sanchez (ACIP, WG Chair) \nDr. Sascha Ellington (CDC/NCCDPHP) \nDr. Jonathan Duffy (CDC/NCEZID) \nDr. Anna Chard (CDC/NCIRD) Dr. Kevin P. Delaney (CDC/NCHHSTP) \nDr. Rosalind Carter (CDC/NCIRD) \nDr. Agam Rao (CDC/NCEZID) \n11:30 Break \n12:30 Respiratory disease surge, Fall 2022, United States Dr. José R. Romero (CDC, Director NCIRD) \n1:00 Influenza Vaccine \nIntroduction U.S. Influenza activity update Preliminary 2022-23 influenza vaccine effectiveness: CDC networks \nPreliminary 2022-23 influenza vaccine effectiveness: Wisconsin Dr. Keipp Talbot (ACIP, WG Chair) \nDr. Lisa Grohskopf (CDC/NCIRD) Ms. Samantha Olson, Dr. Nathaniel Lewis, Dr. Mark  \nTenforde (CDC/NCIRD) \nDr. Huong McLean, Marshfield Clinic Research Institute \n1:50 Break \n2:00 Public Comment \n2:30 VOTES \nMpox Dr. Agam Rao (CDC/NCEZID) \n2:50 Break \n3:00 Pneumococcal Vaccines \nIntroduction \nEpidemiology of pneumococcal disease among U.S. children Estimating the impact of higher-valency PCVs on pediatric outpatient ARI  \nvisits and antibiotic use \nPCV20 Phase 2/3 study results among children  \nPreliminary EtR (incl. GRADE) for PCV20 use in U.S. children \nWorkgroup considerations Dr. Katherine Poehling (ACIP, WG Chair) Mr. Ryan Gierke (CDC/NCIRD) Ms. Laura King (UC Berkeley) \nDr. Wendy Watson (Pfizer) \nDr. Miwako Kobayashi (CDC/NCIRD) Dr. Miwako Kobayashi (CDC/NCIRD) \n5:00 Adjourn \nThursday, February 23, 2023 \n8:00 Welcome & Introductions  Dr. Grace Lee (ACIP, Chair) \nDr. Melinda Wharton (ACIP Executive Secretary, CDC) \n8:10 Agency Updates  \nCDC, CMS, FDA, HRSA, IHS, OIDP, NIH \n8:30 Meningococcal Vaccines  \nIntroduction \nEpidemiology of meningococcal disease in the United States \nPfizer pentavalent meningococcal vaccine \nWorkgroup considerations Dr. Kathy Poehling (ACIP, WG Chair) Ms. Amy Rubis (CDC/NCIRD) \nDr. Jason Maguire (Pfizer) \nDr. Sam Crowe (CDC/NCIRD) \n9:30 Polio Vaccine \nIntroduction Dr. Oliver Brooks (ACIP, WG Chair) Dr. Sarah Kidd (CDC/NCIRD) \nRecommendations for Adult Polio Vaccination \n10:00 Break \n \n Final - February 17, 2023 \n10:20 RSV Vaccines - Pediatric/Maternal \nIntroduction \nCost effectiveness analysis for nirsevimab – CDC model Cost effectiveness analysis for nirsevimab – Comparison to manufacturer  \nmodel \nEvidence to Recommendations framework for nirsevimab \nClinical considerations for nirsevimab Safety and Efficacy of RSV Bivalent PreF Maternal Vaccine Workgroup considerations Dr. Sarah Long (ACIP, WG Chair) Dr. David Hutton (University of Michigan) Dr. Ismael Ortega Sanchez (CDC/NCIRD) \nDr. Jefferson Jones (CDC/NCIRD) \nDr. Jefferson Jones (CDC/NCIRD) Dr. Iona Munjal (Pfizer) Dr. Katherine Fleming-Dutra (CDC/NCIRD) \n12:20 Break \n1:20 RSV Vaccines - Adult \nIntroduction Cost effectiveness of the GSK and Pfizer vaccines (main CDC model) \nComparison of cost effectiveness results of the main CDC model and each  \nmanufacturer model (GSK & Pfizer) \nEtR (incl. GRADE) for 2 vaccines (GSK & Pfizer) \nVaccine policy questions (GSK & Pfizer) Dr. Camille Kotton (ACIP, WG Chair) Dr. David Hutton (University of Michigan) \nDr. Ismael Ortega Sanchez (CDC/NCIRD) \nDr. Michael Melgar (CDC/NCIRD) \nDr. Michael Melgar (CDC/NCIRD) \n3:05 Break \n3:25 Chikungunya Vaccine \nIntroduction Global epidemiology of chikungunya Chikungunya in U.S. travelers Persistent arthralgia following chikungunya Workgroup considerations Dr. Beth Bell (ACIP, WG Chair)  \nDr. Susan Hills (CDC/NCEZID) Ms. Nicole Lindsey (CDC/NCEZID) Ms. Nicole Lindsey (CDC/NCEZID) Ms. Nicole Lindsey (CDC/NCEZID) \n4:25 Dengue Vaccines  \nIntroduction Takeda dengue vaccine (TAK-003) safety and efficacy Workgroup considerations Dr. Wilbur Chen (ACIP, WG Chair) Dr. Shibidas Biswal  (Takeda) Dr. Gabriela Paz-Bailey (CDC/NCEZID) \n5:10 Varicella \nPublic health impact of 25 years of varicella vaccination in the United States Dr. Mona Marin (CDC/NCIRD) \n5:30 Adjorn \nFriday, February 24, 2023 \n8:00 Welcome & Introductions Dr. Grace Lee (ACIP, Chair) \nDr. Melinda Wharton (ACIP Executive Secretary, CDC) \n8:10 COVID-19 Vaccines \nIntroduction Dr. Matthew Daley (ACIP, WG Chair) \nCOVID-19 vaccine safety updates: CDC Dr. Tom Shimabukuro (CDC/NCEZID) \nCOVID-19 vaccine safety updates: FDA Dr. Richard Forshee (FDA) \nVaST summary Dr. Keipp Talbot (ACIP, VaST Co-Chair) \nWG interpretation and summary Dr. Evelyn Twentyman (CDC/NCIRD) \n9:30 Break \n9:45 Updates on COVID-19 hospitalizations: COVID-NET Dr. Chris Taylor (CDC/NCIRD) \nUpdates to COVID-19 vaccine effectiveness in the United States Dr. Amadea Britton (CDC/NCIRD) \nConsiderations for transitioning to bivalent primary series Dr. Sara Oliver (CDC/NCIRD) \n11:30 Break \n11:45 Benefit/risk for COVID-19 vaccines Dr. Megan Wallace (CDC/NCIRD) \nCOVID-19 vaccines: future directions Dr. Sara Oliver (CDC/NCIRD) \n1:45 Adjorn \n \n \n Final - February 17, 2023 \nAcronyms \nARI Acute respiratory illness \nCDC Centers for Disease Control and Prevention \nCMS Centers for Medicare and Medicaid Services \nCOVID-19 Coronavirus disease 2019 \nEtR Evidence to Recommendations Framework \nFDA Food and Drug Administration \nGRADE Grading of Recommendations Assessment, Development and Evaluation \nHRSA Health Resources and Services Administration \nIHS Indian Health Service \nNCHHSTP National Center for HIV, Hepatitis, STD and TB Prevention [of CDC/OID] \nNCIRD National Center for Immunization & Respiratory Diseases [of CDC/OID] \nNCEZID National Center for Emerging and Zoonotic Diseases [of CDC/OID] \nNIAID National Institute of Allergy and Infectious Diseases \nOIDP Office of Infectious Disease and HIV/AIDS Policy \nPCV20 20-valent pneumococcal conjugate vaccine \nSARS-CoV-2 Severe Acute Respiratory Syndrome Coronavirus 2 \nVaST COVID-19 Vaccine Safety Technical Work Group \nWG Work Group \nWHO World Health Organization \nVE Vaccine Effectiveness", "summary": "Final - February 17, 2023  MEETING OF THE ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES (ACIP)  Centers for Disease Control and Prevention  Atlanta, Georgia 30329  February 22-24, 2023  Wednesday, February 22, 2023  8:00 Welcome & Introductions  Dr. Grace Lee (ACIP, Chair)  Dr. Melinda Wharton (ACIP Executive Secretary, CDC)  8:30 Mpox Vaccine  Introduction Epidemiology of mpox during 2022 outbreak in the United States  JYNNEOS vaccine safety  JYNNEOS vaccine effectiveness Mpox vaccine…", "source_url": "https://www.cdc.gov/acip/meetings/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/agendas/agenda-2023-02-22-24-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "agendas", "tags": ["acip", "cdc", "vaccines", "agendas"], "page_count": 3}
{"title": "summary 2023 02 23 24 508", "content": "MEETING OF THE ADVISORY \nCOMMITTEE ON IMMUNIZATION \nPRACTICES (ACIP) \nFEBRUARY 22 -24, 2023 \nMEETING SUMMARY \nCONTENTS  \nWEDNESDAY: FEBRUARY 22, 2023 .......................................................................................................... 5 \nWELCOME AND INTRODUCTIONS ...................................................................................... 5 \nCall to Order/Roll Call ......................................................................................................... 5 \nAnnouncements .................................................................................................................. 5 \nMPOX VACCINE .................................................................................................................... 6 \nOpening Remarks ............................................................................................................... 6 \nSession Introduction ........................................................................................................... 6 \nEpidemiology of Mpox During the Current 2022 Outbreak in the United States ................... 8 \nJYNNEOS Vaccine Effectiveness ......................................................................................11 \nJYNNEOS Vaccine Safety ................................................................................................. 13 \nMpox Vaccine Acceptability and Uptake from Cross -Sectional Surveys .............................17 \nInterim Clinical Considerations ...........................................................................................20 \nEtR: Use of JYNNEOS During Mpox Outbreaks ................................................................. 22 \nACIP Discussion Points, Observations, Suggestions on Mpox Vaccine .............................27 \nVote: Mpox Vaccine ...........................................................................................................31 \nRESPIRATORY DISEASE SURGE, FALL 2022, UNITED STATES ......................................31 \nDiscussion Points ...............................................................................................................33 \nINFLUENZA VACCINE ..........................................................................................................35 \nIntroduction ........................................................................................................................35 \nUS Influenza Activity Update ..............................................................................................35 \nPreliminary 2022 -2023 Influenza Vaccine Effectiveness: CDC Networks ...........................36 \nPreliminary 2022 -2023 Influenza Vaccine Effectiveness: Wisconsin ..................................38 \nUpdate on Published Estimates of LAIV4 Effectiveness: Background ................................39 \nACIP Discussion Points, Observations, Suggestions on Influenza Vaccine ........................40 \n \n   \n  \n  \n   \n  \n   \n   \n  \n  \n    \n  \n   \n  \n  \n   \n   \n  \n  \n   \n  \n  \n   \n  \n  \n   \n  \n  \n   \n   \n  \n  \n   \n    \n  \n  \n  \n   PNEUMOCOCCAL VACCINES .............................................................................................42 \nIntroduction ........................................................................................................................42 \nEpidemiology of Pneumococcal Disease among US Children ............................................43 \nEstimating the Impact of Higher -Valency PCVs on Pediatric Outpatient ARI Visits and \nAntibiotic Use .....................................................................................................................46 \nPCV20 Phase 2/3 Study Results among Children ..............................................................49 \nPreliminary EtR/GRADE for PCV20 use in US Children .....................................................51 \nPneumococcal Vaccines WG Considerations and Next Steps ...........................................55 \nMerck Comments ...............................................................................................................56 \nACIP Discussion Points, Observations, Suggestions on Pneumococcal Vaccine ...............57 \nPUBLIC COMMENTS ............................................................................................................59 \nTHURSDAY: FEBRUARY 23, 2023 ............................................................................................................ 62 \nAGENCY UPDATES ..............................................................................................................62 \nCenters for Disease Control and Prevention ......................................................................62 \nCenters for Medicare and Medicaid Services .....................................................................63 \nHealth Resources and Services Administration ..................................................................64 \nIndian Health Service .........................................................................................................64 \nNational Institutes of Health ...............................................................................................65 \nOffice of Infectious Disease and HIV/AIDS Policy ..............................................................65 \nMENINGOCOCCAL VACCINES ............................................................................................ 66 \nIntroduction ........................................................................................................................66 \nEpidemiology of Meningococcal Disease in the United States ...........................................66 \nPfizer Pentavalent Meningococcal Vaccine ........................................................................68 \nWorkgroup Considerations ................................................................................................. 71 \nACIP Discussion Points, Observations, Suggestions on Meningococcal Vaccines .............73 \nPOLIO VACCINES ................................................................................................................75 \nIntroduction ........................................................................................................................75 \nRecommendations for Adult Polio Vaccination ................................................................... 75 \nACIP Discussion Points, Observations, Suggestions on Polio Vaccines ............................80 \nRSV VACCINES: PEDIATRIC/MATERNAL ...........................................................................80 \nIntroduction ........................................................................................................................80 \nCost-Effectiveness  Analysis for Nirsevimab: CDC Model ...................................................81 \nCost-Effectiveness  Analysis for Nirsevimab: Comparison to Manufacturer Model ..............85 \nEtR Framework for Nirsevimab ..........................................................................................89 \nClinical Considerations for Nirsevimab ...............................................................................97 \nSafety and Efficacy of RSV Bivalent Prefusion F (PreF) Maternal Vaccine ........................98 \nWorkgroup Considerations ............................................................................................... 103 \n2 \n \n   \n   \n   \n   \n      \n  \n   \n   \n   \n   \n    \n   \n   \n    \n  \n   \n   \n   \n  \n   \n   \n   \n    \n   \n   \n    \n   \n   \n   \n   \n   \n  \n  \n   \n   \n   \n    ........................................................................................................................................ 103 ACIP Discussion Points, Observations, Suggestions on Pediatric/Maternal RSV Vaccines \nRSV VACCINES: ADULT .................................................................................................... 107 \nIntroduction ...................................................................................................................... 107 \nCost-Effectiveness  of the GSK and Pfizer Vaccines: Main CDC Model ............................108 \nComparison of Cost -Effectiveness Results of the Main CDC Model and Each Manufacturer \nModel (GSK & Pfizer) ....................................................................................................... 111 \nEtR/GRADE for 2 Vaccines (GSK & Pfizer) ...................................................................... 115 \nGSK Statement ................................................................................................................ 123 \nPfizer Statement .............................................................................................................. 124 \nACIP Discussion Points, Observations, Suggestions on Adult RSV Vaccines .................. 124 \nCHIKUNGUNYA VACCINE .................................................................................................. 126 \nIntroduction ...................................................................................................................... 126 \nGlobal Epidemiology of Chikungunya ............................................................................... 127 \nChikungunya in US Travelers ........................................................................................... 129 \nPersistent Arthralgia Following Chikungunya ................................................................... 131 \nWorkgroup Considerations ............................................................................................... 134 \nACIP Discussion Points, Observations, Suggestions on Chikungunya Vaccines .............. 134 \nDENGUE VACCINE ............................................................................................................. 135 \nIntroduction ...................................................................................................................... 135 \nTakeda Dengue Vaccine (TAK- 003) Safety and Efficacy ................................................. 136 \nWorkgroup Considerations ............................................................................................... 139 \nACIP Discussion Points, Observations, Suggestions on Dengue Vaccines ...................... 141 \nVARICELLA ......................................................................................................................... 141 \nPublic Health Impact of 25 Years of Varicella Vaccination in the United States ................ 141 \nACIP Discussion Points, Observations, Suggestions on Varicella Vaccines ..................... 144 \nFRIDAY: FEBRUARY 24, 2023 ................................................................................................................ 144 \nCOVID -19 VACCINES ......................................................................................................... 144 \nIntroduction ...................................................................................................................... 144 \nPlan to End the COVID -19 Public Health Emergency (PHE) on May 11, 2023 ................. 145 \nCOVID -19 Vaccine Safety Updates: CDC ........................................................................ 146 \nCOVID -19 Vaccine Safety Updates: FDA ......................................................................... 151 \nVaST Summary ................................................................................................................ 154 \nWG In terpretation and Summary ...................................................................................... 155 \nUpdates on COVID -19 Hospitalizations: COVID -NET ...................................................... 157 \nUpdates to COVID -19 Vaccine Effectiveness in the United States ................................... 159 \nConsiderations for Transitioning to Bivalent Primary Series ............................................. 163 \n3 \n \n    \n    \n    \n    \n   \n   \n   \n \n  NCIRD Director Remarks ................................................................................................. 168 \nBenefit -Risk for COVID- 19 Vaccines ................................................................................ 168 \nCOVID -19 Vaccines: Future Directions ............................................................................ 172 \nACIP Discussion Points, Observations, Suggestions on COVID -19 Vaccines .................. 177 \nCERTIFICATION ....................................................................................................................................... 185 \nACIP MEMBERSHIP ROSTER ................................................................................................................ 186 \nACRONYMS USED IN THIS DOCUMENT ............................................................................................... 195 \n4 \n \n  \n \n  \n \n  \n \n      \n      \n    \n   \n     \n \n    \n     \n \n \n \n      \n      \n \n   \n     \n   \n  \n   \n   \n \n \n \n  \n  \n  \n   \n    \n    \n   \n  \n         \n  WEDNESDAY : FEBRUARY 22,  2023  \nWELCOME AND INTRODUCTIONS \nCall to Order/Roll Call \nDr. Grace Lee (ACIP Chair) called to order and presided over the February 22- 24, 2023 \nAdvisory Committee on Immunization Practices (ACIP ) meeting. Dr. Lee conducted a roll call \neach day, which established that a quorum was present. A list of Members, Ex Officios , and \nLiaison Representatives is included in the appendixes at the end of this summary document. \nThe following conflict s of interest (COIs) were identified : \nDr. Camile Kotton is involved in a clinical trial for Takeda for an investigational antiviral for \ncytomegalovirus (CMV) but is not involved in any of their vaccine projects . \nAnnouncements \nDr. Melinda Wharton (ACIP Executive Secretary, CDC) noted that copies of the slides for the \nmeeting were available on the ACIP website and were made available through a ShareLink ™ \nfile for ACIP Voting, Ex O fficios , and Liaisons Members . The ACIP is, at its heart, a public body. \nEngagement with the public and transparency in all of its processes are vital to the committee’s \nwork. She indicated that there would be 1 oral public comment session during this meet ing, \nwhich was scheduled for 2:00 PM Eastern Time ( ET) on February 22, 2023. To create a fair and \nmore efficient process, individuals interested in making an oral comment were asked to submit a request online in advance of the meeting. Priority is given to these advance requests. If more \npeople make requests than can be accommodated, a blind lottery is conducted to determine who the speakers will be. Speakers selected in the lottery for this meeting were notified in advance of the meeting. Members of the public also may submit written comments via \nhttps://www.regulations.gov using Docket Number ID CDC- 2023-00 07. Information on the \nwritten public comment process, including information on how to mak e a comment, can be \nfound on the ACIP website. \nAs noted in the ACIP Policies and Procedures manual, ACIP members agree to forgo \nparticipation in certain activities related to vaccines during their tenure on the committee. For \ncertain other interests that potentially enhance a member’s expertise while serving on the \ncommittee , CDC may issue limited COI waivers. Members who conduct vaccine clinical trials or \nserve on data safety monitoring board s (DSMB s) may present to the committee on matters \nrelated to those vaccines, but those members are prohibited from participating in committee \nvotes on issues related to those vaccines. Regarding other vaccines of the concerned company, \na member may participate in discussions with the provision that he/she abstains on all votes \nrelated to that company. ACIP members state any COIs at the beginning of each meeting. \n5 \n \n  \n  \n \n \n \n     \n  \n \n  \n  \n   \n  \n  \n \n   \n      \n     \n  \n  \n  \n \n \n \n      \n       \n    \n      \n  \n    \n      \n    \n \n      \n    \n     \n      \n    \n       \n    \n      \n      \n  \n  MPOX VACCINE \nOpening Remarks \nDr. Melinda Wharton (ACIP Executive Secretary, CDC) provided opening remarks for the \nMpox session. She reminded everyone that in November 2021, ACIP unanimously voted in \nfavor of JYNNEOS as an alternative to the other available vaccine for prevention of Mpox in \npersons with certain occupational risk of exposure. During this session, ACIP would be asked to \nvote on an additional use of JYNNEOS vaccine for control of Mpox outbreaks. In 2022, a \nmultinational outbreak of Mpox began with more than 30,000 cases in the United States. In response to this outbreak, J YNNEOS has been successfully used in accordance with \nrecommendations in CDC’s interim clinical considerations, and there has been a dramatic reduction in case counts. Dr. Wharton emphasized that the vote for use in outbreaks would not \nchange CDC’s recommendations for use of JYNNEOS in the current outbreak but represents an \nupdate to ACIP’s recommendations that were voted on in late 2021. It is expected that there will \nbe additional decisions coming to ACIP for a vote in future meetings. The recent outbreak has \nhighlighted the risks that infectious diseases can present to communities, the importance of a \nrobust public health response at the state and local level s, the value of engaged partners and \ncommunities in responding to public health threats, and the impact that a vaccine can have in helping to bring an outbreak under control. \nSession Introduction \nPablo Sanchez MD (The Ohio State University−Nationwide Children’s Hospital, ACIP \nMpox WG Chair ) introduced the Mpox session. He pointed out that from a historical context, \nMpox is a rare, sometimes life -threatening infection that is endemic in parts of West and Central \nAfrica. It is caused by the monkeypox virus, which is an orthopoxvirus. There are 2 clades. \nClade 1 was previously known as the Congo Basin Clade, while Clade 2 was previously known \nas the West African clade. Mpox can spread from infected animals to people and then person-\nto-person from respiratory secretions, skin- to-skin contact with infected body fluids (e.g., fluid \nfrom lesions ), and fomites (e.g., s hared towels, clothing, and bedding). \nIn terms of the timeline of notable human Mpox events , during 1970 to 2021, Mpox was known \nto be endemic in 9 African countries : Cameroon, Central African Republic, Côte d'Ivoire, \nDemocratic Republic of Congo, Gabon, Liberia, Nigeria, Republic of Congo, and Sierra Leone. \nDuring recent years, there has been a re- emergence of human cases after decades of no \nreported cases. The first human case was identified in rural settings in 1970. In 2003, there was \na US outbreak from pet prairie dogs with 47 cases identified. In 2017, there was an outbreak in \nNigeria involving 17 states and 138 cases . In 2018, there were imported cases to the United \nKingdom (UK) and Israel with 3 cases identified. In 2019, there were imported cases to the UK \nand Singapore with 2 cases identified. In 2021, there were imported human cases to the UK and \nthe US with 3 cases identified . A multinational outbreak occurred in 2022. \n6 \n \n   \n  \n    \n     \n   \n      \n \n   \n   \n   \n   \n     \n  \n \n \n \n   \n     \n      \n      \n \n \n    \n     \n       \n    \n     \n  \n  \n \n         \n   \n   Person- to-person spread has been seen . Historical outbreaks in Africa have been associated \nwith close skin -to-skin contact and contact with fomites , with zoonotic exposure causing most \ncases and a few secondary cases among close contact s. In the US, a 20 03 outbreak resulted in \nno secondary cases and no vaccination was offered. In 2021, there were no secondary cases \nand ACAM2000 was offered to some contacts.1 In the most recent outbreak in 2022, there were \nmany secondary cases and over 1 million doses of the JYNNEOS vaccine were administered. \nIn 2021, ACIP voted for the of orthopoxvirus vaccine, JYNNEOS that was licensed in 2019 , for \npre-exposure vaccination of people at occupational risk for orthopoxvirus exposures. The \nJYNNEOS vaccine is a 2-dose series that is administered subcutaneous ly. Recommendations \nwere published in the Morbidity and Mortality Weekly Report ( MMWR ) on June 3, 2022.2 \nCurrently, there is no ACIP recommendation for the use of JYNNEOS during outbreaks. The \ncurrent US national Mpox vaccine strategy is shown in this table: \nThe US strategy for vaccination with JYNNEOS during the current outbreak has been that the \nintradermal route is preferred, but the subcutaneous route can be administered for persons ≥18 \nyears of age or older. The subcutaneous route is recommended for persons <18 years of age . \nThis is a 2-dose series with a second dose administered 1 month after the first dose. \nRegarding the tentative timeline for ACIP discussions and votes, during the February 2023 \nmeeting, the ACIP would be voting on the use of 2-dose JYNNEOS for persons ≥18 years of \nage. In June 2023 , ACIP will be discussing the use of 2-dose JYNNEOS for persons aged <18 \nyears of age and would hear updates about vaccine effectiveness (VE) and safety. In October \n2023, there will be consideration for a longer -term vaccination strategy for the 2-dose \nJYNNEOS vaccine. It is important to note that the current US Mpox vaccination strategy \nremains active , which is t hat populations at high risk should continue to be vaccinated. \n1 ACAM2000 was offered through a CDC Investigational New Drug Protocol that allows for vaccination after mpox exposure. Only \ncontacts with highrisk exposures were offered vaccine; none accepted. \n2 https://www.cdc.gov/mmwr/volumes/71/wr/mm7122e1.htm \n7 \n \n     \n     \n   \n     \n  \n \n   \n  \n \n  \n   \n   \n \n \n   \n \n     \n      \n  \n  \n    \n     \n    \n   \n   \n \n \n  \n       \n    \n  \n   \n  \n       \n  \n \n     \n \n      \n    \n      \n      \n  \n   \n \n \n   \n     \n    \n     \n   This session included updates from the ongoing outbreak in terms of epidemiology , VE, vaccine \nsafety, community engagement, and equity and implementation; discussion about the use of the \n2-dose JYNNEOS subcutaneous ly during Mpox outbreaks with an Evidence- to-\nRecommendations Framework presentation and an ACIP vote. Dr. Sanchez presented the \nfollowing proposed wording for the vote: \nACIP recommends the 2-dose* JYNNEOS vaccine ser ies for persons aged 18 years and \nolder at risk of Mpox during an Mpox outbreak. § \n*Dose 2 administered one month after dose 1 \n§ Public health authorities determine whether there is an mpox outbreak; a single case may be considered an mpox outbreak at the discretion of public health authorities. Other circumstances in which a public health response may be \nindicated include ongoing risk of introduction of mpox into a community due to disease activity in another geographic area. \nEpidemiology of Mpox During the Current 2022 Outbreak in the United States \nSascha Ellington, PhD, MSPH (CDC/NCCDPHP) presented an update on the epidemiology of \nthe current Mpox outbreak on behalf of the E pidemiology Task Force of CDC ’s Mpox Response. \nThe first US case associated with the current Mpox outbreak was identified in Massachusetts in \nMay 2022. Cases initially were associated with travel. Since then, cases have been reported \nfrom all 50 states , DC, and Puerto Rico. More than 30,000 cases have been reported to d ate. \nStates with the most cases including California, New York, Texas, Florida, Georgia, and Illinois \nall reporting more than 1,000 cases. Most cases have occurred in gay, bisexual, and other men \nwho have sex with men (MSM) . Cases have also been reported in men who have not reported \nsex with men, cisgender and transgender women, transgender men, gender diverse people, \nchildren, and teens. \nUS cases peaked in August 2022 and have declined substantially since. Currently, the 7-day \nmoving average is 2 cases per day in the US. As of February 8, 2023, 95% of all cases reported \nhave been amongst cisgender men, 2.9% amongst cisgender women, and a combined 1.7% of \ncases have been among transgender men, transgender women, and gender diverse people. \nThe age of people w ith Mpox ranges from 0, with a few cases reported in neonates , up to 89 \nyears of age. The median age is 34 years. Overall, cases have been reported primarily among \nBlack, Hispanic, and White persons , with nearly a third in each of these groups. At the start of \nthe outbreak, about 45% of cases were among White persons, which decreased over time. \nCases in B lack or African American persons increased and cases among Hispanic or Latino \npersons have remained fairly stable over the period of the outbreak. \nIn terms of clinical characteristics and outcomes among cases reported to date, 53% of cases \nwith available data have been among people living with HIV and 47% of cases have been \namong people who are human immunodeficiency virus (HIV)-negative, though only 30% of \ncases reported had data on HIV status. Among cases with available data, more than half had \nrash reported on the genitals or perianal area, trunk or limbs, head, face, or mouth . About a \nquarter had rash on the palms or soles of the feet. About 7.7% of people with Mpox have been \nhospitalized and 32 Mpox -associated deaths have been reported, representing 0.1% of cases. \nDeaths have occurred primarily in severely immunocompromised persons. \nDuring the current outbreak, Mpox has been spread primarily through sexual or close intimate \ncontact. Other routes of transmission also have been reported, including household \ntransmission through injury with a contaminated sharp instrument in a clinical setting, thr ough \npiercing and tattooing, and perinatal transmission from an infected mother to an infant around \nthe time of delivery. Current evidence suggests that some people can spread Mpox virus to \n8 \n \n     \n  \n     \n  \n \n \n \n \n  \n   \n  \n  \n     \n    \n \n \n     \n  \n  \n    \n      \n   \n    \n  \n \n   \n    \n    \n    \n      \n    \n  \n \n   others 1 to 4 days before they become symptomatic. However, there is no evidence that people \nwho never develop symptoms have spread the virus to others. This table summarizes the \nspecimens in which Mpox has been detected by polymerase chain reaction (PCR) , whether \nreplication- competent  viruses has been detected, and whether each exposure source has been \nassociated with transmission: \nReplication -competent virus has been detected but isolated in skin lesions, oropharyngeal \nswabs, anorectal swabs, semen, urine, and ocular fluid. Mpox has been transmitted from skin-\nto-skin contact, oral contact, and from a contaminated sharp. Transmission via exposure to \nsome sources such as semen can be particularly challenging to assess since exposure typically occurs during close intimate contact that also includes skin- to-skin contact. For this reason, \nmany exposure sources listed in the table have insufficient data to conclude definitively they are \na source of infection. \nAs previously mentioned, 95% of cases of Mpox have been reported amongst cisgender men, \nand cases have occurred primarily among gay, bisexual, and other MSM . Among the cases \nreported in men with data on recent sexual history, 75% reported sexual or close intimate contact with a man in the 3 weeks preceding symptom onset. However, in 25% of cases among \nmen, no recent male- to-male sexual contact was reported. Over time, the percentage of cases \nin men that had recent male- to-male sexual contact has declined from over 80% initially to \nabout 60%, increases have been observed in the missingness of sexual contact data, which \nmay contribute at least partially to this decline. \nA few specific populations have been less affected overall, but the characteristics of these \ncases have contributed to the overall understanding of the epidemiology. Based on dat a from a \npublication that was published earlier this year reporting on cases in cisgender women,\n3 about \n3% of the Mpox cases have been in cisgender women. The m edian age of cases in this group is \n32 years, ranging from 15─89 years . Of the cases among cisgender women, 44% were in \nBlack, non-Hispanic  women ; 25% were in W hite, non- Hispanic women, and 23% were in \nHispanic or Latino women. Of those with available data on HIV status, 8% of cases in cisgender \n3 http://dx.doi.org/10.15585/mmwr.mm7201a2 \n9 \n \n       \n   \n    \n  \n \n   \n   \n  \n    \n   \n     \n   \n    \n    \n  \n  \n    \n      \n    \n  \n  \n \n    \n     \n   \n   \n   \n      \n   \n  \n    \n \n \n     \n     \n      \n   \n   \n    \n    \n  \n \n      \n    \n     \n     \n       \n    \n \n   \n   women were HIV -positive, and 92% were HIV negative. While the data were available for only \n22% of cases among cisgender women, this is markedly lower than the percent of total cases \nthat were HIV -positive at 53% and 71% of cases among cisgender women reported a recent \nsexual or close intimate part ner. \nThe same publication also reported on cases in pregnant people. From May 11 ─November 7, \n2022, a total of 21 cases of Mpox were reported during pregnancy and 2 cases were reported in \na recently pregnant person, which was defined as within 3 weeks of pregnancy. Among the 12 \nwith exposure data, 9 reported sexual contact and 3 reported household contact to a person \nwith Mpox. Pregnant people had similar signs and s ymptoms of Mpox as those among non-\npregnant people. Among pregnant people, 4 cases had general lesions during the pregnancy, \nbut none had lesions at the time of delivery. Tecovirimat was provided to 48% of cases during \npregnancy , with no adverse events (AEs) reported . None of the pregnant cases received post -\nexposure prophylaxis (PEP) with JYNNEOS. Outcomes reported to date have included 4 \nhospitalizations of pregnant people for Mpox indications . All were discharged while still \npregnant. No pregnant cases required intensive care, intubation, or unplanned delivery. To date, pregnancy outcomes have been reported among 3 patients. Of these, 2 were uncomplicated \nlive births with no transmission to the infant and 1 pregnancy resulted in a first trimester \nspontaneous abortion. Two recently pregnant persons experienced symptoms within 3 days of \ndelivery and their newborns developed lesions within a week. The exact timing of transmission \nfor these infant cases is unknown. \nIn another recent report,\n4 the characteristics of Mpox cases were assessed among 466 \ntransgender and gender diverse persons. In this analysis, 43% were transgender women, 42% \nwere gender diverse, and 15% were transgender men. Of the gender diverse persons, 96% \nwere assigned male sex at birth. The median age of the transgender and gender diverse \npersons with Mpox was 32 years and ranged from 18─ 71 years. Among the transgender and \ngender diverse persons with Mpox , 28% were Black, 28% were White, and 37% were Hispanic \nor Latino. About half of the transgender and gender diverse persons with Mpox were HIV -\npositive, which is similar to the percentage observed among all persons with Mpox. Among \ntransgender and gender diverse persons with Mpox , 84% reported recent sexual or close \nintimate partner contact. \nIn another recent report of 83 cases in children from May 17– September 24, 2022 ,5 there were \n16 cases in children aged 0─4 years, 12 cases in children aged 5─12 years , and 55 cases in \nchildren aged 13─ 17 years . Adolescents aged 13 ─17 years were overwhelmingly male and \nprimarily had sexual exposures, mirroring the epidemiology of cases overall. In younger \nchildren, cases were more evenly divided by sex and were associated with household contact, \nfrequently from an infected caregiver. While these findings are from a report analyzing data \nthrough September, investigation has continued in cases among children, particularly younger \nchildren, and findings have been similar. \nIn terms of vaccine doses administered to date, as of February 7, 2023, a total of 1,185,907 \ndoses were administered. This includes 732,725 first doses. First doses and overall doses \nadministered peaked in August at the same time when Mpox cases reported to CDC peaked. \nDoses administered ha ve declined substantially since August. In the first week of February, \n1,314 first doses and 1,243 second doses were administered. While one-third of Mpox cases \noccurred among B lack or African American persons, just 13% of first dose vaccine recipients \n4 https://www.cdc.gov/mmwr/volumes/71/wr/mm715152a1.htm?s_cid=mm715152a1_w \n5 http://dx.doi.org/10.15585/mmwr.mm7144a4 \n10 \n \n     \n     \n     \n     \n   \n \n \n \n        \n     \n  \n      \n    \n  \n \n     \n   \n  \n      \n   \n  \n \n   \n \n   \n \n \n       \n  \n \n   \n        \n \n  \n   \n \n    \n   \n       \n  \n  \n      \n    \n     \n   \n  \n \n      \n     were Black or African American. While 31% of Mpox cases were among Hispanic or Latino \npersons, just 22% of first dose vaccine recipients were Hispanic or Latino. Additionally, 29% of \nMpox cases were among White persons, while 52% of first dose vaccine recipients were among \nWhite persons. Hence, some substantial differences are observed by race and ethnicity when \ncomparing those who have been infected versus those receiving vaccine. \nJYNNEOS Vaccine Effectiveness \nAnna Chard, PhD, MPH (CDC/NCIRD) presented on JYNNEOS VE on behalf of the Vaccine \nTask Force of CDC's Mpox Response. The efficacy of JYNNEOS vaccine against Mpox has \nbeen inferred from animal and immunogenicity studies, but it has never been demonstrated in \nclinical trials. Additionally, prior to the multinational outbreak, there were no real -world \neffectiveness estimates for JYNNEOS against Mpox disease. Therefore, the following key \nquestions related to VE were developed: \n1. What is the effectiveness of JYNNEOS vaccine against Mpox disease for partial (1-dose) \nand full (2-dose ) vaccination? \n2. Are there differences in VE by route of vaccination administration? On August 9, 2022, an \nEmergency Use Authorization (EUA) was issued for intradermal administration of a 2-dose \nseries to increase vaccine supply, so it is important to examine the differences in VE by \nroute of administration. \n3. Are there differences in VE among persons with immunocompromising conditions? The populations most a t risk for Mpox disease are also at higher risk of immunocompromising \nconditions such as HIV . \n4. What is the duration of protection conferred from JYNNEOS vaccine? The duration of protection conferred by JYNNEOS vaccine is unknown. \nIn this presentation, Dr. Chard presented evidence for the first 2 questions ; however, evidence \nremains limited regarding VE among persons with immunocompromising conditions and the \nduration of protection from JYNNEOS vaccine. \nIn terms of vaccine performance, Dr. Chard reviewed a study on the incidence of Mpox among \nunvaccinated persons versus persons receiving ≥1 JYNNEOS dose in the US.\n6 For this \nanalysis, investigators used surveillance data from confirmed and probable Mpox cases, vaccine administration data ascertained from interviews and immunization registries, and \njurisdiction -specific  estimates of the vaccine- eligible population to compare Mpox instance \namong persons who were unvaccinated and those who had received either one or two JYNNEOS doses. There were 9,544 reported Mpox cases among men 18 ─49 years of age from \n43 US jurisdictions during the analysis period of July 31─ October 1, 2022. Investigators \nestimated weekly Mpox incidence for persons with partial (1 dose) and full (2 doses) vaccination \nand persons eligible but unvaccinated. The incidence rate ratio was calculated using negative \nbinomial regression controlling for week. Mpox incidence among unvaccinated individuals was \n7.4 (95% CI = 6.0– 9.1) times as high as persons receiving 1 dose of JYNNEOS vaccine . Mpox \nincidence among unvaccinated individuals was 9.6 (95% CI = 6.9– 13.2) times as high as \npersons receiving 2 doses of JYNNEOS vaccine. No difference was observed in vaccine \nperformance between subcutaneous and intradermal administration. \n6 Payne AB, et al. Reduced Risk for Mpox After Receipt of 1 or 2 Doses of JYNNEOS Vaccine Compared with Risk Among \nUnvaccinated Persons — 43 U. S. Jurisdictions, July 31– October 1, 2022. MMWR Morb Mortal Wkly Rep 2022;71:1560– 1564. \n11 \n \n      \n  \n   \n    \n  \n    \n     \n  \n \n  \n  \n    \n    \n     \n   \n      \n   \n \n    \n   \n    \n   \n   \n      \n \n \n    \n    \n    \n        \n    \n \n  \n \n   \n    \n   \n   \n \n  \n   \n       \n          \n   \n     \n  \n \n  \n   \n   \n  The New York City Department of Health and Mental Hygiene (NYC Health) examined the VE of \nJYNNEOS administered as PEP using a cohort evaluation of individuals ≥18 years of age \nidentified through contact investigations to a case patient with Mpox between March 22─ August \n24, 2022.7 PEP was defined as receiving the first dose of JYNNEOS within 14 days of exposure \nand prior to symptom onset. Case patients were defined as exposed individuals who developed \nsymptom onset within 21 days of exposure and had laboratory confirmation of Mpox. VE was \n77% among individuals who received PEP less than 14 days after their last exposure and 79% \namong individuals who received PEP less than 14 days after their first exposure. \nInvestigators in Israel evaluated the real -world effectiveness of a single subcutaneous dose of \nModified Vaccinia Ankara- Bavarian Nordic (MVA- BN), which uses the trade name JYNNEOS in \nthe US.8 This was a retrospective, observational cohort study based on data obtained from \nelectronic health rec ords (EHRs) from a single integrated healthcare organization in Israel. The \ncohort included 2,054 men who were eligible for vaccination on July 31, 2022 when the \nvaccination campaign began who had completed at least 90 days of follow- up. Specific e ligibility \ncriteria were males aged 18─ 42 years of age who were dispensed HIV pre-exposure \nprophylaxis ( PrEP ) for at least 1 month since January 1, 2022, or males aged 18─ 42 years who \nwere diagnosed with HIV and also were diagnosed with one or more sexually transmitted \ninfections (STIs) since January 1, 2022. The time period for this analysis spans July \n31─December 25, 2022 such that all participants were followed for 90 to 120 days after cohort \nentry. VE was estimated using Cox proportional hazards regression with vaccination status as a \ntime-varying covariate. The model adjusted for sociodemographic and clinical risk factors. \nDuring July 31─December 25, 2022 there were 5 cases among vaccinated individuals and 16 \ncases among unvaccinated individuals. The adjusted single- dose VE was 86% (95% CI: \n59%-95%) . \nIn the EPIC -COSMOS case -control study,9 data were used from EPIC ’s EHR platform , Cosmos, \nwhich includes records from over 169 million patients across the US. This was a case -control \ndesign in which cases were defined as patients with an Mpox diagnosis or a positive \northopoxvirus or positive Mpox virus laboratory result from the study period of August \n15─October 29, 2022. Controls were defined as patients with an instant HIV diagnosis or HIV \nPrEP prescription during the same study period and was determined based on the \nAdministration for Strategic Preparedness and Response ( ASPR) vaccine distribution guidance. \nVE was estimated using conditional logistic regression models, adjusting for a priori specified confounders. The analysis also was stratified to examine full and partial VE by route of \nadministration and immunocompromised status. Adjusted VE was 66% for full vaccination and \n36% for partial vaccination. Among individuals with no immunocompromising conditions, VE \nwas 76% for those fully vaccinated and 41% for those partially vaccinated. Although the \nanalysis was controlled for immunocompromising conditions, VE could not be estimate d among \nthis population because vaccine coverage was low. Less than 1% of immunocompromised \nindividuals were fully vaccinated. When examining VE by route of administration, very few \npatients were fully vaccinated with 2 subcutaneous doses or 2 intradermal doses. The 95% \nconfidence intervals were wide, but the point estim ates were similar to the overall estimate. For \nfully vaccinated persons with heterologous administration routes, VE was 75% , demonstrating \nthat 2 doses confers protection regardless of the route of vaccine administration. \n7 Unpublished data \n8 Sagy, Y. W. et al. Real -world effectiveness of a single dose of mpox vaccine in males. Nature Medicine \nhttps://doi.org/10.1038/s41591- 023-02229-3 (2023) \n9 Unpubl ished data \n12 \n \n     \n    \n   \n      \n  \n   \n  \n   \n     \n      \n  \n   \n   \n  \n \n   \n   \n      \n  \n   \n   \n \n   \n      \n     \n     \n    \n    \n   \n \n    \n \n \n \n \n        \n   \n    \n        \n   \n  \n  \n  \n       \n   \n \n  A multi- jurisdictional  case- control study is currently underway. This study examines VE among \nmen 18─49 years of age who have sex with men and live in 12 US jurisdictions. Cases are \nidentified through the jurisdictions ’ probable and confirmed Mpox case lists. Controls are \nselected from healthcare settings providing HIV PrEP or from STI clinics. Cases are matched to \ncontrols based on time point within 4 weeks of clinic attendance and jurisdiction. Jurisdiction \nstaff members collect data on participants ’ demographics, exposure history , and vaccination \nhistory using electronic surveys . Vaccination status of enrolled participants is confirmed using \nstate immunization registries. VE is estimated using multivariable logistic regression with \nrandom intercept for jurisdiction and adjusted for prior specified confounders. Notably, these are \ninterim results as data collection is still underway. Results indicate that VE is 76% for full \nvaccination among those without immunocompromising conditions . VE is 90% for ful l \nvaccination. At this interim stage, there were few individuals with partial vaccination or with \nimmunocompromising conditions. Therefore, data are not sufficiently powered to generate \nestimates for these strata. \nIn a case- control study in New York State (NYS), i nvestigators linked case surveillance data to \nthe immunization registry. Cases were adult male Mpox cases diagnosed during July \n24─October 31, 2022. Controls were adult male STI cases with rectal gonorrhea or primary \nsyphilis cases during the same time period. Cases and controls were matched on week of \ndiagnosis and VE was estimated using conditional logistic regression. VE was 68% for partial \nvaccination and 89% for full vaccination. \nIn summary, the existing body of evidence for VE of JYNNEOS against Mpox disease ranges \nfrom 66 % to 83% for full vaccination and 36 % to 86% for partial vaccination. This evidence \nindicates that the JYNNEOS vaccine is effective at reducing the risk of Mpox disease. Protection is provided by both 1 and 2 doses of JYNNEO S vaccine , but the highest protection is \nprovided by 2 vaccine doses regardless of administration route. Further research is needed to \nassess whether immunocompromised status modulates VE. Due to small numbers in this \npopulation across studies, there was insufficient power to generate VE estimates among \nimmunocompromised individuals. Additionally, because of a decline in Mpox cases and the \nlimited follow- up period from studies to date, further research is needed to assess the duration \nof protection conferred by JYNNEOS vaccination. \nJYNNEOS Vaccine Safety \nJonathan Duffy, MD, MPH (CDC/NCEZID) noted that while an MMWR report about JYNNEOS \nvaccine safety monitoring was published that included data collected through October 2022 , this \npresentation would include data through January 2023 collected using 3 surveillance systems : \n1) the Vaccine Adverse Event Reporting System (VAERS) , which is a national passive r eporting \nsystem ; 2) the Vaccine Safety Datalink (VSD), which perfor ms medical visit- based active \nsurveillance for pre- specified adverse events of special interest (AESI) in a population of more \nthan 10 million people; and 3) v -safe\nsm, which is a smartphone -based system that uses text \nmessaging to initiate web- based survey monitoring for AEs. AEs also were collected as part of \nsingle -patient Emergency Investigational New Drug (EIND) procedures for persons <18 years of \nage who were vaccinated before the JYNNEOS EUA was issued that allowed administration in \nthat age group. \n13 \n \n       \n    \n   \n    \n    \n      \n      \n  \n   \n \n    \n    \n  \n  \n     \n        \n      \n   \n   \n   \n    \n      \n \n   \n   \n \n    \n    \n      \n \n \n   \n   \n    \n    \n   \n   \n      \n  \n \n \n \n \n \n \n \n \n \n \n  \n  \n \n \n \n \n \n \n \n \n  \n To provide an overview of the VAERS findings, as a reminder VAERS is the national passive \nsurveillance system for AE reporting after vaccination. VAERS accepts reports from healthcare \nproviders (HCP) , vaccine manufacturers, and the public. VAERS collects data on any AE \nfollowing vaccination, be it coincidental or truly caused by a vaccine. The report of an AE to \nVAERS is not documentation that a vaccine caused the event. The FDA issued an EUA for \nJYNNEOS on August 9, 2022 that required mandatory reporting to VAERS of vaccine \nadministration errors , regardless of whether they were associated with an AE; serious AEs \n(SAE), irrespective of attribution to vaccination; c ases of cardiac events, including myocardi tis \nand pericarditis; and cases of thromboembolic events and neurovascular events. \nThe analysis presented during this session include d VAERS reports received and processed by \nJanuary 20, 2023. AE reporting rates were calculated by dividing the number of V AERS reports \nby the number of vaccine doses administered in the US. During the period May 22–January 13 , \n2023, a total of 698,188 people received Dose 1 and a total of 426,980 received Dose 2 for a \ntotal of over more than 1.1 million doses administered. VAERS received 1,817 reports after \nJYNNEOS. Most of these reports were for male adults 18─ 64 years of age and for JYNNEOS \ngiven alone without other vaccines on the same day. Most reports were about Dose 1. The most \ncommon route of administration was intradermal, followed by subcutaneous. Intramuscular \nadministrations also were reported, most of which were reported as an error in the rout e of \nadministration. Vaccine administration errors were the subject of 50% of all JYNNEOS VAERS \nreports. Of these, 96% did not report an adverse health event. Vaccine administration errors \nhave been reported for JYNNEOS about 3 times more often with intradermal compared to \nsubcutaneous administration. The most common issue reported with intradermal administration \nhas been absence of a wheal without vaccine leakage (42%) . CDC's I nterim Clinical \nConsiderations for use of JYNNEOS state that absence of a whea l without vaccine leakage may \nbe counted as valid administration . After excluding reports of vaccine administration errors \nalone, adverse health events were reported to VAERS at a similar rate for subcutaneous and \nintradermal administration. The most common types of events differed slightly by route of \nadministration. Overall, the most common adverse health events reported to VAERS for adults \nwere consistent with those reported in pre -licensure clinical trials. \nAn SAE event is defined as a report of the occurrence of any of the following: d eath, a life -\nthreatening AE, hospitalization, a persistent or significant incapacity or substantial disruption of \nthe ability to conduct normal life functions, a congenital anomaly or birth defect, or another \nimportant medical event that based on appropriate medical judgement may jeopardize the \nindividual and may require medical or surgical intervention to prevent one of the outcomes listed above. About 1% of reports to VAERS after JYNNEOS were classified as SAEs . SAEs were \nreported at a rate of 22 reports per million doses administered. SAEs reported to VAERS after \nJYNNEOS are listed here: \nMyocarditis (n=5) \nDeath (n=2)** \nPericarditis (n=2) Urticaria (n=2) Appendicitis \nAseptic meningitis \nAsthenia Atrial fibrillation Cellulitis \nChest pain Dehydration \nIdiopathic thrombocytopenic purpura Injection site discoloration Injection site pain \nInjection site scar \nMethemoglobinemia Retrograde amnesia Rhabdomyolysis \nSudden hearing loss \n14 \n \n  \n    \n      \n \n  \n   \n \n   \n  \n    \n    \n   \n  \n      \n     \n     \n     \n   \n     \n    \n  \n      \n   \n    \n    \n \n \n    \n       \n     \n   \n \n   \n \n     \n      \n  \n  \n    \n      \n    \n   \n \n  \n \n          \n \n       \n Not all AEs that occur after vaccination are caused by the vaccine. Two deaths were reported to \nVAERS after JYNNEOS administration. The local Medical Examiners (MEs) determined and \nreported the causes of death in these cases to be drowning and cocaine toxicity. Hospi talization \nfor myocarditis or pericarditis were the most commonly reported SAEs. T he single cases of the \nother conditions reported do not suggest safety signals for any of these conditions. \nTo discuss the myocarditis and pericarditis findings in more detail, m yocarditis and pericarditis \nhave occurred following either primary vaccination or revaccination with live vaccinia virus \nsmallpox vaccines in the past. The mechanism is poorly understood, and it was unknown \nwhether persons who received JYNNEOS might experience myocarditis or pericarditis. In this \nepidemiologic analysis, the cases have been classified into 2 groups. The first is myocarditis \nwith or without pericarditis and the second is acute pericarditis alone. The surveillance risk interval is defined as symptom onset within 30 days after vaccination. In VAERS, 2 cases of \nmyocarditis were reported after Dose 1 for a rate of 2.75 cases per million persons vaccinated , \nwhile 3 cases were reported after Dose 2 for rate of 6.74 per million. In the VSD popul ation, \nthere were 37,646 people who received at least one dose of JYNNEOS. There was 1 case of \nmyocarditis observed after each dose. The VSD incidence rate estimates have wide confidence \nintervals that range from about 1 to 250 cases per million. These confidence intervals overlap \npublished historical population background rates, which range from 2.7 to 21.6 cases per million persons during a 30- day period. For context, the published historical rates after live replicating \nsmallpox vaccines have ranged from 70 cases per million after Dryvax in a 2002 military cohort \nstudy, up to 5,000 per million cases after ACAM2000 in a 2018 military cohort study. In \nsummary, the VAERS and VSD data do not suggest an increased risk for myocarditis following \nJYNNEOS compared to expected published background rates,\n10 but the possibility of a small \nrisk cannot be excluded. \nIn a similar analysis for pericarditis , there were a total of 6 cases reported to VAERS, only 2 of \nwhich were classified as serious due to hospitalization. There were 4 cases after Dose 1 and 2 \ncases after Dose 2 for a rate up to 5.5 cases per million persons during a 30-day period. There \nwere no cases identified in the VSD population. The VAERS reporting rate for pericarditis is \nsimilar to expected published historical background rates and less than that observed after live \nreplicating smallpox vaccines in one military cohort study.11 \nThe v -safesm platform is a smartphone -based system that uses text messaging to initiate web-\nbased survey monitoring for AEs following vaccination. The data from v -safesm are used to \ncharacterize the basic safety profile of a vaccine when given outside of a clinical trial setting and \ncan facilitate reporting to VAERS for medically attended adverse events (MAAEs). This system \nis meant to supplement CDC’ s other vaccine safety monitoring systems, VAERS and VSD. In \nterms of the characteristics of v -safesm participants, there were 181 active participants, defined \nas having completed at least one survey between November 16, 2022 – January 29, 2023 , all of \nwhom were adults and the majority of whom were male. Additional characteristics are shown on \nthe following tables: \n10 References: Halsell, et all. DOI: 10.1001/jama.289.24.3283; Oster, et al. DOI:10.1001/jama.2021.24110; Mandra, et al. DOI: \n10.1017/dmp.2020.478 \n11 References: Imazio, et al. DOI: 10.1136/hrt.2006.104067; Kumar, et al. DOI: 10.1159/000445206; Engler, et al. \nDOI:10.1371/journal.pone.011828 \n15 \n \n   \n \n     \n   \n      \n   \n    \n \n       \n      \n     \n   \n   \n         \n          \n   \n    \n \n       \n   \n    \n    \n  \n        \n  \n \n    \n   \n   \n    \n   \n     \n \n  \nIn terms of the percentage of participants who reported reactions or health impact events at \nleast once during D ays 0 to 7 after vaccination by dose, a bout 80% reported any injection site \nreaction and 5% sought medical care. No participants reported SAEs . The most common type \nof injection site and systemic reac tion reported overall was redness at the injection site, reported \nby 64% of participants . The most common systemic reaction was fatigue, reported by 40%. \nRegarding information about AEs in persons <18 years of age , CDC facilitated single -patient \nEIND authorization from the FDA to make JYNNEOS available for persons <than 18 years of \nwhen needed prior to the JYNNEOS EUA being issued on August 9, 2022 that allowed wider \nuse in this age group. CDC solicited information from vaccine providers about AEs occurring in \ntheir patients during the 28 days after each dose. Persons vaccinated under the EIND ranged in \nage from 4 months to 17 years and 58% were male. AEs were reported for 10 (18%) of 57 \npeople after Dose 1 and 5 (21%) of 24 people after Dose 2. The types of events reported \nincluded injection site reactions of pain, erythema, swelling, and induration and systemic AEs of \nfever, fatigue, and headache. No SAEs were collected in this project. \nVAERS also was used to collect data on persons <18 years of age . JYNNEOS was \nadministered to 1,245 persons <18 years of age in the US during the surveillance period. \nVAERS received 25 reports for this age group. Vaccinated persons ’ ages ranged from 12 \nthrough 17 years. Reports of vaccine administration errors accounted for 84% of these reports, \nwith the most common being intradermal administration instead of subcutaneous, which is the \nauthorized route for this age group. The only AE reported was 1 person with syncope and no \nSAEs were reported. \nThe overall conclusions about vaccine safety monitoring are that JYNNEOS post -licensure and \npost-authorization vaccine safety surveillance findings to date are consistent with those \nobserved in clinical trials. No new or unexpected safety concerns have been identified. SAEs \nwere rare among adults and none have been identified among persons <18 years of age . \nVAERS and VSD data taken together do not suggest an increased risk for myocarditis or \npericarditis following JYNNEOS, but the possibility of a small risk of myocarditis cannot be \nexcluded. \n16 \n \n    \n \n        \n     \n \n     \n  \n     \n     \n      \n \n     \n      \n     \n   \n \n  \n    \n \n \n \n   \n  \n      \n   \n    \n    \n     \n     \n     \n      \n          \n     \n      \n    \n \n   Mpox Vaccine Acceptability and U ptake from Cross-S ectional S urveys \nKevin P. Delaney, PhD, MPH (CDC/NCHHSTP) presented Mpox vaccine acceptability and \nuptake findings from cross -sectional surveys from among clinicians and vaccine interest, intent, \nand uptake among the general population and populations disproportionately affected by the \ncurrent outbreak on behalf of the CDC Community Engagement Task Forc e. One source of \ninformation for this is surv eys of clinicians . CDC has worked with Sermo to get some insights on \nthis. Sermo is an online community of more than 1.3 million clinicians. At the beginning of \nAugust, the company conducted what they call a “B arometer ” survey of physicians around the \nworld with over 1,000 physicians total.12 During this session, Dr. Delaney p resented data from \nthe 415 US -based clinicians in that survey. He highlighted that in early August 2022 , the \nmajority of clinicians surveyed wanted more access to Mpox vaccine. At short follow -up was \nconducted on September 12, 2022 at CDC’s request that found both high vaccine demand and \nacceptability, with 76% of respondents saying they knew where to send patients for JY NNEOS \nvaccine. More importantly, 86% wanted to be able to offer vaccine in their practice. \nIn terms of information from affected populations, this table provides an outline and overview of \nthe 4 surveys conducted by CDC and partners during the current out break : \nThe first survey is one that CDC conducted in partnership with Porter Novelli. Porter Novelli is a \ncontractor who conducted 4 online general population surveys of US adults through the months \nof August, September, October, and December 2022 on knowledge, attitudes, and beliefs of \nMpox -related topics. The data are weighted to match US Census proportions for age, gender, \nregion, race, ethnicity, and education. They also ask a question about whether the respondent \nconsidered themselves to be a membe r of the lesbian, gay, bisexual, transgender, queer or \nquestioning,  or other ( LGBTQ+ ) community. The December survey had the largest sample and \nasked several questions specifically designed to directly measure Mpox vaccine acceptability and value. In this general population survey, very few people overall disagreed with the \nstatement that “The monkeypox vaccine is safe. ” Although many of the general population, even \nthose identifying as part of the LGBTQ+ community , said they did not know. For the current \noutbreak, which overwhelmingly has affected gay and bisexual men, 51% of those who \nidentified as LGBTQ+ thought the vaccine was safe and 50% of that group also thought it was \nimportant to get the Mpox vaccine to protect themselves. For the second q uestion, it is \n12 https://app.sermo.com/barometer/unitedstates \n17 \n \n      \n    \n \n    \n      \n  \n     \n         \n      \n   \n       \n     \n    \n   \n \n \n    \n   \n   \n     \n     \n     \n      \n    \n \n    \n      \n      \n    \n  \n  \n     \n      \n    \n     \n   \n \n   \n     \n    \n     \n   \n    \n   \n     \n   \n   \n  \n \n   \n   interesting that 31% of those who did not identify as LGBTQ+ or a member of the LGBTQ+ \ncommunity also felt it would be important to get the Mpox vaccine to protect themselves. \nThe American Transformative HIV Study (AMETHST )13 collected data from the community most \naffected by the current outbreak (e.g., gay, bisexual, and other MSM) . AMETHYST is a National \nInstitutes of Health ( NIH)- funded online cohort that will eventually include 5,000 sexual minority \nmen. This is a diverse group with higher risk of HIV acquisition than the general population, \neven of sexual minority men, by design. The study will be recruiting such that the cohort is no \nmore than 50% non- Hispanic Whites, the majority -minority, by race and ethnicity. About 60% of \nthe cohort will have reported recent methamphetamine use, which increases bio- behavioral \nvulnerability to HIV. To achieve the objective of enrolling 5,000 such men, the plan is to screen \nover 30,000 respondents with an online eligibility survey. Questions about Mpox knowledge, \nvaccine uptake, and behavior change have been added to the screening enrollment survey. The \ndata presented during this session were from the first 8,500 participants screened from August \n6─November 15, 2022. \nRegarding the question, “How mu ch have you worried about Mpox infection over the last 2 \nweeks?” the number who said they worried some or more than half of the days decreased from \n66% in August to 35% in November and the number who said they never worry increased from 34% in August to 66.4% in November. While Mpox concern decreased over time, about one-\nthird of participants remain concerned about Mpox. Over 85% of respondents remain interested \nin vaccine. Vaccine coverage doubled between August and September but then flattened out, \nwhich is consistent with vaccine administration data. As of November, 30% of those recruited \nreported having received at least 1 dose. However, the proportion of people reporting the intent \nto take vaccine remained strong and there was minimal increase in the proportion of people who \nsaid they were unlikely to get vaccinated. Overall, 85% of those enrolled in the survey so far are \neither vaccinated or reported being likely to get vaccinated. In terms of vaccine uptake by race \nfrom August to November 2022 among AMETHYST participants surveyed at the peak of the \noutbreak, Black men had the highest proportion reporting receipt of at least 1 dose of vaccine. \nIn August, Black participants had higher vaccine coverage than participants from other racial and ethnic groups but did not see the “doubling” in vaccine coverage that were reported overall. \nIt also is important to think about other communities in terms of equity. AMETHYST may be the \nonly or best source for this. There was much lower uptake of vaccine for gender div erse \npersons and for those who do not identify as gay. Moving forward with plans to improve equity \nand access, it is important to do a better job of specifically marketing and creating demand for \nthose groups as well as Black men. \nThe American Men’s Internet Survey (AMIS) is an Emory University annual online cross -\nsectional survey of people who were born and currently identify as male that is typically \nconducted with recruitment from October to February of a given year. In August 2022, \ncolleagues at Emory University conducted a special one- time survey that recontacted men who \nparticipated in the 2021 AMIS survey cycle interviewed between October 2021 and February \n2022 to explore knowledge, attitudes, and practices related to the US Mpox outbreak. The \nsurvey was conducted between August 5 -15, 2022 during the peak of the current outbreak.\n14 \nFor those interested, Emory posted all of the questions that were asked in the August survey \nonline. There are questions in this survey about vaccine knowledge, access , and desire to be \nvaccinated; barriers to vaccination; and sources of information on Mpox. As published in an \nMMWR that first appeared online on August 26th, 53% of AMIS participants reported concern \n13 https://grants.nih.gov/grants/guide/rfa- files/RFA -AI-21-018.html \n14 https://www.cdc.gov/mmwr/volumes/71/wr/mm7135e1.htm \n18 \n \n    \n          \n    \n  \n       \n     \n \n  \n  \n   \n \n \n \n \n   \n   \n  \n   \n \n  \n  \n \n    \n   \n \n   \n      \n  \n    \n  \n   \n  \n  \n \n      \n     \n   \n   \n     \n \n  \n \n \n  about getting Mpox at that time. At that time, 18.6% of MSM surveyed reported having received \nat least 1 dose of vaccine. This is consistent with the AMETHYST data. That MMWR also \nreported higher vaccine uptake for Black men compared to all other racial groups, lower vaccine \nuptake in more rural areas relative to urban areas, and lower vaccine uptake in the South and \nMidwest. At the time this was published, the MMWR called for more equitable vaccine delivery. \nThese quotes are from the discussion section: \n“Equitable vaccine program implementation involve…, engaging diverse partners \nalready working with special populations, delivering vaccines through mobile outreach \nand pop- up events, and diversifying times and locations for vaccine administration” \n“Expanding vaccine availability geographically, including diversifying vaccination locations to include nonurban areas, can help ensure that those who need vaccination \nhave access to it.” \nJust 4 days after publication of the MMWR , the White House announced plans to support \nexpansion of vaccine access th rough distribution to groups working to provide vaccine at large \nevents and in spaces where they could reach populations who otherwise might not have \naccess.\n15 The Mpox Vaccine Equity Pilot Program (VEPP) was created to: 1) support innovative \nways to address vaccination disparities; 2) encourage vaccination coordination between health departments and community -based organizations (CBOs); and 3) promote innovation to \nstrengthen existing vaccination infrastructure. The VEPP provided additional vaccine above the \noriginal allocation to 15 jurisdictions, 14 states, and Puerto Rico for 28 different vaccination programs and events. These were beyond the threshold supplies provided to states. This \nproject delivered nearly 25,000 doses of vaccine at special vaccine equity events. \nThe 2022- 2023 AMIS is still recruiting. These data are from an abstract developed for \nsubmission to the International AIDS Society (IAS) meeting but are not yet published. \nRecruitment began in early October and by the end of December, over 3,000 men had been \nenrolled. At that point, 33% reported that they had received 1 dose of vaccine. Again, very \nconsistent with the AMETHYST data for November and December. Vaccine uptake was \nassociated with Mpox awareness and concern and also with factors that might be indicative of \nconcern for or awareness of sexual health and access to sexual health services overall, \nincluding HIV care, STI testing, and HIV PrEP use. \nA study conducted by the CDC and the San Francisco Department of Public Health (SFDPH) \nspecifically recruit ed another special population of people experiencing homelessness in San \nFrancisco. This study was fielded from October 23─November 5 and sought to understand \nMpox vaccine coverage and acceptability among peopl e experiencing homelessness. This \nstudy also collected blood to assess seroprevalence in this community, though Dr. Delaney did \nnot discuss that during this session. The take- home from this analysis is that 56% of those who \nreported any sexual risk and 74% of MSM, said that they would accept Mpox vaccination. \nAgain, consistent with the AMETHYST data. \n15 https://www.whitehouse.gov/briefing- room/statements -releases/2022/08/30/fact -sheet -white -house- monkeypox -response- team -\nannounces -new-plans -to-support -large- lgbtqi -events -and-equity -interventions -to-reach- communities -at-highest -risk-of-\ncontracting- the-virus/ \n19 \n \n  \n \n  \n    \n    \n    \n   \n  \n   \n    \n     \n \n \n      \n     \n     \n  \n    \n    \n       \n   \n    \n  \n \n   \n   \n   \n   \n  \n  \n    \n   \n \n \n     \n \n  \n  \n \n   \n \n      \n \n   \n \n  Interim Clinical Considerations \nRosalind Carter, PhD (CDC/NCIRD) provided a brief overview of CDC’s Mpox vaccine Interim \nClinical Considerations (ICC) that were developed to guide vaccine implementation during the \nMpox outbreak. It is important to remember that the ICC is a living document . As the \nepidemiology of the outbreak evolved and as feedback was received from the field in terms of \nnew questions and concerns, the guidance was updated or clarified. The latest ICC updates \ncontinue to emphasize the importance of vaccination before exposure for those with the highest \npotential for exposure to Mpox, the importance of identifying and vaccinating persons living with \nHIV or who have other causes of immunosuppression who have had recent or anticipate \npotential Mpox exposure, and including explicit language stating that the definitions of risk \ngroups also include adolescents. \nFrom the beginning of the 2022 Mpox outbreak, the US Government (USG) recognized that \nMpox vaccine availability was the critical strategy to limit the rapid spread of Mpox. Two \nvaccines may be used for prevention of Mpox and were available from the Strategic National \nStockpile (SNS) . They included the JYNNEOS vaccine approved for prevention of smallpox and \nMpox and licensed for use among persons 18 years of age and older. On August 9, 2022, FDA \nissued an E xpanded Use Authorization (EUA) for intradermal administration among persons 18 \nyears of age and older. That is the primary vaccine being used during this outbreak in the US. \nACAM2000 is an alternative to JYNNEOS and approved to protect against both smallpox and \nmonkeypox. While it is available, it has not been used duri ng this outbreak due to the higher risk \nof SAEs . \nOn June 28, 2022, the federal government announced an enhanced nationwide strategy to \nvaccinate and protect people at risk for Mpox, prioritize vaccines for areas with the highest \nnumber of cases, and provide guidance to state, tribal, local, and territorial health officials to aid \nplanning and response efforts. Multiple federal agencies, including the ASPR, SNS, Biomedical \nAdvanced Research and Development Authority (BARDA) , CDC, and FDA are working closely \nwith partners to ensure there are enough vaccine doses available to vaccinate all people for whom vaccine is recommended. There are 2 primary strategies, which are 1) vaccination of \nindividuals after known or presumed exposure to someone with Mpox ; and 2) vaccination prior \nto exposure among persons at high risk for potential exposure. \nFor PEP in the first strategy , CDC has defined people eligible for vaccine in the ICC as follows: \nPeople who are known contacts to a person with Mpox, and identified by public health \nauthorities as a “contact” from case investigation, contact tracing, or risk exposure \nassessment ; or \nPeople who are aware that a recent (within the past 14 days) sex partner was diagnosed \nwith Mpox ; or \nGay, bisexual, other MSM , and transgender or non- binary people (including adolescents ) \nwho have had sex with multiple partners , at a commercial sex venue, or sex in an \nassociation with an event, venue, or defined geographic area where Mpox transmission is \noccurring. \n20 \n \n  \n  \n \n \n     \n   \n      \n  \n  \n   \n  \n  \n \n  \n   \n  \n  \n \n \n   \n    \n    \n  \n \n  \n \n  \n  \n   \n    \n  \n     \n     \n    \n  \n \n    \n    \n   \n    \n \n    \n       \n \n      \n      \n    \n   \n    \n  For PrEP in the second strategy, CDC has defined eligible groups in the ICC as those groups \neligible for vaccination prior to Mpox exposure who either have highest potential risk for \nexposure or who anticipate potential exposure to Mpox : \nGay, bisexual, and other men who have sex with men, and transgender or nonbinary people (including adolescents) who, within the past 6 months, have had: \n− A new diagnosis of one or more sexually transmitted diseases (e.g., chlamydia, gonorrhea, syphilis); \n− More than one sex partner \nPeople who have had any of the following in the past 6 months: \n− Sex at a commercial sex venue; or \n− Sex in association with a large public event in a geographic area where mpox transmission is occurring \nSexual partners of people with the above risks \nPeople with HIV † infection or other causes of immunosuppression who have had recent or \nanticipate potential mpox exposure \nPeople in certain occupational exposure risk groups (laboratory personnel working with orthopoxviruses ) \nThis is all in accordance with the ACIP 2022 recommendations. It is important to note that although the language describes the highest risk groups in an effort to improve equitable access \nto Mpox vaccines, persons who request vaccination can receive it without having to attest to \nmeeting any of these specific criteria. \nHealth equity principles outlined in the interim clinical guidance are incorporated into the National Vaccine Strategy as well as local implementation efforts. Some of these principles \ninclude engaging people from affected communities in the planning and design of vaccination \nefforts ; using non- stigmatizing, plain language; reiterating privacy of information and how data \nwill be used; engaging diverse partners already working with special populations ; bringing \nvaccines to where affected populations are (e.g., pop- up events, mobile outreach); offering \nmultiple appointment times and flexible walk -in opportunities, including evenings and weekends \nto improve vaccine accessibility ; leveraging clinical venues such as the Federally Qualified \nHealth Centers (FQHCs) that serve people who have historically had less access to primary \ncare, sexual health clinics, transgender health clinics, and pharmacies to deliver vaccines; and \nminimizing systems that are first come, first -served. \nLooking quickly at the data, almost 1.2 million doses were administered and reported to CDC \nthrough February 7, 2023. This includes 734,000 first doses and 452 second doses. During the \nweek of August 7- 13, the EUA for intradermal administration was introduced. At tha t same time, \nadditional vaccine vials were released from the SNS and provided to the states. Intradermal \ndosing greatly expanded the number of people vaccinated with first and second doses during \nthe peak of the outbreak when demand was highest. Looking at data comparing Mpox cases to \nthose vaccinated by race and ethnicity and whether vaccine equity improved over time, notably \ncompleteness for race and ethnicity data in vaccine administration database was very good quality. Over 91% of this information was completed. Summariz ing the overall data from May \nthrough the end of January 2023 compared to the time periods of mid-June to mid -July and mid-\nJuly to mid -August, the proportion vaccinated who were Hispanic increased from 19% to 23% \nand the proportion of people vaccinated who were Black non- Hispanic increased from 7% to \n13%. While t hese proportions were maintained over time, improvements in vaccine equity in \nsubsequent months have been modest . It is important to note that the se data summarize the \n21 \n \n     \n    \n \n \n   \n  \n  \n   \n   \n   \n  \n  \n   \n     \n  \n \n \n    \n  \n    \n \n \n  \n    \n  \n    \n       \n      \n  \n   \n  \n  \n    \n  \n    \n     \n   \n    \n    \n \n  \n \n     \n     \n    \n   \n   \n     \n     \n    \n   national picture and individual jurisdictions, including many of the highest burden states that \nhave made substantial progress in addressing equity gaps. Nonetheless, there is much work \nahead in implementation to improve vaccine equity. \nTo highlight a few elements of the current vaccine implementation as best practices for future \noutbreaks , vaccine strategies and implementation were adapted to local situations, local \nepidemiology, and population needs. This included adapting the eligi bility criteria for local \ncontexts. Some examples of this are that some states included sex workers in their definition of \nvaccine eligibility. Many others removed sexual orientation labels from eligibility criteria and \nreduced potential stigma by allowing people to self -attest to eligibility. The interim guidance for \neligibility also evolved as the epidemiology , which was very dynamic, changed over time. CDC \nrecognizes that vaccination offered in the context of broader prevention activities, as well as \nsexual health care, including HIV testing and PrEP initiation, increased access to vaccines as \nwell as acceptance of vaccines. The importance of the key role that CBOs had cannot be \nemphasized enough in the success of vaccine implementation , both as trusted messengers and \nin logisticians in helping set up vaccine events in their neighborhoods and communities. It also \nis important to highlight the importance of planning resources for data collection, including \ncollecting vaccine status and dates of vaccination on monkeypox reporting forms, which allowed \nCDC to measure vaccine performance early in the rollout. Includ ing race and ethnicity data on \nvaccination reports, including on reports shared with CD C, is essential in driving program \nactions and course correction. \nIn addition to the success stories, there were many challenges, most notably the limited supply \nof vaccine at the peak of the outbreak in mid- July when demand was high. The intradermal \nroute of administration was an important public health intervention, increasing the vaccine \nsupply 300% to 500% when it was most needed. CDC’s ASPR colleagues handled the complex \nlogistics of moving JYNNEOS vaccine from the federal SNS to the jurisdictions. However, at the \nbeginning, the SNS was limited to only 5 shipments per week during the outbreak peak, leaving \nthe jurisdictions to manage redistribution to providers in critical areas. However, within about 6 \nweeks, ASPR was able to increase their shipping capacity to provide directly to providers. The \nchange from subcutaneous to intradermal administration required jurisdictions to provide skills \ntraining to vaccinators. However, on average, these jurisdictions were able to begin implementation of intradermal within 2 to 3 weeks of the EUA, which was a significant \naccomplishment and heavy lift. Initially, health departments and public clinics were the primary \nvaccine providers, providing more than 50% of all vaccinations. As the outbreak has subsided, \nthe jurisdictions have increasingly engaged STI and HIV care providers, as well as pharmacies \nin some states to take on these roles. Despite these challenges, it is important to acknowledge \nthe dedication and the hard work of the jurisdictional health departments that are truly \nresponsible for the successful implementation of Mpox vaccines. \nEtR: Use of JYNNEOS During Mpox Outbreaks \nAgam Rao, MD (CDC/NCEZID) presented the EtR Framework for vaccination with JYNNEOS \nvaccine during any monkeypox outbreak that could be spread through travelers from countries \nwhere it is endemic, imported animals such as prairie dogs or other animals, et cetera . It is \nimportant to understand that even though a vote is being proposed for JYNNEOS for any \noutbreak, the current outbreak is not over and people are encouraged to continue to be \nvaccinated based on the ICC that Dr. Carter summarized for specific populations for whom \nJYNNEOS is recommended during the current outbreak. Dr. Rao cautioned that this \npresentation included photographs that might be difficult for some viewers and that she would \nprovide advanced notice before showing them. \n22 \n \n     \n   \n  \n        \n     \n      \n \n     \n     \n \n \n      \n     \n    \n \n     \n  \n     \n   \n    \n    \n   \n    \n    \n     \n         \n      \n     \n   \n       \n \n     \n   \n    \n  \n     \n  \n      \n    \n       \n  \n \n \n   \n    \n   \n  \n       \n   \n   \n   \n  As a reminder, the EtR F ramework is a structure to describe information considered in moving \nfrom evidence to ACIP vaccine recommendations. It provides transparency around the impact of \nadditional factors on deliberations when considering a recommendation. There are 7 Et R \ndomains : Public Health Problem, Benefits and Harms, Values, Acceptability, Equity, Feasibility, \nand Resource Use. Dr Rao presented the WG’s interpretation of the data for each of these \ndomains and the response to the associated questions for each domain. The EtR question is : \nDoes ACIP recommend the2- dose* JYNNEOS vaccine series for persons aged 18 years \nand older at risk of Mpox during an Mpox outbreak? § \n*Dose 2 administered 1 month after Dose 1 \n§Public health authorities will determine whether there is an Mpox outbreak ; a single case may be considered an Mpox \noutbreak at the discretion of public health authorities. Other circumstances in which a public health response may be \nindicated include ongoing risk of introduction of Mpox into a community due to disease activity in another geographic area. \nIn terms of the P ublic Health Problem domain, there have been several notable public health \nevents involving Mpox since it was first recognized in humans in 1970. Early cases were in rural \nsettings in certain forested regions of Africa where the presumed animal reservoirs reside. The \nfirst outbreak outside of Africa occur red in the US in 2003 from pet prairie dogs that were co-\nhoused with infected small mammals from Ghana. There were 47 cases associated with that \noutbreak. Going forward, cases continue to occur in Africa. The 9 African countries are the \ncountries where we know that cases had occurred. Cameroon, Central African Republic, Côte \nd'Ivoire, Democratic Republic of Congo, Gabon, Liberia, Nigeria, Republic of Congo, and Sierra Leone. In 2017, there was a large outbreak in Nigeria involving 17 states . At that time, it was \nconsidered a very large outbreak involving 138 cases. During 2018─2021, there were imported \ncases in travelers from Nigeria to various countries, to the UK and Israel in 2018, and to the UK \nand Singapore in 2019. In 2021, there were 3 cases, 2 of which occurred in the US. In 2022, a \nmultinational outbreak occurred. All of this to say that Mpox does seem to be of public health significance and importance. There have been a lot of cases, including a reemergence of \nhuman cases in recent years after decades of no reported cases in some countries. \nEven before the 2022 multinational Mpox outbreak , investigations for even a single case of \nMpox have been intense. During the July 2021 investigation, in one of the investigations in the \nUS 223 contacts had to be monitored. Fortunately, there were no high- risk exposures or \nsecondary transmissions. There were a lot of contacts, including flight crew and fellow passengers on inte rnational and domestic flights and friends of the affected patient and a \nrideshare driver . All of these individuals were monitored by public health authorities. There were \n2 imported cases to the UK in 2019 and 2021 that resulted in secondary infections. In 2019, a \nHCW developed Mpox after presumed exposure while changing the bedding of an Mpox \npatient . In 2020, 2 household contacts of an Mpox patient developed Mpox. This outbreak is \nobviously involved in many cases that peaked in early August . Case counts are decreasing at \nthis time, but this outbreak is not over. \nThe typical presentation manifestation of Mpox during the current outbreak are small, firm, \ndeep- seated,  well-circumscribed lesions that can occur on the palms , soles, and other parts of \nthe body. They often have been scattered or focused on one body part, most commonly the \ngenitals. Prodromal symptoms, including fever and lymphadenopathy, have inconsistently occurred. When lesions have occurred in the peri anal or genital region, the pain from lesions \nhas been particularly pronounced. Rectal pain, abdominal pain, rectal bleeding, and tenesmus \nhave all been reported. Typically, symptoms resolve with supportive care alone, including pain \ncontrol. However, severe manifestations are occurring in some patients who have severe \noutcomes. Severe manifestations include ocular lesions, neurologic complications, \n23 \n \n     \n      \n        \n    \n  \n   \n   \n     \n  \n \n    \n   \n   \n   \n  \n     \n    \n      \n    \n   \n    \n      \n   \n \n  \n   \n  \n   \n     \n    \n      \n  \n     \n       \n       \n          \n     \n    \n        \n       \n   \n     \n       \n      \n  myopericarditis, and certain mucosal lesions that can affect patients regardless of immune \nstatus. Myopericarditis cases have been seen in people who developed Mpox . not just in \nindividuals. Keratitis and conjunctival ulcer are associated with ocular Mpox. Ocular lesions can \nbe very serious and can even cause blindness, as in other countries where classic Mpox has \noccu rred in Africa. Myopericarditis and neurologic complications have been reported in a small \nnumber of patients who are uncertain of the reasons for this. It has occurred in individuals who \nhave been immunocompetent. Encephalitis and transverse myelitis have occurred in patient s \nwith Mpox. When lesions occur on certain mucosal surfaces (e.g., urinary meatus, penis ) they \ncan cause complications, including obstruction. \nLesions can be severe, necrotic , and require consultation from medical subspecialists such as \nurologists, gastroenterologists, and general surgeons depending upon the location of the \nlesions. While these are considered severe manifestations, the most severe and the life-\nthreatening lesions occur in patients with severe immunocompromise. Patients who are \nseverely immunocompromised due to advanced HIV in particular have had the most severe \nmanifestations of Mpox during the current outbreak. The etiology is believed to be uncontrolled \nviral spread in severe ly immunocompromise d patients . Dr. Rao shared some images to illustrate \nthe progression of illness and how different the lesions in these patients can be from the typical \npresentation. Medical therapeutics such as t ecovirimat and brincidofovir may be helpful, but an \noptimized immune system through antiretroviral therapy , temporary halting of immunomodulator \ntherapies , or some other mechanism is still the most critical aspect of care. Deaths have \noccurred because of these illnesses, often many weeks after hospitalization because of the \nprogression and despite therapeutics. Therefore, the WG determined Mpox outbreaks to be of \npublic health importance based on all of the data presented . \nRegarding the Benefits and Harms domain, there are early estimates and population- based \nestimates of VE. Vaccine performance has been evaluated through comparison of incidence of \nMpox between vaccinated and unvaccinated persons in 43 US jurisdictions. Mpox incidence \namong unvaccinated was 7.4 times that among persons who received only 1 dose of JYNNEOS \nvaccine ≥14 days earlier , and 9.6 times that among persons who received Dose 2 ≥14 days \nearlier . Population -based adjusted measures of VE using EMRs also have been performed . A \nretrospective population- based cohort study conducted in Israel showed that 5 Mpox infections \noccurred among subjects vaccinated with 1 subcutaneous dose and 16 infections occurred \namong unvaccinated subjects. The VE for Dose 1 was calculated as 86% with the confidence \ninterval of 59 % to 95%. A nationwide US case -control study with a 1:4 ratio of cases matched to \ncontrols had an adjusted VE of 35.8% with a 95% confidence interval of 22.1% to 47.1% for 1 \ndose and 66% with a 95% confidence interval of 47.7% to 78.1% for 2 doses, regardless of the \nvaccination route. In terms of p opulation- based adjusted measures of VE using case -control \nstudies , a case- control study of adult MSM 18─49 years of age in 12 US jurisdictions had an \nadjusted VE of 76% with a confidence interval of 48% to 89% for the 2 doses. Those are interim \nresults. This study is ongoing, so the WG hopes to have more information to present during the \nJune 2023 ACIP meeting. Unpublished preliminary results from a NYS case -control study of \nadult male Mpox cases matched to STI controls had an adjusted VE of 68% with a confidence \ninterval of 25 % to 86% for 1 dose and 89% with a confidence interval of 44 % to 98% for 2 \ndoses. These also are preliminary results and the analyses are ongoing. \n24 \n \n   \n      \n   \n        \n  \n     \n    \n  \n    \n     \n   \n \n  \n     \n    \n   \n  \n   \n    \n    \n   \n  \n \n      \n   \n     \n    \n      \n  \n    \n  \n  \n     \n      \n   \n     \n     \n    \n \n \n   \n    \n     \n       \n      \n    \n   \n   \n In terms of PEP effectiveness and infections following a single JYNNEOS dose \n10% (11 out of 108 subjects ) in France who were administered JYNNEOS after Mpox exposure \nbecame symptomatic with Mpox disease soon after vaccination. The interquartile range was 1 \nto 6 days, with a median of 5 days . Notably, the clinical course was mild among those persons. \nAlso in France, there was an observational study involving people who received a single \nsubcutaneous dose. In this study , 4% were infected during the month after the vaccination and \nnone had serious infection. In a NYC cohort study of individuals with high- risk exposure , VE was \n77% with PEP <14 days after last exposure and 79% with PEP <14 days after the first \nexposure. B ased on all of this information that seemed to support the benefits of the vaccine, \nthe WG’s interpretation was that the desirable anticipated effects of Mpox vaccine during an \noutbreak are large. \nVaccine safety is focused on the subcutaneous route of administration during May 22, 2022 \nthrough January 13, 2023. A total of 1,125,168 JYNNEOS vaccine doses were administered. \nCDC monitored JYNNEOS safety using VAERS and VSD for vaccine recipients of all ages. The \nmost common AEs reported were non- serious and included injection site reactions consistent \nwith pre -licens ure studies. These were reported at similar rates for doses received by \nintradermal and subcutaneous administration and SAEs were rare among adults. The WG’s \ninterpretation is that the undesirable anticipated effects of Mpox vaccine during an outbreak are \nsmall. The WG’s interpretation of the balance between the desirable and undesirable effects \nwas that the desirable effects outweigh the undesirable effects and favored the intervention of \nvaccination with JYNNEOS. \nRegarding the Values domain, surveys have been used to assess the values of the individuals \nwho are being vaccinated during the 2022 outbreak. Even though this vote is for Mpox \noutbreaks in general that may not be specific to male- to-male sexual contact, there are data \nfrom this outbr eak to rely on to answer this question. In terms of populations at highest risk of \nMpox, and August AMIS survey found that 53.1% of respondents had concerns about getting \nMpox. During October ─December, an AMIS survey showed that those with high Mpox concer n \nhad a 3.5 times odds of being vaccinated. Interest in the vaccine seemed to be high during \nAugust ─November when greater than 85% of respondents in the AMETHYST study were \ninterested in the vaccine. During August ─December, 50% of Porter Novelli survey res ponders \nwho identified as LGBTQ+ felt that the vaccination is important to protect from Mpox. That \nincludes not only MSM, but also other LGBTQ. During October ─November, greater than 70% of \nMSM in a San Francisco survey of persons experiencing homelessness reported that they \nwould accept or have accepted vaccination. This is important because a disparity has been \nobserved in that individuals experiencing homelessness have experienced a disproportionate \nnumber of cases just as those who are B lack and Hispanic have. The WG’s interpretation was \nthat the target population probably feels that the desirable effects are large relative to the \nundesirable effects . \nThere is some uncertainty or variability in how many people might value the vaccination. During \nthe 2022 Mpox outbreak, willingness to be vaccinated was dynamic and depended upon \nperceived vulnerabilities. Clear demand for JYNNEOS vaccination occurred, but many still \nremain unvaccinated for unclear reasons. The demographics of future outbreaks also would be \nunclear, which is why the WG believes there might be some uncertainty or variability. It is \nunknown what the demographics of future outbreaks might be , who the affected populations \nmight be, and whether the values expressed by the population most affected by the 2022 Mpox \noutbreak can be extrapolated to all other populations. For this reason, the WG’s interpretation \nwas that there is possibly important uncertainty or variability. \n25 \n \n     \n   \n      \n  \n    \n     \n    \n  \n \n   \n    \n    \n      \n    \n \n    \n  \n    \n    \n   \n \n      \n   \n      \n \n  \n      \n    \n     \n  \n \n   \n   \n  \n   \n    \n     \n  \n     \n \n     \n   \n    \n   \n     \n  \n  \n   \n \n      \n    Moving to the Acceptability domain, stakeholder perceptions are very important to this question. \nSermo is an online community of greater than 1.3 million clinicians. During July 31─ August 1, \n2022, survey results of US clinicians (n=415)  showed that 69% felt that the US was without \nenough Mpox vaccine to handle the outbreak, indicating that they wanted vaccine to be \navailable. A September 12, 2022 survey among 62 US clinicians showed that 66% had treated \nat least 1 Mpox patient, 76% knew where a patient could get JYNNEOS vaccination, and 86% \nwanted to be able to prov ide vaccination to their office. Taken together, the WG interpreted this \nas the clinician stakeholders being supportive of vaccination. \nIn terms of health departments and CBOs, h ealth departments have been requesting JYNNEOS \nand organizing vaccination campaigns. Approximately 70% of the allotted JYNNEOS vaccine \ndoses already have been requested and shipped to states in response to requests from \nstakeholders. In addition, the VEPP has enabled jurisdictions to request more than their allotted \namount of JYNNEOS vaccine. It was established to support innovative ways to address \nvaccination disparities, encourage vaccination coordination between health departments and \nCBOs, and promote innovation to strengthen existing vaccination infrastructure. A total of 28 \nprograms involving 15 jurisdictions and approximately 25,000 doses have been associated with the VEPP. This is above and beyond the initially allotted amounts, all of which illustrates that \nthere seems to be support among stakeholders, health departments, and CBOs . The WG’s \ninterpretation is that the intervention is acceptable to key stakeholders . \nRegarding the R esource Use domain, JYNNEOS vaccine is provided from the HHS SNS free of \ncharge. Vaccines are a good use of resources during an outbr eak and this E tR and ACIP vote \nare intended for any outbreaks. However, there are costs and challenges associated with \nmobile pop- up vaccination sites . A cost- effectiveness analysis of vaccine implementation during \nthe current outbreak is not currently ava ilable. As comments during previous sessions have \nindicated, use of the SNS is sometimes not as efficient as would be preferred. The WG was split \non their interpretation of whether the intervention is a reasonable and efficient allocation of \nresources.  Some WG members felt that it was reasonable, but that the efficient element was \nuncertain. Therefore, the interpretation was that it varies. \nWith respect to the Equity domain, no groups or settings are disadvantaged by a \nrecommendation for JYNNEOS use during Mpox outbreaks. Effectiveness is the same for all \nimmunocompetent persons. Implementation to assure equitable access will be important, \nparticularly among persons who are at high risk for severe outcomes. This recommendation by \nACIP might facilitate broad acceptance of the vaccine (e.g., by insurance companies and health \ndepartments ) because it is an endorsement by ACIP after rigorous review of the evidence. The \nWG’s interpretation was that interpreting equity as independent of implementation challenges, \nthe impact on health equity is that equity probably would be increased. \nIn terms of the F easibility domain, the feasibility of conducting vaccine campaigns in \ncommunities , at events , and within the public health facilit ies was demonstrated in 2022. \nVaccinations can be integrated into provider ’ practices . Standing orders are available, the IIS \nrequirements for reporting vaccinations are the same as for COVID -19 vaccines, and JYNNEOS \ncan be stored refrigerated for 8 weeks. A wide range of vaccinators can administer JYNNEOS \nunlike the other orthopoxvirus vaccine, which some clinicians are hesitant to administer . All of \nthese elements support the feasibility of vaccines and the vaccine recommendation. which some clinicians ar e hesitant to administer. The WG thought carefully about this and felt \nthat the JYNNEOS vaccination probably is sustainable during outbreaks. Vaccine access is an important concern. There needs to be increased , convenient , and low stigma access for all \npersons  who might be at risk . Considerations to ensure vaccine equity include strong ties with \n26 \n \n    \n    \n \n \n   \n    \n     \n     \n   \n   \n    \n    \n    \n \n    \n  \n \n \n    \n     \n \n \n \n \n     \n     \n \n   \n \n     \n \n \n   \n     \n       \n      \n   \n   \n      \n   \n  \n     \n \n    \n \n  \n  \n \n \n \n  \n CBOs , support for vaccination events, engagement of trusted messengers, and ensuring that \nthere is access, including in rural areas. The WG’s interpretation was that the intervention is \nfeasible to implement. \nTo summarize the responses to all of the E tR questions, the WG felt that there was possibly \nimportant uncertainty or variability, mostly because they did not have data about stakeholders \nwho might be affected d uring other types of Mpox outbreaks. The WG felt that it is reasonable to \nhave vaccines during an outbreak if it would prevent infections, which the Mpox vaccine does. \nThere was some concern about whether use of this intervention is an efficient allocation of \nresources , so the WG’s interpretation of whether the intervention is reasonable and efficient \nallocation of resources is that this varies . In terms of the balance of consequences, the WG felt \nthat the desirable consequences clearly outweigh the undesirable consequences in most \nsettings and drafted the following proposed recommendation language for ACIP’s consideration: \nACIP recommends the 2-dose* JYNNEOS vaccine series for persons aged 18 years and \nolder at risk of Mpox during an Mpox outbreak? § \n*Dose 2 administered 1 month after Dose 1 \n§Public health authorities will determine whether there is an Mpox outbreak; a single case may be considered an Mpox \noutbreak at the discretion of public health authorities. Other circumstances in which a public health response may be \nindicated include ongoing risk of introduction of Mpox into a community due to disease activity in another geographic area. \nThe WG also proposed the following Clinical Considerations : \nIn an outbreak setting, vaccine is ideally given pre- exposure but may also be given as post -\nexposure prophylaxis (PEP) , although evidence has not been reviewed by ACIP for PEP at \nthis time. \nThe complete 2- dose vaccine series should be given regardless of the timing of the \nexposure. \nAlthough ACIP has not reviewed the evidence, if there are vaccine supply shortages, the \nintradermal route of administration can be used. \nThe WG will be talking more about data for the intradermal route of administration during the \nJune ACIP meeting. The entire outbreak language from this meeting and the June meeting will \nbe consolidated into one MMWR after that. During the June ACIP meeting, the WG will provide \nupdates about VE and safety and will propose a separate vote for administration of the \nJYNNEOS vaccine in people less than the age of 18 years. The focus during this meeting was \non persons ≥18 years partly because that is simply an expansion of the 2022 ACIP \nrecommendations for persons at occupational risk. It is the same age range, but for a different \ngroup of people. Depending upon the epidemiology of this outbreak, if cases are continuing to \noccur in large numbers, there will be more discussion and consideration for a longer -term \nvaccination strategy with the 2- dose JYNNEOS series during the October 2023 ACIP meeting . \nACIP Discussion Points, Observations , Suggestions on Mpox Vaccine \nFollowing Dr. Ellington’s Presentation \n• It would be beneficial to have additional details on the individual who had a spontaneous \nabortion. \nFollowing Dr. Chard’s Presentation \n• Concern was expressed about the large difference in the estimates of single dose coverage. \n27 \n \n    \n \n    \n  \n   \n  \n \n   \n   \n   \n   \n   \n \n \n    \n  \n    \n  \n   \n    \n \n   \n   \n   \n  \n \n   \n  \n  \n \n   \n  \n  \n   \n  \n  \n \n  \n    \n  \n  \n \n    \n  \n   \n   \n   \n   \n  • It would be beneficial to have information about whether delivering vaccine too deeply \naffects VE. \n• Concern was expressed about very few people being able to administer intradermal vaccine anymore. Dr. Rao emphasized that early on the intradermal route was recommended due to the shortage of vaccine. There is more vaccine available now and route of administration should not be a reason someone is not vaccinated. \n• In the future, it would be helpful to share VE estimates of people with different organ transplants taking different pharmaceutical medications and HIV diagnosis codes . \n• As more information is collected on intradermal versus subcutaneous administration, it would be useful, if possible, to look at that combined with full versus partial vaccination \nto understand if there is any differential impact in the setting of an outbreak if there is a preference for one or the other. \nFollowing Dr. Duffy’s Presentation \n• While it is reassuring that the rate of myocarditis/pericarditis is lower than following Dryvax, the numbers of people vaccinated are still very small. \n• In response to a request for the benefit of the public to explain what it means to have an absence of wheal without vaccine leakage, Dr. Buffy indicated that with intradermal administration, the idea is that there will be a wheal or small area where the skin is \nraised after an injection. Some people have reported to VAERS that when they have \nattempted intradermal administration but have not seen a wheal forming. That is why \nCDC issued some guidance to indicate that just because the wheal is not seen does not \nmean that the intradermal vaccination was not successful. \n• This is another example that reveals that the US has a multifaceted safety surveillance system in which each platform complements the other in terms of strengths and limitations. \n• Though v -safe\nsm had low uptake for Mpox, with the understanding that this likely was a \ntiming issue, it is laudable that CDC plans to use this system in the future for other types \nof vaccines and that in non- emergency response and routine vaccination programs, it is \nexpected to be available early in the launch of new vaccines. \n• It would be beneficial to have information on JYNNEOS vaccine in pregnancy. Dr. Buffy \nindicated that v -safesm has a question about pregnancy. \n• Monitoring vaccine safety in general in pregnancy and among immunocompromised \npersons is crucial. The lessons learned from COVID -19 in terms of these populations \nhave been very positive and reassuring, which is extremely helpful in terms of communication efforts. \nFollowing Dr. Delaney’s Presentation \n• Regarding a question about what types of practices were involved in the Sermo cross -\nsectional surveys, Dr. Delaney indicated that most clinicians surveyed were from primary care or infectious disease practices. In terms of geography and racial distribution, they \nwere primarily in the Northeast. The survey was quick and was open for only about 48 \nhours. The follow -up survey included a more diverse pool of respondents from the US. \nThe data are available online. \n• Looking at safety data, efficacy data, and outreach is a good approach in general in \nterms of how ACIP views a theoretical upcoming vote on this vaccine. \n• It would be beneficial to hear more about the reason African Americans had the highest rate of vaccine uptake at the beginning but the lowest rate as time progressed in terms \nof whether it was related more to access or lessening interest in the vaccine. Dr. \n28 \n \n   \n   \n    \n   \n   \n    \n  \n    \n  \n  \n  \n   \n  \n  \n  \n    \n \n   \n   \n   \n \n    \n \n  \n \n \n   \n \n  \n   \n      \n \n    \n  \n \n  \n    \n \n     \n  \n   \n    \n    \n  \n \n   \n     \n Delaney noted that the AMETHYST questions could unpack that more, though intention \nto get vaccine has not yet been assessed by race and ethnicity . \n• It seems that more education is needed to make at risk populations aware of the \nproblem, given that the target populations do not know much about the vaccine and/or \nMpox disease. Dr. Delaney acknowledged that the AMETHYST and AMIS cohorts \nshowed that there were gaps in knowledge, so CDC adapted its messaging based on \nthose early survey results to be more sex -positive and to ensure that the vaccine was \nbeing talked about as a sexual health intervention, because most of the places where \nthe vaccine was available outside of the health equity events were STI and PrEP clinics and HIV care sites. The Community Engagement Task Force developed the materials \nand the social media marketing and worked with CDC’s community partners to get the \nmessage out to the most affected communities. He agreed that more needs to be done. \n• The difference between the number of people who are interested in the vaccine and the \nnumber who actually have taken the vaccine is striking. That disconnect suggests that there is creative work to be done. \n• One approach to address the equity issue is positive deviance; that is, highlight successes and figure out how to learn from them. \n• From a local public health standpoint, the aspect of achieving equity is often a matter of having adequate resources for local public health and their partners to conduct effective outreach to those who are at higher risk. ACIP’s guidance and identification of potential \nequity issues can help to direct resources accordingly . \n• Equity always has been increased in terms of pediatric vaccines because of the \nVaccines for Children Program (VFC). Because there is not a comparable program for adult vaccines, barriers can increase equity among adult populations. \nFollowing Dr. Carter’s Presentation \n• The launch of this response was very difficult because the vaccine distribution system was totally different from what all of the public health immunization programs had been utilizing beforehand. In terms of the issue of equity, states were only allowed to have 5 \nsites receive vaccine. That is one of the reasons why there was such limited distribution \nof the vaccine. If the SNS is going to be used via ASPR, consideration must be given to \nthe efficiency of that distribution system. \n• This presentation highlighted the complexity of the response and how many people were involved, both on the frontline and behind the scenes. The data with doses by month addressed the equity issue and demonstrated clearly that the concerted efforts were \neffective. All jurisdiction s should be encouraged to look at their data in a similar way . \n• Immunization registry reporting is critical to determine what doses have been given and \nto avoid errors. \n• The lessons learned from Mpox should be applied to other outbreaks to inform quick mobil ization versus spending months gearing up for an unexpected outbreak. \n• It would be nice to have an overall statement saying that ACIP does not recommend routine HCP vaccination for frontline workers, along with more guidance about when \nPEP should be offered to frontline HCP who perhaps were not using personal protective \nequipment (PPE) and later finds out a patient has Mpox.  Dr. Carter indicated that CDC \nworked closely with its Healthcare Worker Task Force and NIOSH colleagues to review \nthis carefully and the conclusion was that PPE recommendations provided adequate \nprotection against the risk of Mpox transmission and therefore, JYNNEOS vaccine was \nnot recommended for HCP. Certainly, someone who is exposed to Mpox who was not \nadequately protected could be off ered PEP. \n29 \n \n   \n \n \n  \n  \n   \n \n \n   \n \n \n       \n     \n   \n  \n   \n   \n   \n  \n  \n   \n   \n   \n   \n    \n  \n    \n \n   \n \n  \n  \n  \n \n  \n \n      \n  \n    \n  • It would be beneficial to continue to have the flexibility to offer either the intradermal or \nsubcutaneous route of administration, especially since intradermal can be stigmatizing. \nFollowing Dr. Rao’s Presentation \n• Looking at the entire picture, this is a common disease. Even now at its lowest, there are still 2 cases per week. That is higher than the number of cases per week in the past few \nyears, and there is a fairly high death rate. There is a very effective vaccine with good \ndata. \n• It was observed that case counts also have decreased in many countries where no \nvaccine is available. While vaccine is certainly playing a role, behavioral changes also \nmay be having an impact. \n• Significant information is still lacking for immunocompromised patients. In general, it \nseems that immunocompromised patients need additional doses. Perhaps during the \nOctober ACIP meeting, consideration can be given to additional doses of JYNNEOS for \nimmunocompromised patients . Dr. Rao indicated that CDC is collaborating with other \npartners to try to conduct some immunogenicity studies to better understand the role of \nJYNNEOS for immunocompromised patients and plans to discuss this with the WG. \nClinicians on the WG have raised this concern for HIV, immunocompromised, t ransplant, \nand other patients who have higher risk. \n• Concern was expressed that having a risk -based recommendation could limit access, be \nstigmatizing to some extent, and present inherent challenges for future Mpox outbreaks \nor other infectious diseases wit h similar characteristics. While education will help, it will \nnot solve the problem to the extent that someone who is not aware they are at risk needs to be seen in a clinical setting and that their risk needs to be assessed. CDC and \nthe WG emphasized that the ICC explains that individuals should not have to explain \ntheir rationale for wanting to be vaccinated and that there is a need for continual community engagement and education to keep Mpox in the public eye. \n• It will be important for longer -term recommendations and the ICC to address booster \ndosing, which will be part of the WG’s discussion after June 2023. \n• The question often arises about whether someone who recovered from Mpox should be vaccinated, which the WG is not currently recommending because it is believed that \nthese individuals will have protection from their natural illness. There are booster studies \nunderway that will inform booster dosing recommendations in the coming years. \n• There can be complicated political considerations in declaring an outbreak. The proposed recommendation language is broad and as such offers the flexibility to \nimplement more aggressive vaccination measures if state and local health departments \nfeel that is needed. \n• It is impressive that over 90% accurate data were captured on race and ethnicity . It \nwould be great to capture that information and information on disabilities in all clinical \ntrials and other studies in order to inform and enhance access. \n30 \n \n   \n \n        \n  \n \n    \n   \n \n \n    \n   \n \n \n \n \n  \n \n    \n    \n  \n \n             \n   \n         \n        \n \n \n \n \n \n     \n     \n   \n     \n   \n   \n    \n     \n   \n   \n   \n   \n \n     \n   \n    \n    \n   \n    \n      \n   Vote: Mpox Vaccine \nAgam Rao, MD (CDC/NCEZID) displayed and read the proposed vote language following the \npublic comment period. The vote was combined with the Mpox session for ease of reading : \nACIP recommends the2- dose* JYNNEOS vaccine series for persons aged 18 years and \nolder at risk of Mpox during an Mpox outbreak? § \n*Dose 2 administered 1 month after Dose 1 \n§Public health authorities will determine whether there is an Mpox outbreak; a single case may be considered an Mpox \noutbreak at the discretion of public health authorities. Other circumstances in which a public health response may be indicated include ongoing risk of introduction of Mpox into a community due to disease activity in another geographic area. \nMotion/Vote: Mpox Vaccine \nDr. Loehr made a motion to approve the recommendation as stated, which Dr. Poehling \nseconded. No COIs were declared. The motion carried with 14 affirmative votes, 0 negative \nvotes, and 0 abstentions. The disposition of the vote was as follows: \n14 Favored: Bahta, Bell, Brooks, Chen, Cineas, Daley, Kotton, Lee, Loehr, Long, McNally, \nPoehling, Sanchez, Talbot \n0 Opposed: N/A \n0 Abstained: N/A \nRESPIRATORY DISEASE SURGE, FALL 2022, UNITED STATES \nJosé R. Romero, MD (CDC, Director NCIRD) emphasized that it was a pleasure to speak to \nACIP in his role as Director of NCIRD. Having previously served as a member and the C hair of \nthe CDC’s ACIP, he truly understands and greatly appreciate s the time and effort required by its \nmembers to convene a meeting of the ACIP. He observed that o ver the course of the meeting, \nthe committee would hear presentations on influenza and COVID -19 vaccines , as well as novel \nRSV vaccines. To set the scene for the next few sessions, he wanted to give a brief overview of \nthe co -circulating respiratory viruses that are observed over the W inter and F all and highlight \nhow they are of critical importance in terms of vaccination. This past Fall and Winter, the US \nsaw high co- circulation of respiratory syncytial virus (RSV), influenza virus, and SARS -CoV-2. \nThes e put significant stress on healthcare systems and the drug supply chain. After a brief and \nanticipated uptick of hospitalizations and cases around the holidays, there is now a continued \ndecrease in COVID, influenza, and RSV cases and hospitalizations nati onally. \nFor those who are not pediatricians, he explained that RSV is a well- recognized respiratory \npathogen of infants and a common cause of respiratory disease in older adults. In adults, RSV \ncan be difficult to differentiate from COVID -19 and influenza based on symptoms alone and is \nfrequently overlooked as a diagnosis for viral respiratory disease in adults. In the elderly or in \nthose with certain comorbid conditions, RSV infections can be significant and life- threatening. \nTypically, adults experience mild cold- like symptoms, although some can develop a lower \nrespiratory tract infection (LRTI) such as pneumonia. Older adults, adults with chronic heart and \nlung conditions or diseases , and those with weakened immune systems are at higher risk for \n31 \n \n       \n     \n   \n     \n  \n  \n     \n    \n   \n \n    \n       \n     \n     \n   \n  \n \n   \n    \n     \n    \n    \n     \n      \n      \n \n     \n  \n   \n      \n    \n   \n     \n   \n \n   \n   \n \n    \n      \n   \n     \n      \n   \n  severe RSV infections. RSV is also known to lead to worsening of chronic conditions common in \nadults, such as asthma, congestive heart failure, and chronic obstructive pulmonary disease \n(COPD) . Each year in the US , it is estimated that between 60,000 and 160,000 hospitalizations \noccur and 6 to 10,000 deaths result in older adults due to RSV infections. This past fall, the \nCDC surveillance team saw an increase in RSV detections, RSV -associated emergency room \ndepartment visits , and hospitalizations, including among older adults. Current national trends for \nRSV activity indicate that it has returned to baseline levels. For seasonal influenza, the activity \ncontinues to decline across the country. While influenza activity is declining, it remains possible \nthat a second wave may occur later in the season as it has in the past. \nCDC has responded to the increase in co- circulating respiratory viruses in multiple ways, but Dr. \nRomero thought the most important way to bring before the ACIP was that in January 2023, \nCDC released 2 new respiratory diseases surveillance dashboards that are accessible to public \nhealth medical professionals and the public in general. The first is th e Respiratory Virus \nHospitalization Surveillance Network (RESP- NET), which is an interactive dashboard that \ndisplays respiratory virus -associated hospitalizations from 3 existing surveillance platforms : \nCoronavirus Disease 2019 (COVID- 19) Hospitalization Surveillance Network (COVID -NET) , \nInfluenza Hospitalization Surveillance Network (FluSurv -NET) , and Respiratory Syncytial Virus \nHospitalization Surveillance Network (RSV-NET). The second dashboard is the National \nEmergency Department Visits for COVID -19, Influenza, and Respiratory Syncytial Virus, which \ndisplays data on emergency room visits for multiple respiratory conditions as tracked by the \nNational Syndromic Surveillance Program (NSSP). This dashboard presents data captured from \napproximately 75% of all emergency departments (EDs) in the US , so it is a very robust \ndatabase. These dashboards allow users to easily see hospitalizations and ED data for these 3 \nviruses by age and track and compare the trends for SARS -CoV-2, influenza, and RSV disease. \nRecent outbreaks highlight the importance of remaining vigilant about prevention. CDC \ncontinues to conduct outreach to clinicians, public health, and school partners and the public to \nraise awareness about the importance of vaccination for COVID -19 and influenza for everyone \n6 months of age and older. Dr. Romero noted that during the first day of this meeting, there \nwould be presentations and discussion on pediatric and maternal RSV vaccines that may \nbecome available for the prevention of RSV -related disease in the near future. Since the \ndetection of the first case of SARS -CoV-2 virus over 3 years ago, more than 1 million \nAmericans, including 2,000 children, have tragically died as a result of COVID -19 infection. \nNearly 6 million individuals have been hospitalized and many more continue to suffer from long-\nCOVID conditions. Fortunately, due t o the rapid development of safe and effective vaccines, the \nposition is very different from 3 years ago. COVID -19 vaccinations have prevented millions of \nsevere illnesses, hospitalizations, and deaths since their introduction in December 2020. Many current members of the ACIP were on the committee at that time. Now 80% of Americans have \nreceived at least 1 dose of the primary COVID -19 vaccine series and over 667 million doses of \nvaccine have been administered. However, despite the introduction of a bivalent booster in \nSeptember 2022 , uptake has been low with only 15% of the US population having received an \nupdated booster. The numbers are even lower for pediatric patients. Vaccinations and antivirals \ncontinue to be the best protection against serious illness for COVID -19. \n32 \n \n  \n   \n   \n   \n        \n    \n   \n  \n      \n   \n   \n      \n       \n    \n \n \n \n  \n     \n      \n   \n  \n    \n  \n       \n  \n   \n    \n      \n    \n     \n  \n \n    \n   \n       \n    \n  \n  \n \n \n    \n        \n    \n  \n \n     \n    \n    \n \n  Unfortunately, during the COVID -19 pandemic, there was a concerning decrease in routine \nimmunizations for both adults and children. Routine vaccinations are rebounding, although \nunevenly , and have yet to fully recover in all groups. A significant and extremely concerning \nexample is that the percentage of uninsured children not vaccinated by their second birthday \nwas recently found to be 8 times that of privately insured children. That is even in the context of \nVFC, a program that is designed to address these inequities in healthcare insurance. While \ncontinuing to investigate the impact of the pandemic on routine immunizations, it is imperative to \ntake steps to help get everyone back on track with their routine immunizations. Everyone must \ncontinue to work together to improve vaccination coverage by reduc ing barriers, increas ing \naccess, and strengthening vaccine confidence. For influenza and COVID- 19, safe , effective, \nlicensed or authorized vaccines are currently available for the prevention of serious disease. It is \nvery possible that in the not-too-distant future , Americans also may have options for the \nprevention of a third respiratory virus, RSV. With that, Dr. Romero thanked ACIP and wished \nthem good luck with t heir deliberations and discussions. \nDiscussion Points \nBefore opening the floor for discussion, Dr. Lee emphasized Dr. Romero ’s key points. First, \ncontext is everything. Many f amilies with children and/ or older adult members have had multiple \nrespiratory viral illnesses this Winter. On top of that, pediatric providers had such a significant \nrespiratory surge during a certain period of time, all due to multiple respiratory illness es, they \nhad to divert and redirect many of the children who were very ill and needed care. There also \nwere other children who needed to come in for other reasons. This has had a major impact on \nthe healthcare delivery system and families. One reason the ACIP was so grateful to Dr. \nRomero for being willing to speak about this context was that for the first time in a long time, \nACIP had the opportunity during this meeting to review data on influenza vaccines, RSV , \nCOVID -19, and pneumococcal vaccines. All of those are important preventive measures for \nACIP to consider as part of a potential respiratory disease prevention platform. While they would \ntake each of these vaccines into consideration on an individual basis, it also is important to think \nthrough the broader implementation context for young children and older adults to ensure that \nas the committee is m aking these recommendations, they also are thinking ahead about how \nthese programs would be deployed in the various populations. \nIn response to Dr. Loehr ’s request to speak further to Dr. Romero’s revelation that the \npercentage of uninsured children not vaccinated by their second birthday was recently found to \nbe 8 times that of privately insured children , Dr. Romero said that given that the VFC was in \nplace and functioning well pre- pandemic, this suggests a major problem. The VFC was \nestablished to address barriers in access, yet this problem of lower vaccine rates has been particularly severe among racial and ethnic populations, rural areas, and areas experiencing \npoverty. \nDr. Talbot expressed excitement about viral vaccines coming online for older adults , but \nlamented how complicated vaccines are for adults over 65 years of age because of Medicare. \nShe asked whether any processes are in the work s to streamline vaccines under Medicare Part \nB so that physicians can vaccines while patients are in the clinic . \nDr. Wharton indicated that there have been some changes in policy with recent legislation. She \ncalled upon Mary Beth Hance to make some brief co mments about the changes to Medicare \nvaccine reimbursement issues under Medicare Part B and D from the Inflation Reduction Act \n(IRA). \n33 \n \n       \n   \n   \n    \n    \n  \n \n       \n       \n    \n       \n   \n \n       \n \n  \n \n   \n   \n \n   \n \n  \n   \n \n \n       \n     \n \n \n    \n      \n \n     \n     \n    \n  \n  \n      \n  \n    \n   \n      \n    \n  Mary Beth Hance (HRSA) indicated that the IRA made changes to coverage of vaccines for \nadults in Medicare . COVID -19 was added as a Part B covered vaccine. For P art D, there is no \ncost sharing for patients . Covered Part B vaccines now include influenza , pneumococcal, \nhepatitis B for individuals at high and intermediate risk , COVID -19 vaccines , and vaccines that \nare reasonable and necessary to treat an injury or exposure to a disease. There is coverage of \nACIP -recommended vaccines with no cost -sharing under Part D . \nDr. Romero added that while this benefit s those with insurance, there is still a large population \nof adults in the US who do not have insurance. Serious consideration of a program that would \noffer vaccine to those individuals, a Vaccines for Adults (V FA) modelled in some way after the \nVFC, is something the American public needs to consider moving forwar d in order to catch all \nAmericans up on vaccinations and make these vaccinations available to all. \nDr. Daley asked what is known about vaccination rates for adults without insurance and if there \nis a comparable figure for influenza or COVID vaccination, a nd what would be required to \nestablish a VFA program. \nDr. Romero indicated that he could share specific data during the Agency Update session, but \nthat rates are substantially lower for those who are uninsured. Even a co -pay can be a deterrent \nto accessin g vaccines. Establishment of a VFA would need to be appropriated for within the \nPresident ’s Budget and legislated by Congress. \nDr. Goldman (ACP) asked whether it would be within CDC’s purview to handle certain state \njurisdictions deliberately spreading disinformation regarding the safety and efficacy of the \nvaccines . \nDr. Romero responded that CDC, as always, is engaged with educating the public and providing information that is scientifically correct and sound. It is not within the realm of C DC to actively \ninvolve itself within jurisdictions. Simply put, these are decisions made by the jurisdiction or \njurisdictions involved. \nDr. Hogue (APhA) said he was struck by the inequities that still exist in US society and \nemphasized that they should all do what they could to address them. He reported that America's \npharmacies are having significant issues with the Part D plans and the inconsistency with which \nthe Part D plans cover the administration of vaccines. They treat vaccines as drugs because \nthey have a National Drug Code ( NDC) number, but many of the Part D plans either try to \nbundle the administration fee with the vaccine for administration simplification or they pay very \nlittle or no administration fee at all. His concern is that during the pandemic , people have \nbecome quite dependent upon community -based pharmacies to improve access points, \nespecially in rural areas of the country. If the Part D plans are not held to account by CMS to \nconsistently pay a meaningful administration fee and stop clawback s, which are very common in \nthe pharmacy world for drugs, it could result in a situation of pharmacies being unable to offer \nvaccines for Medicare beneficiaries under the Part D plan in the future. Therefore, he wanted to \nraise this awareness and an alarm bell so that colleagues at CMS would work with them to try to \ncorrect this situation in the coming Part D Call Letter. \n34 \n \n  \n  \n \n \n \n   \n \n \n    \n \n  \n \n      \n    \n  \n \n    \n   \n   \n   \n   \n  \n \n   \n \n \n  \n \n    \n \n     \n  \n    \n   \n \n  \n  \n     \n   \n    \n  \n     \n \n  INFLUENZA VACCINE \nIntroduction \nH. Keipp Talbot, MD, MPH (ACIP, WG Chair) indicated that this session would include \npresentations focused on influenza activity, interim influenza VE against inpatient, ED, and \noutpatient illness in the 2022- 2023 season, interim estimates of 2022- 2023 influenza VE from 2 \nstudies in Wisconsin, and published estimates of live attenuated influenza vaccine (LAIV). \nUS Influenza Activity Update \nLisa Grohskopf MD, MPH (CDC/NCIRD) presented a brief update of the 2022- 2023 US \ninfluenza activity. In terms of virological surveillance data, results of influenza -positive tests are \nreported weekly to CDC from a very large network of clinical and public health laboratories. The \npercent of positive influenza tests is one of the indices of influenza activity. For 2022 -2023, the \npercent of positive tests peaked in late November /early December at about 26%. The percent \npositive has been decreasing for about the 9th consecutive week to 1.7%. The peak of 26% is \nroughly comparable to other recent seasons. However, the peak shifted earlier than is typical. \nThe peak also was higher than the 2 seasons immediately preceding 2022- 2023. The other \ncomponent of this system, Public Health Laboratories (PHLs), provides a sense of the influenza viral types and subtypes in circulation. H3N2 viruses have predominated, although there also \nhas been appreciable co -circulation of H1N1pdm09- like viruses. About 99.4% of the viruses \ncharacterized thus far have been influenza A. Very little influenza B has been seen at this point in the season. \nLaboratory -confirmed influenza- associated hospitalizations come from FluSurv -NET. \nCumulative hospitalizations have leveled off at about 59.5 per 100,000 and have stayed flat in \nrecent weeks. As with the peak shift, influenza -associated hospitalization activity shifted earlier \nin the season as well. Deaths of children associated with laboratory -confirmed influenza has \nbeen reportable in the US since 2004. Thus far, as of the weekend ending February 11, 2023, a \ntotal of 1 11 pediatric deaths have been reported through the Fluview mechanism. This is \nunfortunately more than in 2020- 2021, for which 1 pediatric death was reported and 2021 -2022, \nfor which 45 pediatric deaths were reported. \nTo summarize influenza activity as of the week ending February 11, 2023, US influenza act ivity \nrose early, peaking nationally during late November/early December. The percent that test ed \npositive peaked at about 26% and is currently down to about 1.7%. Influenza A (H3N2 ) virus has \npredominated so far with co- circulation of A(H1NI )pdm09. The cum ulative influenza- associated \nhospitalization rate has leveled in recent weeks to about 59 per 100,000. A total of 111 \ninfluenza- associated pediatric deaths have been reported thus far this season. Overall influenza \nactivity is increased compared with the previous 2 seasons. US influenza activity is currently \nlow. \n35 \n \n      \n \n         \n  \n    \n   \n    \n     \n   \n   \n    \n   \n \n      \n \n \n    \n      \n   \n  \n    \n    \n   \n      \n     \n \n \n     \n   \n   \n     \n       \n \n   \n   \n   \n  \n \n \n   \n   \n \n    \n  Preliminary 2022 -2023 Influenza Vaccine Effectiveness: CDC Networks\nSamantha Olson, MPH; Nathaniel Lewis, PhD; and Mark Tenforde, MD, PhD (CDC/NCIRD) \npresented preliminary 2022- 2023 influenza VE results from 3 CDC networks: New Vaccine \nSurveillance Network (NVSN), Investigating Respiratory Viruses in the Acutely Ill (IVY), and the \nVISION Vaccine Effectiveness Network . Ms. Olson explained that CDC uses these 3 networks \nto evaluate VE against laboratory -confirmed influenza- associated outpatient visits, emergency \ndepartment visits, and hospitalization. Across all 3 networks, the methods are similar. For this \nanalysis, patients were enrolled with acute respi ratory illness (ARI) from Fall 2022 through early \n2023. Each study has a test -negative design comparing vaccination odds among case patients \nwith influenza A confirmed by molecular assay versus control patients testing negative for \ninfluenza and SARS- CoV-2. Vaccination status was defined as the receipt of any 2022 through \n2023 influenza vaccine according to medical records, immunization registries, claims data, \nand/or a self -report. For each analysis, VE was calculated as (1 ─ the adjusted odds ratio) x \n100. \nThe NVSN analysis calculated VE against influenza- associated hospitalizations and ED visits \namong children 6 months through 17 years of age. NVSN conducts active surveillance at 7 sites \nacross the country: Seattle Children’s, Children’s Mercy Hospital Kansas City, Texas Children’s \nHospital Houston, Vanderbilt University Nashville, Cincinnati Children’s, University of Rochester, \nand Children’s Hospital of Pittsburgh. NVSN enrolled inpatient and ED patients 6 months \nthrough 17 years of age with acute respi ratory illness within 10 days of illness onset from \nSeptember 13─January 25 for this analysis . A test-negative design was used in which patients \nwere considered vaccinated if they received at least 1 dose regardless of their age and relied on \nverified vaccination or self -report. Logistic regression was used for this analysis, adjusting for \nsite, age, and calendar time of admission. \nIn terms of preliminary VE estimates against pediatric hospitalizations and emergency \ndepartment visits among children 6 months through 17 years of age. T here were 640 influenza-\npositive cases and 2,256 controls included in this analysis. Nineteen percent of cases versus \n33% of controls received a seasonal influenza vaccine. O verall VE was 49% among inpatients, \nwith a higher -point estimate of 68% observed . Among ED visits, 42% VE was calculated.  When \nstratified by subtype, effectiveness against H3N2 was 45% and against H1N1 was 56%. To \nsummarize, b ased on preliminary estimates for the 2022─2023 influenza season, influenza \nvaccinations significantly reduced laboratory -confirmed medically -attended influenza in children. \nEffectiveness against pediatric hospitalizations was 68%. Effectiveness against pediatric ED \nvisits was 42%, and important protection was observed against both H3N2- and H1N1-\nassociated illness. Dr. Lewis explained that the IVY analysis assessed VE against influenza- associated \nhospitalization among adults ≥18 years of age receiving inpatient medically -attended treatment \nfor influenza. This analysis was drawn specifically from patients at 24 medical centers in 19 \nstates in the IVY network shown in the map below: \n36 \n \n  \n \n \n   \n    \n   \n   \n  \n    \n        \n     \n    \n      \n   \n    \n    \n    \n  \n \n       \n       \n    \n   \n   \n        \n     \n     \n  \n       \n \n \n \n   \n   \n   \n      \n       \n   \n \nThe methods used in IVY are very similar to the NVSN methods. The data rage for the analysis \nwas October 1─January 31, 2023. This analysis used a test -negative case -control method that \nassessed the odds of vaccination among cases versus controls . This analysis was adjusted for \nCensus region, age, sex, race /ethnicity, and month of illness onset. Fairly encouraging results \nwere s een in this analysis of 219 cases who tested positive for influenza and 921 controls who \ntested negative for both influenza and SARS -CoV-2. Vaccination coverage was 31% among \ncases and 43% among controls. Overall, VE was 43% for persons ≥18 years of age. As \nexpected, there was some variation by age group , with lower protection among those ≥65 years \nand older of 35% versus 51% among those 18─ 64 years of age . Importantly, significant \nprotection was observed in the immunocompromised subgroup that was very similar to that of \noverall VE in the network , albeit with a wider and overlapping confidence interval. About two -\nthirds of the 77 specimens analyzed through the end of 2022 were H3N2 and the remaining \nthird were H1N1. The important takeaway is that influenza vaccination significantly reduced \nmedically -attended hospitalized influenza at a VE of 43% . Significant protection was observed in \nthe older adult population and among immunocompromised adults. \nDr. Tenforde present ed preliminary results from the VISION network on influenza VE results \nagainst influenza- associated hospitalizations and ED or urgent care (UC) visits. VISION is an \nelectronic VE network that consists of health systems with integrated laboratory , clinical, and \nvaccination records. The 3 partners contributed data for this analysis, including Kaiser \nPermanente Northern California (KPNC) , Intermountain Healthcare, and HealthPartners in 4 \nstates. For this analysis , encounters included ED or UC visits or hospitalizations between \nOctober 15 ─January 24, 2023 among adults ≥18 years of age w ho received clinical testing for \ninfluenza and had 1 or more ARI -associated discharge codes. Using a test-negative design, VE \nwas estimated by comparing influenza vaccination odds among patients who tested positive for \ninfluenza A versus controls who tested negative for influenza and SARS- CoV-2. VE models \napplied inverse- propensity -to-be-vaccinated weights and adjust ed for potential confounders \nincluding patient age, study site, and calendar time. Preliminary VE estimates against adult ED or UC visits were calculated for 14,011 influenza -\npositive cases and 43,196 influenza- negative controls included in t his analysis. Twenty -three \npercent of cases versus 36% of controls had received a 2022- 2023 seasonal influenza vaccine. \nOverall VE was 44% in all adults ≥18 years of age, including 46% in adults 18─64 years and \n39% in adults ≥65 years of age. A lower point estimate of 30% was seen among adults with \nimmunocompromising conditions. In terms of VE estimates against adult hospitalizations , the \nanalysis included 1,760 influenza- positive cases and 9,377 influenza- negative controls. Thirty -\n37 \n \n    \n       \n   \n \n   \n  \n   \n    \n     \n    \n   \n  \n \n    \n \n  \n    \n \n \n   \n \n       \n     \n    \n      \n   \n    \n   \n   \n    \n   \n \n  \n       \n  \n     \n      \n  \n   \n  \n     \n       \n   \n \n    \n  \n     \n  \n  \n    \n      eight percent of cases versus 49% of controls had received a seasonal influenza vaccine. \nOverall VE was 39% , including 29% in adults 18─ 64 years of age and 42% in adults ≥65 years \nof age . VE was 31% among adults with immunocompromising conditions. \nIn summary, through almost the end of January 2023, influenza vaccinations significantly reduced laboratory -confirmed medically -attended influenza with an estimated VE of 39% \nagainst adult hospitalizations and 44% against adult ED or UC visits. Effectiveness was \nobserved across all age groups and in those with immunocompromising conditions. These \nestimates were higher than VISION Network VE estimates against hospitalization and ED or UC \nvisits from the same sites during the prior 2021-2022 season when mostly vaccine mismatched \nH3N2 v iruses were circulating. A limitation of this analysis was a lack of data to estimate VE by \ninfluenza A subtype including H1 and H3 viruses. \nIn conclusion, across 3 influenza VE platforms, very consistent influenza VE was observed \nduring the early 2022- 2023 influenza season. Vaccination provided substantial protection \nagainst inpatient ED and outpatient illness across all ages. Influenza vaccination also provided \nsubstantial protection among important high- risk groups , including older adults and those with \nimmunocompromising conditions. \nPreliminary 2022 -2023 Influenza Vaccine Effectiveness: Wisconsin \nHuong McLean PhD, MPH (Marshfield Clinic Research Institute) presenting interim \nestimates of influenza VE from 2 studies in Wisconsin: A test- negative case-control study \nfunded by CSL Seqirus and a community cohort study funded by CDC. The methods of the test -\nnegative case -control study are similar to what was presented for the 3 CDC networks , except \nthat the enrollees are outpatients who presented for COVID -19 testing aged 6 months through \n64 years with ARI with a cough of ≤7 days duration. Data presented are from enrollments from \nDecember 2, 2022 through February 10, 2023. Influenza vaccination was defined as \ndocumentation in the patient ’s health record of current season influenza vaccine receipt ≥14 \ndays before illness onset according to the ACIP recommendations. VE estimates were adjusted \nfor age, month of illness onset, and presence of high- risk co nditions. \nInfluenza positive RT -PCR results were highest at the beginning of the enrollment period in \nDecember and have declined since. Of the viruses, 73% were A(H3N2 ) and 26% \nA(H1N1pdm09). All of the 43 characterized viruses were genetically similar to the vaccine \ncomponents. A total of 545 patients with medically -attended ARI were included in this analysis. \nAmong participants, 34% were vaccinated , of whom the majority (84%) received cell-culture \nbased vaccine (ccIIV4). The percentage vaccinated differed by sex, high-risk conditions, and \nCOVID -19 vaccination status. Among the 116 participants positive for influenza, 22% were \nvaccinated compared to 37% of 429 participants who tested negative for influenza and SARS -\nCoV-2. The adjusted VE against outpatient medically -attended influenza A was 54% , with a \n95% confidence interval of 23 % to 73%. VE against influenza A(H3N2 ) viruses was 60% , with a \n95% confidence interval of 25% to 79%. \nThe prospective community cohort study is an ongoing study in Central Wisconsin of 241 \nchildren who have been followed weekly since September 5, 2022. Each week, children or their \nguardians report the absence or presence of the following symptoms over the past 7 days : \nfever, cough, loss of smell or taste, sore throat, muscle or body aches, shortness of breath, \ndiarrhea, nasal congestion or runny nose, or nausea or vomiting. New symptom onset prompts \nself-or guardian- collection of anterior nasal swab for influenza and SARS- CoV-2 research \ntesting. Other relevant information collected from surveys and extracted from EHRs includ e \n38 \n \n     \n   \n    \n    \n    \n  \n \n    \n     \n  \n     \n     \n   \n \n \n  \n    \n     \n    \n    \n   \n     \n  \n   \n  \n \n    \n      \n       \n       \n  \n     \n \n \n \n    \n  \n   \n  \n     \n  \n \n \n \n      \n    \n   \n    \n    \n  vaccination history and clinic influenza test results. To estimate VE against symptomatic \ninfluenza infection in the cohort, a Cox proportional hazards model was used with time -varying \nvaccination st atus. The at -risk window began October 23 , 2022 (7 days before the first case \nwas identified) and ended February 10 , 2023 (positive influenza infection date)—whichever \noccurred first. Vaccinated person time began ≥14 days after receipt of the influenza vaccine. \nUnvaccinated person- time was the time before receipt of influenza vaccine. P erson- time was \ncensored for the 13 days after receipt of influenza vaccine. An influenza case was defined as a \npositive influenza result from a research or clinical test during the at-risk period. V E \neffectiveness was calculated as 1 minus the adjusted hazards ratio x 100% where the hazards \nratios represented the ratio of influenza infections in the vaccinated to unvaccinated person-\ntime. The model adjusted for age, higher at -risk condition, and COVID -19 vacation. Among the \n241 children in the cohort, 39% were vaccinated , of whom 84% received ccIIV4 and 65% \nreceived 2 or more doses of COVID -19 vaccine. A total of 34 (14%) of children were positive for \ninfluenza. \nIn terms of influenza and SARS- CoV-2 infections by week of onset , influenza incidence was \nhighest late November and early December and has declined since. Of the influenza infections, \n85% were caused by A(H3N2 ), 3% were caused by A( H1N1 pdm09) , and the remai ning 12% \nwere influenza A with unknown subtype. The characterized A(H3N2 ) viruses in this population \nwere genetically similar to the vaccine component. Regarding VE against symptomatic influenza \namong children, there were 6 influenza A infections during the 7,292 vaccinated person days of \nfollow- up, resulting in an incidence of 0.82 infections per 1,000 person- days. A total of 28 cases \noccurred during the 15,678 unvaccinated person- days , resulting in an incidence of 1.79 \ninfections per 1,000 person days. VE against symptomatic influenza A virus infection was 71% \nwith a 95% confidence interval in 31% to 90% among children in this cohort. \nThere are several limitations to consider for these studies. First, both studies were conducted in \na single geographic area, Central Wisconsin. However, the virus es that predominated in the \nstudy population was similar to those that predominated across the US. Second, adults ≥65 \nyears of age who generally have lower VE estimates against A(H3N2 ) were excluded. Third, the \nsample sizes were small. This resulted in wide confidence intervals, so it was not possible to estimate VE against A(H1N1 pdm09) or by age groups. Finally, confounding and bias are \nconcerns with observational studies. However, estimates were comparable across the 2 study \ndesigns. \nTo summarize, interim results indicate substantial vaccine- induced protection against influenza \nA during the current season. VE effectiveness was 54% against medically -attended influenza A \nin children and working- age adults and 71% against symptomatic influenza A infection in \nchildren. These estimates are consistent with reported estimates from the 4 CDC networks and \nin Canada and are consistent with a good vaccine match. All characterized viruses from the \nstudy population belong to the same genetic subclade as the viruses included in the 2022- 2023 \nNorthern Hemisphere influenza vaccine. \nUpdate on Published Estimates of LAIV4 Effectiveness: Background \nLisa Grohskopf MD, MPH (CDC/NCIRD) presented a brief update of published estimates of \nlive attenuated influenza vaccine ( LAIV ) effectiveness, noting that these are not CDC data. \nLAIV4, the quadrivalent LAIV, was initially approved in the US in 2012 and came into use during \nthe 2013 -2014 season after having had a trivalent formation available since 2003 in the US. \nLAIV4 was not recommended in the US for use during the 2016- 2017 and 2017- 2018 seasons \nfollowing observation of low effectiveness specifically against H1N1pdm09 -like viruses among \n39 \n \n     \n  \n    \n    \n   \n    \n    \n  \n    \n  \n     \n    \n    \n \n   \n   \n \n      \n    \n     \n     \n    \n          \n      \n      \n    \n     \n    \n      \n \n \n  \n \n   \n     \n   \n    \n     \n     \n  \n  \n  \n  \n  \n     \n    \n \n        \n \n  children 2─17 years of age that was noticed during the 2013- 2014 season and during the 2015 -\n2016 season, both of which had some H1N1 predominance. It was not clear what was going on \nwhen this first was noticed. The 2013- 2014 season was the first H1N1 -predominant season that \nhad occurred since the 2009 influenza pandemic.  It also was the first season the quadrivalent \nproduct was available. However, subsequent studies suggested decreased replicat ive fitness of \nthe LAIV4 H1N1pdm09 -like vaccine virus . Live virus vaccine such as this requires replication of \nthe virus in the nasopharyngeal mucosa in order to be effective. Following those studies, the \nvaccine virus was updated and replaced in the vaccine. LAIV4 was again a recommended \noption in the US starting in 2018- 2019 after a discussion of 3 streams of data during the \nFebruary 2018 ACIP meeting. These included a combined US individual patient level VE analysis that consisted of data from several US sources , a systematic review of post -2009 US \nand non- US LAIV VE estimates, and MedImmune data on the new H1N1pdm09- like vaccine \nvirus that indicated a better immunogenicity and fitness of that new virus. \nUnfortunately, subsequently LAIV4 use within the CDC US VE networks has been low since the \n2018- 2019 season, which has precluded assessment of vaccine- specific VE in the US from \nthese networks. However, LAIV VE estimates have been published from non- US observational \nstudies.\n16 For comparison, an effort was made to pool from the same papers where available, \neither IIV inactivated vaccine quadrivalent VE estimates, or if such were not available, estimates \nfor all vaccines. These estimates are all for children for whom the age groups vary somewhat , \ngiven that they represent the age groups for whom vaccine was licensed. Starting with Finland \nfor 2018- 2019 , LAIV4 VE estimate for children 2─6 years of age was 36% and VE for IIV4 for \nchildren 6 months─6 years of age was 54%. For UK, 2018- 2019 VE for LAIV VE was 49% for \nchildren 2─17 years of age and 53% for all vaccines in this same age group. For 2019 -2020, \nestimated LAIV4 VE of 45% was reported in the UK for children 2─17 years of age. For 2021 -\n2022, estimated LAIV4 VE of 72% was reported in the UK fo r children 2─17 years of age. For \n2021- 2022 in Denmark, VE for all vaccines among non- hospitalized children 2─6 years of age \nwas 64% and was 63% for hospitalized children of the same age. This paper notes that these \nchildren were offered LAIV4, which 92% received. Others received inactivated vaccine, so these \nare predominantly LAIV4 estimates . \nACIP Discussion Points, Observations, Suggestions on Influenza Vaccine \nFollowing Dr. Grohskopf ’s First Presentation \n• Regarding questions about whether the pattern of the 111 pediatric death cases was \nsimilar to prior years with 50% having no co- morbidities, Dr. Grohskopf indicated this \nwas not yet known for this season. It takes a while for this information to come in, but the \n50% that was published in a 2018 paper from her group is fairly typical. \n• In terms of questions about why influenza began and peaked so early this season, Dr. Grohskopf noted that influenza seasons are unpredictable, and this is not the first time \nan early influenza season has occurred. She referred to a chart on the CDC webpage \nthat covers about 39 influenza seasons to date that shows a couple of seasons that peaked as early as October . \n• The hospitalization rate seems somewhat low despite the brisk influenza season, which raised questions about whether this was due to better diagnostics and therapeutics \nand/or better recognition of viral disease. Dr. Grohskopf indicated that this cannot be \ndiscerned form the type of data that come from that system, but it is certainly plausible to \n16 A) Stuurman et al Vaccine 2020;38:6455- 64632; B) Pebody, Vaccine 38 (2020) 489–4; C) Stuurman et al Vaccine 2021;39:3964-\n3973; D) https://webarchive.nationalarchives.gov.uk/ukgwa/20220401215804/https://www.gov.uk/government/statistics/annual -flu-\nreports ; E) https://www.gov.uk/government/statistics/annual -flu-reports/surveillance- of-influenza- and-other- seasonal -respiratory -\nviruses -in-winter- 2021- to-2022 ; and F) Emborg, Euro Surveill2022;27:pii=2200278 \n40 \n \n   \n    \n \n   \n \n    \n         \n \n          \n          \n   \n \n      \n       \n   \n    \n   \n     \n    \n     \n  \n       \n  \n   \n \n    \n \n  \n   \n  \n    \n   \n   \n \n \n      \n   \n     \n  \n \n \n   \n    \n   \n  \n  \n   \n  think that people have a lower index of wanting to get checked by a medical provider \ngiven all that everyone has been through over the last couple of years. Certainly, \ninfluenza seasons vary in severity. H3N2 seasons are generally more severe than \nH1N1, and there appears to be a reasonably good vaccine match. \nFollowing Presentations by Ms. Olson, Dr. Lewis, and Dr. Tenforde \n• Regarding an inquiry about what percentage of persons ≥65 years of age in the IVY and \nVISIONS studies received the preferentially recommend high- dose vaccine, Dr. \nTenforde indicated that most persons 18─64 years of age received standard- dose \ninactivated quadrivalent vaccines and the majority (90%) of individuals ≥65 years of age \nreceived either a high- dose vaccine or adjuvanted vaccine product. Dr. Lewis added that \nwhile they are awaiting more complete product data for IVY, the breakdown in the past has been similar with the majority of persons 18─64 years of age receiv ing standard-\ndose inactivated quadrivalent vaccines and the majority (90%) of individuals ≥65 years \nof age receiving some type of enhanced vaccine product. \n• With regard to an inquiry about how many children received LAIV, Ms. Olson indicated that LAIV uptake has been low within the NVSN Network facilities. \n• In terms of why SARS- CoV-2 was excluded from the analyses and if that changed the \ncomparisons to past years, Dr. Tenforde indicated that patients had to be negative for \ninfluenza and SARS- CoV-2 to be part of this analysis. Most patients who received \ninfluenza testing also received testing for SARS -CoV-2. The reason they were excluded \nas controls was because there is a potential for a confounding relationship where receipt \nof influenza vaccination is correlated with receipt of COVID -19 vaccination. Essentially , \ncontrols can be enriched with patients who had COVID -19 and potentially bias VE \nestimates. \n• It is important to highlight that among the pediatric deaths, only about 22% were fully vaccinated with 2 doses. \n• With respect to whether the WG is aware of any new influenza vaccines on the horizon with less disappointing efficacy, Dr. Talbot pointed out that everyone would like to find \nthe Holy Grail. A unique aspect of influenza infection in adults is that adults have been \nexposed to RSV and influenza many times in their lives. Yet, the vaccine is still being \nexpected to do something that the human immune system has not figured out. There are \nmultiple components to this , including the aging immune system , the changing virus, and \nthe vaccines primarily induce a B- cell response. There is some T- cell response, but \nthere is very little internal protein in current vaccines that would stimulate the T- cells. \nWhile many scientists including herself are looking for a universal influenza vaccine, they still have the vaccine that was developed originally for military recruits. It is somewhat \ncleaner and less reactogenic than it was when it was first discovered, and it still prevent s \na fair number of hospitalizations and deaths each year. Therefore, it will continue to be \nused until the Holy Grail appears. \nFollowing Dr. McClean’s Presentation \n• The prospective cohort study is intriguing. The incidence per 1,000 person -days of 0.82 \nfor the vaccinated and 1.79 for unvaccinated persons results in approximately 1 per \n1,000 person days. Based on a 3- month influenza season, the number needed to \nvaccinate (NNV) would be 10 people to prevent 1 illness. \n• Notably, the test -negative case- control study began in December and likely missed \nsome cases due to the early start of the influenza season. \n41 \n \n  \n    \n         \n    \n \n \n    \n    \n  \n    \n   \n \n  \n    \n      \n   \n   \n  \n   \n \n  \n \n \n \n \n          \n \n  \n    \n      \n    \n     \n   \n     \n   \n      \n   \n      \n       \n            \n  \n  \n \n    \n     \n     \n \n   \n        Following Dr. Grohskopf ’s Second Presentation \n• Notably, the measures , definitions , and criteria vary in the non-US studies. Dr. \nGrohskopf emphasized that some variations are expected because there are variations \nin matches from season- to-season and in methods, especially among observational \nstudies. \n• There appears to be a theme that this vaccine is unlike Coronavirus vaccine in that it \ndoes not seem to protect better against worse outcomes. It may be somewhat different \nfor ARI and hospitalization, but not as dramatically. It was not clear whether this was real or the way that people are being investigated. Dr. Grohskopf said that to be comple tely \nhonest, she was not sure. Much of the data she is familiar with on prevention of severe \noutcomes focuses more on influenza vaccines broadly, while she was less familiar with \nthe specifics on LAIV. She will look this up and provide a response at a later time. \n• One of the major challenges that will need to be addressed is that because people are able to test themselves at home, they may be less likely to go to their doctor. Those who \ndo present to medical settings are getting multiplex testing. As more point -of-care \ndiagnostics move into the home setting, consideration will have to be given to how \nmeaningful surveillance can continue to be conducted in that context. These data are \nneeded in order to continue to ensure the benefit -risk balance of prevention programs . \n• It would be beneficial to include LAIV information in any publications regarding VE, given \nthat many parents have questions and would like to see these data. \nPNEUMOCOCCAL VACCINES \nIntroduction \nKatherine A. Poehling, MD, MPH (ACIP WG Chair) reminded everyone that pneumococcal \nvaccines currently recommended for use in the US include PCV13 and PCV20 for adults . \nPCV13 and  PCV15 are recommended for children . PPSV3 has a risk -based recommendation \nfor children. PPSV3 is recommended for adults who previously received PCV13 or PCV15, but \nnot for those receiving PCV20 20. The goal is to move forward with fewer differences. As a \nreminder, all children under 2 years of age have the same pneumococcal vaccine \nrecommendation for 3 primary series and a booster, often known as the 3 + 1 schedule. The \nprimary series doses are administered at 2, 4, and 6 months and the booster is given at 12 to 15 \nmonths later. Currently, either PCV13 or PCV15 can be given to US children. Children with \ncertain underlying conditions are recommended to receive PPSV23 . Children with chronic \nmedical conditions (CMC), cerebrospinal fluid (CSF) leak, and cochlear implants are \nrecommended to receive PPSV23 ≥8 weeks after the conjugate vaccine. Children with \nimmunocompromising conditions are recommended to receive PPSV23 ≥8 weeks after the \nconjugate vaccine. Then ≥5 years later , a second dose of PPSV23 is recommended . Children \n6─8 years of age with CMC can receive PPSV23 if they did not receive pneumococcal \nconjugate vaccine. Of note, CMC includes chronic heart disease (CHD), chronic lung disease \n(CLD),and diabetes mellitus (DM) . \nApproval of PVC20 use among children is anticipated later this year. It is anticipated that later in \nQuarter 2 of 2023 , pediatric PCV20 will be approved. Pediatric PCV15 use was approved in \nJune 2022. With that in mind, the WG is considering the following policy questions: \nShould PCV20 be recommended as an option for pneumococcal conjugate vaccination \naccording to currently recommended dosing and schedules for US children aged <2 years ? \n42 \n \n    \n   \n   \n \n \n   \n \n      \n \n \n \n     \n   \n    \n   \n    \n     \n     \n    \n    \n    \n \n \n   \n  \n \n   \n     \n   \n \n \n       \n \n  \n \n  \n \n \n Should PCV20 without PPSV23 be recommended as an option for pneumococc al\nv\naccination for US children aged 2 ─18 years of age with underlying medical conditions tha t\ni\nncrease the risk of pneumoc occal diseas e?\nP\nresentations during this session focused on the epidemiology of pneumococcal disease \namong US children, pediatric outpatient ARI visits and antibiotic use attributable to serotypes in \nhigher valency pneumococcal conjugate vaccines, PCV20 P hase 2/ 3 study results among \nchildren, preliminary E tR for PCV20 use in children, and WG considerations and next steps. \nEpidemiology of Pneumococcal Disease among US Children \nRyan Gierke, MPH (CDC/NCIRD) presented an update on the current epidemiology of pediatric \npneumococcal disease in the US , beginning with a background on the spectrum of \npneumococcal disease. Pneumococcus is transmitted through airborne droplets from person -to-\nperson. It can colonize i n the nas opharynx and can be spread locally to the ears to cause otitis \nmedia. It also can be aspirated and cause pneumonia. Pneumococcus also can infect the blood \nand cause septicemia. These different infections can be characterized as either noninvasive \ndisease or invasive disease. Invasive pneumococcal disease (IPD) is a less frequent but severe \nform of the illness. Noninvasive disease is more frequent . In children, otitis media is one of the \nmost common forms of pneumococcal disease. Note that pneumococ cal pneumonia can be \neither invasive or noninvasive, depending on whether a sterile body site like blood becomes \ninfected in addition to the lungs. This presentation focused on: 1) IPD data in terms of the impact of pneumococcal conjugate \nvaccines (PCVs ) and IPD incidence and serotype distribution; IPD incidence caused by \nserotypes covered in the new conjugate vaccines, PCV15 and PCV20; and changes in IPD \nincidence and serotype distribution resulting from the COVID -19 pandemic ; 2) the impact of \nPCV13 on acute otitis media (AOM) and incidence estimates; and 3) the impact of PCV13 on \nall-cause and pneumococcal pneumonia in children and recent estimates of pneumonia \nincidence. \nIn terms of the impact of pneumococcal conjugate vaccines on pediatric IPD incidence and \nserotype distribution among children in the US, data on IPD are obtained from the Active \nBacterial Core (ABCs) s urveillance system, which provides population- based surveillance at 10 \nsites across the US. Those are defined as pneumococcus -isolated from a normally sterile site in \nresidents of the 10 surveillance areas shown in the map below: \n43 \n \n   \n  \n   \n   \n  \n   \n      \n    \n  \n \n    \n     \n \n \n \n \n    \n    \n   \n     \n     \n   \n   \n   \n     \n   \n \n \n    \n     \n   \n  \n  \n \n \n \n \n  \n   \n  \n  \n \n \n Isolates are serotyped at reference laboratories using whole- genome sequencing (WGS) , \nQuellung, or PCR at reference laboratories . For analysis purposes, serotypes are grouped by \nvaccine types. US Census Bureau estimates were used as denominators to calculate incidence \nrates for overall and serotype- specific IPD and are presented as cases per 100,000 persons. \nFrom 1998─2019, b efore introduction of conjugate vaccines in the US, incidence rates of IPD \namong children <5 years of age were approximately cases per 100,000 persons. PCV13 -type \nIPD caused the majority of disease. Note that 6C included with the PCV13 serotypes due to \ncross- protection provided from the 6A antigen included in the vaccine. After the introduction of \nPCV7 in 2000, rates of IPD declined significantly. There were additional declines in disease following PCV13 introduction in 2010. Around 2013, declines in PCV13-type IPD rates \nplateaued at <2 cases per 100,000. This trend continued onward through 2019. Rates of overall \nIPD are now <10 cases per 100,000 persons, with much of the remaining disease caused by \nnon-PCV13 serotypes. \nFocusing on more recent years from 2007─ 2021 , the COVID -19 pandemic resulted in a 50% \nreduction in rates of overall IPD in 2020 compared with 2018─2019. However, rates began to \nrebound in 2021 with a 30% increase compared to 2020 rates. Data for 2022 are not yet \nfinalized, but looking at 2021 data by month, the monthly rates of IPD were back to the pre -\npandemic levels after around August 2021. IPD rates were examined for individual serotypes in \nPCV13 among children <5 years of age from 2011 ─2021. After PCV13 introduction in children, \nrates of IPD declined for many PCV13 serotypes. However, reductions were not seen in \nserotype s 3 or 19F. Together, these serotypes accounted for almost 80% of remaining PCV13-\ntype disease in 2018 and 2019. The impact of the COVID -19 pandemic led to a change in the \nserotype distribution of PCV13- type disease . In 2020 and 2021, serotype 19F rebounded \nquickly and now accounts for the majority of remaining disease, while the proportion caused by \nserotype 3 has declined. This will continue to be monitored to determine whether these changes \ncontinue. \nNow to review the current pediatric IPD burden among PCV15 and PCV20 serotypes , this table \nshows the serotypes contained in the 3 conjugate vaccines and PPSV23. Serotypes covered by \nPCV13 are shown in yellow ; additional serotypes covered by the new conjugate vaccines, \nPCV15 and PCV20, are shown in green; and PCV15 contains the 13 serotypes included in \nPCV13 plus serotypes 22F and 33F : \nFor analysis purposes: PCV13+6C: includes serotype 6C with PCV13 types due to cross protection from 6A antigen\nPCV15 non- PCV13: includes serotypes 22F and 33F\nPCV20 non- PCV15 : includes serotypes 8, 10A, 11A, 12F, and 15B\nPPSV23 non -PCV20: includes serotypes 2, 9N, 17F, and 20\n44 \n \n     \n   \n  \n    \n         \n      \n     \n   \n \n    \n    \n  \n  \n  \n  \n \n       \n  \n \n    \n     \n    \n \n  \n  \n  \n   \n    \n     \n \n   \n     \n \n     \n     \n     \n       \n   \n  \n \n       Rates of IPD incidence among children <5 grouped by vaccine type from 2011─ 2021 remained \nrelatively stable for PCV15 /non-PCV13 and PCV20/ non-PCV15 serotypes in recent years \nbefore the COVID -19 pandemic. Although rates of IPD were lower in 2020 and 2021, PCV15 / \nnon-PCV13 and PCV20/ non-PCV15 serotypes still account for a similar proportion of IPD at \naround 15% each. There has been great variability over the years among children 5─18 years \nof age, which is likely due to having much fewer number of cases. Unlike what was observed for \nyounger children, IPD did not start to rebound in 2021 among children 5─18 years of age. \nChildren with immunocompromising conditions are at increased risk of IPD. In terms of IPD \namong children with select immunocompromising conditions, children <5 years of age with a \nhematologic malignancy had rates of IPD around 230 times higher than children without a \nhematologic malignancy. African -American children with sickle cell disease had rates of IPD at \naround 30 to 70 times higher than African- American children without sickle cell disease, \ndepending upon their age. Among children with immunocompromising conditions, a higher \nproportion of IPD is caused by non -vaccine serotypes compared to children without \nimmunocompromising conditions. \nTo review the impact of PCV13 on AOM and available data on incidence estimates for AOM,17 \nAOM is a major cause of childhood morbidity and pneumococcus is a common cause of AOM, \naccounting for around a quarter of bacterial AOM. Studies have shown that AOM incidence has \ndecreased after PCV13 introduction, with declines ranging from 11% to 14% depending on the \nage groups and years examined. AOM estimates vary among studies, but incidence is \nconsistently highest among children <5 years of age. \nRegarding the data on the impact of PCV13 on all -cause and pneumococcal pneumonia and \nestimated incidence of pneumonia in children , multiple studies have shown reductions in all -\ncause and pneumococcal pneumonia among children following introduction of PCV13. Reductions in all -cause pneumonia range from 17% to 35% among children, depending on the \nage group, with reductions largest among children <2 years of age . There was an estimated \n40% reduction in pneumococcal pneumonia among children <1 year of age and a 51% \nreduction in pneumonia among children 5─17 years of age . To summarize all -cause pneumonia \nand all -cause inpatient pneumonia incidence estimates in cases per 100,000 person years \namong children , pneumonia incidence is lower than AOM incidence but higher than IPD \nincidence. Again, the highest incidence is observed among children <5 years of age. \nIn conclusion, the use of PCVs has significantly decreased the incidence of pneumococcal \ndisease in US children. However, risk of disease remains higher among children with \nimmunocompromising conditions compared to those without. In 2018 and 2019, the proportion \nof IPD caused by vaccine serotypes was about 15% of IPD for PCV15 /non-PCV13 serotypes \nand about 30% of IPD for PCV20 /non-PCV13 serotypes. \n17 Tong et al. BMC 2018; King et al. ASHE 2021; Casey et al Clin Pediatr 2014; Kaur et al. EJCMID 2022 \n45 \n \n  \n     \n \n \n      \n  \n   \n  \n   \n    \n    \n      \n   \n     \n   \n   \n  \n \n  \n      \n    \n   \n   \n  \n   \n       \n      \n   \n     \n  \n \n \n  \n    \n  \n  \n     \n     \n \n \n    \n     \n    \n    \n     \n   \n    \n   \n \n  \n  \n     Estimating the Impact of Higher -Valency PCVs on Pediatric Outpatient ARI Visits and \nAntibiotic Use \nLaura King, MPH (UC Berkeley) presented results from a University of California Berkeley \nstudy estimating p ediatric outpatient ARI visits and antibiotic use attributable to serotypes in \nhigher valency PCVs. This presentation focused on pediatric outpatient visit and anti biotic \nprescription incidence, AOM vaccine serotype attributable proportion and incidence, and \nsinusitis and pneumonia vaccine serotype attributable proportion and incidence. In terms of \nbackground, ARIs account for a large proportion of all outpatient visits and antibiotic \nprescriptions among children. Previous work looking at a commercially -insured population \nestablished that there were over 1,200 ARI visits per 1,000 children in 2018.18 A separate study \nestablished that there were about 250 ARI -associated antibiotic prescriptions per 1,000 children \nissued from US doctors ’ offices and EDs per year in 2014 and 2015.19 Streptococcus \npneumoniae (S. pneumoniae) is a known etiology of several ARIs, including AOM , sinusitis, and \npneumonia. However, the contribution of pneumococcus to the total burden of these conditions \nand the visits and antibiotic prescriptions associated with them is still unknown. \nTime series data demonstrate decreases in outpatient visits and antibiotic use associated with \nPCVs. A previously published study examining the number of all antibiotic prescriptions per \n1,000 persons stratified by age group20 showed that the rate of antibiotic prescriptions \ndecreased from 2011 to 2014, coinciding with uptake of PCV13 after its introduction in 2010. \nThis decrease was especially pronounced in children <2 years of age, the age group eligible for \nvaccination. In considering PCV20 and PCV15 for pediatric use, it is important to better \nunderstand the potential impacts of these higher valency vaccines on outpatient visits and \nantibiotic use. This was the impetus for the current study with an overall objective to estimate \nthe incidence of pediatric outpatient visits and antibiotic prescriptions for AOM , sinusitis, and \npneumonia caused by S. pneumoniae serotypes found in the new higher valency PCVs, PCV15 \nand PCV20. This study focuses on the additional serotypes in PCV15 and PCV20 that are not in \nPCV13 to quantify the additive potential of these vaccines. These are referred to as PCV20 -13 \nand PCV15- 13 serotypes. \nThe study focuses specifically on AOM , abbreviated AOM, sinusitis, and pneumonia as these \nare ARIs with established pneumococcal involvement. The overall study objective is composed \nof two parts , which are to: 1) estimate the incidence of all- cause visits and antibiotic \nprescriptions for these conditions; and 2) estimate the proportion of outpatient disease caused \nby PCV15 -13 and PCV20- 13 serotypes. Multiplying the results from these 2 components will \nprovide the incidence of visits and antibiotic prescriptions for these conditions attributable to \nPCV15 -13 and PCV20- 13 serotypes. \nBeginning with the first project component to estimate all-cause vi sit and antibiotic prescription \nincidence for AOM, pneumonia, and sinusitis , 2 data sources were used to capture visits and \nantibiotic prescriptions across all outpatient settings in the US. Visits to and antibiotic \nprescriptions from physician offices and EDs were estimated using the National Ambulatory \nMedical Care Survey (NAMCS ) and the National Hospital Ambulatory Medical Care Survey \n(NHAMCS ). These are nationally representative surveys administered by CDC ’s National \nCenter for Healthcare Statistics (NCHS) . Data were used from 2016 and 2018, as later years \nand in 2017 were not available in NAMCS at the time of the analysis. Because NAMCS and \n18 King LM, et al. Antimicrob Steward Healthc Epidemiol. 2021;1(1):1- 8. doi: 10.1017/ash.2021.230 \n19 Hersh AL, et al. Clin Infect Dis. 2021;72(1):133- 137. doi: 10.1093/cid/ciaa667 \n20 King et al., Clin Infect Dis. 2020; 70(3):370- 377). doi: 10.1093/cid/ciz225 \n46 \n \n   \n   \n  \n      \n     \n    \n     \n    \n    \n  \n \n       \n    \n   \n  \n    \n   \n   \n    \n  \n \n     \n  \n    \n    \n     \n   \n  \n    \n   \n     \n    \n \n \n \n     \n     \n    \n  \n   \n   \n   \n   \n     \n      \n   \n  \n  \n     \n  NHAMCS only cover physician offices and EDs, the MarketScan Commercial and Medicaid \nDatabases were used to estimate visits and prescribing in alternative outpatient settings such as \nurgent care and retail health clinics. In both datasets, a single diagnosis was assigned to each \nvisit using an established tiered methodology that prioritizes diagnoses most likely to result in an \nantibiotic prescription. All incidence estimates were standardized per 1,000 person -years at risk \nand total incidence was estimated by combining the sum of the estimates from NA MCS , \nNHAMCS , and Market Scan. Using those methods, total incidence of outpatient visits for all 3 \nconditions was estimated to be 208 visits per 1,000 person -years . Total incidence of outpatient \nantibiotic prescriptions was estimated to be 181 prescriptions per 1,000 person- years . Notably , \noverall incidence was driven primarily by AOM . \nIn terms of the second project component and estimating vaccine serotype attributable \nproportions and incidence, it is important to note that there are several major challenges in \nevaluating pneumococcal and serotype -specific contributions to outpatient disease. First, \nchildren are frequently colonized with pneumococcus . Published estimates of nasopharyngeal \npneumococcal carriage range from 11% to 60% in healthy children from h igh-income countries. \nSecond, samples from infection sites are not regularly obtained for outpatient pneumococcal disease. There are some studies using samples of middle ear fluid in children with AOM. \nHowever, the children sampled in these studies often have severe or recurrent disease. Third, \nfew studies have been conducted for non- AOM ARIs in pediatric outpatients. \nGiven these challenges, 3 methods were used to estimate the proportion of outpatient AOM \nattributable to PCV15- 13 and PCV20- 13 seroty pes. All of these methods have their own \nlimitations, and no one method is likely definitive. However, using multiple methods allowed for \nestimation of ranges of likely values, taking into account the uncertainties inherent in estimating \netiology in outpatient disease. For all methods, previously published data were used to generate \nestimates. The first method used was a vaccine probe approach. In vaccine probe studies, VE \nagainst vaccine type in all -cause disease is used to estimate the proportion of disease \nattributable to a specific pathogen, in this case, the vaccine serotypes. The second approach \nused considered pneumococcal prevalence and serotype distribution for middle ear fluid \nsampled from children with AOM to estimate attributable proportions. The third approach used \ndifferen tial nasopharyngeal carriage prevalence in children with AOM and healthy children to \nestimate the pneumococcal attributable proportion and combined this with the distribution of \nserotypes and carriage in children with AOM. \nUsing these 3 methods, pneumococcus was estimated to account for 14 % to 22% of outpatient \nAOM cases , PCV15 -13 serotypes account ed for 0.7 % to 1% of outpatient AOM, and PCV20- 13 \nserotypes account ed for 3.7 % to 5.1% of outpatient AOM. The highest attributable percents \nwere observed from the approach using pneumococcal prevalence and serotype distribution in \nmiddle ear fluid. Regardless of method, the distribution of vaccine serotype groups remained \nfairly constant, with PCV20- 13 serotypes accounting for about 5 times the proportion of \noutpatient disease covered by PCV15- 13 serotypes. Using these attributable percents and the \nall-cause AOM visit and prescription incidence data presented earlier, incidence was estimated \nfor outpatient visits per 1,000 person- years and the annual number of outpatient AOM visits in \nchildren. It was estimated that 76 ,000 to 109,000 visits per year were attributable to PCV15- 13 \nserotypes and 397,000 to 543,000 visits were attributable to PCV20- 13 serotypes. Looking at \nthe same data for AOM -associated antibiotic prescriptions , PCV15 -13 serotypes were \nassociated with 65,000 to 93,000 outpatient antibiotic prescriptions annually and PCV20- 13 \nserotypes were associated with 340 ,000 to 464,000 outpatient antibiotic prescriptions annually. \n47 \n \n   \n     \n    \n   \n   \n     \n     \n   \n     \n   \n   \n         \n   \n   \n    \n     \n    \n  \n  \n \n    \n    \n  \n   \n  \n   \n \n \n    \n    \n  \n   \n       \n       \n \n \n   \n   \n   \n   \n    \n  \n \n    \n   \n  Regarding the attributable proportion and incidence estimates for pneumonia and sinusitis , less \ndata were available for these conditions. The ability to estimat e attributable proportions in \npneumonia and sinusitis was limited to the vaccine probe and differential carriage approaches. \nUsing these methods, 12 % to 18% of pediatric outpatient pneumonia were estimated to be \nattributable to pneumococcus . PCV15 -13 serotypes account ed for less than 1% of outpatient \npediatric pneumonia cases and PCV20- 13 serotypes accounted for 2.8 % to 4.4% of outpatient \npediatric pneumonia cases. The attributable proportions were multiplied by the all -cause visit \nand antibiotic prescription estimates presented earlier , which estimate d that PCV15 -13 \nserotypes account ed for 9,000 to 14,000 visits and 7,000 to 11,000 antibiotic prescriptions for \noutpatient pediatric pneumonia per year . PCV20 -13 serotypes account for 43,000 to 68,000 \nvisits and 34 ,000 to 53,000 antibiotic prescriptions for outpatient pediatric pneumonia per year. \nFor sinusitis, it was estimated that 12% to 30% of all outpatient pediatric cases were attributable \nto pneumococcus . PCV15 -13 serotypes account ed for 0.6 % to 1.5% of sinusitis cases and \nPCV20 -13 serotypes account ed for 2.8 % to 7.3% of sinusitis cases. The differential carriage \nestimates were the same for pneumonia and sinusitis because the same estimates were used \nfor all non- AOM ARIs in that approach given the scarcity of data. For sinusitis, it was estimated \nthat PCV15- 13 serotypes account ed for 17,000 to 44,000 visits and 16 ,000 to 43,000 antibiotic \nprescriptions per year . PCV20 -13 serotypes account ed for 82,000 to 216,000 visits and 79 ,000 \nto 209,000 antibiotic prescriptions per year. \nTo summarize the ranges of point estimates for each condition by vaccine serotype group \nestimated using the multiple methods described earlier, for all 3 conditions, PCV15- 13 \nserotypes account ed for 1.9 % to 3.4% of outpatient disease in children, translating to 103,000 to \n168,000 pediatric outpatient visits and 90,000 to 148,000 outpatient antibiotic prescriptions \nannually in the US. PCV20- 13 serotypes account for 9.4% to 16.8% of outpatient AOM, \npneumonia, and sinusitis, translating to 527,000 to 831,000 pediatric outpatient visits and \n458,000 to 731,000 outpatient antibiotic prescriptions annually in the US. \nThis study had several limitations. First, it relied upon previously published data to estimate \nattributable proportions. Consequently, although data on pneumococcus in all outpatient \nconditions was limited, this was especially true for sinusitis and pneumonia. Therefore, it was \nnecessary to rely on AOM as a proxy for these conditions in some cases. Additionally, due to \ndata limitations at the time of the analysis, the incidence estimates were based on all- cause \nincidence data from 2016─ 2018. Finally, it was assumed that healthcare utilization was constant \nacross serotypes for outpatient disease. \nIn conclusion, this study estimated that the additional serotypes included in PCV15 and PCV20 \naccounted for approximately 100,000 to 830,000 outpatient visits and 90,000 to 730,000 \noutpatient antibiotic prescriptions for AOM, pneumonia, and sinusitis in US children annually. \nSpecifically, PCV15 -13 serotypes account ed for 103,000 to 168,000 visits and 90,000 to \n148,000 antibiotic prescriptions . PCV20 -13 serotypes account for 527,000 to 831,000 visits and \n458,000 to 731,000 antibiotic prescriptions. The percent of outpatient disease attributable to \nPCV2 0-13 serotypes was greater than the percent attributable to PCV15- 13 serotypes. As a \nresult, the estimated incidence of outpatient pediatric visits and antibiotic prescriptions \nattributable to PCV20- 13 serotypes was 4 to 5 times that attributable to PCV15 -13 serotypes. \n48 \n \n  \n \n \n   \n   \n    \n \n    \n   \n     \n      \n   \n  \n  \n   \n   \n  \n \n  \n \n \n \n \n  \n       \n    \n    \n   \n \n \n      \n   \n     \n  \n    \n     \n    \n   \n      PCV20 Phase 2/3 Study Results among Children \nWendy Watson, MD (Pfizer) presented key results from Pfizer’s PCV20 Pediatric Clinical \nDevelopment Program from the Phase 2/3 trial. PCV20 is built on the 20- plus year legacy of \nPCV7 and PCV13 . PCV20 contains all of the components of PCV13, with 7 additional \nconjugates. Pfizer is seeking to expand PCV20 currently licensed in adults to include the same \npediatric indications as PCV13. PCV20 builds upon the clinical experience of previous \ngenerations of PCV7 and PCV13 . PCV7 was licensed based on a randomized controlled clinical \n(RCT) efficacy trial of IPD in California. In this study of 38,000 infants, high efficacy was \ndemonstrated. Subsequently, high VE was shown following PCV7 introducti on. When PCV13 \nwas developed to expand protection against 6 additional serotypes, it was not considered \nfeasible to perform an efficacy trial. Therefore, a licensing pathway similar to other vaccines, like \na conjugate vaccine, was pursued. Immunogenicity bridging comparing PCV13 to PCV7 was \nused to support licensure globally. Similarly, PCV20 licensure for pediatrics will be based on \nimmunogenicity bridging with non- inferiority comparisons to PCV13—a vaccine that now has \nmore than 10 years of demonstrated effectiveness against disease due to vaccine serotypes. \nThis table shows the studies Pfizer submitted to the FDA to support the PCV20 pediatric \nindication: \nThese pediatric studies were generally modeled on the PCV13 pediatric studies and consist ing \nof Phase 2 and Phase 3 studies. The studies listed in the table were conducted in children in the \nUS, including Puerto Rico, except for the safety study on the bottom row that also included \ninfants from other countries. For this presentation, Dr. Watson focus ed on the pivotal \nimmunogenicity study in infants in the second row and the single dose study in children in the \nthird row. \nThe Phase 3 pivotal infant trial was a multi- center , randomized , double- blind study enrolling \ninfants in the US, including Puerto Rico. The study enrolled approximately 2,000 participants \nwho were randomized equally to receive 4 doses of PCV20 or PCV13. PEDIARIX and HIBERIX \nwere given concomitantly with the first 3 doses and MMR and varicella vaccines were given with \nthe fourt h dose. Influenza and rotavirus vaccines were permitted to be given with study vaccine \nin age-eligible participants. Blood was collected for immunogenicity assessments 1 month after \nthe third dose, before the fourth dose, and 1 month after the fourth dose. The primary study \nobjectives were to : 1) describe safety ; 2) evaluate the immunogenicity of PCV20, including non-\ninferiority comparisons of PCV20 to PCV13; and 3) assess responses of specific concomitantly \n49 \n \n  \n   \n \n  \n   \n   \n      \n    \n   \n    \n    \n    \n     \n     \n  \n  \n  \n   \n \n   \n    \n    \n      \n     \n      \n      \n   \n     \n \n \n      \n   \n    \n       \n    \n      \n      \n  \n      \n       \n      \n     \n \n \n   \n       \n       \n     \n      \n   \n         administered vaccines. In terms of the dispositio n and demographics of the study population, \nthe groups were well -balanced with respect to sex, race, and ethnicity. \nPCV generate complex and diverse cellular and humoral immune responses that play a role in \nimparting protection. The primary and key secondary objectives that were agreed to \nprospectively with the FDA include 2 co- primary objectives to assess noninferiority of \nimmunoglobulin G (IgG) geometric mean concentrations ( GMCs ) after the toddler dose and \nassess n oninferiority of the percentage of participants with IgG above predefined levels after the \ninfant series. The key secondary objective was to assess noninferiority of IgG GMC after the \ninfant series . Other aspects of the responses also were assessed, including other IgG \nrespons es, functional antibodies measured as opsonophagocytic activity (OPA) titers, and \nboosting of IgG and OPA antibody levels that are indicative of immune memory. The \nassessment of the totality of data for serotypes that missed non -inferiority was agreed to \nprospectively by the FDA. An example of how important this assessment is comes from the \nprevious experience with PCV13 and serotypes 6b and 9b. These 2 serotypes missed a co-\nprimary objective for non -inferiority compared to PCV7, but the totality of immunogenicity data \nsupported licensure and subsequent real -world effectiveness has shown that PCV13 protects \nagainst IPD caused by these two serotypes. \nFor the co -primary objective percentage of participants with the predefined IgG concentration \nafter dose 3, non-inferiority was declared if the 95% confidence interval of the difference was \ngreater than - 10%. The additional 7 serotypes were compared to the lowest result in the PCV13 \ngroup, excluding serotype 3. In this case, the comparison was to serotype 23F result in the \nPCV13 group. For this objective, non -inferiority was met for 14 serotypes and 6 serotypes \nmissed non-inferiority, although serotypes 1, 4, 9V, and 23F missed statistical non- inferiority by \nonly a small margin. Serotypes 3 and 12F missed by a gr eater margin, but the totality of data \nwas supportive. Additionally, public reference standard that was used to calculate 12F IgG \nconcentrations may be underestimating 12f IgG results . Pfizer has shared these findings with \nthe FDA. \nContinuing to look at t he response after Dose 3, the IgG GMC ratios in the PCV20 group \ncompared to the PCV13 group for each vaccine serotype was the key secondary objective in \nthe study. Non-inferiority was to be declared for this objective if the lower bound of the 95% \nconfidence interval of the ratio was greater than 0.5. All 20 serotypes met non- inferiority for this \ncomparison, including serotypes 3 and 12F. There also was comparison of the 7 additional \nserotypes to the result of a vaccine serotype in the PCV13 group. The IgG GMCs to those 7 \nadditional serotypes in the PCV13 group after Dose 3 were low. The IgG GMC s for the 7 \nadditional serotypes were substantially higher in the PCV20 group compared to the PCV13 \ncontrol group. This was also the case after Dose 4. Functional antibodies elicited by the vaccine \nafter Dose 3 also were assessed. The OPA GMC responses for the 13 matched serotypes were \nsimilar between groups, even for serotypes that missed the co -primary IgG objective for this \ndose. PCV20 also elicited very robust functional activity to the 7 additional serotypes, including \n12F. \nMoving on to the response after the toddler dose, Dose 4 in the study , non-inferiority was \ndeclared if the lower confidence interval was above 0.5. Similar to the result for the IgG GMC \nratios after Dose 3, all 20 vaccine serotypes met non- inferiority after Dose 4. An important \nproperty of conjugate vaccines is their ability to elicit memory responses. Looking at the \nantibody levels in the PCV20 group after Dose 3 and after Dose 4 , it is clear that there were \nnumerically higher antibody levels after the toddler dose than after the infant series. This was \nobserved for both IgG GMCs and OPA GMTs for the vaccine serotypes. This indicates that \n50 \n \n     \n  \n \n    \n   \n     \n      \n    \n \n \n    \n     \n \n    \n    \n     \n    \n      \n         \n      \n  \n   \n    \n     \n  \n    \n  \n \n \n  \n   \n     \n   \n    \n  \n      \n  \n \n \n   \n \n    \n   \n        \n     \n   \n      \n  \n \n  immune response after the toddler dose is a significant marker indicating that a memory \nresponse has been induced after the infant series by PCV20. \nIn addition to evaluating the pneumococcal responses, Pfizer evaluated responses to \nconcomitant vaccines. Regarding the difference in percent of part icipants with pre- specified \nantibody levels to the different antigens in PEDIARIX and HIBERIX given with the 3 infant doses \nof PCV20 or PCV13 , all met the non- inferiority criteria. In terms of the responses to MMR and \nvaricella vaccines given with D ose 4 of PCV20 or PCV13 , all met the non- inferiority criteria. \nThese data support PCV20 use in routine pediatric schedules. \nRegarding safety , injection site pain, drowsiness, and irritability were the most common events. \nMost reactions were mild or moderate , rates were similar across both groups , and were \nconsistent with the historical experience with PCV13. As mentioned previously, another \nimportant Phase 3 study assessed the safety and immunogenicity of a single dose of PCV20 in \nchildren 15 months to less than 18 years of age. This study was conducted in the US to support \nthe use of PCV20 in children through 17 years of age. This multi- center,  single arm trial enrolled \napproximately 800 healthy participants of approximately 200 per age group. Partic ipants 15 \nmonths ─5 years of age were required to have documentation of at least 3 doses of PCV13 prior \nto enrollment. In terms of IgG GMCs for the 2 age groups less than 5 years of age, 1 dose of \nPCV20 elicited a robust IgG response to all 20 serotypes in children 15 to <24 m onths and 2 to \n<5 Years previously vaccinated with PCV13. Data from the youngest group also supports the \npotential for replacement of PCV13 with PCV20 in the schedule. There was a similar pattern in \nthe functional antibody responses in these age groups , as well as IgG and OPA responses in \nolder children. The safety data were consistent with historical experience with PCV13. There \nwere no clinically significant differences in the AEs in the PCV20 and PCV13 control group. \nSAEs were reported in 4.5% of PCV20 recipients and 3.7% of PCV13 recipients in the infant \nstudies supporting US licensure. No SAEs in this dataset were considered to be related to \nvaccine and no deaths were reported. \nIn summary, PCV20 is well- tolerated when administered as a 4-dose series to infants and as a \nsingle dose to toddlers through older children, with a safety profile similar to PCV13. The totality \nof data shows that PCV20 elicits IgA, IgG, and OPA responses in infants for all vaccine \nserotypes consistent with PCV13. A single dose of PCV20 elicited IgG and functional immune \nresponses to all 20 serotypes in children 15 months to less than 18 years of age, including \nthose with prior PCV13. PCV20 is compatible with routine pediatric vaccines. PCV20 is currently \nunder review by the FDA for use in pediatric populations 6 weeks to less than 18 years of age, \nwith a target action date in April 2023. PCV20 has the potential to address the substantial \nburden of pneumococcal disease in children. \nPreliminary EtR /GRADE for PCV20 use in US Children \nMiwako Kobayashi, MD, MPH (CDC/NCIRD) provided the EtR Framework for PCV20 use in \nUS children, pointing out that while the EtR includes 7 domains, the focus of this session would cover 3 of the domains: P ublic Health Problem, Benefits and Harms, and Equity. Currently , all \nchildren under 2 years of age have the same pneumococcal vaccine recommendations to \nreceive either PCV13 and PCV15 using a 3- dose series at 2, 4, and 6 months of age and a \nbooster dose at 12 to 15 months of age. Children ≥2 years of age with certain underlying \nconditions are recommended to receive PPSV23 in addition. \n51 \n \n  \n   \n \n   \n    \n \n  \n \n \n \n   \n   \n   \n  \n    \n \n \n   \n   \n   \n   \n   \n  \n  \n     \n   \n   \n     \n \n \n     \n    \n       \n \n    \n   \n \n \n     \n      \n    \n      \n  \n   \n  \n   \n  \n  \n  \n \n       For this EtR analysis, there were 2 policy questions: \nShould PCV20 be recommended as an option for pneumococcal conjugate vaccination \naccording to currently recommended dosing and schedules for US children aged <2 years? \nShould PCV20 without PPSV23 be recommended as an option for pneumococcal vaccination for US children aged 2– 18 years with underlying medical conditions that \nincrease the risk of pneumococcal disease? \nCombined into the PICO question regarding whether PCV20 should be recommended as an \noption for pneumococcal vaccination for US children, the population is all US children aged <2 \nyears and US children aged 2–18 years with underlying medical conditions. The comparison is \nthe current recommendations for the respective groups. The critical outcomes include: Vaccine-Type IPD ( VT-IPD), VT-Pneumonia, VT -AOM, VT -Pneumococcal Deaths, and SAEs F ollowing \nVaccination. \nBeginning with the Public Health domain, use of pneumococcal conjugate vaccines significantly \ndecreased the incidence of pneumococcal disease in US children. Outpatient acute respiratory \nillness caused by pneumococcus such as AOM , sinusitis, and pneumonia are common causes \nof outpatient visits and antibiotic prescribing. The risk of disease remains high in children with \nunderlying conditions that increase the risk of pneumococcal disease. In 2018─2019, the \nproportion of IPD caused by vaccine serotypes was approximately 30% for additional serotypes \ncontained in PCV20 but not in PCV13 and 15% for additional serotypes contained in PCV15 \nand not in PCV13.\n21 The WG determined that pneumococcal disease is of public health \nimportance for both groups of children. There was variability in the WG’s interpretation for \nchildren <2 years of age due to the significant reductions in pneumococcal disease among \nthese children. However, most WG members agreed that pneumococcal disease continues to \nbe of public health importance due to the remaining disease burden. \nFor the B enefits and Harms domain, the WG interpretation of this domain was informed \nprimarily by the great evidence profile for the PICO question. The outcomes deemed critical \nwere VT-IPD, VT-pneumonia, VT-AOM, and VT-pneumococcal deaths. Given that there are \ncurrently no studies assessing PCV20 effectiveness against these clinical outcomes , PCV20 \nimmunogenicity studies were used as evidence for these outcomes. To supplement this, the \nWG also reviewed post -licensure PCV13 and PPSV23 effectiveness data against these \noutcomes as a background. \nRegarding outcomes related to harms, WG members deemed SAEs as being of critical \nimportance. Evidence of SAEs was available and reviewed for PCV20. First, a summary of the \npost-licensure PCV13 VE data. Several post -licensure studies assessed PCV13 effectiveness \nagainst IPD. In general, these studies showed that PCV13 is highly effective against VT-IPD. \nData on PCV13 effectiveness against VT-pneumonia in children are limited. Based on the 2 \nstudies done in China and Israel, PCV13 is likely to be protective against VT-pneumococcal \npneumonia, but with a wide confidence interval. Data on PCV13 effectiveness against VT-\npneumococcal AOA also are limited. Estimates from these studies also tend to have wide \nconfidence intervals, though the data suggest that PCV13 is likely protective against VE-\npneumococcal AOM . \n21 Gierke. February 2023 ACIP meeting presentation; King. February 2023 ACIP meeting presentation \n52 \n \n  \n     \n    \n \n  \n      \n    \n \n   \n      \n  \n   \n    \n       \n   \n   \n   \n      \n  \n      \n      \n  \n \n \n    \n  \n   \n     \n   \n   \n \n    \n  \n    \n   \n     \n \n  \n  \n \n  \n   \n    \n   \n   \n     \n Data on PPSV23 effectiveness against pneumococcal disease in children with underlying \nconditions are limited.22 A study conducted before the introduction of PCV in the US showed \nthat PPSV23 is protective against VT-IPD among children with underlying medical conditions.23 \nData on PPSV23 effectiveness against non- invasive pneumococcal disease in children are even \nmore limited. In a recent systematic review, no studies were identified that assessed PPSV23 \nVE against AOM . Two RCTs that evaluated the efficacy of administrating both PCV7 and \nPPSV23 against AOM did not show any efficacy in the intervention groups.24 \nTo summarize the data on PCV20 use in children, the WG conducted a systematic review of \nliterature on PCV20 use among children.25 Overall, 4 studies were included for GRADE \n(Grading of Recommendation Assessment, Development and Evaluation) . Of these, 3 were \nconsidered for evidence of routine PCV20 use and 1 was considered for evidence of PCV20 \nuse in children with underlying medical conditions. Evidence of benefits of PCV20 use among \nchildren <2 years of age was informed by 2 RCTs (Phase II and III) that randomized healthy \nchildren to receive either PCV13 or PCV20.26 In the pivotal trial , PCVs were given using the 3-\ndose primary series followed by a booster dose. The study showed that PCV20 had numerically \nlower immune responses compared with PCV13 for most of the 13 shared serotypes. Post -dose \n3, PCV20 did not meet the non- inferiority criteria compared with PCV13 for some serotypes for \nthe primary immunogenicity outcome. Post -dose 4, PCV20 met the non- inferiority criteria \ncompared with PCV13 for all 13 shared serotypes and for all 7 additional serotypes. Evidence of \nharms was informed by findings from 3 RCTs .27 Across the 3 studies, SAEs were reported in \n4.5% of the PCV20 recipients compared with 3.7% of the PCV13 recipients, but none were \nconsidered to be vaccine -related. \nThe overall certainty of evidence was moderate. Certainty of evidence for benefits was \ndowngraded since these are immunogenicity studies and there are no correlates of protection \nestablished for most outcomes of interest. For harms, certainty of evidence was downgraded for \nimprecision due to lack of vaccine- related SAEs being reported. The WG determined that the \ndesirable anticipated effects of PCV20 were moderate. PCV20 provides the broadest serotype \ncoverage among available PCVs, so it is expected to prevent more disease. However, it is \nunknown how substantial the protection conferred from PCV20 will be based on available data. \nThe undesirable anticipated effects were considered to be minimal. The WG’s interpretation of \nwhether the desirable effects outweigh the undesirable effects was split between “favors \nintervention ” of PCV20 use and “favors both ” the intervention and the compar ator of either \nPCV13 or PCV15 use. Those who favor ed the intervention believe that PCV20 is expected to \nprevent more disease compared with current PCVs. Those who favor ed both consider ed the \nuncertainties of the clinical implications of the lower immunogenicity of PCV20 and improved \nimmunogenicity of PCV15 against serotype 3 compared with PCV13. \n22 Marra et al. Value Health 2022 \n23 Fiore et al. EID 1999 \n24 Veenhoven et al. Lancet 2003; and Van Kempen et al. Int J Pediatr Otorhinolaryngol 2006 \n25 The search strategy and search terms used are available in the supplementary slides from this presentation \n26 Senders et al. PIDJ 2021; and Pfizer unpublished data from B7471011 \n27 Senders et al. PIDJ 2021; Pfizer B7471011, unpublished data; Pfizer B7471013, unpublished data, limited to US and Puerto Rico \nsites \n53 \n \n   \n       \n  \n   \n    \n      \n   \n   \n  \n \n   \n   \n    \n    \n     \n    \n   \n  \n   \n    \n  \n  \n  \n \n    \n  \n  \n    \n    \n \n    \n     \n      \n   \n   \n \n    \n       \n  \n   \n  \n   \n   \n \n \n  \n \n  \n    \n         Findings from the pediatric PCV15 immunogenicity studies were presented during the February \n2022 ACIP meeting.28 No studies were conducted among children 2─ 18 years of age with \nunderlying medical conditions . Evidence on benefits was informed by 1 Phase 3 non -\nrandomized clinical trial with no comparator that evaluated the safety and immunogenicity of \nPCV20 use in healthy children 15 m onths ─17 years of age. This included children <5 years of \nage who received at least 3 doses of PCV13. All participants received a dose of PCV20. The \nstudy showed that PCV20 was immunogenic for all 20 vaccine serotypes when assessed 1 \nmonth after vaccination compared with pre- vaccination baseline. SAEs after vaccination was \nreported in 0.6% of the participants and none were considered to be vaccine- related. \nThe overall certainty of evidence was very low. Certainty of evidence was downgraded furthe r \nfor this study since this was an open -label non- randomized controlled trial with no comparator \ngroup and did not include children with underlying conditions. The WG determined that the \ndesirable anticipated effects of PCV20 use were moderate, the reasons for which were similar \nto those for routine use for children <2 years of age. In addition, there are no data on PCV20 \nuse among children with underlying medical conditions. The undesirable anticipated effects \nwere considered to be minimal. The WG’s interpretation of whether the desirable effects \noutweigh the undesirable effects was split between “ favors intervention” of PCV20 use and \n“favors both ” the intervention and the comparator of PPSV23 use after currently recommended \nPCV doses. Those who favored the intervention believed that PCV20 is expected to prevent \nmore disease compared with current recommendations. Those who favored both consider ed the \nfact that there are no data on PCV20 use in this population and that the clinical implications of \nimproved immunogenicity of PCV15 against serotype 3 compared with PCV13 are unknown. \nFor the E quity domain, data were reviewed of estimated pneumococcal conjugate vaccine \ncoverage by 24 months of age among children born during 2018─ 2019 by health insurance \nstatus using data from the National Immunization Survey -Child (NIS-Child) . Compared with \ncoverage among children with private insurance only, children who were uninsured and those \ninsured by Medicaid and other insurance was lower. Nationally representative PPSV23 vaccine \ncoverage data among children with indications are limited. In a study among children enrolled in the Michigan Medicaid program,\n29 64% of children with sickle cell anemia received 4 doses of \nPCV followed by a dose of PPSV23 as recommended by 5 years of age and 53% received 4 \ndoses of PCV followed by 2 doses of PPSV23 as recommended by 10 years of age . Other \nstudies that assessed PPSV23 coverage among children with underlying medical conditions \nwere much lower, ranging from 20% t o 40%.30 \nAn unpublished analysis using CDC ’s ABCs data assessed the incidence rate difference of IPD \namong children ≤17 years of age in the highest and the lowest Census tract poverty categories \nby year for all serotypes, PCV13 serotypes, PCV15/ non-PCV13 serotypes, PCV20/n on-PCV13 \nserotypes, PCV20 /non-PCV15 serotypes, and non- vaccine serotypes from 2010─ 2019. For all \nserotypes in PCV13 serotypes, incidence rate difference decreased after 2010 after PCV13 was recommended for use in children. There was essentially no incidence rate difference for \nPCV15 /non-PCV13 serotypes in 2018─ 2019. The IPD incidence rate difference for the \nadditional serotypes contained in PCV20 remained, and there was a slightly larger incidence \nrate difference for non -vaccine serotypes. \n28 Banniettis. \n…[truncated]", "summary": "MEETING OF THE ADVISORY  COMMITTEE ON IMMUNIZATION  PRACTICES (ACIP)  FEBRUARY 22 -24, 2023  MEETING SUMMARY  CONTENTS   WEDNESDAY: FEBRUARY 22, 2023 .......................................................................................................... 5  WELCOME AND INTRODUCTIONS ...................................................................................... 5  Call to Order/Roll Call…", "source_url": "https://www.cdc.gov/acip/meetings/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/minutes/summary-2023-02-23-24-508.pdf", "doc_date": "2023-02-23", "case": "acip", "sub_case": "minutes", "tags": ["acip", "cdc", "vaccines", "minutes"], "page_count": 199}
{"title": "Policies Procedures 508", "content": "Advisory Committee on Immunization \nPractices Policies and Procedures  \n \nJune 2022  \n \ni \n  \nContents  \nIntroduction  ................................ ................................ ................................ ................................ ..................  1 \nOrganization of this Document  ................................ ................................ ................................ .................  1 \nACIP Structure  ................................ ................................ ................................ ................................ ...............  1 \nCharge to Members  ................................ ................................ ................................ ................................ .. 1 \nMember Types  ................................ ................................ ................................ ................................ ..........  2 \nVoting Members  ................................ ................................ ................................ ................................ ... 2 \nEx Officio  and Liaison Members  ................................ ................................ ................................ ............  3 \nACIP Leadership  ................................ ................................ ................................ ................................ ........  3 \nChairmanship a nd Vice Chairmanship  ................................ ................................ ................................ .. 3 \nACIP Secretariat and Steering Committee  ................................ ................................ ............................  3 \nWork Groups  ................................ ................................ ................................ ................................ .............  4 \nACIP Functions  ................................ ................................ ................................ ................................ ..............  4 \nProcess for Developing Recommendations  ................................ ................................ ..............................  5 \nTechnical Aspects  ................................ ................................ ................................ ................................ .. 5 \nDeveloping the Recommendations  ................................ ................................ ................................ .......  5 \nMeetings  ................................ ................................ ................................ ................................ ...................  7 \nSelection of Topics  ................................ ................................ ................................ ................................  7 \nVoting  ................................ ................................ ................................ ................................ ....................  7 \nInternal Decision Memos  ................................ ................................ ................................ ......................  8 \nPublication of Recommendations  ................................ ................................ ................................ .........  9 \nImplementation and Evaluation of the Recommendations  ................................ ................................ .. 9 \nPublic Comment  ................................ ................................ ................................ ................................ .... 9 \nRules of Conduct for ACIP Meetings  ................................ ................................ ................................ ... 10 \nElectronic Recording by Public Media  ................................ ................................ ................................ . 11 \nACIP Recommendations for the Vaccines for Children (VFC) Program  ................................ ..................  11 \nMember Roles and Responsibilities  ................................ ................................ ................................ ............  11 \nGeneral Member Responsibilities  ................................ ................................ ................................ ...........  11 \nAttendance at Meetings  ................................ ................................ ................................ .....................  11 \n \nii \n  ACIP -Related Contacts  ................................ ................................ ................................ ........................  12 \nMedia Interactio n ................................ ................................ ................................ ...............................  12 \nCommittee Correspondence  ................................ ................................ ................................ ...............  13 \nResponsibilities Specific to Member Roles  ................................ ................................ .............................  13 \nChair  ................................ ................................ ................................ ................................ ....................  13 \nVice Chair  ................................ ................................ ................................ ................................ ............  14 \nVoting Members (including Chair an d Vice Chair)  ................................ ................................ ..............  14 \nConflicts of Interest when Participating as a Member  ................................ ................................ ...........  14 \nMembership Policies and Procedures  ................................ ................................ ................................ ........  16 \nVoting Members  ................................ ................................ ................................ ................................ ..... 16 \nAppointments a nd Tenure  ................................ ................................ ................................ ......................  16 \nNew Members ................................ ................................ ................................ ................................ .........  16 \nMembership Qualifications  ................................ ................................ ................................ .................  16 \nSolicitation for Nominees ................................ ................................ ................................ ....................  16 \nSelection of Nominees  ................................ ................................ ................................ ........................  16 \nNotification to Applicants  ................................ ................................ ................................ ...................  17 \nConsideration for Nomination: Financial Conflicts of Interest  ................................ ...........................  17 \nOrientation and Education  ................................ ................................ ................................ ......................  18 \nTable. ACIP Membership (as of October 2017)  ................................ ................................ ..........................  19 \nAppendix. Member Conflicts of Interest and Financial  Interests  ................................ ...............................  21 \n \n \n1 \n Introduction   \nThe Advisory Committee on Immunization Practices (ACIP) is a  federal advisory committee, composed  of \nmedical and public health experts , that provides advice and guidance to the Director of the  Centers for Disease \nControl and Prevention (CDC)  on the most effective means to prevent vaccine -preventable diseases  in the \nUnited States . ACIP’s  guidance includes  the use of vaccines , and may  also include recommendations for \nadministration of immune globulin preparations and/or antimicrobial therapy shown to be effective in \ncontrolling a disease for which a vaccine is available.  In addition, ACIP has a statutory authority for the Vaccines \nfor Children (VFC) program; ACIP has sole responsibility and authority to determine the vaccines, number of \ndoses, sched ule and contraindications for the VFC program.  \nACIP develops written recommendations —subject to the approval of the  CDC Director —for the routine \nadministration of vaccines to  both  pediatric and adult populations. To inform its advice to the CDC Director, ACIP \nconsiders disease epidemiology and burden of disease, vaccine efficacy and effectiveness, vaccine safety, the \nquality of evidence reviewed, economic analyses , and implementati on issues. The overall goals of ACIP are to \nprovide advice that will assist CDC and HHS in reducing the incidence of vaccine preventable diseases  and to \nincrease the safe usage of vaccines and related biological products, including active and passive \nimmun oprophylaxis. The target populations for ACIP recommendations are public and private health care \nproviders who administer vaccines, public and private officials who make vaccine policy, and the general public.  \nOrganization of this Document  \nThis document is  intended to serve as a reference for ACIP members (and interested members of the general \npublic ) about ACIP’s structure and functions. It is organized into the following sections:  \n• ACIP Structure : This section describes the individuals and groups who make up ACIP.  \n• ACIP Functions : This section provides an overview of the activities and objectives of ACIP.  \n• ACIP Roles and Responsibilities : This section contains descriptions of the roles and responsibilities of \nACIP members in carrying out ACIP’s functions.  \n• ACIP Membership Procedures: This section details the process for nomination, selection, and orientation \nof new ACIP members.  \nACIP Structure  \nACIP is a Federal Advisory Committee; t he Federal Advisory Committee Act of 1972 requires all such committees \nto have a committee charter.  The charter marks the formal establishment of the committee , and t he language of \nthe charter specifies the committee’s mission or charge and includes operat ional characteristics, such as the \nnumber of members and the types of expertise required, the number of meetings to be held per year, and the \nprojected yearly operating cost for the committee.  Any proposed changes to the charter are discussed by the \nSteeri ng Committee.  The ACIP Secretariat is responsible for renewing the charter every 2 years, and submitting \namendments  to the Secretary of Health and Human Services, who is responsible for reviewing and approving the \ncharter renewal .  \nACIP ’s charter is availa ble at https://www.cdc.gov/vaccines/acip/committee/charter.html .  \nCharge to Members  \nWithin ACIP’s charter, the formal Objective and Scope of Activities  are: \n \n2 \n “The Secretary, Department of Health and Human Services (HHS), and by delegation the \nDirector, Centers for Disease Control and Prevention (CDC), are authorized under Section 311 and \nSection 317 of the Public Health Service Act, [42 U.S.C. §243 and 42 U.S.C. §247b], as ame nded, \nto assist states and their political subdivisions in the prevention and control of communicable \ndiseases; to advise the states on matters relating to the preservation and improvement of the \npublic’s health; and to make grants to states and, in consul tation with the state health \nauthorities, to agencies and political subdivisions of states to assist in meeting the costs of \ncommunicable disease control programs.”  \nMembers of ACIP have a responsibility to provide CDC and HHS with high  quality , well consid ered advice and \nrecommendations . ACIP m embers play a critical role in ensuring the reputation of ACIP as a nationally and \ninternationally recognized advisory group in the field of immunization. ACIP members are committed to the \ndevelopment and improvement of public health policies.  \nMember Types  \nACIP comprises up to 20  voting members, eight ex officio  members, and 3 1 liaison representatives ( see the \nTable) , who function under  a Chair and Vice Chair and are guided by a Steering Committee .  \nACIP Membership must include at least 20% minority representation. The following is the official description of \nqualifying U.S. minority group candidates provided by Federal Advisory Committee Management Branch  \n(FACMB )/Management Analysis and Services Office  (MASO ): \n• Black or African American  \n• Hispanic  \n• American Indian/Alaska native  \n• Asian ( origins in any of the original peoples of the Far East, Southeast Asia, or the Indian subcontinent \nincluding, for example, Cambodia, China, India, Japan, Korea, Malaysia, Pakistan, th e Philippine Islands, \nThailand, and Vietnam. It includes “Asian Indian, ” “Chinese ,” “Filipino ,” “Korean ,” “Japanese ,” \n“Vietnamese ,” and “Other Asian .”) \nVoting Members  \nVoting members serve overlapping terms of 4 years . Voting members  are identified by the ACIP Steering \nCommittee, and selected and appointed by the Secretary  of HHS . Members fall into the following two \ncategories:  \n• Medical Professional Members ( up to 19). ACIP includes up to 19  members representing clinical \nmedical fields (physician, nurse, nurse practitioner) and/or public health professionals, e.g., State Health \nDepartment  staff or  epidemiologist s. These positions are held by technically qualified people trained in a \nclinical medical field who  possess in -depth knowledge of vaccines and immunization. Candidates for this \nposition may be recommended by a professional medical organization or other interested parties. ACIP \nalso welcomes self -nominated candidates possessing the requi red technical knowledge and experience.  \n• Lay Member: Consumer Representative (one) . ACIP must include a consumer representative as one of \nthe 15 voting members of the committee. This position is held by a technically qualified person \nknowledgeable about co nsumer perspectives and/or social and community aspects of immunization \nprograms. Candidates for this position may be recommended by a consortium of consumer -oriented \n \n3 \n organizations, an individual consumer -oriented organization, or other interested parties.  ACIP also \nwelcomes self -nominated candidates possessing the required technical knowledge and experience.  \nEx Officio  and Liaison Members  \nIn addition to the voting members, the Committee has  eight  ex officio  members (who generally do not vote, but \nmay be designated to vote in specific circumstances by the Executive Secretary) from other federal agencies and \n31 non-voting liaison representatives from professional societies and organizations responsible for the  \ndevelopment and execution of immunization programs for children and adults.  Ex officio  members and liaison \nrepresentatives are expected to represent the position and views of their sponsoring organizations , and to \ncontribute to Committee discussions when issues of importance to their organization are being discussed and \nwhen they possess information important to the discussion . Ex officio  and liaison members  also may serve o n \nWork Groups to provide expert advice and apprise the Work Group of the position t heir organization endorses.   \nEx officio  members representing (and financially supported by) other federal agencies/ departments are \nappointed based on a written document which outlines how the other agency/ department can contribute to the \nquality of ACIP de liberations and decisions and/or enhance the implementation of ACIP recommendations.  \nAppointments of liaison representatives, primarily from professional organizations, are based upon written \nrequests from organizations which document the commitment of the  organization to providing expert input into \nACIP decision -making process, travel and per diem support to their representative, and strongly encouraging \ntheir membership to adopt ACIP recommendations.  Because of space and time limitations at meetings, liai son \nrepresentatives must represent organizations that have broad immunization interests and that represent large \nconstituencies.  Groups that  represent more narrow interests (e.g., interest in a single disease or vaccine) or \nsmall constituencies (e.g., orga n transplant patients) are invited to participate in ACIP activities on an ad hoc \nbasis whenever issues of interest and concern are being discussed rather than requesting liaison representation.  \nACIP Leadership  \nChairmanship and Vice Chairmanship  \nEvery 3 years the ACIP Secretariat  identifies an ACIP Chair  from the ACIP member s who have served  at least one \nyear .  The ACIP Chair  serves a 3 -year term , as defined in ACIP Charter, and must be confirmed by the Secretary  \nof HHS when the nomination package is submitted for approval. The ACIP Secretariat  review s characteristics of \npotential candidates, including leadership skills , a demonstrated ability to maintain  a smooth and timely \nprocessing of agenda items and discussion by ACIP members and the public during ACIP meetings, and ability to \nmeet the other considerable demands placed on the Chair . \nThe ACIP Secretariat select s a voting member to serve as Vice  Chair of the Committee. This is not a position \nformally described within ACIP charter, but this is quite often the person who will be invited  to be come  the next \nChair.  \nACIP Secretariat and Steering Committee  \nThe ACIP  Secretariat is composed of CDC staff members . The ACIP Executive Secretary, or “Designated \nFederal Official,” (DFO) is a senior consultant to the Director of the National Center for Immunization and \nRespiratory Diseases (NCIRD). The DFO is responsible for the committee's overall management an d \ncompliance with FACA law.  \n \n4 \n Steering Committee m ember s includes representatives from each of the major centers at CDC. Some  Steering \nCommittee members  are affiliates of Work Groups within ACIP.  The Steering Committee meets four times per \nyear : once before each ACIP meeting (February, June, and October ) to plan the meeting agenda and once in \nNovember/December to discuss the nomination of new members.  \nWork Groups   \nACIP utilizes subgroups of the Committee, or Work Groups, to extensively  review  relevant published and \nunpublished data and develop recommendation options for presentation to the ACIP  during its public meetings .   \nACIP  Work Groups 1) must include two or more ACIP voting members , one of whom serves as Chair ; 2) must \ninclude CDC staff membe rs; 3) should include an FDA staff member , if appropriate ; and 4) may include ex officio  \nmembers and liaison representatives.  Only appointed ACIP voting members may chair a Work Group.  On \noccasion, disease/vaccine experts who are not government employees, ACIP members, ex officio  members or \nliaison representatives may be asked to serve as consultants to a Work Group.  Members with a potential \nfinancial conflict of interest cannot serve on  a Work Group that  is dealing with a product that  is the subject of \nthe conflict.  If the individual has unique expertise to the Work Group, that person may serve as a scientific \nconsultant but should not participate in policy deliberations.  Conflict of int erest declarations are signed by Work \nGroup members annually and changes should be announced during Work Group teleconferences.  \nRepresentatives of vaccine manufacturers may not serve as members of a Work Group but, at the discretion of \nthe Chair, may be as ked to make presentations to the group and answer questions.  Following these \npresentations, non -Work Group members may be asked to leave in order to allow deliberations to be limited to \nmembers of the Work Group.   \nACIP Work Groups accomplish most of their work through regular teleconferences.  These teleconferences  \nare closed  meetings, and therefore ACIP Work Groups must observe certain guidelines that allow them to \nfunction exempt from FACA requirements.   As FACA -exempt groups, ACIP W ork Groups  are not al lowed \nto render consensus advice or recommendations directly to  the Federal government. ACIP Work Group \nChairs, other Work Group  representatives, or the W ork Group s per se are not empowered to speak on \nbehalf of ACIP. Rather, they are utilized by ACIP to g ather and organize information upon which ACIP can \ndeliberate and act. Thus, while ACIP Work Groups  can and should examine specific topics in detail and \ndefine the issues, including development of options for recommendations, the actual processes of group \ndeliberation terminating in development of immunization recommendations must occur in the open \npublic forum of ACIP meetings in compliance with FACA requirements. Additional information on ACIP \nWork Groups and their functioning is available in the ACIP Wor k Group Standard Operating Procedures \ndocument, which is available from the ACIP Secretariat.   \nACIP Functions  \nPer its charter, ACIP’s primary duties are:  \n• Advising and guiding the Director of the CDC regarding use of vaccines and related agents for effectiv e \ncontrol of vaccine -preventable diseases in the civilian population of the United States. \nRecommendations made by ACIP are reviewed by the CDC Director, and if adopted, are published as \nofficial CDC/HHS recommendations in the Morbidity and Mortality Weekly Report  (MMWR ).  \n \n5 \n • Providing advice regarding the control of diseases for which a vaccine is licensed in the U.S. The \nguidance will address use of vaccines and may include recommendations for administration of immune \nglobulin preparations and /or antimicrobial therapy shown to be effective in controlling a disease for \nwhich a vaccine is available. The committee also may provide recommendations that address the \ngeneral use of vaccines and immune globulin preparations as a class of biologic agent s, use of specific \nantibo dy products  for prevention of infectious diseases, and special si tuations or p opulations that m ay \nwarrant modi fication of the r outine rec ommendations .  \n• Establish ing and periodically review ing and, as appropriate, revis ing the list of vaccines for \nadministration to children and adolescents eligible to receive vaccines through the Vaccines for Children \nProgram, along with schedules regarding the appropr iate dose and dosing interval, and \ncontraindications to administration of the pediatric vaccines , in accordance with Section 1928 of the \nSocial Security Act . \nThe specific functions that support these duties are detailed below.  \nProcess for Developing Recomm endations  \nTechnical Aspects  \nACIP Work Groups are formed to extensively  review  relevant published and unpublished data and develop \nrecommendation options for presentation to the ACIP  during its public meetings .  Additional information on \nACIP Work Groups an d their functioning is available in the ACIP Work Group Standard Operating Procedures \ndocument, which is available from the ACIP Secretariat.    \nWork Group are formed when updates to existing recommendations are anticipated based on availability \nof new data (regarding safety, effectiveness, and/or programmatic issues, e.g., vaccine administration or \nstorage), or licensure of a new vaccine or new indications for existing vaccines are anticipated. In general, \nWork Group s should begin re viewing data 12 -18 months prior to a potential decision on licensure; the \nlength of time required for the W ork Group  to review data in anticipation of vaccine licensure will depend \nupon the complexity of the topic and the amount of available data existing.  Immunoglobulin therapies \nand/or antimicrobial agents may be considered by ACIP in relation to control of a disease for which there \nis a vaccine available or under consideration.   \nActive Work Groups review recommendations regularly.  For vaccines for which there is not a Work Group, the \nrecommendations should be reviewed on a regular basis, at least every 7 years , and either revised, renewed, or \nretired  with a vote by ACIP . A Work Group may or may not be established for this review, depending on whether \nminor or major changes to the recommendations are needed.  However, a summary of any minor changes to the \nrecommendations is presented to ACIP and voted on and published in the MMWR . The adult schedule, child and \nadolescent schedule, and influenza recommendations are published in the MMWR  annually.  \nAll Work Group findings generally are presented to ACIP in an open meeting, and this information is then \ndeliberated.  ACIP Work Groups are u sed as a resource for gathering, analyzing, and preparing information for \nthe Committee that  will discuss and deliberate on the information presented .   \nDeveloping the Recommendations  \nRecommendations are subject to extensive review by  ACIP members,  staff o f the CDC  and FDA, outside expert \nconsultants, and vaccine manufacturers.  \n \n6 \n CDC vaccine recommendations are developed using an explicit evidence -based method based on the Grading of \nRecommendations, Assessment, Development and Evaluation (GRADE) approach. Ke y factors considered in \ndevelopment of recommendations include the balance of benefits and harms, type or quality of evidence, values \nand preferences of the people affected, implementation issues (excluding issues around payment and program \ncosts) and heal th economic analyses . More information about GRADE can be found in the ACIP’s GRADE \nhandbook ( https://www.cdc.gov/vaccines/acip/recs/grade/downloads/handbook.pdf ).  \nMost is sues that ACIP will vote upon require a GRADE evaluation of the evidence. However, a “when to GRADE” \nalgorithm is currently under development and once it is finalized a link will be added here. A summary of the \nGRADE evidence should be included in the MMWR  Policy Note, and the GRADE evidence tables are published on \nthe ACIP website ( https://www.cdc.gov/vaccines/acip/recs/grade/table -refs.html ). If it is determined that a \nGRADE eval uation is not needed, the rationale for why GRADE is not being done will be clearly documented. The \nACIP Secretariat is available to assist with questions about GRADE.  \nAdditionally, the ACIP is currently evaluating adoption of an evidence to recommendatio ns framework. \nInformation about the framework will be added here when available.  \nThe ACIP also provides guidance for the development of health economics studies \n(https://www.cdc.gov/vaccines/acip/committee/guidance/economic -studies.html ). These procedures should be \nfollowed for economic analyses to be presented to the ACIP to ensure that economic data presented to the ACIP \nand its W ork Group s are uniform in presentat ion, understandable, and of the highest quality.  \nWork Groups review  all of  the relevant published and unpublished data , including GRADE and economic \nanalyses  and implementation considerations .  Additionally, Work Groups  should seek additional data that  may \nhave been overlooked;  make  corrections in data content, evaluate appropriateness of the interpretation of data, \nand critique and challenge expert opinions. Areas in need of additional research or data should be clearly  \nidentified  in presentations to the full ACIP,  and each statement should include a specific delineation of data \ngaps.   \nDuring ACIP’s decision making process the importance of the economic analyses and implementation \nconsiderations must be balanced, while a lso ensuring that the recommendations remain focused on the \nevidence base. Additionally, p ublic comments are solicited during the Committee meetings and are considered \nduring the decision making process.  \nProgram staff compile and organize comments received  and discuss them with the appropriate Work Group \nwhile redrafting recommendations.  The Chair of the Work Group is responsible for the final review of the draft \nrecommendations submitted for deliberation and approval by the full voting Committee.   \nDocument s and data which will be discussed at the meeting must be disseminated to the Committee in a timely \nmanner for the members to have the time to review the information and prepare for productive discussions.  It is \nthe responsibility of the presenters/authors  to meet the timelines set by the ACIP Secretariat . These timelines \nare generally set ten weeks in advance of the meeting.  Materials are sent electronically to the Committee \nmembers  via email or the ACIP SharePoint site  fourteen days prior to the meeting d ates.   \n \n7 \n Meetings  \nRegularly scheduled meetings are held three times a year, at the call of the Executive Secretary.  Meeting dates \nare announced 6 -12 months in advance.  Meeting dates and the location of the meetings are posted on ACIP ’s \nhome page shortly afte r the dates and location are selected.  At least 60 days prior to the meeting, the meeting \ndate, items to be discussed, and location are published in the Federal Register . Meetings traditionally are held in \nAtlanta, Georgia.  All regular meetings are live webcast, with instructions for accessing the webcast available on \nACIP website before the meeting. Except as noted otherwise in these policies and procedures, the Chair will use \nRoberts Rules of Order (Eleventh Edition) as a guide when conducting Comm ittee meetings.  \nIn exceptional circumstances, the Director  of CDC may call an emergency meeting of ACIP without prior notice, \nor with less than the usual 60-day notice in the Federal Register . If the notice cannot be published at least 60 \ndays prior to the  meeting, the Federal Register  announcement will include the reasons for providing less than 60 \ndays ’ notice, as provided under GSA regulations at 41 CFR § 102 -3.150(b).  If exigent circumstances make \npublication of the Federal Register  notice prior to the meeting impossible, the notice shall be published in the \nFederal Register  as soon as possible after the meeting.  In addition, under such circumstances, the agency shall \nutilize other appropriate mechanisms for providing notice of the meeting prior to its o ccurrence.  \nACIP meetings are generally open to the public for their entire duration.  However, there are or may be occasions \nwhen the nature of the information is such that a closed meeting is required.  Examples might include \ndiscussions of proprietary info rmation, information related to national security interests, or information related \nto personnel action within CDC.  Participants in closed sessions may be required to sign pledges of nondisclosure.  \nAll provisions of the Federal Advisory Committee Act and G overnment in the Sunshine Act regarding closed \nsessions will be followed.  \nSelection of Topics  \nPotential topics for ACIP consideration can be suggested by anyone, but are most often proposed by CDC \nprogram staff, FDA program staff, ACIP members, and vaccine  manufacturers.   \nApproximately ten weeks prior to an upcoming meeting, a memorandum requesting potential agenda items is \nsent to ACIP voting members, CDC and FDA staff. The person suggesting an agenda item is asked to specify the \ntopic to be on the agenda,  issues of concern, and specific questions to be addressed by ACIP. Agenda items are \naccepted for presentation by the Steering Committee.  The Executive Secretary has the authority to approve, \ndisapprove, or hold over to another meeting any agenda item subm itted for the agenda.   \nVoting   \nThe Committee shall not take a vote unless a quorum of more than half of the voting members is present.  \nWhenever eight or more members are not eligible to vote, the Executive Secretary or  his or her  designee  shall \nhave the authority to temporarily designate the ex officio  members as voting members.  A majority vote is \naccepted by the committee.  In the case of a tie vote, the Chair’s vote determines the final result.  \nEx officio  members are expected to announce any conflicts of interest prior to any voting to determine if they \ncan vote.  \nACIP is charged with providing advice and guidance regarding the use of vaccines and related agents (e.g., \nimmune globulin preparations and/or antimicrobial therapy shown to be effective in controlling a disease for \nwhich a vaccine is available) for the ci vilian population of the United States.   Upon the licensure of any vaccine \n \n8 \n or any new indication for a vaccine, the committee shall, as appropriate, consider the use of the vaccine at its \nnext regularly scheduled meeting.   If the committee does not make a recommendation at the committee’s first \nregularly scheduled meeting, the committee shall provide an update on the status of such committee’s review.  \nACIP should  vote to make new recommendations when:  \n• There are no existing recommendations (previously not -vaccine preventable)  \n• The vaccine product uses a novel adjuvant  \n• The vaccine protects against different, or additional, serotypes, serogroups, etc.  \n• The age indication, number and/or schedule of doses, or population under consideration differs from \nprevious AC IP recommendations  \n \nACIP does not need to vote on language for clinical guidance, but they can review CDC developed clinical \nguidance.    \nThe Committee shall not vote to recommend a vaccine prior to its licensure by the FDA, except where \nextraordinary circu mstances exist that require potential use of a vaccine under an Investigational New Drug \napplication /Emergency Use Authorization . The Chair may ask members for their individual opinions on vaccine \nrecommendations prior to licensure in order to gain a sense  of the Committee’s thinking to provide program \nstaff and Work Group members with direction in developing draft recommendations.  \nAll ACIP recommendations that are approved by the CDC Director are considered CDC policy once published in \nthe Morbidity and M ortality Weekly Report .  \nInternal Decision Memos  \nAfter ACIP recommendations have been submitted to the CDC Immediate Office of the Director (IOD), the CDC \nDirector may adopt or reject the recommendations.  The DFO prepares an internal decision memo addresse d to \nthe CDC Director and obtains the necessary CIO approvals.  Following these approvals, the DFO then submits this \ndecision memo to the CDC Director, on committee stationery, in a memo signed by ACIP Chair.  ACIP \nRecommendations should not be posted by CDC , even as \"provisional recommendations,” until the CDC Director \napproves adoption of these recommendations. If the CDC Director adopts the recommendation(s), the decision \nis documented on the internal decision memo.   \nIf the CDC Director disagrees with one or more of ACIP recommendations, the decision is documented on the \ninternal decision memo.  The DFO works with CIO leadership to draft a memo for ACIP to address the Director’s \nconcerns. The Secretariat  will obtain any OD clearances of the draft memo as well as the CDC Director’s \napproval.  If ACIP concurs with the CDC Director and issues modified recommendations, the Secretariat  proceed s \nwith CDC adopted recommendations (see above – Internal Decision Memo is approved ). If ACIP does not modify \nits recommen dations, a second internal decision memo is created to brief the Director on the committee’s \nrecommendations.  If the Director still disagrees with ACIP recommendations, the Secretariat , with assistance \nfrom the appropriate CIOs, drafts and publishes a F ederal Register Notice  with opportunity for 30 days public \ncomment  that articulates the Director’s views and proposed decision.  \n \n9 \n Publication of Recommendations  \nNew and revised recommendations, once approved by the CDC Director, are published in the MMWR as a p olicy \nnote.  Comprehensive updates to ACIP recommendations, usually summarizing multiple ACIP recommendations \nthat have been published over a period, are published in the MMWR  as Recommendations and Report s. \nImplementation and Evaluation of the Recommendati ons \nImplementation and evaluation of the impact of the recommendations is the responsibility of the relevant CDC \nprogram not ACIP.  However, CDC programs will periodically report information relevant to these activities to \nACIP and others who may be involve d in implementing the recommendation (e.g., managed care, private \npractitioners).  \nPublic Comment  \nACIP holds open discussions and reserves meeting time for public comment , which is welcomed as an essential \naspect of the Committee’s deliberations . Public co mment is specifically invited on matters related to the ACIP’s \nroles under the Vaccines for Children Program and the Affordable Care Act.  In addition, public comments can be \nmade on any topic relevant to the ACIP’s charge as listed in the committee’s Char ter. \nOral Public Comment Procedures  \nEach ACIP meeting will include at least 60 minutes of time for in -person oral public comment, as needed. The \noral public comment period will occur before any scheduled votes. Each speaker will be allotted 3 minutes to \npresent. Each speaker may only speak once per meeting unless invited by the ACIP Chair.  \nPriority will be given to individuals who submit a request to make an oral public comment before the meeting \nand according to the procedures and deadlines in the Federal  Register Notice announcing the ACIP meeting and \non the ACIP meeting information website.  \nCDC will assign each individual  who submitted a request to make an oral public comment a unique identifier \nnumber with no personally identifying information. After the deadline for submitting requests for oral public \ncomment has passed, the list of unique identifiers will be provided to  the Deputy ACIP Executive Secretary, who \nwill use a Microsoft Excel formula to randomize the list. The randomized list will then be used to determine the \norder of speakers.  \nIf more people request to make an oral public comment than can be reasonably accom modated during the \nallotted public comment period at an ACIP meeting, CDC will determine the number of speakers that can be \nreasonably accommodated in the designated oral public comment period and invite that number of speakers to \ncomment. CDC will use a l ottery system and allot time to speakers in the same order they appear in the \nrandomized list. CDC will not give preference to any individuals, organizations, or interests. For example, if CDC \ndetermines that 20 speakers can be reasonably accommodated duri ng the oral public comment session, the first \n20 individuals on the randomized list will be allotted time to speak, while the names after the first 20 will not be \nallotted a time for oral public comment at that meeting. Any member of the public may still s ubmit a written \ncomment according to the procedures described below.  \nCDC will send email notification to individuals who have been allotted a time to provide an oral public comment \nat an ACIP meeting. Individuals who have been allotted a time must visit t he CDC information desk at the \nmeeting and sign in. If an individual who has been allotted time to provide an oral public comment at an ACIP \n \n10 \n meeting is unable to speak at the meeting, CDC may allow another person to provide the oral public comment \non the i ndividual’s behalf. CDC will provide the procedures for this substitution, if applicable, in the email \nnotification to individuals when they are allotted a time to provide an oral public comment.  \nOn-site, in -person registration for oral public comment at the meeting will only be available if there is time \nremaining in the oral public comment session after all individuals who submitted a request to make an oral \ncomment before the meeting have had an opportunity to speak. There is no guarantee there will be an \nopportunity for on -site, in -person registration for oral public comment, and all individuals interested in making  \nan oral public comment are strongly encouraged to submit a request in advance of the meeting according to the \ninstructions in the Federal Register Notice and the ACIP meeting we bsite.   \nThe ACIP Chair or DFO will announce at the beginning of the meeting if on -site, in -person registration will be \navailable based on the number of speakers allotted to speak during the oral public comment period. If on -site, \nin-person registration is available, individuals must request an opportunity to speak according to the instructions \nprovided by the ACIP Chair or DFO at the beginning of the meeting. CDC will determine the order of speakers \naccording to the randomization process described above. If  more individuals request an opportunity to speak \nthan there is available time, CDC will conduct a lottery according to the process above.   \nIn addition to the procedures above, the ACIP Chair has discretion to invite individuals to make an oral public \ncom ment outside of the designated comment period when relevant to the deliberations of the ACIP.  \nWritten Public Comment Procedures  \nAny member of the public can submit a written public comment to ACIP. Written comments  will be accepted up \nto 48 hours followi ng the end of an ACIP meeting. Comments must be submitted using the Federal eRulemaking \nPortal: http://www.regulations.gov  using the docket number for the ACIP meeting provided in the Federal \nRegister Notice annou ncing the ACIP meeting and according to the instructions on regulations.gov. All relevant \ncomments received will be posted without change to http://regulations.gov , including any personal information \nprovided.  Comment s submitted by 72 hours before the meeting will be made available to ACIP members before \nthe meeting.  \n  \nRules of Conduct for ACIP Meetings  \n \n• An interested person who wishes to make an oral public comment during an ACIP meeting should  submit a \nrequest with CDC before the meeting according to the instructions in the Federal Register Notice. Those who \nhave not submitted a request before the meeting will only have an opportunity to speak as time permits or \nat the discretion of the Chair.  \n• Audience members may no t present comments or questions to the Committee unless recognized by the \nChair.  \n• Attendees may be subject to security screening, such as presenting identification, passing through metal \ndetectors, and inspection of briefcases, packages, and so on.  \n• Attendees at the meeting are asked to maintain order and not display behavior th at is disruptive to the \nmeeting.  \n \n11 \n • The ACIP Chair or Designated Federal Officer will note on the record any disruptive behavior and will ask the \nperson to cease the behavior or e lse leave the meeting room.  \n• Attendees are asked not to approach the ACIP table area before, during, or after the m eeting without \npermission from the  Designated Federal Officer/Executive Secretary.  \n \nElectronic Recording by Public Media  \nThe Federal Advisory Committee Act states that advisory committee meetings be open to the public to the \nextent allowed by law and physical environment.  The Chair and the Executive Secretary have the authority to \nregulate all aspects of the meetings, including electron ic coverage.  To ensure the meeting is conducted in a fair \nand expeditious manner, the Chair may restrict or deny use of electronic recording equipment.  Any member \nfinding lights or recording equipment disruptive to the conduct of business at the meeting sh ould inform the \nChair or Executive  Secretary.  Factors to guide the Chair in this determination include the potential for significant \ndisruption, prejudicial impact on the meeting, fairness, and impairment of a participant’s ability to make a \npresentation o r participate freely in discussion.  \nACIP Recommendations for the Vaccines for Children (VFC) Program  \nACIP recommendations for the VFC Program are developed and voted upon in a separate process, distinct from \nACIP recommendations, after vaccines are license d. This process is based upon the unique statutory authority \nfor the VFC program established by the Omnibus Budget Reconciliation Act of 1993 (42 U.S.C. §1396s).  This \nlegislation gave ACIP the responsibility and authority to determine the vaccines, number of doses, schedule and \ncontraindications for the VFC Program.  \nConsistency between ACIP recommendations and VFC resolutions is a high priority.  Routine recommendations \nand recommendations for individual clinical -decision making are included in VFC resolutio ns. In some situations, \nusually for ease of implementation, the VFC resolution can be broader than ACIP recommendation.   \nFor each vaccine considered for inclusion in the VFC program, written resolutions on the vaccine, schedule, \ndose, contraindications, an d other issues relevant to appropriate uses of vaccines are reviewed by the \nCommittee and are adopted or rejected through votes by voting ACIP members.  A record of issues voted on is \nmaintained at CDC by ACIP Executive Secretary, and the requirements of ap proved VFC resolutions are \ncommunicated to VFC providers through the state immunization programs.  \nMember Roles and Responsibilities  \nGeneral Member Responsibilities  \nAttendance at Meetings  \nAt public meetings of ACIP, the voting members vote on vaccine rec ommendations. Recommendations are \naccepted by majority voting. Votes are recorded and the vote tally is captured in ACIP meeting minutes, which \nare made available  to the public and posted on ACIP website. The committee is updated regularly following \nimplem entation of new vaccine recommendations on pertinent data such as post -licensure safety monitoring, \ndisease surveillance and outbreaks, and coverage.  \nACIP meeting dates are published approximately six months to one year in advance. Except in the event of an \nemergency, members of ACIP assume the responsibility of attending all meetings. At the discretion of the \n \n12 \n Executive Secretary, a member may be linked to a committee meeting by telephone or video conference, in \nwhich case his or her  presence shall count t oward the quorum. When a member does not attend a meeting or \nattends a portion of a meeting, the member is provided background material on the issues discussed, and is \nexpected to be prepared to fully participate in the next meeting. If a member finds it d ifficult to attend \nmeetings, he/she has the responsibility to resign from the Committee. This will allow for a new member to be \nappointed to carry out the term. Failure by a member to actively participate in the work of the committee, \nincluding through reg ular attendance at ACIP meetings, may result in a request by ACIP Executive Secretary to \nthe Secretary of Health and Human Services to declare the position vacant with replacement of the affected \nmember.  \nACIP -Related Contacts  \nACIP members may be solicited  to participate in consultations or surveys on vaccine issues that are addressed by \nACIP. ACIP members should not participate in such consultations or surveys if they are requested to participate \nbecause of their ACIP membership status.  \nThe Department’s St andards of Conduct prohibit \"speaking\" on matters related to an ACIP member’s official \nduties outside Committee or Work Group meetings. ACIP members are prohibited from receiving compensation \nfor any speech or publication in which the purpose is to report on the member’s work on ACIP. Voting members \nshould be concerned with, and should report to the Executive Secretary, any solicitation of information about \nthe Committee’s activities by persons not officially affiliated with the Committee.  \nMedia Interaction  \nAs a federal agency, CDC's advisory committee meetings generally are open to the public and the media.  \nTherefore, Commit tee members may be approached by the media for an unscheduled interview.  Members are \nnot obligated to give an interview to the press either at the time they are approached or at a later time.  \nMembers are free to give interviews and express their opinions, or the views of their employer, professional \norganization, etc., but should  have CDC approval to speak as an ACIP member on ACIP matters.  CDC offers the \nfollowing  guidance to members who receive CDC authorization to conduct an interview:  \n• ACIP members may c hoose to do media interviews with other ACIP members or CDC staff present and \nparticipating.  \n• Media inquiries or requests for interviews may be referred to the CDC Office of Health Communications’ \nrepresentative.  \n• To avoid the appearance of bias, ACIP member s shall not speak to the media about what they believe to \nbe a likely outcome on an ACIP vote, prior to that vote being finalized.  \n• Members may discuss ACIP public meetings and their personal views, but must not disclose any \nproprietary information.  \n• Members  are to be objective regarding issues brought before the Committee and should be aware that \nany strong public statements on Committee matters prior to  a Committee vote could affect their future \nparticipation in related meetings because of the appearance of  bias.  \n• Members should not speak to the press as representatives of either the Committee or the CDC, unless \nthe agency designates a member to speak for the Committee (e.g., the Chair).  \n \n13 \n • Only the topic of discussion should be made public from closed portions of Committee meetings. Prior \nto discussing any matter discussed in a closed session, the member should consult with the Executive \nSecretary or a knowledgeable CDC staff member.  \nCommittee Correspondence  \nAny correspondence (letter, fax, e -mail, etc.) should  be routed to the Committee Management Specialist for \nACIP who then consults with the Executive Secretary to determine who the most appropriate respondent is . In \nsome cases, the Chair of ACIP is the appropriate person; in other cases, it may be the Executi ve Secretary or \nother CDC official or it may be the Chair of a Work Group.  However, no member should reply to official \ncorrespondence without consulting the Executive Secretary.  The only exception to this rule is that all members \nare free to respond to que stions about established points of fact (e.g., meeting dates, citations for ACIP \nrecommendations, etc.).  \nResponsibilities Specific to Member Roles  \nChair  \n• Presides at all committee meetings and ensures that the agenda is adhered to as closely as possible. If it \nis necessary for the Chair to leave the meeting due to a conflict of interest, the Chair shall appoint the \nDFO, the Executive Secretary , or another committee member to preside. This i ncludes those meetings \nconducted in person at the CDC as well as those special meetings that are called on an ad hoc  basis and \nconducted via teleconference.  \n• Screens each voting ACIP member for conflicts of interest relevant to that vote  when a vote is to be \ntaken . \n• Ensures that all rules of order and conduct are maintained during each session of an ACIP meeting. \nWhen a committee member(s) is disqualified from participation in committee discussions, the Chair \nensures that the disqualified member does not participate and/or physically leaves the meeting room. In \naddition , the Chair ensures that the minutes and transcript clearly indicate that the member did not \nparticipate and/or was not present during the discussion.  \n• Calls on individuals for opinions and comments and terminates any discussion that is felt to be \nunnecessary.  \n• Calls for a motion to be made and to be seconded when voting is required; calls for a vote when the \nmotion has been made and seconded.  \n• Calls for a nd controls public participation during the open portion of a meeting.  \n• Certifies to the accuracy of the minutes of each committee meeting prior to their distribution.  \n• With ACIP Secretariat, determines the need for establishment of new Work Groups and disb anding of \nWork Groups when a Work Group has completed its tasks.  \n• Leads the administrative meetings that are conducted at each ACIP meeting, which include as \nparticipants the voting ACIP members and selected CDC staff members. With ACIP Secretariat, develop s \nthe agenda for ACIP administrative meetings.  \n• With ACIP Steering Committee, assists in the development of the draft agenda for each ACIP meeting.  \n• As required, meets with ACIP Secretariat between ACIP meetings to discuss topics pertinent to ACIP (for \nexamp le, need for a new Work Group; emerging issues such as interruptions in vaccine supply, \ndevelopment of influenza antiviral resistance, need to call an emergency ACIP meeting, new ACIP \ninitiatives, agenda for ACIP administrative meeting, etc.). Such meeting s generally are conducted via \n \n14 \n teleconference and are generally attended by ACIP Chair, Vice  Chair and ACIP Secretariat and others as \nneeded.  \n• Represents ACIP at key meetings of other Federal Advisory Committees. The Chair may designate an \nalternate to atten d a meeting on his/her behalf, usually ACIP Vice  Chair; if the Vice  Chair is unavailable, \nthe Chair may request that another voting ACIP member attend on his/her behalf. Participation in such \nmeetings is generally funded by ACIP/ CDC.  \nVice  Chair  \n• ACIP Chai r may call upon ACIP vice Chair to assist with any of the Chair’s roles and responsibilities, as \nrequired.  \n• In particular, the Chair and the Vice  Chair may wish to divide responsibility for attendance at ACIP -\nrelated meetings (such as other Federal Advisor y Committee meetings) that occur throughout the year.  \nVoting Members (including Chair and Vice  Chair)  \nThe Chair and members of the Committee play a critical role in ensuring the Committee’s continued standing as \na nationally and internationally recognized leading body in the field of immunization . ACIP members are \nexpected to  observe the highest standards of impartiality, integrity and objectivity in their  deliberations , and \nthat their  recommendations should be  driven by available scientific evidence. Membe rs of ACIP will:  \n• Be committed to continued development and improvement in this important area of public health . \n• Bring relevant experience to the Committee . \n• Contribute to the provision of high quality and considered public health advice to the CDC and DHHS . \n• Be expected to make a full and considered contribution to the work of the Committee and to contribute \nfully to the debate and to the decision -making processes . \n• Provide expert guidance when an issue that falls within their  particular area of expertise is u nder \ndiscussion . \n• Contribute to the debate in the capacity of a well -informed health professional when the issue does not \nfall within their  expertise . \n• Take into account  the need for and impact of vaccines, the quality and safety of vaccines and strategies \nto ensure that the greatest benefit can be obtained from the most appropriate use of vaccines . \n• Be prepared to respond quickly to interaction by e -mail . \n• Be prepared, as requested by the Secretariat, to attend and contribute to the work of one or more of \nACIP work groups, which report to ACIP, and to attend occasional meetings of other Federal Advisory \nCommittees on vaccines for which representation of ACIP wo uld be needed . \n• Be committed to declare all relevant interests. Any reported interest that could be perceived as a \npotential conflict of interest will be disclosed during public ACIP meetings and in written meeting \nminutes, which are posted on ACIP website.  \nAll members serve in their personal capacity and should refrain from promoting the policies and views and \nproducts of the organization/institution for which they work.  \nConflicts of Interest when Participating as a Member  \nUpon appointment , each voting memb er is required to file an Office of Government Ethics 450 form (OGE450 \nhttp://www.oge.gov/Forms -Library/OGE -Form -450--Confidential -Financial -Disclosure -Report/ ) and a \n \n15 \n Confidential Financial Disclosure Report, which is reviewed by ACIP Secretariat, the Fed eral Advisory Committee \nManagement Branch and the Office of General Counsel at CDC. CDC will individually evaluate and consider for \nwaiver the related financial interests of each ACIP member in accordance with the OGE regulations at 5 CFR \nParts 2635 and 26 40, in particular to determine whether the need for the individual’s services outweighs the \npotential for conflicts of interest created by the financial interests involved.  Taking into consideration the nature \nof ACIP, the types of expertise necessary to a ccomplish its purpose, the various ways in which vaccine expertise \nis developed, and the integrity of the advisory committee process, CDC will generally consider issuance of \nwaivers in specific situations as detailed in the Appendix.  \nConfidential Financial  Disclosure must be updated annually during a member’s term. At every ACIP meeting , the \nChair calls for conflict of interest disclosure from each voting member  at the opening of the meeting .  \nAdditionally, each voting member must declare any conflict of in terest related to a particular vote  prior to the \nvote  being  taken by ACIP. Any actual or perceived conflict of interests will be explored fully by the Secretariat, \nCDC’s Federal Advisory Committee Management Branch, and CDC legal counsel if necessary. Memb ers with \ndeclared interests will be asked to recuse themselves from participating in the discussion and decision  making of \nthe issues relating to that interest. A member who has any doubt as to whether he/she has an interest that \nshould be declared, or whe ther he/she should take part in the proceedings, should ask the Secretariat for \nguidance.  \nAs detailed below and  in the Appendix, ACIP members will have consented to the following requirements as a \ncondition of membership.  \n• No member, his or her  spouse, or a member of his or her  immediate family can be directly employed by \na vaccine manufacturer or its parent company.  \n• Members cannot hold stock in any vaccine manufacturer or its parent company in excess of the OGE de \nminimus  amounts . Members also agree that t hey, their spouse and minor children will not purchase \nsuch stock during their tenure on the committee.  \n• Members cannot be holders of or otherwise be entitled to royalties or other compensation for a patent \non a vaccine product or process, immunologic agen t, adjunct or preservative that can be used for a \nvaccine that may come before ACIP during the anticipated term of appointment under consideration.  \n• Members agree to resign any advisory or consulting roles, whether paid or unpaid, to a vaccine \nmanufacturer  (except participation in clinical trials or service on data monitoring boards) and to forego \nsuch consultation or membership on any vaccine manufacturer advisory committees (except \nparticipation in clinical trials or service on data monitoring boards), du ring his/her tenure on ACIP.  \n• Members forego solicitation or acceptance of funds from vaccine manufacturers on behalf of \nthemselves or others.  \n• During their tenure on ACIP, members do not serve as a paid litigation consultant or expert witness in \nlitigation involving a vaccine manufacturer.  \n• Members do not accept honoraria or travel reimbursement with a funding source from a vaccine \nmanufacturer for attendance at scientific meetings, with the exception that they may receive travel \nreimbursement for CME present ations where the source of funding is an unrestricted grant to the CME \nprovider by a vaccine manufacturer.  \n \n16 \n Membership Policies and Procedures  \nVoting Members  \nAppointment of ACIP members is made by the Secretary of Health and Human Services upon the proposal of the \nSteering Committee, but the Secretary may select members other than those recommended by the Steering \nCommittee. Members of ACIP are appointed to serve for a term of four years, which in general is not renewable.  \nAppointments and Tenure  \nMembers will be appointed for a term of four years, which typically begins on July 1 in the year of appointment. \nIn general, a member’s term may not be extended beyond four years, and appointment to a second term is not \nallowed. In cases when a new round of appointees has not been approved by the Secretary to begin their terms, \nexisting ACIP members may be asked to extend their terms until their replacements have been appointed.  \nThe Chair shall be appointed for a term of three years. The Chair is selected and  appointed by the Secretary, HHS \nfrom among voting ACIP members who have had at least two years of experience serving on ACIP and have \ndemonstrated the ability both to lead the work of similar bodies and to work effectively with CDC.  \nNew Members  \nMembership Qualifications  \nACIP members are acknowledged experts with an outstanding record of achievement in their own field s and an \nunderstanding of the immunization issues covered by ACIP. They have a responsibility to provide CDC with high \nquality, well -considered advice and recommendations on matters described in ACIP Charter.  \nSolicitation for Nominees  \nEach year, suggestions for members are sought from a variety of sources , including professional societies, \ncurrent and former ACIP members, vaccine manu facturers, and the general public.  During the year , suggestions \nfor membership to the Committee are received from various sources.  These submissions are compiled for \nconsideration along with those received from the solicitation.  When openings for membershi p occur, a \nsolicitation for nomin ations  will be posted on ACIP home page and published in the Federal Register . \nSelection of Nominees  \nA listing of individuals suggested for nomination to the Committee is prepared and forwarded to the Executive \nSecretary, A CIP, and Steering Committee members.  These individuals discuss the qualifications of the candidates \nand the expertise needed on the Committee to develop a slate of potential nominees.  Selected c andidates are \nthen contacted to determine their willingness to  serve on the Committee and to adhere to limitations in their \nfinancial relationships with vaccine manufacturers as described in this document.  \nAll appointed ACIP members become Special Government Employees, subject to the federal laws that prohibit \npartic ipation in matters in which they have a financial interest.  Candidates must agree to comply with ACIP \npolicies and procedures.  With concurrence from the candidate s, the slate of nominees is submitted to the \nDirector  of CDC for concurrence and authorization  to prepare the nomination package.  \nThe Director  of CDC approves the final nomination package , which is  then  submitted to the HHS Secretary . The \nSecretary is responsible for appoint ing the member(s) to the Committee , who may or may not be those \nnominated by CDC.  If an appointment is confirmed by the Secretary, the new member serves for a term of up to \nfour years.  A member who is unable to fulfill the full term on the Committee may resign by submitting a letter of \n \n17 \n resignation to the Executive Secretary.  If a member resigns, a new member is appointed to fill the remainder of \nthe unexpired term.  \nOnce the name of an individual is submitted as a possible nominee to the Committee, the name and information \nreceived on the ca ndidate is held and may reconsidered in a future year if that person expresses an interest in \ncontinuing to be considered . \nNotification to Applicants  \nOnce the nomination package is submitted , both applicants who have and have not been put forward are \nnotif ied. After  approv al, the Secretary of HHS sends letters of congratulation to those candidates accepted for \nservice on ACIP. The respondents return an attached form to indicate acceptance (or non -acceptance) of \nappointment.  \nOnce selection is finalized, cand idates who were not selected will be sent an official letter .  Candidates not \nselected may be reconsidered  for the following year.   \nConsideration for Nomination : Financial Conflicts of Interest  \nIn order to achieve the highest quality comprehensive recommen dations for administration of vaccines, it is \ncritical that individuals chosen for membership on  ACIP have significant vaccine and immunization expertise, \nincluding crosscutting  knowledge and experience in the various  aspects  of the immunization field.  Som e \nexpertise important to the committee can only be developed through working relationships with vaccine \nmanufacturers, which are in a position to be financially affected by many of the recommendations of ACIP.  \nFederal law (18 U.S.C. §208) prohibits federal  executive branch employees, including Special Government \nEmplo yees (e.g., members of Federal A dvisory Committees such as ACIP), from participating in matters in which, \nto their knowledge, they, their spouse, minor child, or organization has a financial interest.  CDC is sensitive to \nconcerns about potential conflicts of interest by members serving on ACIP, particularly given the substantial \nfinancial implications some ACIP recommendations may have for vaccine manufacturers.  Therefore, to assure \nthe integrity of the committee, CDC has taken steps to assure that there is not only technical compliance with \nthe ethics statutes and regulations regarding financial conflicts and the appearance of financial conflicts of \ninterest, but also that more gener al concerns regarding the potential for the appearance of a conflict are \naddressed, or avoided altogether, through both pre - and post -appointment considerations.  CDC has concluded \nthat particular interests create conflicts, or perceptions of conflicts, whi ch either contribute little or nothing to \nthe ongoing level of expertise required on the committee, or create an appearance of such a strong interest in \nthe success or failure of the products of a vaccine manufacturer, that such interests should disqualify  an \nindividual from membership on the committee.  These include:  \n• A person will be not be considered for membership if they, their spouse, or a member of their \nimmediate family is directly employed by a vaccine manufacturer or its parent company.  \n• Persons who  hold stock in any vaccine manufacturer or its parent company in excess of the Office of \nGovernment Ethics ( OGE ) de minimus  amounts will not be considered for nomination unless they agree \nto divest themselves of such stock before their term of office begin s and all nominees must agree that \nthey, their spouse and minor children will not purchase such stock during their tenure on the \ncommittee.  \n \n18 \n • A person will be not be considered for membership if that person is a holder of, or otherwise is entitled \nto royalt ies or other compensation for, a patent on a vaccine product or process, immunologic agent, \nadjunct or preservative that can be used for a vaccine that may come before ACIP during the anticipated \nterm of appointment under consideration.  \n• To be considered f or appointment to ACIP, a potential nominee must agree to resign any advisory or \nconsulting roles, whether paid or unpaid, to a vaccine manufacturer (except participation in clinical trials \nor service on data monitoring boards) and to forego such consultat ion or membership on any vaccine \nmanufacturer advisory committees (except participation in clinical trials or service on data monitoring \nboards), during his/her tenure on ACIP.  \n• Except as allowed under the previous bullet , potential nominees must agree that  during their tenure on \nACIP they will forego solicitation or acceptance of funds from vaccine manufacturers on behalf of \nthemselves or others (e.g., to support educational activities of their Department or an organization of \nwhich they are a member, offic er or employee).  \n• Potential nominees must agree that during their tenure on ACIP they will not serve as a paid litigation \nconsultant or expert witness in litigation involving a vaccine manufacturer.  \n• Potential nominees must agree that during their tenure on ACIP they will not accept honoraria or travel \nreimbursement with a funding source from a vaccine manufacturer for attendance at scientific \nmeetings, with the exception that they may receive travel reimbursement for CME presentations where \nthe source of fun ding is an unrestricted grant to the CME provider by a vaccine manufacturer.  \n \nOrientation and Education  \nOrientation for new members is provided to enable members to fully understand the work and functioning of \nACIP, including participation in ACIP work groups. This is typically offered as a two-hour  teleconference/webinar \nwithin one month of appointment of n ew members. The Secretariat will further arrange briefing and meetings \nwith CDC staff and any other training in order to facilitate the full engagement of new members in the work of \nACIP. From time to time, ACIP Secretariat arranges educational sessions on  topics such as the role of health \neconomics in development of ACIP recommendations, immunization safety monitoring and procedures used in \ndevelopment of evidence -based recommendations. These sessions are sometimes held at the CDC on the day \nbefore an ACIP  meeting.   \n \n19 \n  \nTable. ACIP Membership (as of June 2022 ) \nGroup  n Description of members  \nVoting members  ≤19 Subject matter experts in vaccinology, immunology, pediatrics, internal medicine, \nnursing, family medicine, virology, public health, infectious diseases, and/or \npreventive medicine  \n1 Consumer representative who provides perspectives on the social and community \naspects of vaccination.  \nEx officio  members \n(non -voting)  6 Individuals in the roles listed below or their designees.  \n• Director, Division of Vaccine Injury Compensation, Bureau of Health Professions, \nHealth Resources and Services Administration  \n• Director, Center for Biologics Evaluation and Research, Food and Drug \nAdministration  \n• Director, Center for Medicaid and State Operations, Centers for Medicare and \nMedicaid Services  \n• Director, Division of Microbiology and Infectious Diseases, National Institute of \nAllergy and Infectious Diseases, National Institutes of Health  \n• Director, Indian  Health Service  \n• Director, National Vaccine Program Office, HHS  \nLiaison representatives \nfrom professional \norganizations (non -\nvoting)  31 Participating organizations:  \n• American Academy of Family Physicians  \n• American Academy of Pediatrics  \n• American Academy of Ph ysician Assistants  \n• American College Health Association  \n• American College of Nurse Midwives  \n• American College of Obstetricians and Gynecologists  \n• American College of Physicians  \n• American Geriatrics Society;  \n• America’s Health Insurance Plans  \n• American Medical Association  \n• American Nurses Association  \n• American Osteopathic Association  \n• American Pharmacists Association  \n• Association of Immunization Managers  \n• Association for Prevention Teaching and Research  \n• Association of State and Territorial Health Officials  \n• Biotechnology Industry Organization  \n• Council of State and Territorial Epidemiologists  \n• Canadian National Advisory Committee on Immunization  \n• Infectious Diseases Society of America  \n• National Association of County and City Health Official  \n• National Association for Pediatric Nurse Practitioners  \n• National Foundation for Infectious Diseases  \n• National Immunization Council and Child Health Program, Mexico  \n• National Medical Association  \n• National Vaccine Advisory Committee  \n• Pediatric Infectious Diseases Society  \n \n20 \n   • Pharmaceutical R esearch Manufacturers of America  \n• Society for Adolescent Health and Medicine  \n• Society for Healthcare Epidemiology of America  \n \n \n21 \n Appendix . Member Conflicts of Interest and Financial Interests  \nACIP members must file Office of Government Ethics (OGE) Confidential Financial Disclosure Reports, Form 450, \nas required by OGE regulations and the CDC policy and the Financial Disclosure for Federal Advisory Committee \nMembers Appointed as Special Governm ent Employees.  CDC will individually evaluate and consider for waiver \nthe related financial interests of each ACIP member in accordance with the OGE regulations at 5 CFR Parts 2635 \nand 2640, in particular to determine whether the need for the individual’s services outweighs the potential for \nconflicts of interest created by the financial interests involved.  Taking into consideration the nature of  ACIP, the \ntypes of expertise necessary to accomplish its purpose, the various ways in which vaccine expertise is  \ndeveloped, and the integrity of the advisory committee process, CDC will generally consider issuance of waivers \nas follows:  \n1. Limited Waivers.  Where conflicts exist, only limited 208(b)(3) waivers will be considered, except as noted in \nnumber 6, below.  \n2. Scope of Limited Waivers.  Limited waivers will generally allow members to fully participate in committee \ndiscussions related to waived interests, with the condition that they will be prohibited from voting on such \nmatters (except in the case of de minimus  interests which do not disqualify a member from voting).  In addition, \nmembers will be prohibited from serving as chairs of subcommittees or Work Groups considering issues where \nconflicts exist.  \n3. Clinical Trials.  A member who is serving as a pri nciple investigator or as a member of a data monitoring board \non manufacturer -sponsored research will be considered for issuance of a limited 208(b)(3) waiver to serve as a \nconsultant to present to ACIP on matters related to this manufacturers’ vaccine, bu t cannot participate in \ndeliberations or vote on such issues.  The member may be granted a waiver as described in number 2, above, for \nissues related to other vaccines produced or marketed by that manufacturer.  \n4. Public Disclosure.  In order to assure that their fellow committee members and the public are aware of a \nmember’s related financial interests;  continued membership on the committee will be conditioned on the \nmember’s agreement to publicly disclose all vaccine -related interests and work, including pa rticipation in clinical \ntrials, at the beginning of each ACIP meeting.  \n5. Vaccine Stocks.  As provided in section B.1.b., except as allowed under OGE regulatory exemptions for de \nminimus  amounts, members must agree to not own vaccine stocks during their com mittee tenure.  In order to \navoid even the appearance of a conflict, ownership of any amount of vaccine stocks is discouraged.  Therefore, \nownership by the member, spouse or minor children of de minimus  amounts of stock in any vaccine \nmanufacturer or its par ent company must be disclosed at the beginning of each ACIP meeting.  \n6. Disclosure Not Required - Uncontrolled Interests.  The member's employing institution may have financial \ninterests which provide income to the member (e.g., grant funds deposited into a  common account), but which \ninterests are outside the member's area of work.  Such interests are considered outside the member's control, as \nare an employing institution’s financial interests that  do not provide income to the member.  Given the lack of \ncontr ol, those interests, if they may be imputed to the member under 208, will generally be waived under \n208(b)(3) and, if waived, are not required to be disclosed.  There are no restrictions on Committee activities \nbased on such waived interests.  \n \n22 \n 7. Tenure Comm itments.  Continuing membership on the committee and issuance and maintenance of any \nwaiver will also be conditioned on the member’s fulfillment of commitments noted in section B.1 regarding \ninterests during their tenure on the committee.", "summary": "Advisory Committee on Immunization  Practices Policies and Procedures     June 2022     i     Contents   Introduction  ................................ ................................ ................................ ................................ ..................  1  Organization of this Document  ................................ ................................ ................................ .................  1  ACIP Structure  ................................…", "source_url": "https://www.cdc.gov/acip/about/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/Policies-Procedures-508.pdf", "case": "acip", "sub_case": "other", "tags": ["acip", "cdc", "vaccines", "other"], "page_count": 25}
{"title": "Work Group Guidance 508", "content": "ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES : \nWORK GROUPS  \nStandard Operating Procedures: August 201 8 \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nAdvisory Committee on Immunization Practices Secretariat  \nCenters for Disease Control and Prevention  \n \n2 \n  \nContents  \nI. Overview of Advisory Committee on Immunization Practices Work Groups  ..... 2 \nII. Work Group Membership  ................................ ................................ ........................  4 \nIII. Roles and Responsibilities ................................ ................................ .........................  6 \nIV. Work Group Teleconferences and Meetings ................................ ...........................  8 \nV. Confidentiality  ................................ ................................ ................................ ...........  9 \nVI. Pharmaceutical Companies and Work Groups  ................................ ....................  10 \nVII.  Work Group Resources  ................................ ................................ ..........................  12 \nVIII.  Preparing for ACIP Meeting Presentations  ................................ ..........................  13 \nSubmitting Agenda Items for ACIP Meetings  ................................ ................................ ...... 13 \nACIP Briefing Do cuments  ................................ ................................ ................................ ...... 13 \nACIP Background Materials  ................................ ................................ ................................ .. 13 \nACIP Presentations  ................................ ................................ ................................ .................  14 \nIX. Evidence -Based Decision and Cost -effectiveness Analyses  ................................ .. 15 \nX. Preparing MMWR Reports  ................................ ................................ ....................  16 \nXI. Termination of Work Groups  ................................ ................................ ................  17 \nXII.  Appendices  ................................ ................................ ................................ ...............  18 \nAppendix 1 : Additional Information for FDA, ISO, and ISD Representatives to \nACIP WGs ................................ ................................ ................................ ................................  18 \n \nI. Overview  of Advisory Committee on Immunization Practices \nWork Groups  \nThe role of the Advisory Committee on Immunization Practices (ACIP) is to assist the \nCenters for Disease Control and Prevention (CDC) and the Department of Health and \nHuman Services (HHS) in developm ent of public policy related to immunization of the \ncivilian population in the United States. ACIP  utilizes subgroups of the Committee, known \nas work groups (WGs), to review  relevant published and unpublished data and develop \nrecommendation options for  presentation  to the ACIP . ACIP WGs are intended to augment \nthe effectiveness of ACIP.  The direction, focus , and pace of both ACIP and the individual \n \n3 \n WGs are guided by CDC and HHS priorities , and by the perceived need for expert advice to \ninform  developmen t of immunization policy.  \nACIP WGs  are responsible for collection, analysis , and preparation of information for \npresentation, discussion, deliberation , and vote by the ACIP in an open public forum. WGs \nreview specific topics in detail and elucidate issues  in a manner that facilitates informed \nand efficient decision making  by ACIP voting members .  \nFive WGs —the Adult Immunization, General Recommendations, Child/Adolescent \nImmunization, Evidence Based Recommendations, and Influenza  WGs —are permanent . \nThe remaining WGs are task oriented ; such t ask-oriented WGs are developed in response \nto specific needs and are disbanded when the task at hand has been completed. A list of  \nWGs that are currently active can be obtained from the ACIP Secretariat  or the ACIP \nwebsite . \nQ.: When is the appropriate tim e to establish  an ACIP WG?   \nA.: ACIP WGs should be established  when : \n•  Updates to existing recommendations are anticipated based on availability of new \ndata ( regarding safety, effectiveness, and/or programmatic  issues, e.g., vaccine \nadministration or storage ). \n• Licensure of a new vaccine or new indications for existing vaccines are anticipated.   \no In general, WGs should begin reviewing data 12 -18 months prior to a \npotential decision on licensure ; the le ngth  of time required for the WG to \nreview data in anticipation of vaccine licensure will depend upon the \ncomplexity of the topic, and the amount of available data  that exist s. \no Immunoglobulin therapies , monoclonal antibodies,  and/or antimicrobial \nagents may be considered by ACIP only in relation to control of a disease for \nwhich there is a vaccine av ailable or under consideration.   \n• Existing ACIP recommendations should be reviewed on a regular basis , at least \nevery 7 years, and either revised , renewed , or retired  with a vote  by ACIP.  The ACIP \nSecretariat will establish a WG if review of the recommendations identifies a need \nto revise  the recommendation s.  \nEach WG operates under specific Terms of Reference (TORs) determined by th e WG Chair  \n(see below ) and WG Lead  (see below ) at the time the WG is formed. The WG Chair and WG \nLead, in consultation with other CDC staff, should re-evaluate  the TOR s annually . TORs \nshould be formalized annually  to provide documentation of the WG priorities for each \n \n4 \n year.  TORs will be included on the ACIP website along with a listing of current WG \nmembers and will be updated annually.  \nTORs should be sent to potential WG members as the WG is being formed.  Addition ally, \nTORs should be included in the WG Chair presentation to ACIP annually to ensure \ntransparency.  Examples of WG TORs can be obtained from the ACIP secretariat. TORs \nshould be brief (<1 page) and include  the following sections:   \n• Purpose o f the WG  \n• Policy Topics Under Consideration by the WG  \n• WG Activities  \nQ.: How frequently should WG TORs be evaluated and/or updated?  \nA.: TORs  should be re -evaluated when major tasks are completed ; when the WG Chair or \nWG Lead change s; if new issues relevant to the WG arise ; when events result in shifts in \npublic heath priorities ; and annually  between the June and October ACIP meetings.  \nII. Work Group Membership  \nEach WG must include at least two voting members of ACIP , one of whom functions as WG \nChair . A CDC subject ma tter expert (SME) serves as WG Lead, and generally is selected by \nthe concerned CDC program . Other WG members may include ACIP ex-officio  members, \nACIP liaison representatives, and invited consultants. Most WGs should include a \nrepresentative from CDC’s Immunization Safety Office  and Immunization Services Division . \nCDC staff may serve in a supportive or administrative function. During ACIP meeting \npresentations, CDC staff should be listed on the WG membership slide separately from WG \nmembers.  \nWGs  are encouraged to invite a consumer representative to join as an expert consultant . \nAn ideal consumer representative has experience or expertise relevant to the vaccine, \ndisease  or condition involved . It is desirable, though not required, that the individual  have \nsome degree of familiarity with vaccines. The WG should have a reasonable expectation \nthat the candidate will be able to engage in a dispassionate, unbiased review of data and \nto comply strictly with the confidentiality requirements placed on all WG members. The \nACIP Secretariat can help identify potential consumer representatives.  \nIn order to facilitate participatory discussion among all WG members, consideration should \nbe given to the overall number of WG members, including the invited liaison \nrepre sentatives and consultants serving on the WG , and the expertise each invited \nconsultant brings to the WG. The recommended size of a WG is <15 members, not \n \n5 \n including CDC staff supporting the WG . WG members may change when the WG TORs  \nchange  and should be reassessed annually . \nRepresentatives of vaccine manufacturers may not serve as members of a WG but may , at \nthe discretion of the WG Chair and WG Lead, be invited  to make presentations to the \ngroup and answer questions.  Experts  from the private sector who do not represent vaccine \nmanufacturers may be asked to make presentations to the WGs or to participate in \ndiscussions at the discretion of the WG Chair and concur rence of WG Lead. Following these \npresentations, non -WG members are asked to leave so that deliberations are limited to \nmembers of the WG.  \nParticipants in WGs are typically limited to U .S. residents , due to the increased cost of \ninternational teleconferences, but exceptions occur when expertise is needed from \nindividuals living outside the U nited States . \nQ.: How are WG members selected?  \nA.: The process for WG member selection is as follows.  \n• The ACIP Secretariat  will, in consultation with the WG Lead,  recruit one ACIP voting \nmember to serve as WG Chair , and at least one additional ACIP voting member.  The \nACIP secretariat will send an inquiry  to all current voting ACIP members to assess \ninterest.  The ACIP voting members and WG Chair will be determined based on \ninterest, need for expertise on the WG, and balancing ACIP members ’ available \ntime.   \n• As an ACIP voting member’s term expires, the perso n may continue to serve on the \nWG in a consultant role at the discretion of the WG Chair and WG Lead.   \n• At the time new ACIP members begin their terms, the Secretariat will request a list \nof the WGs they are interested in joining and balance these requests with the need \nto fill voting member positions on WGs.  When feasible, the WG Chair will be \nreplaced by an ACIP voting member who has already been on the WG for a period of \ntime.  The WG Chair will be chosen by the WG Lead in consultation with the \noutgoing WG Chair , but should be approved by the Secretariat in order to ensure \nbalance of workload among ACIP voting members.  \n• The WG Lead will be designated by the CDC Center, Institute, or Office  with \nresponsibility for the concerned program/vaccine to be considered.  \n• The WG Chair and the WG Lead, in consultation with the ACIP Secretariat , will \nrecruit additional members and consultants for the WG. The WG Chair and the WG \nLead should work closely together to determine priorities, process, direction , and \ntimeline for WG activities, again in consultation with the ACIP Secretariat . \n \n6 \n • In consultation with the WG Lead and WG Chair, the ACIP Secretariat  will extend \ninvitations to those ex officio and liaison organizations  requested by the WG \nChair/ WG Lead for representation on the WG.  The organization or ex  officio agency \nwill designate the individual to represent the organization and agency and can \nrequest a n alternate . When determining the organizati ons and ex officio liaisons to \ninclude, the existing size of and the  relevance of the organization or ex officio \nbackground to the WG TOR s. There should be an FDA liaison for each WG where a \nnew vaccine or indication is under consideration by the WG.  \n• The W G Lead should  extend requests fo r subject matter experts to serve as \nconsultants to participate on  a WG  to ensure there is adequate expertise on the WG \nto provide evidence -based  information to support ACIP deliberations . Consultants \nshould serve as a resource to offer expertise on clinical, programmatic and basic \nscientific aspects of the vaccine -preventable disease and vaccine, and other factors . \nIf these individuals do not have a conflict of interest (see below), consult ants may \nparticipate in all discussions and deliberations. If a subject matter expert has a \nconflict of interest, he/she may participate in scientific discussions but may not \nparticipate in policy deliberations.  \n• A temporary consultant can be included in a WG to deal  with an important but \nlimited  policy topic (i.e., involving interpretation of information and policy \ndiscussion over a period of months) . \nIII. Roles and Responsibilities  \nWG Chair  \n• Signs annual membership agreement form  (see A ppendix  1). \n• Attends and participates in  WG meetings on a regular basis.  \n• Completes timely review of materials as requested.  \n• Works with the WG Lead to identify potential WG members . \n• Reviews WG membership to ensure necessary expertise  is represented . \n• Works with the WG L ead to set an agenda for WG meet ings and for timelines of \npresentations at the full ACIP meetings.  \n• Provides overview presentation of WG topics at ACIP meetings , and other \npresentations if needed . \n• Co-authors  Morbidity and Mortality Weekly Report (MMWR)  Policy Notes and \nRecommendations and Reports  (comprehensive ACIP recommendation document) .  \nACIP Member (s) \n \n7 \n • Signs annual membership agreement .  \n• Attends and participates in  WG meetings on a regular basis.  \n• Completes timely review of materials as requested.  \n• Co-authors  MMWR  Policy Notes and Recommendations and Reports  if authorship \ncriteria are met .  \nCDC WG Lead  \n• Works with WG Chair to identify potential WG members . \n• Works with the WG Chair to set an agenda for WG meetings and for timelines of \npresentations at ACIP meetings .  \n• Coordinates WG meeting s, documents roll call, takes minutes or designates \nanother person on the WG (e.g., other CDC staff member) to do so (see Work \nGroup Teleconferences and Meetings , below ). \n• Coordinates developing agenda proposals, background and briefing documents, \nand presentations on behalf of the WG for ACIP meeting s. \n• Leads development of MMWR Policy Notes and Recommendations and Reports  \ndocuments.  \n• Attends and participates in monthly WG Lead meetings, routinely uploads  \ndocuments to the ACIP SharePoint site, completes a timely review of materials , and \nresponds to requests from the ACIP Secretariat.  \n• Works with the Adult Immunization and Child/Adolescent Immunization WG Lead \nto rev iew immunization schedule footnotes annual ly. \nLiaison Representatives and Ex-Officio  Members  \n• Signs annual membership agreement  and conflict of interest  form s. \n• Attend s and participates in WG meetings on a regular basis . \n• Completes  timely review of materials as requested . \n• Communicate s the perspective  of the organization or agency  they  represent at WG \nmeetings . \n• Additional information for FDA representatives to ACIP WGs can be found in \nAppendix 2.  \nConsultants  \n• Signs annual membership agreement  and conflict of interest  form s.  \n• Attend s and participates in WG meetings on a regular basis . \n• Completes  timely review of materials as requested . \n• Serve s as a subject matter expert  during  WG meetings and calls . \n \n8 \n CDC Staff  \n• Provide administrative support and technical expertise to ACIP WGs.  \no CDC staff on WGs bring subject matter expertise and current professional \nfocus in areas relevant to the goals of the WG. CDC staff are aware of \nagency priorities, and of current and antici pated policy issues that may arise \nin association with the focus of each WG and are responsible for working \nwith the WG L ead to ensure that the focus, direction , and timing of WG \nefforts remain compatible with the needs of CDC and HHS.  \n• As needed, p erform,  coordinate, or identify scientific studies and outbreak \ninvestigations to address questions that arise regarding vaccine policy decisions; \nconduct analysis of data addressing efficacy, effectiveness, safety, feasibility, and \neconomic aspec ts of immunizati on policy ; and participate in evaluation of quality of \nthe evidence, e.g. GRADE review . \n• Additional information for ISO and ISD representatives to ACIP WGs can be found in \nAppendix 2.  \nIV. Work Group Teleconferences and Meetings  \nWGs accomplish most of their work  through teleconferences. When the group is active, a \nset day and time for routine monthly teleconferences (e.g., 2 PM EST on the last Friday of \nthe month) is usually established. This allows standing teleconferences to be arranged and \nWG members to anticipate and reserve time for these teleconferences. The frequency of \nWG teleconferences may change depending on the urgency of the issue (s) being \nconsidered by the group.  Most WGs meet once per month, but some WGs meet twice \nmonthly, particularly in the time period leading up to an ACIP meeting when the WG may \nneed to meet more frequently.  \nMost WG teleconferences are held using a call -in number or Skype business \nteleconfer ence  software , and are not operator assisted.  The same number may be used for \nall teleconferences for a particular WG.  Teleconferences should not be recorded .  \nThe development of a brief (1 -2 page) summary of each WG meeting will facilitate the \nfunction of  the WG; the taking of minutes is best accomplished by a WG member other \nthan the WG Chair or the WG Lead , in order to allow the WG Chair and WG Lead to lead \nand manage the meeting effectively. WG meeting minutes are confidential and may be \nshared by the W G Chair/ WG Lead  with WG members.  \nMinutes and slides from each WG teleconference should be uploaded to the ACIP \nSharePoint sites by the WG Lead on a regular basis (e.g., monthly or quarterly).  \n \n9 \n When needed, an in -person WG meeting may be arranged either immediately before or \nafter a full ACIP meeting.  The Secretariat cannot support these meetings  financially , but \nmay be able to reserve a room in the G lobal Conference Center  if a need is identified early.  \nIn-person meetings should be used with discr etion : ACIP  voting members should primarily \nfocus on the public meeting discussions.  Please consult with the Secretariat prior to \nscheduling an in -person WG meeting during an ACIP meeting.  \nQ.: Are there special considerations for WG meetings in relation to  FACA requirements?  \nA.: Yes. To be able to operate in closed meetings , ACIP WGs must observe certain guidelines \nthat allow them to function exempt from FACA requirements. ACIP WGs function in a fact -\nfinding role, do not include a quorum of voting ACIP memb ers, and do not vote on policy ; \nthey are therefore exempt from FACA requirements.  \nAs FACA -exempt groups, ACIP WGs are not allowed to render consensus advice or \nrecommendations directly to the Federal government. ACIP WG Chairs, other WG \nrepresentatives, or the WGs per se are not empowered to speak on behalf of ACIP. Rather, \nthey are uti lized by ACIP  to gather and organize information upon which ACIP  can \ndeliberate and act.  Thus, while ACIP WGs can and should examine specific topics  in detail \nand define the issues, including development of options for recommendations, the actual \nprocesses  of group deliberation terminating in development of immunization \nrecommendations must occur in the open public forum of ACIP meetings in compliance with \nFACA requirements.  \nQ.: How are “straw poll s” used during WG meetings?  \nA.: When there are several diff erent opinions about an issue expressed during a WG \nmeeting or the WG Chair and WG Lead  want to ensure all members ’ perspectives are \nconsidered, a “straw poll” can be conducted.  A straw poll is not a vote on policy  and the \ngoal is not to come to consensus,  but rather to document the different opinions of the WG \nmembers and help with continued deliberations.  Results of straw polls should be kept \nwithin the WG, but  can be summarized during a presentation at the public ACIP meeting.  \nACIP voting members, liaison representatives, and consultants with no conflicts of interest \nshould be included in straw polls. Federal employees should not be included. These polls can \nbe done over email or during teleconferences.  \nV. Confidentiality  \nUnlike ACIP meetings, which are open to the public, WG meetings/teleconferences are not \npublic meetings ; data presented during these meetings/teleconferences are often \n \n10 \n proprietary and should not b e distributed to people other than approved WG members. To  \nensure  confidentiali ty of data, the following guidelines  should be i mplemen ted by  all WGs. \n1. Roll call by  the WG Lead  should be taken at the start of each WG teleco nference  to \ndocument n ames of members who are pa rticipa ting; the roll call of participants \nshould be inco rporated into  brief meeting minutes, which  may be compiled by  the \nWG Lead  or someone de signated to do so  by her/him.  \n2. At the beginning of each  WG meeting/teleco nference where any material that is \nnot already publically available is being discussed , the WG Lead  shou ld state that \nthe meetings are closed  and i nformation  discuss ed is co nfidential and sh ould not  \nbe dis tributed or used in  presentation s. \n3. Only WG members and i nvited consul tants should  participa te in WG meetings. \n4. If the parent organization of a liaison representative wishes to obtain information \nabout WG proceedings, the organization should contact the WG Lead to request a \npresentation. Liaison representatives serving on WGs should not share WG \nproceedings, discuss ion, or slides with the parent organization unless permission is \ngranted by the person who presented this information to the WG.  \n5. Slides  distributed at WG meetings or sho wn du ring teleco nferences  should  be \nmarked as co nfidential and shou ld not be sh ared with pe ople who are  not WG \nmembers. \n6. To minimize the possibil ity that slides may be e xtracted  or used  outside the WG \nmeeting, PowerPoint  present ations should be sa ved and d istributed as .PDF \n(Portable Docume nt Format) files. \n7. WG members should not  discu ss WG deliberations with an yone representi ng or \nemployed by a vaccine manufacturer. \nVI. Pharmaceutical Companies and Work Groups  \nPresentations given by pharmaceutical companies to ACIP provide critical information on \nclinical trials and other studies assessing the safety and efficacy of vaccine products.  \nGuidance for WGs includes:  \n• If a company and or lobbyist  reaches out to a WG member  to discuss WG \nproceedings, the WG member should inform the WG lead  immediately . \n• When feasible, WGs should provide oppo rtunities for companies with plans to \nsubmit a biologics licensing  application (BLA) to FDA  for a vaccine product  to \nupdate the WG if new data are available.  Relevant updates from companies with \nproducts already licensed should be considered when new produ cts are under \nconsideration for use by the WG.  \n \n11 \n • All information, data, and slides presented during WG calls are confidential.  \nHowever, all documents related to WGs are subject to FOIA  requests.  In the event \nthat WG Lead receives a FOIA for materials from some or all WG meetings, the WG \nLead will be requested to review and provide all such materials; in consultation \nwith the CDC FOIA Office, the WG Lead may identify items that need to be \nredacted , e.g. proprietary information ( http://intranet.cdc.gov/ocio/about/foia/ ). \n• After pharmaceutical presentations to the WG and time for questions, the \ncompany should ex it the call.  The WG should discuss the implications of the data \npresented and the importance of presenting the data to ACIP  only when company \nrepresentatives have left .  \n• All presentation topics by pharmaceutical companies on the ACIP agenda must be \npresent ed to the WG prior to presentation at meetings of ACIP . \n• The final presentation for ACIP will be more concise , and should be reviewed and \napproved by the ACIP WG Chair and WG Lead (with consultation from the FDA ex \nofficio  member serving on the WG, when needed ) prior to the ACIP  meeting . \n• The WG lead (or other CDC staff member serving on the WG) should present a \nsummary of the WG’s interpretation of the data presented by the company during \nthe same ACIP session , if appropriate.  \nGuidance for pharmaceutical companies includes:  \n• Representatives of vaccine manufacturers should not contact any ACIP WG \nmember for the purpose of promoting a product scheduled for presentation at an \nACIP meeting or to suggest recommendations for consideration  by ACIP.  \n• Representatives of vaccine manufacturers should contact the WG Lead when they \nhave data they would like to present to the ACIP WG. Vaccine manufacturers also \nmay be solicited by WG Leads for  presentation on  specific topics of interest.  \n• Data that can be proposed for presentation may  include data on products under \nconsideration for licensure or post -licensure data on a product that may inform \ncurrent discussions of the WG.  \n• The time allocation for the ACIP presentation should be approximately 15 minu tes, \nwith an additional 5 minutes for questions.  Longer or shorter presentations may be \nneeded ; final time allocation s will be determined by the WG Lead and the ACIP \nsteering committee during agenda development.   \n• Presentations must be submitted to the WG Lead 3 weeks prior to the ACIP \nmeeting for review and approval.  This provides time for review and incorporation \nof feedback.  If changes are requested, the final presentation should be reviewed by \nthe WG Lead . The d eadline for final submission for printing of slides is the \nWednesday 1 week prior to the ACIP meeting.  \n \n12 \n • Any slide outlining the measures used in the studies presented should include  the \nstudy population, comparison groups, and outcome measures.  \n• A strengths and limitations slide should be included in the conclusion section of the \ntalk.  \nVII. Work Group Resources  \nThe most significant internal resources available to ACIP WGs are the expertise and energy \nof WG Leads and other CDC staff . In addition, the Secr etariat is  dedicated to support the \nwork of ACIP  WGs  including l ogistic s, oversight of issues of science and policy , day-to-day \noversight of WGs , and interactions with ACIP  membership.  \nThe ACIP Executive Secretary, or “Designated Federal Official,” (DFO) is a senior consultant \nto the Director  at the National Center for Immunization and Respiratory Diseases (NCIRD). \nThe DFO is responsible for the committee's overall management and compliance with \nFACA law.  \nAdditional resources at CDC (e.g. , the Office of General Counsel, Federal Advisory \nCommittee Management Branch/Management Analysis and Services Office) are available \nand can be accessed through the ACIP Secretariat , as well as support for GRADE and cost -\neffectiveness evaluations.  \nA monthl y meeting of WG Leads is organized by the Secretariat to get input from WG \nLeads on issues related to ACIP processes and to discuss any challenges or questions \nspecific to a WG among the WG Leads.  The Secretariat also provides support to the WG \nLeads for t he ACIP SharePoint site and coordinates annual membership agreement  and \nconflict of interest  paperwork.  \nFunds for support of ACIP activities are limited. Requests for specific support for additional \nexpenses that will enhance ACIP functioning (e.g., extra meeting rooms, equipment, travel \nof additional persons to ACIP meetings) will be considered by the ACIP Secretariat . CDC \nroutinely supports travel costs for the duration of ACIP meetings for ACIP voting members \nonly. CDC rarely may support travel for invit ed speakers making presentations during the \nACIP meeting, or may agree to provide funding for an additional night for ACIP members. \nSuch requests should be brought to the ACIP Secretariat  for consideration on a case -by-\ncase basis, with justification for th e increased costs.  In some instances, it may be necessary \nto deny reasonable requests for financial support.  \n \n13 \n VIII. Preparing for ACIP Meeting Presentations  \nSubmitting Agenda Items for ACIP Meetings  \nTopics for inclusion in the agenda for an upcoming ACIP meeting  are solicited by the ACIP \nSecretariat approximately 3 months  before the ACIP meeting, and  are due 2 weeks later. \nRequests for agenda proposals are sent to voting ACIP members, WG leads and ACIP \nSteering Committee members. A standard template form is used, and includes the \nfollowing items:  \n• Justification for inclusion of topic  \n• Proposed presentat ions, including topic, presenter, question(s) to be addressed by \nthe ACIP  \n• Any additional pertinent information  \nFollowing compilation of all agenda proposals, the ACIP Steering Committee meets to \nprepare a detailed agenda,  which is then sent back to WG L eads and any others who have \nsubmitted proposals. The ACIP secretariat finalizes the draft agenda within 1 -2 days of the \nSteering Committee meeting, and distributes and posts on the ACIP web site. The draft \nmeeting agenda may be modified as needed up to the w eek of the ACIP meeting.  \nACIP Briefing Documents  \nIn advance of each ACIP meeting, a briefing book will be prepared for the CDC Director that \nincludes information on the topics being presented at ACIP and items on which a vote will \nbe taken. The ACIP Secret ariat will request briefing documents from WG Leads after the \ndraft agenda has been distributed. Briefing documents will be due 3 weeks prior to the \nACIP meeting. A standard template form is used (not to exceed two pages), and includes \nthe following items:  \n• Topic  \n• Statement of status of the vaccine or topic and key issues  \n• Background  \n• Reason topic is being presented to ACIP: information, discussion, vote, VFC vote (if \napplicable)  \n• Policy options  \n• Consensus of ACIP WG  \n• Implications of ACIP decision  \nACIP Background Materials  \nIn order to prepare voting ACIP members, ex -officio members, and liaison representatives \nfor the issues to be discussed during each ACIP meeting, b ackground materials  are \n \n14 \n prepared and distribut ed in advance of each meeting. Background materials  can be \nsubmitted for all topics on an ACIP agenda, but are required for major issues and items  on \nwhich a vote will be taken.  Background materials will be requested from WG Leads \napproximately six weeks prior to each ACIP meeting, and will be due  two weeks in advance \nof the meeting.  \nA cover letter should be prepared that highlight s the information that is most important \nfor the members to read. Examples of cover letters may be requested from the ACIP \nSecretariat, and will be circulated when backg round materials are requested. The \nbackground materials can includ e key WG summaries, draft MMWR P olicy Notes or \nRecommendations and Reports , key articles or studies, or a summary of key issues.  \nBackground materials are not considered to be confidential an d may be shared in a limited \nfashion (e.g., by liaisons within their organizations).  If confidential information needs to be \nshared with the voting ACIP members, the WG lead should reach out to the ACIP \nSecretariat to facilitate that process.   \nACIP Prese ntations  \nWG Leads should collect meeting presentation files for meeting handouts from all presenters in \nyour session. Approximately 2 -3 weeks before each ACIP meeting the ACIP Secretariat will \nrequest presentation files for printing. The ACIP Secretariat can assist with printing needs up to \none week prior to the meeting. If there are files that should go to ACIP members only (ACIP, ex -\nofficio, liaison representatives) or voting members only, please indicate that in the file name. For \nany presentations that  are not received electronically by one week in advance of the meeting, \nthe WG Lead will be responsible for coordinating printing, photocopying, and delivery of hard \ncopy per the instructions below.  \n• Compile your presentations in sets  with handouts in chronological order;  ready to be \nslipped straight into meeting binders (e.g., if you have five individual handouts, put them in \nsets with handouts #1 , 2, 3, 4, 5 in order ). \n• For ACIP membership:  25 sets as handouts, 6 slides/page, 3 inch ho le punch, collated and \nstapled; black/ white unless you need them to be in color (e.g., child/adolescent and adult \nimmunization schedules).  \n• For public:  200 sets as handouts, six slides/ page, regular paper, collated and stapled.  \n• Delivered in labeled boxes to the Global Communications Center  (Building 19 ) marked  with \nACIP meeting, name of session and session date . \nAll presentation files will be converted to PDFs and shared with ACIP members, ex -officio, \nand liaison representatives via ShareFile prior to the meeting.  These files do not have to \nbe the final presentations and can be the same files that are used for pr inting.  Recipients \nwill be instructed that the meeting slides should not be shared or used in presentations \n \n15 \n without permission from the Work Group Lead.   Final versions of all slides presented at the \nmeeting will be posted on the ACIP website following th e meeting.  \n Electronic presentation files  will be loaded on a laptop computer in the meeting room for \npresentation at the ACIP meeting. Presentation files may be updated before the meeting \nstarts, or at breaks, on meeting days, brought to us in person on a  flash drive by the WG \nLead only . We cannot accommodate several people updating their files, all for the same \nsession.  \nWG Leads should  send the presentation files for your session to  Stephanie  Thomas \n(hkp4@cdc.gov ), as a group.  Please use the following naming format to ensure that the person \noperating the meeting computer can pull them up easily and in the proper order. For example:  \n• 01 HPV introduction Kempe  \n• 02 HPV review Markowitz  \n• 03 HPV  proposed recommendations Meites  \n• 04 HPV recommendation vote Meites  \n• 05 HPV VFC Santoli  \n• Often the manufacturers provide their files to you as PDF files; if possible,  we prefer PPT.  \nIX. Evidence -Based Decision and Cost -effectiveness Analyses  \nCDC vaccine recommendations are developed using an explicit evidence -based method \nbased on the Grading of Recommendations, Assessment, Development and Evaluation \n(GRADE) approach. Key factors considered in development of recommendations include \nthe balance of benefits  and harms, type or quality of evidence, values and preferences of \nthe people affected, and health economic analyses . More information about GRADE can be \nfound in the ACIP’s GRADE handbook \n(https://www.cdc.gov/vaccines/acip/recs/grade/downloads/handbook.pdf ).  \nMost issues that ACIP will vote upon require a GRADE evaluation of the evidence. \nHowever, a “when to GRADE” algorithm is currently un der development and once it is \nfinalized a link will be added here. A summary of the GRADE evidence should be included \nin the MMWR Policy Note, and the GRADE evidence tables are published on the ACIP \nwebsite ( https://www.cdc.gov/vaccines/acip/recs/grade/table -refs.html ). If it is \ndetermined that a GRADE evaluation is not needed, the rationale for why GRADE is not \nbeing done should be clearly documen ted. The ACIP Secretariat is available to assist with \nquestions about GRADE.  \n \n16 \n Additionally, In February 2018 the ACIP adopt ed use  of an evidence to recommendations \nframework. Information abo ut the framework will be added here and on the ACIP website \nwhen a vailable.   \nThe ACIP also provides guidance for the development of health economics studies \n(https://www.cdc.gov/vaccines/acip/committee/guidance/economic -studies.html ). These \nprocedures should be followed for economic analyses to be presented to the ACIP to \nensure that economic data presented to the ACIP and its WGs are uniform in presentation, \nunderstandable, and of the highest quali ty. \nX. Preparing MMWR Reports  \nFollowing approval by the CDC Director, ACIP ’s recommendations are published in MMWR \nas a Policy Note  whereby they become official policy . The MMWR Policy Note and \nRecommendations and Reports documents summarize both the ACIP recommendations \n(language voted upon by ACIP; e.g., the vaccine should be used for outbreak response) and \nguidance for use (CDC’s guidance for use which is not voted upo n by ACIP; e.g., how to \ndetermine when an outbreak is occurring, dose spacing, etc.).  \nDevelopment of the Policy Note is led by the WG Lead. The WG Chair and other ACIP (or \nWG) members who meet authorship criteria should be included  as co -authors on each \nPolicy Note . The Secretariat encourages WG Leads to approach ACIP members to be \nincluded as co-authors early in the process of developing the Policy Note  to allow for \nparticipation and co -authorship . The WG Lead also is responsible for developing the \nMMWR Re commendations and Reports (comprehensive summar y of ACIP \nrecommendations).  \nThe WG Lead should meet  with OADS prior  to drafting each  Policy Note  and the OADS \nChecklist should be followed  (http://intranet.cdc.gov/od/oads/osq/guide_rec/docs/CDC -\nPolicy -Notes -Development -and-Reporting -Checklist.docx ). The WG Lead should also meet \nwith MMWR prior to developi ng a Recommendations and Reports  document . \nA Policy Note should be drafted before an ACIP vote  is requested  and the draft Policy Note \nshould be distributed to ACIP members in the background materials for the session in \nwhich the vote is requested . The ACIP  Secretariat will preschedule each Policy Note with \nMMWR to ensure prompt publication  once the recommendation is approved by the CDC \nDirector.  Similarly, a Recommendations and Reports document should be drafted and \ndistributed to ACIP members before a vote  is requested.  \n \n17 \n After clearance and prior to publication, sections of the MMWR that discuss a particular \nproduct should be shared with the company making that product to ensure there are no \nfactual errors or literature that was not included. At the time whe re there are proofs, the \nembargoed document should be shared with any pharmaceutical company that has a \nvaccine named in the document (with the exception of the schedul e and general guidance \ndocuments). This is for awareness purposes only and edits can be made only if factual \nerrors are identified.  \nXI. Termination of W ork Groups  \nFive ACIP WGs are designated “permanent” WGs, since recurring tasks occur annually \n(influenza, child/adolescent immunization, adult immunization , and evidence based \nrecommendations ) or approximately every 3 -5 years (general recommendations). The \nremaining WGs are designated “task -oriented,” and are established when needed (Section \nI), and disbanded once the stated terms of reference ha ve been completed. It is often the \ncase that the WG has completed its terms of reference, but an ACIP recommendation \nstatement (P olicy Note or Recommendations & Reports for publication in MMWR) is still in \nprogress. If there is not a need to have ongoing, regular WG discussion, the WG Chair and \nWG L ead may disband the WG, and the draft recommendation s can be circulated to WG \nmembers for review and comment until a final draft is ready to put into CDC clearance.  \nIt may happen that and ACIP WG is established a nd completes its T ORs, and is then \ndisbanded but at a later date new information becomes available that necessitates \nregrouping the WG, e.g. new safety data, a new vaccine, etc. This has occurred, for \nexample, with the Rotavirus Vaccine WG. Therefore, a WG  does not need to stay in \nexistence “in case” a future need arises, but can be disbanded and reestablished as \nrequired, with the original WG members and/or with new WG members. When the WG \nChair and WG L ead agree that it is reasonable to disband the WG, th e WG Lead sends out \nan email to WG members thanking them for their service and contributions, and informing \nthem of any next steps, e.g. ACIP recommendation review and publication plans.  \n  \n \n18 \n XII. Appen dices \nAppendix 1: Additional Information for  FDA, ISO, and ISD Representatives to \nACIP WGs  \n \nFDA Representatives to ACIP Work Groups  \nIn most circumstances, the ACI P considers vaccines once they have been licensed by the \nFDA.   While ACIP reviews the safety and efficacy data available to them during \ndeliberations, they rely on FDA to conduct a review of all data submitted for \nlicensure.    Therefore, the FDA representa tive to the ACIP Work Group provides expertise \nin the licensure, indications, and package insert of vaccines under consideration.   While \ninformation being reviewed by FDA is confidential during the pre -decisional phase, the FDA \nmakes available on its websi te its reviews of the biologic license application within 30 days \nof the approval.   While the FDA representative cannot discuss trade secrets, confidential \ncommercial or financial information from the applicant, he/she can still provide guidance \nand perspe ctive to inform ACIP Work Group discussions based on publicly available \ninformation, including all information made available to the public that is not available \nelsewhere.    \n• Open lines of communication between the Work Group Lead and FDA \nrepresentative are important to ensure ACIP Work Group deliberations and \nproposed recommendations are appropriate and in line with licensure \nconsiderations and information made available to th e public by FDA upon approval \nof the vaccine.    \n• When recommendations are proposed that are not aligned with the licensed \nindications, it is important to ensure any concerns from FDA are communicated to \nthe CDC Work Group Lead.  \n• Given that the FDA represent ative is often in the middle of the review for the \nvaccine under consideration, FDA representatives are prohibited from providing \ncertain information in the ongoing review until an approval decision has been \nmade.  \n• When there are scientific or policy concer ns (i.e., differences between FDA and the \nWork Group’s interpretation of data and/or proposed recommendations) that are \nchallenging to resolve within the Work Group, both the FDA representative and the \nCDC Work Group Lead should communicate these concerns to leadership for \nfurther collaborative discussion.  \n \n19 \n Roles and Responsibilities  \n• Signs annual membership agreement.  \n• If the FDA representative has not signed an OGE 450 through FDA, they should \ncomplete the ACIP Work Group member conflict of interest form.    \n• Attends and participates in Work Group meetings on a regular basis (attends more \nthan 75% of meetings).  \n• Completes timely review of materials as requested, including pre -clearance review \nof policy notes and Recommendations and Reports.  \n• Communicates either d uring the call or follows -up with the Work Group lead if \nthere are concerns related to interpretation of data or potential conflicts between \nrecommendations and language in the package insert, as permitted under its \nregulations  \n• As able to, provides updates  to Work Group Lead about potential changes to a \nvaccine’s indications.  \n• Known or approximate distribution dates for Healthcare Provider letters indicating \nchanges to prescribing information relevant to work group deliberations should be \ncommunicated to the  CDC Work Group Lead by the FDA representatives.  \n• Respond to communications from the Work Group Lead via email or phone.   If they \nare unable to communicate a concern due to confidentiality restrictions, the FDA \nrepresentative should inform their leadershi p of potential issues.  \n \nISO Representatives to ACIP Work Groups  \nThe ISO representatives to the ACIP Work Groups plays a key role ensuring that vaccine \nsafety issues related to proposed new recommendations, changes to recommendations, \nnew vaccine safety fin dings, and potential vaccine safety issues of concern are identified \nand considered during Work Group deliberations.    \n• Vaccine safety is a key component of the review of the evidence supporting \nproposed recommendations.  \n• There may be vaccine safety issues f or special populations that may not be \nrecognized by the ACIP Work Group, such as vaccination of pregnant women, or \nimmunocompromised populations.  \n• There may be vaccine safety findings from routine surveillance, epidemiologic \nstudies, or new issues of conce rn from provider groups, health officials or the \ngeneral public for which the ACIP Work Group should be made aware.  \n \n20 \n • When recommendations are proposed for which there are potential vaccine safety \nconcerns, it is important that these concerns are communicat ed to the CDC Work \nGroup Lead.  \n• When there are vaccine safety or policy concerns (i.e., differences between ISO and \nthe Work Group’s interpretation of data and/or proposed recommendations) that \nare challenging to resolve within the Work Group, both the ISO representative and \nthe CDC Work Group Lead should communicate these concerns to their leadership \nfor further collaborative discussion.    \nRoles and Responsibilities  \n• Signs annual membership agreement.  \n• If the ISO representative has not signed an OGE 450 through CDC, they should \ncomplete the ACIP Work Group member conflict of interest form.    \n• Attends and participates in Work Group meetings on a regular basis (attends more \nthan 75% of meetings).  \n• When neede d, the ISO representative should pull available data, review literature, \nand conduct analyses to support ACIP Work Group deliberations.  \n• Completes timely review of materials as requested, focusing on vaccine safety and \nthe safety studies supporting licensur e.  The ISO representative may be requested \nto co -author policy notes or recommendations and reports depending on the \ncontent.  \n• Communicates either during the call or follows -up with the Work Group Lead if \nthere are concerns related to implementation issues . \n• Presents related vaccine safety updates at ACIP meetings, as needed.  \n \nISD Representatives to ACIP Work Groups  \nThe ISD representative to the ACIP Work Groups plays a key role ensuring that \nimplementation issues related to proposed new recommendations or changes to \nrecommendations are identified and considered during Work Group deliberations.    \n• Implementations issue s are considered as one piece of the evidence supporting \nproposed recommendations.  \n• While the scientific evidence should drive ACIP recommendations, implementation \nissues can help refine potential policy options supported by the evidence.  \n• Understanding impl ementation issues can also help how recommendations are \nframed.  \n \n21 \n • Clinical decision support is a key part of implementation of vaccine \nrecommendations.   Projecting how recommendations are translated into clinical \ndecision support can also help refine potenti al policy options and clinical guidance.  \n• When recommendations are proposed for which there are implementation \nconcerns, it is important that these concerns are communicated to the CDC Work \nGroup Lead.  \n• When there are implementation or policy concerns (i.e.,  differences between ISD \nand the Work Group’s interpretation of data and/or proposed recommendations) \nthat are challenging to resolve within the Work Group, both the ISD representative \nand the CDC Work Group Lead should communicate these concerns to their \nleadership for further collaborative discussion.    \nRoles and Responsibilities  \n• Signs annual membership agreement.  \n• If the ISD representative has not signed an OGE 450 through CDC, they should \ncomplete the ACIP Work Group member conflict of interest form.    \n• Attends and participates in Work Group meetings on a regular basis (attends more \nthan 75% of meetings).  \n• When needed, the ISD representative should pull available data, review literature, \nand conduct analyses around implementation issues to support ACIP Work  Group \ndeliberations.  \n• Completes timely review of materials as requested, focusing on implementation \nissues including language, how recommendations will be communicated, and how \nthey will be incorporated into clinical decision support.  \nCommunicates either d uring the call or follows -up with the Work Group Lead if \nthere are concerns related to implementation issues.", "summary": "ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES :  WORK GROUPS   Standard Operating Procedures: August 201 8                                      Advisory Committee on Immunization Practices Secretariat   Centers for Disease Control and Prevention     2     Contents   I. Overview of Advisory Committee on Immunization Practices Work Groups  ..... 2  II. Work Group Membership  ................................ ................................ ........................  4  III. Roles and…", "source_url": "https://www.cdc.gov/acip/our-work/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/Work-Group-Guidance-508.pdf", "case": "acip", "sub_case": "other", "tags": ["acip", "cdc", "vaccines", "other"], "page_count": 21}
{"title": "ACIP conflicts interest policy", "content": "ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES: \nWORK GROUPS  \nConflict of Interest Policy : December 2023  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \nAdvisory Committee on Immunization Practices Secretariat  \nCenters for Disease Control and Prevention  \n2 \n ACIP W ork Group s (WG)  serve a key scientific role in support of vaccine policy development by \nACIP. In order to avoid undue influence or the appearance /perception  of a conflict of interest in \nWG discussions, screening for potential conflicts  will be conducted  upon establi shment of a WG \nand annual updates  will be collected  from WG members to ensure that financial or other conflicts \nare not present and/or have not changed.  The ACIP Secretariat will assist with the collection of \nconflict of interest disclosures ; screening of the conflict of interest declarations  will be conducted \nby the WG Lead in conjunction with the ACIP Secretariat.   \nThe ACIP Secretariat will consider issuance of waivers to this conflict of interest policy in limited \nsituations.  Waivers may be issued  if it is determined that an individual’s subject matter expertise \nis necessary for work group deliberations and another expert is not available who could fulfill this \nrole.  In situations where a waiver is granted, the conflict of interest (or perceived conflic t of \ninterest) should be regularly announced to the WG.  \nNote: The conflict of interest policy for ACIP WG members outlined here applies to vaccines or \nrelated products under the purview of each ACIP WG on which a person serves, as well as the \npharmaceutica l company(s) that manufactures  the vaccines or related products under the \npurview of each ACIP WG on which a person serves.   \nBecause WG members  are most familiar with their own situations, their personal responsibilities \ninclude the following: (1) to alert the WG Lead about any possible conflict of interest that may \nimpact perception of impartial and fair activities of WG members and (2) to ident ify and certify on \nan annual conflict of interest screening form  (a) any aspect of the work of the ACIP WG where a \nconflict of interest exists, and (b) that there will not be, and has not been, involvement in the \nefforts of the WG where participation const itutes a conflict of interest.  \nWhen a possible conflict of interest is reported by a WG member, t he WG Lead will consult with \nthe ACIP Executive Secretary (and legal counsel if necessary), to determine whether the  particular \nsituation involves a conflict of interest or an appearance /perception  of a conflict of interest which  \n1) requires that the WG member  not be involved in the ACIP WG process , or 2) the potential \nconflict of interest must be disclosed to the WG, but participation in the ACIP WG process is  \nallowed .  \nA conflict of interest exists when a participant has a  financial  interest in a vaccine product , related \nproduct (e.g., monoclonal antibody),  or pharmaceutical company that manufactures vaccines (or \nrelated products ) that may affect his/her imput ed financial interests or potentially bias his/her \napproach to development of options for recommendations for use of that vaccine, or of a \ncompeting vaccine.   \nIn addition, WG member s who feel they might be unable to provide impartial advice on the matter \nat issue for any reason, or who have made public statements (written or oral) that would indicate \n3 \n to an observer that you have taken a position on the products or issue under consideration should \ndisclose this as a potential conflict of interest . \nRegardless  of the level of financial involvement or other conflict of interest, if the participant feels \nunable to provide objective advice, they  must recuse themsel f from the WG activities under \nconsideration. The ACIP WG process relies on the integrity of each par ticipant to disclose to the \nWG Chair or WG Lead any real or apparent conflicts of interest that are likely to bias the \nreviewer’s evaluation of an application or proposal.  \nThe following guidance and definitions will assist in determining whether a conflic t of interest \nexists.  This guidance applies to vaccines or related products under the purview of each ACIP WG \non which a person serves and the pharmaceutical company(s) that manufactures  the vaccines or \nrelated products under the purview of each ACIP WG on which a person serves .  This guidance is \nnot all -inclusive, due to the variety of possible conflicts of interest and the potential for \nappearance of conflicts of interest.  \nSituations where a conflict of interest exists and the individual should not serve as a WG \nmember includ e: \n1. A person or a member of their immediate family is employed directly by a vaccine /product  \nmanufacturer or its parent company. A member of the immediate family includes spouse , \ndomestic partner , or child . \n2. A person or a member of their immediate family hol ds stock in a vaccine/product \nmanufacturer or its parent company in excess of the OGE de minimus amounts \n(https://ethics.od.nih.gov/waiver ).   \n3. A person  is a holder of, or otherwise is entitled to royalties or other compensation for, a \npatent (planned, issued, or pending) on a vaccine/product or process, immunologic agent, \nadjuvant, or preservative that can be used for a vaccine that may come before ACIP for \nreview/discussion during the anticipated term of the concerned WG.  \n4. A person holds a paid advisory or  consulting role  with a manufacturer  to perform work \nrelated to vaccines /products  expected to be considered by the WG or companies that \nmanufacture vaccines/p roducts under the purview of the WG . A person must agree  to \nforego such paid consultation or membership during his/her tenure on the ACIP WG  \n(except participation in research studies  or service on data monitoring boards  – see \nbelow ). \n5. A person is a 1) princ ipal investigator, 2) co-principal investigator, or 3) a site principal \ninvestigator for an industry sponsored clinical trial involving a vaccine  or manufacturer  \nunder the purview of the WG  (even when funding goes to the institution/program).  \n6. WG members should agree that they  will not serve as a paid litigation consultant or expert \nwitness in litigation involving a vaccine  or manufacturer  under the purview of the WG . \n4 \n Potential conflicts of interest  that  should be disclosed but do not limit1 part icipation of the \nindividual on the WG include:   \n1. WG members are required to disclose participation in  conducting  research studies funded \nby pharmaceutical companies  and service on data monitoring boards  (paid or unpaid) . \n2. WG members  should disclose any uncompensated single time participation in advisory \nboards, or lectures on behalf of a pharmaceutical company that occurred in the prior 6 \nmonths .  Participation in these activities should cease during tenure on the WG.   \n3. WG members sh ould disclose any honoraria  received  for continuing medical education \n(CME) presentations that occurred i n the prior 6 months where the source of funding was \nan unrestricted grant to the CME provider by a vaccine manufacturer and where all CME \nrules and  regulations are followed.   Participation in these activities should cease during \ntenure on the WG.   \n4. Non-financial conflicts  (e.g. uncompensated participation in vaccine development, or a \nresearcher identified with  a particular scientific perspective in a controversial area),  should \nalso be disclosed and considered prior to participation.  \n5. WG members should disclose any potential reaso ns th ey might be unable to provide \nimpartial advi ce, or any reason that their impartiality in the matter might be questioned.  \nIn addition, public statements (written or oral) that would indicate to an observer that the \nWG member has taken a position on th e products or issue under consideration should be \ndisclosed.  \nActivities not considered a potential conflict of interest include:  \n1. WG members may  receive travel reimbursement for continuing medical education (CME) \npresentations where the source of funding is  an unrestricted grant to the CME provider by \na vaccine manufacturer and where all CME rules and regulations are followed.  \n2. Discussions with pharmaceutical representatives in regards to purchasing vaccines for a \nclinical practice.  \nWG members have an ongoing  obligation to bring any new information regarding potential \nconflict(s) of interest to the attention of the  WG Lead. In addition, WG members must inform the \nWG Lead if they are contacted directly by a representative of a vaccine manufacturer regarding a \nvaccine /product  under consideration by the WG on which they serve; the WG Lead will then \ninform the ACIP Secretariat of any such contact.  \n \n \n1 Waivers may be issued by the Secretariat  in consultation with the work group lead.", "summary": "ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES:  WORK GROUPS   Conflict of Interest Policy : December 2023                                       Advisory Committee on Immunization Practices Secretariat   Centers for Disease Control and Prevention   2   ACIP W ork Group s (WG)  serve a key scientific role in support of vaccine policy development by  ACIP. In order to avoid undue influence or the appearance /perception  of a conflict of interest in  WG discussions, screening for potential…", "source_url": "https://www.cdc.gov/acip/our-work/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/ACIP-conflicts-interest-policy.pdf", "case": "acip", "sub_case": "other", "tags": ["acip", "cdc", "vaccines", "other"], "page_count": 4}
{"title": "child schedule tor 508", "content": "Page 1 of 7 \n Advisory Committee on Immunization Practices  (ACIP) , \nCenters for Disease Control and Prevention (CDC)  \nChildhood and Adolescent  Immunization Schedule Workgroup  \nTerms of R eference  \nUPDATED: October 8 , 2025  \n \n \nPUR\nPOSE  \n \nThi\ns document defines the activities, membership, and administrative requirements \nassociated with the establishment of a C hildhood and Adolescent Immunization \nSchedule  Workgroup under the Advisory Committee on Immunization Practices  \n(ACIP) , Centers for Disease Control and Prevention (CDC).  ACIP utilizes subgroups of \nthe Committee, known as Workgroups (WGs), to review relevant published and unpublished data, and clinical and scientific knowledge,  and develop options for \npresentation to the full ACIP  parent committee  during its public meetings to facilitate \ndiscussion, deliberation and development of recommendations  to the CDC Director .  \nACIP WGs are intended to augment the effectiveness of ACIP. The direction, focus, and pace of both ACIP and  the individual WGs are guided by CDC and HHS policies and \npriorities, and by the  need for expert input to inform development of  CDC immunization \npolicy. ACIP WGs are task oriented and convene in response to specific policy needs. \nWGs  serve a key role in providing expertise for the use of  immunizations in support of \nthe full committee  deliberations and recommendations. Each WG operates under \nspecific terms of reference and disbands  when current WG  activities are completed. \nThe Childhood and Adolescent  Immunization Schedule WG has been specifically \nestablished to review data, as well as clinical and scientific knowledge related to the \nchildhood and adolescent  immunization schedule to help develop childhood and \nadolescent  immunization schedule policy options  for ACIP consideration to formulate \nrecommendations to the Director of the CDC.   \n \nFor\n the purposes of this document, i mmunization refers to vaccines and other antibody \nprotective products , to prevent disease, e.g., immunoglobulins .  \n  \nBACKGRO\nUND  \n \nWhi\nle many vaccines are universally recommended worldwide, different countries have \ndifferent vaccine schedules  for a variety of rea sons , both in terms of the collection of \nvaccines given and the timing and order of the vaccines.  These reasons can include  \nimplementation considerations ( differen ces in  healthcare systems , and variance in \npractices related to pediatric medicine practice) and concerns about vaccine safety and \nadverse events .  As part of ACIP ’s core mission  to develop recommendations on the \nuse of vaccines in the civilian population of the United States, the  committee is standing \nup a WG  focused on assessing  the safety  and effectiveness  of the childhood and \nadolescent  schedule. The rationale for this WG  includes considerations such as  the use \nof new  vaccine technologies and ingredients , and the rise of vaccine hesitancy . These \nPage 2 of 7 \n activities  should not only be based on past research but also future vaccine studies . If \nsuch studies reveal unexpected but scientifically  validated concerns, the schedule \nshould be adjusted  accordingly .    \n \nIn 2\n002, the Institute of Medicine (IOM), now the National Academy of Medicine , \npublished Immunization Safety Review: Multiple Immunizations and Immune \nDysfunction1 and noted that :  \n \n“\nThe committee was unable to address the concern of some that repeated \nexposure of a susceptible or fragile child to multiple vaccines over the \ndevelopmental period may also produce atypical or nonspecific immune or nervous system injury that could lead to severe disability or death...There are no \nepidemiological studies that address this, either in terms of exposure or outcome. That is, there is no study that compares an unvaccinated control group with children exposed to the complete immunization schedule, or are there any studies that looked at health outcomes other than those classically defined, such as infections, allergy, or diabetes. Thus the committee recognizes with some discomfort that this report addresses only part of the overall set of concerns  of \nsome who are most wary about the safety of childhood vaccines. ” (page 36)   \n \nT\nhe report also noted that one- quarter of parents expressed concern about the number \nof immunizations children were receiving and concluded that,  \n“Concern about multiple immunizations has been, and could continue to be, of \nsocietal significance in terms of parental worries, potential health burdens, and future challenges for immunization policy making.” (pages 104- 105) \n \nO\nver a  decade later, in 2013, the IOM published The Childhood Immunization Schedule \nand Safety: Stakeholder Concerns, Scientific Evidence, and Future Studies ,2 the report \nof an expert committee that had been tasked with reviewing “scientific findings and stakeholder concerns related to the safety of the recommended childhood immunization schedule,” and identifying “ potential research approaches, methodologies, and study \ndesigns that could inform this question, including an assessment of the potential strengths and limitations of each approach, methodology and design, as well as the financial and ethical feasibility of doing them. ” (page 3) The committee noted: \n \n “\nFew studies have comprehensively assessed the association between the \nentire immunization schedule or variations in the overall schedule and categories of health outcomes, and no study has directly.”...“Studies designed to examine the long- term effects of  the cumulative number of vaccines or other aspects of \nthe immunization schedule have not been conducted. Nevertheless, and its literature review, the committee found useful designs for studies to measure exposures and outcomes and identified strategies f or expanding or adapting \nconventional study designs to clearly address whether any adverse health outcomes are associated with the overall immunization schedule.” (page 5- 6) \n \nPage 3 of 7 \n To assess the feasibility of studying the vaccine schedule, the IOM solicited a report \nfrom Dr. Martin Kulldorff , a biostatistician and epidemiologist  at Harvard Medical School . \nHe concluded that “ a wide variety of different vaccine schedule components can be \nstudied”, including “ the timing of individual vaccines, the timing between doses of the \nsame vaccine, the interaction effect between vaccines and concurrent health conditions or pharmaceutical medications, the interaction effects of different vaccines given on the same day, the ordering of different vaccines, and the effect of cumulative summary metrics such as the total number of vaccines or the total amount of some vaccine ingredient ”. He also outlined possible “study designs for the comparative evaluation of \none or more complete schedules” , considering methods “both for adverse events with \nan early onset, which are the easiest to study, and for adverse events with a late onset, including serious chronic conditions” . \n \nA r\necommendation of the  IOM committee was: \n \n“that\n the Department of Health and Human Services incorporate study of the \nsafety of the overall childhood immunization schedule into its processes for setting priorities for research, recognizing stakeholder concerns, and establishing the priorities on the  basis of epidemiological evidence, biological plausibility, and \nfeasibility.”  (page 132)  \n \nIn ac\ncordance with the ACIP Charter, t he Childhood and Adolescent Immunization \nSchedule WG and its members  will prepare information for the ACIP members to \nenable them to  make recommendations that consider :  \n \n• T\nhe timing and order of different vaccines.  \n• The concurrent administration of various vaccines.  \n• The safety of ingredients that are present in multiple different vaccines.  \n• The efficacy and safety of different vaccine schedules used in different countries.  \n• Implementation considerations , including burden on healthcare  and payor  \nsystems, economic impact, and acceptability and feasibility with input from pediatric healthcare providers and parents . \n \nTh\ne WG will also consider these issues for particular subgroups  of children, such as \nchildren born pre- maturely, children with immune deficiencies, or children with cancer .  \n \nTh\ne WG will engage external subject matter experts, as needed, to support \nimplementation of key activities.  \n \nTOPICS UNDER DISCUSSION BY THE WORKGROUP  \n \nIn accordance with the ACIP Charter and in a multi- year effort, the Childhood and Adolescent \nImmunization Schedule WG  members  will work with expert consultants as appropriate and in \naccordance with FACA statutory requirements and policies, to prepare information for the ACIP \nmembers to enable them to make recommendations on:  \nPage 4 of 7 \n • The timing and order of different vaccines.  For example, should the last toddler \ndose of the non- live DTaP vaccine be given before, on the same day , or after the \nMMR vaccine?  \n• The concurrent administration of various vaccines  and other immunizing products  \nsuch as monoclonal antibodies . For example, does the risk of post -vaccination \nfebrile seizures increase or decrease  with concom itant administration?  \n• The safety of ingredients that are present in multiple different vaccines.  For \nexample, do either of the two different aluminum adjuvants increase the risk of \nasthma?  \n• The efficacy and safety of different vaccine schedules used in different countries.  \nFor example, are there differences in efficacy or safety between the U .S. and \nDanish childhood vaccine schedules?  \n \n \nDES\nCRIPTION OF  WORKGROUP  ACTIVITIES   \nThe following activities provide a framework for the Childhood and Adolescent \nImmunization Schedule WG  multi -year efforts , which may involve data requests  from \nother Federal and non-Federal  entities : Review and summarize existing knowledge from \npublished and unpublished research and safety surveillance systems . This work may \ninclude the following three multi -faceted tasks , which may be completed in sequence or \nin parallel : \n• Identify gaps in and collaborate accordingly to address new research studies  that \nascertain important aspects of the vaccine schedule, particularly  from CDC’s \nVaccine Safety Datalink (VSD), from F ood and D rug Administration’s Biologics \nEfficacy and Safety System (BEST), and the National Institute s of Health through \ntheir extramural grant awards program.  \n• Based on the highest quality studies, determine whether a change in the vaccine \nschedule may be warranted, outline various options, and vote on which option to recommend to the full ACIP for consideration . \n• Communicate the deliberations and recommendations to the full ACIP, for them to review and vote on. Together with the WG majority views, minority views will \nalso be communicated to the full ACIP, with rationales for the different opinions.  \n \n \nMEMBERSHIP  \n \nWork group Leadership:  The Childhood and Adolescent Immunization Schedule WG  is \nchaired by one of the ACIP  members appointed to serve as  a Special Government \nEmployee.  The Workgroup Lead (WGL ) is a WG designated federal employee (DFO), \nidentified  by the Immediate Office of the Director  (IOD)  in consultation with the \nappropriate CDC program . The WG Chair , in consultation with the WGL, ACIP  DFO , \nPage 5 of 7 \n and CDC IOD, determines the WG ’s membership and work priorities  and deliverables  to \nthe full ACIP committee .   \n \nWorkgroup Membership:  The Childhood and Adolescent Immunization Schedule WG  is \ncompo sed of  experts from a variety of disciplines who are appointed based on their \nprofessional, scientific, technical, or other expertise . The y are experts who are  regarded \nas an authority or a practitioner of unique competence and skill by other persons in their  \nprofession, or occupation. Upon request, HHS federal agencies name d in the ACIP \ncharter may  also appoint members to serve on WG s. The WG will engage with the \nfollowing disciplines on WG activities : \n \n• Public health science and practice;  \n• Public health policy development, analysis, and implementation, including \ndevelopment and execution of immunization programs for children and adolescents ; \n• Clinical and medical practice, and patient- care experience ;  \n• Epidemiology;  \n• Biostatistics  \n• Molecular biology;  \n• Immunology;  \n• Virology;  \n• Toxicology  \n• Drug  and vaccine  safety; and  \n• C onsumer perspectives and/or social and community aspects of immunization \nprograms  \n \nDue to the complexity and variability of information to be gathered, additional external \nsubject matter experts may also be invited to provide data and presentations  to the WG \nand answer questions during Childhood and Adolescent Immunization Schedule WG  \nmeetings on an ad hoc basis. Such additional external subject matter experts will not be \nmembers of the WG and will not participate in any deliberations or WG discussions. \n \n \nMEETINGS, ADMINISTRATION, and TIMELINES  \n \n1. Administrative Oversight : The WGL  will work with the WG Chair to arrange meetings, \ndocument meeting proceedings, and report to the ACIP on the Childhood and \nAdolescent Immunization Schedule WG ’s activities and  findings.   \n \n2. Meet\ning frequency  and location: The Childhood and Adolescent Immunization Schedule \nWG will meet  on an as needed basis as determined by the WG Chair and WGL . All \nChildhood and Adolescent Immunization Schedule WG  meetings are convened virtual ly \nvia teleconference.  \n \n3. Meet\ning structure : In addition to the WGL,  at least two ACIP Special Government \nEmployee member s (one of whom serves as  the Childhood and Adolescent \nPage 6 of 7 \n Immunization Schedule WG  Chair ) must be present at each meeting for a quorum .  An \nagenda, relevant publications, and background documents will be circulated as read-\nahead mat erial before each meeting.  \n \n4. C\nonflicts of Interest : WG members will complete an ACIP WG Agreement and Conflict \nof Interest Certification  process  prior to participation on the WG. The WGL or designee \nwill screen for conflict of interest declarations and share any conflicts with the ACIP \nDFO . The ACIP DFO in collaboration with the WGL will work with the CDC Ethics  and \nIntegrity  Office within the Office of Strategic Business Initiatives (OSBI) and the Office of \nGeneral Counsel (OGC), as needed, to resolve any conflicts . WG members  will consent \nto abide by several guiding principles and disclose interests (e.g.,  employment, special \ninterests, grants, or contracts) that a reasonable person could view as conflicts or potential conflicts of interest with their Childhood and Adolescent Immunization Schedule WG participation. Members will also disclose any potential conflicts of interest before each meeting. If a Childhood and Adolescent Immunization Schedule WG \nmember indicates a potential or actual conflict of interest t o the WGL , the WGL or a \ndelegate will review and bring up any conflicts to the ACIP DFO  to determi ne whether \nthe individual must  recuse themselves from participating  in WG discussions that \nimplicate such a conflict -of-interest concern. If needed, the ACIP DFO will engage OSBI \nand OGC to assist with making COI determination.  \n \n5. Co\nnfidentiality : The discussions of the Childhood and Adolescent Immunization \nSchedule WG may include information that is unpublished, protected, privileged, or confidential . WG deliberations, including, as appropriate,  policy options  under \nconsideration by the WG , are also considered confidential . Information of this nature \nmust not be disseminated, distributed, or copied to persons not authorized to receive such information.  When these types of information are distributed, the person/s \npresenting will identify the information as such, so all members are duly informed; and written materials shall be clearly marked as such.  Unlike ACIP meetings, which are \nopen to the public, Childhood and Adolescent Immunization Schedule WG teleconferences are not subject to the open meeting requirements  of the Federal \nAdvisory Committee Act or the GSA Final Rule; data presented during these \nmeetings/teleconferences are often proprietary and should not be distributed to people \nother than approved Childhood and Adolescent Immunization Schedule WG members.   \n \n6. CDC S\ntaff Involvement : CDC staff do not serve as members of the Childhood and \nAdolescent Immunization Schedule WG but may provide administrative support and technical expertise to ACIP WGs, bringing subject matter expertise and current professional focus in areas relevant to the goal s of the Childhood and Adolescent \nImmunization Schedule WG . Consultation or information al presentations by CDC staff \nwill be transparent and evident to minimize the risk of, or the appearance of, undue influence that would compromise the independence of the WG . The ACIP , CDC DFO \nand WGL of Childhood and Adolescent Immunization Schedule WG, in consultation with \nthe WG Chair of the Childhood and Adolescent Immunization Schedule WG , will \nmonitor the interaction between the WG and the agency  staff to ensure that the WG \nPage 7 of 7 \n activities and work products are appropriate and that there is not undue influence by the \nCDC or by any special interest group on the activities  or work products  of the WG.  \n \n7. Time\nlines: ACIP WGs are established when needed and terminated once the activities \nand work products stated in the terms of reference have been completed  and the WG’s \ncharge has been fulfilled.  \n \n8. Work\ngroup Meeting Summaries:  Meeting minutes will be created by the WGL or WGL’s \ndelegate to capture the information gathered during each Childhood and Adolescent \nImmunization Schedule WG  meeting and teleconference.   \n \n9. Work\ngroup findings : The Childhood and Adolescent Immunization Schedule WG  will \npresent findings (briefing documents, background materials, presentations) to ACIP for consideration and deliberation in a public meeting.  Final versions of all slides presented at the ACIP meeting will be posted on the ACIP website following the meeting and included in the committee’s official records.   \n \n10. Work\ngroup Record Keeping : All CDC FACA committees, subcommittees, and WGs are \nsubject to the Federal Records Act. All records will be uploaded in the Federal Advisory Committee Management Portal. The summary report and other WG documents will become part of the ACIP’s official records as required by GENERAL RECORDS SCHEDULE 6.2: Federal Advisory Committee Records. WGL or the WGL’s delegate is \nresponsible for ensuring WG record keeping.   \n \nRECORDKEEPING and REPORTING  \n \nThe WG Chair and /or WGL will present  findings  / outcomes  / observations  / \nrecommendations  to the ACIP  parent committee for discussion, d eliberations, further \ndevelopment of recommendations  and vote in an open public forum . Approved ACIP \nrecommendations adopted by the CDC Director will be published in the Morbidity and \nMortality Weekly Report (MMWR ). In addition, approved ACIP recommendations will be \nincluded in the ACIP meeting minutes  and annual report.   \n \n \nREFERENCES  \n \n1. Immunization Safety Review: Multiple Immunizations and Immune Dysfunction. \nNational Academies Press; 2002. doi:10.17226/10306  \n2. The Childhood Immunization Schedule and Safety: Stakeholder Concerns, Scientific \nEvidence, and Future Studies . National Academies Press; 2013. doi:10.17226/13563", "summary": "Page 1 of 7   Advisory Committee on Immunization Practices  (ACIP) ,  Centers for Disease Control and Prevention (CDC)   Childhood and Adolescent  Immunization Schedule Workgroup   Terms of R eference   UPDATED: October 8 , 2025       PUR POSE     Thi s document defines the activities, membership, and administrative requirements  associated with the establishment of a C hildhood and Adolescent Immunization  Schedule  Workgroup under the Advisory Committee on Immunization Practices   (ACIP) ,…", "source_url": "https://www.cdc.gov/acip/our-work/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/child-schedule-tor-508.pdf", "case": "acip", "sub_case": "other", "tags": ["acip", "cdc", "vaccines", "other"], "page_count": 7}
{"title": "COVID19 TOR 508", "content": "Page 1 of 6 \n  \nAd\nvisory Committee on Immunization Practices , \nCenters for Disease Control and Prevention (ACIP, CDC)  \nCOVID-19 Immunization Workgroup   \nTerms of R eference  \nUPDATED:  August 20, 2025 \n \nP\nURPOSE  \n \nT\nhis document defines the activities, membership, and administrative requirements associated \nwith the establishment of a COVID-19 Immunization Workgroup  under the Advisory \nCommittee on Immunization Practices, Centers for Disease Control and Prevention (ACIP, \nCDC).   ACIP utilizes subgroups of the Committee, known as Workgroups (WGs), to review \nrelevant published and unpublished data , and clinical and scientific knowledge,  and develop \noptions for presentation to the full ACIP  parent committee  during its public meetings to facilitate \ndiscussion, deliberation and development of recommendations.  ACIP WGs are intended to augment the effectiveness of ACIP.  The direction, focus, and pace of both ACIP and the individual WGs are guided by CDC and HH S policies and priorities, and by the need for expert \ninput to inform development of CDC  immunization policy. ACIP WGs serve a key scientific \nrole in support of immunization  recommendations.  The COVID -19 Immunization  WG has been \nspecifically established  to review data, as well as clinical and scientific knowledge on COVID -\n19 immunization s, to help develop COVID -19 immunization  policy options for ACIP \nconsideratio n to formulate recommendations to the Director of the CDC.  \n \nF\nor the purposes of this document, Immunization refers to vaccines and other antibody protective \nproducts, to prevent disease, e.g., immunoglobulins.  \n \nB\nACKGROUND \n \nC\nOVID-19 is a disease caused by the SARS-CoV-2 virus. F or some patients, COVID -19 can  be \nsevere, causing significant morbidity and mortality. Currently there are three vaccine manufacturers (Moderna, Novavax, and Pfizer) with a combined four COVID -19 vaccines \nauthorized or approved for use in the United States. As the SARS-CoV-2 virus evolves, new formulations of the COVID-19 vaccine have been developed to better approximate currently \ncirculating strains.  \n \nT\nhe COVID -19 WG was established in 2020 and met frequently to discuss immunization  \nrecommendations as the COVID -19 pandemic evolved. ACIP  has three scheduled meetings per \nyear, and as needed, to provide recommendations on existing and/or newly developed vaccines .   \n \nA\nccording to the 21st Century Cures Act (PL 114-255), ACIP shall also , as appropriate, consider \nnew vaccines or new indications at its next regularly scheduled meeting after licensure; if the Committee defers making a recommendation, it will provide an update on the status of its review. Ad ditionally, ACIP shall make recommendations in a timely ma nner for vaccines  that \nare designated as breakthrough  interventions or could be used in a public health emergency. \n \nPage 2 of 6 \n The purpose of this WG is to review available data, as well as clinical and scientific knowledge, \nto support the development of recommendations for ACIP consideration that are used to advise the Director of the CDC.  \n \nIn\n accordance with the ACIP Charter, the COVID -19 WG will prepare information  for the ACIP \nmembers to enable them to:  \n• Advise on population groups and/or circumstances in which a vaccine or related agent is recommended.  \n• Provide recommendations on contraindications and precautions for use of the vaccine and related agents and provide information on recognized adverse events.  \n• Provide recommendations that address the general use of vaccines and immune globulin \npreparations as a class of biologic agents, use of specific antibody products for prevention of infectious diseases, and special situations or populations that may warrant modifi cation \nof the routine recommendations. \n• Support committee deliberations on use of immunization  to control disease including \nconsideration of disease epidemiology and burden of disease, immunization  safety, \nimmunization  efficacy and effectiveness, the quality of evidence reviewed, economic \nanalyses, and implementation issues.  \n• Revise or withdraw their recommendation(s) regarding a particular immunization  as new \ninformation on disease epidemiology, immunization  effectiveness or safety, economic \nconsiderations, or other data that becomes available.  \n \nT\nhe WG will also assist and support A CIP, i n accordance with Section 1928 of the Social \nSecurity Act, to be able to establish and periodically review and, as appropriate, revise the list of immunization  for administration to children and adolescents eligible to receive immunizations  \nthrough the Vaccines for Children Program, along with schedules regarding the appropriate dose and dosing interval, and contraindications to administration of the pediatric immunization .  \n  \nTOPICS UNDER DISCUSSION BY THE WORKGROUP  \n \nThe following topics relevant to  COVID- 19 immunization  for effective control of COVID -19 \ndisease in the civilian population of the United States  will be under discussion in the WG in \nmulti- year effort s.   \n1) Risk-benefit and cost-benefit analyses of existing and newly FDA-authorized mRNA and \nother COVID -19 immunizations , and immunization  schedules as it relates to COVID -19 \nimmunization  to inform use recommendations, personalized per age-group, major risk factors \nand health status.  \n \n2) T\no identify critical gaps in the existing scientific  and clinical  knowledge and methodologies \nrelated to the safety and efficacy of the COVID -19 immunizations , to inform the \ndevelopment of policy recommendations and further analyses and research by the CDC, \nother related federal agencies , and the scientific community.  \n \nPage 3 of 6 \n 3) To review and summarize data, clinical and scientific knowledge related to adverse events  \nassociated with COVID -19 immunizations  to inform immunization recommendations in \nterms of precautions and contraindications to receipt of immunization .  \n \nDE\nSCRI PTION of WORKGROUP  ACTIVITIES   \nThe following activities provide a framework for the COVID-19 immunization WG multi- year \nefforts which may involve data requests from other Federal and private partners:    \n1. Review  and summarize existing  data and published and unpublished research and clinical \nknowledge related to the safety, effectiveness, and immunogenicity of COVID -19 \nimmunizations  authorized  or approved in the United S tates. \n2. Summarize literature r eview s of the epidemiology of COVID-19 disease and SARS -CoV-2 \nvirus. \n3. Assess the benefit -risk balance for administration  of COVID -19 immunization products at \nthe same time as other immunization s. \n4. Identify areas where additional data and research  are needed to inform COVID-19 \nimmunization  recommendations.  \n5. Develop COVID-19 immunization  recommendations . \n6. R eview and  summarize the existing clinical and scientific information available ; and gaps in \nthe existing knowledge, including from other federal agencies like the FDA , where \nappropriate relating to bio distribution, pharmacokinetics and persistence of the spike protein, \nmRNA, and lipid nanoparticles to inform immunization recommendations .  \n7. Review and s ummarize the existing clinical and scientific information (including from \nfederal agencies like the FDA , where appropriate); gaps in the existing knowledge regarding \npotential impurities  (e.g., DNA contamination and endotoxins) in existing  immunization  \nproducts and the ir health impacts to inform immunization recommendations.  \n8. Review and summarize the existing scientific knowledge, and gaps, regarding the cumulative \nshort- and long-term impact of repeated boosting immunization  including non- specific \neffects (e.g., IgG4 class switching, immune imprinting, viral evolution under leaky immunizations ) to help inform immunization recommendations. \n9. Examin e the impact of COVID -19 immunization  on COVID-19 and all cause deaths, \nhospitalizations , and disability  to inform immunization recommendations. \n10. Analyze existing data and scientific knowledge regarding cardiovascular, thrombotic, neurological, immunological and othe r serious adverse events potentially caused by COVID-\n19 immunization .  \n11. Review and s ummarize available data, information , and gaps regarding long-term Covid \neffects from scientific literature  and clinical experience associated with COVID -19 \nimmunization products and COVID-19 infection to inform policy recommendations.   \n12. Map existing COVID-19 immunization  policies in countries around the world and how they \ncompared to the US. \nPage 4 of 6 \n 13. Analyze existing data and scientific knowledge related to the safety of COVID -19 \nimmunization  during pregnancy. \n \nMEMBERSHIP  \n \nWork group Leadership: The COVID -19 Immunization s WG is  chaired by one of the ACIP, CDC \nmembers  appointed to serve as Special Government Employees. The Workgroup Lead (WGL ) is \na federal employee, identified  by the Immediate Office of the Director in consultation with  the \nappropriate CDC program . The WG Chair , in consultation with the WGL, ACIP, CDC DFO,  \ndetermine s the WG ’s membership and work priorities and deliverables  to the full committee .   \n \nWorkgroup Membership:  The COVID -19 Immunizations  WG  is comp osed of  experts who are \nappointed based on their professional, scientific, technical, or other expertise.  They are experts \nwho are regarded as an authority or a practitioner of unique competence and skill by other \npersons in the ir profession, or occupation. Upon request, HHS f ederal agencies named in the \nACIP charter may  also appoint members to serve on WGs. The COVID -19 Immunization s WG \nwill be comp osed of members from a variety of disciplines . The WG will engage with the \nfollowing disciplines on WG activities to : \n \n• Public health science and practice;  \n• Public health policy development, analysis, and implementation, including development and \nexecution of immunization programs for children and adults; \n• Clinical and medical practice , and patience -care experience;  \n• Epidemiology;  \n• Molecular biology;  \n• Immunology;  \n• Virology;  \n• Drug  and vaccine safety ; and  \n• Consumer perspectives and/or social and community aspects of immunization programs \n \nDue to the complexity and variability of information to be gathered, additional external subject \nmatter experts may  also be invited to provide data and presentations to the WG and answer \nquestions during COVID -19 Immunization WG  meetings on an ad hoc basis. Such additional \nexternal subject matter experts will not be members of the WG  and will not participate in any \ndeliberations or WG  discussions. \n \n \nMEETINGS, ADMINISTRATION, and TIMELINES  \n \n1.\n Administrative Oversight:  The WGL  will work with the WG Chair to arrange meetings, \ndocument meeting proceedings, and report to the ACIP on the COVID -19 Immunization WG’s \nactivities and  findings.   \nPage 5 of 6 \n 2. Meeting frequency  and location:  The COVID -19 Immunization  WG will meet on an as needed \nbasis as determined by the WG Chair and WGL . All COVID -19 Immunization WG meetings are \nconvened virtual ly via teleconference.  \n3. M eeting structure :  In addition to the WGL,  at least two ACIP Special Government Employee \nmember s (one of whom serves as the COVID -19 Immunization WG  Chair) must be present at \neach meeting for a quorum.  An agenda, relevant publications, and background documents will \nbe circulated as read ahead material prior to each meeting.  \n4. C onflicts of Interest :  WG  members will complete an  ACIP WG  Agreement and Conflict of \nInterest Certification  process  prior to participation on the WG.  They will consent to abide by \nseveral guiding principles and disclose interests (e.g., employment, special interests, grants, or contracts) that a reasonable person could view as conflicts or potential conflicts of interest with their COVID -19 Immunization  WG participation.  Members will also disclose any potential \nconflicts of interest before each meeting.  If a COVID -19 Immunization s WG member indicates \na potential or actual conflict of interest, the ACIP , CDC DFO  in consultation with the WGL  will \nreview and make a determination as to  whether the individual must recuse themselves from \nparticipating  in WG discussions that implicate such a conflict -of-interest concern.   \n5. C\nonfidentiality :  The discussions of the COVID -19 Immunization s WG  may include information \nthat is unpublished, protected, privileged, or confidential. WG deliberations, including policy options under consideration by the WG , are also considered confidential.  Information of this \nnature must not be disseminated, distributed, or copied to persons not authorized to receive such information.  When these types of information are distributed, the person/s presenting will identify the information as such, so all members are duly informed; and written materials shall be clearly marked as such.   Unlike ACIP meetings, which are open to the public, COVID-19 \nImmunizations WG teleconferences are not subject to the open meeting requirements of the Federal Advisory Committee Act or the GSA Final Rule; data presented during these meetings/teleconferences are often proprietary and should not be distributed to people other than approved COVID -19 Immunizations WG members.   \n6. C\nDC Staff Involvement:  CDC staff do not serve as members of the COVID -19 Immunization s \nWG but may provide administrative support and technical expertise to ACIP WGs, bringing \nsubject matter expertise and current professional focus in areas relevant to the goas of the COVID-19 Immunizations  WG.  Consultation or informational  presentations by CDC staff will \nbe transparent and evident to minimize the risk of, or the appearance of, undue influence that would compromise the independence of the WG.  The ACIP , CDC  DFO and WGL of COVID -\n19 Immunizations  WG, in consultation with the Chair of the COVID -19 Immunizations WG, \nwill monitor the interaction between the WG and the agency  staff  to ensure that the WG  \nactivities and work products are appropriate and that there is not undue influence by the CDC or by any special interest group on the activities or  work products of the WG.  \n7. T\nimelines:  ACIP WGs are  established when needed and  terminated once the activities and work \nproducts stated in the terms of reference have been completed  and the WG’s charge has been \nfulfilled .  \n8. S ubject content: Findings and opinions of the COVID -19 Immunizations  WG members will be \ndiscussed at meetings.  The COVID -19 Immunizations  WG’s findings will be presented to ACIP \nfor consideration for action (discussion, deliberation and decision).   \n9. W orkgroup Meeting Summaries: Meeting minutes will be created to capture the information \ngathered during each COVID -19 Immunizations  WG meeting and teleconference.   \nPage 6 of 6 \n 10. Workgroup findings : The COVID-19 Immunizations  WG will present findings (briefing \ndocuments, background materials, presentations) to ACIP for consideration and deliberation in a \npublic meeting.  Final versions of all slides presented at the ACIP meeting will be posted on the ACIP website following the meeting and included in the committee’s official records.   \n11. Workgroup Record Keeping: All CDC FACA committees, subcommittees, and WGs are subject \nto the Federal Records Act.  All records will be uploaded in the Federal Advisory Committee Management Portal.  The summary report and other WG documents will become part of the ACIP’s official re cords as required by GENERAL RECORDS SCHEDULE 6.2: Federal \nAdvisory Committee Records \n \nRECORDKEEPING and REPORTING  \n \nThe WG  Chair and WG L will present findings/outcomes/observations /recommendations  to the \nACIP  parent committee  for discussion, deliberations, further development of recommendations \nand vote in an open public forum.  Approved ACIP recommendations adopted by the CDC Director wil l be published in the Morbidity and Mortality Weekly Report (MMWR).  In addition, \napproved AC IP recommendations will be included in the AC IP meeting minutes and annual \nreport.", "summary": "Page 1 of 6     Ad visory Committee on Immunization Practices ,  Centers for Disease Control and Prevention (ACIP, CDC)   COVID-19 Immunization Workgroup    Terms of R eference   UPDATED:  August 20, 2025    P URPOSE     T his document defines the activities, membership, and administrative requirements associated  with the establishment of a COVID-19 Immunization Workgroup  under the Advisory  Committee on Immunization Practices, Centers for Disease Control and Prevention (ACIP,  CDC).   ACIP…", "source_url": "https://www.cdc.gov/acip/our-work/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/COVID19-TOR-508.pdf", "case": "acip", "sub_case": "other", "tags": ["acip", "cdc", "vaccines", "other"], "page_count": 6}
{"title": "hpv tor 508", "content": "Page 1 of 7 \n  \nAdvisory Committee on Immunization Practices  (ACIP)  \nCenters for Disease Control and Prevention (CDC)  \nHuman Papillomavirus (HPV ) Vaccine Workgroup   \nTerms of R eference  \nUPDATED:  December 18 , 2025 \n \nPURPOSE  \n \nThis document defines the activities, membership, and administrative requirements associated \nwith the establishment of a Human Papillomavirus (HPV ) Vaccine Workgroup  under the \nAdvisory Committee on Immunization Practices, Centers for Disease Control and Prevention (ACIP, CDC).   ACIP utilizes subgroups of the Committee, known as Workgroups (WGs), to \nreview relevant published and unpublished data , and clinical and scientific knowledge, and \ndevelop options for presentation to the full ACIP  parent committee  during its public meetings to \nfacilitate discussion, deliberation , and development of recommendations.  ACIP WGs are \nintended to augment the effectiveness of ACIP.  The direction, focus, and pace of both ACIP and the individual WGs are guided by CDC and HHS policies and priorities,  as well as the need for \nexpert input to inform development of CDC immunization policy.  ACIP WGs play a key \nscientific role supporting immunization  recommendations.  The HPV Vaccines  WG has been \nspecifically established  to review data , as well as clinical and scientific knowledge on HPV \nvaccine s and their role in preventing infection and cancer and their effect on prevalence and \ncarcinogencity of subtypes, to help develop HPV immunization policy options  for ACIP \nconsideratio n to formulate recommendations to the Director of the CDC.  \n \nFor purposes of this document, “ Immunization ” refers to vaccines and other antibody protective \nproducts  used to prevent disease such as immunoglobulins .  \n \nBACKGROUND  \n \nHPV is a common virus spread through intimate skin- to-skin contact. Although most HPV \ninfections become undetectable within two  years, some HPV infections will persist and can \ncause cancers in women and men.  In the United States, HPV vaccination is currently \nrecommended in early adolescence to protect against HPV infection. A 9 -valent HPV vaccine , \n9vHPV , is the only HPV vaccine currently available in the United States. This vaccine  targets  \nnine HPV types (HPV 6, 11, 16, 18, 31, 33, 45, 52, and 58) that  cause the majority of cervical \nand other HPV -related  cancers and anogenital warts.   \n An ACIP HPV Vaccine Work Group met almost continuously from 2005 through 2019 to address policy for new vaccines and new FDA indications.  The work of the  HPV Vaccine WG \nwas reconvened in July 2024 to review and discuss the number of vaccine doses in the recommended HPV vaccination series and the recommended  age for routine HPV vaccination.  \nThe HPV Vaccine WG will continue this work and, per ACIP charter,  will also conduct a \ncomprehensive review of the cumulative data, knowledge , and evidence regarding the efficacy, \neffectiveness and the safety of the HPV vaccine.  \n \nPage 2 of 7 \n In accordance with the  21st Century Cures Act (PL 114-255), ACIP shall also , as appropriate, \nconsider new vaccines or new indications at its next regularly scheduled meeting after licensure; \nif the Committee defers making a recommendation, it will provide an update on the status of its \nreview. Ad ditionally, ACIP shall make recommendations in a timely ma nner for vaccines that \nare designated as breakthrough interventions or could be used in a public health emergency. In case of any new HPV immunizations, the ACIP parent committee requests that the HPV Vaccine WG include consideration of the new immunizations  to assist the parent committee in \nimplementing its 21\nst Century Cures Act requirements.      \n The purpose of this HPV Vaccine WG  is to review available data, as well as clinical and \nscientific knowledge, to support the development of recommendations for ACIP consideratio n \nthat are used to advise the Director of the CDC.  \n The HPV Vaccine WG will also assist and support the A CIP parent committee , in accordance \nwith Section 1928 of the Social Security Act (42 USC 1396s) , to be able to establish and \nperiodically review and, as appropriate, revise the list of immunization s for administration to \nchildren and adolescents eligible to receive immunizations  through the Vaccines for Children \nProgram, along with schedules regarding the appropriate dose and dosing intervals , and \ncontraindications to administration of the pediatric immunization .  \n  \nTOPICS UNDER DISCUSSION BY THE WORKGROUP  \n \nThe following topics relevant to  a comprehensive review of the efficacy, effectiveness and safety \nof the HPV vaccine, as well as to specific vaccination policies regarding the use of HPV vaccine \nand effective control of HPV in fection and related disease in the population of the United States \nwill be under discussion in the HPV Vaccine WG in multi- year efforts and include , for \npresentation to the parent committee for its deliberation and development of recommendations to \nCDC, evaluation of:   \n1) HPV vaccination schedules with fewer  doses; \n \n2) Wording of the age for routine HPV vaccination ; and  \n \n3) Draft p olicy recommendations following a comprehensive review of the cumulative \nscientific and clinical data, knowledge, and evidence regarding the efficacy, \neffectiveness, and the safety of the HPV vaccine. This includes assessment of the long \nterm effect s of HPV vaccination programs on population level incidence (per subtype), \nmorbidity and mortality of cervical cancer.  \n \nDESCRI PTION of WORKGROUP  ACTIVITIES   \nThe following activities provide a framework for the HPV Vaccine  WG multi -year efforts , which \nmay involve data requests from other Federal and private partners , for development of \nPage 3 of 7 \n presentations to the parent ACIP for its deliberations as it develops recommendations to the CDC \nDirector:  \n1. Summarize and review the cumulative data on temporal trends in the U.S. and other countries  \nof HPV infection, precancers, cervical cancer incidence ; other HPV attributable outcomes; \nand mortality per different age groups and how they potentially correlate with evolving \nvaccination rates and screening policies.  \n \n2. Summarize and review , using existing systematic reviews, where possible, the cumulative \ndata and knowledge regarding vaccine efficacy and effectiveness in  relation  to cervical \ncancer and surrogate outcomes, including a meta -analysis of clinical trials and observational \nstudies.  \n \n3. Summarize and review the cumulative data and knowledge regarding vaccine safety and related adverse events, including VAERS source and other safety data and meta -analysis of \nclinical trials and observational studies.  \n \n4. Characterize the nature of the safety reports in men and women and timing of the report post vaccination with the first and second dose.   \n \n5. Summarize and review existing data and knowledge regarding the potential toxicity of HPV vaccine, adjuvants, and potential contaminants and/or impurities.  \n \n6. Summarize and review existing knowledge related to the efficacy, eff ectiveness and safety of \nHPV vaccination when given to individuals with prior exposure to HPV infections.  \n \n7. Summarize and review the existing data on potential HPV type replacement (i.e., increase in \noncogenic types not targeted by HPV vaccine, after introduction of HPV vaccination \nprograms , as well as data and knowledge related to the potential impact of vaccination rates.   \n8. Review  and summarize existing  data, including published and as available and appropriate,  \nunpublished research, as well as clinical knowledge, related to the efficacy, effectiveness, \nand immunogenicity of HPV vaccination with fewer than two doses in individuals aged 9 \nthrough 14 years. \n \n9. Review and summarize existing data  including published and, as available and appropriate,  \nunpublished research, as well as clinical knowledge related to the efficacy, effectiveness, and \nimmunogenicity of HPV vaccination with fewer than three  doses in individuals to inform \nvaccination recommendations for persons aged 15 years and older. \n \n10. Review programmatic data on age at vaccination in the United States.  \n \n11. Develop HPV vaccination policy options for presentation to  and deliberation by, the ACIP  \nparent committee . \nPage 4 of 7 \n Overall, the HPV Vaccine WG will prepare information for the ACIP members to enable them \nto:  \n• Advise on population groups and/or circumstances in which a vaccine or related agent is recommended.  \n• Provide recommendations on contraindications and precautions for use of the vaccine and \nrelated agents and provide information on recognized adverse events.  \n• Provide recommendations that address the general use of vaccines and if applicable, \nimmune globulin preparations as a class of biologic agents, use of specific antibody products for prevention of infectious diseases, and special situations or populations that may warrant modification of the routine recommendations.  \n• Support committee deliberations on use of immunization to control disease including consideration of disease epidemiology and burden of disease, immunization safety, immunization efficacy and effectiveness, the quality of evidence reviewed, economic analys es, medical ethics, and implementation issues including informed consent \nlanguage. \n• Revise or withdraw their recommendation(s) regarding a particular immunization should new information on disease epidemiology, immunization effectiveness or safety, economic considerations, or other data become available.  \n \n \nMEMBERSHIP  \n \nWorkgroup Leadership:  The HPV Vaccine WG is  chaired by a member of ACIP committee . The \nWorkgroup Lead  (WG L) is a federal employee, identified  by the ACIP parent committee \nDesignated Federal O fficial (DFO) ( within the Immediate Office of the Director) in consultation \nwith the relevant CDC program s. The ACIP DFO will determine wh ich roles and responsibilities \nwill be further assigned, as appropriate, to the WGL, who will then be responsible for carrying \nthem out .  The WG Chair , in consultation with both the WG L and the DFO,  establishes the \nWG’s membership , work priorities , and deliverables  for presentation to the full committee .   \n \nWorkgroup Membership:  The HPV Vaccine  WG  is comp osed of experts who are appointed \nbased on their professional, scientific, technical, or other expertise.  They are experts who are \nregarded as an authority or a practitioner of unique competence and skill by other individuals in \ntheir profession or occupation. Upon request, HHS f ederal agencies name d in the ACIP charter \nmay also appoint members to serve on WGs. The HPV Vaccine  WG will be comp osed of \nmembers  from a variety of disciplines. The HPV Vaccine WG will engage with the following \ndisciplines on WG activities : \n \n• Public health science and practice ;  \n• Public health policy development, analysis, and implementation, including development and \nexecution of immunization programs for children and adults; \n• Clinical and medical practice , and patient- care experience;  \n• Epidemiology;  \n• Immunology;  \n• Virology;  \n• Neurology; \nPage 5 of 7 \n • Oncology; \n• Pathology; \n• Toxicology;  \n• Drug  and vaccine safety;  \n• Medical ethics; and  \n• Consumer perspectives and/or social and community aspects of immunization programs \n \nDue to the complexity and variability of information to be gathered, additional external subject \nmatter experts may also be invited to provide data and presentations to the HPV Vaccine WG \nand answer questions during HPV Vaccine WG meetings on an ad hoc basis. Such additional \nexternal subject matter experts will not be members of the HPV Vaccine WG  and will not \nparticipate in any deliberations or HPV Vaccine WG  discussions.  \n \n \nMEETINGS, ADMINISTRATION, and TIMELINES  \n \n1. Administrative Oversight:  The WG L will work with the WG Chair to arrange meetings, and \ndocument meeting proceedings  and may provide presentations about the WG activities and \nfindings to the ACIP.  Staff from WG L’s program may be assigned to assist with some of the \nWG’s administrative activities including notetaking and required record keeping.  \n \n2. Meeting frequency and location :  The HPV Vaccine  WG will meet  on an as needed basis as \ndetermined by the WG Chair and WGL. All HPV Vaccine  WG meetings are convened virtual ly \nvia teleconference.  \n \n3. Meeting structure :  In addition to the WGL, at least two ACIP parent committee members  (one \nof whom serves as the HPV Vaccine WG  Chair) must be present at each meeting for a quorum.  \nAn agenda, relevant publications, and background documents will be circulated as read ahead \nmaterial prior to each meeting.  \n \n4. Conflicts of Interest :  HPV Vaccine WG  members will complete an  ACIP WG  Agreement and \nConflict of I nterest Certification  process prior to participation on the HPV Vaccine WG.  The \nWGL will screen for conflict- of-interest declarations and share any conflicts that need to be \nelevated to the DFO/ACIP Secretariat.   The ACIP parent committee DFO in collaboration with \nthe WGL  will work with the Office of Strategic Business Initiatives, Federal Advisory \nCommittee Act Program and the Office of the General Counsel (OGC) as needed, to mitigate any conflicts identifie d.  HPV Vaccine WG members will consent to abide by guiding principles and \ndisclose interests (e.g., employment, special interests, grants, or contracts) that a reasonable person could view as conflicts or potential conflicts of interest with their HPV Vaccine  WG \nparticipation.  Members will also disclose any potential conflicts of interest before each meeting.  If an HPV Vaccine  WG member indicates a potential or actual conflict of interest, the DFO will \nreview and make a determination as to  whether the individual must recuse themselves from \nparticipating  in HPV Vaccine WG discussions that implicate such a conflict -of-interest concern.   \n \nPage 6 of 7 \n 5. Confidentiality :  The discussions of the HPV Vaccine  WG  may include information that is \nunpublished, protected, privileged, or confidential . HPV Vaccine W G deliberations, including \npolicy options  under consideration by the HPV Vaccine WG , are also considered confidential .  \nInformation of this nature must not be disseminated, distributed, or copied to persons not \nauthorized to receive such information.  When these types of information are distributed, the person/s presenting will identify the information as such, so all members are duly informed; and written materials shall be clearly marked as such.   Unlike ACIP parent committee meetings, \nwhich are open to the public, HPV Vaccine  WG teleconferences are not subject to the open \nmeeting requirements  of the Federal Advisory Committee Act or the GSA Final Rule ; data \npresented during these meetings/teleconferences are often proprietary and should not be distributed to people other than approved HPV Vaccines WG members.   \n \n6. CDC Staff Involvement:   CDC staff do not serve as members of the HPV Vaccine  WG  but may \nprovide administrative support and technical expertise to ACIP WG, bringing subject matter expertise and current professional focus in areas relevant to the goal s of the HPV Vaccine WG.  \nConsultation or information al presentations by CDC staff will be transparent and evident to \nminimize the risk of, or the appearance of, undue influence that would compromise the independence of the WG.  The ACIP , CDC parent committee DFO and WG L of the HPV \nVaccine WG, in consultation with the Chair of the HPV Vaccine  WG, will monitor the \ninteraction between the WG and the agency staff  to ensure that the WG  activities and work \nproducts are appropriate and that there is not undue influence by the CDC or by any special interest group on the activities  or work products  of the  WG .  \n \n7. Timelines :  ACIP WGs are established when needed and terminated once the activities and work \nproducts stated in the terms of reference have been completed  and the  WG ’s charge has been \nfulfilled .  \n \n8. Subject content:  Findings and opinions of the HPV Vaccine  WG members will be discussed at \nmeetings.  The HPV Vaccine  WG’s findings will be presented to the ACIP  parent committee  for \nconsideration for action (discussion, deliberation and decision , and recommendations ).   \n \n9. Workgroup Meeting Summaries:  Meeting minutes will be created to capture the information \ngathered during each HPV Vaccine  WG meeting and teleconference.   \n \n10. Workgroup findings : The HPV Vaccine  WG will present findings (briefing documents, \nbackground materials, presentations) to the ACIP  parent committee  for consideration and \ndeliberation in a public meeting. Final versions of all slides presented at the ACIP parent committee meeting will be posted on the ACIP website following the meeting and included in \nthe committee’s official records.   \n \n11. Workgroup Record Keeping: All CDC FACA committees, subcommittees, and WGs are subject \nto the Federal Records Act. All records will be uploaded in the Federal Advisory Committee Management Portal. The summary report of WG meeting activities and other WG documents will become part of the ACIP’s official records as required by GENERAL RECORDS SCHEDULE 6.2: Federal Advisory Committee Records . \n \nPage 7 of 7 \n RECORDKEEPING and REPORTING  \n \nThe WG  Chair and WG L, WG members and other experts will present \nfindings/outcomes/observations to the ACIP  parent committee  for discussion, deliberations, \nfurther development of recommendations, and vote in an open public forum. Approved ACIP \nrecommendations adopted by the CDC Director wil l be posted on CDC’s ACIP website and also \npublished in the Morbidity and Mortality Weekly Report (MMWR).  In addition, approved ACIP recommendations will be included in the ACIP meeting minutes  and annual report.", "summary": "Page 1 of 7     Advisory Committee on Immunization Practices  (ACIP)   Centers for Disease Control and Prevention (CDC)   Human Papillomavirus (HPV ) Vaccine Workgroup    Terms of R eference   UPDATED:  December 18 , 2025    PURPOSE     This document defines the activities, membership, and administrative requirements associated  with the establishment of a Human Papillomavirus (HPV ) Vaccine Workgroup  under the  Advisory Committee on Immunization Practices, Centers for Disease Control and…", "source_url": "https://www.cdc.gov/acip/our-work/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/hpv-tor-508.pdf", "case": "acip", "sub_case": "other", "tags": ["acip", "cdc", "vaccines", "other"], "page_count": 7}
{"title": "influenza tor 508", "content": "Page 1 of 7 \n Advisory Committee on Immunization Practices  (ACIP)  \nCenters for Disease Control and Prevention (CDC)  \nInfluenza  Immunization Workgroup   \nTerms of R eference  \nDRAFT: December 18 , 2025 \n \nPURPOSE  \n This document defines the activities, membership, and administrative requirements associated with the establishment of a n Influenza  Immunization Workgroup  under the Advisory \nCommittee on Immunization Practices, Centers for Disease Control and Prevention (ACIP, CDC).   ACIP utilizes subgroups of the Committee, known as Workgroups (WGs), to review \nrelevant published and unpublished data , and clinical and scientific knowledge, and develop \noptions for presentation to the full ACIP  parent committee  during its public meetings to facilitate \ndiscussion, deliberation and development of recommendations.  ACIP WGs are intended to enhance the effectiveness of ACIP.  The d irection, focus, and pace of both ACIP and the \nindividual WGs are guided by CDC and HHS policies and priorities, and by the need for expert input to inform development of CDC immunization policy. ACIP WGs serve a key scientific \nrole in support of immunization  recommendations.  The Influenza Immunization  WG has been \nspecifically established  to review data , as well as clinical and scientific knowledge on existing \nand developmental- stage influenza immunization s, to help develop influenza  immunization \npolicy options for ACIP consideratio n to formulate recommendations to the Director of the CDC.  \n For purposes of this document, “i mmunization ” refers to vaccines and other antibody protective \nproducts to prevent disease, e.g., immunoglobulins.  \n \nBACKGROUND  \n \nInfluenza  is a disease caused by the influenza A and B virus es. There are other upper respiratory \nviruses and pathogens such as respiratory syncytial virus (RSV), rhinoviruses, mycoplasma, \nSarbecoviruses, beta coronaviruses , and human metapneumoviruses that are associated with \nclinical signs and symptoms similar or identical to influenza. Both i nfluenza virus es and these \nother pathogens contribute to the overall burden of influenza- like illness (ILI).  F or some \npatients, influenza and other ILI can be severe, causing significant morbidity and mortality , and \nare a frequent contributing cofactor to morbidity and mortality in some populations with \nadditional risk factors . Currently , there are multiple  vaccine manufacturers employing a wide \nrange of manufacturing, formulation , and adjuvant technologies to produce i nfluenza vaccines \nfor the United States .   \nThe specific virus components for the 2025–2026 season include: \nAn A/Victoria/4897/2022 (H1N1)pdm09-like virus (for egg- based vaccines) or an \nA/Wisconsin/67/2022 (H1N1)pdm09- like virus (for cell- or recombinant -based vaccines)  \nAn A/Croatia/10136RV/2023 (H3N2)-like virus (for egg- based vaccines) or an A/District of \nColumbia/27/2023 (H3N2)- like virus (for cell- or recombinant- based vaccines)  \nPage 2 of 7 \n A B/Austria/1359417/2021 (B/Victoria lineage) -like virus  \nFor those manufacturing platforms employing either chick embryo or mammalian cell -based \nantigen production, the seed virus representing the annually selected influenza strain(s) requires  \nadaptation from the circulating version infecting humans to support efficient reproduction in the \nrelevant manufacturing platform supporting viral replication.  In some cases, this adaptation may \nintroduce partial antigenic mismatch relative to the parental human circulating viruses.  For other \nplatforms such as baculovirus- based manufacturing, it may be that this form of seed virus protein \nsequence drift relative to parental strain is minimized, but these platforms may yield antigens \nthat diverge in criti cal glycosylation patter ns relative to parental human circulating viruses.  The \nsignificance,  or lack thereof , of influenza antigens glycosylated with insect patterns rather than \nmammalian patterns is not well characterized.  \nNew formulations , compositions, or technologies  for use in influenza  vaccine s are actively being  \ndeveloped, with a specific emphasis on a universal influenza vaccin e.  These may require \nregulatory  (by the appropriate entities)  and ACIP safety and efficacy  and/or effectiveness review \nin the foreseeable future.  \nAccording to the 21st Century Cures Act (PL 114- 255), ACIP shall also, as appropriate, consider \nnew vaccines or new indications at its next regularly scheduled meeting after licensure . If the \nCommittee defers making a recommendation, it will provide an update on the status of its \nreview. Ad ditionally, ACIP shall make recommendations in a timely ma nner for vaccines that \nare designated as breakthrough interventions or could be used in a public health emergency.  The purpose of this WG  is to review available data, as well as clinical and scientific knowledge, \nto support the development of vaccine and related product clinical use recommendations for ACIP parent committee consideratio n, which may then elect to advise  the Director of the CDC  \nconcerning those recommendations . \n In accordance with the ACIP Charter, t he Influenza  Immunization WG will prepare information \nfor the ACIP  parent committee  members to enable them to:  \n• Advise on population groups and/or circumstances in which one or more influenza  \nvaccine s or related agent s are recommended.  \n• Provide recommendations on contraindications and precautions for the use of influenza  \nvaccine s and related agents , and provide information on recognized adverse events.  \n• Provide  recommendations that address the general use of influenza v accines and \nimmune -globulin preparations as a class of biologic agents, use of specific antibody \nproducts for prevention of influenza infection- related infectious diseases, and special \nsituations or populations that may warrant modification of the routine recommendations.  \n• Support c ommittee deliberations on the use of immunization  to control disease , including \nconsideration of disease epidemiology and burden of disease, immunization  safety, \nimmunization  efficacy and effectiveness, the quality of evidence reviewed, economic \nanalyses, and implementation issues.  \n• Revise or withdraw , as warranted,  their recommendation(s) regarding a particular \ninfluenza immunization  or related product as new information on disease epidemiology, \nPage 3 of 7 \n immunization  effectiveness or safety, economic considerations, or other data that \nbecomes available.  \n• Differentiate and provide differentiated data summaries regarding the use of specific \ninfluenza vaccines in various risk groups, and facilitate modified use recommendations as appropriate or necessary concerning specific influenza vaccines or related products and technologies. \n The WG will also assist and support A CIP, i n accordance with Section 1928 of the Social \nSecurity Act,  [42 U.S.C. Section 1396s ], to be able to establish and periodically review and, as \nappropriate, revise the list of immunization s for administration to children and adolescents \neligible to receive immunizations  through the Vaccines for Children Program, along with \nrecommended schedules concerning the appropriate dose and dosing interval, and contraindications to administration of pediatric immunization s.  \n The WG will engage external subject matter experts, as needed, to support  development of \nmaterials for presentation to the WG and/or parent committee for its deliberations . \n  \nTOPICS UNDER DISCUSSION BY THE WORKGROUP  \n \nIn accordance with the ACIP Charter and in a multi -year effort, the Influenza Immunization WG \nmembers will work with expert consultants as appropriate and in accordance with FACA \nstatutory requirements and policies, to prepare information for presentation to and deliberation \nby the parent ACIP committee in developing their recommendations . In particular, the following \ntopics and related activities relevant to  influenza immunization  for effective control of i nfluenza \nA and/or B- related  disease in the civilian population of the United States will be considered  as a \nframework  for and/or undertaken by the Influenza WG in multi -year effort s:   \n1) Conduct and/or review r isk-benefit and cost -benefit data for, and/or analyses of , existing and \nnewly -licensed  influenza vaccines, and their administration  schedules, to inform the parent \ncommittee’s deliberations on vaccine use recommendations according to age-group, major \nrisk factors , and health status.  \n2) Identify critical gaps in  existing scientific  and clinical  knowledge and CDC monitoring \nmethods related to the safety , efficacy /effectiveness,  immunogenicity, and long- term immune \nsystem impacts  of influenza vaccines  to inform the parent committee’s deliberations on \ndevelopment of policy recommendations and to identify further analyses and research to be \nrecommended to  CDC for its consideration and CDC potential advice to other federal \nagencies and the scientific community  to conduct. \n3) Review and summarize data, clinical and scientific knowledge related to short and long- term \nadverse events associated with influenza vaccines  to present to the parent committee for its \ndeliberations in  identify ing precautions and contraindications recommendations.  \n4) Review and summarize data for presentation to the parent committee on the long- term \nimmunological effects of repeated annual influenza vaccination as a function of risk group \nand strain variability or type (drift/shift).  \nPage 4 of 7 \n  \nDESCRI PTION of WORKGROUP  ACTIVITIES   \nThe following activities provide a framework for the Influenza Immunization WG multi- year \nefforts , which may involve data requests from the FDA and other f ederal agencies and private \npartners , for development of presentations to the parent ACIP for its deliberations as it develops \nrecommendations to the CDC Director:    \n1. Review  and summarize existing  data including published and unpublished research and \nclinical knowledge related to the safety, effectiveness, and immunogenicity of influenza \nvaccines authorized or approved in the U nited S tates. \n2. Summarize literature review s of the epidemiology of influenza disease and infection . \n3. Assess the benefit -risk balance for administration  of influenza immunization products co -\nadministered with other vaccinations. \n4. Identify areas where additional data and research  are needed to inform influenza \nimmunization recommendations to be developed by ACIP. \n5. Annually review and develop updat es of U.S. seasonal influenza  immunization  policy \nrecommendations. \n6. Review and summarize the existing clinical and scientific information concerning the role of \ninnate, adaptive innate, adaptive cellular , and adaptive humoral immune responses associated \nwith different influenza vaccines, adjuvants, and correlates of protection associated with \ninfluenza vaccination. \n7. Review and  summarize the existing clinical and scientific information , and gaps in the \nexisting knowledge, including from the FDA and other federal agencies, as well as academic \nstudies, concerning the impact of repeated influenza vaccination including immunological \neffects such as immune imprinting, “ original antigenic sin ,” and related phenomena.  \n8. Review and s ummarize the existing clinical and scientific information , and  identify and \naddress gaps in the existing knowledge regarding both antigenic sequence mismatch , as well \nas glycosylation mismatch , in existing immunization products and their health impacts  to \ninform immunization recommendations. \n9. Review and summarize  the existing scientific knowledge and gaps, regarding the cumulative \nshort- and long- term impact of repeated annual seasonal influenza vaccination  (including \nboosting in young children’s first season), including non- specific effects (e.g., IgG4 class \nswitching, immune imprinting, viral evolution under leaky immunizations ) to help inform \nimmunization recommendations.  \n10. Examin e the impact of Influenza A and B immunization  on influenza  and all-cause deaths, \nhospitalizations, and disability to inform immunization recommendations . \n11. Analyze existing data and scientific knowledge regarding cardiovascular, thrombotic, \nneurological , immunological, and othe r serious adverse events potentially caused  and averted \nby influenza  immunization .  \n12. Review, analyze, and summarize available data concerning the safety and effectiveness of influenza immunization of the elderly , including the interaction between influenza vaccines \nand immunosenescence, and both innate and adaptive immunity. \nPage 5 of 7 \n 13. Review and s ummarize available data, information , and gaps regarding long- term repeated \nInfluenza vaccination  effects from scientific literature  and clinical experi ence associated with \ninfluenza  immunization products and influenza  infection  to inform policy  recommendations.   \n14. Map existing influenza  immunization  policies in countries around the world and how they \ncompare to U .S. vaccine policy. \n15. Analyze existing data and scientific knowledge related to the safety of influenza \nimmunization  during pregnancy, including both potential teratogenic effects and potential \nbeneficial effects for the newborn . \n \nMEMBERSHIP  \n \nWorkgroup Leadership:  The Influenza  Immunization  WG is  chaired by one of the ACIP, CDC \nparent committee members appointed to serve as Special Government Employees. The \nWorkgroup Lead (WGL ) is a federal employee, identified  by the Immediate Office of the \nDirector in consultation with  the appropriate CDC program . The WG Chair , in consultation with \nthe WGL, ACIP  CDC Designated Federal Offi cial (DFO), determine s the WG ’s membership and \nwork priorities and deliverables to the full committee . The DFO may further assign  some of the  \nDFO- related roles and responsibilities , as appropriate,  to the WGL.     \n \nWorkgroup Membership:  The Influenza Immunization  WG is comp osed of  experts who are \nappointed based on their professional, scientific, technical, or other expertise.  They are  experts \nwho are regarded as an authority or a practitioner of unique competence and skill by other \npersons in the ir profession, or occupation. Upon request, HHS f ederal agencies name d in the \nACIP charter may  also appoint members to serve on WG s. The Influenza  Immunization WG will \nbe composed of members from a variety of disciplines. The WG will engage with the following \ndisciplines on WG activities : \n \n• Public health science and practice ;  \n• Public health policy development, analysis, and implementation, including development and \nexecution of immunization programs for children and adults; \n• Clinical and medical practice , and patien t-care experience;  \n• Epidemiology;  \n• Molecular biology;  \n• Immunology;  \n• Virology;  \n• Diagnostics and correlates of protection;  \n• Drug  and vaccine safety;  \n• Bioethics; and  \n• Consumer perspectives and/or social and community aspects of immunization programs \n \nDue to the complexity and variability of the information to be gathered, additional external \nsubject matter experts may also be invited to provide data and presentations to the WG and \nanswer questions during Influenza  Immunization WG  meetings on an ad -hoc basis. Such \nPage 6 of 7 \n additional external subject matter experts will not be members of the WG  and will not participate \nin any deliberations or WG discussions.  \n \n \nMEETINGS, ADMINISTRATION, and TIMELINES  \n1. Administrative Oversight:  The WGL  will work with the WG Chair to arrange meetings, \ndocument meeting proceedings, and report to the ACIP on the Influenza  Immunization WG’s \nactivities and  findings.   \n2. Meeting frequency and location :  The Influenza  Immunization WG will meet on an as needed \nbasis as determined by the WG Chair and WGL . All Influenza Immunization WG meetings are \nconvened virtual ly via teleconference.  \n3. Meeting structure :  In addition to the WGL,  at least two ACIP parent committee  member s (one \nof whom serves as the Influenza  Immunization WG  Chair) must be present at each meeting for a \nquorum.  An agenda, relevant publications, and background documents will be circulated as \nread-ahead mat erial before each meeting.  \n4. Conflicts of Interest :  WG  members will complete an ACIP WG  Agreement and C onflict of \nInterest Certification  process before  participation on the WG.  The WGL will screen for conflict \nof interest declarations and share any conflicts with the ACIP Secretariat.  The ACIP Secretariat /DFO, in collaboration with WGL will work with the Office of Business Initiatives \n(OSBI)  ethics officials and the Office of General Counsel (OGC), as needed, to resolve any \nconflicts  that the WGL  identifie d.  WG members  will consent to abide by several guiding \nprinciples and disclose interests (e.g., employment, special interests, grants, or contracts) that a \nreasonable person could view as conflicts or potential conflicts of interest with their Influenza  \nImmunization  WG participation.  Members will also disclose any potential conflicts of interest \nbefore each meeting.  If an Influenza Immunization  WG member indicates a potential or actual \nconflict of interest to the WGL , the WGL or designee will  forward  any conflicts to the DFO to  \ndetermine  whether the individual must  recuse themselves from participating  in WG discussions \nthat implicate such a conflict -of-interest concern. If needed, the DFO will engage OSBI and \nOGC to assist with making COI determination.   \n5. Confidentiality : The discussions by the Influenza  Immunization  WG  may include information \nthat is unpublished, protected, privileged, proprietary, or confidential. WG deliberations, including policy options under consideration by the WG , are also considered confidential.  \nInformation of this nature must not be disseminated, distributed, or copied to, and/ or described or \ndiscussed with,  persons not authorized to receive such information.  When these types of \ninformation are distributed, the person/s presenting will identify the information as such, so all members are duly informed; and written materials shall be clearly marked as such.   Unlike ACIP  \nparent committee  meetings, which are open to the public, Influenza Immunization WG \nteleconferences are not subject to the open meeting requirements of the Federal Advisory Committee Act or the GSA Final Rule; data presented during these meetings/teleconferences are often proprietary and should not be distributed to people other than approved Influenza Immunization  WG members.   \n6. CDC Staff Involvement:  CDC staff do not serve as members of the Influenza Immunization  WG  \nbut may provide administrative support and technical expertise to ACIP WGs, bringing subject matter expertise and current professional focus in areas relevant to the goal s of the Influenza \nImmunization  WG.  C onsultation or information al presentations by CDC staff will be transparent \nand evident to minimize the risk of, or the appearance of, undue influence that would \nPage 7 of 7 \n compromise the independence of the WG .  The DFO , and WGL of Influenza Immunization  WG, \nin consultation with the Chair of the Influenza Immunization  WG, will monitor the interaction \nbetween the WG  and the agency staff  to ensure that the WG  activities and work products are \nappropriate and that there is not undue influence by the CDC or by any special interest group on \nthe activities  or work products of the WG .  \n7. Timelines:  ACIP WGs are established when needed and terminated once the activities and work \nproducts stated in the terms of reference have been completed  and the WG ’s charge has been \nfulfilled .  \n8. Workgroup Meeting Summaries:  Meeting minutes will be created to capture the information \ngathered during each Influenza Immunization  WG meeting and teleconference.   \n9. Workgroup findings : The Influenza Immunization  WG will present findings (briefing \ndocuments, background materials, and presentations) to ACIP parent committee  for \nconsideration and deliberation in a public meeting.  Final versions of all slides presented at the ACIP  parent committee meeting will be posted on the ACIP website following the meeting and \nincluded in the committee’s official records.   \n10. Workgroup Record Keeping: All CDC FACA committees, subcommittees, and WGs are subject \nto the Federal Records Act.  All records will be uploaded to  the Federal Advisory Committee \nManagement Portal.  The summary report and other WG documents will become part of the ACIP’s official records as required by GENERAL RECORDS SCHEDULE 6.2: Federal Advisory Committee Records.  \nRECORDKEEPING and REPORTING  \n \nThe WG  Chair and /or WG L will present findings/outcomes/observations to the ACIP  parent \ncommittee  for discussion, deliberations, further development of recommendations, and vote in an \nopen public forum .  Approved ACIP recommendations adopted by the CDC Director wil l be \nposted on CDC’s ACIP website and also published in the Morbidity and Mortality Weekly Report (MMWR).  In addition, approved ACIP recommendations will be included in the ACIP meeting minutes  and annual report.", "summary": "Page 1 of 7   Advisory Committee on Immunization Practices  (ACIP)   Centers for Disease Control and Prevention (CDC)   Influenza  Immunization Workgroup    Terms of R eference   DRAFT: December 18 , 2025    PURPOSE    This document defines the activities, membership, and administrative requirements associated with the establishment of a n Influenza  Immunization Workgroup  under the Advisory  Committee on Immunization Practices, Centers for Disease Control and Prevention (ACIP, CDC).   ACIP…", "source_url": "https://www.cdc.gov/acip/our-work/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/influenza-tor-508.pdf", "case": "acip", "sub_case": "other", "tags": ["acip", "cdc", "vaccines", "other"], "page_count": 7}
{"title": "map wg tor 508", "content": "Page 1 of 3 \n Advisory Committee on Immunization Practices , \nCenters for Disease Control and Prevention (ACIP, CDC)  \nMeeting Administration  and Planning  Workg roup  \nTerms of Reference  \nUPDATED:  January 21, 2026  \n \n \nPURPOSE  \n \nThis document defines the activities, membership, and administrative requirements associated \nwith the establishment of a Meeting Administration and Planning Workgroup (WG)  under \nthe Advisory Committee on Immunization Practices, Centers for Disease Control and Prevention \n(ACIP, CDC).   ACIP utilizes subgroups of the Committee, known as WGs, to develop options \nfor presentation to the full ACIP  parent committee  during its public meetings to facilitate \ndiscussion, deliberation , and development of recommendations.  ACIP WGs are intended to \naugment the effectiveness of ACIP.  The direction, focus, and pace of both ACIP and the \nindividual WGs are guided by CDC and HHS policies and priorities, a s well as the need for \nexpert input to inform development of  CDC  immunization policy.   \n \n \nDESCRI PTION of WG ACTIVITIES   \nThe Meeting Administration and Planning W G will support the Designated Federal Officer \n(DFO) with ACIP meeting preparation and planning.  The WG’s activities may involve input  \nfrom other Federal and private partners:    \n• Provide input to  the DFO regarding  the d evelop ment  and coordination of  ACIP meeting \nagendas , schedules, and critical  materials to prepare members for the meetings .   \n• Provide suggestions to the DFO on needed s upport  for orderly discussion s and time \nmanagement  for ACIP meetings . \n \nThe WG will provide information  and suggestions  to the D FO for consideration.  The D FO \nwelcomes this input, together with input from other relevant stakeholders and sources, and \ndetermines its application as appropriate .  For example, t he DF O will consider several  factors \nincluding operational/logistical (data availability, time needed for analyses, FDA vaccine \nlicensing timing, vaccine safety and efficacy data, etc.) and priorities (current administration, \nHHS, CDC Director, and CDC programs) that inform  agenda topic selection for an ACIP \nmeeting.  \n \nMEMBERSHIP  \n \nThe Meeting Administration and Planning W G is chaired by a member of the ACIP committee . \nThe ACIP DFO or a designee from the ACIP Secretariat will serve as the WG Lead (WGL) .  The \nWG Chair , in consultation with both the WGL and the ACIP  DFO,  determines  the WG’s \nmembership , work priorities , and deliverables .  Other federal staff (e.g., HHS leadership) and \nPage 2 of 3 \n members of liaison representatives may be invited to join WG meetings for expertise as needed \nbut will not serve as WG members or  participate in any deliberations or WG discussions . \n \nWG Membership : The Meeting Administration and Planning WG is comp osed of  a WG Chair \nand up  to 5 additional ACIP voting members  given their professional, scientific, and technical  \nexpertise ; and vested interest in ensuring the success of the ACIP meetings.   They are experts \nwho are regarded as an authority or a practitioner of unique competence and skill by other \npersons in their profession or occupation.  Upon request, HHS federal agencies named in the \nACIP charter may also appoint members to serve on WGs.   The ACIP Chair may recommend  \nand DFO will select the WG members.   \n \nMEETINGS, ADMINISTRATION, and TIMELINES  \n1. Administrative Oversight : The  WGL will work with the WG Chair to arrange meetings, \ndocument meeting proceedings , and may provide presentations about the WG activities and \nfindings to the ACIP .   \n \n2. Meeting frequency  and location : The  Meeting Administration and Planning WG will meet  on an \nas needed basis as determined by the WG Chair , WGL, and DFO .  All Meeting Administration \nand Planning WG meetings are convened virtual ly via teleconference.  \n \n3. Meeting structure : In addition to the WGL, at least two ACIP parent committee members (one of \nwhom serves as  the Meeting Administration and Planning WG Chair)  must be present at each \nmeeting for a quorum .  An agenda, relevant publications, and background documents will be \ncirculated as read ahead mat erial prior to each meeting.  \n \n4. Conflicts of Interest : N/A.  \n \n5. Confidentiality : The discussions of the Meeting Administration and Planning WG may include \ninformation that is unpublished, protected, privileged, or confidential .  Discussions within the \nWG will be kept confidential.   Information of this nature must not be disseminated, distributed, \nor copied to persons not authorized to receive such information.   When these types of \ninformation are distributed, the person/s presenting will identify the information as such, so all \nmembers are duly informed; and written materials shall be clearly marked as such.   Unlike ACIP \nparent committee meetings , which are open to the public, Meeting Administration and Planning \nWG teleconferences are not subject to the open meeting requirements  of the Federal Advisory \nCommittee Act or the GSA Final Rule ; data presented during these meetings/teleconferences are \noften proprietary and should not be distributed to people other than approved WG members.   \n \n6. CDC Staff Involvement : The CDC staff engaged in the ACIP M eeting Administration and \nPlanning WG include the ACIP DFO and ACIP Secretariat staff .  Consultation or information al \npresentations by CDC staff may be requested by the WG .  CDC staff do not serve as members of \nthe Meeting Administration and Planning  WG but may be asked to provide administrative \nsupport and technical expertise to ACIP WGs, bringing subject matter expertise and current \nprofessional focus in areas relevant to the goa ls of the WG.  Consultation or informational \npresentations by CDC staff will be transparent and evident to minimize  the risk of, or the \nappearance of, undue influence that would compromise the independence of the WG.  The ACIP, \nPage 3 of 3 \n CDC DFO and WGL of the Meeting Administration and Planning WG, in consultation with the \nChair of the Meeting Administration and Planning  WG, will monitor the interaction between the \nWG and the agency staff to ensure that the WG activities and work products are appropriate and \nthat there is not undue influence by the CDC or by any special interest group on the activities or \nwork products of  the WG.  \n \n7. Subject content : Findings  and opinions of the Meeting Administration and Planning WG \nmembers may be discussed at ACIP meetings.  Where applicable, t he Meeting Administration \nand Planning WG’s findings will be presented to the ACIP  parent committee  for consideration \nfor action (discussion, deliberation and decision , and recommendations ).   \n \n8. WG Meeting Summaries : Meeting  minutes will be created to capture the information gathered \nduring each Meeting Administration and Planning WG meeting and teleconference.   \n \n9. WG finding s: The Meeting Administration and Planning WG will present any products to the \nACIP  DFO and at the ACIP meeting, as applicable .  Final versions of any products that may be \nproduced and  presented at the ACIP parent committee meeting will be included in the \ncommittee’s official records.   \n \n10. WG Record Keeping : All CDC FACA committees, subcommittees, and WGs are subject to the \nFederal Records Act.  All records will be uploaded in the Federal Advisory Committee \nManagement Portal.  The summary report of WG meeting activities and other WG documents \nwill become part of the ACIP’s official records as required by GENERAL RECORDS \nSCHEDULE 6.2: Federal Advisory Committee Records . \n \nRECORDKEEPING and REPORTING  \n \nThe WG will share approved products with the ACIP DFO and at ACIP meeting , if applicable.", "summary": "Page 1 of 3   Advisory Committee on Immunization Practices ,  Centers for Disease Control and Prevention (ACIP, CDC)   Meeting Administration  and Planning  Workg roup   Terms of Reference   UPDATED:  January 21, 2026       PURPOSE     This document defines the activities, membership, and administrative requirements associated  with the establishment of a Meeting Administration and Planning Workgroup (WG)  under  the Advisory Committee on Immunization Practices, Centers for Disease Control and…", "source_url": "https://www.cdc.gov/acip/our-work/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/map-wg-tor-508.pdf", "case": "acip", "sub_case": "other", "tags": ["acip", "cdc", "vaccines", "other"], "page_count": 3}
{"title": "rmr wg tor 508", "content": "Page 1 of 4 \n Advisory Committee on Immunization Practices , \nCenters for Disease Control and Prevention (ACIP, CDC)  \nRecommendation Methodology Review Workgroup   \nTerms of Reference  \nUPDATED:  January  21, 2026 \n \nPURPOSE  \n \nThis document defines the activities, membership, and administrative requirements associated \nwith the establishment of a Recommendation Methodology Review Workgroup  under the \nAdvisory Committee on Immunization Practices, Centers for Disease Control and Prevention \n(ACIP, CDC).   ACIP utilizes subgroups of the Committee, known as Workgroups (WGs), to \ndevelop options for presentation to the full ACIP  parent committee  during its public meetings to \nfacilitate discussion, deliberation , and development of recommendations.  ACIP WGs are \nintended to augment the effectiveness of ACIP.  The direction, focus, and pace of both ACIP and \nthe individual WGs are guided by CDC and HHS policies and priorities, a s well as the need for \nexpert input to inform development of  CDC  immunization policy.   \n \n \nBACKGROUND  \n \nACIP and its WGs  address a wide range of issues related to U.S. immunization policies and \npractices.  Their work has primarily focused on three areas:  (1) recommendations for specific \npopulations regarding the use or non -use of immunization products for particular infections or \ndiseases (target indications); (2) recommendations on the optimal timing, dosing, and intervals of \nimmunization products; and (3 ) recommendations on the coordinated use of multiple licensed \nimmunization products across different target indications within the overall immunization \nschedule.  \n \nACIP provides evidence -based recommendations to the CDC Director on immunization policy.  \nA critical initial step in ACIP WG activities and committee deliberations is the prospective \nformulation of clear, well -defined policy questions and related hypotheses.  Doing so requires \nthe use of an optimal and consistent framework to guide evidence review and decision -making.   \n \n \nTOPICS UNDER DISCUSSION   \nThe WG will discuss  topics that will address  historical use and potential revisions to  ACIP \nframeworks ; policy questions and evidence assessment  formulation ; vaccine timing, dosing and \nscheduling considerations; implementation , economic , and resource considerations; uncertainty, \nassumptions, and evidence gaps; and transparency and documentation.  \n     \nDESCRI PTION of WORKGROUP  ACTIVITIES   \nThe following activities provide a framework for the Recommendation Methodology Review  \nWorkgroup multi -year efforts , which may involve input  from other Federal and private partners:    \nPage 2 of 4 \n • Assess the manner and the consistency of the use of existing frameworks that have been \nadopted and used by ACIP  and its workgroups  to facilitate evidence assessment, \ndecision -making and recommendations  – including Grading of Recommendations, \nAssessment, Development and Evaluation ( GRADE ); and Evidence to Recommend ations  \n(EtR).  \n• Define Scope and Criteria – Establish decision criteria for evaluating processes for \ndeveloping discussion and presenting framing models that capture considerations related \nto benefits, risks, uncertainties and ethics (to include rigor, transparency, usability, \nadaptability, relevance, scalability, resource needs).  \n• Identify Relevant Models  – Compile a comprehensive inventory of nationally and \ninternationally used evidence frameworks , as well as models and frameworks to assess  \nbenefits,  effectiveness, risk, safety , and uncertainty . This will include review of other  \nframework s used in public and private organizations responsible for high consequence \ndecision making (e.g., impacting lives and health of people)  \n• Conduct Systematic Evidence Scan  – Review literature, guidelines, and organizational \nmethodologies to gather detailed information on each identified model.  \n• Assess Each Model Components  – Evaluate (i) structure ; (ii) the way benefits, risks and \nuncertainties are analyzed and presented; (iii) evidence appraisal methods ; (iv)  discussion \nand decision framing;  (v) transparency ; (vi)  reproducibility ; (vii)  stakeholder -engagement \nmechanisms, and other considerations.  \n• Engage Subject Matter Experts  – Consult with internal and external experts for input on  \nfindings and capture practical insights on model implementation.  \n• Identify Strengths, Limitations , and Gaps  – Summarize benefits, constraints, and \ncontextual considerations for each model, including resource implications.  \n• Determine Ideal or Hybrid Model  – Present the model (or combination of components \nfrom multiple models) that best aligns with ACIP needs and broader system goals.  \n• Develop Summary Report  – Prepare a concise report outlining methods, findings, \ncomparisons, and the final options . \n• Present Findings  – Deliver a briefing with options/findings , rationale, and proposed next \nsteps for adoption or further refinement  at an upcoming ACIP meeting . \n \nMEMBERSHIP  \n \nThe Recommendation Methodology Review Workgroup is chaired by one of the ACIP members \nappointed to serve as a Special Government Employee.   The ACIP DFO or a designee will serve \nas the Workgroup Lead (WGL) .  The WGL and the ACIP DFO , in consultation with WG Chair , \ndetermine  the WG’s membership , work priorities , and deliverables  for presentation to the full \ncommittee .  Other federal staff (e.g., HHS leadership) and members of liaison representatives , \nand additional external subject matter experts may be invited to join workgroup meetings on an \nad hoc basis, to provide expertise as needed but will not participate as members of the \nworkgroup  or participate  in any deliberations or WG discussions . \n \nWorkgroup Membership : The Recommendation Methodology Review Workgroup  is comp osed \nof a WG Chair and up  to 5 additional ACIP voting members  given their professional, scientific, \nand technical  expertise ; and vested interest in ensuring the success of the ACIP meetings.   They \nare experts who are regarded as an authority or a practitioner of unique competence and skill by \nPage 3 of 4 \n other persons in their profession or occupation.  Upon request, HHS federal agencies named in \nthe ACIP charter may also appoint members to serve on WGs.   \n \nMEETINGS, ADMINISTRATION, and TIMELINES  \n1. Administrative Oversight : The  WGL will work with the WG Chair to arrange meetings, \ndocument meeting proceedings , and may provide presentations about the WG activities and \nfindings to the ACIP .   \n \n2. Meeting frequency  and location : The  Recommendation Methodology Review Workgroup  will \nmeet  on an as needed basis as determined by the WG Chair , WGL, and ACIP DFO . All \nRecommendation Methodology Review Workgroup  meetings are convened virtual ly via \nteleconference.  \n \n3. Meeting structure : In addition to the WGL, at least two ACIP parent committee members (one of \nwhom serves as  the Recommendation Methodology Review Workgroup  Chair)  must be present \nat each meeting for a quorum .  An agenda, relevant publications, and background documents  will \nbe circulated as read ahead mat erial prior to each meeting.  \n \n4. Conflicts of Interest : N/A.  \n \n5. Confidentiality : The discussions of the Recommendation Methodology Review Workgroup  may \ninclude information that is unpublished, protected, privileged, or confidential .  Discussions \nwithin the workgroup will be kept confidential.   Information of this nature must not be \ndisseminated, distributed, or copied to persons not authorized to receive such information.   When \nthese types of information are distributed, the person/s presenting will identify the information as \nsuch, so all members are duly informed; and written materials shall be clearly marked as such.   \nUnlike ACIP parent committee meetings, which are open to the public, Recommendation \nMethodology Review Workgroup  teleconferences are not subject to the open meeting \nrequirements  of the Federal Advisory Committee Act or the GSA Final Rule ; data presented \nduring these meetings/teleconferences are often proprietary and should not be distributed to \npeople other than approved workgroup  members.   \n \n6. CDC Staff Involvement :  The CDC staff engaged in the ACIP Recommendation Methodology \nReview Workgroup  include the ACIP DFO and designee .  Consultation or information al \npresentations by CDC staff may be requested by the WG .  CDC staff do not serve as members of \nthe Recommendation Methodology Review WG but may be asked to provide administrative \nsupport and technical expertise to ACIP WGs, bringing subject matter expertise and current \nprofessional focus in areas relevant to the goa ls of the WG.   Consultation or informational \npresentations by CDC staff will be transparent and evident to minimize the risk of, or the \nappearance of, undue influence that would compromise the independence of the WG.  The \nACIPDFO and WGL of the Recommen dation Methodology Review WG, in consultation with \nthe WG Chair, will monitor the interaction between the WG and the agency staff to ensure that \nthe WG activities and work products are appropriate and that there is not undue influence by the \nCDC or by any special interest group on the activities or work products of the WG.  \n \nPage 4 of 4 \n 7. Timelines : ACIP WGs are established when needed and  terminated once the activities and work \nproducts stated in the terms of reference have been completed  and the  WG’s charge has been \nfulfilled .  \n \n8. Subject content : Findings  and opinions of the Recommendation Methodology Review \nWorkgroup  members will be discussed at ACIP meetings.  Where applicable, t he \nRecommendation Methodology Review Workgroup’s  findings will be presented to the ACIP  \nparent committee  for consideration for action (discussion, deliberation and decision , and \nformulations of recommendations ).   \n \n9. Workgroup Meeting Summaries : Meeting  minutes will be created to capture the information \ngathered during each Recommendation Methodology Review Workgroup  meeting and \nteleconference.   \n \n10. Workgroup finding s: The Recommendation Methodology Review Workgroup  will present \nbriefing documents, background materials, presentations to the ACIP parent committee for \nconsideration and deliberation in a public meeting.  Final versions of all products /slides \npresented at the ACIP parent committee meeting will be included in the committee’s official \nrecords  and uploaded into the Federal Advisory Committee Management Portal . \n \n11. Workgroup Record Keeping : All CDC FACA committees, subcommittees, and WGs are subject \nto the Federal Records Act.  All records will be uploaded in the Federal Advisory Committee \nManagement Portal.  The summary report of WG meeting activities and other WG documents \nwill become part of the ACIP’s official records as required by GENERAL RECORDS \nSCHEDULE 6.2: Federal Advisory Committee Records . \n \nRECORDKEEPING and REPORTING  \n \nThe Workgroup will present findings/outcomes/observations to the ACIP parent committee for \ndiscussion, deliberation, and potential adoption  in an open public forum.", "summary": "Page 1 of 4   Advisory Committee on Immunization Practices ,  Centers for Disease Control and Prevention (ACIP, CDC)   Recommendation Methodology Review Workgroup    Terms of Reference   UPDATED:  January  21, 2026    PURPOSE     This document defines the activities, membership, and administrative requirements associated  with the establishment of a Recommendation Methodology Review Workgroup  under the  Advisory Committee on Immunization Practices, Centers for Disease Control and Prevention …", "source_url": "https://www.cdc.gov/acip/our-work/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/rmr-wg-tor-508.pdf", "case": "acip", "sub_case": "other", "tags": ["acip", "cdc", "vaccines", "other"], "page_count": 4}
{"title": "rsv tor 508", "content": "Advisory Committee on Immunization Practices  (ACIP)  \nCenters for Disease Control and Prevention (CDC)  \nRespiratory Syncytial Virus (R SV) Immunization Workgroup, Materna l, Infant, Adult  \nTerms of Reference  \nUPDATED: December  18, 2025 \n \n \nPURPOSE  \nThis document defines the activities, membership, and administrative requirements associated \nwith the establishment of a  Respirat ory Sync ytial Virus  (RSV)  Immunization Workgroup for \npatients of all ages under the Advisory Committee on Immunization Practices, Centers for \nDisease Control and Prevention (ACIP, CDC).  ACIP utilizes subgroups of the Committee, known \nas Workgroups (WGs), to review relevant published and unpublished data, and clinical and \nscientific knowledge, and develop options for presentation to the full ACIP parent committee during its public meetings  to facilitate discussion, deliberation and development of \nrecommendations. ACIP WGs are intend ed to enhance the effectiveness of ACIP.  The direction, \nfocus and pace of both ACIP and the individual WG’s are guided by CDC and HHS priorities, and by the need for expert advice to inform development of immunization policy. ACIP WGs \nserve a key scientific role in support of immunization recommendations.  \n The RSV Immunization WG has been established to review data as well as scientific and clinical knowledge on RSV vaccine products and monoclonal antibodies currently in use or under \nconsideration for the prevention of severe RSV infection in both the infant  and at -risk adult \npopulation. These findings will be presented to the full ACIP  parent committee  in a public forum \nand will be considered in the formulation of recommendations regarding the use of these \nproducts to the Director of the CDC. \n  BACKGROUND  \nRSV is a viral illness primarily affecting infants , but older children and adults with certain co -\nmorbidities  or of older age  are also at risk of serious disease. Infants who get RSV almost always \nhave symptomatic disease. While the majority of RSV infections are mild —70% -- and localized \nto the upper airway , RSV can also cause severe illness such as bronchiolitis (inflammation of the \nsmall airways in the lungs) and pneumonia (infection of the lungs).  Before the introduction of universal RSV immunization recommendations for infants in 2023, RSV was the leading cause of hospitalization among U.S. infants (aged <12 months): an estimated one ( 1)%–three ( 3)% of \ninfants w ere hospitalized for RSV each year , accounting for the largest non- birth hospital ization \nhealth care expenditures in the US for children under five (5 ).  Adults, unlike infants, may not \nalways show symptoms after infection with RSV . However, some  adults , including those with \ncertain medical conditions, especially those associated with respiratory compromise and immune compromise, are at risk of severe disease including pneumonia, exacerbation of underlying chronic conditions such as heart failure and chro nic obstructive pulmonary disease (COPD), and \ndeath. Older adults are also at increased risk of severe RSV disease and at increased risk of \ndeclining functional status after RSV infection.  \n \nCDC recommends several U.S. Food and Drug Administration (FDA) -approved products to \nprovide active or passive immunity to the at -risk populations . One such product is a recombinant \nprotein subunit vaccine with ASO1E adjuvant approved by FDA on May 3, 2023 for adults 60 \nyears of age and older  for the prevention of lower respiratory tract disease (LRTD) caused by \nRSV. In July 2025 FDA announced the agency  also accepted an application to review use of this \nsame product for  adults  aged  18-49 years at increased risk of LRTD caused by RSV .  \n A second product is  a bivalent recombinant protein subunit vaccine with no adjuvant, approved \nby FDA  on: \n \n• May 31,2023 for adults 60 years of age and older  for the prevention of LRTD ; \n \n• August 21, 2023 for maternal vaccination at 32- 36 weeks ’ gestation  for prevention of \nLRTD in infants through 6 months of age ; and approved  \n \n• October 22, 2024 for adults ages 18 -59 with risk factors  for the prevention of LRTD .   \n \nBoth protein subunit vaccines target sites on the pre- fusion F (preF) protein on the surface of the \nRSV virus .  \n A third product  is an mRNA -based vaccine approved  by FDA  on May 31, 2024,  fo r adults  60 \nyears of age and older  for the prevention of LRTD caused by RSV , and approved by FDA  on \nJune 12, 2025 for those age d 18- 59 years at increased risk of LRTD caused by RSV .  This \nproduct also targets the preF protein.  \n For the indication of protection of adults, two of the products have shown significant efficacy in \nrandomized clinical trials  against preventing lower respiratory tract illness (LRTI) and \neffectiveness in post -licensure observational studies  against hospitalization.  For the indication of \nmaternal use of RSV vaccine to protect infants after birth, randomized clinical trials for one of \nthese products have also demonstrated efficacy  and a postmarketing real world effectiveness \nstudy also showed the vaccine to be effective . \n Two of the available products  have been associated with rare but significant adverse reactions in \nolder adults , notably Guilla in-Barrè Syndrome . There was also an imbalance of atrial fibrillation \nin the clinical trials for the use of these vaccines in adults 60 and older, but no signal has emerged in post -marketing studies to date, though safety surveillance is ongoing. No cases of \nGuillain -Barrè Syndrome have been reported in pregnant women after RSV vaccination.  \n One product has  also shown significant efficacy in preventing L RTI in randomized clinical trials . \nBecause approval of this product was more recent than for  other available products  and uptake of \nthis product has been lower, there are not yet post -licensure observational studies of vaccine \neffectiveness available.   \n In addition to vaccines there are three  monoclonal antibody products now available for newborn \ninfants  and some older children, each providing long- term passive immunity (One product was \napproved by FDA  in 2023 for use in infants born during or entering their first RSV season and \nchildren up to 24 months of age who remain vulnerable to severe RSV disease through their \nsecond RSV season . A second product clesrovimab was approved by FDA in June 2025 for \ninfants born during or entering their first RSV season. CDC recommends e ither product  for \ninfants younger than 8 months born during or entering their first RSV season; for children ages 8 through 19 months who are at  increased risk of severe RSV disease and entering their second \nRSV season, only one is recommended.  A third product, was  first approved in the United States \non June 19, 1998 and will be available until the end of December, 2025.  Two of the products  \nhave  both shown significant efficacy in randomized clinical trials against preventing RSV -\nassociated medically attended lower respiratory tract illness (RSV MA -LRTI)  and RSV MA -\nLRTI with hospitalization. P ost-licensure observational studies  have demonstrated that one \nproduct  is effective in preventing RSV -associated  hospitalization . \n The WG will engage external subject matter experts, as needed, to support presentations to the WG members and development of materials for presentation  to the parent committee for its \ndeliberations.  \n TOPICS FOR DISCUSSION BY THE WORKGROUP  \nThe topics for discussion by the RSV immunization workgroup can be most efficiently described \nby breaking them into two groups: 1)  adult populations (18 -49 with risk factors, 50 and older \nwith risk factors, and those 75 and above) ; and 2) the maternal -infant group  (for which there is \ncurrently a recommendation for all newborns), as well as use of a monoclonal antibody product in the second RSV season for  young children susceptible to serious RSV disease, including \ngroups such as all American Indian /Alaska Native infants.  The WG will work on questions and \ntopics described below and prepare deliverables for the ACIP parent committee to consider.  \n Adults : \nAges 18- 49 years.  The CDC is being asked to consider a recommendation for vaccination of \npersons in this age cohort with ‘risk factors’ making them susceptible to severe RSV infection.  This raises several questions for the WG , for example:  \n• What is the scope of the problem?  How many patients in this cohort are admitted to the \nhospital annually for RSV LRTI.  What are the outcomes data?  What is the total number \nof hospitalizations for LRTI of all causes in this group?  \n• What are the specific risk factors that have been identified as being significant?  \n• How are these risk -factors measured for severity?  \n• What are the critical values, (i.e. FEV1 in the case of obstructive airway disease, cardiac \noutput for those with congestive heart failure, A1C for diabetics, Creatinine levels for \nchronic renal failure patients , psychiatric assessments for patients with psychoses, etc.).  \n• What congenital or other anatomic abnormalities are of concern ? \n• What living situations , in addition to a nursing home environment , are considered to be \nhigh risk?  This information is essential for both patients a nd for the physicians caring for \nthem responsible for providing adequate education for informed consent  (noting that \ninformed consent is a matter under state law).  \n• Will boosters be necessary, and if so, how often?  \n• What are the results of o ngoing monitoring of post -licensure safety and adverse events ?  \n \nAge 50 and older with risk factors : \n• What is the scope of the problem?  \n• What are the defined risk  factors, how they are measured, and the critical values?  \n• Will boosters be needed?  The duration of immunity in this cohort is currently unknown. \n \nAge 75 and older : \n• Currently this is a universal recommendation.  The WG should provide updates on \nhospitalization rates of those vaccinated and unvaccinated, outcomes, and deaths attributed to RSV infection.  How many admissions for LRTI for any etiology are there in this cohort?  \n• The WG should provide updates  on the incidence of serious adverse events for all who \nhave been vaccinated, broken down by specific vaccine.  This cohort is particularly \nsusceptible.  \n \nMaternal -Infant and young children with risk factors : \n• What is the uptake of the maternal vaccine and how does it compare with administration \nof monoclonal antibodies to newborns?  \n• The WG should provide updates on rates of RSV -associated hospitalization in infants \nwho do not receive protection from either maternal vaccination or a monoclonal antibody, \nin infants born to mothers that received maternal vaccination, and in infants that have received monoclona l antibodies only.    \n• What is the number needed to treat to prevent a hospital admission, an ICU admission, or death?  How does that compare with the number needed to vaccinate to see a significant adverse event for each product?  \n• The WG should provide a  thorough review of the data presented at the last ACIP meeting \nin June 2025 regarding the safety of relevant RS V products .  This would include the \nstudy design, the original description of the study groups. and a reanalysis of the safety data using more sophisticated methodologies.   \n• The WG should review all raw data on the RCTs including  data from  the ongoing trials of \nRSV products.  \n• The WG should address a ny significant aberration or discrepancy between what was \npresented in June and what is found on re -analysis that may  trigger  a review of the  ACIP  \nrecommendation regarding other RSV products ?What  are the results of o n-going review s \nof post -marketing surveillance  of the immunization products?  \n  MEMBERSHIP  AND LEADERSHIP   \n  Workgroup Leadership:  The RSV Immunization WG is chaired by one of the ACIP, CDC parent \ncommittee members. The Workgroup Lead (WGL) is a federal employee, identified by the \nImmediate Office of the Director in consultation with the appropriate CDC program. The WG Chair, in consultation with the WGL, and ACIP CDC Designated F ederal O fficial (DFO), \ndetermines the WG’s membership and work priorities and deliverables to the full committee.   The DFO may further assign  some of the  DFO -related roles and responsibilities , as \nappropriate, to the WGL.   \n  \nWorkgroup Membership:  The RSV Immunization WG is composed of experts who are appointed \nbased on their professional, scientific, technical, or other expertise.  They are experts who are \nregarded as an authority or a practitioner of unique competence and skill by other persons i n their \nprofession, or occupation. Upon request, HHS federal agencies named in the ACIP charter may \nalso appoint members to serve on WGs. The RSV Immunization WG will be composed of members from a variety of disciplines. The WG will en gage with the following disciplines on \nWG activities:   \n  \n• Public health science and practice;    \n• Public health policy development, analysis, and implementation, including development and execution of immunization programs for children and adults;   \n• Clinical and medical practice, and patient- care experience;    \n• Epidemiology;    \n• Molecular biology;    \n• Immunology;    \n• Virology;    \n• Diagnostics and correlates of protection;   \n• Drug and vaccine safety;    \n• Bioethics; and    \n• Consumer perspectives and/or social and community aspects of immunization programs   \n  Due to the complexity and variability of the information to be gathered, additional external subject matter experts may also be invited to provide data and presentations to the WG and answer questions during RSV Immunization WG meetings on an a d-hoc basis. Such additional \nexternal subject matter experts will not be members of the WG and will not participate in any \ndeliberations or WG discussions.  \n  \n MEETINGS, ADMINISTRATION, and TIMELINES   \n  \n1. Administrative Oversight: The  WGL will work with the WG Chair to arrange meetings, \ndocument meeting proceedings, and report to the ACIP on the RSV  Immunization WG’s \nactivities and findings.     \n2. Meeting frequency and location : The  RSV Immunization WG will meet on an as needed \nbasis as determined by the WG Chair and WGL. All RSV  Immunization WG meetings \nare convened virtually via teleconference.   \n3. Meeting structure : In addition to the WGL, at least two ACIP parent  committee members \n(one of whom serves as the RSV  Immunization WG Chair) must be present at each \nmeeting for a quorum.  An agenda, relevant publications, and background documents will \nbe circulated as read -ahead material before each meeting.    \n4. Conflicts of Interest : WG  members will complete an ACIP WG Agreement and Conflict \nof Interest Certification process before participation on the WG.   The WGL  will screen \nfor conflict -of-interest  declarations and share any conflicts that need to be elevated to the \nDFO/ACIP Secretariat .  The ACIP Secretariat and DFO , in collaboration with the WGL  \nwill work with Ethics office within the Office of Strategy Business Initiatives (OSBI) and \nthe Office of General Counsel (OGC), as needed, to resolve any conflicts th at the WGL \nidentifie d.  WG members will consent to abide by guiding principles and disclose \ninterests (e.g., employment, special interests, grants, or contracts) that a reasonable \nperson could view as conflicts or potential conflicts of interest with their RSV  \nImmunization WG participation.   Members will also disclose any potential conflicts of \ninterest before each meeting.   If an  RSV Immunization WG member indicates a potential \nor actual conflict of interest to the WGL, the WGL or a delegate will  forward  any \nconflicts to the DFO to determine whether the individual must recuse themselves from participating in WG discussions that implicate such a conflict -of-interest concern.   If \nneeded, the  DFO will engage OSBI and OGC to assist with making COI determination.   \n5. Confidentiality : The discussions by the RSV Immunization WG may include information \nthat is unpublished, protected, privileged, or confidential. WG deliberations, including policy options under consideration by the WG, are also considered confidential.   Information of this nature must not b e disseminated, distributed, or copied \nto persons not authorized to receive such information.  When these types of information \nare distributed, the person  presenting will identify the information as such, so all \nmembers a re duly informed; and written materials shall be clearly marked as \nsuch.  Unlike ACIP  parent committee  meetings, which are open to the public, RSV  \nImmunization WG teleconferences are not subject to the open meeting requirements of the Federal Advisory Committee Act or the GSA Final Rule; data presented during these meetings/teleconferences are often proprietary and should not be distributed to peopl e \nother than approved RSV  Immunization WG members.     \n6. CDC Staff Involvement: CDC staff do not serve as members of the RSV Immunization \nWG but may provide administrative support and technical expertise to ACIP WGs, as appropriate, bringing subject matter expertise and current professional focus in areas \nrelevant to the goals of the RSV Immunization WG.  Consultation or informational \npresentations by CDC staff will be transparent and evident to minimize the risk of, or the \nappearance of, undue influence that would compromise the independence of the \nWG.   The DFO a nd WGL of the RSV Immunization WG, in consultation with the Chair \nof the RSV Immunization WG, will monitor the interaction between the WG and the agency staff to ensure that the WG activities and work products are appropriate and that there is no undue influence by the CDC or by any special interest group on the activities or work products of the WG.   \n7. Timelines : ACIP  WGs are established when needed and terminated once the activities \nand work products stated in the terms of reference have been completed and the WG’s charge has been fulfilled.    \n8. Workgroup Meeting Summaries:  Meeting minutes will be created to capture the \ninformation gathered during each RSV  Immunization WG meeting and teleconference.     \n9. Workgroup findings : The RSV Immunization WG will present findings (briefing \ndocuments, background materials, and presentations) to the ACIP  parent committee for \nconsideration and deliberation in a public meeting.  Final versions of all slides presented at the ACIP  parent committee  meeting will be posted on the ACIP website following the \nmeeting and included in the committee’s official records.     \n10. Workgroup Record Keeping: All CDC FACA committees, subcommittees, and WGs are \nsubject to the Federal Records Act.   All records will be uploaded to the Federal Advisory \nCommittee Management Portal.  The summary report  of WG meeting activities  and other \nWG documents will become part of the ACIP’s official records as required by GENERAL RECORDS SCHEDULE 6.2: Federal Advisory Committee Records .  \n  \nRECORDKEEPING and REPORTING    \nThe WG Chair and WGL will present  findings/outcomes/observations/recommendations to the \nACIP parent committee for discussion, deliberations, further development of recommendations, and vote in an open public forum. Approved ACIP recommendations adopted by the CDC Director will be posted on CDC’s ACIP website and al so published in the Morbidity and \nMortality Weekly Report (MMWR). In addition, approved ACIP recommendations will be included in the ACIP meeting minutes and annual report.", "summary": "Advisory Committee on Immunization Practices  (ACIP)   Centers for Disease Control and Prevention (CDC)   Respiratory Syncytial Virus (R SV) Immunization Workgroup, Materna l, Infant, Adult   Terms of Reference   UPDATED: December  18, 2025      PURPOSE   This document defines the activities, membership, and administrative requirements associated  with the establishment of a  Respirat ory Sync ytial Virus  (RSV)  Immunization Workgroup for  patients of all ages under the Advisory Committee on…", "source_url": "https://www.cdc.gov/acip/our-work/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/rsv-tor-508.pdf", "case": "acip", "sub_case": "other", "tags": ["acip", "cdc", "vaccines", "other"], "page_count": 7}
{"title": "ACIP Evidence to Recommendations Framework cdc", "content": "ACIP Evidence to Recommendations Framework  \n \nQuestion: Overarching policy question to be answered by the guideline panel (ACIP)  using the Evidence to Recommendations (EtR) frame work. \nThe quest ion shou ld be precise and ident ify the specific interv ention, compar ison, and outcome, as w ell as the tar get popul ation and t he setting \n(specific s ubpopul ations) in PICO format.  \nPopula tion: Target popul ation  for vaccine (e.g., a ge range, se x, immune sta tus, pregnancy )    \nIntervention: Vaccination (if appl icable, dosag e and sc hedul e)   \nCompa rison(s): No Vaccination/S tandard  of care/An existing vaccine/O ther prevention option   \nOutcome : Outcome(s) associated with vaccination  (e.g., prevention outcomes or adverse effects)  \n \n \nBackground: The addressed PICO question should be described in detail, and important background information for understanding the questio n \nand why a recommendation or decision is needed should be briefly provided.  If a recommendation is preferential or represents off-label use, \nthis should be indicated.  \nInclude sample language: Additional background information supporting the ACIP recommendations on the use of xxx vaccine can be found in \nthe relevant publication of the recommendation referenced on the ACIP website . \n \n \n WORK GROUP  JUDGMENTS  EVIDENCE  ADDITIONAL INFORMATION  PROBLEM  Is the problem of public health importance?  \n \n○ No \n○ Probably no  \n○ Probably yes  \n○ Yes \n \n○ Varies  \n○ Don't know  Provide available  scientific evidence on \nburden of  disease, preferably within the  \ntarget population for the  \nrecommendation.  \n \nIf no published evidence is available,  \nprovide expert judgment on the  public \nhealth priority  considerations.  Identify any additional public health  \npriority  considerations, including \nconsideration of disparities.  \n \n  \nWORK GROUP JUDGMENTS  EVIDENCE  ADDITIONAL INFORMATION  BENEFITS & HARMS  How substantial are the desirable \nanticipated effects?  \n○Minimal\n○S\nmall\n○M\noderate\n○L\narge\n○Va\nries\n○D\non't knowDescribe the magnitude of the  beneficial  \neffects of vaccination  on individual \n(vaccine  effectiveness, duration of \nprotection) and population  (herd \nimmunity) levels.   Take into consideration: \nIs the baseline benefit similar across \nsubgroups (by age, sex,  pregnancy or \nlactation s tatus, occupation [ i.e., healthcare \nworkers], immune s tatus, r ace, S ES, and \nother gr oups)? \nAre there indirect ef fects that should b e \nconsidered ( e.g.,  herd i mmunity)? \nHow substantial are the undesirable \nanticipated effects?  \n○Minimal\n○S\nmall\n○M\noderate\n○L\narge\n○Va\nries\n○D\non't knowAre there undesirable effects of the \nvaccine, either on the individual (e.g., \nadverse events following immunization) or population (e .g., age -shift of disease, \nserotype replacement) levels?  Take into consideration:  \nIs the baseline risk for harm similar across subgroups (see above)?  \nS\nhould there be separate recommendations \nfor subgroups based on harms?  \nDo the desirable effects outweigh the \nundesirable effects?  \n○Favors interventionl\n○F\navors comparison\n○F\navors both\n○F\navors neither\n○Va\nries\n○D\non't knowDescribe the balance of benefits of the \nvaccine with possible harms (individual and population level).  \n \n WORK GROUP JUDGMENTS  EVIDENCE  ADDITIONAL INFORMATION  \n What is the overall certainty of this \nevidence for the critical outcomes ? \n \nEffectiveness of the intervention  \n○ No  studies found  \n○ 4 (very low)  \n○ 3 (low)  \n○ 2 (moderate)  \n○ 1 (high)  \n \nSafety of the intervention  \n○ No studies found  \n○ 4 (very low)  \n○ 3 (low)  \n○ 2 (moderate)  \n○ 1 (high)  \n Please refer to GRADE evidence profiles  for \ndetailed assessment of the certainty of the \nevidence. For more information, please see the\n ACIP Handbook for Developing Evidence -\nBased Recommendations.   If GRADE was n ot used to evaluate the \ncertainty of evidence, please provide \njustification and the method and outcome of any other tools used to evaluate the body of evidence relevant to the critical outcomes.  VALUES  Does the target population feel that the \ndesirable effects are large relative to \nundesirable effects?  \n \n○ No \n○ Probably no  \n○ Probably yes  \n○ Yes \n \n○ Varies  \n○ Don't know  Provide any available evidence on target \npopulation values & preferences related to \nvaccination and comparative health benefits \nand risks. Describe the source of these estimates.  Are values and preferences for relevant \noutcomes measured?  Are the benefits, \nharms and costs of vaccination valued \ndifferently by different subgroups?  \n  If the target group doesn’t value the intervention, or attributes little value to the \nharms and benefits, consider whether potential education measures are needed.  \n   \n \n  \n WORK GROUP JUDGMENTS  EVIDENCE  ADDITIONAL INFORMATION  \nIs there important uncertainty about or \nvariability in how much people value the \nmain outcomes?  \n \n○ Important uncertainty or variability  \n○ Probably important uncertainty or variability  \n○ Probabl not important uncertainty or variability  \n○ No important uncertainty or variability  \n○ No known undesireable outcomes  \n Please provide available data used to \ndetermine the relative importance that the \ntarget population attributes to the desirable \nand the undesirable outcomes related to the \nintervention as well as the comparison.  Describe the source of variability, if any.  \n \nAre there methods for determining values \nsatisfactory for this recommendation?  \n \nIf not, systematic assessment of values and \npreferences of target group may be \nconsidered.  ACCEPTABILITY  Is the intervention acceptable to key \nstakeholders?  \n \n○ No \n○ Probably no  \n○ Probably yes  \n○ Yes \n \n○ Varies  \n○ Don't know  \n Provide assessment of whether intervention \nwould be acceptable to stakeholders \n(ethically, programmatically, financially, etc.)   RESOURCE USE  Is the intervention a reasonable and \nefficient allocation of resources?  \n \n○ No \n○ Probably no  \n○ Probably yes  \n○ Yes \n \n○ Varies  \n○ Don't know  \n Provide summary of cost -effectiveness \nanalyses (CEAs) of the vaccine in the target \npopulation. Include base case results and a \nsensitivity range. Include any other notable \nfindings, for example, specific policy -\nrelevant scenario s.  Overall findings: Summarize the findings \nfrom available CEAs, including major \ndifferences in baseline assumptions.  \n \nUncertainty: Does the analysis capture the \nfull range of uncertainty? For example, are \nthe findings from the uncertainty of \nevidence ana lysis, identified earlier in this \ndocument (the EtR Framework), \nappropriately represented in the methods of \nthe CEAs?  \n \nMultiple assessments: Are there multiple \nCEAs? If so, what are the major differences \nin methods and results?  \n \n WORK GROUP JUDGMENTS  EVIDENCE  ADDITIONAL INFORMATION  EQUITY  What would be the impact on health \nequity?  \n \n○ Reduced  \n○ Probably reduced  \n○ Probably no impact  \n○ Probably increased  \n○ Increased  \n \n○ Varies  \n○ Don't know  \n Summarize the findings from a review of the \nliterature addressing issues of health inequities or groups who may be disadvantaged.  Consider from the evidence or guideline \npanel:  \n• Are there any groups or settings that might be disadvantaged in relation to \nthe problem or options that are \nconsidered?  \n• Are there plausible reasons for \nanticipating differences in the relative effectiveness of the option for disadvantaged groups or settings? \n• Are there different baseline conditions across groups or settings that affect the \nabsolute effectiveness of the option o r \nthe importance of the problem for \ndisadvantaged groups or settings? \n• Are there important considerations \nthat should be made when implementing the intervention (option) in order to ensure that \ninequities are reduced, if possible, \nand that they are not incr eased?  FEASIBILITY  Is the intervention feasible to implement?  \n \n○ No \n○ Probably no  \n○ Probably yes  \n○ Yes \n \n○ Varies  \n○ Don't know  \n Are there any barriers to implementation?  \n Please refer to the Implementation \nConsiderations checklist. \nBalance of \nconsequences  Undesirable \nconsequences  \nclearly outweigh  \ndesirable \nconsequences  \nin most settings  Undesirable \nconsequences \nprobably outweigh  \ndesirable \nconsequences  \nin most settings  The balance \nbetween  \ndesirable and \nundesirable \nconsequences  \nis closely balanced \nor uncertain  \n Desirable \nconsequences  \nprobably outweigh  \nundesirable \nconsequences  \nin most settings  Desirable \nconsequences  \nclearly outweigh  \nundesirable \nconsequences  \nin most settings  There is \ninsufficient \nevidence to \ndetermine the \nbalance of \nconsequences  \n ○ ○ ○ ○ ○ ○ \nIs there sufficient information to move forward with a recommendation?  \nYes   ○                                              No   ○    \n \n \nPolicy options for \nACIP consideration   \nACIP does not recommend the \nintervention*   \n*Intervention may be used within \nFDA licensed indications  \n  \nACIP recommends the intervention \nfor individuals based on shared \nclinical decision -making    \nACIP recommends the intervention  \n ○ ○ ○ \n \nDraft \nrecommendation \n(text)  Please provide the draft recommendations proposed to ACIP.  \n \nAdditional \nconsiderations  \n(optional)  Please outline any significant additional considerations (e.g., aspects related to implementation, monitoring and \nevaluation, research priorities, etc.).  \n \n \n \nFinal deliberation and decision by the ACIP  \n \n \nFinal ACIP \nrecommendation  \n  \nACIP does not recommend the \nintervention*  \n*Intervention may be used within FDA \nlicensed indications  \n  \nACIP recommends the intervention for \nindividuals based on shared clinical \ndecision -making    \nACIP recommends the intervention  \n \n ○ ○ ○ \nAdditional ACIP \nconsiderations  \n Wording as accepted in the guide", "summary": "ACIP Evidence to Recommendations Framework     Question: Overarching policy question to be answered by the guideline panel (ACIP)  using the Evidence to Recommendations (EtR) frame work.  The quest ion shou ld be precise and ident ify the specific interv ention, compar ison, and outcome, as w ell as the tar get popul ation and t he setting  (specific s ubpopul ations) in PICO format.   Popula tion: Target popul ation  for vaccine (e.g., a ge range, se x, immune sta tus, pregnancy )    …", "source_url": "https://www.cdc.gov/acip/evidence-based-recommendations/index.html", "pdf_url": "https://www.cdc.gov/acip/downloads/ACIP-Evidence-to-Recommendations-Framework-cdc.pdf", "case": "acip", "sub_case": "recommendations", "tags": ["acip", "cdc", "vaccines", "recommendations"], "page_count": 7}
{"title": "ACIP EtR Users Guide October 1 2020", "content": "1 \n  \n  \n \n \nA\nCIP Evidence to Recommendation User’s Guide \n \nOctober 1 , 2020\n2 \n  Contents  \nIntroduction .................................................................................................................................................. 3  \nHow to Use This Guide  .................................................................................................................................. 3  \nThe EtR Framework  ................................................................................................................................... 4  \nOrganization of this Guide  ........................................................................................................................ 5  \nOverarching Framework Completion Guidance  ....................................................................................... 5  \nSpecific Criteria  ............................................................................................................................................. 6  \nDomain 1: The Problem  ............................................................................................................................ 6  \nCriterion: Public Health Priority  ............................................................................................................ 6  \nDomain 2: Benefits & Harms of the Options  ............................................................................................ 6  \nCriterion 1: Magnitude of desirable anticipated effects  ....................................................................... 6  \nCriterion 2: Magnitude of undesirable anticipated effects  .................................................................. 7  \nCriterion 3: Balance of desirable versus undesirable anticipated effects  ............................................ 8  \nCriterion 4: Certainty of evidence for outcomes  .................................................................................. 8  \nDomain 3: Values and Preferences  ........................................................................................................... 9  \nCriterion 1: Target population perception of value  .............................................................................. 9  \nCriterion 2: Uncertainty around target population perception of value  .............................................. 9  \nDomain 4: Acceptability  .......................................................................................................................... 10 \nCriterion:  Acceptability to key stakeholders  ....................................................................................... 10 \nDomain 5: Resource Use  ......................................................................................................................... 10 \nCriterion: Resource allocation  ............................................................................................................ 10 \nDomain 6: Equity  ..................................................................................................................................... 11 \nCriterion: Healt h equity  ...................................................................................................................... 11 \nDomain 7: Feasibility  ................................ ............................................................................................... 12 \nCriterion: Implementation feasibility  .................................................................................................. 12 \nConclusions and Additional Considerations ............................................................................................ 12 \nSummary of the ACIP’s deliberations and final recommendations  ........................................................ 13 \nAdditional Resources  .................................................................................................................................. 13 \nAppendix 1: ACIP Evidence to Recommendations Framework  .................................................................. 14 \nAppendix 2 When to Prepare GRADE Evidence Profile Algorithm  ............................................................. 21 \nAppendix 3 Implementation Considerations Checklist  ............................................................................... 22 \n \n3 \n Introduction  \nIn 2010, the Advisory Committee on Immunization Practice ( ACIP ) formally adopted the Grading of \nRecommendations Assessment, Development and Evaluation (GRADE) approach for assessing the \nevidence and developing evidence -based recommendations. Since then, an assessment of the certainty \nof available evidence  using GRADE ha s been an integral part of ACIP recommendation development . In \naddition to assessing the certainty of evidence, guideline panel s consider other domains when making a \nrecommendation (e.g., the balance of benefits and harms, patient’s values and preferences, etc.). This \ndocument presents the information that must be considered when making a recommendation.  Previous \ndocuments/publica tions provide information on assessing the certainty of the evidence (Ahmed 2011 ).   \n \nD\nuring the process of recommendation formulation, panels consider a range of factors in addition to the \ncertainty in the evidence.  Elucidation of these factors and the j udgments behind them facilitates \ntransparency, consistency, and communication of recommendations to healthcare providers, partner \norganizations, and the public  (Alonso -Cuello 2017a & b) .  To structure the discussion of these additional \nfactors and to make the judgments transparent, an evidence to decision -making  (EtD) framework is \nused.  \n \nThe EtD structures decision -making by:  \n• Inform ing panel members’ judgments about the pros and cons of each intervention under \nconsideration;  \n• Ensuring the important factors that determine a decision (criteria) are considered;  \n• Provid ing a concise summary of the best available evidence to inform judgements about each \ncriterion;  \n• Helping structure discussion and identify reasons for disagreements when they occur; and  \n• Making the b asis for decisions transparent to guideline users or those affected by a policy \ndecision.  \n \nThe ACIP has continued to follow and build upon the methodological advances in the GRADE approach \nand, as a result, has developed a modified Evidence to Recommendation (EtR) framework tailored to the needs of ACIP (Appendix 1). The purpose of EtR framework is to help panels making recommendations \nmove from evidence to decisions, and to provide transparency around the impact of additional factors on deliberations when considering a recommendation .   \n \nHow to Use This Guide  \nThe following supplementary information is intended to guide ACIP work groups while they complete \nthe EtR framework , as they address specific policy questions and develop  policy options for ACIP ’s \nconsideration . \n \nACIP’s EtR frameworks are prepared by ACIP work groups for presentation to ACIP.  As such, the EtR  \nframeworks represent the information reviewed and considered by the ACIP w ork group in developing \npolicy options for ACIP’s consideration.  The ACIP’s final recommendation and any additional considerations of ACIP during its deliberations  are captured  in a separate table titled ‘Final deliberation \nand decision by ACIP’ at the bottom of the EtR framework  (Appendix 1) . \n \n4 \n The ACIP’s EtR frameworks and accompanying GRADE evidence profiles are posted on the ACIP website \n(https://www.cdc.gov/vaccines/acip/recs/index.html ), and are referenced with links in  the MMWR \nPolicy Note  or Recommendations and Reports  document s, upon publication  in MMWR . \n \nThe EtR Framework  \nThe EtR  frameworks are designed to include key background information, criteria  for making a decision, \nand conclusions . \n \nThe background section of the EtR is intended to provide details of the policy question that is the topic \nof the framework.  In the EtR framew ork table, this section is opened by a statement of the policy \nquestion and the PICO (Population, Intervention, Comparator, Outcome), followed by a brief summary of information needed to understand the question and why a recommendation is needed.  Specific  \nitems that should be addressed include whether the recommendation would be for “off -label” use (i.e., \nan indication not specified in the FDA approved label) or a preferential recommendation.\n \n  \nThe second part of the framework is composed of rows delineating the factors or criteria  considered \nduring recommendation development, which are grouped into “domains.”  These questions are \nintended to frame the discussions and guide literature searches and collection of relevant data.  \n \nT\nhe following columns are included for each criterion:  \n• Judgments  that the work group  members must make in relation to each criterion are summarized in \nthe first column of the framework as checkboxes.  In most cases, it is anticipated that the framework \nwill be  developed with  judgments  for each criterion  suggested by the work group and subject \nmatter experts (SMEs) who have prepared the framework.  The judgments should be a result of the work group reaching a consensus; however, minority opinions expressed during the discussion \nshould be  captured in the “additional considerations” section (see below).\n \n• Evidence  to inform each of those judgments is presented in the  second  column of the table. \nEvidence refers to facts  used to inform the work group’s  judgments that are derived from studies \nthat used systematic and explicit methods.1  If published evidence is available, a paragraph or \nbulleted list summarizing the important considerations is sufficient, with mention of the most \ncritical references or links to more detailed summaries of the evidence such as the GRADE evidence \nprofile1. If no peer -reviewed body of evidence is available, this should be simply stated and any \nadditional information used to inform the judgment indicated.  The intent is to be  transparent about \nthe information that was used to make the judgment, not to imply the need for the development of \nevidence when it is not available.  \n• Additional information that informs or justifies each judgment may be provided in the final, right -\nhand c olumn of the table.  Additional information can include other data, assumptions, and logic \nused to make a judgment.  Work groups  may make different judgments for one or more subgroups \n(such as patients who are older or who have more severe disease) in relation to some or all of the criteria.   When relevant, they may also report additional details, such as dissenting views of work \ngroup  members or the results of voting on judgments where there was disagreement.\n   Minority \nopinions voiced during discussions should be presented to increase transparency around the \ndeliberation process.  In addition, interpretations of the evidence may be presented here.  \n \n \n1 If using GRADEpro Guideline Development Tool software ( https://gradepro.org/ ), a GRADE evidence profile can \nbe automatically inserted into the EtR framework.  \n5 \n Organization of this Guide  \nThis document provides additional information for each domain and criterion, including the criterion \nquestion as presented in the EtR framework, related questions that expand on the issues to consider for each criterion (adapted from the GRADE Handbook ), and completion guidance.  A Discussion section is \nalso included to provide further information and clarification on issues specific to each criterion/question.  This additional information is intended to assist work groups and the ACIP in providing the relevant information to populate the framework.  \n \nOverarching Framework Completion Guid ance  \nDespite availability of a framework, individuals and groups will need to continue to make judgments at several points, especially when data are minimal or absent.  One purpose of the framework is to make \nthose judgments explicit.  Therefore, when evid ence is not available, this should be stated and a \nsummary of the discussion included.  It is also anticipated that there will be differences of opinion within \nthe work group, and the framework should be used to reflect these differences, particularly with  regard \nto the final recommendation.  Since one goal of the framework is to enhance transparency and communication of deliberations, significant differences of opinion or discussion points should be captured within each domain when relevant.   \n6 \n Specific Criteria  \nDomain 1: The Problem  \nCriterion: Public Health Priority  \nCriterion question: Is the problem of public health importance?  \nRelated questions:  \n• Are the consequences of the problem serious (i.e. severe or important in terms of the potential \nbenefits or savings)?  \n• Is the problem urgent?  \n• Are a large number of people affected by the problem?  \n• Is the problem related to emerging diseases, antimicrobial resistance, or epidemic potential?  \n• Are there disadvantaged groups or populations disproportionately/differentially affected by this problem?  \n \nC\nompletion Guidance: Provide a short summary of the background and significant elements of the \nproblem, including a description of epidemiology, clinical features , and sequelae of the \ndisease/condition in terms of public health consequences.  This may be excerpted or summary information from presentations to the full ACIP.  Specific items to consider may include: \n \n• F\nrequency of the disease/condition (e.g., incidence,  prevalence, secular trends)  \n• Severity of the disease/condition (e.g., mortality, morbidity)  \n• Social impact of the disease/condition (e.g., hospitalization rate, sickness absenteeism, effects on high -risk groups and vulnerable  populations, clinical features,  perception of importance, and \nthe existence of other  preventive measures)  \n \nA\nny additional considerations regarding the public health priority may also be included.  \n \nDomain 2: Benefits & Harms of the Options  \nCriterion 1: Magnitude of desirable anticipated effects  \nCriterion question: How substantial are the desirable anticipated effects?  \nRelated question:  \n• How substantial is the anticipated effect for each main outcome for which there is a desirable effect?  \n \nC\nompletion Guidance:  Across  the critical outcomes (as specified in the PICO question and elaborated in \nthe evidence profiles), evaluate the magnitude of the anticipated effect.  The anticipated direct and indirect ( e.g.,  herd immunity) benefits of vaccination or other interventions,  should then be listed in the \nframework in terms of specified outcomes with a description of how substantial the effects are.  For effectiveness or efficacy, specific items that may be considered are immunogenicity, strain coverage, capacity to reduce the disease incidence, capacity to disrupt carriage, duration of protection, and/or serotype replacements.  \n \nT\nhe range of effectiveness/efficacy estimates should be included here, but specific information \nregarding the confidence in point estimates should be pr esented in the certainty of evidence section \n(Criterion 4) below as part of the GRADE evidence profile.  Describe any differences in \n7 \n effectiveness/efficacy estimates for special populations (e.g., immunocompromised, specific age groups, \netc.) and disadvantaged groups or settings  (i.e. baseline risk) .  Work groups should also consider the \nuncertainties (if any) related to benefit with regard to durability of effectiveness, and effect on serious health outcomes (e.g., death and hospitalization), which are not  often measured pre -licensure because \nsuch studies would require a sample size too large to be feasible.  The numbers of illnesses, hospitalizations and deaths that can be averted by use of the vaccine may be presented here but is not required.  \n \nIn\n addition, information may be included in the “additional considerations” section to highlight where \nevidence may be lacking (e.g., subgroups where additional data are needed to assess the benefits).  \n \nDiscussion  \n \nA\ndditional considerations here can include quality of life, acute and chronic pain, and functional status, \namong those who receive the vaccine and those who do not, including those who suffer the condition that could be prevented or ameliorated by vaccination.  Work groups are encouraged to perform  a \nnumber needed to vaccinate (NNV) analysis.  If a number needed to vaccinate (NNV) analysis is performed, any important uncertainty or assumptions should be included. There are no defined thresholds for an “acceptable” NNV . \n \n \nG\nuidance surrounding the use  of immunogenicity data as a surrogate for efficacy or effectiveness can be \nfound in the GRADE Handbook  (Schünemann 2013 ).  It is important to use the same language around \njudgments (e.g., “ minimal,” “small,” “moderate,” “large”) as included in the framewo rk.  The framework \nrequires that the work  group check one box  and rationale should be provided for the judgment selected \nby the work group.  However , any differences in opinions on the judgement selected should be reflected \nin the additional Information se ction to ensure transparency.  \n \nCriterion 2: Magnitude of undesirable anticipated effects  \nCriterion question: How substantial are the undesirable anticipated effects?  \nRelated question:  \n• How substantial is the anticipated effect for each main outcome for which there is an undesirable effect (taking into account the severity or importance of the adverse effects and the number of people affected)?  \n \nC\nompletion Guidance: For each of the critical outcomes (as specified in the PICO question and \nelaborated in the evidence profiles), evaluate the magnitude of the undesirable anticipated effect.  List \nthe anticipated harms of vaccination, in terms of chosen outcomes and describe how substantial those \neffects are.  Specific items to consider may include reactogenicity, adverse events, and interactions with other vaccines.  Describe any differences in harms for disadvantaged groups or settings.  As above, information may be included in the Additional Information section to highlight where evidence may be lacking.  \n \nD\niscussi on \n \nW\nhen answering this question, work groups should consider the size and strength of the pre -licensure \nsafety database to sufficiently examine safety outcomes of interest.  Groups can also discuss safety \nexperience with vaccines from the same product cla ss, and any uncertainties related to the safety of the \n8 \n product based on limitations of study design, limitations of size of safety database for rare outcomes, \nand duration of follow up.  Work groups should consider “risk of harm” (e.g., unknown long -term  effects \nof new adjuvants,  having only clinical trial data vs . long -term real- world  experience).  \n \nJust\n as for the benefits section, it is important to use the same language around judgments (e.g., \n“minimal,” “small,” “moderate,” “large”) as included in the framework.  Only one box should be \nchecked, but differences in opinions should be reflected in the Additional Information section to ensure \ntransparency.  \n \nSimilar t\no the previous criterion, work groups should consider the existing safety information for both \nthe product under consideration, as well as similar products (e.g., vaccines in the same class).   Any \nuncertainties related to safety should be clearly articulate d and discussed.  \n \nCriterion 3: Balance of desirable versus undesirable anticipated effects  \nCriterion question: Do the desirable effects outweigh the undesirable effects?  \nRelated question:  \n• What is the balance between the desirable effects relative to the undesirable effects?  \n \nCo\nmpletion Guidance: The work group should describe the deliberations on this topic, ensuring that any \nminority opinions are included.  If specific subgroups have a different benefit to harm balance than the general population, describe  those considerations here (especially if those groups are not included in \nthe recommendation on the basis of this altered balance).  \n \nDi\nscussion  \n \nWh\nen the comparator is “no vaccination,” this section is focused on comparing the balance of risks and \nbenefit s of the same  vaccine.  Comparison of the adverse events profile of this vaccine to other \nvaccine(s) available to prevent the same  disease  can be addressed in the implementation section (e.g., \ncommunication with providers and patients to ensure recipients are counseled about severity of adverse events) or in the ‘Additional Considerations ’ section.  Since  it may be difficult to compare benefits and \nrisks, as measures are inherently different, judgment must be exercised.  \n \nCriterion 4: Certainty of evidence for outcomes  \nCriterion question: What is the overall certainty  of this evidence  for the critical outcomes?  \nRelated question:  \n• What is the overall certainty of this evidence of effects, across all of the outcomes that are critical to making a decision?  \n \nCo\nmpletion Guidance: For most situations, the overall certainty of the evidence is the lowest certainty of \nthe critical outcomes. See the ACIP GRADE Handbook regarding the process of making detailed judgments about the quality of evidence or certainty in e stimates of effects and preparation of evidence \nprofiles. The GRADE evidence profiles and associated documents should be referenced here.  If there is uncertainty about whether to prepare evidence profiles, please follow the “When to GRADE” algorithm (Appe ndix 2) and consult the ACIP Secretariat.  If evidence profiles are not prepared, a rationale and \nsummary of any alternative methods should be provided.  \n  \n9 \n Discussion  \n \nI\nt is expected that the overall certainty of the evidence will be informed by the  GRADE e vidence profiles  \nused to inform Criteria 2 and 3 (benefits and harms) . If evidence profiles are not prepared, a rationale \nand summary of any alternative methods should be provided.  \n \nDomain 3: Values  and Preferences  \nCriterion 1: Target population perception of value  \nCriterion question: Does the target population feel that the desirable effects are large relative to \nundesirable effects?  \nRelated questions:  \n• How does the target population (i.e., those affected or potentially affected by the disease) v iew \nthe balance of desirable effects versus undesirable effects?  \n• Would patients and caregivers feel that the benefits outweigh the harms and burden?  \n• Does the population appreciate and value the vaccination?  \n \nC\nompletion Guidance: Provide information regarding the perspectives and perceptions of potential \nrecipients about the disease and the vaccine.  Describe the source of target population values and \npreferences for critical outcomes (e.g., targeted research, questionnaires).  Discussion and evidence regarding the possible value to the population due to herd immunity may also be included, where applicable. \n \nD\niscussion  \n \nW\nork groups  may want to consider the following topics:  \n• How much less people value outcomes that occur in the future versus  outcomes that occur now  \n• Potential recipient attitudes to undesirable effects (i.e. how risk averse they are)  \n• Risk perception – whether some segment of the population is inclined to view itself as not at risk \nfor the disease  \n \nI\nf the evidence is limited, wo rk group  deliberations can be used.  If evaluation of values is desirable and \nthere is sufficient time to conduct research, there are existing survey mechanisms that may be used when funding and space are available.  Work groups interested in this should c onsult with the ACIP \nSecretariat.  \n \nCriterion 2: Uncertainty around target population perception of value  \nCriterion question: Is there important uncertainty about , or variability in , how much people value the \nmain outcomes?  \nRelated questions:  \n• How much do individuals value each of the outcomes in relation to the other outcomes (i.e. , \nwhat is the relative importance of the outcomes)?  \n•  Is there evidence to support those value judgements, or is there evidence that the variability in \nthose values is  large enough to lead to different decisions?  \n \nC\nompletion Guidance: It is not anticipated that there will be a need to routinely gather evidence if none \nis currently available; rather, any paucity of information should be indicated here.  However, if the \n10 \n variability is estimated to be so significant that this factor alone could lead to a different decision, this \nshould be indicated and consideration given to obtaining additional evidence. The more likely it is that differences in values would lead to different decisions, the less likely it is that there  will be a consensus \nthat an option is a priority from both an individual and public health perspective and the more \nimportant it is to obtain evidence of the values of those potentially affected by the disease.  \n \nDomain 4: Acceptability  \nCriterion: Acceptability to key stakeholders  \nCriterion question: Is the option acceptable to key stakeholders?   \nRelated question:  \n• Are there key stakeholders that would not accept the distribution of benefits, harms , and costs?  \n• Are there key stakeholders that would not accept the costs or undesirable effects in the short \nterm for the desirable effects (benefits) in the future?  \n \nC\nompletion Guidance: This will often represent the opinion of the work group .  Input  from ACIP \nmembers  may also be obtained through commentary and discussion at meetings and incorporated into \nthe final framework.  Stakeholders may include professional societies, liaison organizations, providers, pharmaceutical companies, advocacy groups, and the general public.  Acceptability may vary across \nstakeh older groups and any such variability, and the rationale  for it , should  be captured here.  Similar to \nother domains, the work group consensus opinion on whether it would be acceptable to the majority of stakeholders will be the basis for the final judgment ; there is not a specified “threshold” to determine \nthe answer.  \n \nD\niscussion  \n \nW\nork groups should carefully consider and define which specific stakeholders ( e.g., providers in \nhealthcare settings, providers in community settings, providers in public health s ettings, healthcare \ndelivery systems, and the  public) are considered in their discussions.  Critical stakeholders for each \ncircumstance may differ and therefore there is no pre -specified list of stakeholders that should always \nbe considered, rather work gr oups should determine those groups that are relevant for their given \nsituation.  Liaison members on work groups can often provide perspective for their organizations that may be useful in deliberations.  \n \nD\nomain 5: Resource Use  \nCriterion: Resource allocation \nCriterion question: Is the option a reasonable and efficient allocation of resources?  \nRelated questions:  \n• What is the cost -effectiveness of the vaccination?  \n• How does the cost -effectiveness of the vaccination vary in any sensitivity analyses?  \n• How does the cost -effectiveness change in response to changes in context, assumptions, model \nstructure, across different studies, etc.?  \n \nC\nompletion Guidance: The objective of this section is to describe the available evidence from cost-\neffectiveness analyses (CEAs)  as well as any major factors that could affect the cost -effectiveness profile \n11 \n of the vaccine. Identify the cost- effectiveness results, including the base- case and a sensitivity range, \nfrom any available cost -effectiveness studies.  When possible, indicate  which assumptions cause the \ngreatest change in results by examining the sensitivity analyses of a study.   If there are two or more \nstudies, identify any major differences between the studies.   Identify any other important factors that \nmay affect the cost -effectiveness profile of the vaccination.  For example, issues identified in other \ndomains of the EtR framework regarding the overall certainty of the evidence for critical outcomes may \nalso be important factors that affect vaccination cost -effectiveness.  \n \nD\niscussion  \n \nW\nork groups should assemble economic evidence on the study question and the intervention strategies \nbeing evaluated.   It may be helpful for the health economic evidence to be assembled in consultation \nwith the ACIP Economics Lead and/or the NC IRD Lead Economist.  The evidence collected can include \nanalyses conducted by independent researchers, the vaccine industry and CDC economists.  The work group lead and the ACIP Secretariat will determine if an internal CDC CEA should be conducted.  This w ill \ngenerally be needed for new vaccines and new recommendations with major programmatic economic impact.  \n \nT\nhe findings from the health economic analyses should be reviewed and presented in accordance with \nACIP guidance on economic studies (https://www.cdc.gov/vaccines/acip/committee/guidance/economic -studies.html\n).  The work group \nshould consider the quality of the CEAs as described by the Second Panel on Cost -Effect iveness in Health \nand Medicine.  4  This may include review of the model design and inputs to determine if the estimates \nare reasonable in terms of disease transmission, intervention effects, vaccine costs, implementation costs, disease outcome costs, and c ommunity vs. patient preferences.  It may be important to \nunderstand and articulate whether there is variability in local epidemiology, infrastructure, or costs that influence impact of the intervention.  \n \nDomain 6: Equity  \nCriterion: Health equity  \nCriterion  question: What would be the impact on health equity?  \nRelated questions:  \n• Are there any groups or settings that might be disadvantaged in relation to the problem or options that are considered?  \n• Are there plausible reasons for anticipating differences in the relative effectiveness of the option for disadvantaged groups or settings?  \n• Are there different baseline conditions across groups or settings that affect the absolute effectiveness of the option or the importance of the problem for disadvantaged groups or settings?  \n• Are there important considerations that should be made when implementing the intervention (option) in order to ensure that inequities are reduced, if possible, and that they are not increased?  \n \nC\nompletion Guidance: Clinical and p ublic health guidelines  need to explicitly consider health equity  \n(Welch et al, 2017). Health inequities are differences in health considered unfair or unjust and could \nhave been avoided . This domain facilitates transparent and explicit consideration of t he impact of the \nintervention when compared with the alternative option on the target population, specifically to identify if any persons would be disadvantaged as a result of the intervention. The identification of factors that \n12 \n may lead to health inequiti es may lead to modified recommendations that apply to the target \npopulation or separate recommendations tailored to disadvantaged groups. Work groups may conduct a \nhigh -level search to identify any publications reporting on issues of health equity or inequity on the topic \nunder consideration. Relevant publications may be qualitative  or quantitative. If no evidence is \nidentified, then the work group should provide additional considerations addressing the related questions to the best of their ability.  \n \nDoma in 7: Feasibility  \nCriterion: Implementation feasibility \nCriterion question: Is the option feasible to implement?  \nRelated questions:  \n• Is the intervention sustainable?  \n• Are there important barriers that are likely to limit the feasibility of implementing the intervention or require consideration when implementing it?  \n• Is access to the vaccine an important concern?  \n• Would the vaccine recommendation have any impact on health equity?  \n• Are there important considerations when implementing the intervention in order to ensure that inequities are reduced, if possible, and that they are not increased?  \n \nCo\nmpletion Guidance: The Implementation Checklist tool (Appendix 3) summarizes potential barriers to \nimplementation and can be used to guide these discussions.  Impact on health equity is a component that factors into several areas of the tool, but any outstanding concerns can be explicitly described.  Information regarding barriers that would be difficult to overcome should be provided.  Implementation \nissue s are not expected to drive the recommendation, but it is possible that implementation \nconsiderations may change the type of recommendation, influence the wording of the recommendation \nor only inform the guidance that accompanies the recommendation.  If th ere are specific factors that \ninfluence the ultimate decision regarding the recommendation or its wording, the rationale would be important to include here.  As with other areas of the framework, if data are lacking this should be stated.  Factors that may  impact guidance accompanying the recommendation may be briefly listed \nhere, with additional information included in the “Additional Considerations” section of the framework.  \n  \nConclusions and Additional Considerations  \nFinally, the conclusions  that the work group  reaches and any additional considerations that the work \ngroup  would like to present regarding the policy question or recommendation are presented in the last \nfour rows of the EtR framework (Appendix 1).  \n \nThe t\nype of recommendation and actual text o f the recommendation are based on the judgments made \nfor all of the criteria and relate directly to the summary “Balance of Consequences” judgement presented in the first row of the conclusions section.  The specific wording of each of the three recommenda tion types will stand alone.  The three recommendation options include: ACIP recommend s \nthe intervention; ACIP  recommend s the intervention  for individuals based on shared clinical decision -\nmaking; and, ACIP does not recommend the intervention ( Even though the Intervention may be used \nwithin FDA licensed indications) . \n \n13 \n The final row of the EtR framework table provides space to emphasize any additional considerations that \nare pertinent to the recommendation, including suggestions for overcoming implementation  barriers, \nproposed monitoring and evaluation needs, and/or areas requiring additional research to inform future decisions.  \n \nSummary of  the ACIP ’s deliberation s and final recommendations  \nA summary of the ACIP discussions regarding the work group recommendations and the final wording \napproved  should be included in  the table ‘Final deliberation and decision by the ACIP .’  This should \ninclude a brief description of the rationale supporting any ACIP modification of, or disagreement with, \nthe work group recommendation. This section will be completed by the ACIP work group lead and the ACIP work group chair collaboratively.  \nAdditional Resources  \n1. Alonso -Coello P, Schünemann HJ, Moberg J, Brignardello -Petersen R, Akl EA, Davoli M, Treweek \nS, Mustafa RA, Rada G, Rosenbaum S, Morelli A. GRADE Evidence to Decision (EtD) frameworks: \na systematic and transparent approach to making well informed healthcare choices. 1: Introduction. bmj. 2016 Jun 28;353:i2016.  \n2. Alonso -Coello P, Oxman AD, Moberg J,  Brignardello -Petersen R, Akl EA, Davoli M, Treweek S, \nMustafa RA, Vandvik PO, Meerpohl J, Guyatt GH. GRADE Evidence to Decision (EtD) frameworks: a systematic and transparent approach to making well informed healthcare choices. 2: Clinical practice guidelines. bmj. 2016 Jun 30;353:i2089.  \n3. Ahmed, F., Temte, J.L., Campos -Outcalt, D., Schünemann, H.J. and ACIP Evidence Based \nRecommendations Work Group (EBRWG, 2011. Methods for developing evidence-based recommendations by the Advisory Committee on Immunization Practices (ACIP) of the US Centers for Disease Control and Prevention (CDC).  Vaccine , 29(49), pp.9171 -9176.  \n4. Schünemann H, Brożek J, Guyatt G, Oxman A. GRADE handbook for grading quality of evidence and strength of recommendations. Updated October 2013. The  GRADE Working Group, 2013. \nAvailable from guidelinedevelopment.org/handbook. 2013.  \n5. Welch, V. A., Akl, E. A., Guyatt, G., Pottie, K., Eslava -Schmalbach, J., Ansari, M. T., ... & \nHultcrantz, M. (2017). GRADE equity guidelines 1: considering health equity in  GRADE guideline \ndevelopment: introduction and rationale.  Journal of clinical epidemiology , 90, 59-67. \n14 \n Appendix 1: ACIP Evidence to Recommendations Framework \n \nQuestion: Overarching policy question to be answered by the guideline panel (ACIP)  using the Evidence to Recommendations (EtR) frame work. \nThe quest ion shou ld be precise and ident ify the specific interv ention, compar ison, and outcome, as w ell as the tar get popul ation and t he setting \n(specific s ubpopul ations) in PICO format.  \nPopula tion: Target popul ation  for vaccine (e.g., a ge range, se x, immune sta tus, pregnancy )    \nIntervention: Vaccination (if appl icable, dosag e and sc hedul e)   \nCompa rison(s): No Vaccination/S tandard  of care/An existing vaccine/O ther prevention option   \nOutcome : Outcome(s) associated with vaccination  (e.g., prevention outcomes or adverse effects)  \n \n \n \n \n \n Background: The addressed PICO question should be described in detail, and important background information for understanding the questio n \nand why a recommendation or decision is needed should be briefly provided.  If a recommendation is preferential or represents off-label use, \nthis should be indicated.  \nInclude sample language: Additional background information supporting the ACIP recommendations on the use of xxx vaccine can be found in \nthe relevant publication of the recommendation referenced on the ACIP website . \nWORK GROUP  JUDGMENTS  EVIDENCE  ADDITIONAL INFORMATION  PROBLEMIs the problem of public health importance?  \n \n  ○ \n○ ○ \n○ \n \n○ \n○ No \nP\nrobably no  \nProbably yes  \nYes \nVaries  \nDon't know  Provide available  scientific evidence on \nburden of  disease, preferably within the  \ntarget population for the  \nrecommendation.  \nI\nf no published evidence is available,  \nprovide expert judgment on the  public \nhealth priority  considerations.  Identify any additional public health  \npriority  considerations, including \nconsideration of disparities.  \n  \n15 WORK GROUP JUDGMENTS  EVIDENCE  ADDITIONAL INFORMATION  BENEFITS & HARMS  How substantial are the desirable \nanticipated effects?  \n○ \n○ \n○ \n○ \n○ \n○ \n○\n○○\n○\n○\n○\n○ \n○ ○ \n○ \n○ ○ Minimal  \nSmall  \nModerate  \nLarge  \nVaries  \nDon't know  Describe the magnitude of the  beneficial  \neffects of vaccination  on individual \n(vaccine  effectiveness, duration of \nprotection) and population  (herd \nimmunity) levels.   Take into consideration: \nIs the baseline benefit similar across \nsubgroups (by age, sex,  pregnancy or \nlactation s tatus, occupation [ i.e., healthcare \nworkers], immune s tatus, r ace, S ES, and \nother gr oups)? \nAre there indirect ef fects that should b e \nconsidered ( e.g.,  herd i mmunity)? \nHow substantial are the undesirable \nanticipated effects?  \n Minimal  \n S\nmall  \n Moderate  \n Large  \n Varies  \n Don't know  Are there undesirable effects of the \nvaccine, either on the individual (e.g., \nadverse events following immunization) or population (e .g., age -shift of disease, \nserotype replacement) levels?  Take into consideration:  \nIs the baseline risk for harm similar across subgroups (see above)?  \nS\nhould there be separate recommendations \nfor subgroups based on harms?  \nDo the desirable effects outweigh the \nundesirable effects?  \nFavors interventionl  \nF\navors comparison  \nFavors both  \nFavors neither  \nVaries  \nDon't know  Describe the balance of benefits of the \nvaccine with possible harms (individual and population level).  \n16 \n  \n \n \n \n \n ○\n○\n○\n○\n○○○\n○\n○\n○\n○\n○\n○\n○\n○\n○\n WORK GROUP JUDGMENTS  EVIDENCE  ADDITIONAL INFORMATION  \nWhat is the overall certainty of this \nevidence for the critical outcomes ? \nEffectiveness of the intervention  \n No  studies found  \n 4 (very low)  \n 3 (low)  \n 2 (moderate)  \n 1 (high)  \nSafety of the intervention  \n No studies found  \n 4 (very low)  \n 3 (low)  \n 2 (moderate)  \n 1 (high)  Please refer to GRADE evidence profiles  for \ndetailed assessment of the certainty of the \nevidence. For more information, please see the\n ACIP Handbook for Developing Evidence -\nBased Recommendations.   If GRADE was n ot used to evaluate the \ncertainty of evidence, please provide \njustification and the method and outcome of any other tools used to evaluate the body of evidence relevant to the critical outcomes.  VALUES  Does the target population feel that the \ndesirable effects are large relative to undesirable effects?  \n No \n P\nrobably no  \n Probably yes  \n Yes \n Varies  \n Don't know  Provide any available evidence on target \npopulation values & preferences related to vaccination and comparative health benefits \nand risks. Describe the source of these \nestimates.  Are values and preferences for relevant \noutcomes measured?  Are the benefits, harms and costs of vaccination valued \ndifferently by different subgroups?  \n  \nIf the target group doesn’t value the intervention, or attributes little value to the \nharms and benefits, consider whether potential education measures are needed.  \n   \n \n  \n17 \n  WORK GROUP JUDGMENTS  EVIDENCE  ADDITIONAL INFORMATION  \nIs there important uncertainty about or \nvariability in how much people value the \nmain outcomes?  \n \n○ \n○ \n○ \n○ \n○ \n \n \n○ \n○ \n○ ○ \n \n○ \n○ \n \n \n○\n○\n○\n○\n \n○\n○Important uncertainty or variability  \nProbably important uncertainty or variability  \nProbabl not important uncertainty or variability  \nNo important uncertainty or variability  \nNo known undesireable outcomes  Please provide available data used to \ndetermine the relative importance that the target population attributes to the desirable and the undesirable outcomes related to the intervention as well as the comparison.  Describe the source of variability, if any.  \n Are there methods for determining values satisfactory for this recommendation?  \n If not, systematic assessment of values and preferences of target group may be \nconsidered.  ACCEPTABILITY  Is the intervention acceptable to key \nstakeholders?  \nNo \nP\nrobably no  \nProbably yes  \nYes \nVaries  \nDon't know  Provide assessment of whether intervention \nwould be acceptable to stakeholders \n(ethically, programmatically, financially, etc.)   RESOURCE USE  Is the intervention a reasonable and \nefficient allocation of resources?  \n No \n P\nrobably no  \n Probably yes  \n Yes \n Varies  \n Don't know  \n Provide summary of cost -effectiveness \nanalyses (CEAs) of the vaccine in the target population. Include base case results and a sensitivity range. Include any other notable findings, for example, specific policy -\nrelevant scenario s.  Overall findings: Summarize the findings \nfrom available CEAs, including major differences in baseline assumptions.  \n Uncertainty: Does the analysis capture the full range of uncertainty? For example, are \nthe findings from the uncertainty of \nevidence ana lysis, identified earlier in this \ndocument (the EtR Framework), appropriately represented in the methods of the CEAs?  \n \nMultiple assessments: Are there multiple CEAs? If so, what are the major differences \nin methods and results?  \n  \n18 \n \n WORK GROUP JUDGMENTS  EVIDENCE  ADDITIONAL INFORMATION  EQUITY  What would be the impact on health \nequity?  \n \n \n ○\n○\n○\n○\n○\n○\n○\n \n○ \n○ \n○ \n○ \n ○ \n○ \n  Reduced  \n Pr\nobably reduced  \n Probably no impact  \n Probably increased  \n Increased  \n Varies  \n Don't know  Summarize the  findings from a review of the \nliterature  addressing issues of health \ninequities or groups who may be disadvantaged.  Consider from the evidence or guideline \npanel:  \n• Are there any groups or settings that might be disadvantaged in relation to the problem or o ptions that are \nconsidered?  \n• Are there plausible reasons for anticipating differences in the relative effectiveness of the option for disadvantaged groups or settings? \n• Are there different baseline conditions across groups or settings that affect the absolut e effectiveness of the option or \nthe importance of the problem for disadvantaged groups or settings? \n• Are there important considerations \nthat should be made when implementing the intervention \n(option) in order to ensure that \ninequities are reduced, if possible, \nand that they are not increased?  FEASIBILITY  Is the intervention feasible to implement?  \nNo \nPro\nbably no  \nProbably yes  \nYes \nVaries  \nDon't know  Are there any barriers to implementation?  \n Please refer to the Implementation \nConsiderations checklist. \n19 \n Balance of \nconsequences  Undesirable \nconsequences  \nclearly outweigh  \ndesirable \nconsequences  \nin most settings  Undesirable \nconsequences \nprobably outweigh  \ndesirable \nconsequences  \nin most settings  The balance \nbetween  \ndesirable and \nundesirable \nconsequences  \nis closely balanced \nor uncertain  \n Desirable \nconsequences  \nprobably outweigh  \nundesirable \nconsequences  \nin most settings  Desirable \nconsequences  \nclearly outweigh  \nundesirable \nconsequences  \nin most s ettings  There is \ninsufficient \nevidence to \ndetermine the \nbalance of \nconsequences  \n ○ ○ ○ ○ ○ ○ \nIs there sufficient information to move forward with a recommendation?  \nYes   ○                                              No   ○    \n \n   \n○ ○ ○ Policy options for \nACIP consideration  ACIP does not recommend the \ni\nntervention*   \n*Intervention may be used within \nFDA licensed indications  \n ACIP recommends the intervention \nfor individuals based on shared \nclinical decision -making    \nACIP recommends the intervention  \n \n \nDraft \nrecommendation \n(text)  Please provide the draft recommendations proposed to ACIP.  \n \nAdditional \nconsiderations  \n(optional)  Please outline any significant additional considerations (e.g., aspects related to implementation, monitoring and \nevaluation, research priorities, etc.).  \n \n \n \nFina\nl deliberation and decision by the ACIP  \n \n20 \n  \n \n Final ACIP \nrecommendation   \n  \n○ ○ ACIP does not recommend the \nintervention * \n*Intervention m ay be used within FDA \nlicensed indications  ACIP recommends the intervention for \nin\ndividuals based on shared clinical \ndecision -making    \n○ ACIP recommends the intervention  \n \nAdditional ACIP \nconsiderations  \n Wording as accepted in the guide  \n21 \n Appendix 2 When to Prepare GRADE Evidence Profile  Algorithm  \n \n \n \n \n\n22 \n Appendix 3 Implementation Considerations Checklist", "summary": "1            A CIP Evidence to Recommendation User’s Guide    October 1 , 2020 2    Contents   Introduction .................................................................................................................................................. 3   How to Use This Guide  .................................................................................................................................. 3   The EtR Framework …", "source_url": "https://www.cdc.gov/acip/evidence-based-recommendations/index.html", "pdf_url": "https://www.cdc.gov/acip/media/pdfs/2024/09/ACIP-EtR-Users-Guide_October-1-2020.pdf", "case": "acip", "sub_case": "other", "tags": ["acip", "cdc", "vaccines", "other"], "page_count": 22}
{"title": "01 Pebsworth hepatitis b 508", "content": "Hepatitis B Virus Vaccine\nBirth Dose\nVicky Pebsworth, PhD, RN\nAdvisory Committee on Immunization Practice\nChildhood/Adolescent Schedule Workgroup\nDecember 4, 2025\n1\nPresentation Overview\n•Introduction and Policy Context\n•Burden of Disease\n•Efficacy\n•Safety\n•Conclusions\n2\nIntroduction to Policy Context\nPolicy Request \n•Assess the current recommended schedule, including the use \nof a universal birth dose of Hepatitis B Virus (HBV) vaccine in children whose mothers test negative for HBsAg at delivery\n•Why Are We Here Today?\nFeedback from stakeholders\nMisalignment of existing recommendations in most developed \ncountries\nProlonged time since last comprehensive review as per ACIP’s charter\n3\n•Rising transmission of acute hepatitis from 1960s to the mid -1980s due \nto blood -borne exposures in high- risk groups\n•Introduction of plasma -based vaccine in 1981,  high -risk groups targeted\n•Concerns over vaccine safety, technology changes, reduced liability\n•Evolution of ACIP birth recommendations during the 1980s\n•Dissatisfaction with targeting strategy, ambitious new strategy proposed\n•Leap to universal birth dose made in 1991How Did We Get to Where We Are Now?\nRapid Rise of Reported Acute U.S. Cases of Hepatitis B\n - 5,000 10,000 15,000 20,000 25,000 30,000\n1965 1970 1975 1980 1985 1990Source: CDC National Center for HIV, Viral Hepatitis, STD, and Tuberculosis Prevention, Viral Hepatitis Division, Epidemiology and Survei llance Branch\n•New Vaccine Licensed in 1981\n•Safety Concerns Related to Donor Source Material in Plasma -Derived \nVaccine\n•Availability of New Recombinant Technology Platform and Hepatitis B \nAntigen- based Product Manufactured in Yeast\n•Approval of the National Childhood Vaccine Injury Act in 1986\n•Policymaker Support Factors That Affected Policy Shifts\n“If vaccinations were given universally at birth to infants in\npopulations that have a high rate of perinatal HBV transmission,and with childhood immunizations to infants in other parts ofthe world, a worldwide cohort of persons with protection fromthis long -term infection would be established. ”\n“In the United States, selective immunization of groups at risk ofinfection has not been effective in lowering the overall incidence\nof disease. ”Worldwide Elimination of Hepatitis B Transmissions: \nWe Have the Way, We Need the Will\nEvolution of ACIP Recommendations:\nInfant Target Groups, Treatments/Vaccines\nACIP \nmeetingTarget group Infant treatment Vaccine type Recommendation change logic\n6/25/1982 Infants  born to \nHBsAg+ mothersFirst infant PEP\n•HBIG at birth\n•Vaccine at 3 monthsHeptavax  licensed \n11/16/81 Recommended for high- risk groupsNew vaccine licensed. \nNumerous risk groups targeted\nInfant treatment timing unclear\n6/1/1984 Infants  born to HBsAg+ mothersRefined infant PEP•HBIG within 12 hours of birth\n•Vaccine with 7 daysHeptavax 1983 Lancet study tested 3 different dosing schedules w/HBIG & vaccine. Schedule B \nwas the rec’n\n6/7/1985 Infants  born to \nHBsAg+ mothersConcurrent PEP dosing•HBIG and vaccine <12 hoursHeptavax 1984 Lancet study finds no interference with \nHBIG and vaccine. \n1985 JAMA study doses concurrently\n6/19/1987 Infants  born to \nHBsAg+ mothersConcurrent PEP dosing•HBIG and vaccine <12 hoursRecombivax -HB licensed \nand recommended\nHeptavax  New vaccine licensed\nConcerns over plasma vaccine citedConcurrent dosing schedule kept\n11/22/1991 Universal infant vaccinationVaccination before hospital discharge, no later than 2 months, added to childhood scheduleRecombivax -HB\nEngerix -BConcerns w/failure of targeted policy\nSafety in infant/child trials cited\n12/23/2005 Universal infant \nvaccinationVaccination within 12- 24 hrs of birth Recombivax -HB\nEngerix -BProvide a “safety net” for medical errors\nEliminate “flexible”/”inconsistent” practices\nMotivations to Ask The Question? \nWhat Are We Trying to Accomplish Today?\n•Address Stakeholder/Parent Dissatisfaction\n•Report on the required periodic review conducted by the Workgroup \n•Consider policies that: \n•are better aligned with other countries similar to ours\n•Are based on evidence and target the needs of high -risk persons and \npopulations \n•Explicitly consider the principles of public health and vaccination ethics\n9\nThe Importance of Stakeholders\n•Terms of Reference – IOM Stakeholder \nConcerns\n2002 - Multiple Immunizations and Immune Dysfunction\n2013 - The Childhood Immunization Schedule and Safety: Stakeholder \nConcerns, Scientific Evidence, and Future Studies\n•Stakeholder Surveys\nOregon Survey of Hepatitis B Vaccine Refusal in Newborns, 2014\nKFF/Washington Post Survey of Parents, 2025\nStakeholder Feedback\nOregon Survey\n2014\n•5% Refused HBV birth dose \n•8% wanted to wait \n•6% were undecided.  \nWhy?\n•78.1% baby was too young\n•70.4 % vaccine safety concerns \n•43.8% baby was at low risk of \ninfectionKFF/Washington Post Survey\n2025\n•13% skipped/delayed HBV \n•16% skipped/delayed vaccines\n---67% side effects concerns\n---53% vaccine safety doubts\n---51% vaccines not necessary \n---42% not wanting multiple shots\n---35% safety testing lacking\n---26% CDC recommends too \nmany vaccines \n---41% want to space out shots\n---58% little/no confidence in \nfederal agencies\n11\nU.S. Birth Dose Policy is an Outlier Among \nLow -prevalence Nations\n12\n\n•Markman, Putting Public Health Ethics Into Practice\n•Expected health benefits for the target population\n•Potential harms and burdens for all stakeholders\n•Impact on autonomy\n•Impact on equity\n•Expected efficiency\n•Ethics of Vaccination \n•Preserve Health\n•Means -end Proportionality\n•Discretion\n•Parsimony \n-Marckmann G, Schmidt H, Sofaer N, Strech D. Putting public health ethics into practice: a systematic framework. Front Public Hea lth. 2015 \nFeb 6;3:23. doi: 10.3389/fpubh.2015.00023. PMID: 25705615; PMCID: PMC4319377.Public Health and Vaccination Ethics\nPolicy Context Summary (1)\n•Causes of hepatitis B increases in 1970s-80s diminished \nwith targeted measures\n•Universal birth dose set out to eliminate worldwide transmission\n•Other countries with similar incidence and prevalence of Hepatitis B use a selective vaccination practice, and not a universal birth dose\n•Some parent stakeholder groups would like greater flexibility and the ability to decide what is best for their child.  \n14\nPolicy Context Summary (2)\n•Stakeholder dissatisfaction has been documented for 25 years, is \nof societal significance, and creates challenges for immunization policymaking.\n•The belief that universal vaccination can eradicate Hepatitis B was endorsed by leaders and shaped public policy.\n•In response, between 1983 and 1991, ACIP recommendations shifted from an approach that only targeted high- risk infants to \none that targets all infants.\n•The context included the emergence of advanced vaccine technologies and fewer liability concerns.\n15", "summary": "Hepatitis B Virus Vaccine Birth Dose Vicky Pebsworth, PhD, RN Advisory Committee on Immunization Practice Childhood/Adolescent Schedule Workgroup December 4, 2025 1 Presentation Overview •Introduction and Policy Context •Burden of Disease •Efficacy •Safety •Conclusions 2 Introduction to Policy Context Policy Request  •Assess the current recommended schedule, including the use  of a universal birth dose of Hepatitis B Virus (HBV) vaccine in children whose mothers test negative for HBsAg at…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-december-04-05-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-12-04-05/01-Pebsworth-hepatitis-b-508.pdf", "doc_date": "2025-12-04", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 15}
{"title": "02 nevison Hepatitis B 508", "content": "Burden of disease\n•Morbidity trends \n-What has the universal birth dose accomplished compared to more targeted measures?\n•Vertical (perinatal mother- to-child) transmission\n-Targeted vaccination of at -risk infants vs. the universal birth dose?\n•Horizontal transmission in childhood\n-  What evidence exists and has the risk to most American children been overstated?\nSurveillance data: Acute hepatitis B cases are the longest and \nmost consistently reported metric of morbidity\nMMWR 1991,\n“… selective vaccinationof persons with identified risk factors … has notlowered the incidencehepatitis B.”\nData from the National Notifiable Diseases Surveillance System\n•Increased blood screening for HBsAg\n•Sharp declines in post transfusion hepatitis (PTH)\n•Cleaner practices in dialysis\n•Widespread adoption of safer sexual practices\n•Needle exchange\n•Screening and case management for HBsAg+ mothers\nUniversal birth dose contribution to acute case decline is likely very small.Sources of decline in acute hepatitis B cases\nChronic case data raise new questions\nNNDSS began collecting new chronic case data in 2003\nNNDSS =  National Notifiable\nDiseases Surveillance System\n\nIncreasing new chronic cases of hepatitis B\nin older adults after 2020 \nUpticks after 2020\nalso seen in adults30-39, 40- 49, and\n50-59 years old.\nData from National Notifiable\nDiseases Surveillance System\n\nInfant morbidity\nData from the National Notifiable Diseases Surveillance SystemCDC model of \nperinatal infections:\nYear     # of Cases\n2015 :   952 (Ko et al. 2016)\n2023:   601  (CDC staff)36              7           \n•Acute cases have declined sharply from peak in 1985 for multiple reasons.\n•New chronic cases have been increasing among older adults after 2020.\n•Perinatal cases are down to 36 and 7 in 2015 and 2023, respectively, but\n    CDC model predicts many more cases.Summary of hepatitis B morbidity trends\nModeling perinatal infections\nEstimate begins by tabulating how many mothers are HBsAg+,\ni.e., chronic carriers of hepatitis B virus\nMajority of HBsAg+ mothers in US are foreign -born\nKoneru et al., 2019, Table 2 excerpts; estimated for 2015\nMaternal country \nof birthTotal Births HBsAg+ prevalence \n(%)Estimated births to \nHBsAg+ women\nTotal 3,978,500 20,678  (15,625 -30,640)\nUS-born total 3,070,700 0.17 (0.07 -0.39) 8,296  (4,031 -17,100)\nNon-US-born\nTotal 857,105 11,981  (11,395 -12,762)\nAfrica 64,228 3.42 (3.27 -3.96) 2,197 (2,100 -2,543)\nAsia\nEast Asia 66,384 8.73 (8.52 -8.93) 5,795  (5656 -5928)\nSoutheast Asia 62,044 3.92 (3.76 -4.08) 2,432  (2,333 -2531)\nModeling perinatal cases\nbased on Ko et al., 2016 model\nBirths to HBsAg+ \nwomen \n~ 18,000 \nSuscep tib le \nI nfantsMothe r \nHBe Ag +M other HBe Ag -F = 70% 1-F = 30%\nT ransmission rate K+ = 90%T ransmission rate K- =  5-20%Perinatal \nI nfections\nChronic rate L = 90%Chronically \ninfected infantsChang et al., 2007;\nKo et al., 2016Mothe r\nHBe Ag -\nPEPUpdated input from C DC\n in response to A C I P query .\nPEP (post exposure prophylaxis)\nPEP includes hepatitis B vaccine and HBIG at birth\nHBsAg+ mothers \nscreened 88%\nI nfants with\ntimely PEP at \nbirth  98.5%I nfants with no \nPEP at birth \n1.5%I nfants with no \nPEP at birth  \n20.5%\nM other HBe Ag -\nSuscep tib le \ninfants 9%HB sA g+ mothers\nunscreened  12%\n8% failed\n PEPI nfants with \ntimely  PEP at \nbirth  79.5%\n8% failed PEP\n601 chronically infected infants in 2023 but NNDSS reports only 7 !\nUpdated inputs from\nC DC  in response to ACIP q u e r y.\nSuscep tib le \ninfants 27%\nPerinatal (mother -to-child) transmission summary\n•Risk is isolated to ~0.5% of pregnancies, mainly immigrants from high endemicity \ncountries.\n       - Add hep B to immigrant medical examination.\n•Improve screening measures in prenatal care and delivery.  PEP is effective in \npreventing transmission!\n•CDC’s Ko et al. model may overestimate perinatal cases.\n      -U.S.  infants are not all equally at risk - many mothers intentionally decline birth dose.\n      - Other inputs (screening rate, PEP failure rate) may be too pessimistic.\n•Little published evidence documenting horizontal transmission.\n•A single modeling study, Armstrong et al. [2001], raised \nconcerns that all young children in the U.S. are at significant \nrisk for horizontal transmission of hepatitis B .  \n•The model estimated ~ 16,000 cases/yr in children age 0- 9 \nyears old in the pre -vaccine era due to horizontal transmission, \nhalf in Asian immigrants, half in the general U.S. population.Modeling horizontal transmission in childhood\nArmstrong G, Mast E, Wojczynski  M, Margolis H. 2001. Childhood Hepatitis B Virus Infections in the \nUnited States Before  Hepatitis B Immunization, Pediatrics 108(5), 1123 -1128.\nArmstrong 2001 modeled HepB  horizontal transmission based on \nseropositivity v. age in NHANES and among Asian immigrants\n\nIndependent calculation of Armstrong linear fits\nWithout the assumed \nperinatal infection (Po), \nseropositivity is significantly correlated \nwith age only for the \nSoutheast Asian model. \nNHANES seropositivity \nv. age correlation is \nstatistically \ninsignificant with a \nnatural intercept of \n0.22% (perinatal).\n \n\nComparison of 2 SE Asian Groups\nCharacteristic Louisiana (Vietnamese) Wisconsin (Hmong)\nAll, families, US -born children N =1403, 227, 679 N=1183, 161 ,429\nHBV markers used, past or present \ninfectionAnti -HBc Anti -HBc or HBsAg+\nHBV markers used, chronic HBsAg+, anti -HBsIgM - HBsAg+\nUS born, % any HBV (% chronic) 16%, (4%) 14% (6%)\nAsian -born, % any HBV (% chronic) 59% (11%)*      (inferred) 72% (19%)**\n% of children with HBsAg+ moms 9%  (60/656) 16% (69/429)\nReference Mahoney et al., 1995 Hurie  et al., 1992\n* Nguyen and Trevison . 2020. Vietnam a country in transition: BMJ doi:10.1.1136/bmjnph -2020- 000069 \n    does not list hepatitis B among the leading causes of death in Vietnam .\n** In the Asian -born Hmong, 86% -97% of those aged 15 to >40 years had HBV blood markers.\nHorizontal transmission in childhood?\n•Horizontal transmission is rare among most U.S. children …\n•Although it can occur in some high- risk immigrant families\n•Armstrong et al.’s 16,000 cases/year are not supported by NNDSS data \n                                                                                   \n \n                           ~ 400 acute cases/year \n   pre -UBD\nNNDSS =  National NotifiableDiseases Surveillance System\nThe Informed Consent Action Network (ICAN) asked the CDC \nfor “documentation sufficient to reflect any case(s) of \ntransmission of Hepatitis B in an elementary, middle, or \nhigh school setting. ”\nThe CDC responded, “A search of our records failed to \nreveal any documents pertaining to your request. ”Horizontal transmission in childhood – final note\nhttps://icandecide.org/article/cdc -concedes -it-lacks -any-proof- of-hepatitis -b-being -transmitted -in-a-\nschool -setting/\nSummary of burden of disease\nMixed trends in hepatitis B morbidity 34 years after the Universal \nBirth Dose\n- Acute cases have declined sharply for multiple reasons.\n- New chronic cases are increasing since 2020 in adults over 30.\n- Reported perinatal cases are in the single to low double digits thanks to \nP E P.\n          \nModels yield larger estimates than surveillance data  -   cross \nchecks useful\n          - Ko et al. model may overstate perinatal chronic cases.\n          - Horizontal transmission among young children is rare and was strongly \n overstated by the Armstrong et al. model.\nEfficacy and Waning Immunity\nMany studies show reduced antibody levels over time following hepatitis B \nvaccination, especially when vaccination begins in infancy or early childhood.\nAge (years) at the time \nof:Anti-HBs ( mIU/ml )\nBefore booster doseAnti-HBs ( mIU/ml) \nAfter booster dose*\nBooster Primary series GMC % with ≥ 10 (N >10/Ntotal)GMC % with ≥ 10 (N >10/Ntotal)\n< 40 < 5 6.8 32% (19/59) 98.2 83% (25/30)\n35 to 39 5 to 9 24.9 61% (30/49) 134.2 94% (16/17)\n40 to 49 10 to 19 22.8 64% (58/90) 275.7 89% (17/19)\n≥ 50 ≥ 20 8.5 40% (18/45) 179.4 89% (17/19)Native Alaskans vaccinated for hepatitis B between \nages 5 -19 years had highest titers 30 years later\nBruce et al. 2016. Protection and  antib od y levels after Hep atitis B vaccine: Results of a 30 -year follow -up study and response t o a \nbooster dose, JID 214: 16- 22. (Tables 1,3)* B ooster dose was given to 85 people with titers < 10 m IU/ml as well as an \nadditional N=36 people who were not boosted in the 22 -year follow -up.\nBy age 16 -19 years, most US children vaccinated as infants had low \nantibodies, but most responded well to a booster dose\nMiddleman et al. 2014. Duration of protection after infant Hep atitis B vaccination series, Ped iatrics 133(6) .Gr o u p  1 : Fir s t\n vaccine ≤ 7 days Gr o u p  2 : Fir s t vaccine ≥ 4 weeks Group 1, % Group 2, % Total, % P value\n1st dose \n≤7 d ays1st dose \n≥ 4 weeks\nBaseline \nseroprotection16.7 % 33.9 % 24.1 % < 0.0001\nPostchallenge  \ndose seroprotection90.4 % 93.9 % 91.9 % 0.2T able 2 L evels of Seroprotection  (anti -HBs Tite r ≥ 10 IU/m L) b y Group\nWaning immunity also seen among teenagers vaccinated as \ninfants in NHANES data\nCohorts most likely \nvaccinated as infants\nData compiled by CDCHepatitis Division\n•Anti -HBs titers wane the most rapidly in children who begin \ntheir primary series as infants, especially as newborns.\n•While most vaccinees respond well to a booster dose, some \nof those vaccinated as infants may lack protection when they \nenter their years of highest risk for acquiring hepatitis B.Waning immunity summary and concluding thoughts\nReferences\nArmstrong G, Mast E, Wojczynski  M, Margolis H. 2001. Childhood Hepatitis B Virus Infections in the United States \nBefore Hepatitis B Immunization, Pediatrics 108(5), 1123 -1128\nBruce et al. 2016.  Protection and antibody levels after Hepatitis B vaccine:  Results of a 30 -year follow -up study and \nresponse to a booster dose, The Journal of Infections Diseases, 214(1 July) 16 -22\nChang, M -H. 2007. Hepatitis B virus infection.  Seminars in Fetal & Neonatal Medicine (2007) 12, 160e167.\nHurie  MB, Mast EE, Davis JP. Horizontal transmission of hepatitis B virus infection to United States -born children of \nHmong refugees. Pediatrics . 1992;89:269– 273\nKlevens  RM, Liu S, Roberts H, Jiles RB, Holmberg SD.  2014. Estimating acute viral hepatitis infections from nationally \nreported cases.  Am J Public Health, 104(3): 482 -487\nKoneru, A. 2019. Estimating Annual Births to Hepatitis B Surface Antigen –Positive Women in the United States by \nUsing Data on Maternal Country of Birth Public Health Reports 134(3)\nKo SC et al. Estimated Annual Perinatal Hepatitis B Virus Infections in the United States, 2000 -2009. J Pediatric Infect \nDis Soc. 2016 Jun;5(2):114- 21\nMahoney FJ, Lawrence M, Scott C, et al. Continuing risk for hepatitis B virus transmission among Southeast Asian \ninfants in Louisiana. Pediatrics . 1995;96:1113– 1116 \nMcQuillan GM, Townsend TR, Fields HA, et al. Seroepidemiology  of hepatitis B virus infection in the United States. \n1976 to 1980. Am J Med.  1989:87:5S –10S\nMcQuillan GM, Coleman PJ, Kruszon -Moran D, et al. Prevalence of hepatitis B virus infection in the United States: the \nNational Health and Nutrition Examination Surveys, 1976 through 1994. Am J Public Health. 1999; 89:14– 18\nMiddleman et al. 2014. Duration of protection after infant Hepatitis B vaccination series, Pediatrics 133(6)\nMMWR 1991. CDC/ACIP, Hepatitis B Virus: A Comprehensive Strategy for Eliminating Transmission in the United \nStates Through Universal Childhood Vaccination: Recommendations of the Immunization Practices Advisory Committee (ACIP), MMWR, November 22, 1991 / 40(RR -13);1- 19, \nhttps://www.cdc.gov/mmwr/preview/mmwrhtml/00033405.htm\nOtt et al. The risk of perinatal hepatitis B virus transmission: hepatitis B e antigen ( HBeAg ) prevalence estimates for all \nworld regions BMC Infectious Diseases 2012, 12:131 http:// www.biomedcentral.com /1471 -2334/12/131     \nSmith E.A. et al., 2012. The national Perinatal Hepatitis B Prevention Program 1994 -2008. Pediatrics 129(4). \ndoi:10.1542/peds.2011- 2866\nFor more information, contact CDC\n1-800- CDC- INFO (232 -4636)\nTTY:  1 -888- 232- 6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.\nClosing Slide / Disclaimer", "summary": "Burden of disease •Morbidity trends  -What has the universal birth dose accomplished compared to more targeted measures? •Vertical (perinatal mother- to-child) transmission -Targeted vaccination of at -risk infants vs. the universal birth dose? •Horizontal transmission in childhood -  What evidence exists and has the risk to most American children been overstated? Surveillance data: Acute hepatitis B cases are the longest and  most consistently reported metric of morbidity MMWR 1991, “……", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-december-04-05-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-12-04-05/02-nevison-Hepatitis-B-508.pdf", "doc_date": "2025-12-04", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 26}
{"title": "03 blaxill Hepatitis B 508", "content": "Safety Review of Hepatitis B Birth Dose Vaccination\nCDC Advisory Committee on Immunization Practices meeting \nMark F. Blaxill, MBA\nDecember 4, 2025Office of the Director\n\nSafety of the hepatitis B vaccine\n•Clinical trials\n•Post -licensure safety studies\n•IOM and VICP on vaccine -related injuries\n•Animal models\n•There were no randomized placebo -controlled trials in infants; cited trials used \nshort follow up periods of 7 days or less and discounted safety concerns\n•CDC/ISO’s “rapid systematic review” of post -licensure safety studies reveals \nconcerns but evidence of chronic, late -onset effects was not presented\n•IOM Safety of Vaccine reports have highlighted the absence of evidence to \nassess potential adverse effects in over 30 endpoints \n•VICP has processed large numbers of HBV related claims, compensating many\n•Mechanisms of injury, especially immune activation, reported in animal models Overview of Hepatitis B Vaccine (HBV) Safety:\nSafety evidence is limited and often concerning\nClinical trials on infants/children cited for birth dose of \nRecombivax HB or Engerix -B in 1991 ACIP recommendation\nTrial \npublicationVaccine Control \ngroupSample size and \ncompositionSafety follow up \nperiodSafety findings\nZajac et al, \n1986Recombivax HB None 79 children, ages 1 -12 years5 days after each dose18% “systemic” complaints:\n“fatigue, weakness, \ndiarrhoea or irritability. ”\nStevens et al,  \n1987Re co m b iva x HB Plasma vaccine122 infants\n39 plasma/83 recombinantAsia n -Am e rica n\nHBs Ag + / HBe Ag + mothers7 days after each dose1 death in recombinant group due to “ inoperable congenital malformation”\nA ndre et al,  1989En g e rix -B None 1187 neonates Up to 3 days after each dose96% “had no reaction to the \nvaccine. ”\n2.5% mild/moderate fever\n“Symptoms of encephalitis…\n“Encephalitis can be dangerous in infants. Watch for fever , lethargy ( weakness or drowsiness), poor feeding, \nvomiting, body stiffness, unexplained/unusual irritability or crying”\nSource: Encephalitis | National Institute of Neurological Disorders and Stroke“Systemic” clinical complaints in children reported in Zajac et al (1986)\n\nISO’s “rapid systematic review” of hepatitis B post -licensure safety data\n(ISO, 9/18/25) included 20 studies— presented findings from 9 of 20\nCategories Unvaccinated or no vaccine as control Vaccine(s) as control\nBirth dose defined as <24 hours\nLinder et al, 1999\nLewis et al, 2001 (VSD)\nMorgan et al, 2025Bassily et al, 1995\nYerushalmi et al, 1997\nBirth dose defined as 0 -8 days\nEriksen et al, 2004 (VSD) Greenberg et al, 2002Lopez et al, 2002\nWood et al, 2018\nBirth dose defined as <30 days\nGallagher & Goodman, 2010 (NHIS, ASD)Geier et al, 2015 (VSD, Tics)Geier et al, 2016 (VSD, Dev Delay)\nGeier et al, 2017 (VSD, Emot Disturb)\nGeier et al, 2018 (VSD, prem puberty)Verstraeten et al, 2003 (VSD)\nVAERS studies (3)\n-Niu et al, 1996 \n-Niu et al, 1999 (death)\n-Haber et al, 2018Sapru et al, 2007\nGeier et al, 2013 (ASD)\nISO’s “rapid systematic review” of hepatitis B post -licensure safety data\n(ISO, 9/18/25) included 20 studies— presented findings from 9 of 20\nCategories Unvaccinated or no vaccine as control Vaccine(s) as control\nBirth dose defined as <24 hours\nLinder et al, 1999\nLewis et al, 2001 (VSD)\nMorgan et al, 2025Bassily et al, 1995\nYerushalmi et al, 1997\nBirth dose defined as 0 -8 days\nEriksen et al, 2004 (VSD) Greenberg et al, 2002Lopez et al, 2002\nWood et al, 2018\nBirth dose defined as <30 days\nGallagher & Goodman, 2010 (NHIS, ASD)Geier et al, 2015 (VSD, Tics)Geier et al, 2016 (VSD, Dev Delay)\nGeier et al, 2017 (VSD, Emot Disturb)\nGeier et al, 2018 (VSD, prem puberty)Verstraeten et al, 2003 (VSD)\nVAERS studies (3)\n-Niu et al, 1996 \n-Niu et al, 1999 (death)\n-Haber et al, 2018Sapru et al, 2007\nGeier et al, 2013 (ASD)\nEarly post -licensure study described unexplained fever \nin neonates in the year after HBV introduction in Israel\nOR= 2.16“In conclusion, we found that an \nincreased incidence of unexplained \nneonatal fever, which resulted in \nevaluation for sepsis, administration of \nintravenous antibiotics, and prolonged \nhospital stay, may be associated with \nvaccination against hepatitis B on the \nfirst day of life. “\nPost -licensure safety studies with unvaccinated group and \nnegative/protective findings show healthy vaccinee effect (HVE)\nStudy Condition(s) \nexaminedFinding HVE effects in sample \nselection\nIncluded in 9/2025 ACIP safety review\n1. Lewis et al, 2001 ( VSD) Fever, sepsis, allergies, seizures\nTesting frequencyNo differences0.73 OR for testsExclusions of preterm, LBWUnexplained testing frequency\n2. Ericksen et al, 2004 ( VSD)Death Lower death rate \nin exposedUnvaccinated sample mean birth wgt <44% of vaccinated\n3. Morgan et al 2025 \n(Australia)Bronchopulmonary dysplasia in preterm0.83 RR “it is not known how clinician perception of the stability of the newborn affects the decision to vaccinate or not”\nEriksen et al, 2004 (VSD)\nHVE effect: unvaccinated vs. vaccinated neonates\n•<44% of median birth weight\n•11 weeks lower median gestational age\n•Only 5% of 1993- 98 cohort deaths were in \nvaccinated infants, 72 of 1363\n\nStudy design \n(1) identified all neonatal deaths in NCK and SCK from 1993 -98 \n(2) determined cases that had been vaccinated with HBV \n(3) selected 2– 4 matched HBV -unvaccinated controls for each HBV -vaccinated neonatal death\nMatching based on “days of life” category (0 -1, 2- 5 and 6 -28), birth year, sex and HMO\n(4) determined pre -existing illness and the causes of death\n(5) Categorized deaths as “expected” or “unexpected” in a blinded review\n(6) assessed the clinical plausibility that HBV contributed to death \n(7) assessed SIDS rates, searched for unvaccinated SIDS cases beyond matched sample\n(8) Compared maternal and perinatal factors in both groupsEriksen et al, 2004: death assessment method \nEriksen et al, 2004: Death assessment in matched samples\nPrimary cause of death Vaccinated Unvaccinated\nTotal deaths 72 196\n“Expected” 50 (69%) 128 (65%)\n“Unexpected” 22 (31%) 68 (35%)\nSIDS 8 0\nSepsis after birth 7 4\nNecrotizing enterocolitis (NEC) 3 29\nInsufficient information 2\nCNS hemorrhage 1 15\nLaryngeal edema 1\nPulmonary/other hemorrhage 0 5\nOther - 15\nISO’s “rapid systematic review” of hepatitis B post -licensure safety data\n(ISO, 9/18/25) included 20 studies— presented findings from 9 of 20\nCategories Unvaccinated or no vaccine as control Vaccine(s) as control\nBirth dose defined as <24 hours\nLinder et al, 1999\nLewis et al, 2001 (VSD)\nMorgan et al, 2025Bassily  et al, 1995\nYerushalmi et al, 1997\nBirth dose defined as 0 -8 days\nEriksen et al, 2004 (VSD) Greenberg et al, 2002Lopez et al, 2002\nWood et al, 2018\nBirth dose defined as <30 days\nGallagher & Goodman, 2010 (NHIS, ASD)Geier et al, 2015 (VSD, Tics)Geier et al, 2016 (VSD, Dev Delay)\nGeier et al, 2017 (VSD, Emot  Disturb)\nGeier et al, 2018 (VSD, prem puberty)Verstraeten  et al, 2003 (VSD)\nVAERS studies (3)\n-Niu et al, 1996 \n-Niu et al, 1999 (death)\n-Haber et al, 2018Sapru et al, 2007\nGeier et al, 2013 (ASD)\nAdditional studies with unvaccinated comparisons listed—but \nnot presented —in 9/2025 ACIP safety review presentation\nStudy Condition(s) examined Finding Comments\n1. Verstraeten  et al, 2003 Neurodevelopmental disorders (VSD) No significant associations Hg/HBV exposure within 1st month\n2. Gallagher & Goodman, 2010 Autism (NHIS) 3.002 OR in males Vaccinated w/in 1st month\n3. Geier et al, 2015 Tics (VSD) 1.59 OR total\n•1.65 OR in malesHg/HBV exposure within 1st month\n4. Geier et al, 2016 Developmental delay (VSD) 1.22 RR Hg/HBV exposure within 1st month\n5. Geier et al, 2017 Emotional disturbance (VSD) 1.34 OR\n•1.36 OR in malesHg/HBV exposure within 1st month\n6. Geier et al 2018 Premature puberty (VSD) 1.80 OR\n•1.87 OR in femalesHg/HBV exposure within 1st month\n7. Niu et al, 1996 VAERS reports: 1/1991 -5/1995\n“neonates” <1 month and \n“infants” < 1 year“No unexpected adverse \nevents in neonates and \ninfants”Neonates:13 of 24 SAEs were fever, 4 seizures3 of 6 deaths were SIDS \n8. Niu et al, 1999 VAERS reports: 1/1991 -10/1998 No “clear increase in neonatal deaths”18 death reports within 1st month12 SIDS cases, 3 initially SIDS\n9. Haber et al 2017 VAERS reports, inc. infants: 2005 -15 No “new or unexpected safety concerns”27 deaths, 64 SAEs  in 1\nst month,  \n197 SIDS cases\n4 VSD studies with consistent methodologies found increased risk of injury \nfor chronic, late -onset conditions from HBV in 1st month\n0.511.52\nTics   \n               Developm  \ndelayEmotional \ndisturbancePremature \npubertyT M F\nT M F T M FT M FOdds\nRatioLegend\nT= total\nM= maleF= female\nIOM studies of causal relationships with HBV (1)\nCondition 1994 2002 2012\nDeath\nDeath following anaphylaxis Y\nSIDS\nAll other causes\nArthritis \nAcute Arthropathy\nChronic Arthropathy\nPsoriatic, onset or exacerbation\nReactive, onset or exacerbation\nRheumatoid, onset or exacerbation\nJuvenile Idiopathic, onset or exacerbation\nAnaphylaxis Y Y\nBrachial Neuritis \nErythema Nodosum\nSystemic Lupus Erythematosus, Onset or ExacerbationVasculitis, onset or exacerbationPolyarteritis Nodusa , onset or exacerbation\nDiabetes, Type 1\nFibromyalgiaEvidence is: \ninsufficient to accept  \nor reject , \nestablishes (Y), or \nfavors rejection of (N)causality\nIOM studies of causal relationships with HBV (2)\nCondition 1994 2002 2012\nEncephalitis\nEncephalopathy\nSeizures\nGuillain -Barre Syndrome\nEncephalomyelitis, Acute Disseminated \nDemyelinating Disorder, Central Nervous System,  1st episode\nDemyelinating Event, first episode, ADULTS\nDemyelinating Event, first episode, CHILDREN\nOptic Neuritis\nMultiple Sclerosis\nMultiple sclerosis, incident/onset,  ADULTS N\nMultiple sclerosis, incident/onset,  CHILDREN\nMultiple sclerosis relapse,  ADULTS N\nMultiple sclerosis relapse,  CHILDREN\nTransverse Myelitis Neuromyelitis OpticaChronic Inflammatory Disseminated PolyneuropathyEvidence is: \ninsufficient to accept  \nor reject , \nestablishes (Y), or \nfavors rejection of (N)causality\nVaccine Injury Compensation Program (VICP)\nAdult compensation claims for hepatitis B vaccine total $92 million\nMultiple sclerosis, transverse myelitis, GBS, encephalitis, \nalopecia,  fibromyalgia,  thrombocytopenia,  hypotension,  arthritis,  uveitis,  and optic neuritis are outcomes both compensated by V I C P and listed in the Re co m b iva x  HB \nand/or En g e rix -B  package inserts.\nVaccine Injury Compensation Program (VICP)\nChildren’s compensation claims for hepatitis B vaccine\n$18 million in  payments for hepatitis B vaccine alone.  \nVICP has p aid an additional $80 million for claims due to hepatitis B  in combination with other vaccines.\nChildren’s claims for hepatitis B vaccine are more \ncommonly denied than compensated by VICP \nAnimal models of hepatitis vaccine birth dose\nStudy Model Selected findings\nImmune Brain Behavioral\nStudies finding altered development\nYang et al, 2016 mice Th2 bias ↓ hippocampal neurogenesis ↑ anxiety ↓locomotor activity\nWang et al, 2018 mice ↑ IL-4 levels ↑ neuroinflammation ↓ spatial learning & memory\nZhou et al, 2024 mice CD8+ infiltrate CNS ↓ hippocampal neurogenesis ↑ anxiety \nLi et al, 2015 rats Th2 shift ↓ synaptic plasticity --\nHewitson et al 2010a macaques -- -- Delayed neonatal reflexes\nHewitson et al 2010b macaques -- Altered amygdala maturation --\nStudies finding no changes\nCurtis et al 2015 macaques -- -- No consistent evidence of deficits\nGadad  et al 2015 macaques -- No evidence of neuropathology No evidence of aberrant behavior\nImmune activation after infant birth dose in rodent models \nleads to neurodevelopmental and behavioral impairments\nStudy Immune findings Immune -> \nbrainBrain findings Brain -> \nbehaviorBehavioral \nfindings\nLi et al, 2015 \n(rats)• Anti -HBs response; Th2 bias at 8 \nwks\n• ↑ TNF-α, ↑IL-6, ↓ IFN-γ, ↓BDNF, ↓ \nIGF-1•  Serum &  hippocampal \ncytokines track together• IFN -γ/IL-4 ratio tracks with \nhi ppocampal  B DN F  &  I G F -1I mpai red DG  L T P\n• ↓ dendritic spine density, \n↓ stubby spi nes\n• ↓ synaptophysin, PSD -95, \nNR2 A, NR2 B-- --\nY ang et al \n2016 (mice)•  H i ppocampus ( 6 wks ): ↓ IFN-γ, ↓\nBDNF, ↓ IGF-1; ↑ TNF-α, ↑IL-1β, ↑\nIL-6\n•  Serum T h2 bias ( ↓ IFN-γ/IL-4)\n• HEL+ a lu m  reproduces \nphenotype;  alum alone does not• IFN -γ/IL-4 correlates with \nhi ppocampal  B DN F /I G F -1 \n&  neurogenesis markers• ↓ Brd U +, ↓ Brd U +/DCX +, ↓ \nBrd U +/NeuN+\n• Impaired CA1 L TP at 8 \nwks•  E arly neurogenesis &  \ncytokine changes precede \nbehavior• OFT: ↓ distance, ↓ rearing, \n↓ center time\n• EPM: ↓ open- arm  activity\n• MWM: im paired learning &  memory ( normal  swi m speed)• Deficits only at 8 wks\nW ang et al,  \n2018 (mice)•  Sustained ↑ IL-4 in serum &  \nhippocampus\n•  Delayed neuroinflammation ( ↑ \nTNF-α, IL-1β, IL-6)\n• Se ru m  IL -4 correlates with \nhi ppocampal  I L -4• Neonatal IL-4 reproduces\nHBV outcome\n• HBV & IL -4 ↑BBB \nperm eability t o  IL -4\n• ↓IL-4 R in  hippocampus•  Delayed hi ppocampal  \nneuroinflammation• Ea rly IL -4 surge → later \nneuroinflammation → \nbehavior deficitsDelayed spatial cognition\nZhou et al,  \n2024 (mice)•  HB V  induces effector memory \nCD8+ T -cells\n• CD8+ T cells: ↑ CXCR6; ↓ Arid 5a , \nMc1r, Flt3, etc.\n• ↑ effector -memory C D4+ and \nCD8+ T cells• ↑ TNF-α+ / IFN-γ+ CD8+ cells•  C D8+ T  cells enter C NS  \nvia CXCL16/ CXCR6 axis•  A doptive transfer of HB V -\nT cells → ↓ neurogenesis• ↓ K i67+ and ↓  DCX+ cells \nin DG\n• CXCL16 from  glia recruits CD8+ cells• CD8 infiltration → \nanxiety -like behavior• OFT: ↓ center time, ↓ \nexploration\n• EPM: ↓ open- arm  activity\n• ↑ anxiety -like behavior\nThe safety of the universal birth dose (UBD) was not studied, pre -licensure, \nin randomized, placebo -controlled, extended follow -up trials. \nPost -licensure studies have in some cases been confounded by the healthy \nvaccinee affect; others have found evidence of chronic, late onset adverse \neffects. \nIOM Safety of Vaccine reports have highlighted the absence of evidence to \nassess potential adverse effects in over 30 endpoints \nAnimal models provide evidence for risk of immunological activation and \nneurobehavioral impairment. Conclusions", "summary": "Safety Review of Hepatitis B Birth Dose Vaccination CDC Advisory Committee on Immunization Practices meeting  Mark F. Blaxill, MBA December 4, 2025Office of the Director  Safety of the hepatitis B vaccine •Clinical trials •Post -licensure safety studies •IOM and VICP on vaccine -related injuries •Animal models •There were no randomized placebo -controlled trials in infants; cited trials used  short follow up periods of 7 days or less and discounted safety concerns •CDC/ISO’s “rapid systematic…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-december-04-05-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-12-04-05/03-blaxill-Hepatitis-B-508.pdf", "doc_date": "2025-12-04", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 25}
{"title": "04 pebsworth hepatitis b 508", "content": "Summary of Information\nChildhood/Adolescent Schedule Workgroup\nHepatitis B Virus Vaccine Birth Dose \nDecember 4, 2025\nOverview\n•Childhood/Adolescent Schedule Workgroup \n•Workgroup Process\n•Workgroup Findings\n•Proposed Voting Language\n1\nWorkgroup Members\nACIP members \nKirk Milhoan, MD, PhD \nMartin Kulldorff , PhD\nEvelyn Griffin, MDVicky Pebsworth, PhD, RN \nOutside Experts\nBrian Morse, MD, PhD, Christine Stabell Benn, MD\nEx-officio\nTracy Beth Hoeg, MD, PhD\n2\nPolicy Request\nAssess the use of a universal birth dose of \nHepatitis B vaccine in children whose mothers are \nHBsAg- negative.\n(Which necessarily involves more than the birth dose.)\nTerms of Reference Document \n“Review the efficacy and safety of the \nimmunization schedule for children and \nadolescents, identify efficacy and safety \nproblems, and address stakeholder concerns. ”  \n3\nMotivation and Public Health Importance\n•Feedback from stakeholders\n•Misalignment with existing recommendations in \nmost developed countries\n•Prolonged time since last comprehensive review as per ACIP’s charter\n4\nWorkgroup Process\n•September 18 -19, 2025, ACIP Meeting\n•Request to CDC for Additional Information to Address \nACIP Questions\n16 questions: descriptive safety and  data\n•Workgroup Meetings\nBetween 10/17/25 and 11/24/25, the workgroup met 7 times\n•Workgroup Process - Presentations, Discussions, and \nStraw Polls\n12 presentations by CDC staff, workgroup members, and invited ad \nhoc experts that covered clinical ethics, non- specific vaccination \neffects, aluminum adjuvant exposures, clinical practice challenges and solutions, and the Alaska Hepatitis B vaccine trials.  \n5\nWorkgroup Findings:\nAreas of Full/Nearly Full Agreement (1)\n•Hepatitis B virus can be \ntransmitted vertically and \nhorizontally  to infants, is a \nserious disease, and can be prevented by vaccination with the HBV vaccine\n•There is uncertainty  about \ntrue rates of incidence, \nprevalence and horizontal \ntransmission rates•There is uncertainty  about \nwhether all three \nrecommended doses are \nneeded to acquire protection\n•There are gaps in evidence \nand limitations related to evidence of safety (per \nGRADE quality of safety \nevidence is poor)\n6\nWorkgroup Findings:\nAreas of Full/Nearly Full Agreement (2)\n•Infants born to mothers who \ntest positive for HBsAg should \ncontinue to be vaccinated with HBV vaccine and receive hepatitis B immunoglobulin \nsoon after birth\n•Any gaps in screening pregnant \nwomen for HBsAg should be eliminated so that all infants \nreceive appropriate care •Re- screening  of pregnant \nmothers upon admission for \ndelivery should be considered \nso that there are no mothers \nwhose HBsAg is “unknown ” \nwhich should be regarded as a serious quality of care problem, if not a medical error, and a \n“never event”\n•Infants born to mothers who \ntest negative for HBsAg have \nextremely low risk of horizontal infection during childhood and particularly in first months of life \nand therefore, do not need to be \nroutinely vaccinated with the HBV vaccine at birth\n7\nWorkgroup Findings:\nCentral Themes Related to Hepatitis B Preventive Care\nImproving Quality and Appropriateness of Hepatitis B \nPreventive Care\n•screen all pregnant mothers (no unknowns), appropriately treat \nall newborns\nMinimizing AEFI in Vulnerable Newborns \n•avoid unnecessary early life exposures\nFostering Individual -based Decision -making and Respect for \nParental Autonomy \n•permit clinical flexibility and individual risk assessments\nImproving Safety Monitoring and Research \n•close evidence gaps\nModifying US Policy, Consider other Countries\n•return to a targeted and successful strategy more in line with other \ndeveloped countries with low endemicity \n8\nEvaluation of Voting Language Categories\n•Universal Vaccination Option \n•No Recommendation Option \n•Individual -based Decision -making Option\n (preferred first choice for Workgroup members.)\n9\nRationale for Preferring an Individual- based \nDecision -making Option (1)\n•The overwhelming majority of infants born to mothers who test \nnegative for hepatitis B surface antigen are not at high risk of being infected with the hepatitis B virus, especially in the first few months of life.\n•The 1991 recommendation was made in error.\n•Vaccine safety risks are not well understood and were never assessed appropriately.  \n•An individualized, risk -based approach is needed, with \nrecommendations tailored to risk/benefit profiles and preferences and involve informed consent. \n10\nRationale for Preferring an Individual- based \nDecision -making Option (2)\n•It has the potential to allow the parent to choose a point in time \ncloser to the onset of risky behaviors sometimes encountered in \nadolescence, and, for those who prefer to wait, the “catch -up” \nschedule could be used by those who delay until age 11.  \n•It also provides options for avoiding vaccinating in early infancy and \nadolescence when there are biological windows of vulnerability.\n•Creates an opportunity to use serology testing to determine whether additional doses of vaccine are needed for protection. \n•Could end disputes between parents of newborns, hospital staff and others who do not agree about administration of a birth dose, \nconsent, and cease to be the “gateway to vaccine hesitancy. ”\n11\nRationale for Preferring an Individual- based \nDecision -making Option (3)\n•Provides for a return of decision -making to parents in \ncollaboration with the health care provider who wants to be \nable to recommend a flexible schedule and the ability to tailor \ncare to individual needs, risks and preferences.\n•Benefits of using two months for starting HBV vaccine series\n•the additional two months of maturation, as it relates to the \nblood -brain barrier, liver, and kidney function, is desirable.  \n•is in line with the policy of other comparable countries\n•would permit the use of combination vaccines and limit the number of injections, as well as access to lower -aluminum-\ncontaining products\n. \n12\nRationale for NOT Preferring an Individual-\nbased Decision -making Option\n•Concerns about rare exposures to the hepatitis B virus that could cause an infection and a chronic infection\n \n•Concerns about acceptability to the medical and public health communities and others, media backlash, unfair treatment by medical boards\n•The system that’s in place that will be difficult to change\n•It will take too much time to counsel patients about risks and benefits, and access to educational materials isn’t obvious\n•Concerns about liability, payments, additional paperwork \n•The safety concern may be more theoretical than real\n13\nImplementation Considerations\n•PEP in births to HBsAg+ mothers:\nStrengthen maternal screening programs\nImmigrant medical examination screening\n•Delaying the timing of the first dose will allow choice of using \ndifferent vaccines, monovalent and polyvalent\n14Birth dose 2/4/6 month 4 years 8 years 12 years\nTarget groups HBsAg+ only All or high risk HHs All All All\nVaccine type Monovalent/poly\nvalent mixPolyvalent Monovalent series Monovalent Monovalent\nImplementation Considerations\n•Even under the existing universal dose policy not all babies are \nvaccinated at birth with no detectable increase in incidence of HBV infections\n•Data from the 2016 -2021 Centers for Medicare & Medicaid \nServices (CMS) Transformed Medicaid Statistical Information System (T -MSIS)1 \nComments:\n•T-MSIS Analytic Files are research- optimized collection data submitted as part of state -\nlevel Medicaid submission.\n•Includes enrollment data, demographics, and service utilization.2 \n•Hepatitis B antigen tests identified using Current Procedural Terminology [CPT] codes\n1https://www.medicaid.gov/medicaid/data -systems/macbis/transformed -medicaid -\nstatistical -information- system -t-msis/index.html\n2https://www.medicaid.gov/medicaid/data -systems/macbis/transformed -medicaid -\nstatistical -information- system -t-msis/t -msis -analytic -files\n15\nCMS Medicaid\n•Pregnancies:\n•At least one ICD -10 diagnosis code ('O80' , 'O81' , 'O82' , 'O83' , 'O84' , \n'Z370' , 'Z372' , 'Z375’) in inpatient or other service files \n•Live Born Pregnancies: \n•At least one ICD -10 Diagnosis code ('O80' , 'O81' , 'O82' , 'O83' , 'O84' , \n'Z370' , 'Z372' , 'Z375’)\n•Death not recorded during first hospitalization\n16\nTable 1: Receipt of HBV Vaccine Among Infants\nCMS Medicaid Births, 2016 -2020 \nT otal B irth%  To t a l  \nBirt h s\nT otal B irths 7,284,953 100%\nInfants Receiving First HBV Dose by 2 yrs \n  (0-730 days)6,573,976 90%\nInfants R eceiving HB V  B irth Dose   (0-30 days)5,076,855 70%\n17\nAge of First HBV Vaccination \nwithin first 730 Days\nA ge of First HBV  V accinationTo t a l  \nV accinatedTo t a l  \nV accinated \n%\nBirth Dose Received During Birth Hospitalization 4,966,112 76%\n1 - 30 days 110,743 2%\n31 - 180 days 1,289,749 20%\n181 - 365 days 145,947 2%\n365 - 730 days 61,425 1%\nInfants Receiving First Dose by 2 yrs (0 -730 days) 6,573,976 100%\n18\n•Markman, Putting Public Health Ethics Into Practice\n•Expected health benefits for the target population\n•Potential harms and burdens for all stakeholders\n•Impact on autonomy\n•Impact on equity\n•Expected efficiency\n•Ethics of Vaccination \n•Preserve Health\n•Means -end Proportionality\n•Discretion\n•Parsimony \n-Marckmann G, Schmidt H, Sofaer N, Strech D. Putting public health ethics into practice: a systematic framework. Front Public Hea lth. 2015 \nFeb 6;3:23. doi: 10.3389/fpubh.2015.00023. PMID: 25705615; PMCID: PMC4319377.Public Health and Vaccination Ethics\nACIP Childhood/Adolescent Immunization Schedule Workgroup\nVote Language, 12/3/25\nVOTE 1\n•ACIP recommends a birth dose of Hepatitis B virus (HBV) vaccine and \nHepatitis B Immunoglobulin for infants born to women who test HBsAg -\npositive. ACIP recommends individual -based decision -making, in \nconsultation with a health care provider, for parents deciding whether to give the HBV vaccine birth dose to infants born to women who are HBsAg -\nnegative or whose HBsAg status is unknown. Parents should consult with health care providers and decide when or if their child will begin the HBV vaccine series.\n1 Parents and health care providers should consider vaccine \nbenefits, vaccine risks, and infection risks. For those not receiving the HBV birth dose, it is suggested that the initial dose is administered no earlier than 2 months of age. Y/N\nVOTE 2\n•When evaluating the need for subsequent HBV vaccine dose in children, parents should consult with health care providers to determine if a post -\nvaccination anti -HBs serology testing should be offered prior to subsequent \nHBV vaccine dose administration. Serology results should determine whether the established protective anti -HBs titer threshold of ≥10 mIU /mL \nhas been achieved. The cost of this testing should be covered by insurance. Y/N\n1 Parents and health care providers should also consider whether there are risks, for example, such as a household \nmember is HBsAg -positive or when there is frequent contact with persons who have emigrated from areas where \nHepatitis B is common. \n20", "summary": "Summary of Information Childhood/Adolescent Schedule Workgroup Hepatitis B Virus Vaccine Birth Dose  December 4, 2025 Overview •Childhood/Adolescent Schedule Workgroup  •Workgroup Process •Workgroup Findings •Proposed Voting Language 1 Workgroup Members ACIP members  Kirk Milhoan, MD, PhD  Martin Kulldorff , PhD Evelyn Griffin, MDVicky Pebsworth, PhD, RN  Outside Experts Brian Morse, MD, PhD, Christine Stabell Benn, MD Ex-officio Tracy Beth Hoeg, MD, PhD 2 Policy Request Assess the use of a…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-december-04-05-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-12-04-05/04-pebsworth-hepatitis-b-508.pdf", "doc_date": "2025-12-04", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 20}
{"title": "05 santoli hepatitis b 508", "content": "VFC Resolution Update:  Hepatitis B Vaccine\nDecember 4, 2025National Center for Immunization & Respiratory Diseases\n\n•Red font in the presentation is used to indicate changes to the resolution in \ncomparison to the currently approved version.Note\n•The purpose of this resolution is to update the Recommended Vaccination \nSchedule and Intervals section to reflect updated ACIP recommendations \nabout the use of Hepatitis B vaccine.  Purpose of the Resolution\n•  All children and adolescents birth through 18 years of age.  Eligible Groups\nThe tables below list the acceptable vaccination schedules for children and \nadolescents, birth through 18 years of age.\nTable 1. InfantsRecommended Vaccination Schedule and Intervals (1) \nSingle antigen vaccine1Single -antigen1and combination \nvaccine2,3,4\nBirth \nweight Maternal \nHBsAg status Dose Age Dose Age \n≥2000 g Positive 1 B irth (≤12 hrs)11 B irth (≤12 hrs )1\n2 1-2 months12 2 months \n3 6 months 3 4 months \n4 6 months \nUnknown 1 B irth (≤12 hrs)1 1 B irth (≤12 hrs)1\n2 1-2 months12 2 months \n3 6 months 3 4 months \n4 6 months \nNegative51 2 months 1 2 months\n2 3-4 months 2 4 months \n3 6 -18 months 3 6 months \nThe tables below list the acceptable vaccination schedules for children and \nadolescents, birth through 18 years of age.\nTable 1. InfantsRecommended Vaccination Schedule and Intervals (2) \nSingle antigen vaccine1Single -antigen1and combination \nvaccine2,3,4\nBirth \nweight Maternal \nHBsAg \nstatus Dose Age Dose Age \n<2000 g Positive 1 Birth (≤12 hrs)1 1 B irth (≤12 hrs)1\n2 1 month1 2 2 months \n3 2-3 months 3 4 months \n4 6 months 4 6 months \nUnknown 1 B irth (≤12 hrs)1 1 B irth (≤12 hrs)1\n2 1 month1 2 2 months \n3 2-3 months 3 4 months \n4 6 months 4 6 months \nNegative51 2 months 1 2 months\n2 3-4 months 2 4 months \n3 6 -18 months 3 6 months \nTable Notes:\n1. Only a single antigen hepatitis B vaccine (ENGERIX -B or RECOMBIVAX HB) can be given at <6 weeks of age.  \n2. Pediarix [DTaP -IPV-HepB] is licensed for children 6 weeks through 6 years of age. For adequate immune response, the \nlast dose of hepatitis B vaccine should be given >24 weeks of age and therefore this combination vaccine should not be \nadministered as a complete primary series on an accelerated schedule at 4- week intervals for prevention of pertussis.\n3. Vaxelis [DTaP -IPV-Hib-HepB ] is licensed for children 6 weeks through 4 years of age.  For adequate immune response, \nthe last dose of hepatitis B vaccine should be given >24 weeks of age and therefore this combination vaccine should \nnot be administered as a complete primary series on an accelerated schedule at 4- week intervals for prevention of \npertussis.  \n4. Use of brand names is not meant to preclude the use of other comparable US licensed vaccines. \n5. Infants born to HBsAg -negative mothers may receive a dose of hepatitis B vaccine before two months of age  under \nindividual-based decision -making (also referred to as shared clinical decision -making), including consideration of risks \nsuch as a household member who is HBsAg positive or when there is frequent contact with persons who have \nemigrated from areas where Hepatitis B is common.  Infants vaccinated before two months of age under individual-\nbased decision -making may receive up to four doses of hepatitis B vaccine (1 dose of single antigen vaccine followed \nby 3 doses of combination vaccine). Recommended Vaccination Schedule and Intervals (3) \nTable 2. Children and AdolescentsRecommended Vaccination Schedule and Intervals (5) \nAge Schedule1,6\nChildren \n(1 through 10 years)0, 1, and 6 months2\n0, 2, and 4 months2\n0, 1, 2, and 12 months2,4\nAdolescents (11 through 18 years)0, 1, and 6 months\n2\n0, 1, and 4 months2\n0, 2, and 4 months2\n0, 12, and 24 months2\n0 and 4 -6 months3\n0, 1, 2, and 12 months2,4\n0, 7 days, 21 -30 days, 12 months5\nTable Notes: \n1.Children and adolescents not vaccinated at birth may be vaccinated according to any of the \nschedules indicated, except as noted. Selection of a schedule should consider the need to optimize \ncompliance with vaccination. \n2.Pediatric/adolescent formulation. \n3.A two -dose schedule of Recombivax -HB Adult Formulation is (10 micrograms) is licensed for \nadolescents aged 11 through 15 years.  When scheduled to receive the second dose, adolescents \naged > 15 years should be switched to a three -dose series, with doses 2 and 3 consisting of the \npediatric formulation administered on an appropriate schedule.  \n4.A four -dose schedule of Engerix B is licensed for all age groups.  \n5.Twinrix can be administered to persons 18 years of age before travel or any other potential \nexposure on an accelerated schedule at 0, 7, and 21 -30 days, followed by a dose at 12 months.   \n6.Use of brand names is not meant to preclude the use of other comparable US licensed vaccines.  Recommended Vaccination Schedule and Intervals (6) \nInterrupted schedules and minimum dosing intervals\n•When the HepB vaccine schedule is interrupted, the vaccine series does not need to be restarted.  If \nthe series is interrupted after the first dose, the second dose should be administered as soon as \npossible, and the second and third doses should be separated by an interval of at least eight weeks.  \nIf only the third dose has been delayed, it should be administered as soon as possible.  \n•The final dose of vaccine must be administered at least eight weeks after the second dose and should \nfollow the first dose by at least 16 weeks; the minimum interval between the first and second doses \nis four weeks. Inadequate doses of hepatitis B vaccine or doses received after a shorter -than \nrecommended dosing interval should be re -administered, using the correct dosage or schedule.  \n•Vaccine doses administered ≤4 days before the minimum interval or age are considered valid.  Because of the unique accelerated schedule for Twinrix , the four -day guideline does not apply to the \nfirst three doses of this vaccine when administered on a 0 day, 7 day, 21 -30 day, and 12 month \nschedule.  \n•In infants, administration of the final dose is not recommended before age 24 weeks (164 days). Recommended Vaccination Schedule and Intervals (7) \nRevaccination\nRevaccination (i.e., booster dose, challenge dose, or revaccination with a complete series) is not \ngenerally recommended for persons with a normal immune status who were vaccinated as infants, \nchildren, or adolescents. Revaccination when anti -HBs is <10 mIU/mL is recommended for the following:   \n-Infants born to HBsAg -positive mothers .  HBsAg -negative infants with anti -HBs <10 mIU/mL \nshould be re -vaccinated with a single dose of HepB vaccine and receive post vaccination serologic \ntesting 1 -2 months later.  Infants whose anti -HBs remains <10 mIU/mL following single dose \nrevaccination should receive two additional doses of HepB vaccine, followed by PVST 1 -2 months \nafter the final dose.   \n•Based on clinical circumstances or family preference, HBsAg -negative infants with anti -HBs \n<10 mIU/mL may instead be revaccinated with a second, complete 3 -dose series, followed \nby post vaccination serologic testing (PVST) performed 1 -2 months after the final dose of \nvaccine.   \n-Hemodialysis patients .  For hemodialysis patients, the need for booster doses should be assessed \nby annual anti -HBs testing.  A booster dose should be administered when anti -HBs levels decline to \n<10 mIU/mL.Recommended Vaccination Schedule and Intervals (8) \nRevaccination\n-Other immunocompromised persons .  For other immunocompromised persons (e.g., HIV -infected \npersons, hematopoietic stem -cell transplant recipients, and persons receiving chemotherapy), the \nneed for booster doses has not been determined.  When anti -HBs levels decline to <10 mIU/mL, \nannual anti -HBs testing and booster doses should be considered for persons with an ongoing risk \nfor exposure.  \n-Persons with postvaccination serologic testing results that do not demonstrate protection . This \nincludes children and adolescents through age 18 years who are chronic hemodialysis patients, \nHIV-infected, otherwise immunocompromised (e.g., hematopoietic stem -cell transplant recipients \nor persons receiving chemotherapy), or sex partners of HBsAg -positive persons. Persons in these \ngroups found to have anti -HBs concentrations of <10 mIU/mL after the primary vaccine series \nshould be revaccinated.  Recommended Vaccination Schedule and Intervals (9) \nRecommended dosage\nRefer to package inserts available at:  Vaccines Licensed for Use in the United \nStates | FDA\nContraindications and Precautions\nContraindications can be found in the package inserts available at: Vaccines \nLicensed for Use in the United States | FDADosage, Contraindications, Precautions\n•[If an ACIP recommendation or notice regarding hepatitis B vaccination \nimmunization is published within 6 months following this resolution, the \nrelevant language above (except in the eligible groups sections) will be \nreplaced with the language in the recommendation and incorporated by \nreference to the publication URL.]Statement Regarding Update Based on Published Documents", "summary": "VFC Resolution Update:  Hepatitis B Vaccine December 4, 2025National Center for Immunization & Respiratory Diseases  •Red font in the presentation is used to indicate changes to the resolution in  comparison to the currently approved version.Note •The purpose of this resolution is to update the Recommended Vaccination  Schedule and Intervals section to reflect updated ACIP recommendations  about the use of Hepatitis B vaccine.  Purpose of the Resolution •  All children and adolescents birth…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-december-04-05-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-12-04-05/05-santoli-hepatitis-b-508.pdf", "doc_date": "2025-12-04", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 14}
{"title": "02 johnson coverage implications", "content": "Centers for Medicare & Medicaid Services\nOverview of Vaccine Coverage\nDecember 2025\n1\nMedicaid and CHIP\n•Coverage of vaccines is anchored to ACIP recommendations, and the \nadult/pediatric vaccine schedules, which is based on those recommendations. \n•State Medicaid and Children’s Health Insurance Programs (CHIP) are required to \ncover all vaccines recommended by CDC/ACIP that are included on the \nadult/pediatric immunization schedules without cost sharing for most \nbeneficiaries, including children and adults.*\n•Recommendations included on the pediatric/adult immunization schedules that \nrefer to shared clinical decision making, also known as individual -based decision \nmaking, are mandatorily covered in both Medicaid and CHIP .\n•The Vaccines For Children (VFC) program is a vaccine distribution program \noverseen by CDC that provides federally purchased vaccines to children through \nage 18 who are either enrolled in Medicaid, uninsured, underinsured, or \nAmerican Indian/Alaska Native. Each state runs a VFC program according to CDC \nguidelines, typically through the state health department, and makes state \ncoverage decisions. \n* Mandatory Medicaid vaccination coverage varies between adults and children, see the coverage chart on slide 4 for more info rmation. \n2\nMedicaid and CHIP (continued)\n•States have flexibility to determine Medicaid/CHIP coverage beyond mandatory \ncoverage anchored to the ACIP/CDC recommendations and the pediatric and adult \nimmunization schedules. Therefore, any recommendation that is not on the pediatric \nvaccine schedule or any recommendation that narrows the criteria will lead to variable \ncoverage across state Medicaid & CHIP programs.\n•In Medicaid, through Early and Periodic Screening, Diagnostic, and Treatment (EPSDT) \nrequirements, coverage for individuals up to age 21 could include additional \nvaccinations beyond what is included on the vaccine schedule based on the state’s \nmedical necessity criteria. In CHIP , states have the flexibility to choose to cover vaccines \nbeyond what is included in the immunization schedule.\n•If states opt to provide expanded vaccine coverage, they will receive federal match for \nthe full scope of coverage. States may not need approval from CMS to provide coverage \nbeyond the ACIP recommendation as that level of detail is not required in the Medicaid \n& CHIP state plans. \n3\nMedicaid and CHIP (continued)\n4Population Is coverage of vaccines and their administration mandatory?\nAdult Medicaid Full Coverage/Full \nBenefit Enrollees YES, for all categories of ACIP recommendations .\nAdults Enrolled in Alternative \nBenefit Plans (typically adults \nenrolled in the Medicaid expansion)YES, for all routine ACIP recommendations (those on the adult/pediatric immunization \nschedule) .  States that align ABP coverage with state plan coverage will need to cover all \nACIP recommended vaccinations per the IRA coverage requirements.\nChild Medicaid Full Coverage/Full \nBenefit Enrollees Aged 18 and \nYounger YES, for all vaccines on the CDC/ACIP pediatric schedule and those vaccinations determined \nto be medically necessary as established by the state. Therefore, any recommendation that \nis not on the pediatric vaccine schedule or any recommendation that narrows the criteria \nwill lead to variable coverage across state Medicaid & CHIP programs.\nChild Medicaid Full Coverage/Full \nBenefit Enrollees Aged 19 and OlderYES, for all categories of ACIP recommendations.\nCHIP Enrollees YES, for all categories of ACIP recommendations . \nPrivate / Employer Sponsored Plans\n•Non -grandfathered employer -sponsored plans and non -grandfathered group and \nindividual health insurance coverage are required to cover all ACIP -recommended \nvaccines for routine use without cost sharing. \noThis includes recommended vaccines on the pediatric vaccine schedule. \n•With respect to employer -sponsored and individual health insurance coverage (as \nopposed to self -insured employer -sponsored plans governed by ERISA), states may \nimpose benefit mandates, including vaccination mandates, that are more expansive \nthan Federal requirements.\n•Plans and issuers are required to continue to cover the vaccine in a manner \nconsistent with the current recommendation for the duration of a plan or policy year \nbefore the applicable plan or policy year of the new recommendation, unless doing so \nwould pose a significant safety concern.\n5", "summary": "Centers for Medicare & Medicaid Services Overview of Vaccine Coverage December 2025 1 Medicaid and CHIP •Coverage of vaccines is anchored to ACIP recommendations, and the  adult/pediatric vaccine schedules, which is based on those recommendations.  •State Medicaid and Children’s Health Insurance Programs (CHIP) are required to  cover all vaccines recommended by CDC/ACIP that are included on the  adult/pediatric immunization schedules without cost sharing for most  beneficiaries, including…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-december-04-05-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-12-04-05/02-johnson-coverage-implications.pdf", "doc_date": "2025-12-04", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 5}
{"title": "01 siri child imz schedule 508", "content": "Development of the U.S. Childhood Vaccine Schedule\nAaron SiriACIP Meeting, December 5, 2025With A Focus on Suggested Improvements\nDisclosuresManaging Partner of Siri & Glimstad LLP with 100+ professionals who handle civil rights, exemptions, immigration, employment, and injury claims related to vaccination. Author of Vaccines, Amen: The Religion of Vaccines.\n2\n\nGrowth of U.S. Childhood Vaccine Schedule\nGrowth of U.S. Vaccine Schedule\n4Source:https://www.cdc.gov/vaccines/hcp/imz-schedules/resources.html \n1983 U.S. Vaccine Schedule\n\nGrowth of U.S. Vaccine Schedule2025 U.S. Vaccine Schedule\n5\nSource: https://www.cdc.gov/vaccines/hcp/imz-schedules/downloads/child/0-18yrs-child-combined-schedule.pdf\n\nGrowth of U.S. Vaccine Schedule1983 v. 2025 U.S. Childhood Vaccine Schedule\n6Reflects: stand-alone routine vaccines given at earliest recommended age; and 3-dose RV, 4-dose Hib, and 2-dose HPV series. Sources: https://www.cdc.gov/vaccines/hcp/imz-schedules/resources.html; https://www.cdc.gov/vaccines/hcp/imz-schedules/child-adolescent-age.html; https://www.cdc.gov/vaccines-pregnancy/hcp/vaccination-guidelines/index.html   Routine Vaccines: In Utero to 18 Years\nVaccines given<12 months of ageVaccines given > 12 months of age19832025DTP (2 Months)OPV (2 Months)DTP (4 Months)OPV (4 Months)DTP (6 Months)MMR (15 Months)DTP (18 Months)OPV (18 Months)DTP (4 Years)OPV (4 Years)Td (14 Years)IPV (6 Months)Hep B (6 Months)Flu (6 Months)Flu (7 Months)Hib (12 Months)PCV (12 Months)Hep A (12 Months)VAR (12 Months)MMR (12 Months)DTaP (15 Months)Hep A (18 Months)Flu (2 Years)Flu (3 YearsDTaP (4 Years)IPV (4 Years)Flu (4 Years)MMR (4 Years)VAR (4 Years)Flu (5 Years)Flu (6 Years)Flu (7 Years)Flu (8 Years)Flu (9 Years)Flu (10 Years)Tdap (11 Years)HPV (11 Years)Flu (11 Years)HPV (11 Years)MenACWY (11 Years)Flu (12 Years)Flu (13 Years)Flu (14 Years)Flu (15 Years)MenACWY (16 Years)Flu (16 Years)Flu (17 Years)Flu (18 Years)TdaP (In Utero)Flu (In Utero)RSV (In Utero or Birth)Hep B (Birth)Hep B (1 Month)RV (2 Months)DTap (2 Months)Hib (2 Months)PCV15 (2 Months)IPV (2 Months)RV (4 Months)DTap (4 Months)Hib (4 Months)IPV (4 Months)PCV15 (4 Months)RV (6 Months)DTap (6 Months)Hib (6 Months)PCV15 (6 Months)\nGrowth of U.S. Vaccine Schedule1983 v. 2025 U.S. Childhood Vaccine Schedule\n7Routine + Shared Decision-Making Vaccines (Covid-19 and MenB)\nReflects: stand-alone routine vaccines given at earliest recommended age; and 3-dose RV, 4-dose Hib, 2-dose HPV, and 3-dose Covid-19 series. Sources: https://www.cdc.gov/vaccines/hcp/imz-schedules/resources.html; https://www.cdc.gov/vaccines/hcp/imz-schedules/child-adolescent-age.html; https://www.cdc.gov/vaccines-pregnancy/hcp/vaccination-guidelines/index.html   Vaccines given<12 months of ageVaccines given > 12 months of age19832025DTP (2 Months)OPV (2 Months)DTP (4 Months)OPV (4 Months)DTP (6 Months)MMR (15 Months)DTP (18 Months)OPV (18 Months)DTP (4 Years)OPV (4 Years)Td (14 Years)Covid-19 (11 Years)Flu (12 Years)Covid-19 (12 Years)Flu (13 Years)Covid-19 (13 Years)Flu (14 Years)Covid-19 (14 Years)Flu (15 Years)Covid-19 (15 Years)MenB (16 Years pt.1)MenACWY (16 Years)Flu (16 Years)MenB (16 Years pt.2)Covid-19 (16 Years)Flu (17 Years)Covid-19 (17 Years)Flu (18 Years)Covid-19 (18 Years)TdaP (In Utero)Flu (In Utero)RSV (In Utero or Birth)Hep B (Birth)Hep B (1 Month)RV (2 Months)DTap (2 Months)Hib (2 Months)PCV15 (2 Months)IPV (2 Months)RV (4 Months)DTap (4 Months)Hib (4 Months)IPV (4 Months)PCV15 (4 Months)RV (6 Months)DTap (6 Months)Hib (6 Months)PCV15 (6 Months)IPV (6 Months)Hep B (6 Months)Flu (6 Months)Covid-19 (6 Months)Flu (7 Months)Covid-19 (7 Months)Covid-19 (9 Months)Hib (12 Months)PCV (12 Months)Hep A (12 Months)VAR (12 Months)MMR (12 Months)DTaP (15 Months)Hep A (18 Months)Flu (2 Years)Covid-19 (2 Years)Flu (3 YearsCovid-19 (3 Years)DTaP (4 Years)IPV (4 Years)Flu (4 Years)MMR (4 Years)VAR (4 Years)Covid-19 (4Years)Flu (5 Years)Covid-19 (5 Years)Flu (6 Years)Covid-19 (6 Years)Flu (7 Years)Covid-19 (7 Years)Flu (8 Years)Covid-19 (8 Years)Flu (9 Years)Covid-19 (9Years)Flu (10 Years)Covid-19 (10 Years)Tdap (11 Years)HPV (11 Years)Flu (11 Years)HPV (11 Years)MenACWY (11 Years)\nGrowth of U.S. Vaccine Schedule\n1983 v. 2025 U.S. Vaccine Schedules\n8Routine Vaccines: In Utero To 12 Months\nReflects stand-alone routine vaccines given at earliest recommended age; and 3-dose RV and 4-dose Hib series. Sources:https://www.cdc.gov/vaccines/hcp/imz-schedules/resources.html; https://www.cdc.gov/vaccines/hcp/imz-schedules/child-adolescent-age.html; https://www.cdc.gov/vaccines-pregnancy/hcp/vaccination-guidelines/index.html   \nGrowth of U.S. Vaccine Schedule2025 U.S. Vaccine Schedule\n9All data reflects rates at approximately 2 years of age except for Tdap, HPV, and MenACWY which reflect the rate for ages 13 to 17.  Sources: https://web.archive.org/web/20190618125412https:/www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendices/e/coverage-levels.pdf; 1983 IIV uptake is an estimate; https://www.cdc.gov/mmwr/volumes/73/wr/mm7338a3.htm; https://www.cdc.gov/mmwr/volumes/70/wr/mm7035a1.htm?s_cid=mm7035a1_wRoutine Vaccine Coverage: United States 1983 v. 20201983202066%65%57%3%0%0%0%0%0%0%0%0%MMRDTPOPVIIVHepBHibPCVRVVARHepATdapHPV0%MenACWY3+ Doses1+ Doses3+ Doses94%92%93%63%93%94%\nDTaPMMRIPVIIVHepBHibPCVRVVARHepATdapHPVMenACWY1+ Doses3+ Doses3+ Doses2+ Doses3+ Doses2+ Doses93%3+ Doses77%2+ Doses91%1+ Doses88%1+ Doses90%1+ Doses75%1+ Doses89%1+ Doses\nPre-Licensure Safety: U.S. Childhood Vaccine Schedule\nPre-Licensure Safety of the U.S. Vaccine ScheduleImportance of Clinical Trials\n11* Stand-alone vaccines for children, excluding influenza; IPOL date is an estimate; DTP date uncertain. Source of data: see accompanying memorandum.Vaccine*Year Licensed for ChildrenYear ACIP Recommended for Routine Use in Children [Earlier Non-Routine Use]Days Between Licensure & RecommendationDTP (various)M-M-R-II (Merck)MenomuneRecombivax HB (Merck)Engerix-B (GSK)PedvaxHIB (Merck)Ipol (Sanofi)ActHIB (Sanofi)Varivax (Merck)Havrix (GSK)Vaqta (Merck)Infanrix (GSK)Prevnar 7*19781981198619891989199019931995199519961997200019661978199119911990 199719931996 2006 200619972000*49 days 1948 days 816 days133 days 2580 days24 days294 days 4104 days 3703 days73 days-1 days[1985][1987][1990][1994][1996][1996][1264][331][192][1691][674][273]Vaccine*Year Licensed for ChildrenYear ACIP Recommended for Routine Use in Children [Earlier Non-Routine Use]Days Between Licensure & RecommendationDaptacel (Sanofi)Boostrix (GSK)Adacel (Sanofi)Menactra (Sanofi)Gardasil (Merck)Hiberix (GSK)Prevnar 13 (Pfizer)Menveo (GSK)Gardasil-9MenQuadfi (Sanofi)Vaxneuvance (Merck)Priorix (GSK)Prevnar 20 (Pfizer)2002200520052005200620092010201020142020202220222023200220052005200520062009201020102015202020222022202352 days24 days20 days27 days21 days30 days0 days19 days78 days62 days5 days17 days56 daysCurrent routine vaccine recommended for children.Previously recommended for children and used as control to license currently recommended vaccine.\nPre-Licensure Safety of the U.S. Vaccine ScheduleQuality of Trials Crucial\n12Source:  * https://www.fda.gov/media/130326/download  † https://jamanetwork.com/journals/jamapediatrics/fullarticle/2714387 ControlSafety Review PeriodPowerA placebo (defined by FDA as “inert substances”*) or another vaccine for same indication that was properly trialed prior to licensure.To “provide complete safety data across all critical periods of growth and development,” as compared to trials for adults, “data on drug efficacy and safety in children may require an additional 6 years.” JAMA Pediatrics, author affiliations Office of Pediatric Therapeutics, FDA, and Duke Clinical Research Institute.†Enough participants to assess if benefits outweigh risks.Critical to avoid bias.Randomized and Blinded\nPre-Licensure Safety of the U.S. Vaccine ScheduleDrug Trials\n13Trials Relied Upon to License Pfizer’s Top 4 Most Profitable Drugs*\n* As of 2019. Sources: https://moneyinc.com/the-five-highest-selling-pfizer-drugs-of-all-time/; https://www.fda.gov/drugs/development-approval-process-drugs/drug-approvals-and-databases  Eliquis 7.4 Years PlaceboLipitor4.9 YearsPlaceboLyrica2 YearsPlaceboDRUG SAFETY REVIEW CONTROL Enbrel 6.6 Years Placebo\nPre-Licensure Safety of the U.S. Vaccine ScheduleChildhood Vaccine Trials\n“[W]idespread vaccine hesitancy observed during the Covid-19 pandemic suggests that the public is no longer satisfied with the traditional safety goal of simply detecting and quantifying the associated risks after a vaccine has been authorized for use.”“Postauthorization studies are needed to fully characterize the safety profile of a new vaccine, since prelicensure clinical trials have limited sample sizes, follow-up durations, and population heterogeneity.”14\nSource: https://www.nejm.org/doi/full/10.1056/NEJMp2402379 \nPre-Licensure Safety of the U.S. Vaccine ScheduleControls Routine Vaccines: Birth to 6 Months\n15Lists stand-alone routine vaccines. Some DTP trials use other DTP vaccines as a control but none licensed based on placebo-controlled trial. See supporting memorandum for sources.Vaccine TypeVaccineControlPlacebo?Hep BEngerix-B (GSK)No controlRecombivax HB (Merck)No controlDTaPInfanrix (GSK)DTP No controlDaptacel (Sanofi)DTP No controlHibActHIB (Sanofi)Hep B    No controlHiberix (GSK)ActHIB     Hep B        No ControlPedvaxHIB (Merck)Lyophilized PedvaxHIB            Injection of lactose, aluminum adjuvant, and thimerosalPCVVaxneuvance (Merck)Prevnar 13            Prevnar 7   Investigational vaccinePrevnar 20 (Pfizer)Prevnar 13            Prevnar 7   Investigational vaccineIPVIpol (Sanofi)No controlIIVVariousNo placebo control – see memorandumNONONONONONONONONONONO\nPre-Licensure Safety of the U.S. Vaccine ScheduleControls Routine Vaccines: 7+ Months of Age\n16Lists stand-alone routine vaccines. See supporting memorandum for sources.Vaccine TypeVaccineControlPlacebo?MMRM-M-R-II (Merck)No controlPriorix (GSK)M-M-R-II            No controlVaricellaxVarivax (Merck)Injection of 45mg of neomycin per ml (465 subjects)Havrix (GSK)Engerix-B            No controlHep AVaqta (Merck)Injection of AAHS and thimerosalBoostrix (GSK)Decavac        No controlAdacel (Sanofi)Decavac        No controlTdapGardisil-9 (Merck)Gardasil or Placebo+Gardasil (3 doses) (306 subjects)HPVMenveo (GSK)Menactra            Menomune             No controlMenACWYMenQuadfi (Sanofi)Menveo            Menactra             Menomune or Menactra            No controlNONONONONONONONONONOInjection of AAHS or Gardasil carriersolution (yeast protein...) (320 subjects)\nPre-Licensure Safety of the U.S. Vaccine ScheduleSafety DurationsSafety in childhood trials is typically reviewed for 6 months or less after injection—often only days or weeks.\n17Stand-alone routine infant vaccines. See supporting memorandum for sources.Vaccine TypeVaccineSolicited ReactionsUnsolicited ReactionsHep BRecombivax HB (Merck)5 daysEngerix-B (GSK)4 daysHibActHIB (Sanofi)3 daysPedvaxHIB (Merck)3 daysDTaPHiberix (GSK)4 daysInfanrix (GSK)8 daysDaptacel (Sanofi)14 daysIPVIPOL (Sanofi)3 daysVaxneuvance (Merck)14 daysPrevnar 20 (Pfizer)7 daysDuration of Safety Review After Injection\nPCV5 days4 days30 days3 days31 days30 days6 months3 days6 months6 months\nPre-Licensure Safety of the U.S. Vaccine ScheduleStatistical PowerInsufficient number of children in trials to assess if benefits outweigh risks.\n18See supporting memorandum for discussion and sources. \nExample: First vaccine on the schedule, Hep B\nPre-Licensure Safety of the U.S. Vaccine ScheduleExample: Hep B Vaccines\n19\nSources: https://www.fda.gov/vaccines-blood-biologics/vaccines/recombivax-hb; https://www.fda.gov/vaccines-blood-biologics/vaccines/engerix-b \n\nPre-Licensure Safety of the U.S. Vaccine ScheduleExample: Hep B Vaccines\n20Source: https://www.cdc.gov/mmwr/preview/mmwrhtml/00033405.htm     \n295281229438142528292Cited Articles Involving Children Receiving Recombivax, Engerix-B, or Other Recombinant DNA VaccinePMIDSafety Monitoring After InjectionNumber of ChildrenFunding7 days5 days3 days122794,250Merck conducted and fundedIMerck conducted and fundedGSK funded\nPre-Licensure Safety of the U.S. Vaccine ScheduleExample: Hep B Vaccines\n21Source: https://www.cdc.gov/acip/downloads/slides-2025-09-18-19/02-langer-hep-b-508.pdf; https://www.nationalacademies.org/read/13164/chapter/2#2   \nACIP Presentation:September 18, 2025Institute of Medicine FindingsAdverse Event – Hep B VaccineAnaphylaxisEncephalitisEncephalopathySeizuresAcute Disseminated EncephalomyelitisTransverse MyelitisOptic NeuritisNeuromyelitis OpticaMultiple Sclerosis OnsetMultiple Sclerosis RelapseFirst Demyelinating EventGuillain-Barre SyndromeCIDPSupportsInadequateInadequateInadequateInadequateInadequateInadequateInadequateInadequateInadequateInadequateInadequateInadequateBrachial NeuritisErythema NodosumSystemic Lupus ErythematosusVasculitisPolyarteritis NodosaPsoriatic ArthritisReactive ArthritisInadequateRheumatoid ArthiritisJuvenile Idiopathic ArthiritisType 1 DiabetesFibromyalgiaInadequateInadequateInadequateInadequateInadequateInadequateInadequateInadequateInadequateInadequateInadequateInadequateAdverse Event – Hep B VaccineThe Evidence on Causation:Supports, Rejects, or InadequateThe Evidence on Causation:Supports, Rejects, or Inadequate\nPre-Licensure Safety of the U.S. Vaccine ScheduleExample: PCV VaccinesFirst Licensed PCV Vaccine: PCV-7Licensed: February 17, 2000Control: “Investigational meningococcal group C conjugate vaccine”Safety review: 30 days (emergency room), 60 days (hospitalizations), longer (select conditions)\n22Source: https://stacks.cdc.gov/view/cdc/76558; https://jamanetwork.com/journals/jama/fullarticle/199581  \n“Prior to licensure … the control group in the main study received another experimental vaccine, rather than a placebo. If both vaccines provoked similar adverse effects, little or no difference between the 2 groups might have been evident.” Also noting the “limited sample sizes of trials.”\n__________________________________________________________________________________________ACIP Added to Schedule: February 16, 2000\nPre-Licensure Safety of the U.S. Vaccine ScheduleExample: PCV VaccinesSecond Licensed PCV Vaccine: PCV-13\n23Source: https://www.fda.gov/media/107657/download; https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5911a1.htm; https://www.fda.gov/safety/reporting-serious-problems-fda/what-serious-adverse-event   \n•Death•Life-threatening•Hospitalization•Disability or Permanent Damage•Congenital Anomaly/Birth Defect•Required Intervention to Prevent Permanent Impairment•Require Medical or Surgical Intervention to Prevent an Outcome Above\nLicensed: February 24, 2010ACIP Added to Schedule: February 24, 2010\nPre-Licensure Safety of the U.S. Vaccine ScheduleExample: PCV VaccinesThird Licensed PCV Vaccine: PCV-15Licensed: June 17, 2022ACIP Added to Schedule: June 22, 2022\n24Source: https://www.fda.gov/media/150819/download\n\nPre-Licensure Safety of the U.S. Vaccine ScheduleExample: PCV Vaccines Recap\n25Days in each box reflects period between licensure & ACIP addition to scheduleInvestigationalVaccinePrevnar 7-1 DAYSPrevnar 130 DAYSVaxneuvance5 DAYSPrevnar 2056 DAYS\nPre-Licensure Safety of the U.S. Vaccine ScheduleFinal Example: DTaP Vaccines2014 SAGE Systematic Review“The majority of studies indicated a deleterious effect of DTP on mortality.”26Source: https://terrance.who.int/mediacentre/data/sage/SAGE_Docs_Ppt_Apr2014/9_session_non-specific_vaccine_effects/Apr2014_session9_epidemiologic_review.pdfDays in each box reflects period between licensure & ACIP addition to scheduleDTPInfanrixDaptacel73 DAYS52 DAYS\nPre-Licensure Safety of the U.S. Vaccine ScheduleFinal Example: DTaP Vaccines\n27Source: https://pubmed.ncbi.nlm.nih.gov/28188123/. See memorandum for discussion and additional sources. \n\nPre-Licensure Safety of the U.S. Vaccine ScheduleNon-Routine VaccinesExample: Dengue VaccineClinical Trial:•Safety Review: 6 Years for severe dengue•Control: Placebo•Size: 30,000+Findings:•Age <6: increased risk of severe harm and death from the vaccine•Age >6 and never had dengue: increased risk of severe harm and death from the vaccine28Source: https://www.fda.gov/media/125481/download; https://www.fda.gov/media/124379/download \nPre-Licensure Safety of the U.S. Vaccine ScheduleDrug Trials v. Vaccine Trials\n29Trials Relied Upon to License Pfizer’s Top 4 Most Profitable Drugs*\n* As of 2019. Sources: https://moneyinc.com/the-five-highest-selling-pfizer-drugs-of-all-time/; https://www.fda.gov/vaccines-blood-biologics/vaccines/vaccines-licensed-use-united-statesEliquis 7.4 Years PlaceboLipitor4.9 YearsPlaceboLyrica2 YearsPlaceboDRUG SAFETY REVIEW CONTROL Enbrel 6.6 Years Placebo\nPre-Licensure Safety of the U.S. Vaccine ScheduleImpact of Immunity on Market Forces\n30\nSee supporting memorandum  \nPre-Licensure Safety of the U.S. Vaccine ScheduleEthics Of Relying On Improperly Controlled Trials\n31Source: https://pmc.ncbi.nlm.nih.gov/articles/PMC1113953/“In some trials placebos were omitted on ethical grounds. This is illogical because studies destined to produce unreliable results should themselves be considered unethical.”British Medical JournalAuthor affiliations: University of Oxford, Oxford Radcliffe Hospital, Radcliffe Infirmary, and Geneva University Hospital\nPre-Licensure Safety of the U.S. Vaccine ScheduleRevisit ACIP Recommendations\n32Robust clinical trial data should support the safety of each recommendation.\nPost-Licensure Safety: U.S. Childhood Vaccine Schedule\nPost-Licensure Safety of the U.S. Vaccine Schedule1991 IOM report: Adverse Effects of Pertussis and Rubella Vaccines \nSource: https://www.nationalacademies.org/publications/181534Vaccine TypePertussis1. Acute encephalopathy  2. Shock and “unusual  shock-like state”  3. Anaphylaxis 4. Protracted, inconsolable  crying1. Autism  2. Aseptic meningitis 3. Chronic neurologic damage 4. Erythema multiforme or  other rash 5. Guillain-Barre syndrome 6. Hemolytic anemia 7. Juvenile diabetes 8. Learning disabilities and  attention-deficit disorder 9. Peripheral mononeuropathy 10. Thrombocytopenia 11. Radiculoneuritis and  other neuropathies 12. Thrombocytopenic purpuraRubella5. Chronic arthritis 6. Acute arthritis1. Infantile spasms 2. Hypsarrythmia 3. Reye syndrome; 4. Sudden infant death syndromeThe EvidenceFavors Rejectinga Causal RelationshipFavors Accepting or Convincingly Supports a Causal RelationshipIs Inadequate to Accept or Rejecta Causal Relationship\nPost-Licensure Safety of the U.S. Vaccine Schedule1994 IOM report: Adverse Events Associated with Childhood Vaccines \nSource: https://www.nationalacademies.org/publications/213835“The lack of adequate data regarding many of the adverse events under study was of major concern to the committee.Presentations at public meetings indicated that many parents and physicians share this concern.”DT/Td/TMeaslesMumpsOPV/IPV Hepatitis B H. influenzaetype (Hib) Vaccine Type1. Encephalopathy  2. Infantile spasms (DT only) 3. Death from SIDS (DT only)The EvidenceFavors Rejectinga Causal RelationshipFavors Accepting or Convincingly Supports a Causal RelationshipIs Inadequate to Accept or Rejecta Causal Relationship1. Guillain-Barre syndrome 2. Brachial neuritis 3. Anaphylaxis4. Anaphylaxis 5. Thrombocytopenia (MMR) 6. Anaphylaxis (MMR)7. Death from measles  vaccine-strain viral infection1. Residual seizure disorder than infantile spasms 2. Demyelinating diseases of the central nervous system 3. Mononeuropathy4. Arthritis5. Erythema maltiforme6. Encephalopathy 7. Subacute sclerosing panencephalitis   central nervous system 8. Residual seizure9. Sensorineural deafness (MMR) 10. Optic neuritis11. Transverse-myelitis12. Guillain-Barre syndrome 13. Thrombocytopenia14. Insulin-dependent diabetes mellitus15. Neuropathy16. Residual seizure disorder 17. Encephalopathy 18. Aseptic meningitis  19. Sensorineural deafness (MMR) 20. Insulin-dependent diabetes mellitus21. Sterility22. Thrombocytopenia23. Anaphylaxis24. Encephalopathy25. Subacute sclerosing panencephalitis26. Residual seizure 27. Sensorineural deafness (MMR)  28. Optic neuritis29. Transverse-myelitis30. Guillain-Barre syndrome31. Thrombocytopenia32. Insulin-dependent diabetes mellitus8. Guillain-Barre syndrome  (OPV)  9. Poliomyelitis in recipient or  contact (OPV)  10. Death from polio 11. Anaphylaxis33. Guillain-Barre syndrome34. Demyelinating diseases of the central nervous system35. Arthritis36. Death from SIDS12. Early-onset H. influenzae b  disease in children age 18  months or older who receive  their first Hib immunization  with unconjugated PRP  vaccine37. Guillain-Barre syndrome38. Transverse myelitis39. Thrombocytopenia40. Anaphylaxis41. Death from SIDS4. Early onset H. influenzae  disease (conjugate vaccines)\nPost-Licensure Safety of the U.S. Vaccine Schedule2012 IOM report: Adverse Effects of Vaccines: Evidence and Causality \nSource: https://www.nationalacademies.org/projects/PHPH-H-08-17-A/publication/13164 362624232312 108  8Hep BDTaP/Tdap/TD/TdInfluenzaMMRHPVVaricellaHep AMeningococcal01220 0 0011251501Vaccine TypeThe EvidenceFavors Rejectinga Causal RelationshipFavors Accepting or Convincingly Supports a Causal RelationshipIs Inadequate to Accept or Rejecta Causal Relationship\nTotal516134\nPost-Licensure Safety of the U.S. Vaccine ScheduleCombined Results of the IOM Reports\nSource: https://www.nationalacademies.org/publications/1815; https://www.nationalacademies.org/publications/2138; https://www.nationalacademies.org/projects/PHPH-H-08-17-A/publication/13164 374339302312109855MMRDTaP/Tdap/TD/TdHep BInfluenzaHPVVaricellaHep AMeningococcalHibOPV/IPV28020 0 001011822150113Vaccine TypeThe EvidenceFavors Rejectinga Causal RelationshipFavors Accepting or Convincingly Supports a Causal RelationshipIs Inadequate to Accept or Rejecta Causal Relationship\nTotal1334183\nPost-Licensure Safety of the U.S. Vaccine SchedulePost-Licensure Vaccine Safety Funding Insufficient\n“It is critical to examine adverse events following immunization (AEFIs) that have not been detected in clinical trials, to ascertain whether they are causally or coincidentally related to vaccination.”“Although the ACIP acknowledges the need, there are currently no resources earmarked for postauthorization safety studies beyond annual appropriations, which must be approved by Congress each year.” “[T]he budget for vaccine-safety monitoring at the CDC (which is responsible for the majority of U.S. federal efforts) has remained stagnant … at about $20 million per year” which is an “inadequate level of funding.”Source: https://www.nejm.org/doi/full/10.1056/NEJMp2402379  38\nPost-Licensure Safety of the U.S. Vaccine ScheduleInjury Claimed To Have Been Most Thoroughly Studied\nSource: https://www.congress.gov/99/statute/STATUTE-100/STATUTE-100-Pg3743.pdf\n39\nPost-Licensure Safety of the U.S. Vaccine Schedule\nSource: https://doi.org/10.17226/1815Injury Claimed To Have Been Most Thoroughly Studied\n40\nPost-Licensure Safety of the U.S. Vaccine Schedule\nSource: https://doi.org/10.17226/13164 \nInjury Claimed To Have Been Most Thoroughly Studied\n41\nPost-Licensure Safety of the U.S. Vaccine Schedule\nSee accompanying memorandum for source and discussion.\nInjury Claimed To Have Been Most Thoroughly Studied\n42\nPost-Licensure Safety of the U.S. Vaccine ScheduleInjury claimed to have been most thoroughly studied\nSource: https://ecf.nysd.uscourts.gov/doc1/127126484251\n18 involving thimerosal and/or MMR1  involving antigen (not vaccine) exposure1 involving MMR, thimerosal, and DTaP43\nPost-Licensure Safety of the U.S. Vaccine ScheduleInjury claimed to have been most thoroughly studied\n44\nSource: https://www.cdc.gov/vaccine-safety/about/autism.html \nPost-Licensure Safety of the U.S. Vaccine ScheduleAdverse Reactions Manufacturers Have a Basis to Believe Are Causally RelatedFederal Law: 21 C.F.R. §201.57Package inserts for vaccines should include “only those adverse events for which there is some basis to believe there is a causal relationship between the drug and the occurrence of the adverse event.”\nSource: https://www.fda.gov/media/72139/download FDA: Guidance for Industry: Adverse Reaction Section for Labeling for Drugs and Biological Products – Content and Format: “For purposes of prescription drug labeling and this guidance, an adverse reaction … does not include all adverse events observed during use of a drug, only those for which there is some basis to believe there is a causal relationship between the drug and the occurrence of the adverse event.” 45\nPost-Licensure Safety of the U.S. Vaccine ScheduleImportance of Unexposed GroupCDC Manual for the Surveillance of Vaccine-Preventable Diseases“Because … there is a lack of an unvaccinated group for comparison in VAERS…, reports to VAERS are useful for generating hypotheses, but studies with vaccinated and unvaccinated subjects are necessary to confirm any hypotheses.”* * *Studies finding safety concerns that lack an unexposed group are often discarded. Example: DTaP and autism study. Sources: https://www.cdc.gov/surv-manual/php/table-of-contents/chapter-21-vaers.html46\nPost-Licensure Safety of the U.S. Vaccine Schedule2013 IOM Vaccine Schedule Safety Review“[N]o study … compared the differences in health outcomes … between entirely unimmunized populations of children and fully immunized children. Experts who addressed the committee pointed not to a body of evidence that had been overlooked but rather to the fact that existing research has not been designed to test the entire immunization schedule. …[Also,] studies designed to examine the long-term effects of the cumulative number of vaccines or other aspects of the immunization schedule have not been conducted.”The IOM committee explained “there is no evidence that the schedule is not safe.”Source: https://www.ncbi.nlm.nih.gov/books/NBK206948/  The Childhood Immunization Schedule and Safety\n47\nPost-Licensure Safety of the U.S. Vaccine ScheduleUnvaccinated Children in the U.S.\n* National Immunization Survey-Child estimates 1.2% of 2-year-olds in the U.S. are unvaccinated. Based on exemption rate data for school age children, at least 1% appear to remain unvaccinated.https://www.cdc.gov/mmwr/volumes/73/wr/pdfs/mm7341a3-H.pdf; https://www.cdc.gov/schoolvaxview/data/index.html 48Age(s)Unvaccinated(no vaccines) est.2 Years of Age2-17 Years of Age45,300658,000\nPost-Licensure Safety of the U.S. Vaccine ScheduleCDC Surveillance Systems\nSee supporting memorandum for sources and discussion. * https://www.cdc.gov/vaccine-safety/media/pdfs/white-paper-safety-508.pdf   49“The current safety surveillance systems such as the VSD … already have extensive systems in place to assess short-term outcomes … [despite the fact] the childhood immunization schedule is essentially a long-term exposure, occurring over 18 to 24 months, [and hence] long-term adverse events may be more biologically plausible than short-term events.” – CDC*CDCStudy Vaccinated v. UnvaccinatedPopulationsVSDNoteVAERSV-SafeCISANONONONOEstimated to include >20,000 unvaccinated children. Deidentified data not shared with public.CDC has refused to automate capture and submission of VAERS reports.Automated but fails to list reactions of interest.Not useful for assessing safety at a population level.\nPost-Licensure Safety of the U.S. Vaccine ScheduleStudies With Unvaccinated GroupsData comparing vaccinated and unvaccinated children show a consistent pattern of vaccinated children having multiple times the rate of various chronic health issues. Sampling:\n50Study LinkAuthor AffiliationsFindingshttps://pmc.ncbi.nlm.nih.gov/articles/PMC7268563/ Simpson University (CA) and Institute of Medical and Scientific Inquiry (NM)Vaccination before 1year of age was associated with increased odds of developmental delays (OR=2.18, 95% CI 1.47–3.24), asthma (OR=4.49, 95% CI 2.04–9.88) and ear infections (OR=2.13, 95% CI 1.63–2.78).https://doi.org/10.1080/02772240701806501State University of New York at Stony BrookThe odds of receiving early intervention or special education services were 8.63 times as great (OR=8.63, 95% CI 3.24–22.98) for vaccinated boys as for unvaccinated boys after adjustment for confounders.https://pubmed.ncbi.nlm.nih.gov/21058170/ State University of New York at Stony BrookMale neonates vaccinated with the hepatitis B vaccine had a 3 times risk (OR=3.002, 95% CI 1.109-8.126) for parental report of autism diagnosis compared to boys not vaccinated as neonates during that same time period.https://www.oatext.com/pdf/JTS-3-187.pdf Jackson State University (MS)Vaccination associated with neurodevelopmental disorders (NDD) in children born at term (OR 2.7, 95% CI: 1.2, 6.0). Vaccination and preterm birth had 5.4 times risk (95% CI: 2.5, 11.9) compared to vaccinated but non-preterm children, and 14.5 times risk (95% CI: 5.4, 38.7) compared to neither preterm nor vaccinated. https://www.oatext.com/pdf/JTS-3-186.pdf Jackson State University (MS)Vaccinated children compared to unvaccinated more likely to be been diagnosed with: allergic rhinitis (10.4% vs. 0.4%, p <0.001), other allergies (22.2% vs. 6.9%, p <0.001), eczema/ atopic dermatitis (9.5% vs. 3.6%, p = 0.035), a learning disability (5.7% vs. 1.2%, p = 0.003), ADHD (4.7% vs. 1.0%, p =0.013), ASD (4.7% vs. 1.0%, p = 0.013), any neurodevelopmental disorder (10.5% vs. 3.1%, p<0.001) and any chronic illness (44.0% vs. 25.0%, p <0.001). https://pubmed.ncbi.nlm.nih.gov/15805992/ Vanderbilt University (TN)In multiple regression analyses there were significant ( P < .0005) and dose-dependent negative relationships between vaccination refusal and self-reported asthma or hay fever only in children with no family history of the condition and, for asthma, in children with no exposure to antibiotics during infancy.\nPost-Licensure Safety of the U.S. Vaccine ScheduleExamples of Generally Unreliable Studies•Comparing vaccinated children with vaccinated children•Using risk windows post-vaccination\n51\nPost-Licensure Safety of the U.S. Vaccine ScheduleRise in Chronic DiseasesMost of the disease contributing to the increase are related to some form of immune system deregulation, including asthma, allergies, ADHD, etc., as discussed in the accompanying memorandum. Many are also disclosed in Section 6.2 of one or more vaccine package inserts.Source: https://pubmed.ncbi.nlm.nih.gov/3944229/ (https://perma.cc/NGA9-93KW) (“According to data from the National Health Interview Survey (NHIS) [1979-1981] over two million children under 17 years (3.8%) are afflicted by chronic conditions that cause some limitation of activity.”); https://pmc.ncbi.nlm.nih.gov/articles/PMC1646496/ (https://perma.cc/KN4A-94TV) (“Data from the National Health Interview Survey indicate that the prevalence of activity-limiting chronic conditions among children under age 17 years doubled between 1960 and 1981, from 1.8 to 3.8 per cent.”); https://pubmed.ncbi.nlm.nih.gov/9551003/ (https://perma.cc/JTZ5-JBNK) (Among “children younger than 18 years who were included in the 1992-1994 National Health Interview Survey … [a] significant proportion of children, estimated at 6.5% of all US children, experienced some degree of disability.”); https://www.cdc.gov/chronic-disease/about/index.html (https://perma.cc/N4GT-38L2) (“Chronic diseases are defined broadly as conditions that last 1 year or more and require ongoing medical attention or limit activities of daily living or both.”).52Year(s)Percent of Childrenwith a Chronic DiseaseEarly 1980sPresent<10%>40%Year(s)Percent of Children with a Chronic Disease\nPost-Licensure Safety of the U.S. Vaccine ScheduleAluminum Adjuvants\nSource: https://pubmed.ncbi.nlm.nih.gov/33887692/. See memorandum for additional sources.\nFinding: Six vaccines (Pentacel, Havrix, Adacel, Pedvax, Prevnar 13, Vaqta) contained a statistically significant greater quantity and four vaccines (Infanrix, Kinrix, Pediarix, and Synflorix) contained a statistically significant lower quantity of aluminum adjuvant than listed on the product’s label.53\nPost-Licensure Safety of the U.S. Vaccine SchedulePost-Licensure Safety•When robust clinical trial data is not possible to obtain, robust post-licensure safety data should support recommendations.•Condition recommendations on sponsors providing any requested follow-up safety data.•Revisit recommendations regularly.\n54\nEfficacy in Preventing Transmission: U.S. Childhood Vaccine Schedule\nEfficacy of the U.S. Vaccine ScheduleTransmission\n56Some live-attenuated vaccines, such as Varivax for varicella, generally prevent transmission of the target pathogen in most recipients for an extended duration post-vaccination.  \nSource: see accompanying memorandum. Live-Attenuated Vaccines\nEfficacy of the U.S. Vaccine ScheduleTransmission\n57“IPV does not prevent intestinal infection and therefore does not prevent poliovirus transmission”Source: https://www.cdc.gov/mmwr/volumes/71/wr/mm7133e2.htm Polio\n\nEfficacy of the U.S. Vaccine ScheduleTransmission\n58Source: https://www.cdc.gov/orr/polioviruscontainment/diseaseandvirus.htmPolio\n\nEfficacy of the U.S. Vaccine ScheduleTransmission\n59Source: https://pubmed.ncbi.nlm.nih.gov/24277828/ Pertussis\n\nEfficacy of the U.S. Vaccine ScheduleTransmission\n60Source: https://pubmed.ncbi.nlm.nih.gov/31333640/ Pertussis“Natural infection [with pertussis] evokes both mucosal and systemic immune responses, while aPVs [acellular pertussis vaccines] include only a systemic immune response. … Mucosal immunity is essential to prevent colonization and transmission of B. pertussis organism. Consequently, preventive measures such as aPVs that do not induce a valid mucosal response can prevent disease but cannot avoid infection and transmission. … aPV pertussis vaccines do not prevent colonization. Consequently, they do not reduce the circulation of B. pertussis and do not exert any herd immunity effect.”\n\nEfficacy of the U.S. Vaccine ScheduleTransmission\n61Source: https://pubmed.ncbi.nlm.nih.gov/29180031/Pertussis\n“That vaccination does not prevent B. pertussis infection in humans, nor the circulation of the organism in human populations in any important manner, comes from the observation that the inter-epidemic intervals have not changed in a major way since the implementation of mass vaccination.” \n\nEfficacy of the U.S. Vaccine ScheduleTransmission\n62Source: https://pubmed.ncbi.nlm.nih.gov/31333640/ Pertussis“FDA’s licensure standards for vaccines do not require demonstration of the prevention of infection or transmission. … [T]he pertussis vaccines that FDA has licensed are for prevention of pertussis disease not infection with B. pertussis.” FDA is also not “convinced that there is a any widespread misconception about this.”\n\nEfficacy of the U.S. Vaccine ScheduleTransmission\n63Source: https://www.cdc.gov/acip/vaccine-recommendations/shared-clinical-decision-making.html“Unlike routine, catch-up, and risk-based recommendations … ACIP makes shared clinical decision-making recommendations when individuals may benefit from vaccination, but broad vaccination of people in that group is unlikely to have population-level impacts.”\n\nEfficacy in Preventing Mortality:U.S. Childhood Vaccine Schedule\nEfficacy of the U.S. Vaccine ScheduleBenefits\n65Vaccines are intended to prevent symptoms if the vaccinee is infected with the target pathogen, thereby potentially preventing disease and mortality.\nEfficacy of the U.S. Vaccine ScheduleClaimed Benefits\n66Source: https://www.cdc.gov/mmwr/volumes/73/wr/mm7331a2.htm“Among children born during 1994–2023, routine childhood vaccinations will have prevented approximately 508 million cases of illness, 32 million hospitalizations, and 1,129,000 deaths”\n\nEfficacy of the U.S. Vaccine ScheduleClaimed Benefits: Mortality\n67Source: https://www.cdc.gov/mmwr/preview/mmwrhtml/su6004a2.htm-Ignores all confounders, explaining “factors other than immunization (e.g., hygiene…) might have contributed to lower disease risks in recent decades, and reductions resulting from these contributions have not been incorporated into the model”-No confidence intervals-Data is unreliable-Clearance process versus peer-review\n\nEfficacy of the U.S. Vaccine ScheduleClaimed Benefits: Mortality\n68\nU.S. Public Health Service Report\n2023 MMWR Report: Claims 25,000 diphtheria deaths prevented each year between 1994 and 2023, totaling 750,000 of the 1.1 million lives.CDC Mortality Data: 634 diphtheria deaths in 1948\nSource: https://stacks.cdc.gov/view/cdc/6200; https://www.cdc.gov/nchs/data/vsus/VSUS_1948_2.pdf   \nEfficacy of the U.S. Vaccine ScheduleClaimed Benefits: Mortality\n69Source: https://web.archive.org/web/20190615081539/https://www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendices/e/reported-cases.pdf MMWR Report: Claims 3,003 Hepatitis B deaths prevented each year between 1994 and 2023 (totaling 90,100 of the 1.1 million lives).CDC Pink Book: There were 294 deaths from Hepatitis B in 1980, the year before the first Hep B vaccine was introduced in 1981. \nEfficacy of the U.S. Vaccine ScheduleClaimed Benefits: Mortality\n70Source: https://stacks.cdc.gov/view/cdc/6200; https://web.archive.org/web/20190615081539/https://www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendices/e/reported-cases.pdf  \n2023 MMWR Report: claims 2,833 measles deaths prevented each year between 1994 and 2023 (totaling 85,000 of the 1.1 million lives)CDC Mortality Data: 407 measles deaths in 1962 after an over 98% decline in mortality between 1900 and 1962U.S. Public Health Service Report\nEfficacy of the U.S. Vaccine ScheduleClaimed Benefit: Mortality\n71Studies on non-specific effects on mortality in children: live v. non-live vaccines and developed v. developing countries\nEfficacy of the U.S. Vaccine ScheduleClaimed Benefit: Mortality\n72Source: https://pubmed.ncbi.nlm.nih.gov/26122188/   \n!!\n!!\n\nEfficacy of the U.S. Vaccine Schedule\n73Pneumococcal deaths are during childhood. Mortality data for: diphtheria, pertussis, and tetanus (https://www.cdc.gov/nchs/data/vsus/VSUS_1948_2.pdf, p.440, https://perma.cc/N2PN-5UPU);polio, measles, mumps, rubella, hepatitis B, hepatitis A, and varicella (https://web.archive.org/web/20190615081539/https:// www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendices/e/reported-cases.pdf,https://per-ma.cc/7GPK-32AC); Hib (There was an ineffective vaccine introduced in 1985 and withdrawn. After a Hib vaccine considered effective for infants was first licensedinlate 1990, the CDC in 1991 for the first time recommended a Hib vaccine for infants, and by 1992 vaccine uptake was only 28%. There were 17 deaths in 1991 from Hib, so to be conservative, this death number was doubled to 34 for the chart. See discussion regarding Hib vaccine in this chapter for sup-porting citations.); pneumococcal (“Before routine use of pneumococcal conjugate vaccine in 2000, the burden of pneumococcal disease among children younger than age 5 years was … 200 deaths from invasive pneumococcal disease.” Hence, this CDC estimate was used even though it appears inflated based on other data. https://www.cdc.gov/pinkbook/hcp/table-of-contents/chapter-17-pneumococcal-disease.html, https://perma.cc/6YQT-F4CA);and rotavirus and meningococcal (CDC listing, “Deaths per year in the United States prior to recommended vaccines,” for these diseases on slide 7: https://web.archive.org/web/20240518044830/https:// www.cdc.gov/vaccines/acip/meetings/downloads/slides-2022-05-19/01- COVID-Daley-508.pdf, https://perma.cc/VV9F-C77B).Claimed Benefit: MortalityDisease Year VaccineLicensedDiphtheria 634 Pertussis 1949 (DTP) 1,146 Tetanus 506 Polio 1955 1,368 Measles 1963 408 Mumps 1967 43 Rubella 1969 24 Hepatitis B 1981 294 Hib 1990 34 Hepatitis A 1995 97 Varicella 1995 124 Pneumococcal 2000 200 Meningococcal 2005 8 Rotavirus 2006 20 Number of Deaths in YearPrior to Licensure\nInformed Consent & Considerations\nInformed ConsentInformed Consent“Unlike routine, catch-up, and risk-based recommendations, … shared clinical decision-making recommendations are individually based and informed by a decision process between the health care provider and the patient or parent/guardian.”\n75Source: https://www.cdc.gov/acip/vaccine-recommendations/shared-clinical-decision-making.html\n\nInformed ConsentItems to Consider-Revisit prior recommendations made without robust data. -Require robust trial and, when possible, post-licensure safety data.-Liaison members should respect right of informed consent. \n76", "summary": "Development of the U.S. Childhood Vaccine Schedule Aaron SiriACIP Meeting, December 5, 2025With A Focus on Suggested Improvements DisclosuresManaging Partner of Siri & Glimstad LLP with 100+ professionals who handle civil rights, exemptions, immigration, employment, and injury claims related to vaccination. Author of Vaccines, Amen: The Religion of Vaccines. 2  Growth of U.S. Childhood Vaccine Schedule Growth of U.S. Vaccine Schedule…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-december-04-05-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-12-04-05/01-siri-child-imz-schedule-508.pdf", "doc_date": "2025-12-04", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 76}
{"title": "04 Dengue Kaul 508", "content": "Summary of two economic\nmodels for dengue vaccine\nTAK-003 use in Puerto Rico\nAdvisory Committee on Immunization Practices \n \nJune 22, 2023 \nThe models summarized are currently undergoing the CDC economic review following the ACIP \nGuidance for Health Economics Studies, so results should be considered as preliminary.RajReni Kaul, PhD\nCDC/NCIRD/ISD\nThe findings and conclusions in this presentation are those of the author(s) and do not \nnecessarily represent the views of the Centers for Disease Control and Prevention.\nAcknowledgements\n•This presentation summarizes work conducted by two modeling \nteams\n•Notre Dame team contracted by CDC (ND/CDC Model)\n•Guido España , Manar Alkuzweny , Alex Perkins\n•Takeda team (Takeda Model)\n•J. Shen, R. Hanley, I. Zerda , et al. \n•CDC and ACIP contributors and reviewers\n•Dengue ACIP workgroup\n•Economists at CDC and colleagues (NCIRD/ISD)\nConflicts of Interest Statements\n•RajReni Kaul: None.\n•Notre Dame team:\n•Dr. Guido España and Dr. Alex Perkins have previously received research \nfunding from GlaxoSmithKline to support unrelated research on dengue \nvaccine development.\n•Dr. Alex Perkins currently receives research funding and consulting fees\nfrom Emergent Biosciences to support unrelated research on\nchikungunya vaccine development.\n•Takeda team:\n•Takeda is the developer and manufacturer of the TAK -003 vaccine.\n•Directly employed by Takeda or consultants employed by Putnam PHMR and \ncontracted by Takeda\nTerminology\nAbbreviation Full term/Meaning\nND/CDC Notre Dame/CDC model\nVE Vaccine efficacy\nDENV (e.g., DENV -3) Dengue virus (e.g., serotype 3 dengue virus)\nPICO Policy question articulated as Population, Intervention, Comparison, Outcomes\nCase Medically -attended case\nHosp Hospitalization\nAdditional hospitalizations Hospitalization induced by vaccine -enhanced disease\nNNV Number needed to vaccinate to avert an outcome (e.g., NNV hospitalization)\nQALY Quality -adjusted life -years\nAll values rounded to 3 significant figures. \nOutline\n•Recap of PICO questions\n•Overview of models\n•Comparison of results\n•Exploring differences in assumptions\n•QALY values used, vaccine efficacy\n•Summary of Takeda model results \n•Base case\n•Scenario analysis\n•Model comparison summary and limitations\n•Application to PICO questions\nPICO Questions\n•Should two doses of TAK -003 be administered routinely to seropositive\npersons aged 4 –16 years living in dengue -endemic areas?\n•Should two doses of TAK -003 be administered routinely to seronegative\npersons aged 4 –16 years living in dengue -endemic areas?\n•Should two doses of TAK -003 be administered routinely to seropositive\npersons aged 17 –60years living in dengue -endemic areas?\n•Should two doses of TAK -003 be administered routinely to seronegative\npersons aged 17 –60years living in dengue -endemic areas?\nGeneral Model Design\nAssumption/Model Characteristic Notre Dame/CDC Takeda\nModel type Stochastic individual -based model Deterministic compartmental model\nPrevaccination screening Included Not included\nVaccine implementation Age range, varying coverage rate over \ntimeSingle age, a catch -up routine in year \n1possible, varying coverage rate over \nfirst four years then constant \nthereafter\nSerotype specific VE point \nestimatePoint estimate estimated using multi -\nlevel Bayesian modelPoint estimate estimated using \ntraditional methods from clinical trial*\nSerotype specific VE ranges Each simulation used VE inputs \nsampled from the confidence interval \naround the point estimateNo range, only point estimate used\nGeographic area San Juan municipality (N=280,000) Puerto Rico (N= 3,256,028 )\nDENV caused deaths Not included in QALYs Included in QALYs\nAssumption/Model Characteristic Notre Dame/CDC Takeda\nModel type Stochastic individual -based model Deterministic compartmental model\nPrevaccination screening Included Not included\nVaccine implementation Age range, varying coverage rate over \ntimeSingle age, a catch -up routine in year \n1possible, varying coverage rate over \nfirst four years then constant thereafter\nSerotype specific VE point \nestimatePoint estimate estimated using multi -\nlevel Bayesian modelPoint estimate estimated using \ntraditional methods from clinical trial*\nSerotype specific VE ranges Each simulation used VE inputs \nsampled from the confidence interval \naround the point estimateNo range, only point estimate used\n* When the clinical trial estimate was negative or confidence interval included negative values, a VE model input of zero was assumed.Geographic area San Juan municipality (N=280,000) Puerto Rico (N= 3,256,028 )\nDENV caused deaths Not included in QALYs Included in QALYsGeneral Model Design\nAssumption/Model Characteristic Notre Dame/CDC Takeda\nModel type Stochastic individual -based model Deterministic compartmental model\nPrevaccination screening Included Not included\nVaccine implementation Age range, varying coverage rate over \ntimeSingle age, a catch -up routine in year \n1possible, varying coverage rate over \nfirst four years then constant thereafter\nSerotype specific VE point \nestimatePoint estimate estimated using multi -\nlevel Bayesian modelPoint estimate estimated using \ntraditional methods from clinical trial*\nSerotype specific VE ranges Each simulation used VE inputs \nsampled from the confidence interval \naround the point estimateNo range, only point estimate used\nGeographic area San Juan municipality (N=280,000) Puerto Rico (N= 3,256,028 )General Model Design\n* When the clinical trial estimate was negative or confidence interval included negative values, a VE model input of zero was assumed.DENV caused deaths Not included in QALYs Included in QALYs\nGeneral Model Design\nAssumption/Model Characteristic Notre Dame/CDC Takeda\nModel type Stochastic individual -based model Deterministic compartmental model\nPrevaccination screening Included Not included\nVaccine implementation Age range, varying coverage rate over \ntimeSingle age, a catch -up routine in year \n1possible, varying coverage rate over \nfirst four years then constant thereafter\nSerotype specific VE point \nestimatePoint estimate estimated using multi -\nlevel Bayesian modelPoint estimate estimated using \ntraditional methods from clinical trial*\nSerotype specific VE ranges Each simulation used VE inputs \nsampled from the confidence interval \naround the point estimateNo range, only point estimate used\nGeographic area San Juan municipality (N=280,000) Puerto Rico (N= 3,256,028 )\nDENV caused deaths Not included in QALYs Included in QALYs\n* When the clinical trial estimate was negative or confidence interval included negative values, a VE model input of zero was assumed.\nEconomic Model Preliminary Results by PICO\nAge 4-16 years\nModelScenario conditionsNumber \nvaccinatedNet number averted with vaccination §\n$/QALY \n(ICER)§ Geographic \nArea† AgePrevaccination \nscreening Cases Hospitalizations Deaths\nND/CDCSan Juan \nMunicipality4-16 Yes 11,700 485 (1.2%) 182 (2.6%) 1 (2.9%) 182,000 *\nND/CDCSan Juan \nMunicipality4-16 No 30,300 1,070 (2.5%) 192 (2.8%) 1 (2.9%) 255,000 *\nTakeda Puerto Rico8, \ncatch -\nup 9 -16 No 157,000 46,700 (12%) 9,150 (14 %) 5 (13%) Cost -\nsaving\n†Modeled population size is 280,000 for the San Juan Municipality (ND/CDC model) and 3,256,028 for all of Puerto Rico (Takeda model).\n§When compared to no vaccination\n*Death is not incorporated into QALYs gained in the ND/CDC model base case assumptions. If QALY gains from averted deaths wer e \nincluded, then the ICERs would change from $182,000 to $65,000 per QALY for the scenario with prevaccination screening and would \nchange from $255,000 to $137,000 per QALY for the scenario without prevaccination screening.\nEconomic Model Preliminary Results by PICO\nAge 4-16 years\nModelScenario conditionsNumber \nvaccinatedNet number averted with vaccination §\n$/QALY \n(ICER)§ Geographic \nArea† AgePrevaccination \nscreening Cases Hospitalizations Deaths\nND/CDCSan Juan \nMunicipality4-16 Yes 11,700 485 (1.2%) 182 (2.6%) 1 (2.9%) 182,000 *\nND/CDCSan Juan \nMunicipality4-16 No 30,300 1,070 (2.5%) 192 (2.8%) 1 (2.9%) 255,000 *\nTakeda Puerto Rico8, \ncatch -\nup 9 -16 No 157,000 46,700 (12%) 9,150 (14 %) 5 (13%) Cost -\nsaving\n†Modeled population size is 280,000 for the San Juan Municipality (ND/CDC model) and 3,256,028 for all of Puerto Rico (Takeda model).\n§When compared to no vaccination\n*Death is not incorporated into QALYs gained in the ND/CDC model base case assumptions. If QALY gains from averted deaths wer e \nincluded, then the ICERs would change from $182,000 to $65,000 per QALY for the scenario with prevaccination screening, and would \nchange from $255,000 to $137,000 per QALY for the scenario without prevaccination screening.\nModelScenario conditionsNumber \nvaccinatedNet number averted with vaccination§\n$/QALY \n(ICER)§ Geographic \nArea† AgePrevaccination \nscreening Cases Hospitalizations Deaths\nND/CDCSan Juan \nMunicipality17-60 Yes 105,000 2,710 (6%) 724 (10%) 5(11%) 397,000 *\nND/CDCSan Juan \nMunicipality17-60 No 121,000 3,360 (8%) 928 (13%) 4(14%) 315,000 *\nTakeda Puerto Rico17, \ncatch -\nup 18 -\n60No 449,000 67,000 (17%) 13,100 (21%) 8 (21%)Cost -\nsaving\n†Modeled population size is 280,000 for the San Juan Municipality (ND/CDC model) and 3,256,028 for all of Puerto Rico (Takeda model).\n§When compared to no vaccination\n*Death is not incorporated into QALYs gained in the ND/CDC model base case assumptions. If QALY gains from averted deaths \nwere included, then the ICERs would change from $397,000 to $188,000 per QALY for the scenario with prevaccination screening, \nand would change from $315,000 to $153,000 per QALY for the scenario without prevaccination screening.Economic Model Preliminary Results by PICO\nAge 17-60 years\nModelScenario conditionsNumber \nvaccinatedNet number averted with vaccination§\n$/QALY \n(ICER)§ Geographic \nArea† AgePrevaccination \nscreening Cases Hospitalizations Deaths\nND/CDCSan Juan \nMunicipality17-60 Yes 105,000 2,710 (6%) 724 (10%) 5(11%) 397,000 *\nND/CDCSan Juan \nMunicipality17-60 No 121,000 3,360 (8%) 928 (13%) 4(14%) 315,000 *\nTakeda Puerto Rico17, \ncatch -\nup 18 -\n60No 449,000 67,000 (17%) 13,100 (21%) 8 (21%)Cost -\nsaving\n†Modeled population size is 280,000 for the San Juan Municipality (ND/CDC model) and 3,256,028 for all of Puerto Rico (Takeda model).\n§When compared to no vaccination\n*Death is not incorporated into QALYs gained in the ND/CDC model base case assumptions. If QALY gains from averted deaths \nwere included, then the ICERs would change from $397,000 to $188,000 per QALY for the scenario with prevaccination screening, \nand would change from $315,000 to $153,000 per QALY for the scenario without prevaccination screening.Economic Model Preliminary Results by PICO\nAge 17-60 years\nExploring Difference\nModel Inputs : QALY loss from dengue episodes\nDisease OutcomeQuality -adjusted \ndays lost\nND/CDC Takeda\nNon -hospitalized dengue 11.2§5.5\nHospitalized dengue 12.8§6.8\nPersistent dengue after non -hospitalized or \nhospitalized caseNA 4.9*\nDengue caused deaths NAAge-\ndependent\n§QALY lost for dengue episodes includes persistent dengue in 34% of all cases.\n* Model assumes 34% of dengue episodes aged 30 or older develop persistent symptoms.\nDisease OutcomeQuality -adjusted \ndays lost\nND/CDC Takeda\nNon -hospitalized dengue 11.2§6.1†\nHospitalized dengue 12.8§7.2†\nPersistent dengue after non -hospitalized or \nhospitalized caseNA -\nDengue caused deaths NAAge-\ndependentExploring Difference\nModel Inputs : QALY loss from dengue episodes\nWhen persistent \ndengue QALY loss is \ncombined with \nacute phase QALY \nloss\n§QALY lost for dengue episodes includes persistent dengue in 34% of all cases.\n† Calculated as if 34% of cases ages 30 or older develop persistent symptoms. \nExploring Difference\nModel Inputs : Vaccine Efficacy \n68.1%\n(27.2, 86.2)\nTakeda 75.8% 98.5% 0%# 0%§ 75.8% 98.5% 71.4% 100%-4\nNon -\nhospitalized \nSymptomatic \ncaseND/CDC*29.7% \n(6.7, 48.5)96.3% \n(87.1, 100)30.0%\n(7.8, 49.4)-1.1%\n(-73.5,64.4)63.1% \n(52.7, 82.2)85.2% \n(75.6, 94.4)42.5% \n(26.4, 55.8)60.2%Vaccine efficacy inputs by serostatus and by dengue serotype\nSeronegative at vaccination Seropositive at vaccination\nDENV -1 DENV -2 DENV -3 DENV -4 DENV -1 DENV -2 DENV -3 DENV\n(19.8, 89.6)\nTakeda† 30.8 % 69.8 % 0%#0%#46.7 % 69.8 % 42.6 % 61.2 %\nHospitalized \ncaseND/CDC*84.6% \n(54.5, 98.7)99.0% Model\n(95.6, 100)-30.3% \n(-91.6, 25.6)39.2% \n(-20.4, 81.0)54.1% \n(13.3, 82.2)99.5% \n(97.8, 100)70.2% \n(45.6, 90.4)Disease \nOutcome\n29.7% \n(6.7, 48.5)96.3% \n(87.1, 100)30.0%\n(7.8, 49.4)-1.1%\n(-73.5,64.4)63.1% \n(52.7, 82.2)85.2% \n(75.6, 94.4)42.5% \n(26.4, 55.8)60.2%\n(19.8, 89.6)\nTakeda† 30.8 % 69.8 % 0%#0%#46.7 % 69.8 % 42.6 % 61.2 %\nHospitalized \ncaseND/CDC*84.6% \n(54.5, 98.7)99.0% \n(95.6, 100)-30.3% \n(-91.6, 25.6)39.2% \n(-20.4, 81.0)54.1% \n(13.3, 82.2)99.5% \n(97.8, 100)70.2% \n(45.6, 90.4)68.1%\n(27.2, 86.2)\nTakeda 75.8% 98.5% 0%# 0%§ 75.8% 98.5% 71.4% 100%Exploring Difference\nModel Inputs : Vaccine Efficacy\n* Point estimate with 95% confidence interval\n† Non -hospitalized case\n§Due to lack of data* Point estimate with 95% confidence interval\n† Average VE over 5 years post -vaccination. Includes vaccine waning.\n§Due to lack of data\n#Value used because pivotal clinical trial estimate or confidence interval included negative valuesDisease \nOutcomeModelVaccine efficacy inputs by serostatus and by dengue serotype\nSeronegative at vaccination Seropositive at vaccination\nDENV -1 DENV -2 DENV -3 DENV -4 DENV -1 DENV -2 DENV -3 DENV -4\nNon -\nhospitalized \nSymptomatic \ncaseND/CDC*\nDisease \nOutcomeModelVaccine efficacy inputs by serostatus and by dengue serotype\nSeronegative at vaccination Seropositive at vaccination\nDENV -1 DENV -2 DENV -3 DENV -4 DENV -1 DENV -2 DENV -3 DENV -4\nNon -\nhospitalized \nSymptomatic \ncaseND/CDC*29.7% \n(6.7, 48.5)96.3% \n(87.1, 100)30.0%\n(7.8, 49.4)-1.1%\n(-73.5,64.4)63.1% \n(52.7, 82.2)85.2% \n(75.6, 94.4)42.5% \n(26.4, 55.8)60.2%\n(19.8, 89.6)\nTakeda† 30.8 % 69.8 % 0%#0%#46.7 % 69.8 % 42.6 % 61.2 %\nHospitalized \ncaseND/CDC*84.6% \n(54.5, 98.7)99.0% \n(95.6, 100)-30.3% \n(-91.6, 25.6)39.2% \n(-20.4, 81.0)54.1% \n(13.3, 82.2)99.5% \n(97.8, 100)70.2% \n(45.6, 90.4)68.1%\n(27.2, 86.2)\nTakeda 75.8% 98.5% 0%# 0%§ 75.8% 98.5% 71.4% 100%\n* Point estimate with 95% confidence interval\n† Average VE over 5 years post -vaccination. Includes vaccine waning. \n§Due to lack of data\n#Value used because pivotal clinical trial estimate or confidence interval included negative valuesExploring Difference\nModel Inputs : Vaccine Efficacy\nDisease \nOutcomeModelVaccine efficacy inputs by serostatus and by dengue serotype\nSeronegative at vaccination Seropositive at vaccination\nDENV -1 DENV -2 DENV -3 DENV -4 DENV -1 DENV -2 DENV -3 DENV -4\nNon -\nhospitalized \nsymptomatic \ncaseND/CDC*29.7% \n(6.7, 48.5)96.3% \n(87.1, 100)30.0%\n(7.8, 49.4)-1.1%\n(-73.5,64.4)63.1% \n(52.7, 82.2)85.2% \n(75.6, 94.4)42.5% \n(26.4, 55.8)60.2%\n(19.8, 89.6)\nTakeda† 30.8 % 69.8 % 0%#0%#46.7 % 69.8 % 42.6 % 61.2 %\nHospitalized \ncaseND/CDC*84.6% \n(54.5, 98.7)99.0% \n(95.6, 100)-30.3% \n(-91.6, 25.6)39.2% \n(-20.4, 81.0)54.1% \n(13.3, 82.2)99.5% \n(97.8, 100)70.2% \n(45.6, 90.4)68.1%\n(27.2, 86.2)\nTakeda 75.8% 98.5% 0%# 0%§ 75.8% 98.5% 71.4% 100%Exploring Difference\nModel Inputs : Vaccine Efficacy \n* Point estimate with 95% confidence interval\n† Average VE over 5 years post -vaccination. Includes vaccine waning. \n§Due to lack of data\n#Value used because pivotal clinical trial estimate or confidence interval included negative values\nDisease \nOutcomeModelVaccine efficacy inputs by serostatus and by dengue serotype\nSeronegative at vaccination Seropositive at vaccination\nDENV -1 DENV -2 DENV -3 DENV -4 DENV -1 DENV -2 DENV -3 DENV -4\nNon -\nhospitalized \nsymptomatic \ncaseND/CDC*29.7% \n(6.7, 48.5)96.3% \n(87.1, 100)30.0%\n(7.8, 49.4)-1.1%\n(-73.5,64.4)63.1% \n(52.7, 82.2)85.2% \n(75.6, 94.4)42.5% \n(26.4, 55.8)60.2%\n(19.8, 89.6)\nTakeda† 30.8 % 69.8 % 0%#0%#46.7 % 69.8 % 42.6 % 61.2 %\nHospitalized \ncaseND/CDC*84.6% \n(54.5, 98.7)99.0% \n(95.6, 100)-30.3% \n(-91.6, 25.6)39.2% \n(-20.4, 81.0)54.1% \n(13.3, 82.2)99.5% \n(97.8, 100)70.2% \n(45.6, 90.4)68.1%\n(27.2, 86.2)\nTakeda 75.8% 98.5% 0%# 0%§ 75.8% 98.5% 71.4% 100%Exploring Difference\nModel Inputs : Vaccine Efficacy \n* Point estimate with 95% confidence interval\n† Average VE over 5 years post -vaccination. Includes vaccine waning. \n§Due to lack of data\n#Value used because pivotal clinical trial estimate or confidence interval included negative values\nExploring Difference\nImpact of vaccine efficacy inputs on outcome\n•What if the ND/CDC model uses the Takeda VE inputs in the scenario \nwhere 4 –16-year -olds are vaccinated without screening?\n•Takeda’s VE inputs did not substantially impact the results of the ND/CDC \nmodel. \nVE \ninputsNumber \nvaccinatedNet number averted with vaccination Vaccination enhanced \ndisease NNV \nhosp.QALYs \ngained*$/QALY \n(ICER)*\nCases Hosp. DeathsAdditional \ncasesAdditional \nhosp.\nND/CDC† 30,300 1,070\n(651 -1,470) 192 \n(112 -300)1 \n(0.5 -1.5)45\n(35-52)32 \n(29-37)158 \n(101 -270)35 255,000 \nTakeda† 30,300 1,030 \n(699 -1,300) 287 \n(197 -425)1\n(0.9 -2.1)NA NA 105 \n(71-153)34 262,000 \n*QALY loss due to dengue caused death is not incorporated into ICER calculation.\n†Range of model results due to stochasticity\nOutline\n•Recap of PICO questions\n•Overview of models\n•Comparison of results\n•Exploring differences in assumptions\n•QALY values used, vaccine efficacy\n•Summary of Takeda model results \n•Base case\n•Scenario analysis\n•Model comparison summary and limitations\n•Application to PICO questions\nTakeda Base Case Preliminary Results\nRoutine vaccination at age 8\nBase case conditions\n•Entire population of Puerto Rico\n•20-year time horizon\n•Routine vaccination at age 8\n•Vaccination rate increases from \n0% at year 0 to 60% at year 4.\n•Using slightly different QALY loss \nthan previously presented*Base Case\nNumber vaccinated 449,000\nAverted cases 123,000 (15%)\nAverted hospitalizations 25,000 (20%)\nAverted deaths 15 (20%)\nNNV hospitalization 17.6\nQALY sgained 2,070\n$/QALY Cost -saving\n$/hospitalization Cost -saving\n*Values reported in supplemental slides\nScenario Analysis\nTakeda Model: Routine vaccination at age 8\n*Used a fixed vaccine coverage parameter of 21.5% to approximate vaccination \ncoverage that increases from 0% to 43% over 10 years.Scenario\nNumber \nvaccinatedNumber averted with vaccination\nNNV \nhospQALYs \ngainedICER \n($/QALY)Time \n(years)TAK-003 \nroutine \nageTAK-003 \ncatchup \nageTAK-003 \ncoverage*Cases Hosp Deaths\n10 8 None 22% 87,000 24,000 (6%) 4,510 (7%) 3 (8%) 19.3 402Cost -\nsaving\n10 8 9-16 22% 157,000 47,000 (12%) 9,150 (14%) 5 (13%) 17.1 838Cost -\nsaving\nOverall Cost -effectiveness\nPreliminary results\nIncremental Cost (in thousands)\nQALYs gained\nOverall Cost-effectiveness\nPreliminary results\n                               \n                \n      \n      \nIncremental Cost (in thousands)\nQALYs gained\n4-16 \nw/prevaccination\nscreening17-60 w/o \nprevaccination\nscreeningR8 \nCatch-up 9- 16R17 \nCatch-up 18- 60\nLimitations\n•Parameter Uncertainty\n•Large confidence interval (>100%) for DENV -3 and DENV -4 VE estimates for \nthose seronegative at vaccination.\n•Given vaccine’s range in serotype specific efficacy, actual outcome will \nbe heavily influenced by the dominant circulating serotype.\n•In the ND/CDC model, deaths were not part of the QALY calculation.\n•Using Takeda’s model, we cannot assess benefits and risks of pre -\nvaccination screening strategies vs strategies without pre -vaccination \nscreening.The models summarized are currently undergoing the CDC economic review following the ACIP \nGuidance for Health Economics Studies, so results should be considered as preliminary.\nOnly seropositives \n(prescreening)All individuals \n(no prescreening)\n4–16 years\nChildren/AdolescentsAnswered by ND/CDC ModelAnswered by ND/CDC Model\n& Takeda Model\n17–60 years\nAdultsAnswered by ND/CDC ModelAnswered by ND/CDC Model\n& Takeda ModelModels answering the PICO Questions\nAcknowledgements\n•This presentation summarized work conducted by two modeling \nteams\n•Notre Dame team contracted by CDC (ND/CDC Model)\n•Guido España , Manar Alkuzweny , Alex Perkins\n•Takeda team (Takeda Model)\n•J. Shen, R. Hanley, I. Zerda *, Z.  Janusz *, E. Kharitonova*, A. Rosas, A. Garcia, M. Curtis, \nM. Lu, C. Ruff, V. Tricou , M. Sharma, R. Kastner, E. Lloyd, G. Perez, S. Biswal, T. Tsai, I. \nWillits*\n•Name with (*) are employed by Putnam PHMR and contracted by Takeda. All others are \ndirectly employed by Takeda. \n•CDC and ACIP contributors and reviewers\n•Dengue ACIP workgroup\n•Economists at CDC and colleagues (NCIRD/ISD)\nThe findings and conclusions in this presentation are those of the author(s) and do not \nnecessarily represent the views of the Centers for Disease Control and Prevention.", "summary": "Summary of two economic models for dengue vaccine TAK-003 use in Puerto Rico Advisory Committee on Immunization Practices    June 22, 2023  The models summarized are currently undergoing the CDC economic review following the ACIP  Guidance for Health Economics Studies, so results should be considered as preliminary.RajReni Kaul, PhD CDC/NCIRD/ISD The findings and conclusions in this presentation are those of the author(s) and do not  necessarily represent the views of the Centers for Disease…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/04-Dengue-Kaul-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 30}
{"title": "05 Dengue Wong 508", "content": "Centers for Disease Control and Prevention\nNational Center for Emerging and Zoonotic Infectious Diseases\nPartial Evidence to Recommendations \nFramework for Dengue Vaccine TAK -003\nJoshua Wong, MD\nACIP June 22, 2023\nDengue Branch, CDC\n\nGoals for Partial EtRPresentation\n•Summarize the extent of the Work Group deliberations to date\n•Present three Evidence to Recommendations ( EtR) domains*\n•Prepare ACIP for the next meeting which will include a full EtRpresentation, \nproposed recommendation, and vote.†During the full EtRpresentation:\n•Domains presented today will be summarized.\n•Work Group opinions and relevant summaries of straw polls will be presented.\n*Data from ND/CDC Modeling are preliminary and subject to change\n†Subject to change\nEvidence to Recommendations ( EtR) Framework\nEtR Domain Question\nPublic Health Problem •Is the problem (dengue) of public health importance?\nBenefits and Harms•What is the overall certainty of this evidence for the critical outcomes? \n•How substantial are the desirable anticipated effects of the intervention ( TAK-003\ndengue vaccine )?\n•How substantial are the undesirable anticipated effects?\n•Do the desirable effects outweigh the undesirable effects?\nValues•Does the target population feel the desirable effects are large relative to the  \nundesirable effects?\n•Is there important variability in how patients value theoutcomes?\nAcceptability •Is the intervention acceptable to keystakeholders?\nFeasibility •Is the intervention feasible to implement?\nResource Use •Is the intervention a reasonable and efficient allocation ofresources?\nEquity •What would be the impact of the intervention on health equity?\nPublic Health Problem\nIs the problem (dengue) of public health \nimportance?\nIs dengue a problem of public health \nimportance in dengue -endemic areas?\n1.Should two doses of TAK -003 be administered routinely to seropositive* \npersons aged 4 –16 years living in dengue -endemic areas?\n2.Should two doses of TAK -003 be administered routinely to seronegative \npersons aged 4 –16 years living in dengue -endemic areas?\n3.Should two doses of TAK -003 be administered routinely to seropositive* \npersons aged 17 –60 years living in dengue -endemic areas?\n4.Should two doses of TAK -003 be administered routinely to seronegative \npersons aged 17 –60 years living in dengue -endemic areas?\n*Recommendations for seropositive individuals only will require prevaccination screening for previous dengue virus infection.\nDengue is endemic in six U.S. territories and \nfreely associated states .\n\nPuerto Rico has the largest population \namong territories with endemic dengue.\n2020 data -census.gov Territory Population         (%)\nPuerto Rico 3,285,874  (96.0%)\nUS Virgin Islands 87,146    (2.5%)\nAmerican Samoa 49,710    (1.5%)\nTotal population at risk 3,422,730   (100%)\n020004000600080001000012000\n1 2 3 4 5 6 7 8 9 10 11Number of cases\nSeries1 Series2 Series3\n024681012\n1 2 3 4 5 6 7 8 9 10 11Incidence per 1,000 population\nSeries1 Series2 Series3Dengue cases and rates per 1,000 population\nin Puerto Rico , American Samoa , and USVI , 2010 –2020 \nRyff KR, Rivera A, Rodriguez DM, Santiago GA, Medina FA, Ellis EM, Torres J, Pobutsky A, Munoz -Jordan J, Paz -Bailey G, Adams \nLE. Epidemiologic Trends of Dengue in U.S. Territories, 2010 -2020. MMWR Surveill Summ . 2023 May 19;72(4):1 -12.\nSeropositive Seronegative\n4–16 years\nChildren/Adolescents\n17–60 years\nAdultsIs dengue a problem of public health importance \nfor children/adolescents living in endemic areas?\n*Immunogenicity in seropositive adults is expected to be at least as high as in seronegative adults.\nDengue cases and hospitalizations by age group in \nPuerto Rico , 2010 –2020\nHighest case rates occurred among children 10 –19 years old\nRyff KR, Rivera A, Rodriguez DM, Santiago GA, Medina FA, Ellis EM, Torres J, Pobutsky A, Munoz -Jordan J, Paz -Bailey G, Adams \nLE. Epidemiologic Trends of Dengue in U.S. Territories, 2010 -2020. MMWR Surveill Summ . 2023 May 19;72(4):1 -12.\n\nDengue cases and hospitalizations by age group in \nUS Virgin Islands and American Samoa , 2010 –2020\nHighest case rates occurred among children 10 –19 years old\nRyff KR, Rivera A, Rodriguez DM, Santiago GA, Medina FA, Ellis EM, Torres J, Pobutsky A, Munoz -Jordan J, Paz -Bailey G, Adams \nLE. Epidemiologic Trends of Dengue in U.S. Territories, 2010 -2020. MMWR Surveill Summ . 2023 May 19;72(4):1 -12.\nSeropositive Seronegative\n4–16 years\nChildren/Adolescents\n17–60 years\nAdultsIs dengue a problem of public health importance \nfor adults living in endemic areas?\nFatal dengue cases (N = 68) by age group in \nPuerto Rico , 2010 –2020 \nHigher mortality rates occurred among adults\n*All fatal dengue cases reported during 2010 –2020 were from Puerto Rico. No deaths were reported fro m the other territories\nRyff KR, Rivera A, Rodriguez DM, Santiago GA, Medina FA, Ellis EM, Torres J, Pobutsky A, Munoz -Jordan J, Paz -Bailey G, Adams LE. Epidemiologic Trends of Dengue in U.S. Territories, 2010 -2020. MMWR Surveill Summ . 2023 May 19;72(4):1 -12.\n\nSummary –Public Health Problem\n•Dengue is endemic in six US territories and freely associated \nstates.\n•Puerto Rico has the largest population among US territories where \ndengue is endemic.\n•The highest case and hospitalization rates occur in individuals \naged 10 –19 years.\n•The highest mortality rates occur in adults aged ≥20 years.\nPublic Health Problem\nIs the problem (dengue) of public health \nimportance?\nOptions:    ○No      ○Probably no      ○Probably yes      ○Yes       ○Varies       ○Don't know\nBenefits and Harms\nBenefits and Harms\nWhat is the overall certainty of the \ndesirable anticipated effects?\nOutcomes: desirable anticipated effects\nOutcome Importance* \nVirologically confirmed dengue due to any serotype Critical\nHospitalization for dengue due to any serotype Critical\nDengue hemorrhagic fever due to any serotype Critical\nSevere dengue (trial definition) due to any serotype Critical\n*Options are critical, important but not critical, not important for decision -making\nSystematic review\n•Systematic search identified 370 articles\n•17 met inclusion/exclusion criteria including data on outcomes of interest \nfrom phase 1 –3 trials.\n•However, 0 articles contained the 57 month follow -up time of interest \nthat has been presented to and discussed by Work Group and ACIP . \n•All vaccine efficacy and safety data provided by Takeda.*\n*One article regarding safety outcomes used in systematic review has been published (Patel, CID, 2022), but \ndata stratified by PICO populations was provided by Takeda in personal communications with WG lead.\nMultiple GRADE domains do not change for \nthe populations assessed or outcomes.\nOutcome№ of \nstudiesStudy \ndesignRisk of bias Inconsistency Indirectness ImprecisionOther \nconsiderationsCertainty\nVCD\nHospitalization\nDHF\nSevere Dengue\nIndirectness and imprecision varied by population/outcome \nassessed and determined final certainty level.\nOutcome№ of \nstudiesStudy \ndesignRisk of bias Inconsistency Indirectness ImprecisionOther \nconsiderationsCertainty\nVCD\nHospitalization\nDHF\nSevere Dengue\nSAE\nDeaths\nSeropositive Seronegative\n4–16 years\nChildren/Adolescents•Phase 3 Trial data •Phase 3 Trial data\n17–60 years\nAdultsHow certain are the desirable effects in \nchildren/adolescents?\n*Immunogenicity in seropositive adults is expected to be at least as high as in seronegative adults.\nOverall VE\n61.2% (56.0, 65.8%)\nVE in Seropositives\n64.2% (58.4, 69.2%)VE in Seronegatives\n53.5% (41.6 –62.9%)\nVE in Seropositives by Serotype\nDENV -1 56.1% (44.6, 65.2%)\nDENV -2 80.4% (73.1, 85.7%)\nDENV -3 52.3% (36.7, 64.0%)\nDENV -4 70.6% (39.9, 85.6%)VE in Seronegatives by Serotype\nDENV -1 45.4% (26.1, 59.7%)\nDENV -2 88.1% (78.6, 93.3%)\nDENV -3 -15.5% (-108.2, 35.9%)\nDENV -4 -105.6% (-628.7, 42.0%)Vaccine Efficacy* Outcome: Virologically Confirmed Dengue\n*57 months after first dose, s ignificant results bolded. Number for seropositive placebo \nparticipants 4,855 and vaccine 9,666; Seronegative placebo 1,832 and vaccine 3,714. Paz-Bailey. ACIP , February 17, 2023.\nOverall VE\n84.1% (77.8, 88.6%)\nVE in Seropositives\n85.9% (78.7, 90.7%)VE in Seronegatives\n79.3% (63.5, 88.2%)\nVE in Seropositives by Serotype\nDENV -1 66.8% (37.4, 82.3%)\nDENV -2 95.8% (89.6, 98.3%)\nDENV -3 74.0% (38.6, 89.0%)\nDENV -4 100% (NE, NE)†VE in Seronegatives by Serotype\nDENV -1 78.4% (43.9, 91.7%)\nDENV -2 100% (NE, NE)§\nDENV -3 -87.9% (-573.4, 47.6%)¶\nDENV -4 100 % (NE, NE)**Vaccine Efficacy* Outcome: Hospitalization\n†DENV -4 Placebo events: 3 TAK-003 events: 0§DENV -2 Placebo events: 23    TAK -003 events: 0\n¶DENV -3 Placebo events: 3 TAK-003 events: 11\n**DENV -4 Placebo events: 1 TAK-003 events: 0\n*57 months after first dose, s ignificant results bolded. Number for seropositive placebo \nparticipants 4,855 and vaccine 9,666; Seronegative placebo 1,832 and vaccine 3,714.Paz-Bailey. ACIP , February 17, 2023.\nOverall VE\n84.1% (77.8, 88.6%)\nVE in Seropositives\n85.9% (78.7, 90.7%)VE in Seronegatives\n79.3% (63.5, 88.2%)\nVE in Seropositives by Serotype\nDENV -1 66.8% (37.4, 82.3%)\nDENV -2 95.8% (89.6, 98.3%)\nDENV -3 74.0% (38.6, 89.0%)\nDENV -4 100% (NE, NE)†VE in Seronegatives by Serotype\nDENV -1 78.4% (43.9, 91.7%)\nDENV -2 100% (NE, NE)§\nDENV -3 -87.9% (-573.4, 47.6%)¶\nDENV -4 100 % (NE, NE)**Vaccine Efficacy* Outcome: Hospitalization\n†DENV -4 Placebo events: 3 TAK-003 events: 0§DENV -2 Placebo events: 23    TAK -003 events: 0\n¶DENV -3 Placebo events: 3 TAK-003 events: 11\n**DENV -4 Placebo events: 1 TAK-003 events: 0\n*57 months after first dose, s ignificant results bolded. Number for seropositive placebo \nparticipants 4,855 and vaccine 9,666; Seronegative placebo 1,832 and vaccine 3,714.Data insufficient to rule \nout an increased risk \nPaz-Bailey. ACIP , February 17, 2023.\nOverall VE\n70.0% (31.5, 86.9%)\nVE in Seropositives\n80.9% (46.3, 93.2%)VE in Seronegatives\n-3.4% ( -464.7, 81.1%)Dengue Hemorrhagic Fever \n(1997 Definition)\n*57 months after first dose, s ignificant results for vaccine efficacy bolded. Number for seropositive \nplacebo participants 4,855 and vaccine 9,666; Seronegative placebo 1,832 and vaccine 3,714.Overall VE\n70.2% ( -24.7, 92.9%)\nVE in Seropositives\n90.2% (16.4, 98.9%)VE in Seronegatives\n-999.0% (NE, NE)Severe Dengue\nTrial -specific Definition\nEvents by Serotype\nPlacebo TAK-003\nDENV -1 <10 <10\nDENV -2 <10 <10\nDENV -3 <10 <10\nDENV -4 <10 <10\nTotal 13 5Events by Serotype\nPlacebo TAK-003\nDENV -1 <5 <5\nDENV -2 <5 <5\nDENV -3 <5 <5\nDENV -4 <5 <5\nTotal 2 4Events by Serotype\nPlacebo TAK-003\nDENV -1 <5 <5\nDENV -2 <5 <5\nDENV -3 <5 <5\nDENV -4 <5 <5\nTotal 5 1Events by Serotype\nPlacebo TAK-003\nDENV -1 <5 <5\nDENV -2 <5 <5\nDENV -3 <5 <5\nDENV -4 <5 <5\nTotal 0 2\nPaz-Bailey. ACIP , February 17, 2023.\nOutcomes: desirable anticipated effects\nOutcome Importance* \nVirologically confirmed dengue due to any serotype Critical\nHospitalization for dengue due to any serotype Critical\nDengue hemorrhagic fever due to any serotype Critical\nSevere dengue (trial definition) due to any serotype Critical\n*Options are critical, important but not critical, not important for decision -making\nWhat is the overall certainty of the desirable anticipated \neffects in children/adolescents aged 4 –16 years?\nOutcome (Desirable) Vaccine Efficacy Imprecision Indirectness Certainty\nVirologically confirmed dengue 64.2 (58.4, 69.2) Not serious\nHospitalization 85.9 (78.7, 90.7) Not serious\nDengue hemorrhagic fever 80.9 (46.3, 93.2) Not serious\nSevere dengue (trial definition) 90.2 (16.4, 98.9) Not serious\nOutcome (Desirable) Vaccine Efficacy Imprecision Indirectness Certainty\nVirologically confirmed dengue 53.5 (41.6, 62.9) Not serious\nHospitalization 79.3 (63.5, 88.2) Not serious\nDengue hemorrhagic fever -3.4 ( -464.7, 818.1) Serious\nSevere dengue (trial definition) NE (NE, NE) SeriousSeropositive children/adolescents aged 4 –16 years\nSeronegative children/adolescents aged 4 –16 years\nDoes the study population differ \nfrom the population of interest? \nDENV -1 and DENV -2 were the most common \nserotypes in the TAK -003 Phase 3 trial.\nTakeda –ACIP WG presentation September 13th230\n193\n113\n23\n050100150200250\n1 2 3 4VCD case counts in Placebo group\nAll four serotypes have circulated in PR from \n2010 –2020 .\nRyff KR, Rivera A, Rodriguez DM, Santiago GA, Medina FA, Ellis EM, Torres J, Pobutsky A, Munoz -Jordan J, Paz -Bailey G, Adams \nLE. Epidemiologic Trends of Dengue in U.S. Territories, 2010 -2020. MMWR Surveill Summ . 2023 May 19;72(4):1 -12.\nThe VE for all serotypes combined \nfrom the phase 3 trials \ndoes notdirectly apply to our \npopulation of interest and their \nfuture risk of dengue if \nit does not protect against one or \nmore of the 4 serotypes. VE in Seropositives\n80.9%    (46.3, 93.2%)\nVE by Serotype\nDENV -1\nDENV -2\nDENV -3\nDENV -4\n\nThe VE for all serotypes combined \nfrom the phase 3 trials \nis only directly applicable to our \npopulation of interest and their \nfuture risk of dengue if there is\nsignificant protection against all 4 \nserotypes. VE in Seropositives\n80.9%    (46.3, 93.2%)\nVE by Serotype\nDENV -1\nDENV -2\nDENV -3\nDENV -4\nWhat is the overall certainty of the desirable anticipated \neffects in children/adolescents aged 4 –16 years?\nOutcome (Desirable) Vaccine Efficacy Imprecision Indirectness Certainty\nVirologically confirmed dengue 64.2 (58.4, 69.2) Not serious Not serious High\nHospitalization 85.9 (78.7, 90.7) Not serious Not serious High\nDengue hemorrhagic fever 80.9 (46.3, 93.2) Not serious Serious Moderate\nSevere dengue (trial definition) 90.2 (16.4, 98.9) Not serious Serious Moderate\nOutcome (Desirable) Vaccine Efficacy Imprecision Indirectness Certainty\nVirologically confirmed dengue 53.5 (41.6, 62.9) Not serious Serious Moderate\nHospitalization 79.3 (63.5, 88.2) Not serious Serious Moderate\nDengue hemorrhagic fever -3.4 ( -464.7, 818.1) Serious Serious Low\nSevere dengue (trial definition) NE (NE, NE) Serious Serious LowSeropositive children/adolescents aged 4 –16 years\nSeronegative children/adolescents aged 4 –16 years\nSeropositive Seronegative\n4–16 years\nChildren/Adolescents\n17–60 years\nAdults•Outcomes assessed through \nimmunobridgingHow certain are the desirable effects in \nadults?\nGMR DENV -1 6 months 607 353 0.62 (0.51, 0.76) Yes\nGMR DENV -2 6 months 607 355 0.66 (0.57, 0.76) Yes\nGMR DENV -3 6 months 607 355 0.98 (0.84, 1.14) Yes\nGMR DENV -4 6 months 607 354 1.01 (0.86, 1.18) YesAntibody titers in seronegative adults (18 –60) were \nnoninferior* at 1 and 6 months for almost all serotypes \ncompared to participants aged 4 –16.\nOutcome (desirable) Time after 2nd\ndoseN (4–16 \nyears)N (18–60 \nyears)Geometric Mean Ratio Met noninferiority \nobjective*\nGMR DENV -1 1 month 641 367 0.69 (0.58, 0.82) Yes\nGMR DENV -2 1 month 641 367 0.59 (0.52, 0.66) Yes\nGMR DENV -3 1 month 641 367 1.77 (1.53, 2.04) No\nGMR DENV -4 1 month 641 367 1.05 (0.92, 1.20) Yes\n*Non -inferiority was defined as a geometric mean ratio (GMR) with the upper bound of the 95% CI below 2.0.\nRivera L, Biswal S, Sáez -Llorens X, Reynales H, López -Medina E, Borja -Tabora C, et al. Three years \nefficacy and safety of Takeda's dengue vaccine candidate (TAK -003). Clin Infect Dis. 2021 Oct 4.\nWhat is the overall certainty of the desirable \nanticipated effects in adults aged 17 –60 years?\nOutcome (Desirable) N (4–16 \nyears)N (18–60 \nyears)Met noninferiority \nobjectiveIndirectness Certainty\nVCD, hospitalization, \nDHF, severe dengue \n(assessed with \nimmunobridging )607-641 353-367 Yes for all serotypes, \nexcept for DENV -3 \nassessed at 1 monthSerious* ModerateSeronegative adults aged 17 –60 years\n*Downgraded once for indirectness due to immunobridging.\nSeropositive Seronegative\n4–16 years\nChildren/Adolescents\n17–60 years\nAdults•Outcomes assessed through \nimmunobridging in \nseronegatives *•Outcomes assessed through \nimmunobridgingHow certain are the desirable effects in \nadults?\n*Immunogenicity in seropositive adults expected to be at least as robust as in seronegative adults; downgraded twice for indi rectness.\nWhat is the overall certainty of the desirable \nanticipated effects in adults aged 17 –60 years?\nOutcome (Desirable) N (4–16 \nyears)N (18–60 \nyears)Met noninferiority \nobjectiveIndirectness Certainty\nVCD, hospitalization, \nDHF, severe dengue \n(assessed with \nimmunobridging )607-641 353-367 Yes for all serotypes, \nexcept for DENV -3 \nassessed at 1 monthSerious ModerateSeronegative adults aged 17 –60 years\nOutcome (Desirable) Indirectness Certainty\nVCD, hospitalization, DHF, severe dengue (assessed with \nimmunobridging in seronegative adults)Very Serious* LowSeropositive adults aged 17 –60 years\n*Downgraded twice for indirectness, because outcomes are assessed with immunobridging data from seronegative \nadults and assumption of equal or greater immunogenicity in seropositive adults \nSeropositives Seronegatives\n4–16 years\nChildren/Adolescents\n17–60 years\nAdultsSummary of Desirable Outcomes\nOutcome VE Certainty\nVCD 64.2 (58.4, 69.2) High\nHospitalization 85.9 (78.7, 90.7) High\nDHF 80.9 (46.3, 93.2) Moderate\nSevere dengue 90.2 (16.4, 98.9) Moderate\nOutcome (Desirable) Certainty\nAll outcomes\n(assessed with \nimmunobridging )ModerateOutcome (Desirable) Certainty\nAll outcomes\n(assessed with immunobridging in \nseronegatives *)Low\n*Immunogenicity in seropositive adults is expected to be at least as high as in seronegative adults.Outcome VE Certainty\nVCD 53.5 (41.6, 62.9) Moderate\nHospitalization 79.3 (63.5, 88.2) Moderate\nDHF -3.4 ( -464.7, 818.1) Low\nSevere dengue NE  (NE, NE) Low\nSeropositives Seronegatives\n4–16 years\nChildren/Adolescents\n17–60 years\nAdultsSummary of Certainty for All Desirable Outcomes\n*Immunogenicity in seropositive adults is expected to be at least as high as in seronegative adults.High –Moderate Moderate –Low\nModerate Low\nBenefits and Harms\nHow substantial are the desirable \nanticipated effects?\nThe population level effects of TAK -003 \nimplementation will vary by…\nseroprevalence of past infection        AND serotype circulation.\nAnti-DENV IgG\n1 2 3 4\nPreliminary Modeled Estimates of Population -\nlevel Impacts in San Juan, PR* over 10 years\nRecommendation Reduction in VCD† Reduction in hospitalizations†\n4–16, seropositive ( screening‡) 1% 3%\n4–16, all serostatuses (no screening) 3% 3%\n17–60, seropositive ( screening‡) 6% 10%\n17–60, all serostatuses (no screening) 8% 13%\n4–60, seropositive ( screening‡) 7% 12%\n4–60, all serostatuses (no screening) 9% 15%\nEspaña . ACIP , June 22, 2023.*The model assumes a seroprevalence of 40% at age 9, a vaccine coverage increasing from 0 to 40% over 10 years in all ages el igible, and \nserotype distribution simulated from 20 years of historical data (1996 –2016) from San Juan, Puerto Rico (PR).\n†Averted symptomatic and hospitalizations are for all ages in San Juan and include direct and indirect effects. \n‡Screening test with 80% sensitivity and 98% specificity\nSummary of Desirable Anticipated Effects\n•Modeling* shows a reduction in VCD and hospitalizations following \nimplementation of TAK -003 in all populations explored in the policy \nquestions.\n•Reductions in VCD and hospitalizations are higher when vaccination is \nimplemented in broader age ranges and for both seropositive and \nseronegative individuals. \n*Model based on preliminary data from Dr. España presented to ACIP on June 22, 2023.\nBenefits and Harms\nHow substantial are the desirable \nanticipated effects?\nOptions:    ○Minimal     ○Small    ○Moderate     ○Large      ○Varies       ○Don't know\nBenefits and Harms\nHow substantial are the undesirable \nanticipated effects?\nWhat is the overall certainty?\nOutcomes: undesirable anticipated effects\nOutcome Importance* \nSerious adverse events (SAEs) Critical\nDeaths Critical\nSystemic reactions†Important\nLocal reactions†Important\nInterference with co -administered vaccines†Important\n*Options are critical , important but not critical, not important for decision -making\n†Not assessed in GRADE analysis\nSeropositive Seronegative\n4–16 years\nChildren/Adolescents•Phase 2 and 3 trials •Phase 2 and 3 trials\n17–60 years\nAdultsHow certain are the undesirable effects in \nchildren/adolescents?\n*Immunogenicity in seropositive adults is expected to be at least as high as in seronegative adults.\nWhat is the overall certainty of the undesirable anticipated \neffects in children/adolescents aged 4 –16 years?\nSeropositive children/adolescents aged 4 –16 years\nSeronegative children/adolescents aged 4 –16 yearsOutcome \n(Undesirable)n/N TAK -003 n/N placebo Hazard Ratio Imprecision Indirectness Certainty\nSAEs 826/9725 (8.5%) 503/4944 (10.2%)* 0.82 (0.74, 0.92) Not serious Not serious High\nDeaths† 14/9725 (0.14%) 6/4944 (0.12%) 1.18 (0.45, 3.07) Not serious Not serious High\nOutcome \n(Undesirable)n/N TAK -003 n/N placebo Hazard Ratio Imprecision Indirectness Certainty\nSAEs 323/3984 (8.1%) 183/1979 (9.3%)*0.88 (0.73, 1.05) Not serious Not serious High\nDeaths† 2/3984 (0.05%) 1/1979 (0.05%) 1.00 (0.09, 11.04) Not serious Not serious High\n*Higher dengue SAEs in placebo (n=100) compared to TAK -003 (n=51) resulted in HR <1 for all SAEs in TAK -003 compared to placebo.\n†None of the deaths in the trial were due to dengueCommunication with Takeda. April 25, 2023.\nSeropositive Seronegative\n4–16 years\nChildren/Adolescents•Phase 2 and 3 trials •Phase 2 and 3 trials\n17–60 years\nAdults•Phase 2 and 3 trials •Phase 2 and 3 trialsHow certain are the undesirable effects in \nadults?\nWhat is the overall certainty of the undesirable \nanticipated effects in adults aged 17 –60 years?\nSeronegative adults aged 17 –60 years\nSeropositive adults aged 17 –60 yearsOutcome \n(Undesirable)n/N TAK -003 n/N placebo Hazard Ratio Imprecision Indirectness Certainty\nSAEs 9/488 (1.8%) 3/84 (3.6%) 0.499 (0.14, 1.84) Not serious Not serious High\nDeaths 0/488 0/84 N/A Not serious Not serious High\nOutcome \n(Undesirable)n/N TAK -003 n/N placebo Hazard Ratio Imprecision Indirectness Certainty\nSAEs 3/83 (3.6%) 0/31 N/A Serious Not serious Moderate\nDeaths 0/83 0/31 N/A Serious Not serious Moderate\nCommunication with Takeda. April 25, 2023.\nSeropositives Seronegatives\n4–16 years\nChildren/Adolescents\n17–60 years\nAdultsSummary of Undesirable Outcomes Certainty\nOutcome \n(Undesirable)n/N TAK -003 n/N placebo Certainty\nSAEs 3/83 (3.6%) 0/31 Moderate\nDeaths 0/83 0/31 ModerateOutcome \n(Undesirable)n/N TAK -003 n/N placebo Certainty\nSAEs 826/9725 \n(8.5%)503/4944 \n(10.2%)High\nDeaths 14/9725 \n(0.14%)6/4944 \n(0.12%)HighOutcome \n(Undesirable)n/N TAK -003 n/N placebo Certainty\nSAEs 323/3984 \n(8.1%)183/1979 \n(9.3%)*High\nDeaths 2/3984 \n(0.05%)1/1979 \n(0.05%)High\nOutcome \n(Undesirable)n/N TAK -003* n/N placebo Certainty\nSAEs 9/488 (1.8%) 3/85 (3.6%) High\nDeaths 0/488 0/85 High\nSeropositives Seronegatives\n4–16 years\nChildren/Adolescents\n17–60 years\nAdultsSummary of Certainty for All Undesirable Outcomes\nHigh High\nHigh Moderate\nDengue vaccine outcomes of interest can be a \ndesirable and an undesirable outcome.\nDesirable Effects Undesirable EffectsPrevent Dengue Enhance Dengue?\nDesirable Effects Undesirable EffectsSeropositives\nDENV -1\nDENV -2\nDENV -3\nDENV -4Seronegatives\nDENV -1\nDENV -2Prevent Dengue\nSeronegatives\nDENV -3*The effects differ by vaccinee serostatus \nand serotype.\n“Data insufficient to \nrule out an increased \nrisk among vaccine \nrecipients.”\n*for outcome of hospitalization.Enhance Dengue?\nBenefits and Harms\nDo the desirable effects outweigh the \nundesirable effects?\n*Hospitalizations among vaccinees in a no screening scenario represent hospitalizations among seronegative persons who are in fected by \nDENV -3 post -vaccination. In the screening scenario, they represent hospitalizations among seronegative persons with false positi ve test results \nwho are infected with DENV -3 and are subsequently hospitalized. Model based on 40% seroprevalence at 9 years old. Other model \nassumptions described by Dr. España (ACIP , June 22, 2023).Screening decreased the ratio of averted to additional hospitalizations compared to no pre -\nvaccination screening but may lead to lower absolute hospitalizations averted. \n0102030405060708090100\n1 2 3Ratio ofhospitalizations averted to\nadditional hospitalizations *\n6:115:135:1\n18:1102:1\n69:1\nSummary of Balance of Desirable and \nUndesirable Anticipated Effects\n•Modeling* shows that the ratio of hospitalizations averted to additional \nhospitalizations caused by vaccination increases with screening and \nvaccination of seropositive individuals only.\n•This ratio is higher in the population aged 17 –60 years compared to the \npopulation aged 4 –16 years under both screening and no screening \nscenarios.\n•The benefits of screening and vaccinating seropositive individuals will be \nweighed against the lower overall reduction in VCD and hospitalizations in \nthis scenario.\n*Models based on preliminary data from Dr. España presented to ACIP on June 22, 2023.\nBenefits and Harms\nDo the desirable effects outweigh the \nundesirable effects?\nOptions: ○Favors intervention   ○Favors comparison   ○Favors both   ○Favors neither  ○Varies   ○Don't know \nResource Use\nIs the intervention a reasonable and \nefficient allocation of resources?\nPreliminary Modeled Estimates of Cost -\neffectiveness in San Juan, PR over 10 years\nPopulation and Strategy†ICER per hospitalization \naverted (USD)§ICER per QALY gained (USD)§¶\n4–16 (screening) 16,800 181,918\n4–16 (no screening) 46,813 254,751\n17–60 (screening) 48,989 396,574\n17–60 (no screening) 39,886 314,597\n4–60 (screening) 48,305 384,830\n4–60 (no screening) 45,495 326,412\nEspaña . ACIP , June 22, 2023.Estimates modeled on San Juan, PR, population 326,953. Puerto Rico has a total population of 3.264 million) (US Census Bureau ). For estimates with screening, the model assumes \na test with 80% sensitivity and 98% specificity.\n†The model assumes a seroprevalence of 40% at age 9 and a vaccine coverage increasing from 0 to 40% over 10 years. \n§Cost of full vaccination was $330 US; cost of a test was $30 with annual retesting for negative individuals.\n¶ICER per QALY gained was modeled from a societal perspective with a 3% discounting rate. \nResource Use\nIs the intervention a reasonable and \nefficient allocation of resources?\nOptions:    ○No      ○Probably no      ○Probably yes      ○Yes       ○Varies       ○Don't know\nSummary\n•Presented 3 of 7 EtRdomains:\n•Public Health Problem\n•Benefits and Harms\n•Resource Use\n•Certainty assessment of the evidence for outcomes by policy question \nranged from high to low .\n•Weighing the risks and benefits of dengue vaccination is complex.\n•Work Group discussions will continue this summer.\n•Draft recommendation and vote will occur at the next meeting .\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the \nofficial position of the Centers for Disease Control and Prevention.\nACIP Members\nWilbur Chen (Chair)\nKathy Poehling\nBeth Bell\nVeronica McNally\nCDC Co -Leads\nGabriela Paz -Bailey\nLaura Adams\nEx Officio Members\nKaitlyn Morabito (NIH)\nRalph LeBlanc (FDA)\nIhid Carneiro Leao (FDA)\nKirk Prutzman (FDA)\nSrihari Seshadri (DOD)\nLiaison Representatives\nElizabeth Barnett (AAP)\nRob Schechter (AIM)Consultants\nEdwin Asturias\nRobert Atmar\nAlan Barrett\nIrisCardona\nAnna Durbin\nTony Marfin\nKristen Pierce\nAnita Shet\nCDC Contributors\nJoshua Wong\nNicole Medina\nMimi Eckert\nRachel Eidex\nAlfonso Hernandez\nSusan Hills\nTerri Hyde\nMike McNeilJorge Munoz\nErin Staples\nCindy Weinbaum\nRita Helfand\nGRADE Consultants\nDoug Campos -Outcalt\nRebecca Morgan\nGRADE Analysis Team\nJoshua Wong (Co -lead)\nAlfonso Hernandez (Co -Lead)\nCameron Adams\nArlene Rivera\nDaniel MilanQuestions?ACIP Dengue Vaccines Workgroup and Support Team", "summary": "Centers for Disease Control and Prevention National Center for Emerging and Zoonotic Infectious Diseases Partial Evidence to Recommendations  Framework for Dengue Vaccine TAK -003 Joshua Wong, MD ACIP June 22, 2023 Dengue Branch, CDC  Goals for Partial EtRPresentation •Summarize the extent of the Work Group deliberations to date •Present three Evidence to Recommendations ( EtR) domains* •Prepare ACIP for the next meeting which will include a full EtRpresentation,  proposed recommendation, and…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/05-Dengue-Wong-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 65}
{"title": "01 Chikungunya Bell 508", "content": "CHIKUNGUNYA VACCINES\nBeth Bell, MD, MPH\nChair, ACIP Chikungunya Vaccines Work GroupACIP Meeting\nJune 22, 2023\nBackground\nIn February 2023, FDA accepted Valneva’s Biologics License Application \n(BLA) for their chikungunya vaccine and granted priority review, with \nlicensure possible in August 2023\nNo chikungunya vaccine ever licensed in United States or globally\nNo existing ACIP chikungunya vaccine recommendations\nChikungunya Vaccines Work Group is developing policy options for ACIP’s \nconsideration for use of chikungunya vaccine among U.S. persons at risk of \nchikungunya, including \n–Travelers\n–Laboratory workers\n–Residents of U.S. territories and states with, or at risk of, transmission\nRecap of previous Work Group presentations to ACIP \nOctober 2022\n–Overview of chikungunya virus disease and vaccines\n–Immunogenicity and safety of Valneva’s chikungunya vaccine\nFebruary 2023\n–Global epidemiology of chikungunya\n–Chikungunya among U.S. travelers\n–Persistent arthralgia following chikungunya\nOverview of today’s session\nValue and preferences for chikungunya vaccine among U.S. travelers and \nhealthcare providers\n–Ms. Nicole Lindsey (CDC/NCEZID)\nChikungunya virus infection among laboratory workers\n–Dr. Susan Hills (CDC/NCEZID)\nUpdate and observations on large chikungunya outbreak in Paraguay\n–Dr. Susan Hills (CDC/NCEZID)\nPlans and timelines for Work Group activities\n–Dr. Susan Hills (CDC/NCEZID)\nACIP Ex Officio Invited Consultants\nBeth Bell, Univ Washington (Chair) Robin Levis, FDA Alan Barrett, Univ Texas Galveston\nWilbur Chen, Univ Maryland Sixun Yang, FDA Carina Blackmore, Florida Dept Health\nLesley Dupuy, NIH Alan Lam, DoD\nCDC Leads Margaret Ryan, DoD\nSusan Hills, DVBD (Lead) ACIP Liaisons Steven Schofield, CATMAT\nNicole Lindsey, DVBD (Deputy Lead) Elizabeth Barnett, ISTM David Shlim, Jackson Hole Travel & Trop Med\nJames Campbell, AAP Nestor Sosa, Uni New Mexico Hospital\nMary Pat Friedlander, AAFP Sanet Torres, San Jorge Children & Women's Hospital\nKirsten Vannice, Bill & Melinda Gates FoundationMary Wilson, Univ California San FranciscoChikungunya Vaccines Work Group members\nDVBD DGMQ ISD\nErin Staples Sarah Guagliardo Elisabeth Velazque z\nAnn Powers\nLaura Adams DHQP GRADE/ETR consultants\nJoshua Wong Michael McNeil Doug Campos -Outcalt\nRebecca Morgan\nNCEZID GID\nRita Helfand Rebecca Casey ACIP Secretariat\nJessica MacNeil, NCIRD\nLeslie Lee, NCIRDChikungunya Vaccines Work Group CDC participants", "summary": "CHIKUNGUNYA VACCINES Beth Bell, MD, MPH Chair, ACIP Chikungunya Vaccines Work GroupACIP Meeting June 22, 2023 Background In February 2023, FDA accepted Valneva’s Biologics License Application  (BLA) for their chikungunya vaccine and granted priority review, with  licensure possible in August 2023 No chikungunya vaccine ever licensed in United States or globally No existing ACIP chikungunya vaccine recommendations Chikungunya Vaccines Work Group is developing policy options for ACIP’s …", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/01-Chikungunya-Bell-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 6}
{"title": "02 Chikungunya Lindsey 508", "content": "National Center for Emerging and Zoonotic Infectious Diseases\nValue of a vaccine to prevent travel -related \nchikungunya for US persons\nNicole Lindsey, MS\nCDC Deputy Lead , Chikungunya Vaccines Work Group\nArboviral Diseases Branch\nCenters for Disease Control and PreventionJune 22, 2023\nPotential value of a chikungunya vaccine among \ninternational travelers (Valneva survey)\n2021 online survey of 2,002 US residents aged ≥ 18 years who either \ntravelled internationally in last 3 years or planned to do so in next 3 years\n–Excluded anyone who self -identified as ‘anti -vaccination’\nLimited information provided about the surveyed population\nParticipants provided basic information about chikungunya disease\n–Disease distribution, symptoms of disease, rarely joint pain/fatigue that lasts \nfor months or years, and lack of treatment\n–No information on risk of infection, potential adverse events, costs of vaccineAwareness of chikungunya and value of a chikungunya \nvaccine among travelers\n9\nOnly 18% had heard of chikungunya prior to survey\nAfter participants provided information about chikungunya, asked two \nquestions:\n–How likely would you be to ask a healthcare professional about a vaccine to \nprotect yourself against chikungunya? 72% Likely \n–If a doctor or health care provider recommended the chikungunya vaccine for you, how likely would you be to get vaccinated?   81% LikelyAwareness of chikungunya and value of a chikungunya \nvaccine among travelers\n10\nLow awareness of chikungunya virus disease among traveler population\nMost would likely ask healthcare provider about a chikungunya vaccine \nand be vaccinated if their provider recommended vaccination\nLimitations\n–No info rmation provided to participants about risk of disease or \nrisks/benefits of vaccination\n–No information about co sts\n–Although traveler population, unknown if representative of traveler \npopulation to areas at risk for chikungunyaAwareness of chikungunya and value of a chikungunya \nvaccine among travelers: Summary\n11\nPotential value of a chikungunya vaccine among U.S. \npersons (CDC survey) \nMethod: Porter Novelli Consumer Styles surveys\nOnline panel representative of non -institutionalized U.S. population  \n–Members randomly recruited using probability -based sampling by address \n–Provided with a laptop or tablet and access to internet if needed\n–Receive small monetary rewards for participation\n2022 Summer Styles respondents included 4,156 invited adults (69% \nresponse rate)\nCore questions capture demographic information in addition to consumer attitudes, values, and behaviors\nData weighted to U.S. Population Survey proportions for sex, age, household income, race/ethnicity, household size, education, census region\n13\nQuestions on value of a chikungunya vaccine\n1.Imagine you are going on a trip to another country. You have a 1 in 150 \nchance of getting a disease. About 1 in 4 people who get the disease \nsuffer from long -term joint pain. A vaccine is available that costs $350 \nand is not covered by insurance. How likely would you be to get the \nvaccine? \n2.Now imagine you are going on the same trip, but your chances are 1 in \n15,000 of getting the disease. About 1 in 4 people who get the disease \nsuffer from long -term joint pain. The vaccine costs $350 and is not \ncovered by insurance. How likely would you be to get the vaccine? \n3.Which factors are most important to you in deciding whether or not to get the vaccine? \n14\n50% female; median age 54 years (range: 18- 94 years)\n72% identified as white, non- Hispanic\nEducation\n–5% with less than high school education\n–25% with high school education\n–70% with at least some college or higher education\nHousehold income\n–<$25K: 10%\n–$25- <$75K: 30%\n–≥$75K: 60% Demographics of survey participants (N=4,156)\n15\nImagine you are going on a trip \nto another country. You have a \n1 in 150 chance of getting a \ndisease. About 1 in 4 people who get the disease suffer from \nlong -term joint pain. A vaccine \nis available that costs $350 and is not covered by insurance. How likely would you be to get \nthe vaccine? (n=4,146)\n*Includes very and somewhat likely responses\n**Includes very and somewhat unlikely responses42%\n26%32%\nLikely* Unsure Unlikely**\n16\nLikelihood of chikungunya vaccination by age group \nwhere disease risk is 1 in 150 \n45%43%43%35%\n26%26%24%28%\n30%31%33%37%\n70+50-6930-4918-29\nLikely Not Sure Unlikely\n17\nLikelihood of chikungunya vaccination by sex where \ndisease risk is 1 in 150 \n39%44%\n29%22%\n32%33%\nFemaleMale\nLikely Not Sure Unlikely\n18\nLikelihood of chikungunya vaccination by \nrace/ethnicity where disease risk is 1 in 150 \n51%42%36%42%\n26%21%35%25%\n24%37%29%33%\nOtherHispanicBlackWhite\nLikely Not Sure Unlikely\n19\nLikelihood of chikungunya vaccination by education \nwhere disease risk is 1 in 150 \n54%41%31%\n19%26%32%\n27%33%38%\nCollege and higherSome collegeHigh school or less\nLikely Not Sure Unlikely\n20\nLikelihood of chikungunya vaccination by household \nincome where disease risk is 1 in 150 \n51%38%31%22%\n22%29%27%36%\n27%33%42%42%\n75K+50-74K25-49K<25K\nLikely Not Sure Unlikely\n21\nLikelihood of chikungunya vaccination where disease \nrisk is 1 in 150: Summary\n42% respondents likely to be vaccinated when disease risk is high\n–About a third unlikely to be vaccinated even in high -risk scenario\n–About a quarter unsure\nMain differences by group\n–Lower likelihood of vaccination among youngest age groups, those with lower \neducation and household income levels\n–Blacks less likely to be vaccinated and more likely to report ‘unsure’\n22\nNow imagine you are going on \nthe same trip, but your \nchances are 1 in 15,000 of \ngetting the disease. About 1 in 4 people who get the disease \nsuffer from long -term joint \npain. A vaccine is available that \ncosts $350 and is not covered \nby insurance. How likely would \nyou be to get the vaccine? \n(n=4,138)27%\n24%49%\nLikely* Unsure Unlikely**\n*Includes very and somewhat likely responses\n**Includes very and somewhat unlikely responses 23\nLikelihood of chikungunya vaccination where disease \nrisk is 1 in 15,000: Summary\nLevel of risk is important factor in determining likelihood of vaccination \nwith 27% being likely to vaccinate in low -risk scenario compared to 42% in \nhigher risk scenario\nAbout a quarter of respondents unsure for both risk level scenarios\nSimilar trends for different demographic factors between high and low risk scenarios, with responses more towards ‘unlikely’ end of scale\n24\nWhich factors are most important to you in deciding \nwhether or not to get the vaccine? (n=4,130)\n6%11%36%41%43%57%\nI do not get any vaccinationsOther factors not listedChance of getting long-term joint painCost of the vaccineChance of side effects from the vaccineChance of getting the disease\n25\nNot many differences by age \n–Youngest age group more concerned about costs and less about long -term \njoint pain\n–Middle aged (45 -59 years) most concerned about vaccine side effects\nNo meaningful differences by sex or race/ethnicity\nImportance of risk of disease and risk of long -term joint pain following \ninfection increased with both education level and household income\nConversely, proportion of respondents that do not receive vaccination \ndecreased by increasing education and incomeDifferences in factors influencing vaccination by \ndemographics\n26\nFactors influencing vaccination in high- risk scenario \nby likelihood of vaccination\n71%\n51%\n40%\n33%\n1%44%\n21%42%51%\n14%\nChance of getting\ndiseaseChance of long-term\njoint painChance of side\neffects from vaccineCost of the vaccine I do not get any\nvaccinationsLikely\nUnlikely\n27\nFactors influencing vaccination in lower risk scenario \nby vaccine acceptance\n68%\n53%\n40%\n27%\n1%55%\n28%43%51%\n9%\nChance of getting\ndiseaseChance of long-term\njoint painChance of side\neffects from vaccineCost of the vaccine I do not get any\nvaccinationsLikely\nUnlikely\n28\nFactors influencing likelihood of vaccination: \nSummary\nMost commonly reported factor was risk of getting disease, which is \nconsistent with findings for high and low risk scenario questions\nAlso important are risk of side effects, vaccine cost, and risk of long -term \njoin pain following infection \nSignificant differences between those likely and unlikely to be vaccinated in importance of factors, with exception of concern about side effects\n–For “likely to be vaccinated” key factors were chance of disease and chance of \nlong -term joint pain\n–For “unlikely to be vaccinated”, key factors were vaccine cost and chance of disease \n29\nSurvey limitations\nNot a traveler population\n–Unknown how well these responses reflect attitudes of a traveler population\nOnly very basic disease information provided\nNo information on likelihood or type of side effects from vaccination\nVaccine cost was estimate based on typical travel vaccine not actual cost\n30\nPotential value of a chikungunya vaccine among U.S. \npersons: Summary\n42% of respondents likely to be vaccinated when disease risk is high; 27% \nwhen disease risk is low\n–About a quarter of participants were unsure in both scenarios\nLower likelihoods of vaccination than reported in Valenva survey (81%), \nbut were important differences in methods \n–Traveler vs general population\n–Different background information provided – more general information on \nchikungunya vs. information focusing on disease risks, sequela, and costs\n–Response to question on “likelihood of getting vaccine if recommended by \nhealthcare provider” vs “likelihood of getting vaccine” \n31\nAwareness of chikungunya and value of a \nchikungunya vaccine to U.S. travel healthcare \nproviders (Valenva survey)\nOnline survey conducted in 2021 of 158 US travel healthcare providers\n–All participants routinely preform pre -travel health counseling and prescribe \nand/or administer relevant travel vaccines\n–Mix of provider types and practice settings relevant to travel health\nHow familiar, if at all, are you with chikungunya disease? \n–Familiar with disease and have clinical knowledge of it (30%)\n–Have heard of it but don’t know what it is (20%) \n–Majority not familiar (51%)Awareness of chikungunya and value of a vaccine to \nU.S. travel healthcare providers\n33\nValue of chikungunya vaccine to U.S. travel \nhealthcare providers\nParticipants provided information:\n–Disease epidemiology, clinical presentation, types and duration of sequelae\n–Chikungunya vaccines likely available within few years\nAsked to indicate likelihood to recommend/prescribe a vaccine for \nchikungunya if recommended by ACIP\n–15% Very likely\n–73% Somewhat likely–11% Neither likely nor unlikely\n–1% Unlikely\n34\nLow awareness of and familiarity with chikungunya among U.S. healthcare \nproviders, even among those who work in travel medicine\nFollowing minimal education, 88% of providers surveyed would be likely to  recommend/administer vaccine to travelers if recommended by ACIP\n–Explicit in question that vaccination would be recommended by ACIP\n–No estimates of risk of disease or possible risks of vaccination Awareness of chikungunya and value of a vaccine to \nU.S. travel healthcare providers: Summary\n35\nValue of chikungunya vaccine to U.S. travelers and \nhealthcare providers: Summary \nAwareness of chikungunya low among travelers and healthcare providers\nHealthcare providers likely to prescribe vaccination as recommended by \nACIP and travelers interested in vaccination if recommended by provider\nIndependent of healthcare provider recommendation, about 30– 40% of \nU.S. persons interested in vaccination and remainder unsure or unlikely to \nbe vaccinated\n–Variability in population perception of whether potential desirable effects \noutweigh undesirable effects\n–Risk of disease, vaccine cost, vaccine side effects, and risk of chronic arthralgia are influential factors in deciding on chikungunya vaccination \n36", "summary": "National Center for Emerging and Zoonotic Infectious Diseases Value of a vaccine to prevent travel -related  chikungunya for US persons Nicole Lindsey, MS CDC Deputy Lead , Chikungunya Vaccines Work Group Arboviral Diseases Branch Centers for Disease Control and PreventionJune 22, 2023 Potential value of a chikungunya vaccine among  international travelers (Valneva survey) 2021 online survey of 2,002 US residents aged ≥ 18 years who either  travelled internationally in last 3 years or planned…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/02-Chikungunya-Lindsey-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 30}
{"title": "03 Chikungunya Hills 508", "content": "National Center for Emerging and Zoonotic Infectious Diseases\nCHIKUNGUNYA VIRUS INFECTIONS \nAMONG LABORATORY WORKERS\nSusan Hills, MBBS, MTH\nCDC Lead , Chikungunya Vaccines Work Group\nArboviral Diseases Branch\nDivision of Vector -Borne Diseases\nFort Collins, Colorado\nACIP meeting, June 22, 2023\nChikungunya virus management in the laboratory\nHandled at biosafety level (BSL) -3 \nHigh viral loads in blood samples increase risk for \nl\naboratory -acquired infections1\n1. Simmons G et al, Emerg Infect Dis 2016; Appassakij H et al, Transfusion 2013\n2\nInformation on laboratory worker infections\nSummary article published in 1980 by Subcommittee on \nArb\novirus Laboratory Safety (SALS)1\nCase report in a publication on exposures to pathogens in a U\n.S. laboratory2\nCases reported to the U.S. national arboviral disease s\nurveillance system\n1.The Subcommittee on Arbovirus Laboratory Safety of the American Committee on Arthropod -B orne Viruses. Am J Trop Med Hyg 1980\n2.Rusnak JM, et al. J O ccup Environ Med 2004 3\nSALS report1\nMethods\n–Conducted literature review and two surveys\n–Surveys sent to national and international labs in 1976 and 1978\n39 chikungunya virus disease cases or infections\n–38 (97%) disease cases, no deaths\n–1 (3%) asymptomatic infection\nRoute of transmission\n–7 (18%) aerosol\n–32 (82%) not identified/unknown\n1. The Subcommittee on Arbovirus Laboratory Safety of the American Committee on Arthropod -Borne Viruses. Am J Trop Med Hyg 1980\n4\nCase report from worker in a U.S. laboratory\nOccurred during 1989 –2002 \nNeedlestick injury \nFull recovery after slow convalescence with intermittent joint \np\nains, headaches, and blurred vision for several months\nRusnak JM, et al. J Occup Environ Med 20045\nReports to national arboviral disease surveillance \nsystem, 2015 –2022 \nFour disease cases\n–One case hospitalized for observation\n–No deaths \nRoute of transmission\n–Needlestick (n=2)\n–Other percutaneous (n=1)\n–Unknown (n=1) \nPhoto credit: Getty Images\n6\nReported cases likely underrepresent all infections in \nlaboratory workers\nUnderreporting of cases to national arboviral disease surveillance system\nAsymptomatic infections not reportable to surveillance system\nNo formal laboratory surveillance system\nReluctance to publish\n7\nSummary\nLaboratory workers at risk for chikungunya virus infections \na\nnd disease\n–At least 44 reports, including 4 cases during last 8 years\nDocumented modes of transmission include aerosol and pe\nrcutaneous routes\nLikelihood of disease vs. asymptomatic infection probably h\nigh\n8\nThank you\nGetty \nImages", "summary": "National Center for Emerging and Zoonotic Infectious Diseases CHIKUNGUNYA VIRUS INFECTIONS  AMONG LABORATORY WORKERS Susan Hills, MBBS, MTH CDC Lead , Chikungunya Vaccines Work Group Arboviral Diseases Branch Division of Vector -Borne Diseases Fort Collins, Colorado ACIP meeting, June 22, 2023 Chikungunya virus management in the laboratory Handled at biosafety level (BSL) -3  High viral loads in blood samples increase risk for  l aboratory -acquired infections1 1. Simmons G et al, Emerg…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/03-Chikungunya-Hills-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 9}
{"title": "04 Chikungunya Hills 508", "content": "National Center for Emerging and Zoonotic Infectious Diseases\nUPDATE AND OBSERVATIONS ON A LARGE \nCHIKUNGUNYA OUTBREAK IN PARAGUAY\nSusan Hills, MBBS, MTH\nCDC Lead , Chikungunya Vaccines Work Group\nArboviral Diseases Branch\nDivision of Vector -Borne Diseases\nFort Collins, Colorado\nACIP meeting, June 22, 2023\nChikungunya notifications*\nOctober 1, 2022 –June 3, 2023\n167,239 cases\nSource: Ministry of Public Health and Social Welfare, Paraguay\nEpidemiologic weekNo. notifications\n*Confirmed and probable cases and suspected arboviral infection 11\nChikungunya notifications* \nby district\nJanuary 1 –June 3, 2023\nSource: Ministry of Public Health and Social Welfare, Paraguay\nNo cases\n<200 cases200– 1,000 cases\n1,001– 4,000 cases\n4,001– 8,000 cases\n19,324 cases\n*Confirmed and probable cases and suspected arboviral infection12\nMorbidity and mortality among persons with probable or \nconfirmed chikungunya (N=90,709)\n~8,600 (9%) hospitalizations *\n*As of June 3, 2023263 (<1%) deaths *\n13\nChikungunya virus transmission in 2023\nin new areas of South America\nUruguay\n–First autochthonous transmission \nr\neported April 2023\nArgentina and southern Brazil\n–Transmission in new locations\nU.S traveler cases reported with \nt\nravel to this regionUruguayArgentinaParaguayBrazil\n14\nObservations on the outbreak of relevance to vaccine recommendations: \nExplosive nature of outbreaks\n<10,000 \nnotifications* by \nend of 2022\n>50, 000\nn\notifications* by \nweek 6, 2023\nSource: Ministry of Public Health and Social Welfare, Paraguay *Confirmed and probable cases and suspected arboviral infection15\nObservations on the outbreak of relevance to vaccine recommendations: \nImpact on young infants and older persons\nTorales M, et al. MMWR Weekly Rep 2023Number of hospitalizations (N=4,604) and case fatality rate among probable and \nconfirmed chikungunya cases by age group, October 1, 2022 –March 11, 2023\n16\nObservations on the outbreak of relevance to vaccine recommendations: \nImpact on young infants and older persons\nTorales M, et al. MMWR Weekly Rep 2023About three \nquarters of all \npatients who \ndied had \ncomorbiditiesNumber of hospitalizations (N=4,604) and case fatality rate among probable and \nconfirmed chikungunya cases by age group, October 1, 2022 –March 11, 2023\n17\nObservations on the outbreak of relevance to vaccine recommendations: \nImpact on neonates\n\nObservations on the outbreak of relevance to vaccine recommendations: \nImpact on health services\nPatient loadHealthcare \nstaff \nabsenteeism\nSummary of observations from outbreak in Paraguay\nOutbreak has been explosive and extensive\nGroups at risk for severe disease include infants, older adults, \na\nnd persons with comorbidities\nCase fatality rate highest among neonates \nImpact on health services from patient load and sick staff\n20\nAcknowledgements\nStaff of the M inistry \nof Public Health \nand Social Welfare, Paraguay\nAmy Beeson, CDC", "summary": "National Center for Emerging and Zoonotic Infectious Diseases UPDATE AND OBSERVATIONS ON A LARGE  CHIKUNGUNYA OUTBREAK IN PARAGUAY Susan Hills, MBBS, MTH CDC Lead , Chikungunya Vaccines Work Group Arboviral Diseases Branch Division of Vector -Borne Diseases Fort Collins, Colorado ACIP meeting, June 22, 2023 Chikungunya notifications* October 1, 2022 –June 3, 2023 167,239 cases Source: Ministry of Public Health and Social Welfare, Paraguay Epidemiologic weekNo. notifications *Confirmed and…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/04-Chikungunya-Hills-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 12}
{"title": "05 Chikungunya Hills 508", "content": "National Center for Emerging and Zoonotic Infectious Diseases\nWORK GROUP PLANS AND TIMELINES\nSusan Hills, MBBS, MTH\nCDC Lead , Chikungunya Vaccines Work Group\nArboviral Diseases Branch\nCenters for Disease Control and Prevention\nACIP meeting\nJune 22, 2023\nWork Group timeline (tentative)\nJun May Apr Mar Feb Jan Sept Jul Aug2024\nPresent EtRs (Today) Perceptions \nof chikungunya vaccine, Laboratory workers, Paraguay outbreakACIP vote on vaccine recommendations for adult travelers and laboratory workersOct Nov Dec Jan Feb Mar Apr2023\nFDA accepted BLA and \ngranted Priority ReviewPossible licensure\nConsideration of \nchikungunya vaccine use among residents \nof U.S. territories and states at risk for outbreaks\nLonger term Work Group plans and activities\nFuture presentations on topics relevant to consideration of vaccine use in \nU\n.S. territories and states with risk of transmission\nPossibly additional vaccine data in younger age groups and/or additional chi\nkungunya vaccines\n24\nThank you", "summary": "National Center for Emerging and Zoonotic Infectious Diseases WORK GROUP PLANS AND TIMELINES Susan Hills, MBBS, MTH CDC Lead , Chikungunya Vaccines Work Group Arboviral Diseases Branch Centers for Disease Control and Prevention ACIP meeting June 22, 2023 Work Group timeline (tentative) Jun May Apr Mar Feb Jan Sept Jul Aug2024 Present EtRs (Today) Perceptions  of chikungunya vaccine, Laboratory workers, Paraguay outbreakACIP vote on vaccine recommendations for adult travelers and laboratory…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/05-Chikungunya-Hills-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 4}
{"title": "01 RSV Mat Ped Long 508", "content": "1\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nMaternal/Pediatric Respiratory Syncytial Virus (RSV) \nWork Group\nSarah S. Long, MD\nChair, Maternal/Pediatric RSV Work Group \nACIP General Meeting\nJune 22, 2023\n\n2Work group members (External)\nACIP Members\nSarah Long (chair)\nPablo Sanchez\nOliver Brooks\nCamille Kotton\nEx Officio Members\nRachel Zhang (FDA -CBER)\nNicholas Geagan (FDA -CBER)\nJudy Beeler (FDA -CBER)\nYodit Belew (FDA -CDER)\nPrabha Viswanathan (FDA -CDER)\nSonnie Kim (NIH -NIAID)\nApril Killikelly (Public Health Agency of Canada)\nWinnie Siu (Public Health Agency of Canada)\nValerie Marshall (OIDP/OASH)\nJessica Lee (CMS/CMCS)\nTerry Dalle -Tezze (HRSA)\nLucia Lee (FDA -CBER)Consultants\nCody Meissner (Dartmouth Geisel School of Medicine)\nHelen Chu (University of Washington)\nNatasha Halasa (Vanderbilt University)\nDenise Jamieson (Emory University School of Medicine)\nDaniel Feikin (World Health Organization)\nCarol Baker (University of Texas Health Science Center)\nKevin Ault (Western Michigan University)Liaisons\nJames McAuley (IDSA)\nPatsy Stinchfield (NFID)\nBrenna L. Hughes (ACOG)\nNicole Chaisson (AAFP)\nSean O’Leary (AAP)\nJennifer Schuster (PIDS)\nMolly Howell (AIM)\nGRADE/ EtRconsultants\nDoug Campos -Outcalt\nRebecca Morgan\n3Work group members (CDC)\nLauren Roper\nAmber Winn\nChris Taylor\nTami Skoff\nAngie Campbell\nMichael Melgar\nAmanda Payne\nNicole Dowling\nNoelle MolinariClaire Midgley\nFiona Havers\nPragna Patel\nAndrea Sharma\nAmadea Britton\nRuth Link -Gelles\nDanielle Moulia\nMegan Wallace\nMonica GodfreyCDC ACIP Staff\nMelinda Wharton\nStephanie Thomas\nJessica MacNeilKaren Broder\nNaomi Tepper\nHannah Rosenblum\nHeidi Moline\nDerrell Powers\nRaigan Wheeler\nSally Ezra\nElizabeth GreeneCDC\nKatherine Fleming -Dutra (co -lead)\nJefferson Jones (co -lead)\nMeredith McMorrow\nMila Prill\nNatalie Thornburg\nAron Hall\nIsmael Ortega -Sanchez\nMelissa Coughlin\nJamison PikeA. Patricia Wodi\nNeil Murthy\nChristine Olson\nAnne Hause\nAndrew Leidner\nDavid Shay\n4▪Epidemiology and burden of RSV in infants\n▪Virology and immunology of RSV\n▪Safety and efficacy of nirsevimab\n▪Cost effectiveness analysis for nirsevimab –CDC model\n▪Cost effectiveness analysis for nirsevimab –Comparison to manufacturer model\n▪Evidence to Recommendations framework for nirsevimab\n▪Clinical considerations for nirsevimab\n▪Safety and Efficacy of RSV Bivalent PreF Maternal VaccinePrevious maternal/pediatric RSV ACIP presentations\n5Agenda: Thursday June 22, 2023\n▪Economic Analy sis of RSVpreFin \nPediatric Popul ations\n▪Evidence to Recommen dations \nFrame work f or Pfizer Maternal  RSVpreF\nVaccine\n▪Economics of combi ned use of Pfizer \nmaternal  RSVpreFvaccine and \nnirsevimab\n▪Clinical considerations for \nRSVpreFmaternal vaccine and \nnirsevimabDr. David Hutton (University of \nMichigan)\nDr. Kather ine Fleming-Dutra (CDC)\nDr. David Hutton (University of \nMichigan)\nDr. Jefferson Jones (CDC)\n6", "summary": "1 Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Maternal/Pediatric Respiratory Syncytial Virus (RSV)  Work Group Sarah S. Long, MD Chair,…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/01-RSV-Mat-Ped-Long-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 6}
{"title": "02 RSV Mat Ped Hutton 508", "content": "Economics of Pfizer maternal \nRSVpreF vaccine\nDavid W. Hutton, PhD, MS\nAssociate Professor, Health Management and Policy, School of Public Health\nAssociate Professor of Global Public Health, School of Public Health\nAssociate Professor, Industrial and Operations Engineering, College of Engineering\nUniversity of MichiganPresentation to the ACIP \nJune 22, 2023\n\nResearch team\nUniversity of Michigan\n•David Hutton, PhD\n•Lisa Prosser, PhD\n•Angela Rose, MPH\n•Kerra Mercon , MSCDC\n•Jefferson Jones, MD, MPH, \nFAAP\n•Mila Prill, MSPH\n•Meredith McMorrow, MD, \nMPH, FAAP\n•Jamison Pike, PhD\n•Katherine Fleming -Dutra, MD, \nFAAP\n•Ismael Ortega -Sanchez, PhD\n•Fiona Havers, MD\n•Betsy Gunnels, MSPH\n•Andrew Leidner , PhD\n2\nConflicts of interest statements\n–Authors have no known conflict of interests.\n3\nMethods: Study question\n•Determine the cost -effectiveness of RSVpreF by:\n•Evaluating the population impact in terms of \n•annual resource utilization \n•total cases\n•total costs \n•deaths\n•quality -adjusted life -years (QALYs)\n•Comparing the incremental cost -effectiveness ratio (ICER) of \nRSVpreF to natural history/no vaccine.\n•Running scenario analyses outcomes that explore key areas of \nuncertainty.\n•Perspective: Societal\n4\nMethods: Intervention(s)\n•Target population: US pregnant persons\n•Interventions:\n1.No vaccination (Natural history)\n2.RSVpreF against RSV illness\n•Timeframe: 1 year (1 RSV season)\n•Analytic horizon: infant’s lifetime\n•Discount rate: 3%\n5\nMethods: Decision tree model\n6Natural\nHistory\nRSVpreFInfection Hospitalization\nED\nNone of the aboveOutpatientAlive\nDeadInfection\nAdverse \nEventsPrematurity\nInjection site reaction\nNone of the aboveSerious adverse eventInfection Infection\nMethods: Epidemiology\nHospitalization\n7Base Case Range Source\nRespiratory syncytial virus (RSV) \nincidence, per 100,000 See Above See AboveCDC NVSN, \nDecember 2016 to September 2020\nProportion with LRTI\nAge 0 -5 months 1.0 0.5-1.0 Rainisch, 2020\nAge 6 -11 months 1.0 0.5-1.0 Rainisch, 2020\nCDC New Vaccine Surveillance Network (NVSN) hospitalization rates for children under 2 years of age from December 2016 to Sep tember 2020 - 1,000 2,000 3,000 4,000\n0246810121416182022Hospitalization \nrate  per 100,000 \nchildren\nAge in months\nMethods: Epidemiology\nED and Outpatient\n8Respiratory syncytial virus \n(RSV) incidence, per 100,000 Base \nCaseRange Source\nEmergency Department\nAge 0 -5 months 7,500 5,500 –7,500 Lively 2019 (base case and range), \nHall 2009 (range)\nAge 6 -11 months 5,800 5,700 –5,800 Lively 2019 (base case and range), \nHall 2009 (range)\nAge 12 -23 months 3,200 3,200 –5,300 Hall 2009 (base case and range), \nLively 2019 (range)\nProportion with LRTI\nAge 0 -5 months 0.65 0.25-1.0 Rainisch , 2020\nAge 6 -11 months 0.5 0.25-1.0 Rainisch , 2020\nOutpatient\nAge 0 -5 months21,60013,200 –\n21,600Lively 2019 (base case and range), \nHall 2009 (range)\nAge 6 -11 months24,60017,700 –\n24,600Lively 2019 (base case and range), \nHall 2009 (range)\nAge 12 -23 months18,4406,600 –29,620 Jackson 2021 (base case and \nrange), Hall 2009 (range)\nProportion with LRTI\nAge 0 -5 months 0.65 0.25-1.0 Rainisch , 2020\nAge 6 -11 months 0.3 0.1-1.0 Rainisch , 2020\nLRTI= Lower respiratory tract infection\nMethods: Epidemiology\nMortality\n9Base \nCaseRange Source\nRSV mortality per \nhospitalization\nAge 0 -5 months 0.04% 0.03-0.05% Doucette 2016\nAge 6 -11 months 0.04% 0.03-0.05% Doucette 2016\nAge 12 -23 months 0.3% 0.28% -\n0.34%Gupta 2016\nSeasonality\n100%5%10%15%20%25%30%\nApr May Jun JulAug Sep Oct Nov Dec Jan Feb MarFraction of Annual Infections\nSource: National Respiratory and Enteric Virus Surveillance System (NREVSS) (2015 -2019)\n110%20%40%60%80%100%\n0 3 6 9 12Efficacy\nMonth\nAgainst medically-attended RSV-associated LRTI\nAgainst hospitalizationMethods: RSVpreF efficacy\naverage 6 -month efficacy \n= trial efficacy \nZero efficacy\nSource: Kampmann et al 2023\nLRTI= Lower respiratory tract infection\n0%20%40%60%80%100%\n0 3 6 9 12Efficacy\nMonth\nAgainst medically-attended RSV-associated LRTI\nAgainst hospitalization\n12Methods: RSVpreF efficacy\nalternate scenario\naverage 6 -month efficacy \n= trial efficacy \nZero efficacy\nSource: Kampmann et al 2023\nLRTI= Lower respiratory tract infection\nMethods: Efficacy\n13Variable Base case \nvalueRange for \nsensitivity \nanalysisSource\nRSVpreF\nInitial efficacy (months 0 -5) \nagainst medically -attended \nRSV-associated LRTI 51.3% 29.4% -66.8%Kampmann\net al, 2023\nInitial efficacy (months 0 -5) \nagainst hospitalized RSV -\nassociated LRTI 56.8% 10.1% -80.7%Kampmann\net al, 2023\nEfficacy months 6 -12 0\nAssumed 0% efficacy against upper respiratory tract infections\nLRTI= Lower respiratory tract infection\nMethods: Provision of RSVpreF\n14•Base case:\n–Year round\n•Scenarios\n–During June -February (no vaccine given in \nMarch -May)\n–During May -February (no vaccine given in \nMarch -April)  \n–During April -February (no vaccine given in \nMarch) \n•Mother vaccinated \n–During 24 -36 weeks gestation, based on \ndistribution of Tdap vaccination by week in \nthat time period\n•Birth \n–Must be >2 weeks after vaccination for \nprotective efficacy to pass to infant, based on \nhistorical gestational age\n15 TDAP vaccination timing from internal CDC analysis of 2018 -2021 MarketScan data.Methods: Provision of RSVpreF\n16100 \nPregnant \npersons50 \nNot \nvaccinated\n50 \nVaccinated\n47 \nVaccinated\nin time3 \nNot \nvaccinated\nin timeMethods: Provision of RSVpreF\nUptake\nTiming\nTiming= >2 weeks prior to delivery\nMethods: Medical Costs\nVariable Value Range Source\nDisease -specific \nhospitalization costs \n(per hospitalization) \nAge 0 -11 months $11,487 4,804 -86,646\nBowser 2022Age 12 -23 months $11,469 4,804 -86,646\nDisease -specific ED \ncosts (per ED visit)$563 544 -581 Bowser 2022\nDisease -specific \noutpatient costs (per \noutpatient visit)$82 46 -118 Bowser 2022\n17•Bowser, 2022 is a systematic review using studies from 2014 -2021\n•Funded by Sanofi\n•All numbers updated to 2022 dollars using GDP Deflator\nMethods: Productivity costs\nVariable Value Range Source\nProductivity burden of \nRSV disease (caregiver \nlosses)\nDays of lost productivity\nOutpatient* 2.5 0-5Fragaszy, 2018; Petrie, \n2016; Van Wormer, 2017\nED* 2.5 0-5Fragaszy, 2018; Petrie, \n2016; Van Wormer, 2017\nHospitalization^ 7.4 0-14\nLifetime productivity for \nthose <1 year old (lost \nfrom death)1,795,936 1,346,951 -\n2,244,919Grosse, 2019\n18*Productivity for outpatient and ED based on adult influenza\n^Hospitalization productivity loss = length of hospitalization + 2 days\nMethods: Intervention cost\nVariable Value Range Source\nImmunization -related \ncosts\nRSVpreF , per dose $200 50 –300Assumption: Manufacturer \ncosts for adult vaccine\nRSVpreF administration $16.96 15 -22 Medicare: HCPCS 90460\n19Both assume no additional visits, but do include costs of administration\nMethods: Adverse event costs\nVariable Value Range Source\nRSVpreF Maternal \nAdverse Events\nRate of injection site \nreaction0.41 0.38 –0.44 Pfizer Phase 3 Trial\nProbability of healthcare \nvisit, given injection site \nreaction0.02 0.015 –0.025 Curran, 2020\nCost of outpatient visit $367.76 23.15 –1,758 (Deluca, 2023)\nRecipient time, physician \noffice for injection site \nreaction (hours)2 1 -3 Assumption \nHypothetical serious \nadverse event0.000001 0 -0.0002Base: Prosser, 2006\nHigh: 95% CI Phase 3 data for \nRSV adult vaccines\n20\n21Kampmann B, Madhi SA, Munjal I, Simões EA, Pahud BA, Llapur C, Baker J, Pérez Marc G, Radley D, Shittu E, Glanternik J. \nBivalent prefusion F vaccine in pregnancy to prevent RSV illness in infants. New England Journal of Medicine. 2023 Apr 5.Methods: Prematurity?\n1% Difference?\n\nMethods: Prematurity scenario\nVariable Value Range Source\nRSVpreF infant adverse \nevents\nHigher Rate of Prematurity 0% 0-2% Pfizer Phase 3 Trial\n22* All costs updated to 2022 using GDP DeflatorOutcomes, per \nprematurity\nLifetime cost of late \nprematurity\nMedical $ 23,241 $11,621 –\n$46,482 Waitzman , Jalali, Grosse, 2021\nProductivity $ 11,447 $5,724 –\n$22,894 Waitzman , Jalali, Grosse, 2021\nQALYs lost from late \nprematurity0.03 0 –1.2Werner, Hauspurg , Rouse, 2015\nPetrini et al, 2008, Hirvonen et al, 2014, Crump \net al, 2021, Darcy -Mahoney et al, 2016, Carroll \net al, 2009, Payakachat et al, 2014\nMethods: RSV \nhealth -related quality of life\n23LRTI quality -adjusted life DAYS lost Base Lower (Regnier) Upper (JIVE)\nOutpatient: Child 3.1 1.8 16.6\nOutpatient: Caregiver 1.5 0 9.1\nED: Child 4.9 2.9 16.6\nED: Caregiver 2.5 0 9.1\nHospitalized: Child 6.2 3.7 26.5\nHospitalized: Caregiver 2.4 0 13.6Measured in \nDays Lost\nMost \nLikely\nMethods: Uncertainty analyses\n•One-way sensitivity\n•Scenarios:\n–Prematurity\n–Cost \n–Month of administration\n–Upper respiratory tract infection effect \n–Efficacy waning\n24\nResults: Base case\n25•Base case:\n–Population of 1,000 births\n–50% uptake in the RSVpreF group\n–First RSV season\n–$200/dose\n–RSVpreF only impacts LRTI\nResults: Health outcomes\n26 Cohort:1,000 births, assuming 50% uptake in RSVpreF group\nURTI= upper respiratory tract infection; LRTI= lower respiratory tract infection - 50 100 150 200 250\nNatural\nHistoryRSVpreF Natural\nHistoryRSVpreF Natural\nHistoryRSVpreF\nOutpatient Emergency\nDepartmentInpatientNumber of Events in Cohort\nURTI LRTI\nResults: Events Averted\n27 Cohort:1,000 births, assuming 50% uptake in RSVpreF group12.9\n4.5\n2.1\n0.511.6\n1.4\n0.02.04.06.08.010.012.014.0\nOutpatient ED Inpatient ICU Inpatient Day ICU DayEvents Averted per 1000 births\nRSVPreF\nResults: Number Needed to \nVaccinate\n28 Cohort:1,000 births, assuming 50% uptake in RSVpreF group39 112 234 1,062 \n43 354 \n - 200 400 600 800 1,000 1,200\nOutpatient ED Inpatient ICU Inpatient Day ICU DayNumber needed to Vaccinate to avoid\nRSVPreF\nResults: Costs\n29\nBase costs of RSVpreF : $200/dose, both natural history and RSVPreF involve palivizumab for high -risk childrenCohort:1,000 births, assuming 50% uptake in RSVpreF group$0$100,000$200,000$300,000$400,000$500,000$600,000\nNatural History\nRSVPreF\nNatural History\nRSVPreF\nNatural History\nRSVPreF\nNatural History\nRSVPreF\nNatural History\nRSVPreF\nNatural History\nRSVPreF\nIntervention Outpatient ED Inpatient Deaths TotalTotal Costs in Cohort\nMedical Productivity\nResults: Cost per Event Averted\n30\nBase costs of RSVpreF : $200/dose$5,459 $15,722 $32,945 $149,751 \n$6,101 $49,917 \n $- $20,000 $40,000 $60,000 $80,000 $100,000 $120,000 $140,000 $160,000\nOutpatient ED Inpatient ICU Inpatient Day ICU DayCost per Event Averted\nRSVPreF\nResults: QALYs Lost\n31Adverse \nEventsOutpatient ED Inpatient Deaths Total Grand\nChild Caregiver Child Caregiver Child Caregiver Child Child Caregiver Total\nNatural \nHistory 1.95 0.98 0.90 0.45 0.22 0.09 0.15 3.22 1.51 4.73 \nRSVpreF 0.0001 1.85 0.93 0.84 0.42 0.19 0.07 0.12 3.00 1.42 4.42 \nCohort:1,000 births, assuming 50% uptake in RSVpreF group\nQALY= quality -adjusted life -year\nResults: Cost -Effectiveness\n32Base costs of RSVpreF : $200/dose\nQALY= quality -adjusted life -year; ICER= incremental cost -effectiveness ratioCohort:1,000 births, assuming 50% uptake in RSVpreF group, ICER is not affected by uptakeOverallCosts ($)QALYs \nlostICER ($/QALY)\nVs. NH\nNatural History 418,556 4.73 \nRSVpreF 489,038 4.40 214,087 \nSensitivity: Tornado RSVpreF\n33Base cost of RSVpreF : $200/dose\nMA= Medically -attended\nLRTI= Lower respiratory tract infection\nQALY= Quality adjusted life year$14 million$0 $100,000 $200,000 $300,000 $400,000 $500,000\nProbability of Prematurity\nDisease-specific inpatient costs (per inpatient case)  Age 0-5\nmonths\nRSV QALYS Lost\nRSVpreF vaccine cost/dose\nVaccination Efficacy, Hospitalized RSV LRTI through 180 days\nVaccination Efficacy, RSV MA-LRTI through 180 days\nProportion of RSV infections with an LRTI diagnosis Outpatient Age\n0-5 months\nRSV-related QALYs lost Outpatient Child\nRSV-related QALYs lost Outpatient Caregiver\nProportion of RSV infections with an LRTI diagnosis ED Visits Age\n0-5 monthsIncremental Cost -Effectiveness Ratio\nLow High\n $- $500,000 $1,000,000 $1,500,000 $2,000,000 $2,500,000 $3,000,000 $3,500,000 $4,000,000 $4,500,000 $5,000,000\n0.0% 0.5% 1.0% 1.5% 2.0%ICER\nExcess PrematurityScenario: Prematurity\n34Base Case\n $- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000\n$0 $50 $100 $150 $200 $250 $300ICER\nCost of RSVpreFSensitivity: Cost RSVpreF\n35Base Case\nResults: RSVpreF timing \nscenarios\n36•Scenarios\n–Base: vaccine given year -round\n–During April -February (no vaccine given in \nMarch) \n–During May -February (no vaccine given in \nMarch -April)  \n–During June -February (no vaccine given in \nMarch -May)\nResults: RSVpreF timing \nscenarios\n214,087 \n162,136 \n137,871 \n119,398 \n - 50,000 100,000 150,000 200,000 250,000\nBase Apr-Feb May-Feb Jun-FebICER ($/QALY)ICER: RSVpreF vs. Natural History\n37\n $- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000\n$0 $50 $100 $150 $200 $250 $300ICER\nTotal Cost of RSVpreFScenario: Upper Respiratory \nTract Infection Effect\n38RSVpreF is assumed to have 37.9% efficacy for upper respiratory tract infections based on overall respiratory tract \nefficacy from phase 3 trial ( Kampmann , 2023)\nICER= incremental cost effectiveness ratio; QALY= Quality adjusted life year$153,674/QALY\n39Methods: RSVpreF efficacy\n“flat efficacy” scenario\nOverallCosts ($)QALYs \nlostICER ($/QALY)\nNatural History 418,556 4.73 \nRSVpreF 486,812 4.38 191,749 \nSlightly lower costs with \nRSVpreF , slightly fewer \nQALYs lost, slightly lower \nICER0%20%40%60%80%100%\n0 3 6 9 12Efficacy\nMonth\nAgainst medically-attended RSV-associated LRTI\nAgainst hospitalization\nICER: Incremental cost -effectiveness ratio\nLRTI= Lower respiratory tract infection\nLimitations\n•Model Structure\n–No risk groups\n–No dynamic transmission. No impact of the vaccine \non transmission and indirect effects\n•Uncertain inputs\n–RSVpreF cost \n–QALYs lost \n–Upper respiratory tract infections\n–Prematurity\n40\nSummary\n•RSVpreF may improve RSV outcomes, but will \nalso increase costs\n•RSVpreF has the potential to be cost -effective\n•Results sensitive to:\n–Rate of prematurity \n–Cost per dose (Cost -Saving –350,000 $/QALY)\n–Efficacy (~150,000 -350,000 $/QALY)\n–QALYs lost (~50,000 -480,000 $/QALY)\n•Hospitalization, Outpatient, ED\n•Child, Parent\n–Month of Administration (~120,000 –215,000 $/QALY)\n41QALY: Quality -Adjusted Life -Year\nThank You\n•Please send comments to:\n•dwhutton@umich.edu\n42\nAppendix\n43\nMethods: Epidemiological model\nSeasonalityIncidence\n•Outpatient\n•ED\n•Hospitalizations\nNirsevimab\nWaning \nProtectionHealth Effects\n• Outpatient\n• ED\n• Hospitalizations\n• Deaths\nEconomic Effects\n• Intervention\n• Disease\n• Societal\n• QALYs\n• ICERInterventionsEpidemiology\nTiming\nCost Burden/\n•Outpatient\n•ED\n•HospitalizationsHealth Economics\nHealth Burden/\n•Outpatient\n•ED\n•Hospitalizations\n44\nMethods: Inputs\n•Incidence\n–Raw reported incidence may be \nunderreported because of imperfect PCR \nsensitivity, so we consider an additional \nscenario in sensitivity analysis:\n•based on CDC Unpublished re -analysis of raw \ndata from Zhang et al study which found \ndecreased RSV PCR sensitivity in light of paired \nserology testing (adjustment factor: 87.6%).\n45\nHealth -Related Quality -of-Life\n•Sources\n–Glaser (2022)\n•Estimate based on comparison of utility losses between premature \nchildren who had RSV vs. premature children without RSV and their \ncaregivers\n•Used as base case for hospitalization for children and their caregivers\n–Regnier (2013) \n•Estimate QALY losses for hospitalization, ED visits, and outpatient visits \nfor children with pertussis \n•Use relative QALYs between hospitalization, ED, and outpatient to \nestimate base losses for ED and outpatient in base case\n–JIVE RSV Utilities Survey (2021)\n•Estimates QALY losses for hospitalization and outpatient visits for child \nand caregiver\n•Estimates may be impacted by COVID -related concerns about \nrespiratory viruses\n•Inform upper bound of range\n46\n47 Timing of those who received vaccination during pregnancy\nRSVpreF is assumed to start earlier at week 24 (vs. week 27)00.020.040.060.080.10.120.140.160.18\n13579111315171921232527293133353739Fraction Vaccinated (given \nreceipt of vaccine)\nGestational Age\nReported Tdap Modeled RSVpreF vaccination timingMethods: Provision of RSVpreF\n480.0%5.0%10.0%15.0%20.0%25.0%30.0%35.0%40.0%45.0%\n0 10 20 30 40 50\nGestational Age (Week)\nSource: NCHS from 2019 and 2021Methods: Birth Timing\nValidation\n231\n66\n8225 \n65 \n13 \n050100150200250\nOutpatient Clinic\nVisitsED Visits HospitalizationsRates of Medically -Attended \nRSV (per 1000 births)\nRainisch et al, Vaccine, 2020 JIVE model\n49\nMethods: Maternal Adverse \nEvent Health Effects\nVariable Value Range Source\nAdult Quality -Adjusted Life -\nYears lost due to adverse events\nInjection Site Reaction 0 Assumed\nSerious Adverse Event 0.141 0.092 -0.199 Prosser, 2006\n50\nResults: Cost -Effectiveness\n51\nBase costs of RSVpreF : $200/doseCohort:1,000 births, assuming 50% uptake in RSVpreF group $410,000 $420,000 $430,000 $440,000 $450,000 $460,000 $470,000 $480,000 $490,000 $500,000\n (4.80)  (4.70)  (4.60)  (4.50)  (4.40)  (4.30)Costs \nQALYs (lost) from RSV \nNatural History RSVPreF\nResults: RSVpreF Administration \nJune -February\n52OverallCosts ($) QALYsICER \n($/QALY)\nVs. NH\nNatural \nHistory 418,556 4.73 \nRSVpreF 454,928 4.43 119,398", "summary": "Economics of Pfizer maternal  RSVpreF vaccine David W. Hutton, PhD, MS Associate Professor, Health Management and Policy, School of Public Health Associate Professor of Global Public Health, School of Public Health Associate Professor, Industrial and Operations Engineering, College of Engineering University of MichiganPresentation to the ACIP  June 22, 2023  Research team University of Michigan •David Hutton, PhD •Lisa Prosser, PhD •Angela Rose, MPH •Kerra Mercon , MSCDC •Jefferson Jones, MD,…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/02-RSV-Mat-Ped-Hutton-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 52}
{"title": "03 RSV Mat Ped Fleming Dutra 508", "content": "Centers for Disease Control and Prevention\nEvidence to Recommendations Framework: \nPfizer Maternal RSVpreF Vaccine\nKatherine Fleming -Dutra, MD\nCo-Lead, Respiratory Syncytial Virus Vaccines -Pediatric/Maternal Work Group \nCoronavirus and Other Respiratory Viruses Division\nNational Center for Immunization and Respiratory Diseases\nJune 22, 2023\n2Evidence to Recommendations (EtR) Framework\nPolicy Question\n▪Should vaccination with Pfizer RSVPreF vaccine (120µg antigen, 1 dose \nIM given 24 –36 weeks gestation) be recommended for pregnant people \nto prevent RSV disease in infants?\nRSVpreF is a bivalent recombinant stabilized prefusion F protein subunit vaccine\n3Evidence to Recommendations (EtR) Framework\nPICO Question\n▪Population Pregnant people 24 –36 weeks gestation\nIntervention Pfizer RSVPreF Vaccine\nComparison No vaccine\nOutcomes▪Medically attended RSV -associated lower respiratory tract infection in infants\n▪Hospitalization for RSV -associated lower respiratory tract infection in infants\n▪Intensive care unit (ICU) admission from RSV hospitalization in infants\n▪Mechanical ventilation from RSV hospitalization in infants\n▪RSV-associated death in infants\n▪All-cause hospitalization for lower respiratory tract infection in infants\n▪All-cause medically attended lower respiratory tract infection in infants\n▪Serious adverse events in pregnant people\n▪Reactogenicity (grade 3+) in pregnant people\n▪Serious adverse events in infants\n▪Preterm birth\n4Evidence to Recommendations (EtR) Framework\nEtR Domain Question(s)\nPublic Health Problem ▪Is the problem of public health importance?\nBenefits and Harms ▪How substantial are the desirable anticipated effects?\n▪How substantial are the undesirable anticipated effects?\n▪Do the desirable effects outweigh the undesirable effects?\nValues ▪Does the target population feel the desirable effects are large relative \nto the undesirable effects?\n▪Is there important variability in how patients value the outcome?\nAcceptability ▪Is the intervention acceptable to key stakeholders?\nFeasibility ▪Is the intervention feasible to implement?\nResource Use ▪Is the intervention a reasonable and efficient allocation of resources?\nEquity ▪What would be in the impact of the intervention on health equity?\nEtRDomain: Public Health Problem\nIs the problem of public health importance?\n6RSV is the leading cause of hospitalization in U.S. \ninfants1\n▪Most (68%) infants are infected in the first year of life \nand nearly all (97%) by age 2 years2\n▪2-3% of young infants will be hospitalized for RSV3,4,5\n▪RSV is a common cause of lower respiratory tract \ninfection in infants \n▪Highest RSV hospitalization rates occur in first months \nof life and risk declines with increasing age in early \nchildhood3,5\n▪79% of children hospitalized with RSV aged <2 years \nhad no underlying medical conditions3\n1Suh et al. JID 2022 . 2Glezen et al, Arch Dis Child, 1986 ; 3Hall et al, Pediatrics, 2013 ; 4Langley & Anderson, PIDJ, 2011 ; 5CDC NVSN data\nImage: Goncalves et al. Critical Care \nResearch and Practice 2012\n7Seasonality of RSV transmission —National Respiratory \nand Enteric Virus Surveillance System, NREVSS1, 2017 –\n2020\n0510152025\n27293133353739414345474951 135791113151719212325\nJul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun% PCR results RSV -positive\nEpidemiologic week\nAbbreviation : PCR = polymerase chain reaction; RSV = respiratory syncytial virus. 1. https://www.cdc.gov/mmwr/volumes/72/wr/mm7214a1.htm\n* 3-week centered moving averages of percentage of RSV -positive PCR results nationwide. The black dotted line represents the thr eshold for a seasonal epidemic (3% RSV -positive laboratory PCR results). \n8Changes in seasonality of RSV transmission following \nSARS -CoV2 introduction —NREVSS1, 2017 –2023\n0510152025\n27293133353739414345474951 135791113151719212325\nJul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun% PCR results RSV -positive\nEpidemiologic week2017 –18 2018 –19 2019 –20 2020 –21 2021 –22 2022 –23\nAbbreviation : PCR = polymerase chain reaction; RSV = respiratory syncytial virus. 1. https://www.cdc.gov/mmwr/volumes/72/wr/mm7214a1.htm\n* 3-week centered moving averages of percentage of RSV -positive PCR results nationwide. The black dotted line represents the thr eshold for a seasonal epidemic (3% RSV -positive laboratory PCR results). \n9Public Health Problem -Work Group Interpretation\n▪Is RSV among infants of public health importance? \nNoProbably \nNoProbably \nYesYes VariesDon’t \nknow\nEtRDomain: Benefits and Harms\nHow substantial are the desirable anticipated effects?\nHow substantial are the undesirable anticipated effects?\nDo the desirable effects outweigh the undesirable effects?\n11GRADE Outcomes, Importance, and Data Sources: \nPfizer maternal RSVpreF vaccine\nOutcome Importance1 Data sources\nBenefits\nMedically attended RSV -associated lower respiratory tract infection in infants Critical Phase 3 RCT\nHospitalization for RSV -associated lower respiratory tract infection in infants Critical Phase 3 RCT\nICU admission from RSV hospitalization in infants Important No data\nMechanical ventilation from RSV hospitalization in infants Important No data\nRSV-associated death in infants Important Phase 3 and phase 2b2RCT\nAll-cause medically attended lower respiratory tract infection in infants Important Phase 3 RCT\nAll-cause hospitalization for lower respiratory tract infection in infants Important No data\nHarms\nSerious adverse events in pregnant people Critical Phase 3 and phase 2b2RCT\nReactogenicity (grade 3+) in pregnant people Important Phase 3 and phase 2b2RCT\nSerious adverse events in infants Critical Phase 3 and phase 2b2RCT\nPreterm birth (<37 weeks) Critical Phase 3 and phase 2b2RCT\nRCT = Randomized -controlled trial\n1 Three options: Critical; Important but not critical; Not important for decision making\n2 Among phase 2b trial participants, only those who received the vaccine formulation of the phase 3 trial were included\n12Efficacy estimates and concerns in certainty of \nassessment, benefits : Pfizer maternal RSVpreF vaccine\nOutcome Importance1 Data sources Manufacturer \ncalculated vaccine \nefficacy (97.58% or \n99.17% CI)2Concerns in certainty \nassessment\nBenefits\nMedically attended RSV -associated lower respiratory tract infection in \ninfants (0 –180 days)Critical Phase 3 RCT 51.3% (29.4, 66.8) None\nHospitalization for RSV -associated lower respiratory tract infection in \ninfants (0 –180 days)Critical Phase 3 RCT 56.8% (10.1, 80.7) Imprecision (serious)3\nICU admission from RSV hospitalization in infants Important No data\nMechanical ventilation from RSV hospitalization in infants Important No data\nRSV-associated death in infants Important Phase 3 and phase 2b4\nRCT1 RSV -associated death occurred in the placebo arm of the \nphase 3 trial that was recorded at day 120 after birth. No \nRSV-associated deaths were recorded in the phase 2b trial.\nAll-cause medically attended lower respiratory tract infection in \ninfants (0 –180 days)Important Phase 3 RCT 2.5% ( -17.9, 19.4) Imprecision (serious)3\nAll-cause hospitalization for lower respiratory tract infection in infants Important No data\nRCT = Randomized -controlled trial\n1 Three options: Critical; Important but not critical; Not important for decision making\n2 Vaccine efficacy was calculated as 1 –(P/[1 –P]), where P is the number of cases in the RSVpreF group divided by the total number of cases. The confidence interval was \nadjusted using the Bonferroni procedure and accounting for the primary endpoints results. 97.58% confidence interval used for medically attended RSV -associated lower \nrespiratory tract infection in infants, 99.17% confidence interval used for other endpoints. \n3 Serious concern for imprecision due to the width of the confidence interval containing estimates for which different policy decisions might be considered\n4  Among phase 2b trial participants, only those who received the vaccine formulation of the phase 3 trial were included\n13Efficacy estimates and concerns in certainty of \nassessment, harms : Pfizer maternal RSVpreF vaccine\nOutcome Importance1Data sources Relative Risk2 (95% \nconfidence interval)Concerns in certainty \nassessment\nHarms\nSerious adverse events in pregnant people Critical Phase 3 and \nphase 2b2RCT1.06 (0.95, 1.17) Imprecision (serious)3\nReactogenicity (grade 3+) in pregnant people Important Phase 3 and \nphase 2b2RCT0.97 (0.72, 1.31) Indirectness (serious)4\nSerious adverse events in infants Critical Phase 3 and \nphase 2b2RCT1.01 (0.91, 1.11) Imprecision (serious)3\nPreterm birth (<37 weeks) Critical Phase 3 and \nphase 2b2RCT1.20 (0.99, 1.46) Imprecision (very serious)5\nRCT = Randomized -controlled trial\n1 Three options: Critical; Important but not critical; Not important for decision making\n2 Pooled relative risk estimates were independently calculated using counts of events and participants in the phase 3 trial i nterim analysis, and phase 2b trial among those \nwho received the phase 3 vaccine formulation\n3 Serious concern for imprecision due to the width of the confidence interval containing estimates for which different policy decisions might be considered\n4 Serious concern for indirectness as these data only includes systemic reactions \n5 Very serious concern for imprecision due to the width of the confidence interval containing estimates for which different p olicy decisions might be considered and not \nmeeting optimal information size requirements\n14Summary of GRADE: Pfizer maternal RSVpreF vaccine\nOutcome Importance Design (# of \nstudies)Findings Evidence Type\nBenefits\nMedically attended RSV -associated lower respiratory \ninfection in infants Critical RCT (1) Pfizer RSVPreF maternal vaccine is effective in preventing medically \nattended RSV -associated lower respiratory infection in infants High\nHospitalization for RSV -associated lower respiratory \ntract infection in infants Critical RCT (1) Pfizer RSVPreF maternal vaccine may be effective in preventing \nhospitalization for RSV -associated lower respiratory tract infection in \ninfants Moderate\nICU admission from RSV hospitalization in infants Important No data Not evaluated\nMechanical ventilation from RSV hospitalization in \ninfants Important No data Not evaluated\nRSV-associated death in infants Important RCT (2) 1 event observed in a placebo recipient among both trials Not evaluated\nAll-cause medically attended lower respiratory tract \ninfection in infants Important RCT (1) Pfizer RSVPreF maternal vaccine is not effective in preventing all -cause \nmedically attended lower respiratory tract infection in infants Moderate\nAll-cause hospitalization for lower respiratory tract \ninfection in infants Important No data Not evaluated\nHarms\nSerious adverse events in pregnant people Critical RCT (2) SAEs in pregnant people were balanced between vaccine and placebo \ngroupsModerate\nReactogenicity (grade 3+) in pregnant people Important RCT (2) Reactogenicity in pregnant people was balanced between vaccine and \nplacebo groupsModerate\nSerious adverse events in infants Critical RCT (2) SAEs in infants were balanced between vaccine and placebo groups Moderate\nPreterm birth (<37 weeks) Critical RCT (2) Preterm births were unbalanced between vaccine and placebo groups Low\n15Summary of GRADE: Pfizer maternal RSVpreF vaccine\n15Overall \nevidence type: \nLow\n\n16Outcome: Preterm births (n=2 studies), Pfizer maternal \nRSVpreF vaccine\n16Publication Definition Events/Vaccine\n(n/N)Events/Placebo\n(n/N)Relative Risk (95% CI)\nPhase 3<34 weeks 21/3568 12/3558 1.75 (0.86, 3.54)\n<37 weeks 201*/3568 169/3558 1.19 (0.97, 1.45)\nPhase 2b<34 weeks 0/115 1/117 0.34 (0.01, 8.24)\n<37 weeks 6/115 3/117 2.03 (0.52, 7.94)\n*When reported as an adverse event of special interest, 202 preterm births occurred in the vaccine arm; the relative risk is minimally changed at 1.19 (0.98, 1.45) when using this count\n17Outcome: Preterm births (n=2 studies), Pfizer maternal \nRSVpreF vaccine\n▪Measures of effect\n–Relative risk: 1.20 (0.99, 1.46)\n–Absolute risk*:  9 more per 1,000 (from 0 fewer to 22 more)\n▪Concerns in certainty assessment:\n–Very se rious concern for imprecision due to the width of the \nconfidence interval containing estimates for which different policy \ndecisions might be considered and not meeting optimal information \nsize requirements\n▪Evidence type: Low\n*Absolute risk was calculated using the observed outcomes in the placebo arm during the available clinical trial follow -up. Abso lute risk estimates should be \ninterpreted in this context.\n18Preterm birth rates in maternal RSV vaccine clinical \ntrials: GSK\n▪Trial of a similar GSK maternal RSV vaccine (stabilized prefusion F protein vaccine \nwithout an adjuvant) was halted due to an imbalance of preterm births\n▪Imbalance of neonatal deaths was a consequence of preterm birth imbalance\n▪Imbalance in preterm births was seen in low and middle -income countries (RR: 1.57, \n95% CI: 1.17, 2.10) but not high -income countries (RR: 1.04, 95% CI: 0.68, 1.58)\n▪Imbalance was observed from April -December 2021, but not consistently after \nDecember 2021  \n▪Reason for the imbalance remains unclear\nStudy vaccine given at 240/7to 340/7weeks gestation\nVaccines and Related Biological Products Advisory Committee February 28 -March 1, 2023 Meeting Briefing Document -Sponsor GSK ( fda.gov)Outcome Vaccine group, n (%) \nN=3,496Placebo group, n (%)\nN=1,739Relative Risk\n(95% CI)\nPreterm birth <37 weeks 238 (6.81%) 86 (4.95) 1.38 (1.08, 1.75)\nNeonatal death 13 (0.37%) 3 (0.17%) 2.16 (0.62, 7.55)\n19Preterm birth rates in maternal RSV vaccine clinical \ntrials: Novavax\n▪Phase 3 clinical trial in 4,636 women randomized 2:1, vaccine to placebo\n▪Vaccine formulation: 120μg of recombinant RSV F protein nanoparticle vaccine \nadsorbed to 0.4mg of aluminum (Novavax vaccine was not stabilized in the \nprefusion form)\n▪Maternal vaccine did not reach primary efficacy endpoints and thus did not move \nforward, but there were no safety concerns (preterm births or other) in this trial \nPreterm Birth Definition Preterm Birth in Vaccine group, \nn (%)\nN=2,986Preterm Birth in Placebo, \nn (%)\nN=1,554\n<37 weeks among infants* 175 (5.9%) 96 (6.2%)\n*Study vaccine given at ≥28 through 36 weeks and 0 days gestation. Data from Table 1 among infants for whom the protocol -mandated dating ultrasonography result was \navailable for calculating gestational age.\n1. Madhi SA, Polack FP , Piedra PA, et al. Respiratory syncytial virus vaccination during pregnancy and effects in infants. N Engl J Med 2020;383:426 -39. DOI: \n10.1056/NEJMoa1908380\n20Preterm birth and low birth weight outcomes in \nmaternal RSV vaccine clinical trials: Pfizer RSVpreF \nvaccine phase 3 trial data\n*Confidence intervals not reported for these estimates. \nVaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Presentation -Review of Efficacy and Safety of Respiratory Syncytial Virus Vaccine (ABRYSVO) \n(fda.gov)RSVpreF vaccine group\nN=3,568Placebo group\nN=3,558\nPreterm birth (<37 weeks) 5.7% (95% CI: 4.9%, 6.5%) 4.7% (95% CI: 4.1%, 5.5%)\nLate preterm birth (≥34 to \n<37 weeks)5.0%* 4.4%*\nLow birth weight ( ≤2500g) 5.1% (95% CI: 4.4%, 5.8%) 4.4% (95% CI: 3.7%, 5.0%) \n21Infant deaths in maternal RSV vaccine clinical trials: \nPfizer RSVpreF vaccine phase 3 trial data\n▪Infant deaths (all -cause) through 24 months of age: 5 (0.1%) in the \nRSVpreF group vs 12 (0.3%) in placebo group\n▪Among infant deaths in the RSVpreF group\n–4 of 5 deaths were considered unrelated to the investigational product \nby FDA\n–1 death was in an infant with extreme prematurity (27 weeks) and \nprematurity -related complications, and FDA was unable to exclude \npossibility of relationship to investigational product\nVaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Presentation -Review of Efficacy and Safety of Respiratory Syncytial Virus Vaccine (ABRYSVO) \n(fda.gov)\n22\nTime from Vaccination to Birth Among Preterm and \nTerm Births, Infant Participants, Safety Population: \nPfizer RSVpreF vaccine phase 3 trial data\n▪Median gestational age at vaccination in trial was 31 weeks\nVaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Presentation -Review of Efficacy and Safety of Respiratory Syncytial Virus Vaccine (ABRYSVO) \n(fda.gov)\n23Subgroup analysis of gestational age at birth among \nlive births by country income level : Pfizer RSVpreF\nvaccine phase 3 trial data\n▪In high -income countries, preterm birth rate was 5.1% (126/2494) in \nRSVpreF recipients vs 5.1% (126/2484) placebo recipients\n▪Imbalance was most prominent in upper middle income countries: 7.5% \n(72/964) in RSVpreF recipients vs. 4.1% (39/961) in placebo recipients\nVaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Briefing Document -FDA\n24\nSubgroup analysis of gestational age at birth among \nlive births, South Africa and US: Pfizer RSVpreF vaccine \nphase 3 trial data\nTrial was conducted in 18 countries. \nVaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Briefing Document -FDA▪In South Africa, preterm birth rate was 8.3% (39/469) in RSVpreF recipients \nvs 4.0% (19/471) placebo recipients\n▪In US, preterm birth rate was 5.7% (94/1654) in RSVpreF recipients vs. 5.3%\n(87/1644) in placebo recipients\n25VRBPAC discussion regarding preterm births: Pfizer \nRSVpreF vaccine \n▪An imbalance was seen in preterm births in both phase 2b and phase 3 \ntrials, but the imbalance was not statistically significant\n▪Preterm birth rate in trials was lower than background incidence rate of \npreterm birth (~10% in US), but the trial had multiple exclusion criteria \nselecting for a population at lower risk of preterm birth\n▪Trial was underpowered to detect a 20% relative increase in preterm birth\n181st Meeting of the Vaccines and Related Biological Products Advisory Committee –YouTube\nPreterm Birth | Maternal and Infant Health | Reproductive Health | CDC\n26VRBPAC discussion regarding preterm births: Pfizer \nRSVpreF vaccine (cont.)\n▪Imbalance was still present but less pronounced when comparing \nprevalence of low birth weight\n▪Most preterm births were late preterm ( ≥34 to <37 weeks)\n▪Most preterm births were >30 days after vaccination\n▪Preterm birth imbalance was most prominent in a single country, South \nAfrica\n▪VRBPAC voted 14 -0 that the data supported effectiveness of Pfizer \nmaternal RSVpreF and voted 10 -4 that data supported safety\n181st Meeting of the Vaccines and Related Biological Products Advisory Committee -YouTube\n27Other considerations: Inflammatory neurologic events \nPfizer RSVPreF Vaccine\n▪Same Pfizer RSV vaccine, formulation and dose approved for use in older adults\n▪Within the main phase 3 trial for this product among adults ages ≥ 60 years (RENOIR) \na potential neurologic safety signal was identified\n▪A total of 3 cases of potential inflammatory neurologic events were recorded among \n20,255 investigational vaccine recipients across all clinical trials. No cases were \nobserved among placebo recipients.\nhttps://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2023 -06-21-23/06 -RSV-Adults -Melgar -508.pdf)\n28Other considerations: Inflammatory neurologic events \nPfizer RSVPreF Vaccine (cont.)\n▪No Guillain -Barré Syndrome (GBS) or other demyelinating events were \nreported in the phase 2b or 3 trials among pregnant people1\n▪Background rate of GBS in pregnant people is much lower than among \nolder adults2,3\n–Incidence rate of GBS in pregnant people in the Vaccine Safety Datalink during \n2004 -2015: 2.8 (95% CI 0.5 –9.3) per million person -years (based on 2 cases)2\n1.Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Briefing Document -FDA\n2.Myers TR, McCarthy NL, Panagiotakopoulos L, Omer SB. Estimation of the Incidence of Guillain -Barré Syndrome During Pregnancy in the United States. Open Forum \nInfect Dis. 2019 Mar 15;6(3):ofz071. doi: 10.1093/ ofid/ofz071. \n3.Sejvar JJ, Baughman AL, Wise M, Morgan O. Population Incidence of Guillain -Barré Syndrome: A Systematic Review and Meta -Analysis. Neuroepidemiology \n2011;36:123 –133 \n29Benefits and Harms Pfizer Maternal RSVPreF Vaccine\n▪How substantial are the desirable anticipated effects?\n–How substantial are the anticipated effects for:\n•Medically attended RSV -associated lower respiratory infection in infants \n•Hospitalization for RSV -associated lower respiratory tract infection in \ninfants \n•ICU admission from RSV hospitalization in infants \n•Mechanical ventilation from RSV hospitalization in infants \n•RSV-associated death in infants \n•All-cause hospitalization for lower respiratory tract infection in infants \n•All-cause medically attended lower respiratory tract infection in infants \nMinimal Small Moderate Large Varies Don’t know\n30Benefits and Harms Pfizer Maternal RSVPreF Vaccine\n▪How substantial are the undesirable anticipated effects?\n–How substantial are the anticipated effects for:\n•Serious adverse events in pregnant women \n•Reactogenicity (3+ or higher) in pregnant women \n•Serious adverse events in infants \n•Preterm birth \nMinimal Small Moderate Large Varies Don’t know\nMinority Opinion\n31Benefits and Harms Pfizer Maternal RSVPreF Vaccine\n▪Do the desirable effects outweigh the undesirable effects?\n–What is the balance between the desirable effects relative to the \nundesirable effects?\nFavors intervention (Pfizer Maternal RSVPreF \nVaccine)\nFavors comparison (No intervention)\nFavors both\nFavors neither\nUnclear\nEtRDomain: Values\nCriterion 1: Does the target population feel that the desirable effects are \nlarge relative to undesirable effects? \nCriterion 2: Is there important uncertainty about, or variability in, how \nmuch people value the main outcomes?\n33University of Iowa, RAND, and CDC Values Survey, \nDecember 21, 2022 -January 2, 2023\n▪523 participants\n–Pregnancy status:*\n•58.1% currently pregnant\n•44.9% given birth in the last 12 months\n–Race and Ethnicity:*\n•66.0% Non -Hispanic White \n•16.5% Non -Hispanic Black\n•9.8% Hispanic\n•7.7% Other Race/Ethnicity\n▪68% of respondents had knowledge of RSV prior to taking survey\n*Participants were able to select all applicable answer choices.\nCDC and University of Iowa/RAND survey, unpublished\n3461% of respondents said they ‘definitely’ or ‘probably’ \nwould get an RSV vaccine while pregnant\nCDC and University of Iowa/RAND survey, unpublished\n35Among those who did not respond that they “definitely would” get an RSV \nvaccine while pregnant, safety concerns, lack of RSV knowledge, and concerns \nabout vaccination causing or intensifying RSV infection were the top reasons \nfor not wanting an RSV vaccine during pregnancy\nCDC and University of Iowa/RAND survey, unpublished\n3622% of respondents did not want any vaccines or were unsure about how \nmany vaccines they would be willing to get in the same healthcare visit \nduring pregnancy\nPrefer not to say\n0%Unsure  \n10%No vaccines\n12%One vaccine\n17%Two vaccines\n32%\nThree vaccines\n9%Four vaccines\n20%\n0%10%20%30%40%50%60%70%80%90%100%% of respondents (n=523)\nCDC and University of Iowa/RAND survey, unpublished\n37\nTdap vaccine coverage among pregnant women (n=838), \nby race and ethnicity —Internet Panel Survey, United \nStates, April 2020 –April 2022 \nFlu, Tdap, and COVID -19 Vaccination Coverage Among Pregnant Women –United States, April 2022 | FluVaxView | Seasonal Influenza (Flu) | CDC\n38Values\n▪Criterion 1: Do pregnant people feel that the desirable effects are large \nrelative to undesirable effects?\nNo Probably No Probably Yes Yes Varies Don’t know\n39Values\n▪Criterion 2: Is there important uncertainty about, or variability in, how \nmuch pregnant people value the main outcomes?\nImportant uncertainty or variability\nProbably important uncertainty or variability\nProbably not important uncertainty or variability\nNo important uncertainty or variability\nNo known undesirable outcomes\nMinority Opinion\nEtRDomain: Acceptability\nIs the intervention acceptable to key stakeholders?\n41Maternity healthcare professionals survey —England, \n2019\n▪Obstetrician and midwife support of RSV vaccine, if it was routinely \nrecommended:\n–47% definitely\n–34% likely\n–14% not sure\n–4% unlikely\n–0.5% very unlikely\nWilcox, CR; Calvert, A; Metz, J et al. Attitudes of Pregnant Women and Healthcare Professionals Toward Clinical Trials and Routine Implementation of Antenatal Vacci nation \nAgainst Respiratory Syncytial Virus: A Multicenter Questionnaire Study. The Pediatric Infectious Disease Journal 38(9):p 944 -951, September 2019. | DOI: \n10.1097/INF.0000000000002384\n42Acceptability\n▪Is RSV prevention with Pfizer maternal RSVPreF vaccine acceptable to \nkey stakeholders?\nNo Probably No Probably Yes Yes Varies Don’t know\nEtRDomain: Feasibility\nIs the intervention feasible to implement?\n44Storage and handling requirements\n▪Supplied as single 0.5 mL dose, or as a 5 -pack or 10 -pack of single -dose \nkits \n▪Reconstitution required: single dose vial of lyophilized powder, \nreconstitution supplies included in kit \n▪Product should be refrigerated (2 –8°C) in original container, protected \nfrom light \n▪After reconstitution, the product should be administered within 4 \nhours, otherwise discarded\nShowLabeling.aspx (pfizer.com) and Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Presentation -Bivalent RSV Prefusion F \nVaccine for Maternal Immunization to Protect Infants (fda.gov)\n45Timing of RSVPreF vaccination during pregnancy\n▪Trial dosing was between 24 through 36 weeks gestation\n▪Median gestational age at vaccination in phase 3 trial was 31 weeks1\n▪Administration of maternal RSVPreF vaccine during regularly scheduled \nprenatal visits and bundling with recommended screening tests and \nother recommended vaccinations could also improve feasibility\n–Tdap recommended every pregnancy, preferably during the early part \nof gestational weeks 27 through 362\n–Glucose challenge test recommended at 26 -28 weeks gestation3\n1. FDA. Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Presentation -Review of Efficacy and Safet y of Respiratory Syncytial \nVirus Vaccine (ABRYSVO) (fda.gov)\n2. CDC, https://www.cdc.gov/vaccines/vpd/dtap -tdap -td/hcp/recommendations.html\n3. US HHS OASH, https://www.womenshealth.gov/pregnancy/youre -pregnant -now -what/prenatal -care -and-\ntests#:~:text=Typically%2C%20routine%20checkups%20occur%3A,for%20weeks%2036%20to%20birth\n46Efficacy against medically attended RSV -associated \nlower respiratory tract disease by gestational age at \nvaccination \nSubgroup Gestational Age at \nVaccinationRSVpreF \n(N= 3495) \nnRSVpreF \n(N= 3495) \n# cases (%)Placebo \n(N=3480)\nnPlacebo \n(N=3480) \n# cases (%)VE (%) (95% CI)\nInterim analysis at 180 days -- -- -- -- --\n≥24 weeks to <28 weeks 890 22 (2.5) 866 27 (3.1) 20.7 ( -44.6, 57.0)\n≥28 weeks to <32 weeks 1030 11 (1.1) 1070 35 (3.3) 67.4 (34.2, 85.0)\n≥32 weeks to ≤36 weeks 1572 24 (1.5) 1539 55 (3.6) 57.3 (29.8, 74.7)\nVaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Presentation -Review of Efficacy and Safety of Respiratory Syncytial Virus Vaccine (ABRYSVO) \n(fda.gov)Source: adapted from Pfizer 1008 CSR\nAbbreviations: RSV= respiratory syncytial virus; VE= vaccine efficacy; CI= confidence interval\nNote: this subgroup analysis did not appear in the FDA Briefing Document \n47Potential considerations for timing of RSV vaccine \ndosing during the year\n▪RSV vaccine dosing could be implemented for pregnant people as a \nseasonal campaign or year -round \n▪Year -round dosing\n–Simplify implementation and potentially increase vaccine uptake\n–Protect infants in the event of atypical RSV seasonality\n–Is less cost -effective\n▪Limited benefit for doses given during March -May changes benefit/risk \ncalculation\n48Potential considerations for timing of RSV vaccine \ndosing during the year (cont.)\n▪Some U.S. jurisdictions have different or less predictable RSV \nseasonality, and recommendations for RSV vaccine dosing in those \njurisdictions would need to account for that\n–Tropical climates: parts of Florida, Puerto Rico, U.S. Virgin Islands, \nHawaii, Guam, and U.S. -affiliated Pacific Islands\n–Alaska: RSV seasonality is less predictable, and the duration of RSV \nactivity is often longer than the national average\n49Simultaneous administration of RSV vaccines in \npregnant people\n▪Pregnant people may potentially be eligible to receive RSV, Tdap, \nCOVID -19, and influenza vaccines at same visit\n▪No available data on simultaneous administration of RSVpreF vaccine in \npregnant people and limited data in non -pregnant people\n▪According to CDC’s immunization general best practices, age -\nappropriate vaccinations can be administered simultaneously, with two \nspecific exceptions1,2\n1. In persons with anatomic or functional asplenia and/or HIV infection, quadrivalent meningococcal conjugate vaccine (MCV4) -D (MenACWY -D, Menactra ) and \npneumococcal conjugate vaccine (PCV)13 (PCV13, Prevnar 13) should not be administered simultaneously. In patients recommended toreceive both PCV13 and PPSV23, \nthe 2 vaccines should not be administered simultaneously. ACIP Timing and Spacing Guidelines for Immunization | CDC\n50Available data on simultaneous administration with \nPfizer RSVpreF vaccine\n▪Pfizer Phase 2b study in healthy non-pregnant women ages 18 -49 on \ncoadministration of Tdap and Pfizer RSVpreF1\n–Coadministration of Tdap and Pfizer RSVpreF led to decreased immune response to \npertussis components (i.e. non -inferiority criteria were not met)\n▪Phase 3 study in non-pregnant adults ages ≥65 years on coadministration of \nRSVpreF and adjuvanted seasonal quadrivalent influenza vaccine2\n–Non-inferiority criteria were met for antibody titers against all 4 influenza strains, \nas well as RSV -A and RSV -B\n▪No safety concerns in either trial\n▪Neither trial evaluated efficacy (not powered)\n1. Peterson et. al. Safety and Immunogenicity of a Respiratory Syncytial Virus Prefusion F Vaccine When Coadministered With a Te tanus, Diphtheria, and Acellular Pertussis \nVaccine, The Journal of Infectious Diseases, Volume 225, Issue 12, 15 June 2022, Pages 2077 –2086 ,https://doi.org/10.1093/infdis/jiab505\n2. Safety and Immunogenicity of RSVpreF Coadministered With SIIV in Adults ≥65 Years of Age -Full Text View -ClinicalTrials.gov\n51Pertussis immunogenicity and co -administration in \nadolescents and adults\n▪There is no accepted correlate of protection for pertussis vaccination\n–In the absence of a correlate of protection, non -inferiority is used to assess \nimmunogenicity of co -administration\n–Clinical significance of failing to meet non -inferiority for pertussis is unclear \n▪Some studies in adolescents and adults looking at Tdap coadministration \nwith other vaccines, including meningococcal and influenza vaccines, failed \nto demonstrate non -inferiority against at least one pertussis antibody, but \ncoadministration is still recommended\n▪Unclear how this might impact protection against pertussis from maternal \nTdap when co -administered with RSVpreF\nLiang JL, Tiwari T, Moro P , et al. Prevention of Pertussis, Tetanus, and Diphtheria with Vaccines in the United States: Recom men dations of the Advisory Committee on \nImmunization Practices (ACIP). MMWR Recomm Rep 2018;67(No. RR -2):1–44. DOI: http://dx.doi.org/10.15585/mmwr.rr6702a1 external icon\n52\nPlace of Flu, Tdap, COVID -19 Vaccination among \nPregnant Women, United States, Internet Panel \nSurvey, April 2022\nFlu, Tdap, and COVID -19 Vaccination Coverage Among Pregnant Women –United States, April 2022 | FluVaxView | Seasonal Influenza (Flu) | CDC“Other place” includes other medical or non -medical place, including school or special site for COVID -19 vaccination\n53Availability of vaccines to pregnant people by practice \ntype\n▪Survey of health care providers conducted in Fall 2022\nProvider type (%)\nTotal \n(n=1,538)Family \nPractitioner/ \nInternist Pediatrician OB/GYN NP/PA\nTdap 72% 73% 79% 74% 58%\nCOVID -19 53% 56% 66% 40% 49%\nInfluenza 81% 85% 83% 74% 67%\nOb/Gyn =Obstetrician -Gynecologist; NP/PA: Nurse Practitioner or Physician’s Assistant \nUnpublished data, Fall 2022 DocStylesProportion of practices that offer or administer vaccinations on site to pregnant patients\n54Feasibility\n▪Is Pfizer Maternal RSVPreF vaccine feasible to implement among \npregnant people at 24-36 weeks gestation?\nNo Probably No Probably Yes Yes Varies Don’t know\nMinority Opinion\nEtRDomain: Resource Use\nIs the intervention a reasonable and efficient allocation of resources?\n56Summary of Economic Analysis of RSVPreF in Pediatric \nPopulations\n▪RSVPreF has the potential to be cost -effective\n–Base case ICER: $214,087/QALY \n▪Results sensitive to:\n–Rate of prematurity \n–Cost per dose\n–Efficacy\n–QALYs lost\n–Timing of vaccination: year -round vs seasonal (e.g., June -February)\nICER: Incremental cost -effectiveness ratio; QALY: Quality -adjusted life year\n57Resource Use\n▪Is Pfizer Maternal RSVPreF vaccine use among pregnant people at 24 –\n36 weeks gestation a reasonable and efficient allocation of resources?\nNo Probably No Probably Yes Yes Varies Don’t know\nEtRDomain: Equity\nWhat would be in the impact of the intervention on health equity?\n59Population -based hospitalization rates among infants <6 months \nold with laboratory -confirmed RSV by race and ethnicity, RSV -NET, \n2018 –2019 to 2021 –2022\n▪Hospitalization rates among infants <6 months old differ by race and ethnicity but vary by \nseason \n▪Rates were not adjusted for RSV testing practices and thus may underrepresent RSV \nhospitalization rates but should not affect distributions by race and ethnicity \nRSV-NET: unpublished data. Surveillance was conducted from October –April for the 2018 –19 and 2019 –20 seasons, October –September for the 2020 –21 season, and October –\nSeptember excluding May –June for the 2021 –22 season. Rates were not adjusted for RSV testing practices; testing practices may di ffer by racial and ethnic groups and may have \nchanged over time. Black, White, Asian/Pacific Islander children were categorized as non -Hispanic; Hispanic children could be of any race. \n0246810121416\n2018–2019 2019–2020 2020–2021 2021–2022Rate per 1,000 population\nNon-Hispanic Black Hispanic Non-Hispanic White Non-Hispanic Asian/Pacific Islander\n6001234567\n2018–2019 2019–2020 2020–2021 2021–2022Rate per 1,000 population\nNon-Hispanic Black Hispanic Non-Hispanic White Non-Hispanic Asian/Pacific IslanderPopulation -based ICU admission rates among infants <6 months \nold with laboratory -confirmed RSV by race and ethnicity, RSV -\nNET, 2018 –2019 to 2021 –2022\nRSV-NET: unpublished data. Surveillance was conducted from October –April for the 2018 –19 and 2019 –20 seasons, October –September for the 2020 –21 season, and October –\nSeptember excluding May –June for the 2021 –22 season. Rates were not adjusted for RSV testing practices; testing practices may di ffer by racial and ethnic groups and may have \nchanged over time. Black, White, and Asian/Pacific Islander children were categorized as non -Hispanic; Hispanic children could b e of any race.ICU admission rates among Non -Hispanic Black infants <6 months \nold were 1.2–1.6x higher than among Non -Hispanic White infants\n\n61Seasonal rate of RSV -associated hospitalizations per \n1,000 children among American Indian and Alaska \nNative children <5 years of age, Nov 2019 -May 2020 \n(SuNA )*\n*Hartman et al, RSV2022 12thInternational Symposium, Belfast 9/29/2022 -10/2/2022; Atwell et al. RSV among American Indian and Alaska Native children: 2019 -20 \n(manuscript in press) SuNA = RSV Surveillance among Native American Persons\n**Incidence of RSV -associated hospitalization in 2019 -2020 included for comparison. NVSN = New Vaccine Surveillance Network.\nAge  Chinle, Arizona   Whiteriver, \nArizona  Anchorage, Alaska  Yukon -Kuskokwim \nDelta, Alaska  NVSN** for \ncomparison  \n0-5 Months  83.0 (52.0, 132.5)  70.4 (36.3, 136.6)  35.7 (20.4, 62.6)  132.3 (98.2, 178.1)  21.6 (20.0 , 23.3)  \n6-11 Months  61.6 (35.9, 105.8)  90.1 (50.0, 162.3)  0.0 (0.0, 10.8)  91.6 (64.0, 131.0)  8.2 (7.1 , 9.3) \n0-11 Months  71.8 (50.4, 102.4)  80.6 (51.9, 125.2)  19.2 (11.2, 33.0)  112.2 (89.3, 141.0)  14.9 (13.9 , 16.0)  \n12-23 Months  42.1 (27.2, 65.3)  38.7 (22.0, 68.1)  15.6 (8.7, 27.7)  26.4 (16.6, 41.8)  4.5 (3.9 , 5.2) \n24-59 Months  10.9 (6.8, 17.4)  8.2 (4.2, 16.0)  1.1 (0.3, 3.8)  5.9 (3.2, 10.9)  1.2 (1.2 , 1.5) \n0-59 Months  27.2 (21.4, 34.4)  25.4 (18.7, 34.5)  7.7 (5.3, 11.1)  32.7 (26.9, 39.7)  4.6 (4.3, 4.8) \n \n62Insurance coverage for vaccinations among pregnant \npeople\n▪All ACIP -recommended vaccinations are covered without cost -sharing for adults in \nthe Affordable Care Act (ACA) adult group who receive all essential health benefits1\n▪Beginning on October 1, 2023, coverage of all approved ACIP -recommended adult \nvaccines and vaccine administration, without cost sharing, will be mandatory for \nboth Medicaid and the Children’s Health Insurance Program under section 11405 of \nthe Inflation Reduction Act (IRA) (Pub. L. 117 -169). \n▪Currently, most state Medicaid agencies cover at least some ACIP -recommended \nadult immunizations for those not subject to essential health benefits, but may not \ncover all recommended vaccines.\n1 Quality of Care Vaccines | Medicaid\n63Medicaid coverage among pregnant people\n▪By federal law, all states provide Medicaid coverage for pregnancy -\nrelated services to pregnant women with incomes up to 138% of the \nfederal poverty level1\n▪In 2020, 42.0% of mothers had Medicaid at the time of birth2\n▪In 2020, about 1 in 9 (11.6%) women of childbearing age (aged 15 -44 \nyears) was uninsured in the United States3\n1 Medicaid Coverage for Women | KFF\n2 Medicaid coverage of births: United States, 2020 | PeriStats | March of Dimes\n3 Uninsured women: United States, 2010 -2020 | PeriStats | March of Dimes\n64Equity\n▪What would be the impact of Pfizer Maternal RSVPreF vaccine on \nhealth equity?\nReduced\nProbably reduced\nProbably no impact\nProbably increased\nIncreased\nVaries\nDon’t know\nSummary\n66Evidence to Recommendations (EtR) Framework\nEtR Domain Question(s) Work Group Judgements\nPublic Health Problem Is the problem of public health importance? Yes\nBenefits and Harms How substantial are the desirable anticipated effects? Moderate to large\nHow substantial are the undesirable anticipated effects? Small vs Don’t Know\nDo the desirable effects outweigh the undesirable effects? Favors intervention vs Unclear\nValues Does the target population feel the desirable effects are large \nrelative to the undesirable effects?Probably Yes\nIs there important variability in how patients value the \noutcome?Probably important \nuncertainty or variability \nAcceptability Is the intervention acceptable to key stakeholders? Probably yes or Yes\nFeasibility Is the intervention feasible to implement? Probably yes \nResource Use Is the intervention a reasonable and efficient allocation of \nresources?Probably yes \nEquity What would be in the impact of the intervention on health \nequity?Probably increased \n67Evidence to Recommendations Framework \nSummary: Work Group Interpretations\nBalance of \nConsequencesUndesirable\nconsequences\nclearly\noutweigh\ndesirable\nconsequences\nin most \nsettingsUndesirable\nconsequences\nprobably\noutweigh\ndesirable\nconsequences\nin most settingsThe balance\nbetween\ndesirable\nand \nundesirable\nconsequences\nis closely\nbalanced or\nuncertainDesirable\nconsequences\nprobably\noutweigh\nundesirable\nconsequences\nin most settingsDesirable\nconsequences\nclearly\noutweigh\nundesirable\nconsequences\nin most settingsThere\nis insufficient\nevidence\nto determine\nthe balance of\nconsequences\nMinority Opinion\n68Evidence to Recommendations Framework \nSummary: Work Group Interpretations\nType of \nRecommendationWe do not \nrecommend the \ninterventionWe recommend the \nintervention for \nindividuals based on \nshared clinical \ndecision -makingWe recommend the \nintervention\nMinority Opinion\n69Summary of WG interpretations \n▪Efficacious vaccine that can prevent RSV lower respiratory tract infection in \nyoung infants\n▪WG expressed concern that the Pfizer trial was underpowered to detect a \n20% difference in preterm births between vaccine and placebo recipients\n▪Interpretation of these overarching themes varied:\n–Some members of the WG expressed concern that the data were insufficient to \ndetermine the safety of this vaccine \n–Others stressed this vaccine can provide benefit by preventing RSV lower \nrespiratory tract infection in infants and the difference in preterm births was \nnot statistically significant\n70Summary of WG interpretations (cont.) \n▪Imbalance in preterm birth was most prominent in a single country, South \nAfrica\n▪Imbalance in preterm births was not seen in high -income countries\n▪Imbalance was still present but less pronounced when comparing \nprevalence of low birth weight\n▪Most preterm births were >30 days after vaccination\n71Summary of WG interpretations (cont.) \n▪WG discussed considering a narrower recommended dosing window\n–Some expressed support for starting dosing at a later gestational age within \n24–36-week window used in the trial as this could mitigate potential risk of \nearly preterm birth until additional safety data are available\n–Others expressed concern that this could leave preterm infants who are at \nhigher risk of severe RSV disease unprotected\n▪Aligning RSVpreF vaccine dosing during pregnancy with Tdap \nadministration could improve feasibility\n▪All WG members endorsed the importance of post -introduction vaccine \nsafety monitoring\n72ACIP Policy Question\n▪Should vaccination with Pfizer RSVPreF vaccine (120µg antigen, 1 dose \nIM given 24 –36 weeks gestation) be recommended for pregnant people \nto prevent RSV disease in infants?\nSummary of proposed clinical \nconsiderations for use of Pfizer RSVpreF\nvaccine during pregnancy\n74Proposed clinical considerations: Timing of dosing \nduring pregnancy and simultaneous administration\n▪Proposed dosing interval for RSVpreF vaccine is 24 –36 weeks (aligned with \ntrials)\n▪Healthcare providers could consider aligning RSVpreF vaccine dosing during \npregnancy with Tdap administration for feasibility of implementation \n▪RSVpreF vaccine can be administered with other recommended vaccines \n(e.g., influenza, COVID -19) without regards to timing, including \nsimultaneous vaccination on same clinic day\n75Proposed clinical considerations: Timing of dosing \nduring the year\n▪RSVpreF vaccine should be offered to pregnant people during June -\nFebruary in the continental United States \n▪Healthcare providers can consider offering RSVpreF vaccine year -round \n–For ease of implementation\n–If RSV seasonality is unpredictable\n–In jurisdictions with different RSV seasonality than continental U.S.\n76Proposed clinical considerations: Additional vaccine \ndoses in subsequent pregnancies\n▪Currently there are no data available on\n–Efficacy of the first lifetime dose during subsequent pregnancies\n–Safety of additional doses given in subsequent pregnancies\n▪WG felt that it was too early decide whether additional doses should \nbe given in subsequent pregnancies given the lack of data\n▪Additional data are needed to inform whether additional doses in \nsubsequent pregnancies would be indicated, and recommendations \ncan be updated in the future\n77Acknowledgements \nJefferson Jones\nLauren Roper \nMeredith McMorrow \nMila Prill \nMonica Godfrey \nMichael Melgar\nAmadea Britton\nAmanda Payne \nMegan Wallace\nDanielle Moulia\nMorgan Najdowski \nDavid Hutton \nJamison Pike Andrew Leidner \nIsmael Ortega -Sanchez \nKaren Broder\nNaomi Tepper\nHeidi Moline\nAmber Winn\nMonica Patton\nJenny Milucky\nFiona Havers \nRebecca Morgan \nDoug Campos -Outcalt\nPatricia Wodi\nSascha Ellington\n78Note\nWeacknowledge that not every person who can become pregnant identifies as a \nwoman. Although we try to use gender -neutral language as often as possible, much of \nthe research available currently refers only to “women” when discussing the ability to \nbecome pregnant. When citing research, we refer to the language used in the study. In \nthese cases, “woman” refers to someone who was assigned female at birth. For clarity \nin terminology, “maternal” is used to identify the person who is pregnant or \npostpartum throughout this presentation; the authors are aware that pregnancy is not \nequated with the decision to parent nor do all parents who give birth identify as \nmothers.\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the \nofficial position of the Centers for Disease Control and Prevention.\n\nExtra slides for GRADE\nCenters for Disease Control and Prevention\nGrading of Recommendations, Assessment, \nDevelopment, and Evaluation (GRADE): \nPfizer Maternal RSVPreF Vaccine \nUpdate: May 19, 2023\n82Evidence Retrieval, conducted as of April 10, 2023\nRecords screened*\n(n=161)Duplicates removed\n(n=7)\nStudies irrelevant\n(n=139)Full text studies \nassessed for \neligibility\n(n=12)Studies excluded\n(n=10)\n7 wrong intervention\n3 wrong patient population\nRecords included \nin evidence \nsynthesis \n(n=2)\n*Medline (OVID), Embase (OVID), Cochrane Library, CINAHL ( EbscoHost ), Scopus, clinicaltrials.gov\n83▪High certainty: We are very confident that the true effect lies close to that \nof the estimate of the effect.\n▪Moderate certainty: We are moderately confident in the effect estimate: \nThe true effect is likely to be close to the estimate of the effect, but there is \na possibility that it is substantially different.\n▪Low certainty: Our confidence in the effect estimate is limited: The true \neffect may be substantially different from the effect estimate.\n▪Very low certainty: We have very little confidence in the effect estimate: \nThe true effect is likely to be substantially different from the estimate of \nthe effect.\nNOTE: Evidence type is not measuring the quality of individual studies, but how much certainty we \nhave in the estimates of effect across each outcome.GRADE Evidence Type\n84GRADE Evidence Type\n▪Initial evidence type (certainty level) determined by study design\n–Initial evidence high certainty: A body of evidence from randomized \ncontrolled trials\n–Initial evidence low certainty: A body of evidence from observational \nstudies\n▪The certainty of evidence may be downgraded due to risk of bias, \ninconsistency, indirectness, imprecision, or publication bias. For non -\nrandomized studies, the certainty may be rated up for presence of dose -\nresponse gradient, large or very large magnitude of effect, and opposing \nresidual confounding.\nNOTE: Evidence type is not measuring the quality of individual studies, but how much certainty we \nhave in the estimates of effect across each outcome.\nBenefits\n86Outcome 1: Medically attended RSV -associated lower \nrespiratory tract infection in infants (n=1 study)\n▪ Pfizer phase 3 randomized controlled trial (RCT), MATISSE1\n▪ Trial locations: Argentina, Australia, Brazil, Canada, Chile, Denmark, Finland, Gambia, Japan, Republic of Korea, \nMexico, Netherlands, New Zealand, Philippines, South Africa, Spain, Taiwan, United States\n– 45% of participants from United States\n▪ Study enrollment and efficacy follow -up occurred June 17, 2020, to October 2, 2022\n▪ Data evaluated: data cut -off September 30, 2022; mean follow -up in infant participants 11.97 months after \nbirth (range: 0.0, 24.3)\n▪ Infant evaluable efficacy set: 3,495 in vaccine arm; 3,480 in placebo arm\n▪ Exclusion criteria of certain conditions may not represent all pregnant people and their infants in the United \nStates \n▪ Placebo was not a saline placebo, but a lyophile match to the vaccine consisting of excipients matched to \nthose used in the RSVpreF vaccine formulation, minus the active ingredients\n1Kampmann B, Madhi SA, Munjal I, et al. Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants. N Engl J Med. 2023 Apr 5. doi: 10.1056/NEJMoa2216480.\n87Outcome 1: Medically attended RSV -associated lower \nrespiratory tract infection in infants (n=1 study)\n▪Medically attended visit (inclusive of inpatient and outpatient encounters) and ≥1:\n–Fast breathing: respiratory rate ≥60 bpm (<2 months of age [60 days]) or ≥50 \nbpm (≥2 to 12 months of age)\n–SpO2 measured in room air <95%\n–Chest wall indrawing\n▪Positive validated RT -PCR in central laboratory\n▪Confirmed by endpoint adjudication committee (EAC)\nSpO2= Peripheral capillary oxygen saturation \n88Outcome 1: Medically attended RSV -associated lower \nrespiratory tract infection in infants (n=1 study)\nTime period \nafter birthEvents/Vaccine\n(n/N)Events/Placebo\n(n/N)Vaccine efficacy (1 –RR)\n(95% CI)Manufacturer calculated \nvaccine efficacy1 (99.5% or \n97.58% CI)\n0–90 days after \nbirth224/3495 56/3480 57.3% (31.3, 73.5) 57.1% (14.7, 79.8)\n0–120 days after \nbirth35/3495 81/3480 57.0% (36.2, 71.0) 56.8% (31.2, 73.5)\n0–150 days after \nbirth47/3495 99/3480 52.7% (33.3, 66.5) 52.5% (28.7, 68.9)\n0–180 days after \nbirth57/3495 117/3480 51.5% (33.7, 64.5) 51.3% (29.4, 66.8)\n1Vaccine efficacy was calculated as 1−(P/[1−P]), where P is the number of cases of illness in the RSVpreF group divided by the total number of cases of illness. At 90 days, \n99.5% confidence intervals (CIs) were used (determined by the alpha -spending function and adjusted with the use of the Bonferron i procedure), and at later intervals, 97.58% \nCIs were used (based on a two -sided alpha level of 0.0483 adjusted with the use of the Bonferroni procedure).\n2This outcome did not meet success criterion using manufacturer calculated VE (lower bound of CI was <20%) \n89Outcome 1: Severe Medically attended RSV -associated \nlower respiratory tract infection in infants (n=1 study)\n▪Medically attended visit (inclusive of inpatient and outpatient encounters) and ≥1:\n–Fast breathing (respiratory rate ≥70 (<2 month of age [60 days]) or ≥60 (≥2 to \n12 months of age)\n–SpO2 measured in room air <93%\n–High -flow nasal cannula or mechanical ventilation\n–ICU admission for >4 hours\n–Unresponsive/unconscious\n▪Positive validated RT -PCR in central laboratory\n▪Confirmed by endpoint adjudication committee (EAC)\nSpO2= Peripheral capillary oxygen saturation \n90Outcome 1: Severe Medically attended RSV -associated \nlower respiratory tract infection in infants (n=1 study)\nTime period \nafter birthEvents/Vaccine\n(n/N)Events/Placebo\n(n/N)Vaccine efficacy (1 –RR)\n(95% CI)Manufacturer calculated \nvaccine efficacy1 (99.5% or \n97.58% CI)\n0–90 days after \nbirth6/3495 33/3480 81.9% (56.8, 92.4) 81.8% (40.6, 96.3)\n0–120 days \nafter birth12/3495 46/3480 74.0% (51.1, 86.2) 73.9% (45.6, 88.8)\n0–150 days \nafter birth16/3495 55/3480 71.0% (49.6, 83.4) 70.9% (44.5, 85.9)\n0–180 days \nafter birth19/3495 62/3480 69.5% (49.1, 81.7) 69.4% (44.3, 84.1)\n1Vaccine efficacy was calculated as 1−(P/[1−P]), where P is the number of cases of illness in the RSVpreF group divided by the total number of cases of illness. At 90 days, \n99.5% confidence intervals (CIs) were used (determined by the alpha -spending function and adjusted with the use of the Bonferron i procedure), and at later intervals, 97.58% \nCIs were used (based on a two -sided alpha level of 0.0483 adjusted with the use of the Bonferroni procedure).\n91GRADE: Medically attended RSV -associated lower \nrespiratory infection in infants (n=1 study)\n▪Measures of effect\n–Relative Risk: 0.487 (0.332, 0.706)\n–Absolute Risk1: 17 fewer per 1,000 (10 to 22 fewer); NNV: 59 (45, 100)\n–Absolute Risk2: 119 fewer per 1,000 (68 to 154 fewer); NNV: 8 (6, 15)\n–Absolute Risk3: 56 fewer per 1,000 (32 to 73 fewer); NNV: 18 (14, 31)\n▪Concerns in certainty assessment: None\n▪Evidence type: High\n1Calculated using the observed outcomes in the placebo arm during the clinical trial follow -up (3.4%)\n2Calculated using rate from Lively 2019 JPIDS , 2004 -2009 from 3 New Vaccine Surveillance Network (NVSN) sites from Nov -Apr season, \nincluded if with acute respiratory infection (ARI), not restricted to LRTI. \n3Calculated assuming 47.5% of ARI from Lively et al paper were LRTI ( Rainisch 2020 Vaccine )\nNNV= Number needed to vaccinate\n92Outcome 2: Hospitalization for RSV -associated lower \nrespiratory tract infection in infants (n=1 study)\n▪Phase 3 RCT, MATISSE1\n▪A respiratory tract infection due to RSV that results in hospitalization\n▪Confirmed by endpoint adjudication committee (EAC)\n1Kampmann B, Madhi SA, Munjal I, et al. Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants. N Engl J Med. 2023 Apr 5. doi: 10.1056/NEJMoa2216480.\n93Outcome 2: Hospitalization for RSV -associated lower \nrespiratory tract infection in infants (n=1 study)\nTime period after \nbirthEvents/Vaccine\n(n/N)Events/Placebo\n(n/N)Vaccine efficacy (1 –RR)\n(95% CI)Manufacturer calculated \nvaccine efficacy1\n(99.17% CI)\n0–90 days after birth 10/3495 31/3480 67.9% (34.6, 84.2) 67.7% (15.9, 89.5)\n0–120 days after \nbirth15/3495 37/3480 59.6% (26.6, 77.8) 59.5% (8.3, 83.7)\n0–150 days after \nbirth17/3495 39/3480 56.6% (23.4, 75.4) 56.4% (5.2, 81.5)\n0–180 days after \nbirth19/3495 44/3480 57.0% (26.5, 74.8) 56.8% (10.1, 80.7)\n0–360 days after \nbirth238/3495 57/3480 33.6% (0.2, 55.8) 33.3% ( -17.6, 62.9)\n1Vaccine efficacy was calculated as 1 –(P/[1 –P]), where P is the number of cases in the RSVpreF group divided by the total number of cases. The confidence interval was \nadjusted using the Bonferroni procedure and accounting for the primary endpoints results. As a secondary endpoint, the criter ionfor vaccine efficacy was a\nlower bound of the confidence interval >0%.\n2This outcome did not meet success criterion using manufacturer calculated VE (lower bound of CI was <0%) \n94GRADE: Hospitalization for RSV -associated lower \nrespiratory tract infection in infants (n=1 study)\n▪Measures of effect\n–Relative risk: 0.432 (0.193, 0.899)\n–Absolute risk1: 7 fewer per 1,000 (1 to 10 fewer); NNV: 143 (100, 1,000)\n–Absolute risk2: 11 fewer per 1,000 (2 to 15 fewer); NNV: 91 (67, 500) \n▪Concerns in certainty assessment: \n–Serious concern for imprecision due to the width of the confidence interval \ncontaining estimates for which different policy decisions might be \nconsidered\n▪Evidence type: Moderate\n1Absolute risk was calculated using the observed outcomes in the placebo arm during the available clinical trial follow -up. \n2Calculated using the rate of acute respiratory infection (ARI) hospitalizations for infants 0 -5 months (2016 -2020 NVSN, unpubli shed)  \n95Outcome 5: RSV -associated death in infants (n=2 \nstudies)\n▪Phase 3 RCT, MATISSE and Phase 2b RCT (unpublished, data obtained from manufacturer)\n▪Phase 2b RCT1,2\n–Pregnant people ages 18 –49 in Argentina, Chile, South Africa and United States\n•Infant safety set: 114 in vaccine arm (phase 3 formulation); 116 in placebo arm\n▪1 RSV -associated death occurred in an infant in the placebo group recorded at day 120 after \nbirth in the Phase 3 study, no RSV -associated deaths occurred in the RSVPreF group\n▪No RSV -associated deaths were recorded in the Phase 2b study among those who received \nthe phase 3 formulation or placebo\n▪Outcome not included in GRADE\n1Simões EAF, Center KJ, Tita ATN, et al. Prefusion F Protein –Based Respiratory Syncytial Virus Immunization in Pregnancy. N Engl J Med. 2022 Apr 28. doi: \n10.1056/NEJMoa2106062.\n2https://www.clinicaltrials.gov/ct2/show/study/NCT04032093\n96Outcome 6: All -cause medically attended lower \nrespiratory tract infection in infants (n=1 study)\n▪Phase 3 RCT, MATISSE1\n▪Infant with any medically attended -RTI visit (inpatient or outpatient) AND\n–Fast breathing (respiratory rate ≥60 bpm for <2 months of age [<60 \ndays of age] or ≥50 bpm for ≥2 to <12 months of age) OR\n–SpO2 <95% OR\n–Chest wall indrawing\n1Kampmann B, Madhi SA, Munjal I, et al. Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants. N Engl J Med. 2023 Apr 5. doi: 10.1056/NEJMoa2216480.SpO2= Peripheral capillary oxygen saturation \n97Outcome 6: All -cause medically attended lower \nrespiratory tract infection in infants (n=1 study)\nTime period \nafter birthEvents/Vaccine\n(n/N)Events/Placebo\n(n/N)Vaccine efficacy \n(1 –RR) (95% CI)Manufacturer calculated \nvaccine efficacy1  (99.17% CI)\n0–90 days after \nbirth2186/3495 200/3480 7.4% ( -12.4, 23.7) 7.0% ( -22.3, 29.3)\n0–120 days after \nbirth2261/3495 278/3480 6.5% ( -10, 20.5) 6.1% ( -18.3, 25.5)\n0–150 days after \nbirth2331/3495 349/3480 5.6% ( -8.9, 18.1) 5.2% ( -16.5, 22.8)\n0–180 days after \nbirth2392/3495 402/3480 2.9% ( -10.7, 14.8) 2.5% ( -17.9, 19.4)\n0–360 days after \nbirth2504/3495 531/3480 5.5% ( -5.8, 15.5) 5.1% ( -12.1, 19.6)\n1Vaccine efficacy was calculated as 1 –(P/[1 –P]), where P is the number of cases in the RSVpreF group divided by the total number of cases. The confidence interval was \nadjusted using the Bonferroni procedure and accounting for the primary endpoints results. As a secondary endpoint, the criter ionfor vaccine efficacy was a\nlower bound of the confidence interval >0%.\n2This outcome did not meet success criterion (lower bound of CI was <0%) \n98GRADE: All-cause medically attended lower respiratory \ntract infection in infants (n=1 study)\n▪Measures of effect\n–Relative risk: 0.975 (0.806, 1.179)\n–Absolute risk*: 3 fewer per 1,000 (22 fewer to 21 more)\n▪Concerns in certainty assessment\n–Serious concern for imprecision due to the width of the confidence \ninterval containing estimates for which different policy decisions might \nbe considered\n▪Evidence type: Moderate\n*Absolute risk was calculated using the observed outcomes in the placebo arm during the available clinical trial follow -up. Abso lute risk estimates should be \ninterpreted in this context.\nHarms\n100Outcome 8: Serious adverse events in pregnant people \n(n=2 studies)\n▪Phase 3 RCT, MATISSE (unpublished, data obtained directly from \nmanufacturer)\n–Maternal safety set: 3,682 participants in vaccine arm; 3,675 in \nplacebo arm\n▪Phase 2b RCT (unpublished, data obtained directly from manufacturer)\n–Maternal safety set: 115 participants in vaccine arm (phase 3 \nformulation); 117 in placebo arm\n▪Follow up times for serious adverse events reported by maternal \nparticipants were from vaccination through 6 months after delivery (Phase \n3) or throughout the study (Phase 2b)\n101Outcome 8: Serious adverse events in pregnant people \n(n=2 studies)\n101Trial Events/Vaccine\n(n/N)Events/Placebo\n(n/N)Relative Risk (95% CI)\nPhase 3 598/3682 (16.2%) 558/3675 (15.1%) 1.07 (0.96, 1.19)\nPhase 2b 7/115 (6.1%) 14/117 (12.0%) 0.51 (0.21, 1.21)\nSerious adverse events in four vaccine recipients (pain in an arm followed by bilateral lower extremity pain, premature labor , \nsystemic lupus erythematosus, and eclampsia) and in one placebo recipient (premature placental separation) were assessed by t he \ninvestigator as being related to the injection. Based on review of the event narratives and temporal association of these events to\nvaccination, FDA agreed with the investigator’s assessments that there was a reasonable possibility that these events were re lated \nto the study intervention.\nVaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Briefing Document -FDA\n102GRADE: Serious adverse events in pregnant people \n(n=2 studies)\n▪Measures of effect\n–Relative risk: 1.06 (0.95, 1.17)\n–Absolute risk*: 9 more per 1,000 (8 fewer to 26 more)\n▪Concerns in certainty assessment\n–Serious concern for imprecision due to the width of the confidence \ninterval containing estimates for which different policy decisions might \nbe considered\n▪Evidence type: Moderate\n*Absolute risk was calculated using the observed outcomes in the placebo arm during the available clinical trial follow -up. Abso lute risk estimates should be \ninterpreted in this context.\n103Outcome 9: Reactogenicity (grade 3+) in pregnant \npeople (n=2 studies)\n▪Phase 3 RCT, MATISSE and Phase 2b (unpublished, data obtained directly \nfrom manufacturer)\n▪Participants reported local and systemic reactions up to 7 days after \nvaccination\n104Outcome 9: Reactogenicity (grade 3+) in pregnant \npeople \n104Trial Outcome Events/Vaccine\n(n/N)Events/Placebo\n(n/N)Relative Risk (95% CI)\nPhase 3 Local events (grade 3+) 11/3660 (0.3%) 0/3639 (0%) 22.87 (1.35, 387.94)\nSystemic events (grade 3+) 83/3663 (2.3%) 83/3640 (2.3%) 0.94 (0.70, 1.28)\nPhase 2b Local events (grade 3+) 0/114 (0%) 0/117 (0%) 1.03 (0.02, 51.28)\nSystemic events (grade 3+) 2/114 (1.8%) 4/117 (3.4%) 0.51 (0.10, 2.75)\nGrade 3: prevents daily routine activity. For redness or swelling is >10 cm. For vomiting, requires intravenous hydration. Fo r \ndiarrhea, includes 6 or more loose stools in 24 hours. Grade 4: requires emergency room visit or hospitalization; for redness\nincluded necrosis or exfoliative dermatitis; for swelling included necrosis. \n\n105Outcome 9: Reactogenicity (grade 3+) in pregnant \npeople (n=2 studies)\n▪Measures of effect\n–Relative risk: 0.97 (0.72, 1.31)\n–Absolute risk*:  1 fewer per 1,000 (6 fewer to 7 more)\n▪Concerns in certainty assessment: \n–Serious concern for indirectness as this data only includes systemic \nreactions \n▪Evidence type: Moderate\n*Absolute risk was calculated using the observed outcomes in the placebo arm during the available clinical trial follow -up. Abso lute risk estimates should be \ninterpreted in this context.\n106Outcome 10: Serious adverse events in infants (n=2 \nstudies)\n▪Phase 3 RCT, MATISSE (unpublished, data obtained directly from \nmanufacturer)\n–Infant safety set: 3,568 in vaccine arm; 3,558 in placebo arm\n▪Phase 2b RCT (unpublished, data obtained directly from manufacturer)\n–Infant safety set: 114 in vaccine arm (phase 3 formulation); 116 in \nplacebo arm\n107\nOutcome 10: Serious adverse events in infants (n=2 \nstudies)\nTrial Events/Vaccine\n(n/N)Events/Placebo\n(n/N)Relative Risk (95% CI)\nPhase 3 625/3568 (17.5%) 623/3558 (17.5%) 1.00 (0.90, 1.11)\nPhase 2b 41/114 (36.0%) 38/116 (32.8%) 1.10 (0.77, 1.57)\nNo serious adverse events in infants were considered by the investigators to be related to the vaccine. For infant deaths in the\nRSVpreF group, the FDA agreed with the investigator’s conclusions for 4 out of 5 of the infant deaths; however, for 1 case of\nextreme prematurity in an infant born to an 18 -year -old mother at 10 days after vaccination who died from prematurity -related \ncomplications, FDA was unable to exclude the possibility of the extreme prematurity and subsequent death being related to rec eipt \nof the investigational product. No non -fatal SAEs in infant participants were considered related to maternal vaccination by FDA.\nVaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Briefing Document -FDA\n108GRADE: Serious adverse events in infants (n=2 studies)\n▪Measures of effect\n–Relative risk: 1.01 (0.91, 1.11)\n–Absolute risk*:  2 more per 1,000 (16 fewer to 19 more)\n▪Concerns in certainty assessment\n–Serious concern for imprecision due to the width of the confidence \ninterval containing estimates for which different policy decisions might \nbe considered\n▪Evidence type: Moderate\n*Absolute risk was calculated using the observed outcomes in the placebo arm during the available clinical trial follow -up. Abso lute risk estimates should be \ninterpreted in this context.\n109Outcome 11: Preterm births (n=2 studies)\n▪Phase 3 RCT, MATISSE and Phase 2b (unpublished, data obtained directly \nfrom manufacturer)\n–Gestational age at birth <37 weeks and <34 weeks\n110Outcome: Preterm births (n=2 studies), Pfizer maternal \nRSVpreF vaccine\n110Publication Definition Events/Vaccine\n(n/N)Events/Placebo\n(n/N)Relative Risk (95% CI)\nPhase 3<34 weeks 21/3568 12/3558 1.75 (0.86, 3.54)\n<37 weeks 201*/3568 169/3558 1.19 (0.97, 1.45)\nPhase 2b<34 weeks 0/115 1/117 0.34 (0.01, 8.24)\n<37 weeks 6/115 3/117 2.03 (0.52, 7.94)\n*When reported as an adverse event of special interest, 202 preterm births occurred in the vaccine arm; the relative risk is minimally changed at 1.19 (0.98, 1.45) when using this count\n111Outcome: Preterm births (n=2 studies), Pfizer maternal \nRSVpreF vaccine\n▪Measures of effect\n–Relative risk: 1.20 (0.99, 1.46)\n–Absolute risk*:  9 more per 1,000 (from 0 fewer to 22 more)\n▪Concerns in certainty assessment:\n–Very se rious concern for imprecision due to the width of the \nconfidence interval containing estimates for which different policy \ndecisions might be considered and not meeting optimal information \nsize requirements\n▪Evidence type: Low\n*Absolute risk was calculated using the observed outcomes in the placebo arm during the available clinical trial follow -up. Abso lute risk estimates should be \ninterpreted in this context.\nGRADE additional slides\n113Inclusion/exclusion criteria for pregnant people -Phase 3 Trial\nInclusion Exclusion\nHealthy women ≤49 years of age who are \nbetween 24 0/7 and 36 0/7 weeks of gestation \non the day of planned vaccination, with an \nuncomplicated, singleton pregnancy, who are at \nno known increased risk for complications.\nWilling and able to comply with scheduled visits, \ntreatment plan, laboratory tests, and other \nstudy procedures.\nReceiving prenatal standard of care based on \ncountry requirements.\nHad a fetal anomaly ultrasound examination \nperformed at ≥18 weeks of pregnancy with no \nsignificant fetal abnormalities observed.\nDetermined by medical history, physical \nexamination, and clinical judgment to be \nappropriate for inclusion in the study.\nDocumented negative HIV antibody test, syphilis \ntest, and hepatitis B virus (HBV) surface antigen \ntest during this pregnancy and prior to \nrandomization (Visit 1).\nIntention to deliver at a hospital or birthing \nfacility where study procedures can be obtained.\nExpected to be available for the duration of the \nstudy and can be contacted by telephone during \nstudy participation.\nParticipant is willing to give informed consent \nfor her infant to participate in the study.\nCapable of giving signed informed consent \nwhich includes compliance with the \nrequirements and restrictions listed in the \ninformed consent document (ICD) and in this \nprotocol OR If the maternal participant is \nilliterate, a thumbprinted informed consent \nmust be obtained, which must be signed and \ndated by an impartial witness who was present \nthroughout the entire informed consent process \nconfirming that the maternal participant has \nbeen informed of all pertinent aspects of the \nstudy.Prepregnancy body mass index (BMI) of >40 kg/m2. If prepregnancy BMI is not available, the BMI at the time of the first obste tric visit during the current pregnancy may be used.\nBleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindi cate intramuscular injection.\nHistory of severe adverse reaction associated with a vaccine and/or severe allergic reaction (eg, anaphylaxis) to any compone nt of the investigational product or any related vaccine.\nCurrent pregnancy resulting from in vitro fertilization.\nCurrent pregnancy complications or abnormalities at the time of consent that will increase the risk associated with the parti cipation in and completion of the study, including but not limited \nto the following:\nPreeclampsia, eclampsia, or uncontrolled gestational hypertension.\nPlacental abnormality.\nPolyhydramnios or oligohydramnios.\nSignificant bleeding or blood clotting disorder.\nEndocrine disorders, including untreated hyperthyroidism or untreated hypothyroidism. This also includes disorders of glucose intolerance (eg, diabetes mellitus type 1 or 2) antedating \npregnancy or occurring during pregnancy if uncontrolled at the time of consent.\nAny signs of premature labor with the current pregnancy or having ongoing intervention (medical/surgical) in the current preg nancy to prevent preterm birth.\nPrior pregnancy complications or abnormalities at the time of consent, based on the investigator's judgment, that will increa se the risk associated with the participation in and completion of \nthe study, including but not limited to the following:\nPrior preterm delivery ≤34 weeks' gestation.\nPrior stillbirth or neonatal death.\nPrevious infant with a known genetic disorder or significant congenital anomaly.\nMajor illness of the maternal participant or conditions of the fetus that, in the investigator's judgment, will substantially increase the risk associated with the maternal or infant participant's \nparticipation in, and completion of, the study or could preclude the evaluation of the maternal participant's response (inclu despositive serologic testing for regional endemic conditions \nassessed during routine maternal care, as per local standards of care and obstetric recommendations).\nCongenital or acquired immunodeficiency disorder, or rheumatologic disorder or other illness requiring chronic treatment with known immunosuppressant medications, including \nmonoclonal antibodies, within the year prior to enrollment.\nOther acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation o r behavior or laboratory abnormality that may increase the risk \nassociated with study participation or investigational product administration or may interfere with the interpretation of stu dy results and, in the judgment of the investigator, would make \nthe participant inappropriate for entry into this study.\nParticipation in other studies involving investigational drug(s) within 28 days prior to consent and/or during study particip ation.\nReceipt of monoclonal antibodies within the year prior to enrollment or the use of systemic corticosteroids for >14 days with in 28 days prior to study enrollment. Permitted treatments \ninclude the receipt of severe acute respiratory syndrome coronavirus 2 (SARS -CoV-2) monoclonal antibodies, prednisone doses of < 20 mg/day for ≤14 days and, inhaled/nebulized, intra -\narticular, intrabursal, or topical (skin or eyes) corticosteroids.\nCurrent alcohol abuse or illicit drug use. Note: Marijuana use is not considered an exclusion criterion for the study when el icited in participant screening, though it may be considered illicit \nin some locales.\nReceipt of blood or plasma products or immunoglobulin (Ig), from 60 days before investigational product administration, or pl anned receipt through delivery, with 1 exception, Rho(D) \nimmune globulin (eg, RhoGAM), which can be given at any time.\nPrevious vaccination with any licensed or investigational RSV vaccine or planned. Note: Licensed COVID -19 vaccines or COVID -19 vaccines authorized for temporary or emergency use will \nnot be prohibited during the course of this study.\nInvestigator site staff members directly involved in the conduct of the study and their family members, site staff members ot herwise supervised by the investigator, or Pfizer employees, \nincluding their family members, directly involved in the conduct of the study.\nParticipants who are breastfeeding at the time of enrollment.\n114Inclusion/exclusion criteria for infants -Phase 3 Trial\nInclusion Exclusion\nEvidence of a signed and dated informed consent document signed by the \nparent(s)/legal guardian(s) OR If the infant participant's maternal \nparticipant/parent(s)/legal guardian(s) is illiterate, a thumbprinted \ninformed consent must have been obtained, which must have been signed \nand dated by an impartial witness who was present throughout the entire \ninformed consent process confirming that the maternal \nparticipant/parent(s)/legal guardian(s) has been informed of all pertinent \naspects of the study for herself (maternal participant) and her fetus/infant \nprior to taking part in the study.\nParent(s)/legal guardian(s) willing and able to comply with scheduled visits, \ntreatment plan, laboratory tests, and other study procedures.Infant who is a direct descendant (e.g., child or \ngrandchild) of the study personnel.\n115Inclusion/exclusion criteria for pregnant people -Phase 2b\nInclusion -Pregnant people Exclusion -Pregnant people\nHealthy women 18 to 49 years of age between 24 \nand 36 weeks of gestation on the day of planned \nvaccination, with an uncomplicated pregnancy, who \nare at no known increased risk for complications, and \nwhose fetus has no significant abnormalities \nobserved on ultrasound.\nWilling and able to comply with scheduled visits, \ntreatment plan, laboratory tests, and other study \nprocedures.\nReceiving prenatal standard of care.\nHad an ultrasound performed at >=18 weeks of \npregnancy.\nHad a negative urinalysis for protein and glucose at \nthe screening visit. Trace protein in the urine is \nacceptable if the blood pressure is also normal.\nDetermined by medical history, physical examination, \nscreening laboratory assessment, and clinical \njudgment to be appropriate for inclusion in the study.\nDocumented negative human immunodeficiency \nvirus antibody, hepatitis B virus surface antigen, \nhepatitis C virus antibody, and syphilis tests at the \nscreening visit.\nBody mass index of </=40 kg/m2 at the time of the \nscreening visit.\nCapable of giving signed informed consent, which \nincludes compliance with the requirements and \nrestrictions listed in the informed consent document \nand in this protocol.\nExpected to be available for the duration of the study \nand willing to give informed consent for her infant to \nparticipate in the study.Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindi cate \nintramuscular injection.\nHistory of severe adverse reaction associated with a vaccine and/or severe allergic reaction to any component of the investig ational product \nor any related vaccine.\nHistory of latex allergy.\nHistory of any severe allergic reaction.\nParticipants with known or suspected immunodeficiency.\nCurrent pregnancy resulting from in vitro fertilization or other assisted reproductive technology.\nA prior history of or known current pregnancy complications or abnormalities that will increase the risk associated with the participant's \nparticipation in and completion of the study.\nMajor illness of the mother or conditions of the fetus that, in the investigator's judgment, will substantially increase the risk associated with \nthe participant's participation in, and completion of, the study or could preclude the evaluation of the participant's respon se.\nParticipant with a history of autoimmune disease or an active autoimmune disease requiring therapeutic intervention including but not \nlimited to systemic or cutaneous lupus erythematosus, autoimmune arthritis/rheumatoid arthritis, Guillain -Barré syndrome, multip le \nsclerosis, Sjögren's syndrome, idiopathic thrombocytopenia purpura, glomerulonephritis, autoimmune thyroiditis, giant cell ar teritis \n(temporal arteritis), psoriasis, and insulin -dependent diabetes mellitus (type 1).\nOther acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation o r behavior or \nlaboratory abnormality that may increase the risk associated with study participation or investigational product administrati on or may \ninterfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inapp ropriate for entry \ninto this study.\nParticipation in other studies involving investigational drug(s) within 28 days prior to study entry and/or during study part icipation.\nParticipants who receive treatment with immunosuppressive therapy including cytotoxic agents or systemic corticosteroids (suc h as for \ncancer or an autoimmune disease), or planned receipt of such treatment or agents during study participation. If systemic cort icosteroids have \nbeen administered short term (<14 days) for treatment of an acute illness, participants should not be enrolled into the study until \ncorticosteroid therapy has been discontinued for at least 30 days before investigational product administration. Inhaled/nebu lized, intra \narticular, intrabursal, or topical (skin or eyes) corticosteroids are permitted.\nCurrent alcohol abuse or illicit drug use.\nReceipt of blood or plasma products or immunoglobulin, from 60 days before investigational product administration, or planned receipt \nthrough delivery, with 1 exception, Rho(D) immune globulin (eg, RhoGAM), which can be given at any time.\nPrevious vaccination with any licensed or investigational RSV vaccine or planned receipt during study participation.\nLaboratory test results at the screening visit outside the normal reference value for pregnant women according to their trime ster in \npregnancy.\nParticipants who are breastfeeding at the time of the screening visit.\n116Inclusion/exclusion criteria for infants -Phase 2b\nInclusion -Infants Exclusion -Infants\nEvidence of a signed and dated informed consent document signed \nby the parent(s).\nParent(s) willing and able to comply with scheduled visits, \ntreatment plan, laboratory tests, and other study procedures.Infant who is a direct descendant (eg, child or grandchild) of the \nstudy personnel.\n117\nFigure 1. Enrollment, \nRandomization, Administration of \nVaccine or Placebo, and Follow -up\nKampmann B, Madhi SA, Munjal I, et al. \nBivalent Prefusion F Vaccine in \nPregnancy to Prevent RSV Illness in \nInfants. N Engl J Med. 2023 Apr 5. doi: \n10.1056/NEJMoa2216480.\n118Table 1. Demographics of phase 3 trial\n118\nKampmann B, Madhi SA, Munjal I, et al. \nBivalent Prefusion F Vaccine in \nPregnancy to Prevent RSV Illness in \nInfants. N Engl J Med. 2023 Apr 5. doi: \n10.1056/NEJMoa2216480.\n119Severity scale for local reactions and systemic events \n(maternal participants)\n119\nKampmann B, Madhi SA, Munjal I, et al. Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants. N Engl J Med. 2023 Apr 5. doi: 10.1056/NEJMoa2216480.\n120Studies Included in the Review of Evidence\nLast name first author, \nPublication yearStudy design Country Age \nmean \n(SD)Total Population N intervention N comparison Outcomes Funding \nSource\nKampmann B, \netal.plus unpublished \ndata obtained directly \nfrom the manufacturer RCT Argentina, Australia, \nBrazil, Canada, Chile, \nDenmark, Finland, \nGambia, Japan, \nRepublic of Korea, \nMexico, Netherlands, \nNew Zealand, \nPhilippines, South \nAfrica, Spain, Taiwan, \nUnited States29.0 \n(5.7)7,357 3,682 3,675 Medically attended \nRSV-associated lower \nrespiratory infection in \ninfants; Hospitalization \nfor RSV -associated \nlower respiratory tract \ninfection in infants; \nRSV-associated death \nin infants; All cause \nmedically attended \nlower respiratory tract \ninfection in infants; \nSerious adverse events \nin pregnant people; \nReactogenicity in \npregnant people; \nSerious adverse events \nin infants; Preterm \nbirthPfizer\nPfizer, Phase 2 Trial \nplus unpublished data \nobtained directly from \nthe manufacturer RCT Argentina, Chile, South \nAfrica and the United \nStates27.1\n(5.2)232 115 (phase 3 \nformulation)117 RSV-associated death \nin infants; Serious \nadverse events in \npregnant people; \nReactogenicity in \npregnant people;\nSerious adverse events \nin infants; Preterm \nbirth;Pfizer\n121Summary of Studies Reporting Outcome 1: Medically attended \nRSV-associated lower respiratory infection in infants \nLast name \nfirst author, \nPublication \nyearAge \nmean \n(SD)N \ninterventionN \ncomparisonComparator \nVaccineAbsolute \ndifference/effect \nestimate (99.58% \nCI)Study \nlimitations \n(Risk of Bias)\nKampmann B, \net al.29.0\n(5.7)3495 3480 Placebo 17 fewer per \n1,000 (10 to 22 \nfewer)None\n122Summary of Studies Reporting Outcome 2: Hospitalization for \nRSV-associated lower respiratory tract infection in infants  \nLast name first \nauthor, \nPublication \nyearAge \nmean \n(SD)N \ninterventionN \ncomparisonComparator \nVaccineAbsolute \ndifference/effect \nestimate (99.17% \nCI)Study \nlimitations \n(Risk of Bias)\nKampmann B, \net al.29.0 \n(5.7)3495 3480 Placebo 7 fewer per 1,000 \n(1 to 10 fewer)None\n123Summary of Studies Reporting Outcome 5: RSV -\nassociated death in infants \nLast name first \nauthor, \nPublication \nyearAge \nmean \n(SD)N \ninterventionN \ncomparisonComparator \nVaccineAbsolute \ndifference/effe\nct estimateStudy \nlimitations \n(Risk of Bias)\nKampmann B, et \nal.29.0\n(5.7)3495 3480 Placebo Not estimable \n1 death in a \nplacebo \nrecipientN/A\nPhase 2b RCT, \nunpublished18-49 \n(range)114 116 Placebo Not estimable \n0 deaths in trialN/A\n124Summary of Studies Reporting Outcome 6: All cause medically \nattended lower respiratory tract infection in infants \nLast name first \nauthor, \nPublication \nyearAge \nmean \n(SD)N \ninterventionN \ncomparisonComparator \nVaccineAbsolute \ndifference/effect \nestimate (99.17% \nCI)Study \nlimitations \n(Risk of Bias)\nKampmann B, et \nal.29.0 \n(5.7)3495 3480 Placebo 3 fewer per 1,000 \n(22 fewer to 21 \nmore)None\n125Summary of Studies Reporting Outcome 8: Serious \nadverse events in pregnant people \nLast name first \nauthor, \nPublication \nyearAge \nmean \n(SD)N \ninterventionN \ncomparisonComparator \nVaccineAbsolute \ndifference/effect \nestimateStudy \nlimitations \n(Risk of Bias)\nKampmann B, et \nal.29.0 \n(5.7)3682 3675 Placebo RR: 1.07 (0.96, \n1.19)None\nPhase 2b RCT 27.1\n(5.2)115 117 Placebo RR: 0.51 (0.21, \n1.21)None\n126Summary of Studies Reporting Outcome 9: \nReactogenicity (grade 3+) in pregnant people \nLast name first \nauthor, \nPublication \nyearAge \nmean \n(SD)N \ninterventio\nnN \ncomparisonComparator \nVaccineAbsolute \ndifference/effect \nestimateStudy \nlimitations \n(Risk of Bias)\nKampmann B, \net al.29.0 \n(5.7)3663 3640 Placebo RR: 0.94 (0.70, \n1.28)None\nPhase 2b RCT 27.1\n(5.2)114 117 Placebo RR: 0.51 (0.10, \n2.75)None\n127Summary of Studies Reporting Outcome 10: Serious \nadverse events in infants \nLast name first \nauthor, Publication \nyearAge median \n(range)N intervention N comparison Comparator \nVaccineAbsolute \ndifference/effect \nestimateStudy \nlimitations (Risk \nof Bias)\nKampmann B, et \nal. 11.97 \nmonths \n(0.0, 24.3) 3568 3558 Placebo RR: 1.00 (0.90, \n1.11)None\nPhase 2b RCT 114 116 Placebo RR: 1.10 (0.77, \n1.57)None\n128Summary of Studies Reporting Outcome 11: Preterm \nbirth\nLast name first \nauthor, Publication \nyearAge mean \n(SD)N intervention N comparison Comparator \nVaccineAbsolute \ndifference/effect \nestimateStudy \nlimitations (Risk \nof Bias)\nKampmann B, et \nal.11.97 \nmonths \n(0.0, 24.3)3568 3558 Placebo RR: 1.19 (0.97, \n1.45)None\nPhase 2b RCT 115 117 Placebo RR: 2.03 (0.52, \n7.94)None\n129Grade Summary of Findings Table -Benefits\n129№ of \nstudiesStudy designRisk of \nbiasInconsistency Indirectness ImprecisionOther \nconsiderationsIntervention ComparisonRelative\n(95% CI)Absolute\n(95% CI)Importance Certainty\nMedically attended RSV -associated lower respiratory infection in infants\n1 Randomized \nstudiesNot serious Not serious Not serious Not serious None 57/3495 (1.6%) 117/3480 \n(3.4%)0.487 \n(0.332, \n0.706)17 fewer \nper 1,000 \n(10 to 22 \nfewer)Critical High\n23.1% 119 fewer \nper 1,000 \n(68 to 154 \nfewer)\n11.0% 56 fewer \nper 1,000 \n(32 to 73 \nfewer)\nHospitalizations RSV -associated lower respiratory infection in infants\n1 Randomized \nstudiesNot serious Not serious Not serious Serious None 19/3495 (0.5%) 44/3480 (1.3%) 0.432 \n(0.193, \n0.899)7 fewer per \n1,000 (1 to \n10 fewer)Critical Moderate\n1.9% 11 fewer \nper 1,000 (2 \nto 15 fewer)\nAll-cause medically attended lower respiratory infection in infants\n1 Randomized \nstudiesNot serious Not serious Not serious Serious None 392/3495 \n(11.2%)402/3480 \n(11.6%)0.97 (0.85, \n1.11)3 fewer per \n1,000 (22 \nfewer to 21 \nmore)Important Moderate\n130Grade Summary of Findings Table -Harms\n130№ of \nstudiesStudy design Risk of biasInconsiste\nncyIndirectness ImprecisionOther \nconsiderationsIntervention comparisonRelative\n(95% CI)Absolute\n(95% CI)Importance Certainty\nSerious adverse events in pregnant women\n2 Randomized \nstudiesNot \nseriousNot \nseriousNot serious Serious None 605/3797 \n(15.9%)572/3792 \n(15.1%)1.06 \n(0.95, \n1.17)9 more per \n1,000 (8 \nfewer to 26 \nmore)Critical Moderate\nReactogenicity (3+ or higher) in pregnant women\n2 Randomized \nstudiesNot \nseriousNot \nseriousSerious Not serious None 85/3777 \n(2.3%)87/3757 \n(2.3%)0.97 \n(0.72, \n1.31)1 fewer per \n1,000 (6 \nfewer to 7 \nmore)Important Moderate\nSerious adverse events in infants\n2 Randomized \nstudiesNot \nseriousNot \nseriousNot serious Serious None 625/3568 \n(17.5%)623/3558 \n(17.5%)1.01 \n(0.91, \n1.11)2 more per \n1,000 (16 \nfewer to 19 \nmore)Critical Moderate\nPreterm birth\n2 Randomized \nstudiesNot \nseriousNot \nseriousNot serious Very \nseriousNone 207/3683 \n(5.6%)172/3675 \n(4.7%)1.20 \n(0.99, \n1.46)9 more per \n1,000 (0 \nfewer to 22 \nmore)Critical Low", "summary": "Centers for Disease Control and Prevention Evidence to Recommendations Framework:  Pfizer Maternal RSVpreF Vaccine Katherine Fleming -Dutra, MD Co-Lead, Respiratory Syncytial Virus Vaccines -Pediatric/Maternal Work Group  Coronavirus and Other Respiratory Viruses Division National Center for Immunization and Respiratory Diseases June 22, 2023 2Evidence to Recommendations (EtR) Framework Policy Question ▪Should vaccination with Pfizer RSVPreF vaccine (120µg antigen, 1 dose  IM given 24 –36…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/03-RSV-Mat-Ped-Fleming-Dutra-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 130}
{"title": "04 RSV Mat Ped Hutton 508", "content": "Economics of combined use of Pfizer \nmaternal RSVpreF vaccine and \nnirsevimab\nDavid W. Hutton, PhD, MS\nAssociate Professor, Health Management and Policy, School of Public Health\nAssociate Professor of Global Public Health, School of Public Health\nAssociate Professor, Industrial and Operations Engineering, College of Engineering\nUniversity of MichiganPresentation to the ACIP \nJune 22, 2023\n\nResearch team\nUniversity of Michigan\n•David Hutton, PhD\n•Lisa Prosser, PhD\n•Angela Rose, MPH\n•Kerra Mercon , MSCDC\n•Jefferson Jones, MD, MPH, FAAP\n•Mila Prill, MSPH\n•Meredith McMorrow, MD, MPH, \nFAAP\n•Jamison Pike, PhD\n•Katherine Fleming -Dutra, MD, \nFAAP\n•Ismael Ortega -Sanchez, PhD\n•Fiona Havers, MD\n•Betsy Gunnels, MSPH\n•Andrew Leidner , PhD\n2\nConflicts of interest statements\n•Authors have no known conflict of interests.\n3\nMethods: Study questions\n•Determine the cost -effectiveness of:\n•Nirsevimab in children born to mothers who received RSVpreF at least 2 \nweeks prior to delivery\n•RSVpreF for pregnant persons who will give nirsevimab to their newborns\n•Single individual\n•Evaluate by month of year\n•Perspective: Societal\n•Timeframe: 1 year (1 RSV season)\n•Analytic horizon: infant’s lifetime\n•Discount rate: 3%\n4\nOverview of nirsevimab\nchanges/additions\n•Since February\n•Nirsevimab cost $500/dose\n•Nirsevimab reduces palivizumab use\n•Old base case ICER: $ 102,805/QALY \n•New base case ICER: $157,537/QALY\n5\nMethods: Intervention effectiveness\n•NO evidence of efficacy on the combined use of \nthese products\n•Assumption:\n•Efficacy equal to the highest of nirsevimab or RSVpreF :\n•Efficacy would not be higher than from the most effective \nproduct\n6\nMethods: Intervention effectiveness\n7* Assuming administration of nirsevimab at birth0%20%40%60%80%100%\n0 2 4 6 8 10 12 14Hospitalization Efficacy\nMonths since birth\nRSVPreF Both Nirsevimab\nIncremental benefit of adding \nnirsevimab on top of RSVpreF\n8•For infants of persons vaccinated with RSVpreF\nduring pregnancy\n0%20%40%60%80%100%\n0 2 4 6 8 10 12 14Hospitalization Efficacy\nMonths since birth\nRSVPreF Both NirsevimabMethods: Intervention effectiveness\n9\nAdditional benefit of adding nirsevimab\n* Assuming administration of nirsevimab at birth\n\n0%10%20%30%40%50%60%70%80%90%100%\n0 2 4 6 8 10 12Hospitalization Efficacy\nMonth\nBoth RSVpreF OnlyMethods: Intervention effectiveness\nExample: Off -peak (Aug) birth\nAdditional benefit of adding nirsevimab\nNote: Peak infections are typically Dec -Feb\n 10\n110.0%5.0%10.0%15.0%20.0%25.0%30.0%\nApr May Jun Jul Aug Sep Oct Nov Dec Jan Feb MarFraction of Annual Infections\nSource: National Respiratory and Enteric Virus Surveillance System (NREVSS) (2015 -2019)Reminder: Seasonality\nResults: Incremental benefit of adding \nnirsevimab on top of RSVpreF\nNirsevimab given in Oct -Mar\nICER= Incremental cost effectiveness ratio ($/QALY)Birth Month $- $500,000 $1,000,000 $1,500,000 $2,000,000 $2,500,000 $3,000,000ICER ($/QALY)\n12\nResults: Adding nirsevimab to all \ninfants born to vaccinated mothers\nNirsevimab given at birth for infants born October -March, and in October/November for infants born in April through \nSeptember\n13\nResults: Adding nirsevimab to all \ninfants born to vaccinated mothers\nNirsevimab given at birth for babies born October -March, and in October/November for babies born in April through \nSeptember\n14\nResults: Adding nirsevimab to all \ninfants born to vaccinated mothers\nQALYs \nGainedAdditional \nCostsICER\n($/QALY)\n0.000781 $522.12 $  668,735 \nNotes: Nirsevimab given at birth for babies born October -March, and in October/November for babies born in April \nthrough September\nICER= Incremental cost effectiveness ratio; QALY= Quality -adjusted life -year\n15\nResults: Adding nirsevimab only for \ninfants born during Apr -Sept\nNirsevimab given in October/November for babies born in April through September born to mothers who received \nRSVpreF\n16\nNirsevimab given in October/November for babies born in April through September born to mothers who received \nRSVpreFResults: Adding nirsevimab only for \ninfants born during Apr -Sept\n17\nNirsevimab given in October/November for babies born in April through September born to mothers who received \nRSVpreF\nICER= Incremental cost effectiveness ratio; QALY= Quality -adjusted life -yearQALYs \nGainedAdditional \nCostsICER\n($/QALY)\n0.001032 $502.40 $486,882 Results: Adding nirsevimab only for \ninfants born during Apr -Sept\n18\n•Marginal additional benefit beyond RSVpreF\nprotection\n•ICER is very highSummary: Incremental benefit of \nadding nirsevimab on top of RSVpreF\n19\nIncremental benefit of adding RSVpreF\non top of nirsevimab\n20\n0%20%40%60%80%100%\n0 2 4 6 8 10 12 14Hospitalization Efficacy\nMonths since birth\nRSVPreF Both NirsevimabMethods: Intervention effectiveness\n21\nAdditional benefit of adding RSVpreF\n* Assuming administration of nirsevimab at birth\n0%10%20%30%40%50%60%70%80%90%100%\n0 2 4 6 8 10 12Hospitalization Efficacy\nMonth\nBoth Nirsevimab OnlyMethods: Intervention effectiveness\nexample: Off -peak (Aug) birth\nAdditional benefit of adding RSVpreF\n22\nResults: Incremental benefit of adding \nRSVpreF on top of nirsevimab\nBirth Month $- $1 $2 $3 $4 $5 $6 $7 $8 $9 $10ICER ($ Millions)\nICER= Incremental cost effectiveness ratio23\n•Very marginal additional benefit beyond \nNirsevimab protection\n•ICERs are extremely highSummary: Incremental benefit of \nadding RSVpreF on top of nirsevimab\n24\n•Limitation:\n•No efficacy data for combination of products\n•Combinations of RSVpreF and Nirsevimab add \nmarginal effectiveness at very high cost in the \ngeneral populationOverall summary: Combinations\n25\nThank You\n•Please send comments to:\n•dwhutton@umich.edu\n26\nAppendix\n27\nAdditional Input \nAssumptions\n28\nMethods: Provision of Nirsevimab\n•Base case:\n•At birth for those born \n•October 1 –March 31\n•October for those born in \n•April (~6 -month visit)\n•June (~4 -month visit)\n•August (~2 -month visit)\n•November for those born in\n•May (~6 -month visit)\n•July (~4 -month visit)\n•September (~2 -month visit)\n29\nMethods: Intervention effectiveness\n30•Assuming Administration of Nirsevimab at birth\n•MA-LRTI= medically attended lower respiratory tract infection0%20%40%60%80%100%\n0 2 4 6 8 10 12 14MA-LRTI Efficacy\nMonths since birth\nRSVPreF Nirsevimab Both\nAdditional combination \nResults\nIncremental benefit of adding on \nnirsevimab top of RSVpreF\nResults: Incremental benefit of adding \nnirsevimab on top of RSVpreF\nby month of birth\nBirth Month0.0000.0100.0200.0300.0400.0500.0600.070\nOutpatient ED Inpatient ICU Inpatient Day ICU DayEvents Averted per Birth\nOctober November December January February March\nApril May June July August September0.0000.0010.0010.002\nICU\nNirsevimab given at birth for babies born October -March, and in October/November for babies born in April through September\nResults: Incremental benefit of adding \nnirsevimab on top of RSVpreF\nBirth Month0100200300400500600700800900\nOutpatient ED InpatientNumber Needed to Immunize to Avoid One...\nNovember December January February March April\nMay June July August September01000200030004000\nICU Inpatient\nDayICU Day\nNirsevimab given at birth for babies born October -March, and in October/November for babies born in April through September\nResults: Incremental benefit of adding \nnirsevimab on top of RSVpreF\nBirth Month $- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000 $450,000 $500,000\nOutpatient ED InpatientCost per Event Averted\nOctober November December January February March\nApril May June July August September $- $500,000 $1,000,000 $1,500,000 $2,000,000 $2,500,000\nICU Inpatient\nDayICU Day\nNirsevimab given at birth for babies born October -March, and in October/November for babies born in April through September\nIncremental benefit of adding RSVpreF\non top of nirsevimab\n00.00050.0010.00150.0020.00250.0030.00350.0040.00450.005\nOutpatient ED Inpatient ICU Inpatient Day ICU DayEvents Averted per Birth\nOctober November December January February March\nApril May June July August SeptemberResults: Incremental benefit of adding \nRSVpreF on top of nirsevimab\nImpact of adding RSVpreF in addition \nto nirsevimab is bigger for births in \nApril -Sept since nirsevimab does not \nprovide protection in April -Sept for \nthose born in those months \nBirth Month\nResults: Incremental benefit of adding \nRSVpreF on top of nirsevimab\nBirth Month010002000300040005000600070008000900010000\nOutpatient ED Inpatient ICU Inpatient Day ICU DayNumber Needed to Immunize to Avoid One...\nOctober November December January February March\nApril May June July August September\nResults: Incremental benefit of adding \nRSVpreF on top of nirsevimab\nBirth Month $- $100,000 $200,000 $300,000 $400,000 $500,000 $600,000 $700,000 $800,000 $900,000 $1,000,000\nOutpatient ED Inpatient ICU Inpatient Day ICU DayCost per Event Averted \nOctober November December January February March\nApril May June July August September\nResults: Adding RSVpreF\nWhat if RSV season is early?\n•Scenario:\n•RSVpreF provided in off -peak\n•RSV season starts 2 months early\n•Nirsevimab still provided in October\n0.0%10.0%20.0%30.0%\nApr Jun Aug Oct Dec FebIncidence\n(% of annual)Seasonality\nOriginal Model\n$6.86 \n$2.72 \n$2.25 \n$0.71 \n$1.42 \n$0.43 \n $- $2.00 $4.00 $6.00 $8.00 $10.00ICER ($ Millions)ICER (Millions)Results: Adding RSVpreF\nWhat if RSV season is early?\nICERs improve, but still \nvery expensive\nBirth Month\nICER -Incremental cost -effectiveness ratio\nNirsevimab base case \nupdate\nNirsevimab results: Base case\n43•Base case:\n•Population of 1,000 births\n•50% uptake in the nirsevimab group\n•First RSV season\n•$500/dose\n•Nirsevimab only impacts LRTI\nLTRI= Lower respiratory tract infection\nResults: Health outcomes\n44Cohort:1,000 nirsevimab and 1,000 natural history, assuming 50% uptake in nirsevimab group\nURTI -Upper respiratory tract infection; LRTI -Lower respiratory tract infection - 50 100 150 200 250\n Natural\nHistory Nirsevimab  Natural\nHistory Nirsevimab  Natural\nHistory Nirsevimab\nMedically attended\noutpatientEmergency Department InpatientNumber of Events in Cohort\nURTI LRTI\nResults: Health outcomes\n45Cohort:1,000 nirsevimab and 1,000 natural history, assuming 50% uptake in nirsevimab group29.3\n10.4\n3.9\n0.921.1\n2.6\n0.05.010.015.020.025.030.035.0\nOutpatient ED Inpatient ICU Inpatient Day ICU DayEvents Averted per 1000 births\nNirsevimab\nResults: Health outcomes\n4617 48 128 581 \n24 194 \n - 100 200 300 400 500 600 700\nOutpatient ED Inpatient ICU Inpatient Day ICU DayNumber needed to Prophylax to avoid\nNirsevimab\nResults: Costs\n47Base costs of nirsevimab : $500/dose, Cost of palivizumab for high -risk included in “Natural History”Cohort:1,000 births, assuming 50% uptake in nirsevimab group$0$100,000$200,000$300,000$400,000$500,000$600,000\nNatural History\nNirsevimab\nNatural History\nNirsevimab\nNatural History\nNirsevimab\nNatural History\nNirsevimab\nNatural History\nNirsevimab\nNatural History\nNirsevimab\nIntervention Outpatient ED Inpatient Deaths TotalTotal Costs in Cohort\nMedical Productivity\nResults: Health outcomes\n48Base costs of nirsevimab : $500/dose$3,794 $10,650 $28,372 $128,963 \n$5,254 $42,988 \n $- $20,000 $40,000 $60,000 $80,000 $100,000 $120,000 $140,000\nOutpatient ED Inpatient ICU Inpatient Day ICU DayCost per Event Averted\nNirsevimab\nResults: QALYs lost\n49Adverse \nEventsOutpatient ED Inpatient Deaths Total Grand\nChild Caregiver Child Caregiver Child Caregiver Child Child Caregiver Total\nNatural \nHistory 1.95 0.98 0.90 0.45 0.22 0.09 0.15 3.22 1.51 4.73 \nNirsevimab 0.01 1.70 0.85 0.76 0.38 0.15 0.06 0.10 2.73 1.29 4.03 \nCohort:1,000 births, assuming 50% uptake in nirsevimab group\nResults: Cost -effectiveness\n50Cohort:1,000 births, assuming 50% uptake in nirsevimab group $- $100,000 $200,000 $300,000 $400,000 $500,000 $600,000\n (4.80)  (4.60)  (4.40)  (4.20)  (4.00)  (3.80)Costs \nQALYs (lost) from RSV \nNatural History Nirsevimab\nBase costs of nirsevimab : $500/dose, Cost of palivizumab for high -risk included in “Natural History”\nResults: Cost -effectiveness\n51OverallCosts ($) QALYsICER ($/QALY)\nVs. NH\nNatural History 418,556 4.73 \nNirsevimab 529,597 4.03 157,537 \nCohort:1,000 births, assuming 50% uptake in nirsevimab group\nBase costs of nirsevimab : $500/dose, Cost of palivizumab for high -risk included in “Natural History”\nSensitivity: Tornado nirsevimab\n52Base cost of $500/dose$0 $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000\nnirsevimab cost/dose\nDisease-specific inpatient costs (per inpatient case)  Age 0-5 months\nRSV QALYS Lost\nInitial Efficacy\nRSV-related QALYs lost Outpatient Child\nFraction Receiving Palivizumab Natural History\nRSV-related QALYs lost Outpatient Child caregiver\nProportion of RSV infections with an LRTI diagnosis Outpatient Age 0-5 months\nDisease-specific inpatient costs (per inpatient case)  Age 6-11 months\nRSV-related QALYs lost ED  ChildIncremental Cost -Effectiveness Ratio\nLow High\n $- $50,000 $100,000 $150,000 $200,000 $250,000\n$0 $100 $200 $300 $400 $500 $600ICER\nTotal Cost of Nirsevimab (drug + administration)Sensitivity: Cost nirsevimab\n53Base cost of $500/dose\nScenario: Upper respiratory infection \neffect\n5455.4\n17.1\n3.9\n0.921.1\n2.6\n0.010.020.030.040.050.060.0\nOutpatient ED Inpatient ICU Inpatient Day ICU DayEvents Averted per 1000 births\nNirsevimab\n $- $20,000 $40,000 $60,000 $80,000 $100,000 $120,000 $140,000\n$0 $100 $200 $300 $400 $500 $600ICER\nTotal Cost of Nirsevimab (drug + administration)Scenario: Upper respiratory infection \neffect\n55 Nirsevimab is assumed to be equally efficacious in preventing upper respiratory tract infections as lower respiratory tract infections.\nScenario: Timing analysis\n56•Cost -effectiveness of an infant receiving nirsevimab \nas a newborn in \n•Oct-Feb\n•Oct-March\n•Oct-April\n•With varying efficacy in months 6 -10\n•0%\n•25%\n•50%\nCohort:1,000 nirsevimab and 1,000 natural history, assuming 50% uptake in nirsevimab group\n57Scenario: Timing and efficacy in months 6 -10\nSlightly lower ICERs for Oct -MarBase cost of $500/dose\nICER= Incremental cost -effectiveness ratioCohort:1,000 nirsevimab and 1,000 \nnatural history, assuming 50% uptake in \nnirsevimab group $- $20,000 $40,000 $60,000 $80,000 $100,000 $120,000 $140,000 $160,000 $180,000\n0% efficacy 25% efficacy 50% efficacyICER\nOct-Feb Oct-Mar Oct-Apr", "summary": "Economics of combined use of Pfizer  maternal RSVpreF vaccine and  nirsevimab David W. Hutton, PhD, MS Associate Professor, Health Management and Policy, School of Public Health Associate Professor of Global Public Health, School of Public Health Associate Professor, Industrial and Operations Engineering, College of Engineering University of MichiganPresentation to the ACIP  June 22, 2023  Research team University of Michigan •David Hutton, PhD •Lisa Prosser, PhD •Angela Rose, MPH •Kerra…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/04-RSV-Mat-Ped-Hutton-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 57}
{"title": "05 RSV Mat Ped Jones 508", "content": "Centers for Disease Control and Prevention\nClinical considerations for RSVpreF maternal vaccine \nand nirsevimab\nJefferson Jones MD MPH FAAP\nCDR USPHS\nCo-Lead, Respiratory Syncytial Virus Vaccines -Pediatric/Maternal \nWork Group\nCoronavirus and Other Respiratory Viruses Division\nNational Center for Immunization and Respiratory Diseases\nJune 22, 2023\n2Policy questions for ACIP vote\n▪Should vaccination with Pfizer RSVPreF vaccine (120µg antigen, 1 dose IM given 24 -\n36 weeks gestation) be recommended for pregnant people to prevent RSV disease \nin infants?\n▪Should one dose of nirsevimab be recommended for infants born during or \nentering their first RSV season and <8 months of age at time of immunization?\n▪Should one dose of nirsevimab be recommended for children who are at increased \nrisk of severe RSV disease entering their second RSV season and <20 months of age \nat time of immunization?\n3Potential advantages of maternal vaccination versus a \nmonoclonal antibody (mAb)\n▪ A maternal vaccine may be lower in price \n▪ A mAb is not a traditional vaccine and many issues may complicate implementation\n–Insurance coverage, vaccine schedule, immunization registries, safety monitoring\n▪ Maternal vaccine provides protection from birth, when infants are at highest risk\n–A mAb must be timed correctly to provide protection during the RSV season, and atypical RSV \ntransmission may lead to unprotected infants\n▪ Maternal vaccine induces a polyclonal antibody response, which should be more resilient to \nmutations than a monoclonal antibody\n–Evidence suggests that mutations resulting in nirsevimab resistance are rare, but naturally \noccurring resistant mutations have been detected1,2\n–Mutations resulted in poor efficacy of a previous mAb product ( suptavumab )3\n1 Abram IDweek 2022. 2 Abram 12th RSV International Symposium 2022. 3Simões CID 2021 . \n4Potential advantages of mAb over maternal \nvaccination\n▪Imbalance for preterm birth observed after RSVpreF vaccine vs. placebo in maternal clinical \ntrials, but not statistically significant1\n▪No head -to-head trials comparing efficacy, but protection from maternal vaccination likely \nwanes more quickly1–4\n▪Estimated half-lifein nirsevimab trials\n–Nirsevimab : 63–73 days​5,6\n–Infection -induced maternal RSV antibodies: 36 –38 days5\n▪Nirsevimab administration can be timed to be given when infant is entering RSV season\n1 Kampmann NEJM 2023 . 2 Muller NEJM 2023 . 3Madhi NEJM 2020 . 4Nunes F1000Res 2018 . 5Wilkins Nat Med 2023 . 6Griffin NEJM 2020 .\n5Potential advantages of mAb over maternal \nvaccination (continued)\n▪Protection from maternal vaccination relies on sufficient transplacental transfer of \nantibodies, which may be reduced in\n–Infants born soon after maternal immunization1\n–Infants born premature2\n–Maternal disease2\n▪Maternal uptake of flu and Tdap vaccines lower than routine childhood vaccines3,4 \n–Unclear if pregnant people willing to accept multiple vaccines during pregnancy\n–However, flu vaccine uptake among children only mildly higher than among pregnant \npeople\n–Uptake of maternal RSVpreF vaccine and nirsevimab unknown\n1https://www.cdc.gov/vaccines/pregnancy/vacc -during -after.html. 2Palmerira Clin Dev Immunol 2012 . \n3https://www.cdc.gov/flu/fluvaxview/pregnant -women -apr2022.htm. 4Hill MMWR 2023\n6Benefits of both products being available\n▪Each product has certain advantages\n▪Parental preferences may differ, as suggested by survey asking pregnant people \nabout product preference if both available1\n–28% only maternal vaccine\n–25% only RSV antibody injection\n–38% both\n▪Some populations lack access or do not present for prenatal care, precluding \nmaternal vaccination\n▪Scenarios may exist for which use of both products may be warranted to maximize \nprotection from RSV -associated severe disease–8% none\n–1% other\n1 Unpublished CDC and University of Iowa/RAND survey of 523 people currently pregnant or pregnant within last 12 \nmonths of survey conducted December 21, 2022 -January 2, 2023\n7Cost effectiveness summary\n▪Cost effectiveness of giving nirsevimab if mother had been vaccinated\n–$668,735/QALY if given to all infants\n–$486,882/QALY if given to infants born April to September\n▪Cost effectiveness of giving RSVpreF to mother if nirsevimab will be \ngiven\n–More than $10,000,000/QALY on average\n8Challenges if nirsevimab recommendations relate to \nmaternal vaccination status\n▪Maternal vaccination status might be unknown\n▪Transferring documentation of maternal vaccination to the healthcare \nprovider of infant may be difficult\n–Limited information available during birth hospitalization\n–Less information regarding receipt of prenatal vaccinations may be \navailable to infant primary care providers\n9Draft clinical considerations if both RSVpreF and \nnirsevimab are licensed and recommended\n▪Either maternal vaccination with RSVpreF or nirsevimab is recommended to \nprevent RSV disease, but both products are not needed for most infants\n▪Risks and benefits of both RSVpreF and nirsevimab should be considered \nwhen deciding on maternal vaccination\n▪If mother vaccinated, nirsevimab can be considered if infant considered to \nhave insufficient protection from vaccine or is at high risk of severe disease\n10Scenarios to consider administration of nirsevimab\nwhen mother has been vaccinated\n▪Receipt of maternal vaccine not confirmed by healthcare record\n▪Infant born within 14 days of vaccination\n▪Infant born premature\n▪Healthcare provider recommends maximizing protection because infant at \nhigh risk of severe disease\n–Especially important if born >3 months prior to peak of RSV season\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the \nofficial position of the Centers for Disease Control and Prevention.", "summary": "Centers for Disease Control and Prevention Clinical considerations for RSVpreF maternal vaccine  and nirsevimab Jefferson Jones MD MPH FAAP CDR USPHS Co-Lead, Respiratory Syncytial Virus Vaccines -Pediatric/Maternal  Work Group Coronavirus and Other Respiratory Viruses Division National Center for Immunization and Respiratory Diseases June 22, 2023 2Policy questions for ACIP vote ▪Should vaccination with Pfizer RSVPreF vaccine (120µg antigen, 1 dose IM given 24 - 36 weeks gestation) be…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/05-RSV-Mat-Ped-Jones-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 11}
{"title": "01 mpox Sanchez 508", "content": "National Center for Emerging and Zoonotic Infectious Diseases\nMpox Vaccine Work Group\nACIP Meeting\nJune 23, 2023\nPablo Sanchez MD\nThe Ohio State University−Nationwide Children’s Hospital\nChair, ACIP Mpox Work Group\nMpox outbreaks\n▪Before 2022, rare outside of Africa\n▪In Africa, have involved 2 clades:\n–Clade I (previously Congo Basin Clade)\n–Clade II (previously West African Clade)\n▪In United States, have involved Clade II\n–Clade IIa:  2003 U.S. outbreak associated with pet prairie dogs\n–Clade IIb:  2022/2023 global outbreak associated with male -to-male \nsexual contact\n▪Historically: Clade I believed to be associated with more severe disease \nthan Clade II\nSevere manifestations observed in severely \nimmunocompromised persons during the 2022/2023 outbreak:  \nClade IIb\nCarrubba S, Geevarghese A, Solli E et al. Novel severe oculocutaneous manifestations of human \nmonkeypox virus infection and their historical analogues. Lancet Infect Dis. 2023 Jan 23:S1473-\n3099(22)00869-6. \nMenezes YR, Miranda AB. Severe disseminated clinical \npresentation of monkeypox virus infection in an \nimmunosuppressed patient: first death report in Brazil. Rev Soc \nBras Med Trop. 2022 Aug 29;55:e0392. \nACIP recommendations\n▪\n▪\n▪\n–\n–With global eradication of smallpox, routine vaccinations against \northopoxviruses were no longer needed\nRoutine smallpox vaccinations stopped globally in 1980 (USA, 1972)\nACIP recommendations for persons at occupational risk for orthopoxvirus\ninfections since 1980\nLargest proportion of people recommended to be vaccinated are \nresearch laboratorians who work with orthopoxviruses (including \nmonkeypox virus [MPXV])\nACAM2000 and JYNNEOS are the vaccines recommended\nCurrent ACIP recommendations for persons at risk for \noccupational exposure:  ACAM2000 and JYNNEOS\n▪Since 2015, ACAM2000 recommended \n▪In November 2021, JYNNEOS recommended as alternative to ACAM2000\n\nACAM2000 compared to JYNNEOS\nVaccine virus\nAdministrationVia multiple percutaneous puncture \ntechnique (single dose)Subcutaneously* via 2 vaccine doses, \n28 days apartvirus\nTakeInadvertent inoculation and \nautoinoculation can occur via vaccine \nsite lesionNo risk of inadvertent inoculation \nand autoinoculation with vaccinia \nvirus\n*During the 2022/2023, intradermal was the preferred route of administration; vaccine effectiveness data \nindicates this route has been equally effective \nvirusACAM2000\nLive, replication competent vaccinia Live, replication deficient vaccinia JYNNEOS\nContraindications for ACAM2000 and JYNNEOS\n\n2022/2023 U.S. mpox outbreak:  JYNNEOS \nrecommended\n▪\n▪Fewer contraindications and adverse events with JYNNEOS\nBefore this outbreak, no real -world experience with JYNNEOS\nhttps://www.cdc.gov/poxvirus/mpox/vaccines/index.html\nShort-term goal of the Work Group\n▪\n▪Currently no ACIP recommendation for use of JYNNEOS during mpox\noutbreaks\nDevelop ACIP recommendations for use of JYNNEOS during mpox\noutbreaks*\n*Public health authorities determine whether there is an mpox outbreak; a single case may be \nconsidered an mpox outbreak at the discretion of public health authorities. Other circumstances in \nwhich a public health response may be indicated include ongoing risk of introduction of mpox into a \ncommunity due to disease activity in another geographic area.\nFebruary 2023 ACIP meeting:  Vote passed for use of \nJYNNEOS during outbreaks\nACIP recommends the 2-dose* JYNNEOS vaccine series for persons \naged 18years and older at risk of mpox during an mpox outbreak§\n*Dose 2 administered one month after dose 1\n§Public health authorities determine whether there is an mpox outbreak; a single case may be \nconsidered an mpox outbreak at the discretion of public health authorities. Other circumstances \nin which a public health response may be indicated include ongoing risk of introduction of mpox\ninto a community due to disease activity in another geographic area.\nTimeline that was proposed during February 2023*\nMpox outbreaks: Use of 2-\ndose JYNNEOS for persons \naged ≥ 18 years\nFebruary 2023 June 2023 October 2023-Mpox outbreaks: Use of 2-dose JYNNEOS\nfor persons aged <18 years \n-Updates about vaccine effectiveness and \nsafetyConsider need for longer term \nvaccination strategy for 2-dose \nJYNNEOS\n*These votes do not impact existing recommendations for the current mpox outbreak. \n§https://www.cdc.gov/poxvirus/monkeypox/interim -considerations/overview.html\nAgenda for today’s meeting\n▪Updates about epidemiology, vaccine safety, and vaccine effectiveness \nduring the ongoing outbreak:  Faisal Minhaj\n▪Clinical guidance about the use of 2 -dose JYNNEOS (subcutaneous) series \nduring mpox outbreaks:  Agam Rao\n▪Considerations for long -term protection against mpox :  Discussion in the \ncontext of the ongoing outbreak:  Agam Rao\nTentative timeline for ACIP discussions and votes\nACIP meeting: Clinical \nguidance about use of \nJYNNEOS during outbrea\nJune 2023kPublication of MMWR \nabout use of JYNNEOS \nduring mpox outbreaks\nAugust/September 2023ACIP meeting: Consider need\nfor longer term vaccination \nstrategy for 2-dose JYNNEOS\nOctober 2023 Current US mpox vaccination strategy remains active:  Populations at high \nCurrent U.S. risk mposhox vaculd cinacontiontinue t strategy o be v remains accina in etedffect*\n*MMWR publication will not change the clinical guidance posted for the ongoing outbreak: \nhttps://www.cdc.gov/poxvirus/monkeypox/interim -considerations/overview.html\nWG members\nACIP Member\nPablo Sánchez\nBeth Bell \nEx Officio and Liaison Members\nCSTE: Chris Hahn / Paul Cieslak\nASTHO: Ericka McGowan\nNACHO: Philip Huang\nFDA: Sixun Yang, Clement \nMeseda & Alonzo García\nACOG: Howard Minkoff\nAAP: Jim CampbellAIM: Rob Schechter / Jane Zucker\nAPHL:  Jafar Razeq\nNIH: Janet Lathey / Kimberly Taylor \nIHS: Matthew Clark\nNACI: Nicole Forbes / Oliver Baclic\nIDSA: Shireesha Dhanireddy / Rajesh Gandhi\nInvited Consultants\nSubject matter experts: Inger Damon, Stuart \nIsaacs, Mike Merchlinsky & Amanda \nZarrabian (HHS/BARDA)\nClinician experts in STIs, HIV, pediatrics, \nmaternal vaccination, vaccine safety, health \nequity, smallpox vaccination strategies, \noccupational health\nClinician experts\nSTIs, HIV, and mpox\n(adult and peds):\nJason Zucker\nJeanne Marrazzo\nPablo Tebas\nVince Marconi\nKim Workowski\nBonnie Maldonado\nImmunizations (including for special \npopulations) and vaccine safety:\nRuth Karron\nFlor Munoz -Rivas\nKathy EdwardsHealth equity, vaccination strategies \nincluding for smallpox:\nJoel Breman\nGerard Vong\nOccupational Medicine and worker safety:\nMark Russi\nCDC contributors\nMpox epi, lab, and vaccine experts\nBrett Petersen\nAndrea McCollum\nChristy Hutson\nLaboratory Response Network:\nJulie Villanueva\nInfection control, worker safety:\nMarie de Perio\nDavid Kuhar\nSpecial populations (e.g., Persons \nexperiencing homelessness)\nEmily MositesVaccine safety\nMichael McNeil\nJonathan Duffy\nRegulatory Affairs\nYon Yu\nSTIs and HIV\nLaura Bachmann\nLeandro Mena\nJohn Brooks \nAlexa OsterDrug Services\nJulian Jolly\nVaccine \nimplementation\nLiz Velasquez\nJames Lee\nDoD Liaison to CDC\nAlan Lam\nWork group lead  \nAgam Rao\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the \nofficial position of the Centers for Disease Control and Prevention.Thank you!", "summary": "National Center for Emerging and Zoonotic Infectious Diseases Mpox Vaccine Work Group ACIP Meeting June 23, 2023 Pablo Sanchez MD The Ohio State University−Nationwide Children’s Hospital Chair, ACIP Mpox Work Group Mpox outbreaks ▪Before 2022, rare outside of Africa ▪In Africa, have involved 2 clades: –Clade I (previously Congo Basin Clade) –Clade II (previously West African Clade) ▪In United States, have involved Clade II –Clade IIa:  2003 U.S. outbreak associated with pet prairie dogs –Clade…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/01-mpox-Sanchez-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 17}
{"title": "02 mpox Minhaj 508", "content": "National Center for Emerging and Zoonotic Infectious Diseases\nUpdates from the 2022 –2023 U.S. Mpox Outbreak: \nEpidemiology, Vaccine Safety, and Vaccine \nEffectiveness\nACIP Meeting\nJune 23, 2023Faisal Syed Minhaj, PharmD, MPH, DABAT\nEpidemic Intelligence Service Officer\nPoxvirus and Rabies Branch\nUnited States Mpox Case Counts April 2022 –June 2023\nhttps://www.cdc.gov/poxvirus/mpox/response/2022/mpx -trends.html\nUnited States Mpox Case Counts January 1 –June 6, 2023\nUptick in \ncases in \nChicago\nhttps://www.cdc.gov/poxvirus/mpox/response/2022/mpx -trends.html\nMpox cases reported to CDC by age and gender May \n2022 –June 14, 2023\nhttps://www.cdc.gov/poxvirus/mpox/response/2022/demographics.htmlData were available for 98.9% of cases \nreported to CDC\nMpox cases reported to CDC by race and ethnicity May \n2022 –June 14, 2023\n56      1050    8859   11782  5289   1894     753     340      196       64        71        42        81        10    Count within columns\nhttps://www.cdc.gov/poxvirus/mpox/response/2022/demographics.htmlSubject to reporting \nirregularities\nData were available for 93.7% \nof cases reported to CDC\nChicago Mpox Cases\nIncreases in mpox \ncases detected \nhttps://www.chicago.gov/city/en/sites/monkeypox/home/data.html\nCluster of cases in Chicago\n▪From March 18 –June 12, Chicago identified 40 laboratory confirmed mpox \ncases\n–All males with a median age of 36 years (IQR 23 –49)\n–22 (55%) were vaccinated with 2 doses of JYNNEOS or 1 -dose of ACAM2000\n–5 (13%) were partially vaccinated (i.e., 1 dose JYNNEOS)\n–13 (33%) were unvaccinated\n▪11 were living with HIV\n–10 were vaccinated with 2 doses of JYNNEOS or 1 dose of ACAM2000 had \nwell controlled HIV\n▪Median time from 2nddose of JYNNEOS to mpox diagnosis was 8.4 months (IQR \n7.9–8.8 months)\nhttps://www.cdc.gov/mmwr/volumes/72/wr/mm7225a6.htm\nCluster of cases in Chicago\n▪Individuals with 2 doses of JYNNEOS or 1 dose of ACAM2000 had self -limiting \nillness\n–Lower prevalence of mucosal lesions\n–None were hospitalized\n▪Individuals with 2 doses of JYNNEOS or 1 dose of ACAM2000 had a higher \nnumber of sexual partners 3 weeks before symptom onset compared to \npartially or unvaccinated\n▪Preliminary sequencing indicates the virus is the same B.1 variant of Clade IIB \nwhich is the predominant variant of the 2022 –2023 outbreak\n–There were no mutations that would confer increased pathogenicity\n▪This investigation is ongoing, however no similar clusters are being seen \nelsewhere in the U.S.\nhttps://www.cdc.gov/mmwr/volumes/72/wr/mm7225a6.htm\nEpidemiology of Mpox in Less Affected \nPopulations\nMpox in Pregnant People in the U.S. \n▪From May 11, 2022 –May 31, 2023, 27 cases of mpox reported to CDC \noccurred in pregnant people\n▪All exposure were through close contact with a person with confirmed \ninfection (including sexual or household contact)\n▪Infections occurred in all trimesters of pregnancy\n▪11 (40.7%) received tecovirimat without adverse events reported\n▪Outcomes\n–3 (11.1%) pregnancy losses at <20 weeks \n–6 (22.2%) live births\n–18 (66.7%) pregnancies ongoing\nNeonatal Transmission and Breastfeeding \nConsiderations\n▪Of 6 live births, two neonates developed lesions within one week after \ntheir mothers became symptomatic.\n–Both neonates received oral tecovirimat; one received VIGIV.\n–Both neonates responded to treatment and were discharged home.\n–One breastfeeding neonate developed face and chest lesions 6 days \nafter the mother developed breast lesions.\n▪One woman with isolated ocular lesions continued to breastfeed her 2 -\nyear -old infant without transmission\n–Breastmilk tested on two separate occasions was MPXV PCR negative\nVIGIV: vaccinia immune globulin intravenous\nMpox in a U.S. Neonate\n▪12 hours after vaginal delivery, it was learned \nthat dad had active mpox and had contact with \nmom prior to delivery\n▪Mom developed lesions 1 day after delivery on \nthe abdomen and tested positive for mpox\n▪Baby was given VIGIV as post -exposure \nprophylaxis\n▪At 4 days old, baby developed scalp lesions and \ntested negative for HSV, positive for mpox\n▪Baby was given tecovirimat and discharged at 17 \ndays old\n▪Full resolution 4 weeks after discharge\nScalp \nlesion, \n4 days old\nScalp \nlesion, \n13days \nold\nNowalk A, Dunmore E (unpublished) VIGIV: vaccinia immune globulin intravenous\nMpox in a neonate in the United Kingdom\n•Nine days before birth, dad developed a \nfebrile illness, followed by a rash that \nresolved prior to the baby’s birth\n•Four days after birth, a similar rash \nappeared on mom\n•Nine days after birth, the infant also \ndeveloped a similar rash and diagnosed \nwith both mpox and adenovirus \n•Treated with 14 days of enteral \ntecovirimat and intravenous cidofovir\n•Critically ill, requiring 4 weeks in ICU and \n14 days on mechanical ventilation before \ndischarged home\nRamnarayan P , Mitting R, N Engl J Med . 2022 Oct 27;387(17):1618 -1620. \nEpidemiologic Characteristics of Pediatric Cases in the \nU.S., May 17 –September 24, 2022\nCharacteristic% by age group, yrs\n0–4 5–12 13–17\n(n = 16) (n = 12) (n = 55)\nSex\nMale 75% 50% 89%\nFemale 25% 50% 11%\nRace or ethnicity\nBlack, non -Hispanic 44% 42% 49%\nHispanic or Latino 31% 42% 34%\nWhite, non -Hispanic 19% 17% 9%\nAsian, non -Hispanic — — 4%\nAmerican Indian or Alaska Native, non -Hispanic — — 2%\nNative Hawaiian or other Pacific Islander, non -Hispanic 6% — —\nOther, non -Hispanic — — 2%\nExposure setting and route\nSexual contact — — 97%\nHousehold contact 93% 100% —\nOther 7% — 3%\n•<1% of U.S. cases among persons <18 years of age\n•Among adolescents, cases predominantly after male -to-male sexual \ncontact\n•Among younger children, predominantly household contact\nHennessee I. MMWR Morb Mortal Wkly Rep 2022;71:1407 –1411. \nMPXV Infections Among \nChildren Aged ≤12 Years —\nU.S., September 25 –\nDecember 31, 2022\n▪Mpox cases in children ≤12 \nyears are rare\n▪Transmission to children is \nprimarily from mpox positive \ncaregiver interactions\nNemechek K, MMWR Morb Mortal Wkly Rep 2023;72:633 –635.\nHealthcare Personnel (HCP) Infections Reported to \nCDC\n▪During investigation of cases where HCP was noted within a case report \nform, the exposure was often outside the workplace\n▪After excluding all other more likely exposures, only 23 (0.08%) cases \npotentially involved HCP exposed at work\n▪HCP infections are very rare\nHealthcare Personnel Cases That Consulted CDC (n=6)\n▪Three were sharps injuries while trying to aspirate/unroof lesions\n–CDC has since revised its recommendations to discourage unroofing \nlesions\n–Globally, this constitutes the majority of HCP infections\n▪Two cases among HCP where improper personal protective equipment was \nworn\n▪One case where the exposure route was unclear\nVaccine:  Coverage, Safety and Effectiveness\nFirst and Second Doses of JYNNEOS Vaccine \nAdministrations−United States, May, 2022 to May 2023\nOverall vaccine coverage\n1-dose: 36.7% and 2-dose: 22.7%\nRisk for recurrent mpox outbreak lasting >3 months, \nby immunity level —United States, 2023\nPollock ED . MMWR Morb Mortal Wkly Rep 2023;72:568 –573.\nCumulative Monkeypox virus infections relative to \n2022, by immunity level —United States, 2023\nPollock ED . MMWR Morb Mortal Wkly Rep 2023;72:568 –573.\nCumulative Monkeypox virus infections relative to \n2022, by immunity level —United States, 2023\nPollock ED . MMWR Morb Mortal Wkly Rep 2023;72:568 –573.>50% is needed \nto significantly \ndecrease the risk \nof large outbreaks \nJYNNEOS Vaccine Safety Monitoring \n▪CDC vaccine safety monitoring is ongoing using two surveillance systems:\n–Vaccine Adverse Event Reporting System (VAERS)\n–Vaccine Safety Datalink (VSD)\n▪V-safe data collection for mpox vaccines was available from November \n2022 through March 21, 2023\nJYNNEOS Vaccine Safety Findings Summary\n▪The adverse events most commonly reported to VAERS have been injection \nsite symptoms (redness, swelling, pain, itching)\n▪Uncommon, but expected, adverse events that have been reported to \nVAERS include:\n–Syncope:        49 reports per million doses administered\n–Anaphylaxis:  2 reports per million doses administered\n▪Myocarditis and pericarditis are adverse events of special interest\n–Observed rates are consistent with expected background rates\nJYNNEOS Vaccine Safety Conclusions\n▪VAERS and VSD data do not suggest an increased risk for myocarditis or \npericarditis following JYNNEOS, but the possibility of a small risk cannot be \nexcluded\n▪The frequencies of local and systemic reactions reported to v -safe after \nmpox vaccine were similar to those reported in clinical trials\n▪No new or unexpected safety concerns have been identified\nEpic Cosmos Study: Methods\n▪Data Source: Epic’s electronic health record (EHR) platform, Cosmos, which includes \nrecords from >173 million patients across the U.S.\n▪Design: Case -control analysis, matched 1:4 based on week of index event, HHS region, \nand gender identity\n–Cases : Patients with anmpox diagnosis or positive orthopoxvirus or MPXV laboratory \nresult from 8/15 -11/19/2022\n–Controls: Patients with an incident HIV diagnosis or HIV pre -exposure prophylaxis \n(PrEP ) prescription from 8/15 -11/19/2022\n▪Analysis:\n–Vaccine effectiveness (VE) estimated using conditional logistic regression\n–Adjusted for age, race/ethnicity, social vulnerability index, immunocompromising \nconditions\n–Stratified by route of administration and immunocompromised status\nEpic Cosmos Case -Control Study: VE for 1-Dose and 2-\nDose JYNNEOS vaccination\nhttps://www.nejm.org/doi/full/10.1056/NEJMoa2215201?query=featured_home*Adjusted for age, race/ethnicity, social vulnerability index, and immunocompromising conditions.\nCases/controls matched on week of index event, HHS region, gender identity.\nMulti -jurisdictional Case -Control Study: Methods\n▪Design: Case -control study\n▪Population: Men who have sex with men; ages 18 -49; 12 U.S. jurisdictions\n▪Methods:\n–Cases identified from jurisdictions’ probable and confirmed mpox case \nlists\n–Controls identified from healthcare settings providing HIV PrEP or \nsexually transmitted infection (STI) clinics\n–Demographics, exposure history, and vaccination history collected using \nelectronic surveys\n–Vaccination status confirmed by state immunization registries\n–Analysis: \n–VE estimated using conditional logistic regression\n–Adjusted for age, race/ethnicity, immunocompromising conditions\n–Stratified by route of administration and immunocompromised status\nMulti -jurisdictional Case -Control Study Results: VE for \n1-Dose and 2-Dose JYNNEOS vaccination\nhttps://www.cdc.gov/mmwr/volumes/72/wr/mm7220a3.htm?s_cid=mm7220a3_w\n\nMulti -jurisdictional Case -Control Study Results: VE for \n1-Dose and 2-Dose JYNNEOS vaccination\nhttps://www.cdc.gov/mmwr/volumes/72/wr/mm7220a3.htm?s_cid=mm7220a3_w\n\nNew York State Case -Control Study: Methods\n▪Design: Case -control study\n▪Data source: Linkage of case surveillance to immunization registry in New York \nState, excluding New York City\n▪Population: males at birth aged ≥18 years\n▪Methods:\n▪Cases : Adult male mpox cases during July 24 –October 31, 2022\n▪Controls : Adult male STI cases (rectal gonorrhea or primary syphilis) during July \n24 –October 31, 2022\n▪Vaccination status obtained from immunization registries\n▪Analysis: Conditional logistic regression model adjusted for week of diagnosis, \nrace, age, region within state\nNew York State Case -Control Study Results: VE for 1-\nDose and 2-Dose JYNNEOS vaccination\n*Adjusted for age, race/ethnicity, week of diagnosis, and geographic region\nhttps://www.cdc.gov/mmwr/volumes/72/wr/mm7220a4.htm\n\nVE against mpox ranges from 36% –75% for 1-Dose and\n66% –89% for 2 -Dose JYNNEOS vaccination\nVaccine effectiveness of JYNNEOS against mpox\n▪JYNNEOS vaccine is effective at reducing risk of mpox disease\n▪Protection provided by both 1 and 2 doses of JYNNEOS vaccine\n▪Highest protection provided by 2 doses, regardless of route of \nadministration\n▪Further research needed to evaluate whether immunocompromised status \nmodulates VE \n▪Further research needed to understand the duration of protection\nAcknowledgements\n▪Sarah Guagliardo\n▪Andrea McCollum\n▪Agam Rao\n▪Omoshalewa Bamkole\n▪David Yankey\n▪Rosalind Carter\n▪Romeo Galang\n▪Amanda Cohn\n▪Ian Kracalik▪Taina Joseph\n▪Anne Kimball\n▪Allie Tuttle\n▪Marie de Perio\n▪David Kuhar\n▪Jonathan Duffy\n▪Emily Faherty\n▪Ian Spicknall\n▪Chris Braden▪Varsha Neelam\n▪Andrew Nowalk\n▪Elizabeth Dunmore\n▪Shama Cash -Goldwasser\n▪Mukesh Hamal\n▪Marisa Hast\n▪Rebecca Free\n▪Jim Matthias", "summary": "National Center for Emerging and Zoonotic Infectious Diseases Updates from the 2022 –2023 U.S. Mpox Outbreak:  Epidemiology, Vaccine Safety, and Vaccine  Effectiveness ACIP Meeting June 23, 2023Faisal Syed Minhaj, PharmD, MPH, DABAT Epidemic Intelligence Service Officer Poxvirus and Rabies Branch United States Mpox Case Counts April 2022 –June 2023 https://www.cdc.gov/poxvirus/mpox/response/2022/mpx -trends.html United States Mpox Case Counts January 1 –June 6, 2023 Uptick in  cases in …", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/02-mpox-Minhaj-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 35}
{"title": "03 mpox Rao 508", "content": "National Center for Emerging and Zoonotic Infectious Diseases \nUse of JYNNEOS During Mpox Outbreaks:  Clinical \nGuidance \nAgam Rao, MD \nCAPT, US Public Health Service \nMedical Officer \nPoxvirus and Rabies Branch \nAdvisory Committee on Immunization Practices \nJune 23, 2023 \n\n \n   \n   \n   \n  \n  Vote passed during February 2023 ACIP meeting \nACIP recommends the 2 -dose* JYNNEOS vaccine series for persons \naged 18 years and older at risk of mpox during an mpox outbreak§ \n*Dose 2 administered one month after dose 1 \n§ Public health authorities determine whether there is an mpox outbreak; a single case may be considered \nan mpox outbreak at the discretion of public health authorities. Other circumstances in which a public \nhealth response may be indicated include ongoing risk of introduction of mpox into a community due to \ndisease activity in another geographic area. \n\n  \n  \n Vaccination with JYNNEOS is a 2 -dose series \n▪Post -exposure:  Concerning exposure should trigger consideration for \nvaccination regardless of where the exposure occurs (e.g., healthcare \nsetting vs. community) \n▪Pre-exposure: Whether specific populations (e.g., children, pregnant \npersons) should receive vaccinations is dependent on the risk during a \nspecific outbreak \n▪Goal of clinical guidance:  Provide general information that can inform \ndecision -making for specific mpox outbreaks \n\n \n Clinical guidance \n▪Vaccinating at -risk populations during an outbreak \n– Persons <18 years of age \n– Pregnant persons \n– Breastfeeding persons \n▪Vaccinating HCP and certain laboratorians during an outbreak \n– Healthcare personnel (HCP) \n– Certain laboratorians \n▪Administration guidance \n– Coadministration with COVID -19 vaccines \n– Immunoglobulin products \n– Other guidance \n\nVaccinating at -risk populations during an \nmpox outbreak \n \n \n \n \n \n \n \n \n Mpox in persons <18 years of age, 1970 -2022 \n▪Central and West Africa, Clades I (n= <1638*) and IIa (n= 6) \n– \n– \n– \n– \n– 1970 -1985: Increased incidence and severity in children ≤ 8 years of age \ncompared to adolescents and adults, likely because younger children had not \nbeen routinely vaccinated to prevent smallpox \n2006 -2015: No difference in incidence or severity in children compared to \nadults, likely reflecting cessation of childhood smallpox vaccinations among \npersons who were adults at the time of evaluations \n▪United States and United Kingdom, Clades IIa (n= 12) and IIb (n= 125) \n2 children hospitalized during 2003 U.S. outbreak and 1 child hospitalized during \n2021 in United Kingdom; all recovered \nNo severe manifestations among U.S. children during current outbreak \nSevere manifestation reported among a neonate in UK (adenovirus co -infection) \n*Includes 18 –19-year -olds from the Democratic Republic of the Congo \n\nUse of JYNNEOS in persons aged <18 years \n▪\n▪\n▪12-17 years of age, n=349 \n• No safety signals identified via CDC surveillance  systems \n• No efficacy data from pre-licensure trials \n• Unable to  evaluate real-world VE during current outbreak  \n U.S. JYNNEOS first doses§ \nadministered to pediatric patients by \nage and gender \n \n  \ngirl \nboy \n• NIH  clinical trial underway to evaluate safety and efficacy \n0-11 years of age, n=377 \n• No safety signals identified via CDC surveillance  systems \n• No efficacy data from pre-licensure trials \n• Unable to evaluate real-world VE during current outbreak\n• Concerns that dose may be different for those in the \nyounger ages \n• No clinical trials or other studies planned at this time \nData from recent publication* is encouraging § Fewer children  received  2 doses (compared  \nto 1  dose);  CDC unpublished  data (does not \ninclude data from one state) \n* Ladhani et  al. Lancet In  fect  Dis. 20 23 \n\n \n  \n \n \n  \n Clinical guidance for children and adolescents \n▪For persons 6 months -17 years, JYNNEOS should be administered as PrEP or PEP  \n(as indicated by public health authorities for a specific outbreak) if a high -risk \nexposure has occurred \n– \n– \n– For younger children (e.g., <6 years of age), clinicians should be aware that no studies involving \nJYNNEOS have been performed to determine appropriate dose \nDecisions about vaccination with JYNNEOS should involve risk/benefit assessment for every \npediatric age group during a specific outbreak \nAfter completion of ongoing clinical trial, ACIP may consider a vote re: use of JYNNEOS in \nchildren 12 -17 years of age during mpox outbreaks \n▪For children < 6 months of age, VIGIV should be administered in lieu of JYNNEOS if \nPEP is indicated \n\n              \n                      \n    \n Detection and transmission of MPXV during the \ncurrent outbreak \n* DNA has been detected at Ct values <35 in recovered patients more than 30 days after illness onset in an upper respiratory tract swab, saliva, and semen. \n† The preponderance of existing data support exposure to anorectal and vulvovaginal tissues and fluids as capable of transmit ting infection; however, it is difficult with current evidence to definitively isolate these exposures \nfrom other concomitant exposures (see text). \n‡ Includes body modification with piercings and tattooing. \nhttps://www.cdc.gov/poxvirus/monkeypox/about/science -behind -transmission.html \n\n \n \n \n  \n Mpox in pregnant persons \n▪Historically* \n– \n– \n– \n– Mpox known to have been transmitted pre and perinatally to at least 2 \nneonates \nNeonatal outcomes among neonates born to mothers who had mpox \n(n=5) included a stillbirth, self -limited rash, and healthy neonates \n▪During 2022/2023 U.S. outbreak \nOutcomes among pregnant women are being evaluated \nTransmission to neonate known to have occurred \n*This information is limited to published reports \nfrom countries where MPXV is endemic \n\n \n \n Use of JYNNEOS in pregnant persons \n▪Unknown if JYNNEOS administered to pregnant persons during 2022/2023 \noutbreak \n▪No adverse events (passively reported via VAERS) have been received \n▪2022 ACIP recommendations for persons at risk for occupational exposure \nexplicitly states JYNNEOS not contraindicated in pregnant persons \n\n \n   \n \n Mpox spread during breastfeeding and use of \nJYNNEOS among breastfeeding persons* \n▪Mpox known to be transmitted when child exposed to mpox skin lesions \n(e.g., under breast) \n▪Mpox not known to be transmitted via breast milk; for one patient during \n2022 outbreak, breast milk samples negative for MPXV DNA by PCR \n▪No information about whether breast -feeding persons received JYNNEOS \nduring ongoing outbreak; however, no VAERS reports were received that \nmentioned breast -feeding persons \n*https://www.cdc.gov/mmwr/volumes/72/wr/mm7201a2.htm?s_cid=mm7201a2_w \n\n \n \n \n \n \n \n \n Proposed clinical guidance for pregnant and breastfeeding persons \n▪JYNNEOS not contraindicated in persons who are pregnant or breastfeeding \n▪Available human data insufficient to determine vaccine -associated risks in \npregnancy.  However, animal models including rats and rabbits have shown no \nevidence of harm to developing fetus \n▪Safety and efficacy of JYNNEOS not been evaluated in breastfeeding women.  It is \nnot definitively known whether JYNNEOS is excreted in human milk. Data are not \navailable to assess the impact of JYNNEOS on milk production or the safety of \nJYNNEOS in breastfed infants. However, because JYNNEOS vaccine is replication -\ndeficient, it likely does not present a risk of transmission to breastfed infants and \ncan be administered to women who are breastfeeding after weighing the benefits \nand harms \n▪If high -risk exposures cannot be avoided or have already occurred, persons who are \npregnant or breastfeeding may receive JYNNEOS \n\nVaccinating HCP and certain laboratorians \nduring an mpox outbreak \n \n \n \n \n \n  Mpox acquired via laboratory or healthcare exposures \n▪2022/2023 U.S. mpox outbreak \n– Laboratory personnel: No reports \n– HCP: 23 potential exposures \n• Most associated with sharps injuries while attempting to unroof, open, or \naspirate mpox lesions* \n• Some associated with suboptimal PPE use \n▪Historical data from endemic countries \n– Laboratory personnel:  No data \n– HCP:  Acquired providing care to family members/friends in homes or with \nlittle PPE \n*Unroofing or aspirating lesions is discouraged https://www.cdc.gov/poxvirus/mpox/clinicians/prep -\ncollection -specimens.html \n\n              \n                      \n    \n Detection and transmission of MPXV during the \ncurrent outbreak \n* DNA has been detected at Ct values <35 in recovered patients more than 30 days after illness onset in an upper respiratory tract swab, saliva, and semen. \n† The preponderance of existing data support exposure to anorectal and vulvovaginal tissues and fluids as capable of transmit ting infection; however, it is difficult with current evidence to definitively isolate these exposures \nfrom other concomitant exposures (see text). \n‡ Includes body modification with piercings and tattooing. \nhttps://www.cdc.gov/poxvirus/monkeypox/about/science -behind -transmission.html \n\n \n  \n      \n    \n    \n         \n  Use of JYNNEOS for preexposure vaccination of persons at risk for \noccupational exposure to orthopoxviruses :  Recommendations of the \nACIP—United States, 2022 \n▪For research laboratory personnel* and clinical laboratory personnel \nperforming diagnostic testing for orthopoxviruses§, ACIP recommends use \nof JYNNEOS for primary vaccination as an alternative to ACAM2000 \n▪For healthcare personnel who administer ACAM2000 or care for patients \ninfected with orthopoxviruses , ACIP recommends use of JYNNEOS (as an \nalternative to ACAM2000) based on shared clinical decision -making \n*Research laboratory personnel are those who directly handle cultures or animals contaminated or infected with replication -compe tent vaccinia virus, \nrecombinant vaccinia viruses derived from replication -competent vaccinia strains (i.e., those that are capable of causing clinic al infection and producing \ninfectious virus in humans), or other orthopoxviruses that infect humans (e.g., Monkeypox virus, Cowpox virus, and Variola virus) \n§Clinical laboratory personnel who perform routine chemistry, hematology, and urinalysis testing, including for patients with suspected or confirmed \northopoxvirus infections, are not included in this recommendation because their risk for exposure is low \n\n \n \n      \n     \n          \n         \n       Pre-exposure prophylaxis:  Use of JYNNEOS during \nmpox outbreaks \n▪For research laboratory personnel* and clinical laboratory personnel performing \ndiagnostic testing for mpox§, ACIP recommends use of JYNNEOS for pre-exposure \nvaccination as an alternative to ACAM2000 \n▪For clinical laboratory personnel who handle specimens that may have a higher \npossibility of containing replication competent MPXV (e.g., lesion material, throat \nswabs, oral swabs, rectal swabs), and certain healthcare personnel who care for \npatients infected with mpox or administer ACAM2000 §, ACIP recommends use of \nJYNNEOS (as an alternative to ACAM2000) based on shared clinical decision -making \n*Research laboratory personnel are those who directly handle cultures or animals contaminated or infected with monkeypox viru s (MPXV) \n§Vaccination is not routinely recommended for clinical laboratory personnel who perform routine chemistry, hematology, and urinalysis testing, \nincluding for patients with suspected or confirmed MPXV infection , healthcare personnel who care for patients with mpox or administer ACAM2000. \nRecommended infection prevention and control practices are effective in minimizing transmission. Vaccination can be offered b ased on site -and \nactivity -specific biosafety risk assessments (e.g., identification of laboratory procedures with a high likelihood of generatin g aerosols or inadequate PPE \navailability) \n\n Administration guidance \n \n \n  \n Coadministration of JYNNEOS with COVID -19 vaccines \n▪There is no required minimum interval between receiving any COVID -19 vaccine \nand JYNNEOS vaccine (e.g., for mpox prevention), regardless of which vaccine is \nadministered first \n▪People, particularly adolescent and young adult males, who are recommended to \nreceive both vaccines might consider waiting 4 weeks between vaccines. This is \nbecause of the observed risk for myocarditis and pericarditis after receipt of \nACAM2000 orthopoxvirus vaccine and COVID -19 vaccines and the hypothetical risk \nfor myocarditis and pericarditis after JYNNEOS vaccine. However, if a patient’s risk \nfor mpox or severe disease due to COVID -19 is increased, administration of \nJYNNEOS and COVID -19 vaccines should not be delayed \n\n \n  \n  Implications of JYNNEOS administration in close \ntemporal proximity to immunoglobulin products \n▪Antibodies to measles and varicella high in immune globulin products; \nadministration of these in close temporal proximity can prevent the \nvaccine from entering cells and being effective \n▪Antibodies to orthopoxviruses are believed to be low in most immune \nglobulin products (e.g., IVIG) and will likely remain low in the future \n▪Antibodies to orthopoxviruses are present in VIGIV (purified \nimmunoglobulin from persons vaccinated against smallpox); however, \nwhether these could prevent the vaccine from being effective is unknown \n\n \n \n \n  \n  Clinical guidance when JYNNEOS and immunoglobulin \nproducts are temporally administered \n▪Most immunoglobulin products: No precautions are necessary if JYNNEOS \nis administered in close temporal proximity to IVIG \n▪VIGIV \n– VIGIV could interfere with immune response to JYNNEOS \n• Ideally, administration of JYNNEOS should be delayed if VIGIV was recently administered \n• The duration for which it should be delayed is unknown; during outbreaks, it is acceptable \nto administer a dose of JYNNEOS; however, public health consultation should be obtained \nfor case specific guidance about an additional dose at a later time \n– Unlikely that VIGIV would be administered in close proximity to JYNNEOS \n\n \n \n \n  \n \n Other administration guidance \n▪Unintentional delays do not require restarting the series; the second dose \nshould be administered as soon as possible even if >1 year has elapsed \n▪In settings where subcutaneous administration is not preferred (e.g., \nvaccine is in short supply), the vaccine can be administered intradermally \n▪In settings where intradermal administration is not possible (e.g., because \nstaff are not trained or uncomfortable) \n– Jurisdictions may administer subcutaneous vaccinations and prioritize first doses of the 2 -dose \nJYNNEOS series \n– Second doses should be administered as soon as vaccine availability allows \n▪Decisions about vaccine administration should ensure equitable \ndistribution of vaccine doses \n\n  \n Acknowledgements \n▪Faisal Minhaj ▪Amanda Cohn \n▪Jim Campbell ▪Melinda Wharton \n▪Jafar Razeq ▪Manisha (Mo) Patel \n▪Mark Russi ▪Paul Rota \n▪Howard Minkoff ▪Rosalind Carter \n▪Sathesh Panayampalli ▪Catherine McLean \n▪Christina Hutson ▪Jonathan Duffy \n▪David Kuhar ▪Ian Kracalik \n▪Marie de Perio ▪Leora Feldstein \n▪John Brooks ▪Andrea McCollum ▪ACIP Mpox WG \n▪Sara Oliver \n▪Tara Anderson \n▪Evelyn Twentyman \n▪Allie Tuttle \n▪AAP’s COID and \nRedbook \n\n \n   \n   \n  \n \n   Questions? \nFor more information, contact CDC \n1-800-CDC-INFO (232 -4636) \nTTY: 1 -888-232-6348  www.cdc.gov \nThe findings and conclusions in this report are those of the authors and do not necessarily represent the \nofficial position of the Centers for Disease Control and Prevention. \nNational Center for Emerging and Zoonotic Infectious Diseases \nDivision of High -Consequence Pathogens and Pathology", "summary": "National Center for Emerging and Zoonotic Infectious Diseases  Use of JYNNEOS During Mpox Outbreaks:  Clinical  Guidance  Agam Rao, MD  CAPT, US Public Health Service  Medical Officer  Poxvirus and Rabies Branch  Advisory Committee on Immunization Practices  June 23, 2023                      Vote passed during February 2023 ACIP meeting  ACIP recommends the 2 -dose* JYNNEOS vaccine series for persons  aged 18 years and older at risk of mpox during an mpox outbreak§  *Dose 2 administered one…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/03-mpox-Rao-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 25}
{"title": "04 mpox Rao 508", "content": "National Center for Emerging and Zoonotic Infectious Diseases\nConsiderations for long -term protection against mpox\nAdvisory Committee on Immunization Practices\nJune 23, 2023Agam Rao, MD\nCAPT, US Public Health Service\nMedical Officer\nPoxvirus and Rabies Branch\nCDC collaborative studies examining serologic \nresponse to JYNNEOS vaccinations\nStudy Goals Timepoints/Duration Participant Information\n•DRC\n•Healthcare personnel\n•Democratic Republic of the \nCongo, Tshuapa Province•Safety\n•Immunogenicity\n•Effectiveness•2-year studies\n•Serum obtained on days 0, \n14, 28, and 42, and 6, 12, \n18, 24 months\n•Booster: 5 years\n•Serum obtained on days 0, \n7, 14•1000 participants SC/SC liquid \nformulation\n•600 participants SC/SC lyophilized \nformulation\n•~170 participants (Booster)\n•DC PEP++ \n•Expanded post -exposure \nprophylaxis in MSM with \nbehaviors that increase risk \nfor mpox\n•DC Health\n•Washington, DC•Immunogenicity\n•Comparison between \ndifferent routes of \nvaccination•2-year study\n•Days 0, 28, and 42 -56 and 6 \nmonths\n•12, 18, and 24 months \nplanned. •330 participants\n•Participants with 2 timepoints (n=216), \n3 timepoints (n=70), or all 4 timepoints \n(n=66)\nCDC studies examining serologic response to JYNNEOS \nvaccinations\nStudy Goals Timepoints/Duration Participant Information\n•DRC\n•Healthcare personnel \nDemocratic Republic of the \nCongo, Tshuapa Province•Safety\n•Immunogenicity\n•Effectiveness•2-year studies\n•Serum obtained on days 0, \n14, 28, and 42, and 6, 12, \n18, 24 months\n•Booster dose: 5 years\n•Serum obtained on days 0, \n7, 14•1000 participants SC/SC liquid \nformulation\n•600 participants SC/SC lyophilized \nformulation\n•~170 participants (Booster)\n•DC PEP++ \n•Expanded post -exposure \nprophylaxis in MSM with \nbehaviors that increase risk \nfor mpox\n•DC Health\n•Washington, DC•Immunogenicity\n•Comparison between \ndifferent routes of \nvaccination•2-year study\n•Days 0, 28, and 42 -56 and 6 \nmonths\n•12, 18, and 24 months \nplanned. •330 participants\n•Participants with 2 timepoints (n=216), \n3 timepoints (n=70), or all 4 timepoints \n(n=66)\n\nCDC studies examining serologic response to JYNNEOS \nvaccinations\nStudy Goals Timepoints/Duration Participant Information\n•DRC\n•Healthcare personnel \nDemocratic Republic of the \nCongo, Tshuapa Province•Safety\n•Immunogenicity\n•Effectiveness•2-year studies\n•Serum obtained on days 0, \n14, 28, and 42, and 6, 12, \n18, 24 months\n•Booster dose: 5 years\n•Serum obtained on days 0, \n7, 14•1000 participants SC/SC liquid \nformulation\n•600 participants SC/SC lyophilized \nformulation\n•~170 participants (Booster)\n•DC PEP++ \n•Expanded post -exposure \nprophylaxis in MSM with \nbehaviors that increase risk \nfor mpox\n•DC Health\n•Washington, DC•Immunogenicity\n•Comparison between \ndifferent routes of \nvaccination•2-year study\n•Days 0, 28, and 42 -56 and 6 \nmonths\n•12, 18, and 24 months \nplanned. •330 participants\n•Participants with 2 timepoints (n=216), \n3 timepoints (n=70), or all 4 timepoints \n(n=66)\nCDC studies examining serologic response to JYNNEOS \nvaccinations\nStudy Goals Timepoints/Duration Participant Information\n•DRC\n•Healthcare personnel \nDemocratic Republic of the \nCongo, Tshuapa Province•Safety\n•Immunogenicity\n•Effectiveness•2-year studies\n•Serum obtained on days 0, \n14, 28, and 42, and 6, 12, \n18, 24 months\n•Booster dose: 5 years\n•Serum obtained on days 0, \n7, 14•1000 participants SC/SC liquid \nformulation\n•600 participants SC/SC lyophilized \nformulation\n•~170 participants (Booster)\n•DC PEP++ \n•Expanded post -exposure \nprophylaxis in MSM with \nbehaviors that increase risk \nfor mpox\n•DC Health\n•Washington, DC•Immunogenicity\n•Comparison between \ndifferent routes of \nvaccination•2-year study\n•Days 0, 28, and 42 -56 and 6 \nmonths\n•12, 18, and 24 months \nplanned. •330 participants\n•Participants with 2 timepoints (n=216), \n3 timepoints (n=70), or all 4 timepoints \n(n=66)\nDRC study:  Detection of IgG antibody after JYNNEOS \nvaccination\n▪ Serum specimens tested for \npresence of orthopoxvirus -specific \nIgG antibody using an enzyme -\nlinked immunosorbent assay (ELISA)\n▪ Positivity determined by Optical \nDensity (OD) –cutoff value (COV)\n▪ Circulating IgG levels peaked slower \nand lower in persons who received \nno previous orthopoxvirus vaccine\n▪ Circulating IgG levels stayed higher \nfor a longer period of time in \npersons previously vaccinated\nNo previous orthopoxvirus\nvaccinationPrior Vaccination*\nDays from JYNNEOS dose 1\n\n2022 ACIP recommendations for persons at \noccupational risk for orthopoxvirus exposures\n▪Reviewed data indicated an anamnestic response occurs 2 years after the \n2-dose series\n▪ACIP recommendations:  persons (typically laboratorians) at occupational \nrisk for variola virus and MPXV exposures should receive JYNNEOS booster \ndoses every 2 years\n▪No data to indicate whether anamnestic response would occur >2 years \nafter 2 -dose series; standard -of-care for these persons working with \nresearch grade virus has been booster doses\nWG’s interpretation\n•Significance of waning circulating antibody levels is unknown\n•Anamnestic response elicited 2 years after JYNNEOS primary series\n•2022 ACIP recommendations were for exposures that are different from \nthose experienced during the current outbreak\nReal -world data during 2022/2023 U.S. mpox outbreak\n▪VE studies\n–3 studies: NY State, Epic Cosmos, and Multijurisdictional Case -Control Studies\n–VE ranged from 36% –75% for 1 dose and 66% –89% for 2 doses\n▪Mpox cases among persons who received 2 doses have occurred:  Some \ncases expected; reported as early as August 2022\n▪2023 Chicago cluster involving persons who received 2 JYNNEOS doses*\n–No U.S. clusters of a similar size reported\n–No hospitalizations; opiates not typically prescribed for pain control\n–Sequences typical of B.1 variant of MPXV Clade IIb; no mutations that would \nconfer increased pathogenicity\n*For most, at least one dose (and often both doses) were administered \nsubcutaneously\nWG’s interpretation\nThird dose currently not indicated for entire population eligible for vaccination\nAdditional vaccine doses for \nimmunocompromised persons, including \npersons with HIV\nSafety of third dose of JYNNEOS\nMinhaj et al, unpublished data, 2023020406080100\nAny Reaction Pain Edema Pruritis Induration Erythema Tenderness OtherPercentDose 1 Dose 2 Dose 3Select vaccine -associated adverse events, by dose, healthcare personnel in \nDemocratic Republic of Congo (n=706 for first and second doses and n=170 for 3rd\ndose)Limitation\n▪Study population may not be \nrepresentative of U.S. populationCurrent Knowledge\nCDC’s DRC study: Study of HCP shows \nincreased adverse events among \nrecipients of 3rddose at 5 years after \nprimary series\nSafety of third dose of JYNNEOS in persons with HIV\nOverton 2020 VaccineLimitation\nSmall numbers of total subjects; \nonly 30 patients received third \ndose; difficult to know likelihood of \nincreased adverse eventsCurrent Knowledge\nStudy of persons with HIV (CD4 100 –\n500) shows increased adverse events \n(albeit not significant) among \nrecipients of third dose at week 12\n020406080100\nAny AE Grade 3 AE Site Pain Pruritis Induration Myalgia FatiguePercent2 doses, standard volume 2 doses, double volume 3 doses, standard volumeSelect vaccine -associated adverse events, by dose, among persons with HIV in the United States (n=87 for 1stand \n2nddoses, n= 30 for third dose)\nWG’s interpretation\nThird dose might result in more adverse events; this could deter some persons \nfrom receiving first and second doses\nSerologic Response to JYNNEOS among persons with HIV\nCurrent Knowledge\n▪For nearly 600 persons with CD4 \n>200*, serologic response to 2 -dose \nseries equivalent to response in \npersons without HIV\n* measured in cells/mm3Limitation\n▪No assessment of serologic \nresponse for persons with CD4 \n<100\nGreenberg 2013 J Infect Dis ; Overton 2015 Open Forum Infect Dis ;\n\nSerologic Response to JYNNEOS among persons with HIV\nCurrent Knowledge\n▪For persons with CD4 100 -500* \nand lifetime nadir <200*, serologic \nresponse of 3 doses is similar to 2 \ndoses\n▪Review of unpublished data:  No \ncorrelation between low CD4 count \nand antibodies after vaccine\n* measured in cells/mm3Limitation\n▪Serologic correlate of protective \nimmunity unknown\n▪Small number of subjects: only \n26 subjects in 3 -dose arm\nOverton 2020 Vaccine\n\nCases Controls Adjusted †VE (95% CI)\nPartial vaccination VE, \nimmunocompromised22 52 51.0% ( -27.6 –81.2)\nFull vaccination VE, \nimmunocompromised9 31 70.2% ( -37.9 –93.6)VE of JYNNEOS in persons with self -reported \nimmunocompromise (including HIV)\nCurrent Knowledge\nVE point estimates for persons who are \nimmunocompromised* lower than for \ngeneral population of vaccinated \npersons for both 1 and 2 dosesLimitation\n▪Estimates do not differ statistically \nfrom estimates for general \npopulation \n▪Few persons for whom this was \nevaluated; Confidence Intervals wide\nhttps://www. cdc.gov/mmwr/volumes/72/wr/mm7220a3.htm?s_cid=mm7220a3_w* predominately HIV (CD4 cell count not specified)\nVaccine Effectiveness (%)\n†Adjusted for age, race/ethnicity, immunocompromised status, reported close contact with a \nconfirmed/suspected mpox case in 3 weeks prior to index event, and month of index event\nSeverity of infections among fully vaccinated: National \nreporting and anecdotal reports\nLimitation\n▪Data e xtrapolated from surveillance \nand consultation data ; no formal \nreview of electronic health records \nlinked to vaccine registries\n▪Not known whether persons who do \nnot respond to 2 doses of JYNNEOS \nwould respond to a third doseCurrent Knowledge\n▪>10,000 mpox cases among persons with \nHIV; however n o confirmed reports of \nsevere mpox illness after full vaccination\n▪CDC reviewed data reported from health \ndepartments for fully vaccinated persons \nwith mpox and confirmed none were \nhospitalized due to severe manifestations \nof mpox\n▪Anecdotally, CDC told there was a severe \ncase in a patient who was not fully \nvaccinated; however, details not known\nWG’s interpretation\nThere is no convincing data to indicate patients with moderate -severe \nimmunocompromise would benefit from an additional dose of JYNNEOS\nFirst and Second Doses of JYNNEOS Vaccine \nAdministrations−United States, May, 2022 to May 2023\nOverall vaccine coverage\n1-dose: 36.7% and 2-dose: 22.7%\nConclusions\n▪WG prefers no CDC recommendation for third JYNNEOS dose at this time, \nincluding for persons with advanced HIV or other severe \nimmunocompromise\n▪WG emphasized several strategies\n–Encourage 2 -dose vaccinations among persons who do not have immunity*\n–Prevent or minimize life -threatening manifestations \n•Optimizing immune function (e.g., with HIV antiretrovirals), ideally before mpox exposure\n•Using CDC interim treatment considerations§to manage patients with (or at risk of) \nsevere manifestations of mpox\n*e.g., persons who have not had mpox\n§Rao et al. 2023. MMWR\nNext steps\n▪Continue to collect and evaluate any existing data, particularly about use of \nJYNNEOS in immunocompromised persons\n▪Attempt to characterize severity of mpox cases experienced by people who \nreceived 2 JYNNEOS doses\n▪Continue ongoing VE studies\n▪Update CDC interim clinical considerations* if additional JYNNEOS vaccine \ndoses are recommended\nAcknowledgements\n▪ACIP mpox WG\n▪John Brooks\n▪Rosalind Carter\n▪Chris Braden\n▪Christy Hutson\n▪Sathesh Panayampalli\n▪Michael Townsend\n▪Shireesha Dhanireddy\n▪Inger Damon\n▪Faisal Minhaj▪Erin Whitehouse\n▪Allie Tuttle\n▪Sarah Guagliardo\n▪William Bower\n▪Andrea McCollum\n▪Emily Faherty\n▪Willie Bower\n▪Christy Hughes\n▪Bavarian Nordic \nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the \nofficial position of the Centers for Disease Control and Prevention.\nNational Center for Emerging and Zoonotic Infectious Diseases\nDivision of High -Consequence Pathogens and PathologyQuestions and Comments?", "summary": "National Center for Emerging and Zoonotic Infectious Diseases Considerations for long -term protection against mpox Advisory Committee on Immunization Practices June 23, 2023Agam Rao, MD CAPT, US Public Health Service Medical Officer Poxvirus and Rabies Branch CDC collaborative studies examining serologic  response to JYNNEOS vaccinations Study Goals Timepoints/Duration Participant Information •DRC •Healthcare personnel •Democratic Republic of the  Congo, Tshuapa Province•Safety…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/04-mpox-Rao-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 24}
{"title": "01 Mening Poehling 508", "content": "National Center for Immunization & Respiratory Diseases\nACIP Meningococcal Vaccines Work Group \nIntroduction\nKatherine Poehling, MD, MPH\nWork Group Chair\nJune 23, 2023\n\n2Meningococcal Vaccines Work Group\n▪ ACIP Members on the WG\n–Kathy Poehling (Chair)\n–Lynn Bahta\n–Jamie Loehr\n▪ Ex Officio WG Members\n–Margaret Bash (FDA)\n–Mark Connelly (FDA)\n–Francisco Leyva (NIH)\n▪ WG Liaisons and Consultants\n–Amra Resic (AAFP)\n–Samir Shah (AAP) \n–Sharon McMullen (ACHA)\n–Cacky Tate (AIM)\n–Paul Cieslak (CSTE)\n–Kathy Hsu (IDSA)\n–Joseline Zafack (NACI)\n–Jeff Goad (NFID)\n–Jessica Cataldi (PIDS)\n–Amy Middleman (SAHM)\n–David Stephens (Emory)▪ CDC Contributors\n–Jenn Collins (DBD/NCIRD)\n–Lucy McNamara (DBD/NCIRD)\n–LeAnne Fox (DBD/NCIRD)\n–Susan Hariri (DBD/NCIRD)\n–Amy Rubis (DBD/NCIRD)\n–Noele Nelson (DBD/NCIRD)\n–Alison Albert (DBD/NCIRD)\n–Angela Jiles (DBD/NCIRD)\n–Jonathan Duffy (DHQP/NCEZID)\n–Tanya Myers (DHQP/NCEZID) \n–Ismael Ortega -Sanchez (DVD/NCIRD)\n–Liz Velazquez (ISD/NCIRD)\n–Jessica MacNeil (ACIP Secretariat)\n▪ GRADE/EtR Support\n–Doug Campos -Outcalt (Arizona)\n–Rebecca Morgan (Case Western Reserve)\n3February ACIP Meeting Recap\n▪\n▪\n▪Epidemiology of meningococcal disease in the United States\nPfizer’s MenABCWY vaccine clinical trials data\nWork Group interpretation of Pfizer’s MenABCWY trials data\n4Summary of Recent Work Group Activities Involving Pfizer Vaccine\n▪\n▪Pfizer and CDC staff presented their cost effectiveness models for Pfizer’s \npentavalent vaccine\nWork group members reviewed GRADE and EtR findings for Pfizer’s vaccine \nand deliberated about what to propose to ACIP\n5Agenda for Today\n▪\n–\n▪\n–CDC’s cost effectiveness model\nDr. Ismael Ortega -Sanchez, CDC\nWork group’s GRADE/EtR assessment results\nDr. Sam Crowe, CDC", "summary": "National Center for Immunization & Respiratory Diseases ACIP Meningococcal Vaccines Work Group  Introduction Katherine Poehling, MD, MPH Work Group Chair June 23, 2023  2Meningococcal Vaccines Work Group ▪ ACIP Members on the WG –Kathy Poehling (Chair) –Lynn Bahta –Jamie Loehr ▪ Ex Officio WG Members –Margaret Bash (FDA) –Mark Connelly (FDA) –Francisco Leyva (NIH) ▪ WG Liaisons and Consultants –Amra Resic (AAFP) –Samir Shah (AAP)  –Sharon McMullen (ACHA) –Cacky Tate (AIM) –Paul Cieslak (CSTE)…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/01-Mening-Poehling-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 5}
{"title": "02 Mening Ortega Sanchez 508", "content": "The Cost -effectiveness of a Potential Pentavalent \nMeningococcal Conjugate Vaccine (Men ABCWY) \nversus the Current Men ACWY and Men B \nvaccines for US Adolescents \nIsmael R. Ortega -Sanchez, PhD\nCDC/NCIRD\nACIP meeting, June 23, 2023\nDisclaimer : The findings and conclusions in this report are those of the authors and do not necessarily \nrepresent the views of the Centers for Disease Control and Prevention. 1\n\n2Conflict of Interest\nCDC/NCIRD collaborators:  All collaborators, No conflict of interest\n•Ismael R Ortega -Sanchez \n•Samuel James Crowe\n•Lucy Alexandra McNamara\nAcknowledgements\n•Members of the Meningococcal ACIP working group\n•Also, for review and comments provided by the economic team at ISD/NCIRD\n\nOverview\n•Policy question: Should the pentavalent vaccine (Men ABCWY) be \nconsidered as an option for Men ACWY/Men B vaccination in people \ncurrently recommended to receive both vaccines?​\n3Current vaccination Potential vaccination strategies\nFirst dose Second dose First dose Second dose Third dose Key Label\nAt 11 -12 yrsold\nwith MenACWYAt 16 yrsold\nwith MenACWYAt 11 -12 yrsold with \nMenACWYAt 16 yrsold with\nMenABCWYAt 16 yrsold with \nMenBQ-P-B\nAt 11 -12 yrsold with \nMenABCWYAt 16 yrsold with \nMenABCWYNone (N) P-P-N\nAt 16 yrs old \nwith Men BAt 16 yrsold \nwith Men BAt 11 -12 yrsold with \nMenACWYAt 16 yrsold with\nMenABCWYAt 16 yrsold with\nMenABCWYQ-P-P\nAt 11 -12 yrsold with \nMenABCWYAt 16 yrsold with\nMenABCWYAt 16 yrsold with\nMenABCWYP-P-P\nMen ABCWY = Potential pentavalent vaccine (P) with serogroups A, B, C W Y \nMen ACWY = currently recommended quadrivalent vaccine ( Q) for serogroups A, C, W, Y, \nMen B =currently recommended monovalent vaccine for serogroup B\nEconomic analysis\nQuestion : Is vaccinating adolescents 11 -16 years old with Pentavalent vaccine \nseries to prevent Invasive Meningococcal Disease in adolescents cost-effective ?\nComparator Interventions\nBase -case scenario: What is the Incremental cost -effectiveness of vaccinating \nhealthy adolescents 11 -12 and 16 years old with Pentavalent vaccine relative to \nusing Men ACWY and Men B vaccines ?\n4MenACWY vaccine: one \ndose at 11 -12 years and \none dose at 16 years. \n(Q-Q)\nMenB vaccines: two \ndoses at 16 years. \n(B-B)Use of Pentavalent \nMenABCWY vaccine \ncombined e ither as\nQ-P-B\nP-P-N\nQ-P-P\nor P-P-P\nMethods: Study question\nObjectives :\n•Toanalyze theimpact ofeach meningococcal vaccination strategy fortheprevention ofInvasive\nMeningococcal Disease -related medical care, long-term sequalae and deaths among US\nadolescents .\n•Tocompare thehealth and cost impact associated with theuse ofpentavalent meningococcal\nvaccine vs.current quadrivalent Men ACWY andMen Bmeningococcal vaccines, toestimate cost-\neffectiveness interms ofhealth -related quality oflife,based oncurrently available data.\nPerspective\n•Base case ispresented from asocietal perspective, including\n•Quality -of-lifeimpact tocases andindirect costs intheform ofproductivity lossandlifetime lost\nearnings duetoaIMD-related acute disease, long-term sequelae ordeath .\n5\nMethods: Time frame and analytic horizon\nTime frame and analytic horizon: \n•Intervention time frame: cohort of 11yrs followed until 25yrs of age \n•Meningococcal serogroup specific cases annually for 15 years\n•Long term sequelae and death for 15 years\n•Analytic horizon: \n•Outcomes counted annually or cumulative for 15 year\n•IMD disease long -term sequelae complications counted annually or cumulative for 15 years\n•Lifetime medical and indirect cost of disabilities and deaths \nDiscounting:\n•3% annual discount rate applied to cost and health outcomes .\n6\nMethods: the model\nStatic decision analytic model \n•Able to track 11 -year-olds cohort yearly \nwith states that transition from \nsusceptibility, infected IMD, recovered \nor death\n•Monte Carlo simulations for uncertainty \nand probabilistic sensitivity analyses  \n•Allowing pairwise incremental \ncomparison of hypothetical strategies \nversus the standard of care \n•Aggregating the associated IMD health \noutcomes and costs \n•With specific vaccination program \neffectiveness, safety and costs\n•For a cohort of 11 -year-olds followed for \n15 years 7\nrecoveredvaccinated\nInvasive Meningococcal \nDiseaseNon-invasive \nDisease\n8Prevention of:\n•IMD cases\n•Associated sequelae\n•Associated deaths\nQALYs saved\n$/Life year saved\n$/QALY saved\nNNV avert a: \n•IMD case\n•Complication\n•DeathEpidemiologic \nData\nVaccine\nCharacteristics\nAcute and\nLong -term \nCost Data\nIndirect \nCost\nDataQuality\nOf\nLife\nDataOther \nParameters\nCohort \nModelMethods: Inputs and main outcomes\n9Epidemiologic Data\n•Age-year -and B+C+Y+W serogroup -specific pre -vaccine and vaccine era \nincidence rates \n•1996 -2005 (pre -vaccine) and 2006 -2020 (“vaccine era” for serogroups CWY) \n•1994 -2013 (pre -vaccine) and 2017 -2020 (“vaccine era” for serogroup B)\n•Age-and serogroup -specific case fatality ratios \n•Proportion of survivors with sequelae by condition\n10Changes in the Average Annual Incidence in Vaccine Serogroups \nBCYW by Age per 100,000\nSource: Data from ABC Core Surveillance and NNDSS\nNote: Trend and variability across years are used for range of uncertainties and sensitivity analyses •Rates of IMD disease \nremain relatively \nhigher in late \nadolescence, but in \ngeneral rates have \nbeen declining for all \nage groups.\n•Overall, IMD \nincidence rates are \none sixth of those \nfrom recent pre -\nvaccine era \n0.000.200.400.600.801.001.201.401.60\n=<10 11 12 13 14 15 16 17 18 19 20 21 22 >=23IMD incidence per 100,000\nAgeCWY & B PreVaxs\nCWY & B  VaxsEra\n11Background mortality and IMD Case Fatality Ratios by Age Group and \nSerogroups CYW ,  Serogroup B and Serogroups BCWY *\n*CFR data is from NNDSS for 2008 -202000.050.10.150.20.25\n0-4m 5-11m 1yr 2- 4yrs 5-10yrs 11-17yrs 18-22yrs 23-32yrs 33-64yrs >=65yrsCase fatality rate of IMD\nAge group B\nC Y W\nB C Y WAge (years) US mortality rates \n(per 100,000)\n11 12.5\n12 14.8\n13 18.6\n14 24.2\n15 32.2\n16 43.0\n17 56.4\n18 71.7\n19 84.4\n20 94.1\n21 102.7\n22 109.1\n23 114.8\n24 119.9\n25 125.3\n26 131.1\nAll other causes, all races, both sexes from 2020 \nLifetables, Social Security Agency\nhttps://www.ssa.gov/oact/STATS/table4c6.html\n12Percent of Survivor Cases with Sequelae by Type of \nCondition\n*Shepard et al. Pediatrics. 2005; 115:1220 -1232 https://pubmed.ncbi.nlm.nih.gov/15867028/\nOrtega -Sanchez IR et al. Clin Infect Dis. 2008;46:1 -13  https://pubmed.ncbi.nlm.nih.gov/18171206/\n**Edwards et al . J Pediatrics 1981; 99:540 -5   https://pubmed.ncbi.nlm.nih.gov/7277093/\n*** Baraff et al . PIDJ 1993;12:389 -94 https://pubmed.ncbi.nlm.nih.gov/8327300/Skin scarring 7.6        (0 -19) Included*\nSingle amputation 1.9     (0.5 -10) Included*\nMultiple amputations 1.2     (0.02 -6) Included*\nHearing loss** 8.8        (2 -20) Included*\nSignificant long term neurologic \ndisability***2.1   (0.02 -11) Included*\nInitial vaccine effectiveness by vaccine and \nserogroup\n13QUADRIVALENT MEN B PENTAVALENT\nBase -case Low High Base -case Low High Base -case Low High\nFirst DOSE Men ACWY 93% 73% 98% 94% 62% 96%\n2nd + DOSE Men ACWY 97% 73% 98% 97% 94% 99%\nFirst DOSE Men B 60% -- -- 60%\n2nd + DOSE Men B 85% 50% 99% 88% 79% 99%\nValues and assumptions on initial protection are based on various sources:\nPhase 3 noninferiority initial vaccine efficacy by single dose (at 11 -12yrs) and second -dose (16yrs) of pentavalent (Men ABCWY) vaccine as reported by Pfizer (data on \nfile).\nCohn AC, MacNeil JR, Harrison LH, et al. Active Bacterial Core Surveillance (ABCs) Team and MeningNet Surveillance Partners. Effectiveness and Duration of Protection \nof One Dose of a Meningococcal Conjugate Vaccine. Pediatrics. 2017 Feb;139(2):e20162193. doi: 10.1542/peds.2016 -2193. PMID: 28100689; PMCID: PMC8353579.\n0%20%40%60%80%100%120%\n0 1 2 3 4 5 6 7 8Residual protection\nYears after fully vaccinatedAssumption: Residual protection by vaccine \nand serogroup\n14Men ACWY Men B \nAssumptions on residual protection are based on various sources:\n•Sero -protection is assumed to persist 4 -5 years for a single dose of Men ACWY and Men ABCWY (based on hSBA sero bactericidal assay from Pfizer’s clinical trials report)\n•Duration of protection ( DoP) for pentavalent Men ABCWY vaccines is assumed to follow Men ACWY\n•Duration of protection ( DoP) for Men B is after fully immunized with 2 doses \n•The pink -shaded areas denote a higher level of uncertainty of the waning assumption beyond available surveillance or Phase 3 dat a\n•Cohn AC, MacNeil JR, Harrison LH, et al. Active Bacterial Core Surveillance (ABCs) Team and MeningNet Surveillance Partners. Effectiveness and Duration of Protection of One \nDose of a Meningococcal Conjugate Vaccine. Pediatrics. 2017 Feb;139(2):e20162193. doi: 10.1542/peds.2016 -2193. PMID: 28100689; PMCID: PMC8353579.0%20%40%60%80%100%120%\n0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15Residual Protection \nYears after vaccination with first doseDoP 1st Dose Mean DoP 2nd Dose Mean\n15Cost of vaccination per vaccine type, cost per \ndose* and vaccine administration setting\n* 2023 public and private sector cost per dose; VFC Current CDC Vaccine Price List, CDC. Although not included in these costs , rates and costs \nof moderate and severe adverse event were taken from the UK experience with MCC\nTrotter et al., BMJ 2002; Ortega -Sanchez et al., CID2008.  They were applied to all vaccines\n**Proportions of vaccine purchased at public and private sector and procurement from either private or private providers were based on \ndifference sources (i.e., Glazner et al., Pediatrics 2009)\n*** Calculated using a hypothetical range of prices as released by Pfizer Inc. for Men ABCWY.Quadrivalent (Q) Men B (B) Pentavalent (P)\npublic sector cost for vaccine $105.6 $141.84 $230.0\npublic sector admin cost $15.0 $15.0 $15.0\nprivate sector cost for vaccine $156.0 $211.32 $250.0\nprivate sector admin cost $30.0 $30.0 $30.0\n% vaccine purchased at public sector price 53.75% 53.75% 53.75%\n% vaccine purchased at private sector price 46.25% 46.25% 46.25%\n% vaccinations obtained from public health clinics 22% 22% 22%\n% vaccinations obtained from private sector providers 78% 78% 78%\n% vaccine waste 4.5% 4.5% 4.5%\nWeighted cost per dose + administration$162.61 \n($128 -$191)$ 209.70 \n($155 -$250) $277.92***\n($255 -$290) \n16Other Benchmark Elements\nSources: Shepard et al. Pediatrics. 2005; 115:1220 -1232 https://pubmed.ncbi.nlm.nih.gov/15867028/\nOrtega -Sanchez IR et al. Clin Infect Dis. 2008;46:1 -13  https://pubmed.ncbi.nlm.nih.gov/18171206/•Meningococcal disease incidence under vaccination\n•Direct and Indirect costs of meningococcal disease\n•Acute phase costs and long -term costs\n•Productivity loss to deaths and sequelae\n•Health related quality -of-life scores for estimating QALYs lost to sequelae\nProgram impact and cost -effectiveness then calculated by considering\nIncremental Cost -effectiveness ratios \nMonetary and quality -of-life costs associated with health outcomes\nCost of vaccination program including AEs\nQuality of life outcomes \n17Components of cost of illness calculation\nOutcomeMed care\n(mening )Parents’ \nWork -LossMed care \nsequelaeLifetime care \n(rehab, long term \ncare)**Productivity \nLoss\nNo Sequelae (acute \nphase√ √\nDeath √ √ √\nSkin scarring √ √ √\nSingle amput √ √ √ √\nMulti amput √ √ √ √ √\nHearing loss √ √ √ √\nNeuro seq √ √ √ *** √Acute phase* Lifetime\n*Includes caregivers' work time loss and public health response in outbreaks\n** Includes special education for neurologic disability, prosthesis & rehabilitation for amputations, etc.\n*** Significant neurologic disability lifetime medical costs were calculated and then annualized\nSources: Shepard et al. Pediatrics . 2005; 115:1220 -1232 https://pubmed.ncbi.nlm.nih.gov/15867028/\nOrtega -Sanchez IR et al. Clin Infect Dis. 2008;46:1 -13  https://pubmed.ncbi.nlm.nih.gov/18171206/\nSelected Cost of Meningococcal -Associated \nEvents*\nEvent / Cost Base -case Range for SA\nInvasive meningococcal disease\nMedical costs $48,983 $24,459 -$87,790\nPublic health response costs $13,547 $1,791 -$16,008\nValue of work time lost by caregivers (acute phase) $4,160\nSkin scarring\nMedical care $7,436 $6,849 -$11,153\nSingle amputation\nMedical care $23,050 $11,525 -$34,575\nOther (prosthesis & rehabilitation) $180,446 $90,222 -$270,668\nValue of permanent disability Age-specific\nMultiple amputations\nMedical care $27,662 $13,830 -$41,491 \nOther (prothesis & rehabilitation) $216,535 $108,267 -$324,802\nValue of permanent disability Age-specific\nHearing loss\nMedical care $89,566 $26,190 -$113,441\nValue of permanent disability Age-specific\nLong -term neurologic disability \nResidential care $2,704,703 $923,013 -$3,288,152\nSpecial education $204,014 $123,350 -$245,230\nValue of permanent disability Age-specific\nPremature death \n11-17 yrs $1,657,326\n18-24 yrs $1,734,664\n* Costs were in 2022 US dollars and were adjusted for their social constant value in the economy using the Gross Domestic Pro duct (GDP) deflator.  \nSources: various source and some unit costs were obtained after sequalae specific intermediate estimations  18\n19Productivity Loss\n•Incurred in cases with premature death or permanent sequelae:\n•Acute phase \n•Time of work missed Caregiver\n•Death \n•Labor market earnings + household production*                   Patient           \n•Neurologic sequelae\n•Labor market earnings* Patient  & caregiver\n•Multiple amputations\n•30% of labor market earnings** Patient\n•Hearing loss\n•33% of labor market earnings** Patient\n*Reported in  Grosse SD, et al . J Med Econ. 2019 Jun;22(6):501 -508.. https://pubmed.ncbi.nlm.nih.gov/30384792/\nValues were adjusted to 2022 US$. Age -specific values, US population, 3% discount rate\n** Shepard et al. Pediatrics . 2005; 115:1220 -1232 https://pubmed.ncbi.nlm.nih.gov/15867028/\nOrtega -Sanchez IR et al. Clin Infect Dis. 2008;46:1 -13  https://pubmed.ncbi.nlm.nih.gov/18171206/\n20Health -related Quality of Life QALY Scores*\nBase case High Low\nBaseline utilities 11 -25 years old ** 0.92\nSurvivor of IMD without sequalae (first year only) *** 0.91 0.88 0.94\nDeath 0\nSkin scarring 0.95 1.00 0.80\nSingle amputation 0.70 0.80 0.31\nMultiple amputations 0.61 0.71 0.31\nHearing loss/cochlear implants 0.72 0.82 0.64\nNeurologic disability 0.06 0.39 0.00\n*Several sources cited in: Shepard et al. Pediatrics . 2005; 115:1220 -1232 https://pubmed.ncbi.nlm.nih.gov/15867028/\nOrtega -Sanchez IR et al. Clin Infect Dis. 2008;46:1 -13  https://pubmed.ncbi.nlm.nih.gov/18171206/\n** Age -dependent EQ -5D-5L Utilities from Jiang, R. et al. Quality of Life Research, 2020:30, 803 -816. https://pubmed.ncbi.nlm.nih.gov/33025373/\n*** Assumption based on hospitalization scores (unpublished data from a JIVE Covid utilities study. University of Michigan)\nNote: Among survivors, except those without sequelae, the specific score’ reduction is applied for the remaining lifetime of survivor   \n21Disease Incidence Under Vaccination\nFor each age group and for each vaccination strategy\nMDIvacc= MDIno vacc * [1 -VE*DoPt*Vcov ]\nWhere:\n•MDIvacc = Meningococcal disease incidence under vaccination for each type of vaccine\n•MDInovacc = Meningococcal disease incidence without vaccination\n•VE = Initial v accine efficacy from each vaccine and dose\n•DoPt = Duration of protection factor ( t= time in years after vaccination)\n•Vcov = Vaccination coverage for each vaccine and dose\nEconomic evaluation\nIncremental cost -effectiveness ratio ( ICER ) : \n𝐼𝐶𝐸𝑅=𝑁𝐶𝑝𝑒𝑛𝑡𝑎−𝑁𝐶𝑆𝑜𝐶\n𝐻𝑂𝑆𝑜𝐶−𝐻𝑂𝑝𝑒𝑛𝑡𝑎\nWhere:\n•NCpenta = Net Cost of IMD disease with new interventions               \n(vaccine program costs)\n•NCSoC = Net Cost of IMD disease costs under \nStandard of care\n•HOpenta = Health outcome using pentavalent (ex., QALYs)\n•HOSoC = Health outcome of Standard of Care (ex., QALYs) \nBoth Cost and QALYs are discounted using:\n•t = time years after immunization (t=0, 1, 2,…, T)\n•r  = discount rate (3%)\n•T = Analytical horizon (age -specific, in years)Number needed to vaccinate (NNV) ratio : \n𝑁𝑁𝑉=#𝑉𝑎𝑐𝑐𝑖𝑛𝑒𝑒𝑠\n#𝐻𝑂𝑠𝑎𝑣𝑒𝑑\nWhere:\n•# Vaccinees = Number of individuals vaccinated \nagainst IMD during the time frame of the \nintervention\n•#HOsaved = Number of health outcomes saved or \nprevented with vaccination, ex.,  \n•Acute IMD cases prevented\n•Life-years prevented\n•lives saved\n23Results*\n* Preliminary\nExpected Cumulative Annual IMD Cases* and Deaths** \nwithout vaccination in 11 –25-years old*\n24120400\n11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26Cumulative number of IMD cases ( in logarithms ) \nAge in yearsMen ABCWY\nMen ACWY\nMen B\n010203040506070\n11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26Cumulative number of IMD deaths \nAge in yearsMen ABCWY\nMen ACWY\nMen B\n* Using IMD incidence data from 1996 -2005 (pre -vaccine) for serogroups CWY and 1994 -2013 (pre -vaccine) for serogroup B\n** Using CFR data is from NNDSS for 2008 -2020\nCumulative Number of IMD Cases Saved: Vaccination \nstrategy -and age -specific*\n*Estimates from Monte Carlo Simulation\n** Rounded to the nearest whole number25StrategyMean** \n(5th& 95thpercentiles)\nP-P-P229 \n(191 –273)\nQ-P-B228 \n(190 –278)\nP-P-N229 \n(189 –276)\nQ-P-P226\n(185 –270)\nSoC207\n(163 –252)\nQ-Q194 \n(156 –241)\n050100150200250300\n11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26Cumulative number of IMD cases saved by Vaccine\nAge in yearsP-P-P\nQ-P-B\nP-P-N\nQ-P-P\nSoC\nQ-Q\nB-B\n0510152025303540\n11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26Cumulative number of IMD deaths saved by Vaccine\nAge in yearsP-P-P\nQ-P-B\nP-P-N\nQ-P-P\nSoC\nQ-Q\nB-BCumulative Number of IMD deaths prevented: \nVaccination strategy -and age -specific*\n*Estimates from Monte Carlo Simulation\n**  Rounded to the nearest whole number26StrategyMean** \n(5th, 95thpercentiles)\nP-P-P32 \n(25 –40)\nQ-P-B32 \n(25 –40)\nP-P-N32 \n(25 –41)\nQ-P-P31\n(25 –40)\nSoC30\n(23 –37)\nQ-Q27 \n(21 –36)\nNumber needed to vaccinated to prevent a case, \nsave a life, a life -year or a quality -adjusted life year\nWith\nMen ACWY \n(Q-Q)With Men B\n(B-B) Q-P-B P-P-P\nA IMD Case 19,034 292,559 16,144 16,085\nA Death 133,981 1,810,451 115,450 115,086\nA Life -year 4,644 63,695 4,763 4,745\nA QALY 2,609 38,169 2,694 2,682\n*   Estimates from Monte Carlo Simulation\nMen ABCWY = Potential pentavalent vaccine (P) with serogroups A, B, C ,W and Y\nMen ACWY = Quadrivalent vaccine (Q)  for serogroups A,  C, W, and Y , \nMen B =Meningococcal serogroup B vaccine (B)\n27\nBaseline of SoC: Health outcomes, Vaccine and \nNet Costs per ~4M Cohort, Mean (5th,95thPercentile)*\nNo Vaccine BCWYPrevention with\nMen ACWY  (Q -Q) \nVaccine & Net CostsPrevention with \nMen B  (B -B)\nVaccine & Net Costs SoC\nIMD Cases428\n(296 -604)194\n(156 –241)13\n(7 –21)207\nDeaths68\n(44 -95)28\n(21 –36)2\n(1 –4)30\nLife years ***1,938\n(1252 -2,701)796\n(592 –1,035)58\n(31 –98)854\nQALY’s ***3,306\n(3,084 -4,513)1,416\n(1,090 –1,800)97\n(53 –164)1,513\nVaccination program costs \n(in Millions $) 0.0$1,120.4  \n(826.9 –1,471.5)$1,492.7 \n(1,061.2 –2,18.6)$2,613.0\nTotal net cost of illness \n(in Millions $) ***$270 \n($178 -$379)$997.5 \n(667.0 –1,325.5)$1,485.0 \n(1,053.8 –2.011.3)$2,482.5\n*Estimates from Monte Carlo Simulation\n**  Health outcomes were rounded to the nearest whole number \n**Discounted at 3%28\nHealth outcomes saved and Net Cost per 4M Cohort of \n11yrs followed until 25yrs: Mean (5th, 95thPercentile)*\nSoCQ-P-B\n(for Pico 1) P-P-P Q-QP-P-N\n(for Pico 2)\nIMD Cases207 229\n(190 –278)229\n(191 –273)194\n(156 –241)229\n(189 –276)\nDeaths30 32\n(25 –40)32\n(25 –40)27\n(21 –36)32\n(25 –41)\nLife years saved ***854 775\n(585 –1,000)777\n(584 –995)796\n(590 –1,035)778\n(577 –1,012)\nQALY’s saved***1,513 1,370\n(1,059 –1,7281,376\n(1,065 –1,762)1,417\n(1,090 –1,800)1,375\n(1,058 –1,742)\nVaccination program \ncosts (in Millions $) $2,613.0 $2,129\n(1,870 –2,425)$2,788.8 \n(2,602.5 –2,983)$1,120.4  \n(826.9 –1,472)$1,915.9\n(1,788 –2,049)\nTotal net cost of illness \n(in Millions $) ***$2,482.5 $1,986.4 \n(1,695 –2,265)$2,645.6 \n(2,469 –2,847)$968.2 \n(703.0 –1,348)$1,773\n(1,643 –1,906)\n29*   Estimates from Monte Carlo Simulation\n**  Health outcomes were rounded to the nearest whole number \n** Discounted at 3%\nIncremental Cost per QALY saved by each vaccination \nstrategy when compared to No vaccination*\n*Estimates from Monte Carlo Simulation, numbers were rounded to nearest thousand\nThe pink -shaded areas highlight comparison that would corroborate the incremental analysis results  30$550,000$17,082,000\n$1,498,000\n$1,126,000\n100,0001,000,00010,000,000100,000,000\nQ-Q B-B SoC P-P-NCost per QALY saved ( in logarithms )\n$1,498,000\n$1,290,000$1,517,000$1,775,000\n700,0001,200,0001,700,0002,200,0002,700,000\nSoC Q-P-B Q-P-P P-P-PCost per QALY saved$1,498,000$17,082,000\n$550,000$1,126,000\n100,0001,000,00010,000,000100,000,000\nSoC B-B Q-Q P-P-NCost per QALY saved ( in logarithms )\nIncremental Cost -Effectiveness Analyses for QALYs \nand Life -years saved ( in thousands $ )\n*Estimates from Monte Carlo Simulation  (Discounted at 3%)\n** the $/LY gained of P -P-N vs SoC strategy could be marginally cost-saving: Mean $/LY <0, but its 5thand 95thpercentiles from simulation range from <0 to costly\nNote: SoC            = Standard of care = one quadrivalent dose 11 -12yrs and second at 16yrs (= Q -Q) and2 doses Men B at 16yrs (= B -B)\nCost-saving          = a strategy could be said to be dominant when is cost -saving 31Q-P-B vs. SoC\n(Pico 1)P-P-P vs. SoCP-P-N vs. Q -Q\n(Pico 2)\nICER QALY saved*Q-P-B \nis cost -saving \n(Cost <0)P-P-P is \nincrementally costly\n$1,455P-P-N \nIs incrementally costly\n$2,936\nICER LY saved*Q-P-B\nis cost -saving \n(Cost <0 ) P-P-P could be cost saving \n(Cost ≤0)**\n(Range from cost -saving to costly)P-P-N \nis incrementally costly\n$4,563 Q-P-B vs. \nNo vaccinationSoC vs \nNo vaccinationP-P-P vs \nNo vaccinationP-P-N vs. \nNo vaccinationQ-Q vs. \nNo vaccination\n$/QALY saved*$1,256 $1,461 $1,730 $1,096 $534\n$/ LY saved$2,563 $2,908 $3,401 $2,279 $1,254\nProbability of Incremental Cost -Effectiveness ratio \nper QALY saved: Q -P-B vs SoC: $/QALY<0 (Pico 1)\n32-8.12 -0.58\n5.0% 5.0% 90.0%\n0.00.20.40.60.81.0\n-10\n-8\n-6\n-4\n-2\n0\n2\n4\n6\nValues in Millions ($)Q-P-B-vs-SoC: Cumulative Probability of ICER per QALY saved* \n*Estimates from Monte Carlo Simulation using a sample of 1000 iterations (Costs were discounted at 3%)\nRange are 5thand 95thpercentiles •Both 5thand 95th\npercentiles are \nnegative (i.e., cost \nsaving)\n•More than 95% of the \niterations were  \nnegative (i.e., cost \nsaving)\nSensitivity of Incremental Cost -Effectiveness ratio per \nQALY saved: P -P-N vs Q -Q  $2.9M/QALY gained (Pico 2)\n33\n\n34Strengths and Limitations\nStrengths\n•Complex modeling \n•Explicit use of incidence and CFR surveillance data for Men BCWY vaccine -\ncontaining serogroups\nLimitations\n•Data on vaccine effectiveness from pentavalent Men BCWY are from clinical trials\n•Hard to ascertain decrease in IMD incidence rates due to natural decline trend vs. \nvaccine induced decline\n•Variability of vaccine uptake per type of vaccine\n35Conclusions \n•Disease rates and vaccine cost drive the incremental analyses\n•Although additional cases could be prevented by all vaccination \nstrategies, they do it at different costs per health outcome\n•Most strategies with one or more doses of the Men ABCWY vaccine would \nsave more or equal number of cases, but they do at a much higher costs per \nQALY saved when compared to the standard of care.\n•The exception is the Q -P-B, which included one dose of Men ABCWY in \nsubstitution of the second dose of Men ACWY and first dose of Men B.\n•Q-P-B  could be incrementally cost -saving (ICER QALY <0) relative to the \nstandard of care\n•Using last 10 years of epidemiology data and current (or proposed) \nvaccine prices increase the cost of all strategies compared to previous \nanalyses\nEnd of Presentation\n\nIncidence rate of IMD for serogroups CWY 1996 -\n2005 and 1996 -2020 by age per 100,000\n0.000.200.400.600.801.001.201.401.60\n=<10 11 12 13 14 15 16 17 18 19 20 21 22 >=23IMD incidence rate for serogroups CWY per 100,000\nAgeMean CWY 1996-2005\nMedian CWY 1996-2005\nMean CWY 1996-2020\nMedian CWY1996-2020\nIncidence rates from 1996 -2005 for the Pre vaccine Era are from the ABC core surveillance \nIncidence rates from 1996 to 2020 combined data from ABC and NNDSS.  37\nIncidence rate of IMD for serogroup B before \nand during vaccine era by age per 100,000\n00.050.10.150.20.250.30.35\n11-12 years 13-14 years 15-16 years 17-18 years 19-20 years 21-22 years 23-24 yearsIMD incidence rate for serogroup B  per 100,000\nAgeABC-1994-2013\n2014-2016\n2017-2019\n2020-2022 Pre\nData from 1994 -2013 are from the ABC core surveillance, Data from 2014 -2019 are from the NNDSS.  \nData from 2020 -2022 also from NNDSS is preliminary 38\nIncidence rate of IMD for serogroups CWY  before \nand during vaccine era by age per 100,000\n0.010.101.0010.00\n=<10 11 12 13 14 15 16 17 18 19 20 21 22 >=23IMD incidence per 100,000(n logarithms)\nAgeMean CWY 1996-2005\nMedian CWY 1996-2005\nMean CWY 2005-2020\nMedian CYW 2005-2020\n39", "summary": "The Cost -effectiveness of a Potential Pentavalent  Meningococcal Conjugate Vaccine (Men ABCWY)  versus the Current Men ACWY and Men B  vaccines for US Adolescents  Ismael R. Ortega -Sanchez, PhD CDC/NCIRD ACIP meeting, June 23, 2023 Disclaimer : The findings and conclusions in this report are those of the authors and do not necessarily  represent the views of the Centers for Disease Control and Prevention. 1  2Conflict of Interest CDC/NCIRD collaborators:  All collaborators, No conflict of…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/02-Mening-Ortega-Sanchez-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 39}
{"title": "03 Mening Crowe 508", "content": "National Center for Immunization & Respiratory Diseases\nEvidence to Recommendations Framework:\nPfizer’s MenABCWY Vaccine\nSam Crowe, PhD, MPH\nMeningococcal Vaccines Work Group Lead\nJune 23, 2023\n\nOutline\n▪Overview of policy questions and PICOs\n▪Evidence to Recommendations framework\n▪Summary of findings\n▪WG proposed options\n2\nPfizer MenABCWY Vaccine\n▪Comprised of Trumenba (serogroup B) and Nimenrix (serogroups ACWY)\n–Trumenba\n•Consists of two purified recombinant lipidated FHbp antigens, one from each FHbp subfamily (A \nand B)\n•Currently licensed and available in US (10 –25 years)\n–Nimenrix\n•Meningococcal group A, C, W, and Y polysaccharide tetanus toxoid conjugate vaccine\n•Not licensed in US but used extensively in Europe and elsewhere for over a decade\n▪Clinical trial data\n–Assessed\n•Two doses (0,6 m and 0,12 m apart)\n–Studied 10 through 25 years of age\n–Both MenACWY primed and naïve subjects\n–Longer interval studies underway (not available in time for initial product licensure)\n3\nPolicy Questions for 3 PICOs \n▪Should the pentavalent vaccine be included as an option for \nMenACWY/MenB vaccination in people currently recommended to receive \nboth vaccines ? (PICO 1)\n▪Should the pentavalent vaccine be included as an option for people \ncurrently recommended to receive MenACWY only ? (PICO 2)\n▪Should the pentavalent vaccine be included as an option for people \ncurrently recommended to receive MenB only ? (PICO 3)\n4\nGRADE Table 1: Combined Policy Question and PICO\nPolicy QuestionShould the pentavalent vaccine be included as an option for people currently recommended to receive \nMenACWY and MenB, MenACWY only, or MenB only ?\nPopulationAll individuals aged 10 years or older currently recommended to receive MenACWY+MenB, MenACWY , or \nMenB vaccine\nIntervention Vaccination with the pentavalent vaccine\nComparison Vaccination with currently licensed MenACWY+MenB, MenACWY , or MenB vaccine\nOutcomes•Meningococcal disease caused by serogroups A, B, C, W, and Y ( as appropriate by PICO )\n•Short -term immunity\n•Persistent immunity\n•Interference with other recommended vaccines administered concurrently\n•Serious adverse events\n•Non -serious adverse events\n5\nRoutine Schedule and Increased Risk Populations\n▪Routine schedule \n–One MenACWY dose at 11 –12 years and a booster at 16 years\n–Two MenB doses at 16 –18 years (shared clinical decision -making recommendation)\n▪Increased risk, MenACWY (vaccines are interchangeable)\n–Recommended for certain medical conditions\n•Asplenia, complement deficiency, complement inhibitor use, and HIV infection\n–Some microbiologists\n–Exposure during an outbreak\n–Travel to hyperendemic areas\n–First -year college students\n–Military recruits\n▪Increased risk, MenB (vaccines are notinterchangeable)\n–Recommended for certain medical conditions\n•Asplenia, complement deficiency, and complement inhibitor use\n–Some microbiologists\n–Exposure during an outbreak 6\nHow PICOs Translate into Schedule Options for \nHealthy Adolescents\nLegend\nQ = MenACWY (quadrivalent)\nB = MenB\nP = MenABCWY (pentavalent) 7Options11–12 year \nold dose16 year old \ndose #116 year old \ndose #2\nStandard of care (MenACWY only) Q Q –\nStandard of care (MenACWY + MenB) Q Q+B B\nPICO 1 (MenABCWY as option for MenACWY + MenB) Q P B\nPICO 2 (MenABCWY as option for MenACWY) P P B\nPICO 3 (MenABCWY as option for MenB) Q P P\nCombination of all 3 PICOs P P P\nPublic Health Problem\nIs meningococcal disease a problem of public health importance? \n9Meningococcal Disease Incidence —\nUnited States, 1996 –2022*\n0.000.200.400.600.801.001.201.40\n1996 2000 2005 2010 2015 2020 2022Incidence per 100,000\nYear\nSource : 1996 –2022 NNDSS Data. *2021 –2022 NNDSS data are preliminary.0.09 cases/100,000 \npopulationMenACWY vaccine1.2 cases/100,000 \npopulation\nMenB vaccine\n10Average Annual Meningococcal Disease Incidence by \nAge Group and Serogroup ― United States, 2010 –2022*\nSource: NNDSS data with additional serogroup data from the Active Bacterial Core Surveillance System and state health departm ents \n*2022 data are preliminary00.20.40.60.811.2\n<1 year 1 year 2-4\nyears5-10\nyears11-15\nyears16-20\nyears21-25\nyears26-44\nyears45-64\nyears65-84\nyears85+\nyearsIncidence per 100,000\nAge GroupB ACWY Oth/Unk\nEven with treatment, morbidity and mortality are high \n~10–15% \nof cases are fatal\n11\n10–20% of survivors \nhave permanent sequelaeEven with treatment, mortality and morbidity are high \n~10–15% \nof cases are fatal\n12\nSummary of the Public Health Problem  \n▪Incidence of meningococcal disease\n–Low\n–Decreasing for some time \n▪Causes very severe disease\n▪Poor outcomes even with treatment\n13\nPublic Health Problem —Work Group Interpretation\n▪Is meningococcal disease a problem of public health importance? \nNo Probably No Probably Yes Yes Varies Don’t Know\n14\nBenefits and Harms\n-How substantial are the desirable anticipated effects?\n-How substantial are the undesirable anticipated effects?\n-Do the desirable effects outweigh the undesirable effects? \nGRADE Appendix 1: Studies Included in Review of Evidence\nAuthor, Year Study Design Country AgeNumber of \nParticipants Number \nInterventionNumber \nComparisonData Sources\nPfizer (NCT04440163), \n2020RCTUS, Czech R., Denmark, \nHungary, Poland10–25 \nyears2412 1763 649Clinicaltrials.gov, \nPfizer WG and \nACIP \npresentations, \nPfizer \ncorrespondence, \nPfizer preliminary \nresults \npresentations Pfizer (NCT03135834), \n2017RCTUS, Czech R., Finland, \nPoland10–25 \nyears1600 543 1057\nPfizer (NCT04440176), \n2020RCT US11–14 \nyears294 294 N/A\n16\nGRADE Table 2: Outcomes and Rankings\nOutcome Importance Included in Profile\nMeningococcal disease caused by \nserogroups A, B, C, W, and YCritical No\nShort -term immunity Critical Yes\nPersistent immunity Important Yes\nInterference with other recommended \nvaccines administered concurrentlyImportant No\nSerious adverse events Critical Yes\nNon -serious adverse events Important Yes\n17\nComplexity of Review\n▪Four outcomes of interest in evidence profile\n–Short -term immunity\n–Persistent immunity\n–Serious adverse events\n–Non -serious adverse events\n▪Three PICO questions\n–PICO 1: MenABCWY as an option for MenACWY+MenB\n–PICO 2: MenABCWY as an option for MenACWY\n–PICO 3: MenABCWY as an option for MenB\n▪Two populations\n–Healthy individuals 10 years old or older\n–People with medical conditions that put them at increased risk for invasive disease aged \n10 years old or older (i.e., asplenia, complement deficiency, and HIV infection)\n18\nGRADE Table 4: Short -Term Immunity for Healthy Persons —PICOs 1, 2, and 3\n19Certainty assessment № of patients Effect\nCertainty Importance\n№ of studies Study design Risk of bias Inconsistency Indirectness ImprecisionOther \nconsiderationsPfizer \nMenABCWYMenACWY \nand MenBRelative\n(95% CI)Absolute\n(95% CI)\nShort -term immunity for MenACWY (follow -up: 1 month)\n1 randomized \ntrialsnot serious not serious serious1not serious none In naïve participants, short -term immunity increases slightly for \nserogroups A, C, W, and Y at 1 month after 1 dose of \nMenABCWY versus 1 dose of MenACWY -CRM: \nSerogroup A (n=753), RR of 1.02 (95% CI: 0.99 –1.05)\nSerogroup C (n=753), RR: 1.20 (95% CI: 1.05 –1.38)\nSerogroup W (n=736), RR 1.09 (95% CI: 0.99 –1.19)\nSerogroup Y (n=742), RR 1.16 (95% CI: 1.06 –1.27)\nIn primed participants, little or no difference was observed in \nshort -term immunity for serogroups A, C, W, and Y at 1 month \nafter 1 dose of MenABCWY versus 1 dose of MenACWY -CRM: \nSerogroup A (n=666), RR of 0.98 (95% CI: 0.95 –1.01)\nSerogroup C (n=665), RR: 0.99 (95% CI: 0.95 –1.03)\nSerogroup W (n=650), RR 1.01 (95% CI: 0.98 –1.04)\nSerogroup Y (n=665), RR 1.01 (95% CI: 0.97 –1.05) ⨁⨁⨁◯\nModerateCRITICAL\nShort -term immunity for MenB (follow -up: 1 month)\n1 randomized \ntrialsnot serious not serious serious1not serious none 591/755 \n(78.3%)2263/419 \n(62.8%)2RR 1.25\n(1.15 to 1.36)15,692 more \nper 100,000\n(from 9,415 \nmore to \n22,597 more)⨁⨁⨁◯\nModerateCRITICAL\n1hSBA titers are the established correlate of protection for serogroup C meningococcal disease. This correlation is assumed to exte ndto other \nserogroups, but direct evidence for these serogroups is limited. Goldschneider et al. Human immunity to the meningococcus. I. The role of humoral \nantibodies. J Exp Med . 1969;129(6):1307 –26. \n2Calculated based on serogroup B composite data. \nGRADE Table 4: Short -Term Immunity for Persons at Increased Risk —PICOs 1, 2, and 3\n20Certainty assessment № of patients Effect\nCertainty Importance\n№ of studies Study design Risk of bias Inconsistency Indirectness ImprecisionOther \nconsiderationsPfizer \nMenABCWYMenACWY \nand MenBRelative\n(95% CI)Absolute\n(95% CI)\nShort -term immunity for MenACWY (follow -up: 1 month)\n1 randomized \ntrialsnot serious not serious very \nserious1,2not serious none In naïve participants, short -term immunity increases slightly for \nserogroups A, C, W, and Y at 1 month after 1 dose of \nMenABCWY versus 1 dose of MenACWY -CRM: \nSerogroup A (n=753), RR of 1.02 (95% CI: 0.99 –1.05)\nSerogroup C (n=753), RR: 1.20 (95% CI: 1.05 –1.38)\nSerogroup W (n=736), RR 1.09 (95% CI: 0.99 –1.19)\nSerogroup Y (n=742), RR 1.16 (95% CI: 1.06 –1.27)\nIn primed participants, little or no difference was observed in \nshort -term immunity for serogroups A, C, W, and Y at 1 month \nafter 1 dose of MenABCWY versus 1 dose of MenACWY -CRM: \nSerogroup A (n=666), RR of 0.98 (95% CI: 0.95 –1.01)\nSerogroup C (n=665), RR: 0.99 (95% CI: 0.95 –1.03)\nSerogroup W (n=650), RR 1.01 (95% CI: 0.98 –1.04)\nSerogroup Y (n=665), RR 1.01 (95% CI: 0.97 –1.05) ⨁⨁◯◯\nLowCRITICAL\nShort -term immunity for MenB (follow -up: 1 month)\n1 randomized \ntrialsnot serious not serious very \nserious1,2not serious none 591/755 \n(78.3%)3263/419 \n(62.8%)3RR 1.25\n(1.15 to 1.36)15,692 more \nper 100,000\n(from 9,415 \nmore to \n22,597 more)⨁⨁◯◯\nLowCRITICAL\n1Clinical trials did not include patients at increased risk for invasive disease.\n2hSBA titers are the established correlate of protection for serogroup C meningococcal disease. This correlation is assumed to exte ndto other \nserogroups, but direct evidence for these serogroups is limited. Goldschneider et al. Human immunity to the meningococcus. I. The role of humoral \nantibodies. J Exp Med . 1969;129(6):1307 –26. \n3Calculated based on serogroup B composite data. \nGRADE Table 4: Persistent Immunity for Healthy Persons —PICOs 1, 2, and 3\n21Certainty assessment № of patients Effect\nCertainty Importance№ of studies Study design Risk of bias Inconsistency Indirectness ImprecisionOther \nconsiderationsPfizer \nMenABCWYMenACWY \nand MenBRelative\n(95% CI)Absolute\n(95% CI)\nPersistent immunity for MenACWY (follow -up: 48 months)\n1 randomized \ntrialsnot serious not serious very \nserious1,2not serious none In naïve participants, seroprotection probably increases for \nserogroups A, C, W, and Y at 48 months after 2 doses of \nMenABCWY versus 54 months after 1 dose of MenACWY -CRM: \nSerogroup A (n=112), RR of 1.29 (95% CI: 1.00 –1.67)\nSerogroup C (n=113), RR: 1.63 (95% CI: 1.06 –2.49)\nSerogroup W (n=111), RR 1.29 (95% CI: 1.05 –1.59)\nSerogroup Y (n=113), RR 1.05 (95% CI: 0.98 –1.12)\nIn primed participants, little or no difference was observed in \nseroprotection for serogroups A, C, W, and Y at 48 months after \n2 doses of MenABCWY versus 54 months after 1 dose of \nMenACWY -CRM: \nSerogroup A (n=63), RR of 1.00 (95% CI: 1.00 –1.00)\nSerogroup C (n=134), RR: 1.10 (95% CI: 1.01 –1.21) \nSerogroup W (n=63), RR 1.10 (95% CI: 0.97 –1.24)\nSerogroup Y (n=62), RR 1.00 (95% CI: 1.00 –1.00)⨁⨁◯◯\nLowIMPORTANT\nPersistent immunity for MenB (follow -up: 48 months)\n1 randomized \ntrialsnot serious not serious serious2not serious none In naïve participants, little or no difference was observed in \nseroprotection for serogroup B at 48 months after 2 doses of \nMenABCWY versus 48 months after 2 doses of MenB -FHbp : \nSerogroup B (A22) (n=233), RR of 0.88 (95% CI: 0.59 –1.31)\nSerogroup B (A56) (n=243), RR: 1.17 (95% CI: 0.80 –1.70)\nSerogroup B (B24) (n=243), RR 1.38 (95% CI: 0.93 –2.04)\nSerogroup B (B44) (n=247), RR 1.13 (95% CI: 0.64 –1.98)⨁⨁⨁◯\nModerateIMPORTANT\n1Comparisons were between 2 doses of MenABCWY and 1 dose of MenACWY -CRM. Comparisons also were staggered by 6 months.\n2hSBA titers are the established correlate of protection for serogroup C meningococcal disease. This correlation is assumed to exte ndto other serogroups, but direct \nevidence for these serogroups is limited. Goldschneider et al. Human immunity to the meningococcus. I. The role of humoral antibodies. J Exp Med . 1969;129(6):1307 –26. \nGRADE Table 4: Persistent Immunity for Persons at Increased Risk —PICOs 1, 2, and 3\n22Certainty assessment № of patients Effect\nCertainty Importance№ of studies Study design Risk of bias Inconsistency Indirectness ImprecisionOther \nconsiderationsPfizer \nMenABCWYMenACWY \nand MenBRelative\n(95% CI)Absolute\n(95% CI)\nPersistent immunity for MenACWY (follow -up: 48 months)\n1 randomized \ntrialsnot serious not serious very serious1,2,3 not serious none In naïve participants, seroprotection probably increases for \nserogroups A, C, W, and Y at 48 months after 2 doses of \nMenABCWY versus 54 months after 1 dose of MenACWY -CRM: \nSerogroup A (n=112), RR of 1.29 (95% CI: 1.00 –1.67)\nSerogroup C (n=113), RR: 1.63 (95% CI: 1.06 –2.49)\nSerogroup W (n=111), RR 1.29 (95% CI: 1.05 –1.59)\nSerogroup Y (n=113), RR 1.05 (95% CI: 0.98 –1.12)\nIn primed participants, little or no difference was observed in \nseroprotection for serogroups A, C, W, and Y at 48 months after \n2 doses of MenABCWY versus 54 months after 1 dose of \nMenACWY -CRM: \nSerogroup A (n=63), RR of 1.00 (95% CI: 1.00 –1.00)\nSerogroup C (n=134), RR: 1.10 (95% CI: 1.01 –1.21) \nSerogroup W (n=63), RR 1.10 (95% CI: 0.97 –1.24)\nSerogroup Y (n=62), RR 1.00 (95% CI: 1.00 –1.00)⨁⨁◯◯\nLowIMPORTANT\nPersistent immunity for MenB (follow -up: 48 months)\n1 randomized \ntrialsnot serious not serious very serious2,3 not serious none In naïve participants, little or no difference was observed in \nseroprotection for serogroup B at 48 months after 2 doses of \nMenABCWY versus 48 months after 2 doses of MenB -FHbp : \nSerogroup B (A22) (n=233), RR of 0.88 (95% CI: 0.59 –1.31)\nSerogroup B (A56) (n=243), RR: 1.17 (95% CI: 0.80 –1.70)\nSerogroup B (B24) (n=243), RR 1.38 (95% CI: 0.93 –2.04)\nSerogroup B (B44) (n=247), RR 1.13 (95% CI: 0.64 –1.98)⨁⨁◯◯\nLowIMPORTANT\n1Comparisons were between 2 doses of MenABCWY and 1 dose of MenACWY -CRM. Comparisons also were staggered by 6 months.\n2Clinical trials did not include patients at increased risk for invasive disease.\n3hSBA titers are the established correlate of protection for serogroup C meningococcal disease. This correlation is assumed to exte ndto other serogroups, but direct \nevidence for these serogroups is limited. Goldschneider et al. Human immunity to the meningococcus. I. The role of humoral antibodies. J Exp Med . 1969;129(6):1307 –26. \nGRADE Table 4: Serious Adverse Events for Healthy and Increased Risk —PICOs 1, \n2, and 3\n231 Comparisons were between 2 doses of MenABCWY and 1 dose of MenACWY -CRM plus 2 doses of MenB -FHbp . \n2Downgraded because relative effect confidence intervals are wide.\n3Clinical trials did not include patients at increased risk for invasive disease. Certainty assessment № of patients Effect\nCertainty Importance\n№ of studies Study design Risk of bias Inconsistency Indirectness ImprecisionOther \nconsiderationsPfizer \nMenABCWYMenACWY \nand MenBRelative\n(95% CI)Absolute\n(95% CI)\n2 randomized \ntrialsnot serious not serious serious1serious2none 13/2306 \n(0.6%) 8/1706 (0.5%) RR 1.94\n(0.72 to 5.22)441 more per \n100,000\n(from 131 \nfewer to 1979 \nmore)⨁⨁◯◯\nLowCRITICALHealthy Persons\nPersons at Increased Risk\nCertainty assessment № of patients Effect\nCertainty Importance\n№ of studies Study design Risk of bias Inconsistency Indirectness ImprecisionOther \nconsiderationsPfizer \nMenABCWYMenACWY \nand MenBRelative\n(95% CI)Absolute\n(95% CI)\n2 randomized \ntrialsnot serious not serious very \nserious1,3Serious2none 13/2306 \n(0.6%) 8/1706 (0.5%) RR 1.94\n(0.72 to 5.22)441 more per \n100,000\n(from 131 \nfewer to 1979 \nmore)⨁◯◯◯\nVery lowCRITICAL\nGRADE Table 4: Non -Serious Adverse Events Healthy and Increased Risk —PICOs \n1, 2, and 3\nHealthy Persons\nPersons at Increased Risk\n241Comparisons were between 2 doses of MenABCWY and 1 dose of MenACWY -CRM plus 2 doses of MenB -FHbp .\n2Downgraded because absolute effect confidence intervals are wide.  \n3Clinical trials did not include patients at increased risk for invasive disease. Certainty assessment № of patients Effect\nCertainty Importance№ of studies Study design Risk of bias Inconsistency Indirectness ImprecisionOther \nconsiderationsPfizer \nMenABCWYMenACWY \nand MenBRelative\n(95% CI)Absolute\n(95% CI)\nNon -serious adverse events (assessed with: All adverse events through 1 month after 2nd vaccination)\n2 randomized \ntrialsnot serious not serious serious1serious2none 581/2306 \n(25.2%) 387/1706 \n(22.7%) RR 1.31\n(1.17 to 1.47)7,032 more \nper 100,000\n(from 3,856 \nmore to \n10,662 more)⨁⨁◯◯\nLowIMPORTANT\nCertainty assessment № of patients Effect\nCertainty Importance№ of studies Study design Risk of bias Inconsistency Indirectness ImprecisionOther \nconsiderationsPfizer \nMenABCWYMenACWY \nand MenBRelative\n(95% CI)Absolute\n(95% CI)\nNon -serious adverse events (assessed with: All adverse events through 1 month after 2nd vaccination)\n2 randomized \ntrialsnot serious not serious Serious1,3serious2none 581/2306 \n(25.2%) 387/1706 \n(22.7%) RR 1.31\n(1.17 to 1.47)7,032 more \nper 100,000\n(from 3,856 \nmore to \n10,662 more)⨁◯◯◯\nVery lowIMPORTANT\n25Benefits and Harms —Work Group Interpretation\n▪How substantial are the desirable anticipated effects?\nMinimal Small Moderate Large Varies Don’t KnowPICO 1 (MenABCWY as an option for MenACWY+MenB)\nPICO 3 (MenABCWY as an option for MenB)PICO 2 (MenABCWY as an option for MenACWY)\nMinimal Small Moderate Large Varies Don’t Know\nMinimal Small Moderate Large Varies Don’t Know\n26Benefits and Harms —Work Group Interpretation\n▪How substantial are the undesirable anticipated effects?\nMinimal Small Moderate Large Varies Don’t KnowPICO 1 (MenABCWY as an option for MenACWY+MenB)\nPICO 3 ( MenABCWY as an option for MenB )PICO 2 ( MenABCWY as an option for MenACWY )\nMinimal Small Moderate Large Varies Don’t Know\nMinimal Small Moderate Large Varies Don’t Know\n27Benefits and Harms —Work Group Interpretation\n▪Do the desirable effects outweigh the undesirable effects? \nFavors \ninterventionFavors \ncomparisonFavors both Favors neither Varies Don’t KnowPICO 1 ( MenABCWY as an option for MenACWY+MenB )\nPICO 3 ( MenABCWY as an option for MenB )PICO 2 ( MenABCWY as an option for MenACWY )\nFavors \ninterventionFavors \ncomparisonFavors both Favors neither Varies Don’t Know\nFavors \ninterventionFavors \ncomparisonFavors both Favors neither Varies Don’t Know\nValues\n-Does the target population feel that the desirable effects are large relative to \nundesirable effects?\n-Is there important uncertainty about or variability in how much people value \nthe main outcomes? \nPerspective of the Target Population\n▪Limited data are available on values of the target population toward \ninclusion of the pentavalent vaccine\n▪In 2021, vaccination coverage of at least 1 dose was 89% for MenACWY \nand 31% for MenB among adolescents\n▪Limited data are available on vaccine uptake in other individuals \nrecommended to receive MenACWY or MenB vaccine\n29\nReduced Doses\n▪“Use of combination vaccines can reduce the number of injections patients receive \nand alleviate concern associated with the number of injections… The use of a \ncombination vaccine generally is preferred over separate injections of the \nequivalent component vaccines. Considerations should include provider \nassessment, patient preference, and the potential for adverse events.”1\n▪“Combination vaccines represent one solution to the issue of increased numbers \nof injections during single clinic visits and generally are preferred over separate \ninjections of equivalent component vaccines.”2\n1 General Best Practice Guidelines for Immunization. Best Practice Guidance of the ACIP. https://www.cdc.gov/vaccines/hcp/acip -recs/general -\nrecs/downloads/general -recs.pdf\n2 American Academy of Pediatrics. Red Book 2018. Report of the Committee on Infectious Diseases. 31stEd. https://seciss.facmed.unam.mx/wp -\ncontent/uploads/2021/02/Red -Book -31th -Edition.pdf 30\nValues —Work Group Interpretation\n▪Does the target population feel that the desirable effects are large relative to undesirable effects?\nNo Probably No Probably Yes Yes Varies Don’t KnowPICO 1 ( MenABCWY as an option for MenACWY+MenB )\nPICO 3 ( MenABCWY as an option for MenB )PICO 2 ( MenABCWY as an option for MenACWY )\nNo Probably No Probably Yes Yes Varies Don’t Know\nNo Probably No Probably Yes Yes Varies Don’t Know\n31\nUncertainty in How People Value the Outcomes\n▪Limited data available on how much people value the main outcomes\n▪Vaccination rates for MenACWY , a routine recommendation, are high \namong the target population\n▪Vaccination rates for MenB are considerably lower, but decisions to \nvaccinate are based on shared clinical decision -making\n–Cause for lower rates unclear: lack of interest in vaccination, lack of awareness \nof option? \n32\nValues —Work Group Interpretation\n▪Is there important uncertainty about or variability in how much people value the main outcomes? \nImportant \nuncertainty or \nvariabilityProbably important \nuncertainty or \nvariabilityProbably not \nimportant \nuncertainty or \nvariabilityNo important \nuncertainty or \nvariabilityNo known \nundesirable \noutcomesPICO 1 ( MenABCWY as an option for MenACWY+MenB )\nPICO 3 ( MenABCWY as an option for MenB )PICO 2 ( MenABCWY as an option for MenACWY )\nImportant \nuncertainty or \nvariabilityProbably important \nuncertainty or \nvariabilityProbably not \nimportant \nuncertainty or \nvariabilityNo important \nuncertainty or \nvariabilityNo known \nundesirable \noutcomes\nImportant \nuncertainty or \nvariabilityProbably important \nuncertainty or \nvariabilityProbably not \nimportant \nuncertainty or \nvariabilityNo important \nuncertainty or \nvariabilityNo known \nundesirable \noutcomes\n33\nAcceptability\n-Is the intervention acceptable to key stakeholders? \n35Stakeholder Acceptability\n▪Limited data are available on the acceptance among key stakeholders of including MenABCWY \nas an option in the current vaccination schedule\n▪Proponents for increasing MenB vaccination likely would be supportive\n–Pentavalent vaccine combines MenB (a shared clinical decision -making recommendation) \nwith MenACWY (a standard recommendation)\n–Could increase vaccination rates against serogroup B\n▪Patients who seek vaccination against all 5 serogroups also might be supportive due to the \nreduced number of doses needed (4 versus 3)\n▪Health care providers might be supportive, particularly if they could stock fewer vaccines1,2\n1CDC. Timing and Spacing of Immunobiologics : General Best Practice Guidelines for Immunization. ACIP Timing and Spacing Guidelines \nfor Immunization | CDC . \n2Hall E, Odafe S, Madden J, Schillie S. Qualitative Conceptual Content Analysis of COVID -19 Vaccine Administration Error Inquiries. \nVaccines . 2023; 11(2):254.\n36Acceptability —Work Group Interpretation\n▪Is the intervention acceptable to key stakeholders? \nNo Probably Probably Yes Yes Varies Don’t KnowPICO 1 (MenABCWY as an option for MenACWY+MenB)\nPICO 3 (MenABCWY as an option for MenB)PICO 2 (MenABCWY as an option for MenACWY)\nNo Probably No Probably Yes Yes Varies Don’t Know\nNo Probably No Probably Yes Yes Varies Don’t Know\nResource Use\n-Is the intervention a reasonable and efficient allocation of resources? \n38CDC Cost Effectiveness Model Summary\n▪Weighted cost per dose + administration\n–MenACWY: $163 ($128 –$191)\n–MenB: $210 ($155 –$250)\n–MenABCWY: $278 ($255 –$290)\n•Most MenABCWY strategies would save more or the same number of cases as the \nstandard of care, but they would do so at a much higher cost perQALY saved\n•The exception is the Q -P-B, which could be incrementally cost saving (ICER QALY <0) \nrelative to the standard of care\n39Resource Use —Work Group Interpretation\n▪Is the intervention a reasonable and efficient allocation of resources? \nNo Probably No Probably Yes Yes Varies Don’t KnowPICO 1 (MenABCWY as an option for MenACWY+MenB)\nPICO 3 (MenABCWY as an option for MenB)PICO 2 (MenABCWY as an option for MenACWY)\nNo Probably No Probably Yes Yes Varies Don’t Know\nNo Probably No Probably Yes Yes Varies Don’t Know\nEquity\n-What would be the impact on health equity? \n41Equity Considerations\n▪Limited data are available on the impact of the pentavalent vaccine on health \nequity\n▪It is not expected that the vaccine will negatively impact equity\n▪It could potentially reduce disparities among those who might be interested in \nbeing vaccinated against serogroup B but who might not receive clinical care that \nincludes discussion of the MenB vaccine \n42Equity —Work Group Interpretation\n▪What would be the impact on health equity? \nReducedProbably \nReducedProbably No \nImpactProbably \nIncreasedIncreased Varies Don’t KnowPICO 1 (MenABCWY as an option for MenACWY+MenB)\nPICO 3 (MenABCWY as an option for MenB)PICO 2 (MenABCWY as an option for MenACWY)\nReducedProbably \nReducedProbably No \nImpactProbably \nIncreasedIncreased Varies Don’t KnowReducedProbably \nReducedProbably No \nImpactProbably \nIncreasedIncreased Varies Don’t Know\nFeasibility\n-Is the intervention feasible to implement? \n44Feasibility Considerations\n▪Challenges with insurance coverage specific to the pentavalent vaccine not expected\n▪Substantial financial burdens for providers or health systems not expected\n▪Pentavalent vaccine likely would be easily integrated into providers' practices\n–Would provide additional option in current schedule\n–Administration of the pentavalent vaccine is of equal complexity as currently available vaccines \n–Barriers to stocking the pentavalent vaccine not expected\n–Unclear, however, whether providers are willing to stock three different vaccine types\n▪Providers who routinely vaccinate persons aged 16 –18 years might have an incentive to stock the \nvaccine to reduce the number of doses given to patients who prefer vaccination against all 5 \nserogroups\n45Feasibility —Work Group Interpretation\n▪Is the intervention feasible to implement? \nNo Probably No Probably Yes Yes Varies Don’t KnowPICO 1 (MenABCWY as an option for MenACWY+MenB)\nPICO 3 (MenABCWY as an option for MenB)PICO 2 (MenABCWY as an option for MenACWY)\nNo Probably No Probably Yes Yes Varies Don’t Know\nNo Probably No Probably Yes Yes Varies Don’t Know\nSummary\n47EtR Summary for PICO 1 (MenABCWY as an option for MenACWY+MenB)\nDomain Question Work Group Judgment\nPublic health problem Is meningococcal disease a public health problem? Yes\nBenefits and harmsHow substantial are the desirable anticipated effects? Small\nHow substantial are the undesirable anticipated effects? Small\nDo the desirable effects outweigh the undesirable effects? Favors intervention\nWhat is the overall certainty of the evidence profile? Varies by group\nValuesDoes the target population feel the desirable effects are large relative to \nthe undesirable effects? Probably yes\nIs there important uncertainty about or variability in how much people \nvalue the main outcomes? Probably not important \nuncertainty or variability\nAcceptability Is the intervention acceptable to key stakeholders? Probably yes or yes\nResource use Is the intervention a reasonable and efficient allocation of resources? Probably yes or yes\nEquity What would be the impact on health equity? Probably no impact or \nvaries\nFeasibility Is the intervention feasible to implement? Probably yes or yes\n48Balance of Consequences —PICO 1 (MenABCWY as an option for \nMenACWY+MenB)\nUndesirable \nconsequences  \nclearly outweigh \ndesirable \nconsequences in \nmost settings Undesirable \nconsequences \nprobably outweigh \ndesirable \nconsequences in \nmost settingsThe balance \nbetween  \ndesirable and \nundesirable \nconsequences is \nclosely balanced \nor uncertainDesirable \nconsequences  \nprobably outweigh \nundesirable \nconsequences in \nmost settingsDesirable \nconsequences \nclearly outweigh \nundesirable \nconsequences in \nmost settingsThere is \ninsufficient \nevidence to \ndetermine the \nbalance of \nconsequences\nIs there sufficient information to move forward with a recommendation? \nYes No\n49EtR Summary for PICO 2 (MenABCWY as an option for MenACWY)\nDomain Question Work Group Judgment\nPublic health problem Is meningococcal disease a public health problem? Yes\nBenefits and harmsHow substantial are the desirable anticipated effects? Minimal, small, or \nmoderate\nHow substantial are the undesirable anticipated effects? Minimal or small\nDo the desirable effects outweigh the undesirable effects? Favors intervention, \ncomparison, or both\nWhat is the overall certainty of the evidence profile? Varies by group\nValuesDoes the target population feel the desirable effects are large relative to \nthe undesirable effects? Probably yes\nIs there important uncertainty about or variability in how much people \nvalue the main outcomes? Probably important \nuncertainty or variability\nAcceptability Is the intervention acceptable to key stakeholders? Probably yes or yes\nResource use Is the intervention a reasonable and efficient allocation of resources? Probably no or no\nEquity What would be the impact on health equity? Probably increased, varies, \nor don’t know\nFeasibility Is the intervention feasible to implement? Probably yes or yes\n50Balance of Consequences —PICO 2 (MenABCWY as an option for \nMenACWY)\nUndesirable \nconsequences  \nclearly outweigh \ndesirable \nconsequences in \nmost settings Undesirable \nconsequences \nprobably outweigh \ndesirable \nconsequences in \nmost settingsThe balance \nbetween  \ndesirable and \nundesirable \nconsequences is \nclosely balanced \nor uncertain Desirable \nconsequences  \nprobably outweigh \nundesirable \nconsequences in \nmost settingsDesirable \nconsequences \nclearly outweigh \nundesirable \nconsequences in \nmost settingsThere is \ninsufficient \nevidence to \ndetermine the \nbalance of \nconsequences\nIs there sufficient information to move forward with a recommendation? \nYes No\n51EtR Summary for PICO 3 (MenABCWY as an option for MenB)\nDomain Question Work Group Judgment\nPublic health problem Is meningococcal disease a public health problem? Yes\nBenefits and harmsHow substantial are the desirable anticipated effects? Minimal\nHow substantial are the undesirable anticipated effects? Minimal to small\nDo the desirable effects outweigh the undesirable effects? Favors intervention or \ncomparison\nWhat is the overall certainty of the evidence profile? Varies by group\nValuesDoes the target population feel the desirable effects are large relative to \nthe undesirable effects? Probably yes or don’t know\nIs there important uncertainty about or variability in how much people \nvalue the main outcomes? Important or probably \nimportant\nAcceptability Is the intervention acceptable to key stakeholders? Don’t know\nResource use Is the intervention a reasonable and efficient allocation of resources? Probably yes or yes\nEquity What would be the impact on health equity? Don’t know\nFeasibility Is the intervention feasible to implement? Probably yes or yes\n52Balance of Consequences —PICO 3 (MenABCWY as an option for MenB)\nUndesirable \nconsequences  \nclearly outweigh \ndesirable \nconsequences in \nmost settings Undesirable \nconsequences \nprobably outweigh \ndesirable \nconsequences in \nmost settingsThe balance \nbetween  \ndesirable and \nundesirable \nconsequences is \nclosely balanced \nor uncertain Desirable \nconsequences  \nprobably outweigh \nundesirable \nconsequences in \nmost settings Desirable \nconsequences \nclearly outweigh \nundesirable \nconsequences in \nmost settings There is \ninsufficient \nevidence to \ndetermine the \nbalance of \nconsequences\nIs there sufficient information to move forward with a recommendation? \nYes No\nProposed Options\n54Work Group Interpretation, PICO 1\nWe do not recommend the intervention, but it may be used within FDA licensed indications\nWe recommend the intervention for individuals based on shared clinical decision -making\nWe recommend the intervention▪Should the pentavalent vaccine be included as an option for MenACWY/MenB \nvaccination in people currently recommended to receive both vaccines ?\n55Work Group Interpretation, PICO 2\nWe do not recommend the intervention, but it may be used within FDA licensed indications\nWe recommend the intervention for individuals based on shared clinical decision -making\nWe recommend the intervention▪Should the pentavalent vaccine be included as an option for people \ncurrently recommended to receive MenACWY only ? \n56Work Group Interpretation, PICO 3\nWe do not recommend the intervention, but it may be used within FDA licensed indications\nWe recommend the intervention for individuals based on shared clinical decision -making\nWe recommend the intervention▪Should the pentavalent vaccine be included as an option for people \ncurrently recommended to receive MenB only ? \n▪WG was divided on this option, but a small majority were in favor of not \nproposing\n▪WG agreed to have ACIP consider the strengths and weaknesses of this \noption\nSchedule Options\nLegend\nQ = MenACWY (quadrivalent)\nB = MenB\nP = MenABCWY (pentavalent) 57Options11–12 year \nold dose16 year old \ndose #116 year old \ndose #2WG \nDecision\nStandard of care (MenACWY only) Q Q – N/A\nStandard of care (MenACWY + MenB) Q Q+B B N/A\nPICO 1 (MenABCWY as option for MenACWY + MenB) Q P B\nPICO 2 (MenABCWY as option for MenACWY) P P B\nPICO 3 (MenABCWY as option for MenB) Q P P\nCombination of all 3 PICOs P P P\n\n58Draft Proposal to the ACIP\n▪Forindividuals aged 10 years or older, Pfizer’s MenABCWY vaccine may be used as an alternative to \nMenACWY and MenB vaccines only when both vaccines are indicated to be given at the same time. \nThis proposal applies to healthy individuals (routine schedule) and those at increased risk for \nmeningococcal disease.\n59Draft Proposal to the ACIP\n▪Forindividuals aged 10 years or older, Pfizer’s MenABCWY vaccine may be used as an alternative to \nMenACWY and MenB vaccines only when both vaccines are indicated to be given at the same time. \nThis proposal applies to healthy individuals (routine schedule) and those at increased risk for \nmeningococcal disease.\n–Remarks:\n•This proposal is not intended to supersede or negate the shared clinical decision -making \nrecommendation for MenB. \n•The licensed MenB vaccines are not interchangeable, so use of the Pfizer pentavalent vaccine for \nthe first MenB dose would require subsequent doses to be a Pfizer MenB -FHbp vaccine or \npentavalent Pfizer MenB -FHbp -containing vaccine. \n•The minimum interval for the Pfizer pentavalent vaccine is 6 months. Individuals at increased risk of \nmeningococcal disease who are recommended to receive additional doses of MenACWY and MenB \nless than 6 months after a dose of pentavalent meningococcal vaccine should instead receive \nseparate MenACWY and MenB -FHbp vaccines.\n•The workgroup will review extended interval data when available in anticipation that this may \nprovide support for updated schedules that provide protection for all 5 serogroups. \nStrengths and Weaknesses of Q -P-B (PICO 1)\n▪ Strengths\n– Reduces doses from 4 to 3\n– Cost savings \n• ~$95 per person for the routine schedule\n• Q-Q-B-B (~$746) vs. Q -P-B (~$651)\n– CostperQALY saved less than standard of care\n– Relatively straightforward proposal\n▪ Weaknesses\n– Does not match dosing used in clinical trials (2 doses at 0,6m) \n– Would require stocking 3 vaccine types (MenACWY , MenABCWY , MenB), which might not be acceptable to some clinicians\n– Some clinics might not have funds available to stock multiple formulations, which could increase inequities\n– Could be challenging for some recipients to complete MenB series if provider does not carry MenB -FHbp\n– If ACIP does not recommend second dose of MenABCWY , insurance companies might not cover it in lieu of MenB\n– Potentially could increases risk of provider vaccine administration error1,2\n601CDC. Timing and Spacing of Immunobiologics : General Best Practice Guidelines for Immunization. ACIP Timing and Spacing Guidelines for Immunization | CDC . \n2Hall E, Odafe S, Madden J, Schillie S. Qualitative Conceptual Content Analysis of COVID -19 Vaccine Administration Error Inquiries. Vaccines . 2023; 11(2):254.\nStrengths and Weaknesses of Q -P-P (PICO 3)\n▪ Strengths\n–Reduces doses from 4 to 3\n–Small cost savings \n•~$27 per person for the routine schedule\n•Q-Q-B-B (~$746) vs. Q -P-P (~$719)\n–Relatively straightforward proposal\n–Potentially allows stocking two vaccines for most patients\n–Matches dosing used in clinical trials (2 doses at 0,6m) \n▪ Weaknesses\n–Persons needing 3 doses of MenB would still need Trumenba because of 6m minimum interval\n–Less cost savings than Q -P-B\n–Higher cost perQALY saved compared to standard of care\n–Concerns from WG that this option could lead to MenB vaccine being discontinued (but need for \nTrumenba for persons at increased risk might reduce likelihood)\n61\nComparison of Q -P-B and Q -P-P\nCriteria Q-P-B Q-P-P\nNumber of doses saved 1 1\nCost savings per person compared to standard of care $95 $27\nLess cost perQALY saved than standard of care Yes No\nNumber of vaccine types required for the routine schedule 3 2\nNumber of vaccines types required for the increased -risk schedule 3 3\nMatches dosing used in clinical trials No Yes\nUnnecessary doses of one or more serogroups No Yes\n62\n63Acknowledgments\n▪ ACIP Members on the WG\n–Kathy Poehling (Chair)\n–Lynn Bahta\n–Jamie Loehr\n▪ Ex Officio WG Members\n–Margaret Bash (FDA)\n–Mark Connelly (FDA)\n–Francisco Leyva (NIH)\n▪ WG Liaisons and Consultants\n–Amra Resic (AAFP)\n–Samir Shah (AAP) \n–Sharon McMullen (ACHA)\n–Cacky Tate (AIM)\n–Paul Cieslak (CSTE)\n–Kathy Hsu (IDSA)\n–Joseline Zafack (NACI)\n–Jeff Goad (NFID)\n–Jessica Cataldi (PIDS)\n–Amy Middleman (SAHM)\n–David Stephens (Emory)▪ CDC Contributors\n–Jenn Collins (DBD/NCIRD)\n–Lucy McNamara (DBD/NCIRD)\n–LeAnne Fox (DBD/NCIRD)\n–Susan Hariri (DBD/NCIRD)\n–Amy Rubis (DBD/NCIRD)\n–Noele Nelson (DBD/NCIRD)\n–Alison Albert (DBD/NCIRD)\n–Angela Jiles (DBD/NCIRD)\n–Jonathan Duffy (DHQP/NCEZID)\n–Tanya Myers (DHQP/NCEZID) \n–Ismael Ortega -Sanchez (DVD/NCIRD)\n–Liz Velazquez (ISD/NCIRD)\n–Jessica MacNeil (ACIP Secretariat)\n▪ GRADE/EtR Support\n–Doug Campos -Outcalt (Arizona)\n–Rebecca Morgan (Case Western Reserve)\nBackup Slides\nEvidence Retrieval\n▪Systematic review of studies in any language from Medline, Embase, \nGlobal Health, CINAHL, Cochrane, Scopus, and clinicaltrials.gov databases \nusing search string:\n–meningococcal pentavalent, pentavalent meningococcal, Pfizer pentavalent meningococcal, \nMenABCWY , Pfizer MenABCWY , pentavalent MenABCWY , \nABCWY , MenABCWY meningococcal, Neisseria meningitidis group A, B, C, W, and Y , Neisseria \nmeningitidis A, B, C, W, and Y , Neisseria meningitidis pentavalent, bivalent RLP2086 -containing \npentavalent, NCT03135834, B1971057, NCT04440163, C3511001, NCT04440176, C3511004, and \n“vaccin *” \n▪Efforts made to obtain unpublished or other relevant data\n▪Included results that presented primary data on Pfizer’s MenABCWY \nvaccine\n65\nEvidence Screening Steps\nMaterials shared by \nPfizer (n=5)References identified \nin database search \n(n=43)\nTitle and abstract \nscreening (n=43)\nFull-text article or \npublic data screening \n(n=14)\nRecords excluded \n(n=10)Records excluded \n(n=29)\nData sources included \nin GRADE analysis: 9 \n(documenting results \nof 3 clinical trials)66\nGRADE Certainty of Evidence Categories\nEvidence \nTypeStudy Design\nHighRandomized controlled trials (RCTs) or overwhelming evidence \nfrom observational studies\nModerateRCTs with important limitations, or exceptionally strong \nevidence from observational studies\nLow Observational studies, or RCTs with notable limitations\nVery lowClinical experience and observations, observational studies with \nimportant limitations, or RCTs with several major limitations\n67\nShort -Term Immunity Key Findings (Table 3a)\nAuthor, \nPub yearAgeSerogroup \n(Test strain)n/N \nABCWYn/N \ncomparisonIntervention \nvaccineComparator \nvaccine% (95% CI) for \nintervention% (95% CI) for \ncomparator Effect estimate —\nRR (95% CI)\nSeroresponse based on hSBA titer11 month after 1 intervention dose\nPfizer CT \n(NCT04440163), \n202010–25 years; \nACWY naïveA 484/499 242/254\nMenABCWY (1 \ndose)MenACWY -\nCRM (1 dose) \n+ MenB -\nFHbp (1 \ndose) 97.0% (95.1 –98.3) 95.3% (91.9 –97.5) 1.02 (0.99 –1.05)\nC 315/501 132/252 62.9% (58.5 –67.1) 52.4% (46.0 –58.7) 1.2 (1.05 –1.37)\nW 390/492 178/244 79.3% (75.4 –82.8) 73.0% (66.9 –78.4) 1.09 (0.99 –1.19)\nY 405/494 175/248 82.0% (78.3 –85.3) 70.6% (64.5 –76.2) 1.16 (1.06 –1.27)\n10–25 years; \nACWY primedA 416/439 220/227 94.8% (92.2 –96.7) 96.9% (93.7 –98.8) 0.98 (0.95 –1.01)\nC 410/439 214/226 93.4% (90.7 –95.5) 94.7% (90.9 –97.2) 0.99 (0.95 –1.03)\nW 417/428 214/222 97.4% (95.4 –98.7) 96.4% (93.0 –98.4) 1.01 (0.98 –1.04)\nY 417/442 209/223 94.3% (91.8 –96.3) 93.7% (89.7 –96.5) 1.01 (0.97 –1.05)\nSeroresponse based on hSBA titer 1 month after 2 intervention doses\nPfizer CT \n(NCT0444016\n3), 202010–25 years; \nB naïve2B (A22) 646/778 313/396\nMenABCWY \n(2 doses 6 \nmonths \napart)MenACW\nY-CRM (1 \ndose) + \nMenB -\nFHbp (2 \ndoses 6 \nmonths \napart)83% (80.2 –85.6) 79.0% (74.7 –82.9) 1.05 (0.99 –1.12)\nB (A56) 774/807 378/400 95.9% (94.3 –97.2) 94.5% (91.8 –96.5) 1.01 (0.99 –1.04)\nB (B24) 567/833 239/418 68.1% (64.8 –71.2) 57.2% (52.3 –62.0) 1.19 (1.08 –1.31)\nB (B44) 731/845 332/419 86.5% (84.0 –88.7) 79.2% (75.0 –83.0) 1.09 (1.03 –1.15)\nB (composite) 591/755 263/419 78.3% (75.2 –81.2) 68.7% (63.8 –73.3) 1.25 (1.15 –1.35)\n681hSBA = serum bactericidal assay using human complement. For participants with a baseline hSBA titer <1:4, seroresponse is defined as a titer ≥1:16. For those with a baseline hSBA titer ≥1:4 and \n<1:8 (<1:16 for A22), seroresponse is a titer ≥4 times the 1:8 (1:16 for A22). For those with a baseline hSBA titer ≥1:8 (≥1:16 for A22), seroresponse is a titer ≥4 times the baseline titer. \n2Serogroup B primed not assessed.\nPersistent Immunity Key Findings (Table 3b)\nAuthor, pub year AgeSerogroup \n(Test strain)n/N \nMenABCWYn/N \ncomparisonIntervention \nvaccine Comparator \nvaccine% (95% CI) for \nintervention% (95% CI) for \ncomparator Effect estimate —\nRR (95% CI)\nSeroprotection (defined as hSBA titer ≥1:8 for all but A22 which is ≥1:16) at 48 months (54 months for MenACWY -CRM) after last dose\nPfizer CT \n(NCT03135834) \n201710–25 years; \nACWY naïveA 58/71 26/41\nMenABCWY (2 \ndoses 6 months \napart)MenACWY -\nCRM (1 dose) + \nMenB -FHbp (2 \ndoses 6 months \napart) 81.7% (70.7 –89.9) 63.4% (46.9 –77.9) 1.29 (1.00 –1.67)\nC 44/71 16/42 62.0% (49.7 –73.2) 38.1 % (23.6 –54.4) 1.63 (1.06 –2.49)\nW 64/70 29/41 91.4% (82.3 –96.8) 70.7% (54.5 –83.9) 1.29 (1.05 –1.59)\nY 71/71 40/42 100.0% (94.9 –100.0) 95.2% (83.8 –99.4) 1.05 (0.98 –1.12)\n10–25 years; \nB naïveB (A22) 39/139 30/94 28.1% (20.8 –36.3) 31.9% (22.7 –42.3) 0.88 (0.59 –1.31)\nB (A56) 50/145 29/98 34.5% (26.8 –42.8) 29.6% (20.8 –39.7) 1.17 (0.80 –1.70)\nB (B24) 53/145 26/98 36.6% (28.7 –44.9) 26.5% (18.1 –36.4) 1.38 (0.93 –2.04)\nB (B44) 27/148 16/99 18.2% (12.4 –25.4) 16.2% (9.5 –24.9) 1.13 (0.64 –1.98)\n10–25 years; \nACWY \nprimedA 40/40 23/23 100.0% (91.2 –100.0) 100.0% (85.2 –100.0) 1.00 (1.00 –1.00)\nC 75/76 52/58 98.7% (92.9 –100.0) 89.7% (78.8 –96.1) 1.10 (1.01 –1.21)\nW 40/40 21/23 100.0% (91.2 –100.0) 91.3% (72.0 –98.9) 1.10 (0.97 –1.24)\nY 40/40 22/22 100.0% (91.2 –100.0) 100.0% (84.6 –100.0) 1.00 (1.00 –1.00)\nPersistent Immunity Key Findings, Continued\nAuthor, pub year Age Serogroupn/N \nMenABCWYn/N\ncomparisonIntervention \nvaccine Comparator \nvaccine% (95% CI) for \nintervention% (95% CI) for \ncomparator Effect estimate —RR (95% CI)\nSeroprotection (defined as hSBA titer ≥1:8) at 13 months (12 months for MenACWY -CRM) after last dose\nPfizer CT \n(NCT04440176), \n2020, and Pfizer CT \n(NCT03135834), 201711–14 years for \nNCT04440176 \nand 10 –25 years \nfor \nNCT03135834; \nboth groups \nACWY naiveA 102/126 42/59\n1 dose of \nMenABCWY1 dose of \nMenACWY -CRM81.0% (73.0 –87.4) 71.2% (57.9 –82.2) 1.14 (0.95 –1.37)\nC 92/127 32/62 72.4% (63.8 –80.0) 51.6% (38.6 –64.5) 1.40 (1.08 –1.83)\nW 125/128 52/62 97.7% (93.3 –99.5) 83.9% (72.3 –92.0) 1.16 (1.04 –1.30)\nY 122/126 61/62 96.8% (92.1 –99.1)98.4% (91.3 –\n100.0)0.98 (0.94 –1.03)\n70\nSerious Adverse Event Findings\n1Nine SAEs occurred in 7 patients: Salmonella gastroenteritis (1 patient), depression (1 patient), anxiety (1 patient), suicide attempt (1 patient), \npostural orthostatic tachycardia syndrome (1 patient), dyspnea (1 patient), head injury due to motor vehicle accident (1 pati ent), traumatic spinal \ncord injury (1 patient), depression with suicidal ideation (1 patient). None of the SAEs were deemed related to the vaccine by the study \ninvestigators. \n2Eight SAEs occurred in 6 patients: cyst (1 patient), tendon injury (1 patient), dyskinesia (1 patient), migraine with aura (1 patient), aggression (1 \npatient), conversion disorder (1 patient), suicidal ideation (2 patients). None of the SAEs were deemed related to the vaccine by the study \ninvestigators. 711\n2\nNon -Serious Adverse Event Findings\n72▪Additional findings related to non -serious adverse events\n– NCT04440163: Attention -deficit/hyperactivity disorder (ADHD) was reported by 6 participants in the MenABCWY group \nas newly diagnosed chronic medical conditions (NDCMC). Five had an onset of ADHD -related symptoms that occurred \nprior to study enrollment and the remaining participant had a history of one or more conditions prior to enrollment \nthat commonly co -occur with ADHD, including anxiety, depression, and substance use. Overall, none of the NDCMCs \nreported were considered related to vaccine by the investigators.\n– No other non-serious adverse events that we are aware of were disproportionately overrepresented in the \nMenABCWY group from any of the trials. \nNimenrix Background\n▪Nimenrix is not approved in the United States, but has been available in \nother parts of the world for about a decade\n▪The next few slides provide some background on the vaccine’s safety, \nimmunogenicity, and potential interference with other routinely \nadministered vaccines\n73\nNimenrix Safety\n▪First licensed in the European Union in April 2012\n▪Currently licensed in more than 80 countries worldwide\n▪More than 20 thousand people participated in Nimenrix clinical trials\n▪Over a decade of post -marketing safety data available\n–More than 30 million doses given worldwide\n–Safety consistent between CTs and post -marketing experience\n–Most common adverse events —fever, headache, injection site pain, nausea/vomiting, \nfatigue\n–Serious adverse events rare relative to doses given\n–Safety also consistent with other licensed meningococcal vaccines\n1Serra et al. Clinical trial and postmarketing safety experience with MenACWY -TT, a meningococcal group A, C, W, and Y tetanus c onjugate vaccine. \nVaccine . 2022; 40:7014 –7021. 74\nNimenrix Safety, Continued\n▪One clinical trial on MenACWY -TT and asplenia1\n–Phase III, non -randomized study\n–1 to 17 year olds with impaired splenic activity with age -matched healthy \ncontrols\n▪Results\n–Both study groups had high and comparable hSBA vaccine response rates \nacross serogroups\n•First dose: 55.6 –77.1% vs. 60.6 –76.3% \n•Second dose: 73.0 –100% vs. 73.0 –85.3% \n–SAEs were comparable (4/43 vs. 1/43) and none were deemed vaccine related\n•Cystitis due to Escherichia coli , pneumococcal bacteremia, salmonellosis, and sickle -\ncell anemia with crisis\n1Klein et al. Immunogenicity and safety of the quadrivalent meningococcal ACWY -tetanus toxoid conjugate vaccine (MenACWY -TT) in \nsplenectomized orhyposplenic children and adolescents: Results of a phase III, open, non -randomized study. Vaccine . 2018. 36;2356 –2363. 75\nNimenrix Persistence Compared to Menactra —5 Years After \nPrimary Vaccination in Young Adults Aged 11 –25 Years1\n1 Pfizer. Nimenrix Product Label. ShowLabeling.aspx (pfizer.com) . 050100150200250\nA C W YGMT\nSerogroupNimenrix\nMenactra\n76\nNimenrix Persistence Compared to MenQuadfi —3 Years After \nPrimary Vaccination in Children Aged 4 –5 Years1\n1 Sanofi Pasteur. Immunogenicity and Safety of an Investigational Quadrivalent Meningococcal Conjugate Vaccine Administered as a Booster Dose in Children \nVaccinated 3 Years Earlier as Toddlers. EU Clinical Trials Registry. https://www.clinicaltrialsregister.eu/ctr -search/trial/2017 -001993 -40/results . 020406080100120\nA C W YGMT\nSerogroupNimenrix\nMenQuadfi\n77\nOverall Certainty of Evidence —PICO 1 (Table 5)\nOutcome ImportanceIncluded in    \nEvidence ProfileCertainty for \nHealthy \nIndividualsCertainty for \nIndividuals at \nIncreased Risk\nMeningococcal disease caused by \nserogroups A, B, C, W, and YCritical No – –\nShort -term immunity Critical Yes Moderate Low\nPersistent immunity Important Yes Low Low\nInterference with other recommended \nvaccines administered concurrentlyImportant No – –\nSerious adverse events Critical Yes Low Very low\nNon -serious adverse events Important Yes Low Very low\n78\nOverall Certainty of Evidence —PICO 2 (Table 5)\nOutcome ImportanceIncluded in    \nEvidence ProfileCertainty for \nHealthy \nIndividualsCertainty for \nIndividuals at \nIncreased Risk\nMeningococcal disease caused by \nserogroups A, B, C, W, and YCritical No – –\nShort -term immunity Critical Yes Moderate Low\nPersistent immunity Important Yes Low Low\nInterference with other recommended \nvaccines administered concurrentlyImportant No – –\nSerious adverse events Critical Yes Low Very low\nNon -serious adverse events Important Yes Low Very low\n79\nOverall Certainty of Evidence —PICO 3 (Table 5)\nOutcome ImportanceIncluded in    \nEvidence ProfileCertainty for \nHealthy \nIndividualsCertainty for \nIndividuals at \nIncreased Risk\nMeningococcal disease caused by \nserogroups A, B, C, W, and YCritical No – –\nShort -term immunity Critical Yes Moderate Low\nPersistent immunity Important Yes Moderate Low\nInterference with other recommended \nvaccines administered concurrentlyImportant No – –\nSerious adverse events Critical Yes Low Very low\nNon -serious adverse events Important Yes Low Very low\n80\nEquity Considerations\nHISPANIC NON -HISPANIC NON -HISPANIC NON -HISPANIC\nWHITE ONLY BLACK ONLY OTHER + \nMULTIPLE\nRACE\n% 1+ dose MenB 31.83 30.88 39.67 24.73Among 17yos in NIS -Teen 2021:\n81\nEquity Considerations, Continued\n82\n83Equity Considerations, Continued\n▪Potential equity issues exist involving meningococcal vaccination more generally1\n–“Among adolescents aged 17 years, coverage with ≥2 MenACWY doses was 11.8 percentage \npoints lower for those living in non -MSAs than for those in MSA principal cities. Disparities \nbetween non -MSAs and MSA principal cities were statistically significant for adolescents living at \nor above the poverty level, but not for those living below the poverty level.”\n–“Hispanic or Latino (Hispanic) adolescents had lower coverage with ≥2 MenACWY doses (−10.8 \npercentage points).”\n–“Adolescents who were uninsured had lower coverage with ≥1 MenACWY dose.”\n1 Pingali et al. National Vaccination Coverage Among Adolescents Aged 13 –17 Years —National Immunization Survey -Teen, United States, 2021. \nMMWR . 2022. 71; 1101 –1108. \n84Demographic Information for NCT04440163\n\n85Routine and Increased Risk Vaccine Schedules for ≥10 Years Old\n▪Routine\n–One MenACWY dose at 11 –12 years and a booster at 16 years\n–Two MenB doses at 16 –18 years\n▪Increased risk, MenACWY (vaccines are interchangeable)\n–Recommended for certain medical conditions (asplenia, complement deficiency, complement inhibitor use, and HIV infection), \nsome microbiologists, exposure during an outbreak, travel to hyperendemic areas, first -year college students, and military \nrecruits\n–2 doses ≥8 weeks apart for primary vaccination (only 1 dose for microbiologists, travelers, military) and single booster dose\nevery 5 years thereafter for as long as person remains at increased risk\n–Only 1 dose during outbreaks if ≥5 years since MenACWY primary vaccination\n–Only 1 dose for first year college students within 5 years before starting college \n▪Increased risk, MenB (vaccines are not interchangeable)\n–Recommended for certain medical conditions (asplenia, complement deficiency, and complement inhibitor use), some \nmicrobiologists, and exposure during an outbreak\n–Bexsero: 2 doses ≥1 month apart followed by single dose 1 year later and every 2 –3 years thereafter for as long as person \nremains at increased risk\n–Trumenba: 3 doses at 0, 1 –2, and 6 months followed by single dose 1 year later and every 2 –3 years thereafter for period of \nincreased risk\n–Only 1 dose during outbreaks if ≥1 year after MenB primary series", "summary": "National Center for Immunization & Respiratory Diseases Evidence to Recommendations Framework: Pfizer’s MenABCWY Vaccine Sam Crowe, PhD, MPH Meningococcal Vaccines Work Group Lead June 23, 2023  Outline ▪Overview of policy questions and PICOs ▪Evidence to Recommendations framework ▪Summary of findings ▪WG proposed options 2 Pfizer MenABCWY Vaccine ▪Comprised of Trumenba (serogroup B) and Nimenrix (serogroups ACWY) –Trumenba •Consists of two purified recombinant lipidated FHbp antigens, one…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/03-Mening-Crowe-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 85}
{"title": "01 VaxSafety Shimabukuro 508", "content": "National Center for Emerging and Zoonotic Infectious Diseases\nVaccine safety updates\nAdvisory Committee on Immunization Practices (ACIP) meeting\nJune 23, 2023\nTom T. Shimabukuro, MD, MPH, MBA\nDirector, Immunization Safety Office\nDivision of Healthcare Quality Promotion \nCenters for Disease Control and Prevention (CDC)\n\nSession topics\n▪Background on the CDC Immunization Safety Office (ISO) and ISO \nefforts to evaluate studying the safety of the childhood \nimmunization schedule (Dr. Tom Shimabukuro)\n▪The childhood immunization schedule and safety: Studies in the \nVaccine Safety Datalink (Dr. Matthew Daley)\n▪Preliminary evaluation of aluminum content in childhood vaccines \nand risk of asthma in a Danish nationwide cohort (Dr. Anders Hviid)\n▪Discussion\n2\nCDC Immunization Safety Office (ISO) mission\n▪Monitor the safety of vaccines given to children and adults\nISO key activities\n▪Monitor newly recommended vaccines and new recommendations for existing vaccines\n▪Monitor CDC priority vaccines, including seasonal influenza and COVID -19 vaccines\n▪Conduct planned safety studies\n▪Support data needs of the Advisory Committee on Immunization Practices (ACIP)\n▪Assess individual risk factors for adverse events, conduct clinical case reviews, and provide \nclinical consultation to U.S. healthcare providers and health departments about vaccine safety \nquestions for individual patients  \n▪Respond to vaccine safety inquiries\n▪Conduct vaccine safety communication and education\n▪Coordinate with state health departments\n▪Prepare for pandemic and emergency responses3\n4\nVSD CISA\n5\n▪The lack of conclusive evidence linking adverse events to \nmultiple immunizations or other “schedule” exposures \nsuggests that the recommended schedule is safe.\n▪The risks to participants' health, the cost and time involved, \nand the ethical challenges all make the conduct of an \n[randomized controlled trial] RCT unsuitable for addressing \nthe research questions, at least until further work with \nsecondary data has been conducted.\n▪Although each new vaccine is evaluated in the context of the \noverall immunization schedule that existed at the time of \nreview of that vaccine, elements of the schedule are not \nevaluated once it is adjusted to accommodate a new \nvaccine. Thus, key elements of the entire schedule —the \nnumber, frequency, timing, order, and age at administration \nof vaccines —have not been systematically examined in \nresearch studies.\n▪The most feasible approach to studying the safety of the \nchildhood immunization schedule is through analyses of \ndata obtained by [the Vaccine Safety Datalink] VSD. Institute of Medicine. The Childhood Immunization Schedule and \nSafety: Stakeholder Concerns, Scientific Evidence, and Future \nStudies. Washington (DC): National Academies Press (US); 2013.2013\n6Four objectives of White Paper\n1.Define types of alternative immunization schedules \nand patterns of undervaccination that could be \nevaluated, focusing on the first 24 months of age\n2.Identify plausible adverse event outcomes that could \nbe related to the childhood immunization schedule, \nwith an emphasis on long -term adverse events\n3.Suggest methodological approaches that could be \nused to assess the safety of the recommended \nschedule as a whole\n4.Propose next steps for studying the safety of the \nchildhood immunization schedule within the VSD\nWhite Paper on Studying the Safety of the Childhood \nImmunization Schedule. For the Vaccine Safety Datalink (cdc.gov)2014\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the \nofficial position of the Centers for Disease Control and Prevention.\nPhoto credit: James Gathany \n(https://wwwn.cdc.gov/phil/\nDetails.aspx?pid=8876 )", "summary": "National Center for Emerging and Zoonotic Infectious Diseases Vaccine safety updates Advisory Committee on Immunization Practices (ACIP) meeting June 23, 2023 Tom T. Shimabukuro, MD, MPH, MBA Director, Immunization Safety Office Division of Healthcare Quality Promotion  Centers for Disease Control and Prevention (CDC)  Session topics ▪Background on the CDC Immunization Safety Office (ISO) and ISO  efforts to evaluate studying the safety of the childhood  immunization schedule (Dr. Tom…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/01-VaxSafety-Shimabukuro-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 7}
{"title": "02 VaxSafety Daley 508", "content": "The Childhood Immunization Schedule and \nSafety: Studies in the Vaccine Safety Datalink\nMatthew F. Daley MD\nAdvisory Committee on Immunization Practices, June 23, 2023\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\n•No conflicts of interest to disclose\n•The findings in this presentation are those of the speaker and do not \nnecessarily represent the official position of the Centers for Disease \nControl and PreventionDisclaimers\nSchedule and Safety 2\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\n•2013 Institute of Medicine* (IOM) Report\n•Feasibility work in Vaccine Safety Datalink (VSD)\n•Three published VSD studies\noAntigens and non -targeted infections\noSchedule and type 1 diabetes (T1DM)\noAluminum and asthma\n•Future investigations\n•Schedule and safety: broader contextOutline\n3 Schedule and Safety*Now referred to as The National Academies of Sciences, Engineering, and Medicine (NASEM)\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\n•Subtitle: Stakeholder Concerns, Scientific Evidence, and Future Studies\n•Existing evidence supported safety of schedule “as a whole”\n•Evidence gaps: each new vaccine added to existing schedule; safety studies \nusually of acute adverse events; long -term health outcomes less well studied \n•Committee conclusions:\noRandomized clinical trials not suitable approach to address research questions about \nschedule for ethical reasons\noObservational studies needed in existing surveillance systems (including in VSD)\noMethods for such studies complex; feasibility work needed\noDevelop metrics for exposure to schedule\noFocus on long -term outcomes: allergic, autoimmune, neurologicIOM: The Childhood Immunization Schedule and Safety\n4 Schedule and SafetyRef: Institute of Medicine, National Academies Press, 2013. DOI: 10.17226/13563.\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\n•VSD: collaboration between CDC and integrated healthcare \norganizations, conducts vaccine safety surveillance and research\n•White Paper objectives:\noExposure: define measures of vaccination schedule which could be \nevaluated, with focus on first 24 months of life\noOutcomes: identify plausible adverse events, with emphasis on long -term \nadverse events\noKey design considerations, analytic approaches\n•Potential outcomes prioritized based on feasibility, public health \nsignificance, and public concernWhite Paper on Studying Schedule in VSD:\nFeasibility, Study Design, Outcomes\n5 Schedule and SafetyRef: Glanz JM et al, Vaccine. 2016;34 Suppl 1:A1 -A29.\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\n•High priority outcomes included: allergic disorders (e.g., asthma), \nautoimmune disease (e.g.,T1DM), neurologic (e.g., epilepsy)\n•Some public concerns may have limited biologic plausibility\n•Attention to bias, unmeasured confounding\no\no\noMisclassification bias: survey parents of under -vaccinated children\nUse negative control outcomes (example: injuries)\nControl for differences in health care utilization\n•Plan for a long and complex process; any initial positive associations \nwill need studies to refute or replicate initial findingsWhite Paper, Additional Conclusions\n6 Schedule and SafetyRef: 1) Glanz JM et al, Vaccine. 2016;34 Suppl 1:A1 -A29. 2) Daley MF et al, Vaccine. 2017;35(15):1873 -1878. 3 ) Daley MF et al, Acad Pediatr . 2018;18:754 -762. \nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\n•Public concern: early childhood immunization “overloads” immune system\n•Design: Matched case -control\n•Exposures: cumulative vaccine antigen exposure, estimated by summing\nnumber of antigens in each vaccine dose birth through age 23 months\n•Outcomes:\noNon-vaccine -targeted infections in emergency department and inpatient settings\nfrom 24 through 47 months of age\noManual medical record review validation of sample of outcomes\n•Matching: age, sex, presence of chronic diseaseVSD Study: Antigens and Non -Targeted Infections\n7 Schedule and SafetyRef: Glanz MF et al, JAMA. 2018;319(9):906 -913.\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\n•Among children with versus without non -vaccine -targeted infections \nfrom 24 through 47 months of age, matched odds ratio for cumulative \nvaccine antigen exposure not significant:\noMatched odds ratio, 0.94; 95% CI, 0.84 to 1.07\n•Secondary analyses: consistent with primary findings\n•Conclusions:\noNo association between number of antigens young children receive through \nvaccines and likelihood of ED or inpatient encounters for infections\noNo evidence schedule “overwhelms” immune systemResults: Antigens and Non -Targeted Infections\n8 Schedule and SafetyRef: Glanz MF et al, JAMA. 2018;319(9):906 -913.\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\n•Public concern: vaccine antigens and ingredients (including aluminum, used as \nadjuvant) interfere with immune function, increase risk of autoimmune disease\n•Design: retrospective cohort\n•Exposures:\no\no\noCumulative vaccine antigen\nCumulative vaccine aluminum\nAverage days under -vaccinated\n•Outcome: T1DM, identified using diagnosis codes\n•Follow up: Mean length of follow up >5 years\n•Analyses adjusted for sex, race and ethnicity, maternal age, birth weight, \ngestational age, utilization (number of well -child visits)VSD Study: Schedule and Type 1 Diabetes\n9 Schedule and SafetyRef: Glanz MF et al, Pediatrics. 2021;148(6):e2021051910.\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\n•Main analyses, three different exposures:\noCumulative vaccine antigen non-significant : adjusted hazard ratio 0.98; 95% CI, 0.97 –1.00\noCumulative vaccine aluminum inversely associated : adjusted hazard ratio 0.77; 95% CI, 0.60 –0.99\noAverage days under -vaccinated non-significant : adjusted hazard ratio 1.01; 95% CI, 0.99 –1.02 \n•Sensitivity analyses, factoring in family history T1DM: similar to \nprimary results\n•Conclusions:\noVaccine schedule not associated with increased risk of T1DM\noDecreased risk at higher vaccine aluminum exposure: modest effect size; \nmore study needed to refute or replicate this findingResults: Schedule and Type 1 Diabetes\n10 Schedule and SafetyRef: Glanz MF et al, Pediatrics. 2021;148(6):e2021051910.\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\n•Public concern: vaccine ingredients (specifically aluminum, used as adjuvant) \nincrease risk of allergic disorders including asthma\n•Biologic plausibility: based on animal data, aluminum in vaccines could “skew” \ntoward T -helper cell 2 (Th2) response; Th2 cells play role in allergic asthma\n•Design: retrospective cohort\n•Exposure: cumulative vaccine aluminum received birth through 23 months of age\n•Outcome: persistent asthma at 24 through 59 months of age\noOne inpatient or two outpatient diagnoses of asthma PLUS\noOne or more prescriptions for a long -term asthma control medication\n•All analyses done separately for children with and without eczemaVSD Study: Aluminum and Asthma\n11 Schedule and SafetyRef: 1) Baylor NW et al, Vaccine. 2002;20 Suppl 3:S18 -23. 2) Goullé JP et al, Med Mal Infect. 2020;50:16 -21. 3) Hogenesch H. Front Immunol. 2012;3:406. 4) Sastry \nM et al, PLoS One. 2017;12:e0186854. 5) Alessandrini F et al, Front Immunol. 2020;11:575936. 6) Daley MF et al, Acad Pediatr . 2023 Jan -Feb;23(1):37 -46. \nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\n•N=14337 with eczema: 6.0% developed persistent asthma\n•N=312654 without eczema: 2.1% developed persistent asthma\n•Median vaccine -associated aluminum:\noEczema cohort=4.18 mg\noNo eczema cohort=4.18 mg\n12 Schedule and SafetyRef: Daley MF et al, Acad Pediatr . 2023 Jan -Feb;23(1):37 -46. Results: Aluminum and Asthma Study\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\nCrude \nIncidence Rate \nof Asthma by \nQuantity of \nVaccine-\nAssociated \nAluminum\n13\n Schedule and SafetyRef: Daley MF et al, Acad Pediatr . 2023 Jan -Feb;23(1):37 -46. \nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\nAssociation between Cumulative Vaccine -Associated \nAluminum and Persistent Asthma\nNotes: Cox proportional hazards analyses; separate models for eczema and no eczema cohorts; other covariates included number of outpatient visits; number of ED \nvisits; child’s race/ethnicity; medical complexity; VSD site; birth month and year. EGA, estimated gestational age.\n14 Schedule and Safety\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\nAluminum and Asthma Study: Secondary Analyses\nNotes: Cox proportional hazards analyses; separate models for eczema and no eczema cohorts; other covariates included number of outpatient visits; number of ED \nvisits; child’s race/ethnicity; medical complexity; VSD site; birth month and year\n15 Schedule and Safety\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\n•Small positive association between cumulative vaccine -associated aluminum \nbefore 24 months and persistent asthma 24 -59 months\n•Positive finding for children with and without eczema\n•Secondary analyses: positive associations in some but not all analyses\n•Study strengths: deliberate process; extensive feedback; large sample; VSD with \nhigh data quality; sophisticated analyses\n•Study limitations: no data on dietary/environmental aluminum exposure (although \nlittle to none of ingested aluminum absorbed per recent AAP report); no data on \nsocial determinants of health; unmeasured confounding; antigen effects\n•The first step of a multi -step research processInterpretation: Aluminum and Asthma Study\n16Ref: 1) Daley MF et al, Acad Pediatr . 2023 Jan -Feb;23(1):37 -46. 2) Corkins MR, AAP Committee on Nutrition. Pediatrics. 2019;144:e20193148.\nSchedule and Safety\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\nAsthma Prevalence among Children <18 years of Age:\nUnited States, 1980 –2020\n17 Schedule and Safety0.02.04.06.08.010.012.0\n1980 1982 1984 1986 1988 1990 1992 1994 1996 1998 2000 2002 2004 2006 2008 2010 2012 2014 2016 2018 2020\nYearPCV7DTaP \nreplaces DTPHib\nHep BHep A \n(high incidence)\nHep A \n(national)DTaP-Hep B-IPV\n(PediarixTM)DTaP-IPV-Hib\n(Pentacel ®)\nPCV13\nreplaces PCV7Percent \n(%)\nRef: The data from 1980 -1996 and 2001 -2020 are from National Health Interview Survey ( NHIS): 1) 1980 –1996 data are from Akinbami LJ, Schoendorf\nKC, Parker J. Am J Epidemiolol . 2003. 2) 2001 –2020 data are from https://www.cdc.gov/asthma/nhis/default.htm\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\n•Denmark national databases (Dr. Anders Hviid presentation at ACIP)\n•New study in VSD:\noCohort: larger cohort, longer follow up time\noExposure: aluminum before 12 months of age\noEczema: treat eczema as covariate\noOutcome: asthma diagnosed at a later age (60 through 84 months of age); \nasthma diagnosed earlier may represent viral -induced wheezing (not asthma)\n•Additional consideration of other data sources which could help \nassess relationship between vaccine aluminum exposure and \nsubsequent asthma riskFurther Investigations, Vaccine Aluminum and Risk of Asthma\n18 Schedule and Safety\nKAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH\n•Totality of available evidence continues to support the safety of the routine childhood \nvaccination schedule\n•Existing federal vaccine safety surveillance systems robust and responsive to concerns \nexpressed by parents of young children\n•Precipitated by 2013 IOM Report on schedule, new field of study is being developed:\noExamine cumulative, repeated exposures to vaccines and vaccine ingredients\noExamine long -term health outcomes\n•At time of IOM Report, few studies of the safety of the schedule “as a whole”\n•Evidence accumulating around specific testable hypotheses; results which can be \ncommunicated to parents\n•Additional studies related to aluminum and asthma risk planned and ongoing\n•Benefits of vaccination strongly outweigh known and potential risksThe Schedule and Safety: Broader Context\n19 Schedule and Safety\nTHANK YOU\n20", "summary": "The Childhood Immunization Schedule and  Safety: Studies in the Vaccine Safety Datalink Matthew F. Daley MD Advisory Committee on Immunization Practices, June 23, 2023 KAISER PERMANENTE INSTITUTE FOR HEALTH RESEARCH •No conflicts of interest to disclose •The findings in this presentation are those of the speaker and do not  necessarily represent the official position of the Centers for Disease  Control and PreventionDisclaimers Schedule and Safety 2 KAISER PERMANENTE INSTITUTE FOR HEALTH…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/02-VaxSafety-Daley-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 20}
{"title": "03 VaxSafety Hviid 508", "content": "Preliminary evaluation of aluminum content in childhood vaccines and risk of \nasthma in a Danish nationwide cohort\nProf. Anders Hviid, Statens Serum Institut, Copenhagen, Denmark\nAdvisory Committee on Immunization Practices, June 23, 2023  \n\nStudy cohort\n•Born in Denmark 2009 -2016\n•Study start 1/1 2011 ; study end 12/31 2018\n•Follow -up from 2 to 5 -years -of-age\n•Exposure and outcome data from nationwide -\nregisters\n•N=470,477 children\n2\nThe Danish schedule\n3Danish schedule\n3 mo.:   DiTePeIPVHib1 + PCV1\n5 mo.:   DiTePeIPVHib2 + PCV2\n12 mo.: DiTePeIPVHib3 + PCV3\n15 mo.: MMR1\n4 yrs:     MMR2\n5 yrs:     DiTePeIPV booster\n12 yrs:   HPV1 and HPV2\n\nCumulative aluminium exposure\n4\nAsthma outcome definitions\n•Hospital contacts, ICD-10 J45 (asthma), J46 (status asthmaticus) , in-and \noutpatients \n•Community anti -asthmatics prescriptions: Inhaled corticosteroids (n=2), short -\nacting beta -agonists (n=3), montelukast (n=2), long -acting beta -agonists (n=1)\n•Primary outcome:  Hospitalization and/or anti -asthma drug use\n•Exclusion criteria: Any prescriptions orhospitalizations before the age of 2.\n•Date of outcome: First among the above events\n5\nSecondary outcomes -latent class analysis\nInpt.           Outpt .           SABA ICS            LABA        MON  Cluster 1: ” Montelukast ” \n6.5%\nCluster 2: ”SABA”\n23.3%\nCluster 3: ” Hospitalization ”\n7.9%\nCluster 4: ” Inhaled corticosteroids +/-SABA”\n62.3%\n6SABA: Short-acting beta agonist; LABA: Long-acting beta agonist; ICS: Inhaled corticosteroid; MON: Montelukast.\nCohort characteristics\n7Cumulative aluminum received by 2-yrs- of-age\nKOEN: Sex; OPR: Mothers country of origin .\nMain Results –Hosp. or anti -asthma medication\nTable : Association between cumulative aluminum received through vaccines by age 2 and asthma by \nage 5 among 470477 Danish children born 2009 to 2016 and followed 2011 to 2018 \n Asthma cases1 Person -years of follow -up Hazard ratio (95% CIs)2 \n0 mg  62 13,082.00  0.90 (0.68 to 1.19)  \n<2.25mg  327 65,167.16  1.00 ( - to -) \n2.25mg  446 78,643.45  1.07 (0.92 to 1.24)  \n>2.25mg -<3.375mg  1092  206,053.42  1.00 (0.88 to 1.14)  \n3.375mg  3096  597,727.75  0.98 (0.86 to 1.11)  \n>3.375mg  838 165,528.63  1.00 (0.84 to 1.18)  \n1Hospitalization and/or anti -asthma prescription drug use  \n2Adjusted for sex, year of birth, maternal country of origin, and MMR vaccination by age 2.  \n \n8Aluminum\nMain Results –Dose -response\n9\nAssociation between aluminum and asthma clusters \n10Hazard Ratio* (95% CI)\n* Adjusted for sex, year of birth , maternal country of origin , MMR vaxbefore 2-yrs-of-age Comparing >3.375mg \ncumulative aluminum received\nthrough vaccines by 2-yrs- of-age \nto <2.25mg \nLimitations\n11•Limited variability in cumulative aluminum\n•Validity of using asthma diagnosis and anti -\nasthma drug use before 5 -yrs-of-age\nTake -away\n•No support for an association between \naluminium in vaccines and asthma by 5 -\nyrs-of-age in Denmark\n12", "summary": "Preliminary evaluation of aluminum content in childhood vaccines and risk of  asthma in a Danish nationwide cohort Prof. Anders Hviid, Statens Serum Institut, Copenhagen, Denmark Advisory Committee on Immunization Practices, June 23, 2023    Study cohort •Born in Denmark 2009 -2016 •Study start 1/1 2011 ; study end 12/31 2018 •Follow -up from 2 to 5 -years -of-age •Exposure and outcome data from nationwide - registers •N=470,477 children 2 The Danish schedule 3Danish schedule 3 mo.:  …", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/03-VaxSafety-Hviid-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 12}
{"title": "01 COVID Daley 508", "content": "cdc.gov/coronavirus\nACIP COVID -19 Vaccines Work Group\nDr. Matthew F. Daley, Work Group Chair\nJune 23, 2023\n▪COVID -19 vaccine program updates\n▪Vaccine safety updates\n▪Vaccine effectiveness data updates \n▪Data and Work Group considerations for updates to vaccine policy\n–Single bivalent vaccine dose for most persons aged ≥6 years \n–Bivalent vaccines for children aged 6 months –5 years\n–Optional additional bivalent doses for persons aged ≥6 months who are moderately or \nseverely immunocompromised and adults aged ≥65 years\n▪Clinical considerations updateApril ACIP COVID-19 Meeting Review\nApril 19, 2023\n2\n▪Epidemiology of COVID -19, including among pregnant people and infants\n▪Vaccine effectiveness (VE) updates\n▪Discussion of populations who still need a primary seriesACIP COVID-19 Work Group Meeting Review\nMay– June 2023\n3\n▪June 15, 2023: FDA’s Vaccines and Related Biological Products Advisory \nCommittee (VRBPAC) met to discuss strain selection for updated COVID -19 \nvaccines\n–Based on the totality of the evidence presented, FDA advised \nmanufacturers to develop updated COVID -19 vaccines with a monovalent \nXBB.1.5 composition\n–Anticipate updated vaccine doses will be broadly available in the fall \n–Following updated vaccine authorizations, ACIP will review evidence to \ninform updated recommendationsCOVID-19 vaccine update:\nVRBPAC Meeting\n4https://www.fda.gov/vaccines-blood-biologics/updated-covid- 19-vaccines-use-united-states-beginning-fall- 2023\nAgenda: \nFriday June 23, 2023\n•\n•\n•Updates to COVID-19 epidemiology and vaccine \neffectivenessDr. Havers (CDC)\nDr. Galang (CDC)\nDr. Link -Gelles (CDC)\nInfection-induced and hybrid immunity Dr. Jones (CDC)\nSummary and Work Group considerations Dr. Wallace (CDC)\nACIP members\n▪\n▪\n▪\n▪\n▪\n▪\n▪\n▪\n▪\n▪\n▪\n▪\n▪\n▪▪\n▪\n▪\n▪\n▪\n▪\n▪\n▪\n▪\n▪\n▪\n▪▪ Matthew Daley (chair)\nBeth Bell \nGrace Lee\nKeipp Talbot\nOliver Brooks\nEx-officio/government members\nFDA: Rachel Zhang, Lucia Lee, Anuja Rastogi\nNIH: Chris Roberts\nIHS: Uzo Chukwuma\nCMS: Jeff Kelman\nBARDA: Christine Oshansky\nHHS: Valerie Marshall\nCDC: Alan Lam\nCDC Leads\nSara Oliver\nMegan WallaceWork Group members\n6Liaisons\nAAFP: Jonathan Temte\nAAP: Sean O’Leary\nACOG: Denise Jamieson (primary), \nLaura Riley (alternate)\nACP: Jason Goldman\nADS: Emily Kahn\nAGS: Ken Schmader\nAIM: Rob Shechter (primary), \nJane Zucker (alternate)\nAMA: Sandra Fryhofer\nANA: Ruth Francis (alternate)\nAPhA: Michael Hogue\nASTHO: Marcus Plescia\nCSTE: Paul Cieslak, Christine Hahn\nIDSA: Jeff Duchin (primary)Liaisons, cont’d\nNACCHO: Matt Zahn (primary),\nJeff Duchin (alternate) \n▪NACI: Matthew Tunis (primary),\nNicole Forbes (alternate)\n▪NFID: Bill Schaffner (primary), \nMarla Dalton (alternate)\n▪NMA: Patricia Whitley-Williams\n▪SHEA: Preeti Mehrotra\nMarci Drees (alternate)  \nConsultants\n▪Ed Belongia\n▪Hank Bernstein\n▪Kathy Edwards\n▪Robert Hopkins\n▪Lisa Jackson\n▪Kathy Kinlaw\n▪Dayna Matthew ▪Jennifer Nelson\n▪Kathleen Neuzil\n▪Stanley Perlman\n▪Peter Szilagyi\n▪Sarah Meyer\n▪Elisha Hall\n▪Danielle Moulia\n▪Lauren Roper\n▪Hannah Rosenblum\n▪Katherine Fleming -Dutra\n▪Monica Godfrey\n▪Susan Goldstein\n▪Mary Chamberland\n▪Stephen Hadler\n▪JoEllen Wolicki\n▪Melinda Wharton\n▪Jessica MacNeil\n▪Amanda Cohn\n▪Ruth Link -GellesCDC participants\n7▪Amadea Britton\n▪Carolyn Bridges\n▪Allison Ciesla \n▪Nicole Dowling\n▪Ashley Fowlkes\n▪Heather Scobie\n▪Natalie Thornburg\n▪Tom Shimabukuro\n▪John Su\n▪Karen Broder\n▪Rita Helfand\n▪Jefferson Jones\n▪Yvonne Bolen\n▪Samuel Graitcer\n▪Lisa Grohskopf▪Laura Steinhardt\n▪Ryan Wiegand\n▪Patricia Yu\n▪Yon Yu▪Katherina Grusich\n▪Aaron Hall\n▪Terri Hyde\n▪Kristen Nordlund\n▪Sierra Scarbrough\n▪Andrew Kroger\n▪Lauri Markowitz\n▪Noelle -Angelique Molinari\n▪Michael McNeil\n▪Morgan Najdowski\n▪Ismael Ortega -Sanchez\n▪Pragna Patel\n▪Amanda Payne\n▪Georgina Peacock\n▪Jose Romero\nFor more information, contact CDC\n1-800-CDC-INFO (232-4636)\nTTY:  1- 888- 232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the \nofficial position of the Centers for Disease Control and Prevention.\nThank you!", "summary": "cdc.gov/coronavirus ACIP COVID -19 Vaccines Work Group Dr. Matthew F. Daley, Work Group Chair June 23, 2023 ▪COVID -19 vaccine program updates ▪Vaccine safety updates ▪Vaccine effectiveness data updates  ▪Data and Work Group considerations for updates to vaccine policy –Single bivalent vaccine dose for most persons aged ≥6 years  –Bivalent vaccines for children aged 6 months –5 years –Optional additional bivalent doses for persons aged ≥6 months who are moderately or  severely…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/01-COVID-Daley-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 8}
{"title": "02 COVID Havers Galang Link Gelles 508", "content": "cdc.gov/coronavirus\nEpidemiology of COVID -19-Associated Hospitalizations, \nincluding in Pregnant Persons and Infants\nFiona Havers, MD, MHS, FIDSA\nTeam Lead, RESP -NET Hospitalization Surveillance Team\nCommander, US Public Health Service\nCoronavirus and Other Respiratory Viruses Division\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nAdvisory Committee on Immunization Practices\nJune 23, 2023\nCOVID -19-associated hospitalizations\nCOVID -NET: March 2020 –June 2023\nCOVID -NET Hospitalizations\n▪>250 acute -care hospitals\n▪98 counties in 13 states\n▪~10% of U.S. population\n▪Positive SARS -CoV-2 within 14 days of or \nduring hospitalization\n▪Screening or clinician -driven testing\n▪Clinical data is from representative sample \nof COVID -NET patients\n3\nWeekly COVID -19-associated hospitalization rates —COVID -NET, 14 U.S. \nStates\nRates highest in ≥75 years, \nfollowed by infants <6 months and \nthose 65 –74 years020406080100120140March 1, 2020 –June 3, 2023\n0-<6 months 6 months-4 years 5-11 years 12-17 years\n18-49 years 50-64 years 65-74 years ≥ 75 years020406080100120140\n7-Jan 7-Feb 7-Mar 7-Apr 7-MayJanuary 1 –June 3, 2023\n4\nCOVID -19-associated hospitalization rates by race and ethnicity*  —\nCOVID -NET, 14 U.S. States, October 2022 –May 2023\n* Black, White, American Indian/Alaska Native and Asian/Pacific Islander people \nwere categorized as non -Hispanic; Hispanic people could be of any race. Cumulative hospitalization rates \nremain highest in American \nIndian/Alaska Native and Black \npersons050100150200250300Hospitalization Rate per 100,000Age adjusted cumulative rates \nOctober 2022 –May 2023\n0246810121416Rate per 100,000Age adjusted 3 -week moving average rate \nJanuary –May 2023\nHispanic American Indian/Alaska Native Asian/Pacific Islander Black White\n5\nCOVID -19-associated hospitalizations in \npregnant persons\nCOVID -NET: January 2021 –April 2023\nCOVID -19-associated hospitalizations among pregnant persons aged 15 –\n49 years —COVID -NET, 14 U.S. States, January 2021 –April 2023\nMost pregnant people \nhospitalized with a positive SARS -\nCoV-2 test had no respiratory \nsymptoms\n•363 of 1,651 (21%) had respiratory \nsymptoms recorded\n•Proportion without respiratory \nsymptoms increased from 73% to 82%\nAmong symptomatic patients, \nthe proportion with underlying \nmedical conditions increasedJanuary –\nNovember 2021\n(pre-Omicron)\nN (%)December 2021 –\nJune 2022\n(early Omicron)\nN (%)July 2022 –April \n2023\n(later Omicron)\nN (%)\nTotal number 184 99 80\nAge group\n15-24 years 45 (16) 38 (31) 22 (21)\n25-34 years 98 (60) 46 (54) 45 (59)\n35-49 years 41 (25) 15 (15) 13 (20)\nAny underlying \nmedical conditions72 (33) 32 (33) 46 (56)\nAny pregnancy -\nassociated \ncomplications*37 (20) 25 (31) 23 (29)Table 1. Characteristics of COVID -19-associated hospitalized pregnant \npatients (15 –49 years) with respiratory symptoms\n*Pregnancy -associated complications include hypertensive disorders of pregnancy, \ngestational diabetes, intrauterine growth restrictions, and pre -eclampsia. Note that \npercentages are weighted to account for sampling scheme.  7\nJanuary –\nNovember 2021\n(pre-Omicron)\nN (%)*December 2021 \n–June 2022\n(early Omicron)\nN (%)*July 2022 –April \n2023\n(later Omicron)\nN (%) *\nTotal Number 184 99 80\nInterventions\nHigh flow nasal \ncannula20  (12) 2 (2) 0 (0)\nBIPAP/CPAP 5 (2) 1 (1) 1 (3)\nMechanical \nventilation15 (7) 3 (2) 1 (2)\nVasopressor 26 (15) 3 (2) 3 (6)\nDialysis or RRT 1 (0.5) 1 (1) 0 (0)\nSevere outcomes\nICU admission 31 (17) 7 (6) 2 (4)\nIn-hospital death 0 (0) 1 (1) 0 (0)Interventions and outcomes among pregnant patients with respiratory \nsymptoms and a positive SARS -CoV-2 test\nThe p roportion \nrequiring ICU \nadmission and \nvasopressor support \ndecreased over time\n*Note that percentages are weighted to account for sampling scheme.  8\n0102030405060708090100\nUnvaccinated Primary\nseries onlyPrimary \nseries + ≥ 1 \nboosterUnvaccinated Primary\nseries onlyPrimary \nseries + ≥ 1 \nboosterUnvaccinated Primary\nseries onlyPrimary \nseries + ≥ 1 \nbooster\nJanuary-November 2021 (n=1,231) December 2021-June 2022 (n=279) July 2022-January 2023 (n=239)Weighted %\nRespiratory symptoms No COVID-19 symptoms recordedVaccination status among pregnant patients hospitalized with \nlaboratory -confirmed SARS -CoV-2 infection by symptom status, COVID -\nNET, January 2021 –April 2023\nMore asymptomatic \npregnant patients \nreceived boosters \ncompared with \nsymptomatic \npatients\nMost pregnant \npatients had not \nreceived booster \ndoses\n9\nCOVID -19-associated hospitalizations in \ninfants <6 months\nCOVID -NET: March 2020 –May 2023\nInfants <6 months old had similar COVID -19–associated \nhospitalization rates to adults aged 65 –74 years old\nSource: COVID -NET: https://www.cdc.gov/coronavirus/2019 -ncov/covid -data/covid -net/purpose -methods.html . Data March 1, 2020 through March 31, 2023. Pre -Delta: March 1, 2020 –\nJune 19, 2021; Delta: June 20 –December 18, 2021; Omicron BA.1: December 19, 2021 –March 19, 2022; Omicron BA.2: March 20 –June 18, 2022; Omicron BA.5 (J une 19, 2022 –June 3, 2023)Pre-Delta DeltaOmicron\nBA.1Omicron\nBA.2Omicron BA.5 and later\n11020406080100120140160Hospitalization rate per 100,000\n0-<6 months 6 months-4 years 5-11 years 12-17 years 65-74 years ≥ 75 years\nHospitalization rates in infants, children and adolescents \naged 6 months through <18 years\nSource: COVID -NET: https://www.cdc.gov/coronavirus/2019 -ncov/covid -data/covid -net/purpose -methods.html . Data March 1, 2020 through March 31, 2023. Pre -Delta: March 1, 2020 –June \n19, 2021; Delta: June 20 –December 18, 2021; Omicron BA.1: December 19, 2021 –March 19, 2022; Omicron BA.2: March 20 –June 18, 2022; Omicron BA.5 (J une 19, 2022 –May 27, 2023)Pre-Delta DeltaOmicron\nBA.1Omicron\nBA.2Omicron BA.5 and later\n02468101214161820\n3/7/2020\n4/7/2020\n5/7/2020\n6/7/2020\n7/7/2020\n8/7/2020\n9/7/2020\n10/7/2020\n11/7/2020\n12/7/2020\n1/7/2021\n2/7/2021\n3/7/2021\n4/7/2021\n5/7/2021\n6/7/2021\n7/7/2021\n8/7/2021\n9/7/2021\n10/7/2021\n11/7/2021\n12/7/2021\n1/7/2022\n2/7/2022\n3/7/2022\n4/7/2022\n5/7/2022\n6/7/2022\n7/7/2022\n8/7/2022\n9/7/2022\n10/7/2022\n11/7/2022\n12/7/2022\n1/7/2023\n2/7/2023\n3/7/2023\n4/7/2023\n5/7/2023Rate per 100,000\n6 months <2 years 2-4 years 5-11 years 12-17 years\n12\nOn average, 15% of hospitalized infants <6 months with \nCOVID -19 were identified during their birth hospitalization*\n*Birth hospitalization was defined as admission date within 1 day of birth. Source: COVID -NET: https://www.cdc.gov/coronavirus/2019 -ncov/covid -data/covid -net/purpose -methods.html . Data March 1, 2020 \nthrough March 31, 2023. Pre -Delta: March 1, 2020 –June 19, 2021; Delta: June 20 –December 18, 2021; Omicron BA.1: December 19, 2021 –March 19, 2022; Omicron BA.2: March 20 –June 18, 2022; Omicron \nBA.5 (June 19, 2022 –March 31, 2023) . 18 16 1620\n11\n0%10%20%30%40%50%60%70%80%90%100%\nPre-Delta Delta Omicron BA.1 Omicron BA.2 Omicron BA.5 and later\nBirth hospitalization Separate hospitalization\n13\n95% of infants <6 months old with a separate hospitalization \nhad COVID -19 symptoms during the Omicron BA.5 period\nSource: COVID -NET: https://www.cdc.gov/coronavirus/2019 -ncov/covid -data/covid -net/purpose -methods.html . Data March 1, 2020 through March 31, 2023. Pre -Delta: March 1, 2020 –June 19, \n2021; Delta: June 20 –December 18, 2021; Omicron BA.1: December 19, 2021 –March 19, 2022; Omicron BA.2: March 20 –June 18, 2022; Omicron BA.5 (J une 19, 2022 –March 31, 2023)93 94 94 97 95\n0%10%20%30%40%50%60%70%80%90%100%\nPre-Delta Delta Omicron BA.1 Omicron BA.2 Omicron BA.5 and\nlater\nSymptoms No symptoms\n14\n1 in 5 infants < 6 months old with COVID -19 were admitted to \nthe ICU (excluding birth hospitalizations)\nSource: COVID -NET: https://www.cdc.gov/coronavirus/2019 -ncov/covid -data/covid -net/purpose -methods.html . Data March 1, 2020 through March 31, 2023. Pre -Delta: March 1, 2020 –June \n19, 2021; Delta: June 20 –December 18, 2021; Omicron BA.1: December 19, 2021 –March 19, 2022; Omicron BA.2: March 20 –June 18, 2022; Omicron BA.5 (J une 19, 2022 –March 31, 2023)19%\n5%\n2% 2%\n0.3%18%\n14%\n4%5%\n0.0%24%\n15%\n8%\n3%\n1%21%\n14%\n5%4%\n2%20%\n19%\n3%6%\n0%\n0%5%10%15%20%25%30%\nICU admission High flow nasal cannula Invasive mechanical\nventilationBiPAP or CPAP use In-hospital deathWEIGHTED %  OF COVID -19-ASSOCIATED HOSPITALIZATIONSPre-delta\nDelta\nOmicron BA.1\nOmicron BA.2\nOmicron BA.5 and later\n15\n•General : Hospitalization rates decreased in all age groups\n•The age distribution of persons hospitalized with COVID -19 has shifted such that the highest \nrates are in adults aged ≥75 years followed by those 65 -74 years and infants ages <6 months\n•Pregnant persons: \n•Most pregnant persons hospitalized with a positive SARS -CoV-2 test had no symptoms \nrecorded at admission and were likely identified through screening on admission\n•Among those with respiratory symptoms, the proportion with underlying medical conditions \nhas increased and the proportion with severe outcomes has decreased\n•Most hospitalized pregnant persons with a positive SARS -CoV-2 test, regardless of symptoms \nor reason for testing, were not up to date with vaccinations\n•Infants <6 months : Hospitalization rates increased in the Omicron period \n•Most hospitalized with COVID -19-like symptoms \n•Excluding birth hospitalizations, 20% admitted to the ICU since June 2022Trends in COVID -19-associated hospitalizations –COVID -NET, March 2020 \n–May 2023\n16\nAcknowledgments\nCoronaviruses and Other Respiratory \nViruses Division (CORVD):\nRESP -NET Team (COVID -NET/RSV -NET):\n•Michael Whitaker\n•Kadam Patel\n•Christopher Taylor\n•Huong Pham\n•Onika Anglin\n•Jenny Milucky\n•Bhoomija Chatwani\n•Michael Melgar\n•Monica Patton\nMany others in CORVD….▪State, Local, and Territorial \nhealth Department partners\n▪RESP -NET partners\nThank you.\nCenters for Disease Control and Prevention\nCOVID -19 in pregnant people\nRomeo Galang, MD MPH\nEmergency Preparedness and Response Team\nField Support Branch\nDivision of Reproductive Health\nNational Center for Chronic Disease Prevention and Health Promotion\nDisease burden and risks to \nmaternal and infant health\nCOVID -19 in Pregnant People\n▪COVID -19 during pregnancy is associated with more severe maternal \nhealth outcomes\n▪COVID -19 during pregnancy is associated with adverse pregnancy \noutcomes (e.g., preterm birth, stillbirth)\n▪Adverse maternal, fetal, and infant outcomes differed according to the \ncirculating variant\nReported COVID -19 cases overall and among pregnant people in the US\n(National COVID -19 Case Surveillance Data; Jan 22, 2020 –May 3, 2023)\nTotal among \npregnant people: \n226,263 cases\n738 ICU admissions\n329 Deaths \n050001000015000200002500030000\nOverall Cases\nCases among \npregnant \npeoplePre-Delta Delta Omicron \nAmong people with COVID -19, pregnancy increased the risk for ICU \nadmission and invasive ventilation\n(Living Systematic Review with data from 1 Dec 2019 -27 Apr 2021)\nOutcomes # Studies# with event/# in group (%)\nOdds ratio (95% CI)\nPregnant with COVID -19Non -pregnant with \nCOVID -19\nAll cause mortality 11 242/122 222 (0.2) 5252/2 138 726 (0.2) 1.48 (0.62 to 3.49)\nICU admission 10 912/118 403 (0.8) 11 513/1 908 957 (0.6) 2.61 (1.84 to 3.71)\nInvasive ventilation 8 310/116 458 (0.3) 3607/1 772 716 (0.2) 2.41 (2.13 to 2.71)\nECMO 5 19/30 694 (0.1) 122/432 623 (0.0) 3.71 (0.71 to 19.41)\nARDS 4 22/197 (11.2) 45/418 (10.8) 1.19 (0.24 to 5.95)\nMajor organ failure 4 5/197 (2.5) 28/418 (6.7) 0.39 (0.15 to 1.04)\nAllotey, J  et al. Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta -\nanalysis. BMJ . 2020. Final version 7 -May 2022 https://doi.org/10.1136/bmj.m3320ECMO: extracorporeal membrane oxygenation; ARDS: Acute respiratory distress syndrome\nAmong pregnant people , COVID -19 increased the risk for adverse \nmaternal, fetal, and infant outcomes \n(Living Systematic Review with data from 1 Dec 2019 -27 Apr 2021)\nOutcomes # Studies# with event/# in group (%)\nOdds ratio (95% CI)Pregnant with COVID -19Pregnant without \nCOVID -19\nMaternal outcomes:\nAll cause mortality 21 47/11 362 (0.4) 37/411 126 (0.0) 6.09 (1.82 to 20.38)\nICU admission 21 447/12 957 (3.4) 1962/459 359 (0.4) 5.41 (3.59 to 8.14)\nPreterm birth <37 weeks 48 1306/12 076 (10.8) 26 068/436 964 (6.0) 1.57 (1.36 to 1.81)\nPerinatal outcomes:\nStillbirth 25 76/9338 (0.8) 1397/414 139 (0.3) 1.81 (1.38 to 2.37)\nNeonatal death 21 16/3153 (0.5) 28/9 263 (0.3) 2.35 (1.16 to 4.76)\nAdmission to neonatal unit 29 687/4072 (16.9) 6968/193 124 (3.6) 2.18 (1.46 to 3.26)\nFetal distress 6 131/1073 (12.2) 246/3933 (6.3) 2.22 (1.45 to 3.41)\nAllotey, J  et al. Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta -\nanalysis. BMJ . 2020. Final version 7 -May 2022 https://doi.org/10.1136/bmj.m3320\nPregnancy -related mortality increased rapidly in 2021 (pre -Omicron), \nconsistent with rising rates of COVID -19 associated mortality\nThoma , M. E., & Declercq , E. R. (2023). Changes in Pregnancy -Related Mortality Associated With the Coronavirus Disease 2019 (COVID -19) Pandemic in the U nited States. Obstetrics and gynecology ,141(5), \n911–917. https://doi.org/10.1097/AOG.0000000000005182\nHave risks evolved by COVID -19 variant?\nFigure 1. Maternal deaths and maternal deaths mentioning \nCOVID -19, by count, US 2020 -2022\nPre-delta Delta Omicron\nNote:  Data for 2020 -2021 are final and data for 2022 -2023. Death counts between 1 -9 are suppressed in accordance with NCHS conf identiality standards. Weeks with COVID -19 death counts 1 -9 are noted on the figure with \nblack and grey diagonal lines.\nSource: CDC, National Center for Health Statistics. National Vital Statistics System, Provisional Mortality on CDC WONDER Onl ineDatabase. Accessed at http://wonder.cdc.gov/mcd -icd10 -provisional.html  020406080100120140160180200Number of Deaths\nDate of DeathMaternal Deaths without COVID-19 Maternal Deaths with COVID-19 Counts 1-9\nUpdated Premier: Pregnant Person Complications Associated With a \nDocumented COVID -19 Diagnosis at Delivery Hospitalization —\nUnited States, Pre -delta, Delta, and Omicron\nKo et al., 2021 (n = 489471)\nJune 2021 -December 2021 (n=505108 )\n2022 (n = 782503)\n*Data from Delta and \nOmicron periods are \nunpublished\n\nUpdated Premier: Pregnant Person Complications Associated With a \nDocumented COVID -19 Diagnosis at Delivery Hospitalization —\nUnited States, Pre -delta, Delta, and Omicron\nKo et al., 2021 (n = 489471)\nJune 2021 -December 2021 (n=505108 )\n2022 (n = 782503)Although less than Delta, \nrisks remain elevated \nduring Omicron\n*Data from Delta and \nOmicron periods are \nunpublished\nUpdated Premier: Pregnant Person Complications Associated With a \nDocumented COVID -19 Diagnosis at Delivery Hospitalization —\nUnited States, Pre -delta, Delta, and Omicron\n*Data from Delta and \nOmicron periods are \nunpublished\nKo et al., 2021 (n = 489471)\nJune 2021 -December 2021 (n=505108 )\n2022 (n = 782503)\nUpdated Premier: Pregnant Person Complications Associated With a \nDocumented COVID -19 Diagnosis at Delivery Hospitalization —\nUnited States, Pre -delta, Delta, and Omicron\nKo et al., 2021 (n = 489471)\nJune 2021 -December 2021 (n=505108 )\n2022 (n = 782503)\n*Data from Delta and \nOmicron periods are \nunpublishedSimilar pattern: Although less than Delta, \nincreased risks persisted during Omicron\nUpdated Premier: Pregnant Person Complications Associated With a \nDocumented COVID -19 Diagnosis at Delivery Hospitalization —\nUnited States, Pre -delta, Delta, and Omicron\nKo et al., 2021 (n = 489471)\nJune 2021 -December 2021 (n=505108 )\n2022 (n = 782503)\n*Data from Delta and \nOmicron periods are \nunpublished\nSimilar pattern: Although less than Delta, \nincreased risks persisted during Omicron\nAdverse Pregnancy Outcomes Associated With a Documented COVID -\n19 Diagnosis at Delivery Hospitalization —United States, \nPre-delta, Delta, and Omicron Periods, Premier\nKo et al., 2021 (n = 489471)\nJune 2021 -December 2021 (n=505108)\n2022 (n = 782503)\n*Data from Delta and \nOmicron periods are \nunpublished\n\nAdverse Pregnancy Outcomes Associated With a Documented COVID -\n19 Diagnosis at Delivery Hospitalization —United States, \nPre-delta, Delta, and Omicron Periods, Premier\nKo et al., 2021 (n = 489471)\nJune 2021 -December 2021 (n=509265)\n2022 (n = 765425)\n*Data from Delta and \nOmicron periods are \nunpublished•Although less than Delta, risks \nfor adverse pregnancy \noutcomes and preterm delivery \nremain elevated during Omicron\n•Risk for stillbirth not \nsignificantly elevated during \nOmicron\nTrends (%) in pregnancy outcomes by maternal COVID -19 status: \n14 states and the District of Columbia (July 2020 -December 2022)\npre-Delta\nJuly 2020 -June 2021Delta\nJuly 2021 -December 2021Omicron\nJanuary 2022 -December 2022\nCOVID -191No COVID -19 COVID -191No COVID -19 COVID -191No COVID -19\nICU admission 0.6 0.1 1.2 0.2 0.2 0.2\nNICU admission 10.3 8.7 10.9 8.5 9.0 8.7\nTotal preterm211.9 9.9 13.0 10.1 10.3 10.1\nEarly preterm 3.2 2.6 3.8 2.7 2.4 2.7\nLate preterm 8.8 7.2 9.2 7.4 7.9 7.4\nTotal low birthweight38.8 7.9 9.8 8.1 7.9 8.2\nVery low birthweight41.5 1.3 1.6 1.3 1.1 1.3\n1 Confirmed or presumed COVID -19 during pregnancy. Confirmed cases only are included for California, Maryland, Ohio, North Dakota, and Tennessee.\n2Gestational age in completed weeks; based on the obstetric estimate of gestation.\n3 Less than 2,500 grams\n4 Less than 1,500 grams\nNOTES: Reporting area includes Alabama, Alaska, Arkansas, California, District of Columbia, Idaho, Maine, Maryland, New Hamps hire, North Dakota, Ohio, Oklahoma, Oregon, Tennessee, and West Virginia. District of Columbia did not report for October -December \n2022.\nSOURCE: National Center for Health Statistics, National Vital Statistics System, Natality.\nhttps://www.cdc.gov/nchs/data/health_policy/trends -in-outcomes.pdf\nSummary\n▪Incidence of COVID -19 among pregnant people mirrors that of the general \npopulation\n▪Pregnancy remains a risk factor for severe maternal disease and adverse \npregnancy outcomes, even with new variants\n▪Some maternal, fetal, and infant risks were lower with Omicron; cannot \ndisentangle the impact of prior infection/vaccination\nConclusion\nCOVID -19 vaccination improves outcomes for pregnant \npeople, their pregnancies and their infants; therefore \nvaccination should continue to be recommended for maternal \nand fetal benefit\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the \nofficial position of the Centers for Disease Control and Prevention.\nNational Center for Immunization and Respiratory Diseases\nSascha Ellington\nKatherine Fleming -Dutra\nSara Oliver\nRegina Simeone\nNational Center for Health Statistics\nDonna Hoyert\nJoyce Martin\nMichelle Osterman\nClaudia ValenzuelaAcknowledgements\nNational Center on Birth Defects and Developmental Disorders\nJeffrey Carlson\nAmanda Cohn\nDana Meaney -Delman\nSuzanne Gilboa\nKara Polen\nEmily Reeves\nVan Tong\nKate Woodworth\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.COVID -19 vaccine effectiveness updates\n23 June 2023\nRuth Link -Gelles, PhD, MPH\nLCDR, US Public Health Service\nCOVID -19 Vaccine Effectiveness Program Lead\nCenters for Disease Control and Prevention\nCoverage / Age (years) <22–45–1112–1718–2424–4950–64>65\nAt least one dos e† 8.9 10.9 40.0 72.2 82.3 85.5 95.0 95.0\nAt least one bivalent dose 0.6 0.6 4.8 7.8 7.4 12.1 21.7 43.3\nUnvaccinated 91.1 89.1 60.0 27.8 17.7 14.5 —†—†U.S. COVID -19 Vaccination Coverage (%) of Total Population by \nAge Group —May 10, 2023\n†Note: Coverage is capped at 95%\nSource: https://covid.cdc.gov/covid -data -tracker/#vaccination -demographics -trends Updated June 1, 2023 39\n▪Bivalent VE, by outcome and Omicron subvariant in adults\n▪VE in special populations:\n–Monovalent and bivalent VE in pregnant people\n–Bivalent people with immunocompromising conditionsOrganization of vaccine effectiveness (VE) data\n40\nMonovalent and bivalent VE, against \nhospitalization and critical illness by Omicron \nsubvariant in adults ≥18 years, VISION Network\nVISION Multi -State Network of Electronic Health Records\n▪Variant periods designated for analysis \nbased on time when novel sublineage \nbecame predominant (>50%) at study \nsite\n▪VE a djusted for age, sex, race and \nethnicity, geographic region, and \ncalendar time\n▪Vaccination documented by electronic \nhealth records and state and city \nregistries▪Cases : COVID -like illness (CLI) with positive PCR for \nSARS -CoV-2 within 14 days before or 72 hours after the \nadmission or encounter\n▪Controls : CLI with negative PCR for SARS -CoV-2\n42\nVISION: Absolute VE of monovalent and bivalent booster doses against \nhospitalization and critical illness among immuno competent adults aged \n≥18 years –September 2022 –May 2023\nCritical illness defined as admission to intensive care unit or death; case -patients were persons admitted to ICU or who experie nced death associated with COVID -19, and control patients were persons hospitalized without COVID -19. \nVE estimates adjusted for age, sex, race and ethnicity, geographic region, and calendar time. Updated from: Link -Gelles et al., MMWR, https://www.cdc.gov/mmwr/volumes/72/wr/mm7221a3.htm43mRNA Dosage PatternTotal\ntestsSARS -CoV-2-\ntest-positive,\nN (%)Median interval\nsince last dose,\ndays (IQR)Adjusted VE\n(95% CI)\nHospitalization\nUnvaccinated (ref) 16,219 1,835 (11) -- Ref\nMonovalent doses only 38,843 4,086 (11) 381 (275 -513) 21 (16 -26)\nBivalent booster, 7 -59 days earlier 4,894 329 (7) 35 (21 -47) 62 (57 -67)\nBivalent booster, 60 -119 days earlier 5,283 491 (9) 87 (73 -103) 47 (41 -53)\nBivalent booster, 120 -179 days earlier 3,756 346 (9) 146 (132 -161) 24 (12 -33)\nCritical illness\nUnvaccinated (ref) 14,762 378 (3) -- Ref\nMonovalent doses only 35,415 658 (2) 380 (275 -514) 31 (21 -40)\nBivalent booster, 7 -59 days earlier 4,614 49 (1) 34 (21 -47) 69 (58 -77)\nBivalent booster, 60 -119 days earlier 4,880 88 (2) 87 (73 -103) 45 (29 -58)\nBivalent booster, 120 -179 days earlier 3,445 35 (1) 146 (132 -161) 52 (30 -67)\n-20 0 20 40 60 80 100\nVaccine Effectiveness (%)\nVISION: Absolute VE of monovalent and bivalent booster doses against \nhospitalization and critical illness among immuno competent adults aged ≥18 years, \nduring BA.4/5 predominance –September 2022 –January 2023\nCDC unpublished data. VE estimates adjusted for age, sex, race and ethnicity, geographic region, and calendar time.\nVariant predominance based on regional circulation: https://covid.cdc.gov/covid -data -tracker/#variant -proportions44mRNA Dosage PatternTotal\ntestsSARS -CoV-2-\ntest-positive,\nN (%)Median interval\nsince last dose,\ndays (IQR)Adjusted VE\n(95% CI)\nHospitalization\nUnvaccinated (ref) 11,240 1,426 (13) -- Ref\nMonovalent doses only 27,564 3,106 (11) 349 (238 -460) 25 (19 -30)\nBivalent booster, 7 -89 days earlier 6,723 524 (8) 47 (28 -67) 61 (56 -65)\nBivalent booster, ≥90 days earlier 1,511 163 (11) 105 (96 -115) 40 (28 -50)\nCritical illness\nUnvaccinated (ref) 10,110 296 (3) -- Ref\nMonovalent doses only 24,976 518 (2) 347 (236 -460) 33 (21 -42)\nBivalent booster, 7 -89 days earlier 6,199 91 (1) 47 (28 -66) 61 (50 -70)\nBivalent booster, ≥90 days earlier 1,348 25 (2) 105 (96 -115) 49 (21 -67)\n-20 0 20 40 60 80 100\nVaccine Effectiveness (%)\nVISION: Absolute VE of monovalent and bivalent booster doses against \nhospitalization and critical illness among immuno competent adults aged \n≥18 years, during XBB predominance –January –May 2023\nCDC unpublished data. VE estimates adjusted for age, sex, race and ethnicity, geographic region, and calendar time.\n* These interim estimates are imprecise, which might be because of a relatively small number of persons in each level of vacc ination or case status. This imprecision indicates \nthe actual VE may be substantially different from the point estimate shown, and estimates should therefore be interpreted wit h caution. Additional data accrual should increase \nprecision and allow appropriate interpretation.\nVariant predominance based on regional circulation: https://covid.cdc.gov/covid -data -tracker/#variant -proportions45mRNA Dosage PatternTotal\ntestsSARS -CoV-2-\ntest-positive,\nN (%)Median interval\nsince last dose,\ndays (IQR)Adjusted VE\n(95% CI)\nHospitalization\nUnvaccinated (ref) 4,979 409 (8) -- Ref\nMonovalent doses only 11,279 980 (9) 469 (375 -605) 9 (-4 to 20)\nBivalent booster, 7 -89 days earlier 1,045 60 (6) 65 (43 -79) 51 (35 to 63)\nBivalent booster, 90 -179 days earlier 4,654 419 (9) 139 (119 -157) 20 (7 to 32)\nCritical illness\nUnvaccinated (ref) 4,652 82 (2) -- Ref\nMonovalent doses only 10,439 140 (1) 469 (375 -602) 28 (3 to 46)\nBivalent booster, 7 -89 days earlier 994 9 (1) 65 (43 -78) 58 (15 to 79)*\nBivalent booster, 90 -179 days earlier 4282 47 (1) 139 (119 -157) 48 (23 to 65)\n-20 0 20 40 60 80 100\nVaccine Effectiveness (%)\nMonovalent and bivalent VE against \nhospitalization among adults aged ≥18 years , \nIVY Network\nIVY Network —25 hospitals, 20 U.S. States\n▪Design : Prospective, case -control\n▪Population : Adults aged ≥18 years hospitalized with \nAcute respiratory illness (ARI)*\n–Cases: ARI and test positive for SARS -CoV-2 by NAAT or \nantigen test within 10 days of illness\n–Controls: ARI and test negative for SARS -CoV-2 and influenza \nby NAAT within 10 days of illness\n▪Vaccination data: Electronic medical records (EMR), \nstate and city registries, and self -report\n▪Specimens: Upper respiratory specimens obtained \nfor central RT -qPCR testing and sequencing\n*ARI is defined as presence of any one of the following: fever, cough, shortness of breath, chest imaging consistent with pne umo nia, hypoxemia\nIVY Network: Absolute VE against COVID -19 hospitalization\namong immuno competent adults aged ≥18 years —September 8, \n2022 –May 29, 2023\nTotal Cases and \nControls Cases (%)Median time\nsince last dose,\ndays (IQR)Adjusted VE*,\n% (95% CI)\nAbsolute VE\nUnvaccinated (Ref) 1286 537 (42) -- Ref\nMonovalent doses only 3511 1460 (42) 393 (282 –517) 16 (3 to 26)\nBivalent booster dose, 7 –59 days earlier 374 100 (27) 36 (21–49) 54 (39 to 65)\nBivalent booster dose, 60 –119 days earlier 443 160 (36) 89 (73–103) 34 (15 to 50) \nBivalent booster dose, 120 –179 days earlier 366 157 (43) 145 (133 –159) 6 (-27 to 30)*\n-40 -20 0 20 40 60 80 100\nVaccine Effectiveness (%)\n* These interim estimates are imprecise, which might be because of a relatively small number of persons in each level of vacc ination or case status. This imprecision indicates the actual VE may be substantially different \nfrom the point estimate shown, and estimates should therefore be interpreted with caution. Additional data accrual should inc rease precision and allow appropriate interpretation.\nVE adjustments: Age, sex, race, ethnicity, admission date (biweekly), and HHS region\nIVY Network: Absolute VE against COVID -19 hospitalization\namong immuno competent adults aged ≥18 years by lineage \nperiod —September 8, 2022 –May 24, 2023\nTotal Cases and \nControls Cases (%)Median time\nsince last dose,\ndays (IQR)Adjusted VE*,\n% (95% CI)\nBA.4/5 (September 8 –November 13, 2022)\nUnvaccinated (Ref) 313 138 (44) -- Ref\nMonovalent doses only 1003 398 (40) 304 (188 –386) 30 (8–47)\nBivalent booster dose, 7 –59 days earlier 83 26 (31) 25 (13–40) 59 (21–78)*\nBQ.1 (November 14, 2022 –January 22, 2023)\nUnvaccinated (Ref) 458 190 (41) -- Ref\nMonovalent doses only 1262 504 (40) 386 (297 –518) 17 (-5 to 34)\nBivalent booster dose, 7 –59 days earlier 226 52 (23) 40 (25–52) 63 (44–75)\nBivalent booster dose, 60 –119 days earlier 225 68 (30) 83 (69–95) 49 (24–66)\nXBB (January 23 –May 24, 2023) \nUnvaccinated (Ref) 514 209 (41) -- Ref\nMonovalent doses only 1246 558 (45) 464 (378 –590) -8 (-34 to 13)\nBivalent booster dose, 7 –89 days earlier 155 56 (36) 64 (46–78) 29 (-8 to 53)*\nBivalent booster dose, 90 –179 days earlier 478 208 (44) 137 (118 –154) -8 (-44 to 19)*\n* These interim estimates are imprecise, which might be because of a relatively small number of persons in each level of vacc ination or case status. This imprecision indicates the actual VE may be\nsubstantially different from the point estimate shown, and estimates should therefore be interpreted with caution. Additional data accrual should increase precision and allow appropriate interpretation.\nVE adjustments: Age, sex, race, ethnicity, admission date (biweekly), and HHS region-55 -35 -15 5 25 45 65 85\nVaccine Effectiveness (%)\nVE in special populations:\npregnant people\nVISION Multi -State Network of Electronic Health Records\n▪Cases : COVID -like illness (CLI) with positive PCR for \nSARS -CoV-2 within 14 days before or 72 hours after the \nencounter\n▪Controls : CLI with negative PCR for SARS -CoV-2\n51▪Among pregnant people 18 -45 years at time of \nemergency department/urgent care encounter\n▪VE adjusted for age, ethnicity, race, underlying \nmedical conditions, gestational age at \nencounter, site, Medicaid status, day of \nencounter, site facility urbanicity\n▪Vaccination documented by electronic health \nrecords and state and city registries\n▪Separate results for COVID -19 vaccine \nmonovalent doses received prior to pregnancy \nand bivalent doses received during pregnancy \ndue to timing of bivalent authorization/analysis \n(Sept 2022 -May 2023)\nVISION: Absolute VE of COVID -19 monovalent doses received prior to\npregnancy against ED/UC encounters among immuno competent pregnant \npersons aged 18 -45 years –June 2022 –May 2023*\nAdjusted for: Age, ethnicity, race, underlying medical conditions, gestational age at encounter, site, Medicaid status, day o f encounter, site facility urbanicity\n*Unpublished CDC data.52Vaccine Dosage PatternTotal\ntestsSARS -CoV-2-\ntest-positive,\nN (%)Median interval\nsince last dose,\ndays (IQR)Adjusted VE\n(95% CI)\nAbsolute VE\nUnvaccinated (ref) 2238 317 (14) -- Ref\nMonovalent received:\n<6 months before pregnancy 833 108 (13) 270 (216, 326) 27 (6, 44)\n≥6 months before pregnancy 1986 264 (13) 454 (375, 544) 5 (-15, 22)\n-20 0 20 40 60 80 100\nVaccine Effectiveness (%)\nVISION: Absolute VE of COVID -19 bivalent doses received during pregnancy \nagainst ED/UC encounters among immuno competent pregnant persons aged \n18-45 years –September 2022 –May 2023*\nAdjusted for: Age, ethnicity, race, underlying medical conditions, gestational age at encounter, site, Medicaid status, day o f encounter, site facility urbanicity\n*Unpublished CDC data\n**Doses received during pregnancy for bivalent group\n***These interim estimates are imprecise, which might be because of a relatively small number of persons in each level of vac cination or case status. This imprecision \nindicates the actual VE may be substantially different from the point estimate shown, and estimates should therefore be inter preted with caution. Additional data accrual \nshould increase precision and allow appropriate interpretation.53Vaccine Dosage PatternTotal\ntestsSARS -CoV-2-\ntest-positive,\nN (%)Median \ninterval\nsince last dose,\ndays (IQR)Adjusted VE\n(95% CI)\nAbsolute VE\nUnvaccinated (ref) 1701 196 (12) -- Ref\nBivalent dose** 191 10 (5) 56 (29, 97) 61 (22, 81)***\n0 20 40 60 80 100\nVaccine Effectiveness (%)\n▪Cases infants : hospitalized with COVID -19 as the \nprimary reason for admission and with a positive \nSARS -CoV-2 RT -PCR or antigen test result\n▪Control infants : hospitalized with or without \nCOVID -19 symptoms and negative SARS -CoV-2 \nRT-PCR or antigen test result\n–Matched to case -infants by site; hospitalized within 4 \nweeks of case -infant admission▪Case -control study to assess effectiveness of \nmaternal vaccination for COVID -19 in infants < 6 \nmonths of age\n▪25 pediatric hospitals across 20 states\n▪Infants admitted between March 9, 2022, and \nMay 9, 2023\n▪Baseline demographic and clinical characteristics \nobtained via parent interview\n▪Maternal vaccination status verified using state \nvaccination registries, electronic medical records, \nor other sourcesOvercoming COVID -19 network\n54\n\nOvercoming COVID -19: Effectiveness of maternal vaccination in prevention \nof hospitalization among infants –March 9, 2022 –May 9, 2023\nCDC unpublished data. VE estimates adjusted for infant age, sex, race and ethnicity, census region, and month and year of hos pitalization. 55Vaccination during pregnancy* TotalCase infants,\nN (%)Median interval \nsince last maternal \ndose, days (IQR)Infant median age at \nhospitalization, days \n(IQR)Adjusted VE\n(95% CI)Effectiveness of Maternal Vaccination against \nInfant Covid -19 Hospitalization % (95% CI)†\nInfants <3 months of age at hospitalization\nUnvaccinated (ref) 310 174 (56) NA 44 (27 to 63) Ref\nVaccinated 101 43 (43) 222 (152 to 271) 41 (23 to 66) 56 (24 to 75)*\nInfants < 6 months of age at hospitalization\nUnvaccinated (ref) 498 281 (56) NA 68 (37 to 125) Ref\nVaccinated 163 78 (48) 236 (190 to 302) 74 (33 to 132) 38 (7 to 59)*\n0 20 40 60 80 100\nVaccine Effectiveness (%) \n*Last mRNA or viral vector vaccine dose received between the beginning of pregnancy and 14 days before delivery. 14 people re ceived a bivalent mRNA vaccine.\n†These estimates are imprecise, which might be because of a relatively small number of persons in each level of vaccination o r case status. This imprecision indicates the actual VE may be \nsubstantially different from the point estimate shown, and estimates should therefore be interpreted with caution. Additional data accrual should increase precision and allow appropriate \ninterpretation.\nBivalent VE in special populations:\npeople with immunocompromising conditions\nVISION: Absolute VE of monovalent and bivalent booster doses against \nhospitalization and critical illness among immuno compromised adults \naged ≥18 years –September 2022 –May 2023\n* These interim estimates are imprecise, which might be because of a relatively small number of persons in each level of vacc ination or case status. This imprecision indicates \nthe actual VE may be substantially different from the point estimate shown, and estimates should therefore be interpreted wit h caution. Additional data accrual should increase \nprecision and allow appropriate interpretation.\nCritical illness defined as admission to intensive care unit or death; case -patients were persons admitted to an ICU or who expe rienced death associated with COVID -19, and control patients were persons hospitalized\nwithout COVID -19. VE estimates adjusted for age, sex, race and ethnicity, geographic region, and calendar time. Updated from: Li nk-Gelles et al., MMWR, https://www.cdc.gov/mmwr/volumes/72/wr/mm7221a3.htm57mRNA Dosage PatternTotal\ntestsSARS -CoV-2-\ntest-positive,\nN (%)Median interval\nsince last dose,\ndays (IQR)Adjusted VE\n(95% CI)\nHospitalization\nUnvaccinated (ref) 3,240 322 (10) -- Ref\nMonovalent doses only 11,623 1,169 (10) 359 (242 -481) 3 (-12-16)\nBivalent booster, 7 -59 days earlier 1,627 144 (9) 33 (19 -46) 27 (9 -41)\nBivalent booster, 60 -119 days earlier 1,862 144 (8) 88 (74 -104) 39 (24 -51)\nBivalent booster, 120 -179 days earlier 1,448 118 (8) 146 (133 -161) 11 (-13-31)\nCritical illness\nUnvaccinated (ref) 3,006 88 (3) -- Ref\nMonovalent doses only 10,725 271 (3) 358 (241 -481) 16 (-10-35)\nBivalent booster, 7 -59 days earlier 1,515 32 (2) 33 (19 -46) 41 (8 -62)*\nBivalent booster, 60 -119 days earlier 1,755 37 (2) 88 (74 -104) 43 (13 -62)\nBivalent booster, 120 -179 days earlier 1,348 18 (1) 146 (133 -162) 51 (15 -72)*\n-20 0 20 40 60 80 100\nVaccine Effectiveness (%)\nSummary and conclusions\n▪For estimates of absolute vaccine effectiveness, if unvaccinated are meaningfully \ndifferent from vaccinated individuals (e.g., by COVID -19 risk factors), estimates may \nbe biased.\n–For estimates of relative vaccine effectiveness, residual protection from prior doses is an important \nconsideration for interpretation.\n▪Information on prior infection is limited, although we know rates of prior infection in \nthe U.S. population are high and vary by age. \n▪VE against COVID -19-associated hospitalization may underestimate protection against \nmore severe COVID -19 disease.\n▪Lack of statistical power to estimate VE for maternal vaccination by timing of doses \nduring pregnancy; could not separate monovalent and bivalent doses for protection \nagainst infant hospitalizationLimitations of VE against severe disease\n59\n▪Bivalent boosters are helping provide additional protection against hospitalization, though evidence of waning\n▪For most people who received monovalent doses and are eligible for a bivalent booster, more than a year has \nelapsed since their last monovalent dose. Because of waning, they may have limited remaining protection against \nhospitalization.\n▪Effectiveness against the most critical illness (ICU admission and death) more sustained compared to less severe \nillness\n▪VE during XBB predominance may wane more quickly against hospitalization compared to early variant \npredominant periods\n▪Vaccination during pregnancy provides protection against hospitalization for infants <6 months; protection may be \nhighest in the first 3 months\n▪CDC will continue ongoing monitoring of VE, including for all outcomes of interest and for all authorized COVID -19 \nvaccines in the U.S. with a focus on assessing new policy recommendations and VE in populations at higher risk of \nsevere COVID -19Conclusions: updates to VE of bivalent COVID -19 boosters\n60\nCDC COVID -19 Vaccine Effectiveness and \nPolicy Team\n▪Amadea Britton\n▪Allison Ciesla\n▪Monica Godfrey\n▪Eric Griggs\n▪Katherine Fleming -Dutra\n▪Dani Moulia\n▪Morgan Najdowski\n▪Erica OkwuaziVE platforms teams, including:\n▪Sarah Ball\n▪Angela Campbell\n▪Jennifer DeCuir\n▪Monica Dickerson\n▪Margaret Dunne\n▪Kiara Everett\n▪Shikha Garg\n▪Victoria Lazariu\n▪Patrick Mitchell\n▪Palak Patel\nAnd many more!!!Acknowledgements\n61▪Caitlin Ray\n▪Sarah Reese\n▪Elizabeth Rowley\n▪Regina Simeone\n▪Zach Smith\n▪Diya Surie\n▪Mark Tenforde\n▪Zack Weber\n▪Laura Zambrano▪Sara Oliver\n▪Josephine Mac\n▪Amanda Payne\n▪Lauren Roper\n▪Laura Steinhardt\n▪Evelyn Twentyman\n▪Megan Wallace\n▪Ryan Wiegand\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the \nofficial position of the Centers for Disease Control and Prevention.Questions?", "summary": "cdc.gov/coronavirus Epidemiology of COVID -19-Associated Hospitalizations,  including in Pregnant Persons and Infants Fiona Havers, MD, MHS, FIDSA Team Lead, RESP -NET Hospitalization Surveillance Team Commander, US Public Health Service Coronavirus and Other Respiratory Viruses Division National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention Advisory Committee on Immunization Practices June 23, 2023 COVID -19-associated hospitalizations COVID -NET:…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/02-COVID-Havers-Galang-Link-Gelles-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 62}
{"title": "03 COVID Jones 508", "content": "cdc.gov/coronavirusInfection -induced and hybrid immunity\nJefferson Jones, MD MPH FAAP\nCDR, US Public Health Service\n\nShifts in vaccine -induced, infection -induced, and hybrid immunity against SARS -CoV-2 \namong blood donors aged ≥16 years —United States, Quarter 2 2021 –Quarter 3 2022\nNo infection or vaccination\nVaccine only -induced \nantibodies\nInfection only -induced \nantibodies\nBoth infection and \nvaccination -induced \nantibodies (hybrid immunity)\nJones MMWR 2023: Data from a longitudinal, national cohort of \n>70,000 blood donors. Vaccine history is from self report. Infection \nhistory is based on presence of anti -nucleocapsid antibodies. \nShifts in vaccine -induced, infection -induced, and hybrid immunity against SARS -CoV-\n2 among people aged ≥16 years by age group —United States, Q2 2021 –Q3 2022\nNo infection or vaccination\nVaccination without previous \ninfection\nPrevious infection without \nvaccination\nBoth previous infection and \nvaccination (hybrid \nimmunity)\n16–29 years 30–49 years30–49 years\n50–64 years ≥65 years\nJones MMWR 2023: Data from a longitudinal, national \ncohort of >70,000 blood donors. Vaccine history is from \nself report. Infection history is based on presence of anti-\nnucleocapsid antibodies. \nQuantitative anti -spike antibody titers by age group \nand by infection and vaccine status, Jul -Oct 2022\nPrevious infection, \nunvaccinatedPrevious infection, \nvaccinatedVaccinated, no previous \ninfection\nSpike antibody titers (BAU/ml)\n16–29               30 –49            50 –64  ≥65\nAge (years)                \nSource: CDC (unpublished). Data from nationwide blood donor cohort\nVaccine history is from self report. Infection history is based on presence of anti -nucleocapsid antibodies. N=2,553 N=15,437 N=27,130 N=26,034 N=3,711 N=44,486 N=21,281\n63828993\n0102030405060708090100\nMar-Apr May-Jun Jul-Aug Sep-Oct Nov-DecSeroprevalence (%)\nMonth7585929799\n0102030405060708090100\nMar-Apr May-Jun Jul-Aug Sep-Oct Nov-DecSeroprevalence (%)\nMonthPediatric infection -induced and combined (vaccine -and infection -induced) \nSeroprevalence from U.S. commercial laboratories —March –December 2022\nSource: https://covid.cdc.gov/covid -data -tracker/#pediatric -seroprevalence and unpublished data (CDC) Data from repeat, cross -sectional study on blood specimens collected by \ncommercial laboratories. Vaccine history is unknown in this study. Infection -induced seroprevalence estimated from blood specime ns tested for anti -nucleocapsid antibodies: \nthe number of specimens per 2 -month collection period were, by age group: 6 –11 months: 157; 12 –23 months: 724; 2 –4 years: 2,165; 5–11 years: 9,247; and 12 –17 years: 14,570.  \nCombined (vaccine -and infection -induced seroprevalence estimated from specimens tested for both spike and nucleocapsid antibodi es: >99% of samples tested for anti -\nnucleocapsid antibodies were tested for anti -spike antibodies. 5Infection -induced Combined (vaccine -and infection -induced) \n\nAntibody titers depend more on history of infection and \nvaccination than age\n6–23 month    2 –4 yrs 5– 11 yrs 12–17 yrs\nAge group 10000\n1000\n100\n10Spike antibody titers (BAU/ml)N=612 N=1,769 N=13,785 N=8,299Spike antibody titers (BAU/ml)\nPrevious infection, \nunvaccinatedPrevious infection, \nvaccinatedVaccinated, no \nprevious infection\n*Does not include specimens with no detectable antibodies\nSource: CDC (unpublished)National blood donor seroprevalence study\nAges ≥16 years, Jul –Oct 2022National pediatric commercial lab seroprevalence study\nAges 6 months –17 years, Nov –Dec 2022, among \nspecimens with antibodies*N=3,711 N=44,486 N=21,281\nRBD Ab levels by history of infection and vaccination \nstatus— children 6 mo—17+ yrs, PROTECT study\n0.000.010.020.03RBD AUC6 months — 17+ years\n1 infection only n=175\n2 infections only n=201 dose only n=36\n1 dose + infection only n=22\nmRNA primary series only n=306\nmRNA primary series + ³1 infection only n=251\nBooster* only n=47\nBooster+ ³1 infection only n=125\nAntigen exposures\nBlood draw within 6 months of immune modifying event, time between immune modifying events is <365 days. \nRDB AUC:  area under the curve of receptor -binding domain antibodies, a quantitative measure of binding antibodies. \n*Booster Bivalent and monovalent boosters grouped together. \nLyski, Z and Porter, C. Unpublished data from the PROTECT cohort. PROTECT protocol: https://www.ncbi.nlm.nih.gov/pmc/articles /PM C9377426/\nRBD Ab levels by history of infection and vaccination status \nby age group —children 6 mo—17+ yrs, PROTECT study\nImmune -modifying events (in any order)\n0.000.010.020.03RBD AUC6 months — <5 years\n1 Infection only n=33\n2 infections only n=61 Dose+ infection only n=4\nmRNA primary series only n=13\nmRNA primary series + ³1 infection only n=17\nBooster+ infection n=1\nAntigen exposures1 dose only n=1\nBooster* only n=1\n0.000.010.020.03RBD AUC6 months — <5 years\n1 Infection only n=33\n2 infections only n=61 Dose+ infection only n=4\nmRNA primary series only n=13\nmRNA primary series + ³1 infection only n=17\nBooster+ infection n=1\nAntigen exposures1 dose only n=1\nBooster* only n=1\n0.000.010.020.0312-17+RBD AUC\nAntigen exposures1 infection only n=41\n2 infections only n=91 dose only n=12\n1 dose + infection only n=5\nmRNA primary series only n=125\nmRNA primary series + ³ 1infection only n=64\nBooster* only n=16\nBooster*+ ³ 1 infection only n=65\n0.000.010.020.0312-17+RBD AUC\nAntigen exposures1 infection only n=41\n2 infections only n=91 dose only n=12\n1 dose + infection only n=5\nmRNA primary series only n=125\nmRNA primary series + ³ 1infection only n=64\nBooster* only n=16\nBooster*+ ³ 1 infection only n=65\n0.000.010.020.03RBD AUC5-11\n1 infection only n=71\ndose 1 only n=23\n1 dose + infection only n=15\nmRNA primary series only n=169\nmRNA primary series + ³1 infection only n=172\nMonovalent booster only n=31\nBooster+ infection ³1 infection only n=61\nAntigen exposures2 infections only n=10\n0.000.010.020.03RBD AUC5-11\n1 infection only n=71\ndose 1 only n=23\n1 dose + infection only n=15\nmRNA primary series only n=169\nmRNA primary series + ³1 infection only n=172\nMonovalent booster only n=31\nBooster+ infection ³1 infection only n=61\nAntigen exposures2 infections only n=10n= 72 n= 552 n= 337\nSARS -CoV-2 neutralizing antibody ( nAb) studies\n▪In unvaccinated persons, infection -induced nAb titers highest against variants \nsimilar to the variant that infected the person1\n▪nAb titers in people with hybrid immunity may wane slower than in \npeople vaccinated without infection2\n–Infection after vaccination may be moderated by imprinting3\n▪Omicron\n–Omicron variants demonstrate greater escape from neutralization than older \nvariants1–2,4–6\n–Additional vaccine doses beyond primary series increase Omicron nAb titers4,5\n–Hybrid immunity results in higher Omicron nAb titers than immunity from \ninfection or vaccination alone, including to recent Omicron subvariants4\n1 Rössler 2022 NEJM ; 2 Qu 2022 NEJM ; 3 Wheatley Trends Immunol 2021 ; 4 Kurhade 2023 Nat Med ; \n5 Gaebler 2022 OFID ; 6 Barateau 2023 Sci Transl Med\nOther SARS -CoV-2 immunity laboratory study highlights\n▪Hybrid immunity appears to result in stronger more robust immune response \nusing other measures as well, including\n–\n–\n–Infection -induced and hybrid immunity result in higher IgA titers than \nvaccine -induced immunity1,2\nHybrid immunity may result in higher proportion of anti -spike memory \nB cells than vaccination alone3\nHybrid immunity induces T cells and antibodies directed against non -\nspike viral antigens4\n▪T-cell immunity from both infection and vaccination well preserved against \nOmicron4\n–Cellular immunity likely important in preventing severe disease5\n1 Barateau 2023 Sci Transl Med ; 2 Sheikh -Mohamed Immunol Rev 2022 ; \n3 Bednarski 2022 mBio ; 4 Naranbhai 2022 Cell ; 5 Moss 2022 Nature\nSystematic review of protection against Omicron from infection, hybrid with \nmonovalent primary series, and hybrid with first monovalent booster\nBobrovitz 2023 Lancet\nConclusions\n▪SARS -CoV-2 infection can cause severe disease, death, and long -term morbidity, whereas COVID -19 \nvaccination is safe and effective at preventing severe COVID -19 disease\n▪The proportion of people with immunity from infection or hybrid immunity has increased\n▪Immunity following vaccination and infection wanes over time, and both monovalent primary series \nvaccination and history of pre -Omicron infection provided much lower protection during Omicron than \nduring prior COVID -19 waves\n▪Compared with protection from infection or vaccination alone, hybrid immunity likely better protects \nagainst infection and severe disease with Omicron\n▪Stronger protection is likely provided when the infecting variant is similar to the circulating variant, but this \nmay be complicated by imprinting\n▪Current protection likely influenced by both cumulative number of vaccine doses, number of times \ninfected, and timing of most recent vaccination or infection, and how closely the circulating variant \nmatches the vaccine or prior infection\n▪Conclusions apply to both children and adults\nAcknowledgments\n▪Tarayn Fairlie\n▪Melissa Briggs -Hagen\n▪Melissa Coughlin\n▪Natalie Thornburg\n▪Claire Midgley▪Ian Plumb\n▪Amadea Britton\n▪Ruth Link -Gelles\n▪Amanda Payne\n▪PROTECT team\nFor more information, contact CDC\n1-800-CDC-INFO (232-4636)\nTTY:  1- 888- 232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the \nofficial position of the Centers for Disease Control and Prevention.", "summary": "cdc.gov/coronavirusInfection -induced and hybrid immunity Jefferson Jones, MD MPH FAAP CDR, US Public Health Service  Shifts in vaccine -induced, infection -induced, and hybrid immunity against SARS -CoV-2  among blood donors aged ≥16 years —United States, Quarter 2 2021 –Quarter 3 2022 No infection or vaccination Vaccine only -induced  antibodies Infection only -induced  antibodies Both infection and  vaccination -induced  antibodies (hybrid immunity) Jones MMWR 2023: Data from a…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/03-COVID-Jones-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 14}
{"title": "03 Meningococcal Ortega Sanchez 508", "content": "Economics of Potential Pentavalent Meningococcal \nConjugate Vaccine (MenABCWY) versus the Current \nMenACWY and MenB vaccines for US Adolescents \nA SUMMARY REPORT COMPARING MODELS FROM: \nPfizer AND CDC \nIsmael R. Ortega-Sanchez, PhD \nNCIRD/CDC \nMeningococcal ACIP Meeting, October 25, 2023 \nDisclaimer : The findings and conclusions in this report are t hose of the authors and do not necessarily represen t the views of \nthe Centers for Disease Control and Prevention. \nNational Center for Immunization & Respiratory Dise ases \n1\nConflict of interest Conflict of interest Conflict of interest Conflict of interest \n•Pfizer model : Shannon Sullivan et al., [complete authors list a nd \naffiliations, upon request ] \n•Pfizer manufactures pentavalent (MenABCWY) vaccine \n•Evidera Inc. (France, USA, Hungary) was funded by Pfizer \n•CDC model : Ismael R Ortega-Sanchez et al. from CDC [complete \nauthors list and affiliations, upon request ] \n•All authors: No conflicts of interest \n2\n3 Policy questions for economic modeling 3 Policy questions for economic modeling 3 Policy questions for economic modeling 3 Policy questions for economic modeling •Should the pentavalent vaccine (MenABCWY) be consid ered as an \noption for MenACWY/MenB vaccination in people curren tly \nrecommended to receive both vaccines?  (PICO 1) \n•Should the pentavalent vaccine (MenABCWY) be include d as an \noption for people currently recommended to receive MenACWY only? \n(PICO 2) \n•Should the pentavalent vaccine (MenABCWY) be includ ed as an \noption for people currently recommended to receive MenB only? \n(PICO 3) \n3\nEconomic analysis Economic analysis Economic analysis Economic analysis Question : Is vaccinating adolescents 11-16 years old with P entavalent (MenABCWY) \nvaccine series to prevent Invasive Meningococcal Di sease in adolescents cost-effective ?\nComparator Interventions \nBase-case scenario: What is the incremental cost-effectiveness of vaccinating healthy \nadolescents 11-12 and 16 years old with Pentavalent  vaccine relative to using MenACWY \nand MenB vaccines ? MenACWY vaccine: one dose at 11-12 years and one dose at 16 years. (\nQ-Q)\nMenB vaccines: two doses at 16 years. (\nB-B)Use of Pentavalent \nMenABCWY vaccine \ncombined either as \nQ-P-B\nP-P-N\nor  Q-P-P\n4\nDescription of Current and Hypothetical Description of Current and Hypothetical Description of Current and Hypothetical Description of Current and Hypothetical \nVaccines and Vaccination Strategies Vaccines and Vaccination Strategies Vaccines and Vaccination Strategies Vaccines and Vaccination Strategies \nStandard of Care (SoC) Potential vaccination strategies \nFirst dose Second dose Key Label First dose Second dose Third dose Key Label \nAt 11-12 yrs \nold with \nMenACWY At 16 yrs old \nwith MenACWY Q-QAt 11-12 yrs old \nwith MenACWY At 16 yrs old with \nMenABCWY At 16.5 yrs old with \nMenB Q-P-B\nAt 11-12 yrs old \nwith MenABCWY At 16 yrs old with \nMenABCWY None (N) P-P-N\nAt 16 yrs old \nwith MenB At 16.5 yrs old \nwith MenB B-BAt 11-12 yrs old \nwith MenACWY At 16 yrs old with \nMenABCWY At 16.5 yrs old with \nMenABCWY Q-P-P\nSoC= Standard of care (current vaccination programs: Q-Qand B-B)\nMenABCWY = Potential pentavalent vaccine ( P) with serogroups A, B, C W Y \nMenACWY = currently recommended quadrivalent vaccine ( Q) for serogroups A, C, W, Y, \nMenB =currently recommended monovalent vaccine for serogro up B5\nPfizer Pfizer Pfizer Pfizer and and and and CDC CDC CDC CDC : incremental cost : incremental cost : incremental cost : incremental cost- - --effectiveness effectiveness effectiveness effectiveness \nanalyses of vaccination strategies with pentavalentanalyses of vaccination strategies with pentavalentanalyses of vaccination strategies with pentavalentanalyses of vaccination strategies with pentavalent\nPolicy \nquestion Incremental \nanalysis Pfizer CDC Vaccine Price \nused for \nPentavalent ** \nPICO #1 Q- P-B vs SoC Included* Included $250 (private) / \n$187.5 (public) \nPICO #2 P-P-N vs Q-Q Included Included $210 (private) / \n$157.5 (public) \nPICO #3 Q- P-Pvs SoC Included Included $210 (private) / \n$157.5 (public) \nSoC = Standard of care (current vaccination programs: Q-Q and B-B) \n* Included in Pfizer technical report updates until August 2023, not inc luded in the Pfizer technical report update of October 2023 \n** The price of $250 (private) / $187.5 (public) is for strategies using a single dose of pentavalent and the price of   $210 (private) / $157.5 \n(public) for strategies using ≥2 doses of pentavale nt 6\nFocus on key features for model comparison Focus on key features for model comparison Focus on key features for model comparison Focus on key features for model comparison •Modeling approach \n•Targeted population(s) \n•Perspective (healthcare vs. societal) \n•Intervention strategies and comparators \n•Inputs for IMD burden, vaccine efficacy, and costs \n•Incidence of IMD rates and sequelae outcomes \n•Direct and indirect costs of IMD \n•Intervention: efficacy, duration of protection, saf ety and program costs \n•Assumptions \n•Strong, influential assumptions \n7\nModeling design and assumptions Modeling design and assumptions Modeling design and assumptions Modeling design and assumptions \nPfizer CDC \nStatic analytical decision-making models ✔ ✔\nSensitivity analyses (and probabilistic simulation) ✔(✔)✔(✔)\nHypothetical population: US cohort of adolescents ≥ 11 years of age ✔ ✔\nTime Frame: 15 years (from 11-25 years) ✔ ✔\nAnalytic Horizon: Temporary disability (acute witho ut sequelae) and \nLife Expectancy (permanent sequalae or premature mo rtality) ✔\n✔✔\n✔\nDiscount rate: 3% ✔ ✔\nYear of health and economic outcomes measured: 2022 ✔ ✔\nSocietal perspective (and healthcare perspective) ✔(✔)✔(✔)\n8\nInputs and main outcomes Inputs and main outcomes Inputs and main outcomes Inputs and main outcomes \nPrevention of: •IMD cases \n•IMD-associated sequelae \n•IMD-associated deaths \nQALYs saved $/QALY saved Number needed to vaccinate (NNV) to avert an: •IMD case \n•IMD death Pfizer CDC \n/uni2714 /uni2714/uni2714 /uni2714/uni2714 /uni2714 /uni2714 /uni2714/uni2714 /uni2714\n/uni2714/uni2714\nIMD = invasive meningococcal disease HCRU = healthcare resource utilization QALY= quality-adjusted life year \n9\nPfizer Pfizer Pfizer Pfizer and and and and CDC CDC CDC CDC models comparison: models comparison: models comparison: models comparison: \nSelected inputs Selected inputs Selected inputs Selected inputs \n•Cost of vaccine and vaccine administration \n•IMD incidence for pre vaccine and vaccine era \n•Initial vaccine effectiveness and waning over time \n•IMD associated permanent sequalae \n•Age and serogroup specific Case Fatality Rate (CFR)\n•Acute IMD: QALY scores and unitary direct costs \nIMD = Invasive meningococcal disease QALY= Quality-adjusted life years \nNote : Starting this slide and forward, to specifically identify changes and updates from those presented l ast June 2023, the \ntext will appear either highlighted, or with the wor d updated at the top of the slide or table. 10 \nPfizer Pfizer Pfizer Pfizer vaccine price for a dose of Pentavalent \n11 Vaccination \nStrategies March to June \n2023* August 2023** October 2023*** \nWith one dose \nPrivate $240 \n($230-$250) $250.0 $250.0 \nPublic -- 187.5 187.5 \nWith ≥ 2 doses \nPrivate $240 \n($230-$250) $250.0 $210.0 \nPublic -- 187.5 $157.5 \n* From March to June 2023, Pfizer submitted various technical reports using the pentavalent vaccine prices of $240 (range $230 to $250) per dose \n** In August 2023, Pfizer submitted a new technical report updating the penta valent prices to $250 (private) / $187.5 (public) per dose \n*** In October 2023, Pfizer submitted a newer technical report updating the pen tavalent prices to $210 (private) / $157.5 (public) per dose for strat egies using ≥2 doses \nof pentavalent \nPfizer Pfizer Pfizer Pfizer and and and and CDC CDC CDC CDC : Vaccine cost per vaccine type, : Vaccine cost per vaccine type, : Vaccine cost per vaccine type, : Vaccine cost per vaccine type, \nand vaccine administration costs and vaccine administration costs and vaccine administration costs and vaccine administration costs \n* 2023 public and private sector cost per dose; VFC  Current CDC Vaccine Price List, CDC. \n**2023 Proportions of vaccine purchased at private sector and procurement from either private or priva te providers were based on different sources (i.e., \nhttps://www.cdc.gov/nchs/data/nhis/earlyrelease/ins ur202305_1.pdf , Glazner et al., Pediatrics 2009) \n*** Calculated using a hypothetical range of prices  for public and private as reported by Pfizer Inc. for MenABCWY .\n¶  Assumption considers wastage from either open vi al, mishandling or outdated shelf life. \nNote: CDC model : rates and associated costs of hypothetical vaccin e associated adverse events, non shown here, were a pplied to all vaccines. \nTrotter et al., BMJ 2002 https://pubmed.ncbi.nlm.nih.gov/11934772/ ; Ortega-Sanchez et al., CID 2008. https://pubmed.ncbi.nlm.nih.gov/18171206/ Quadrivalent (Q)* Men B (B)* Pentavalent (P) \nQ-P-B\n(single dose) P-P-N & Q- P-P\n(≥2 doses) \npublic sector cost for vaccine $105.6 $141.84 $187.5 $157.5 \npublic sector admin cost $15.0 $15.0 $15.0 $15.0 \nprivate sector cost for vaccine $156.0 $211.32 $250.0 $210.0 \nprivate sector admin cost $30.0 $30.0 $30.0 $30.0 \n% vaccine purchased at public sector price ** 53.75% 53.75% 53.75% 53.75% \n% vaccinations obtained from private sector provide rs ** 78% 78% 78% 78% \nPfizer : weighted cost per dose + administration $155.61 $ 200.67 $243.11*** $208.48*** \n% vaccine waste¶ 4.5% 4.5% 4.5% 4.5% \nCDC : weighted cost per dose + administration $162.61 \n($128 - $191) $ 209.70 \n($155 - $250) $254.05*** \n($205 - $290) $217.86*** \n($192 - $250) \n12 \nPfizer Pfizer Pfizer Pfizer and and and and CDC CDC CDC CDC : Average Annual Incidence in Vaccine : Average Annual Incidence in Vaccine : Average Annual Incidence in Vaccine : Average Annual Incidence in Vaccine \nSerogroups BCYW by Age per 100,000 used in the mode ls Serogroups BCYW by Age per 100,000 used in the mode ls Serogroups BCYW by Age per 100,000 used in the mode ls Serogroups BCYW by Age per 100,000 used in the mode ls \nSource: CDC Model : Age-by-year-specific data from ABC Core Surveilla nce and NNDSS for PreVaxs and Vax eras \nPfizer model : Pre Vax Era : Mbaeyi et al. Incidence of Meningococcal Disease B efore and After Implementation of Quadrivalent Meni ngococcal Conjugate Vaccine in \nthe United States.  JAMA Pediatr. 2020;174(9):843-8 51. doi:10.1001/jamapediatrics.2020 \nVax Era : US CDC Enhanced Meningococcal Disease Surveillanc e Report, 2017. Enhanced Meningococcal Disease Surveillance Report,  2017 (cdc.gov) \nNote: Trend and variability across years were used for range of uncertainties and sensitivity analyses  •Rates of IMD disease remain relatively higher in late adolescence, but in general rates have been declining for all age groups. \n•Overall, IMD incidence rates are \none fifth to \none sixth of those \nfrom recent pre-vaccine era \n13 \nPfizer Pfizer Pfizer Pfizer and and and and CDC CDC CDC CDC : : : : Initial vaccine effectiveness Initial vaccine effectiveness Initial vaccine effectiveness Initial vaccine effectiveness by by by by \nvaccine and serogroup vaccine and serogroup vaccine and serogroup vaccine and serogroup \nQUADRIVALENT MEN B PENTAVALENT \nBase-case Low High Base-case Low High Base-case Low High \nFirst DOSE MenACWY 93% 73% 98% 93% 73% 98% \n2nd + DOSE MenACWY 97% 73% 98% 97% 73% 98% \nFirst DOSE MenB* 60% 18% 74% 60% 18% 74% \n2nd + DOSE MenB 85% 50% 99% 85% 50% 99% \nValues and assumptions on initial protection are ba sed on various sources: \nPhase 3 noninferiority initial vaccine efficacy by single dose (at 11-12yrs) and second-dose (16yrs) o f pentavalent (Men ABCWY) vaccine as reported by Pf izer (data on file). \nUpdated Pfizer Technical reports on Cost-effectivene ss of the Pentavalent Meningococcal Vaccine (MenABC WY) in the US \nCohn AC, MacNeil JR, Harrison LH, et al. Active Bac terial Core Surveillance (ABCs) Team and MeningNet S urveillance Partners. Effectiveness and Duration of  Protection of \nOne Dose of a Meningococcal Conjugate Vaccine. Pedi atrics. 2017 Feb;139(2):e20162193. doi: 10.1542/ped s.2016-2193. PMID: 28100689; PMCID: PMC8353579. \n*The range for VE efficacy for first dose of MenB i s from Castilla et al. NEJM 2023 https://www.nejm.org/doi/full/10.1056/nejmoa2206433\n14 \nPfizer CDC Pfizer Pfizer Pfizer Pfizer and and and and CDC CDC CDC CDC : : : : Assumption about residual Assumption about residual Assumption about residual Assumption about residual \nprotection by vaccine and serogroup protection by vaccine and serogroup protection by vaccine and serogroup protection by vaccine and serogroup \nAssumptions on residual protection are based on var ious sources: \n•Sero-protection is assumed to persist 4-5 years for  a single dose of MenACWY and MenABCWY (based on hSBA sero bactericidal assay from Pfizer’s clinical trial s report) \n•Pfizer Technical report on Cost-effectiveness of th e Pentavalent Meningococcal Vaccine (MenABCWY) in t he US. \n•The pink-shaded areas denote a higher level of unce rtainty of the waning assumption beyond available s urveillance or Phase 3 data\nCYW \nBB\nCYW CYW B\n15 \nPfizer CDC Pfizer Pfizer Pfizer Pfizer and and and and CDC CDC CDC CDC : : : : Long Long Long Long- - --term sequalae and CFR term sequalae and CFR term sequalae and CFR term sequalae and CFR \nincluded in the models included in the models included in the models included in the models \n*  Range is a +/- 20% of base-case ** In addition to CFR, it is assumed an increased r isk of excess mortality of \n1.21 (1.06-1.37); i.e., reduced life expectancy amo ng survivors with sequalae Long-term sequelae Probability (range for SA) \nSkin scarring 7.6       \n(0 - 19) \nSingle amputation 1.9     \n(0.5 - 10) \nMultiple amputations 1.2     \n(0.02 - 6) \nHearing loss 8.8        \n(2 - 20) \nSignificant long term neurologic disability 2.1   \n(0.02 - 11) \n28.5% (24.2 - 34.3)* 21.6% \nCase Fatality Rate (CFR) For serogroups BCWY Case Fat ality Rate (CFR) For serogroups BCWY \nCFR in 11-25 years ** 12.5% (10 to <15yrs) \n8% (15 to <25yrs) CFR in 11-25 years*** 12.3% \n(8.9 – 15.5) \n*** Weighted average by age and serogroup proportio ns (Lower value in \nrange is from serogroup B, high value is from serog roups CWY).   \nSA=Sensitivity analysis 16 \nPfizer Pfizer Pfizer Pfizer and and and and CDC CDC CDC CDC : Direct costs and QALY scores : Direct costs and QALY scores : Direct costs and QALY scores : Direct costs and QALY scores \nused in modeling acute phase of IMD used in modeling acute phase of IMD used in modeling acute phase of IMD used in modeling acute phase of IMD \nCDC Pfizer \nDirect cost: Medical unitary costs Public health response Medical cost for an IMD acute phase \nonly  $48,983 a\nPublic response per isolated case \n$13,547 Medical cost of IMD acute phase by type d\nMeningitis $81,782 \nSepticemia $115,899 \nUnspecified $101, 320 \nIMD cases without permanent  sequelae during acute phase Disutility: 0.12 for a year b\nEquivalent QALDs:  46.24 days Disutility: 0.4 to 0.51 for a year e\nEquivalent QALDs: 146 to 186 days \nIMD cases without permanent sequelae after acute phase Disutility: 0.083 for a year c\nEquivalent QALDs:  14.8 days Disutility: 0.03 (range +/- 20%) f\nDuration: 9 years \nEquivalent QALDs: 100 days \na. Medical costs were adjusted to 2022 using the GDP  implicit deflator index.  Public response costs we re based per hour wage of public health worker, hour s of work \nper case, cost of chemoprophylaxis, average number of contacts per case. \nb. QALD = quality-adjusted life days lost c. Assumption after acute phase based on 2/3 of disu tility during acute phase for patients without perm anent sequelae \nd. Unitary cost per type of IMD based on  Davis et a l \nhttps://pubmed.ncbi.nlm.nih.gov/21278486/ \ne. Derived from Lecocq et al. Vaccine 2016 https://pubmed.ncbi.nlm.nih.gov/27002504/ \nf. Koomen et al.  Qual Life Res. 2005  https://pubmed.ncbi.nlm.nih.gov/16110936/ and Schmand et al  J Infect. 2010 https://pubmed.ncbi.nlm.nih.gov/20659499/ \n17 \n*Updated from Monte Carlo Simulation using a sample  of 1000 iterations.  Preliminary estimates.                                            ICER = Increme ntal cost-effectiveness ratio \n** Both total net costs estimates relied on $250 (p rivate)/$187.5 (public) cost per dose of pentavalen t vaccine \n-10.54 -1.21 \n5.0% 5.0% 90.0% \n0.0 0.2 0.4 0.6 0.8 1.0 \n-20 -15 -10 \n-5 \n05\n10 \nValues in Millions ($) CDC : Cumulative probability of ICER per QALY saved: Q- P-B vs SoC Policy question 1: Policy question 1: Policy question 1: Policy question 1: Pfizer Pfizer Pfizer Pfizer and and and and CDC*: CDC*: CDC*: CDC*: Pentavalent Pentavalent Pentavalent Pentavalent \nvaccine price vaccine price vaccine price vaccine price $250 $250 $250 $250 (private)/ (private)/ (private)/ (private)/$187.5 $187.5 $187.5 $187.5 (public)** (public)** (public)** (public)** \nPfizer \nQ-P-B vs SoC CDC \nQ-P-B vs SoC \nIMD cases saved 0 <0 – 5\nIMD deaths saved 0 0 – 3\nLY saved 0 <0 – 28 \nQALYs saved 0 <0 – 42 \nTotal Net Costs (millions) ($426)** ($564)** \n$/QALY saved Cost savings \n($/QALY <0) Cost savings \n($/QALY <0) What is the incremental effectiveness and cost-effec tiveness of vaccinating healthy adolescents 11-12 and 16 \nyears old with Pentavalent vaccine relative to using MenACWY and MenB vaccines ? \nBaseline: -$3,050,277 \n18 \nPolicy question 2: Policy question 2: Policy question 2: Policy question 2: Pfizer:  Pfizer:  Pfizer:  Pfizer:  Pentavalent Pentavalent Pentavalent Pentavalent vaccine price vaccine price vaccine price vaccine price \n$$ $$210 (private)/$157.5 (public)* 210 (private)/$157.5 (public)* 210 (private)/$157.5 (public)* 210 (private)/$157.5 (public)* \nP-P-N vs Q-Q\nIMD cases saved 41 IMD deaths saved 4 LY saved 86 QALYs saved 164 Total Net Costs (millions) \n$319 \n$/QALY saved $1.94 Million What is the incremental effectiveness and cost-effec tiveness of vaccinating healthy adolescents 11-12 and 16 \nyears old with Pentavalent vaccine relative to using MenACWY only? \nICER = incremental cost-effectiveness ratio LTS = Long-term sequelae \n* Updated Pfizer estimates with  pentavalent vaccin e price $210 (private)/ $157.5 (Public) and \ntornado figure 19 \n1.73 9.15 \n5.0% 4.8% 90.2% \n0.0 0.2 0.4 0.6 0.8 1.0 \n0369\n12 15 \nValues in Millions ($) CDC : Cumulative probability of ICER per QALY saved: P- P-N vs Q-QPolicy question 2: Policy question 2: Policy question 2: Policy question 2: CDC*: CDC*: CDC*: CDC*: Pentavalent vaccine price Pentavalent vaccine price Pentavalent vaccine price Pentavalent vaccine price \n$210 (private)/$157.5 (public) $210 (private)/$157.5 (public) $210 (private)/$157.5 (public) $210 (private)/$157.5 (public) ** ** ** ** \nP-P-N vs Q-Q\nIMD cases saved 12 \nIMD deaths saved 1\nLY saved 27 \nQALYs saved 58 \nTotal Net Costs (millions) $270 \n$/QALY saved $4.7 Million What is the incremental effectiveness and cost-effec tiveness of vaccinating healthy adolescents 11-12 and 16 \nyears old with Pentavalent vaccine relative to using MenACWY only? \nBaseline: $4,693,778 \n*Updated from Monte Carlo Simulation using a sample of 1000 iterations.  Preliminary estimates \n** Updated Pfizer estimates with  pentavalent vacci ne price $210 (private)/ $157.5 (Public) ICER = Inc remental cost-effectiveness ratio  20 \nPolicy question 3: Policy question 3: Policy question 3: Policy question 3: Pfizer Pfizer Pfizer Pfizer and and and and CDC: CDC: CDC: CDC: Pentavalent Pentavalent Pentavalent Pentavalent \nvaccine price $210 (private)/$157.5 (public)* vaccine price $210 (private)/$157.5 (public)* vaccine price $210 (private)/$157.5 (public)* vaccine price $210 (private)/$157.5 (public)* \nWhat is the incremental effectiveness and cost-effec tiveness of vaccinating healthy adolescents ≥16 years old \nwith Pentavalent vaccine relative to using MenB vaccine only ? \nPfizer \nQ-P-P vs SoC CDC** \nQ-P-P vs SoC \nIMD cases saved 4\n5\nIMD deaths saved 0\n0 - 2\nLY saved 9 26 \nQALYs saved 17 39 \nTotal Net Costs (millions) ($528) ($639) \n$/QALY saved Cost savings \n($/QALY <0) Cost savings \n($/QALY <0) \n* Updated Pfizer estimates using $210 (private)/$15 7.5 (public) cost per dose of pentavalent vaccine \n** Updated from Monte Carlo Simulation using a samp le of 1000 iterations.  Preliminary estimates                         ICER = Incremental cost-effectiv eness ratio \n-15.95 -0.58 \n5.0% 5.0% 90.0% \n0.0 0.2 0.4 0.6 0.8 1.0 \n-20 -15 -10 \n-5 \n05\n10 \nValues in Millions ($) CDC : Cumulative probability of ICER per QALY saved: Q- P-P vs SoC \nBaseline: -$3,063,131 \n21 \nLimitations Limitations Limitations Limitations \n•Factors not considered in Pfizer and CDC models that may result in overestimating the ICER \n(underestimating the cost-effectiveness) of MenABCW Y \n•In base-case: both models assumed \n•No protection against non-IMD \n•No indirect protection against IMD of unvaccinated individuals \n•Productivity losses incurred by caregivers for long -term specific sequelae are based on \nassumptions and partially included \n•Differences in key inputs among Pfizer and CDC models and the uncertainty in inputs data may expla in \nsome differences in results: \n•Duration of vaccine protection \n•Medical costs \n•Variability in IMD incidence and CFR data \n•Inclusion of different sequalae \n•QALY score for IMD cases without permanent sequelae\n•Pentavalent price for Q-P-B is uncertain: price used  here is the minimum expected. Higher prices will \nincrease total net cost & ICERs 22 \nConclusion Conclusion Conclusion Conclusion \n•In both Pfizer and CDC models , MenABCWY vaccine would reduce the IMD burden in adol escents \n•In both models, strategies with one or more doses o f the MenABCWY vaccine would save more or equal \nnumber of IMD cases. \n•PICO #1 : Q-P-B could be incrementally cost-saving (ICER QALY saved <0) rela tive to SoC \n•Q-P-B includes one dose of MenABCWY in substitution o f the second dose of MenACWY and first dose \nof MenB \n•PICO #2: P-P-N is incrementally costly (not cost saving) relative to Q-Q. \n•P-P-N included two doses of MenABCWY in substitution of the two doses of MenACWY ,\n•PICO #3: Q-P-P is likely cost saving (ICER QALY saved <0) relative to SoC \n•About 96% percent of iterations in the CDC model simulations have an ICER<0 \n•Q-P-P included two doses of MenABCWY in substitution  of the second dose of MenACWY and the first \nand second dose of MenB \n•Reasonable pentavalent price and duration of protec tion combined with careful design of \nvaccination interventions with MenABCWY would determ ine the cost or cost-saving value of the \npentavalent vaccine among adolescents ≥11 year of ag e \n23 \nAcknowledgements Acknowledgements Acknowledgements Acknowledgements \nFrom NCIRD/CDC •Lucy Alexandra McNamara \n•Jennifer Collins \n•Andrew Leidner \nAlso: •ACIP Meningococcal working group members \n24 \nEnd of Summary", "summary": "Economics of Potential Pentavalent Meningococcal  Conjugate Vaccine (MenABCWY) versus the Current  MenACWY and MenB vaccines for US Adolescents  A SUMMARY REPORT COMPARING MODELS FROM:  Pfizer AND CDC  Ismael R. Ortega-Sanchez, PhD  NCIRD/CDC  Meningococcal ACIP Meeting, October 25, 2023  Disclaimer : The findings and conclusions in this report are t hose of the authors and do not necessarily represen t the views of  the Centers for Disease Control and Prevention.  National Center for…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-25-26-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-10-25-26/03-Meningococcal-Ortega-Sanchez-508.pdf", "doc_date": "2023-10-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 25}
{"title": "04 Meningococcal Collins 508", "content": "Summary of EtRand proposed \nrecommendations for Pfizer’s MenABCWY\nvaccine \nJennifer Collins MD, MSc\nInterim Co -Lead, ACIP Meningococcal Vaccines Work Group\nOctober 25, 2023National Center for Immunization & Respiratory Diseases\nACIP Recommendations for Meningococcal Vaccines\n▪ Routine schedule \n–MenACWY : dose 1 at age 11 –12 years, booster dose at age 16 years\n–MenB (shared clinical decision -making): two doses at age 16–23 years (preferred age 16 –18 years)\n▪ Special situations\nIndicationMenACWY\n(age ≥2 months)MenB\n(age ≥10 years)\nMedical conditionsAsplenia X X\nComplement Deficiency X X\nComplement inhibitor use X X\nHIV infection X\nOtherSome microbiologists X X\nExposure during an outbreak X X\nTravel to hyperendemic areas X\nFirst -year college students X\nMilitary recruits X2\nMeningococcal vaccines licensed and \navailable in the United States\n▪MenACWY vaccines are interchangeable\n▪MenB vaccines are NOT interchangeableVaccine Trade Name Manufacturer Minimum age\nMenACWY -CRM Menveo GSK 2 months\nMenACWY -TT MenQuadfi Sanofi Pasteur 2 years\n3Vaccine Trade Name Manufacturer Minimum age\nMenB -4C Bexsero GSK 10 years\nMenB -FHbp Trumenba Pfizer 10 years\nPfizer’s MenABCWY Vaccine\n▪Licensed as a 2 -dose series (6-month interval) for individuals aged 10 –25 years\n▪Comprised of Trumenba (serogroup B) and Nimenrix (serogroups ACWY)\n–Trumenba\n•Consists of two purified recombinant lipidated FHbp antigens, one from \neach FHbp subfamily (A and B)\n•Currently licensed and available in U.S. (10 –25 years)\n–Nimenrix\n•Meningococcal group A, C, W, and Y polysaccharide tetanus toxoid \nconjugate vaccine\n•Not licensed in U.S. but used extensively in Europe and elsewhere for more \nthan a decade\n4\nPolicy Questions for 3 PICOs \n▪Should the pentavalent vaccine be included as an option for \nMenACWY/MenB vaccination in people currently recommended to \nreceive both vaccines ? \n▪Should the pentavalent vaccine be included as an option for people \ncurrently recommended to receive MenACWY only ? \n▪Should the pentavalent vaccine be included as an option for people \ncurrently recommended to receive MenB only ? PICO 1\nPICO 2\nPICO 3\n5\nGRADE Table 1: Combined Policy Question and PICO\nPolicy QuestionShould the pentavalent vaccine be included as an option for people currently recommended to \nreceive MenACWY and MenB, MenACWY only, or MenB only ?\nPopulationAll individuals aged 10 years or older currently recommended to receive MenACWY+MenB, \nMenACWY , or MenB vaccine\nIntervention Vaccination with Pfizer’s pentavalent ( MenABCWY ) vaccine\nComparison Vaccination with currently licensed MenACWY+MenB, MenACWY , or MenB vaccine\nOutcomes•Meningococcal disease caused by serogroups A, B, C, W, and Y ( as appropriate by PICO )\n•Short -term immunity\n•Persistent immunity\n•Interference with other recommended vaccines administered concurrently\n•Serious adverse events\n•Non -serious adverse events\n6\nHow PICOs Translate into Schedule Options for Healthy \nAdolescents –assuming MenB #1 at age 16 years\nLegend\nQ = MenACWY (quadrivalent)\nB = MenB\nP = MenABCWY (pentavalent)Options11–12 year \nolddose16 year old\ndose #116 year old\ndose #2\nStandard of care (MenACWY only) Q Q –\nStandard of care (MenACWY + MenB) Q Q+B B\nPICO 1 (MenABCWY as option for MenACWY + MenB) Q P B\nPICO 2 (MenABCWY as option for MenACWY) P P ±B\nPICO 3 (MenABCWY as option for MenB) Q P P\nCombination of all 3 PICOs P P P\n7\nSchedule options presented in June\nLegend\nQ = MenACWY (quadrivalent)\nB = MenB\nP = MenABCWY (pentavalent)Options11–12 year \nolddose16 year old\ndose #116 year old\ndose #2WG \nProposal\nStandard of care (MenACWY only) Q Q – N/A\nStandard of care (MenACWY + MenB) Q Q+B B N/A\nPICO 1 (MenABCWY as option for MenACWY + MenB) Q P B\nPICO 2 (MenABCWY as option for MenACWY) P P B\nPICO 3 (MenABCWY as option for MenB) Q P P\nCombination of all 3 PICOs P P P\n8\nSince June, the WG has refined the EtRand further \nconsidered possible implications of each PICO \n(especially PICO 3) based on\n▪ACIP members’ concerns raised during the June meeting\n–Cost effectiveness \n–Concerns about increasing exposure to B component related to reactogenicity, low \nburden of disease, and limitations to protection\n–Optimal timing of B component is often not age16 years\n–Fidelity to clinical trial data and licensure\n–Stocking and administration considerations\n▪Cost effectiveness analysis\n–Updates to quoted price of the pentavalent vaccine\n–Refinements to the CDC model\n9\nSummary of updated EtR\nPUBLIC HEALTH PROBLEM\nIs meningococcal disease a problem of public health importance? \n▪Incidence of meningococcal \ndisease is low and decreasing\n▪Causes very severe disease\n▪Poor outcomes even with \ntreatment\n–Case fatality 10 –15% \n–10–20% of survivors have \npermanent sequelae\n11WG interpretationPICO 1 \nMenABCWY vs. MenACWY + MenBPICO 2 \nMenABCWY vs. MenACWYPICO 3 \nMenABCWY vs. Men B\nYes Yes Yes\n\nBENEFITS & HARMS\n▪ Three randomized control trials studied\n–MenABCWY 2 doses (0, 6 months and 0, 12 months) vs. MenACWY -CRM 1 dose + MenB -FHbp 2 doses \n(0, 6 months)\n–Among ACWY -naïve and ACWY -primed participants\n–Available data facilitated assessment of select outcomes through GRADE\n•Short -term immunity\n•Persistent immunity\n•Serious adverse events\n•Non -serious adverse events\n▪ Othe r important benefits and harms were not assessed through GRADE but factored into WG \ninterpretations\n–Increased r eactogenicity of MenB relative to MenACWY\n–Limitations to B protection\n•Low VE expected following a single dose\n•Rapidly waning protection following 2 -dose series\n•Multiple studies demonstrating MenB vaccination has no effect on meningococcal carriage \n12\nBENEFITS AND HARMS: Summary of GRADE\nType Outcome ImportanceDesign \n(# studies)FindingsEvidence type*\nHealthy Increased risk\nBenefitsMeningococcal disease \ncaused by serogroups, A, B, \nC, W, and YCritical n/a No data available ND ND\nShort -term immunity Critical RCT (1)Serogroup -specific seroresponses one month after \nthe first trial dose of ACWY -or B-containing vaccine \noccurred as often or more often in the pentavalent \ngroup compared with the control groupModerate Low\nPersistent immunity Important RCT (2)Seroresponse rates by serogroup were similar:\n-48 months after 2 doses pentavalent vs. 54 \nmonths after 1 dose MenACWY -CRM\n-48 months after 2 doses pentavalent vs. 2 doses \nMenB -FHbpLow─\nmoderateLow\nHarmsSerious adverse events Critical RCT (3)Significantly more SAEs occurred in the pentavalent \ngroup vs. comparison group; none were attributed \nto the vaccineLow Very low\nNon -serious adverse \neventsImportant RCT (3)Significantly more non -serious adverse events \noccurred in the pentavalent group vs. comparison \ngroupLow Very low\nInterference with other \nrecommended vaccines \nadministered concurrentlyImportant n/a No data available ND ND\n13 *Downgrades primarily related to indirectness of intervention and comparison groups relative to PICOs, people at increased ri sk not being included, and wide confidence intervals for adverse events\nBENEFITS & HARMS –Work Group interpretations\n14QuestionPICO 1 \nMenABCWY vs. MenACWY + \nMenBPICO 2 \nMenABCWY vs. \nMenACWYPICO 3 \nMenABCWY vs. Men B\nHow substantial are the \ndesirable anticipated \neffects?SmallMinimal, small, or \nmoderateMinimal\nHow substantial are the \nundesirable anticipated \neffectsSmall Minimal or small Minimal or small\nDo the desirable effects \noutweigh the \nundesirable effects?Favors interventionFavors intervention, \ncomparison, or bothFavors intervention or \ncomparison\nWhat is the overall \ncertainty?Varies by group Varies by group Varies by group\n15VALUES\n▪Limited data were available \n–Among adolescents during 2021, vaccination coverage of at least 1 dose \n•89% for MenACWY\n•31% for MenB\n–Limited data are available on vaccine uptake in other individuals recommended to receive \nMenACWY or MenB vaccine\n▪Use of combination vaccines can reduce number of injections and is generally preferred over \nseparate injections of the equivalent component vaccines1,2\n13\n1 General Best Practice Guidelines for Immunization. Best Practice Guidance of the ACIP. https://www.cdc.gov/vaccines/hcp/acip -recs/general -recs/downloads/general -recs.pdf\n2 American Academy of Pediatrics. Red Book 2018. Report of the Committee on Infectious Diseases. 31stEd. https://seciss.facmed.unam.mx/wp -content/uploads/2021/02/Red -Book -31th -Edition.pdf15QuestionPICO 1 \nMenABCWY vs. MenACWY + MenBPICO 2 \nMenABCWY vs. MenACWYPICO 3 \nMenABCWY vs. Men B\nDoes the target population feel \nthat desirable effects are large \nrelative to undesirable effects?Probably yes Probably yesProbably yes or don’t \nknow\nImportant uncertainty or \nvariability in how much people \nvalue the main outcomes?Probably no Probably yes Probably yes \n16ACCEPTABILITY\nIs the intervention acceptable to key stakeholders?\n▪Limited data were available\n▪Acceptability likely depends on PICO and balance of stakeholder values\n–Health care providers likely supportive of options that allow stocking fewer vaccines1,2\n–Potential to increase vaccination rates against serogroup B disease\n–Reduces number of injections from 4 to 3 for some patients\n–Potential to incentivize MenB administration at age 16 years with waning immunity by peak risk for some \npatients\n•Many vaccine providers prefer waiting until closer to exposure to congregate settings (college/military)\n–Concerns about increasing exposure to MenB (which is more reactogenic than MenACWY ) when burden of \nMenB disease is already low despite low vaccine coverage\n•31% single dose\n•<12% second dose\n1CDC. Timing and Spacing of Immunobiologics : General Best Practice Guidelines for Immunization. ACIP Timing and Spacing Guidelines for Immunization | CDC . \n2Hall E, Odafe S, Madden J, Schillie S. Qualitative Conceptual Content Analysis of COVID -19 Vaccine Administration Error Inquiries. Vaccines . 2023; 11(2):254.16WG interpretationPICO 1 \nMenABCWY vs. MenACWY + MenBPICO 2 \nMenABCWY vs. MenACWYPICO 3 \nMenABCWY vs. Men B\nProbably yes or yes Probably yes or yes Don’t know\nRESOURCE USE\nIs the intervention a reasonable and efficient allocation of resources? \n▪All proposed meningococcal \nvaccine strategies are \nexpensive, including currently \nrecommended options for \nadolescents (QQ and QQBB)\n▪With new price estimates, QPP \nis the most cost -effective \noption when MenB protection \nis desired\n17WG interpretationPICO 1 \nMenABCWY vs. MenACWY + MenBPICO 2 \nMenABCWY vs. MenACWYPICO 3 \nMenABCWY vs. Men B\nProbably yes or yes Probably no or no Probably yes or yesStrategy Cost/person\nPublic sector QQ 241.2\nQQBB 554.88\nQPB 479.94\nQPP 465.6\nQQPP 586.2\nPrivate sector QQ 372.0\nQQBB 854.64\nQPB 707.32\nQPP 666.0\nQQPP 852.0\nEQUITY\nWhat would be the impact on health equity?\n▪Limited data were available \n▪The pentavalent vaccine is not expected to negatively impact equity\n▪It could potentially reduce disparities among those who might be interested in being \nvaccinated against serogroup B but who might not receive clinical care that includes \ndiscussion of the MenB vaccine \n▪Possible risk of clinics not stocking monovalent B vaccines with some policy options, which \ncould affect availability for \n–Outbreaks\n–People at increased risk recommended to receive 3 doses of MenB -FHbp\n18WG interpretationPICO 1 \nMenABCWY vs. MenACWY + MenBPICO 2 \nMenABCWY vs. MenACWYPICO 3 \nMenABCWY vs. Men B\nProbably no impact or variesProbably increased, varies, or \ndon’t knowDon’t know\nFEASIBILITY\nIs the intervention feasible to implement?\n▪Challenges with insurance coverage specific to the pentavalent vaccine not expected\n▪Substantial financial burdens for providers or health systems not expected\n▪Pentavalent vaccine would provide additional option in current schedule and may reduce \nnumber of doses for some people\n▪Administration requires reconstitution, which may lead to administration errors1\n▪Stocking three different meningococcal vaccine types may be prohibitive for some \nproviders\n▪Lack of B vaccines interchangeability complicates stocking considerations\n19WG \ninterpretationPICO 1 \nMenABCWY vs. MenACWY + MenBPICO 2 \nMenABCWY vs. MenACWYPICO 3 \nMenABCWY vs. Men B\nProbably yes or yes Probably yes or yes Probably yes or yes\n1https://www.cdc.gov/mmwr/volumes/65/wr/mm6506a4.htm\n20DomainPICO 1 \nMenABCWY vs. MenACWY + MenBPICO 2 \nMenABCWY vs. MenACWYPICO 3 \nMenABCWY vs. Men B\nPublic health problem Yes Yes Yes\nBenefits \n&\nharmsDesirable anticipated effects Small Minimal, small, or moderate Minimal\nUndesirable anticipated \neffectsSmall Minimal or small Minimal or small\nDesirable effects > undesirable \neffects?Favors interventionFavors intervention, comparison, or \nbothFavors intervention or comparison\nOverall certainty Varies by group Varies by group Varies by group\nValuesAre desirable effects large \nrelative to undesirable \neffects?Probably yes Probably yes Probably yes or don’t know\nImportant uncertainty or \nvariability?Probably no Probably yes Probably yes \nAcceptability Probably yes or yes Probably yes or yes Don’t know\nResource use Probably yes or yes Probably no or no Probably yes or yes\nEquity Probably no impact or variesProbably increased, varies, or don’t \nknowDon’t know\nFeasibility Probably yes or yes Probably yes or yes Probably yes or yesEtRsummary –all 3 PICOs\n20Favorable Somewhat favorable Uncertain Unfavorable\nSummary of work group consensus and \ndebate\n21▪Strong consensus in favor of PICO 1: MenABCWY as an option for MenACWY + MenB (QPB)\n▪Strong consensus a gainst PICO 2: MenABCWY as an option for MenACWY only (PPB )\n▪Limited consensus regarding PICO 3: MenABCWY as an option for MenB only\n▪Options debated for PICO 3\nOption Preference\nA Reject outright\nB Accept with limitations (i.e., QPP only)\nC Accept fully (i.e., QPP , QQPP , QQPB)\nQ\n11–12       16          17          18          19          20          21          22          23\nAge (years) BB\nQYes \n(age >16 \nyears)\n22Existing recommendations for routine schedule \nincorporating SCDM\nQBBYes \n(age 16 years)Serogroup B \nvaccine \ndesired based \non shared \nclinical \ndecision -\nmaking?\nNo\nQ\nQ\n11–12       16          17          18          19          20          21          22          23\nAge (years) BB\nQYes \n(age >16 \nyears)\n23QBBYes \n(age 16 years)Serogroup B \nvaccine \ndesired based \non shared \nclinical \ndecision -\nmaking?\nNo\nQPB\nB POption A adds QPB to the existing options\nLack of dataNeither option is consistent \nwith licensure (i.e., 2 -dose \nMenABCWY series)\nQ\n11–12       16          17          18          19          20          21          22          23\nAge (years) BB\nQYes \n(age >16 \nyears)\n24QBBYes \n(age 16 years)Serogroup B \nvaccine \ndesired based \non shared \nclinical \ndecision -\nmaking?\nNo\nQPB\nB POption B adds QPP to Option A\nPP\nQ\n11–12       16          17          18          19          20          21          22          23\nAge (years) BB\nQYes \n(age >16 \nyears)\n25QBBYes \n(age 16 years)Serogroup B \nvaccine \ndesired based \non shared \nclinical \ndecision -\nmaking?\nNo\nQPB\nB P Option C adds QQPP and QQPB to option B\nPPQQ PP\nPB•Higher cost \n•Lack of data\n26Summary of routine schedule interpretation \nfor 3 options \n26All options would permit current standard of care (i.e., QQ vs. QQBB under SCDM)\nOption* Preference for PICO 3 Schedule options incorporating \nSCDM for MenB\nA Reject outright QPB\nB Accept with limitations QPB + QPP\nC Accept fully QPB + QPP + QQPP + QQPB\n*All options include a recommendation in favor of PICO 1 and against PICO 2 \n27WG deliberations regarding 3 most favored options\nCONSIDERATIONOption A\nPICO 1 (QPB)Option B\nPICO 1 + PICO 3 (QPP only)Option C\nPICO 1 + PICO 3 (QPP , QQPP , QQPB)\nCLINICAL\nAlignment with clinical trial dataNot directly assessed; however, \nsecond pentavalent dose is \nprimarily for additional B \nprotectionDirectly assessed in clinical trial (6 -\nor 12 -month interval between \npentavalent doses)Options with additional antigenic \nexposures for which safety and \nimmunogenicity have not been assessed \n(QQPP , QQPB)\nAlignment with licensure Off-label Yes Yes\nExcess doses for ≥1 serogroup No Yes (1 dose) Yes (multiple doses)\nSTOCKING AND ADMINISTRATION\nFlexibility (especially for under -\nresourced clinics)Least Intermediate Most\nMinimum # vaccines to stock if using \nMenABCWY for routine indications*3 2 2\nECONOMIC\nProjected cost effectiveness Unclear cost effectiveness Most cost -effective option based \non recent price update from PfizerIncludes more expensive options not \nassessed in CE model (e.g., QQPP)\nPotential for insurance reimbursement \nissuesYes No No\nMost favorable Somewhat favorable Least favorable27*All options would require stocking 3 vaccines for special situations if using MenABCWY . Minimum number of vaccines to stock will remain 2 ( MenACWY , MenB ) if not using MenABCWY .\n28WG deliberations regarding 3 most favored options\nCONSIDERATIONOption A\nPICO 1 (QPB)Option B\nPICO 1 + PICO 3 (QPP only)Option C\nPICO 1 + PICO 3 (QPP , QQPP , QQPB)\nCLINICAL\nAlignment with clinical trial dataNot directly assessed; however, \nsecond pentavalent dose is \nprimarily for additional B \nprotectionDirectly assessed in clinical trial (6 -\nor 12 -month interval between \npentavalent doses)Options with additional antigenic \nexposures for which safety and \nimmunogenicity have not been assessed \n(QQPP , QQPB)\nAlignment with licensure Off-label Yes Yes\nExcess doses for ≥1 serogroup No Yes (1 dose) Yes (multiple doses)\nSTOCKING AND ADMINISTRATION\nFlexibility (especially for under -\nresourced clinics)Least Intermediate Most\nMinimum # vaccines to stock if using \nMenABCWY for routine indications*3 2 2\nECONOMIC\nProjected cost effectiveness Unclear cost effectiveness Most cost -effective option based \non recent price update from PfizerIncludes more expensive options not \nassessed in CE model (e.g., QQPP)\nPotential for insurance reimbursement \nissuesYes No No\nMost favorable Somewhat favorable Least favorable28*All options would require stocking 3 vaccines for special situations if using MenABCWY . Minimum number of vaccines to stock will remain 2 ( MenACWY , MenB ) if not using MenABCWY .\n29WG deliberations regarding 3 most favored options\nCONSIDERATIONOption A\nPICO 1 (QPB)Option B\nPICO 1 + PICO 3 (QPP only)Option C\nPICO 1 + PICO 3 (QPP , QQPP , QQPB)\nCLINICAL\nAlignment with clinical trial dataNot directly assessed; however, \nsecond pentavalent dose is \nprimarily for additional B \nprotectionDirectly assessed in clinical trial (6 -\nor 12 -month interval between \npentavalent doses)Options with additional antigenic \nexposures for which safety and \nimmunogenicity have not been assessed \n(QQPP , QQPB)\nAlignment with licensure Off-label Yes Yes\nExcess doses for ≥1 serogroup No Yes (1 dose) Yes (multiple doses)\nSTOCKING AND ADMINISTRATION\nFlexibility (especially for under -\nresourced clinics)Least Intermediate Most\nMinimum # vaccines to stock if using \nMenABCWY for routine indications*3 2 2\nECONOMIC\nProjected cost effectiveness Unclear cost effectiveness Most cost -effective option based \non recent price update from PfizerIncludes more expensive options not \nassessed in CE model (e.g., QQPP)\nPotential for insurance reimbursement \nissuesYes No No\nMost favorable Somewhat favorable Least favorable29*All options would require stocking 3 vaccines for special situations if using MenABCWY . Minimum number of vaccines to stock will remain 2 ( MenACWY , MenB ) if not using MenABCWY .\n30WG deliberations regarding 3 most favored options\nCONSIDERATIONOption A\nPICO 1 (QPB)Option B\nPICO 1 + PICO 3 (QPP only)Option C\nPICO 1 + PICO 3 (QPP , QQPP , QQPB)\nCLINICAL\nAlignment with clinical trial dataNot directly assessed; however, \nsecond pentavalent dose is \nprimarily for additional B \nprotectionDirectly assessed in clinical trial (6 -\nor 12 -month interval between \npentavalent doses)Options with additional antigenic \nexposures for which safety and \nimmunogenicity have not been assessed \n(QQPP , QQPB)\nAlignment with licensure Off-label Yes Yes\nExcess doses for ≥1 serogroup No Yes (1 dose) Yes (multiple doses)\nSTOCKING AND ADMINISTRATION\nFlexibility (especially for under -\nresourced clinics)Least Intermediate Most\nMinimum # vaccines to stock if using \nMenABCWY for routine indications*3 2 2\nECONOMIC\nProjected cost effectiveness Unclear cost effectiveness Most cost -effective option based \non recent price update from PfizerIncludes more expensive options not \nassessed in CE model (e.g., QQPP)\nPotential for insurance reimbursement \nissuesYes No No\nMost favorable Somewhat favorable Least favorable30*All options would require stocking 3 vaccines for special situations if using MenABCWY . Minimum number of vaccines to stock will remain 2 ( MenACWY , MenB ) if not using MenABCWY .\n31Balance of Consequences —PICO 1 \nMenABCWY as an option for MenACWY+MenB\nUndesirable \nconsequences  \nclearly outweigh \ndesirable \nconsequences in \nmost settings Undesirable \nconsequences \nprobably outweigh \ndesirable \nconsequences in \nmost settingsThe balance \nbetween  \ndesirable and \nundesirable \nconsequences is \nclosely balanced \nor uncertainDesirable \nconsequences  \nprobably outweigh \nundesirable \nconsequences in \nmost settingsDesirable \nconsequences \nclearly outweigh \nundesirable \nconsequences in \nmost settingsThere is \ninsufficient \nevidence to \ndetermine the \nbalance of \nconsequences\n31Majority of WG members think desirable consequences probably\nor clearly outweigh undesirable consequences in most settings\nMost common 2ndmost common 3rdmost common\n32 Most common 2ndmost commonWork Group Interpretation —PICO 1\nWe do not recommend the intervention, but it may be used within FDA licensed indications\nWe recommend the intervention for individuals based on shared clinical decision -making\nWe recommend the interventionShould the pentavalent vaccine be included as an option for \nMenACWY/MenB vaccination in people currently recommended to \nreceive both vaccines ?\n32Majority of WG members favored recommending the intervention\n33Balance of Consequences —PICO 2 \nMenABCWY as an option for MenACWY\nUndesirable \nconsequences  \nclearly outweigh \ndesirable \nconsequences in \nmost settings Undesirable \nconsequences \nprobably outweigh \ndesirable \nconsequences in \nmost settingsThe balance \nbetween  \ndesirable and \nundesirable \nconsequences is \nclosely balanced \nor uncertain Desirable \nconsequences  \nprobably outweigh \nundesirable \nconsequences in \nmost settingsDesirable \nconsequences \nclearly outweigh \nundesirable \nconsequences in \nmost settingsThere is \ninsufficient \nevidence to \ndetermine the \nbalance of \nconsequences\n33 Most common 2ndmost common 3rdmost commonMajority of WG members think undesirable consequences probably or \nclearly outweigh desirable consequences in most settings\n34Work Group Interpretation —PICO 2\nWe do not recommend the intervention, but it may be used within FDA licensed indications\nWe recommend the intervention for individuals based on shared clinical decision -making\nWe recommend the interventionShould the pentavalent vaccine be included as an option for \npeople currently recommended to receive MenACWY only ? \n34Most common 2ndmost commonMajority of WG members favored not recommending the intervention\n35 Most common 2ndmost commonBalance of Consequences —PICO 3 \nMenABCWY as an option for MenB\nUndesirable \nconsequences  \nclearly outweigh \ndesirable \nconsequences in \nmost settings Undesirable \nconsequences \nprobably outweigh \ndesirable \nconsequences in \nmost settingsThe balance \nbetween  \ndesirable and \nundesirable \nconsequences is \nclosely balanced \nor uncertain Desirable \nconsequences  \nprobably outweigh \nundesirable \nconsequences in \nmost settings Desirable \nconsequences \nclearly outweigh \nundesirable \nconsequences in \nmost settings There is \ninsufficient \nevidence to \ndetermine the \nbalance of \nconsequences\n35The WG did not reach a majority consensus on the balance of \nconsequences\n36Work Group Interpretation —PICO 3\nWe do not recommend the intervention, but it may be used within FDA licensed indications\nWe recommend the intervention for individuals based on shared clinical decision -making\nWe recommend the intervention but only in certain circumstances (i.e., QPP)\nWe recommend the intervention in all circumstancesShould the pentavalent vaccine be included as an option for \npeople currently recommended to receive MenB only ? \n36Added an additional option because some WG members favored QPP only\n37Work Group Interpretation —PICO 3\nWe do not recommend the intervention, but it may be used within FDA licensed indications\nWe recommend the intervention for individuals based on shared clinical decision -making\nWe recommend the intervention but only in certain circumstances (i.e., QPP)\nWe recommend the intervention in all circumstancesShould the pentavalent vaccine be included as an option for \npeople currently recommended to receive MenB only ? \n▪WG was divided regarding PICO 3\n▪Majority favored PICO 3 in some form\n▪Substantial minority of work group members favored not recommending the intervention\n37Most common 2ndmost common 3rdmost common 4thmost common\n3838PICO 1 (QPB)\nPICO 2 (PPB)\nPICO 3 (QPP only)\nPfizer’s MenABCWY vaccine may be used when both MenACWY and MenB are indicated at the \nsame visit.* If MenABCWY is administered in this way, a second dose of MenABCWY may be \nadministered 6 months later to complete the series.\n*1) Healthy individuals aged 16 –23 years (routine schedule) when shared clinical decision -\nmaking favors administration of MenB vaccination, 2) individuals aged 10 years and older at \nincreased risk of meningococcal disease (e.g., due to persistent complement deficiencies, \ncomplement inhibitor use, or functional or anatomic asplenia) due for both vaccines. \n▪Remarks:\n•for Pfizer’s MenABCWY vaccine, data are not available regarding safety or immunogenicity of dosing intervals exceeding \n12 months\n•the licensed B component vaccines are not interchangeable by manufacturer. Administration of a B component vaccine \n(MenB or MenABCWY ) requires that subsequent B component vaccine doses be from the same manufacturer\n•the minimum interval for Pfizer’s MenABCWY vaccine is 6 months. Individuals at increased risk of meningococcal disease \nwho are recommended to receive additional doses of MenACWY and MenB less than 6 months after a dose of \npentavalent meningococcal vaccine should instead receive separate MenACWY and MenB -FHbp vaccines\nCombined draft proposal for option B\n39Rationale in favor of combined draft proposal\n▪Aligns with clinical trial data and licensure\n▪Allows for f ewer injections than QQBB\n▪Provides flexibility with vaccine inventory, including for clinics that prefer to stock \n2 vaccines for routine indications\n▪Stocking fewer vaccines may increase equity (e.g., if under -resourced clinics are \nless likely to stock 3 vaccines )\n▪Most cost -effective option based on recent price update from Pfizer\n39\n40Rationale against combined draft proposal\n▪Unnecessary ACWY antigen exposure for second pentavalent dose in routine schedule \n(i.e., when only MenB is indicated)\n▪Not as much flexibility for providers as Option 3\nGeneral considerations (all options):\n▪Potential to incentivize MenB at age 16 years with waning immunity by peak risk (i.e., \ncollege/military) for some patients \n▪Uncertainty regarding cost estimates\n▪If using MenABCWY , it will be necessary to stock 3 vaccines to cover all indications \n(routine schedule + special situations), which may be challenging for some vaccine \nproviders \n40\nAcknowledgments\n▪ ACIP Members on the WG\n– Kathy Poehling (Chair)\n– Lynn Bahta\n– Jamie Loehr\n▪ Ex Officio WG Members\n– Margaret Bash (FDA)\n– Mark Connelly (FDA)\n– Francisco Leyva (NIH)\n▪ WG Liaisons and Consultants\n– Amra Resic (AAFP)\n– Samir Shah (AAP) \n– Sharon McMullen (ACHA)\n– Cacky Tate / Karyn Lyons (AIM)\n– Paul Cieslak (CSTE)\n– Kathy Hsu (IDSA)\n– Joseline Zafack (NACI)\n– Jeff Goad (NFID)\n– Jessica Cataldi (PIDS)\n– Amy Middleman (SAHM)\n– David Stephens (Emory)▪ CDC Contributors\n– Sam Crowe (DBD/NCIRD)\n– Lucy McNamara (DBD/NCIRD)\n– Ismael Ortega -Sanchez (DVD/NCIRD)\n– Andrew Leidner (ISD/NCIRD)\n– LeAnne Fox (DBD/NCIRD)\n– Susan Hariri (DBD/NCIRD)\n– Amy Rubis (DBD/NCIRD)\n– Noele Nelson (DBD/NCIRD)\n– Alison Albert (DBD/NCIRD)\n– Angela Jiles (DBD/NCIRD)\n– Jonathan Duffy (DHQP/NCEZID)\n– Tanya Myers (DHQP/NCEZID) \n– Liz Velazquez (ISD/NCIRD)\n– Jessica MacNeil (ACIP Secretariat)\n– Melinda Wharton (ACIP Secretariat)\n▪ GRADE/EtR Support\n– Doug Campos -Outcalt (Arizona)\n– Rebecca Morgan (Case Western Reserve)\n41\nThank you! \nQuestions?", "summary": "Summary of EtRand proposed  recommendations for Pfizer’s MenABCWY vaccine  Jennifer Collins MD, MSc Interim Co -Lead, ACIP Meningococcal Vaccines Work Group October 25, 2023National Center for Immunization & Respiratory Diseases ACIP Recommendations for Meningococcal Vaccines ▪ Routine schedule  –MenACWY : dose 1 at age 11 –12 years, booster dose at age 16 years –MenB (shared clinical decision -making): two doses at age 16–23 years (preferred age 16 –18 years) ▪ Special situations…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-25-26-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-10-25-26/04-Meningococcal-Collins-508.pdf", "doc_date": "2023-10-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 42}
{"title": "01 MPOX Sanchez 508", "content": "National Center for Emerging and Zoonotic Infectiou s Diseases \nMpox Vaccine Work Group:  Introduction \nACIP Meeting October 25, 2023 Pablo Sanchez MD /uni00YJhe Ohio State /uni00YYni/uni00-6ersit/uni00-9/uni2212Na/gJ1Yon/uni00--ide Children/uni2019s /uni00J8osp ital \nChair, ACIP Mpox Work Group \nGlobal mpox outbreak, 2022 \nFirst case in this outbreak identified in the Unite d Kingdom in May 2022 \nPrimarily affecting gay, bisexual, and other men wh o have sex with men \n(MSM) \nAssociated with person-to-person spread via close s kin-to-skin contact \nincluding sex \nDeaths have occurred, primarily among persons with severe \nimmunocompromise from advanced HIV \nU.S. case counts and deaths comprising 1/3 of cases  and deaths \n–>30,800 cases \n–54 deaths \nCurrent global cases reported to WHO, September, 2023 \nhttps://worldhealthorg.shinyapps.io/mpx_global/ \nJYNNEOS \nComprised of replication-deficient vaccinia virus \nAdministered subcutaneously* via 2 vaccine doses, 28 day s apart \nEffectiveness assessed by comparing immunologic response  to that for \nACAM2000 \nLicensed for prevention of both smallpox and mpox \nIs recommended for persons with HIV and other immunoc ompromising \nconditions \nLicensed for persons ≥ 18 years of age; an NIH trial is  underway to evaluate \nsafety and immunogenicity for persons 12-17 years of a ge \n*During the 2022 mpox outbreak, it was also administ ered intradermally because of limited vaccine avail ability; it is currently available \nin enough supply \nOutbreak recommendation: February and June ACIP meetings \nVote: ACIP recommends the 2-dose* JYNNEOS vaccine s eries for \npersons aged 18 years and older at risk of mpox during  an mpox \noutbreak † \n*Dose 2 administered one month after dose 1 †Public health authorities determine whether there i s an mpox outbreak; a single case may be considered an \nmpox outbreak at the discretion of public health aut horities. Other circumstances in which a public hea lth \nresponse may be indicated including ongoing risk of  introduction of mpox into a community due to diseas e \nactivity in another geographic area \nOutbreak recommendations intended for any U.S. mpox outbreak, \nregardless of whether associated with male-to-male sexual contact \nClinical guidance, including about use of vaccine i n children during \noutbreaks discussed \nNational mpox vaccination strategy for pre-exposure \nvaccination during current outbreak* \n*https://www.cdc.gov/poxvirus/monkeypox/interim-con siderations/overview.html Vaccination before exposure to mpox virus \n-Gay, bisexual, and other MSM, transgender or nonbi nary people (including adolescents \nwho fall into the aforementioned categories) who in  the past 6 months have had: \n•New diagnosis of ≥ 1 sexually transmitted disease \n•More than one sex partner \n-People with the following in the last 6 months: •Sex at commercial sex venue \n•Sex in association with large public event in geogr aphic area where mpox transmission \nis occurring \n-Sexual partners of people with the above risks -People who anticipate experiencing above risks -People with HIV or other causes of immunosuppressi on who have had recent or \nanticipate potential mpox exposure \nElimination of human-to-human transmission \nWHO strategy in development; additional resources a nd data needed \nImmunization may be one component of the strategy \nElimination is a complex issue not addressed by WG;  however, a \nrecommendation that persons at-risk for mpox during the ongoing \noutbreak receive the vaccines if they have not alre ady, may support any \nupcoming WHO strategy \nRecommendation that will be proposed during today’s  \nmeeting \nACIP recommends vaccination* with the 2-dose †JYNNEOS vaccine series for \npersons aged 18 years and older at risk for mpox §?\n*Interim recommendation to be revisited in 2-3 year s \n† Dose 2 administered 28 days after dose 1 \n§Persons at risk: \n•Gay, bisexual, and other men who have sex with men,  transgender or nonbinary people who \nin the past 6 months have had one of the following:\n•A new diagnosis of ≥ 1 sexually transmitted disease  \n•More than one sex partner \n•Sex at a commercial sex venue \n•Sex in association with a large public event in a g eographic area where mpox \ntransmission is occurring \n•Sexual partners of persons with the risks described  in above \n•Persons who anticipate experiencing any of the abov e \nPotential implications of interim routine recommendation \nIncrease vaccine coverage and prevent or minimize o utbreaks \nRemove some stigma and facilitate 1:1 consultation with clinician during \nappointments \nPotential commercialization of JYNNEOS \nProduct sponsor (Bavarian Nordic) has indicated they will attempt to \ncommercialize the vaccine if it is on a routine schedule \nThis will transition vaccine from U.S. government stockpiles  (which were \nintended for smallpox preparedness) to the commercial se ctor \nTentative timeline for ACIP discussions and votes* \nInterim routine recommendation and clinical guidance \nOctober 2023 Early 2024 Possibly 2024 Publication of 2 MMWRs: 1) Use of JYNNEOS during mpox \noutbreaks \n2) Use of JYNNEOS among \npersons at risk during the ongoing mpox outbreak Consider results from NIH trial about use of JYNNEOS in persons aged 12-18 years \n*February 2023 and June 2023 votes do not impact ex isting recommendations for the current mpox outbrea k. \n8uni0067https://www.cdc.gov/poxvirus/monkeypox/interim-cons iderations/overview.html TBD Review epidemiology, cost-effectiveness analysis, and other data to determine if routine recommendation should be continued \nProposed recommendation \nACIP recommends vaccination* with the 2-dose †JYNNEOS vaccine series for \npersons aged 18 years and older at risk for mpox §?\n*Interim recommendation to be revisited in 2-3 year s \n† Dose 2 administered 28 days after dose 1 \n§Persons at risk: \n•Gay, bisexual, and other men who have sex with men,  transgender or nonbinary people who \nin the past 6 months have had one of the following:\n•A new diagnosis of ≥ 1 sexually transmitted disease  \n•More than one sex partner \n•Sex at a commercial sex venue \n•Sex in association with a large public event in a g eographic area where mpox \ntransmission is occurring \n•Sexual partners of persons with the risks described  in above \n•Persons who anticipate experiencing any of the abov e \nGoal for today’s meeting \nUpdates from the ongoing outbreak \n–Epidemiology:  Dr. Faisal Minhaj \n–Evidence to recommendations framework:  Dr. Agam Ra o \n–Clinical guidance and next steps:  Dr. Agam Rao \nVote \n–Mpox vote \n–Mpox Vaccines for Children vote \nWG members \nACIP Member \nPablo Sánchez Beth Bell \nEx Officio and Liaison Members \nCSTE: Chris Hahn / Paul Cieslak \nASTHO: Ericka McGowan \nNACHO: Philip Huang FDA: Sixun Yang, Clement \nMeseda & Alonzo García \nACOG: Howard Minkoff AAP: Jim Campbell \nHRSA:  Vikram Krishnasamy AIM: Rob Schechter / Jane Zucker APHL:  Jafar Razeq \nNIH: Janet Lathey / Kimberly Taylor IHS: Matthew Clark NACI: Nicole Forbes / Joshua Montroy IDSA: Shireesha Dhanireddy / Rajesh Gandhi \nInvited Consultants \nSubject matter experts: Inger Damon, Stuart Isaacs, Mike Merchlinsky & Amanda \nZarrabian (HHS/BARDA) \nClinician experts in STIs, HIV, pediatrics, maternal vaccination, vaccine safety, health equity, smallpox vaccination strategies, occupational health \nClinician experts \nSTIs, HIV, and mpox \n(adult and peds): \nJason Zucker \nPablo Tebas Vince Marconi Kim Workowski Bonnie Maldonado \nImmunizations (including for special \npopulations) and vaccine safety: \nRuth Karron Flor Munoz-Rivas Kathy Edwards Health equity, vaccination strategies \nincluding for smallpox: \nJoel Breman \nGerard Vong \nOccupational Medicine and worker safety: \nMark Russi \nCDC contributors \nMpox epi, lab, and vaccine experts \nAndrea McCollum \nChristy Hutson Sathesh Panayampalli \nInfection control, worker safety: \nMarie de Perio David Kuhar Vaccine safety \nJonathan Duffy \nMichael McNeil Regulatory Affairs \nYon Yu \nSTIs and HIV \nLaura Bachmann Leandro Mena \nJohn Brooks Alexa Oster Drug Services \nJulian Jolly \nVaccine \nimplementation \nLaura Daniel \nJames Lee \nDoD Liaison to CDC \nAlan Lam \nWork group lead  \nAgam Rao \nFor more information, contact CDC 1-800-CDC-INFO (232-4636) TTY:  1-888-232-6348    www.cdc.gov The findings and conclusions in this report are tho se of the authors and do not necessarily represent the \nofficial position of the Centers for Disease Contro l and Prevention. Thank you!", "summary": "National Center for Emerging and Zoonotic Infectiou s Diseases  Mpox Vaccine Work Group:  Introduction  ACIP Meeting October 25, 2023 Pablo Sanchez MD /uni00YJhe Ohio State /uni00YYni/uni00-6ersit/uni00-9/uni2212Na/gJ1Yon/uni00--ide Children/uni2019s /uni00J8osp ital  Chair, ACIP Mpox Work Group  Global mpox outbreak, 2022  First case in this outbreak identified in the Unite d Kingdom in May 2022  Primarily affecting gay, bisexual, and other men wh o have sex with men  (MSM)  Associated…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-25-26-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-10-25-26/01-MPOX-Sanchez-508.pdf", "doc_date": "2023-10-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 17}
{"title": "02 MPOX Minhaj 508", "content": "National Center for Emerging and Zoonotic Infectiou s Diseases \n2022/2023 Mpox Outbreak: Situational Awareness and Updates \nACIP Meeting October 25, 2023 Faisal Syed Minhaj, PharmD, MPH, DABAT Epidemiologist \nPoxvirus and Rabies Branch Division of High Consequence Pathogens and Patholog y \nUnited States Mpox Case Counts May 2022–Sept 28, 202 3 \nhttps://www.cdc.gov/poxvirus/mpox/response/2022/mpx -trends.html /uni004D/uni0061/uni0079/uni002D/uni0032/uni0033\n/uni004A/uni0075/uni006E/uni002D/uni0036\n/uni004A/uni0075/uni006E/uni002D/uni0032/uni0030\n/uni004A/uni0075/uni006C/uni002D/uni0034\n/uni004A/uni0075\n/uni006C/uni002D/uni0031/uni0038/uni0041/uni0075/uni0067/uni002D/uni0031\n/uni0041/uni0075\n/uni0067/uni002D/uni0031/uni0035/uni0041/uni0075\n/uni0067/uni002D/uni0032/uni0039/uni0053/uni0065\n/uni0070/uni002D/uni0031/uni0032/uni0053/uni0065\n/uni0070/uni002D/uni0032/uni0036/uni004F/uni0063/uni0074/uni002D/uni0031/uni0030\n/uni004F/uni0063/uni0074\n/uni002D/uni0032/uni0034/uni004E/uni006F/uni0076/uni002D\n/uni0037/uni004E/uni006F/uni0076/uni002D/uni0032/uni0031\n/uni0044/uni0065\n/uni0063/uni002D/uni0035/uni0044/uni0065/uni0063\n/uni002D/uni0031/uni0039/uni004A/uni0061/uni006E/uni002D/uni0032\n/uni004A/uni0061/uni006E/uni002D/uni0031/uni0036\n/uni004A/uni0061/uni006E/uni002D/uni0033/uni0030\n/uni0046/uni0065/uni0062/uni002D/uni0031/uni0033\n/uni0046/uni0065/uni0062/uni002D/uni0032/uni0037\n/uni004D/uni0061/uni0072\n/uni002D/uni0031/uni0033/uni004D/uni0061/uni0072\n/uni002D/uni0032/uni0037/uni0041/uni0070/uni0072/uni002D/uni0031/uni0030\n/uni0041/uni0070/uni0072/uni002D/uni0032/uni0034\n/uni004D/uni0061/uni0079/uni002D/uni0038\n/uni004D/uni0061/uni0079/uni002D/uni0032/uni0032\n/uni004A/uni0075/uni006E/uni002D/uni0035\n/uni004A/uni0075/uni006E/uni002D/uni0031/uni0039\n/uni004A/uni0075/uni006C/uni002D/uni0033\n/uni004A/uni0075/uni006C/uni002D/uni0031/uni0037/uni004A/uni0075/uni006C/uni002D/uni0033/uni0031/uni0041/uni0075\n/uni0067/uni002D/uni0031/uni0034/uni0041/uni0075/uni0067/uni002D\n/uni0032/uni0038/uni0053/uni0065\n/uni0070/uni002D/uni0031/uni0031/uni0053/uni0065/uni0070/uni002D/uni0032/uni0035/uni0030/uni0031/uni0030/uni0030 /uni0032/uni0030/uni0030 /uni0033/uni0030/uni0030 /uni0034/uni0030/uni0030 /uni0035/uni0030/uni0030 /uni0036/uni0030/uni0030 /uni0037/uni0030/uni0030 /uni0043/uni0061/uni0073/uni0065/uni0020/uni0020/uni0043/uni006F/uni0075/uni006E/uni0074/uni0037/uni002D/uni0064/uni0061/uni0079/uni0020/uni0041/uni0076/uni0065/uni0072/uni0061/uni0067/uni0065 \n/uni0032/uni0030/uni0032/uni0032 /uni0032/uni0030/uni0032/uni0033 \nSubject to reporting irregularities Subject to reporting irregularities N = 30,681 \nUnited States Mpox Case Counts Jan 1–Sept 28, 2023 \nhttps://www.cdc.gov/poxvirus/mpox/response/2022/mpx -trends.html \nN = 785 \nSubject to reporting irregularities 7-day average of daily cases reported \nUnited States Mpox Case Counts Jan 1–Sept 28, 2023 \nhttps://www.cdc.gov/poxvirus/mpox/response/2022/mpx -trends.html \nSubject to reporting irregularities 5–7\nN = 785 \n7-day average of daily cases reported \nX7-day daily average case range \nUnited States Mpox Case Counts Jan 1–Sept 28, 2023 \nhttps://www.cdc.gov/poxvirus/mpox/response/2022/mpx -trends.html \nSubject to reporting irregularities 5–7 1–3\nN = 785 \n7-day average of daily cases reported \nX7-day daily average case range \nUnited States Mpox Case Counts Jan 1–Sept 28, 2023 \nhttps://www.cdc.gov/poxvirus/mpox/response/2022/mpx -trends.html \nSubject to reporting irregularities 5–7 2–5 1–3\nN = 785 \n7-day average of daily cases reported \nX7-day daily average case range \nUnited States Mpox Case Counts Jan 1–Sept 28, 2023 \nhttps://www.cdc.gov/poxvirus/mpox/response/2022/mpx -trends.html \nSubject to reporting irregularities 5–7 2–5 1–3 1–4\nN = 785 \n7-day average of daily cases reported \nX\n7-day daily average case range \nCases Following Vaccination \nReported since the outbreak started, including clusters \nGenerally, most have had mild illness \n–Few requiring hospitalization \n–Many did not need any treatment \n–Low number of lesions \nHazra A. Lancet Infect Dis . 2023 Sep 4:S1473-3099(23)00492-9. \n\nMpox Reinfection \nPotential reinfection cases have been published in the literature, but only a few with convincing evidence of true reinfection \nCDC is aware of <10 cases of probable reinfection \nProbable reinfection cases seem to be milder than initial infection \nHazra A. Lancet Infect Dis . 2023 Sep 4:S1473-3099(23)00492-9. \n\nCDC Continues to Consult on Severe Mpox Cases and \nDeaths \nhttps://www.cdc.gov/mmwr/volumes/71/wr/mm7144e1.htmCDC’s mpox clinical consult service continues to consult on  2-6 new cases \nmonthly over the last 6 months \nRepeat consultations are more frequent, and include seve re cases with \ninfections ongoing for months \n54 people have died from mpox in the United States since  May 2022, with 2 \njust this September \nBlack persons, people living with HIV (mostly advanced HIV  [AIDS]), and people \nexperiencing homelessness are disproportionately affected\nMpox Cases Reported to CDC by Age and Gender May 17, 2022–Sept 28, 2023 \nhttps://www.cdc.gov/poxvirus/mpox/response/2022/dem ographics.html Data were available for /uni200999.4% \nof cases reported to CDC \nMpox Cases Reported to CDC by Race and Ethnicity May 17, 2022–Jun 14, 2023 \n57     1095   9233 10965  4739  1748   686     297    159      61       57       43       90      108    105     82        21 Count within columns \nhttps://www.cdc.gov/poxvirus/mpox/response/2022/dem ographics.html Subject to reporting irregularities \nData were available for /uni200994.5% \nof cases reported to CDC \n\nMpox Cases Globally Apr–Sept 2023 \n15 \n\nhttps://worldhealthorg.shinyapps.io/mpx_global/ \nFirst and Second Doses of JYNNEOS Vaccine /uni0041d/uni006Dinistra/g415ons/uni2212/uni0055nited States/uni002C /uni004Da/uni0079 /uni0032/uni0030/uni0032/uni0032/uni2212Se/uni0070t /uni0032/uni0030/uni0032/uni0033 \nOverall vaccine coverage* \n1-dose: 38.8% and 2-dose: 24.3% \n*Coverage is the estimated proportion who have recei ved vaccination divided by the population recommend ed to receive the vaccine,which is estimated \nusing 2021 data for MSM with HIV pre-exposure proph ylaxis (PrEP) indications and 2020 data for HIV pre valence among MSM from CDC AtlasPlus . These \nestimates are increased by 25% to account for addit ional vaccine eligible people not captured by these  data sources totaling approximately 2 million peop le.\nShift in Vaccine Administration Sites From Public Health Clinics to Medical Centers \n•Public health providers administered 40% of all vaccines through Mar 2023 \n•Medical care providers administered an increasing proportion of vaccines since the start of the outbreak \n•Pharmacies consistently provided 3-4% of all vaccines \nPublic Health \nProvider or \nClinic Medical \nCenter \nProvider Commercial \nVaccination \nService \nProvider Pharmacy Other Percentage of Doses Administered \nCategories of Medical Providers Administering Vaccin es \nFrom 2022 to 2023, there were statistically significant increases in vaccines provided by •Primary care offices \n•Federally qualifying health centers (FQHC) \n•Other health centers \nPrimary \nCare Hospital FQHC Health \nCenter -\nOther Health \nCenter -\nSTD/HIV Percentage of Doses Administered \nModeling \nEstimating Averted Cases from Vaccination and Behavioral Adaptation in DC \nhttps://www.medrxiv.org/content/10.1101/2023.02.10. 23285772v1.full.pdf \nLines and shaded regions reflect median and interqu artile range from 120 simulations \nEstimated prevalent infections over time with no vaccination or behavioral adaptation. \nEstimating Averted Cases from Vaccination and Behavioral Adaptation in DC \nhttps://www.medrxiv.org/content/10.1101/2023.02.10. 23285772v1.full.pdf \nLines and shaded regions reflect median and interqu artile range from 120 simulations \nBehavioral adaptation alone would have had early impact on the curve and flattened it \nEstimating Averted Cases from Vaccination and Behavioral Adaptation in DC \nhttps://www.medrxiv.org/content/10.1101/2023.02.10. 23285772v1.full.pdf Lines and shaded regions reflect median and interqu artile range from 120 simulations \nBehavioral adaptation alone would have had early impact on the curve and flattened it \nVaccination alone would have had a later impact, but would have ended the outbreak within 1 year\nEstimating Averted Cases from Vaccination and Behavioral Adaptation in DC \nhttps://www.medrxiv.org/content/10.1101/2023.02.10. 23285772v1.full.pdf Lines and shaded regions reflect median and interqu artile range from 120 simulations \nBehavioral adaptation alone would have had early impact on the curve and flattened it \nVaccination alone would have had a later impact, but would have ended the outbreak within 1 year\nCombined, behavioral adaptation and vaccination averted 80% of cases 1 year into the outbreak \nRisk for Recurrent Mpox Outbreak Lasting >3 Months, by Immunity Level — United States, 2023 \nPollock ED. MMWR MorbMortal WklyRep 2023;72:568–573 .% Risk of \nRecurrence \n% Population at increased mpox risk with partial or  full immunity Risk of recurrence increases linearly as the percent of the high-risk population with full or partial protection decreases\nCumulative Monkeypox virus I nfections Relative to \n2022, by Immunity Level — United States, 2023 \nPollock ED. MMWR MorbMortal WklyRep 2023;72:568–573 .Cumulative \nmonkeypox \nvirus infections, \nrelative to 2022 \n% Population at increased mpox risk with partial or  full immunity \nCumulative Monkeypox virus I nfections Relative to \n2022, by Immunity Level — United States, 2023 \nPollock ED. MMWR MorbMortal WklyRep 2023;72:568–573 .>50% is needed to \nsignificantly decrease \nthe risk of large \noutbreaks Cumulative \nmonkeypox \nvirus infections, \nrelative to 2022 \n% Population at increased mpox risk with partial or  full immunity \nVaccine: Effectiveness and Safety Updates \nVaccine effectiveness of JYNNEOS against mpox ranges  from 36%–75% \nfor 1-dose vaccination and 66%–89% for 2-dose vaccination \nCases Controls Adjusted* VE (95% CI) \n1-dose JYNNEOS \nEpic Cosmos case-control study 146 1000 36% (22–47) \nMulti-jurisdictional case-control study 58 237 75% (61–84) \nNew York State case-control study 10 23 68% (25–86) \n.\n2-dose JYNNEOS \nEpic Cosmos case-control study 25 335 66% (47–78) \nMulti-jurisdictional case-control study 14 122 86% (74–89) \nNew York State case-control study 2 19 89% (44–98) \nVaccine Effectiveness (%) 0 20 40 60 80 100 \nVaccine effectiveness of JYNNEOS against mpox ranges  from 36%–75% \nfor 1-dose vaccination and 66%–89% for 2-dose vaccination \nCases Controls Adjusted* VE (95% CI) \n1-dose JYNNEOS \nEpic Cosmos case-control study 146 1000 36% (22–47) \nMulti-jurisdictional case-control study 58 237 75% (61–84) \nNew York State case-control study 10 23 68% (25–86) \n.\n2-dose JYNNEOS \nEpic Cosmos case-control study 25 335 66% (47–78) \nMulti-jurisdictional case-control study 14 122 86% (74–89) \nNew York State case-control study 2 19 89% (44–98) \nVaccine Effectiveness (%) 0 20 40 60 80 100 \nVaccine effectiveness of JYNNEOS against mpox ranges  from 36%–75% \nfor 1-dose vaccination and 66%–89% for 2-dose vaccination \nCases Controls Adjusted* VE (95% CI) \n1-dose JYNNEOS \nEpic Cosmos case-control study 146 1000 36% (22–47) \nMulti-jurisdictional case-control study 58 237 75% (61–84) \nNew York State case-control study 10 23 68% (25–86) \n.\n2-dose JYNNEOS \nEpic Cosmos case-control study 25 335 66% (47–78) \nMulti-jurisdictional case-control study 14 122 86% (74–89) \nNew York State case-control study 2 19 89% (44–98) \nVaccine Effectiveness (%) 0 20 40 60 80 100 \nMulti-jurisdictional Case-Control Study: Methods \n–Population: Men who have sex with men; ages 18-49; 12 U.S. juri sdictions \n–Time Period: August 19, 2022, to September 27, 2023 \n–Methods: \n–Cases identified from jurisdictions’ probable and confirm ed mpox case lists \n–Controls identified from healthcare settings providing HIV P rEP or sexually \ntransmitted infection (STI) clinics \n–Demographics, immunocompromised status, exposure hi story, and \nvaccination history collected using electronic surv eys \n–Vaccination status confirmed by state immunization registries \n–Analysis: \n–VE estimated using conditional logistic regression \n–Adjusted for age, race/ethnicity, immunocompromising conditions \n–Stratified by route of administration and immunocompromised statu s \nBoth partial and full vaccination with JYNNEOS showed \neffectiveness against mpox, regardless of administr ation \nroute \n*Adjusted for age, race/ethnicity, immunocompromise d status, reported close contact with a \nconfirmed/suspected mpox case in 3 weeks prior to i ndex event \nBoth partial and full vaccination with JYNNEOS showed \neffectiveness against mpox, regardless of administr ation \nroute \n*Adjusted for age, race/ethnicity, immunocompromise d status, reported close contact with a \nconfirmed/suspected mpox case in 3 weeks prior to i ndex event \nVE trended higher for immunocompetent participants \ncompared to self-reported immunocompromised \nparticipants \n*Adjusted for age, race/ethnicity, immunocompromise d status, reported close contact with a \nconfirmed/suspected mpox case in 3 weeks prior to i ndex event \n Confidence interval remains very wide \n More work is needed to understand VE in objectively confirmed immunocompromised people \nJYNNEOS Vaccine Safety Monitoring \nCDC vaccine safety monitoring is ongoing using two surveillance systems: \n–Vaccine Adverse Event Reporting System (VAERS) \n–Vaccine Safety Datalink (VSD) \nV-safe data collection for mpox vaccines was availa ble from \nNovember 2022 through March 21, 2023 \nJYNNEOS Vaccine Safety Findings Summary \n90% of VAERS reports were submitted in 2022 \nThe adverse events most commonly reported to VAERS h ave been injection \nsite symptoms (redness, swelling, pain, itching) \nMyocarditis and pericarditis are adverse events of specia l interest \n–Observed rates are consistent with expected backgroun d rates \nJYNNEOS Vaccine Safety Conclusions \nVAERS and VSD data do not suggest an increased risk f or myocarditis or \npericarditis following JYNNEOS, but the possibility of a small risk cannot be \nexcluded \nThe frequencies of local and systemic reactions reported  to v-safe after \nmpox vaccine were similar to those reported in clinical trials\nNo new or unexpected safety concerns have been ident ified \nSummary \nMpox cases and deaths continue to be reported domest ically and globally \nNeed to improve our overall vaccine coverage; <25% of t he eligible \npopulation is fully vaccinated with 2 doses \nModeling suggests that without vaccination, transmission o f mpox will \ncontinue with sporadic outbreaks \nNo new safety signals from VAERS or VSD \nVE appears stable for immunocompetent people \nAcknowledgements \nSarah Guagliardo \nAgam Rao \nRosalind Carter \nAndrea McCollum \nIan Kracalik \nAllie Tuttle \nJonathan Duffy \nEunice Kimunai \nKatrina Byrd Victoria Shelus \nChristine Hughes \nChristina Hutson \nIan Spicknall \nPatrick Clay \nEmily Pollock \nFor more information, contact CDC 1-800-CDC-INFO (232-4636) TTY:  1-888-232-6348    www.cdc.gov The findings and conclusions in this report are tho se of the authors and do not necessarily represent the \nofficial position of the Centers for Disease Contro l and Prevention. \nNational Center for Emerging and Zoonotic Infectiou s Diseases \nDivision of High-Consequence Pathogens and Patholog y Questions?", "summary": "National Center for Emerging and Zoonotic Infectiou s Diseases  2022/2023 Mpox Outbreak: Situational Awareness and Updates  ACIP Meeting October 25, 2023 Faisal Syed Minhaj, PharmD, MPH, DABAT Epidemiologist  Poxvirus and Rabies Branch Division of High Consequence Pathogens and Patholog y  United States Mpox Case Counts May 2022–Sept 28, 202 3  https://www.cdc.gov/poxvirus/mpox/response/2022/mpx -trends.html /uni004D/uni0061/uni0079/uni002D/uni0032/uni0033…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-25-26-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-10-25-26/02-MPOX-Minhaj-508.pdf", "doc_date": "2023-10-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 40}
{"title": "03 MPOX Rao 508", "content": "National Center for Emerging and Zoonotic Infectiou s Diseases \nEvidence to Recommendations Framework:  Vaccination with JYNNEOS for Persons At Risk of Mpo x \nAdvisory Committee on Immunization Practices October 25, 2023 Agam Rao, MD CAPT, US Public Health Service Poxvirus and Rabies Branch Centers for Disease Control and Prevention \nEvidence to Recommendations (EtR) Framework \nStructure to describe information considered in moving fr om evidence to \nACIP vaccine recommendations \nProvides transparency around the impact of additional fa ctors on \ndeliberations when considering a recommendation \nEtR question \nDoes ACIP recommend vaccination with the 2-dose* JYN NEOS vaccine series \nfor persons aged 18 years and older at risk †for mpox?\n*Dose 2 administered 28 days after dose 1 \n†Persons at risk: \n•Gay, bisexual, and other men who have sex with men,  transgender or nonbinary people who in the past \n6 months have had one of the following: \n•A new diagnosis of ≥ 1 sexually transmitted disease  \n•More than one sex partner \n•Sex at a commercial sex venue \n•Sex in association with a large public event in a g eographic area where mpox transmission is \noccurring \n•Sexual partners of persons with the risks described in above \n•Persons who anticipate experiencing any of the above\nPolicy question: Should the 2 dose JYNNEOS vaccine s eries* be recommended \nfor persons aged 18 years and older at risk †for mpox ?\nPopulation Persons aged 18 years and older at risk for mpox \nIntervention Vaccination with JYNNEOS® \nComparison No vaccination \nOutcome a) Prevention of disease \nb) Severity of disease \nc) Serious adverse events d) Myo-/ peri- carditis \n*Dose 2 administered 28 days after dose 1 \n†Persons at risk: \n• Gay, bisexual, and other men who have sex with men,  transgender or nonbinary people who in the past 6 months have had one of the following: \n• A new diagnosis of ≥ 1 sexually transmitted disease  \n• More than one sex partner \n• Sex at a commercial sex venue \n• Sex in association with a large public event in a g eographic area where mpox transmission is occurring \n• Sexual partners of persons with the risks described in above \n• Persons who anticipate experiencing any of the above\nEtR Domains \nEtR Domain Question(s) Public Health Problem •Is the problem of public health importance? \nBenefits and Harms •How substantial are the desirable anticipated effec ts? \n•How substantial are the undesirable anticipated eff ects? \n•Do the desirable effects outweigh the undesirable e ffects? \nValues •Does the target population feel the desirable effec ts are large relative to the undesirable \neffects? \n•Is there important variability in how patients valu e the outcome? \nAcceptability •Is the intervention acceptable to key stakeholders?\nEquity •What would be the impact of the intervention on hea lth equity? \nFeasibility •Is the intervention feasible to implement? \nResource Use •Is the intervention a reasonable and efficient allo cation of resources? \nPublic Health Problem \nAre continued mpox cases of public health importance? \n>1.25 million doses of JYNNEOS have been administered in t he United States \nHowever, national vaccine coverage remains lower than ide al, possibly \nbecause of lower perceived risk in the last 6 months \nMpox cases continue to occur domestically and internation ally, including in \nclusters \nModeling data suggests larger outbreaks may occur if va ccine coverage \nremains <50% nationally for persons at risk of mpox \nSevere disease and deaths continue to occur \n\nBenefits and Harms \nMain source of VE data has been three U.S. studies \nCDC EPIC study \nCDC Multi-jurisdictional study \nNew York State study \nEstimated VE for preventing mpox disease has ranged from 66-89% for the 2-dose vaccine series \nMulti-jurisdictional study:  estimate of VE for preventing infections among immunocompetent vs. self-reported immunocompromised persons \n*Adjusted for age, race/ethnicity, immunocompromise d status, reported close contact with a \nconfirmed/suspected mpox case in 3 weeks prior to i ndex event \n•Only recently able to evaluate VE of self-reported immunocompromised, confidence interval is still wid e \n•Modifications in protocol needed to evaluate VE for  objectively confirmed immunocompromised persons \nHow substantial are desirable anticipated effects o f \nJYNNEOS? \nACIP previously recommended use of JYNNEOS \n–Persons at increased risk of occupational exposure to orthopoxviruses \n–Persons at-risk for mpox during mpox outbreaks \nSubsequent data has supported its effectiveness for  the population \nimpacted by the ongoing outbreak \nHow substantial are desirable anticipated effects o f \nJYNNEOS? \nACIP previously recommended use of JYNNEOS \n–Persons at increased risk of occupational exposure to orthopoxviruses \n–Persons at-risk for mpox during mpox outbreaks \nNo new safety signals identified from pre-licensure  studies \nThe adverse events most commonly reported to VAERS have been \ninjection site symptoms (redness, swelling, pain, i tching) \n\nBalance between desirable effects relative to undesirable effects of JYNNEOS \nDesirable anticipated effects considered large \nUndesirable anticipated effects considered small Do the desirable effects outweigh the undesirable e ffects? \nFavors intervention        Favors comparison        Favors both         Favors neither         Unclear\n\nEtR Domain:  Values \nEarly in outbreak response: National surveys indica ted \nstrong interest in vaccine \nDuring Aug-Nov 2022, >85% of respondents in the Ame rican \nTransformative HIV Study (AMETHST) were interested in vaccine, and \nuptake doubled from August to September \nDuring August-Dec 2022, 50% of Porter-Novelli survey  responders who \nidentified as LGBTQ+ felt the vaccination is import ant to protect from mpox \nDuring Oct-Nov 2022, >70% of MSM in a San Francisco  survey of persons \nexperiencing homelessness reported that they would accept or have \naccepted vaccination \nDuring October-December 2022, an American Men’s Int erest Survey \n(AMIS) showed that those who were concerned about m pox were 3.5x \nmore likely to be vaccinated \nhttps://grants.nih.gov/grants/guide/rfa-files/RFA-A I-21-018.html \nhttps://emoryamis.org/wp-content/uploads/2022/08/20 22-Monkeypox-Survey.pdf \nhttps://www.cdc.gov/mmwr/volumes/71/wr/mm7135e1.htm\nFilardo TD. Vaccine. 2023 Sep 7;41(39):5673-5677. \nEarly in outbreak: Persons seeking vaccination were , \nas expected, supportive of the JYNNEOS vaccine \nDC PEP ++ Study: CDC and DC Health collaboration to follo w cohort of \npersons at elevated risk of mpox exposure in Washington D.C. who \npresented for JYNNEOS vaccination, Aug 2022-Oct 2022 \n–Survey with 866 adults \n–>85% agreed or strongly agreed that vaccines for mp ox should be available to \nanyone who wants the vaccine \n–82% were likely or very likely to get a third dose if it was recommended \nQualitative interviews August and September 2022 am ong adults \npresenting for JYNNEOS vaccine in Washington DC \n–Many participants grateful that LGBTQ+ were given p riority vaccine access \n(suggests interest in vaccine) \nHassan, R. (in press). Sexually Transmitted Diseases \nEarly in outbreak: Studies indicated conflicting fe elings \nabout receiving JYNNEOS vaccines \nCurtis et al. Survey with 320 persons, primarily MS M living in Illinois and at \nrisk for mpox. September 2022 \n–24.1% received 2 vaccine doses, 27.5% received one dose, 47.5% no doses \n–Persons who were vaccinated were more likely to hav e higher education, know \nsomeone with mpox, express concern about their safe ty, and less likely to \nreport recent food insecurity \nTurpin et al. Qualitative interviews with 24 Black MSM attending HIV \nprevention-related events in greater D.C. area, May  2022 \n–Lack of availability of mpox vaccines was common co ncern suggesting interest \n–Vaccine  hesitancy was also common \nhttps://pubmed.ncbi.nlm.nih.gov/37236817/ \nhttps://pubmed.ncbi.nlm.nih.gov/37510557/ \nMore recent:  State of vaccine confidence report, J une \n2023 \nReview of mpox-related discussions on 23 news and social media outlets in the Chicago area during the  \nmonth following the CDPH media release indicating a n \nincrease in mpox cases, particularly among previous ly \nvaccinated persons \nFindings: \n–Mpox vaccine hesitancy among general public and LGB TQ-\naffiliated groups noted \n–Questions raised \n•Effectiveness and safety of the vaccine (e.g., sent iment expressed \nthat vaccine is experimental) \n•Distrust in reporting (e.g., Suspicion that mpox re porting is \nexaggerated) \nhttps://www.cdc.gov/vaccines/covid-19/downloads/SoV C-MPOX-062723.pdf \nMore recent: Interviews with 18 patients associated  \nwith mpox cluster in Chicago, May 2023 \nFully vaccinated, partially vaccinated, unvaccinated intervie wed \nMost stated they would recommend vaccine to others \nMost vaccinated persons felt vaccine was effective in re ducing severity \nSome assumed it would prevent infection \nUnvaccinated reported initial interest in vaccine when supp ly was limited \nand they were unable to receive it; they reported they  did not seek it again \nbecause case counts decreased so they assumed diminish ed risk \nMore recent: Online focus group used by CDC to develop communication material, July 12, 2023 \nSession conducted with 52 persons \n–Participant inclusion criteria: \n•Identify as men (including transgender men and tran sgender women) \n•Unvaccinated for mpox and never diagnosed with mpox \n•18-45 years of age \n•Sex with 2 or more men within past 6 months \n–Participant demographics: average age 30-34 years; 48% Black, 37% White, 27% \nHispanic/Latino; 75% gay, 21% bisexual \nExposure to communication materials increased intere st in receiving mpox vaccine \n–Information about mpox vaccine safety, effectiveness , and current threat of mpox \naffected interest \n–Current risk of mpox and protecting community were m otivating \nSome people did not change their minds \nTarget population sentiments \nVaccine demand was high early in the outbreak response \nNational surveys with the affected population indicate ove rall interest in \nJYNNEOS vaccinations \n\nTarget population sentiments \nInterest and intent to get vaccinated varies among the  affected population \nLower perceived risk of mpox may contribute to reduced  interest in vaccine \nlater in the outbreak \n\nEtR Domain:  Acceptability \nStakeholder perceptions:  Health departments \nHealth departments requested JYNNEOS and organized va ccination \ncampaigns \nhttps://aspr.hhs.gov/SNS/Pages/JYNNEOS-Distribution .aspx \nStakeholder perceptions:  Sermo survey of clinicians\nSermo*: Online community of >1.3 million clinicians \nJuly 31 - August 1, 2022 survey results of U.S. clinicians (n=415): 69% felt U.S. without enough mpox vaccine to handle outbreak \nSeptember 12, 2022 survey of U.S. clinicians (n=62) \n•66% had treated at least one mpox patient \n•76% knew where a patient could get JYNNEOS vaccination \n•86% wanted to be able to provide vaccination in their office \n*https://app.sermo.com/barometer/unitedstates\nPorter-Novelli Survey of Pediatricians (n=102) and Family Practice (FP) Practitioners (n=104) \nAdded 3 mpox vaccine questions to survey on pediatri c COVID-19 vaccine \nattitudes and behaviors \nDescription of respondents' clinical practices: \n–85% of FP and 88% of Pediatricians cared for children 12-17 years \n–70% of FP and 60% of Pediatricians cared for patien ts 18+ years \n–Majority (75%) in private practice; 14% practiced i n FQHC \n–54% had >1500 patients in their practice \nPorter Novelli Survey: Preference to provide JYNNEOS  within medical practice, \nPN survey of Pediatricians (N=102) and Family Practitioners (n=104), August \n2023 \n\nShift in vaccine administration sites from public h ealth \nclinics to medical centers \n•Public health providers administered 40% of all vaccines through Mar 2023 \n•Medical care providers administered an increasing proportion of vaccines since the start of the outbreak \n•Pharmacies consistently provided 3-4% of all vaccines \nPublic Health \nProvider or \nClinic Medical \nCenter \nProvider Commercial \nVaccination \nService \nProvider Pharmacy Other Percentage of Doses Administered \nCategories of medical providers administering vacci nes \nFrom 2022 to 2023, there were statistically significant increases in vaccines provided by •Primary care offices \n•Federally qualifying health centers (FQHCs) \n•Other health centers \nPrimary \nCare Hospital FQHC Health \nCenter -\nOther Health \nCenter -\nSTD/HIV Percentage of Doses Administered \nFQHC: Federally qualifying health center \nOnline focus group by CDC: Healthcare provider perceptions of sexual health and mpox \nConducted to explore provider knowledge, attitudes,  and practices related to \nservice delivery, including those specific to mpox \nRecruitment targeting 50 providers via external rec ruiting firm \n41 total participants – diverse by gender, race/ethn icity, practice setting, payment \nmethods for patients (e.g., private insurance plans , Medicaid, Medicare, \ngovernment programs), and clinical profession \n61% reported spending ≥60% of their time providing sexual health services \n59% private healthcare setting, 29% private and pub licly funded, 10% publicly \nfunded \n54% in private practice, 20% STD/HIV/family plannin g clinic, 10% FQHC, 25% in ED \nor urgent care \nResponses from healthcare provider participants (N= 41) \n68% had never managed an mpox case \n34% believe mpox is a threat to public health \n32% reported mpox is important to their patient popu lations \n51% believe that mpox services (e.g., counseling) sh ould be integrated into \nstandard care for the following reasons \n–Increase access to vaccine \n–Improve education and awareness for patients \n–Ensure STI screening is comprehensive \nIs the intervention acceptable to key stakeholders \nIs the intervention acceptable to key stakeholders \nNo            Probably no           Uncertain           Probably yes           Yes Varies \nHealth departments and clinicians are supportive of mpox v accines even if \npediatricians would prefer to refer patients to other clin ics to receive \nJYNNEOS \nFamily practitioners would like to be able to provide JYNNEO S in their own \nclinics \nThere has been a shift from JYNNEOS provided by public health providers to \nJYNNEOS provided by medical center providers, including ST I and HIV clinics \nEtR Domain:  Resource Use \nIs the intervention a reasonable and efficient allocation of resources \nCurrent resources \n–Vaccine only available via national government stoc kpiles \n–JYNNEOS stockpiled for smallpox preparedness \n–Doses used need to be replenished \n–Significant use of resources (e.g., shipments, tran sportation, personnel) during \nthe outbreak and routine recommendation could be fu rther drain \nPotential resources in the future:  Uncertain wheth er it will be \ncommercialized but if so, unknown costs associated with commercialization \n\nEtR Domain:  Equity \nMpox and health equity \nDisproportionate impact of mpox \n–Gay, bisexual, and other MSM \n–Black and Hispanic persons \n–Persons experiencing homelessness \nAny vaccine administered may decrease the disparity betw een the affected \npopulation and others \nImpact on health equity \nWill facilitate 1:1 counseling and information shar ing in the privacy of a \nclinic; vaccine recommendation from a clinician is associated with \nincreased vaccine uptake \n$5,000,000 allocated to community-based organizations (C BOs) in \nSeptember 2023 to advance mpox prevention and vaccinat ion efforts* \n–CBOS essential to increasing vaccination coverage a mong those at highest risk \nand provided pivotal role during 2022 \n–42 CBOs funded so far \nIf commercialized, there may be an impact on primar y sites of vaccination \nand on health departments \nRecommendation might facilitate broad acceptance of  vaccination (e.g., by \ninsurance companies, patients) because endorsed by ACIP after rigorous review \n*https://www.cdcfoundation.org/pr/2023/mpox-vaccina tion-CBO-outreach \nWhat would be the impact on health equity \nWhat would be the impact on health equity? \nReduced                  Probably Reduced                Probably no impact            Probably increa sed \nIncreased                 Varies                                    Don’t know \nAccess to vaccine (vs. no vaccine) may improve the health of persons who \nare at risk for mpox \nRoutine recommendation may facilitate vaccinations \nEtR Domain:  Feasibility \nAccess to JYNNEOS vaccination if ACIP recommends it\nContinue via national stockpiles free of cost to patients and providers \nMpox provider agreements* do not have a termination da te; they will \ncontinue as long as vaccine is acquired via the US govern ment program and \ncan include new providers \nFunding † provided to CBOs may improve feasibility \nIf commercialized §\n–Via Medicare, Medicaid, commercial plans without copay \n–Uninsured children via Vaccines for Children Program \n–Some uninsured and underinsured adults might have difficu lty \n*https://www.cdc.gov/poxvirus/mpox/clinicians/provi der-agreement.html \n† https://www.cdcfoundation.org/pr/2023/mpox-vaccinat ion-CBO-outreach \n§Uncertain whether it will be commercialized \nIs the intervention feasible to implement? \nIs the intervention feasible to implement \nNo            Probably no           Uncertain           Probably yes           Yes Varies   \nSubcutaneous vaccine; easy to administer \nStanding orders available; JYNNEOS can be stored ref rigerated for 8 weeks \nRecent analysis of shift in vaccine providers demon strates the continued \nsuccessful integration of JYNNEOS into providers’ pra ctices (e.g., STI and HIV care \nsettings, HIV care pharmacies, LGBTQ+ affirming pri mary care practices) \nSTI, HIV, and most family medicine/internal medicin e providers comfortable \nproviding vaccines but some pediatricians may prefe r referring patient to other \nclinics \nIf commercialized, similar to other vaccines, cost of vaccine might impact access to \nsome populations \nSummary of EtR \nDomains Domains Domains \nBenefits:  How substantial are the desired anticipated effects Large Values:  Does the target population feel desirable effects are large Probably Yes Impact on health equity Probably increased \nHarms:  How substantial are undesirable anticipated effects? Small Is there important uncertainty about or variability in values? Possibly important uncertainty or variability Feasible to implement ? Probably Yes \nBenefit / Harm:  Favors intervention Acceptable to stakeholders? Yes Balance of consequences: \nReasonable and efficient allocation of resources? Uncertain \nBalance of Consequences \nUndesirable                                        Undesirable                                   Balan ce between \nconsequences clearly                       conseque nces probably               desirable and undesirab le \noutweigh desirable                           outwei gh desirable                       consequences is closely \nconsequences in most                      consequen ces in most                 balanced or uncertain \nsettings settings Desirable consequences                   Desirable consequences             There is insufficient evid ence \nprobably outweigh                             clear ly outweigh to determine the balance of \nundesirable consequences               undesirable consequences consequences \nin most settings                                  i n most settings X\nProposed recommendation \nACIP recommends vaccination* with the 2-dose †JYNNEOS vaccine series for \npersons aged 18 years and older at risk for mpox §?\n*Interim recommendation that ACIP will revisit in 2 -3 years \n† Dose 2 administered 28 days after dose 1 \n§Persons at risk: \n•Gay, bisexual, and other men who have sex with men,  transgender or nonbinary people who in the past \n6 months have had one of the following: \n•A new diagnosis of ≥ 1 sexually transmitted disease  \n•More than one sex partner \n•Sex at a commercial sex venue \n•Sex in association with a large public event in a g eographic area where mpox transmission is \noccurring \n•Sexual partners of persons with the risks described  in above \n•Persons who anticipate experiencing any of the abov e \nFor more information, contact CDC 1-800-CDC-INFO (232-4636) TTY:  1-888-232-6348    www.cdc.gov The findings and conclusions in this report are tho se of the authors and do not necessarily represent the \nofficial position of the Centers for Disease Contro l and Prevention. \nNational Center for Emerging and Zoonotic Infectiou s Diseases \nDivision of High-Consequence Pathogens and Patholog y Questions?", "summary": "National Center for Emerging and Zoonotic Infectiou s Diseases  Evidence to Recommendations Framework:  Vaccination with JYNNEOS for Persons At Risk of Mpo x  Advisory Committee on Immunization Practices October 25, 2023 Agam Rao, MD CAPT, US Public Health Service Poxvirus and Rabies Branch Centers for Disease Control and Prevention  Evidence to Recommendations (EtR) Framework  Structure to describe information considered in moving fr om evidence to  ACIP vaccine recommendations  Provides…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-25-26-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-10-25-26/03-MPOX-Rao-508.pdf", "doc_date": "2023-10-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 45}
{"title": "04 MPOX Rao 508", "content": "National Center for Emerging and Zoonotic Infectiou s Diseases \nClinical guidance and next steps \nAdvisory Committee on Immunization Practices October 25, 2023 Agam Rao, MD CAPT, US Public Health Service Poxvirus and Rabies Branch Centers for Disease Control and Prevention \nGuidance about vaccination before exposures to mpox\nSimilar to what has previously been presented to ACIP \nSpecific to pre-exposure vaccination \nSpecific to the population at risk for mpox* \n*Interim recommendation to be revisited in 2-3 year s \n† Dose 2 administered 28 days after dose 1 \n§Persons at risk: \n•Gay, bisexual, and other men who have sex with men,  transgender or nonbinary people who \nin the past 6 months have had one of the following:\n•A new diagnosis of ≥ 1 sexually transmitted disease  \n•More than one sex partner \n•Sex at a commercial sex venue \n•Sex in association with a large public event in a g eographic area where mpox \ntransmission is occurring \n•Sexual partners of persons with the risks described  in above \n•Persons who anticipate experiencing any of the abov e \nPersons <18 years of age at risk for mpox \nJYNNEOS is not licensed for persons <18 years of age \nNo pre-licensure studies in this population; however, no safety signals identified during the current outbreak \nNIH clinical trial in progress:  Safety and immunogenicity of JYNNEOS in persons aged 12-17 years \nAdolescents at risk for mpox* may receive the JYNNEOS vaccine before an exposure \n*See slide 2 for description of population at risk for mpox \nPregnant or breastfeeding persons \nPregnancy \n–Available human data insufficient to determine vacc ine associated risks \n–However, animal models including in rats have shown  no evidence of harm to \nthe developing fetus \n–No adverse events reported via vaccine safety surve illance systems \nSafety in breastfeeding persons \n–Has not been evaluated \n–No adverse events reported via vaccine safety surve illance systems \nJYNNEOS is not contraindicated in pregnancy or whil e breastfeeding \nPregnant or breastfeeding persons at risk for mpox*  may receive the JYNNEOS \nvaccine before an exposure \n*See slide 2 for description of population at risk for mpox \nHealthcare personnel \nHealthcare-associated mpox infections have been rare , typically \nassociated with sharps injuries or exposure in the absence of personal \nprotective equipment \nHealthcare personnel at risk for mpox because of the  risk factors \ndescribed (e.g., MSM with more than one sexual part ner) should be \nvaccinated; however, this recommendation is not bec ause of \noccupational risk \nJYNNEOS is not recommended as a routine vaccination  for healthcare \npersonnel unless sexual risk factors are present \n\nMyopericarditis \nKnown risk after ACAM2000, a different orthopoxviru s vaccine; mechanism \nunknown so theoretical risk with JYNNEOS has not be en ruled out \nKnown risk after COVID-19 vaccines, particularly in  adolescent and young adult \nmales \nCDC websites for COVID-19 and mpox vaccines provide interim guidance for \ncoadministration \nCDC guidance for coadministration of JYNNEOS with COVID-19 vaccines \nThere is no required minimum interval between recei ving any COVID-19 \nvaccine and JYNNEOS vaccine (e.g., for mpox prevent ion), regardless of \nwhich vaccine is administered first \nPeople, particularly adolescent and young adult mal es, who are \nrecommended to receive both vaccines might consider  waiting 4 weeks \nbetween vaccines. This is because of the observed r isk for myocarditis and \npericarditis after receipt of ACAM2000 orthopoxviru s vaccine and COVID-\n19 vaccines and the hypothetical risk for myocardit is and pericarditis after \nJYNNEOS vaccine. However, if a patient’s risk for mp ox or severe disease \ndue to COVID-19 is increased, administration of JYN NEOS and COVID-19 \nvaccines should not be delayed \nhttps://www.cdc.gov/vaccines/covid-19/clinical-cons iderations/interim-considerations-us.html \nClinical guidance when JYNNEOS and immunoglobulin products are temporally administered \nMost immunoglobulin products: No precautions are necessa ry if JYNNEOS \nis administered in close temporal proximity to Intravenous immunoglobulin \n(IVIG) \nVaccinia immune globulin intravenous (VIGIV) \n–Could interfere with immune response to JYNNEOS \n•Ideally, administration of JYNNEOS should be delayed  if VIGIV was recently administered \n•The duration for which it should be delayed is unkn own; public health consultation \nshould be obtained for case specific guidance \n–Unlikely that VIGIV would be administered in close proximity to JYNNEOS \nContraindications and precautions \nJYNNEOS was licensed* for prevention of smallpox in addition to \nprevention of mpox \nBecause smallpox is nearly always life-threatening, there are no absolute \ncontraindications; however, for mpox, considerations  may be different \nConsistent with contraindications in ACIP routine s chedules, WG proposed \n–JYNNEOS contraindicated in patients with a severe a llergic reaction (e.g., \nanaphylaxis) after a previous dose or to a vaccine component \n–Precautions: Moderate or severe acute illness, with or without fever \n*https://www.fda.gov/media/131078/download \nOther administration guidance \nCompletion of the 2-dose series should be encouraged \nAs much as possible, the 2 nd dose of JYNNEOS should be administered ~28 \ndays after the first dose \nUnintentional delays in receiving the 2 nd dose does not require restarting \nthe series; the second dose should be administered as s oon as possible \neven if >1 year has elapsed \nNext steps \nTentative timeline for ACIP discussions and votes* \nInterim routine recommendation and clinical guidance \nOctober 2023 Early 2024 Possibly 2024 Publication of 2 MMWRs: 1) Use of JYNNEOS during mpox \noutbreaks \n2) Use of JYNNEOS among \npersons at risk during the ongoing mpox outbreak Consider results from NIH trial about use of JYNNEOS in persons aged 12-18 years \n*February 2023 and June 2023 votes do not impact ex isting recommendations for the current mpox outbrea k. \nJuniYYT7https://www.cdc.gov/poxvirus/monkeypox/interim-cons iderations/overview.html ~2025/2026 Review epidemiology, cost-effectiveness analysis, and other data to determine if routine recommendation should be continued \nProposed recommendation is interim recommendation \nIf passed, recommendations will be revisited in 2-3 years \nEpidemiology at the time may inform decision about continuin g routine \nvaccinations \nVaccine may be commercialized by that time \nCost-effectiveness analysis will be performed \nAcknowledgements \nACIP Work Group \nHoward Minkoff \nJane Zucker \nJim Campbell \nSathesh Panayampalli \nAlli Tuttle \nJonathan Duffy \nRosalind Carter \nNeil Murthy \nPatricia Wodi Mark Russi \nMarie de Perio \nJason Zucker \nJohn Brooks \nDavid Kuhar \nEvelyn Twentyman \nSara Oliver \nFor more information, contact CDC 1-800-CDC-INFO (232-4636) TTY:  1-888-232-6348    www.cdc.gov The findings and conclusions in this report are tho se of the authors and do not necessarily represent the \nofficial position of the Centers for Disease Contro l and Prevention. \nNational Center for Emerging and Zoonotic Infectiou s Diseases \nDivision of High-Consequence Pathogens and Patholog y Questions?", "summary": "National Center for Emerging and Zoonotic Infectiou s Diseases  Clinical guidance and next steps  Advisory Committee on Immunization Practices October 25, 2023 Agam Rao, MD CAPT, US Public Health Service Poxvirus and Rabies Branch Centers for Disease Control and Prevention  Guidance about vaccination before exposures to mpox Similar to what has previously been presented to ACIP  Specific to pre-exposure vaccination  Specific to the population at risk for mpox*  *Interim recommendation to be…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-25-26-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-10-25-26/04-MPOX-Rao-508.pdf", "doc_date": "2023-10-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 15}
{"title": "01 Kotton Adult RSV 508", "content": "Centers for Disease Control and Prevention \nNational Center for Immunization and Respiratory Di seases \nPhotographs and images included in this presentation a re licensed solely for CDC/NCIRD online and present ation \nuse. No rights are implied or extended for use in pr inting or any use by other CDC CIOs or any external audiences. \nAdult Respiratory Syncytial Virus (RSV) Session \nCamille Kotton, MD Chair, Adult RSV Work Group \nAdvisory Committee on Immunization Practices (ACIP)October 25, 2023 \nRSVPreF3 (Arexvy, GSK) is a 1-dose adjuvanted (AS01 E) \nrecombinant prefusion F protein (preF) vaccine. \nRSVpreF (Abrysvo, Pfizer) is a 1-dose recombinant preF vacci ne. In June 2023, CDC’s Advisory Committee on Immunizat ion \nPractices (ACIP) voted to recommend that adults age s 60 \nyears and older may receive a single dose of RSV va ccine \nusing shared clinical decision making. \nhttps://www.cdc.gov/mmwr/volumes/72/wr/mm7229a4.htm2\nThe Work Group reviewed CDC vaccine safety surveill ance plans for RSV vaccination in \nadults ≥60 years. \nGSK shared with the Work Group results of an immuno -bridging study showing non-\ninferior humoral immune responses to RSV vaccinatio n in immunocompetent adults \n50–59, compared with immunocompetent adults ≥60 (in  whom efficacy was \ndemonstrated). \nThe Work Group discussed the potential role of RSV vaccination in adults younger than \n60 years, including subpopulations that would benef it most from vaccination and \nequity implications. Issues under discussion since the June meeting \n3\nThe Work Group reviewed CDC vaccine safety surveillan ce plans for RSV \nvaccination in adults ≥60 years. \n–V-safe ( https://vsafe.cdc.gov ) has launched for older adult RSV vaccination \n–Today’s session will not include RSV vaccine uptake  data or safety surveillance data; \ndata are premature this early into the vaccination program \n–Uptake and safety results will be shared at a futur e ACIP meeting Issues under discussion since the June meeting \n4\nAgenda: Wednesday October 25, 2023 \nRSVPreF3 safety and immunogenicity in adults aged 50–59 years, compared with adults aged ≥60 years \nEpidemiology of RSV hospitalization in adults, with  a \nfocus on adults aged 50–59 years \nWork Group considerations regarding RSV vaccination in adults aged 50–59 years Dr. Susan Gerber (GSK) Dr. Monica Patton (CDC) Dr. Amadea Britton (CDC) \n5\nAdult RSV Work Group Membership \n6ACIP Voting Members \nCamille Kotton (Chair) Keipp Talbot Sarah Long Ex Officio Members \nRachel Zhang (FDA) Judy Beeler (FDA) Nicholas Geagan (FDA) Nadine Peart Akindele (FDA) Sonnie Kim (NIH/NIAID) Jeffrey Kelman (CMS) Michelle Juaneza (HRSA/VICP)Uzo Chukwuma (IHS) Valerie Marshal (OIDP) Consultants \nRobert Atmar (Baylor Coll. of Medicine) Helen Chu (U Washington) Peter Donofrio (Vanderbilt University) Marie Griffin (Vanderbilt University) Cynthia Lucero-Obusan (VHA) Tracy Ruckwardt (NIH/NIAID) Jonathan Temte (U Wisconsin) Rebecca Morgan (Case Western) Doug Campos-Outcalt (U Arizona) \nLiaisons \nKenneth Schmader (AGS) Vidya Sundareshan (ACP) Gretchen LaSalle (AAFP) April Killikelly (NACI/PHAC) Winnie Su (NACI/PHAC) Katherine Williams (APTR) Ruth Lynfield (NFID) Bindy Crouch (AIM) Steven Pergam (IDSA) Elizabeth Skoy (APhA)\nCDC Contributors \nAmadea Britton (co-lead) Michael Melgar (co-lead) Lauren Roper Fiona Havers Chris Taylor Monica Patton Meredith McMorrow Diya Surie Jennifer DeCuir Mila Prill Monica Godfrey Ruth Link-Gelles Amanda Payne Danielle Moulia Megan Wallace Natalie Thornburg Melissa Coughlin Jefferson Jones Katherine Fleming-Dutra Ismael Ortega Sanchez Noelle Molinari Pragna Patel Aron Hall Hannah Rosenblum Derrell Powers Raigan Wheeler Jarrett Gartin Elizabeth Greene Manisha Patel Lisa Grohskopf Anne Hause David Shay Christine Olson Tom Shimabukuro Karen Broder Neil Murthy Patricia Wodi Andrew Leidner Jamison Pike Sarah Meyer Nicole Dowling \n7\nFor more information, contact CDC 1-800-CDC-INFO (232-4636) TTY:  1-888-232-6348    www.cdc.gov \nThe findings and conclusions in this report are tho se of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Pre vention. \nPhotographs and images included in this presentatio n are licensed solely for CDC/NCIRD online and pres entation \nuse. No rights are implied or extended for use in p rinting or any use by other CDC CIOs or any externa l audiences.", "summary": "Centers for Disease Control and Prevention  National Center for Immunization and Respiratory Di seases  Photographs and images included in this presentation a re licensed solely for CDC/NCIRD online and present ation  use. No rights are implied or extended for use in pr inting or any use by other CDC CIOs or any external audiences.  Adult Respiratory Syncytial Virus (RSV) Session  Camille Kotton, MD Chair, Adult RSV Work Group  Advisory Committee on Immunization Practices (ACIP)October 25,…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-25-26-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-10-25-26/01-Kotton-Adult-RSV-508.pdf", "doc_date": "2023-10-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 8}
{"title": "02 gerber adult RSV 508", "content": "CO-1\nACIP October 25, 2023\nSusan Gerber, MD\nMedical Director \nPresentation by GSK at ACIP Oct 25, 2023\n\nCO-2\nSubstantial RSV Disease Burden and Unmet Medical Need in US \nAdults Aged 50 –59 Years \nRSV-associated hospitalizations and medically -attended RSV illnesses are \nsubstantial among 50 -59 YOA\nPublished incidence rates likely substantially underestimate RSV burden due to lack \nof awareness, standardized testing, and underdetection within surveillance studies\nComorbidities associated with severe RSV disease are prevalent among adults 50–59 YOA\nPresentation by GSK at ACIP Oct 25, 20231\n2\n3\nObserved disparities by race and ethnicity are particularly pronounced with respectto hospitalization rates among middle aged adults 50 –64 YOA4\nYOA, years of age\nCO-3\nDisparities by Race and Ethnicity in RSV Hospitalization Rates  \nParticularly Pronounced in Adults 50 –64 Years\nHispanic:  1.0-1.9 times higher \nAI/AN, non -Hispanic: 1.6-2.1 times higher \nBlack, non -Hispanic: 1.8-2.7 times higherAmong adults aged 50–64 YOA , \nunadjusted RSV -related hospitalization rates \n(vs White, non- Hispanic) during 2018–2023 were:\nGraphs independently created for GSK from original data; A/PI, Asian and Pacific Islander, AI/AN, America Indian or Alaska Native; \n1. CDC, https://www.cdc.gov/rsv/research/rsv -net/dashboard.html . (accessed October 2023)A/PI, non -Hispanic White, non -Hispanic Hispanic AI/AN, non -Hispanic Black, non- Hispanic\nPresentation by GSK at ACIP Oct 25, 2023Unadjusted RSV -related hospitalization incidence per 100,000 \nby race / ethnicity and season from RSV -NET data1\nRSV \nHospitalization \nIncidence per \n100,000\n010203040\n2018-2019 2019-2020 2020-2021 2021-2022 2022-202350–64 years\nCO-4\nImmune Response and Safety Among Adults \n50–59 Years of Age (RSV-OA=ADJ-018): \nDay 31 Analysis\nPhase 3, observer -blind, randomized, placebo-controlled study to evaluate  \nnon-inferiority of the immune response and safety of RSVPreF3 + AS01E\nvaccine in adults 50– 59 years of age, including adults at increased risk of RSV \nlower respiratory tract disease, compared with adults 60 years of age and older\nPresentation by GSK at ACIP Oct 25, 2023\nCO-5\nPrimary Objective\nClinicalTrials.gov. NCT05590403. https://www.clinicaltrials.gov/study/NCT05590403 ; (accessed September 2023) \n1. RSV OA=ADJ -018 study protocol RSV-OA=ADJ -018 \nPresentation by GSK at ACIP Oct 25, 2023Primary objective: To demonstrate the non-inferiority of the humoral immune response in participants \n50–59YOA with and without comorbidities well -documented to be related to RSV -associated severe disease \ncompared with older adults (≥ 60 YOA) after RSVPreF3 + AS01E vaccine administration\nCO-6\nPrimary Endpoints\nPresentation by GSK at ACIP Oct 25, 2023CI, confidence interval; SRR: SeroResponse Rate ( % of participants with ≥4- fold increase from pre- vaccination serum antibody titers); \nGMT, geometric mean titer;ClinicalTrials.gov. NCT05590403. https://www.clinicaltrials.gov/study/NCT05590403 ; \n(accessed September 2023) 1. RSV OA=ADJ -018 study protocol \nPrimary Endpoints\nRSV-A neutralization titers at 1 month \nafter RSVPreF3 + AS01E administration\nRSV-B neutralization titers at 1 month \nafter RSVPreF3 + AS01E administration\nSuccess criteria1:Upper limit of 2-sided \n95% CI for GMT ratio is ≤ 1.5 and SRR \ndifference is ≤10%RSV-OA=ADJ -018 \nStudy populations:\n50–59 YOA with comorbidities associated with RSV -LRTD vs ≥ 60 YOA \n50–59 YOA without  comorbidities associated with RSV -LRTD vs ≥ 60 YOA  Primary objective: To demonstrate the non-inferiority of the humoral immune response in participants \n50–59YOA with and without comorbidities well -documented to be related to RSV -associated severe disease \ncompared with older adults (≥ 60 YOA) after RSVPreF3 + AS01E vaccine administration\nCO-7\nImmunogenicity Endpoints\nPresentation by GSK at ACIP Oct 25, 2023ClinicalTrials.gov. NCT05590403. https://www.clinicaltrials.gov/study/NCT05590403 ; (accessed September 2023)\n1. RSV OA=ADJ -018 study protocol \n50-59RSV-OA=ADJ -018 \nPrimary Endpoints\nRSV-A neutralization titers at 1 month \nafter RSVPreF3 + AS01E administration\nRSV-B neutralization titers at 1 month \nafter RSVPreF3 + AS01E administration\nSuccess criteria1:Upper limit of 2-sided \n95% CI for GMT ratio is ≤ 1.5 and SRR \ndifference is ≤10%Immunogenicity Endpoints\nRSV-A / RSV-B GMT pre vaccination and \nat 1, 6, and 12 months after vaccination\nTertiary endpoint: analysis by \nbaseline comorbidities\nFrequency of RSVPreF3 + AS01E\nspecific CD4+ T cells expressing at least 2 activation markers at pre -vaccination \nand at 1, 6, and 12 months after vaccinationPrimary objective: To demonstrate the non-inferiority of the humoral immune response in participants \n50–59YOA with and without comorbidities well -documented to be related to RSV -associated severe disease \ncompared with older adults (≥ 60 YOA) after RSVPreF3 + AS01E vaccine administration\nStudy populations:\n50–59 YOA with comorbidities associated with RSV -LRTD vs ≥ 60 YOA \n50–59 YOA without  comorbidities associated with RSV -LRTD vs ≥ 60 YOA  \nCO-8\nSafety Endpoints\nAE, adverse events; SAE; serious adverse events; pIMD , potential immune mediated disease\nClinicalTrials.gov. NCT05590403. https://www.clinicaltrials.gov/study/NCT05590403 ; (accessed September 2023)\n1. RSV OA=ADJ -018 study protocol Presentation by GSK at ACIP Oct 25, 2023\n50-59Safety Endpoints\nSolicited administration site / systemic \nevent with onset within 4 days\nUnsolicited AEs within 30 days \nSAEs and pIMDs up to Month 6\nRelated SAEs, fatal SAEs and related pIMDs up to study end (Month 12)Immunogenicity Endpoints\nRSV-A / RSV-B GMT pre vaccination and \nat 1, 6, and 12 months after vaccination\nTertiary endpoint: analysis by baseline comorbidities\nFrequency of RSVPreF3 + AS01\nE\nspecific CD4+ T cells expressing at least 2 activation markers at pre -vaccination \nand at 1, 6, and 12 months after vaccinationRSV-OA=ADJ -018 \nPrimary Endpoints\nRSV-A neutralization titers at 1 month \nafter RSVPreF3 + AS01E administration\nRSV-B neutralization titers at 1 month \nafter RSVPreF3 + AS01E administration\nSuccess criteria1:Upper limit of 2-sided \n95% CI for GMT ratio is ≤ 1.5 and SRR \ndifference is ≤10%Primary objective: To demonstrate the non-inferiority of the humoral immune response in participants \n50–59YOA with and without comorbidities well -documented to be related to RSV -associated severe disease \ncompared with older adults (≥ 60 YOA) after RSVPreF3 + AS01E vaccine administration\nStudy populations:\n50–59 YOA with comorbidities associated with RSV -LRTD vs ≥ 60 YOA \n50–59 YOA without  comorbidities associated with RSV -LRTD vs ≥ 60 YOA  \nCO-9\nRSVPreF3 + AS01E\nn=382Study Design\nRandomized, placebo- controlled, observer -blind, multi -country study\nYOA, years of age; LRTD, lower respiratory tract disease; w/o, without; ClinicalTrials.gov. NCT05590403. \nhttps://www.clinicaltrials.gov/study/NCT05590403 ; (accessed September 2023) 1. RSV OA=ADJ- 018 study protocol Randomization (2:1)\nRSVPreF3 + AS01ECurrent analysis Study initiation:\nOctober 2022\nBlood sampleVisit 1\nDay 1Visit 2\nDay 31Visit 3\nMonth 6Visit 4\nMonth 12\nCohort 1: \nAdults 50– 59 YOA, n=1140\nCohort 1b\nn=570 RRSVPreF3 + AS01E\nn=383\nPlacebo group\nn=192Cohort 1a\nn=570RRSVPreF3 + AS01E\nn=386\nPlacebo \nn=191\nMonth 6 analysis\nPlaceboCohort 2: \n≥ 60 YOA, n=380\nSafety monitoringCohort 1b: \nAdults w/o comorbidities associated with RSV -LRTD\nParticipants with chronic stable medical conditions with or without specific treatment, such as hypertension, hypercholesterolemia, or hypothyroidism, and not at increased risk for RSV -LRTD Cohort 1a: Adults with comorbidities associated with RSV -LRTD\nParticipants with ≥ 1 of following medical conditions:\nChronic pulmonary disease resulting in activity restricting symptoms or use of long -term medication\nChronic cardiovascular disease\nDiabetes mellitus types 1 and 2\nChronic kidney disease\nChronic liver disease \nCohort 2: ≥ 60 YOA cohortParticipants with chronic stable medical conditions\nPresentation by GSK at ACIP Oct 25, 2023Inclusion Criteria1RSV-OA=ADJ -018 \nCO-10\n8 Countries with Enrolled Participants \nN=1,534 (Exposed Set)\nCanada\nN=220\nArgentina\nN=178\nNetherlands \nN=39\nJapan\nN=150\nPoland \nN=144\nSpain \nN=198\nUnited States\nN=357\nGermany \nN=248\nPresentation by GSK at ACIP Oct 25, 2023RSV-OA=ADJ -018 \nCO-11\nDemographic Characteristics Well -Balanced\nExposed Set50 –59 YOA\nCohort 1a: Adults with comorbidities associated \nwith RSV -LRTD50 –59 YOA \nCohort 1b: Adults without  comorbidities \nassociated with RSV -LRTD ≥ 60 YOA\nCharacteristicRSVPreF3 + AS01E\n(N=386)Placebo\n(N=191)RSVPreF3 + AS01E\n(N=383)Placebo\n(N=192)RSVPreF3 + AS01E\n(N=382)Total\n(N=1534)\nMean age, years (SD) 55.3 (2.8) 55.6 (2.8) 54.8 (2.8) 54.7 (2.8) 69.5 (6.9) 58.6 (7.5)\nAge category, n (%)\n50–59 YOA 386 (100) 191 (100) 383 (100) 192 (100) 0 1152 (75.1)\n60–69 YOA 0 0 0 0 203 (53.1) 203 (13.2)\n70–79 YOA 0 0 0 0 130 (34.0) 130 (8.5)\n≥ 80 YOA 0 0 0 0 49 (12.8) 49 (3.2)\nFemale, n (%) 186 (48.2) 85 (44.5) 221 (57.7) 119 (62.0) 188 (49.2) 799 (52.1)\nBody Mass Index (BMI) kg/m2, mean (SD) 30.9 (6.8) 31.3 (7.3) 28.4 (5.9) 28.4 (6.7) 28.1 (6.0) 29.3 (6.6)\nRace, n (%)\nAmerican Indian or Alaska Native 4 (1.0) 3 (1.6) 1 (0.3) 0 (0) 1 (0.3) 9 (0.6)\nAsian 42 (10.9) 23 (12.0) 41 (10.7) 22 (11.5) 44 (11.5) 172 (11.2)\nBlack or African American 15 (3.9) 3 (1.6) 14 (3.7) 8 (4.2) 11 (2.9) 51 (3.3)\nNative Hawaiian or Other Pacific Islander 0 (0) 2 (1.0) 0 (0) 0 (0) 1 (0.3) 3 (0.2)\nWhite 324 (83.9) 158 (82.7) 320 (83.6) 158 (82.3) 324 (84.8) 1284 (83.7)\nMultiple 1 (0.3) 1 (0.5) 4 (1.0) 3 (1.6) 0 (0) 9 (0.6)\nUnknown 0 (0) 1 (0.5) 3 (0.8) 1 (0.5) 1 (0.3) 6 (0.4)\nEthnicity, n (%)\nHispanic or Latino 63 (16.3) 35 (18.3) 48 (12.5) 23 (12.0) 50 (13.1) 219 (14.3)\nUnknown 0 (0) 0 (0) 0 (0) 1 (0.5) 1 (0.3) 2 (0.1)\nPresentation by GSK at ACIP Oct 25, 2023SD, standard deviation; *Participants with underlying medical conditions such as chronic pulmonary and cardiovascular diseases, \ndiabetes mellitus types 1 and 2, and chronic liver and renal diseasesRSV-OA=ADJ -018 \nCO-12\nClinical Characteristics Well -Balanced\nExposed Set50 –59 YOA\nCohort 1a: Adults with comorbidities associated \nwith RSV -LRTD50 –59 YOA \nCohort 1b: Adults without  comorbidities \nassociated with RSV -LRTD ≥ 60 YOA\nCharacteristicRSVPreF3 + AS01E\n(N=386)Placebo\n(N=191)RSVPreF3 + AS01E\n(N=383)Placebo\n(N=192)RSVPreF3 + AS01E\n(N=382)Total\n(N=1534)\nComorbidity of interest, n (%)\n1 pre- existing comorbidity of interest 269 (69.7) 140 (73.3) 0 (0) 0 (0) 93 (24.3) 502 (32.7)\n≥ 2 pre- existing comorbidities of interest 117 (30.3) 51 (26.7) 0 (0) 0 (0) 51 (13.4) 219 (14.3)\nChronic pulmonary disease 147 (38.1) 77 (40.3) 0 (0) 0 (0) 58 (15.2) 282 (18.4)\nChronic cardiovascular disease 124 (32.1) 58 (30.4) 0 (0) 0 (0) 56 (14.7) 238 (15.5)\nDiabetes mellitus 188 (48.7) 91 (47.6) 0 (0) 0 (0) 68 (17.8) 347 (22.6)\nChronic liver or renal disease 56 (14.5) 23 (21.0) 0 (0) 0 (0) 18 (4.7) 97 (6.3)\nSmoking status for tobacco, n (%)\nCurrent smoker 83 (21.5) 49 (25.7) 66 (17.2) 36 (18.8) 45 (11.8) 279 (18.2)\nFormer smoker 133 (34.5) 50 (26.2) 99 (25.8) 37 (19.3) 133 (34.8) 452 (29.5)\nNever smoker 170 (44.0) 92 (48.2) 217 (56.7) 119 (62.0) 204 (53.4) 802 (52.3)\nUnknown 0 (0) 0 (0) 1 (0.3) 0 (0) 0 (0) 1 (0.1)\nPresentation by GSK at ACIP Oct 25, 2023*Participants with underlying medical conditions such as chronic pulmonary and cardiovascular diseases, diabetes mellitus types \n1 and 2, and chronic liver and renal diseases\nComorbidities: Overall, most common comorbidity of interest was diabetes mellitus and \nleast common was chronic liver or renal diseaseRSV-OA=ADJ -018 \nCO-13\nImmunogenicity\nRSV-OA=ADJ -018: Day 31 Analysis (Preliminary) \nData Lock Point: July 26, 2023\nPresentation by GSK at ACIP Oct 25, 2023\nCO-14\nGMT Ratio \n(without comorbidities associated with RSV -LRTD)GMT Ratio\n(95% CI)\nRSV-A\nCohort 2 (≥ 60) divided by\nCohort 1b (50 –59)0.95\n(0.83, 1.09)\nRSV-B\nCohort 2 (≥ 60) divided by\nCohort 1b (50 –59)0.90\n(0.79, 1.03)\n0.5 1.0 1.5 2.0Co-Primary Endpoint Met: Humoral Response to RSV Vaccine\nDemonstrated Non- Inferiority in Adults 50 –59 YOA vs Adults ≥ 60 YOA\nDay 31, Per Protocol Set for Humoral\nSuccess Criteria: Upper limit of 2- sided CI for GMT ratio is ≤1.5\nPresentation by GSK at ACIP Oct 25, 2023Cohort 1a: Adults 50- 59 with comorbidities associated with RSV -LRTD ; Cohort 1b: Adults 50- 59 without comorbidities associated with RSV -LRTD ; Cohort 2: Adults ≥ 60 YOA\nGMT, geometric mean titer; CI, confidence interval; LRTD, lower respiratory tract disease; Preliminary data; RSV response evaluated using NAb (ED60); \nED60, serum estimated dilution inducing 60% inhibition in plaque- forming units; Nab, neutralizing antibodyGMT Ratio \n(with comorbidities associated with RSV -LRTD)GMT Ratio\n(95% CI)\nRSV-A\nCohort 2 (≥ 60) divided by\nCohort 1a (50 –59)0.84\n(0.73, 0.96)\nRSV-B\nCohort 2 (≥ 60) divided by\nCohort 1a (50 –59)0.82\n(0.72, 0.93)\n0.5 1.0 1.5 2.0\nCO-15\nSeroresponse Rate [SRR] \n(without comorbidities associated with RSV -LRTD)SRR Difference\n(95% CI)\nRSV-A\nCohort 2 (≥ 60) minus\nCohort 1b (50 –59)−2.54\n(−8.45, 3.40)\nRSV-B\nCohort 2 (≥ 60) minus\nCohort 1b (50 –59)−3.82\n(−10.27, 2.68)Co-Primary Endpoint Met: SRRs for RSV -A and RSV- B NAbs  \nDemonstrated Non- Inferiority in Adults 50 –59 YOA vs Adults ≥ 60 YOA\nDay 31, Per Protocol Set for Humoral\n-15.0 -10.0 -5.0 0.0 5.0 10.0 15.0\nPresentation by GSK at ACIP Oct 25, 2023Success Criteria: Upper limit of 2- sided CI for SRR difference is <10%RSV-OA=ADJ -018 \nSeroresponse Rate [SRR]\n(with comorbidities associated with RSV -LRTD)SRR Difference\n(95% CI)\nRSV-A\nCohort 2 (≥ 60)  minus\nCohort 1a (50 –59)−6.67\n(−12.26, −1.12)\nRSV-B\nCohort 2 (≥ 60) minus\nCohort 1a (50 –59)−7.60\n(−13.79, −1.40)\n-15.0 -10.0 -5.0 0.0 5.0 10.0 15.0\nCohort 1a: Adults 50- 59 with comorbidities associated with RSV -LRTD ; Cohort 1b: Adults 50- 59 without comorbidities associated with RSV -LRTD ; Cohort 2: \nAdults ≥ 60 YOA ; Preliminary data; RSV response evaluated using NAb (ED60); SRR, Seroresponse rate defined as % of participants with \n≥ 4-fold increase of post -vaccination titers vs pre -vaccination titers (post -vacc  titers/pre -vacc  titers ≥ 4)\nCO-16\n110100100010000100000PRE PI(D31)Cohort 1b: \n50–59 YOA\nwithout comorbiditiesFrequency of RSVPreF3 Specific CD4+ T -Cell Response \nConsistent for 50– 59 YOA Compared with ≥ 60 YOA\nPI(D31)\nIncrease in RSVPreF3 \nspecific CD4+ \nT-cells observed in all \ngroups that received \nRSVPreF3 + AS01E\nvaccine\n110100100010000100000PRE PI(D31)Cohort 1a:\n50–59 YOA \nwith comorbidities\n110100100010000100000PRECohort 2:\n≥ 60 YOA\nFrequency of \nRSVPreF3 \nSpecific \nCD4+T -cells \nPresentation by GSK at ACIP Oct 25, 2023Q1 and Q3 are 25th and 75th percentiles.  PRE, Pre -vaccination; PI(D31), 1 month post RSV vaccination; Q, quartile; \nFrequency of RSVPreF3 specific CD4+T -cells expressing ≥ 2 markers including ≥ 1 cytokine (CD40L, 4- 1BB, TNF -α, IFN -γ, IL-13, \nand IL -17  (per million of CD4+T -cells by intracellular cytokine staining ) - per protocol set for cell mediated immune responseMedianQ3\nQ1\nMinimumMaximumKey\nN = 55 N = 45 N = 46 N = 44 N = 24 N = 22\nCO-17\nSafety\nRSV-OA=ADJ -018: 6 Month Analysis\nSafety Lock Point: July 21, 2023\nPresentation by GSK at ACIP Oct 25, 2023\nCO-18\nSolicited Local and Systemic Adverse Events (AE)\nLow reporting (< 5%) of Grade 3 events across groups; \nMost common local AE: pain and systemic A Es: fatigue, headache, myalgia\nPercent of \nParticipants \n(95% CI)\n0.0\n0.01.1\n0.00.83.2\n0.53.7\n0.02.1\n0.0\n0.00.3\n0.00.01.6\n0.01.8\n1.6 1.13.4\n0.52.1\n1.11.8\n0.30.5 0.00.5 0.03.4\n1.01.8\n1.10.82.7\n0.02.4\n1.10.8\n11.9\n0.514.5\n0.512.176.4\n10.575.2\n13.861.1\n9.3\n1.011.6\n0.57.626.0\n5.820.8\n10.112.943.8\n17.335.9\n19.0 23.7\n3.7 1.0 2.61.1 1.635.8\n16.827.7\n16.9 21.139.0\n5.832.2\n13.821.1\n0255075100\nCohort 1b RSV\nCohort 1b Placebo\nCohort 1a* RSV\nCohort 1a* Placebo\nCohort 2\nCohort 1b RSV\nCohort 1b Placebo\nCohort 1a* RSV\nCohort 1a* Placebo\nCohort 2\nCohort 1b RSV\nCohort 1b Placebo\nCohort 1a* RSV\nCohort 1a* Placebo\nCohort 2\nCohort 1b RSV\nCohort 1b Placebo\nCohort 1a* RSV\nCohort 1a* Placebo\nCohort 2\nCohort 1b RSV\nCohort 1b Placebo\nCohort 1a* RSV\nCohort 1a* Placebo\nCohort 2\nCohort 1b RSV\nCohort 1b Placebo\nCohort 1a* RSV\nCohort 1a* Placebo\nCohort 2\nCohort 1b RSV\nCohort 1b Placebo\nCohort 1a* RSV\nCohort 1a* Placebo\nCohort 2\nCohort 1b RSV\nCohort 1b Placebo\nCohort 1a* RSV\nCohort 1a* Placebo\nCohort 2\nErythema Pain Swelling Arthralgia Fatigue Fever ≥ 38° C Headache Myalgia\nLocal SystemicAny\nPresentation by GSK at ACIP Oct 25, 2023Error bars show 95% CIs for total AEs. Grade 3: >100 mm for erythema and swelling; Grade 3 pain: significant pain at rest; prevents normal \neveryday activities. Fever: temperature ≥38.0 C/100.4 F by any route (oral, axillary or tympanic); Grade 3 fever: >39.0 C/102.2 F.​Grade 3 \nheadache, fatigue, myalgia, arthralgia: preventing normal activitySolicited AEs Reported Within 4 Days of Vaccination (Exposed Set)RSV-OA=ADJ -018 \nCohort 1a: Adults with comorbidities associated with RSV -LRTD \nCohort 1b: Adults without  comorbidities associated with RSV -LRTD \nCohort 2: ≥ 60 YOAGrade 3\nCO-19\n13.1\n0.5 0 013.5\n2.1\n0 014.5\n3.6\n01.010.5\n2.6\n0 0.516.2\n2.4\n00.8\n0255075100\nSAEs pIMDs Unsolicited AEsUnsolicited AEs, SAEs, Fatal SAEs, and pIMDs\nExposed Set\nFatal SAEsCohort 1a: \nAdults with comorbidities \nassociated with RSV -LRTD \nPercent of \nParticipants \n(95% CI)\nPresentation by GSK at ACIP Oct 25, 2023Grade 3: >100 mm for erythema and swelling; Grade 3 pain: significant pain at rest; prevents normal everyday activities. \nFever: temperature ≥38.0 C/100.4 F by any route (oral, axillary or tympanic); Grade 3 fever: >39.0 C/102.2 F. ​Grade 3 headache, fatigue, \nmyalgia, arthralgia: preventing normal activity; SAE; serious adverse events; pIMD , potential immune mediated diseaseWithin 30 days Up to Data Lock Point, September 01, 2023RSVPreF3 + AS01EGrade 3Cohort 1b: \nAdults without  comorbidities \nassociated with RSV -LRTD \nRSVPreF3 + AS01E\nPlaceboRSVPreF3 + AS01E\nPlacebo\n10 1\n2.1\n0.5RSV-OA=ADJ -018 \nCohort 2: \n≥ 60 YOA\nCO-20\nSummary of RSV -OA=ADJ-018 Results\nCO-21\nSummary: Immune Response Among Adults 50 –59 YOA \nNon- inferiority success criteria met in adults 50–59 YOA with and without \ncomorbidities associated with RSV -LRTD compared with adults ≥ 60 YOA\nPresentation by GSK at ACIP Oct 25, 2023\nVaccine efficacy can be inferred in adults 50 –59 YOA, including those with \ncomorbidities associated with RSV -LRTD\nHigh v accine efficacy from pivotal Phase 3 in adults ≥ 60 YOA\nRSV-LRTD = 82.6% for season 1\nSevere RSV-LRTD = 94.1% for season 1\n≥ 1 comorbidity associated with RSV -LRTD = 94.6%\nDurable efficacy across 2 full seasonsRSV-OA=ADJ -018 \nCO-22\nSummary: Immune Response and Safety Among Adults 50 –59 YOA\nNon- inferiority success criteria met in adults 50–59 YOA with and without \ncomorbidities associated with RSV -LRTD compared with adults ≥ 60 YOA\nPresentation by GSK at ACIP Oct 25, 2023\nVaccine efficacy can be inferred in adults 50 –59 YOA, including those with \ncomorbidities associated with RSV -LRTD\nSafety profile for 50 –59 YOA groups consistent with profile observed in \nadults ≥ 60 YOA\nRSV-OA=ADJ -018 \nCO-23\nOverall AREXVY Safety Update\nPresentation by GSK at ACIP Oct 25, 2023\nCO-24\nClinical studies\nAs of Oct. 16, 2023, no reports of ADEM in GSK database\nTwo unconfirmed reports of ADEM in Co- administration Study \n(RSV OA=ADJ -007) with AREXVY + FLU- QIV1\nBoth diagnoses updated by investigator and no longer reported as \nADEM\nPost Authorization \nAs of Oct. 13, 2023, ≥ 2.1 million doses of AREXVY administered* in US\nReported AEs reflect known safety profile**Safety Update\nPresentation by GSK at ACIP Oct 25, 20231. https://clinicaltrials.gov/study/NCT04841577\n*IQVIA NPA Rapid Weekly TRx; **Based on GSK safety database lock Oct. 16 \nADEM, acute disseminated encephalomyelitis\nCO-25\nOverall Summary\nPresentation by GSK at ACIP Oct 25, 2023\nSevere RSV disease among adults 50– 59 YOA with certain comorbidities presents \nsignificant unmet medical need 1\nRSV-OA=ADJ -018 provides data to address this medical need; showing comparable \nimmunogenicity to those ≥ 60 YOA, inferring vaccine efficacy2\nAREXVY is well tolerated with a favorable safety profile in 50– 59 YOA 3\nCO-26\nACIP October 25, 2023\nSusan Gerber, MD\nMedical Director \nPresentation by GSK at ACIP Oct 25, 2023", "summary": "CO-1 ACIP October 25, 2023 Susan Gerber, MD Medical Director  Presentation by GSK at ACIP Oct 25, 2023  CO-2 Substantial RSV Disease Burden and Unmet Medical Need in US  Adults Aged 50 –59 Years  RSV-associated hospitalizations and medically -attended RSV illnesses are  substantial among 50 -59 YOA Published incidence rates likely substantially underestimate RSV burden due to lack  of awareness, standardized testing, and underdetection within surveillance studies Comorbidities associated with…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-25-26-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-10-25-26/02-gerber-adult-RSV-508.pdf", "doc_date": "2023-10-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 26}
{"title": "03 Patton Adult RSV 508", "content": "Centers for Disease Control and Prevention \nNational Center for Immunization and Respiratory Di seases \nPhotographs and images included in this presentation a re licensed solely for CDC/NCIRD online and present ation \nuse. No rights are implied or extended for use in pr inting or any use by other CDC CIOs or any external audiences. \nEpidemiology of Respiratory Syncytial Virus Hospitalizations in Adults — RSV-NET Advisory Committee on Immunization Practices, October 2 5, 2023 \nMonica E. Patton, MD Deputy Lead, RSV-NET Surveillance and Prevention Branch Coronavirus and Other Respiratory Viruses Division \n2RESP-NET: RSV-NET, COVID-NET, FluSurv-NET \nActive, population-based surveillance of laboratory-confirmed RSV-associated hospitalizations \n–>300 acute-care hospitals, 58 counties in 12 states\n–~8.6% of U.S. population \nTests positive for RSV within 14 days prior to or during hospitalization \n–Clinician-driven testing \nClinical data: random sample of RSV-NET patients stratified by age and site RSV-NET: A RESP-NET population-based hospitalizatio n \nsurveillance platform \nCalifornia \nOregon \nUtah \nColorado \nNew Mexico Min nes ota Michigan \nMaryland New York \nConnecticut\nTennessee \nGeorgia \nRSV-NET surveillance areas with percentage of state population represented by participating RSV-NET counties \n\n3Age groups presented today for adults aged ≥18 year s \nAge Group Background/Rationale \n18–49 years Youngest adult group 50–59 years Age group for which we are reviewing dat a today \n60–64 years 60 is youngest age currently recommended for RSV va ccination, with shared clinical \ndecision making, in the U.S. \n65–74 years 65 is a common definition of “older adults” and use d for other vaccine recommendations \n•Certain influenza vaccine formulations \n•Universal pneumococcal vaccination \n•Age of most Medicare eligibility \n≥75 years 75 is the age at which RSV vaccination was recommen ded by the United Kingdom’s Joint \nCommittee on Vaccination and Immunisation (JCVI)* \n*\nhttps://www.gov.uk/government/publications/rsv-immu nisation-programme-jcvi-advice-7-june-2023/respirat ory-syncytial-virus-rsv-immunisation-programme-for- infants-\nand-older-adults-jcvi-full-statement-11-september-2 023 \nEpidemiology of RSV–associated hospitalizations among adults aged 50–59 years \n•Demographics \n•Rates of RSV-associated hospitalizations \n•Underlying medical conditions \n•Severe outcomes (ICU admission, mechanical ventilat ion, death) \n•Comparison of RSV v. influenza v. COVID-19 \n•Will not present rates of RSV-associated hospitaliz ations stratified by risk \nconditions \n5Characteristic Unweighted \nN=17,847 Weighted \n%\nAge (years) 18–49 years 2,435 13.6 \n50–59 years 2,492 14.0 \n60–64 years 1,790 10.0 65–74 years 4,079 22.9 ≥75 years 7,051 39.5 \nRace and ethnicity* White 10,755 62.2 Black 3,529 20.4 \nHispanic 1,434 8.3 Asian or Pacific Islander 1,020 5.9 American Indian or Alaska Native 90 0.5 Multirace 89 0.5 Unknown 367 2.1 Characteristics of non-pregnant adults ≥18 years ho spitalized \nwith lab-confirmed RSV, RSV-NET, 2014–2015 to 2022– 2023 \n*Black, White, American Indian/Alaska Native and As ian/Pacific Islander people were categorized as non -Hispanic; Hispanic people could be of any race. 17,847 hospitalizations over 9 seasons \n14% of \nhospitalizations in adults aged \n50–59 years \n6Adjusted RSV-associated hospitalization rates* per 100,000 adults ≥18 years \nby 5-year age group and year, RSV-NET, 2015–2016 to  2019–2020 \n*Unpublished data. Rates are adjusted for the frequ ency of RSV testing during each season and the sens itivity of RSV diagnostic tests. 0100 200 300 400 500 600 \n18–49 50–54 55–59 60–64 65–69 70–74 75–79 80–84 ≥85 Annual RSV-associated hospitalizations per \n100,000 population 2015–16 2016–17 2017–18 2018–19 2019–20 \n26–59 \n23–42 \n7050 100 150 200 250 \nOct-22 \nNov-22 \nDec-22 \nJan-23 \nFeb-23 \nMar-23 \nApr-23 \nMay-23 \nJun-23 \nJul-23 \nAug-23 \nSep-23 Rate per 100,000 population Unadjusted monthly and cumulative RSV-associated ho spitalization \nrates* among adults ≥18 years — RSV-NET, 2022–2023 \n010 20 30 40 50 60 70 \nMay-22 \nJun-22 \nJul-22 \nAug-22 \nSep-22 \nOct-22 \nNov-22 \nDec-22 \nJan-23 \nFeb-23 \nMar-23 \nApr-23 \nMay-23 \nJun-23 \nJul-23 \nAug-23 \nSep-23 Rate per 100,000 population 18-49 years 50-59 years 60-64 years 65-74 years 75+ years Cumulative rates \nOctober 2022–September 2023 Monthly rates \nMay 2022–September 2023 \n*Rates have not been adjusted for RSV testing pract ices and underestimate actual rates of RSV-associat ed hospitalizations, as not all people hospitalized  with respiratory illness are tested for RSV; clini cian-driven \ntesting practices may differ by disease severity, a ge, and/or racial and ethnic group of patients and may have changed over time.\n8Underlying medical conditions* among non-pregnant a dults ≥18 years with RSV-\nassociated hospitalizations — RSV-NET, 2014–2015 to 2017–2018 and 2022–2023 \nMajor underlying condition categories Unweighted \nN=7,479 Weighted \n%\nCardovascular disease (overall) 5,141 57.4 Obesity 2,798 39.0 \nDiabetes 2,484 34.1 \nCOPD 2,248 31.4 \nHeart failure 1,984 28.0 \nChronic kidney disease 2,003 27.0 \nAsthma 1,789 24.0 \nCoronary artery disease (includes CABG, MI) 1,718 24. 0 \nNeurologic condition 1,628 22.6 \nImmune compromised 1,567 20.8 \nChronic metabolic disease, not including diabetes 1, 417 19.3 \nOther chronic lung disease 995 17.1 \nChronic liver disease 538 7.2 \nAutoimmune/inflammatory disease 310 4.5 Blood disorders 287 4.1 94.3% of adults ≥18 years with RSV-associated hospitalization had at least one underlying medical condition: •31.4%: 1–2 conditions \n•62.9%: ≥3 conditions \n*Clinical data, including underlying medical condit ions, were collected for all patients with laborato ry-confirmed RSV hospitalizations during the 2014–2 015 to 2017–2018 seasons, and for an \nage- and site-stratified random sample of patients w ith laboratory-confirmed RSV hospitalizations durin g the 2022–2023 season. Data are presented as unwei ghted case counts and weighted \npercentages that were weighted for the probability of selection. \n9Underlying medical conditions* among non-pregnant a dults ≥18 years with RSV-\nassociated hospitalizations — RSV-NET, 2014–2015 to 2017–2018 and 2022–2023 \nMajor underlying condition categories Unweighted \nN=7,479 Weighted \n%\nCardovascular disease (overall) 5,141 57.4 Obesity 2,798 39.0 \nDiabetes 2,484 34.1 \nCOPD 2,248 31.4 \nHeart failure 1,984 28.0 \nChronic kidney disease 2,003 27.0 \nAsthma 1,789 24.0 \nCoronary artery disease (includes CABG, MI) 1,718 24. 0 \nNeurologic condition 1,628 22.6 \nImmune compromised 1,567 20.8 \nChronic metabolic disease, not including diabetes 1, 417 19.3 \nOther chronic lung disease 995 17.1 \nChronic liver disease 538 7.2 \nAutoimmune/inflammatory disease 310 4.5 Blood disorders 287 4.1 94.3% of adults ≥18 years with RSV-associated hospitalization had at least one underlying medical condition: •31.4%: 1–2 conditions \n•62.9%: ≥3 conditions \n*Clinical data, including underlying medical condit ions, were collected for all patients with laborato ry-confirmed RSV hospitalizations during the 2014–2 015 to 2017–2018 seasons, and for an \nage- and site-stratified random sample of patients w ith laboratory-confirmed RSV hospitalizations durin g the 2022–2023 season. Data are presented as unwei ghted case counts and weighted \npercentages that were weighted for the probability of selection. \n100 20 40 60 80 100 No medical condition \n≥1 medical condition \n1-2 conditions \n>=3 conditions \nObesity \nCardovascular disease… \nDiabetes \nCOPD \nAsthma \nImmune compromised \nHeart failure \nChonic kidney disease \nNeurologic condition \nCoronary artery disease… \nChronic metabolic disease,… \nOther chronic lung disease \nChronic liver disease \nBlood disorders \nAutoimmune/inflammatory… Frequency of underlying medical conditions among no n-pregnant adults with RSV-\nassociated hospitalizations by age group — RSV-NET, 2014–2015 to 2017–2018 and \n2022–2023 \n*Clinical data were collected for all patients with l aboratory-confirmed RSV hospitalizations during the 2014 –2015 to 2017–2018 seasons, and for an age- and site-st ratified random sample of patients with laboratory-confi rmed RSV hospitalizations during the \n2022–2023 season. Displayed percentages were weighte d for the probability of selection. 18–49 years \n0 20 40 60 80 100 50–59 years \n0 20 40 60 80 100 60–64 years \n0 20 40 60 80 100 65–74 years \n0 20 40 60 80 100 120 ≥75 years \nPercent Percent Percent Percent Percent \n1114 \n0 20 40 60 80 100 No medical condition \n≥1 medical condition \n1-2 conditions \n>=3 conditions \nObesity \nCardovascular disease… \nDiabetes \nCOPD \nAsthma \nImmune compromised \nHeart failure \nChonic kidney disease \nNeurologic condition \nCoronary artery disease… \nChronic metabolic disease,… \nOther chronic lung disease \nChronic liver disease \nBlood disorders \nAutoimmune/inflammatory… Frequency of underlying medical conditions among no n-pregnant adults with RSV-\nassociated hospitalizations by age group — RSV-NET, 2014–2015 to 2017–2018 and \n2022–2023 \n18–49 years \n4\n0 20 40 60 80 100 50–59 years \n4\n0 20 40 60 80 100 60–64 years \n4\n0 20 40 60 80 100 65–74 years \n4\n0 20 40 60 80 100 120 ≥75 years \n*Clinical data were collected for all patients with  laboratory-confirmed RSV hospitalizations during t he 2014–2015 to 2017–2018 seasons, and for an age- a nd site-stratified random sample of patients with l aboratory-confirmed RSV hospitalizations during the 2022–2023 season. Displayed \npercentages were weighted for the probability of se lection. Percent Percent Percent Percent Percent \n1286 \n0 20 40 60 80 100 No medical condition \n≥1 medical condition \n1-2 conditions \n>=3 conditions \nObesity \nCardovascular disease… \nDiabetes \nCOPD \nAsthma \nImmune compromised \nHeart failure \nChonic kidney disease \nNeurologic condition \nCoronary artery disease… \nChronic metabolic disease,… \nOther chronic lung disease \nChronic liver disease \nBlood disorders \nAutoimmune/inflammatory… Frequency of underlying medical conditions among no n-pregnant adults with RSV-\nassociated hospitalizations by age group — RSV-NET, 2014–2015 to 2017–2018 and \n2022–2023 \n18–49 years \n96 \n0 20 40 60 80 100 50–59 years \n96 \n0 20 40 60 80 100 60–64 years \n96 \n0 20 40 60 80 100 65–74 years \n96 \n0 20 40 60 80 100 120 ≥75 years \n*Clinical data were collected for all patients with  laboratory-confirmed RSV hospitalizations during t he 2014–2015 to 2017–2018 seasons, and for an age- a nd site-stratified random sample of patients with l aboratory-confirmed RSV hospitalizations during the 2022–2023 season. Displayed \npercentages were weighted for the probability of se lection. Percent Percent Percent Percent Percent \n1344 \n0 20 40 60 80 100 No medical condition \n≥1 medical condition \n1-2 conditions \n>=3 conditions \nObesity \nCardovascular disease… \nDiabetes \nCOPD \nAsthma \nImmune compromised \nHeart failure \nChonic kidney disease \nNeurologic condition \nCoronary artery disease… \nChronic metabolic disease,… \nOther chronic lung disease \nChronic liver disease \nBlood disorders \nAutoimmune/inflammatory… Frequency of underlying medical conditions among no n-pregnant adults with RSV-\nassociated hospitalizations by age group — RSV-NET, 2014–2015 to 2017–2018 and \n2022–2023 \n18–49 years \n38 \n0 20 40 60 80 100 50–59 years \n33 \n0 20 40 60 80 100 60–64 years \n27 \n0 20 40 60 80 100 65–74 years \n26 \n0 20 40 60 80 100 120 ≥75 years \n*Clinical data were collected for all patients with  laboratory-confirmed RSV hospitalizations during t he 2014–2015 to 2017–2018 seasons, and for an age- a nd site-stratified random sample of patients with l aboratory-confirmed RSV hospitalizations during the 2022–2023 season. Displayed \npercentages were weighted for the probability of se lection. Percent Percent Percent Percent Percent \n1442 \n0 20 40 60 80 100 No medical condition \n≥1 medical condition \n1-2 conditions \n>=3 conditions \nObesity \nCardovascular disease… \nDiabetes \nCOPD \nAsthma \nImmune compromised \nHeart failure \nChonic kidney disease \nNeurologic condition \nCoronary artery disease… \nChronic metabolic disease,… \nOther chronic lung disease \nChronic liver disease \nBlood disorders \nAutoimmune/inflammatory… Frequency of underlying medical conditions among no n-pregnant adults with RSV-\nassociated hospitalizations by age group — RSV-NET, 2014–2015 to 2017–2018 and \n2022–2023 \n18–49 years \n58 \n0 20 40 60 80 100 50–59 years \n63 \n0 20 40 60 80 100 60–64 years \n69 \n0 20 40 60 80 100 65–74 years \n69 \n0 20 40 60 80 100 120 ≥75 years \n*Clinical data were collected for all patients with  laboratory-confirmed RSV hospitalizations during t he 2014–2015 to 2017–2018 seasons, and for an age- a nd site-stratified random sample of patients with l aboratory-confirmed RSV hospitalizations during the 2022–2023 season. Displayed \npercentages were weighted for the probability of se lection.Percent Percent Percent Percent Percent \n1553 \n0 20 40 60 80 100 No medical condition \n≥1 medical condition \n1-2 conditions \n>=3 conditions \nObesity \nCardovascular disease… \nDiabetes \nCOPD \nAsthma \nImmune compromised \nHeart failure \nChonic kidney disease \nNeurologic condition \nCoronary artery disease… \nChronic metabolic disease,… \nOther chronic lung disease \nChronic liver disease \nBlood disorders \nAutoimmune/inflammatory… Frequency of underlying medical conditions among no n-pregnant adults with RSV-\nassociated hospitalizations by age group — RSV-NET, 2014–2015 to 2017–2018 and \n2022–2023 \n18–49 years \n44 \n0 20 40 60 80 100 50–59 years \n49 \n0 20 40 60 80 100 60–64 years \n62 \n0 20 40 60 80 100 65–74 years \n75 \n0 20 40 60 80 100 120 ≥75 years \n*Clinical data were collected for all patients with  laboratory-confirmed RSV hospitalizations during t he 2014–2015 to 2017–2018 seasons, and for an age- a nd site-stratified random sample of patients with l aboratory-confirmed RSV hospitalizations during the 2022–2023 season. Displayed \npercentages were weighted for the probability of se lection. Percent Percent Percent Percent Percent \n1653 \n32 \n0 20 40 60 80 100 No medical condition \n≥1 medical condition \n1-2 conditions \n>=3 conditions \nObesity \nCardovascular disease… \nDiabetes \nCOPD \nAsthma \nImmune compromised \nHeart failure \nChonic kidney disease \nNeurologic condition \nCoronary artery disease… \nChronic metabolic disease,… \nOther chronic lung disease \nChronic liver disease \nBlood disorders \nAutoimmune/inflammatory… Frequency of underlying medical conditions among no n-pregnant adults with RSV-\nassociated hospitalizations by age group — RSV-NET, 2014–2015 to 2017–2018 and \n2022–2023 \n18–49 years \n44 \n43 \n0 20 40 60 80 100 50–59 years \n44 \n49 \n0 20 40 60 80 100 60–64 years \n47 \n62 \n0 20 40 60 80 100 65–74 years \n75 \n36 \n0 20 40 60 80 100 120 ≥75 years \n*Clinical data were collected for all patients with  laboratory-confirmed RSV hospitalizations during t he 2014–2015 to 2017–2018 seasons, and for an age- a nd site-stratified random sample of patients with l aboratory-confirmed RSV hospitalizations during the 2022–2023 season. Displayed \npercentages were weighted for the probability of se lection. Percent Percent Percent Percent Percent \n1753 \n32 \n25 \n0 20 40 60 80 100 No medical condition \n≥1 medical condition \n1-2 conditions \n>=3 conditions \nObesity \nCardovascular disease… \nDiabetes \nCOPD \nAsthma \nImmune compromised \nHeart failure \nChonic kidney disease \nNeurologic condition \nCoronary artery disease… \nChronic metabolic disease,… \nOther chronic lung disease \nChronic liver disease \nBlood disorders \nAutoimmune/inflammatory… Frequency of underlying medical conditions among no n-pregnant adults with RSV-\nassociated hospitalizations by age group — RSV-NET, 2014–2015 to 2017–2018 and \n2022–2023 \n18–49 years \n44 \n43 \n37 \n0 20 40 60 80 100 50–59 years \n44 \n49 \n41 \n0 20 40 60 80 100 60–64 years \n47 \n62 \n42 \n0 20 40 60 80 100 65–74 years \n75 \n33 \n36 \n33 \n0 20 40 60 80 100 120 ≥75 years \n*Clinical data were collected for all patients with  laboratory-confirmed RSV hospitalizations during t he 2014–2015 to 2017–2018 seasons, and for an age- a nd site-stratified random sample of patients with l aboratory-confirmed RSV hospitalizations during the 2022–2023 season. Displayed \npercentages were weighted for the probability of se lection. Percent Percent Percent Percent Percent \n18Prevalence of certain medical conditions *among non-pregnant adults with RSV-\nassociated hospitalizations (RSV-NET, 2014–2015 to 2017–2018 and 2022–2023) and \namong the general population (National Center for H ealth Statistics †, 2022) by age \ngroup \n*Clinical data were collected for all patients with  laboratory-confirmed RSV hospitalizations during t he 2014–2015 to 2017–2018 seasons, and for an age- a nd site-stratified random sample of patients with l aboratory-confirmed RSV \nhospitalizations during the 2022–2023 season. Displ ayed percentages were weighted for the probability of selection. \n†National Center for Health Statistics. United State s, 2022. National Health Interview Survey. Generated interactively: Oct 17, 2023 from https://wwwn.cdc.gov/NHISDataQueryTool/SHS_adult/ind ex.html 50–64 years ≥65 years \nGeneral \npopulation RSV-NET RSV-\nNET/ \nPop General \npopulation RSV-NET RSV-\nNET/ \nPop Condition % (95% CI) % (95% CI) % (95% CI) % (95% CI) \nCoronary artery disease 5.0 (4.4, 5.6) 18.9 (16.9, 21.0) 3.8 15.3 (14.4, 16.2) 31.3 (29.1, 33.6) 2.0 \nCOPD 6.2 (5.5, 6.9) 35.4 (32.9, 37.9) 5.7 9.8 (9.1, 10.5) 33.2 (30.1, 35.5) 3.4 \nDiabetes mellitus 13.8 (12.9, 14.7) 37.7 (35.1, 40.4) 2.7 20.1 (19.1, 21.1) 31.8 (29.6, 34.1) 1.6 \nAsthma 9.1 (8.4, 9.9) 28.6 (26.3, 31.0) 3.1 8.0 (7.3, 8.6) 17.6 (15.8, 19.4) 2.2 \nObesity 37.6 (36.2, 38.9) 46.4 (43.7, 49.0) 1.2 30.4 (29.2, 31.6) 28.4 (26.1, 30.8) 0.9 \n19Frequency of underlying medical conditions among ad ults aged 50–59 years with ICU \nadmissions and RSV-associated hospitalizations — RSV -NET, 2014–2015 to 2017–2018 and \n2022–2023 \nICU admissions Hospitalizations \n*Clinical data were collected for all patients with  laboratory-confirmed RSV hospitalizations during t he 2014–2015 to 2017–2018 seasons, and for an age- a nd site-stratified random sample of patients with l aboratory-confirmed RSV hospitalizations during the 2022–2023 season. Displayed \npercentages were weighted for the probability of se lection. 0 20 40 60 80 100 No medical condition \n≥1 medical condition \nCardovascular disease (overall) \nObesity \nDiabetes \nCOPD \nHeart failure \nImmune compromised \nChonic kidney disease \nAsthma \nCoronary artery disease (includes CABG, MI) \nOther chronic lung disease \nNeurologic condition \nChronic liver disease \nChronic metabolic disease, not including diabetes \nBlood disorders \nAutoimmune/inflammatory disease \n0 20 40 60 80 100 No medical condition \n≥1 medical condition \nObesity \nCardovascular disease (overall) \nDiabetes \nCOPD \nAsthma \nImmune compromised \nHeart failure \nChonic kidney disease \nNeurologic condition \nCoronary artery disease (includes CABG, MI) \nChronic metabolic disease, not including diabetes \nOther chronic lung disease \nChronic liver disease \nBlood disorders \nAutoimmune/inflammatory disease \nPercent Percent \n20Frequency of underlying medical conditions among ad ults aged 50–59 years with ICU \nadmissions and RSV-associated hospitalizations — RSV -NET, 2014–2015 to 2017–2018 and \n2022–2023 \nICU admissions Hospitalizations \n*Clinical data were collected for all patients with  laboratory-confirmed RSV hospitalizations during t he 2014–2015 to 2017–2018 seasons, and for an age- a nd site-stratified random sample of patients with l aboratory-confirmed RSV hospitalizations during the 2022–2023 season. Displayed \npercentages were weighted for the probability of se lection. 4\n95 \n49 \n44 \n40 \n35 \n30 \n29 \n26 \n25 \n19 \n17 \n16 \n14 \n11 \n4\n2\n0 20 40 60 80 100 No medical condition \n≥1 medical condition \nCardovascular disease (overall) \nObesity \nDiabetes \nCOPD \nHeart failure \nImmune compromised \nChonic kidney disease \nAsthma \nCoronary artery disease (includes CABG, MI) \nOther chronic lung disease \nNeurologic condition \nChronic liver disease \nChronic metabolic disease, not including diabetes \nBlood disorders \nAutoimmune/inflammatory disease 4\n96 \n44 \n43 \n37 \n31 \n29 \n26 \n23 \n21 \n17 \n17 \n15 \n12 \n10 \n5\n4\n0 20 40 60 80 100 No medical condition \n≥1 medical condition \nObesity \nCardovascular disease (overall) \nDiabetes \nCOPD \nAsthma \nImmune compromised \nHeart failure \nChonic kidney disease \nNeurologic condition \nCoronary artery disease (includes CABG, MI) \nChronic metabolic disease, not including diabetes \nOther chronic lung disease \nChronic liver disease \nBlood disorders \nAutoimmune/inflammatory disease \nPercent Percent \n21Frequency of underlying medical conditions among ad ults aged 50–59 years with ICU \nadmissions and RSV-associated hospitalizations — RSV -NET, 2014–2015 to 2017–2018 and \n2022–2023 \nICU admissions Hospitalizations \n*Clinical data were collected for all patients with  laboratory-confirmed RSV hospitalizations during t he 2014–2015 to 2017–2018 seasons, and for an age- a nd site-stratified random sample of patients with l aboratory-confirmed RSV hospitalizations during the 2022–2023 season. Displayed \npercentages were weighted for the probability of se lection. 4\n95 \n49 \n44 \n40 \n35 \n30 \n29 \n26 \n25 \n19 \n17 \n16 \n14 \n11 \n4\n2\n0 20 40 60 80 100 No medical condition \n≥1 medical condition \nCardovascular disease (overall) \nObesity \nDiabetes \nCOPD \nHeart failure \nImmune compromised \nChonic kidney disease \nAsthma \nCoronary artery disease (includes CABG, MI) \nOther chronic lung disease \nNeurologic condition \nChronic liver disease \nChronic metabolic disease, not including diabetes \nBlood disorders \nAutoimmune/inflammatory disease 4\n96 \n44 \n43 \n37 \n31 \n29 \n26 \n23 \n21 \n17 \n17 \n15 \n12 \n10 \n5\n4\n0 20 40 60 80 100 No medical condition \n≥1 medical condition \nObesity \nCardovascular disease (overall) \nDiabetes \nCOPD \nAsthma \nImmune compromised \nHeart failure \nChonic kidney disease \nNeurologic condition \nCoronary artery disease (includes CABG, MI) \nChronic metabolic disease, not including diabetes \nOther chronic lung disease \nChronic liver disease \nBlood disorders \nAutoimmune/inflammatory disease \nPercent Percent \n22Percentages of non-pregnant adults ≥18 years with R SV-associated \nhospitalization who experienced severe outcomes by a ge group, RSV-NET, \n2022–2023 \n16% 21% \n16% 21% \n15% \n4% 10% \n4% 6% \n4% \n2% 3% \n2% 4% 6% \n0% 5% 10% 15% 20% 25% \n18–49 50–59 60–64 65–74 ≥75 Proportion of Hospitalized Adults with Severe \nOutcome ICU Mechanical ventilation Died \nICU = intensive care unit *Clinical data, including severe outcomes, were col lected for an age- and site-stratified random sample  of patients with laboratory-confirmed RSV hospital izations during the 2022–2023 season. \nDisplayed percentages were weighted for the probabi lity of selection. \n2316 21 \n16 21 \n15 17 18 \n18 \n17 \n11 16 21 \n20 \n19 \n11 \n0510 15 20 25 \n18–49 50–59 60–64 65–74 ≥75 Proportion of Hospitalizations Admitted to ICU RSV Influenza COVID Percentages of non-pregnant adults ≥18 years with l aboratory-confirmed \nhospitalization admitted to intensive care unit (ICU) , RSV-NET, FluSurv-NET, \nCOVID-NET, 2022–2023 \n*Clinical data, including severe outcomes, were coll ected for an age- and site-stratified random sample of patients with laboratory-confirmed RSV, Influenz a, and COVID-19 hospitalizations during the 2022–20 23 season. Displayed percentages \nwere weighted for the probability of selection. †Patients with severe disease may be more likely to b e tested for RSV, Influenza, or COVID-19 which may overestimate proportions of patients admitted to the  ICU. \n‡Data shown here does not take patient vaccination or  treatment status into account. \n§FluSurv-NET surveillance occurred during October 202 2–April 2023; RSV-NET and COVID-NET surveillance occ urred year-round. \n2423\n246\n13\n335\n1346\n4\n01234567\n18–49 50–59 60–64 65–74 ≥75 Proportion of Hospitalizatizations with In-hospital  \nDeath RSV Influenza COVID Percentages of non-pregnant adults ≥18 years with l aboratory-confirmed \nhospitalization with in-hospital death *, RSV-NET, FluSurv-NET, COVID-NET, \n2022–2023 \n*Clinical data, including severe outcomes, were coll ected for an age- and site-stratified random sample of patients with laboratory-confirmed RSV, Influenz a, and COVID-19 hospitalizations during the 2022–20 23 season. Displayed percentages \nwere weighted for the probability of selection. †Patients with severe disease may be more likely to b e tested for RSV, Influenza, or COVID-19 which may overestimate proportions of patients admitted to the  ICU. \n‡Data shown here does not take patient vaccination or  treatment status into account. \n§FluSurv-NET surveillance occurred during October 202 2–April 2023; RSV-NET and COVID-NET surveillance occ urred year-round. \n25Distribution of RSV-associated hospitalizations and  severe outcomes \namong adults ≥18 years by age group, RSV-NET, 2022–2 023 \n17% 15% 13% 8% 12% 14% 22% \n9% 9% 9% 7% \n4% 23% 28% 26% \n22% 39% 33% 31% \n58% \n0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% \nHospitalizations ICU Mechanical ventilation Death Proportion 18–49 50–59 60–64 65–74 ≥75 \nICU = intensive care unit *Clinical data, including severe outcomes, were col lected for an age- and site-stratified random sample  of patients with laboratory-confirmed RSV hospital izations during the 2022–2023 \nseason. Displayed percentages were weighted for the  probability of selection. \n26Distribution of RSV-associated hospitalizations and  severe outcomes \namong adults ≥18 years by age group, RSV-NET, 2022–2 023 \n17% 15% 13% 8% 12% 14% 22% \n9% 9% 9% 7% \n4% 23% 28% 26% \n22% 39% 33% 31% \n58% \n0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% \nHospitalizations ICU Mechanical ventilation Death Proportion 18–49 50–59 60–64 65–74 ≥75 \nICU = intensive care unit *Clinical data, including severe outcomes, were col lected for an age- and site-stratified random sample  of patients with laboratory-confirmed RSV hospital izations during the 2022–2023 \nseason. Displayed percentages were weighted for the  probability of selection. \n27Distribution of RSV-associated hospitalizations and  severe outcomes \namong adults ≥18 years by age group, RSV-NET, 2022–2 023 \n17% 15% 13% 8% 12% 14% 22% \n9% 9% 9% 7% \n4% 23% 28% 26% \n22% 39% 33% 31% \n58% \n0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% \nHospitalizations ICU Mechanical ventilation Death Proportion 18–49 50–59 60–64 65–74 ≥75 \nICU = intensive care unit *Clinical data, including severe outcomes, were col lected for an age- and site-stratified random sample  of patients with laboratory-confirmed RSV hospital izations during the 2022–2023 \nseason. Displayed percentages were weighted for the  probability of selection. \n28Distribution of RSV-associated hospitalizations and  severe outcomes \namong adults ≥18 years by age group, RSV-NET, 2022–2 023 \n17% 15% 13% 8% 12% 14% 22% \n9% 9% 9% 7% \n4% 23% 28% 26% \n22% 39% 33% 31% \n58% \n0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% \nHospitalizations ICU Mechanical ventilation Death Proportion 18–49 50–59 60–64 65–74 ≥75 \nICU = intensive care unit *Clinical data, including severe outcomes, were col lected for an age- and site-stratified random sample  of patients with laboratory-confirmed RSV hospital izations during the 2022–2023 \nseason. Displayed percentages were weighted for the  probability of selection. \n29Median age of non-pregnant adults ≥18 years with RS V-associated \nhospitalizations by race and ethnicity* — RSV-NET, 2 014–2015 to 2022–\n2023 \nUnweighted Weighted \n%Median Age Interquartile \nrange (IQR) \nOverall 17,847 - 69 (58–81) \nWhite 10,755 62.2 73 (63-82) \nBlack 3,529 20.4 62 (50-71) \nHispanic 1,434 8.3 62 (48-76) \nAsian or Pacific Islander 1,020 5.9 73 (59-83) \nAmerican Indian or Alaska Native 90 0.5 64 (54-73) \nMultirace 89 0.5 75 (58-84) \nUnknown 367 2.1 68 (57-78) \n*Black, White, American Indian/Alaska Native and As ian/Pacific Islander people were categorized as non -Hispanic; Hispanic people could be of any race. \n30Median age of non-pregnant adults ≥18 years with RS V-associated \nhospitalizations by race and ethnicity* — RSV-NET, 2 014–2015 to 2022–\n2023 \nUnweighted Weighted \n%Median Age Interquartile \nrange (IQR) \nOverall 17,847 - 69 (58–81) \nWhite 10,755 62.2 73 (63-82) \nBlack 3,529 20.4 62 (50-71) \nHispanic 1,434 8.3 62 (48-76) \nAsian or Pacific Islander 1,020 5.9 73 (59-83) \nAmerican Indian or Alaska Native 90 0.5 64 (54-73) \nMultirace 89 0.5 75 (58-84) \nUnknown 367 2.1 68 (57-78) \n*Black, White, American Indian/Alaska Native and As ian/Pacific Islander people were categorized as non -Hispanic; Hispanic people could be of any race. \n31Distribution of RSV-associated hospitalizations amon g adults ≥18 years by \nrace and ethnicity *and age group— RSV-NET, 2014–2015 to 2022–2023 \n39% 53% 62% 69% 79% 29% 23% 21% 17% 7% \n18% 13% 8% 6% 5% 8% 6% 5% 5% 6% \n0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% \n18–49 50–59 60–64 65–74 ≥75 Proportion White Black Hispanic Asian or Pacific Islander \n*Black, White, and Asian/Pacific Islander people we re categorized as non-Hispanic; Hispanic people cou ld be of any race. American Indian/Alaska Native pe rsons are not shown \ndue to small numbers. \n32Distribution of RSV-associated ICU admissions among ad ults ≥18 years by \nrace and ethnicity * and age group — RSV-NET, 2014–2015 to 2022–2023 \n41% 60% 58% 69% 75% 39% 22% 30% 19% 9% 11% 8% 8% 6% 8% 9% 9% 5% 5% 8% \n0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% \n18–49 50–59 60–64 65–74 ≥75 Proportion White Black Hispanic Asian or Pacific Islander \n*Black, White, and Asian/Pacific Islander people we re categorized as non-Hispanic; Hispanic people cou ld be of any race. American Indian/Alaska Native pe rsons are not shown \ndue to small numbers. \n33Burden-adjusted hospitalization rate ratios among ad ults ≥18 years by race \nand ethnicity* — RSV-NET, 2016–2017 to 2019–2020 \nMaximum rate ratio (2016–17 to 2019–20) \nAverage rate ratio (2016–17 to 2019–20) Minimum rate ratio (2016–17 to 2019–20) \n01234\n18–49 50–59 60–64 65–74 ≥75 White \nMaximum rate ratio (2016–17 to 2019–20) \nAverage rate ratio (2016–17 to 2019–20) Minimum rate ratio (2016–17 to 2019–20) \n*Black, White, American Indian/Alaska Native and As ian/Pacific Islander people were categorized as non -Hispanic; Hispanic people could be of any race. \n34\n01234\n18–49 50–59 60–64 65–74 ≥75 White Hispanic Burden-adjusted hospitalization rate ratios among ad ults ≥18 years by race \nand ethnicity* — RSV-NET, 2016–2017 to 2019–2020 \nMaximum rate ratio (2016–17 to 2019–20) \nAverage rate ratio (2016–17 to 2019–20) Minimum rate ratio (2016–17 to 2019–20) \n*Black, White, American Indian/Alaska Native and As ian/Pacific Islander people were categorized as non -Hispanic; Hispanic people could be of any race. \n35\n01234\n18–49 50–59 60–64 65–74 ≥75 Asian or Pacific Islander White Hispanic Burden-adjusted hospitalization rate ratios among ad ults ≥18 years by race \nand ethnicity* — RSV-NET, 2016–2017 to 2019–2020 \nMaximum rate ratio (2016–17 to 2019–20) \nAverage rate ratio (2016–17 to 2019–20) Minimum rate ratio (2016–17 to 2019–20) \n*Black, White, American Indian/Alaska Native and As ian/Pacific Islander people were categorized as non -Hispanic; Hispanic people could be of any race. \n36Maximum rate ratio (2016–17 to 2019–20) \nAverage rate ratio (2016–17 to 2019–20) Minimum rate ratio (2016–17 to 2019–20) \n01234\n18–49 50–59 60–64 65–74 ≥75 Asian or Pacific Islander White Hispanic Black Burden-adjusted hospitalization rate ratios among ad ults ≥18 years by race \nand ethnicity* — RSV-NET, 2016–2017 to 2019–2020 \nMaximum rate ratio (2016–17 to 2019–20) \nAverage rate ratio (2016–17 to 2019–20) Minimum rate ratio (2016–17 to 2019–20) \n*Black, White, American Indian/Alaska Native and As ian/Pacific Islander people were categorized as non -Hispanic; Hispanic people could be of any race. \n37\n01234\n18–49 50–59 60–64 65–74 ≥75 Asian or Pacific Islander White Hispanic Black American Indian or Alaska Native \nMaximum rate ratio (2016–17 to 2019–20) \nAverage rate ratio (2016–17 to 2019–20) Minimum rate ratio (2016–17 to 2019–20) Burden-adjusted hospitalization rate ratios among ad ults ≥18 years by race \nand ethnicity* — RSV-NET, 2016–2017 to 2019–2020 \n*Black, White, American Indian/Alaska Native and As ian/Pacific Islander people were categorized as non -Hispanic; Hispanic people could be of any race. \n38Coronavirus and Other Respiratory \nViruses Division \nAmadea Britton Fiona Havers Michael Melgar Kadam Patel Huong Pham Chris Taylor Michael Whitaker Influenza Division \nAlissa O’Halloran Catherine Bozio Dawud Ujamaa RESP-NET Site Investigators and Staff Acknowledgements \nFor more information, contact CDC 1-800-CDC-INFO (232-4636) TTY:  1-888-232-6348    www.cdc.gov \nThe findings and conclusions in this report are tho se of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Pre vention. \nPhotographs and images included in this presentatio n are licensed solely for CDC/NCIRD online and pres entation \nuse. No rights are implied or extended for use in p rinting or any use by other CDC CIOs or any externa l audiences.", "summary": "Centers for Disease Control and Prevention  National Center for Immunization and Respiratory Di seases  Photographs and images included in this presentation a re licensed solely for CDC/NCIRD online and present ation  use. No rights are implied or extended for use in pr inting or any use by other CDC CIOs or any external audiences.  Epidemiology of Respiratory Syncytial Virus Hospitalizations in Adults — RSV-NET Advisory Committee on Immunization Practices, October 2 5, 2023  Monica E. Patton,…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-25-26-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-10-25-26/03-Patton-Adult-RSV-508.pdf", "doc_date": "2023-10-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 39}
{"title": "04 Britton Adult RSV 508", "content": "Centers for Disease Control and Prevention \nNational Center for Immunization and Respiratory Di seases \nPhotographs and images included in this presentation a re licensed solely for CDC/NCIRD online and present ation \nuse. No rights are implied or extended for use in pr inting or any use by other CDC CIOs or any external audiences. \nACIP Adult RSV Work Group Considerations \nRespiratory Syncytial Virus (RSV) in Adults Use of RSV vaccines in adults aged 50–59 years \nAmadea Britton, MD, MS Advisory Committee on Immunization Practices October 25, 2023 \nReview current recommendation for use of RSV vaccin es in adults aged 60 years and \nolder \nSummarize available safety and immunogenicity data on the use of RSVPreF3 vaccine \nin adults aged 50–59 years \nShare preliminary Adult RSV Work Group interpretati ons on the use of RSV vaccines in \nadults aged 50–59 years and upcoming policy decisio ns Overview \n2\nReview of current ACIP recommendation for use of RSV vaccines in adults aged 60 years and older\nRSVPreF3 ( Arexvy, GSK ) is a 1-dose adjuvanted (AS01 E) recombinant \nprefusion F protein (preF) vaccine. \nRSVpreF ( Abrysvo, Pfizer ) is a 1-dose recombinant preF vaccine.* In June 2023, ACIP and CDC recommended the first two  RSV \nvaccines for older adults. \n*The same vaccine formulation is FDA-approved and C DC-recommended for vaccination of pregnant persons for RSV prevention in infants. \nhttps://www.cdc.gov/mmwr/volumes/72/wr/mm7229a4.htm4\nGSK’s adjuvanted RSVPreF3 and Pfizer’s RSVpreF vaccin es both \ndemonstrated significant efficacy against lower respiratory tract disease \ncaused by RSV among older adults over at least two seas ons. \n–Trials were underpowered to show efficacy in the olde st adults and in frail adults \n–Trials were underpowered to show efficacy against RSV  hospitalization, although efficacy \nagainst symptomatic illness may indicate efficacy aga inst more severe disease \nAcknowledging these limitations, the Work Group and ACI P felt that RSV \nvaccination had the potential to prevent considerable mor bidity from RSV \ndisease among older adults. Vaccine Efficacy \nhttps://www.cdc.gov/vaccines/acip/meetings/download s/slides-2023-06-21-23/06-RSV-Adults-Melgar-508.pdf5\nSix cases of inflammatory neurologic events (includin g Guillain-Barré \nsyndrome) were reported across trials in older adults within 6 weeks after \nRSV vaccination, compared with no cases within 6 weeks  after placebo. \n–3 cases after vaccination with GSK’s RSVPreF3* \n–3 cases after vaccination with Pfizer’s RSVpreF \nImbalance in the small number of atrial fibrillation e vents; more cases \namong vaccine recipients, compared with placebo recip ients. \nIt is unknown at this time whether these events occurred b y chance, or \nwhether RSV vaccination increases the risk of these eve nts. Vaccine Safety \nhttps://www.cdc.gov/mmwr/volumes/72/wr/mm7229a4.htm\n* Two of the 3 reported inflammatory neurologic eve nts after vaccination with GSK’s RSVPreF3 were repo rted as acute disseminated encephalomyelitis (ADEM)  in \nparticipants that simultaneously received RSVPreF3 vaccine and standard dose seasonal influenza vaccin e. The site investigator that initially reported th e cases has \nsince revised the diagnosis in both cases (from ADE M to hypoglycemia and dementia, and from ADEM to st roke). FDA’s package insert for RSVPreF3 vaccine continues \nto list these as Serious Adverse Events. 6\nIn June, the Adult RSV Work Group proposed: \n–A universal recommendation for RSV vaccination in ad ults 65 and older \n–RSV vaccination in adults aged 60–64 years, using s hared clinical decision-making \nDuring ACIP deliberations an amendment was proposed a nd accepted for \nthe following recommendation: \n–Adults ages 60 years and older (both those 60–64 and 65  and older) may receive a single \ndose of RSV vaccine using shared clinical-decision maki ng. \nThe shared clinical decision-making recommendation w as intended to \nallow flexibility for providers and patients to conside r individual risk for \nRSV disease and target RSV vaccination to those most like ly to benefit. ACIP deliberations leading to a recommendation on t he use \nof RSV vaccine in adults 60 and older \nACIP Adult RSV Session. June 21, 2023. Webcast: htt ps://www.youtube.com/watch?v=DunxtgBmRxI&list=PLvrp 9iOIL TQb6D9e1YZWpbUvzfptNMKx2&index=20 7\nChronic underlying medical conditions associated with increased risk of severe RSV disease \nLung disease \nCardiovascular disease \nModerate or severe immune compromise \nDiabetes Mellitus \nOther conditions that might increase the risk for severe disease Neurologic or neuromuscular conditions \nKidney disorders \nHematologic disorders \nLiver disorders \nhttps://www.cdc.gov/mmwr/volumes/72/wr/mm7229a4.htm\n8\nOther factors associated with increased risk of severe RSV disease \nResidence in a nursing home or other long-term care facility (L TCF) \nFrailty \nAdvanced age \nhttps://www.cdc.gov/mmwr/volumes/72/wr/mm7229a4.htm9\nNext steps: new data on the safety and immunogenicity of RSVPreF3 in adults aged 50–59 years \nHumoral immune response* at day 31 after a single d ose of RSVPreF3 in adults 60 and \nolder compared to: \n–Adults 50–59, healthy (without prespecified conditions associated with increased risk of severe \nRSV disease) OR \n–Adults 50–59, at-increased-risk (AIR, with conditions associated with increased risk of severe RSV \ndisease) \n•AIR conditions included: COPD resulting in activity  restricting symptoms or use of long-term \nmedication, chronic cardiovascular disease, diabete s mellitus type 1 or 2, chronic kidney disease, \nand chronic liver disease \nCellular immune response appeared similar across gr oups, but was not statistically \nevaluated \nSafety profile of RSVPreF3 in adults 50–59 years si milar to profile in 60 and older Today, GSK shared data demonstrating that the humoral i mmune \nresponse to a single dose of RSVPreF3 in adults 50– 59 years is non-\ninferior to that in adults 60 and older. \n*The primary immunogenicity analysis of non-inferio rity of the healthy and at-increased risk (AIR) 50– 59 year-old group versus the established vaccine ag e group of 60 and older \nwas based on geometric mean titer ratios and serore sponse rates. Data provided by GSK. 11 \n12 What do these new data mean for future policy? \nThe non-inferiority data suggest that RSVPreF3 vacc ine efficacy in \n(immunocompetent) adults aged 50–59 years with and without chronic medical \nconditions that increase risk of RSV disease will b e similar to efficacy \ndemonstrated among adults 60 years and older. \nThe Work Group notes that if FDA licensure is granted for use of RSVPreF3 in \nadults aged 50–59 years , then ACIP will likely need to make a policy \nrecommendation on: \n–Whether RSV vaccination should be recommended in th is age group? \n–And if so, should the recommendation be the same as in adults aged 60 years and \nolder, i.e. shared clinical decision-making, or is a  different type of recommendation \npreferred? \n13 Additional work group interpretations of immunogeni city data \nin adults aged 50–59 years \n Persons with immunocompromising conditions were exc luded from this trial (and \nprior trials). This is a group likely to benefit fr om RSV vaccination across the age-\nspectrum. \n Would have preferred efficacy data in this age grou p, noting that there is no \nimmunologic correlate of protection against RSV dis ease. \n If risk conditions are being prioritized, then thos e under 50 are also at risk and \nimmuno-bridging (and ideally efficacy) studies in a t-risk adults under 50 would \nalso provide important information. \nWork Group considerations on the use of RSV vaccines in adults aged 50–59 years \nRSV disease is a public health problem in adults ag ed 50–59 years. However, \nthe rate of RSV-associated disease in the general p opulation of adults 50–59 \nyears is less than the rate in adults 60 and older.\nAdjusted RSV-associated hospitalization rates* per 100,000 adults ≥18 years by 5-year age group and yea r, \nRSV-NET, 2015–2016 to 2019–2020 \n0100 200 300 400 500 600 \n18–49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 ≥85 Annual RSV-associated hospitalizations \nper 100,000 population 2015–16 2016–17 2017–18 2018–19 2019–20 \nRSV vaccination currently recommended, with SCDM \n26–59 \n23–42 \n*Unpublished data from RSV-NET. Rates are adjusted for the frequency of RSV testing during recent prio r seasons and the sensitivity of RSV diagnostic tes ts. 15 \nPersons with certain risk conditions are at increased risk of \nsevere RSV disease, even at younger ages. \n*Clinical data were collected for all patients with laboratory -confirmed RSV hospitalizations during the 2014–2015 to 2 017–2018 seasons, and for an age- and site-stratified r andom sample of patients with \nlaboratory-confirmed RSV hospitalizations during the 2022– 2023 season. Displayed percentages were weighted for th e probability of selection.\n†National Center for Health Statistics. United States, 202 2. National Health Interview Survey. Generated interactiv ely: Oct 17, 2023 from https://wwwn.cdc.gov/NHISDataQ ueryTool/SHS_adult/index.html Prevalence of certain medical conditions *among non-pregnant adults with RSV-associated hospi talizations (RSV-NET, 2014–2015 \nto 2017–2018 and 2022–2023) and among the general p opulation (National Center for Health Statistics †, 2022) by age group \n16 50–64 years ≥65 years \nGeneral \npopulation RSV-NET RSV-\nNET/ \nPop General \npopulation RSV-NET RSV-\nNET/ \nPop Condition % (95% CI) % (95% CI) % (95% CI) % (95% CI) \nCoronary artery disease 5.0 (4.4, 5.6) 18.9 (16.9, 21.0) 3.8 15.3 (14.4, 16.2) 31.3 (29.1, 33.6) 2.0 \nCOPD 6.2 (5.5, 6.9) 35.4 (32.9, 37.9) 5.7 9.8 (9.1, 10.5) 33.2 (30.1, 35.5) 3.4 \nDiabetes mellitus 13.8 (12.9, 14.7) 37.7 (35.1, 40.4) 2.7 20.1 (19.1, 21.1) 31.8 (29.6, 34.1) 1.6 \nAsthma 9.1 (8.4, 9.9) 28.6 (26.3, 31.0) 3.1 8.0 (7.3, 8.6) 17.6 (15.8, 19.4) 2.2 \nObesity 37.6 (36.2, 38.9) 46.4 (43.7, 49.0) 1.2 30.4 (29.2, 31.6) 28.4 (26.1, 30.8) 0.9 \nIn adults aged 50–59 years, hospitalization rates are higher among Black and \nAmerican Indian/Alaska Native adults than among White adults. There is an important equity component when considering the \nuse of RSV vaccine among adults aged 50–59 years. \n*Unpublished data from RSV-NET. Rates are adjusted for the frequency of RSV testing during recent prio r seasons and the sensitivity of RSV diagnostic tes ts. Black, White, \nAmerican Indian/Alaska Native and Asian/Pacific Isl ander people were categorized as non-Hispanic 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 \n18–49 50–59 60–64 65–74 ≥75 \nAsian or Pacific Islander White \nHispanic Black \nAmerican Indian or Alaska Native Burden-adjusted hospitalization rate ratios* among adults ≥18 years by \nrace and ethnicity — RSV-NET, 2016–2017 to 2019–2020\n17 \nWork Group is considering multiple policy options. \nUpcoming data on the implementation of shared clinica l decision-\nmaking, safety, and effectiveness (if available) wi ll be important to \ndetermine future preferred policy options, both among a dults 50–59 years \nand among those 60 and older. \nThe Work Group continues to believe that a focus on thos e at highest risk \nof severe RSV disease is warranted while awaiting pos t-marketing \nsurveillance data. Work Group preliminary considerations on the policy q uestion \n(part 1) \n18 \n19 Work Group preliminary considerations on the policy q uestion \n(part 2) \nWork Group members broadly agree that use of RSV va ccine among certain adults \naged 50–59 years is likely to have public health be nefit. \n–Members particularly acknowledge the equity concern  of a recommendation for this \nage group. \nIn addition, they note that if FDA licenses this pr oduct for adults 50–59 years, but \nthere is NO recommendation made, insurance will not  cover use in this age group, \npotentially furthering existing disparities. \nThe current priority of the Work Group is to ensure access to vaccination among \nadults 50–59 (and those ≥60) who are at substantial ly increased risk of severe \nRSV disease and likely to benefit most. \nRisk-based Risk-based Risk-based Risk-based Shared clinical \ndecision-making Shared clinical \ndecision-making Shared clinical \ndecision-making \nUniversal Universal \n50 55 60 65 70 75 80 85 90 Example 5 Example 4 Example 3 Example 2 Example 1 Current recommendation \nAge (years) Example potential policy options \n20 \n21 Next steps for the Work Group \nOver the next few months, the Work Group will review post-\nmarketing data on the use of RSV vaccines in adults 60 and older as \nthey become available, including: \n–Vaccine uptake , stratified by demographic characteristics and ris k conditions \n–Vaccine safety surveillance \nThe Work Group will consider the implementation and im plications of \nshared clinical decision-making \n22 Next steps for the Work Group \nThe Work Group will then develop an updated policy qu estion for RSV \nvaccination in adults through review of: \n–Updated GRADE of evidence profile for use of GSK’s RSVPreF3 in adults \n–Updated cost effectiveness analysis (CEA) of use of RSVPreF3 in adults \n–Updated Evidence to Recommendations framework for adult RSV \nvaccination \nThe Work Group will also begin reviewing safety and efficacy of a new \nRSV vaccine (Moderna’s mRNA-1345) for use in adults 60 and older \n1. What additional data are needed prior to ACIP votin g on updated recommendations \nfor RSV vaccination in adults aged ≥50 years? \n2. Other questions from ACIP? Questions for ACIP \n23 \nAdult RSV Work Group Membership \n24 ACIP Voting Members \nCamille Kotton (Chair) Keipp Talbot Sarah Long Ex Officio Members \nRachel Zhang (FDA) Judy Beeler (FDA) Nicholas Geagan (FDA) Nadine Peart Akindele (FDA) Sonnie Kim (NIH/NIAID) Jeffrey Kelman (CMS) Michelle Juaneza (HRSA/VICP) Uzo Chukwuma (IHS) Valerie Marshal (OIDP) Consultants \nRobert Atmar (Baylor Coll. of Medicine) Helen Chu (U Washington) Peter Donofrio (Vanderbilt University) Marie Griffin (Vanderbilt University) Cynthia Lucero-Obusan (VHA) Tracy Ruckwardt (NIH/NIAID) Jonathan Temte (U Wisconsin) Rebecca Morgan (Case Western) Doug Campos-Outcalt (U Arizona) \nLiaisons \nKenneth Schmader (AGS) Vidya Sundareshan (ACP) Gretchen LaSalle (AAFP) April Killikelly (NACI/PHAC) Winnie Su (NACI/PHAC) Katherine Williams (APTR) Ruth Lynfield (NFID) Bindy Crouch (AIM) Steven Pergam (IDSA) Elizabeth Skoy (APhA)\nCDC Contributors \nMichael Melgar (co-lead) Lauren Roper Fiona Havers Elisha Hall  Chris Taylor Monica Patton Meredith McMorrow Diya Surie Jennifer DeCuir Mila Prill Monica Godfrey Ruth Link-Gelles Amanda Payne Danielle Moulia Megan Wallace Natalie Thornburg Melissa Coughlin Jefferson Jones Katherine Fleming-Dutra Ismael Ortega Sanchez Noelle Molinari Pragna Patel Aron Hall Hannah Rosenblum Derrell Powers Raigan Wheeler Jarrett Gartin Elizabeth Greene Manisha Patel Lisa Grohskopf Anne Hause David Shay Christine Olson Tom Shimabukuro Karen Broder Neil Murthy Patricia Wodi Andrew Leidner Jamison Pike Sarah Meyer Nicole Dowling \n25 \nFor more information, contact CDC 1-800-CDC-INFO (232-4636) TTY:  1-888-232-6348    www.cdc.gov \nThe findings and conclusions in this report are tho se of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Pre vention. \nPhotographs and images included in this presentatio n are licensed solely for CDC/NCIRD online and pres entation \nuse. No rights are implied or extended for use in p rinting or any use by other CDC CIOs or any externa l audiences.", "summary": "Centers for Disease Control and Prevention  National Center for Immunization and Respiratory Di seases  Photographs and images included in this presentation a re licensed solely for CDC/NCIRD online and present ation  use. No rights are implied or extended for use in pr inting or any use by other CDC CIOs or any external audiences.  ACIP Adult RSV Work Group Considerations  Respiratory Syncytial Virus (RSV) in Adults Use of RSV vaccines in adults aged 50–59 years  Amadea Britton, MD, MS…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-25-26-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-10-25-26/04-Britton-Adult-RSV-508.pdf", "doc_date": "2023-10-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 26}
{"title": "01 influenza Loehr 508", "content": "National Center for Immunization & Respiratory Diseases\nInfluenza Work Group —Introduction\nDr. Jamie Loehr (Work Group Chair)\nAdvisory Committee on Immunization Practices\nOctober 25, 2023\nInfluenza Work Group\nACIP Members\n•Jamie Loehr (Chair)\n•Keipp Talbot \n•Camille Kotton\nEx Officio\n•Timothy Brennan (FDA)\n•Uzo Chukwuma (IHS)\n•Jeffrey Kelman (CMS)\n•Valerie Marshall (OASH)\n•Cynthia Nolletti (FDA)\n•Chris Roberts (NIH)Liaison Representatives and Consultants\n•Robert Atmar\n•Kevin Ault\n•Ed Belongia\n•Hank Bernstein\n•Thomas Boyce\n•Kris Bryant\n•Doug Campos -Outcalt\n•Sarah Coles\n•Frances Ferguson\n•Alicia Fry\n•Sandra Fryhofer\n•Wendy Keitel\n•Marie -Michèle Léger\n•Susan Lett\n•Krissy Moehling•Zackary Moore\n•Rebecca Morgan\n•Kathy Neuzil\n•Jesse Papenburg\n•William Schaffner\n•Rob Schechter \n•Ken Schmader \n•Tamara Sheffield\n•Angela Sinilaite\n•Patsy Stinchfield \n•Peter Szilagyi\n•Matthew Zahn\nCDC Lead\n•Lisa Grohskopf\n2\nCDC Participants\n•Lenee Blanton\n•Karen Broder\n•Alicia Budd\n•Jessie Chung\n•Sascha Ellington\n•Jill Ferdinands\n•Brendan Flannery\n•Andrew Kroger\n•Samantha Olson\n•David Shay\n•Tom Shimabukuro\n•Mark Tenforde\n•Tim Uyeki\n3\nInfluenza Vaccines in Pregnancy\nUpdates:\n• Safety of Quadrivalent Recombinant Influenza Vaccine in Pregnant Women and their Infants —\nDr. Nicky Klein (Kaiser Permanente Northern California)\n• Pregnancy Outcomes with ccIIV4 (Flucelvax); Post Marketing Study —Dr. Gregg Sylvester (Seqirus)\n• Effectiveness of Maternal Influenza Vaccination during Pregnancy Against Influenza -associated \nHospitalizations & ED Visits in Infants <6 Months of Age— Ms. Samantha Olson (CDC/NCIRD)       \n⁻ To be presented tomorrowIssues:\n• Influenza vaccination recommended for pregnant persons\n• While there is considerable experience with safe administration of influenza vaccines in \npregnancy, there are fewer data specific to newer influenza vaccine formulations\n4\nCo-administration of Vaccines in Adults\nUpdates:\n• Safety of Simultaneous versus Sequential Administration of mRNA COVID -19 and Quadrivalent \nInactivated Influenza (IIV4) Vaccines —Dr. Emmanuel “Chip” Walter (Duke University)\n• Safety of Simultaneous Vaccination with Zoster Vaccine Recombinant (RZV) and Quadrivalent \nAdjuvanted Inactivated Influenza Vaccine (allV4) —Dr. Kenneth Schmader (Duke University)\n• Update on COVID -19 and Influenza Vaccine Safety —Dr. Tom Shimabukuro (CDC/NCIRD)Issues:\n• Simultaneous administration or co -administration of all vaccines for which a recipient is due is a \ngenerally recommended practice for most combinations of vaccines\n• Specific data for co -administration of many combinations involving newer vaccines are limited\n• Data on co -administration of two or more vaccines with newer adjuvants are limited\n5\nInfluenza B/Yamagata Surveillance\nUpdate:\n• Update on Influenza B/Yamagata Surveillance— Dr. Rebecca Kondor (CDC/NCIRD) \n⁻ To be presented tomorrowIssues:\n• All current U.S. influenza vaccines are quadrivalent —they contain antigen from 4 influenza \nviruses, including an A(H1N1) virus, an A(H3N2) virus, and  2 influenza B viruses (one from each \nof two B lineages)\n• Quadrivalent influenza vaccines were initially introduced in 2013- 14, to permit broader coverage \nof potentially circulating influenza B viruses (previous trivalent vaccines contained one influenza \nB virus from one lineage)\n• There have been noconfirmed detections ofinfluenza B/Yamagata lineage viruses in global \nsurveillance since March 2020, leading to discussion by WHO and FDA of their continued \ninclusion in influenza vaccines\n6\nFor more information, contact CDC\n1-800- CDC- INFO (232- 4636)\nTTY:  1 -888- 232- 6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.", "summary": "National Center for Immunization & Respiratory Diseases Influenza Work Group —Introduction Dr. Jamie Loehr (Work Group Chair) Advisory Committee on Immunization Practices October 25, 2023 Influenza Work Group ACIP Members •Jamie Loehr (Chair) •Keipp Talbot  •Camille Kotton Ex Officio •Timothy Brennan (FDA) •Uzo Chukwuma (IHS) •Jeffrey Kelman (CMS) •Valerie Marshall (OASH) •Cynthia Nolletti (FDA) •Chris Roberts (NIH)Liaison Representatives and Consultants •Robert Atmar •Kevin Ault •Ed Belongia…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-25-26-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-10-25-26/01-influenza-Loehr-508.pdf", "doc_date": "2023-10-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 7}
{"title": "02 influenza klein 508", "content": "Safety of quadrivalent recombinant influenza \nvaccine in pregnant women and their infants\nNicky Klein, MD, PhD\nDirector, Kaiser Permanente Vaccine Study Center\nKaiser Permanente Northern California\nAdvisory Committee on Immunization Practices Meeting\nOctober 25, 2023\n\nDisclosures\n•Sanofi provide related research support for 'Flublok v. \nStandard Dose Vaccine Effectiveness Among Kaiser Permanente Northern California Adults 18- 64 Years' \n(NCT03694392).\n•Sanofi provided all the recombinant influenza vaccine for this study (1.2 million doses).\n•Unrelated research support from Pfizer, Merck, GSK and Seqirus.\n2\nBackground\n•Since 2004, the US Advisory Committee on Immunization \nPractices (ACIP) has recommended that all pregnant women receive an inactivated influenza vaccine during any trimester of pregnancy.\n̶includes recombinant influenza vaccine (RIV), which has been \navailable since 2013\n•There has been limited data regarding the safety of RIV during \npregnancy.\n•We conducted a post -licensure observational study to assess the \nsafety of RIV4 during pregnancy.\n3\nStudy Setting:\nKaiser Permanente Northern California (KPNC)\n•Integrated Healthcare Delivery System\n•Annual membership of >4 million (~65% aged 18– 64 years).\n•Members receive nearly all their care at KPNC facilities (259 \nmedical clinics, 21 hospitals).\n•KPNC has an electronic medical record (EMR) that captures all healthcare encounters, diagnoses, lab tests, \nvaccines, and medications.\n•Within KPNC, routine influenza PCR testing begins in early fall. Flu PCR tests are ordered at physician’s discretion.\n4\nStudy Objective\n•Primary objective: Evaluate the safety of quadrivalent \nrecombinant influenza vaccine compared with \nquadrivalent inactivated influenza vaccines in pregnant \nwomen and their offspring\n5\nPreliminary data\nStudy Design\n•Study included all routinely influenza- vaccinated pregnant women \nand their live born infants at Kaiser Permanente Northern \nCalifornia (KPNC) during the 2018- 2019 and 2019- 2020 influenza \nseasons.\n•All vaccinated pregnant women were a subset of a separate, cluster randomized effectiveness trial which compared the relative vaccine effectiveness (rVE) of RIV4 vs. SD -IIV4 against influenza \nand influenza- related outcome. \n6\nPreliminary data\n•Cluster randomized observational study of all KPNC adults vaccinated \nwith either RIV4 or SD -IIV4 during 2018- 2021 influenza seasons.\n•KPNC aimed to administer 400,000 RIV4 doses and 400,000 SD -IIV4 \ndoses to adults 18– 64 years during each of the 3 seasons.\n•To minimize geographic and socioeconomic imbalances between facilities and achieve balance in covariates, we cluster -randomized facilities within \neach of 7 service areas to receive RIV4 or SD -IIV4 on an alternating \nweekly basis.\n̶Randomization accounted for facility size, facilities within each service areas\n̶Goal was to achieve balance in covariate distribution between those who received \nRIV4 vs. SD -IIV4 (e.g., similar proportion of RIV4 vs. SD -IIV4 who were female)\n7Larger Relative Vaccine Effectiveness Study \nContext\nPreliminary data\n866 KPNC \nfacilities across \n7 geographic \nregionsRandomized within \ngeographic regions to \nBlock A or Block BBlock A\nBlock BWeek 1 Week 2 Week 3 Week 4\nFacility 1 RIV4 SD-IIV4 RIV4 SD-IIV4\nFacility 2 SD-IIV4 RIV4 SD-IIV4 RIV4\nFacility 3 SD-IIV4 RIV4 SD-IIV4 RIV4\nFacility 4 RIV4 SD-IIV4 RIV4 SD-IIV4\nFacility 5 SD-IIV4 RIV4 SD-IIV4 RIV4\nFacility 6 RIV4 SD-IIV4 RIV4 SD-IIV4Block A randomized \nassigned (coin toss) to \nuse RIV4 for Week 1Design of RIV4 and SD-IIV4 Relative Vaccine \nEffectiveness Study\n•Overall RIV4 vs SD- IIV4 rVE study included ~1.6 million influenza- vaccinated \nadults 18- 64 yrs\n•Study ultimately only included 2 seasons (2018- 2020) due to the COVID -19 pandemic\n•Current study focused on the subset of vaccinated pregnant women and their \noffspring from this overall rVE study\nPreliminary data\nStudy Outcomes\n9Pregnancy •Spontaneous abortion\n•Preterm labor\n•Stillbirth/fetal death\n•Congenital/fetal anomalies detected during pregnancy\n•Eclampsia\n•Placental abruption\nBirth •Preterm birth\n•Low birthweight\n•Small for gestational age\nNeonatal/Infant \n(through 365 days)•Infant death\n•Congenital anomalies \n•Failure to thrive\nPreliminary data\nStatistical Analysis\nPregnancy outcomes: \n•Compared the odds of a pregnancy outcome among RIV4 vaccinated \npregnant women with SD- IIV4 vaccinated pregnant women.\n̶Conditional logistic regression ( conditioned on gestational age)\n̶Adjusted for maternal race, ethnicity, age group, BMI, presence of any chronic \ncondition (asthma, CHD, COPD, diabetes), and trimester of influenza vaccination\nBirth and neonatal/infant outcomes: \n•Compared the odds of birth and neonatal outcomes among RIV4 \nvaccinated pregnant women with SD -IIV4 vaccinated pregnant women.\n̶Logistic regression\n̶Adjusted for infant sex, race, ethnicity, maternal age group, and maternal trimester \nof influenza vaccination\n10\nPreliminary data\nFinal Population: Flu Vaccinated Pregnant Women and their Infants\n11Pregnant women vaccinated at KPNC\n2018-2019 & 2019-2020 influenza seasons\nN=54,360\nRIV4 vaccinated\nn=16,609SD-IIV4 vaccinated\nn=37,751\nExcluded*\nn=1,628\nRIV4 -vaccinated\nPregnant Women\nn=14,981SD-IIV4-vaccinated \nPregnant Women\nn=33,800\nRIV4: Quadrivalent recombinant influenza vaccine ( Flublok Quadrivalent)\nSD-IIV4: Quadrivalent standard- dose inactivated influenza vaccine (Fluarix Quadrivalent or Flulaval Quadrivalent)\n*Excludes individuals who received ≥1 influenza vaccination in the same day and in the same season; data discrepancies such as missing sex, males identified as pregnant, date of death occurring \nbefore date of birth, etc.; not a KPNC member at time of vaccination; vaccinated in inpatient setting; or did not have a prenatal visit during pregnancyRIV4 Infant Cohort\nn=14,538SD-IIV4 Infant Cohort\nn=32,856Excluded*\nn= 3,951\nPreliminary data\nDemographics: Pregnant Women\n12RIV4\nN=14,981 (%)SD-IIV4\nN=33,800 (%)\nMaternal age* 17-24 years 1,544 (10.3) 3711 (11.0)\n24-35 years 9,586 (64.0) 21,297 (63.0)\n35-44 years 3,812 (25.4) 8680 (25.7)\n≥45 years 39 (0.3) 112 (0.3)\nTrimester of \nvaccination28 days prior to conception 750 (5.0) 1,367 (4.0)\n1sttrimester 5,092 (34.0) 10,787 (31.9)\n2ndtrimester 4,851 (32.4) 11,470 (33.9)\n3rdtrimester 4,288 (28.6) 10,176 (30.1)\nRace Asian 4,620 (30.8) 9,916 (29.3)\nBlack 620 (4.1) 1,589 (4.7)\nMultiracial 744 (5.0) 1,678 (5.0)\nNative American 46 (0.3) 102 (0.3)\nPacific Islander 153 (1.0) 287 (0.3)\nWhite 5,506 (36.8) 11,666 (34.5)\nUnknown 3,292 (22.0) 8,562 (25.3)\nHispanic Hispanic 3,450 (23.0) 8,898 (26.3)\nNon-Hispanic 11,531 (77.0) 24,902 (73.7)\nComorbidity † Asthma, CHD, COPD, or diabetes 2,036 (13.6) 4,779 (14.1)\n*All subjects were 18 years of age at the time of immunization; †Asthma, CHD, COPD, or diabetes assessed during the 3 years p rior to vaccinationPreliminary data\n13Outcome RIV4\nN=14,981 \nn (%)SD-IIV4\nN=33,800 \nn (%)Adjusted OR \n(95% CI)*P-\nvalue\nSpontaneous abortion 470 (3.1) 1,013 (3.0) 0.95 (0.85, 1.05) 0.31\nPreterm labor 546 (3.6) 1,170 (3.5) 1.06 (0.99, 1.14) 0.09\nStillbirth/fetal death 63 (0.4) 153 (0.5) 0.84 (0.68, 1.04) 0.12\nCongenital/fetal anomalies \ndetected during pregnancy356 (2.4) 798 (2.4) 1.00 (0.91, 1.09) 0.96\nEclampsia/pre- eclampsia 1,235 (8.4) 2,793 (8.4) 1.01 (0.96, 1.06) 0.64\nPlacental abruption 115 (0.8) 237 (0.7) 1.12 (0.96, 1.31) 0.15\n*SD-IIV4 was the reference group for all analyses. Conditional logistic regressions adjusted for maternal race, ethnicity, \nmaternal age group, trimester of influenza vaccine receive, chronic conditions, and BMIResults: Pregnancy Outcomes\nPreliminary data\nInfant Demographics\n14RIV4\nN=14,538 (%)SD-IIV4\nN=32,856 (%)\nSex Male 7,437 (51.2) 16,940 (51.6)\nFemale 7,101 (48.8) 15,916 (48.4)\nRace Asian 3,863 (26.6) 8,300 (25.3)\nBlack 496 (3.4) 1,257 (3.8)\nMultiracial 949 (6.5) 1,949 (5.9)\nNative American 20 (0.1) 66 (0.2)\nPacific Islander 128 (0.9) 298 (0.9)\nWhite 4,690 (32.3) 9,880 (30.1)\nUnknown 4,392 (30.2) 11,106 (33.8)\nHispanic Hispanic 3,059 (21.0) 7,857 (23.5)\nNon- Hispanic 11,479 (79.0) 24,999 (76.1)\nGestational Age Preterm (<37 weeks) 1,061 (7.3) 2,450 (7.5)\nPreliminary data\nResults: Birth/Infant Outcomes\n15*SD-IIV4 was the reference group for all analyses. Logistic regressions adjusted for infant sex, infant race, infant \nethnicity, maternal age group, and maternal trimester of influenza vaccine receiptOutcomeRIV4\nN=14,538\nn (%)SD-IIV4\nN=32,856\nn (%)Adjusted OR \n(95% CI)*P-value\nBirth\nPreterm birth 1,061 (7.3) 2,450 (7.5) 0.98 (0.91, 1.05) 0.54\nLow birth weight 852 (5.9) 1,918 (5.8) 1.00 (0.92, 1.09) 0.92\nSmall for gestational age 1,277 (8.8) 2,846 (8.7) 1.01 (0.94, 1.09) 0.72\nInfant (up to 365 days)Infant death 27 (0.2) 59 (0.2) 1.05 (0.66, 1.65) 0.85\nCongenital anomalies 6,259 (43.1) 14,018 (42.7) 1.01 (0.97, 1.05) 0.53\nMajor congenital anomalies 1,113 (7.7) 2,531 (7.7) N/A N/A\nMinor congenital anomalies 5,698 (39.2) 12,762 (38.8) N/A N/A\nFailure to thrive 150 (1.0) 372 (1.1) 0.90 (0.75, 1.09) 0.29\nPreliminary data\nStudy Strengths\n16•All pregnant women in this study were a subset of a large \nmodified cluster- randomized rVEstudy of RIV4 vs. SD -IIV4 (~1.6 \nmillion adults).\n̶RIV4 recipients were very similar to SD -IIV4 recipients with respect to \nrisk factors for adverse outcomes.\n̶Fewer sources of bias than in most observational studies.\nPreliminary data\nStudy Limitations\n17•There were slight imbalances in the timing of vaccination that may \nhave been related to provider preferences.\n̶The proportion of pregnant women who received RIV4 during preconception or first \ntrimester was relatively higher than in the SD -IIV4 group.\n̶Historically, the KPNC OB/GYN clinics have been accustomed to using SD -IIV4 in \npregnant woman.\n̶It is possible that providers preferred to administer SD -IIV4 once they knew an individual \nwas pregnant.\n•However, since demographic and covariate factors were similar \nbetween the two groups, such slight imbalances were unlikely to have \naffected the analyses.\nPreliminary data\nSummary\n18•Within a large population of influenza- vaccinated pregnant women, \ncomparing RIV4 with SD -IIV4 there were no differences in pregnancy, \nbirth and neonatal/infant outcomes.\n•No safety concerns were identified after RIV4 use in pregnancy.\n•The proportion of pregnancies or live births with outcomes was lower \nthan published US rates from most other studies.\n•This study provides reassuring safety evidence regarding the continued use of influenza vaccines in pregnant women.\nPreliminary data\nAcknowledgments\n19Amber Hsiao\nArnold YeeBruce FiremanJohn HansenNed Lewis\nNicola KleinSonja Banga\nAlexandre Selmani\nOxana TalanovaAjinkya Inamdar\n*\nLynn SchultzBarbara CourssarisKimberly HarpPenny PostHeidi KablerMaria Martin\n‡\nRuvim Izikson\n*BioNTech -Cambridge, Massachusetts (United States)\n‡Moderna -Cambridge, Massachusetts (United States)", "summary": "Safety of quadrivalent recombinant influenza  vaccine in pregnant women and their infants Nicky Klein, MD, PhD Director, Kaiser Permanente Vaccine Study Center Kaiser Permanente Northern California Advisory Committee on Immunization Practices Meeting October 25, 2023  Disclosures •Sanofi provide related research support for 'Flublok v.  Standard Dose Vaccine Effectiveness Among Kaiser Permanente Northern California Adults 18- 64 Years'  (NCT03694392). •Sanofi provided all the recombinant…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-25-26-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-10-25-26/02-influenza-klein-508.pdf", "doc_date": "2023-10-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 19}
{"title": "03 influenza sylvester", "content": "Gregg C. Sylvester, MD, MPH\nACIP Meeting Pregnancy Outcomes with ccIIV4 \n(Flucelvax); Post Marketing Study\nOctober 25, 2023\n2Study Overview\nPurpose Post -marketing commitment\nMain Objective Evaluate specific pregnancy and fetus/infant outcomes\nStudy Design Prospective, observational safety study\nStudy Population Patients immunized with ccIIV4 as part of routine obstetrical care\nScientific \nOversight \nCommitteeTeratologist, blinded to exposure timing, reviewed and classified \nreported malformations using the MACDP criteria\nIndependent experts in maternal -fetal medicine, pediatrics, \nclinical research, infectious disease, epidemiology, and teratology \nreviewed safety data and aligned on malformation classification(s)\nMACDP, Metropolitan Atlanta Congenital Defects Program; OB/GYN, ccIIV4 , cell -based quadrivalent influenza vaccine (Flucelvax)\n3Outcomes\nPregnancy Outcomes\n•Live birth\n•Stillbirth:\n•Fetal death occurring ≥20 weeks’ \ngestation, or if gestational age was \nunknown, a fetus that weighed 500 gm \nor more\n•Spontaneous abortion:\n•Fetal death <20 weeks’ gestation, \nincluding missed abortion, incomplete \nabortion, and inevitable abortion\n•Elective termination\n•Voluntary interruption of pregnancy, \nincluding pregnancy termination that \noccurred electively, to preserve \nmaternal health, or due to fetal \nabnormalitiesEvents of Interest\n•Preterm birth :\n•A live -born infant born at gestational \nage <37 weeks\n•Low birth weight :\n•A live -born infant whose birth weight is \n<2500 gm\n•Major Congenital Malformation:\n•Any major structural or chromosomal \ndefect or combination of three or more \nconditional defects in live -or stillborn \ninfants, or fetal losses of any \ngestational age, including outcomes \nprior to 20 weeks’ gestation or \nweighing <500 gm\n4Eligibility/Ineligibility Criteria\nEligible Cases:\n•Pregnant patients were enrolled prospectively \n•Sufficient information to confirm that vaccination with ccIIV4 \noccurred during routine obstetrical care \n•HCP’s contact information to allow for follow -up\n•Subjects may have self -enrolled or may have been enrolled by a \nparticipating OB/GYN clinic after providing informed consent\nIneligible Cases: \n•Retrospective cases\n•Persons who had prior knowledge of an adverse pregnancy \noutcome\nHCP -healthcare professional; OB/GYN -obstetrics and gynecology; ccIIV4 -cell-based quadrivalent influenza vaccine.\n5Study Enrollment Over Three US Influenza Seasons\nPersons Enrolled\n2017/2018 10 \n2018/2019 268\n2019/2020 415\nTotal Enrolled 693\nLost to Follow -up (27)\nIneligible (1)\nPrimary Analysis Population 665\n6Demographics\nPrimary analysis population (PAP)\nMaternal age at conception (years) N=665 \nMean (SD) 28.0 (5.3)\nMedian 28.0\nMin, max 17, 45\nPaternal age at enrollment (years) N=612\nMean (SD) 30.4 (6.2)\nMedian 30.0\nMin, max 17, 59\nEthnicity n (%) N=665\nHispanic or Latino 44 (6.6%)\nNot Hispanic or Latino 437 (65.7%)\nMissing* 184 (27.7%)\nRace n (%) N=665\nWhite 399 (60.0%)\nBlack or African American 194 (29.2%)\nAsian 29 (4.4%)\nAmerican Indian or Alaskan Native 1 (0.2%)\nNative Hawaiian or Other Pacific Islander 2 (0.3%) \nOther 28 (4.2%)\nUnknown 12 (1.8%)\nSD, standard deviation *One clinic did not report ethnicity.\n7Baseline Characteristics\nPrimary analysis population (PAP)\nPre-Pregnancy BMI (kg/m2) N=661\nMean (SD) 29.6 (8.2)\nMedian 28.1\nMin, max 15.0, 64.8\nNumber of previous pregnancies, n (%) N=665\n0 195 (29.3%)\n1 186 (28.0%)\n2 135 (20.3%)\n≥3 149 (22.4%)\nFamily history of congenital malformations, n (%) N=665\nOffspring 8 (1.2%)\nMaternal history 40 (6.0%)\nPaternal history 40 (6.0%)\nAny family history 78 (11.7%)\nAny concurrent condition, n (%) 527 (79.2%)\nAny concomitant medications, n (%) 651 (97.9%)\nSubstance use, n (%)\nAny tobacco use 84 (12.6%)\nAny alcohol use 1 (0.2%)\nAny illicit drug use N/A\nBMI, body mass index; N/A, not applicable; SD, standard deviation\n8Exposure by Gestational Age\n051015202530354045\n0 5 10 15 20 25 30 35 40 45Number of exposures\nGestational age at exposure (weeks)\nFirst trimester Second trimester Third trimesterNumber of patients by gestational age at exposure to ccIIV4 (in weeks)\nAmong all subjects identified (N=693)\nccIIV4 , cell -based quadrivalent influenza vaccine.\n9Results:  Pregnancy Outcomes\nOutcomeVaccine Exposure\nOverall\nFirst Trimester Second Trimester Third Trimester\nPrimary Analysis \nPopulationn=178 n= 277 n= 210 n=665\nLive Birth, n\n% (95% CI)172\n96.6% (92.8 -98.8)277\n100% (98.7 -100)210\n100% (98.3 -100)659\n99.1% (98.0 -99.7)\nStillbirth0\n0 (0.0-2.1)0\n0 (0.0-1.3)0\n0 (0.0-1.7)0\n0 (0.0-0.6)\nEnrollment <20 weeks         \ngestationn=147 n= 64 N/A n=211\nSpontaneous Abortion*4\n2.7% (0.7-6.8)0\n0 (0.0-5.6)N/A4\n1.9% (0.5-4.8)\nElective Termination*1\n0.7% (0.0-3.7)0\n0 (0.0-5.6)N/A1\n0.5% (0.0-2.6)\n*Calculated using the population enrolled at <20 weeks of gestation (n = 211) as the denominator.\n10Results:  Events of Interest\n10.2\n8.3\n2.89.2\n5.8\n1.9\n024681012\nPreterm birth Low birthweight Major Cong. MalformationsPercentage of events of interest (95% CI)US prevalence (%) Study prevalence (%)\nCDC, Centers for Disease Control and Prevention; CI, confidence interval; MACDP, Metropolitan Atlanta Congenital Defects \nProgram; MCM, major congenital malformation ; NCHS, National Center for Health Statistics; NVSS, National Vital Statistics System. \n1. Martin JA, et al. NCHS Data Brief. 2020;387:1 –8;2. Martin JA, et al. Natl Vital Stat Rep. 2019;68:1 –47; 3. Correa A, et al. Birth Defects \nRes A Clin Mol Teratol . 2007;79:65 –93.\n11Results: Major Congenital Malformations\nTiming of Vaccine/\nWeeks GAPreferred MACDP term Trimester of Vaccine\nFirst5.4 Sex chromosome –XYY \n10.7 Talipes equinovarusSecond16.1 Renal agenesis, right\n16.1 Polycystic kidneys *\n16.4Clubfoot, cardiomegaly, aorta malformation     \n(unknown), hypoplasia of upper or lower limb\n18.1 Situs inversus abdominus\n19.9 Hirschsprung’s Disease\n23.0 Fluid around kidneys \n24.9 Micropenis , microphthalmosThird30.3 Transposition of great vessels\n32.1Trisomy 21, atrial septal defect, patent ductus \narteriosus\n33.0 Absent foreskin\n33.3 Hypospadias\n33.4 Absent forearm\nGA –Gestational Age, MACDP -Metropolitan Atlanta Congenital Defects Program\n*One infant who died 24h after birth had polycystic kidneys and fetal anhydramnios reported during pregnancy. Key:\nDefect with known cause\nNo temporal association\nUnable to assess temporality \n12Strengths and Limitations\nStrengths\n•>660 Subject enrolled across \nmultiple influenza seasons\n•Diverse population which \nincluded racial and ethnic groups \nas well as a broad range of \nmaternal ages\n•Enrollment occurred at five study \nsites in four statesLimitations\n•Effect of potential confounders \n(previous pregnancy outcomes, \npregnancy complications, etc.) \n•Potential for missing data or \nlimited level of detail collected as \npart of routine care \n•MACDP counts MCMs detected \nup to the age of 6 years\nMACDP -Metropolitan Atlanta Congenital Defects Program, MCM –Major Congenital Malformations\n13Conclusion\n•The findings are consistent with published data from various \ndatabases and surveillance systems that monitor the safety of \ninfluenza vaccines1–5\n•The independent expert committee found no evidence of a safety \nconcern \n•These data support the use of ccIIV4 for immunization against \ninfluenza in this population\n1. Chambers CD, et al. Vaccine. 2016;34(37):4443 –4449; 2. Zerbo O, et al. Vaccine. 2017;35(24):3186 –3190; 3. Donahue JG, et al. \nVaccine. 2019;37(44):6673 –6681; 4. Moro P, et al. Drug Saf.2017;40(2):145 –152; 5. Louik C, et al. Vaccine. 2016;34(37):4450 -4459.", "summary": "Gregg C. Sylvester, MD, MPH ACIP Meeting Pregnancy Outcomes with ccIIV4  (Flucelvax); Post Marketing Study October 25, 2023 2Study Overview Purpose Post -marketing commitment Main Objective Evaluate specific pregnancy and fetus/infant outcomes Study Design Prospective, observational safety study Study Population Patients immunized with ccIIV4 as part of routine obstetrical care Scientific  Oversight  CommitteeTeratologist, blinded to exposure timing, reviewed and classified  reported…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-25-26-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-10-25-26/03-influenza-sylvester.pdf", "doc_date": "2023-10-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 13}
{"title": "04 Influenza Walter 508", "content": "Safety of Simultaneous versus Sequential \nAdministration of mRNA COVID -19 and\nQuadrivalent Inactivated Influenza (IIV4) \nVaccines: A Randomized Placebo Controlled Trial\n(ClinicalTrials.gov ID: NCT05028361)\nEmmanuel “Chip” Walter MD, MPH\nACIP October 25, 2023\nDisclaimer\n•The findings and conclusions in this presentation are \nthose of the presenter and do not necessarily represent the official position of the Centers for Disease Control and Prevention\n•Mention of a product or company name is for identification purposes only and does not constitute endorsement by CDC\n•This study was supported by the CDC Clinical Immunization Safety Assessment (CISA) Project \n2\nStudy Rationale\n•Influenza and COVID -19 vaccines are recommended \nfor persons 6 months of age and older to prevent \nillness and complications resulting from these infections.\n*\n•Available data support the simultaneous administration of these vaccines as currently ACIP recommended.\n•However, there are limited data from placebo-controlled studies (none from the US) evaluating the safety of simultaneous administration of influenza and mRNA COVID -19 vaccines.\n3*Clinical Guidance for COVID- 19 Vaccination | CDC and Prevention and Control of Seasonal Influenza with Vaccines: Recommendations \nof the Advisory Committee on Immunization Practices —United States, 2023– 24 Influenza Season | MMWR (cdc.gov)\nDesign, Population, Recruitment\n•Design : prospective, randomized, \nplacebo -controlled, observer -blind \nstudy\n•Population : non- pregnant persons aged \n≥5 years if receiving primary two -dose \nmRNA COVID -19 vaccine series or \npersons aged ≥12 years if receiving a \nbooster mRNA COVID -19 vaccine dose \nand intending to receive a quadrivalent \ninactivated influenza vaccine (IIV4)*\n•Recruitment : 3 CISA sites –Duke \nUniversity, Cincinnati Children’s Hospital Medical Center (CCHMC), and John Hopkins University (JHU) during \nthe 2021- 2022 and 2022- 2023 \ninfluenza seasons \n4\nSimultaneousSequentiala\n*Persons ≥65 years received High -Dose IIV4 (Fluzone High -Dose Quadrivalent); those <65 years received standard dose IIV4 (FluLaval or Fluzone Quadrivalent)   \nStudy Aims and Objectives: \nPrimary objective : To compare the proportion of participants with \nmoderate or more severe fever, chills, myalgia, or arthralgia (RE)* \nin the group receiving IIV4 simultaneously with mRNA COVID -19 \nvaccine at Vaccination Visit  1 (Simultaneous group) with the group receiving IIV4 alone one to two weeks later at Vaccination Visit 2 \n(Sequential group) following both Vaccination Visit 1 and 2\n–Primary outcome: considered present if participant has at least one of \nthe RE symptoms on at least one day during days 1 to 7 following Visit 1 and/or Visit 2   \nHypothesis :  The proportion of participants with moderate or more \nsevere fever, chills, myalgia or arthralgia will be non -inferior (not \nhigher) in the Simultaneous group versus the Sequential group\n5*RE: reactogenicity event \nSecondary Objectives\n•To compare the proportion of participants with RE in the \nSimultaneous group versus the Sequential group following Vaccination Visit 1 and 2 separately\n•To describe the proportions of participants in each group with solicited local and systemic reactogenicity events according to \nseverity grade after vaccination visits\n•To describe the proportions of participants in each group experiencing at least one serious adverse event and a description of these events\n6\nStudy Aims and Objectives: \nExploratory Objectives\n•To further characterize and describe the proportion of participants \nin each group with local or systemic reactogenicity events of \ngreater severity \n•To describe the proportion of participants each group experiencing at least one unsolicited adverse event and one adverse event of special interest and to characterize these events\n•To compare the change of health -related quality of life (HRQOL) \nfrom baseline in both groups following the Vaccination Visit 1 \n7\nStudy Procedures Summary\n•After randomization (1:1) to either the simultaneous or \nsequential group and a baseline blood draw, participants \nreceived study influenza vaccine or placebo according to \nassignment \n•Solicited Reactogenicity: Days 1 -7* after V1, V2, V3a \n•Unsolicited Adverse Events: Days 1 -7 after V1, V2, V3a \n•Health -Related Quality of Life (HRQOL): Days 1 -7 after V1 \nonly\n•Adverse Events of Special Interest (AESIs): Days 1 -121 \n•Serious Adverse Events (SAEs): Days 1 -121\n•Blood draws for immunogenicity: baseline and post -\nvaccination (data not yet available)    \n8 *Day 1 is the vaccination day  \nStatistical Methods\n•Full Analysis Population 2\n–All randomized and vaccinated participants\n–Participant characteristics and adverse event outcomes\n•Full Analysis Population 1\n–All participants who are randomized, vaccinated, and provide at least one day of complete data on the \nsymptom diary\n–Reactogenicity outcomes\n•Statistical Testing\n–Primary outcome was conducted at the one -sided alpha 0.025 level using the upper bound of a stratified by site \nNewcombe binomial confidence interval with Cochran -Mantel -Haenszel (CMH) weighting of the difference with \na noninferiority margin of 10%.  \n–Comparisons of proportions between the simultaneous and sequential groups used an exact Mantel -Haenszel \nstatistic in a stratified analysis by site to control for the randomization blocks at the two- sided alpha 0.05 level.  \nStudy site adjusted odds ratios and corresponding 95% confidence intervals for proportions were also calculated. \n–The changes in HRQOL after Visit 1 were evaluated using Mann -Whitney U tests. For the HRQOL comparisons \nwe used a two- sided alpha at the 0.05 level. \n–Summary statistics were used to describe REs, AEs, SAEs and AESIs.  95% confidence intervals of the difference between vaccination groups were calculated.\n9\nStudy Consort Diagram\n10\n\nDemographics / Enrollment Site\nCharacteristic Simultaneous (n=169) Sequential (n=166) Total (N=335)\nSex:             Female 96 (56.8%) 115 (69.3%) 211 (63.0%)\nMale 73 (43.2%) 51 (30.7%) 124 (37.0%)\nRace:          White Only 123 (72.8%) 113 (68.1%) 236  (70.4%)\nBlack Only 31 (18.3%) 33(19.9%) 64 (19.1%)   \nOther 15 (8.9%) 20 (12.0%) 35 (10.4%)\nEthnicity: Hispanic 12 (7.1%) 9 (5.4%) 21 (6.3%)\nAge (yrs):   5 to <12 4 (2.4%) 2 (1.2%) 6 (1.8%)\n12 to <18 11 (6.5%) 13 (7.8%) 24 (7.2%)\n18to <65 146 (86.4%) 143 (86.1%) 289 (86.3%)\n>=65 8 (4.7%) 8 (4.8%) 16 (4.8%)\nSite:           CCHMC 67 (39.6%) 63 (38.0%) 130 (38.8%)\nDuke 79 (46.7%) 81 (48.8%) 160 (47.8%)\nJHU 23 (13.6%) 22 (13.3%) 45 (13.4%)\n11\nSeason, COVID -19 Vaccine Received, \nVaccination and COVID -19 History\nCharacteristic Simultaneous (n=169) Sequential (n=166) Total (N=335)\nSeason:     2021- 2022 37 (21.9%) 36 (21.7%) 73 (21.8%)\n2022- 2023 132 (78.1%) 130 (78.3%) 262 (78.2%)\nCOVID -19 Vaccine Brand:\nPfizer -BioNTech Monovalent 34 (20.1%) 35(21.1%) 69(20.6%)\nPfizer -BioNTech Bivalent 130 (76.9%) 125 (75.3%) 255 (76.1%)\nModerna  Monovalent 4   (2.4%) 4 (2.4%) 8 (2.4%)\nModerna Bivalent 1   (0.6%) 2 (1.2%) 3 (0.9%)\nPrior COVID -19 Vaccine\nYes 165 (97.6%) 166 (100.0%) 331 (98.8%)\nPrior COVID -19 and/or \n+ nucleocapsid ab  \nYes 96 (56.8%) 95 (57.2%) 191 (57.0%)\n12\nPrimary Outcome \nProportions with moderate or more severe fever, chills, myalgia, or arthralgia \n(RE) in participants in sequential versus simultaneous group \n13Moderate or more severe fever, chills, myalgia,  or arthralgia following Visit 1 and/or Visit 2\nNo Yes Non -inferiority Test 10% Margin*\nGroup N % N % Diff Lower \n95% CIUpper \n95% CIp-value\nSimultaneous 125 74.40 43 25.60\nSequential 114 68.67 52 31.33 -0.0563 -0.1517 0.0404 0.0007\nHo: Sim-Seq≥ 0.10 (10%)\nConclusion: The rate of moderate or more server fever, chills, myalgia, or \narthralgia in simultaneous group is considered not worse/not higher than \nthe rate in sequential group and the noninferiority criteria was met. The \nupper limit of the 95% confidence interval (CI) of the difference for Sim \nminus Seq was 4.0% and the noninferiority margin was 10%; therefore, the \nnull hypothesis of inferiority was rejected . *Site -stratified Newcombe binomial confidence interval with Cochran -Mantel -Haenszel (CMH) weighting of the difference \nObjective :  To compare the proportion of participants with \nmoderate or more severe fever, chills, myalgia, or arthralgia in the \nSimultaneous versus the Sequential Group following the first \nvaccination visitSecondary Objective\n14Moderate or more severe fever, chills, myalgia,  or arthralgia following Visit 1 \nNo Yes\nGroup N % N % Odds Ratio (95%CI) p-value*\nSimultaneous 128 76.19 40 23.81\nSequential 119 71.69 47 28.31 0.80 (0.49, 1.30) 0.3851\n*Exact Mantel -Haenszel statistic in a stratified analysis by site \nObjective :  To compare the proportion of participants with \nmoderate or more severe fever, chills, myalgia, or arthralgia in the \nSimultaneous versus the Sequential Group following the second \nvaccination visitSecondary Objective\n15Moderate or more severe fever, chills, myalgia,  or arthralgia following Visit 2 \nNo Yes\nGroup N % N % Odds Ratio (95%CI) p-value*\nSimultaneous 163 97.02 5 2.98\nSequential 157 94.58 9 5.42 0.54 (0.18, 1.63) 0.2886\n*Exact Mantel -Haenszel statistic in a stratified analysis by site \nPercent With Injection Site Reaction \nVisit 1\n16More ≥ moderate pain in simultaneous group* More ≥ moderate pain and swelling in sequential group*\n*95% CI of difference in proportions between  does not contain zero020406080100\n Sim Seq Sim Seq Sim Seq Sim Seq\nPain Swelling Erythema Axillary Swelling\nand TendernessPercent\nSolicited Event and GroupInjection Site Reactions Visit 1\nCOVID -19 Vaccine\nMild Moderate Severe Life Threatening020406080100\nSim Seq Sim Seq Sim Seq Sim Seq\nPain* Swelling Erythema Axillary Swelling\nand Tenderness*Percent\nSolicited Event and GroupInjection Site Reactions Visit 1\nInfluenza Vaccine or Placebo\nMild Moderate Severe Life Threatening*95% CI of difference does not contain zero\n*95% CI of difference in proportions between  does not contain zero\n17Percent With Injection Site Reaction \nVisit 2\nMore ≥ moderate pain and axillary swelling/ tenderness in sequential group*\n*95% CI of difference in proportions between  does not contain zero020406080100\nSim Seq Sim Seq Sim Seq Sim Seq\nPain* Swelling* Erythema Axillary Swelling and\nTenderness*Percent\nSolicited Event and GroupInjection Site Reactions Visit 2\nInfluenza Vaccine or Placebo\nMild Moderate Severe Life Threatening*95% CI of difference does not contain zero\n18Percent With Systemic  Reaction \nVisit 1\nNo differences in ≥ moderate systemic symptoms020406080100\nSim Seq Sim Seq Sim Seq Sim Seq Sim Seq Sim Seq Sim Seq Sim Seq\nFever Chills Fatigue Myalgia Headache Arthralgia Nausea &\nVomitingDiarrheaPercent\nSolicited Event and GroupSystemic Reactions Visit 1\nMild Moderate Severe Life Threatening\n19Percent  With Systemic  Reaction \nVisit 2\nNo differences in ≥ moderate systemic symptoms020406080100\nSim Seq Sim Seq Sim Seq Sim Seq Sim Seq Sim Seq Sim Seq Sim Seq\nFever Chills* Fatigue* Myalgia* Headache Arthralgia Nausea &\nVomitingDiarrhea*Percent\nSolicited Event and GroupSystemic Reactions Visit 2\nMild Moderate Severe Life Threatening*95% CI of difference does not contain zero\nObjective : To describe the proportions of participants in the \nSimultaneous and Sequential vaccination groups experiencing at \nleast one serious adverse event and a description of these \neventsSecondary Objective\n20At  Least One Serious Adverse Event\nNo Yes\nGroup N % N % Difference (Sim -Seq)(95%CI)\nSimultaneous 168 99.41 1 0.59\nSequential 165 99.40 1 0.60 -0.01 ( -1.66, 1.64)\nSAE Descriptions\n21Group Vaccine Onset \nsince Visit \n1 Sex Age groupCategory Relatedness Description\nSequential Pfizer -BioNTech \nBivalent14 days Female 50-64 Hospitalization/\nprolongation of \nexisting hospitalizationUnlikely related Small bowl obstruction with \nincarcerated ventral herniaPast medical history (PMH): abdominal surgeries and cancer\nSimultaneous Pfizer -BioNTech  \nMonovalent19  Weeks Female 18-49 \nyears Other importantmedical eventNot related Spontaneous abortion occurring at \n16 weeks gestation PMH: COVID -19 illness (mild) 9 \nweeks after visit 1; (Note: Participant did not report being pregnant or intention of becoming pregnant at enrollment)​\n•Objective : To describe the proportion of participants in Simultaneous and \nSequential groups experiencing at least one unsolicited adverse event \nand one adverse event of special interest and to characterize these eventsExploratory Objective\n22At  Least One Unsolicited Adverse Event within 7 Days of a Vaccination Visit (Preliminary)\nNo Yes Percent Yes\nGroup N % N % 95% CI Difference (Sim -Seq)\n(95%CI)\nSimultaneous 148 87.57 21 12.43 (7.86, 18.37)\nSequential 150 90.36 16 9.64 (5.61, 15.18) 2.79 ( -3.91, 9.49)\n•AEs within 7 days of vaccine (n=45)\n–29 simultaneous group in 21 participants (3 possibly related)\n–16 sequential group in 16 participants (1 related, 2 possibly related)\n•Objective : To describe the proportion of participants in Simultaneous and \nSequential groups experiencing at least one unsolicited adverse event and one \nadverse event of special interest and to characterize these eventsExploratory Objective\n23At  Least One Adverse Event of Special Interest\nNo Yes Percent Yes\nGroup N % N % 95% CI Difference (Sim -Seq)\n(95%CI)\nSimultaneous 150 88.76 19 11.24 (6.91, 17.00)\nSequential 157 94.58 9 5.42 (2.51, 10.04) 5.82 ( -0.06, 11.70)\n•AESIs (n=28)\n–29 COVID -19 illnesses (unrelated): Sim Group* (n=18) SeqGroup* (n=9)  \n–1 allergic type reaction (possibly related): Sim Group (n=1)\n*One person in each group reported 2 COVID -19 illness events\nExploratory Objective\n•Objective : To compare the change of health -related quality of life (HRQOL) from \nbaseline in the Simultaneous versus Sequential groups following the Vaccination \nVisit 1\n24\n\nLimitations\n•Most data come from use of bivalent Pfizer -BioNTech \nmRNA COVID -19 vaccine during one season\n–Very little use of Moderna mRNA vaccine\n•Very few children ages 5- 11 years and older adults \n≥65 years enrolled\n•Enrollment limited by COVID -19 pandemic; enrolled \n~70% of target \n•Study too small to detect rare adverse events \n•People known to be pregnant not included; a future \nCISA study assessing safety of simultaneous influenza and COVID -19 vaccines during pregnancy is planned \n25\nSummary\n•Simultaneous administration of influenza and mRNA COVID -19 vaccines is well tolerated \nwhen compared to sequential administration \n–Occurrence of moderate or more severe fever, chills, myalgia, or arthralgia was not \nhigher in the simultaneous (25.6%) vs. sequential (31.3%) group\n–No significant differences in occurrence of adverse events within 7 days, adverse events of special interest, serious adverse events, and HRQOL  \n•As previously observed in other studies injection site and systemic reactions were associated with mRNA COVID -19 vaccine and influenza vaccine; most reactions were mild \nor moderate\n–Most frequent injection site reactions after either vaccine were pain and axillary swelling/tenderness \n–Most frequent systemic reactions after COVID -19 vaccine, with or without influenza vaccine, were fatigue, \nmyalgia, headache, chills and arthralgia \n–Receipt of influenza vaccine alone was associated chills, fatigue, myalgia and diarrhea\n26\nAcknowledgements\n•Duke University (Duke)\n–Principal Investigator: Emmanuel B. Walter, MD, MPH\n–Investigators: Ken Schmader MD,  Wes Rountree , MPH , Marek S. Poniewierski MD, MS , \nRachel L. Spreng PhD\n•John Hopkins University (JHU)\n–Principal Investigator: Kawsar Talaat, MD\n•Cincinnati Children’s Hospital Medical Center (CCHMC)\n–Principal Investigator: Elizabeth Schlaudecker, MD, MPH \n–Investigator: Mary Staat, MD, MPH\n•CDC\n–Principal Investigator: Karen Broder, MD\n–Investigators: Jonathan Duffy, MD, MPH, Oidda Museru MSN, MPH, Lisa A. Grohskopf \nMD, MPH, Anju Goel MD, MPH (contractor)\n27\nExtra Slides\n28\nSerious Adverse Event (SAE) Definition\n•An SAE is defined as an AE that meets one of the following conditions:\n–Results in death during the period of protocol -defined surveillance \n–Is life -threatening (defined as immediate risk of death at the time of the event)\n–Requires inpatient hospitalization or prolonged hospitalization during the period of \nprotocol -defined surveillance \n–Results in congenital anomaly or birth defect\n–Results in a persistent or significant disability/incapacity\n–Any other important medical event that may not result in death, be life threatening, or require hospitalization, may be considered an SAE when, based upon appropriate medical judgment, the event may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed above. Examples of such medical events include allergic bronchospasm requiring intensive treatment in an emergency room or at home, blood dyscrasias or convulsions that do not result in \ninpatient hospitalization, or the development of drug dependency or drug abuse.\n29\nAdverse Event of Special Interest (AESI) \nDefinition\n•An AESI includes the following:\n–COVID -19 illness  \n–Multisystem inflammatory syndrome  \n–Guillain -Barre syndrome\n–Allergic type reactions (including anaphylaxis, hives, or facial \nand limb swelling occurring within 7 days of a vaccination visit)\n–Myocarditis or pericarditis \n30\nInjection Site Reactions Grading\n31Table 8. Injection-site Reactogenicity Grading \nLocal Reaction to \nInjectable Product Mild (Grade 1) Moderate (Grade 2) Severe (Grade 3) Potentially Life Threatening (Grade 4)\nPain\nNoticeable but does \nnot interfere with \nactivityInterferes with activity \nbut did not need a \nmedical visit or \nabsenteeism [i.e. \nmissing work or \nschool]Significant; prevents \ndaily activity and/or \nresulted in medical visit \nand/or absenteeism [i.e. \nmissing work or school]Requires an emergency room (ER) \nvisit or hospitalization\nInduration/Swelling\n(≥ 12 years of age)2.5 –5 cm 5.1 –10 cm > 10 cmRequires an emergency room (ER) \nvisit or hospitalization\nInduration/Swelling(< 12 years of age)0.5 –2 cm 2.0 -7.0 cm > 7 cmRequires an emergency room (ER) \nvisit or hospitalization\nErythema/Redness(≥ 12 years of age)2.5 –5 cm 5.1 –10 cm > 10 cmRequires an emergency room (ER) \nvisit or hospitalization\nErythema/Redness(< 12 years of age) 0.5 –2 cm 2.0 -7.0 cm > 7 cmRequires an emergency room (ER) \nvisit or hospitalization\nAxillary (underarm) \nswelling or tenderness ipsilateral to side of injection Noticeable but does \nnot interfere with \nactivityInterferes with activity \nbut did not need a \nmedical visit or \nabsenteeism [i.e. \nmissing work or \nschool]Significant; prevents \ndaily activity and/or \nresulted in medical visit \nand/or absenteeism [i.e. \nmissing work or school] Requires an emergency room (ER) \nvisit or hospitalization\nSystemic Reactions Grading\n32Table 9. Systemic Reactogenicity Grading (FDA modified)\nSystemic Mild (Grade 1) Moderate (Grade 2) Severe (Grade 3)Potentially Life Threatening \n(Grade 4)\nFever (°C)\n(°F)38.0 -38.4\n100.4 -101.1  38.5 -38.9 \n101.2 -102.0 39.0 –40.0  \n102.1- 104.0> 40.0  \n>104.0\nNausea/vomitingNoticeable but does not interfere \nwith activity or 1 –2 episodes/24 \nhoursSome interference with activity or \n> 2 episodes/24 hoursSignificant; prevents daily activity and/or resulted in medical visit \nand/or absenteeism [i.e. missing work or school]Requires an ER visit or \nhospitalization \nDiarrheaNoticeable but does not interfere \nwith activity or 2 –3 loose stools/24 \nhoursSome interference with activity or \n4-5 loose stools/24 hoursSignificant; prevents daily activity \nand/or resulted in medical visit \nand/or absenteeism [i.e. missing work or school] or 6 or more watery stools or > 24 hoursRequires an ER visit or \nhospitalization\nHeadacheNoticeable but does not interfere \nwith activitySome interference with activity but did not need a medical visit or absenteeism [i.e. missing work or school]Significant; prevents daily routine \nactivity and/or resulted in medical \nvisit and/or absenteeism [i.e. missing work or school]Requires an ER visit or hospitalization\nFatigueNoticeable but does not interfere \nwith activit ySome interference with activity but \ndid not need a medical visit or \nabsenteeism [i.e. missing work or \nschool]Significant; prevents daily routine \nactivity and/or resulted in medical \nvisit and/or absenteeism [i.e. missing work or school]Requires an ER visit or \nhospitalization\nMyalgia Noticeable but does not interfere \nwith activitySome interference with activity but \ndid not need a medical visit or \nabsenteeism [i.e. missing work or school]Significant; prevents daily routine \nactivity and/or resulted in medical \nvisit and/or absenteeism [i.e. missing work or school]Requires an ER visit or \nhospitalization\nArthralgiaNoticeable but does not interfere \nwith activitySome interference with activity but \ndid not need a medical visit or \nabsenteeism [i.e. missing work or \nschool]Significant; prevents daily routine \nactivity and/or resulted in medical \nvisit and/or absenteeism [i.e. missing work or school]Requires an ER visit or \nhospitalization\nChills Noticeable but does not interfere \nwith activitySome interference with activity but \ndid not need a medical visit or \nabsenteeism [i.e. missing work or \nschool] Significant; prevents daily routine \nactivity and/or resulted in medical \nvisit and/or absenteeism [i.e. missing work or school]Requires an ER visit or \nhospitalization\nEQ-5D-5L and VAS\n33\n\nSubject Inclusion Criteria\n•Persons aged ≥5 years if receiving primary two -dose mRNA COVID -19 \nvaccine series or persons aged ≥12 years if receiving a booster mRNA \nCOVID -19 vaccine dose according to FDA authorization or approval and \nACIP recommendation. Note: receipt of an mRNA COVID -19 vaccine \nwithin 8 hours of enrollment is permitted\n* Individuals age 5 -11 receiving a booster may be enrolled in the event a \nbooster for individuals age 5 -11 is authorized or approved and recommended by \nthe ACIP.\n•English or Spanish literate\n•Intention of receiving influenza vaccine and mRNA COVID -19 vaccine \nbased on ACIP -CDC guidelines\n•Willing to provide written informed consent\n•Intention of being available for entire study period and complete all relevant study procedures, including follow -up phone calls and clinic visits\n34\nSubject Exclusion Criteria\n•Currently pregnant, planning to become pregnant within the first three months of the study per \nparticipant self -report or likely to be pregnant per screening criteria as defined in protocol at Visit 1\n•Prior receipt of IIV4 during the respective influenza season in which they are being enrolled\n•< 9 years of age and recommended to receive two doses of IIV4 during the respective influenza season in which they are being enrolled \n•Prior receipt of non -mRNA COVID -19 vaccine\n•Documented COVID -19 infection within 6 weeks prior to enrollment confirmed by either medical \nhistory or lab testing \n•History of severe allergic reaction after a previous dose of any influenza vaccine; or to an influenza vaccine component, including egg protein\n•History of severe adverse reaction associated with a vaccine and/or severe allergic reaction (e.g. anaphylaxis) to any component of an mRNA vaccine\n•Receipt of any licensed inactivated vaccine within 2 weeks prior to enrollment in this study, receipt of any licensed live vaccine within 4 weeks prior to enrollment in this study, or receipt of Shingrix\n(Zoster Vaccine Recombinant, Adjuvanted) or HEPLISAV -B (Hepatitis B Vaccine (Recombinant), \nAdjuvanted) vaccine within 6 weeks prior to enrollment in this study or planning receipt of any vaccines following enrollment until 6 weeks after receipt of the second dose of mRNA COVID -19 \nvaccine\n35\nSubject Exclusion Criteria\n•Has an active neoplastic disease (excluding non -melanoma skin cancer or prostate cancer that is \nstable in the absence of therapy) or a history of any hematologic malignancy*\n*Participants with a history of malignancy may be included if, after previous treatment by surgical excision, \nchemotherapy or radiation therapy, the participant has been observed for a period that in the investigator’s \nestimation provides a reasonable assurance of sustained cure\n•Thrombocytopenia, bleeding disorder, or anticoagulant use contraindicating intramuscular injection (a \ndaily aspirin may be acceptable).  \n•Has immunosuppression as a result of an underlying illness or medications, such as antirejection/transplant regimens or immunomodulatory agents. Stable HIV disease is permitted per \nthe following parameters:\n–Confirmed stable HIV disease defined as document viral load <50 copies/mL and CD4 count \n>200 within 6 months before enrollment, and on stable antiretroviral therapy for at least 6 \nmonths\n•Has known hepatitis B (HBV) or hepatitis C (HBC). Stable HBV or HBC are permitted per the following \nparameters:\n–If known HBV: confirmed inactive chronic HBV infection:  HBsAg present for ≥6 months and \nHBeAg negative, anti- HBepositive; serum HBV DNA <2000 IU/mL; persistently normal ALT or \nAST levels; in those who had liver biopsy, findings that confirm absence of significant necroinflammation\n–If known HCV: evidence of sustained virological response for ≥12 weeks after treatment or \nwithout evidence of HCV RNA viremia (undetectable HCV RNA)\n36\nSubject Exclusion Criteria\n•Use of oral, parenteral, or high -dose inhaled glucocorticoids*\n*For definition of high -dose inhaled glucocorticoids, reference Appendix B.\n•History of Guillain -Barré syndrome \n•Prior enrollment in this study during the 2021 -22 flu season\n•Anyone who is already enrolled or plans to enroll in another clinical trial with an \ninvestigational product during the study period.* \n*Per protocol, co- enrollment in observational or behavioral intervention studies are permitted at \nany time. An investigational product may be permitted for therapy of an illness condition that \noccurs during the study period e.g. COVID -19 illness.\n•Hearing loss determined by the investigators to prevent successful communication over \nthe phone\n•History of myocarditis or pericarditis \n•History of multisystem inflammatory syndrome in children (MIS -C) or adults (MIS -A).  \n•Has injury or other reason why deltoid site on both arms cannot be used for vaccinations. \n•Any condition which, in the opinion of the investigators, may pose a health risk to the subject or interfere with the evaluation of the study objectives.  \n•Anyone who is a relative of any research study personnel.  \n•Anyone who is an employee of any research study personnel.    \n37", "summary": "Safety of Simultaneous versus Sequential  Administration of mRNA COVID -19 and Quadrivalent Inactivated Influenza (IIV4)  Vaccines: A Randomized Placebo Controlled Trial (ClinicalTrials.gov ID: NCT05028361) Emmanuel “Chip” Walter MD, MPH ACIP October 25, 2023 Disclaimer •The findings and conclusions in this presentation are  those of the presenter and do not necessarily represent the official position of the Centers for Disease Control and Prevention •Mention of a product or company name is…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-25-26-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-10-25-26/04-Influenza-Walter-508.pdf", "doc_date": "2023-10-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 37}
{"title": "05 Influenza Schmader 508", "content": "Kenneth Schmader, MD\nACIP Meeting\nOctober 25, 2023 Safety of Simultaneous Vaccination with Zoster \nVaccine Recombinant (RZV) and Quadrivalent \nAdjuvanted Inactivated Influenza Vaccine (allV4)\n(ClinicalTrials.gov ID: NCT05007041)\nDisclaimer\n•The findings and conclusions in this \npresentation are those of the presenter and do not necessarily represent the official position of the Centers for Disease Control and Prevention\n•Mention of a product or company name is for identification purposes only and does not constitute endorsement by CDC\n•This study was supported by the CDC Clinical Immunization Safety Assessment (CISA) Project \n2\n•Duke University\n–Principal Investigator: Kenneth Schmader, MD \n–Investigators: Emmanuel B. Walter, MD, MPH, Wes Rountree , MPH , \nMarek S. Poniewierski MD, MS\n•CDC\n–Principal Investigator: Karen Broder, MD\n–Investigators: Michael McNeil, MD, MPH, Oidda Museru MSN, MPH\n•John Hopkins University (JHU)\n–Principal Investigator: Kawsar Talaat, MDStudy Team\n3\nRationale\n•Novel (nonaluminum) adjuvants are powerful immune \nstimulants employed in vaccine platforms to improve immunogenicity and efficacy.  In recent years, the FDA licensed several vaccines with novel adjuvants\n•Vaccines with novel adjuvants are more reactogenic than \nvaccines without adjuvants.\n•Clinicians may opt to administer these vaccines simultaneously. \n•Data are needed on the safety of the simultaneous administration of vaccines with novel adjuvants\n•For older adults seeking to prevent herpes zoster and influenza, data are needed on the safety of simultaneous administration of recombinant zoster vaccine (RZV; Shingrix) and quadrivalent adjuvanted inactivated influenza vaccine \n(aIIV4; Fluad Quadrivalent)  \n4\nStudy Design and Population \n•Type: \n–Prospective, randomized, observer blinded clinical trial \n–Blinded except for vaccine administrator \n•Population: \n–Immunocompetent, cognitively intact, community -dwelling persons, \naged ≥65 years\n–Not received the seasons flu vaccine or RZV\n–Subjects enrolled at Duke University Medical Center (Lead Site) and \nJohns Hopkins University (Contributing Site) during the 2021 -2022 \nand 2022- 2023 flu seasons \n•Intervention:\n–Randomized 1:1 to receive either <RZV and aIIV4> or <RZV and HD -\nIIV4*>\n•Study visit schedule (summary):\n–Day 1: receive RZV dose 1 and influenza vaccine simultaneously  \n–Day 60:receive RZV dose 2\n–Day 103:complete study  \n–Safety outcomes collected throughout study; blood collected for influenza immunogenicity assessment (lab analysis not completed) \n5*quadrivalent high- dose inactivated influenza vaccine (Fluzone High -dose Quadrivalent)\nAnalysis Populations\n6Intention -to-Treat (ITT) Population: defined as all \nsubjects who are randomized and vaccinated (received at \nleast one study vaccine). \nModified Intention- to-Treat ( mITT ) Population: defined \nas all subjects who are randomized, vaccinated (received at \nleast one study vaccine), and provide at least one day of \ncomplete data on the symptom diary. \nConsort Diagram\n7\n\nDemographic Summary \n8Characteristic Fluzone -HD (n=137) FLUAD (n=130) Total (N= 267) \nGender\nMale \nFemale 68 (49.6%)\n69 (50.4%)69 (53.1%)61 (46.9%)137 (51.3%)130 (48.7%)\nRace \nWhite Only\nBlack Only \nOther124 (90.5%)\n12 (8.8%)\n1 (0.7%)123 (94.6%)\n7 (5.4%)0 (0.0%) 247 (92.5%)\n19 (7.12%)\n1 (0.37%)\nEthnicity\nHispanic or Latino\nNon -Hispanic or Latino\nUnknown1 (0.7%)\n134 (97.8%)\n2 (1.5%)2 (1.5%)\n128 (98.5%)\n0 (0.0%)3 (1.12%)\n262 (98.1%)\n2 (0.75%)\nAge \n65-69 \n70 or more48 (35%)89 (65%)44 (33.8%)86 (66.2%)92 (34.5%)\n175 (65.5%)\nPO1: To compare the proportion of participants \nwith at least one severe (Grade 3) solicited local or systemic reactogenicity event after RZV dose 1 in the RZV and aIIV4 group versus RZV and HD- IIV4 \ngroup.   \nHypothesis: The proportion of participants with at \nleast one severe (Grade 3) solicited reactogenicity event will be noninferior (not higher) in the RZV and aIIV4 group compared with the RZV and HD -\nIIV4 group. Primary Objective  \n9\nOutcome : Proportion of participants with at least one \nsevere (Grade 3) solicited local or systemic \nreactogenicity event on days 1- 8 after RZV dose 1 in \neach study group \n*Met noninferiority objective with a 10% noninferiority margin, the upper bound is \nless than 10%. The confidence interval contains 0, so there is no claim of superiority. Primary Outcome: mITT Population\n101+ Grade 3 Event\nNo Yes Noninferiority Test 10% Margin\nGroup N % N % Diff Lower CI Upper CI p-value\nFLUAD 115 88.46 15 11.54 . . . .\nFluzone -HD 119 87.50 17 12.50 -0.0096 -0.0894 0.0710 0.0037\nSecondary Objectives \n•SO1: To compare the proportion of participants with at \nleast one severe (Grade 3) solicited local reactogenicity \nevent after RZV dose 1 in the RZV and aIIV4 group vs. RZV \ndose 1 and HD -IIV4 group (non -inferiority analysis) \n•SO2: To compare the proportion of participants with at \nleast one severe (Grade 3) solicited systemic reactogenicity \nevent after RZV dose 1 in the RZV and aIIV4 group vs. RZV \ndose 1 and HD -IIV4 group (non -inferiority analysis)\n•SO3: To compare the proportion of participants with at \nleast one serious adverse event or adverse event of clinical \ninterest after RZV dose 1 in the RZV and aIIV4 group vs. \nRZV dose 1 and HD -IIV4 group through Day 43 and \ndescribe these events (95% confidence interval (CI) \ncomparison)\n11\nSO1: Proportion of participants with at least one severe (grade 3) \nsolicited local reactogenicity event on days 1 -8 after RZV dose 1 in \neach study groupSecondary Outcome SO1:mITT Population\n121+ Grade 3 Event\nNo Yes Noninferiority Test 10% Margin\nGroup N % N % Diff Lower CI Upper CI p-value\nFLUAD 122 93.85 8 6.15 . . . .\nFluzone -HD 130 95.59 6 4.41 0.0174 -0.0404 0.0777 0.0031\n*Met noninferiority objective with a 10% noninferiority margin, the upper bound is \nless than 10%. The confidence interval contains 0, so there is no claim of superiority.\nSO2: Proportion of participants with at least one severe (grade 3) \nsolicited systemic reactogenicity event on days 1 -8 after RZV dose \n1 in each study group\n*Met noninferiority objective with a 10% noninferiority margin, the upper bound is \nless than 10%. The confidence interval contains 0, so there is no claim of superiority Secondary Outcome SO2:mITT Population\n131+ Grade 3 Event\nNo Yes Noninferiority Test 10% Margin\nGroup N % N % Diff Lower CI Upper CI p-value\nFLUAD 123 94.62 7 5.38 . . . .\nFluzone -HD 123 90.44 13 9.56 -0.0417 -0.1090 0.0247 <.0001\n020406080100\naIIV4 HD-IIV4 aIIV4 HD-IIV4 aIIV4 HD-IIV4 aIIV4 HD-IIV4 aIIV4 HD-IIV4 aIIV4 HD-IIV4\nPain Swelling Redness Pain Swelling RednessPercent\n----------------- RZV Vaccine ----------------- ----------------- Flu Vaccine -------------- ---\nSolicited Event and GroupLocal Reactions:  RZV Dose 1 and Influenza Vaccines\nMild Moderate Severe\nNo significant differences in proportion of moderate/severe local reactogenicity events between aIIV4 and HD- IIV4 groups    \n020406080100\naIIV4 HD-IIV4 aIIV4 HD-IIV4 aIIV4 HD-IIV4 aIIV4 HD-IIV4 aIIV4 HD-IIV4 aIIV4 HD-IIV4 aIIV4 HD-IIV4 aIIV4 HD-IIV4 aIIV4 HD-IIV4 aIIV4 HD-IIV4\nFever Chills Fatigue Myalgia Headache Arthralgia Nausea Vomiting Diarrhea Abdominal PainPercent\nSolicited Event and GroupSystemic Reactions:  RZV Dose 1 and Influenza Vaccines\nMild Moderate Severe\nNo significant differences in proportion of moderate/severe systemic reactogenicity events between aIIV4 and HD- IIV4 groups    \nSO3: Proportion of participants with at least one serious \nadverse event or adverse event of clinical interest after RZV \ndose 1 within 43 days. Secondary Outcome SO3: ITT Population\nSubjects with at Least One Serious Adverse \nEvent (SAE) Within 43 Days\n16At Least One Serious Adverse Event Within \n43 Days \nNo Yes Percent YesFLUAD -Fluzone -HD    \n95% CI of the Difference\nGroup N % N % 95% CI 95% CI\nFLUAD 129 99.23 1 0.77 (0.02, 4.21)\nFluzone -HD 132 96.35 5 3.65 (1.20, 8.31) -2.88 ( -6.36, 0.60)•6 Subjects reported at least one SAE within 43 Days \n•9 subjects reported at least one SAE during study period ITT Population\nAll Subjects with at Least One Serious \nAdverse Event through Entire Study Period \n17At Least One Serious Adverse Event\nNo Yes Percent YesFLUAD -Fluzone -HD\n95% CI of the Difference\nGroup N % N % 95% CI 95% CI\nFLUAD 126 96.92 4 3.08 (0.84, 7.69)\nFluzone -HD 132 96.35 5 3.65 (1.20, 8.31) -0.57 ( -4.89, 3.75)\nSummary of SAEs within 43 days of RZV dose 1 and \ninfluenza vaccination* \n18Group Age group \nyearsRelatedness Clinical description\naIIV4 ≥70 Not related Pacemaker due to arrhythmia\nHD-IIV4 65-69 Not related Numbness, Cerebrovascular\naccident (CVA)\nHD-IIV4 ≥70 Not related Acute hyperkalemia\nHD-IIV4  ≥70 Not related Shortness of breath\nHD-IIV4 ≥70 Not related Acute pulmonary embolism and \nacute deep vein thrombosis \nHD-IIV4 65-69 Possibly related Left partial cranial\nnerve III palsy\n*All participants with SAE required hospitalization or had prolongation of hospitalization; no deaths\n19*All participants with SAE required hospitalization or had prolongation of hospitalization; no deathsSummary of SAEs >43 days of RZV dose 1 and \ninfluenza vaccination * \nGroup Age group \nyearsRelatedness Clinical description\naIIV4 ≥70 Not related Heptocellular carcinoma \naIIV4 ≥70 Not related Revision of right shoulder rotator \ncuff surgery \naIIV4 65-69 Not related Chronic obstructive pulmonary diseases (COPD) exacerbation \nSafety Assessments: Adverse Events\n•Pre-specified Adverse Events of Special \nInterest (AESI)\n–Syncope during the post -vaccination \nmonitoring period in clinic: none \n–Anaphylaxis in the first 24 hours after \nimmunization: none\n–New-onset immune -mediated disease during \n42 days after vaccination: one case of partial cranial nerve III palsy (also considered an SAE): patient was in the HD- IIV4 group \n20\nExploratory Objective\n•Objective : To describe and compare changes in health- related quality of life \nafter RZV dose 1 and aIIV4 with RZV dose 1 and HD -IIV4\n21Average EQ-5D-5L Index by Treatment Group\n0.00.10.20.30.40.50.60.70.80.91.0\nDays After RZV Dose 1PreVax 1 2 3 4 5 6 7 8Plot of Average EQ-5D-5L Index by Treatment Group per Day\nAll Subjects and Any Grade 3 Reactogenicity Event After RZV Dose 1: N=32\nFLUAD: All Subjects FLUAD: N=32 Subjects\nFluzone-HD: All Subjects Fluzone-HD: N=32 Subjects\nAverage Visual Analogue Scale (VAS) by Treatment Group0.0 10 20 30 40 50 60 70 80 90100\nDays After RZV Dose 1PreVax 1 2 3 4 5 6 7 8Plot of Average Visual Analogue Scale (VAS) by Treatment Group per Day\nAll Subjects and Any Grade 3 Reactogenicity Event After RZV Dose 1: N=32\nFLUAD: All Subjects FLUAD: N=32 Subjects\nFluzone-HD: All Subjects Fluzone-HD: N=32 Subjects\nLimitations\n•Enrollment limited by COVID -19 \npandemic; enrolled ~70% of target\n•Study population mostly white, non-\nHispanic  \n•Study too small to detect rare \nadverse events \n22\nConclusion\n•The proportion of participants with at least one severe \nlocal or systemic reaction was not higher after RZV dose 1 and aIIV4 (11.5%) compared to RZV dose 1 and HD -IIV4 (12.5%)   \n•The frequency of moderate-severe local and systemic reactogenicity events were similar when RZV dose 1 was administered with aIIV4 or HD -IIV4 \n•Few participants had serious adverse events during the study after RZV dose 1 was administered with aIIV4 (3.1%) or HD -IIV4 (3.7%); the clinical \nconditions were those expected in a population of \nolder adults\n•From a safety standpoint, this study supports \nsimultaneous administration of RZV and aIIV4 as an acceptable option for vaccine delivery in older adults\n23\nExtra Slides\n24\nSerious Adverse Event Definition \n•An SAE is defined as an adverse event that results in \none of the following: \n–Death\n–Is life threatening\n–Hospitalization or prolongation of existing \nhospitalization \n–Persistent or significant disability/incapacity \n–Important medical events that may jeopardize the subject's health and may require medical or surgical intervention to prevent one of the other outcomes listed in this (SAE) definition \n25\nInjection Site Reactions Grading\n26Injection- site Reactogenicity\nSymptom Mild (Grade 1) Moderate (Grade 2) Severe (Grade 3)\nPain Any pain neither interfering with \nnor preventing normal every \nday activities.Painful when limb is moved and\ninterferes with every day \nactivities.Significant pain at rest. \nPrevents\nnormal every day activities.\nInduration/\nSwelling≥20 mm to ≤50 mm diameter > 50 mm to ≤ 100 mm diameter > 100 mm diameter\nErythema \n(Redness)≥20 mm to ≤50 mm diameter > 50 mm to ≤ 100 mm diameter > 100 mm diameter\nSystemic Reactions Grading\n27\n\nEQ-5D-5L and VAS\n28\n\nSubject Inclusion Criteria\n•Male or female age ≥ 65 years\n•Intention of receiving IIV and RZV based on ACIP-\nCDC guidelines\n•Able to speak English \n•Willing to provide written informed consent\n•Living in the community\n•Intention of being available for entire study period and complete all relevant study procedures, including follow -up phone calls and clinic visits.\n•If HIV positive, HIV should be clinically stable\n29\nSubject Exclusion Criteria\n•IIV or recombinant influenza vaccine (RIV) receipt during the respective 2021 -2022 or 2022 -2023 influenza \nseason prior to study enrollment\n•Prior receipt of recombinant zoster vaccine ( Shingrix )\n•For non -COVID -19 Vaccines: \n–Receipt of any inactivated vaccine within 2 weeks prior to enrollment in this study\n–Receipt of any live vaccine within 4 weeks prior to enrollment in this study\n–Planning receipt of any non -COVID -19 vaccine during the entire period \n•For COVID -19 Vaccines: \n–Receipt of COVID -19 vaccine within 2 weeks prior to enrollment in this study. For those who have initiated a \nCOVID -19 vaccine series, enrollment is not allowed until 2 weeks after the final dose of a COVID -19 vaccine is \ncompleted.  \n–Planning receipt of a COVID -19 vaccine within 2 weeks after administration of study influenza and first dose \nrecombinant zoster study vaccines. \n•Have acute illness or exacerbation of chronic illness within 72 hours of study vaccination \n•Hospitalization within the last 30 days for any reason \n•History of febrile illness (> 100.0 °F or 37.8 °C) within the past 24 hours prior to IIV administration\n•Has immunosuppression as a result of an underlying illness or treatment, or use of chemotherapy or radiation \ntherapy within the preceding 12 months\n•Has an active neoplastic disease (excluding non- melanoma skin cancer or prostate cancer that is stable in the \nabsence of therapy) *Participants with a history of malignancy may be included if, after previous treatment by surgical excision, chemotherapy or radiation therapy, the participant has been observed for a period that in the investigator’s estimation provides a reasonable assurance of sustained cure \n•A history of autoimmune disease, that requires immunosuppressive agents or any other chronic medical condition considered clinically significant by the investigator \n30\nSubject Exclusion Criteria\n•Use of chronic oral or intravenous administration (≥14 days) of immunosuppressive doses of \nsteroids, i.e., prednisone >10 mg per day, immunosuppressants or other immune-modifying \ndrugs within 30 days of starting this study. (Use of topical, nasal, or inhaled steroids is permitted) \n•Thrombocytopenia, bleeding disorder, or anticoagulant use contraindicating intramuscular injection (a daily aspirin may be acceptable)\n•Contraindication to IIV receipt including history of severe allergic reaction after a previous dose of any influenza vaccine; or to a vaccine component, including egg protein\n•Contraindication to RZV including history of a severe allergic reaction to any component of the RZV vaccine (including saponin or polysorbate 80) or to dose 2 of RZV\n•History of Guillain -Barré syndrome\n•History of Hepatitis C or active Hepatitis B\n•Receipt of blood or blood -derived products (including immunoglobulin) within 6 months prior \nto study vaccination  \n•Dementia, any cognitive condition, or substance abuse that could interfere with study compliance\n•Anyone who is already enrolled or plans to enroll in another clinical trial with an investigational product within 28 days of vaccine receipt. Co -enrollment in observational or \nbehavioral intervention studies are allowed at any time while enrollment in a clinical trial involving an investigational product (other than vaccine) may occur after 28 days following vaccine receipt\n•Any condition which, in the opinion of the investigators, may pose a health risk to the subject or interfere with the evaluation of the study objectives\n•Anyone who is a relative of any research study personnel\n•Anyone who is an employee of any research study personnel\n31", "summary": "Kenneth Schmader, MD ACIP Meeting October 25, 2023 Safety of Simultaneous Vaccination with Zoster  Vaccine Recombinant (RZV) and Quadrivalent  Adjuvanted Inactivated Influenza Vaccine (allV4) (ClinicalTrials.gov ID: NCT05007041) Disclaimer •The findings and conclusions in this  presentation are those of the presenter and do not necessarily represent the official position of the Centers for Disease Control and Prevention •Mention of a product or company name is for identification purposes only…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-25-26-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-10-25-26/05-Influenza-Schmader-508.pdf", "doc_date": "2023-10-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 31}
{"title": "01 VaxSafety Shimabukuro 508", "content": "National Center for Emerging and Zoonotic Infectious Diseases\nUpdate on COVID -19 and influenza vaccine safety\nAdvisory Committee on Immunization Practices (ACIP) meeting\nOctober 25, 2023\nTom T. Shimabukuro, MD, MPH, MBA\nDirector, Immunization Safety Office\nDivision of Healthcare Quality Promotion \nCenters for Disease Control and Prevention (CDC)\n\nKey points up front\n2▪A statistical signal for ischemic stroke after Pfizer -BioNTech bivalent mRNA COVID -19 vaccine was \ndetected in CDC’s Vaccine Safety Datalink in persons aged ≥65 years during fall 2022; information \nwas presented at prior ACIP meetings and efforts have been underway to evaluate the signal*\n▪Available data do not provide clear and consistent evidence of a safety problem for ischemic stroke \nwith bivalent mRNA COVID -19 vaccines when given alone or given simultaneously with influenza \nvaccines, or when influenza vaccine is given alone\n•Variable and inconsistent results were obtained in some analyses of the risk of ischemic stroke following \nbivalent mRNA COVID -19 vaccination, simultaneous bivalent mRNA COVID -19 and influenza vaccination, \nand influenza vaccination alone†\n•Most study results have not shown an association between vaccination and ischemic stroke, and no clear \npattern demonstrating increased risk has emerged\n▪Any real or theoretical risks of vaccine adverse events need to be placed in the context of the \nknown benefits of COVID -19 and influenza vaccination in preventing COVID -19 and influenza \ndisease and their potentially serious complications, including stroke\n▪Our vaccine safety monitoring systems are designed to be sensitive, and the detection and \nassessment of potential safety signals and communication of safety information to the public is an \nexample of the vaccine safety monitoring process working  \n* https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2023 -02/slides -02-24/COVID -02-Shimabukuro -508.pdf ; \nhttps://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2023 -04-19/03 -COVID -Shimabukuro -508.pdf\n†For the purpose of this presentation, “influenza vaccination alone” is defined as not with simultaneous COVID -19 vaccination bu t may include other types of non -COVID -19 vaccines     \nTopics\n▪Summary of analyses of ischemic stroke and bivalent mRNA COVID -19 \nand influenza vaccination\n▪Additional data on ischemic stroke\n▪Interpretation of data on ischemic stroke and bivalent mRNA COVID -\n19 and influenza vaccination and next steps\n3\nSelected analyses of ischemic stroke and bivalent COVID -19 and \ninfluenza vaccination\n1.Vaccine Safety Datalink (VSD) Rapid Cycle Analysis (RCA) of ischemic stroke after bivalent\nmRNA COVID -19 vaccination (Centers for Disease Control and Prevention)\n2.Analysis of ischemic stroke after bivalent mRNA COVID -19 vaccination (Kaiser Permanente\nSouthern California)\n3.Analysis of stroke risk following bivalent mRNA COVID -19 vaccination among U.S. adults aged\n≥65 years in CMS data (U.S. Food and Drug Administration)\n4.Analysis of ischemic stroke after bivalent mRNA COVID -19 vaccination in patients aged ≥65\nyears using nation -wide patient electronic health records (Case Western Reserve University\nSchool of Medicine)\n5.Analysis of stroke, myocardial infarction, and pulmonary embolism after bivalent Pfizer -\nBioNTech COVID -19 vaccination (EPI -PHARE Scientific Interest Group, France)\n6.Analysis of bivalent mRNA COVID -19 vaccination and stroke in England (UK Health Security\nAgency and the London School of Hygiene and Tropical Medicine)\n7.Analysis of the safety of monovalent and bivalent Pfizer -BioNTech COVID -19 vaccination in at -\nrisk populations (Israel)\n4\n1.) VSD COVID -19 Rapid Cycle Analysis: Analyses of Ischemic Stroke \nafter Pfizer -BioNTech Bivalent Booster Dose*\n(April 2023 ACIP https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2023 -04-19/03 -COVID -Shimabukuro -508.pdf )\n▪Data source: VSD data contributing sites\n▪Methodology\n•Primary : Vaccinated concurrent comparator (i.e., bivalent vaccinated vs. bivalent vaccinated) using a \n1–21-day risk interval and a 22 –42-day comparison interval \n•Supplemental : Bivalent vaccinated vs. bivalent unvaccinated but eligible for bivalent vaccine in a 1 –\n21-day risk interval\n•Age groups included 18 –64 and ≥65 years\n▪Main findings\n•Statistical signal for ischemic stroke detected in primary analysis after Pfizer -BioNTech in the age \ngroup ≥65 years using a 1 –21-day risk interval; signal attenuated over time\n•Post -signal assessment detected an elevated risk in the age group ≥65 years receiving same -day \nPfizer -BioNTech and high -dose inactivated influenza (HD -IIV4) or adjuvanted inactivated influenza \nvaccine (aIIV4); finding attenuated over time\n•No elevated risk for ischemic stroke detected in supplemental analysis using secondary comparators\n•Additional supplemental analyses suggested that comparison interval (22 –42 days) rates of \nischemic stroke were lower than expected    5* Conducted through the CDC Vaccine Safety Datalink Indefinite Delivery, Indefinite Quantity (IDIQ) contract\n2.) Ischemic Stroke after Bivalent COVID -19 Vaccination: A Self -\nControlled Case Series Study*\n(Xu et al., 2023 https://www.medrxiv.org/content/10.1101/2023.10.12.23296968v1 )\n6▪Data source: Kaiser Permanente Southern California electronic health record data\n▪Methodology\n•Modified self -controlled case series using age groups ≥12, 12 –64 and ≥65 years \n▪Main findings\n•No elevated risks detected for either Pfizer -BioNTech or Moderna in any age groups in automated data \nwith a 21 -day risk interval\n•No elevated risks detected for either Pfizer -BioNTech or Moderna in the age group ≥65 years in automated \ndata with a 42 -day risk interval\n•There were several analyses with statistically significant elevated risks in the age group 12 –64 years in \nautomated data with a 42 -day risk interval\n‒Pfizer -BioNTech and simultaneous influenza vaccination, overall and in those with a history of SARS -\nCoV-2 infection \n‒Moderna in those with a history of SARS -CoV-2 infection\n•After limiting signaling analyses to chart -verified cases, the findings were no longer statistically significant\n* Funding provided through NIAID/NIH Award Number R01 AI168209\n3.) Evaluation of Stroke Risk Following COVID -19 mRNA Bivalent \nVaccines Among U.S. Adults Aged ≥65 Years*\n(Lu et al., 2023 https://www.medrxiv.org/content/10.1101/2023.10.10.23296624v1 )\n7▪Data source: Medicare claims data \n▪Populations: Community -dwelling Medicare beneficiaries aged ≥65 years\n•Primary population: Recipients of bivalent mRNA COVID -19 vaccine\n•Secondary population: Recipients of high -dose (HD -IIV4) or adjuvanted (aIIV4) influenza vaccine\n▪Methodology: Modified self -controlled case series with Farrington adjustment \n▪Main findings\n•Primary population analyses showed no consistent stroke risk after mRNA COVID -19 vaccination\n•An increased risk was observed with concomitant (same day administration) influenza vaccination \n‒Non -hemorrhagic stroke after Pfizer -BioNTech + HD -IIV4/aIIV4 with a 22 –42-day risk interval \n‒Transient ischemic attack after Moderna + HD -IIV4/aIIV4 with a 1 –21-day risk interval\n•Secondary population analyses showed a small increased risk of non -hemorrhagic stroke after \nHD-IIV4 or aIIV4 with a 22 –42-day risk interval, and the risk remained for people without \nconcomitant bivalent mRNA COVID -19 vaccination \n* Funding provided by the FDA as part of the SafeRx Project, a joint initiative of the CMS and FDA\n4.) Ischemic stroke after COVID -19 bivalent vaccine administration \nin patients aged 65 years and older: analysis of nation -wide \npatient electronic health records in the United States*\n(Gorenflo et al., 2023 https://www.medrxiv.org/content/10.1101/2023.02.11.23285801v1 )\n8▪Data source: TriNetX , a cloud -based analytics platform that includes electronic \nhealth record data from >90 million unique patients in the United States\n▪Methodology\n•Retrospective cohort study among people aged ≥65 years \n▪Main findings\n•Patients who received bivalent Pfizer -BioNTech COVID -19 vaccination had a similar \nhazard for ischemic stroke encounters compared to those who received bivalent \nModerna COVID -19 vaccination, but had a lower hazard than those who received the \nmonovalent Pfizer -BioNTech or Moderna COVID -19 booster vaccines in the 1 –21 or   \n22–42 days post -vaccination\n* Support provided through NIA/NIH (grants nos. RF1AG076649), NIAAA/NIH (grant no. R01AA029831), CTSC of Cleveland (grant no. 1UL1TR002548)\n5.) Stroke, Myocardial Infarction, and Pulmonary Embolism \nafter Bivalent Booster \n(Jabagi et al., 2023 https://www.nejm.org/doi/full/10.1056/NEJMc2302134 )\n9▪Data source: French National Health Data System linked to the national coronavirus\ndisease 2019 (Covid -19) vaccination database\n▪Methodology\n•Matched cohort study (1:5) in people aged ≥50 years\n•Recipient of monovalent vaccine matched to recipients of bivalent mRNA COVID -19\nvaccine*; followed for 21 days after vaccination\n▪Main findings\n•Compared to monovalent Pfizer -BioNTech COVID -19 vaccination, bivalent Pfizer -BioNTech\nCOVID -19 vaccination was not associated with an increased risk of ischemic stroke,\nhemorrhagic stroke, myocardial infarction, or pulmonary embolism in people aged ≥50 years\n•The authors previously found no increase in the incidence of stroke, acute myocardial\ninfarction, or pulmonary embolism after administration of the monovalent Pfizer -BioNTech\nCOVID -19 vaccine\n*contains omicron BA.4 –BA.5 strains; used in the United States \n6.) BA.1 Bivalent COVID -19 Vaccine Use and Stroke in England*\n(Andrews et al., 2023 https://jamanetwork.com/journals/jama/fullarticle/2806456 )\n10▪Data source: National Health Service hospital admissions in England linked to the \nNational Immunisation Management System\n▪Methodology\n•Self-controlled case -series design in people aged ≥50 and ≥65 years (1 –21-day risk \nwindow) with further analysis in people aged ≥65 years given simultaneous bivalent mRNA \nCOVID -19†and influenza vaccination‡\n▪Main findings\n•No increased risk of stroke in the 21 days after vaccination with either the Pfizer -BioNTech \nor the Moderna bivalent mRNA COVID -19 vaccines\n•Similar results obtained for ischemic and hemorrhagic stroke for the subset of people aged \n≥65 years given influenza vaccine on the same day as the bivalent mRNA COVID -19 vaccine \n* Funded by the UK Health Security Agency; † Contains omicron BA.1 strain; not used in United States; ‡persons aged ≥ 65 years 95% received quadrivalent or \ntrivalent adjuvanted influenza vaccine (no high -dose influenza vaccine used)\n7.) Safety of monovalent and bivalent BNT162b2 mRNA COVID -19 \nvaccine boosters in at -risk populations in Israel: a large -scale, \nretrospective, self -controlled case series study*\n(Yamin et al., 2023 https://www.sciencedirect.com/science/article/pii/S1473309923002074?via%3Dihub )\n11▪Data source: Clalit Health Services medical records (largest healthcare \norganization in Israel with over 3.5 million enrollees, 1.2 million aged ≥60 years)\n▪Methodology\n•Self-controlled case -series\n▪Main findings\n•No safety signals detected for ischemic stroke after either monovalent or bivalent \nPfizer -BioNTech COVID -19 vaccines used in Israel in the overall analysis or in people \naged ≥65 years\n* Supported by Israel Science Foundation (grant 3409/19), within the Israel Precision Medicine Partnership\nAdditional data on ischemic stroke\n12▪No unusual or unexpected reporting patterns observed, and no evidence of a safety concern \ndetected for ischemic stroke with either of the bivalent mRNA COVID -19 vaccines in Vaccine \nAdverse Event Reporting System (VAERS) monitoring\n▪FDA monitoring in the CMS data and Department of Veterans Affairs monitoring in the VA \nsystem did not detect any safety signals for ischemic stroke following bivalent mRNA COVID -19 \nvaccination using historical comparator designs\n▪A separate ad hoc CDC analysis during the bivalent Pfizer -BioNTech ischemic stroke signal \nassessment did not detect an elevated risk for ischemic stroke after influenza vaccination alone \n▪Surveillance conducted by international regulatory and public health partners did not detect a \nsafety concern for ischemic stroke following bivalent mRNA COVID -19 vaccination \n▪No evidence of a safety signal for ischemic stroke detected in the manufacturers’ global \nmonitoring of bivalent mRNA COVID -19 vaccination\n▪No safety signals were detected for ischemic stroke for primary series or monovalent boosters \nfor Pfizer -BioNTech or Moderna COVID -19 vaccines in U.S. and global monitoring)\n▪Data suggest COVID -19 and influenza disease are associated with an increased risk of stroke \nACIP Ischemic Stroke, COVID -19 and Influenza in Adults Ages greater than or Equal to 65 years -Feb. 24, 2023 (cdc.gov)\nMonthly incidence rates of non -hemorrhagic stroke (NHS) \nin Medicare claims data suggesting seasonality*\n13\n* From eFigure 1. Monthly Incidence Rates of NHS, TIA, NHS/TIA, and HS per 100,000 Person -Years at Risk, in Lu et al., 2023 https://www.medrxiv.org/content/10.1101/2023.10.10.23296624v1\nOutpatient visits for respiratory illness in the United States from ILINet\n14\n\nInterpretation of analyses of ischemic stroke and bivalent \nCOVID -19 and influenza vaccination \n15▪Variable and inconsistent results were obtained in some analyses of risk of ischemic \nstroke following bivalent COVID -19 vaccination, simultaneous bivalent COVID -19 and \ninfluenza vaccination, and influenza vaccination alone\n•There is a lack of consistency in findings from different data systems, when using different methods, \nacross age groups, and across sub -group analyses\n•The most common findings across studies are findings of no association\n•Multiple comparisons were conducted in studies without adjusting for multiplicity; few reached \nstatistical significance\n•The studies were not designed to account for a potential protective effect of vaccination on stroke in \nlater post -vaccination periods\n•Adjusting for seasonality and restricting analyses to chart -verified cases frequently resulted in \nattenuated findings or findings that were no longer statistically significant\n•Remaining statistically significant findings tended to be relatively small in magnitude (i.e., RRs<2)\n•Ischemic stroke cases in the analyses are predominantly occurring in older people and in people in \nthe upper ranges of the age groups studied (e.g., upper range of a 12 –64-year -old age group); \nrelatively few cases are in younger people\nInterpretation of analyses of ischemic stroke and bivalent \nCOVID -19 and influenza vaccination (cont.) \n16▪Available data do not provide clear and consistent evidence of a safety problem for ischemic \nstroke with bivalent mRNA COVID -19 vaccines when given alone or given simultaneously with \ninfluenza vaccines, or when influenza vaccine is given alone\n▪Most study results have not shown an association between vaccination and ischemic stroke, and \nno clear pattern demonstrating increased risk has emerged\n▪Seasonality of stroke risk and an unusual respiratory illness pattern in 2022 -2023 could be \nimpacting the results of some of these analyses; unrecognized SARS -CoV-2 infection could also \nplay a role in occurrence of stroke after vaccination\n▪Any real or theoretical risk needs to be placed in the context of the known benefits of COVID -19 \nand influenza vaccination in preventing COVID -19 and influenza disease and their potentially \nserious complications, including stroke\n▪Simultaneous vaccination provides substantial benefits in keeping patients up -to-date with \nrecommended vaccines and protected from vaccine preventable diseases\n▪Our vaccine safety monitoring systems are designed to be sensitive, and the detection and \nassessment of the ischemic stroke signal and communication to the public is an example of the \nvaccine safety monitoring process working\nNext steps\n17▪Conduct additional analyses on the possible relationship between\nischemic stroke and  bivalent mRNA COVID -19 vaccination,\nsimultaneous administration of bivalent mRNA COVID -19 and\ninfluenza vaccines, and influenza vaccine alone\n▪Continue vigilant safety monitoring of 2023 –2024 COVID -19 and\ninfluenza vaccines, including for ischemic stroke\nAcknowledgements\n18▪CDC Immunization Safety Office\n•VAERS Team\n•Vaccine Safety Datalink (VSD) Team\n•Clinical Immunization Safety Assessment \n(CISA) Project\n▪FDA Center for Biologics Evaluation and \nResearch, Office of Biostatistics and \nPharmacovigilance\n▪Department of Veterans Affairs▪VSD sites\n•Kaiser Permanente Northern California, Oakland, CA\n•Kaiser Permanente Southern California, Los Angeles , CA\n•Marshfield Clinic Research Institute, Marshfield, WI\n•HealthPartners Institute, Minneapolis, MN\n•Kaiser Permanente Colorado, Denver, CO\n•Kaiser Permanente Northwest, Portland, OR\n•Kaiser Permanente Washington, Seattle, WA\n•Denver Health, Denver, CO\n•Harvard Pilgrim Health Care Institute, Boston\nDisclaimer\n▪The findings and conclusions in this presentation are those of the presenter and\ndo not necessarily represent the official position of CDC or FDA\n▪Mention of a product or company name is for identification purposes only and\ndoes not constitute endorsement by CDC or FDA\n19\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the \nofficial position of the Centers for Disease Control and Prevention.\nPhoto credit: James Gathany \n(https://wwwn.cdc.gov/phil/\nDetails.aspx?pid=8876 )", "summary": "National Center for Emerging and Zoonotic Infectious Diseases Update on COVID -19 and influenza vaccine safety Advisory Committee on Immunization Practices (ACIP) meeting October 25, 2023 Tom T. Shimabukuro, MD, MPH, MBA Director, Immunization Safety Office Division of Healthcare Quality Promotion  Centers for Disease Control and Prevention (CDC)  Key points up front 2▪A statistical signal for ischemic stroke after Pfizer -BioNTech bivalent mRNA COVID -19 vaccine was  detected in CDC’s Vaccine…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-25-26-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-10-25-26/01-VaxSafety-Shimabukuro-508.pdf", "doc_date": "2023-10-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 20}
{"title": "01 IZ Schedules Cineas 508", "content": "Centers for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.Recommendations from the Combined Immunization \nSchedule WG for the 2024 Immunization Schedules for Children/Adolescents and Adults \nSybil Cineas, MD, FAAP, FACP (ACIP Combined Immunization WG Chair)\nA. Patricia Wodi, MD (CDC Co -Lead)\nNeil Murthy, MD, MPH, MSJ (CDC Co -Lead)\nACIP Meeting\nOctober 26, 2023\nCombined Immunization Schedules Work Group\nThe Combined Immunization \nSchedule WG updates the \nimmunization schedules annually.\n–Child and adolescent schedule \n(age birth through 18 years)\n–Adult schedule (age 19 years or older)\nThe schedules are primarily \ndesigned to be a tool for healthcare \nproviders to ensure individuals get \nall the vaccines they need when they need them. \n2Immunization Schedules | CDC\nwww.cdc.gov/vaccines/schedules/index.html\n\nThe goal of the Combined Immunization Schedule WG is to better harmonize \nthe child/adolescent and adult schedules.\nNew policies are not established in the  proposed schedules.\n–Annual schedules reflect recommendations already approved by ACIPCombined Immunization Schedules Work Group\n3 \nACIP approval of the proposed schedules is necessary prior to publicationReason Topic is Being Presented to ACIP\nChild/Adolescent Schedule Both Schedules Adult Schedule\n•American Academy of Pediatrics \n(AAP)\n•National Association of Pediatric Nurse Practitioners (NAPNAP)•American Academy of Family \nPhysicians (AAFP)\n•American Academy of Physician \nAssociates (AAPA)\n•American College of Obstetricians and Gynecologists (ACOG)\n•American College of Nurse -\nMidwives (ACNM)•American College of Physicians (ACP)\n•Society for Healthcare Epidemiology of America (SHEA)\n•American Pharmacists Association \n(APhA )\n4\nTraditional Publication Timeline\nOctober November December January February\nACIP vote approves the \nimmunization schedulesProfessional organizations \napprove schedules\nDraft and clear MMWR reports (both \nschedules) and Annals of Internal \nMedicine report (adult schedule only)Publish Schedules (web, app, pdf),\nMMWR Notice to Readers, &\nAnnals of Internal Medicine \nreport published\n5\nInsurance reimbursement\nThe ability of certain health care providers to administer \nimmunizations\n–Some states link pharmacists’ immunization authority to the schedule\nHealth care provider knowledge and practices related to vaccine recommendationsImpacts of Timeliness of Schedule Publication\n6\n2024 immunization schedules: Publication Timeline\nOctober November December January February\nACIP vote approves the \nimmunization schedulesProfessional \norganizations \napprove schedules\n7Publish Schedules\n(web, app, pdf )\nPublish MMWR Notice to \nReaders, &Annals of Internal \nMedicine report published\nACIP Members\nSybil Cineas (ACIP WG Chair)\nVeronica McNally\nMatthew Daley\nLiaison Representatives\nJohn Epling (AAFP) Mary -Margaret Fill (CSTE)\nSarah Coles (AAFP) Chad Rittle (ANA)\nRhoda Sperling (ACOG) William Schafner (NFID)\nHolly Fontenot (SAHM) Robert Hopkins (NFID)\nAmy Middleman (SAHM) Ken Schmader (AGS)\nSandra Fryhofer (ACP/AMA)       Patsy Stinchfield (NAPNAP)Sarah McQueen (AAPA) Preeti Mehrotra (SHEA)\nMarie -Michele Leger (AAPA) Pia Pannaraj (AAP)\nCaitlin Newhouse (AIM)               Kelly Goode ( APhA)Ex Officios\nDavid Kim (OASH)\nSusan Farrall (OASH)\nJane Kim (DVA)\nUzo Chukwuma (IHS)\nConsultants\nHank BernsteinKevin Ault \nPeter Szilagyi\nDiane Peterson\nCarolyn Bridges\nKaren Ketner\nKathleen HarrimanLitjen Tan\nRobert HopkinsSusan LettCombined Immunization Schedule Work Group\n8CDC Co -Leads\nA. Patricia WodiNeil Murthy\nACIP Combined Immunization Work Group —CDC Contributors:\n–Noele Nelson\n–Paul Gastanaduy\n–Samuel Crowe\n–Sarah Kidd\n–Sarah Schillie\n–Susan Goldstein\n–Susan Hariri\n–Suzanne Johnson- DeLeon\n–Tara Anderson\n–Tami Skoff\n–Tatiana LanzieriAcknowledgements\n–Akiko Wilson\n–Andrew Kroger\n–Amadea Britton \n–David Sugerman \n–Donna Williams\n–Erin Conners\n–Hilda Razzaghi\n–Holly Hill\n–Jacqueline Tate\n–Janell Routh\n–Jefferson Jones \n–Jennifer Collins–JoEllen Wolicki\n–Katherine Fleming -Dutra\n–Lakshmi Panagiotakopoulos\n–Lauri Markowitz\n–Lisa Grohskopf\n–Lucy McNamara\n–Mary Chamberland\n–Megan Wallace\n–Michael Melgar \n–Michelle Hughes\n–Miwako Kobayashi\n–Mona Marin\n9\nThe use of vaccine trade names is for identification purposes only and \ndoes not imply endorsement by the Centers for Disease Control and \nPrevention.\nThe 2024 schedules presented in the following slides are drafts and are \ntherefore subject to change based on ACIP’s discussion and vote.Disclaimer\n10\nHarmonization between the child/adolescent and adult schedules\nEdits to all tables\nContent changes of the notes\nContent changes to the appendix listing contraindications and precautions\nDiscussion and VoteOutline\n11", "summary": "Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-25-26-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-10-25-26/01-IZ-Schedules-Cineas-508.pdf", "doc_date": "2023-10-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 11}
{"title": "02 IZ Schedules Wodi 508", "content": "\u0000\n\u0001\n\u0002\n\u0003\n\u0002\u0004\u0005\u0006\u0007\n\u0001 \b\n\u0006\t\n\n \u000b\n\f\u0006\u0004\r\b\n\u000b\n\t\u000e\n\u000f \u0010\n\r\n\n\u000b\n\t\n\u0003\n\u0001\u000b\n\b\u0007\u0005\r\b\r\t\n\u0003\n\u0006\n\u0003\u000b\n\u0002\t\u0006\u0005\r\n\u000f\u000b\n\u000e\r\t \b\r\n\n\b\u0002\n\u000f\n\r\n\u000f \u0011\u0012\n\u0002\u0005\n\u0013\u0014\u0013\n\u0015 \u0016\n\u0013\u0017\u0018\u0014\n\u0002\t\n\u000f\u000b\n\t\r\u0006\t\n\n\u0007\u0005\r\b\r\t\n\u0003\n\u0006\n\u0003\u000b\n\u0002\t\u0010\b\r \u0019\n\u0016\n\u0002\u0005\u000b\n\u0004\n\u0001\n\u0003\b\u0006\u0005\r\u000b\n\f\u0007\n\u000f\u000b\n\r\n\n\u0002\u0005\r\u001a\n\u0003\n\r\t\n\n\r\n\n\u0012\n\u0002\u0005\u0010\b\r\u000b\n\t\u0007\u0005\u000b\n\t\n\u0003\u000b\n\t\u0004\u0002\u0005\u0006\t \u0011\u0010\b\r\n\u001b\u0011\u0002\n\u0003\n\u0001\n\r\u0005\n\u0013\u0014\u0013\u0013\u0017\u001c\b\u0002\u0005\u0006\t \u0011\r\u001a\n\u0003\n\r\u0005\t\u0006\n\u000f\n\u0006\u0010\n\n\u000b\n\r\t\u000e\r\b\n\u0019\nƒ\nƒ\nƒ\nƒƒ\nƒ\nƒ\nƒ\nƒ\nƒ\nƒ\nƒ\nƒ\nƒ\nƒƒ\nƒ\nƒ\nƒ\nƒ\nƒ\nƒ\n\u001d\n\u001e\n\u001f\nƒ\nƒ\n\n !\n\"#$%#&\n'\n$\n()*\n+\n$\n,\n!\"-\n. !\n/ 0\n$\"#!1!\"!\n/\n0\n2 3\n34%$5$36\"$3\n2\n#!\n,\n7\n4\n.\n/2\n%!#1-55\n2\n%-\n.\n2\n$%#!\"\n2\n!#\n80-9 !9\"$46-%\n,\n%4 3\n8\n!\"$\n:\n6\"!1\n2\n$4#;7<=> ?\n@A,\n$#!#\nB C\nDEFGE\nHIJ\nKF\nL\nCDM\nN C\nO PFDECQCDC\nO PR\nKKSGFTFKUDFK\nR\nEC\nL\nV\nS\nN\nO\nR\nGCEQMTT\nR\nGM\nN\nR\nFGECD\nR\nCE\nWPMX CXDFSUMG\nLGSK\nW\nCDF\nY\nUDCQ\nR\nFSE\nZV[\\] ^\n_`\nL\nFECE\na\nFQC\nLR\nG\nY\nFDKM\nN\nR\nFGFGK\nR\nG\nR\nKM\nOL\nFECEW\nC\nN b\nCCG\naac[\nN\nFT\nO\nMD\nR\nYP\nN\nd\nR\nEM\nO\nEFMUU\nO\nR\nCE\nN\nF\ne\nUCT\nR\nM\nOE\nR\nN\nSM\nN\nR\nFGE f\ng\nLL\nC\nL\nN\nd\nC\nY\nF\nOO\nFb\nR\nGXKC\nL\nR\nTM\nO\nTFG\nL\nR\nN\nR\nFGE\nZ\nd\nDFG\nR\nT\nh\nR\nL\nGCP\nL\nR\nECMEC\ni\nCjT\nO\nS\nL\nR\nGXKM\nR\nG\nN C\nGMGT C\nL\nR\nM\nO PE\nR\nEMG\nLGCU\nd\nDF\nN\nR\nTEPG\nL\nDFKC\nk\nZ\nd\nDFG\nR\nT\nO\nR\nQCD\nL\nR\nECMEC\nZ\nd\nDFG\nR\nT\nO\nSGX\nL\nR\nECMEC\ni\nR\nGT\nO\nS\nL\nR\nGXKF\nL\nCDM\nN C\nUCDE\nR\nE\nN C\nG\nN\nFDECQCDC\nUCDE\nR\nE\nN\nCG\nN\nME\nN\nd\nKM\nk\ng\nLL\nC\nL\nR\nG\nY\nFDKM\nN\nR\nFG\nY\nFDUCDEFGEMX C\n_l\nPCMDE\nh\nGFbGFDESEUCT\nN C\nL\nN\nF\nW\nCSGQMTT\nR\nGM\nN\nC\nL\nFDR\nGTFKU\nO\nC\nN C\nO PQMTT\nR\nGM\nN C\nL m\nc C\nQ\nR\nEC\nL\nN\nF\nR\nGT\nO\nS\nL\nCDCTFKKCG\nL\nM\nN\nR\nFGEY\nFDUCDEFGEMX C\n_l\nPCMDEM\nN\nR\nGTDCMEC\nLD\nR\nE\nh\nF\nY\nCjUFESDC\nN\nFUF\nO\nR\nFQ\nR\nDSEMG\nLd\nMQCTFKU\nO\nC\nN C\nL\nN\nd\nCUD\nR\nKMDPECD\nR\nCE f\nn,,\n!\n,\n%$\n.\n!$%\n.\n2 32\n%9$\n:%\n2\n\"#!1\n2 3\n-\n8\n-\n, 32\n%\n2\n#\n.\n\"-\n.\n2\n$% o\nn,,\n!\n,\n%$\n.\n!$%4#!$\n:\n%\n2\n\"#!1\n2 3\n-\n82\n%5\n'2/,\n\"!%&\n'\n$\n'\n-1!\"!5!\n2\n1!\n,6-\n/2\n1\n2 p\n4 3-\n8o\nn,,\n!\n,/2\n%\nq\n.\n$%\n2\n\"#!1\n2 3\n-\n8:\n\"!r4!%\n.\n/\n0-#\nq!\n,\nr4!#\n.\n2\n$%#& !\n8\n6-9!\ns\nFDKFDC\nR\nG\nY\nFDKM\nN\nR\nFG t\nTFG\nN\nMT\nN\nZ]Z_\n^\nluu^\nZ]Z^\n\\vsV\ni w\nx w\n^\ny\u001ex\u001e\nkzz{ |\n_ ^\nlll^\nwxw\n^\n\u001exyl\nbbb\nf\nT\nL\nTf\nXFQz\nd\nC\nY\nR\nG\nL\nR\nGXEMG\nL\nTFGT\nO\nSE\nR\nFGE\nR\nG\nN\nd\nR\nEDCUFD\nN\nMDC\nN\nd\nFECF\nY\nN\nd\nCMS\nN\nd\nFDEMG\nLL\nFGF\nN\nGCT CEEMD\nR\nOPDCUDCECG\nNN\nd\nCF\nYY\nR\nT\nR\nM\nO\nUFE\nR\nN\nR\nFGF\nY\nN\nd\nC\nZ C\nG\nN C\nDE\nY\nFD\n]R\nECMEC\nZ\nFG\nN\nDF\nO\nMG\nL\nB\nDCQCG\nN\nR\nFG\nf", "summary": "\u0000 \u0001 \u0002 \u0003 \u0002\u0004\u0005\u0006\u0007 \u0001 \b \u0006\t   \u000b \f\u0006\u0004\r\b \u000b \t\u000e \u000f \u0010 \r  \u000b \t \u0003 \u0001\u000b \b\u0007\u0005\r\b\r\t \u0003 \u0006 \u0003\u000b \u0002\t\u0006\u0005\r \u000f\u000b \u000e\r\t \b\r  \b\u0002 \u000f \r \u000f \u0011\u0012 \u0002\u0005 \u0013\u0014\u0013 \u0015 \u0016 \u0013\u0017\u0018\u0014 \u0002\t \u000f\u000b \t\r\u0006\t  \u0007\u0005\r\b\r\t \u0003 \u0006 \u0003\u000b \u0002\t\u0010\b\r \u0019 \u0016 \u0002\u0005\u000b \u0004 \u0001 \u0003\b\u0006\u0005\r\u000b \f\u0007 \u000f\u000b \r  \u0002\u0005\r\u001a \u0003 \r\t  \r  \u0012 \u0002\u0005\u0010\b\r\u000b \t\u0007\u0005\u000b \t \u0003\u000b \t\u0004\u0002\u0005\u0006\t \u0011\u0010\b\r \u001b\u0011\u0002 \u0003 \u0001 \r\u0005 \u0013\u0014\u0013\u0013\u0017\u001c\b\u0002\u0005\u0006\t \u0011\r\u001a \u0003 \r\u0005\t\u0006 \u000f \u0006\u0010  \u000b \r\t\u000e\r\b \u0019 ƒ ƒ ƒ ƒƒ ƒ ƒ ƒ ƒ ƒ ƒ ƒ ƒ ƒ ƒƒ ƒ ƒ ƒ ƒ ƒ ƒ \u001d \u001e \u001f ƒ ƒ   ! \"#$%#& ' $ ()* + $ , !\"- . ! / 0 $\"#!1!\"! / 0 2 3 34%$5$36\"$3 2 #! , 7 4 . /2 %!#1-55 2 %- . 2 $%#!\" 2 !# 80-9 !9\"$46-% , %4 3 8 !\"$ : 6\"!1 2 $4#;7<=> ? @A, $#!# B C DEFGE HIJ…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-25-26-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-10-25-26/02-IZ-Schedules-Wodi-508.pdf", "doc_date": "2023-10-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 61}
{"title": "03 IZ Schedules Murthy 508", "content": "ƒ\nƒ\nƒƒ\nƒ\nƒ\nƒ\nƒ\nƒ\nƒ\nƒ\nƒ\nƒ\nƒ\nƒƒ\nƒ\nƒ\nƒ\nƒ\nƒ\nƒ\nƒ\n\n\u0000 \u0001\n\u0001\n\u0002 \u0003\u0004 \u0001\n\u0005\n\u0000 \u0001\n\u0001\n\u0002 \u0003\u0004 \u0001\n\u0005\n\u0000 \u0001\n\u0001\n\u0002 \u0003\u0004 \u0001\n\u0005\n\u0000 \u0001\n\u0001\n\u0002 \u0003\u0004 \u0001\n\u0005\n\u0006 \u0007\n\b\t\n\u000b\t\n\f\r\u000e\n\u000f\n\u0010\n\u0007\b\u0011\n\u0012 \u0007\n\u0013 \u0014\u0015\n\t\u0007\u0016\u0007\b\u0007\n\u0013 \u0014\n\u0017\n\u000f\u000f\u0018\u000b\n\u0019\n\u000f\u001a\b\n\u000f\n\u0017\n\t\u0007\n\u0010\u001b\n\u001c\n\u0018\n\u0012\n\u0013\n\u0017\n\u000b\u0007\t\u0016\u0011\u0019\u0019\n\u0017\n\u000b\u0011\n\u0012\u0017\n\n\u000b\t\u0007\b\n\u0017\n\u0007\t\n\u001d\u0014\u001a\b\u0007\u0016\n\u0017\n\n\u0018\t\n\u001e\u001c\u001f ! \"\n#$\u0016\u0011\u0019\u0019\n\u0017\n\u000b\u0011\n\u0012\u0017\n\n\u000b\n%\n\u0017\n\t\n\u0012\n\n\b\u0014 &\n\u0006 \u0007\n\b\t\n\u000b\t'\n%\n\n()*\n\u000f\n\u0010\n\u0007\b\u0011\n\u0012\n\u0007\n\u0013 \u0014\u0015\n\t\u0007\u0016\u0007\b\u0007\n\u0013 \u0014\n\u0017\n\u000f\u000f\u0018\u000b\n\u0019\n\u000f\u001a\b\n\u000f\n\u0017\n\t\u0007\n\u0010\u001b\n\u001c\n\u0018\n\u0012\n\u0013\n\u0017\n\u000b\u0007\t\u0016\u0011\u0019\u0019\n\u0017\n\u000b\u0011\n\u0012\u0017\n\n\u000b\t\u0007\b\n\u0017\n\u0007\t\n\u001d\u0014\u001a\b\u0007\u0016\n\u0017\n\n\u0018\t\n\u001e\u001c\u001f ! \"\n#$\u0016\u0011\u0019\u0019\n\u0017\n\u000b\u0011\n\u0012\u0017\n\n\u000b\n%\n\u0017\n\t\n\u0012\n\n\b\u0014&\n+\n, -\n. /\n0\n1 2\n34\n5 6\n78\n9 :4;<<\n5 =\n;\n>\n3\n?\n5\n8\n?\n3\n@\n5 =\n3\n?\n;8\nA\n;4\n5=B23<3\n5\n43\n?\n; =:\nC 25\nB\n5=;\n9\nD6=64;\n9\n3=\n>\n62\nE\n5\n4;\n9\n3=\n>FCGHI J\nKL\n4;<<\n5 =\n3\nM N\n; =883= O\nP\n6\n?\n3 2=;O\nQ\n64;4;RO1\n@\n5 S\n3 2\nJ\nT5\n6\nQU\n3<\nAV W2\n5 6\n2\n>6\n>\nA\n37W\n?\n;\n>\n3\n? X\nYXZ [\nXYX\\@62D7\n9\n;\n>\n5\n6= ]\nx\n^\n??\n3\n?\n=3_\nE\n7\n99\n3\n>\nx\n`62D 623\n5 =\n@62D;\n>\n5\n6= O\n<6=\n>\n;<\n>\nFIFK\nJ\naYYJ\nFIFJ\nHQ`C\nMXZX\nJ\n\\bZb\nVUUc d\nK\nJ\naaa J\nXZX\nJ\nbZ\\a\n___]\n<\n?\n<]\nB64U\nA\n3\n@\n5=\n?\n5=B8; =\n?\n<6=<\n9\n78\n5\n6=8\n5 =\n>\nA\n5\n823W62\n>\n;23\n>\nA\n6836\n@\n>\nA\n3;7\n>\nA\n628;=\n?? 6=6\n>\n=3<388;2\n5\n9 :23W2383=\n>>\nA\n36\n@@\n5\n<\n5\n;\n9W68\n5\n>\n5\n6=6\n@\n>\nA\n3\nF\n3=\n>\n328\n@62\nI5\n83;83\nF6=\n>26\n9\n;=\n?\n1 2\n343=\n>\n5 6\n= ]", "summary": "ƒ ƒ ƒƒ ƒ ƒ ƒ ƒ ƒ ƒ ƒ ƒ ƒ ƒ ƒƒ ƒ ƒ ƒ ƒ ƒ ƒ ƒ  \u0000 \u0001 \u0001 \u0002 \u0003\u0004 \u0001 \u0005 \u0000 \u0001 \u0001 \u0002 \u0003\u0004 \u0001 \u0005 \u0000 \u0001 \u0001 \u0002 \u0003\u0004 \u0001 \u0005 \u0000 \u0001 \u0001 \u0002 \u0003\u0004 \u0001 \u0005 \u0006 \u0007 \b\t \u000b\t \f\r\u000e \u000f \u0010 \u0007\b\u0011 \u0012 \u0007 \u0013 \u0014\u0015 \t\u0007\u0016\u0007\b\u0007 \u0013 \u0014 \u0017 \u000f\u000f\u0018\u000b \u0019 \u000f\u001a\b \u000f \u0017 \t\u0007 \u0010\u001b \u001c \u0018 \u0012 \u0013 \u0017 \u000b\u0007\t\u0016\u0011\u0019\u0019 \u0017 \u000b\u0011 \u0012\u0017  \u000b\t\u0007\b \u0017 \u0007\t \u001d\u0014\u001a\b\u0007\u0016 \u0017  \u0018\t \u001e\u001c\u001f ! \" #$\u0016\u0011\u0019\u0019 \u0017 \u000b\u0011 \u0012\u0017  \u000b % \u0017 \t \u0012  \b\u0014 & \u0006 \u0007 \b\t \u000b\t' %  ()* \u000f \u0010 \u0007\b\u0011 \u0012 \u0007 \u0013 \u0014\u0015 \t\u0007\u0016\u0007\b\u0007 \u0013 \u0014 \u0017 \u000f\u000f\u0018\u000b \u0019 \u000f\u001a\b \u000f \u0017 \t\u0007 \u0010\u001b \u001c \u0018 \u0012 \u0013 \u0017 \u000b\u0007\t\u0016\u0011\u0019\u0019 \u0017 \u000b\u0011 \u0012\u0017  \u000b\t\u0007\b \u0017 \u0007\t \u001d\u0014\u001a\b\u0007\u0016 \u0017  \u0018\t \u001e\u001c\u001f ! \" #$\u0016\u0011\u0019\u0019 \u0017 \u000b\u0011 \u0012\u0017  \u000b % \u0017 \t \u0012  \b\u0014& + , - . / 0 1 2 34 5 6 78 9 :4;<< 5 = ; > 3 ? 5 8 ? 3 @ 5 = 3 ? ;8 A ;4 5=B23<3…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-25-26-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-10-25-26/03-IZ-Schedules-Murthy-508.pdf", "doc_date": "2023-10-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 50}
{"title": "01 Chikungunya Bell 508", "content": "CHIKUNGUNYA VACCINES\nBeth Bell, MD, MPH\nChair, ACIP Chikungunya Vaccines Work GroupACIP Meeting\nOctober 26, 2023\nBackground\nExpected licensure date for Valneva’s chikungunya vaccine revised from \nAugust 2023 to November 2023\nNo chikungunya vaccine ever licensed in United States or globally\nNo existing ACIP chikungunya vaccine recommendations\nChikungunya Vaccines Work Group is developing policy options for ACIP’s consideration for use of chikungunya vaccine among U.S. persons at risk of \nchikungunya, including \n–Travelers\n–Laboratory workers\n–Residents of U.S. territories and states with, or at risk of, transmission\nRecap of previous Work Group presentations to ACIP \nOctober 2022\n–Overview of chikungunya virus disease and vaccines\n–Immunogenicity and safety of Valneva’s chikungunya vaccine\nFebruary 2023\n–Global epidemiology of chikungunya\n–Chikungunya among U.S. travelers\n–Persistent arthralgia following chikungunya\nJune 2023\n–Value of a vaccine to U.S. travelers\n–Chikungunya virus infection among laboratory workers\n–Observations on a large chikungunya outbreak in Paraguay\nOverview of today’s session\nEvidence to Recommendations for chikungunya vaccine use among U.S. \ntravelers*\n–Dr. Susan Hills (CDC/NCEZID)\nEvidence to Recommendations for chikungunya vaccine use among \nlaboratory workers*\n–Dr. Susan Hills (CDC/NCEZID)\n*Anticipated vote at February 2024 ACIP meeting if vaccine is licensed\nACIP Ex Officio Invited Consultants\nBeth Bell, Univ Washington (Chair) Robin Levis, FDA Alan Barrett, Univ Texas Galveston\nWilbur Chen, Univ Maryland Sixun Yang, FDA Carina Blackmore, Florida Dept Health\nLesley Dupuy, NIH Alan Lam, DoD\nCDC Leads Margaret Ryan, DoD\nSusan Hills, DVBD (Lead) ACIP Liaisons Steven Schofield, CATMAT\nNicole Lindsey, DVBD (Deputy Lead) Elizabeth Barnett, ISTM David Shlim, Jackson Hole Travel & Trop Med\nJames Campbell, AAP Nestor Sosa, Uni New Mexico Hospital\nMary Pat Friedlander, AAFP Sanet Torres, San Jorge Children & Women's Hospital\nSaroj Rai, AIM Kirsten Vannice, Bill & Melinda Gates Foundation\nMary Wilson, Univ California San FranciscoChikungunya Vaccines Work Group members\nDVBD DGMQ ISD\nErin Staples Sarah Guagliardo Elisabeth Velazque z\nAnn Powers\nLaura Adams DHQP GRADE/ETR consultants\nJoshua Wong Michael McNeil Doug Campos -Outcalt\nRebecca Morgan\nNCEZID GID\nRita Helfand Rebecca Casey ACIP Secretariat\nJessica MacNeil, NCIRD\nLeslie Lee, NCIRDChikungunya Vaccines Work Group CDC participants", "summary": "CHIKUNGUNYA VACCINES Beth Bell, MD, MPH Chair, ACIP Chikungunya Vaccines Work GroupACIP Meeting October 26, 2023 Background Expected licensure date for Valneva’s chikungunya vaccine revised from  August 2023 to November 2023 No chikungunya vaccine ever licensed in United States or globally No existing ACIP chikungunya vaccine recommendations Chikungunya Vaccines Work Group is developing policy options for ACIP’s consideration for use of chikungunya vaccine among U.S. persons at risk of …", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-25-26-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-10-25-26/01-Chikungunya-Bell-508.pdf", "doc_date": "2023-10-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 6}
{"title": "02 Chikungunya Hills 508", "content": "National Center for Emerging and Zoonotic Infectious Diseases\nEVIDENCE TO RECOMMENDATIONS FOR \nCHIKUNGUNYA VACCINE USE AMONG \nADULT TRAVELERS\nSusan Hills, MBBS, MTH\nCDC Lead , Chikungunya Vaccines Work Group\nArboviral Diseases Branch\nDivision of Vector -Borne Diseases\nFort Collins, Colorado\nACIP meeting, October 26, 2023\nChikungunya virus and transmission\nAlphavirus \nPrimarily transmitted by Aedes \naegypti and Aedes albopictus\nUncommon modes of \ntransmission\n–Laboratory exposure\n–Intrauterine and intrapartum\n–Bloodborne transmission \nthrough needlestick\n\nDistribution\nTropical and subtropical \nregions\nLarge outbreaks have occurred in most parts of \nthe world\n–Often high attack ratesCountries and territories with current or past transmission \nof chikungunya virus\nhttps://www.cdc.gov/chikungunya/geo/index.html\n\nClinical features of acute chikungunya virus infection\nFebrile illness with arthralgia which is often severe and debilitating  \nRare serious complications (e.g., neurologic illness, myocarditis, hepatic or \nrenal disease)\nNo anti -viral treatment\n\nRisk factors for severe disease \nAge >65 years \nAge <1 year\nUnderlying medical conditions \n(e.g., diabetes, heart disease, \nhypertension)\nIntrapartum transmission \n\nChikungunya vaccine\nLive attenuated vaccine manufactured by Valneva\nSingle dose primary schedule\nInitial licensure for adults aged ≥18 years\nCurrently under consideration by US Food & Drug Administration\nNot yet licensed anywhere in world\nNo existing vaccine recommendations from ACIP or other vaccine \nadvisory groups \nEvidence to Recommendations for \nchikungunya vaccination for travelers \nPolicy question\nShould chikungunya vaccine be recommended for use in \npersons aged ≥18 years traveling to areas with risk of \nchikungunya virus transmission? \nDomain 1. Public health problem\nIs chikungunya of public health importance?\nHundreds of thousands of cases \nreported annually \nRisk highly variable for US travelers\n100– 200 reported cases annually \nHundreds of thousands of cases \nreported annually \nRisk highly variable for US travelers\n100– 200 reported cases annually \nHundreds of thousands of cases \nreported annually \n\nRisk highly variable for US travelers\n100– 200 reported cases annually \nHundreds of thousands of cases \nreported annually \nMortality <1%\n\nPublic health problem\nIs chikungunya of public health importance?\noNo oProbably no oProbably yes oYes oVaries oDon’t know\nDomain 2: Benefits and harms of chikungunya \nvaccine\nHow substantial are the desirable anticipated effects?\nShort -term and long -term protection from disease\nNo efficacy data so i mmunogenicity data reviewed\n–No correlate of protection\nLicensure through Accelerated Approval pathway\n–Effectiveness demonstrated by clinical trials showing vaccine has effect on \nsurrogate endpoint reasonably likely to predict clinical benefit\n–Vaccine effectiveness will need to be confirmed in post -licensure field studies\nMarker of protection based on neutralizing antibody titer estimated from \nvalidated non- human primate model\nSeroresponse at 28 days after vaccination\nTwo studies \n–One randomized controlled trial\n–One lot -to-lot consistency study with no placebo group \nTotal of 622 subjects\nSeroresponse at 28 days: ≥98% \nNone of 96 subjects in placebo arm of randomized controlled trial \nhad  seroresponse\nSeroresponse at 12 months after vaccination\nOne study with 360 subjects\nSeroresponse at 12 months: 99% \nHow substantial are the desirable anticipated effects?\noMinimal oSmall oModerate oLarge oVaries oDon’t know\nHow substantial are the undesirable anticipated effects?\nSerious adverse events (SAE) within 6 months\nSAE\n–51 (1.5% ) of 3,490 vaccinated subjects in 2 trials reported SAE\n–8 (0.8% ) of 1,033 placebo recipients in randomized controlled trial reported SAE*\nRelated SAEs \n–2 events ( 0.1% ) considered vaccine -related by study investigators\n•Hospitalization for severe myalgia\n•Hospitalization for myalgia, high fever, syndrome of inappropriate antidiuretic \nhormone excretion, and atrial fibrillation\n*No significant difference from vaccine group; 46 (1.5%) of 3,082 vaccinated subjects in randomized, controlled trial\nArthralgia and arthritis in randomized controlled trial*\nVaccinated group \n(N=3082)Placebo group\n(N=1033)\nn(%) n(%) Risk ratio (95% CI)\nAny arthralgia within 10 days#520 (17%) 50 (5%) 3.5 (2.6, 4.6)¥\nSevere arthralgia within 10 days#,€9(0.3%) 0(0%) 6.0 (0.4, 104.2)\nPersistent arthralgia≠9(0.3%) 4(0.4%) 0.8 (0.2, 2.4)\nArthritis within 6 months£5(0.2%) 2(0.2%) 0.8 (0.2, 4.3)\nNew onset or worsening osteoarthritis \nwithin 6 months£12 (0.4%) 2(0.2%) 2(0.5, 9.0)\n#Solicited adverse event ; ¥Significant difference; €Severe arthralgia defined as an event that prevented daily activity; \n≠Commencing within 10 days and with duration >15 days; £Unsolicited adverse event\n*Similar percentage of events in vaccinated subjects in lot -to-lot consistency study (N=408) without placebo control group\nArthralgia and arthritis in randomized controlled trial\nVaccinated group \n(N=3082)Placebo group\n(N=1033)\nn(%) n(%) Risk ratio (95% CI)\nAny arthralgia within 10 days#520 (17%) 50 (5%) 3.5 (2.6, 4.6)¥\nSevere arthralgia within 10 days#,€9(0.3%) 0(0%) 6.0 (0.4, 104.2)\nPersistent arthralgia≠9(0.3%) 4(0.4%) 0.8 (0.2, 2.4)\nArthritis within 6 months£5(0.2%) 2(0.2%) 0.8 (0.2, 4.3)\nNew onset or worsening osteoarthritis \nwithin 6 months£12 (0.4%) 2(0.2%) 2(0.5, 9.0)\n#Solicited adverse event ; ¥Significant difference; €Severe arthralgia defined as an event that prevented daily activity; \n≠Commencing within 10 days and with duration >15 days; £Unsolicited adverse event\nArthralgia and arthritis in randomized controlled trial\nVaccinated group \n(N=3082)Placebo group\n(N=1033)\nn(%) n(%) Risk ratio (95% CI)\nAny arthralgia within 10 days#520 (17%) 50 (5%) 3.5 (2.6, 4.6)¥\nSevere arthralgia within 10 days#,€9(0.3%) 0(0%) 6.0 (0.4, 104.2)\nPersistent arthralgia≠9(0.3%) 4(0.4%) 0.8 (0.2, 2.4)\nArthritis within 6 months£5(0.2%) 2(0.2%) 0.8 (0.2, 4.3)\nNew onset or worsening osteoarthritis \nwithin 6 months£12 (0.4%) 2(0.2%) 2(0.5, 9.0)\n#Solicited adverse event ; ¥Significant difference; €Severe arthralgia defined as an event that prevented daily activity; \n≠Commencing within 10 days and with duration >15 days; £Unsolicited adverse event\nArthralgia and arthritis in randomized controlled trial\nVaccinated group \n(N=3082)Placebo group\n(N=1033)\nn(%) n(%) Risk ratio (95% CI)\nAny arthralgia within 10 days#520 (17%) 50 (5%) 3.5 (2.6, 4.6)¥\nSevere arthralgia within 10 days#,€9(0.3%) 0(0%) 6.0 (0.4, 104.2)\nPersistent arthralgia≠9(0.3%) 4(0.4%) 0.8 (0.2, 2.4)\nArthritis within 6 months£5(0.2%) 2(0.2%) 0.8 (0.2, 4.3)\nNew onset or worsening osteoarthritis \nwithin 6 months£12 (0.4%) 2(0.2%) 2(0.5, 9.0)\n#Solicited adverse event ; ¥Significant difference; €Severe arthralgia defined as an event that prevented daily activity; \n≠Commencing within 10 days and with duration >15 days; £Unsolicited adverse event\nArthralgia and arthritis in randomized controlled trial\nVaccinated group \n(N=3082)Placebo group\n(N=1033)\nn(%) n(%) Risk ratio (95% CI)\nAny arthralgia within 10 days#520 (17%) 50 (5%) 3.5 (2.6, 4.6)¥\nSevere arthralgia within 10 days#,€9(0.3%) 0(0%) 6.0 (0.4, 104.2)\nPersistent arthralgia≠9(0.3%) 4(0.4%) 0.8 (0.2, 2.4)\nArthritis within 6 months£5(0.2%) 2(0.2%) 0.8 (0.2, 4.3)\nNew onset or worsening osteoarthritis \nwithin 6 months£12 (0.4%) 2(0.2%) 2(0.5, 9.0)\n#Solicited adverse event ; ¥Significant difference; €Severe arthralgia defined as an event that prevented daily activity; \n≠Commencing within 10 days and with duration >15 days; £Unsolicited adverse event\nArthralgia and arthritis in randomized controlled trial\nVaccinated group \n(N=3082)Placebo group\n(N=1033)\nn(%) n(%) Risk ratio (95% CI)\nAny arthralgia within 10 days#520 (17%) 50 (5%) 3.5 (2.6, 4.6)¥\nSevere arthralgia within 10 days#,€9(0.3%) 0(0%) 6.0 (0.4, 104.2)\nPersistent arthralgia≠9(0.3%) 4(0.4%) 0.8 (0.2, 2.4)\nArthritis within 6 months£5(0.2%) 2(0.2%) 0.8 (0.2, 4.3)\nNew onset or worsening osteoarthritis \nwithin 6 months£12 (0.4%) 2(0.2%) 2(0.5, 9.0)\n#Solicited adverse event ; ¥Significant difference; €Severe arthralgia defined as an event that prevented daily activity; \n≠Commencing within 10 days and with duration >15 days; £Unsolicited adverse event\nHow substantial are the undesirable anticipated effects?\noMinimal oSmall oModerate oLarge oVaries oDon’t know\nDo the desirable effects outweigh the undesirable effects?\nBalance of desirable and undesirable effects\nHigh seroresponse rates through at least 1 year after vaccination\nNo serious safety concerns identified in trials performed to date\nPrevents disease that can result in severe arthralgia during acute illness, \nrare serious complications, and sometimes long -term arthralgia \nHealthcare provider should discuss desirable and undesirable effects of vaccination and individual risk based on disease risk at destination, \nactivities, and personal factors \n–For some travelers, even low probability of SAE might be higher than disease risk \n–Target vaccine to travelers at higher risk for disease\nDo the desirable effects outweigh the undesirable effects?\noFavors \nintervention oFavors \ncomparisonoFavors \nbothoFavors \nneitheroVariesoDon’t \nknow\nWhat is the overall certainty of the evidence for the \ncritical outcomes?\nWhat is the overall certainty of the evidence for \nprotection from chikungunya ?\noNo studies found oVery low oLow oModerate oHigh\nNo vaccine efficacy data, no immunologic correlate of protection, \nprotection based on surrogate endpoint reasonably likely to predict \nclinical benefit and requiring confirmation by post -licensure vaccine \neffectiveness studies\nWhat is the overall certainty of the evidence for \nsafety of chikungunya vaccination ?\noNo studies found oVery low oLow oModerate oHigh\nNumber of subjects in trials insufficient to detect rare adverse events, \nconfidence intervals indicated potential for benefit or harm, and/or \nsuboptimal method for collection of specific outcome information \nDomain 3. Values\nDoes the target population feel that the desirable \neffects are large relative to undesirable effects?\nIs there important uncertainty about or variability \nin how much people value the main outcomes?\nPerceptions among US adults aged ≥18 years of the \nvalue of a chikungunya vaccine (CDC study) \nOnline survey conducted in 2022 \nParticipants provided information on \n–Risk for disease with travel during outbreak or non -outbreak \nperiods\n–Rates of chronic arthralgia after chikungunya\n–Vaccine cost \nResults \n42%\n26%32%\nLikely* Unsure Unlikely**\n*Includes very and somewhat likely responses\n**Includes very and somewhat unlikely responsesOutbreak period (risk of 1 in 150) Non -outbreak period (risk of 1 in 15,000)\n27%\n24%49%\nLikely* Unsure Unlikely**N=4,146N=4,138\nVariability in responses \nLower likelihood of vaccination\n–Persons aged 18 –29 years\n–Lower education\n–Lower household income\n–Black race\nImportant factors in decision -making\nRisk of disease\nVaccine side effects Avoid risk of long -term joint pain Vaccine cost\nPerceptions among US adults aged ≥18 years of value of \nchikungunya vaccine (Valneva study) \nOnline survey conducted in 2021 \n2,002 US residents who had traveled internationally during last 3 \nyears or planned to do so within next 3 years\nLimited information about participants provided but anyone who self-identified as ‘anti -vaccination’ excluded \nResults\nAfter being provided basic information on chikungunya \nand its sequelae\n–72% were very or somewhat likely to ask healthcare provider \nabout a vaccine\n–81% were very or somewhat likely to be vaccinated if \nrecommended by healthcare provider\nValues\nDoes the target population feel that the desirable \neffects are large relative to undesirable effects?\noNo oProbably no oProbably yes oYes oVaries oDon’t know\nValues\nIs there important uncertainty about or variability \nin how much people value the main outcomes?\noImportant \nuncertainty \nor variabilityoProbably important \nuncertainty or variabilityoProbably not important uncertainty or variabilityoNo important \nuncertainty or \nvariabilityoNo known undesirable outcomes\nDomain 4. Acceptability\nIs chikungunya vaccine acceptable to key stakeholders?\nAcceptability to key stakeholders\nTravel medicine and other healthcare providers\n–Online survey in 2021 (Valneva) among 158 US healthcare \nproviders who routinely provide travel health services \nindicated 87% were very or somewhat likely to \nrecommend vaccine if recommended by ACIP\nTravelers\n–Option for protection from a disease that can cause \nsevere arthralgia and potentially long -term joint pain\nAcceptability\nIs the intervention acceptable to key stakeholders?\noNo oProbably no oProbably yes oYes oVaries oDon’t know\nDomain 5. Resource use\nIs chikungunya vaccination a reasonable and efficient \nallocation of resources?\nCost -effectiveness considerations\nNo cost- effectiveness analysis (CEA)\n–Most travel vaccines are not cost -effective\n–Chikungunya vaccine for travelers is not likely to be cost -effective \nCEA less relevant for travel vaccine\n–Decision is for individual traveler and not for population\n–Vaccine paid for by traveler and generally not covered by insurance \nVaccine recommendations targeting higher risk travelers probably reasonable \nallocation of resources\n–Financial implications borne by travelers most at risk and who benefit most\nResource use\nIs chikungunya vaccination a reasonable and \nefficient allocation of resources?\noNo oProbably no oProbably yes oYes oVaries oDon’t know\nDomain 6. Equity\nWhat would be the impact on health equity?\nHealth equity considerations\nVaccine primarily paid for out of pocket\n–Some travelers not have resources to pay for vaccine\nTravel medicine providers likely have better awareness of disease and \nvaccine availability than non- specialist providers\n–People with fewer resources less likely to attend travel medicine provider\nChikungunya vaccine recommendations cannot address these issues\nEquity\nWhat would be the impact on health equity?\noReducedoProbably \nreducedoProbably \nno impactoProbably increasedoIncreased oVariesoDon’t know\nDomain 7. Feasibility\nIs the intervention feasible to implement?\nFeasibility considerations\nSingle dose primary series allows administration in pre -travel \nconsultation\nDisease risk highest, and vaccination most of benefit, during \noutbreaks\n–Challenge with delay in awareness of outbreaks\n–CDC will post information on website once aware of outbreaks\nFeasibility\nIs the intervention feasible to implement?\noNo oProbably no oProbably yes oYes oVaries oDon’t know\nBalance of consequences\no Undesirable \nconsequence clearly \noutweighdesirable consequences in most settingso Undesirable consequences probably outweigh desirable consequences in most settingso The balance between desirable and undesirable consequences is \nclosely balanced or uncertaino Desirable \nconsequences \nprobably \noutweigh \nundesirable \nconsequences \nin most settingso Desirable \nconsequences clearly outweigh undesirable consequences in most settingso There is insufficient evidence to determine the balance of consequences\nDraft recommendations for \nACIP’s consideration\nDraft recommendations\nChikungunya vaccine is recommended for persons aged ≥18 years \ntraveling to a country or territory where there is a chikungunya \noutbreak\nIn addition, chikungunya vaccine may be considered forthe following \npersons traveling to a country or territory without an outbreak but \nwith evidence of chikungunya virus transmission among humans within \nthe last 5 years\n–Older persons (e.g., >65 years), particularly those with underlying \nmedical conditions, who are likely to have at least moderate exposure to mosquitoes \n–Persons staying for a cumulative period of 6 months or more during a 2-year period\nExample of data supporting recommendation: Substantially higher \nrisk for travelers during outbreak, Paraguay 2023\n<1%\nPercentage of all US persons \ntraveling to areas with \nchikungunya risk visiting Paraguay 26%*\nPercentage of all reported US traveler \nchikungunya cases whose travel \ndestination was Paraguay\n*18 of 69 travelers with destination data, preliminary ArboNET data, 2023\nProviding clarity on chikungunya outbreaks\nFor the purposes of the recommendation, an outbreak \nwill be defined as occurring when CDC posts information on an outbreak on CDC website \nShared clinical decision- making recommendation\nChikungunya vaccine may be considered for the following persons \ntraveling to a country or territory without an outbreak but with \nevidence of chikungunya virus transmission among humans within the last 5 years\n–Older persons (e.g., >65 years), particularly those with underlying \nmedical conditions, who are likely to have at least moderate exposure to mosquitoes \n–Persons staying for a cumulative period of 6 months or more during a 2-year period\nOlder persons, particularly those with underlying medical \nconditions?\nKey risk factors for severe disease \n–Older age \n–Underlying medical conditions\nKey risk factors for chronic arthralgia \n–Older age \n–Presence of pre- existing joint problems\nRisk for higher morbidity and mortality \nin older persons supported by data \nfrom recent outbreak in Paraguay1\n1. Torales M, et al. Notes from the Field: Chikungunya Outbreak - Paraguay, 2022- 2023. MMWR Morb Mortal Wkly Rep 2023; 72:636- 638\nVaccine not \navailable for \nchildren \nCumulative period of ≥6 months during 2 -year period*\nKey risk factor for chikungunya virus infection is intensity of \ntransmission \n–If equivalent transmission, cumulative duration of exposure important\nTransmission patterns can be unpredictable over the longer term and likely to be some seasonal variation in mosquito activity that might \nimpact risk\n*2-year period based on immunogenicity data showing high seroresponse rate (99%) at one year after vaccination \nsuggesting good protection at least through second year but no longer -term data\nEvidence of chikungunya virus transmission among humans \nwithin the last 5 years\nRationale: 5 -year time frame provides interval that allows reasonable \nconfidence there is transmission or insufficient transmission to be concern \nfor travelers \nTool: Map that shows countries \nwith chikungunya virus \ntransmission among humans \nreported during last 5 years, \nposted on CDC website \nMock map to demonstrate transmission of chikungunya virus among \nhumans during last 5 years\nModerate exposure\nModerate exposure could include travelers who might have at least 2 \nweeks (cumulative) of exposure to mosquitoes in indoor and/or \noutdoor settings. It does not include travelers who might have limited exposure to mosquitoes (e.g., those traveling for business and likely to \nbe mainly in mosquito -protected indoor settings)\nGeneral considerations*\n All persons who travel to areas with possible chikungunya virus transmission should be advised to \ntake precautions to avoid mosquito bites\n The risk for chikungunya for most US travelers to countries or territories with evidence of \ntransmission is low. However, some travelers are at increased risk for infection or more severe \ndisease. In the discussion between the healthcare provider and traveler on the need for vaccination, \nconsideration should be given to \n1) whether there is a recognized outbreak or ongoing disease activity \n2) the duration of travel or residence, including likelihood of future travel to an area with \nchikungunya virus transmission\n3) the likelihood of exposure to Aedes mosquitoes\n4) older age (e.g., >65 years)\n5) underlying medical conditions that increase the risk for severe disease (e.g., diabetes, cardiac disease, hypertension)\n6) underlying conditions that increase the risk for chronic arthralgia after infection (e.g., existing joint disease)\n7) an individual’s personal perception and tolerance of risk \n*Provided in background materials\nDraft recommendations\nChikungunya vaccine is recommended for persons aged ≥18 years \ntraveling to a country or territory where there is a chikungunya \noutbreak\nIn addition, chikungunya vaccine may be considered forthe following \npersons traveling to a country or territory without an outbreak but \nwith evidence of chikungunya virus transmission among humans within \nthe last 5 years\n–Older persons (e.g., >65 years), particularly those with underlying \nmedical conditions, who are likely to have at least moderate exposure* to mosquitoes \n–Persons staying for a cumulative period of 6 months or more during a 2-year period\n*Moderate exposure could include travelers who might have at least 2 weeks (cumulative) of exposure to mosquitoes in \nindoor and/or outdoor settings", "summary": "National Center for Emerging and Zoonotic Infectious Diseases EVIDENCE TO RECOMMENDATIONS FOR  CHIKUNGUNYA VACCINE USE AMONG  ADULT TRAVELERS Susan Hills, MBBS, MTH CDC Lead , Chikungunya Vaccines Work Group Arboviral Diseases Branch Division of Vector -Borne Diseases Fort Collins, Colorado ACIP meeting, October 26, 2023 Chikungunya virus and transmission Alphavirus  Primarily transmitted by Aedes  aegypti and Aedes albopictus Uncommon modes of  transmission –Laboratory exposure…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-25-26-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-10-25-26/02-Chikungunya-Hills-508.pdf", "doc_date": "2023-10-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 67}
{"title": "03 Chikungunya Hills 508", "content": "National Center for Emerging and Zoonotic Infectious Diseases\nEVIDENCE TO RECOMMENDATIONS FOR \nCHIKUNGUNYA VACCINE USE AMONG \nLABORATORY WORKERS\nSusan Hills, MBBS, MTH\nCDC Lead , Chikungunya Vaccines Work Group\nArboviral Diseases Branch\nDivision of Vector -Borne Diseases\nFort Collins, Colorado\nACIP meeting, October 26, 2023\nInfections among laboratory workers\nAt least 44 chikungunya virus infections identified among laboratory \nworkers worldwide over ~ 50 years1–3 \n–43 cases overt disease, 1 asymptomatic infection, no deaths\n4 disease cases in US laboratorians since chikungunya became notifiable disease in 2015\n–One case hospitalized for observation, no deaths \nIdentified cases underestimate all infections as no formal laboratory surveillance system\n1.The Subcommittee on Arbovirus Laboratory Safety of the American Committee on Arthropod -Borne Viruses. Am J Trop Med Hyg 1980;\n2.Rusnak JM, et al. J Occup Environ Med 2004; 3. US national arboviral disease surveillance system, 2015 –2022 \nRoutes of transmission\nAerosol \nPercutaneous\n–Needlestick while working with and \ninjecting mice\n–Forceps prick while dissecting mosquitoes infected with chikungunya virus\nMucosal (possible)\n\nPolicy question\nShould chikungunya vaccine be recommended for \nlaboratory staff at risk for chikungunya virus infection? \nLaboratory worker Evidence to Recommendations notes\nSame GRADE assessment as vaccination for travelers\nConsidered data on cross -protection from vaccine against \n3 genotypes of chikungunya virus\n–Only limited data from laboratory studies to confirm cross-\nprotection \n–Chikungunya virus considered single serotype and limited \ngenotype -specific differences in antigenicity \n–No evidence of re -infection in humans with different genotypes\nEvidence to Recommendations: Public health problem\nTopic Decision Comment\nPublic health \nproblemNo, not of public health importance overall•Only occasional US laboratory -acquired \ninfections reported\n•Potential for acute infection with severe polyarthralgia and possible chronic \narthralgia\nValues Laboratorians likely think \ndesirable effects large relative to undesirable effects \nNo important variability•Scientists will understand risks of disease \nand risks and benefits of vaccination\nEvidence to Recommendations: Public health problem\nTopic Decision Comment\nPublic health \nproblemNo, not of public health importance overall•Only occasional US laboratory -acquired \ninfections reported\n•Potential for acute infection with severe polyarthralgia and possible chronic \narthralgia\nValues Laboratorians likely think \ndesirable effects large relative to undesirable effects \nNo important variability•Scientists will understand risks of disease \nand risks and benefits of vaccination\nEvidence to Recommendations: Acceptability\nTopic Decision Comment\nAcceptability Yes, acceptable to key \nstakeholders•Acceptable for occupational health directors, laboratory managers, and laboratorians because will improve safety\nResource use Yes, reasonable and efficient allocation of resources•Limited number of staff undertaking research or specific diagnostic work with chikungunya virus\n•Small cost to avoid impact and costs of worker becoming infected\nEquity Probably increased •If employer offers vaccination, will improve safety for staff and addresses an occupational health issue\nEvidence to Recommendations: Resource use\nTopic Decision Comment\nAcceptability Yes, acceptable to key \nstakeholders•Acceptable for occupational health directors, laboratory managers, and laboratorians because will improve safety\nResource use Yes, reasonable and efficient allocation of resources•Limited number of staff undertaking research or specific diagnostic work with chikungunya virus\n•Small cost to avoid impact and costs of worker becoming infected\nEquity Probably increased •If employer offers vaccination, will improve safety for staff and addresses an occupational health issue\nEvidence to Recommendations: Equity\nTopic Decision Comment\nAcceptability Yes, acceptable to key \nstakeholders•Acceptable for occupational health directors, laboratory managers, and laboratorians because will improve safety\nResource use Yes, reasonable and efficient allocation of resources•Limited number of staff undertaking research or specific diagnostic work with chikungunya virus\n•Small cost to avoid impact and costs of worker becoming infected\nEquity Probably increased •If employer offers vaccination, will improve safety for staff and addresses an occupational health issue\nEvidence to Recommendations: Feasibility\nTopic Decision Comment\nFeasibility Yes, feasible •Likely build on existing occupational \nhealth program\nBalance of consequences\no Undesirable \nconsequences clearly outweighdesirable consequences in most settingso Undesirable consequences probably outweigh desirable consequences in most settingso The balance between desirable and undesirable consequences is \nclosely balanced or uncertaino Desirable \nconsequences \nprobably \noutweigh \nundesirable \nconsequences \nin most settingso Desirable \nconsequences clearly outweigh undesirable consequences in most settingso There is insufficient evidence to determine the balance of consequences\nDraft recommendation \nChikungunya vaccination is recommended for laboratory \nworkers with potential for exposure to chikungunya virus\nInformation accompanying recommendations\nLocal biosafety committee should undertake risk assessment \nof potential for chikungunya virus exposure considering \n–Type of work to be performed \n–Biosafety level at which work is being conducted\nVaccination not necessary for workers handling routine clinical samples \nDraft recommendation \nChikungunya vaccination is recommended for laboratory \nworkers with potential for exposure to chikungunya virus", "summary": "National Center for Emerging and Zoonotic Infectious Diseases EVIDENCE TO RECOMMENDATIONS FOR  CHIKUNGUNYA VACCINE USE AMONG  LABORATORY WORKERS Susan Hills, MBBS, MTH CDC Lead , Chikungunya Vaccines Work Group Arboviral Diseases Branch Division of Vector -Borne Diseases Fort Collins, Colorado ACIP meeting, October 26, 2023 Infections among laboratory workers At least 44 chikungunya virus infections identified among laboratory  workers worldwide over ~ 50 years1–3  –43 cases overt disease, 1…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-25-26-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-10-25-26/03-Chikungunya-Hills-508.pdf", "doc_date": "2023-10-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 15}
{"title": "01 Dengue chen 508", "content": "Centers for Disease Control and Prevention\nNational Center for Emerging and Zoonotic Infectious Diseases\nUpdates on Dengue Vaccines\nWilbur Chen, MD\nOctober 26, 2023\n\nDengue is endemic in\n6U.S. territories and freely associated states.\n\nDengvaxia ™ACIP Recommendation June 2021\nThree doses of Dengvaxia are \nindicated for the prevention of \ndengue disease caused by dengue virus serotypes 1, 2, 3, and 4 in people 9–16 years old with:\n•laboratory confirmation of \nprevious dengue virus infection\nAND\n•living in endemic areas.\n\nTakeda Dengue Vaccine (TAK -003) has been under \nreview by the FDA since Nov 2022\nDengue Workgroup presented to ACIP 3 times\nSep Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov2022 2023\n•Takeda dengue \nvaccine safety and efficacy presentation\n•Workgroup summary and interpretation•Policy questions\n•Cost -effective (CE) analysis \n(CDC/Notre Dame)\n•Comparison of CE models\n•Partial EtR•Dengue epidemiology\n•Review of Sanofi dengue vaccine and ACIP recommendation•Plan to present draft recommendations\nOverall VE\n61.2% (56.0, 65.8%)\nVE in Seropositives\n64.2% (58.4, 69.2%)VE in Seronegatives\n53.5% (41.6– 62.9%)\nVE in Seropositives by Serotype\nDENV -1 56.1% (44.6, 65.2%)\nDENV -2 80.4% (73.1, 85.7%)\nDENV -3 52.3% (36.7, 64.0%)\nDENV -4 70.6% (39.9, 85.6%)VE in Seronegatives by Serotype\nDENV -1 45.4% (26.1, 59.7%)\nDENV -2 88.1% (78.6, 93.3%)\nDENV -3 -15.5% (-108.2, 35.9%)\nDENV -4 -105.6% (-628.7, 42.0%)TAK-003 Efficacy* Outcome: Virologically Confirmed Dengue\nUnpublished data presented by Takeda to ACIP and ASTMH*57 months after first dose, s ignificant results bolded. Number for seropositive placebo \nparticipants 4,855 and vaccine 9,666; Seronegative placebo 1,832 and vaccine 3,714.\nOverall VE\n84.1% (77.8, 88.6%)\nVE in Seropositives\n85.9% (78.7, 90.7%)VE in Seronegatives\n79.3% (63.5, 88.2%)\nVE in Seropositives by Serotype\nDENV -1 66.8% (37.4, 82.3%)\nDENV -2 95.8% (89.6, 98.3%)\nDENV -3 74.0% (38.6, 89.0%)\nDENV -4 100% (NE, NE)†VE in Seronegatives by Serotype\nDENV -1 78.4% (43.9, 91.7%)\nDENV -2 100% (NE, NE)§\nDENV -3 -87.9% (-573.4, 47.6%)¶\nDENV -4 100 % (NE, NE)**TAK-003 Efficacy* Outcome: Hospitalization\n†DENV -4 Placebo events: 3 TAK-003 events: 0§DENV -2 Placebo events: 23    TAK -003 events: 0\n¶DENV -3 Placebo events: 3 TAK-003 events: 11\n**DENV -4 Placebo events: 1 TAK-003 events: 0\n*57 months after first dose, s ignificant results bolded. Number for seropositive placebo \nparticipants 4,855 and vaccine 9,666; Seronegative placebo 1,832 and vaccine 3,714. Unpublished data presented by Takeda to ACIP and ASTMH\nEuropean Medicines Agency (EMA) Committee for \nMedicinal Products for Human Use (CHMP) issued positive opinion for TAK- 003\nOctober 2023\n•EU-M4all: parallel review for EU and participating dengue endemic \ncountries globally \n•TAK-003 vaccine approved in multiple countries\n‒EU, UK, Brazil, Argentina, Indonesia, & Thailand\nOn July 11, Takeda voluntarily withdrew \nTAK-003 from FDA review.\nhttps://www.takeda.com/newsroom/statements/2023/takeda -announces -voluntary -withdrawal -of-US-biologics -license -application -for-dengue -vaccine -candidate -TAK-003/\n\nWHO SAGE Recommendations for TAK -003\nSept 25, 2023\n•Consider for introduction in settings with high dengue disease burden and \nhigh transmission intensity \n•SAGE recommended the vaccine be introduced to children aged 6 to 16 \nyears of age.\n‒Within that age range, the vaccine should be introduced about 1-2 years prior to \nthe age -specific peak incidence of dengue- related hospitalizations. \n‒The vaccine should be administered in a 2 -dose schedule with a 3 -month interval \nbetween doses.\nFuture Dengue Vaccine Work\n•Dengue workgroup will be paused until TAK -003 is re -submitted to FDA or a \nnew vaccine submitted for approval\nACIP Dengue Vaccines Workgroup\nACIP Members\nWilbur Chen (Chair)\nKathy Poehling\nBeth Bell\nVeronica McNally\nCDC Co- Lead\nGabriela Paz -Bailey\nLaura Adams\nEx Officio Members\nKaitlyn Morabito (NIH)\nRalph LeBlanc (FDA)\nIhid Carneiro Leao (FDA)\nKirk Prutzman (FDA)\nSrihari Seshadri (DOD)Liaison RepresentativesElizabeth Barnett (AAP)\nRob Schechter (AIM)\nConsultants\nEdwin Asturias\nRobert Atmar\nAlan Barrett\nIris Cardona\nAnna Durbin\nTony Marfin\nKristen Pierce\nAnita ShetCDC Contributors\nJosh Wong\nMimi Eckert\nRachel Eidex\nAlfonso Hernandez\nSusan HillsTerri Hyde\nMike McNeil\nJorge Munoz\nErin Staples\nCindy Weinbaum\nRita Helfand", "summary": "Centers for Disease Control and Prevention National Center for Emerging and Zoonotic Infectious Diseases Updates on Dengue Vaccines Wilbur Chen, MD October 26, 2023  Dengue is endemic in 6U.S. territories and freely associated states.  Dengvaxia ™ACIP Recommendation June 2021 Three doses of Dengvaxia are  indicated for the prevention of  dengue disease caused by dengue virus serotypes 1, 2, 3, and 4 in people 9–16 years old with: •laboratory confirmation of  previous dengue virus infection AND…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-25-26-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-10-25-26/01-Dengue-chen-508.pdf", "doc_date": "2023-10-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 11}
{"title": "01 COVID Daley 508", "content": "Centers for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nACIP COVID -19 Vaccines Work Group\nDr. Matthew F. Daley, Work Group Chair\nOctober 26, 2023\n▪September 11, 2023\n–FDA authorized the updated mRNA COVID -19 vaccines for use in persons ages 6 \nmonths –11 years under emergency use authorizations (EUAs) \n–FDA approved the updated mRNA COVID -19 vaccines in persons ages ≥ 12 years \nunder supplemental biologics license applications (BLAs) \n▪September 12, 2023\n–ACIP voted to recommend vaccination with updated (2023 –2024 Formula) COVID -19 \nvaccines as authorized under EUA or approved by BLA in persons aged ≥6 months\n▪October 3, 2023\n–FDA authorized the updated (2023 –2024 Formula) Novavax COVID -19 vaccine for use \nin persons aged ≥12 years under EUACOVID -19 vaccine updates\nNote: Updated (2023 –2024 Formula) COVID -19 vaccines are monovalent vaccines containing an XBB.1.5 component\nReviewed and discussed:\n▪COVID -19 vaccine safety\n▪COVID -19 vaccine implementationACIP COVID -19 Work Group Meeting Review\nOctober 2023\n▪COVID -19 vaccine implementation Dr. Shannon Stokley\n▪COVID -19 policy updates Dr. Megan Wallace\n▪DiscussionAgenda\nOctober 26, 2023\nWork Group members\nACIP members\n▪Matthew Daley (chair)\n▪Beth Bell \n▪Grace Lee\n▪Keipp Talbot\n▪Oliver Brooks\nEx-officio/government members\n▪FDA: Rachel Zhang, Lucia Lee, Anuja Rastogi\n▪NIH: Chris Roberts, Michael Ison\n▪IHS: Uzo Chukwuma\n▪CMS: Jeff Kelman\n▪BARDA: Christine Oshansky\n▪HHS: Valerie Marshall\n▪CDC: Alan Lam\nCDC Lead\n▪Megan Wallace\n5Liaisons\n▪AAFP: Jonathan Temte\n▪AAP: Sean O’Leary\n▪ACOG: Denise Jamieson (primary), \nLaura Riley (alternate)\n▪ACP: Jason Goldman\n▪ADS: Emily Kahn\n▪AGS: Ken Schmader\n▪AMA: Sandra Fryhofer\n▪ANA: Ruth Francis (alternate)\n▪APA: Richard Dang\n▪ASTHO: Marcus Plescia\n▪CSTE: Paul Cieslak, Christine Hahn\n▪IDSA: Jeff Duchin (primary)Liaisons, cont’d\n▪NACCHO: Matt Zahn (primary), \nJeff Duchin (alternate)\n▪NACI: Matthew Tunis (primary),    \nEva Wong (alternate)  \n▪NFID: Rob Schechter (primary),        \nBill Schaffner (alternate)\n▪NMA: Patricia Whitley -Williams\n▪SHEA: Preeti Mehrotra,                \nMarci Drees (alternate)\nConsultants\n▪Ed Belongia\n▪Hank Bernstein\n▪Kathy Edwards\n▪Robert Hopkins\n▪Lisa Jackson\n▪Kathy Kinlaw\n▪Dayna Matthew ▪Jennifer Nelson\n▪Kathleen Neuzil\n▪Stanley Perlman\n▪Peter Szilagyi\n▪Sarah Meyer\n▪Elisha Hall\n▪Danielle Moulia\n▪Monica Godfrey\n▪Hannah Rosenblum\n▪Katherine Fleming -Dutra\n▪Ruth Link -Gelles\n▪Lauren Roper \n▪Mary Chamberland\n▪Susan Goldstein\n▪Stephen Hadler\n▪JoEllen Wolicki\n▪Melinda Wharton\n▪Jessica MacNeil\n▪Amanda Cohn\n▪Brooke Aspinwall \n▪Latifa Boyce CDC participants\n6▪Amadea Britton\n▪Karen Broder \n▪Carolyn Bridges\n▪Allison Ciesla \n▪Nicole Dowling\n▪Daniel Drapeau\n▪Tarayn Fairlie\n▪Ashley Fowlkes\n▪Julianne Gee\n▪Samuel Graitcer\n▪Lisa Grohskopf\n▪Katherine Grusich\n▪Aron Hall \n▪Demorah Hayes\n▪Rita Helfand\n▪Terri Hyde\n▪Jefferson Jones ▪Melisa Shah\n▪Tom Shimabukuro\n▪Jordan Singleton\n▪Laura Steinhardt\n▪John Su\n▪Natalie Thornburg\n▪Evelyn Twentyman \n▪Dennis Wang\n▪Raigan Wheeler\n▪Ryan Wiegand\n▪Patricia Yu\n▪Yon Yu▪Andrew Kroger\n▪Josephine Mak\n▪Lauri Markowitz\n▪Michael McNeil\n▪Michael Melgar\n▪Noelle -Angelique Molinari\n▪Morgan Najdowski\n▪Kristen Nordlund\n▪Sara Oliver \n▪Ismael Ortega -Sanchez\n▪Manisha Patel\n▪Pragna Patel\n▪Amanda Payne\n▪Georgina Peacock\n▪Jamison Pike \n▪Derrell Powers\n▪Sierra Scarbrough\nFor more information, contact CDC\n1-800 -CDC -INFO (232 -4636)\nTTY:  1 -888 -232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention.\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nThank you", "summary": "Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. ACIP COVID -19 Vaccines Work Group Dr. Matthew F. Daley, Work Group Chair October 26, 2023 ▪September 11, 2023 –FDA authorized the updated mRNA COVID -19 vaccines for use…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-25-26-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-10-25-26/01-COVID-Daley-508.pdf", "doc_date": "2023-10-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 7}
{"title": "02 COVID Stokley 508", "content": "Centers for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nImplementation Update on \n2023 –2024 COVID -19 Vaccines\nShannon Stokley, DrPH\nImmunization Services Division\nCenters for Disease Control and Prevention\nCommercialization Transition\n▪The CDC COVID -19 Vaccination Program discontinued on:\n–September 12, 2023, as applied to the bivalent Moderna and Pfizer -BioNTech \nCOVID -19 vaccines\n–October 3, 2023, as applied to the ancestral (Original) Novavax COVID -19 Vaccine\n▪Providers are encouraged to:\n–Continue administering COVID -19 vaccine through their offices/pharmacies/other \npractices\n–Participate in vaccines.gov\n▪Vaccine data reporting has transitioned to routine reporting processes for \njurisdictions that have signed data use agreement (DUA) with CDC.U.S. Government Vaccination Program Discontinuation\n▪Updated COVID -19 vaccines are available to most people living in the U.S. \nat no cost through their private health insurance, Medicare, and Medicaid \nplans.Vaccine Cost/Insurance\n*Adults with health insurance that does not cover all COVID -19 vaccine costs, at any Bridge Access Program site which is in-network for their health insurance.Private health \ninsurance\nPlans that are ACA -\ncompliant c over COVID -\n19 vaccines from an in -\nnetwork provider at no \ncost -sharing.Medicare and Medicaid\nCover COVID -19 \nvaccines at no -cost \nsharingGovernment programs\nProvide vaccine at no cost for:\n•VFC: Children through 18 years that \nare Medicaid eligible, uninsured, \nAmerican Indian/Alaska Native, or \nunderinsured\n•Bridge Access Program: Adults ages \n18 years and older who are \nunderinsured* or uninsured\n▪There is increasing supply of vaccine to meet demand.\n–Moderna, Pfizer -BioNTech, and Novavax are available.\n▪CDC is continuing to have conversations with manufacturer and \ndistributors to ensure timely distribution of COVID -19 vaccines.\n▪Visit vaccines.gov to find a COVID -19 vaccine near you.Vaccine Availability\nBridge Access Program\n▪CDC’s Bridge Access Program provides no -cost COVID -19 vaccines to \nadults without health insurance and adults whose insurance does not \ncover all COVID -19 vaccination costs.\n–All CDC -recommended COVID -19 vaccines are included in the Bridge Access \nProgram.\n–The Bridge Access Program will end by December 31, 2024.\n–The Vaccines for Adults (VFA) program, proposed in the FY 2023 and 2024 \nPresidential Budget, would be a long -term solution to ensure all adults have access \nto recommend vaccinations, including COVID -19 vaccines, at no cost to them.CDC’s Bridge Access Program\nAdults 18 years and older without health insurance\n-and -\nAdults with health insurance that does not cover all COVID -19 \nvaccine costs (only at Bridge Access Program sites that are in-\nnetwork for their health insurance)Who Can Get a No -Cost COVID -19 Vaccine Through the \nBridge Program\nWhere to Get a No -Cost COVID -19 Vaccine through the \nBridge Access Program? \nVisit Vaccines.gov to find a provider that offers no -cost COVID -19 \nvaccines through the Bridge Access Program!\nCommunity \nevents or \npop-up sites \nwith these \ngroups\nLocal Healthcare Providers\nRetail Pharmacies:\nWalgreens, CVS, eTrueNorth (pharmacy aggregator)HRSA -Supported Centers\nBridge Program Ordering and Administration*\n*Data as of 10/20/2023\nThere are >24,000 contracted pharmacy locations and\n>380,000 doses have been administered by contracted \npharmacies to individuals without insurance in the U.S.Rx\n>4,400 public health safety net providers have placed >6,100 \norders for > 287,000 doses of COVID -19 vaccine using 317 funds. \nNationally, 81% of people without insurance are estimated to be \nwithin a 5-mile drive distance to a Bridge Access Program provider.\nVaccination Coverage\nSnapshot of COVID -19 vaccine data reporting plans\nAdministration data from reporting states National Immunization Surveys\nBridge Access Program for COVID -19 Vaccines\nOther surveillance systems\nVaccine Safety Datalink\nOther data sources\nOmnibus surveys\nInternet panel survey of pregnant people\nDistribution data\nNational Healthcare \nSafety Network\nAmong 14,715 adults ages 18 years and older, 7.1% reported having \nreceived a COVID -19 vaccine since September 14, 2023.\nCOVID -19 Vaccination Status and Intent Among Adults Age ≥18 Years by Demographics, \nNational Immunization Survey -Adult COVID Module, October 8 –14, 2023\nProbably or definitely will NOT get vaccinatedUp to date with 2023 -24 COVID -19 vaccine\nDefinitely will get vaccinated\nProbably will get vaccinated or unsure0.88.110.23.57.68.34.64.97.08.22.32.64.77.515.420.56.57.77.1\n31.215.123.219.323.927.224.422.924.525.516.520.323.928.730.836.222.327.024.6\n21.535.227.946.139.623.151.926.530.732.035.733.035.426.026.025.930.930.430.6\n46.541.638.731.228.941.419.145.737.834.345.544.135.937.827.717.440.334.937.6\n0 25 50 75 100AI/ANMulti/OtherNH/OPI**HispanicBlackWhiteAsianRuralSuburbanUrban18-2930-3940-4950-6465-7475+MaleFemaleOverall\nWeighted %12.57.04.77.27.14.05.89.01.77.8\n31.124.635.224.518.818.424.930.215.226.2\n35.230.431.229.434.244.531.323.944.028.9\n21.238.028.938.839.933.138.136.839.137.1\n0 25 50 75 100Transgender/NonbinaryCisgenderGay/Lesbian/Bisexual/OtherStraightIncome unknownBelow povertyAbove poverty, <$75kAbove poverty, ≥$75kNot insuredInsured\nWeighted %\nReceipt of a COVID -19 vaccine was more frequently reported among \nadults who were older, insured, and with higher incomes.\nCOVID -19 Vaccination Status and Intent Among Adults Age ≥18 Years by Demographics, \nNational Immunization Survey -Adult COVID Module, October 8 –14, 2023\nProbably or definitely will NOT get vaccinatedUp to date with 2023 -24 COVID -19 vaccine\nDefinitely will get vaccinated\nProbably will get vaccinated or unsure0.88.110.23.57.68.34.64.97.08.22.32.64.77.515.420.56.57.77.1\n31.215.123.219.323.927.224.422.924.525.516.520.323.928.730.836.222.327.024.6\n21.535.227.946.139.623.151.926.530.732.035.733.035.426.026.025.930.930.430.6\n46.541.638.731.228.941.419.145.737.834.345.544.135.937.827.717.440.334.937.6\n0 25 50 75 100AI/ANMulti/OtherNH/OPI**HispanicBlackWhiteAsianRuralSuburbanUrban18-2930-3940-4950-6465-7475+MaleFemaleOverall\nWeighted %12.57.04.77.27.14.05.89.01.77.8\n31.124.635.224.518.818.424.930.215.226.2\n35.230.431.229.434.244.531.323.944.028.9\n21.238.028.938.839.933.138.136.839.137.1\n0 25 50 75 100Transgender/NonbinaryCisgenderGay/Lesbian/Bisexual/OtherStraightIncome unknownBelow povertyAbove poverty, <$75kAbove poverty, ≥$75kNot insuredInsured\nWeighted %\n2.12.72.70.72.22.41.42.1\n0 2 4 6 8 10Other/multiple races, non-HispanicBlack, non-HispanicWhite, non-HispanicHispanic12-17 years5-11 years6 months-4 yearsAll children\nPercent2.1% of children were reported to have received the updated 2023 -24 \nCOVID -19 vaccination since it was recommended on September 14th, \n2023.2023 -24 COVID -19 Vaccination Coverage, \nChildren Ages 6 Months -17 Years, National Immunization Survey -Child Covid Module (NIS -CCM)\nInterviews week of: 10/8/2023 -10/14/2023 (n=2,767)​\n3.10.81.52.71.40.92.80.83.1\n0 2 4 6 8 10UninsuredOther insuranceAny MedicaidRuralSuburbanUrbanUnknown incomeBelow povertyAbove poverty, <$75,000/yearAbove poverty, >=$75,000/year\nPercent\nParents’ intent to get their child vaccinated was mixed.\nPercentages vaccinated are all <3% and do not show well on this slide, please see previous slide.\n2023 -24 COVID -19 Vaccination Coverage and Parental Intent, \nChildren Ages 6 Months -17 Years, National Immunization Survey -Child Covid Module (NIS -CCM)\nInterviews week of: 10/8/2023 -10/14/2023 (n=2,767)​\n25.430.525.326.529.225.823.226.4\n41.939.927.440.136.630.934.733.8\n30.626.944.632.732.040.940.737.7\n0 20 40 60 80 100Other/multiple races, non-HispanicBlack, non-HispanicWhite, non-HispanicHispanic12-17 years5-11 years6 months-4 yearsAll children\nPercent23.728.025.219.524.831.720.023.522.432.5\n33.032.933.020.234.937.641.930.433.431.2\n43.336.040.958.837.629.437.343.443.433.2\n0 20 40 60 80 100UninsuredOther insuranceAny MedicaidRuralSuburbanUrbanUnknown incomeBelow povertyAbove poverty, <$75,000/yearAbove poverty, >=$75,000/year\nPercent\n▪NIS data collected October 8 -14, 2023 provides estimates about four weeks since the \nSeptember 14, 2023 rollout of the 2023 -24 COVID -19 vaccine\n▪Children (6 months –17 years)\n–2.1% (95% CI: 1.1 -3.0) of children had received the updated 2023 -24 COVID -19 vaccine \n–Slightly more than a quarter of children (33.8%, 95% CI: 30.6 -37.1) have a parent who said they \ndefinitely will get their child vaccinated while 2 in 5 children (37.7%, 95% CI: 34.4 -41.0) have a parent \nthat said they probably or definitely will not get their child vaccinated\n▪Adults (≥18 years)\n–7.1% (95% CI: 6.3 -8.0) of adults had received the updated 2023 -24 COVID -19 vaccine\n–24.6% (95% CI: 23.0 -26.2) of adults said they definitely will get vaccinated, and 37.6% (95% CI: 35.7 -\n39.5) said they probably or definitely will not get vaccinatedCOVID Vaccination Coverage Summary\nFor more information, contact CDC\n1-800 -CDC -INFO (232 -4636)\nTTY:  1 -888 -232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention.\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.", "summary": "Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. Implementation Update on  2023 –2024 COVID -19 Vaccines Shannon Stokley, DrPH Immunization Services Division Centers for Disease Control and Prevention Commercialization…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-25-26-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-10-25-26/02-COVID-Stokley-508.pdf", "doc_date": "2023-10-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 18}
{"title": "04 COVID Wallace 508", "content": "cdc.gov/coronavirus\nSummary and Work Group \nConsiderations\nMegan Wallace, DrPH, MPH\nACIP Meeting\nJune 23 , 2023\nU.S. COVID -19 vaccine uptake among ages ≥12 years, \nAugust 2021 -June 2023\n01,000,0002,000,0003,000,0004,000,0005,000,0006,000,0007,000,000\nPrimary Series, Adolescents Ages 12-17 Primary Series, Adults Ages 18-49 Primary Series, Adults Ages 50-64 Primary Series, Adults Ages 65+\nBooster, Adolescents Ages 12-17 Booster, Adults Ages 18-49 Booster, Adults Ages 50-64 Booster, Adults Ages 65+Primary series authorization \n1stbooster authorization \n2ndbooster authorization 1stbivalent booster \nauthorization \n2ndbivalent \nbooster \nauthorization Doses Administered\nSource: IZ Data Lake \nCoverage / Age (years) <22–45–1112–1718–2424–4950–64>65\nAt least one dos e† 8.9 10.9 40.0 72.2 82.3 85.5 95.0 95.0\nAt least one bivalent dose 0.6 0.6 4.8 7.8 7.4 12.1 21.7 43.3\nUnvaccinated 91.1 89.1 60.0 27.8 17.7 14.5 —†—†U.S. COVID -19 Vaccination Coverage (%) of Total Population by \nAge Group —May 10, 2023\n†Note: Coverage is capped at 95%\nSource: https://covid.cdc.gov/covid -data -tracker/#vaccination -demographics -trends Updated June 1, 2023 3\nPI=Prediction Interval, VOC=Variants of Concern, VBM=Variants Being Monitored . https://covid.cdc.gov/covid -data-tracker/#variant -proportions Accessed June 1 , 2023Trends in weighted variant proportion estimates & Nowcast\nUnited States, February 19, 2023 –June 10, 2023\nCollection date, week ending\n4\n\nWeekly population -based rates of COVID- 19-associated hospitalizations \nby age group— COVID-NET, March 2020–May 2023\nAge Group\n. \nhttps://covid.cdc.gov/covid -data -tracker/#covidnet -hospitalization -network Accessed June, 2023\n5\n▪COVID -19 during pregnancy is associated with severe maternal health outcomes and \nadverse pregnancy outcomes\n▪Risk of complications lower, but still elevated, during the Omicron predominant \nperiod compared to pre -Omicron period\n–Possibly due to the impact of prior infection and vaccination\n▪Most hospitalized pregnant persons with a positive SARS -CoV-2 test were not up to \ndate with vaccinationsCOVID -19 in pregnant people\nSummary\n6\n▪COVID -19-associated hospitalization rates in infants ages 0 –5 months increased in \nthe Omicron period\n–Hospitalization rates similar to those in adults ages 65 –75 years\n▪Majority of infants ages 0 –5 months hospitalized with a positive SARS -CoV-2 test \nwere hospitalized with COVID -19-like symptoms\n▪Vaccination at any point in pregnancy appears to be beneficial to infants <6 monthsCOVID -19 in infants\nSummary\n7\n▪Pregnancy remains a risk factor for severe maternal disease and adverse pregnancy \noutcomes, even with new variants\n▪COVID -19 vaccination improves outcomes for pregnant people, their pregnancies and \ntheir infants\n▪Growing body of evidence that COVID -19 mRNA vaccines are safe during pregnancy1\n▪Current uptake of updated COVID -19 vaccine is low among pregnant people\n–23% of pregnant people received an updated dose2\n▪Work group emphasized that pregnant people should receive recommended COVID -19 \nvaccine dose for protection of themselves and their infants\n▪Continue to review data and evaluate COVID -19 recommendations for pregnant \npeople as neededWork Group interpretation\nCOVID -19 in pregnant people and infants\n1. https://www.cdc.gov/vaccinesafety/research/publications/index.html . COVID -19 Vaccine Safety Articles and Studies by Topic. Pregnancy. \n2. https://covid.cdc.gov/covid -data -tracker/#vaccinations -pregnant -women 8\n▪Hybrid immunity likely provides better protection than either infection or \nvaccination alone\n▪Protection likely influenced by cumulative number of vaccine doses, number of \ntimes infected, timing of most recent vaccination or infection, and how closely the \ncirculating variant matches the vaccine or prior infection\n▪Protection can wane over time after both infection and vaccination\n▪Receipt of updated vaccine dose can provide additional protection beyond that \nreceived by prior doses or infection and restore protection after waningInfection -induced and hybrid immunity\nSummary\n9\nCurrent recommendations for mRNA COVID -19 vaccines\n≥6 years 6 months –4 years 5 years2 doses \nbivalent \nModerna3 doses \nbivalent \nPfizer-\nBioNTechOR2 doses \nbivalent \nModerna1 dose \nbivalent \nPfizer-\nBioNTechOR1 dose \nbivalent \nModerna1 dose \nbivalent \nPfizer -\nBioNTechOR\nCurrent recommendations for mRNA COVID -19 vaccines\n6 –23months 2 –4 yearsQuestion discussed by the Work Group : \nDo children ages 2 –4 years continue to \nneed a multi -dose initial series, or could \nthey also move to a single (annual?) dose \nlike older populations \n\nPossible future recommendations for simplification \nmRNA COVID -19 vaccines\n≥2 years 6–23months2 doses \nbivalent \nModerna3 doses \nbivalent \nPfizer -\nBioNTechOR1 dose \nbivalent \nModerna1 dose \nbivalent \nPfizer-\nBioNTechOR\nCOVID -19-associated hospitalization rates in infants, children and adolescents aged 6 \nmonths through <18 Years —COVID -NET, March 2020 –May 2023\nSource: COVID -NET: https://www.cdc.gov/coronavirus/2019 -ncov/covid -data/covid -net/purpose -methods.html . Data March 1, 2020 through March 31, 2023. Pre -Delta: March 1, 2020 –June \n19, 2021; Delta: June 20 –December 18, 2021; Omicron BA.1: December 19, 2021 –March 19, 2022; Omicron BA.2: March 20 –June 18, 2022; Omicron BA.5 (J une 19, 2022 –May 27, 2023)Pre-Delta DeltaOmicron\nBA.1Omicron\nBA.2Omicron BA.5 and later\n1302468101214161820\n3/7/2020\n4/7/2020\n5/7/2020\n6/7/2020\n7/7/2020\n8/7/2020\n9/7/2020\n10/7/2020\n11/7/2020\n12/7/2020\n1/7/2021\n2/7/2021\n3/7/2021\n4/7/2021\n5/7/2021\n6/7/2021\n7/7/2021\n8/7/2021\n9/7/2021\n10/7/2021\n11/7/2021\n12/7/2021\n1/7/2022\n2/7/2022\n3/7/2022\n4/7/2022\n5/7/2022\n6/7/2022\n7/7/2022\n8/7/2022\n9/7/2022\n10/7/2022\n11/7/2022\n12/7/2022\n1/7/2023\n2/7/2023\n3/7/2023\n4/7/2023\n5/7/2023Rate per 100,000\n6 months <2 years 2-4 years 5-11 years 12-17 years\n63828993\n0102030405060708090100\nMar-Apr May-Jun Jul-Aug Sep-Oct Nov-DecSeroprevalence (%)\nMonth7585929799\n0102030405060708090100\nMar-Apr May-Jun Jul-Aug Sep-Oct Nov-DecSeroprevalence (%)\nMonthPediatric infection -induced and combined (vaccine -and infection -induced) \nSeroprevalence from U.S. commercial laboratories —March –December 2022\nSource: https://covid.cdc.gov/covid -data -tracker/#pediatric -seroprevalence and unpublished data (CDC) Data from repeat, cross -sectional study on blood specimens collected by commercial laboratories. \nVaccine history is unknown in this study. Infection -induced seroprevalence estimated from blood specimens tested for anti -nucleo capsid antibodies: the number of specimens per 2 -month collection \nperiod were, by age group: 6 –11 months: 157; 12 –23 months: 724; 2 –4 years: 2,165; 5 –11 years: 9,247; and 12 –17 years: 14,570.  C ombined (vaccine -and infection -induced seroprevalence estimated \nfrom specimens tested for both spike and nucleocapsid antibodies: >99% of samples tested for anti -nucleocapsid antibodies were t ested for anti -spike antibodies. 14Infection -induced Combined (vaccine -and infection -induced) \n\n▪Children ages 6 –23 months have higher COVID -19 hospitalization rates; hospitalization \nrates among children ages 2 –4 years similar to rates in children 5 –17 years\n▪Children ages ≥2 years more likely to be seropositive and may have multiple exposures \nthrough either infection or vaccination\n▪However, no randomized, clinical trials compared efficacy or immunogenicity of single \ndose versus multiple dose in young pediatric population in the context of high \nseroprevalence Children ages 2 –4 years\nMultiple initial doses or single (annual?) dose\n15\n▪COVID -19 vaccines effectively protect children from hospitalization and severe disease \nfrom COVID -19\n–Uptake of COVID -19 vaccines in children remains low\n▪Work Group would be supportive of a move toward recommendation for a single \n(possibly annual) dose in ages 2 –4 years based on hospitalization rates and rates of \nseropositivity in this age group\n–Work Group did highlight differences in transition to a single dose series from a two-dose \nseries , compared to a three -dose series\n▪Simple recommendations may lead to increased coverage\n▪Continue to review data and evaluate COVID -19 vaccine program in context of evolving \nepidemiology Work Group interpretation \nMultiple doses in children ages 2 -4 years\n16\n▪June 15, 2023 FDA’s Vaccines and Related Biological Products Advisory Committee \n(VRBPAC) met to discuss fall strain composition\n▪VRBPAC unanimously voted that the vaccine composition be updated to a \nmonovalent COVID -19 vaccine with an XBB -lineage of the Omicron variant\n▪FDA advised manufacturers to develop vaccines with a monovalent XBB.1.5 \ncomposition\n▪Anticipate updated vaccine doses will be broadly available in the fall \n▪Following updated vaccine authorizations, ACIP will review evidence to inform \nupdated recommendationsSteps toward recommendation of updated vaccine\nhttps://www.fda.gov/advisory -committees/advisory -committee -calendar/vaccines -and-related -biological -products -advisory -committee -june -15-2023 -meeting -announcement\nhttps://www.fda.gov/vaccines -blood -biologics/updated -covid -19-vaccines -use-united -states -beginning -fall-2023 17\n▪COVID -19 vaccines and treatments will likely transition to the commercial \nmarketplace in fall 2023\n–CDC continues to partner closely with state, local, and interagency partners toward \ncontinued successful distribution of COVID -19 vaccines and treatments during this time, \nincluding clarification of processes for ordering, shipping and distribution\n–Guidance for partners will be published in summer 2023, prior to the transition to the \ncommercial marketplace\n▪Most Americans will continue to pay nothing out -of-pocket for the COVID -19vaccine \ndue to their insurance coverage\n▪However, approximately 25 million uninsured adults will lose access to affordable \nCOVID -19 vaccines and treatments if no action were taken\n▪The Bridge Access Program for COVID -19 Vaccines and Treatment is a public -private \npartnership which serves as a temporary measure to prevent the loss of under -and \nuninsured adults' access to COVID -19 vaccines and treatments at no -cost after \ncommercializationPlanning for Fall 2023\n18\n▪COVID -19 continues to cause substantial morbidity and mortality across the population, \nparticularly in groups like older adults and persons with immunocompromising conditions\n▪COVID -19 vaccines continue to be the most effective tool we have to prevent serious illness, \nhospitalization and death from COVID -19 \n▪COVID -19 vaccination is important for pregnant people for the protection of themselves and \ntheir infants\n▪Most of the population hasn’t received a bivalent vaccine dose\n▪Ongoing review of data to continue efforts toward simplification\n–Work Group would be supportive of additional simplification for children ages 2 –4 years in the future \n▪FDA advised manufacturers to develop vaccines with a monovalent XBB.1.5 composition\n▪Anticipate benefits from updated vaccine prior to possible increases in cases over the winter; \nACIP can discuss future vaccine recommendations at upcoming meetings following updated \nvaccine authorizationsSummary\n19\n▪Sara Oliver\n▪Danielle Moulia\n▪Monica Godfrey\n▪Evelyn Twentyman\n▪Hannah Rosenblum\n▪Lauren Roper\n▪Katherine Fleming -Dutra\n▪Ruth Link -Gelles\n▪Amadea Britton\n▪Sarah Meyer\n▪Susan Goldstein\n▪Mary Chamberland\n▪Elisha Hall\n▪Valerie Morelli▪JoEllen Wolicki\n▪Fiona Havers\n▪Romeo Galang\n▪Sierra Scarbrough\n▪Jefferson Jones\n▪Aron Hall\n▪Barbara Mahon\n▪Coronavirus and other Respiratory Viruses Division\n▪National Center for Immunization and Respiratory \nDiseasesAcknowledgments\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the \nofficial position of the Centers for Disease Control and Prevention.\nThank you", "summary": "cdc.gov/coronavirus Summary and Work Group  Considerations Megan Wallace, DrPH, MPH ACIP Meeting June 23 , 2023 U.S. COVID -19 vaccine uptake among ages ≥12 years,  August 2021 -June 2023 01,000,0002,000,0003,000,0004,000,0005,000,0006,000,0007,000,000 Primary Series, Adolescents Ages 12-17 Primary Series, Adults Ages 18-49 Primary Series, Adults Ages 50-64 Primary Series, Adults Ages 65+ Booster, Adolescents Ages 12-17 Booster, Adults Ages 18-49 Booster, Adults Ages 50-64 Booster, Adults Ages…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/04-COVID-Wallace-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 21}
{"title": "01 COVID Daley 508", "content": "cdc.gov/coronavirus\nACIP COVID -19 Vaccines Work Group\nDr. Matthew F. Daley, Work Group Chair\nApril 19, 2023\n▪April 18, 2023: FDA1updated COVID -19 vaccine emergency use authorizations \n(EUAs):\n–Use of bivalent mRNA vaccines for all doses/indications administered to individuals \nages 6 months and older\n–Additional dose(s) for certain populationsCOVID -19 vaccine update:\nFDA authorizations\n21. https://www.fda.gov/news -events/press -announcements/coronavirus -covid -19-update -fda-authorizes -changes -simplify -use-bivalent -mrna-covid -19-vaccines\n▪Review of pediatric COVID -19 vaccine data\n▪Epidemiology of COVID -19, including among adults ≥65 years of age\n▪Vaccine effectiveness (VE) updates\n▪Preliminary results for pediatric cost effectiveness analyses\n▪Discussions for additional doses in vulnerable populationsACIP COVID -19 Work Group Meeting Review\nMarch –April 2023\n3\n▪Vaccine safety updates\n▪Vaccine effectiveness data updates \n▪Epidemiology and hospitalization data \n▪Benefit -risk analysis\n▪Considerations for transition to bivalent primary series \n▪Future directions of COVID -19 vaccines, including updates to vaccine policyFebruary ACIP COVID -19 Meeting Review\nFebruary 24, 2023\n4\n▪COVID -19 vaccine program updates Dr. Peacock (CDC)\n▪COVID -19 vaccine safety updates Dr. Shimabukuro (CDC)\n▪Update: v -safe after vaccination health checker Dr. Shimabukuro (CDC)\n▪Updates to COVID -19 vaccine effectiveness in the US Dr. Link -Gelles (CDC)\n▪Updates to COVID -19 vaccine policy: \nData and Work Group considerations Dr. Oliver (CDC)\n▪Updates to Interim Clinical Considerations Dr. Twentyman (CDC)\nBreak\n▪Public Comment\n▪DiscussionAgenda: \nWednesday April 19, 2023\nACIP members\n▪Matthew Daley (chair)\n▪Beth Bell \n▪Grace Lee\n▪Keipp Talbot\n▪Oliver Brooks\nEx-officio/government members\n▪FDA: Rachel Zhang, Lucia Lee, Anuja Rastogi\n▪NIH: Chris Roberts\n▪IHS: Uzo Chukwuma\n▪CMS: Jeff Kelman\n▪BARDA: Christine Oshansky\n▪HHS: David Kim\n▪CDC: Alan Lam\nCDC Leads\n▪Sara Oliver\n▪Evelyn TwentymanWork Group members\n6Liaisons\n▪AAFP: Jonathan Temte\n▪AAP: Sean O’Leary\n▪ACOG: Denise Jamieson (primary), \nLaura Riley (alternate)\n▪ACP: Jason Goldman\n▪ADS: Emily Kahn\n▪AGS: Ken Schmader\n▪AIM: Rob Shechter (primary), \nJane Zucker (alternate)\n▪AMA: Sandra Fryhofer\n▪ANA: Ruth Francis (alternate)\n▪APhA: Michael Hogue\n▪ASTHO: Marcus Plescia\n▪CSTE: Paul Cieslak, Christine Hahn\nIDSA: Jeff Duchin (primary)Liaisons, cont’d\n▪NACCHO: Matt Zahn (primary), \nJeff Duchin (alternate)\n▪NACI: Matthew Tunis (primary),\nNicole Forbes (alternate)\n▪NFID: Bill Schaffner (primary), \nMarla Dalton (alternate)\n▪NMA: Patricia Whitley -Williams\n▪SHEA: Preeti Mehrotra\nMarci Drees (alternate) \nConsultants\n▪Ed Belongia \n▪Kathy Kinlaw \n▪Dayna Matthew \n▪Kathleen Neuzil \n▪Stanley Perlman \n▪Peter Szilagyi\n▪Hank Bernstein\n▪Sarah Meyer\n▪Elisha Hall\n▪Megan Wallace\n▪Danielle Moulia\n▪Lauren Roper\n▪Hannah Rosenblum\n▪Katherine Fleming -Dutra\n▪Monica Godfrey\n▪Susan Goldstein\n▪Mary Chamberland\n▪Stephen Hadler\n▪JoEllen Wolicki\n▪Melinda Wharton\n▪Jessica MacNeil\n▪Amanda CohnCDC participants\n7▪Ruth Link -Gelles\n▪Amadea Britton\n▪Carolyn Bridges\n▪Allison Ciesla \n▪Nicole Dowling\n▪Ashley Fowlkes\n▪Heather Scobie\n▪Natalie Thornburg\n▪Tom Shimabukuro\n▪John Su\n▪Julianne Gee\n▪Karen Broder\n▪Rita Helfand\n▪Jefferson Jones\n▪Yvonne Bolen▪Pragna Patel \n▪Amanda Payne\n▪Georgina Peacock\n▪Jose Romero\n▪Laura Steinhardt\n▪Ryan Wiegand\n▪Patricia Yu\n▪Yon Yu▪Samuel Graitcer\n▪Lisa Grohskopf\n▪Katherina Grusich\n▪Aaron Hall\n▪Terri Hyde\n▪Cynthia Jorgensen\n▪Kristen Nordlund\n▪Sierra Scarbrough\n▪Edwin Shanley\n▪Andrew Kroger\n▪Lauri Markowitz\n▪Noelle -Angelique Molinari\n▪Michael McNeil\n▪Morgan Najdowski\n▪Ismael Ortega -Sanchez\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the \nofficial position of the Centers for Disease Control and Prevention.\nThank you!", "summary": "cdc.gov/coronavirus ACIP COVID -19 Vaccines Work Group Dr. Matthew F. Daley, Work Group Chair April 19, 2023 ▪April 18, 2023: FDA1updated COVID -19 vaccine emergency use authorizations  (EUAs): –Use of bivalent mRNA vaccines for all doses/indications administered to individuals  ages 6 months and older –Additional dose(s) for certain populationsCOVID -19 vaccine update: FDA authorizations 21. https://www.fda.gov/news -events/press -announcements/coronavirus -covid -19-update -fda-authorizes…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-19-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-04-19/01-COVID-Daley-508.pdf", "doc_date": "2023-04-19", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 8}
{"title": "02 COVID Peacock 508", "content": "For more information: www.cdc.gov/COVID19\nCOVID -19 Vaccine Program Updates\nGeorgina Peacock, MD, MPH, FAAP\nDirector, Immunization Services Division\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention (CDC)\nOverarching Objectives for the U.S. COVID -19 \nVaccination Program\nEnsure safety and \neffectiveness of \nCOVID -19 \nvaccinesReduce mortality, \nmorbidity, and \nincidence of \nCOVID -19 diseaseHelp minimize \ndisruption to \nsociety and \neconomy, including \nmaintaining \nhealthcare capacityEnsure equity in \nvaccine allocation \nand distribution\nEnd of the Public Health Emergency on May 11, 2023\nand the COVID -19 Vaccination Program\n▪What will change\n▪Possible reduced submission of vaccine administration data from some \njurisdictions which may limit completeness of administration data on a national \nlevel\n▪Most jurisdictions have signed a COVID -19 vaccine Data Use Agreement extension \nthrough the end of 2023\nEnd of the Public Health Emergency on May 11, 2023\nand the COVID -19 Vaccination Program\n•What will notchange\n▪CDC working with public and private partners to learn more about the short -and \nlong -term health effects associated with COVID -19, who is affected, and why –\nand implementing vaccine recommendations to optimize protection\n▪FDA’s EUAs for COVID -19 products (including vaccines)\n▪All vaccines purchased by the U.S. government will continue to be distributed and \navailable for free\nPublic Health Emergency ending ≠ Commercialization\nCommercialization of COVID -19 Vaccines\n•Commercialization of COVID -19 vaccines is the transition of vaccines previously purchased by the U.S. Government \n(USG), to established pathways of procurement, distribution, and payment by both public and private payers\n•Timeline: Likely in early Fall\n–Considerations include what will be authorized by FDA and recommended by CDC, and what will align with a \nstrain change for potential variants\n•After commercialization, vaccines will remain free for most people through the Vaccines for Children Program, \nChildren’s Health Insurance Program, most commercial insurance, Medicare, and Medicaid programs\nhttps://aspr.hhs.gov/COVID -19/Pages/FAQ -Commercialization.aspx\n▪Vaccination equity : when everyone has fair and just access to \nvaccination.\n▪CDC works with national, state, tribal, territorial, healthcare, and \ncommunity partners to ensure all people have fair and just \naccess to vaccination.\n▪CDC uses a Social Vulnerability Index to support areas at \nincreased risk.\n▪Making sure the uninsured have continued access to COVID -19 \nvaccines with as few financial barriers as possible is a top \npriorityFocus on Vaccination Equity\n\nPharmacies Help \nIncrease Access \nto Vaccines\n\n▪HHS recently announced intent to amend the declaration under the PREP Act for \nmedical countermeasures against COVID -19.\n▪By issuing this amendment, the HHS Secretary intends to extend immunity liability to \npharmacists, pharmacy interns, and pharmacy technicians to administer COVID -19 \nand seasonal influenza vaccines through December 2024.\n▪Additional information on the planned amendment to the declaration under the \nPREP Act can be found at https://www.hhs.gov/about/news/2023/04/14/factsheet -\nhhs-announces -amend -declaration -prep -act-medical -countermeasures -against -\ncovid19.htmlPublic Readiness and Emergency Preparedness (PREP) \nAct for Medical Countermeasures against COVID -19\nInflation Reduction Act\nhttps://www.cms.gov/newsroom/fact -sheets/inflation -reduction -act-lowers -health -care -costs -millions -americans\nThe proposed Vaccines for Adults program would reduce the spread of vaccine -\npreventable diseases and pave the way to greater health equity\nVACCINES FOR \nADULTS \nPROGRAM\nVACCINE PURCHASE\nPurchase of recommended \nvaccines for all uninsured \nadults\nPROGRAM OPERATIONS\nCDC staff and systems for scientific \nand policy support, program \nmonitoring, and vaccine safety and \ndistributionPROVIDER FEES\nCovering the cost of supplies, \npatient education, storage, and \nstaffing\nPROVIDER FEE \nMANAGEMENT\nContracts to administer the provider \nreimbursement process\nVACCINE CONFIDENCE\nSupport vaccine equity through partnerships, communications, and \ntechnical assistanceAND EQUITY ACTIVITIES**These activities are funded \nin the FY24 CDC Budget with \nbase immunization funding, \nnot the newly proposed \nmandatory funding proposal \nthat would support the rest \nof these activities.\nFY24 President's Budget Request: Vaccines for Adults (VFA)\n\nLooking Forward\nContinued \nsurveillance of \nvirusesContinuing focus \non vaccine equity\nContinued vaccine \neffectiveness \nstudies\nCommunicating about \nthe Public Health \nEmergency ending\nCollaborating with \npartners on vaccine\ncommercialization\nIncreasing  \nvaccine \nconfidence", "summary": "For more information: www.cdc.gov/COVID19 COVID -19 Vaccine Program Updates Georgina Peacock, MD, MPH, FAAP Director, Immunization Services Division National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention (CDC) Overarching Objectives for the U.S. COVID -19  Vaccination Program Ensure safety and  effectiveness of  COVID -19  vaccinesReduce mortality,  morbidity, and  incidence of  COVID -19 diseaseHelp minimize  disruption to  society and  economy,…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-19-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-04-19/02-COVID-Peacock-508.pdf", "doc_date": "2023-04-19", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 13}
{"title": "03 COVID Shimabukuro 508", "content": "National Center for Emerging and Zoonotic Infectious Diseases\nmRNA COVID -19 bivalent booster vaccine \nsafety update\nAdvisory Committee on Immunization Practices (ACIP) meeting\nApril 19, 2023\nTom T. Shimabukuro, MD, MPH, MBA\nDirector, Immunization Safety Office\nDivision of Healthcare Quality Promotion \nCenters for Disease Control and Prevention (CDC)\n\nTopics\n▪Describe current data on ischemic stroke following \nmRNA COVID -19 bivalent booster vaccination \n•CDC’s Vaccine  Safety Datalink (VSD) Rapid Cycle Analysis (RCA) \nsignal assessment for ischemic stroke after Pfizer -BioNTech \nCOVID -19 mRNA bivalent booster dose vaccination in the age \ngroup ≥65 years old\n•Vaccine Adverse Event Reporting System (VAERS) data on \nischemic stroke following mRNA COVID -19 bivalent booster \ndose vaccination\n2\nVSD COVID -19 Rapid Cycle Analysis: \nAnalyses of Ischemic Stroke after Pfizer -\nBioNTech Bivalent Booster Dose\nPrepared by:\nKaiser Permanente Northern California Vaccine Study Center\nPresented by Tom Shimabukuro, MD, MPH, MBA\nCenters for Disease Control and Prevention\n3\nVaccine Safety Datalink (VSD)\n▪Established in 1990\n▪Collaborative project between CDC and 9 integrated healthcare organizations\n▪Includes electronic health record data on ~12.5 million individuals across all sites 4\nVSD RCA for bivalent boosters\n▪Pre-specified outcomes were assessed during weekly sequential \nmonitoring after COVID -19 bivalent booster vaccination*\n•Risk of pre -specified outcomes 1 –21 days following a bivalent vaccination \ncompared with bivalent vaccinated individuals who were 22 –42 days \nfollowing the bivalent dose (vaccinated concurrent comparator method)\n•All analyses adjusted for age, sex, race/ethnicity, VSD site, calendar time \n(days) and seasonality (time)\n•Signal if p -value <0.01 (1 -sided)\n* Rapid Cycle Analysis (RCA) to monitor the safety of COVID -19 vaccines in near real -time within the Vaccine Safety Datalink. Av ailable at: \nRapid Cycle Analysis (RCA) to monitor the safety of COVID -19 vaccines in near real -time within the Vaccine Safety Datalink (cdc. gov) 5\n6VSD COVID -19 vaccine RCA prespecified surveillance outcomes\nPrespecified outcomes Settings\nAcute disseminated encephalomyelitis Emergency dept, Inpatient\nAcute myocardial infarction Emergency dept, Inpatient\nAcute respiratory distress syndrome Emergency dept, Inpatient\nAnaphylaxis * Emergency dept, Inpatient\nAppendicitis Emergency dept, Inpatient\nBell’s palsy Emergency dept, Inpatient, Outpatient\nCerebral venous sinus thrombosis Emergency dept, Inpatient\nDisseminated intravascular coagulation Emergency dept, Inpatient\nEncephalitis / myelitis / encephalomyelitis Emergency dept, Inpatient\nGuillain -Barré syndrome Emergency dept, Inpatient\nImmune thrombocytopenia Emergency dept, Inpatient, Outpatient\nKawasaki disease Emergency dept, Inpatient\nMultisystem inflammatory syndrome in children/adults (MIS -C/MIS -A) Emergency dept, Inpatient\nMyocarditis / pericarditis * Emergency dept, Inpatient\nNarcolepsy / cataplexy Emergency dept, Inpatient, Outpatient\nPulmonary embolism Emergency dept, Inpatient\nSeizures/Convulsions (including 0 -7 days for youngest ages) Emergency dept, Inpatient\nStroke, hemorrhagic Emergency dept, Inpatient\nStroke, ischemic Emergency dept, Inpatient\nThrombosis with thrombocytopenia syndrome Emergency dept, Inpatient\nThrombotic thrombocytopenic purpura Emergency dept, Inpatient\nTransverse myelitis Emergency dept, Inpatient\nVenous thromboembolism Emergency dept, Inpatient, Outpatient\n*All outcomes are first ever in the ICD -10 era, except anaphylaxis which is first in 7 days, and myocarditis/pericarditis which is first in 60 days▪In COVID -19 bivalent booster vaccine monitoring, VSD RCA detected a statistical signal for ischemic stroke after \nPfizer -BioNTech bivalent booster vaccination in the age group 65 years and older\n▪No other VSD RCA pre -specified surveillance outcomes have signaled in any age groups for either of the mRNA \nCOVID -19 bivalent booster vaccines or when data for the two mRNA vaccine types are combined/pooled\nVSD investigations of an RCA signal to assess whether it \nreflects a real effect of vaccination on an outcome\n▪Data quality assessment for errors, anomalies, or missing/late -arriving data\n▪Analyses using different comparators than primary concurrent (e.g., un -boosted,\nunvaccinated or “historical” comparators) to supplement our primary analyses\n▪Additional investigations to provide context (e.g., background rates, etc.)\n▪Graphic displays of outcome incidence day by day after vaccination, using temporal scan\nstatistics to assess apparent clustering\n•Examine the temporal clustering of outcome events in subgroups defined by demographics, site or\nsimultaneous exposure (e.g., flu vaccine)\n▪If the signal is driven by a strong association in one subgroup or VSD site, further\nanalyses by site or subgroup as appropriate\n▪Chart review to confirm cases and collect additional data (e.g., date of symptom onset).\n▪Consider epidemiologic studies to further investigate surveillance findings\n7Rapid Cycle Analysis (RCA) to monitor the safety of COVID -19 vaccines in near real -time within the Vaccine Safety Datalink. Avai lable at: Rapid \nCycle Analysis (RCA) to monitor the safety of COVID -19 vaccines in near real -time within the Vaccine Safety Datalink (cdc.gov)\nVSD COVID -19 RCA analyses: \nIschemic stroke after Pfizer -BioNTech \nbivalent booster among people ≥65 \nyears of age\nCOVID -19 bivalent booster doses and influenza vaccine doses \nadministered over time among persons aged ≥65 years, by vaccine type\n9\nVSD RCA ischemic stroke definition\nICD-10 CODES TO FIND INCIDENT \nCASES  ICD-10 CODES FOR LOOKBACK TO ADJUST \nONSET DATE  (in all settings)ICD-10 CODES -TO DETECT PREVALENCE \n(history of, in all settings)                         ICD-10 CODES -OTHER CAUSE EXCLUSIONS (in all settings) \nStroke, ischemic  \n(settings = Emergency, Inpatient)Codes to adjust Stroke, ischemic onset \n(if seen within 1 day before case)Stroke, ischemic -Review for Prevalence -1ST EVER Other possible causes of Stroke, ischemic\nG45.8 Other transient cerebral \nischemic attacks and \nrelated syndromes Adjust onset date if occurs in the 1 day prior to \nincident case:Exclude if occurs EVER prior to incident case:Exclude if COVID -19 in the last 30 days prior to incident case (not \nincluding same day): \nG45.9 Transient cerebral \nischemic attack, \nunspecifiedCOVID -19 DIAGNOSIS \nI63.* Cerebral infarction Z92.82 Status post administration of tPA\n(rtPA ) in a different facility within \nthe last 24 hours prior to admission \nto current facilityZ86.73 Personal history of transient ischemic \nattack (TIA), and cerebral infarction \nwithout residual deficitsOR\nCOVID -19 POSITIVE LAB TEST\nR51.* Headache I69.* Sequelae of cerebrovascular disease Exclude if occurs in the time period noted prior to incident case \n(not including same day):\nR47.* Speech disturbances, not \nelsewhere classified I48.*Atrial fibrillation and flutter (if seen EVER prior to \nincident case)\nR29.810 Facial weakness I21.* Acute myocardial infarction  (if seen within 28 days prior \nto incident case)\nR53.1 Weakness\nS15.*Injury of blood vessels at neck level (if seen within 1 day \nprior to incident case)\nR42.* Dizziness and giddiness\nI74.*Arterial embolism and thrombosis (if seen within 1 day \nprior to incident case)\nR41.82 Altered mental status, unspecified D57.* Sickle -cell disorders (if seen EVER prior to incident case)\nR40.4 Transient alternation of awareness\nD68.5*Primary thrombophilia (if seen EVER prior to incident \ncase)\nG81.9* Hemiplegia, unspecified\nH53.9 Unspecified visual disturbance\nH53.13* Sudden visual loss\n10\nBivalent RCA concurrent comparator analyses of\nischemic strokes during a 1 –21-day Risk Interval versus \na 22–42-day Comparison Interval (data through April 8, 2023) \nNominal analysis Sequential analysis\nAge group \n(years)VaccineRisk \nevents (N)Comp \nevents (N)Adjusted \nRate Ratio95% \nConfidence \nInterval1-sided\np-valueSignal thi\nweek? \n1-sided\np <0.01s \n18–64Pfizer\nModerna49\n1852\n321.09\n0.560.73–1.63\n0.30–1.010.372\n0.981No\nNo\n65+ Pfizer 158 145 1.26 0.99–1.60 0.032 No\nModerna 80 77 1.21 0.87–1.68 0.142 No\n11\nIschemic stroke after Pfizer -BioNTech bivalent booster, age ≥65 \nyears, counts and adjusted rate ratios ( Oct 16, 2022 –April 8, 2023 )\n12 Red dot represents sequential signal: p -value <0.01 (1 -sided)RR= 1.26 (95% CI 0.99 –1.60)\n95% Age group \n(years)Interval \n(days)Comparators VaccineRisk\nevents (N)Comp\nevents (N)Adjusted \nRate RatioConfidence \nIntervalP-value\n(2-sided)\nNot bivalent65+ 1–21 Pfizer 168 2536 1.01 0.86–1.19 0.907boosted\n* Analyses only included outcomes through April 8, 2023.\n13Supplemental RCA analyses:\nIschemic strokes during the 1–21-day interval comparing bivalent boosted \nvs. un -boosted concurrent comparators (but eligible for bivalent booster )*\nCases in 1 –21-day Cases in 22 –42-day Adjusted\nAnalytic population Risk Interval Comparison Interval Rate Ratio** P-value \n(N=139) (N=108) (95% CI)\nBivalent Pfizer + same -day\nhigh-dose or adjuvanted flu 43 27 1.59 (0.99 –2.61) 0.06\nvaccine\nBivalent Pfizer + same day8 11 0.73 (0.28 –1.83) 0.50standard dose flu vaccine\nBivalent Pfizer without any107 99 1.08 (0.82 –1.42) 0.58same day flu vaccine\n14* Analyses only include vaccination data through January 14, 2023 , and stroke outcome data through Feb 25, 2023\n** Adjusted by 5 -year age groupsPost-signal analyses*:\nIschemic stroke incidence during days 1 –21 compared with days 22 –42, \namong ≥65 years with and without simultaneous influenza vaccination\nIschemic stroke following bivalent Pfizer -BioNTech mRNA \nCOVID -19 booster vaccination in people ages 65+ years\n▪Statistical signal\n•The statistical signal persisted during the November 2022 –January 2023 timeframe\n•The rate ratio has slowly attenuated from 1.92 to 1.26 and has not met signaling\ncriteria during the past 10 weekly analyses\n▪Additional signal investigation analyses\n•Supplemental analyses using un -boosted concurrent comparators showed a rate ratio\nRR=1.01 (95% CI 0.86 –1.19; p -value 0.907)\n•Analyses evaluating simultaneous high -dose or adjuvanted flu vaccine showed a rate\nratio RR=1.59 (95% CI 0.99 –2.61; p -value 0.06)\n‒Separate analyses did not detect an elevated RR for stroke after flu vaccine alone (data not shown)\n•Supplemental analyses suggest comparison interval (22 –42 days) rates were lower\nthan expected (data previously presented to ACIP February 24, 2023*)\n15*ACIP Meeting COVID -19 mRNA bivalent booster vaccine safety --February 24, 2023 (cdc.gov)\nVaccine Adverse Event Reporting System \n(VAERS)\nVAERS is the nation’s early warning system for vaccine safety\n+\nVaccine Adverse Event \nReporting System\nhttp://vaers.hhs.gov\n17\nU.S. reports to VAERS following bivalent booster COVID -19 mRNA \nvaccination among ages ≥5 years*(as of April 2, 2023) (N=28,363)\n▪Distribution by age, sex, and serious status similar regardless of manufacturer\n•Most reports (93%) were non -seriousManufacturerMedian \nAge (IQR), \nyearsMale†\nN (%)Female†\nN (%)Non -serious\nN (%)£Serious \nN (%)Doses\nadmin‡\nPfizer -BioNTech 56 (35–69) 6,599 (38) 10,580 (61) 16,124 (93) 1,307 (8) 35,256,444\nModerna 62 (45–71) 4,159 (38) 6,620 (61) 10,209 (93) 725 (7) 19,900,255\nTotal 59 (39–70) 10,758 (38) 17,198 (61) 26,331 (93) 2,032 (7) 55,156,699\n* Includes reports after Moderna bivalent booster among ages ≥6 years\n† Excludes 407 (1%) reports where sex was not reported\n£2 reports documented receipt of Moderna and Pfizer Bivalent, they are counted in each group but only counted once total\n‡Doses administered among children ages 5 –11 years vaccinated during October 18, 2022 –March 29, 2023 18\nReports to VAERS of ischemic stroke/transient ischemic attack (TIA) after \nbivalent COVID -19 mRNA vaccination in people ages ≥18 years\n(as of April 2, 2023)\n▪149 verified reports of ischemic stroke/TIA\n•Ischemic stroke ( 110), TIA ( 35), ischemic stroke + TIA (4)\n•Pfizer -BioNTech bivalent ( 112), Moderna bivalent (37)\n•Median age: 72 years (IQR: 66–79years)\n•Median time to onset: 13 days (IQR: 4 –29 days)\n•68males, 81 females\n•All verified reports (149, 100%) had at least one risk\nfactor for ischemic stroke\n‒The most common was hypertension (89, 60%)\n•Simultaneous influenza vaccination\n‒18–64 years: standard dose (6)\n‒≥65 years: high -dose (10), adjuvanted (3), standard dose (2), \nunknown type (1)Preliminary reports of ischemic \nstroke/TIA (N= 252)\nUnder review*\n(n=34)\nExcluded based \nupon chart \nreview (n= 9)\nVerified ischemic stroke/TIA by\nchart review (n= 149) *Awaiting medical records and/or healthcare provider interview; some still processing\n19Non -ischemic stroke \nverified by chart review \n(n=60)\n \n  \n   \n \n      \n       \n  \n  \n  VAERS reports and reporting rates of ischemic stroke/TIA in the 3 weeks after \nmRNA COVID -19 bivalent vaccination in people ages 18 –39, 40 –64, and ≥65 years \n(as of April 2, 2023) \nChart -verified reports Chart -verified reports Background + reports under review\nReporting rate Reporting rate Age group Obs Doses Obs Doses ExpVaccine (per million (per million † (years) reports admin* reports admin* cases doses admin) doses admin) \n18–39 Pfizer -BioNTech 3 6,334,671 0.5 3 6,334,671 0.5 88 \n18–39 Moderna 0 3,048,913 0 1 3,048,913 0.3 42 \n40–64 Pfizer -BioNTech 13 12,419,399 1.0 17 12,419,399 1.4 1,168 \n40–64 Moderna 4 7,028,873 0.6 5 7,028,873 0.7 661 \n≥65 Pfizer -BioNTech 51 13,693,161 3.7 60 13,693,161 4.4 4,993 \n≥65 Moderna 19 9,622,716 2.0 23 9,622,716 2.4 3,509 \n* Doses administered as of April 5, 2023 \n† Ramirez et al. Trends in Transient Ischemic Attack Hospitalizations in the United States. J Am Heart Assoc . 2016;5(9):e004026. (Estimated expected cases based upon observed annual incidence in 2010 for \nages 25 –44, 45 –54, and 65 –84 years, adjusted for period corresponding to 3 weeks after vaccination). 20 \nVAERS monitoring: COVID -19 mRNA bivalent booster \nvaccination and ischemic stroke \n▪No unusual or unexpected reporting patterns observed, and no\nevidence of a safety concern detected for ischemic stroke with either\nmRNA COVID -19 bivalent boosters in VAERS monitoring\n21\nSummary\nCOVID -19 mRNA bivalent booster vaccination safety –data \nfrom other monitoring systems and programs*\n▪FDA monitoring in the CMS data and Department of Veterans Affairs monitoring in the VA\nsystem have not detected any safety signals for ischemic stroke following COVID -19\nmRNA bivalent boosters using historical comparator designs\n▪Surveillance conducted by international regulatory and public health partners has not\ndetected a safety concern for ischemic stroke following bivalent COVID -19 mRNA booster\nvaccination\n▪No evidence of a safety signal for ischemic stroke in Pfizer’s global monitoring of bivalent\nCOVID -19 mRNA booster vaccination\n▪No safety signals were detected for ischemic stroke for primary series or monovalent\nboosters for Pfizer -BioNTech or Moderna COVID -19 vaccines in U.S. and global monitoring\n23*These surveillance activities did not include analyses to evaluate the effect of simultaneous flu vaccination; different\nformulations of COVID -19 mRNA bivalent booster vaccinations were used globally\nFurther evaluation and key next steps\nFurther evaluation\n▪Consult with other surveillance systems to better understand:\n•Possible role of simultaneous high -dose or adjuvanted flu vaccination with COVID -19\nvaccination\n•Possible decreased rate of stroke observed in VSD in the 3 –6 weeks following vaccination\n▪In the process of chart reviewing a random sample of 100 cases across VSD sites\n▪Continue monitoring in VAERS\nKey next steps\n▪CDC continues to recommend that everyone eligible for a COVID -19 mRNA\nbivalent booster or a flu vaccine get vaccinated\n▪CDC and FDA are engaged in epidemiologic analyses regarding simultaneous\nvaccination with COVID -19 mRNA bivalent booster and flu vaccines\n24\nAcknowledgements\n25▪CDC Immunization Safety Office\n•VAERS Team\n•V-safe Team\n•Clinical Immunization Safety Assessment\n(CISA) Project\n•Vaccine Safety Datalink (VSD) Team\n▪COVID -19 Vaccine Task Force Data Monitoring\nand Reporting Group▪Kaiser Permanente Northern California (VSD)\n▪Marshfield Clinic Research Institute (VSD)\n▪VSD sites\n•HealthPartners Institute, Minneapolis, MN\n•Kaiser Permanente Colorado, Denver, CO\n•Kaiser Permanente Northwest, Portland, OR\n•Kaiser Permanente Southern California, Los Angeles, CA\n•Kaiser Permanente Washington, Seattle, WA\n•Denver Health, Denver, CO\nDisclaimer/disclosures\n▪The findings and conclusions in this presentation are those of the presenters and\ndo not necessarily represent the official position of the CDC\n▪Mention of a product or company name is for identification purposes only and\ndoes not constitute endorsement by CDC\n▪Dr. Nicola Klein reports research support from Pfizer for COVID -19 vaccine clinical\ntrials and from Pfizer, GlaxoSmithKline, Merck and Sanofi Pasteur for unrelated\nstudies\n26\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the \nofficial position of the Centers for Disease Control and Prevention.\nPhoto credit: James Gathany \n(https://wwwn.cdc.gov/phil/\nDetails.aspx?pid=8876 ) \nExtra Slides\nIschemic stroke by day after Pfizer -BioNTech bivalent \nboosters, people ages ≥65 Years*\n*Data cutoff 2/28/2023Cluster days 13 –22, \np-value = .0637\n29", "summary": "National Center for Emerging and Zoonotic Infectious Diseases mRNA COVID -19 bivalent booster vaccine  safety update Advisory Committee on Immunization Practices (ACIP) meeting April 19, 2023 Tom T. Shimabukuro, MD, MPH, MBA Director, Immunization Safety Office Division of Healthcare Quality Promotion  Centers for Disease Control and Prevention (CDC)  Topics ▪Describe current data on ischemic stroke following  mRNA COVID -19 bivalent booster vaccination  •CDC’s Vaccine  Safety Datalink (VSD)…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-19-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-04-19/03-COVID-Shimabukuro-508.pdf", "doc_date": "2023-04-19", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 29}
{"title": "04 COVID Shimabukuro 508", "content": "National Center for Emerging and Zoonotic Infectious Diseases\nUpdate: v -safe after vaccination health checker\nAdvisory Committee on Immunization Practices (ACIP) meeting\nApril 19, 2023\nTom T. Shimabukuro, MD, MPH, MBA\nDirector, Immunization Safety Office\nDivision of Healthcare Quality Promotion \nCenters for Disease Control and Prevention (CDC)\n\nTopics\n▪Overview of v -safe\n▪Contributions of v -safe to the COVID -19 response\n▪Historical and current participation in v -safe\n▪Planning for the wind -down of the current system and \ndevelopment of next version of v -safe\n▪Continued safety monitoring of COVID -19 vaccines\n2\nOverview of v -safe for COVID -19 vaccines\n3▪Implemented December 2020\n▪Designed to collect near -real time data by direct outreach to \nCOVID -19 vaccine recipients\n•Initially conceived to rapidly collect basic safety data (local and \nsystemic reactogenicity, health impacts) at the onset of the COVID -19 \nvaccination program to provide early data while other systems, such \nas VAERS and the Vaccine Safety Datalink, were accruing data\n•Identified vaccinated pregnant persons for possible enrollment in the \nCOVID -19 Vaccine Pregnancy Registry\n•Was useful in rapidly collecting early safety data when authorizations \nand recommendations expanded to other age and risk groups (e.g., \nadditional doses for immunocompromised persons)\n•Was quickly adapted to capture simultaneous administration of other \nnon-COVID vaccines (e.g., flu vaccine)\n▪Designed, built, and supported in collaboration with Oracle \nHealth Services under a donation agreement with HHS\nOverview of v -safe for COVID -19 vaccines (continued)\n4▪Enrollment by self -registration on smartphone with any \ndependents added to guardian’s account\n▪Survey completion prompted by text message reminders for \n“health check -ins”\n▪Call follow -up to all participants who report a medically \nattended event\n▪Robust participation in its first year \n•9.3 million participants / 131 million health surveys completed\n▪Total participation to date\n•10.1 million participants / 151 million health surveys completed\nKey contributions of v -safe to COVID -19 vaccine safety\n5*V-safe identifies pregnant people for enrollment in Vaccine Pregnancy Registry | CDC\n▪V-safe has been particularly effective in characterizing the basic safety of COVID -19 vaccines during \nearly vaccine introduction and following new authorizations and recommendations\n▪V-safe successfully accomplished its mission and worked as intended\nParticipation in v -safe for COVID -19 vaccines\n6010,000,00020,000,00030,000,00040,000,00050,000,00060,000,00070,000,00080,000,00090,000,000100,000,000\n0500,0001,000,0001,500,0002,000,0002,500,000\nDec-20\nJan-21\nFeb-21\nMar-21\nApr-21\nMay-21\nJun-21\nJul-21\nAug-21\nSep-21\nOct-21\nNov-21\nDec-21\nJan-22\nFeb-22\nMar-22\nApr-22\nMay-22\nJun-22\nJul-22\nAug-22\nSep-22\nOct-22\nNov-22\nDec-22\nJan-23\nFeb-23\nMar-23New v -safe registrants by month\nNew Active Registrants Doses COVID-19 Vaccine Administered in United States\nActive registrants defined as those completing at least one survey by April 9, 2023\nDoses COVID -19 vaccine administered sourced from COVID Data TrackerDoses Registrants\nNext steps for v -safe\n7▪Timing for final registration and completing surveys will be announced soon\n▪Follow up will continue on reports of medically attended health events\n▪Next generation v -safe is under development\n•Plans to collect data on new vaccines\n•Will allow greater flexibility for surveys and use CDC IT infrastructure\n•Designed to permit longer -term support for collecting data rapidly from a large \nnumber of vaccine recipients\nCDC vaccine safety monitoring for COVID -19 vaccines\n8▪Safety monitoring and assessment of COVID -19 vaccines will continue in:\n•Vaccine Adverse Events Reporting System (VAERS)                                \nVAERS | Vaccine Safety | CDC , Vaccine Adverse Event Reporting System (VAERS) (hhs.gov)\n•Vaccine Safety Datalink (VSD)                                                                   \nVaccine Safety Datalink (VSD) | VSD | Monitoring | Ensuring Safety | Vaccine Safety | CDC\n•Clinical Immunization Safety Assessment (CISA) Project                      \nClinical Immunization Safety Assessment (CISA) Project | CISA | Monitoring | Ensuring Safety | Vaccine Safety | CDC\nCDC vaccine safety monitoring\n9▪Strong, complementary systems are in place―both new and established \nVAERS v-safe VSD CISA Project\nFull list of U.S. COVID -19 vaccine safety monitoring systems\nhttps://www.cdc.gov/coronavirus/2019 -ncov/vaccines/safety.html\nVaccine Adverse Event Reporting System (VAERS), Vaccine Safety Datalink (VSD), Clinical Immunization Safety Assessment (CISA)\nAcknowledgements\n10▪CDC Immunization Safety Office\n•V-safe Team\n▪COVID -19 Vaccine Task Force Data Monitoring and Reporting Group\n▪CDC NCEZID and DHQP Communications Teams\n▪Oracle Health Services\n▪Participants in v -safe\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the \nofficial position of the Centers for Disease Control and Prevention.\nPhoto credit: James Gathany \n(https://wwwn.cdc.gov/phil/\nDetails.aspx?pid=8876 )", "summary": "National Center for Emerging and Zoonotic Infectious Diseases Update: v -safe after vaccination health checker Advisory Committee on Immunization Practices (ACIP) meeting April 19, 2023 Tom T. Shimabukuro, MD, MPH, MBA Director, Immunization Safety Office Division of Healthcare Quality Promotion  Centers for Disease Control and Prevention (CDC)  Topics ▪Overview of v -safe ▪Contributions of v -safe to the COVID -19 response ▪Historical and current participation in v -safe ▪Planning for the…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-19-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-04-19/04-COVID-Shimabukuro-508.pdf", "doc_date": "2023-04-19", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 11}
{"title": "05 COVID Link Gelles 508", "content": "Centers for Disease Control and Prevention\nNational Center for Immunization and Respiratory DiseasesCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory DiseasesCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention \nNational Center for Immunization and Respiratory Diseases \nCOVID-19 vaccine effectiveness updates \n19 April 2023 \nRuth Link-Gelles, PhD, MPH \nLCDR, US Public Health Service COVID-19 Vaccine Effectiveness Program Lead Centers for Disease Control and Prevention \nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. \n\n        \n         \n    \n          \n       Organization of presentation \n Updates on vaccine effectiveness (VE) of monovalent vaccines against \nsymptomatic infection in children aged 6 months–4 years (Pfizer-BioNTech) \nand 6 months–5 years (Moderna) \n Update on VE of monovalent and bivalent vaccines against severe disease in \nadults with and without immunocompromising conditions \n2 \n\n     \n        \n    \n                      \n                   \n     -\n- - – — –\n–Estimates of Effectiveness of Monovalent mRNA Vaccines in Preventing \nSymptomatic SARS-CoV-2 Infection Among Children Aged 3–5 Years, \nIncreasing Community Access to Testing Program \nUpdated analyses based on: Fleming Dutra KE, Ciesla AA, Roper, LE et al. Preliminary Estimates of Effectiveness of Monovalent mRNA Vaccines in Preventing \nSymptomatic SARS CoV 2 Infection Among Children Aged 3 5 Years Increasing Community Access to Testing Program, United States, July 2022 February 2023. MMWR Morb Mortal Wkly Rep 2023;72:177 182. DOI: http://dx.doi.org/10.15585/mmwr.mm7207a3 \n3 \nPercent of people receiving COVID-19 vaccine by age and date administered \n– United States, December 14, 2020 – April 12, 2023\nhttps://covid.cdc.gov/covid-data-tracker/#vaccination-demog r aphics-trends 4\n\n      \n         \n   \n          \n      \n  \n                   \n        \n                      \n                       \n           \n                     \n    Increasing Community Access to Testing (ICATT) Program: VE of monovalent \nCOVID-19 vaccines against symptomatic infection in children aged 3-5 years \n Nationwide community-based drive-through SARS-CoV-2 testing via pharmacies \n Self-reported vaccine history at time of registration for SARS-CoV-2 testing \n Design : Test-negative, case-control analysis* \n Population : Immunocompetent children aged 3 – 4/5** years with ≥1 COVID-like \nsy\nmptom and nucleic acid amplification testing (NAAT) \n Period for analysis: \n• Tested: July 4, 2022*** – April 8, 2023, BA.4/BA.5 and XBB predominant period \n*Models adjusted for: age, gender, race, ethnicity, social vulnerability index and HHS region of the testing location, underlying conditions (presence versus absence), pharmacy \nchain conducting the test, local incidence (cases per 100,000 by individual county and state in the 7 days before test date), and date of testing. ** ICATT testing is generally limited to children ages 3 and up. ***Analysis start date depended on vaccine/dose number being analyzed: Pfizer and Moderna 1\nst doses started 7/4/2022; Pfizer 2nd dose started 7/25/2022; Moderna 2nd dose \nstarted 8/1/2022; Pfizer 3rd dose started 9/19/2022. 5 \n\nICATT: Estimates of VE for primary series monovalent Moderna vaccine (children aged \n3–5 yea\nrs) against symptomatic infection , July 4, 2022 – April 8, 2023\n6Updated from: Fleming-Dutra, Ciesla, Roper, et al. MMWR February 16, 2023.\n*Test registrants who report receiving COVID-19 vaccines are asked to report the total number of doses and manufacturer(s) of vaccines received \nand for the most recent dose, month and year of receipt; therefore, the number of months between a vaccine dose and testing is a whole number calculated as the difference between the month and year of testing and the month and year of the vaccine dose. For doses received in the same month or the month before SARS-CoV-2 testing, an additional question was asked to specify whether the dose was received ≥2 weeks before testing, and only doses received ≥2 weeks before testing were included. 17% and 21% of children who received 1 and 2 doses of Moderna, respectively, reported a prior infection >90 days before the current test.Vaccination status (months since last dose) Total testsSARS-CoV-2\npositive, N (%)Adjusted\nVE (95% CI)\nModerna, 1 dose (partial series; ages 3-5 years)\nJuly 4, 2022 – April 8, 2023\nUnvaccinated 36,779 9,801 (27) Ref\n1monovalent dose (2 weeks–1 month)* 515 107 (21) 40 (25 to 52)\nModerna, 2 doses (complete series; ages 3-5 years)\nAugust 1, 2022 – April 8, 2023\nUnvaccinated 26,856 5,972 (22) Ref\n2 monovalent doses (2 weeks–6 months)* 1,613 183 (11) 47 (37 to 54)\n2 monovalent doses (2 weeks–1 month)* 461 48 (10) 61 (47 to 71)\n2 monovalent doses (2–3 months)* 647 63 (10) 54 (41 to 65)\n2monovalent doses (4–6 months)* 505 72 (14) 18 (-6 to 37)\n20 0 20 40 60 80 100\nVaccineEffectiveness (%)-\nICATT: Estimates of VE for primary series monovalent Pfizer-BioNTech vaccine (children \naged 3–4 years) against symptomatic infection , July 4, 2022 – April 8, 2023\n7Upd\nated from: Fleming-Dutra, Ciesla, Roper, et al. MMWR February 16, 2023.\n*Test registrants who report receiving COVID-19 vaccines are asked to report the total number of doses and manufacturer(s) of vaccines received \nand for the most recent dose, month and year of receipt; therefore, the number of months between a vaccine dose and testing is a whole number calculated as the difference between the month and year of testing and the month and year of the vaccine dose. For doses received in the same month or the month before SARS-CoV-2 testing, an additional question was asked to specify whether the dose was received ≥2 weeks before testing, and only doses received ≥2 weeks before testing were included. 18%, 19% and 21% of children who received 1, 2, and 3 doses of Pfizer, respectively, reported a prior infection >90 days before the current test.\n**There was insufficient power to stratify Pfizer-BioNTech 3-dose VE estimates by time since vaccination.Vaccination status (months since last dose)Total \ntestsSARS-CoV-2\npositive, N (%)Adjusted\nVE (95% CI)\nPfizer, 1 dose (partial series; ages 3–4 years)\nJuly 4, 2022–April 8, 2023\nUnvaccinated 23,376 6,381 (27) Ref\n1 monovalent dose (2 weeks–1 month)* 448 114 (25) 20 (0 to 36)\nPfizer, 2 doses (partial series; ages 3–4 years)\nJuly 25, 2022–April 8, 2023\nUnvaccinated 18,492 4,469 (24) Ref\n2 monovalent doses (2 weeks–3 months)* 951 140 (15) 40 (28 to 50)\nPfizer, 3 doses (complete series; ages 3–4 years)**\nSeptember 19, 2022–April 8, 2023\nUnvaccinated 8,610 1,445 (17) Ref\n3 monovalent doses (2 weeks–6 months)* 478 64 (13) 27 (4 to 45)\n0 0 20 40 60 80 100\nVaccineEffectiveness (%)-2\n                \n    \n              \n         \n              \n    \n              \n          \n        \n            Limitations \n Vaccine coverage is low in children aged ≤5 years. VE estimates may be less stable when \nvaccine coverage is low. \n Prevalence of prior infection in children is high*; consequently, VE in this analysis reflects the current situation among young children in the United States. \n Low vaccination coverage in this age group may impact future ability to estimate VE, \nincluding against more severe outcomes. \n The goal of the U.S. COVID-19 vaccination program is to prevent severe disease; however, VE against symptomatic infection provides important insight into vaccine protection, \nespecially before VE estimates for key questions are available. \n*https://covid.cdc.gov/covid-data-tracker/#pediatric-seroprevalence ; 92% seroprevalence in children 6 months -17 years nationally by December 2022. 8 \n\n        \n           \n    \n           \n   \n             \n        \n         \n              \n        \n              \n   Conclusions \n Complete monovalent primary series vaccination helped provide protection for \nchildren aged 3–5 years against symptomatic SARS-CoV-2 infection for at least the \nfirst 3 months after vaccination. \n Waning of monovalent Moderna primary series appears to occur by 4–6 months \nafter the second dose. \n Initial protection and waning patterns are similar to those observed in older children \nand adults in the first months after vaccination. \n Waning of monovalent Pfizer-BioNTech VE against symptomatic infection could not \nbe assessed but is also likely based on analyses in older children and adults. \n Children should stay up to date with COVID-19 vaccines. \n CDC will continue to monitor VE in this age group, including against severe disease and for bivalent doses. \n9 \n\n     \n    \n      \n  \n                     \n                \n       - –\n— –\n–Updated estimates of bivalent VE against \nemergency department/urgent care encounters \nand hospitalizations among adults aged ≥18 years, VISION Network \nUpdated analyses based on: Tenforde MW, Weber ZA, Natarajan K, et al. Early Estimates of Bivalent mRNA Vaccine Effectiveness in Preventing COVID 19 \nAssociated Emergency Department or Urgent Care Encounters and Hospitalizations Among Immunocompetent Adults VISION Network, Nine States, September November 2022. MMWR Morb Mortal Wkly Rep 2023;71:1637 1646. DOI: http://dx.doi.org/10.15585/mmwr.mm7153a1 \n      \n    \n     \n   \n \n      \n   \n     \n \n   \n     \n       \n      \n       \n  \n      \n Cases :COVID-like illness (CLI) with \npositive PCR for SARS-CoV-2 within 14 \ndays before or 72 hours after the admission or encounter \n\n Controls : CLI with negative PCR for SARS-\nCoV-2 VISION Multi-State Network of Electronic Health Records \n Variant periods designated for \nanalysis based on time when novel sublineage became predominant at study site \n\n VE adjusted for age, sex, race, ethnicity, geographic region, calendar time, and local rates of SARS-CoV-2 circulation \n\n Vaccination documented by electronic health records and state and city registries \n11 \n\nVISION: Absolute VE of monovalent and bivalent booster against ED/U C \nencounters among immunocompetent adults aged ≥18 years, by age group –\nSeptember 2022 – March 2023*\n*Unpublished CDC data.  1\n2SARS-CoV-2- Median interval\nmRNA Dosage PatternTotal\nteststest-positive,\nN (%)since last dose,\ndays (IQR)Adjusted VE\n(95% CI)\nAged 18-64 years\nUnvaccinated (ref) 55,418 5,699 (10) -- Ref\nMonovalent doses only, last dose ≥2 months earlier 81,766 8,518 (10) 391 (311-518) 4 (0-7)\nBivalent booster, 7-59 days earlier 6,744 399 (6) 33 (20-46) 53 (48-58)\nBivalent booster, 60-119 days earlier 5,834 428 (7) 84 (71-100) 42 (35-47)\nBivalent booster, 120-179 days earlier 2,352 243 (10) 139 (129-153) 15 (2-26)\nAged ≥65 years\nUnvaccinated (ref) 10,559 1,833 (17) -- Ref\nMonovalent doses only, last dose ≥2 months earlier 42,019 5,721 (14) 343 (215-441) 20 (15-25)\nBivalent booster, 7-59 days earlier 9,103 724 (8) 35 (21-47) 61 (57-64)\nBivalent booster, 60-119 days earlier 9,086 935 (10) 86 (73-101) 47 (42-52)\nBivalent booster, 120-179 days earlier 3,857 483 (13) 139 (129-153) 25 (16-34)\n0 20 40 60 80 100Vaccine Effectiveness (%)\nVISION: Absolute VE of monovalent and bivalent booster against \nhospit\nalization among immunocompetent adults aged ≥18 years, by age \ngroup – September 2022 – March 2023*\n*Unpublished CDC data.  **Not included due to imprecise estimates (confidence intervals >50 percentage points). 13SARS-CoV-2- Median interval\nmRNA Dosage PatternTotal\nteststest-positive,\nN (%)since last dose,\ndays (IQR)Adjusted VE\n(95% CI)\nAged 18-64 years\nUnvaccinated (ref) 7,126 565 (8) -- Ref\nMonovalent doses only, last dose ≥2 months earlier 9,621 659(7) 388 (300-522) 21 (10-30)\nBivalent booster, 7-59 days earlier 839 28 (3) 33 (21-46) 68 (53 to 79)\nBivalent booster, 60-119 days earlier 746 56 (8) 84 (70-101) 27 (2 to 46)\nBivalent booster, 120-179 days earlier 268 21 (8) 137 (128-150) **\nAged ≥65 years\nUnvaccinated (ref) 6,687 1,132 (17) -- Ref\nMonovalent doses only, last dose ≥2 months earlier 20,474 2,735 (13) 354 (232-460) 25 (18 to 31)\nBivalent booster, 7-59 days earlier 35 (21-47) 64 (59 to 69) 3,494 264 (8)\nBivalent booster, 60-119 days earlier 3,561 358 (10) 86 (73-102) 53 (46 to 59)\nBivalent booster, 120-179 days earlier 1,472 158 (11) 139 (128-152) 39 (26 to 50)\n0 20 40 60 80 100\nVaccine Effectiveness (%)\nVISION: Absolute VE of bivalent booster against hosp italization among \nimmunocompromised adults aged ≥18 years –\nSeptember 2022 – March 2023*\n*Unpublished CDC data. 1\n4Median SARS-CoV-2-\nmRNA Dosage PatternTotal \nteststest-positive,\nN (%)interval\nsince last dose,\ndays (IQR)Adjusted VE\n(95% CI)\nUnvaccinated (ref) 2,763 295 (11) -- Ref\nMonovalent doses only, last dose ≥2 months earlier 9,232 977 (11) 343 (225-452) 5 (-10 to 18)\nBivalent booster, 7-59 days earlier 1,518 134 (9) 33 (19-46) 30 (12 to 44)\nBivalent booster, 60-119 days earlier 1,610 125 (8) 87 (73-102) 43 (28 to 55)\nBivalent booster, 120-179 days earlier 723 59 (8) 139 (129-152) 31 (4 to 50)\n-20 0 20 40 60 80 100\nVaccine Effectiveness (%)\n     \n       \n  \n     \n       \n          \n       \n    \n    \n      \n         \n         \n         \n         \n      \n        \n                  \n               \n          Characteristics of patients with COVID-19-associated hospitalizations, — VISION \nNetwork, 10 States, October 29, 2022–March 29, 2023 \nAll hospitalizations Critical hospitalizations* \nCharacteristic N=9499 N=1839 \nAge, median (IQR), years 75 (65–84) 74 (63–83) \nFemale sex, No. (%) 4818 (50.7) 881 (47.9) \nNo. of categories of underlying medical conditions, median (IQR)** 3 (2–4) 4 (3–5) \nImmunocompromising condition, No. (%) 1677 (17.7) 438 (23.8) \nCOVID-19 vaccination status, No. (%) \nUnvaccinated 2842 (29.9) 625 (34.0) \nComplete primary series 2273 (23.9) 451 (24.5) \nPrimary series + 1 booster dose 2388 (25.1) 445 (24.2) \nPrimary series + 2 booster doses 1320 (13.9) 218 (11.9) \nPrimary series + 3 booster doses 668 (7.0) 97 (5.3) \nPrimary series + 4 booster doses 8 (0.1) 3 (0.2) \nReceived mRNA bivalent dose*** 1567 (16.5) 269 (14.6) \n*Admitted to an intensive care unit and/or in-hospital death. \n**Categories of underlying medical conditions include pulmonary, cardiovascular, cerebrovascular, neurological or musculoskeletal, endocrine or metabolic, hematologic, renal, hepatic, and immune. \n***Any mRNA vaccine doses received on or after September 2, 2022 were considered to be bivalent. \nNote: this analysis includes recipients of mRNA or Janssen primary series \n\n    \n     \n \n                     \n                  \n  - –\n— –\n–Updated estimates of bivalent VE against \nhospitalizations among adults aged ≥65 years, \nIVY Network \nUpdated analyses based on: Surie D, DeCuir J, Zhu Y, et al. Early Estimates of Bivalent mRNA Vaccine Effectiveness in Preventing COVID 19 Associated \nHospitalization Among Immunocompetent Adults Aged ≥65 Years IVY Network, 18 States, September 8 November 30, 2022. MMWR Morb Mortal Wkly Rep 2022;71:1625 1630. DOI: http://dx.doi.org/10.15585/mmwr.mm715152e2 \n\n      \n \n     \n   \n   \n       \n        \n       \n       \n     \n     \n                          IVY Network — 25 hospitals, 20 U.S. States \n Design : Prospective, case-control \n Period : September 8, 2022–April 1, 2023 \n Population : Adults aged ≥18 years hospitalized \nw\nith COVID-like illness (CLI)* \n\n Cases: CLI and test positive for SARS-CoV-2 by RT\n-\nP\nCR or antigen test within 10 days of illness \n\n Controls: CLI and test negative for SARS-CoV-2 and \ninfluenza by RT-PCR within 10 days of illness \n\n VE adjustments: Age, sex, race and ethnicity, \nadmission date (biweekly), and HHS region \n*COVID-like illness (CLI) is defined as presence of any one of the following: fever, cough, shortness of breath, chest imaging consistent with pneumonia, new or worsening hypoxemia 17 \n\nAbsolute and relative VE against COVID-19 hospitalizations\namong immunocompetent adults aged ≥65 years — IVY \nNetwork, September 8, 2022 – April 1, 2023\n18Vaccinated Median time\nVaccinated cases, controls, since last dose, Adjusted VE,\nno./total no. (%) no./total no. (%) days (IQR) % (95% CI)\nAbsolute VE\nUnvaccinated (Ref) --\nMonovalent doses only, last dose ≥2 months earlier 783/997 (79) 884/1101 (80) 373 (259–476) 13 (-9 to 30)\nBivalent booster dose, 7–59 days earlier 61/275 (22) 175/392 (45) 34 (19–49) 65 (49–77)\nBivalent booster dose, 60–119 days earlier 105/319 (33) 183/400 (46) 89 (73–103) 43 (17–60) \nBivalent booster dose, 120–179 days earlier 73/287 (25) 92/309 (30) 141 (129–154) 22 (-26 to 52)\nRelative VE\nMonovalent doses only, last dose ≥2 months earlier (Ref)\nBivalent booster dose, 7–59 days earlier 61/844 (7) 175/1059 (17) 34 (19–49) 60 (45–71) \nBivalent booster dose, 60–119 days earlier 105/888 (12) 183/1067 (17) 89 (73–103) 35 (14–51) \nBivalent booster dose, 120–179 days earlier 73/856 (9) 92/976 (9) 141 (129–154) 17 (-21 to 42)\n-40 -20 0 20 40 60 80 100\nVaccine Effectiveness (%)\n     \n      \n    \nEstimates of monovalent VE against invasive \nmechanical ventilation and death among adults \naged ≥18 years, IVY Network  \nIVY: Effectiveness of 2-4 monovalent mRNA COVID-19 vaccine doses against \nCOVI\nD-19 invasive mechanical ventilation or death among \nimmunocompetent adults aged ≥18 years — IVY Network, February 1, 2022 –\nJanuary 31, 2023\n20Median time\nVaccinated since last Absolute \nVaccinated cases,\nno./total no. (%)controls, \nno./total no. (%)dose,\ndays (IQR)adjusted VE,\n% (95% CI)\nOverall 216/362 (60) 3080/4059 (76) 248 (138–378) 62 (52–70)\nAge group, yrs --\n18–64 85/163 (52) 1421/2095 (68) 263 (144–380) 57 (39–70)\n≥65 131/199 (66) 1659/1964 (84) 238 (133–375) 69 (57–78)\nTime since last dose to illness, days\n7–179 63/209 (30) 1112/2091 (53) 109 (68–145) 76 (66–83)\n180–364 95/241 (39) 1110/2089 (53) 269 (220–317) 54 (37–66)\n≥365 58/204 (28) 858/1837 (47) 455 (402–549) 56 (36–69)\n-20 0 20 40 60 80 100\nVaccine Effectiveness (%)\nEffectiveness of monovalent mRNA COVID-19 vaccines against COVID-19 \ninvasive mechanical ventilation or death among immunocompetent adults \naged ≥18 years — IVY Network, February 1, 2022 – January 31, 2023\n2\n1Median time\nVaccinated since last Absolute \nVaccinated cases,\nno./total no. (%)controls, \nno./total no. (%)dose,\ndays (IQR)adjusted VE,\n% (95% CI)\nTime since last dose to illness, by no. of doses \nreceived\n7–179 days before illness\n2 doses 6/152 (4) 108/1087 (10) 114 (72–153) –*\n3 doses 42/188 (22) 633/1612 (39) 116 (75–147) 70 (55–81)\n§4 doses 15/91 (17) 353/860 (41) 94 (55–135) 84 (69–92)\n≥180 days before illness\n2 doses 81/227 (36) 953/1932 (49) 418 (326–531) 50 (32–64)\n3 doses 66/212 (31) 901/1880 (48) 292 (235–366) 59 (42–72)\n§4 doses 4/80 (5) 108/615 (18) 223 (197–258) –*\n*VE estimate not reported because of insufficient sample size\n§Logistic regression models for VE of 4 monovalent doses were restricted to patients aged ≥50 years admitted during April 5, 2022–January 31, 20230 20 40 60 80 100\nVaccine Effectiveness (%)\n         \n           \n \n           \n  \n              \n     \n       \n         Limitations of VE against severe disease \n For estimates of absolute vaccine effectiveness, if unvaccinated are meaningfully \ndifferent from vaccinated individuals (e.g., by COVID-19 risk factors), estimates may \nbe biased. \n For estimates of relative vaccine effectiveness, residual protection from prior doses is \nan important consideration. \n Information on prior infection is limited, although we know rates of prior infection in the U.S. population are high. \n VE against COVID-19-associated hospitalization may underestimate protection against more severe COVID-19 disease. \n22 \n\n        \n        \n           \n             \n       \n          \n  \n             \n           \n            \n            Conclusions: updates to VE of bivalent COVID-19 boosters \n Bivalent boosters are helping provide additional protection against emergency \ndepartment/urgent care encounters and hospitalization, though evidence of \nwaning \n For most people who received monovalent doses and are eligible for a bivalent \nbooster, more than a year has elapsed since their last monovalent dose. Because of waning, they may have limited remaining protection. \n Vaccines provide durable protection against the most critical illness (mechanical ventilation and death) \n CDC will continue ongoing monitoring of VE, including for all outcomes of interest and for all authorized vaccines in the U.S. (Pfizer-BioNTech, Moderna, Janssen, Novavax) with a focus on assessing new policy recommendations and VE in \npopulations at higher risk of severe COVID-19 \n23 \n\n     \n \n \n \n \n \n \n \n \n \n \n \n \n \n    \n \n \n \n \n \n \n   \n \n Acknowledgements \nCDC COVID-19 Vaccine Effectiveness and \nPolicy Team \n Amadea Britton \n Allison Ciesla \n Monica Godfrey \n Eric Griggs \n Katherine Fleming-Dutra \n Morgan Najdowski \n Sara Oliver \n Amanda Payne \n Lauren Roper \n Laura Steinhardt \n Evelyn Twentyman \n Megan Wallace \n Ryan Wiegand VE platforms teams, including: \n Sarah Ball \n Jennifer DeCuir \n Monica Dickerson \n Margaret Dunne \n Matthew Levy \n Patrick Mitchell \n Palak Patel \n Caitlin Ray \nAn\nd many more!!!  Sarah Reese \n Zach Smith \n Diya Surie \n Zack Weber \n Mark Tenforde \n24 \n\n    \n \n      \n                           \n                          \n         For more information, contact CDC \n1-800-CDC-INFO (232-4636) TTY: 1-888-232-6348 www.cdc.gov \nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. \nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation use. No rights are implied or extended for use in printing or \nany use by other CDC CIOs or any external audiences.", "summary": "Centers for Disease Control and Prevention National Center for Immunization and Respiratory DiseasesCenters for Disease Control and Prevention National Center for Immunization and Respiratory DiseasesCenters for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention  National Center for Immunization and Respiratory Diseases  COVID-19 vaccine effectiveness updates  19 April 2023  Ruth Link-Gelles, PhD, MPH  LCDR, US…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-19-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-04-19/05-COVID-Link-Gelles-508.pdf", "doc_date": "2023-04-19", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 25}
{"title": "06 COVID Oliver 508", "content": "cdc.gov/coronavirus\nUpdates to COVID -19 vaccine policy : \nConsiderations for Future Planning\nSara Oliver, MD, MSPH\nACIP Meeting\nApril 19, 2023\nU.S. COVID -19 vaccine uptake among ages ≥12 years, \nAugust 2021 -January 2023\nSource: IZ Data Lake 01,000,0002,000,0003,000,0004,000,0005,000,0006,000,0007,000,000\nPrimary Series, Ages 12-17 Primary Series, Adults Ages 18-49 Primary Series, Adults Ages 50-64 Primary Series,  Adults Ages 65+\nBooster, Ages 12-17 Booster, Adults Ages 18-49 Booster, Adults Ages 50-64 Booster Adults Ages 65+Primary series authorization \n1stbooster authorization \n2ndbooster authorization Bivalent booster authorization Doses Administered\nCoverage / Age (years) <2 2–4 5–1112–1718–2424–4950–64>65\nAt least 1 -dose† 8.6 10.7 39.9 72.1 82.2 85.4 95.0 95.0\nCompleted primary series 4.5 5.9 32.8 61.7 66.7 72.1 83.8 94.3\nBivalent booster 0.5 0.5 4.6 7.6 7.2 11.8 21.4 42.4\nUnvaccinated 91.4 89.3 60.1 28.1 17.8 14.6 —†—†U.S. COVID -19 Vaccination Coverage (%) of Total Population by \nAge Group —April 13, 2023\n†Note: Coverage is capped at 95%\nSource: https://covid.cdc.gov/covid -data -tracker/#vaccination -demographics -trends Updated April 13 , 2023 3\nPI=Prediction Interval, VOC=Variants of Concern, VBM=Variants Being Monitored . https://covid.cdc.gov/covid -data-tracker/#variant -proportions Accessed April 18, 2023Trends in weighted variant proportion estimates & Nowcast\nUnited States, November 6, 2022 –April 15, 2023\nCollection date, week ending\nEstimated Number of Reported COVID -19 Cases by Variant \nVariant Proportions Scaled by Positive Nucleic Acid Amplification Test (NAAT) Counts\nCDC COVID -19 Lab Coordinating Unit Strain Surveillance and Emerging Variant Group. Data sources: https://covid.cdc.gov/covid -data-tracker/#variant -proportions and \nhttps://covid.cdc.gov/covid -data-tracker/#trends_newtestresultsreported_7daytestingpositive_006M\n04M\n2MPositive tests / Proportion of viral lineages\n\nWeekly population -based rates of COVID -19-associated hospitalizations \nby age group —COVID -NET, March 2020 –April 2023\nGray boxes indicate potential reporting delays. Interpretation of trends should be excluded from these weeks. \nhttps://covid.cdc.gov/covid -data -tracker/#covidnet -hospitalization -network Accessed April 13, 2023\nAge Group\nUpdates to COVID -19 vaccine policy\nCOVID -19 vaccines: \nWhere we are now COVID -19 vaccines: \nWhere we are going  Steps toward simple recommendations : \nSingle formulation for mRNA COVID -19 vaccines\nSingle (possibly annual) dose for most individuals\nFlexibility for vulnerable populations\nGoal : \nSimple\nrecommendations\n\nUpdates to COVID -19 vaccine policy\nSteps toward simple recommendations : \nSingle formulation for mRNA COVID -19 vaccines\nSingle (annual?) dose for most individuals\nFlexibility for vulnerable populations\n\nSingle formulation for mRNA COVID -19 vaccines\n▪Many monovalent COVID -19 vaccine products have already expired, others will \nexpire soon \n▪With recent update, FDA removed authorizations for monovalent mRNA COVID -19 \nvaccine products\n▪Harmonization across recommendations with bivalent mRNA COVID -19 vaccines was \ndiscussed at VRBPAC in January and at ACIP meeting in February \nSingle formulation for mRNA COVID -19 vaccines\nBenefits and Harms: Summary from previous ACIP meetings\n10▪Bivalent COVID -19 vaccines are able to induce an immune response when given \neither as a primary series or a booster dose\n–Immunogenicity data showed that a BA.1 bivalent vaccine given as a primary series induced antibody \ntiters to BA.1 that were 25 times higher than the original monovalent vaccine\n–Percentage of patients reporting solicited local or systemic events was similar to or less than percentages \nseen after original vaccine, however this may be a result of the larger percent of seropositive participants \nin the bivalent vaccine group\n▪Limited data to directly compare COVID -19 outcomes after receipt of a monovalent or \nbivalent vaccine \n–Most studies show improvement in neutralizing antibodies for Omicron variants with a bivalent vaccine\n–Bivalent vaccines expanded the immune response and provided increased diversity in antibody response\n–While unable to directly compare clinical outcomes for monovalent and bivalent vaccines in the U.S., a \nstudy in the UK found ~ 10% increase in VE for COVID -19 infections \nNumber of mRNA COVID -19 vaccine products\nModerna: 5 products\nPfizer -BioNTech: 6 products \nPreviously: \n11 TOTAL Products!\nModerna: 2 products\nPfizer -BioNTech: 3 products \nMoving forward: \n5 Products\nEliminates look -alike vials for \nModerna and Pfizer -BioNTech\nSingle formulation for mRNA COVID -19 vaccines\nSummary from February ACIP meeting\n12▪Receiving COVID -19 vaccines continues to be important for prevention of COVID -19 \nsevere disease, hospitalization, and death\n▪Many children and adolescents remain unvaccinated for COVID -19\n▪COVID -19 vaccine recommendations that are simple to implement may remove some \nbarriers to uptake\n▪Harmonizing the formulation for mRNA COVID -19 vaccines could simplify the \npresentations, reduce administration errors, and allow continued access to vaccines\n▪ACIP was supportive of a transition of the mRNA COVID -19 vaccine primary series from \nmonovalent (original) to bivalent (original plus Omicron BA.4/5)\nSingle formulation for mRNA COVID -19 vaccines\nUpdates from FDA authorizations\n13▪FDA removed the authorizations for monovalent mRNA COVID -19 vaccines\n–BLAs are still in place for monovalent products:\n•Comirnaty for ages 12 years and older, with limited doses in circulation \n•Spikevax for ages 18 years and older, but all doses are currently expired\n▪Bivalent mRNA COVID -19 vaccines are now authorized for all indications \n▪No changes to current language in other COVID -19 vaccine authorizations \n(Novavax or Janssen COVID -19 vaccines)\nSingle formulation for mRNA COVID -19 vaccines\nImplications for CDC recommendations\n14▪Transition to bivalent COVID -19 vaccines could simplify the presentations, reduce \nadministration errors, and allow continued access to vaccines with expiration of \nmonovalent products \nBivalent mRNA COVID -19 vaccines would now be recommended for all indications \nUpdates to COVID -19 vaccine policy\nSteps toward simple recommendations : \nSingle formulation for mRNA COVID -19 vaccines\nSingle (annual?) dose for most individuals\nFlexibility for vulnerable populations\n\nShifts in vaccine -induced, infection -induced, and hybrid immunity against SARS -CoV-\n2 among people aged ≥16 years —United States, Quarter 2 2021 –Quarter 3 2022\nNo infection or vaccination\nVaccine only -induced \nantibodies\nInfection only -induced \nantibodies\nBoth infection and \nvaccination -induced \nantibodies (hybrid immunity)\nSource: CDC (unpublished)\nShifts in vaccine -induced, infection -induced, and hybrid immunity against SARS -CoV-\n2 among people aged ≥16 years by age group —United States, Q2 2021 –Q3 2022\nNo infection or vaccination\nVaccination without previous \ninfection\nPrevious infection without \nvaccination\nBoth previous infection and \nvaccination (hybrid \nimmunity)\n16–29 years 30–49 years\n50–64 years ≥65 years\nSource: CDC (unpublished)\nHow frequently should people get a COVID -19 vaccine? \n▪Increases in COVID -19 cases (left) and hospitalizations (right) have occurred:\n–During the winter months and/or\n–Due to emergence of new immune escape variants\nCases from October 2021-February 2023 highlighted\nAdmissions from October 2021 –February 2023 highlighted\nhttps://covid.cdc.gov/covid -data -tracker/#trends_weeklycases_select_00 https://covid.cdc.gov/covid -data -tracker/#new -hospital -admissions\nSingle (possibly annual) COVID -19 vaccine dose\nSummary from February ACIP meeting\n▪For most older children, adolescents, and adults, future doses will be additional ‘boost’ \nafter prior infection, prior vaccination, or both\n▪Time since last COVID -19 vaccine dose may both increase the incremental benefits of a \nCOVID -19 vaccine, and decrease the risk of myocarditis \n▪Vaccine protection likely declines over time\n▪Winter months and immune escape variants have impacted COVID -19 epidemiology\n▪A simplified, annual recommendation could help reduce vaccine and message fatigue\n▪A plan for a fall booster dose could provide added protection, at a time when many \nwould be ~1 year from last dose\n–Future epidemiology and SARS -CoV-2 virus evolution could help determine the need for \ncontinued annual boosters\nSingle (possibly annual) COVID -19 vaccine dose\nUpdates from FDA authorizations\n20▪FDA authorized a single age -appropriate mRNA COVID -19 vaccine dose for most individuals\nA single age-appropriate dose of a \nbivalent Moderna COVID -19 vaccine\nis authorized for individuals \nages 6 years and older \nwho are unvaccinated , \nor at least 2 months after receipt of any \nmonovalent COVID -19 vaccine. A single age -appropriate  dose of a \nbivalent Pfizer COVID -19 vaccine\nis authorized for individuals \nages 5 years and older\nwho are unvaccinated ,\nor at least 2 months after receipt of any \nmonovalent COVID -19 vaccine\n\n63828993\n0102030405060708090100\nMar-Apr May-Jun Jul-Aug Sep-Oct Nov-DecSeroprevalence (%)\nMonth7585929799\n0102030405060708090100\nMar-Apr May-Jun Jul-Aug Sep-Oct Nov-DecSeroprevalence (%)\nMonthInfection-induced Combined (vaccine- and infection-induced) \nPediatric infection -induced and combined (vaccine -and infection -induced) \nSeroprevalence from U.S. commercial laboratories —March –December 2022\nSource: https://covid.cdc.gov/covid -data -tracker/#pediatric -seroprevalence and unpublished data (CDC) 21\nCOVID -19 vaccine recommendations in children 5 years and younger\n▪Young children likely still need a ‘ prime ’ and ‘ boost ’ to optimize immunity\n▪Young children will continue to age into the vaccine recommendations at 6 months and \ncould be SARS -CoV-2 naïve\n▪Additional data forthcoming to evaluate benefits of a multi -dose primary series in all \nchildren ages 5 years and younger, or if the recommendations could be simplified\n–Cost effectiveness analysis\n–Additional antibody data in young children \nCoverage / Age (years) <2 years 2–4 years \nAt least 1 -dose 8.6 10.7\nCompleted primary series 4.5 5.9\nUnvaccinated 91.4 89.3\nSingle (possibly annual) COVID -19 vaccine dose\nUpdates from FDA authorizations\n23▪FDA authorized one, two, or three doses of a bivalent mRNA COVID -19 vaccine for \nchildren 6 months –4 or 5 years \n▪Number of doses depend on age, as well as number and type of prior COVID -19 \nvaccine doses received \nSingle (possibly annual) COVID -19 vaccine dose\nImplications for CDC recommendations\n24▪A COVID -19 vaccine framework for a single dose could be easy for COVID -19 vaccine \nproviders to implement, and for the public to understand \n▪The current recommendations for a single dose may evolve over time, and could move \nto an annual recommendation\nA single bivalent dose would be recommended for everyone ages 6 years and older\n–For most people, this is not a change: if someone has not received a bivalent vaccine dose \nyet, they are recommended to receive one, regardless of their previous vaccine history\nChildren 6 months through 5 years would receive at least two COVID -19 vaccine doses, \nincluding at least one bivalent COVID -19 vaccine \n–Table and detailed guidance to be published in Interim Clinical Considerations\n\nUpdates to COVID -19 vaccine policy\nSteps toward simple recommendations : \nSingle formulation for mRNA COVID -19 vaccines\nSingle (annual?) dose for most individuals\nFlexibility for vulnerable populations\n\nWeekly population -based rates of COVID -19-associated hospitalizations \nby age group —COVID -NET, March 2020 –April 2023\nGray boxes indicate potential reporting delays. Interpretation of trends should be excluded from these weeks. \nhttps://covid.cdc.gov/covid -data -tracker/#covidnet -hospitalization -network Accessed April 13, 2023\nAge Group\nRates of COVID -19 deaths by vaccination status and age, adults ≥65 years  —\n24 U.S. Jurisdictions, April 2022 –January 2023\nhttps://covid.cdc.gov/covid -data -tracker/#rates -by-vaccine -status Accessed April 14, 2023 \nUnvaccinated\nVaccinated without updated booster\nVaccinated with updated boosterUnvaccinated\nVaccinated without updated booster\nVaccinated with updated boosterAges 65 –79 yearsAges ≥80 years\n▪In a January 2023 survey of adults who had previously received a bivalent booster: \n–54% said they were awaiting new guidelines for additional doses\n–86% said getting another booster shot was important or a top priorityAdditional updated COVID -19 vaccine doses \nSurvey data\nThe survey was conducted January 17 –January 24, 2023, online and by telephone among a nationally representative sample of 1,23 4 U.S. adults\nKFF COVID -19 Vaccine Monitor: January 2023. https://www.kff.org/coronavirus -covid -19/poll -finding/kff -covid -19-vaccine -monitor -january -2023/\nAccessed February 7, 2023\n 28\nCOVID -19 vaccines and older adults (adults ages ≥65 years)  \nSummary from February ACIP meeting\n▪Older adults have higher rates of hospitalization than younger adults\n▪Among older adults, vaccination rates with a bivalent COVID -19 vaccine dose remain low\n–It is important for older adults to be up to date on current recommendations, including \nreceiving a bivalent booster\n▪ACIP discussed that data were insufficient to support a routine recommendation for \nolder adults to receive a COVID -19 vaccine doses every 6 months, but acknowledged this \npopulation may continue to be more vulnerable to severe COVID -19 and likely needs \nflexibility with COVID -19 vaccine recommendations \nFlexibility for vulnerable populations \nUpdates from FDA authorizations\n30▪For adults ages ≥65 years, a single dose of a bivalent mRNA COVID -19 vaccine (either \nModerna COVID -19 Vaccine or Pfizer -BioNTech COVID -19 vaccine) may be administered \nat least 4 months following the first dose of a bivalent COVID -19 vaccine\nFlexibility for vulnerable populations \nImplications for CDC recommendations\n31▪The bivalent COVID -19 vaccine continues to provide protection against severe COVID -19 \ndisease, and rates of hospitalization or death among older adults who have received a \nbivalent booster continue to be low\n▪However, some older adults may benefit from an additional updated COVID -19 vaccine \ndose prior to possible future recommendations for updated vaccines this fall\nAdults ages 65 years and older may now choose to receive another \nupdated COVID -19 vaccine dose\n\nCOVID -19 vaccines and people who are immunocompromised \nSummary from February ACIP meeting\n▪Immunocompromised adults can have less robust immune response to COVID -19 \nvaccines\n▪There are no currently authorized prophylactic monoclonal antibody products for \npopulations at highest risk of COVID -19 \n▪ACIP discussed that data were insufficient to support a routine recommendation for \npeople who are immunocompromised to receive a COVID -19 vaccine doses every 6 \nmonths, but acknowledged this population may continue to be more vulnerable to \nsevere COVID -19 and likely needs flexibility with COVID -19 vaccine recommendations \nFlexibility for vulnerable populations \nUpdates from FDA authorizations\n33▪For persons with moderate to severely immunocompromising conditions, a single dose \nof a bivalent mRNA COVID -19 vaccine may be administered at least 2 months following \nthe first dose of a bivalent COVID -19 vaccine\n▪Additional age -appropriate bivalent mRNA COVID -19 vaccine doses may be \nadministered to immunocompromised persons at the discretion of the healthcare \nprovider, taking into consideration the individual’s clinical circumstances\nFlexibility for vulnerable populations \nImplications for CDC recommendations \n34▪For people who are immunocompromised, additional doses have been recommended \npreviously and current updates continue to allow additional protection to a vulnerable \npopulation \n▪Updates also allow flexibility to adjust to individual’s specific circumstances, including \ntiming of immunosuppression as well as the possible need for re -vaccination after \nparticular events (e.g. stem cell transplant) \n–Additional guidance to be published in Interim Clinical Considerations\nPeople who are immunocompromised may now choose to receive another updated \nCOVID -19 vaccine dose            -and-\nHave the flexibility to receive additional doses based on their clinical circumstances\n\nUpdates to COVID -19 vaccine policy\nSteps toward simple recommendations : \nSingle formulation for mRNA COVID -19 vaccines\nSingle (possibly annual) dose for most individuals\nFlexibility for vulnerable populations\nGoal : \nSimple\nrecommendations\n\nUpdates to COVID -19 vaccine policy\nSteps toward simple recommendations : \nSingle formulation for mRNA COVID -19 vaccines\nSingle (possibly annual) dose for most individuals\nFlexibility for vulnerable populations\nGoal : \nSimple\nrecommendations\nFuture a dditional steps may be possible : \nSimplifications for all COVID -19 vaccines\nPossible updated vaccines this fall \nContinue to evaluate data -driven ways to \nsimplify pediatric program\nFlexibility and simple guidance\n\n▪COVID -19 vaccines continue to be the most effective tool we have to prevent serious \nillness, hospitalization and death from COVID -19  \n▪Simple recommendations are easier to communicate, which may improve uptake\n▪Anticipate that an updated fall vaccine could be available\n▪Based on available data, anticipate benefits of COVID -19 vaccines given this fall \n–Updates to COVID -19 vaccine policy can also acknowledge possible future recommendations \n▪For most people, the current doses needed remain unchanged : a single bivalent vaccine \nis recommended and there could be an updated vaccine/recommendation this fall\n–Flexibility for vulnerable populations\n–Young children continue to be recommended for multiple doses to prime/boost immune response, \nand will continue to review additional dataUpdates to COVID -19 vaccine policy\nSteps toward simple recommendations \n▪Continue to review data and evaluate COVID -19 vaccine program in context of \nevolving epidemiology \n▪Early COVID -19 vaccine recommendations made in light of a highly susceptible, \nimmune naive population, with limited treatment options\n▪Increases in population -level immunity through both vaccine and infection, \nSARS -CoV-2 virus evolution, availability of anti -viral treatments, and review of COVID -\n19 epidemiology and hospitalization rates can lead to evidence -based updates in \nvaccine policy\n▪Work is ongoing to review additional data, continue efforts for simplification\n▪Work Group supportive of simplified recommendations as well as flexibility for \nvulnerable populations Work Group interpretation \nSteps toward simple recommendations\n▪Monica Godfrey\n▪Evelyn Twentyman\n▪Danielle Moulia\n▪Megan Wallace \n▪Hannah Rosenblum\n▪Lauren Roper\n▪Katherine Fleming -Dutra\n▪Ruth Link -Gelles\n▪Amadea Britton\n▪Sarah Meyer\n▪Julianne Gee\n▪Susan Goldstein\n▪Mary Chamberland\n▪Elisha Hall▪Valerie Morelli\n▪JoEllen Wolicki\n▪Heather Scobie\n▪Sierra Scarbrough\n▪Jefferson Jones\n▪Aron Hall\n▪Barbara Mahon\n▪Coronavirus and other Respiratory Viruses Division\n▪National Center for Immunization and Respiratory \nDiseasesAcknowledgments\nQuestion for ACIP\n40▪What are ACIP's thoughts on simplified recommendations as well as \nflexibility for vulnerable populations?\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the \nofficial position of the Centers for Disease Control and Prevention.\nThank you", "summary": "cdc.gov/coronavirus Updates to COVID -19 vaccine policy :  Considerations for Future Planning Sara Oliver, MD, MSPH ACIP Meeting April 19, 2023 U.S. COVID -19 vaccine uptake among ages ≥12 years,  August 2021 -January 2023 Source: IZ Data Lake 01,000,0002,000,0003,000,0004,000,0005,000,0006,000,0007,000,000 Primary Series, Ages 12-17 Primary Series, Adults Ages 18-49 Primary Series, Adults Ages 50-64 Primary Series,  Adults Ages 65+ Booster, Ages 12-17 Booster, Adults Ages 18-49 Booster,…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-19-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-04-19/06-COVID-Oliver-508.pdf", "doc_date": "2023-04-19", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 41}
{"title": "07 COVID Twentyman 508", "content": "Centers for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.Updates to Interim Clinical Considerations for \nUse of COVID -19 Vaccines\nEvelyn Twentyman, MD MPH\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nOverview of implications\n▪Simple and singular for most\n▪Flexible for people at higher risk\n▪Customized recommendations for young childrenImplications of the new recommendations\n▪Simple and singular for most\n▪Flexible for people at higher risk\n▪Customized recommendations for young childrenImplications of the new recommendations\nPrevious recommendations for people aged ≥6 years \nwithout immunocompromise\n\nNew recommendations for people aged ≥6 years without \nimmunocompromise who have not yet received a bivalent \nmRNA dose\nOne bivalent \nmRNA dose\nNew recommendations for people aged  ≥6 years without immunocompromise who \nhave not yet received a bivalent mRNA dose , regardless of COVID -19 vaccination \nhistory\nOne bivalent \nmRNA dose≥1 monovalent\nModerna dose\n≥1 monovalent \nNovavax dose\n≥1 monovalent \nJanssen dose\nNo COVID -19 \nvaccine doses≥1 monovalent\nPfizer -BioNTech\ndose\nNew recommendations for aged ≥6 years without \nimmunocompromise who have already received a bivalent \nmRNA dose\nOne bivalent \nmRNA dose\nVaccination is complete.\nNo doses are indicated at this time.\n▪Simple and singular for most\n▪Flexible for people at higher risk\n▪Customized recommendations for young childrenImplications of the new recommendations\nFlexible for people at higher risk of severe COVID -19:\nPeople aged ≥65 years who have not yet received a bivalent \nmRNA dose\nOne bivalent \nmRNA doseOptional additional \nbivalent mRNA dose\nAt least \n4 months\nFlexible for people at higher risk of severe COVID -19:\nPeople aged ≥65 years who have already received a bivalent \nmRNA dose\nOne bivalent \nmRNA doseOptional additional \nbivalent mRNA dose\nAt least \n4 months\n\nNew flexibility for people at higher risk of severe COVID -19:\nPeople aged ≥6 years with immunocompromise* who have \nalready received a bivalent mRNA dose\n*Including those with imminent immunocompromise (e.g., prior to organ transplant; other causes.)One bivalent \nmRNA doseOptional additional \nbivalent mRNA dose\nAt least \n2monthsAdditional \nbivalent mRNA \ndoses as needed \nAt least \n2monthsStem cell transplant\nCAR-T therapy\nB-cell depletion\nOthers\n\n▪Simple and singular for most\n▪Flexible for people at higher risk\n▪Customized recommendations for young childrenImplications of the new recommendations\nDoses previously recommended:\nModerna:\n•2monovalent primary series doses +\n•1 bivalent booster dose\nPfizer:\n•2or3monovalent primary series \ndoses +\n•1 bivalent primary series doseTransitioning from the monovalent to the bivalent era for \nchildren without immunocompromise aged 6 months –4 years\nDoses now recommended:\nCustomized by COVID -19 \nvaccination history such that all \nchildren receive:\n•At least 2 vaccine doses in total \nincluding\n•At least 1 bivalent dose\nNumber of\ndoses\nindicated, by\nmanufacturer\nVaccination complete.COVID -19 vaccination \nstatus April 2023\nPreviously received vaccine(s)COVID -19 vaccination algorithm for people without immunocompromise, ages 6 months –4 years, mRNA vaccines April 2023*\nVaccinated Unvaccinated\n1dose bivalent Moderna1dose \nmonovalent \nModerna2doses \nmonovalent \nModerna\n2doses \nbivalent \nPfizer -\nBioNTech1dose \nmonovalent \nPfizer -\nBioNTech2doses \nmonovalent \nPfizer -\nBioNTech3doses \nmonovalent \nPfizer -\nBioNTech\n1dose bivalent Pfizer -\nBioNTech2doses \nmonovalent \nModerna and 1\ndose bivalent \nModerna2doses \nmonovalent \nPfizer -BioNTech \nand 1dose \nbivalent Pfizer -\nBioNTech\n*To see product -specific doses and intervals of administration, see Table 1 and 2 forthcoming in Interim Clinical Considerations , forthcoming.2doses \nbivalent \nModernaOR3doses \nbivalent \nPfizer -\nBioNTech\nDoses previously recommended:\nModerna:\n•2monovalent primary series doses +\n•1 bivalent booster dose\nPfizer:\n•2or3monovalent primary series \ndoses +\n•1 bivalent primary series doseTransitioning from the monovalent to the bivalent era for \nchildren without immunocompromise aged 5 years\nDoses now recommended:\nCustomized so that Moderna\nrecipients receive:\n•At least 2 vaccine doses in total \nincluding\n•At least 1 bivalent dose\nAnd Pfizer recipients receive: \n•At least 1 bivalent dose\nVaccination complete.Number of\ndoses\nIndicated, by\nmanufacturerPreviously received vaccine(s)COVID -19 vaccination \nstatus April 2023 Vaccinated Unvaccinated\n1 or more doses \nmonovalent \nModerna1 or more doses \nmonovalent \nPfizer -BioNTechAny doses \nmonovalent \nPfizer -BioNTech \nand 1dose \nbivalent Pfizer -\nBioNTech2doses \nmonovalent \nModerna and 1\ndose bivalent \nmRNA\nOR2doses \nbivalent \nModerna1dose \nbivalent \nPfizer -\nBioNTech1dose \nbivalent \nPfizer -\nBioNTechCOVID -19 vaccination algorithm for people without immunocompromise, age 5 years, mRNA vaccines April 2023*\n*To see product -specific doses and intervals of administration, see reference Table 1 in Interim Clinical Considerations, forthc oming1dose \nbivalent \nModerna\n▪Adults and children aged 6 years and older are up to date with COVID -19 vaccines if they got a bivalent \n(updated) COVID -19 vaccine. \n▪Children 6 months through 5 years of age who received the Pfizer -BioNTech COVID -19 vaccine are up to \ndate if:\n–They are 6 months to 4 years of age and got at least 3 COVID -19 vaccine doses, including at least one \nbivalent (updated) COVID -19 vaccine dose. \n–They are 5 years of age and got at least 1 bivalent (updated) COVID -19 vaccine dose. \n▪Children 6 months through 5 years of age who got the Moderna COVID -19 vaccine are up to date if they got \nat least two Moderna COVID -19 vaccine doses, including at least one bivalent (updated) COVID -19 vaccine \ndose. \n▪You may be eligible for additional COVID -19 vaccine doses if: \n–You are 65 years of age and older and got your first bivalent (updated) COVID -19 vaccine booster 4 or \nmore months ago.\n–You are moderately or severely immunocompromised and received a bivalent (updated) COVID -19 \nvaccine booster 2 or more months ago.\n▪If you are unable or choose not to get a recommended bivalent mRNA vaccine, you will be up to date if you \ngot the Novavax COVID -19 vaccine doses approved for your age group. Stay Up to Date with COVID -19 Vaccines \nImplications for vaccine providers\nModerna\nPfizer -BioNTech\nNovavax\nJanssenFewer COVID -19 Vaccine Products in Use \nBivalent Bivalent\nBivalentBivalent BivalentBivalent Bivalent\nBivalent Bivalent Bivalent\nAll remaining Janssen vaccine doses \nexpire by May 6th2023Manufacturer Products Previously in Use Products Now in Use\n▪CDC’s Interim Clinical Considerations for Use of Authorized \nCOVID -19 Vaccines will be updated with comprehensive tables \nof vaccine doses and dosages indicated\n•For each age group\n•By history of COVID -19 vaccines received, for children ages 6 months \nthrough 5 years\n▪Revision of clinical guidance materials is underway\n▪COCA Call to be held May 11th, 2023*Additional help for providers is on the way\n*Please visit https://emergency.cdc.gov/coca/ for complete details\nImplications for public health\nBivalent COVID -19 vaccine coverage is low. \nCOVID -19 Data Tracker, last updated April 13, 2023, CDC COVID Data Tracker: Vaccinations in the US16.7% of the total U.S. \npopulation has received a \nbivalent COVID -19 vaccine.20.2% of adults aged \n≥18 years in the U.S. have \nreceived a bivalent COVID -\n19 vaccine.\nCOVID -19 Data Tracker, last updated April 13, 2023, https://covid.cdc.gov/covid -data -tracker/#vaccination -demographics -trends43%22%12%7%8%5%\n> 65 years50–64 years25–49 years18–24 years12–17 years5–11 years2–4 years<2 yearsBivalent COVID -19 Vaccination Coverage by AgeBivalent COVID -19 vaccine coverage generally decreases with\ndecreasing age.\nCOVID -19 Data Tracker, last updated April 14, 2023, https://covid.cdc.gov/covid -data -tracker/#vaccination -demographics -trendsBivalent COVID -19 vaccine c overage is lower among Black, non -\nHispanic, Hispanic/Latino , and Native Hawaiian or Other Pacific \nIslander .\n17%12%24%9%9%22%15%\nWhite, NHNHOPI, NHMultiracial, NHHispanic/LatinoBlack, NHAsian, NHAI/AN, NHBivalent COVID -19 Vaccination Coverage by Race/Ethnicity\nCOVID -19 Data Tracker, last updated April 14, 2023, https://covid.cdc.gov/covid -data -tracker/#vaccination -demographics -trendsBivalent COVID -19 vaccine coverage is lower among those with lower \nincome.\n39%29%27%\nAbove poverty,\nincome >$75KAbove poverty,\nincome <$75KBelow povertyBivalent COVID -19 vaccine coverage by income among adults aged ≥18 years\nCOVID -19 Data Tracker, last updated April 14, 2023, https://covid.cdc.gov/covid -data -tracker/#vaccination -demographics -trendsBivalent COVID -19 vaccine coverage is lower among those without \nhealth insurance .\n35%15%\nWith Health\nInsuranceWithout\nHealth\nInsuranceBivalent COVID -19 vaccine coverage among adults aged ≥18 years by insurance status\n▪COVID -19 vaccines continue to be the most effective tool we have to prevent serious \nillness, hospitalization and death from COVID -19 \n–Uptake of the updated (bivalent) COVID -19 vaccines is not yet equitable, and \nremains generally low\n▪Simple recommendations are easier to communicate, which may improve vaccine \nuptake\n▪CDC is continuing to work toward additional materials for vaccine providers, \nclinicians and the general public to make it easy for everyone to get up to date and \nstay up to date with COVID -19 vaccinesReflections and Next Steps\n▪Sara Oliver\n▪Hannah Rosenblum\n▪Mary Chamberland\n▪Susan Goldstein\n▪Elisha Hall\n▪JoEllen Wolicki\n▪Katherine Fleming -Dutra\n▪Ruth Link -Gelles\n▪Monica Godfrey\n▪Danielle Moulia\n▪Megan Wallace \n▪Lauren Roper\n▪Amadea Britton\n▪Sarah Meyer\n▪Julianne Gee▪Heather Scobie\n▪Sierra Scarbrough\n▪Yvonne Bolen\n▪Jefferson Jones\n▪Noelle Molinari\n▪Aron Hall\n▪Barbara Mahon\n▪Data Analytics and Visualization Task Force\n▪Coronavirus and other Respiratory Viruses \nDivision\n▪Immunization Services Division\n▪National Center for Immunization and Respiratory \nDiseasesAcknowledgments\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position o f the Centers for Disease Control and Prevention.\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation use. No rights are implied or extended for use in printing or \nany use by other CDC CIOs or any external audiences.\nAdditional Flowcharts\nVaccination complete. Optional additional doses as needed**Previously received vaccine(s)\nNumber of \ndoses \nIndicated, by \nmanufacturer COVID -19 vaccination \nstatus April 2023\n1 or more\ndoses \nmonovalent \nModerna2dose \nmonovalent \nPfizer -BioNTech \nand 1dose \nbivalent mRNA2doses \nmonovalent \nModerna and 1\ndose bivalent \nmRNA\n1dose bivalent Moderna\n1dose bivalent Pfizer -BioNTechOR1 or more\ndoses \nmonovalent \nPfizer -\nBioNTechVaccinated UnvaccinatedCOVID -19 vaccination algorithm for people who are NOT moderately or severely immunocompromised, age 6 years and older, mRNA vacc ines April 2023*\n*To see product -specific doses and intervals of administration, see reference Table 1 in Interim Clinical Considerations, forthcoming. \n**People ages 65+ have the option to receive 1 additional bivalent mRNA dose at least 4 months after the first dose of a biva lent mRNA vaccine. \nTables\nCOVID -19 vaccination history Bivalent vaccine Number of bivalent \ndoses indicatedDosage (mL/ug) Vaccine vial cap and label colors Interval between doses\nUnvaccinatedModerna\n___or___20.25 mL/25 ug Dark blue cap; gray label borderDose 1 and Dose 2: \n4–8 weeks\nPfizer BioNTech30.2 mL/3 ug MaroonDose 1 and Dose 2:\n3–8 weeks\nDose 2 and dose 3:\nAt least 8 weeks\n1 dose monovalent Moderna Moderna 1 0.25 mL/25 ug Dark blue cap; gray label border 4-8 weeks after monovalent dose\n2 doses monovalent Moderna Moderna 1 0.2 mL/10 ug Dark pink cap; yellow label border At least 8 weeks after last monovalent dose\n2 doses monovalent Moderna \nand 1 dose bivalent Moderna NA; previously received 1 \nbivalent vaccine dose NA NA NA NA\n1 dose monovalent Pfizer -\nBioNTechPfizer BioNTech 2 0.2 mL/3 ug MaroonDose 1: 3 –8 weeks after monovalent dose\nDose 1 and Dose 2: At least 8 weeks \n2 doses monovalent Pfizer -\nBioNTechPfizer BioNTech 1 0.2 mL/3 ug Maroon At least 8 weeks after last monovalent dose\n3 doses monovalent Pfizer -\nBioNTechPfizer BioNTech 1 0.2 mL/3 ug Maroon At least 8 weeks after last monovalent dose\n2 doses monovalent Pfizer -\nBioNTech and 1 dose bivalent \nPfizer -BioNTechNA; previously received 1 \nbivalent vaccine doseNA NA NA NATable 1. COVID -19 vaccination schedule for people who are NOT moderately or severely immunocompromised \nby COVID -19 vaccination history, April 2023 :Ages 6 months –4 years\nCOVID -19 vaccination history Bivalent vaccine Number of bivalent \ndoses indicatedDosage (mL/ug) Vaccine vial cap and label colors Interval between doses\nUnvaccinatedModerna\n___or___20.25 mL/25 ug Dark blue cap; gray label borderDose 1 and Dose 2: \n4–8 weeks\nPfizer BioNTech 1 0.2 mL/10 ug Orange\n1 dose monovalent Moderna Moderna\n___or___1 0.25 mL/25 ug Dark blue cap; gray label border 4–8 weeks after monovalent dose \nPfizer BioNTech 1 0.2 mL/10 ug Orange At least 8 weeks after monovalent dose \n2 doses monovalent Moderna Moderna\n___or___1 0.2 mL/10 ug Dark pink cap; yellow label border At least 8 weeks after last monovalent dose\nPfizer BioNTech 1 0.2 mL/10 ug Orange At least 8 weeks after last monovalent dose \n2 doses monovalent Moderna \nand 1 dose bivalent mRNA NA; previously received \n1 bivalent vaccine doseNA NA NA NA\n1 or more doses monovalent \nPfizer -BioNTech Pfizer -BioNTech10.2 mL/10 ug Orange At least 8 weeks after last monovalent dose \n2 doses monovalent Pfizer -\nBioNTech and 1 dose bivalent \nPfizer -BioNTechNA; previously received \n1 bivalent vaccine dose NA NA NA NATable 1. COVID -19 vaccination schedule for people who are NOT moderately or severely immunocompromised \nby COVID -19 vaccination history, April 2023 :Age 5 years", "summary": "Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-19-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-04-19/07-COVID-Twentyman-508.pdf", "doc_date": "2023-04-19", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 35}
{"title": "Mpox 01 Sanchez 508", "content": "National  Center  for  Emergin  g and  Zoonoti  c Infectiou  s Diseases\nMpox Vaccine Work Group \nPablo Sanchez MD \n*he +hio State ,ni-ersity.Na/on0ide Children1s 2ospital \nChair, ACIP Mpox Work Group \nACIP Meeting \nFebruary 22, 2023 \n  \n   \n      \n       \n     \n     \n         \n  \n         \n      Mpox – 2istorical Context \n   \n– – \n \n– \n– \n– R are, sometimes life-threatening infection \nEndemic in parts of west and central Africa \nCaused by monkeypox virus (which is an orthopoxvirus) \nC\nlade I (previously Congo Basin Clade) \nClade II (previously West African Clade) \nCan spread from infected animals to people and then person-to-person \nR espiratory secretions \nSkin-to-skin contact with infected bodily fluids (e.g., fluid from lesions) \nFomites (e.g., shared towels, clothing, and bedding) \n\n     \n   \n  \n   \n   \n   \n \n    \n     \n  \n   \n  \n   \n   \n  \n  \n  \n   \n                \n                \n               Timeline of Notable Human Mpox Events* \n-First human case \nidentified -Rural settings US outbreak from pet prairie dogs (cohoused with infected small mammals from Ghana): 47 cases Outbreak in Nigeria involving 17 states: 138 cases Multinational outbreak \nImported cases to UK and Israel: 3 Imported cases to UK, Singapore: 2 Imported human cases to UK and US: 3 \n1970 2003 2017 2018 2019 2021 2022 \n*During 1970-2021, mpox was known to be endemic in 9 African countries: Cameroon, Central African Republic, \nCote d’Ivoire, Democratic Republic of Congo, Gabon, Liberia, Nigeria, Republic of Congo, and Sierra Leone; during recent years, there has been a re-emergence of human cases after decades of no reported cases \n\n \n  \n        \n     \n        \n \n       \n        \n          \n                   \n      Person-to-person spread \n Historical outbreaks in Africa \n– Associated with close skin-to-skin contact and contact with fomites \n– Zoonotic exposure cause of most cases \n– Few secondary cases among close contacts (e.g., household contacts) \n US outbreaks \n– 2003: No secondary cases  no vaccinations offered \n– 2021: No secondary cases  ACAM2000 offered to some contacts* \n– 2022: Many secondary cases >1 million doses of JYNNEOS administered \n*ACAM2000 was offered through a CDC Investigational New Drug Protocol that allows for vaccination after mpox exposure. Only contacts with high-\nrisk exposures were offered vaccine; none accepted. \n\n   \n         \n       \n   \n    2021 ACIP Orthopoxvirus Vaccine Vote \n Use of orthopoxvirus vaccine, JYNNEOS, (licensed in 2019) for pre-exposure \nvaccination of people at occupational risk for orthopoxvirus exposures \n 2-dose series, subcutaneous administration \n Recommendations published June 3, 2022* \n*https://www.cdc.gov/mmwr/volumes/71/wr/mm7122e1.htm \n\n        \n Currently no ACIP recommendation for use of JYNNEOS \nduring outbreaks \n\n    \n   \n    \n    \n        \n           \n       \n      \n     \n        \n        \n \n       \n     \n       \n        \n         \n        \n        \n       \n  Current U.S. national mpox vaccination strategy* \nVaccination  befor  e exposur  e to  \nmpox virus Post-exposur  e prophylaxis \n-Gay  , bisexual  , and  other  MSM  , transgender  or  \nnonbinar  y people  (including  adolescents  who  fal l into  \nthe  aforementioned  categories)  who  in  the  pas t 6  \nmonths  have  had: -People who are known contacts to someone \nwith mpox and identified by public health authorities (for example, via case investigation, \ncontact tracing, or risk exposure assessment) \n• New diagnosis of ≥ 1 sexually transmitted disease -People who are aware that a recent sex \n• More than one sex partner partner within the past 14 days was diagnosed \n-People with the following in the last 6 months: with mpox \n• Sex at commercial sex venue -Gay, bisexual, or other MSM, and transgender \n• Sex  in  a\nssociation  with  large  public  even  t in  \ngeographic  area  where  mpox  transmission  is  \noccurring or no\nnbinary people (including adolescents \nwho fall into any of the aforementioned \ncategories) who have had any of the following \n-Sexua  l partners  o f people  with  the  above  risks wit\nhin the past 14 days: sex with multiple \n-People  who  a nticipate  experiencing  above  risks\n-People  with  HI V o r othe  r causes  o f \nimmunosuppression  who  have  had  recen  t or  \nanticipate  potentia  l mpox  exposure par\ntners (or group sex); sex at commercial sex \nvenue; or sex in association with an event, venue, or defined geographic area where mpox \n transmission is occurring \n*https://www.cdc.gov/poxvirus/monkeypox/interim-considerations/overview.html \n\n       \n  \n        \n   \n     \n          U.S. strategy for vaccination with JYNNEOS during \ncurrent outbreak \n Intradermal preferred but subcutaneous can be administered for persons \naged ≥ 18 years \n Subcutaneous for persons aged <18 years* \n 2-dose series with second dose administered 1 month after first dose \n*https://www.cdc.gov/poxvirus/monkeypox/interim-considerations/overview.html \n\n      \n \n \n                Tentative timeline for ACIP discussions and votes* \nMpo  x outbreaks  : Use  o f 2-dose  JYNNEOS \nfor  person  s age  d <1  8 year  s \n-Update  s abou  t vaccine  effectivene  ss an  d \nsafety Mpo  x outbreaks  : Use  o f 2\ndose  JYNNEOS  for  persons\nage  d ≥  18  years - Consider  n ee  d for  longer  ter  m \nvaccinatio  n strateg  y for  2-dose  \nJYNNEOS  \nFebruar  y 2023 June 2023 October  2 023 \n*February 2023 and June 2023 votes do not impact existing recommendations for the current mpox outbreak. \nD https://www.cdc.gov/poxvirus/monkeypox/interim-considerations/overview.html \n\n    \n    \n   \n                Tentativ  e timeli  ne fo  r ACI  P discussio  ns  and votes* \n       Current US mpox vaccination strategy remains active: Populations\nCurrent   U.S.  mpox vaccinati  on strategy  re mai n at high risk should continue to be vaccinated. s in effect  \nFebruar  y 2023 June  2023 October  2 023 \n*February 2023 and June 2023 votes do not impact existing recommendations for the current mpox outbreak.\nD https://www.cdc.gov/poxvirus/monkeypox/interim-considerations/overview.htmlMpox outbreaks: Use of 2 -\ndose JYNNEOS for persons \naged ≥ 18 years Mpo  x outbreaks  : Use  o f 2-do se  JYNNEOS \nfor  person  s age  d <1  8 year  s \n-Update  s about  vaccine  effectivene  ss an  d\nsafety    Consider need for longer \n   term vaccination strategy \nfor 2-dose JYNNEOS \n \n\n   \n    \n   \n    \n    \n   \n    \n       \n       \n Goal for today’s meeting \n Updates from the ongoing outbreak \n– Epidemiology: Sascha Ellington \n– Vaccine effectiveness: Anna Chard \n– Vaccine safety: Jonathan Duffy \n– Community engagement: Kevin Delaney \n– Equity and implementation: Rosalind Carter \n Discuss use of 2-dose JYNNEOS (subcutaneous) during mpox outbreaks \n– Evidence to recommendations (EtR) framework: Agam Rao \n– ACIP vote \n\n    \n         \n        \n       \n                \n                \n                 \n     Proposed wording for today’s vote \nACIP recommends the 2-dose* JYNNEOS vaccine series for persons \naged 18 years and older at risk of mpox during an mpox outbreak§ \n*Dose 2 administered one month after dose 1 \n§ Public health authorities determine whether there is an mpox outbreak; a single case may be considered \nan mpox outbreak at the discretion of public health authorities. Other circumstances in which a public \nhealth response may be indicated include ongoing risk of introduction of mpox into a community due to \ndisease activity in another geographic area. \n\n \n \n  \n    WG members \nACIP Member \nPablo  Sánchez \nBeth Bell \nEx Officio and Liaison Members \nCSTE:  Chris  Hahn  / Paul  Cieslak \nASTHO: Ericka McGowan \nN\nACHO: Philip  Huang \nFDA:  Sixun  Yang,  Clemen  t \nMeseda &  A lonzo  García \nACOG: Howard  Minkoff \nAAP: Jim Campbell AIM:  Rob Schechter /  Jane  Zucker \nAPHL  :  J afar Razeq \nNIH:  Janet  Lathey / Kimberly  Taylor  \nIHS: Matthew Clark \nNACI:  Nicole Forbes  / Oliver  Baclic \nIDSA:  Shireesha Dhanireddy /  Rajesh Gandhi \nInvite  d Consultants \nSubject  matter  experts: Inger  Damon,  Stuar  t \nIsaacs,  Mike  Merchlinsky &  Amanda  \nZarrabian (HHS/BARDA) Clinician  experts  in STIs,  HIV, pediatrics  , \nmaternal  vaccination,  vaccine  safety,  health  \nequity,  smallpox  vaccination  strategies  , \noccupational  health \n\n \n   \n  \n    \n   Clinician experts \nSTIs, HIV, and mpox \n(adult and peds): Jason  Zucker \nJ\neanne  Marrazzo \nP\nablo  Tebas \nVince Marconi \nKim Workowski \nBonnie Maldonado \nImmu\nnizations (including for special \npopulations) and vaccine safety: Ruth Karron \nF\nlor Munoz-Rivas \nK\nathy Edwards Health  eq uity,  vaccination  strategi  es \nincludin  g fo  r smallpox: \nJoel Breman \nGerard Vong \nO\nccupational  Med icin  e and  work  er safety: \nMark  Russi \n\n \n     \n   \n  \n \n    \n \n  \n \n \n  \n  \n \n \n \n   \n \n    \n CDC contributors \nMpox epi, lab, and vaccine experts \nBrett  P etersen Andrea  Mc\nCollum \nChristy  Hutson \nLaborator  y Respons  e Network: \nJulie  Villanueva \nInf\nection control, worker safety: \nMarie de Perio David Kuhar \nSpecial populations (e.g., Persons \nexperiencing homelessness) Emily Mosites Vaccine safety \nMichael  McNeil \nJonathan  Duffy \nR\negulatory Affairs \nYon Yu \nSTIs and HIV \nLaura  Bachmann \nLeandro  Mena \nJohn  Brooks  \nA\nlexa Oster Dr ug Services \nJulian Jolly \nVaccine \nimplementation \nL\niz Velasquez \nJames  Lee \nDo\nD Liaison to CDC \nAlan Lam \nWork group lead \nAgam Rao \n\n    \n \n      \n                  \n          Thank you! \nFor more information, contact CDC \n1-800-CDC-INFO (232-4636) TTY: 1-888-232-6348 www.cdc.gov \nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.", "summary": "National  Center  for  Emergin  g and  Zoonoti  c Infectiou  s Diseases Mpox Vaccine Work Group  Pablo Sanchez MD  *he +hio State ,ni-ersity.Na/on0ide Children1s 2ospital  Chair, ACIP Mpox Work Group  ACIP Meeting  February 22, 2023                                                                 Mpox – 2istorical Context      – –    –  –  – R are, sometimes life-threatening infection  Endemic in parts of west and central Africa  Caused by monkeypox virus (which is an orthopoxvirus)  C lade…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/Mpox-01-Sanchez-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 16}
{"title": "Mpox 02 Ellington 508", "content": "Epidemiology  of Mpo  x \nduring  the Curre  nt \nOutbreak\n \nSascha  Ellington,  PhD,  MSPH \nEpidemiology  Task  Force \n2022  Multinational  Mpox  Response   \nCenters  for Disease  Control  and  Prevention \nFebruary  22, 2023 \n    Epidemiology of the Current Outbreak \n21 \n     \n      \n \n     \n \n      \n   \n      \n      \n      \n       \n    \n   \n   \n     en\nl,\nn2022-2023 Spread of Mpox in U.S. \n• The first U.S. case was confirmed in \nMay 2022. \n• At first, spread was associated with \ninternational travel. \n• More than 30,000 U.S. cases have be reported; new cases are declining. \n• Most cases have been in gay, bisexua \n& other men who have sex with men. \n• Cases have also been reported in me who do not have sex with men, \ncisgender and transgender women, \ntransgender men, gender-diverse \npeople, children, and teens. \nData as of February 8, 2023 \n        \n U.S. Mpox Case Trends as of February 9, \n2023 \n\n        \n      *   Sex / Gender Cases Percent \n Cisgender men 28,010 95.1% \n Cisgender women 854 2.9% \n Transgender men 76 0.3% \n Transgender women 266 0.9% \n Another sex/gender 235 0.8% \n Missing gender 728 -\n      Mpox cases reported to CDC by age and \nsex/gender \n*Sex/Gender is available for 97.6% of cases \nData as of February 8, 2023 \nMedian Min Max \n34 < 1 89 \n        \n       \n   \n  \n \n \n   \n \n   \n  \n        \n    \n     Mpox cases reported to CDC by race and \nethnicity \nRace / Ethnicity*+ Count Percent \nBlack or African \nAmerican 9,331 33.1% \nHispanic or Latino 8,773 31.1% \nWhite 8,258 29.3% \nAsian 789 2.8% \nOther Race 690 2.4% \nMultiple Races 151 0.5% \nAmerican Indian or Alaska Native (AI/AN) 111 0.4% \nNative Hawaiian or Other Pacific Islander 68 0.2% \n(NH/OPI) \nMissing 1,998 -\n*All cases reporting Hispanic ethnicity are classified into \nthe Hispanic or Latino category \n+Race/Ethnicity available for 93.4% of cases \nData as of February 8, 2023 \n     \n      \n \n \n  \n \n   \n  \n  \n    \n \n \n        \n           \n    \n    \n Clinical Characteristics of Mpox Cases \nReported to CDC as February 9 , 2023 \nCharacteristic Percentage \nHIV Status* \nHIV Positive 53% \nHIV Negative 47% \nRash location** \nGenitals or perianal area 65% \nTrunk or limbs 62% \nHead, face, mouth 54% \nPalms or soles of feet 24% \nHospitalized Yes 7.7% \nNo 92% \n*HIV status available for 9,039 (30%) of mpox cases \n**Rash location available for 14,902 (49%) of mpox cases 32 mpox associated \ndeaths (0.1% of all cases) reported in the U.S. \n    \n    \n        \n      \n  \n       \n  \n  \n          \n  \n            Detection and transmission of mpox \nduring the current outbreak \n• Spread primarily through sexual or close intimate contact \n• Other routes of transmission have been reported \n Household transmission \n Injury with contaminated sharp instrument in clinical setting \n Piercing and tattooing \n Perinatal transmission \n• Some people can spread mpox virus to others 1-4 days before symptom onset reported (i.e. pre-symptomatic transmission) \n• No evidence that people who are infected but never develop symptoms can spread mpox \nhttps://www.cdc.gov/poxvirus/monkeypox/about/science-behind-transmission.html \n    \n    \n        \n          \n  \n  \n \n \n    \n  \n  \n  \n   \n   \n                           \n                                \n     \n       Detection and transmission of mpox \nduring the current outbreak \nMpox Virus in Human Samples and Implications for Transmission \nExposure source Mpox virus DNA detected by PCR Replication-competent virus \ndetected/isolated Epidemiologically supported source of infection \nSkin Yes Yes Yes \nOropharynx and saliva Yes* Yes Yes \nAnorectum Yes Yes Yes† \nSemen Yes* Yes Insufficient data \nUrine/urethra Yes Yes Insufficient data \nConjunctivae or ocular fluid Yes Yes Insufficient data \nBlood/plasma/serum Yes Insufficient data Insufficient data \nFeces Yes Insufficient data Insufficient data \nVagina Yes Insufficient data Insufficient data† \nBreastmilk Insufficient data Insufficient data Insufficient data \nContaminated sharp‡ Insufficient data Insufficient data Yes \n* DNA has been detected at Ct values <35 in recovered patients more than 30 days after illness onset in an upper respiratory tract swab, saliva, and semen. \n† The preponderance of existing data support exposure to anorectal and vulvovaginal tissues and %uids as capable of transmitting infection; however, it is difficult with current evidence to definitively isolate these exposures \nfrom other concomitant exposures (see text). \n‡ Includes body modi+cation with piercings and tattooing. \nhttps://www.cdc.gov/poxvirus/monkeypox/about/science-behind-transmission.html \n        \n  \n      MMSC* among \nMen** Cases Percent \n  Men, recent MMSC 14,143 75.4% \n   Men, no recent MMSC 4,612 24.6% \nMissing 9,331 -\n   \n \n    \n     Mpox cases among men reported to CDC by \nsexual contact history \n*MMSC= male-male sexual contact \n**Sexual contact history and gender \navailable for 66.8% of cases among men \nData as of February 8, 2023 \n\n     \n Epidemiology of Mpox in Less Affected \nPopulations \n30 \n       \n    \n Percentage  among  \nCisgender  wom  en \n(n=769) Characteristic \nAge \n Median (Range)  32 (15–89) \n  Race and ethnicity \n Black, non-Hispanic 44% \n White, non-Hispanic 25% \n Hispanic or  Latino 23% \n HIV Status* \n  HIV positive 8% \n HIV  negative 92% \n     Recent sexual or close intimate partner** 71%     \n   \n  \n Mpox in Cisgender Women in the United \nStates, May 11–November 7, 2022 \n2.7% of all cases \nreported to CDC were among cisgender women \n*HIV  status  available  for 17 3 (22%)  cisgender  women \n**Define  d as within  last 3 weeks;  data  available  for  463 (60%)  cisgender  women \nSource: http://dx.doi.org/10.15585/mmwr.mm7201a2 \n      \n   \n               \n                \n              \n          \n      \n              \n     \n \n         \n         \n                \n               \n    \n Mpox in Pregnant and Recently Pregnant \nPeople in the U.S. \n• From May 11-November 7, 2022, 21 cases of mpox reported to CDC occurred in pregnant \npeople and 2 reported cases occurred in people who were recently pregnant (within 3 weeks of delivery) \n• Among those with exposure data (n=12): 9 with sexual contact and 3 with household contact \n• Similar signs and symptoms of mpox as those in non-pregnant people \n 4 cases with genital lesions during pregnancy \n• Tecovirimat provided to 48% of people with mpox during pregnancy with no adverse events \nreported \n• None received post-exposure prophylaxis with JYNNEOS \n• Outcomes \n Four hospitalizations for mpox indications. All discharged while still pregnant. \n No pregnant patients required intensive care, intubation, or unplanned delivery \n 3 pregnancy outcomes: 2 uncomplicated live births (no transmission to the infant); 1 first trimester spontaneous \nabortion \n Two recently pregnant persons experienced symptoms within 3 days of delivery and their newborns developed lesions within a week \nSource: http://dx.doi.org/10.15585/mmwr.mm7201a2 \n     \n      \n  \n  \n \n  \n  \n \n \n  \n \n  \n  \n    \n Percentage among \ntransgender and gender-\nCharacteristic diverse persons \nAge \nMedian (Range) \nRace and ethnicity \nBl\nack, non-Hispanic \nWhite, non-Hispanic \nHispanic or Latino \nHIV Status \nHIV positive \nHIV negative \nRecent sexual or close \nintimate partner 32 (18–71) \n28% \n28% \n37% \n48% \n52% \n84% \n          \n             \n       \n    \n         Mpox in Transgender and Gender-Diverse \nAdults — United States, May 17–November 4, 2022 \nGender identity of transgender and \ngender-diverse adults with mpox (n=466) \n43% \n15% 42% Transgende  r women \nTransgende  r men \nGender-divers  e persons \n96% of gender-diverse adults were assigned male sex at birth. \nSource: http://dx.doi.org/10.15585/mmwr.mm715152a1 *HIV status available for 166 (36%) transgender and gender-diverse adults \n**Defined as within last 3 weeks; data available for 378 (80%) transgender and gender-\ndiverse adults \n     \n      \n     \n      \n  \n \n  \n \n  \n     \n      \n \n   \n \n %by age group, yrs \n0–4 5–12 13–17 \nCharacteristic (n =16) (n =12) (n =55) \nSex \nMale 75% 50% 89% \nFemale 25% 50% 11% \nRace or ethnicity \nBlack, non-Hispanic 44% 42% 49% \nHispanic or Latino 31% 42% 34% \nWhite, non-Hispanic 19% 17% 9% \nAsian, non-Hispanic — — 4% \nAmerican Indian or Alaska Native, non-Hispanic — — 2% \nNative Hawaiian or other Pacific Islander, non-Hispanic 6% — — \nOther, non-Hispanic — — 2% \nExposure setting and route \nSexual contact — — 97% \nHousehold contact 93% 100% — \nOther 7% — 3% Epidemiologic Characteristics of Pediatric Cases \nin the U.S., May 17–September 24, 2022 \nSource: http://dx.doi.org/10.15585/mmwr.mm7144a4 \n  Vaccine Administration \n35 \n     \n       \n           \n120,000Doses administered 100,000 \n80,000 \n60,000 \n40,000 \n20,000 \n0 Total JYNNEOS Vaccine Doses Administered \nand Reported to CDC by week \n1,185,907 doses administered and reported to CDC since May 20, 2022 \nFirst doses \nSecond doses 5/22-5/28 \n5/29-6/4 \n6/5-6/11 \n6/12-6/18 \n6/19-6/25 \n6/26-7/2 \n7/3-7/9 \n7/10-7/16 7/17-7/23 \n7/24-7/30 \n7/31-8/6 \n8/7-8/13 \n8/14-8/20 \n8/21-8/27 \n8/28-9/3 \n9/4-9/10 \n9/11-9/17 \n9/18-9/24 \n9/25-10/1 \n10/2-10/8 \n10/9-10/15 \n10/16-10/22 10/23-10/29 \n10/30-11/5 \n11/6-11/12 \n11/13-11/19 \n11/20-11/26 \n11/27-12/3 \n12/4-12/10 \n12/11-12/17 \n12/18-12/24 \n12/25-12/31 \n1/1-1/7 \n1/8-1/14 \n1/15-1/21 \n1/22-1/28 \n1/29-2/6 \n     Data as of February 7, 2023 \n       \n \n     Mpox Cases and Vaccine Recipients by Race \nand Ethnicity \n100% 0.2% \n90% \n80% 70% 60% \n50% \n40% \n30% 20% 10% \n0% 2.4% \n2.8% \n29% 0.4% \n0.5% 2.7% \n3.6% 0.3% \n0.4% \n7.3% \n52% \n31% \n22% \n33% \n13% \nMpox Cases (N=28,171*) Mpox Vaccine Recipients** (N=704,728) Nativ  e Hawaiia  n or  Other  Pacific \nIslander \nAmerica  n India  n or  Alaska  Native \nMultipl  e Races \nOthe  r Race \nAsian \nWhite Hispani  c o r Latino \nBlac  k o r Africa  n American \n         \n                 *\nRace and ethnicity available for 93% of mpox cases reported \n**Based on 1st dose; Data as of February 9, 2023; race and ethnicity available for 91% of first doses administered", "summary": "Epidemiology  of Mpo  x  during  the Curre  nt  Outbreak   Sascha  Ellington,  PhD,  MSPH  Epidemiology  Task  Force  2022  Multinational  Mpox  Response    Centers  for Disease  Control  and  Prevention  February  22, 2023      Epidemiology of the Current Outbreak  21                                                                                   en l, n2022-2023 Spread of Mpox in U.S.  • The first U.S. case was confirmed in  May 2022.  • At first, spread was associated with  international…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/Mpox-02-Ellington-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 18}
{"title": "Mpox 03 Duffy 508", "content": "National  Center  for Emergin  g and  Zoonotic  Infectious  Diseases \nJYNNEOS Vaccine Safety Monitoring During the 2022 \nMpox Outbreak ─ United States \nJonathan Duffy, MD, MPH \nImmunization Safety Office Centers for Disease Control and Prevention \nAdvisory Committee on Immunization Practices \nFebruary 22, 2023 \n    \n     \n   \n    \n      CDC Mpox vaccine safety data sources \n Vaccine Adverse Event Reporting System (VAERS) \n Vaccine Safety Datalink (VSD) \n V-safe after vaccination health checker \n Single-patient emergency Investigational New Drug (EIND) procedures \n\nVAERS \n         VAERS is the nation’s early warning system for vaccine \nsafety \n\n       \n     \n          \n      \n         \n \n        \n        \n      \n               \n           \n               \n  JYNNEOS EUA* required reporting to VAERS for \nadverse events and vaccine administration errors \n The vaccination provider is responsible for MANDATORY reporting of the \nfollowing listed events following JYNNEOS to VAERS: \n– Vaccine administration errors whether or not associated with an adverse event \n– Serious adverse events (irrespective of attribution to vaccination) \n– Cases of cardiac events including myocarditis and pericarditis \n– Cases of thromboembolic events and neurovascular events \n*EUA indications: intradermal injection for individuals aged ≥18 and subcutaneous injection for individuals aged <18 years; Fact Sheet \nfor Healthcare Providers Administering Vaccine: Emergency Use Authorization of Jynneos (Smallpox and Monkeypox \nVaccine, Live, Non-Replicating) for Prevention of Monkeypox Disease in Individuals Determined to be at High Risk for Monkeypox Infection (fda.gov) \n\n   \n        \n           \n           \n          \n    \n  \n  \n  VAERS: JYNNEOS surveillance methods \n VAERS reports received and processed by January 20, 2023 \n Adverse event reporting rates were calculated by dividing the number of \nVAERS reports by the number of vaccine doses administered in the U.S. \n– Vaccine doses administered during May 22–January 13 and reported to CDC by January 23, 2023 \n• Dose 1: 698,188 \n• Dose 2: 426,980 \n• Total: 1,125,168 \n\n    \n \n \n \n  \n \n \n \n  \n   \n \n  \n  \n \n \n  \n  \n \n \n \n  VAERS: JYNNEOS report characteristics, n = 1,817 \nCharacteristic n (%) \nSex \nMale 1,415 (78) \nFemale 238 (13) \nNot reported 164 (9) \nAge \n0-17 25 (1) \n18-64 1,501 (83) \n≥65 83 (5) \nNot reported 208 (11) \nOther vaccines on same day \nYes 45 (2) \nNo 1,772 (98) Characteristic n (%) \nDose in series \n1 1,013 (56) \n2 471 (26) \nNot reported 333 (18) \nRoute of administration \nIntradermal 1,001 (55) \nSubcutaneous 378 (21) \nIntramuscular 211 (12) \nNot reported 227 (12) \n\n    \n      \n         \n  \n    \n    \n      \n       \n     VAERS: vaccine administration error reports \n Represent 50% of all JYNNEOS VAERS reports \n– Of these, 96% did not report an adverse health event \n Error reporting rate \n– Intradermal: 937 per million doses administered \n– Subcutaneous: 306 per million doses administered \n Errors frequently reported with attempted intradermal administration: \n– Absence of a wheal without vaccine leakage (42%) \n– Vaccine leakage from injection site (12%) \n\nrate \n  \n All adverse health events VAERS: adverse health event reporting rates per \nmillion doses administered by route of administration \n       \n      \n   \n  \n    \n Intradermal rate \nAll adverse health events 685 \nInjection site erythema 152 Dizziness 129 \nInjection site swelling 112 \nUrticaria 110 \nInjection site pruritus 93 \nErythema 78 \nSyncope 73 \nPruritus 72 \nHyperhidrosis 70 \nLoss of consciousness 69 Injec  tion sit  e erythema \n  Injection site swelling \n  Injection site pain Pain 107 \n107 \n99 96 \nFatigue Erythema Headache 80 77 77 \nDizziness 74 \n  Injection site pruritus Pyrexia 66 66 Subcutaneous \n639 \n  \n   \n      \n           \n    \n   \n          \n          \n        Serious Adverse Event definition \n Death \n A life-threatening adverse event \n Inpatient hospitalization or prolongation of existing hospitalization \n A persistent or significant incapacity or substantial disruption of the ability \nto conduct normal life functions \n A congenital anomaly/birth defect \n An important medical event that based on appropriate medical judgement \nmay jeopardize the individual and may require medical or surgical \nintervention to prevent one of the outcomes listed above \n\n      \n  \n  \n \n   \n  \n  \n \n \n        \n                \n     VAERS: serious adverse events reported after JYNNEOS*, \nn = 26 \nSAE reporting rate: 22 reports per million doses administered \n \n  \n \n  \n  \n  \n  \n  \n  \n   Dehydration Myocarditis  (n =5) \nDeath  (n=2)** Idiopathic thrombocytopenic \npur\npura Pericarditi  s (n=2) \nIn\njection site discoloration Urticari  a (n=2) \nIn\njection site pain Appendicitis \nInjection site scar Asepti  c meningitis \nMet\nhemoglobinemia Asthenia \nRetrograde amnesia Atrial  fibrillation \nRha\nbdomyolysis Cellulitis \nSudden hearing loss Chest  pain \n*The report of an adverse event to VAERS is not documentation that a vaccine caused the event. \n**Reported causes of death: drowning, cocaine toxicity. \nMyocarditis and pericarditis \n  \n        \n        \n          \n        \n  \n    \n          \n   Myocarditis and pericarditis \n Myocarditis and pericarditis have occurred following either primary \nvaccination or revaccination with live vaccinia virus smallpox vaccines \n– The mechanism is poorly understood, and it was unknown whether persons who receive JYNNEOS might experience myocarditis or pericarditis \n Epidemiologic analysis groupings: \n– Myocarditis with or without pericarditis \n– Pericarditis \n Surveillance risk interval: symptom onset within 30 days after vaccination \nCase definitions available at: DOI: 10.15585/mmwr.mm7027e2 \n\n      \n  \n       \n   \n     \n        \n              \n    \n \n  \n    \n        \n   Myocarditis rate per million persons during 30-day period \nObserved after JYNNEOS \nData source Dose 1 \ncases doses rate per million \n(95% CI) Dose 2 \ncases doses rate per million \n(95% CI) \nVAERS 2 726,851 2.75 (0.33–9.94) 3 445,019 6.74 (1.39–19.70) \nVaccine Safety \nDatalink 1 37,646 27 (0.67–148) 1 21,919 46 (1.15–254) \nExpected \n Historical myocarditis population background rates per million persons: \n– U.S. military in 20021: 21.6 \n– MarketScan database, males 18–64 yrs in 2017–20192: 2.7 – 7.5 \n Historical myocarditis rates after live, replicating smallpox vaccines (Dryvax or ACAM2000) ranged from 78 to 5,230 cases per million persons\n1,3 \nReferences: \n1) Halsell, et all. DOI: 10.1001/jama.289.24.3283; 2) Oster, et al. DOI: 10.1001/jama.2021.24110 ; \n3) Mandra, et al. DOI: 10.1017/dmp.2020.478 \n\n      \n  \n      \n \n     \n        \n                \n    \n \n  \n  \n          \n   Pericarditis rate per million persons during 30-day period \nObserved after JYNNEOS \nData source Dose 1 \ncases doses rate per million \n(95% CI) Dose 2 \ncases doses rate per million \n(95% CI) \nVAERS 4 726,851 5.50 (1.50–14) 2 445,019 4.49 (0.54–16.23) \nVaccine Safety \nDatalink 0 37,646 0 0 21,919 0 \nExpected \n Historical pericarditis population background rates per million persons: \n– Italy, 2001–20051: 22.8 \n– U.S. Nationwide Inpatient Sample database, 2003–20122: 4.7 \n Historical pericarditis rate after live, replicating smallpox vaccines (Dryvax \nor ACAM2000) was 925 cases per million persons in one U.S. military study3 \nReferences: \n1) Imazio, et al. DOI: 10.1136/hrt.2006.104067; 2) Kumar, et al. DOI: 10.1159/000445206 ; \n3) Engler, et al. DOI:10.1371/journal.pone.0118283 \n\nV-safe \n     \n         \n      \n   \n            \n  \n        \n          \n      \n          \n   V-safe Mpox: active vaccine safety monitoring \n Smartphone-based system that uses text messaging to initiate web-based \nsurvey monitoring for adverse events following vaccination \n V-safe is used to: \n– Characterize the basic safety profile of a vaccine when given outside a clinical trial setting \n– Provide information for public health communication around vaccine safety \n– Facilitate reporting to the Vaccine Adverse Event Reporting System (VAERS) \nfor medically attended adverse events following vaccination \n V-safe supplements CDC’s other vaccine safety monitoring systems, VAERS and \nVaccine Safety Datalink (VSD) \n\n     \n               \n  \n \n                     \n \n \n \n \n  \n   \n         \n      \n       \n        \nV-safe Mpox: characteristics of active participants* \nCharacteristic N=181 \nn (%) \nAge in years \n18-49 112 (61.9) \n50-64 56 (30.9) \n≥65 13 (7.2) \nGender identity \nMale 139 (76.8) \nFemale 28 (15.5) \nTransgender 7 (3.9) \nNone of the above or \nunknown 7 (3.9) \nImmunocompromised** 32 (17.1) Characteristic N=181 \nn (%) \nRace/Ethnicity \nWhite, non-Hispanic 111 (61.3) \nHispanic 28 (15.5) \nAsian, non-Hispanic 11 (6.1) \nBlack, non-Hispanic 10 (5.5) \nMultiracial, non-Hispanic 10 (5.5) \nOther race, non-Hispanic 2 (1.1) \nUnknown race or ethnicity 9 (5.0) \n*active participants defined as having completed at least one \nsurvey, November 16, 2022 – January 29, 2023 **defined as self-report of immunocompromising condition or taking immunosuppressive medications at the time of vaccination \n\n        \n        \n          \n        \n  \n                    \n          V-safe Mpox: reactions and health impact events reported by v-safe\nparticipants at least once in days 0-7 after vaccination, by dose\n100 \n90 \n81 \n62 \n26 \n19 \n14 \n5 80 \n54 \n16 14 \n10 \n0 \n0 10 20 30 40 50 60 70 80 Percentage \nAny injection site reaction Any systemic reaction Any health impact Unable to perform normal Unable to work or attend Sought medical care (clinic \ndaily activities school only) \nDose 1 Dose 2 \nIncludes 42 participants who completed at least one survey after dose 1 and 50 participants who completed at least one survey \nafter dose 2, data collected November 16, 2022 – January 29, 2023 \n\n          \n        \n            \n  \n                    \n          V-safe Mpox: top injection site and systemic reactions reported by v-safe\nparticipants at least once in days 0-7 after Mpox vaccination, by dose\n100 \n90 \n80 70 \n6462 \n60 50 \n40 \n30 20 10 \n0 \nRedness at site Itching at site Lump at site Swelling at site Fatigue Headache Pain at site Myalgia Rash at site Fever 55 52 50 \n40 \n24 24 24 \n17 17 54 \n46 \n40 42 \n28 26 \n22 \n16 \n6 \nDose 1 Dose 2 \nIncludes 42 participants who completed at least one survey after dose 1 and 50 participants who completed at least one survey \nafter dose 2, data collected November 16, 2022 – January 29, 2023 Percentage \n\nAdverse  Events  in  persons  <18 years  of age \n \n   \n \n  \n    \n    \n      \n     \n     Single-patient emergency  Investigational  New  Drug  \n(EIND) procedures \n\n\n CDC facilitate  d JYNNEOS EIND  authorization  s fro  m FDA  fo r 65 person  s aged  <1 8 \nyear  s prior  to  the  EUA  being  issue  d o  n August  9,  2022 \n– CDC  solicite  d informatio  n fro  m vaccine  provider  s about  adverse  event  s \noccurring  durin  g the  28 day  s afte  r each  dose \n Ages: 4 months to 17 years \n Sex: 58% male \n Adverse events reported: \n– D\nose 1: 10 (18%) of 57 \n– Dose 2: 5 (21%) of 24 \n– Injection site reactions: pain, erythema, swelling, and induration \n– Systemic adverse events: fever, fatigue, and headache \n No serious adverse events were reported \n\n      \n            \n    \n        \n     \n      \n      \n       \n    VAERS: reports for persons aged <18 years \n JYNNEOS vaccine was administered to 1,245 persons aged <18 years in the \nU.S during this surveillance period \n VAERS received 25 reports for persons aged <18 years \n– Ages from 12 through 17 years \n– Vaccine administration errors, n = 21 (84%) \n• e.g., administered intradermal dose instead of subcutaneous dose \n– Only 1 adverse health event reported: syncope \n– No serious adverse events reported \n\nConclusions \n       \n         \n        \n           \n     \n             \n          \n   Conclusions \n JYNNEOS post-licensure and post-authorization vaccine safety surveillance \nfindings to date are consistent with those observed in clinical trials \n No new or unexpected safety concerns have been identified \n Serious adverse events were rare among adults, and none have been identified among persons aged <18 years \n VAERS and Vaccine Safety Datalink data do not suggest an increased risk for myocarditis or pericarditis following JYNNEOS, but the possibility of a small risk cannot be excluded \n\n    \n \n      \n                  \n         For more information, contact CDC \n1-800-CDC-INFO (232-4636) TTY: 1-888-232-6348 www.cdc.gov \nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.", "summary": "National  Center  for Emergin  g and  Zoonotic  Infectious  Diseases  JYNNEOS Vaccine Safety Monitoring During the 2022  Mpox Outbreak ─ United States  Jonathan Duffy, MD, MPH  Immunization Safety Office Centers for Disease Control and Prevention  Advisory Committee on Immunization Practices  February 22, 2023                            CDC Mpox vaccine safety data sources   Vaccine Adverse Event Reporting System (VAERS)   Vaccine Safety Datalink (VSD)   V-safe after vaccination health…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/Mpox-03-Duffy-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 26}
{"title": "Mpox 04 Chard 508", "content": "National  Center  for Emerging  and Zoonotic  Infectious  Diseases \nJYNNEOS Vaccine Effectiveness \nAnna Chard, PhD, MPH \nLT, US Public Health Service \nVaccine Effectiveness Team \nVaccine Task Force \n2022 Multinational Mpox Outbreak Response \nCenters for Disease Control and Prevention \nAdvisory Committee on Immunization Practices \nFebruary 22, 2023 \n        \n         \n        \n      \n \n        \n           \n         \n         \n         Background \n Efficacy of JYNNEOS against mpox has been inferred from animal and \nimmunogenicity studies, but has never been demonstrated in clinical trials \n Noreal-world vaccine effectiveness (VE) estimates for JYNNEOS against \nmpox disease prior to current multinational outbreak \n Key questions: \n1. What is the effectiveness of JYNNEOS vaccine against mpox disease? \na) What is VE of partial (1 dose) versus full (2 doses) vaccination? \n2. Are there differences in VE by route of vaccine administration? \n3. Are there differences in VE among persons with immunocompromising conditions? \n4. What is the duration of protection conferred from JYNNEOS vaccine? \n   \n \n          \n     \n         \n   \n      \n             \n \n              \n           \n    \n              \n  Organization of presentation \n Vaccine performance \n Incidence of mpox among unvaccinated persons versus persons receiving ≥1 JYNNEOS \ndose in the United States (U.S) \n Vaccine effectiveness (VE) of JYNNEOS given as post-exposure prophylaxis \n(PEP) against mpox disease, New York City \n VE of JYNNEOS given as pre-exposure prophylaxis (PrEP) against mpox \ndisease \n1. Israel single dose VE Study : Real-world effectiveness of a single dose of mpox vaccine \nin males \n2. EPIC Cosmos Case-Control Study: VE of 1 and 2 doses against mpox disease in the U.S \n3. Multi-jurisdictional Case-Control Study : Interim estimate of VE of 2 doses against \nmpox disease in 12 U.S. jurisdictions \n4. New York State Case-Control Study : Preliminary estimates of VE of 1 and 2 doses \nagainst mpox disease \nVaccine  performance \n     \n          \n  \n        \n           \n         \n  \n    \n \n             \n     \n       \n                       \n \n                       \n            Weekly mpox incidence by vaccination status: Methods \n Data sources: Mpox case data, vaccine administration data, estimates of the \nvaccine eligible population* \n Design: Comparison of mpox incidence among persons who were \nunvaccinated and those who had received either 1 or 2 JYNNEOS doses \n Population: 9,544 reported mpox cases among men aged 18–49 years from \n43 U.S. jurisdictions \n Time period: July 31–October 1, 2022 \n Analysis: \n Estimated weekly mpox incidence for persons with partial (1 dose) and full (2 doses) \nvaccination and persons eligible but unvaccinated \n Calculated incidence rate ratio using negative binomial regression \n*Estimated population per jurisdiction of men who have sex with men (MSM) who are living with HIV or MSM who are eligible for HIV pre -\nexposure prophylaxis. \nSource: Payne AB, et al. Reduced Risk for Mpox After Receipt of 1 or 2 Doses of JYNNEOS Vaccine Compared with Risk Among Unvaccinated \nPersons — 43 U.S. Jurisdictions, July 31–October 1, 2022. MMWR Morb Mortal Wkly Rep 2022;71:1560–1564. \n        \n              July 31, 2022 – October 1, 2022 (43 U.S. jurisdictions**) \nUnvaccinated \n350 \n300 \n250 \n200 150 \n100 \n50 \n0 Vaccine dose 1 received ≥ 14 days earlier \nVaccine dose 2 received ≥ 14 days earlier Monkeypox Incidence \n31-Jul-22 \n2-Aug-22 4-Aug-22 6-Aug-22 8-Aug-22 \n10-Aug-22 12-Aug-22 14-Aug-22 16-Aug-22 18-Aug-22 20-Aug-22 22-Aug-22 24-Aug-22 \n26-Aug-22 \n28-Aug-22 30-Aug-22 \n1-Sep-22 3-Sep-22 5-Sep-22 7-Sep-22 9-Sep-22 \n11-Sep-22 13-Sep-22 \n15-Sep-22 \n17-Sep-22 19-Sep-22 21-Sep-22 23-Sep-22 25-Sep-22 \nWeek       \n  Weekly mpox incidence,*by vaccination status \neligible for vaccination§among males aged 18–49 years \n                                        \n                                           \n         \n                       \n                                \n                        \n                                               \n              \n                                     \n        \n        \n  \n   \n       \n        \n  \n     \n    \n Mpox incidence among unvaccinated \nindividuals was 7.4 (95% CI = 6.0–9.1) times \nas high as persons receiving 1 dose of \nJYNNEOS vaccine . \nMpox incidence among unvaccinated \nindividuals was 9.6 (95% CI = 6.9–13.2) \ntimes as high as persons receiving 2 doses \nof JYNNEOS vaccine . \nNo difference observed in vaccine \nperformance be tween subcutaneous and \nintradermal administration . \n* Cases per 100,000 population. Rate in vaccinated persons = number of probable or confirmed cases reported to CDC with date of illness onset, specimen collection, lab test completion, admission, diagnosis, discharge, case investigation start date, or date first electronically submitted or \nreported to the county, state, or public health department (earliest available date) ≥14 days after receiving the first dose or second dose of JYNNEOS vaccine among total vaccinated population as of 2 weeks previously. Rate in unvaccinated persons = number of probable or confirmed cases \nreported to CDC without evidence of vaccination among total unvaccinated population. § Gay, bisexual, and other men who have sex with men who have HIV infection or who are eligible to receive HIV preexposure prophylaxis were considered eligible for vaccination. ¶ Alabama, Alaska, California, Colorado, Connecticut, District of Columbia, Florida, Georgia, Hawaii, Idaho, Illinois, Iowa, Kansas, Kentucky, Louisiana, Maine, Maryland, Massachusetts, Michigan, Minnesota, Mississippi, Missouri, Montana, Nevada, New Hampshire, New Mexico, New York (excluding New York City), North Dakota, Ohio, Oklahoma, Oregon, Pennsylvania, Puerto Rico, Rhode Island, South Carolina, South Dakota, Tennessee, Utah, Vermont, Virginia, West Virginia, Wisconsin, and Wyoming. ** Jurisdictions were included if age and sex assigned at birth or gender identity was available for ≥70% of cases reported, vaccination status was available for ≥50% of cases in males (defined by either sex assigned at birth or gender identity) aged 18–49 years or the jurisdiction confirmed cases were linked to immunization registry entries, and de-identified vaccination administration data were submitted to CDC. \nSource : Payne AB, et al. Reduced Risk for Mpox After Receipt of 1 or 2 Doses of JYNNEOS Vaccine Compared with Risk Among Unvaccinated Persons — 43 U.S. Jurisdictions, July 31–October 1, 2022. MMWR Morb Mortal Wkly Rep 2022;71:1560–1564. \n    \n    \nVaccine effectiveness  of JYNNEOS \nadministered  as PEP against  mpox \n         \n \n             \n            \n           \n                 \n \n          \n    \n              \n        \n           \n              \n   \n           \n            JYNNEOS effectiveness as PEP against mpox, New York City \n(unpublished data) \n Design: Cohort evaluation of individuals ages >18 years residing in NYC identified through \nroutine Department of Health contact investigations to a case-patient with mpox between May \n22—August 24, 2022 and no vaccination or disease history prior to exposure \n PEP: Receipt of 1st dose of JYNNEOS <14 days of exposure and prior to date of symptom onset, \nif applicable \n Case-patient : Exposed individuals who developed symptom onset <21 days after exposure \n(incubation period) with laboratory confirmation \n Analysis : VE of a single dose of JYNNEOS administered subcutaneously <14 days after exposure \nas PEP for preventing laboratory-confirmed mpox disease as [(1 – Relative Risk) × 100%] \n Results: Among individuals with high-risk* exposure, vaccine effectiveness was 77% (95% CI: \n51%-92%) with PEP <14 days after last exposure (n=273) and 79% (46%-94%) with PEP <14 \ndays after first exposure (n=208)** \n*Defined according to the CDC Interim Community Exposure Risk Assessment and Recommendations \n***Unadjusted; in univariate analyses, race/ethnicity and age-group were not significantly associated with mpox disease \n    \n   \nVaccine effectiveness of JYNNEOS \nadministered as PrEP against mpox \n    \n        \n \n  \n     \n                             \n                \n                   Israel single-dose VE study: Methods \n\n\n V accination: Single, subcutaneous dose of Modified Vaccinia Ankara-Bavarian \nNordic (MVA-BN) \n Design:  Retrospective,  observational cohort  using electronic  health  record  s \nfrom  a singl  e integrated  health  center  in  Israel \n Population:  2,054  men  eligible*  for  vaccinati  on \n Time  period:  July 31 , 2022  – December 25 , 2022 \n Analysis  : \n VE estimated  using  Co x proportional  hazards  regressio  n with  vaccination  status  as  a  \ntime-varyi  ng covariate \n M\nodel adjusted for sociodemographic and clinical risk factors \n*Males aged 18 – 42 years who were dispensed HIV-PrEP at least for one month since January 1, 2022, or (b) males aged 18 – 42 years who were diagnosed with HIV \nand also were diagnosed with one or more sexually transmitted infections (STIs) since January 1, 2022. \nSource : Sagy, Y. W. et al. Real-world effectiveness of a single dose of mpox vaccine in males. Nature Medicine https://doi.org/10.1038/s41591-023-02229-3 (2023). \n    \n   \n  \n \n   \n     \n                  \n Israel single-dose VE study: Results \n• 5 mpox cases among vaccinated \nindividuals \n• 16 mpox cases among \nunvaccinated individuals \n• Adjusted single-dose vaccine \neffectiveness was 86% (95% CI: 59%-95%) \nSource : Sagy, Y . W. et al. Real-world effectiveness of a single dose of mpox vaccine in males. Nature Medicine https://doi.org/10.1038/s41591 -\n023-02229-3 (2023). \n    \n          \n        \n          \n     Epic Cosmos Case-Control Study: Methods \n Data Source: Epic’s electronic health record (EHR) platform, Cosmos, which \nincludes records from >169 million patients across the U.S. \n\n \n \n\n \n \n  Analysis: \n Design: Case-control analysis, matched 1:4 based on week of index event, \nHHS region, and gender identity \nCase patients:  Patients  wit  h an mpox diagnosis  or positive  orthopoxvirus or  mpox \nvirus  laboratory  result  from  8/15  - 11/19/2022 \nControl  patients : Patients  wit   h an incident  HIV diagnosis  or  HIV pre-exposur  e \nprophylaxis  (PrEP) prescription  from  8/15  - 11/19/2022 \nVE estimated  using  conditional  logistic  regression \nAdjusted  for age , race/ethnicity,  social  vulnerability  index  , immunocompromisin  g \nconditions \nStratified  by route   of administration  and immunocompromised  status \n   \n       \n    \n     \n     \n     \n       \n    \n     \n     \n  Cases Controls Adjusted* VE (95% CI) (n=2,913) (n=8,319) \nOverall VE, full vaccination (2 doses) 25 335 66 (47, 78) \nNo immunocompromising conditions 14 312 76 (58, 87) \n2 doses administered subcutaneously 6 63 54 (-9, 81) 2 doses administered intradermally 5 42 46 (-45, 80) 2 doses administered heterologously 8 150 75 (48, 88) \nOverall VE, partial vaccination (1 dose) 146 1000 36 (22, 47) \nNo immunocompromising conditions 102 932 41 (25, 53) 1 dose administered subcutaneously 106 704 32 (15, 45) 1 dose administered intradermally 27 186 41 (7, 62) \n-60 - 40 - 20 0 20 40 60 Vaccine Effectiveness (% )80 100 \n         \n                  \n       \n Epic Cosmos Case-Control Study: JYNNEOS VE for fulland partial \nvaccination, August 15-November 19, 2022, United States \n(unpublished data) \n*Adjusted for age, race/ethnicity, social vulnerability index, and immunocompromising conditions .\nC\nases/controls matched on week of index event, HHS region, gender identity .\n   \n  \n           \n        \n        \n    \n        \n \n      \n         \n          \n        Multi-jurisdictional Case-Control Study: Methods \n Design: Case-control study \n Population: Men who have sex with men; ages 18-49; 12 U.S. jurisdictions \n Methods: \n Cases identified from jurisdictions’ probable and confirmed mpox case \nlists \n Controls identified from healthcare settings providing HIV PrEP or \nsexually transmitted infection (STI) clinics \n Demographics, exposure history, and vaccination history collected using \nelectronic surveys \n Vaccination status confirmed by state immunization registries \n Analysis: Logistic regression with random intercept for jurisdiction and \nadjusted for age, race/ethnicity, number of sexual partners, close contact with a confirmed/probable case, and month of index event \n   \n      \n   \n \n     \n  \n \n          \n  \n     \nMulti-jurisdictional Case-Control Study Interim Results: VE for full \nvaccination (unpublished data) \nCases Controls Adjusted* VE (95% CI) (n=167) (n=256) \nOverall VE, full vaccination (2 doses) 14 122 76% (48%-89%) \nNo immunocompromising conditions 8 61 90% (66%-97%) \nImmunocompromising conditions \nOverall VE, partial vaccination (1 dose) Not sufficiently powered for interim analysis \nNo immunocompromising conditions \nImmunocompromising conditions \n0 20 40 60 80 100 \nVaccine Effectiveness (%) \n*Adjusted  for age, race/ethnicity,  immunocompromised  status,  reported  clos  e contact  with  a \nconfirmed/suspected  mpox cas  e in   3 week  s prior  to  index  event,  and month  o f index  event\n       \n \n           \n    \n       \n           \n   \n         \n   \n    \n   \nNew York State Case-Control Study: Preliminary Estimates \n(unpublished data) \n Data source: Linkage of case surveillance to immunization registry in New York \nState, excluding New York City \n Cases : Adult male mpox cases during July 24 – October 31, 2022 \n Controls : Adult male STI cases (rectal gonorrhea or primary syphilis) during July \n24 – October 31, 2022 \n Analysis: Conditional logistic regression model adjusted for diagnosis week, race, \nage, region within state \nmpox cases \n(n=252) STI controls \n(n=255) VE (95% CI) \nPartial vaccination 10 (4%) 23 (9%) 68% (25%, 86%) Unvaccinated 230 (91%) 204 (80%) ref. \nFull vaccination 2 (1%) 19 (7%) 89%  (44%, 98%) \nSummary \n      \n       \nCases Controls    Adjusted* VE (95%\nEpic   Cosmos  case-control study 25 335  66% (47%- 78%) \n New   York State  case-control study 2 19  89% (44%-98%) \n Partial  vaccination  (1 dose) \n5 16  86% (59%-95%) \nEpic   Cosmos  case-control study 146 1000  36% (22%-47%) \n  Vaccine effectiveness of JYNNEOS against mpox ranges from 66% -\n89% for full vaccination and 36%-86% for partial vaccination \nCI) \n0 20 40 60 80 100 \nVaccine Effectiveness (%)  Full  v accination  (2 doses) \n Mul\nti-jurisdictional  case-control study 14 122  76% (48%-89%) \n  Israel single-dose study \n New   York State  case-control study 10 23  68% (25%-86%) \n     \n \n      Vaccine effectiveness of JYNNEOS against mpox \n\n\n\n\n JYNNEOS  vaccine i s effective at  reducing  risk  of mpox disease \n Protection  provided  by both  1  and 2 doses  of JYNNEOS  vaccine \n Highest  protection  provided  by 2 doses  , regardles  s of route of  \nadministration \n Further  research  needed  to evaluate  whether  immunocompromised  statu  s \nmodulates  V E \n Further research needed to assess duration of protection \n  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n  \n \n \n \n \n \n \n    \n \n \n \n  \n \n \n  \n  \n      \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n   \n \n \n  \n \n \n \n \n \n \n \n \n  \n \n  \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n   \n \n  \n \n \n \n \n \n \n \n \n \n  \n \n \n  \n \n \n \n    \n     \n \n \n  \n \n \n \n \n \n \n \n \n \n \n \n Acknowledgements \n• Alpha Oumar Diallo • Jennifer B. Rosen • Jemma Rowlands • Gennesis Quinonez \n• Robert J. Arciuolo • Ghinwa Dumyati • Paola Santos • Alexandra Dalton \n• Preeti Pathela • Christina Felsen • AmberJean Hansen \n• Amy Fothergill • Jennifer Baumgartner • Erin Licherdell • James Meek \n• Julia Latash • Kristin Smith • Linda Niccolai • Leora Feldstein \n• Lenka Malec • Shealynn Hilliard • Quyen PhanLynn Sosa • Nicholas Deputy • Ellen H. Lee • Will Still • Sydney Jones \n• Danielle Moulia • Vasudha Reddy • Allison Morrow • Gabriela Betancourt \n• Renee King • Sarah Gillani • Ciarra Leocadio • Amanda Payne • Joseph Edward Real • Eric Anthony • Preeti Pathela \n• Tom Shimabukuro • Jane R. Zucker • Mary Fran DeRose • Robyn Weber \n• Jessica Castilho • Gregory Prahl • Mo Patel • Investigators from New York State Health • Mary Margaret Fill • Masayo Nishiyama \n• Adam Cohen Dept • Keipp Talbot • Jesse J. Carlson \n• Eli Rosenberg • Tiffanie Markus • Kevin Kamis • Rosalind Carter \n• Vajeera Dorabawila • Danielle Ndi • Gena Simien • Amanda Cohn • Rachel Hart-Malloy • Kristine Mansilla-Dubon • Karen A. Wendel \n• Daniel Payne • Wilson Miranda • Bentley Akok • Ginger Stringer \n• Bridget Anderson • Sweta Tiwari • Rachel Herlihy • Logan Ray • Bryon Backenson • Caleb Wiedeman • Jennifer House \n• Kristen Kugeler • Charlotte DelBarba • Jacqueline Logan • California Department of Public Health \n• Meaghan Abrego • Greg Chambers • Alameda County Public Health • Michelle Canning Department (CA) • Yelena Tourkina • Cori Tice • Robbie Snyder • Matthew Cole • Kim Toevs • Claire McGarry • Shua Chai • Kennedy Houck • Emily Lutterloh • Lynn Rampe • Arthur L. Reingold • Eric Richardson • Michele Boulais • Steven Gibson • Nathaniel Lewis • Jaxon Mitchell • Ethan Mitchell • Eileen Dunne • Josh Arevalo • Jennifer Farrar • Charles Gonzalez • Rebecca Fisher • Melissa Sutton • Travis O’Donnell • Lizzie White • Phoebe Danza • Paul Cieslak • Michael Kharfen • Erin Peterson • Epic COSMOS Investigators • James McDonald • Sam Hawkins • Jane Lam • Jackie Gerhart • Ursula Bauer • Amber Britton \n• Gabriel Garcia-Lopez • Danessa Sandman • Bianca Perez • Robert Bolan • Dave Little • Multi-jurisdictional case-control study • Erica Hazra • Sharon Balter • Cory Sweet investigators: • Molly McAlvany • Sonali Kulkarni • Joe Deckert • Taelor Moran • Bridget Anderson • Nava Yeganeh • Eric Barkley • Tamsin van der Woude • Suzanne McGuire • Andrea Kim • Neil Sandburg • Katherine Lee • Adam Rowe \n• Rachael Gill • Kerianne Engesser • Investigators from NYC Health \n   \n1-800-CDC-INF  O (232-4636) \nTTY:   1-888-232-6348  \nwww.cdc.gov", "summary": "National  Center  for Emerging  and Zoonotic  Infectious  Diseases  JYNNEOS Vaccine Effectiveness  Anna Chard, PhD, MPH  LT, US Public Health Service  Vaccine Effectiveness Team  Vaccine Task Force  2022 Multinational Mpox Outbreak Response  Centers for Disease Control and Prevention  Advisory Committee on Immunization Practices  February 22, 2023                                                                                         Background   Efficacy of JYNNEOS against mpox has been…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/Mpox-04-Chard-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 21}
{"title": "Mpox 05 Delaney 508", "content": "x\nInformation on Mpox vaccine acceptability and uptake from cross-\nsectional surveys \nKevin P . Delaney, PhD, MPH \nCommunity Engagement and Vaccine Policy and Implementation Task Force 2022 Multinational Mpox Response Centers for Disease Control and Prevention \nAdvisory Committee on Immunization Practices \nFebruary 22, 2023 \nwww.cdc.gov/mpo \nInformation from US-based Clinicians \n Sermo – online community of >1.3 million clinicians \n Conducted a worldwide survey of physicians \nJuly 31-August 1st; results reported 8/8/2022 \n• At that point (N=415 US-based clinicians) \n• 69% said that the US did not have enough \nmpox vaccine to handle the outbreak \n Brief updated survey (N=62) on 9/12/2022 \n• 66% had treated at least one patient with monkeypox \n• 76% knew where to send patients for JYNNEOS vaccination \n• 86% wanted to be able to offer vaccine in their practice \nMore at https://app.sermo.com/barometer/unitedstates \n   \n     \n     \n     \n     \n         \n    \n     \n        \n        \n          \n  \n   Information from affected populations \n\nStudies included \nStudy Timeframe Population Methods \nPorter  Novelli August  – \nDecemb\ner 1 6 N= up to 371 LGBTQ+ \nData  weighted  to matc  h \ncensus  population Four  KAP surveys  in the general  populatio  n \nincludin  g LGBTQ+ \nAMETHST : Ame rica n \nTransformative  HIV  \nStudy Aug 9th – \nNovember  15th \nAMIS : America  n \nMen’s Internet  \nSurvey N = 824 GBMSM Emory  conducte  d a one-time  KAP survey  of\n2021  AMIS  population  . \nSurvey  available  \n  he\nre \nOctober  6 – \nD\necember  31 N=3041  GBMSM Ongoin  g recruitment  of the 2022  AMI  S \nsurvey  summarized  through  12/31 \n \nSan Francisco  study   \namon  g persons  \nexperiencin  g \nhomelessness  (PEH) N= 2 73 \n57 with  higher  risk sexua  l \nactivity \n35 GBMSM N=8,551 5\n0% Blac  k and  Latinx  \nGBMSM Mon t\nhly cross-sectional  surv ey to recruit  \nnew  cohorts  of persons  at risk for HIV . \nQuestions  related  to mpox added  in 2022 \nCross-sectional  s urvey  among  PEH to \nunderstand  vaccine  acceptabilit  y and\ncoverage  \n  A\nugust  5 – \nA\nugust  15 \nOct 2 3rd – \nNovember  5th \n \nAMETHST : Ame rican   \nTransformative  HI V \nStudy Aug 9th – \nNovember  15th N=8,551 \n50%  Blac  k and  Latinx  \nGBMSM Monthly  cross-sectional  survey  to recruit  \nnew  cohorts  of persons  at risk for HIV . \nQuestions  related  to mpox  added  in 2022 \nAMIS : America  n \nMen’s Internet  \nSurvey \nOctober  6 – \nDecember  31 N=3041  GBMSM Ongoin  g recruitment  of the 2022  AMI  S \nsurvey  summarized  through  12/31 \nSan Francisco  stud  y \namon  g persons  \nexperiencin  g \nhomelessness  (PEH) Oct 23rd – \nNovember  5th N= 273 \n57 with  higher  risk sexua  l \nactivity \n35 GBMSM Cross-sectional  survey  among  PEH t o \nunderstand  vaccine  acceptabilit  y an  d \ncoverage Studies included \nTimeframe Population Methods \n Porter Novelli August  – \nD\necember  16  N= up to 371 LGBTQ+ \nData  weighted  to match   \ncensus  population Four  KAP surveys  in the general  populatio  n \nincludin  g LGBTQ+ \nAugust  5 – \nAugust  15 N = 824 GBMSM Emory  conducte  d a one-time  KAP survey  of  \n2021  AMIS  population  . \nSurvey  available  here Study \n         \n        \n       \n           \n    \n       \n           \n     \n        Methods \n Porter Novelli conducted 4 online general population surveys during fall \n2022 on knowledge, attitudes, and beliefs of mpox-related topics \n Data are weighted to match U.S. Census proportions \n Survey includes a question about whether the individual “identifies as a \nmember of the LGBTQ+ community” \n Most responses remained stable across the 4 months \n In the December Survey we asked specific questions designed to more directly measure mpox vaccine acceptability and value \n All results here are stratified by LGBTQ+ status \n\n         \n \n      \n  \n    \n \n  \n \n    \n   \n   \n    \n        \n    \n  \n   \n   \n    \n               The population thinks that the vaccine is safe and \nimportant \nLGBTQ+ Status \nVariable Overall, N = \n1,3231 Part of LGBTQ+ \nCommunity, N \n= 1471 Not part of \nLGBTQ+ \ncommunity, N \n= 1,1761 \nThe monkeypox vaccine is safe \nAgree 36% (475) 51% (76) 34% (399) \nDisagree 9.7% (128) 11% (16) 9.5% (112) \nDon't Know \nIt is important for me to get the \nmonkeypox vaccine to protect myself against monkeypox 54% (721) 38% (56) 57% (665) \nAgree 33% (440) 50% (74) 31% (366) \nDisagree 30% (400) 18% (27) 32% (373) \nDon't Know 37% (484) 32% (46) 37% (437) \n1% (n)2Bolded numbers are significant p < .05, chi-squared test with Rao & Scott's second-order correction \n \n  \n      \n    \n        \n \n  \n   \n          \n        \n     \n  \n    \n           \n   \n  \n  \n        \n   \n   \n  \n \n  \n  \n     \n      \n    Studies included \nStudy Timeframe Population Methods \nPorter Novelli August – \nDecember 16 N= up to 371 LGBTQ+ \nData weighted to match \ncensus population Four KAP surveys in the general population \nincluding LGBTQ+ \nAMETHST :Ame rican \nTransformative HIV \nStudy Aug 9th – \nNovember 15th N=8,551 50% Black and Latinx \nGBMSM Monthly cross-sectional survey to recruit \nnew cohorts of persons at risk for HIV. \nQuestions related to mpox added in 2022 \nAMIS :American \nMen’s Internet \nSurvey August 5 – \nAugust 15 N = 824 GBMSM Emory conducted a one-time KAP survey of 2021 AMIS population. \nSurvey available here \nOctober 6 – \nDecember 31 N=3041 GBMSM Ongoing recruitment of the 2022 AMIS \nsurvey summarized through 12/31 \nSan Francisco study among persons \nexperiencing \nhomelessness (PEH) Oct 23\nrd – \nNovember 5th N= 273 57 with higher risk sexual \nactivity \n35 GBMSM Cross-sectional survey among PEH to understand vaccine acceptability and \ncoverage \n\n    \n          \n  \n       \n          \n   \n       \n      \n   \n      \n       \n \n    \nAMETHST: American Transformative HIV Study \n NIH funded study to build new cohorts of individuals at \nrisk for HIV \n FY1-FY2 (2022-2024): Build cohort, enrolling at least 5000 people at increased risk for HIV infection; at least 50% people of color \n• AMETHST cohort will focus on the mechanisms \nthrough which meth use increases bio-behavioral vulnerability to HIV. \n• Added questions re: Mpox knowledge, vaccine uptake and behavior change to their screening questionnaires \n• 8551 participants surveyed through 11/15/2022 \nhttps://grants.nih.gov/grants/guide/rfa-files/RFA-AI-21-018.html \n\n       \n       WORRY ABOUT MPOX OVER THE LAST 2 WEEKS \n34.0% 40.6% \n58.0% \n66.4% \n66% 59% \n42% \n34% \nAug Sept Oct Nov \nSome or more than half of the days Never   \n  \n  \n  \n While Mpox \nconcern has decreased over time, some concern remains \n\n       \n   \n  \n  \n    \n     \n   >85% of respondents remain interested in vaccination \n Vaccine coverage nearly November \nOctober \nSeptember \nAugust \n0% 20% 40% 60% 80% 100% doubled between August \nand September \n As o f  November,  30.5%  \nreceived  at least  one dose \n• ~90%  overall and  88%  of  \nthe sample  fro  m \nNovember  either  hav  e \nbeen  vaccinated  or  \nwould  like to be  \nvaccinated Vaccinated \nExtremely likely to get vaccinated Li\nkely to get vaccinated or unsure \nUnlikely to get vaccinated \n\n        \nNovember \nOctober Proportion that received at least one dose of vaccine \nSeptember \nAugust \n0 10 20 30 40 50 60 70 80 90 100 \nOther Latinx Black White       \n    \n   \n   \n   \n   \n  Vaccine uptake by Month and Race/Ethnicity, \nAMETHST recruitment survey August-November 2022 \n In August, Black \nparticipants had higher vaccine coverage than participants from other racial and ethnic groups \n\n      \n    \n   \n   \n   \n   \n          Vaccine uptake by Month and Race/Ethnicity, \nAMETHST recruitment survey August-November 2022 \n In August, Black \nparticipants had higher vaccine coverage than participants from other racial and ethnic groups \nNovember \nOctober Proportion that received at least one dose of vaccine \nSeptember \nAugust \n0 10 20 30 40 50 60 70 80 90 100 \nOther Latinx Black White \n\n        least one dose of vaccine \nNovember       \n    \n \n \n  \n   \n  Vaccine uptake by Month and Race/Ethnicity, \nAMETHST recruitment survey August-November 2022 \n In A ugust,  Blac  k \nparticipants  had higher \nvaccine coverage than \nparticipants from other \nracial and ethnic groups \nOctober \n But b lack  men  did no t \nsee the “doubling”   in \nvaccine  coverage  tha t \nwe reported  overall September \nAugust Proportion that received at \n0 10 20 30 40 50 60 70 80 90 100 \nOther Latinx Black White \n\n \n  \n \n   \n \n \n \n \n \n \n \n \n VVVVaaaacccccccciiiinnnneee    e uuuuppppttttaaaakkkkeee    e bbbbyyy  y   rrrraaaacccceeee,,,  ,   ggggeeeennnnddddeeeerrr  r   iiiiddddeeeennnnttttiiiittttyyy    y aaaannnnddd  d   \nsssseeeexxxxuuuuaaaalll  l   oooorrrriiiieeeennnnttttaaaattttiiiioooonnnn,,,  ,   AAAAuuuugggguuuusssstttt-- --NNNNoooovvvveeeemmmmbbbbeeeerrr  r   2222000022222222 \nHad at least  one dose  of the MPV  vaccine \nNo=5943 Yes=2608 Chi-sq p \nn n Row % \nRace or ethnicity 11.802 0.008 \nWhite 2907 1323 31.28% \nBlack 895 329 26.88% \nLatinx 1419 625 30.58% \nOther 659 331 33.43% \nAge (M, SD) 35.65, 10.44 37.12, 10.74 35.098 0.000 \nSex Identity 23.674 0.000 \nCisgender male 5204 2364 31.24% \nTransgender male 12 1 7.69% \nTransgender female 138 30 17.86% \nNon-binary, Other 589 213 26.56% \nSexual orientation 161.159 0.000 \nGay, Queer 4378 2245 33.90% \nBisexual 1093 241 18.07% \nSomething else 472 122 20.54% \nStudies included \nStudy Timeframe Population Methods \nPorter  Novelli August  – \nDecember  16  N= up to 371 LGBTQ+ \nData  weighted  to matc  h Four  KAP surveys  in the general population   \nincluding LGBTQ+  \ncensus  population \nAMETHST :Ame rican  Aug 9th  – \nTransformative  HIV  15th November  \nStudy \nAMIS :American   N = 82 4 GBMSM  Emory  conducted  a one-time  KAP survey  of  \nMen’s Internet  2021 AMIS population.    \nSurvey Survey  available  here \nOctober  6 – \nDe\ncember  31 N=3041  GBMSM  \nN=8,551 \n50% Black   and Latinx   \nGBMSM Monthly  cross-sectional  survey to   recruit  \nnew  cohorts  of persons  at risk for  HIV.  \nQuestions  related to   mpox added in   2022 \nAugust 5   – \nAugust 15  \nOngoin  g recruitment  o f the 2022  AMI  S \nsurvey  summarized  through  12/31 \n San  Fra\nncisco  study \n among p e\nrsons  \n experi\nencing \n homelessness (PEH) Oct 23rd  – \n5th  November N= 273 \n 5\n7   wi th higher  risk sexual\nactivity \n 35 GBMSM  Cros s-sectional  survey    among PEH to \n unde rstand  vaccine  acceptability  and \ncoverage \n    \n          \n         \n     \n      \n          \n  \n          \n  \n    \n      \n           American Men’s Internet Survey (AMIS) \n In August 2022, Emory University conducted a special one-time survey with \n2021 AMIS participants to explore knowledge, attitudes and practices related to the US monkeypox outbreak. \n• Also asked about behavior change and vaccination \n• Survey conducted August 5-15, during the peak of the current outbreak \n Survey is available here . \n Questions ask about vaccine knowledge, access or availability, and trusted \nsources of advice \n 824 men completed all questionnaire sections \n• Overall, 53.1% reported concern about getting mpox \n• 18.6% of the sample had received at least one dose of mpox vaccine \nhttps://www.cdc.gov/mmwr/volumes/71/wr/mm7135e1.htm \n\n   \n   \n     \n      \n       \n       \n        \n        \n     \n        \n          AMIS survey results\nConducted August 5-15th2022\n•18.2% of the sample had\nreceived at least one dose ofMPOX vaccine“Equitable vaccine program implementation involve…, engaging \ndiverse partners already working with special populations, \ndelivering vaccines through mobile outreach and pop-up events, and diversifying times and locations for vaccine administration ” \n“Expanding vaccine availability geographically, including diversifying vaccination locations to include nonurban areas, can help ensure that those who need vaccination have access to it .” \nhttps://www.cdc.gov/mmwr/volumes/71/wr/mm7135e1.htm \n\nhttps://www.whitehouse.gov/briefing-room/statements-releases/2022/08/30/fact-sheet-white-house-monkeypox-response-team-announces-new-plans-to-support-large-lgbtqi-events-and -\nequity-interventions-to-reach-communities-at-highest-risk-of-contracting-the-virus/ \n\n   \n \n    \n  \n  \n   \n \n \n   \n   \n Vaccine Equity Pilot Program \nCreated to: \n• Support innovative ways to \n 15 address vaccination disparities Jurisdictions \n• Encourage vaccination \ncoordination between health departments and community -\nbased organizations 28  \nPrograms • Promote innovation to strengthen existing vaccination \ninfrastructure \n~25k Doses \n\nStudies included \nStudy Timeframe Population Methods \nFour  KAP surveys  in the general  population   \nincludin  g LGBTQ+ \nEmory  conducte  d a o ne-time  KAP survey  of\n2021  AMIS  population  . \nSurvey  available  here \nOngoin  g recruitment  of the 2022  AMI  S \nsurvey  summarized  through  12/31 \nCross-sectional  survey  among  PEH t o \nunderstand  vaccine  acceptabilit  y an  d \noverage Port\ner Novelli August  – \nDecember  16  N= up to  371 LGBTQ+  \nData  weighted to   match  \ncensus  population \nAug 9th  – \n15th  November\nAMIS :Ameri\ncan   August 5   – \nAugust 15  N = 824 GBMSM  \nMen’s Internet  \nSurvey \nOctober  6 – N=3041 GBMSM  \nDecember  31 \n San  Francisco  study \n amon\ng persons  \n exp\neriencing c\n homelessness (PEH)   \n \n  AMETH\nST:Ame rican \n Transformative  HIV \nStudy N=8,551 \n50% Blac  k and  Latinx  \nGBMSM Mo nthly  cross-sectional  survey  to recruit  \nnew  cohorts  of persons  at risk for HIV . \nQuestions  related  to mpox added  in 2022 \nOct2\n3rd  – \n5th  November N= 273 \n 5\n7   wi th higher  risk  sexual \nactivity \n 35 GBMSM \n   \n \n      \n \n    \n     \n       \n  \n   \n  \n  \n \n      \n      \n   \n   \n    \n         \n   \n    \n    \n     \n          \n       \n   \n           Concern for mpox disease \nAMIS 2022 \n This survey has been recruiting since \nOctober 6th 2022 \n As of December 31, 2022 \n• 3041 cis-gender MSM have been enrolled \n• 33.3% (n=1006) had received at least one \ndose of mpox vaccine \n Mpox vaccination associated with \n• Mpox awareness, \n• Mpox concern, \n• STI risk, \n• and engagement in sexual health and prevention services Variable Adjusted* OR (95% CI) P value \nAny mpox vaccination \nHIV+ 1.66 (1.30, 2.11) <.01 \nHigh Mpox awareness 4.69 (3.94, 5.59) <.01 \nHigh Mpox concern 3.52 (2.69, 4.62) <.01 \nSTI testing 2.57 (2.12, 3.11) <.01 \nRecent CAS 1.76 (1.31, 2.37) <.01 \nPrEP use (ever)** 7.44 (6.07, 9.13) <.01 \nPrEP use (past year)** 2.80 (1.40, 5.61) <.01 \n* Adjusted models included age group (15-20, 21-24, 25-34, 35-44, \n45-59, 60+) and race/ethnicity (Hispanic, Non-Hispanic white, Non-\nHispanic Black, Other) \n** PrEP models considered for people at risk for HIV acquisition \n(HIV-negative) \n\nStudies included \nStudy Timeframe Population Methods \nPorter Novelli August – \nDecember 16 N= up to 371 LGBTQ+ \nData weighted to match \ncensus population Four KAP surveys in the general population \nincluding LGBTQ+ \nAMETHST :Ame rican \nTransformative HIV \nStudy Aug 9th – \nNovember 15th N=8,551 50% Black and Latinx \nGBMSM Monthly cross-sectional survey to recruit \nnew cohorts of persons at risk for HIV. \nQuestions related to mpox added in 2022 \nAMIS :American \nMen’s Internet \nSurvey August 5 – \nAugust 15 N = 824 GBMSM Emory conducted a one-time KAP survey of 2021 AMIS population. \nSurvey available here \nOctober 6 – \nDecember 31 N=3041 GBMSM Ongoing recruitment of the 2022 AMIS \nsurvey summarized through 12/31  \n  \n      \n    \n        \n \n  \n   \n          \n        \n     \n  \n               \n   \n  \n  \n        \n   \n   \n  \n \n  \n  \n     \n      \n    San Francisco study Oct 23rd – N= 273 Cross-sectional survey among PEH to \namong persons November 5th 57 with higher risk sexual understand vaccine acceptability and \nexperiencing activity coverage \nhomelessness (PEH) 35 GBMSM \n\n     \n     \n   \n    \n  \n \n   \n Overview of San Francisco Mpox Study \n Dates: October 23 – November 5, 2022 \n Project  Goals: \n1\n. Understand mpox vaccine \nacceptability and coverage among people experiencing homelessness \n2. Characterize orthopoxvirus seroprevalence among people experiencing homelessness \n\n        \n   \n   \n    \n  \n 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% \nAny higher risk \nsexual activity (n=57) \nGBMSM (n=35) Any higher risk \nsexual activity (n=57), 56% \nGBMSM (n=35), 74% \n          Vaccine acceptance by subgroups at higher risk for mpox \nWould accept or had accepted vaccine Unsure Would decline or had declined vaccine \n\n  \n  \n  \n \n \n \n \n \n \n  \n \n \n \n   \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n  \n    \n \n \n \n \n \n \n \n \n \n \n \n \n \n \n     \n   \n Acknowledgements \n SERMO \n• Joanna Molke (SERMO) \n• Ma\nnsi Das (CDC) \n Porter  Novelli \n• Fred Fridinger \n• Christine Prue \n• Guila Earle-Richardson \n• Christine Agnew-Brune \n• Saskia Vos \n• Ciara Nestor \n• Gordon Mansergh \n• Deborah Gelaude \n AMIS (Emory University) \n• Travis Sanchez \n• Patrick Sullivan \n• Marissa Hannah \n• O. Winslow Edwards  AMIS (Johns Hopkins University)  AMETHST \n• Stefan Baral \n• Tom Carpino \n• Kaitlyn Atkins \n• Evan Eschliman \n• Amrita Rao \n• Sarah  Murray \n AMIS (CDC) \n• Alexandra Oster \n• Christine Agnew-Brune \n• Winston Abara \n• Neal Carnes \n• Rachel Kachur \n• Kaytlin Renfro \n• Elizabeth DiNenno \n• Amy Lansky \n• Kathleen Ethier • Christian Grov \n• Adam Carrico \n• Denis Nash \n• Drew Westmoreland \n• Viraj Patel \n• Tyler Bartholomew \n• Jennifer Manuzak \n• Dustin Duncan \n• Kathryn McCollister \n• Meredith Ray \n• Matthew Stief \n• Alexa D’ Angelo \n• Chloe Mirzayi \n• Michelle Dearolf \n• Sarah Kulkarni \n• Alyse Johnson \n• Leah Davis Ewart \n• Yan Guo \n CDC 2022 Multinational Mpox \nOutbreak Response Community Engagement Taskforce", "summary": "x Information on Mpox vaccine acceptability and uptake from cross- sectional surveys  Kevin P . Delaney, PhD, MPH  Community Engagement and Vaccine Policy and Implementation Task Force 2022 Multinational Mpox Response Centers for Disease Control and Prevention  Advisory Committee on Immunization Practices  February 22, 2023  www.cdc.gov/mpo  Information from US-based Clinicians   Sermo – online community of >1.3 million clinicians   Conducted a worldwide survey of physicians  July 31-August…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/Mpox-05-Delaney-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 26}
{"title": "Mpox 06 Carter 508", "content": "Mpox Vaccine Implementation and Interim Clinical \nConsiderations \nRosalind Carter, PhD \nVaccine Task Force \n2022 Multinational Mpox Response \nCenters for Disease Control and Prevention \nAdvisory Committee on Immunization Practices \nFebruary 22, 2023 \nwww.cdc.gov/mpo x\n       \n          \n          \n          \n        \n      \n            \n             \n            \n   Interim Clinical Considerations (ICC) is a living \ndocument \n• Continued emphasis on vaccination : Mpox vaccination should continue to be \noffered to people with the highest potential for exposure to mpox . \n• Updated guidance : People with HIV infection or other causes of \nimmunosuppression who have had recent or anticipate potential mpox \nexposure should be vaccinated against mpox. \n• New emphasis on inclusion of adolescents : The principal risk group was \nreworded as “Gay, bisexual, and other men who have sex with men, and transgender or nonbinary people (including adolescents who fall into any of the aforementioned categories) … “ \n    \n     \n          \n  \n       \n    \n         \n      \n       Available Vaccines for Mpox \n• JYNNEOS \n• Primary vaccine for mpox outbreak in U.S. \n• Licensed in the U.S. for subcutaneous administration in individuals 18 \nyears or older \n• FDA Expanded Use Authorization (EUA) in Aug 2022 \n• Intradermal administration for individuals 18+ \n• Subcutaneous administration for individuals <18 at high risk for mpox infection \n• ACAM2000 \n• Available, but not used during current outbreak \n• Higher risk of serious adverse events, including myocarditis \n\n    \n    \n  \n     \n    \n   \n     \n   \n   \n   \n  \n    U.S. National Mpox Vaccine Strategy \n• U.S. National Mpox Vaccine \nStrategy – June 2022 \n Vaccinate and protect people at risk \n Prioritize vaccine allocations based \non reported case numbers \n Provide guidance to health officials \nfor planning and response \n• Multiple federal agencies \ncoordinating to implement mpox vaccine strategy \n ASPR (SNS, BARDA), CDC, FDA \n\n \n Strategy \t \ne \u000b\f\r \u000b\u000e  \nVaccination  Prior   to Exposure  Vaccination before  exposure  to  mpox Vaccination Strategies \nPost-Exposure Prophylaxis   (PEP) Vaccination   after known or presumed  exposure \nto  mpox \n \n              \n           \n     \n               \n   \n             \n             \n \n      \n      \n           \n Post-Exposure Prophylaxis \n• People who are known contacts to a person with mpox, and identified by public \nhealth authorities as a “contact” (for example, from case investigation, contact tracing, or risk exposure assessment); or \n• People who are aware that a recent (within the past 14 days) sex partner was diagnosed with mpox; or \n• Gay, bisexual, other men who have sex with men, and transgender or nonbinary people (includes adolescents) who have had any of the following within the past 14 days: \n sex with multiple partners (or group sex); \n sex at a commercial sex venue; or \n sex in association with an event, venue, or defined geographic area where mpox \ntransmission is occurring \n     \n               \n                 \n       \n              \n    \n            \n      \n               \n       \n               \n           \n                      \n                \n                            \n                 Vaccination prior to exposure to mpox virus \nOffered to people with highest potential for exposure or who anticipate potential exposure to mpox , including: \n• Gay, bisexual, and other men who have sex with men, and transgender or nonbinary people (including adolescents) \nwho, within the past 6 months, have had: \n A new diagnosis of one or more sexually transmitted diseases (e.g., chlamydia, gonorrhea, syphilis); or \n More than one sex partner. \n• People who have had any of the following in the past 6 months : \n Sex at a commercial sex venue; or \n Sex in association with a large public event in a geographic area where mpox transmission is occurring. \n• Sexual partners of people with the above risks. \n• People with HIV†infection or other causes of immunosuppression who have had recent or anticipate potential \nmpox exposure \n• People in certain occupational exposure risk groups (laboratory personnel working with orthopoxviruses) \n*People at risk for occupational exposure to orthopoxviruses include research laboratory personnel working with orthopoxviruses, clinical laboratory personnel performing diagnostic testing for orthopoxviruses, \nand orthopoxvirus and health care worker response teams designated by appropriate public health and antiterror authorities. (see ACIP recommendations). \n†JYNNEOS is considered safe in persons with HIV infection, although effectiveness may be lower among severely immunocompromised individuals. ACAM2000 should not be used in certain people, including those \nwith advanced HIV disease or other causes of immunosuppression, who are pregnant, or who have certain heart conditions. \n    \n \n        \n   \n         \n       \n         \n       \n       \n       \n     \n         CDC Health Equity Considerations Utilized in Mpox \nNational Vaccination Strategy \n• Engage people from affected communities in planning and design \n• Use non-stigmatizing, plain language \n• Reiterate privacy of information and how data will be used \n• Engage diverse partners already working with special populations \n• Bring vaccines to where people are: pop-up events, mobile outreach \n• To improve accessibility, offer multiple opportunities and times \n• Leverage clinical venues: STI clinics, LGBTQ+ health centers \n• Use multiple channels to advertise and book appointments \n• Minimize systems that are first-come, first-served \nMpox Vaccine Equity Toolkit | Mpox | Poxvirus | CDC \n      \n        \n        Doses administered 100,000 \n80,000 \n60,000 \n40,000 \n20,000 120,000 \n5/22-5/28\n5/29-6/4\n6/5-6/11\n6/12-6/18\n6/19-6/25\n6/26-7/2\n7/3-7/9\n7/10-7/167/17-7/237/24-7/30\n7/31-8/68/7-8/13\n8/14-8/20\n8/21-8/27\n8/28-9/3\n9/4-9/10\n9/11-9/17\n9/18-9/24\n9/25-10/110/2-10/8\n10/9-10/15\n10/16-10/2210/23-10/29\n10/30-11/5\n11/6-11/12\n11/13-11/19\n11/20-11/26\n11/27-12/3\n12/4-12/10\n12/11-12/17\n12/18-12/24\n12/25-12/31\n1/1-1/7\n1/8-1/14\n1/15-1/211/22-1/28\n1/29-2/6 First doses \nSecond doses EUA for intradermal administration introduced \n0           Total JYNNEOS Vaccine Doses Administered and \nReported to CDC as of Feb 7, 2023 \n1,185,907 doses* administered and reported to CDC since May 20, 2022 \n                        Vaccine First Doses Administered, by Race/Ethnicity \nData Reported to CDC as of January 31, 2023 \nWhite NH Hispanic or Latino Black NH Asian NH Other NH Multiple NH AI/AN NH NH/OPI NH \n100% Percent of first doses 90% \n80% \n70% 60% \n50% \n40% 30% \n20% \n10% \n0% 7% 9% \n7% \n16% \n61% 8% \n7% \n19% \n62% 8% \n13% \n23% \n51% 7% \n13% \n23% \n51% 7% \n12% \n22% \n51% 7% \n12% \n24% \n51% 7% \n12% \n24% \n49% 6% \n12% \n26% \n48% 7% \n13% \n26% \n47% 12% \n23% \n51% \nOverall \n5/22-6/18 \n6/19-7/16 7/17-8/13 \n8/14-9/10 9/11-10/8 10/9-11/5 11/6-12/3 \n12/4-12/31 \n1/1-1/28 \n                    \n              NH=non-Hispanic, AI/AN=American Indian/Alaska Native, NH/OPI=Native Hawaiian/Other Pacific Islander. W eeks where n<30 are not shown. Does not include recipients of Unknown race/ethnicity. \nSource: CDC Immunization Data Lake. Data submitted as of January 31, 2023, 4:00 am ET. \n124 \n       \n   \n           \n    \n            \n        \n           \n          \n           \n        \n            \n         \n              \n         \n             Elements of Mpox Vaccine Implementation in the \nU.S. during this Outbreak \n• Vaccine strategies and implementation plans were adapted by local jurisdictional health \ndepartments for their specific settings \n• Vaccine eligibility criteria were modified as the epidemiology evolved and new scientific findings emerged, and were adjusted for local context \n Examples: Inclusion of sex workers; removing sexual orientation labels from eligibility criteria, reducing potential stigma by allowing participant to self-attest to eligibility \n• Recognition that mpox vaccination offered in context of broader prevention activities and sexual health care may increase access and coverage \n• Critical role of community organizations as trusted messengers, facilitating increased access to vaccination \n• Need dedicated resources for reporting vaccine inventory and administration data \n• Require vaccine status, date of vaccination on mpox case reporting or link cases with state immunization inventory system to evaluate vaccine performance \n• Include race and ethnicity data on vaccination reports, including on reports shared with CDC \n   \n              \n          \n       \n               \n \n          \n          \n           \n   \n       Implementation challenges and solutions \n• Limited vaccine supply at the peak of the outbreak in mid-July when demand was \nhighest \n• EUA for intradermal route of administration increased vaccine supply by 300% \n• Limited ability to ship directly to providers \n• May to September, shipments limited to 5 per week; by mid Sept, up to 150 shipments/week \n• Switch to intradermal administration required skills training and additional supplies \n• On average, jurisdictions began to implement within 2-3 weeks of EUA \n• Initially, health departments and public clinics were the primary vaccine providers (>50% of all vaccinations) \n• Increasing role of STI, HIV care providers, pharmacies", "summary": "Mpox Vaccine Implementation and Interim Clinical  Considerations  Rosalind Carter, PhD  Vaccine Task Force  2022 Multinational Mpox Response  Centers for Disease Control and Prevention  Advisory Committee on Immunization Practices  February 22, 2023  www.cdc.gov/mpo x                                                                                                     Interim Clinical Considerations (ICC) is a living  document  • Continued emphasis on vaccination : Mpox vaccination should…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/Mpox-06-Carter-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 12}
{"title": "Mpox 07 Rao 508", "content": "National  Center  for Emerging  and Zoonotic  Infectious  Diseases \nEvidence to Recommendations Framework: \nVaccination with JYNNEOS During Mpox Outbreaks \nAgam Rao, MD \nCAPT, US Public Health Service \nPoxvirus and Rabies Branch \nCenters for Disease Control and Prevention \nAdvisory Committee on Immunization Practices \nFebruary 22, 2023 \nEvidence  to Recommendations  Framework \n    \n         \n  \n        \n    Evidence to Recommendations (EtR) Framework \n \n Structure to describe information considered in moving from evidence to \nACIP vaccine recommendations \nProvide transparency around the impact of additional factors on \ndeliberations when considering a recommendation \n\n \n        \n        \n      \n       \n              \n         \n      \n          \n     \n          EtR Domains \nEtR Domain Question(s) \nPublic Health Problem • Is the problem of public health importance? \nBenefits and Harms • How substantial are the desirable anticipated effects? \n• How substantial are the undesirable anticipated effects? \n• Do the desirable effects outweigh the undesirable effects? \nValues • Does the target population feel the desirable effects are large relative to the undesirable \neffects? \n• Is there important variability in how patients value the outcome? \nAcceptability • Is the intervention acceptable to key stakeholders? \nEquity • What would be the impact of the intervention on health equity? \nFeasibility • Is the intervention feasible to implement? \nResource Use • Is the intervention a reasonable and efficient allocation of resources? \n\n          \n         \n       \n                \n                \n                 \n     EtR question \nDoes ACIP recommend the 2-dose* JYNNEOS vaccine series for persons \naged 18 years and older at risk of mpox during an mpox outbreak?§ \n*Dose 2 administered one month after dose 1 \n§ Public health authorities determine whether there is an mpox outbreak; a single case may be considered \nan mpox outbreak at the discretion of public health authorities. Other circumstances in which a public \nhealth response may be indicated include ongoing risk of introduction of mpox into a community due to \ndisease activity in another geographic area. \n\nEtR Domain:   Public  Health  Problem \n     \n   \n  \n   \n   \n   \n \n    \n     \n  \n   \n  \n   \n   \n  \n  \n  \n   \n              \n                \n             Timeline of Notable Human Mpox Events* Multinational \noutbreak \nImported human cases to UK and US: 3 Imported Imported \ncases to UK cases to UK, \nand Israel: 3 Singapore: 2 \n-First human case identified -Rural settings US outbreak from pet prairie dogs (cohoused with infected small mammals from Ghana): 47 cases \nOutbreak in Nigeria involving 17 states: 138 cases \n1970 2003 2017 2018 2019 2021 2022 \n*During 1970-2021, mpox was endemic in 9 African countries: Cameroon, Central African Republic, Cote d’Ivoire, \nDemocratic Republic of Congo, Gabon, Liberia, Nigeria, Republic of Congo, and Sierra Leone; during recent years, there has been a re-emergence of human cases after decades of no reported cases \n\n       U.S. mpox case trends as of February 9, 2023 \n\n      \n    \n        \n   \n      \n          \n     \n    \n    \n     \n  \n        Many contacts monitored during investigations and \nsome secondary cases have occurred \n United States, July 2021: Traveler returning from Nigeria \n– 223 contacts monitored \n– No high-risk exposures and no secondary transmissions \n– Contacts included flight crew and fellow passengers on international and \ndomestic flights, friends, Ride-share driver \n United Kingdom, 2019 and 2021 \n– 2019: Healthcare personnel developed mpox \nafter presumed exposure while changing \nbedding of mpox patient \n– 2020: Two household contacts of mpox patient developed mpox \n\n   \n  \n  \n \n \n \n Typical manifestations of mpox \nFro  m Basgoz N  , Brown  CM , Smole  SC , e t al . Case  24-\n2022  :  A 31-Year-Old  Man  with  Periana  l and  Penile  Ulcers  , \nRecta  l Pain  , and  Rash  . Epub ahead  of  print  . Copyrigh  t © \nJun  15  2022  . Massachusetts  Medica  l Society  . Reprinted  \nwith  permission  fro m Massachusetts  Medica  l Society \nAbove  :  Shared  with  permission  fro m \npatients \n• Lesions often \nperianal and/or \naffecting genitals \n• Rectal pain \n• Abdominal pain \n• Rectal bleeding \n• Tenesmus \nhttps://www.cdc.gov/mmwr/volumes/71/wr/mm7132e3.htm?s_cid=mm7132e3_w \n\n     \n      \n  \n  \n \n \n \n        \n          \n             \n         \n        \n     \n  \n  \n  \n \n  \n   \n  \n \n  \n   Severe manifestations: Ocular lesions, neurologic \ncomplications, myopericarditis, and some mucosal lesions \nLeft: Keratitis \nand conjunctival \nulcer \nComplications \nassociated with \nsome mucosal \nlesions \n• Painful or Above: \nencephalitis obstructing \nrectal, urinary Right: \ntract, oral and transverse \nmyelitis genital lesions \nand strictures \n• Lesions might expose muscle or \nbone \nCole J, Choudry S, Kular S,et al. Monkeypox encephalitis with transverse \nmyelitis in a female patient. Lancet Infect Dis. 2022 Dec 2:S1473-\nRodriguez-Nava  G, Kadlecik P, Filardo  TD et al. Myocarditis  Attributable  to Monkeypox  Virus  \nInfection  in 2 Patients,  United  States, 2022.  Emerg Infect  Dis. 2022  Dec;28(12):2508-2512. 3099(22)00741-1. \nCash Goldwasser  S,   Labuda  SM, McCormick  DW et al. (2022  ) \nOcular  monkeypox, United  States—July-September  2022  . \nMMWR.  2022  Oct \nAbove: NSR with TWI in inferior and anterolateral leads of ECG. Patient \nwith mpox and no underlying medical conditions. Other signs and symptoms: SOB, decreased exercise tolerance, elevated Tn (0.35ng/mL reference <0.07 ng/mL) indicating myocarditis \n\n          \n            \n         \n       \n        \n       Severe  manifestations  from uncontrolled viral spread  i n \nseverely  immunocompromised  patients \nMenezes YR, Miranda AB. Severe disseminated clinical \npresentation of monkeypox virus infection in an immunosuppressed patient: first death report in Brazil. Rev Soc Bras Med Trop. 2022 Aug 29;55:e0392. Carrubba S, Geevarghese A, Solli E et al. Novel severe oculocutaneous manifestations of human monkeypox virus infection and their historical analogues. Lancet Infect Dis. 2023 Jan 23:S1473-3099(22)00869-6. \n\n  \n  \n     Public health importance \nWork group interpretation \nAre outbreaks of mpox of public health importance? \n\nEtR Domain:   Benefits  and Harms \n      \n \n           \n           \n               \n              \n         \n \n        \n             \n        \n            \n            \n       Early Estimates and Population-based, adjusted VE \nmeasures* \n Vaccine performance \n– Comparison of incidence between vaccinated and unvaccinated persons in 43 U.S. \njurisdictions: Mpox incidence among unvaccinated was 7.4 (95% CI=6.0-9.1) times that \namong persons who received only 1 dose of JYNNEOS vaccine ≥14 days earlier, and 9.6 \n(95% CI = 6.9–13.2) times that among persons who received dose two ≥ 14 days \nearlier \n Population-based, adjusted measures of vaccine effectiveness (VE) using electronic \nmedical records \n– Retrospective, population-based cohort study conducted in Israel; 5 mpox infections \namong subjects vaccinated with 1 SC dose and 16 among unvaccinated subjects. VE \nfor dose 1 was 86% (95% CI = 59-95%) \n– Nationwide U.S. case-control study with 1:4 ratio of cases matched to controls; \nadjusted VE was 35.8% (95% CI: 22.1-47.1%) for one dose and 66.0% (95% CI: 47.7 -\n78.1%) for 2 doses, regardless of vaccination route \n\n     \n \n       \n            \n           \n           \n           \n      Early Estimates and Population-based, adjusted \nVE measures* \n Population-based, adjusted measures of VE using case-control studies \n– Case-control study of adult MSM (18-49 years of age) in 12 U.S. jurisdictions; \nadjusted VE was 76% (95% CI: 48-89%) for two doses (interim results) \n– New York State case-control study of adult male mpox cases matched to STI controls; adjusted VE was 68% (95% CI: 25-86%) for one dose and 89% (95% CI: 44-98%) for two doses (preliminary results) \n\n      \n         \n        \n           \n          \n            \n           \n        PEP effectiveness and infections following single dose \n France: 10% (11 of 108) of those administered JYNNEOS after mpox \nexposure became symptomatic with mpox disease soon after vaccination \n(IQR 1-6, median 5 days), although clinical course mild among those \npersons \n France: Observational study involving people who received single, SC dose; 4% (12 of 276) infected during month after vaccination, none with serious \ninfection \n NYC: Cohort study of individuals with high-risk exposure; VE was 77% with PEP <14 days after last exposure and 79% with PEP <14 days after first exposure \n\n  \n       \n   Benefits \nWork group interpretation \nHow substantial are the desirable anticipated effects of mpox \nvaccine during an outbreak? \n\n    \n            \n         \n        \n  \n         \n      \n          \n \n      Vaccine Safety: Subcutaneous administration \n During May 22, 2022 –January 13, 2023, a total of 1,125,168 JYNNEOS \nvaccine doses were administered. CDC monitored JYNNEOS safety using \nVAERS and VSD for vaccine recipients of all ages \n Adverse events (AEs) \n– The most common AEs reported were nonserious and included \ninjection site reactions, consistent with prelicensure studies \n– Reported at similar rates for doses received by intradermal and \nsubcutaneous administration \n– Serious adverse events were rare among adults \n\n  \n       \n   Harms \nWork group interpretation \nHow substantial are the undesirable anticipated effects of \nmpox vaccine during an outbreak? \n\n  \n  \n        \n  \n       \n                                      \nDo the desirable effects outweigh the undesirable effects? \nFavors intervention Favors comparison Favors both Favors neither Unclear Benefits / Harms \nWork group interpretation \nWhat is the balance between the desirable effects relative to \nthe undesirable effects? \n\nEtR Domain:   Values \n      \n      \n           \n   \n          \n       \n   \n          \n     \n         \n         \n            \n          Vaccination values extrapolated from 2022 outbreak data \n Populations at highest risk concerned about mpox \n– In August, 53.1% of American Men’s Internet Survey (AMIS) respondents had \nconcerns about getting mpox \n– During October-December, an AMIS survey showed that those with high mpox concern had 3.5 times odds of being vaccinated \n Interest in vaccine high \n– During Aug-Nov, >85% of respondents in the American Transformative HIV Study (AMETHST) were interested in vaccine \n– During Aug-Dec, 50% of Porter-Novelli survey responders who identified as LGBTQ+ felt that vaccination is important to protect from mpox \n– During Oct-Nov, >70% of MSM in a San Francisco survey of persons experiencing homelessness reported that they would accept or have accepted vaccination \n\n  \n  \n        \n    \n Does  the targe  t population  feel that  the desirable  effects  are large  relative  to  \nundesirable  effects \nNo            Probably  no            Uncertain            Probably  ye s          Yes Varies Target population sentiments \nWork group interpretation \nDoes the target population feel that the desirable effects are \nlarge relative to undesirable effects? \n\n        \n \n         \n    \n          \n   \n          \n          \n  Uncertainty or variability in how much people might \nvalue vaccination \n During 2022 mpox outbreak, willingness to be vaccinated was dynamic, \nand dependent on perceived vulnerabilities \n There is clear demand for JYNNEOS vaccination, but many remain unvaccinated for unclear reasons \n Demographics of future outbreaks unclear; unknown if values expressed by population most affected by the 2022 mpox outbreak can be extrapolated to all other populations \n\n  \n  \n         \n    \n         \n           Possib  ly important\n  uncertainty  or          \n  variability             Pr obably  no     \nimportan  t          \nuncertainty  or   \nvariabilit  y         No impor tant\n  uncertainty   or  \n  variabilit  y                    No kn own \n undesirable \n  outcomes    \n                       \n                 Target population sentiments \nWork group interpretation \nIs there important uncertainty about or variability in how much \npeople value the main outcomes? \nIs there  important  uncertainty  about  or\noutcomes vari ability in how much people value the main \nImportan  t    \nuncertaint  y     \nor variabilit  y     \n\nEtR Domain:   Acceptability \n     \n     \n         \n      \n   \n       \n      \n       \n \n       \n   Stakeholder perceptions: Sermo survey of clinicians \n Sermo*: Online community of >1.3 million \nclinicians \n July 31 - August 1, 2022 survey results of U.S. \nclinicians (n=415): 69% felt U.S. without enough mpox vaccine to handle outbreak \n September 12, 2022 survey of U.S. clinicians \n(n=62) \n• 66% had treated at least one mpox patient \n• 76% knew where a patient could get \nJYNNEOS vaccination \n• 86% wanted to be able to provide vaccination in their office *\nhttps://app.sermo.com/barometer/unitedstates \n\n    \n        \n Stakeholder perceptions: Health departments \n Health departments have been requesting JYNNEOS and organizing \nvaccination campaigns \nhttps://aspr.hhs.gov/SNS/Pages/JYNNEOS-Distribution.aspx \n\n   \n      \n     \n \n     \n \n   \n    \n \n     \n Vaccine equity pilot program \n Enabled jurisdictions to request more than \ntheir allotted amount of JYNNEOS vaccine \n Established to \n– Support innovative ways to address \nvaccination disparities \n– Encourage vaccination coordination between health departments and community-based organizations \n– Promote innovation to strengthen existing vaccination infrastructure \n\n  \n     Acceptability \nWork group interpretation \nIs the intervention acceptable to key stakeholders \n      \n                                               Is the intervention acceptable to key stakeholders \nNo Probably no Uncertain Probably yes Yes Varies \nEtR Domain:   Resource  Use \n \n         \n         \n        \n        \n      Resource Use \n JYNNEOS vaccine is provided from HHS’ Strategic National Stockpile (SNS) \nfree-of-charge \n Vaccines are a good use of resources during an outbreak \n Costs and challenges associated with mobile, pop-up vaccination sites \n Cost-effectiveness analysis of vaccine implementation during the current outbreak planned, but not currently available \n\n \n  \n        Resource Use \nWork group interpretation \nIs the intervention a reasonable and efficient allocation of \nresources \n         \n                                               Is the intervention a reasonable and efficient allocation of resources \nNo Probably no Uncertain Probably yes Yes Varies \nEtR Domain:   Equity \n          \n \n    \n        \n         \n         \n         \n   Equity \n No groups or settings disadvantaged by recommendation for JYNNEOS use \nduring mpox outbreaks \n Effectiveness same for all immunocompetent persons \n Implementation to assure equitable access will be important particularly among persons who are at high risk for severe outcomes \n Might facilitate broad acceptance of the recommendation (e.g., by insurance companies, health departments) because endorsed by ACIP after rigorous review of evidence \n\n  \n       \n       \n                                                  \n                                                      Equity \nWork group interpretation \nWhat would be the impact on health equity \nWhat would be the impact on health equity? \nReduced Probably Reduced Probably no impact \nIncreased Varies Don’t know Probably increased \n\nEtR Domain:   Feasibility \n        \n      \n    \n \n       \n  \n       \n     Feasibility \n Feasibility of conducting vaccine campaigns in communities, at events, \nand within public health facilities demonstrated in 2022 \n Can be integrated into providers’ practices \n– Standing orders available \n– Immunization Information Systems requirements for reporting vaccinations \nsame as COVID-19 vaccines \n– JYNNEOS can be stored refrigerated for 8 weeks \n Wide range of vaccinators can administer JYNNEOS \n\n \n     \n     \n   \n \n    \n    \n  \n  \n    WG discussions \n JYNNEOS vaccination probably sustainable during outbreaks \n Vaccine access is an important concern \n– Increased and convenient access \n– Low stigma \n Considerations to ensure vaccine equity \n– Strong ties with community-based organizations \n– Support vaccination events \n– Engage trusted messengers \n– Ensure access (including in rural areas) \n\n  \n    \n     \n                                                  Feasibility \nWork group interpretation \nIs the intervention feasible to implement? \nIs the intervention feasible to implement \nNo Probably no Uncertain Probably yes Yes Varies \n\n  \n   \n   \n \n     \n  \n  \n     \n  \n   \n  \n \n    \n  \n    \n \n \n   \n         \n  \n    \n    \n  \n Summary of EtR #1 \nDomains Domains Domains \nBenefits: How \nsubstantial are the desired \nanticipated effects Large Values: Does the \ntarget population feel desirable \neffects are large Probably \nYes Impact on health equity Probably increase d \nHarms: How substantial are undesirable \nanticipated \neffects? Small Is there important uncertainty about or variability in \nvalues? Possibly \nimportant uncertainty \nor \nvariability Feasible to implement? Yes \nBenefit / Harm: Favors intervention Acceptable to stakeholders? Yes Balance of consequences: \nOverall certainty of the evidence for the critical \noutcomes Moderate Reasonable and \nefficient allocation of resources? Varies \n\n  \n                       Undesirable \nconsequences  probab  ly \noutweigh  desirable          \nconsequences  in most    \nsettings                                \n                               \n                                 \n             \n             \n             \n             Balance of Consequences \nUndesirable                  \nconsequences  clear  ly   \noutweigh  desirable        \nconsequences  in mos  t  \nsettings Balance  between  \n   desirable  and undesirable\n   consequences  is close  ly \n balanced  or uncertain  \nDesirable  consequence  s     \nprobably  outweigh                \nundesirable  consequence  s \nin mos  t setting  s                    X  Des irable  consequences \n clearl  y outweig  h   \n undesirable  consequence  s        \n in mos  t settings There  is insufficient  evidence \nto determine  the balance  of \n  consequences \n\n \n         \n        \n       \n               \n               \n                \n     Proposed wording \nACIP recommends the 2-dose* JYNNEOS vaccine series for persons \naged 18 years and older at risk of mpox during an mpox outbreak§ \n*Dose 2 administered one month after dose 1 \n§ Public health authorities determine whether there is an mpox outbreak; a single case may be considered \nan mpox outbreak at the discretion of public health authorities. Other circumstances in which a public \nhealth response may be indicated include ongoing risk of introduction of mpox into a community due to \ndisease activity in another geographic area. \n\n \n            \n          \n       \n           \n            \n       Clinical Considerations \n In outbreak setting, vaccine is ideally given pre-exposure but may also be \ngiven as post-exposure prophylaxis (PEP) , although evidence not been \nreviewed by ACIP for PEP at this time \n Complete 2-dose vaccine series should be given regardless of timing of exposure \n Although ACIP has not reviewed the evidence, if there are vaccine supply shortages, ID route of administration can be used \n\n      \n   \n                Tentative timeline for ACIP discussions and votes* \nCurrent  U S mpox vaccination  strateg  y remains  active  :  Populations  \n3Curreantt   hUi.Sg. h  mripsoxk  vsahccoinulatid  ocn ostntriatneugy e  treo  mbaie  nsv ian cecfifnecatted \nFebruary 2023 June 2023 October 2023 \n*February 2023 and June 2023 votes do not impact existing recommendations for the current mpox outbreak.\n3https://www.cdc.gov/poxvirus/monkeypox/interim-considerations/overview.htmlMpox  outbreaks:  Use of 2-\ndose  JYNNEOS for person  s \naged  ≥ 18 years Mpox  outbreaks:  Use of 2-dose  JYNNEOS \nfor persons  aged  <18 year  s \n-Updates  about vaccine  effectiveness  an d\nsafetyCo nsider  need  for longer  ter  m \nvaccination  strategy for 2-dose  \nJYNNEOS  \n\n \n \n \n \n \n \n \n \n  \n \n \n \n \n \n \n \n \n Acknowledgements \n Amanda  Cohn \n Rosalind Carter \nKevin Delaney \n \n Catherine McLean \n Faisal Minhaj \n Sascha  Ellington \n Jonathan  Duffy \n Dani Moulia \n Anna  Chard \n Manisha  (Mo)  Patel   Adam Cohen  Saskia Voss \n Tom Shimabukuro  Dan Payne \n Rita Helfand  Michael Yeh \n Melinda Wharton  David Hopkins \n Emily Mosites  Brett Petersen \n Dan Filardo  Jane Zucker \n Grace Marx  Jennifer Rosen \n Amy Lansky  Eli Rosenberg \n Rachel Kachur  Sara Oliver \n Christine Prue  Robbie Goldstein \n\n    \n \n      \n                  \n         Questions? \nFor more information, contact CDC \n1-800-CDC-INFO (232-4636) TTY: 1-888-232-6348 www.cdc.gov \nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. \nNational  Center  for Emerging  and Zoonotic  Infectious Diseases \nDivision  of High-Consequenc  e Pathogens  and Pathology", "summary": "National  Center  for Emerging  and Zoonotic  Infectious  Diseases  Evidence to Recommendations Framework:  Vaccination with JYNNEOS During Mpox Outbreaks  Agam Rao, MD  CAPT, US Public Health Service  Poxvirus and Rabies Branch  Centers for Disease Control and Prevention  Advisory Committee on Immunization Practices  February 22, 2023  Evidence  to Recommendations  Framework                                 Evidence to Recommendations (EtR) Framework     Structure to describe information…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/Mpox-07-Rao-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 48}
{"title": "influenza 01 Talbot 508", "content": "Seasonal Influenza Vaccines \nH. Keipp Talbot , MD, MPH\nChair, Influenza Work Group \nAdvisory Committee on Immunization Practices \nFebruary 22, 2023  \nInfluenza Work Group \n\n Session Overview", "summary": "Seasonal Influenza Vaccines  H. Keipp Talbot , MD, MPH Chair, Influenza Work Group  Advisory Committee on Immunization Practices  February 22, 2023   Influenza Work Group    Session Overview", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/influenza-01-Talbot-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 3}
{"title": "influenza 02 Grohskopf 508", "content": "U.S. Influenza Activity \nLisa Grohskopf \nAdvisory Committee on Immunization Practices \nFebruary 22, 2023 \nVirologic Surveillance\n[\n\\\n]\n^ _\n]`[\n\\\n]\n` _\n]\na[\n\\\n]\na\n_\n[\n\\[\n\\\n[\n]\n_\n[[[\n\\\n[\n[\n_\n[\nb\n[\n\\\n[\n\\_\n[\n]c d\ne f\ng\nh\nd\ni\njf\nf\nk\nf\ng\nh\nl\ng\nm\nn o\no\np\nq\npf\nf\nk r\ns t\nu\nv\nw\nx\ny\n    \n \n      \n                        \n   For more information, contact CDC \n1\n-800-CDC-INFO (232-4636) \nTTY: 1-888-232-6348 ww\nw.cdc.gov \nTh\ne findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for \nDisease Control and Prevention.", "summary": "U.S. Influenza Activity  Lisa Grohskopf  Advisory Committee on Immunization Practices  February 22, 2023  Virologic Surveillance [ \\ ] ^ _ ]`[ \\ ] ` _ ] a[ \\ ] a _ [ \\[ \\ [ ] _ [[[ \\ [ [ _ [ b [ \\ [ \\_ [ ]c d e f g h d i jf f k f g h l g m n o o p q pf f k r s t u v w x y                                           For more information, contact CDC  1 -800-CDC-INFO (232-4636)  TTY: 1-888-232-6348 ww w.cdc.gov  Th e findings and conclusions in this report are those of the authors and do not…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/influenza-02-Grohskopf-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 7}
{"title": "influenza 03 Olson Lewis Tenforde 508", "content": "nlzation & Respi \nInterim Influenza Vaccine Effectiveness against \nInpatient, Emergency Department, and Outpatient \nIllness in the 2022-23 season \nData from the New Vaccine Surveillance Network (NVSN), \nFlu and Other Viruses in the Acutely Ill Network (IVY), \n& VISION Network \nSamantha Olson MPH, Nathaniel Lewis PhD, & Mark Tenforde MD PhD \nAdvisory Committee on Immunization Practices \nFebruary 22, 2023 \n    \n \n      \n                        \n   For more information, contact CDC \n1\n-800-CDC-INFO (232-4636) \nTTY: 1-888-232-6348 ww\nw.cdc.gov \nTh\ne findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for \nDisease Control and Prevention.", "summary": "nlzation & Respi  Interim Influenza Vaccine Effectiveness against  Inpatient, Emergency Department, and Outpatient  Illness in the 2022-23 season  Data from the New Vaccine Surveillance Network (NVSN),  Flu and Other Viruses in the Acutely Ill Network (IVY),  & VISION Network  Samantha Olson MPH, Nathaniel Lewis PhD, & Mark Tenforde MD PhD  Advisory Committee on Immunization Practices  February 22, 2023                                            For more information, contact CDC  1…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/influenza-03-Olson-Lewis-Tenforde-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 25}
{"title": "influenza 04 Mclean 508", "content": "Marshfield Clinic Research InstituteInterim Estimates of 2022─23 Influenza Vaccine Effectiveness from \nTwo Studies in Wisconsin: A Test -Negative Case- Control Study and a \nCommunity Cohort Study\nACIP Meeting | February 22, 2023\nHuong McLean presenting on behalf of the study team\nMarshfield Clinic Research Institute received support for this study from CSL Seqirus and CDC \n(75D30120C09259) \nTest-negative case- control study\n2\n•Enrollees: Outpatients aged 6 months –64 years with acute respiratory illness \nwith cough ≤7 days duration\n•Dates of enrollment: December 2, 2022 –February 10, 2023\n•Nasal and oropharyngeal swabs tested for influenza and SARS -CoV-2 \n•Vaccination status: documented (in health record) receipt ≥14 days before \nillness onset per ACIP recommendations \n•Analysis: VE = (1 –adjusted OR) x 100%\n‒Logistic regression model adjusted for age, month of onset, higher -risk condition \n(self report)Methods: Test- negative case -control study\n3\nRT-PCR results by week of enrollment \n4 1 patient was positive for both influenza and SARS -CoV- 2 and represented above as separate counts (week ending 12/24/2022) \n•34/34 sequenced A(H3N2) \nviruses belonged to subclade 2a2\n•9/9 A(H1N1pdm09) belonged to subclade 5a.2 \n\nParticipant* characteristics\n5Total no. of \npatientsNo. (%) \nvaccinated †No. (%) \ninfluenza positiveNo.(%) i nfluenza -and \nSARS -CoV-2 negative\nTotal 545 186 (34) 116 (21) 249 (79)\nAge 6 mos – 17 years 223 69 (31) 42 (19) 181 (81)\n18 – 64 years 322 117 (36) 74 (23) 248 (77)\nSex Female 318 127 (40) 65 (20) 253 (80)\nMale 227 59 (26) 51 (22) 176 (78)\nRace/ethnicity Non -Hispanic White 482 161 (33) 105 (22) 377 (78)\nHispanic 35 12 (34) 6 (17) 29(83)\nNon -Hispanic non- White 28 13 (46) 5 (18) 23 (82)\nSelf report of higher -\nrisk condition§Yes 154 69 (45) 30 (19) 124 (81)\nNo 391 117 (30) 86 (22) 305 (78)\nSelf report of ≥2 COVID -\n19vaccine doses Yes 258 133 (52) 51 (20) 207 (80)\nNo 287 53 (18) 65 (23) 222 (77)\n*109 patients had a positive test result for SARS -CoV- 2 virus infection and were excluded.\n†84% received cell -culture based vaccine (ccIIV4). \n§Based on self -report of asthma or another chronic lung disease, cancer, diabetes, heart disease including high blood pressure, i mmunocompromising \ncondition, kidney disease, liver disease, obesity, and pregnancy in the 12 months preceding enrollment.\nVaccine effectiveness (VE) against outpatient influenza, \nchildren and adults aged 6 months – 64 years\n6Influenza positiveInfluenza -and \nSARS -CoV-2 negativeAdjusted VE*\nNo. vaccinated / \nTotal%No. vaccinated / \nTotal% % (95% CI)\nInfluenza A 26 / 116 22 160 / 429 37 54 (23- 73)\nA(H3N2) 16 / 86 19 160 / 429 37 60 (25- 79)\nStudy period: December 2, 2022 – February 10, 2023.\n*VE was estimated using the test- negative design as 100% x (1 –aOR) where aOR represents ratio of odds of being vaccinated among influenza positive \ncases to odds of being vaccinated among influenza -negative and SARS -CoV- 2-negative controls; ORs were estimated using logistic r egression with \nadjustment for age, month of illness onset, and presence of one or more higher -risk condition. \nProspective community cohort study\n7\n•Ongoing community cohort in central Wisconsin\n•241 children aged 1 –1 7 years followed weekly since September 5, 2022\n•Weekly reporting for absence or presence of symptoms\nFever, cough, loss of smell or taste, sore throat, muscle/body aches, shortness of breath, \ndiarrhea, nasal congestion/runny nose, or nausea/vomiting\n•New symptom onset prompts self- o r guardian -collection of anterior nasal \nswab for influenza and SARS -CoV-2 testing \n•Information collected from surveys and extracted from electronic health \nr\necords (e.g., vaccination history, clinical influenza test results)Methods: Community cohort study\n8\n•Influenza case: positive RT -PCR influenza result (research or clinical sample)\n•VE = 𝟏𝟏−𝐚𝐚𝐚𝐚𝐚𝐚𝐚𝐚𝐚𝐚𝐚𝐚𝐚𝐚𝐚𝐚 𝑯𝑯𝑹𝑹𝒓𝒓𝒓𝒓𝒓𝒓𝒓𝒓𝒐𝒐𝒐𝒐𝒊𝒊𝒊𝒊 𝒐𝒐𝒊𝒊𝒊𝒊𝒓𝒓𝒊𝒊𝒊𝒊𝒓𝒓𝒊𝒊𝒊𝒊𝒐𝒐𝒓𝒓𝒊𝒊𝒓𝒓𝒊𝒊 𝒐𝒐𝒊𝒊𝒓𝒓𝒂𝒂𝒐𝒐 𝒊𝒊 𝒂𝒂𝒗𝒗𝒓𝒓𝒊𝒊 𝒊𝒊𝒊𝒊𝒊𝒊𝒓𝒓𝒓𝒓𝒓𝒓𝒗𝒗𝒑𝒑𝒓𝒓 𝒓𝒓𝒑𝒑𝒐𝒐 𝒊𝒊−𝒓𝒓𝒊𝒊 𝒂𝒂𝒓𝒓\n𝒓𝒓𝒓𝒓\n𝒓𝒓𝒓𝒓𝒐𝒐𝒐𝒐𝒊𝒊𝒊𝒊\n𝒐𝒐𝒊𝒊𝒊𝒊𝒓𝒓𝒊𝒊𝒊𝒊𝒓𝒓𝒓𝒓𝒂𝒂𝒐𝒐\n𝒊𝒊\n𝒂𝒂𝒊𝒊\n𝒊𝒊𝒗𝒗𝒓𝒓𝒊𝒊𝒊𝒊𝒊𝒊𝒊𝒊𝒓𝒓𝒓𝒓𝒓𝒓𝒗𝒗 𝒑𝒑𝒓𝒓\n𝒓𝒓𝒑𝒑𝒐𝒐\n𝒊𝒊−𝒓𝒓𝒊𝒊\n𝒂𝒂𝒓𝒓∗𝟏𝟏𝟏𝟏𝟏𝟏𝟏\n•A\ndjusted for age, higher -risk condition (self -report), COVID -19 vaccination Analysis: Community cohort study\n9At risk October 23, 2022 –February 10, 2023 or positive influenza infection date\nVaccinated ≥14 days after influenza vaccine receipt*\nUnvaccinated Time before influenza vaccination\nCensored Person -time for the 13 days after vaccine receiptCox proportional hazards model with time- varying vaccination status\n*Based on documentation in health record according to ACIP recommendations \nCharacteristics of community cohort\n10Total no. of \nparticipants*No. (%) \nvaccinated †No. (%) \ninfluenza positive¶\nTotal 241 94 (39) 34 (14)\nAge 1 –8 years 71 31 (44) 9 (13)\n9 –17 years 170 63 (37) 25 (15)\nSex Female 116 49 (42) 17 (15)\nMale 125 45 (36) 17 (14)\nRace/ethnicity Non -Hispanic White 233 92 (39) 33 (14)\nHispanic 2 2 (100) 1 (50)\nNon -Hispanic non- White 6 0 (0) 0 (0)\nSelf report of higher -risk\ncondition§Yes 31 13 (42) 6 (19)\nNo 210 84 (39) 28 (13)\n≥2 COVID -19vaccine doses Yes 115 61 (53) 20 (17)\nNo 126 33 (26) 14 (11)\n*242 participants enrolled; 1 was excluded because they were partially vaccinated per ACIP recommendations prior to the start ofthe analysis period.\n†84% received cell -culture based vaccine (ccIIV4). \n¶3 cases occurred ≤14 days from influenza vaccination and were censored at the time of vaccination. \n§Based on self -report of asthma, immunocompromised state, serious heart condition, or other chronic lung disease.\nInfluenza and SARS -CoV-2 infections by week of onset\n11\n•6/6 sequenced A(H3N2) \nviruses belonged to subclade 2a2 \n\nVaccine effectiveness (VE) against symptomatic influenza among children \n12No. of \ninfluenza \ninfections *No. of \nperson -daysIncidence per 1,000\nperson -daysAdjusted VE†\n% (95% CI)\nVaccinated 6 7,292 0.8271 (31 ‒ 90)Not Vaccinated 28 15,678 1.79\nStudy period: October 23, 2022 – February 10, 2023.\n*3 influenza infections were censored because onset occurred within 14 days of vaccination.\n† VE was estimated from Cox proportional hazards model with time -varying influenza vaccination status, age, presence of at least o ne higher -risk condition \n(self -report of asthma, immunocompromised state, serious heart condition, or other chronic lung disease), and receipt of 2 or mo re COVID -19 vaccine \ndoses before the analysis period. \n•Single geographic area (central WI)\n\n\n\n\nPredominant viruses similar in study population and across US\n•Adults aged ≥6 5 years excluded\nGenerally have lower VE estimates against A(H3N2) \n•Small sample sizes  \nWide confidence intervals\nUnable to estimate VE for A(H1N1)pdm09 or age groups\n•Confounding and bias with observational studies\nComparable estimates across two study designsLimitations\n13\n•Interim results indicate substantial vaccine- induced protection against \ninfluenza A during 2022 -23 season\n‒VE 54% against medically attended influenza A in children and working aged \nadults \n‒VE 71% against symptomatic influenza A in children\n•All characterized viruses from the study population belonged to the same \ngenetic subclade as the viruses included in the 2022 –23 Northern Hemisphere \ninfluenza vaccineSummary\n14\nJennifer King \nCarla Rottscheit \nAdam Bissonnette \nGina Burbey \nLiz Armagost \nBrooklyn Arbs \nSaydee Benz \nRiley Bonifer\nBobbi Bradley \nMichaela Braun \nBrianna Breu \nCorey -Beth Cielinski\nChristian Delgadillo \nLeila Deering \nHeather Dirkx \nRoxy Eibergen \nAlex Ermeling\nKelsey Ewert\nKallie Falteisek\nRachel Fernandez Hope Florence \nSandy Freeman \nWayne Frome\nTammy Gault \nEmily Gruenling\nSherri Guzinski \nAngela Harless \nMitch Hertel\nGarrett Heuer\nLee Jepsen\nJulie Karl \nBurney Kieke \nStephanie Kohl \nSarah Kohn \nDiane Kohnhorst \nSarah Kopitzke \nTamara Kronenwetter Koepel \nErik Kronholm \nKate Lassa \nThao LeAlaura Lemieux \nCarrie Marcis \nMegan Maronde\nDave McClure \nIsaac McCready \nAndrea McGaver\nKaren McGreevey \nNidhi Mehta \nLaura Michalik \nVicki Moon\nJennifer Moran \nMike Owens \nDeeAnn Polacek \nMartha Presson \nNicole Price \nMaxine Racanelli\nChris Rayburn \nMiriah Rotar \nJesse Rozmarynowski\nJackie SalzwedelJuan Saucedo \nKelly Scheffen \nAlex Slenczka\nJacob Solis \nElisha Stefanski \nMelissa Strupp\nLyndsay Watkins \nProviders, managers, \nand clinical staff at: \nMarshfield Clinic Lake Hallie \nCenter \nMarshfield Clinic Wausau Center \nMarshfield Medical Center -\nEau Claire\nMarshfield Medical Center -\nMarshfield\nMarshfield Medical Center -\nWestonAcknowledgements\n15\nEdward Belongia*\n Joshua Petrie*\n Kayla Hanson*\n Jennifer Meece*Marshfield Clinic Health System\nGregg Sylvester*\nKarita Ambrose\nAshesh Gandhi\nMendel HaagCSL Seqirus\nMelissa Rolfes*\nBrendan Flannery\nJessie ChungCDC\nGabriele Neumann*\nYoshihiro Kawaoka *\nDavid PattinsonUniversity of \nWisconsin – Madison\n*Coauthor", "summary": "Marshfield Clinic Research InstituteInterim Estimates of 2022─23 Influenza Vaccine Effectiveness from  Two Studies in Wisconsin: A Test -Negative Case- Control Study and a  Community Cohort Study ACIP Meeting | February 22, 2023 Huong McLean presenting on behalf of the study team Marshfield Clinic Research Institute received support for this study from CSL Seqirus and CDC  (75D30120C09259)  Test-negative case- control study 2 •Enrollees: Outpatients aged 6 months –64 years with acute…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/influenza-04-Mclean-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 15}
{"title": "influenza 05 Grohskopf 508", "content": "National Center for Immunization & Respiratory Diseases\nPublished Estimates of LAIV Effectiveness\nLisa Grohskopf\nAdvisory Committee on Immunization Practices\nFebruary 22, 2023\nUpdate on Published Estimates of LAIV4 Effectiveness: Background\nLAIV4 not recommended in the U.S. for 2016 -17 and 2017- 18, following \nobservation of poor effectiveness against H1N1pdm09 viruses.\nSubsequent studies suggested poor replicative fitness of the LAIV4 H1N1pdm09 -\nl\nike vaccine virus, which was subsequently updated.\nLAIV4 again a recommended option starting in 2018- 1 9 after discussion of\n–Combined U.S. individual level patient VE analysis,\n–Systematic review of post -2 009 US/non- US LAIV VE estimates,\n–MedImmune d ata suggesting better fitness of new H1N1pdm09 vaccine virus.\nLAIV4 use within CDC U.S. VE networks has been low since 2018 -1 9, precluding \nassessment of vaccine- specific VE.\nLAIV VE estimates have been published from non- U .S. observational studies. \n2\nVaccine Effectiveness, %\n* Report notes that 92% in 2 -6y age group received LAIV4; the remainder offered IIV4.362018- 19\n3654\n49536871\n4572\n646373\n-4Published Non- US VE \nEstimates\nAll influenza viral \ntypes/subtypes\n1. Stuurman et al  Vaccine \n2020;\n38:6455-6463\n2. Pebody, Vaccine 38 (2020) 489–4\n3. Stuurman et al  Vaccine 2021;\n39:3964-3973\n4. https://webarchive.nationalarchive\ns.gov.uk/ukgwa/20220401215804/\nhttps://www.gov.uk/government/s\ntatistics/annual -flu-reports\n5. https://www.gov.uk/government/s\ntatistics/annual -flu-\nreports/surveillance -of-influenza -\nand- other -seasonal -respiratory -\nviruses-in -winter -2021- to-2022\n6. Emborg ,  Euro Surveill\n2022;27:pii=2200278LAIV4 IIV4\nAll vaccines\nFIN    FinlandUK     United Kingdom\nDEN    Denmark\n0102030405060708090\nFIN (1)\nLAIV4\n2-6yFIN (1)\nIIV4\n6m-6yUK (2)\nLAIV4\n2-17yUK (2)\nall vaccines\n2-17yFIN (3)\nLAIV4\n2-6yFIN (3)\nIIV4\n6m-6yUK (4)\nLAIV4\n2-17yUK (5)\nLAIV4\n2-17yUK (5)\nall vaccines\n1-17yDEN (6)\nall\nvaccines*\n2-6y\nnon-hospDEN (6)\nall\nvaccines*\n2-6y\nhosp2019- 20 2021- 22\n4\nFor more information, contact CDC\n1-800- CDC- INFO (232 -4636)\nTTY:  1 -888- 232- 6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position o f the Centers for Disease Control and Prevention.\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation use. No rights are implied or extended for use in printing or \nany use by other CDC CIOs or any external audiences.", "summary": "National Center for Immunization & Respiratory Diseases Published Estimates of LAIV Effectiveness Lisa Grohskopf Advisory Committee on Immunization Practices February 22, 2023 Update on Published Estimates of LAIV4 Effectiveness: Background LAIV4 not recommended in the U.S. for 2016 -17 and 2017- 18, following  observation of poor effectiveness against H1N1pdm09 viruses. Subsequent studies suggested poor replicative fitness of the LAIV4 H1N1pdm09 - l ike vaccine virus, which was subsequently…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/influenza-05-Grohskopf-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 4}
{"title": "Pneumococcal 01 Poehling 508", "content": "Pneumococcal Vaccines \nKatherine A. Poehling, MD, MPH \nPneumococcal Vaccines Work Group Chair \nAdvisory Committee on Immunization Practices \nFebruary 22, 2023 \n   \n \n  \n  \n  \n   \n             \n    \n \n  \n \n     \n                 \n              \n          \n                 \n    \n          \n      \n             \n            \n           \n          \n                 \n     Pneumococcal Vaccines Work Group \nACIP Members \n• Katherine Poehling (Chair) \n• Sarah Long \nEx Officio Members • Jeffrey Kelman (CMS) \n• Lucia Lee (FDA) \n• Tina Mongeau (FDA) \n• Uzo Chukwuma (IHS) \n• Mamodikoe Makhene (NIH) \nCDC Lead \n• Miwako Kobayashi (NCIRD) Liaison Representatives and Consultants \n• Lynn Fisher (AAFP) \n• Mark Sawyer (AAP/COID) \n• Jason Goldman (ACP) \n• David Nace (AGS/AMDA) \n• Aleksandra Wierzbowski (NACI) \n• James McAuley (IDSA) \n• William Schaffner (NFID) \n• Virginia Caine (NMA) \n• Monica Farley (VAMC/Emory) \n• Keith Klugman (BMGF) \n• Arthur Reingold (UC Berkley) \n• Lorry Rubin (CCMC) \n• Richard Zimmerman (U. of Pittsburgh) \n   \n \n              \n                \n           \n                \n   \n               \n    \n          \n \n Pneumococcal Vaccines Work Group \nCDC Contributors \n• Adam Cohen (Respiratory Diseases Branch) \n• Ryan Gierke (Respiratory Diseases Branch) \n• Jennifer Farrar (Respiratory Diseases Branch) \n• Pedro Moro (Immunization Safety Office) \n• Liz Velazquez (Immunization Services Division) \n• Marc Fischer (Arctic Investigations Program) \n• Noele Nelson (Division of Bacterial Diseases) \n• Jessica MacNeil (ACIP Secretariat) \nGRADE/EtR consultants \n• Doug Campos-Outcalt \n• Rebecca Morgan \n     \n    \n    \n  \n  \n    \n  Pneumococcal vaccines currently recommended for \nuse in the United States \nRecommended for \nchildren Recommended for adults \nPneumococcal conjugate vaccines \nPCV13 \nPCV15 \nPCV20 \nPneumococcal polysaccharide vaccine PPSV23 Risk-based \nrecommendations If previously received PCV13 or PCV15 \n         \n  \n      \n    \n \n       All children under age 2 years have the same \npneumococcal vaccine recommendations \n• 3 primary series and a booster=“3+1” schedule \nPCV PCV PCV PCV 2months 4months 12–15 months 6months \nPrimary Series Booster \nEither PCV13 or PCV15 can be used for U.S. children. \n       \n         \n \n \n \n   \n  \n  \n   \n \n   \n Children with certain underlying conditions are recommended \nto receive PPSV23 in addition to the recommended PCV doses \nPPSV23 Recommended \nPCV doses Recommended \nPCV doses Healthy \nchildren \nCMC, CSF leak, \ncochlear \nimplant \n≥8 weeks \nRecommended \nPCV doses PPSV23 PPSV23 Immuno-\ncompromised \n≥8 weeks ≥5 years \nCMC aged 6–18 \nyears PPSV23 \n                 \n         \n           \n  Note: Excludes catch-up vaccination schedules. \nCMC=chronic medical conditions, including chronic heart disease, chronic lung disease, diabetes mellitus \nCSF=cerebrospinal fluid \nUse of 15-Valent Pneumococcal Conjugate Vaccine Among U.S. Children: Updated Recommendations of the Advisory Committee on Immunization \nPractices — United States, 2022 | MMWR (cdc.gov) \n        \n   \n  \n  \n  \n2022 2023 February 2023 \nPediatric PCV20 use approval \nanticipated Q2 2023 \nPediatric PCV15 use \nJune 2022 approved Approval of PCV20 use among Children Anticipated in 2023 \n               \n       U.S. FDA Accepts for Priority Review the Supplemental Biologics License Application for Pfizer’s 20-Valent Pneumococcal \nConjugate Vaccine in Infants and Children | Pfizer \n      \n        \n       \n       \n          \n         \n        \n Policy questions considered by the Work Group \n• Should PCV20 be recommended as an option for pneumococcal \nconjugate vaccination according to currently recommended dosing \nand schedules, for U.S. children aged <2 years ? \n• Should PCV20 without PPSV23 be recommended as an option for \npneumococcal vaccination for U.S. children aged 2–18 years with \nunderlying medical conditions that increase the risk of \npneumococcal disease? \n    \n   \n  \n     \n    \n       \n         \n \n         \n         \n        Today’s Pneumococcal Vaccines session outline \nIntroduction Dr. Katherine Poehling \n(ACIP , WG Chair) \nEpidemiology of pneumococcal disease among U.S. children Mr. Ryan Gierke (CDC/NCIRD) \nPediatric outpatient ARI visits and antibioticattributable to serotypes in higher valency PCVs use Ms. Laura King (U.C. Berkeley) \nPCV20 phase 2/3 study results among children Dr. Wendy Watson \n(Pfizer) \nPreliminary EtR for PCV20 use in U.S. children Dr. Miwako Kobayashi \n(CDC/NCIRD) \nWork Group considerations and next steps Dr. Miwako Kobayashi \n(CDC/NCIRD)", "summary": "Pneumococcal Vaccines  Katherine A. Poehling, MD, MPH  Pneumococcal Vaccines Work Group Chair  Advisory Committee on Immunization Practices  February 22, 2023                                                                                                                                                                                                                   Pneumococcal Vaccines Work Group  ACIP Members  • Katherine Poehling (Chair)  • Sarah Long  Ex Officio Members • Jeffrey Kelman…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/Pneumococcal-01-Poehling-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 9}
{"title": "Pneumococcal 02 Gierke 508", "content": "National Center for Immunization & Respiratory Diseases       \n     \n  \n    \n    Current Epidemiology of Pediatric Pneumococcal \nDisease, United States \nRyan Gierke, MPH \nAdvisory Committee on Immunization Practices \nFeb 22, 2023 \n1 \n     \n        \n \n Pneumococcal carriage is precursor to pneumococcal disease \nNoninvasive Disease \nInvasive Disease More frequent \nLess frequent \nBogaert, Lancet Infect Dis 2004;4:144-54 2 \n    \n        \n  \n        \n       \n    \n  \n  \n  \n      \n  Outline \n Invasive Pneumococcal Disease (IPD) in children \n• Impact of Pneumococcal Conjugate Vaccines (PCVs) on IPD incidence and \nserotype distribution \n• IPD incidence caused by serotypes in PCV15 and PCV20 \n• Changes in IPD incidence and serotype distribution post-COVID19 \n Acute Otitis Media (AOM) \n• Impact of PCV13 \n• Incidence Estimates \n Pneumonia in children • Impact of PCV13 on all-cause and pneumococcal pneumonia \n• Incidence Estimates \n3 \n\n       \n      \n   Impact of PCVs on Invasive Pneumococcal Disease \n(IPD) Incidence and Serotype Distribution among \nChildren in the U.S. \n4 \n     \n    \n  \n  \n           \n       \n         \n         Methods \n Active Bacterial Core surveillance (ABCs): \n Active laboratory and population-based \nsurveillance, 10 sites \n Pneumococcus isolation from sterile site \n Isolates serotyped by whole genome sequencing, Quellung, or PCR at reference labs and grouped for analysis by vaccine type \n US Census Bureau race-bridged post-census population estimates used as denominators \n Overall and serotype-specific IPD incidence rates (cases per 100,000 people) \n5 \n               \n  \n  \n  \n Incidence rates of invasive pneumococcal disease (IPD) among children < 5 \nyears old, 1998–2019 \n0 10 20 30 40 50 60 70 80 90 100 Cases per 100,000 persons All IPD PCV13+6C Non-PCV13 PCV7 introduction \nPCV13 introduction \nchildren * \n1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 \nYear \n                *Serotype 6C was grouped with PCV13 serotypes due to cross protection from 6A antigen in the vaccine 6 \n   \n             \n   \n Incidence rates of invasive pneumococcal disease (IPD) among children < 5 \nyears old, 2007 – 2021 \n25 \n20 15 \n10 \n5 \n0 \n2007 2008 2009 2010 2011 2012 2013 2014 \nYear 2015 2016 2017 2018 2019 2020 2021 Cases per 100,000 ALL IPD \nPCV13 + 6C \nNon-PCV13 PCV13: children \nCOVID-19 * \n                7 \n*Serotype 6C was grouped with PCV13 serotypes due to cross protection from 6A antigen in the vaccine \nIncidence rates of IPD among children < 5 years old, 2011 – 2021, \nby PCV13+6C*serotypes \n2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 \nYear 0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0 Cases per 100,000 population 001 005 \nPCV7 (except 19F) 19F \n06C 003 \n07F 19A % of PCV13+6C serotypes \n2018-2019 2020-2021 \n003 46% 18% \n19F 32% 60% \n19A 14% 18% \n06C 4% 0% \nCOVID-19                     \n   \n                *Serotype 6C was grouped with PCV13 serotypes due to cross protection from 6A antigen in the vaccine 8 \n       \n    Current Pediatric Pneumococcal Disease Incidence Caused by \nSerotypes in PCV15 and PCV20 \n9 \n       \n  \n         \n    \n      \n         \n        Serotypes contained in current and new pneumococcal \nvaccines \n1 3 4 5 6A 6B 7 F 9V 14 18 \nC 19 \nA 19 F 23 F 22 F 33 F 8 10 A 11 A 12 F 15 B 2 9N 17 \nF 20 \nPCV13 \nPCV15 PCV20 PPSV23 \nFor analysis purposes: \n• PCV13+6C : includes serotype 6C with PCV13 types due to cross \nprotection from 6A antigen \n• PCV15 non-PCV13 : includes serotypes 22F and 33F \n• PCV20 non-PCV15 : includes serotypes 8, 10A, 11A, 12F, and 15B \n• PPSV23 non-PCV20 : includes serotypes 2, 9N, 17F, and 20 \n10 \nIncidence rates of IPD among children <5 years old, \n2011 – 2021, by vaccine type \n14 \n12 10 \n8 6 4 2 \n0 \n2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 PCV13+6C PCV15/ non-PCV13 PCV20/ non-PCV15 \nPPSV23/ non-PCV20 Non-Vaccine Type \nCOVID-19 Proportion of IPD \n2018-2019 2020-2021 \nNon-Vaccine Type 46% 52% \nPPSV23/ non-PCV20 1% 4% \nPCV20/ non-PCV15 15% 13% \nPCV15/ non-PCV13 17% 15% \nPCV13+6C 21% 16%        \n         \n    \n \n \n \n \nYear Cases per 100,000 population \n    \n       \n       PCV15 non-PCV13 serotypes: 22F, 33F P\nCV20 non-PCV15 serotypes: 8, 10A, 11A, 12F, 15B \nPPSV23 non-PCV20 serotype: 2, 9N, 17F ,20 11 \n     \n    \n \n \n \n           \n    Incidence rates of IPD among children 5 -18 years old, \n2011 – 2021, by vaccine type Cases per 100,000 population \n0.0 0.5 1.0 1.5 2.0 2.5 \n2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 PCV13+6C PCV15/ non-PCV13 PCV20/ non-PCV15 \nPPSV23/ non-PCV20 Non-Vaccine Type % of IPD \n2018-2019 2020-2021 \nNon-Vaccine Type 32% 36% \nPPSV23/ non-PCV20 5% 5% \nPCV20/ non-PCV15 13% 16% \nPCV15/ non-PCV13 16% 9% \nPCV13+6C 34% 34% \nCOVID-19 \n    \n       \n       Year \nPCV15 non-PCV13 serotypes: 22F, 33F PCV20 non-PCV15 serotypes: 8, 10A, 11A, 12F, 15B PPSV23 non-PCV20 serotype: 2, 9N, 17F ,20 12 \n                       \n \n                         \n \n      \n  \n     \n \n \n IPD incidence among children with \nimmunocompromising conditions, 2015-2019* \nChildren < 5 years Children 5-17 years \n10000 10000 Rate Ratio=231 \nRate Ratio=29 \n1 Cases Per 100,000 persons \n(Log scale) 1000 \nCases Per 100,000 persons \n(Log scale) 1000 \nRate Ratio=71 \n100 100 \n10 \nSickle Cell Diseaseˆ 10 \n1 \nHematologic Malignancy Sickle Cell Diseaseˆ \nCondition No condition Condition No condition \n                  \n               CDC \nunpublished data, IPD cases identified from ABCs \n*Hematologic Malignancy Data only available from 2015-2018 for children age <5 years \nˆ IPD rates for those with and without sickle cell disease are among African American children 13 \nAcute  Otitis  Media  (AOM) i n Children \n14 \n       \n       \n      \n      \n     \n        \n    \n    \n     \n   PCV13 impact on acute otitis media in children \n AOM is a major cause of childhood morbidity1,2,3 \n• Pneuococcus is a common bacterial cause of AOM \n• S. pneumoniae accounted for an estimated 24%4 \n AOM incidence decreased after PCV13 introduction \n• 11%-14% decrease, depending on age group and study years1,2 \n1 Tong et al. BMC 2018 \n2 King et al. ASHE 2021 \n3Casey et al Clin Pediatr 2014; \n4Kaur et al. EJCMID 2022 15 \n\n     \n \n \n \n       \n   \n    Incidence of acute otitis media among children \nAOM visits per 100,000 Person Years \n20141 2014-20182 2016-20183 \n<1 43,180 -- --\n1 year 47,860 -- --\n<2 years -- 76,880 49,050 \n2-4 years 29,980 41,030 31,970 \n5-17 years 9,060 9,180 5,680 \nAOM incidence highest \namong children age <5 years \n1  Ton  g et  al.  BMC 2018 \n2  Hu  et  al.  BMC 2022 \n3Unpublishe  d analysi  s courtesy  o f Laura  King,  U C Berkeley 16 \n\n  Pneumonia in Children \n17 \n       \n          \n   \n    \n           \n         \n   \n   \n   Evidence of PCV13 impact on pneumonia in children \n Reduction in incidence of all-cause and pneumococcal pneumonia among in \nchildren following PCV13 introduction1,2,3 \n• 17-35% reduction in all cause-pneumonia1 \n• 40% and 51% reduction in inpatient pneumococcal pneumonia among ages <1 \nand 5-17 years, respectively; no reductions in ages 2-4 years2 \n1Tong et al. BMC 2018 \n2 Simonsen et al. Lancet 2014 \n18 3King et al. ASHE 2021 \n\n  \n     \n        \n       \n    \n Pneumonia incidence among children \nAge (years) All-cause pneumonia (frequency per \n100,000 person years)1 , 2014 All-cause inpatient pneumonia (cases \nper 100,000 population)2 , 2018–19 \n< 1 2,250 680 \n1 3,990 480 \n2–4 3,390 290 \n5–17 1,280 87 \n1 Tong et al. BMC 2018 \n2 National Inpatient Sample, 2018-2019 \n18 \n\n           \n   \n          \n   \n          \n    \n    Conclusions \n• Use of PCVs (PCV7, PCV13) significantly decreased the incidence of pneumococcal \ndisease in U.S. children \n• Risk of disease remains higher in children with immunocompromising conditions compared to children without \n• In 2018–2019, the proportion of IPD caused by vaccine serotypes was: \n• PCV20, non-PCV13: ~30% of IPD \n• PCV15, non-PCV13: ~15% of IPD \n20 \n\n    \n \n      \n                  \n         Questions \nFor more information, contact CDC \n1-800-CDC-INFO (232-4636) TTY: 1-888-232-6348 www.cdc.gov \nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.", "summary": "National Center for Immunization & Respiratory Diseases                          Current Epidemiology of Pediatric Pneumococcal  Disease, United States  Ryan Gierke, MPH  Advisory Committee on Immunization Practices  Feb 22, 2023  1                    Pneumococcal carriage is precursor to pneumococcal disease  Noninvasive Disease  Invasive Disease More frequent  Less frequent  Bogaert, Lancet Infect Dis 2004;4:144-54 2                                                           Outline  …", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/Pneumococcal-02-Gierke-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 21}
{"title": "Pneumococcal 03 King 508", "content": "Laur  a King,  MPH \nAdvisor  y Committ  ee o  n Immunizatio  n Practices \nFebruar  y 22  , 2023 PP PPeeeeddddiiiiaa aattttrrrriiiiccc    c oo oouu uuttttpp ppaaaattttii iiee eenn nnttt  t   AAAARR RRIII  I   vv vvii iissssii iitttts ss  s   aa aannnnddd  d   aa aannnnttttii iibbbbii iioo oott ttiiiic cc  c   uu uusssseee  e   \naaaatt tttt ttrrrriiiibb bbuu uuttttaa aabb bblllleee    e tt tto oo  o   ss sseeeerrrroooott ttyyyypp ppeeees ss  s   ii iinnn  n   hhhhii iigg gghhhhee eerrr  r   vvvvaaaallllee eenn nncc ccy yy    y PP PPCC CCVV VVssss \n          \n          \n        \n      \n \n Disclosures \n• Laura King has received consulting fees from Merck for unrelated \nwork. \n• Joseph Lewnard has received consulting fees and grants from Pfizer, Merck, and VaxCyte for related and unrelated work. \n• All other authors report no conflicts. \n2 \n   \n       \n        \n        \n   \n \n  \n Overview \n• Background and study objective \n• Pediatric outpatient visit and antibiotic prescription incidence \n• Acute otitis media vaccine serotype attributable proportion and incidence \n• Sinusitis and pneumonia vaccine serotype attributable proportion and \nincidence \n• Summary and conclusions \n3 \n     \n           \n   \n        \n          \n          \n    \n          \n          \n \n Outpatient respiratory infections: a sizeable \nburden \n• ~1,200 acute respiratory infection (ARI) visits per 1,000 children in a \ncommercially-insured population in 20181 \n• ~250 ARI-associated antibiotic prescriptions per 1,000 children issued from doctor’s offices and emergency departments in the US annually (2014-15)\n2 \n• Limited knowledge of the proportion of ARI visits and antibiotic prescriptions attributable to Streptococcus pneumoniae \n1. King LM, et al. Antimicrob Steward Healthc Epidemiol . 2021;1(1):1-8. doi: 10.1017/ash.2021.230. \n2. Hersh AL, et al. Clin Infect Dis . 2021;72(1):133-137. doi: 10.1093/cid/ciaa667. 4 \n      \n \n        \n         Reductions in antibiotic use concurrent with \nPCV uptake \nUS outpatient oral antibiotic prescriptions per 1,000 persons, 2011-2016 \nKing et al., Clin Infect Dis . 2020; 70(3):370-377). doi: 10.1093/cid/ciz225. 5 \n \n          \n  \n        Study objective \nVisits and antibiotic prescriptions attributable to additional serotypes in \nhigher-valency PCVs = \nIncidence  o f all -caus  e \npediatric  outpatient visi  ts \nand  antibiotic  prescriptions\nfor  AOM  , pneumonia,  and  \nsinusitis \n Proportio  n of outpatient  \ndiseas  e caused  by  S.  \npneumoniae PCV15 -13  and  \nPCV20 -13  serotypes* \n*PCV15-13/PCV20-13 serotypes: serotypes in PCV15/PCV20 not in PCV13 6 \nVisits and antibiotic prescriptions attributable to additional serotypes in \nhigher-valency PCVs =\nIncidence  o f all -caus  e \npediatric  outpatient visi  ts \nand  antibiotic  prescription  s \nfor  AOM  , pneumonia,  and  \nsinusitis Proportio  n of outpatient  \ndiseas  e caused  by  S.  \npneumoniae PCV15 -13  and  \nPCV20 -13  serotypes \n7 \n   \n           \n     All-cause incidence estimation methods \n \nTotal incidence = incidence in physician offices and emergency departments + \nincidence in all other outpatient settings \n8 Setting  Data  source  for  number  of  visits \n and antibiotics  Data  source  for -  person years \n at risk \n Physician offices   NAMCS 2016, 2018    US Census 2016, 2018 \n Emergency departments   NHAMCS 2016, 2018    US Census 2016, 2018 \n  Alternative outpatient \nsettings   MarketScan Commercial and  \n  Medicaid Databases 2016-2018   MarketScan Commercial and  \n  Medicaid Databases 2016-2018\n     \n     \nCondition  Outpatient  visits  per  1000 \n person-years  (95% CI)  Antibiotic  prescriptions  per \n  1000 person-years  (95% CI) \nAOM   146 (116, 180)   124 (103, 149) \nSinusitis    40 (27, 58)   39 (24, 60) \nPneumonia   21 (14, 30)   17 (13, 21) \nTotal   208 (168, 254)   181 (148, 218) All-cause visit and antibiotic prescription \nincidence in children by condition \n9 \n           \n  \nIncidence  of pediatric  \noutpatient  visits  and \nantibiotic  prescriptions  fo\nAOM,  pneumonia,  and \nsinusitisrVisits and antibiotic prescriptions attributable to additional serotypes in \nhigher-valency PCVs = \nProportio  n of outpatient  \ndiseas  e caused  by  S.  \npneumoniae PCV15 -13  and\nPCV20 -13  serotypes \n \n10 \n      \n     \n    \n         \n         \n \n Challenges in estimating the proportion of \noutpatient disease caused by S. pneumoniae \n• Children frequently colonized with pneumococcus \n• Samples not regularly obtained from infection site in outpatient \ndisease \n• Few studies conducted for non-AOM ARIs in pediatric outpatients \n11 \n                    \n                    cc cii idd dee enn ncc cee eoo off foo ouu utt tpp paa att tii iee enn ntt tAA AOO OMM M PP Prr roo opp poo orr rtt tii ioo onn naa ann ndd d\ncc caa auu uss see edd dbb byy yPP PCC CVV V11 155 5-- -11 133 3aa ann ndd dPP PCC CVV V22 200 0-- -11 133 3ss see err roo ott tyy ypp pee ess siinn Proportion and incidence of outpatient AOM \ncaused by PCV15-13 and PCV20-13 serotypes in \n12 \n      \n    \n        \n      \n       \n     \n        \n         AA AOO OMM MThree approaches to estimating PCV15-13 and \nPCV20-13 attributable proportions in AOM \n1. Vaccine probe: use vaccine effectiveness against disease associated \nwith all etiologies to estimate attributable proportion \n2. Pneumococcal prevalence and serotype distribution from middle ear fluid in children with AOM \n3. Differential nasopharyngeal (NP) carriage between sick and healthy children and NP carriage serotype distribution in children with AOM \n13 \n    \n \n    \n    \n       \n        \n        AA AOO OMM MAOM pneumococcal and vaccine serotype \nattributable percents \nAOM attributable percent (95% CI) \nMethod All pneumococcal \nserotypes PCV15-13 serotypes PCV20-13 serotypes \nVaccine probe 16.7 (4.3, 41.9) 0.9 (0.2, 2.3) 4.5 (1.1, 11.5) \nMiddle ear fluid 22.3 (17.1, 27.5) 1.0 (0.7, 1.4) 5.1 (3.9, 6.4) \nDifferential NP \ncarriage 14.0 (2.0, 26.0) 0.7 (0.1, 1.5) 3.7 (0.5, 7.1) \n14 \n    \n     \n          \n    \n           \n            \n         \n        vv vii iss sii itt tss s Estimated pediatric outpatient visits for AOM \nattributable to PCV15-13 and PCV20-13 serotypes \nIncidence per 1000 person-years (95% CI) Annual number in thousands* (95% CI) \nMethod PCV15-13 serotypes PCV20-13 serotypes PCV15-13 serotypes PCV20-13 serotypes \nVaccine probe 1.3 (0.3, 3.5) 6.5 (1.6, 17.1) 92 (23, 257) 477 (121, 1,251) \nMiddle ear fluid 1.5 (1.0, 2.2) 7.4 (5.2, 10.2) 109 (72, 161) 543 (381, 747) \nDifferential NP \ncarriage 1.0 (0.1, 2.2) 5.4 (0.8, 10.7) 76 (11, 165) 397 (56, 787) \n*Estimated using 2018 census estimate for children <18 years 15 \n       \n     \n  \n          \n    \n         \n            \n          \n        aa ann ntt tii ibb bii ioo ott tii icc c\npp prr ree ess scc crr rii ipp ptt tii ioo onn nss sEstimated pediatric outpatient antibiotic \nprescriptions for AOM attributable to PCV15-13 and PCV20-13 serotypes \nIncidence per 1000 person-years (95% CI) Annual number in thousands* (95% CI) \nMethod PCV15-13 serotypes PCV20-13 serotypes PCV15-13 serotypes PCV20-13 serotypes \nVaccine probe 1.1 (0.3, 3.0) 5.6 (1.4, 14.5) 79 (19, 217) 408 (104, 1,065) \nMiddle ear fluid 1.3 (0.9, 1.8) 6.3 (4.5, 8.5) 93 (63, 135) 464 (333, 626) \nDifferential NP \ncarriage 0.9 (0.1, 1.9) 4.6 (0.7, 9.1) 65 (9, 139) 340 (48, 666) \n*Estimated using 2018 census estimate for children <18 years 16 \n                    \n                        PP Prr roo opp poo orr rtt tii ioo onn naa ann ndd dii inn ncc cii idd dee enn ncc cee eoo off foo ouu utt tpp paa att tii iee enn ntt tpp pnn nee euu umm moo onn nii iaa a\naa ann ndd dss sii inn nuu uss sii itt tii iss scc caa auu uss see edd dbb byy yPP PCC CVV V11 155 5-- -11 133 3aa ann ndd dPP PCC CVV V22 200 0-- -11 133 3\nss see err roo ott tyy ypp pee ess sProportion and incidence of outpatient pneumonia \nand sinusitis caused by PCV15-13 and PCV20-13 \nserotypes \n17 \n      \n        \n        \n          \n      pp pnn nee euu umm moo onn nii iaa a\nss sii inn nuu uss sii itt tii iss sTwo approaches to estimating PCV15-13 and \nPCV20-13 attributable proportions in pneumonia \nand sinusitis \n1. Vaccine probe: use vaccine effectiveness to estimate attributable \nproportion \n2. Differential NP carriage between sick and healthy children and NP carriage serotype distribution in children with AOM \n18 \n   \n  \n    \nMethod   All pneumococcal \nserotypes  PCV15-13 serotypes  PCV20-13 serotypes \n Vaccine probe   18.2 (12.5, 27.3)   0.9 (0.5, 1.5)   4.4 (2.9, 6.7) \n Differential NP carriage   11.8 (1.0, 22.7)   0.6 (0.0, 1.2)   2.8 (0.2, 5.5) PP Pnn nee euu umm moo onn nii iaa a Pneumonia pneumococcal and vaccine \nserotype attributable percents \nPneumonia attributable percent (95% CI) \n19 \n   \n    \n   \n    \n     \n \n    \n          \n         \n          \n         \n        pp pnn nee euu umm moo onn nii iaa a Estimated pneumonia pediatric outpatient visits \nand antibiotic prescriptions attributable to PCV15 -\n13 and PCV20-13 serotypes \nIncidence per 1000 person-years \n(95% CI) Annual number in thousands* \n(95% CI) \nOutcome Method PCV15-13 \nserotypes PCV20-13 \nserotypes PCV15-13 \nserotypes PCV20-13 \nserotypes \nVaccine probe 0.2 (0.1, 0.4) 0.9 (0.5, 1.6) 14 (7, 26) 68 (39, 118) \nOutpatient visits \nDifferential NP \ncarriage 0.1 (0.0, 0.3) 0.6 (0.1, 1.3) 9 (1, 21) 43 (4, 95) \nAntibiotic prescriptions Vaccine probe \nDifferential NP \ncarriage 0.1 (0.1, 0.3) \n0.1 (0.0, 0.2) 0.7 (0.5, 1.2) 0.5 (0.0, 1.0) 11 (6, 19) \n7 (1, 15) 53 (34, 86) \n34 (3, 70) \n*Estimated using 2018 census estimate for children <18 years 20 \n    \n    \n       \n       SSSSiinininnuuuussssiiiittttiiiis ss s pneumococcal  an d vaccine  serotype  \nattributable  percents \nSinusitis attributable percent (95% CI) \nMethod All pneumococcal \nserotypes PCV15-13 serotypes PCV20-13 serotypes \nVaccine probe 30.6 (21.0, 45.8) 1.5 (0.9, 2.5) 7.3 (4.9, 11.2) \nDifferential NP carriage 11.8 (1.0, 22.7) 0.6 (0.0, 1.2) 2.8 (0.2, 5.5) \n21 \n    \n    \n  \n    \n     \n \n    \n          \n         \n          \n         \n        ss sii inn nuu uss sii itt tii iss s Estimated sinusitis pediatric outpatient visits and \nantibiotic prescriptions attributable to PCV15-13 \nand PCV20-13 serotypes \nIncidence per 1000 person-years Annual number in thousands* \n(95% CI) (95% CI) \nPCV15-13 PCV20-13 PCV15-13 PCV20-13 \nOutcome Method serotypes serotypes serotypes serotypes \nVaccine probe 0.6 (0.3, 1.2) 2.9 (1.7, 5.2) 44 (23, 85) 216 (122, 381) \nOutpatient visits \nDifferential NP 0.2 (0.0, 0.5) 1.1 (0.1, 2.5) 17 (1, 40) 82 (7, 180) carriage \nVaccine probe 0.6 (0.3, 1.2) 2.9 (1.5, 5.2) 43 (21, 85) 209 (112, 384) \nAntibiotic \nprescriptions Differential NP 0.2 (0.0, 0.5) 1.1 (0.1, 2.5) 16 (1, 39) 79 (7, 181) carriage \n22 \n*Estimated using 2018 census estimate for children <18 years \n        SS Suu umm mmm maa arr ryy yaa ann ndd dcc coo onn ncc cll luu uss sii ioo onn nss s Summary and conclusions \n23 \n     \n    \n  \n \n  \n     \n  \n    \n    \n              Point estimate ranges: attributable percent, \nnumber visits, number antibiotic prescriptions \nPCV15-13 serotypes PCV20-13 serotypes \nCondition Attributable \npercent of \noutpatient \ndisease Annual no., in thousands \nOutpatient Antibiotic \nvisits prescriptions Attributable \npercent of \noutpatient \ndisease Annual no., in thousands \nOutpatient Antibiotic \nvisits prescriptions \nAOM 0.7–1.0 76–109 65–93 3.7–5.1 397–543 340–464 \nPneumonia 0.6–0.9 9–14 7–11 2.8–4.4 43–68 34-53 \nSinusitis 0.6–1.5 17–44 16–43 2.8–7.3 82–216 79–209 \nTotal* 1.9–3.4 103–168 90–148 9.4–16.8 527–831 458–731 \n*Individual condition ranges may not sum to total ranges due to simulation methods and rounding 24 \n \n      \n      \n         \n   \n    \n      \n  \n Study limitations \n• Pneumococcal attributable percent, serotype distribution, and \nvaccine effectiveness estimates based on published data \n• Limited data for attributable proportion and serotype distribution in sinusitis and pneumonia \n• All-cause incidence data from 2016-2018 \n• Assumed healthcare utilization constant across serotypes \n25 \n        \n       \n         \n  \n       \n       \n         \n         \n     \n  \n Conclusions \n• Additional serotypes included in higher-valency PCVs account for \n~100–830 thousand outpatient visits and ~90–730 thousand antibiotic prescriptions for AOM, pneumonia, and sinusitis among US children annually. \n• PCV15-13 serotypes: 103–168K visits and 90–148K antibiotic prescriptions \n• PCV20-13 serotypes: 527–831K visits and 458–731K antibiotic prescriptions \n• The estimated incidence of pediatric outpatient visits and antibiotic prescriptions attributable to PCV20-13 serotypes is 4 – 5 times the \nincidence attributable to PCV15-13 serotypes. \n26 \n \n \n  \n  \n   \n   \n  \n       \n   \n   \n \n \n   \n Project team \nUC Berkeley \n• Laura King, MPH \n• Joe Lewnard, PhD \nCDC Respiratory Diseases Branch \n• Miwako Kobayashi, MD, MPH \n• Kristin Andrejko, PhD \n• Adam Cohen, MD, MPH CDC Office of Antibiotic \nStewardship \n• Sarah Kabbani, MD, MS \n• Lauri Hicks, DO \n27", "summary": "Laur  a King,  MPH  Advisor  y Committ  ee o  n Immunizatio  n Practices  Februar  y 22  , 2023 PP PPeeeeddddiiiiaa aattttrrrriiiiccc    c oo oouu uuttttpp ppaaaattttii iiee eenn nnttt  t   AAAARR RRIII  I   vv vvii iissssii iitttts ss  s   aa aannnnddd  d   aa aannnnttttii iibbbbii iioo oott ttiiiic cc  c   uu uusssseee  e    aaaatt tttt ttrrrriiiibb bbuu uuttttaa aabb bblllleee    e tt tto oo  o   ss sseeeerrrroooott ttyyyypp ppeeees ss  s   ii iinnn  n   hhhhii iigg gghhhhee eerrr  r  …", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/Pneumococcal-03-King-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 27}
{"title": "Pneumococcal 04 Watson 508", "content": "20-valent Pneumococcal \nConjugate Vaccine \n(PCV20) Phase 3 \nin Pediatrics \nWendy Watson, MD \nGlobal Clinical Program Lead \nACIP February 22, 2023 \n1 \nPCV20 is Built on the Established Platforms of PCV7 and PCV13 \n• PCV20 builds on the 20 -year legacy of PCVs and contains PCV13 components + conjugates for 7 additional PCV20 \nComposition serotypes to broaden disease coverage for pneumococcal disease in children \n• The 7 additional conjugates were modelled on the PCV13 Pfizer platform \n• Licensure based on satisfactory safety and immunogenicity compared to PCV13 \n• Totality of data to support comparability per regulatory agreement Licensure and • Seeking same indications as PCV13 Indications \n• PCV20 in the pediatric program is the same vaccine currently approved, recommended, and administered in \nadults \nPCV13 PCV20 \nPCV7 \n4 6B 9V 14 18C 19F 23F 1 3 5 6A 7F 19A 8 10A 11A 12F 15B 22F 33F \n        \n \n     \n    \n  \n        \nCRM197 \nPCV7 \nImmunogenicity  & Safety  \nClinical Efficacy \nReal -World Effectiveness \nReal -World Impact \n2 PCV13 \nImmunogenicity  & Safety \nEfficacy from immunobridging \nReal -World Effectiveness \nReal -World Impact \nData available after vaccine implementation PCV20 \nImmunogenicity & Safety \nEfficacy from Immunobridging \nReal -World Effectiveness \nReal -World Impact \nPhase 2Senders \n et al. 2021 2, 4, 6 and \n 12 months \n of age 460\nParticipants     Demonstrate safety, tolerability, and immunogenicity of PCV20 \n  •Concomitant administration with Pediarix\n •United States\nPivotal Infant\nStudy 2, 4, 6 and \n 12–15 months \nof age 1997\nParticipants  Demonstrate noninferiority of immune response of PCV20 vs PCV13 \n  •Concomitant administration with Pediarix , Hiberix , M-M-R II, Varivax\n  •United States, Puerto RicoPhase 3 Pediatric \nSingle Dose \nStudy  Single dose \n (15 months – \n<18 years \nof age) 831 \nParticipants       Characterize safety and immunogenicity in children 15 months to\n17 years of age \n •United States\n Safety \nStudy  2, 4, 6 and \n 12–15 months \nof age 1511\nParticipants   Further characterize safety profile of PCV20 \n•Concomitant standard vaccines allowed\n    •United States, Puerto Rico, Canada, Chile, Argentina, European UnionPCV20 Clinical Development Program \n SAFETY \nIMMUNOGENICITY \n3 \n \n        \n   \n  \n   \n  \n  \n   \n  \n  \n  \n  \n     \n    \n  \n  \n           \n     \n  \n   \n  \n  \n   \n  \n  \n  \n  \n  PCV20\nN*=1001PCV13\nN*=987\nSex n†(%) n†(%)\nMale 518 (51.7) 505 (51.2)\nRace\nWhite 754 (75.3) 742 (75.2)\nBlack or African\nAmerican110 (11.0) 108 (10.9)\nAsian 16 (1.6) 16 (1.6)\nAmerican Indian or \nAlaska Native4 (0.4) 3 (0.3)\nNative Hawaiian or \nother Pacific \nIslander2 (0.2) 2 (0.2)\nMultiracial 68 (6.8) 73 (7.4)\nEthnicity\nHispanic/Latino 312 (31.2) 293 (29.7)\nNon Hispanic/\nnonLatino661 (66.0) 659 (66.8)-\n-\nPivotal Infant  Study \nStudy Design of Phase 3 Pivotal Study in Infants \nMulticenter, Randomized, Double -blind Study in the Similar Demographics of PCV20 \nUS/Puerto Rico Study in Infants (92 sites, n=1997) and PCV13 Groups \n2 4 6 7 12-15 13- 16 18- 21 Age months months months  months  months months months PCV20 PCV13\nN*=1001 N*=987 \nSex n† (%) n† (%)PCV20 Group \nMale 518 (51.7) 505 (51.2) \nRace \nWhite 754 (75.3) 742 (75.2)+ + + + PCV20 PCV20\n PCV20 PCV20 \nPediarix, Pediarix, Pediarix, MMR and \nHib Hib Hib Varicella \nControl Group \n+ + + + PCV13 PCV13 PCV13 PCV13 \nBlack or African \nAmerican 110 (11.0) 108 (10.9) \nAsian 16 (1.6) 16 (1.6) \nAmerican Indian or \nAlaska Native 4 (0.4) 3 (0.3) \nNative Hawaiian or \nother Pacific 2 (0.2) 2 (0.2) \nIslander \nMultiracial 68 (6.8) 73 (7.4) \nEthnicity \nHispanic/Latino 312 (31.2) 293 (29.7) \nNon-Hispanic/ \nnon-Latino 661 (66.0) 659 (66.8) Pediarix, \nHib Pediarix, \nHib Pediarix, \nHib MMR and \nVaricella \nBlood draws Safety follow -up call • Concomitant Influen\nany time during trial za and rotavirus vaccines permitted at \n*N=number of participants in the specified age cohort. This value is the denominator for the percentage calculations. \n†n=number of participants with the specified characteristic. \n4 \n Primary \nObjectives \n              \n                    \n    \n      \n    \n  \n   \n \n  \n     \n   \n  \n  \n \n    \n   \n     \n      \n   \n  \n  \n Key \nSecondary \nObjective  Pre-specified Immunogenicity  Analyses \nImportance of Multiple Immunologic Assessments to Infer Effectiveness Pivotal Infant Study  \nCo-primary :  Noninferiority  of  IgG GMCs  after \ntoddler dose Noninferiority  of  IgG GMC  after infant  series Co-primary  Noninferiority  of  % of  participants  with \nIgG above predefined levels after infant series \nCirculating IgG Antibody Functional Response Memory Response \n• % above prespecified IgG level after \ntoddler dose • OPA GMTs after infant series and \ntoddler dose • Geometric fold -rises (GMFR) of IgG \nfrom after infant series to after the \n• IgG GMCs and % above prespecified \nIgG for the 7 additional serotypes \nrelative to the PCV13 group • \n• % with OPA titers ≥ LLOQ after infant \nseries and toddler dose \nOPA titer RCDC after infant series and • toddler dose \nGMFR of IgG from before to after the \ntoddler dose \n• IgG Reverse Cumulative Distribution \nCurve ( RCDC ) after infant series and \ntoddler dose toddler dose • \n• GMFR of OPA from after infant series to \nafter the toddler dose \n% with ≤ 4-fold rise in OPA titers from \nbefore to after the toddler dose Additional Data \n• Concomitant Vaccine Antigen GMCs \nand GMRs \n• Comparison of % With Prespecified \nAntibody Levels for Concomitant \nVaccine Antigens \n• Explore cross protection to 6C and 15C \nNI for GMC ratio (GMR) = the lower bound of 2 -sided 95% CI for GMR (PCV20/PCV13) >0.5. \nNI for difference in percentages of participants = the lower bound of 2 -sided 95% CI for percent difference (PCV20 -PCV13) > -10%. \n5 \n \n  \n \n \n \n \n \n   \n            \n         Pivotal Infant  Study Co-Primary  Objective \nPost Dose 3 : Percentage with Predefined IgG Concentrations \n14 Serotypes Met Noninferiority (Difference in %) \nSerotype \nPCV13 PCV20 \n(%) PCV13 \n(%) Difference (% ) \n(95% CI) \n1 79.8 88.4 -8.6 (-12.1, -5.1) \n3 52.1 67.6 -15.5 ( -20.1, -10.8) \n4 79.7 88.2 -8.4 (-12.0, -4.9) \n5 82.5 86.8 -4.3 (-7.8, -0.8) \n6A 93.5 95.9 -2.4 (-4.6, -0.2) \n6B 88.3 92.4 -4.1 (-7.0, -1.2) \n7F 96.6 97.6 -1.0 (-2.7, 0.7) \n9V 81.9 89.8 -7.9 (-11.3, -4.6) \n14 93.4 94.1 -0.8 (-3.1, 1.6) \n18C 92.6 93.1 -0.6 (-3.1, 1.9) \n19A 97.1 98.1 -1.0 (-2.6, 0.5) \n19F 96.9 96.6 0.2 (-1.5, 2.0) \n23F 77.9 85.5* -7.6 (-11.4, -3.9) \n7 Addition al \n8 96.8 85.5 11.2 (8.6, 14.0) \n10A 82.2 85.5 -3.3 (-6.9, 0.3) \n11A 92.7 85.5 7.1 (4.2, 10.2) \n12F 67.5 85.5 -18.1 ( -22.1, -14.0) \n15B 98.2 85.5 12.7 (10.2, 15.4) \n22F 98.3 85.5 12.8 (10.3, 15.5) \n33F 86.7 85.5 1.1 (-2.2, 4.5) \n-30 -20 -10 0 10 20 30 \nDifference in Percentage (PCV20 –PCV13) \n*The 7 additional serotypes are compared to the percentage for serotype 23F after Dose 3 (lowest in PCV13 group, excluding serotype 3). \nPredefined IgG concentration – ≥0.35 µg/mL for all serotypes except ≥ 0.23 µg/mL, ≥0.10 µg/mL and ≥ 0.12 µg/mL for serotypes 5, 6B and 19A respectively. \n6 \n \n \n \n \n \n \n        Pivotal Infant Study Key Secondary   Objective  \nPost Dose 3 : IgG Concentration and Geometric Mean Ratio \nAll 20 Vaccine Serotypes Met Noninferiority \nSerotype \nPCV13 PCV20 \nGMC PCV13 \nGMC GMR \n(95% CI) \n1 0.74 1.14 0.65 (0.59, 0.72) \n3 0.36 0.51 0.70 (0.64, 0.76) \n4 0.75 1.08 0.70 (0.63, 0.78) \n5 0.66 0.96 0.69 (0.61, 0.77) \n6A 1.95 2.69 0.72 (0.65, 0.81) \n6B 0.61 1.02 0.60 (0.51, 0.70) \n7F 1.71 2.29 0.75 (0.69, 0.81) \n9V 0.87 1.21 0.72 (0.65, 0.80) \n14 2.16 2.72 0.79 (0.71, 0.89) \n18C 1.31 1.71 0.77 (0.70, 0.84) \n19A 0.72 0.91* 0.79 (0.72, 0.86) \n19F 1.59 2.00 0.79 (0.73, 0.86) \n23F 0.82 1.25 0.66 (0.58, 0.75) \n7 Additional \n8 1.80 0.91 1.98 (1.81, 2.16) \n10A 1.21 0.91 1.32 (1.18, 1.49) \n11A 1.39 0.91 1.52 (1.39, 1.67) \n12F 0.55 0.91 0.60 (0.54, 0.67) \n15B 4.40 0.91 4.82 (4.39, 5.30) \n22F 3.71 0.91 4.06 (3.68, 4.48) \n33F 1.49 0.91 1.64 (1.46, 1.83) \n0.25 0.5 1 2 4 8 \nGMR \n* The 7 additional serotypes are compared to the GMC after Dose 3 for serotype 19A (lowest in PCV13 group, excluding serotype 3). \n7 \n \n \n \n \n  \n   Pivotal Infant  Study \nPost Dose 3 : IgG Concentration and Geometric Mean Ratio \nStatistically Significantly Higher Response when compared to actual PCV13 Response \nComparison of additional 7 serotypes to actual PCV13 IgG GMC, not lowest in PCV20 group \nSerotype \n7 Additional PCV20 \nGMC PCV13 \nGMC GMR \n(95% CI) \n8 1.80 0.02 100.54 (91.58, 110.38) \n10A 1.21 0.01 99.64 (88.87, 111.70) \n11A 1.39 0.02 91.03 (82.79, 100.09) \n12F 0.55 0.01 68.42 (62.47, 74.94) \n15B 4.40 0.03 169.40 (154.01, 186.33) \n22F 3.71 0.01 730.84 (651.36, 820.01) \n33F 1.49 0.02 97.45 (86.96, 109.21) \n0.25 0.5 1 2 4 8 16 32 64 128 256 512 1024 \nGMR \n8 \n      Pivotal Infant  Study \nPost Dose 3: Comparison of PCV20 and PCV13 OPA GMTs \nFunctional Antibody Responses Were Similar Between PCV20 and PCV13 for \nShared Serotypes \nPost Dose 3 \n1 10 100 1000 10000 \n1 3 4 5 6A 6B 7F 9V 14 18C 19A 19F 23F 8 10A 11A 12F 15B 22F 33F OPA GMTs PCV20 PCV13 \nPCV20 (n= 80 –105); PCV13 (n=77 –113). \n9 \n \n \n  \n             Pivotal Infant Study Co-Primary  Objective \nPost Dose 4 : IgG Concentration and Geometric Mean Ratio \nAll 20 Vaccine Serotypes Met Noninferiority \nSerotype \nPCV13 PCV20 \nGMC PCV13 \nGMC GMR Ratio \n(95% CI) \n1 1.47 2.12* 0.69 (0.63, 0.76) \n3 0.56 0.85 0.66 (0.61, 0.73) \n4 3.77 4.84 0.78 (0.70, 0.86) \n5 1.87 2.51 0.74 (0.67, 0.82) \n6A 9.01 11.69 0.77 (0.70, 0.85) \n6B 4.01 5.74 0.70 (0.62, 0.79) \n7F 3.91 5.18 0.76 (0.70, 0.82) \n9V 3.44 4.30 0.80 (0.73, 0.88) \n14 5.68 6.34 0.90 (0.81, 1.00) \n18C 3.46 4.69 0.74 (0.67, 0.82) \n19A 3.53 4.13 0.85 (0.77, 0.94) \n19F 5.01 5.79 0.86 (0.78, 0.96) \n23F 3.95 6.18 0.64 (0.57, 0.72) \n7 Additional \n8 3.97 2.12 1.87 (1.71, 2.06) \n10A 6.22 2.12 2.94 (2.64, 3.26) \n11A 3.53 2.12 1.67 (1.51, 1.84) \n12F 1.85 2.12 0.88 (0.79, 0.97) \n15B 12.59 2.12 5.95 (5.39, 6.55) \n22F 10.60 2.12 5.01 (4.54, 5.52) \n33F 9.31 2.12 4.40 (3.99, 4.85) \n0.25 0.5 1 2 4 8 \nGMR \n* The 7 additional serotypes were compared to serotype 1 in the PCV13 group (lowest IgG GMC after Dose 4, excluding serotype 3). \n10 \n \n  \n     Pivotal Infant Study \nPD3 Compared to PD4: IgG and OPA Response to PCV20 \nBoosting Observed Across All 20 Serotypes Indicating Anamnestic Response/Memory \n11 Post Dose 3 and Post Dose 4 IgG GMCs \nPost Dose 3 and Pose Dose 4 O PA GMTs 0.01 0.1 1 10 100 \n1 3 4 5 6A 6B 7F 9V 14 18C 19A 19F 23F 8 10A 11A 12F 15B 22F 33F IgG GMCs PCV20 PD3 PCV20 PD4 \n1 10 100 1000 10000 100000 \n1 3 4 5 6A 6B 7F 9V 14 18C 19A 19F 23F 8 10A 11A 12F 15B 22F 33F OPA GMTs PCV20 PD3 PCV20 PD4 \nPivotal Infant  Study \nConcomitant Use : Responses to the Vaccines Were Similar When Given \nwith PCV20 or PCV13 in the Infant Immunization Series \nAll Responses Met Noninferiority \nPost Dose 3: Pediarix and Hiberix® \nConcomitant \nVaccine Antigen PCV20 \n(%) PCV13 \n(%) Difference (%) \n(95% CI) \nDiphtheria 93.5 97.8 -4.3 (-7.5, -1.4) \nTetanus 99.7 99.4 0.3 (- 1.0, 1.7) \nPertussis \nPT 94.9 95.0 -0.2 (-3.5, 3.1) \nFHA 95.7 95.0 0.6 (-2.5, 3.9) \nPRN 93.8 95.0 -1.3 (-4.7, 2.2) \nHBsAg 100.0 100.0 0.0 (-3.2, 2.9) \nPoliovirus \nType 1 100.0 100.0 0.0 (- 3.4, 3.2) \nType 2 100.0 99.2 0.8 (- 2.4, 4.6) \nType 3 100.0 100.0 0.0 (- 3.2, 3.1) \nHib 100.0 100.0 0.0 (- 3.0, 3.0) \n-15.0 -5.0 0.0 5.0 15.0 \n% Difference (PCV20 –PCV13)  \n \n \n \n \n \n \n \n \n \n Post Dose 4: MMR ®II and Varivax® \nAntigen \n(Units) PCV20 \nGM PCV13 \nGM GMR \n(95% CI) \n277.74 \n36.96 \n49.63 \n233.05 \n0.25 0.50 1.00 2.00 \nGMR (PCV20:PCV13)   \n \n Measles 215.41 1.29 (1.05, 1.58) (AU/mL) \nMumps 34.19 1.08 (0.85, 1.38) (AU/mL) \nRubella 40.44 1.23 (1.02, 1.48) (IU/mL) \nVaricella 234.78 0.99 (0.84, 1.17) (mIU/mL)  \n         HBsAg = hepatitis B surface antigen; PT = pertussis toxoid, FHA =filamentous hemagglutinin (of Bordetella pertussis ), PRN = pertactin (of Bordetella pertussis ) \n12 \n \n     \n   \n \n \n Pivotal Infant  Study \nSolicited Reactions within 7 Days of Vaccination \nReactions Were Similar in Rate and Severity Across All 4 Doses \nLocal Reactions \n100 \n80 \n60 \n% \n40 \n25.5 24.6 26.4 25.4 27.2 26.6 23.2 23.5 \n16.4 18.8 15.5 17.3 17.1 17.6 14.9 17.3 49.1 45.3 44.1 41.7 38.6 39.0 35.7 35.8 \nDose 1 Dose 2 Dose 3 Dose 4 Dose 1 Dose 2 Dose 3 Dose 4 Dose 1 Dose 2 Dose 3 Dose 4 Redness Swelling Injection Site Pain \nPCV20 PCV13 \nSevere \n20 Moderate \nMild \n0 \nSystemic Reactions \n100 \nFever Decreased Appetite Drowsiness Irritability \n80 70.9 71.7 71.6 68.8 67.2 66.0 64.4 63.0 61.1 61.0 \n60 \n% \n10.3 7.5 17.3 16.3 12.6 13.7 14.5 14.0 24.4 23.9 26.4 23.5 20.6 22.4 24.8 25.2 54.7 55.6 \n44.1 44.1 39.5 39.5 PCV20 PCV13 \n>40.0 °C \nSevere >38.9 –40.0°C \n20 40 \nModerate >38.4 –38.9°C \nMild ≥38.0 –38.4°C \n0 \nDose 1 Dose 2 Dose 3 Dose 4 Dose 1 Dose 2 Dose 3 Dose 4 Dose 1 Dose 2 Dose 3 Dose 4 Dose 1 Dose 2 Dose 3 Dose 4 \nPCV20: Dose 1=993, Dose 2=940, Dose 3=914, Dose 4=826. PCV13: Dose 1=974, Dose 2=924, Dose 3=901, Dose 4 =814. \n13 \n  \n      \n \n \n \n  \n     \n \n  \n      \n \n \n \n  \n    1523 mos\nN†=2092 4 yrs\nN†=2165 9 yrs\nN†=2011017 yrs\nN†=216\nSex n‡(%) n‡(%) n‡(%) n‡(%)\nMale 117 (56.0) 106 (49.1) 108 (53.7) 115 (56.1)\nRace\nWhite 168 (80.4) 173 (80.1) 174 (86.6) 178 (86.8)\nBlack or African\nAmerican26 (12.4) 26 (12.0) 22 (10.9) 17 (8.3)\nAsian 3 (1.4) 0 0 0\nAmerican Indian or Alaska Native0 1 (0.5) 0 0\nNative Hawaiian or \nother Pacific Islander0 0 0 1 (0.5)\nMultiracial 10 (4.8) 13 (6.0) 5 (2.5) 9 (4.4)\nEthnicity\nHispanic/Latino 35 (16.7) 45 (20.8) 31 (15.4) 43 (21.0)\nNon Hispanic/Latino 172 (82.3) 171 (79.2) 168 (83.6) 161 (78.5)– – – –\n-Demographic Characteristics – \nSafety Population \n15–23 mos 2 –4 yrs 5 –9 yrs 10–17 yrs \nN†=209 N†=216 N†=201 N†=216 \nSex n‡ (%) n‡ (%) n‡ (%) n‡ (%)\nMale 117 (56.0) 106 (49.1) 108 (53.7) 115 (56.1) \nRace \nWhite 168 (80.4) 173 (80.1) 174 (86.6) 178 (86.8) \nBlack or African \nAmerican 26 (12.4) 26 (12.0) 22 (10.9) 17 (8.3) \nAsian 3 (1.4) 0 0 0 \nAmerican Indian or Alaska Native 0 1 (0.5) 0 0 \nNative Hawaiian or \nother Pacific Islander 0 0 0 1 (0.5) \nMultiracial 10 (4.8) 13 (6.0) 5 (2.5) 9 (4.4) \nEthnicity \nHispanic/Latino 35 (16.7) 45 (20.8) 31 (15.4) 43 (21.0) \nNon-Hispanic/Latino 172 (82.3) 171 (79.2) 168 (83.6) 161 (78.5)       \n    \n       Phase 3 Study \nAge Prior \nGroup Vaccination Status Day 1 1 month 6 months \nPCV20 Group  \n         Pediatric Single Dose Study Design and Demographics Single Dose Study \nPCV20\n ≥3 doses of PCV13 \n15–23 \nmonths* \n2–4 \nyears* \n5–9 \nyears \n10–17 \nyears \nBlood draws PCV20\n ≥3 doses of PCV13 \nPCV20\n Not required \nPCV20\n Not required \nSafety follow -up call \n*Participants <5 years of age had confirmed receipt of >3 prior doses of PCV13. \n† N=number of participants in the specified age cohort. This value is the denominator for the percentage calculations. ‡ n=nu mber of participants with the specified characteristic. \n14 \n \n \n \n IgG GMC in Children Previously Vaccinated with PCV13 \nOne Dose of PCV20 Elicited Responses to All Vaccine Serotypes Single Dose Study \n15 15 to <24 Months \n2 to <5 Years 0.01 0.1 1 10 100 \n1 3 4 5 6A 6B 7F 9V 14 18C 19A 19F 23F 8 10A 11A 12F 15B 22F 33F IgG GMCs \nBefore PCV20 1 Month After PCV20 \n0.01 0.1 1 10 100 \n1 3 4 5 6A 6B 7F 9V 14 18C 19A 19F 23F 8 10A 11A 12F 15B 22F 33F IgG GMCs \nBefore PCV20 1 Month After PCV20 \nOverall  Safety \nOverall Summary of Adverse Events in the US \nPCV20 had no Related Serious Adverse Events or Deaths \nAge < 15 months \n16 *SAEs reported  are  in all  sites,  not  just  US (including  Puerto  Rico). \nB7471003, B7471011,  and  B7471013 (all  sites) : (PCV20 N=2232;  PCV13 N=1717)   \n   \n 15 m -<18 yr \nPCV20 \n(N=1567) PCV13 \n(N=1376) PCV20 \n(N=831) \nAEs 43.8% 46.3% 10.7% \n Immediate AEs 0.1–0.2% /dose 0.1% /dose 0% \n Related AE 1.1% 1.1% 0.1% \n Severe AEs 1.4% 1.1% 0.2% \nSerious AEs* 4.5%* 3.7%* 0.6% \n Related SAEs 0 0 0 \nDeaths 0 0 0 \n \n       \n   \n          \n  \n       \n    Summary of PCV20 Pediatric \nPCV20 is well tolerated with a safety profile similar to PCV13 \nThe totality of data shows PCV20 elicits immune responses to all 20 vaccine serotypes \nA single dose of PCV20 elicited a robust immune response to all 20 serotypes and was well tolerated in \nchildren 15 months to < 18 years of age, including those with prior PCV13  \nPCV20 is compatible with routine pediatric vaccines \nPCV20 is currently under review by the FDA for use in pediatric population 6 weeks to <18 years of age \nwith a target action date in April 2023 \nPCV20 has the potential to address a substantial burden of pneumococcal disease in children \n17 \nQuestions? \n18", "summary": "20-valent Pneumococcal  Conjugate Vaccine  (PCV20) Phase 3  in Pediatrics  Wendy Watson, MD  Global Clinical Program Lead  ACIP February 22, 2023  1  PCV20 is Built on the Established Platforms of PCV7 and PCV13  • PCV20 builds on the 20 -year legacy of PCVs and contains PCV13 components + conjugates for 7 additional PCV20  Composition serotypes to broaden disease coverage for pneumococcal disease in children  • The 7 additional conjugates were modelled on the PCV13 Pfizer platform  •…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/Pneumococcal-04-Watson-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 18}
{"title": "Pneumococcal 05 Kobayashi 508", "content": "Nationa  l Center  for  Immunizatio  n &  Respirator  y Diseases \n     \n        \n   \n   \n    \n  Evidence to Recommendations Framework (Preliminary): \nUse of 20-valent Pneumococcal Conjugate Vaccine in U.S. Children \nMiwako Kobayashi, MD, MPH \nPneumococcal Vaccines Work Group \nAdvisory Committee on Immunization Practices \nFebruary 22, 2023 \n    \n        \n        \n      \n       \n           \n           \n   \n         \n      \n     \n          \n          Evidence to Recommendations (EtR) framework \nEtR Domain Question \nPublic Health Problem • Is the problem of public health importance? \nBenefits and Harms • How substantial are the desirable anticipated effects? \n• How substantial are the undesirable anticipated effects? \n• Do the desirable effects outweigh the undesirable effects? \n• What is the overall certainty of this evidence for the critical outcomes? \nValues • Does the target population feel the desirable effects are large relative \nto the undesirable effects? \n• Is there important variability in how patients value the outcomes? \nAcceptability • Is the intervention acceptable to key stakeholders? \nFeasibility • Is the intervention feasible to implement? \nResource Use • Is the intervention a reasonable and efficient allocation of resources? \nEquity • What would be the impact of the intervention on health equity?2 \n    \n        \n        \n      \n       \n           \n           \n   \n         \n      \n     \n          \n          Values •Does the target population feel the desirable effects are large relative\nto the undesirable effects?\n•Is there important variability in how patients value the outcomes?\nAcceptability •Is the intervention acceptable to key stakeholders?\nFeasibility •Is the intervention feasible to implement?\nResource Use •Is the intervention a reasonable and efficient allocation of resources?Evidence to Recommendations (EtR) framework \nEtR Domain Question \nPublic Health Problem • Is the problem of public health importance? \nBenefits and Harms • How substantial are the desirable anticipated effects? \n• How substantial are the undesirable anticipated effects? \n• Do the desirable effects outweigh the undesirable effects? \n• What is the overall certainty of this evidence for the critical outcomes? \nEquity • What would be the impact of the intervention on health equity?3 \n         \n  \n      \n    \n \n       All children under age 2 years have the same \npneumococcal vaccine recommendations \n• 3 primary series and a booster=“3+1” schedule \nPCV PCV PCV PCV 2months 4months 12–15 months 6months \nPrimary Series Booster \nEither PCV13 or PCV15 can be used for U.S. children. \n4 \n        \n  \n      \n    \n \n                  \n    \n     \n      Primary Series Booster\nCurrently, either PCV13 or PCV15 can be used for U.S. children.All children under age 2 years have the same \npneumococcal vaccine recommendations \n• 3 primary series and a booster=“3+1” schedule \nPCV PCV PCV PCV 2months 4months 12–15 months 6months \nShould PCV20 be recommended as an option for \npneumococcal conjugate vaccination according to currently recommended dosing and schedules, for U.S. children aged <2 years? \n5 \n        \n     \n \n \n \n   \n  \n  \n   \n \n   \n Children age ≥2 years with certain underlying conditions \nrecommended to receive PPSV23 in addition \nPPSV23 Recommended \nPCV doses Recommended \nPCV doses Healthy \nchildren \nMC, CSF leak, \ncochlear \nimplant \n≥8 weeks \nRecommended \nPCV doses PPSV23 PPSV23 Immuno-\nompromised \n≥8 weeks ≥5 years \nMC aged 6–18 \nyears PPSV23 \n                 \n         \n           \n  C\nc\nC\nNote: Excludes catch-up vaccination schedules. \nCMC=chronic medical conditions, including chronic heart disease, chronic lung disease, diabetes mellitus \nCSF=cerebrospinal fluid \nUse of 15-Valent Pneumococcal Conjugate Vaccine Among U.S. Children: Updated Recommendations of the Advisory Committee on Immunization \nPractices — United States, 2022 | MMWR (cdc.gov) 6 \n      \n       \n       \n       \n \nShould PCV20 without PPSV23 be recommended \nas an option for pneumococcal vaccination for U.S. children aged 2–18 years with underlying \nmedical conditions that increase the risk of pneumococcal disease? \n7 \n           \n  \n           \n  \n    \n     \n         \n      \n  \n         PICO \nQuestion Should PCV20 be recommended as an option for pneumococcal vaccination \nfor U.S. children? \nPopulation U.S. children aged 2–18 years with All U.S. children aged <2 years underlying medical conditions \nIntervention PCV20 according to currently \nrecommended dosing and PCV20 (without PPSV23) schedules \nComparison PCV13 or PCV15 according to currently recommended dosing and schedules \nOutcomes VT-IPD, VT- pneumonia, VT- AOM, VT- pneumococcal deaths, serious adverse events following vaccination \n8 VT: vaccine-type, IPD: invasive pneumococcal disease, AOM: acute otitis media \nEtR Dom  ain: P  ublic Healt  h Problem \n     \n \n          \n    \n          \n          \n           \n     \n          \n    \n    \n     \n     Summary of pneumococcal disease epidemiology \nin children \n• Use of PCVs (PCV7, PCV13) significantly decreased the incidence of \npneumococcal disease in U.S. children. \n• Outpatient ARIs caused by pneumococcus, such as AOM, sinusitis, and pneumonia, are common causes of outpatient visits and antibiotic prescribing. \n• Risk of disease remains high in children with underlying conditions that increase the risk of pneumococcal disease. \n• In 2018–2019, the proportion of IPD caused by vaccine serotypes was: \n• PCV20, non-PCV13: ~30% of IPD \n• PCV15, non-PCV13: ~15% of IPD \nGierke. February 2023 ACIP meeting presentation \nKing. February 2023 ACIP meeting presentation 10 \n  \n         \n Public Health Problem \nIs pneumococcal disease of public health importance in U.S. \nchildren? \n□\n□□□□□ N o \n Probably  no \n Probably  yes \n Yes  Varies  Don’t  know \n11 \n  \n         \n \n     \n        \n    \n      \n         \n  Public Health Problem \nIs pneumococcal disease of public health importance in U.S. \nchildren? \n□ \n□ □ □ □ □ N o \nProbably  no \nProbably  yes \nYes Varies Don’t  know • Variability in Work Group members’ \ninterpretations for children aged <2 years due to significant reductions in pneumococcal disease. \n• Most agreed that pneumococcal disease continues to be of public health importance due to the remaining disease burden. \n12 \nEtR Dom  ain: Benefits   and Harms \n \n  \n  \n  \n     \n     \n    \n   \n  \n       \n Outcomes (Benefits) \nOutcome Importance Description \nVT- IPD Critical Studies assessing PCV20 against these \nVT- non-bacteremic \npneumococcal pneumonia clinical outcomes are currently not Critical \navailable \nVT- acute otitis media  PCV20 immunogenicity studies for Critical GRADE \nVT- pneumococcal deaths Critical  PCV13/PPSV23 clinical outcome studies for background \nAOM=acute otitis media, IPD=invasive pneumococcal disease, VT=vaccine-type 14 \n \n \n       Outcomes (Harms) \nOutcome Importance Description \nSerious adverse events Critical Safety data for PCV20 are available \n15 \nBackground \n     \n  \n   \n \n \n \n            \n             \n            PCV13 effectiveness (3+1) in children, VT-IPD \nStudy Population Dosin  g schedule  \n(Ye  ar o  f \nintroduction) Me thod Outcome Vaccine (95% CI) \nEffectiveness \nSavulescu, \n2022 Children 2m – 59m; Spidnet \n(12 European 2+1 or 3+1 \n(variable) Indirect cohort 3 + 1 doses, ≥12 months 89.7% (adjusted*) (82, 94) \nsites, 2012 -\n2018 \nV an \nde  r \nLinden,  \n2016* Childre  n <2  \nyears;  German  y \n(GNRCS) 3+1  (Decembe  r \n2009) Indirec  t \ncohort PCV13-type;  post-booster 91% (61,  99) \nWeinberger,  \n2016 Childre  n 2.5  – \n56m;  German  y \n(ESPED) 3+1  (Decembe  r \n2009) Indirec  t \ncohort PCV13-type  +6C;  ≥2  dose  before  12  \nmonths  or one  dose  on/afte  r 12  \nmonths 85%  (adjusted) (64,  94) \nDominguez,  \n2017 Childre  n 7m  -\n59m;  Sp  ain \n(Catalonia) 3+1  (public,  Ju ly \n2016) Matche  d \ncase-\ncontrol PCV13-type;  7-59m;  ≥2  doses  before  \n12 months  o r one  dose  afte  r 12  \nmonths 78.9% (52.8,  90.5) \nMoore  , \n2016 Childre  n 2-\n59m;  US 3+1  (2010) Matche  d \ncase-\ncontrol PCV13-type;  ≥1  dose 86.0%  \n(unadjusted) (75.5,  92.3) \n* Adjusted by site, age, year of notification and at least one underlying disease \nPost-licensure vaccine effectiveness studies have shown that PCV13 is highly effective against \nVT-IPD 17 \n   \n  \n   \n \n     \n      \n         \n       \n PCV13 effectiveness, VT-pneumococcal pneumonia \nStudy Population Dosing schedule \n(Year of introduction) Method Outcome VE (95% CI) \nZhang, 2021 Children  born  \nD\necember  2016  \n– Novembe  r \n2018,  China 3+1  (2017) Indirect  cohort; \nVT-CAP  defined  as  hospita  l \ndischarge  diagnosis code  of  \npneumonia  +  deep  uppe  r \nrespiratory  aspirate  with  \nPCV13  serotypes.  VT-CAP;  ≥3  \ndoses 62.1  % \n(adjusted) (26.3  , 80.5) \nLew\nnard, \n2021* Children 4 to 59 \nmonths, Israel 2+1 (2010) Nested  c ase-control  ; \nUsed: • PCV-conferred  protection  \nagainst VT  pneumococca  l \ncarriage \n• Protection  agains  t \nprogression  fr  om carriage  t o \npneumonia CAP attributed  \nt o PCV13  , 12-\n59  months;  2+1  \ndoses 77\n.0 % \n(adjusted) (-16.0, 100.0) \nCAP=community acquired pneumonia \n*funded by Pfizer Limited data on PCV13 effectiveness against VT-pneumococcal \npneumonia in children. PCV13 likely protective. 18 \n  \n  \n   \n \n    \n          \n     \n          \n        \n          \n    PCV13 effectiveness, VT-AOM \nStudy Population Dosing schedule \n(Year of introduction) Method Outcome VE (95% CI) \nPichichero, \n2018* Children  ≤ 36  \nmonth  s, United  \nStates 3+1  (2010) Prospective  \nlongitudina  l \ncohor  t (PCV1  3 v  \nPCV  7 period) PCV13-non-PCV7 serotype  s; \nPCV1  3 full  primar  y serie  s \n(regardle  ss of  booste  r statu  s) \nvs. PCV7  f or middle-ear  flui  d \nsamples  a t onse  t of  AOM \nSerotype  3; PCV13  ful l \nprimary  serie  s (regardle  ss of  \nbooste  r status)  vs. PCV  7 f  or \nmiddle-ear  fluid  samples  a t \nonse  t of  AOM 86  % \n(adjusted) \n5 % \n(adjusted) (61 , 94) \n(–181  , 68) \nOc\nhoa-\nGondar, 2015 ≤14 years; Spain \n(Catalonia region) 3+1 (2016, publicly available) Indirect cohort PCV13-type; ≥1 dose 62% (unadjusted) (-141, 95) \nDagan, 2021* Children 5 to 35 months, Israel 2+1 (2010) Nested case-control PCV13-type; ≥2 doses vs. 0 doses 77.4% (adjusted) (35.3, 92.1) \nSerotype 3; ≥2 doses vs. 0 doses 89.0% (adjusted) (23.9, 98.4) \nLimited data on PCV13 effectiveness against VT-pneumococcal AOM in \nchildren. PCV13 likely protective. *funded by Pfizer 19 \n     \n          \n     PPSV23 effectiveness, VT-IPD (Pre-PCV U.S. data) \nPre-PCV era data showed that PPSV23 is protective against VT-IPD among \nchildren with underlying medical conditions. \n    Fiore et al. EID 1999 20 \n    \n            \n       \n \n     \n     \n    \n      PPSV23 effectiveness, non-invasive pneumococcal \ndisease \n• No study on PPSV23 VE against AOM identified in a recent systematic review1 \n• Two randomized-controlled trials (RCTs)2,3 evaluated PCV7-PPSV23 in series \nagainst AOM \n• No efficacy in the PCV7-PPSV23 groups \n1. Marra et al. Value Health 2022 \n2. Veenhoven et al. Lancet 2003 \n3. Van Kempen et al. Int J Pediatr Otorhinolaryngol 2006 21 \nGRADE:  PCV2  0 us  e  in children \n     \n       Evidence retrieval: PCV20 use in children \nClinicaltrials.gov \nN=12 \n4 studie  s include  d fo  r GRADE \nPhase  I I tria  l (published),  N=1 \nPhase  II I trial  s (unpublished),  N=3 Pubmed \nN=62 \nPCV20  routi  ne use \n(N=3) \nImmunogenicity  (N=2) \nSafety  (N=3) PCV20   use i  n childre  n \nwit  h underlyi  ng \nconditions \n(N=1) \nImmunogenicity  (N=1) \nSafety  (N=1) Unpublishe  d data  from  \npharmaceutica  l \ncompany \nN=3 \n23 Search terms used are provided in supplementary slides \n   \n    \n         \n       \n    \n  \n           \n  \n   \n           \n   \n         \n       \n     \n              \n    \n    Summary of evidence: \nBenefits, children <2 years \n• Informed by 2 randomized controlled trials (Phase II and III)1,2 \n• Healthy children randomized to either PCV13 or PCV20 \n• PCVs given using 3+1 schedule \n• Summary of findings \n•PCV20 had numerically lower immune responses* vs. PCV13 for most of the \n13 shared serotypes \n•Post dose 3 : \n•PCV20 did not meet noninferiority criteria vs. PCV13 for some serotypes \n•Post dose 4 : \n•PCV20 noninferior to PCV13 for all 13 shared serotypes \n•PCV20 noninferior to PCV13** for all 7 additional serotypes \n*measured as IgG GMCs and GMRs \n**Compared with the serotype with lowest immune response among PCV13 serotypes except for serotype 3 \n1. Senders et al. PIDJ 2021 \n2. Pfizer unpublished data from B7471011 24 \n   \n    \n             \n \n      \n     \n    \n   \n          Summary of evidence: \nHarms, children <2 years \n• Serious adverse events (SAEs) across 3 studies (dose 1 through 6 months after \ndose 4): \n• PCV20: 4.5% (n=1,567) vs PCV13: 3.7% (n=1,376) \n• None were considered to be vaccine-related \n1. Senders et al. PIDJ 2021 \n2. Pfizer B7471011, unpublished data \n3. Pfizer B7471013, unpublished data, limited to US and Puerto Rico sites 25 \n          \n          \n   \n  \n   \n \n \n  \n         Should PCV20 be recommended as an option for pneumococcal conjugate \nvaccination according to currently recommended dosing and schedules, for U.S. children aged <2 years? \nType Outcome Importance Included in \nevidence profile Certainty for \nhealthy individuals \nVT- IPD Critical Yes Moderate \nBenefits VT-pneumonia Critical Yes Moderate \nVT- AOM Critical Yes Moderate \nVT- pneumococcal \ndeaths Critical Yes Moderate \nHarms SAEs following \nvaccination Critical Yes Moderate \nAOM=acute otitis media, IPD=invasive pneumococcal disease, SAE=serious adverse events, VT=vaccine-type 26 \n  \n     \n       \n    \n   \n \n    \n   \n     \n   Benefits and Harms \nHow substantial are the desirable anticipated effects? \n Routine PCV20 use for children aged <2 years \n□ Minimal \n Small \n Moderate  Large  Varies  Don’t  know □□□□□• PCV20 provides the broadest \nserotype coverage among available PCVs. \n• Unknown how substantial the protection conferred from PCV20 will be based on available data. \n27 \n  \n     \n        Benefits and Harms \nHow substantial are the undesirable anticipated effects? \n Routine PCV20 use for children aged <2 years \n□ Minimal \nSmall \nModerate Large Varies Don’t  know □ □ □ □ □ \n28 \n  \n       \n       \n  \n  \n   Benefits and Harms \nDo the desirable effects outweigh the undesirable effects? \n Routine PCV20 use for children aged <2 years \n□ Favor  s intervention* \n Favor  s current  recommendation\n Favor  s both \n Favor  s neither \n Varies \n Don’t  know □  \n□□□□\n*Intervention: PCV20 use \nComparison: PCV13 or PCV15 use 29 \n  \n       \n       \n  \n           \n \n    \n         \n         \n      Benefits and Harms \nDo the desirable effects outweigh the undesirable effects? \n• Routine PCV20 use for children aged <2 years \nFavors Intervention (PCV20): \n• PCV20 is expected to prevent more disease compared with current PCVs (PCV13, PCV15) \nFavors Both (PCV20 or PCV13/PCV15): • Clinical implications of the lower immunogenicity PCV20 compared with PCV13 \nunknown \n• Clinical implications of improved immunogenicity of PCV15 against serotype 3* \nunknown \n*Banniettis. February 24, 2022 ACIP meeting presentation 30 \n   \n       \n        \n        \n            \n        \n  \n           \n   \n        \n    Summary of evidence: \nBenefits, children 2–18 years with underlying conditions \n• No studies conducted among children with underlying medical conditions \n• Informed by 1 non-randomized trial (Phase III), no comparator \n• Healthy children aged 15 months to 17 years received a dose of PCV20 \n• Children aged <5 years received ≥3 doses of PCV13 \n• Summary of findings \n•PCV20 was immunogenic* for all 20 vaccine serotypes 1 month after \nvaccination vs. pre-vaccination. \n*Measured as IgG GMCs and GMFR and OPA GMFRs \nPfizer unpublished data from B7471014 31 \n   \n      \n    \n   \n     \n    Summary of evidence: \nHarms, children 2–18 years with underlying conditions \n• Serious adverse events (SAEs) : \n• PCV20: 0.6% (n=831) \n• None were considered to be vaccine-related \nPfizer unpublished data from B7471014 32 \n           \n            \n     \n      \n  \n \n \n \n  \n   \n         Should PCV20 without PPSV23 be recommended as an option for pneumococcal \nvaccination for U.S. children aged 2–18 years with underlying medical conditions that increase the risk of pneumococcal disease? \nType Outcome Importance Included in evidence \nprofile Certainty for children \nwith underlying \nconditions \nVT-IPD Critical Yes Very Low \nBenefits VT-pneumonia Critical Yes Very Low \nVT-AOM Critical Yes Very Low \nVT-pneumococcal \ndeaths Critical Yes Very Low \nHarms SAEs following \nvaccination Critical Yes Very Low \nAOM=acute otitis media, IPD=invasive pneumococcal disease, SAE=serious adverse events, VT=vaccine-type 33 \n  \n     \n           \n    \n   \n \n    \n    \n      \n     Benefits and Harms \nHow substantial are the desirable anticipated effects? \n PCV20 use for children aged 2–18 years with underlying medical conditions \n□ Minimal \n Small \n Moderate  Large  Varies  Don’t  know □□□□□• PCV20 provides the broadest \nserotype coverage among available PCVs. \n• Unknown how substantial the protection conferred from PCV20 will be based on available data. \n• No data from this population. \n34 \n  \n     \n            Benefits and Harms \nHow substantial are the undesirable anticipated effects? \n PCV20 use for children aged 2–18 years with underlying medical conditions \n□ Minimal \n Small \n Moderate  Large  Varies  Don’t  know □□□□□\n35 \n  \n       \n           \n  \n  \n   \n      Benefits and Harms \nDo the desirable effects outweigh the undesirable effects? \n PCV20 use for children aged 2–18 years with underlying medical conditions \n□ \n□ \n□ □ □ □ Favor  s intervention* \nFavor  s current  recommendation \nFavor  s both \nFavor  s neither \nVaries Don’t  know *Intervention: PCV20 use \nComparison: PPSV23 use after currently \nrecommended PCV (PCV13 or PCV15) doses \n36 \n  \n       \n          \n  \n         \n     \n        \n       \n          \n       Benefits and Harms \nDo the desirable effects outweigh the undesirable effects? \n PCV20 use for children aged 2–18 years with underlying medical conditions \nFavors Intervention (PCV20): \n• PCV20 is expected to prevent more disease compared with current recommendations (PPSV23 after recommended PCV13/15 doses) \nFavors Both (PCV20 or PPSV23 after recommended PCV13/PCV15 doses): • No data on PCV20 use in this population \n• Clinical implications of improved immunogenicity of PCV15 against serotype 3* \nunknown \n*Banniettis. February 24, 2022 ACIP meeting presentation 37 \nEtR Dom  ain: Equity \n       \n        \n      \n      \n   \n \n \n  \n     \n    Compared with coverage among children with private \ninsurance only , children who were uninsured, and those \ninsured by Medicaid and other insurance was lower \n≥3 PCV doses (%) ≥4 PCV doses (%) \nPrivate insurance only (Ref) \n(N=16,629) 96.2 90.0 \nAny Medicaid (N=10,200) 91.3* 78.8* \nOther insurance (N=2,168) 91.1* 80.6* \nUninsured (N=608) 83.9* 62.3* \nPCV=pneumococcal conjugate vaccine \n*statistically significant difference compared with Ref. \nHill et al. MMWR 2023 39 \n     \n      \n          \n        \n        \n          \n \n  \n           \n       \n       \n      \n      \n    Nationally representative PPSV23 vaccine coverage \ndata among children with indications are limited \n• Vaccine coverage among children with sickle cell anemia, Michigan Medicaid program1 \n• 4PCV + 1 PPSV23 at age 5 years: 64% \n• 4PCV + 2 PPSV23 at age 10 years: 53% \n• Self-administered survey of parents/guardians of children aged <18 years with \nnephrotic syndrome2 \n• PPSV23 receipt: 43% \n• Data from single-center quality improvement studies among children seen in specialty \ncare clinics reported 20–30% PPSV23 coverage at baseline3,4 \n1. Reeves et al. Pediatric Blood & Cancer, 2018 \n2. Tran et al. Frontiers in Pediatrics, 2021 \n3. Mirza et al. The Ochsner Journal, 2022 40 4. Harris et al. Pediatrics, 2022 \n  \n  \n  \n  \n  \n \n     \n \n41IPD incidence \nrate difference \nin children aged ≤17 years by census tract poverty, \nABCs 2010–2019 \nCDC ABCs, unpublished data All Serotypes PCV13 Serotypes PCV15/non-PCV13 \nPCV20/non-PCV13 PCV20/non-PCV15 Nonvaccine Serotypes \n  \n  \n  \n  \n  \n \n     \n          \n        \n      \n42IPD incidence \nrate difference \nin children aged ≤17 \nNonvaccine Serotypes \nyears by census tract poverty, \nABCs 2010–2019 \nCDC ABCs, unpublished data PCV15/non-PCV13 \nPCV20/non-PCV13 PCV20/non-PCV15 For all serotypes and PCV13 serotypes, IPD incidence rate \ndifference between the highest and lowest census tract poverty categories decreased after PCV13 introduction. All Serotypes PCV13 Serotypes \n  \n  \n  \n  \n  \n \n     \n         \n   \n43IPD incidence \nrate difference \nin children aged ≤17 years by census tract poverty, \nABCs 2010–2019 \nCDC ABCs, unpublished data All Serotypes PCV13 Serotypes PCV15/non-PCV13 \nPCV20/non-PCV13 PCV20/non-PCV15 Nonvaccine Serotypes Essentially no IPD incidence rate difference for the \nPCV15, non-PCV13 serotypes. \n  \n  \n  \n  \n  \n \n     \n         \n   \n       \n44All Serotypes PCV13 Serotypes PCV15/non-PCV13 \nIPD incidence \nrate difference \nin children aged ≤17 years by census tract poverty, \nABCs 2010–2019 \nCDC ABCs, unpublished data PCV20/non-PCV13 PCV20/non-PCV15 Nonvaccine Serotypes • IPD incidence rate difference for the additional serotypes \ncontained in PCV20 remain \n• Slightly larger incidence rate difference for non-vaccine serotypes \n          \n   Equity \nWhat would be the impact of recommending PCV20 for U.S. \nchildren on health equity? \n□ Reduced \n Probably  reduced \n Probably  n o impact \n Probably  increased \n Increased \n Varie  s \n Don’t  kno  w □\n□\n□\n□\n□\n□\n45 \n          \n      \n \n           \n         \n  \n         \n \n          \n  Equity \nWhat would be the impact of recommending PCV20 for U.S. \nchildren aged <2 years on health equity? \nProbably reduced: \n• New interventions are likely to be accessible to wealthy communities, first \nVFC program mitigates inequities in access to recommended vaccines \nProbably no impact: • Remaining disparities in vaccine-type disease seem to be minimal \nProbably increased: • Post-PCV13 data showed that PCV13 reduced disparities in vaccine-type disease \nVFC=Vaccines for Children \n          \n        \n  \n  \n           \n  \n \n         \n   Equity \nWhat would be the impact of recommending PCV20 for U.S. \nchildren aged 2–18 years with underlying medical conditions \non health equity? \nProbably no impact: \n• Risk-based recommendation is less likely to be equitable compared with routine \nvaccine recommendations. \nProbably increased: \n• PCV20 use could simplify the pneumococcal vaccine recommendations and \nimprove vaccine coverage. \n        \n       \n  \n  \n  \n \n    \n      \n      \n   Summary of Work Group Interpretation of the EtR Domains (Preliminary) \nEtR Domains PCV20, <2 years (routine) PCV20, 2–18 years old \nPublic Health Problem Yes \nBenefits and Harms \na. Benefits Moderate \nb. Harms Minimal \nc. Benefit>Harm? Favors intervention/Favors both (split) \nd. Overall certainty: \neffectiveness 2 (moderate) 4 (very low) \ne. Overall certainty: safety 2 (moderate) 4 (very low) \nEquity Probably increased (different opinions) \n48 \n      \n          \n          \n          \n   Acknowledgements \n• ACIP and the Pneumococcal Vaccines Work Group \n• CDC contributors and consultants: Ryan Gierke, Jennifer Farrar, Kristin Andrejko, \nLindsay Zielinski, Emma Accorsi, Adam Cohen, Alison Albert, Noele Nelson, Pedro Moro, Elizabeth Velazquez, Marc Fischer, Katie Hamilton, Noelle Sobotka, Rebecca Morgan, Doug Campos-Outcalt \n49 \nSupplementar  y Slides\nGRADE  Summary  of Evidence  \nSearch strategy: PCV20 use in children \nNo. \nDatabase Strategy identified \nClinicaltrials.gov Inclusion: Relevant Phase 2, or 3 randomized controlled trials of PCV20 \n• Involved human subjects \n• Reported primary data \n• Included infants and children (age ≤18 years) \n• Included data relevant to the efficacy or effectiveness or immunogenicity and safety \noutcomes being measured \n• Included data for the dosage and timing being recommended: \no 3+1 series for infants starting the vaccine series as currently recommended \no Catch-up vaccine schedule for older infants and children who did not start the 3+1 series \nin time \no Use of PCV20 to complete the PCV13 series \no Use of PCV20 in series with PPSV23 in older children with underlying conditions in series \nwith PPSV23 Included  in  \nGRADE \n12 3* \nPubmed \nMedline “PCV20” or “20-valent pneumococcal conjugate vaccine” Included studies using the criteria listed above 62 1 \nAdditional resources Unpublished and other relevant data by consulting with the vaccine manufacturer \n2 3*      \n \n          \n  \n  \n                  \n  \n        \n          \n               \n \n       \n               \n \n      \n      \n           \n             \n \n \n \n \n \n \n \n \n*Same trials. Unpublished data from these trials were obtained from pharmaceutical companies. 51 \n         \n       \n    \n  \n      \n     \n  \n    \n   \n  \n      \n   \n   \n  \n  \n    \n   \n       \n   \n   \n \n \n \n \n  \n  \n  \n  Included Studies: Routine PCV20 Use in Children Aged <2 years \nAuthor, year Study \ndesign Intervention Country Age Total population N Intervention N comparison Outcomes Funding source \nPhase II RCT 42–98 \nSenders, 2021 in healthy full-term \ninfants PCV20 @ 2, 4, 6, \nand 12 months of age US days of age at \nconsent 460 232 228 Immuno-\ngenicity and safety Pfizer \nB7471011 Phase III RCT \nin healthy full-term \ninfants PCV20 @ 2, 4, 6, \nand 12 – 15 months of age US, Puerto Rico 42–98 \ndays of age at \nconsent 1998 1001 997 Immuno-\ngenicity and safety Pfizer \nUS, Puerto 42–98 \nB7471013 Phase III RCT in healthy infants PCV20 @ 2, 4, 6, and 12 – 15 months of age Rico, \nCanada, \nChile, Argentin a, EU days of age at \nconsent 1511 1000 551 Safety Pfizer \n52 \nRCT=Randomized Controlled Trial \nCertainty assessment № of patients Results \nCertainty Importance № of \nstudies Study \ndesign Risk of \nbias Inconsistency Indirectness Imprecision Other \nconsiderations Intervention comparison Relative \n(95% CI) Absolute \n(95% CI)    \n      \n  \n \n        \n   \n      \n  \n    \n   \n    \n    \n     \n   \n   \n     \n  -Vaccine effectiveness \n21 2 RCT Not \nserious Not serious Seriousa Not serious Not serious 921-1022 910-989 • PCV20 had numerically lower \nimmune responses compared with PCV13 for most of the \n13 shared serotypes. \n• PCV20 did not meet \nnoninferiority criteria for some serotypes after dose 3. \n• PCV20 noninferior to PCV13 for all 13 shared serotypes after dose 4. \n• PCV20 noninferior to PCV13\nb \nfor all 7 additional serotypes after dose 4. Moderate Critical GRADE Summary of Findings: Routine PCV20 use in Children Aged <2 Years            \n               \n             \n                                           \n  \n                    a. These are all immunogenicity studies and there are no correlates of protection for most outcomes. \nb. Compared with serotype with lowest immune response among PCV13 serotypes except for serotype 3 \nReferences \n1. Senders S, Klein NP, Lamberth E, Thompson A, Drozd J, Trammel J, Peng Y, Giardina PC, Jansen KU, Gruber WC, Scott DA, Watson W. Safety and Immunogenicity of a 20-valent Pneumococcal Conjugate Vaccine in Healthy Infants in the United States. Pediatr Infect Dis J. 2021 Oct \n1;40(10):944-951. doi: 10.1097/INF.0000000000003277. 53 2.B7471011. A Phase 3, Randomized, double-blind trial to evaluate the safety and immunogenicity of a 20-valent pneumococcal conjugate vaccine in healthy infants \nCertainty assessment № of patients Results \nCertainty Importance № of \nstudies Study \ndesign Risk of \nbias Inconsistency Indirectness Imprecision Other \nconsiderations Intervention Comparison Relative \n(95% CI) Absolute \n(95% CI) \nSerious Adverse Events (SAEs) following vaccination    \n      \n  \n     \n        \n   -21 3 RCT Not Not serious Not serious Seriousa Not serious 4.5% 3.7% No vaccine-related \nserious (n=1567) (n=1376) serious adverse events Moderate Critical \nreported GRADE Summary of Findings: Routine PCV20 use in Children Aged <2 Years            \n   \n   \n                             \n               \n                     \n                            a. No v\naccine-related serious adverse events reported \nReferences \n1.Senders S, Klein NP, Lamberth E, Thompson A, Drozd J, Trammel J, Peng Y, Giardina PC, Jansen KU, Gruber WC, Scott DA, Watson W. Safety and Immunogenicity of a 20-valent Pneumococcal Conjugate Vaccine in Healthy Infants in the United States. Pediatr Infect Dis J. 2021 Oct 1;40(10):944-951. doi: 10.1097/INF.0000000000003277. 2.B7471011. A Phase 3, Randomized, double-blind trial to evaluate the safety and immunogenicity of a 20-valent pneumococcal conjugate vaccine in healthy infants 3.B7471013. A Phase 3, Randomized, double-blind trial to evaluate the safety of a 20-valent pneumococcal conjugate vaccine in healthy infants. Data limited to U.S. and Puerto Rico sites. \n54 \nIncluded Study: PCV20 Use in Children Aged 2–18 Years with Underlying \nMedical Conditions \nAuthor, year \nB7471014            \n \n       \n  \n  \n  \n \n \n    \n    \n \n  \n   \n \n    \n    \n \n  \n    \n   \n     \n   \n    \n Study design Intervention Country Age Total \npopulation N Intervention N comparison Outcomes \nFunding \nsource \nSingle dose PCV20 @ 15m to <24m; 15m \nprevious \nvaccination ≥3 to \n<24m 209 209 N/A \nPhase III doses of PCV13 \nImmuno-genicity and \nsafety Pfizer Clinical Trial \nin healthy \nchildren, \nsome previously Single dose PCV20 @ 2y to <5y; previous \nvaccination ≥3 \ndoses of PCV13 US 2y to <5y 216 216 N/A \nvaccinated Single dose PCV20 @ 5y to <10y \nSingle dose PCV20 \n@ 10 to <18y 5y to <10y 201 201 N/A \n55 10y to <18y 205 205 N/A \nGRADE Summary of Findings: PCV20 Use in Children Aged 2–18 Years \nwith Underlying Medical Conditions \nCertainty assessment № of patients Results \nCertainty Importance № of \nstudies Study \ndesign Risk of \nbias Inconsistency Indirectness Imprecision Other \nconsiderations Intervention comparison Relative \n(95% CI) Absolute \n(95% CI) \nVaccine effectiveness            \n   \n   \n      \n  \n \n         \n   \n   \n    \n    \n     11 Non-RCT Very \nSerious \na Not \napplicable Very \nSeriousb,c Not \nserious Not serious 752-75 7 None IgG GMCs were higher 1-\nmonth post-PCV20 dose compared to before vaccination for 13/13 shared serotypes and 7/7 additional serotypes, for all age groups \nVery Low Critical \n                           \n        \n                \n                a. Study design is an open label non-randomized controlled trial with no comparator group. Downgraded for lack of randomization, lack of blinding, and lack of a comparison group. \nb. Study population did not include children with underlying conditions \nc. This is an immunogenicity study and there are no correlates of protection for some critical outcomes considered \nReferences \nB7471014. Safety and Immunogenicity Study of 20vPnC in Healthy Children 15 Months Through 17 Years of Age 56 \nGRADE Summary of Findings: PCV20 use in Children Aged 2–18 \nYears With Underlying Medical Conditions \nCertainty assessment № of patients Results \nCertainty Importance № of \nstudies Study design Risk of \nbias Inconsistency Indirectness Imprecision Other \nconsiderations PCV20 Intervention Relative \n(95% CI) Absolute \n(95% CI) \nSerious Adverse Events (SAEs) following vaccination            \n    \n   \n       \n  \n     \n      \n   11 Non-\nrandomized \ntrial Serious \na Not \napplicable Seriousb Seriousc Not serious 0.6% \n(n=831) No vaccine-related \nSAEs reported Very Low Critical \n            \n        \n           \n                a. Study design is an open label non-randomized controlled trial with no comparator group\nb. Study population did not include children with underlying conditionsc. No vaccine-related serious adverse events reported; relative risk crossing 1\nReference \nB7471014. Safety and Immunogenicity Study of 20vPnC in Healthy Children 15 Months Through 17 Years of Age \n57", "summary": "Nationa  l Center  for  Immunizatio  n &  Respirator  y Diseases                                Evidence to Recommendations Framework (Preliminary):  Use of 20-valent Pneumococcal Conjugate Vaccine in U.S. Children  Miwako Kobayashi, MD, MPH  Pneumococcal Vaccines Work Group  Advisory Committee on Immunization Practices  February 22, 2023                                                                                                                Evidence to Recommendations (EtR) framework …", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/Pneumococcal-05-Kobayashi-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 57}
{"title": "01 RSV Mat Peds Long 508", "content": "Maternal/Pediatric Respiratory Syncytial Virus (RSV) \nWork Group​\nSarah S. Long, MD\nChair, Maternal/Pediatric RSV Work Group\nACIP Meeting\nJune 28, 2024National Center for Immunization and Respiratory Diseases \n\n•RSV prevention in infants during their first RSV season (i.e., aged <8 months)\n-To protect infants in their first season , either maternal RSV vaccination ( Abrysvo , \nPfizer), or use of nirsevimab (Beyfortus , Sanofi and AstraZeneca) in the infant is \nrecommended to prevent RSV lower respiratory tract disease\n-Administration of both products is not needed for most infants\n•Children ages 8 –19 months who are at increased risk of severe RSV disease and \nentering their second RSV season are recommended to receive one dose of \nnirsevimabTwo products are recommended to protect infants and \nyoung children from RSV lower respiratory tract disease\nhttps://www.cdc.gov/mmwr/volumes/72/wr/mm7234a4.htm\nhttps://www.cdc.gov/mmwr/volumes/72/wr/mm7241e1.htm  2\nTiming of RSV vaccine  and nirsevimab\nFigure represents recommended timing of immunization product deployment for most of the continental U.S. In jurisdictions with \nseasonality that differs from most of the continental United States (e.g., Alaska, jurisdictions with tropical climates), pro viders should \nfollow state, local, or territorial guidance on timing of administration\n Mother can get RSV vaccine \n(Abrysvo) during pregnancy\nInfant can get RSV antibody \n(nirsevimab) after birth\n•Maternal RSV vaccine\n-For pregnant people at 32 –36 weeks’ gestation, vaccinate using seasonal administration \n(meaning September –January in most of the United States)\n•Nirsevimab1\n-For infants <8 months of age, immunize shortly before season onset (e.g., October)\n-Forinfants born during October –March , immunize within 1 week of birthTiming of administration of maternal Pfizer RSV vaccine (Abrysvo) \nand nirsevimab (Beyfortus) \nhttps://www.cdc.gov/mmwr/volumes/72/wr/mm7234a4.htm; https://www.cdc.gov/mmwr/volumes/72/wr/mm7241e1.htm\n1In jurisdictions with seasonality that differs from most of the continental United States (e.g., Alaska, jurisdictions with t ropical climates), providers should follow state, local, or \nterritorial guidance on timing of administration\n  3\n•Multiple products introduced in the same season \ncreated confusion among healthcare workers as to \nwhich groups were eligible for which immunizations\n•Rare reports of administration errors were received \nby the Vaccine Adverse Events Reporting System \n(VAERS)\n-Reports of pregnant persons receiving Arexvy  \n(GSK’s vaccine for older adults) \n-Reports of children receiving RSV vaccine instead \nof monoclonal antibody products (e.g., \nnirsevimab )\n-Wrong dose ( nirsevimab ) administered\n•CDC made additional resources available and \nincreased education efforts with healthcare \nprovidersVaccine administration errors reported in young \nchildren and pregnant people\nInformation on Respiratory Syncytial Virus (RSV) Vaccine Administration \nErrors in Young Children and Pregnant People\nAdministration of the GSK Respiratory Syncytial Virus Vaccine to Pregnant \nPersons in Error - PubMed (nih.gov)\nIncorrect Administration of Adult RSV Vaccines to Young Children - PubMed \n(nih.gov)5\n\nWork group members (external)\nACIP Members\nSarah Long (chair)\nOliver Brooks\nCamille Kotton\nDenise JamiesonConsultants\nCody Meissner (Dartmouth Geisel School of Medicine)\nHelen Chu (University of Washington)\nNatasha Halasa (Vanderbilt University)\nDaniel Feikin  (World Health Organization)\nKevin Ault (Western Michigan University)\nPablo Sanchez (Nationwide Children’s Hospital)\nLiaisons\nJames McAuley (IDSA)\nBrenna L. Hughes (ACOG)\nNicole Chaisson  (AAFP)\nSean O’Leary (AAP)\nJennifer Schuster (PIDS)\nMolly Howell (AIM)\nDana DeShon  (NAPNAP)GRADE/ EtRConsultants\nDoug Campos -Outcalt\nRebecca MorganEx Officio Members\nLucia Lee (FDA -CBER)\nJudy Beeler (FDA -CBER)\nYodit Belew (FDA -CDER)\nYugenia Hong -Nguyen (FDA -CDER)\nSonnie Kim (NIH -NIAID)\nApril Killikelly (Public Health Agency of Canada)\nWinnie Siu (Public Health Agency of Canada)\nJessica Lee (CMS/CMCS)\nT erry Dalle -T ezze (HRSA)\nMatthew Clark (IHS)\n6\nWork group members (CDC)\nAmber Winn\nChris Taylor\nTami Skoff\nAngie Campbell\nMichael Melgar\nAmanda Payne\nNoelle Molinari\nClaire Midgley\nFiona Havers\nPragna  Patel\nAmadea BrittonRuth Link -Gelles\nMegan Wallace\nMonica Godfrey\nKaren Broder\nNaomi T epper\nHeidi Moline\nHannah Rosenblum\nDerrell Powers\nRaigan Wheeler\nSally Ezra\nManisha PatelCDC ACIP Staff\nMelinda Wharton\nStephanie Thomas\nJessica MacNeilDemorah  Hayes\nElizabeth Greene\nMonica Patton\nJarrett Gartin\nDennis Wang\nJordan Singleton\nTrang Nguyen Wisard\nFatimah Dawood\nJohn Su\nMichael McNeilCDC\nKatherine Fleming -Dutra (co -lead)\nJefferson Jones (co -lead)\nDanielle Moulia\nMeredith McMorrow\nMila Prill\nNatalie Thornburg\nAron Hall\nIsmael Ortega -Sanchez\nMelissa Coughlin\nJamison Pike\nLauren RoperA. Patricia Wodi\nChristine Olson\nAnne Hause\nAndrew Leidner\nDavid Shay\nSarah Meyer\nKristen Folsom\nJulianne Gee\nAgustin Lopez\nLakshmi Panagiotakopoulos\n7\n•Implementation and uptake of nirsevimab  and maternal RSV vaccine — Dr. \nShannon Stokley (CDC/NCIRD) \n•Maternal RSV vaccine safety surveillance — Dr. Pedro Moro (CDC/NCEZID) \n•Summary of effectiveness of nirsevimab  in infants — Dr. Amanda Payne \n(CDC/NCIRD) \n•Work Group considerations — Dr. Jefferson Jones (CDC/NCIRD)Agenda\n8\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position \nof the U.S. Centers for Disease Control and Prevention.\nThank you", "summary": "Maternal/Pediatric Respiratory Syncytial Virus (RSV)  Work Group​ Sarah S. Long, MD Chair, Maternal/Pediatric RSV Work Group ACIP Meeting June 28, 2024National Center for Immunization and Respiratory Diseases   •RSV prevention in infants during their first RSV season (i.e., aged <8 months) -To protect infants in their first season , either maternal RSV vaccination ( Abrysvo ,  Pfizer), or use of nirsevimab (Beyfortus , Sanofi and AstraZeneca) in the infant is  recommended to prevent RSV lower…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/01-RSV-Mat-Peds-Long-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 9}
{"title": "02 RSV Mat Peds Stokley 508", "content": "Implementation and Uptake of Nirsevimab and \nMaternal Vaccine\nShannon Stokley, DrPH\nDeputy Director for Science Implementation\nImmunization Services Division\nNational Center for Immunizations and Respiratory Diseases (NCIRD)\nJune 2024National Center for Immunization and Respiratory Diseases\n\n2023 -2024 Coverage for Nirsevimab and \nMaternal Vaccination\nPercent of pregnant persons ages 18 –49 years vaccinated with RSV vaccine \noverall and by race and ethnicity, Vaccine Safety Datalink\n•17.8% of pregnant persons vaccinated overall\n•Vaccination coverage ranged from 10.3% among Black pregnant persons \nto 24.8% among Asian pregnant persons\nData source: https://www.cdc.gov/vaccines/imz -managers/coverage/rsvvaxview/pregnant -persons -coverage -intent.html  \nMonthly nirsevimab  receipt and intent among women ages 18 –49 years who \nhave an infant <8 months, National Immunization Survey -Adult COVID \nModule (NIS -ACM)\n13.520.628.740.5 43.0 41.340.0 26.931.421.7 16.7 22.835.7 47.330.131.530.024.310.95.29.86.310.3 11.6\n0102030405060708090100\nOct-23 Nov-23 Dec-23 Jan-24 Feb-24 Mar-24Percent\nData source: https://www.cdc.gov/vaccines/imz -managers/coverage/rsvvaxview/nirsevimab -coverage.html  \n•51.2% of infants are estimated to be protected from RSV by either receipt of nirsevimab  or maternal RSV \nvaccination.\n•Infants eligible for nirsevimab : 3,900,000\n-Those 0 –7 months old during October 2023 –March 2024\n-Born March 2023 –March 2024\n-Assume 300,000 babies born each month\n-43.0%  received nirsevimab  (from  February  NIS-ACM)\n•Infants eligible for protection by maternal vaccination (a subset of infants eligible for nirsevimab ): 1,800,000\n-Born October 2023 –March 2024\n-Born to mot hers 32 -36 weeks' gestation and eligible for RSV vaccination September 2023 –January 2024\n-17.8%  of mothers  received RSV vaccination (from VSD data through January 2024)\n•Estimated number of infants who received nirsevimab  = .430*3,900,000 = 1,677,000\n•Estimated number of infants protect by maternal RSV vaccination = .178*1,800,000 = 320,400\n•Percent protected by either = 1,677,000 + 320,400 / 3,900,000 = 51.2%Proportion of infants protected from RSV by receipt of nirsevimab  or \nmaternal RSV vaccination\nData sources: https://www.cdc.gov/vaccines/imz -managers/coverage/rsvvaxview/nirsevimab -coverage.html , https://www.cdc.gov/vaccines/imz -\nmanagers/coverage/rsvvaxview/pregnant -persons -coverage -intent.html , https://wonder.cdc.gov/   \n•IQVIA* data:\n-Among women ages 18 -49 years in the U.S., during September 30, 2023, through April 20, 2024:\n•A total of 223,466 projected RSV vaccine doses were administered\n–96,611 (43%) in physician medical offices**. Using a sample of 2,866 office -based physicians, \nvaccinations are projected to the ~700,000 office -based physicians in the U.S.\n–126,865 (57%) in U.S. retail pharmacies. Using a sample of 40,469 pharmacies , vaccinations \nare projected to  the ~57,000 pharmacies  in the U.S .\n•NIS-ACM:\n-National survey data\n-Among 1,483 pregnant women <50 years surveyed between December 2023 -March 2024, \n80(5.4%) had already received the RSV vaccine\n•15% in a pharmacy or drug store\n•85% in a medical office (doctor’s office/clinic/hospital/health dept)Location of Maternal RSV Vaccine Administration\n*Data sources: Immunization Services Division’s custom IQVIA Longitudinal Prescription Claims ( LRx) + Medical Claims (Dx) data files (delivery date April 20, \n2024).  ** The projection to office -based physicians uses a list of US licensed office -based MDs and DOs maintained by the AMA. \n•IQVIA data limitations\n-May not be representative\n•Uninsured pregnant people are not represented in medical office estimates.\n•Projected physician medical office estimates are based on a small sample of physicians.\n•Data do not include vaccinations administered at other medical settings such as public health clinics \nand other settings including workplaces and community locations.\n-There is no pregnancy variable in these IQVIA data\n•Estimates include women of reproductive age who received an RSV vaccine during September \n2023 –January 2024. This could include women who were not pregnant when vaccinated or were \npregnant but vaccinated outside the recommended 32 -36 weeks gestation period.\n•NIS-ACM data limitations:\n-Small sample size\n-Gestational age at the time of vaccination is unknown\n•Pregnancy status at time of interview was known, but not gestational age; only some of those \nidentified as pregnant would have been eligible for RSV vaccine at 32 -36 weeks gestation during the \nSeptember -January window for maternal RSV vaccination in most of the U.S. (e.g., in each month, \nmany would have been at <32 weeks gestation when interviewed)Location of Maternal RSV Vaccine Administration: Limitations\nImplementation\nProspective 2024 RSV immunization timeline\nAug Sep Oct Nov Dec Jan\nMaternal RSV vaccination \nresumes in most of continental \nU.S. (9/1)Nirsevimab  administration resumes in most of continental U.S.; broad \navailability (10/1)Limited availability \nof nirsevimab  (9/1)\n•New  immunization products\n•Licensure/launch occurred in \nAug/Sep, which prevented planning  \nin advance of the season\n•Complex  clinical recommendations, \nnuanced communications\n•Lack of awareness  among \nhealthcare providers\n•Challenging have provider/patient \nconversations about vaccination in \nthe context of nirsevimab  shortages•Cost and reimbursement  issues \nduring the first year\n•Access  issues —lack of supply at \nmany OBGYN offices, denial at \npharmacies, requirement of \nprescription\n•Lack of data on coadministration\n•No ability to link maternal and infant \nimmunization records\n•Concerns about safety, efficacyChallenges with maternal RSV vaccination during the 2023 -2024 season\n•There is no anticipated supply/demand mismatch.\n•The Pfizer RSV vaccine is already available in the field.\n-However, providers who will vaccinate only pregnant persons may need to \nrebuild inventory for the 2024 -2025 season.\n-Plans are to have vaccine available for administration September 2024 –January \n2025 for most of the U.S.Maternal vaccine supply for the 2024 -2025 season\nCDC Campaign: From Me, To You\n\n•Timing of policy decision\n-FDA licensure (July 17) of nirsevimab  required special session of ACIP (August 3) leaving <2 months for distribution and roll out \nplanning for October 1 launch\n-Limited time for engagement with key stakeholders and implementing partners to ensure healthcare workers were aware of new \nproduct recommendations and could start procurement processes\n•Procurement and insurance coverage\n-Vaccines for Children (VFC) procurement expedited to ensure availability of nirsevimab  for eligible infants and young children (~50% \nof US children); maternal vaccine for eligible pregnant people aged <19 years\n-Healthcare providers were uncertain of need/demand given that private insurance companies have 12 months to adopt ACIP -\nendorsed vaccine recommendations\n-Demand was strong from parents of young children, many of whom were willing to pay for nirsevimab /vaccine if insurance would not \ncover \n-Nirsevimab  orders exceeded anticipated demand rapidlyChallenges in initial implementation of nirsevimab  \ntargeting infants during the 2023 -2024 season\n•Limited supply of nirsevimab  (100mg and 50mg \nformulations) meant clinicians were uncertain \nhow to ration or prioritize few available doses\n•CDC issued an official Health Advisory notice via \nthe Health Alert Network to prioritize available \ndoses to high -risk infants and younger infants\n•By January, demand had decreased and \nadditional supply was available allowing return \nto original recommendationsInsufficient supply of nirsevimab  to meet demand in \n2023 -2024 season\nHealth Alert Network (HAN) - 00499 | Limited Availability of Nirsevimab  in the United States —Interim CDC Recommendations to Protect \nInfants from Respiratory Syncytial Virus (RSV) during the 2023 –2024 Respiratory Virus Season\n\n•National shortage during 2023 -24 due to faulty assumptions about uptake, presentation mix\n•Manufacturer supply plan for 2024 -25 is focused on\n-Increased volume of product\n-Frontloading of supply\n-Revised mix of presentations\n•Requirements of supply plan include significant logistical actions, regulatory input and \napprovals, careful risk management\n•Limited availability beginning early Sep, ramping up during Sep, broadly available by Oct 1\n•Broadly available supply essential to promote confidence in vaccines/vaccine supply \nand  program implementation\n•Promoting vaccination prior  to broadly available supply risks confusion, disappointment, and \ndecreased confidence among providers and the publicNirsevimab  supply for the 2024 -2025 season\nBirthing Hospital Enrollment into VFC: Strategy\n291 291 293307332348 351 355 359 364 367\n050100150200250300350400\nJuly 2023 Aug 2023 Sept 2023 Oct 2023 Nov 2023 Dec 2023 Jan 2024 Feb 2024 Mar 2024 Apr 2024 May 2024\n(2)Birthing Facilities Enrolled in VFC: August 2023 - May 2024\nBirthing Facilities Enrolled in VFC: August 2023- May 2024\nLinear (Birthing Facilities Enrolled in VFC: August 2023- May 2024)\n(1) These newly enrolled provider counts include 7 providers who were previously enrolled in the VFC program.\n(2) Data for May 2024 is through May 8, 2024.\n•Engaging in data gathering activities:\n-Held series of focus groups to identify facilitators and barriers to enrolling hospitals in VFC\n-National survey of birthing hospitals\n-Mapping hospitals by number of VFC -eligible births, VFC enrollment, and nirsevimab  administration \nhistory\n•Planned activities to scale -up enrollment:\n-Disseminating promising practices and success stories\n-Development of “Promising Practices” FAQ document\n-Working closely with immunization awardees to track process and provide support\n•Implementing activities to reduce enrollment burden:\n-Awardees can enroll birthing hospitals as “specialty providers”; this allows birthing hospitals to offer only \nnirsevimab  and HepB  vaccination birth dose\n•Collaborating with partnersActivities to Increase Hospital VFC Enrollment\nFor more information, contact CDC/ATSDR\n1-800-CDC -INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov           www.atsdr .cdc.gov \nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention and the Agency for Toxic Substances and Disease Registry.\nClosing Slide / Disclaimer", "summary": "Implementation and Uptake of Nirsevimab and  Maternal Vaccine Shannon Stokley, DrPH Deputy Director for Science Implementation Immunization Services Division National Center for Immunizations and Respiratory Diseases (NCIRD) June 2024National Center for Immunization and Respiratory Diseases  2023 -2024 Coverage for Nirsevimab and  Maternal Vaccination Percent of pregnant persons ages 18 –49 years vaccinated with RSV vaccine  overall and by race and ethnicity, Vaccine Safety Datalink •17.8% of…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/02-RSV-Mat-Peds-Stokley-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 18}
{"title": "03 RSV Mat Peds Moro 508", "content": "Pedro L. Moro, MD, MPH \nDivision of Healthcare Quality Promotion\nCenters for Disease Control and Prevention (CDC)NATIONAL CENTER FOR EMERGING AND ZOONOTIC INFECTIOUS DISEASES\nMaternal RSV vaccine safety surveillance\nAdvisory Committee on Immunization Practices (ACIP)\nJune 28, 2024\n▪The findings and conclusions in this presentation are those of the author \nand do not necessarily represent the official position of the CDC\n▪The use of product trade names is for identification purposes onlyDisclaimer\n2\n▪Background\n▪CDC vaccine safety monitoring for Pfizer RSV vaccines in pregnancy:\n•Vaccine Adverse Event Reporting System (VAERS)\n•V-Safe\n•Vaccine Safety Datalink (VSD)\n▪SummaryTopics\n3\n▪In clinical trials among pregnant persons at 24 –36 weeks’ gestation, more preterm births were noted \namong Pfizer RSV vaccine recipients compared to placebo (differences not statistically significant)\n▪Post -licensure safety surveillance of the Pfizer RSV vaccine in pregnant persons was initiated during \nthe 2023 -2024 season\n▪The patterns of reported local and systemic (e.g., headache) symptoms in V -safe and VAERS after \nmaternal P fizer RSV vaccine were consistent with its pre -licensure safety profile \n▪Among reports received in VAERS after maternal Pfizer RSV vaccine, the most frequent adverse \nevents reported were p regnancy -specific conditions (e.g., preterm delivery) , as expected for a vaccine \nrecommended at 32 -36 weeks’ gestational age\n▪Preliminary findings in the VSD observed that the incidence of preterm births is 4.1% among pregnant \npersons who received Pfizer RSV vaccine during the 2023 -2024 respiratory season. This was within \nthe expected range of the incidence of preterm births at 32 -36 weeks’ gestation (3.1 - 6.1%) before \nintroduction of this vaccine\n▪CDC and FDA will continue to monitor maternal RSV vaccine safety in VAERS, V-safe and VSDKey points up front\n4\n▪In clinical trials among pregnant persons at 24 –36 weeks’ gestation, more preterm \nbirths were noted among Pfizer RSV vaccine recipients compared to placebo, but the \ndifferences were not statistically significant\n•To avoid the potential risk of preterm birth before 32 weeks’ gestation, FDA approved the \nmaternal Pfizer RSV vaccine ( Abrysvo ) for use in pregnant persons at 32 through 36 weeks’ \ngestational age1\n▪The label for Pfizer RSV vaccine notes potential risk of preterm birth under warnings \nand precautions section1\n▪In addition, more hypertensive disorders of pregnancy were observed among vaccine \nrecipients compared to placebo recipients, but the differences were not statistically \nsignificant\n▪Post -licensure safety surveillance of the new Pfizer RSV vaccine in pregnant persons is \nof great importance to ensure maternal Pfizer RSV safety at the population level and \nthe benefits of using the vaccine in pregnant persons to protect infants from RSV LRTD \noutweigh possible risksBackground\nRSV: respiratory syncytial virus; LRTD: lower respiratory tract disease \n1  https://www.fda.gov/media/168889/download  5\nVAERS is the nation’s early warning system for vaccine safety\nCo-managed by \nCDC and FDA\nhttps://vaers.hhs.gov/\n6\nVAERS ADVERSE EVENT REPORTING SYSTEM (VAERS)\nStrengths\n▪National data\n▪Accepts reports from anyone\n▪Rapidly detects safety signals\n▪Can detect rare adverse events\n▪Data available to publicLimitations\n▪Reporting bias\n▪Inconsistent data quality and\ncompleteness\n▪Lack of unvaccinated comparison\ngroup\n▪Generally cannot assess causality\n•VAERS accepts all reports from all reporters without making judgments on\ncausality or judging clinical seriousness of the event\n•As a hypothesis generating system, VAERS identifies potential vaccine safety\nconcerns that can be studied in more robust data systems7\nApproaches to analyzing VAERS data\n▪For more than a decade VAERS has been used as part of vaccine safety surveillance \nfor vaccines used in pregnancy (e.g., influenza, Tdap, COVID -19)1,2\n• Descriptive analysis \n•Clinical review of individual reports \n•Aggregate descriptions of automated data (e.g., counts of reported adverse \nevents)\n•Calculation of reporting rates for pregnancy outcomes (if doses of a vaccine \nadministered in pregnancy or vaccination coverage data are available)\n▪Clinical review of infant’s medical records at birth and for the first 3 months of life \n(enhanced surveillance)\n1Moro et al.  Obstetrics & Gynecology 140(3):p 421 -427, September 2022. https://journals.lww.com/greenjournal/Fulltext/2022/09000/Safety_of_Booster_Doses_of_Coronavirus_Disease.11.aspx\n2Moro et al. Vaccine. 34(20):p2349 -2353, April 2016. https://www.sciencedirect.com/science/article/pii/S0264410X16300329?via%3Dihub 8\nCharacteristics of maternal Pfizer RSV vaccine reports submitted to VAERS \n(as of June 3, 2024)\nCharacteristics N (%)\nNumber of reports 121\nMaternal deaths 0\nPregnancy -specific adverse event(s) reports 52 (43)\nMaternal age in years, median (range) 1 32 (21 -41)\nMaternal age ≥ 35 years 24 (20)\nOnset interval in days from vaccination to adverse event, median (interquartile range) 1 (0,4)\nGestational age2 in weeks at time of vaccination, median (range) 34 (9,37)\nType of reporter\nPatient/relative3 60 (50)\nProvider 36 (30)\nVaccine manufacturer 19 (16)\nOther 6 (5)\n1 Age not provided in 15 reports; 2 Gestational age at vaccination available for 90 reports; unknown for 31 reports \n3 Pregnant persons represented 70% of those who reported a preterm delivery   \nFrom October 2023 through March 2024 an estimated 320,400 pregnant persons received RSV vaccine (Peacock. Implementation and Uptake of Nirsevimab  and Maternal RSV Vaccine. \nAdvisory Committee on Immunization Practices. June 28, 2024.9\nMost frequently reported MedDRA Preferred Terms1 among reports (n=121) \nto VAERS following Pfizer RSV vaccination in pregnant persons (as of June 3, \n2024)\nRank MedDRA PT (not mutually exclusive) N (%)\n1 Premature delivery 29 (24)\n2 Premature labor 18 (15)\n3 Caesarean section 18 (15)\n4 Uterine contractions during pregnancy 16 (13)\n5 Headache 15 (12)\n6 Nausea 13 (11)\n7 Fever 13 (11)\n8 Vomiting 12 (10)\n9 Pain 11 (9)\n10 Preterm premature rupture of membranes 10 (8)\n1 Medical Dictionary for Regulatory Activities Preferred Terms ( https://www.meddra.org/how -to-use/basics/hierarchy ); MedDRA PTs not mutually exclusive\nFrom October 2023 through March 2024, an estimated 320,400 pregnant persons received RSV vaccine (Peacock. Implementation and  Uptake of Nirsevimab  and \nMaternal RSV Vaccine. Advisory Committee on Immunization Practices. June 28, 2024.10\nAdverse events among pregnant persons following Pfizer RSV vaccination in VAERS \n(as of June 3, 2024)\nAdverse event N (%)\nPregnancy specific 52 (43)\n Premature delivery (< 37 weeks' gestation) 37 (31)\n High blood pressure/gestational hypertension1 4 (3)\n Infant death2 1 (1)\n Stillbirth  (≥ 20 weeks' gestation) 3 (2)\n Delivery/labor/contractions 3 (2)\n Premature rupture of membranes 2 (2)\n Other3 2 (2)\nNon -pregnancy specific 69 (57)\n General disorders and administration site conditions\n (mostly injection site and systemic reactions)41 (34)\n Vaccination errors4 21 (17)\n Infections and infestations 3 (2)\n Neurological disorders (Bell’s palsy)6 2 (2)\n Other4 5 (4)\n1  One report of thrombocytopenia that met Brighton level 2 criteria was reported in a patient with elevated blood pressure foll owing vaccination\n2 35-week infant with anoxic brain injury and neonatal death after emergent C -section, resuscitation, and hospital transfer 4 days  after vaccination\n3 Other includes one report each of premature infant incorrectly classified as preterm (37w), a patient who underwent labor at 37 weeks, 6 days\n4  Vaccination errors included: eight reports of vaccine given outside recommended gestational period, six given outside season,  three reports \n   of an additional dose of RSV given during same season, before approval in two, subcutaneous route in one, storage issue for \n   Covid -19 vaccine, not RSV. Three reports of adverse events with vaccination errors  \n5 Other includes two reports of no adverse event, and one each of diarrhea, infant with jaundice, and a report of rash\nFrom October 2023 through March 2024, an estimated 320,400 pregnant persons received RSV vaccine (Peacock. Implementation \nand Uptake of Nirsevimab  and Maternal RSV Vaccine. Advisory Committee on Immunization Practices. June 28, 2024.\n6 No verified cases of Guillain -Barre Syndrome reported11\n12Preterm deliveries (as of June 3, 2024)\nRisk factors and clinical information2\n▪ 22 reported a medical condition or \ncomplication that increased risk for preterm \ndelivery (e.g., elevated blood pressure, history \nof preterm delivery)\n▪ 12 had insufficient information (no medical \nrecords)\n▪ 3 uncomplicated pregnancies (no reported \nfactors)\n▪ 8 deliveries were inducedClassification1N\nLate preterm (34 -36 weeks) 27\nEarly preterm (≥ 32 - <34 weeks) 7\nVery preterm (28 - < 32 weeks) 0\nExtremely preterm (< 28 weeks) 0\nUnknown gestational age 3\nTotal 37**\n1 Based on ACOG and WHO definitions\n2 Median maternal age at vaccination was 33 years (range 25 -40 years); median onset interval from vaccination to preterm birth \nwas 3 days (range 0 -31 days) \nFrom October 2023 through March 2024, an estimated 320,400 pregnant persons received RSV vaccine (Peacock. \nImplementation and Uptake of Nirsevimab  and Maternal RSV Vaccine. Advisory Committee on Immunization Practices. June 28, 2024 .\n13Characteristics and outcomes of infants born to Pfizer RSV recipients\nCharacteristics N (%)\nNumber of infants175\nPremature at birth (< 37 weeks)238 (51)\nGestational age at birth (weeks) 3, median (range) 36 (32 – 41)\nInfants at term 33 (44)\nSex\n Male 32 (43)\n Female 34 (45)\n Unknown sex 9 (12)\nInfant deaths41\nInfant born with low birth weight (< 2,500 g) 16 (21)\nNICU admission524\n Condition or reason for admission in NICU (not mutually exclusive)\n Respiratory distress\n Prematurity\n Fetal distress\n Unknown10 (42)\n7 (29)\n1 (4)\n9 (38)\n1 66 infants born of a single pregnancy; 6 from 3 twin pregnancies; 3 data not reported\n2 Includes 6 infants from three twin pregnancies\n3 Gestational age at birth unknown for 4 reports\n4 35-week infant with anoxic brain injury and neonatal death after emergent C -section, resuscitation, and hospital transfer 4 day s after vaccination\n5 NICU admission unknown in 20 (39%) reports\nFrom October 2023 through March 2024, an estimated 320,400 pregnant persons received RSV vaccine (Peacock. Implementation \nand Uptake of Nirsevimab  and Maternal RSV Vaccine. Advisory Committee on Immunization Practices. June 28, 2024.\n▪Among reports received, local and systemic symptoms (e.g., headache) were   \nfrequently reported in VAERS after Pfizer RSV vaccine consistent with pre -licensure \nstudies in pregnant persons\n▪In clinical trials among pregnant persons at 24 –36 weeks’ gestation, more preterm \nbirths were noted among Pfizer RSV vaccine recipients compared to placebo\n▪The label for Pfizer RSV vaccine notes potential risk of preterm birth under warnings \nand precautions section\n▪Patients (pregnant persons) were the most common reporters (50%) overall and \nrepresented 70% of those who reported a preterm delivery \n▪Reports of pregnancy specific conditions (e.g., preterm delivery) were not \nunexpected for the Pfizer RSV vaccine, which is recommended at 32 -36 weeks’ \ngestation in pregnancyVAERS Summary\n14\nV-safe\n15\n▪Surveys sent daily during the first week after vaccination, then weekly through week 6\n▪Daily surveys solicit adverse events and health impacts after vaccination\n•Local  reactions (e.g., pain, redness, swelling)\n•Systemic reactions (e.g., fatigue, headache, muscle pain)\n•Health impacts (e.g., unable to perform normal daily activities, missed school or \nwork, or received medical care)\n•Additional questions for persons who reported immunocompromise at vaccination\n▪Weekly surveys solicit new symptoms or conditions after vaccination\n▪Maternal RSV protocol includes additional questions about current and prior \npregnanciesIn Fall 2023 V-safe expanded to include RSV vaccine\n16\nCharacteristics of persons aged 16 -49 years with \nreported RSV vaccination during pregnancy*\n* For 1,116 V -safe participants aged 16 -49 years enrolled in the maternal RSV protocol with ≥1 completed daily survey during Aug ust 21, 2023 – May 20, \n202417\nReactions and health impacts reported for persons aged 16 -49 \nyears with reported RSV vaccination during pregnancy (n=1,116)*\n0102030405060708090100\nAny symptoms Injection site\nreactionSystemic reaction Unable to complete\ndaily activitiesUnable to work or\nattend schoolGot medical care\nPfizer\n* For 1,116 V -safe participants aged 16 -49 years enrolled in the maternal RSV protocol with ≥1 completed daily survey \nduring August 21, 2023 – May 20, 202418\nVaccine Safety Datalink\n19\nVaccine Safety Datalink (VSD) 2024\n▪Collaborative project between CDC and \nintegrated healthcare organizations\n▪Monitors safety of vaccines used in the \nUS, primarily through real -world data of \nrare and serious events following \nvaccination\n▪Includes data on ~15.5 million \nindividuals across all sites annually\n▪~ 115,000 annual live births\n▪Data is organized using a common data \nmodel with standardized coding \nsystems\n20\n▪Determine cumulative historical  incidence rates of preterm birth among \nsingleton pregnancies in the VSD reaching specified gestational ages from \n22–36 weeks during 2017 –2022\n▪Determine incidence of preterm births in RSV vaccinated pregnant \npersons1,2VSD Prenatal RSV Vaccine Surveillance\n1For RSV vaccines administered at 30 to less than 37 weeks’ gestation \n2Pfizer RSV should be administered at 32 through 36 weeks’ gestation \nhttps://www.fda.gov/media/168889/download21\nPreterm births in VSD – Historical incidence of preterm births and preterm \nbirths following RSV vaccine during pregnancy at 9 VSD sites \nIncidence of preterm births among singleton pregnancies in the VSD reaching \nspecified gestational ages from 22 –36 weeks during 2017 –2022\n▪In VSD, 10,295 RSV vaccines were administered at 30 to less than 37 weeks gestational age among\npregnant persons during 2023 –2024 respiratory season with 427 preterm births among vaccinees.\n▪The preterm birth incidence was 4.1% which is within the expected range (3.1–6.1%) based on\nhistorical data.\n22\n▪Pregnant persons, RSV vaccinated: unexposed at same gestational week \n▪Create propensity scores to account for confounding\n▪Outcomes\n•Acute safety outcomes (e.g., anaphylaxis, Guillain -Barré syndrome)\n•Preterm birth\n•Stillbirth\n•Preeclampsia/eclampsia/HELLP* \n▪2023 -2024 analysis pending, data available later this yearVSD 1:1 Matched analysis (ongoing)1\n*Hemolysis, elevated liver enzymes, low platelet count\n1https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2023 -09-22/02 -Mat-Peds -DeSilva -508.pdf  23\n▪Local and systemic symptoms were reported to V -safe following Pfizer RSV vaccine in \npregnant persons, with a frequency similar to that observed in pre -licensure trials; \nfew pregnant people in V -safe reported medical care for symptoms1 \n▪Among reports received in VAERS after maternal Pfizer RSV vaccine, the most \nfrequent adverse events reported were local and systemic symptoms (e.g., headache) \nand pregnancy specific conditions (e.g., preterm delivery), as expected for a vaccine \nrecommended for pregnant persons at 32 -36 weeks’ gestation\n▪Post -licensure vaccine safety data from VAERS and V -safe during first season after \nmaternal Pfizer RSV vaccine are consistent with the pre -licensure safety profile \n▪Preliminary findings in the VSD observed that the incidence of preterm births is 4.1% \namong pregnant persons who received Pfizer RSV vaccine during the 2023 -2024 \nrespiratory season. This was within the expected range of the incidence of preterm \nbirths at 32 -36 weeks’ gestation (3.1 - 6.1%) before introduction of this vaccine\n▪CDC and FDA will continue to monitor maternal RSV vaccine safety in VAERS, V -safe \nand VSDSummary\n24 1 https://www.fda.gov/vaccines -blood -biologics/abrysvo  \nAcknowledgements\n▪CDC Immunization Safety Office\n•VAERS Team\n•V-safe Team\n•Clinical Immunization Safety Assessment (CISA) Project\n•Vaccine Safety Datalink (VSD)\n▪Food and Drug Administration\n•Office of Biostatistics and Pharmacovigilance, Center for Biologics Evaluation and \nResearch\n▪National Center for Immunization and Respiratory Diseases\n•Coronavirus and Other Respiratory Viruses Division\n25\nFor more information, contact CDC/ATSDR\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov           www.atsdr.cdc.gov \nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention and the Agency for Toxic Substances and Disease Registry.\nClosing Slide / Disclaimer\nThe findings and conclusions in this presentation are those of the authors \nand not necessarily represent the official position of CDC", "summary": "Pedro L. Moro, MD, MPH  Division of Healthcare Quality Promotion Centers for Disease Control and Prevention (CDC)NATIONAL CENTER FOR EMERGING AND ZOONOTIC INFECTIOUS DISEASES Maternal RSV vaccine safety surveillance Advisory Committee on Immunization Practices (ACIP) June 28, 2024 ▪The findings and conclusions in this presentation are those of the author  and do not necessarily represent the official position of the CDC ▪The use of product trade names is for identification purposes…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/03-RSV-Mat-Peds-Moro-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 26}
{"title": "04 RSV Mat Peds Payne 508", "content": "Summary of effectiveness of nirsevimab  in infants\nAmanda Payne, PhD, MPH\nCoronavirus and Other Respiratory Viruses Division\nCenters for Disease Control and Prevention\nJune 28, 2024National Center for Immunization and Respiratory Diseases\n•Real -world vaccine/product effectiveness methods\n•Effectiveness of nirsevimab  in the United States\n-RSV-associated emergency department encounters & hospitalization, VISION\n-RSV-associated medical encounters and hospitalization, NVSN\n•Effectiveness of nirsevimab  globally\n•ConclusionsAgenda\nReal -world vaccine/product effectiveness \ncontext and methods\n•Efficacy: the degree to which an immunization prevents disease under \nideal and controlled conditions  (i.e., measured in clinical trials)\n•Effectiveness: the degree to which an immunization prevents disease \nunder real -world conditions (i.e., measured in post -licensure observational \nstudies)\nIn this presentation,\nwe’ll discuss product effectiveness (“PE”)\nfrom real -world data.Efficacy ≠ effectiveness\n•Limited supply of nirsevimab  (100mg and 50mg\nformulations) meant clinicians were uncertain\nhow to ration or prioritize few available doses\n•CDC issued an official Health Advisory notice via\nthe Health Alert Network to prioritize available\ndoses to high -risk infants and younger infants\n•By January, demand had decreased and\nadditional supply was available allowing return\nto original recommendationsInsufficient supply of nirsevimab  to meet demand in \n2023 -2024 season\nHealth Alert Network (HAN) - 00499 | Limited Availability of Nirsevimab  in the United States —Interim CDC Recommendations to Protect \nInfants from Respiratory Syncytial Virus (RSV) during the 2023 –2024 Respiratory Virus Season\n\nCase ControlPerson with acute\nrespiratory illness\nRSV test\nRSV immunization\nstatus\nObservational effectiveness measured in a \ntest-negative design (TND) study\nEffectiveness = 1 – (odds ratio ) x 100%    Odds ratio = 𝑂𝑑𝑑𝑠  𝑜𝑓 𝑖𝑚𝑚𝑢𝑛𝑖𝑧𝑎𝑡𝑖𝑜𝑛 𝑐𝑎𝑠𝑒𝑠\n𝑂𝑑𝑑𝑠  𝑜𝑓 𝑖𝑚𝑚𝑢𝑛𝑖𝑧𝑎𝑡𝑖𝑜𝑛 𝑐𝑜𝑛𝑡𝑟𝑜𝑙𝑠Key features of a TND\n•Real -world circumstances\n•Most heterogenous study population,\noften “all comers”\n•Reduces bias from health -care seeking behavior\nConsiderations \n•Validity dependent on test performance\n•Residual confounding is possible\nSlide courtesy of Ruth Link -Gelles, PhD MPH Chua H, Feng S, Lewnard  JA, et al. The use of test -negative controls to monitor vaccine effectiveness: a systematic review of methodology. Epidemiology 2020;31:43 -64.\nVirtual SARS -CoV-2, Influenza, and Other \nrespiratory viruses Network (VISION)\n•Population: Visiting a participating ED for or hospitalized with RSV -like \nillness (RLI)*\n•Immunization data:  Infant and maternal RSV immunization status \ndocumented by electronic health records, state and city registries, and \nclaims data (subset of sites)\n•Covariate data:  Documented in electronic health records\n-Underlying medical conditions:  ICD -10 discharge diagnosis codes at time of \nRLI encounter\n-Patient characteristics\n•Date of birth\n•Census tract of residence\n•SexVISION Multi -Site Network of Electronic Health Records (EHRs)\n127 emergency rooms and 107 hospitals\nVISION 2.0 partners included in this analysis – \nED: Columbia, HealthPartners Institute, Intermountain Healthcare, \nKPSC, KPCHR, Regenstrief\nInpatient : Columbia, HealthPartners Institute, Intermountain, KPSC, \nKPCHR, Regenstrief\n*≥1 ICD -10 discharge diagnosis code indicating RSV -like illness (RLI)\nED = emergency department\nED Encounters and Hospitalizations for RSV -like illness* among infants in their first RSV \nseason, by immunization and RSV positivity status – VISION, October 2023 – March 2024\nED Encounters and Hospitalizations for RSV -like illness* among infants in their first RSV \nseason, by immunization and RSV positivity status – VISION, October 2023 – March 2024\nED Encounters and Hospitalizations for RSV -like illness* among infants in their first RSV \nseason, by immunization and RSV positivity status – VISION, October 2023 – March 2024\nED Encounters and Hospitalizations for RSV -like illness* among infants in their first RSV \nseason, by immunization and RSV positivity status – VISION, October 2023 – March 2024\n•Population:  \n-Infants aged <8 months as of October 1, 2023, or born after October 1, 2023\n-Visiting a participating ED for or hospitalized with RSV -like illness (RLI)\n-With RSV test result within 10 days before or 72 hours after encounter\n•Cases:   RLI with positive  RSV antigen or NAAT test*\n•Controls:   RLI with negative RSV NAAT test\n•Study period:  October 8, 2023 – March 31, 2024\n•Exclusion criteria:\n-Children aged <7 days\n-Children born after September 22, 2023, without linkage to maternal records\n-Evidence of maternal RSV vaccination or palivizumab administration \n-Receipt of unrecommended nirsevimab dose(s)†\n-<7 days between nirsevimab dose and RLI encounter\n-Indeterminate RSV test result\n•Statistical Analysis:  Adjusted OR comparing odds of immunization‡ among cases vs. controls estimated \nusing  multivariable logistic regression models, adjusting for age, race and ethnicity, sex, calendar day (days \nsince Oct 8, 2023), and geographic region → PE = (1 -aOR) X 100%Test-negative design (TND) analysis of first season nirsevimab  product effectiveness (PE) against \nRSV-associated ED encounters and hospitalization – VISION, October 8, 2023 – March 31, 2024\n*RSV -positive encounters with positive SARS -CoV -2 and/or influenza test result were (i.e., coinfections) were excluded.\n† Unrecommended nirsevimab  dose(s) defined as:  nirsevimab doses administered on or before October 1, 2023, and receipt of >1 nirsevimab  dose.  Nirsevimab  doses in older children may be \nadministered as 2 injections on the same day; this was considered one ‘dose’.\n‡Immunization defined as one nirsevimab  dose ≥7 days prior to encounter index date.\nNAAT = nucleic acid amplification test | OR = odds ratio | aOR  = adjusted odds ratio | PE = product effectiveness\nFirst season nirsevimab product effectiveness (PE) against RSV-associated ED \nencounters and hospitalization – VISION, October 8, 2023 – March 31, 2024\nOutcome | Nirsevimab  \ndosage patternTotal\nencountersRSV -positive \nencounters\nN (Row %)Median days \nsince dose \n(IQR)Adjusted \nPE (95% CI)*\nRSV -associated ED encounter\nNo nirsevimab  doses4,610 1,988 (43)N/A ref\nNirsevimab , ≥7 days prior 442 63 (14) 53 (27 -84) 77 (69 -83)\nRSV -associated hospitalization\nNo nirsevimab  doses927 601 (65)N/A ref\nNirsevimab , ≥7 days prior 93 4 (4) 48 (25 -84) 98 (95 -99)\n0 20 40 60 80 100\n*Odds ratio used to calculate VE estimate was adjusted for age, race and ethnicity, sex, calendar day (days since Oct 8, 2023), and geographic region\nN/A = not applicable | ref = reference groupNirsevimab was effective against RSV-associated ED encounters and \nhospitalization among infants in their first RSV season.\nNew Vaccine Surveillance Network (NVSN)Update to Moline HL, Tannis  A, Toepfer  AP , et al. Early Estimate of Nirsevimab  Effectiveness for Prevention of Respiratory Syncytial \nVirus –Associated Hospitalization Among Infants Entering Their First Respiratory Syncytial Virus Season — New Vaccine \nSurveillance Network, October 2023 –February 2024. MMWR Morb  Mortal Wkly  Rep 2024;73:209 –214. DOI: \nhttp://dx.doi.org/10.15585/mmwr.mm7309a4  \n\nNVSN is a prospective, population -based surveillance network for \npediatric acute respiratory illness (ARI) at 7 U.S. medical centers.\nChildren <18 years of age with ARI are enrolled \nyear -round in the outpatient, urgent care, \nemergency department (ED), and hospital settings.\nSurveillance Objectives:\n–Determine the etiology and burden of laboratory -\nconfirmed acute viral respiratory diseases in children\n–Characterize the clinical and epidemiologic factors of \npediatric ARI and associated syndromes\n–Evaluate vaccine effectiveness (VE) using a test -\nnegative design (TND) and impact of vaccines and \nother immunoprophylaxis  products.\n\nNVSN Data Collection\n•Caregiver interview\n-Race and ethnicity, preterm status, date of symptom onset, breastfeeding status\n•Specimens\n-Mid-turbinate nasal swab collected from all children for RSV testing by reverse -\ntranscription polymerase chain reaction; results of both clinical and surveillance \ntesting are collected\n-Sequencing of RSV -positive specimens to monitor for substitutions in the \nnirsevimab  binding site\n•Medical chart abstraction\n-Age, underlying medical conditions, clinical course of illness, insurance status\n•Immunization status ( nirsevimab , palivizumab, and maternal RSV vaccine)\n-Ascertained by parent report and confirmed with state immunization information \nsystem, electronic health record, or birth record\n\nDuring 2023 -2024, RSV prevention products became available in the U.S. after \nthe RSV season started\nACIP = Advisory Committee on Immunization Practices \nNVSN = New Vaccine Surveillance Network\nNREVSS = National Respiratory and Enteric Virus Surveillance System Nirsevimab  recommended by  ACIPPfizer maternal RSV vaccine ( Abrysvo ) \nrecommended by ACIP\nAll NVSN sites had some \nnirsevimab availability by \nmid-October\nAmong 2,383 infants in \ntheir first RSV season\n•11.1% received\nnirsevimab\n•2.2% received\npalivizumab\n•3.4% (of 1,542\ninfants <6 months\nof age at\nenrollment) had\nhistory of maternal\nRSV vaccination, April 2023 through April 2024\nDuring 2023 -2024, RSV prevention products became available in the U.S. after \nthe RSV season started\nACIP = Advisory Committee on Immunization Practices \nNVSN = New Vaccine Surveillance Network\nNREVSS = National Respiratory and Enteric Virus Surveillance System Nirsevimab  recommended by  ACIPPfizer maternal RSV vaccine ( Abrysvo ) \nrecommended by ACIP\nAll NVSN sites had some \nnirsevimab availability by \nmid-October\nAmong 2,383 infants in \ntheir first RSV season\n•11.1% received\nnirsevimab\n•2.2% received\npalivizumab\n•3.4% (of 1,542\ninfants <6 months\nof age at\nenrollment) had\nhistory of maternal\nRSV vaccination, April 2023 through April 2024\nDuring 2023 -2024, RSV prevention products became available in the U.S. after \nthe RSV season started\nACIP = Advisory Committee on Immunization Practices \nNVSN = New Vaccine Surveillance Network\nNREVSS = National Respiratory and Enteric Virus Surveillance System Nirsevimab  recommended by  ACIPPfizer maternal RSV vaccine ( Abrysvo ) \nrecommended by ACIP\nAll NVSN sites had some \nnirsevimab availability by \nmid-October\nAmong 2,383 infants in \ntheir first RSV season\n•11.1% received \nnirsevimab\n•2.2% received \npalivizumab\n•3.4% (of 1,542 \ninfants <6 months \nof age at \nenrollment) had \nhistory of maternal \nRSV vaccination, April 2023 through April 2024\nTest-negative design (TND) analysis of first season nirsevimab  product effectiveness (PE) against \nmedically attended RSV -associated ARI episodes and RSV -associated hospitalization – NVSN, \nOctober 2023 – March 2024\n*Acute respiratory illness (ARI) defined as  >1 of the following sign/symptoms: fever, cough, earache, nasal congestion, runn y nose, sore throat, vomiting after coughing, shortness of breath (rapid or \nshallow breathing), wheezing, apnea, or apparent life -threatening event or brief resolved unexplained event\n†State -level RSV RT -PCR percent positivity thresholds of 3% were used to define the beginning and end weeks of the analysis by si te\n‡Immunization defined as one nirsevimab  dose ≥7 days prior to symptom onset.\nOR = odds ratio | aOR  = adjusted odds ratio | PE = product effectiveness\n•Population:  \n-Infants <8 months as of October 1, 2023, or born after October 1, 2023 \n-Enrolled from participating medical center\n-ARI*\n•Case patients  – children with medically attended ARI who tested positive for RSV by surveillance or clinical testing\n•Control patients  – children with medically attended ARI who tested negative for RSV by surveillance or clinical testing\n•Study period: October 2023 – March 2024†\n•Exclusion criteria:\n• Chart review incomplete for underlying conditions, preterm status, insurance status, highest level of care, clinical course o f \nillness\n• Immunization status unverified for nirsevimab  and palivizumab receipt and maternal RSV vaccination \n• Receipt of palivizumab or history of maternal RSV vaccination during pregnancy\n• Unknown or inconclusive RSV test result\n• Receipt of nirsevimab  <7 days prior to ARI symptom onset\n•Statistical Analysis:  Adjusted OR comparing odds of immunization‡ among cases vs. controls estimated \nusing  multivariable logistic regression models, adjusting for site, age in months, month of enrollment, and \npresence of >1 high -risk medical condition for severe RSV disease → PE = (1 -aOR) X 100%\nFirst season nirsevimab product effectiveness (PE) against medically attended RSV -\nassociated ARI and RSV -associated hospitalization – NVSN, October 2023 – March 2024*\nOutcome | Nirsevimab  \ndosage patternTotal\nencountersRSV -positive \nencounters\nN (Row %)Median days \nsince dose \n(IQR)Adjusted \nPE (95% CI)†\nMedically Attended\nRSV -associated \nARI episode‡\nNo nirsevimab  doses1,575 755 (48)N/A ref\nNirsevimab, ≥7 days prior§120 9 (8) 42 (21 -73) 89 (77 -94)\nRSV -associated hospitalization\nNo nirsevimab  doses807 526 (65)N/A ref\nNirsevimab , ≥7 days prior 63 6 (10) 38 (15 -67) 91 (79 -96)\n0 20 40 60 80 100\n*State -level RSV RT -PCR percent positivity thresholds of 3% were used to define the beginning and end weeks of the analysis by si te\n†Multivariable logistic regression models compared the odds of vaccination among RSV case and control patients while adjusting  for site, age in months, month of enrollment, and presence of >1 high -risk \nmedical condition for severe RSV disease. \n§Immunization defined as one nirsevimab  dose ≥7 days prior to symptom onset.\nARI = acute respiratory illness | N/A  = not applicable | ref  = reference groupNirsevimab was effective against medically attended RSV -associated ARI \nepisodes and RSV -associated hospitalization.\nSummary of US data\nOutcome/Analysis Vaccine efficacy /effectiveness  (%)\nClinical trial, RSV -associated LRTI 79 (69 -86)\nClinical trial, RSV -associated LTRI with hospitalization 81 (62 -90)\nClinical trial, RSV -associated LRTI with ICU admission 90 (16 -99)\nVISION, RSV -associated emergency department visits 77 (69 -83)\nVISION, RSV -associated hospitalization 98 (95 -99)\nNVSN, medically attended RSV -associated ARI episode 89 (77 -94)\nNVSN, RSV -associated hospitalization 91 (79 -96)Observational data indicate nirsevimab is working as expected \n(vs. RCT results) during the first RSV season after approval \namong infants in their first RSV season\nhttps://www.cdc.gov/mmwr/volumes/72/wr/mm7234a4.htm\nRCT = randomized clinical trial | ARI = acute respiratory illness0 20 40 60 80 100\nResults may not be comparable \nacross studies due to differences in \noutcome definitions, timing, and \nother factors. \n•High product effectiveness should be interpreted with caution\n-Short interval from administration to respiratory illness onset\n-Unable to assess duration of protection during the 2023 -2024 RSV season\n•Residual confounding was possible\n•Misclassification of RSV immunization status was possible\n•These results only reflect PE among infants in their first RSV season (not among \nchildren at increased risk in their second RSV season)\n•VISION:  \n-Cases may have sought care for something other than RSV\n-All RSV testing was clinician -directed\n-EHR data may not fully capture all underlying medical conditions, which may be associated \nwith likelihood of immunization and risk of severe RSV disease\n•NVSN:\n-May not be nationally representativeLimitations of test-negative design (TND) analyses of first season \nnirsevimab  product effectiveness (PE), October 2023 – March 2024\nNirsevimab  effectiveness – evidence from \nliterature\nNirsevimab product effectiveness (PE) among infants in their first RSV season – \nData* from Spain and France\nStudy Endpoint PE (95% CI)†\nRSV -associated hospitalization82 (66 - 90)\n88 (82 - 91)\n89 (70 - 96)\n84 (77 - 90)†\n70 (38 - 89) †\n81 (61 - 91)\nRSV -associated LRTI requiring oxygen87 (69 – 94)\n86 (42 - 96)\nRSV -associated ICU admission90 (76 – 96)\n86 (13 – 98)\n76 (49 – 89)\nRSV and/or bronchiolitis attended in the ED88 (70 – 95)\n55 (48 – 62)\nBronchiolitis or viral pneumonia attended in primary \ncare setting48 (42 – 53)\n61 (24 – 80)\nMedically attended RSV infection69 (52 – 80)\n74 (65 – 80)\n0 20 40 60 80 100\n*References provided on backup slide 32.\n†PE estimates generated from the same study, using different methods.\nLRTI = lower respiratory tract infection | ICU = intensive care unit\nConclusions\n•Nirsevimab was effective against RSV -associated ED encounters and hospitalization \namong infants in their first RSV season during the \n2023 -2024 RSV season\n•Due to timing of authorization/recommendation of RSV prevention products and RSV \nactivity during the 2023 -2024 RSV season:\n-US-based analyses may be subject to residual confounding due to prioritization of nirsevimab \ndoses\n-Short time between nirsevimab administration and outcomes, limiting ability to assess duration of \nprotection\n-Limited ability to assess effectiveness of maternal RSV vaccines\n•Ongoing monitoring of post -licensure nirsevimab and maternal RSV vaccine \neffectiveness will continueConclusions\nAcknowledgements \nCDC\nAmadea Britton\nAllison Ciesla\nBenjamin Clopper\nFatimah S. Dawood\nMonica Dickerson\nKatherine Fleming -Dutra\nSascha Ellington\nShikha Garg\nLeah Goldstein\nCasey Kalman\nAmber Kautz\nRuth Link -Gelles\nJosephine Mak\nErin McKeever\nMeredith McMorrow\nMorgan Najdowski\nLakshmi Panagiotakopoulos\nCaitlin Ray\nAyzsa Tannis\nMark Tenforde\nAriana Toepfer\nMegan Wallace\nRyan WiegandVISION Collaborators\nWestat\nSarah Bell\nSteph Battan -Wraith\nAngela Cheung\nMargaret Dunne\nPatrick Mitchell\nSarah Reese\nElizabeth Rowley\nJanet Watts\nZack Weber\nColumbia University\nKarthik Natarajan\nHealthPartners\nMalini B. DeSilva\nIntermountain Health\nKristin Dascomb\nKaiser Permanente Center for Health Research\nStephanie A. Irving\nKaiser Permanente Southern California\nSara Tartoff\nRegenstrief\nShaun J. Grannis\nUniversity of Colorado\nToan C. Ong\n+ many more site staff!NVSN Collaborators\nCincinnati Children’s Hospital \nMary Staat\nTexas Children’s Hospital \nJulie Boom\nLeila Sahni\nChildren’s Mercy Hospital \nJennifer Schuster\nRangaraj Selvarangan\nVanderbilt University Medical Center\nNatasha Halasa\nUPMC Children’s Hospital \nJohn Williams\nMarian Michaels\nUniversity of Rochester Medical Center\nGeoff Weinberg\nPeter Szilagyi\nSeattle Children’s Hospital \nJan Englund\nEileen Klein\nHospitalized population comparison for VISION and NVSN\nVISION , no. (col %) NVSN , no. (col %)\nCharacteristic Total no. of\npatientsRSV\ncase -patientsRSV\ncontrol -patientsTotal no. of\npatientsRSV\ncase -patientsRSV\ncontrol -patients\nAll hospitalizations 1,020 605 415 870 532 338\nMedian age, months (IQR) 4 (1-7) 3 (1-6) 4 (1-7) 3 (1-6) 3 (1-5) 3 (1-6)\nGestational age\nPreterm (<37 weeks) 133 (13) 59 (10) 74 (18) 180 (21) 102 (19) 78 (23)\nTerm (≥37 weeks) 508 (50) 323 (53) 185 (45) 687 (79) 428 (81) 259 (77)\nUnknown 379 (37) 223 (37) 156 (38) 3 (0) 2 (0) 1 (0)\nRace/ethnicity\nBlack or African American, Non -Hispanic 77 (8) 48 (8) 29 (7) 113 (13) 56 (11) 57 (17)\nWhite, Non -Hispanic 437 (43) 268 (44) 169 (41) 390 (45) 266 (50) 124 (37)\nHispanic or Latino 394 (39) 234 (39) 160 (39) 248 (29) 146 (27) 102 (30)\nOther, Non -Hispanic 75 (7) 33 (6) 42 (10) 107 (12) 58 (11) 49 (14)\nUnknown 37 (4) 22 (4) 15 (4) 12 (1) 6 (1) 6 (2)\nHigh risk conditions for severe RSV disease\nNone 796 (78) 529 (87) 267 (64) 832 (96) 520 (99) 281 (83)\n≥1 224 (22) 76 (13) 148 (36) 38 (4) 12 (2) 26 (8)\nImmunization status\nNo nirsevimab 927 (91) 601 (99) 326 (79) 807 (93) 526 (99) 281 (83)\nNirsevimab , ≥7 days earlier 93 (9) 4 (1) 89 (21) 63 (7) 6 (1) 57 (17)\nEmpirical studies* on nirsevimab product effectiveness (PE) among infants in their first RSV season\nCitation Country Sample Size \n(Number of \nInfants)Study Design PE (95% Confidence Interval)\nAres -Gomez et al., 2024 Spain 10,259 Prospective CohortHospitalization for RSV -related LRTI: 82% (95% CI: 66% - 90%)\nSevere RSV -related LRTI requiring oxygen support: 87% (95% CI: 69% - 94%)\nAll-cause LRTI hospitalizations: 69% (56% - 78%)\nAll-cause hospitalizations:  66% (56% - 74%)\nComa et al., 2024 Spain 26,525Retrospective \nCohortHospital admission for RSV -related disease: 88% (95% CI: 82% - 91%)\nHospital ER visits due to bronchiolitis: 55% (95% CI: 48% - 62%)\nMedically attended RSV infection: 69% (95% CI: 52% - 80%)\nPrimary care attended bronchiolitis: 48% (95% CI: 42% - 53%)\nViral pneumonia diagnosed in primary care: 61% (95% CI: 24% - 80%)\nICU admission for RSV -related disease: 90% (95% CI: 76% - 96%)\nEstrella -Porter et al., 2024 Spain 27,362Retrospective \nCohortMedically attended RSV infection: 74% (95% CI: 65% - 80%)\nEzpeleta et al., 2024 Spain 1,177 Prospective CohortHospitalization due to RSV: 89% (95% CI: 70% - 96%)\nRSV infection attended in the ER: 88% (95% CI: 70% - 95%)\nRSV ICU admission: 86% (95% CI: 13% - 98%)\nLopez -Lacort et al., 2024 Spain 166Screening and Test \nnegative case \ncontrolRSV -LRTI hospital admission (pooled data across several regions):\nScreening methods: 84% (95% CI: 77% - 90%)\nTest negative design: 70% (95% CI: 38% - 89%)\nPaireau  et al., 2024 France 288Test negative case \ncontrolRSV bronchiolitis hospitalized In the pediatric ICU: 76% (95% CI: 49% - 89%)\nAguera  et al., 2024 Spain 181Test negative case \ncontrolHospitalization for RSV -related LRTI:  81% (95% CI:  61% - 91%)\nSevere RSV -related LRTI requiring NIV/CMV:  86% (95% CI:  42% - 96%)\n*Published during June 20, 2023, through June 21, 2024\nLRTI = lower respiratory tract infection | ER = emergency room | ICU = intensive care unit | CI = confidence interval | NIV: noninvasive ventilation | CMV:  continuous mandatory ventilation", "summary": "Summary of effectiveness of nirsevimab  in infants Amanda Payne, PhD, MPH Coronavirus and Other Respiratory Viruses Division Centers for Disease Control and Prevention June 28, 2024National Center for Immunization and Respiratory Diseases •Real -world vaccine/product effectiveness methods •Effectiveness of nirsevimab  in the United States -RSV-associated emergency department encounters & hospitalization, VISION -RSV-associated medical encounters and hospitalization, NVSN •Effectiveness of…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/04-RSV-Mat-Peds-Payne-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 32}
{"title": "05 RSV Mat Peds Jones 508", "content": "Maternal/Pediatric RSV Work Group Considerations\nCDR Jefferson Jones, MD MPH FAAP, USPHS\nCo-lead, Respiratory Syncytial Virus Vaccines – Maternal/Pediatric \nWork Group\nCoronavirus and Other Respiratory Viruses Division\nACIP General Meeting\nJune 28, 2024National Center for Immunization and Respiratory Diseases\n•Anticipated supply of maternal RSV vaccine and nirsevimab\n•Updates on post -introduction nirsevimab and maternal RSV vaccine safety \nand effectiveness monitoring\n•Revaccination of pregnant people during subsequent pregnanciesOutline\n•For maternal RSV vaccine, no anticipated supply/demand mismatch \n•For nirsevimab, limited availability beginning early September, ramping up \nduring September, broadly available by October 1\n•Original ACIP recommendations (as published in MMWR ) apply for 2024 -\n25 RSV season\n•All infants are recommended to be protected by either maternal RSV \nvaccination or nirsevimab for the 2024 -25 RSV seasonAnticipated supply of maternal RSV vaccine and \nnirsevimab for 2024 –2025 RSV season\nUpdates on post -introduction nirsevimab and \nmaternal RSV vaccine safety and effectiveness \nmonitoring\n•Among reports received in VAERS after maternal Pfizer RSV vaccine, the \nmost frequent adverse events reported were local and systemic symptoms \n(e.g., headache) and pregnancy specific conditions (e.g., preterm delivery)\n-Expected for a vaccine recommended for pregnant persons at 32 -36 weeks’ \ngestation\n-No verified reports of Guillain Barré syndrome\n•Preliminary findings in the Vaccine Safety Datalink (VSD) suggest that the \nincidence of preterm births is 4.1% among pregnant persons who received \nPfizer RSV vaccine during the 2023 -2024 respiratory season \n-Within VSD’s expected historical range of the incidence of preterm births at 32 -36 \nweeks’ gestation (3.1–6.1%) before introduction of this vaccine \n-Matched analysis for preterm birth and other safety outcomes is in progressMaternal RSV vaccine safety\nThe Vaccine Adverse Event Reporting System (VAERS)\nVaccine Safety Datalink (VSD) | CDC\n•Suspected adverse reactions after nirsevimab administration are \nrecommended to be reported to MedWatch\n-These reports are entered into the FDA Adverse Event Reporting System (FAERS) \ndatabase\n•If administered on the same day as a vaccine, suspected adverse reactions \nafter nirsevimab are reported to VAERS\n-FDA/CDER reviewers review these VAERS reports\n•Similar to VAERS, an incidence of an adverse event cannot be determined \nfrom voluntary reportingNirsevimab adverse event reporting \nFDA Adverse Event Reporting System (FAERS) Public Dashboard | FDA\n•The most frequently reported adverse events involved patients who \nreportedly developed breakthrough RSV infections despite receiving \nnirsevimab, and included signs, symptoms, or complications of these \ninfections (e.g., bronchiolitis)\n•Cases of serious hypersensitivity reactions with nirsevimab were identified \nin the post -marketing setting and the product labeling was updated in \nFebruary 2024\n-Serious hypersensitivity reactions have been reported following BEYFORTUS \nadministration. These reactions included urticaria, dyspnea, cyanosis, and/or \nhypotonia. \n•No additional safety signals have been identified at this timeSummary of nirsevimab post -marketing adverse \nevents reported to FAERS and VAERS\nFDA Adverse Event Reporting System (FAERS) Public Dashboard | FDA\n•Safety data on nirsevimab  and maternal RSV vaccine are reassuring, but \npopulation -based studies with comparison groups are needed and pending\n•Because of U.S. recommendation that Pfizer maternal RSV vaccine be given \nat 32 –36 weeks gestation, unlikely to accumulate U.S. data on safety of \nvaccine given at 24 –31 weeks gestation\n•Hypersensitivity reactions in young infants are rare and can be difficult to \ndiscern from startle reactions or vasovagal reactions1WG considerations on safety\n1Agrabenhenrich  et al. 2016 J Allergy Clin Immunol\n•Effectiveness against RSV -associated hospitalization was 91% in NVSN and \n98% in VISION\n•Effectiveness against any medically attended RSV -associated ARI episode \nin NVSN was 89%, and effectiveness against RSV -associated ED visits was \n77% in VISION\n•CDC platform estimates are consistent with studies in Europe,1 \n•Longer follow up time needed to determine duration of protection\n•Limited impact on RSV hospitalization burden, likely because of late \nadministration\n-Substantial decreases in RSV -associated hospitalizations in young infants reported \nin Spain, Luxembourg, and Italy with early implementation and high coverage2Nirsevimab effectiveness\n1 Consolati  Vaccine 2024 ; Ezpeleta  Vaccine 2024 ; Lopez -Lacort  Eurosurveillance 2024 ; Ares -Gomez Lancet Inf Dis 2024;  Coma SSRN preprint 2024 ;\n2Ernst Eurosurveillance 2024 ; Consolati  Vaccine 2024 ; Mazagatos  Influenza Other Respir Viruses 2024  \n•Unable to estimate maternal RSV vaccine effectiveness during the 2023 -24 \nseason due to\n-Limited uptake of maternal RSV vaccine  \n-Early onset of the 2023 -2024 RSV season\n-Timing of vaccine rollout\n•CDC will continue to monitor maternal RSV vaccine effectiveness in future \nseasonsMaternal RSV vaccine effectiveness\n•Evidence shows nirsevimab to be highly effective\n•Duration of protection from nirsevimab and maternal vaccination remains \nunknown\n•Important studies are needed for 2024 -25 season and future RSV seasons\n-Maternal vaccine effectiveness\n-Nirsevimab effectiveness with longer follow up time, which should be available \nwith earlier widespread availability\n-Nirsevimab effectiveness among children aged 8 –19 months with increased risk \nfor severe disease during their second RSV season\n-Impact on RSV burden when nirsevimab and maternal vaccine are given with \nearlier administration and potentially increased uptakeWG considerations on effectiveness\nRevaccination of pregnant people during \nsubsequent pregnancies\n•ACIP recommendations for Pfizer RSV maternal vaccine state that \n-Currently, no data are available on either the efficacy of the first lifetime dose to \nprotect infants born after subsequent pregnancies or the safety of additional \ndoses given during subsequent pregnancies. Additional data are needed to \ndetermine whether additional seasonal doses during subsequent pregnancies are \nindicated, and ACIP might update recommendations in the future, as data become \navailable.\n•Still no data on additional RSV vaccine doses in subsequent pregnancies\n•There are potentially people who received an RSV vaccine during \npregnancy for the 2023 -24 RSV season who could have a subsequent \npregnancy during the 2024 -2025 RSV seasonAdditional RSV vaccine doses in subsequent \npregnancies\nPfizer ABRSYSVO vaccine efficacy against primary clinical trial \noutcomes over time among adults aged ≥60 years\nVaccine Primary outcomeEfficacy (95% CI), \nmonths 0 –12aEfficacy (95% CI),\nmonths 13 –24a\nPfizer ABRYSVORSV LRTI with ≥2 lower \nrespiratory sx62%  (41, 76)\nMedian 12 months follow -up per \nparticipant55%  (26, 73)\nMedian 6 months follow -up per \nparticipant\nRSV LRTI with ≥3 lower \nrespiratory sx86%  (63, 96)\nMedian 12 months follow -up per \nparticipant74%  (27, 92)\nMedian 6 months follow -up per \nparticipant\nAbbreviations: CI: confidence interval, LRTI: lower respiratory tract illness, sx: signs or symptoms, LRTD: lower respiratory tract disease\na.Nominal 12 -month efficacy. Not all trial participants contributing to each estimate had 12 months’ follow up time. Median per -\nparticipant follow -up time is reported below each estimate.\n•Antibody titer lower following 2nd dose at 12 months than initial response\n•Antibody titer prior to 2nd dose above baselinePfizer RSV vaccine Phase 1/2 immunogenicity results in \nnonpregnant adults\nJ Infect Dis , jiae185, https://doi.org/10.1093/infdis/jiae185\n•ACIP Tdap recommendations state that \"When ACIP considered \nrecommending Tdap vaccination during each pregnancy, the safety \ninformation concerning booster doses of Tdap in pregnant women \npreviously vaccinated with Tdap was not available\"\n•\"ACIP recognized the need for safety studies of severe adverse events \nwhen Tdap is administered during subsequent pregnancies but concluded \nthat the potential benefit of preventing pertussis morbidity and mortality \nin infants too young to be fully vaccinated outweighs the theoretical \nconcern of possible localized severe adverse events in pregnant women \nreceiving Tdap. ACIP also concluded that experience with tetanus toxoid –\ncontaining vaccines suggests no excess risk for severe adverse events \namong women receiving Tdap with each pregnancy.\"Tdap recommended during each pregnancy\nPrevention of Pertussis, Tetanus, and Diphtheria with Vaccines in the United States: Recommendations of the Advisory Committe e on Immunization Practices \n(ACIP) | MMWR (cdc.gov)\nUpdated Recommendations for Use of Tetanus Toxoid, Reduced Diphtheria Toxoid, and Acellular Pertussis Vaccine (Tdap) in Pregn ant Women — Advisory \nCommittee on Immunization Practices (ACIP), 2012 (cdc.gov)\n•Concerning that data in older adults suggest revaccination does not \nrestore antibody levels to those after first dose\n-Antibody levels are particularly important for maternal vaccination since infants \nare protected through transplacental transfer of antibodies \n•RSV vaccine differs from Tdap vaccine\n-Maternal RSV vaccine has a potential safety concern for preterm birth and \nhypertensive disorders of pregnancy\n-Alternative product, nirsevimab, exists that can protect infants from severe RSV \nfor subsequent pregnanciesWG consideration on additional RSV vaccine doses in \nsubsequent pregnancies\nhttps://www.cdc.gov/mmwr/volumes/72/wr/mm7241e1.htm  \n•Additional data are needed prior to recommending RSV vaccine during \neach pregnancy (i.e., during subsequent pregnancies)\n-Antibody data in pregnant people and infants with vaccination during subsequent \npregnancies\n-Safety data (e.g., reactogenicity) with vaccination during subsequent pregnancies\n-Safety data of RSV vaccine during the first pregnancy it is administered, \nparticularly regarding outcomes of preterm birth and hypertensive disorders of \npregnancyWG considerations for needed data to make RSV vaccine \nrecommendations during subsequent pregnancies\n•People who received a maternal RSV vaccine during a previous pregnancy \nare not recommended to receive additional doses during future \npregnancies\n•Infants born to people who were vaccinated only during a prior pregnancy \nshould receive nirsevimab\n•Recommendations can be updated in the future if additional data are \navailableRecommendations for additional RSV vaccine doses in \nsubsequent pregnancies\nhttps://www.cdc.gov/mmwr/volumes/72/wr/mm7241e1.htm  \nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position \nof the Centers for Disease Control and Prevention.", "summary": "Maternal/Pediatric RSV Work Group Considerations CDR Jefferson Jones, MD MPH FAAP, USPHS Co-lead, Respiratory Syncytial Virus Vaccines – Maternal/Pediatric  Work Group Coronavirus and Other Respiratory Viruses Division ACIP General Meeting June 28, 2024National Center for Immunization and Respiratory Diseases •Anticipated supply of maternal RSV vaccine and nirsevimab •Updates on post -introduction nirsevimab and maternal RSV vaccine safety  and effectiveness monitoring •Revaccination of…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/05-RSV-Mat-Peds-Jones-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 20}
{"title": "01 HPV brooks 508", "content": "Introduction to the HPV Vaccines Work Group\nOliver Brooks, MD\nChair, HPV Vaccine Work Group\nAdvisory Committee on Immunization Practices\nJune 28, 2024\nNational Center for Immunization & Respiratory Diseases\n2006      2011      2016    2019  Recommendation  for Females\nRoutine : 11 or 12 years , \ncan be started at age 9 \nCatch -up: through  26 years \n3-dose  scheduleEvolution  of HPV  vaccination  recommendations  – \nUnited  States\n2Recommendation  for Males \nRoutine : 11 or 12 years , \ncan be started at age 9\nCatch -up: through  21 years \n3-dose  schedule2-dose  schedule \nif first dose  \nage <15 yearsCatch -up: through  26 \nShared  clinical  decision - \nmaking : some  adults\n27 through  45 years\n2006      2011      2016    2019  Recommendation  for Females\nRoutine : 11 or 12 years , \ncan be started at age 9 \nCatch -up: through  26 years \n3-dose  scheduleEvolution  of HPV  vaccination  recommendations  – \nUnited  States\n3Recommendation  for Males \nRoutine : 11 or 12 years , \ncan be started at age 9\nCatch -up: through  21 years \n3-dose  schedule2-dose  schedule \nif first dose  \nage <15 yearsCatch -up: through  26 \nShared  clinical  decision - \nmaking : some  adults\n27 through  45 years\nQuadrivalent Vaccine\nBivalent VaccineVaccines \navailable \n9-valent Vaccine\n•Routine vaccination\n-Age 11 or 12 years \n-Can be started at age 9 years \n•Catch -up vaccination \n-Through age 26 years\n•Shared clinical decision -making \n-Age 27–45 yearsCurrent HPV vaccination recommendations, \nUnited States\nRecommendations of the Centers for Disease Control and Prevention and the Advisory Committee on Immunization Practices \nhttps://www.cdc.gov/vaccines/hcp/acip -recs/vacc -specific/hpv.html  Number of doses\n2 doses  (0, 6 -12 months) \nif starting series before 15th birthday\n3 doses  (0,1-2, 6 months) \nif starting series on or after 15th birthday or if \nimmunocompromising condition\n4\n•Number of doses in the recommended HPV vaccination series\n•Wording of the age for routine vaccination\n•Guidance regarding persons in the “shared clinical decision -making” age \nrange (27 –45 years)Topics to be considered by HPV Vaccines Work Group\n5\n•Number of doses in the recommended HPV vaccination series\n-Accumulating evidence on efficacy of HPV vaccination with fewer doses\n-In 2022, the World Health Organization recommended a two -dose schedule for \npersons aged 9 years or older and, a s an off -label option, a single -dose schedule \ncan be used for those aged 9 –20 yearsTopics to be considered by HPV Vaccines Work Group\n6\n•Wording of the age for routine HPV vaccination\n-Some stakeholders interested in starting vaccination at age 9 years\n-Current ACIP recommendations are consistent with vaccination at age 9 years\n-Modification of wording could allow more flexibility Topics to be considered by HPV Vaccines Work Group\n7\n•Guidance regarding persons in the “shared clinical decision -making” age \nrange (27 –45 years)\n-Shared clinical decision -making recommendation made in 2019\n-Interest in providing more guidance for subgroups in this age rangeTopics to be considered by HPV Vaccines Work Group\n8\n•July 2024 – first meeting of Work Group\n•October 2024 – presentation of general issues to full ACIP\n-Number of doses in the HPV vaccination schedule\n-Routine age recommendation wordingACIP HPV Vaccines Work Group initial timeline\n9\nACIP HPV Vaccines Work Group\nChair\n•Oliver Brooks\nCDC Co -Leads\n•Lauri Markowitz\n•Carla DeSistoWork Group Members\n•Pending \n10", "summary": "Introduction to the HPV Vaccines Work Group Oliver Brooks, MD Chair, HPV Vaccine Work Group Advisory Committee on Immunization Practices June 28, 2024 National Center for Immunization & Respiratory Diseases 2006      2011      2016    2019  Recommendation  for Females Routine : 11 or 12 years ,  can be started at age 9  Catch -up: through  26 years  3-dose  scheduleEvolution  of HPV  vaccination  recommendations  –  United  States 2Recommendation  for Males  Routine : 11 or 12 years ,  can be…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/01-HPV-brooks-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 10}
{"title": "01 COVID Daley 508", "content": "Centers for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nACIP COVID- 19 Vaccines Work Group\nDr. Matthew F. Daley, Work Group Chair\nFebruary 28, 2024\nACIP met September 12, 2023 to review the available evidence for updated (2023- 2024 Formula) COVID-\n19 vaccines.\nACIP recommended updated COVID- 19 vaccines as authorized under EUA or approved by BLA in persons \naged ≥6 months.\n–Moderna COVID -19 vaccine in persons ≥6 months \n–Pfizer -BioNTech COVID- 19 vaccine in persons ≥6 months \n–Novavax COVID -19 vaccine in persons ≥ 12 years*\nEveryone aged 5 years and older should get 1 dose of an updated COVID- 19 vaccine to protect against \nserious illness from COVID -19.\nChildren aged 6 months –4 years need multiple doses of COVID -19 vaccines to be up to date, including at \nleast 1 dose of updated COVID- 19 vaccine.\nPeople who are moderately or severely immunocompromised may get additional doses of updated \nCOVID -19 vaccine.COVID- 19 vaccine policy\nNote: Updated (2023 – 2024 Formula) COVID -19 vaccines are monovalent vaccines containing an XBB.1.5 component\nAbbreviations – EUA: Emergency Use Authorization, BLA: Biologics License Application\n*People aged 12 years and older who have not previously gotten any COVID -19 vaccine doses and choose to get Novavax should get 2  doses of updated Novavax vaccine to be \nup to date.\nReviewed and discussed:\nCOVID -19 vaccine implementation    \nCOVID -19 policy updatesACIP COVID- 19 Meeting Review: October 2023\nCOVID -19 hospitalizations – COVID -NET   Dr. Christopher Taylor \nCOVID -19 vaccine coverage    Dr. Kevin Chatham -Stephens\nCOVID -19 vaccine effectiveness     Dr. Ruth Link -Gelles\nEconomic analysis of additional dose    Dr. Lisa Prosser\nEvidence to Recommendations     Dr. Megan Wallace\nNext steps for COVID -19 vaccine program    Dr. Lakshmi Panagiotakopoulos\nVote: Additional Dose of COVID -19 Vaccine   Dr. Megan WallaceAgenda\nFebruary 28, 2024\nWork Group members\nACIP members\nMatthew Daley (chair)\nOliver Brooks\nEx-officio/government members\nFDA: Rachel Zhang, Lucia Lee, Anuja Rastogi,\n      Adam Spanier\nNIH: Chris Roberts, Michael Ison\nIHS: Uzo Chukwuma\nCMS: Jeff Kelman\nBARDA: Christine Oshansky\nHHS: Valerie Marshall\nCDC: Alan Lam\nCDC co- Leads\nMegan Wallace\nLakshmi Panagiotakopoulos\n5Liaisons\nAAFP: Jonathan Temte\nAAP: Sean O’Leary\nACOG: Denise Jamieson (primary), \nLaura Riley (alternate)\nACP: Jason Goldman\nAGS: Ken Schmader\nAMA: Sandra Fryhofer\nANA: Ruth Francis \nAPhA : Richard Dang\nASTHO: Marcus Plescia\nCSTE: Paul Cieslak, Christine Hahn\nIDSA: Jeff Duchin (primary)Liaisons, cont’d\nNACCHO: Matt Zahn (primary), Jeff Duchin (alternate)\nNACI: Matthew Tunis (primary),    Eva Wong (alternate)  \nNFID: Rob Schechter  (primary),        \nBill Schaffner  (alternate)\nNMA: Patricia Whitley -Williams\nSHEA:  Preeti Mehrotra,                \nMarci Drees (alternate)\n   \nConsultants\nBeth Bell\nEd Belongia  \nHank Bernstein \nKathy Edwards  \nRobert Hopkins\nLisa Jackson\nKathy KinlawGrace Lee\nDayna Matthew\nJennifer Nelson\nKathleen Neuzil\nStanley Perlman\nPeter Szilagyi\nKeipp Talbot\nSarah Meyer\nElisha Hall\nDanielle Moulia\nMonica Godfrey\nHannah Rosenblum\nKatherine Fleming -Dutra\nRuth Link -Gelles\nLauren Roper \nMary Chamberland\nSusan Goldstein\nStephen Hadler\nJoEllen Wolicki\nMelinda Wharton\nJessica MacNeil\nAmanda Cohn\nLatifa Boyce \nAmadea BrittonCDC participants\n6Karen Broder \nCarolyn Bridges\nAllison Ciesla \nNicole Dowling\nDaniel Drapeau\nTarayn Fairlie\nKristen Folsom\nAshley Fowlkes\nJarrett Gartin\nJulianne Gee\nSamuel Graitcer\nElizabeth Greene\nLisa Grohskopf\nAron Hall \nDemorah Hayes\nRita Helfand\nTerri Hyde \n Melisa Shah\nTom Shimabukuro\nJordan Singleton\nLaura Steinhardt\nJohn Su\nNatalie Thornburg\nEvelyn Twentyman \nDennis Wang\nRaigan Wheeler\nRyan Wiegand\nTrang Wisard\nPatricia Yu\nYon YuJefferson Jones \nAndrew Kroger\nJosephine Mak\nLauri Markowitz\nMichael McNeil\nMichael Melgar\nNoelle -Angelique Molinari\nMorgan Najdowski\nKristen Nordlund\nIsmael Ortega -Sanchez\nManisha Patel\nPragna Patel\nAmanda Payne\nGeorgina Peacock\nJamison Pike\nDerrell Powers  \nSierra Scarbrough \nFor more information, contact CDC\n1-800- CDC- INFO (232 -4636)\nTTY:  1 -888 -232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention.\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nThank you", "summary": "Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. ACIP COVID- 19 Vaccines Work Group Dr. Matthew F. Daley, Work Group Chair February 28, 2024 ACIP met September 12, 2023 to review the available evidence for updated…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-28-29-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-02-28-29/01-COVID-Daley-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 7}
{"title": "02 COVID Taylor 508", "content": "Centers for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nCOVID- 19–Associated Hospitalizations among\nAdults — COVID- NET, 2023 –2024\nAdvisory Committee on Immunization Practices (ACIP)\nFebruary 28, 2024\nChristopher A. Taylor, PhD\nRESP- NET Hospitalization Surveillance Team\nSurveillance and Prevention Branch\nCoronavirus and Other Respiratory Viruses Division\nRESP -NET: COVID -NET, RSV -NET, FluSurv -NET\n>300 acute -care hospitals\n98 counties in 13 states\nIn 9 of 10 HHS regions\n~10% of U.S. population\nPositive SARS-CoV -2 within 14 days of or \nduring hospitalization\nScreening or clinician-driven testing\nClinical data: representative sample of \nCOVID -NET patientsCOVID -NET: A RESP -NET population -based hospitalization \nsurveillance platform\n\nEpidemiology of COVID -19–associated \nhospitalizations among adults\nWeekly Population -Based Rates of COVID -19-Associated \nHospitalizations — COVID -NET, March 2020– January 2024\n020406080100120140\n3/7/2020\n5/7/2020\n7/7/2020\n9/7/2020\n11/7/2020\n1/7/2021\n3/7/2021\n5/7/2021\n7/7/2021\n9/7/2021\n11/7/2021\n1/7/2022\n3/7/2022\n5/7/2022\n7/7/2022\n9/7/2022\n11/7/2022\n1/7/2023\n3/7/2023\n5/7/2023\n7/7/2023\n9/7/2023\n11/7/2023\n1/7/2024Rate per 100,000 population\nWeek Ending DateMarch 1, 2020 –January 27, 2024\n18–49 years 50–64 years 65–74 years ≥75 years020406080100120140\n10/7/2023 11/7/2023 12/7/2023 1/7/2024Rate per 100,000 population\nWeek Ending DateOctober 2023 –January 2024\nGray boxes indicate potential reporting delays. Interpretation of trends should be excluded from these weeks. Rates highest in adults ages ≥75 years.\nPercent of Weekly Hospitalizations by Age Group —\nCOVID -NET, March 2020– January 2024\n0%10%20%30%40%50%60%70%80%90%100%\n3/7/2020\n4/11/2020\n5/16/2020\n6/20/2020\n7/25/2020\n8/29/2020\n10/3/2020\n11/7/2020\n12/12/2020\n1/16/2021\n2/20/2021\n3/27/2021\n5/1/2021\n6/5/2021\n7/10/2021\n8/14/2021\n9/18/2021\n10/23/2021\n11/27/2021\n1/1/20222/5/2022\n3/12/20224/16/20225/21/20226/25/2022\n7/30/2022\n9/3/2022\n10/8/2022\n11/12/202212/17/2022\n1/21/20232/25/2023\n4/1/2023\n5/6/2023\n6/10/2023\n7/15/2023\n8/19/2023\n9/23/2023\n10/28/2023\n12/2/2023\n1/6/2024Percent of COVID -19-associated hospitalizations\nWeek ending date\n≤17 years 18–49 years 50–64 years 65–74 years 75–84 years ≥85 years≥65: 67%  of COVID -19 \nhospitalizations October \n2023– January 2024\n<65: 33%  of COVID -19 \nhospitalizations October 2023– January 2024≥75: 46%  of COVID -19 \nhospitalizations October 2023–January 2024\n05101520253035\nOctober\n2022November\n2022December\n2022January\n2023February\n2023March 2023 April 2023 May 2023 June 2023 July 2023 August 2023 September\n2023October\n2023November\n2023Weighted % of COVID -19-Associated HospitalizationsAmong adults ages ≥75 years during October 2022–November 2023, 25% of \nCOVID -19-associated hospitalizations were residents of a long -term care \nfacility.\n01234567\n18–49 years 50–64 years 65–74 years ≥75 years All AdultsWeighted % of Hospitalizations1.4%, \nN=383.3%, \nN=555.5%, \nN=70\n4.0%, \nN=853.8%, \nN=238Percent of COVID -19-Associated Hospitalizations Resulting in In -Hospital \nDeath, by Age Group — COVID -NET, October 2022 –November 2023\nAn examination of death certificate data from March 2020 –April 2022 found that among all deaths in adults with COVID -19-associat ed hospitalization, \n67% occurred in -hospital and 33% occurred ≤30 days post -discharge. Among adults ages ≥65 \nyears who died in -hospital, \n28%  were residents of \nlong -term care facilities.\nPercent of COVID-19 -Associated Hospitalizations with \nImmunocompromising Conditions*, by Age Group —\nCOVID -NET, October 2022 –November 2023\n121921\n1316\n051015202530\n18–49 years 50–64 years 65–74 years ≥75 years All AdultsWeighted % of hospitalizations\n* Immunocompromising conditions include AIDS or CD4 count<200, complement deficiency, graft vs host disease, HIV, immunoglobu lin deficiency, receipt of immunosuppressive therapy, \nleukemia, lymphoma, solid organ malignancy, bone marrow transplant, metastatic cancer, multiple myeloma, steroid therapy, solid organ transplant, and other conditions adjudicated by \nRESP -NET physicians to be immunocompromising in nature.\nPercent of COVID -19-Associated Hospitalizations with Immunocompromising \nConditions among All Adults Ages ≥18 Years, Overall and by Outcome — COVID -NET, \nOctober 2022– November 2023\n16% 17%28%\n0%10%20%30%40%50%60%70%80%90%100%\nAll Hospitalizations ICU Admissions In-Hospital DeathsWeighted % of Hospitalizations\nImmunocompromised Not Immunocompromised\n* Immunocompromising conditions include AIDS or CD4 count<200, complement deficiency, graft vs host disease, HIV, immunoglobu lin deficiency, receipt of immunosuppressive therapy, \nleukemia, lymphoma, solid organ malignancy, bone marrow transplant, metastatic cancer, multiple myeloma, steroid therapy, solid organ transplant, and other conditions adjudicated by \nRESP -NET physicians to be immunocompromising in nature.N=75\n(of 251\ndeaths)N=206\n(of 1,035 ICU \nadmissions)\nPercent of Hospitalizations among Adults Ages ≥18 Years with Underlying Medical Conditions \nby Age Group, with Top 4 Conditions Highlighted — COVID -NET, October 2022 –November 2023\nCondition 18–49 yrs 50–64 yrs 65–74 yrs ≥75 yrs\nChronic lung disease 23 36 45 34\nAsthma 19 17 14 9\nCOPD/Bronchitis 3 16 24 16\nCardiovascular disease 20 47 61 67\nCAD/CABG/MI 5 17 27 27\nCHF/Cardiomyopathy 6 18 25 25\nStroke/TIA 3 13 15 20\nDiabetes 21 40 44 37\nImmunocompromising condition 12 19 21 13\nNeurologic condition 18 26 30 42\nDementia 0 1 6 29\nRenal Disease 8 21 24 31\nObesity 42 43 39 23\nCOVID -19 Vaccination Status by Age Group among Adults Ages ≥18 Years \nHospitalized with COVID -19 — COVID -NET, October –November 2023 (Preliminary)\nNo record of bivalent or updated monovalent dose : No recorded doses of COVID -19 bivalent or updated 2023 -2024monovalent dose. Bivalent booster, but no updated monovalent doses : \nReceived COVID -19 bivalent booster vaccination but no record of receiving updated 2023 -2024 monovalent booster dose. Updated monovalent dose: Received updated 2023- 2024 monovalent \ndose  Persons with unknown vaccination status are excluded  87\n73677012\n2528252 2 5 4\n0%10%20%30%40%50%60%70%80%90%100%\n18–49 years 50–64 years ≥65 years All Adults, ≥18 yearsWeighted percent of hospitalizations\nNo record of  bivalent or updated monovalent dose Bivalent booster, but no updated monovalent dose Updated monovalent dose\nCoronavirus and Other Respiratory \nViruses Division\nFiona Havers\nHuong Pham\nKadam Patel\nMichael Whitaker\nRESP -NET Site investigators and staffAcknowledgements\nFor more information, contact CDC\n1-800- CDC- INFO (232 -4636)\nTTY:  1 -888 -232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention.\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.", "summary": "Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. COVID- 19–Associated Hospitalizations among Adults — COVID- NET, 2023 –2024 Advisory Committee on Immunization Practices (ACIP) February 28, 2024 Christopher A. Taylor,…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-28-29-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-02-28-29/02-COVID-Taylor-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 13}
{"title": "03 COVID Chatham Stevens 508", "content": "National Center for Immunization & Respiratory Diseases\nAn update on COVID- 19 vaccination coverage \nCDR Kevin Chatham -Stephens, MD, MPH, FAAP\nReadiness and Response Lead\nImmunization Services DivisionNational Center for Immunizations and Respiratory Diseases (NCIRD)\nCOVID -19 vaccination coverage\nPercent of adults and children up- to-date with 2023– 24 \nCOVID -19 Vaccine\nNational Immunization Survey -Adult COVID Module (NIS -ACM) and - Child COVID Module (NIS -CCM)\n0.010.020.030.040.050.0\n9/30/23\n10/7/23\n10/14/23\n10/21/23\n10/28/23\n11/4/23\n11/11/23\n11/18/23\n11/25/23\n12/2/23\n12/9/23\n12/16/23\n12/23/2312/30/23\n1/6/24\n1/13/241/20/24\n1/27/24\n2/3/24Vaccinated with 2023 -24 COVID -19 vaccine (%)\nWeek end dateAll children 6m-17y\n12-17y\n5-11y\n6m-4y\n0.010.020.030.040.050.0\n9/30/23\n10/7/23\n10/14/23\n10/21/2310/28/23\n11/4/23\n11/11/23\n11/18/23\n11/25/23\n12/2/2312/9/23\n12/16/2312/23/2312/30/23\n1/6/24\n1/13/241/20/24\n1/27/24\n2/3/24Vaccinated with 2023 -24 COVID- 19 vaccine (%)\nWeek end dateAll adults 18+\n75+\n65-74\n50-64\n40-49\n30-39\n18-29COVID -19 Vaccination Coverage with 2023- 24 Vaccine \nAmong Adults ≥18 Years, NIS -ACMCOVID -19 Vaccination Coverage with 2023- 24 Vaccine \nAmong Children 6 Months -17 Years, NIS -CCM\nCOVID -19 vaccination status among adults ≥18 years by jurisdiction* \nNational Immunization Survey-Adult COVID Module (NIS -ACM)\nAcross jurisdictions, range of \nvaccination coverage among adults 18 and older:\n•Lowest jurisdiction: Puerto Rico \n9.5% (95% CI: 8.0- 11.0)\n•Lowest state: Mississippi 10.5% \n(95% CI: 8.4- 12.5)\n•Highest jurisdiction: District of \nColumbia 41.9% (95% CI: 37.0-46.8)\n*As of week ending 2/3/24\nCOVID -19 vaccination status and intent among adults ≥18 years\nNational Immunization Survey -Adult COVID Module (NIS -ACM)*\nProbably or definitely will not get vaccinated\nProbably will get vaccinated or unsureDefinitely will get vaccinatedVaccinated with 2023 -24 COVID -19 vaccine\n3.0 4.0 6.1 8.2 9.5 11.9 13.2 14.5 14.8 17.1 17.9 18.2 18.6 18.9 20.6 21.0 21.4 21.7 21.928.2 27.2 24.924.2 19.718.6 18.1 15.1 14.714.6 14.2 12.0 13.1 13.314.3 12.7 11.7 11.4 11.331.7 31.9 31.0 29.329.230.1 28.8 30.1 31.230.3 27.2 29.4 28.9 28.227.6 28.2 28.2 28.1 28.537.1 36.8 38.0 38.241.6 39.4 39.9 40.3 39.3 38.0 40.7 40.4 39.5 39.6 37.5 38.1 38.7 38.8 38.3\n0255075100Weighted %\n*Sample size = 257,352\n\nCOVID -19 vaccination status and intent among adults ≥18 years\nNational Immunization Survey -Adult COVID Module (NIS -ACM)*\nProbably or definitely will not get vaccinated\nProbably will get vaccinated or unsureDefinitely will get vaccinatedVaccinated with 2023 -24 COVID -19 vaccine\n3.0 4.0 6.1 8.2 9.5 11.9 13.2 14.5 14.8 17.1 17.9 18.2 18.6 18.9 20.6 21.0 21.4 21.7 21.928.2 27.2 24.924.2 19.718.6 18.1 15.1 14.714.6 14.2 12.0 13.1 13.314.3 12.7 11.7 11.4 11.331.7 31.9 31.0 29.329.230.1 28.8 30.1 31.230.3 27.2 29.4 28.9 28.227.6 28.2 28.2 28.1 28.537.1 36.8 38.0 38.241.6 39.4 39.9 40.3 39.3 38.0 40.7 40.4 39.5 39.6 37.5 38.1 38.7 38.8 38.3\n0255075100Weighted %\n*Sample size = 257,352Note: The analysis of coverage \nby demographics on the \nfollowing slides is based on \nsurvey responses from the time \nperiod December 31, 2023-\nJanuary 27, 2024\n\nCOVID -19 vaccination status among adults ≥18 years, January 2024\nNational Immunization Survey -Adult COVID Module (NIS -ACM)*\n24.419.216.419.413.314.111.423.218.620.9\n0.0 20.0 40.0 60.0 80.0 100.0WhiteAsianBlackMulti/OtherHispanicNH/OPIAI/ANFemaleMaleOverall 18+\nWeighted % (95% CI)•Among adults ≥18 years responding to the \nNIS-ACM during 12/31/23 –1/27/24:\n•20.9% (95% CI: 20.3- 21.6) reported that they \nhave received an updated 2023 -24 COVID -19 \nvaccine.\n•By demographics:\n•Vaccination coverage was significantly higher \namong females (23%).\n•Vaccination coverage was highest among White non-Hispanic adults (24%) and lowest among \nAI/AN (11%), NH/OPI (14%), and Hispanic (13%) adults.\n*Sample size = 60,840\nCOVID -19 vaccination status among adults ≥18 years, January 2024\nNational Immunization Survey -Adult COVID Module (NIS -ACM)*\n21.020.618.726.119.412.76.922.716.821.321.9\n0.0 20.0 40.0 60.0 80.0 100.0Disability: noneDisability: anyIncome unknownAbove poverty, >=$75KAbove poverty, <$75KBelow povertyUninsuredInsuredRuralSuburbanUrban\nWeighted % (95% CI)•By urbanicity: \n•COVID -19 vaccination coverage was lowest in \nrural areas (17%).\n•By health insurance status: \n•Adults with health insurance had significantly \nhigher vaccination coverage (23%) than adults without insurance (7%).\n•By household income:\n•Vaccination coverage increased with increasing household income; highest among those with \nincome ≥$75k (26%).\n*Sample size = 60,840\nPercent of pregnant persons 18 –49 years vaccinated with 2023–24 \nCOVID -19 Vaccine (Vaccine Safety Datalink) \n•Among pregnant \npersons ages 18 –49 \nyears, 12.5% have received an \nupdated 2023- 24 \nCOVID -19 vaccine \nas of 1/27/24.\n•Coverage varies by \nrace/ethnicity; ranges from 4.8% \n(Black non-\nHispanic) to 21.3% \n(Asian).\n\nAttitudes and experiences regarding COVID -\n19 vaccination\nMost frequent COVID-19 vaccination concerns among adults ≥18 \nyears by vaccination status/intent (Omnibus Surveys January 5 –29, 2024*)\n10.1%\n6.4%\n6.3%\n5.9%\n74.1%\n0 25 50 75 100Mild side\neffects\nImpact of side effects\non work/school\nUnknown serious\nside effects\nEffectiveness\nNo concerns\nWeighted % (95% confidence interval)Received/definitely will get\n(N=1,296)\n15.5%\n12.7%\n12.3%\n11.8%\n40.7%\n0 25 50 75 100Unknown serious\nside effects\nToo busy or\nkept forgetting\nEffectiveness\nMild side\neffects\nNo concerns\nWeighted % (95% confidence interval)Probably will get/unsure\n(N=1,003)\n47.0%\n39.0%\n37.2%\n33.2%\n32.9%\n0 25 50 75 100Unknown serious\nside effects\nNot enough studies\n(human trials)\nDo not trust\ngov. or pharma\nHeart- related\nissues\nEffectiveness\nWeighted % (95% confidence interval)Probably/definitely will NOT get\n(N=1,861)\n*Sample size = 4,160\nMost frequent COVID-19 vaccination concerns among adults ≥18 \nyears by vaccination status/intent (Omnibus Surveys January 5 –29, 2024*)\n10.1%\n6.4%\n6.3%\n5.9%\n74.1%\n0 25 50 75 100Mild side\neffects\nImpact of side effects\non work/school\nUnknown serious\nside effects\nEffectiveness\nNo concerns\nWeighted % (95% confidence interval)Received/definitely will get\n(N=1,296)\n15.5%\n12.7%\n12.3%\n11.8%\n40.7%\n0 25 50 75 100Unknown serious\nside effects\nToo busy or\nkept forgetting\nEffectiveness\nMild side\neffects\nNo concerns\nWeighted % (95% confidence interval)Probably will get/unsure\n(N=1,003)\n47.0%\n39.0%\n37.2%\n33.2%\n32.9%\n0 25 50 75 100Unknown serious\nside effects\nNot enough studies\n(human trials)\nDo not trust\ngov. or pharma\nHeart- related\nissues\nEffectiveness\nWeighted % (95% confidence interval)Probably/definitely will NOT get\n(N=1,861)\n*Sample size = 4,160\nMost frequent COVID-19 vaccination concerns among adults ≥18 \nyears by vaccination status/intent (Omnibus Surveys January 5 –29, 2024*)\n10.1%\n6.4%\n6.3%\n5.9%\n74.1%\n0 25 50 75 100Mild side\neffects\nImpact of side effects\non work/school\nUnknown serious\nside effects\nEffectiveness\nNo concerns\nWeighted % (95% confidence interval)Received/definitely will get\n(N=1,296)\n15.5%\n12.7%\n12.3%\n11.8%\n40.7%\n0 25 50 75 100Unknown serious\nside effects\nToo busy or\nkept forgetting\nEffectiveness\nMild side\neffects\nNo concerns\nWeighted % (95% confidence interval)Probably will get/unsure\n(N=1,003)\n47.0%\n39.0%\n37.2%\n33.2%\n32.9%\n0 25 50 75 100Unknown serious\nside effects\nNot enough studies\n(human trials)\nDo not trust\ngov. or pharma\nHeart- related\nissues\nEffectiveness\nWeighted % (95% confidence interval)Probably/definitely will NOT get\n(N=1,861)\n*Sample size = 4,160\nMost frequent COVID-19 vaccination concerns among adults ≥18 \nyears by vaccination status/intent (Omnibus Surveys January 5 –29, 2024*)\n10.1%\n6.4%\n6.3%\n5.9%\n74.1%\n0 25 50 75 100Mild side\neffects\nImpact of side effects\non work/school\nUnknown serious\nside effects\nEffectiveness\nNo concerns\nWeighted % (95% confidence interval)Received/definitely will get\n(N=1,296)\n15.5%\n12.7%\n12.3%\n11.8%\n40.7%\n0 25 50 75 100Unknown serious\nside effects\nToo busy or\nkept forgetting\nEffectiveness\nMild side\neffects\nNo concerns\nWeighted % (95% confidence interval)Probably will get/unsure\n(N=1,003)\n47.0%\n39.0%\n37.2%\n33.2%\n32.9%\n0 25 50 75 100Unknown serious\nside effects\nNot enough studies\n(human trials)\nDo not trust\ngov. or pharma\nHeart- related\nissues\nEffectiveness\nWeighted % (95% confidence interval)Probably/definitely will NOT get\n(N=1,861)\n*Sample size = 4,160\nMost frequent COVID-19 vaccination concerns among adults ≥18 \nyears by vaccination status/intent (Omnibus Surveys January 5 –29, 2024*)\n10.1%\n6.4%\n6.3%\n5.9%\n74.1%\n0 25 50 75 100Mild side\neffects\nImpact of side effects\non work/school\nUnknown serious\nside effects\nEffectiveness\nNo concerns\nWeighted % (95% confidence interval)Received/definitely will get\n(N=1,296)\n15.5%\n12.7%\n12.3%\n11.8%\n40.7%\n0 25 50 75 100Unknown serious\nside effects\nToo busy or\nkept forgetting\nEffectiveness\nMild side\neffects\nNo concerns\nWeighted % (95% confidence interval)Probably will get/unsure\n(N=1,003)\n47.0%\n39.0%\n37.2%\n33.2%\n32.9%\n0 25 50 75 100Unknown serious\nside effects\nNot enough studies\n(human trials)\nDo not trust\ngov. or pharma\nHeart- related\nissues\nEffectiveness\nWeighted % (95% confidence interval)Probably/definitely will NOT get\n(N=1,861)\n*Sample size = 4,160\nSpecific concerns about effectiveness of updated COVID -19 Vaccines \namong adults ≥18 years who reported effectiveness as a concern\nOmnibus Surveys, January 5 -29, 2024*\n*Sample size = 798\n\nHow people think and feel about COVID -19 vaccines has changed since 2022\nNational Immunization Survey -Adult COVID Module (NIS -ACM)\nDisease risk perception has also changed , \nas reflected in the percentage of Americans \nmoderately/very concerned about getting COVID -19.\nWhile most Americans still consider \nCOVID -19 vaccines to be safe and important, \nvaccine confidence has declined.\nPercent of Adults 18+ years of age that \nthink that a COVID- 19 vaccine  is \nvery/completely safePercent of Adults 18+ years of age that \nthink that a COVID- 19 \nvaccine is somewhat/very importantPercent of Adults 18+ years of age that are \nmoderately/very concerned about getting \nCOVID -19\n55.0%\n32.7%\n2022 January 2024 January83.9%\n69.6%\n2022 January 2024 January67.3%\n55.6%\n2022 January 2024 January\nHow people think and feel about COVID -19 vaccines has changed since 2022\nNational Immunization Survey -Adult COVID Module (NIS -ACM)\nDisease risk perception has also changed , \nas reflected in the percentage of Americans \nmoderately/very concerned about getting COVID -19.\nWhile most Americans still consider \nCOVID -19 vaccines to be safe and important, \nvaccine confidence has declined.\nPercent of Adults 18+ years of age that \nthink that a COVID- 19 vaccine  is \nvery/completely safePercent of Adults 18+ years of age that \nthink that a COVID- 19 \nvaccine is somewhat/very importantPercent of Adults 18+ years of age that are \nmoderately/very concerned about getting \nCOVID -19\n55.0%\n32.7%\n2022 January 2024 January83.9%\n69.6%\n2022 January 2024 January67.3%\n55.6%\n2022 January 2024 January\nHow people think and feel about COVID -19 vaccines has changed since 2022\nNational Immunization Survey -Adult COVID Module (NIS -ACM)\nDisease risk perception has also changed , \nas reflected in the percentage of Americans \nmoderately/very concerned about getting COVID -19.\nWhile most Americans still consider \nCOVID -19 vaccines to be safe and important, \nvaccine confidence has declined.\nPercent of Adults 18+ years of age that \nthink that a COVID- 19 vaccine  is \nvery/completely safePercent of Adults 18+ years of age that \nthink that a COVID- 19 \nvaccine is somewhat/very importantPercent of Adults 18+ years of age that are \nmoderately/very concerned about getting \nCOVID -19\n55.0%\n32.7%\n2022 January 2024 January83.9%\n69.6%\n2022 January 2024 January67.3%\n55.6%\n2022 January 2024 January\nHow people think and feel about COVID -19 vaccines has changed since 2022\nNational Immunization Survey -Adult COVID Module (NIS -ACM)\nDisease risk perception has also changed , \nas reflected in the percentage of Americans \nmoderately/very concerned about getting COVID -19.\nWhile most Americans still consider \nCOVID -19 vaccines to be safe and important, \nvaccine confidence has declined.\nPercent of Adults 18+ years of age that \nthink that a COVID- 19 vaccine  is \nvery/completely safePercent of Adults 18+ years of age that \nthink that a COVID- 19 \nvaccine is somewhat/very importantPercent of Adults 18+ years of age that are \nmoderately/very concerned about getting \nCOVID -19\n55.0%\n32.7%\n2022 January 2024 January83.9%\n69.6%\n2022 January 2024 January67.3%\n55.6%\n2022 January 2024 January\nHealthcare provider COVID -19 vaccine recommendations\nRelative to 2021, adults \nreported fewer providers are \nrecommending COVID -19 \nvaccines\n(National Immunization Survey -Adult \nCOVID Module [NIS -ACM])\nPercent of adults whose healthcare \nprovider recommends COVID -19 vaccine\nMost physicians reported always \nrecommending bivalent boosters\n(CDC/RAND/Univ of Iowa Survey)\n65.4%77.2%80.9%\nPatients 18-49 years Patients 50-64 years Patients aged ≥65 yearsPercent of physicians who reported always recommending on -\nsite bivalent COVID- 19 vaccine to eligible patients — Feb 2023\n36.1%\n20.4%\n2021 May\n(4 mo. after vaccine\navailable)2024 January\n(4 mo. after updated\nvaccine available)\nReasons healthcare providers reported for NOT recommending COVID -19 \nbivalent boosters to eligible adult patients (CDC/RAND/Univ of Iowa Survey — February 2023)\nResponse options receiving <5% for at least one provider group not presented 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%\nMedical reason for not getting vaccinated\nPatient will refuse booster vaccination\nPatients tired of hearing about COVID-19 vaccines\nHigh level of vaccine resistance in community\nOther\nWon't have severe COVID-19 symptoms\nBivalent vaccine doesn't provide enough additional protection\nNot enough time during visit to discuss vaccines\nVaccine unnecessary if they have had COVID-19\nNot enough time during visit to give vaccine\nBivalent vaccine doesn't reduce COVID-19 severity in this age group% of respondents selecting response option (n=744)\nPhysicians\nNurses\nPharmacists\n•Perceived low interest for COVID -19 vaccination in the patient population\n•Cost of the COVID -19 vaccine and other associated vaccination costs\n•Healthcare system decided to not stock the COVID- 19 vaccines\n•Availability of the COVID -19 vaccines elsewhere in the community (e.g., pharmacies)Potential reasons for primary care providers to not stock \nCOVID -19 vaccines\nAccessibility of COVID -19 vaccines\nNational Immunization Survey -Adult COVID Module (NIS -ACM)\nMost Americans reported little to no difficulty in getting a COVID- 19 \nvaccine, across income ranges , in October 2023.\nFewer Americans report \ndifficulty getting COVID -19 \nvaccines in 2024.\n88.9%93.4%92.8% 93.3%94.9%96.1%\n95.3% 95.6%\n6065707580859095100\nLess than\n$5,000$5,001-\n$10,000$10,001-\n$20,000$20,001-\n$40,000$40,001-\n$60,000$60,001-\n$75,000$75,001-\n$150,000$150,001\nor morePercent of adults that reported not at all/a little difficult getting a COVID -19 \nvaccine, by income\n80.5%95.0%\n2021 May 2024 JanuaryPercent of adults that reported not at all/a little \ndifficult getting a COVID -19 vaccine\nAcceptability of getting the Flu, COVID -19, and/or RSV vaccines \nin the same visit among adults ≥18 years\nOmnibus Surveys, November 30 -December 21, 2023*\n*Sample size = 1,951\n\nAcknowledgements\n•Carla Black (CDC)\n•Kayla Calhoun (CDC)\n•Courtney Gidengil (RAND)\n•Elisha Hall (CDC)\n•Jennifer Kriss (CDC)\n•Megan Lindley (CDC)•Sarah Meyer (CDC)\n•Lakshmi Panagiotakopoulos (CDC)\n•Megan Wallace (CDC)\nFor more information, contact CDC\n1-800- CDC- INFO (232- 4636)\nTTY:  1 -888- 232- 6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.", "summary": "National Center for Immunization & Respiratory Diseases An update on COVID- 19 vaccination coverage  CDR Kevin Chatham -Stephens, MD, MPH, FAAP Readiness and Response Lead Immunization Services DivisionNational Center for Immunizations and Respiratory Diseases (NCIRD) COVID -19 vaccination coverage Percent of adults and children up- to-date with 2023– 24  COVID -19 Vaccine National Immunization Survey -Adult COVID Module (NIS -ACM) and - Child COVID Module (NIS -CCM) 0.010.020.030.040.050.0…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-28-29-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-02-28-29/03-COVID-Chatham-Stevens-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 27}
{"title": "04 COVID Link Gelles 508", "content": "1\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nVaccine effectiveness of\nupdated (2023 -2024) COVID -19 vaccines\nFebruary 2024\nRuth Link- Gelles, PhD, MPH\nCDR, US Public Health Service\nVaccine Effectiveness Program LeadCoronavirus and Other Respiratory Viruses Division\n2VE refresher\nContext for interpretation of VE\nVE against:\n–Symptomatic SARS -CoV -2, Increasing Community Access to Testing (ICATT) program\n–COVID -19-associated emergency department/urgent care encounters, VISION Network\n–COVID -19-associated hospitalizations , VISION and IVY NetworksAgenda: vaccine effectiveness (VE) of updated  2023 -24 \nCOVID -19 vaccines\n33Test\nnegative \ndesign\nVaccine effectiveness = (1 – adjusted odds ratio)*100%\nOdds of vaccination in cases\nOdds of vaccination in controlswhere odds ratio = CaseControl\nSlide adapted from Amadea Britton.Person with\nCOVID -19-like illness\nSARS -CoV-2 test\nCOVID -19\nvaccinationstatus\n44•Benefits\n•Reduces bias from health- care seeking behavior by including \ncases and controls who presented to care and received \ntesting (usually at the same facility)\n•Efficient use of an existing surveillance system\n•Considerations\n•Dependent on sensitivity and specificity of diagnostic testing \n•Controls + for another vaccine preventable disease can bias results. Sensitivity analyses dropping RSV+ and flu+ positive controls can be helpful.Test\nnegative \ndesign\nSlide adapted from Amadea Britton.\n5Efficacy and effectiveness are population level  estimates.\nAdapted from: https://www.who.int/news -room/feature- stories/detail/vaccine -efficacy -effectiveness -and -protection\nIf a vaccine has an\neffectiveness of 80 percent:\n66Context for interpreting VE across age groups\n* Internal CDC data. Data on persons aged ≥16 years is from a longitudinal, national cohort of >35,000 blood donors.High rates of SARS -CoV- 2 infection- induced immunity by July –August 2023.*\nVE findings should be interpreted as the incremental benefit  provided by COVID- 19 vaccination in a \npopulation with a high prevalence of infection- induced immunity.89%\n89%\n84%\n72%16-29 years\n30-49 years\n50-64 years\n≥65 years\n0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%\nPercent with infection- induced immunityPercent of persons with infection -induced immunity,\nbased on anti -nucleocapsid results from blood donors\n7Previously for COVID- 19 VE :\n–Absolute VE: comparing the frequency of health outcomes in vaccinated and unvaccinated \npeople\n•Example: comparing outcomes in people vaccinated with an updated  (2023 -24)  dose versus  no COVID -19 \nvaccine received ever\n–Relative VE : comparing the frequency of health outcomes in people who received one type of \nvaccine to people who received a different vaccine or by comparing people who received more \nvaccine doses to those who received fewer doses\n•Example: comparing outcomes in people vaccinated with an updated  (2023 -24)  dose versus no updated (2023 -\n24) dose\nAnalyses presented today:\n–Vaccinated group: received updated (2023 -24) dose\n–Comparison group: eligible for, but did not receive, an updated (2023 -24)  dose , regardless of past vaccination \nhistoryMeasuring updated (2023- 2024) COVID- 19 VE\n8\nUpdates to vaccine effectiveness \nagainst symptomatic infection\nIncreasing Community Access to Testing (ICATT) program\nData updated from MMWR published February 1, 2024:\nLink -Gelles R, Ciesla AA, Mak J, et al. Early Estimates of Updated 2023 –2024 (Monovalent XBB.1.5) COVID -19 Vaccine \nEffectiveness Against Symptomatic SARS -CoV -2 Infection Attributable to Co -Circulating Omicron Variants Among \nImmunocompetent Adults — Increasing Community Access to Testing Program, United States, September 2023 –January \n2024. MMWR Morb  Mortal Wkly  Rep 2024;73:77 –83. DOI: http://dx.doi.org/10.15585/mmwr.mm7304a2\n9Nationwide community -based drive- through SARS- CoV-2 testing via pharmacies\nSelf-reported vaccine history at time of registration for SARS- CoV-2 testing*\nDesign : Test -negative analysis**\nPopulation : Adults ≥18 years with ≥1 COVID -like symptom and nucleic acid amplification testing (NAAT)\nMajor exclusion criteria: Individuals with immunocompromising conditions, reported a positive SARS-\nCoV-2 test in preceding 90 days***\nPeriods for analysis:\n•Full analysis included tests from September 21, 2023 – February 18, 2024\n•Sub- analysis using SGTF**** included tests from October 27, 2023 – February 15, 2024Increasing Community Access to Testing: VE from national pharmacy testing \ndata\n*At 5% of testing encounters, COVID -19 vaccination status is collected by clinician interview\n**Odds ratios were calculated using multivariable logistic regression, adjusting for single year of age, gender, race/ethnici ty, SVI of the testing location (<0.5 versus ≥0.5), pharmacy contractor, underlying conditions (presence versus \nabsence), U.S. Department of Health and Human Services region of testing location, and date of testing\n***Additional exclusion criteria: 1) reported receiving Novavax as their most recent dose and reported receiving <2 total COV ID-19 vaccine doses; 2) reported receiving a Janssen (Johnson & Johnson) COVID -19 vaccine dose after May \n12, 2023; 3) received most recent dose <7 days prior to the date of testing or during September 1 -12, 2023; or 4) registered for  testing with a version of the questionnaire that only reported month and year of the most recent vaccine \ndose rather than calendar date.**** Results of spike gene (S -gene) amplification in real -time reverse transcription –polymerase chain reaction (RT -PCR) can be u sed to distinguish certain SARS -CoV-2 lineages over time (2). S -gene target presence (SGTP) was \ndetected in most lineages that circulated in 2023, including XBB lineages, whereas S -gene target failure (SGTF) is detected in J N.1 and other BA.2.86 lineages\nLink-Gelles, et al. MMWR 2024: http://dx.doi.org/10.15585/mmwr.mm7304a2\n (Results updated with additional month of data since publication.)\n1010ICATT: VE of 2023 -2024 COVID -19 vaccine against symptomatic infection \namong adults aged ≥18 years, by age group and time since dose\nSeptember 2023 – February 2024\nCOVID- 19 dosage pattern/age groupTotal\ntestsSARS -CoV -2-\ntest -positive,\nN (%)Median interval\nsince last dose among \nvaccinated among those \nvaccinated, days (IQR)Adjusted VE\n(95% CI)\n≥18 years\nNo updated (2023 -2024) monovalent dose (ref) 10,829 4,080 (38) 676 (427 to 859) Ref\nUpdated (2023- 2024) monovalent dose, ≥7 days 1,537 408 (27) 61 (33 to 86) 49 (42 –  55)\nUpdated (2023- 2024) monovalent dose, 7 -59 days earlier 735 170 (23) 32 (20 to 46) 55 (46 –  62)\nUpdated (2023- 2024) monovalent dose, 60- 119 days earlier 720 214 (30) 82 (71 to 95) 43 (33 –  52)\n18-49 years\nNo updated (2023 -2024) monovalent dose (ref) 8,676 3,152 (36) 691 (439 to 877) Ref\nUpdated (2023- 2024) monovalent dose, ≥7 days 943 229 (24) 61 (34 to 85) 50 (41 –  58)\nUpdated (2023- 2024) monovalent dose, 7 -59 days earlier 452 87 (19) 32 (19 to 46) 61 (50 –  69)\nUpdated (2023- 2024) monovalent dose, 60- 119 days earlier 445 130 (29) 81 (70 to 94) 39 (24 –  51)\n≥50 years\nNo updated (2023 -2024) monovalent dose (ref) 2,153 928 (43) 593 (400 to 800) Ref\nUpdated (2023- 2024) monovalent dose, ≥7 days 594 179 (30) 62 (32 to 89) 45 (32 –  55)\nUpdated (2023- 2024) monovalent dose, 7 -59 days earlier 283 83 (29) 32 (21 to 44) 43 (24 –  57)\nUpdated (2023- 2024) monovalent dose, 60- 119 days earlier 275 84 (31) 84 (72 to 98) 47 (29 –  60)\n0 20 40 60 80 100\nVaccine  Effectiveness (%)Link-Gelles, et al. MMWR 2024: http://dx.doi.org/10.15585/mmwr.mm7304a2  (Results updated with additional month of data since publication.)\n  \n11Trends in estimated proportions of SARS -CoV -2 S-gene target presence \nand variant proportions and Nowcast projections from genomic \nsurveillance\nS-gene = spike gene; SGTF = S -gene target failure; SGTP = S -gene target presence Specimen collection date (2 -week period ending)\n\n1212ICATT: VE of 2023 -2024 COVID -19 vaccine against symptomatic infection among \nadults aged ≥18 years, by S- gene target (SGT) result and time since dose\nOctober 2023 –  February  2024\nCOVID- 19 dosage pattern/age groupTotal\ntestsSARS -CoV -2 negative SARS -CoV -2 positive\nAdjusted VE\n(95% CI)No.\n(row %)Median interval \nsince last dose \namong vaccinated, \ndays (IQR) N (row %)Median interval\nsince last dose \namong vaccinated, \ndays (IQR)\nSGT presence (likely non- JN.1)\nNo updated (2023 -2024) monovalent dose (ref) 2,497 1,705 (68) 659 (403 to 820) 422 (17) 671 (405 to 801) Ref\nUpdated (2023- 2024) monovalent dose, 60- 119 days earlier 329 252 (77) 84 (72 to 98) 25 (8) 73 (69 to 83) 60 (36 to 74)\nSGT failure (likely JN.1)\nNo updated (2023 -2024) monovalent dose (ref) 2,497 1,705 (68) 659 (403 to 820) 370 (15) 682 (426 to 822) Ref\nUpdated (2023- 2024) monovalent dose, 60- 119 days earlier 329 252 (77) 84 (72 to 98) 52 (16) 86 (72 to 95) 45 (22 to 62)\n0 20 40 60 80 100\nVaccine  Effectiveness (%)\nLink-Gelles, et al. MMWR 2024: http://dx.doi.org/10.15585/mmwr.mm7304a2  (Results updated with additional month of data since publication.)\n  \n13\nVISION ED/UC\nJoint VISION/IVY MMWR to be published February 29, 2024\n1414VISION Multi -Site Network of Electronic Health Records\n369 emergency rooms and urgent cares/229 hospitals\nDesign: Test-negative analysis\nPopulation: Adults visiting a participating \nemergency department or urgent care \n(ED/UC) or hospitalized with COVID -19-like \nillness (CLI) with a SARS- CoV -2 NAAT test \nresult within 10 days before or 72 hours after encounter\n−Cases : CLI with positive  NAAT for SARS -CoV -2 and \nno positive NAAT for RSV or influenza\n–Controls : CLI with negative  NAAT for SARS -CoV-2 \nand no positive NAAT for influenza\nVaccination data: Documented by electronic health records and state \nand city registries\n1515VISION: VE of 2023 -2024 vaccine against ED/UC encounters among \nimmunocompetent adults aged ≥18 years, by age group\nSeptember 2023 – January 2024\nVE estimates adjusted for age, sex, race and ethnicity, geographic region, and calendar time. MMWR to be published February 2 9, 2024COVID- 19 dosage pattern/age groupCOVID- 19 \ncase -\npatients\nN (Col %)COVID- 19 \ncontrol -\npatients\nN (Col %)Median interval\nsince last dose among \nvaccinated among those \nvaccinated, days (IQR)Adjusted VE\n(95% CI)\n≥18 years\nNo updated (2023 -2024) monovalent dose (ref) 15,932 (92) 98,218 (88) 669 (403- 792) Ref\nUpdated (2023- 2024) monovalent dose, ≥7 days 1,297 (8) 13,378 (12) 44 (26- 64) 47 (44- 50)\nUpdated (2023- 2024) monovalent dose, 7 -59 days earlier 825 (5) 9,372 (8) 33 (20- 46) 51 (47- 54)\nUpdated (2023- 2024) monovalent dose, 60- 119 days earlier 472 (3) 4,006 (4) 74 (66- 83) 39 (33- 45)\n18-64 years\nNo updated (2023 -2024) monovalent dose (ref) 10,582 (97) 69,423 (94) 697 (480- 832) Ref \nUpdated (2023- 2024) monovalent dose, ≥7 days 377 (3) 4,739 (6) 42 (24- 62) 50 (44- 55)\nUpdated (2023- 2024) monovalent dose, 7 -59 days earlier 259 (2) 3,457 (5) 31 (19- 45) 52 (45- 58)\nUpdated (2023- 2024) monovalent dose, 60- 119 days earlier 118 (1) 1,282 (2) 73 (66- 83) 45 (34- 55)\n≥65 years\nNo updated (2023 -2024) monovalent dose (ref) 5,350 (85) 28,795 (77) 509 (362- 733) Ref \nUpdated (2023- 2024) monovalent dose, ≥7 days 920 (15) 8,639 (23) 46 (27- 66) 45 (41- 49)\nUpdated (2023- 2024) monovalent dose, 7 -59 days earlier 566 (9) 5,915 (16) 33 (21- 46) 49 (44- 54)\nUpdated (2023- 2024) monovalent dose, 60- 119 days earlier 354 (6) 2,724 (7) 74 (66- 83) 37 (29- 44)\n0 20 40 60 80 100\nVaccine  Effectiveness (%)\n16\nVISION/IVY Hospitalization\nJoint VISION/IVY MMWR to be published February 29\n1717VISION: VE of 2023 -2024 vaccine against hospitalization among \nimmunocompetent adults aged ≥18 years, by age group\nSeptember 2023 – January 2024\nVE estimates adjusted for age, sex, race and ethnicity, geographic region, and calendar time. MMWR to be published February 2 9, 2024\n*Some estimates are imprecise, which might be due to a relatively small number of persons in each level of vaccination or case  status. This imprecision indicates that the actual \nVE could be substantially different from the point estimate shown, and estimates should therefore be interpreted with caution. A dditional data accrual could increase precision \nand allow more precise interpretation.COVID- 19 dosage pattern/age groupCOVID- 19 \ncase -\npatients\nN (Col %)COVID- 19 \ncontrol -\npatients\nN (Col %)Median interval\nsince last dose among \nvaccinated among those \nvaccinated, days (IQR)Adjusted VE\n(95% CI)\n≥18 years\nNo updated (2023 -2024) monovalent dose (ref) 4,194 (91) 28,715 (87) 627 (383- 765) Ref\nUpdated (2023- 2024) monovalent dose, ≥7 days 395 (9) 4,199 (13) 42 (24- 62) 52 (47- 57)\nUpdated (2023- 2024) monovalent dose, 7 -59 days earlier 270 (6) 3,056 (9) 32 (19- 45) 53 (46- 59)\nUpdated (2023- 2024) monovalent dose, 60- 119 days earlier 125 (3) 1,143 (3) 73 (66- 81) 50 (40- 59)\n18-64 years\nNo updated (2023 -2024) monovalent dose (ref) 938 (96) 11,342 (95) 685 (447- 829) Ref\nUpdated (2023- 2024) monovalent dose, ≥7 days 38 (4) 657 (5) 38 (22- 58) 43 (20- 59)\nUpdated (2023- 2024) monovalent dose, 7 -59 days earlier 28 (3) 503 (4) 30 (19- 44) 42 (14- 61)\nUpdated (2023- 2024) monovalent dose, 60- 119 days earlier 10 (1) 154 (1) 74 (67- 81) 45 (-6-71)*\n≥65 years\nNo updated (2023 -2024) monovalent dose (ref) 3,256 (90) 17,373 (83) 549 (370- 745) Ref\nUpdated (2023- 2024) monovalent dose, ≥7 days 357 (10) 3,542 (17) 43 (25- 62) 53 (47- 58)\nUpdated (2023- 2024) monovalent dose, 7 -59 days earlier 242 (7) 2,553 (12) 32 (19- 46) 54 (47- 60)\nUpdated (2023- 2024) monovalent dose, 60- 119 days earlier 115 (3) 989 (5) 73 (66- 81) 50 (39- 59)\n0 20 40 60 80 100\nVaccine  Effectiveness (%)\n1818IVY Network —  26 hospitals, 20 U.S. States\nDesign : Case -control, prospective enrollment\nPopulation: Adults  aged  ≥18 years  hospitalized with \nAcute respiratory illness (ARI)*\n–Cases: ARI and test  positive  for SARS -CoV-2 by NAAT or \nantigen test within 10 days of illness and not positive for \ninfluenza or RSV\n–Controls : ARI and test negative  for SARS -CoV-2 and influenza \nby NAAT within 10 days of illness\nVaccination data: Electronic medical records (EMR), \nstate and city registries, and self -report\nSpecimens: Upper respiratory specimens obtained \nfor central RT -qPCR testing and sequencing\n*ARI is defined as presence of any one of the following: fever, cough, shortness of breath, chest imaging consistent with pne umo nia, hypoxemia\n1919IVY: VE of 2023 -2024 vaccine against hospitalization among \nimmunocompetent adults aged ≥18 years, by age group\nSeptember 2023 – January 2024\nSeptember 2023 – January 2024\nVE estimates adjusted for age, sex, race and ethnicity, geographic region, and calendar time. MMWR to be published February 2 9, 2024COVID- 19 dosage pattern/age groupCOVID- 19 \ncase -\npatients\nN (Col %)COVID- 19 \ncontrol -\npatients\nN (Col %)Median interval\nsince last dose among \nvaccinated among those \nvaccinated, days (IQR)Adjusted VE\n(95% CI)\n≥18 years\nNo updated (2023 -2024) monovalent dose (ref) 1100 (92) 2570 (88) 645 (387- 781) Ref\nUpdated (2023- 2024) monovalent dose, ≥7 days 94 (8) 353 (12) 47 (25- 71) 43 (27 to 56)\n≥65 years\nNo updated (2023 -2024) monovalent dose (ref) 747 (91) 1284 (84) 573 (375- 752) Ref\nUpdated (2023- 2024) monovalent dose, ≥7 days 76 (9) 245 (16) 48 (26- 72) 48 (31 to 61)\n0 20 40 60 80 100\nVaccine  Effectiveness (%)\n20Updated (2023 -2024) COVID -19 vaccination provided increased protection against \nsymptomatic SARS- CoV -2 infection and COVID -19-associated ED/UC visits and \nhospitalizations compared to no updated vaccine dose.\nReceipt of updated (2023- 2024) COVID -19 vaccine provides protection against JN.1 \nand other circulating variants\nThese are relatively early estimates from all 3 VE studies with no substantial waning; \nhowever, waning is expected,  and CDC will continue monitoring VEConclusions\n21CDC COVID -19 Vaccine Effectiveness \nand Policy Team\nAmadea Britton\nAllison Ciesla\nMonica Godfrey\nEric Griggs\nKatherine Fleming-Dutra\nDani Moulia\nMorgan Najdowski\nErica OkwuaziAnd others, including:\nSarah Ball\nJennifer DeCuir\nMonica Dickerson\nMargaret Dunne\nShikha Garg\nJefferson Jones\nAnastasia Lambrou\nPatrick Mitchell\nClint Paden\nPalak Patel\nAnd many more!!!Acknowledgements\nCaitlin Ray\nSarah Reese\nElizabeth Rowley\nPhilip Shirk\nBenjamin Silk\nZach Smith\nDiya Surie\nMark Tenforde\nZack Weber\nVISION and IVY site investigatorsJosephine Mak\nAmanda Payne\nLauren Roper\nAmi Shah\nMegan Wallace\nRyan Wiegand", "summary": "1 Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. Vaccine effectiveness of updated (2023 -2024) COVID -19 vaccines February 2024 Ruth Link- Gelles, PhD, MPH CDR, US Public Health Service Vaccine Effectiveness Program…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-28-29-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-02-28-29/04-COVID-Link-Gelles-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 21}
{"title": "05 COVID Prosser 508", "content": "Economic analysis of an \nadditional dose of COVID -19 vaccine\nUniversity of Michigan \nCOVID -19 Vaccination Modeling Team\nModel updates & additional analysis\nFebruary 2024\n1\nStudy team\nUniversity of Michigan\n•Lisa A. Prosser, PhD, Principal Investigator\n•David W. Hutton, PhD, Co -Investigator\n•Acham Gebremariam, MS, Programmer/Analyst\n•Angela Rose, MS, MPH, Project Manager\n•Kerra Mercon, MS, Research Assistant\nWake Forest University\n•Cara Janusz, PhD\nAdditional contributors to 2021 Covid Vaccination Model:\nMarisa Eisenberg, Emily Martin, Grace Chung, Janamarie \nPerroud, Ellen Kim Deluca, Chris Cadham, Huey -Fen Chen, \nAnton L.V. Avancena, Tran Doan, David SuhCenters for Disease Control and Prevention\n•Jamie Pike, PhD, Health Economist, Project officer\n•Megan Wallace, DrPH, Epidemiologist\n•Ismael Ortega -Sanchez, PhD, Senior Economist\n•Andrew Leidner, PhD, Economist\n•Fangjun Zhou, PhD, Health Scientist\n•Melisa Shah, MD, MPH, Medical Epidemiologist \n•Danielle Moulia, MPH, Health Scientist \n•Ruth Link -Gelles, PhD, Epidemiologist\n•Sharon Saydah, PhD, Epidemiologist\n2\nConflict of interest statement\n3Authors have no known conflicts of interest. \nObjectives\n•Original aims*:\noEstimate annual disease burden and healthcare utilization associated with COVID -19 \nillness and COVID -19 booster vaccination, including cases of symptomatic illness, \nhospitalizations, deaths, adverse events, costs, and quality -adjusted life years\noProject cost -effectiveness of an updated mRNA booster against COVID -19-associated \nillness in persons ages ≥18 years\n•Update s to the current version of the model: \noProbability of hospitalization: Oct 2022 -Sept 2023\noAdjusted vaccine impact: seasonality\no2-dose strategy (an additional mid -year dose)\n4* An earlier analysis from this model was presented to ACIP on September 12, 2023: Prosser, Lisa A. (2023). Economic Analysis o f Vaccination with mRNA Booster Dose \nagainst COVID -19 Among Adults.\nWeekly rates of COVID -19 associated \nhospitalizations by season, all ages\n5\n2021 -2022\nAnnual probability of hospitalization, by age\nUpdated to COVID -NET data from Oct 2022 -Sept 2023 (table)\nAge group Base caseRange\nLow High*\n18-49 y 44 10 204\n50-64 y 155 41 479\n65+ y 790 245 2090\nSource: COVID -NET05001000150020002500\n18-49 years 50-64 years 65+ yearsAnnual hospitalizations per 100,000\nSept 2023 model Updated Feb 2024 model\n6*Adjusted to include upper limit from Oct 22 -Mar 23\nNote: Table provides values for updated February 2024 model, \nreflects rates for patients hospitalized due to COVID -19 as a \nprimary diagnosis\nSeasonality -adjusted vaccine impact, 1 -dose strategy\n61%\n46%\n22%\n0%20%40%60%80%100%\n0 73 146 219 292 365Vaccine Efficacy Against Hospitalization1st dose\n020406080100120140\n1 2 3 4 5 6 7 8 9 10 11 12Hospitalizations per 100,0001st dose\nOct    Nov    Dec    Jan    Feb     Mar    Apr    May     Jun     Jul      Aug     Sep Oct    Nov    Dec    Jan    Feb     Mar    Apr    May     Jun     Jul      Aug     Sep All adults (18+ y) 65+ y only\n7Source: COVID -NET, VISION, and IVY\n02468101214161820\n1 2 3 4 5 6 7 8 9 10 11 12Critical illness\nper 100,000\n020406080100120140\n1 2 3 4 5 6 7 8 9 10 11 12Hospitalizations\nper 100,000Seasonality -adjusted vaccine impact, 1 -dose strategy, \n65+ y\n8\n1st dose\n1st doseHospitalizations                 Critical illness\nOct    Nov    Dec    Jan     Feb    Mar    Apr    May    Jun    Jul     Aug     Sep Oct    Nov    Dec    Jan     Feb    Mar    Apr    May    Jun    Jul     Aug     Sep \nSource: COVID -NET, VISION, and IVY\nSeasonality -adjusted vaccine impact, 2 -dose strategy, \n65+ y\n02468101214161820\n1 2 3 4 5 6 7 8 9 10 11 12Critical illness\nper 100,0002nd \ndose1st \ndose\n9020406080100120140\n1 2 3 4 5 6 7 8 9 10 11 12Hospitalizations\nper 100,0002nd \ndose1st \ndose\nOct    Nov    Dec    Jan     Feb    Mar    Apr    May    Jun    Jul     Aug     Sep Hospitalizations      Critical illness\nOct    Nov    Dec    Jan     Feb    Mar    Apr    May    Jun    Jul     Aug     Sep \nSource: COVID -NET, VISION, and IVY\nUpdated VE and seasonality -adjusted vaccine impact\nHealth outcomesSeptember 2023 analysis\nVEFebruary 2024 analysis*\nSeasonality -adjusted vaccine \nimpact\nAgeBase \ncaseLow High AgeBase \ncaseLow High\n1-dose\nstrategy•Symptomatic illness (non -\nhospitalized)\n•Hospitalization, uncomplicatedPooled \n18+ y 0.269 0.088 0.418 65+ y 0.347 0.134 0.468\n•Critical illness**\n•DeathPooled \n18+ y 0.403 0.191 0.671 65+ y 0.451 0.272 0.666\n2-dose\nstrategy•Symptomatic illness (non -\nhospitalized)\n•Hospitalization, uncomplicatedPooled \n18+ y 0.428 0.176 0.505 65+ y 0.434 0.179 0.509\n•Critical illness**\n•DeathPooled \n18+ y 0.552 0.382 0.672 65+ y 0.549 0.386 0.669\nSource: COVID -NET, VISION, and IVY* Updated hospitalization rates Oct 22 - Sept 23, seasonality -adjusted vaccine impact\n**Hospitalization requiring ICU and/or ventilator assistance\n10\nAdditional assumptions: 2 -dose strategy\n•Adverse events: Twice the number of the 1 -dose strategy\n•Costs of vaccination: Twice the cost of the 1 -dose strategy\n•See supplementary slides 32 -33\n11\nAnalysis Plan\n•Updated analysis : Calculate incremental cost -effectiveness ratios comparing \nupdated mRNA booster (1 -dose strategy) to no booster, using updated \nhospitalization and seasonality -adjusted vaccine impact\n•Second dose : Conduct base case and uncertainty analyses (one -way sensitivity \nand scenario analyses) comparing no booster, 1 -dose, and 2 -dose strategies\n•Project disaggregated outcomes stratified by intervention strategy and by age \nsubgroups (18 -49y, 50 -64y, 65+y) – supplemental slides\noCases\noHospitalizations\noDeaths\noCosts\noQALYs\noAdverse events\n***This presentation reports preliminary results from the second phase of an ongoing analysis***\n12\nResults\n13\nIncremental cost -effectiveness ratios (ICERs), \ncomparison to September 2023 analysis, societal \nperspective, preliminary results\nAge Intervention strategyICER\n($/QALY)\nSeptember 2023 analysisICER\n($/QALY)\nFebruary 2024 analysis\n18-49 yNo updated COVID -19 vax - -\nUpdated COVID -19 vax, 1 -dose strategy $115,588 $163,255\n50-64 yNo updated COVID -19 vax - -\nUpdated COVID -19 vax, 1 -dose strategy $25,787 $80,427\n65+ yNo updated COVID -19 vax - -\nUpdated COVID -19 vax, 1 -dose strategy Cost -saving $11,936\n14QALY = quality -adjusted life year\nIncremental cost -effectiveness ratios (ICERs), \nadding a 2 -dose strategy, societal perspective, \npreliminary results \nAge group Intervention strategyICER\n($/QALY)\n18-49 yNo updated vax -\nUpdated Covid -19 vax, 1 -dose strategy $163,255\nUpdated Covid -19 vax, 2 -dose strategy $1,317,714\n50-64yNo updated vax -\nUpdated Covid -19 vax, 1 -dose strategy $80,427\nUpdated Covid -19 vax, 2 -dose strategy $777,612\n65+ yNo updated vax -\nUpdated Covid -19 vax, 1 -dose strategy $11,936\nUpdated Covid -19 vax, 2 -dose strategy $255,122\n15QALY = quality -adjusted life year\nICERs, 1 -way sensitivity analysis, \nprobability of hospitalization, societal perspective, \npreliminary results\n*Probability of hospitalization inputs, base case (range):  18-49 y: 0.000443 (0.000101 - 0.00204); 50 -64 y: 0.00155 (0.000413 - 0.00479); \n65+ y: 0.0079 (0.00245 - 0.0209)\nICER = incremental cost -effectiveness ratio; QALY = quality -adjusted life yearAge \ngroupStrategyICER ($/QALY)\nBase case Lower bound Upper bound\n18-49 yUpdated Covid -19 vax, 1 -dose strategy $163,255 $195,442 $69,538\nUpdated Covid -19 vax, 2 -dose strategy $1,317,714 $1,507,831 $807,114\n50-64 yUpdated Covid -19 vax, 1 -dose strategy $80,427 $161,605 Cost saving\nUpdated Covid -19 vax, 2 -dose strategy $777,612 $1,193,501 $349,971\n65+ yUpdated Covid -19 vax, 1 -dose strategy $11,936 $81,544 Cost saving\nUpdated Covid -19 vax, 2 -dose strategy $255,122 $566,141 $80,182\n16\nAlternative season scenarios\n17050100150200250300\nOct\nNov\nDec\nJan\nFeb\nMar\nApr\nMay\nJune\nJuly\nAug\nSeptHospitalizations per 100,000\n18-49 50-64 65+050100150200250300\nOct\nNov\nDec\nJan\nFeb\nMar\nApr\nMay\nJune\nJuly\nAug\nSeptHospitalizations per 100,000\n18-49 50-64 65+Alternative season #2 \n(spring peak)\n050100150200250300\nOct\nNov\nDec\nJan\nFeb\nMar\nApr\nMay\nJun\nJul\nAug\nSepHospitalizations per 100,000\n18-49 50-64 65+Alternative season #1 \n(winter peak)Base case\n050100150200250300\n1 2 3 4 5 6 7 8 9 10 11 12Hospitalizations\nper 100,0001st doseSeasonality -adjusted vaccine impact: \nalternative season scenario #1 (winter peak)\nHealth outcomes Age groupSeasonality -adjusted vaccine impact, alternative scenario #1 (winter peak)\n1-dose 2-dose\nBase Lower Upper Base Lower Upper\nSymptomatic illness and \nhospitalization65+ years0.334 0.121 0.460 0.443 0.181 0.516\nCritical care and death 0.432 0.229 0.657 0.540 0.379 0.660\n18\n2nd dose\nOct Nov Dec Jan Feb Mar  Apr  May  Jun  Jul Aug Sep \n\n050100150200250300\n1 2 3 4 5 6 7 8 9 10 11 12Hospitalizations\nper 100,0001st doseSeasonality -adjusted vaccine impact: \nalternative season scenario #2 (spring peak)\nHealth outcomes Age groupSeasonality -adjusted vaccine impact, alternative scenario #2 (spring peak)\n1-dose 2-dose\nBase Low High Base Low High\nSymptomatic illness and \nhospitalization65+ years0.269 0.070 0.401 0.439 0.194 0.514\nCritical care and death 0.444 0.190 0.670 0.571 0.410 0.688\n19050100150200250300\nOct Nov Dec Jan Feb Mar Apr May June July Aug Sept\n18-49 50-64 65+\n2nd dose\nOct Nov Dec Jan Feb Mar Apr  May Jun  Jul  Aug  Sep \n\nICERs, scenario analysis varying seasonality, societal \nperspective, preliminary results\n20Age \ngroupIntervention strategyBase case ICER\n$/QALYAlternative season #1\n(winter peak)\nICER ($/QALY)Alternative season #2\n(spring peak)\nICER ($/QALY)\n65+ yUpdated Covid -19 vax, 1 -dose strategy $11,936 $14,788 $25,126\nUpdated Covid -19 vax, 2 -dose strategy $255,122 $198,802 $115,650\nICER = incremental cost -effectiveness ratio; QALY = quality -adjusted life year\nICER, scenario analysis varying probability of \nhospitalization*, age 65+, societal perspective, \npreliminary results\n21Intervention strategyICER ($/QALY)\n¼ base case\n(198 per 100,000)½ base case\n(395 per 100,000)Base case\n(790 per 100,000)2x base case\n(1580 per 100,000)3x base case\n(2370 per 100,000)4x base case\n(3160 per 100,000)\nUpdated Covid -19 vax, 1 -dose $93,904 $52,541 $11,936 Cost saving Cost saving Cost saving\nUpdated Covid -19 vax, 2 -dose $624,028 $433,533 $255,122 $120,341 $64,599 $34,133\n*Adjusted risk of hospitalization by underlying condition: chronic obstructive pulmonary disease: 0.9, history of stroke: 0.9 , coronary artery \ndisease: 1.3, asthma: 1.4, hypertension: 2.8, obesity: 2.9, diabetes: 3.2, chronic kidney disease: 4.0, severe obesity: 4.4. Ko et al 2021.\nICER = incremental cost -effectiveness ratio; QALY = quality -adjusted life year\nICER, scenario analyses varying vaccination costs, \nage 65+, societal perspective, preliminary results\nIntervention strategyICER ($/QALY)\n$20 $60 Base case $120\nUpdated Covid -19 vax, 1 -dose strategy Cost saving Cost saving $11,936\nUpdated Covid -19 vax, 2 -dose strategy $72,240 $145,393 $255,122\nIntervention strategyICER ($/QALY)\nAll lower Base case All upper\nUpdated Covid -19 vax, 1 -dose strategy Cost saving $11,936 $53,251\nUpdated Covid -19 vax, 2 -dose strategy $50,768 $255,122 $443,059Varying vaccine dose cost only\nVarying all vaccination -related costs*\n22*Multi -way sensitivity analysis varying vaccine dose cost, vaccine administration cost, time costs of vaccination, and cost of  \nvaccine -associated adverse events to lower and upper bounds. See supplementary slides 32 -33 for input data.\nICER = incremental  cost-effectiveness ratio; QALY = quality -adjusted life year\nLimitations\n•Unpublished data used to derive key parameters in the model: vaccine effectiveness, \nsymptomatic illness, probabilities of hospitalization and critical illness\n•Data sources vary in representativeness, generalizability\n•VE estimates derived from data on bivalent booster \n•Few seasons to date to estimate seasonality\n•MarketScan  data for ages 65+ only includes those with supplemental insurance\n•Evidence base for long covid is especially scarce\n•Model does not include reduced transmission (conservative approach) \n23\nSummary\n•1-dose strategy, updated inputs (hospitalization, seasonality -adjusted VE)\n➢Vaccination averts substantial morbidity and mortality as demonstrated through \nestimated disaggregated outcomes (supplementary slides)\n➢ICERs for 50 -64y and 65+ age groups remain robust to changes in parameter inputs \nacross plausible ranges (with a few exceptions)\n➢ICERs for 18 -49y remain sensitive to changes in parameter inputs; more favorable for \nhigher VE, higher risk of hospitalization, and critical illness\n•2-dose strategy\n➢Not economically favorable for 18 -49y or 50 -64y across plausible parameter ranges\n➢For 65+ years, ICERs are sensitive to probability of hospitalization, costs, and \nseasonality\n➢ICERs are more favorable in scenarios with higher risk of hospitalization, lower costs, \nand alternate seasonality\n24", "summary": "Economic analysis of an  additional dose of COVID -19 vaccine University of Michigan  COVID -19 Vaccination Modeling Team Model updates & additional analysis February 2024 1 Study team University of Michigan •Lisa A. Prosser, PhD, Principal Investigator •David W. Hutton, PhD, Co -Investigator •Acham Gebremariam, MS, Programmer/Analyst •Angela Rose, MS, MPH, Project Manager •Kerra Mercon, MS, Research Assistant Wake Forest University •Cara Janusz, PhD Additional contributors to 2021 Covid…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-28-29-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-02-28-29/05-COVID-Prosser-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 24}
{"title": "06 COVID Wallace 508", "content": "Centers for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nEvidence to Recommendations Framework:\nAdditional Dose of 2023-2024 Formula COVID -19 Vaccine in Older Adults \nMegan Wallace, DrPH, MPH\nACIP Meeting February 28, 2024\nShould persons ages 65 years and older be recommended for an additional dose of \n2023- 2024 Formula COVID -19 vaccine? \n–Additional dose should be at least 4 months after previous updated (2023 -2024) \nCOVID -19 vaccine dose. \nAuthorized and approved 2023 -2024 Formula COVID -19 vaccines:\n–Moderna COVID -19 vaccine ​\n–Novavax COVID -19 vaccine\n–Pfizer -BioNTech COVID -19 vaccineEvidence to Recommendations (EtR) Framework\nPolicy Question\n2\n3Timeline of additional dose recommendations \nSept – Nov 2021 COVID -19 vaccine \nbooster doses \nrecommended \nfor persons ages \n≥18 years\nMay 2022 Additional COVID -19 \nvaccine booster dose \nrecommended for \npersons ages ≥50 years\n(should  recommendation)\nSept – Oct 2022 Bivalent COVID -19 \nvaccine dose \nrecommended for \npersons ages ≥5 \nyears\nApril 2023 Optional additional \nbivalent COVID -19 \nvaccine dose \nrecommended for \npersons ages ≥65 years\n(may  recommendation)\nSept 20232023- 2024 COVID -\n19 vaccine doses \nrecommended for \npersons ages ≥6 \nmonths\nPeople who are moderately or severely immunocompromised:\nHave the option to receive 1 additional dose of updated (2023 -2024 Formula) COVID -\n19 Vaccine at least 2 months following the last recommended updated (2023 -2024 \nFormula) COVID -19 vaccine dose.\nFurther additional dose(s) may be administered, informed by the clinical judgement of \na healthcare provider and personal preference and circumstances. Any further additional doses should be administered at least 2 months after the last updated (2023- 2024 Formula) COVID -19 vaccine dose.Current recommendations for additional doses of updated \n(2023 -2024 Formula) COVID- 19 vaccine\nNote: Children aged 6 months –4 years need multiple doses of COVID -19 vaccines to be up to date, including at least 1 dose of updated COVID -19 vaccine. 4\nEtR Domain:\nPublic Health Problem \n\n66Weekly number of COVID -19 hospitalizations, United States,\nJanuary 1, 2023 – February 17, 2024\nCDC COVID Data Tracker. National Healthcare Safety Network (NHSN). https://covid.cdc.gov/covid -data -tracker/#trends_weeklyhospitaladmissions_select_00 . Accessed February \n23, 2024\n\n77Weekly population -based rates of COVID -19-associated \nhospitalizations, by age group  —  COVID -NET , January 1, 2023 – \nFebruary 24, 2024\nDashed lines indicate potential reporting delays and interpretation of trends should exclude these weeks.\nCDC COVID Data Tracker. https://covid.cdc.gov/covid -data -tracker/#covidnet -hospitalization -network . Accessed February 23, 2024\n\n88Weekly population- based rates of COVID -19-associated \nhospitalization among adults ages ≥65 years, by age group— \nCOVID -NET, January 1, 2023 – January 27, 2024\nThin dashed lines on the far right indicate potential reporting delays and interpretation of trends should exclude these week s. \nCDC COVID Data Tracker. https://covid.cdc.gov/covid -data -tracker/#covidnet -hospitalization -network . Accessed February 6, 2024\n\n99Weekly number of provisional COVID -19 deaths reported to \nCDC, United States, January 1, 2023 – February 17, 2024\nThe most recent 3 weeks of mortality counts are shaded grey because NVSS reporting is <95% during this period.\nProvisional data are non -final counts of deaths based on reported mortality data in NVSS. Deaths include those with COVID- 19, coded as ICD– 10 code U07.1, on the death certificate. \nDeath data are displayed by date of death (event).\nCDC COVID Data Tracker. National Center for Health Statistics (NCHS) National Vital Statistics System (NVSS). https://covid.cdc.gov/covid- data -tracker/#trends_weeklydeaths_select_00 . \nAccessed February 23, 2024\n\n1010Monthly rates of provisional COVID -19 deaths by age group, \nUnited States, January 1, 2023 – January 31, 2024\nProvisional data are non -final counts of deaths based on reported mortality data in NVSS. Deaths include those with COVID- 19, coded as ICD– 10 code U07.1, on the death certificate. \nDeath data are displayed by date of death (event).\nSource: Provisional data from the CDC’s National Center for Health Statistics (NCHS) National Vital Statistic System (NVSS); CDC COVID Data Tracker. https://covid.cdc.gov/covid- data -\ntracker/#demographicsovertime . Accessed February 23, 2024\n\n1111Weighted U.S. SARS -CoV-2 seroprevalence by vaccine and \ninfection history and age, based on blood donations\nSeroprevalence definition: The percentage of people with antibodies against a virus in their blood is known as seroprevalence . \nMethodology available at https://covid.cdc.gov/covid- data -tracker/#nationwide -blood -donor -seroprevalence -2022 9\n14\n2635\n26\n1454\n59\n581\n2\n2\n0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%30 to 49 years\n50 to 64 years\n65 years and olderJuly 1st – September 30th, 2023\nVaccination-only seroprevalence Infection-only seroprevalence\nHybrid Immunity Neither past infection nor vaccination\n1212Pool of naïve T cells diminishes with age\nSource: de Candia P , Prattichizzo  F, Garavelli S, Matarese G. T Cells: Warriors of SARS- CoV-2 Infection. Trends Immunol. 2021 Jan;42(1):18- 30. doi: 10.1016/j.it.2020.11.002. \nEpub 2020 Nov 13. PMID: 33277181; PMCID: PMC7664351Immunosenescence  refers to  age-associated immune decline that may result in an inefficient immune response to \nnovel antigens and an inability to develop proper immunity against infections and upon vaccination.\n1313Adaptive immunity includes cellular and humoral responses\nSource: Rey, Gertrud.  T Cell Responses to Coronavirus Infection are Complicated. https://www.virology.ws/2020/11/05/t -cell-responses -to-coronavirus -infection -are-complicated/Insufficient pools of naïve T \ncells impacts ability to generate:\n•Neutralizing antibody responses \n•Cytotoxic T cells\n1414Weekly percent of tests positive for COVID -19, Influenza, and \nRSV, United States, October 1, 2022 – February 17, 2024\nPreliminary data are shaded in gray.\nSources: COVID -19 and RSV: National Respiratory and Enteric Virus Surveillance System (NREVSS), a sentinel network of laboratori es located through the US, includes clinical, public health \nand commercial laboratories; additional information available at: https://www.cdc.gov/surveillance/nrevss/index.html. Influen za: Clinical laboratory test results from NREVSS and U.S. World \nHealth Organization collaborating laboratories; more details about influenza virologic surveillance are available here: https:// www.cdc.gov/flu/weekly/overview.htm.\nCDC Respiratory Virus Activity Levels. https://www.cdc.gov/respiratory -viruses/data -research/dashboard/activity -levels.html . Accessed February 6, 2024\n\n1515\nWeekly hospitalization rate per 100,000 population, United \nStates, October 1, 2022 – February 17, 2024 \nPreliminary data are shaded in gray.\nDashed line represents the nadir for COVID- 19 hospitalization rates.\nCDC Respiratory Virus Activity Levels. National Healthcare Safety Network. https://www.cdc.gov/respiratory -viruses/data -research/dashboard/illness -severity.html. Accessed \nFebruary 23, 2024\n\nDomain Equity Question:\nDoes the problem impact all populations equally?\n\n1717Age-adjusted cumulative COVID -19 hospitalizations per 100,000 \npopulation by race and ethnicity  — COVID -NET , October 2022 – \nSeptember 2023\nCDC COVID Data Tracker. https://covid.cdc.gov/covid -data -tracker/#covidnet -hospitalization -network . Accessed February 23, 2024\n\n1818Number of chronic conditions by age among Asian, Black, Latino/Hispanic, \nand White adults in the National Health Interview Survey, 1999 to 2018 \nSource: Caraballo C, Herrin J, \nMahajan S, et al. Temporal Trends in \nRacial and Ethnic Disparities in Multimorbidity Prevalence in the United States, 1999 -2018. Am J Med . \n2022;135(9):1083- 1092.e14. \ndoi:10.1016/j.amjmed.2022.04.010   \n\nCOVID -19 hospitalizations peaked in late December/early January, however there are still \napproximately 20,000 new hospital admissions and 2,000 deaths due to COVID -19 each week.\nPersons ages ≥65 years have the highest COVID -19 hospitalization rates.\n–Hospitalization rates within this age group increase with increasing age.\nPersons ages ≥75 years have the highest COVID -19 mortality rates.\nImmunosenescence and higher prevalence of vaccine-only immunity in older adults compared \nto younger adults suggest that more frequent doses may be needed to maintain protection in \nthis population.\nWhile there are increases in COVID -19 during respiratory virus season, COVID -19 \nhospitalizations and deaths continue throughout the year due to ongoing circulation of SARS -\nCoV-2.\nInequities in COVID -19 hospitalizations by race and ethnicity continue and should be \nconsidered in the context of an age-based recommendation.Summary \nPublic Health Problem \n19\nPublic Health Problem\nWork Group Interpretation\nIs COVID -19 disease among persons ages 65 years and older of public health \nimportance?\noNooProbably no oProbably yes oYesoVaries oDon’t know\nEtR Domain:\nBenefits and Harms \n\nUpdated (2023- 2024) COVID -19 vaccination provided increased protection against \nsymptomatic SARS- CoV- 2 infection and COVID -19-associated ED/UC visits and \nhospitalizations compared to no updated vaccine dose.\nReceipt of updated (2023 -2024) COVID -19 vaccine provides protection against JN.1 and \nother circulating variants.\nThese early vaccine effectiveness estimates show no substantial waning; however, \nwaning is expected.2023 -2024 Formula COVID- 19 vaccine effectiveness\nED: Emergency department | UC: Urgent care 22\n23VISION: Absolute  VE of original  monovalent  and bivalent  booster doses \nagainst hospitalization among immuno competent  adults, by age group – \nSeptember 2022 – August 2023\nVE estimates adjusted for age, sex, race and ethnicity, geographic region, and calendar time. Updated from: Link -Gelles et al., MMWR, https://www.cdc.gov/mmwr/volumes/72/wr/mm7221a3.htm  \n* These estimates are imprecise, which might be due to there being a relatively small number of persons in each level of vacc ination or case status. This imprecision indicates that the actual VE \ncould be substantially different from the point estimate shown, and estimates should therefore be interpreted with caution. A dditional data accrual could increase precision and allow more precise \ninterpretation.mRNA Dosage PatternTotal\ntestsSARS -CoV -2-\ntest -positive,\nN (%)Median interval\nsince last dose,\ndays (IQR)Adjusted VE\n(95% CI)\n18-64 years\nUnvaccinated (ref) 13,089 803 (6) -- Ref\nOriginal monovalent  doses only 19,799 1,129 (6) 455 (333 -575) 15 (6 to 23)\nBivalent  booster, 7 -59 days earlier 1,208 45 (4) 33 (21 -45) 61 (46 to 71)\nBivalent  booster, 60- 119 days earlier 1,248 87 (7) 87 (73 -102) 15 (-8 to 33)\nBivalent  booster, 120- 179 days earlier 1,075 59 (6) 147 (134 -163) -1 (-35 to 24)*\n≥65 years\nUnvaccinated (ref) 12,015 1,688 (14) -- Ref\nOriginal monovalent  doses only 37,001 4,216 (11) 402 (288 -555) 25 (20 -30)\nBivalent  booster, 7 -59 days earlier 4,607 328 (7) 35 (21- 48) 67 (62 -71)\nBivalent  booster, 60- 119 days earlier 5,252 490 (9) 88 (73 -104) 53 (48 -58)\nBivalent  booster, 120- 179 days earlier 4,482 415 (9) 149 (134 -164) 28 (18 -36)\n-40 -20 0 20 40 60 80 100\nVaccine  Effectiveness (%)\n24VISION: Absolute  VE of original  monovalent  and bivalent  booster doses \nagainst hospitalization and critical illness among immuno competent  adults \naged ≥18 years – September 2022 – August 2023\nCritical illness defined as admission to intensive care unit or death; case -patients were persons admitted to ICU or who experie nced death associated with COVID -19, and control \npatients were persons hospitalized without COVID -19. VE estimates adjusted for age, sex, race and ethnicity, geographic region, and calendar time. Updated from: Link -Gelles et \nal., MMWR, https://www.cdc.gov/mmwr/volumes/72/wr/mm7221a3.htm  mRNA Dosage PatternTotal\ntestsSARS -CoV -2-\ntest -positive,\nN (%)Median interval\nsince last dose,\ndays (IQR)Adjusted VE\n(95% CI)\nHospitalization\nUnvaccinated (ref) 25,104 2,491 (10) -- Ref\nOriginal monovalent  doses only 56,800 5,345 (9) 420 (306 -563) 22 (17- 26)\nBivalent  booster, 7 -59 days earlier 5,815 373 (6) 34 (21 -47) 65 (61 -69)\nBivalent  booster, 60- 119 days earlier 6,500 577 (9) 87 (73 -103) 48 (42 -53)\nBivalent  booster, 120- 179 days earlier 5,557 474 (9) 149 (134 -164) 22 (13- 30)\nCritical illness\nUnvaccinated (ref) 23,140 527 (2) -- Ref\nOriginal monovalent  doses only 52,352 897 (2) 422 (306 -564) 32 (23- 40)\nBivalent  booster, 7 -59 days earlier 5,504 62 (1) 34 (21 -47) 69 (59 -77)\nBivalent  booster, 60- 119 days earlier 6,023 100 (2) 87 (73 -103) 50 (36 -60)\nBivalent  booster, 120- 179 days earlier 5,144 61 (1) 149 (134 -164) 46 (28 -60)\n-20 0 20 40 60 80 100\nVaccine  Effectiveness (%)\nNo clinical trial immunogenicity data of an additional dose of 2023 -2024 COVID -19 vaccine.\nInitial dose of 2023 -2024 COVID -19 vaccine elicits robust neutralizing antibodies and provides \nprotection against JN.1 and other circulating variants.1,2\nEffectiveness of an additional dose in older adults has been demonstrated by past additional \ndoses\n–Among adults aged ≥50 years eligible to receive a second original monovalent mRNA COVID- 19 \nvaccine booster dose, VE for COVID- 19–associated ED/UC encounters during the BA.2/BA.2.12.1 \nperiod was 32% at ≥120 days after the third dose but increased to 66% ≥7 days after the fourth dose. \nVE against COVID -19–associated hospitalization was 55% ≥120 days after the third dose but increased \nto 80% ≥7 days after the fourth dose.3\n–In a large cohort of nursing home residents, r eceipt of a second original monovalent mRNA COVID -19 \nbooster dose during circulation of SARS- CoV-2 Omicron subvariants was 74% effective at 60 days \nagainst severe COVID -19–related outcomes (including hospitalization or death) and 90% against death \nalone compared with receipt of a single booster dose.4Effectiveness of an additional dose of COVID -19 vaccine\n1.https://www.biorxiv.org/content/10.1101/2023.11.26.568730v2\n2.https://www.cdc.gov/mmwr/volumes/73/wr/mm7304a2.htm  \n3.https://www.cdc.gov/mmwr/volumes/71/wr/mm7129e1.htm  \n4.https://www.cdc.gov/mmwr/volumes/71/wr/mm7139a2.htm  25\n26Microsimulation modeling study compares frequency of \nCOVID -19 vaccine by risk group\nhttps://www.medrxiv.org/content/10.1101/2023.07.10.23292473v4  \nHJ Park…NC Lo. Accepted at Nature Communications (2024) .Step 1 : Assign to risk group\n•Age group: 18-49, 50- 64, 65- 74, 75+ years\n•Immune status: immunocompetent, \nimmunocompromised (mild, moderate/severe)Step 3 : Calibrate model to data\n•Epidemiologic data: COVID -19 severe incidence, seroprevalence\n•Calibrated to ~September 2022\nComputer \nsimulation\nStep 2 : Simulate vaccine -induced or hybrid protection\n•Vaccine: number doses, timing of last dose\n•Prior infection: yes/no, timing of last infection\n•Vaccine/hybrid protection data: level of protection and waning curves Step 4 : Run simulation of different vaccine strategies\n•Vaccine strategies: One -time (1 dose); Annual (2 doses), Semi -annual (4 \ndoses); Simulate over 2 -years\n•Simulate person- level waning of protection and COVID -19 at each time step \n(static infection model)\n•Primary study outcome: Absolute annual risk of severe COVID -19\n3 Month \n06 1\n\n27Annual and semiannual COVID -19 vaccine doses likely to have largest benefit \nin people ages ≥65 years and people who are immunocompromised\nAbsolute annual risk of \nsevere COVID -19  \n(cases per 100,000; \nuncertainty interval)Annual risk reduction of severe \nCOVID -19 NNT to avert \nsevere \nCOVID -19 case Absolute risk (cases \nper 100,000)Relative risk \n(%)\nOne -time booster\n18-49 years 98 (85 -  125) -- -- --\n50-64 years 199 (185 -  238) -- -- --\n65-74 years 524 (499 -  562) -- -- --\n75+ years 1,398 (1,332 -  1,501) -- -- --\nImmunocompromised (mild) 1,290 (1,205 –  1,403) -- -- --\nImmunocompromised (moderate/severe) 1,367 (1,266- 1,503) -- -- --\nAnnual booster\n18-49 years 84 (74 -  106) 14 14% 3,534\n50-64 years 171 (159 -  202) 28 14% 1,806\n65-74 years 446 (425 -  475) 78 15% 642\n75+ years 1,198 (1,144 -  1,272) 199 14% 251\nImmunocompromised (mild) 1,180 (1,088 -  1,316) 110 9% 456\nImmunocompromised (moderate/severe) 1,183 (1,091- 1,307) 184 13% 273\nSemiannual booster (every 6 months)\n18-49 years 72 (64 -  90) 26 27% 1,916\n50-64 years 147 (136 -  171) 52 26% 968\n65-74 years 382 (365- 404) 142 27% 353\n75+ years 1,030 (988 -  1,088) 368 26% 136\nImmunocompromised (mild) 1,095 (987 -  1,255) 195 15% 257\nImmunocompromised (moderate/severe) 1,057 (966- 1,183) 310 23% 162\nhttps://www.medrxiv.org/content/10.1101/2023.07.10.23292473v4  \nHJ Park…NC Lo. Accepted at Nature Communications (2024) .NNT: number of persons needed to follow vaccine strategy \nto prevent one severe COVID -19 case over 2- year period\nSevere COVID -19 case: defined as being hospitalized\n28COVID -19 vaccines have a favorable safety profile as demonstrated by robust safety \nsurveillance over 3 years of COVID -19 vaccine use.\n–Anaphylactic reactions have been rarely reported following receipt of COVID -19 vaccines.\n–Rare risk of myocarditis and pericarditis, however this is predominately in males ages 12 -39 \nyears.  \n–No new safety concerns have been identified for the 2023 -2024 Formula COVID -19 vaccine.\nReactogenicity symptoms have been reported following COVID -19 vaccines.\n–Local: Pain at the injection site; less commonly, redness and swelling at the injection site\n–Systemic: Fever, fatigue, headache, chills, myalgia, arthralgia, and diarrhea\n–Overall, symptoms less frequent and severe among older adults compared with adolescents \nand younger adults.COVID -19 vaccine safety\n29A statistical signal for ischemic stroke after Pfizer- BioNTech bivalent mRNA COVID -19 \nvaccine was detected in CDC’s Vaccine Safety Datalink in persons aged ≥65 years during \nfall 2022; information was presented at prior ACIP meetings and efforts have been underway to evaluate the signal.\n2\nAvailable data do not provide clear and consistent evidence of a safety problem for ischemic stroke with bivalent mRNA COVID -19 vaccines when given alone or given \nsimultaneously with influenza vaccines.\n–Variable and inconsistent results were obtained in some analyses of the risk of ischemic \nstroke following bivalent mRNA COVID -19 vaccination, simultaneous bivalent mRNA COVID -\n19 and influenza vaccination, and influenza vaccination alone.\n–Most study results have not shown an association between vaccination and ischemic stroke, and no clear pattern demonstrating increased risk has emerged.Review of COVID -19 vaccine and ischemic stroke1\n1https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2023- 10-25-26/01- VaxSafety -Shimabukuro -508.pdf  \n2 https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2023- 02/slides -02-24/COVID -02-Shimabukuro -508.pdf  and\nhttps://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2023- 04-19/03- COVID -Shimabukuro -508.pdf  \n30Any real or theoretical risk needs to be placed in the context of the known benefits of \nCOVID -19 vaccination in preventing COVID- 19 disease and the potentially serious \ncomplications, including stroke.\nAmong adults aged ≥65 years, a recent bivalent mRNA COVID -19 vaccine dose helped \nprovide protection against COVID- 19-related thromboembolic events compared with \nmore distant receipt of original monovalent doses alone.1Review of COVID -19 vaccine and ischemic stroke\n1. https://www.cdc.gov/mmwr/volumes/73/wr/mm7301a4.htm  \nDomain Equity Question:\nAre the desirable and undesirable anticipated effects \ndemonstrated across all populations equally?\n\nThere is no evidence to suggest that COVID- 19 vaccine effectiveness varies substantially \nby race/ethnicity.1,2\n–Differences in vaccine hesitancy/uptake, crowding, access to care, and prior infection could \nimpact vaccine effectiveness and these factors may also differ by race/ethnicity. \nThere is no evidence to suggest that COVID- 19 vaccine safety profiles vary by \nrace/ethnicity, however risk has been shown to differ by age and sex.\n–Risk for myocarditis is highest in adolescent and young adult males.\nBenefits and harms for the U.S. population are best assessed when clinical trial and \nstudy populations are optimally representative of the U.S. population. Are the desirable and undesirable anticipated effects \ndemonstrated across all populations equally?\n1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9619452/  \n2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9763212/  32\n2023-2024 Formula COVID -19 vaccination provided increased protection against symptomatic \nSARS -CoV -2 infection and COVID -19-associated ED/UC visits and hospitalizations compared to \nno updated vaccine dose.\n–COVID -19 vaccine effectiveness from previous vaccine formulations has waned over time but \nappears more durable against critical illness.\nAn additional dose of 2023 -2024 Formula may restore vaccine effectiveness which is expected \nto wane, providing additional protection until the next updated vaccine is available.\nCOVID -19 vaccines have a favorable safety profile.\n–Local and systemic symptoms have been reported following receipt of COVID -19 vaccines; \nhowever, symptoms are less frequent and severe among older adults compared with \nadolescents and younger adults.\n–Available data do not provide clear and consistent evidence of a safety issue for ischemic \nstroke with bivalent mRNA COVID -19 vaccines either when given alone or given \nsimultaneously with influenza vaccines.Summary\nBenefits and Harms \n33\nBenefits and Harms \nHow substantial are the desirable anticipated effects?\n•How substantial are the anticipated effects for each main outcome for which \nthere is a desirable effect?\noMinimal oSmall oModerate oLarge oVaries oDon’t know\nBenefits and Harms \nHow substantial are the undesirable anticipated effects?\n•How substantial are the anticipated effects for each main outcome for which \nthere is an undesirable effect?\noMinimal oSmall oModerate oLarge oVaries oDon’t know\nMinority opinion  Majority opinion  \nBenefits and Harms \nDo the desirable effects outweigh the undesirable effects?\n•What is the balance between the desirable effects relative to the \nundesirable effects?\noFavors intervention (Additional dose of 2023-2024 Formula COVID -19 vaccine)\noFavors comparison (no vaccine)\noFavors both\noFavors neither\noUnclear\nEtR Domain:\nValues \n\n3838Key attitudes and experiences among adults 18 years and older, December 2023\nNational Immunization Survey -Adult COVID Module (NIS -ACM)\nThe December estimates are based on data collected November 26 through December 30.\nCDC. COVID -19 Vaccination Coverage and Vaccine Confidence Among Adults. https://www.cdc.gov/vaccines/imz -managers/coverage/covidvaxview/interactive/adults.html  \nAccessed February 7, 2024COVID -19 Vaccination Key Attitudes and Experiences by Age Group \nAmong Adults Age ≥18 Years, NIS -ACM, December 2023\nAdults ages 65 years and older were more \nconcerned about COVID -19 disease and had \nhigher confidence in vaccine safety and \nvaccine importance; those ages 18 – 49 years \nand 50 – 64 years were less concerned and \nconfident.265365\n355367\n416578\n0102030405060708090\nConcerned about COVID-19 disease Confidence in COVID-19 vaccine safety Confidence that COVID-19 vaccine is\nsomewhat or very important to protect\nmePercent\n18 - 49 years 50 - 64 years 65+ years\n3939Half of adults say they are taking precautions because of \nCOVID -19 during the fall and winter months \nThe survey was conducted October 31 - November 7, 2023, online and by telephone among a nationally representative sample of 1,301  U.S. adults.\nKFF COVID -19 Vaccine Monitor (Oct. 31- Nov. 7, 2023) KFF COVID -19 Vaccine Monitor November 2023: With COVID Concerns Lagging, Most People Have Not Gotten Latest Vaccine \nAnd Half Say They Are Not Taking Precautions This Holiday Season | KFF  Accessed November 17, 2023501819253035\n0 10 20 30 40 50 60 70 80 90 100Any of these precautionsTaking a COVID-19 test before visiting with friends or familyAvoiding dining indoors at restaurantsAvoiding travelWearing a mask in crowded placesAvoiding large gatherings\nPercentPercent who say they are taking each of the following precautions because of \nCOVID -19 this fall and winter:\n40Similar shares of younger and older adults reported plans to take at least one \nprecaution during the fall and winter.\nHowever, four in ten ( 41% ) adults ages 65 and older said they plan to avoid large \ngatherings, compared to a third ( 33% ) of those under the age of 65.\nWhile younger adults were less likely to say they will avoid large gatherings, 21%  of \nthose <65 years say they will take a test for COVID -19 before spending time with friends \nor family compared to 10%  of those ages 65 and older.Precautions against COVID -19 during fall and winter by age \nThe survey was conducted October 31 - November 7, 2023, online and by telephone among a nationally representative sample of 1,301  U.S. adults.\nKFF COVID -19 Vaccine Monitor (Oct. 31- Nov. 7, 2023) KFF COVID -19 Vaccine Monitor November 2023: With COVID Concerns Lagging, Most People Have Not Gotten Latest Vaccine \nAnd Half Say They Are Not Taking Precautions This Holiday Season | KFF  Accessed November 17, 2023\nDomain Equity Question:\nIs there important variability in how patients or \npopulations value the outcome?\n\n4242Key attitudes and experiences among adults 18 years and older, December 2023\nNational Immunization Survey -Adult COVID Module (NIS -ACM)\nAI/AN: American Indian or Alaska Native; NH/PI: Native Hawaiian or Other Pacific Islander\nThe December estimates are based on data collected November 26 through December 30.\nCDC. COVID -19 Vaccination Coverage and Vaccine Confidence Among Adults. https://www.cdc.gov/vaccines/imz -managers/coverage/covidvaxview/interactive/adults.html  \nAccessed February 7, 2024COVID -19 Vaccination Key Attitudes and Experiences by Race & Ethnicity \nAmong Adults Age ≥18 Years, NIS -ACM, December 2023\n295573\n305765\n415078\n347185\n334967\n313354\n304757\n0102030405060708090\nConcerned about COVID-19 disease Confidence in COVID-19 vaccine safety Confidence that COVID-19 vaccine is\nsomewhat or very important to protect\nmePercent\nHispanic White, non-Hispanic Black, non-Hispanic\nAsian, non-Hispanic NH/PI, non-Hispanic AI/AN, non-Hispanic\nOther or multiple races, non-Hispanic\n4343Precautions against COVID -19 during fall and winter by race \nand ethnicity \nThe survey was conducted October 31 - November 7, 2023, online and by telephone among a nationally representative sample of 1,301  U.S. adults.\nKFF COVID -19 Vaccine Monitor (Oct. 31- Nov. 7, 2023) KFF COVID -19 Vaccine Monitor November 2023: With COVID Concerns Lagging, Most People Have Not Gotten Latest Vaccine \nAnd Half Say They Are Not Taking Precautions This Holiday Season | KFF  Accessed November 17, 2023391312171727\n682436434749\n723433365953\n0 10 20 30 40 50 60 70 80 90 100Any of these precuationsTaking a COVID-19 test before visiting with friends or familyAvoiding dining indoors at restaurantsAvoiding travelWearing a mask in crowded placesAvoiding large gatherings\nPercentPercent who say they are taking each of the following precautions because of \nCOVID -19 this fall and winter: \nBlack Hispanic White\nAdults ages 65 years and older were more concerned about COVID- 19 disease and had \nhigher confidence in vaccine safety and vaccine importance than those <65 years.\n–Black adults were more concerned about COVID -19 disease than people of other racial and \nethnic groups.\n–Confidence in COVID -19 vaccine safety and importance varied by racial and ethnic group. \nHalf of adults reported plans to take precautions because of COVID- 19 during the fall \nand winter months, with 41% of adults ages ≥65 years planning to avoid large \ngatherings.\n–Larger proportions of Black and Hispanic adults report they plan to take precautions against \nCOVID -19 than White adults. Summary\nValues \n44\nValues\nCriteria 1:\nDo older adults feel that the desirable effects are large relative to undesirable \neffects?\n•How do older adults view the balance of desirable versus undesirable effects?\n•Would older adults feel that the benefits outweigh the harms?\noMinimal oSmall oModerate oLarge oVaries oDon’t know\nValues\nCriteria 2:\nIs there important uncertainty about, or variability in, how older adults value \nthe main outcomes?\n•Is there evidence that the variability is large enough to lead to different decisions?\noImportant uncertainty or variability\noProbably important uncertainty or variability\noProbably not important uncertainty or variability\noNo important uncertainty or variability\noNo known undesirable outcomesMajority opinion  \nMinority opinion  \nEtR Domain:\nAcceptability  \n\n4848Percent vaccinated with 2023 -24 COVID- 19 vaccine\nNational Immunization Survey -Adult COVID Module (NIS -ACM)\nCOVID -19 Vaccination Coverage with 2023- 24 Vaccine \nAmong Adults ≥18 Years, NIS- ACM\n0.010.020.030.040.050.0Vaccinated with 2023 -24 COVID -19 vaccine (%)\nWeek end dateAll adults 18+\n75+\n65-74\n50-64\n40-49\n30-39\n18-29\n4949Top COVID -19 vaccination concerns and issues among adults ≥65 years of \nage, by status/intent, Omnibus Surveys, January 5 – 29, 2024 (N=882)\nOther response options included: \"Too busy or kept forgetting,\" \"Cost/time concerns,\" \"Unsure if eligible,\" \"Fertility issues ,\" \"HCP recommended against,\" \"Other concern.\"\n*Option not offered to those who already received the vaccine.\nOmnibus Surveys: Data for this analysis were collected through the Ipsos KnowledgePanel  and NORC AmeriSpeak  Omnibus Surveys, which use probability -based panels to survey a nationally representative sample of U.S. adults aged 18 \nyears and older. CDC fields questions about vaccination status, intent, knowledge, attitudes, beliefs, and behaviors on each survey for 2 waves each month, for a combined sample size of ~4,000 respondents. These slides present results \nfrom January (N=4,287). Data were weighted to represent the non -institutionalized U.S. population and mitigate possible non- resp onse bias. All responses are self -reported. 6.1%\n5.5%\n5.0%\n2.8%\n2.7%\n2.6%\n1.3%\n1.2%\n0 25 50 75 100Effectiveness\nUnknown serious\nside effects\nMild side\neffects\nDo not trust\ngov. or pharma\nNot enough studies\n(human trials)\nHeart -related\nissues\nHard to get\nappointment\nImpact of side effects\non work/school\nWeighted % (95% confidence interval)Received/definitely wi ll get\n(N=450)\n83.8% reported \"No concerns or issues\"15.6%\n12.6%\n11.7%\n10.6%\n10.0%\n9.1%\n8.7%\n8.0%\n0 25 50 75 100Unknown serious\nside effects\nNo provider\nrecommendation\nEffectiveness\nNot enough studies\n(human trials)\nMild side\neffects\nPerceived natural\nimmunity*\nHad enough\nvaccines*\nHeart -related\nissues\nWeighted % (95% confidence interval)Probably will get/unsure\n(N=157)\n47.1% reported \"No concerns or issues\"53.2%\n49.6%\n48.6%\n41.9%\n37.7%\n17.5%\n13.2%\n10.2%\n0 25 50 75 100Unknown serious\nside effects\nDo not trust\ngov. or pharma\nNot enough studies\n(human trials)\nEffectiveness\nHeart -related\nissues\nHad enough\nvaccines*\nPerceived natural\nimmunity*\nMild side\neffects\nWeighted % (95% confidence interval)Probably/definitely will NOT get\n(N=275)\n9.6% reported \"No concerns or issues\"\n5050Key attitudes and experiences among adults 18 years and older, December 2023\nNational Immunization Survey -Adult COVID Module (NIS -ACM)\nThe December estimates are based on data collected November 26 through December 30.\nCDC. COVID -19 Vaccination Coverage and Vaccine Confidence Among Adults. https://www.cdc.gov/vaccines/imz -managers/coverage/covidvaxview/interactive/adults.html  \nAccessed February 7, 2024COVID -19 Vaccination Key Attitudes and Experiences by Vaccination Status \nAmong Adults Age ≥18 Years, NIS -ACM, December 2023\n19% of adults received a healthcare provider \nvaccine recommendation; highest among \nadults who were vaccinated or definitely plan \nto get vaccinated.1931\n26\n1415\n05101520253035\nHealthcare provider recommended I get a COVID-19 vaccinePercent\nOverall Vaccinated with 2023-24 COVID-19 vaccine\nDefinitely will get vaccinated Probably will get vaccinated or unsure\nProbably or definitely will not get vaccinated\n5151Key attitudes and experiences among adults 18 years and older, December 2023\nNational Immunization Survey -Adult COVID Module (NIS -ACM)\nThe December estimates are based on data collected November 26 through December 30.\nCDC. COVID -19 Vaccination Coverage and Vaccine Confidence Among Adults. https://www.cdc.gov/vaccines/imz -managers/coverage/covidvaxview/interactive/adults.html  \nAccessed February 7, 2024COVID -19 Vaccination Key Attitudes and Experiences by Age Group \nAmong Adults Age ≥18 Years, NIS -ACM, December 2023\nHealthcare provider recommendation was \nhighest among adults ages ≥65 years. 152227\n051015202530\nHealthcare provider recommended I get a COVID-19 vaccinePercent\n18 - 49 years 50 - 64 years 65+ years\n5252Intent to receive additional  COVID -19 vaccine dose among adults ≥18 years \nof age who received a dose since September 14, 2023, Omnibus Surveys, \nNovember 30, 2023 -January 16, 2024 (N=1,331)\n*Labels for estimates <4% not shown. †NORC and Ipsos base urbanicity on different, but comparable measures. NORC uses Census tract -based RUCA (Rural -Urban -Commuting A rea) codes, whereas Ipsos uses Office of Management and \nBudget's CBSA (Core Based Statistical Area) classification. §Includes plans purchased through employer, insurance companies, marketplaces, military insurance, Medicare, Medicaid, VA, IHS , and \"other.“\nOmnibus Surveys: Data for this analysis were collected through the Ipsos KnowledgePanel  and NORC AmeriSpeak  Omnibus Surveys, which use probability -based panels to survey a nationally representative sample of \nU.S. adults aged 18 years and older. CDC fields questions about vaccination status, intent, knowledge, attitudes, beliefs, an d behaviors on each survey for 2 waves each month, for a combined sample size of ~4,000 \nrespondents. These slides present results from January (N=4,287). Data were weighted to represent the non -institutionalized U.S.  population and mitigate possible non -response bias. All responses are self -reported. 62.9 5.6 31.5\n63.4\n62.44.3\n6.932.3\n30.7\n59.1\n59.9\n68.47.3\n5.0\n4.433.6\n35.1\n27.2\n63.7\n61.3\n64.1\n57.311.2\n14.832.9\n27.5\n21.1\n40.1\n0 25 50 75 100Overall (N=1,331)\nFemale (N=629)Male (N=702)\nAge 65+ (N=493)Age 50-64 (N=387)Age 18-49 (N=451)\nOther, non -Hispanic* (N=114)Hispanic (N=129)Black, non -Hispanic (N=90)White, non -Hispanic* (N=998)\nWeighted %66.3\n60.9\n60.86.6\n7.330.0\n32.5\n31.8\n57.0\n62.7\n65.3\n62.911.1\n6.4\n4.4\n5.331.9\n30.9\n30.3\n31.9\n58.8\n60.0\n65.1\n65.14.7\n6.5\n6.2\n4.936.5\n33.5\n28.7\n30.0\n63.1\n53.25.6\n9.831.2\n37.0\n0 25 50 75 100Rural (N=170)Suburban (N=654)Urban*†(N=507)\n$75,000+ (N=837)$50,000- $74,999 (N=227)$25,000- $49,999 (N=180)Income $24,999 or less (N=87)\nWest (N=387)South (N=383)Midwest (N=340)Northeast (N=221)\nUninsured (N=33)Insured§(N=1,250)\nWeighted %\n\nDomain Equity Question:\nIs the intervention equally acceptable across all \npopulations?\n\nAmong adults age ≥18 years responding to the NIS -ACM during Nov. 26 –  Dec. 30, 2023:\nVaccination coverage differed by race/ethnicity. \n–Coverage was highest among White, non-Hispanic adults and lowest among American \nIndian/Alaska Native and Native Hawaiian/Other Pacific Islander adults.\nVaccination coverage was higher in urban and suburban areas compared with rural \nareas.\nAdults with health insurance had significantly higher vaccination coverage than adults without insurance.\nVaccination coverage increased with increasing household income.Is the intervention equally acceptable across all populations?\nNIS-ACM: National Immunization Survey -Adult COVID Module 54\n5555Intent to receive additional  COVID -19 vaccine dose among adults ≥18 \nyears of age who received a dose since September 14, 2023, Omnibus \nSurveys, November 30, 2023 -January 16, 2024 (N=1,331)\n*Labels for estimates <4% not shown. †NORC and Ipsos base urbanicity on different, but comparable measures. NORC uses Census tract -based RUCA (Rural -Urban -Commuting A rea) codes, whereas Ipsos uses Office of Management and Budget's CBSA (Core Based \nStatistical Area) classification. §Includes plans purchased through employer, insurance companies, marketplaces, military insurance, Medicare, Medicaid, VA, IHS , and \"other.“\nOmnibus Surveys: Data for this analysis were collected through the Ipsos KnowledgePanel  and NORC AmeriSpeak  Omnibus Surveys, which use probability- based panels to survey a nationally representative sample of U.S. adults aged 18 years a nd \nolder. CDC fields questions about vaccination status, intent, knowledge, attitudes, beliefs, and behaviors on each survey for  2 waves each month, for a combined sample size of ~4,000 respondents. These slides present results from January \n(N=4,287). Data were weighted to represent the non -institutionalized U.S. population and mitigate possible non -response bias. Al l responses are self -reported. 62.9 5.6 31.5\n63.4\n62.44.3\n6.932.3\n30.7\n59.1\n59.9\n68.47.3\n5.0\n4.433.6\n35.1\n27.2\n63.7\n61.3\n64.1\n57.311.2\n14.832.9\n27.5\n21.1\n40.1\n0 25 50 75 100Overall (N=1,331)\nFemale (N=629)Male (N=702)\nAge 65+ (N=493)Age 50-64 (N=387)Age 18-49 (N=451)\nOther, non -Hispanic* (N=114)Hispanic (N=129)Black, non -Hispanic (N=90)White, non -Hispanic* (N=998)\nWeighted %66.3\n60.9\n60.86.6\n7.330.0\n32.5\n31.8\n57.0\n62.7\n65.3\n62.911.1\n6.4\n4.4\n5.331.9\n30.9\n30.3\n31.9\n58.8\n60.0\n65.1\n65.14.7\n6.5\n6.2\n4.936.5\n33.5\n28.7\n30.0\n63.1\n53.25.6\n9.831.2\n37.0\n0 25 50 75 100Rural (N=170)Suburban (N=654)Urban*†(N=507)\n$75,000+ (N=837)$50,000- $74,999 (N=227)$25,000- $49,999 (N=180)Income $24,999 or less (N=87)\nWest (N=387)South (N=383)Midwest (N=340)Northeast (N=221)\nUninsured (N=33)Insured§(N=1,250)\nWeighted %\n\nAs of February 2024, v accination coverage with 2023 -2024 COVID -19 vaccine was \nhighest among older adults ages 65 –  74 years and 75+ years, compared to younger age \ngroups.\n–Disparities in COVID -19 vaccine coverage are observed across many demographic factors, \nincluding race, ethnicity, insurance status and rurality.\nAdults  who were vaccinated or definitely plan to get vaccinated were more likely to \nreport that a healthcare provider recommended they get a COVID- 19 vaccine.\n–Adults ≥65 years were more likely to report a healthcare provider recommendation than \nyounger adults.\nAmong adults ≥65 years of age who had already received a 2023 -2024 Formula COVID -\n19 vaccine dose, 68.4% reported they definitely will get an additional dose of 2023 -\n2024 Formula COVID -19 vaccine if it is recommended for them.Summary\nAcceptability \n56\nAcceptability\nWould recommending an additional dose of 2023 -2024 Formula COVID -19 \nvaccine for older adults be acceptable to key stakeholders?\n•Are there key stakeholders that would not accept the distribution of benefits \nand harms?\n•Are there key stakeholders that would not accept the undesirable effects in the short term for the desirable effects (benefits) in the future?\noNooProbably no oProbably yes oYesoVaries oDon’t know\nMinority opinion  Majority opinion  \nEtR Domain:\nFeasibility \n\n59COVID -19 vaccines are now available on the commercial market.\n–COVID -19 vaccines are covered by private and public insurance and available through \nthe Bridge Access Program and Vaccines for Children for those that are uninsured or \nunderinsured.\nACIP recommendation would be needed for insurance coverage of an additional dose of 2023- 2024 Formula COVID -19 vaccine.\n–Insurance coverage generally required under either a “should” or “may” recommendation.Financial Barriers\n60Additional dose recommendation would be for same formula (2023 -2024) of COVID -19 \nvaccine that is currently available.\n–Existing COVID -19 vaccine administration infrastructure and product can be used.\n–Age-based recommendation would not be overly burdensome to implement.\nAdditional dose recommendation in those ≥65 years would add complexity to COVID-\n19 vaccine recommendations which have been getting simpler.\n–Frequent changes to vaccine recommendations can lead to vaccine fatigue.\n–Systems are already planning for next season, and adding more recommendations for this \nyear could add additional burden to an already fatigued system.\n–Minimum interval of 4 months used for additional dose recommendations may confuse providers accustomed to 2 month interval from the fall dose.\n–Providers would need to consider anticipated availability of updated vaccine next fall when considering providing vaccine doses during the summer months.Implementation and vaccine access\nDomain Equity Question:\nIs the intervention equally feasible to implement \nacross all populations?\n\nPast reports of sites being unaware of additional dose recommendations or requiring \ndocumentation to prove eligibility for additional vaccine dose. \n–Wide communication of any change in recommendations and that self -attestation is \nappropriate will be important to decrease barriers.\nThe Bridge Access Program was designed to remove patient barriers to COVID -19 \nvaccines, however disparities in vaccine uptake by insured status continue.\nTo the extent that existing disparities in vaccine uptake by characteristics such as race/ethnicity, urbanicity, and income are driven by differences in vaccine access, additional dose recommendations may further increase those disparities.\n–Access issues may be increased during a time when there are fewer off -site vaccination \nclinics, which are more common during fall vaccine roll -outs.\nIn the absence of an ACIP recommendation, additional doses might be an out- of-pocket \ncost, therefore those able to pay for an additional dose may have access while others do not.Implementation equity considerations\n62\nCOVID -19 vaccines currently on the commercial market and  an ACIP recommendation \n(should or may) would be needed for insurance coverage of an additional dose.\nAdditional dose recommendation would leverage existing infrastructure and vaccine \nproduct; however, it would add complexity to the current recommendations which could enhance vaccine and system fatigue.\nAccess related barriers to COVID -19 vaccines and disparities in vaccine uptake remain \nand additional dose recommendations may further heighten those inequities, but lack of recommendation limits access to those able to pay for vaccine out -of-pocket.Summary\nFeasibility \n63\nFeasibility\nIs an additional dose of the 2023-2024 Formula COVID -19 vaccine feasible to \nimplement among older adults?\n•Is the 2023- 2024 Formula COVID -19 vaccine program sustainable?\n•Are there barriers that are likely to limit the feasibility of implementing the 2023 -\n2024  Formula COVID -19 vaccine or require considerations when implementing it?\n•Is access to the 2023- 2024 Formula COVID -19 vaccine an important concern?\noNooProbably no oProbably yes oYesoVaries oDon’t know\nEtR Domain:\nResource Use \n\n66Scenario analysis: probability of hospitalization1, societal \nperspective  \nICER ($/QALY) \nAge \ngroupStrategy Base case ¼ base case ½ base case 2x base case 3x base case 4x base case\n65+ yUpdated Covid- 19 vax, 1 dose $11,936 $93,904 $52,541 Cost saving Cost saving Cost saving\nUpdated Covid- 19 vax, 2 doses $255,122 $624,028 $433,533 $120,341 $64,599 $34,133\nICER=Incremental cost effectiveness ratio; QALY=Quality -adjusted life year\n1 From Ko et al 2021. Adjusted risk of hospitalization by underlying condition: chronic obstructive pulmonary disease: 0.9, his tory of stroke: 0.9, coronary artery disease: 1.3, \nasthma: 1.4, hypertension: 2.8, obesity: 2.9, diabetes: 3.2, chronic kidney disease: 4.0, severe obesity: 4.4.\nDomain Equity Question:\nIs the intervention a reasonable and efficient \nallocation of resources across all populations?\n\nAn additional dose of COVID- 19 vaccine is most cost -effective in older adults in which \ndisease burden is highest compared to younger adults.\nAn additional dose of COVID- 19 vaccine is likely more cost -effective in populations with \na higher prevalence of risk factors, such as underlying conditions, which increase their \nprobability of hospitalization due to COVID- 19.Is the intervention a reasonable and efficient allocation of \nresources across all populations?\n68\nThe cost effectiveness of an additional dose in older adults is highly sensitive to COVID-\n19-associated hospitalization rates and anticipated rates in the coming months are \nuncertain.\n–COVID -19-associated hospitalization rates in older adults that are higher than those seen last \nyear would increase the cost effectiveness, however lower COVID -19 hospitalization rates \nwould decrease the cost effectiveness.\nEstimates that approximate cost- effectiveness for those with high- risk conditions such \nas underlying conditions or advanced age are more favorable.Resource Use\nSummary \n69\nResource Use\nIs an additional dose of the 2023-2024 Formula COVID -19 vaccine in older \nadults a reasonable and efficient allocation of resources?\n•What is the cost- effectiveness of the 2023 -2024 Formula COVID -19 vaccine?\n•How does the cost- effectiveness of the 2023 -2024 Formula COVID -19 vaccine change \nin response to changes in context, assumptions, etc.?\noNooProbably no oProbably yes oYesoVaries oDon’t know\nSummary and Work Group Interpretations  \n–Greatest benefit of a vaccine dose would be in those who have not yet received a \n2023- 2024 Formula dose, particularly older adults and those with underlying medical \nconditions. \n•Data presented today emphasized the importance of any dose of updated (2023 -\n2024 Formula) COVID -19 vaccine in older adults.\n–Risk of severe illness due to COVID- 19 continues throughout the year and is highest in \nthose ≥65 years.\n•Within the ≥65 -year age group, risk increases with increasing age.\n–Receipt of 2023- 2024 Formula COVID -19 vaccine provides protection against JN.1 and \nother circulating variants, however vaccine effectiveness is expected to wane.\n•In the past, we have seen greater durability in the protection against critical illness.Summary and Work Group Interpretations \n72\n–“May” recommendation would provide flexibility for older adults to obtain an \nadditional dose if they or their healthcare provider feel they would benefit.\n•Most benefit would likely be in those with underlying medical conditions, advanced age, or circumstances that may increase risk (e.g., nursing home resident).\n–Additional dose in adults ≥65 years may restore protection that has waned. \n•Smaller, incremental benefit on top of the protection still being provided by the initial 2023 -2024 Formula COVID -19 vaccine dose.\n–Cost effectiveness of an additional dose depends on COVID- 19 hospitalization rates in \nthe coming months and the patient risk factors for severe illness due to COVID- 19.\n–As COVID -19 epidemiology changes with time, additional dose recommendations \nmay not be needed in the future. Summary and Work Group Interpretations \n73\n7474Considerations for an additional dose recommendation\nPros Cons\n•“May” recommendation would provide \nflexibility for those ≥65 years to get an additional dose if they or their healthcare provider feel they would benefit.•Smaller, incremental benefit compared to that from initial 2023 -2024 COVID -19 \nvaccine dose in the fall. \n•Restore vaccine effectiveness that may have waned since the initial 2023 -2024 \nCOVID -19 vaccine dose.•May decrease vaccine confidence in the benefits of a single dose of 2023 -2024 \nCOVID -19 vaccine.\n•Acknowledges that risk of severe illness due to COVID -19 continues throughout \nthe year for older adults, despite upticks during winter months.•Additional recommendations may increase vaccine fatigue, potentially reducing uptake of vaccine next fall.\n75EtR Domain​​​ ​​Question​ Work Group Judgments\nPublic Health \nProblem​​​Is COVID -19 disease among persons ages 65 years and older of \npublic health importance?Yes\nBenefits and HarmsHow substantial are the desirable anticipated effects? Moderate\nHow substantial are the undesirable anticipated effects? Small\nDo the desirable effects outweigh the undesirable effects? Favors intervention\nValues​​​Do older adults feel that the desirable effects are large relative \nto undesirable effects?Large \nIs there important uncertainty about, or variability in, how older adults value the main outcomes?Probably important uncertainty \nor variability  \nAcceptability​​​Would recommending an additional dose of 2023 -2024 Formula \nCOVID -19 vaccine for older adults be acceptable to key \nstakeholders?Probably yes \nFeasibility​​​Is an additional dose of the 2023 -2024 Formula COVID -19 \nvaccine feasible to implement among older adults?​​​Probably yes\nResource Use​​​Is an additional dose of the 2023 -2024 Formula COVID -19 \nvaccine a reasonable and efficient allocation of resources?​​​Probably yes \n76Evidence to Recommendations Framework\nSummary: Work Group Interpretations \nBalance of \nconsequencesUndesirable \nconsequences \nclearly \noutweigh \ndesirable \nconsequences \nin most \nsettingsUndesirable \nconsequences \nprobably \noutweigh \ndesirable \nconsequences \nin most \nsettingsThe balance \nbetween \ndesirable and \nundesirable \nconsequences \nis closely \nbalanced or \nuncertainDesirable \nconsequences \nprobably \noutweigh \nundesirable \nconsequences \nin most \nsettingsDesirable \nconsequences \nclearly \noutweigh \nundesirable \nconsequences \nin most \nsettingsThere is \ninsufficient \nevidence to \ndetermine the \nbalance of \nconsequences\n77Evidence to Recommendations Framework\nSummary: Work Group Interpretations \nType of \nrecommendationWe do not recommend \nthe interventionWe recommend the \nintervention for individuals \nbased on shared clinical \ndecision -makingWe recommend the \nintervention \nACIP recommends that persons ≥65 years of age may receive an \nadditional dose of 2023 -2024 Formula COVID- 19 vaccineProposed ACIP Voting Language\n78\nPeople ages 65 years and older may receive 1 additional dose of any updated (2023 –2024 \nFormula) COVID -19 vaccine (i.e., Moderna, Novavax, Pfizer- BioNTech), informed by the \nclinical judgement of a healthcare provider and personal preference and circumstances. \nConsiderations for the additional dose may include a person’s risk for severe COVID- 19 \ndue to age and the presence of underlying medical conditions. The additional dose is administered at least 4 months following the previous dose of updated (2023 –2024 \nFormula) COVID -19 vaccine. Proposed Clinical Considerations\nNote: For initial vaccination with Novavax COVID -19 Vaccine, the 2 -dose series should be completed before administration of the additional dose. 79\nAcknowledgements  \n80Lakshmi Panagiotakopoulos\nMonica Godfrey\nDanielle Moulia\nKatherine Fleming -Dutra\nRuth Link -Gelles\nSarah Meyer\nElisha Hall\nJennifer Kriss\nKayla Calhoun\nKevin Chatham- Stephens\nSusan Goldstein\nMary Chamberland\nJoEllen Wolicki\nLauren Roper\nKaren Broder Evelyn Twentyman \nSierra Scarbrough\nNatalie Thornburg\nJefferson Jones\nAron Hall\nDave Wentworth\nCOVID -NET\nUniversity of Michigan COVID -19 Vaccination Modeling \nTeam\nImmunization Safety Office  \nImmunization Services Division\nCoronavirus and other Respiratory Viruses Division\nNational Center for Immunization and Respiratory \nDiseases \nFor more information, contact CDC\n1-800- CDC- INFO (232 -4636)\nTTY:  1 -888 -232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention.\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nThank you", "summary": "Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. Evidence to Recommendations Framework: Additional Dose of 2023-2024 Formula COVID -19 Vaccine in Older Adults  Megan Wallace, DrPH, MPH ACIP Meeting February 28, 2024…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-28-29-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-02-28-29/06-COVID-Wallace-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 81}
{"title": "07 COVID Panagiotakopoulos 508", "content": "Centers for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nNext Steps for the COVID- 19 Vaccine Program\nLakshmi Panagiotakopoulos, MD, MPH\nACIP MeetingFebruary 28, 2024\nCan we improve the current COVID- 19 \nvaccine policy timeline?\nmRNA updated (2023 –2024 Formula) vaccines were authorized or \napproved on September 11, 2023\nACIP met September 12, 2023 to review the available evidence for \nupdated COVID -19 vaccines (monovalent, XBB.1.5 component)\nACIP recommended updated COVID -19 vaccines as authorized under EUA \nor approved by BLA in persons aged ≥6 months:\n–Moderna COVID -19 vaccine in persons ≥6 months \n–Pfizer- BioNTech COVID -19 vaccine in persons ≥6 months \n–Novavax COVID- 19 vaccine in persons ≥ 12 years*COVID- 19 Vaccine Policy Decision – Fall 2023\n3ACIP: Advisory Committee on Immunization Practices  |  EUA: Emergency Use Authorization  |  BLA: Biologics License Application \n*Novavax authorized for use on October 3, 2023\nTimeline:  Fall 2023 COVID -19 Vaccine Recommendation\nSeptember 12\nACIP Vote and CDC \nRecommendation \nfor the Updated \n2023 -2024 COVID -\n19 Vaccine \nSeptember 15\nUpdated \nInterim Clinical \nConsiderations \non the Use of \nCOVID -19 \nVaccines PostedSeptember 19 \nCOCA Call on \nRecommendations \nfor Influenza, \nCOVID -19, and RSV \nVaccines for Older \nAdults \nSeptember 27\nImmunization \nscheduled \nupdatedOctober 3\nNovavax \nUpdated 2023-\n2024 COVID -\n19 vaccine \nauthorized\nOctober 10\nMMWR on Use \nof Updated \n2023 –2024 \nCOVID -19 \nVaccines\nACIP: Advisory Committee on Immunization Practices  |  CDC: Centers for Disease Control and Prevention |  COCA: Clinician Outreach and Communication Activity |  \nMMWR: Morbidity and Mortality Weekly Report  \nhttps://www.cdc.gov/vaccines/covid -19/clinical- considerations/covid -19-vaccines -us.html  |  https://www.cdc.gov/mmwr/volumes/72/wr/mm7242e1.htm  4\nCOVID -19 related hospitalizations had already begun to increase before \nthe ACIP vote on use of the updated (2023 -2024) COVID -19 vaccine\nWeekly COVID -19 new hospital admissions – National Healthcare Safety Network (NHSN), United States, June 2023 – January 2024 \nhttps://covid.cdc.gov/covid -data -tracker/#trends_weeklyhospitaladmissions_select_00    \nACIP Vote and CDC \nRecommendation\n5\nUncertainty around recommendations made planning for state and local vaccine \nprograms challenging\nVaccine orders had to be placed prior to knowing groups for whom vaccine would be recommended\nStakeholder presentations, provider toolkits, and webpages all had to be updated after recommendation was made, limiting available window for communication of recommendation prior to the respiratory virus season\nThere were reports of issues with vaccine access, including among those at highest risk of severe illnessWhat happened after  the Fall updated (2023 -2024) COVID -\n19 vaccine policy vote?\n6\nLess lead time for planning (e.g., staffing, scheduling, EHR prompts)\nA new recommendation may occur during a surge in COVID -19 associated \nhospitalizations and may not provide enough time for distribution, partner \nengagement, preparation of healthcare providers and facilities, and uptake to mitigate the rise in disease\nMay limit ability to coordinate messaging surrounding the fall/winter respiratory virus season and promote importance of COVID -19 vaccination in communications \nLikely limit ability to plan vaccination clinics with COVID -19, flu, and/or RSV vaccine in \nsettings such as long -term care facilities, communities, workplaces, and schools \nEHR: Electronic health recordPotential impacts of continuing with a Fall vote for the \n2024 -2025 COVID -19 vaccine\n7\n8Annual seasonal influenza vaccine timeline\nFeb March April July May June Aug Sep Oct Nov Dec\nWHO Vaccine \nComposition \nRecommendationsFDA VRBPAC \nMeetingACIP votes on \nproposed \nrecommendations \nFDA issues sBLAsJan\nManufacturers distribute vaccine\nProviders administer vaccine\nWHO : World Health Organization | FDA: Food and Drug Administration | VRBPAC : Vaccines and Related Biologic Products Advisory Committee | ACIP : Advisory Committee on \nImmunization Practices | CDC: Centers for Disease Control and Prevention | sBLAs : Supplemental Biologics License Applications CDC/ACIP \nrecommendations \npublished \nCurrent Time Frame for Updated COVID -19 Vaccine Availability\nDec. Jan. Feb. Mar. Apr. May Jun. Jul. Aug. Sep. Oct. Nov. Dec.Year -round genetic and phenotypic characterization\nWHO TAG -CO-VAC\nRecommendation •Timing of TAG- CO-VAC recommendations and regulatory review for 2022 and 2023 shown\nVaccine manufacturing etc.\nVaccine distribution & administrationIdentify vaccine \ncandidates\nProduce \nantisera to \ncandidatesAnalyze neutralization of  \nrecent virusesFDA \nVRBPAC FDA license approval\nCurrent timing for the vaccine strain composition is challenging for the manufacture and \ndistribution of vaccine early in the Fall \nSlide for discussion purposes. Information is approximated and exact timelines for manufacturing are inferred. \nWHO : World Health Organization | TAG -CO- VAC: Technical Advisory Group on Covid -19 Vaccine Composition  |  FDA : Food and Drug Administration | VRBPAC : Vaccines and \nRelated Biologic Products Advisory Committee | ACIP : Advisory Committee on Immunization PracticesACIP Rec.\n9\nDec. Jan. Feb. Mar. Apr. May Jun. Jul. Aug. Sep. Oct. Nov. Dec.ACIP Rec. Revised Time Frame for 2024 -2025 COVID -19 Vaccine Availability\nYear -round genetic and phenotypic characterization\nVaccine manufacturing etc.\nVaccine distribution & administrationIdentify vaccine \ncandidates\nProduce \nantisera to \ncandidatesAnalyze neutralization of  \nrecent viruses\nFDA \nVRBPACFDA license approval\nProposed changes: WHO -TAG-CO-VAC mid -late April (exact date to be determined), FDA VRBPAC in May, ACIP in JuneWHO TAG -CO-VAC\nRecommendation? \nSlide for discussion purposes. Information is approximated and exact timelines for manufacturing are inferred. \nWHO : World Health Organization | TAG -CO- VAC: Technical Advisory Group on Covid -19 Vaccine Composition  | FDA : Food and Drug Administration | VRBPAC : Vaccines and \nRelated Biologic Products Advisory Committee | ACIP : Advisory Committee on Immunization Practices\nVaccines and Related Biological Products Advisory Committee May 16, 2024 Meeting Announcement - 05/16/2024 | FDA10\nACIP meeting in June to review evidence for 2024 -2025 COVID -19 vaccine \nrecommendations, including:\n–WHO and FDA antigen selections\n–Manufacturer studies and immunogenicity data \n–Cumulative effectiveness and safety data\n–Epidemiology from current and prior years\n–Uptake from current and prior years\n–Cost effectiveness\nACIP vote on 2024 -2025 COVID -19 vaccine recommendations in June\n2024 -2025 Formula will become available as regulatory actions are taken \nby FDA and vaccines are distributed by manufacturersProposed COVID- 19 Vaccine Policy plan - 2024\nACIP : Advisory Committee on Immunization Practices  |  WHO : World Health Organization  |  FDA : Food and Drug Administration 11\nPros and Cons of a June COVID -19 \nvaccine policy decision\nEnables early planning across entirety of healthcare delivery system\n•National, state and local public health departments\n•Large and small practices, other venues for vaccine delivery (e.g., pharmacies)\nAllows time for clear communication of recommendations\nProvides vaccine sites with earlier information on which to base ordering decisions\nVaccines potentially available immediately following FDA authorization or approval\nAlignment with influenza vaccine recommendations\nDecrease number of emergency ACIP meetingsPros of a June COVID- 19 vaccine policy decision\n13FDA : Food and Drug Administration  | ACIP : Advisory Committee on Immunization Practices  \n–Epidemiology and strain changes\n•Minor changes: unlikely to impact recommendation \n•Major changes: may require subsequent emergency action\n–Updated vaccine antigen changes do not require new human data \n•Manufacturers provide pre- clinical immunogenicity for VRBPAC antigen selection\n•Additional clinical trial data beyond that presented at VRBPAC may not be \navailable before ACIP votes (both for June and September)\n•Reliance on large body of cumulative effectiveness and safety data\n–Consistent temporal patterns of COVID -19 not yet established\n•While this is true, we have four years worth of epidemiologic data to predict a peak in the winter 2024- 2025Potential cons of a June COVID -19 policy decision\nVRBPAC : Vaccines and Related Biologic Products Advisory Committee  |  ACIP : Advisory Committee on Immunization Practices  14\nWe have more than four years worth of data on COVID -19 and three years worth of \ndata on COVID -19 vaccines\nWe have a well- established precedent from influenza vaccine recommendations\n–Virus evolves rapidly and updates to vaccine antigens are needed\nIt is unlikely there will be more data between June and September to influence \nupdated COVID- 19 vaccine policy decision\nIncreased lead time will ease implementation challenges for vaccine providers\nIncreased lead time can also allow for clearer messaging in provider and patient educational materialsTakeaways\n15\nImportant to separate policy question/decision from timing of decision\nWork group members were in favor of moving decision to June, and \ndiscussed many ways that this could ease implementation challenges, \nincluding clearer communication of vaccine policy and increase lead \ntime for clinicians\nWork group members emphasized that communication surrounding a \nrecommendation prior to updated vaccine availability, as done routinely \nfor influenza vaccine, will be importantWork Group Interpretation \n16\nMegan Wallace\nMary Chamberland\nKevin Chatham -Stephens\nMatthew Daley\nKatherine Fleming -Dutra\nMonica Godfrey\nSusan Goldstein\nLisa Grohskopf\nAron Hall\nElisha Hall\nSarah MeyerDanielle Moulia\nEvelyn Twentyman\nDavid Wentworth\nJoEllen Wolicki\nACIP COVID -19 Work Group\nImmunization Services Division\nImmunization Safety Office\nCoronavirus and Other Respiratory \nViruses Division\nNational Center for Immunization and Respiratory Diseases Acknowledgements \n17\nFor more information, contact CDC\n1-800- CDC- INFO (232 -4636)\nTTY:  1 -888 -232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention.\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.", "summary": "Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. Next Steps for the COVID- 19 Vaccine Program Lakshmi Panagiotakopoulos, MD, MPH ACIP MeetingFebruary 28, 2024 Can we improve the current COVID- 19  vaccine policy…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-28-29-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-02-28-29/07-COVID-Panagiotakopoulos-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 18}
{"title": "01 Chikungunya chen 508", "content": "CHIKUNGUNYA VACCINES\nWilbur Chen, MD, MS\nChair, ACIP Chikungunya Vaccines Work GroupACIP Meeting\nFebruary 28, 2024\nBackground\nChikungunya vaccine (manufactured by Valneva) was licensed in the \nUnited States in November 2023\nNo other chikungunya vaccine licensed globally\nNo existing ACIP chikungunya vaccine recommendations\nChikungunya Vaccines Work Group is developing policy options for ACIP’s consideration for use of chikungunya vaccine among U.S. persons at risk of \nchikungunya, including travelers, laboratory workers, and residents of U.S. \nterritories and states with risk of transmission\nRecap of previous Work Group presentations to ACIP (1) \nOctober 2022\n–Overview of chikungunya virus disease and vaccines\n–Immunogenicity and safety of Valneva’s chikungunya vaccine\nFebruary 2023\n–Global epidemiology of chikungunya\n–Chikungunya among U.S. travelers\n–Persistent arthralgia following chikungunya\nJune 2023\n–Value of a vaccine to U.S. travelers\n–Chikungunya virus infection among laboratory workers\n–Observations on a large chikungunya outbreak in Paraguay\nRecap of previous Work Group presentations to ACIP (2) \nOctober 2023\n–Evidence to Recommendations ( EtR) and proposed policy options for \nchikungunya vaccine use among U.S. adult travelers\n–EtR and proposed policy options for chikungunya vaccine use among \nU.S. laboratory workers\nOverview of today’s session\nUpdate on chikungunya vaccine licensure\nReview of proposed policy options for chikungunya vaccine use among \nU.S. adult travelers *\nReview of proposed policy options for chikungunya vaccine use among \nU.S. laboratory workers *\nProposed clinical guidance for vaccine use among pregnant and \nbreastfeeding persons\n*For vote today\nACIP Ex Officio ( cont ) Invited Consultants ( cont )\nWilbur Chen, Univ Maryland Lesley Dupuy, NIH Beth Bell, Univ Washington\nMatthew Daley, Kaiser Permanente Carina Blackmore, Florida Dept Health\nACIP Liaisons Alan Lam, DoD\nCDC Leads Elizabeth Barnett, ISTM Margaret Ryan, DoD\nSusan Hills, DVBD (Lead) James Campbell, AAP Steven Schofield, CATMAT\nNicole Lindsey, DVBD (Deputy Lead) Mary Pat Friedlander, AAFP David Shlim, Jackson Hole Travel & Trop Med\nSaroj Rai, AIM Nestor Sosa, Uni New Mexico Hospital\nEx Officio Sanet Torres, San Jorge Children & Women's Hospital\nRobin Levis, FDA Invited Consultants Kirsten Vannice, Bill & Melinda Gates Foundation\nSixun Yang, FDA Alan Barrett, Univ Texas Galveston Mary Wilson, Univ California San FranciscoChikungunya Vaccines Work Group members\nDVBD DGMQ ISD\nErin Staples Kevin McLaughlin Elisabeth Velazque z\nSarah Guagliardo\nAnn Powers DHQP GRADE/ETR consultants\nLaura Adams Michael McNeil Doug Campos -Outcalt\nJoshua Wong Rebecca Morgan\nGID\nNCEZID Rebecca Casey ACIP Secretariat\nRita Helfand Jessica MacNeil, NCIRD\nLeslie Lee, NCIRDChikungunya Vaccines Work Group CDC participants", "summary": "CHIKUNGUNYA VACCINES Wilbur Chen, MD, MS Chair, ACIP Chikungunya Vaccines Work GroupACIP Meeting February 28, 2024 Background Chikungunya vaccine (manufactured by Valneva) was licensed in the  United States in November 2023 No other chikungunya vaccine licensed globally No existing ACIP chikungunya vaccine recommendations Chikungunya Vaccines Work Group is developing policy options for ACIP’s consideration for use of chikungunya vaccine among U.S. persons at risk of  chikungunya, including…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-28-29-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-02-28-29/01-Chikungunya-chen-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 7}
{"title": "02 Chikungunya hills 508", "content": "National Center for Emerging and Zoonotic Infectious Diseases\nUPDATE ON LICENSURE OF LIVE \nATTENUATED CHIKUNGUNYA VACCINE\nSusan Hills, MBBS, MTH\nCDC Lead , Chikungunya Vaccines Work Group\nArboviral Diseases Branch\nDivision of Vector -Borne Diseases\nFort Collins, Colorado\n   ACIP meeting, February 28, 2024\nKey points from FDA licensure and package insert\nVaccine approved on November 9, 2023 and named IXCHIQ\nIndicated for individuals at increased risk of exposure to chikungunya virus  \nSingle dose primary schedule and for use in individuals aged ≥18 years\n\nContraindications\nImmunocompromised individuals\nIndividuals with a history of a severe allergic reaction (e.g., \nanaphylaxis) to any component of IXCHIQ\n2\nWarnings and precautions in package insert\nVaccine may cause severe or prolonged chikungunya -like adverse \nreactions\nVaccine viremia occurs in the first week following vaccination and \nno data on risk of vertical transmission to fetus or neonate \nLicensure through accelerated approval pathway\nTradition approval would have been challenging and clinical development \nwould likely have been delayed\n–Chikungunya outbreaks unpredictable and duration can be relatively short\n–No established immunologic correlate of protection\nAccelerated approval pathway endorsed at FDA VRBAC* meeting, 2019\n–FDA can grant for products for serious conditions that fill unmet medical need \n–Effectiveness demonstrated by controlled clinical trials showing vaccine has effect \non surrogate endpoint reasonably likely to predict clinical benefit\n–Marker of protection for chikungunya vaccine based on neutralizing antibody titer estimated from validated non -human primate model\n–Post-licensure requirement for controlled trials to confirm the clinical benefit \n*Vaccines and Related Biological Products Advisory Committee \nRequired post -marketing studies\nVaccine effectiveness case -control study in persons aged ≥12 years, \nBrazil\n–Plan to initiate by March 2026, complete by March 2028\nPragmatic randomized controlled trial for effectiveness and safety in \nadults in endemic area\n–Plan to initiate by Oct 2025, complete by Jul 2029", "summary": "National Center for Emerging and Zoonotic Infectious Diseases UPDATE ON LICENSURE OF LIVE  ATTENUATED CHIKUNGUNYA VACCINE Susan Hills, MBBS, MTH CDC Lead , Chikungunya Vaccines Work Group Arboviral Diseases Branch Division of Vector -Borne Diseases Fort Collins, Colorado    ACIP meeting, February 28, 2024 Key points from FDA licensure and package insert Vaccine approved on November 9, 2023 and named IXCHIQ Indicated for individuals at increased risk of exposure to chikungunya virus   Single…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-28-29-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-02-28-29/02-Chikungunya-hills-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 6}
{"title": "03 Chikungunya hills 508", "content": "National Center for Emerging and Zoonotic Infectious Diseases\nPROPOSED POLICY OPTIONS FOR \nCHIKUNGUNYA VACCINE USE AMONG \nU.S. ADULT TRAVELERS\nSusan Hills, MBBS, MTH\nCDC Lead , Chikungunya Vaccines Work Group\nArboviral Diseases Branch\nDivision of Vector -Borne Diseases\nFort Collins, Colorado\n   ACIP meeting, February 28, 2024\nChikungunya virus and transmission\nAlphavirus \nKey vectors are Aedes aegypti \nand Aedes albopictus mosquitoes\nMainly feed in daytime with peak \nactivity early morning and late \nafternoon\n\nOther uncommon transmission modes\nIntrauterine Intrapartum\nBloodborne Laboratory \nexposure\n\nDistribution and disease burden in endemic areas\nTypically tropical and \nsubtropical regions\nPeriodically causes large outbreaks \n–Often high attack rates\nVirus transmission usually \nhighest during wet season\nLarge numbers of cases reported annuallyCountries and territories with current or past transmission \nof chikungunya virus\n\nClinical features of acute chikungunya virus infection\nFebrile illness with typically severe \narthralgia, can be debilitating\nJoint symptoms involve multiple joints, most commonly hands and \nfeet\nOther symptoms include \nheadache, rash, myalgia, anorexia \nNo anti -viral treatment available\nImage above from : https://www.paho.org/en/topics/chikungunya\nComplications of chikungunya\nRare serious complications (e.g., \nmyocarditis, hepatitis, acute renal disease, \nneurologic illness)\nDeaths rare and reported mostly in\n–Older adults, particularly those with \ncomorbidities\n–Young infants infected perinatally or by mosquito bites\nImages from : https://www.paho.org/en/topics/chikungunya\nChronic arthralgia following chikungunya\nAcute symptoms usually resolve in 7 –10 days\nSome patients have continuation or relapse of symptoms\nStudies reported variable proportions of \npatients with persistent symptoms and likely \nvaries with\n–Severity of acute illness\n–Age\n–Preexisting joint problems\nOngoing arthralgia of variable severity possibly \npresent in up to ~50% at 3 months and up to \n~30% at 12 months\nChikungunya among U.S. travelers\nApproximately 100 –200 reported cases \nannually\nInfection most commonly acquired in \nlocations in Asia and Americas\nGreatest risk factor for travelers is traveling to area with outbreak\nExample of higher risk during outbreak: Risk for travelers \nto Paraguay in 2023\n<1%\nPercentage of all U.S. persons \ntraveling to areas with \nchikungunya risk visiting Paraguay 25%*\nPercentage of all reported U.S. traveler \nchikungunya cases who indicated they \nhad traveled to Paraguay\n*20 of 80 travelers with destination data, preliminary ArboNET  data, 2023\nChikungunya vaccine\nLive attenuated vaccine \nSingle dose schedule \nAdministered intramuscularly\nLicensure based on data from\n–~620 subjects for immunogenicity\n–~3,500 subjects for safety (including ~3,100 in pivotal clinical trial)\nShort - and long -term protection ( seroresponse  rates)\nShort -term protection (28 days after vaccination) \n–98% (611 of 622) combined seroresponse  rate from two studies\nLong-term protection (12 months after vaccination)\n–99% (356 of 360) seroreponse rate from one study \nWork Group summary\n–Although data are limited, vaccine highly immunogenic\nVaccine safety (1)\nPivotal Phase 3 clinical trial included 3,082 adults in vaccine arm and \n1,033 in placebo arm\nSolicited local reactions  within 10 days after vaccination\n–15% in vaccinees vs 11% in placebo recipients\nSolicited systemic adverse events  (AE) within 10 days after vaccination\n–50% in vaccinees vs 27% in placebo recipients\n–Most common were headache, fatigue and myalgia in ~25% –30% of vaccinees\nAny related severe sy stemic AEs *\n–1.9% in vaccinees vs 0.1% in placebo recipients\n–Commonest were fever (1.3%), arthralgia (0.3%), myalgia (0.3%) \n*Prevented daily activity or required medical attention or fever ≥39°C (102.1° F)\nVaccine safety (2)\nSerious adverse events  within 6 months of vaccination\n–1.5% in vaccinees vs 0.8% of placebo recipients \n–Two events in vaccinated subjects considered vaccine -related\nArthr algia/arthritis\n–Any arthralgia within 10 days in 17% vaccinees vs 5% placebo recipients\n–Severe arthralgia, persistent arthralgia, arthritis, and new onset or worsening \nosteoarthritis not reported in significantly higher percentage of vaccinees vs placebo recipients\nChikungunya- like adverse reactions: Background\nSafety outcome of interest has been chikungunya -like illness after vaccination\nWork Group had reviewed data on “adverse events of special interest” defined \nby manufacturer\nFDA-requested reanalysis based on revised case definition that was less \nrestrictive in terms of timing of onset of events, clustering of symptoms, and \nduration of events\n–Revised FDA definition was fever* and ≥1 of arthralgia or arthritis, myalgia, \nheadache, back pain, rash, lymphadenopathy, or certain neurological, cardiac or \nocular symptoms that occurred within 30 days after vaccination\n* Fever ≥100.4 °F\nChikungunya- like adverse reactions: Results per reanalysis\nChikungunya -like adverse reactions \n–11.7% (361 of 3,082) vaccine recipients and 0.6% (6 of 1,033) placebo \nrecipients \n–Most symptoms mild or moderate\nSevere reactions that prevented daily activity or required medical \nintervention, or fever ≥102.1 °F (39° C)\n–1.6% (n=48) vaccine recipients vs 0% of placebo recipients\nProlonged reactions with duration ≥30 days\n–0.5% (n=14) vaccine recipients vs 0% of placebo recipients\nChikungunya- like adverse reactions:\nWork Groups conclusions\nAlready considered reactogenic nature of vaccine\nLooked closely at similar events when conducting GRADE analysis\nNoted some other reactogenic vaccines have similar rates of adverse events\nIn Evidence to Recommendations framework when considering if desirable \neffects outweighed undesirable effects of vaccination had noted risk -benefit \nassessment\n–Will vary substantially depending on chikungunya virus transmission intensity \nand other factors\n–Was likely favorable if used in line with our proposed recommendations  \nNo change in Work Group assessment\nVaccine safety: Work Group summary\nReactogenic vaccine \nWill be important to continue to monitor vaccine safety post -\nlicensure\nSummary of Work Group considerations\nDisease that can result in severe arthralgia during the acute illness, \nrare serious complications, and sometimes long -term arthralgia\nHighest risk for severe outcomes is among older adults, particularly those with comorbidities, and neonates and young infants\nModerate disease burden among US travelers with 100- 200 cases \nreported annually\nSubstantially higher risk for infection if travel during an outbreak\nImmunogenic but reactogenic vaccine\nDraft recommendations for \nACIP’s consideration\nDraft recommendations\nChikungunya vaccine is recommended  for persons aged ≥18 years \ntraveling to a country or territory where there is a chikungunya \noutbreak\nIn addition, chikungunya vaccine may be considered  for the following \npersons traveling to a country or territory without an outbreak but with evidence of chikungunya virus transmission among humans within \nthe last 5 years\n–Persons aged >65 years, particularly those with underlying medical \nconditions, who are likely to have at least moderate exposure* to \nmosquitoes, OR\n–Persons staying for a cumulative period of 6 months or more\nProviding clarity on chikungunya outbreaks\nFor the purposes of the recommendation, an outbreak \nwill be defined as occurring when CDC posts information on an outbreak on CDC website \nShared clinical decision- making recommendation for \npersons aged >65 years or traveling for a longer duration\nMore uncertainty in risk -benefit assessment in these cases\nLikely to be circumstances where some individuals might reasonably \nchoose vaccination or some providers might wish to recommend it\nAppropriate to hold conversation between healthcare provider and patient about the risks and benefits including\n–likelihood of exposure based on factors including activities, time of year, \nduration of travel\n–disease and potential severity\n–vaccine efficacy\n–possibility of vaccine -associated adverse events\nTakes into account traveler’s personal perceptions and tolerance of risk\nPersons >65 years, particularly those with underlying \nmedical conditions\nKey risk factors for severe disease include older age and underlying \nmedical conditions (e.g., diabetes, cardiac disease, hypertension) \nKey risk factors for chronic arthralgia are older age and pre -existing joint \nproblems\n1. To ra le s  M, e t al.  MMWR Morb  Mortal Wkly  R ep 2023\nVaccine not \navailable for \nchildren Risk for higher morbidity and \nmortality in older persons \nsupported by data from recent \noutbreak in Paraguay1\nTravel for cumulative period of ≥6 months\nKey risk factor for chikungunya virus infection is intensity of \ntransmission \n–If equivalent transmission, cumulative duration of exposure important\nTransmission patterns can be unpredictable over longer term and likely  some seasonal variation in mosquito activity impacting risk\nExpatriates in location with risk might not have access to vaccine if risk increased or outbreak began\nProviding clarity on evidence of chikungunya virus \ntransmission among humans within the last 5 years\nRationale: 5 -year time frame provides interval that allows reasonable \nconfidence there is transmission or insufficient transmission to be concern \nfor travelers \nTool: Map that shows countries \nwith chikungunya virus \ntransmission among humans \nreported during last 5 years, \nposted on CDC website \nMock -up map to demonstrate transmission of chikungunya virus \namong humans during last 5 years\n\nProviding clarity on moderate exposure\nTravelers who might have at least 2 weeks (cumulative) of exposure to \nmosquitoes in indoor and/or outdoor settings\nDoes not include travelers who might have limited exposure to \nmosquitoes (e.g., those traveling for business and likely to be mainly in \nmosquito -protected indoor settings)\n65\nWork Group deliberations when developing \nrecommendations\nAim to balance desirable and undesirable effects of vaccination\n–“Recommended”: for travelers with highest risk\n–“May be considered”: some individuals might reasonably choose \nvaccination and some providers might wish to recommend it\nDraft recommendations\nChikungunya vaccine is recommended  for persons aged ≥18 years \ntraveling to a country or territory where there is a chikungunya \noutbreak\nIn addition, chikungunya vaccine may be considered  for the following \npersons traveling to a country or territory without an outbreak but with evidence of chikungunya virus transmission among humans within \nthe last 5 years\n–Persons aged >65 years, particularly those with underlying medical \nconditions, who are likely to have at least moderate exposure* to mosquitoes, OR\n–Persons staying for a cumulative period of 6 months or more\n*Moderate exposure could include travelers who might have at least 2 weeks (cumulative) of exposure to mosquitoes \nin indoor and/or outdoor settings", "summary": "National Center for Emerging and Zoonotic Infectious Diseases PROPOSED POLICY OPTIONS FOR  CHIKUNGUNYA VACCINE USE AMONG  U.S. ADULT TRAVELERS Susan Hills, MBBS, MTH CDC Lead , Chikungunya Vaccines Work Group Arboviral Diseases Branch Division of Vector -Borne Diseases Fort Collins, Colorado    ACIP meeting, February 28, 2024 Chikungunya virus and transmission Alphavirus  Key vectors are Aedes aegypti  and Aedes albopictus mosquitoes Mainly feed in daytime with peak  activity early morning…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-28-29-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-02-28-29/03-Chikungunya-hills-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 28}
{"title": "04 Chikungunya hills 508", "content": "National Center for Emerging and Zoonotic Infectious Diseases\nPROPOSED POLICY OPTIONS FOR \nCHIKUNGUNYA VACCINE USE AMONG \nU.S. LABORATORY WORKERS\nSusan Hills, MBBS, MTH\nCDC Lead , Chikungunya Vaccines Work Group\nArboviral Diseases Branch\nDivision of Vector -Borne Diseases\nFort Collins, Colorado\n   ACIP meeting, February 28, 2024\nChikungunya virus infections among laboratory workers\nAt least 44 infections identified among laboratory workers worldwide over \n~ 50 years1–3 \n–43 cases overt disease, 1 asymptomatic infection, no deaths\n4 disease cases in U.S. laboratorians since chikungunya became notifiable disease in 2015\n–Similar symptoms as with infection acquired via mosquito -borne route\n–One case hospitalized for observation, no deaths \nIdentified cases underestimate all infections as no formal laboratory surveillance system\n1.The Subcommittee on Arbovirus Laboratory Safety of the American Committee on Arthropod -Borne Viruses. Am J Trop Med Hyg 1980;\n2.Rusnak JM, et al. J Occup Environ Med 2004; 3. US national arboviral disease surveillance system, 2015 –2022 \nRoutes of laboratory transmission\nAerosol \nPercutaneous\n–Needlestick while working with and \ninjecting mice\n–Forceps prick while dissecting mosquitoes infected with chikungunya virus\nMucosal (possible)\n\nFactors for consideration\nVaccination required for only limited number of staff who might be \nexposed to live chikungunya virus\n–Vaccination not necessary for workers handling routine clinical samples \n–Recommendations only for laboratorians undertaking research or very \nspecific diagnostic work using live virus (e.g., plaque reduction \nneutralization tests)\nWork group summary\n–Benefits of vaccination outweigh risks for small group of laboratorians \nworking with live virus, given potential for acquiring chikungunya virus \ninfection which can result in severe polyarthralgia and possibly chronic \narthralgia \nDraft recommendation \nChikungunya vaccination is recommended for laboratory \nworkers with potential for exposure to chikungunya virus.\nInformation accompanying recommendations\nLocal biosafety committee should undertake risk assessment \nof potential for chikungunya virus exposure considering \n–Type of work to be performed \n–Biosafety level at which work is being conducted\nVaccination not necessary for workers handling routine clinical samples \nDraft recommendation \nChikungunya vaccination is recommended for laboratory \nworkers with potential for exposure to chikungunya virus.", "summary": "National Center for Emerging and Zoonotic Infectious Diseases PROPOSED POLICY OPTIONS FOR  CHIKUNGUNYA VACCINE USE AMONG  U.S. LABORATORY WORKERS Susan Hills, MBBS, MTH CDC Lead , Chikungunya Vaccines Work Group Arboviral Diseases Branch Division of Vector -Borne Diseases Fort Collins, Colorado    ACIP meeting, February 28, 2024 Chikungunya virus infections among laboratory workers At least 44 infections identified among laboratory workers worldwide over  ~ 50 years1–3  –43 cases overt…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-28-29-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-02-28-29/04-Chikungunya-hills-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 7}
{"title": "05 Chikungunya hills 508", "content": "National Center for Emerging and Zoonotic Infectious Diseases\nCLINICAL GUIDANCE FOR USE OF LIVE ATTENUATED \nCHIKUNGUNYA VACCINE AMONG PREGNANT AND \nBREASTFEEDING INDIVIDUALS\nSusan Hills, MBBS, MTH\nCDC Lead , Chikungunya Vaccines Work Group\nArboviral Diseases Branch\nDivision of Vector -Borne Diseases\nFort Collins, Colorado\n   ACIP meeting, February 28, 2024\nClinical guidance for use of live attenuated \nchikungunya vaccine in pregnant individuals\nPresentation of chikungunya among pregnant persons\nClinical disease similar to  non-pregnant persons\nOutcomes of chikungunya virus infection during pregnancy \nAdverse outcomes such as fetal loss, stillbirth, or preterm birth \ndocumented but rare\n–Mouse studies and examination of placentas from infected women suggest \nplacenta is refractory to chikungunya virus infection1,2 \nInfection commonly  results in adverse neonatal outcomes if pregnant \nindividual infected around time of delivery\n–In these cases, intrapartum transmission occurs in ~30% –50% cases3–6 \n–Mechanism considered to be transplacental transmission with hypothesis that maternal blood enters fetal circulation by placental barrier breaches \nfrom uterine contractions during labor  \n1. Fritel   X et al, Emerg  Infect Dis 2010; 2. Couderc T et al, PLoS Pathog 2008; 3. Gerardin P et al, PLoS Medicine 2008; 4. Ramful D et al, Ped Infect Dis J 2007; 5. \nTorres JR et al, Int J Infect Dis 2016; 6. Senanayake MP et al, Ceylon Med J 2009.\nDisease in neonates infected via intrapartum transmission\nSevere and sometime fatal illness\n–In one prospective study 53% (10 of 19 neonates) had severe disease1 \nPresentations include encephalopathy, sepsis -like illness, cardiac, \ndermatologic, and hemorrhagic manifestations\nNeurocognitive outcomes often poor, particularly if initial clinical \npresentation with encephalopathy\nBin S et al, Clin Case Rep 2023\n Jebain  J et al, ID Cases 2020\n Villamil -Gomez W et al, J Trop Ped 2015\n1. Gerardin  P et al, PLoS  Medicine 2008\nChikungunya and young infants\nYoung infants infected via \nmosquito -borne transmission \nalso at risk for severe disease, particularly during the first few months of life\nClinical presentations similar to those with neonatal infections \nValamparampil  JJ et al, Ind J Ped 2009\nGupta D et al, Ind J Ped 2015\nVaccination during pregnancy: Immunogenicity\nNo data available on immunologic response to chikungunya vaccine \nadministered to pregnant individual \nGeneral principles and experience with other vaccines\n–Transplacental transfer of antibodies after maternal immunization demonstrated \nto confer protection with most vaccines\n–Examples of benefits include decreased rates of hospitalization in infants born to \nvaccinated women (e.g., influenza, COVID -19, RSV vaccines) and decreased risk \nfor preterm birth (e.g., COVID -19 vaccine)\nVaccination during pregnancy: Safety \nData are insufficient to determine whether any safety risks from vaccination \nduring pregnancy\n–Pregnancy was an exclusion criteria in clinical trials\n–Only two pregnant persons inadvertently vaccinated during pregnancy\nTwo pregnant persons vaccinated during 1st trimester\n–36-year -old: spontaneous abortion 59 days after vaccination at gestational age        \n~10– 14 weeks\n–23-year -old: anembryonic pregnancy noted at 53 days, spontaneous abortion at 55 \ndays after vaccination at ~8 weeks gestation\nGeneral notes on cases\n–Anembryonic pregnancies generally result from chromosomal problem at conception\n–Estimated 20%– 25% of all pregnancies lead to pregnancy loss, with highest rates in \n1st trimester and increasing rates with increasing maternal age \nKey language related to pregnancy in package insert1\nNoted under “Warnings and Precautions”\n–Vertical transmission of wild-type  chikungunya virus from pregnant individuals with \nviremia at delivery is common and can cause potentially fatal chikungunya virus \ndisease in neonates. Vaccine  viremia occurs in the first week following administration \nof chikungunya vaccine….it is not known if the vaccine virus can be vertically transmitted and cause fetal or neonatal adverse reactions\nNoted under “Use in Specific Populations”\n–A decision to administer chikungunya vaccine during pregnancy should take into consideration the individual’s risk of wild -type chikungunya virus infection, \ngestational age, and risks to the fetus or neonate from vertical transmission of wild -\ntype chikungunya virus....If neonates are born within 14 days of their mother receiving chikungunya vaccine, closely monitor them after birth for potential disease due to vaccine virus\n1. FDA. Package Insert –  IXCHIQ. Available at: https://www.fda.gov/vaccines -blood -biologics/ixchiq\nViremia after vaccination\nIn Phase 1 clinical trial\n–Viremia after vaccination assessed by quantitative reverse transcription-\npolymerase chain reaction ( qRT-PCR)\n–Plasma tested on days 3, 7, and 14 after vaccination\nAmong 30 subjects vaccinated with vaccine dose with equivalent amount \nof attenuated chikungunya virus as in licensed vaccine, viremia detected in \n–90% on day 3\n–17% on day 7\n–0% on day 14 \nFor many live vaccines, pregnancy is contraindication  \n–Theoretical risk to fetus from maternal viremia and viral transmission to fetus\n–MMR and varicella vaccines contraindicated during pregnancy, although no \ncases of congenital rubella or varicella syndrome or abnormalities attributable to fetal infection observed among infants born to women inadvertently vaccinated during pregnancy\nFor some live vaccines, pregnancy is precaution  \n–Vaccines can be used after considering the risks of disease and risks and benefits of vaccination\n–Yellow fever, dengue vaccines\nKroger A et al. General Best Practice Guidance for Immunization (https://www.cdc.gov/vaccines/hcp/acip -recs/general -recs/index.h tml) Live, attenuated vaccines and pregnancy: \nACIP General Best Practice Guidelines for Immunization \nGroups for whom clinical guidance will be relevant\nTravelers and laboratory workers \nPersons in U.S. territories and states with risk of chikungunya virus \ntransmission\nObjectives of vaccinating pregnant individuals\nProtect pregnant person from chikungunya virus infection\nAvoid maternal infection around time of delivery to prevent \nintrapartum virus transmission and severe disease in newborn\nTransplacental transfer of antibodies might also protect young infant from mosquito -borne transmission and severe disease\nProposed clinical guidance for use of chikungunya \nvaccine in pregnant individuals (1)\nPregnant individuals should avoid the risk for chikungunya virus infection, if possible \n(e.g., by avoiding travel to an area with virus transmission particularly during an outbreak). \nProposed clinical guidance for use of chikungunya \nvaccine in pregnant individuals (2)\nPregnancy is a precaution for vaccination with the live attenuated chikungunya \nvaccine. In general, vaccination should be deferred until after delivery. However, when the risk of infection is high and exposure cannot be avoided, a health care provider should discuss with a pregnant person the potential risks of chikungunya virus infection and the potential benefits and risks of vaccination so that vaccination can be considered. \nProposed clinical guidance for use of chikungunya \nvaccine in pregnant individuals (3)\nIf pregnant persons choose to be vaccinated, out of caution vaccination should \ngenerally be avoided during the 1st trimester (until 14 weeks gestation)  and after the \n36th week of gestation. \noAvoiding vaccination during the 1st trimester is preferred for two reasons. Firstly, \npregnancy loss has been reported in two individuals vaccinated during the 1st \ntrimester, although one was an anembryonic pregnancy. In addition, the vaccine is \nreactogenic and can cause fever, and fever has been linked to birth defects in the \n1st trimester. \noAvoidance of vaccination after the 36th week of gestation is to limit the risk of \nvaccine -induced viremia occurring in the intrapartum period and thus to reduce \nthe theoretical risk for perinatal transmission and potential adverse outcomes.*\n*Vaccine viremia is considered to occur in most individuals in the first few days after vaccination and to decrease thereafte r; \nviremia was no longer detectable in any clinical trial subjects at 14 days after vaccination. \nProposed clinical guidance for use of chikungunya \nvaccine in pregnant individuals (4)\nIn line with common practice following vaccination with live vaccines, non -pregnant \nvaccine recipients should generally wait 4 weeks before becoming pregnant. If a \npregnant person is inadvertently vaccinated outside of the preferred period or becomes pregnant within 4 weeks after chikungunya vaccination, this should not be considered a reason to terminate the pregnancy. \nThis guidance is intended to maximize the benefits of vaccination while minimizing \nrisks associated with vaccination during pregnancy.\nGuidance that maximizes benefits of vaccination while \nminimizing risks associated with vaccination during pregnancy\n1. Avoid risk if possible\n2. In general, defer vaccination until after delivery\n3. If exposure risk high, consider vaccination given risk for severe adverse \noutcomes of infection particularly if intrapartum transmission occurs\n4. If consider vaccination, where possible avoid 1st trimester and after 36th \nweek of gestation\nClinical guidance for use of live attenuated \nchikungunya vaccine in breastfeeding individuals\nChikungunya and breastfeeding\nChikunguny a viral ribonucleic acid (RNA) detected in breast milk on \nvery rare occasions1,2\n–No studies have reported detection of replicating virus\nCase report describing mother with chikungunya and chikungunya \nvirus RNA detected in her breast milk was breastfeeding her 3 -\nmonth -old infant1 \n–No symptoms or laboratory evidence of infection in infant\n1. Campos GS et al, Pediatr  Infect Dis J 2017; 2. De Paula Souza et al, Transl  Res 2023.  \nChikungunya vaccine and breastfeeding\nNo human data on whether chikungunya vaccine virus or antibodies are \npresent in breast milk after vaccination\nNeonates and other infants aged <1 year are at risk for severe disease if infected with wild -type chikungunya virus\n–Vaccine virus is attenuated, but outcome if chikungunya vaccine virus was \ntransmitted by breastfeeding unknown\nKey language related to lactation in package insert1 \nBreastfeeding is neither contraindication nor precaution for vaccination\nDevelopmental and health benefits of breastfeeding should be \nconsidered along with the mother's clinical need for the vaccine and any \npotential adverse effects on the breastfed child from the vaccine or from \nthe mother’s susceptibility to chikungunya\nVaccine viremia occurs after vaccination…the potential for transmission of vaccine virus from mother to infant through breastmilk is unknown\n1. FDA. Package Insert –  IXCHIQ. Available at: https://www.fda.gov/vaccines -blood -biologics/ixchiq\nLive attenuated vaccines and breastfeeding: \nACIP General Best Practice Guidelines for Immunization \nAlthough live viruses in vaccines can replicate in mother, majority of live \nviruses in vaccines have been shown not to be excreted in milk\n–Varicella vaccine virus has not been detected in human milk\n–Rubella vaccine virus has been detected in human milk, but virus usually does \nnot infect infant, and if infection occurs, the attenuated virus is well tolerated \nLive vaccines considered to be safe for administration to breastfeeding \nindividuals with two exceptions: \n–Yellow fever vaccine: three breastfed infants developed encephalitis after mother \nvaccinated\n–Smallpox vaccine (ACAM2000): theoretical risk for contact transmission from mother to infant\nKroger A et al. General Best Practice Guidance for Immunization (https://www.cdc.gov/vaccines/hcp/acip -recs/general -recs/index.h tml) \nACIP breastfeeding guidance for other live vaccines\nMMR: Not a precaution or contraindication \nVaricella: Not a precaution or contraindication\nYellow fever: Precaution \nSmallpox (ACAM2000): Contraindication\nGroups for whom clinical guidance will be relevant\nTravelers and laboratory workers \nPersons in U.S. territories and states with risk of chikungunya virus \ntransmission\nObjectives of vaccinating breastfeeding individuals\nProtect breastfeeding individual \nAdded benefit might be reduction in risk for infant through transfer \nof protective antibodies in breast milk\nProposed clinical guidance for use of chikungunya \nvaccine in breastfeeding individuals\nBreastfeeding individuals and their infants should avoid the risk for chikungunya virus \ninfection, if possible (e.g., by avoiding travel to an area with transmission particularly during an outbreak). \nIn the absence of data, breastfeeding is a precaution for vaccination. When the risk \nof infection is high (e.g., during an outbreak) and exposure cannot be avoided, a health care provider should discuss with a breastfeeding individual the developmental and health benefits of breastfeeding for the infant, the risks of chikungunya virus infection, and the potential benefits and risks of vaccination, and offer the vaccine to the breastfeeding person. At the current time, the data are insufficient to make a recommendation to defer breastfeeding for any period after \nvaccination. \nAcknowledgements\nDana Meaney -Delman\nNicole Lindsey\nErin Staples\nACOG and AAP members for their review of draft clinical guidance \nChikungunya Vaccines Work Group members", "summary": "National Center for Emerging and Zoonotic Infectious Diseases CLINICAL GUIDANCE FOR USE OF LIVE ATTENUATED  CHIKUNGUNYA VACCINE AMONG PREGNANT AND  BREASTFEEDING INDIVIDUALS Susan Hills, MBBS, MTH CDC Lead , Chikungunya Vaccines Work Group Arboviral Diseases Branch Division of Vector -Borne Diseases Fort Collins, Colorado    ACIP meeting, February 28, 2024 Clinical guidance for use of live attenuated  chikungunya vaccine in pregnant individuals Presentation of chikungunya among pregnant…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-28-29-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-02-28-29/05-Chikungunya-hills-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 28}
{"title": "01 DT Hughes Santoli 508", "content": "National Center for Immunization & Respiratory Diseases\nVFC Resolution Update: Tetanus and Diphtheria Toxoid Containing Vaccines\nMichelle Hughes\nDivision of Bacterial Diseases\nNational Center for Immunization and \nRespiratory DiseasesJeanne Santoli\nImmunization Services Division\nNational Center for Immunization and \nRespiratory Diseases\nFebruary 2024\nBackground\nBackground\n•CDC recommends a primary series of 5 DTaP vaccines for children <7 \nyears\n•For children aged <7 years who developed a contraindication to pertussis -containing vaccines, CDC previously recommended DT instead \nof DTaP\n•The sole DT vaccine manufacturer in the U nited States  discontinued DT \nproduction \n•Last lot expired in April 2023\n•No DT vaccin e is av ailable in the United States\nContraindication specific to pertussis vaccine \ncomponent\n•The only contraindication specific to the pertussis component in DTaP is \nencephalopathy within 7 days of vaccination, not attributed to another cause.\n•Exact numbers are unknown, but occurrence of this adverse reaction is extremely rare.\n•CDC issued updated vaccination guidance for young children with a contraindication to pertussis -containing vaccines.\nGuidance\n•CDC recommends young children receive DTaP as the first dose in the \ndiphtheria, tetanus, and pertussis childhood vaccination series. \n•CDC recommends continued use of DTaP unless a contraindication to pertussis -containing vaccines develops. \n•For young children who develop a contraindication to pertussis -\ncontaining vaccines, vaccine providers may administer Td for all recommended remaining doses in place of DTaP .\nUncertain impact on diphtheria protection\n•Td is licensed for ages ≥7 years \n•Td contains a lower dose of diphtheria toxoid compared to DT\n•Limited data suggest that low -dose diphtheria toxoid -containing \nvaccines may not reliably generate a protective diphtheria \nseroresponse.\nhttps://www.cdc.gov/vaccines/vpd/dtap- tdap -td/hcp/td- offlabel.html\n\nVFC Resolution Updates\n•MassBiologics  has discontinued production of their Td vaccine, TdVax.TM Grifols, who is the \nexclusive distributor for TdVax,TM expects to have product available through approximately \nJune 2024.  \n•Sanofi, who manufacturers Tenivac ,® the only other US- licensed Td vaccine, is taking steps to \naugment their available supply of Td for the US.  However, it is anticipated that the supply of \nTd vaccine in the US market will be constrained during 2024.  Temporary ordering controls \nhave been put into place in the public and private sectors to help manage the gap in supply.  \n•Tdap vaccine is available from both US- licensed manufacturers without supply constraints at \nthis time. \n•Based on the rarity of developing a contraindication to pertussis -containing vaccines,  the \ntemporarily constrained supply of Td vaccine is not anticipated to prevent providers from \nutilizing Td vaccine for these children in the VFC program. Td Vaccine Supply Update\nThe purpose of this resolution is to (1) add Td vaccine for use in children < 7 years of \nage for whom receipt of the pertussis component is contraindicated and to (2) update the language regarding the Tdap booster to align with ACIP recommendations. Purpose of the Resolution\nChildren and adolescents aged 6 weeks through 18 years. Eligible Groups\nVaccines containing tetanus toxoid, diphtheria toxoid, and acellular pertussis antigens \nrecommend for use in persons aged <7 years.Recommended Schedule and Intervals (1)\nVaccine Type Vaccine Brand (1) Age for approved use in the \nroutine schedule (2)\n2 mos 4 \nmos6 \nmos15-18 \nmos4-6 yrs \n(3)\nDTaP DTaP (4) Daptacel X X X X X \nDTaP (4) Infanrix X X X X X \nCombination \nvaccines with \nDTaPDTaP -HepB- IPV (4, 5) Pediarix X X X\nDTaP -IPV/Hib (4, 6) Pentacel X X X X\nDTaP -IPV-Hib-HepB (4, \n7)  Vaxelis X X X\nDTaP -IPV (8) Kinrix X\nDTaP -IPV (8) Quadracel X \nTd Td (9) Tenivac  X X X X \nTd Td (9) TdVax  X X X X \n(1)The use of brand names is not meant to preclude the use of other comparable licensed \nvaccines.\n(2)Minimal intervals: Dose 1 to 2: 4 weeks. Dose 2 to 3: 4 weeks. Dose 3 to 4: 6 months. Dose 4 to 5: 6 months. For more information on age for use in catch -up immunization schedules please \nsee: https://www.cdc.gov/vaccines/schedules/hcp/imz/catchup.html\n  \n(3)The fifth dose is not necessary if the fourth dose was given after the fourth birthday.  \n(4)FDA-approved for use in infants as young as 6 weeks.\n(5)FDA-approved for use through age 6 years (prior to 7th birthday). The combined DTaP-HepB -IPV \nvaccine may be used when any component of the combination is indicated, and if the other \ncomponents are not contraindicated. Approved for the primary series only (Doses 1 -3). For \nadequate immune response, the last dose of hepatitis B vaccine should be given at ≥24 weeks \nof age and therefore this combination vaccine should not be administered as a complete \nprimary series on an accelerated schedule at 4 -week intervals for prevention of pertussis.  Recommended Schedule and Intervals (2)\n(6) FDA-approved for use through age 4 years (prior to 5th birthday). The combined DTaP-IPV/Hib \nvaccine may be used when any component of the combination is indicated, and if the other \ncomponents are not contraindicated. Approved for the primary series and first booster dose (Doses \n1-4). The combined DTaP -IPV/Hib vaccine is not indicated for children 5 years of age and older.\n(7) FDA-approved for use through age 4 years (prior to 5th birthday). The combined DTaP-IPV -Hib-\nHepB vaccine may be used when any component of the combination is indicated, and if other \ncomponents are not contraindicated.  Approved for the primary series only (Doses 1 -3). For \nadequate immune response, the last dose of hepatitis B vaccine should be given >24 weeks of age \nand therefore this combination vaccine should not be administered as a complete primary series \non an accelerated schedule at 4 -week intervals for prevention of pertussis.  \n(8) The combined DTaP -IPV vaccines may be used when any component of the combination is \nindicated, and if the other components  are not contraindicated. Only approved for the booster \ndose at age 4 through 6 years.  Earlier doses should use another vaccine.  \n(9) Use tetanus toxoid - and diphtheria toxoid-containing vaccine if encephalopathy not attributable to \nanother identifiable cause occurs within 7 days of administration of previous dose of pertussis -\ncontaining vaccine. For more information on the use of Td in children <7 please see: About Young \nChildren with a Contraindication to Pertussis -Containing Vaccines | CDCRecommended Schedule and Intervals (3)\nVaccines containing tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis \nantigens recommended for use in persons aged 7– 18 years. Recommended Schedule and Intervals (4)\nVaccine Type Brand\nTdap (1, 2, 3, 4) Adacel\nBoostrix\nTd (4, 5, 6) Tenivac\nTdVax\n(1)The use of brand names is not meant to preclude the use of other comparable licensed \nvaccines.\n(2)Persons aged 11 -18 years should receive a single booster dose of Tdap, preferably at a \npreventive care visit at ages 11- 12 years.  The booster dose is not necessary if the Tdap \ndose was given after the ninth birthday. \n(3)Catch -up immunization:  Persons aged 7- 18 years who have never been vaccinated \nagainst pertussis, tetanus, or diphtheria should receive a series of three tetanus and \ndiphtheria toxoid -containing vaccines, which includes at least 1 dose of Tdap. The \npreferred schedule is a dose of Tdap, followed by a dose of either Td or Tdap at least 4 \nweeks afterward and another dose of either Td or Tdap 6 to 12 months later. Persons \naged 7- 18 years who are not fully immunized against pertussis, tetanus, or diphtheria \nshould receive one dose of Tdap (preferably the first) in the catch -up series; if \nadditional tetanus toxoid -containing doses are required, either Td or Tdap vaccine can \nbe used. The catch -up immunization schedule and minimum intervals between doses \nare available at: https://www.cdc.gov/vaccines/schedules/hcp/child- adolescent.html  Recommended Schedule and Intervals (5)\n(4) Adolescents who are pregnant should receive Tdap, irrespective of past history of Tdap receipt. \nTdap should be administered from 27 through 36 weeks’ gestation, preferably during the earlier part of this time period, although it may be administered at any time during pregnancy. If an adolescent did not receive Tdap during her current pregnancy and did not receive a prior dose of Tdap ever, then Tdap should be administered immediately postpartum.  If an adolescent did not receive Tdap during her current pregnancy but did receive a prior dose of Tdap, then she should not receive a dose of Tdap postpartum. \n(5) Tetanus prophylaxis for wound management: A tetanus toxoid –containing vaccine is indicated as \npart of wound management if more than five years has passed since the last tetanus toxoid –\ncontaining vaccine dose. If a tetanus toxoid –containing vaccine is indicated for persons aged ≥11 \nyears, Tdap is preferred for persons who have not previously received Tdap or whose Tdap history is unknown. If a tetanus toxoid–containing vaccine is indicated for a pregnant woman, \nTdap should be used. For nonpregnant persons with documentation of previous vaccination with \nTdap, either Td or Tdap can be used if a tetanus toxoid–containing vaccine is indicated.\n(6) Td should be used if encephalopathy not attributable to another identifiable cause occurs within \n7 days of administration of a previous dose of pertussis -containing vaccine. Recommended Schedule and Intervals (6)\nRecommended Dosage\nRefer to product package inserts available at:\nhttps://www.fda.gov/vaccines -blood- biologics/vaccines/vaccines -licensed- use- united -\nstates  \nContraindications/PrecautionsContraindications and precautions can be found at:  https://www.cdc.gov/mmwr/volumes/67/rr/rr6702a1.htm\n Dosage and Contraindications/Precautions\n[If an ACIP recommendation regarding diphtheria, tetanus, and pertussis vaccination is \npublished within 6 months following this resolution, the relevant language above (except in the eligible groups sections) will be replaced with the language in the \nrecommendation and incorporated by reference to the publication URL.]  Statement Regarding Update Based on Published  \nDocuments", "summary": "National Center for Immunization & Respiratory Diseases VFC Resolution Update: Tetanus and Diphtheria Toxoid Containing Vaccines Michelle Hughes Division of Bacterial Diseases National Center for Immunization and  Respiratory DiseasesJeanne Santoli Immunization Services Division National Center for Immunization and  Respiratory Diseases February 2024 Background Background •CDC recommends a primary series of 5 DTaP vaccines for children <7  years •For children aged <7 years who developed a…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-28-29-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-02-28-29/01-DT-Hughes-Santoli-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 19}
{"title": "02 influenza Frutos 508", "content": "National Center for Immunization & Respiratory Diseases\nInterim Estimates of 2023–24 Seasonal Influenza Vaccine \nEffectiveness\nAaron M. Frutos, PhD, MPH\nOn behalf of CDC Influenza Vaccine Effectiveness Collaborators\nAdvisory Committee on Immunization Practices\nFebruary 28, 2024\nCDC Influenza Vaccine Effectiveness Networks\nFour networks to evaluate vaccine effectiveness (VE) against laboratory -\nconfirmed influenza for children, adolescents, and adults in the \noutpatient and inpatient settings \n3CDC Influenza Vaccine Effectiveness Networks\nInvestigating Respiratory Viruses in the Acutely Ill (IVY)\nNew Vaccine Surveillance Network (NVSN)\nU.S. Flu Vaccine Effectiveness Network (US Flu VE)\nVirtual SARS -CoV-2, Influenza, and Other respiratory viruses Network (VISION)\nVISION\nIVYNVSN\n4These networks include all ages across settings\nAgeSettingOutpatient \nclinic\nHospitalizationEmergency \ndepartment/ \nurgent careUS Flu VE\nAdults \n(≥18 years)Children and adolescents\n(6 months – 17 years)\nNVSN\n5NVSN: all settings\nAgeSettingOutpatient \nclinic\nHospitalizationEmergency \ndepartment/ \nurgent care\nAdults \n(≥18 years)Children and adolescents\n(6 months – 17 years)\nNVSN\n6US Flu VE: Outpatient clinic and ED/UC\nAgeSettingOutpatient \nclinic\nHospitalizationEmergency \ndepartment/ \nurgent careUS Flu VE\nAdults \n(≥18 years)Children and adolescents\n(6 months – 17 years)\nNVSN\n7VISION: ED/UC & hospitalization\nAgeSettingOutpatient \nclinic\nHospitalizationEmergency \ndepartment/ \nurgent careUS Flu VE\nAdults \n(≥18 years)Children and adolescents\n(6 months – 17 years)VISION\nIVY\n8IVY: hospitalization\nAgeSettingOutpatient \nclinic\nHospitalizationEmergency \ndepartment/ \nurgent care\nAdults \n(≥18 years)Children and adolescents\n(6 months – 17 years)\nIVY\n9US Flu VE: Outpatient clinic and ED/UC\nAgeSettingOutpatient \nclinic\nHospitalizationEmergency \ndepartment/ \nurgent care\nAdults \n(≥18 years)Children and adolescents\n(6 months – 17 years)US Flu VE\nIVY\n10VISION: ED/UC & hospitalization\nAgeSettingOutpatient \nclinic\nHospitalizationEmergency \ndepartment/ \nurgent care\nAdults \n(≥18 years)Children and adolescents\n(6 months – 17 years)US Flu VE\nVISION\nVISION\nIVYNVSN\n11These networks include all ages across settings\nAgeSettingOutpatient \nclinic\nHospitalizationEmergency \ndepartment/ \nurgent careUS Flu VE\nAdults \n(≥18 years)Children and adolescents\n(6 months – 17 years)Outpatient\n12CDC influenza VE networks include patients from 22 \nstates\nNVSN\nIVY\nUS Flu VE\nVISION\n\n132023- 2024 Influenza VE Methods\nEnrollees: Have acute respiratory illness \nDates of enrollment: Fall 2023-  Early 2024\nDesign: Test-negative design\n•Comparing vaccination odds among case patients with influenza confirmed by molecular assay \nversus control patients testing negative for influenza and SARS- CoV-2\n•Vaccination status: receipt of any 2023 –24 seasonal flu vaccine according to medical records, \nimmunization registries, claims data, and/or self -report\n142023- 2024 Influenza VE Methods\nAnalysis : VE = (1 – adjusted OR) x 100%\n•Adjusted for geographic region, age, calendar time of illness\n•IVY , US Flu VE, and VISION also adjusted for sex and race and ethnicity\n•US Flu VE also adjusted for days between illness onset and enrollment and self -reported \ngeneral health status. \n•VE estimates were calculated for influenza A subtypes A(H1N1)pdm09 and A(H3N2) when possible\n•Subtype not available for VISION\n•VE was not estimated for some age groups and settings when sample size was small or when \nmodels did not converge\nPediatric VE\n(aged 6 months –17 years)\n16Pediatric VE against any influenza\nInfluenza test result by influenza vaccination \nstatus, no. vaccinated/Total (%)\nInfluenza -positive Influenza -negative VE (95% CI)\nNVSN (Outpatient) 123/622 (20) 793/2,577 (31) 59 (48, 67)\nUS Flu VE (Outpatient) 29/283 (10) 182/736 (25) 67 (48, 80)\nVISION (Outpatient) 961/6,068 (16) 4,579/15,274 (30) 60 (57, 64)\nNVSN (Inpatient) 29/128 (23) 543/1,321 (41) 61 (40, 75)\nVISION (Inpatient) 21/113 (19) 299/921 (32) 52 (16, 72)\n17Pediatric VE against any influenza\n\n18Pediatric VE against influenza A\n\n19Pediatric VE against influenza A(H1N1)pdm09\n\n20Pediatric VE against influenza A(H3N2)\n\n21Pediatric VE against influenza B\n\nAdult VE\n(aged ≥18 years)\n23Adult VE against any influenza\nInfluenza test result by influenza vaccination \nstatus, no. vaccinated/Total (%)\nInfluenza -positive Influenza -negative VE (95% CI)\nUS Flu VE (Outpatient) 177/568 (31) 803/1,807 (44) 33 (16, 47)\nVISION (Outpatient) 4,501/18,385 (24) 21,356/52,657 (41) 49 (47, 51)\nIVY (Inpatient) 200/632 (32) 1,517/3,872 (39) 44 (32, 54)\nVISION (Inpatient) 728/1,839 (40) 7,425/14,168 (52) 41 (34, 47)\n24Adult VE against any influenza\n\n25Adult VE against influenza A\n\n26Adult VE against influenza A(H1N1)pdm09\n\n27Adult VE against influenza A(H3N2)\n\n28Adult VE against influenza B\n\nAdult (aged ≥65) VE\n30Adult (aged ≥65) VE against any influenza\nInfluenza test result by influenza vaccination \nstatus, no. vaccinated/Total (%)\nInfluenza -positive Influenza -negative VE (95% CI)\nUS Flu VE (Outpatient) 41/79 (52) 300/439 (68) 51 (14, 72)\nVISION (Outpatient) 1,944/3,687 (53) 12,162/19,571 (62) 41 (36, 45)\nIVY (Inpatient) 113/249 (45) 938/1,945 (48) 42 (23, 56)\nVISION (Inpatient) 531/1,066 (50) 6,058/10,118 (60) 42 (34, 50)\n31Adult (aged ≥65) VE against any influenza\n\n32Adult (aged ≥65) VE against influenza A\n\n33Adult (aged ≥65) VE against influenza B\n\nDiscussion\n35Summary of four CDC influenza VE networks\nVaccination with a 2023 -24 influenza vaccine reduced the risk  for medically \nattended influenza outpatient visits and hospitalizations  among children, \nadolescents, and adults across 22 US States\nVaccination was effective against both influenza A (mostly subtype \nA(H1N1)pdm09) and B (lineage Victoria) viruses  that have circulated this season\nResults were consistent across networks\nFor more information, contact CDC\n1-800- CDC- INFO (232- 4636)\nTTY:  1 -888- 232- 6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.\nAaron M. Frutos, PhD, MPH\nInfluenza Division\nNational Center for Immunization and Respiratory Diseases\nAFrutos@cdc.govWe’d like to thank our many \ncollaborators from CDC, IVY , NVSN, \nUS Flu VE, and VISIONThank you\n37Overall VE (pediatric and adults) by season*\n*Estimates are from US Flu VE except for 2022 -23 which are from a study from WI", "summary": "National Center for Immunization & Respiratory Diseases Interim Estimates of 2023–24 Seasonal Influenza Vaccine  Effectiveness Aaron M. Frutos, PhD, MPH On behalf of CDC Influenza Vaccine Effectiveness Collaborators Advisory Committee on Immunization Practices February 28, 2024 CDC Influenza Vaccine Effectiveness Networks Four networks to evaluate vaccine effectiveness (VE) against laboratory - confirmed influenza for children, adolescents, and adults in the  outpatient and inpatient settings …", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-28-29-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-02-28-29/02-influenza-Frutos-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 37}
{"title": "03 influenza Zhu 508", "content": "1Sophie Zhu, PhD, presenting on behalf of the study team\nEpidemic Intelligence Service Officer \nCalifornia Department of Public Health\nInfluenza VEData: Interviews, \nelectronic health records\nNew: California public \nhealth dataMultiple considerations for vaccine \neffectiveness (VE) calculation\nPopulations:\nPediatric, hospitalizedCare settings\n2\nNew requirements for data reporting in \nCalifornia\n•1/1/23: Influenza vaccination records  became \nreportable to the California Immunization \nRegistry (CAIR) \n3•6/15/23: All negative influenza results (in \naddition to previously reportable positive \ninfluenza results) became reportable to the \nCalifornia Reportable Disease Information \nExchange ( CalREDIE )\nCalifornia VE Calculation\nAttribute California\nData source Mandatory influenza results and influenza immunization records\nDate available VE estimates and data available each December or earlier\nOutcome(s) Laboratory -confirmed influenza using nucleic acid amplification \ntests (NAAT)\nPopulation(s) Californians tested for influenza using NAAT from diverse care \nsettings\n4\nMethods\n5\n•Inclusion criteria: California residents aged ≥6 months with molecular tests for \ninfluenza (A/B) captured by the state electronic laboratory reporting system\n•Dates: October 1, 2023 —January 31, 2024\n•Vaccination status: documented dose of seasonal influenza vaccine in CAIR ≥14 \ndays before testing\n•Deduplicate results for persons with multiple records\n•Remove results from laboratories weekly with ≥50% positive due to suspected \nunderreporting of negative results (<5% of data)\n•Analysis:  VE = (1 – adjusted OR) x 100%\n•Mixed -effects logistic regression model adjusted for age, race, ethnicity, \ntesting week (random effect), and county (random effect)\n6Methods: unmatched case -control study\nNumber of influenza detections by type and subtype detected in RLN \nlaboratories and percentage of specimens testing positive at clinical \nsentinel laboratories – 2023 -2024 season to date\n7\n\nOverall No. (%) Influenza positive No. (%) Influenza negative No. (%)\nTotal 678,422 (100) 77,501 (11.4) 600,921 (88.6)\nAge ( yrs, median) 42 (17 –66) 31 (10 –52) 44 (19 –68)\nRace\nAmerican Indian or Alaska Native\nAsian\nBlack or African American\nNative Hawaiian or Pacific Islander\nWhite\nMultiple Races\nOther\nUnknown2,919 (0.4)\n53,419 (7.9)\n40,069 (5.9)\n2,878 (0.4)\n301, 779 (44.5)\n1,381 (0.2)\n131,284 (19.4)\n144,693 (21.3)326 (0.4)\n6,252 (8.1)\n4,033 (5.2)\n300 (0.4)\n29,908 (38.5)\n130 (0.2)\n16,098 (20.8)\n20,454 (26.4)2,593(0.5)\n47,167 (7.8)\n36,036 (6.0)\n2,578 (0.4)\n271,871 (45.2)\n1,251 (0.2)\n115,186 (19.2)\n124,239 (20.7)\nEthnicity\nHispanic or Latino\nNot Hispanic or Latino\nUnknown159,676 (23.6)\n386,200 (56.9)\n132,546 (19.5)21,309 (27.4)\n38,653 (49.9)\n17,539 (22.7)138,367 (23.1)\n347,547 (57.8)\n115,007 (19.1)\nVaccinated\nOverall\nVaccinated during Oct. 1 –31\nVaccinated during Nov. 1 –30\nVaccinated during Dec. 1 –31\nVaccinated during Jan. 1 –31190,313 (28.1)\n11,073 (13.1)\n39,497 (25.3)\n69,884 (30.1)\n69,859 (33.9)13,905 (17.9)\n93 (6.5)\n1,357 (12.5)\n7,104 (17.6)\n5,351 (21.4)176,408 (29.3)\n10,980 (13.2)\n38,140 (26.3)\n62,780 (32.7)\n64,508 (35.6)Participant characteristics\n8\nInfluenza vaccines protect against laboratory -\nconfirmed influenza\nInfluenza positive Influenza negative Adjusted VE*\nTotal Vaccinated no. \n(%)Total Vaccinated no. \n(%)% (95% CI)\nInfluenza A and B**\nOverall 75,876 13,629 (18) 600,921 176,408 (29) 45 (44 –46)\n<18 years 28,914 3,744 (13) 147,047 32,791 (22) 56 (54 –57)\n18–49 years 26,435 3,334 (13) 189,129 36,171 (19) 48 (46 –50)\n50–64 years 10,861 2,575 (24) 96,148 28,579 (30) 36 (33 –39)\n≥65 years 9,666 3,976 (41) 168,597 78,867 (47) 30 (27 –33)\nStudy period: October 1, 2023 – January 31, 2024.\n*VE was estimated using an unmatched case -control study as 100% x (1 -aOR) where aOR is the ratio of odds of vaccination among influenza \npositive cases versus influenza negative controls. ORs were estimated using mixed -effects logistic regression with adjustment fo r age, race, \nethnicity as fixed effects and enrollment week and county of residence as random effects.\n**VE for unknown influenza types was not calculated because of small sample size, and unknown influenza type results were exclu ded from \noverall influenza A and B VE estimation.\n9\nVE against influenza A was lower but still \nprotective in all age groups\nInfluenza positive Influenza negative Adjusted VE*\nTotal Vaccinated no. \n(%)Total Vaccinated no. \n(%)% (95% CI)\nInfluenza A\nOverall 68,716 13,118 (19) 600,921 176,408 (29) 42 (41 –43)\n<18 years 25,393 3,517 (14) 147,047 32,791 (22) 52 (51 –53)\n18–49 years 23,257 3,136 (14) 189,129 36,171 (19) 44 (42 –46)\n50–64 years 10,546 2,532 (24) 96,148 28,579 (30) 35 (32 –38)\n≥65 years 9,520 3,933 (41) 168,597 78,867 (47) 29 (26 –32)\nStudy period: October 1, 2023 – January 31, 2024.\n*VE was estimated using an unmatched case -control study as 100% x (1 -aOR) where aOR is the ratio of odds of vaccination among influenza \npositive cases versus influenza negative controls. ORs were estimated using mixed -effects logistic regression with adjustment fo r age, race, \nethnicity as fixed effects and enrollment week and county of residence as random effects.\n10\nVE against influenza B was highly protective \nacross most age groups\nInfluenza positive Influenza negative Adjusted VE*\nTotal Vaccinated no. \n(%)Total Vaccinated no. \n(%)% (95% CI)\nInfluenza B\nOverall 7,160 511 (7) 600,921 176,408 (29) 76 (73 –78)\n<18 years 3,521 227 (6) 147,047 32,791 (22) 79 (76 –82)\n18–49 years 3,178 198 (6) 189,129 36,171 (19) 75 (71 –78)\n50–64 years 315 43 (14) 96,148 28,579 (30) 67 (55 –76)\n≥65 years 146 43 (29) 168,597 78,867 (47) 54 (33–67)\nStudy period: October 1, 2023 – January 31, 2024.\n*VE was estimated using an unmatched case -control study as 100% x (1 -aOR) where aOR is the ratio of odds of vaccination among influenza \npositive cases versus influenza negative controls. ORs were estimated using mixed -effects logistic regression with adjustment fo r age, race, \nethnicity as fixed effects and enrollment week and county of residence as random effects.\n11\nCumulative VE — Oct. 1, 2023 –Jan. 31, 2024\nInfluenza positive Influenza negative Adjusted VE*\nTotal Vaccinated no. \n(%)Total Vaccinated no. \n(%)% (95% CI)\nInfluenza A and B**\nOctober 31st 1,455 93 (6) 83,403 11,021 (13) 46 (34, 57)\nNovember 30th 11,703 1,376 (12) 223,921 47,682 (21) 51 (48, 54)\nDecember 31st 53,181 8,695 (16) 416,136 110,816 (27) 47 (46, 48)\nOverall (January 31st) 75,876 13,905 (18) 600,921 176,408 (29) 45 (44, 46)\n*VE was estimated using an unmatched case -control study as 100% x (1 -aOR) where aOR is the ratio of odds of vaccination among influenza \npositive cases versus influenza negative controls. ORs were estimated using mixed -effects logistic regression with adjustment fo r age, race, \nethnicity as fixed effects and enrollment week and county of residence as random effects.\n**VE for unknown influenza types was not calculated because of small sample size, and unknown influenza type results were exclu ded from \noverall influenza A and B VE estimation.\n12\nLimitations\n1.Likely incomplete documentation and reporting of mandatory vaccination and \ntesting\n2.Cannot assess partial/full vaccination status for children aged <9 years\n3.Lack of symptom information, test setting, and outcome status (illness, \nhospitalization, or death)\n4.Potential lack of generalizability across the US\n5.Subtype information not available for positive influenza results\n6.Lack of control for other confounders (health seeking behavior, pre -existing \nconditions)\n13\nSummary\n•Current seasonal influenza vaccines provide protection against \nlaboratory -confirmed influenza for persons aged ≥6 months\n•Higher VE for influenza B & younger age groups (<18 years, 18 -49 \nyears)\n•Mandatory public health data can be leveraged to calculate timely in -\nseason influenza effectiveness as an additional estimate supporting \nexisting public health influenza efforts including vaccination messaging\n•Useful to promote additional prevention measures prior to peak\n•Prepare for increased hospital capacity\n14\nAcknowledgments\nCDPH Division of Communicable Disease Control\nJoshua Quint*\nTomás M. León*\nMonica Sun*\nNancy J. Li*\nSeema Jain*\nCora Hoover*\nRobert Schechter*\nErin L. Murray* \nTimothy Lo\nCeleste Romano\n15CDC NCIRD\nMark Tenforde*\nJessie Chung\nSascha Ellington\n*co-authorCalifornia’s local \nhealth \ndepartments", "summary": "1Sophie Zhu, PhD, presenting on behalf of the study team Epidemic Intelligence Service Officer  California Department of Public Health Influenza VEData: Interviews,  electronic health records New: California public  health dataMultiple considerations for vaccine  effectiveness (VE) calculation Populations: Pediatric, hospitalizedCare settings 2 New requirements for data reporting in  California •1/1/23: Influenza vaccination records  became  reportable to the California Immunization  Registry…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-28-29-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-02-28-29/03-influenza-Zhu-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 15}
{"title": "04 influenza Creech 508", "content": "Safety of Live Attenuated \nInfluenza Vaccine in \nChildren with Asthma\nC. Buddy Creech, MD, MPH\nEdie Carell Johnson Chair and Professor, Pediatric Infectious Diseases\nDirector, Vanderbilt Vaccine Research Program\nVanderbilt University Medical Center\nNashville, Tennessee\nAdvisory Committee on Immunization Practices (ACIP) Meeting\nFebruary 28, 2024\nDisclaimer\n•The findings and conclusions in this presentation are those of the presenter and \ndo not necessarily represent the official position of the Centers for Disease Control and Prevention\n•Mention of a product or company name is for identification purposes only and does not constitute endorsement by CDC\n•This study was supported by the CDC Clinical Immunization Safety Assessment (CISA) Project \n•Dr. Creech reports the receipt of consulting fees from Pfizer, Moderna, Sanofi, GSK, TD Cowen Investments, and CommenseBio ; grant support from Moderna; \nand royalties from UpToDate. None are related specifically to influenza vaccines or asthma\n2\nDuke University\nAmy Stallings, MD\nChris Todd, MPH\nSue Doyle, LPN\nLynn Harrington, RN, BSNLori Hendrickson, RN, BSNBeth Patterson, RN, BSN\nLuis Ballon\nJoyce Gandee\nErica SuarezCincinnati Children’s Hospital\nMary Allen Staat , MD, MPH\nCarolyn Kercsmar , MD\nMarilyn Rice, MSValerie Sackenheim , RN, CPN\nJoe Sorter, BAJeanne Kleiman, BS, ALC, CCRPVanderbilt University Medical Center\nC. Buddy Creech, MD, MPHAndrew Sokolow, MD\nKathryn Edwards, MD\nNatalia Jimenez, PhD, MSCIShanda Phillips, RN, BSNKate Sokolow, RN, MSN\nBraxton Hern, BS\nPaula Campbell, MPHYuwei Zhu, MDCDC \nKaren Broder, MDTheresa Harrington, MD, MPHTM (retired)\nFrank DeStefano, MD, MPH (retired) \nLisa Grohskopf , MD, MPH\nOidda  Museru , RN, MPH\nSuzanne Beavers, MD A. Patricia Wodi, MD \n\nBottom Line, Up Front\nIn a study of 142 children \nwith persistent asthma, \nLAIV4 was not associated  with \nincreased frequency of asthma \nexacerbations, increase in asthma -\nrelated symptoms, or decrease in \npeak expiratory flow rate (PEFR) \nin the 6 weeks following vaccination\n4\n\nAnn Allergy Asthma \nImmunol 2017\nVaccines 2017\nIn these studies, children with asthma who received LAIV were not found \nto have a higher incidence of lower respiratory events\nJACI 2020\n6Study Population: \n5 – 17-year -old \nchildren with \npersistent asthma\nPrimary Objective and Definitions\nTo compare the proportion of participants experiencing an asthma \nexacerbation during the 42 days after LAIV4 vs. IIV4\n•Scientific Hypothesis: LAIV4 is non-inferior to IIV4\n•Null Hypothesis: Expressed statistically, the hypothesis was that the proportion of \nchildren experiencing an asthma exacerbation in the LAIV4 group would be ≥10% higher than the proportion in the IIV4 group.\nPersistent Asthma: Provider diagnosis of asthma + prescription of a long -\nacting controller medication\n•Note: This is distinct from intermittent asthma , in which children may have \nintermittent, mild symptoms or require infrequent doses of albuterol\nAsthma Exacerbation : An acute episode of progressively worsening \nshortness of breath, cough, wheezing, chest tightness, or respiratory distress \nfor which the patient seeks medical attention or receives a new prescription for systemic corticosteroids.  \n7\nRelevant Exclusion Criteria\n•Acute illness (with or without fever) within 72 hours of enrollment or use \nof antipyretics within 24 hours led to a temporary delay in vaccination \n•Recent receipt of inactivated vaccine (14 days) or live vaccine (28 days) or planned receipt of any vaccine within 42 days of vaccination\n•Children with immunosuppression, including those who had received 20 mg of prednisone (or greater) for more than 14 days in the previous month, were excluded. \n•Children who had a life- threatening exacerbation in the previous 2 years or \nany exacerbation in the month prior to enrollment\n•Use of influenza- specific antiviral medication within 48 hours of enrollment\n•Currently receiving aspirin\n8\nAdditional Eligibility Issues\nPost -menarchal  females had urine or serum pregnancy testing prior to \nenrollment\nFor children 5 -8 years of age who required two doses of vaccine based \nupon ACIP recommendations, enrollment could occur after either the \nfirst or the second dose of vaccine.\n•If enrollment occurred after the first dose, the study staff instructed the \nfamily to delay 2nd vaccination until after study follow- up was completed \nunless widespread influenza disease activity was detected in the community.\n9\n10\n\n11\n70% of participants were classified as having moderate or severe asthma\nThere were slightly more males than females (p=0.5)Black individuals comprised >30% of the study population; approximately 5% were Hispanic or Latino\nIn the 14 days following vaccination, we observed 3 exacerbations \namong LAIV4 recipients and 4 in IIV4 recipients (3.9% vs. 5.7%, p=0.74)\nIn the 42 days following vaccination, we observed 8 exacerbations in \nthe LAIV4 group and 10 in the IIV4 group (10.8% vs. 14.7%, p=0.71)\n12\nGiven that the upper bound for non- inferiority was 10% (0.1), a difference in \nproportion of - 3.9% (CI: 90% CI:  - 0.15, 0.07) means that we can reject the null \nhypothesis that LAIV4 is inferior to IIV4. \nLAIV4 was not associated with increased asthma symptoms\n13\nNo significant differences were seen when \ncomparing across age groups (5 -11 years of \nage, 12 -17 years of age), study site, or \nasthma severity (mild/moderate vs. severe)\nPEFR: Peak Expiratory Flow Rate\nMyalgia and sore throat were more common in IIV4 recipients\nStrengths and Limitations of the Study\nStrengths\n•Multicenter, prospective, randomized, and controlled\n•Enriched for children with persistent asthma and those with moderate to severe asthma\n•Captured asthma symptoms in addition to asthma exacerbations and medical utilization\n•Captured reactogenicity data\n•Enrolled over two influenza seasons, increasing generalizability\nLimitations\n•Enrolled fewer participants than originally intended, but posterior power calculations revealed \nadequate power (79%) to detect differences between groups\n•Enrolled over two influenza seasons, leading to slightly different products\n15\nSummary and Conclusions\nLAIV4 was not associated with increased asthma symptoms or \nasthma exacerbations in the 14 - or 42 -days following immunization\nRates of reactogenicity were similar between IIV4 and LAIV4, though myalgia and sore throat were more common in the IIV4 arm\nLAIV4 may be a suitable option for children ≥5 years with asthma, including moderate to severe asthma\n16\nDuke University\nAmy Stallings, MD\nChris Todd, MPH\nSue Doyle, LPN\nLynn Harrington, RN, BSNLori Hendrickson, RN, BSNBeth Patterson, RN, BSN\nLuis Ballon\nJoyce Gandee\nErica SuarezCincinnati Children’s Hospital\nMary Allen Staat , MD, MPH\nCarolyn Kercsmar , MD\nMarilyn Rice, MSValerie Sackenheim , RN, CPN\nJoe Sorter, BAJeanne Kleiman, BS, ALC, CCRPVanderbilt University Medical Center\nC. Buddy Creech, MD, MPHAndrew Sokolow, MD\nKathryn Edwards, MD\nNatalia Jimenez, PhD, MSCIShanda Phillips, RN, BSNKate Sokolow, RN, MSN\nBraxton Hern, BS\nPaula Campbell, MPHYuwei Zhu, MDCDC\nKaren Broder, MDTheresa Harrington, MD, MPHTM (retired)\nFrank DeStefano, MD, MPH (retired) \nLisa Grohskopf , MD, MPH\nOidda Museru, RN, MPHSuzanne Beavers, MD A. Patricia Wodi, MD \n\nDiscussion  \n18", "summary": "Safety of Live Attenuated  Influenza Vaccine in  Children with Asthma C. Buddy Creech, MD, MPH Edie Carell Johnson Chair and Professor, Pediatric Infectious Diseases Director, Vanderbilt Vaccine Research Program Vanderbilt University Medical Center Nashville, Tennessee Advisory Committee on Immunization Practices (ACIP) Meeting February 28, 2024 Disclaimer •The findings and conclusions in this presentation are those of the presenter and  do not necessarily represent the official position of…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-28-29-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-02-28-29/04-influenza-Creech-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 18}
{"title": "05 influenza grohskopf 508", "content": "National Center for Immunization & Respiratory Diseases\nInfluenza B/Yamagata Update\nLisa Grohskopf, MD, MPH\nAdvisory Committee on Immunization Practices\nFebruary 28, 2024\n•Quadrivalent influenza vaccines introduced in 2013 -14 to provide broader coverage \nof influenza B viruses.\n–Quadrivalents contain one influenza B virus from each lineage (Victoria and Yamagata).\n–Transition from trivalents to quadrivalents complete by the 2021 -22 influenza season.\n•No confirmed influenza B/Yamagata viruses in global surveillance since March 2020.\n•WHO and the FDA Vaccines and Related Biological Products Advisory Committee \n(VRBPAC) have recommended excluding B/Yamagata from influenza vaccines.\n•WHO has made recommendations for Northern Hemisphere 2024 -25 vaccines.\n–Decisions regarding composition are made by individual national regulatory authorities.\n•VRBPAC to discuss composition of 2024- 25 U.S. influenza vaccines on March 5, 2024. Influenza B/Yamagata and 2024 -25 Influenza Vaccines\n2Recommended composition of influenza virus vaccines for use in the 2024 southern hemisphere influenza season (who.int)\nVaccines and Related Biological Products Advisory Committee October 5, 2023 Meeting Announcement - 10/05/2023 | FDA\nRecommended composition of influenza virus vaccines for use in the 2024 -2025 northern hemisphere influenza season (who.int)\nVaccines and Related Biological Products Advisory Committee March 5, 2024 Meeting Announcement - 03/05/2024 | FDA\nFor more information, contact CDC\n1-800- CDC- INFO (232- 4636)\nTTY:  1 -888- 232- 6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.", "summary": "National Center for Immunization & Respiratory Diseases Influenza B/Yamagata Update Lisa Grohskopf, MD, MPH Advisory Committee on Immunization Practices February 28, 2024 •Quadrivalent influenza vaccines introduced in 2013 -14 to provide broader coverage  of influenza B viruses. –Quadrivalents contain one influenza B virus from each lineage (Victoria and Yamagata). –Transition from trivalents to quadrivalents complete by the 2021 -22 influenza season. •No confirmed influenza B/Yamagata viruses…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-28-29-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-02-28-29/05-influenza-grohskopf-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 3}
{"title": "01 POLIO Brooks 508", "content": "Centers for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation use. No rights  are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.Polio Vaccine Work Group\nOliver Brooks, MD, FAAP\nACIP Meeting\nFebruary 28, 2024\n\nnOPV2\n▪Considerations for the potential use of novel type 2 oral poliovirus \nvaccine (nOPV2) as an outbreak control measure in the United States\nfIPV\n▪Clinical considerations for children who received fractional dose \ninactivated polio vaccine ( fIPV) in other countriesPolio Vaccination Work Group Terms of Reference\nPolicy topics under consideration:", "summary": "Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-28-29-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-02-28-29/01-POLIO-Brooks-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 2}
{"title": "02 POLIO Kidd 508", "content": "Centers for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation use. No rights  are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.Considerations for the Potential Use of Novel Type 2 Oral \nPoliovirus Vaccine (nOPV2) as an Outbreak Control \nMeasure in the United States\nSarah Kidd, MD, MPH\nACIP Meeting\nFebruary 28, 2024\n\n▪ACIP voting members\n–Oliver Brooks (Chair)\n–Lynn Bahta\n–Sybil Cineas\n▪Liaisons\n–Lynn Fisher, American Academy of Family Physicians\n–Chandy C. John, American Academy of Pediatrics \n–Sandra Fryhofer , American Medical Association\n–Kathy Kudish, Association of Immunization Managers\n–Marcus Plescia , Association of State and Territorial Health Officials\n–Paul R. Cieslak , Council of State and Territorial Epidemiologists\n–Christine Hahn, Council of State and Territorial Epidemiologists\n–Tina Q. Tan, Infectious Diseases Society of America\n–Adenike  Shoyinka , Infectious Diseases Society of America\n–Mary Wilson, International Society of Travel Medicine\n–Jaqueline Lawler, National Association of County and City Health Officials\n–Kathy Edwards, Pediatric Infectious Diseases Society\n–Joseline Zafack , Public Health Agency of Canada*Polio Work Group Members\n*In the event of a Work Group poll, CDC, FDA, and Public Health Agency of Canada members are not included.▪Consultants\n–Edwin Asturias\n–Doug E Campos -Outcalt *\n–Emily Lutterloh\n–Jennifer Rosen\n–Eli Rosenberg\n▪FDA*\n–Robin Levis\n▪CDC*\n–Cara Burns\n–Thomas Clark\n–Miranda Delahoy\n–Brian Edlin\n–Concepcion Estivariz\n–Halle Getachew\n–Sarah Kidd\n–Janelle King\n–Adriana Lopez\n–M. Steve Oberste\n▪Poliovirus infection can cause \npoliomyelitis and lifelong paralysis\n–Paralytic disease occurs in <1% of \ninfections (varies by serotype)\n–Non -paralytic clinical illness occurs in \n~25%, including 1% –5% with aseptic \nmeningitis\n–Approximately 75% of infections are \nasymptomaticPublic Health Problem\n\n▪Three poliovirus serotypes: type 1, type 2, and type 3\n▪Immunity to one serotype does not result in significant \nimmunity to other serotypes\n▪Ratio of paralytic cases to infections varies by serotype\n–Type 1: approximately 1/190\n–Type 2: approximately 1/1900\n–Type 3: approximately 1/1100Poliovirus Serotypes\nNathanson N, Kew OM. Am J Epidemiol 2010;172:1213 –29.\n\n▪Person -to-person spread of poliovirus occurs via the fecal -oral or oral-oral routes\n–Fecal -oral is the most important transmission pathway in settings with suboptimal \nhygiene and sanitation\n▪Patients are most infectious during days immediately before and after onset of \nsymptoms, but virus may remain present in stool for up to 6 weeks , sometimes \nlonger\n–Individuals with minor symptoms or no illness can shed virusPoliovirus is highly infectious\n▪Only polio vaccine used in the US\n▪Contains inactivated polioviruses types 1, 2, and 3 polioviruses\n▪Induces effective humoral immunity → prevents paralysis\n▪Induces some nasopharyngeal mucosal immunity, butlimited \nintestinal immunityInactivated Polio Vaccine (IPV)\n\n▪Live attenuated vaccine (Sabin)\n–Trivalent OPV ( tOPV ): contains types 1, 2, and 3\n–Bivalent OPV ( bOPV ): contains types 1 and 3\n–Monovalent OPV ( mOPV #): contains single type (#=1, 2, or 3)\n▪Replicates in gut, is shed in stool\n▪Induces humoral and mucosal immunity\n–Prevents paralysis and transmission ofpoliovirus\n▪Historical vaccine of choice for countries with outbreaks\n▪Attenuated virus can revert to a neurovirulent form \nthat causes paralysisOral Polio Vaccine (OPV)\n\n▪Novel, next -generation version of monovalent type 2 oral polio vaccine (nOPV2)\n▪Designed to be more genetically stable, less likely to revert to neurovirulent form\n▪March 2021 –December 2023:\n–Almost 1 billion doses administered in 35 countries under WHO Emergency Use \nListing (EUL) approval\n▪December 2023: Earned WHO prequalificationNovel Type 2 Oral Polio Vaccine (nOPV2)\nParalytic polio decreased rapidly in the US after \nintroduction of polio vaccine\n0500010000150002000025000\n1950\n1952\n1954\n1956\n1958\n1960\n1962\n1964\n1966\n1968\n1970\n1972\n1974\n1976\n1978\n1980\n1982\n1984\n1986\n1988\n1990\n1992\n1994\n1996\n1998\n2000\n2002\n2004\n2006\n2008\n2010\n2012\n2014\n2016\n2018\n20201994: Americas \ncertified polio -free\nYearNumber of poliomyelitis cases1955: Salk IPV\n1961: Sabin OPV1979: Last indigenous \nwild-type case in US\n2000: IPV only1997 : Sequential enhanced -potency\n          IPV followed by OPV\nGlobal Paralytic WPV1 and cVDPV  Cases1, Previous 12 Months2\nhttps://polioeradication.org/polio -today/polio -now/  \nWPV1 cases (latest onset)\nPakistan 5 24-Oct-23\nAfghanistan 6 04-Sep-23\ncVDPV1 cases (latest onset)\nDR Congo 90 24-Nov-23\nMozambique 3 06-Nov-23\nMadagascar 17 16-Sep-23\ncVDPV2 cases (latest onset)\nNiger 2 11-Dec-23\nIndonesia 3 06-Dec-23\nNigeria 80 03-Dec-23\nZimbabwe 1 02-Dec-23\nGuinea 46 28-Nov-23\nChad 49 26-Nov-23\nCôte d'Ivoire 6 22-Nov-23\nDR Congo 87 19-Nov-23\nYemen 4 17-Nov-23\nTanzania 3 16-Nov-23\nMali 12 06-Nov-23\nSouth Sudan 2 04-Nov-23\nMauritania 1 17-Oct-23\nCAR 10 07-Oct-23\nMozambique 1 28-Sep-23\nSomalia 4 16-Sep-23\nKenya 8 21-Aug-23\nBurundi 1 15-Jun-23\nBurkina Faso 2 04-Jun-23\nZambia 1 03-Apr-23\nBenin 2 15-Mar-23Data in WHO HQ as of 20 Feb. 20241Excludes viruses detected from environmental surveillance;   2Onset of paralysis: 21 Feb. 2023 to 20 Feb. 2024Endemic country (WPV1)\n\nParalytic Polio Case in New York State, July 2022\n•A case of paralytic polio caused by vaccine -derived poliovirus type 2 (VDPV2) was \nconfirmed in an unvaccinated young adult from  Rockland County, New York, on \nJuly 21, 2022\n•Genetic  sequencing has indicated a linkage to polioviruses collected in \nwastewater in Israel, United Kingdom, and Canada  \n•Rockland County has reported overall low vaccine coverage for over 20 years\n•In summer 2022, 60% of children under 2 years of age had received 3 doses of \nIPV (zip code level as low as 37%)\n•No additional paralytic cases were identified\nhttps://www.health.ny.gov/diseases/communicable/polio/docs/waste_water_surveillance_report.pdf   ▪Poliovirus type 2 genetically linked to the case detected \nin wastewater samples in New York (Rockland, Orange, \nSullivan, and Nassau counties and New York City)\n▪Retrospective testing detected poliovirus as early as \nApril 2022\n▪Only 2 positive samples since November 1, 2022 (most \nrecent February 22, 2023)\n▪No detections in samples collected in last 11+ months \n(since February 2023)Wastewater Testing for Poliovirus in New York\n\nhttps://www.health.ny.gov/diseases/communicable/polio/docs/waste_water_surveillance_report.pdf  \n▪2022 New York Strategy: Identify unvaccinated and undervaccinated persons, provide \ncatch -up vaccination with IPV\n▪WHO recommendations for poliovirus outbreaks in countries with exclusive IPV \nvaccination and high sanitation and hygiene:\n–Conduct a timely outbreak response with IPV only if poliovirus transmission is \nconfined in a well -defined population group or geographic area.\n–If transmission persists, consider an OPV response.\n▪Work Group asked to discuss considerations for potential use of nOPV2 as an \noutbreak response measure in the USOutbreak Response Vaccination\n▪Should nOPV2 be used in combination with a catch -up IPV campaign during a \nfuture type 2 poliovirus outbreak in the US?\n–Population: Persons living in area with circulating poliovirus\n–Intervention: nOPV2 vaccination for all + catch -up IPV vaccination for un - or under -vaccinated\n–Comparison: Catch -up IPV vaccination only\n–Outcomes: \n•Prevention of paralytic poliomyelitis\n•Extent and duration of poliovirus circulation in the community\n•Serious adverse effects, including vaccine -associated paralytic polio\n•Possible introduction of new vaccine -derived poliovirus type 2Theoretical Policy Question for Work Group\n▪Problem\n–Is the problem of public health importance?\n▪Benefits & Harms\n–How substantial are the desirable anticipated effects?\n–How substantial are the undesirable anticipated effects?\n–Do the desirable effects outweigh the undesirable effects?\n–What is the overall certainty of this evidence for the critical outcomes?\n▪Values\n–Does the target population feel that the desirable effects are large relative to the undesirable effects?\n–Is there important uncertainty about or variability in how much people value the main outcome?\n▪Acceptability\n–Is the intervention acceptable to key stakeholders?\n▪Resource Use\n–Is the intervention a reasonable and efficient allocation of resources?\n▪Equity\n–What would be the impact on health equity?\n▪Feasibility\n–Is the intervention feasible to implement?ACIP Evidence to Recommendations ( EtR) Framework\nWork group interpretation\nIs paralytic poliomyelitis a problem of public health importance?EtR Domain: Public Health Problem\nNoProbably \nnoProbably \nyesYes VariesDon’t \nknow\n▪Seroconversion among infants who had received 1 dose of IPV (Sáez -Llorens et al)\n–86% 28 days after 1 dose\n–98% 28 days after 2 doses\n▪Seroconversion among vaccine -naïve infants (Zaman et al; Wilkinson et al)\n–46% –64% 28 days after 1 dose\n–86% –90% 28 days after 2 dosesEffectiveness:\nHigh Rates of Seroconversion Following nOPV2\nSáez -Llorens et al. Lancet 2021;397:27 –38.\nZaman et al. Lancet 2023;401:131 –39.\nWilkinson et al. Lancet Infect Dis 2023;23:1062 –71.\n▪Sabin OPV2 reduces odds of fecal shedding of type 2 virus after a challenge ( Hird  and \nGrassly ) \n▪In small Phase 1 study among adults previously vaccinated with IPV ( Brickley  et al)\n•33% had detectable stool neutralization titer against PV2 at 28 days after 1 dose of nOPV2\n•15% had detectable PV2 -specific IgA in stool at 28 days after 1 dose of nOPV2Effectiveness: Mucosal Immunity\nHird  and Grassly . PLoS  Pathogens 2012;8(4):e1002599. \nBrickley  et al. J Infect Dis 2022;26:287 –91.\nFecal Shedding of nOPV2 Virus After 1st Dose of nOPV2\n% of Infants* with Detectable nOPV2 Virus in Stool\nDays after 1st dose of nOPV2 Measured by PCR Measured by Culture\n7 days 85% 40%\n14 days 52% 17%\n28 days 40% - 57% 1% - 14%\nZaman et al. Lancet 2023;401:131 –39.\nGast et al. J Infect Dis 2022;226:852 –61.*Includes newborn vaccine -naïve infants and infants who had previously received 3 bOPV  doses and 1 IPV dose\n▪nOPV2 more genetically stable than Sabin OPV2, less likely to regain neurovirulence\n▪Risk of VAPP in recipients\n–nOPV2: estimated 0.07 cases per million recipients (1 per 14.3M recipients)\n–Sabin OPV: 0.25 –4 cases per million recipients (1 per 0.25M –4M recipients)\n–Risk highest in unimmunized children receiving 1st dose of OPV or in \nimmunocompromised persons\n–Could be mitigated by limiting nOPV2 administration to persons who had \npreviously received ≥1 IPV doseRisk of Vaccine -Associated Paralytic Polio (VAPP) Following \nnOPV2\nBandyopadhyay and Zipursky. Lancet ID 2023;23:e67 –71.\n▪>700 million nOPV2 doses administered worldwide in 32 countries since March 2021\n–At least  7 separate emergences of new cVDPV2 linked to nOPV2 (cVPDV2 -n)\n–At least 61 detected paralytic cases associated with cVDPV2 -n\n▪Estimates: nOPV2 is 80% less likely than mOPV2 to seed new cVDPV2\n▪Risk of new cVDPV  is highest when campaign coverage is low in a population with \nlow immunity against poliovirusesRisk of Introducing a New Circulating Vaccine -Derived \nPoliovirus ( cVDPV ) Following nOPV2\nDavlantes et al. MMWR 2023;72(38):1041 –1042.\nhttps://polioeradication.org/wp -content/uploads/2024/01/GPEI -nOPV2 -Factsheet -20240105.pdf\n▪Most recipients will already be fully vaccinated with 3 –4 doses of IPV, already \nprotected against paralytic disease\n▪Anticipated benefits of nOPV2 to recipient\n–Higher anti -poliovirus type 2 antibody titer\n–Increased odds of mucosal immunity to poliovirus type 2\n–For undervaccinated persons: additional protection against paralytic disease\n–For previously vaccinated persons: unlikely clinical benefit\n▪Potential harms of nOPV2 to recipient\n–Extremely low, but non -zero risk of VAPP (<1 case per 14.3 million doses administered)\n–Risk of chronic infection if given to child with unrecognized immunocompromiseFor Individual nOPV2 Recipients\nPotential effects of adding nOPV2 to the IPV outbreak response\n▪Potential benefits to population\n–Decreased transmission among nOPV2 recipients → outbreak ends earlier → fewer paralytic cases\n–Passive vaccination of unvaccinated → decreased transmission and fewer paralytic cases\n▪Potential harms to population\n–Passive vaccination of unvaccinated → risk of VAPP among unvaccinated\n–Possible ongoing transmission of nOPV2 virus → new cVDPV2 -n\n–Possible chronic infection in immunocompromised\n▪Magnitude of benefits and harms depends on nOPV2 coverage, extent of mixing \nbetween nOPV2 recipients and unvaccinated (and immunocompromised)At the Population Level\nPotential effects of adding nOPV2 to the IPV outbreak response\nModeling: \nExpected Paralytic Cases Under Different Mixing Scenarios \nfor a cVDPV2 Outbreak Similar to 2022 New York Outbreak\nThompson et al. Vaccine 2024;42:819 –27.\nNote: Model assumed the number of vaccine doses administered was same as number of IPV doses administered \nduring 2022 New York outbreak.Modeled cVDPV2 cases\nVaccine used for outbreak response IPV None mOPV2 nOPV2 best nOPV2 worst\nSubpopulation isolation 0.88 1.89 0.64 0.55 0.67\nNo isolation 0.64 0.86 0.51 0.44 0.53\nPartial isolation 0.35 0.39 0.30 0.27 0.31\nModeling: \nExpected Paralytic Cases Under Different Mixing Scenarios \nfor cVDPV1 Outbreak and Hypothetical Novel Type 1 OPV\nThompson et al. Vaccine 2024;42:819 –27.\nModeled cVDPV1 cases\nVaccine used for outbreak response IPV None mOPV1 nOPV1 best nOPV1 worst\nSubpopulation isolation 56 65 45 22 47\nNo isolation 130 179 91 26 97\nPartial isolation 36 163 23 11 25\nNote: Model assumed the number of vaccine doses administered was same as number of IPV doses administered \nduring 2022 New York outbreak.\nMinimal Small Moderate Large VariesDon’t \nknowEtR Domain: Benefits & Harms\nWork group interpretation\nHow substantial are the desirable  anticipated effects of nOPV2* on the \nindividual and population levels?\n*during a VDPV2 outbreak, when nOPV2 given in addition to any IPV doses received as part of routine immunization \nMinimal Small Moderate Large VariesDon’t \nknowEtR Domain: Benefits & Harms\nWork group interpretation\nHow substantial are the undesirable  anticipated effects of nOPV2* on \nthe individual and population levels?\n*during a VDPV2 outbreak, when nOPV2 given in addition to any IPV doses received as part of routine immunization \nYes, favors \nnOPV2No, favors IPV \nonlyFavors either \noption equallyVaries Don’t knowEtR Domain: Benefits & Harms\nWork group interpretation\nDo the desirable effects of nOPV2* outweigh the undesirable effects on \nthe individual and population levels?\n*during a VDPV2 outbreak, when nOPV2 given in addition to any IPV doses received as part of routine immunization \n▪Expanded access investigational new drug application (EA -IND)\n▪Requires application to FDA and FDA authorization\n▪If implemented, nOPV2 EA -IND program must include\n–Signed informed consent by vaccinees and/or guardians\n–System for monitoring vaccine safety\n–Enhanced surveillance for possible VAPP cases\n–Environmental surveillance for new cVDPV2s\n–System for tracking and accounting for every dose for containment purposesImplementing an nOPV2 Program in the US\nNoProbably \nnoProbably \nyesYes VariesDon’t \nknowEtR Domain: Resource Use\nWork group interpretation\nIs an nOPV2 campaign* a reasonable and efficient allocation of \nresources?\n*during a VDPV2 outbreak, when nOPV2 given in addition to any IPV doses received as part of routine immunization \nNoProbably \nnoProbably \nyesYes VariesDon’t \nknowEtR Domain: Feasibility\nWork group interpretation\nIs a nOPV2 campaign* feasible to implement?\n*during a VDPV2 outbreak, when nOPV2 given in addition to any IPV doses received as part of routine immunization \n▪Trivalent OPV ( tOPV ) was removed from vaccination schedule in 2000 and replaced with IPV because \nany risk of VAPP was deemed unacceptable; this might be barrier to acceptance of a new OPV vaccine\n▪The need for signed informed consent will likely be a deterrent\n▪Unclear whether general public will accept an OPV if they are already protected from paralytic \ninfection by IPV\n▪Unclear whether population most at risk (those with low childhood vaccination coverage and high \nrates of vaccine skepticism) will accept an OPV vaccine\n▪Perceptions of risk and vaccine acceptance might shift in outbreak setting, if there is >1 paralytic case \nin a communityValues and Acceptability Considerations\nNoProbably \nnoProbably \nyesYes VariesDon’t \nknowEtR Domain: Values of Target Population \nWork group interpretation\nDoes the target population feel that the desirable effects of nOPV2* are \nlarge relative to undesirable effects?\n*during a VDPV2 outbreak, when nOPV2 given in addition to any IPV doses received as part of routine immunization \nImportant \nuncertainty \nor variabilityProbably \nimportant \nuncertainty \nor variabilityProbably not \nimportant \nuncertainty \nor variabilityNo \nimportant \nuncertainty \nor variabilityNo known \nundesirable \noutcomesEtR Domain: Values of Target Population \nWork group interpretation\nIs there important uncertainty or variability in how much people value \nthe main outcomes?\nNoProbably \nnoProbably \nyesYes VariesDon’t \nknowEtR Domain: Acceptability to Key Stakeholders\nWork group interpretation\nIs nOPV2* acceptable to key stakeholders?\n*during a VDPV2 outbreak, when nOPV2 given in addition to any IPV doses received as part of routine immunization \nGlobally\n▪Single manufacturer ( BioFarma , Indonesia)\n▪Managed via a global stockpile\n▪Supply shortages have occurred in the past\n▪In US, IPV is readily available, provides protection against paralysis from cVDPV2\n▪In many countries with cVDPV2 outbreaks, limited protection against cVDPV2 unless \nthere are nOPV2 or mOPV2 campaigns\nIn US\n▪Preventing transmission protects unvaccinated/undervaccinated and \nimmunocompromisedEquity Considerations\nReduced \nequityProbably \nreduced\nequityProbably \nno impactProbably \nincreased \nequityIncreased \nequityVariesDon’t \nknowEtR Domain: Equity\nWork group interpretation\nWhat would be the impact of an nOPV2 campaign* in the US on health \nequity?\n*during a VDPV2 outbreak, when nOPV2 given in addition to any IPV doses received as part of routine immunization \nUndesirable  \nconsequences \nclearly  \noutweigh \ndesirable \nconsequences \nin most settingsUndesirable \nconsequences \nprobably \noutweigh \ndesirable \nconsequences \nin most \nsettingsThe balance \nbetween \ndesirable and \nundesirable \nconsequences \nis closely \nbalanced or \nuncertainDesirable  \nconsequences \nprobably  \noutweigh \nundesirable \nconsequences \nin most settingsDesirable  \nconsequences \nclearly  \noutweigh \nundesirable \nconsequences \nin most settingsThere is \ninsufficient \nevidence to \ndetermine the \nbalance of \nconsequencesWork Group Judgement: Balance of Consequences\nUsing nOPV2 as an outbreak control measure in the US*\n*during a VDPV2 outbreak, when nOPV2 given in addition to any IPV doses received as part of routine immunization \n▪At this time, the work group believes the undesirable consequences probably \noutweigh OR are closely balanced with the desirable consequences.\n▪Main considerations included\n–IPV is readily available in the US and protects against paralytic disease\n–Primary benefit of adding nOPV2 to an outbreak response would be to reduce transmission of outbreak virus, \nreduce risk of paralytic disease in undervaccinated or immunocompromised persons\n–Differences of opinion regarding the value of reducing asymptomatic  transmission or ending asymptomatic  \ntransmission earlier during outbreak\n–Extremely low, but non -zero risk of VAPP (est. 1 per 14.3 million recipients) or new cVDPV2\n–Uncertainty about public and stakeholder acceptance of nOPV2\n▪Balance of undesirable consequences vs. desirable consequences might shift in the \nfuture depending on size and scope of outbreakSummary\nUse of nOPV2 During a cVDPV2 Outbreak in the US\nQuestions and Discussion", "summary": "Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-28-29-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-02-28-29/02-POLIO-Kidd-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 41}
{"title": "Pneumococcal 06 Kobayashi 508", "content": "Pneumococcal Vaccines Work Group Considerations and \nNext Steps \nMiwako Kobayashi, MD, MPH \nPneumococcal Vaccines Work Group \nAdvisory Committee on Immunization Practices \nFebruary 22, 2023 \n  \n         \n        \n      \n         \n         \n         Proposed Policy Questions \n Should PCV20 be recommended as an option for pneumococcal \nconjugate vaccination according to currently recommended dosing and schedules, for U.S. children aged <2 years? \n Should PCV20 without PPSV23 be recommended as an option for pneumococcal vaccination for U.S. children aged 2–18 years with underlying medical conditions that increase the risk of pneumococcal disease? \n \n      \n           \n      \n          \n       Additional Considerations \n Cost-effectiveness analysis will be performed to assess: \n• Incremental benefit of PPSV23 use in addition to PCV20 in children \naged 2–18 years with underlying medical conditions. \n• Incremental benefit of PCV20 use in children who completed the \nrecommended PCV series with either PCV13 or PCV15. \nPneumococcal  Disease  Risk in Children  with  Underlying  Medical  \nConditions \nAsthma,  Chronic  Kidney  Disease,  Chronic  Liver  Disease \n       \n Are childre  n wit  h chroni  c kidne  y disease o  f an  y stag  e a t increase  d risk  \no f pneumococca  l disease? Specific Questions Being Considered by the Work \nGroup \n• \n•\n•  Are  children  with  chroni  c live  r diseas  e a t increase  d risk  o f pneumococcal  \ndisease? Are  children  with  asthma  at  increased  risk  of  pneumococcal  disease  \nregardless  o f high-dose  oral  corticosteroid  use?  \n        \n \n       \n \n \n     \n  \n    \n       \n    \n       Differences in the Indications for Children vs Adults \nwith Asthma \n• Pediatric recommendation1,2: \n• Including asthma if treated with high-dose oral \ncorticosteroid therapy \n• Adult recommendation3,4: \n• Includes chronic obstructive pulmonary disease, \nemphysema, and asthma \n1. Nuorti et al. MMWR RR 2010 \n2. Kobayashi et al. MMWR 2022. 71(37); 1174–1181 \n3. Matanock et al. MMWR 2019 \n4. Kobayashi et al. MMWR 2022. 71(4); 109–117 \nRisk-Based Pneumococcal Vaccine Recommendations    \n  \n    \n \n \n  \n \n     \n      \n   \n     \n    \n \n     \n            \n  Diabetes mellitus \nCerebrospinal fluid leak Cochlear implant Chronic renal failure or nephrotic syndrome Congenital or acquired asplenia, or splenic \ndysfunction \nCongenital or acquired immunodeficiency \nDiseases and conditions treated with \nimmunosuppressive drugs or radiation therapy \nHIV infection \nSickle cell disease or other hemoglobinopathies \nSolid organ transplant \nShould we add “chronic liver disease” as part of pediatric \nrisk-based recommendation? Children Adults \nAlcoholism \nC\nhronic heart disease \nCh\nronic lung disease \nChronic liver disease \nCigarette smoking \nRisk-Based Pneumococcal Vaccine Recommendations \nChildren Adults \nAlcoholism \nChronic heart disease \nChronic lung disease Chronic liver disease Cigarette smoking    \n      \n \n \n  \n \n     \n      \n   \n     \n    \n \n     \n           \n        \n       \n    Diabetes mellitus \nCerebrospinal fluid leak Cochlear implant \nor nephrotic syndrome\nChronic renal failure \nCongenital or acquired asplenia, or splenic \ndysfunction \nCongenital or acquired immunodeficiency \nDiseases and conditions treated with \nimmunosuppressive drugs or radiation therapy \nHIV infection \nSickle cell disease or other hemoglobinopathies \nSolid organ transplant The intent has been to provide additional protection for \nthose on dialysis or about to be on dialysis \n Should the risk-based recommendations be expanded to \nall CKD stages? \nWork  Group  Next  Steps \n   \n          \n    \n        \n             Work Group Next Steps \n• Review of evidence and Work Group interpretation of remaining EtR domains \n(Values, Acceptability, Resource Use, Feasibility ) \n• Review findings from cost-effectiveness analyses (CDC and other groups) \n• Draft policy options on PCV20 use in U.S. children for consideration by the committee \n   \n         \n    \n           \n       Questions for the Committee \n• Does the Committee agree with the policy questions being \nconsidered by the Work Group? \n• Are there additional data the Committee would like to see before deciding on policy options for a vote? \n    \n \n      \n                  \n         For more information, contact CDC \n1-800-CDC-INFO (232-4636) TTY: 1-888-232-6348 www.cdc.gov \nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.", "summary": "Pneumococcal Vaccines Work Group Considerations and  Next Steps  Miwako Kobayashi, MD, MPH  Pneumococcal Vaccines Work Group  Advisory Committee on Immunization Practices  February 22, 2023                                                            Proposed Policy Questions   Should PCV20 be recommended as an option for pneumococcal  conjugate vaccination according to currently recommended dosing and schedules, for U.S. children aged <2 years?   Should PCV20 without PPSV23 be recommended as…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/Pneumococcal-06-Kobayashi-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 12}
{"title": "Mening 01 Poehling 508", "content": "National Center for Immunization & Respiratory Diseases \nACIP Meningococcal Vaccines Work Group \nIntroduction \nKatherine Poehling, MD, MPH \nWork Group Chair \nFebruary 23, 2023 \n   \n \n  \n \n \n  \n  \n \n  \n \n  \n  \n   \n  \n \n \n  \n \n    \n \n  \n  \n  \n  \n  \n  \n   \n  \n  \n   \n  \n  Meningococcal Vaccines Work Group \n ACIP Members \n– Kat\nherine Poehling (Chair) \n– Lynn Bahta \n– Jam\nie Loehr \n Ex Officio Members \n– Mar\ngaret Bash (FDA) \n– Mark Connelly (FDA) \n– Fra\nncisco Leyva (NIH) \n CDC Lead \n– Sam Crowe (DBD/NCIRD) \n Liaisons and Consultants \n– A\nmra Resic (AAFP) \n– Samir Shah (AAP) \n– Sharon McMullen (ACHA) \n– Cacky Tate (AIM) \n– Paul Cieslak (CSTE) \n– Jeff Goad (NFID) \n– Jessica Cataldi (PIDS) \n– Amy Middleman (SAHM) – David Stephens (Emory) \n CDC Contributors \n– L\neAnne Fox (DBD/NCIRD) \n– Susan Hariri (DBD/NCIRD) \n– Lucy McNamara (DBD/NCIRD) \n– Alison Albert (DBD/NCIRD) \n– Noele Nelson (DBD/NCIRD) \n– Jonathan Duffy (DHQP/NCEZID) \n– Tanya Myers (DHQP/NCEZID) \n– Ismael Ortega-Sanchez (DVD/NCIRD) \n– Liz Velazquez (ISD/NCIRD) \n– Jessica MacNeil (ACIP Secretariat) \n GRADE/EtR \n– D\noug Campos-Outcalt (Arizona) \n– Rebecca Morgan (McMaster) \n2 \n   \n  \n      \n   \n \n October ACIP Meeting Recap \n Menveo one-vial presentation \n\n Introduction to the two new MenABCWY vaccines \n–\n Manufacturers: GSK and Pfizer \n– Policy questions \n– PICOs \n– Next steps \n3 \n   \n       \n    Work Group Schedule Updates \nTask 2022 2023 2024 \n6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 \nMenveo Solution \nPfizer Pentavalent Vaccine \nGSK Pentavalent Vaccine \n4 \n    \n        \n  \n \n   \n   \n     \n  \n  Proposed Timeline of ACIP Presentations \nFebruary \n2023 June \n2023 October \n2023 \n• Epidemiology of • Pfizer GRADE, EtR, • Pfizer vote \nmeningococcal and cost study \n• GS\nK GRADE, EtR, di\nsease \n• GS\nK trial data and cost study \n• Pf\nizer trial data \n5 \n     \n           \n  \n        \n          \n    \n     \n      Summary of Recent Work Group Activities \n GSK and Pfizer presented on their pentavalent vaccines and work group \nasked clarifying questions \n Work group discussed whether to reconsider adolescent immunization schedule \n Decided to postpone any reviews of the schedule until after both pentavalent vaccines have been assessed \n– Vaccine reviews will be complex and challenging \n– Need to understand epidemiology of meningococcal disease after COVID-19 \n6 \n  \n      \n  \n    \n \n        \n  Agenda for Today \n Epidemiology of Meningococcal Disease in the United States \n–\n A\nmy Rubis, CDC \n\n Pfizer’s MenABCWY Vaccine Clinical Trials Data \n–\n P\nfizer Representative \n\n Work Group Interpretation of Pfizer’s MenABCWY Vaccine Clinical Trials Data \n–\n Sam Crowe, CDC \n7 \n    \n \n      \n                        \n   For more information, contact CDC \n1-800-CDC-INFO (232-4636) TTY: 1-888-232-6348 www.cdc.gov \nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.", "summary": "National Center for Immunization & Respiratory Diseases  ACIP Meningococcal Vaccines Work Group  Introduction  Katherine Poehling, MD, MPH  Work Group Chair  February 23, 2023                                                                                              Meningococcal Vaccines Work Group   ACIP Members  – Kat herine Poehling (Chair)  – Lynn Bahta  – Jam ie Loehr   Ex Officio Members  – Mar garet Bash (FDA)  – Mark Connelly (FDA)  – Fra ncisco Leyva (NIH)   CDC Lead  – Sam…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/Mening-01-Poehling-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 8}
{"title": "Mening 02 Rubis 508", "content": "National Center for Immunization & Respiratory Diseases \nEpidemiology of Meningococcal Disease in the \nUnited States \nAmy Rubis, MPH \nAdvisory Committee on Immunization Practices Meeting \nFebruary 23, 2023 \n       \n \n  \n    \n  Agenda \n Overall epidemiology of meningococcal disease in the \nUnited States \n Recent notable epidemiology \n– C\niprofloxacin- and penicillin-resistant serogroup Y \nmeningococcal disease cases \n– Outbreaks \n2 \n  \n      \n  \n   \n \n Meningococcal Disease Surveillance \n Cases reported through National Notifiable Diseases \nSurveillance System (NNDSS) \n\n Additional serogroup, outcome, and clinical characteristics collected nationally through Enhanced Meningococcal Disease Surveillance (EMDS) \n–\n Isolates submitted for whole genome sequencing \n3 \n    \n  \n         \n \n      \n      \n         \n   Meningococcal Disease Surveillance Data, 2020–2022 \n 2020 data are final \n Delays in obtaining and finalizing surveillance data for 20\n21 \nan\nd 20\n22 \n– Ser\nogroup missing for 17% of cases \n– Clinical characteristics not yet complete for 20\n22 \n– Al\nl available isolates not yet received and tested to confirm \nserogroup and antimicrobial susceptibility \n4 \n   \n  \n                   \n     \n     \n Meningococcal Disease Incidence – \nUnited States, 1996–2019 1.2 cases/100,000 \npopulation Incidence per 100,000 1.40 \n1.20 \n1.00 0.80 0.60 \n0.40 \n0.20 \n0.11 cases/100,000 \npopulation MenACWY vaccine \nMenB vaccine \n0.00 \n1996 2000 2005 2010 2015 2019 \nYear \nAbbreviations: MenACWY vaccine = quadrivalent conjugate meningococcal vaccine against serogroups A, C, W, Y; MenB vaccine = serogroup B meningococcal vaccine \nSource: 1996–2019 NNDSS Data \n5 \n   \n    \n                   \n             \n Meningococcal Disease Incidence – \nUnited States, 1996–2021* 1.2 cases/100,000 \npopulation Incidence per 100,000 1.40 \n1.20 \n1.00 0.80 0.60 \n0.40 \n0.20 \n0.06 cases/100,000 \npopulation MenACWY vaccine \nMenB vaccine \n0.00 \n1996 2000 2005 2010 2015 2021 \nYear \nAbbreviations: MenACWY vaccine = quadrivalent conjugate meningococcal vaccine against serogroups A, C, W, Y; MenB vaccine = serogroup B meningococcal vaccine \nSource: 1996–2021 NNDSS Data. *2021 NNDSS data are preliminary. 6 \n   \n    \n                   \n             \n Meningococcal Disease Incidence – \nUnited States, 1996–2022* 1.2 cases/100,000 \npopulation Incidence per 100,000 1.40 \n1.20 \n1.00 0.80 0.60 \n0.40 \n0.20 \n0.09 cases/100,000 \npopulation MenACWY vaccine \nMenB vaccine \n0.00 \n1996 2000 2005 2010 2015 2020 2022 \nYear \nAbbreviations: MenACWY vaccine = quadrivalent conjugate meningococcal vaccine against serogroups A, C, W, Y; MenB vaccine = serogroup B meningococcal vaccine \nSource: 1996–2022 NNDSS Data. *2021–2022 NNDSS data are preliminary. 7 \n      \n     \n                \n     Trends in Meningococcal Disease Incidence by \nSerogroup – United States, 2006–2022* Incidence per 100,000 0.12 \nB C Y W Other \n0.1 \n0.08 \n0.06 \n0.04 \n0.02 \n0 \n2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 \nYear \nSource: NNDSS data with additional serogroup data from Active Bacterial Core surveillance (ABCs) and state health departments \n*2021 and 2022 data are preliminary \n8 \n      \n    \n                  \n 0 0.2 0.4 0.6 0.8 1 1.2 1.4 Incidence per 100,000 B ACWY Oth/Unk Average Annual Meningococcal Disease Incidence by \nAge-Group and Serogroup―United States, 2010–2019 \n<1 year 1 year 2-4 years 5-10 11-15 16-20 21-25 26-44 45-64 65-84 85+ \nyears years years years years years years years \nA\nge Group \nSource: NNDSS data with additional serogroup data from ABCs and state health departments \n 9 \nAverage Annual Meningococcal Disease Incidence by \nAge-Group and Serogroup―United States, 2020–2022* \n1.4 \nB ACWY Oth/Unk \n1.2 \n1 \n0.8 \n0.6 0.4 0.2 \n0 \n<1 year 1 year 2-4 5-10 11-15 16-20 21-25 26-44 45-64 65-84 85+ \nyears years years years years years years years years       \n    \n             \n         \n Age Group \nSource: NNDSS data with additional serogroup data from ABCs and state health departments \n*2021 and 2022 data are preliminary \nIncidence per 100,000 \n10 \n   \n      \n     \n  \n   \n     \n       \n      \n    Recent Meningococcal Disease Cases \n Historically resistance in N. meningitidis was rare \n Ciprofloxacin- and penicillin-resistant serogroup Y cases \ndetected in 2020 \n– 27 cases from 2019–2022 \n– 7\n8% among Hispanic or Latino persons \n– Age range <1–97 years, mean 31, median 23 \n• Only 1 case 11–20 years of age \n– No cases in vaccinated individuals \n11 \n    \n        \n  \n         \n  \nResistant Serogroup Y Meningococcal Disease \nCases―United States, 2013–2022 \nData are not final and \n0 0.02 0.04 0.06 0.08 0.1 0.12 0.14 0.16 0.18 0.2 \n0 5 10 15 20 25 \nIncidence per 100,000 Number of cases numbers may increase \n2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 \nβ-lactamase-positive only Dual-resistant Meningococcal Disease Incidence \n*2021 and 2022 data are preliminary 12 \n   \n         \n     \n \n       \n     \n       \n       \n       Recent Meningococcal Disease Outbreaks \n Largest outbreak predominantly in men who have sex with \nmen (MSM) reported to date \n– January 2022–present* \n– 4\n3 serogroup C cases, 9 deaths (21% CFR) \n– 12/43 non-MSM (5 women) in outbreak \n– 15 (35%) cases in people living with HIV \n– Age range 20–77 years, mean 35, median 31 \n13 \n*The outbreak is ongoing. Case counts may change.  \n   \n      \n \n     \n       \n       \n     \n       Recent Meningococcal Disease Outbreaks \n Unusually lethal strain of serogroup Y \n– June 2022–present* \n– 11 cases, 3 deaths (27% CFR) \n–\n 10/11 cases in Black or African American persons \n– Age range 30–78 years, mean 46, median 39 \n– Sequence type 1466, clonal complex 174 \n14 \n*The outbreak is ongoing. Case counts may change.  \n   \n  \n      \n   \n          \n    Recent Meningococcal Disease Outbreaks \n People experiencing homelessness \n– 2021 \n• 1 out\nbreak of 3 serogroup C cases \n• Age \nrange 22–37 years \n– 2022 \n• 1 ou\ntbreak of 2 serogroup C cases at the same shelter \n• Ag\nes: 37 and 41 years \n15 \n      \n    \n     \n      \n       \n       \n        Conclusions \n Incidence of meningococcal disease declined during 2020– \n2021, but increased in 2022 \n New strains emerging in the US \n– Pr\nedominantly affecting racial and ethnic minority groups \n– Unclear how this will change overall epidemiology \n More complete 2021 and 2022 data are needed \n More years of data needed to understand post-COVID-19 \nep\nidemiology \n16 \n    \n \n      \n                        \n    Thank You \nFor more information, contact CDC \n1-800-CDC-INFO (232-4636) TTY: 1-888-232-6348 www.cdc.gov \nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.", "summary": "National Center for Immunization & Respiratory Diseases  Epidemiology of Meningococcal Disease in the  United States  Amy Rubis, MPH  Advisory Committee on Immunization Practices Meeting  February 23, 2023                      Agenda   Overall epidemiology of meningococcal disease in the  United States   Recent notable epidemiology  – C iprofloxacin- and penicillin-resistant serogroup Y  meningococcal disease cases  – Outbreaks  2                      Meningococcal Disease Surveillance  …", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/Mening-02-Rubis-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 17}
{"title": "Mening 03 Maguire 508", "content": "1 Pfizer ConfidentialMenABCWY \nMeningococcal  Vaccine\nJason D. Maguire, MD, MPH\nClinical Lead, Phase 3 Program \nPfizer Vaccines Clinical R&D\n2 Pfizer Confidential\nFor Internal and Restricted Pfizer Use Only –Not for Distribution. Privileged and Confidential.MenABCWY vaccine composition\nConfidential•MenABCWY vaccine is composed of drug substance from:\n–Trumenba®(MenB-fHbp): licensed in the US for the prevention of invasive disease caused by Neisseria meningitidis group \nB in individuals 10 through 25 years of age\n–Nimenrix® (MenACWY- TT): licensed ex -US for the prevention of invasive disease caused by Neisseria meningitidis \nserogroups A, C, W, and Y in individuals 6 weeks of age and older. •Active immunization of individuals 10 through 25 years of age against invasive meningococcal diseases \ncaused by Neisseria meningitidis serogroups A, B, C, W, Y\n•Dosing:\n–Administer two doses at least 6 months apart for prevention of meningococcal disease caused by serogroups A, B, C, W \nand Y . \n–Administer one dose for prevention of meningococcal disease caused by serogroups A, C, W and Y . \n–A booster dose may be administered to individuals who have previously completed a primary series with MenABCWY or \nMenB-fHbp vaccine or who have previously received MenACWY conjugated vaccinesIndication and dosing being sought for MenABCWY vaccineMenABCWY Vaccine Overview\n3 Pfizer ConfidentialAdolescent meningococcal vaccination platform options for MenABCWY\nvaccine\n11-12 years 16-23 years\nB B ACWY ACWY\nABCWY ABCWY ABCWY\nABCWY ABCWY ABCWY\nStudy Population 10- 25 years (ACWY -naïve and primed)Current Vaccine \nRecommendation\nMenABCWY \nvaccine options\nMenABCWY \nvaccine clinical \ndata\n0, 6-12 monthsACWY \nprotectionABCWY \npr\notectionBooster dos e (4 years) \nfor ABCWY protection\n4 Pfizer ConfidentialMenABCWY vaccine clinical program overview\nBlood vial image source: Flaticon.com•ABCWY responses after 2 \ndoses (0,6m) \n•ACWY responses after 1 doseKey immunogenicity ( hSBA) data to \nbe discussed\n•ABCWY responses after 2 doses (0,12m)\n•ABCWY 4 -year persistence \nand booster response\n•All participants were meningococcal serogroup B vaccine naïve prior to study entry\n•80% of participants in the Phase 3 study were Caucasian; 10% black and African Americans; 25% of participants being Hispanic or Latino\n5 Pfizer Confidential Breakthroughs that change patients’ livesImmunogenicity\n6 Pfizer ConfidentialImmunogenicity objectives and endpoints\nAbbreviations: hSBA=human serum bactericidal assay; GMT=geometric mean titer ;MenB =serogroup B\n*For participants with a baseline hSBA titer <1:4, seroresponse is defined as a titer ≥1:16. For those with a baseline hSBA titer ≥1:4 and <1:8 (<1:16 for A22), seroresponse is a titer ≥4 times the 1:8 \n(1:16 for A22). For those with a baseline hSBA titer ≥1:8 (≥1:16 for A22), seroresponse is a titer ≥4 times the baseline titer. †hSBA titer ≥1:8 (1:16 for A22) for all 4 primary strains 1 month after Dose 2.MenB immunogenicity analysis: Same approach taken as for Trumenba licensure in the US\n•4 MenB test strains utilized, 2 from Factor H Binding Protein ( fHbp ) subfamily A (A22, A56) and 2 from subfamily B (B24, B44) \n•hSBA results provide information on breadth of coverage against MenB strains\n•All strains express vaccine -heterologous fHbp variants \n•Strains and fHbp variants expressed are representative of known genetic diversity; strains were randomly selected\n•hSBA seropositivity defined as titers ≥1:8 or ≥1:16, which is greater than the 1:4 correlate of protectionFDA agreement for licensure\nACWY evaluation\n(non-inferiority after 1 and 2 \ndoses of MenABCWY vaccine \nversus MenACWY -CRM)B ev aluation\n(non\n-inferiority after 2 doses of \nMenABCWY vaccine versus \nMenB -fHbp)A BCWY evaluation\n(O\nther endpoints)\n•h\nSBA seroresponse* (4 - fold)\n•Naïve and primed participants•hSBA seroresponse* (4 - fold) \n•Composite response†•hSBA thresholds (1:4, 1:8, 1:16) \n•G\nMTs\n7 Pfizer ConfidentialImmunogenicity\nACWY-naive\n8 Pfizer Confidential\nA single dose of MenABCWY vaccine can be used as an alternative to \nACWY vaccines in ACWY-naïve adolescentsStudy C3511001 | Evaluable Immunogenicity Population\nPercentage of participants achieving hSBA seroresponse*1 month after \nvaccination for serogroups \n0102030405060708090100\nA C W Y%ACWY \nAbbreviations: hSBA=serum bactericidal assay using human complement.\n*For participants with a baseline hSBA titer <1:4, seroresponse is defined as a titer ≥1:16. For those with a baseline hSBA titer ≥1:4 and <1:8, seroresponse is a titer ≥4 times the 1:8. For those with a baseline hSBA\ntiter ≥1:8, seroresponse is a titer ≥4 times the baseline titer.\nN=492- 501 for MenABCWY group; N=244- 254 for MenB -fHbp + MenACWY -CRM group.\nData on File, Study C3511001 (NCT04440163) Aug 2022, Pfizer Inc.MenABCWY MenB -fHbp + MenACWY -CRM\n•1 dose of MenABCWY vaccine was noninferior to 1 dose of MenACWY -CRM in ACWY -naïve participants\n•82.4% -99.4% of participants had serogroups ACWY hSBA titers ≥1:8 after 1 dose of MenABCWY vaccineComparisons (ACWY -naïve participants):\n•MenABCWY vaccine 1 month after first dose \n•MenACWY -CRM 1 month after single dose\n9 Pfizer Confidential0102030405060708090100\nA C W Y%Percentage of participants achieving hSBA seroresponse*1 month after \nvaccination for serogroups ACWY\nMenABCWY MenB -fHbp + MenACWY -CRM2 doses of MenABCWY vaccine elicit higher responses versus a single \ndose of MenACWY-CRM in ACWY -naïve participants\nAbbreviations: hSBA=serum bactericidal assay using human complement.\n*For participants with a baseline hSBA titer <1:4, seroresponse is defined as a titer ≥1:16. For those with a baseline hSBA titer ≥1:4 and <1:8, seroresponse is a titer ≥4 times the 1:8. For those with a baseline hSBA\ntiter ≥1:8, seroresponse is a titer ≥4 times the baseline titer.\nN=439- 451 or MenABCWY group; N=244- 254 for MenB -fHbp + MenACWY -CRM group.\nData on File, Study C3511001 (NCT04440163) Aug 2022, Pfizer Inc.Study C3511001 | Evaluable Immunogenicity Population\n•2 doses of MenABCWY vaccine were noninferior to 1 dose of MenACWY -CRM in ACWY -naïve participants\n•99.1-99.8% of participants had serogroups ACWY hSBA titers ≥1:8 after 2 doses of MenABCWY vaccine\nComparisons (ACWY -naïve participants):\n•MenABCWY vaccine 1 month after second dose \n•MenACWY -CRM 1 month after single dose\n10 Pfizer Confidential0102030405060708090100\nA22 A56 B24 B44 Composite%\nMenABCWY MenB -fHbp + MenACWY -CRMresponse†1 month after vaccination for serogroup B Percentage of participants achieving hSBA seroresponse*and composite Study C3511001 | Evaluable Immunogenicity Population\nAbbreviations: hSBA=serum bactericidal assay using human complement .\n*For participants with a baseline hSBA titer <1:4, seroresponse is defined as a titer ≥1:16. For those with a baseline hSBA titer ≥1:4 and <1:8 (<1:16 for A22), seroresponse is a titer ≥4 times the 1:8 (1:16 for A22). \nFor those with a baseline hSBA titer ≥1:8 (≥1:16 for A22), seroresponse is a titer ≥4 times the baseline titer. †hSBA titer ≥1:8 (≥1:16 for A22) for all 4 MenB strains 1 month after Dose 2. ^≥1:16 for A22 strain\nN=755- 845 for MenABCWY group; N=383- 419 for MenB -fHbp + MenACWY -CRM group.\nData on File, Study C3511001 (NCT04440163) Aug 2022, Pfizer Inc.•2 doses of MenABCWY vaccine were noninferior to 2 doses of MenB -fHbp\n•83.4-98.7% of participants had serogroup B hSBA titers ≥1:8^after 2 doses of MenABCWY vaccine2 doses of MenABCWY vaccine elicit higher responses versus 2 doses of \nMenB -fHbp in B-naïve participants\nComparisons  (B -naïve participants):\n•MenABCWY vaccine 1 month after second dose \n•MenB -fHbp 1 month after second dose\n\n11 Pfizer ConfidentialMenABCWY vaccine protects against all 5 serogroups with 2 doses given 6 \nto 12 months apart\nSeroresponse* 1m PD2MenABCWY 0, 6m\n(Study 1001)MenABCWY 0, 12m\n(Study 1004)\nSerogroups N^ % 95% CI N^ % 95% CI\nA 447 97.8 95.9, 98.9 116 99.1 95.3, 100\nC 451 93.3 90.6, 95.5 115 99.1 95.3, 100\nW 439 97.3 95.3, 98.6 113 99.1 95.2, 100\nY 446 94.4 91.8, 96.3 111 98.2 93.6, 99.8\nMenB strain\nA22 778 83.0 80.2, 85.6 111 95.5 89.8, 98.5\nA56 807 95.9 94.3, 97.2 115 100 96.8, 100\nB24 833 68.1 64.8, 71.2 113 92.9 86.5, 96.9\nB44 845 86.5 84.0, 88.7 116 94.8 89.1, 98.1\nMenB composite hSBA response†\nBefore Dose 1 812 1.2 0.6, 2.3 114 0.9 0.0, 4.8\n1 Month after Dose 2 755 78.3 75.2, 81.2 110 96.4 91.0, 99.0Study C3511001, Evaluable Immunogenicity Population │ Study C3511004, Evaluable Immunogenicity Population \nAbbreviations: hSBA=serum bactericidal assay using human complement; MenB =serogroup B.\n*For participants with a baseline hSBA titer <1:4, seroresponse is defined as a titer ≥1:16. For those with a baseline hSBA titer ≥1:4 and <1:8 (<1:16 for A22), seroresponse is a titer ≥4 times the 1:8 \n(1:16 for A22). For those with a baseline hSBA titer ≥1:8 (≥1:16 for A22), seroresponse is a titer ≥4 times the baseline titer.  ^ Number of subjects with valid and determinate hSBA titer for the given \nstrain; for study 1001, population includes ACWY -naïve participants for serogroups ACWY.†hSBA titer ≥ 1:8 (1:16 for A22) for all 4 MenB strains 1 month after Dose 2.\nData on File, Study C3511001 (NCT04440163) and C3511004 (NCT04440176) Aug 2022, Pfizer Inc.•2 doses of MenABCWY vaccine given 12 months apart elicit higher serogroup B responses\n•98.3-100% of participants had serogroups ABCWY hSBA titers ≥1:8 following 2 doses of MenABCWY\nvaccine given 12 months apart\n12 Pfizer ConfidentialMenACWY seroprotection persists up to 4 years in ACWY -naïve participantsStudy B1971057 | mITT and Booster Evaluable Immunogenicity Populations\nPercentage of individuals* with hSBA titers ≥ 1:8 at all timepoints\nA\nWC\nY020406080100\nBaseline 1m PD2 12m PD2 24m PD2 36m PD2 48m PD2Percentage (%)\n020406080100\nBaseline 1m PD2 12m PD2 24m PD2 36m PD2 48m PD2\n020406080100\nBaseline 1m PD2 12m PD2 24m PD2 36m PD2 48m PD2Percentage (%)020406080100\nBaseline 1m PD2 12m PD2 24m PD2 36m PD2 48m PD2Baseline           7m PD1         18m PD1       30m PD1         42m PD1        54m PD1      \nBaseline          7m PD1        18m PD1        30m PD1        42m PD1        54m PD1Baseline        7m PD1       18m PD1        30m PD1      42m PD1      54m PD1 \nBaseline         7m PD1       18m PD1       30m PD1       42m PD1       54m PD1 \nMenABCWY MenB -fHbp + MenACWY -CRM\nAbbreviations: hSBA=serum bactericidal assay using human complement; PB=post booster; PD1=post dose 1; PD2=post dose 2.\n*Number of subjects with valid and determinate hSBA titer for the given strain ranged from 95- 112 for MenABCWY and 54- 64 for MenB -fHbp + MenACWY -CRM (Stage 2 mITT population [baseline through \n36m PD2/42m PD1]), and 59- 60 for MenABCWY and 36- 37 for MenB -fHbp + MenACWY -CRM (Booster evaluable immunogenicity population [48m PD2 /54m PD1 Post Primary and Post Booster]).\nData on File, Study B1971057 (NCT03135834) Aug 2022, Pfizer Inc.\n13 Pfizer ConfidentialStudy B1971057 | Booster Evaluable Immunogenicity Population\nBooster response observed following a dose of MenABCWY vaccine 4 \nyears after a 2 dose primary series (0,6m) in ACWY -naïve participants\n100% of participants had ACWY hSBA titers ≥1:8 following a booster dose of MenABCWY vaccine at 4 years\nAbbreviations: hSBA=serum bactericidal assay using human complement; GMT= geometric mean titer; Post primary series =2 doses for MenABCWY and a single dose for MenACWY -CRM.\n*Number of subjects with valid and determinate hSBA titer for the given strain ranged from 59- 60 for MenABCWY and 35- 37 for MenB -fHbp + MenACWY -CRM. ^Pre booster= 4 years after \nsecond dose of MenABCWY and 4.5 years after single dose of MenACWY -CRM.\nData on File, Study B1971057 (NCT03135834) Aug 2022, Pfizer Inc.\nComparisons (ACWY -naïve participants):\n•MenABCWY vaccine 4 years^ after second dose (pre booster) and 1 month after \nbooster \n•MenACWY -CRM 4.5 years^ after single dose (pre booster) and 1 month after \nboosterA C W Y\n248163264128256512102420484096\nPost \nprimaryPre^ Post Post \nprimaryPre^ Post Post \nprimaryPre^ Post Post \nprimaryPre^ PostGMTGMTs* 4 years after primary vaccination and 1 month after booster for \nserogroups ACWY \nbooster booster booster booster\nMenABCWY MenB -fHbp + MenACWY -CRM\n14 Pfizer Confidential020406080100\nBaseline 1m PD2 12m PD2 24m PD2 36m PD2 48m PD2Percentage (%)A22†\nB24A56\nB44020406080100\nBaseline 1m PD2 12m PD2 24m PD2 36m PD2 48m PD2Percentage (%)\n020406080100\nBaseline 1m PD2 12m PD2 24m PD2 36m PD2 48m PD2\n020406080100\nBaseline 1m PD2 12m PD2 24m PD2 36m PD2 48m PD2\nMenABCWY MenB -fHbp + MenACWY -CRMMenB seroprotection up to 4 years after 2 doses of MenABCWYStudy B1971057  | mITT and Booster Evaluable Immunogenicity Populations\nPercentage of individuals* with hSBA titers ≥ 1:8†at all timepoints\nAbbreviations: hSBA=serum bactericidal assay using human complement; PD2=post dose 2.\n*Number of subjects with valid and determinate hSBA titer for the given strain ranged from 162- 212 for MenABCWY and 83- 137 for MenB -fHbp + MenACWY -CRM (Stage 2 mITT population [baseline through \n36m PD2]), and 121- 129 for MenABCWY and 81- 87 for MenB -fHbp + MenACWY -CRM (Booster evaluable immunogenicity population [48m PD2 Post Primary and Post Booster]).†hSBA ≥1:16 for A22.\nData on File, Study B1971057 (NCT03135834) Aug 2022, Pfizer Inc.\n15 Pfizer ConfidentialStudy B1971057 | Booster Evaluable Immunogenicity Population\nA22 A56 B24serogroup B\nB441024\n512\n256128\n64MT G\n3216\n84\n2\nPost Pre Post Post Pre Post Post Pre Post Post Pre Post\nprimary booster primary booster primary booster primary booster\nMenABCWY MenB -fHbp + MenACWY -CRMGMTs* 4 years after primary vaccination and 1 month after booster for \n•95.1-100% of participants had B hSBA titers ≥1:8^ following a booster dose of MenABCWY vaccine 4 years\nAbbreviations: hSBA=serum bactericidal assay using human complement; GMT= geometric mean tier; Post primary series (2 doses for both MenABCWY and MenB -fHbp ) \n*Number of subjects with valid and determinate hSBA titer for the given strain ranged from 121- 130 for MenABCWY and 81- 88 for MenB -fHbp + MenACWY -CRM. ^≥1:16 for A22 strain\nData on File, Study B1971057 (NCT03135834) Aug 2022, Pfizer Inc.Comparisons (B -naïve participants):\n•MenABCWY vaccine 4 years after second dose (pre booster) and 1 \nmonth after booster \n•MenB -fHbp 4 years after second dose (pre booster) and 1 month after \nbooster \nBooster response observed following a dose of MenABCWY vaccine 4 \nyears after a 2 dose primary series (0,6m) in B-naïve participants\n16 Pfizer ConfidentialImmunogenicity\nACWY-primed\n17 Pfizer Confidential0102030405060708090100\nA C W Y(%)Percentage of participants achieving hSBA seroresponse*1 month after \nvaccination for serogroups ACWY \nMenABCWY MenB -fHbp + MenACWY -CRM\n•1 dose of MenABCWY vaccine was noninferior to 1 dose of MenACWY -CRM in ACWY -primed participants\n•99.5-100% of participants had serogroups ACWY hSBA titers ≥1:8 after 1 dose of MenABCWY vaccineA single dose of MenABCWY vaccine can be used as an alternative to \nACWY vaccines in ACWY-primed adolescentsStudy C3511001 | Evaluable Immunogenicity Population\nAbbreviations: hSBA=serum bactericidal assay using human complement.\n*For participants with a baseline hSBA titer <1:4, seroresponse is defined as a titer ≥1:16. For those with a baseline hSBA titer ≥1:4 and <1:8, seroresponse is a titer ≥4 times the 1:8. For those with a baseline \nhSBA titer ≥1:8, seroresponse is a titer ≥4 times the baseline titer.\nN=428- 442 for MenABCWY group; N=222- 227 for MenB -fHbp + MenACWY -CRM group.\nData on File, Study C3511001 (NCT04440163) Aug 2022, Pfizer Inc. Comparisons (ACWY -primed participants): \n•MenABCWY vaccine 1 month after first dose \n•MenACWY -CRM 1 month after single dose\n\n18 Pfizer Confidential0102030405060708090100\nA C W Y A22 A56 B24 B44 Composite%Percentage of participants achieving hSBA seroresponse*1 month after \nvaccination\nMenB -fHbp +       MenACWY -CRM MenABCWYSerogroups ACWY Serogroup B\n•2 doses of MenABCWY vaccine were noninferior to 1 dose of MenACWY-CRM in ACWY- primed participants\n•99-100% had serogroups ACWY hSBA titers ≥1:8 after 2 doses of MenABCWY vaccine\n•100% of ACWY -primed participants have protective titers four years after 2 doses of MenABCWY vaccine (Study B1971057)2 doses of MenABCWY vaccine can be used as an alternative to 1 dose \nMenACWY -CRM and 2 doses MenB -fHbp in ACWY -primed adolescentsStudy C3511001 | Evaluable Immunogenicity Population\nAbbreviations: hSBA=serum bactericidal assay using human complement.\n*For participants with a baseline hSBA titer <1:4, seroresponse is defined as a titer ≥1:16. For those with a baseline hSBA t iter ≥1:4 and <1:8, seroresponse is a titer ≥4 times the 1:8. For those with a baseline \nhSBA titer ≥1:8, seroresponse is a titer ≥4 times the baseline titer.N=376- 387 for MenABCWY group; N=22- 227 for MenB -fHbp + MenACWY -CRM group.\nData on File, Study C3511001 (NCT04440163) and Study B1971057 (NCT03135834) Aug 2022, Pfizer Inc\nComparisons (ACWY -primed participants): \n•MenABCWY vaccine 1 month after second dose \n•MenACWY -CRM 1 month after single dose\nComparisons (All participants group B vaccine naive):\n•MenABCWY vaccine 1 month after second dose \n•MenB -fHbp 1 month after second dose\n19 Pfizer Confidential020406080100\nBaseline 1m PD2 12m PD2 24m PD2 36m PD2 48m PD2Percentage (%)\n020406080100\nBaseline 1m PD2 12m PD2 24m PD2 36m PD2 48m PD2A\nWC\nY020406080100\nBaseline 1m PD2 12m PD2 24m PD2 36m PD2 48m PD2Percentage (%)\n020406080100\nBaseline 1m PD2 12m PD2 24m PD2 36m PD2 48m PD2\nBaseline          7m PD1         18m PD1       30m PD1        42m PD1        54m PD1\nBaseline          7m PD1        18m PD1       30m PD1        42m PD1        54m PD1Baseline         7m PD1         18m PD1       30m PD1        42m PD1       54m PD1\nBaseline          7m PD1        18m PD1       30m PD1         42m PD1       54m PD1\nMenABCWY MenB -fHbp + MenACWY -CRMMenACWY seroprotection persists up to 4 years in ACWY -primed populationStudy B1971057 | mITT and Booster Evaluable Immunogenicity Populations\nPercentage of participants* (95% CI) with hSBA titers ≥ 1:8\nAbbreviations: hSBA=serum bactericidal assay using human complement; PB=post booster; PD1=post dose 1; PD2=post dose 2.\n*Number of subjects with valid and determinate hSBA titer for the given strain. Lower N for groups A, W, Y compared to C due to receipt of monovalent C vaccine prior to study entr y. \nFor groups A, W, and Y, N=48- 61 for MenABCWY and 22- 38 for MenB -fHbp + MenACWY -CRM (Stage 2 mITT population [baseline through 36m PD2/42m PD1]), and 32- 33 for MenABCWY and 16- 17 for MenB -\nfHbp + MenACWY -CRM (Booster evaluable immunogenicity population [48m PD2 /54m PD1 Post Primary and Post Booster]). For group C, N=54- 100 for MenABCWY and 23- 72 for MenB -fHbp + MenACWY -\nCRM (Stage 2 mITT population), and 68- 70 for MenABCWY and 51 for MenB -fHbp + MenACWY -CRM (Booster evaluable immunogenicity population).\nData on File, Study B1971057 (NCT03135834) Aug 2022, Pfizer Inc.\n20 Pfizer ConfidentialSafety\n21 Pfizer ConfidentialLocal reactions*within 7 days after vaccinationLocal reactogenicity by doseStudy C3511001 | Safety Population\n0255075100 Percentage of participants (%)\n0255075100Dose  1\nPain† Redness‡Swelling‡MenABCWY MenB -fHbp MenABCWY MenB -fHbp MenABCWY MenB -fHbpMenABCWY MenB -fHbp MenABCWY MenB -fHbp MenABCWY MenB -fHbp89.3% 85.1%\n25.8%\n19.5%24.9%21.4%\n84.4%78.6%\n23.2%\n14.7%24.2%\n14.7%Dose  2\nPercentage of participants (%)\n*Local reactions are summarized only for the left arm, which is the MenABCWYvaccine or MenB+fHbp injection site; †Mild=does not interfere with activity, moderate=interferes with activity, severe=prevents daily activity. \n‡Mild=>2.0 to 5.0 cm, moderate=>5.0 to 10.0 cm, and severe is >10.0 cm.\nData on File, Study C3511001 (NCT04440163) Aug 2022, Pfizer Inc.Mild Moderate SevereSeverity10-25 years\nNo differences observed between: ACWY -Naïve and Primed participants or Primary and Booster vaccination\n22 Pfizer ConfidentialSystemic events within 7 days after vaccinationSystemic reactogenicity by doseStudy C3511001 | Safety Population\n1   e Dos 2   e Dos0255075100\nMenABCWY MenB -fHbp + \nMenACWY -CRM*46.8%52.1%54.7%\n25.7%27.4%\n20.2%22.6%46.9%\nFatigue† Headache† Muscle Pain† Joint Pain†Percentage of participants (%)\nMenABCWY MenB -fHbp + \nMenACWY -CRM*MenABCWYMenB -fHbp + \nMenACWY -CRM*MenABCWY MenB -fHbp + \nMenACWY -CRM*\n0255075100\n39.8%47.6%43.6%\n22.8% 22.2% 18.3%15.6%37.8%\nMenABCWY MenB -fHbp * MenABCWYMenB -fHbp * MenABCWY MenB -fHbp * MenABCWY MenB -fHbp *Percentage of participants (%)Mild Moderate SevereSeverity\n*MenB -fHbp + MenACWY -CRM group: MenB -fHbp and MenACWY -CRM given at dose 1 and 3, MenB -fHbp given at dose 2.  \n†Mild: does not interfere with activity; Moderate: some interference with activity; Severe: prevents daily routine activity.\nData on File, Study C3511001 (NCT04440163) Aug 2022, Pfizer Inc.10-25 years\nNo differences observed between: ACWY -Naïve and Primed participants or Primary and Booster vaccination\n23 Pfizer Confidential0255075100Dose  1 Dose  2MenABCWY MenB -fHbp + \nMenACWY -CRM*11.0%20.1% 19.6%\n3.2% 3.0%5.9% 5.8%13.5%\nChills† Diarrhea‡ Vomiting§ FeverǁMenABCWY MenB -fHbp + \nMenACWY -CRM*MenABCWYMenB -fHbp + \nMenACWY -CRM*MenABCWY MenB -fHbp + \nMenACWY -CRM*\n0255075100\n8.2%16.4% 16.2%\n1.5% 0.9% 2.3% 1.5%8.5%\nMenABCWY MenB -fHbp * MenABCWYMenB -fHbp * MenABCWY MenB -fHbp * MenABCWY MenB -fHbp *Percentage of participants (%) Percentage of participants (%)38.0- 38.4 39.0- 40.0 38.5- 38.9Systemic events within 7 days after vaccinationSystemic reactogenicity by doseStudy C3511001 | Safety Population\n*MenB -fHbp + MenACWY -CRM group: MenB -fHbp and MenACWY -CRM given at dose 1 and 3, MenB -fHbp given at dose 2. †Mild: does not interfere with activity; Moderate: some interference with activity; \nSevere: prevents daily routine activity. ‡Mild: 2 –3 loose stools in 24 hours; Moderate: 4– 5 loose stools in 24 hours; Severe: 6 or more loose stools in 24 hours. \n§Mild: 1 –2 times in 24 hours; Moderate: >2 times in 24 hours; Severe: requires intravenous hydration. ǁNofevers >40oCwere reported.\nData on File, Study C3511001 (NCT04440163) Aug 2022, Pfizer Inc.10-25 years\nModerate Mild SevereSeverity\nFever Severity (oC)\nNo differences observed between: ACWY -Naïve and Primed participants or Primary and Booster vaccination\n24 Pfizer ConfidentialNumber (%) of participants reporting ≥ 1 adverse event during the vaccination phase*\nMenABCWY + Saline\nN=1763MenB-fHbp + MenACWY -CRM\nN=649\nEndpointn % (95% CI)Number of\nEvents n % (95% CI)Number of\nEvents\nAll AEs 368 20.9 (19.0, 22.8) 638 132 20.3 (17.3, 23.6) 202\nRelated 11 0.6 (0.3, 1.1) 19 4 0.6 (0.2, 1.6) 5\nSevere 13 0.7 (0.4, 1.3) 17 4 0.6 (0.2, 1.6) 4\nAll SAEs 7 0.4 (0.2, 0.8) 9 0 0 (0.0, 0.6) 0\nRelated 0 0 (0.0, 0.2) 0 0 0 (0.0, 0.6) 0\nAll MAEs 263 14.9 (13.3, 16.7) 436 93 14.3 (11.7, 17.3) 141\nRelated 2 0.1 (0.0, 0.4) 2 1 0.2 (0.0, 0.9) 1\nSevere 8 0.5 (0.2, 0.9) 9 3 0.5 (0.1, 1.3) 3\nAll NDCMCs 20 1.1 (0.7, 1.7) 23 2 0.3 (0.0, 1.1) 2\nRelated 0 0 (0.0, 0.2) 0 0 0 (0.0, 0.6) 0\nSevere 1 <0.1 (0.0, 0.3) 2 0 0 (0.0, 0.6) 0Study C3511001 | Safety Population\nAbbreviations: AE=adverse event; MAE=medically attended event (nonserious AE that results in an evaluation at a medical facil ity); NDCMC=newly diagnosed chronic medical condition (a disease \nor medical condition, not previously identified, that is expected to be persistent or is otherwise long- lasting in its effects); SAE=serious adverse event.\n*Vaccination phase refers to the time from the first study vaccination (Visit 1) through 1 month after the second study vacci nation (Visit 4).\nData on File, Study C3511001 (NCT04440163) Aug 2022, Pfizer Inc.\nHigher number of NDCMCs of ADHD in the MenABCWY group – most of them with ADHD- related symptoms before \nentering the study10-25 years\n25 Pfizer ConfidentialOverall conclusion: Data support the use of MenABCWY vaccine in the \nUS adolescent meningococcal vaccination platform\n•MenABCWY vaccine was safe and well tolerated in adolescents and young adults\nSafety\n•A single dose of MenABCWY vaccine can be used as an alternative to ACWY vaccines in \nACWY -naïve or primed adolescents and young adults\nACWY protection\n•MenABCWY vaccine protects against all 5 serogroups with 2 doses given 6 to 12 months \napart\n•Booster response was observed following a dose of MenABCWY vaccine 4 years after a 2 dose primary series (0,6m) for all 5 serogroups\n•If 2 doses of MenABCWY vaccine are administered at 11-12 yrsof age, data support that a \nsingle (booster) dose from 16 years of age can provide protection against all 5 serogroups\nABCWY protection\n26 Pfizer ConfidentialPfizer wishes to thank: \n•The clinical trial participants\n•Sites, investigators, CRO, our partners, and their staffA\ncknowledgements", "summary": "1 Pfizer ConfidentialMenABCWY  Meningococcal  Vaccine Jason D. Maguire, MD, MPH Clinical Lead, Phase 3 Program  Pfizer Vaccines Clinical R&D 2 Pfizer Confidential For Internal and Restricted Pfizer Use Only –Not for Distribution. Privileged and Confidential.MenABCWY vaccine composition Confidential•MenABCWY vaccine is composed of drug substance from: –Trumenba®(MenB-fHbp): licensed in the US for the prevention of invasive disease caused by Neisseria meningitidis group  B in individuals 10…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/Mening-03-Maguire-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 26}
{"title": "Mening 04 Crowe 508", "content": "National Center for Immunization & Respiratory Diseases \nWork Group Interpretation of Pfizer’s \nMenABCWY Vaccine Clinical Trials Data \nSam Crowe, PhD, MPH \nMeningococcal Vaccines Work Group Lead \nFebruary 23, 2023 \n     \n          \n       \n \n    \n           \n     \n    \n           \n    \n     \n              Policy Questions for Each Pentavalent Vaccine \n Should the pentavalent vaccine be included as an option for \nMenACWY/MenB vaccination in people currently recommended to receive both vaccines? \n– For e\nxample, 16 year olds1 \n Should the pentavalent vaccine be included as an option for people currently recommended to receive MenACWY only? \n– For e\nxample, 11–12 year olds \n Should the pentavalent vaccine be included as an option for people currently recommended to receive MenB only? \n– For e\nxample, during a serogroup B outbreak \n116 year olds who decide to receive the MenB vaccine based on shared clinical decision-making 2 \n\n     \n        \n         \n           \n     \n      \n      \n       \n        \n      \n    \n      \n    Pfizer MenABCWY Vaccine and Trials Overview \n Comprised of Nimenrix (serogroups ACWY) and Trumenba (serogroup B) \n– Trumenba currently licensed and available in US, 10y through 25y \n– Nimenrix not licensed in US but used extensively elsewhere, 6w and older \n Two clinical trials completed (NCT03135834, NCT04440163) \n– Assessed safety and immunogenicity of pentavalent vaccine \n– Compared to Trumenba (MenB) and Menveo (MenACWY) \n– Included participants 10 through 25 years of age \n– Studied single and two dose (0, 6m) schedules \n– 4-year persistence and booster dose were evaluated \n Extended interval study underway (NCT04440176) \n– Study arm 1 — 0, 12m (data available) \n– Study arm 2 — 0, 36m \n3 \n          \n          \n  \n      \n    \n      \n             \n  \n      \n           \n          \n    \n          Safety \n Assessed by monitoring for and comparing local reactions, systemic events, \nmedically attended adverse events, serious adverse events, and newly diagnosed chronic medical conditions \n Local reactions within 7 days after vaccination \n– Includes pain, redness, swelling \n– Comp\narison between pentavalent and MenB vaccine only \n– Slig\nhtly higher percentage of participants had a local reaction to pentavalent vaccine for \nboth 1st and 2nd doses \n Systemic events within 7 days after vaccination \n– Includes fatigue, headache, muscle pain, joint pain, chills, diarrhea, vomiting, fever \n– Simi\nlar percentage of participants experienced systemic events in pentavalent vaccine \ngroup and in MenACWY+MenB group \n– Perc\nentage varied slightly between groups by systemic event and by dose \n4 \n \n   \n      \n  \n       \n             \n  \n     \n       \n         \n        \n         Safety, Continued \n Medically attended adverse events \n– Sim\nilar percentages between study groups (both <15%) \n Serious adverse events \n– Mor\ne reported for pentavalent group (0.4% vs. 0%) \n– Non\ne assessed to be related to pentavalent vaccine (e.g., hospitalization due to other \nmedical conditions) \n Newly diagnosed chronic medical conditions (NDCMC) \n– Mor\ne reported for pentavalent group (1.1% vs. 0.3%) \n– Hig\nher number of participants with attention-deficit/hyperactivity disorder (ADHD) in \npentavalent group – most with related symptoms before entering study \n Higher risk patients (e.g., complement deficiency) not included in trials \n5 \n \n     \n       \n           \n          \n \n        \n   \n  \n          Immunogenicity Standards \n Serogroups A, C, W, and Y \n– Percen\ntage of participants achieving MenACWY seroresponse in hSBA \ntiter 1 month after 1 dose and 1 month after 2 doses \n– Seroresponse is defined as a 4-fold increase in titer over baseline \n Serogroup B \n– Perc\nentage of participants achieving MenB seroresponse in hSBA 1 \nmonth after 2 doses \n– Composite response provided \n– Seroresponse is defined as a 4-fold increase in titer over baseline \n6 \n      \n               \n       \nImmunogenicity for Serogroups A, C, W, Y \n 1 dose of the pentavalent vaccine is noninferior to 1 dose of MenACWY in both \nACWY-naïve and ACWY-primed participants 1 month after administration \nACWY-Naive ACWY-Primed \n7 \n      \n               \n           Immunogenicity for Serogroups A, C, W, Y \n 2 doses of the pentavalent vaccine given 6 months apart are noninferior to 1 dose \nof MenACWY in both naïve and primed participants 1 month after administration \nACWY-Naive ACWY-Primed \n8 \n       \n            Seroprotection for ACWY-Naïve Participants after 4 Years \n Seroprotection persists up to 4 years in naïve participants after a 2-dose series \n9 \n       \n            Seroprotection for ACWY-Primed Participants after 4 Years \n Seroprotection persists up to 4 years in primed participants after a 2-dose series \n10 \n   \n               \n       Immunogenicity for Serogroup B \n 2 doses of the pentavalent vaccine given 6 months apart are noninferior to 2 doses \nof MenB in naïve participants (primed not assessed) \n11 \n\n    \n             \n        Seroprotection for Serogroup B-Naïve Participants \n Waning of immunity for the pentavalent vaccine is very similar to that observed \nwith MenB, dropping substantially by 12 months post-dose 2 \n12 \n\n   \n        \n        \n         \n        \n     \n           Additional Work Group Reflections \n Data not presented on 3-dose schedule of pentavalent vaccine \n–\n 3\n-dose schedule of Trumenba currently recommended for certain \nhigh-risk groups (e.g., people affected by a serogroup B outbreak) \n\n Data not available in people older than 25 years \n–\n M\nenB vaccines licensed for 10–25 years \n–\n M\nenACWY vaccines licensed up to 55 years or older depending on \nvaccine \n13 \n    \n          \n    \n \n    \n    \n \n        \n        \n     Final Reflections and Next Steps \n Pfizer’s MenABCWY vaccine appears to be noninferior to MenACWY+MenB based \non clinical trial data presented \n\n Data gaps \n–\n 3-dose schedule for high-risk populations \n– Adults older than 25 years \n\n Next steps \n–\n Reviewing additional immunologic persistence data for a single dose \n– GRADE and EtR — will focus on pentavalent vaccine studies \n– Cost effectiveness study will be conducted \n14 \n    \n \n      \n                        \n   For more information, contact CDC \n1-800-CDC-INFO (232-4636) TTY: 1-888-232-6348 www.cdc.gov \nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.", "summary": "National Center for Immunization & Respiratory Diseases  Work Group Interpretation of Pfizer’s  MenABCWY Vaccine Clinical Trials Data  Sam Crowe, PhD, MPH  Meningococcal Vaccines Work Group Lead  February 23, 2023                                                                                              Policy Questions for Each Pentavalent Vaccine   Should the pentavalent vaccine be included as an option for  MenACWY/MenB vaccination in people currently recommended to receive both…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/Mening-04-Crowe-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 15}
{"title": "Polio 01 Brooks 508", "content": "Centers for Disease Control and Prevention\nNational Center for Immunization and Respiratory DiseasesCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory DiseasesCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention \nNational Center for Immunization and Respiratory Diseases \nACIP Polio Vaccination Work Group \nOliver Brooks, MD, FAAP \nACIP Meeting February 23, 2023 \nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. \n\n           \n          \n         \n      \n            \n         \n             \n               \n   Polio Vaccination Work Group Terms of Reference \nPolicy topics under consideration: \n1) Whether more specific guidance on adult vaccination , including use of adult \nbooster doses, can be provided in the context of circulating poliovirus. \n2) Whether adults who are immunocompromised should be recommended an \nadditional adult booster of a polio-containing vaccine. \n3) Whether fractional doses of IPV (fIPV), as prequalified by WHO, should m eet polio \nvaccination requirements, including for people immigrating to the United States. \n4) Consider criteria under which novel Oral Polio Vaccine type 2 (nOPV2) might be \nused in areas with outbreaks or persistent circulation of poliovirus.", "summary": "Centers for Disease Control and Prevention National Center for Immunization and Respiratory DiseasesCenters for Disease Control and Prevention National Center for Immunization and Respiratory DiseasesCenters for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention  National Center for Immunization and Respiratory Diseases  ACIP Polio Vaccination Work Group  Oliver Brooks, MD, FAAP  ACIP Meeting February 23, 2023 …", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/Polio-01-Brooks-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 2}
{"title": "Polio 02 Kidd 508", "content": "CCCCenen enentt ttererer ers sss     f fffo ooorrr    r DiDi DiDiss sseaea eaeassssee e    e CCCCoooonnnnttt trrr roooollll     aaaannnndddd     PP PPrr rreeeevvvvenenenenttttiii iooo onnnn \nNNN Naaaatttti iiio ooonn nnaaaallll    CC CCeeeennnnttt tee eerrrr    ffffoooorrrr    II IImmmmmm mmuuuunnnni iiiz zzza aaat ttti iiio ooonn nn    aaaann nndddd    RR RReeeespsp spspiii ir rrra aaattttoo oorrrryyyy    DDDDiiiisese sesea aaase sesesess ss \nAdult Polio Vaccination \nSarah Kidd, MD, MPH \nACIP Meeting February 23, 2023 \nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. \n\n        \n         \n  \n            \n      Objectives for Today’s Presentation \n Briefly summarize work group deliberations on adult polio vaccination \n Present proposed language for adult polio vaccination (anticipate ACIP \nvote in June) \n Solicit feedback and identify areas where more data are needed prior to an ACIP vote \n\n             \n     \n            \n  \n                 \n            \n  \n      2000 Recommendations for Inactivated Polio Vaccine (IPV) \nVaccination of Adults \n Vaccination is recommended for certain adults who are at greater risk for exposure \nto polioviruses than the general population \n Unvaccinated adults who are at increased risk should receive a primary vaccination series with IPV \n Adults who have had a primary series of OPV or IPV and who are at increased risk can receive another dose of IPV \nPoliomyelitis Prevention in the United States (cdc.gov) \n\n          \n           \n   \n        \n   \n               \n       \n      2000 Statement on IPV Vaccination for Adults \nQuestions and problems that came up in 2022 \n 2000 statement focused on adults atincreased risk of poliovirus exposure \n Unclear how to define increased risk in setting of circulating vaccine-derived \npoliovirus (cVDPV) in US \n Unclear recommendation for unvaccinated adults who were not considered at \nincreased risk of exposure \n Unclear recommendation for vaccinated adults and when/if a booster was advised \nPoliomyelitis Prevention in the United States (cdc.gov) \n\n            \n        \n             \n        \n      \n \n   \n        \n    \n             Policy Question #1 for Work Group \n Should completion of a primary polio vaccination series with IPV be recommended \nfor unvaccinated and incompletely vaccinated adults in the US? \n– Population: Unvaccinated and incompletely vaccinated (with OPV or IPV) US adults aged >18 years \n– Intervention: Completion of a primary vaccination series with IPV \n– Comparison: No vaccination or partial series completion \n– Outcomes: \n• Prevention of paralytic poliomyelitis \n• Serologic immunity to poliovirus types 1, 2, and 3 \n• Serious adverse events following vaccination \n• Indirect effects, e.g., community transmission, impact on health systems \n\n        \n               \n   \n            \n                 \n      Current Definition of Fully Vaccinated \nAn adult is considered fully vaccinated if they received: \n– \n– \n– A primary series of ≥3 doses of trivalent OPV (tOPV) or IPV in any combination \nadministered ≥4 weeks apart \nAND \nThe last dose in the series was given on or after the 4th birthday \nAND \nThe last dose in the series was given ≥6 months after the previous dose \nPoliomyelitis Prevention in the United States (cdc.gov ) \n\n    \n   \n      \n   \n     \n     \n       Public Health Problem \n Poliovirus infection can cause \npoliomyelitis and lifelong paralysis \n– Paralytic disease occurs in <1% of \ninfections (varies by serotype) \n– Non-paralytic clinical illness occurs in ~25%, including 1%–5% with aseptic meningitis \n– Approximately 75% of infections are asymptomatic \n\n        \n   \n  \n      \n     \n   \n    \n   1950\n1960\n1970\n1980\n1990\n2000\n2010\n2020Number of poliomyelitis cases 20000 \n15000 \n10000 \n5000 \n0 Paralytic polio decreased rapidly in the US after \nintroduction of polio vaccine \n25000 \n1994: Americas \ncertified polio-free 1955: Salk IPV \n1961: Sabin OPV 1979: Last indigenous \nWild-type case in US \n2000: IPV only 1997: Sequential enhanced-potency \nIPV followed by OPV 1952 \n1954 1956 1958 \n1962 \n1964 1966 1968 \n1972 \n1974 \n1976 1978 \n1982 \n1984 \n1986 \n1988 \n1992 \n1994 \n1996 \n1998 \n2002 \n2004 2006 2008 \n2012 \n2014 2016 2018 \nYear \n\n       \n      \n   \n \n   \n \n   Global Paralytic WPV1 and cVDPV Cases1, Previous 12 Months2 \nWPV1 cases (latest onset) \nPakistan 20 15-Sep-22 \nAfghanistan 1 29-Aug-22 \nMozambique 8 10-Aug-22 \ncVDPV1 cases (latest onset) DR Congo 92 16-Dec-22 Malawi 4 01-Dec-22 Mozambique 19 20-Nov-22 \nMadagascar 11 25-Sep-22 \ncVDPV2 cases (latest onset) Indonesia 2 03-Jan-23 CAR 5 26-Dec-22 \nAlgeria 3 13-Dec-22 DR Congo 260 10-Dec-22 Yemen 121 02-Dec-22 Chad 36 11-Nov-22 \nSudan 1 31-Oct-22 Cameroon 2 30-Oct-22 Niger 13 27-Oct-22 \nNigeria 29 27-Oct-22 Mali 1 26-Oct-22 \nBenin 10 09-Oct-22 \nTogo 1 30-Sep-22 \nGhana 3 14-Sep-22 Somalia 4 23-Aug-22 \nUSA 1 20-Jun-22 \nEthiopia 1 01-Apr-22 \nMozambique 4 26-Mar-22 Eritrea 1 02-Mar-22 \ncVPDV3 case (latest onset) \nIsrael 1 12-Feb-22 \nPolio Now – GPEI (polioeradication.org ) \n\n        \n             \n           \n  \n         \n      \n           \n             \n           \n      Paralytic Polio Case in New York State, July 2022 \n• A case of paralytic polio caused by vaccine-derived poliovirus type 2 (VDPV2) was \nconfirmed in an unvaccinated young adult from Rockland County, New York, on July 21, 2022 \n• Genetic sequencing has indicated a linkage to polioviruses collected in wastewater in Israel, United Kingdom, and Canada \n• Rockland County has reported overall low vaccine coverage for over 20 years \n• In summer 2022, 60% of children under 2 yrs of age had received the recommended 3 doses of IPV (zip code level as low as 37%) \n• No additional paralytic cases have been identified \n\n         \n        \n       \n       \n \n       \n        \n   \n        Wastewater Testing for Poliovirus \n Poliovirus type 2 genetically linked to the case detected \nin wastewater samples in New York (Rockland, Orange, Sullivan, and Nassau counties and New York City) \n Retrospective testing detected poliovirus as early as April 2022 \n Most recent positive sample was collected on December 15, 2022; no detections in samples collected in last 7 weeks \n No additional paralytic polio cases identified \n\n    \n          \n     \n     \n    \n           \n    \n       –Seroprevalence of Poliovirus Antibodies by Age, \nUnited States NHANES Serosurvey, 2009–2010 \nPercent positive (95% Confidence Interval) \nBirth years Age in 2009 2010 Poliovirus Type 1 Poliovirus Type 2 Poliovirus Type 3 \n1998–2004 6–11 years 97.2 (94.7–98.8) 98.0 (96.4–99.0) 93.8 (91.8–95.4) \n1990–1998 12–19 years 94.7 (92.0–96.6) 98.2 (96.6–99.2) 84.3 (81.0–87.2) \n1970–1990 20–39 years 92.7 (90.0–94.2) 96.9 (95.2–98.2) 78.6 (74.6–82.2) \n1960–1970 40–49 years 93.9 (91.6–95.7) 95.8 (93.8–97.3) 85.8 (82.3–88.8) \nSource: Wallace et al, BMC Public Health 2016. \n\n           \n \n            \n     \n    \n    \n      \n   \n   \n           \n     \n            Effectiveness of Enhanced-Potency IPV \n Presence of detectable neutralizing antibody is a correlate of protection against \nparalytic disease. \n– Immunity against paralytic disease may be present even in absence of detectable antibodies. \n Serologic immunogenicity among infants and children1 \n– 70%–100% seropositive after 2 doses \n– 88%–100% seropositive after 3 doses \n Estimates of vaccine effectiveness against paralytic polio2 \n– 36%–89% for 1 dose \n– 89%– 98% for 2 doses \n Paucity of data on adults receiving a primary series \n1. Vidor et al review, PIDJ 1997. \n2. Stoeckel et al, Rev Infect Dis 1984. CDC, MMWR 1988. John, Rev Med Virol 1993. \n\n \n             \n            \n              \n    \n  \n                 \n \n    \n                 IPV and Mucosal Immunity \n Intestinal immunity1 \n– No significant difference between IPV and unvaccinated individuals in the odds of shedding \n– IPV vaccination appears to reduce the mean quantity of shed poliovirus by 63%–91% \n– Some data to suggest that IPV vaccination reduces duration of shedding ;recent modeling study \nindicated no impact of IPV \n Nasopharyngeal (NP) immunity2 \n– Evidence to suggest similar, low rates of NP shedding (0%–4%) among OPV and IPV vaccinees \nSources: \n1. Hird and Grassly meta-analysis, PLoS Pathogens 2012. \n2. Kok et al, Bulletin of WHO 1992. Onorato et al, JID 1991. Brouwer et al, J R Soc Interface 2022. \n\n       \n  \n  \n  \n            \n          \n             \n     \n                       Safety: IPV is well-tolerated. \n Local reactions at injection site reported in trials \n– Tenderness in 14%–29% \n– Induration in 3%–11% \n– Erythema in 0.5%–1.4% \n Combining IPV with other vaccines is not associated with increased frequency or \nseverity of reported adverse reactions compared with the other vaccines alone \n No severe adverse events have been causally associated with use of the current formulation of IPV \nSources: Sanofi Pasteur Package Insert - IPOL (fda.gov) . Vidor et al, PIDJ 1997. Murdin et al, Vaccine 1996. Wattigney et al, Pediatrics 2001. IOM 1994. \n\n      \n       \n      \n       \n         \n       \n        \n                \n       Vaccine Adverse Event Reporting System (VAERS) Data, \n2000–2012 \n >250 million IPV-containing vaccine doses distributed 2000–2012 \n 41,792 adverse event reports submitted for IPV-containing vaccines \n– 34,880 (88%) were for non-serious events \n– 95% were among persons <7 years of age \n Most events were associated with IPV co-administered with other vaccines \n Standalone IPV accounted for just 0.5% of reports \n VAERS is passive reporting system, cannot assess causal associations \n Reported adverse events were similar and proportional to other vaccines \nSource: Iqbal et al, Lancet ID 2015. \n\n         \n  \n          \n       \n        \n  \n         \n        \n       \n        \n  \n        \n            \n   Considerations for a Risk-Based vs. Uniform \nRecommendation for Unvaccinated Adults \nSituations that put adults at increased risk of exposure \nto poliovirus include: \n Travelers who are going to countries where polio is epidemic or \nendemic (For additional information, see Polio: For Travelers). \n Laboratory and healthcare workers who handle specimens that \nmight contain polioviruses. \n Healthcare workers or other caregivers who have close contact \nwith a person who could be infected with poliovirus. \n Unvaccinated or incompletely vaccinated adults whose children \nwill be receiving oral poliovirus vaccine (for example, international \nadoptees or refugees). \n Unvaccinated or incompletely vaccinated adults living or working \nin a community where poliovirus is circulating. \n\n         \n  \n          \n       \n        \n  \n         \n        \n       \n        \n  \n        \n            \n   Considerations for a Risk-Based vs. Uniform \nRecommendation for Unvaccinated Adults \nSituations that put adults at increased risk of exposure \nto poliovirus include: \n Travelers who are going to countries where polio is epidemic or \nendemic (For additional information, see Polio: For Travelers). • Individual-level; \n Laboratory and healthcare workers who handle specimens that • Opportunity  to  \nanticipate  risk an d \nvaccinate  prior  to  \npotential  exposure  might contain polioviruses. \n Healthcare workers or other caregivers who have close contact \nwith a person who could be infected with poliovirus. \n U nvaccinated or incompletely vaccinated adults whose children \nwill be receiving oral poliovirus vaccine ( for example, international \nadoptees or refugees). \n Unvaccinated or incompletely vaccinated adults living or working \nin a community where poliovirus is circulating. \n\n         \n  \n          \n       \n        \n  \n         \n        \n       \n        \n  \n        \n            \n   \n   \n   \n   \n  \n  \n   Considerations for a Risk-Based vs. Uniform \nRecommendation for Unvaccinated Adults \nSituations that put adults at increased risk of exposure \nto poliovirus include: \n Travelers who are going to countries where polio is epidemic or \nendemic (For additional information, see Polio: For Travelers). \n Laboratory and healthcare workers who handle specimens that \nmight contain polioviruses. \n Healthcare workers or other caregivers who have close contact \nwith a person who could be infected with poliovirus. \n Unvaccinated or incompletely vaccinated adults whose children \nwill be receiving oral poliovirus vaccine (for example, international • Population-level; \n• Group already at \nincreased risk at time risk is recognized; \n• Potential missed opportunities for \nadoptees or refugees). vaccination prior to \n Unvaccinated or incompletely vaccinated adults living or working exposure in a community where poliovirus is circulating. \n\n            \n           \n            \n     \n          \n              \n    Pros and Cons of a Uniform Recommendation for \nUnvaccinated and Incompletely Vaccinated Adults \nPros: \n Allows unvaccinated adults and their health care providers to take advantage of \nopportunities to get vaccinated before they are at increased risk of exposure \n Brings adult polio vaccination policy closer in line with other routine childhood vaccines, e.g., MMR and varicella vaccines \n Is less complicated policy to communicate and understand (i.e., recommendation doesn’t change based on latest wastewater data) \n\n               \n           \n             \n           \n                       \n    Pros and Cons of a Uniform Recommendation for \nUnvaccinated and Incompletely Vaccinated Adults \nCons: \n Most adults in the United States have a low risk of poliovirus exposure and paralytic \npolio, and most adults received primary polio vaccination series as children \n Demand for IPV could potentially exceed supply, particularly if a large number of adults without documentation of polio vaccination status assume they were not vaccinated \n– However, this issue can be mitigated by providing guidance for this group in the clinical \nconsiderations \n\n           \n       \n \n            \n         \n \n              \n               \n         \n Proposed Language for Unvaccinated and Incompletely \nVaccinated Adults \n Majority of work group believe pros of uniform recommendation outweigh cons; \napproximately 1/3 favor maintaining the current risk-based recommendation \nMajority Recommendation : \nAdults who are known or suspected to be unvaccinated or incompletely vaccinated against polio should complete a primary vaccination series with IPV. \nClinical Considerations : \nIn general, unless there are specific reasons to believe they were not vaccinated, most \nadults who were born and raised in the United States can assume they were vaccinated against polio as children. \n\n              \n      \n               \n       \n    \n             \n \n   \n        \n    \n             Policy Question #2 for Work Group \n Should a booster IPV dose be recommended for adults in the US who have \npreviously completed a primary polio vaccination series? \n– Population: US adults aged >18 years who have completed a primary polio vaccination series (with \ntrivalent OPV, IPV, or a combination of both) \n– Intervention: Booster dose of IPV \n– Comparison: Adults who completed a primary series but did not receive a booster dose \n– Outcomes: \n• Prevention of paralytic poliomyelitis \n• Serologic immunity to poliovirus types 1, 2, and 3 \n• Serious adverse events following vaccination \n• Indirect effects, e.g., community transmission, impact on health systems \n\n                \n               \n            \n       \n              \n             \n                \n          \n     Boosters: 2000 Statement and Rationale \n 2000 Statement: “ Adults who have had a primary series of OPV or IPV and who are \nat increased risk can receive another dose of IPV. Available data do not indicate the \nneed for more than a single lifetime booster dose with IPV for adults .” \n Rationale \n– Longstanding recommendation since tOPV was used in routine immunization \n– Actual need for supplementary dose not established, but “there is value in assuring protection \nagainst infection with wild polioviruses when exposure can reasonably be expected.” (1977 ACIP Statement) \n– At least 2 reported cases of paralytic polio in adult travelers who had completed a primary vaccination series with Salk IPV and/or tOPV \nCDC MMWR 1977; CDC MMWR 1986. \n\n    \n          \n     \n     \n    \n            \n        \n  \n                    \n            –Unclear Need for IPV Booster in Vaccinated Adults: \nSeroprevalence of Poliovirus Antibodies by Age, United States \nNHANES Serosurvey, 2009–2010 \nPercent positive (95% Confidence Interval) \nBirth years Age in 2009 2010 Poliovirus Type 1 Poliovirus Type 2 Poliovirus Type 3 \n1998–2004 6–11 years 97.2 (94.7–98.8) 98.0 (96.4–99.0) 93.8 (91.8–95.4) \n1990–1998 12–19 years 94.7 (92.0–96.6) 98.2 (96.6–99.2) 84.3 (81.0–87.2) \n1970–1990 20–39 years 92.7 (90.0–94.2) 96.9 (95.2–98.2) 78.6 (74.6–82.2) \n1960–1970 40–49 years 93.9 (91.6–95.7) 95.8 (93.8–97.3) 85.8 (82.3–88.8) \nNOTE: Presence of detectable neutralizing antibody is a correlate of protection against paralytic disease. \nImmunity against paralytic disease may be present even in absence of detectable antibodies. \nSource: Wallace et al, BMC Public Health 2016. \n\n       \n      \n      \n  \n   \n      \n       \n       \n                          \n             \n      \n      \n Benefits of IPV Booster \n No data on vaccine effectiveness of primary \nseries + booster vs. primary series only \n Serologic studies in adults with heterogeneous pre-booster vaccination histories/seropositivity: 98%–100% were \nseropositive 1 month after an IPV-containing booster \n One study followed up trial participants 10 years post-booster: 98%–100% still seropositive Data from Grimprel et al, Vaccine 2005: \nSeropositivity before and 1 month after IPV -\ncontaining booster by study group and poliovirus serotype \nSources: Broderick et al, Vaccine 2015; Domenicus et al, Vaccine 2014; Fukushima et al, Vaccines 2022; Grimprel et al, Vaccine 2005; Kovac et al, Vaccine 2015; Larnaudie et al, \nHuman Vaccines 2010; Zimmermann et al, Vaccine 2013. \n\n  \n \n              \n             \n              \n            \n    Strong Majority of Work Group Agree with Current \nRecommendation for Adult IPV Booster \n Risk-based \n Shared clinical decision-making \nProposed Language: \n Adults who have received a primary series of tOPV or IPV in any combination and \nwho are at increased risk of poliovirus exposure may receive another dose of IPV. \nAvailable data do not indicate the need for more than a single lifetime booster dose with IPV for adults. \n\n        \n  \n  \n \n      \n       \n    \n     \n       \n       \n       \n       \n     \n      \n         \n     \n      \n      \n \n  \n   \n  \n \n \n \n \n \n \n \n \n \n \n \n \n \n  \n \n Thank you to \n ACIP voting members \n– Oliver Brooks (Chair) \n– Lynn Bahta \n Liaisons the ACIP Polio Work Group Members \n– Lynn Fisher, American Academy of Family Physicians \n– Chandy C John, American Academy of Pediatrics \n– Sandra Fryhofer, American Medical Association \n– Kathy Kudish, Association of Immunization Managers \n– Marcus Plescia, Association of State and Territorial Health Officials \n– Paul R Cieslak, Council of State and Territorial Epidemiologists \n– Christine Hahn, Council of State and Territorial Epidemiologists \n– Tina Q. Tan, Infectious Diseases Society of America \n– Adenike Shoyinka, Infectious Diseases Society of America \n– Mary Wilson, International Society of Travel Medicine \n– Jaqueline Lawler, National Association of County and City Health Officials \n– Kathy Edwards, Pediatric Infectious Diseases Society \n– Joseline Zafack, Public Health Agency of Canada \n– Oliver Baclic, Public Health Agency of Canada \n Ex Officio \n– Robin Levis, FDA \n– Robin Wisch, FDA  Consultants \n– Edwin Asturias \n– Doug E Campos-Outcalt \n– Emily Lutterloh \n– Walt Orenstein \n– Jennifer Rosen \n– Eli Rosenberg \n CDC \n– Achal Bhatt \n– Stephanie Bialek \n– Thomas Clark \n– Kathleen Dooling \n– Brian Edlin \n– Concepcion Estivariz \n– Halle Getachew \n– Sarah Kidd \n– Janelle King \n– Elisabeth Krow-Lucal \n– M. Steve Oberste \n– Janell Routh \n– Eileen Yee \n\n    \n \n      \n                           \n                          \n         For more information, contact CDC \n1-800-CDC-INFO (232-4636) TTY: 1-888-232-6348 www.cdc.gov \nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. \nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation use. No rights are implied or extended for use in printing or \nany use by other CDC CIOs or any external audiences.", "summary": "CCCCenen enentt ttererer ers sss     f fffo ooorrr    r DiDi DiDiss sseaea eaeassssee e    e CCCCoooonnnnttt trrr roooollll     aaaannnndddd     PP PPrr rreeeevvvvenenenenttttiii iooo onnnn  NNN Naaaatttti iiio ooonn nnaaaallll    CC CCeeeennnnttt tee eerrrr    ffffoooorrrr    II IImmmmmm mmuuuunnnni iiiz zzza aaat ttti iiio ooonn nn    aaaann nndddd    RR RReeeespsp spspiii ir rrra aaattttoo oorrrryyyy    DDDDiiiisese sesea aaase sesesess ss  Adult Polio Vaccination  Sarah Kidd, MD, MPH  ACIP…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/Polio-02-Kidd-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 29}
{"title": "RSV Pediatric 01 Long 508", "content": "1\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nMaternal/Pediatric Respiratory Syncytial Virus (RSV) \nWork Group\nSarah S. Long, MD\nChair, Maternal/Pediatric RSV Work Group \nACIP General Meeting\nFebruary 23, 2023\n\n2Work group members\nACIP Members\nSarah Long (chair)\nPablo SanchezOliver Brooks\nCamille Kotton\nEx Officio Members\nRachel Zhang (FDA -CBER)\nNicholas Geagan (FDA -CBER)\nJudy Beeler (FDA -CBER)\nYodit Belew (FDA -CDER)\nPrabha Viswanathan (FDA -CDER)\nSonnie Kim (NIH -NIAID)\nApril Killikelly (Public Health Agency of Canada)\nWinnie Siu (Public Health Agency of Canada)Valerie Marshall (OIDP/OASH)\nJessica Lee (CMS/CMCS)\nTerry Dalle -Tezze (HRSA)Consultants\nCody Meissner (Dartmouth Geisel School of Medicine)Helen Chu (University of Washington)Natasha Halasa (Vanderbilt University)\nDenise Jamieson (Emory University School of Medicine)\nDaniel Feikin (World Health Organization)\nCarol Baker (University of Texas Health Science Center)\nKevin Ault (Western Michigan University)\nLiaisons\nJames McAuley (IDSA)\nPatsy Stinchfield (NFID)\nBrenna L. Hughes (ACOG)\nNicole Chaisson (AAFP)\nSean O’Leary (AAP)Jennifer Schuster (PIDS)\nMolly Howell (AIM)CDC\nKatherine Fleming -Dutra (co -lead)\nJefferson Jones (co -lead)\nMeredith McMorrow\nMila Prill\nNatalie Thornburg\nAron Hall\nIsmael Ortega -Sanchez\nTamara Pilishvili\nMelissa Coughlin\nJamison Pike\nLauren Roper\nAmber Winn\nChris Taylor\nGRADE/ EtRconsultants\nDoug Campos -Outcalt\nRebecca MorganClaire Midgley\nFiona Havers \nTami SkoffAngie Campbell\nMichael Melgar\nAmanda PayneNicole Dowling\nNoelle Molinari\nPragna Patel\nAndrea Sharma\n3Epidemiology and burden of RSV in infants\n–RSV seasonality in United States\n–Outpatient, emergency department (ED) visits, hospitalizations, and \ndeaths\nVirology and immunology of RSV\nSafety and efficacy of nirsevimab\n–Phase 3 study in infants born ≥35 weeks gestation (initial and updated results)\n1\n–Phase 2b study in infants born 29 –34 weeks gestation\n–Phase 2/3 safety and pharmacokinetic study in infants at high risk of RSV disease\n2\n1Initial results from start of trial until pause for COVID- 19 pandemic and updated \nresults that included entire sample. 2Eligible for palivizumab.Previous maternal/pediatric RSV ACIP presentations\n4Agenda: Thursday February 23, 2023\nCost effectiveness analysis for nirsevimab –\nCDC model\nCost effectiveness analysis for nirsevimab –\nComparison to manufacturer model\nEvidence to Recommendations framework for \nnirsevimab\nClinical considerations for nirsevimab\nSafety and Efficacy of RSV Bivalent PreF\nMaternal Vaccine\nWorkgroup considerationsDr. David Hutton (University of Michigan)\nDr. Ismael Ortega Sanchez (CDC)\nDr. Jefferson Jones (CDC)\nDr. Jefferson Jones (CDC)\nDr. Iona Munjal (Pfizer)\nDr. Katherine Fleming -Dutra \n(CDC)\n5", "summary": "1 Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Maternal/Pediatric Respiratory Syncytial Virus (RSV)  Work Group Sarah S. Long, MD Chair,…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/RSV-Pediatric-01-Long-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 5}
{"title": "RSV Pediatric 02 Hutton 508", "content": "Economic Analysis of \nNirsevimab in Pediatric \nPopulations\nDavid W. Hutton, PhD, MS\nAssociate Professor, Health Management and Policy, School of Public Health\nAssociate Professor of Global Public Health, School of Public Health\nAssociate Professor, Industrial and Operations Engineering, College of Engineering\nUniversity of MichiganACIP General Meeting\nFebruary 23, 2023\n\nResearch Team\nUniversity of Michigan\n•David Hutton, PhD\n•Lisa Prosser, PhD\n•Angela Rose, MPH\n•Kerra Me rcon, MSCDC\n•Jefferson Jones, MD, MPH, FAAP\n•Mila Prill , MSPH\n•Meredith McMorrow, MD, MPH, FAAP\n•Jamison Pike, PhD\n•Katherine Fleming-Dutra\n•Ismael Ortega - Sanchez, PhD\n•Fiona Havers, MD\n•Betsy Gunnels, MSPH\n7\nConflicts of interest statements\n–Authors have no known conflict of interests.\n8\nMethods: Study question\n•Determine the cost- ef fectiveness of nirsevimab by:\n•Evaluating the population burden of disease in pediatric US \npopul\nation in terms of \n•annual resource utilization \n•total cases\n•total costs \n•deaths\n•quality- adj usted life years\n•Comparing the incremental cost -ef fectiveness ratio of nirsevimab to \nno prevention.\n•Running scenario analyses outcomes that explore key areas of \nunc\nertainty.\n•Perspective: Societal\n9\nMethods: Intervention(s)\n•Target population: US pediatric < 7 months of age entering their \nf\nirst RSV season\n•Secondary analysis high-r isk infants in their second RSV season (7 -18 \nmonths old)\n•Interventions:\n1.No n irsevimab (Natural history)\n2.Nirsevimab against RSV illness\n•Time horizon: 1 RSV season\n•Analytic horizon: lifetime\n•Discount rate: 3%\n10\nMethods: Decision Tree Model\n11No \nProphylaxis\nNirsevimabInfection Hospitalization\nED\nNone of the aboveOutpatientAlive\nDeadInfection\nAdverse \nEventsSystemic Reaction\nInjection Site Reaction\nNone of the aboveSerious Adverse EventInfection Infection\nMethods: Epidemiology\nHospitalization\n12Base Case Range Source\nRespiratory syncytial virus (RSV) \nincidence, per 100,000 See Above See AboveCDC NVSN, \nDecember 2016 to September 2020\nProportion with LRTI\nAge 0-5 months 1.0 0.5-1.0 Rainisch, 2020\nAge 6-11 months 1.0 0.5-1.0 Rainisch, 2020\nCDC New Vaccine Surveillance Network (NVSN) hospitalization rates for children under 2 years of age from December 2016 to Septem ber 2020 - 1,000 2,000 3,000 4,000\n0246810121416182022Hospitalization \nrate  per 100,000 \nchildren\nAge in months\nMethods: Epidemiology\nED and Outpatient\n13Respiratory syncytial virus \n(RSV) incidence, per 100,000 Base CaseRange Source\nEmergency Department\nAge 0 -5 months 7,500 5,500 –7,500 Lively 2019 (base case and range)\n5, \nHall 2009 (range)6\nAge 6 -11 months 5,800 5,700 –5,800\nAge 12 -23 months 3,200 3,200 –5,300 Hall 2009 (base case and range)6, \nLively 2019 (range)5\nProportion with LRTI\nAge 0 -5 months 0.65 0.25- 1.0 Rainisch, 20204\nAge 6 -11 months 0.5 0.25- 1.0 Rainisch, 20204\nMedically attended outpatient\nAge 0 -5 months21,60013,200 –\n21,600Lively 2019 (base case and range)\n5, \nHall 2009 (range)6\nAge 6 -11 months24,60017,700 –\n24,600\nAge 12 -23 months18,4406,600 –29,620 Jackson 2021 (base case and \nrange)7, Hall 2009 (range)6\nProportion with LRTI\nAge 0 -5 months 0.65 0.25- 1.0 Rainisch, 20204\nAge 6 -11 months 0.3 0.1-1.0 Rainisch, 20204\nMethods: Epidemiology\nMortality\n14Base \nCaseRange Source\nRSV mortality per hospitalization\nAge 0-5 months 0.04% 0.03-0.05% Doucette 2016\n8\nAge 6-11 months 0.04% 0.03-0.05%\nAge 12 -23 months 0.3% 0.24% -\n0.28%Gupta 201610\nSeasonality\n150.0%5.0%10.0%15.0%20.0%25.0%30.0%\nAprMay Jun JulAug Sep OctNov Dec Jan Feb MarFraction of Annual Infections\nSource: National Respiratory and Enteric Virus Surveillance System (NREVSS) (2015- 2019)\n0.00%10.00%20.00%30.00%40.00%50.00%60.00%70.00%80.00%90.00%100.00%\n0 2 4 6 8 10 12 14Efficacy\nMonthMethods: Inputs\naverage 5-month efficacy \n= trial efficacy \nSigmoid decay to \nfinal efficacy\n16Zero efficacy\nMethods: Efficacy\n17Variable Base \ncase \nvalueRange for \nsensitivity \nanalysisSource\nNirsevimab\nInitial efficacy \n(months 1- 5) against \nRSV-associated \nLRTI 80.0% 68.5% -86.1%MELODY trial \nand Phase 2b recommended dose\nEfficacy months 6-\n10 25.0% 0.0% -50.0%\nEfficacy after 10 months\n0.0%\nMethods: Provision of Nirsevimab\n•Base case:\n–At birth for those born \n•October 1 – M arch 31\n–October for those born in \n•April (~6 -m onth visit)\n•June (~4- m onth visit)\n•August (~2- m onth visit)\n–November for those born in\n•May (~6 -m onth visit)\n•July (~4- m onth visit)\n•September (~2- m onth visit)\n18\nMethods: Medical Costs\nVariable Value Range Source\nDisease-specific \nhospitalization costs \n(per hospitalization) \nAge 0-11 months $11,487 11042 -11933\nBowser 2022Age 12- 23 months $11,469 11029 -11910\nDisease-specific ED \ncosts (per ED visit)$563 544 –581 Bowser 2022\nDisease-specific outpatient costs (per \noutpatient visit)$82 46-118 Bowser 2022\n19•Bowser, 2022 is a systematic review using studies from 2014-2021\n•Funded by Sanofi\n•All numbers updated to 2022 dollars using GDP Deflator\nMethods: Productivity Costs\nVariable Value Range Source\nProductivity burden of \nRSV Disease (caregiver \nlosses)\nDays of lost productivity\nOutpatient* 2.5 0-5Fragaszy, 2018; Petrie, 2016; \nVan Wormer, 2017\nED* 2.5 0-5Fragaszy, 2018; Petrie, 2016; Van Wormer, 2017\nHospitalization^ 7.4 0-14\nLifetime productivity for those <1 year old (lost \nfrom death)1,795,936 Grosse, 2019\n20*Productivity for outpatient and ED based on adult influenza\n^Hospitalization productivity loss = length of hospitalization + 2 days\nMethods: Intervention Cost\nVariable Value Range Source\nImmunization-related \ncosts\nNirsevimab, per dose $300 $50-$600 Assumption\n21\nMethods: RSV \nHealth-Related Quality-of -Life\n22LRTI quality adjusted life DAYS lost Base Lower (Regnier) Upper (JIVE)\nOutpatient: Child 3.1 1.8 16.6\nOutpatient: Caregiver 1.5 0 9.1\nED: Child 4.9 2.9 16.6\nED: Caregiver 2.5 0 9.1\nHospitalized: Child 6.2 3.7 26.5\nHospitalized: Caregiver 2.4 0 13.6Measured in \nDays Lost\nMost \nLikely\nMethods: Additional Inputs\n•Also included nirs evimab adverse events\n–Systemic reactions\n–Injection site reactions\n–Serious adverse events\n–Medical costs\n–Productivity costs\n–Quality-adjust ed life- years lost\n23\nMethods: Uncertainty analyses\n•One- w ay sensitivity\n•Scenarios:\n–Upper respiratory infection effect \n–Timing of administration\n•Additional Scenario:\n–High-ri sk children entering the second RSV season\n24\nResults: Base Case\n25•Base Case:\n–Population of 1,000 births\n–100% uptake in the nirsevimab group\n–First RSV season\n–$300/dose\n–Nirsevimab only impacts LRTI\nResults: Health Outcomes\n26\nCohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group231 \n172 \n67 46 \n13 5  - 50 100 150 200 250\nNatural History\nNirsevimab\nNatural History\nNirsevimab\nNatural History\nNirsevimab\nMedically attended\noutpatientEmergency\nDepartmentInpatient\nURTI LRTI\nResults: Health Outcomes\n27\nCohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group59\n20.9 \n7.8 \n1.7 42.3 \n5.2 \n010203040506070\nOutpatient ED Inpatient ICU Inpatient Day ICU DayEvents Averted per 1000 births\nResults: Health Outcomes\n28\nCohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group17 48 128 581 \n24 194 \n - 100 200 300 400 500 600 700\nOutpatient ED Inpatient ICU Inpatient Day ICU DayNumber needed to Prophylax to avoid\nResults: Costs\n29\nBase cost of $300/doseCohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group $- $100,000 $200,000 $300,000 $400,000 $500,000 $600,000\nNatural History\nNirsevimab\nNatural History\nNirsevimab\nNatural History\nNirsevimab\nNatural History\nNirsevimab\nNatural History\nNirsevimab\nNatural History\nNirsevimab\nIntervention Outpatient ED Inpatient Deaths Total\nMedical Productivity\nResults: Health Outcomes\n30\nBase cost of $300/doseCohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group$2,476 $6,950 $18,515 $84,158 \n$3,429 $28,053 \n $- $10,000 $20,000 $30,000 $40,000 $50,000 $60,000 $70,000 $80,000 $90,000\nOutpatient ED Inpatient ICU Inpatient Day ICU DayCost per Event Averted\nResults: QALYs Lost\n31Adverse \nEventsOutpatient ED Inpatient Deaths Total Grand\nChild Caregiver Child Caregiver Child Caregiver Child Child Caregiver Total\nNatural \nHistory 1.95 0.98 0.90 0.45 0.22 0.09 0.15 3.22 1.51 4.73 \nNirsevimab 0.03 1.46 0.73 0.62 0.31 0.09 0.03 0.06 2.25 1.07 3.32 \nCohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group\nResults: Cost-Effectiveness\n32Overall Costs QALYsICER \n($/QALY)\nNatural \nHistory $ 357,151 4.73 \nNirsevimab $ 502,077 3.32 $ 102,805 \nBase cost of $300/doseCohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group\nSensitivity: Tornado\n33\nBase cost of $300/doseCohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group Cost QALYs Efficacy$0 $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000\nNirsevimab cost/dose\nInitial Efficacy\nProportion of Outpatient visits (age 0-5 months) with an LRTI\ndiagnosis\nProportion of hospitalizations (age 0-5 months) with an LRTI\ndiagnosis\nProportion of ED Visits (age 0-5 months) with an LRTI\ndiagnosis\nProportion of outpatient visits (age 6-11 months) with an LRTI\ndiagnosis\nRSV child QALYs lost due to outpatient visit\nRSV caregiver QALYs lost due to outpatient visit\nRSV child QALYs lost due to ED visit\nRSV caregiver QALYs lost due to ED visitIncremental Cost-Effectiveness Ratio ($/QALY)\nLow High\n $- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000\n$0 $100 $200 $300 $400 $500 $600ICER ($/QALY)\nTotal Cost of Nirsevimab (drug + administration)Sensitivity: Cost\n34 Cohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group\nScenario: Upper Respiratory Infection Effect\n35Cohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group57\n20.4\n7.7\n1.741.4\n5.1108\n33.5\n7.7\n1.741.4\n5.1\n020406080100120\nOutpatient ED Inpatient ICU Inpatient Day ICU DayEvents Averted per 1000 birthsEvents Averted\nAverted Base Averted URTIOnly Outpatient and ED \nare impacted by upper respiratory impact\n $- $20,000 $40,000 $60,000 $80,000 $100,000 $120,000 $140,000\n$0 $100 $200 $300 $400 $500 $600ICER ($/QALY)\nTotal Cost of Nirsevimab (drug + administration)Scenario: Upper Respiratory Infection Effect\n36 Cohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group\nNirsevimab is assumed to be equally efficacious in preventing upper respiratory tract infections as lower respiratory tract infections.\nScenario: Timing Analysis\n37•Cost-effectiveness of an infant receiving nirsevimab as a \nnewborn in \n– Oct- Feb\n– Oct- March\n– Oct- April\n•With varying efficacy in months 6- 10\n–0%\n–25%\n–50%\nCohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group\n38Scenario: Timing and Efficacy in \nmonths 6 -10\nSlightly Lower ICERs for Oct -MarBase cost of $300/doseCohort:1,000 nirsevimab and 1,000 \nnatural history, assuming 100% uptake in nirsevimab group $- $20,000 $40,000 $60,000 $80,000 $100,000 $120,000\n0% efficacy 25% efficacy 50% efficacyICER ($/QALY)\nOct-Feb Oct-Mar Oct-Apr\nScenario: Reduction in Palivizumab\n39Overall Costs QALYsICER \n($/QALY)\nNatural \nHistory $  418,551 4.73 \nNirsevimab $  502,077 3.32 $  59,250 \nBase cost of $300/doseCohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group•Potential cost impact if clinicians choose to use n irsevimab in \npalivizumab -eligible infants\n•Savings assumptions:\n–1.6% are high-risk (palivizumab-eligible)\n–75% uptake in high-risk\n–4.1 palivizumab doses/person on average\n–$1,228/palivizumab dose\nHigher -risk children entering the second \nRSV season\n40•Immunization in October (under 19 months old in \nOctober)\n•Incidence of RSV -associated hospitalization and mortality \nper hospitalization: \n–1x, 2x, 4x 6x, 10x higher\n•Cost\n–$600 nirsevimab costs (2x $300/dose)\n–$1000 nirsevimab costs (2x $500/dose)\nCohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group\nSecond Season, High -Risk \n41\nCohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab group020406080100\nInpatient ICU Inpatient Days ICU DaysEvents Averted per 1000 \nChildrenEvents Averted\nBase 2x 4x 6x 10x\nSecond Season, High -Risk \n42\nCost is per overall course, for 2 dosesCohort:1,000 nirsevimab and 1,000 natural history, assuming 100% uptake in nirsevimab groupICER by cost of nirsevimab\n(product plus administration) ($/QALY)\nHospitalization and \nMortality rate$600 $1000\n1x (base) $     815,051 $     1,410,155 \n2x $     449,238 $        800,666 \n4x $     145,014 $        282,945 \n6x $       53,061 $        122,409 \n10x $            404 $          27,390 \nLimitations\n•Model Structure\n–No risk groups\n–No dynamic transmission. No impact of the vaccine on transmission and \nin\ndirect effects\n•Uncertain inputs\n–Nirsevimab co st \n–QALYs lost \n–Upper respiratory tract infections\n–Palivizumab utilization\n43\nSummary\n•Nirsevimab m ay be cost -effective\n•Results sensitive to:\n–Cost per dose (Cost -S aving –316,000 $/QALY)\n–Efficacy (75,000 -153,000 $/QA LY)\n•URTI/LRTI \n–Proportion of infections with LRTI\n–Or efficacy of ni rsevimab against URTI\n–QALYs lost (41,000 -125,000 $/QA LY)\n•Hospitalization, Outpatient, ED\n•Child, Parent\n44URTI: Upper Respiratory Tract Infection\nLRTI: Lower Respiratory Tract InfectionQALY: Quality -Adjusted Life -Year\nThank You\n•Please send comments to:\n•dwhutton@umich.edu\n45", "summary": "Economic Analysis of  Nirsevimab in Pediatric  Populations David W. Hutton, PhD, MS Associate Professor, Health Management and Policy, School of Public Health Associate Professor of Global Public Health, School of Public Health Associate Professor, Industrial and Operations Engineering, College of Engineering University of MichiganACIP General Meeting February 23, 2023  Research Team University of Michigan •David Hutton, PhD •Lisa Prosser, PhD •Angela Rose, MPH •Kerra Me rcon, MSCDC •Jefferson…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/RSV-Pediatric-02-Hutton-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 40}
{"title": "RSV Pediatric 03 Sanchez 508", "content": "Economics of Preventing Respiratory Syncytial \nVirus Lower Respiratory Tract Infections (RSV-\nLRTI) among US Infants with Nirsevimab \nA SUMMARY REPORT COMPARING MODELS FROM:\nSanofi AND University of Michigan and CDC\nIsmael R. Ortega -Sanchez, PhD\nNCIRD/CDC\nACIP Meeting, February 23, 2023 \n46Disclaimer : The findings and conclusions in this report are those of the authors and do not necessarily represent the views of \nthe Centers for Disease Control and Prevention. \nNational Center for Immunization & Respiratory Diseases\nConflict of interest\n•Sanofi model :  Alexia Kieffer et al., [complete authors list and \naffiliations, upon request ]\n•Sanofi manufactures nirsevimab\n•Evidera (San Francisco, London) was funded by Sanofi\n•UM-CDC model: David W Hutton et al. from Univ Michigan, …, \nI\nsmael R Ortega -Sanchez et al. from CDC [complete authors list and \naffiliations, upon request ]\n•All authors: No conflicts of interest\n47\nOverview\nPolicy questions:\n•Should one dose of nir sevimab be recommended \n•a) at birth for all infants born during October to March a nd\n•b) for all infants born during April through September and <8 \nm\nonths of age when entering first RSV season?\n•Should nirsevimab be recommended for children <20 months of age en\ntering their second RSV season who remain at increased risk of \nsevere disease?\n48\nEconomic analysis\nQuestion: Is the use of nirsevimab against RSV LRTI in all infants <8 months \nentering their first RSV season or born during season (and in high- risk children \n<20 months entering the 2ndseason) cost-effective ?\nComparator Intervention\nBase -case\n scenario: What is the incremental cost -effectiveness of using nirsevimab in all \ninfants <8 months entering their first RSV season or born during season (and in high- risk \nchildren <20 months entering second season) relative to “Standard of Care”?\n49Standard of care (SoC)\nInfants in first season(and high-risk in 2\nnd\nseason)Giving nirsevimab to\ninf\nants in first season\n(and hi\ngh-risk in 2nd\nseason)\nStandard of Care (SoC) = Palivizumab only for infants eligible as per AAP recommendations, and no immunization for all other pr e-term \nand term infants\nFocus on key features for model comparison\n•Modeling approach\n•Targeted population(s)\n•Perspective (healthcare vs. societal)\n•Intervention strategies and comparators\n•Inputs for RSV disease burden, nirsevimab efficacy, and costs\n•Incidence of RSV disease, rates of outcomes \n•Direct and indirect costs of RSV disease\n•Intervention: efficacy, duration of protection, safety and program costs\n•Assumptions\n•Strong, influential assumptions\n50\n51Modeling design and assumptions\nSanofi UM-CDC\nStatic analytical decision -making models ✔ ✔\nSensitivity analyses (and probabilistic simulation) ✔(✔) ✔\nHypothetical population: All infants < 8 months (high risk children 8-19 \nmonths)✔(✔) ✔(✔)\nTime Frame: First year after a dose of nirsevimab\n(2ndseason, 2nd dose for high-risk 8 -19 months only)✔\n(✔)✔\n(✔)\nAnalytic Horizon: two years or seasons (for temporary disability) and \nLife Expectancy (for premature mortality)✔\n✔✔\n✔\nDiscount rate: 3% ✔ ✔\nYear of economic outcomes measured: 2022 ✔ ✔\nSocietal perspective (and healthcare perspective) ✔(✔) ✔(✔)\n52Inputs and main outcomes\nPrevention of:\n•MA RSV LRTI\n•RSV LRTI hospitalizations\n•RSV-associated deaths\nQALYs saved$/QALY saved\nNumber needed to\nimmunize (NNI) to avert an:•MA RSV LRTI\n•RSV LRTI hospitalization\n•RSV-associated deathSanofi UM-CDC\n✔ ✔\n✔ ✔\n✔ ✔\n✔ ✔\n✔ ✔\n✔ ✔\n✔ ✔\n✔ ✔\nHCRU = health care resource use, MA = Medically attended, LRTI= Lower respiratory tract infection, QALY= quality -adjusted life y ear\n\nSanofi model : Base case estimates for all infants <7 \nmonths in  Season 1, nirsevimab cost $500/dose & PSA\n53Summary outcomes Base-Case\n$/QALY gained $70,430\n$/RSV MA LRTI case averted $798\n$/RSV-associated LRTI  \nhospitalization averted $9,387\n$/RSV-assoc. death averted >$5.6Million\nNNI to avert an RSV-MA LRTI \ncase 5\nNNI to avert an RSV-\nassociated LRTI hospitalization 43\nNNI to avert a death 55,957\nProbabilistic sensitivity analysis (PSA)\nBase case\n\nUM-CDC: Base case estimates for all infants <8 \nmonths, Season 1, nirsevimab cost $300/dose \n54Cost per type of health outcome prevented Summary outcomes Base-Case\n$/QALY gained $102,805\n$/RSV-MA LRTI case averted $2,100\n$/RSV-associated \nLRTI hospitalization averted $18,881\n$/RSV-assoc. death averted n/r\nNNI avert an RSV -MA LRTI \ncase 14\nNNI avert an RSV -assoc. LRTI \nhospitalization 130\nNNI avert an RSV -assoc. death n/r\nAssuming 100% uptake in nirsevimab group\nn/r = not reported$2,528 $7,096 $18,881 $85,822 \n$3,496 $28,607 \n $- $10,000 $20,000 $30,000 $40,000 $50,000 $60,000 $70,000 $80,000 $90,000 $100,000\nOutpatient ED Inpatient ICU Inpatient\nDayICU DayCost per Event Averted\nSanofi and UM-CDC models comparison: \nSelected outcome ratios for nirsevimab\n55UM- CDC model\nPrice per dose $300Sanofi model\nPrice per dose $500\n$ / QALY gained\nnirsevimab Season 1, infants $102,805 $70,430\nnirsevimab Season 2, high risk infants $842,139b$823,131a\nnirsevimab Seasons 1 & 2 combined n/r $62,589\nnirsevimab vs palivizumab, Season 2 PEPc n/r dominant\n$ / hospitalization averted\nnirsevimab Season 1 $18,881 $9,387\nnirsevimab Seasons 1 & 2 combined n/r $8,316\na. Pre-t erm infants only\nb. High risk <19 months old infants (preterm + PEP) receiving a 2nddose of nirsevimab in October\nc. PEP= palivizumab eligible population  \nn/r = not reported\nUM-CDC model : One-way Sensitivity Analyses (Season 1 only)\nBase case: $102,805/QALY saved, nirsevimab cost $300/dose\n56Assuming 100% uptake in nirsevimab group$0 $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000\nNirsevimab cost/dose\nRSV QALYs lost Hospitalized RSV QALYS Lost\nInitial Efficacy\nRSV QALYs lost Outpatient Child\nProportion of RSV infections with an LRTI diagnosis Outpatient Age 0-5 months\nRSV QALYs lost Outpatient Child caregiver\nProportion of RSV infections with an LRTI diagnosis Hospitalizations Age 0-5 months\nProportion of RSV infections with an LRTI diagnosis ED Visits Age 0-5 months\nRSV QALYs lost ED  Child\nProportion of RSV infections with an LRTI diagnosis Outpatient Age 6-11 months\nLow HighNirsevimab cost/dose\nRSV QALYs lost by a child while hospitalized\nInitial vaccine efficacy\nRSV QALYs lost by an outpatient’s caregiver\nProportion of RSV infections with an LRTI diagnosis in outpatient visits (age 0 -5 months)\nRSV QALYs lost by a child as an outpatient \nProportion of RSV infections with an LRTI diagnosis in hospitalizations (age 0 -5 months) \nProportion of RSV diagnosis in an LRTI diagnosis in ED visits (age 0 -5 months)\nRSV QALYs lost by a child as ED patient \nProportion of RSV LRTI diagnosis in outpatients visits (age 6 -11 months)\nSanofi model : One-way Sensitivity Analyses (Season 1 only)\nBase case: $70,430/QALY saved, nirsevimab cost $500/dose\n57\n\nSanofi and UM-CDC models comparison: \nSelected influential inputs \n58•RSV-ho spitalization rate\nSanofi: Age and term -specific hospitalization rates reported in McLaurin (2016)a\nUM-CDC: From RSV -associated hospitalization ratesbamong children aged ≤2 years\n•Unitary medical cost of RSV hospitalization\nSanofi: Cost varies by term at birth and by whether Intensive Care Unit or Mechanical Ventilator were needed \nas reported in McLaurin (2016)b\nUM-CDC: Unit cost was a weighted average by term at birth and age as reported in Bowser (2022)c\n•RSV season & intervention period\nSanofi: MA RSV season based on Rainisch (2020)dbut intervention ends in February\nUM-CDC: RSV-season and intervention period based on CDC surveillance data (2016- 2019)c\n•Initial efficacy & waning\nSanofi: Constant first 5 months as in trials, linear decay from month 6 to month 10\nUM-CDC: Sigmoid decay up to 10 months; average residual protection in first 5 months equals constant \nefficacy from trials\na  McLaurin et al. J Perinatol. 2016;36(11):990- 996\nb  CDC unpublished data from the New Vaccine Surveillance Network (NVSN) (December 2016 to September 2020)\nc  Bowser et al., J Infect Dis. 2022 Aug 15; 226(Suppl 2): S225– S235\nd Rainisch et al. Vaccine . 2020;38(2):251- 257\n59UM-CDC Sanofi\nRisk of RSV hospitalization (Infants <12 \nmonths of age)1.30% \n(0.60% - 3.11%)a1.42% \n(0.49% - 4.37%)b\nMedical costs per RSV hospitalization$11,487\n($11,042 - $11,993)c$18,790 – $28,812\n(age -and term dependent)d\nMedical costs per RSV outpatient visit$82 \n($46 - $118)c$153 \n(no variation reported)\na Data from CDC-funded New Vaccine Surveillance Network (NVSN) (December 2016 to September 2020) (range values are the lowest and highest within the first 11 months of age)\nb Weighted average term - specific populations shares (range values are the lowest and highest within the first 11 months of age)\nc Adapted from Bowser et al., J I nfect Dis . 2022 Aug 15; 226(Suppl 2): S225– S235 (A systematic review study funded by Sanofi)\nd Costs in the base - case varied by age, term at birth and by whether Intensive Care Unit or Mechanical Ventilator were needed while hospitalized using percentages as wights;  data reported \nin McLaurin (2016)Sanofi and UM-CDC models comparison: \nDifferences in key inputs\nSanofi and UM-CDC models comparison: \nBase -case risk of RSV -related hospitalization by age\n600.00%0.50%1.00%1.50%2.00%2.50%3.00%3.50%4.00%4.50%5.00%\n0 months 1 months 2 months 3 months 4 months 5 months 6 months 7 months 8 months 9 months 10 months 11 monthsRisk of Hospitalization \nAge in monthsUM-CDC SanofiUM-CDC model: Laboratory -\nconfirmed RSV -associated \nhospitalization rates from New \nVaccine Surveillance Network (NVSN) data for children under 2 years of age (December 2016 to September 2020)\nSanofi model : Age and term-\nspecific weighted average of \nhospitalization rates in infants using reported rates in McLaurin \n(2016)\n0%5%10%15%20%25%30%35%Percent of annual cases\nMonth of seasonUM-CDC\nSanofi\n61Sanofi intervention\nUM-CDC interventionSanofi and UM-CDC models comparison: \nRSV-season and intervention* \nSanofi\nInterventionUM- CDC \nIntervention\nWiS (Within RSV \nseason). All Infants \nborn in- season\n(i.e., October 1stto \nFeb 29th)At birth, if born \nOctober 1st\nto \nMarch 31st\nWiS: All infants 0 -3 \nmonths of age at the \nstart of RSV season \n(i.e., in October)In October, if born in \nApril\nJune\nAugust\nOoS (Out of RSV \nseason): All infants \nborn OoS at the start \nof the RSV season \n(i.e., in October) In November, if born \nin \nMay\nJuly\nSeptember\n* RSV -season and Intervention period in UM- CDC model are based on NREVVS seasonality (2016 -2019). \nIntervention period in Sanofi model ends in February ( a month short from end of MA RSV season, Rainisch et al., Vaccine . 2020;38(2):251- 257. Technical appendix)\nSanofi and UM-CDC:  Initial nirsevimab efficacy \nand uptake \n62a MELODY trial and Phase 2b recommended dose\nb Assumed non- in feriority with palivizumab,  Hammitt et al.,  N Engl J Med. 2022;386(9):837- 846UM-CDC Sanofi\nInitial efficacy against MA RSV LRTI:  \nInpatient and outpatient (%)a80.0\n(68.5 –86.1)a79.0 \n(68.5 –86.1)a, b\n0%20%40%60%80%100%\n0 2 4 6 8 10 12Efficacy\nMonths after immunizationSanofi and UM-CDC: Assumption on duration \nof nirsevimab\n63SanofiInitial efficacy against MA LRTI = A constant \nprotection over 5 months, Then, a linear decay of efficacy from month 6 to month 10\nNo residual protection after 10 months\nUM-CDCInitial efficacy against LRTI = Average 5 months \nefficacy equals to trial estimatesSigmoid decay up to 10 months and then 0% afterwards; \nCalibrated such that the first 5 months efficacy \nequals trial estimates\n\nUM-CDC model: comparison of base case & \nselected scenarios\n64a    Base -c ase nirsevimab cost $300 per dose, immunization is for only the 1st  season  \nb \n  LRTI=Lower respiratory tract infection,  URTI= Upper respiratory tract infection\nc    Cost per QALY saved estimated by varying nirsevimab cost per dose from $200 (low) to $500 (high), immunization is for on ly th e \n1stseason Scenario UM-CDC\nNirsevimab cost per $500/dose (1stseason )c$244,677\nIntervention period October to February $107,963\nBase case a(Nirsevimab cost $300/dose, 1stseason) $102,805\nPrevention of All MA RSV visits (LRTI and URTI)b$45,092\nNirsevimab cost per $200/dose (1stseason )c$31,869\nLimitations\n65•Factors not considered that may result in overestimating the ICER \n(underestimating the cost- effectiveness) of nirsevimab immunization\n•In base -case: both models assumed \n•No protection against URTI \n•No protection against asymptomatic/unattended LRTI \n•Neither model included RSV- related costs incurred after discharge from an \nRSV-associated hospitalization or emergency department visit: \n•Productivity losses incurred by caregivers after discharge\n•Both models assumed no indirect effects of nirsevimab immunization (i.e., no protection against RSV transmission)\nConclusion\n66•Differences in key inputs among Sanofi and UM-CDC models explain differences in results:\n•Nirsevimab cost per dose\n•Seasonality and intervention period\n•Duration of nirservimab efficacy\n•Hospitalization rates\n•Medical costs\n•Base-case in both models:\n•Nirsevimab would significantly reduce RSV disease burden in infants\n•Data from clinical trials support impact estimates on disease reduction\n•Economic value of using nirsevimab in infants could be cost-effective orcostly\n•Reasonable nirsevimab price and duration of protection combined with careful design of \nseasonal interventions would determine the cost-effectiveness value of routine \nprophylaxis among infants ≤7 months of age entering their first RSV season, and those born during the RSV season\nAcknowledgements \nFrom NCIRD/CDC\n•Jamison Pike\n•Jefferson Jones\n•Meredith McMorrow\n•Mila M. Prill\n•Katherine E. Fleming -D utra\n•Michael Melgar\nAl\nso:\n•Maternal/Pediatric RSV working group members\n67\n\nEnd of Summary", "summary": "Economics of Preventing Respiratory Syncytial  Virus Lower Respiratory Tract Infections (RSV- LRTI) among US Infants with Nirsevimab  A SUMMARY REPORT COMPARING MODELS FROM: Sanofi AND University of Michigan and CDC Ismael R. Ortega -Sanchez, PhD NCIRD/CDC ACIP Meeting, February 23, 2023  46Disclaimer : The findings and conclusions in this report are those of the authors and do not necessarily represent the views of  the Centers for Disease Control and Prevention.  National Center for…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/RSV-Pediatric-03-Sanchez-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 23}
{"title": "RSV Pediatric 04 Jones 508", "content": "Centers for Disease Control and Prevention\nEvidence to Recommendations Framework: \nNirsevimab\nJefferson Jones MD MPH FAAP , CDR USPHS\nACIP General MeetingFebruary 23, 2023\nEvidence to Recommendations Framework\n71Nirsevimab is a form of passive immunization\nActive immunity results from infection or vaccination, which triggers \nanimmune response\nPassive immunity is when a person receives antibodies from an external source\n–From mother to baby through transplacental or breastmilk transfer\n–Direct administration of antibodies, such as IVIG or monoclonal antibodies \nhttps://www.cdc.gov/vaccines/vac -gen/immunity -types.htm\n72Evidence to Recommendations (EtR ) Framework\nPolicy Questions\nShould one dose of nirsevimab be recommended a) at birth for all \ninfants born during October to March and b) when entering first RSV \nseason and <8 months of age for all infants born during April through \nSeptember?\nShould one dose of nirsevimab be recommended for children <20 months of age with increased risk of severe disease entering their \nsecond RSV season?\n73Evidence to Recommendations (EtR ) Framework\nPICO Question 1\nPopulation All infants born during Apr -Sept who are <8 months of age when \nentering their first RSV season and infants born during Oct- Mar\nIntervention Nirsevimab (1 injection prior to start of RSV season or at birth if born \nduring season, 50 mg if <5 kg or 100 mg if ≥5 kg)\nComparison No nirsevimab prophylaxis\nOutcomes Medically -attended RSV- associated lower respiratory tract \ninfection (MA -LRTI)\nRSV-associated LRTI with hospitalization\nRSV-associated LRTI with ICU admission\nRSV-associated death\nAll-cause MA -LRTI\nAll-cause LRTI- associated hospitalization \nSerious adverse events\n74Evidence to Recommendations (EtR ) Framework\nEtRDomain Question(s)\nPublic Health Problem Is the problem of public health importance?\nBenefits and Harms How substantial are the desirable anticipated effects?\nHow substantial are the undesirable anticipated effects?\nDo the desirable effects outweigh the undesirable effects?\nValues Does the target population feel the desirable effects are large relative \nto the undesirable effects?\nIs there important variability in how patients value the outcome?\nAcceptability Is the intervention acceptable to key stakeholders?\nFeasibility Is the intervention feasible to implement?\nResource Use Is the intervention a reasonable and efficient allocation of resources?\nEquity What would be the impact of the intervention on health equity?\nEtRDomain: Public Health Problem\nIs RSV -associated disease among infants <8 months of age entering their \nfirst RSV season and infants born during the RSV season of public health \nimportance? \n76Changes in seasonality of RSV transmission following \nSARS -CoV2 introduction —NREVSS1, 2016 –2023\n2016- 17\n1017- 18\n2018- 19\n2019- 20\n2020- 21\n2021- 22\n2022- 23\n1Displayed results are among ~200 commercial, hospital, and \nstate/local public health laboratories which consistently report RSV \nPCR tests at an annual average of ≥10 PCR tests and ≥30 weeks of the \n12-month surveillance year. Testing is clinician -directed and results \ninclude all ages.\n77Each year among U.S. children aged less than 5 years, \nRSV is associated with…\n~1,500,0003\noutpatient visits~520,0003\nemergency department visits58,000 -80,0003,4,5\nhospitalizations100-3001,2\ndeaths\n1Thompson et al, JAMA, 2003; 2Hansen et al, JAMA Network Open, 2022; 3Hall et al, NEJM, 2009; 4Rha et al., Peds, 2020; 5McLaughlin et al, J \nInfect Dis, 2022; (*estimate 80,000 hospitalizations in infants <1y) \n78Epidemiology of RSV\nPre-pandemic RSV seasonality is well defined with limited geographic \nvariability in most of the U.S.\nRSV is the most common cause of hospitalization in U.S. infants\n–Highest hospitalization rates in first months of life\n–Risk declines by month with increasing age in infancy and early childhood\nPrematurity and other chronic diseases increase risk of RSV -associated \nhospitalization, but most hospitalizations are in healthy, term infants\n79Public Health Problem- Work Group Interpretation\nIs RSV -associated disease among infants <8 months of age entering \ntheir first RSV season and infants born during the RSV season of \npublic health importance? \nNoProbably \nNoProbably \nYesYes VariesDon’t \nknow\nEtRDomain: Benefits and Harms\nDo the desirable effects outweigh the undesirable effects?\n81Outcomes, importance, and data sources\nOutcome ImportanceaData sources\nBenefits\nMedically attended RSV LRTI Critical Phase 3 and phase 2b RCTb\nRSV LRTI with hospitalization Critical Phase 3 and phase 2b RCTb\nRSV LRTI with ICU admission Critical Phase 3 and phase 2b RCTb\nDeath due to RSV respiratory illness Critical No RSV deaths in trials\nAll-cause medically attended -LRTI Important Phase 3 and phase 2b RCTb\nAll-cause LRTI -associated hospitalization Important Phase 3 and phase 2b RCTb\nHarmsSerious Adverse Events (SAEs) Important Phase 3 and phase 2b RCT\nb\na Three options: Critical; Important but not critical; Not important for decision making\nbIncludes 3012 participants in the phase 3 trials (born >34 weeks gestational age [GA]) and 860 participants in phase 2b trial (born 29- 34 weeks GA). Among phase 2b trial \nparticipants, only those who received the recommended dose were included: infants ≥5 kg received a dose (50mg) that was deter mined to be too low to be efficacious for this \nweightLRTI: Lower respiratory tract infection, RCT: randomized control trial, ICU: intensive care unit \n82Efficacy estimates and concerns in certainty of \nassessment\nOutcome Efficacy estimate* Concerns in certainty of assessment\nBenefits\nMedically attended RSV LRTI 79.0% (95% CI: 68.5% –86.1%) Not serious (indirectness)\nRSV LRTI with hospitalization 80.6% (95% CI: 62.3% –90.1%) Not serious (indirectness)\nRSV LRTI with ICU admission 90.0% (95% CI: 16.4% –98.8%) Serious (imprecision): Too few events\nNot serious (indirectness)\nDeath due to RSV respiratory \nillnessNone recorded N/A\nAll-cause medically attended -\nLRTI34.8% (95% CI: 23.0– 44.7%) Not serious (indirectness)\nAll-cause LRTI -associated \nhospitalization44.9% (95% CI: 24.9% –59.6%) Not serious (indirectness)\n*Pooled phase 2b (excluding underdosed) and phase 3 trial estimate comparing nirsevimab arm to placebo arm\n83Efficacy estimates and concerns in certainty of \nassessment\nOutcome Efficacy estimate* Concerns in certainty of assessment\nBenefits\nMedically attended RSV LRTI 79.0% (95% CI: 68.5% –86.1%) Not serious (indirectness)\nRSV LRTI with hospitalization 80.6% (95% CI: 62.3% –90.1%) Not serious (indirectness)\nRSV LRTI with ICU admission 90.0% (95% CI: 16.4% –98.8%) Serious (imprecision): Too few events\nNot serious (indirectness)\nDeath due to RSV respiratory \nillnessNone recorded N/A\nAll-cause medically attended -\nLRTI34.8% (95% CI: 23.0– 44.7%) Not serious (indirectness)\nAll-cause LRTI -associated \nhospitalization44.9% (95% CI: 24.9% –59.6%) Not serious (indirectness)\n*Pooled phase 2b (excluding underdosed) and phase 3 trial estimate comparing nirsevimab arm to placebo arm\n84Efficacy estimates and concerns in certainty of \nassessment\nOutcome Efficacy estimate* Concerns in certainty of assessment\nBenefits\nMedically attended RSV LRTI 79.0% (95% CI: 68.5% –86.1%) Not serious (indirectness)\nRSV LRTI with hospitalization 80.6% (95% CI: 62.3% –90.1%) Not serious (indirectness)\nRSV LRTI with ICU admission 90.0% (95% CI: 16.4% –98.8%) Serious (imprecision): Too few events\nNot serious (indirectness)\nDeath due to RSV respiratory \nillnessNone recorded N/A\nAll-cause medically attended -\nLRTI34.8% (95% CI: 23.0– 44.7%) Not serious (indirectness)\nAll-cause LRTI -associated \nhospitalization44.9% (95% CI: 24.9% –59.6%) Not serious (indirectness)\n*Pooled phase 2b (excluding underdosed) and phase 3 trial estimate comparing nirsevimab arm to placebo arm\n85Relative risk of SAEs and concerns in certainty of \nassessment\nOutcome Relative risk1Concerns in certainty of assessment\nHarms\nSerious Adverse Events \n(SAEs)20.73 (95% CI: 0.59– 0.89) Serious (imprecision)\n1Pooled phase 2b and phase 3 estimate comparing nirsevimab arm to placebo arm\n2Adverse event resulting in death, hospitalization, significant disability, or requiring medical intervention. \nAdverse events include respiratory symptoms.\n86Summary of GRADE for nirsevimab\nOutcome​ Importance Design\n(# of studies)​Findings​ Level of certainty\nBenefits\nMedically attended RSV \nLRTICritical RCT (2)Nirsevimab is effective in preventing medically attended \nRSV LRTIHigh\nRSV LRTI with \nhospitalizationCritical RCT (2)Nirsevimab is effective in preventing medically attended \nRSV LRTI with hospitalizationHigh\nRSV LRTI with ICU \nadmissionCritical RCT (2)Nirsevimab is likely effective in preventing medically \nattended RSV LRTI with ICU admissionModerate\nDeath due to RSV Critical RCT (2) No deaths reported -\nAll-cause medically \nattended -LRTIImportant RCT (2)Nirsevimab is effective in preventing all cause medically \nattended LRTIHigh\nAll-cause LRTI -associated \nhospitalizationImportant RCT (2)Nirsevimab is effective in preventing all cause hospitalization with respiratory diseaseHigh\nHarms\nSerious adverse events​ Critical RCT (1)SAEs were likely not more common in intervention group \nthan placebo groupModerate\n11: High certainty; 2: Moderate certainty. 3: Low certainty; 4: Very low certainty. \n87Summary of GRADE for nirsevimab\nOutcome​ Importance Design\n(# of studies)​Findings​ Level of certainty\nBenefits\nMedically attended RSV \nLRTICritical RCT (2)Nirsevimab is effective in preventing medically attended \nRSV LRTIHigh\nRSV LRTI with \nhospitalizationCritical RCT (2)Nirsevimab is effective in preventing medically attended \nRSV LRTI with hospitalizationHigh\nRSV LRTI with ICU \nadmissionCritical RCT (2)Nirsevimab is likely effective in preventing medically \nattended RSV LRTI with ICU admissionModerate\nDeath due to RSV Critical RCT (2) No deaths reported -\nAll-cause medically \nattended -LRTIImportant RCT (2)Nirsevimab is effective in preventing all cause medically \nattended LRTIHigh\nAll-cause LRTI -associated \nhospitalizationImportant RCT (2)Nirsevimab is effective in preventing all cause hospitalization with respiratory diseaseHigh\nHarms\nSerious adverse events​ Critical RCT (1)SAEs were likely not more common in intervention group \nthan placebo groupModerate\n11: High certainty; 2: Moderate certainty. 3: Low certainty; 4: Very low certainty. \n88Summary of GRADE for nirsevimab\nOutcome​ Importance Design\n(# of studies)​Findings​ Level of certainty\nBenefits\nMedically attended RSV \nLRTICritical RCT (2)Nirsevimab is effective in preventing medically attended \nRSV LRTIHigh\nRSV LRTI with \nhospitalizationCritical RCT (2)Nirsevimab is effective in preventing medically attended \nRSV LRTI with hospitalizationHigh\nRSV LRTI with ICU \nadmissionCritical RCT (2)Nirsevimab is likely effective in preventing medically \nattended RSV LRTI with ICU admissionModerate\nDeath due to RSV Critical RCT (2) No deaths reported -\nAll-cause medically \nattended -LRTIImportant RCT (2)Nirsevimab is effective in preventing all cause medically \nattended LRTIHigh\nAll-cause LRTI -associated \nhospitalizationImportant RCT (2)Nirsevimab is effective in preventing all cause hospitalization with respiratory diseaseHigh\nHarms\nSerious adverse events​ Critical RCT (1)SAEs were likely not more common in intervention group \nthan placebo groupModerate\n11: High certainty; 2: Moderate certainty. 3: Low certainty; 4: Very low certainty. \n89Overall evidence rating\nOverall evidence rating: moderate certainty\nDowngraded based on imprecision for protection against ICU admissions \nbecause of few recorded events and imprecision of SAEs because rare \nevents are unlikely to be detected\n90Benefits and Harms\nHow substantial are the desirable anticipated effects?\n–How substantial are the anticipated effect for each main outcome \nfor which there is a desirable effect?\nMinimal Small Moderate Large Varies Don’t know\n91Benefits and Harms\nHow substantial are the undesirable anticipated effects?\n–How substantial are the anticipated effect for each main outcome \nfor which there is an undesirable effect?\nMinimal Small Moderate Large Varies Don’t know\n92Benefits and Harms\nDo the desirable effects outweigh the undesirable effects?\n–What is the balance between the desirable effects relative to the \nundesirable effects?\nFavors intervention ( Nirsevimab )\nFavors comparison (No intervention)\nFavors both\nFavors neither\nUnclear\nEtRDomain: Values\nCriterion 1: Does the target population feel that the desirable effects are \nlarge relative to undesirable effects?\nCriterion 2: Is there important uncertainty about, or variability in, how \nmuch people value the main outcomes?\n94About one-third (33%) of respondents thought their baby ‘definitely’ or \n‘probably’ would get an RSV infection within one year after being born*\nDefinitely or \nprobably would g e t  RSV\nUnsure\nDefinitely or probably would not\ng e t  RSV\n*CDC and University of Iowa/RAND survey, unpublished, of 523 people who were actively pregnant or pregnant within last \n12 months; conducted during 12/2022–1/2023; 68% of respondents had previously heard of RSV.\n95\n70% of respondents said they ‘definitely’ or ‘probably’ would get an \nRSV antibody injection for their baby if safe and effective*\n‘Definitely’ or \n‘ Probably’  would get antibody\nUnsure\n‘Definitely’  or ‘ Probably’  would not\nget antibody\n*If antibody injection was approved by FDA and recommended by CDC. CDC and University of Iowa/RAND survey, unpublished\n9663% of respondents said they were more worried or equally worried \nabout their baby experiencing side effects from an RSV antibody \ninjection vs. symptoms if sick with RSV\nWorried about \nbad side effects from antibodies\nW orried about both\nW orried about bad disease symptoms\nCDC and University of Iowa/RAND survey, unpublished\n97Parent attitudes about RSV\n38% of respondents believe that their baby would have no symptoms or \nmild symptoms if they got sick with RSV\n24% expressed uncertainty about the disease severity or treatability if their \nbaby got sick with RSV\nDespite being unsure or perceiving RSV risk to be low, respondents were \nworried their baby would need to be hospitalized if they got sick with RSV \n(mean response 4 of 5 with 5 being most worried)\nCDC and University of Iowa/RAND survey, unpublished\n98Values\nCriterion 1: Does the target population feel that the desirable effects \nare large relative to undesirable effects?\nNoProbably \nNoProbably \nYesYes VariesDon’t \nknow\n99Values\nCriterion 2: Is there important uncertainty about, or variability in, how \nmuch people value the main outcomes?\nImportant uncertainty or variability\nProbably important uncertainty or variability\nProbably not important uncertainty or \nvariability\nNo important uncertainty or variability\nNo known undesirable outcomes\nEtRDomain: Acceptability\nIs immunization with nirsevimab acceptable to key stakeholders?\n101Provider survey\nIn survey by Alliance for Patient Access and National Coalition for Infant \nHealth of 175 providers using YouGov to poll U.S. physicians\n–99% agree that parents need more information about RSV\n–86% report including RSV education as part of routine care\n–97% said immunizations could help prevent RSV\n–92% agreed that RSV immunization policy should ensure all children \nget access\nhttps://admin.allianceforpatientaccess.org/wp -content/uploads/2023/01/AfPA -and-NCfIH_The -Indirect -Impact -of-RSV_Survey -Report_Ja n-2023.pdf\n102Importance of RSV prevention recognized by relevant \nnational organizations\nAAP states that development of safe and effective RSV immunization is a \npriority\nNational Foundation for Infectious Disease roundtable agreed on the \nimportance of rapid adoption and deployment of evidence -based RSV \nprevention\n–Included National Association of County and City Health Officials\nAAP COID BGC Pediatrics 2014 Aug;134(2):415 -20. \nhttps://www.nfid.org/wp -content/uploads/2022/04/NFID -RSV-Call-to-Action.pdf\n103Acceptability\nIs immunization with nirsevimab acceptable to key stakeholders?\nNoProbably \nNoProbably \nYesYes Varies Don’t know\nEtRDomain: Feasibility\nIs nirsevimab feasible to implement among all infants <8 months of age \nentering their first RSV season and infants born during the RSV season?\n105Administration and storage\nAdministered as intramuscular injection using pre -filled, single -use syringe \navailable in the following doses for infants born during or entering 1st RSV \nseason: \n–50mg (0.5mL) for infants weighing <5 kg or \n–100mg (1.0 mL) for infants ≥5 kg\nFor high -risk infants and children entering 2ndRSV season, dosing is 200mg \n(two 100 mg doses administered at the same time\nOne dose of nirsevimab per season\nStorage at refrigerator temperatures (2 °C -8°C)\nMay be kept at room temperature (20 °C -25°C) when protected from light \nfor a maximum of 8 hours \nBeyfortus summary of product characteristics. European Medicines Agency  https://www.ema.europa.eu/en/documents/product -information/beyfortus -epar-product -information_en.pdf\n106ACIP considerations\nNirsevimab would be first passive immunization product to be \nindependently included in CDC immunization schedule\nProposed indication is for all infants and would result in population -level \nimpacts\nNirsevimab inclusion in Vaccines For Children (VFC) program undetermined\n107Considerations related to nirsevimab being classified \nas a drug\nCertain types of health care workers (e.g., medical assistants) can \nadminister vaccines but might not be able to administer a monoclonal \nantibody depending on jurisdiction\nAdverse events would be reported to FDA Adverse Event Reporting \nSystem rather than the Vaccine Adverse Event Reporting System\nBilling and administration codes for nirsevimab have not been finalized\nSome state immunization information systems might not be able to include products that are considered drugs and not vaccines\n108Feasibility\nIs immunization with nirsevimab feasible to implement among all \ninfants <8 months of age entering their first RSV season and infants \nborn during the RSV season?\nNo Probably \nNoProbably \nYesYes Varies Don’t know\nEtRDomain: Resource Use\nIs nirsevimab immunization among all infants <8 months of age entering \ntheir first RSV season and infants born during the RSV season a \nreasonable and efficient allocation of resources?\n110Cost -effectiveness results\nCost of nirsevimab per infant1 ICER ($/QALY)2\n$300 $ 102,805 \n$500 $ 244,677\nICER: Incremental cost effectiveness ratio, QALY: quality -adjusted life year\n1 Cost includes cost of administration.\n2 Restricted to lower respiratory tract infection (i.e., upper respiratory infections from RSV excluded). Incorporated costs of\noutpatient, ED, inpatient, and death from RSV LRTI. Incidence of RSV -associated outpatient, ED, and inpatient events based on \npublished and unpublished NVSN estimates. Nirsevimab efficacy based on phase 2b and phase 3 trial results. Other model \nassumptions from published literature. Cost of palivizumab not incorporated.\n111Resource Use\nIs nirsevimab immunuization among a ll infants <8 months of age \nentering their first RSV season and infants born during the RSV season a \nreasonable and efficient allocation of resources?\nAt $300 per infant\nAt $500 per infantNo Probably \nNoProbably \nYesYes Varies Don’t know\nNo Probably \nNoProbably \nYesYes Varies Don’t know\nEtRDomain: Equity\nWhat would be the impact of nirsevimab on health equity?\n113Equity and payment\nNirsevimab inclusion in Vaccines For Children (VFC) program undetermined\nIf not included in VFC, state Medicaid, Medicaid expansion (Children’s \nHealth Insurance Programs), and private insurance would likely cover \nnirsevimab\n–Underinsured and uninsured would likely have reduced access\n114Seasonal incidence per 1,000 children of RSV -associated hospitalizations \namong American Indian and Alaska Native children <5 years of age, Nov \n2019 -May 2020 ( SuNA )*\n*Hartman et al,  R SV 2022 12thInternational Symposium,  B elfast 9/29/2022- 10/2/2022; A twell et al.  (manuscript submitted,  under peer -review) SuNA = RSV Surveillance \namong Native A merican Persons\n**In cid e n ce  o f RSV -associated hosp italization in 2019 -2020 from Curns et al. (unp ub lished manuscrip t in p rep aration) included fo r comp arison. NVSN = New V accine \nSurveillance Network.Age  Chinle, Arizona   Whiteriver, \nArizona  Anchorage, Alaska  Yukon -Kuskokwim \nDelta, Alaska  NVSN** for \ncomparison  \n0-5 Months  83.0 (52.0, 132.5)  70.4 (36.3, 136.6)  35.7 (20.4, 62.6)  132.3 (98.2, 178.1)  21.6 (20.0 , 23.3)  \n6-11 Months  61.6 (35.9, 105.8)  90.1 (50.0, 162.3)  0.0 (0.0, 10.8)  91.6 (64.0, 131.0)  8.2 (7.1 , 9.3) \n0-11 Months  71.8 (50.4, 102.4)  80.6 (51.9, 125.2)  19.2 (11.2, 33.0)  112.2 (89.3, 141.0)  14.9 (13.9 , 16.0)  \n12-23 Months  42.1 (27.2, 65.3)  38.7 (22.0, 68.1)  15.6 (8.7, 27.7)  26.4 (16.6, 41.8)  4.5 (3.9 , 5.2) \n24-59 Months  10.9 (6.8, 17.4)  8.2 (4.2, 16.0)  1.1 (0.3, 3.8)  5.9 (3.2, 10.9)  1.2 (1.2 , 1.5) \n0-59 Months  27.2 (21.4, 34.4)  25.4 (18.7, 34.5)  7.7 (5.3, 11.1)  32.7 (26.9, 39.7)  4.6 (4.3, 4.8) \n \n115RSV rates of severe disease by race and ethnicity\nNational studies of death certificates found higher rates among non -\nHispanic black compared with non -Hispanic White children1\nHospitalization rates using New Vaccine Surveillance Network (NVSN) data \nhave shown mixed results2\n–Several studies have shown no differences by race or ethnicity3-5\n–Even when significant, relative risk for non -Hispanic Black and Hispanic \nchildren mildly increased (e.g., relative risk of 1.2 -2.2)5-6\n1. Hansen J Infect Dis 2022 Aug 15;226(Suppl 2):S255 -S266\n2. NVSN analyses compared incidence rates of non -Hispanic Black, non -Hispanic White, \nand Hispanic children\n3. Hall Pediatrics 2013 Aug;132(2):e341 -84. Hall NEJM 2009;360(6):588 –598\n5. Iwane Pediatrics 2004 Jun;113(6):1758 -64, findings differed by age group\n6. Rha Pediatrics 2020 Jul;146(1):e20193611, findings differed by age group\n116Equity\nWhat would be the impact of nirsevimab on health equity?\nReduced\nProbably reduced\nProbably no impact\nProbably increased\nIncreased\nVaries\nDon’t know\n117EtRSummary: All infants 1st RSV season\nEtRDomain Question(s) Work Group Judgments\nPublic Health \nProblemIs RSV -associated disease among infants <8 months of age \nentering their first RSV season and infants born during the \nRSV season of public health importance?Ye s\nBenefits and \nHarmsHow substantial are the desirable anticipated effects?\nHow substantial are the undesirable anticipated effects?\nDo the desirable effects outweigh the undesirable effects?Moderate to large\nMinimal to small\nYe s\nValues Does the target population feel the desirable effects are \nlarge relative to the undesirable effects?\nIs there important variability in how patients value the outcome?Y es/probabl y yes\nNo consensus\nAcceptability Is nirsevimab acceptable to key stakeholders? Y es/probabl y yes\nFeasibility Is the intervention feasible to implement? Probabl y yes\nResource Use Is the intervention a reasonable and efficient allocation of resources? Y es/probabl y yes \n(depends on price)\nEquity What would be in the impact of the intervention on health equity?—\n118Evidence to Recommendations Framework\nSummary: Work Group Interpretations\nAll infants 1st RSV season \nBalance of\nconsequencesUndesirable\nconsequences\nclearly\noutweigh\ndesirable\nconsequences\nin most settingsUndesirable\nconsequences\nprobably\noutweigh\ndesirable\nconsequences\nin most settingsThe balance\nbetween\ndesirable \nand undesirable\nconsequences\nisclosely\nbalanced or\nuncertainDesirable\nconsequences\nprobably\noutweigh\nundesirable\nconsequences\nin most settingsDesirable\nconsequences\nclearly\noutweigh\nundesirable\nconsequences\nin most settingsThere \nisinsufficient\nevidence \ntodetermine \nthebalance of\nconsequences\n119Evidence to Recommendations Framework\nSummary: Work Group Interpretations\nAll infants 1st RSV season \nType of\nrecommendationWe do not \nrecommend the \ninterventionWe recommend \ntheintervention for \nindividuals based on \nshared \nclinical decision -\nmakingWe recommend \ntheintervention\n2ndindication\nShould one dose of nirsevimab be recommended for children <20 months \nof age with increased risk of severe disease entering their second RSV \nseason?\n121Evidence to Recommendations (EtR ) Framework\nPICO Question\nPopulation Children age <20 months who are at increased risk of severe disease \nwith RSV and who are entering their second RSV season\nIntervention Nirsevimab (200 mg [2 x 100 mg] injection prior to start of second \nRSV season)\nComparison No nirsevimab prophylaxis\nOutcomes Medically attended RSV associated lower respiratory tract \ninfection (LRTI)\nMedically attended RSV associated LRTI with hospitalization\nMedically attended RSV associated LRTI with ICU admission\nRSV-associated death\nAll-cause MA LRTI\nAll-cause LRTI associated hospitalization\nSerious adverse events\nEtRDomain: Public Health Problem\nIs RSV disease among children who are at high risk of severe disease in \ntheir 2nd RSV season of public health importance?\nRSV-associated hospitalization rates in children aged <5 years, \nNew Vaccine Surveillance Network, 2016 -2020 \n0-5 months 6-11 months 12-23 months 24-59 months 0-59 months\n2016-2020 18.5 7.5 3.9 1.0 3.9.05.010.015.020.025.0Hospitalization Rate per 1000\n124Relative risk in 1st RSV season compared with 2nd RSV \nseason\nCDC, unpublished dataFigure:  RSV hospitalization rate ratios by age in months among children <2 years old, New Vaccine \nSurveillance Network, December 2016 through September 2020.\n6.1\n3.4\n1.9\n012345678\n0-2 vs. 12-23 3-5 vs. 12-23 6-11 vs. 12-23Rate Ratio\nComparison (age in months)\n125High- risk second season indications proposed by \nmanufacturer\nChildren up to 24 months of age who remain vulnerable to severe RSV \ndisease through their second RSV season, which may include but is not \nlimited to children with: \n– Chronic lung disease of prematurity (CLD)\n– Hemodynamically significant congenital heart disease (CHD)\n– Immunocompromised states\n– Down syndrome\n– Cystic fibrosis\n– Neuromuscular disease\n– Congenital airway anomalies\nIn MEDLEY study, palivizumab -eligible children with hemodynamically -\nsignificant CHD and CLD were included\n126Chronic conditions recommended by American Academy of Pediatrics \n(AAP) to qualify for palivizumab when entering 2ndRSV season\nGroup recommended for palivizumab\n–CLD of prematurity if require medical support (chronic corticosteroid \ntherapy, diuretic therapy, or supplemental oxygen) during the 6 -month \nperiod before the start of the second RSV season\nGroups that can be considered for palivizumab\n–Profoundly immunocompromised\n–Cystic fibrosis if manifestations of severe lung disease (previous hospitalization for pulmonary exacerbation in the first year of life or \nabnormalities on chest XR or CT that persist when stable) or weight for \nlength < 10th percentile.\nAmerican Academy of Pediatrics Committee on Infectious Diseases and Bronchiolitis Guidelines Committee. Updated guidance for palivizumab prophylaxis among \ninfants and young children at increased risk of hospitalization for respiratory syncytial virus infection. Pediatrics. 2014 A ug;134(2):415 -20. \n127WG considerations for conditions and populations to \nbe considered “high risk” \nSame children eligible for palivizumab when entering 2nd RSV season per American \nAcademy of Pediatrics recommendations\n–Children with chronic lung disease of prematurity if require medical support (chronic corticosteroid therapy, diuretic therapy, or supplemental oxygen) during the 6- month period before the start of the second RSV season\n–Children who are profoundly immunocompromised\n–Children with cystic fibrosis with manifestations of severe lung disease \n(previous hospitalization for pulmonary exacerbation in the first year of life or abnormalities on chest XR or CT that persist when stable) or weight for length < 10th percentile\nOther conditions are under review\nAmerican Academy of Pediatrics Committee on Infectious Diseases and Bronchiolitis Guidelines Committee. Updated guidance for palivizumab prophylaxis among \ninfants and young children at increased risk of hospitalization for respiratory syncytial virus infection. Pediatrics. 2014 A ug;134(2):415 -20. \n128Public Health Problem- Work Group Interpretation\nIs RSV disease among children who are at high risk of severe disease \nin their 2nd RSV season of public health importance?\nNoProbably \nNoProbably \nYesYes VariesDon’t \nknow\nEtRDomain: Benefits and Harms\nDo the desirable effects outweigh the undesirable effects?\n130MEDLEY study: Dose for children ≤24 months with \nCLD/CHD entering their second RSV season\n130\nDomachowske e t  a l. https://www.nejm.org/doi/full/10.1056/NE JMc2112186 ,  https://clinicaltrials.gov/ct2/show/NCT03959488\n\n131Outcomes, importance, and data sources\nOutcome Importancea Data sources\nBenefits\nMedically attended RSV LRTI Critical MEDLEY , Domachowske et al.\nRSV LRTI with hospitalization Critical No available data\nRSV LRTI with ICU admission Critical No available data\nDeath due to RSV respiratory illness Critical No available data\nAll-cause medically attended -LRTI Important No available data\nAll-cause LRTI -associated hospitalization Important No available data\nHarmsSerious Adverse Events (SAEs) Important MEDLEY , Domachowske et al.\na Three options: Critical; Important but not critical; Not important for decision making\n132Medically attended (MA)* RSV LRTI\nMEDLEY designed as safety and pharmacokinetics (PK) study\nNo clinical efficacy data available for children <24 months at high risk of \nsevere RSV disease entering their second RSV season\nPK data from Phase 2b, Phase 3, and MEDLEY studies (i.e., among infants \n<12 months of age) were analyzed using population modelling\nArea under the curve (AUC0-∞) was derived using individual estimates as a \nmeasure of exposure to nirsevimab\nAUC0-∞was then correlated to efficacy for prevention of the first episode of \nMA RSV LRTI in infants age <12 months from Phase 2b, Phase 3 and \nMEDLEY trials\n*Medically attended means presented for medical care, either outpatient or inpatient\n133Pharmacokinetic data for children ≤24 months with \nCLD/CHD entering their second RSV season who \nreceived 200 mg of nirsevimab\nDashed black line is the AUC Exposure -Response \nthreshold (12.8 day*mg/mL)\nNotes: black points are individual AUC predictions.\nAUC = area under the serum concentration- time curve \nderived from dose and post -hoc clearance values at \nbaseline from the final population PK model; CHD = \ncongenital heart disease; CL = clearance; CLD = chronic lung disease; GA = gestational age\nPre-determined threshold of \n80% meeting PK criteria met\nData from Sanofi/AstraZeneca\n134GRADE: medically attended RSV LRTI (n=1 study)\nMeasures of effect:\n–Pharmacokinetic extrapolation from efficacy in infants <12 months of \nage for prevention of the first MA RSV LRTI to pharmacokinetic levels in \nchildren ≤24 months with CLD/CHD entering their second RSV season\nConcerns in certainty assessment:\n–Very serious (indirectness due to surrogate outcome, outcome \nestablished in 1st season, and population that does not match proposed indication)\nEvidence type:\n–Low certainty \n135Available safety data from children ≤24 months with \nCLD/CHD entering their second RSV season who \nreceived nirsevimab (200 mg) or palivizumab (15 mg/kg)\nSubjects withCLD/CHD Cohort\nPalivizumab/ \nPalivizumab1\n(N=42)\nN (%)Palivizumab / Nirsevimab\n1\n(N=40)N (%)Nirsevimab / Nirsevimab\n1\n(N=180)N (%)\nAt least one adverse event229 (69.0) 29 (72.5) 126 (70.0)\nAt least one serious event30 ( 0.0) 4 (10.0) 17 ( 9.4)\nAt least one investigational product -related \nevent0 ( 0.0) 0 ( 0.0) 0 ( 0.0)\nAny adverse event with outcome of death 0 ( 0.0) 0 ( 0.0) 0 ( 0.0)\n1Palivizumab / Palivizumab  = Palivizumab  in season 1 / Palivizumab  in season 2; Palivizumab  / Nirsevimab  = Palivizumab  in season 1 /Nirsevimab  in season 2; \nNirsevimab  / Nirsevimab = Nirsevimab  in season 1 / Nirsevimab  in season 2\n2A ny untoward medical occurrence (e.g.,  unintended abnormal laboratory ,  symptom,  or disease temporally associated with product , whether or not considered \nassociated);3AE resulting in death, hosp italization, significant disab ility, or required medical intervention.\nData from Sanofi/A straZeneca\n136GRADE: Serious adverse events (n=1 study)\nMeasures of effect\n–Relative Risk: 8.4 (95% CI: 0.52 -135.50)1\n–Absolute risk: 176 more cases per 1,000 immunized (95% CI: 11 fewer \nto 1,000 more)\nConcerns in certainty assessment\n–Serious (indirectness because comparison group is palivizumab \nrecipients rather than placebo)\n–Very serious (imprecision)\nEvidence type:\n–Very low certainty \n1Relative risk of an serious adverse event among children who received nirsevimab in their 2nd RSV season compared with childr enwho received palivizumab their 2nd \nRSV season. Because no SAEs were reported in palivizumab group, 0.5 was added to both the nirsevimab and the palivizumab groups t o calculate relative risk.\n137Summary of GRADE for nirsevimab dose for second season\nOutcome​ Importance Design\n(# of studies)​Findings​ Level of certainty\nBenefits\nMedically attended  (MA) RSV LRTICritical 3 Nirsevimab might be effective in preventing MA RSV LRTI Low\nRSV LRTI with \nhospitalizationCriticalNo available data\nRSV LRTI with ICU \nadmissionCriticalNo available data\nRSV-associated deathCriticalNo available data\nAll cause medically attended LRTI ImportantNo available data\nAll cause hospitalization with respiratory diseaseImportantNo available data\nHarms\nSerious adverse events​ \n(SAEs)Critical 1SAEs might not be more common in intervention group \nthan placebo groupVery low137\n138Overall evidence rating\nOverall evidence rating: Very low certainty\nDowngraded based on indirectness because pharmacokinetic data used as \nsurrogate for efficacy, population did not include children that matches \nproposed indication, study small in size, and no placebo group was \nincluded for comparison\n139Benefits and harms of nirsevimab\nHow substantial are the desirable anticipated effects?\n–How substantial are the anticipated effects for each main outcome \nfor which there is a desirable effect?\nMinimal Small Moderate Large Varies Don’t know\n140Benefits and harms of nirsevimab\nHow substantial are the undesirable anticipated effects?\n–How substantial are the anticipated effect for each main outcome \nfor which there is an undesirable effect?\nMinimal Small Moderate Large Varies Don’t know\n141Benefits and harms of nirsevimab\nDo the desirable effects outweigh the undesirable effects?\n–What is the balance between the desirable effects relative to the \nundesirable effects?\nFavors intervention (Nirsevimab)\nFavors comparison (No intervention)\nFavors both\nFavors neither\nUnclear\nEtRDomains: Values, Acceptability, and \nFeasibility\n143Values\nCriterion 1: Does the target population feel that the desirable effects \nare large relative to undesirable effects?\nNoProbably \nNoProbably \nYesYes VariesDon’t \nknow\n144Values\nCriterion 2: Is there important uncertainty about, or variability in, how \nmuch people value the main outcomes?\nImportant uncertainty or variability\nProbably important uncertainty or variability\nProbably not important uncertainty or \nvariability\nNo important uncertainty or variability\nNo known undesirable outcomes\n145Acceptability\nIs RSV prevention with nirsevimab acceptable to key stakeholders?\nNo Probably \nNoProbably \nYesYes Varies Don’t know\n146Feasibility\nAdditional visit to provider might be needed for administration of \nnirsevimab prior to beginning of 2nd RSV season\nIs nirsevimab feasible to implement among high -risk children \n<20 months of age entering their second RSV season?\nNo Probably \nNoProbably \nYesYes Varies Don’t know\nEtRDomain: Resource Use\n148Resource Use\nIs nirsevimab use among a ll high-risk children aged < 20months of age \nentering their second RSV season a reasonable and efficient allocation \nof resources?\n$600 per child\n$1000 per childNo Probably \nNoProbably \nYesYes Varies Don’t know\nNo Probably \nNoProbably \nYesYes Varies Don’t know\nEtRDomain: Equity\n150Equity\nEquity issues differ by chronic condition among infants and young children\nNon -Hispanic Black populations experience higher rates of preterm birth \nthan non -Hispanic White population1\nFor children with cystic fibrosis, the majority are from non -Hispanic white \npopulations2\nHispanic populations may have higher prevalence of Down syndrome than \nnon-Hispanic White populations3\nHispanic and non -Hispanic American Indian and Alaska Native populations \nmay have higher prevalence of neuromuscular disorders than non -Hispanic \nWhite populations3\n1.https: //www.cdc.gov/reproductivehealth/maternalinfanthealth/pretermbirth.htm\n2.McGarry Pediatr Pulmonol 2021 Jun;56(6):1496- 1503\n3.Mai B irth Defects R es 2019 Nov 1;111(18):1420- 1435\n151Equity\nWhat would be the impact of nirsevimab on health equity among high -\nrisk children entering their 2ndRSV season?\nReduced\nProbably reduced\nProbably no impact\nProbably increased\nIncreased\nVaries\nDon’t know\n152Summary: Children at high risk entering 2nd RSV season\nEtRDomain Question(s) Work Group Judgments\nPublic Health \nProblemIs RSV disease among children <20 months who are at high risk of severe disease of public health importance? Yes\nBenefits and \nHarmsHow substantial are the desirable anticipated effects?\nHow substantial are the undesirable anticipated effects?\nDo the desirable effects outweigh the undesirable effects?Moderate\nMinimal\nFavors nirsevimab\nValues Does the target population feel the desirable effects are \nlarge relative to the undesirable effects?\nIs there important variability in how patients value the outcome?Probably yes\nProbably no\nAcceptability Is nirsevimab acceptable to key stakeholders? Probably yes\nFeasibility Is the intervention feasible to implement? Probably yes\nResource Use Is the intervention a reasonable and efficient allocation of \nresources?$600: Probably yes\n$1000: Probably yes or probably no\nEquity What would be in the impact of the intervention on health \nequity?-\n153Evidence to Recommendations Framework\nSummary: Work Group Interpretations\nChildren at high risk entering 2nd RSV season\nBalance of\nconsequencesUndesirable\nconsequences\nclearly\noutweigh\ndesirable\nconsequences\nin most settingsUndesirable\nconsequences\nprobably\noutweigh\ndesirable\nconsequences\nin most settingsThe balance\nbetween\ndesirable \nand undesirable\nconsequences\nisclosely\nbalanced or\nuncertainDesirable\nconsequences\nprobably\noutweigh\nundesirable\nconsequences\nin most settingsDesirable\nconsequences\nclearly\noutweigh\nundesirable\nconsequences\nin most settingsThere \nisinsufficient\nevidence \ntodetermine \nthebalance of\nconsequences\n154Evidence to Recommendations Framework\nSummary: Work Group Interpretations\nChildren at high risk entering 2nd RSV season\nType of\nrecommendationWe do not \nrecommend the \ninterventionWe recommend \ntheintervention for \nindividuals based on \nshared \nclinical decision -\nmakingWe recommend \ntheintervention\nSummary\n1561st RSV season\nThe WG recommends nirsevimab a) at birth for all infants born during \nOctober to March and b) when entering first RSV season and <8 months of age for all infants born during April through September?\nMany expressed concerns about feasibility and equity, particularly because inclusion in VFC is unknown\nSome WG expressed concern that at higher prices, nirsevimab may not be a reasonable and efficient allocation of resources\n1572nd RSV season\nWG would like more time to consider which infants and children would be \nsufficiently high risk to warrant nirsevimab in their 2ndRSV season\n–Limited efficacy and safety data\n–Limited data to measure the risk of severe disease in the 2ndRSV \nseason\n–At this time, WG recommended nirsevimab for those who are eligible for palivizumab in their 2nd RSV season, since assumed to be cost effective\n–WG will continue to evaluate other conditions\n158ACIP Policy Questions\nShould one dose of nirsevimab be recommended a) at birth for all infants \nborn during October to March and b) when entering first RSV season and \n<8 months of age for all infants born during April through September?\nShould one dose of nirsevimab be recommended for children <20 months \nof age entering their second RSV season who are eligible for palivizumab in \ntheir second RSV season?\n159Acknowledgements \nMeredith McMorrow\nLauren RoperKatherine Fleming -Dutra\nMila PrillAmanda Payne\nDanielle Moulia\nMorgan NajdowskiDavid Hutton\nJamie PikeIsmael Ortega- Sanchez\nAndrew Leidner\nSara OliverMonica Godfrey\nEvelyn Twentyman\nRebecca Morgan\nDoug Campos -Outcalt\nFor more information, contact CDC\n1-800- CDC-INFO (232- 4636)\nTTY:  1 -888- 232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.", "summary": "Centers for Disease Control and Prevention Evidence to Recommendations Framework:  Nirsevimab Jefferson Jones MD MPH FAAP , CDR USPHS ACIP General MeetingFebruary 23, 2023 Evidence to Recommendations Framework 71Nirsevimab is a form of passive immunization Active immunity results from infection or vaccination, which triggers  animmune response Passive immunity is when a person receives antibodies from an external source –From mother to baby through transplacental or breastmilk transfer…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/RSV-Pediatric-04-Jones-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 92}
{"title": "RSV Pediatric 05 Jones 508", "content": "Centers for Disease Control and Prevention\nDraft Interim Clinical Considerations: \nNirsevimab\nJefferson Jones MD MPH FAAP , CDR USPHS\nACIP General MeetingFebruary 23, 2023\n162Goals of recommendations\nProvide simple, uniform recommendations that apply to most U.S. health \ncare providers\nProvide flexibility for specific situations\n163Policy Question\nShould one dose of nirsevimab be recommended a) at birth for all \ninfants born during October to March and b) when entering first RSV \nseason and <8 months of age for all infants born during April through \nSeptember?\n164Important considerations for timing of administration\nEfficacy beyond 150 days is unknown\nMajority of infants will only be eligible for a single dose of nirsevimab\nOnly 1 dose is recommended per season\nIf nirsevimab given too early, efficacy might wane during the RSV season\nFor infants born during October –March, the optimal timing of nirsevimab\ndosing is at birth\nFor infants born during April -September, the ideal timing for nirsevimab\ndosing is just before or near the start of the RSV season\n165Timing and location of nirsevimab administration\nFor infants born during Oct–Mar, shortly after birth or as soon as possible\n–Administration in hospital prior to discharge would be optimal to \nensure early protection\n–If not given prior to discharge, administration at first visit to primary care provider, ideally within 1 week of discharge\nFor infants born Apr –Sep \n–Nirsevimab administration recommended during Oct- Nov (e.g., during \nregularly scheduled 2- , 4-, or 6- month well child visits)\n166Additional considerations\nDuring COVID-19 pandemic, interseasonal RSV transmission has \noccurred\nWork Group has expressed it is important to allow for flexibility of \ntiming in nirsevimab administration during periods of significant \ninterseasonal RSV transmission\nDuring 2023 -2024 season, nirsevimab may not be available prior to \nOctober 2023\n167RSV-associated hospitalization rates in children aged \n0-11 months, New Vaccine Surveillance Network\n0 1 2 3 4 5 6 7 8 9 10 11\n2000-2005 13.5 25.9 14.3 10.3 8.9 4.8 4.1 5.6 3.4 3.8 3.7 2.9\n2016-2020 17.6 31.1 22.3 15.6 13.6 10.9 9.6 8.0 7.3 8.4 6.0 6.00510152025303540Hospitalization rate per 1000 \nAge in months2000-2005 2016-2020\n2000 -2005: Adapted from Hall et al, Pediatrics 2013; 2016 -2020: CDC unpublished data\n168Timing of beginning nirsevimab administration\nIf increased RSV transmission is occurring locally in August or September, \nnirsevimab could be administered to eligible infants earlier than October, if available\nLocal epidemiology data may be best indicator but recommend establishing evidence -based threshold\nNational Respiratory and Enteric Virus Surveillance System (NREVSS) \n–May be used as one source of evidence\n–Census Division- level or HHS regional -level data recommended1\n–In NREVVS, >3% percent positivity of PCR tests for 2 consecutive weeks can indicate increased level of RSV detections\nhttps://www.cdc.gov/surveillance/nrevss/index.html1Data from a single state may not be representative and should be interpreted with caution\n169Timing of ending nirsevimab administration\nTo determine if nirsevimab should continue to be administered to newborns shortly \nafter birth beyond March, l ocal jurisdictions can alter administration schedules based on \nlocal transmission conditions with clear evidence of ongoing increased transmission\n–Local data may be best indicator but recommend establishing evidence -based \nthreshold\n–NREVSS\n•May be used as one source of evidence\n•Census Division- level or HHS Region- level data recommended1\n•For NREVVS data, <5% percent positivity of PCR tests for 2 consecutive weeks \ncan indicate decreasing transmission\nhttps://www.cdc.gov/surveillance/nrevss/rsv/index.html1Data from a single state may not be representative and should be interpreted with caution\n170Tropical climates\nTropical climates (e.g., Hawaii, Guam, and US -affiliated Pacific Islands) \nmay have RSV seasonality that differs from most of the continental US \nor is unpredictable\nNirsevimab administration recommended to newborns shortly after \nbirth throughout the year\nCertain jurisdictions with tropical climates (e.g., Puerto Rico) \nrecommend birth dose nirsevimab administration d uring Aug– Mar. For \ninfants born Apr -July, recommended in Aug –Sep.\nConsult with local, state, or territorial health department for \nrecommendations\n171Alaska\nIn Alaska, RSV seasonality is less predictable, and the duration of RSV \nactivity is often longer than the national average\n–Providers are advised to use RSV laboratory surveillance data generated by the state of Alaska to assist in determining the appropriate timing of \nnirsevimab\nThe Alaska Department of Health will continue to provide clinicians with \nupdated Alaska -specific guidance\n172Infants residing in remote areas\nInfants born during April– September and residing in remote areas (e.g., \nwould require medical evacuation by air for severe disease) can be \ngiven nirsevimab as early as August if there is concern that the infant \nmay not have access to nirsevimab at th e recommended time (Oct–\nNov)\n173Policy question\nShould one dose of nirsevimab be recommended for children \n<20 months of age entering their second RSV season who are eligible \nfor palivizumab in their second RSV season?\n174Population recommended for nirsevimab when \nentering 2nd RSV season\nSame groups eligible for palivizumab when entering 2nd RSV season per American \nAcademy of Pediatrics recommendations\n–Children with chronic lung disease of prematurity if require medical support (chronic corticosteroid therapy, diuretic therapy, or supplemental oxygen) during the 6- month period before the start of the second RSV season\n–Children who are profoundly immunocompromised\n–Children with cystic fibrosis with manifestations of severe lung disease \n(previous hospitalization for pulmonary exacerbation in the first year of life or abnormalities on chest XR or CT that persist when stable) or weight for length < 10th percentile\nOther conditions are under review\nAmerican Academy of Pediatrics Committee on Infectious Diseases and Bronchiolitis Guidelines Committee. Updated guidance for palivizumab prophylaxis among \ninfants and young children at increased risk of hospitalization for respiratory syncytial virus infection. Pediatrics. 2014 A ug;134(2):415 -20. \n175Timing of nirsevimab administration for 2ndRSV \nseason\nNirsevimab should be administered during October to November\nNirsevimab is not recommend to be used after the 2nd RSV season\nFor more information, contact CDC\n1-800- CDC-INFO (232- 4636)\nTTY:  1 -888- 232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.", "summary": "Centers for Disease Control and Prevention Draft Interim Clinical Considerations:  Nirsevimab Jefferson Jones MD MPH FAAP , CDR USPHS ACIP General MeetingFebruary 23, 2023 162Goals of recommendations Provide simple, uniform recommendations that apply to most U.S. health  care providers Provide flexibility for specific situations 163Policy Question Should one dose of nirsevimab be recommended a) at birth for all  infants born during October to March and b) when entering first RSV  season and…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/RSV-Pediatric-05-Jones-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 16}
{"title": "RSV Pediatric 06 Munjal 508", "content": "MedicalSafety and Efficacy of \nBivalent RSV Prefusion F Vaccine \nin Vaccinated Mothers and their Infants\nIona Munjal, MD\nSenior Director, Vaccine Research and Development \n\n178Worldwide Research, Development and Medical\nVaccine Research and DevelopmentBivalent RSV Prefusion F Vaccine \nProposed Indication:\nPrevention of lower respiratory \ntract disease and severe lower \nrespiratory tract disease caused by \nrespiratory syncytial virus (RSV)DOSE LEVEL•120 µg without an adjuvant\n•Dose contains 60 µg dose of \neach prefusion protein \nantigen, in a 0.5 mL injection\nPRESENTATION•Single dose 2 mL vial\n•1 mL Pre-filled syringe\n•Vial adaptor\nSTORAGE •Refrigeration at 2 °Cto 8°CInfants from birth through 6 months of age by active immunization of pregnant individuals\n179Worldwide Research, Development and Medical\nVaccine Research and DevelopmentGroundbreaking Structural Work by NIH Elucidated that RSV F on the \nVirus Exists as an Unstable Prefusion Form \nOnly prefusion F can bind host \ncells for RSV to infect\nAntibodies specific to the \nprefusion form are most effective \nat blocking virus infection\nMcLellan et al. Science, Nov 2013 \nPostfusion F Trimer\nfused membranePrefusion F Trimer\nAntigenic Site Ø \n(Nirsevimab, AM22) \nViral membraneAntigenic Site II\n(Synagis)\nAntigenic Site IV \n(101- F, AM14)\n\n180Worldwide Research, Development and Medical\nVaccine Research and Development2018 2019 2020 2021 2022+\nPhase 1/2\nFirst -in-Human1Adults 18- 85y\nDose Ranging\n+/-Al(OH)3 +/-Influenza\nPhase 2b2Pregnant Women 18–49y\nSafety and ImmunogenicityEarly Efficacy\nPhase 2b\n3 Nonpregnant Women 18– 49y\nConcomitant Tdap\nPhase 34 Adults 18- 49y\nLot Consistency Study\nPhase 35 Pregnant Women ≤49y\nPivotal Efficacy\n1. A Study to Describe the Safety and Immunogenicity of a RSV Vaccine in Healthy Adults. NCT03529773.\n2. A Phase 2bPlacebo- Controlled, Randomized Study of an RSV Vaccine in Pregnant Women. NCT04032093.\n3. A Study of an RSV Vaccine When Given Together with Tdap in Healthy Nonpregnant Women Aged Between 18 to 49 Years. NCT04071158.\n4. Clinical Lot Consistency for RSVpreF in a Population of Healthy Adults 18 to ≤49 Years of Age. NCT05096208.\n5. A Trial to Evaluate the Efficacy and Safety of RSVpreF in Infants Born to Women Vaccinated During Pregnancy. NCT04424316 .Pfizer’s RSVpreF Maternal Immunization Clinical Development Program\n\n181Worldwide Research, Development and Medical\nVaccine Research and Development2018 2019 2020 2021 2022+\nPhase 1/2\nFirst -in-Human1Adults 18- 85y\nDose Ranging\n+/-Al(OH)3 +/-Influenza\nPhase 2b2Pregnant Women 18–49y\nSafety and ImmunogenicityEarly Efficacy\nPhase 2b\n3 Nonpregnant Women 18- 49y\nConcomitant Tdap\nPhase 34 Adults 18- 49y \nLot Consistency Study\nPhase 35 Pregnant Women ≤49y\nPivotal Efficacy\n1. A Study to Describe the Safety and Immunogenicity of a RSV Vaccine in Healthy Adults. NCT03529773.\n2. A Phase 2bPlacebo- Controlled, Randomized Study of an RSV Vaccine in Pregnant Women. NCT04032093.\n3. A Study of an RSV Vaccine When Given Together with Tdap in Healthy Nonpregnant Women Aged Between 18 to 49 Years. NCT04071158.\n4. Clinical Lot Consistency for RSVpreF in a Population of Healthy Adults 18 to ≤49 Years of Age. NCT05096208.\n5. A Trial to Evaluate the Efficacy and Safety of RSVpreF in Infants Born to Women Vaccinated During Pregnancy. NCT04424316 .Pfizer’s RSVpreF Maternal Immunization Clinical Development Program\n\n182Worldwide Research, Development and Medical\nVaccine Research and DevelopmentRSVpreF Elicits Maternal Neutralizing Titer with GMR >12 at Delivery*\nPhase 2bCombined A/B 50% Neutralization Geometric Mean Titers & Geometric Mean Ratio vs. Placebo – in Maternal Participants at \nBaseline (24- 36 weeks GA), 1M(if Delivery had not Occurred), Delivery and Postpartum; All Evaluable (N=116 participants)\n10100100010000100000\nBaseline 1 Month Delivery 6 Months Postpartum50% Neutralizing GMT\nPlacebo 120 μ g17.8\n12.4 5.4\nLower Limit of Quantification (L LOQ), RSV A                 LLOQ , RSV B*Mean time from vaccination to delivery, 61.4 days\n183Worldwide Research, Development and Medical\nVaccine Research and DevelopmentTransplacental Transfer Ratios >1 Overall and by Geography and \nGestational Age\nCombined RSV A/B 50% Neutralization Antibody Infant v. Maternal Ratio for Phase 3 selected dose\nEvaluable Population, RSVpreF Groups (N=99)\n0.1110\nRSV A/B, All\n(n=99)Northern\nHemisphere\n(n=88)Southern\nHemisphere\n(n=11)GA 24 to <27\n(n=21)GA 27 to <30\n(n=26)GA 30 to <33\n(n=26)GA 33 to 36\n(n=26)Neutralizing Titer Transfer Ratio\nGeography Maternal Gestational Age at Vaccination\n184Worldwide Research, Development and Medical\nVaccine Research and DevelopmentRSV A/B Combined 50% Geometric Mean Neutralizing Titers by Month in Infants born to Mothers Vaccinated at 24-36 weeksInfant Neutralizing Titers Remain High Through 6 Months\n100100010000100000\n0 1 2 3 4 5 6 7RSV A/B Combined Serum Neutralizing \nTiter\nMonthsRSVpreF 120 μ g\nPlacebo\nPalivizumab reference\n---Palivizumab reference line = 50% A/B neutralizing titer of a 100ug/mL palivizumab dose, demonstrated to be efficacious in preventing infant RSV-\nassociated ICU admission (Forbes ML, Kumar VR, Yogev R, et al. Hum Vaccin Immunother 2014;10:2789 -94.)\n185Worldwide Research, Development and Medical\nVaccine Research and Development2018 2019 2020 2021 2022+\nPhase 1/2\nFirst -in-Human1Adults 18- 85y\nDose Ranging\n+/-Al(OH)3 +/-Influenza\nPhase 2b2Pregnant Women 18–49y\nSafety and ImmunogenicityEarly Efficacy\nPhase 2b\n3 Nonpregnant Women 18- 49y\nConcomitant Tdap\nPhase 34 Adults 18- 49y \nLot Consistency Study\nPhase 35 Pregnant Women ≤49y\nPivotal Efficacy\n1. A Study to Describe the Safety and Immunogenicity of a RSV Vaccine in Healthy Adults. NCT03529773.\n2. A Phase 2bPlacebo- Controlled, Randomized Study of an RSV Vaccine in Pregnant Women. NCT04032093.\n3. A Study of an RSV Vaccine When Given Together with Tdap in Healthy Nonpregnant Women Aged Between 18 to 49 Years. NCT04071158.\n4. Clinical Lot Consistency for RSVpreF in a Population of Healthy Adults 18 to ≤49 Years of Age. NCT05096208.\n5. A Trial to Evaluate the Efficacy and Safety of RSVpreF in Infants Born to Women Vaccinated During Pregnancy. NCT04424316 .Pfizer’s RSVpreF Maternal Immunization Clinical Development Program\n\n186Worldwide Research, Development and Medical\nVaccine Research and DevelopmentA Trial to Evaluate the Efficacy and Safety of RSVpreF in Infants Born to Women Vaccinated During Pregnancy. NCT04424316.MATISSE: A Phase 3 Trial to Evaluate the Efficacy and Safety of RSVpreF in \nInfants Born to Women Vaccinated During Pregnancy\n7,392 Maternal Participants in 18 Countries\nRandomized 1:1 RSVpreF 120µg or Placebo\nPregnant persons ≤49 years between \n≥24 and ≤36 weeks gestation\n7,128 Infants enrolled\n\n187Worldwide Research, Development and Medical\nVaccine Research and Development\nAEs from Consent to 28 Days\na. Screening bloods and fetal anomaly ultrasound (if not standard of care); ROW, Rest of World\nb. Fetal dating and dating ultrasounds (if not standard of care).\nc. AESI (AE of Special Interest including preterm delivery and asymptomatic SARS -CoV -2 test positive).Maternal Immunogenicity & Safety Assessment Timeline\nAESIc, SAEs : Consent to End of Study\n7 days e-diary\nScreening \nPhilippines & Africab\nScreening \nROWa\nDay -90 Day -28 Day 1 Day 7 Day 28 Variable Duration Delivery 6-Months Post Delivery\nRTI surveillance : All MA -RTI Events Captured as Endpoints from Vaccination to End of Study\nPre-Screening\nPre-vaccination \nVaccination\nVisit 1\n1-Month Follow- up\nVisit 2\nLabor & Delivery\nVisit 3\nMaternal Follow- Up\nVisit 4\n\n188Worldwide Research, Development and Medical\nVaccine Research and Development\nAEs for 28 Days\nInfant Efficacy, Immunogenicity & Safety Assessment Timeline\nAESI, SAEs and NDCMCs: Birth to End of Study\nBirth Day 1 28 Days After 6-mo 12-Mo 24-Mo\nDelivery & Infant RTI Surveillance Period* \n*Starts 72 hours after delivery\n18-Mo\nVisit 1\n Visit 2\n Visit 3\n12-Mo Follow- up \nfor All Infants \n24-mo Follow- up for Infants \nBorn in Study -year 1\nCord \nBlood\nWeekly contact with mother / \nRTI site visit + nasal swabs for MA -RTI\nMonthly contact with mother / RTI hospitalization \n& severe LRTI requires RTI visit + nasal swabs\nRTISurveillance (e-dairy)\nVisit 4\n Visit 5\n Visit 6\nAESI (AE of Special Interest including preterm birth, low birth weight, developmental delay, and asymptomatic SARS -CoV -2 test positive)\nSAE (Serious Adverse Event)\nNDCMC (Newly Diagnosed Chronic Medical Condition)\n189Worldwide Research, Development and Medical\nVaccine Research and Developmenta. N = number of participants in the specified vaccine group. This value is the denominator for the percentage calculations. \nb. n = Number of participants in the specified category. Demographic Characteristics\n(Maternal Safety Population)\nRSVpreF 120 μg\n(Na=3682) ; n (%)Placebo\n(Na=3675) ; n (%)Total\n(Na=7357) ; n (%)\nRace\nWhite 2383 (64.7) 2365 (64.4) 4748 (64.5)\nBlack or African American 720 (19.6) 723 (19.7) 1443 (19.6)\nAsian 454 (12.3) 464 (12.6) 918 (12.5)\nAmerican Indian or Alaskan Native 38 (1.0) 37 (1.0) 75 (1.0)\nNative Hawaiian or Other Pacific Islander 9 (0.2) 12 (0.3) 21 (0.3)\nMultiracial 30 (0.8) 21 (0.6) 51 (0.7)\nEthnicity\nHispanic/Latino 1049 (28.5) 1075 (29.3) 2124 (28.9)\n190Worldwide Research, Development and Medical\nVaccine Research and Development*Average GA at vaccination = 30 weeks\nNote: One participant is counted under ≥24 weeks to <28 weeks however actual age was 23 weeks 6 days. \na. N = number of participants in the specified vaccine group. This value is the denominator for the percentage calculations. \nb. n = Number of participants in the specified category. Demographic Characteristics (continued 2/2)\n(Maternal Safety Population)\nRSVpreF 120 μg\n(Na=3682) ; n (%)Placebo\n(Na=3675) ; n (%)Total\n(Na=7357) ; n (%)\nAge at Vaccination (years)\nN 3682 3675 7357\nMean (SD) 29.1 (5.64) 29.0 (5.74) 29.0 (5.69)\nMedian (Range) 29.0 (16– 45) 29.0 (14– 47) 29.0 (14– 47)\nGestational Age (GA) at Vaccination*\n≥24 weeks to <28 weeks 941 (25.6) 909 (24.7) 1850 (25.1)\n≥28 weeks to <32 weeks 1085 (29.5) 1128 (30.7) 2213 (30.1)\n≥32 weeks to ≤36 weeks 1653 (44.9) 1632 (44.4) 3285 (44.7)\n>36 weeks 3 (<0.1) 6 (0.2) 9 (0.1)\n191Worldwide Research, Development and Medical\nVaccine Research and DevelopmentDemographic Characteristics \n(Infant Safety Population)\nRSVpreF 120 μg\n(Na=3568); n (%)Placebo\n(Na=3558) ; n (%)Total\n(Na=7126) ; n (%)\nSex\nMale 1816 (50.9) 1793 (50.4) 3609 (50.6)\nFemale 1752 (49.1) 1765 (49.6) 3517 (49.4)\nRace\nWhite 2294 (64.3) 2284 (64.2) 4578 (64.2)\nBlack or African American 687 (19.3) 688 (19.3) 1375 (19.3)\nAsian 420 (11.8) 430 (12.1) 850 (11.9)\nAmerican Indian or Alaskan Native 42 (1.2) 36 (1.0) 78 (1.1)\nNative Hawaiian or other Pacific Islander 13 (0.4) 11 (0.3) 24 (0.3)\nMultiracial 65 (1.8) 59 (1.7) 124 (1.7)\nEthnicity\nHispanic/Latino 1033 (29.0) 1039 (29.2) 2072 (29.1)\na.N = number of participants in the specified vaccine group. This value is the denominator for the percentage calculations. \nb.n = Number of participants in the specified category. \n192Worldwide Research, Development and Medical\nVaccine Research and DevelopmentPhase 3 Study Objectives\nSafety•Describe the safety profile of RSVpreF\nLocal reactions and systemic events within 7 days post -vaccination\nAEs through 1-month post -vaccination (Maternal)\nAEs through 1-month after birth (Infant)\nAESIs , SAEs (Maternal and Infant) and NDCMCs (Infant) throughout study\nEfficacyPrimary•Prevention of RSV MA -LRTI within 180 days after birth \n•Prevention of RSV severe MA -LRTI within 180 days after birth\nSecondary•Prevention of RSV MA -LRTIs within 360 days after birth\n•Prevention of RSV hospitalization within 360 days after birth\n•Prevention of MA -LRTIs due to any cause within 360 days after birth\nAE, adverse event; AESI, adverse event of special interest; NDCMC, newly diagnosed chronic medical condition; SAE, serious adver se event;\nMA, medically attended; LRTI, lower respiratory tract illness; RSV, respiratory syncytial virus\n193Worldwide Research, Development and Medical\nVaccine Research and Development7.2%\n0.2%6.2%\n0.2%40.6%\n10.1%\n0102030405060708090100\nRSVpreF\n120µgPlacebo RSVpreF\n120µgPlacebo RSVpreF\n120µgPlacebo% of Subjects\nVaccine Group (as Administered)\n Mild  Moderate  SevereLocal Reactions, by Maximum Severity, within 7 Days After Vaccination\nMaternal Participants (n=7357)\nInduration/Swelling Pain at Injection Site Erythema/Redness\n194Worldwide Research, Development and Medical\nVaccine Research and Development2.6% 2.9%46.1%43.8%\n31.0%27.6%\n20.0% 19.2%26.5%\n17.1%\n11.6% 10.5%7.8% 7.0%11.2% 11.5%\n0102030405060708090100\nRSVpreF\n120µgPlacebo RSVpreF\n120µgPlacebo RSVpreF\n120µgPlacebo RSVpreF\n120µgPlacebo RSVpreF\n120µgPlacebo RSVpreF\n120µgPlacebo RSVpreF\n120µgPlacebo RSVpreF\n120µgPlacebo% of Subjects\nVaccine Group (as Administered)\nMild or 38.0°C to 38.4°C Moderate or 38.5°C to 38.9°C Severe or 39.0°C to 40.0°C >40°CSystemic Events, by Maximum Severity, Within 7 Days After Vaccination\nMaternal Participants (n=7357)\nFatigue Headache Muscle Pain Diarrhea Nausea Fever Joint Pain Vomiting\n195Worldwide Research, Development and Medical\nVaccine Research and DevelopmentAbbreviations: AESIs = adverse events of special interest; NDCMCs = newly diagnosed chronic medical conditions.\nNotes: The severity of the event is in the determination of the investigator. Per statistical analysis plan, 1 month after bi rthor 1 month after vaccination reflects a 30- day period. However, as per protocol, non- serious adverse events were only solicited\nthrough 28 days after birth/vaccination. AESIs and SAEs were solicited throughout the study for maternal participants.a. N = number of participants in the specified vaccine group. This value is the denominator for the percentage calculations. b. n = Number of participants reporting at least 1 occurrence of the specified adverse event. For \"any event\", n = number of \nparticipants reporting at least 1 occurrence of any adverse event. c. Exact 2- sided confidence interval (CI) calculated using the Clopper and Pearson method. d. An immediate AE is defined as any AE that occurred within the first 30 minutes after \nadministration of the investigational product for maternal participants.Number (%) of Participants Reporting Adverse Events by Category\nWithin 1 Month After Vaccination\nMaternal Participantsa,b,c\n13.8\n4.2\n<0.11.7 0.5 0.42.70.013.1\n3.7<0.1 1.3 0.3 0.22.50.0\n0102030405060708090100\nAny AE Serious AE Immediate AEᵈ Severe AE Life-threatening\nAERelated AESIs AE Leading to\nWithdrawalParticipants\nReporting ≥ AE %RSVpreF 120 μg\n(N=3682)\nPlacebo\n(N=3675)\n196Worldwide Research, Development and Medical\nVaccine Research and DevelopmentAbbreviations: AESIs = adverse events of special interest; NDCMCs = newly diagnosed chronic medical conditions.\nNotes: The severity of the event is in the determination of the investigator. Per statistical analysis plan, 1 month after bi rthor 1 month after vaccination reflects a 30- day period. However, as per protocol, non- serious adverse events were only solicited\nthrough 28 days after birth/vaccination. AESIs and SAEs were solicited throughout the study for maternal participants.a. N = number of participants in the specified vaccine group. This value is the denominator for the percentage calculations. b. n = Number of participants reporting at least 1 occurrence of the specified adverse event. For \"any event\", n = number of \nparticipants reporting at least 1 occurrence of any adverse event. c. Exact 2- sided confidence interval (CI) calculated using the Clopper and Pearson method. d. An immediate AE is defined as any AE that occurred within the first 30 minutes after \nadministration of the investigational product for maternal participants.Number (%) of Participants Reporting Adverse Events by Category\nWithin 1 Month After Birth\nInfant Participantsa,b,c\n37.1\n15.5\n4.51.0 <0.18.44.8\n0.2 0.034.5\n15.2\n3.81.0 0.07.2 5.9\n0.2 0.0\n0102030405060708090100\nAny AE Serious AE Severe AE Life-threatening\nAERelated AESIs Congenital\nAnomaliesNDCMCs AE Leading to\nWithdrawalParticipants\nReporting ≥ AE %RSVpreF 120 μg\n(N=3568)\nPlacebo\n(N=3558)\n197Worldwide Research, Development and Medical\nVaccine Research and DevelopmentBirth Outcomes and Developmental Delay – Infant Participants\nInfant Participants with Prematurity, Low Birth Weight, or Developmental Delay (Adverse Events of Special Interest)\n0.65.6\n0.15.1\n0.3 0.34.7\n0.24.4\n0.3\n0102030405060708090100\nEarly Premature                \n≤ 34 weeksTotal Premature              \n≤ 37 weeksVery Low Birth Weight\n< 1500gLow Birth Weight\n<2500gDevelopmental Delay% ParticipantsRSVpreF\n(N=3568)\nPlacebo(N=3558)\n198Worldwide Research, Development and Medical\nVaccine Research and DevelopmentDeaths and Fetal Losses Reported in the Trial (all unrelated)\nEvent TypeRSVpreF 120 μg\n(N=3682)Placebo\n(N=3675)\nMaternal Death: n = 1\n•1 in a maternal participant who received RSVpreF Maternal Death 1 (<0.1%) 0\nFetal Demise: n = 18\n•18 fetal demises in maternal participants who received \nVaccine/PlaceboFetal death or stillbirth 10 (0.3%) 8 (0.2%)\nEvent TypeRSVpreF 120 μg\n(N=3568)Placebo\n(N=3558)\nInfant Death: n = 17\n•16 due to various causes \n•1 infant adjudicated “Acute Respiratory Illness due to RSV” (placebo group)Infant Death 5 (0.1%) 12 (0.3%)\n199 Breakthroughs that change patients’ livesMATISSE \nInfant Efficacy Endpoints\n\n200Worldwide Research, Development and Medical\nVaccine Research and DevelopmentC3671008: https://clinicaltrials.gov/ct2/show/NCT04424316?term=C3671008&draw=2&rank=1Phase 3 Efficacy Endpoints Defined\nPrimary Endpoints Criteria\nMedically attended \nRSV LRTIMedically attended visit and ≥1 : \n•tachypnea (RR ≥60 (<2 m [60 days]) or ≥50 (≥2 to 12 m)\n•peripheral capillary oxygen saturation (SpO2) measured in room air <95% \n•chest wall indrawing\nMedically attended \nsevere RSV LRTIMedically attended visit and ≥1 : \n•tachypnea (RR ≥70 (<2 m [60 days]) or ≥60 (≥2 to 12 m)\n•SpO2 measured in room air <93%\n• high- flow nasal cannula or mechanical ventilation\n•ICU admission for >4 hours; unresponsive/unconsciousPositive \nvalidated \nRT-PCR\nin central \nlaboratoryWeekly active surveillance for ARI symptoms\nSymptoms trigger nasal swab and possibly a visit\nMedically attended visit: Infant participant taken to or seen by a healthcare provider (e.g. outpatient or inpatient visit, emer gency room, urgent care, or home visit)\nLRTI : Lower respiratory tract illness; SpO2: peripheral capillary oxygen saturation \n201Worldwide Research, Development and Medical\nVaccine Research and DevelopmentRSV-Positive MA -LRTI\nTime Interval Number of Cases (%) Number of Cases (%) Vaccine Efficacyb(%) (CI*)\n90 Days after birth 24 (0.7) 56 (1.6) 57.1 (14.7, 79.8)\n120 Days after birth 35 (1.0) 81 (2.3) 56.8 (31.2, 73.5)\n150 Days after birth 47 (1.3) 99 (2.8) 52.5 (28.7, 68.9)\n180 Days after birth 57 (1.6) 117 (3.4) 51.3 (29.4, 66.8)Maternal Vaccine Group (as Randomized)\nRSV-Positive Severe MA -LRTIRSVpreF 120 μg\n(Na=3495)Placebo\n(Na=3480)\nTime Interval Number of Cases (%) Number of Cases (%) Vaccine Efficacyb(%) (CI*)\n90 Days after birth 6 (0.2) 33 (0.9) 81.8 (40.6, 96.3)\n120 Days after birth 12 (0.3) 46 (1.3) 73.9 (45.6, 88.8)\n150 Days after birth 16 (0.5) 55 (1.6) 70.9 (44.5, 85.9)\n180 Days after birth 19 (0.5) 62 (1.8) 69.4 (44.3, 84.1)Vaccine Efficacy by Cumulative Days after Birth for Two Primary Endpoints\n*99.5% CI for 90 days, 97.58% CI for 120/150/180 days.  CI LB >20% for all time points.\nAbbreviations: RSV = respiratory syncytial virus. a. N = number of participants (at risk) in the specified group. These values a re used as the denominators for the percentage calculations. b. Vaccine efficacy was \ncalculated as 1- (P/[1- P]), where P is the number of cases in the RSVpreF group divided by the total number of cases. The confide nce interval was adjusted using Bonferroni procedure and accounting for the primary \nendpoints results.Primary Endpoints:\n202Worldwide Research, Development and Medical\nVaccine Research and DevelopmentAbbreviations: MA -LRTI = medically attended lower respiratory tract illness; RSV = respiratory syncytial virus.\na. N = number of participants (at risk) in the specified group. These values are used as the denominators for the percentage calculations.\nb. Vaccine efficacy was calculated as 1- (P/[1- P]), where P is the number of cases in the RSVpreF group divided by the total number of cases. The confidence interval was adjusted using Bonferroni procedure and accounting for the primary endpoints results.Secondary Endpoint: RSV -Positive MA-LRTIs within 360 Days After Birth\nMaternal Vaccine Group (as Randomized)\nRSVpreF 120 μg\n(Na=3495)Placebo\n(Na=3480)\nTime Interval Number of Cases (%) Number of Cases (%) Vaccine Efficacyb(%) (99.17% CI)\n210 Days after birth 70 (2.0) 127 (3.6) 44.9 (17.9, 63.5)\n240 Days after birth 76 (2.2) 133 (3.8) 42.9 (16.1, 61.6)\n270 Days after birth 82 (2.3) 137 (3.9) 40.1 (13.0, 59.2)\n360 Days after birth 92 (2.6) 156 (4.5) 41.0 (16.2, 58.9)RSV-Positive MA -LRTIs Occurring Within 360 Days After Birth Met Statistical Criteria for Success \n(CI LB>0%)\n203Worldwide Research, Development and Medical\nVaccine Research and DevelopmentMaternal Vaccine Group (as Randomized)\nRSVpreF 120 μg\n(Na=3495)Placebo\n(Na=3480)\nTime Interval Number of Cases (%) Number of Cases (%) Vaccine Efficacyb(%) (99.17% CI)\n90 Days after birth 10 (0.3) 31 (0.9) 67.7 (15.9, 89.5)\n180 Days after birth 19 (0.5) 44 (1.3) 56.8 (10.1, 80.7)\n360 Days after birth 38 (1.1) 57 (1.6) 33.3 (- 17.6, 62.9)\nAbbreviations: EAC = endpoint adjudication committee; RSV = respiratory syncytial virus.\na. N = number of participants (at risk) in the specified group. These values are used as the denominators for the percentage calculations.\nb. Vaccine efficacy was calculated as 1- (P/[1-P]), where P is the number of cases in the RSVpreF group divided by the total number of cases. The confidence interval was adjusted using Bonferroni procedure and accounting for the primary endpoints results.Secondary Endpoint: Hospitalizations Due to RSV within 360 Days \nAfter Birth\nHospitalizations Due to RSV through 180 days Met Statistical Criteria for Success (CI LB>0%)\n204Worldwide Research, Development and Medical\nVaccine Research and DevelopmentAbbreviations: EAC = endpoint adjudication committee; MA -RTI = medically attended respiratory tract illness; RSV = respiratory s yncytial virus.\na. N = number of participants (at risk) in the specified group. These values are used as the denominators for the percentage calculations.\nb. Vaccine efficacy was calculated as 1- (P/[1- P]), where P is the number of cases in the RSVpreF group divided by the total number of cases.Exploratory Endpoint: RSV -Positive MA-RTIs (EAC confirmed) within \n180 Days After Birth\nMaternal Vaccine Group (as Randomized)\nRSVpreF 120 μg\n(Na=3495)Placebo\n(Na=3480)\nTime Interval Number of Cases (%) Number of Cases (%) Vaccine Efficacyb(%) (95% CI)\n90 Days after birth 67 (1.9) 110 (3.2) 39.1 (16.7, 55.7)\n180 Days after birth 157 (4.5) 253 (7.3) 37.9 (24.0, 49.5)RSV-Positive MA -RTIs through 180 Days After Birth\n205Worldwide Research, Development and Medical\nVaccine Research and DevelopmentConsistent efficacy Was Observed Across RSV Subgroup A and B*\nRSV Severe MA -LRTI\n90, 180 Days\nRSV MA -LRTI\n90, 180 Days90 Days\n180 Days\n90 Days\n180 DaysCase Split\n(RSVpreF/Placebo) VE\n6:33 81.8%\n4:8 50.0%\n2:25 92.0%\n19:62 69.4%\n7:14 50.0%\n11:44 75.0%\nCase Split\n(RSVpreF/Placebo) VE\n24:56 57.1%\n8:12 33.3%\n17:43 60.5%\n57:117 51.3%\n19:26 26.9%\n38:87 56.3%Vaccine Efficacy (%) (95% CI)\nVaccine Efficacy (%) (95% CI)-100 -50 0 50 100RSV-BRSV-AOverallRSV-BRSV-AOverall\n \n-100 -50 0 50 100RSV-BRSV-AOverallRSV-BRSV-AOverall\n * Exploratory Endpoint –no prespecified criterion for RSV A and B\n206Worldwide Research, Development and Medical\nVaccine Research and DevelopmentRSVpreF Efficacious Against Severe Infant MA- LRTI in Phase 3 with a \nFavorable Safety Profile\nRSV = Respiratory Syncytial Virus; IA: Interim Analysis; MATISSE: MAT ernal Immunization Study for S afety and Efficacy; MA-LRTI: Medically Attended Lower Respiratory Tract Illness; CI: Confidence Interval; \nDMC: Data Monitoring Committee; BLA: Biologics License Application; FDA: Food and Drug Administration\nSource: Pfizer Press release, Oct 31, 2022Time Period Vaccine Efficacy\nFirst 90 days of life* 81.8% (CI: 40.6%, 96.3%)\nSix-month follow -up* 69.4% (CI: 44.3%, 84.1%)\nTime Period Vaccine Efficacy\nFirst 90 days of life* 57.1% (CI: 14.7%, 79.8%)\nSix-month follow -up* 51.3% (CI: 29.4%, 66.8%)Primary Endpoint: Severe MA -LRTI \nPrimary Endpoint: MA -LRTI \nRSVpreF investigational vaccine was well -tolerated with a favorable benefit -risk profile for the \nmaternal populations and their newborns.*Confidence intervals are 99.5% CI at 90 days and 97.58% CI at later intervals.\n207Worldwide Research, Development and Medical\nVaccine Research and Development•The participants and their families\n•The study investigators, nurses, coordinators, and laboratory personnel\n•Pfizer essential colleagues and our vendorsThanks to", "summary": "MedicalSafety and Efficacy of  Bivalent RSV Prefusion F Vaccine  in Vaccinated Mothers and their Infants Iona Munjal, MD Senior Director, Vaccine Research and Development   178Worldwide Research, Development and Medical Vaccine Research and DevelopmentBivalent RSV Prefusion F Vaccine  Proposed Indication: Prevention of lower respiratory  tract disease and severe lower  respiratory tract disease caused by  respiratory syncytial virus (RSV)DOSE LEVEL•120 µg without an adjuvant •Dose contains 60…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/RSV-Pediatric-06-Munjal-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 31}
{"title": "RSV Pediatric 07 Fleming Dutra 508", "content": "208\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nWork Group considerations regarding maternal RSV \nvaccine\nKatherine Fleming -Dutra, MD FAAP\nCo-lead, Maternal/Pediatric RSV Work \nGroup \nACIP General Meeting\nFebruary 23, 2023\n\n209Should the Pfizer RSV bivalent prefusion F vaccine be recommended for \nall pregnant people as a single dose given at 24 ‒36 weeks gestation?\nThis recommendation would be considered in the context of the current \nstandard of care for prevention of RSV disease in infants at the time of \nACIP vote. Policy question being considered by the work group\n210Dosing window in the trial was 24 through 36 weeks gestation\nCurrently there are no data available on efficacy stratified by gestational age at time \nof administration \nMajority of infants in phase 3 trial were born ≥37 weeks gestation (94% in RSV \nbivalent preF arm and 95% in placebo arm)\nMost doses in the phase 3 trial were given at ≥28 weeks gestation\n–25% doses given at ≥24 to <28 weeks\n–30% doses given at ≥28 to <32 weeks\n–45% doses given at ≥32 to <37 weeks\n–0.1% doses given at ≥37 weeksKey considerations regarding RSV bivalent prefusion F \nvaccine: timing of dose within pregnancy\nData provided by Pfizer\n211All pregnant people in the trial received their first and only dose of RSV \nvaccine\nCurrently there are no data available on\n–Efficacy of the first lifetime dose during subsequent pregnancies\n–Safety of additional doses given in subsequent pregnanciesKey considerations for RSV bivalent prefusion F vaccine: \nnumber of total lifetime doses \n212June 2023\n–Summary of GRADE\n–Cost effectiveness analysis\n–EtR\nOctober 2023\n–ACIP vote (if product is licensed by this time)Proposed timeline of future ACIP presentations (tentative)\n213", "summary": "208 Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Work Group considerations regarding maternal RSV  vaccine Katherine Fleming -Dutra, MD…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/RSV-Pediatric-07-Fleming-Dutra-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 6}
{"title": "RSV Adults 01 Kotton 508", "content": "Centers for Disease Control and Prevention\nAdult Respiratory Syncytial Virus (RSV) Session\nCamille Kotton, MD\nChair, Adult RSV Work Group\nAdvisory Committee on Immunization Practices (ACIP)\nFebruary 23, 2023\n2Adult RSV Work Group Membership\nACIP Voting Members\nCamille Kotton (Chair)\nKeipp Talbot\nSarah Long\nEx Officio Members\nRachel Zhang (FDA)\nJudy Beeler (FDA)\nNicholas Geagan (FDA)\nNadine Peart (FDA)Sonnie Kim (NIH/NIAID)\nJeffrey Kelman (CMS)\nValerie Marshal (OIDP)CDC Lead\nMichael Melgar\nConsultants\nRobert Atmar (Baylor College of Medicine)\nHelen Chu (University of Washington)\nMarie Griffin (Vanderbilt University Medical Center)Cynthia Lucero -Obusan (Veterans Health Administration)\nTracy Ruckwardt (NIH/NIAID)\nLiaisons\nKenneth Schmader (AGS)\nShmuel Shoham (ACP)\nGretchen LaSalle (AAFP)April Killikelly (NACI, PHAC)Winnie Su (NACI, PHAC)Michael Hogue (APhA)Katherine Williams (APTR)Ruth Lynfield (NFID)Jennifer Heath (AIM)\n3CDC Contributors\nCoronavirus and Other Respiratory \nViruses Division\nFiona Havers \nMeredith McMorrow\nDiya SurieJennifer DeCuir\nLauren Roper\nMila PrillAmanda Payne\nNatalie Thornburg\nMelissa CoughlinJefferson Jones\nKatherine Fleming-Dutra\nIsmael Ortega SanchezImmunization Safety Office\nAnne Hause\nDavid Shay\nChristine Olson\nImmunization Services Division\nNeil Murthy\nPatricia Wodi\nDebra Blog\nAndrew LeidnerJamison Pike\n4Recap of RSV session, October 2022\nManufacturer safety and efficacy presentation by GSK regarding \nadjuvanted candidate RSV vaccine for older adults: RSVpreF3\nManufacturer safety and efficacy presentation by Pfizer regarding\nbivalent candidate RSV vaccine for older adults: RSVpreF\nWork group interim considerations regarding novel RSV vaccines for older adults\n5Recent work group discussion\nCost effectiveness of RSV vaccination among U.S. older adults\nGRADE and Evidence to Recommendations for GSK adjuvanted RSVpreF3\nGRADE and Evidence to Recommendations for Pfizer bivalent RSVpreF\nCDC vaccine safety surveillance systems\n6Recent work group discussion\nPossible policy recommendations* for RSV vaccination of U.S. older adults\n–Should RSV vaccines be recommended for U.S. adults aged ≥65 years?\n–Should RSV vaccines be recommended for U.S. adults aged ≥60 years?\n*FDA has not yet completed review of safety and efficacy data for the GSK adjuvanted RSVpreF3 vaccine and the \nPfizer bivalent RSVpreF vaccine. ACIP recommendations would be made only if the vaccines are approved and \nlicensed by FDA.\n7Agenda: Thursday February 23, 2023\nCost effectiveness of RSV vaccination \na\nmong U.S. older adults\nComparison of RSV vaccination economic a\nnalyses performed by U. Michigan/CDC, \nGSK, and Pfizer\nEvidence to Recommendations framework f\nor GSK and Pfizer candidate vaccines\nDiscussion of vaccine policy optionsD\nr. David Hutton\n(U. Michigan)\nDr. Ismael Ortega Sanchez \n(CDC)\nDr. Michael Melgar (CDC)\nD r. Michael Melgar (CDC)", "summary": "Centers for Disease Control and Prevention Adult Respiratory Syncytial Virus (RSV) Session Camille Kotton, MD Chair, Adult RSV Work Group Advisory Committee on Immunization Practices (ACIP) February 23, 2023 2Adult RSV Work Group Membership ACIP Voting Members Camille Kotton (Chair) Keipp Talbot Sarah Long Ex Officio Members Rachel Zhang (FDA) Judy Beeler (FDA) Nicholas Geagan (FDA) Nadine Peart (FDA)Sonnie Kim (NIH/NIAID) Jeffrey Kelman (CMS) Valerie Marshal (OIDP)CDC Lead Michael Melgar…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/RSV-Adults-01-Kotton-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 8}
{"title": "RSV Adults 02 Hutton 508", "content": "Economic Analysis of RSV \nVaccination in Older Adults \nDavid W. Hutton, PhD, MS\nAssociate Professor, Health Management and Policy, School of Public Health\nAssociate Professor of Global Public Health, School of Public Health\nAssociate Professor, Industrial and Operations Engineering, College of Engineering\nUniversity of Michigan\n\nResearch Team\nUniversity of Michigan\n•David Hutton, PhD\n•Lisa Prosser, PhD\n•Angela Rose, MPH\n•Kerra Me rcon, MSCDC\n•Michael Me lgar, MD\n•Mila Prill , MSPH\n•Jamison Pike, PhD\n•Ismael Ortega - Sanchez, PhD\n•Fiona Havers, MD\n•Michael Whitaker, MPH\n•Christopher Taylor, PhD\n2\nConflicts of interest statements\n–No known conflict of interests.\n3\nMethods: Study question\n•Determine the cost -ef fectiveness of RSV vaccination by:\n•Evaluating the population burden of disease in the US population \n• ≥60 years old \n• ≥65 years old\n• ≥70 years old\n• ≥75 years old\n• Examining outcomes:\n•resource utilization \n•total cases\n•total costs \n•deaths\n•quality -ad justed life years\n•Comparing vaccination to no vaccination using the incremental cost -\nef\nfectiveness ratio\n•Scenario analyses exploring uncertainty.\n•Perspective: Societal\n4\nMethods: Intervention(s)\n•Target population: US adults, stratified by age\n•Interventions: GSK and Pfizer vaccines\n•Each compared to No Vaccination\n•Base case assumes the age - based RSV vaccination recommendation is \nfor ages ≥65\n•Time horizon: 1 year\n•Analytic horizon: lifetime\n•Discounting rate: 3%\n5\nMethods: Decision Tree Model\nNo \nVaccination\nVaccinationInfection Hospitalization\nED\nNone of the aboveOutpatientAlive\nDeadInfection\nAdverse \nEventsSystemic Reaction\nInjection Site Reaction\nNone of the aboveSerious Adverse EventInfection Infection\n6\nMethods: Epidemiology\n•Incidence of RSV\n–\noRaw reported incidence may be underreported because of imperfect \nPCR sensitivity\nBase case assumption: 95% sensitivity\nAdditional scenario: lower sensitivity\nZhang et al study which found decreased RSV PCR sensitivity when paired serology \ntesting was added as an additional testing method. \n7Zhang Y, Sakthivel SK, Bramley A, Jain S, Haynes A, Chappell JD, Hymas W, Lenny N, Patel A, Qi C, Ampofo K, Arnold SR, Self WH, Williams DJ, Hillyard D, \nAnderson EJ, Grijalva CG, Zhu Y, Wunderink RG, Edwards KM, Pavia AT, McCullers JA, Erdman DD. Serology Enhances Molecular Diagnosis of Respiratory Virus \nInfections Other than Influenza in Children and Adults Hospitalized with Community-Acquired Pneumonia. J Clin Microbiol . 2016 Dec 28;55(1):79-89. doi: \n10.1128/JCM.01701-16. PMID: 27795341; PMCID: PMC5228265\nMethods: Epidemiology\nHospitalization\nVariable Value Range Source\n60≤ age ≤64 years 42 29 –103\nCDC R SVnet 65≤ age ≤74 years 67 48 –203\nage ≥75 years 193 133 –575\n•CDC RSVnet data from RSV seasons: 2015- 16, 2016- 17, 2017- 18, and 2018- 19.\n•Base value is based upon the average burden adjusted rate over those four seasons.\n•“burden adjusted” means it is adjusted for a \"Standard\" PCR test sensitivity of 95%*. \n•Range lower bound is based on the lower 95% confidence limit for the base estimates\n•Range upper bound is based on the upper 95% confidence limit but also uses a different \n“burden adjustment” multiplier of 1.4x based on a reduced PCR test sensitivity **\n* Kujawski SA, Whitaker M, Ritchey MD, Reingold AL, Chai SJ, Anderson EJ, Openo KP , Monroe M, Ryan P , Bye E, Como -Sabetti K, Bar ney GR, Muse A, Bennett NM, Felsen \nCB, Thomas A, Crawford C, Talbot HK, Schaffner W, Gerber SI, Langley GE, Kim L. Rates of respiratory syncytial virus (RSV)-associated hospitalization among adults with \ncongestive heart failure- United States, 2015 -2017. PLoS One. 2022 Mar 9;17(3):e0264890. doi: 10.1371/journal.pone.0264890. PMID: 35263382; PMCID: PMC8906631.\n** Zhang Y , Sakthivel SK, Bramley A, Jain S, Haynes A, Chappell JD, Hymas W, Lenny N, Patel A, Qi C, Ampofo K, Arnold SR, Sel f WH, Williams DJ, Hillyard D, Anderson EJ, \nGrijalva CG, Zhu Y , Wunderink RG, Edwards KM, Pavia AT, McCullers JA, Erdman DD. Serology Enhances Molecular Diagnosis of Respir atory Virus Infections Other than \nInfluenza in Children and Adults Hospitalized with Community -Acquired Pneumonia. J Clin Microbiol. 2016 Dec 28;55(1):79- 89. doi: 10.1128/JCM.01701 -16. PMID: \n27795341; PMCID: PMC5228265.8RSV incidence, per 100,000 \nHospitalization\nMethods: Epidemiology\nED and Outpatient\nVariable Value Range Source\nRSV incidence, per 100,000 \nEmergency Department\n60≤ age ≤64 years 74 59 –132\nMcLaughlin 202265≤ age ≤74 years 133 0 –478\nage ≥75 years 133 0 –478\nRSV Incidence, per 100,000Outpatient\n60≤ age ≤64 years 1148 935 –2041\nMcLaughlin 2022 65≤ age ≤74 years 1519 1109 –2893\nage ≥75 years 1519 1109 –2893\n9•McLaughlin et. al. is a Pfizer- sponsored meta -analysis\n•Range upper bound is based on the upper 95% confidence limit but also uses the authors’ \nmultiplier of 1.5x to adjust for PCR sensitivity\nMcLaughlin JM, Khan F, Begier E, Swerdlow DL, Jodar L, Falsey AR. Rates of Medically Attended RSV Among US Adults: A \nSystematic Review and Meta- analysis. Open forum infectious diseases 2022 Jul (Vol. 9, No. 7, p. ofac300). \nMethods: Inputs\nVariable Value Range Source\nRSV mortality per hospitalization\n60≤ age ≤64 years 3.9% 3.12% –4.68%\nCDC RSVnet 65≤ age ≤74 years 4.3% 3.44% –5.16%\nage ≥75 years 5.7% 4.56% –6.84%\n10CDC RSVnet data includes the following RSV seasons: 2015 -16, 2016- 17, 2017- 18, and 2018- 19.\nRanges incorporate a 20% increase/reduction from the base case value\nMethods: Incidence\nSeasonality\nSource: NREVSS (2015 -19)0%5%10%15%20%25%30%\nOct Nov Dec Jan Feb Mar Apr May Jun Jul Aug SepFraction of Annual Infections\n11\nMethods: Efficacy\nVariable Value Range Source\nVaccine Efficacy (%)\nGSK\nMedically attended RSV \nLRTI/LRTD (ED, and \nhospitalization)87.5% 58.4% –96.2% GSK phase 3 trial\nMedically attended RSV ARI \n(outpatient)79.0% 54.3% –91.5% GSK phase 3 trial\nPfizer\nMedically attended RSV \nLRTI/LRTD (ED, and \nhospitalization)80.0% 6.3% –97.9% Pfizer phase 3 trial\nMedically attended RSV ARI \n(outpatient)69.2% 30.0% –88.0% Pfizer phase 3 trial\n12\n0%10%20%30%40%50%60%70%80%90%100%\n0 2 4 6 8 10 12Efficacy\nMonth\nAgainst RSV-associated ARI (outpatient) Est. Against RSV-associated ARI (outpatient)\nAgainst hospitalization and ED Est. Against hospitalization and EDEfficacy: GSK\naverage 6-month \nefficacy = trial efficacy \nExponential decay\n13\n0%10%20%30%40%50%60%70%80%90%100%\n0 2 4 6 8 10 12Efficacy\nMonth\nAgainst RSV-associated ARI (outpatient) Est. Against RSV-associated ARI (outpatient)\nAgainst hospitalization and ED Est. Against hospitalization and EDEfficacy: Pfizer\naverage 6-month \nefficacy = trial efficacy \nExponential decay\n14\nMethods: RSV Medical Costs\nVariable Value Range Source\nDisease -specific \nhospitalization costs (per \nhospitalization)\n60≤ age ≤64 years $20,330 9,288 –45,454\nAckerson 2020* 65≤ age ≤74 years $20,330 10,491 –43,619\nage ≥75 years $21,339 10,491 –43,619\nDisease -specific ED costs \n(per ED visit)\n60≤ age ≤64 years $1,210 -\n2016 Marketscan* 65≤ age ≤74 years $1,210 -\nage ≥75 years $1,210 -\nDisease -specific \noutpatient costs (per outpatient visit)\n60≤ age ≤64 years $117.58 65.88-145.38 MarketScan\nand Medicare FFS, 2020-\n202165≤ age ≤74 years $100.86 50.48-120.08\nage ≥75 years $100.86 50.48-120.08\n*Updated to Q3 2022$ using GDP Deflator15\nMethods: Vaccination-Related Costs\nVariable Value Range Source\nVaccine, per dose $100 $50-$200 Assumption\nVaccine administration $16.96 -HCPCS 90460 (Physician Fee \nSchedule 2022)\n16And productivity costs for individuals time at clinic or pharmacy\nMethods: RSV Health-Related Quality-of -Life\nVariable Value Range Source\nQALYs lost due to \nOutpatient RSV 0.0185 0.0053- 0.0347 JIVE COVID/RSV \nutilities study \n(unpublished) Hospitalized RSV 0.0193 0.0095- 0.0316\n17\nMethods: Additional Inputs\n•Also included \n–RSV illness productivity costs\n–Vaccination productivity costs\n–Vaccination adverse events\n•Systemic reactions\n•Injection site reactions\n•Serious adverse events\n•Medical costs\n•Productivity costs\n18\nMethods: Sensitivity analyses\n•Sensitivity analyses conducted\n–One-W ay and Two-Way\n–Age- b ased recommendation for RSV vaccination\n•age ≥60 years\n•age ≥65 years\n•age ≥70 years\n•age ≥75 years\n–Vaccine cost\n$50-$200\n•Scenario analysis: Higher incidence\n19\nResults: Base Case\n•Cohort of 100,000\n•20% vaccination coverage\n•Age-bas ed vaccination recommendation: ≥65 years\n•$100 vaccine cost\n•One Year Time Horizon\n20\nHealth Outcomes\n21$100 vaccine cost\nOne Year Time HorizonCohort:100,000, 20% uptakeAge-based vaccination recommendation: ≥65 years1519\n133108\n22 6649\n651280\n111 90\n18 5540\n541308\n11493\n19 5555\n56\n02004006008001000120014001600\nNo Vaccination GSK Pfizer\nNumber Needed to Vaccinate, GSK\n22One Year Time Horizon\n90 \n1,032 \n1,348 \n6,740 \n27,284 \n225 \n2,247 84 \n893 \n1,097 \n5,486 \n21,442 \n183 \n1,829 84 \n893 \n895 \n4,475 \n16,691 \n149 \n1,492 84 \n893 \n615 \n3,076 \n10,794 \n103 \n1,025 \n - 5,000 10,000 15,000 20,000 25,000 30,000 35,000 40,000 45,000Number Needed to Vaccinate\nage ≥60 years age ≥65 years age ≥70 years age ≥75 years \nNumber Needed to Vaccinate, Pfizer\n23\nOne Year Time Horizon\n103 \n1,200 \n1,567 \n7,835 \n31,717 \n261 \n2,612 95 \n1,038 \n1,275 \n6,377 \n24,927 \n213 \n2,126 95 \n1,038 \n1,040 \n5,202 \n19,404 \n173 \n1,734 95 \n1,038 \n715 \n3,576 \n12,548 \n119 \n1,192 \n - 5,000 10,000 15,000 20,000 25,000 30,000 35,000 40,000 45,000Number Needed to Vaccinate\nage ≥60 years age ≥65 years age ≥70 years age ≥75 years \nCost per Outcome Averted\n($ thousands)\n24$100 vaccine cost\nOne Year Time HorizonAge-based vaccination recommendation: ≥65 years$8 $83 $101 $507 $1,982 \n$17 $169 \n$9 $100 $123 $614 $2,402 \n$20 $205 \n $- $500 $1,000 $1,500 $2,000 $2,500 $3,000Cost per Outcome Averted\nThousandsGSK Pfizer\nSummary measure(s)\nGSK\nCosts (M) QALYs LostICER \n($/QALY) LYs LostICER \n($/LY)\nNo \nVaccination3.75 75 55\nVaccine 5.59 64 180,720 46 198,676 \n25QALY = Quality -Adjusted Life -Year\nICER = Incremental Cost -Effectiveness Ratio\nLY = Life- Year\nCost, QALY, and LY Results per 100,000 (20% of whom are vaccinated)\nCosts in Millions of 2022 dollarsICER values do not depend on cohort size or uptake$100 vaccine costOne Year Time Horizon Age-based vaccination recommendation: ≥65 years\nSummary measure(s)\nPfizer\nCosts (M) QALYs LostICER \n($/QALY) LYs LostICER \n($/LY)\nNo \nVaccination3.75 75 55\nVaccine 5.67 64 189,407 47 240,699 \n26QALY = Quality -Adjusted Life -Year\nICER = Incremental Cost -Effectiveness Ratio\nLY = Life- Year\nCost, QALY, and LY Results per 100,000 (20% of whom are vaccinated)\nCosts in Millions of 2022 dollarsICER values do not depend on cohort size or uptake$100 vaccine costOne Year Time Horizon Age-based vaccination recommendation: ≥65 years\nResults: Sensitivity analyses, \n•Tornado Diagrams \n–one parameter varied at a time\n•Age and Vaccine Cost\n•Higher Incidence / Lower PCR Sensitivity\n27\nSensitivity analyses, GSK Tornado Diagram\n28$100 vaccine cost\nOne Year Time HorizonAge-based vaccination recommendation: ≥65 years$0 $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000\nVaccine Cost\nIncidence of RSV hospitalization\nOutpatient QALYs Lost\nGSK Vaccine Effectiveness LRTD\nIncidence of outpatient visits for RSV\nCost per Hospitalization\nMortality, adults hospitalized with RSV\nGSK Vaccine Effectiveness ARI\nED Incidence\nQALYs lost Injection Site ReactionICER ($/QALY)Age ≥65\nLow Assumption High Assumption\nSensitivity analyses, Pfizer Tornado \nDiagram\n29$100 vaccine cost\nOne Year Time HorizonAge-based vaccination recommendation: ≥65 years\n* A\nt low Pfizer vaccine efficacy, the ICER rises to $574,730/QALY574,730$0 $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000\nPfizer Vaccine Effectiveness LRTD\nVaccine Cost\nIncidence of RSV hospitalization\nOutpatient QALYs Lost\nPfizer Vaccine Effectiveness ARI\nIncidence of outpatient visits for RSV\nMortality, adults hospitalized with RSV\nCost per Hospitalization\nED Incidence\nProbability of Serious Adverse EventICER ($/QALY)Age ≥65\nLow Assumption High Assumption\nSensitivity analysis: Vaccine Cost, GSK \n30One Year Time Horizon $- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000 $450,000 $500,000\n $50  $75  $100  $125  $150  $175  $200ICER ($/QALY)\nVaccine Cost\nage ≥60 years age ≥65 years age ≥70 years age ≥75 years \nSensitivity analysis: Vaccine Cost, Pfizer\n31One Year Time Horizon $- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000 $450,000 $500,000\n $50  $75  $100  $125  $150  $175  $200ICER ($/QALY)\nVaccine Cost\nage ≥60 years age ≥65 years age ≥70 years age ≥75 years \nSensitivity analyses, Higher Incidence\n32•Higher incidence in the next 2 slides \nassumes that RT -PCR test sensitivity is \nlower than 95% and that additional RSV testing modalities would detect more cases at every level of care\n1,2\n1For incidence of hospitalization (RSV -NET), in lieu of adjusting observed incidence for RT -PCR sensitivity of 95%, a \n1.4x multiplier is implemented based on Zhang et al. 2016 .\nZhang Y, et al. Serology Enhances Molecular Diagnosis of Respiratory Virus Infections Other than Influenza in Children and Ad ults Hospitalized with \nCommunity -Acquired Pneumonia. J Clin Microbiol . 2016 Dec 28;55(1):79 -89. doi: 10.1128/JCM.01701- 16. PMID: 27795341; PMCID: PMC5228265.\n2For incidence of outpatient and ED visits (McLaughlin et al. 2022), this applies the authors’ multiplier of 1.5x to the \nlower (base case) incidence estimates.\nMcLaughlin JM, et al. Rates of Medically Attended RSV Among US Adults: A Systematic Review and Meta -analysis. Open Forum Infect Dis. 2022 Jun \n17;9(7):ofac300. doi: 10.1093/ ofid/ofac300. PMID: 35873302; PMCID: PMC9301578.\nSensitivity analyses, GSK \nHigher Incidence\n33Age-based vaccination recommendation: ≥65 years\nOne Year Time Horizon $- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000\n $\n50  $75  $100  $125  $150  $175  $200ICER ($/QALY)\nVaccine Cost\nGSK Base age ≥65 years GSK Higher Incidence age ≥65 years\nSensitivity analyses, Pfizer Higher Incidence\n34Age-based vaccination recommendation: ≥65 years\nOne Year Time Horizon $- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000 $450,000\n $50  $75  $100  $125  $150  $175  $200ICER ($/QALY)\nVaccine Cost\nPfizer Base age ≥65 years Pfizer Higher Incidence age ≥65 years\nLimitations\n•Model Structure\n–No risk groups\n–No dynamic transmission. No impact of the vaccine on transmission and \nin\ndirect effects\n–No direct medical costs post-di scharge (e.g. rehab)\n•Uncertain inputs\n–Vaccine cost \n–RSV Incidence\n–Long-t erm efficacy \n35\nSummary\n•Results vary based on:\n–Vaccine Cost\n•ICER: ~80,000 -3 85,000 $/QALY\n–Vaccine Efficacy\n•ICER: ~150,000 -5 75,000 $/QALY\n–Ages Vaccinated\n•ICER: ~100,000 -2 30,000 $/QALY\n–Incidence of Hospitalization\n•ICER: ~30,000 -2 50,000 $/QALY\n36\nThank You\n•Please send comments to:\n•dwhutton@umich.edu\n37", "summary": "Economic Analysis of RSV  Vaccination in Older Adults  David W. Hutton, PhD, MS Associate Professor, Health Management and Policy, School of Public Health Associate Professor of Global Public Health, School of Public Health Associate Professor, Industrial and Operations Engineering, College of Engineering University of Michigan  Research Team University of Michigan •David Hutton, PhD •Lisa Prosser, PhD •Angela Rose, MPH •Kerra Me rcon, MSCDC •Michael Me lgar, MD •Mila Prill , MSPH •Jamison…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/RSV-Adults-02-Hutton-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 37}
{"title": "RSV Adults 03 Ortega Sanchez 508", "content": "Economics of Vaccinating U.S. Adults ≥60 \nyears-old  against \nRespiratory Syncytial Virus\nA SUMMARY REPORT COMPARING MODELS FROM:\nGSK,Pfizer AND University of Michigan -CDC\nIsmael R. Ortega -Sanchez, PhD\nNCIRD/CDC\nACIP Meeting, February 23, 2023\n1Disclaimer : The findings and conclusions in this report are those of the authors and do not necessarily represent the views of \nthe Centers for Disease Control and Prevention. \nNational Center for Immunization & Respiratory Diseases\nConflict of interest\n•GSK model : Daniel Molnar et al.,  [complete list and affiliations, upon request]\n•GSK manufactures the adjuvanted RSVPreF3 vaccine \n•RTI Health Solutions was funded by GSK\n•Pfizer model: Derek Weycker et al., [complete list and affiliations, upon request]\n•Pfizer manufacturers the bivalent RSVpreF vaccine\n•Policy Analysis Inc. was funded by Pfizer\n•UM-CDC model : David W Hutton et al. from Univ Michigan, …, Ismael R Ortega-\nSanchez et al. from CDC [complete author list and affiliations, upon request ]\n•All authors: No conflicts of interest\n2\nEconomic analysis\nPolicy questions: Should adults ≥60 years of age (or ≥65 years of age) receive \none dose of Respiratory Syncytial Virus (RSV) vaccine (GSK or Pfizer product) for \nthe prevention of RSV disease and its complications?\nQuestion: Is vaccinating adults aged ≥65 years (or ≥60 years) against RSV cost-\neffective ?\nComparator\nUnvaccinated \n≥65yr -olds\n(or ≥60yr -olds)Intervention\nVaccinating≥65yr -olds\n(or ≥60yr -olds)\nB\nase-case scenario: What is the incremental cost -effectiveness of vaccinating adults aged \n≥65 years (or ≥60 years) using RSV vaccine relative to “No vaccination”?\n3\nFocus on key features for model comparison\n•Modeling approach\n•Targeted population(s)\n•Perspective (healthcare vs. societal)\n•Intervention strategy and comparator\n•Inputs for RSV disease burden, vaccine efficacy, and costs\n•Incidence of RSV disease, rates of outcomes \n•Direct and Indirect costs of RSV disease\n•Intervention: Vaccine efficacy, duration of protection, safety and program \ncosts\n•Assumptions\n•Strong, influential assumptions\n4\n5Modeling design and assumptions\nGSK Pfizer UM-CDC\nStatic analytical decision-making models ✔ ✔ ✔\nSensitivity analyses (and probabilistic simulation)✔(✔)✔(✔)✔\nHypothe tical popul ation ≥65yrs-old (and ≥60-yrs-old)✔(✔)✔(✔)✔(✔)\nTime Frame: at least 1 yr. after a dose of RSV vaccine✔ ✔ ✔\nAnalytic Horizon: Age-specific Life Expectancy✔ ✔ ✔\nDiscount rate: 3% ✔ ✔ ✔\nYear of econom ic outcomes measured: 2022✔ ✔ ✔\nSocietal perspective (and healthcare perspective)✔(✔)✔(✔)✔(✔)\n6Inputs and main outcomes\nPrevention of:\n•Outpatient visits for RSV\n•RSV hospitalizations\n•RSV-associated deaths\nQALYs saved$/QALY saved\nNumber needed to\nvaccinate (NNV) to avert an: •Outpatient visit for RSV\n•RSV hospitalization\n•RSV-associated death\nGSK Pfizer UM-CDC\n✔ ✔ ✔\n✔ ✔ ✔\n✔ ✔ ✔\n✔ ✔ ✔\n✔ ✔ ✔\n✔ ✔ ✔\n✔ ✔ ✔\n✔ ✔ ✔\nHCRU = health care resource use\nUMich -CDC: Scenario analysis for age group, \n$100 vaccine cost and vaccine candidate\n7$230 \n$181 \n$155 \n$104 $234 \n$189 \n$166 \n$117 \n $- $50 $100 $150 $200 $250\nage ≥60 years age ≥65 years age ≥70 years age ≥75 years Incremental Cost per QALY saved\nThousands\nAge Group VaccinatedGSK Pfizer\nGSK, Pfizer and UM-CDC models comparison: \nSelected outcome ratios for RSV vaccines\n8UM-CDC \nmodel\nVac Price \n$100GSK \nmodel\nVac Price \n$148\n$ / QALY gained\nVaccinating adults ≥65 yrs. 180,720 68,489\nVaccinating adults ≥60 yrs. 229,895 78,971\n$ / hospitalization averted\nVaccinating  adults ≥65 yrs. 101,406 57,114\nVaccinating adults ≥60 yrs. 133,992 69,638GSK vaccine\nUM-CDC \nmodel\nVac Price \n$100Pfizer\nmodel\nVac Price \n$200\n$ / QALY gained\nVaccinating adults ≥65 yrs. 189,407 43,749\nVaccinating adults ≥60 yrs. 233,779 50,197\n$ / hospitalization averted\nVaccinating  adults ≥65 yrs. 122,886 19,845\nVaccinating adults ≥60 yrs. 161,310 23,271Pfizer vaccine\nUM-CDC model : One-way Sensitivity Analyses\nBase case: Age ≥65yrs $180,720/QALY (GSK), $189,407/QALY (Pfizer)\n9One Year Time Horizon\n* \nAt lower bound of Pfizer vaccine efficacy (VE =6.3%), the ICER rises to >$574 Thousand /QALY$0 $100 $200 $300 $400\nVaccine Cost\nIncidence of RSV hospitalization\nOutpatient QALYs Lost\nGSK Vaccine Effectiveness LRTD\nIncidence of outpatient visits for RSV\nCost per Hospitalization\nMortality, adults hospitalized with RSV\nGSK Vaccine Effectiveness ARI\nED Incidence\nQALYs lost Injection Site ReactionGSK: $/QALY saved ( in thousands )\nLow Assumption High Assumption$0 $100 $200 $300 $400\nPfizer Vaccine Effectiveness LRTD\nVaccine Cost\nIncidence of RSV hospitalization\nOutpatient QALYs Lost\nPfizer Vaccine Effectiveness ARI\nIncidence of outpatient visits for RSV\nMortality, adults hospitalized with RSV\nCost per Hospitalization\nED Incidence\nProbability of Serious Adverse EventPfizer:  $/QALY ( in thousands ) \nLow Assumption High Assumption*\nGSK model : One-way Sensitivity Analyses\nBase case: Age ≥60 years; $ 78,971 /QALY saved\nAverage annual incidence of first RSV ARI event\nPercentage of RSV LRTD cases resulting in hospitalization\nEfficacy against RSV LRTD: Waning rates first vaccination with RSVPreF3 vaccine <24 months\nProbability of death given RSV LRTD\nProportion RSV LRTD within first RSV ARI event\nVaccination costs per administered dose with RSVPreF3 vaccine -Purchase cost per dose – Cost\nRSVPreF3 vaccine: Peak % efficacy after first vaccination against RSV LRTD caused by first RSV \ninfection\nBaseline QALYs -General population\nEfficacy against RSV ARI: Waning rates first vaccination with RSVPreF3 vaccine <24 months\nProbability of AE 'Grade 3 ' after first or revaccination with RSVPreF3 vaccine\n10\nPfizer model : One-way Sensitivity Analyses\nBase case: Age≥60 years: $50,104/QALY saved\n11\nBase case\n\nGSK, Pfizer and UM-CDC models comparison: \nSelected inputs \n12•RSV-hospitalization rate\nGSK: Proportion of MA RSV hospitalized cases identified by PCR, differentiated by age ( Belongia, 2018)\nPfizer : Differentiated by age and comorbidity profile (Pfizer data on file)\nCDC: Differentiated by age (four RSV seasons in CDC RSV-NET data)\n•Unitary medical cost of RSV outcomes\n•GSK: Age -& outcome specific cost for symptomatic RSV LRTD & URTI cases (MA and non -MA) (CMS)\n•Pfizer: Age-, outcome- & comorbidity -specific cost for MA RSV\n•CDC: Age -& outcome -specific cost for MA RSV\n•Initial VE & waning over time\nGSK: Phase 3, monthly waning: ARI (5.36%), LRTD (2.63%) until 12mos, then to 0%\nPfizer: Phase 3, flat 7mos, then linear decay to 0% at 24mos\nCDC: GSK’s & Pfizer’s phase 3, flat 6mos, exponential decay until 12mos, then to 0%\nMA = medically attended, ARI = acute respiratory infection \n13UM-CDC GSK Pfizer\nIncidence of RSV outpatient \nillness (per 100,000 persons per year)1,519 \n(base- case for adults ≥65 years)a1,348 \n(for adults ≥65 years)b2,430 \n(base case for adults \n≥65 years)c\nIncidence of RSV hospitalization (per 100,000 persons per year)108 \n(base- case for adults ≥65 years)d256\n(for adults ≥65 years)b,e300\n(base- case for adults \n≥65 years)c\nDirect medical costs per RSV hospitalization$20,330 –$21,339\n(age- dependent)f$13,112 –$26,224\n(age- dependent)g,h$12,048 –$38,380 \n(age- and comorbidity -\ndependent)h,i\na McLaughlin et al. Open Forum Infect Dis (2022): https://doi.org/10.1093/ofid/ofac300 ; unadjusted for under -detection of RT -PCR testing\nb Adapted from Belongia et al. Open Forum Infect Dis (2018): https://doi.org/10.1093/ofid/ofy316\nc McLaughlin et al. Open Forum Infect Dis (2022): https://doi.org/10.1093/ofid/ofac300 ; Ramirez et al. (under review)\nd RSV -NET, CDC unpublished data\ne Adapted from Falsey et al. NEJM (2005): https://doi.org/10.1056/nejmoa043951 ; Herring et al. Vaccine (2022): https://doi.org/10.1016/j.vaccine.2021.12.002\nf Ackerson et al. J Infect Dis (2020): https://doi.org/10.1093/infdis/jiaa183\ng CMS Medicare Inpatient Hospitals (DRG Average Payments from 2019 dataset)\nh Kaiser Family Foundation (How much more than Medicare do private insurers pay? 2020): https://www.kff.org/medicare/issue-brief/how -much -more-than -medicare-do -private -insurers -pay -a-\nreview -of-the-literature/\ni Merative MarketScan Commercial Claims and Encounters (CCAE) and Medicare Supplemental Coordination of Benefits (MDCR) Databases (2016 -2019)GSK, Pfizer and UM-CDC models: Key differences in \nmodel inputs \nGSK model : Sensitivity of Cost per QALY saved to RSV -\nRelated Hospitalization Rates among Adults ≥60 years\n14S8: Branche et al. (2022b; high BoD\nseason [New York City, 2018 -2019]); \nS9: Branche et al. (2022b; low BoD\nseason [Rochester, 2019 -2020]); \nS10: Zheng et al. (2022; low SES); \nS11: Zheng et al. (2022; medium SES); S12: Zheng et al. (2022; high SES); S13: McLaughlin et al. (2022; \nunadjusted); \nS14: McLaughlin et al. (2022; adjusted); \nS15: Widmer et al. (2012); \nS16: Herring et al. (2022; Belongia et al. \n[2018] estimate); S17: Herring et al. (2022; Falsey et al. \n[2005] estimate); S18: DeMartino et al. (2022); \nS19: Fust et al. (2022a and 2022b).\nNote: BoD = burden of disease; SES = socioeconomic status.\n* Derived from GSK modeling results.\n\nS3:\nS6:\nS1:\nS7:S5:\nS4:\nS2:\nBase- casePfizer model : Sensitivity of Cost per QALY saved to RSV -\nRelated Hospitalization Rates among Adults ≥60 years\n15• S1: Pooled unadjusted rates from \nMcLaughlin et al. (active prospective \nsurveillance studies only)1\n• S2: Based on pooled adjusted rates from \nMcLaughlin et al. 1.5 -fold (active \nprospective surveillance studies only)1\n• S3: Rates in Rochester, NY , averaged \nacross all study years, from Branche et al.2\n• S4: Rates in New York, NY , averaged \nacross all study years, from Branche et al.2\n• S5: Rates averaged across all study years \nand accounting for the proportion of RSV-\nconfirmed cases treated in hospital from \nBelongia et al.3\n• S6: Rates based on Matias et al.4\n• S7: Rates based on Widmer et al.5\nBase Case : Ongoing unvetted prospective \nstudy with adjusted RSV detection rates of 1.6-to 1.7-fold. Pfizer Inc. data on file 1. McLaughlin JM, et al. Open Forum Infectious Diseases . 9(7), 2022\n2. Branche AR et al. Clinical Infectious Diseases. 2021;74(6):1004- 1011. \n3. Belongia et al. Open Forum Infect Dis . 2018;5(12):ofy316.\n4. Matias et al. BMC Public Health. 2017;17(1):271.\n5. Widmer et al. Influenza and Other Respiratory Viruses . 2014;8(3):347-352.\nUM-CDC model : Sensitivity of Cost per QALY saved to RSV -\nRelated Hospitalization Rates among Adults ≥65 years\n16Base case: mean value of the burden adjusted rate over RSV seasons: 2015 -16, 2016- 17, 2017- 18, and 2018- 19. Adjusted rate for 95% sensiti vity of PCR testing. CDC RSVnet\nLower bound: mean of  lower confidence limit estimates across all 4 seasons assuming 95% sensitivity of PCR testing. \nUpper bound: mean of upper confidence limit estimates across all 4 seasons assuming 71% sensitivity of PCR testing.$180,720 $189,407 \n $- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000\n0 50 100 150 200 250 300 350Incremental Cost per QALY saved\nIncidence of RSV Hospitalization per 100,000 persons per yearGSK\nPfizer\nIncidence Range\nMinimum\nBase Case\nHigher Incidence\nScenario\nGSK, Pfizer and UM-CDC:  Initial or Early Peak \nof Vaccine Efficacy\n17a VE over mean 6 –7 months of follow up in phase 3 clinical trials\nb Manufacturer phase 3 trial data; VE against medically attended acute respiratory illness\nc GSK phase 3 trial data; IDWeek abstract ; VE against acute respiratory illness, regardless of whether medically attended\nd Manufacturer phase 3 trial data; GSK: VE against medically attended lower respiratory tract disease; Pfizer: VE against medica lly attended lower respiratory tract illness with ≥3 lower \nrespiratory symptomse Manufacturer phase 3 trial data; GSK: IDWeek abstract \nVE against lower respiratory tract disease, regardless of whether medically attended; Pfizer: IDWeek abstract VE against lower \nrespiratory tract illness with ≥3 lower respiratory symptoms, regardless of whether medically attended (95% CI applied)UM-CDC GSK Pfizer\nGSK vaccine Pfizer vaccine\nVaccine efficacy (VE) against RSV \noutpatient illnessa79.0 \n(54.3– 91.5)b69.2 \n(30.0– 88.0)b71.7 \n(56.7– 82.3)c69.2 \n(30.0– 88.0)b\nVE against RSV hospitalization and emergency department visit\na87.5 \n(58.4– 96.2)d80.0 \n(6.3– 97.9)d82.6 \n(57.9– 94.1)e85.7\n(37.9– 98.4)e\nGSK, Pfizer and UM-CDC: Assumption on \nwaning of vaccine efficacy (VE) per outcome \n18GSKVE peaks at 2 months then wanes per month         \nRSV-ARI = 5.36% points per month (range: 0.00 -\n13.37%)      RSV-LRTD = 2.63% points per month (range: 0.00 -\n10.95%)No residual protection after 12 monthsPfizerInitial VE assumed to persist for 7 months, Then to decline linearly to 0% effectiveness at 24 monthsResidual though declining protection up to 24 \nmonthsUM-CDCVaccine and outcome -specific\nFor both vaccines:\nExponential decay up to 12 months and then 0% afterwards; calibrated such that the \nfirst 6 months VE equals the trial estimate\n\nPfizer : Impact of vaccine’s duration of protection \n(DoP) assumption on ≥65yrs Cost per QALY saved\n19\nBase- Case\nBase- Case*\n* RSV hospitalization incidence labelled “CDC x1.4” used data presented by CDC at IDWeek 2022 (Havers et al. https://doi.org/10.1093/ofid/ofac492.1828 ), \nupwardly adjusted by a factor of 1.4 (based on Zhang et al. https://doi.org/10.1128/jcm.01701 -16).\nComparison of GSK and Pfizer vaccines: base case & \nscenario $/QALY results using UM-CDC model \n20aRecommendation = vaccination at age ≥65 years; vaccine unit cost = $100; incidence rates of RSV outcomes unadjusted for incre ased diagnostic yield from testing \nin addition to RT -PCR on a respiratory specimen; vaccine efficacy only considered for one year post -vaccination\nb Base case incidence rates adjusted upward for increased diagnostic yield from testing in addition to RT -PCR on a respiratory s pecimen (1.5x for outpatient illness \n[McLaughlin et al; Open Forum Infect Dis (2022)], 1.4x for inpatient illness [Zhang et al; J Clin Microbiol (2016)])Scenario GSK Pfizer\nVaccine cost $200 per dose (one year time frame) $374,530 $384,267\nVaccinating adults aged ≥60 years $229,895 $233,779\nMedical cost for hospitalization (lower bound) $199,018 $205,236\nBase case a (Vaccine Price $100, 1 year time frame) $180,720 $189,407\nHigher incidence of RSV b $91,028 $104,160\nVaccine cost $50 per dose (one year time frame) $85,815 $91,977\nLimitations\n21•Factors not considered that may result in overestimating the ICER \n(underestimating the cost -effectiveness) of RSV vaccination\n•None of the 3 models included RSV- related medical costs incurred after \ndischarge from an RSV- associated hospitalization or emergency department \nvisit: \n•Stay in long-term care or rehabilitation facility\n•Assisted living at home\n•Productivity losses incurred by caregivers whose support is needed post-discharge\n•All of the 3 models assumed no indirect effects of vaccination (i.e., no protection against RSV transmission)\n•Vaccine efficacy beyond clinical trial follow -up time (6 –7 months) is unknown\n•All 3 models assumed non- zero declining efficacy beyond 6– 7 months \n(UM-CDC : 12 months, GSK: 12 months, Pfizer : 24 months ).\nConclusion\n22•Differences in key inputs among GSK, Pfizer and UM-CDC models explain differences in results:\n•Incidence of hospitalization  \n•Duration of vaccine efficacy\n•Medical costs\n•Vaccine costs\n•Assumptions and selection of input data were crucial in differences in ICERs\n•Adjustment approach of incidence rates of Hospitalization, ER and Outpatient\n•Selection of medical costs sources and data extraction approach\n•Base-case in the 3 models:\n•Vaccination would significantly reduce RSV disease burden in older adults \n•VE clinical trials data and assumptions support impact on disease reduction\n•Economic value of RSV vaccines appear to be costly and could be cost-effective \n•RSV incidence, related healthcare costs, initial VE and duration combined with reasonable \nvaccine price would determine the cost-effectiveness value of RSV vaccination\nAcknowledgements \nFrom NCIRD/CDC\n•Michael Melgar\n•Jamison Pike\n•Fiona Havers\n•Meredith McMorrow\nA\nlso:\n•Adult RSV working group members\n•Econ Team members at ISD/NCIRD\n23\n\nEnd of Summary", "summary": "Economics of Vaccinating U.S. Adults ≥60  years-old  against  Respiratory Syncytial Virus A SUMMARY REPORT COMPARING MODELS FROM: GSK,Pfizer AND University of Michigan -CDC Ismael R. Ortega -Sanchez, PhD NCIRD/CDC ACIP Meeting, February 23, 2023 1Disclaimer : The findings and conclusions in this report are those of the authors and do not necessarily represent the views of  the Centers for Disease Control and Prevention.  National Center for Immunization & Respiratory Diseases Conflict of…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/RSV-Adults-03-Ortega-Sanchez-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 24}
{"title": "RSV Adults 04 Melgar 508", "content": "Centers for Disease Control and Prevention \nEvidence to  Recommendations Framework \nRespiratory  Syncytial Virus (RSV) in  Adults \nGSK adjuvanted RSVpreF3 vaccine in older adults \nPfizer bivalent RSVpreF vaccine in older adults \nMichael Melgar, MD \nLead, Adult RSV ACIP Work Group ACIP Meeting February 23, 2023 \n \n   \n \n   \n \n   \n \n   \n Evidence to Recommendations (EtR ) Framework\nPoli\ncy Questions \nShould vaccination with GSK RSVpreF3 vaccine (120µg antigen + AS01E adjuvant, 1 \ndose IM), rather than no vaccine, be recommended in persons aged ≥65 years? \nShould v\naccination with GSK RSVpreF3 vaccine (120µg antigen + AS01E adjuvant, 1 \ndose IM), rather than no vaccine, be recommended in persons aged ≥60 years? \nShould v\naccination with Pfizer bivalent RSVpreF vaccine (120µg antigen, 1 dose IM), \nrather than no vaccine, be recommended in persons aged ≥65 years? \nShould vaccination with Pfizer bivalent RS VpreF vaccine (120µg antigen, 1 dose IM), \nrather than no vaccine, be recommended in persons aged ≥60 years? \n2 \n \n    \n      \n      \n     \n      \n  \n       \n      \n          \n       Evidence to Recommendations (EtR ) Framework \nEtR Domain Question(s) \nPublic Health Problem Is the problem of public health importance? \nBenefits and Harms How substantial are the desirable anticipated effects? \nHow substantial are the undesirable anticipated effects? \nDo the desirable effects outweigh the undesirable effects? \nValues Does the target population feel the desirable effects are large relative \nto the undesirable effects? \nIs there important variability in how patients value the outcome? \nAcceptability Is the intervention acceptable to key stakeholders? \nFeasibility Is the intervention feasible to implement? \nResource Use Is the intervention a reasonable and efficient allocation of resources? \nEquity What would be in the impact of the intervention on health equity? \n3 \n \n   Evidence to Recommendations (EtR ) Framework \nEtR Domain \nPublic Health  Prob lem \nBenefits  and Harms \nValues Acceptability Feasibility Resource Use Equity Data on RSV in older adults will be presented \n4 \n \n  Evidence to Recommendations (EtR ) Framework \nEtR Domain \nPublic Health  Problem  \nBenefits  and Harms \nValues \nAcceptability \nFeasibility \nResource Use \nEquity Use of RSV vaccines broadly will be presented \n5 \n \n   Evidence to Recommendations (EtR ) Framework \nEtR Domain \nPublic Health  Problem \nBenefits  and Harms \nValues \nAcceptability \nFeasibility \nResource Use \nEquity Manufacturer- specific data will be presented \n6 \n \n   Public Health Problem \nIs RSV among older adults of public health importance? \n \n    \n    \n  \n     \n   \n     \n Among adults ≥65   years of  \nage in the United States, \nRSV  is associated with*… \n*There  is substantial uncertainty  \nin burden  of disease,  reflected  in  \nwide ranges here.  \n6,000– 10,0001–3 \ndeaths/year \n60,000 –160,0004–8 \nhospitalizations/year \n0.9–1.4 million5 \nmedical encounters/year \n5. McLaughlin et al, Open Forum Infect Dis (2022): https://doi.org/10.1093/ofid/ofac300 \n6. Zheng et al, Pneumonia (2022): https://doi.org/10.1186/s41479- 022-00098 -x \n7. Branche et al, Clinical Infect Dis (2022): https://doi.org/10.1093/cid/ciab595 \n8. CDC RSV -NET data 2016– 2020 (unpublished) 1. Thompson et al, JAMA (2003): https://doi.org/10.1001/jama.289.2.179 \n2. Matias et al, Influenza Other Respi Viruses (2014): https://doi.org/10.1111/irv.12258 \n3. Hansen et al, JAMA Network Open (2022): \nhttps://doi.org/10.1001/jamanetworkopen.2022.0527 \n4. Widmer et al, JAMA Network Open (2012): https://doi.org/10.1093/infdis/jis309 8 \n    \n  \n    \n0 50 100 150 200 250 300 350 Hospitalizations per 100,000 237 to 325 \n42 to 53 \n7 to 11 26 to 36 50 to 67 69 to 84 111 to 133 \n18-49 yr 50-59 yr 60-64 yr 65-69 yr 70-79 yr 80+ yr Overall \n2016-17 2017-18 2018-19 2019-20  \n   \n             RSV-associated hospitalization rates by adult age group,\nRSV-NET 2016–2020 \nRSV-NET: unpublished data; https://www.cdc.gov/rsv/research/rsv-net/overview-methods.html. \nRates are adjusted for the frequency of RSV testing during recent prior seasons and the sensitivity of RSV diagnostic tests.. Slide credit: Fiona Havers 9 \n\n \n 25 23 \n20 20 18 \n15 \n5 10 \n5 31 \n0 \n18-49 50-64 ≥65 \nAge group (years) \nICU admission Death \nSlide credit: Fiona Havers Percent  \n   \n \n Outcomes among adults ≥18 years hospitalized for \nRSV: RSV -NET 2017–18 to 2019–20 seasons (n=8,214) \nSevere outcomes \nfrequent among adults of all ages hospitalized for RSV \n10 \n  \n  \n \n \n  \n   \n     \n    \n     Adults with certain underlying medical conditions are \nat higher risk of RSV hospitalization \nImmune compromise, especially hematopoietic stem cell transplant and \nsolid organ transplant \nCardiovascular disease (e.g., congestive heart failure) \nDiabetes mellitus \nChronic obstructive pulmonary disease (COPD) \nAsthma \n1. Anderson et al, Diagn Microbiol Infect Dis (2016): https://doi.org/10.1016/j.diagmicrobio.2016.02.025 \n2. Prasad et al, Clin Infect Dis (2020): https://doi.org/10.1093/cid/ciaa730 \n3. Kujawski et al, Plos One (2022): https://doi.org/10.1371/journal.pone.0264890 \n4. Branche et al, Clin Infect Dis (2022): https://doi.org/10.1093/cid/ciab595 11 \n   \n    \n    \n  \n  Summary \nRSV is a frequent, often unrecognized, cause of severe respiratory \nillness, with incidence increasing with age among older adults \nHigh proportion of those hospitalized with RSV have severe outcomes, including ICU admission and death \nDeath is more common with increasing age \n12 \n   Public Health Problem- Work Group Interpretation \nIs RSV   disease   of public   health   importance   among   adults   aged   ≥65  \nyears? \nNo Prob\nably \nNo Pro\nbably \nYes Ye\ns Va\nries Don\n’t \nknow \n13 \n Benefits and Harms \n-How substantial are the desirable anticipated effects? \n-How substantial are the undesirable anticipated effects? \n-Do the desirable effects outweigh the undesirable effects?  \n  \n   Benefits and Harms \nGSK adjuvanted RSVpreF3 vaccine \n– Grading of Recommendations, Assessment, Development and \nEvaluation ( GRADE) Summary \n– Number-needed-to -vaccinate (NNV) analysis \nPfizer bivalent RSVpreF vaccine \n– GRADE Summary \n– NNV analysis \n15 \n16  \n  \n   \n   \n  \n   \n  \n \n  GRADE Framework: PICO Question \nPopulation \nIntervention \nComparison \nOutcomes Persons aged ≥60 years \nGSK RSVpreF3 vaccine (120 μg antigen + AS01E adjuvant, 1 dose IM) \n-or-\nPfi\nzer bivalent RSVpreF vaccine (120µg antigen, 1 dose IM) \nNo RSV vaccine \nRS\nV lower respiratory tract illness/disease (LRTI/LRTD) \nMedically attended RSV LRTI/LRTD \nHospitalization for RSV respiratory illness \nSevere RSV respiratory illness requiring supplemental O2 or other \nrespiratory support \nDeath due to RSV respiratory illness \nSerious Adverse Events (SAEs) \nInflammatory neuropathy (e.g., Guillain -Barré syndrome) \nReactogenicity (grade ≥3) \nGRADE: GSK adjuvanted RSVpreF3 \n17 \n   \n       \n     \n     \n   \n    \n      \n              \n               \n           \n    \n         \n  \n              \n     \n     GSK, Benefits: vaccine efficacy estimates \nOutcome​ Importance Data sources Vaccine efficacy estimatea \n(95% confidence interval) Concerns in certainty \nassessment \nBenefits \nRSV Lower Respiratory Tract Disease (LTRD) Critical \nOne phase 3 RCTb 82.5% (60.9%, 92.1%) Indirectness (serious)c \nMedically attended RSV LRTD Critical One phase 3 RCTb 87.5% (58.4%, 96.2%) Indirectness (serious)c \nHospitalization for RSV respiratory illness Important \nOne phase 3 RCTb Unable to evaluated \nSevere RSV respiratory illness requiring O2/respiratory support Important \nOne phase 3 RCTb Unable to evaluatee \nDeath due to RSV respiratory illness Important One phase 3 RCTb Unable to evaluatef \nRCT: Randomized control trial \na Efficacy estimates were independently calculated using counts of events and participants in the GSK pivotal phase 3 trial int erim analysis. Data provided by manufacturer. \nEfficacy was calculated as 1 – relative risk. Events of each outcome were included if they occurred on or after day 15 after injection. \nb Papi A, Ison MG, Langley JM, et al. Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older Adults. 2023. NEJM. https://doi.org/10.1056/nejmoa2209604 \nc Underrepresentation of adults aged ≥80 years, exclusion of persons with immune compromise. \nd Three RSV -associated hospitalizations occurred in the modified exposed set up to the data lock point for the interim analysis. Information was not provided by study arm \n(intervention vs. placebo) to avoid unblinding of cases. \ne 31 cases of LRTD requiring oxygen supplementation were identified; 4 of the 31 cases were associated with RSV. All 4 cases oc curred in the placebo arm. Measures of \nrelative and absolute risk were not calculated due to small number of events. \nf No RSV -associated deaths were recorded in the interim analysis. 18 \n \n   \n  \n   \n \n   \n \n   \n          \n       \n  \n        \n       GSK, Harms: relative risk \nOutcome​ Importance Data sources Relative risk estimatea \n(95% confidence interval) Concerns in certainty \nassessment \nHarms \nSerious adverse events (SAEs) Critical One phase 3 RCT, \none phase 1/2 RCT 1.03 (0.92, 1.17) None serious \nInflammatory neuropathy Important One phase 3 RCT one phase 1/2 RCT Unable to evaluateb \nReactogenicity (grade ≥3) Important One phase 3 RCT one phase 1/2 RCT 4.10 (1.99, 8.45) None serious \nRCT: Randomized control trial \na Pooled relative risk estimates were independently calculated using counts of events and participants in the GSK pivotal phase 3 trial interim analysis ( Papi A, et al. NEJM \n2023 https://doi.org/10.1056/nejmoa2209604), as well as from a placebo -controlled phase 1/2 dosing selection study (Leroux -Roels I, et al. J Infect Dis. 2022 \nhttps://doi.org/10.1093/infdis/jiac327). Data provided by manufacturer. \nb No events recorded in studies included in GRADE. One event of Guillain- Barré syndrome recorded in a recipient of the investigational vaccine in an open label trial without a \nplacebo arm. This study was not included in GRADE assessment due to lack of an unvaccinated comparator. \n19 \n \n   \n  \n   \n \n   \n \n   \n        \n          \n       \n  \n        \n     GSK, Harms: relative risk \nOutcome​ Importance Data sources Relative risk estimatea \n(95% confidence interval) Concerns in certainty \nassessment \nHarms \nSerious adverse events (SAEs) Critical One phase 3 RCT, \none phase 1/2 RCT 1.03 (0.92, 1.17) None serious \nInflammatory neuropathy Important One phase 3 RCT one phase 1/2 RCT Unable to evaluateb \nReactogenicity (grade ≥3) Important One phase 3 RCT one phase 1/2 RCT 4.10 (1.99, 8.45) None serious \nRCT: Randomized control trial \na Pooled relative risk estimates were independently calculated using counts of events and participants in the GSK pivotal phase 3 trial interim analysis ( Papi A, et al. NEJM \n2023 https://doi.org/10.1056/nejmoa2209604), as well as from a placebo -controlled phase 1/2 dosing selection study (Leroux -Roels I, et al. J Infect Dis. 2022 \nhttps://doi.org/10.1093/infdis/jiac327). Data provided by manufacturer. \nb No events recorded in studies included in GRADE. One event of Guillain- Barré syndrome recorded in a recipient of the investigational vaccine in an open label trial without a \nplacebo arm. This study was not included in GRADE assessment due to lack of an unvaccinated comparator. \nTotal of 1 case of inflammatory neuropathy among approximately \n15,000 investigational vaccine recipients across all clinical trials 20 \n \n  \n   \n    \n  \n      \n   \n   \n    \n​    Summary of GRADE for GSK RSVPreF3 vaccine in older adults \nOutcome​ Importance Design \n(# of studies)​Findings​ Evidence type​\nBenefits \nRSV Lower Respiratory Tract \nDisease (LTRD) Critical RCT (1) GSK RSVpreF3 likely reduces RSV LRTD. Moderate \nMedically attended RSV LRTD Critical RCT (1) GSK RSVpreF3 likely reduces medically attended RSV LRTD. Moderate \nHospitalization for RSV respiratory illness Important RCT (1) Only three events, unknown whether in vaccine or placebo arm Unable to \nevaluate \nSevere RSV respiratory illness requiring O2/respiratory support Important RCT (1) Measures of relative and absolute risk not calculated due to small number of events. Unable to \nevaluate \nDeath due to RSV respiratory illness Important RCT (1) No events observed Unable to \nevaluate \nHarms \nSerious adverse events​ Critical RCT (2) GSK RSVpreF3 results in little to no differences in SAEs. High \nInflammatory neuropathy Important RCT (2) No events observed in placebo -controlled trials. Single case \nobserved in an open- label uncontrolled study. Unable to \nevaluate \nReactogenicity (grade ≥3) Important RCT (2) GSK RSVpreF3 increases severe reactogenicity events. High \n21 \n   \n Summary of GRADE for GSK RSV vaccine in older adults \nOverall evidence rating: Moderate certainty 22 \n  \n  \n  \n  \n   \n \n \n              \n             \n          \n        \n             \n       Number needed to vaccinate (NNV): GSK RSVpreF3 \nDerived from cost effectiveness analysis performed by U. Michigan \nTime horizon: one year \nNumber of vaccinations \nrequired to prevent… Adults aged ≥65 years Adults aged ≥60 years \n1 RSV outpatient visita 84 vaccinations 90 vaccinations \n1 RSV hospitalizationb 1,097 vaccinations 1,348 vaccinations \n1 RSV deathc 21,442 vaccinations 27,284 vaccinations \na Incidence rates of RSV illness requiring outpatient visit taken from McLaughlin et al, OFID (2022) (unadjusted for RSV under -detection by NP swab RT-PCR). Vaccine efficacy (VE) against \nthis outcome assumed to be equal to that against medically attended acute respiratory illness (ARI) caused by RSV (GSK AReSVi-006 trial, unpublished). \nb Incidence rates of RSV hospitalization taken from RSV -NET 2015–2019 (unpublished). VE against RSV -associated hospitalization assumed to be equal to that against medically attended \nlower respiratory tract disease (LRTD) caused by RSV (GSK AReSVi-006 trial, unpublished). \nc Probability of in-hospital death among adults hospitalized for RSV taken from RSV -NET 2015–2019 (unpublished). VE against RSV -associated death assumed to be equal to that against \nmedically attended lower respiratory tract disease (LRTD) caused by RSV (GSK AReSVi-006 trial, unpublished). 23 \n   \n       \n \n   \n  \n    \n  Benefits and Harms GSK adjuvanted RSVpreF3 vaccine \nHow substantial are the desirable anticipated effects among adults \nag\ned ≥65 years (relative to no RSV vaccine)? \n– How substantial is the anticipated protective effect against: \n• R\nSV lower respiratory tract disease (LRTD) \n• Medically attended RSV LRTD \n• Hospitalization for RSV respiratory illness \n• Severe RSV respiratory illness requiring supplemental O2/respiratory \nsupport \n• Death due to RSV respiratory illness \nMinimal Small Moderate Large Varies Don’ t know \n24 \n   \n       \n \n \n  Benefits and Harms GSK adjuvanted RSVpreF3 vaccine \nHow substantial are the undesirable anticipated effects among \nad\nults aged ≥65 years (relative to no RSV vaccine)? \n– How substantial is the anticipated effect on: \n• S\nerious Adverse Events (SAEs) \n• Inflammatory neuropathy (e.g., Guillain- Barré Syndrome) \n• Reactogenicity (grade ≥3) \nMinimal Small Mode rate Large Varies Don’t know \nMinority opinion 25 \n     \n   \n   \n  Benefits and Harms GSK adjuvanted RSVpreF3 vaccine \nDo the desirable effects outweigh the undesirable effects among \nadu\nlts aged ≥65 years? \n– What \nis the balance between the desirable effects relative to \nthe u\nndesirable effects? \nFavors  intervention  (GSK RSVpreF3  vaccine) \nFavors  comparison (no  vaccine) \nFavors both \nFavors neither \nUnclear \nMinority opinion 26 \n GRADE: Pfizer bivalent RSVpreF \n27 \n \n   \n     \n    \n   \n   \n  \n     \n          \n              \n                  \n          \n    \n  \n     Pfizer, Benefits: vaccine efficacy estimates \nOutcome​ Importance Data sources Vaccine efficacy estimatea \n(95% confidence interval) Concerns in certainty \nassessment \nBenefits \nRSV Lower Respiratory Tract Illness (LRTI)\nb Critical One phase 3 RCT 85.7% (37.9%, 98.4%) Indirectness (serious)c \nMedically attended RSV LRTIb Critical One phase 3 RCT 80.0% (6.3%, 97.9%) Indirectness (serious)c \nHospitalization for RSV respiratory illness Important Counts not \nprovided Unable to evaluated \nSevere RSV respiratory illness \nrequiring O2/respiratory support Important Counts not \nprovided Unable to evaluated \nDeath due to RSV respiratory illness Important One phase 3 RCT Unable to evaluatee \nRCT: Randomized control trial \na Efficacy estimates were independently calculated using counts of events and person- time observation in the Pfizer pivotal phase 3 trial interim analysis. Data provided by \nmanufacturer. Efficacy was calculated as 1 – incidence rate ratio. Events of each outcome were included if they occurred on or a fter day 15 after injection. \nb Pfizer pivotal phase 3 trial included co -primary outcomes of LRTI with ≥2 lower respiratory signs or symptoms, and LRTI with ≥3 lower respiratory signs or symptoms. In \nGRADE, the outcome of LRTI with ≥3 lower respiratory signs or symptoms was used. \nc Underrepresentation of adults aged ≥80 years, exclusion of persons with immune compromise. \nd Counts of event were not provided by manufacturer. \ne No RSV -associated deaths were recorded in the interim analysis. 28 \n \n   \n   \n   \n \n   \n \n   \n           \n      \n           \n     \n         Pfizer, Harms: relative risk \nOutcome​ Importance Data sources Relative risk estimatea \n(95% confidence interval) Concerns in certainty \nassessment \nHarms \nSerious adverse events (SAEs) Critical One phase 3 RCT \none phase 1/2 RCT 1.01 (0.88 to 1.16) None serious \nInflammatory neuropathy Important One phase 3 RCT one phase 1/2 RCT Unable to evaluateb \nReactogenicity (grade ≥3) Important One phase 3 RCT one phase 1/2 RCT 1.47 (0.88 to 2.46) Imprecision (serious)c \nRCT: Randomized control trial \na Pooled relative risk estimates were independently calculated using counts of events and participants in the Pfizer pivotal phas e 3 trial interim analysis, as well as from a \nplacebo- controlled phase 1/2 formulation selection study ( Falsey A, et al. J Infect Dis. 2022 https://doi.org/10.1093/infdis/jiab611p ). Data provided by manufacturer. \nb In the Pfizer pivotal phase 3 trial interim analysis, 2 events of Guillain -Barré syndrome were recorded in the intervention arm , compared with zero in the placebo arm. No \nevents were recorded in the phase 1/2 formulation selection study. Measures of relative and absolute risk were not calculated due to small number of events. \nc 95% confidence interval for measure of absolute risk included potential for both benefit and harm. \n29 \n \n   \n   \n   \n \n   \n \n   \n                \n      \n           \n     \n         Pfizer, Harms: relative risk \nOutcome​ Importance Data sources Relative risk estimatea \n(95% confidence interval) Concerns in certainty \nassessment \nHarms \nSerious adverse events (SAEs) Critical One phase 3 RCT \none phase 1/2 RCT 1.01 (0.88 to 1.16) None serious \nInflammatory neuropathy Important One phase 3 RCT one phase 1/2 RCT Unable to evaluateb \nReactogenicity (grade ≥3) Important One phase 3 RCT one phase 1/2 RCT 1.47 (0.88 to 2.46) Imprecision (serious)c \nRCT: Randomized control trial \na Pooled relative risk estimates were independently calculated using counts of events and participants in the Pfizer pivotal phas e 3 trial interim analysis, as well as from a \nplacebo- controlled phase 1/2 formulation selection study ( Falsey A, et al. J Infect Dis. 2022 https://doi.org/10.1093/infdis/jiab611p ). Data provided by manufacturer. \nb In the Pfizer pivotal phase 3 trial interim analysis, 2 events of Guillain -Barré syndrome were recorded in the intervention arm , compared with zero in the placebo arm. No \nevents were recorded in the phase 1/2 formulation selection study. Measures of relative and absolute risk were not calculated due to small number of events. \nc 95% confidence interval for measure of absolute risk included potential for both benefit and harm. \nTotal of 2 cases of inflammatory neuropathy among approximately \n26,000 investigational vaccine recipients across all clinical trials 30 \n   \n \n  \n \n  \n   \n   \n      \n       \n​    Summary of GRADE for Pfizer RSV vaccine in older adults \nOutcome​ Importance Design \n(# of studies)​Findings​ Evidence type​\nBenefits \nRSV Lower Respiratory Tract \nIllness (LRTI) Critical RCT (1) Pfizer RSVpreF likely reduces RSV LRTI. Moderate \nMedically attended RSV LRTI Critical RCT (1) Pfizer RSVpreF likely reduces medically attended RSV LRTI. Moderate \nHospitalization for RSV respiratory illness Important No data Unable to \nevaluate \nSevere RSV respiratory illness requiring O2/respiratory support Important No data Unable to \nevaluate \nDeath due to RSV respiratory illness Important RCT (1) No events observed Unable to \nevaluate \nHarms \nSerious adverse events​ (SAEs) Critical RCT (2) Pfizer RSVpreF results in little to no difference in SAEs. High \nInflammatory neuropathy Important RCT (2) Measures of relative and absolute risk not calculated due to \nsmall number of events. Unable to \nevaluate \nReactogenicity (grade ≥3) Important RCT (2) Pfizer RSVpreF likely increases severe reactogenicity events. Moderate \n31 \n \n Summary of GRADE for Pfizer RSV vaccine in older adults \nOverall evidence rating: Moderate certainty 32 \n  \n  \n  \n  \n   \n   \n \n              \n           \n          \n              \n            \n                Number needed to vaccinate (NNV): Pfizer RSVpreF \nDerived from cost effectiveness analysis performed by U. Michigan \nTime horizon: one year \nNumber of vaccinations \nrequired to prevent… Adults aged ≥65 years Adults aged ≥60 years \n1 RSV outpatient visita 95 vaccinations 103 vaccinations \n1 RSV hospitalizationb 1,275 vaccinations 1,567 vaccinations \n1 RSV deathc 24,927 vaccinations 31,717 vaccinations \na Incidence rates of RSV illness requiring outpatient visit taken from McLaughlin et al, OFID (2022) (unadjusted for RSV under -detection by NP swab RT-PCR). Vaccine efficacy (VE) against \nthis outcome assumed to be equal to that against medically attended acute respiratory illness (ARI) caused by RSV (Pfizer REN OIR trial, unpublished). \nb Incidence rates of RSV hospitalization taken from RSV -NET 2015–2019 (unpublished). VE against RSV -associated hospitalization assumed to be equal to that against medically attended \nlower respiratory tract illness (LRTI) with ≥3 symptoms, caused by RSV (Pfizer RENOIR trial, unpublished). \nc Probability of in-hospital death among adults hospitalized for RSV taken from RSV -NET 2015–2019 (unpublished). VE against RSV -associated death assumed to be equal to that against \nmedically attended lower respiratory tract illness (LRTI) with ≥3 symptoms, caused by RSV (Pfizer RENOIR trial, unpublished). 33 \n   \n       \n \n   \n  \n    \n  Benefits and Harms Pfizer bivalent RSVpreF vaccine \nHow substantial are the desirable anticipated effects among adults \nag\ned ≥65 years (relative to no RSV vaccine)? \n– How substantial is the anticipated protective effect against: \n• R\nSV lower respiratory tract disease (LRTD) \n• Medically attended RSV LRTD \n• Hospitalization for RSV respiratory illness \n• Severe RSV respiratory illness requiring supplemental O2/respiratory \nsupport \n• Death due to RSV respiratory illness \nMinimal Small Moderate Large Varies Don’t know \n34 \n   \n       \n \n \n  Benefits and Harms Pfizer bivalent RSVpreF vaccine \nHow substantial are the undesirable anticipated effects among \nad\nults aged ≥65 years (relative to no RSV vaccine)? \n– How substantial is the anticipated effect on: \n• S\nerious Adverse Events (SAEs) \n• Inflammatory neuropathy (e.g., Guillain- Barré Syndrome) \n• Reactogenicity (grade ≥3) \nMinimal Small Mod erate Large Varies  Don’t know \nMinority opinion 35 \n       \n   \n   \n  Benefits and Harms Pfizer bivalent RSVpreF vaccine \nDo the desirable effects outweigh the undesirable effects among \nadu\nlts aged ≥65 years? \n– What \nis the balance between the desirable effects relative to \nthe u\nndesirable effects? \nFavors  intervention  (Pfizer  RSVpreF  vaccine) \nFavors comparison (no vaccine) \nFavors both \nFavors neither \nUnclear \nMinority opinion 36 \n  \n Values \nDo older adults feel the desirable effects of RSV vaccination are \nlarge relative to the undesirable effects? \nIs there important variability in how older adults value the main \noutcomes? \n  \n \n    \n  \n    \n \n  \n    Survey of vaccination intent for an RSV vaccine among \nU.S. adults aged ≥60 years \nDesigned to assess vaccination intentions for a hypothetical RSV vaccine \nData collection period: December 23– 31, 2022 \nFinal sample: 586 respondents (98.7% completion rate) \nGENDER RACE/ETHNICITY AGE \n56.3% Female \n43.7% Male or other \ngender identity 74.9% N on-Hispanic White \n12.4% Non- Hispanic Black \n9.1% Hispanic 70.6% 60 –70 years \n29.4% ≥70 years \nCDC and University of Iowa/RAND survey, unpublished 38 \n \n \nDefinitely or \nprobably would get vaccinated \nUnsure \nDefinitely or probably would not \nget vaccinated \n39    \n     \n  68% of respondents said they ‘definitely’ or ‘probably’ \nwould get vaccinated if a safe and effective FDA-\napproved RSV vaccine was available \nCDC and University of Iowa/RAND survey, unpublished \n \n \nDefinitely or \nprobably would get vaccinated \nUnsure \nDefinitely or probably would not \nget vaccinated \n40     \n  77% said they ‘definitely’ or ‘probably’ would get an \nRSV vaccine if it were recommended by a healthcare \nprovider \nCDC and University of Iowa/RAND survey, unpublished \n \n \n \n \n    % of respondents who expressed hesitancy to receive an RSV vaccine (n=378) \n0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% \nI don’t know enough about RSV \nLong-term safety \nShort-term safety \nCost concerns \nDon’t trust an RSV vaccine \nI’ve gotten too many vaccines \nRSV vaccine might cause RSV \nRSV vaccine might make infection worse \nNone of these \nAn RSV vaccine wouldn’t work well \nOther \nI don’t like needles \nNot at risk of getting RSV \nWould not get sick if I got RSV \nAgainst my religious beliefs \nI’ve already had RSV \nNo time to get vaccinated \nRSV is not real 41.0% \n39.4% \n29.1% \n13.0% \n11.9% \n11.1% \n9.3% \n9.3% 9.3% \n5.8% \n5.6% \n5.3% \n4.5% \n4.2% \n1.6% \n0.8% 0.8% \n0.5%    \n   Lack of RSV knowledge and safety concerns were \namong the top reasons for not wanting an RSV vaccine \nCDC and University of Iowa/RAND survey, unpublished 41 \n     \n  \n     \n   Values \n\n–\n–Do older adults feel that the desirable effects of RSV vaccination are \nlar\nge relative to the undesirable effects? \n How d\no older adults view the balance of desirable versus \nun\ndesirable effects? \n Woul\nd older adults feel that the benefits outweigh the harms? \nNo Probably no Probably Yes Yes Varies Don’t know \n42 \n    \n  \n      \n \n  Values \nIs there important uncertainty about, or variability in, how much older \nad\nults value the main outcomes? \n– Is th\nere evidence that the variability is large enough to lead to \ndif\nferent decisions? \nImportant  uncertainty or variability \nProbably important  uncer tainty  or  variability \nProbably not important uncertainty or variability \nNo important uncertainty or variability \nNo known undesirable outcomes \n43 \n Acceptability \nWould recommending RSV vaccines for older adults be \nacceptable to key stakeholders? \n \n     \n   \n       \n     \n              \n  Vaccine Policy Collaborative Initiative \nSurvey of physicians, February–March 2017 \nNational network of 930 primary care physicians who agreed to \nparticipate in surveys about vaccine policy issues \n– 620 physicians (67%) completed the survey \n– Responses analyzed from 317 respondents (51%) who reported \ncaring for ≥1 adult patient with possible RSV in the preceding 12 \nmonths \nHurley LP , Allison MA, Kim L, et al. Primary care physicians’ perspectives on respiratory syncytial virus (RSV) disease in ad ults and a potential RSV vaccine for adults. 2019 Vaccine \n37(4): 565- 570. ISSN 0264- 410X. https://doi.org/10.1016/j.vaccine.2018.12.031 . 45 \nPhysician Perception of Importance of RSV as a pathogen in \nthe following groups of patients, United States, 2017 (n = 317) \nA majority of physicians believed \nthat RSV was a very important pathogen in adults of any age with an immunocompromising \ncondition (57%) and adults aged \n≥65 years with cardiopulmonary \ndisease (56%). \n              \n   \n  \n  \n \n   \n   \n       \nHurley LP , Allison MA, Kim L, et al. Primary care physicians’ perspectives on respiratory syncytial virus (RSV) disease in ad ults and a potential RSV vaccine for adults. 2019 Vaccine \n37(4): 565- 570. ISSN 0264- 410X. https://doi.org/10.1016/j.vaccine.2018.12.031. 46 \nPhysician Perception of Importance of RSV as a pathogen in \nthe \nfollowing groups of patients, United States, 2017 (n = 317) \nOne third of physicians believed \nthat RSV was a very important pathogen in adults 50–64 years \nwith cardiopulmonary disease \n(35%) and adults ≥65 years \nwithout cardiopulmonary \ndisease (31%). \n              \n   \n  \n  \n  \n \n  \n       \nHurley LP , Allison MA, Kim L, et al. Primary care physicians’ perspectives on respiratory syncytial virus (RSV) disease in ad ults and a potential RSV vaccine for adults. 2019 Vaccine \n37(4): 565- 570. ISSN 0264- 410X. https://doi.org/10.1016/j.vaccine.2018.12.031. 47 \n        \n \n  \n \n    Acceptability \nWould r ecommending RSV vaccines for adults aged ≥65 years be \nacceptable to key stakeholders? \n– Are th\nere key stakeholders that would not accept the distribution of \nbene\nfits and harms? \n– Are th\nere key stakeholders that would not accept the undesirable \neffects in the short term for the desirable effects (benefits) in the \nfu\nture? \nNo Probably No Probably Yes Yes Varies Don’t know \n48 \n  Feasibility \nIs RSV vaccination for older adults feasible to implement? \n  \n  \n   Barriers to implementation of a novel RSV vaccine may \ninclude: \nVaccine storage and handling requirements \nComplexity of the adult vaccination schedule (including coadministration) \nFinancial barriers \n50 \n51 \n \n \n       \n  \n \n     \n \n  \n   \n \n \n   \n  Storage & handling requirements \nGSK RSVpreF3 Pfizer RSVpreF \nSupplied as single dose Supplied as single dose, or as a 5-pack or \n10-pack of single- dose kits \nReconstitution required: single dose vial \nof lyophilized powder (antigen component) + single dose vial of liquid (adjuvant component) Reconstitution required: single dose vial of lyophilized powder, reconstitution supplies included in kit \nBoth components should be refrigerated (2–8°C) in original container, protected \nfrom light Product should be refrigerated (2–8° C) in \noriginal container, protected from light \nAfter reconstitution, the product should be administered within 4 hours, otherwise \ndiscarded After reconstitution, the product should be administered within 4 hours, otherwise \ndiscarded \n \n  \n     \n \n \n \n  \n      Older adult routine immunization schedule is \nbecoming more complex \nhttps://www.cdc.gov/vaccines/schedules/hcp/imz/adult.html \n50-64 years ≥65 years \nInfluenza \ninactivated (IIV4) or \nInfluenza recombinant (RIV4) 1 dose annually \nTetanus, diphtheria, pertussis \n(Tdap or Td) 1 dose Tdap, then Td or Tdap booster every 10 years \nZoster recombinant \n(RZV) 2 doses \nPneumococcal \n(PCV15, PCV20, \nPPSV23) 1 dose PCV15 followed by PPSV23 \nOR \n1 dose PCV20 ( see notes ) 1 dose PCV15 followed by PPSV23 \nOR \n1 dose PCV20 \nPotential fall or other regularly scheduled COVID -19 vaccine \nClinicians may face competing vaccine priorities 52 \n \n  \n       \n        Time/financial barriers \nOlder adults without health insurance coverage may experience financial \nhardship obtaining an RSV vaccine. \nFinancial hardship may also arise if vaccine recipients need to take time off \nfrom work to receive an RSV vaccine, or due to post-vaccination reactogenicity. \n53 \n     \n  \n    \n  Feasibility \nIs the GSK adjuvanted RSVpreF3 vaccine feasible to implement among \nadul\nts aged ≥65 years? \nIs th\ne Pfizer bivalent RSVpreF vaccine feasible to implement among adults \naged\n ≥65 years? \nNo Probably No Pr obably Yes Ye s Va ries Don’ t know \n54 \n  \n Resource Use \nIs an RSV vaccine program for older adults a reasonable and \nefficient allocation of resources? \n     \n    \n  \n    \n       \n     \n     \n      \n Work group considerations \nRSV vaccination for older adults could be a cost-effective intervention \nThere is substantial uncertainty in the net societal costs of an RSV \nvaccination program for older adults, driven by: \n– Uncertainty in incidence of severe RSV illness \n– Uncertainty in vaccine acquisition cost \n– Uncertainty in duration of protection from RSV vaccination \nNone of the three models incorporated medical costs of longer -term \nsequelae of RSV infection (e.g., admission to skilled nursing facilities) \nVaccination of older age groups would be more cost effective than vaccination of younger age groups \n56 \n       \n      \n \n    \n      \n Resource Use \n\nIs use of GSK a djuvanted RSVpreF3 vaccine among adults aged ≥65\nyea\nrs a reasonable and efficient allocation of resources, compared with\nno\n RSV vaccine?\nIs\n use of Pfizer bivalent RSVpreF vaccine among adults aged ≥65\nyears a reasonable and efficient allocation of resources, compared with\nno\n RSV vaccine?\nNo Probably No Prob ably Yes Yes Var ies Don’t kno w \n57 \n \n  Equity \nWhat would be the impact on health equity of recommending \nRSV vaccines in older adults? \n  \n      \n    Incidence of RSV \nhospitalization is higher among \npersons in low -\nincome ZIP codes \nZheng Z, et al. Estimated incidence of respiratory hospitalizations attributable to RSV infections across age and socioeconom ic groups. \nPneumonia (Nathan). 2022 Oct 25;14(1):6. doi: 10.1186/s41479- 022-00098 -x. 59 \n \n \n \n \n \n \n  \n   \n  Age of adults hospitalized with RSV, by race and \nethnicity, RSV -NET \nN Median age, years \n(interquartile range) \nAll 9,163 70 (58–81) \nRace and ethnicity \nWhite, non-Hispanic 5,596 73 (62–83) \nBlack, non-Hispanic 1,731 60 (50–70) \nHispanic 713 65 (50–77) \nAsian or Pacific Islander, non-Hispanic 518 77 (64–85) \nAmerican Indian or Alaska Native, non-Hispanic 56 57 (47–71) \nCDC RSV -NET data 2015–2020 (unpublished) 60 \n \n \n \n \n \n \n  \n   \n  Age of adults hospitalized with RSV, by race and \nethnicity, RSV -NET \nN Median age, years \n(interquartile range) \nAll 9,163 70 (58–81) \nRace and ethnicity \nWhite, non-Hispanic 5,596 73 (62–83) \nBlack, non-Hispanic 1,731 60 (50–70) \nHispanic 713 65 (50–77) \nAsian or Pacific Islander, non-Hispanic 518 77 (64–85) \nAmerican Indian or Alaska Native, non-Hispanic 56 57 (47–71) \nCDC RSV -NET data 2015–2020 (unpublished) 61 \n     \n       \n  \n \n  \n    \n   \n      \n    \n \n   \n  \n   Chronic medical conditions associated with increased risk of RSV disease \nare more prevalent in U.S. adults in certain demographic groups \nHeart failure Coronary heart \ndisease Diabetes mellitus COPD\na Asthma \nBlack, non-Hispanic\nb ↑c ↑↑c ↑c,d ↑e,f \nAI/ANg, non -\nHispanicb ↑↑h ↑↑h ↑e \nHispanica ↑c,d,h ↓e,f \nAsian, non -\nHispanicb ↓c ↓c ↑c,d ↓h ↓e \nLower income or SES\ni ↑j ↑h,j,k ↑h,l ↑h ↑e,f,h \na COPD = chronic obstructive pulmonary disease \nb Compared with non- Hispanic White adults \nc Tsao et al, Circulation (2022): https://doi.org/10.1161/cir.0000000000001052 \nd Cheng et al, JAMA (2019): https://doi.org/10.1001/jama.2019.19365 \ne https://www.cdc.gov/asthma/most_recent_national_asthma_data.htm \nf Bhan et al, Am J Public Health (2015): https://doi.org/10.2105/ajph.2014.302172 \ng AI/AN = American Indian or Alaska Native h NHIS 2018: https://www.cdc.gov/nchs/nhis/shs/tables.htm \ni SES = socio -economic status \nj Abdalla et al, JAMA Netw Open (2020): \nhttps://doi.org/10.1001%2Fjamanetworkopen.2020.18150 \nk Hamad et al, JAMA Cardiol (2020): https://doi.org/10.1001/jamacardio.2020.1458 \nl Beckles and Chou, MMWR (2016): http://dx.doi.org/10.15585/mmwr.mm6545a4 62 \n  \n \n  \n      Access to an RSV vaccine may be determined by health \ninsurance coverage \n0% 5% 10% 15% 20% \n55-64 ≥65 Percentage of U.S. \nadults without health \ninsurance \nAge group (years) American Indian or Alaska Native, \nnon-Hispanic \nHispanic \nBlack, non-Hispanic \nAsian, non-Hispanic \nWhite, non-Hispanic \nU.S. Census Bureau, 2021 American Community Survey 1- year estimates: https://data.census.gov/table 63 \n  \n          \n  \n  \n     Access to an RSV vaccine may be determined by health \ninsurance coverage \nAge group \n(years) Percentage of population without health insurance \nBelow \npoverty 1.0– 1.9x \npoverty 2.0– 2.9x \npoverty ≥3.0x poverty \n19–64 23.0% 22.2% 16.8% 6.5% \n≥65 2.3% 1.0% 0.9% 0.5% \nExample income for 2 -person household $18,145 $36,290 $54,435 \nwithout children, age <65 years \nU.S. Census Bureau, 2021 American Community Survey 1- year estimates: https://data.census.gov/table 64 \n     \n   Equity \nWhat would be the impact on health equity of recommending RSV\nvacc\nines in adults aged ≥65 years?\nReduced \nProbably reduced \nProbably no impact \nProbably increased \nIncreased \nVaries \nDon’t know \n65 \nSummary \n   \n    \n      \n    \n      \n     \n     \n    \n        \n    \n  \n   \n  Domain Question Work Group Judgements \nAdults aged ≥65 years GSK Pfizer \nPublic Health \nProblem Is RSV of public health importance? Yes \nBenefits and \nHarms How substantial are the desirable anticipated effects? Moderate – Large Moderate – Large \nHow substantial are the undesirable anticipated effects? Minimal – Small Minimal – Small \nDo the desirable effects outweigh the undesirable effects? Favors intervention Favors intervention \nWhat is the overall certainty of the evidence profile? Moderate Moderate \nValues Does the target population feel the desirable effects are large \nrelative to the undesirable effects? Yes/Probably yes \nIs there important variability in how patients value the outcomes? Important variability/Probably important variability \nAcceptability Is the intervention acceptable to key stakeholders? Yes/Probably yes \nFeasibility Is the intervention feasible to implement? Yes/Probably yes Yes/Probably yes \nResource Use Is the intervention a reasonable and efficient allocation of resources? Yes/Probably yes Yes/Probably yes \nEquity What would be the impact on health equity? Increased/Probably increased \n67 \n   \n    \n    \n   \n     \n     \n  \n     \n Work Group interpretation \nGSK’s adjuvanted RSVpreF3 and Pfizer’s bivalent RSVpreF vaccines both \nhave demonstrated significant efficacy against lower respiratory tract \nillness caused by RSV among older adults \n– Trials underpowered to show efficacy against RSV hospitalization \n– Groups at highest risk of severe RSV disease were under- represented in \nclinical trials \nAt least one case of inflammatory neuropathy has been observed among recipients of each investigational vaccine \nIf licensed, post licensure surveillance for both safety and vaccine \neffectiveness will be critical \n68 \n \n   \n  \n     \n   \n   \n     \n     \n   \n \n     \n   \n    \n   \n  \n      \n  \n      \n \n    \n   \n  \n  \n        \n          Choice of age threshold at which to recommend* RSV vaccines \nPros Cons \nAge ≥65 years • Greater risk of RSV disease and therefore \nmore favorable population- wide balance \nof risks and benefits of vaccination (in light of 1– 2 cases of inflammatory \nneuropathy observed) \n• Aligns with licensure for adjuvanted and high- dose influenza vaccines and age -\nbased pneumococcal vaccination • Lost opportunity to prevent additional disease in the 60–64 age group, who are \ndisproportionately from racial and ethnic groups impacted by RSV at earlier ages \nAge ≥60 years • Potential to prevent a greater total burden of disease (e.g., number of hospitalizations) \n• Increases access to adults 60 –64 with \nmedical risk factors for severe RSV disease (disproportionately in racial and ethnic groups impacted by RSV at earlier ages) • Uninsured adults would have difficulty obtaining vaccination (disproportionately aged 60–64 in racial, ethnic and socioeconomic \ngroups at greater risk) \n• May experience more difficulty achieving clinician adoption of the recommendation among patients 60–64 \n• Less efficient allocation of societal resources \n*FDA has not yet completed review of safety and efficacy data for the GSK RSVpreF3 vaccine and the Pfizer RSVpreF \nvaccine. ACIP recommendations would be made only if the vaccines are approved and licensed by the FDA. \n69 \n \n Evidence to Recommendations Framework \nSummary: Work Group Interpretations (GSK RSVpreF3) \n70 \n \n \n  \n \n  \n \n  \n \n  \n \n  \n \n  \n \n \n \n    \n  \n \n  \n \n  \n \n  \n \n  \n \n  \n \n \n \n    Evidence to Recommendations Framework \nSummary: Work Group Interpretations (GSK RSVpreF3) \nAmong adults aged ≥65 years: Minority opinion \nBalance of \nconsequences Undesirable \nconsequences \nclearly outweigh \ndesirable \nconsequences in \nmost settings Undesirable \nconsequences \nprobably \noutweigh \ndesirable \nconsequences in \nmost settings The balance \nbetween \ndesirable and \nundesirable \nconsequences is \nclosely balanced \nor uncertain Desirable \nconsequences \nprobably \noutweigh \nundesirable \nconsequences in \nmost settings Desirable \nconsequences \nclearly outweigh \nundesirable \nconsequences in \nmost settings There is \ninsufficient \nevidence to \ndetermine the \nbalance of \nconsequences \nAmong adults aged ≥60 years: \nBalance of \nconsequences Undesirable \nconsequences \nclearly outweigh \ndesirable \nconsequences in \nmost settings Undesirable \nconsequences \nprobably \noutweigh \ndesirable \nconsequences in \nmost settings The balance \nbetween \ndesirable and \nundesirable \nconsequences is \nclosely balanced \nor uncertain Desirable \nconsequences \nprobably \noutweigh \nundesirable \nconsequences in \nmost settings Desirable \nconsequences \nclearly outweigh \nundesirable \nconsequences in \nmost settings There is \ninsufficient \nevidence to \ndetermine the \nbalance of \nconsequences \n71 \n \n \n  \n  \n     \n \n  \n  \n     \n \n      Evidence to Recommendations Framework \nSummary: Work Group Interpretations (GSK RSVpreF3) \nType of recommendation, adults aged ≥65 years \nWe do not recommend the intervention \nWe recommend the intervention for individuals based on shared clinical decision -making \nWe recommend the intervention \nType of recommendation, adults aged ≥60 years* \nWe do not recommend the intervention \nWe recommend the intervention for individuals based on shared clinical decision -making \nWe recommend the intervention \n*Minority opinion: shared clinical decision -making for individual adults aged 60– 64 years \nMinority opinion 72 \n \n Evidence to Recommendations Framework \nSummary: Work Group Interpretations (Pfizer RSVpreF ) \n73 \n \n \n  \n \n  \n \n  \n \n  \n \n  \n \n  \n \n \n \n    \n  \n \n  \n \n  \n \n  \n \n  \n \n  \n \n \n \n    Evidence to Recommendations Framework \nSummary: Work Group Interpretations (Pfizer RSVpreF ) \nAmong adults aged ≥65 years: Minority opinion \nBalance of \nconsequences Undesirable \nconsequences \nclearly outweigh \ndesirable \nconsequences in \nmost settings Undesirable \nconsequences \nprobably \noutweigh \ndesirable \nconsequences in \nmost settings The balance \nbetween \ndesirable and \nundesirable \nconsequences is \nclosely balanced \nor uncertain Desirable \nconsequences \nprobably \noutweigh \nundesirable \nconsequences in \nmost settings Desirable \nconsequences \nclearly outweigh \nundesirable \nconsequences in \nmost settings There is \ninsufficient \nevidence to \ndetermine the \nbalance of \nconsequences \nAmong adults aged ≥60 years: \nBalance of \nconsequences Undesirable \nconsequences \nclearly outweigh \ndesirable \nconsequences in \nmost settings Undesirable \nconsequences \nprobably \noutweigh \ndesirable \nconsequences in \nmost settings The balance \nbetween \ndesirable and \nundesirable \nconsequences is \nclosely balanced \nor uncertain Desirable \nconsequences \nprobably \noutweigh \nundesirable \nconsequences in \nmost settings Desirable \nconsequences \nclearly outweigh \nundesirable \nconsequences in \nmost settings There is \ninsufficient \nevidence to \ndetermine the \nbalance of \nconsequences \n74 \n \n \n  \n  \n     \n \n  \n  \n     \n \n      Evidence to Recommendations Framework \nSummary: Work Group Interpretations (Pfizer RSVpreF ) \nType of recommendation, adults aged ≥65 years \nWe do not recommend the intervention \nWe recommend the intervention for individuals based on shared clinical decision -making \nWe recommend the intervention \nType of recommendation, adults aged ≥60 years* \nWe do not recommend the intervention \nWe recommend the intervention for individuals based on shared clinical decision -making \nWe recommend the intervention \n*Minority opinion: shared clinical decision -making for individual adults aged 60– 64 years \nMinority opinion 75 \n Acknowledgements \n Doug Campos -Outcalt \n Katherine Fleming-Dutra \n Monica Godfrey \n Fiona Havers \n Anne Hause \n Jefferson Jones \n Megan Lindley \n Meredith McMorrow \n Rebecca Morgan \n Neil Murthy \n Sara Oliver \n Christine Olson \n Ismael Ortega Sanchez  David Shay \n Amanda Payne \n Huong Pham \n Jamison Pike \n Tamara Pilishvili \n Mila Prill \n Lauren Roper \n Diya Surie \n Christopher Taylor \n Evelyn Twentyman \n Megan Wallace \n Michael Whitaker \n Patricia Wodi 76 \n     \n \n     \n \n      \n \n      \n Policy questions for ACIP \nShould vaccination with GSK RSVpreF3 vaccine (120µg antigen + AS01E adjuvant, 1 \ndose IM), rather than no vaccine, be recommended in persons aged ≥65 years? \nShould vaccination with GSK RSVpreF3 vaccine (120µg antigen + AS01E adjuvant, 1 \ndose IM), rather than no vaccine, be recommended in persons aged ≥60 years? \nShould vaccination with Pfizer bivalent RSVpreF vaccine (120µg antigen, 1 dose IM), \nrather than no vaccine, be recommended in persons aged ≥65 years? \nShould vaccination with Pfizer bivalent RSVpreF vaccine (120µg antigen, 1 dose IM), \nrather than no vaccine, be recommended in persons aged ≥60 years? \n \n    \n        \n   For more information, contact CDC \n1-800-CDC- INFO (232- 4636) \nTTY:  1 -888- 232-6348 www.cdc.gov \nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.", "summary": "Centers for Disease Control and Prevention  Evidence to  Recommendations Framework  Respiratory  Syncytial Virus (RSV) in  Adults  GSK adjuvanted RSVpreF3 vaccine in older adults  Pfizer bivalent RSVpreF vaccine in older adults  Michael Melgar, MD  Lead, Adult RSV ACIP Work Group ACIP Meeting February 23, 2023                           Evidence to Recommendations (EtR ) Framework Poli cy Questions  Should vaccination with GSK RSVpreF3 vaccine (120µg antigen + AS01E adjuvant, 1  dose IM),…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/RSV-Adults-04-Melgar-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 78}
{"title": "RSV Adults 05 Melgar 508", "content": "•\n•\n•\n•\n \n    \n        \n   For more information, contact CDC \n1-800-CDC- INFO (232- 4636) \nTTY:  1 -888- 232-6348 www.cdc.gov \nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.", "summary": "• • • •                    For more information, contact CDC  1-800-CDC- INFO (232- 4636)  TTY:  1 -888- 232-6348 www.cdc.gov  The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/RSV-Adults-05-Melgar-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 2}
{"title": "Chikungunya 01 Bell 508", "content": "CHIKUNGUNYA VACCINES\nBeth Bell, MD, MPH\nChair, ACIP Chikungunya Vaccines Work GroupACIP Meeting\nFebruary 23, 2023\nBackground\nValneva completed submission of Biologics License Application (BLA) for \ntheir chikungunya vaccine to FDA in December 2022\nNo chikungunya vaccine ever licensed in United States or globally\nNo existing ACIP chikungunya vaccine recommendations\nChikungunya Vaccines Work Group formed in May 2022 to develop policy options for ACIP’s consideration for use of chikungunya vaccine among U.S. \npersons at risk of chikungunya, including \n–Travelers\n–Residents of U.S. territories and states with, or at risk of, transmission\n–Laboratory workers\nTerms of Reference for Chikungunya Vaccines Work Group \nTo review information on chikungunya disease, including outcomes\nTo review data on chikungunya epidemiology and burden among U.S. residents, \nincluding travelers and persons living in areas at risk for local transmission\nTo review data on safety, immunogenicity, and effectiveness of chikungunya \nvaccines \nTo provide evidence -based recommendation options for ACIP\nTo identify areas in need of further research for informing potential future vaccine recommendations\nTo publish a chikungunya vaccine MMWR Recommendations and Reports document\nACIP Ex Officio Invited Consultants\nBeth Bell, Univ Washington (Chair) Robin Levis, FDA Alan Barrett, Univ Texas Galveston\nWilbur Chen, Univ Maryland Sixun Yang, FDA Carina Blackmore, Florida Dept Health\nLesley Dupuy, NIH Alan Lam, DoD\nCDC Leads Margaret Ryan, DoD\nSusan Hills, DVBD (Lead) ACIP Liaisons Steven Schofield, CATMAT\nNicole Lindsey, DVBD (Deputy Lead) Paschal Apanga, AIM David Shlim, Jackson Hole Travel & Trop Med\nElizabeth Barnett, ISTM Nestor Sosa, Uni New Mexico Hospital\nJames Campbell, AAP Sanet Torres, San Jorge Children & Women's Hospital\nMary Pat Friedlander, AAFP Kirsten Vannice, Bill & Melinda Gates Foundation\nMary Wilson, Univ California San FranciscoChikungunya Vaccines Work Group members\nDVBD DGMQ ISD\nErin Staples Sarah Guagliardo Elisabeth Velazque z\nAnn Powers\nLaura Adams DHQP GRADE/ETR consultants\nJoshua Wong Michael McNeil Doug Campos -Outcalt\nRebecca Morgan\nNCEZID GID\nRita Helfand Rebecca Casey ACIP Secretariat\nJessica MacNeil, NCIRD\nLeslie Lee, NCIRDChikungunya Vaccines Work Group CDC participants\nRecap of previous Work Group presentations to ACIP \nOctober 2022\n–Overview of chikungunya virus disease and vaccines\n–Immunogenicity and safety of Valneva’s chikungunya vaccine\nOverview of today’s session\nGlobal epidemiology of chikungunya\n–Dr. Susan Hills (CDC/NCEZID)\nChikungunya in U.S. travelers\n–Ms. Nicole Lindsey (CDC/NCEZID)\nPersistent arthralgia following chikungunya\n–Ms. Nicole Lindsey (CDC/NCEZID)\nWork Group considerations\n–Ms. Nicole Lindsey (CDC/NCEZID)", "summary": "CHIKUNGUNYA VACCINES Beth Bell, MD, MPH Chair, ACIP Chikungunya Vaccines Work GroupACIP Meeting February 23, 2023 Background Valneva completed submission of Biologics License Application (BLA) for  their chikungunya vaccine to FDA in December 2022 No chikungunya vaccine ever licensed in United States or globally No existing ACIP chikungunya vaccine recommendations Chikungunya Vaccines Work Group formed in May 2022 to develop policy options for ACIP’s consideration for use of chikungunya…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/Chikungunya-01-Bell-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 7}
{"title": "Chikungunya 02 Hills 508", "content": "National Center for Emerging and Zoonotic Infectious Diseases\nGLOBAL EPIDEMIOLOGY OF \nCHIKUNGUNYA\nSusan Hills, MBBS, MTH\nCDC Lead , Chikungunya Vaccines Work Group\nArboviral Diseases Branch\nDivision of Vector -Borne Diseases\nFort Collins, Colorado\nACIP meeting, February 23, 2023\nChikungunya\nMosquito -b orne viral disease\n–Primarily human -mo squito -human transmission\n–Mainly A edes aegypti and Aedes albopictus\nClinically characterized by acute onset of fever and \noft\nen severe polyarthralgia\nRisk factors for severe disease\n–Age >65 years\n–Underlying medical conditions\n–Neonate infected through intrapartum transmission \nSource: PAHO, 2011. www.paho.org\nSpread of chikungunya virus into new regions, 2004 -2015\nZeller et al, Int J Infect Dis, 2016\nSpread of chikungunya virus into new regions, 2004 -2015\nZeller et al, Int J Infect Dis, 2016\nChikungunya cases reported in the Americas, 2013 -2022\n02000004000006000008000001000000\n2013 2014 2015 2016 2017 2018 2019 2020 2021 2022\nCountries and territories with past or current \ntransmission of chikungunya virus, 2023\nhttps://www.cdc.gov/chikungunya/geo/index.html\n\nLimited data sources for understanding current \npatterns of chikungunya virus transmission\nWHO\nwebsites\nMinistry of \nHealth websites\nCases among \ntravelers\nGeneral features of chikungunya virus transmission\nOccurs in tropical and subtropical regions\n–Rare outbreaks in temperate areas\nOften seen in areas with similar vector- borne diseases (e.g., dengue, Zika)\nTransmission impacted by several factors including weather, environmental \nfactors, pre -existing population immunity, population density, local vectors \nPatterns for chikungunya virus transmission vary\nOngoing low -level transmission with periodic outbreak activity in Africa, \nAsia, Central America, and South America\n–Immunologically susceptible individuals continue to acquire infection and \npropagate human -mosquito -human cycles\n–Outbreaks are unpredictable in terms of timing and size\nCessation of transmission after outbreaks is common in island nations\n–Apparent interruption in Pacific Island and most of Caribbean countries and territories\n–Risk for reintroduction will increase over time as population immunity decreases\nFeatures of chikungunya outbreaks\nMore likely in regions \nwith no\n or mild \noutbreaks in recent past\nCan be localized or w\nidespreadOften rapid increase in size\n30%– 6 0% population infected within few months\nHuge outbreaks, like 2014 –\n2\n016 in Americas, unlikely in \nfuture\nContinued reporting of large o\nutbreaks likelyMany commence during tr\nopical rainy season\nCan occur in dry season\nPeriod of intense tr\nansmission typically \nshort, often 3 –6 months\nInterval between outbreaks\nUnpredictable and variable, can be >20 years\nRelated to factors including pre -existing population immunity, build -up \nof non -immune population, environmental factors\nSome countries report outbreaks regularly, but typically in different \nlocations\nSummary\nMainly tropical and subtropical areas\nCurrently, most countries with chikungunya virus activity have low -level \ntransmission \nOutbreak- prone disease \nImportant impact when outbreaks occur as often intense, although \ngenerally short -lived, transmission", "summary": "National Center for Emerging and Zoonotic Infectious Diseases GLOBAL EPIDEMIOLOGY OF  CHIKUNGUNYA Susan Hills, MBBS, MTH CDC Lead , Chikungunya Vaccines Work Group Arboviral Diseases Branch Division of Vector -Borne Diseases Fort Collins, Colorado ACIP meeting, February 23, 2023 Chikungunya Mosquito -b orne viral disease –Primarily human -mo squito -human transmission –Mainly A edes aegypti and Aedes albopictus Clinically characterized by acute onset of fever and  oft en severe…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/Chikungunya-02-Hills-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 12}
{"title": "Chikungunya 03 Lindsey 508", "content": "National Center for Emerging and Zoonotic Infectious Diseases\nChikungunya in US travelers\nNicole Lindsey, MS\nCDC Deputy Lead , Chikungunya Vaccines Work Group\nArboviral Diseases Branch\nCenters for Disease Control and Prevention\nNational surveillance data for chikungunya virus disease \nin US travelers\nData presented include confirmed and probable cases in residents of US \nstates reported to CDC (excludes US territories and associated states) \nPrior to 2006, very rarely identified in US travelers; data are included from 2006– 2021\n–Not nationally -notifiable from 2006 –2014\nFrom 2006– 2021, 4,590 cases in US travelers reported to CDC\nChikungunya virus disease cases in US travelers, \n2006 –2021 (N=4,590)\n9 13 0 2 11 1 2 162,831\n923\n250156 116192\n32 36\n05001,0001,5002,0002,5003,000\n2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021Number of cases\nSex of travel- associated chikungunya cases, \n2006 –2021 (N=4,590) \nSex No. (%)\nMale 1,614 (35%)\nFemale 2,973 (65%)\n3 cases unreported sex\nAge of travel- associated chikungunya cases, \n2006 –2021 (N=4,590) \nYears No. (%)\n0–19 445 (10%)\n20–39 1,166 (25%)\n40–59 1,927 (42%)\n60–79 952 (21%)\n80+ 86 (2%)\n14 cases unreported age\nMonth of onset of travel- associated chikungunya cases, \n2006 –2021 (N=4,590)\n0100200300400500600700800900\nJan Feb Mar Apr May Jun Jul Aug Sep Oct Nov DecNumber of cases\nMonth of illness onset\nMonth of onset of travel- associated chikungunya cases, \n2006 –2021 (N=4,590)\n0100200300400500600\nJan Feb Mar Apr May Jun Jul Aug Sep Oct Nov DecNumber of cases\nMonth of illness onset2014\nAll other years\nOutcomes of travel- associated chikungunya \ncases, 2006 –2021 (N=4,590) \nOutcome No. (%)\nHospitalized 834 (18%)\nDied* 4(0.1%)\n*Cause of death unknown: All aged 63 –84 years and died 36 –61 days after illness onset\nHospitalization rates by age among travel- associated \nchikungunya cases, 2006 –2021 (N=4,590)\n14 cases unreported ageAge (years) No. Hospitalized (%)\n0–1 17 7(41%)\n2–9 101 31 (31%)\n10–19 327 60 (18%)\n20–39 1,166 192 (16%)\n40–59 1,927 295 (15%)\n60–79 952 220 (23%)\n80+ 86 33 (38%)\nRegions of probable acquisition of travel- associated \nchikungunya, 2006 –2021 (N=4,590)\n95 cases unknown location of infection2,4946705663542936156\n0 500 1,000 1,500 2,000 2,500 3,000CaribbeanCentral AmericaAsiaSouth AmericaNorth AmericaAfricaOceania/Pacific\nNumber of cases\nRegions of probable acquisition of travel- associated \nchikungunya, 2017 –2021 (N=532)\n25cases unknown location of infection44253174333423\n0 50 100 150 200 250 300 350CaribbeanCentral AmericaAsiaSouth AmericaNorth AmericaAfricaOceania/Pacific\nNumber of cases\nMost common locations of probable acquisition of \ntravel -associated chikungunya, 2006 –2021 (N=4,590)\n95 cases unknown location of infection1,01649946039729326625914213596\n0 200 400 600 800 1,000 1,200Dominican RepublicPuerto RicoHaitiIndiaMexicoJamaicaEl SalvadorGuatemalaNicaraguaHonduras\nMost common locations of probable acquisition of \ntravel -associated chikungunya, 2017 –2021 (N=532)\n25cases unknown location of infection199333328242311109\n0 50 100 150 200 250IndiaBangladeshMexicoBrazilPhilippinesThailandPakistanPuerto RicoMyanmar\nLimitations of national surveillance data\nReported cases likely underestimate true incidence of chikungunya \ndisease among travelers\nReported cases likely represent higher proportion of severe outcomes\nComplete data often unavailable, particularly for travel history\n–No information on duration of travel or activities during travel\nNo information on duration of symptoms or long -term sequalae\nSummary\nRelatively few traveler cases reported annually except during time of large \noutbreaks in Americas \nReported cases likely underestimate true incidence but overestimate proportions of severe outcomes\nVery young children and older adults have highest hospitalization rates\nCases have occurred among travelers to all regions with chikungunya risk and can occur year -round\n–Case numbers reflect level of chikungunya virus activity in, and number of \ntravelers to, destinations with risk", "summary": "National Center for Emerging and Zoonotic Infectious Diseases Chikungunya in US travelers Nicole Lindsey, MS CDC Deputy Lead , Chikungunya Vaccines Work Group Arboviral Diseases Branch Centers for Disease Control and Prevention National surveillance data for chikungunya virus disease  in US travelers Data presented include confirmed and probable cases in residents of US  states reported to CDC (excludes US territories and associated states)  Prior to 2006, very rarely identified in US…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/Chikungunya-03-Lindsey-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 15}
{"title": "Chikungunya 04 Lindsey 508", "content": "National Center for Emerging and Zoonotic Infectious Diseases\nChronic arthralgia after chikungunya\nNicole Lindsey, MS\nCDC Deputy Lead , Chikungunya Vaccines Work Group\nArboviral Diseases Branch\nCenters for Disease Control and Prevention\nClinical outcomes of chikungunya virus disease\nAcute symptoms typically resolve in 7 -10 days\nMortality is very rare\nSignificant proportion of patients have continued or recurrent arthralgia in \nmonths and years following acute illness\nAdditional long- term complications reported less frequently\n–Fatigue\n–Depression\n–Alopecia−Impaired memory\n−Sleep disorders\n−Lowered quality of life\nChronic joint symptoms after chikungunya\nMany published studies with high variability in results based on:\n–Study methodology\n–Definitions and ascertainment of symptoms\n–Duration of follow up\n–Characteristics of patient cohort (e.g., location, demographics)\nPrevious meta -analyses with varying outcomes and inclusion criteria\n–None used outcome and criteria most of interest to guide vaccine \nrecommendation process\nSystematic review and meta -analysis\nObjective to estimate percentage of patients with chronic arthralgia (≥3 \nmonths) following chikungunya virus infection\nLiterature search for articles published Jan 1, 2000 –Oct 24, 2022, \ndescribing primary data on arthralgia following chikungunya infection\nExcluded articles:\n–Without laboratory confirmation of all infections \n–Specific subgroups (e.g., children, people with co -infections, large \nproportion of cases hospitalized for acute disease)\n–Non -English language\nStudy selection process\n1,167•\n•\n••••Articles identified through search. All ab stracts reviewed1,087 did not meet criteria and were excluded\n80Articles with a full text review53 did not meet criteria and were excluded\n27Articles met inclusion criteriaS tandardized data extraction into spreadsheet tool\nCharacteristics of 27 included studies (N=4,079)\nMost clustered in 1 of 2 time periods (2005– 2006 and 2014– 2015)\n23 communities with outbreaks, 4 travelers to outbreak locations\n14 locations in Americas, 8 Indian Ocean, 4 Asia, 1 Europe\n4 studies included control group of non- infected persons\nRange of severity of illnesses (0 –33% hospitalized) \nVaried demographics of included participants\nChronic arthralgia following chikungunya virus disease*\n0%10%20%30%40%50%60%70%80%90%100%\n0 3 6 9 12 15 18 21 24 27 30 33 36Percentage with chronic arthralgia\nMonths after illness onset\n*Some studies estimated proportion with chronic arthralgia at >1 time point\nChronic arthralgia following chikungunya virus disease*\n0%10%20%30%40%50%60%70%80%90%100%\n0 3 6 9 12 15 18 21 24 27 30 33 36Percentage with chronic arthralgia\nMonths after illness onset\n*Some studies estimated proportion with chronic arthralgia at >1 time point\n7 studies included accounting for a total of 733 patients\nAll included patients who sought healthcare \nTwo traveler cohorts and five cohorts from communities with outbreaks\n–Travelers to countries in Indian Ocean and Americas\n–Outbreaks: Brazil, French Guiana, Martinique, Sint Maarten, Thailand\nPredominance of females (range 52– 74%)\nRange of study mean/median ages (35– 51 years)\nRange of severity (hospitalization range 0 –17%)Arthralgia 3 months after chikungunya infection \nArthralgia 3 months after chikungunya infection (N=7)\nStudy Location Sample Rate (95% CI )\nBocanegra 2016 Travelers to the Americas, 2014 -2015 34 50% (33, 67)\nSimon 2007 Travelers to the Indian Ocean, 2005 -2006 47 86% (75, 95)\nBertolotti 2020 Martinique, 2014 167 55% (48, 62)\nBenjamanukul 2021 Thailand, 2018 164 53% (46, 60)\nPeters 2018 Sint Marteen, 2014 56 52% (39, 64)\nSilva 2021 Brazil, 2014 -2016 153 43% (36, 50)\nBonifay 2018 French Guiana, 2014 112 42% (33, 51)\nSummary estimate* 51% (44, 58)\n0 20 40 60 80 100\n*Random effects model\nArthralgia 6 months after chikungunya infection\n9 studies included accounting for a total of 961 patients\nAll included patients who sought healthcare \nThree traveler cohorts and six cohorts from communities with outbreaks\n–Travelers to countries in Indian Ocean\n–Outbreaks: Bangladesh, French Guiana, Martinique, Mexico, \nSuriname, Thailand\nPredominance of females (range 52– 68%)\nRange of study mean/median ages (32– 60 years)\nRange of severity (hospitalization range 0 –33%)\nArthralgia 6 months after chikungunya infection (N=9)\nStudy Location Sample Rate (95% CI )\nSchilte 2013 Reunion Island, 2005 -2006 180 70% (63, 77)\nSimon 2007 Travelers to Indian Ocean, 2005 -2006 47 48% (35, 63)\nFeldstein 2017 USVI, 2014- 2015 165 44% (37, 52)\nMurillo -Zamora 2017 Mexico, 2015 136 42% (34, 50)\nBertolotti 2020 Martinique, 2014 167 36% (29, 43)\nBonifay 2018 French Guiana, 2014 112 31% (23, 40)\nvan Genderen 2016 Suriname, 2013 90 22% (14, 31)\nTaubitz 2007 Travelers to Indian Ocean, 2006 16 13% (0, 29)\nAnwar 2020 Bangladesh, 2017 48 13% (0, 22)\nSummary estimate* 35% (24, 47)\n*Random effects model 0 20 40 60 80 100\nArthralgia 12 months after chikungunya infection\n10 studies included accounting for a total of 1,539 patients\n9 included patients who sought healthcare; 1 population- based sample\nAll cohorts from communities with outbreaks: Aruba, Bangladesh, Brazil, \nGrenada, Italy, Malaysia, Martinique, Reunion Island, US Virgin Islands (2)\nPredominance of females (range 52– 73%)\nRange of study mean/median ages (33– 60 years)\nRange of severity (hospitalization range 0 –23%)\nArthralgia 12 months after chikungunya infection (N=10)\n*Random effects modelStudy Location Sample Rate (95% CI )\nde Moraes 2020 Brazil, 2016 -2018 107 61% (52, 70)\nMoro 2012 Italy, 2007 250 61% (55, 67)\nSchilte 2013 Reunion Island, 2005 -2006 180 58% (51, 65)\nHeath 2018 Grenada, 2014 240 35% (29, 41)\nFeldstein 2017 USVI, 2014- 2015 165 33% (26, 40)\nBertolotti 2020 Martinique, 2014 167 31% (24, 38)\nHennessey 2018 USVI, 2014- 2015 171 31% (24, 38)\nHuits 2018 Aruba, 2014 171 26% (19, 32)\nMohd Zim 2013 Malaysia, 2008 40 23% (10, 35)\nAnwar 2020 Bangladesh, 2017 48 19% (8, 30)\nSummary estimate* 38% (29, 46)\n0 20 40 60 80 100\nChronic arthralgia following chikungunya virus disease*\n*Among 9 studies that estimated proportion with chronic arthralgia at >1 time point0%10%20%30%40%50%60%70%80%90%100%\n0 3 6 9 12 15 18 21 24 27 30 33 36\nChronic arthralgia estimates among travelers (N=4)\nReference Location, Year N Population description 3m 6m 24m\nSimon 2007 Indian Ocean, 2005 -2006 47French travelers treated at \nLavaren Hospital in Marseilles 86% 48%\nLarrieu 2010 Indian Ocean, 2005 -2006 29French travelers treated at \nUniversity Hospital in Bordeaux 59%\nTaubitz 2007 Indian Ocean, 2006 16German travelers treated at Institute of Trop Med in Hamburg 13%\nBocanegra 2016 Americas, 2014- 2015 34Spanish travelers who presented to public health 50%\nLimitations\nVariability in case definitions, populations included, findings\nAlmost all persons who seek healthcare for symptoms; not representative \nof all cases\nVery few studies included control group to account for background rates of arthralgia in population\n–Crude estimates from all studies used to calculate summary estimates\nChronic arthralgia in controlled studies\nSoumahoro 2009 ( Reunion 2005- 2006)\n–199 CHIKV+,  199 CHIKV-\n–At 17m, CHIKV+ more joint pain than CHIKV -(53% vs 28%)\n–Estimated 47% (95% CI 37% –55%) of pain in case -patients attributed to CHIK\nGerardin 2011 ( Reunion 2005- 2006)\n–512 CHIKV+, 582 CHIKV-\n–At 16m, CHIKV+ more likely to complain of musculoskeletal pain (43% vs 17%) \n–Estimated 60% (95% CI 52% -68%) of pain in case -patients attributed to CHIK\nChronic arthralgia in controlled studies (cont.)\nFeldstein 2017 ( USVI 2014- 2015)\n–165 CHIKV+, 167 CHIKV-\n–At 6m, difference in arthralgia between case -patients and controls 32% (95% \nCI 24% –40%) after adjusting for age, sex, history of arthritis\n–At 12m, adjusted difference was 19% (95% CI 11% –28%)\nHennessey 2018 (USVI 2014- 2015)\n–171 CHIKV+, 338 CHIKV-\n–At 12m, 31% case -patients, 26% of controls joint pain in last week\n–Estimated 23% (95% CI 9% -37%) of continued joint pain in case -patients \nattributed to CHIK infection\nReview of key points\nA substantial proportion of patients who seek care for their acute illness have \nchronic arthralgia following chikungunya virus infection\n–Estimated ~one -half have arthralgia at 3 months\n–Rates decrease and ~one -third estimated with arthralgia at 12 months\nAll proportions likely overestimates of chronic arthralgia in patients overall as \nstudies:\n–Almost exclusively included persons who sought health care (i.e., likely more severe disease)\n–Do not account for background rate of arthralgia in population\nSummary\nDifficult to provide precise estimate of incidence of long- term joint pain \nafter chikungunya\nPercentages with long -term joint pain likely variable based on severity of \nacute illness, age, sex, comorbidities\nLong -term joint pain important complication of chikungunya that could be \nprevented by vaccination", "summary": "National Center for Emerging and Zoonotic Infectious Diseases Chronic arthralgia after chikungunya Nicole Lindsey, MS CDC Deputy Lead , Chikungunya Vaccines Work Group Arboviral Diseases Branch Centers for Disease Control and Prevention Clinical outcomes of chikungunya virus disease Acute symptoms typically resolve in 7 -10 days Mortality is very rare Significant proportion of patients have continued or recurrent arthralgia in  months and years following acute illness Additional long- term…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/Chikungunya-04-Lindsey-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 21}
{"title": "Chikungunya 05 Lindsey 508", "content": "National Center for Emerging and Zoonotic Infectious Diseases\nWORK GROUP PLANS AND TIMELINES\nNicole Lindsey, MS\nCDC Deputy Lead , Chikungunya Vaccines Work Group\nArboviral Diseases Branch\nCenters for Disease Control and Prevention\nACIP meeting\nFebruary 23, 2023\nWork Group timeline (tentative)\nDec Jan Feb Mar Apr May Jun Jul Aug Sept Oct Nov Dec Jan Feb Mar Apr2024\n(Today) Global    \nepidemiology, US traveler, and chronic arthralgia dataPresent EtR to \nACIPPresent to ACIP            other data relevant to recommendations ACIP vote on vaccine recommendations for adult travelers and laboratory workersBLA \nsubmission completed2023\nFDA determination on priority review Possible licensure\n\nSummary of Work Group plans and activities\nComprehensive review of immunogenicity and safety data (GRADE)\nFuture presentations to ACIP on topics relevant to consideration of vaccine \nuse in U.S. territories and states with risk of transmission\nOver longer term, additional vaccine data in younger age groups and/or additional chikungunya vaccines\nThank you", "summary": "National Center for Emerging and Zoonotic Infectious Diseases WORK GROUP PLANS AND TIMELINES Nicole Lindsey, MS CDC Deputy Lead , Chikungunya Vaccines Work Group Arboviral Diseases Branch Centers for Disease Control and Prevention ACIP meeting February 23, 2023 Work Group timeline (tentative) Dec Jan Feb Mar Apr May Jun Jul Aug Sept Oct Nov Dec Jan Feb Mar Apr2024 (Today) Global     epidemiology, US traveler, and chronic arthralgia dataPresent EtR to  ACIPPresent to ACIP            other data…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/Chikungunya-05-Lindsey-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 4}
{"title": "Dengue 01 Chen 508", "content": "AA ACC CII IPP PDD Dee enn ngg guu uee eVV Vaa acc ccc cii inn nee e\nWW Woo orr rkk kgg grr roo ouu upp pACIP Dengue Vaccine \nWorkgroup \nWilbur Chen, MD, MSc \nACIP Member and Workgroup Chair \nAdvisory Committee on Immunization Practices \nACIP Meeting February 23, 2023 \n   \n   \n   \n      \n      \n \n     \n   Dengue Virus \n DENV-1, 2, 3, 4 \n• Lifelong DENV type-specific \nimmunity \n• Short-term cross-immunity (~1–2 years) \n• A second dengue infection is the most important risk factor for severe dengue \n Dengue is the most common \nmosquito-borne virus globally \n\n      \n     \n   \n       \n       \n       \n      \n       \n    Dengvaxia™ \nan d previou  s \ndengue  \ninfection Clinical trials found different outcomes after \nDengvaxia™ vaccination among children with and \nwithout previous dengue infection. \n• Children without previous dengue infection had a \nhigher risk hospitalization and severe dengue if they \nwere vaccinated and then had a DENV infection. \n• Children with previous dengue infection were \nprotected from hospitalization and severe dengue if \nthey were vaccinated with Dengvaxia™. \n   \n      \n      \n       \n        \n    \n  \n   Dengvaxia™ ACIP Recommendation June 2021 \nThree doses of Dengvaxia are indicated \nfor the prevention of dengue disease \ncaused by dengue virus serotypes 1, 2, \n3, and 4 in people 9–16 years old with: \n• laboratory confirmation of previous \ndengue virus infection \nAND \n• living in endemic areas. \n\n     \n  \n    \n       \n    \n  Work group timeline 2023 for TAK003 \nPresentations to ACIP \nFeb March April May June July Aug Sept Oct Nov \nVaccine efficacy, immunogenicity, and \nsafety data and WG Interpretation GRADE analysis and cost -\neffectiveness analysis EtR, draft recommendations, \nand ACIP vote \n      \n       \n     \n      Summary of work group plans and activities \n• Review of efficacy, immunogenicity, and safety data (GRADE) \n• Review of EtR domains and cost-effectiveness analysis \n• Presentation of policy options and ACIP vote \n \n    \n  \n      \n     \n     Presentations today \nTAK-003 Efficacy, Safety and Immunogenicity Data \nDr. Shibadas Biswal, Takeda \nWork Group Summary and Interpretation of TAK-\n003 Efficacy, Safety, and Immunogenicity Data \nDr. Gabriela Paz-Bailey, CDC, NCEZID, DVBD \n            \n \n  \n \n \n \n \n \n \n  \n  \n  \n   \n  \n  \n  \n  \n \n \n \n \n \n \n \n  \n \n \n \n \n \n \n \n \n \n \n AA ACC CII IPP PDD Dee enn ngg guu uee eVV Vaa acc ccc cii inn nee ess sWW Woo orr rkk kgg grr roo ouu upp p ACIP Dengue Vaccines Workgroup \nACIP Members \nWilbur Chen (Chair) \nKathy Poehling \nBeth Bell \nVeronica McNally \nCDC Co-Lead \nGabriela Paz-Bailey Laura Adams \nEx Officio Members \nKaitlyn Morabito (NIH) \nRalph LeBlanc (FDA) \nIhid Carneiro Leao (FDA) \nKirk Prutzman (FDA) Srihari Seshadri (DOD) Liaison Representatives Elizabeth Barnett (AAP) \nRob Schechter (AIM) \nConsultants \nEdwin Asturias Robert Atmar \nAlan Barrett \nIris Cardona \nAnna Durbin \nTony Marfin Kristen Pierce \nAnita Shet CDC Contributors \nJosh Wong \nMimi Eckert \nRachel Eidex \nAlfonso Hernandez \nSusan Hills Terri Hyde \nMike McNeil \nJorge Munoz \nErin Staples \nCindy Weinbaum Rita Helfand", "summary": "AA ACC CII IPP PDD Dee enn ngg guu uee eVV Vaa acc ccc cii inn nee e WW Woo orr rkk kgg grr roo ouu upp pACIP Dengue Vaccine  Workgroup  Wilbur Chen, MD, MSc  ACIP Member and Workgroup Chair  Advisory Committee on Immunization Practices  ACIP Meeting February 23, 2023                                       Dengue Virus   DENV-1, 2, 3, 4  • Lifelong DENV type-specific  immunity  • Short-term cross-immunity (~1–2 years)  • A second dengue infection is the most important risk factor for severe…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/Dengue-01-Chen-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 8}
{"title": "03 COVID Wallace 508", "content": "Centers for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nCOVID -19 Vaccine Policy and Next Steps\nOctober 26, 2023\nMegan Wallace, DrPH, MPH\nCOVID -19 Epidemiology\n3Trends in weighted variant proportion estimates and Nowcast –\nUnited States, June 25 –October 14, 2023\nPI=Prediction Interval\nSource: https://covid.cdc.gov/covid -data -tracker/#variant -proportions\n\nWeekly population -based rates of COVID -19-associated hospitalizations by \nseason–COVID -NET, United States, March 2020 –September 2023\nSource: Coronavirus Disease 2019 (COVID -19) Hospitalization Surveillance Network (COVID -NET); https://www.cdc.gov/coronavirus/2019 -\nncov/covidnetdashboard/de/powerbi/dashboard.html . Accessed October 16, 2023.\nOct Nov Dec Jan Feb Mar Apr May June July Aug SepHospitalizations per 100,000\n010203040\nSurveillance Month\n2020 -20212019 -2020\n2021 -2022\n2022 -2023\n4\n5Weekly population -based rates of COVID -19-associated hospitalizations by \nage group –COVID -NET , United States, October 2022 –September 2023\nSource: Coronavirus Disease 2019 (COVID -19) Hospitalization Surveillance Network (COVID -NET); https://www.cdc.gov/coronavirus/2019 -\nncov/covidnetdashboard/de/powerbi/dashboard.html . Accessed October 16, 2023.\nOct Nov Dec Jan Feb Mar Apr May June July Aug Sep\nSurveillance MonthHospitalizations per 100,000\n010203060\n50\n405-17 years0-4 years\n18-49 years\n50-64 years\n≥65 years\n\n6Weekly COVID -19 new hospital admissions –National Healthcare Safety \nNetwork (NHSN), United States, August 2020 –September 2023\nSource: COVID -19–associated hospitalization data reported to CDC’s National Healthcare Safety Network (NHSN). \nhttps://covid.cdc.gov/covid -data -tracker/#trends_weeklyhospitaladmissions_select_00\n\n7Weekly provisional COVID -19 deaths  –National Vital Statistics System \n(NVSS), United States January 2020 –September 2023\nSource : Provisional Deaths from the CDC’s National Center for Health Statistics (NCHS) National Vital Statistics System (NVSS). htt ps://covid.cdc.gov/covid -data -tracker/#trends_weeklydeaths_weeklydeathrateaa_00 \nData during recent periods are incomplete because of the lag in time between when a death occurs and when a death certificate iscompleted, submitted to NCHS, and processed for reporting. This delay can range \nfrom 1 week to 8 weeks or more, depending on the jurisdiction. The most recent 3 weeks of mortality counts are shaded grey be cause NVSS reporting is <95% during this period.\n\nCOVID -19 Vaccine Policy\n▪ACIP met September 12, 2023 to review the available evidence for \nupdated COVID -19 vaccines (monovalent, XBB.1.5 component)\n▪ACIP recommended updated COVID -19 vaccines as authorized under EUA \nor approved by BLA in persons aged ≥6 months\n–Moderna COVID -19 vaccine in persons ≥6 months \n–Pfizer -BioNTech COVID -19 vaccine in persons ≥6 months \n–Novavax COVID -19 vaccine in persons ≥ 12 years\n▪All anticipated updated (2023 –2024 Formula) vaccines are now \nauthorized or approvedCOVID -19 Vaccine Policy\n9\n▪All doses should be homologous (i.e., from the same manufacturer) \n▪All Moderna doses in ages 6 months –11 years are now 25 µcg Recommendations for children aged 6 months –4 years without\nimmunocompromise\nDoses recommended:\n▪Initial series of 2 Moderna vaccine doses OR 3 Pfizer -\nBioNTech vaccine doses \n▪Including a t least 1 dose of 2023 –2024 COVID -19 vaccine \n10\nRecommended 2023 –2024 COVID -19 mRNA vaccines for people who are NOT \nimmunocompromised, aged 6 months –4 years*†\n*For information about administration intervals and children who transition from age 4 years to age 5 years, see Table 1 in t he Interim Clinical Considerations for \nUse of COVID -19 Vaccines\n† COVID -19 vaccination history refers to previous receipt of doses of Original monovalent mRNA or bivalent mRNA vaccine or a com bination of the two; for people \nages 12 years and older, Original monovalent Novavax COVID -19 Vaccine doses, alone or in combination with any mRNA vaccine doses ; and for people ages 18 \nyears and older, Janssen COVID -19 Vaccine doses, alone or in combination with any mRNA or Original monovalent Novavax vaccine do ses.\n11\n▪Exceptional situations: In the following exceptional situations , a different age -\nappropriate COVID -19 vaccine may be administered:\n–Same vaccine not available\n–Previous dose unknown\n–Person would otherwise not complete the vaccination series\n–Person starts but unable to complete a vaccination series with the same COVID -19 \nvaccine due to a contraindication\n▪AVaccine Adverse Event Reporting System (VAERS) report is not indicated for these \nexceptional situations.Prior Version of Interim Clinical Considerations on \nInterchangeability of COVID -19 vaccines\nClinical Guidance for COVID -19 Vaccination | CDC12\n▪COVID -19 vaccine doses from the same manufacturer should be administered \nwhenever recommended. In the following circumstances , an age -appropriate COVID -19 \nvaccine from a different manufacturer may be administered:\n–Same vaccine not available at the vaccination site at the time of the clinic visit \n–Previous dose unknown\n–Person would otherwise not receive a recommended vaccine dose\n–Person starts but unable to complete a vaccination series with the same COVID -19 \nvaccine due to a contraindication\n▪A Vaccine Adverse Event Reporting System (VAERS) report is not indicated in these \ncircumstances.Updated Version of Interim Clinical Considerations on \nInterchangeability of COVID -19 vaccines\n13\n▪Updated guidance for children who transition during the initial COVID -19 vaccination \nseries from age 4 years to age 5 years and children who are moderately or severely \nimmunocompromised and transition from age 11 years to age 12 years to receive the \nage-appropriate dosage based on their age on the day of vaccinationAdditional Updates to Interim Clinical Considerations\nClinical Guidance for COVID -19 Vaccination | CDC14\nRecommendations for people aged 5 years and older without\nimmunocompromise \nDoses recommended:\n•1 dose of 2023 –2024 COVID -19 vaccine\n▪mRNA COVID -19 vaccines authorized or approved for ages ≥6 months and Novavax COVID -19 vaccine \nauthorized for ages ≥12 years \n▪Unvaccinated persons receiving Novavax COVID -19 should complete a 2 -dose initial series\n▪New harmonized age cutoff for recommendations for young children for Moderna and Pfizer -\nBioNTech COVID -19 vaccines resulting in simplified recommendations for 5 -year -olds\n▪All Moderna doses in ages 6 months –11 years are now 25 µcg \n▪2023 –2024 COVID -19 vaccine dose is recommended at least 2 months after receipt of the last \nCOVID -19 vaccine dose\n15\nRecommended 2023 –2024 COVID -19 mRNA vaccines for people who are NOT \nimmunocompromised, aged 5 –11 years*†\n*For information about administration intervals and children who transition from age 4 years to age 5 years, see Table 1 in t he Interim Clinical Considerations for \nUse of COVID -19 Vaccines\n† COVID -19 vaccination history refers to previous receipt of doses of Original monovalent mRNA or bivalent mRNA vaccine or a com bination of the two; for people \nages 12 years and older, Original monovalent Novavax COVID -19 Vaccine doses, alone or in combination with any mRNA vaccine doses ; and for people ages 18 \nyears and older, Janssen COVID -19 Vaccine doses, alone or in combination with any mRNA or Original monovalent Novavax vaccine do ses.16\nRecommended COVID -19 vaccination schedule for people who are NOT moderately or \nseverely immunocompromised , aged ≥12 years*†\n*For information about administration intervals and children who transition from age 4 years to age 5 years, see Table 1 in t he Interim Clinical Considerations for \nUse of COVID -19 Vaccines\n† COVID -19 vaccination history refers to previous receipt of doses of Original monovalent mRNA or bivalent mRNA vaccine or a com bination of the two; for people \nages 12 years and older, Original monovalent Novavax COVID -19 Vaccine doses, alone or in combination with any mRNA vaccine doses ; and for people ages 18 \nyears and older, Janssen COVID -19 Vaccine doses, alone or in combination with any mRNA or Original monovalent Novavax vaccine do ses. 17\nRecommendations for people aged ≥6 months who are \nmoderately or severely immunocompromised\nDoses recommended:\n▪Initial COVID -19 vaccine series*\n▪At least 1 2023 –2024 COVID -19 vaccine dose\n▪May receive 1 or more additional 2023 -2024 \nCOVID -19 vaccine doses**\n*Series of 3 homologous mRNA COVID -19 vaccine doses or 2 homologous Novavax COVID -19 vaccine doses \nat time of initial vaccination. This could also include a history of receipt of 1 or more doses of Novavax or \nJanssen, including in combination with mRNA vaccine dose(s). \n**Further additional dose(s) may be administered, informed by the clinical judgement of a healthcare \nprovider and personal preference and circumstances. Further additional doses should be administered at \nleast 2 months after the last 2023 -2024 COVID -19 vaccine dose. \n18\nRecommended 2023 –2024 COVID -19 vaccines for people who ARE moderately or severely \nimmunocompromised, aged 6 months –4 years*†\n* For information about administration intervals and children who transition from age 4 years to age 5 years or age 11 years to age 12 years during an mRNA \nvaccination series, and administration of additional dose(s), see Table 2 in the Interim Clinical Considerations for Use of COVID -19 Vaccines\n† COVID -19 vaccination history refers to previous receipt of doses of Original monovalent mRNA or bivalent mRNA vaccine or a com bination of the two; for \npeople ages 12 years and older, Original monovalent Novavax COVID -19 Vaccine doses, alone or in combination with any mRNA vaccin e doses; and for people \nages 18 years and older, Janssen COVID -19 Vaccine doses, alone or in combination with any mRNA or Original monovalent Novavax va ccine doses. 19\nRecommended 2023 –2024 COVID -19 vaccines for people who ARE moderately or severely \nimmunocompromised, aged 5 –11 years*†\n* For information about administration intervals and children who transition from age 4 years to age 5 years or age 11 years to age 12 years during an mRNA \nvaccination series, and administration of additional dose(s), see Table 2 in the Interim Clinical Considerations for Use of COVID -19 Vaccines\n† COVID -19 vaccination history refers to previous receipt of doses of Original monovalent mRNA or bivalent mRNA vaccine or a com bination of the two; for \npeople ages 12 years and older, Original monovalent Novavax COVID -19 Vaccine doses, alone or in combination with any mRNA vaccin e doses; and for people \nages 18 years and older, Janssen COVID -19 Vaccine doses, alone or in combination with any mRNA or Original monovalent Novavax va ccine doses.\n 20\nRecommended COVID -19 vaccination schedule for people who ARE moderately or \nseverely immunocompromised , aged ≥12 years*†\n* For information about administration intervals and children who transition from age 4 years to age 5 years or age 11 years to age 12 years during an mRNA \nvaccination series, and administration of additional dose(s), see Table 2 in the Interim Clinical Considerations for Use of COVID -19 Vaccines\n† COVID -19 vaccination history refers to previous receipt of doses of Original monovalent mRNA or bivalent mRNA vaccine or a com bination of the two; for \npeople ages 12 years and older, Original monovalent Novavax COVID -19 Vaccine doses, alone or in combination with any mRNA vaccin e doses; and for people \nages 18 years and older, Janssen COVID -19 Vaccine doses, alone or in combination with any mRNA or Original monovalent Novavax va ccine doses. 21\n▪Consideration of additional COVID -19 vaccine doses in older adults\n–Anticipated for February 2024 ACIP meeting\n–Policy discussion will occur prior to individuals reaching 6 months since their last dose\n▪Preparations for future COVID -19 vaccine formula updates\n–Discussions will begin atJune 2024 ACIP meeting \n▪Continue to monitor vaccine effectiveness, vaccine safety, and COVID -19 epidemiology\n–COVID -19 vaccine recommendations can be updated if neededUpcoming COVID -19 policy discussions\n22\nAcknowledgements\n23▪Monica Godfrey\n▪Danielle Moulia\n▪Katherine Fleming -Dutra\n▪Ruth Link -Gelles\n▪Sarah Meyer\n▪Elisha Hall\n▪Susan Goldstein\n▪Mary Chamberland\n▪JoEllen Wolicki\n▪Natalie Thornburg\n▪Sierra Scarbrough\n▪Aron Hall\n▪Christopher Taylor\n▪Fiona Havers ▪Dave Wentworth\n▪Meredith McMorrow\n▪COVID -NET Team\n▪Coronavirus and other Respiratory Viruses Division\n▪National Center for Immunization and Respiratory \nDiseases\nFor more information, contact CDC\n1-800 -CDC -INFO (232 -4636)\nTTY:  1 -888 -232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention.\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.", "summary": "Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. COVID -19 Vaccine Policy and Next Steps October 26, 2023 Megan Wallace, DrPH, MPH COVID -19 Epidemiology 3Trends in weighted variant proportion estimates and Nowcast –…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-25-26-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-10-25-26/03-COVID-Wallace-508.pdf", "doc_date": "2023-10-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 24}
{"title": "01 Pneumo Kobayashi 508", "content": "Centers for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nPneumococcal Vaccines Work Group\nOctober 2023, ACIP meeting\nOctober 26, 2023\nMiwako Kobayashi, MD, MPH\n•The Pneumococcal Vaccines Work Group:\n•Reviews current data on pneumococcal disease burden, and on the efficacy, \neffectiveness, immunogenicity, and cost -effectiveness of pneumococcal vaccines \nand assesses the strength of the evidence;\n•Reviews current pneumococcal vaccine recommendations considering up -to-date \nevidence; and\n•Develops revised or updated policy options for pneumococcal vaccines as needed.Work Group Purpose\nAdvisory Committee on Immunization Practices (ACIP) Work Groups | CDC\nACIP Members\n▪Katherine Poehling (Chair)\n▪Sarah Long \nEx Officio Members\n▪Jeffrey Kelman (CMS)\n▪Lucia Lee            (FDA)\n▪Tina Mongeau (FDA)\n▪Uzo Chukwuma (IHS)\n▪Mamodikoe Makhene (NIH)\nLiaison Representatives\n▪Lynn Fisher                (AAFP)\n▪Mark Sawyer             (AAP/COID)\n▪Jason Goldman         (ACP)▪David Nace                 (AGS/AMDA)\n▪Cora Hoover               (AIM)\n▪Risa Claytor                 (HRSA)\n▪James McAuley         (IDSA)\n▪Aleksandra Wierzbowski   (NACI)\n▪Robert Hopkins    (NFID)\n▪Virginia Caine            (NMA)\nConsultants\n▪Monica Farley           (VAMC/Emory)\n▪Keith Klugman          (BMGF)\n▪Arthur Reingold        (UC Berkley)\n▪Lorry Rubin                 (CCMC)\n▪Richard Zimmerman (U. of Pittsburgh)Pneumococcal Vaccines Work Group\nDivision of Bacterial Diseases\n▪Diepreye Ayabina \n▪Adam Cohen\n▪Ryan Gierke             \n▪Jennifer Farrar     \n▪Noele Nelson\nImmunization Safety Office\n▪Pedro Moro               \nImmunization Services Division\n▪Janelle King\n▪Andrew Leidner\n▪Liz VelazquezArctic Investigations Program\n▪Marc Fischer\nCDC Lead\n▪Miwako Kobayashi\nGRADE/ EtR consultants\n▪Doug Campos -Outcalt\n▪Rebecca MorganCDC Contributors and Consultants\nHistory of ACIP Pneumococcal Vaccine Recommendations \nthrough 2019\n1984PPSV23 :Adults aged \n≥65 years and \nindividuals with \nunderlying conditions\n2000 2010 2019 2014 2012\nPCV7 :Children PCV13 :Children \n(replaced PCV7)PCV13 :Adults with \nimmunocompromising \nconditions in addition \nto PPSV23PCV13 :All adults aged \n≥65 years in addition \nto PPSV23PCV13 :based on SCDM \nfor adults aged ≥65 \nyears; routine PPSV23\nrecommendation\nSCDM: shared clinical decision -making\nRecent ACIP Pneumococcal Vaccine Recommendations, \n2021 –2023\n2021 2023 2022\nPCV15 :ChildrenPCV20 :Expanded \nindication for adults \nwho previously \nreceived PCV13\nPCV20 :ChildrenPCV15 and PCV20 :\nAdults who have not \nreceived PCV or whose \nvaccination history is \nunknown\nMultiple updates have been made to adult \npneumococcal vaccine recommendations since 2012.\n▪Prior to the COVID -19 pandemic, estimated to have caused \nevery year1:\n–≥100,000 non -invasive pneumococcal pneumonia hospitalizations\n–≥30,000 invasive pneumococcal disease (IPD) cases (e.g., bacteremic pneumonia, \npneumococcal bacteremia, meningitis)\n•3,000 IPD deaths\n▪Preliminary data show increase in IPD cases in late 20222\n–Increase in other invasive bacterial infections reported in children3,4Pneumococcal Disease Burden among U.S. Adults\n1. Kobayashi M. October 20, 2021 ACIP Meeting Presentation. Considerations for Age -Based and Risk -Based Use of PCV15 and PCV20 amon g U.S. Adults and Proposed Policy \nOptions. \n2. CDC Active Bacterial Core surveillance unpublished data\n3. Notes from the Field: Update on Pediatric Intracranial Infections —19 States and the District of Columbia, January 2016 –March 2 023 | MMWR (cdc.gov)\n4. Notes from the Field: Increase in Pediatric Invasive Group A Streptococcus Infections —Colorado and Minnesota, October –December 2022 | MMWR (cdc.gov)\nInvasive pneumococcal disease incidence among adults aged ≥65 years \nreached a historically low level early in the COVID -19 pandemic\nIPD=invasive pneumococcal disease\nCDC Active Bacterial Core surveillancePCV13: children\nPCV13: adults\nApproximately 40% of IPD cases in adults aged ≥65 years were caused \nby serotypes not contained in currently recommended vaccines\nCDC Active Bacterial Core surveillance\nNew Adult Pneumococcal Vaccines in Advanced Stages of Development\n1 3 4 5 6\nA6\nB7 \nF9\nV1\n41\n8\nC1\n9\nA1\n9\nF2\n3\nF2\n2\nF3\n3\nF8 1\n0\nA1\n1\nA1\n2\nF1\n5\nB2 9\nN1\n7\nF2\n01\n5\nA1\n5\nC1\n6\nF2\n3\nA2\n3\nB2\n4\nF3\n13\n5\nB\nPCV15\nPCV20\nPPSV23\nPn-\nMAPS24v20\nB\nVAX -2420\nB\nV11620\nA\n24-valent pneumococcal vaccines \n•Completed phase 1/2 study for adults1Pn-MAPS24v, GSK\n•Completed phase 1/2 studies for adults, undergoing phase 2 studies \nin infants2VAX -24, Vaxcyte\n21-valent pneumococcal conjugate vaccine V116, Merck\n•Completed phase 1/2 study for adults3\n•Phase 3 studies in adults are currently ongoing\n1. Chichili et al. Vaccine 2022; 2. ClinicalTrials.gov ID: NCT05266456, NCT05297578, and NCT05844423 ; 3. Platt et al. Lancet ID 2022. \n▪Review evidence on use of 21-valent pneumococcal conjugate \nvaccine (V116) for adults\n–Biologics License Application for V116 to the FDA is anticipated in Q4 of 2023, with \nan anticipated FDA approval in the first half of 2024Next Steps for Pneumococcal Vaccines Work Group\n▪Evidence to support EtR domains including,\n–Epidemiology of pneumococcal disease among U.S. adults\n–Assessment of pneumococcal disease caused by serotypes not included in V116 (but \nincluded in existing vaccines)\n–Phase 2/3 clinical trial data on V116 among adults\n–Feasibility and resource use involved in V116 use among adults\n–Health equity considerations\n▪Aim to have an ACIP vote on policy options shortly after FDA \napproval of V116Data to be Reviewed by Work Group\nFor more information, contact CDC\n1-800 -CDC -INFO (232 -4636)\nTTY:  1 -888 -232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention.\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nThank you!", "summary": "Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. Pneumococcal Vaccines Work Group October 2023, ACIP meeting October 26, 2023 Miwako Kobayashi, MD, MPH •The Pneumococcal Vaccines Work Group: •Reviews current data on…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-25-26-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-10-25-26/01-Pneumo-Kobayashi-508.pdf", "doc_date": "2023-10-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 13}
{"title": "06 influenza olson 508", "content": "Centers for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nEffectiveness of Maternal Influenza Vaccination during Pregnancy \nagainst Influenza- associated Hospitalizations & ED Visits in Infants <6 \nMonths of Age\nSamantha M. Olson, MPH\nNVSN Flu Lead/ EpidemiologistInfluenza Prevention and Control Team (IPACT)\nInfluenza Division\nACIP Meeting: Influenza Session\nOctober 25, 2023\n•Influenza virus infection during pregnancy is associated with severe disease and may be associated \nwith some adverse birth outcomes . Background\n•Influenza vaccination during pregnancy can protect infants <6 months of age, who are not age -eligible \nfor vaccination. \n•Randomized control trials conducted outside of the US showed a maternal vaccine efficacy against \nlaboratory -confirmed influenza in infants of 30-63%\n•There is a lack of real -world, multi -center, multi -season, and US data on maternal vaccine effectiveness (VE) \nagainst medically -attended influenza in infants•Receipt of inactivated influenza vaccine during pregnancy is safe and effective.\n•Since the COVID -19 pandemic, influenza vaccination uptake during pregnancy is ~5-15% lower than pre -\npandemic seasons.\nCurrent ACIP Wording (As of 2021- 2022 Influenza Season):\n–Pregnant persons in the third trimester: Vaccination during July and August can be considered for \npregnant persons who are in the third trimester because vaccination might reduce risk for influenza \nillness in their infants during the first months after birth, when they are too young to receive \ninfluenza vaccine (33 –36). For pregnant persons in the first or second trimester during July and \nAugust, waiting to vaccinate until September or October is preferable , unless there is concern that \nlater vaccination might not be possible.Prevention and Control of Seasonal Influenza with Vaccines: \nRecommendations of the Advisory Committee on Immunization Practices\nhttps://www.cdc.gov/mmwr/volumes/71/rr/rr7101a1.htm\nhttps://www.cdc.gov/mmwr/volumes/70/rr/rr7005a1.htm?s_cid=rr7005a1_w\nInfluenza Division  |NCIRDQuestion:\nDoes maternal influenza vaccination during pregnancy\nreduce influenza -associated hospitalizations and \nemergency department (ED) visits in infants <6 months \nof age?\nNVSN* Pediatric Inpatient & ED Network Sites\nSeattle Children’s \nCincinnati \nChildren’sChildren’s Hospital of \nPittsburgh\nVanderbilt University \nNashville\nTexas Children’s Hospital \nHouston\nChildren’s Mercy Hospital \nKansas City\nUniversity of Rochester \n*NVSN --New Vaccine Surveillance Network\n•Enrollment: Infants <6 months of age admitted to the hospital or emergency department during 4 influenza seasons \n(from Fall 2016 through Spring 2020) at 7 pediatric medical centers within the NVSN\n•Cases: \n•Tested positive for influenza by RT -PCR with acute respiratory illness (ARI) symptoms within 10 days of symptom \nonset \n•Controls: Tested negative for influenza with ARI symptoms\n•Design: Test-negative design\n•Odds of maternal influenza vaccination ≥14 days prior to delivery in case infants with influenza were compared \nto control infants with non -influenza respiratory illness\n•Vaccination status: Vaccination was defined as influenza vaccine received during pregnancy\n•Documented (registry or providers) or self -reported vaccination with timing (date or trimester) during pregnancy\n•Data on maternal influenza infection during pregnancy was not collected\n•Analysis: VE= (1 – adjusted odds ratio) x 100%\n•Adjusted for infant age, NVSN site, and calendar timeMethods\nFigure. Timing of maternal influenza vaccination during pregnancy in the context of infant age and \ninfluenza seasonality\n\nFigure. Timing of maternal influenza vaccination during pregnancy in the context of infant age and \ninfluenza seasonality\n\nFigure. Timing of maternal influenza vaccination during pregnancy in the context of infant age and \ninfluenza seasonality\n\nFigure. Timing of maternal influenza vaccination during pregnancy in the context of infant age and \ninfluenza seasonality\n\nFigure. Timing of maternal influenza vaccination during pregnancy in the context of infant age and \ninfluenza seasonality\n\nFigure. Timing of maternal influenza vaccination during pregnancy in the context of infant age and \ninfluenza seasonality\n\nInfluenza Division  |NCIRDResults\n4,049 infants <6 months of age enrolled \nbetween the 2016- 2017 through the \n2019- 2020 flu seasons from 7 pediatric \nmedical institutions\n3,764 infants included\n2,007 (53%) born to vaccinated mothers\n1,757 (47%) born to unvaccinated \nmothers285 Were excluded (21 cases, 264 controls)\n92Born to mothers vaccinated <14 days \nprior to delivery (8 cases, 84 controls)\n193 Had unknown vaccination timing (13 \ncases, 180 controls)\n223 case -infants tested positive for influenza\n94 (42%) born to vaccinated mothers\n129 (58%) born to unvaccinated mothers3,541 control -infants tested negative for influenza \n1,913 (54%) born to vaccinated mothers\n1,642 (46%) born to unvaccinated mothers\nCharacteristicCase status Maternal Vaccination Status\nCase -infants \n(N=223)Control -infants \n(N=3541)Vaccinated \n(N=2007)Unvaccinated (N=1757)\nMedian age (IQR) –months 3 (2, 5) 2 (1, 4) 2 (1, 4) 3 (2, 4)\nAge group –no. (%)\n0-2 months 106 (48) 2147 (61) 1342 (67) 911 (52)\n3-5 months 117 (52) 1394 (39) 665 (33) 846 (48)\nFemale sex –no. (%) 102 (46) 1533 (43) 864 (43) 771 (44)\nRace and ethnic group –no./ total no. (%)\nWhite, non -Hispanic69/223 (31) 1517/3540 (43) 920/2006 (46) 666/1757 (38)\nBlack, non -Hispanic69/223 (31) 695/3540 (20) 302/2006 (15) 462/1757 (26)\nHispanic64/223 (29) 1008/3540 (28) 585/2006 (29) 487/1757 (28)\nOther21/223 (9) 320/3540 (9) 199/2006 (10) 142/1757 (8)\nAt least one underlying condition in \ninfants –no./total no. (%)18 (8) 372 (11) 184 (9) 206 (12)Breastfeeding at Enrollment 94/223 (42) 1616/3536 (46) 1051/2005 (52) 659/1754 (38)\nCharacteristicCase status Maternal Vaccination Status\nCase -infants \n(N=223)Control -infants \n(N=3541)Vaccinated \n(N=2007)Unvaccinated (N=1757)\nMedian age (IQR) –months 3 (2, 5) 2 (1, 4) 2 (1, 4) 3 (2, 4)\nAge group –no. (%)\n0-2 months 106 (48) 2147 (61) 1342 (67) 911 (52)\n3-5 months 117 (52) 1394 (39) 665 (33) 846 (48)\nFemale sex –no. (%) 102 (46) 1533 (43) 864 (43) 771 (44)\nRace and ethnic group –no./ total no. (%)\nWhite, non -Hispanic69/223 (31) 1517/3540 (43) 920/2006 (46) 666/1757 (38)\nBlack, non -Hispanic69/223 (31) 695/3540 (20) 302/2006 (15) 462/1757 (26)\nHispanic64/223 (29) 1008/3540 (28) 585/2006 (29) 487/1757 (28)\nOther21/223 (9) 320/3540 (9) 199/2006 (10) 142/1757 (8)\nAt least one underlying condition in \ninfants –no./total no. (%)18 (8) 372 (11) 184 (9) 206 (12)Breastfeeding at Enrollment 94/223 (42) 1616/3536 (46) 1051/2005 (52) 659/1754 (38)Case -infants and those born to unvaccinated mothers were older than control -\ninfants and those born to vaccinated mothers.\nCharacteristicCase status Maternal Vaccination Status\nCase -infants \n(N=223)Control -infants \n(N=3541)Vaccinated \n(N=2007)Unvaccinated (N=1757)\nMedian age (IQR) –months 3 (2, 5) 2 (1, 4) 2 (1, 4) 3 (2, 4)\nAge group –no. (%)\n0-2 months 106 (48) 2147 (61) 1342 (67) 911 (52)\n3-5 months 117 (52) 1394 (39) 665 (33) 846 (48)\nFemale sex –no. (%) 102 (46) 1533 (43) 864 (43) 771 (44)\nRace and ethnic group –no./ total no. (%)\nWhite, non -Hispanic69/223 (31) 1517/3540 (43) 920/2006 (46) 666/1757 (38)\nBlack, non -Hispanic69/223 (31) 695/3540 (20) 302/2006 (15) 462/1757 (26)\nHispanic64/223 (29) 1008/3540 (28) 585/2006 (29) 487/1757 (28)\nOther21/223 (9) 320/3540 (9) 199/2006 (10) 142/1757 (8)\nAt least one underlying condition in \ninfants –no./total no. (%)18 (8) 372 (11) 184 (9) 206 (12)Breastfeeding at Enrollment 94/223 (42) 1616/3536 (46) 1051/2005 (52) 659/1754 (38)Infant case status and maternal vaccination status differed by race and ethnic \ngroup .\nCharacteristicCase status Maternal Vaccination Status\nCase -infants \n(N=223)Control -infants \n(N=3541)Vaccinated \n(N=2007)Unvaccinated (N=1757)\nMedian age (IQR) –months 3 (2, 5) 2 (1, 4) 2 (1, 4) 3 (2, 4)\nAge group –no. (%)\n0-2 months 106 (48) 2147 (61) 1342 (67) 911 (52)\n3-5 months 117 (52) 1394 (39) 665 (33) 846 (48)\nFemale sex –no. (%) 102 (46) 1533 (43) 864 (43) 771 (44)\nRace and ethnic group –no./ total no. (%)\nWhite, non -Hispanic69/223 (31) 1517/3540 (43) 920/2006 (46) 666/1757 (38)\nBlack, non -Hispanic69/223 (31) 695/3540 (20) 302/2006 (15) 462/1757 (26)\nHispanic64/223 (29) 1008/3540 (28) 585/2006 (29) 487/1757 (28)\nOther21/223 (9) 320/3540 (9) 199/2006 (10) 142/1757 (8)\nAt least one underlying condition in \ninfants –no./total no. (%)18 (8) 372 (11) 184 (9) 206 (12)Breastfeeding at Enrollment 94/223 (42) 1616/3536 (46) 1051/2005 (52) 659/1754 (38)More infants born to vaccinated mothers were breastfeeding on enrollment, \nand more infants born to unvaccinated mothers had underlying conditions . \nCharacteristicCase status Maternal Vaccination Status\nCase -infants \n(N=223)Control -infants \n(N=3541)Vaccinated \n(N=2007)Unvaccinated (N=1757)\nPreterm birth (born <37 weeks gestation) \n–no./ total no. (%)37/223 (17) 613/3535 (17) 315/2004 (16) 335/1754 (19)\n35-<37 weeks 20/36 (56) 319/600 (53) 167/307 (54) 172/329 (52)\n30-34 weeks 14/36 (39) 219/600 (37) 122/307 (40) 111/329 (34)\n≤29 weeks 2/36 (6) 62/600 (10) 18/307 (6) 46/329 (14)\nNVSN sites– no. (%)\nNashville 38 (17) 708 (20) 361 (18) 385 (22)\nRochester 14 (6) 358 (10) 213 (11) 159 (9)\nCincinnati 42 (19) 345 (10) 198 (10) 189 (11)\nSeattle 26 (12) 359 (10) 281 (14) 104 (6)\nHouston 39 (17) 797 (23) 391 (19) 445 (25)\nKansas City 35 (16) 317 (9) 174 (9) 178 (10)\nPittsburgh 29 (13) 657 (19) 389 (19) 297 (17)\nSeason of enrollment – no. (%)\n2016- 2017 49 (22) 778 (22) 462 (23) 365 (21)\n2017- 2018 60 (27) 829 (23) 429 (21) 460 (26)\n2018- 2019 45 (20) 986 (28) 560 (28) 471 (27)\n2019- 2020 69 (31) 948 (27) 556 (28) 461 (26)\nCharacteristicCase status Maternal Vaccination Status\nCase -infants \n(N=223)Control -infants \n(N=3541)Vaccinated \n(N=2007)Unvaccinated (N=1757)\nPreterm birth (born <37 weeks gestation) \n–no./ total no. (%)37/223 (17) 613/3535 (17) 315/2004 (16) 335/1754 (19)\n35-<37 weeks 20/36 (56) 319/600 (53) 167/307 (54) 172/329 (52)\n30-34 weeks 14/36 (39) 219/600 (37) 122/307 (40) 111/329 (34)\n≤29 weeks 2/36 (6) 62/600 (10) 18/307 (6) 46/329 (14)\nNVSN sites– no. (%)\nNashville 38 (17) 708 (20) 361 (18) 385 (22)\nRochester 14 (6) 358 (10) 213 (11) 159 (9)\nCincinnati 42 (19) 345 (10) 198 (10) 189 (11)\nSeattle 26 (12) 359 (10) 281 (14) 104 (6)\nHouston 39 (17) 797 (23) 391 (19) 445 (25)\nKansas City 35 (16) 317 (9) 174 (9) 178 (10)\nPittsburgh 29 (13) 657 (19) 389 (19) 297 (17)\nSeason of enrollment – no. (%)\n2016- 2017 49 (22) 778 (22) 462 (23) 365 (21)\n2017- 2018 60 (27) 829 (23) 429 (21) 460 (26)\n2018- 2019 45 (20) 986 (28) 560 (28) 471 (27)\n2019- 2020 69 (31) 948 (27) 556 (28) 461 (26)More infants born to unvaccinated mothers were born preterm.\nPreterm birth (born <37 weeks \ngestation) –no./ total no. (%)35/216 (16) 612/3597 (17) 310/2051 (15) 337/1762 (19)\n35-<37 weeks 19/34 (56) 318/602 (53) 166/305 (54) 171/331 (52)\n30-34 weeks 14/34 (41) 219/602 (36) 120/305 (39) 113/331 (34)\n≤29 weeks 1/34 (3) 65/602 (11) 19/305 (6) 47/331 (14)CharacteristicCase status Maternal Vaccination Status\nCase -infants \n(N=223)Control -infants \n(N=3541)Vaccinated \n(N=2007)Unvaccinated (N=1757)\nPreterm birth (born <37 weeks gestation) \n–no./ total no. (%)37/223 (17) 613/3535 (17) 315/2004 (16) 335/1754 (19)\n35-<37 weeks 20/36 (56) 319/600 (53) 167/307 (54) 172/329 (52)\n30-34 weeks 14/36 (39) 219/600 (37) 122/307 (40) 111/329 (34)\n≤29 weeks 2/36 (6) 62/600 (10) 18/307 (6) 46/329 (14)\nNVSN sites– no. (%)\nNashville 38 (17) 708 (20) 361 (18) 385 (22)\nRochester 14 (6) 358 (10) 213 (11) 159 (9)\nCincinnati 42 (19) 345 (10) 198 (10) 189 (11)\nSeattle 26 (12) 359 (10) 281 (14) 104 (6)\nHouston 39 (17) 797 (23) 391 (19) 445 (25)\nKansas City 35 (16) 317 (9) 174 (9) 178 (10)\nPittsburgh 29 (13) 657 (19) 389 (19) 297 (17)\nSeason of enrollment – no. (%)\n2016- 2017 49 (22) 778 (22) 462 (23) 365 (21)\n2017- 2018 60 (27) 829 (23) 429 (21) 460 (26)\n2018- 2019 45 (20) 986 (28) 560 (28) 471 (27)\n2019- 2020 69 (31) 948 (27) 556 (28) 461 (26)Vaccination status differed by NVSN site and flu season of enrollment.\nMaternal Vaccine Effectiveness against Influenza -associated \nHospitalizations and Emergency Department Visits in Infants <6 months \nOverall maternal vaccine effectiveness against influenza hospitalizations \nand emergency department visits in infants <6 months of age is 34%\nMaternal vaccine effectiveness was higher among infants <3 months,\nvaccinated during the third trimester , and against hospital admission\nMaternal vaccine effectiveness was consistent with other VE estimates by\ninfluenza type and subtype for the 2016 -17 through 2019 -20 flu seasons.\n\nMaternal Vaccine Uptake \nInfluenza vaccine uptake during \npregnancy is nationally consistent \nbut suboptimal.\nBenefits to Infants\nMaternal vaccination was \nassociated with reduced odds of \ninfluenza hospitalizations & ED \nvisits in infants <6 months of age. \nHighest Vaccine Effectiveness\nVE was greatest among infants <3 \nmonths of age , those born to \nmothers vaccinated during their \nthird trimester of pregnancy, and \nagainst influenza -associated \nhospitalizations . \nSummary Policy Implications\nCurrently, there are no anticipated \nchanges to vaccination timing \nrecommendations during \npregnancy.\nInfluenza Division  |NCIRD\nAcknowledgments\nLeila C. Sahni\nNatasha B. Halasa \nLaura S. Stewart\nMarian G. Michaels\nJohn V. Williams\nJanet A. Englund\nEileen J. Klein\nMary A. Staat\nElizabeth P . Schlaudecker\nJennifer E. SchusterRangaraj Selvarangan\nGeoffrey A. Weinberg\nPeter G. Szilagyi\nManish M. Patel\nJulie A. Boom\nFlor M. Muñoz\nNVSN Research Teams & Study Participants", "summary": "Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. Effectiveness of Maternal Influenza Vaccination during Pregnancy  against Influenza- associated Hospitalizations & ED Visits in Infants <6  Months of Age Samantha M.…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-25-26-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-10-25-26/06-influenza-olson-508.pdf", "doc_date": "2023-10-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 27}
{"title": "07 influenza kondor 508", "content": "1\nWHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza,  \nInfluenza Division, National Center for Immunization and Respiratory Diseases\nUpdate on Influenza B/Yamagata \nSurveillance\nRebecca Kondor, PhD\nInterim Director, WHO Collaborating Center for Surveillance, \nEpidemiology and Control of Influenza\nLead, Genomics Analysis Team\nVirology, Surveillance and Diagnosis Branch –Influenza Division –NCIRD\n2\nWHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza,  \nInfluenza Division, National Center for Immunization and Respiratory Diseases\nWHO’s Global Influenza Surveillance and Response System (GISRS)\nThe mission of GISRS is to protect people from \nthe threat of influenza by continuously functioning as a:\n•Global mechanism of surveillance, \npreparedness and response for seasonal, pandemic and zoonotic influenza\n•Global platform for monitoring influenza \nepidemiology and disease\n•Global alert for novel influenza viruses and \nother respiratory pathogens\nWHO GISRS\n3\nWHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza,  \nInfluenza Division, National Center for Immunization and Respiratory Diseases\n•GISRS National Influenza Centers (NICs) \n•Collect respiratory specimens from \nestablished networks of physicians, health \ncare centers or other sentinel sites, \nand/or they solicit influenza virus -positive \nsamples \n•Perform initial influenza virus detection, typing and subtyping\n•CDC develops and manufactures assays which are distributed by IRR\n•Share a subset of representative influenza virus specimens and/or isolates with \nWHO CCs for antigenic and genetic \ncharacterization and creation of candidate vaccine viruses\n•Report to WHO RespiMart\n•epidemiological information FluID\n•laboratory results to FluNet\n152 WHO National Influenza Centers in 129 Member States\n•7 WHO Collaborating Centers for Influenza \n•4 Essential Reference Laboratories \n•12 WHO H5 Reference LaboratoriesWHO’s Global Influenza Surveillance and Response System (GISRS)\nWHO GISRS\n4\nWHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza,  \nInfluenza Division, National Center for Immunization and Respiratory Diseases\nWHO GISRS\nUpdate on Influenza B/Yamagata Surveillance \nFluNet data can be delineated by surveillance site type\n•Sentinel –Sentinel surveillance systems collect high -quality data in a timely manner, systematically and routinely \nfrom sentinel surveillance sites representative of the population under surveillance. Case definition (ILI, SARI, ARI) \nand populations differ by country (e.g., only certain age groups, health -care workers, hospitalized)\n•Non -sentinel –Data reported in this category may include outbreak investigation, universal testing, testing at point \nof care or other systems apart from sentinel surveillance\n•Type not defined –These data may include sentinel or non -sentinel surveillance sources or both\nThe level of information reported to FluNet depends on the country and the laboratory where testing occurs\n•Rapid tests only determine influenza A or B\n•Large clinical and hospital laboratories often only determine influenza A or B, with some assays also determining influenza A subtype\n•A higher proportion of viruses from sentinel surveillance will include influenza A and B subtyping results\nWHO GISRS\n5\nWHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza,  \nInfluenza Division, National Center for Immunization and Respiratory Diseases\nTypes of Assays for B/lineage at NIC:\n•Serology Based\n•CDC WHO Kit \n•anti-B/Vic and anti -B/Yam goat antiserum –created by WHO CC Atlanta available in CDC IRR\n•52 countries recently ordered kits\n•HI Assay –anti-B/Vic and anti -B/Yam ferret antiserum provided by WHO CCs\n•Molecular Based\n•CDC RT- PCR B Lineage Assay RUO -created by WHO CC Atlanta available in CDC IRR\n•104 countries recently ordered kits\n•Other RT -PCR assays\n•Sequencing (sanger or NGS) –clinical specimens or viral isolates\nGISRS NICs also submit specimens to WHO CCs for virus characterization\n•Using the above methods B lineage is attempted for all viruses received\n•WHO CC have confirmed ZERO circulating B/Yamagata lineage viruses collected after March 2020\n•Those reported as B/Yamagata were determined to be incorrectly lineage reports, negative for influenza \nor B/Yamagata component of LAIV\nNon-sentinel surveillance may use different assays than those listed above.WHO GISRSWHO GISRS\nUpdate on Influenza B/Yamagata Surveillance \n6\nWHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza,  \nInfluenza Division, National Center for Immunization and Respiratory Diseases\nWHO GISRS Influenza Surveillance \nSeptember 2017 -August 2020\nNorthern Hemisphere\nSouthern Hemisphere•Influenza B/Yamagata lineage viruses were the \npredominant B/lineage circulating during the 2017- 18 Northern Hemisphere and 2018 \nSouthern Hemisphere seasons\n•2018- 2019 Northern Hemisphere had much less \nB activity overall and B/Victoria lineage viruses predominated\n•2019 Southern Hemisphere showed regional differences in B/lineage circulation with B/Yamagata mainly circulating in South America\n•2019- 20 Northern Hemisphere season began \nwith an early B/Victoria lineage peak, followed by A(H1N1)pdm09\n•COVID -19 Pandemic and its mitigation saw a \ndrop in influenza virus detection and circulation\nGIP FLUNET PowerBI\n\n7\nWHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza,  \nInfluenza Division, National Center for Immunization and Respiratory Diseases\nWHO GISRS Influenza Surveillance \nSeptember 2020 -August 2023\nNorthern Hemisphere\nSouthern Hemisphere•GISRS NICs continued influenza surveillance \nduring the COVID -19 Pandemic\n•Influenza continued to be detected but without seasonal peaks in epidemics until late 2021\n•All influenza B activity due to B/Victoria lineage\n•February 1 – August 31, 2023\n•1/3 of all viruses detected by GISRS were influenza B\n•Parts of Northern Hemisphere saw second peak of activity due to B/Victoria and A(H1N1)pdm09 viruses\n•Southern Hemisphere 2023 season co -circulation \nof B/Victoria and A(H1N1)pdm09 viruses\nGIP FLUNET PowerBI\n\n8\nWHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza,  \nInfluenza Division, National Center for Immunization and Respiratory Diseases\nCountries reporting influenza B detections to FluNet February 1 -August 31, 2023\nAll Types of Surveillance\nGIP FLUNET PowerBI Map made from data available at\n9\nWHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza,  \nInfluenza Division, National Center for Immunization and Respiratory Diseases\nVirus Detections by B lineage reported to FluNet\nAll Types of Surveillance\nData source: GIP FLUNET PowerBI1 B/Yamagata reported (non -sentinel surveillance)\n1 February 2023 through 31 August 2023\n1 B/Yam non -sentinel surveillance\n10\nWHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza,  \nInfluenza Division, National Center for Immunization and Respiratory Diseases\nVirus Detections by subtype reported to FluNet\nSentinel Surveillance\nData source: GIP FLUNET PowerBINo B/Yamagata detected in GISRS sentinel surveillance\n1 February 2023 through 31 August 2023\n11\nWHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza,  \nInfluenza Division, National Center for Immunization and Respiratory Diseases\nWHO GISRS Influenza B/Lineage Reports\nFebruary 1 –August 31, 2023\nAs of 31 August 2023•99,453 influenza B viruses detected in 139 countries\n•15,878 influenza B viruses had results from B/lineage assays reported to FluNet from all surveillance \ntypes\n•15 initial reports to GISRS as B/Yamagata underwent confirmation by WHO CCs and WHO Global \nInfluenza Programme\n•13 were confirmed as B/Victoria Lineage or negative for influenza and their FluNet records were \nupdated accordingly\n•2 did not have specimens available for confirmation testing at a WHO CC (one was not reported to FluNet ). These specimens did not yield viral isolates or sequence data.\n•All influenza B viruses received by WHO CCs were B/Victoria lineage\n•Genomic surveillance of influenza B viruses found only genet segments derived from circulating B/Victoria lineage\n•This data supports that B/Yamagata viruses are extremely rare and not responsible for recent epidemics\n•The majority of B/Yamagata reports are due to an incorrect lineage determination\n12\nWHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza,  \nInfluenza Division, National Center for Immunization and Respiratory Diseases\nWHO vaccine recommendations for the \nSouthern Hemisphere 2024\nWHO recommendation and technical reports available on the WHO web site: https://www.who.int/teams/global -influenza -programme/vaccines/who -recommendations It is recommended that vaccines licensed for use in the 2024 southern hemisphere influenza season \ncontain the following:\nTrivalent: Egg-based Vaccines\n-an A/Victoria/4897/2022 (H1N1)pdm09- like virus antigen* ; \n-an A/Thailand/8/2022 (H3N2) -like virus antigen** ; and \n-a B/Austria/1359417/2021 (B/Victoria lineage) -like virus.\nTrivalent: Cell- or recombinant- based Vaccines           \n-an A/Wisconsin/67/2022 (H1N1)pdm09- like virus antigen*; \n-an A/Massachusetts/18/2022 (H3N2) -like virus antigen**; and\n-a B/Austria/1359417/2021 (B/Victoria lineage) -like virus antigen.\nQuadrivalent: egg-or cell culture -or recombinant- based vaccines\n-Above 3 components; and a B/Phuket/3073/2013 (B/Yamagata lineage) -like antigen.\n* Different from that recommended for the 2023 southern hemisphere season but the same as the NH 2023 -24 recommendation.\n** Different from that recommended for the 2023 southern hemisphere season and from NH 2023 -24 recommendation.\n13\nWHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza,  \nInfluenza Division, National Center for Immunization and Respiratory Diseases\nWHO Vaccine Recommendations Summary\n•The absence of confirmed detection of naturally occurring B/Yamagata lineage viruses is \nindicative of very low risk of infection by B/Yamagata lineage viruses. \n•While influenza vaccines are safe and effective, the manufacture and use of inactivated and live attenuated vaccines containing B/Yamagata lineage viruses pose a theoretical risk of reintroduction of B/Yamagata lineage virus into the population. This risk can be mitigated by \nthe removal of B/Yamagata lineage viruses from the vaccines. \n•It was the opinion of the WHO influenza vaccine composition advisory committee that the \ninclusion of a B/Yamagata antigen as a component of influenza vaccines is no longer \nwarranted, and every effort should be made to exclude this component as soon as practically \npossible. \n•The committee recognizes that national or regional authorities are responsible for approving the composition and formulation of vaccines used in each country and should consider the \nuse & relative benefit(s) of trivalent or quadrivalent influenza vaccines.\n14\nWHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza,  \nInfluenza Division, National Center for Immunization and Respiratory Diseases\nOngoing Influenza B Surveillance \n•GISRS laboratories will continue to be supported by CDC for influenza testing, typing \nand influenza A/B subtyping through reagents available in IRR\n•GISRS laboratories and WHO CCs will continue to perform B/lineage testing\n•Any reports of B/Yamagata viruses will be confirmed by WHO CCs\n•For the 2023- 2024 season, US public health labs will continue to perform assays to \ndetermine B/lineage –all B/Yamagata detections will be sent to CDC for confirmation.\n•All US specimens with RT -PCR results of a mix of influenza A and B will also be sent to \nCDC for confirmation. The majority of previous results of A/B mixtures were from individual vaccinated with LAIV.\n15\nWHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza,  \nInfluenza Division, National Center for Immunization and Respiratory Diseases\nSupport and Disclaimer\nThe findings and conclusions in this report are those of the authors and do not necessarily represent \nthe official position of the Centers for Disease Control and Prevention.\nThese projects have been funded in part with federal funds from US Health and Human \nServices (National Institutes of Health, Centers for Disease Control, and the Biomedical \nAdvanced Research and Development Authority).", "summary": "1 WHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza,   Influenza Division, National Center for Immunization and Respiratory Diseases Update on Influenza B/Yamagata  Surveillance Rebecca Kondor, PhD Interim Director, WHO Collaborating Center for Surveillance,  Epidemiology and Control of Influenza Lead, Genomics Analysis Team Virology, Surveillance and Diagnosis Branch –Influenza Division –NCIRD 2 WHO Collaborating Center for Surveillance, Epidemiology and Control…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-october-25-26-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-10-25-26/07-influenza-kondor-508.pdf", "doc_date": "2023-10-25", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 15}
{"title": "01 RSV Mat Ped Long 508", "content": "1\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nMaternal/Pediatric Respiratory Syncytial Virus (RSV) \nWork Group\nSarah S. Long, MD\nChair, Maternal/Pediatric RSV Work Group\nACIP General Meeting\nSeptember 22, 2023\n2Each year in U.S. children aged less than 5 years, \nRSV is associated with…\n~1,500,0003\noutpatient visits~520,0003\nemergency department visits58,000 –80,0003,4\nhospitalizations100–3001,2\ndeaths\n1Thompson et al, JAMA, 2003 ; 2Hansen et al, JAMA Network Open, 2022 ; 3Hall et al, NEJM, 2009 ; 4McLaughlin et al, J Infect Dis, 2022 (*estimate 80,000 hospitalizations in infants \n<1y) \n3▪Most (68%) infants are infected in the first year of life and \nnearly all (97%) by age 2 years2\n▪2-3% of young infants will be hospitalized for RSV3,4,5\n▪RSV is a common cause of lower respiratory tract infection \nin infants \n▪Highest RSV hospitalization rates occur in first months of \nlife and risk declines with increasing age in early \nchildhood3,5\n▪79% of children hospitalized with RSV aged <2 years had no \nunderlying medical conditions3RSV is the leading cause of hospitalization in U.S. \ninfants1\n1Suh et al. JID 2022 ; 2Glezen et al, Arch Dis Child, 1986 ; 3Hall et al, Pediatrics, 2013 ; 4Langley & Anderson, PIDJ, 2011 ; 5CDC NVSN data\nImage: Goncalves et al. Critical Care \nResearch and Practice 2012\n4▪Epidemiology and burden of RSV in infants\n▪Virology and immunology of RSV\n▪Safety and efficacy of RSVpreF\n▪Cost effectiveness analysis for RSVpreF –CDC model\n▪Cost effectiveness analysis for RSVpreF –Comparison with manufacturer model\n▪Evidence to Recommendations framework for RSVpreF\n▪Clinical considerations for RSVpreFPrevious maternal/pediatric RSV ACIP presentations on \nRSVpreF vaccine\n5▪On August 21, 2023, FDA approved Pfizer RSVpreF vaccine for use in pregnant people for the \nprevention of RSV lower respiratory tract disease and severe lower respiratory tract disease in \ninfants from birth to 6 months of age\n▪Approved as a single dose to be given at 32 –36 weeks gestation\n–In phase 2b and 3 trials, vaccination was given during 24 –36 weeks gestation \n–A numerical imbalance in preterm births was observed in RSVpreF vaccine compared to \nplacebo recipients in two clinical studies\n–Available data are insufficient to establish or exclude a causal relationship between preterm \nbirth and RSVpreF\n–Additionally, a numerical imbalance in hypertensive disorders of pregnancy was observed in \nRSVpreF vaccine compared to placebo recipientsFDA approval for RSVpreF vaccine\nFDA Approves First Vaccine for Pregnant Individuals to Prevent RSV in Infants | FDA\nPackage Insert -ABRYSVO (STN 125768) (fda.gov)\nAugust 21, 2023 Approval Letter -ABRYSVO (STN 125768) (fda.gov)\n6▪Starting dosing at 32 weeks gestation can reduce the potential risk of and complications from \npreterm birth until additional safety data are available\n–Avoids the risk of extremely preterm births, where there is substantive morbidity and \nmortality, and very preterm births\n–Similar vaccine efficacy in 32 -36 weeks gestation compared to the overall study population\n▪FDA has required the manufacturer to conduct post -marketing studies to assess preterm birth \nand hypertensive disorders of pregnancy, including pre -eclampsiaFDA approval for RSVpreF vaccine (cont.)\nFDA Approves First Vaccine for Pregnant Individuals to Prevent RSV in Infants | FDA\nPackage Insert -ABRYSVO (STN 125768) (fda.gov)\nAugust 21, 2023 Approval Letter -ABRYSVO (STN 125768) (fda.gov)\n7▪On August 3, 2023, ACIP recommended nirsevimab for RSV prevention in infants\n–Infants aged <8 months born during or entering their first RSV season are \nrecommended to receive one dose of nirsevimab (50 mg for infants <5 kg and 100 \nmg for infants ≥5 kg)\n–Children aged 8 –19 months who are at increased risk of severe RSV disease and \nentering their second RSV season are recommended to receive one dose of \nnirsevimab (200 mg) RSVpreF vaccine is one of two available preventive \nproducts for RSV in infants\n8▪A person develops active immunity from infection or vaccination\n–Triggers an immune response\n–Immunologic memory provides prolonged protection that may be lifelong\n▪Passive immunity is transfer of preformed antibody produced externally to provide \nprotection to the recipient\n–From mother to baby through transplacental or breastmilk transfer\n–Direct administration of antibodies, such as IVIG or monoclonal antibodies\n–Provides temporary protection that wanes with timeBoth nirsevimab and maternal RSV vaccine provide passive \nimmunity\nIVIG= Intravenous Immunoglobulin Therapy\nhttps://www.cdc.gov/vaccines/vac -gen/immunity -types.htm\n9Agenda: Friday September 22, 2023\nRSVpreF Vaccine Safety Surveillance in Pregnancy from \nThe Vaccine Safety DatalinkDr. Malini DeSilva (HealthPartners \nInstitute)  \nMaternal RSV vaccine safety monitoring in the Vaccine \nAdverse Event Reporting System (VAERS) and V -safeDr. Pedro Moro (CDC/NCEZID)\nEconomic analysis of RSVpreF maternal vaccination Dr. David Hutton (University of \nMichigan)\nEconomics of Preventing Respiratory Syncytial Virus \nDisease among US Infants by Maternal Vaccination Prior \nto BirthDr. Ismael Ortega -Sanchez \n(CDC/NCIRD)\nEvidence to Recommendations Framework Updates: \nPfizer Maternal RSVpreF VaccineDr. Katherine Fleming -Dutra \n(CDC/NCIRD)\n10Agenda: Friday September 22, 2023 (cont.)\nUpdated clinical considerations for use of both \nnirsevimab and Pfizer RSVpreF vaccineDr. Jefferson Jones (CDC/NCIRD)\nImplementation considerations for maternal RSV \nvaccineDr. Georgina Peacock (CDC/NCIRD)\nVaccines for Childrens Resolution Dr. Jeanne Santoli (CDC/NCIRD)\nBreak\nPublic Comment\nBreak\nVote on recommendation and Vaccines for Children\nAdult and Pediatric Immunization Schedule Addendum Dr. Sarah Schillie (CDC/NCIRD)\n11▪Should Pfizer RSVpreF vaccine be recommended for pregnant people to be given \nduring 32 through 36 weeks gestation to prevent RSV lower respiratory tract infection \nin infants?Policy Question\n12Work group members (External)\nACIP Members\nSarah Long (chair)\nPablo Sanchez\nOliver Brooks\nCamille KottonConsultants\nCody Meissner (Dartmouth Geisel School of Medicine)\nHelen Chu (University of Washington)\nNatasha Halasa (Vanderbilt University)\nDenise Jamieson (Emory University School of Medicine)\nDaniel Feikin (World Health Organization)\nCarol Baker (University of Texas Health Science Center)\nKevin Ault (Western Michigan University)Liaisons\nJames McAuley (IDSA)\nPatsy Stinchfield (NFID)\nBrenna L. Hughes (ACOG)\nNicole Chaisson (AAFP)\nSean O’Leary (AAP)\nJennifer Schuster (PIDS)\nMolly Howell (AIM)GRADE/ EtR Consultants\nDoug Campos -Outcalt\nRebecca MorganEx Officio Members\nRachel Zhang (FDA -CBER)\nNicholas Geagan (FDA -CBER)\nJudy Beeler (FDA -CBER)\nYodit Belew (FDA -CDER)\nPrabha Viswanathan (FDA -CDER)\nSonnie Kim (NIH -NIAID)\nApril Killikelly (Public Health Agency of Canada)\nWinnie Siu (Public Health Agency of Canada)\nValerie Marshall (OIDP/OASH)\nJessica Lee (CMS/CMCS)\nTerry Dalle -Tezze (HRSA)\nLucia Lee (FDA -CBER)\nRobin Wisch (FDA -CBER)\n13Work group members (CDC)\nAmber Winn\nChris Taylor\nTami Skoff\nAngie Campbell\nMichael Melgar\nAmanda Payne\nNicole Dowling\nNoelle Molinari\nClaire Midgley\nFiona HaversPragna Patel\nAndrea Sharma\nAmadea Britton\nRuth Link -Gelles\nDanielle Moulia\nMegan Wallace\nMonica Godfrey\nKaren Broder\nNaomi Tepper\nHeidi MolineCDC ACIP Staff\nMelinda Wharton\nStephanie Thomas\nJessica MacNeilHannah Rosenblum\nDerrell Powers\nRaigan Wheeler\nSally Ezra\nElizabeth Greene\nManisha Patel\nTom Shimabukuro\nDemorah Hayes\nLatifah BoyceCDC\nKatherine Fleming -Dutra (co -lead)\nJefferson Jones (co -lead)\nMeredith McMorrow\nMila Prill\nNatalie Thornburg\nAron Hall\nIsmael Ortega -Sanchez\nMelissa Coughlin\nJamison Pike\nLauren RoperA. Patricia Wodi\nNeil Murthy\nChristine Olson\nAnne Hause\nAndrew Leidner\nDavid Shay\nSarah Meyer\n14\nFor more information, contact CDC\n1-800 -CDC -INFO (232 -4636)\nTTY:  1 -888 -232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention.\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.", "summary": "1 Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. Maternal/Pediatric Respiratory Syncytial Virus (RSV)  Work Group Sarah S. Long, MD Chair, Maternal/Pediatric RSV Work Group ACIP General Meeting September 22, 2023…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-september-22-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-09-22/01-RSV-Mat-Ped-Long-508.pdf", "doc_date": "2023-09-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 14}
{"title": "02 Mat Peds DeSilva 508", "content": "RSVpreF Vaccine Safety \nSurveillance in Pregnancy from \nThe Vaccine Safety Datalink\nMalini DeSilva, MD, MPH\nACIP meeting\nSeptember 22, 20231\n\nVaccine Safety Datalink (VSD), 2023\n•Collaborative project between \nCDC and integrated healthcare \norganizations\n•Monitors safety of vaccines \nused in the U.S., primarily \nthrough real -world data of \nrare and serious events \nfollowing vaccination\n•Includes data on ~15.5 million \nindividuals across all sites \nannually\n•~ 115,000 annual live births\n•Data is organized using a \ncommon data model with \nstandardized coding systems\n2\nVaccine Safety Datalink (VSD) data structure\n•Distributed data model –each VSD site creates standardized data files\n•Define cohort \n•Vaccines\n•Diagnoses & procedures from inpatient/outpatient/emergency\n•Birth and death files\n•Dynamic pregnancy episode file –validated algorithms for identifying \nongoing & completed pregnancies, updated weekly\n•Pregnancy start, last menstrual period (LMP)\n•Gestational age \n•Pregnancy outcome (when available)\n•Mom -baby linkage\n•Ancillary drug or lab files available ad -hoc for specific studies\n•Automated data files supplemented with chart review, as needed\n3\n4\n\nPrenatal RSVpreF\nVaccine Background\n•RSVpreF (Pfizer) effective against \nsevere RSV -associated LRTI in infants\n•RSVpreF clinical trial data on safety in \npregnant persons\n•Injection site pain most common \nreactogenicity event \n•Imbalance in preterm births in \nvaccinated group\n•Most late preterm (34 –<37 \nweeks)\n•Most occurred >30 days after \nvaccination \n•Most prominent in a single \ncountry \n•GSK RSV prenatal vaccine clinical trial \nhalted due to imbalance in preterm \nbirth in vaccinated5\nGoal & Challenges \nPrenatal RSVpreF Vaccine Surveillance\n•Goal : To evaluate the safety of RSVpreF vaccine administered \nduring pregnancy in the VSD’s large, real -world population \n•Challenges :\n•Vaccine uptake \n•Healthy vaccinee bias\n•Uncertain recommendations for RSVpreF use & administration\n•Coadministration of COVID -19, influenza, Tdap\n6\nPregnancy Outcomes\n7\n1sttrimester 2ndtrimester 3rdtrimester\nLMP\nLMP = Last menstrual periodPregnancy\nPregnancy Outcomes\n8\n1sttrimester 2ndtrimester 3rdtrimester\nLMP 20 weeks 26 weeksNon -viablePeriviable\nPretermTerm\n37 weeksLive Birth\nLMP = Last menstrual periodPregnancy\nPregnancy Outcomes\n9\n1sttrimester 2ndtrimester 3rdtrimester\nLMP 20 weeks 26 weeksNon -viablePeriviable\nPretermTerm\n37 weeksSpontaneous Abortion Stillbirth\nIUFD\nLive Birth\nIUFD = Intrauterine Fetal DemiseLMP = Last menstrual periodPregnancy\nPregnancy Outcomes\n10\n1sttrimester 2ndtrimester 3rdtrimester\nLMP 20 weeks 26 weeksNon -viablePeriviable\nPretermTerm\n37 weeksSpontaneous Abortion Stillbirth\nIUFD\nLive Birth\nIUFD = Intrauterine Fetal DemiseLMP = Last menstrual periodPregnancy\nRSVpreF\n32 weeks\nPregnancy Outcomes\n11\n1sttrimester 2ndtrimester 3rdtrimester\nLMP 20 weeks 26 weeksNon -viablePeriviable\nPretermTerm\n37 weeksSpontaneous Abortion Stillbirth\nIUFD\nLive Birth\nIUFD = Intrauterine Fetal DemiseLMP = Last menstrual periodPregnancy\nRSVpreF\n32 weeks\nPrenatal RSVpreF Surveillance\n•Bimonthly surveillance \n•Use validated algorithms applied to electronic health data in \nVSD to identify pregnant persons 16 –49 years at ≥20 weeks’ \ngestation\n•Exclude pregnancies: ending in therapeutic abortion, multiple \ngestation, and with insufficient information to date pregnancy\n•Exposure: RSVpreF vaccination ≥28 weeks gestation\n•Match 1:1, vaccinated: unvaccinated\n•VSD Site & gestational age\n•Create propensity scores to account for confounding using readily \navailable variables (e.g., age, pregnancy start date, race, ethnicity, \nmedical comorbidities)\n12\n•Acute outcomes\n•Use algorithm developed for other VSD safety surveillance and \nmodified for pregnant population \n•Diagnoses associated with outpatient, emergency department, \nand hospital encounters\n•Chart confirmation for selected outcomes\n•Pregnancy related and birth outcomes\n•Preeclampsia/eclampsia –ICD-10 codes\n•Preterm birth –gestational age at birth\n•Stillbirth –ICD-10 codes with chart review confirmation\n13Adverse outcomes evaluated\nAcute Outcomes\nOutcome Risk window(s) \n(days)VSD Background \nrate/10,000*\nAnaphylaxis 0–1 n/a\nFever 1–7 3.3\nMalaise / fatigue 1–7 11.4\nSkin and soft tissue or local allergic reactions 1–7 7.0\nAcute disseminated encephalomyelitis 1–21, 1–42 0\nAcute myocardial infarction 1–21, 1–42 0.3\nAppendicitis 1–21, 1–42 0.6\nBell's Palsy 1–21, 1–42 0.8\nCerebral venous sinus thrombosis (CVST) 1–21, 1–42 0.1\nDisseminated intravascular coagulation (DIC) 1–21, 1–42 0.3\nGuillain -Barré syndrome 1–21, 1–42 0\nImmune thrombocytopenic purpura (ITP) 1–21, 1–42 7.6\nLymphadenopathy / lymphadenitis 1–21, 1–42 4.6\n14*Identified from unvaccinated pregnant persons, COVID -19 medically attended acute outcomes 1 –7 or 1 –21 day evaluation\nAcute Outcomes, continued\n15Outcome Risk window (d) Background \nrate/10,000*\nMyocarditis / pericarditis 1–21, 1–42 0\nPulmonary embolism (PE) 1–21, 1–42 0.1\nSeizure 1–21, 1–42 0.8\nStevens -Johnson syndrome or toxic epidermal necrolysis 1–21, 1–42 n/a\nStroke, hemorrhagic 1–21, 1–42 0.4\nStroke, ischemic 1–21, 1–42 0.4\nThrombosis with thrombocytopenia syndrome (TTS) 1–21, 1–42 n/a\nThrombotic thrombocytopenic purpura (TTP) 1–21, 1–42 n/a\nTransverse myelitis 1–21, 1–42 n/a\nTrigeminal neuralgia and related disorders 1–21, 1–42 0.1\nVenous thromboembolism (VTE) 1–21, 1–42 0.4\n*Identified from unvaccinated pregnant persons, COVID -19 medically attended acute outcomes 1 -21 day evaluation\nPregnancy related and birth outcomes\n16Outcome Risk window Pfizer phase 3 \nRSVpreF trial, n (%)¥\nPreeclampsia and eclampsia 1-21, 1 -42 68/3682 (1.8)¥\nPreterm birth (<37 w) Up to 37 weeks 126/2494 (5.1)∆\nStillbirth 1-21, 1 -42 10/3682 (0.3)¥\n¥ RSVPreF Phase 3 clinical trial: Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants | NEJM\n∆Preterm birth rate in high -income countries (Slide 23 Evidence to Recommendations Framework: (cdc.gov) )\nPrenatal RSVpreF Surveillance Analysis\n•Risk ratios with corresponding 95% CI using Poisson distribution \nwith robust variance using generalized estimating equation \n(GEE)\n•Censoring within risk windows when no longer at risk, due to \npregnancy outcome, or if an unvaccinated match is vaccinated\n•Adjustments for known confounders\n•If preterm births signal detected, exploration into etiology\n•Sensitivity Analysis: alternative matching strategies\n•Exploratory: Coadministration of Tdap and RSVpreF\n17\nExample timeline\n18Vaccines start 2 months 1stdata pull2-month data lag\n10/1/2023 11/30/2023 1/22/202442-day follow -up\n3/22/2024\nRepeat analyses every 60 days/2 months\nOur Team\nHealthPartners\n•Malini DeSilva\n•Elyse Kharbanda\n•Jacob Haapala\n•Gabriela Vazquez -Benitez\n•Leslie Kuckler\n•Robyn Kaiser\n•Jingyi Zhu\n•Sunita Thapa\n•Sheryl Kane\n•Nicole Trower\n19Weill Cornell Medicine\n•Heather Lipkind\nKaiser Northwest\n•Kimberly Vesco\nCDC\n•Eric Weintraub\n•Elizabeth QuincerOther VSD sites\n•Acumen\n•Denver Health\n•Harvard Pilgrim\n•Indiana University\n•Kaiser Permanente Northwest\n•Kaiser Permanente Colorado\n•Kaiser Permanente Southern \nCalifornia\n•Kaiser Permanente Northern \nCalifornia\n•Kaiser Permanente Washington\n•Kaiser Permanente Mid -Atlantic \nStates\n•Marshfield Clinic\n•OCHIN", "summary": "RSVpreF Vaccine Safety  Surveillance in Pregnancy from  The Vaccine Safety Datalink Malini DeSilva, MD, MPH ACIP meeting September 22, 20231  Vaccine Safety Datalink (VSD), 2023 •Collaborative project between  CDC and integrated healthcare  organizations •Monitors safety of vaccines  used in the U.S., primarily  through real -world data of  rare and serious events  following vaccination •Includes data on ~15.5 million  individuals across all sites  annually •~ 115,000 annual live births •Data…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-september-22-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-09-22/02-Mat-Peds-DeSilva-508.pdf", "doc_date": "2023-09-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 19}
{"title": "03 Mat Peds Moro 508", "content": "Centers for Disease Control and Prevention\nNational Center for Emerging and Zoonotic Infectious Diseases\nMaternal RSV vaccine safety monitoring in the \nVaccine Adverse Event Reporting System (VAERS) \nand V -safe\nPedro L. Moro, MD, MPH\nImmunization Safety Office\nCenters for Disease Control and Prevention (CDC)\nAdvisory Committee for Immunization Practices \nSeptember 22, 2023\n2Co-managed by\nCDC and FDA\nVaccine Adverse Event Reporting System (VAERS)\nVaccine Adverse\nEvent Reporting \nSystem\n+\nhttp://vaers.hhs.gov\n3VAERS\nStrengths\n▪National data \n▪Accepts reports from anyone\n▪Rapidly detects safety signals \n▪Can detect rare adverse events\n▪Data available to publicLimitations\n▪Reporting bias \n▪Inconsistent data quality and completeness\n▪Lack of unvaccinated comparison group\n▪Generally cannot assess causality\n•VAERS accepts all reports from all reporters without making judgments on \ncausality or judging clinical seriousness of the event\n•As a hypothesis generating system, VAERS identifies potential vaccine safety \nconcerns that can be studied in more robust data systems\n4Approaches to analyzing VAERS data\n▪For more than a decade VAERS has been used as part of vaccine safety \nsurveillance for vaccines used in pregnancy (e.g., influenza, Tdap, COVID -19)\n•Descriptive analysis \noClinical review of individual reports \noAggregate descriptions of automated data (e.g., counts of reported adverse events)\noCalculation of reporting rates for pregnancy outcomes (if doses of RSV vaccine \nadministered in pregnancy or vaccination coverage data available are available)\n•Statistical analysis \noHistorical approaches have included data mining; under discussion\n*Reported adverse events are coded using Medical Dictionary for Regulatory Activities terms ( https://www.meddra.org/ )\n5Search for RSV pregnancy reports and clinical review\n▪Search of reports:\n•Specific Medical Dictionary for Regulatory Activities (MedDRA) codes: exposure during \npregnancy, drug exposure during pregnancy, maternal exposure during pregnancy\n•Affirmative answer on Question 8 in VAERS form (pregnancy status)\n•String search of text fields (symptoms, pre -existing illness, medical history) for ‘ preg ’\n▪Medical records requested for ALL pregnancy reports\n▪Clinicians review reports to confirm they are pregnancy reports and \ncategorize the main adverse event/s of interest\n\nVAERS surveillance of adverse events of special interest (AESI) \nafter RSV vaccination\n▪Primary AESIs\n•Selected for historical, theoretical, or observed safety concerns (i.e., in clinical trials)\n•VAERS will obtain medical records for all reports (serious1and non -serious)\n•CDC will review records and abstract clinically important information\n•AESIs may be added to or removed from the list as appropriate\n▪Secondary AESIs\n•Monitored via periodic (e.g., weekly) automated data tables\n•Can be added to primary AESI list if safety concerns identified\n1Based on the Code of Federal Regulations if one of the following is reported: death, life -threatening illness, hospitalization o r prolongation of \nhospitalization , permanent disability, congenital anomaly or birth defect\n6\nAdverse events of special interest (AESI) after RSV vaccines\nPrimary AESIs \n▪Outcomes of general interest \n• Death\n▪Neurologic/neuroinflammatory conditions\n• Guillain -Barre Syndrome (GBS), including Miller \nFisher variant\n• Acute disseminated encephalomyelitis (ADEM)\n• Transverse myelitis (TM)\n• Chronic inflammatory demyelinating \npolyneuropathy (CIDP)\n▪Allergic reactions\n• Anaphylaxis\n▪Cardiac conditions\n•Atrial fibrillation\n•Other supraventricular tachycardias (SVT)Secondary AESI s\n▪Neurologic/neuroinflammatory conditions\n• Optic neuritis\n• Multiple sclerosis\n• Bell’s palsy\n• Encephalitis/Encephalomyelitis\n• Meningitis/Meningoencephalitis\n• Myelitis\n▪ Other conditions\n• Vaccination errors\n• AEs following simultaneous administration with \nCOVID -19, inactivated influenza, or other adult \nvaccinesWill be monitored in VAERS for all RSV vaccines, including for reports among pregnant persons\n8Pregnancy -specific outcomes to be monitored in \nVAERS and abstracted after maternal RSV vaccine \n▪Pregnancy reports after maternal RSV vaccine\n•Premature/preterm birth\n•Stillbirth\n•Spontaneous abortion\n•Gestational diabetes\n•Preeclampsia/eclampsia/gestational hypertension\n•Birth defects\n•Maternal and infant deaths\n•Other selected adverse infant outcomes/AEs\n9▪New version of V -safe developed starting Summer 2023\n•Leverages existing CDC IT infrastructure\n•Includes email and text messaging options\n•First use for RSV vaccines received by persons aged 60 and older\n•Use for maternal RSV vaccines planned for later this fall\n▪V-safe objectives:\n1. Characterize local and systemic reactogenicity during days 0 -7 after vaccination\n2. Characterize health impacts during a 6 -week post -vaccination follow -up period\n3. Identify participants who report medically attended events after vaccination and \nencourage completion of a VAERS report\n\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the \nofficial position of the Centers for Disease Control and Prevention.Thank you", "summary": "Centers for Disease Control and Prevention National Center for Emerging and Zoonotic Infectious Diseases Maternal RSV vaccine safety monitoring in the  Vaccine Adverse Event Reporting System (VAERS)  and V -safe Pedro L. Moro, MD, MPH Immunization Safety Office Centers for Disease Control and Prevention (CDC) Advisory Committee for Immunization Practices  September 22, 2023 2Co-managed by CDC and FDA Vaccine Adverse Event Reporting System (VAERS) Vaccine Adverse Event Reporting  System +…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-september-22-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-09-22/03-Mat-Peds-Moro-508.pdf", "doc_date": "2023-09-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 10}
{"title": "04 Mat Peds Hutton 508", "content": "Economic Analysis of RSVpreF\nMaternal Vaccination\nDavid W. Hutton, PhD, MS\nProfessor, Health Management and Policy, School of Public Health\nProfessor of Global Public Health, School of Public Health\nProfessor, Industrial and Operations Engineering, College of Engineering\nUniversity of MichiganSeptember 22, 2023\n\nResearch team\nUniversity of Michigan\n•David Hutton, PhD\n•Lisa Prosser, PhD\n•Angela Rose, MPH\n•Kerra Mercon , MSCDC\n•Jefferson Jones, MD, MPH, FAAP\n•Mila Prill, MSPH\n•Meredith McMorrow, MD, MPH, FAAP\n•Jamison Pike, PhD\n•Katherine Fleming -Dutra, MD, FAAP\n•Ismael Ortega -Sanchez, PhD\n•Fiona Havers, MD\n•Betsy Gunnels, MSPH\n•Andrew Leidner , PhD\n2\nConflicts of interest statements\n•Authors have no known conflict of interests.\n3\n•Additional vaccine efficacy scenario\n•Additional timing scenarios\n•Months of year to administer\n•32 Τ07-36 Τ67weeks gestation\n•Updated cost/doseUpdates Since June 21 Presentation\nEconomic Analysis of RSV Vaccination in Older Adults, June 21, 2023\n0%20%40%60%80%100%\n0 3 6 9 12Efficacy\nMonth\nAgainst medically-attended RSV-associated LRTI Against hospitalization\n5Methods: RSVpreF efficacy\naverage 6 -month efficacy = efficacy against \nhospitalization or medically -attended RSV -\nassociated LRTI\nZero efficacy\nSource: Kampmann et al 2023\nLRTI= Lower respiratory tract infection\n0%20%40%60%80%100%\n0 3 6 9 12Efficacy\nMonth\nAgainst medically-attended RSV-associated LRTI Against hospitalization\n6Methods: RSVpreF efficacy\nalternate flat scenario\nZero efficacy\nSource: Kampmann et al 2023\nLRTI= Lower respiratory tract infectionaverage 6 -month efficacy = efficacy against \nhospitalization or medically -attended RSV -\nassociated LRTI\n0%20%40%60%80%100%\n0 3 6 9 12Efficacy\nMonth\nsevere MA RSV LRTI MA RSV LRTI\n7Methods: RSVpreF efficacy\nOptimistic scenario: Severe Efficacy with VE to 9 months\n6-month efficacy against \nSevere MA RSV LRTI\nZero efficacy \nat 9 months6-month efficacy against \nMA RSV LRTI\nMA: Medically -attended, LRTI: Lower Respiratory Tract Infection\nMethods: Provision of RSVpreF\n8•Base case:\n•Year round\n•Scenarios\n•Individual Months\n•Ranges of Months\n•April -February\n•May -February\n•June -February\n•August -January\n•September -January\n•September -December\n•Mother vaccinated \n•During 32 Τ07-36 Τ67weeks gestation, evenly distributed\n•Birth \n•Must be >2 weeks after vaccination for protective efficacy to pass to infant, \nbased on historical gestational age\n9Methods: Provision of RSVpreF\nMethods: Provision of RSVpreF\n10In Time= >2 weeks prior to delivery100 Pregnant persons50 \nNo intention\n50 \nIntend to Vaccinate\n45 \nVaccinated\nin time2 \nBirth before vaccinationUptake\nTiming48\nVaccinated3 \nVaccinated < 2 weeks \nbefore delivery\nResults: Base case\n11•Base case:\n•Population of annual US births ( 3.66 million )\n•50% intended uptake in the RSVpreF group\n•First RSV season\n•$295/dose\n•RSVpreF only impacts lower respiratory tract infections\nResults: Number Needed to Vaccinate\n12Cohort: 3.66 million births, assuming 50% intended uptake in RSVpreF group40 115 242 1,100 \n45 367 \n - 200 400 600 800 1,000 1,200\nOutpatient ED Inpatient ICU Inpatient Day ICU DayNumber needed to Vaccinate to avoid\nRSVPreF\nResults: Costs\n13Base costs of RSVpreF : $295/dose, both natural history and RSVPreF involve palivizumab for high -risk childrenCohort: 3.66 million births, assuming 50% intended uptake in RSVpreF group$0$500$1,000$1,500$2,000$2,500\nNatural\nHistoryRSVPreF Natural\nHistoryRSVPreF Natural\nHistoryRSVPreF Natural\nHistoryRSVPreF Natural\nHistoryRSVPreF Natural\nHistoryRSVPreF\nIntervention Outpatient ED Inpatient Deaths TotalTotal Costs in Cohort\nMillions\nMedical Productivity\nResults: Cost per Event Averted\n14Base costs of RSVpreF : $295/dose$11,337 $32,652 $68,423 $311,013 \n$12,671 $103,671 \n $- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000\nOutpatient ED Inpatient ICU Inpatient Day ICU DayCost per Event Averted\nRSVPreF\nResults: Cost -Effectiveness\n15Base costs of RSVpreF : $295/dose\nQALY= quality -adjusted life -year; ICER= incremental cost -effectiveness ratioCohort: 3.66 million births, assuming 50% intended uptake in RSVpreF group, ICER is not affected by uptakeOverallCosts ($) QALYs lostICER ($/QALY)\nVs. NH\nNatural History 1,585,172,002 18,151 \nRSVpreF 2,103,215,047 16,857 400,304 \n$0 $100,000 $200,000 $300,000 $400,000 $500,000 $600,000 $700,000 $800,000\nProbability of Prematurity\nRSV QALYS Lost\nRSVpreF vaccine cost/dose\nDisease-specific inpatient costs (per inpatient case)\nVaccination Efficacy, Hospitalized RSV LRTI through 180 days\nVaccination Efficacy, RSV MA-LRTI through 180 days\nProportion of RSV infections with an LRTI diagnosis Outpatient Age 0-5 months\nProportion of RSV infections with an LRTI diagnosis ED Visits Age 0-5 months\nProportion of RSV infections with an LRTI diagnosis Hospitalizations Age 0-5 months\nRSV mortality per hospitalization Age 0-5 monthsIncremental Cost -Effectiveness Ratio\nLow HighSensitivity: Tornado RSVpreF\n16Base cost of RSVpreF : $295/dose\nMA= Medically -attended\nLRTI= Lower respiratory tract infection\nQALY= Quality adjusted life year$1.3 million\nMethods: RSVpreF efficacy\n“flat efficacy” scenario\n17Overall Costs ($) QALYs lost ICER ($/QALY)\nNatural History 1,585,172,002 18,151 \nRSVpreF 2,094,993,469 16,757 365,669 \nSlightly lower costs with \nRSVpreF , slightly fewer \nQALYs lost, slightly lower \nICER\nICER: Incremental cost -effectiveness ratio\nLRTI= Lower respiratory tract infection\n\nSensitivity Analysis: More Optimistic Efficacy\n18Base costs of RSVpreF : $295/dose\nQALY= quality -adjusted life -year; ICER= incremental cost -effectiveness ratioCohort: 3.66 million births, assuming 50% intended uptake in RSVpreF group, ICER is not affected by uptakeOverallCosts ($) QALYs lostICER ($/QALY)\nVs. NH\nNatural History 1,585,172,002 18,151 \nRSVpreF 2,056,423,553 16,504 286,179 \nHigher and longer efficacy\nMA: Medically -attended, LRTI: Lower Respiratory Tract Infection\n19Sensitivity: Varying Efficacy, Hospitalization Cost, and \nMortality\nBase$0$100,000$200,000$300,000$400,000$500,000\n$0 $10,000 $20,000 $30,000 $40,000 $50,000 $60,000ICER\nHospitalization Cost\n0.1% Mortality, Base Efficacy 0.1% Mortality, Optimistic Efficacy\n1.0% Mortality, Base Efficacy 1.0% Mortality, Optimistic Efficacy\n $- $100,000 $200,000 $300,000 $400,000 $500,000 $600,000 $700,000 $800,000\n$0 $50 $100 $150 $200 $250 $300 $350 $400 $450 $500ICER\nCost per dose of RSVpreFSensitivity: Cost RSVpreF\n20Base Case\nResults: RSVpreF timing scenarios\n21•Scenarios\n•Base: vaccine given year -round\n•By Month\n•During April -February\n•During May -February\n•During June -February\n•During August -January\n•During September -January\n•During September -December\nResults: RSVpreF timing scenarios\n$351,238 $333,255 \n$181,649 \n$115,445 $111,248 $174,344 \n $- $100,000 $200,000 $300,000 $400,000 $500,000\nJan Feb Mar Apr May Jun Jul Aug Sep Oct Nov DecICER ($.QALY)ICER: RSVpreF vs. Natural History\n22Month of administration\nResults: RSVpreF timing scenarios\n$400,304 \n$363,344 \n$322,594 \n$282,498 \n$186,256 $167,280 $141,806 \n $- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000 $450,000\nBase Apr-Feb May-Feb Jun-Feb Aug-Jan Sep-Jan Sep-DecICER ($.QALY)ICER: RSVpreF vs. Natural History\n23\nLimitations\n•Model Structure\n•No risk groups\n•No dynamic transmission. No impact of the vaccine on transmission and \nindirect effects\n•Uncertain inputs\n•RSVpreF cost \n•QALYs lost \n•Upper respiratory tract infections\n•Prematurity\n•Assumption: no infants will be receiving nirsevimab\n24\nSummary\n•RSVpreF may improve RSV outcomes, but will also increase costs\n•RSVpreF has the potential to be cost -effective\n•Results sensitive to:\n•Rate of prematurity \n•Cost per dose (~65,000 –68$/QALY)\n•Hospitalization Costs (Cost -saving –440,000 $/QALY)\n•Efficacy (~280,000 –680,000 $/QALY)\n•QALYs lost (~100,000 –800,000 $/QALY)\n•Month of Administration (~110,000 –Millions $/QALY)\n25QALY: Quality -Adjusted Life -Year\nEconomics of combined use of Pfizer \nmaternal RSVpreF vaccine and \nnirsevimab\nDavid W. Hutton, PhD, MS\nProfessor, Health Management and Policy, School of Public Health\nProfessor of Global Public Health, School of Public Health\nProfessor, Industrial and Operations Engineering, College of Engineering\nUniversity of MichiganSeptember 22, 2023\n\n•On August 3, 2023, the Advisory Committee on Immunization \nPractices (ACIP) recommended use of nirsevimab\n•How should we think about combinations of RSVpreF and \nnirsevimab ?\n•If we know RSVpreF has been administered in time, how cost -effective is it to \nprovide nirsevimab ?\n•If we know the infant will receive nirsevimab , how cost -effective is it to \nprovide RSVpreF ?Methods: Study questions\n•RSVpreF will be administered in weeks 32 -36\n•Because of this, we are assuming the infant is full -term, and therefore, there is no need for \npalivizumab for any newborns considered in this analysis\n•Consideration of higher -risk populations (but assuming they are not premature)\n•New timing of RSVpreF administrationUpdates since June\nMethods: Intervention effectiveness\n•NO evidence of efficacy on the combined use of these products\n•Assumption:\n•Efficacy equal to the highest of nirsevimab or RSVpreF :\n•Efficacy would not be higher than from the most effective product\n29\n0%20%40%60%80%100%\n0 2 4 6 8 10 12 14Hospitalization Efficacy\nMonths since birth\nRSVPreF Both NirsevimabMethods: Intervention effectiveness\n30\nAdditional benefit of adding nirsevimab\n* Assuming administration of nirsevimab at birth\n\n0%10%20%30%40%50%60%70%80%90%100%\n0 2 4 6 8 10 12Hospitalization Efficacy\nMonth\nBoth RSVpreF OnlyMethods: Intervention effectiveness\nExample: Off -peak (Aug) birth\nAdditional benefit of adding nirsevimab\nNote: Peak infections are typically Dec -Feb\n 31\nIncremental benefit of adding nirsevimab on top of \nRSVpreF\n32•For infants of persons vaccinated with RSVpreF during pregnancy at \nleast 2 weeks prior to delivery\nResults: Incremental benefit of adding nirsevimab\non top of RSVpreF : Higher Risk\n•Higher -Risk\n•Increased multiplier on \n•risk of hospitalization \n•No change in\n•Outpatient incidence\n•ED incidence\n•Cost/outcome\n•QALYs/outcome\n33\nResults: Incremental benefit of adding nirsevimab\non top of RSVpreF : By Month and Risk\n $- $200,000 $400,000 $600,000 $800,000 $1,000,000 $1,200,000 $1,400,000 $1,600,000 $1,800,000ICER\n1x 2x 3x 6x 10x\n34Nirsevimab given in Oct -Mar\nICER= Incremental cost effectiveness ratio ($/QALY)\nIf the 10x bars are “missing”, providing nirsevimab is cost -saving.Birth Month\nRisk LevelNirsevimab given at birth Nirsevimab given Oct/Nov\nResults: Incremental benefit of adding nirsevimab\non top of RSVpreF : By Month and Risk\n $- $50,000 $100,000 $150,000 $200,000 $250,000ICER\n3x 6x 10x\n35Nirsevimab given in Oct -Mar\nICER= Incremental cost effectiveness ratio ($/QALY)\nIf the 10x bars are “missing”, providing nirsevimab is cost -saving.Birth Month\nRisk LevelNirsevimab given at birth Nirsevimab given Oct/Nov\nResults: Adding nirsevimab to allinfants born year -\nround to vaccinated mothers\n - 200 400 600 800 1,000 1,200 1,400\nOutpatient ED Inpatient ICU Inpatient Day ICU DayNumber Needed to Immunize to \nAvoid One…\n1x 2x 3x 6x 10x\n36Nirsevimab given at birth for babies born October -March, and in October/November for babies born in April through \nSeptember to mothers who received RSVpreF at least 2 weeks prior to delivery\nResults: Adding nirsevimab to allinfants born year -\nround to vaccinated mothers\n37Notes: Nirsevimab given at birth for babies born October -March, and in October/November for babies born in April through September to \nmothers who received RSVpreF at least 2 weeks prior to delivery\nICER= Incremental cost effectiveness ratio; QALY= Quality -adjusted life -year$413,035 \n$282,083 \n$192,782 \n$40,256 \n $- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000 $450,000\nICERICER\n1x 2x 3x 6x 10xCost -Saving\nNirsevimab given in October/November for babies born in April through September born to mothers who received \nRSVpreF at least 2 weeks prior to deliveryResults: Adding nirsevimab at the start of the \nseason only for infants born Apr-Sept\n - 200 400 600 800 1,000 1,200\nOutpatient ED Inpatient ICU Inpatient Day ICU DayNumber Needed to Immunize to \nAvoid One…\n1x 2x 3x 6x 10x\n38\nNirsevimab given in October/November for babies born in April through September born to mothers who received \nRSVpreF at least 2 weeks prior to delivery\nICER= Incremental cost effectiveness ratio; QALY= Quality -adjusted life -yearResults: Adding nirsevimab at the start of the \nseason only for infants born Apr-Sept\n39$305,182 \n$203,194 \n$131,505 \n$4,830 \n $- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000ICER\n1x 2x 3x 6x 10xCost -Saving\nNirsevimab given in October/November for babies born in April through September born to mothers who received \nRSVpreF at least 2 weeks prior to deliveryResults: Adding nirsevimab during the season for \ninfants born Oct-Mar\n - 200 400 600 800 1,000 1,200 1,400 1,600\nOutpatient ED Inpatient ICU Inpatient Day ICU DayNumber Needed to Immunize to \nAvoid One…\n1x 2x 3x 6x 10x\n40\nNirsevimab given in October/November for babies born in April through September born to mothers who received \nRSVpreF at least 2 weeks prior to delivery\nICER= Incremental cost effectiveness ratio; QALY= Quality -adjusted life -yearResults: Adding nirsevimab during the season for \ninfants born Oct-Mar\n41$606,362 \n$416,695 \n$293,926 \n$95,537 \n $- $100,000 $200,000 $300,000 $400,000 $500,000 $600,000 $700,000ICER\n1x 2x 3x 6x 10xCost -Saving\n•Additional benefit beyond RSVpreF protection\n•ICERs are high, but could be lower for higher -risk populations, \nparticularly if born off -peakSummary: Incremental benefit of \nadding nirsevimab on top of RSVpreF\n42\nIncremental benefit of adding RSVpreF on top of \nnirsevimab\n•If you know the infant will be receiving nirsevimab\n43\nResults: Incremental benefit of adding RSVpreF on \ntop of nirsevimab\n$2.4 $6.0 $9.4 \n$5.0 \n$3.6 \n $- $1.0 $2.0 $3.0 $4.0 $5.0 $6.0 $7.0 $8.0 $9.0 $10.0ICER (Millions)\n44Birth Month\nICER= Incremental cost effectiveness ratio\nSummary: Incremental benefit of adding RSVpreF\non top of nirsevimab\n•Very marginal additional benefit beyond nirsevimab protection\n•ICERs are extremely high\n45\nOverall summary: Combinations\n•Limitation:\n•No efficacy data for combination of products\n•Nirsevimab may add additional protection on top of RSVpreF , \nparticularly for higher -risk infants.\n•Adding RSVpreF on top of nirsevimab adds marginal effectiveness at \nvery high cost in the general population\n46\nThank You\n•Please send comments to:\n•dwhutton@umich.edu\n47\nAppendix to Economics of Pfizer maternal \nRSVpreF vaccine\n48\nResearch team\nUniversity of Michigan\n•David Hutton, PhD\n•Lisa Prosser, PhD\n•Angela Rose, MPH\n•Kerra Mercon , MSCDC\n•Jefferson Jones, MD, MPH, FAAP\n•Mila Prill, MSPH\n•Meredith McMorrow, MD, MPH, FAAP\n•Jamison Pike, PhD\n•Katherine Fleming -Dutra, MD, FAAP\n•Ismael Ortega -Sanchez, PhD\n•Fiona Havers, MD\n•Betsy Gunnels, MSPH\n•Andrew Leidner , PhD\n49\nConflicts of interest statements\n•Authors have no known conflict of interests.\n50\nMethods: Study question\n•Determine the cost -effectiveness of RSVpreF by:\n•Evaluating the population impact in terms of \n•annual resource utilization \n•total cases\n•total costs \n•deaths\n•quality -adjusted life -years (QALYs)\n•Comparing the incremental cost -effectiveness ratio (ICER) of RSVpreF to natural history/no \nvaccine.\n•Running scenario analyses outcomes that explore key areas of uncertainty.\n•Perspective: Societal\n51\nMethods: Intervention(s)\n•Target population: US pregnant persons\n•Interventions:\n1.No vaccination (Natural history)\n2.RSVpreF against RSV illness\n•Timeframe: 1 year (1 RSV season)\n•Analytic horizon: infant’s lifetime\n•Discount rate: 3%\n52\nMethods: Decision tree model\n53Natural\nHistory\nRSVpreFInfection Hospitalization\nED\nNone of the aboveOutpatientAlive\nDeadInfection\nAdverse \nEventsPrematurity\nInjection site reaction\nNone of the aboveSerious adverse eventInfection Infection\nMethods: Epidemiology\nHospitalization\n54Base Case Range Source\nRespiratory syncytial virus (RSV) \nincidence, per 100,000 See Above See AboveCDC NVSN, \nDecember 2016 to September 2020\nProportion with LRTI\nAge 0 -5 months 1.0 0.5-1.0 Rainisch, 2020\nAge 6 -11 months 1.0 0.5-1.0 Rainisch , 2020\nCDC New Vaccine Surveillance Network (NVSN) hospitalization rates for children under 2 years of age from December 2016 to Sep tember 2020 - 1,000 2,000 3,000 4,000\n0 2 4 6 8 10 12 14 16 18 20 22Hospitalization rate  \nper 100,000 \nchildren\nAge in months\nMethods: Epidemiology\nED and Outpatient\n55Respiratory syncytial virus (RSV) \nincidence, per 100,000 Base Case Range Source\nEmergency Department\nAge 0 -5 months 7,500 5,500 –7,500 Lively 2019 (base case and range), Hall \n2009 (range)\nAge 6 -11 months 5,800 5,700 –5,800 Lively 2019 (base case and range), Hall \n2009 (range)\nAge 12 -23 months 3,200 3,200 –5,300 Hall 2009 (base case and range), Lively \n2019 (range)\nProportion with LRTI\nAge 0 -5 months 0.65 0.25 -1.0 Rainisch , 2020\nAge 6 -11 months 0.5 0.25 -1.0 Rainisch , 2020\nOutpatient\nAge 0 -5 months21,60013,200 –21,600 Lively 2019 (base case and range), Hall \n2009 (range)\nAge 6 -11 months24,60017,700 –24,600 Lively 2019 (base case and range), Hall \n2009 (range)\nAge 12 -23 months18,4406,600 –29,620 Jackson 2021 (base case and range), \nHall 2009 (range)\nProportion with LRTI\nAge 0 -5 months 0.65 0.25 -1.0 Rainisch , 2020\nAge 6 -11 months 0.3 0.1-1.0 Rainisch , 2020\nLRTI= Lower respiratory tract infection\nMethods: Epidemiology\nMortality\n56Base \nCaseRange Source\nRSV mortality per \nhospitalization\nAge 0 -5 months 0.10%0.04 -0.20%Hansen 2022, \nDoucette 2016\nAge 6 -11 months 0.10%0.04 -0.20%Hansen 2022, \nDoucette 2016\nAge 12 -23 months 0.3% 0.28% -0.34% Gupta 2016\nSeasonality\n570%5%10%15%20%25%30%\nApr May Jun Jul Aug Sep Oct Nov Dec Jan Feb MarFraction of Annual Infections\nSource: National Respiratory and Enteric Virus Surveillance System (NREVSS) (2015 -2019)\nMethods: Efficacy\n58Variable Base case \nvalueRange for \nsensitivity \nanalysisSource\nRSVpreF\nInitial efficacy (months 0 -5) \nagainst medically -attended \nRSV-associated LRTI 51.3% 29.4% -66.8%Kampmann\net al, 2023\nInitial efficacy (months 0 -5) \nagainst hospitalized RSV -\nassociated LRTI 56.8% 10.1% -80.7%Kampmann\net al, 2023\nEfficacy months 6 -12 0\nAssumed 0% efficacy against upper respiratory tract infections\nLRTI= Lower respiratory tract infection\nMethods: Medical Costs\nVariable Value Range Source\nDisease -specific \nhospitalization costs (per \nhospitalization) \nAge 0 -11 months $11,487 4,804 -86,646\nBowser 2022Age 12 -23 months $11,469 4,804 -86,646\nDisease -specific ED costs \n(per ED visit)$563 544 -581 Bowser 2022\nDisease -specific \noutpatient costs (per \noutpatient visit)$82 46 -118 Bowser 2022\n59•Bowser, 2022 is a systematic review using studies from 2014 -2021\n•Funded by Sanofi\n•All numbers updated to 2022 dollars using GDP Deflator\nMethods: Productivity costs\nVariable Value Range Source\nProductivity burden of RSV \ndisease (caregiver losses)\nDays of lost productivity\nOutpatient* 2.5 0-5Fragaszy, 2018; Petrie, 2016; \nVan Wormer, 2017\nED* 2.5 0-5Fragaszy, 2018; Petrie, 2016; \nVan Wormer, 2017\nHospitalization^ 7.4 0-14\nLifetime productivity for \nthose <1 year old (lost from \ndeath)1,795,936 1,346,951 -\n2,244,919Grosse, 2019\n60*Productivity for outpatient and ED based on adult influenza\n^Hospitalization productivity loss = length of hospitalization + 2 days\nMethods: Intervention cost\nVariable Value Range Source\nImmunization -related costs\nRSVpreF , per dose $295 50 –500Assumption: Manufacturer \ncosts for adult vaccine\nRSVpreF administration $16.96 15 -22 Medicare: HCPCS 90460\n61Both assume no additional visits, but do include costs of administration\nMethods: Adverse event costs\nVariable Value Range Source\nRSVpreF Maternal Adverse \nEvents\nRate of injection site reaction 0.41 0.38 –0.44 Pfizer Phase 3 Trial\nProbability of healthcare \nvisit, given injection site \nreaction0.02 0.015 –0.025 Curran, 2020\nCost of outpatient visit $367.76 23.15 –1,758 (Deluca, 2023)\nRecipient time, physician \noffice for injection site \nreaction (hours)2 1 -3 Assumption \nHypothetical serious \nadverse event0.000001 0 -0.0002Base: Prosser, 2006\nHigh: 95% CI Phase 3 data for \nRSV adult vaccines\n62\n63Kampmann B, Madhi SA, Munjal I, Simões EA, Pahud BA, Llapur C, Baker J, Pérez Marc G, Radley D, Shittu E, Glanternik J. \nBivalent prefusion F vaccine in pregnancy to prevent RSV illness in infants. New England Journal of Medicine. 2023 Apr 5.Methods: Prematurity?\n1% Difference?\n\nMethods: Prematurity scenario\nVariable Value Range Source\nRSVpreF infant adverse \nevents\nHigher Rate of Prematurity 0% 0-2% Pfizer Phase 3 Trial\n64 * All costs updated to 2022 using GDP DeflatorOutcomes, per prematurity\nLifetime cost of late \nprematurity\nMedical $ 23,241 $11,621 –\n$46,482 Waitzman , Jalali, Grosse, 2021\nProductivity $ 11,447 $5,724 –\n$22,894 Waitzman , Jalali, Grosse, 2021\nQALYs lost from late \nprematurity0.03 0 –1.2Werner, Hauspurg , Rouse, 2015\nPetrini et al, 2008, Hirvonen et al, 2014, Crump \net al, 2021, Darcy -Mahoney et al, 2016, Carroll \net al, 2009, Payakachat et al, 2014\nMethods: RSV \nhealth -related quality of life\n65LRTI quality -adjusted life DAYS lost Base Lower (Regnier) Upper (JIVE)\nOutpatient: Child 3.1 1.8 16.6\nOutpatient: Caregiver 1.5 0 9.1\nED: Child 4.9 2.9 16.6\nED: Caregiver 2.5 0 9.1\nHospitalized: Child 6.2 3.7 26.5\nHospitalized: Caregiver 2.4 0 13.6Measured in \nDays Lost\nMost \nLikely\nMethods: Epidemiological model\nSeasonalityIncidence\n•Outpatient\n•ED\n•Hospitalizations\nNirsevimab\nWaning \nProtectionHealth Effects\n• Outpatient\n• ED\n• Hospitalizations\n• Deaths\nEconomic Effects\n• Intervention\n• Disease\n• Societal\n• QALYs\n• ICERInterventionsEpidemiology\nTiming\nCost Burden/\n•Outpatient\n•ED\n•HospitalizationsHealth Economics\nHealth Burden/\n•Outpatient\n•ED\n•Hospitalizations\n66\nMethods: Inputs\n•Incidence\n•Raw reported incidence may be underreported because of imperfect PCR \nsensitivity, so we consider an additional scenario in sensitivity analysis:\n•based on CDC Unpublished re -analysis of raw data from Zhang et al study which found \ndecreased RSV PCR sensitivity in light of paired serology testing (adjustment factor: \n87.6%).\n67\nHealth -Related Quality -of-Life\n•Sources\n•Glaser (2022)\n•Estimate based on comparison of utility losses between premature children who had RSV vs. \npremature children without RSV and their caregivers\n•Used as base case for hospitalization for children and their caregivers\n•Regnier (2013) \n•Estimate QALY losses for hospitalization, ED visits, and outpatient visits for children with \npertussis \n•Use relative QALYs between hospitalization, ED, and outpatient to estimate base losses for ED \nand outpatient in base case\n•JIVE RSV Utilities Survey (2021)\n•Estimates QALY losses for hospitalization and outpatient visits for child and caregiver\n•Estimates may be impacted by COVID -related concerns about respiratory viruses\n•Inform upper bound of range\n68\n69Timing of those who received vaccination during pregnancy\nRSVpreF is assumed to start earlier at week 24 (vs. week 27)Methods: Provision of RSVpreF\n00.050.10.150.20.25\n1 3 5 7 911 13 15 17 19 21 23 25 27 29 31 33 35 37 39Fraction Vaccinated (given receipt \nof vaccine)\nGestational Age\nReported Tdap Modeled RSVpreF vaccination timing\n700.0%5.0%10.0%15.0%20.0%25.0%30.0%35.0%40.0%45.0%\n0 10 20 30 40 50\nGestational Age (Week)\nSource: NCHS from 2019 and 2021Methods: Birth Timing\nValidation\n231\n66\n8225 \n65 \n13 \n050100150200250\nOutpatient Clinic\nVisitsED Visits HospitalizationsRates of Medically -Attended RSV \n(per 1000 births)\nRainisch et al, Vaccine, 2020 JIVE model\n71\nMethods: Maternal Adverse Event Health Effects\nVariable Value Range Source\nAdult Quality -Adjusted Life -\nYears lost due to adverse events\nInjection Site Reaction 0 Assumed\nSerious Adverse Event 0.141 0.092 -0.199 Prosser, 2006\n72\nResults: Health outcomes\n73Cohort: 3.66 million births, assuming 50% intended uptake in RSVpreF group\nURTI= upper respiratory tract infection; LRTI= lower respiratory tract infection - 100,000 200,000 300,000 400,000 500,000 600,000 700,000 800,000 900,000\nNatural\nHistoryRSVpreF Natural\nHistoryRSVpreF Natural\nHistoryRSVpreF\nOutpatient Emergency Department InpatientNumber of Events in Cohort\nURTI LRTI\nResults: Events Averted\n74Cohort: 3.66 million births, assuming 50% intended uptake in RSVpreF group45,693\n15,866\n7,571\n1,66640,884\n4,997\n05,00010,00015,00020,00025,00030,00035,00040,00045,00050,000\nOutpatient ED Inpatient ICU Inpatient Day ICU DayEvents Averted per Year\nRSVPreF\nResults: QALYs Lost\n75Adverse \nEventsOutpatient ED Inpatient Deaths Total Grand\nChild Caregiver Child Caregiver Child Caregiver Child Child Caregiver Total\nNatural \nHistory 7,153 3,580 3,290 1,645 807 320 1,356 12,606 5,545 18,151 \nRSVpreF 0.2495 6,766 3,387 3,075 1,538 679 269 1,141 11,663 5,194 16,857 \nCohort: 3.66 million births, assuming 50% intended uptake in RSVpreF group\nQALY= quality -adjusted life -year\n76Sensitivity: Hospitalization Mortality\nBase$0$50,000$100,000$150,000$200,000$250,000$300,000$350,000$400,000$450,000$500,000\n0.00% 0.20% 0.40% 0.60% 0.80% 1.00% 1.20%ICER\nHospitalized Mortality\nScenario: Prematurity\n77Base Case\n $- $200,000 $400,000 $600,000 $800,000 $1,000,000 $1,200,000 $1,400,000 $1,600,000\n0.0% 0.5% 1.0% 1.5% 2.0%ICER\nExcess Prematurity\nScenario: Upper Respiratory Tract Infection Effect\n78RSVpreF is assumed to have 37.9% efficacy for upper respiratory tract infections based on overall respiratory tract \nefficacy from phase 3 trial ( Kampmann , 2023)\nICER= incremental cost effectiveness ratio; QALY= Quality adjusted life year$279,490/QALY\n $- $100,000 $200,000 $300,000 $400,000 $500,000 $600,000\n$0 $50 $100 $150 $200 $250 $300 $350 $400 $450 $500ICER\nTotal Cost of RSVpreF\nAppendix to Economics of combined use of Pfizer \nmaternal RSVpreF vaccine and nirsevimab\n79\nMethods: Study questions\n•Determine the cost -effectiveness of:\n•Nirsevimab in children born to mothers who received RSVpreF at least 2 weeks prior to \ndelivery\n•RSVpreF for pregnant persons who will give nirsevimab to their newborns\n•Single individual\n•Evaluate by month of year\n•Perspective: Societal\n•Timeframe: 1 year (1 RSV season)\n•Analytic horizon: infant’s lifetime\n•Discount rate: 3%\n80\n810.0%5.0%10.0%15.0%20.0%25.0%30.0%\nApr May Jun Jul Aug Sep Oct Nov Dec Jan Feb MarFraction of Annual Infections\nSource: National Respiratory and Enteric Virus Surveillance System (NREVSS) (2015 -2019)Reminder: Seasonality\nMethods: Intervention effectiveness\n82* Assuming administration of nirsevimab at birth0%20%40%60%80%100%\n0 2 4 6 8 10 12 14Hospitalization Efficacy\nMonths since birth\nRSVPreF Both Nirsevimab\n0%20%40%60%80%100%\n0 2 4 6 8 10 12 14Hospitalization Efficacy\nMonths since birth\nRSVPreF Both NirsevimabMethods: Intervention effectiveness\n83\nAdditional benefit of adding RSVpreF\n* Assuming administration of nirsevimab at birth\n0%10%20%30%40%50%60%70%80%90%100%\n0 2 4 6 8 10 12Hospitalization Efficacy\nMonth\nBoth Nirsevimab OnlyMethods: Intervention effectiveness\nexample: Off -peak (Aug) birth\nAdditional benefit of adding RSVpreF\n84\n\nResults: Adding nirsevimab to allinfants born to \nvaccinated mothers\n0.00000.05000.10000.15000.20000.2500\nOutpatient ED Inpatient ICU Inpatient Day ICU DayAdditional Events Averted Per \nInfant Given Nirsevimab\n1x 2x 3x 6x 10x\n85Nirsevimab given at birth for infants born October -March, and in October/November for infants born in April through \nSeptember\nResults: Adding nirsevimab at the start of the \nseason only for infants born Apr-Sept\n0.00000.05000.10000.15000.20000.25000.3000\nOutpatient ED Inpatient ICU Inpatient Day ICU DayAdditional Events Averted Per \nInfant Given Nirsevimab\n1x 2x 3x 6x 10x\n86Nirsevimab given in October/November for babies born in April through September born to mothers who received \nRSVpreF\nResults: Adding nirsevimab during the season for \ninfants born Oct-Mar\n0.00000.05000.10000.15000.2000\nOutpatient ED Inpatient ICU Inpatient Day ICU DayAdditional Events Averted Per \nInfant Given Nirsevimab\n1x 2x 3x 6x 10x\n87Nirsevimab given in October/November for babies born in April through September born to mothers who received \nRSVpreF", "summary": "Economic Analysis of RSVpreF Maternal Vaccination David W. Hutton, PhD, MS Professor, Health Management and Policy, School of Public Health Professor of Global Public Health, School of Public Health Professor, Industrial and Operations Engineering, College of Engineering University of MichiganSeptember 22, 2023  Research team University of Michigan •David Hutton, PhD •Lisa Prosser, PhD •Angela Rose, MPH •Kerra Mercon , MSCDC •Jefferson Jones, MD, MPH, FAAP •Mila Prill, MSPH •Meredith McMorrow,…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-september-22-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-09-22/04-Mat-Peds-Hutton-508.pdf", "doc_date": "2023-09-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 87}
{"title": "05 Mat Peds Ortega Sanchez 508", "content": "Economics of Preventing Respiratory Syncytial \nVirus Disease among US Infants by Maternal \nVaccination Prior to Birth\nA SUMMARY REPORT COMPARING MODELS FROM:\nPfizer AND University of Michigan and CDC\nIsmael R. Ortega -Sanchez, PhD\nNCIRD/CDC\nACIP Meeting, September 22, 2023\n1Disclaimer : The findings and conclusions in this report are those of the authors and do not necessarily represent the views of \nthe Centers for Disease Control and Prevention. \nNational Center for Immunization & Respiratory Diseases\nConflict of interest\n•Pfizer model : Amy Law et al., [complete authors list and affiliations, upon \nrequest ]\n•Pfizer manufactures RSVpreF vaccine\n•Policy Analysis Inc. (Boston, MA, US) was funded by Pfizer\n•UM-CDC model : David W Hutton et al. from University of Michigan,        \nIsmael R Ortega -Sanchez et al. from CDC [complete authors list and affiliations, \nupon request ]\n•All authors: No conflicts of interest\n2\nEconomic analysis\nPolicy question: Should Pfizer RSVpreF vaccine be recommended for pregnant mothers to be given \nduring 32 through 36 weeks gestation to prevent RSV lower respiratory tract infection in infants?\nQuestion : Is vaccinating pregnant mothers prior to birth to protect infants against RSV disease cost-\neffective ?\nComparator Intervention\nBase -case scenario: What is the incremental cost-effectiveness of vaccinating pregnant mothers 32 -36wGA and \n≥2 weeks prior to birth with RSVPreF vaccine relative to “No vaccination”?\n3Unvaccinated \nMothers +\nStandard of care (SoC)\nfor InfantsVaccination of \npregnant mothers \nprior to birth\nStandard of Care (SoC) = Palivizumab only for infants eligible as per AAP recommendations, and no immunization for all other pr e-term and full term infants\nFocus on key features for model comparison\n•Modeling approach\n•Targeted population(s)\n•Perspective (healthcare vs. societal)\n•Intervention strategies and comparators\n•Inputs for RSV disease burden, vaccine efficacy, and costs\n•Incidence of RSV disease, rates of outcomes \n•Direct and indirect costs of RSV disease\n•Intervention: efficacy, duration of protection, safety and program costs\n•Assumptions\n•Strong, influential assumptions\n4\n5Modeling design and assumptions\nPfizer UM-CDC\nStatic analytical decision -making models ✔ ✔\nSensitivity analyses (and probabilistic simulation) ✔(✔) ✔\nHypothetical population: All pregnant mothers, all year round ✔ ✔\nTime Frame: First year after birth ✔ ✔\nAnalytic Horizon: One year (for temporary disability) and Life \nExpectancy (for premature infant mortality)✔\n✔✔\n✔\nDiscount rate: 3% ✔ ✔\nYear of economic outcomes measured: 2022 ✔ ✔\nSocietal perspective (and healthcare perspective) ✔(✔) ✔(✔)\n6Inputs and main outcomes\nPrevention of:\n•RSV LRTI  ED/OC visits\n•RSV LRTI hospitalizations\n•RSV-associated deaths\nQALYs saved\n$/QALY saved\nNumber needed to\nvaccinate (NNV) to avert an:\n•RSV LRTI hospitalization\n•RSV-associated deathPfizer UM-CDC\n✔ ✔\n✔ ✔\n✔ ✔\n✔ ✔\n✔ ✔\n✔ ✔\n✔ ✔\nHCRU = health care resource use, ED= Emergency department,  OC= outpatient clinic, LRTI= Lower respiratory tract infection, \nQALY= quality -adjusted life year\n$11 $33 $68 $311 \n$13 $104 \n $- $50 $100 $150 $200 $250 $300 $350\nOutpatient ED Inpatient ICU Inpatient\nDayICU DayCost per Event Averted ( thousands )UM-CDC: Base case estimates for maternal vaccination, \nVaccination Window (VW) 32 -36wGA, vaccine cost $295/dose\n7Cost per type of health outcome prevented (in thousands ) Summary outcomes Base -Case\n$/QALY gained $400,304\n$/RSV -associated ED/OC visit \naverted $32,652 / $11,337  \n$/RSV -associated \nLRTI hospitalization averted$68,423\n$/RSV -assoc. death averted>$71.5Million\nNNV to avert an RSV -associated \nED/ OC patient115 /  40 \nNNV to avert an RSV -associated \nLRTI hospitalization242\nNNV to avert an RSV -associated \ndeath241,989\nAssuming 50% uptake in vaccinated group\nVW = vaccination window\nwGA = weeks gestational age\nLRTI= lower respiratory tract infection\nOC = office clinic for outpatient care\nED = emergency department\nNNV = Number needed to vaccinate\nPfizer model : Base case estimates for maternal vaccination, \nVW 32 -36wGA, vaccine cost $295/dose & PSA\n8Summary outcomes Base -Case\n$/QALY gained $84,690\n$/RSV -associated ED/OC visit \naverted$6,145/ $2,101\n$/RSV -associated LRTI  \nhospitalization averted$14,932\n$/RSV -associated death averted>$7.7Million\nNNV to avert an RSV -associated \nED/OC patient66 / 22\nNNV to avert an RSV -associated \nLRTI hospitalization159\nNNV to avert an RSV -associated  \ndeath82,243\nProbabilistic sensitivity analysis (PSA)87.1%\n65.1%\n34.7%\nDifference in total QALYsDifference in total costs ( in millions )\nBase -case Assuming 54.9% uptake in vaccinated group and 93.2% born ≥2 weeks after adm.\nVW = vaccination window\nwGA = weeks gestational age\nLRTI= lower respiratory tract infection\nOC = office clinic\nED = emergency department\nNNV = Number needed to vaccinate\nWTP = Willingness to pay\nPfizer and UM-CDC models comparison: base -case\nselected outcome ratios for maternal vaccination\n9UM-CDC model\nPrice per dose $295\nVW=32 -36wGA\nYear -round \nadministrationPfizer model\nPrice per dose $295\nVW=32 -36wGA\nYear -round\nadministration\n$ / QALY gained $400,304 $84,690\n$ / RSV LRTI hospitalization averted $68,423 $14,932\n$ / Death averted among RSV LRTI hospitalized infants >$71.5Million >$7.7Million\nNNV to prevent a\nRSV LRTI associated hospitalization 242 159\nDeath among RSV LRTI hospitalized infants 241,989 82,243\nAssuming 50% (UM -CDC) and 54.9% (Pfizer) uptake in vaccinated group and 100% (UM -CDC) to 93.2% (Pfizer) born ≥2 weeks after administration.\nVW = Vaccination window\nLRTI= lower respiratory tract infection\nNNV = Number needed to vaccinate\nNote: Both models vaccination window = 32 -36wGA only ( wGA = weeks gestational age)\n$0 $100 $200 $300 $400 $500 $600 $700 $800\nProbability of Prematurity\nRSV QALYS Lost\nRSVpreF vaccine cost/dose\nDisease-specific inpatient costs (per inpatient case)\nVaccination Efficacy, Hospitalized RSV LRTI through 180 days\nRSV-related QALYs lost Outpatient Child\nVaccination Efficacy, RSV MA-LRTI through 180 days\nProportion of RSV infections with an LRTI diagnosis…\nRSV-related QALYs lost Outpatient Caregiver\nRSV-related QALYs lost ED  ChildIncremental Cost -Effectiveness Ratio ( in thousands )\nLow\nHighUM-CDC model : One-way Sensitivity Analyses \nBase case: $ 400,304/ QALY saved, vaccine price $ 295/dose\n10MA= Medically -attended\nLRTI= Lower respiratory tract infection\nQALY= Quality adjusted life year$1.3 \nMillion\nBase -case $400,304\nPfizer model : One-way Sensitivity Analyses \nBase case: $84, 690/QALY saved, Vaccine cost $295/dose\n11CFR= Case fatality ratio\nDoP = Duration of protection\nVE= Vaccine efficacy\nPT = Preterm\nFT = Full termRSV-H = RSV -associated hospitalization\nRSV-ED = RSV -associated emergency department care\nRSV-OC = RSV -associated outpatient care15) VE lower bound\n14) RSV-H medical care cost lower bound\n13) US healthcare system perspective\n12) DoP = 6 months\n11) RSV-H CFR lower bound (overall = 0.1%)\n10) Vaccine uptake 32 -36 wGA (uniform)\n9) Disutilities form Glasser (RSV -H) and \nReigner (RSV -ED, RSV -OC)\n8) Uptake = 100%\n7)Base case\n6) VE for late PT = for FT\n5) Palivizumab scenario\n4) DoP = 12 months\n3) RSV-H CFR upper bound (overall=0.53%)\n2) RSV-H medical care cost upper bound\n1) VE upper bound\nBase -case $84,690\nSensitivity / Scenario AnalysisCost per QALY\nPfizer and UM-CDC models comparison: \nSelected influential inputs \n12•RSV-hospitalization risk and RSV seasonality\n•Vaccine efficacy\n•Duration of protection and waning\n•RSV Case fatality rate\n•Medical cost of RSV hospitalization, ED and Outpatient care\n•Vaccine associated adverse events\n•Quality of life lost by patients and caregivers\nPfizer and UM-CDC: comparison of base -case risk of \nRSV-related hospitalization by age and RSV Seasonality \n13Risk of RSV Hospitalization : Pfizer and UM-CDC: Based on laboratory -confirmed RSV-associated hospitalization by age in months from New Vaccine Surveillance \nNetwork (NVSN) data for children under 2 years of age (December 2016 to September 2020). Risk estimates are based only on RSV cases that manifest as LRTI.\nRSV Seasonality: Pfizer :based on Midgley et al. J Infect Dis 2017. (data based in NRVSS) https://pubmed.ncbi.nlm.nih.gov/28859428/#full -view -affiliation -1\nUM-CDC: based on National Respiratory and Enteric Virus Surveillance System (NREVSS) (2015 -2019)0%5%10%15%20%25%30%\nApr May Jun Jul Aug Sep Oct Nov Dec Jan Feb MarFraction of Annual Infections Pfizer\nUM-CDC\n00.0050.010.0150.020.0250.030.035\n0 1 2 3 4 5 6 7 8 9 10 11Risk of RSV LRTI hospitalization\nAge (in months)\nPfizer and UM-CDC:Differences in initial vaccine \nefficacy\n14NOTE: None of Pfizer Phase 3 (i.e., MATISSE) endpoint definitions overlapped ideally with the case definition used for the US burden data.\na. CDC: Average between efficacy for full term and preterm reported from Phase 3 were used. VE for RSV -LRTI hospitalization is an average over months 0-6 reported \nin Phase 3 trial , and RSV -positive MA -LRTI for VE against RSV -LRTI in the ED and outpatient. Kampmann et al New England Journal of Medicine . 2023 Apr\nb. Pfizer: Efficacy against severe RSV -positive MA -LRTI was used as a proxy for VE against RSV -LRTI requiring hospitalization, and efficacy against RSV -positive MA -LRTI \nwas used as a proxy for VE against RSV -LRTI treated in the ED. Pfizer: Kampmann et al New England Journal of Medicine . 2023 Apr\nc. VE for late preterm infants was assumed to be 83.3% of corresponding values for full term infants. VE for URTI was assumed equal to VE for MA LRTI in ED care\nd. Based on overall respiratory tract efficacy from phase 3 trial ( Kampmann et al New England Journal of Medicine . 2023 Apr )UM-CDCPfizer\nFull Term Late Preterm\nInitial vaccine efficacy against\nRSV LRTI hospitalization (%)Month 0 = 81.0\nAverage Month 0-6 = 56.8 a88.1\nSevere MA\nRSV-LTRIb73.4\nSevere MA\nRSV-LRTI b, c\nInitial vaccine efficacy against\nMedically attended RSV associated LRTI for ED \nand Outpatient care (%)Month 0 = 73.0\nAverage Month 0 -6 = 51.3 a47.6b39.7 c\nFor Scenario Analysis only : Initial efficacy \nagainst RSV URTI treated in Outpatient care (%)37.9 d47.6b39.7 c\n0%10%20%30%40%50%60%70%80%90%100%\n0 3 6 9 12Efficacy\nMonth\nAgainst medically-attended RSV-associated LRTI\nAgainst hospitalizationaverage 6 -month efficacy = \nefficacy against hospitalization \nor medically -attended RSV -\nassociated LRTI\nZero \nefficacy\nThe pink -shaded areas denote a higher level of uncertainty of the waning assumption beyond available phase 3 data\nUM-CDC: Average between efficacy for full term and preterm were used for DoP for RSV -LRTI hospitalization over months 0 -6 and RSV -positive MA -LRTI for DoP\nagainst RSV -LRTI in the ED and outpatient also over months 0 -6. Both r eported in Phase 3 trial , Kampmann et al New England Journal of Medicine . 2023 AprPfizer and UM-CDC: Assumption on duration of \nprotection ( DoP)\n15Pfizer UM-CDC\nVE against ED or OC             VE against hospitalization4 trial \nendpoints\n81.0\n73.0\n16UM-CDC Pfizer\nCase fatality rate (CFR) among RSV -\nhospitalized infants <12 months of age0.10%\n(0.04% -0.20%)a0.10% (full term)\n0.80% (all preterm) b\nMedical costs per RSV hospitalization$11,487\n($4,804 -$86,646)cAverage: $20,483 d\n$13,171 –$33,876 (full term)\n$19, 415 –$51,343 (late preterm)\nMedical costs per RSV ED visit$563\n($544 -$581)cAverage: $1,840 d\n$1,620 –$2,520 (full term)\n$1,787 –$2,779 (late preterm)\nMedical costs per RSV outpatient visit$82\n($46 -$118)cAverage: $348 d\n$292 –$730 (full term)\n$328 –$823 (late preterm)\na. RSV mortality per hospitalization: 0.10% (range 0.04 -0.20%) in 0 -5months, 0.10% (range 0.04 -0.20%) in 6 -11months.\nb. Case fatality due to RSV -Hospital in full term infants per 100 cases = 0.1   (based on Li et al CEA -RSV in children 2022).  I n pre -term infants CFR per 100= 0.8 (assumes 16.3% of all RSV -Hosp \nare among preterm) \nc. Adapted from Bowser et al., J Infect Dis . 2022 Aug 15; 226(Suppl 2): S225 –S235 (A systematic review using studies from 2014 -2021.  Cost updated to 2022 using the GPD de flator)\nd. Source: Pfizer data on file.  Costs in the base -case varied by age and term at birth. Weighted average cost among full and late preterm infants in commercially insured and Medicaid \npopulationsPfizer and UM-CDC models comparison: \nDifferences in key inputs\nPfizer and UM-CDC: Vaccine -associated adverse \nevents \n17UM-CDC Pfizer Source\nRate of injection site reaction0.41\n(0.38 –0.44)0.41\n(0.38 –0.44}Pfizer Phase III Trial\nProbability of healthcare visit, given \ninjection site reaction0.02\n(0.015 –0.025 )0.02\n(0.015 –0.025 )Curran, 2020\nCost of outpatient visit$367.76\n(23.15 –1,758)$367.76\n(23.15 –1,758)(Deluca, 2023) also in Pfizer CEA \ntechnical report (August 2023)\nRecipient time, physician office for \ninjection site reaction (hours)2\n(1 –3)n/r Assumption\nHypothetical serious adverse event0.000001\n(0 -0.0002)n/rBase: Prosser, 2006\nHigh: 95% CI Phase 3 data for \nRSV adult vaccines\nPotential risk increase of prematurity0.0%\n(0 –2%)n/rPfizer Phase III Trial\nKampmann et al New England \nJournal of Medicine . 2023 Apr\nNote: Values in bold are used for the base -case scenario. Range values in parenthesis for sensitivity analyses\nn/r = not reported\nPfizer and UM-CDC: Quality of life lost ( in days ) \nby RSV LRTI outcome for patients & caregivers\n18UM-CDC* Pfizer**\nOutpatient: Child3.1\n(1.8 -16.6)2.22\nOutpatient: Caregiver1.5\n(0 -9.1)1.5\nED: Child4.9\n(2.9 –16.6)2.22\nED: Caregiver2.5\n(0 -9.1)2.5\nHospitalized: Child6.2\n(3.7 –26.5)5.7\nHospitalized: Caregiver2.4\n(0 –13.6)2.4\nScenario Analysis : Vaccine -related increased \nrisk of prematurity ***11\n(0 –438)n/r\n* Base case values are from EGlasser et al 2022, lower values are based in Regnier et al 2013, higher values are based in JIVE (unpublished data)\n**Patient values are base in Roy 2013, Caregiver values are based on Hutton. Economic Analysis of Nirsevimab in Pediatric Populations. ACIP; February 23, 2023.\nNote: Values in bold are used for the base -case scenario. Range values in parenthesis for sensitivity analyses\n*** Sources: Werner, et al 2015. Petrini et al, 2008, Hirvonen et al, 2014, Crump et al, 2021, Darcy -Mahoney et al, 2016, Carroll et al, 2009, Payakachat et al, 2014\nn/r = not reported\n19UM-CDC\nUM-CDC model Base -case$400,304\nACost of RSV -LRTI hospitalization: $20,000 or $50,000 (i.e., 85% to 450% increase, base -case \ncost= $11,487)$350,500 -$174,987\nBUM-CDC model with same VE duration of protection as Pfizer : 6 months slowly, linearly \ndeclining efficacy and declining faster after month 6 reaching 0% at month 9$286,769\nCCFR among RSV LRTI hospitalization: 1% (base -case = 0.1%)$122,539\nDCombining A and B vs. Combining A, B and C$233,736 -$52,108\nEIncrease in the risk of prematurity in one-or two -percent points (base -case risk of prematurity \nafter vaccination = 0% increase )$874,609 -$1.3 Million\nFVaccine administration timing: September -January vs. February -July (base -case, year -round) <$200,000 -$Millions\nGVaccine cost = $50/dose or $500/dose (base -case vaccine cost = $295/dose) $65,304 -$680,609\nHVE for URTI = 37.9% (Base -case = 0% VE against URTI) $279,490Pfizer and UM-CDC models comparison: \n$/QALY for selected scenarios in UM-CDC model\n20Pfizer\nPfizer model base -case $84,690\nVE for late preterm infants assumed same as for full term infants a$73,404\nVaccine Efficacy :  80% or 120% of base case values $155,834  -$43,813\nTrial -based VE over 6 months, then 0% VEor linear waning to 0% VE at 12 months$111,473  -$61,925\nOverall CFR among RSV hospitalized:  0.1% or 0.53% b$102,431  -$52,000\nCosts of RSV -Hospitalization 80% or 120% of base -case)$118,625  -$50,755\nVaccination window: 32 -36 wGA only ( uniform: 20% in each week ) c$91,036\nMaternal vaccine and palivizumab in <1y infants vs.palivizumab only for prevention of RSV$66,796\na.Base -case assumes for late pre -term a VE =83%  of the VE for full term (VE = Vaccine efficacy)\nb.CFR among RSV hospitalized:  0.1% (RR of RSV -H death = 1 for full term and preterm infants). For CFR 0.53% (using CFR values fro m full term = 0.3% and preterm = 1.7%)  \nc.wGA = weeks gestational age Pfizer and UM-CDC models comparison: \n$/QALY for selected scenarios in Pfizer model  (I)\n21Pfizer\nAPfizer model with selected UM-CDC Inputs $343,000\nBPfizer model with selected UM-CDC Inputs except for Pfizer initial VE \nassumptions$265,000\nCPfizer model with selected UM-CDC Inputs except for Pfizer initial VE \nassumptions and Pfizer DoP $173,000\nDPfizer model with selected UM-CDC Inputs except for Pfizer initial VE \nassumptions, Pfizer DoP and Pfizer Medical costs$83,000\nEPfizer model with selected UM-CDC Inputs except for Pfizer initial VE \nassumptions, Pfizer DoP ,  Pfizer Medical costs and Palivizumab use$67,000\nDoP = Duration of protection\nVE = vaccine efficacyPfizer and UM-CDC models comparison: \n$/QALY for selected scenarios in Pfizer model  (II)\nLimitations\n22•Factors not considered that may result in overestimating the ICER \n(underestimating the cost -effectiveness) of maternal vaccination\n•In base -case: both models assumed \n•No protection against URTI\n•No benefits of vaccination for vaccinated pregnant women\n•No out -of-pocket cost accrued by caregivers during infants RSV illness\n•Neither model included RSV -related costs incurred after discharge from an \nRSV-associated hospitalization or emergency department visit:\n•Productivity losses incurred by caregivers after discharge\n•Both models assumed no indirect effects of vaccination (i.e., no protection \nagainst RSV transmission)\nConclusion\n23•Differences in key inputs among Pfizer and UM-CDC models explain differences in results:\n•Initial vaccine efficacy and assumptions about protection waning\n•Medical costs\n•Quality of life associated with RSV LRTI outcomes for patient and caregivers\n•Vaccine related adverse events\n•In addition, the UM-CDC also identified two important factors that could drive the results\n•Hypothetically severe vaccine -associated adverse events\n•Timing of vaccination to RSV season\n•Base -case in both models:\n•Maternal vaccination would significantly reduce RSV disease burden and costs in infants\n•Data from clinical trials used in both models support the reduction in RSV disease and \nassociated costs\n•Economic value of vaccinating pregnant people to protect infants could increase costs\n•Reasonable vaccine price and duration of protection combined with careful design of \nseasonal interventions would determine the cost-effectiveness value of routine \nvaccination of pregnant people during the 32 -36wGA\nAcknowledgements \nFrom NCIRD/CDC\n•Jefferson Jones\n•Mila M. Prill\n•Katherine E. Fleming -Dutra\n•Jamison Pike\n•Andrew Leidner\n•Meredith McMorrow\nAlso:\n•Maternal/Pediatric RSV working group members\n24\n\nEnd of Summary", "summary": "Economics of Preventing Respiratory Syncytial  Virus Disease among US Infants by Maternal  Vaccination Prior to Birth A SUMMARY REPORT COMPARING MODELS FROM: Pfizer AND University of Michigan and CDC Ismael R. Ortega -Sanchez, PhD NCIRD/CDC ACIP Meeting, September 22, 2023 1Disclaimer : The findings and conclusions in this report are those of the authors and do not necessarily represent the views of  the Centers for Disease Control and Prevention.  National Center for Immunization &…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-september-22-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-09-22/05-Mat-Peds-Ortega-Sanchez-508.pdf", "doc_date": "2023-09-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 25}
{"title": "06 Mat Peds Fleming Dutra 508", "content": "1\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nEvidence to Recommendations Framework Updates\nPfizer Maternal RSVpreF Vaccine\nACIP General Meeting\nSeptember 22, 2023Katherine E. Fleming -Dutra, MD\nCo-lead, Respiratory Syncytial Virus Vaccines –Pediatric/Maternal Work Group\nCoronavirus and Other Respiratory Viruses Division\nNational Center for Immunization and Respiratory Diseases\n2▪Should Pfizer RSVpreF vaccine be recommended for pregnant people to be given \nduring 32 through 36 weeks gestation to prevent RSV lower respiratory tract infection \nin infants?Policy question\nRSVpreF is a bivalent recombinant stabilized prefusion F protein subunit vaccine.\nKey points that have been updated since the June ACIP presentation are highlighted on the slides. \n3▪On August 21, 2023, FDA approved Pfizer RSVpreF vaccine for use in pregnant people \nas a single dose to be given at 32 through 36 weeks gestation\n▪In the phase 2b and 3 trials, vaccination was given during 24 through 36 weeks \ngestation \n▪Throughout the presentation, these will be denoted as\n•Approved dosing interval (32 –36 weeks gestation)\n•Trial dosing interval (24 –36 weeks gestation)FDA approval for RSVpreF vaccine\nFDA Approves First Vaccine for Pregnant Individuals to Prevent RSV in Infants | FDA\nVaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Briefing Document -FDA\nSame Pfizer RSV vaccine, formulation and dose approved for use in adults ages 60 years and older\n4Population Pregnant people\nIntervention Pfizer RSVpreF vaccine given at 32–36 weeks gestation\nComparison No vaccine\nOutcomes▪Medically attended RSV -associated lower respiratory tract infection in infants\n▪Hospitalization for RSV -associated lower respiratory tract infection in infants\n▪Intensive care unit (ICU) admission from RSV hospitalization in infants\n▪Mechanical ventilation from RSV hospitalization in infants\n▪RSV -associated death in infants\n▪All-cause hospitalization for lower respiratory tract infection in infants\n▪All-cause medically attended lower respiratory tract infection in infants\n▪Serious adverse events in pregnant people\n▪Reactogenicity (grade 3+) in pregnant people\n▪Serious adverse events in infants\n▪Preterm birth (<37 weeks gestation)Evidence to Recommendations ( EtR ) framework\nPICO question\n5Evidence to Recommendations ( EtR ) framework\nACIP Evidence to Recommendations Framework (cdc.gov)EtR Domain Question(s)\nPublic Health Problem ▪Is the problem of public health importance?\nBenefits and Harms ▪How substantial are the desirable anticipated effects?\n▪How substantial are the undesirable anticipated effects?\n▪Do the desirable effects outweigh the undesirable effects?\nValues ▪Does the target population feel the desirable effects are large relative \nto the undesirable effects?\n▪Is there important uncertainty about, or variability in, how much \npeople value the main outcomes?\nAcceptability ▪Is the intervention acceptable to key stakeholders?\nFeasibility ▪Is the intervention feasible to implement?\nResource Use ▪Is the intervention a reasonable and efficient allocation of resources?\nEquity ▪What would be the impact of the intervention on health equity?\n6\nEtR Domain: Public Health Problem\nIs the problem of public health importance?\n7▪Most (68%) infants are infected in the first year of life and \nnearly all (97%) by age 2 years2\n▪2–3% of young infants will be hospitalized for RSV3,4,5\n▪RSV is a common cause of lower respiratory tract infection \nin infants \n▪Highest RSV hospitalization rates occur in first months of \nlife and risk declines with increasing age in early \nchildhood3,5\n▪79% of children hospitalized with RSV aged <2 years had no \nunderlying medical conditions3RSV is the leading cause of hospitalization in U.S. \ninfants1\n1Suh et al. JID 2022 ; 2Glezen et al, Arch Dis Child, 1986 ; 3Hall et al, Pediatrics, 2013 ; 4Langley & Anderson, PIDJ, 2011 ; 5CDC NVSN data\nImage: Goncalves et al. Critical Care \nResearch and Practice 2012\n8▪Is RSV among infants of public health importance? Public Health Problem: Work Group interpretation\nNoProbably \nNoProbably \nYesYes VariesDon’t \nknow\n9\nEtR Domain: Benefits and Harms\nHow substantial are the desirable anticipated effects?\nHow substantial are the undesirable anticipated effects?\nDo the desirable effects outweigh the undesirable \neffects?\n10GRADE outcomes, importance, and data sources: Pfizer \nmaternal RSVpreF vaccine\nRCT = Randomized controlled trial; ICU= intensive care unit\n1 Three options: Critical; Important but not critical; Not important for decision making\n2 Among phase 2b trial participants, only those who received the vaccine formulation of the phase 3 trial or placebo were inc ludedOutcome Importance1 Data sources\nBenefits\nMedically attended RSV -associated lower respiratory tract infection in infants Critical Phase 3 RCT\nHospitalization for RSV -associated lower respiratory tract infection in infants Critical Phase 3 RCT\nICU admission from RSV hospitalization in infants Important Phase 3 RCT\nMechanical ventilation from RSV hospitalization in infants Important Phase 3 RCT\nRSV -associated death in infants Important Phase 3 and phase 2b2RCT\nAll-cause medically attended lower respiratory tract infection in infants Important Phase 3 RCT\nAll-cause hospitalization for lower respiratory tract infection in infants Important Phase 3 RCT\nHarms\nSerious adverse events in pregnant people Critical Phase 3 and phase 2b2RCT\nReactogenicity (grade 3+) in pregnant people Important Phase 3 and phase 2b2RCT\nSerious adverse events in infants Critical Phase 3 and phase 2b2RCT\nPreterm birth (<37 weeks gestation) Critical Phase 3 and phase 2b2RCT\n11Data available for GRADE and Benefits and Harms\nTrial phase Dosing interval Number of Participants* Decision regarding use in GRADE\nPhase 2b trial1Trial dosing \ninterval (24 –36 \nweeks gestation)Vaccine (received phase 3 dose \nand formulation): 115\nPlacebo: 117Yes. Data for GRADE were limited to participants \nwho received placebo or phase 3 vaccine \nformulation and only included for safety \noutcomes. Study was not designed to assess \nefficacy.\nPhase 2b trial1Approved dosing \ninterval (32 –36 \nweeks gestation)Vaccine (received phase 3 dose \nand formulation): 45\nPlacebo: 44No. Safety data are further limited by small \nsample size. Presented as supplemental data.\nPhase 3 trial published \nanalyses1,2,3Trial dosing \ninterval (24 –36 \nweeks gestation)Efficacy set / Safety set\nVaccine: 3495 / 3682\nPlacebo: 3480 / 3675Yes. Trial was designed and powered using a 24 –\n36 weeks dosing interval.\nPhase 3 trial, post -hoc \nanalysis1Approved dosing \ninterval (32 –36 \nweeks gestation)Efficacy set / Safety set\nVaccine: 1572 / 1653\nPlacebo: 1539 / 1632No. Trial was not powered for this interval for \nefficacy, and safety data would be limited in \npower to detect harms. Presented as \nsupplemental data.\n*For phase 2b trial and phase 3 trial safety set, number of maternal participants are listed. For phase 3 trial efficacy set, number of infants participants are listed.\n1 Data provided by Pfizer\n2 Kampmann et al. Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants -PubMed (nih.gov)\n3 Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Briefing Document -FDA\n12Effect estimates and concerns in certainty of assessment, \nbenefits : Pfizer maternal RSVpreF vaccine\nRCT= randomized controlled trial; CI= confidence interval; ICU= intensive care unit \n1 Three options: Critical; Important but not critical; Not important for decision making\n2 Vaccine efficacy was calculated as 1 –(P/[1 –P]), where P is the number of cases in the RSVpreF group divided by the total number of cases. The confidence interval was adjusted using the Bonferroni \nprocedure and accounting for the primary endpoints results. Efficacy is from full phase 3 trial data, using trial dosing interval (24 –36 weeks gestation).\n3 Serious concern for imprecision due to the width of the confidence interval containing estimates for which different policy decisions might be considered\n4 Vaccine efficacy was calculated as 1 –(P/[1 –P]), where P is the number of cases in the RSVpreF group divided by the total number of cases. Efficacy is from full phase 3 trial data, using trial dosing interval \n(24–36 weeks gestation).\n5 Very serious concern for imprecision due to the width of the confidence interval containing estimates for which different p olicy decisions might be considered and fragility of the estimate\n6 Among phase 2b trial participants, only those who received the vaccine formulation of the phase 3 trial or placebo were inc ludedOutcome Importance1Data sources Manufacturer \ncalculated vaccine efficacyConcerns in certainty \nassessment\nBenefits\nMedically attended RSV -associated lower respiratory tract infection in \ninfants (0 –180 days)Critical Phase 3 RCT 51.3% (97.58% CI: 29.4, 66.8)2 None\nHospitalization for RSV -associated lower respiratory tract infection in \ninfants (0 –180 days)Critical Phase 3 RCT 56.8% (99.17% CI: 10.1, 80.7)2 Imprecision (serious)3\nICU admission from RSV hospitalization in infants (0 –180 days) Important Phase 3 RCT 42.9% (95% CI: -124.8, 87.7)4Imprecision (very \nserious)5\nMechanical ventilation from RSV hospitalization in infants (0 –180 days) Important Phase 3 RCT 100% (95% CI: -9.1, 100)4Imprecision (very \nserious)5\nRSV -associated death in infants Important Phase 3 and \nphase 2b6RCT1 RSV -associated death occurred in the placebo arm of the \nphase 3 trial that was recorded at day 120 after birth. No RSV -\nassociated deaths were recorded in the phase 2b trial.\nAll-cause medically attended lower respiratory tract infection in infants \n(0–180 days)Important Phase 3 RCT 2.5% (99.17% CI: -17.9, 19.4)2 Imprecision (serious)3\nAll-cause hospitalization for lower respiratory tract infection in infants   \n(0–180 days)Important Phase 3 RCT 28.9% (95% CI: -2.0, 50.8)4 Imprecision (serious)3\n13Effect estimates and concerns in certainty of assessment, \nharms : Pfizer maternal RSVpreF vaccine\nRCT = Randomized -controlled trial\n1 Three options: Critical; Important but not critical; Not important for decision making\n2 Pooled relative risk estimates were independently calculated using counts of events and participants in the phase 3 trial i nterim analysis, and phase 2b trial among those who received the \nphase 3 vaccine formulation or placebo.\n3 Serious concern for indirectness as 55% of the Phase 3 RCT and 62% of the Phase 2b RCT did not receive vaccine or placebo i n the approved dosing interval (32 –36 weeks gestation). In the \napproved dosing interval, there is less opportunity for serious adverse events, including preterm birth/delivery, compared to the trial dosing interval (24 –36 weeks gestation).\n4 Serious concern for imprecision due to the width of the confidence interval containing estimates for which different policy decisions might be considered\n5 Serious concern for indirectness as these data only include systemic reactions. When selecting the a priori harm outcomes, the Work Group defined reactogenicity as both local and systemic \nreactions.\n6 Very serious concern for imprecision due to the width of the confidence interval containing estimates for which different p olicy decisions might be considered and not meeting optimal \ninformation size requirementsOutcome Importance1 Data sources Relative Risk2 (95% \nconfidence interval)Concerns in certainty \nassessment\nHarms\nSerious adverse events in pregnant people Critical Phase 3 and \nphase 2b RCT1.06 (0.95, 1.17) Indirectness (serious)3and\nImprecision (serious)4\nReactogenicity (grade 3+) in pregnant people Important Phase 3 and \nphase 2b RCT0.97 (0.72, 1.31) Indirectness (serious)5\nSerious adverse events in infants Critical Phase 3 and \nphase 2b RCT1.01 (0.91, 1.11) Indirectness (serious)3 and \nImprecision (serious)4\nPreterm birth (<37 weeks gestation) Critical Phase 3 and \nphase 2b RCT1.20 (0.99, 1.46) Indirectness (serious)3 and \nImprecision (very serious)6\n14Summary of GRADE: Pfizer maternal RSVpreF vaccine\nOutcome Importance Design (# of \nstudies)Findings Evidence Type\nBenefits\nMedically attended RSV -associated lower respiratory \ninfection in infants Critical RCT (1) Pfizer RSVpreF maternal vaccine is effective in preventing medically \nattended RSV -associated lower respiratory infection in infants High\nHospitalization for RSV -associated lower respiratory \ntract infection in infants Critical RCT (1) Pfizer RSVpreF maternal vaccine may be effective in preventing \nhospitalization for RSV -associated lower respiratory tract infection in \ninfants Moderate\nICU admission from RSV hospitalization in infants Important RCT (1) Pfizer RSVpreF maternal vaccine may be effective in preventing ICU \nadmission for RSV hospitalization in infantsLow\nMechanical ventilation from RSV hospitalization in \ninfants Important RCT (1) Pfizer RSVpreF maternal vaccine may be effective in preventing \nmechanical ventilation for RSV hospitalization in infantsLow\nRSV -associated death in infants Important RCT (2) 1 event observed in a placebo recipient among both trials Not evaluated\nAll-cause medically attended lower respiratory tract \ninfection in infants Important RCT (1) Pfizer RSVpreF maternal vaccine is not effective in preventing all -\ncause medically attended lower respiratory tract infection in infants Moderate\nAll-cause hospitalization for lower respiratory tract \ninfection in infants Important RCT (1) Pfizer RSVpreF maternal vaccine may be effective in preventing all -\ncause hospitalization for lower respiratory tract infection in infantsModerate\nHarms\nSerious adverse events in pregnant people Critical RCT (2) SAEs in pregnant people were balanced between vaccine and placebo \ngroupsLow\nReactogenicity (grade 3+) in pregnant people Important RCT (2) Reactogenicity in pregnant people was balanced between vaccine and \nplacebo groupsModerate\nSerious adverse events in infants Critical RCT (2) SAEs in infants were balanced between vaccine and placebo groups Low\nPreterm birth (<37 weeks gestation) Critical RCT (2) Preterm births were unbalanced between vaccine and placebo groups Very low\nRCT = Randomized -controlled trial\n15Summary of GRADE: Pfizer maternal RSVpreF vaccine\nThe overall evidence type is driven by the lowest quality of evidence for critical outcomes, and here is driven by the eviden ce rating \nfor the critical harm of preterm birth being very low. Overall \nevidence type: \nVery Low\n\n16Effect estimates, benefits : Pfizer maternal RSVpreF vaccine \ncomparing trial vs approved dosing interval\nCI= confidence interval; ICU=Intensive care unit\n1 Vaccine efficacy was calculated as 1 –(P/[1 –P]), where P is the number of cases in the RSVpreF group divided by the total number of cases. Confidence intervals that are not 95% were adjusted using the Bonferroni \nprocedure and accounting for the primary endpoints results. \n2 Vaccine efficacy was calculated as 1 -(hP/[1-P]), where P is the number of cases in the RSVpreF group divided by the total number of cases and h is the ratio of number of participants at risk in the placebo group to \nthe number of participants at risk in the RSVpreF group.OutcomeTrial dosing interval\n(24–36 weeks gestation)Approved dosing interval \n(32–36 weeks gestation)\nManufacturer calculated  \nvaccine efficacy (CI)1Manufacturer calculated vaccine \nefficacy (95% CI)2\nBenefits\nMedically attended RSV -associated lower respiratory tract \ninfection in infants (0 –180 days)51.3% (97.58% CI: 29.4, 66.8) 57.3% (95% CI: 29.8, 74.7)\nHospitalization for RSV -associated lower respiratory tract \ninfection in infants (0 –180 days)56.8% (99.17% CI: 10.1, 80.7) 48.2% ( 95% CI: -22.9, 79.6)\nICU admission from RSV hospitalization in infants (0 –180 days)42.9% (95% CI: -124.8, 87.7) 1 event in the vaccine group  \n2 events in the placebo group \nMechanical ventilation from RSV hospitalization in infants (0 –\n180 days)100% (95% CI: -9.1, 100) 0 events in the vaccine group  \n2 events in the placebo group \nAll-cause medically attended lower respiratory tract infection in \ninfants (0 –180 days)2.5% (99.17%: -17.9, 19.4) 7.3% ( 95% CI: -15.7, 25.7)\nAll-cause hospitalization for lower respiratory tract infection in \ninfants (0 –180 days)28.9% (95% CI: -2.0, 50.8) 34.7% ( 95% CI: -18.8, 64.9)\n17▪As defined in the Pfizer trial, this outcome \nwas not included by the Work Group as an \na priori critical or important outcome for \nGRADE for vaccine policy decisions\n▪Severe medically -attended RSV -\nassociated LRTI* required at least 1 of the \nfollowing signs/ symptoms:\n–Fast breathing (respiratory rate ≥70 (<2 month of \nage [60 days]) or ≥60 (≥2 to 12 months of age) \nbreaths per minute\n–SpO2 measured in room air <93%\n–High -flow nasal cannula or mechanical \nventilation\n–ICU admission for >4 hours\n–Unresponsive/unconscious▪Included by the Work Group as an a priori\ncritical outcome for GRADE for vaccine \npolicy decisions\n▪Medically -attended RSV -associated LRTI* \nrequired at least 1 of the following \nsigns/symptoms:\n–Fast breathing: respiratory rate ≥60 (<2 months \nof age [60 days]) or ≥50 (≥2 to 12 months of age) \nbreaths per minute\n–SpO2 measured in room air <95%\n–Chest wall indrawingSevere medically attended RSV -associated lower \nrespiratory tract infection (LRTI), co -primary trial endpoint\n*Medically attended visit includes inpatient and outpatient encounters. Additionally, definition also required RT -PCR or nucleic acid amplification (NAAT) test positive for RSV. Blue text \ndenotes differences between the two definitions. SpO2= Peripheral capillary oxygen saturation\n1. Kampmann et al. Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants -PubMed (nih.gov)\n2. Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Briefing Document -FDA\n18Phase 3 trial vaccine efficacy against severe medically \nattended RSV -associated LRTI, co -primary trial endpoint\n1 Vaccine efficacy was calculated as 1−(P/[1−P]), where P is the number of cases of illness in the RSVpreF group divided by the total number of cases of illness. At 90 days, 99.5% \nconfidence intervals (CIs) were used (determined by the alpha -spending function and adjusted with the use of the Bonferroni proc edure), and at later intervals, 97.58% CIs were \nused (based on a two -sided alpha level of 0.0483 adjusted with the use of the Bonferroni procedure).\n2 Vaccine efficacy was calculated as 1 -(hP/[1-P]), where P is the number of cases in the RSVpreF group divided by the total number of cases and h is the ratio of number of \nparticipants at risk in the placebo group to the number of participants at risk in the RSVpreF group.\n1. Kampmann et al. Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants -PubMed (nih.gov)\n2.Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Briefing Document -FDATime period \nafter birthTrial dosing interval\n(24–36 weeks gestation)\nVaccine efficacy1 (99.5% or \n97.58% CI)Approved dosing interval \n(32–36 weeks gestation)\nVaccine efficacy2 \n(95% CI)\n0–90 days \nafter birth81.8% (40.6, 96.3) 91.1% (38.8, 99.8)\n0–180 days \nafter birth69.4% (44.3, 84.1) 76.5% (41.3, 92.1)Within 0 -180 days after birth\n•Among 81 infants with \nsevere medically attended \nRSV LRTI, 50 (62%) were \nhospitalized\n•Among 63 infants \nhospitalized with RSV, 50 \n(79%) had severe medically \nattended RSV LRTI\n19Effect estimates, harms : Pfizer maternal RSVpreF vaccine \ncomparing trial vs approved dosing interval\nCI= confidence interval\n1 Phase 3 and 2b trials\n2 Pooled relative risk estimates were independently calculated using counts of events and participants in the phase 3 trial i nterim analysis, and phase 2b trial among those who \nreceived the phase 3 vaccine formulationOutcomeTrial dosing interval1\n(24–36 weeks)Approved dosing interval1\n(32–36 weeks)\nRelative Risk2 (95% CI) Relative Risk2 (95% CI)\nHarms\nSerious adverse events in pregnant people 1.06 (0.95, 1.17) 1.02 (0.87, 1.20)\nReactogenicity (grade 3+) in pregnant people 0.97 (0.72, 1.31) 0.98 (0.62, 1.54)\nSerious adverse events in infants 1.01 (0.91, 1.11) 1.04 (0.90, 1.20)\nPreterm birth (<37 weeks gestation) 1.20 (0.99, 1.46) 1.15 (0.82, 1.61)\n20Effect estimates, harms : Pfizer maternal RSVpreF vaccine \ncomparing trial vs approved dosing interval\nCI= confidence interval\n1 Phase 3 and 2b trials\n2 Pooled relative risk estimates were independently calculated using counts of events and participants in the phase 3 trial i nterim analysis, and phase 2b trial among those who \nreceived the phase 3 vaccine formulationOutcomeTrial dosing interval1\n(24–36 weeks)Approved dosing interval1\n(32–36 weeks)\nRelative Risk2 (95% CI) Relative Risk2 (95% CI)\nHarms\nSerious adverse events in pregnant people 1.06 (0.95, 1.17) 1.02 (0.87, 1.20)\nReactogenicity (grade 3+) in pregnant people 0.97 (0.72, 1.31) 0.98 (0.62, 1.54)\nSerious adverse events in infants 1.01 (0.91, 1.11) 1.04 (0.90, 1.20)\nPreterm birth (<37 weeks gestation) 1.20 (0.99, 1.46) 1.15 (0.82, 1.61)\n21▪Trial of a similar GSK maternal RSV vaccine (stabilized prefusion F protein vaccine without an adjuvant) \nwas halted due to an imbalance of preterm births with higher numbers in the vaccine vs placebo group\n▪Imbalance of neonatal deaths was a consequence of preterm birth imbalance\n▪Imbalance in preterm births was seen in low and middle -income countries (RR: 1.57, 95% CI: 1.17, 2.10) \nbut not high -income countries (RR: 1.04, 95% CI: 0.68, 1.58)\n▪Imbalance was observed from April –December 2021, but not consistently after December 2021  \n▪Reason for the imbalance remains unclearGSK maternal RSV vaccine clinical trial and preterm birth\nStudy vaccine given at 24 0/7 to 34 0/7 weeks gestation\nVaccines and Related Biological Products Advisory Committee February 28 -March 1, 2023 Meeting Briefing Document -Sponsor GSK ( fda.gov)Outcome Vaccine group, n (%) \nN=3,496Placebo group, n (%)\nN=1,739Relative Risk (95% CI)\nPreterm birth (<37 weeks \ngestation)238 (6.81%) 86 (4.95%) 1.38 (1.08, 1.75)\nNeonatal death 13 (0.37%) 3 (0.17%) 2.16 (0.62, 7.55)\n22Preterm birth in Pfizer RSVpreF vaccine phase 3 trial data, \ncomparing trial vs approved dosing interval\nTrial dosing interval\n(24–36 weeks gestation)1Approved dosing interval \n(32–36 weeks gestation)1,2\nRSVpreF vaccine \ngroup\nN=3,568Placebo group\nN=3,558RSVpreF vaccine \ngroup\nN=1,628Placebo group\nN=1,604\nn % (95% CI) n % (95% CI) n % (95% CI) n % (95% CI)\nPreterm birth \n(<37 weeks \ngestation)202 5.7% \n(4.9%, 6.5%)169 4.7% \n(4.1%, 5.5%)68 4.2% \n(3.3%, 5.3%)59 3.7%\n(2.8%, 4.7%)\n1. Package Insert -ABRYSVO (STN 125768) (fda.gov)\n2. Pfizer response to ACIP , unpublished data, August 2023. In package insert, approved dosing interval reported as: 4.2% (68/ 1,631) in the RSVpreF group and 3.7% (59/1,610) in \nthe placebo group. \n23Low birth weight and neonatal jaundice outcomes in Pfizer \nRSVpreF vaccine phase 3 trial data, trial vs approved dosing \ninterval\nTrial dosing interval\n(24–36 weeks gestation)1,2Approved dosing interval \n(32–36 weeks gestation) 3\nRSVpreF vaccine \ngroup\nN=3,568Placebo group\nN=3,558RSVpreF vaccine \ngroup\nN=1,628Placebo group\nN=1,604\nn % (95% CI) n % (95% CI) n % (95% CI) n % (95% CI)\nLow birth \nweight \n(≤2500 g)181 5.1% \n(4.4%, 5.8%)155 4.4%\n(3.7%, 5.1%) 67 4.1% \n(3.2%, 5.2%)54 3.4% \n(2.5%, 4.4%)\nNeonatal \njaundice 257 7.2%\n(6.4%, 8.1%)240 6.7%\n(5.9%, 7.6%)102 6.3%\n(5.1%, 7.6%)107 6.7%\n(5.5, 8.0%)\n1.Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Presentation -Review of Efficacy and Safety of Respiratory Syncytial Virus Vaccine (ABRYSVO) (fda.gov)\n2.Package Insert -ABRYSVO (STN 125768) (fda.gov)\n3.Pfizer response to ACIP , unpublished data, August 2023\n24▪Rate of preterm birth by calendar month of birth\n▪Birth by week of gestational age\n▪Percent of births that were preterm by country\n▪Adverse pregnancy outcomesIn June, ACIP requested additional data regarding the \nPfizer maternal RSV vaccine\n25Preterm birth rate for vaccine and placebo recipients by \ncalendar time —Pfizer Phase 3 trial, trial dosing interval (24 –\n36 weeks gestation)\nGSK signal was present from \nApril –December 2021\nData source: Pfizer response to ACIP , unpublished data, July 2023\n26\nPreterm birth rate for vaccine and placebo recipients by \ncalendar time —Pfizer Phase 3 trial, approved dosing \ninterval (32 –36 weeks gestation)\nGSK signal was present from April –\nDecember 2021\nData source: Pfizer response to ACIP , unpublished data, September 2023\n27Number of births by gestational age: Pfizer phase 3 trial, \ntrial dosing interval (24 –36 weeks gestation)\n1 0 1 1 3 1 14 26 291253367641262\n738\n243\n20 1 0 1 0 1 2 3 1 4 2242933497551321\n680\n251\n272 1\n0200400600800100012001400\n≥27 to <28 weeks\n≥28 to <29 weeks\n≥29 to <30 weeks\n≥30 to <31 weeks\n≥31 to <32 weeks\n≥32 to <33 weeks\n≥33 to <34 weeks\n≥34 to <35 weeks\n≥35 to <36 weeks\n≥36 to <37 weeks\n≥37 to <38 weeks\n≥38 to <39 weeks\n≥39 to <40 weeks\n≥40 to <41 weeks\n≥41 to <42 weeks\n≥42 to <43 weeks\n≥43 to <44 weeks\n≥44 to <45 weeksNumber of Births\nGestational Age at BirthVaccine Placebo\nPreterm birth: <37 weeks gestation\nData source: Pfizer response to ACIP , unpublished data, July 2023\n28Number of births by gestational age, preterm births (<37 \nweeks gestation) only: Pfizer phase 3 trial, trial dosing \ninterval (24 –36 weeks gestation)\n1 0 1 1 3 1142629125\n1 0 1 2 3 14224293\n020406080100120\n≥27 to <28 weeks\n≥28 to <29 weeks\n≥29 to <30 weeks\n≥30 to <31 weeks\n≥31 to <32 weeks\n≥32 to <33 weeks\n≥33 to <34 weeks\n≥34 to <35 weeks\n≥35 to <36 weeks\n≥36 to <37 weeksNumber of Births\nGestational Age at BirthVaccine Placebo\nImbalance begins \nat 33 weeks\nPreterm birth: <37 weeks gestation\nData source: Pfizer response to ACIP , unpublished data, July 2023\n29Number of births by gestational age: Pfizer phase 3 trial, \napproved dosing interval (32 –36 weeks gestation)\nPreterm birth: <37 weeks gestation\nData source: Pfizer unpublished data, August 20230 2 6 1149148374567\n338\n120\n121 1 1 51735156334603\n325\n112\n140\n0100200300400500600\n≥32 to <33 weeks\n≥33 to <34 weeks\n≥34 to <35 weeks\n≥35 to <36 weeks\n≥36 to <37 weeks\n≥37 to <38 weeks\n≥38 to <39 weeks\n≥39 to <40 weeks\n≥40 to <41 weeks\n≥41 to <42 weeks\n≥42 to <43 weeks\n≥43 to <44 weeksNumber of Births\nGestational Age at BirthVaccine Placebo\n30Number of births by gestational age, preterm births (<37 \nweeks gestation) only:  Pfizer Phase 3 trial, approved \ndosing interval (32 –36 weeks gestation)\n0261149\n1 151735\n05101520253035404550\n≥32 to <33 weeks\n≥33 to <34 weeks\n≥34 to <35 weeks\n≥35 to <36 weeks\n≥36 to <37 weeksNumber of Births\nGestational Age at BirthVaccine Placebo\nPreterm birth: <37 weeks gestation\nData source: Pfizer unpublished data, August 2023\n31Number births and percent preterm by country –Pfizer phase 3 trial\nTrial dosing interval (24 –36 weeks gestation) Approved dosing interval (32 –36 weeks gestation)\nRSVpreF recipients\nN=3568Placebo recipients\nN=3558RSVpreF recipients\nN=1628Placebo recipients\nN=1604\nCountry No. births % preterm No. births % preterm No. births % preterm No. births % preterm\nArgentina 423 6.4% 416 4.1% 230 4.8% 230 4.3%\nAustralia 11 0.0% 13 7.7% 8 0.0% 8 12.5%\nBrazil 35 8.6% 37 2.7% 22 9.1% 23 4.3%\nCanada 27 0.0% 28 3.6% 20 0.0% 27 3.7%\nChile 86 8.1% 85 7.1% 47 6.4% 50 2.0%\nDenmark 30 3.3% 31 0.0% 21 4.8% 17 0.0%\nFinland 75 2.7% 73 1.4% 44 0.0% 40 2.5%\nGambia 78 2.6% 79 2.5% 32 3.1% 24 0.0%\nJapan 218 3.2% 216 6.0% 111 2.7% 94 2.1%\nKorea 7 0.0% 4 25.0% 6 0.0% 1 100.0%\nMexico 37 8.1% 37 5.4% 13 7.7% 13 0.0%\nNetherlands 97 3.1% 95 3.2% 43 2.3% 44 0.0%\nNew Zealand 49 4.1% 47 6.4% 29 3.4% 28 3.6%\nPhilippines 32 3.1% 34 5.9% 0 0.0% 1 0.0%\nSouth Africa 469 8.3% 471 4.0% 150 6.7% 127 2.4%\nSpain 117 3.4% 123 2.4% 73 2.7% 88 3.4%\nTaiwan 123 4.9% 125 5.6% 58 5.2% 57 3.5%\nUnited States 1654 5.7% 1644 5.3% 721 4.0% 732 4.4%\nData source: Pfizer response to ACIP, unpublished data, July and August 2023. Trial included 480 sites across 18 countries. N umb er of births is the total number of births regardless of gestational age. \nBlue indicates higher percent of preterm birth among RSVpreF vs. placebo in trial dosing interval, red in approved dosing int erval, and purple in both dosing intervals. Black indicates either balanced \npreterm birth rates or a higher percent of preterm births among placebo vs RSVpreF recipients. Caution should be used in inte rpreting rates based on small numbers; some differ by very small counts. \n32Number births and percent preterm by country –Pfizer phase 3 trial\nTrial dosing interval (24 –36 weeks gestation) Approved dosing interval (32 –36 weeks gestation)\nRSVpreF recipients\nN=3568Placebo recipients\nN=3558RSVpreF recipients\nN=1628Placebo recipients\nN=1604\nCountry No. births % preterm No. births % preterm No. births % preterm No. births % preterm\nArgentina 423 6.4% 416 4.1% 230 4.8% 230 4.3%\nAustralia 11 0.0% 13 7.7% 8 0.0% 8 12.5%\nBrazil 35 8.6% 37 2.7% 22 9.1% 23 4.3%\nCanada 27 0.0% 28 3.6% 20 0.0% 27 3.7%\nChile 86 8.1% 85 7.1% 47 6.4% 50 2.0%\nDenmark 30 3.3% 31 0.0% 21 4.8% 17 0.0%\nFinland 75 2.7% 73 1.4% 44 0.0% 40 2.5%\nGambia 78 2.6% 79 2.5% 32 3.1% 24 0.0%\nJapan 218 3.2% 216 6.0% 111 2.7% 94 2.1%\nKorea 7 0.0% 4 25.0% 6 0.0% 1 100.0%\nMexico 37 8.1% 37 5.4% 13 7.7% 13 0.0%\nNetherlands 97 3.1% 95 3.2% 43 2.3% 44 0.0%\nNew Zealand 49 4.1% 47 6.4% 29 3.4% 28 3.6%\nPhilippines 32 3.1% 34 5.9% 0 0.0% 1 0.0%\nSouth Africa 469 8.3% 471 4.0% 150 6.7% 127 2.4%\nSpain 117 3.4% 123 2.4% 73 2.7% 88 3.4%\nTaiwan 123 4.9% 125 5.6% 58 5.2% 57 3.5%\nUnited States 1654 5.7% 1644 5.3% 721 4.0% 732 4.4%\nData source: Pfizer response to ACIP, unpublished data, July and August 2023. Trial included 480 sites across 18 countries. N umb er of births is the total number of births regardless of gestational age. \nBlue indicates higher percent of preterm birth among RSVpreF vs. placebo in trial dosing interval, red in approved dosing int erval, and purple in both dosing intervals. Black indicates either balanced \npreterm birth rates or a higher percent of preterm births among placebo vs RSVpreF recipients. Caution should be used in inte rpreting rates based on small numbers; some differ by very small counts. \n33Select pregnancy -related serious adverse events at any \ntime following vaccination1,2: Pfizer phase 3 trial, trial \ndosing interval (24 –36 weeks gestation)\n1 Table 3 ABRYSVO package insert Package Insert -ABRYSVO (STN 125768) (fda.gov)\n2 Includes all SAEs from vaccination to 6 months post -delivery (up to approximately 10 months, depending on the gestational age at the time of vaccination). In the phase 3 RCT, \neclampsia occurred in 5 participants (3 in the RSVpreF group and 2 in the placebo group) and HELLP syndrome occurred in 5 participants (2 in the RSVpreF group and 3 in the \nplacebo group).\n3 There was one maternal death in the vaccine group due to postpartum hemorrhage that was not likely to be associated with va ccination.\n4 A total of 18 intrauterine deaths were reported for the index pregnancy: 10 intrauterine deaths in the vaccine group (0.3%) and 8 intrauterine deaths in the placebo group \n(0.2%). The intrauterine deaths represented various clinical conditions and presentations resulting in fetal demise without c lear evidence of a common pathophysiology.RSVpreF Vaccine \nN= 3,682Placebo\nN= 3,675\nSerious Adverse Reaction n (%) 95% CI n (%) 95% CI\nAll Maternal Serious Adverse Events (SAEs) 598 (16.2) (15.1, 17.5) 558 (15.2) (14.0, 16.4)\nPre-eclampsia 68 (1.8) (1.4, 2.3) 53 (1.4) (1.1, 1.9)\nGestational hypertension 41 (1.1) (0.8, 1.5) 38 (1.0) (0.7, 1.4)\nPremature rupture of membranes 15 (0.4) (0.2, 0.7) 16 (0.4) (0.2, 0.7)\nPreterm premature rupture of membranes 15 (0.4) (0.2, 0.7) 10 (0.3) (0.1, 0.5)\nHypertension 13 (0.4) (0.2, 0.6) 6 (0.2) (0.1, 0.4)\nMaternal death31 (<0.1) (0.0, 0.2) 0 (0.0, 0.1)\nFetal death410 (0.3) (0.1, 0.5) 8 (0.2) (0.1, 0.4)\n34▪Same Pfizer RSV vaccine, formulation and dose approved for use in adults ages 60 \nyears and older\n▪Within the trials for this product among adults ages 60 years and older, a potential\nsafety signal of inflammatory neurologic events was identified\n▪A total of 3 cases of interest were recorded among 20,255 investigational vaccine \nrecipients aged 60 years and older. No cases were observed among placebo \nrecipients.\n–1 case of Guillain -Barré Syndrome (GBS)\n–1 case of Miller Fisher syndrome (a GBS variant)\n–1 case of undifferentiated motor -sensory axonal polyneuropathy (with \nworsening of preexisting symptoms)Other considerations: Inflammatory neurologic events and \nPfizer RSVpreF Vaccine \nMelgar et al. Use of Respiratory Syncytial Virus Vaccines in Older Adults: Recommendations of the Advisory Committee on Immun ization Practices —United States, 2023 | \nMMWR (cdc.gov)\n35▪No Guillain -Barré syndrome (GBS) or other demyelinating events were \nreported in the phase 2b or 3 trials among pregnant people1\n▪Background rate of GBS in pregnant people is much lower than among \nolder adults2,3\n▪Incidence rate of GBS in pregnant people in the Vaccine Safety Datalink \nduring 2004 –2015 : 2.8 (95% CI 0.5 –9.3) per million person -years (based on \n2 cases)2Other considerations: Inflammatory neurologic events and \nPfizer RSVpreF Vaccine (cont.)\n1.Vaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Briefing Document -FDA\n2.Myers TR, McCarthy NL, Panagiotakopoulos L, Omer SB. Estimation of the Incidence of Guillain -Barré Syndrome During Pregnancy in the United States. Open Forum Infect Dis. \n2019 Mar 15;6(3):ofz071. doi: 10.1093/ ofid/ofz071. \n3.Sejvar JJ, Baughman AL, Wise M, Morgan O. Population Incidence of Guillain -Barré Syndrome: A Systematic Review and Meta -Analysis. Neuroepidemiology 2011;36:123 –133 \n36▪Efficacious vaccine that can prevent RSV lower respiratory tract \ninfection in young infants\n▪No consensus among Work Group regarding clinical importance \nof preterm birth imbalance observed in clinical trialsSummary of Benefits and Harms\n37▪Though not statistically significant, imbalance in preterm births was seen in the full \ntrial population\n▪Trial powered for efficacy outcomes and not designed or powered to detect 20% \nincrease in preterm birth\n▪There may have been less precise dating of gestational age in some sites and \ncountries in the trial, but there is no reason this should bias towards a preterm birth \nimbalance among vaccinated compared to placebo participants\n▪Preterm birth signal in the GSK maternal RSV vaccine trial (also a stabilized prefusion \nF protein vaccine) adds to concernWork Group members found the following points \nconcerning regarding preterm birth\n38▪When using the full trial dosing interval (24 –36 weeks gestation), most preterm births (60%) \nwere >30 days after vaccination, and no known biologic mechanism for vaccines to cause \npreterm birth, particularly >30 days after vaccination\n▪When assessed among those vaccinated during the approved interval (32 –36 weeks \ngestation), data on preterm birth were reassuring to the Work Group\n–Imbalance in preterm birth was still present but lessened\n–Most infants born preterm in the vaccine group (72%, 49/68) were born at 36 weeks\n–In the United States (largest contributing country in the trial), imbalance in preterm births \nreversed: \n•Trial dosing interval: 5.7% in vaccine vs. 5.3% in placebo recipients\n•Approved dosing interval: 4.0% in vaccine vs. 4.4% in placebo recipients \n▪Majority of the Work Group felt the approved dosing interval (32 –36 weeks gestation) reduces \nthe potential risk of preterm birth and the potential for complications from preterm birth, \nwhich is their major safety concernWork Group members found the following data reassuring \nregarding preterm birth imbalance\n39▪How substantial are the desirable anticipated effects?\n–How substantial are the anticipated effects for:\n•Medically attended RSV -associated lower respiratory infection in infants \n•Hospitalization for RSV -associated lower respiratory tract infection in infants \n•ICU admission from RSV hospitalization in infants \n•Mechanical ventilation from RSV hospitalization in infants \n•RSV -associated death in infants \n•All-cause hospitalization for lower respiratory tract infection in infants \n•All-cause medically attended lower respiratory tract infection in infants Benefits and Harms -Pfizer maternal RSVpreF vaccine, \ngiven as a single dose at 32–36 weeks gestation\nMinimal Small Moderate Large Varies Don’t know\nMinority Opinion Majority Opinion0\n40▪How substantial are the undesirable anticipated effects?\n–How substantial are the anticipated effects for:\n•Serious adverse events in pregnant people \n•Reactogenicity (3+ or higher) in pregnant people \n•Serious adverse events in infants \n•Preterm birth Benefits and Harms -Pfizer maternal RSVpreF vaccine, \ngiven as a single dose at 32–36 weeks gestation\nMinimal Small Moderate Large Varies Don’t know\nMajority Opinion\n41▪Do the desirable effects outweigh the undesirable effects?\n–What is the balance between the desirable effects relative to the \nundesirable effects?Benefits and Harms -Pfizer maternal RSVpreF vaccine, \ngiven as a single dose at 32–36 weeks gestation\nFavors intervention (Pfizer Maternal RSVpreF \nVaccine)\nFavors comparison (No intervention)\nFavors both\nFavors neither\nUnclear0\nMajority Opinion\n42\nEtR Domain: Values\nCriterion 1: Does the target population feel that the \ndesirable effects are large relative to undesirable effects? \nCriterion 2: Is there important uncertainty about, or \nvariability in, how much people value the main \noutcomes?\n43▪Values survey of pregnant and recently pregnant people conducted from December \n21, 2022 –January 2, 2023 by University of Iowa, RAND, and CDC1\n–68% of respondents had knowledge of RSV prior to taking survey\n–61% of respondents said they ‘definitely’ or ‘probably’ would get an RSV vaccine while pregnant\n–Among those who did not respond that they “definitely would” get an RSV vaccine while pregnant, safety \nconcerns, lack of RSV knowledge, and concerns about vaccination causing or intensifying RSV infection \nwere the top reasons for not wanting an RSV vaccine during pregnancy\n▪In the US, coverage for recommended vaccines among pregnant people has decreased \nduring the pandemic and varies by race and ethnicity2\n–Tdap vaccination coverage was 53.5% in 2020 –21 season and 45.8% in 2021 –22 season\n–Rates of Tdap coverage were higher in White, non -Hispanic women than among Black, non -Hispanic women \nduring the 2020 –21 and 2021 –22 seasonsSummary of values domain\n1 CDC and University of Iowa/RAND survey, unpublished\n2Flu, Tdap, and COVID -19 Vaccination Coverage Among Pregnant Women –United States, April 2022 | FluVaxView | Seasonal Influenza (Flu) | CDC\n44▪Criterion 1: Do pregnant people feel that the desirable effects \nare large relative to undesirable effects?Values\nNo Probably No Probably Yes Yes Varies Don’t know\nMajority Opinion\n45▪Criterion 2: Is there important uncertainty about, or variability in, \nhow much pregnant people value the main outcomes?Values\nImportant uncertainty or variability\nProbably important uncertainty or variability\nProbably not important uncertainty or variability\nNo important uncertainty or variability\nNo known undesirable outcomes\nMost common answers\n46\nEtR Domain: Acceptability\nIs the intervention acceptable to key stakeholders?\n47▪Obstetrician and midwife support of RSV vaccine, if it was routinely \nrecommended:\n–47% definitely\n–34% likely\n–14% not sure\n–4% unlikely\n–0.5% very unlikelyMaternity healthcare professionals survey —England, 2019\nWilcox CR, Calvert A, Metz J, et al. Attitudes of Pregnant Women and Healthcare Professionals Toward Clinical Trials and Routine Implementation of Antenatal Vacci nation Against \nRespiratory Syncytial Virus: A Multicenter Questionnaire Study. The Pediatric Infectious Disease Journal. 2019 Sept;38(9):944 -951. DOI: 10.1097/INF.0000000000002384\n48▪Is RSV prevention with Pfizer maternal RSVpreF vaccine \nacceptable to key stakeholders?Acceptability\nNo Probably No Probably Yes Yes Varies Don’t know\nMinority Opinion Majority Opinion\n49\nEtR Domain: Feasibility\nIs the intervention feasible to implement?\n50▪Storage and handling requirements\n–Supplied as single 0.5 mL dose, or as a 5 -pack or 10 -pack of single -dose kits \n–Reconstitution required: single dose vial of lyophilized powder, reconstitution \nsupplies included in kit \n–Product should be refrigerated (2 –8°C) in original container, protected from light \n–After reconstitution, the product should be administered within 4 hours, otherwise \ndiscarded\n▪Most pregnant patients receive Tdap vaccine in an obstetrician's or midwife’s office\n–Likely pregnant patients would also most often receive RSV vaccine at their prenatal \ncare provider’s officeStorage and handling\nPackage Insert -ABRYSVO (STN 125769/26) (fda.gov) \nFlu, Tdap, and COVID -19 Vaccination Coverage Among Pregnant Women –United States, April 2022 | FluVaxView | Seasonal Influenza (Flu) | CDC\n51▪Pregnant people may potentially be eligible to receive RSV, Tdap, COVID -19, and \ninfluenza vaccines at same visit\n▪Pfizer Phase 2b study in healthy non -pregnant women ages 18 –49 years on \nsimultaneous administration of Tdap and Pfizer RSVpreF found decreased immune \nresponse to pertussis components (i.e., non -inferiority criteria were not met)1\n▪Given lack of correlates of protection for pertussis, it is unclear how this might impact \nprotection against pertussis from maternal Tdap when simultaneously administered \nwith RSVpreF vaccineSimultaneous administration of RSV vaccine with other \nvaccines in pregnant people\n1 Peterson et al. Safety and Immunogenicity of a Respiratory Syncytial Virus Prefusion F Vaccine When Coadministered With a Tetanus, Diphtheria, and Acellular Pertussis \nVaccine. The Journal of Infectious Diseases. 2022 June 15; 225(12): 2077 –2086. doi: 10.1093/ infdis /jiab505\n52▪Tdap recommended every pregnancy, preferably during the early part of gestational \nweeks 27 through 361\n▪Tdap would be preferably given before 32 weeks (based on recommendation) and RSV \nvaccine would be given at or after 32 weeks\n▪In MarketScan data from 2018 –2021, about half of captured Tdap doses were given \nbefore 32 weeks gestation2RSV vaccine and Tdap dosing timing\n1 CDC, https://www.cdc.gov/vaccines/vpd/dtap -tdap -td/hcp/recommendations.html\n2 MarketScan data, 2018 -2021\n53▪Either RSV vaccination during pregnancy or nirsevimab administration for the infant \ncan be used to prevent RSV lower respiratory tract infection in infants\n▪Work Group felt both products are not needed for most infants\n▪Pregnant person and prenatal care provider will need to make the decision during \npregnancy regarding which RSV prevention product to use\n▪Many prenatal care providers may not have time to discuss options for RSV prevention \nwith their patients\n▪Prenatal care providers may not feel equipped to discuss nirsevimab, as this product \nwill be given to the infant after birthRSVpreF vaccine is one of two available preventive \nproducts for RSV in infants\n54▪Maximizes cost -effectiveness\n▪Maximizes benefits for infants \n▪Targets dosing to infants who will be in the first months of life during RSV season\n▪Another product (nirsevimab) is available for infants who are born out of season —for \nwhom maternal vaccine protection would have waned by RSV seasonWork Group unanimously supported use of a seasonal \ndosing strategy for maternal RSV vaccine\n55▪Work Group supported seasonal dosing during September through January in most \nof the continental US based on typical (pre -pandemic) RSV seasonality\n–Aligns with implementation of influenza vaccine and thus would simplify \nimplementation for prenatal care providers \n▪Work Group felt that jurisdictions in which RSV seasonality differs from most of the \ncontinental US should have flexibility regarding start and stop of administration of \nRSVpreF vaccine in pregnant people\n•Alaska\n•Tropical climates: parts of Florida, Puerto Rico, U.S. Virgin Islands, Hawaii, Guam, \nand U.S. -affiliated Pacific IslandsSeasonal dosing for RSVpreF vaccine\n56▪Is Pfizer Maternal RSVpreF vaccine feasible to implement among \npregnant people at 32 –36 weeks gestation ?Feasibility\nNo Probably No Probably Yes Yes Varies Don’t know\nMinority Opinion Majority Opinion\n57\nEtR Domain: Resource Use\nIs the intervention a reasonable and efficient allocation of \nresources?\n58Scenarios for cost -effectiveness by months of RSVpreF\nvaccine dosing during the calendar year\nICER: Incremental cost -effectiveness ratio\nQAL Y: Quality -Adjusted Life -Year\nCost -effectiveness model assumes typical RSV seasonality (based on pre -pandemic years) in most of the continental United States.$400,304 \n$363,344 \n$322,594 \n$282,498 \n$186,256 $167,280 $141,806 \n $- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000 $450,000\nBase Apr-Feb May-Feb Jun-Feb Aug-Jan Sep-Jan Sep-DecICER ($.QAL Y)\nMonths of RSV vaccine dosingICER: RSVpreF vs. Natural History\n59▪RSVpreF vaccine may improve RSV outcomes but will also increase costs\n–Base case incremental cost -effectiveness (ICER) ratio : $400,304/QAL Y\n•Year -round dosing \n•Typical RSV seasonality (based on pre -pandemic years) in most of the continental United \nStates\n–Work group felt that this vaccine would not be cost -effective under the base case conditions\n▪Cost -effectiveness would improved by using a seasonal dosing strategy\n–September through January in most of the continental US based on typical (pre -pandemic) \nRSV seasonality\n▪Work Group unanimously supported use of a seasonal dosing strategyWG interpretations: Resource Use\nQAL Y: Quality -Adjusted Life -Year\nCost -effectiveness model assumes typical RSV seasonality (based on pre -pandemic years) in most of the continental United States.\n60▪Is Pfizer Maternal RSVpreF vaccine use among pregnant people \nat 32–36 weeks gestation a reasonable and efficient allocation of \nresources?\n▪Work Group responses were based on seasonal dosing for RSVpreF vaccine (i.e., \nSeptember -January in most of the continental United States)Resource Use\nNo Probably No Probably Yes Yes Varies Don’t know\nMinority Opinion Majority Opinion\n61\nEtR Domain: Equity\nWhat would be the impact of the intervention on health equity?\n62▪National studies of death certificates found higher rates of RSV -\nassociated deaths among non -Hispanic Black children compared with \nnon -Hispanic White infants and children aged 1 –4 years1\n▪ICU admission rates for RSV among Non -Hispanic Black infants <6 \nmonths old were 1.2 –1.6x higher than among Non -Hispanic White infants2\n▪RSV hospitalization rates 4 –10x higher among Alaska Native and \nAmerican Indian children ages <24 months than the rate in the general \npopulation3 \n–This study was limited to specific populations and might not be broadly \nrepresentative of risk in all Alaska Native and American Indian childrenEquity summary: Incidence of RSV disease by race and \nethnicity in infants and children\n1. Hansen et al. The Use of Death Certificate Data to Characterize Mortality Associated With Respiratory Syncytial Virus, Unspecified Bronchio litis, and Influenza in the United \nStates, 1999 -2018 J Infect Dis. 2022 Aug 15;226(Supplement 2): S255 –S266.\n2 Unpublished data from RSV -NET, CDC. \n3 Atwell et al. RSV Among American Indian and Alaska Native Children: 2019 to 2020 Pediatrics. 2023 Aug 1;152(2):e2022060435\n63▪By federal law, all states provide Medicaid coverage for pregnancy -related services to \npregnant women with incomes up to 138% of the federal poverty level1\n▪In 2021, 41.0% of mothers had Medicaid at the time of birth2\n▪If recommended, ACIP will vote on a Vaccines for Children resolution for the Pfizer \nRSV vaccine for pregnant people <19 years of age\n▪After October 1, 2023, when the Inflation Reduction Act provisions become effective, \nstate Medicaid agencies will be required to cover vaccines and their administration \nwithout cost -sharing for nearly all full -benefit adult beneficiaries covered under \ntraditional Medicaid, if the CDC/ACIP recommendations applyEquity summary: Medicaid coverage for pregnant people \nand vaccines during pregnancy\n1Medicaid Coverage for Women | KFF\n2 2023 Medicaid and CHIP Beneficiary Profile: Enrollment, Expenditures, Characteristics, Health Status, and Experience\n64▪Under the Affordable Care Act and its implementing regulations, ACIP \nrecommendations that have been adopted by CDC “with respect to the individual \ninvolved” and are “listed on the Immunization Schedules of the Centers for Disease \nControl and Prevention” generally are required to be covered by group health plans \nand health insurance issuers offering group or individual health insurance coverage \nwithout imposing any cost -sharing requirements (such as a copayment, coinsurance, \nor deductible)Equity summary: Other insurance coverage for vaccines \nduring pregnancy\nACIP Shared Clinical Decision -Making Recommendations | CDC\n65▪What would be the impact of Pfizer Maternal RSVpreF vaccine \non health equity?  Answers ranged, no majorityEquity\nReduced\nProbably reduced\nProbably no impact\nProbably increased\nIncreased\nVaries\nDon’t know\n2ndmost common Most common 3rd most common\n66\nSummary\n67Evidence to Recommendations ( EtR ) framework\nEtR Domain Question(s) Work Group Judgements\nPublic Health Problem Is the problem of public health importance? Yes\nBenefits and Harms How substantial are the desirable anticipated effects? Large\nHow substantial are the undesirable anticipated effects? Small\nDo the desirable effects outweigh the undesirable effects? Favors intervention\nValues Does the target population feel the desirable effects are large \nrelative to the undesirable effects?Probably yes\nIs there important uncertainty about, or variability in, how \nmuch people value the main outcomes?Probably not important \nuncertainty or variability/ \nProbably important \nuncertainty or variability\nAcceptability Is the intervention acceptable to key stakeholders? Yes\nFeasibility Is the intervention feasible to implement? Yes\nResource Use Is the intervention a reasonable and efficient allocation of \nresources?Probably yes, with seasonal \ndosing\nEquity What would be the impact of the intervention on health \nequity?Ranged from probably no \nimpact to increased\n68Evidence to Recommendations framework \nSummary: Work Group interpretations\nBalance of \nConsequencesUndesirable\nconsequences\nclearly\noutweigh\ndesirable\nconsequences\nin most \nsettingsUndesirable\nconsequences\nprobably\noutweigh\ndesirable\nconsequences\nin most settingsThe balance\nbetween\ndesirable\nand \nundesirable\nconsequences\nis closely\nbalanced or\nuncertainDesirable\nconsequences\nprobably\noutweigh\nundesirable\nconsequences\nin most settingsDesirable\nconsequences\nclearly\noutweigh\nundesirable\nconsequences\nin most settingsThere\nis insufficient\nevidence\nto determine\nthe balance of\nconsequences\nMinority Opinion Majority Opinion\n69Evidence to Recommendations framework\nSummary: Work Group interpretations\nType of \nRecommendationWe do not \nrecommend the \ninterventionWe recommend the \nintervention for \nindividuals based on \nshared clinical \ndecision -makingWe recommend the \nintervention\nMinority Opinion Majority Opinion\n70▪Majority of Work Group was supportive of intervention with Pfizer maternal RSVpreF \nvaccine for pregnant people with dosing during the approved dosing interval (32 –36 \nweeks gestation) \n–Found the data on preterm birth when assessed among those vaccinated during the \napproved dosing interval (32 –36 weeks gestation) to be reassuring \n–Felt the approved dosing interval (32 –36 weeks gestation) reduces the potential risk \nof preterm birth and the potential for complications from preterm birth, which is \ntheir major safety concern\n▪All Work Group members endorsed the importance of post -introduction vaccine safety \nmonitoringWork Group considerations: Benefit and harms\n71▪Unanimously supported use of a seasonal dosing strategy which would maximize \nbenefits and cost -effectiveness \n▪Supported that RSVpreF vaccine dosing should occur during September –January in \nmost of the continental United States \n▪Felt that jurisdictions in which RSV seasonality differs from most of the continental US \nshould have flexibility regarding start and stop of administration of RSVpreF vaccine in \npregnant peopleWork Group considerations: Seasonal dosing\n72▪Pregnant people should have options for RSV prevention\n–Nirsevimab may not be readily available in all settings \n–Pregnant people and their providers may have preferences regarding these two \nproducts\n▪Pregnant people should be made aware that they can either receive RSVpreF vaccine \nduring pregnancy or nirsevimab can be given to the infant, but most infants will not \nneed both\n▪Pregnant people should be informed regarding the risks and benefits of both products \nbefore making a decisionWork Group considerations: RSVpreF vaccine is one of two \navailable preventive products for RSV in infants\n73▪Most work group members support a full recommendation\n–Approved dosing interval (32 –36 weeks) reduces the potential risk of and complications from preterm birth\n–Importance of clear vaccine recommendations\n–Providers who will help pregnant people decide which product to receive generally have less familiarity with the \ndata than ACIP\n–SCDM can be confusing to providers, hard to implement for providers, can lead to lower vaccine confidence and \nuptake of vaccination, and could potentially influence support for the vaccine in lower and middle income \ncountries\n▪Minority supported a recommendation with SCDM \n–Without SCDM, a full recommendation could result in some providers recommending RSVpreF vaccine during \npregnancy without discussing with pregnant patients that nirsevimab is an option\n–Potential risk for preterm birth (and neuroinflammatory events)\n–Same vaccine is recommended under SCDM for adults ages 60 years and older\n▪ACIP generally makes SCDM recommendations when individuals may benefit from \nvaccination, but broad vaccination of people in that group is unlikely to have \npopulation -level impactsWork Group considerations: Full vs shared clinical decision making \n(SCDM) recommendation for Pfizer maternal RSVpreF vaccine during \nthe approved dosing interval (32 –36 weeks gestation)\n74▪Currently there are no data available on:\n–Efficacy of the first lifetime dose during subsequent pregnancies\n–Safety of additional doses given in subsequent pregnancies\n▪Work Group felt that it was too early to decide whether additional doses should be \ngiven in subsequent pregnancies given the lack of data\n▪Additional data are needed to inform whether additional doses in subsequent \npregnancies would be indicated, and recommendations can be updated in the futureWork Group considerations: Additional vaccine doses in \nsubsequent pregnancies\n75▪Maternal RSV vaccine is recommended for pregnant people during 32 \nthrough 36 weeks gestation, using seasonal administration, to prevent \nRSV lower respiratory tract infection in infantsProposed voting language\n76Jefferson Jones\nLauren Roper \nMeredith McMorrow \nMila Prill \nMonica Godfrey \nMichael Melgar\nAmadea Britton\nAmanda Payne \nMegan Wallace\nDanielle Moulia\nMorgan Najdowski \nDavid Hutton Jamison Pike \nAndrew Leidner \nIsmael Ortega -Sanchez \nKaren Broder\nNaomi Tepper\nHeidi Moline\nAmber Winn\nMonica Patton\nJenny Milucky\nFiona Havers \nRebecca Morgan \nDoug Campos -OutcaltPatricia Wodi\nSascha Ellington\nMegan Lindley\nFangjun Zhou\nSarah Meyer\nDavid Hutton\nBarbara Mahon\nAron Hall\nCoronavirus and Other \nRespiratory Viruses Division\nImmunization Services \nDivision Acknowledgements \n77▪We acknowledge that not every person who can become pregnant identifies as a \nwoman. Although we try to use gender -neutral language as often as possible, much of \nthe research available currently refers only to “women” when discussing the ability to \nbecome pregnant. When citing research, we refer to the language used in the study. In \nthese cases, “woman” refers to someone who was assigned female at birth. For clarity \nin terminology, “maternal” is used to identify the person who is pregnant or \npostpartum throughout this presentation; the authors are aware that pregnancy is not \nequated with the decision to parent nor do all parents who give birth identify as \nmothers.Note\n78\nFor more information, contact CDC\n1-800 -CDC -INFO (232 -4636)\nTTY:  1 -888 -232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention.\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\n\n79\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nGrading of Recommendations, Assessment, Development, \nand Evaluation (GRADE): \nPfizer Maternal RSVpreF Vaccine \nUpdate: September 6, 2023\n80Evidence Retrieval, conducted as of April 10, 2023\n*Medline (OVID), Embase (OVID), Cochrane Library, CINAHL ( EbscoHost ), Scopus, clinicaltrials.govRecords screened*\n(n=161)Duplicates removed\n(n=7)\nStudies irrelevant\n(n=139)Full text studies \nassessed for \neligibility\n(n=12)Studies excluded\n(n=10)\n7 wrong intervention\n3 wrong patient population\nRecords included \nin evidence \nsynthesis \n(n=2)\n81▪High certainty: We are very confident that the true effect lies close to that of the \nestimate of the effect.\n▪Moderate certainty: We are moderately confident in the effect estimate: The true \neffect is likely to be close to the estimate of the effect, but there is a possibility that it \nis substantially different.\n▪Low certainty: Our confidence in the effect estimate is limited: The true effect may be \nsubstantially different from the effect estimate.\n▪Very low certainty: We have very little confidence in the effect estimate: The true \neffect is likely to be substantially different from the estimate of the effect.GRADE Evidence Type\nNOTE: Evidence type is not measuring the quality of individual studies, but how much certainty we \nhave in the estimates of effect across each outcome.\n82▪Initial evidence type (certainty level) determined by study design\n–Initial evidence high certainty: A body of evidence from randomized \ncontrolled trials\n–Initial evidence low certainty: A body of evidence from observational \nstudies\n▪The certainty of evidence may be downgraded due to risk of bias, \ninconsistency, indirectness, imprecision, or publication bias. For non -\nrandomized studies, the certainty may be rated up for presence of dose -\nresponse gradient, large or very large magnitude of effect, and opposing \nresidual confounding.GRADE Evidence Type\nNOTE: Evidence type is not measuring the quality of individual studies, but how much certainty we \nhave in the estimates of effect across each outcome.\n83\nBenefits\n84Vaccine efficacy methods\n*8 participants (3 in the vaccine group and 5 in the placebo group) received injection at >36 weeks gestation and were includ ed in the analysisDosing interval Number of \nParticipantsVE Formula Outcomes Reference\nPhase 3 trial, Trial \ndosing interval \n(24–36 weeks)*Vaccine: 3495\nPlacebo: 34801–(P/[1 –P]), where P is the number of \ncases in the RSVpreF group divided by \nthe total number of cases•Medically attended RSV -associated lower \nrespiratory tract infection in infants\n•Hospitalization for RSV -associated lower \nrespiratory tract infection in infants\n•All-cause medically attended lower \nrespiratory tract infection in infants Kampmann et al. and \nVRBPAC briefing \ndocument\nPhase 3 trial, Trial \ndosing interval \n(24–36 weeks)*Vaccine: 3495\nPlacebo: 34801–(P/[1 –P]), where P is the number of \ncases in the RSVpreF group divided by \nthe total number of cases•ICU admission from RSV hospitalization in \ninfants\n•Mechanical ventilation from RSV \nhospitalization in infants\n•All-cause hospitalization for lower \nrespiratory tract infection in infants Post -hoc analysis, \ndata provided by the \nmanufacturer for \nGRADE\nPhase 3 trial, \nApproved dosing \ninterval (32 –36 \nweeks) Vaccine: 1572\nPlacebo: 15391-(hP/[1 -P]), where P is the number of \ncases in the RSVpreF group divided by \nthe total number of cases and h is the \nratio of number of participants at risk in \nthe placebo group to the number of \nparticipants at risk in the RSVpreF groupAll efficacy outcomes Post -hoc analysis, \ndata provided by the \nmanufacturer\n85▪Pfizer phase 3 randomized controlled trial (RCT), MATISSE1\n▪Trial locations: Argentina, Australia, Brazil, Canada, Chile, Denmark, Finland, Gambia, Japan, Republic of \nKorea, Mexico, Netherlands, New Zealand, Philippines, South Africa, Spain, Taiwan, United States\n–45% of participants from United States\n▪Study enrollment and efficacy follow -up occurred June 17, 2020, to October 2, 2022\n▪Data evaluated: data cut -off September 30, 2022; mean follow -up in infant participants 11.97 months \nafter birth (range: 0.0, 24.3)\n▪Infant evaluable efficacy set: 3,495 in vaccine arm; 3,480 in placebo arm\n▪Exclusion criteria of certain conditions may not represent all pregnant people and their infants in the \nUnited States \n▪Placebo was not a saline placebo, but a lyophile match to the vaccine consisting of excipients matched \nto those used in the RSVpreF vaccine formulation, minus the active ingredientsOutcome 1: Medically attended RSV -associated lower \nrespiratory tract infection in infants (n=1 study)\n1Kampmann B, Madhi SA, Munjal I, et al. Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants. N Engl J Med. 2023 Apr 5. doi: 10.1056/NEJMoa2216480 .\n86▪Medically attended visit (inclusive of inpatient and outpatient encounters) \nand ≥1:\n–Fast breathing: respiratory rate ≥60 bpm (<2 months of age [60 days]) or \n≥50 bpm (≥2 to 12 months of age)\n–SpO2 measured in room air <95%\n–Chest wall indrawing\n▪RSV RT -PCR –positive test result by Pfizer central laboratory or by \ncertified laboratory with NAAT for RSV \n▪Confirmed by endpoint adjudication committee (EAC)Outcome 1: Medically attended RSV -associated lower \nrespiratory tract infection in infants (n=1 study)\n87Outcome 1: Medically attended RSV -associated lower \nrespiratory tract infection in infants (n=1 study)\nRR= relative risk, CI=confidence interval\n1Vaccine efficacy was calculated as 1−(P/[1−P]), where P is the number of cases of illness in the RSVpreF group divided by the total number of cases of illness. At 90 days, 99.5% \nconfidence intervals (CIs) were used (determined by the alpha -spending function and adjusted with the use of the Bonferroni proc edure), and at later intervals, 97.58% CIs were \nused (based on a two -sided alpha level of 0.0483 adjusted with the use of the Bonferroni procedure). Efficacy is from full phase 3 trial data, using trial dosing interval (24 –36 weeks \ngestation).\n2This outcome did not meet success criterion using manufacturer calculated VE (lower bound of CI was <20%) Time period \nafter birthEvents/Vaccine\n(n/N)Events/Placebo\n(n/N)Vaccine efficacy (1 –RR)\n(95% CI)Manufacturer calculated \nvaccine efficacy1 (99.5% \nor 97.58% CI)\n0–90 days after \nbirth224/3495 56/3480 57.3% (31.3, 73.5) 57.1% (14.7, 79.8)\n0–120 days after \nbirth35/3495 81/3480 57.0% (36.2, 71.0) 56.8% (31.2, 73.5)\n0–150 days after \nbirth47/3495 99/3480 52.7% (33.3, 66.5) 52.5% (28.7, 68.9)\n0–180 days after \nbirth57/3495 117/3480 51.5% (33.7, 64.5) 51.3% (29.4, 66.8)\n88▪Medically attended visit (inclusive of inpatient and outpatient encounters) \nand ≥1:\n–Fast breathing (respiratory rate ≥70 (<2 month of age [60 days]) or ≥60 (≥2 \nto 12 months of age)\n–SpO2 measured in room air <93%\n–High -flow nasal cannula or mechanical ventilation\n–ICU admission for >4 hours\n–Unresponsive/unconscious\n▪RSV RT -PCR –positive test result by Pfizer central laboratory or by \ncertified laboratory with NAAT for RSV \n▪Confirmed by EACOutcome 1: Severe medically attended RSV -associated \nlower respiratory tract infection in infants (n=1 study)\nSpO2= Peripheral capillary oxygen saturation; RT -PCR = Real -time polymerase chain reaction; NAAT= nucleic acid amplification technolog y; EAC= endpoint adjudication committee\nBlue text denotes differences between definitions of severe medically attended RSV -associated lower respiratory tract infection and medically attended RSV -associated lower \nrespiratory tract infection .\n89Outcome 1: Severe medically attended RSV -associated \nlower respiratory tract infection in infants (n=1 study)\nRR= relative risk, CI= confidence interval\n1Vaccine efficacy was calculated as 1−(P/[1−P]), where P is the number of cases of illness in the RSVpreF group divided by the total number of cases of illness. At 90 days, 99.5% \nconfidence intervals (CIs) were used (determined by the alpha -spending function and adjusted with the use of the Bonferroni proc edure), and at later intervals, 97.58% CIs were \nused (based on a two -sided alpha level of 0.0483 adjusted with the use of the Bonferroni procedure). \nEfficacy is from full phase 3 trial data, using trial dosing interval (24 –36 weeks gestation).Time period \nafter birthEvents/Vaccine\n(n/N)Events/Placebo\n(n/N)Vaccine efficacy (1 –RR)\n(95% CI)Manufacturer calculated \nvaccine efficacy1 (99.5% or \n97.58% CI)\n0–90 days \nafter birth6/3495 33/3480 81.9% (56.8, 92.4) 81.8% (40.6, 96.3)\n0–120 days \nafter birth12/3495 46/3480 74.0% (51.1, 86.2) 73.9% (45.6, 88.8)\n0–150 days \nafter birth16/3495 55/3480 71.0% (49.6, 83.4) 70.9% (44.5, 85.9)\n0–180 days \nafter birth19/3495 62/3480 69.5% (49.1, 81.7) 69.4% (44.3, 84.1)\n90▪Measures of effect\n–Relative Risk: 0.487 (97.58% CI: 0.332, 0.706)\n–Absolute Risk1: 1,725 fewer per 100,000 (988 to 2,246 fewer); NNV: 58 (45, 101)\n–Absolute Risk2: 11,850 fewer per 100,000 (6,791 to 15,431 fewer); NNV: 8 (6, 15)\n–Absolute Risk3: 5,643 fewer per 100,000 (3,234 to 7,348 fewer); NNV: 18 (14, 31)\n▪Concerns in certainty assessment: \n–None\n▪Evidence type: HighGRADE: Medically attended RSV -associated lower \nrespiratory infection in infants (n=1 study)\n1Calculated using the observed outcomes in the placebo arm during the clinical trial follow -up (3.4%)\n2Calculated using rate from Lively 2019 JPIDS , 2004 -2009 from 3 New Vaccine Surveillance Network (NVSN) sites from Nov -Apr season, included if with acute respiratory infection\n(ARI), not restricted to lower respiratory tract infection (LRTI). \n3Calculated assuming 47.5% of ARI from Lively et al paper were LRTI ( Rainisch 2020 Vaccine )\nNNV= Number needed to vaccinate\n91▪Phase 3 RCT, MATISSE1\n▪A respiratory tract infection due to RSV that results in hospitalization\n▪Confirmed by endpoint adjudication committee (EAC)Outcome 2: Hospitalization for RSV -associated lower \nrespiratory tract infection in infants (n=1 study)\n1Kampmann B, Madhi SA, Munjal I, et al. Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants. N Engl J Med. 2023 Apr 5. doi: 10.1056/NEJMoa2216480.\n92Outcome 2: Hospitalization for RSV -associated lower \nrespiratory tract infection in infants (n=1 study)\nRR= relative risk, CI= confidence interval\n1Vaccine efficacy was calculated as 1 –(P/[1 –P]), where P is the number of cases in the RSVpreF group divided by the total number of cases. The confidence interval was adjusted \nusing the Bonferroni procedure and accounting for the primary endpoints results. As a secondary endpoint, the criterion for v accine efficacy was a\nlower bound of the confidence interval >0%. \n2This outcome did not meet success criterion using manufacturer calculated VE (lower bound of CI was <0%) \nEfficacy is from full phase 3 trial data, using trial dosing interval (24 –36 weeks gestation).Time period after \nbirthEvents/Vaccine\n(n/N)Events/Placebo\n(n/N)Vaccine efficacy \n(1 –RR) (95% CI)Manufacturer calculated \nvaccine efficacy1\n(99.17% CI)\n0–90 days after birth 10/3495 31/3480 67.9% (34.6, 84.2) 67.7% (15.9, 89.5)\n0–120 days after birth 15/3495 37/3480 59.6% (26.6, 77.8) 59.5% (8.3, 83.7)\n0–150 days after birth 17/3495 39/3480 56.6% (23.4, 75.4) 56.4% (5.2, 81.5)\n0–180 days after birth 19/3495 44/3480 57.0% (26.5, 74.8) 56.8% (10.1, 80.7)\n0–360 days after \nbirth238/3495 57/3480 33.6% (0.2, 55.8) 33.3% ( -17.6, 62.9)\n93▪Measures of effect\n–Relative risk: 0.432 (99.17% CI: 0.193, 0.899)\n–Absolute risk1: 718 fewer per 100,000 (128 to 1,020 fewer); NNV: 139 (98, 781)\n–Absolute risk2: 1,051 fewer per 100,000 (187 to 1,493 fewer); NNV: 95 (67, 535)\n▪Concerns in certainty assessment: \n–Serious concern for imprecision due to the width of the confidence interval \ncontaining estimates for which different policy decisions might be considered\n▪Evidence type: ModerateGRADE: Hospitalization for RSV -associated lower \nrespiratory tract infection in infants (n=1 study)\n1Absolute risk was calculated using the observed outcomes in the placebo arm during the available clinical trial follow -up. \n2Calculated using the rate of acute respiratory infection (ARI) hospitalizations for infants 0 -5 months (2016 -2020 NVSN, unpubli shed)  \n94Outcome 3: ICU admission from RSV hospitalization in \ninfants (n=1 study)\nRR= relative risk, CI= confidence interval\n1Vaccine efficacy was calculated as 1 –(P/[1 –P]), where P is the number of cases in the RSVpreF group divided by the total number of cases.\nEfficacy is from full phase 3 trial data, using trial dosing interval (24 –36 weeks gestation).Time period after \nbirthEvents/Vaccine\n(n/N)Events/Placebo\n(n/N)Vaccine efficacy   \n(1 –RR) (95% CI)Manufacturer calculated \nvaccine efficacy1(95% CI)\n0–90 days after birth 2/3495 6/3480 66.8% ( -64.3, 93.3) 66.7% ( -86.4, 96.7)\n0–150 days after \nbirth4/3495 6/3480 33.6% ( -135, 81.3) 33.3% ( -181.1, 86.2)\n0–180 days after \nbirth4/3495 7/3480 43.1% ( -94.2, 83.3) 42.9% ( -124.8, 87.7)\n95▪Measures of effect\n–Relative risk: 0.571 (95% CI: 0.123, 2.248)\n–Absolute risk1: 86 fewer per 100,000 (from 176 fewer to 251 more)\n–Absolute risk2: 285 fewer per 100,000 (from 583 fewer to 830 more)\n▪Concerns in certainty assessment: \n–Very serious concern for imprecision due to the width of the confidence interval \ncontaining estimates for which different policy decisions might be considered and \nfragility of the estimate\n▪Evidence type: LowOutcome 3: ICU admission from RSV hospitalization in \ninfants (n=1 study)\n1Absolute risk was calculated using the observed outcomes in the placebo arm during the available clinical trial follow -up.\n2Calculated using the rate of ICU admissions in hospitalizations from Arriola 2019 JPIDS and acute respiratory infection (ARI) hospitalizations for infants 0 -5 months (2016 -2020 \nNVSN, unpublished) \n96Outcome 4: Mechanical ventilation1from RSV \nhospitalization in infants (n=1 study)\nRR= relative risk, CI= confidence interval\nEfficacy is from full phase 3 trial data, using trial dosing interval (24 –36 weeks gestation)\n1 Invasive or non -invasive mechanical ventilation\n2 Using 0.5 offset to account for zero events in the vaccine arm\n3 Vaccine efficacy was calculated as 1 –(P/[1 –P]), where P is the number of cases in the RSVpreF group divided by the total numbe r of casesTime period after \nbirthEvents/Vaccine\n(n/N)Events/Placebo\n(n/N)Vaccine efficacy2\n(1 –RR) (95% CI)Manufacturer calculated \nvaccine efficacy3 (95% CI)\n0–90 days after \nbirth0/3495 4/3480 88.9% ( -105.4, 99.4) 100% ( -51.5, 100)\n0–150 days after \nbirth0/3495 4/3480 88.9% ( -105.4, 99.4) 100% ( -51.5, 100)\n0–180 days after \nbirth0/3495 5/3480 90.0% ( -63.6, 99.5) 100% ( -9.1, 100)\n97▪Measures of effect\n–Relative risk: 0.001 (95% CI: 0.001, 1.091)\n–Absolute risk1: 144 fewer per 100,000 (144 fewer to 13 more)\n–Absolute risk2: 209 fewer per 100,000 (209 fewer to 19 more)\n▪Concerns in certainty assessment: \n–Very serious concern for imprecision due to the width of the confidence interval \ncontaining estimates for which different policy decisions might be considered and \nfragility of the estimate\n▪Evidence type: LowOutcome 4: Mechanical ventilation from RSV \nhospitalization in infants (n=1 study)\n1Absolute risk was calculated using the observed outcomes in the placebo arm during the available clinical trial follow -up\n2Calculated using the rate of mechanical ventilations in hospitalizations from Arriola 2019 JPIDS and acute respiratory infect ion (ARI) hospitalizations for infants 0 -5 months (2016 -\n2020 NVSN, unpublished)  \n98▪Phase 3 RCT, MATISSE and Phase 2b RCT (unpublished, data obtained from \nmanufacturer)\n▪Phase 2b RCT1,2\n–Pregnant people ages 18 –49 in Argentina, Chile, South Africa and United States\n•Infant safety set: 114 in vaccine arm (phase 3 formulation); 116 in placebo arm\n▪1 RSV -associated death occurred in an infant in the placebo group recorded at day 120 \nafter birth in the Phase 3 study, no RSV -associated deaths occurred in the RSVpreF \ngroup\n▪No RSV -associated deaths were recorded in the Phase 2b study among those who \nreceived the phase 3 formulation or placebo\n▪Outcome not included in GRADEOutcome 5: RSV -associated death in infants (n=2 studies)\n1Simões EAF, Center KJ, Tita ATN, et al. Prefusion F Protein –Based Respiratory Syncytial Virus Immunization in Pregnancy. N Engl J Med. 2022 Apr 28. doi: \n10.1056/NEJMoa2106062.\n2https://www.clinicaltrials.gov/ct2/show/study/NCT04032093\n99▪Phase 3 RCT, MATISSE1\n▪Infant with any medically attended -RTI visit (inpatient or outpatient) AND\n–Fast breathing (respiratory rate ≥60 bpm for <2 months of age [<60 days of \nage] or ≥50 bpm for ≥2 to <12 months of age) OR\n–SpO2 <95% OR\n–Chest wall indrawingOutcome 6: All -cause medically attended lower respiratory \ntract infection in infants (n=1 study)\n100Outcome 6: All -cause medically attended lower respiratory \ntract infection in infants (n=1 study)\nRR= relative risk, CI= confidence interval\n1Vaccine efficacy was calculated as 1 –(P/[1 –P]), where P is the number of cases in the RSVpreF group divided by the total number of cases. The confidence interval was adjusted \nusing the Bonferroni procedure and accounting for the primary endpoints results. As a secondary endpoint, the criterion for v accine efficacy was a\nlower bound of the confidence interval >0%. Efficacy is from full phase 3 trial data, using trial dosing interval (24 –36 weeks gestation).\n2This outcome did not meet success criterion (lower bound of CI was <0%) Time period \nafter birthEvents/Vaccine\n(n/N)Events/Placebo\n(n/N)Vaccine efficacy \n(1 –RR) (95% CI)Manufacturer calculated \nvaccine efficacy1  (99.17% CI)\n0–90 days after \nbirth2186/3495 200/3480 7.4% ( -12.4, 23.7) 7.0% ( -22.3, 29.3)\n0–120 days after \nbirth2261/3495 278/3480 6.5% ( -10, 20.5) 6.1% ( -18.3, 25.5)\n0–150 days after \nbirth2331/3495 349/3480 5.6% ( -8.9, 18.1) 5.2% ( -16.5, 22.8)\n0–180 days \nafter birth2392/3495 402/3480 2.9% ( -10.7, 14.8) 2.5% ( -17.9, 19.4)\n0–360 days \nafter birth2504/3495 531/3480 5.5% ( -5.8, 15.5) 5.1% ( -12.1, 19.6)\n101▪Measures of effect\n–Relative risk: 0.975 (99.17% CI: 0.806, 1.179)\n–Absolute risk*: 289 fewer per 100,000 (2,241 fewer to 2,068 more)\n▪Concerns in certainty assessment\n–Serious concern for imprecision due to the width of the confidence interval \ncontaining estimates for which different policy decisions might be considered\n▪Evidence type: ModerateGRADE: All -cause medically attended lower respiratory \ntract infection in infants (n=1 study)\n*Absolute risk was calculated using the observed outcomes in the placebo arm during the available clinical trial follow -up. Abso lute risk estimates should be interpreted in this \ncontext.\n102Outcome 7: All -cause hospitalization for lower respiratory \ntract infection in infants (n=1 study)\nRR= relative risk, CI= confidence interval\n1 Vaccine efficacy was calculated as 1 –(P/[1 –P]), where P is the number of cases in the RSVpreF group divided by the total numbe r of cases.\nEfficacy is from full phase 3 trial data, using trial dosing interval (24 –36 weeks gestation).Time period \nafter birthEvents/Vaccine\n(n/N)Events/Placebo\n(n/N)Vaccine efficacy \n(1 –RR) (95% CI)Manufacturer calculated \nvaccine efficacy1(95% CI)\n0–90 days \nafter birth35/3495 55/3480 36.6% (3.4, 58.4) 36.4% (1.0, 59.6)\n0–150 days \nafter birth47/3495 67/3480 30.2% ( -1.10, 51.8) 29.9% ( -3.4, 52.7)\n0–180 days \nafter birth54/3495 76/3480 29.3% (0, 49.9) 28.9% ( -2.0, 50.8)\n103▪Measures of effect\n–Relative risk: 0.711 (95% CI: 0.492, 1.020)\n–Absolute risk*: 631 fewer per 100,000 (from 1,109 fewer to 44 more)\n▪Concerns in certainty assessment\n–Serious concern for imprecision due to the width of the confidence interval \ncontaining estimates for which different policy decisions might be considered\n▪Evidence type: ModerateOutcome 7: All -cause hospitalization for lower respiratory \ntract infection in infants (n=1 study)\n*Absolute risk was calculated using the observed outcomes in the placebo arm during the available clinical trial follow -up. Abso lute risk estimates should be interpreted in this \ncontext.\n104\nHarms\n105▪Phase 3 RCT, MATISSE (unpublished, data obtained directly from \nmanufacturer)\n–Maternal safety set: 3,682 participants in vaccine arm; 3,675 in placebo arm\n▪Phase 2b RCT (unpublished, data obtained directly from manufacturer)\n–Maternal safety set: 115 participants in vaccine arm (phase 3 formulation); \n117 in placebo arm\n▪Follow up times for serious adverse events reported by maternal \nparticipants were from vaccination through 6 months after delivery \n(Phase 3) or throughout the study (Phase 2b)Outcome 8: Serious adverse events in pregnant people (n=2 \nstudies)\n106Outcome 8: Serious adverse events in pregnant people (n=2 \nstudies)\nCI= confidence interval\nVaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Briefing Document -FDATrial Events/Vaccine\n(n/N)Events/Placebo\n(n/N)Relative Risk (95% CI)\nPhase 3 598/3682 (16.2%) 558/3675 (15.1%) 1.07 (0.96, 1.19)\nPhase 2b 7/115 (6.1%) 14/117 (12.0%) 0.51 (0.21, 1.21)\nSerious adverse events in four vaccine recipients (pain in an arm followed by bilateral lower extremity pain, \npremature labor, systemic lupus erythematosus, and eclampsia) and in one placebo recipient (premature placental \nseparation) were assessed by the investigator as being related to the injection. Based on review of the event \nnarratives and temporal association of these events to vaccination, FDA agreed with the investigator’s \nassessments that there was a reasonable possibility that these events were related to the study intervention.\n107▪Measures of effect\n–Relative risk: 1.06 (95% CI: 0.95, 1.17)\n–Absolute risk*: 905 more per 100,000 (754 fewer to 2,564 more)\n▪Concerns in certainty assessment\n–Serious concern for imprecision due to the width of the confidence interval \ncontaining estimates for which different policy decisions might be considered\n–Serious concern for indirectness as 55% of the Phase 3 RCT and 62% of the Phase 2b \nRCT did not receive vaccine or placebo in the approved dosing interval (32 –36 weeks \ngestation). In the approved dosing interval, there is less opportunity for serious \nadverse events, including preterm birth/delivery, compared to the trial dosing \ninterval (24 –36 weeks gestation).\n▪Evidence type: LowGRADE: Serious adverse events in pregnant people (n=2 \nstudies)\n*Absolute risk was calculated using the observed outcomes in the placebo arm during the available clinical trial follow -up. Abso lute risk estimates should be interpreted in this \ncontext. CI= confidence interval\n108▪Phase 3 RCT, MATISSE and Phase 2b (unpublished, data obtained directly \nfrom manufacturer)\n▪Participants reported local and systemic reactions up to 7 days after \nvaccinationOutcome 9: Reactogenicity (grade 3+) in pregnant people \n(n=2 studies)\n109Outcome 9: Reactogenicity (grade 3+) in pregnant people \nTrial Outcome Events/Vaccine\n(n/N)Events/Placebo\n(n/N)Relative Risk (95% CI)\nPhase 3 Local events (grade 3+) 11/3663 (0.3%) 0/3639 (0%) 21.86 (1.29, 371.74)\nSystemic events (grade 3+) 83/3663 (2.3%) 83/3640 (2.3%) 0.99 (0.74, 1.34)\nPhase 2b Local events (grade 3+) 0/114 (0%) 0/117 (0%) 1.03 (0.02, 51.28)*\nSystemic events (grade 3+) 2/114 (1.8%) 4/117 (3.4%) 0.51 (0.10, 2.75)\nGrade 3: prevents daily routine activity. For redness or swelling is >10 cm. For vomiting, requires intravenous hydration. Fo r \ndiarrhea, includes 6 or more loose stools in 24 hours. Grade 4: requires emergency room visit or hospitalization; for redness\nincluded necrosis or exfoliative dermatitis; for swelling included necrosis. \n*Using 0.5 offset to account for zero events\nCI= confidence interval\n110▪Measures of effect\n–Relative risk: 0.97 (95% CI: 0.72, 1.31)\n–Absolute risk*:  69 fewer per 100,000 (648 fewer to 718 more)\n▪Concerns in certainty assessment: \n–Serious concern for indirectness as this data only includes systemic \nreactions . When selecting the a priori harm outcomes, the Work Group \ndefined reactogenicity as both local and systemic reactions.\n▪Evidence type: ModerateOutcome 9: Reactogenicity (grade 3+) in pregnant people \n(n=2 studies)\n*Absolute risk was calculated using the observed outcomes in the placebo arm during the available clinical trial follow -up. Abso lute risk estimates should be interpreted in this \ncontext. CI= confidence interval\n111▪Phase 3 RCT, MATISSE (unpublished, data obtained directly from \nmanufacturer)\n–Infant safety set: 3,568 in vaccine arm; 3,558 in placebo arm\n▪Phase 2b RCT (unpublished, data obtained directly from manufacturer)\n–Infant safety set: 114 in vaccine arm (phase 3 formulation); 116 in placebo \narmOutcome 10: Serious adverse events in infants (n=2 studies)\n112Outcome 10: Serious adverse events in infants (n=2 studies)\nVaccines and Related Biological Products Advisory Committee May 18, 2023 Meeting Briefing Document -FDA, CI= confidence intervalTrial Events/Vaccine\n(n/N)Events/Placebo\n(n/N)Relative Risk (95% CI)\nPhase 3 625/3568 (17.5%) 623/3558 (17.5%) 1.00 (0.90, 1.11)\nPhase 2b 41/114 (36.0%) 38/116 (32.8%) 1.10 (0.77, 1.57)\nNo serious adverse events in infants were considered by the investigators to be related to the vaccine. For infant deaths in the\nRSVpreF group, the FDA agreed with the investigator’s conclusions for 4 out of 5 of the infant deaths; however, for 1 case of\nextreme prematurity in an infant born to an 18 -year -old mother at 10 days after vaccination who died from prematurity -related \ncomplications, FDA was unable to exclude the possibility of the extreme prematurity and subsequent death being related to \nreceipt of the investigational product. No non -fatal SAEs in infant participants were considered related to maternal vaccination by \nFDA.\n113▪Measures of effect\n–Relative risk: 1.01 (95% CI: 0.91, 1.11)\n–Absolute risk*:  180 more per 100,000 (1,619 fewer to 1,979 more)\n▪Concerns in certainty assessment\n–Serious concern for imprecision due to the width of the confidence interval \ncontaining estimates for which different policy decisions might be considered\n–Serious concern for indirectness as 55% of the Phase 3 RCT and 62% of the Phase 2b \nRCT did not receive vaccine or placebo in the approved dosing interval (32 –36 weeks \ngestation). In the approved dosing interval, there is less opportunity for serious \nadverse events, including preterm birth/delivery, compared to the trial dosing \ninterval (24 –36 weeks gestation)\n▪Evidence type: LowGRADE: Serious adverse events in infants (n=2 studies)\nCI= confidence interval\n114▪Phase 3 RCT, MATISSE and Phase 2b (unpublished, data obtained directly \nfrom manufacturer)\n–Gestational age at birth <37 weeks and <34 weeksOutcome 11: Preterm births (n=2 studies)\n115\nOutcome: Preterm births (n=2 studies), Pfizer maternal \nRSVpreF vaccine\n*When reported as an adverse event of special interest, 202 preterm births occurred in the vaccine arm; the relative risk is minimally changed at 1.19 (0.98, 1.45) when using this \ncount\n**Using 0.5 offset to account for zero events in the vaccine arm\nCI= confidence intervalPublication Definition Events/Vaccine\n(n/N)Events/Placebo\n(n/N)Relative Risk (95% CI)\nPhase 3<34 weeks 21/3568 12/3558 1.75 (0.86, 3.54)\n<37 weeks 201*/3568 169/3558 1.19 (0.97, 1.45)\nPhase 2b<34 weeks 0/115 1/117 0.34 (0.01, 8.24)**\n<37 weeks 6/115 3/117 2.03 (0.52, 7.94)\n116▪Measures of effect\n–Relative risk: 1.20 (0.99, 1.46)\n–Absolute risk*:  936 more per 100,000 (from 47 fewer to 2,153 more)\n▪Concerns in certainty assessment:\n–Very se rious concern for imprecision due to the width of the confidence interval \ncontaining estimates for which different policy decisions might be considered and \nnot meeting optimal information size requirements\n–Serious concern for indirectness as 55% of the Phase 3 RCT and 62% of the Phase 2b \nRCT did not receive vaccine or placebo in the approved dosing interval (32 –36 weeks \ngestation). In the approved dosing interval, there is less opportunity for serious \nadverse events, including preterm birth/delivery, compared to the trial dosing \ninterval (24 –36 weeks gestation)\n▪Evidence type: Very lowOutcome: Preterm births (n=2 studies)\n*Absolute risk was calculated using the observed outcomes in the placebo arm during the available clinical trial follow -up. Abso lute risk estimates should be interpreted in this \ncontext. CI= confidence interval\n117\nGRADE additional slides\n118Inclusion/exclusion criteria for pregnant people -Phase 3 Trial\nInclusion Exclusion\nHealthy women ≤49 years of age who are \nbetween 24 0/7 and 36 0/7 weeks of gestation on \nthe day of planned vaccination, with an \nuncomplicated, singleton pregnancy, who are at \nno known increased risk for complications.\nWilling and able to comply with scheduled \nvisits, treatment plan, laboratory tests, and \nother study procedures.\nReceiving prenatal standard of care based on \ncountry requirements.\nHad a fetal anomaly ultrasound examination \nperformed at ≥18 weeks of pregnancy with no \nsignificant fetal abnormalities observed.\nDetermined by medical history, physical \nexamination, and clinical judgment to be \nappropriate for inclusion in the study.\nDocumented negative HIV antibody test, \nsyphilis test, and hepatitis B virus (HBV) surface \nantigen test during this pregnancy and prior to \nrandomization (Visit 1).\nIntention to deliver at a hospital or birthing \nfacility where study procedures can be \nobtained.\nExpected to be available for the duration of the \nstudy and can be contacted by telephone during \nstudy participation.\nParticipant is willing to give informed consent \nfor her infant to participate in the study.\nCapable of giving signed informed consent \nwhich includes compliance with the \nrequirements and restrictions listed in the \ninformed consent document (ICD) and in this \nprotocol OR If the maternal participant is \nilliterate, a thumbprinted informed consent \nmust be obtained, which must be signed and \ndated by an impartial witness who was present \nthroughout the entire informed consent process \nconfirming that the maternal participant has \nbeen informed of all pertinent aspects of the \nstudy.Prepregnancy body mass index (BMI) of >40 kg/m2. If prepregnancy BMI is not available, the BMI at the time of the first obstetric visit during the current pregnancy may be used.\nBleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindi cate intramuscular injection.\nHistory of severe adverse reaction associated with a vaccine and/or severe allergic reaction (e.g., anaphylaxis) to any compo nen t of the investigational product or any related vaccine.\nCurrent pregnancy resulting from in vitro fertilization.\nCurrent pregnancy complications or abnormalities at the time of consent that will increase the risk associated with the parti cipation in and completion of the study, including but not \nlimited to the following:\nPreeclampsia, eclampsia, or uncontrolled gestational hypertension.\nPlacental abnormality.\nPolyhydramnios or oligohydramnios.\nSignificant bleeding or blood clotting disorder.\nEndocrine disorders, including untreated hyperthyroidism or untreated hypothyroidism. This also includes disorders of glucose intolerance (e.g., diabetes mellitus type 1 or 2) antedating \npregnancy or occurring during pregnancy if uncontrolled at the time of consent.\nAny signs of premature labor with the current pregnancy or having ongoing intervention (medical/surgical) in the current preg nan cy to prevent preterm birth.\nPrior pregnancy complications or abnormalities at the time of consent, based on the investigator's judgment, that will increa se the risk associated with the participation in and completion \nof the study, including but not limited to the following:\nPrior preterm delivery ≤34 weeks' gestation.\nPrior stillbirth or neonatal death.\nPrevious infant with a known genetic disorder or significant congenital anomaly.\nMajor illness of the maternal participant or conditions of the fetus that, in the investigator's judgment, will substantially increase the risk associated with the maternal or infant participant's \nparticipation in, and completion of, the study or could preclude the evaluation of the maternal participant's response (inclu des positive serologic testing for regional endemic conditions \nassessed during routine maternal care, as per local standards of care and obstetric recommendations).\nCongenital or acquired immunodeficiency disorder, or rheumatologic disorder or other illness requiring chronic treatment with known immunosuppressant medications, including \nmonoclonal antibodies, within the year prior to enrollment.\nOther acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation o r behavior or laboratory abnormality that may increase the risk \nassociated with study participation or investigational product administration or may interfere with the interpretation of stu dy results and, in the judgment of the investigator, would make \nthe participant inappropriate for entry into this study.\nParticipation in other studies involving investigational drug(s) within 28 days prior to consent and/or during study particip ation.\nReceipt of monoclonal antibodies within the year prior to enrollment or the use of systemic corticosteroids for >14 days with in 28 days prior to study enrollment. Permitted treatments \ninclude the receipt of severe acute respiratory syndrome coronavirus 2 (SARS -CoV -2) monoclonal antibodies, prednisone doses of < 20 mg/day for ≤14 days and, inhaled/nebulized, intra -\narticular, intrabursal , or topical (skin or eyes) corticosteroids.\nCurrent alcohol abuse or illicit drug use. Note: Marijuana use is not considered an exclusion criterion for the study when el icited in participant screening, though it may be considered illicit \nin some locales.\nReceipt of blood or plasma products or immunoglobulin (Ig), from 60 days before investigational product administration, or pl ann ed receipt through delivery, with 1 exception, Rho(D) \nimmune globulin (e.g., RhoGAM), which can be given at any time.\nPrevious vaccination with any licensed or investigational RSV vaccine or planned. Note: Licensed COVID -19 vaccines or COVID -19 v accines authorized for temporary or emergency use will \nnot be prohibited during the course of this study.\nInvestigator site staff members directly involved in the conduct of the study and their family members, site staff members ot herwise supervised by the investigator, or Pfizer employees, \nincluding their family members, directly involved in the conduct of the study.\nParticipants who are breastfeeding at the time of enrollment.\n119Inclusion/exclusion criteria for infants -Phase 3 Trial\nInclusion Exclusion\nEvidence of a signed and dated informed consent document signed by \nthe parent(s)/legal guardian(s) OR If the infant participant's maternal \nparticipant/parent(s)/legal guardian(s) is illiterate, a thumbprinted\ninformed consent must have been obtained, which must have been \nsigned and dated by an impartial witness who was present throughout the \nentire informed consent process confirming that the maternal \nparticipant/parent(s)/legal guardian(s) has been informed of all pertinent \naspects of the study for herself (maternal participant) and her fetus/infant \nprior to taking part in the study.\nParent(s)/legal guardian(s) willing and able to comply with scheduled \nvisits, treatment plan, laboratory tests, and other study procedures.Infant who is a direct descendant (e.g., child or \ngrandchild) of the study personnel.\n120Inclusion/exclusion criteria for pregnant people -Phase 2b\nInclusion -Pregnant people Exclusion -Pregnant people\nHealthy women 18 to 49 years of age between 24 \nand 36 weeks of gestation on the day of planned \nvaccination, with an uncomplicated pregnancy, who \nare at no known increased risk for complications, and \nwhose fetus has no significant abnormalities \nobserved on ultrasound.\nWilling and able to comply with scheduled visits, \ntreatment plan, laboratory tests, and other study \nprocedures.\nReceiving prenatal standard of care.\nHad an ultrasound performed at >=18 weeks of \npregnancy.\nHad a negative urinalysis for protein and glucose at \nthe screening visit. Trace protein in the urine is \nacceptable if the blood pressure is also normal.\nDetermined by medical history, physical \nexamination, screening laboratory assessment, and \nclinical judgment to be appropriate for inclusion in \nthe study.\nDocumented negative human immunodeficiency \nvirus antibody, hepatitis B virus surface antigen, \nhepatitis C virus antibody, and syphilis tests at the \nscreening visit.\nBody mass index of </=40 kg/m2 at the time of the \nscreening visit.\nCapable of giving signed informed consent, which \nincludes compliance with the requirements and \nrestrictions listed in the informed consent document \nand in this protocol.\nExpected to be available for the duration of the \nstudy and willing to give informed consent for her \ninfant to participate in the study.Bleeding diathesis or condition associated with prolonged bleeding that would, in the opinion of the investigator, contraindi cate \nintramuscular injection.\nHistory of severe adverse reaction associated with a vaccine and/or severe allergic reaction to any component of the investig ational product \nor any related vaccine.\nHistory of latex allergy.\nHistory of any severe allergic reaction.\nParticipants with known or suspected immunodeficiency.\nCurrent pregnancy resulting from in vitro fertilization or other assisted reproductive technology.\nA prior history of or known current pregnancy complications or abnormalities that will increase the risk associated with the participant's \nparticipation in and completion of the study.\nMajor illness of the mother or conditions of the fetus that, in the investigator's judgment, will substantially increase the risk associated with \nthe participant's participation in, and completion of, the study or could preclude the evaluation of the participant's respon se.\nParticipant with a history of autoimmune disease or an active autoimmune disease requiring therapeutic intervention including but not \nlimited to systemic or cutaneous lupus erythematosus, autoimmune arthritis/rheumatoid arthritis, Guillain -Barré syndrome, multip le \nsclerosis, Sjögren's syndrome, idiopathic thrombocytopenia purpura, glomerulonephritis, autoimmune thyroiditis, giant cell arteritis \n(temporal arteritis), psoriasis, and insulin -dependent diabetes mellitus (type 1).\nOther acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation o r behavior or \nlaboratory abnormality that may increase the risk associated with study participation or investigational product administrati on or may \ninterfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inapp ropriate for \nentry into this study.\nParticipation in other studies involving investigational drug(s) within 28 days prior to study entry and/or during study part icipation.\nParticipants who receive treatment with immunosuppressive therapy including cytotoxic agents or systemic corticosteroids (suc h as for \ncancer or an autoimmune disease), or planned receipt of such treatment or agents during study participation. If systemic cort icosteroids \nhave been administered short term (<14 days) for treatment of an acute illness, participants should not be enrolled into the study until \ncorticosteroid therapy has been discontinued for at least 30 days before investigational product administration. Inhaled/nebu lized, intra \narticular, intrabursal , or topical (skin or eyes) corticosteroids are permitted.\nCurrent alcohol abuse or illicit drug use.\nReceipt of blood or plasma products or immunoglobulin, from 60 days before investigational product administration, or planned receipt \nthrough delivery, with 1 exception, Rho(D) immune globulin ( eg, RhoGAM), which can be given at any time.\nPrevious vaccination with any licensed or investigational RSV vaccine or planned receipt during study participation.\nLaboratory test results at the screening visit outside the normal reference value for pregnant women according to their trime ster in \npregnancy.\nParticipants who are breastfeeding at the time of the screening visit.\n121Inclusion/exclusion criteria for infants -Phase 2b\nInclusion -Infants Exclusion -Infants\nEvidence of a signed and dated informed consent document \nsigned by the parent(s).\nParent(s) willing and able to comply with scheduled visits, \ntreatment plan, laboratory tests, and other study procedures.Infant who is a direct descendant ( eg, child or grandchild) of the \nstudy personnel.\n122\nFigure 1. Enrollment, \nRandomization, \nAdministration of Vaccine or \nPlacebo, and Follow -up\nKampmann B, Madhi SA, Munjal I, et al. \nBivalent Prefusion F Vaccine in \nPregnancy to Prevent RSV Illness in \nInfants. N Engl J Med. 2023 Apr 5. doi: \n10.1056/NEJMoa2216480.\n123\nTable 1. Demographics of phase 3 trial\nKampmann B, Madhi SA, Munjal I, et al. \nBivalent Prefusion F Vaccine in Pregnancy to \nPrevent RSV Illness in Infants. N Engl J Med. \n2023 Apr 5. doi: 10.1056/NEJMoa2216480.\n124Severity scale for local reactions and systemic events \n(maternal participants)\nKampmann B, Madhi SA, Munjal I, et al. Bivalent Prefusion F Vaccine in Pregnancy to Prevent RSV Illness in Infants. N Engl J Med. 2023 Apr 5. doi: 10.1056/NEJMoa2216480.\n\n125Studies Included in the Review of Evidence\nLast name first \nauthor, Publication \nyearStudy \ndesignCountry Age \nmean \n(SD), \nyearsTotal Population N intervention N comparison Outcomes Funding \nSource\nKampmann B, \netal.plus unpublished \ndata obtained directly \nfrom the manufacturer RCT Argentina, Australia, \nBrazil, Canada, Chile, \nDenmark, Finland, \nGambia, Japan, \nRepublic of Korea, \nMexico, Netherlands, \nNew Zealand, \nPhilippines, South \nAfrica, Spain, Taiwan, \nUnited States29.0 \n(5.7)7,357 3,682 3,675 Medically attended \nRSV -associated lower \nrespiratory infection in \ninfants; Hospitalization \nfor RSV -associated \nlower respiratory tract \ninfection in infants; \nRSV -associated death \nin infants; All cause \nmedically attended \nlower respiratory tract \ninfection in infants; \nSerious adverse events \nin pregnant people; \nReactogenicity in \npregnant people; \nSerious adverse events \nin infants; Preterm \nbirthPfizer\nPfizer, Phase 2 Trial \nplus unpublished data \nobtained directly from \nthe manufacturer RCT Argentina, Chile, \nSouth Africa and the \nUnited States27.1\n(5.2)232 115 (phase 3 \nformulation)117 RSV -associated death \nin infants; Serious \nadverse events in \npregnant people; \nReactogenicity in \npregnant people;\nSerious adverse events \nin infants; Preterm \nbirth;Pfizer\n126Summary of Studies Reporting Outcome 1: Medically \nattended RSV -associated lower respiratory infection in \ninfants \nAbsolute difference was calculated using the observed outcomes in the placebo arm during the available clinical trial follow -up.Absolute difference estimates should be \ninterpreted in this context.Last name \nfirst author, \nPublication \nyearAge \nmean \n(SD), \nyearsN \ninterventionN \ncomparisonComparator \nVaccineAbsolute \ndifference/effect \nestimate \n(97.58% CI)Study \nlimitations \n(Risk of Bias)\nKampmann B, \net al.29.0\n(5.7)3495 3480 Placebo 1,725 fewer per \n100,000 (988 to \n2,246 fewer)None\n127Summary of Studies Reporting Outcome 2: \nHospitalization for RSV -associated lower respiratory \ntract infection in infants \nAbsolute difference was calculated using the observed outcomes in the placebo arm during the available clinical trial follow -up.Absolute difference estimates should be \ninterpreted in this context.Last name first \nauthor, \nPublication \nyearAge \nmean \n(SD), \nyearsN \ninterventio\nnN \ncomparisonComparato\nr VaccineAbsolute \ndifference/effect \nestimate \n(99.17% CI)Study \nlimitations \n(Risk of Bias)\nKampmann B, \net al.29.0 \n(5.7)3495 3480 Placebo 718 fewer per \n100,000 (128 to \n1,020 fewer)None\n128Summary of Studies Reporting Outcome 3: ICU \nadmission from RSV hospitalization in infants\nAbsolute difference was calculated using the observed outcomes in the placebo arm during the available clinical trial follow -up.Absolute difference estimates should be \ninterpreted in this context.Last name first \nauthor, \nPublication \nyearAge \nmean \n(SD), \nyearsN \ninterventionN \ncomparisonComparator \nVaccineAbsolute \ndifference/effect \nestimate (95% CI)Study \nlimitations \n(Risk of Bias)\nData received \ndirectly from \nthe \nmanufacturer29.0 \n(5.7)3495 3480 Placebo 86 fewer per \n100,000 (176 \nfewer to 251 \nmore)None\n129Summary of Studies Reporting Outcome 4: Mechanical \nventilation from RSV hospitalization in infants\nAbsolute difference was calculated using the observed outcomes in the placebo arm during the available clinical trial follow -up.Absolute difference estimates should be \ninterpreted in this context.Last name first \nauthor, \nPublication \nyearAge \nmean \n(SD), \nyearsN \ninterventio\nnN \ncomparisonComparato\nr VaccineAbsolute \ndifference/effect \nestimate (95% \nCI)Study \nlimitations \n(Risk of Bias)\nData received \ndirectly from \nthe \nmanufacturer29.0 \n(5.7)3495 3480 Placebo 144 fewer per \n100,000 (144 \nfewer to 13 more)None\n130Summary of Studies Reporting Outcome 5: RSV -associated \ndeath in infants \nLast name first \nauthor, \nPublication \nyearAge \nmean \n(SD), \nyearsN \ninterventionN \ncompariso\nnComparator \nVaccineAbsolute \ndifference/eff\nect estimateStudy \nlimitations \n(Risk of Bias)\nKampmann B, \net al.29.0\n(5.7)3495 3480 Placebo Not estimable \n1 death in a \nplacebo \nrecipientNone\nPhase 2b RCT, \nunpublished18-49 \n(range)114 116 Placebo Not estimable \n0 deaths in trialNone\n131Summary of Studies Reporting Outcome 6: All -cause \nmedically attended lower respiratory tract infection in \ninfants \nAbsolute difference was calculated using the observed outcomes in the placebo arm during the available clinical trial follow -up.Absolute difference estimates should be \ninterpreted in this context.Last name first \nauthor, \nPublication \nyearAge \nmean \n(SD), \nyearsN \ninterventio\nnN \ncomparisonComparator \nVaccineAbsolute \ndifference/effect \nestimate \n(99.17% CI)Study \nlimitations \n(Risk of Bias)\nKampmann B, \net al.29.0 \n(5.7)3495 3480 Placebo 289 fewer per \n100,000 (2,241 \nfewer to 2,068 \nmore)None\n132Summary of Studies Reporting Outcome 7: All -cause \nhospitalization for lower respiratory tract infection in \ninfants\nAbsolute difference was calculated using the observed outcomes in the placebo arm during the available clinical trial follow -up.Absolute difference estimates should be \ninterpreted in this context.Last name first \nauthor, \nPublication \nyearAge \nmean \n(SD), \nyearsN \ninterventio\nnN \ncomparisonComparator \nVaccineAbsolute \ndifference/effect \nestimate (95% \nCI)Study \nlimitations \n(Risk of Bias)\nData received \ndirectly from \nthe \nmanufacturer29.0 \n(5.7)3495 3480 Placebo 631 fewer per \n100,000 (1,109 \nfewer to 44 \nmore)None\n133Summary of Studies Reporting Outcome 8: Serious adverse \nevents in pregnant people \nLast name first \nauthor, \nPublication \nyearAge \nmean \n(SD), \nyearsN \ninterventionN \ncompariso\nnComparato\nr VaccineRelative \ndifference/effect \nestimateStudy \nlimitations \n(Risk of Bias)\nKampmann B, \net al.29.0 \n(5.7)3682 3675 Placebo RR: 1.07 (0.96, \n1.19)None\nPhase 2b RCT 27.1\n(5.2)115 117 Placebo RR: 0.51 (0.21, \n1.21)None\n134Summary of Studies Reporting Outcome 9: Reactogenicity \n(grade 3+) in pregnant people \nLast name \nfirst author, \nPublication \nyearAge \nmean \n(SD), \nyearsN \ninterventio\nnN \ncomparisonComparato\nr VaccineRelative \ndifference/effect \nestimateStudy \nlimitations \n(Risk of Bias)\nKampmann B, \net al.29.0 \n(5.7)3663 3640 Placebo RR: 0.99 (0.74, \n1.34)None\nPhase 2b RCT 27.1\n(5.2)114 117 Placebo RR: 0.51 (0.10, \n2.75)None\n135Summary of Studies Reporting Outcome 10: Serious \nadverse events in infants \nLast name first \nauthor, \nPublication yearAge median \n(range)N intervention N comparison Comparator \nVaccineRelative \ndifference/effect \nestimateStudy \nlimitations \n(Risk of Bias)\nKampmann B, \net al. 11.97 \nmonths \n(0.0, 24.3) 3568 3558 Placebo RR: 1.00 (0.90, \n1.11)None\nPhase 2b RCT 114 116 Placebo RR: 1.10 (0.77, \n1.57)None\n136Summary of Studies Reporting Outcome 11: Preterm birth\nLast name first \nauthor, \nPublication yearAge mean \n(SD)N intervention N comparison Comparator \nVaccineRelative \ndifference/effect \nestimateStudy \nlimitations \n(Risk of Bias)\nKampmann B, \net al.11.97 \nmonths \n(0.0, 24.3)3568 3558 Placebo RR: 1.19 (0.97, \n1.45)None\nPhase 2b RCT 115 117 Placebo RR: 2.03 (0.52, \n7.94)None\n137Grade Summary of Findings Table -Benefits\n№ of \nstudiesStudy designRisk of \nbiasInconsistency Indirectness ImprecisionOther \nconsiderationsIntervention ComparisonRelative\n(CI)Absolute\n(CI)Importance Certainty\nMedically attended RSV -associated lower respiratory infection in infants\n1 Randomized \nstudiesNot \nseriousNot serious Not serious Not serious None 57/3495 (1.6%) 117/3480 \n(3.4%)0.487 \n(97.58% CI: \n0.332, 0.706)1,725 fewer per \n100,000 (988 to \n2,246 fewer)Critical High\n23.1% 11,850 fewer per \n100,000 (6,791 to \n15,431 fewer)\n11.0% 5,643 fewer per \n100,000 (3,234 to \n7,348 fewer)\nHospitalizations RSV -associated lower respiratory infection in infants\n1 Randomized \nstudiesNot \nseriousNot serious Not serious Serious None 19/3495 (0.5%) 44/3480 (1.3%) 0.432 \n(99.17% CI: \n0.193, \n0.899)718 fewer per \n100,000 (128 to \n1,020 fewer)Critical Low\n1.9% 1,051 fewer per \n100,000 (187 to \n1,493 fewer)\nICU admission from RSV hospitalization\n1 Randomized \nstudiesNot \nseriousNot serious Not serious Very serious None 4/3495 (0.1%) 7/3480 (0.2%) 0.571 (95% \nCI: 0.123, \n2.248)86 fewer per \n100,000 (176 fewer \nto 251 more)Important Low\n0.7% 285 fewer per \n100,000 (583 fewer \nto 830 more)\n138Grade Summary of Findings Table -Benefits\n№ of \nstudiesStudy \ndesignRisk of \nbiasInconsistency Indirectness ImprecisionOther \nconsiderationsIntervention ComparisonRelative\n(CI)Absolute\n(95% CI)Importance Certainty\nMechanical ventilation from RSV hospitalization\n1 Randomized \nstudiesNot \nseriousNot serious Not serious Very serious None 0/3495 (0.0%) 5/3480 (0.1%) 0.001 \n(95% CI: \n0.001, \n1.091)144 fewer \nper 100,000 \n(144 fewer \nto 13 more)Important Low\n0.2% 209 fewer \nper 100,000 \n(209 fewer \nto 19 more)\nAll-cause medically attended lower respiratory tract infection in infants\n1 Randomized \nstudiesNot \nseriousNot serious Not serious Serious None 392/3495 \n(11.2%)402/3480 \n(11.6%)0.975 \n(99.17% CI: \n0.806, \n1.179)289 fewer \nper 100,000 \n(2,241 fewer \nto 2,068 \nmore)Important Moderate\nAll-cause hospitalization for lower respiratory tract infection in infants\n1 Randomized \nstudiesNot \nseriousNot serious Not serious Serious None 54/3495 (1.5%) 76/3480 (2.2%) 0.711 (95% \nCI: 0.492, \n1.010)631 fewer \nper 100,000 \n(1,109 fewer \nto 44 more)Important Moderate\n139Grade Summary of Findings Table -Harms\n№ of \nstudiesStudy designRisk of \nbiasInconsistency Indirectness ImprecisionOther \nconsiderationsIntervention comparisonRelative\n(95% CI)Absolute\n(95% CI)Importance Certainty\nSerious adverse events in pregnant women\n2 Randomized \nstudiesNot \nseriousNot serious Serious Serious None 605/3797 \n(15.9%)572/3792 \n(15.1%)1.06 \n(0.95, \n1.17)905 more \nper 100,000 \n(754 \nfewer to \n2,564 more)Critical Low\nReactogenicity (3+ or higher) in pregnant women\n2 Randomized \nstudiesNot \nseriousNot serious Serious Not serious None 85/3777 \n(2.3%)87/3757 (2.3%) 0.97 \n(0.72, \n1.31)69 fewer per \n100,000 \n(648 fewer \nto 718 more)Important Moderate\nSerious adverse events in infants\n2 Randomized \nstudiesNot \nseriousNot serious Serious Serious None 666/3682 \n(18.1%)661/3674 \n(18.0%)1.01 \n(0.91, \n1.11)180 more \nper 100,000 \n(1,619 fewer \nto 1,979 \nmore)Critical Low\nPreterm birth\n2 Randomized \nstudiesNot \nseriousNot serious Serious Very serious None 207/3683 \n(5.6%)172/3675 \n(4.7%)1.20 \n(0.99, \n1.46)936 more \nper 100,000 \n(47 fewer to \n2,153 more)Critical Very low", "summary": "1 Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. Evidence to Recommendations Framework Updates Pfizer Maternal RSVpreF Vaccine ACIP General Meeting September 22, 2023Katherine E. Fleming -Dutra, MD Co-lead,…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-september-22-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-09-22/06-Mat-Peds-Fleming-Dutra-508.pdf", "doc_date": "2023-09-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 139}
{"title": "07 Mat Peds Jones 508", "content": "1\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nProposed clinical considerations for maternal RSVPreF\nvaccine and nirsevimab\nJefferson Jones MD MPH FAAP\nCDR USPHS\nCo-Lead, Respiratory Syncytial Virus Vaccines -Pediatric/Maternal Work Group\nCoronavirus and Other Respiratory Viruses Division\nNational Center for Immunization and Respiratory Diseases\nSeptember 22, 2023\n2\nProposed clinical considerations \nfor use of maternal RSV vaccine\n3▪Maternal vaccine recommended for pregnant people during 32 through 36 \nweeks gestation, with seasonal administration\n–During September through January in most of the continental United States\n–In jurisdictions with seasonality that differs from most of the continental United \nStates (e.g., Alaska, jurisdictions with tropical climates), providers should follow \nstate, local, or territorial guidance on timing of administration\n▪Maternal RSVpreF vaccine may be simultaneously administered with \nother indicated vaccinations 1Proposed clinical considerations for use of maternal RSV \nvaccine\n1 https://www.cdc.gov/vaccines/hcp/acip -recs/general -recs/index.html. \nWork Group considerations for \nuse of both maternal RSV \nvaccine and nirsevimab\n5▪As proposed, maternal RSV vaccine recommendation is for administration \nbeginning at 32 weeks gestation\n▪From time of maternal vaccination, 14 days or more likely needed for \ndevelopment and transplacental transfer of maternal antibodies to \nprotect the infant,1 and nirsevimab is recommended for infants born \nwithin 14 days of vaccination\n▪Therefore, the earliest an infant can be born and have maternal vaccine -\ninduced protection is at 34 weeks gestation\n▪Infants born <34 weeks gestation will be recommended to receive \nnirsevimabMaternal vaccination and considerations for use of \nnirsevimab in infants born <34 weeks gestation\n1 https://www.cdc.gov/vaccines/pregnancy/vacc -during -after.html . \n6▪Protection from maternal vaccination may begin to wane after 3 or more \nmonths (e.g., influenza and COVID -19 vaccines) 1–3\n–Work Group members initially concerned that , with a year -round recommendation, infants born prior to the RSV \nseason and born to vaccinated mothers would require nirsevimab to boost protection when entering RSV season\n▪However, because maternal RSV vaccine administration is recommended \nduring September through January, most infants of vaccinated mothers \nwill be born during RSV season (i.e., born during October –March)\n▪Mothers of most infants born outside of RSV season (i.e., born during April \nthrough September) will not have been vaccinated, and nirsevimab will be \nrecommended for these infantsMaternal vaccination and considerations for use of \nnirsevimab in infants born outside of the RSV season\n1 Kampmann NEJM 2023 . 2Nunes F1000Res 2018 . 3 Zerbo Nat Commun 2023 . \n7▪Two products are available to protect infants from RSV lower respiratory tract \ninfection\n▪For infants born to vaccinated mothers, the addition of nirsevimab may \nprovide incremental protection, but this is unknown\n–No safety data on use of nirsevimab in infants born to vaccinated mothers, but nirsevimab trials \nincluded infants with maternal infection -induced antibodies and risk likely minimal\n▪For most infants, administering both products is not needed and would not be \na reasonable and efficient allocation of resources\n▪Documentation of maternal vaccination status may not be available to the \ninfant's healthcare providerWork Group considerations for use of both maternal RSV \nvaccine and nirsevimab\n8▪Most Work Group members felt that pregnant people should be aware that \nboth maternal vaccination and nirsevimab are options when deciding whether \nto be vaccinated\n–However, healthcare providers of pregnant people may not have time or feel \nequipped to discuss nirsevimab when counselling\n▪In rare situations flexibility is needed for providers to be able to provide \nnirsevimab when clinically warranted to infants born to vaccinated mothers\n–Conditions in pregnant people resulting in an inadequate immune response to vaccine or decrease \nin transplacental antibody transfer1\n–Infants who have undergone cardiopulmonary bypass, leading to loss of maternal antibodies2\n–Infants with sufficiently increased risk for severe disease to warrant nirsevimab because of the \npotential increased benefitWork Group considerations for use of both maternal RSV \nvaccine and nirsevimab ( cont )\n1Palmerira Clin Dev Immunol 2012 . 2 Feltes J Pediatr 2003 . \n9\nProposed clinical considerations for use \nof maternal RSV vaccine and \nnirsevimab\n10▪Either maternal vaccination or use of nirsevimab in the infant is \nrecommended to prevent RSV lower respiratory tract infection, but \nadministration of both products is not needed for most infants\n▪Healthcare providers of pregnant people should provide \ninformation onboth products and consider patient preferences when \ndetermining whether to vaccinate the pregnant patient or to not \nvaccinate and rely on administration of nirsevimab to the infant after birthProposed clinical considerations for maternal RSV vaccine \nand nirsevimab\n11Relative risks and benefits of maternal vaccination and \nnirsevimab\nMaternal RSV vaccine\nBenefits\n•Provides protection immediately after \nbirth\n•May be more resistant to virus mutation\n•Avoids injection of infant\nRisks\n•Protection reduced if fewer antibodies \nproduced or are transferred from mother \nto baby (e.g., mother \nimmunocompromised or infant born soon \nafter vaccination)\n•Potential risk of preterm birthNirsevimab\nBenefits\n•Studies of antibody levels suggest that \nprotection might wane more slowly\n•Can provide antibodies directly if infant \nreceives less antibodies from mother\n•No risk of adverse pregnancy outcomes\nRisks\n•Potentially limited availability during \n2023 -2024 RSV seasonBoth products are safe and effective in preventing RSV lower respiratory infection in infants\n12▪Nirsevimab is recommended for infants aged <8 months born \nduring or entering their first RSV season if\n–Mother did not receive RSV vaccine or unknown if mother received RSV vaccine\n–Mother vaccinated but infant born <14 days after vaccination\n▪Nirsevimab is not needed for most infants born ≥14 days after \nmaternal vaccinationProposed recommendations for use of nirsevimab in setting of \nan available maternal RSV vaccine\n13▪Nirsevimab can be considered in rare circumstances when, per the \nclinical judgment of the healthcare provider, the potential \nincremental benefit of administration is warranted\n–Infants born to pregnant people who may not mount an adequate immune response \nto vaccination (e.g., people with immunocompromising conditions) or have \nconditions associated with reduced transplacental antibody transfer (e.g., people \nliving with HIV infection)1\n–Infants who have undergone cardiopulmonary bypass, leading to loss of maternal \nantibodies2\n–Infants with substantial increased risk for severe RSV disease (e.g., \nhemodynamically significant congenital heart disease, intensive care admission and \nrequiring oxygen at discharge)Circumstances for which nirsevimab can be considered when \nmother has received RSV vaccine ≥14 days prior to birth\n1Palmerira Clin Dev Immunol 2012 .2Feltes J Pediatr 2003 .\n14Nirsevimab administration algorithm for children aged <8 months \non the day of administration\nNirsevimab \nnot neededNo\nAny criteria not metMeet all 3 following criteria? (yes/no)\n1.Either mother did not receive RSV vaccine during pregnancy ≥14 \ndays prior to birth or maternal RSV vaccine status unknown1\n2.Day of nirsevimab administration during October through March2\n3.Never previously received dose of nirsevimab3\nNirsevimab \nrecommendedYes\nAll 3 criteria met \n15Nirsevimab administration algorithm for children aged \n<8 months on the day of administration footnotes\n1For most infants age <8 months whose mother received RSV vaccine 14 or more days prior to birth, \nnirsevimab is not needed. Nirsevimab can be considered in rare circumstances when, per the clinical \njudgment of the healthcare provider, the potential incremental benefit of administration is warranted. \nThese situations include infants born to  pregnant people who may not mount an adequate immune \nresponse to vaccination (e.g., people with immunocompromising conditions) or have conditions associated \nwith reduced transplacental antibody transfer (e.g., people living with HIV infection), infants who have \nundergone cardiopulmonary bypass leading to loss of maternal antibodies, and infants with substantial \nincreased risk for severe RSV disease (e.g., hemodynamically significant congenital heart disease, intensive \ncare admission and requiring oxygen at discharge).\n2While the timing of the onset and duration of RSV season may vary, nirsevimab may be administered \nOctober through the end of March in the majority of the continental United States. Providers may adjust \ntiming of administration based on guidance from public health authorities (e.g., CDC, health departments) \nor regional medical centers. Although optimal timing of administration is just before the start of the RSV \nseason, nirsevimab may also be administered during the RSV season to infants and children who are age -\neligible. Infants born shortly before or during RSV season should receive nirsevimab within one week of \nbirth. Nirsevimab administration can occur during the birth hospitalization or in the outpatient setting. \nInfants with prolonged birth hospitalizations related to prematurity or other causes should receive \nnirsevimab shortly before or promptly after hospital discharge.\n16\nFor more information, contact CDC\n1-800 -CDC -INFO (232 -4636)\nTTY:  1 -888 -232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention.\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\n\n17Nirsevimab administration algorithm for children aged 8 through \n19 months on day of administration1\nNo\nNotall 3 criteria metMeet all 3 following criteria? (yes/no)\n1.Child at increased risk for RSV disease2\n2.Day of administration during October through March3\n3.Has not received 1 dose of nirsevimab during current \nRSV season and has not received 2 total doses4\nNirsevimab \nrecommendedNirsevimab not \nneededYes\nAll 3 criteria met \n18Nirsevimab administration algorithm for children aged 8 through 19 months on day of administration \nfootnotes\n1Children at increased risk for severe disease aged <8 months of age and entering their second RSV season \nshould receive nirsevimab. For example, a child born in March should receive their first RSV dose shortly \nafter birth; they may be entering their second RSV season at 7 months of age in October and should not wait \nuntil 8 months of age to receive nirsevimab. \n2Children aged 8 –19 months recommended to receive nirsevimab during their second RSV season by ACIP: \n-Children with chronic lung disease of prematurity who required medical support (chronic corticosteroid \ntherapy, diuretic therapy, or supplemental oxygen) any time during the 6 -month period before the start of \nthe second RSV season\n-Children with severe immunocompromise\n-Children with cystic fibrosis who have either 1) manifestations of severe lung disease (previous \nhospitalization for pulmonary exacerbation in the first year of life or abnormalities on chest imaging that \npersist when stable) or 2) weight -for-length <10th percentile\n-American Indian and Alaska Native children\n19Nirsevimab administration algorithm for children aged 8 through 19 months on day of administration \nfootnotes\n3While the timing of the onset and duration of RSV season may vary, nirsevimab may be administered \nOctober through the end of March in the majority of the continental United States. Providers may adjust \ntiming of administration based on guidance from public health authorities (e.g., CDC, health departments) \nor regional medical centers. Although optimal timing of administration is just before the start of the RSV \nseason, nirsevimab may also be administered during the RSV season to infants and children who are age -\neligible. Infants born shortly before or during RSV season should receive nirsevimab within one week of \nbirth. Nirsevimab administration can occur during the birth hospitalization or in the outpatient setting. \nInfants with prolonged birth hospitalizations related to prematurity or other causes should receive \nnirsevimab shortly before or promptly after hospital discharge.\n4Children at increased risk for severe disease should not receive more than two doses of nirsevimab (one \ndose [50mg or 100 mg depending on weight] for the first RSV season and one dose [two 100 mg injections] \nfor the second RSV season). Only one dose of nirsevimab is recommended per season (with exception for \nchildren who undergo cardiac surgery with cardiopulmonary bypass). Nirsevimab is recommended for \nchildren at increased risk for severe disease (as defined in footnote 4) during their first RSV season, including \nif aged 8 -11 months if the child has not received nirsevimab during that RSV season.", "summary": "1 Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. Proposed clinical considerations for maternal RSVPreF vaccine and nirsevimab Jefferson Jones MD MPH FAAP CDR USPHS Co-Lead, Respiratory Syncytial Virus Vaccines…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-september-22-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-09-22/07-Mat-Peds-Jones-508.pdf", "doc_date": "2023-09-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 19}
{"title": "08 Mat Peds Peacock 508", "content": "Centers for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nMaternal RSV Vaccine Implementation \nConsiderations\nGeorgina Peacock, MD, MPH\nImmunization Services Division\nCenters for Disease Control and Prevention\n▪Vaccine storage, handling, and administration\n▪Cost of vaccine\n▪Insurance coverage\n▪Supply and availability\n▪Complexity of immunization schedule\n▪Vaccine demand and coverage in pregnant people\n▪Obstetric and pediatric provider roles in vaccination decisions\n▪Immunization information systems\n▪Communication challengesMaternal RSV Implementation Considerations\n\n▪Overall clinical implementation similar to other vaccines\n–Stored at 2 ◦to 8◦C\n–Administered as a single dose through intramuscular route\n▪Additional steps required for dilution, \nincluding reconstitution of the lyophilized antigen \ncomponent with the sterile water diluent componentPfizer RSV Vaccine Storage, Handling, and Administration\nPackage Insert -ABRYSVO (STN 125769/26) | FDA\n▪Proposed recommendations to ACIP allow for simultaneous administration \nwith other recommended vaccines\n▪Increasing number of vaccines could lead to concerns for limited storage spaceSupplied as a kit with the following components:\n▪Cost of the Pfizer RSV vaccine is $295/dose, compared to ~$46 -52 for Tdap1\n–Cost is lower than infant nirsevimab ($495 private sector cost)\n▪Reimbursement and cost recovery challenges already identified by providers and \npractices as an implementation barrier for maternal immunization2Cost of Maternal RSV Vaccine\n1. Current CDC Vaccine Price List | CDC\n2.Immunization Practices of U.S. Obstetrician/Gynecologists for Pregnant Patients | ScienceDirect\nProvider Financial Concerns \nare a Leading Barrier to \nMaternal Immunization\nImmunization Practices of U.S. Obstetrician/Gynecologists for Pregnant Patients | \nScienceDirect\n\n▪Private insurance: 52% of pregnant people1\n–The Affordable Care Act (ACA) requires insurers to cover all ACIP -routinely recommended \nimmunizations for plan years that begin on or after the date that is one year after the date of the \nrecommendation2\n▪Medicaid: 41% of pregnant people1\n–After 10/1/23, when the Inflation Reduction Act provisions become effective, state Medicaid agencies \nwill be required to cover vaccines and their administration without cost -sharing for nearly all full -\nbenefit adult beneficiaries covered under traditional Medicaid, if the CDC/ACIP recommendations \napply3\n▪No insurance: 4% of pregnant people “self -pay” (likely uninsured)1\n–If recommended, ACIP will vote on a Vaccines for Children resolution for maternal RSV vaccine in \npeople aged <19 years\n–For people age 19+ years, limited availability (e.g., through 317 program)Insurance Coverage of Maternal RSV Vaccine\n1.Products -Data Briefs -Number 468 -May 2023 (cdc.gov) ; insurance status refers to source of payment for delivery. Another ~3% used other types of coverage\n2.42 U.S. Code §300gg –13 -Coverage of preventive health services | Cornell Law School\n3.Anniversary of the Inflation Reduction Act: Update on CMS Implementation | CMS\n▪ACIP has recommended nirsevimab as a routine immunization. Therefore, it will be \ncovered under the ACA without cost sharing by the patient starting in the effective \nplan year1\n▪Nirsevimab is included in the Vaccines for Children Program2\n–Eligible children (~50% of U.S. children) will be able to access nirsevimab at no costInsurance Coverage for Infant Nirsevimab\n1.42 U.S. Code §300gg –13 -Coverage of preventive health services | Cornell Law School\n2.Advisory Committee on Immunization Practices, Vaccines for Children Program | CDC\n▪No anticipated supply/demand mismatch\n▪Because the Pfizer maternal RSV vaccine is the same product in use for adults aged \n≥60 years, availability is expected shortly after ACIP recommendations\n▪Nirsevimab will likely be available late September/early October, but may not be \navailable in all pediatric settings this season\n–Efforts underway to increase number of birthing hospitals who will administer nirsevimabSupply and Availability of Maternal RSV Vaccine and \nNirsevimab During 2023 –2024 RSV Season\nIncreasing Complexity of Maternal Immunization Schedule\n▪Increasingly complex maternal immunization schedule, with different timing of \nvaccines based on season and/or gestational age (with seasonal timing varying in \nsome locations)\n▪Limited window for RSV vaccine administration\n▪Unclear willingness of pregnant people to accept multiple vaccines in pregnancy\n\nIn a survey of pregnant people, 12% said they would accept \nno vaccines, and 49% said they would accept 1 -2 vaccines\nCDC and University of Iowa/RAND survey, unpublished\n\nUptake of Vaccines among Pregnant People Has Declined \nand Disparities Persist\nFlu, Tdap, and COVID -19 Vaccination Coverage Among Pregnant Women –United States, April 2022 | CDC\n\n▪Decisions for whether to administer maternal RSV vaccine or infant nirsevimab will \nneed to be made during pregnancy\n▪Studies continue to demonstrate healthcare providers as pregnant people’s most \ntrusted source of information on vaccines, and provider recommendation is a strong \npredictor of vaccination1\n▪However, one survey showed that 2/3 of obstetricians did not feel providing \ninformation about routine childhood immunizations was part of their role2Obstetric Provider Role in Immunization Decisions\n1.Lutz C, et al. Understanding barriers and predictors of maternal immunization: Identifying gaps through an exploratory litera ture review. Vaccine 36 (2018): 7445 -7455\n2.Missed Opportunities: A National Survey of Obstetricians About Attitudes on Maternal and Infant Immunization | SpringerLink\n▪Recommendations for nirsevimab that are contingent upon knowledge of maternal \nvaccination status could be challenging if the pediatric provider does not receive the \nmaternal record\n▪Verbal report of vaccines received during pregnancy may not be reliable1\n▪Pediatric providers may need to make decisions on nirsevimab administration with \nincomplete information on maternal vaccination statusPediatric Provider Role in Immunization Decisions\n1.Tdap Vaccination Coverage During Pregnancy —Selected Sites, United States, 2006 –2015 | CDC\n▪State IIS vary in adult immunization capture\n▪Pregnancy status not identified in IIS, though could potentially consider RSV vaccine \nadministrations in adult women (<age 60 years) as a proxy\n▪Unable to link maternal and infant immunization records in the IIS\n–Clinical Decision Support for immunization unable to take into account maternal \nvaccination history for forecasting for infant nirsevimab immunization\n–Some state IIS policies limit ability of pediatric providers to review adult records, or \nrecords for individuals who are not their patientsImmunization Information Systems (IIS)\n▪Terminology: Vaccine (maternal product) vs. \nImmunization (infant product)\n▪Conveying potential risks and benefits of each \napproach, and helping the pregnant person make an \ninformed decision\n–Including potential but undetermined risk of preterm birth with \nmaternal immunization\n▪Discussing financial implications to patient in setting of \nuncertainties about coverage during the first year of \nimplementationCommunications Challenges\n\n▪Formative Research and Message Testing:\n–Focus groups and in -depth interviews with pregnant people and prenatal health \nproviders (in progress)\n–Surveys with parents of young children and pregnant and recently pregnant people\n▪Patient and provider education materials\n▪Digital partnerships with healthcare provider organizations\n▪Partnerships with organizations that serve pregnant people\n▪Social media across CDC’s platformsCommunications Activities\n\nThank You", "summary": "Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. Maternal RSV Vaccine Implementation  Considerations Georgina Peacock, MD, MPH Immunization Services Division Centers for Disease Control and Prevention ▪Vaccine storage,…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-september-22-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-09-22/08-Mat-Peds-Peacock-508.pdf", "doc_date": "2023-09-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 17}
{"title": "09 Mat Peds Schillie 508", "content": "Centers for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.Addition of an Addendum to the \n2023 Immunization Schedules for Children/Adolescents and Adults \nSarah Schillie, MD, MPH, MBA\nCAPT, US Public Health Service\nTeam Lead, Professional Education and Training, Immunization Services Division\nCenters for Disease Control and Prevention\nAdvisory Committee on Immunization Practices\nSeptember 22, 2023\nAtlanta, GA\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position o f the Centers for Disease \nControl and Prevention. Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and pre sentation use. No \nrights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nImmunization Schedules: Overview\n▪Two separate schedules\n–Child and adolescent schedule (age \nbirth through 18 years)\n–Adult schedule (age 19 years or older)\n▪Multiple sections that summarize \nand aid in implementation of \napproved ACIP policy \n–Cover Page\n–Tables\n–Notes\n–Appendix\n2 of 23 Immunization Schedules | CDC\nwww.cdc.gov/vaccines/schedules/index.html\n\nImmunization Schedules: Overview, cont.\n▪Published in 3 formats:\n–PDF, webpage, app\n▪Multiple professional organizations partner with CDC to approve schedules\n–American College of Physicians ( www.acponline.org )\n–American Academy of Family Physicians ( www.aafp.org )\n–American College of Obstetricians and Gynecologists ( www.acog.org )\n–American College of Nurse -Midwives ( www.midwife.org )\n–American Academy of Physician Associates ( www.aapa.org )\n–American Pharmacists Association ( www.pharmacist.com )\n–Society for Healthcare Epidemiology of America ( www.shea -online.org )\n–American Academy of Pediatrics ( www.aap.org )\n–National Association of Pediatric Nurse Practitioners ( www.napnap.org )\n▪Some professional organizations publish the schedules\n3 of 23\n4 of 23\n\n5 of 23\n6 of 23\n7 of 23\nTraditional Publication Timeline\nOctober November December January February\nACIP vote approves the \nimmunization schedulesProfessional organizations \napprove schedules\nDraft and clear MMWR reports (both \nschedules) and Annals of Internal \nMedicine report (adult schedule only)Schedules (3 formats),\nMMWR Notice to Readers, &\nAnnals of Internal Medicine \nreport published\n8 of 23\n▪Insurance reimbursement\n▪The ability of certain health care providers to administer \nimmunizations\n–Some states link pharmacists’ immunization authority to the schedule\n▪Health care provider knowledge and practices related to \nimmunization recommendationsImpacts of Timeliness of Schedule Publication\n9 of 23\n▪Must provide coverage for and must not impose any cost -sharing requirements \n(such as a copayment, coinsurance, or a deductible) for —\n“Immunizations for routine use in children, adolescents, and adults that have in \neffect a recommendation from the Advisory Committee on Immunization \nPractices of the Centers for Disease Control and Prevention…” “…considered in \neffect after it has been adopted by the Director of the Centers for Disease \nControl and Prevention, and a recommendation is considered to be for routine \nuse if it is listed on the Immunization Schedules of the Centers for Disease \nControl and Prevention)”\n▪ACA does not specify what defines the Immunization Schedule \n–Legally, CDC has discretion regarding what constitutes the immunization scheduleAffordable Care Act: Immunization Coverage\n10 of 23\n3-Pronged Approach to Address Schedule Timeliness, \nMaximize Utility\nImmediate \nStrategy\nAddition of \nAddenda will help \nbring the schedule \nup-to-dateShort -term \nStrategy\nPublish entirety of \nschedule soon after \nOctober ACIP voteLonger -term \nStrategy\nConsider sustainable approach to ensure \nschedule remains dynamic/responsive \nand current (proposal in early in CY24)\nEnsure partner engagement in \nplanning process\n11 of 23\nAddition of Addenda to 2023 Immunization Schedules\n▪Contain ACIP recommendations that occurred after the 2023 \nschedule was published\n▪Plan to release 2023 Immunization Schedules with Addenda next \nweek\n▪With this addition, all ACIP recommendations will formally be part of \nthe CDC Immunization Schedules\n12 of 23\n13 of 23\n14 of 23\n15 of 23\n16 of 23\n17 of 23\n18 of 23\n19 of 23\n20 of 23\n21 of 23\n▪Anticipate release of 2023 Immunization Schedules with \nAddenda next week\n–Formally incorporate all ACIP recommendations into 2023 CDC \nImmunization Schedule\n▪Plan for short -and long -term sustainable strategies to address \nschedule timeliness\n–Ensure partner engagementSummary\n22 of 23\nAcknowledgements \nImmunization Services Division and \nHealth Education and Communication Branch staff, especially: \n•Neil Murthy\n•Patricia Wodi\n•Rosa Herrera\n•Richard Quartarone\n•Akiko Wilson\n23 of 23\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the \nofficial position of the Centers for Disease Control and Prevention.Questions?\nAdditional Slides\n▪Adult Vaccine Assessment Tool\n▪Child and Adolescent Vaccine Assessment Tool\n▪Parent Friendly CDC Resources based off the Immunization Schedules", "summary": "Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-september-22-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-09-22/09-Mat-Peds-Schillie-508.pdf", "doc_date": "2023-09-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 32}
{"title": "01 COVID Daley 508", "content": "Centers for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nACIP COVID -19 Vaccines Work Group\nDr. Matthew F. Daley, Work Group Chair\nSept 12, 2023\n▪September 11, 2023: \n–FDA updated COVID -19 vaccine emergency use authorizations (EUAs)\n•Use of 2023 –2024 mRNA vaccines for all doses/indications administered to \nindividuals ages 6 months –11 years\n–FDA approved supplemental biologics license applications (BLAs)\n•Use of 2023 –2024 mRNA vaccines for all doses/indications administered to \nindividuals ages ≥ 12 yearsCOVID -19 vaccine update:\nFDA authorizations and approvals\n▪Updates to COVID -19 epidemiology and vaccine effectiveness, including in pregnant persons and \ninfants\n▪Infection -induced and hybrid immunity\n▪Summary and Work Group considerations\n–COVID -19 and pregnancy:\n•Pregnancy remains a risk factor for severe COVID -19 disease\n•COVID -19 vaccination improves outcomes for pregnant people and their infants\n–Infection -induced and h ybrid immunity:\n•Hybrid immunity likely provides better protection than either infection or vaccination alone.\n•Protection likely influenced by multiple factors (e.g., prior vaccine doses, infection, time since \nvaccination or infection) \n•Protection wanes over time after both infection and vaccinationJune ACIP Meeting Review\nJune 23, 2023\n▪Manufacturer data to inform monovalent XBB.1.5 containing vaccine update\n▪Modeling of pandemic outcomes in varied scenarios, demonstrating potential impact \nof new variants and varying vaccine/booster coverage\n▪Comprehensive review of COVID -19 vaccine safety\n▪Updated data on COVID -19 epidemiology, vaccine effectiveness, and benefit -risk \nassessment\n▪Epidemiology of post -COVID conditions \n▪COVID -19 vaccine cost -effectiveness analysis\n▪Evidence to Recommendations Framework\n–Work group discussed universal vs. risk -based strategies, reviewed additional data \non burden (by age group, presence of underlying condition)ACIP COVID -19 Work Group Meeting Review\nJuly –September 2023\n▪Current landscape of SARS -CoV -2 lineages Dr. Natalie Thornburg \n▪COVID -19 epidemiology Dr. Fiona Havers\n▪Post -COVID conditions Dr. Sharon Saydah\n▪COVID -19 Vaccine Effectiveness Update Dr. Ruth Link -Gelles\n▪Economic analysis of COVID -19 vaccination Dr. Lisa Prosser\n▪COVID -19 vaccine safety surveillance Dr. Nicola Klein\n▪Break\n▪Moderna 2023 –2024 COVID -19 vaccine Dr. Fran Priddy\n▪Novavax 2023 –2024 COVID -19 vaccine Dr. Filip Dubovsky\n▪Pfizer -BioNTech 2023 –2024 COVID -19 vaccine Dr. Kayvon ModjarradAgenda\nSeptember 12, 2023\nBreak\n▪Evidence to Recommendations Dr. Megan Wallace\n▪Overview of COVID -19 vaccine implementation Dr. Georgina Peacock \n▪Bridge access program Dr. Evelyn Twentyman\n▪Discussion\nBreak\nPUBLIC COMMENT\nBreak\nVote:\n2023 –2024 COVID -19 vaccines in persons ages 6 months and olderAgenda\nSeptember 12, 2023\nWork Group members\nACIP members\n▪Matthew Daley (chair)\n▪Beth Bell \n▪Grace Lee\n▪Keipp Talbot\n▪Oliver Brooks\nEx-officio/government members\n▪FDA: Rachel Zhang, Lucia Lee, Anuja Rastogi\n▪NIH: Chris Roberts, Michael Ison\n▪IHS: Uzo Chukwuma\n▪CMS: Jeff Kelman\n▪BARDA: Christine Oshansky\n▪HHS: Valerie Marshall\n▪CDC: Alan Lam\nCDC Leads\n▪Megan Wallace\n▪Joanna Regan\n7Liaisons\n▪AAFP: Jonathan Temte\n▪AAP: Sean O’Leary\n▪ACOG: Denise Jamieson (primary), \nLaura Riley (alternate)\n▪ACP: Jason Goldman\n▪ADS: Emily Kahn\n▪AGS: Ken Schmader\n▪AMA: Sandra Fryhofer\n▪ANA: Ruth Francis (alternate)\n▪APA: Richard Dang\n▪ASTHO: Marcus Plescia\n▪CSTE: Paul Cieslak, Christine HahnLiaisons, cont’d\n▪NACCHO: Matt Zahn (primary), \nJeff Duchin (alternate)\n▪NACI: Matthew Tunis (primary),    \nEva Wong (alternate)  \n▪NFID: Rob Schechter (primary),        \nBill Schaffner (alternate)\n▪NMA: Patricia Whitley -Williams\n▪SHEA: Preeti Mehrotra,                \nMarci Drees (alternate)\nConsultants\n▪Ed Belongia\n▪Hank Bernstein\n▪Kathy Edwards\n▪Robert Hopkins\n▪Lisa Jackson\n▪Kathy Kinlaw\n▪Dayna Matthew ▪Jennifer Nelson\n▪Kathleen Neuzil\n▪Stanley Perlman\n▪Peter Szilagyi\n▪Sarah Meyer\n▪Elisha Hall\n▪Danielle Moulia\n▪Monica Godfrey\n▪Hannah Rosenblum\n▪Katherine Fleming -Dutra\n▪Ruth Link -Gelles\n▪Lauren Roper \n▪Mary Chamberland\n▪Susan Goldstein\n▪Stephen Hadler\n▪JoEllen Wolicki\n▪Melinda Wharton\n▪Jessica MacNeil\n▪Amanda Cohn\n▪Brooke Aspinwall \n▪Latifa Boyce CDC participants\n8▪Amadea Britton\n▪Karen Broder \n▪Carolyn Bridges\n▪Allison Ciesla \n▪Nicole Dowling\n▪Daniel Drapeau\n▪Tarayn Fairlie\n▪Ashley Fowlkes\n▪Julianne Gee\n▪Samuel Graitcer\n▪Lisa Grohskopf\n▪Katherine Grusich\n▪Aaron Hall \n▪Demorah Hayes\n▪Rita Helfand\n▪Terri Hyde\n▪Jefferson Jones ▪Melisa Shah\n▪Tom Shimabukuro\n▪Jordan Singleton\n▪Laura Steinhardt\n▪John Su\n▪Natalie Thornburg\n▪Evelyn Twentyman \n▪Dennis Wang\n▪Raigan Wheeler\n▪Ryan Wiegand\n▪Patricia Yu\n▪Yon Yu▪Andrew Kroger\n▪Josephine Mak\n▪Lauri Markowitz\n▪Michael McNeil\n▪Michael Melgar\n▪Noelle -Angelique Molinari\n▪Morgan Najdowski\n▪Kristen Nordlund\n▪Sara Oliver \n▪Ismael Ortega -Sanchez\n▪Manisha Patel\n▪Pragna Patel\n▪Amanda Payne\n▪Georgina Peacock\n▪Jamison Pike \n▪Derrell Powers\n▪Sierra Scarbrough\nFor more information, contact CDC\n1-800 -CDC -INFO (232 -4636)\nTTY:  1 -888 -232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention.\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nThank you", "summary": "Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. ACIP COVID -19 Vaccines Work Group Dr. Matthew F. Daley, Work Group Chair Sept 12, 2023 ▪September 11, 2023:  –FDA updated COVID -19 vaccine emergency use authorizations…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-september-12-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-09-12/01-COVID-Daley-508.pdf", "doc_date": "2023-09-12", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 9}
{"title": "02 COVID Thornburg 508", "content": "Centers for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nCurrent landscape of SARS -CoV-2 lineages\nSeptember 2023\nNatalie J. Thornburg, PhD\nChief, Laboratory Branch\nCoronaviruses and Other Respiratory Viruses Division\nTrends in weighted lineage proportion estimates & Nowcast \nUnited States, May 27 –September 2, 2023\nhttps://covid.cdc.gov/covid -data-tracker/#variant -proportions Accessed 9/1/2023\nTwo-week period ending\nConvergent Evolution of Different Omicron Sub -lineages:\nKey changes in the spike receptor binding domain (RBD) detected since September 2022\nLineageSpike RBD (residues 333 -527) amino acid substitutions\n339\n§346\n§,¶368 444\n§,¶445\n¶446\n§,¶452\n§,¶460\n§,¶478 486\n§,¶490\n§,¶521\nReference sequence: BA.4/BA.5 D R L K V G R N K V F P\nBA.4.6, BA.5.2.6, BF.7, BF.11 — T——————————\nBQ.1 ——— T——— K————\nBQ.1.1 — T— T——— K————\nBA.2.75 H———— S L K— F——\nBN.1 H T——— S L K— F S—\nCH.1.1 H T— T— S— K— S——\nXBB, XBB.1 H T I— P S L K— S S—\nXBB.1.5, XBB.1.5.1, FD.2, XBB.1.9.1, \nXBB.1.9.2H T I— P S L K— P S—\nXBB.1.16, XBB.1.16.1 H T I— P S L K R P S—\nXBB.2.3 H T I— P S L K— P S S\nMa et al. MMWR to be published on June 15, 2023\n§Indicates sites of independent substitutions in at least two different evolutionary lineages.\n¶Indicates sites identified in a previous study associated with in vitro reductions in binding by monoclonal antibodies that were previously FDA -authorized.\nBolded sub -lineages are expanding in the United States as of June 10, 2023\nMore than 90% of circulating viruses have similar Spike receptor \nbinding domain sequences\nLineageSpike RBD (residues 333 -527) amino acid substitutions\n452 455 456 460 478 486 521\nReference sequence: XBB.1.5 L L F K K P P\nXBB.1.9 — — — — — S —\nXBB.1.5.70 — F L — — — —\nXBB.1.16 — — — — R — —\nEG, FL — — L — — — —\nEG.5 , EG.5.1.6 , FL.1.5 — — L — — — —\nXBB.1.16.6, XBB.1.16.9, FL.1.5.1, HN.1 — — L — R — —\nHV.1 R — L — — — —\nHK.3 — F L — — — —\nXBB.2.3 — — — — — — S\nXBB.1.16, XBB.1.16.1 — — — — R — —\nXBB.1.5 and XBB.1.16 Spike substitutions relative to \nBA.5\nReceptor \nbinding motif\nReceptor \nbinding domain\nN-terminal \ndomain\nRemainder of \nS1\nS2ACE2\nACE2XBB.1.5 XBB.1.16\nBA.2.86 is a descendent of BA.2\nNexstrain (Roemer / Neher )•Most closely related \nto BA.2\n•BA.2 and its lineages \ncirculated in spring \n2022 before BA.5 \nviruses\n\nBA.2.86 has >30 amino acid substitions in spike in \ncomparison to XBB.1.5\n▪>30 amino acid substitutions in Spike in comparison to XBB.1.5\n–Variation between sequences due to missing data and sequencing artifacts\n▪First detected in specimen collected in late July, 2023\n▪As of 9/6 detected in 7 clinical specimens in 7 US states and 1 additional state in \nwaste water\n▪Detected in 10 countries\n▪Small number of sequences \n\nReduction in pseudovirus neutralization is not detected \nusing sera from people infected with XBB lineage \nviruses\nQian Wang \nDr. David D. Ho lab\n\nNo reduction in BA.2.86 pseudovirus neutralization \nis observed after bivalent vaccination, or after 6 \nmonths with or without XBB infection\nLasrado et al. Neutralization Escape by SARS -CoV-2 Omicron Subvariant BA.2.86 | bioRxiv\n\nData generation with authentic viruses\n▪More than 90% of currently circulating viruses are XBB lineage viruses with 1 -2 \nadditional substitutions in RBD in comparison to XBB.1.5\n▪BA.2.86 is a newly detected lineage with > 30 amino acid substitutions in spike\n–Thus far, the number of viruses detected is still low\n–Sequence numbers are too low to calculate proportion (<0.05%)\n▪Preliminary pseudovirus neutralization data generated by multiple labs do not \nindicate a large reduction in neutralizing activity against BA.2.86\n▪CDC has generated a BA.2.86 isolates, is currently working on titrations before \nneutralization and will distribute to external laboratories for further examination\n▪More than 90% of currently circulating viruses are XBB lineage viruses with 1 -2 \nadditional substitutions in RBD in comparison to XBB.1.5\n▪BA.2.86 is a newly detected lineage with > 30 amino acid substitutions in spike\n–Thus far, the number of viruses detected is still low\n–Sequence numbers are too low to calculate proportion (<0.05%)\n▪Preliminary pseudovirus neutralization data generated by multiple labs do not \nindicate a large reduction in neutralizing activity against BA.2.86\n▪CDC has generated a BA.2.86 isolate, is currently working on titrations before \nneutralization and has begun distribution to external laboratories for further \nexaminationSummary\nFor more information, contact CDC\n1-800 -CDC -INFO (232 -4636)\nTTY:  1 -888 -232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention.\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.", "summary": "Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. Current landscape of SARS -CoV-2 lineages September 2023 Natalie J. Thornburg, PhD Chief, Laboratory Branch Coronaviruses and Other Respiratory Viruses Division Trends in…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-september-12-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-09-12/02-COVID-Thornburg-508.pdf", "doc_date": "2023-09-12", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 12}
{"title": "03 COVID Havers 508", "content": "Centers for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nCOVID -19–Associated Hospitalizations among \nInfants, Children and Adults —COVID -NET, January –\nAugust 2023\nACIP , September 12, 2023\nFiona P . Havers, MD, MHS\nTeam Lead, RESP -NET Hospitalization Surveillance Team\nSurveillance and Prevention Branch\nCoronavirus and Other Respiratory Viruses Division\n▪RESP -NET: COVID -NET, RSV -NET, FluSurv -NET\n▪>300 acute -care hospitals\n▪98 counties in 13 states\n▪In 9 of 10 HHS regions\n▪~10% of U.S. population\n▪Positive SARS -CoV-2 within 14 days of or \nduring hospitalization\n▪Screening or clinician -driven testing\n▪Clinical data: representative sample of \nCOVID -NET patientsCOVID -NET: A RESP -NET population -based hospitalization \nsurveillance platform\n2\nWeekly Population -Based Rates of COVID -19-Associated \nHospitalizations —COVID -NET, March 2020 –August 26,  \n2023\n020406080100120140\n3/7/2020\n5/7/2020\n7/7/2020\n9/7/2020\n11/7/2020\n1/7/2021\n3/7/2021\n5/7/2021\n7/7/2021\n9/7/2021\n11/7/2021\n1/7/2022\n3/7/2022\n5/7/2022\n7/7/2022\n9/7/2022\n11/7/2022\n1/7/2023\n3/7/2023\n5/7/2023\n7/7/2023Rate per 100,000 population\nWeek Ending DateMarch 1, 2020 –August 26, 2023\n<6 months 6 months –4 years 5–11 years 12–17 years\n18–49 years 50–64 years 65–74 years ≥75 years020406080100120140Rate per 100,000 population\nWeek Ending DateJanuary 1 –August 26, 2023\nGray boxes indicate potential reporting delays. Interpretation of trends should be excluded from these weeks. Rates highest in ≥75 years, followed by \ninfants <6 months and adults 65 –74 years\n3\nEpidemiology of COVID -19–associated \nhospitalization among children\n01020304050607080Rate per 100,000 population\nWeek Ending Date\n<6 months 6 months –4 years 5–11 years 12–17 years\nGray boxes indicate potential reporting delays. Interpretation of trends should be excluded from these weeks. Weekly Population -Based Rates of COVID -19-Associated \nHospitalizations among Infants, Children, and Adolescents \n≤17 Years —COVID -NET, March 2020 –August 26, 2023\n5\nGray boxes indicate potential reporting delays. Interpretation of trends should be excluded from these weeks. 02468101214161820\n3/7/2020 6/7/2020 9/7/2020 12/7/2020 3/7/2021 6/7/2021 9/7/2021 12/7/2021 3/7/2022 6/7/2022 9/7/2022 12/7/2022 3/7/2023 6/7/2023Rate per 100,000 population\nWeek Ending Date\n6-23 months 2-4 years 5–11 years 12–17 yearsFocus on 6 months -17 years of ageWeekly COVID -19-Associated Hospitalization Rates among \nInfants, Children and Adolescents Ages 6 months –≤17 Years \n—COVID -NET, March 2020 –August 26, 2023\n6\nPercent of COVID -19-Associated Hospitalizations with Underlying \nMedical Conditions among Children and Adolescents Ages 5 –17 Years \nby Age Group —COVID -NET, January –June 2023\nData are limited to hospitalizations where COVID -19 is a likely primary reason for admission. Figure displays underlying medical conditions present in ≥5% in ≥1 age group.•54% of hospitalized \ninfants, children, and \nadolescents ages \n≤17 years have no\nunderlying medical \nconditions .\n•Hospitalizations \nchildren and \nadolescents ages ≥5 \nyears are more \nlikely to have \nunderlying medical \nconditions relative \nto children and \ninfants ages ≤4 \nyears.0510152025303540\n<6 months 6–<2 years 2–4 years 5–11 years 12–17 yearsWeighted % of COVID -19 associated \nhospitalizations\nPrematurity Asthma\nNeurologic disorders Obesity\nImmunocompromising condition Cardiovascular disease\nFeeding tube dependence Chronic lung disease, not including asthma\nBlood disorders Chronic metabolic diseases, including diabetes34% with no \nunderlying \nconditions59% with no \nunderlying \nconditions42% with no \nunderlying \nconditions23% with no \nunderlying \nconditions75% with no \nunderlying \nconditions\n7\n050100150200250\n10/9/2021 1/9/2022 4/9/2022 7/9/2022Rate per 100,000 population\nWeek Ending Date\n≤4 years (COVID -19) ≤4 years (Influenza)\n5–11 years (COVID -19) 5–11 years (Influenza)\n12–17 years (COVID -19) 12–17 years (Influenza)050100150200250\n10/8/2022 11/26/2022 1/14/2023 3/4/2023 4/22/2023 6/10/2023Rate per 100,000 population\nWeek Ending Date\n≤4 years (COVID -19) ≤4 years (Influenza)\n5–11 years (COVID -19) 5–11 years (Influenza)\n12–17 years (COVID -19) 12–17 years (Influenza)Cumulative Weekly Rates of COVID -19-and Influenza -Associated \nHospitalizations among Infants, Children, and Adolescents Ages \n≤17 Years —COVID -NET and FluSurv -NET*, October 2021 —July 2023\nOctober 2022 –July 2023 October 2021 –September 2022\n* Influenza Hospitalization Surveillance Network. Seasonal FluSurv -NET surveillance was extended into June for the 2021 -2022 season. Surveillance ended on April 30, 2023, for the 2022 –2023 \nseason. Hospitalization rates are among those with laboratory -confirmed influenza and SARS -CoV-2 and are not adjusted for likely reason for admission. 8\n212726 2532\n1619\n17 1723\n05101520253035\n<6 months 6 months –<2 years 2–4 years 5–11 years 12–17 yearsPercent of Hospitalizations\nCOVID-19 InfluenzaPercent of COVID -19-and Influenza -Associated Hospitalizations \nwith ICU Admission among Infants, Children, and Adolescents \nby Age Group —COVID -NET and FluSurv -NET*, October 2022 –\nApril 2023\n•Influenza Hospitalization Surveillance Network\nLimited to COVID -NET hospitalizations with COVID -19-related illness as likely reason for admission9\nVaccination Status by Age Group among Infants, Children and \nAdolescents Ages ≤17 Years Hospitalized for COVID -19 —\nCOVID -NET, January –June 2023\nData are limited to hospitalizations where COVID -19 is a likely primary reason for admission. Unvaccinated : No recorded doses of COVID -19 vaccine. Vaccinated, but no bivalent booster : \nCompleted a primary series with or without ≥1 booster dose but did not receive an updated bivalent booster dose. Updated bivalent booster : Received updated bivalent booster dose. \nPartially vaccinated : Received at least one dose of COVID -19 but was not considered fully vaccinated at the time of a positive SARS -CoV-2 test. Pers ons with unknown vaccination status \nare excluded. 86\n63\n268\n28\n634 6\n0%10%20%30%40%50%60%70%80%90%100%\n6 months –4 years 5–11 years 12–17 yearsPercent of COVID -19-asssoicated \nhospitalizations\nUnvaccinated Vaccinated, but no bivalent booster Updated bivalent booster Partially vaccinated\n10\nEpidemiology of COVID -19–associated \nhospitalizations among adults\nWeekly Population -Based Rates of COVID -19-Associated \nHospitalizations among Adults Ages ≥18 Years —COVID -NET, \nMarch 2020 –August 2023\n020406080100120140Rate per 100,000 population\nWeek Ending DateMarch 1, 2020 –August 26, 2023 (entire pandemic period)\n18–49 years 50–64 years 65–74 years ≥75 years020406080100120140Rate per 100,000 population\nWeek Ending DateJanuary 1 –August 26, 2023\nGray boxes indicate potential reporting delays. Interpretation of trends should be excluded from these weeks. 12\nUnderlying Medical Conditions among Adults Ages ≥18 Years Hospitalized \nfor COVID -19, by Age Group  —COVID -NET, January –June 2023\n274966\n2238 39\n31\n263640 41\n29\n23\n17\n102133 33\n141716\n814\n614\n7525 413 1224\n92528\n010203040506070\n18–49 years 50–64 years ≥65 yearsWeighted % of hospitalizations\nCardiovascular disease Diabetes\nNeurologic disorders Obesity\nAsthma Chronic lung disease, not including asthma\nImmunocompromising condition Gastrointenstinal/liver Disease\nBlood disorders Autoimmune/inflammatory disease\nChronic metabolic disease, not including diabetes Renal disease\nData are limited to hospitalizations where COVID -19 is a likely primary reason for admission.18–49 years:\n58% with ≥3 underlying \nconditions50–64 years:\n72% with ≥3 underlying \nconditions≥65 years:\n81% with ≥3 underlying \nconditions\n13\nCumulative Weekly Rates of COVID -19-and Influenza -\nAssociated Hospitalizations among Adults Ages ≥18 Years —\nCOVID -NET and FluSurv -NET*, October 2022 –July 2023\n050100150200250\n10/8/2022 12/8/2022 2/8/2023 4/8/2023 6/8/2023Rate per 100,000 population\nWeek Ending DateAdults ages 18 –64 years\n18–49 years (COVID -19) 18–49 years (Influenza)\n50–64 years (COVID -19) 50–64 years (Influenza)\n* Influenza Hospitalization Surveillance Network. Seasonal FluSurv -NET surveillance ended on April 30, 2023, for the 2022 –2023 season.05001000150020002500\n10/8/2022 12/8/2022 2/8/2023 4/8/2023 6/8/2023Rate per 100,000 population\nWeek Ending DateAdults ages ≥65 years\n65–74 years (COVID -19) 65–74 years (Influenza)\n75–84 years (COVID -19) 75–84 years (Influenza)\n≥85 years (COVID -19) ≥85 years (Influenza)\n14\nPercent of COVID -19-and Influenza -Associated Hospitalizations with \nICU admission among Adults by Age Group —COVID -NET and FluSurv -\nNET*, 13 States, October 2022 –April 2023\n•Influenza Hospitalization Surveillance Network\nLimited to COVID -NET hospitalizations with COVID -19-related illness as likely reason for admission1922\n18\n711141817\n12\n8\n0510152025\n18–49 years 50–64 years 65–74 years 75–84 years ≥85 yearsPercent of  COVID -19-and\nInfluenza -associated Hospitalizations\nCOVID-19 Influenza\n15\nPercent of COVID -19-and Influenza -Associated Hospitalizations with in -\nhospital death among Adults by Age Group —COVID -NET and FluSurv -\nNET*, 13 States, October 2022 –April 2023\n2.14.06.4\n4.9\n4.1\n0.72.93.14.34.6\n01234567\n18–49 years 50–64 years 65–74 years 75–84 years ≥85 yearsPercent of  COVID -19-and\nInfluenza -associated Hospitalizations\nCOVID-19 Influenza\n•Influenza Hospitalization Surveillance Network\nLimited to COVID -NET hospitalizations with COVID -19-related illness as likely reason for admission16\nVaccination Status by Age Group among Non -Pregnant \nAdults Ages ≥18 Years Hospitalized for COVID -19 —COVID -\nNET, January –June 2023\nData are limited to hospitalizations where COVID -19 is a likely primary reason for admission. Unvaccinated : No recorded doses of COVID -19 vaccine. Vaccinated, but no bivalent booster : \nCompleted a primary series with or without ≥1 booster dose but did not receive an updated bivalent booster dose. Updated bivalent booster : Received updated bivalent booster dose. \nPartially vaccinated : Received at least one dose of COVID -19 but was not considered fully vaccinated at the time of a positive SARS -CoV-2 test. Pers ons with unknown vaccination status \nare excluded. 3526171153\n58\n61698 131919\n0%10%20%30%40%50%60%70%80%90%100%\n18–49 years 50–64 years 65–74 years ≥75 yearsPercent of COVID -19-associated \nhospitalizations\nUnvaccinated Vaccinated, but no bivalent booster Updated bivalent booster Partially vaccinated\n17\n▪Hospitalization rates increased in all age groups since mid -July\n▪Hospitalization rates highest in older adults and infants <6 months\n▪Most children <5 years hospitalized with COVID -19 illness have no underlying medical \nconditions\n–A higher proportion of hospitalized children and adolescents 5 -17 years have \nunderlying medical conditions\n–Most hospitalized adults have multiple underlying medical conditions\n▪COVID -19 continues to cause severe illness; clinical outcomes generally comparable to \ninfluenza -associated hospitalizations\n▪Most children and adults hospitalized for COVID -19 since January 2023 had not \nreceived an updated bivalent boosterCOVID -19-associated hospitalizations\n18\nCoronavirus and Other Respiratory \nViruses Division\nChris Taylor\nKadam Patel\nMeredith McMorrow\nInfluenza Division\nShikha Garg\nCatherine Bozio\nAlissa O’Halloran\nDawud UjamaaRESP -NET Site investigators and staffAcknowledgements\nFor more information, contact CDC\n1-800 -CDC -INFO (232 -4636)\nTTY:  1 -888 -232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention.\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.", "summary": "Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. COVID -19–Associated Hospitalizations among  Infants, Children and Adults —COVID -NET, January – August 2023 ACIP , September 12, 2023 Fiona P . Havers, MD, MHS Team…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-september-12-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-09-12/03-COVID-Havers-508.pdf", "doc_date": "2023-09-12", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 20}
{"title": "04 COVID Saydah 508", "content": "National Center for Immunization & Respiratory Diseases\nUpdate: E pidemiologic \nCharacteristics of Long COVID\nSharon Saydah, PhD, MHS, CDR USPHS\nCoronaviruses and Other Respiratory Viruses Division, \nEpidemiology Branch\nPost COVID Conditions -Longer Term Sequelae Team Lead\nSeptember 12, 2023 \nA general framework for Post -COVID Conditions\nConditions frequently overlap\nPatients may experience any combination\n*ME/CFS: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome\n** MIS -C: Multisystem Inflammatory Syndrome in ChildrenWide range of physical and mental health consequences continue or \ndevelop at least 4 weeks after initial COVID -19 or SARS -CoV-2 infection\nGeneral consequences of illness and \nhospitalization\n•Post ICU syndrome\n•Other complications of treatment \nor illnessPost acute sequelae of SARS -CoV-2 \ninfection\n•System specific pathology (e.g. \nlung fibrosis, stroke)\n•Clinicall y significant symptoms \nwith unclear pathology (e.g. \nME/CFS* -like, dysautonomia) \n•On-going symptoms following \nMIS-C**\nLong COVID commonly used term for Post -COVID \nConditions\nEstimating the Occurrence of Post -COVID Conditions\nPrevalence of on -going symptoms lasting at least 3 months \nafter COVID -19 by age, regardless of COVID status: U.S. \n10.81.96.89\n7.4\n4.2\n0.2 0.30.82.74.7\n3.8\n2.3\n0.01.02.03.04.05.06.07.08.09.010.0\n0 - 5 years 6 - 11 years 12 - 17 years 18-34 years 35-49 years 50-64 years ≥ 65 yearsPrevalence (%)\nEver Current\nUNPUBLISHED CDC DATA –Preliminary  estimates from 2022 National Health Interview SurveyNationally representative of non -institutional population in the U.S., s tatistical software was used to account for NHIS’s complex sampling design.\nTrends of Long COVID and significant activity limitations among \nadults -United States, June 1 –13, 2022, to June 7 –19, 2023\nThe prevalence of Long COVID \n(currently reporting symptoms lasting ≥ \n3 months) among non -institutionalized \nadults:\n•Decreased from June 2022 to January \n2023\n•Remained unchanged through June \n2023Almost 1 in 4 adults with Long COVID \nreport significant activity limitations\nLong COVID and Significant Activity Limitation Among Adults, by Age —United States, June 1 –13, 2022, to June 7 –19, 2023 | \nMMWR (cdc.gov)\n\nUsing electronic health records and comparing patients with COVID -19 to those \nwithout evidence of COVID -19:\n•Among children and adolescents, increased risk of four symptoms and eight \nconditions  31–365 days following COVID -19 1,2\n–Associated with an increased risk of heart conditions, kidney failure, blood clots, \ndiabetes, fatigue, smell and taste disorders, neurological conditions\n•Among adults, 1 in 5 COVID -19 survivors may have a health condition associated \nwith previous COVID -19 in the 31 –365 days following COVID -19 3\n–Associated with an increased risk of cardiovascular events, kidney disease, \nrespiratory conditions, diabetes, and neurological conditions 2,4,5,6SARS -CoV-2 infection associated with diagnosis of \nincident conditions\n1) Post –COVID -19 Symptoms and Conditions Among Children and Adolescents —United States, March 1, 2020 –January 31, 2022 | MMWR ( cdc.gov)\n2) Hernandez -Romieu AC et al. JAMA Netw Open. 2022; 5(2 )\n3) Bull-Otterson et al. Post -COVID Conditions Among Adult COVID -19 Survivors Aged 18 –64 and ≥65 Years –United States, March 2020 –November 2021 . MMWR May 27, 2022. \n4)Post –acute sequalae of COVID -19 and cardiac outcomes in U. S. military members -ScienceDirect\n5) Risk of persistent and new clinical sequelae among adults aged 65 years and older during the post -acute phase of SARS -CoV-2 infe ction: retrospective cohort study | The BMJ\n6) Long -term neurologic outcomes of COVID -19 | Nature Medicine\nIn a prospective study of adults testing positive and negative for COVID -19:\n•Following acute -COVID -like illness among adults, on -going symptoms decrease after \n3 months, but 16% continue to experience on -going symptoms at 12 months\n•Many adults reported new emerging or re -emerging symptoms at 6, 9, and 12 \nmonths following acute COVID -like illness\n•Symptoms were not unique to SARS -CoV-2 infection\nIn the Veterans Affairs patient population:\n•Post -COVID Conditions decreased 90 days after acute COVID -19, with increased risk \nof new conditions continuing for up to 2 years.Post -COVID Conditions symptoms and duration\nPrevalence of Symptoms ≤12 Months After Acute Illness, by COVID -19 Testing Status Among Adults —United States, \nDecember 2020 –March 2023 | MMWR (cdc.gov)\nPostacute sequelae of COVID -19 at 2 years | Nature Medicine\n•Female sex\n•Older age (sometimes)\n–Adolescents compared to younger children\n–Middle -aged adults compared to younger and older adults for symptoms\n–Older adults compared to younger adults for incident conditions\n•Severity of COVID -19 illness\n•Underlying health conditions prior to COVID -19\n•Lower socio -economic status\n•Did not get COVID -19 vaccineGroups associated with a higher likelihood of \ndeveloping Long COVID\nMaglietta G et al. Prognostic Factors for Post -COVID -19 Syndrome: A Systematic Review and Meta -Analysis. JCM \n2022\nSocioeconomic inequalities of Long COVID -UK.  Shabnam et al. 2023 (sagepub.com)\nHastie. et al. Outcomes among confirmed cases and matched comparison group in the Long COVID in Scotland \nStudy. Nature 2022\nEpidemiology of Long Coronavirus Disease in US Adults | Clinical Infectious Diseases | Oxford Academic (oup.com)\nFrontiers | Hospital admission and vaccination as predictive factors of long COVID -19 symptoms (frontiersin.org)\nCOVID -19 Vaccines and Post -COVID Conditions\nCOVID -19 vaccination \n(1 or 2 doses) reduces \nPost -COVID Conditions \ncompared to no \nvaccination among \nthose with SARS -CoV-2 \ninfection\nProtective effect of COVID -19 vaccination against \nlong COVID syndrome: A systematic review and \nmeta -analysis -ScienceDirect\n•COVID -19 cases diagnosed from \nMarch 2021 –February 2022, \nfollowed through August 2022\n•161,531 with COVID vaccination \nprior to infection matched 1:1 \nwith patients without \nvaccinationAssociations of prior \nCOVID -19 vaccination and \nrisk of PCC categories 6 \nmonths following SARS -\nCoV-2 infection, by age \ngroup: Mar 2021 -Feb 2022\nUNPUBLISHED DATA\nVaccine Safety Datalink Adjusted RR (95% CI)\nCOVID -19 mRNA vaccination associated with reduced occurrence of Post COVID \nConditions following SARS -CoV-2 infection in a US cohort of adult essential workers, \nJune 2021 --September 2022\nUnpublished data from the HEROES/RECOVER cohort. HEROES Protocol ; RECOVER ProtocolTotal (N =936)Unvaccinated\n(n= 157)Vaccinated 2 doses (≥ 14 days)\n(n= 301)Vaccinated 3 doses (≥ 7 days) \n(n=478)\nN (Col %) N (Row %) N (Row%) aOR (95% CI)a N (Row%) aOR (95% CI)a\n1 or more symptoms 221 (23.6) 42 (19.0) 74 (33.5) 1.00 (0.80 -1.27) 105 (47.5) 0.84 (0.67 -1.06)\n2 or more symptoms 158 (16.9) 27 (17.1) 62 (39.2) 1.22 (0.94 -1.59) 69 (43.7) 0.76 (0.58 -0.99)\nCardiovascular symptoms 107 (11.4) 19 (17.8) 44 (41.1) 1.32 (0.98 -1.78) 44 (41.1) 0.73 (0.54 -0.99)\nGastrointestinal \nsymptoms 46 (4.9) 12 (26.1) 17 (37.0) 1.04 (0.67 -1.61) 17 (37.0) 0.60 (0.39 -0.94)\nGeneral symptoms 142 (15.2) 26 (18.3) 58 (40.8) 1.22 (0.94 -1.60) 58 (40.8) 0.81 (0.62 -1.05)\nNeurological symptoms 128 (13.7) 26 (20.3) 44 (34.4) 1.08 (0.81 -1.43) 58 (45.3) 0.75 (0.57 -0.99)\nOther symptoms 80 (8.5) 19 (23.8) 29 (36.3) 1.08 (0.77 -1.51) 32 (40.0) 0.68 (0.48 -0.95)\nCOVID -19 mRNA vaccination associated with reduced occurrence of \nPost COVID Conditions following Omicron SARS -CoV-2 infection in a US \ncohort of children aged 5 -17 years, July 2021 --September 2022\nUnvaccinated, \n148 (row %)Vaccinated1,\n474 (row %)OR (95% CI) Adjusted OR2\n(95% CI)\n1 or more PCC symptoms 12 (43) 16 (57) 0.63 (0.43 -0.93) 0.66 (0.43 -0.99)\n2 or more PCC symptoms 11 (52) 10 (48) 0.52 (0.34 -0.81) 0.52 (0.32 -0.83)\nRespiratory PCC symptoms 10 (53) 9 (47) 0.52 (0.33 -0.82) 0.53 (0.32 -0.86)\nNon -Respiratory PCC symptoms 10 (42) 14 (58) 0.64 (0.42 -0.98) 0.70 (0.45 -1.10)\nPCC Impact on function 9 (56) 7 (44) 0.51 (0.22 -1.15) 0.62 (0.21 -1.83)\nUnpublished data from the PROTECT cohort. PROTECT Protocol\nSummary\n•Post -COVID Conditions are common following SARS -CoV-2 infection, decrease \nwith time since infection, and has decreased since the start of the pandemic\n•Symptoms and conditions associated with Post -COVID Conditions are not \nunique to having had SARS -CoV-2 infection\n•Post -COVID Conditions are associated with increased health care utilization and \nsignificant activity limitations\n•Accumulating evidence that COVID -19 vaccination reduces Post -COVID \nConditions among both children and adultsImportant take home messages\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the \nofficial position of the Centers for Disease Control and Prevention.\nFor more information:\nSharon Saydah, PhD, MHS zle0@cdc.govQuestions?", "summary": "National Center for Immunization & Respiratory Diseases Update: E pidemiologic  Characteristics of Long COVID Sharon Saydah, PhD, MHS, CDR USPHS Coronaviruses and Other Respiratory Viruses Division,  Epidemiology Branch Post COVID Conditions -Longer Term Sequelae Team Lead September 12, 2023  A general framework for Post -COVID Conditions Conditions frequently overlap Patients may experience any combination *ME/CFS: Myalgic Encephalomyelitis/Chronic Fatigue Syndrome ** MIS -C: Multisystem…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-september-12-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-09-12/04-COVID-Saydah-508.pdf", "doc_date": "2023-09-12", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 16}
{"title": "05 COVID Link Gelles 508", "content": "1\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nUpdates to COVID -19 vaccine effectiveness (VE) in \nthe U.S\nSeptember 12, 2023\nRuth Link -Gelles, PhD, MPH\nCDR, US Public Health Service\nCOVID -19 Vaccine Effectiveness Program Lead\nCenters for Disease Control and Prevention\n2▪Included today:\n–VE against emergency department/urgent care encounters in young children\n–VE against emergency department/urgent care encounters in older children, adolescents, and adults\n–VE against hospitalization and critical illness in adults\n▪Note: updates in this presentation are meant to complement results of the GRADE \npresentationOrganization of presentation\n3▪High rates of infection -induced immunity \nby July –August 2022.*\n▪VE findings should be interpreted as the \nincremental benefit provided by COVID -19 \nvaccination in a population with a high \nprevalence of infection -induced immunity.Context for interpreting VE across age groups\n* https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2023 -06-21-23/03 -COVID -Jones -508.pdf ; data on children aged 6 months –17 years is from cross -sectional blood specimens collected by \ncommercial laboratories. Data on persons aged ≥16 years is from a longitudinal, national cohort of >70,000 blood donors.Age group% with infection -induced \nimmunity\n6-11 month 66%\n12-23 months 74%\n2-4 years 83%\n5-11 years 88%\n12-17 years 86%\n16-29 years 83%\n30-49 years 78%\n50-64 years 68%\n≥65 years 48%\n4\nVaccine effectiveness in young children\nVISION Network (emergency department/urgent care encounters)\nUpdates based on analyses in recent MMWR:\n•Link -Gelles R, Ciesla AA, Rowley EA, et al. Effectiveness of Monovalent and Bivalent mRNA Vaccines in Preventing \nCOVID -19–Associated Emergency Department and Urgent Care Encounters Among Children Aged 6 Months –5 \nYears —VISION Network, United States, July 2022 –June 2023. MMWR Morb Mortal Wkly Rep 2023;72:886 –892. \nDOI: http://dx.doi.org/10.15585/mmwr.mm7233a2\n55VISION Multi -Site Network of Electronic Health Records\n▪Design: Test-negative case -control\n▪Population: Immunocompetent children \naged 6 months –4 or 5 years visiting a \nparticipating emergency department or \nurgent care (ED/UC) with COVID -19-like \nillness (CLI) with a SARS -CoV -2 NAAT test \nresult within 14 days before or 72 hours \nafter encounter\n−Cases : CLI with positive NAAT for SARS -CoV -2\n−Controls : CLI with negative NAAT for SARS -CoV -2\n▪Vaccination data: Documented by electronic health records and state \nand city registries\n▪Dates of analysis: July 2022 –August 2023\n66VISION: Estimates of VE for original monovalent Moderna primary series vaccine \n(children aged 6 months –5 years) against ED/UC encounters , July 4, 2022 –August 9, \n2023*\nVaccination status (months since last dose) Total testsSARS -CoV -2\npositive, N (%)Median interval since \nlast dose, days (IQR)Adjusted\nVE (95% CI)\nModerna , 1 dose ( partial series; ages 6mo –5years)\nJuly 4, 2022 –June 17, 2023\nUnvaccinated 90,737 4,966 (5.5) NA Ref\n1 (original) monovalent dose (≥14 days) 1,053 47 (4.5) 66 (30 –127) 23 (−3 to 43)\nModerna , 2 doses ( complete series; ages 6mo –5years)\nAugust 1, 2022 –June 17, 2023\nUnvaccinated 85,746 4,061 (4.7) NA Ref\n2 (original) monovalent doses (≥14 days) 3,736 98 (2.6) 105 (64 –169) 31 (15 to 44)\n2 (original) monovalent doses (14 -59 days) 811 23 (2.8) 38 (26 –49) 46 (17 to 64)\n2 (original) monovalent doses (≥60 days) 2,925 75 (2.6) 124 (91 –193) 24 (4 to 40)\n-40 -20 0 20 40 60 80 100\nVaccine Effectiveness (%)\n* Different analysis periods were used for each product and dose number because vaccinated children became eligible to be inc luded 14 days after the dose at different times: 1 \ndose of Moderna and Pfizer -BioNTech on July 4, 2022; 2 doses of Pfizer -BioNTech on July 25, 2022; 2 doses of Moderna on August 1 , 2022; 3 doses of Pfizer -BioNTech on \nSeptember 19, 2022; bivalent doses on December 24, 2022.\n77VISION: Estimates of VE for original monovalent Pfizer -BioNTech primary series vaccine (children \naged 6 months –4 years) against ED/UC encounters , July 4, 2022 –June 17, 2023\nVaccination status (months since last dose) Total testsSARS -CoV -2\npositive, N (%)Median interval since \nlast dose, days (IQR)Adjusted\nVE (95% CI)\nPfizer , 1 dose ( partial series; ages 6mo –4 years)\nJuly 4, 2022 –June 17, 2023\nUnvaccinated 79,480 4,632 (5.8) NA Ref\n1 (original) monovalent dose (≥14 days) 1,640 78 (4.8) 60 (29 –112) 8 (−16 to 27)\nPfizer , 2 doses ( partial series; ages 6mo –4 years)\nJuly 25, 2022 –June 17, 2023\nUnvaccinated 75,965 3,990 (5.2) NA Ref\n2 (original) monovalent doses (≥14 days) 2,682 78 (2.9) 70 (41 –121) 34 (16 to 47)\n2 (original) monovalent doses (14 -59 days) 1,138 34 (3.0) 37 (25 –47) 44 (21 to 61)\n2 (original) monovalent doses (≥60 days) 1,544 44 (2.9) 111 (82 –164) 23 (−5 to 43)\nPfizer , 3 doses ( complete series; ages 6mo –4 years)\nSeptember 19, 2022 –June 17, 2023\nUnvaccinated 66,847 2,992 (4.5) NA Ref\n3 (original) monovalent doses (≥14 days) 1,542 33 (2.1) 82 (43 –153) 38 (12 to 56)\n3 (original) monovalent doses (14 -59 days) 573 6 (1.1) 35 (26 –46) 71 (36 to 87)**\n3 (original) monovalent doses (≥60 days) 969 27 (2.8) 132 (89 –187) 16 (−24 to 43)**\n-40 -20 0 20 40 60 80 100\nVaccine Effectiveness (%)* Different analysis periods were used for each product and dose number because vaccinated children became eligible to be inc luded 14 days after the dose at different times: 1 dose of Moderna and \nPfizer -BioNTech on July 4, 2022; 2 doses of Pfizer -BioNTech on July 25, 2022; 2 doses of Moderna on August 1, 2022; 3 doses of P fizer -BioNTech on September 19, 2022; bivalent doses on December 24, \n2022.\n** This estimate is imprecise, which might be due to there being a relatively small number of persons in each level of vaccin ation or case status. This imprecision indicates that the actual VE could be \nsubstantially different from the point estimate shown, and estimates should therefore be interpreted with caution. Additional data accrual could increase precision and allow more precise interpretation.\n88VISION: Estimates of VE for ≥1bivalent vaccine (children aged 6 months –4 or 5 years) against ED/UC \nencounters , December 24, 2022 –June 17, 2023\nVaccination status (months since last dose) Total testsSARS -CoV -2\npositive, N (%)Median interval since \nlast dose, days (IQR)Adjusted\nVE (95% CI)\nRegardless of manufacturer, ≥1 bivalent dose (ages 6mo –5years)\nUnvaccinated 34,582 1,505 (4.3) NA Ref\n≥1 bivalent dose (≥14 days) 458 8 (1.8) 66 (39 –103) 61 (22 to 83)**\n-60 -40 -20 0 20 40 60 80 100\nVaccine Effectiveness (%)\n*This estimate was calculated using unadjusted exact methods due to the small number of vaccinated case -patients. Five vaccinate d case -patients received bivalent Pfizer -BioNTech doses and three received Moderna \ndoses; vaccinated control -patients included those who received both bivalent Moderna (126) and Pfizer -BioNTech (324) doses.\nThis estimate is imprecise, which might be due to there being a relatively small number of persons in each level of vaccinati on or case status. This imprecision indicates that the actual VE could be substantially different \nfrom the point estimate shown, and estimates should therefore be interpreted with caution. Additional data accrual could incr ease precision and allow more precise interpretation.\nChildren included in the bivalent analysis were either unvaccinated (received 0 COVID -19 vaccine doses) or had received ≥1 bival ent vaccine dose from either manufacturer. Among those who received a bivalent \nvaccine dose, any combination of original monovalent and bivalent doses was included, but at minimum children had to have rec eived 2 Moderna doses or 3 Pfizer -BioNTech doses (i.e., a complete primary series). \n9▪1 dose of original monovalent Moderna or Pfizer -BioNTech vaccines did not provide \nsignificant protection\n▪2 doses of either product (and 3 doses of Pfizer -BioNTech) provided protection against \nED/UC and hospitalization, though waning was evident (similar to older children and \nadults)\n▪A bivalent dose provided protection, though sample size was limited.\n▪Median interval since receipt of the most recent dose among children who had not \ncompleted their primary series was longer than expected based on the recommended \ndosing intervals →some children not completing primary seriesConclusions: Vaccine effectiveness in young children\n10\nUpdates to bivalent vaccine effectiveness\nVISION Network\nUpdates based on analyses in recent MMWRs:\nLink -Gelles, et al. Estimates of Bivalent mRNA Vaccine Durability in Preventing COVID -19–Associated Hospitalization \nand Critical Illness Among Adults with and Without Immunocompromising Conditions —VISION Network, September \n2022 –April 2023. https://www.cdc.gov/mmwr/volumes/72/wr/mm7221a3.htm\nIVY Network\nUpdates based on analyses in recent MMWR:\n•DeCuir, Surie, et al. MMWR. Effectiveness of Monovalent mRNA COVID -19 Vaccination in Preventing COVID -19–\nAssociated Invasive Mechanical Ventilation and Death Among Immunocompetent Adults During the Omicron \nVariant Period —IVY Network, 19 U.S. States, February 1, 2022 –January 31, 2023. \nhttps://www.cdc.gov/mmwr/volumes/72/wr/mm7217a3.htm\n1111VISION Multi -State Network of Electronic Health Records\n▪Design: Test-negative case -control\n▪Population: Persons admitted to a \nparticipating emergency department, \nurgent care, or hospital with COVID -19-like \nillness (CLI) with a SARS -CoV -2 NAAT test \nresult within 14 days before or 72 hours \nafter encounter or admission\n−Cases : CLI with positive NAAT for SARS -CoV -2\n−Controls : CLI with negative NAAT for SARS -CoV -2\n▪Vaccination data: Documented by electronic health records and state \nand city registries\n▪Dates of analysis: September 2022 –August 2023\n1212VISION: Absolute VE of original monovalent and bivalent booster doses \nagainst ED/UC encounters among immuno competent persons, by age \ngroup –September 2022 –August 2023\nVE estimates adjusted for age, sex, race and ethnicity, geographic region, and calendar time. CDC unpublished datamRNA Dosage PatternTotal\ntestsSARS -CoV -2-\ntest -positive,\nN (%)Median interval\nsince last dose,\ndays (IQR)Adjusted VE (95% CI)\nUnvaccinated\n5-17 years 41,910 1,446 (4) -- Ref\n18-64 years 90,349 8,201 (9) -- Ref\n≥65 years 17,108 2,453 (14) -- Ref\nOriginal monovalent doses only\n5-17 years 28,369 1,092 (4) 334 (253 -439) 7 (-1 to 15)\n18-64 years 14,9267 14,270 (10) 441 (334 -564) 2 (-1 to 5)\n≥65 years 69,989 8,538 (12) 383 (266 -531) 17 (12 to 21)\nBivalent booster, 7 -59 days earlier\n5-17 years 1,858 30 (2) 30 (18 -44) 63 (46 to 74)\n18-64 years 9,763 549 (6) 33 (21 -46) 56 (52 to 60)\n≥65 years 1,1826 970 (8) 35 (21 -48) 59 (55 to 62)\nBivalent booster, 60 -119 days earlier\n5-17 years 1,268 37 (3) 89 (74 -105) 36 (10 to 54)\n18-64 years 9,558 682 (7) 86 (72 -102) 39 (34 to 44)\n≥65 years 12,753 1,255 (9) 87 (73 -102) 47(42 to 51)\n-20 0 20 40 60 80 100\nVaccine Effectiveness (%)\n1313VISION: Absolute VE of original monovalent and bivalent booster doses \nagainst hospitalization among immuno competent adults, by age group –\nSeptember 2022 –August 2023\nVE estimates adjusted for age, sex, race and ethnicity, geographic region, and calendar time. Updated from: Link -Gelles et al., MMWR, https://www.cdc.gov/mmwr/volumes/72/wr/mm7221a3.htm\n* These estimates are imprecise, which might be due to there being a relatively small number of persons in each level of vacc ination or case status. This imprecision indicates that the actual VE \ncould be substantially different from the point estimate shown, and estimates should therefore be interpreted with caution. A dditional data accrual could increase precision and allow more precise \ninterpretation.mRNA Dosage PatternTotal\ntestsSARS -CoV -2-\ntest -positive,\nN (%)Median interval\nsince last dose,\ndays (IQR)Adjusted VE\n(95% CI)\n18-64 years\nUnvaccinated (ref) 13,089 803 (6) -- Ref\nOriginal monovalent doses only 19,799 1,129 (6) 455 (333 -575) 15 (6 to 23)\nBivalent booster, 7 -59 days earlier 1,208 45 (4) 33 (21 -45) 61 (46 to 71)\nBivalent booster, 60 -119 days earlier 1,248 87 (7) 87 (73 -102) 15 (-8 to 33)\nBivalent booster, 120 -179 days earlier 1,075 59 (6) 147 (134 -163) -1 (-35 to 24)*\n≥65 years\nUnvaccinated (ref) 12,015 1,688 (14) -- Ref\nOriginal monovalent doses only 37,001 4,216 (11) 402 (288 -555) 25 (20 -30)\nBivalent booster, 7 -59 days earlier 4,607 328 (7) 35 (21 -48) 67 (62 -71)\nBivalent booster, 60 -119 days earlier 5,252 490 (9) 88 (73 -104) 53 (48 -58)\nBivalent booster, 120 -179 days earlier 4,482 415 (9) 149 (134 -164) 28 (18 -36)\n-40 -20 0 20 40 60 80 100\nVaccine Effectiveness (%)\n1414VISION: Absolute VE of original monovalent and bivalent booster doses \nagainst hospitalization and critical illness among immuno competent\nadults aged ≥18 years –September 2022 –August 2023\nCritical illness defined as admission to intensive care unit or death; case -patients were persons admitted to ICU or who experie nced death associated with COVID -19, and \ncontrol patients were persons hospitalized without COVID -19. VE estimates adjusted for age, sex, race and ethnicity, geographic region, and calendar time. Updated from: Link -\nGelles et al., MMWR, https://www.cdc.gov/mmwr/volumes/72/wr/mm7221a3.htmmRNA Dosage PatternTotal\ntestsSARS -CoV -2-\ntest -positive,\nN (%)Median interval\nsince last dose,\ndays (IQR)Adjusted VE\n(95% CI)\nHospitalization\nUnvaccinated (ref) 25,104 2,491 (10) -- Ref\nOriginal monovalent doses only 56,800 5,345 (9) 420 (306 -563) 22 (17 -26)\nBivalent booster, 7 -59 days earlier 5,815 373 (6) 34 (21 -47) 65 (61 -69)\nBivalent booster, 60 -119 days earlier 6,500 577 (9) 87 (73 -103) 48 (42 -53)\nBivalent booster, 120 -179 days earlier 5,557 474 (9) 149 (134 -164) 22 (13 -30)\nCritical illness\nUnvaccinated (ref) 23,140 527 (2) -- Ref\nOriginal monovalent doses only 52,352 897 (2) 422 (306 -564) 32 (23 -40)\nBivalent booster, 7 -59 days earlier 5,504 62 (1) 34 (21 -47) 69 (59 -77)\nBivalent booster, 60 -119 days earlier 6,023 100 (2) 87 (73 -103) 50 (36 -60)\nBivalent booster, 120 -179 days earlier 5,144 61 (1) 149 (134 -164) 46 (28 -60)\n-20 0 20 40 60 80 100\nVaccine Effectiveness (%)\n1515VISION: Absolute VE of original monovalent and bivalent booster doses \nagainst hospitalization among adults ≥18 years, by immunocompromise \nstatus –September 2022 –August 2023\nVE estimates adjusted for age, sex, race and ethnicity, geographic region, and calendar time. Updated from: Link -Gelles et al., MMWR, \nhttps://www.cdc.gov/mmwr/volumes/72/wr/mm7221a3.htmmRNA Dosage PatternTotal\ntestsSARS -CoV -2-\ntest -positive,\nN (%)Median interval\nsince last dose,\ndays (IQR)Adjusted VE\n(95% CI)\nWithout immunocompromising conditions\nUnvaccinated (ref) 25,104 2,491 (10) -- Ref\nOriginal monovalent doses only 56,800 5,345 (9) 420 (306 -563) 22 (17 -26)\nBivalent booster, 7 -59 days earlier 5,815 373 (6) 34 (21 -47) 65 (61 -69)\nBivalent booster, 60 -119 days earlier 6,500 577 (9) 87 (73 -103) 48 (42 -53)\nBivalent booster, 120 -179 days earlier 5,557 474 (9) 149 (134 -164) 22 (13 -30)\nWith immunocompromising conditions\nUnvaccinated (ref) 5,044 440 (9) -- Ref\nOriginal monovalent doses only 16,937 1,575 (9) 397 (276 -539) 1 (-11-12)\nBivalent booster, 7 -59 days earlier 1,970 168 (9) 34 (20 -47) 31 (16 -43)\nBivalent booster, 60 -119 days earlier 2,336 172 (7) 88 (74 -104) 40 (27 -50)\nBivalent booster, 120 -179 days earlier 2,188 166 (8) 149 (134 -164) 12 (-7-28)\n-20 0 20 40 60 80 100\nVaccine Effectiveness (%)\n1616IVY Network —25 hospitals, 20 U.S. States\n▪Design : Prospective, case -control\n▪Population : Adults aged ≥18 years hospitalized with \nAcute respiratory illness (ARI)*\n–Cases: ARI and test positive for SARS -CoV-2 by NAAT or \nantigen test within 10 days of illness\n–Controls : ARI and test negative for SARS -CoV-2 and influenza \nby NAAT within 10 days of illness\n▪Vaccination data: Electronic medical records (EMR), \nstate and city registries, and self -report\n▪Specimens: Upper respiratory specimens obtained \nfor central RT -qPCR testing and sequencing\n▪Dates of analysis: September 2022 –May 2023\n*ARI is defined as presence of any one of the following: fever, cough, shortness of breath, chest imaging consistent with pne umo nia, hypoxemia\n1717IVY: Absolute VE against COVID -19 hospitalization among \nimmuno competent adults aged ≥18 years —September 8, 2022 –May \n31, 2023\nCase vaccination \nstatus, no. (%)Control \nvaccination \nstatus, no. (%)Median time\nsince last dose,\ndays (IQR)Adjusted VE*,\n% (95% CI)\n18–64 years N=927 N=1,680\nUnvaccinated 307 (33) 483 (29) -- Ref\nOriginal monovalent doses only 514 (55) 979 (58) 412 (297 –533) 20 (4 –34)\nBivalent booster dose, 7 –89 days earlier 48 (5) 123 (7) 54 (33 –71) 43 (16 –62) \nBivalent booster dose, 90 –179 days earlier 58 (6) 95 (6) 130 (110 –151) 17 (-28 to 46)** \n≥65 years N=1,556 N=1,971\nUnvaccinated 238 (15) 274 (14) -- Ref\nOriginal monovalent doses only 992 (64) 1108 (56) 385 (278 –510) 1 (-20 to 19)\nBivalent booster dose, 7 –89 days earlier 131 (8) 329 (17) 52 (29 –68) 53 (37 –66) \nBivalent booster dose, 90 –179 days earlier 195 (13) 260 (13) 130 (109 –151) 10 (-24 to 35)** \n*VE adjustments: Age, sex, race/ ethnicity, admission date (biweekly), and HHS region\n** These estimates are imprecise, which might be due to there being a relatively small number of persons in each level of vac cination or case status. This imprecision indicates that the \nactual VE could be substantially different from the point estimate shown, and estimates should therefore be interpreted with caution. Additional data accrual could increase precision and \nallow more precise interpretation.-40 -20 0 20 40 60 80 100\nVaccine Effectiveness (%)\n1818IVY: Absolute VE against COVID -19 hospitalization among adults \naged ≥18 years , by immunocompromise status —September 8, 2022 \n–May 31, 2023\nCase vaccination \nstatus, no. (%)Control \nvaccination \nstatus, no. (%)Median time\nsince last dose,\ndays (IQR)Adjusted VE*,\n% (95% CI)\nImmunocompetent n=2,483 n=3,651\nUnvaccinated 545 (22) 757 (21) -- Ref\nOriginal monovalent doses only 1506 (61) 2087 (57) 395 (286 –521) 10 (-4 to 21)\nBivalent booster dose, 7 –89 days earlier 179 (7) 452 (12) 53 (30 –69) 51 (37 –61)\nBivalent booster dose, 90 –179 days earlier 253 (10) 355 (10) 130 (109 –151) 12 (-12 to 31) \nImmunocompromised n=809 n=1,257\nUnvaccinated 132 (16) 182 (14) -- Ref\nOriginal monovalent doses only 543 (67) 767 (61) 374 (256 –504) 13 (-14 to 33)\nBivalent booster dose, 7 –89 days earlier 59 (7) 160 (13) 46 (26 –72) 55 (29 –71) \nBivalent booster dose, 90 –179 days earlier 75 (9) 148 (12) 126 (107 –152) 43 (7 –65)**\n-20 0 20 40 60 80 100\nVaccine Effectiveness (%) * VE adjustments: Age, sex, race /ethnicity, admission date (biweekly), and HHS region\n** These estimates are imprecise, which might be due to there being a relatively small number of persons in each level of vac cination or case status. This \nimprecision indicates that the actual VE could be substantially different from the point estimate shown, and estimates should therefore be interpreted with \ncaution. Additional data accrual could increase precision and allow more precise interpretation.\n19▪VE waning against hospitalization and ED/UC; more sustained protection against critical \nillness\n–Difficult to separate impact of time since vaccination from emergence of new variants\n▪Patterns are similar across age groups, though low uptake of bivalent doses in younger age \ngroups prevented assessment of waning beyond 4 months from the bivalent dose.\n▪Persons with immunocompromise may have reduced protection after COVID -19 vaccination, \ncompared with persons without immunocompromise. Historically, COVID -19 VE has been \nlower and waned more quickly for adults with immunocompromise compared to adults \nwithout immunocompromise. Trends in bivalent VE are less clear and additional data are \nneeded.\n▪VE findings should be interpreted as the incremental benefit provided by COVID -19 \nvaccination in a population with a high prevalence of infection -induced immunity.Conclusions: Updates to waning of bivalent vaccine \neffectiveness\n20CDC COVID -19 Vaccine Effectiveness \nand Policy Team\n▪Amadea Britton\n▪Allison Ciesla\n▪Monica Godfrey\n▪Eric Griggs\n▪Katherine Fleming -Dutra\n▪Dani Moulia\n▪Morgan Najdowski\n▪Erica OkwuaziVE platforms teams, including:\n▪Sarah Ball\n▪Angela Campbell\n▪Jennifer DeCuir\n▪Monica Dickerson\n▪Margaret Dunne\n▪Kiara Everett\n▪Shikha Garg\n▪Victoria Lazariu\n▪Patrick Mitchell\n▪Palak Patel\nAnd many more!!!Acknowledgements\n▪Heidi Moline\n▪Caitlin Ray\n▪Sarah Reese\n▪Elizabeth Rowley\n▪Regina Simeone\n▪Zach Smith\n▪Diya Surie\n▪Mark Tenforde\n▪Zack Weber\n▪Laura Zambrano▪Josephine Mak\n▪Amanda Payne\n▪Lauren Roper\n▪Laura Steinhardt\n▪Megan Wallace\n▪Ryan Wiegand\n21\nFor more information, contact CDC\n1-800 -CDC -INFO (232 -4636)\nTTY:  1 -888 -232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention.\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nQuestions?\n22\nBack -up\n23New Vaccine Surveillance Network (NVSN)\nDesign: active, prospective, population -based ARI surveillance network for pediatric viral \ninfections at 7 medical centers.\nStudy population: Children <18 years with ARI are enrolled year -round in the outpatient,\nED, and hospital settings. Healthy controls are enrolled in the outpatient setting (well\nchild visits).\n▪5794 children 6mos -4yrs with acute respiratory illness during July 1, 2022 —June 30, 2023\nData collection: Demographic and clinical data are collected through parent/guardian \ninterviews and medical chart reviews, and laboratory testing.  Vaccine status verified through \nstate immunization registries and primary care record review.\nNVSN COVID -19 Vaccine Effectiveness Methodology\n–Test-negative design. All enrolled children are tested for 8 respiratory viruses.\n–Cases = SARS -CoV-2 positive, controls = SARS -CoV-2 negative.\n–Regression models adjusted for study site, sex, race, and calendar time (week of enrollment). \n–Vaccine status was defined as 1) unvaccinated = received zero COVID -19 vaccine doses of any product, 2) one dose only = received \none COVID -19 vaccine dose of any product, or 3) two or more doses = received two or more COVID -19 vaccine doses of any \nproduct. Children within two weeks of vaccine receipt were excluded. \n2424New Vaccine Surveillance Network (NVSN): VE of any product \nagainst emergency department visits and hospitalization, \nchildren 6 months –4 years, July 2022 -June, 2023\nCase vaccination \nstatus (n=291)Control vaccination \nstatus (n=5,503)Median time\nsince last dose,\ndays (IQR)Adjusted VE*,\n% (95% CI)\nUnvaccinated 260 (89) 4,691 (85) NA\nVaccinated with ≥1 dose* 31 (11) 812 (15) Not calculated Not calculated\nOne dose 10 (3) 228 (4) 61 (31 -105) 30 (-36-64)**\nTwo doses 21 (7) 584 (11) 74 (42 -131) 40 (3 -63)**\n-40 -20 0 20 40 60 80 100\nVaccine Effectiveness (%)\n* Vaccine status was defined as 1) unvaccinated = received zero COVID -19 vaccine doses of any product, 2) one dose only = receiv ed one COVID -19 vaccine dose of any product, or 3) two \nor more doses = received two or more COVID -19 vaccine doses of any product. Children within two weeks of vaccine receipt were ex cluded. \n** These estimates are imprecise, which might be due to there being a relatively small number of persons in each level of vaccin ation or case status. This imprecision indicates that the actual \nVE could be substantially different from the point estimate shown, and estimates should therefore be interpreted with caution . Additional data accrual could increase precision and allow \nmore precise interpretation.\n2525IVY: Absolute VE against COVID -19 hospitalization among \nimmuno competent adults aged ≥18 years by SARS -CoV -2 \nsubvariant predominance —September 8, 2022 –May 31, 2023\nCase vaccination \nstatus, no. (%)Control \nvaccination status, \nno. (%)Median time\nsince last dose,\ndays (IQR)Adjusted VE*,\n% (95% CI)\nBA.4/5 (September 8 –November 26, 2022) n=688 n=989\nUnvaccinated 169 (25) 199 (20)\nOriginal monovalent doses only 479 (70) 692 (70) 311 (195 –403) 32 (12 –47)\nBivalent booster dose, 7 –89 days earlier 40 (6) 98 (10) 29 (16 -45) 68 (46 –81)\nBQ.1 (November 27, 2022 –January 17, 2023) n=622 n=1,080\nUnvaccinated 145 (23) 223 (21)\nOriginal monovalent doses only 399 (64) 617 (57) 388 (306 –517) 12 (-14 to 32)\nBivalent booster dose, 7 –89 days earlier 78 (13) 240 (22) 55 (37 -69) 54 (33 –68)\nXBB.1.5 (January 18 –May 31, 2023) n=1,148 n=1,529\nUnvaccinated 231 (20) 335 (22)\nOriginal monovalent doses only 628 (55) 778 (51) 464 (374 –593) -10 (-35 to 10)\nBivalent booster dose, 7 –89 days earlier 61 (5) 114 (7) 65 (46 –80) 33 (0 –54)**\nBivalent booster dose, 90 –179 days earlier 228 (20) 302 (20) 136 (116 –154) -7 (-41 to 19)**\n*VE adjustments: Age, sex, race /ethnicity, admission date (biweekly), and HHS region\n** These estimates are imprecise, which might be due to there being a relatively small number of persons in each level of vaccin ation or case status. This \nimprecision indicates that the actual VE could be substantially different from the point estimate shown, and estimates should therefore be interpreted with caution. \nAdditional data accrual could increase precision and allow more precise interpretation.-60 -40 -20 0 20 40 60 80 100\nVaccine Effectiveness (%)\n2626VISION: Absolute VE of original monovalent and bivalent booster doses \nagainst hospitalization and critical illness among immuno competent\nadults aged ≥18 years, during XBB predominance –January –July 2023\nCDC unpublished data. VE estimates adjusted for age, sex, race and ethnicity, geographic region, and calendar time.\nVariant predominance based on regional circulation: https://covid.cdc.gov/covid -data -tracker/#variant -proportions\n* These estimates are imprecise, which might be due to there being a relatively small number of persons in each level of vaccin ation or case status. This imprecision indicates that the actual VE could be substantially different \nfrom the point estimate shown, and estimates should therefore be interpreted with caution. Additional data accrual could incr ease precision and allow more precise interpretation.mRNA Dosage PatternTotal\ntestsSARS -CoV -2-\ntest -positive,\nN (%)Median interval\nsince last dose,\ndays (IQR)Adjusted VE\n(95% CI)\nHospitalization\nUnvaccinated (ref) 10,443 700 (7) -- Ref\nOriginal monovalent doses only 23,140 1,662 (7) 511 (411 -639) 13 (5 -22)\nBivalent booster, 7 -59 days earlier 701 33 (5) 38 (23 -49) 57 (38 -70)\nBivalent booster, 60 -119 days earlier 2,350 165 (7) 98 (83 -110) 42 (31 -52)\nBivalent booster, 120 -179 days earlier 5,067 434 (9) 150 (136 -165) 21 (9 -31)\nCritical illness\nUnvaccinated (ref) 9,890 147 (2) -- Ref\nOriginal monovalent doses only 21,751 273 (1) 512 (412 -640) 25 (7 -40)\nBivalent booster, 7 -59 days earlier 674 6 (1) 38 (23 -49) 58 (4 -82)*\nBivalent booster, 60 -119 days earlier 2,211 26 (1) 98 (83 -110) 49 (20 -67)\nBivalent booster, 120 -179 days earlier 4,690 57 (1) 150 (136 -165) 44 (22 -60)\n-20 0 20 40 60 80 100\nVaccine Effectiveness (%)\n2727VISION: Absolute VE of original monovalent and bivalent booster doses against \nhospitalization among immuno competent adults aged ≥18 years, by SARS -CoV -2 \nsubvariant predominance –September 2022 –August 2023\nCDC unpublished data. VE estimates adjusted for age, sex, race and ethnicity, geographic region, and calendar time.\nVariant predominance based on regional circulation: https://covid.cdc.gov/covid -data -tracker/#variant -proportionsmRNA Dosage PatternTotal\ntestsSARS -CoV -2-\ntest -positive,\nN (%)Median interval\nsince last dose,\ndays (IQR)Adjusted VE\n(95% CI)\nBA.4/BA.5 predominance (September 2022 –November 2022)\nUnvaccinated (ref) 5427 606 (11) -- Ref\nOriginal monovalent doses only 14521 1377 (10) 312 (183 -397) 28 (19 -35)\nBivalent booster, 7 -59 days earlier 1856 129 (7) 25 (15 -37) 58 (49 -66)\nBQ.1 predominance (December 2022 –January 2023)\nUnvaccinated (ref) 4,193 619 (15) -- Ref\nOriginal monovalent doses only 9,787 1,300 (13) 390 (296 -495) 28 (19 -35)\nBivalent booster, 7 -59 days earlier 1,870 133 (7) 41 (28 -51) 69 (62 -75)\nBivalent booster, 60 -119 days earlier 2,780 288 (10) 82 (71 -94) 52 (44 -59)\nXBB predominance (February 2023 –August 2023)\nUnvaccinated (ref) 10,443 700 (7) -- Ref\nOriginal monovalent doses only 23,140 1,662 (7) 511 (411 -639) 13 (5 -22)\nBivalent booster, 7 -59 days earlier 701 33 (5) 38 (23 -49) 57 (38 -70)\nBivalent booster, 60 -119 days earlier 2,350 165 (7) 98 (83 -110) 42 (31 -52)\nBivalent booster, 120 -179 days earlier 5,067 434 (9) 150 (136 -165) 21 (9 -31)\n-20 0 20 40 60 80 100\nVaccine Effectiveness (%)\n2828VISION: Absolute VE of original monovalent and bivalent booster doses \nagainst ED/UC encounters among immuno competent children and \nadolescents, by age group –September 2022 –August 2023\nVE estimates adjusted for age, sex, race and ethnicity, geographic region, and calendar time. Updated from: Link -Gelles et al., MMWR, https://www.cdc.gov/mmwr/volumes/72/wr/mm7221a3.htm\n* These estimates are imprecise, which might be due to there being a relatively small number of persons in each level of vacc ination or case status. This imprecision indicates that the actual VE \ncould be substantially different from the point estimate shown, and estimates should therefore be interpreted with caution. A dditional data accrual could increase precision and allow more precise \ninterpretation.mRNA Dosage PatternTotal\ntestsSARS -CoV -2-\ntest -positive,\nN (%)Median interval\nsince last dose,\ndays (IQR)Adjusted VE\n(95% CI)\n5-17 years\nUnvaccinated (ref) 41,910 1,446 (4) -- Ref\nOriginal monovalent doses only 28,369 1,092 (4) 334 (253 -439) 7 (-1 to 15)\nBivalent booster, 7 -59 days earlier 1,858 30 (2) 30 (18 -44) 63 (46 to 74)\nBivalent booster, 60 -119 days earlier 1,268 37 (3) 89 (74 -105) 36 (10 to 54)\n5-11 years\nUnvaccinated (ref) 31,608 905 (3) -- Ref\nOriginal monovalent doses only 14,956 396 (3) 309 (193 -368) 13 (2 to 24)\nBivalent booster, 7 -59 days earlier 1,004 13 (1) 29 (17 -42) 62 (34 to 78)\n12-17 years\nUnvaccinated (ref) 10302 541 (5) -- Ref\nOriginal monovalent doses only 13413 696 (5) 394 (291 -496) 2 (-11 to 13)\nBivalent booster, 7 -59 days earlier 854 17 (2) 32 (19 -47) 64 (40 to 78)\n-40 -20 0 20 40 60 80 100\nVaccine Effectiveness (%)\n29\nUpdated estimates of VE against \nsymptomatic infection among children and \nadolescents aged 5 –17 and adults aged ≥18 \nyears29\n30▪Absolute VE: comparing the frequency of health outcomes in vaccinated and \nunvaccinated people \n–E.g., comparing outcomes in people vaccinated with an updated bivalent booster versus no \nvaccine at all\n▪Relative VE: comparing the frequency of health outcomes in people who received \none type of vaccine to people who received a different vaccine or by comparing \npeople who received more vaccine doses to those who received fewer doses \n–E.g., comparing outcomes in people vaccinated with an updated bivalent booster versus \nmonovalent vaccine only\n▪In the analyses presented today, relative vaccine effectiveness can be interpreted as \nthe additional protection provided by an updated bivalent booster among people \nwho already received monovalent COVID -19 vaccinesInterpreting absolute and relative vaccine effectiveness \n31▪Nationwide community -based drive -through SARS -CoV-2 testing via pharmacies\n▪Self-reported vaccine history at time of registration for COVID -19 testing\n▪Design : Test -negative, case -control analysis*\n▪Population : Children and adolescents aged 5 –17 years and adults aged ≥18 years with ≥1 COVID -like \nsymptom and nucleic acid amplification testing (NAAT)\n▪Exclusion criteria: Excluded individuals <4 months from last monovalent dose and individuals with \nimmunocompromising conditions\n▪Periods for analysis:\n•Tested: December 1, 2022 –February 13, 2023**\n•Includes periods of both BA.5 -related sublineage and XBB/XBB.1.5 sublineage predominanceICATT: Relative VE of bivalent booster against symptomatic infection in \nchildren and adolescents aged 5 –17 years and adults aged ≥18 years\n*Models adjusted for: age, gender, race, ethnicity, social vulnerability index and HHS region of the testing location, underlyin g conditions (presence versus absence), local incidence (cases per 100,000 by individual county and \nstate in the 7 days before test date), and date of testing\n**Analysis is an update of data published in Link -Gelles R, Ciesla AA, Roper LE, et al. Early estimates of bivalent mRNA booster dose vaccine effectiveness in preventing symptomatic SARS -CoV-2 infection attributable to SARS -CoV-\n2 Omicron BA.5 -related and XBB/XBB.1.5 -related sublineages among immunocompetent adults —Increasing Community Access to Testing Program, United States, December 2022 –January 2023. MMWR Morb Mortal Wkly Rep \n2023;72.  https://www.cdc.gov/mmwr/volumes/72/wr/mm7205e2.htm31\n3232ICATT: Relative VE of bivalent booster against symptomatic infection in children and \nadolescents aged 5 –17 years, December 1, 2022 –February 13, 2023*\n*Unpublished CDC data. Age group, years/mRNA Dosage PatternTotaltestsSARS -CoV -2 positive tests, Adjusted VE\nN (row %) (95% CI)\n5-11 years (authorized for bivalent booster \non October 12, 2022 )\nReceived 2 -3monovalent doses only (Ref) 4,855 1,433 (30) Ref\n2 weeks -1 month since bivalent booster 600 73 (12) 65 (55 to 73)\n2-3 months since bivalent booster 881 139 (16) 54 (43 to 62)\n4-5 months since bivalent booster 58 10 (17) ----\n12-17 years (authorized for bivalent booster \non September 1, 2022)\nReceived 2 -3 monovalent doses only (Ref) 8,243 3,194 (39) Ref\n2 weeks -1 month since bivalent booster 443 73 (16) 68 (58 to 75)\n2-3 months since bivalent booster 1,122 230 (20) 56 (49 to 62)\n4-5 months since bivalent booster 283 68 (24) 53 (37 to 64)\n0 20 40 60 80 100\nVaccine Effectiveness %\n33ICATT: Relative VE of bivalent booster against symptomatic infection in adults aged \n≥18 years, December 1, 2022 –February 13, 2023*\n*Unpublished CDC data. 33Age group, years/mRNA Dosage PatternTotaltestsSARS -CoV -2 positive tests, Adjusted VE\nN (row %) (95% CI)\n18-49 years\nReceived 2 -3 monovalent doses only (Ref) 182,741 82,043 (45) Ref\n2 weeks -1 month since bivalent booster 10,758 3,127 (29) 51 (49 to 53)\n2-3 months since bivalent booster 32,577 10,206 (31) 45 (43 to 46)\n4-5 months since bivalent booster 9,197 2,882 (31) 41 (38 to 44)\n50-64 years\nReceived 2 -4 monovalent doses only (Ref) 60,822 31,878 (52) Ref\n2 weeks -1 month since bivalent booster 6,223 2,331 (37) 46 (43 to 49)\n2-3 months since bivalent booster 18,399 7,898 (43) 32 (29 to 34)\n4-5 months since bivalent booster 4,837 2,030 (42) 28 (23 to 32)\n≥65 years\nReceived 2 -4 monovalent doses only (Ref) 28,307 14,246 (50) Ref\n2 weeks -1 month since bivalent booster 4,579 1,788 (39) 38 (34 to 42)\n2-3 months since bivalent booster 19,071 8,080 (42) 27 (25 to 30)\n4-5 months since bivalent booster 5,796 2,431 (42) 21 (16 to 26)\n0 20 40 60 80 100\nVaccine Effectiveness %", "summary": "1 Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. Updates to COVID -19 vaccine effectiveness (VE) in  the U.S September 12, 2023 Ruth Link -Gelles, PhD, MPH CDR, US Public Health Service COVID -19 Vaccine Effectiveness…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-september-12-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-09-12/05-COVID-Link-Gelles-508.pdf", "doc_date": "2023-09-12", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 33}
{"title": "06 COVID Prosser 508", "content": "Economic Analysis of Vaccination\nwith mRNA Booster Dose \nagainst COVID -19 Among Adults\nUniversity of Michigan \nCOVID -19 Vaccination Modeling Team\nPresentation to ACIP\nSeptember 12, 2023\n1\nStudy Team\nUniversity of Michigan\n•Lisa A. Prosser, PhD, Principal Investigator\n•David W. Hutton, PhD, Co -Investigator\n•Acham Gebremariam, MS, Programmer/Analyst\n•Angela Rose, MS, MPH, Project Manager\n•Kerra Mercon, MS, Research Assistant\nWake Forest University\n•Cara Janusz, PhD\nAdditional contributors to 2021 Covid Vaccination Model:\nMarisa Eisenberg, Emily Martin, Grace Chung, Janamarie \nPerroud, Ellen Kim Deluca, Chris Cadham, Huey -Fen Chen, \nAnton L.V. Avancena, Tran Doan, David SuhCenters for Disease Control and Prevention\n•Jamie Pike, PhD, Health Economist, Project officer\n•Megan Wallace, DrPH, Epidemiologist\n•Ismael Ortega -Sanchez, PhD, Senior Economist\n•Andrew Leidner, PhD, Economist\n•Fangjun Zhou, PhD, Health Scientist\n•Melisa Shah, MD, MPH, Medical Epidemiologist \n•Danielle Moulia, MPH, Health Scientist \n•Ruth Link -Gelles, PhD, Epidemiologist\n•Sharon Saydah, PhD, Epidemiologist\n2\nConflict of interest statement\n3Authors have no known conflicts of interest. \nObjectives\n•Estimate annual disease burden and healthcare utilization associated with \nCOVID -19 illness and COVID -19 booster vaccination, including cases of \nsymptomatic illness, hospitalizations, deaths, adverse events, costs, and quality -\nadjusted life years\n•Project cost -effectiveness of an updated mRNA booster against COVID -19-\nassociated illness in persons ages ≥18 years\n4\nMethods\n•Intervention strategies:\noVaccination against COVID -19 illness with an updated “generic” mRNA booster\noNo updated mRNA booster (vaccination against COVID -19 illness with primary series only or \nprimary series plus current booster)\n•Target population: all US adults, stratified by age\no18-49 y, 50 -64 y, 65+ y\noPediatric and adolescent age groups excluded from current analysis, insufficient data to \nincorporate into this first phase analysis\n•Time horizon: 1 year*\n•Perspective: Societal\n•Costing year: 2023$\n•Discount rate: 3%\n* Costs and QALYs lost due to long -term sequelae and deaths beyond one year are included\n5\nVaccinationSymptomatic \nCOVID -19\n(non -hospitalized) \nHospitalized\nCOVID -19Non -medically \nattended*\nOutpatient visit\nNo ICU \nadmission\nICU admissionNo side \neffects\nSystemic \nreaction\nAnaphylaxis\nSevere \nadverse eventA\nA\nA\nANo booster\nAB\nNo \ncomplications\nLong Covid \nNo ventilator\nVentilatorB\nCDeathModel schematic\nNo\nCOVID -19\nCOVID -19No long Covid\nLong Covid\nLong -term \nsequelae C\nNo \ncomplications\nLong Covid \nDeath\n6ED visit B\n*Includes probability and costs of testing\nED= emergency department; ICU= intensive care unit\nAnalysis Plan\n•Project health and economic outcomes stratified by intervention strategy and by \nage subgroups (18 -49y, 50 -64y, 65+y)\noCases\noHospitalizations\noDeaths\noCosts\noQALYs\noAdverse events\n•Calculate incremental cost -effectiveness ratios comparing updated mRNA booster \nto no booster\n•Conduct base case and uncertainty analyses (one -way sensitivity and scenario \nanalyses)\n***This presentation reports preliminary results from the first phase of an ongoing \nanalysis***\n7\nNatural history: \nprobability of symptomatic infection, outpatient/ED \nvisits, hospitalization, and critical illness\n8\nAnnual probability of symptomatic infection\n9Overall\n02000040000\n12345678910111212345678910111212345\n2021 2022 2023Rate/100,000/month\n18-49y 50-64y 65+yLast 6 months\nSource: HEROES -RECOVER, unpublished dataAnnualized probability \nbased on last 6 months\n12/22 -5/23\n18-49 y 0.3145\n50-64 y 0.2841\n65+ y 0.3339\nAnnual probability of symptomatic infection\n10Annualized probability based on last 6 months\n12/22 -5/23\nAge group Base caseRange for sensitivity analysis\nLow High\n18-49 y 0.3145 0.2858 0.3444\n50-64 y 0.2841 0.2438 0.3274\n65+ y 0.3339 0.2312 0.4510\nSource: HEROES -RECOVER, unpublished data\n05001,0001,5002,0002,5003,000\n10\n202011 12 1\n20212 3 4 5 6 7 8 9 10 11 12 1 2\n20223 4 5 6 7 8 9 10Visits/100,000 Enrollees/month\n18 - 49 Years 50 - 64 Years 65+ YearsProbability of an outpatient visit\n11Annualized Probability based on last 6 months\n5/22 -10/22\nAge \ngroupBaseRange for sensitivity \nanalysis\nLow High\n18-49 y 0.075 0.022 0.110\n50-64 y 0.106 0.041 0.159\n65+ y 0.111 0.040 0.150Last 6 months\nSource: Merative™MarketScan® Research Database, unpublished data \nProbability of outpatient visits and ED visits given\nsymptomatic illness\n12Age group BaseRange for sensitivity analysis\nLow High\nOutpatient visits given symptomatic illness\n18 -49 y 0.157 0.1483 0.1664\n50 -64 y 0.215 0.1991 0.2335\n65+ y 0.244 0.1996 0.3088\nEmergency department visits given symptomatic illness\n18 -49 y 0.0184 0.0172 0.0196\n50 -64 y 0.0191 0.0175 0.0210\n65+ y 0.0394 0.0318 0.0505\nSource: Derived using probability of an outpatient visit or ED visit from MarketScan data ( Merative™MarketScan® Research \nDatabase, unpublished data) and probability of symptomatic illness in the HEROES -RECOVER data, May 2022 -October 2022 \n(unpublished)\n050100150200250300350400\n91011121234567891011121234567891011121234\n2020 2021 2022 2023Rate/100,000/month\n18-49 years 50-64 years 65+ yearsAnnual probability of hospitalization\n13Annualized Probability based on last 6 months\n10/22 -3/23\nAge group Base caseRange\nLow High\n18-49 y 0.00144 0.00080 0.00204\n50-64 y 0.00335 0.00216 0.00479\n65+ y 0.01453 0.00967 0.02090Last 6 months\nSource: COVID -NET, unpublished dataRate/100,000 based on last 6 months\n10/22 -3/23\nAge groupBase case\nper 100,000Range\nLow High\n18-49 y 144 80 204\n50-64 y 335 216 479\n65+ y 1453 967 2090\nProbability of critical illness given hospitalization\n14Probability Base caseRange for sensitivity analysis (95% CI)\nLow High\nProbability ICU given hospitalization \n18-49 y 0.123 0.119 0.145\n50-64 y 0.200 0.178 0.208\n65+ y 0.144 0.138 0.163\nProbability ventilator use given ICU\n18-49 y 0.525 0.472 0.577\n50-64 y 0.488 0.445 0.532\n65+ y 0.386 0.342 0.432\nSource: COVID -NET, unpublished data\nICU= intensive care unit\nProbability of death given hospitalization\n15Source: COVID -NET, unpublished data\nICU= intensive care unitProbability Base caseRange (95% CI)\nLow High\nProbability of death given no ICU\n18-49 y 0.006 0.002 0.008\n50-64 y 0.009 0.007 0.016\n65+ y 0.030 0.022 0.035\nProbability of death given ICU without ventilator\n18-49 y 0.024 0.003 0.040\n50-64 y 0.047 0.026 0.077\n65+ y 0.166 0.144 0.233\nProbability of death given ICU with ventilator\n18-49 y 0.284 0.213 0.368\n50-64 y 0.379 0.301 0.435\n65+ y 0.628 0.476 0.637\nProbability of long COVID\n16Age group Base caseRange\nLow High\n18-49 y 0.072 0.058 0.091\n50-64 y 0.072 0.058 0.091\n65+ y 0.072 0.058 0.091\nSource: Montoy JCC et al. Prevalence of Symptoms ≤12 Months After Acute Illness, by COVID -19 Testing Status Among Adults —Unite d States, December 2020 –\nMarch 2023. MMWR 2023; 72 (32): 859 -865.Assumptions :\n•Derived to reflect 5 -month median duration of episode of long covid for individuals who experience \nsymptoms for 3+ months\n•Average prevalence of HEENT, constitutional, pulmonary, musculoskeletal, cognitive, and fatigue symptoms \nat 5 months\n•Current estimates do not reflect higher risk associated with age or with severity of illness\nVaccine effectiveness & adverse events\n17\nVaccine effectiveness: hospitalization, 18+ y\n1862%\n47%\n24%57%\n41%\n12%67%\n53%\n33%\n0%20%40%60%80%100%\n0 73 146 219 292 365Vaccine Efficacy Against Hospitalization (%) Interval Days since Last Dose (days)VISION(Sep 2022 -May 2023)\n62%\n47%\n24%\n0%20%40%60%80%100%\n0 73 146 219 292 365Vaccine Efficacy Against Hospitalization (%)\nInterval Days since Last Dose (days)VISION (Sep 2022 -May 2023)\nSource: VISION, bivalent booster, Sept 2022 -May 2023 . Link -Gelles R. Monovalent and bivalent VE against hospitalization among adults aged \n≥18 years. Paper presented at: Advisory Committee on Immunization Practices. June 2023Conservative scenarioOptimistic scenario\nVaccine effectiveness: hospitalization, 18+ y\n1954%\n34%\n6%39%\n15%65%\n50%\n30%\n0%20%40%60%80%100%\n0 73 146 219 292 365Vaccine Efficacy against Hospitalization (%)\nInterval Time since Last Dose (days)IVY (Sep 2022 -May 2023)\n54%\n34%\n6%\n0%20%40%60%80%100%\n0 73 146 219 292 365Vaccine Efficacy against Hospitalization (%) \nInterval Time since Last Dose (days)IVY (Sep 2022 -May 2023)\nSource: IVY , bivalent booster, Sept 2022 -May 2023. Link-Gelles R. Monovalent and bivalent VE against hospitalization among adults aged \n≥18 years. Paper presented at: Advisory Committee on Immunization Practices. June 2023Conservative scenarioOptimistic scenario\nVaccine effectiveness: hospitalization, 18+ y\n20Source: VISION and IVY, bivalent vaccination, \nSept 2022 -May 2023 . Link -Gelles R. Monovalent \nand bivalent VE against hospitalization among \nadults aged ≥18 years. Paper presented at: \nAdvisory Committee on Immunization Practices. \nJune 2023Area under the curve: 0.2690%20%40%60%80%100%\n0 73 146 219 292 365Vaccine Efficacy Against Hospitalization (%)\nInterval Days since Last Dose (days)Lower boundUpper boundVISION (Sep 2022 -May 2023)\n0%20%40%60%80%100%\n0 73 146 219 292 365Vaccine Efficacy Against Hospitalization (%)\nInterval Days since Last Dose (days)Lower boundUpper boundIVY (Sep 2022 -May 2023)\n61%\n46%\n22%\n0%20%40%60%80%100%\n0 73 146 219 292 365Vaccine Efficacy Against Hospitalization (%)\nInterval Days since Last Dose (days)Combined -VISION and IVY (Sep 2022 -May 2023)\nVaccine effectiveness, hospitalization, 18+ y\n21Linear waning Conservative Optimistic\nVISION\nBase case 0.278 0.217 0.339\nLower bound 0.210 0.180 0.240\nUpper bound 0.334 0.250 0.418\nIVY\nBase case 0.168 0.153 0.183\nLower bound 0.088 0.088 0.088\nUpper bound 0.313 0.237 0.389\nBase Case* 0.269 0.088 0.418\n* Base case includes a weighted average of the area under the vaccine effectiveness (VE) curve with the assumption that VE wane s linearly after 180 days. Range s were\nselected by taking the minimum and maximum of the individual dataset VEs, applying a conservative approach (assuming VE drops to0 at 180 days) for the lower bound \nand an optimistic approach for the upper bound (assuming VE at 365 days=VE at 180 days)\nSummary, vaccine effectiveness\n22Base case Low High\nSymptomatic illness (non -hospitalized)*\nHospitalization, uncomplicated 0.269 0.088 0.418\nHospitalization, critical illness** 0.403 0.191 0.671\nDeath 0.403 0.191 0.671\nSource: VISION and IVY , Link-Gelles R. Monovalent and bivalent VE against hospitalization among adults aged ≥18 years. Paper \npresented at: Advisory Committee on Immunization Practices. June 2023* Non -medically attended illness, illness that includes an outpatient or ED visit\n** Intensive care unit with or without mechanical ventilation \nSummary, vaccine effectiveness\n23Base case Low High\nSymptomatic illness (non -hospitalized)* 0.269 0.088 0.418\nHospitalization, uncomplicated 0.269 0.088 0.418\nHospitalization, critical illness** 0.403 0.191 0.671\nDeath 0.403 0.191 0.671\nSource: VISION and IVY , Link-Gelles R. Monovalent and bivalent VE against hospitalization among adults aged ≥18 years. Paper \npresented at: Advisory Committee on Immunization Practices. June 2023* Non -medically attended illness, illness that includes an outpatient or ED visit\n** Intensive care unit with or without mechanical ventilation \nProbability of adverse events \n24Base caseRange for sensitivity analysis\nSource\nLow High\nSystemic reaction\n18-49 y 0.106 0.073 0.148\n1,2 50-64 y 0.106 0.073 0.148\n≥65 y 0.137 0.107 0.171\nAnaphylaxis (all ages) 0.00000495 0.0000032 0.0000074 3\nDeath given anaphylaxis 0 0 0.00966 Assumption, 4\nMyocarditis\n18 -29 y 0.0000238 0.0000085 0.0000838 5\n30-39 y 0.0000087 0.0000008 0.0000375 5\n40+  y 0 0 0 Assumption\nDeath given myocarditis 0.0005 0 0.001 Expert opinion\n1. U.S. Food and Drug Administration. Fact Sheet for Healthcare Providers Administering Vaccine: Emergency Use Authorization of Moderna COVID -19 Vaccine, Bivalent (Original \nand Omicron BA.4/BA.5). In: U.S. Department of Health and Human Services, ed2023.\n2. U.S. Food and Drug Administration. Fact Sheet for Healthcare Providers Administering Vaccine: Emergency Use Authorization o f Pfizer -Biontech COVID -19 Vaccine, Bivalent \n(Original and Omicron BA.4/BA.5). In: U.S. Department of Health and Human Services, ed2023.\n3. Klein NP, Lewis N, Goddard K, et al. Surveillance for Adverse Events After COVID -19 mRNA Vaccination. JAMA. 2021;326(14):1390 -1399.\n4.Su JR, Moro PL, Ng CS, Lewis PW, Said MA, Cano MV. Anaphylaxis after vaccination reported to the Vaccine Adverse Event Repor ting System, 1990 -2016. J Allergy Clin Immunol. \n2019;143(4):1465 -1473.\n5. Kristin Goddard KEH, Ned Lewis,. Incidence of Myocarditis/Pericarditis Following mRNA COVID -19 Vaccination Among Children and Yo unger Adults in the United States. Annals of \nInternal Medicine. 2022;175(12):1169 -1771.\nCosts: Direct medical costs and productivity losses \n25\nDirect medical costs\nVariable Base caseRange for sensitivity analysis\nSource \nLow High\nTesting\nTest cost $8 $8 $62 1,2\nProbability of testing 0.05 0.02 0.20 3\nRecipient time (hours) 0.50 0.25 1.50 Assumption\nOutpatient visit\n18-49 y $372 $370 $375\n4 50-64 y $380 $377 $384\n65+ y $391 $386 $396\nLong Covid $1091 $1018 $1165 5\n261. Justin Lo CC, Krutika Amin, Imani Telesford, Lindsey Dawson, and Jennifer Kates. Prices for COVID -19 testing. 2023; https://www.healthsystemtracker.org/brief/prices -for-covid -19-\ntesting/#Prices%20for%20COVID -19%20tests%20in%20the%20outpatient%20setting,%20among%20people%20with%20large%20employer%20health% 20coverage,%202021 .\n2. Walmart. COVID -19 Test Kits.  https://www.walmart.com/browse/home -diagnostic -tests/covid -19-test-kits/976760_1005860_542089_3092061 . Accessed September 1, 2023.\n3. Rader B GA, Iuliano AD,. Use of At -Home COVID -19 Tests —United States, August 23, 2021 –March 12, 2022\n4. Merative™MarketScan® Research Database, unpublished data \n5. Pike J et al. Direct Medical Costs Associated With Post –COVID -19 Conditions Among Privately Insured Children and Adults. Prev Ch ronic Dis. 2023;20 (6) \nDirect medical costs, cont.\nVariable Base caseRange for Sensitivity Analysis\nLow High\nHospitalization episode\n18-49 y$32,514 $28,505 $36,523\n50-64 y$32,854 $31,450 $34,258\n65+ y$20,648 $20,295 $21,000\nICU episode (no ventilator)\n18-49 y $37,159 $30,116 $44,203\n50-64 y $46,727 $40,269 $53,186\n65+ y $23,220 $22,408 $24,032\nICU (with ventilator) episode\n18-49 y $245,432 $168,362 $322,503\n50-64 y $169,189 $140,250 $198,129\n65+ y $55,257 $50,705 $59,809\n27ICU= Intensive care unitSource: Merative ™MarketScan® Research Database, unpublished data \nMedication costs\nVariable Base caseRange for Sensitivity Analysis\nSource \nLow High\nOver the counter medication* $4.12 - - 1\nProbability of nirmatrelvir -r prescription \ngiven an outpatient visit\n18-49 years 0.1751 0.10 0.30\n2,3, Assumption 50-64 years 0.2696 0.10 0.50\n65+ years 0.2739 0.10 0.50\nCost, nirmatrelvir -r $530 $530 $1200 4, 5\n28*5 days of generic cold/flu medicine\n1. Target.com Accessed August 29, 2023.\n2. HealthVerity, Inc. COVID -19 database licensed by CDC, unpublished data\n3. Merative™MarketScan® Research Database, unpublished data\n4. Recht H. Paxlovid Has Been Free So Far. Next Year, Sticker Shock Awaits. 2022; https://kffhealthnews.org/news/article/paxlovid -covid -sticker -shock -\ninsurance/#:~:text=The%20U.S.%20government%20has%20so,in%20a%20July%20earnings%20call .\n5. Murez C. Paxloid soon won’t be free for Americans. 2022  https://www.usnews.com/news/health -news/articles/2022 -12-07/paxlovid -soon -wont -be-free-for-americans . Accessed September 7, 2023\nVaccine receipt, costs\nVariable Base caseRange for Sensitivity Analysis\nSource \nLow High\nmRNA monovalent booster, per dose* $120 $30 $200 1, expert opinion\nAdministration, per dose** $20.33 $18.07 $26.58 2\nVaccination setting\nProportion, pharmacy 0.644 0.625 0.663 3\nProportion, physician office visit 0.256 0.221 0.294 3\nProportion, mass vaccination 0.100 0.075 0.155 3\nRecipient time by vaccination setting (hours)\nPharmacy 0.25 0.083 0.50 4, expert opinion\nPhysician office 1.19 0.17 2 4\nMass vaccination 0.195 0 0.390 4\nMean hourly earnings $33.74 $23.98 $50.16 5\n29*Lower bound reflects current price of COVID -19 boosters\n**CPT 90471\n1. Kates J et al. How much could COVID -19 vaccines cost the US after commercialization? 2023. https://www.kff.org/coronavirus -covid-19/issue -brief/how -much -could -covid -19-vaccines -cost-the-u-s-after -\ncommercialization/\n2. Centers for Medicare & Medicaid Service. Search the Physician Fee Schedule. 2023; https://www.cms.gov/medicare/physician -fee-schedule/search?Y=0&T=0&HT=0&CT=3&H1=90471&M=5\n3. CDC national survey data, 2/10/23 -5/1/23, unpublished\n4. Prosser L, O'Brien M, Molinari N, et al. Non -traditional settings for influenza vaccination of adults: Costs and cost -effectiv eness. Pharmacoeconomics. 2008;26(2):163 -178.\n5.US Bureau of Labor Statistics. Average hourly and weekly earnings of all employees on private nonfarm payrolls by industry se ctor, seasonally adjusted. 2023; https://www.bls.gov/news.release/empsit.t19.htm\nVaccination -associated adverse events, costs\nVariable Base caseRange for Sensitivity AnalysisSource \nLow High\nSystemic reaction\nPhysician visit $90.82 $82.72 $115.84 1\nProductivity loss (days) 1 - - Assumption\nAnaphylaxis\nHospitalization $5035 2*\nProductivity loss (days) 1 1 3 3\nMyocarditis/pericarditis\nHospitalization $75,927 4**\nProductivity loss (days) 4 0 14 5, 6, Expert opinion\n30* HCUP -NIS 2012 estimates (mean LOS = 4.9 days) adjusted to 1 days LOS\n** HCUP -NIS 2014 estimates (mean LOS = 7.4 days) adjusted to 4 days LOS\n1. Centers for Medicare & Medicaid Service. Search the Physician Fee Schedule. 2023; https://www.cms.gov/medicare/physician -fee-schedule/search?Y=0&T=0&HT=0&CT=3&H1=90471&M=5\n2. Candrilli S, Kurosky SK. Recent Trends In Anaphylaxis -Related Hospitalization In The United States. Value in Health. 2015;18(7):A503.\n3. Shimabukuro T, Cole M, Su JR. Reports of Anaphylaxis After Receipt of mRNA COVID -19 Vaccines in the US -December 14, 2020 -Januar y 18, 2021. Jama. 2021;325(11):1101 -1102.\n4. Khorolsky C, Shi J, Chkhikvadze T. Trends In Hospitalization Costs, Length Of Stay And Complications Among Patients With Acut e Myocarditis: A 10 -Year United States Perspective. Journal of the American College \nof Cardiology. 2019;73(9_Supplement_1):935 -935.\n5. Marshall M, Ferguson I, Lewis P, et al. Symptomatic Acute Myocarditis in Seven Adolescents Following Pfizer -BioNTech COVID -19 Va ccination. Pediatrics. 2021.\n6. Shimabukuro T. COVID -19 Vaccine Safety Updates. In. Advisory Committee on Immunization Practices (ACIP)2021.\nQuality adjustments\n31\nQALY losses, COVID -19 illness\n32Variable Base CaseRange for Sensitivity Analysis\nQALDs lostLow High\nSymptomatic illness* 0.006 0.004 0.008 2.2 (1.5 -2.9)\nHospitalization 0.027 - - 9.9 \nCritical illness** 0.054 - - 19.7\nLong COVID 0.067 0.038 0.088 24.3 (13.7 -31.9)\n* Non -medically attended and outpatient illness\n** Intensive care unit with mechanical ventilation. Derived by applying the ratio of ICU to hospitalization QALY loss (2x) to the \nhospitalization QALY loss from SARS CoV -2 EQ5D Study. The model also includes a health state for ICU care without ventilator use for \nwhich QALY loss is interpolated using QALY loss for hospitalization and critical illnessDRAFT\nSource: Coronavirus Household Evaluation and Respiratory Testing (C -HEaRT) and Prospective Assessment of COIVD -19 in a Community (PACC), unpublished data\nQALY loss, vaccination -associated AEs\n33Variable Base CaseRange for Sensitivity Analysis\nQALDs lost Source\nLow High\nSystemic reaction (QALY loss)*\nAll ages 0.0004 0.0003 0.0005 0.15 (0.11 -0.18) Assumption \nAnaphylaxis (QALY loss)\nAll ages 0.0137 0.0135 0.0139 5.0 (0.93 -5.08) 1\nMyocarditis/pericarditis (QALY loss)\nAcute illness** 0.010 0.0086 0.0112 3.65 (3.14 -4.09) 2\n* QALY loss equal to one day of COVID -19 illness\n** Derived from health utility for COVID -19 related myocarditis. Assumed 2 -week illness\nQALY= Quality -adjusted life year; QALD= Quality -adjusted life day\n1. Prosser LA, Payne K, Rusinak D, Shi P, Uyeki TM, Messonnier ML. Valuing health across the lifespan: health state preferences forseasonal influenza illnesses in patients of different ages. Value in \nHealth. 2011;14(1):135 -143.\n2. Morrow AJ, Sykes R, McIntosh A, et al. A multisystem, cardio -renal investigation of post -COVID -19 illness. Nature Medicine. 2022;28(6):1303 -1313\nResults\npreliminary estimates\n34\nDisaggregated results, per 100,000\npreliminary estimates\nAge \ngroupStrategyCases Cases Averted\nCases Hosp ICU Deaths Cases Hosp ICU Deaths\n18-49 y No booster 31,450 144 17.7 3.6 - - - -\nBooster dose 22,990 105 10.6 2.2 8,460 39 7.1 1.4 \n50-64y No booster 28,410 335 67.1 16.4 - - - -\nBooster dose 20,768 245 40.0 9.9 7,642 90 27.0 6.6 \n65+ yNo booster 33,390 1,453 209.3 109.4 - - - -\nBooster dose 24,408 1,062 124.9 66.0 8,982 391 84.3 43.4 \n35\nIncremental cost -effectiveness ratios, \nsocietal perspective, per 1000\npreliminary estimates\nAge group StrategyProjected\nCostsIncremental\nCostsProjected\nQALYsIncremental \nQALYs$/QALY\n18-49 y No booster $192,335 - 20207.0670 - -\nBooster vaccination $293,503 $101,168 20207.9423 0.8752 $115,588\n50-64y No booster $385,752 - 12275.8345 - -\nBooster vaccination $421,249 $35,498 12277.2111 1.3766 $25,787\n65+ y No booster $642,488 - 6519.9466 - -\nBooster vaccination $598,857 -$43,630 6523.5511 3.6046 Cost -saving\n36QALY= quality -adjusted life year\nIncremental cost -effectiveness ratios, \nsocietal perspective, per 1000\npreliminary estimates, w/pooled 18+ \nAge groupBooster Dose,\n$/QALY\n18-49 y$115,588\n50-64 y$25,787\n65+ yCost -saving\n18+ y$33,437\n37QALY= quality -adjusted life year\nOne way sensitivity analyses, 18 -49 y\npreliminary estimates\n38Base case: $115,588 *Non -hospitalized cases\nNote: Numbers next to bars indicate input values for sensitivity analysis\nVE=vaccine effectiveness; QALY=Quality -adjusted life year$0 $50,000 $100,000 $150,000 $200,000 $250,000 $300,000Probability, symptomatic COVID-19Time (h), vaccination, doctor's officeLifetime productivity costVE, hospitalizationProbability, death given ICU with ventilatorQALYs lost symptomatic COVIDProbability, hospitalizationVE, critical illnessVE, symptomatic COVID-19Cost, vaccine\n$/QALY$30 $200\n0.418 0.088\n0.671 0.191\n0.002 0.0008\n0.008 0.004\n0.368 0.213\n0.418 0.088\n$2,382,347\n0.17 2\n0.344 0.286*\nVE scenario analyses \npreliminary estimates\nBase case Scenario 1 Scenario 2 Scenario 4 Scenario 5\nVE inputs\nSymptomatic illness 0.269 0.088 0.418 0.269 0.403\nHospitalization, uncomplicated 0.269 0.088 0.418 0.269 0.403\nHospitalization, critical illness 0.403 0.191 0.671 0.269 0.403\nDeath 0.403 0.191 0.671 0.269 0.403\n$/QALY\n18-49 y $115,588 $435,886 $45,376 $141,155 $70,928\n50-64 y $25,787 $199,830 Cost -saving $51,792 $3,001\n65+ y Cost -saving $51,782 Cost -saving Cost -saving Cost -saving\n39VE= vaccine effectiveness; QALY= quality -adjusted life year\nScenario analyses: \nprobability of symptomatic illness, non -hospitalized*\npreliminary estimates\n40Age group Base case 0.1 0.2 0.3 0.4 0.5\n18-49 y $115,588 $229,724 $160,000 $120,013 $94,082 $75,905\n50-64 y $25,787 $48,937 $34,724 $24,324 $16,384 $10,123\n65+ y Cost -saving Cost -saving Cost -saving Cost -saving Cost -saving Cost -saving\nQALY=Quality -adjusted life year\n*One -way sensitivity analysis of non -hospitalized symptomatic illness varied separately from hospitalization and critical illnes s; \nbase case probability of symptomatic illness: 18 -49 y, 0.3145; 50-64 y, 0.2841; 65+ y, 0.3339\nScenario analysis: \nprobability of hospitalization\npreliminary estimates\n41Age group Base case* 2x base case 3x base case 4x base case\n18-49 y $115,588 $51,978 $14,541 Cost -saving\n50-64 y $25,787 Cost -saving Cost -saving Cost -saving\n65+ y Cost -saving Cost -saving Cost -saving Cost -saving\nQALY=Quality -adjusted life year\n*Base case probability of h ospitalization 18-49 y-0.00144; 50 -64 y-0.00335; 65+ -0.01453\nScenario analysis: probability of critical care\npreliminary estimates\n42Age groupProbability of ICU given hospitalization\nBase case* 2x 3x 4x\n18-49 y $115,588 $71,487 $42,307 $21,570\n50-64 y $25,787 Cost -saving Cost -saving Cost -saving\n65+ y Cost -saving Cost -saving Cost -saving Cost -saving\nQALY=Quality -adjusted life year; ICU= Intensive care unit\n*Base case probability of ICU given hospitalization: 18 -49 y-0.123; 50 -64 y-0.200, 65+ y -0.144\nScenario analysis: vaccine setting\npreliminary estimates\n43Age group Base case*100%  \npharmacy100% \nphysician office100% \nmass vaccination\n18-49 y $115,588 $106,523 $142,759 $104,403\n50-64 y $25,787 $20,024 $43,063 $18,676\n65+ y Cost -saving Cost -saving Cost -saving Cost -saving\nQALY=Quality -adjusted life year\n*Base case : Physician office visit -0.256, Pharmacy -0.644, Mass vaccination -0.100 \nLimitations\n▪Unpublished data used to derive key parameters in the model: vaccine effectiveness, \nsymptomatic illness, probabilities of hospitalization and critical illness\n▪Data sources vary in representativeness, generalizability\n▪VE estimates derived from data on bivalent booster \n▪Hospitalization rates may overestimate cases due to COVID -19 for younger age groups\n▪MarketScan data for ages 65+ only includes those with supplemental insurance\n▪Evidence base for long covid is especially scarce –future analyses will incorporate adjustments \nto reflect differences in probability and duration of long covid by age and severity of illness\n▪Cost estimates for long covid may not reflect current practice patterns or rates of HC utilization\n44\nSummary -preliminary estimates\n•Vaccination averts substantial morbidity and mortality as \ndemonstrated through estimated disaggregated outcomes\n•ICERs for 50 -64y and 65+ age groups are robust to changes in \nparameter inputs across plausible ranges in all but one scenario \n(<$51,800 or cost -saving)\n•ICERs for 18 -49y are sensitive to changes in parameter inputs; more \nfavorable for higher VE, higher risk of hospitalization and critical \nillness\n45", "summary": "Economic Analysis of Vaccination with mRNA Booster Dose  against COVID -19 Among Adults University of Michigan  COVID -19 Vaccination Modeling Team Presentation to ACIP September 12, 2023 1 Study Team University of Michigan •Lisa A. Prosser, PhD, Principal Investigator •David W. Hutton, PhD, Co -Investigator •Acham Gebremariam, MS, Programmer/Analyst •Angela Rose, MS, MPH, Project Manager •Kerra Mercon, MS, Research Assistant Wake Forest University •Cara Janusz, PhD Additional contributors to…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-september-12-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-09-12/06-COVID-Prosser-508.pdf", "doc_date": "2023-09-12", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 45}
{"title": "07 COVID Klein 508", "content": "COVID -19 Vaccine Safety Surveillance:\nSummary from VSD RCA\nNicola Klein, MD, PhD\nDirector, Kaiser Permanente Vaccine Study Center\nKaiser Permanente Northern California\nAdvisory Committee in Immunization Practices\nSeptember 12, 2023\n\n2Vaccine Safety Datalink\n•Active surveillance: newly licensed vaccines\n̶Rapid Cycle Analysis (RCA) \n•Evaluate vaccine safety:\n̶of new recommendations for existing vaccines\n̶for vaccines in high -risk populations, particularly pregnant women \n(+ other groups)\n•Develop new methods for vaccine safety assessment\n•Test hypotheses that emerge from elsewhere (e.g.,  \nVAERS, clinical trials, other platforms).\n\nStrengths of VSD Rapid Cycle Analysis (RCA)\n▪Population\n•~12.5 million people (equal to ~4% of the U.S. population) across VSD data sites are geographically and \nracially/ethnically diverse\n▪Data \n•Near real -time data, with analyses updated weekly\n•Access to comprehensive medical records, including exposures (vaccination) and outcomes, allowing \nrapid chart reviews to obtain additional clinical information as needed\n▪Innovative Methods\n•Vaccinated concurrent comparators : Recent vaccinees who are beyond their risk interval are expected to \nbe  similar to current vaccinees who are within their risk interval. They serve as better comparators than \nunvaccinated individuals, historical controls or non -concurrent self controls because they permit:\n‒Careful adjustment for potential biases associated with calendar time, site, and demographic \nfactors \n‒Analyses that can begin sooner than alternative methods \n•Supplemental analyses conducted weekly: Unvaccinated/un -boosted comparators would also be available \nto provide context in real time \n3\nAims:\n1. To monitor the safety of COVID -19 vaccines weekly using pre -\nspecified outcomes of interest among VSD members. \n2. To describe the uptake of COVID -19 vaccines over time \namong eligible VSD members overall and in strata by age, site, \nand race/ethnicity.\nSurveillance began in December 2020 and was ready when \nthe first doses of COVID -19 vaccines were given.VSD COVID -19 Vaccine RCA\n4\nInclusion in prior vaccine safety studies\n•Acute disseminated encephalomyelitis \n•Anaphylaxis*\n•Encephalitis / myelitis\n•Guillain -Barré syndrome\n•Immune thrombocytopenia \n•Kawasaki disease \n•Narcolepsy and cataplexy*\n•Seizures \n•Transverse myelitis Hypothetical concerns regarding an \nassociation with COVID -19 disease \n•Acute myocardial infarction  \n•Acute respiratory distress syndrome*\n•Disseminated intravascular coagulation \n•Multisystem Inflammatory Syndrome*  \n•Pulmonary embolism\n•Stroke, hemorrhagic\n•Stroke, ischemic \n•Thrombotic thrombocytopenic purpura \n•Venous thromboembolism  \n5•Cerebral venous sinus thrombosis \n•Myocarditis / pericarditis \n•Thrombosis with thrombocytopenia syndromeOutcomes added/enhanced due to emerging \nconcerns\nImbalances in phase 3 COVID -19 vaccine clinical \ntrials\n•Appendicitis \n•Bell’s palsy\n*monitored without comparators Only chart confirmed cases\nCOVID Vaccine Safety RCA Surveillance: Monitoring \n23 Serious Outcomes   \n\nVaccinee with Myocarditis in Risk Interval and a Concurrent Comparator\nOn each calendar day that an outcome occurred \nin a vaccinee (e.g., June 3), w e compared \nvaccinees in their risk interval (day 1 -21) with \nsimilar vaccinees in their comparison interval (day \n22-42). \nBy similar, we mean they were in the same age \ngroup and of the same sex, race, and at the same \nVSD site. \nComparison Interval 22 -42 days post -vaccination 42 22\n June 3\nVaccinated \nMay 31\nRisk Interval 1 -21 days post -vaccination21\nJune 3\nVaccinated \nMay 30\n6\n7September: Interim mRNA vaccines safety \nsurveillance, including myocarditis/pericarditis risk \n(JAMA )September: \nBivalent boosters \nPfizer (≥12y) and \nModerna (≥18y)September: Bivalent \nboosters. Monovalent \nboosters discontinuedMay: Pfizer \nmonovalent \nbooster 5 -\n11yMarch: 2nd \nmonovalent \nbooster \n(≥50y)January: \nPfizer \nmonovalent \nbooster\n12-15ySeptember/October: \nAdult monovalent \nbooster; Pfizer \n(≥16y), Moderna and \nJanssen (≥18y)\nOctober: Myocarditis/pericarditis \nrates after primary and monovalent \nboosters <40y ( Ann Int Med )August: Risk of myocarditis/ \npericarditis Pfizer vs Moderna \n(Vaccine )April: GBS following \nJanssen vaccine ( JAMA\nNetwork Open )December: \nEUA Moderna \n(≥18y) and \nPfizer (≥16y)\nNovember/December: first \nVSD signal, ischemic stroke \nafter bivalent Pfizer ≥65y\nOctober: \nBivalent \nboosters Pfizer \n(5-11y) and \nModerna (6 -17y)December: \nBivalent boosters \nPfizer (6m -4y) and \nModerna (6m -5y)May: EUA \nPfizer 12 -\n15y\nMay: \nmyocarditis/\npericarditis \nafter mRNA \nvaccines \nreportedAugust: FDA \napproves \nPfizer (≥16y)\nOctober: \nEUA Pfizer \n5-11y January: FDA \napproves \nModerna \n(≥18y) May 2022: Janssen \nvaccine no longer \nrecommendedJune: EUA Pfizer (6m –4y), \nModerna (6m –17y)\nJuly: EUA \nNovavax \nvaccine (≥18y)2020\nPrimary \nSeries\nMonovalent \nBoosters\nBivalent mRNA \nBoosters\nVSD COVID -19 RCA \nSafety Publications2021 2022 2023\nMarch: >200 \nmillion doses \ngiven in US \nby the end \nAprilApril: \nJanssen \nand CVST \nconcernsFebruary: \nJanssen \nEUA \n(≥18y)\nJune : mRNA \nvaccine safety \n6m-5y (Pediatrics )July: FDA \nsafety \nwarning re: \nGBS and \nJanssen. \n8\n\nResults using vaccinated concurrent \ncomparators\n9\nKlein NP, Lewis N, et. al. JAMA . Published online  September 03, 2021. doi:10.1001/jama.2021.1507210\nOutcomes Monitored Without Comparators\n11\n12\nJAMA . Published online  September 03, 2021. doi:10.1001/jama.2021.15072\nVSD COVID -19 RCA Surveillance:\nOutcomes Monitored Due to Emerging Concerns\n13\n14September: Interim mRNA vaccines safety \nsurveillance, including myocarditis/pericarditis risk \n(JAMA )September: \nBivalent boosters \nPfizer (≥12y) and \nModerna (≥18y)September: Bivalent \nboosters. Monovalent \nboosters discontinuedMay: Pfizer \nmonovalent \nbooster 5 -\n11yMarch: 2nd \nmonovalent \nbooster \n(≥50y)January: \nPfizer \nmonovalent \nbooster\n12-15ySeptember/October: \nAdult monovalent \nbooster; Pfizer \n(≥16y), Moderna and \nJanssen (≥18y)\nOctober: Myocarditis/pericarditis \nrates after primary and monovalent \nboosters <40y ( Ann Int Med )August: Risk of myocarditis/ \npericarditis Pfizer vs Moderna \n(Vaccine )April: GBS following \nJanssen vaccine ( JAMA\nNetwork Open )December: \nEUA Moderna \n(≥18y) and \nPfizer (≥16y)\nNovember/December: first \nVSD signal, ischemic stroke \nafter bivalent Pfizer ≥65y\nOctober: \nBivalent \nboosters Pfizer \n(5-11y) and \nModerna (6 -17y)December: \nBivalent boosters \nPfizer (6m -4y) and \nModerna (6m -5y)May: EUA \nPfizer 12 -\n15y\nMay: \nmyocarditis/\npericarditis \nafter mRNA \nvaccines \nreportedAugust: FDA \napproves \nPfizer (≥16y)\nOctober: \nEUA Pfizer \n5-11y January: FDA \napproves \nModerna \n(≥18y) May 2022: Janssen \nvaccine no longer \nrecommendedJune: EUA Pfizer (6m –4y), \nModerna (6m –17y)\nJuly: EUA \nNovavax \nvaccine (≥18y)2020\nPrimary \nSeries\nMonovalent \nBoosters\nBivalent mRNA \nBoosters\nVSD COVID -19 RCA \nSafety Publications2021 2022 2023\nMarch: >200 \nmillion doses \ngiven in US \nby the end \nAprilApril: \nJanssen \nand CVST \nconcernsFebruary: \nJanssen \nEUA \n(≥18y)\nJune : mRNA \nvaccine safety \n6m-5y (Pediatrics )July: FDA \nsafety \nwarning re: \nGBS and \nJanssen. \nMyocarditis and Pericarditis \nFollowing mRNA Vaccines\n15\nMyocarditis / Pericarditis Among Subgroup \n<40 Years of Age\n17•Chart reviews began May 2021\n•All identified cases of myocarditis/pericarditis during the 98 days after \nvaccination were chart reviewed, followed by infectious disease clinician \nand/or a cardiologist adjudication to:\n•Confirm case was incident following vaccination\n•Met CDC case definition (myocarditis, pericarditis, or myopericarditis)\n•Evaluated level of certainty for myocarditis\nClustering of Confirmed Myocarditis/pericarditis by Days Since Most \nRecent Dose of any mRNA Vaccine Among 12 -39 Year -Olds\n18\nJAMA . Published online  September 03, 2021. doi:10.1001/jama.2021.15072\n19\nKlein NP, Lewis N, et. al. JAMA . Published online  September 03, 2021. doi:10.1001/jama.2021.15072\n•No safety signals for any outcome in the 21 days after both mRNA doses in \nthe overall VSD population, including all ages ≥12 years.\n•In the subgroup aged 12 –39 years, the rate ratio for myocarditis/pericarditis \nwas elevated after both Pfizer and Moderna during days 0 -21 after \nvaccination, and especially during days 0 -7.\n̶In subgroup analyses, both mRNA vaccines were associated with \nmyocarditis/pericarditis in persons aged 12 -39 years. \n•In the VSD, rate of anaphylaxis after mRNA vaccines was ~ 5 cases / million \ndoses.\n•VSD surveillance was ongoing.Summary\n(data through June 2021)\n20\n21September: Interim mRNA vaccines safety \nsurveillance, including myocarditis/pericarditis risk \n(JAMA )September: \nBivalent boosters \nPfizer (≥12y) and \nModerna (≥18y)September: Bivalent \nboosters. Monovalent \nboosters discontinuedMay: Pfizer \nmonovalent \nbooster 5 -\n11yMarch: 2nd \nmonovalent \nbooster \n(≥50y)January: \nPfizer \nmonovalent \nbooster\n12-15ySeptember/October: \nAdult monovalent \nbooster; Pfizer \n(≥16y), Moderna and \nJanssen (≥18y)\nOctober: Myocarditis/pericarditis \nrates after primary and monovalent \nboosters <40y ( Ann Int Med )August: Risk of myocarditis/ \npericarditis Pfizer vs Moderna \n(Vaccine )April: GBS following \nJanssen vaccine ( JAMA\nNetwork Open )December: \nEUA Moderna \n(≥18y) and \nPfizer (≥16y)\nNovember/December: first \nVSD signal, ischemic stroke \nafter bivalent Pfizer ≥65y\nOctober: \nBivalent \nboosters Pfizer \n(5-11y) and \nModerna (6 -17y)December: \nBivalent boosters \nPfizer (6m -4y) and \nModerna (6m -5y)May: EUA \nPfizer 12 -\n15y\nMay: \nmyocarditis/\npericarditis \nafter mRNA \nvaccines \nreportedAugust: FDA \napproves \nPfizer (≥16y)\nOctober: \nEUA Pfizer \n5-11y January: FDA \napproves \nModerna \n(≥18y) May 2022: Janssen \nvaccine no longer \nrecommendedJune: EUA Pfizer (6m –4y), \nModerna (6m –17y)\nJuly: EUA \nNovavax \nvaccine (≥18y)2020\nPrimary \nSeries\nMonovalent \nBoosters\nBivalent mRNA \nBoosters\nVSD COVID -19 RCA \nSafety Publications2021 2022 2023\nMarch: >200 \nmillion doses \ngiven in US \nby the end \nAprilApril: \nJanssen \nand CVST \nconcernsFebruary: \nJanssen \nEUA \n(≥18y)\nJune : mRNA \nvaccine safety \n6m-5y (Pediatrics )July: FDA \nsafety \nwarning re: \nGBS and \nJanssen. \n22Sequential Test1\nOutcome Event in \nRisk \nIntervalAdjusted Rate \nRatio (95% CI)21-sided \nP-value'Signal’ 1 -\nsided p \n<0.0048?\nMyocarditis / \npericarditis 138 1.72 <0.001 YesRCA Signal* for Myocarditis/Pericarditis in the 1 -21 Day Risk \nInterval, all VSD population ≥12 years\nCompared with Outcome Events in Vaccinated Comparators on the Same Calendar Days \n*signal as of August 20211Sequential test requires 1 -sided p < 0.0048 for a signal. This keeps the probability of a false positive signal (due to chance \nalone) below 0.05 in 2 years of surveillance. \n2Adjusted for VSD site, 5 -year age group, sex, race/ethnicity, and calendar date. Comparison interval is 22 –42 days after \neither dose.\n23\n•This study assessed whether the risk of myocarditis/pericarditis \nafter Moderna differs from that after Pfizer\n•We conducted both indirect and direct head -to-head \ncomparisons among 18 –39-year-olds\n24\nVerified Myocarditis and Pericarditis in the 0 -7 Day Risk Interval, among 18 –39-\nYear -Olds by Product and Dose, December 14, 2020 -January 14, 2022\nCompared with Outcome Events in Vaccinated Comparators on the Same Calendar Days \nGoddard, et al. Vaccine .\nHead -to-Head Comparison of Moderna versus Pfizer Regarding Myocarditis and \nPericarditis During Days 0 -7 Day Post -Vaccination in 18 –39-Year -Olds\n25\n➢Risk estimates of myocarditis/pericarditis in 18 –39-year-olds during days 0 -7 \nafter 2 doses were modestly higher after Moderna than after Pfizer.\n26\nGoddard K, et al. .Ann Intern Med . 2022;175:1169 -1771.* Data through August 20, 2022 \nVSD incidence rates of verified myocarditis or pericarditis in the 0 –7 days after mRNA \nvaccination in 5 –39-year-olds, by product, age groups, sex and dose number*\n27September: Interim mRNA vaccines safety \nsurveillance, including myocarditis/pericarditis risk \n(JAMA )September: \nBivalent boosters \nPfizer (≥12y) and \nModerna (≥18y)September: Bivalent \nboosters. Monovalent \nboosters discontinuedMay: Pfizer \nmonovalent \nbooster 5 -\n11yMarch: 2nd \nmonovalent \nbooster \n(≥50y)January: \nPfizer \nmonovalent \nbooster\n12-15ySeptember/October: \nAdult monovalent \nbooster; Pfizer \n(≥16y), Moderna and \nJanssen (≥18y)\nOctober: Myocarditis/pericarditis \nrates after primary and monovalent \nboosters <40y ( Ann Int Med )August: Risk of myocarditis/ \npericarditis Pfizer vs Moderna \n(Vaccine )April: GBS following \nJanssen vaccine ( JAMA\nNetwork Open )December: \nEUA Moderna \n(≥18y) and \nPfizer (≥16y)\nNovember/December: first \nVSD signal, ischemic stroke \nafter bivalent Pfizer ≥65y\nOctober: \nBivalent \nboosters Pfizer \n(5-11y) and \nModerna (6 -17y)December: \nBivalent boosters \nPfizer (6m -4y) and \nModerna (6m -5y)May: EUA \nPfizer 12 -\n15y\nMay: \nmyocarditis/\npericarditis \nafter mRNA \nvaccines \nreportedAugust: FDA \napproves \nPfizer (≥16y)\nOctober: \nEUA Pfizer \n5-11y January: FDA \napproves \nModerna \n(≥18y) May 2022: Janssen \nvaccine no longer \nrecommendedJune: EUA Pfizer (6m –4y), \nModerna (6m –17y)\nJuly: EUA \nNovavax \nvaccine (≥18y)2020\nPrimary \nSeries\nMonovalent \nBoosters\nBivalent mRNA \nBoosters\nVSD COVID -19 RCA \nSafety Publications2021 2022 2023\nMarch: >200 \nmillion doses \ngiven in US \nby the end \nAprilApril: \nJanssen \nand CVST \nconcernsFebruary: \nJanssen \nEUA \n(≥18y)\nJune : mRNA \nvaccine safety \n6m-5y (PediatricsJuly: FDA \nsafety \nwarning re: \nGBS and \nJanssen. \n•Findings were consistent withanassociation between increased riskofGBS and\nJanssen COVID -19vaccine.\n̶When directly compared withmRNA vaccines, t heriskofGBS after Janssen vaccine was21times\nhigher .\n•Noevidence ofassociation between GBS andmRNA -based COVID -19vaccines.\n̶Incidence ofGBS inthe21days after mRNA vaccines wassimilar totheexpected background rate\n̶Nostatistical signals inweekly surveillance withvaccinated concurrent comparators\n•Since publication and through February 2023, VSD identified 5 additional confirmed \ncases of GBS: 4 after mRNA vaccines and 1 after Janssen.\n̶2 were in 1 -21 risk interval (1 mRNA, 1 Janssen), 1 in 22 –42 day interval, and 2 in 43 –84 day interval.\n̶All new cases were among males aged 55 -65 years, except one case in a 4 -year-old male.\n•ACIP preferentially recommended mRNA -based COVID -19vaccines over Janssen\nvaccine in December 2021. (https://www.cdc.gov/mmwr/volumes/71/wr/pdfs/mm7103a4 -H.pdf )\n̶FDA revoked Janssen EUA as of June 2023. (https://www.fda.gov/vaccines -blood -biologics/coronavirus -covid -19-cber -regulated -biologics/janssen -\ncovid -19-vaccine )Summary: Guillain -Barre After COVID -19 Vaccination in the VSD\n28(JAMA Netw Open. 2022;5(4):e228879. https://doi.org/10.1001/jamanetworkopen.2022.8879 )\n29September: Interim mRNA vaccines safety \nsurveillance, including myocarditis/pericarditis risk \n(JAMA )September: \nBivalent boosters \nPfizer (≥12y) and \nModerna (≥18y)September: Bivalent \nboosters. Monovalent \nboosters discontinuedMay: Pfizer \nmonovalent \nbooster 5 -\n11yMarch: 2nd \nmonovalent \nbooster \n(≥50y)January: \nPfizer \nmonovalent \nbooster\n12-15ySeptember/October: \nAdult monovalent \nbooster; Pfizer \n(≥16y), Moderna and \nJanssen (≥18y)\nOctober: Myocarditis/pericarditis \nrates after primary and monovalent \nboosters <40y ( Ann Int Med )August: Risk of myocarditis/ \npericarditis Pfizer vs Moderna \n(Vaccine )April: GBS following \nJanssen vaccine ( JAMA\nNetwork Open )December: \nEUA Moderna \n(≥18y) and \nPfizer (≥16y)\nNovember/December: first \nVSD signal, ischemic stroke \nafter bivalent Pfizer ≥65y\nOctober: \nBivalent \nboosters Pfizer \n(5-11y) and \nModerna (6 -17y)December: \nBivalent boosters \nPfizer (6m -4y) and \nModerna (6m -5y)May: EUA \nPfizer 12 -\n15y\nMay: \nmyocarditis/\npericarditis \nafter mRNA \nvaccines \nreportedAugust: FDA \napproves \nPfizer (≥16y)\nOctober: \nEUA Pfizer \n5-11y January: FDA \napproves \nModerna \n(≥18y) May 2022: Janssen \nvaccine no longer \nrecommendedJune: EUA Pfizer (6m –4y), \nModerna (6m –17y)\nJuly: EUA \nNovavax \nvaccine (≥18y)2020\nPrimary \nSeries\nMonovalent \nBoosters\nBivalent mRNA \nBoosters\nVSD COVID -19 RCA \nSafety Publications2021 2022 2023\nMarch: >200 \nmillion doses \ngiven in US \nby the end \nAprilApril: \nJanssen \nand CVST \nconcernsFebruary: \nJanssen \nEUA \n(≥18y)\nJune : mRNA \nvaccine safety \n6m-5y (Pediatrics )July: FDA \nsafety \nwarning re: \nGBS and \nJanssen. \n30\nMonovalent Booster Uptake Among Persons Aged≥12 Years in the VSD, Over Time* \n* Data through September 10, 2022 when monovalent booster were discontinued in favor of bivalent boosters.  \n\nSummary of RCA Findings in the 1 -21 Day Risk Interval After Monovalent Boosters ≥12 Years\nCompared with Outcome Events 22 -42 Days After in Vaccinated Comparators*\n➢Following mRNA primary series and monovalent booster , only myocarditis/pericarditis met the \nsignaling criteria in the 21 days among ages ≥12 years in the VSD population.Signal?** Signal?**\n*Final analyses through September 2022\n**Signaling threshold P<0.01 (one -sided)\nSignal?** Signal?** Signal?** Signal?** Signal?** Signal?**\n1Comparison interval is 22 –42 days after booster dose.\n2Adjusted for VSD site, 5 -year age group, sex, race/ethnicity, calendar date, and time since primary series.\n3“Either” includes heterologous and homologous primary -> booster doses. Product specific analyses include only homologous primar y->booster doses.\n4One additional case was in the risk interval but not included because there were no appropriate comparators. This case is inc luded in the events/million dose calculation.\n5Two additional cases were in the risk interval but were not included because there were no appropriate comparators. These cas es are included in the events/million dose calculation.Analysis\nAges VaccineEvents \ninRisk\nIntervalEvents in \nComparison \nInterval1Adjusted \nRate Ratio295%\nConfidence\nInterval2-Sided\nP-valueEvents/Million \nDoses\nMonovalent \nBooster312 -17 Pfizer415 4 7.21 2.04 –29.66 0.002 59.9 (34.3 –97.3)\n18–39 Either 22 10 4.46 2.02 –10.37 <0.001 15.8 (9.9 –23.9)\n18–39 Pfizer 11 5 4.81 1.55 –16.81 0.006 14.3 (7.1 –25.5)\n18–39 Moderna56 4 3.27 0.82 –14.23 0.093 16.8 (7.3 –33.1)\n32Verified Myocarditis and Pericarditis in0–7 Days Following \nMonovalent Booster in 12 –39-Year -Olds\nCompared with Events on the Same Calendar Days among Boosted Comparators\n33September: Interim mRNA vaccines safety \nsurveillance, including myocarditis/pericarditis risk \n(JAMA )September: \nBivalent boosters \nPfizer (≥12y) and \nModerna (≥18y)September: Bivalent \nboosters. Monovalent \nboosters discontinuedMay: Pfizer \nmonovalent \nbooster 5 -\n11yMarch: 2nd \nmonovalent \nbooster \n(≥50y)January: \nPfizer \nmonovalent \nbooster\n12-15ySeptember/October: \nAdult monovalent \nbooster; Pfizer \n(≥16y), Moderna and \nJanssen (≥18y)\nOctober: Myocarditis/pericarditis \nrates after primary and monovalent \nboosters <40y ( Ann Int Med )August: Risk of myocarditis/ \npericarditis Pfizer vs Moderna \n(Vaccine )April: GBS following \nJanssen vaccine ( JAMA\nNetwork Open )December: \nEUA Moderna \n(≥18y) and \nPfizer (≥16y)\nNovember/December: first \nVSD signal, ischemic stroke \nafter bivalent Pfizer ≥65y\nOctober: \nBivalent \nboosters Pfizer \n(5-11y) and \nModerna (6 -17y)December: \nBivalent boosters \nPfizer (6m -4y) and \nModerna (6m -5y)May: EUA \nPfizer 12 -\n15y\nMay: \nmyocarditis/\npericarditis \nafter mRNA \nvaccines \nreportedAugust: FDA \napproves \nPfizer (≥16y)\nOctober: \nEUA Pfizer \n5-11y January: FDA \napproves \nModerna \n(≥18y) May 2022: Janssen \nvaccine no longer \nrecommendedJune: EUA Pfizer (6m –4y), \nModerna (6m –17y)\nJuly: EUA \nNovavax \nvaccine (≥18y)2020\nPrimary \nSeries\nMonovalent \nBoosters\nBivalent mRNA \nBoosters\nVSD COVID -19 RCA \nSafety Publications2021 2022 2023\nMarch: >200 \nmillion doses \ngiven in US \nby the end \nAprilApril: \nJanssen \nand CVST \nconcernsFebruary: \nJanssen \nEUA \n(≥18y)\nJune : mRNA \nvaccine safety \n6m-5y (Pediatrics )July: FDA \nsafety \nwarning re: \nGBS and \nJanssen. \n34Primary Series uptake among persons aged 5 -11 years in the VSD, over time* \n* Data through \nFebruary 4, \n2023426,177\n3,122450,217\n2,256\nSummary of RCA Findings in the 1 -21 Day Risk Interval, 5 –11-year-olds\nCompared with Outcome Events 22 -42 days after in Vaccinated Comparators*\nOutcome Both\nEvent Doses\n1 -21 Appendicitis No No No\nBell's palsy No No No\nEncephalitis / myelitis / encephalomyelitis No No No\nStroke, hemorrhagic No No No\nStroke, ischemic No - No\nImmune thrombocytopenia No No No\nKawasaki disease No No No\nMyocarditis / pericarditis No No No\nSeizures No No No\nThrombotic thrombocytopenic purpura No - NoPfizer\nRisk \nInterval \nDaysDose 1 Dose 2\n➢Among children aged 5 -11 years in the VSD, no outcome met the signaling criteria in the \n21 days after primary series vaccination.Signal?** Signal?**\n*Final analyses through January 2023\n**Signaling threshold P<0.061 (one -sided)\n36\n\n37September: Interim mRNA vaccines safety \nsurveillance, including myocarditis/pericarditis risk \n(JAMA )September: \nBivalent boosters \nPfizer (≥12y) and \nModerna (≥18y)September: Bivalent \nboosters. Monovalent \nboosters discontinuedMay: Pfizer \nmonovalent \nbooster 5 -\n11yMarch: 2nd \nmonovalent \nbooster \n(≥50y)January: \nPfizer \nmonovalent \nbooster\n12-15ySeptember/October: \nAdult monovalent \nbooster; Pfizer \n(≥16y), Moderna and \nJanssen (≥18y)\nOctober: Myocarditis/pericarditis \nrates after primary and monovalent \nboosters <40y ( Ann Int Med )August: Risk of myocarditis/ \npericarditis Pfizer vs Moderna \n(Vaccine )April: GBS following \nJanssen vaccine ( JAMA\nNetwork Open )December: \nEUA Moderna \n(≥18y) and \nPfizer (≥16y)\nNovember/December: first \nVSD signal, ischemic stroke \nafter bivalent Pfizer ≥65y\nOctober: \nBivalent \nboosters Pfizer \n(5-11y) and \nModerna (6 -17y)December: \nBivalent boosters \nPfizer (6m -4y) and \nModerna (6m -5y)May: EUA \nPfizer 12 -\n15y\nMay: \nmyocarditis/\npericarditis \nafter mRNA \nvaccines \nreportedAugust: FDA \napproves \nPfizer (≥16y)\nOctober: \nEUA Pfizer \n5-11y January: FDA \napproves \nModerna \n(≥18y) May 2022: Janssen \nvaccine no longer \nrecommendedJune: EUA Pfizer (6m –4y), \nModerna (6m –17y)\nJuly: EUA \nNovavax \nvaccine (≥18y)2020\nPrimary \nSeries\nMonovalent \nBoosters\nBivalent mRNA \nBoosters\nVSD COVID -19 RCA \nSafety Publications2021 2022 2023\nMarch: >200 \nmillion doses \ngiven in US \nby the end \nAprilApril: \nJanssen \nand CVST \nconcernsFebruary: \nJanssen \nEUA \n(≥18y)\nJune : mRNA \nvaccine safety \n6m-5y (Pediatrics )July: FDA \nsafety \nwarning re: \nGBS and \nJanssen. \n38Monovalent Booster Uptake Among Persons Aged5-11 Years in the VSD, Over Time* \n* Data through September 10, 2022 \n\nSummary of RCA Findings in the 1 -21 Day Risk Interval after Monovalent Booster, 5 –11-year-olds\nCompared with Outcome Events 22 -42 days after in Vaccinated Comparators*\n➢Among children aged 5 -11 years in the VSD, no outcome met the signaling criteria in the \n21 days after monovalent booster vaccination. However, vaccine uptake was low.\nSignal?**\n*Final analyses through January 2023\n**Signaling threshold P<0.011 (one -sided)\n40September: Interim mRNA vaccines safety \nsurveillance, including myocarditis/pericarditis risk \n(JAMA )September: \nBivalent boosters \nPfizer (≥12y) and \nModerna (≥18y)September: Bivalent \nboosters. Monovalent \nboosters discontinuedMay: Pfizer \nmonovalent \nbooster 5 -\n11yMarch: 2nd \nmonovalent \nbooster \n(≥50y)January: \nPfizer \nmonovalent \nbooster\n12-15ySeptember/October: \nAdult monovalent \nbooster; Pfizer \n(≥16y), Moderna and \nJanssen (≥18y)\nOctober: Myocarditis/pericarditis \nrates after primary and monovalent \nboosters <40y ( Ann Int Med )August: Risk of myocarditis/ \npericarditis Pfizer vs Moderna \n(Vaccine )April: GBS following \nJanssen vaccine ( JAMA\nNetwork Open )December: \nEUA Moderna \n(≥18y) and \nPfizer (≥16y)\nNovember/December: first \nVSD signal, ischemic stroke \nafter bivalent Pfizer ≥65y\nOctober: \nBivalent \nboosters Pfizer \n(5-11y) and \nModerna (6 -17y)December: \nBivalent boosters \nPfizer (6m -4y) and \nModerna (6m -5y)May: EUA \nPfizer 12 -\n15y\nMay: \nmyocarditis/\npericarditis \nafter mRNA \nvaccines \nreportedAugust: FDA \napproves \nPfizer (≥16y)\nOctober: \nEUA Pfizer \n5-11y January: FDA \napproves \nModerna \n(≥18y) May 2022: Janssen \nvaccine no longer \nrecommendedJune: EUA Pfizer (6m –4y), \nModerna (6m –17y)\nJuly: EUA \nNovavax \nvaccine (≥18y)2020\nPrimary \nSeries\nMonovalent \nBoosters\nBivalent mRNA \nBoosters\nVSD COVID -19 RCA \nSafety Publications2021 2022 2023\nMarch: >200 \nmillion doses \ngiven in US \nby the end \nAprilApril: \nJanssen \nand CVST \nconcernsFebruary: \nJanssen \nEUA \n(≥18y)\nJune : mRNA \nvaccine safety \n6m-5y (PediatricsJuly: FDA \nsafety \nwarning re: \nGBS and \nJanssen. \n41Primary Series Uptake Among Persons Aged≥12 Years in the VSD, Over Time* \n* Data through May 21, 2022Dose 1 Dose 2 Total\nPfizer 4,669,621 4,558,067 9,227,688\nModerna 3,014,353 2,951,499 5,965,852\nJanssen 511,944 NA 511,944\nTotal 8,195,918 7,509,566 15,705,484\nFinal RCA Findings in the 1 -21 Day Risk Interval After Primary Series ≥12 Years\nCompared with Outcome Events 22 -42 days after in Vaccinated Comparators*\n*Final analyses through May 2022\n**Signaling threshold P<0.01 (one -sided)Signal?** Signal?** Signal?** Signal?** Signal?** Signal?** Signal?**\n43September: Interim mRNA vaccines safety \nsurveillance, including myocarditis/pericarditis risk \n(JAMA )September: \nBivalent boosters \nPfizer (≥12y) and \nModerna (≥18y)September: Bivalent \nboosters. Monovalent \nboosters discontinuedMay: Pfizer \nmonovalent \nbooster 5 -\n11yMarch: 2nd \nmonovalent \nbooster \n(≥50y)January: \nPfizer \nmonovalent \nbooster\n12-15ySeptember/October: \nAdult monovalent \nbooster; Pfizer \n(≥16y), Moderna and \nJanssen (≥18y)\nOctober: Myocarditis/pericarditis \nrates after primary and monovalent \nboosters <40y ( Ann Int Med )August: Risk of myocarditis/ \npericarditis Pfizer vs Moderna \n(Vaccine )April: GBS following \nJanssen vaccine ( JAMA\nNetwork Open )December: \nEUA Moderna \n(≥18y) and \nPfizer (≥16y)\nNovember/December: first \nVSD signal, ischemic stroke \nafter bivalent Pfizer ≥65y\nOctober: \nBivalent \nboosters Pfizer \n(5-11y) and \nModerna (6 -17y)December: \nBivalent boosters \nPfizer (6m -4y) and \nModerna (6m -5y)May: EUA \nPfizer 12 -\n15y\nMay: \nmyocarditis/\npericarditis \nafter mRNA \nvaccines \nreportedAugust: FDA \napproves \nPfizer (≥16y)\nOctober: \nEUA Pfizer \n5-11y January: FDA \napproves \nModerna \n(≥18y) May 2022: Janssen \nvaccine no longer \nrecommendedJune: EUA Pfizer (6m –4y), \nModerna (6m –17y)\nJuly: EUA \nNovavax \nvaccine (≥18y)2020\nPrimary \nSeries\nMonovalent \nBoosters\nBivalent mRNA \nBoosters\nVSD COVID -19 RCA \nSafety Publications2021 2022 2023\nMarch: >200 \nmillion doses \ngiven in US \nby the end \nAprilApril: \nJanssen \nand CVST \nconcernsFebruary: \nJanssen \nEUA \n(≥18y)\nJune : mRNA \nvaccine safety \n6m-5y (Pediatrics )July: FDA \nsafety \nwarning re: \nGBS and \nJanssen. \n44Primary Series Uptake Among Persons Aged6 Months -5 Years in the VSD, \nOver Time* \n* Data through March 18, 2023Dose 1 Dose 2 Dose 3 Total\nPfizer 70,580 62,452 30,641 163,673\nModerna 59,872 52,134 NA 112,006\nTotal 130,452 114,586 30,641 275,679\n45RCA in the 1 -21 Day Risk Interval, 6 months -4/5-year-olds \nCompared with Outcome Events 22 -42 days after in Vaccinated Comparators on the Same Calendar Days, June 18, 2022 –March 18, 2023\nGoddard K, Donahue JG, Lewis N, Hanson KE, Weintraub ES, Fireman B, Klein NP. Safety of COVID -19 mRNA Vaccination Among Young Ch ildren in the Vaccine Safety Datalink. Pediatrics. 2023 Jul 1;152(1):e2023061894. doi: 10.1542/peds.2023 -061894.\n46RCA in the 1 -21 Day Risk Interval, 6 months -4/5-year-olds \nCompared with Outcome Events 22 -42 days after in Vaccinated Comparators on the Same Calendar Days, June 18, 2022 –March, 2023\nGoddard K, Donahue JG, Lewis N, Hanson KE, Weintraub ES, Fireman B, Klein NP. Safety of COVID -19 mRNA Vaccination Among Young Ch ildren in the Vaccine Safety Datalink. Pediatrics. 2023 Jul 1;152(1):e2023061894. doi: 10.1542/peds.2023 -061894.•Among children 6 month -4/5 years, no outcome met the signaling \ncriteria in the 21 days after primary series. \n•No cases of myocarditis or pericarditis within the risk interval \n•However, vaccine uptake has been low \n47September: Interim mRNA vaccines safety \nsurveillance, including myocarditis/pericarditis risk \n(JAMA )September: \nBivalent boosters \nPfizer (≥12y) and \nModerna (≥18y)September: Bivalent \nboosters. Monovalent \nboosters discontinuedMay: Pfizer \nmonovalent \nbooster 5 -\n11yMarch: 2nd \nmonovalent \nbooster \n(≥50y)January: \nPfizer \nmonovalent \nbooster\n12-15ySeptember/October: \nAdult monovalent \nbooster; Pfizer \n(≥16y), Moderna and \nJanssen (≥18y)\nOctober: Myocarditis/pericarditis \nrates after primary and monovalent \nboosters <40y ( Ann Int Med )August: Risk of myocarditis/ \npericarditis Pfizer vs Moderna \n(Vaccine )April: GBS following \nJanssen vaccine ( JAMA\nNetwork Open )December: \nEUA Moderna \n(≥18y) and \nPfizer (≥16y)\nNovember/December: first \nVSD signal, ischemic stroke \nafter bivalent Pfizer ≥65y\nOctober: \nBivalent \nboosters Pfizer \n(5-11y) and \nModerna (6 -17y)December: \nBivalent boosters \nPfizer (6m -4y) and \nModerna (6m -5y)May: EUA \nPfizer 12 -\n15y\nMay: \nmyocarditis/\npericarditis \nafter mRNA \nvaccines \nreportedAugust: FDA \napproves \nPfizer (≥16y)\nOctober: \nEUA Pfizer \n5-11y January: FDA \napproves \nModerna \n(≥18y) May 2022: Janssen \nvaccine no longer \nrecommendedJune: EUA Pfizer (6m –4y), \nModerna (6m –17y)\nJuly: EUA \nNovavax \nvaccine (≥18y)2020\nPrimary \nSeries\nMonovalent \nBoosters\nBivalent mRNA \nBoosters\nVSD COVID -19 RCA \nSafety Publications2021 2022 2023\nMarch: >200 \nmillion doses \ngiven in US \nby the end \nAprilApril: \nJanssen \nand CVST \nconcernsFebruary: \nJanssen \nEUA \n(≥18y)\nJune : mRNA \nvaccine safety \n6m-5y (PediatricsJuly: FDA \nsafety \nwarning re: \nGBS and \nJanssen. \n48Bivalent Booster Uptake Among Persons Aged ≥12 Years, Over Time* \n* Data through March 18, 2023\nPfizer -BioNTech\nModerna1,855,946\n851,807\nSummary RCA Findings in the 1 -21 Day Risk Interval after Bivalent Booster 6 months -64 years\nCompared with Outcome Events 22 -42 days after in Vaccinated Comparators*\n*Analyses through March 2023\n**Signaling threshold P<0.01 (one -sided)Signal?** Signal?**Risk Interval \nDaysAge GroupOutcomeEither mRNA Pfizer ModernaEvent\n1 -21 0-4y Kawasaki disease No No -\n5-11y Appendicitis No No -\nBell's palsy No No -\nStroke, hemorrhagic No No -\nImmune thrombocytopenia No No -\nSeizures No No -\n12-17y Appendicitis No No No\nBell's palsy No No -\nEncephalitis / myelitis / encephalomyelitis No No -\nImmune thrombocytopenia No No -\nSeizures No No -\nVenous thromboembolism No No -\n18-64y Acute disseminated encephalomyelitis No No -\nAcute myocardial infarction No No No\nAppendicitis No No No\nBell's palsy No No No\nCerebral venous sinus thrombosis No No No\nDisseminated intravascular coagulation No - No\nEncephalitis / myelitis / encephalomyelitis No No No\nGuillain -Barre syndrome No No -\nStroke, hemorrhagic No No No\nStroke, ischemic No No No\nImmune thrombocytopenia No No No\nMyocarditis / pericarditis No No No\nSeizures No No No\nTransverse myelitis No No -\nThrombotic thrombocytopenic purpura No No No\nThrombosis with thrombocytopenia syndrome No No No\nVenous thromboembolism No No No\nPulmonary embolism (subset of VTE) No No No➢Among ages 5 -64 years in \nthe VSD, no outcomes have \nmet the signaling criteria in \nthe 21 days after bivalent \nbooster vaccine. \n50VSD Incidence Rates of Verified Myocarditis or Pericarditis in the 0 –7 \nDays After Bivalent Booster in Ages 12 –39 years*\nDose 2 primary series \nPfizer -BioNTechMonovalent booster dose \nPfizer -BioNTechBivalent Booster Doses \n(Pfizer and Moderna)\nAge Group \n(yrs)Cases Total\nDose 2 (N)Incidence rate/\nmillion doses\n(95% CI)Cases Total \nDoses \n(N)Incidence rate/\nmillion doses\n(95% CI)Cases Total Doses \n(N)Incidence rate/\nmillion doses\n(95% CI)\nPfizer\n12–17\nMales\nFemales45\n6308,046\n311,247146.1 (106.6 –195.5)\n19.3 (7.1 –42.0)14\n2129,487\n139,118108.1 (59.1 –181.4)\n14.4 (1.7 –51.9)0\n055,649\n57,7760.0 (0.0 –53.8)\n0.0 (0.0 –51.9)\n18–29\nMales\nFemales27\n2331,889\n400,32181.4 (53.6 –118.4)\n5.0 (0.6 –18.0)7\n1166,973\n240,22641.9 (16.9 –86.4)\n4.2 (0.1 –23.2)1\n060,338\n95,16216.6 (0.4 –92.3)\n0.0 (0.0 –31.5)\n30–39\nMales\nFemales5\n3341,527\n410,71314.6 (4.8 –34.2)\n7.3 (1.5 –21.3)3\n1197,554\n268,41215.2 (3.1 –44.4)\n3.7 (0.1 –20.8)0\n097,171\n133,3050.0 (0.0 –30.8)\n0.0 (0.0 –22.5)\nModerna\n18–29\nMales\nFemales19\n0195,809\n243,56097.0 (58.4 –151.5)\n0.0 (0.0 –12.3)7\n1109,337\n156,70764.0 (25.7 –131.9)\n6.4 (0.2 –35.6)0\n022,247\n35,3930.0 (0.0 –134.7)\n0.0 (0.0 –84.6)\n30–39\nMales\nFemales8\n1216,583\n259,78036.9 (15.9 –72.8)\n3.9 (0.1 –21.4)1\n2149,468\n191,7656.7 (0.2 –37.3)\n10.4 (1.3 –37.7)1\n041,820\n55,81623.9 (0.6 –133.2)\n0.0 (0.0 –53.7)\n* Primary series and monovalent booster data through August 20, 2022; ; source: Goddard K, et al. Incidence of Myocarditis/Pericarditis Following mRNA COVID -19 Vaccination Among Children and \nYounger Adults in the United States .Ann Intern Med. 2022;175:1169 -1771 .Bivalent booster data through March 11, 2023\n51September: Interim mRNA vaccines safety \nsurveillance, including myocarditis/pericarditis risk \n(JAMA )September: \nBivalent boosters \nPfizer (≥12y) and \nModerna (≥18y)September: Bivalent \nboosters. Monovalent \nboosters discontinuedMay: Pfizer \nmonovalent \nbooster 5 -\n11yMarch: 2nd \nmonovalent \nbooster \n(≥50y)January: \nPfizer \nmonovalent \nbooster\n12-15ySeptember/October: \nAdult monovalent \nbooster; Pfizer \n(≥16y), Moderna and \nJanssen (≥18y)\nOctober: Myocarditis/pericarditis \nrates after primary and monovalent \nboosters <40y ( Ann Int Med )August: Risk of myocarditis/ \npericarditis Pfizer vs Moderna \n(Vaccine )April: GBS following \nJanssen vaccine ( JAMA\nNetwork Open )December: \nEUA Moderna \n(≥18y) and \nPfizer (≥16y)\nNovember/December: first \nVSD signal, ischemic stroke \nafter bivalent Pfizer ≥65y\nOctober: \nBivalent \nboosters Pfizer \n(5-11y) and \nModerna (6 -17y)December: \nBivalent boosters \nPfizer (6m -4y) and \nModerna (6m -5y)May: EUA \nPfizer 12 -\n15y\nMay: \nmyocarditis/\npericarditis \nafter mRNA \nvaccines \nreportedAugust: FDA \napproves \nPfizer (≥16y)\nOctober: \nEUA Pfizer \n5-11y January: FDA \napproves \nModerna \n(≥18y) May 2022: Janssen \nvaccine no longer \nrecommendedJune: EUA Pfizer (6m –4y), \nModerna (6m –17y)\nJuly: EUA \nNovavax \nvaccine (≥18y)2020\nPrimary \nSeries\nMonovalent \nBoosters\nBivalent mRNA \nBoosters\nVSD COVID -19 RCA \nSafety Publications2021 2022 2023\nMarch: >200 \nmillion doses \ngiven in US \nby the end \nAprilApril: \nJanssen \nand CVST \nconcernsFebruary: \nJanssen \nEUA \n(≥18y)\nJune : mRNA \nvaccine safety \n6m-5y (PediatricsJuly: FDA \nsafety \nwarning re: \nGBS and \nJanssen. \nIschemic Stroke Following Pfizer Bivalent \nBooster Vaccination in 65+ Years of Age\n52\n53Number of COVID -19 Bivalent Booster Doses and Influenza Vaccine Doses \nAdministered Over Time Among Persons Aged ≥65 years, by Vaccine Type\n\nRisk Interval Days Age GroupOutcomeEither mRNA Pfizer ModernaEvent\n1 -21 65+ Acute myocardial infarction No No No\nAppendicitis No No No\nBell's palsy No No No\nCerebral venous sinus thrombosis No No -\nDisseminated intravascular coagulation No No No\nGuillain -Barre syndrome No No No\nStroke, hemorrhagic No No No\nStroke, ischemic Yes Yes No\nImmune thrombocytopenia No No No\nMyocarditis / pericarditis No No No\nSeizures No No No\nThrombotic thrombocytopenic purpura No No No\nThrombosis with thrombocytopenia syndrome No No No\nVenous thromboembolism No No No\nPulmonary embolism (subset of VTE) No No NoSummary RCA Findings in the 1 -21 Day Risk Interval After Bivalent Booster ≥65 years\nCompared with Outcome Events 22 -42 days after in Vaccinated Comparators*\n*Analyses through March 2023\n**Signaling threshold P<0.01 (one -sided)Signal?** Signal?**\n➢Ischemic stroke signaled in the 21 days after bivalent booster vaccine among ≥65 years in the VSD.Signal?**\n55Ischemic Stroke AfterPfizer -BioNTech Bivalent Booster , Age ≥65 years, \nCounts and Adjusted Rate Ratios (Oct 15, 2022 –March 18 , 2023)\nRed dot represents sequential signal: p -value <0.01 (1 -sided)RR= 1.25 (95% CI 0.98 –1.59)\n56Ischemic Stroke by Day after Pfizer -BioNTech Bivalent \nBooster, People Aged ≥65 Years*\nCluster days 13 –22, p -value = 0.0637\n*Data cutoff 2/28/2023\n57Post -Signal analyses*:\nIschemic Stroke Incidence During Days 1 –21 Compared with Days 22 –42, \nAmong ≥65 Years With and Without Simultaneous Influenza Vaccination\nAnalytic populationCases in 1 –21-day\nRisk Interval\n(N=139)Cases in 22 –42-day\nComparison Interval\n(N=108)Adjusted\nRate Ratio**\n(95% CI)P-value \nBivalent Pfizer + same -day\nhigh-dose or adjuvanted \nflu vaccine43 27 1.59 (0.99 –2.61) 0.06\nBivalent Pfizer + same day\nstandard dose flu vaccine8 11 0.73 (0.28 -1.83) 0.50\nBivalent Pfizer without any\nsame day flu vaccine107 99 1.08 (0.82 –1.42) 0.58\n* Analyses only include vaccination data through January 14, 2023, and stroke outcome data through February 25, 2023\n** Adjusted by 5 -year age groups\n58\n\n59Additional Considerations for Stroke Outcome\n▪Small numbers of strokes and imprecise rate ratios limit some analyses \n•Uptake of Moderna booster was delayed and reduced due to distribution delays\n•Follow -up of individuals concurrently given bivalent booster + hi -dose flu was limited by small numbers\n▪Difficult to interpret temporal clustering which attenuated as rate ratio attenuated\n▪Possible unmeasured confounding \n•Results may be influenced by confounders that vary over time\n•Do early adopters of bivalent booster vaccine have greater risk of near -term cardiovascular events? \n‒Same trend has not been observed for acute myocardial infarctions \n‒Potential impact of differential vaccine availability after EUA (Pfizer -BioNTech > Moderna)\n▪Possible role of SARS -CoV-2 infection before booster?\n•Background incidence of SARS -CoV-2 infection was rapidly changing during bivalent booster uptake\n‒Analysis excluded cases with COVID -19 diagnosis or positive test in prior 30 days, although asymptomatic \ninfections and home antigen tests are not consistently documented in EHR; however, KPNC chart reviews did not \nfind recent SARS -CoV-2 infection or exposure\nAnaphylaxis\n•The rate of anaphylaxis was ~ 5 cases/million doses for the mRNA primary series.\n̶The rate of anaphylaxis was <5 cases/million doses for mRNA booster doses. \nMyocarditis/Pericarditis after mRNA vaccines\n•During days 0 -7 post vaccination , both mRNA vaccines were associated with increased risk of \nmyocarditis/pericarditis in 12 –39-year-olds.\n•Risk estimates of myocarditis/pericarditis in 18 –39-year-olds during days 0 -7 after 2 doses were \nmodestly higher after Moderna than after Pfizer.\n•For persons ages 12 –39 years, rates of myocarditis/pericarditis 0 –7 days after primary and \nmonovalent boosters were highest among male 12 -15 and 16 –17-year-olds.\n̶Evidence suggests there was an increased risk for myocarditis/pericarditis following monovalent booster dose for \nsome age groups.\n̶No current evidence for an increased rate of myocarditis/pericarditis following bivalent boosters. Uptake was low in \nage groups expected to be at highest risk. Summary of Safety Findings after COVID -19 Vaccines in the VSD\n60\nIschemic stroke after Pfizer bivalent booster\n•Rate ratio met signaling criteria consistently for 8 weeks but slowly attenuated and now \ndoes not meet signaling criteria\n•Temporal clustering 13 –22 days after vaccination (significant at time of initial signal but \nattenuated as the rate ratio estimate attenuated) \n•Supplemental analyses using un -boosted concurrent comparators showed a rate ratio \nRR=1.07 (95% CI 0.89 –1.28) (data not shown)\n•Analyses evaluating simultaneous high -dose or adjuvanted flu vaccine showed a rate ratio \nRR=1.59 ( 95% CI 0.99 –2.61)\n̶Separate analyses did not detect an elevated RR for stroke after flu vaccine alone (data not shown)\nGBS after Janssen vaccine\n•Findings were consistent withanassociation between increased riskofGBS andJanssen\nCOVID -19vaccine.\n61Summary of Safety Findings After COVID -19 Vaccines in the VSD\nSummary of VSD COVID RCA chart review \n62Vaccine Outcome\nAcute \ndisseminated \nencephalo -\nmyelitis \n(ADEM) \nN=9Anaphylaxis\nN=342Cerebral \nvenous sinus \nthrombosis  \n(CVST) \nN=98Guillain -\nBarré \nsyndrome \n(GBS)  \nN=130Ischemic \nStroke \nN=100Multisystem \nInflammatory \nSyndrome –\nChild/Adult \n(MIS -C/A) \nN=33Myocarditis/\nPericarditis \nN=935Thrombosis \nwith \nthrombo -\ncytopenia \nsyndrome \n(TTS)    \nN=32Transverse \nmyelitis  \n(TM)     \nN=43Venous \nthrombo -\nembolism \n(VTE)    \nN=186TOTAL \nN=1908\nPrimary \nseries \n(mRNA and \nJanssen)9 300 98 130 NR 33 342 \n(6 months -\n39 yrs)32 43 186 1173\nMonovalent \nBooster \n(mRNA) NR 30 NR NR NR NR 362 \n(all ages)NR NR NR 392\nBivalent \nBooster \n(mRNA)NR 12 NR NR 100 \n(65+ yrs)NR 231 \n(all ages)NR NR NR 343\n*Counts are included per individual; however, most outcomes underwent multiple reviews (i.e., quick review, full review, clin ical \nadjudication) \nNR= not reviewed\n1.Vaccine uptake was early & unpredictable. \n̶One rationale for using vaccinated concurrent comparators.\n̶Most RCA findings came early and have been mostly unchanged since fall 2021. \n2.The VSD COVID -19 RCA analytic methods have been hard to understand. \n̶We believe that vaccinated concurrent comparators are less vulnerable to bias, but it is an unfamiliar approach that \nis difficult to explain how the follow up in the comparison interval is concurrent (i.e., on the same calendar day) with \nthe follow up in the risk interval. \n̶However, intense public attention on COVID vaccine safety meant we frequently communicated preliminary results \non short notice, and methods that are hard to concisely explain and understand posed substantial challenges.\n3.Our vaccine safety questions have frequently changed and expanded, requiring us to rapidly \nadapt our surveillance to include new outcomes and age groups. \n̶Flexibility in routinely accommodating (sometime substantial) changes has been critical.\n4.Challenging to digest and interpret the large amounts of potentially relevant data and results \nthat we put “on the shelf” weekly (e.g., comparisons with unvaccinated people).\n̶Supplementary analyses were available should a safety concern arise from VSD or elsewhere. 63Challenges in Rapidly Generating Vaccine Safety Evidence \nDuring the Pandemic\n•2020 -2023 VSD COVID -19 RCA surveillance is complete.\n•Future Studies -VSD may consider further investigating:\n•mRNA vaccine primary series signals of VTE and AMI\n•Bell’s palsy after Janssen primary and mRNA monovalent booster (limited \ndata since neither vaccine is currently available or used)\n•Ischemic stroke after concomitant bivalent boosters and flu vaccines in ≥65 -\nyear-olds in future season \n64Future Considerations \nIt takes a village…\n65\n•Kaiser Permanente Northern California:\n•Ned Lewis, Kristin Goddard, Bruce Fireman, Ousseny Zerbo, Karen Nunley, Pat Ross, Nandini Bahkshi , Laurie \nAukes, Berwick Chan, Arnold Yee, Varun Shah\n•Marshfield Clinic Research Institute:\n•Jim Donahue, Kayla Hanson, Ed Belongia, Tom Boyce, Burney Kieke, Dave McClure, Erica Scotty\n•CDC Immunization Safety Office:\n•Eric Weintraub, Tom Shimabukuro, Matt Oster, Tat’Yana Kenigsberg, Jonathan Duffy, Frank Destefano, Tanya \nMyers \n•VSD Sites\n•HealthPartners Institute, Minneapolis, Minnesota\n•Kaiser Permanente Colorado, Denver, Colorado\n•Kaiser Permanente Northwest, Portland, Oregon\n•Kaiser Permanente Southern California, Los Angeles, California\n•Kaiser Permanente Washington, Seattle, Washington\n•Denver Health, Denver, ColoradoAcknowledgements\n66", "summary": "COVID -19 Vaccine Safety Surveillance: Summary from VSD RCA Nicola Klein, MD, PhD Director, Kaiser Permanente Vaccine Study Center Kaiser Permanente Northern California Advisory Committee in Immunization Practices September 12, 2023  2Vaccine Safety Datalink •Active surveillance: newly licensed vaccines ̶Rapid Cycle Analysis (RCA)  •Evaluate vaccine safety: ̶of new recommendations for existing vaccines ̶for vaccines in high -risk populations, particularly pregnant women  (+ other groups)…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-september-12-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-09-12/07-COVID-Klein-508.pdf", "doc_date": "2023-09-12", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 66}
{"title": "08 COVID Priddy 508", "content": "1\nSafety and Immunogenicity of Moderna COVID -19 \nVaccine (2023 -2024 Formula)\nMonovalent XBB.1.5 Variant Vaccine\nACIP\nSeptember 12, 2023\nFrances Priddy, MD MPH\nModerna\n2\nOutline of Presentation\n▪Overview of clinical trial of XBB.1.5 vaccine\n▪Design \n▪Safety data\n▪Immunogenicity data\n▪Analysis of cross neutralization data for recent variants\n▪Summary\n3\nPhase 2/3 Randomized Safety and Immunogenicity Study \nof XBB.1.5 -Containing Booster in Adults ≥18 Years\nhttps://clinicaltrials.gov/ct2/show/NCT04927065▪Participants previously received 4 doses of COVID -19 vaccine (primary series and booster of \nmRNA -1273 + booster of BA.4/BA.5 vaccine)\n▪Focus of today's presentation will be on the monovalent XBB.1.5 vaccine selected for \n2023 -2024 season\n▪All analyses are descriptive\n+Randomized\nApril 25 -27, \n2023\nN = 101 50 µg XBB.1.5\n25 µg BA.4/5 \n25 µg XBB.1.5N = 51N = 50\nBivalent \nBA.4/5 + XBB.1.5 \n50 μg Monovalent\nXBB.1.5\n50 μg\n4\nDemographics and Baseline Characteristics\nStudy 205J, XBB.1.5 Recipients\nCharacteristicMonovalent\nXBB.1.5 \nN = 50\nMean Age – Years 51.6\nMedian Age – Years (range) 55 (21, 84)\n≥ 65 years 11 (22.0%)\n% Female 30 (60.0%)\nNon-White Race 5 (10.0%)\nMonths between 2nd and 3rd Dose, median (Q1, Q3) 8.2 (7.8, 9.8)\nMonths between 3rd and 4th Dose , median (Q1, Q3) 9.8 (8.3, 10.3)\nMonths between 4th and 5th Dose, median (Q1, Q3) 8.2 (8.1, 8.3)\nPrior SARS -CoV-2 Infection 34 (68.0%)5th Dose (3rd Booster)\n5\nSafety of Moderna COVID -19 Vaccine \n(2023 -2024 Formula) \nXBB.1.5 Monovalent Vaccine\n6\nWithin 7 days of injection ; No Grade 4 events reported\nChalkias et al., medRxiv, 2022, Chu et al, Nat Med 28:1041, 2022 Local Reactions Following Booster Doses in Adults\nStudy 205J and Study 205H, Solicited Safety Set\nParticipants\n(%)68%84% 82%\n4% 5% 5%10%5%8%16%20% 21%\n0%25%50%75%100%\nMono\nXBB.1.5Original Bivalent\nBA.4/5Mono\nXBB.1.5Original Bivalent\nBA.4/5Mono\nXBB.1.5Original Bivalent\nBA.4/5Mono\nXBB.1.5Original Bivalent\nBA.4/5Pain Erythema Swelling Axillary Swelling \nor TendernessGrade 3 Grade 1 -2Original Vaccine\nN = 167Monovalent XBB.1.5\nN = 50Bivalent BA.4/BA.5\nN = 508\nLocal reactions similar or lower than previously authorized Moderna COVID -19 vaccines \n7\nSystemic Reactions Following Booster Doses in Adults \nStudy 205J and Study 205H, Solicited Safety Set\nWithin 7 days of injection ; No Grade 4 events reported\nChalkias et al., medRxiv, 2022, Chu et al, Nat Med 28:1041, 2022 Grade 3 Grade 1 -2Original Vaccine\nN = 167Monovalent XBB.1.5\nN = 50Bivalent BA.4/BA.5\nN = 508\n6% 7%4%34%55%\n49%44%59% 60%\n38%49%46%\n28%41%\n35%\n8%11%14% 14%35%\n22%\n0%25%50%75%100%\nParticipants\n(%)\nHeadache Fatigue Myalgia Arthralgia Nausea / \nVomitingChills Fever\n≥ 38.0ºC (≥100.4ºF)\nSystemic reactions similar or lower than previously authorized Moderna COVID -19 vaccines\n8\nImmunogenicity of  Moderna COVID -19 \nVaccine (2023 -2024 Formula)\nXBB.1.5 Monovalent Vaccine\n9\nRapid Assessment of Neutralization Capacity of \n2023 -2024 XBB.1.5 Vaccine Against Emerging Variants\n▪Pre and post booster sera from XBB.1.5 vaccine recipients assessed against \npreviously dominant and newly emerged variants\n▪Duke assay (Lenti -PsVNA) – Day 29 sera assessed\n▪Moderna research assay (VSV -PsVNA) – Day 15 sera assessed\n▪Titers generally consistent between Day 15 and Day 29\n \n▪Sera tested against:\n▪Prior strains:    Ancestral (D614G), BA.4/BA.5\n▪XBB-lineage:   XBB.1.5, XBB.1.16 \n▪New strains:    EG.5.1, FL.1.5.1, BA.2.86 \nPsVNA – pseudovirus neutralization assay; VSV – vesicular stomatitis virus\nChalkias et al. medRxiv  2023 https://doi.org/10.1101/2023.08.22.23293434\nCorrelation between Duke and Moderna assay described in Choi et al, Nature Medicine https://doi.org/10.1038/s41591 -021-01527 -y\n10\n155221\n7410427113694\n1042 1077\n110100100010000100000\nXBB.1.5 XBB.1.16 EG.5.1 BA.2.86Cross Neutralization Results (Day 29) After XBB.1.5 Vaccine  in \nAdults – Duke Assay\nStudy 205J, Per -Protocol Immunogenicity Set - All Participants\nNeutralizing \nAntibody \nTiter (ID50)\n14.0-fold riseEG.5.1\n16.7-fold riseXBB.1.16Day 29 Pre-Boost\nSubstantial f old rise  demonstrated across newer variants\n17.5-fold riseXBB.1.5\nDay 29 Pre-Boost\nPseudovirus neutralization assay\n10.4-fold riseBA.2.86\nDay 29 Pre-Boost Day 29 Pre-Boost Day 29 Pre-Boost\n11\nCross Neutralization Results (Day 29) After XBB.1.5 Vaccine in \nAdults by Baseline SARS -CoV-2 Serostatus  - Duke Assay\nStudy 205J, Per -Protocol Immunogenicity Set \nCross neutralization demonstrated regardless of prior SARS -CoV-2 infection\nPseudovirus neutralization assay82 134\n43 6015432246\n628 726\n1101001000100001000001000000\n1 2 3 4\n211 27496 1353562 4702\n1331 1304\n1101001000100001000001000000\n1 2 3 4Neutralizing \nAntibody \nTiter (ID50)\nNeutralizing \nAntibody \nTiter (ID50)\nD29 PB\nNo Prior Infection\nPrior Infection\n14.6-fold riseEG.5.1\n13.9-fold rise\n16.7-fold riseXBB.1.16\n17.2-fold riseDay 29 Pre-Boost\n18.8-fold riseXBB.1.5\n16.9-fold rise\n13.1-fold riseBA.2.86\n9.3-fold rise\nD29 PB D29 PB D29 PB\n12\n116144 118931621207 1393 126410571406\n110100100010000100000\n1 2 3 4 5Cross Neutralization Results (Day 15) After XBB.1.5 Vaccine in \nAdults - Moderna Assay\nStudy 205J, Subset Analysis (N = 20)\nConsistent c ross neutralization demonstrated for newer variants, including BA.2.86\nPseudovirus neutralization assay; PB - pre boostNeutralizing \nAntibody \nTiter (ID50)\nD15 PB\n10.7-fold riseEG.5.1\n8.7-fold riseBA.2.86\n11.4-fold riseFL.1.5.1\n9.7-fold riseXBB.1.16\n10.4-fold riseXBB.1.5\nD15 PB D15 PB D15 PB D15 PBDay 15 Pre-Boost\n13\n159 190 142 1322961259 1676 14991157 1600\n1101001000100001000001000000\n1 2 3 4 585 109 9765 8811581158 1065 964 1237\n1101001000100001000001000000\n1 2 3 4 5Neutralizing \nAntibody \nTiter (ID50)\nNeutralizing \nAntibody \nTiter (ID50)\nD15 PB\nNo Prior Infection\nPrior InfectionCross Neutralization Results (Day 15) After XBB.1.5 Vaccine in \nAdults by Baseline SARS -CoV-2 Serostatus  - Moderna Assay\nStudy 205J, Subset Analysis (N=20)\n11-fold riseEG.5.1\n10.5-fold rise\n14-fold riseBA.2.86\n5.4-fold rise\n14.8-fold riseFL.1.5.1\n8.8-fold rise\n10.6-fold riseXBB.1.16\n8.8-fold rise\n13.6-fold riseXBB.1.5\n7.9-fold rise\nD15 PB D15 PB D15 PB D15 PB\nCross neutralization demonstrated regardless of prior SARS -CoV-2 infectionDay 15 Pre-Boost\nPseudovirus neutralization assay\n14\n1151\n123\n162417139961\n3355\n298468\n276148\n110100100010000100000\n1 2 3 4 5 6Cross Neutralization Results (Day 29) in Adults after Bivalent \nBA.4/BA.5 Vaccine \nStudy 205H – Duke Assay\nNeutralizing \nAntibody \nTiter (ID50)Day 29 Pre-Boost\nAncestral \n8.7-fold riseBA.4/BA.5\n27.3-fold riseXBB.1.5\n12.3-fold riseXBB.2.3.2\n15.8-fold riseEG.5\n11.6- fold riseXBB.1.16\n19.3-fold rise\nD29 PB\nLimited cross neutralization to newer variants after previously authorized BA.4/BA.5 bivalent vaccineD29 PB D29 PB D29 PB D29 PB D29 PB\nPseudovirus neutralization assay; PB - pre boost\n15\nSummary\nSafety and Immunogenicity of Moderna COVID -19 Vaccine (2023 -2024 Formula)\nXBB.1.5 Vaccine\nModerna’s \nVaccine \nPreparednessClinical Study  \nof XBB.1.5 \nVaccine\n▪Moderna will supply an XBB.1.5  vaccine  for Fall 2023\n▪Moderna will continue its ongoing variant monitoring and risk \nassessment of emerging variants▪Safety profile of XBB.1.5 vaccine consistent with previously authorized  \nvaccines\n▪Robust neutralizing antibody titers against XBB.1.5, XBB.1.16, EG.5.1, \nFL.1.5.1, and BA.2.86 measured in sera from recipients of XBB.1.5 \nvaccine\n▪XBB.1.5 vaccine is anticipated to be effective against current \nSARS -CoV-2 variants\n16\nTHANK YOU to Our Study Collaborators, \nInvestigators, and Participants\n▪All investigators \n▪Study site personnel\n▪Laboratory personnel \n▪Most importantly, the individuals who participated in these trials", "summary": "1 Safety and Immunogenicity of Moderna COVID -19  Vaccine (2023 -2024 Formula) Monovalent XBB.1.5 Variant Vaccine ACIP September 12, 2023 Frances Priddy, MD MPH Moderna 2 Outline of Presentation ▪Overview of clinical trial of XBB.1.5 vaccine ▪Design  ▪Safety data ▪Immunogenicity data ▪Analysis of cross neutralization data for recent variants ▪Summary 3 Phase 2/3 Randomized Safety and Immunogenicity Study  of XBB.1.5 -Containing Booster in Adults ≥18 Years…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-september-12-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-09-12/08-COVID-Priddy-508.pdf", "doc_date": "2023-09-12", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 16}
{"title": "09 COVID Dubovsky 508", "content": "Data in Support of Novavax XBB.1.5 Vaccine\nDr. Filip Dubovsky , President, Research & Development\nSeptember 12, 2023\n1\nNovavax Vaccine Platform: Recombinant Protein \nParticle Plus Matrix -M™ Adjuvant   \n2Recombinant protein particle\nNative 3-dimensional conformation\nTruncated S. frugiperda glycans \nParticulate structure facilitates antigen \npresentation and processing\nNovavax \n2023- 2024 vaccine\nMatrix -M adjuvant\nInduces robust neutralizing antibodies\nInduces polyfunctional CD4+ Th1 \nNovavax XBB.1.5 Vaccine 2023 -2024 Formulation \nfor Individuals ≥12 years\n•2 vials per carton\n•5 doses per vial\n•0.5 mL dose\n•Ready to use•Stable at 2°C to 8°C\n•9-month shelf life*\n•Use within 12 hours of \nfirst puncturePresentationTransportation & StorageDosing*\n•Single dose for previously vaccinated with any COVID -19 \nvaccine\n•If unvaccinated,2-dose series\n3* FDA review ongoing\nXBB.1.5 Primary Series \nNeutralizing Responses\nNon-human primate data demonstrates Novavax \nvaccine technology induces broadly neutralizing \nantibodies with primary vaccination\n4\nNeutralizing Responses in Macaques: Primary Vaccination with XBB.1.5\nPrimary vaccination induces comparable neutralizing responses to newly emerging variants\n5N = 10; Assay validated for  human samples for Prototype and XBB.1.5\n2 Doses: XBB.1.5 rS\nPrototype XBB.1.5 XBB.2.3 XBB.1.16 XBB.1.16.6 EG.5.1 FL.1.5.1 242628210212214216\nPseudovirus\nNeutralization\n(ID50, GMT)\n95% CI\nLOD\n Variants Pseudovirus\nXBB.1.5 Booster Dose \nNeutralizing Responses\nNeutralizing responses against XBB subvariants \nachieve levels comparable to homologous XBB.1.5 \nresponse\n6\nNeutralizing Responses in Macaques: Primary Vaccination \nBivalent BA.5 Vaccine and Boost with XBB.1.5\nBoosting with XBB.1.5 induces robust neutralizing responses against emerging XBB subvariants\n7 N = 4 -5\nBivalent Primary and XBB.1.5 Booster Dose \nPrototypeXBB.1.5 XBB.2.3XBB.1.16XBB.1.16.6EG.5.1 FL.1.5.1PrototypeXBB.1.5 XBB.2.3XBB.1.16XBB.1.16.6EG.5.1 FL.1.5.12022242628210212214216218\nPseudovirus\nNeutralization\n(ID50, GMT)\n95% CI\nLOD  2 weeks Post XBB.1.5 Boost  5 weeks Pre Booster\n 6.9x      71x    39x      62x    >150x   >150x  >150x\nCellular Immune Responses\nConsistent responses against all variants including \nemerging XBB subvariants\n8\nTh1-Biased CD4+ T Cell Response in Rhesus Macaques \nImmunized with Two Doses of XBB.1.5 Vaccine\nConsistent responses against all variants including emerging XBB subvariants\n9 N = 5 \nPrimary 2 Dose: XBB.1.5 \nPrototypeXBB.1.5\nXBB.1.16.6EG.5.1\nPrototypeXBB.1.5\nXBB.1.16.6EG.5.1\nPrototypeXBB.1.5\nXBB.1.16.6EG.5.1\nPrototypeXBB.1.5\nXBB.1.16.6EG.5.1\nPrototypeXBB.1.5\nXBB.1.16.6EG.5.1100101102103104105\nTh1/Th2\nCytokine+ Cells\n(per 106CD4+\nT cells)\nMeanTh1 Th2\nIFN-γ IL-2 TNF-α IL-5 IL-13\nStimulation rS\nPublic Health Value of Novavax XBB.1.5 Vaccine\n•Only protein -based COVID -19 vaccine in US\n•Non-clinical data supports use of Novavax XBB.1.5 vaccine\n-Induces  robust neutralizing responses against XBB subvariants\n-Generates a polyfunctional Th1 -biased CD4+ cellular immune response \nagainst XBB subvariants\n•Presentation facilitates ease of use\n-Same dose/formulation/vial for all approved indications (0.5mL/dose)\n-Ready to use and refrigerator stable (no mixing, dilution or thawing)\n10", "summary": "Data in Support of Novavax XBB.1.5 Vaccine Dr. Filip Dubovsky , President, Research & Development September 12, 2023 1 Novavax Vaccine Platform: Recombinant Protein  Particle Plus Matrix -M™ Adjuvant    2Recombinant protein particle Native 3-dimensional conformation Truncated S. frugiperda glycans  Particulate structure facilitates antigen  presentation and processing Novavax  2023- 2024 vaccine Matrix -M adjuvant Induces robust neutralizing antibodies Induces polyfunctional CD4+ Th1 …", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-september-12-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-09-12/09-COVID-Dubovsky-508.pdf", "doc_date": "2023-09-12", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 10}
{"title": "10 COVID Modjarrad 508", "content": "1 Breakthroughs that change patients’ lives Monovalent XBB.1.5 BNT162b2 COVID-19 Vaccine \nACIP Presentation September 12, 2023 \nCC-2Presentation Outline \nKayvon Modjarrad, M.D., Ph.D. \nExecutive Director, Viral Vaccines \nVaccine Research and Development, Pfizer Inc. Variant Epidemiology \nCOVID-19 Updated Vaccine \nApproval Pathway \nMonovalent XBB.1.5 BNT162b2 \nVaccine Activity Against \nContemporary Omicron Sublineages \nClinical Update \n\nCC-3XBB Sublineages Continue to Dominate the Epidemiolo gic \nLandscape, Despite the Emergence of New Lineages \nGrowing Dominance of EG.5.1 \nSource: 3D Spike Model - Pfizer \nMutation Prediction - jbloomlab.github.io/SARS2-RBD-escape-calc Source: GISAID - gisaid.org , data accessed/analyzed in Pizer, September 08, 20 23 \nBA.2.86 has high mutational density in Spike \nprotein but accounts for <1% of cases \n\nCC-4Pathway for COVID-19 Variant-Adapted Vaccine Update s \nCOVID-19 \nVaccine \nDevelopment Early-stage development \n“at risk” and  \nsurveillance to inform \nvariant selection Manufacture (pre-clinical \nand CMC data), Regulatory \nSubmissions and Review Distribute Vaccines Strain Selection FDA Authorization/Approval \nACIP Recommendation \n• In accordance with FDA guidance for licensure, pre clinical/CMC \ndata package submission and review help ensure time ly \navailability of seasonal variant-matched vaccine, s imilar to the \nmodel for annual influenza vaccine updates. \nCC-5Clinical and Preclinical Experience with Variant-mo dified Vaccines –\nSupported Bivalent BA.4/5 Vaccine Authorization \nPreclinical Data Clinical Data Vaccine Regimen Age Group Modified Vaccine Beta monovalent Omicron BA.1 monovalent Omicron BA.1 bivalent Omicron BA.4/5 bivalent \nOngoing Single Dose 12 to 55 years \n>55 years Omicron XBB.1.5 monovalent \n18 to 55 years \n18 to 55 years \n18 to 55 years \n>55 years \n6 months to 11 years \n12 to 55 years \n>55 years \nOriginal Vaccine \n Variant Vaccine \n\nCC-6Booster Vaccination Study Design \nFemale Balb/c mice (10 per group) were experienced with a primary series of monovalent BNT162b2 Origin al vaccine and a 3 rd booster dose of \nbivalent BNT162b2 (Original+BA.4/5) vaccine. Mice t hen received a 4 th booster dose of either a bivalent BNT162b2 (Origina l+BA.4/5) or a monovalent \nBNT162b2 (XBB.1.5) vaccine. \nData were generated by same pseudovirus neutralizat ion assay and from sera of same mouse study present ed at VRBPAC June 15, 2023 meeting \n(https://www.fda.gov/media/169541/download ). \nData on file: Pfizer-BioNTech. September 2023. Blood sample \n Vaccination \n0 21 105 134 Day: 160 \nMonovalent \nOriginal Monovalent \nOriginal Bivalent \nOriginal+BA.4/5 Bivalent \nOriginal+BA.4/5 \nMonovalent \nXBB.1.5 \n\nCC-7Monovalent XBB.1.5 BNT162b2 Booster Vaccine Effectiv ely Neutralized \nPredominant and Emerging Variants \nData were generated by the same pseudovirus neutral ization assay and from sera of same mouse study tha t generated data that were presented at VRBPAC June 15, 2023 Meeting ( https://www.fda.gov/media/169541/download ). \n50% Neutralization Titers are Geometric Mean Titers  of 10 mice per vaccine group. LOD, limit of detect ion; the lowest serum dilution of 1:20. \n\nCC-8Monovalent XBB.1.5 BNT162b2 Booster Vaccine Elicite d Substantially Higher \nNeutralizing Response Compared to the Bivalent Vacc ine \nData were generated by same pseudovirus neutralizat ion assay and from sera of same mouse study that ge nerated data that were presented at VRBPAC June 15,  2023 Meeting ( https://www.fda.gov/media/169541/download ). \nGMR = Geometric Mean Ratio of the Geometric Mean Ti ter (GMT) of Monovalent XBB.1.5 divided by GMT of W T+BA.4/5 group.  LOD, limit of detection; the lowes t serum dilution of 1:20. \n/uni0047/uni004D/uni0052/uni0020/uni0028/uni0072/uni0065/uni006C/uni0061/uni0074/uni0069/uni0076/uni0065/uni0020/uni0074/uni006F/uni0020/uni004F/uni0072/uni0069/uni0067/uni0069/uni006E/uni0061/uni006C/uni0020/uni002B/uni0020/uni0042/uni0041/uni002E/uni0034/uni002F/uni0035/uni0029\n\nCC-9Blood sample \n Vaccination \n0 21 49 Day: \nBivalent \n(Original/BA.4/5) \nMonovalent \nXBB.1.5 \nBivalent \n(Original/BA.4/5) \nMonovalent \nXBB.1.5 Primary Series Study Design \nFemale Balb/c mice (10 per group) were administered  2 doses (21 days apart) of either bivalent BNT162b 2 (Original+BA.4/5) or monovalent \nBNT162b2 (XBB.1.5) vaccine. \nData were generated by same pseudovirus neutralizat ion assay and from sera of same mouse study present ed at VRBPAC June 15, 2023 meeting \n(https://www.fda.gov/media/169541/download ). \nData on file: Pfizer-BioNTech. September 2023. \nCC-10These data were generated by same pseudovirus neutr alization assay and from sera of same mouse study t hat generated data that were presented at VRBPAC Jun e 15, 2023 Meeting ( https://www.fda.gov/media/169541/download ). \n50% Neutralization Titers are Geometric Mean Titers  of 10 mice per vaccine group. \nLOD, limit of detection; the lowest serum dilution of 1:20. Monovalent XBB.1.5 BNT162b2 Primary Series Effectiv ely Neutralized \nEG.5.1 and XBB.1.5 \n\nCC-11Monovalent XBB.1.5 BNT162b2 Primary Series Elicited  Substantially Higher \nNeutralizing Response Compared to the Bivalent Vacc ine \nThese data were generated by same pseudovirus neutr alization assay and from sera of same mouse study t hat generated data that were presented at VRBPAC Jun e 15, 2023 Meeting ( https://www.fda.gov/media/169541/download ). \nGMR = Geometric Mean Ratio of the Geometric Mean Ti ter (GMT) of Monovalent XBB.1.5 and Bivalent XBB.1. 5+BA.4/5 divided by GMT of WT+BA.4/5 group.  \nLOD, limit of detection; the lowest serum dilution of 1:20. \n\nCC-12Monovalent XBB.1.5 BNT162b2 Clinical Study in Individuals ≥ 12 years \nMonovalent XBB.1.5 BNT162b2 30µg \nGroup 1 (n=200): 12- 55 years \nGroup 2 (n=200): >55 years \nCC-13• The SARS-CoV-2 epidemiologic landscape remains dom inated by XBB \nsublineages. \n• Monovalent XBB.1.5 BNT162b2 is equally immunogenic  against XBB.1.5, \nEG.5.1 and BA.2.86, in a COVID-19 vaccine-experienc ed preclinical study. \n• Variant-adapted vaccines improve immune responses against antigenically \nmatched and closely related strains. \n• A preclinical/CMC package for variant-adapted COVI D-19 vaccine fulfilled \nlicensure criteria. Summary \n14 Breakthroughs that change patients’ lives Monovalent XBB.1.5 Pfizer-BioNTech COVID-19 Vaccine \nACIP September 12, 2023", "summary": "1 Breakthroughs that change patients’ lives Monovalent XBB.1.5 BNT162b2 COVID-19 Vaccine  ACIP Presentation September 12, 2023  CC-2Presentation Outline  Kayvon Modjarrad, M.D., Ph.D.  Executive Director, Viral Vaccines  Vaccine Research and Development, Pfizer Inc. Variant Epidemiology  COVID-19 Updated Vaccine  Approval Pathway  Monovalent XBB.1.5 BNT162b2  Vaccine Activity Against  Contemporary Omicron Sublineages  Clinical Update   CC-3XBB Sublineages Continue to Dominate the Epidemiolo…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-september-12-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-09-12/10-COVID-Modjarrad-508.pdf", "doc_date": "2023-09-12", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 14}
{"title": "11 COVID Wallace 508", "content": "Centers for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nEvidence to Recommendations Framework:\n2023 –2024 (Monovalent, XBB Containing) COVID -19 Vaccine\nMegan Wallace, DrPH, MPH\nACIP Meeting \nSeptember 12, 2023\nEvidence to Recommendations Framework \n▪Structure to describe information considered in moving from evidence to ACIP vaccine \nrecommendations\n▪Provide transparency around the impact of additional factors on deliberations when \nconsidering a recommendation Evidence to Recommendations ( EtR) Framework \n3\n44Evidence to Recommendations (EtR) Framework \nEtR Domain Question(s)\nPublic Health Problem •Is the problem of public health importance?\nBenefits and Harms•How substantial are the desirable anticipated effects?\n•How substantial are the undesirable anticipated effects?\n•Do the desirable effects outweigh the undesirable effects?\nValues•Does the target population feel the desirable effects are large relative to \nthe undesirable effects?\n•Is there important variability in how patients value the outcome?\nAcceptability •Is the intervention acceptable to key stakeholders?\nFeasibility •Is the intervention feasible to implement?\nResource Use •Is the intervention a reasonable and efficient allocation of resources?\nEquity •What would be the impact of the intervention on health equity?\n55Evidence to Recommendations (EtR) Framework \nEtR Domain Question(s) Domain Equity Question(s)\nPublic Health \nProblem•Is the problem of public health importance? •Does the problem impact all populations equally?\nBenefits and \nHarms•How substantial are the desirable anticipated effects?\n•How substantial are the undesirable anticipated effects?\n•Do the desirable effects outweigh the undesirable \neffects?•Are the desirable and undesirable anticipated effects \ndemonstrated across all populations equally?\nValues•Does the target population feel the desirable effects are \nlarge relative to the undesirable effects?\n•Is there important variability in how patients value the \noutcome?•Is there important variability in how patients or \npopulations value the outcome?\nAcceptability •Is the intervention acceptable to key stakeholders?•Is the intervention equally acceptable across all \npopulations?\nFeasibility •Is the intervention feasible to implement?•Is the intervention equally feasible to implement across \nall populations?\nResource Use•Is the intervention a reasonable and efficient allocation \nof resources?•Is the intervention a reasonable and efficient allocation \nof resources across all populations?\nThe intervention = 2023 –2024 (monovalent, XBB containing) COVID -19 vaccine \nThe problem = COVID -19 \n▪Should 2023 -2024 (monovalent, XBB containing) COVID -19 vaccines authorized under \nEUA or approved by BLA be recommended for use in persons ≥6 months of age?\nProducts and ages currently authorized or approved by FDA include:\n▪Moderna COVID -19 vaccine for ages 6 months and older\n▪Pfizer -BioNTech COVID -19 vaccine for ages 6 months and older\nProducts and ages under review for authorization or approval by FDA include:\n▪Novavax COVID -19 vaccine for ages 12 years and olderEvidence to Recommendations ( EtR) Framework\nPolicy Question\n6 EUA: Emergency Use Authorization; BLA: Biologics License Application\n7Bivalent COVID -19 vaccine recommendations for mRNA \nCOVID -19 vaccines\n≥5/6 years6 months –4/5 years2 doses \nModerna3 doses \nPfizer -\nBioNTechOR1 dose \nModerna1 dose \nPfizer -\nBioNTechOR Unvaccinated\nPreviously \nvaccinated\n≥6 months1 dose \nModerna1 dose \nPfizer -\nBioNTechOR\nNote: Those ages 6 months –4 years who have previously received a single dose of Pfizer -BioNTech would need 2 additional doses. Additional doses are recommended for persons with \nimmunocompromising conditions.\n8Proposed 2023 –2024 COVID -19 vaccine recommendations \nfor mRNA COVID -19 vaccines\n≥ 5 years 6 months –4 years2 doses \nModerna3 doses \nPfizer -\nBioNTechOR1 dose \nModerna1 dose \nPfizer -\nBioNTechOR Unvaccinated\nPreviously \nvaccinated\n≥6 months1 dose \nModerna1 dose \nPfizer -\nBioNTechOR\nNote: Those ages 6 months –4 years who have previously received a single dose of Pfizer -BioNTech would need 2 additional doses. Additional doses are recommended for persons with \nimmunocompromising conditions.\n▪The original Novavax COVID -19 vaccine remains authorized for use as a 2 -dose primary \nseries \n▪The original Novavax COVID -19 vaccine can be given as booster dose in limited \nsituations to \n–People ages 18 years and older who previously completed primary vaccination using \nany FDA -approved or FDA -authorized COVID -19 vaccine\n–Have not received any previous booster dose(s) \n–Are unable (i.e., mRNA vaccine contraindicated or vaccine not available) or unwilling \nto receive an mRNA vaccine and would otherwise not receive a booster dose\n▪Authorizations or approvals for 2023 –2024 Novavax COVID -19 vaccine will be \ndetermined by FDA with CDC recommendations to followCurrent recommendations for Novavax COVID -19 vaccine\n9\n▪Updated COVID -19 vaccine referred to as the “2023 –2024 COVID -19 vaccine” in this \npresentation\n▪Following ACIP meeting, both “updated COVID -19 vaccine” and “2023 –2024 COVID -19 \nvaccine” will be used to refer to the monovalent XBB.1.5 containing vaccinesCOVID -19 vaccine nomenclature \n10\nEtRDomain:\nPublic Health Problem \n\nWeekly Population -Based Rates of COVID -19-Associated \nHospitalizations —COVID -NET, March 2020 –August 26,  \n2023\n020406080100120140\n3/7/2020\n5/7/2020\n7/7/2020\n9/7/2020\n11/7/2020\n1/7/2021\n3/7/2021\n5/7/2021\n7/7/2021\n9/7/2021\n11/7/2021\n1/7/2022\n3/7/2022\n5/7/2022\n7/7/2022\n9/7/2022\n11/7/2022\n1/7/2023\n3/7/2023\n5/7/2023\n7/7/2023Rate per 100,000 population\nWeek Ending DateMarch 1, 2020 –August 26, 2023\n<6 months 6 months –4 years 5–11 years 12–17 years\n18–49 years 50–64 years 65–74 years ≥75 years020406080100120140Rate per 100,000 population\nWeek Ending DateJanuary 1 –August 26, 2023\nGray boxes indicate potential reporting delays. Interpretation of trends should be excluded from these weeks. Rates highest in ≥75 years, followed by \ninfants <6 months and adults 65 –74 years\n12\n13COVID -19 new hospital admissions, by week, in the United States \nNational Healthcare Safety Network (NHSN), August 2020 –August 2023\nSource: COVID -19–associated hospitalization data reported to CDC’s National Healthcare Safety Network (NHSN). \nhttps://covid.cdc.gov/covid -data -tracker/#trends_weeklyhospitaladmissions_select_00\n\n1414Other pediatric vaccine preventable diseases: Annual hospitalizations per \n100,000 population prior to recommended vaccines compared to COVID -19 \n1 https://www.cdc.gov/mmwr/preview/mmwrhtml/ss5603a1.htm\n2Davis MM, Patel MS, Gebremariam A. Decline in varicella -related hospitalizations and expenditures for children and adults after introduction of varicella vacci ne in the United \nStates. Pediatrics. 2004;114(3):786 -792. doi:10.1542/peds.2004 -0012\n3Centers for Disease Control and Prevention (CDC). Direct and indirect effects of routine vaccination of children with 7 -valent pneumococcal conjugate vaccine on incidence of \ninvasive pneumococcal disease --United States, 1998 -2003. MMWR Morb Mortal Wkly Rep. 2005 Sep 16;54(36):893 -7. PMID: 16163262.\n4COVID -NET data October 2021 –September 2022 and October 2022 –July 2023. COVID -19 rates have not been adjusted for reason for admission. COVID vaccine first introduced \nin 12 -17 years in May 2021; in 5 -11 years in November 2021 and in 6 months –4 years in June 2022Hepatitis A1 Varicella2\n(Chickenpox)Vaccine -type \nInvasive \nPneumococcal \nDisease3COVID -194\nAge 5–14 years 0–4 years 0–4 years 6 months –<18 years\nTime period 2005 1993 –1995 1998 –19992021 –2022\n2022 –2023\nHospitalization \nBurden\n(Annual rate per \n100,000 population)<1 29-42 405≤4 years: 92 –220\n5–11 years : 15–47\n12–17 years: 20 –80\n1515COVID -19 Scenario Modeling Hub\nhttps://covid19scenariomodelinghub.org/▪A multi -team effort aimed at creating and modeling planning scenarios of the mid -to \nlong -term COVID -19 situation\n▪Scenarios developed in close collaboration with government agencies and other \nstakeholders \n▪Project hospitalizations and deaths\n\n1616Assumptions of COVID -19 Scenario Modeling Hub Round 17\n1. Low immune escape: immune escape occurs at a constant rate of 20% per year; high immune escape: immune escape occurs at a constant rate of 50% per year▪Sixscenarios focusing on three vaccine recommendation scenarios and two different \nrates of immune escape\n–No vaccine recommendation vsrecommendation for 65+ years vsuniversal \nrecommendation\n–Low immune escape vs high immune escape1\n▪Assumed vaccines reformulated to target strains circulating on June 15thof each year, \nmade available September 1\n▪Reformulated vaccines assumed to have 65% VE against symptomatic infection with the \nstrain targeted by reformulation\n▪Vaccine uptake based on first booster uptake (September 2021) \n▪Teams required to project a minimum of 2 years into the future\n▪Eight teams provided national level projections\n1717Based on ensemble projections, weekly hospitalizations are likely to \nincrease this winter and stay within last year’s range\nhttps://covid19scenariomodelinghub.org/\n\n1818People ages 6 months –49 years with no underlying conditions are still \nadmitted to the ICU with COVID -19\nCOVID -NET: Underlying Medical Conditions among Patients Admitted to ICU among Children, Adolescents, \nand Adults Ages 6 Months –49 Years, July 2022 –June 2023\n•Relative standard errors >30%; estimates might be unstable due to small sample size\n•Limited to COVID -NET hospitalizations with COVID -19-related illness as likely reason for admissionAge category% with no \nunderlying \nconditionsOf those with no \nunderlying \nconditions, what % \nwere admitted to \nICU?\n6–23 months 57% 27%\n2–4 years 39% 19%\n5–11 years 24% 23%\n12–17 years 25% 31%\n18–49 years 16% 15%% admitted to ICU \nwith no \nunderlying \nconditions\n53%\n32%\n24%\n22%\n13%\n19Provisional COVID -19 deaths, by week, in the United States, \nreported to CDC\nThe most recent 3 weeks of mortality counts are shaded grey because NVSS reporting is <95% during this period.\nSource: Provisional Deaths from the CDC’s National Center for Health Statistics (NCHS) National Vital Statistics System (NVSS ). https://covid.cdc.gov/covid -data -\ntracker/#trends_weeklydeaths_weeklydeathrateaa_00\n\n20COVID -19-associated deaths in persons ages ≥20 years (by underlying \ncause of death), by age group and year –National Vital Statistics System\n1Provisional data\n2Partial data\nSource: Centers for Disease Control and Prevention, National Center for Health Statistics. National Vital Statistics System, Provisional Mortality on CDC WONDER Online Database. \nData are from the final Multiple Cause of Death Files, 2018 -2021, and from provisional data for years 2022 -2023, as compiled fro m data provided by the 57 vital statistics \njurisdictions through the Vital Statistics Cooperative Program. Number of deaths includes COVID -19 code (U07.1) as the underlyin g cause of death. Accessed at \nhttp://wonder.cdc.gov/mcd -icd10 -provisional.html on Aug 25, 2023 4:53:59 PM871659,054282,836\n23,189110,606282,457\n576433,895146,255\n451 282124,776\n050000100000150000200000250000300000\n20-44 years 45-64 years 65+ years 20-44 years 45-64 years 65+ years 20-44 years 45-64 years 65+ years 20-44 years 45-64 years 65+ years\n2020 2021 2022 Jan 1 - July 22, 2023Number of Deaths\n1\n21COVID -19-associated deaths in persons ages ≤19 years (by underlying \ncause of death), by age group and year –National Vital Statistics System\n1Provisional data\n2Partial data\nSource: Centers for Disease Control and Prevention, National Center for Health Statistics. National Vital Statistics System, Provisional Mortality on CDC WONDER Online Database. \nData are from the final Multiple Cause of Death Files, 2018 -2021, and from provisional data for years 2022 -2023, as compiled fro m data provided by the 57 vital statistics \njurisdictions through the Vital Statistics Cooperative Program. Number of deaths includes influenza codes (J09 -J11) or COVID -19 code (U07.1) as the underlying cause of death. \nAccessed at http://wonder.cdc.gov/mcd -icd10 -provisional.html on Aug 25, 2023 4:53:59 PM3519167\n91\n54493\n156\n101292\n261836\n0100200300400500600\n<1 year 1-4 years 5-19 years <1 year 1-4 years 5-19 years <1 year 1-4 years 5-19 years <1 year 1-4 years 5-19 years\n2020 2021 2022 Jan 1 - July 22, 2023Number of Deaths\n1\n22Among children ≤17 years who died in -hospital, 50% had no underlying \nconditions\nCOVID -NET: Underlying Medical Conditions among Patients with In -Hospital Death among \nChildren and Adolescents Ages ≤17 Years, January 2022 –June 2023\nLimited to COVID -NET hospitalizations with COVID -19-related illness as likely reason for admission\n* Relative standard error >30; indicates estimate might be unstable due to low sample size (n=24).Age category% with no \nunderlying \nconditionsOf those with no \nunderlying \nconditions, what % \ndied in -hospital?\n≤17 years 51% 1%*% of those who died \nin-hospital with no \nunderlying \nconditions\n50%\n231Vogt TM , Wise ME, Bell BP , Finelli L. Declining hepatitis A mortality in the United States during the era of hepatitis A vaccination. J Infect Dis2008; 197:1282 –8.\n2National Notifiable Diseases Surveillance System with additional serogroup and outcome data from Enhanced Meningococcal Disea se Surveillance for 2015 -2019.\n3Meyer PA, Seward JF, Jumaan AO, Wharton M. Varicella mortality: trends before vaccine licensure in the United States, 1970 -1994. J Infect Dis. 2000;182(2): 383-390. \ndoi:10.1086/315714\n4Roush SW , Murphy TV; Historical comparisons of morbidity and mortality for vaccine -preventable diseases in the United States. J AMA 2007; 298:2155 –63.\n5 Glass RI, Kilgore PE, Holman RC, et al. The epidemiology of rotavirus diarrhea in the United States: surveillance and estimat es of disease burden. J Infect Dis. 1996 Sep;174 Suppl 1:S5 -11\n6 http://wonder.cdc.gov/mcd -icd10 -provisional.html on Aug 1, 2023 . COVID vaccine first introduced in 12 -17 years in May 2021; in 5 -11 years in November 2021 and in 6 months –4 \nyears in June 2022Pediatric vaccine preventable diseases: Deaths per year in the United \nStates prior to recommended vaccines compared to COVID -19\nHepatitis A1Meningococcal \n(ACWY)2 Varicella3 Rubella4 Rotavirus5 COVID -196\nAge <20 years 11–18 years 5–9 years All ages <5 years 6 months –<18 years\nTime \nperiod1990 –1995 2000 –2004 1990 –1994 1966 –1968 1985 –1991 2022\nAverage \ndeaths \nper year3 8 16 17 20≤1year: 156\n1–4 years : 101\n5–19 years:292\n24COVID -19and Influenza -associated deaths in persons ages ≤19 years (by \nunderlying cause of death), by age group and year –National Vital Statistics \nSystem\n1Provisional data\n2Partial data\nSource: Centers for Disease Control and Prevention, National Center for Health Statistics. National Vital Statistics System, Provisional Mortality on CDC WONDER Online Database. \nData are from the final Multiple Cause of Death Files, 2018 -2021, and from provisional data for years 2022 -2023, as compiled fro m data provided by the 57 vital statistics \njurisdictions through the Vital Statistics Cooperative Program. Number of deaths includes influenza codes (J09 -J11) or COVID -19 code (U07.1) as the underlying cause of death. \nAccessed at http://wonder.cdc.gov/mcd -icd10 -provisional.html on Aug 25, 2023 4:53:59 PM3519167\n91\n54493\n156\n101292\n26 1836144896\n0 0 01254103\n018 10\n0100200300400500600\n<1 year 1-4 years 5-19 years <1 year 1-4 years 5-19 years <1 year 1-4 years 5-19 years <1 year 1-4 years 5-19 years\n2020 2021 2022 Jan 1 - July 22, 2023Number of Deaths\nCOVID Influenza1\nDomain Equity Question:\nDoes the problem impact all populations equally?\n\n2626Age -adjusted COVID -19-associated hospitalization rates by \nrace and ethnicity*  —COVID -NET, October 2022 –August \n2023\n* Black, White, American Indian/Alaska Native and Asian/Pacific Islander people were categorized as non -Hispanic; Hispanic peopl e \ncould be of any race. Cumulative hospitalization rates remain highest in \nAmerican Indian/Alaska Native and Black persons\nSource: COVID -NET: https://www.cdc.gov/coronavirus/2019 -ncov/covid -data/covid -net/purpose -methods.html . Data March 1, 2020 through August 26, 2023. 0246810121416\n1/7/2023 2/7/2023 3/7/2023 4/7/2023 5/7/2023 6/7/2023 7/7/2023 8/7/2023Rates per 100,000 population3-week moving average rate \nJanuary –August 2023\nWhite Black Asian/Pacific Islander American Indian/Alaskan Native Hispanic050100150200250300350Rates per 100,000 Cumulative rates \nOctober 2022 –August 2023\n2727\nRisk ratio of death, invasive mechanical ventilation (IMV), and admission to intensive \ncare unit (ICU), by the number of underlying medical conditions among adults \nhospitalized with COVID -19, March 2020 –March 2021\nKompaniyets L, Pennington AF, Goodman AB, Rosenblum HG, Belay B, Ko JY , et al. Underlying Medical Conditions and Severe Illness Among 540 ,667 Adults Hospitalized With COVID -\n19, March 2020 –March 2021. Prev Chronic Dis 2021;18:210123. DOI: http://dx.doi.org/10.5888/pcd18.210123\n2828Prevalence of any \ncondition:Selected chronic conditions by U.S. county, 2018\nBased on Razzaghi H, Wang Y, Lu H, Marshall KE, Dowling NF, Paz -Bailey G,Twentyman ER, Peacock G, Greenlund KJ, Estimated County -Level Prevalence of Selected Underlying Medical Conditions \nAssociated with Increased Risk for Severe COVID -19 Illness -United States, 2018 MMWR Morb Mortal Wkly Rep 2020;69[945 -950]. The underlying medical conditions included in these prevalence \nestimates were selected using a subset of the list of conditions with the strongest and most consistent evidence of associati on with increased risk for severe COVID -19-associated illness on CDC’s website \nas of June 25, 2020 and for which questions on the BRFSS are available. https://covid.cdc.gov/covid -data -tracker/#underlying -med -conditions\n(%)\n2929Number of chronic conditions by age among Asian, Black, Latino/Hispanic, \nand White adults in the National Health Interview Survey, 1999 to 2018\nSource: Caraballo C, Herrin J, \nMahajan S, et al. Temporal Trends in \nRacial and Ethnic Disparities in \nMultimorbidity Prevalence in the \nUnited States, 1999 -2018. Am J Med . \n2022;135(9):1083 -1092.e14. \ndoi:10.1016/j.amjmed.2022.04.010  \n\n▪COVID -19 burden is currently lower than at previous points in the pandemic, however the \nabsolute number of hospitalizations and deaths is still high\n▪Although hospitalization rates are currently low in some age groups, we have seen rates \nincrease in recent weeks and anticipate further increases as we enter respiratory virus season\n▪Infants and older adults have the highest COVID -19-associated hospitalization rates\n▪Children and adults with no underlying medical conditions still experience severe illness due to \nCOVID -19\n▪Post -COVID Conditions are common following SARS -CoV-2 infection, decrease with time since \ninfection, and have decreased since the start of the pandemic\n▪People of racial and ethnic minority groups continue to be disproportionately impacted by \nCOVID -19\n▪High proportions of underlying conditions may put certain groups at increased risk for severe \noutcomes due to COVID -19Summary \nPublic Health Problem \n30\nPublic Health Problem\nWork Group Interpretation\nIs COVID -19 disease among persons ≥ 6 months of public health importance?\noNooProbably no oProbably yes oYesoVaries oDon’t know\nEtR Domain:\nBenefits and Harms \n\n▪Data from COVID -19 vaccine manufacturers \n–Moderna monovalent XBB.1.5 containing vaccine clinical trial data\n–Novavax monovalent XBB.1.5 containing preclinical data\n–Pfizer -BioNTech monovalent XBB.1.5 containing preclinical data\n▪GRADE\n–Benefits and harms of an updated COVID -19 vaccine\n▪Post -authorization safety and effectiveness monitoring\n–Vaccine Safety Datalink and other vaccine safety monitoring systems\n–CDC vaccine effectiveness platforms\n▪Additional considerations\n–Benefit -risk assessment\n–Modeling dataSummary of available data\n33\n▪Moderna\n–Clinical trial data\n•Randomized 101 patients to monovalent XBB.1.5 containing dose or bivalent BA.4/5 + XBB.1.5 containing dose\n•Patients that received the monovalent XBB.1.5 containing dose demonstrated an increase in neutralizing \nantibodies, with similar levels of neutralization across several XBB sub -variants\n•Reported reactogenicity was similar to or lower than that reported from previous doses\n▪Novavax\n–Preclinical data\n•Macaques boosted with XBB.1.5 demonstrated increased neutralizing response across several XBB \npseudoviruses\n▪Pfizer -BioNTech\n–Preclinical data\n•Mice boosted with XBB.1.5 demonstrated increased neutralizing response across several XBB pseudovirusesAvailable data from COVID -19 vaccine manufacturers \n34\n▪GRADE approach was applied to assess the type and quality of evidence for the \nanticipated benefits and harms of an updated COVID -19 vaccine\n▪The PICO question and inclusion/exclusion criteria were intentionally narrow to best \ncapture evidence most applicable to what can be anticipated from this year’s vaccine \ndose in the U.S., including limiting evidence to U.S. studies of an updated vaccine \nformulation (i.e., bivalent mRNA vaccine)\n▪Two separate PICO questions were evaluated based on dosing cut -offs \n▪These narrow criteria reduced the number of studies available in the body of evidence, \nhowever this GRADE assessment builds upon a large body of evidence from the original \nmonovalent vaccinesGRADE \nBLA : Biologics License Application; EUA : Emergency Use Authorization 35\n363636PICO Question –Adolescents and Adults\nPopulation Persons ages 12 years and older\nIntervention Updated mRNA COVID -19 vaccine\nComparison No updated vaccine\nOutcomes Medically -attended COVID -19(ED/UC visits)\nHospitalization due to COVID -19\nDeath due to COVID -19\nPost -COVID Conditions \nSpecified Serious Adverse Events\nReactogenicity\nPICO : Population, intervention, comparison, outcomes  ED: emergency department; UC: urgent care\n373737PICO Question -Infants and Children\nPopulation Persons ages 6 months –11 years\nIntervention Updated COVID -19 mRNA vaccine\nComparison No updated vaccine\nOutcomes Medically -attended COVID -19(ED/UC visits) \nHospitalization due to COVID -19\nDeath due to COVID -19\nMIS-C\nPost -COVID Conditions\nSpecified Serious Adverse Events\nReactogenicity\nPICO : Population, intervention, comparison, outcomes  ED: emergency department; UC: urgent care MIS-C: Multisystem inflammatory syndrome in children \n3838Outcomes, Importance, and Data Sources  \na Three options: Critical; Important but not critical; Not important for decision making\n38Outcome​ ImportanceaData sources\nBenefits\nMedically -attended COVID -\n19(ED/UC visits)Critical Observational studies of vaccine effectiveness \nHospitalization due to COVID -19​ Critical Observational studies of vaccine effectiveness \nDeath due to COVID -19 Important Observational studies of vaccine effectiveness \nMIS-C –pediatrics only Important Observational studies of vaccine effectiveness \nPost -COVID Conditions Important Observational studies of vaccine effectiveness \nHarms\nSpecified serious adverse events​ \n(SAEs)Critical Safety surveillance for specified SAEs \nReactogenicity Important RCTs for monovalent doses\nED: emergency department; UC: urgent care MIS-C: Multisystem inflammatory syndrome in children \nEvidence Retrieval\n▪Observational Studies for Benefits (Vaccine Effectiveness)\n–Published or preprint articles from International Vaccine Access Center (IVAC) \nsystematic reviewa\n–Restricted to PICO defined population, intervention, comparison, and outcome\n▪Safety Surveillance for Serious Adverse Events\n–Data on safety signals identified by vaccine safety surveillance systems\n–Based on input from CDC Immunization Safety Office (ISO)\n▪Randomized Controlled Trials (RCTs) for Reactogenicity\n–Data on reactogenicity identified by relevant phase 1, 2, or 3 RCTs from \nclinicaltrails.gov\n–Unpublished data from vaccine manufacturers\n39a Articles were eligible for inclusion if published or uploaded to a preprint server before 6/29/2023;\nObservational Data (n = 6)\n▪6 records identified (one or more PICO outcomes)\n▪Assessed risk of bias using Newcastle -Ottawa Scale (9 -point scale)\n–For cohort studies: Selection of cohorts, Comparability of cohorts, Assessment of \noutcome\n–For case -control or test -negative design studies: Selection of cases and controls, \nComparability of cases and controls, Ascertainment of exposure\n▪Two reviewers assessed each study for each outcome\n▪Serious limitations identified by score <7\n40\nPooling of Vaccine Effectiveness (VE) Estimates\n▪For each outcome, assessed body of evidence for suitability for pooling\n–Most representative study selected if multiple studies in same population\n▪Meta -analyses conducted \n▪Estimates evaluated for heterogeneity\n▪Resulting pooled estimates summarize real -world data available at time of GRADE \nanalysis\n41\n4242Pooled VE = 53.1% (95% CI: 49.7% to 56.3%)*\n0 10 20 30 40 50 60 70 80 90 100\nVaccine EffectivenessTenforde ,≥7 days post bivalent dose, ≥2 monovalent doses comparator\nTseng, ≥14 days post bivalent dose, ≥2 monovalent doses comparator\nPooled EstimateMedically -Attended COVID -19 (ED/UC Visits), \nAdults and Adolescents (n=2)\n*Pooled RR based on a fixed effects meta -analysis, using adjusted vaccine effectiveness estimates on a log scale. Fixed effects model was used for this \nanalysis due to imprecise estimates of the between -studies variance.\nED: emergency department; UC: urgent care\nGRADE: Medically -Attended COVID -19 (ED/UC Visits), Adults \nand Adolescents (n=2)\n▪Observational Studies (n=2)\n▪Pooled RR 0.47 (95% CI: 0.44 to 0.50)\n▪No serious concerns in certainty assessment. \n▪Evidence type: Low certainty \n43\nCI:Confidence interval; RR:Risk ratio; ED: emergency department; UC: urgent care\n4444Pooled VE = 47.8% (95% CI: 29.6% to 61.4%)*\n*Pooled RR based on a random effects meta -analysis, using adjusted vaccine effectiveness estimates on a log scale .\nNote: 6 studies were identified in the systematic review, however 2 studies had overlapping populations and were excluded fro m the pooled \nanalysis .-40 -20 0 20 40 60 80 100\nVaccine EffectivenessTseng , ≥ 14 post bivalent dose, ≥2 monovalent doses comparator\nLin, ≥ 14 days post bivalent dose, ≥2 monovalent doses comparator\nLink-Gelles, unvaccinated comparator \nSurie, ≥2 monovalent doses comparator\nLink-Gelles, unvaccinated comparator\nSurie, ≥2 monovalent doses comparator \nLink-Gelles, unvaccinated comparator\nSurie, ≥2 monovalent doses comparator\nPooled Estimate7-59 days post \nbivalent dose \n60-119 days post \nbivalent dose \n120-179 days post \nbivalent dose Hospitalization due to COVID -19, Adults and Adolescents (n=4)\nGRADE: Hospitalization due to COVID -19, Adults and Adolescents \n(n=4) \n▪Observational Studies (n=4)\n▪Pooled RR 0.52 (95% CI: 0.39 –0.70)\n▪No serious concerns in certainty assessment.\n▪Evidence type: Low certainty\n45\nCI:Confidence interval; RR:Risk ratio\n4646Death due to COVID -19, Adults and Adolescents (n=2)\n0\n1\n2\n3\n4\n0 10 20 30 40 50 60 70 80 90 100\nVaccine EffectivenessLin,  ≥14 days post bivalent dose, ≥2 monovalent doses comparator\nTseng, ≥14 days post bivalent dose, ≥2 monovalent doses comparator\nPooled Estimate\nPooled VE = 60.5% (95%CI: 40.7% to 73.7%)*\n*Pooled RR based on a fixed effects meta -analysis, using adjusted vaccine effectiveness estimates on a log scale. Fixed effects model was used for this \nanalysis due to imprecise estimates of the between -studies variance.\n47▪Observational Studies (n=2)\n▪Pooled RR 0.39 (95% CI: 0.26 to 0.59)\n▪Serious concern for inconsistency was present. The magnitude of effect and 95% \nconfidence intervals from the two studies in the body evidence varied widely, \npossibly reflecting differences in study methods. \n▪Evidence type: Very lowGRADE: Death due to COVID -19, Adults and Adolescents (n=2) \nCI:Confidence interval; RR:Risk ratio\nPost -COVID -Conditions, Adults and Adolescents\n▪No published or preprint captured in systematic review\n▪Common reasons for exclusion\n–Review article \n–Self-reported vaccination status \n–Combines vaccine platforms\n–Not a VE study\n–Vaccination as a therapeutic (after infection)\n▪Data not captured in the systematic review indicate that COVID -19 vaccine provides \nsome protection against post -COVID conditions\n48\n4949Specified Serious Adverse Events (Myocarditis/Pericarditis)\nIncidence Rate of Verified Myocarditis/Pericarditis in the 0 to 7 Days After mRNA COVID -19 Vaccination among Persons Aged 12 –39 Years by Product, \nAge Group, Sex. \nMonovalent Booster Dose Bivalent Booster Dose \nAge group Cases/Doses AdministeredIncidence Rate/Million Doses \n(95% CI)Cases/Doses Administered Incidence Rate/Million Doses (95% CI)\nPfizer\nMale\n12-17 y - - 0/55649 0.0 (0.0 –53.8)\n12-15 y 5/81613 61.3 (19.9 –143.0) - -\n16-17 y 9/47874 188.0 (86.0 –356.9) - -\n18-29 y 7/166973 41.9 (16.9 –86.4) 1/60338 16.6 (0.4 –92.3)\n30-39 y 3/197554 15.2 (3.1 –44.4) 0/97171 0.0 (0.0 –30.8)\nFemale\n12-17 y - - 0/57776 0.0 (0.0 –51.9)\n12-15 y 0/84114 0.0 (0.0 –35.6) - -\n16-17 y 2/55004 36.4 (4.4 –131.3) - -\n18-29 y 1/240226 4.2 (0.1 –23.2) 0/95162 0.0 (0.0 –31.5)\n30-39 y 1/268412 3.7 (0.1 –20.8) 0/133305 0.0 (0.0 –22.5)\nModerna\nMale\n18-29 y 7/109337 64.0 (25.7 –131.9) 0/22247 0.0 (0.0 –134.7)\n30-39 y 1/149468 6.7 (0.2 –37.3) 1/41820 23.9 (0.6 –133.2)\nFemale\n18-29 y 1/156707 6.4 (0.2 –35.6) 0/35393 0.0 (0.0 –84.6)\n30-39 y 2/191765 10.4 (1.3 –37.7) 0/55816 0.0 (0.0 –53.7)\nSource: Goddard K, et al. Incidence of Myocarditis/Pericarditis Following mRNA COVID -19 Vaccination Among Children and Younger Adults in the United \nStates .Ann Intern Med. 2022;175:1169 -1771. Bivalent booster data through March 11, 2023. Data unpublished.\nSpecified Serious Adverse Events (Anaphylaxis), Adults and \nAdolescents \n▪Among persons 12 and older, based on events occurring in a 0 -1 day risk interval after \nvaccination, the estimated incidence of confirmed anaphylaxis among adolescents and \nadults was:\n–4.8 (95% CI 3.2 -6.9) per million doses of Pfizer -BioNTech original monovalent vaccines\n–5.1 (95% CI: 3.3 -7.4) per million doses of Moderna original monovalent vaccines\n–There were fewer cases of anaphylaxis post dose 2 compared with dose 1\n50\nSource : Klein et al. Surveillance for Adverse Events After COVID -19 mRNA Vaccination. JAMA. 2021;326(14):1390 -1399 \nGRADE: Specified Serious Adverse Events , Adults and \nAdolescents \n▪Observational Studies (n=2)\n▪Two specific, rare SAEs have been associated with vaccination through safety \nsurveillance\n▪No serious concerns in certainty assessment.\n▪Evidence type: Low certainty \n51\nCI:Confidence interval; RR:Risk ratio; SAE: serious adverse events \n52Reactogenicity*, Severe (Grade ≥3), Adults and Adolescents \n(n=4)\nBLA: Biologics License Application\n*Reactogenicity data are from the original monovalent Moderna and Pfizer randomized controlled trials\nGRADE: Reactogenicity, Severe (Grade ≥3), Adults and \nAdolescents\n▪Randomized Controlled Trials (n=4)\n▪Pooled RR 4.83 (95% CI: 4.50 –5.18) \n▪Very serious concern for indirectness, as the body of evidence did not include \nanyone who received an updated dose, were from a prior period of the pandemic, \nand excluded persons with prior COVID -19 infection, pregnant or breastfeeding \nwomen, and persons who were immunocompromised.\n▪Evidence type: Low certainty\n53CI:Confidence interval; RR:Risk ratio\n54Summary of GRADE –Adults and Adolescents\nOutcome​ Importance Design\n(# of studies)​Findings​ Evidence\ntype​\nBenefits\nMedically -attended \nCOVID -19 (ED/UC visit)Critical OBS (2)Updated COVID -19 vaccine is effective in preventing medically \nattended COVID -19 ED/UC visits.Low\nHospitalization due to \nCOVID -19​Critical OBS (4) Updated COVID -19 vaccine prevents hospitalization due to COVID -19 Low\nDeath due to COVID -19 Important OBS (2) Updated COVID -19 vaccine prevents death due to COVID -19 Very low\nPost -COVID Conditions Important OBS (0) - -\nHarms\nSerious adverse events​ Critical OBS (2)In post -authorization safety monitoring, myocarditis and anaphylaxis \nwere rare but more common following vaccinationLow\nReactogenicity Important RCT (4) Severe reactions within 7 days were more common in vaccinated Low\nED: emergency department; UC: urgent care; OBS: observational; RCT: randomized controlled trial\n55Infants and Children Benefits GRADE: \nAdolescent and adult benefits downgraded for indirectness \n▪Systematic review for benefits of vaccination did not capture a sufficient amount of \ndata for evidence synthesis in pediatrics, however data in adults provide indirect \nevidence of benefits\nAdolescents and Adults Pediatrics (with indirectness \ndowngrade)\nOutcome​ Design\n(# of studies)​Pooled VE  (95% CI) Evidence type​ Evidence type\nMedically -attended COVID -19 \n(ED/UC visit)OBS (2) 53.1 (49.7 -56.3) Low Very low\nHospitalization due to COVID -\n19​OBS (4) 47.8 (29.6 -61.4) Low Very low\nDeath due to COVID -19 OBS (2) 60.5 (40.7 -73.7) Very low Very low\nED: emergency department; UC: urgent care; OBS: observational \n56Specified Serious Adverse Events (Myocarditis/Pericarditis), \nInfants and Children\nSource: Goddard et al. Incidence of Myocarditis/Pericarditis Following mRNA COVID -19 Vaccination Among Children and Younger Adults in the Unite d \nStates. Annals of Internal Medicine. https://www.acpjournals.org/doi/10.7326/M22 -2274▪A single observational study from the Vaccine Safety Datalink (VSD) evaluated chart -\nreviewed cases of myocarditis occurring among children aged 5 -11 years following a \nmonovalent booster based on events occurring in a 7 -day risk interval after vaccination vs. \na comparison interval in vaccinated individuals.  \nTable. Incidence Rate of Verified Myocarditis/Pericarditis in the 0 to 7 \nDays After mRNA COVID -19 Vaccination among Persons Aged 5 -11 Years \nby Age Group and Sex. \nAge groupCases/Monovalent \nBooster Doses \nAdministeredIncidence Rate/Million Doses (95% \nCI)\nPfizer\nMale\n5-11 y 0/50415 0.0 (0.0 -59.4)\nFemale\n5-11 y 0/49261 0.0 (0.0 -60.8)\nSpecified Serious Adverse Events (Anaphylaxis), Infants and \nChildren\n▪Risk of anaphylaxis in children can be indirectly inferred from the known risk in persons \nages 12 and older\n–4.8 (95% CI 3.2 -6.9) per million doses of Pfizer -BioNTech original monovalent\n–5.1 (95% CI: 3.3 -7.4) per million doses of original Moderna monovalent \n–There were fewer cases of anaphylaxis post dose 2 compared with dose 1\nSource: Klein et al. Surveillance for Adverse Events After COVID -19 mRNA Vaccination. JAMA. 2021;326(14):1390 -1399 57\nGRADE: Specified Serious Adverse Events, Infants and Children\n▪Observational Studies (n=2)\n▪Two specific, rare SAEs have been associated with vaccination through safety \nsurveillance\n▪Serious concern for indirectness, as the body of evidence for myocarditis was only \namong children aged 5 -11 receiving a monovalent booster and the body of \nevidence for anaphylaxis was among adults and adolescents aged 12 years and \nolder receiving a primary series\n▪Evidence type: Very low certainty\n58CI:Confidence interval; RR:Risk ratio; SAEs: serious adverse events \n5959Reactogenicity*, Severe (Grade ≥3) (n=2), Infants and \nChildren\n59\n *Reactogenicity data are from the original monovalent Moderna and Pfizer randomized controlled trials. \nGRADE: Reactogenicity, Severe (Grade ≥3) (n=2)\n▪RCTs (n=2)\n▪Pooled RR 4.69 (95% CI: 3.43 –6.41) \n▪Very serious concern for indirectness was present. The available body of evidence \ndid not include anyone who received an updated dose and excluded children were \nimmunocompromised. While children with a history of COVID -19 infection were \nincluded in the safety sets, the RCTs were conducted at a time of low \nseroprevalence. \n▪Evidence type: Low certainty\n60CI:Confidence interval; RR:Risk ratio; RCTs: randomized controlled trials\n6161Summary of GRADE –Infants and Children\n61Outcome​ Importance Design\n(# of studies)​Findings​ Evidence\ntype​\nBenefits\nMedically -attended \nCOVID -19 (ED/UC visit)Critical OBS (2)Updated COVID -19 vaccine is effective in preventing medically \nattended COVID -19 ED/UC visits, although the body of evidence is \nlimited to indirect data from adolescents and adultsVery low\nHospitalization due to \nCOVID -19​Critical OBS (4)Updated COVID -19 vaccine prevents hospitalization due to COVID -19, \nalthough the body of evidence is limited to indirect data from \nadolescents and adultsVery low\nDeath due to COVID -19 Important OBS (2)Updated COVID -19 vaccine prevents death due to COVID -19, although \nthe body of evidence is limited to indirect data from adolescents and \nadultsVery low\nPost -COVID Conditions Important OBS (0) - -\nMIS-C Important OBS (0) - -\nHarms\nSerious adverse events​ Critical OBS (2)In post -authorization safety monitoring, two specific adverse events \nhave been associated with vaccinationVery Low\nReactogenicity Important RCT (2) Severe reactions within 7 days were more common in vaccinated Low\nED: emergency department; UC: urgent care; OBS: observational; RCT: randomized controlled trial\n62▪Due to lower uptake of Novavax COVID -19 vaccine, no post -authorization vaccine \neffectiveness estimates from prior COVID -19 vaccine formulation are available\n▪Post -authorization safety data are also limited by the low number of doses \nadministered1\n–Available data from the Vaccine Adverse Event Reporting System (VAERS) are \nconsistent with those from preauthorization clinical trials\n–Most VAERS reports were classified as nonserious\n•The most commonly reported AEs included dizziness, fatigue, and headache\n–No new safety concerns were identifiedNovavax vaccine effectiveness and safety\n1. https://www.cdc.gov/mmwr/volumes/72/wr/mm7231a4.htm\n6363103\n16\n19\n75424\n56\n51\n308476\n76\n95\n414\n0 50 100 150 200 250 300 350 400 450 5006 months –4 years\n18 –49 years5 –11 years\n12 –17 yearsEstimated COVID -19 hospitalizations prevented over 6 months for \nevery million mRNA COVID -19 doses , among those age <50 years, by \nage group\nBased on hospitalization rates from Spring 2023 (low) , December \n2022 (high winter), Summer 2022 (high past year)\n64Calculating Risk: Myocarditis and COVID -19 vaccines\n1 https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2023 -02/slides -02-24/COVID -02-Shimabukuro -508.pdf\n2https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2022 -02-04/11 -COVID -Moulia -508.pdf\n3https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2022 -02-04/04 -COVID -Kracalic -508.pdf\n4https://www.cdc.gov/mmwr/volumes/71/wr/mm7114e1.htm?s_cid=mm7114e1_w▪Limited data to inform myocarditis risk after bivalent COVID -19 vaccine booster dose \n–Myocarditis rates following booster doses in adolescent and young adult males are lower than rates \nfollowing primary series , but estimates are limited by fewer numbers of doses for both the bivalent \nboosters and the previous monovalent boosters administered in VSD1\n▪Myocarditis risk lower with longer time between doses \n–Rates of myocarditis lower with extended interval between dose 1 and dose 2 for primary series2\n–Longer interval between updated doses may also impact myocarditis rates\n▪Most individuals with myocarditis/pericarditis have fully recovered at follow -up3\n▪The risk of adverse cardiac outcomes were 1.8 –5.6 times higher after SARS -CoV-2 infection than after \nmRNA COVID -19 vaccination among males ages 12 -17 years4\n656519–95hospitalizations prevented\n5 –19 ICU admissions prevented\n0 –1death preventedEstimated COVID -19 hospitalizations prevented vs. potential \nmyocarditis cases for every million mRNA COVID -19 vaccine doses: 12 \n–17-year -olds1\nPer million doses in 12 –17-year -olds over 6 months2\n0 myocarditis3cases in 55,649 males with a bivalent dose\n0 myocarditis3cases in 57,776 females with a bivalent dose\n1 Results were adjusted to account for potential incidental findings of SARS -CoV-2 infection by multiplying the estimated hospital izations, ICU admissions, and deaths prevented by the estimated \npercent of COVID -NET hospitalizations that are likely due to COVID -19 among 12 –17-year -olds during on Omicron BA.5 predominant period (55%)\n2 Ranges presented for benefits are based on the high and low incidence scenarios presented on slides 7 and 8\n3Based on preliminary Pfizer -BioNTech bivalent booster safety data from VSD (incident rate/million doses): 0 (95% CI: 0 -54) in m ales and 0 (95% CI: 0 -52) in females  \n6666Universal vaccine recommendations projected to prevent about 400,000 \nhospitalizations and 40,000 deaths over the next 2 years compared with no \nrecommendation, regardless of level of immune escape\nhttps://covid19scenariomodelinghub.org/\n6767Compared with only vaccinating those 65+ years, universal vaccine recommendations \nprojected to prevent about 200,000 more hospitalizations and 15,000 more deaths \nover the next 2 years\nhttps://covid19scenariomodelinghub.org/\nDomain Equity Question:\nAre the desirable and undesirable anticipated effects \ndemonstrated across all populations equally?\n\n▪There is no evidence to suggest that COVID -19 vaccine effectiveness varies substantially \nby race/ethnicity1,2\n–Differences in vaccine hesitancy/uptake, crowding, access to care, and prior infection \ncould impact vaccine effectiveness and these factors may also differ by race/ethnicity \n▪There is no evidence to suggest that COVID -19 vaccine safety profiles vary by \nrace/ethnicity, however risk has been shown to differ by age and sex\n–Risk for myocarditis is highest in adolescent and young adult males\n▪Benefits and harms for the U.S. population are best assessed when clinical trial and \nstudy populations are optimally representative of the U.S. population Are the desirable and undesirable anticipated effects \ndemonstrated across all populations equally?\n1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9619452/\n2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9763212/ 69\n▪Monovalent XBB containing COVID -19 vaccines increase the immune response against the currently \ncirculating variants \n▪Last year’s updated vaccine was effective at preventing medically attended COVID -19, hospitalization \ndue to COVID -19, and death due to COVID -19\n▪Accumulating evidence that COVID -19 vaccination reduces Post -COVID Conditions among both children \nand adults\n▪COVID -19 vaccines have a high degree of safety\n–Rare events of myocarditis and anaphylaxis have been seen in post -authorization studies \n–Unlikely that updating the formulation would increase adverse event rates\n▪Benefits are anticipated in all age groups; benefits of COVID -19 vaccines vary by ageand incidence of \nCOVID -19 hospitalizations\n▪Benefits outweigh risks in age groups for which risk of myocarditis is highest\n▪Modeling projects more hospitalizations and deaths averted when updated doses are universally \nrecommended compared to no recommendation or recommended only for persons ≥65 yearsSummary\nBenefits and Harms \n70\nBenefits and Harms \nHow substantial are the desirable anticipated effects?\n•How substantial are the anticipated effects for each main outcome for which \nthere is a desirable effect?\noMinimal oSmall oModerate oLarge oVaries oDon’t know\nMinority opinion Majority opinion\nBenefits and Harms \nHow substantial are the undesirable anticipated effects?\n•How substantial are the anticipated effects for each main outcome for which \nthere is an undesirable effect?\noMinimal oSmall oModerate oLarge oVaries oDon’t know\nBenefits and Harms \nDo the desirable effects outweigh the undesirable effects?\n•What is the balance between the desirable effects relative to the \nundesirable effects?\noFavors intervention (2023 –2024 COVID -19 vaccine)\noFavors comparison (no vaccine)\noFavors both\noFavors neither\noUnclear\nEtRDomain:\nValues \n\n75Americans’ assessment of COVID -19 in the U.S., February \n2023\nA nationally representative survey of U.S. adults conducted February 21 -28 by web using the Gallup Panel\nGALLUP . At Year Three, Americans Split on Whether Pandemic Is Over. https://news.gallup.com/poll/471734/year -three -americans -split -whether -pandemic.aspx Accessed August \n29, 202362%\n30%\n8%\n0%10%20%30%40%50%60%70%80%90%100%\n4/6/2020\n5/6/2020\n6/6/2020\n7/6/2020\n8/6/2020\n9/6/2020\n10/6/2020\n11/6/2020\n12/6/2020\n1/6/2021\n2/6/2021\n3/6/2021\n4/6/2021\n5/6/2021\n6/6/2021\n7/6/2021\n8/6/2021\n9/6/2021\n10/6/2021\n11/6/2021\n12/6/2021\n1/6/2022\n2/6/2022\n3/6/2022\n4/6/2022\n5/6/2022\n6/6/2022\n7/6/2022\n8/6/2022\n9/6/2022\n10/6/2022\n11/6/2022\n12/6/2022\n1/6/2023\n2/6/2023What’s your impression of the coronavirus situation in the U.S. today?\n% Getting better % Staying about the same % Getting worse\n7630% of U.S. adults report they are very or moderately \nconcerned about getting COVID -19, August 2023 \nA nationally representative sample of U.S. adults aged 18 years and older\nIPSOS KnowledgePanel and NORC AmeriSpeak Omnibus Surveys, results from August 2023 (N=4,299), unpublished data 10.0 20.0 35.2 34.8\n0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%Overall (N=4,289)\nWeighted %Very concerned Moderately A little Not at all\n77Concern about serious COVID -19 illness in family, March 2023 \nMonmouth University. Life Mostly Back to Pre -Covid Normal. Life Mostly Back to Pre -Covid Normal | Monmouth University Polling Institute | Monmouth University Accessed \nAugust 29, 2023\n\nDomain Equity Question:\nIs there important variability in how patients or \npopulations value the outcome?\n\n79Concern about getting COVID -19 by race and ethnicity, August \n2023 \nA nationally representative sample of U.S. adults aged 18 years and older\nIPSOS KnowledgePanel and NORC AmeriSpeak Omnibus Surveys, results from August 2023 (N=4,299), unpublished data 8.812.718.67.8\n27.422.222.117.9\n36.832.632.536.2\n27.032.526.838.1\n0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%Other, non-Hispanic (N=346)Hispanic (N=629)Black, non-Hispanic (N=479)White, non-Hispanic (N=2,835)\nWeighted %Very concerned Moderately A little Not at all\n80Concern about getting COVID -19 by urbanicity, U.S., August \n2023 \nA nationally representative sample of U.S. adults aged 18 years and older\nIPSOS KnowledgePanel and NORC AmeriSpeak Omnibus Surveys, results from August 2023 (N=4,299), unpublished data 10.88.412.2\n17.020.321.2\n35.234.536.2\n37.036.930.4\n0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%Rural (N=765)Suburban (N=2,078)Urban (N=1,446)\nWeighted %Very concerned Moderately A little Not at all\n81Concern about getting COVID -19 by income, August 2023\nA nationally representative sample of U.S. adults aged 18 years and older\nIPSOS KnowledgePanel and NORC AmeriSpeak Omnibus Surveys, results from August 2023 (N=4,299), unpublished data 7.59.413.314.3\n19.923.017.619.7\n36.832.734.933.6\n35.834.934.232.4\n0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%$75,000+ (N=2,076)$50,000-$74,999 (N=789)$25,000-$49,999 (N=801)$24,999 or less (N=623)\nWeighted %Very concerned Moderately A little Not at all\n▪As of February 2023, the majority of Americans felt COVID -19 was getting better\n▪30% of U.S. adults report they are very or moderately concerned about getting COVID -\n19 \n▪Half of U.S. adults continue to have concern about a family member becoming seriously \nill from COVID -19 \n▪Racial and ethnic minority groups, those living in urban areas, and those with lower \nincomes are more concerned about getting COVID -19Summary\nValues\nValues\nCriteria 1:\nDoes the target population feel that that the desirable effects are large relative \nto undesirable effects?\n•How does the target population view the balance of desirable versus undesirable \neffects?\n•Would patients/caregivers feel that the benefits outweigh the harms and burden?\n•Does the population appreciate and value the 2023 –2024 COVID -19 vaccine?\noMinimal oSmall oModerate oLarge oVaries oDon’t know\nMinority opinion Majority opinion\nValues\nCriteria 2:\nIs there important uncertainty about, or variability in, how much people value \nthe main outcomes?\n•How much do individuals value each outcome in relation to the other outcomes?\n•Is there evidence to support those value judgements?\n•Is there evidence that the variability is large enough to lead to different decisions?\noImportant uncertainty or variability\noProbably important uncertainty or variability\noProbably not important uncertainty or variability\noNo important uncertainty or variability\noNo known undesirable outcomesMinority opinionMajority opinion\nEtR Domain:\nAcceptability\n\n86Intent to get new, updated COVID -19 vaccine, August 2023  \nA nationally representative sample of U.S. adults aged 18 years and older\nIPSOS KnowledgePanel and NORC AmeriSpeak Omnibus Surveys, results from August 2023 (N=4,299), unpublished data \n24.9 17.6 18.2 13.6 25.7\n0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%Overall (N=4,283)\nWeighted %Definitely will get vaccine Probably will Unsure Probably will not Definitely will not\n8787Bivalent COVID -19 vaccine receipt and intent among adults 18 \nyears and older, June 2023 \nA nationally representative sample of U.S. adults aged 18 years and older \nIPSOS KnowledgePanel and NORC AmeriSpeak Omnibus Surveys, results from June 2023 (N=4,214), unpublished data \n44.7 3.4\n10.523.8\n8828.1\n0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%Among unvaccinated (N=783)Among 1+ vaccinated (N=3,248)Received bivalent COVID-19 vaccine Definitely will get vaccine\nProbabaly will get vaccine or unsure Probably/definitely will not get vaccine\n8888Top concerns or issues regarding bivalent COVID -19 vaccine, \nJune 2023\nA nationally representative sample of U.S. adults aged 18 years and older \nIPSOS KnowledgePanel and NORC AmeriSpeak Omnibus Surveys, results from June 2023 (N=4,214), unpublished data Received 1+ doses of COVID -19 vaccine \nbut not the bivalent vaccineUnvaccinated with any COVID -19 \nvaccine\nDefinitely will •Too busy or kept forgetting (36.3%) Omitted (N<30)\nProbably will or unsure •Had enough vaccines (27%)\n•Too busy or kept forgetting (22.2%)\n•No provider recommendation (19.8%)\n•Unknown serious side effects (12.8%)•Unknown serious side effects (37.1%)\nProbably or definitely will NOT •Unknown serious side effects (43.1%)\n•Had enough vaccines (42.4%)\n•Not enough studies (33.8%)\n•Do not trust gov’t/pharma (30%)\n•Effectiveness (29.8%)\n•Heart -related issues (28.6%)•Unknown serious side effects (56.5%)\n•Do not trust gov’t/pharma (50.5%)\n•Not enough studies (47.1%)\n•Heart -related issues (39.6%)\n•Effectiveness (36.1%)\n8989Confidence in vaccine safety is higher for influenza and other \nroutine adult vaccines than for COVID -19 vaccine, June 2023 \nAnalysis limited to those who responded to all three survey questions (N=4,164). Omitted category of respondents who answered “not sure” is <1%.\nA nationally representative sample of U.S. adults aged 18 years and older \nIPSOS KnowledgePanel and NORC AmeriSpeak Omnibus Surveys, results from June 2023 (N=4,214), unpublished data \n30.834.323.8\n34.829.525.5\n27.326.429.9\n7.29.820.8\n0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%Routine Adult VaccinesFlu VaccineCOVID-19 VaccineVaccine is completely safe Very safe Somewhat safe Not at all safe\n9090Vaccine recommendation by healthcare provider \n(among those eligible to receive the vaccine), June 2023\nA nationally representative sample of U.S. adults aged 18 years and older \nIPSOS KnowledgePanel and NORC AmeriSpeak Omnibus Surveys, results from June 2023 (N=4,214), unpublished data 72.2\n63.3 62.2\n57.3 56.2\n01020304050607080\nFlu (N=4,169) Shingles (N=2,144) Pneumonia (N=1,851) Tetanus (N=4,158) COVID-19 (N=4,171)Percent reporting HCP recommendation\nAxis Title\n9191Vaccine receipt by healthcare provider recommendation \n(among those eligible to receive the vaccine), June 2023\nA nationally representative sample of U.S. adults aged 18 years and older \nIPSOS KnowledgePanel and NORC AmeriSpeak Omnibus Surveys, results from June 2023 (N=4,214), unpublished data \n9.453.211.951.763.4\n70.794.381.389.189.2\n0.0 10.0 20.0 30.0 40.0 50.0 60.0 70.0 80.0 90.0 100.0ShinglesTetanusPneumoniaFluCOVID-19Provider recommendation No provider recommendation\n(N=2,419)\n(N=1,752)\n(N=3,083)\n(N=1,086)\n(N=2,489)\n(N=1,669)\n(N=1,393)\n(N=751)(N=658)(N=1,193)\n▪Data from the Fall 2022 DocStyles survey were analyzed to examine the prevalence of COVID -19 \nvaccination attitudes and practices among health care providers (HCPs) caring for women of \nreproductive age, and to assess whether providers recommended and offered or administered the \nCOVID -19 vaccines to their pregnant patients \n▪Overall, 82.9% of providers reported recommending COVID -19 vaccination to women of reproductive \nage, and 54.7% offered or administered the vaccine in their practice\n▪Among HCPs who cared for pregnant patients, obstetrician -gynecologists were more likely to \nrecommend COVID -19 vaccination to pregnant patients ( 94.2% ) than were family practitioners/internists \n(82.1% ) \n▪HCPs were more likely to offer or administer COVID -19 vaccination onsite to pregnant patients if they \nalso offered or administered influenza and Tdap vaccines COVID -19 vaccine recommendation and administration by \nU.S. health care providers among women of reproductive age \nFall 2022 DocStyles, unpublished data (data will be published in MMWR on September 28, 2023) 92\nDomain Equity Question:\nIs the intervention equally acceptable across all \npopulations?\n\n9494COVID -19 vaccine safety confidence by race and ethnicity, \nAugust 2023\nA nationally representative sample of U.S. adults aged 18 years and older\nIPSOS KnowledgePanel and NORC AmeriSpeak Omnibus Surveys, results from August 2023 (N=4,299), unpublished data \n20.622.318.923.2\n32.226.324.624.9\n32.730.536.328.6\n14.520.920.223.3\n0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%Other, non-Hispanic (N=347)Hispanic (N=626)Black, non-Hispanic (N=476)White, non-Hispanic (N=2,830)\nWeighted %Vaccine is completely safe Very safe Somewhat safe Not at all safe\n9595COVID -19 vaccine safety confidence by income, August 2023 \nA nationally representative sample of U.S. adults aged 18 years and older\nIPSOS KnowledgePanel and NORC AmeriSpeak Omnibus Surveys, results from August 2023 (N=4,299), unpublished data \n26.921.218.114.7\n29.726.020.120.5\n25.530.637.135.7\n17.822.224.729.1\n0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%$75,000+ (N=2,075)$50,000-$74,999 (N=788)$25,000-$49,999 (N=797)$24,999 or less (N=619)\nWeighted %Vaccine is completely safe Very safe Somewhat safe Not at all safe\n9696COVID -19 vaccine safety confidence by urbanicity, August \n2023 \nA nationally representative sample of U.S. adults aged 18 years and older\nIPSOS KnowledgePanel and NORC AmeriSpeak Omnibus Surveys, results from August 2023 (N=4,299), unpublished data \n16.423.124.4\n20.227.027.0\n33.429.429.6\n30.020.519.0\n0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%Rural (N=762)Suburban (N=2,075)Urban (N=1,442)\nWeighted %Vaccine is completely safe Very safe Somewhat safe Not at all safe\n97Intent to get new, updated COVID -19 vaccine by age, August \n2023\nA nationally representative sample of U.S. adults aged 18 years and older\nIPSOS KnowledgePanel and NORC AmeriSpeak Omnibus Surveys, results from August 2023 (N=4,299), unpublished data \n43.12815.8\n18.619.416.3\n13.116.221.2\n9.111.816.3\n1624.530.3\n0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%Age 65+ (N=1,091)Age 50-64 (N=1,109)Age 18-49 (N=2,083)\nWeighted %Definitely will get vaccine Probably will Unsure Probably will not Definitely will not\n9898Percent of people receiving COVID -19 vaccine by age\n*Data cutoff on May 10, 2023 is due to the end of the Public Health Emergency (PHE) on May 11, 2023\nData source: VTrcks , IIS, Federal Pharmacy Program, Federal Entities Program, U.S. Census Bureau 10 -year July 2019 National Population Estimates\nhttps://covid.cdc.gov/covid -data -tracker/#vaccination -demographics -trends . Accessed 9/5/2023\nDecember 14, 2020 –May 10, 2023*\n99Intent to get new, updated COVID -19 vaccine by race and \nethnicity, August 2023\nA nationally representative sample of U.S. adults aged 18 years and older\nIPSOS KnowledgePanel and NORC AmeriSpeak Omnibus Surveys, results from August 2023 (N=4,299), unpublished data \n21.822.227.925.5\n19.521.71716.3\n22.722.119.416.2\n17.111.61413.6\n18.922.421.728.5\n0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%Other, non-Hispanic (N=347)Hispanic (N=626)Black, non-Hispanic (N=478)White, non-Hispanic (N=2,832)\nWeighted %Definitely will get vaccine Probably will Unsure Probably will not Definitely will not\n10\n0100Estimated percent of people ≥ 18 years reporting COVID -19 \nvaccination by race/ethnicity\nSource: National Immunization Survey Adult COVID Module. https://covid.cdc.gov/covid -data -tracker/#vaccination -demographics -trends. Accessed 9/5/2023National Immunization Survey Adult COVID Module, April 22, 2021 –March 25, 2023\n\n10\n1101COVID -19 v accine receipt by healthcare provider \nrecommendation by race and ethnicity, June 2023 \nA nationally representative sample of U.S. adults aged 18 years and older \nIPSOS KnowledgePanel and NORC AmeriSpeak Omnibus Surveys, results from June 2023 (N=4,214), unpublished data \n66.164.165.262.4\n94.58983.689.4\n0 10 20 30 40 50 60 70 80 90 100Other, non-HispanicHispanicBlack, non-HispanicWhite, non-HispanicProvider recommendation No provider recommendation\n(N=1,102)(N=1,690)\n(N=253)\n(N=220)\n(N=306)\n(N=298)\n(N=170)\n(N=132)\n10\n2102Percent of pregnant people ages 18 -49 years who are up to date* with \nCOVID -19 vaccines overall and by race and ethnicity –Vaccine Safety \nDatalink, September 1, 2022 –July 29, 2023\n*Up to date is defined as the percent of pregnant people who received an updated bivalent dose before or during pregnancy, wit h the denominator including those pregnant at \nleast 1 day during the specified month ending date, and the numerator including those who received an updated bivalent dose. CDC recommended bivalent boosters to persons \nage ≥12 years starting September 1, 2022. Data on bivalent boosters among pregnant persons was available starting September 4 , 2022, and includes doses received starting \nSeptember 1, 2022\nCDC. COVID -19 vaccination among pregnant people aged 18 -49 years overall, by race and ethnicity, and date reported to CDC –Vacc ine Safety Datalink,* United States. \nhttps://covid.cdc.gov/covid -data -tracker/#vaccinations -pregnant -women Accessed August 9, 2023\n\n▪Vaccine receipt varies by age and race/ethnicity\n▪Fall vaccination intent increases with increasing age; those ages 65+ have the highest \npercentage reporting they “definitely” or “probably” will get the vaccine compared to \nother age groups \n▪Confidence in COVID -19 vaccine safety differs across the population\n▪Compared to other vaccines, COVID -19 vaccines were recommended the least by \nhealth care providers \n▪Those who received a provider recommendation overall and by race and ethnicity were \nmore likely to receive the recommended vaccine\n▪Encouraging health care providers to recommend, offer, and administer COVID -19 \nvaccines, could help reinforce vaccine confidence and increase coverage1Summary\nAcceptability \n103\n1. Fall 2022 DocStyles, unpublished data\nAcceptability\nIs the 2023 –2024 COVID -19 vaccine acceptable to key stakeholders?\n•Are there key stakeholders that would not accept the distribution of benefits \nand harms?\n•Are there key stakeholders that would not accept the undesirable effects in \nthe short term for the desirable effects (benefits) in the future?\noNooProbably no oProbably yes oYesoVaries oDon’t know\nMinority opinion Majority opinion\nEtR Domain:\nFeasibility \n\n▪Vaccines with a monovalent XBB.1.5 composition will be the first COVID -19 vaccines to \nbe available directly from the manufacturers as part of the commercial market, rather \nthan through the United States Government (USG)\n▪The public will continue to be directed to Vaccines.gov to find providers offering COVID -\n19 vaccine\n▪While providers will no longer be required to report inventory to Vaccines.gov after \nvaccines transition to being available on the commercial market, they will continue to \nbe encouraged to report voluntarily\n–Providers are also strongly encouraged to report the minimum age (in months and \nyears) for whom a location can administer vaccine\n▪CDC will continue its efforts to make sure that all people have access to COVID -19 \nmedical countermeasures and know where to find product now and in the future Fall COVID -19 vaccine transition \nCDC. HHS Commercialization Transition Guide: Sunsetting the US Government COVID -19 Vaccine Distribution Program. https://www.cdc.gov/vaccines/covid -19/downloads/HHS -\nCommercialization -Transition -Guide -508.pdf Accessed August 4, 2023 106\n▪Inclusion of COVID -19 vaccines in Vaccines for Children (VFC) will likely result in more pediatricians \nstocking the vaccine \n▪There will be single dose vial presentations and smaller minimum order quantities \n–Directly addresses concerns from health care providers (HCPs), likely to reduce wastage, eases logistics \nand helps with storage capacity limitations\n•Moderna, 12+ years: single dose vial (10 -pack) and manufacturer -prefilled syringes (10 -pack)\n•Moderna, 6 months –11 years: single dose vial (10 -pack)\n•Novavax, 12+ years: 5 -dose multi -dose vial (2 vials per carton)\n•Pfizer, 12+ years: single dose vial (10 -pack), limited quantity of manufacturer -prefilled syringes (10 -\npack)\n•Pfizer, 5 –11 years: single dose vial (10 -pack)\n•Pfizer, 6 months –4 years: 3 -dose multi -dose vial (10 -pack)\n▪Preparation is the same or simpler than it was before\n–Moderna preparation is the same (no dilution)\n–Novavax preparation is the same (no dilution)\n–Pfizer preparation is simplified (currently 2 presentations require dilution; for 2023 –2024 COVID -19 \nvaccine, ONLY little peds formulation require dilution) Feasibility of vaccine implementation\nImmunization Services Division, internal planning documents \n▪Storage and handling will be the SAME as it is now\n–Moderna: Frozen until expiration; 30 days at refrigerator storage\n–Novavax: Stable at 2 -8°C (refrigerator storage); 9 -month shelf life; use within 12 hours \nof first puncture\n–Pfizer: Ultra -cold storage until expiration; 10 weeks at refrigerator storage\n•Ultra -cold storage continues to be a challenge; most provider offices do not have a \nunit \n▪Dose volume for Pfizer is simplified (all doses are 0.3mL) \n▪Moderna now only has two presentations, reducing the chance for errorsFeasibility of vaccine implementation, cont’d\nImmunization Services Division, internal planning documents \n▪There are now THREE seasonal vaccines and preventative products1for respiratory \ndiseases to manage\n–More seasonal vaccines to manage \n–Limited storage space and more vaccines\n–More opportunities for vaccine administration errors \n▪Providers have to adapt to new cap/label colors\n–Moderna: 6 months –11 years is blue cap/ green label; 12+ years is blue cap/ blue\nlabel\n–Novavax: 12+ is blue\n–Pfizer: 6 months –4 years is yellow ; 5 –11 years is blue ; 12+ years is gray\n▪Moderna, Novavax and Pfizer all have products with blue caps, introducing opportunity \nfor errorBarriers to implementation\n1 COVID -19 vaccine, Influenza vaccine,  RSV vaccine, and nirsevimab , a long -acting monoclonal antibody for RSV prevention in infants\nImmunization Services Division, internal planning documents \nDomain Equity Question:\nIs the intervention equally feasible to implement \nacross all populations?\n\n11\n1111There are disparities in uninsured status that could impact \nwho gets a COVID -19 vaccine\n0%5%10%15%20%25%\nWhite Black American Indian\nand Alaska NativeAsian Native Hawaiian\nand Other Pacific\nIslanderHispanic or LatinoPercent of US adults without health insurance\nU.S. Census Bureau, 2021 American Community Survey 1 -year estimates: https://data.census.gov/table?q=race&t=Health+Insurance&tid=ACSST1Y2021.S2701\n▪CDC will provide access to COVID -19 vaccines for uninsured individuals once COVID -19 \nvaccines become commercially available1\n▪Uninsured children will be able to receive COVID -19 vaccines through the existing \nVaccines for Children (VFC) program1\n–The VFC program offers vaccines at no low or no cost to eligible children through a national network of \nparticipating health care providers2\n▪Adults who are uninsured or underinsured will be able to receive no -cost COVID -19 \nvaccines through the temporary Bridge Access Program for COVID -19 Vaccines. This \nprogram consists of two components:\n–Public health infrastructure: through state immunization programs, State and local health departments and HRSA -\nsupported health centers will provide no -cost COVID -19 vaccines to adults who are uninsured or underinsured\n–Participating retail pharmacies: CVS, Walgreens, and eTrueNorth will continue to provide no -cost COVID -19 \nvaccines to adults who are uninsured or underinsured3CDC vaccine programs for people who are uninsured\n1.CDC. HHS Commercialization Transition Guide: Sunsetting the US Government COVID -19 Vaccine Distribution Program. https://www.cdc.gov/vaccines/covid -\n19/downloads/HHS -Commercialization -Transition -Guide -508.pdf Accessed August 4, 2023\n2.CDC. VFC Information for Parents. https://www.cdc.gov/vaccines/programs/vfc/parents/index.html Accessed August 30, 2023\n3.CDC. Bridge Access Program for COVID -19 Vaccines. https://www.cdc.gov/vaccines/programs/bridge/index.html Accessed September 7, 2023 112\n▪CDC's Bridge Access Program for COVID -19 Vaccines and COVID -19 vaccine \nimplementation plans are intentionally designed to overcome barriers to access and \navailability\n–This includes design for maximized proximity to no -cost COVID -19 vaccines among \npopulations of people who are uninsured or underinsured\n▪CDC and HHS continue to invest in health systems and programs that support vaccine \naccess and outreach in underserved communities –such as HRSA -Supported Health \nCenters, Rural Health Clinics, and State and local health departments\n–These networks can be leveraged for access to COVID -19 vaccines as well as other \nneeded medicinesAvailability of vaccines in underserved communities \nASPR Administration for Strategic Preparedness & Response. Commercialization of COVID -19 Medical Countermeasures. https://aspr.hhs.gov/COVID -19/Pages/FAQ -\nCommercialization.aspx Accessed August 25, 2023 113\n▪Implementation of the 2023 –2024 COVID -19 vaccine will likely reduce wastage, ease \nlogistics, help with storage capacity limitations and reduce the chance of errors\n▪Nevertheless, there will be now be three seasonal vaccines for respiratory diseases, in \nwhich there will be more seasonal vaccines to manage, limited storage space due to \nadditional vaccines and more opportunities for vaccine administration errors\n▪Vaccines will continue to be accessible after commercialization, with readily available \nresources for those who are uninsured, underinsured, or who reside in underserved \ncommunitiesSummary\nFeasibility \n114\nFeasibility\nIs the 2023 –2024 COVID -19 vaccine feasible to implement among \npopulations currently recommended for a dose?\n•Is the 2023 –2024 COVID -19 vaccine program sustainable?\n•Are there barriers that are likely to limit the feasibility of implementing the 2023 –\n2024 COVID -19 vaccine or require considerations when implementing it?\n•Is access to the 2023 –2024 COVID -19 vaccine an important concern?\noNooProbably no oProbably yes oYesoVaries oDon’t know\nEtR Domain:\nResource Use \n\n▪COVID -19 vaccination is a cost –effective intervention, particularly in persons ages ≥65 \nyears in which the vaccine is cost saving\n▪Cost -effectiveness estimates in those ages ≥50 years were robust to input changes \nacross plausible ranges\n▪Cost -effectiveness estimates in those 18 -49 years were sensitive to changes in inputs\n–If vaccine effectiveness or hospitalization rates are higher than anticipated, the cost -\neffectiveness estimates would be more favorable\n▪Cost -effectiveness estimates are not yet available for pediatric populationSummary\n117\nDomain Equity Question:\nIs the intervention a reasonable and efficient \nallocation  of resources across all populations?\n\n▪COVID -19 vaccination is most cost -effective in older adults in which disease burden is \nhighest compared to younger adults\n▪COVID -19 vaccination is likely more cost -effective in populations with risk factors, such \nas underlying conditions, which increase their probability of hospitalization due to \nCOVID -19 \n▪Additional work is ongoing to evaluate cost -effectiveness in the pediatric populationsIs the intervention a reasonable and efficient allocation  of \nresources across all populations?\n119\nResource Use\nIs the 2023 –2024 COVID -19 vaccine a reasonable and efficient allocation of \nresources?\n•What is the cost -effectiveness of the 2023 –2024 COVID -19 vaccine?\n•How does the cost -effectiveness of the 2023 –2024 COVID -19 vaccine change in \nresponse to changes in context, assumptions, etc.?\noNooProbably no oProbably yes oYesoVaries oDon’t know\nMinority opinion Majority opinion\nSummary and Work Group Interpretations  \n▪The burden of COVID -19 varies by age and underlying condition status with those ages ≥65 years and \nthose with multiple underlying conditions having the highest risk of severe outcomes due to COVID -19\n▪COVID -19 burden is currently lower than at previous points in the pandemic, however there are still \nthousands of hospitalizations and hundreds of deaths each week\n▪Children and adults ages 5 –49 years had the lowest hospitalization rates overall\n–Severe outcomes occur in this age group, including in people with no underlying medical conditions\n▪Although hospitalization rates are currently low, we have seen rates increase in recent weeks and \nanticipate further increases as we enter respiratory virus season\n▪Majority of U.S. population has some level of immunity due to infection, vaccination, or both\n–Vaccine and infection -induced immunity wane and new variants have emerged, suggesting that\nsusceptibility remains and may increase over time\n▪Racial and ethnic minority groups have been disproportionately affected by COVID -19Summary and Work Group Interpretation: \nPublic Health Burden\n122\n▪Monovalent XBB containing COVID -19 vaccines increase the immune response against the currently \ncirculating variants \n▪Last year’s updated vaccine was effective at preventing medically attended COVID -19, hospitalization \ndue to COVID -19, and death due to COVID -19\n▪COVID -19 vaccines have a high degree of safety\n–Unlikely that updating the formulation would increase adverse event rates\n▪Benefits are anticipated in all age groups; benefits of COVID -19 vaccines vary by age, and incidence of \nCOVID -19 hospitalizations\n▪Benefits outweigh risks in age groups for which there is a risk of myocarditis\n▪Modeling projects more hospitalization and deaths averted when updated doses are universally \nrecommended compared to no recommendation or recommended only for persons ≥65 yearsSummary and Work Group Interpretation:\nBenefits and Risks\n123\n▪Work Group considered non -universal policy options, with considerable discussion around the magnitude of benefits in \nthe young, healthy population\n▪As part of these deliberations, Work Group requested additional data on severe illness due to COVID -19 in those with \nand without underlying conditions\n–No group that clearly had no risk of severe illness\n–The vast majority of the US population has an underlying condition that would qualify under a risk based \nrecommendation\n•Prevalence of overweight and obesity alone is >70% of adults1\n–Risk based recommendation would not allow access to COVID -19 vaccines for all that wanted them \n▪Shared clinical decision making could create barriers to vaccination and may not effectively target those at highest risk\n▪COVID -19 epidemiology remains uncertain and non -universal recommendations would need to be quickly revisited if \nthere was an increase in burden\n▪Still substantial COVID -19 disease burden and simple, stable recommendations may increase vaccine coverage over time\n▪Work Group emphasized that COVID -19 recommendations should be reviewed on an ongoing basis as more is learned \nabout COVID -19 seasonality and disease burden in the futureSummary and Work Group Interpretation:\nConsiderations Regarding a Universal vs. Non -universal Policy\n1National Health Statistics Reports; https://stacks.cdc.gov/view/cdc/106273124\n▪Burden of severe illness due to COVID -19 is lowest among children ages 5 –17 years\n▪Despite lower burden relative to other age groups, hundreds of deaths due to COVID -19 occurred in this \nage group in 2021 and 2022\n–Half of pediatric COVID -19 deaths were in individuals with no underlying conditions\n▪Number of COVID -19 hospitalizations and deaths in this age group are comparable to the burden seen in \nother vaccine preventable diseases for which there are universal recommendations\n▪Potential additional benefits of vaccination , such as prevention of post -COVID conditions and potential \nfor reduced school absenteeism \n▪Risk of myocarditis appears lower than the risk observed following primary series doses\n–Potentially lower due to increased interval between doses\n–Certainty is limited by relatively lower sample size of booster recipients in VSD\n▪Future COVID -19 epidemiology remains uncertain and the low disease burden we are currently seeing \nmay not last\n▪After a robust discussion, Work Group was supportive of a universal recommendation at this timeSummary and Work Group Interpretation: \nCOVID -19 vaccine recommendations for children \n125\n126EtR Domain​​​ ​​Question​ Work Group Judgments\nPublic Health \nProblem​​​Is COVID -19 of public health importance?​​​ Yes\nBenefits and HarmsHow substantial are the desirable anticipated effects? Large\nHow substantial are the undesirable anticipated effects? Small\nDo the desirable effects outweigh the undesirable effects? Favors intervention\nValues​​​Does the target population feel the desirable effects are large \nrelative to the​ undesirable effects?​Moderate \nIs there important variability in how patients value the \noutcomes?Probably important \nuncertainty or variability\nAcceptability​​​Is the 2023 -2024 COVID -19 vaccine acceptable to key \nstakeholders?​​​Yes / Probably yes / Varies\nFeasibility​​​ Is the 2023 -2024 COVID -19 vaccine feasible to implement?​​​ Yes\nResource Use​​​Is the 2023 -2024 COVID -19 vaccine a reasonable and efficient \nallocation of resources?​​​Yes\n127Evidence to Recommendations Framework\nSummary: Work Group Interpretations \nBalance of \nconsequencesUndesirable \nconsequences \nclearly \noutweigh \ndesirable \nconsequences \nin most \nsettingsUndesirable \nconsequences \nprobably \noutweigh \ndesirable \nconsequences \nin most \nsettingsThe balance \nbetween \ndesirable and \nundesirable \nconsequences \nis closely \nbalanced or \nuncertainDesirable \nconsequences \nprobably \noutweigh \nundesirable \nconsequences \nin most \nsettingsDesirable \nconsequences \nclearly \noutweigh \nundesirable \nconsequences \nin most \nsettingsThere is \ninsufficient \nevidence to \ndetermine the \nbalance of \nconsequences\nMinority opinion Majority opinion\n128Evidence to Recommendations Framework\nSummary: Work Group Interpretations \nType of \nrecommendationWe do not recommend \nthe interventionWe recommend the \nintervention for individuals \nbased on shared clinical \ndecision -makingWe recommend the \nintervention \nACIP recommends 2023 –2024 (monovalent, XBB containing) \nCOVID -19 vaccines as authorized under Emergency Use \nAuthorization (EUA) or approved by Biologics License Application \n(BLA) in persons ≥6 months of ageProposed ACIP Voting Language\n129\nClinical Considerations\n130\n▪Everyone ages 5 years and older is recommended to receive 1 dose of a 2023 –2024 \nmRNA COVID -19 vaccine\n▪Children ages 6 months –4 years should complete a multi -dose initial series (2 doses of \nModerna or 3 doses of Pfizer -BioNTech mRNA COVID -19 vaccine) with at least one dose \nof the 2023 –2024 COVID -19 vaccine1\n▪People who are moderately or severely immunocompromised should complete a 3 -\ndose initial series with at least one dose of the 2023 –2024 COVID -19 vaccine and may \nreceive 1 or more additional 2023 –2024 COVID -19 vaccine doses2\n▪Bivalent mRNA COVID -19 vaccines are no longer recommended in the United StatesProposed 2023 –2024 mRNA COVID -19 vaccine \nrecommendations:\n1.Children ages 6 months –4 years that previously received a single dose of Pfizer -BioNTech vaccine should receive 2 doses of Pfi zer-BioNtech vaccine.  \n2.Additional details in the interim clinical considerations 131\nBivalent recommendations Proposed 2023 –2024 \nvaccine recommendationsRationale\nEveryone ages 6 years and \nolder recommended for a \nsingle bivalent doseEveryone ages 5 years and \nolder recommended for a \nsingle 2023 –2024 doseEliminates complex \nrecommendations for 5 -year -\nolds\nTwo Moderna dosages \nauthorized for 6 months –5 \nyears, depending on \nvaccination history and \nimmune statusAll Moderna doses in ages 6 \nmonths –11 years are now 25 \nµcgReduces the number of \nCOVID -19 vaccine products in \nuse\nOptional 2ndbivalent dose for \nthose ages 65 years and olderNo additional dose \nrecommendation at this timeWill monitor epidemiology \nand vaccine effectiveness to \ndetermine if additional doses \nare neededKey changes from bivalent mRNA recommendations\nAcknowledgements\n133▪Monica Godfrey\n▪Danielle Moulia\n▪Hannah Rosenblum\n▪Katherine Fleming -Dutra\n▪Ruth Link -Gelles\n▪Sarah Meyer\n▪Elisha Hall\n▪Joanna Regan \n▪Susan Goldstein\n▪Mary Chamberland\n▪JoEllen Wolicki\n▪Josephine Mak\n▪Morgan Najdowski\n▪Lauren Roper\n▪Karen Broder \n▪Melisa Shah▪Mehreen Meghani\n▪Romeo Galang\n▪Sascha Ellington \n▪Sierra Scarbrough\n▪Amadea Britton\n▪Jefferson Jones\n▪Aron Hall\n▪Barbara Mahon\n▪COVID -NET\n▪COVID -19 Scenario Modeling Hub\n▪University of Michigan COVID -19 Vaccination Modeling \nTeam\n▪Immunization Safety Office\n▪Immunization Services Division\n▪Coronavirus and other Respiratory Viruses Division\n▪National Center for Immunization and Respiratory \nDiseases\nFor more information, contact CDC\n1-800 -CDC -INFO (232 -4636)\nTTY:  1 -888 -232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention.\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nThank you \nAdditional Clinical Considerations \nProposed recommendations for children aged 6 \nmonths –4 years who are notmoderately or \nseverely immunocompromised\n▪All doses should be homologous (i.e., from the same manufacturer) \n▪All Moderna doses in ages 6 months –11 years are now 25 µcg Proposed recommendations for children aged 6 months –4 years \nwithout immunocompromise\nDoses recommended:\n▪Initial series of 2 Moderna vaccine doses OR 3 \nPfizer -BioNTech vaccine doses \n▪At least 1 dose of 2023 –2024 COVID -19 vaccine \nVaccinated\n1 dose any \nPfizer -\nBioNTech2 doses any \nPfizer -\nBioNTech3 or more \ndoses any \nPfizer -\nBioNTech\n2023 –2024 \nModerna2 doses\n2023 –2024 \nPfizer -\nBioNTech3 doses\n0.3 mL/3 µg 0.25 mL/25 µgPreviously received \nCOVID -19 vaccine(s)\nRecommendations \nfor 2023 –2024 \nvaccine, by \nmanufacturerUnvaccinated\nOR\n2023 –2024 \nModerna1 dose\n0.25 mL/25 µg2023 –2024 \nPfizer -\nBioNTech2 doses\n0.3 mL/3 µg2023 –2024 \nPfizer -\nBioNTech1 dose\n0.3 mL/3 µgProposed recommended 2023 –2024 COVID -19 mRNA vaccines for people who are NOT immunocompromised, \naged 6 months –4 years*\n1 dose any \nModerna2 or more \ndoses any \nModerna\n*For information about administration intervals and people who transition from age 4 years to age 5 years during an mRNA vaccination series, see Table 1 in the \nInterim Clinical Considerations for Use of COVID -19 vaccines .COVID -19 vaccination \nstatus as of \nSeptember 2023\nProposed recommendations for people aged 5 \nyears and older who are notmoderately or \nseverely immunocompromised\nProposed recommendations for people aged 5 years and older \nwithout immunocompromise \nDoses recommended:\n•1 dose of 2023 –2024 COVID -19 vaccine , \nregardless of prior vaccination history\n▪New harmonized age cutoff for recommendations for young children for Moderna and \nPfizer -BioNTech COVID -19 vaccines\n▪Resulting in simplified recommendations for 5 -year -olds\n▪All Moderna doses in ages 6 months –11 years are now 25 µcg \n▪2023 –2024 COVID -19 vaccine dose is recommended at least 2 months after receipt of \nthe last COVID -19 vaccine dose\nVaccinated\nPreviously received \nCOVID -19 vaccine(s)\nRecommendations \nfor 2023 –2024 \nvaccine, by \nmanufacturerUnvaccinated\n2023 –2024 \nModerna1 dose\n0.25 mL/25 µg2023 –2024 \nPfizer -\nBioNTech1 dose\n0.3 mL/10 µgProposed r ecommended 2023 –2024 COVID -19 mRNA vaccines for people who are NOT immunocompromised, \naged 5 –11 years*\n1 or more \ndoses any \nmRNA\n*For information about administration intervals and people who transition from age 4 years to age 5 years during an mRNA vaccination series, see Table 1 in the \nInterim Clinical Considerations for Use of COVID -19 vaccines .ORCOVID -19 vaccination \nstatus as of \nSeptember 2023\nPreviously received \nCOVID -19 vaccine(s)\nRecommendations \nfor 2023 –2024 \nvaccine, by \nmanufacturerUnvaccinated\n2023 –2024 \nModerna1 dose\n0.5 mL/50 µg2023 –2024 \nPfizer -\nBioNTech1 dose\n0.3 mL/30 µgProposed r ecommended 2023 –2024 COVID -19 mRNA vaccines for people who are NOT immunocompromised, aged ≥12 years*\n1 or more \ndoses any \nmRNAVaccinated\n1 or more doses Novavax \nor Janssen, including in \ncombination with any \nmRNA vaccine dose(s)\n*For information about administration intervals ,see Table 1 in the Interim Clinical Considerations for Use of COVID -19 vaccines .ORCOVID -19 vaccination \nstatus as of \nSeptember 2023\nProposed recommendations for people who are \nmoderately or severely immunocompromised\nProposed recommendations for people aged ≥6 months who are \nmoderately or severely immunocompromised\nDoses recommended:\n▪Initial COVID -19 vaccine series*\n▪At least 1 2023 –2024 COVID -19 vaccine dose\n▪May receive 1 or more additional 2023 -2024 \nmRNA COVID -19 vaccine doses**\n*Series of 3 homologous mRNA COVID -19 vaccine doses at time of initial vaccination. This could also include \na history of receipt of 1 or more doses of Novavax or Janssen, including in combination with mRNA vaccine \ndose(s). \n**Further additional dose(s) may be administered, informed by the clinical judgement of a healthcare \nprovider and personal preference and circumstances. Further additional doses should be administered at \nleast 2 months after the last 2023 -2024 COVID -19 vaccine dose. \n1 dose any \nPfizer -\nBioNTech2 doses any \nPfizer -\nBioNTech3 or more \ndoses any \nPfizer -\nBioNTech\n2023 –2024 \nModerna3 doses\n2023 –2024 \nPfizer -\nBioNTech3 doses\n0.3 mL/3 µg 0.25 mL/25 µgCOVID -19 vaccination \nstatus as of \nSeptember 2023\nPreviously received \nCOVID -19 vaccine(s)\nRecommendations \nfor 2023 –2024 \nvaccine, by \nmanufacturerUnvaccinated\n2023 –2024 \nModerna2 doses\n0.25 mL/25 µg2023 –2024 \nPfizer -\nBioNTech2 doses\n0.3 mL/3 µg2023 –2024 \nPfizer -\nBioNTech1 dose\n0.3 mL/3 µgProposed r ecommended 2023 –2024 COVID -19 vaccines for people who ARE moderately or severely immunocompromised, \naged 6 months –4 years* \n1 dose any \nModerna\n2023 –2024 \nModerna1 dose\n0.25 mL/25 µgVaccinated\n2 doses any \nModerna3 or more \ndoses any \nModerna\n*For information about administration intervals, people who transition from age 4 years to age 5 years during an mRNA vaccina tion series, and administration \nof additional dose(s), see Table 2 in Interim Clinical Considerations for Use of COVID -19 Vaccines. OR\n2023 –2024 \nModerna3 doses\n0.25 mL/25 µgPreviously received \nCOVID -19 vaccine(s)\nRecommendations \nfor 2023 –2024 \nvaccine, by \nmanufacturerUnvaccinated\n2023 –2024 \nModerna2 doses\n0.25 mL/25 µgProposed r ecommended 2023 –2024 COVID -19 vaccines for people who ARE moderately or severely immunocompromised, \naged 5 –11 years*\n2 doses any \nModerna\n2023 –2024 \nModerna1 dose\n0.25 mL/25 µg2023 –2024 \nPfizer -\nBioNTech2 doses\n0.3 mL/10 µg2023 –2024 \nPfizer -\nBioNTech1 dose\n0.3 mL/10 µg1 dose any \nModerna1 dose any \nPfizer -\nBioNTech2 doses any \nPfizer -\nBioNTech3 or more doses \nany mRNA \nvaccineVaccinated\n*For information about administration intervals, people who transition from age 4 years to age 5 years or age 11 years to age 12years during an mRNA \nvaccination series, and administration of additional dose(s), see Table 2 in Interim Clinical Considerations for Use of COVID -19Vaccines. OR\n2023 –2024 \nPfizer -\nBioNTech3 doses\n0.3 mL/10 µgOR\n2023 –2024 \nPfizer -\nBioNTech1 dose\n0.3 mL/10 µg2023 –2024 \nModerna1 dose\n0.25 mL/25 µgCOVID -19 vaccination \nstatus as of \nSeptember 2023\nPreviously received \nCOVID -19 vaccine(s)\nRecommendations \nfor 2023 –2024 \nvaccine, by \nmanufacturerUnvaccinated\nORProposed r ecommended 2023 –2024 COVID -19 vaccines for people who ARE moderately or severely immunocompromised, \naged ≥12 years*\n2 doses \nany \nModerna\nOR1 dose \nany \nModerna1 dose \nany \nPfizer -\nBioNTech2 doses \nany \nPfizer -\nBioNTech1 or more doses of \nNovavax or Janssen, \nincluding in \ncombination with any \nmRNA vaccine dose(s)Vaccinated\n2023 –2024 \nModerna3 doses\n0.5 mL/50 µg2023 –2024 \nPfizer -\nBioNTech3 doses\n0.3 mL/30 µg2023 –2024 \nModerna2 doses\n0.5 mL/50 µg2023 –2024 \nModerna1 dose\n0.5 mL/50 µg2023 –2024 \nModerna1 dose\n0.5 mL/50 µg2023 –2024 \nPfizer -\nBioNTech1 dose\n0.3 mL/30 µg2023 –2024 \nPfizer -\nBioNTech2 doses\n0.3 mL/30 µg2023 –2024 \nPfizer -\nBioNTech1 dose\n0.3 mL/30 µg3 or more \ndoses any \nmRNA \nvaccine\n*For information about administration intervals, people who transition from age 11 years to age 12 years during an mRNA vacci nation series, and administration \nof additional dose(s), see Table 2 in Interim Clinical Considerations for Use of COVID -19 Vaccines. COVID -19 vaccination \nstatus as of \nSeptember 2023\n▪Everyone aged 5 years and older are recommended get one 2023 –2024 COVID -19 \nvaccine to be up to date.\n▪Children aged 6 months –4 years and people who are moderately or severely \nimmunocompromised need multiple doses, including at least one 2023 –2024 COVID -\n19 vaccine dose to be up to date. \n▪People who are moderately to severely immunocompromised may get additional doses \nof the 2023 –2024 COVID -19 vaccine.Proposed 2023 –2024 COVID -19 Vaccine Up to Date \nDefinition\nSimultaneous administration of \nCOVID -19 and other vaccines\n▪In accordance with General Best Practice Guidelines for Immunization , routine \nadministration of all age -appropriate doses of vaccines simultaneously (i.e., \nadministering more than one vaccine on the same clinic day or “coadministration”) is \nrecommended for children, adolescents, and adults if there are no contraindications at \nthe time of the healthcare visit. \n–Providers may simultaneously administer COVID -19, influenza, and respiratory syncytial virus (RSV) vaccines to \neligible patients; the Health Alert Network (HAN) published on September 5, 2023 may be consulted for \nadditional information about simultaneous administration of these vaccines.\n–Simultaneous administration of COVID -19 vaccine and nirsevimab (a long -acting monoclonal antibody for certain \ninfants and young children for prevention of RSV) is recommended\n–Coadministration of COVID -19 and RSV vaccine for older adults is acceptable\n–There are additional considerations if administering an orthopoxvirus vaccine and COVID -19 vaccine Simultaneous administration of COVID -19 and other vaccines\nInterim Clinical Considerations for Use of COVID -19 Vaccines | CDC\nUse of Nirsevimab for the Prevention of Respiratory Syncytial Virus Disease Among Infants and Young Children: Recommendations ofthe Advisory Committee on Immunization \nPractices —United States, 2023 | MMWR (cdc.gov)\nHealthcare Providers: RSV Vaccination for Adults 60 Years of Age and Over | CDC\nInterim Clinical Considerations for Use of JYNNEOS and ACAM2000 Vaccines during the 2022 U.S. Mpox Outbreak | Mpox | Poxvirus | CDC", "summary": "Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. Evidence to Recommendations Framework: 2023 –2024 (Monovalent, XBB Containing) COVID -19 Vaccine Megan Wallace, DrPH, MPH ACIP Meeting  September 12, 2023 Evidence to…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-september-12-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-09-12/11-COVID-Wallace-508.pdf", "doc_date": "2023-09-12", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 150}
{"title": "12 COVID Peacock 508", "content": "Centers for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nCOVID -19 Vaccine Implementation\nGeorgina Peacock, MD, MPH\nImmunization Services Division\nCenters for Disease Control and PreventionEnsuring no -cost, timely access to the 2023 -2024 COVID -19 vaccines\nCOVID -19 activities are integral to the broader Fall respiratory virus vaccine program goals\nProtect Promote Communicate Implement\nProtect Americans \nfrom influenza, COVID -\n19, and RSVPromote vaccine \nuptake among those at \nhigher risk:\n•Older adults and \nlong -term care \nfacility residents\n•People with \nunderlying medical \nconditions\n•People who are \npregnant\n•ChildrenCommunicate new and \nrapidly changing \nrecommendations for \ninfluenza, COVID -19, \nand RSVImplement Fall \nvaccination equitably, \nincluding through the \nBridge Access Program \nfor COVID -19 VaccinesFall Respiratory Virus Vaccine Program\nCommercialization of COVID -19 Vaccines\nWhat will change\n▪Transition of federal procurement and \ndistribution of all COVID -19 vaccines to more \ntraditional public/private model\n▪End of CDC COVID -19 Provider Agreement\n▪Vaccine data reporting transitions to routine \nreporting processes for jurisdictions that \nhave signed data use agreement (DUA) with \nCDCWhat will not change\n▪Evidence -based vaccination program to \ndevelop recommendations, monitor safety \nand effectiveness, and strengthen vaccine \nconfidence\n▪CDC’s commitment to ensuring access to \nCOVID -19 vaccines at no cost\nSnapshot of COVID -19 vaccine data reporting plans\nAdministration data from reporting states National Immunization Surveys\nBridge Access Program for COVID -19 Vaccines\nOther surveillance systems\nVaccine Safety Datalink\nOther data sources\nOmnibus surveys\nInternet panel survey of pregnant people\nDistribution data\n\nPromotion and Communication\nCOVID -19 Communications will be part of a Pan -\nRespiratory Efforts\nEncourage vaccination as the first tool in our toolbox for respiratory virus season\nAdditional tools to protect yourself:\n•washing hands with soap and water\n•staying home if you are feeling sick\n•avoiding close contact with sick people\n•avoiding touching your eyes , nose, and mouth\n•Cover your mouth and nose when coughing or sneezing\n•ensuring the air around us is well -ventilated\n•wearing a mask if you’re at risk or if COVID -19 hospitalizations are high in your \narea\n•Practice good health habits, such as cleaning and disinfecting frequently \ntouched surfaces, and taking care of your health\nCommunication Components and Tactics\nHealthcare Providers:\n•Owned Media\n•Social media\n•Press release\n•Earned Media\n•Medscape article\n•Trade outlets\n•Paid (boosted) social media\n•Medical society partner outreachConsumers:\n•Owned Media\n•Social media posts\n•Earned media\n• Blanket (matte) release in English \nand Spanish\n• Op-edpiece\n•Paid media\n•TV ads in select markets\n•Boosted social media posts\n•Partner outreach and tool \nkit\n\n▪COVID -19 –Bridge Access Program\n–Audience: No -cost COVID -19 vaccines for underinsured\nand insured adults\n–Kickoff: September 2023\n–Campaign work underway\n▪COVID -19 –General\n–Kickoff: September/October 2023\n–Communication materials underway\n▪RSV\n–Kickoff: September 2023\n–Older adult vaccine with HCP recommendation and RSV immunization for infants\n–Audience: Communication materials under development with a focus on cliniciansCOVID -19 Outreach Activities\nImplementation\nResources for partners\n▪vaccines.gov\n–All sites offering COVID -19and flu vaccines\n–This week: sites offering Bridge Access Program COVID -19 vaccines\nEnsuring no -cost, timely access to COVID -19 vaccines\n▪Timely access for all\n▪Established access for those with health insurance\n▪Established access for children\n▪Ensuring no -cost access for adults\n▪Program design to maximize proximity\n▪Program design to maximize equity\nAvailability of COVID vaccine\n▪Federal contracts have been modified to allow hastened delivery of the \n2023 -2024 COVID -19 vaccines within public health infrastructure for \nchildren and adults\n•Projected first dose availability: within 48 hours of CDC \nrecommendation\n▪Contracts with participating retail pharmacies have been modified to \nallow doses with the Bridge Access Program to begin simultaneously with \ndoses offered through private insurance \n•Projected first dose availability: within 48 hours of CDC \nrecommendation\n▪Commercial insurance is expected to be available in the same timeframe\nEnsuring no -cost, timely access to COVID -19 vaccines\n▪Timely access for all\n▪Established access for those with insurance\n▪Established access for children\n▪Ensuring no -cost access for adults\n▪Program design to maximize proximity\n▪Program design to maximize equity\nInsurance plans will cover the 2023 -2024 COVID -19 \nvaccines immediately\n▪The Affordable Care Act (ACA) requires insurers to cover most ACIP -recommended \nvaccines without cost sharing by the next coverage year1\n–COVID -19 vaccines are on recommended schedules since February 20232\n▪Section 3203 of the CARES Act expedites coverage of COVID -19 vaccines beyond \nthat which is required of most preventive services\n–As of January 5, 2021: “plans and issuers must cover COVID -19 vaccines and their \nadministration without cost sharing immediately once the vaccine becomes \nauthorized under an EUA or approved under a BLA, and according to the scope of \nthe applicable EUA or BLA”3\n▪In July 2023, HHS issued guidance to payors to prepare to cover COVID -19 \nvaccination with the onset of COVID -19 vaccine commercialization4\n1. 42 U.S. Code §300gg –13 -Coverage of preventive health services. https://www.law.cornell.edu/uscode/text/42/300gg -13\n2. CDC Immunization Schedules by Age: https://www.cdc.gov/vaccines/schedules/hcp/index.html\n3. FAQs about Affordable Care Act Implementation Part 50: https://www.dol.gov/sites/dolgov/files/EBSA/about -ebsa/our -activities/resource -center/faqs/aca -part -50.pdf\n4. CMS Administrator Brooks -LaSure Letter to Payors Regarding Coverage of COVID -19 Vaccines Post Commercialization, July 13 2023: https://www.hhs.gov/about/news/2023/07/13/cms -administrator -brooks -lasure -letter -\nto-payors -regarding -coverage -covid -19-vaccines -post -commercialization.html\nPeople with Medicare and Medicaid will also have \naccess to COVID -19 vaccines at no cost \n▪COVID -19 vaccines covered under Medicare Part B without cost -sharing\n▪Inflation Reduction Act, passed in August 2022, includes key provisions:\n–Eliminates cost -sharing for all ACIP -recommended vaccines under \nMedicaid and Medicare Part D/equivalent plans\n–Guarantees that nearly 50 million Medicare beneficiaries and more than \n80 million Medicaid beneficiaries will have access to all vaccines \nrecommended by ACIP without cost -sharing\nChildren 0 through 18 years of age who meet \nat least one of the criteria:\n•Medicaid eligible\n•Uninsured, or\n•American Indian/Alaska Native, or  \n•Underinsured*VFC Program Eligibility\n* Eligible to receive vaccine only through an enrolled Federally Qualified Health \nCenter (FQHC), Rural Health Center (RHC) or a deputized provider under \nDelegation of Authority\n\n•Approximately 50% of US children\n•>$4 billion program\n•CDC distributes more than 75M doses of pediatric \nvaccine each year, the vast majority of which is \npurchased through VFC.\n•Nearly 38,000 VFC provider locations across 61 \nVFC awardee jurisdictionsVFC Program Reach\nThe VFC program has reduced racial, ethnic, and \neconomic disparities in infant immunization in the US", "summary": "Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. COVID -19 Vaccine Implementation Georgina Peacock, MD, MPH Immunization Services Division Centers for Disease Control and PreventionEnsuring no -cost, timely access to…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-september-12-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-09-12/12-COVID-Peacock-508.pdf", "doc_date": "2023-09-12", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 18}
{"title": "13 COVID Twentyman 508", "content": "Centers for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nBridge Access Program \nEnsuring no -cost, timely access to the 2023 -2024 COVID -19 \nvaccines for adults\nEvelyn Twentyman, MD, MPH\nImmunization Services Division\nCenters for Disease Control and Prevention\nWhy Do We Need the Bridge Access Program for \nCOVID -19 Vaccines?\n*Underinsured is defined here as related to vaccination coverage. \n1. Data are internal CDC estimates.This program will serve as temporary bridge to the permanent and comprehensive Vaccines for \nAdults Program proposed in the FY23 and FY24 President’s Budgets\n24.8\n7.1\n23.0\n51.0121.7Adult Population by Coverage Status (millions)1\nUninsured\nUnderinsured*\nMedicaid Enrolled (19-64)\nMedicare Enrolled\nPrivately Insured (19-64)\nThere are 25-30 million adults \n(ages 18 -64) without \ninsurance , and additional \nadults whose insurance will not \nprovide no -cost coverage for \nCOVID -19 vaccines after these \nproducts are commercialized\nEnsuring no -cost, timely access to COVID -19 vaccines\n▪Established access for those with insurance\n▪Established access for children\n▪Ensuring no -cost access for adults\n▪Program design to maximize proximity\n▪Program design to maximize equity\n▪Timely access for all\nThe analysis on which estimates of proximity are based considers a variety of provider types and locations that will \nparticipate in the Bridge Access Program . Access may increase if additional providers participate.\n•~8,000 317-enrolled providers\n•~4,500 State -funded vaccine providers\n•~1,400 HRSA -supported health centers (HRSA)\n•~21k Pharmacies\n•~10k CVS locations\n•~9k Walgreens locations\n•~2,000 eTrue North locations –number may \nincreaseProviders\nLocal Health Centers\nHealth Centers* will partner with \nstate immunization programs to \nensure access to COVID -19 vaccines \nfor uninsured adults\nHRSA will provide funding to \nparticipating HRSA -supported \nhealth centers to support services \nthat will help ensure equitable \naccess. State immunization \nprograms will design distribution of \nvaccines.Pharmacies\nPharmacies will ensure access to no -\ncost COVID -19 vaccines using their \nextensive footprints and community \npartnerships\nVaccines will be donated by \nmanufacturers to pharmacies, and \nadministration costs will be \ncovered by CDC.Existing partnerships with state and \nlocal health departments (S/LHDs) \nwill facilitate distribution of COVID -\n19 vaccines through providers in \nnetworks\nCDC will manage purchase and \ndistribution of COVID -19 vaccines\nand provide oversight and technical \nassistance. State immunization \nprograms will design distribution of \nvaccines.\nLocal Healthcare ProvidersWhere Will Vaccines Be Available Through the Bridge \nAccess Program? \n*HRSA -funded health centers and Health Center Program look -alike organizations\nWalgreens locations sourced from Walgreens Store Locator website early August 2023.\nCVS locations sourced from CVS Store Locator website early August 2023.\neTN Pharmacy vaccination locations from ICATT/ eTN early September 2023.\nHRSA Health Center COVID -19 Vaccine Program Participants (FQHCs) from HRSA early September 2023.\nProviders who received shipment of 317-funded routine adult vaccine CY21 -23 from VTrckS late July 2023.\nProviders who received shipment of State -funded routine adult vaccine CY21 -23 from VTrckS late July 2023.\nNote: Some points may not be visible due to point \noverlap. Points are displayed in order of site count from \nleast to most: top -eTN , HRSA, State, 317, Walgreens, \nCVS -bottom)\nOverall, 85% of uninsured \npopulations live <5 miles from \nBridge Access Program site :\n•Urban: 97%\n•Suburban: 59%\n•Rural: 39%\nOverall, 5% of uninsured \npopulations estimated to be \n>10 miles from Bridge Access\nProgram siteNational Proposed Bridge Access Program Site Locations\nBridge Access Program Retail Pharmacy Approaches\n▪▪CVS plans to administer doses within both their \nstorefronts and Minute clinics \n▪▪Walgreens plans to administer doses in both their \nstorefronts and at off-siteevents targeting areas of low \naccess & low uptake\n▪▪eTrueNorth is a pharmacy aggregator that \nsubcontracts with smaller pharmacies\n–Intended to reach lower -access areas without other coverage \nwithin the Bridge Access Program\n–Additional subcontract negotiations between eTrueNorth and \npossible additional participating pharmacies are ongoing\n\nEnsuring no -cost, timely access to COVID -19 vaccines\n▪Timely access for all\n▪Established access for those with insurance\n▪Established access for children\n▪Ensuring no -cost access for adults\n▪Program design to maximize proximity\n▪Program design to maximize equity\nThe Bridge Program would address leading barriers to COVID -19 vaccination:Program design to maximize equity\n•Lack of health insurance or a \nregular provider\n•Lack of proximity or \ntransportation to place of care•Inconsistent coverage across \nhealth insurance policies\n•Inconsistent outreach and \nengagement from health \nsystems •History of \ndisparities ,discriminatory \npatterns and racism\n•Rise in inaccurate \ninoformation about vaccinesAccessibility Availability Confidence\n•Providing access to COVID -\n19 vaccines for uninsured \nand underinsured adults at \nno cost•Designing for optimized \nproximity (variety of \nprovider/site types, low -access \nand low -coverage lists and \npayments)•Supporting and growing \nvaccine confidence through \npartnerships with trusted and \nwelcome messengers\nLessons learned from 2022 -2023 COVID -19 bivalent booster uptake\nCommunity -based partnerships are key \nCommunity -based organizations and other partners work with CDC, pharmacies, jurisdictions, and HRSA -supported \nhealth centers to reduce barriers to COVID -19 vaccine access and promote uptake. These partners are particularly critical to \nreaching people who are uninsured or underinsured. \nFUNDED PARTNERS\nCBOs and other funded partners will:\n• Host community outreach events to spread \nawareness of the Bridge Program\n• Work within their communities as trusted and \nwelcome messengers \n• Partner with providers to hold vaccine clinics to \nprovide greater access to vaccination\n• Develop educational materials to promote COVID -\n19 vaccination and the Bridge Program\nAll \nAmericans\n\nThe Bridge Access Program is a temporary “bridge” to \na permanent Vaccines for Adults (VFA) Program\nThe Bridge Access Program serves as a temporary solution for access to COVID -19 vaccines for adults. VFA and \nadditional 317 funding are needed to bridge the gap in equitable access to immunization across the lifespan. \n\n▪CDC’s Bridge Website\n–A central location for information and communications assets\n▪Program guides for specific implementing partners\n▪Clinician -facing calls and materials for vaccine providers\n▪Communications toolkit for partners\n–Digital toolkit for program resources and promotional materials including key messages, sample newsletter, and \ncommunications assets\n▪vaccines.gov\n–Where patients and care providers can go this week to find all sites providing no -cost COVID -19 vaccines through \nthe Bridge Access Program, as well as all other providers for COVID -19 or influenza vaccines\n▪Bridge Access Program Call Center\n–Available this week through 1 -800 -CDC -INFO\n–https://www.cdc.gov/cdc -info/index.htmlResources for partners\nFor more information, contact CDC\n1-800 -CDC -INFO (232 -4636)\nTTY:  1 -888 -232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention.\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nThank you", "summary": "Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. Bridge Access Program  Ensuring no -cost, timely access to the 2023 -2024 COVID -19  vaccines for adults Evelyn Twentyman, MD, MPH Immunization Services Division Centers…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-september-12-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-09-12/13-COVID-Twentyman-508.pdf", "doc_date": "2023-09-12", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 14}
{"title": "ACIP approach to mAbs", "content": "▪Passive immunization\n–Transfer of preformed antibody produced externally to provide protection to the \nrecipient\n–Provides temporary protection that wanes with time\n–Transfer of maternal antibody across the placenta that provides protection in early \ninfancy is an example of passive immunization\n▪Active immunization\n–Administration of specific components of an infectious agent that elicit an immune \nresponse in the recipient\n–Immunology memory provides prolonged protection that may be lifelong\n–Traditional vaccines provide active immunizationPassive and Active Immunization\n▪With development of long -acting monoclonal \nantibodies ( mAbs ), there is an opportunity to \nprovide protection beyond what can be \nprovided by traditional vaccines\n▪Especially valuable when\n–Full protection is needed without delay\n–A traditional vaccine is not available \n▪For some indications, a long -acting mAb\nmight provide “long enough” protection\n–For a respiratory disease season\n–For a critical part of a pregnancy\n–For prevention of travel -related infectionMonoclonal antibodies for \nprevention of infectious diseases\nwho -monoclonal -antibodies.jpg (2480 ×3508)\n\nCDC will prioritize for ACIP consideration those long -acting monoclonal \nantibodies for prevention of infectious diseases that are:\n▪Expected to address conditions that result in a significant burden of \ndisease to the public’s health; \n▪Not expected to present significant implementation issues –at least \nfrom the perspective of mode of administration, storage and handling, \nand frequency of administration --for immunization providers; and\n▪Expected to be priced at a level allowing for incorporation into \nimmunization programs. CDC’s Approach to Prioritizing Long -Acting Monoclonal \nAntibodies for Prevention of Infectious Diseases", "summary": "▪Passive immunization –Transfer of preformed antibody produced externally to provide protection to the  recipient –Provides temporary protection that wanes with time –Transfer of maternal antibody across the placenta that provides protection in early  infancy is an example of passive immunization ▪Active immunization –Administration of specific components of an infectious agent that elicit an immune  response in the recipient –Immunology memory provides prolonged protection that may be…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-august-3-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-08-03/ACIP-approach-to-mAbs.pdf", "doc_date": "2023-08-03", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 3}
{"title": "01 RSV Long 508", "content": "1\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nMaternal/Pediatric Respiratory Syncytial Virus (RSV) \nWork Group\nSarah S. Long, MD\nChair, Maternal/Pediatric RSV Work Group \nACIP General Meeting\nAugust 3, 2023\n\n2Work group members (External)\nACIP Members\nSarah Long (chair)\nPablo Sanchez\nOliver Brooks\nCamille KottonConsultants\nCody Meissner (Dartmouth Geisel School of Medicine)\nHelen Chu (University of Washington)\nNatasha Halasa (Vanderbilt University)\nDenise Jamieson (Emory University School of Medicine)\nDaniel Feikin (World Health Organization)\nCarol Baker (University of Texas Health Science Center)\nKevin Ault (Western Michigan University)Liaisons\nJames McAuley (IDSA)\nPatsy Stinchfield (NFID)\nBrenna L. Hughes (ACOG)\nNicole Chaisson (AAFP)\nSean O’Leary (AAP)\nJennifer Schuster (PIDS)\nMolly Howell (AIM)GRADE/ EtRConsultants\nDoug Campos -Outcalt\nRebecca MorganEx Officio Members\nRachel Zhang (FDA -CBER)\nNicholas Geagan (FDA -CBER)\nJudy Beeler (FDA -CBER)\nYodit Belew (FDA -CDER)\nPrabha Viswanathan (FDA -CDER)\nSonnie Kim (NIH -NIAID)\nApril Killikelly (Public Health Agency of Canada)\nWinnie Siu (Public Health Agency of Canada)\nValerie Marshall (OIDP/OASH)\nJessica Lee (CMS/CMCS)\nTerry Dalle -Tezze (HRSA)\nLucia Lee (FDA -CBER)\nRobin Wisch (FDA -CBER)\n3Work group members (CDC)\nAmber Winn\nChris Taylor\nTami Skoff\nAngie Campbell\nMichael Melgar\nAmanda Payne\nNicole Dowling\nNoelle Molinari\nClaire Midgley\nFiona HaversPragna Patel\nAndrea Sharma\nAmadea Britton\nRuth Link -Gelles\nDanielle Moulia\nMegan Wallace\nMonica Godfrey\nKaren Broder\nNaomi Tepper\nHeidi MolineCDC ACIP Staff\nMelinda Wharton\nStephanie Thomas\nJessica MacNeilHannah Rosenblum\nDerrell Powers\nRaigan Wheeler\nSally Ezra\nElizabeth Greene\nManisha Patel\nTom Shimabukuro\nDemorah Hayes\nLatifah BoyceCDC\nKatherine Fleming -Dutra (co -lead)\nJefferson Jones (co -lead)\nMeredith McMorrow\nMila Prill\nNatalie Thornburg\nAron Hall\nIsmael Ortega -Sanchez\nMelissa Coughlin\nJamison Pike\nLauren RoperA. Patricia Wodi\nNeil Murthy\nChristine Olson\nAnne Hause\nAndrew Leidner\nDavid Shay\nSarah Meyer\n4▪Epidemiology and burden of RSV in infants\n▪Virology and immunology of RSV\n▪Safety and efficacy of nirsevimab\n▪Cost effectiveness analysis for nirsevimab –CDC model\n▪Cost effectiveness analysis for nirsevimab –Comparison with manufacturer model\n▪Evidence to Recommendations framework for nirsevimab\n▪Clinical considerations for nirsevimabPrevious maternal/pediatric RSV ACIP presentations on \nnirsevimab\n5Agenda: Thursday August 3, 2023\n▪Evidence to Recommendations \nFramework for nirsevimab\n▪Nirsevimab implementation \nconsiderations\n▪Clinical considerations for nirsevimab\n▪Workgroup considerations and proposed \nrecommendations and voting language \n▪Vaccines for Children ResolutionDr. Jefferson Jones (CDC)\nDr. Georgina Peacock (CDC)\nDr. Jefferson Jones (CDC)\nDr. Jefferson Jones (CDC)\nDr. Jeanne Santoli (CDC)\n6\n\n7▪Infants aged <8 months born during or entering their first RSV season are \nrecommended to receive one dose of nirsevimab (50 mg for infants <5 kg and 100 \nmg for infants ≥5 kg)\n▪Children aged 8–19 months who are at increased risk of severe RSV disease and \nentering their second RSV season are recommended to receive one dose of \nnirsevimab (200 mg) Proposed ACIP Voting Language", "summary": "1 Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Maternal/Pediatric Respiratory Syncytial Virus (RSV)  Work Group Sarah S. Long, MD Chair,…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-august-3-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-08-03/01-RSV-Long-508.pdf", "doc_date": "2023-08-03", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 7}
{"title": "02 RSV jones 508", "content": "Centers for Disease Control and Prevention\nEvidence to Recommendations Framework: \nNirsevimab Updates\nJefferson Jones MD MPH FAAP , CDR USPHS\nCo-Lead, Respiratory Syncytial Virus Vaccines -Pediatric/Maternal Work Group \nCoronavirus and Other Respiratory Viruses Division\nNational Center for Immunization and Respiratory Diseases\nAugust 3, 2023\n2Evidence to Recommendations ( EtR) Framework\nPolicy Questions\n▪Should one dose of nirsevimab be recommended for infants aged <8 months born \nduring or entering their first RSV season (50 mg for infants <5 kg and 100 mg for \ninfants ≥5 kg)?\n▪Should one dose of nirsevimab be recommended children aged 8 –19 months who \nare at increased risk of severe RSV disease and entering their second RSV season \n(200 mg)?\n▪Given an average RSV season of 4 –5  months, infants aged 8 months and children \naged 20 months would be experiencing their second and third RSV seasons, \nrespectively\n3Nirsevimab is a passive immunization\n▪Active immunity results from infection or vaccination, which triggers \nanimmune response\n▪Passive immunity is when a person receives antibodies from an external \nsource\n–From mother to baby through transplacental or breastmilk transfer\n–Direct administration of antibodies, such as IVIG or monoclonal \nantibodies \nIVIG= Intravenous Immunoglobulin Therapy\nhttps://www.cdc.gov/vaccines/vac -gen/immunity -types.htm\n4Evidence to Recommendations ( EtR) Framework\nPICO Question 1\n▪Population Infants aged <8 months born during or entering their first RSV \nseason\nIntervention Nirsevimab (1 injection prior to start of RSV season or at birth if \nborn during season, 50 mg if <5 kg or 100 mg if ≥5 kg)\nComparison No nirsevimab prophylaxis\nOutcomes ▪Medically attended RSV -associated lower respiratory tract \ninfection (LRTI)\n▪RSV-associated LRTI with hospitalization\n▪RSV-associated LRTI with ICU admission\n▪RSV-associated death\n▪All-cause medically attended LRTI\n▪All-cause LRTI -associated hospitalization\n▪Serious adverse events\n5Evidence to Recommendations ( EtR) Framework\nEtRDomain Question(s)\nPublic Health Problem ▪Is the problem of public health importance?\nBenefits and Harms ▪How substantial are the desirable anticipated effects?\n▪How substantial are the undesirable anticipated effects?\n▪Do the desirable effects outweigh the undesirable effects?\nValues ▪Does the target population feel the desirable effects are large relative \nto the undesirable effects?\n▪Is there important variability in how patients value the outcome?\nAcceptability ▪Is the intervention acceptable to key stakeholders?\nFeasibility ▪Is the intervention feasible to implement?\nResource Use ▪Is the intervention a reasonable and efficient allocation of resources?\nEquity ▪What would be the impact of the intervention on health equity?\nEtRDomain: Public Health Problem\nIs RSV -associated disease among infants <8 months of age entering their \nfirst RSV season and infants born during the RSV season of public health \nimportance? \n7Changes in seasonality of RSV transmission following \nSARS -CoV2 introduction —NREVSS1, 2017 –2023\n0510152025\n27293133353739414345474951 135791113151719212325\nJul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun% PCR results RSV -positive\nEpidemiologic week2017 –18 2018 –19 2019 –20 2020 –21 2021 –22 2022 –23\nAbbreviation : PCR = polymerase chain reaction; RSV = respiratory syncytial virus. 1. https://www.cdc.gov/mmwr/volumes/72/wr/mm7214a1.htm\n* 3-week centered moving averages of percentage of RSV -positive PCR results nationwide. The black dotted line represents the thr eshold for a seasonal epidemic (3% RSV -positive laboratory PCR results). \n8Epidemiology of RSV\n▪RSV is the most common cause of hospitalization in U.S. infants\n–Highest hospitalization rates in first months of life\n–Risk declines by month with increasing age in infancy and early childhood\n▪Prematurity and other chronic diseases increase risk of RSV -associated \nhospitalization, but most hospitalizations are in healthy, term infants\n▪Work group felt that RSV -associated disease in infants born or entering their \nfirst RSV season is of public health importance\nEtRDomain: Benefits and Harms\nDo the desirable effects outweigh the undesirable effects?\n10Efficacy estimates and concerns in certainty of \nassessment\nOutcome Efficacy estimate* Concerns in certainty of assessment\nBenefits\nMedically attended RSV LRTI 79.0% (95% CI: 68.5% –86.1%) None\nRSV LRTI with hospitalization 80.6% (95% CI: 62.3% –90.1%) None\nRSV LRTI with ICU admission 90.0% (95% CI: 16.4% –98.8%) Serious (imprecision): Too few events\nDeath due to RSV respiratory \nillnessNone recorded N/A\nAll-cause medically attended -\nLRTI34.8% ( 95% CI: 23.0 –44.7%) None\nAll-cause LRTI -associated \nhospitalization44.9% ( 95% CI: 24.9% –59.6%) None\n*Pooled phase 2b (excluding underdosed) and phase 3 trial estimate comparing nirsevimab arm to placebo arm\n11Relative risk of SAEs and concerns in certainty of \nassessment\nOutcome Relative risk1 Concerns in certainty of assessment\nHarms\nSerious Adverse Events \n(SAEs)20.73 (95% CI: 0.59 –0.89) Serious (imprecision)\n1Pooled phase 2b and phase 3 estimate comparing nirsevimab arm to placebo arm\n2Adverse event resulting in death, hospitalization, significant disability, or requiring medical intervention. \nAdverse events include respiratory symptoms.\n12Summary of GRADE for nirsevimab\nOutcome​ Importance Design\n(# of studies)​Findings​ Evidence\ntype​1\nBenefits\nMedically attended RSV \nLRTICritical RCT (2)Nirsevimab is effective in preventing medically attended \nRSV LRTIHigh\nRSV-associted LRTI with \nhospitalizationCriticalRCT (2)Nirsevimab is effective in preventing medically attended \nRSV LRTI with hospitalization High\nRSV-associated LRTI with \nICU admissionCritical RCT (2)Nirsevimab is likely effective in preventing medically \nattended RSV LRTI with ICU admissionModerate\nRSV-associated death Critical RCT (2) No RSV -associated deaths reported -\nAll-cause medically \nattended LRTIImportantRCT (2) Nirsevimab is effective in preventing all cause medically \nattended LRTIHigh\nAll-cause LRTI -associated \nhospitalizationImportant RCT (2)Nirsevimab is effective in preventing all cause \nhospitalization with respiratory diseaseHigh\nHarms\nSerious adverse events​ Critical RCT (2)SAEs were likely not more common in intervention group \nthan placebo groupModerate\n13Additional safety data provided at Antimicrobial Drugs \nAdvisory Committee meeting\n▪Most commonly reported adverse reaction were injection site reactions \n(0.3%) and rash (0.9%)\n▪FDA noted an imbalance in deaths between nirsevimab and the control \narms but determined that the deaths were unlikely to be related to \nnirsevimab\nhttps://www.fda.gov/advisory -committees/advisory -committee -calendar/june -8-2023 -meeting -antimicrobial -drugs -advisory -committee -meeting -announcement -06082023\n14Nirsevimab phase 3b study (HARMONIE)1\n▪Enrolled 8,058 infants\n–Age at enrollment: 49% <3 month, 24% 3 -5 months, 28% ≥6 months\n–85% born at term, 50% born in season\n▪Conducted in France, UK, and Germany during August 8, 2022 –February 28, 2023\n▪Randomized to nirsevimab or no injection\n▪Primary endpoint RSV hospitalization\n–LRTI hospitalization with positive RSV test \n–RSV tests ordered by clinician and not on all patients with LRTI \n–Participants followed for at least 12 months after randomization\n▪At end of RSV season, preliminary efficacy results released\n–Median post -randomization follow up time of 2.5 months \n1Study not peer reviewed and information provided directly by sponsor; https://www.clinicaltrials.gov/study/NCT05437510\n15HARMONIE preliminary results1\n▪Efficacy\n–RSV hospitalization: 83% (95% CI 68% –92%)\n–Severe disease (SaO2 <90% and oxygen given): 76% (95% CI 33% –93%)\n–All-cause hospitalization with LRT I during RSV season: 58% (95% CI \n40% –71%)\n▪Safety\n–Grade 1 AEs slightly higher in nirsevimab arm (29%) vs no intervention \narm (25%)\n–Number of Grade 2 and Grade 3 AEs similar between nirsevimab and \ncontrol arm\nSaO2= oxygen saturation; AE= adverse event\n1Study not peer reviewed and information provided directly by sponsor; https://www.clinicaltrials.gov/study/NCT05437510/ . Results analyzed as of \n2/28/2023 because RSV season had ended, and median duration of follow up was 2.5 months at that time.\n16Benefits and harms summary\n▪Overall GRADE evidence rating: moderate\n▪Downgraded based on imprecision for protection against ICU admissions \nbecause of few recorded events and imprecision of SAEs because rare \nevents are unlikely to be detected\n▪The work group felt that the:\n–Desirable anticipated effects of nirsevimab were moderate to large\n–Undesirable anticipated effects of nirsevimab were minimal to small\n–Desirable effects outweighed the undesirable effects and favored \nnirsevimab over no intervention\nEtRDomain: Values\nCriterion 1: Does the target population feel that the desirable effects are \nlarge relative to undesirable effects?\nCriterion 2: Is there important uncertainty about, or variability in, how \nmuch people value the main outcomes?\n18Summary results of CDC and University of Iowa/RAND \nsurvey on RSV immunizations to prevent RSV disease in \ninfants\n▪Only 33% of respondents thought their baby ‘definitely’ or ‘probably’ \nwould get an RSV infection within one year after being born\n▪Despite being unsure or perceiving RSV risk to be low, respondents were \nworried their baby would need to be hospitalized if they got sick with RSV \n(mean response 4 of 5 with 5 being most worried)\n▪70% of respondents said they ‘definitely’ or ‘probably’ would get an RSV \nantibody injection for their baby if safe and effective*\n*If antibody injection was approved by FDA and recommended by CDC. \nCDC and University of Iowa/RAND survey, unpublished\n19Values summary\n▪The work group determined that the target population probably feels that the \ndesirable effects are large relative to undesirable effects\n▪The work group varied in whether they felt there was important uncertainty about, \nor variability in, how much people value the main outcomes\n*If antibody injection was approved by FDA and recommended by CDC. \nCDC and University of Iowa/RAND survey, unpublished\nEtRDomain: Acceptability\nIs immunization with nirsevimab acceptable to key stakeholders?\n21Acceptability Summary\n▪In a survey of U.S. pediatric providers, over 85% agreed that parents need \nmore information about RSV, that immunization could help prevent RSV, \nand that immunization policy should ensure all children get access1\n▪The American Academy of Pediatrics and National Foundation For \nInfectious Diseases Roundtable have stated the need for safe and effective \nRSV prevention products2,3\n▪The work group felt that passive immunization with nirsevimab was \nprobably acceptable to key stakeholders\n1. https://admin.allianceforpatientaccess.org/wp -content/uploads/2023/01/AfPA -and-NCfIH_The -Indirect -Impact -of-RSV_Survey -Report_Ja n-2023.pdf\n2. AAP COID BGC Pediatrics 2014 Aug;134(2):415 -20. \n3. https://www.nfid.org/wp -content/uploads/2022/04/NFID -RSV-Call-to-Action.pdf\nEtRDomain: Feasibility\nIs nirsevimab feasible to implement among all infants <8 months of age \nentering their first RSV season and infants born during the RSV season?\n23Work Group Feasibility Interpretation\n▪Considerations reviewed in separate presentation\n▪Work group felt that nirsevimab will probably be feasible to implement\nEtRDomain: Resource Use\nIs nirsevimab immunization among all infants <8 months of age entering \ntheir first RSV season and infants born during the RSV season a \nreasonable and efficient allocation of resources?\n25Updates to cost effectiveness model\n▪Cost of product \n–$495 list price\n–$395 Vaccines for Children (VFC) program price\n–Assuming 50% VFC and 50% private insurance, average price of $445\n–Price not final\n▪Mortality assumptions modified to include individuals at increased risk of \nsevere RSV disease\n▪Savings from not using palivizumab incorporated\n▪Other inputs unchanged1\n1Other inputs unchanged from previous model presented at February 23, 2023 ACIP meeting\n26Number needed to immunize with nirsevimab to \nprevent one health outcome\n17 48 128 581 \n24 194 \n - 100 200 300 400 500 600 700\nOutpatient ED Inpatient ICU Inpatient Day ICU DayNumber needed to immunize to avoid\n27Cost per health event averted\nCost of $445 per dose$2,662 $7,473 $19,909 $90,494 \n$3,687 $30,165 \n $- $10,000 $20,000 $30,000 $40,000 $50,000 $60,000 $70,000 $80,000 $90,000 $100,000\nOutpatient ED Inpatient ICU Inpatient Day ICU DayCost per Event Averted\n28Cost effectiveness result and Work Group \nInterpretation\n▪Updated base case result: $102,811 per quality adjusted life year saved\n▪The work group felt nirsevimab is or probably is a reasonable and efficient \nuse of resources\nEtRDomain: Equity\nWhat would be the impact of nirsevimab on health equity?\n30Equity Summary\n▪If recommended, ACIP will vote on VFC resolution for nirsevimab\n▪National studies of death certificates found higher rates among non -Hispanic black \nchildren compared with non -Hispanic White infants and children aged 1 –4 years1\n▪ICU admission rates for RSV among Non -Hispanic Black infants <6 months old were \n1.2–1.6x higher than among Non -Hispanic White infants2\n▪RSV hospitalization rates 4 –10x higher among Alaska Native and American Indian \nchildren aged <24 months than the rate in the general population3\n▪Studies of RSV hospitalization by race and ethnicity have differing results4–7\n▪The work group felt that nirsevimab would increase health equity\n1. Hansen J Infect Dis 2022 Aug 15;226(Suppl 2):S255 -S266. 2. Unpublished data from RSV -NET, CDC. 3. Atwell Pediatrics 2023, e2022060435. 4 . Hall Pediatrics 2013 Aug;132(2):e341 -8;5. Hall NEJM \n2009;360(6):588 –598. 6. Iwane Pediatrics 2004 Jun;113(6):1758 -64, findings differed by age group. 7. Rha Pediatrics 2020 Jul;146 (1):e20193611, findings differed by age group\n31EtRSummary: All infants 1st RSV season\nEtRDomain Question(s) Work Group Judgments\nPublic Health \nProblem▪Is RSV -associated disease among infants <8 months of age \nentering their first RSV season and infants born during the \nRSV season of public health importance?Yes\nBenefits and \nHarms▪How substantial are the desirable anticipated effects?\n▪How substantial are the undesirable anticipated effects?\n▪Do the desirable effects outweigh the undesirable effects?Moderate to large\nMinimal to small\nYes\nValues ▪Does the target population feel the desirable effects are \nlarge relative to the undesirable effects?\n▪Is there important variability in how patients value the \noutcome?Yes/probably yes\nNo consensus\nAcceptability ▪Is nirsevimab acceptable to key stakeholders? Yes/probably yes\nFeasibility ▪Is the intervention feasible to implement? Probably yes\nResource Use ▪Is the intervention a reasonable and efficient allocation of \nresources?Yes/probably yes \nEquity ▪What would be in the impact of the intervention on health \nequity?Probably increased\n32Evidence to Recommendations Framework\nSummary: Work Group Interpretations\nAll infants 1st RSV season \nBalance of\nconsequencesUndesirable\nconsequences\nclearly\noutweigh\ndesirable\nconsequences\nin most settingsUndesirable\nconsequences\nprobably\noutweigh\ndesirable\nconsequences\nin most settingsThe balance\nbetween\ndesirable \nand undesirable\nconsequences\nisclosely\nbalanced or\nuncertainDesirable\nconsequences\nprobably\noutweigh\nundesirable\nconsequences\nin most settingsDesirable\nconsequences\nclearly\noutweigh\nundesirable\nconsequences\nin most settingsThere \nisinsufficient\nevidence \ntodetermine \nthebalance of\nconsequences\nMinority opinion \n33Evidence to Recommendations Framework\nSummary: Work Group Interpretations\nAll infants 1st RSV season \nType of\nrecommendationWe do not \nrecommend the \ninterventionWe recommend \ntheintervention for \nindividuals based on \nshared \nclinical decision -\nmakingWe recommend \ntheintervention\n2ndindication\nShould one dose of nirsevimab be recommended for children 8 –19 \nmonths of age with increased risk of severe disease entering their second \nRSV season?\n35Evidence to Recommendations ( EtR) Framework\nPICO Question 2\n▪Population Children aged 8 –19 months who are at increased risk of severe RSV \ndisease and who are entering their second RSV season\nIntervention Nirsevimab ( 200 mg [2 x 100 mg] injection near start of second RSV\nseason)\nComparison No nirsevimab prophylaxis\nOutcomes ▪Medically attended RSV associated lower respiratory tract \ninfection (LRTI)\n▪Medically attended RSV associated LRTI with hospitalization\n▪Medically attended RSV associated LRTI with ICU admission\n▪RSV-associated death\n▪All-cause Medically attended LRTI\n▪All-cause LRTI associated hospitalization\n▪Serious adverse events\n36Evidence to Recommendations ( EtR) Framework\nEtRDomain Question(s)\nPublic Health Problem ▪Is the problem of public health importance?\nBenefits and Harms ▪How substantial are the desirable anticipated effects?\n▪How substantial are the undesirable anticipated effects?\n▪Do the desirable effects outweigh the undesirable effects?\nValues ▪Does the target population feel the desirable effects are large relative \nto the undesirable effects?\n▪Is there important variability in how patients value the outcome?\nAcceptability ▪Is the intervention acceptable to key stakeholders?\nFeasibility ▪Is the intervention feasible to implement?\nResource Use ▪Is the intervention a reasonable and efficient allocation of resources?\nEquity ▪What would be the impact of the intervention on health equity?\nEtRDomain: Public Health Problem\nIs RSV disease among children who are at increased risk of severe disease \nin their 2nd RSV season of public health importance?\n38Risk groups previously proposed to receive nirsevimab \nwhen entering second RSV season\n▪Based on American Academy of Pediatrics recommendations for palivizumab for a \nchild’s second RSV season1\n▪Assumed to be cost saving compared with palivizumab\n▪Proposed recommendation to receive nirsevimab when entering 2nd RSV season\n–Children with chronic lung disease of prematurity if require medical support \n(chronic corticosteroid therapy, diuretic therapy, or supplemental oxygen) during \nthe 6 -month period before the start of the second RSV season\n–Children with severe immunocompromise\n–Children with cystic fibrosis if manifestations of severe lung disease (previous \nhospitalization for pulmonary exacerbation in the first year of life or abnormalities \non chest imaging that persist when stable) or weight for length < 10th percentile\n1. American Academy of Pediatrics. Committee on Infectious Diseases [Respiratory Syncitial Virus.] In: Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH, eds.  Red Book : 2021 \nReport of the Committee on Infectious Diseases. Itasca, IL: American Academy of Pediatrics, 2021.\n39Analyses conducted by CDC to evaluate risk factors for \nsevere RSV disease during second RSV season\n▪Systematic review of literature\n▪Analysis of MarketScan national claims database\n40Systematic review of literature on risk factors for \nsevere disease during second RSV season\n▪Included any studies that compared RSV hospitalization rates among \nchildren with risk factors to a healthy control group among children aged \n6–24 months\n▪Among 3,825 abstracts, 6 studies identified\n▪Chronic lung disease, congenital heart disease, and neuromuscular disease \nanalyzed in these studies\n▪Studies indicated increased risk of hospitalization for these risk factors\n▪No studies evaluating other risk factors identified\n41Analysis of MarketScan national claims database for \nselect risk factors for severe RSV disease during second \nRSV season, 2015 -2021\n▪Using ICD -9-CM/ICD -10-CM codes, identified children with and without \nselect conditions (chronic lung disease, congenital heart disease, Down \nsyndrome, neuromuscular disease, pulmonary malformations, \nimmunodeficiency, cystic fibrosis) and children that were hospitalized with \nRSV\n▪Compared rates of RSV hospitalization among children with a chronic \nconditions to children without chronic condition\n▪Increased rates of hospitalization seen for all conditions\n▪RSV testing may be more common for children with risk conditions, \ninflating RSV -specific hospitalization rates \n42Increased incidence of RSV -associated severe disease \nin American Indian and Alaska Native children\n1 Atwell 2023 Pediatrics 2023 Jul 14;e2022060435.2Karron et al. J Infect Dis 1999.3Holman et al. Pediatrics 2004. 4Lowther et al. J Ped Infect Dis 20005American Academy of \nPediatrics. Committee on Infectious Diseases [Respiratory Syncytial Virus.] In: Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH, eds. Red Book : 2021 Report of the Committee \non Infectious Diseases. Itasca, IL: American Academy of Pediatrics, 2021 .▪Several prior studies have documented increased incidence of RSV -associated \nhospitalizations among American Indian and Alaska Native children1,2,3,4\n–One study found that rates of RSV -associated hospitalization in AI/AN children \nwere 4 -10 times average rates of U.S. children aged 12 -23 months from NVSN1\n–These studies have been conducted in specific populations and may not be \nbroadly representative of risk in all AI/AN children\n–Findings of these studies do not separate environmental, sociocultural, or other \nfactors that may increase severe disease risk\n▪Some AI/AN communities are also in remote areas that make transportation of \nchildren with severe RSV to appropriate healthcare facilities more challenging5\n43Public health problem work group interpretation\n▪Evidence for RSV burden among children aged 8 –19 months entering their \nsecond with specific risk conditions is limited\n▪The work group felt nirsevimab should be recommended to the same \ngroups that AAP recommends for palivizumab for the second RSV season\n▪The work group also felt that nirsevimab should be recommended to \nAlaska Native and American Indian children entering their second RSV \nseason\n▪The work group felt that RSV disease among children who are at increased \nrisk of severe disease1in their 2nd RSV season was of public health \nimportance\n1For groups recommended to receive palivizumab in their second RSV season by the American Academy of Pediatrics and \nAmerican Indian and Alaska Native children \nEtRDomain: Benefits and Harms\nDo the desirable effects outweigh the undesirable effects?\n45Efficacy based on extrapolation of pharmacokinetic \ndata\n▪A pharmacokinetic trial was conducted that randomized children at \nincreased risk of severe RSV disease to palivizumab or nirsevimab\n▪In the second RSV season, 220 participants received nirsevimab and 42 \nreceived palivizumab\n▪Among those that received nirsevimab, two pharmacokinetic endpoints have \nbeen reported\n–Day 150 nirsevimab concentrations compared with phase 3 (Melody) \nefficacy trial among late pre -term and term infants that showed efficacy\n–Proportion of participants that had area under the curve nirsevimab \nconcentrations above target based on efficacy trial data of 12.8 \nmg*day/ml\nDomachowske J, Madhi SA, Simões EAF, Atanasova V, Cabañas F, Furuno K, et al.  Safety of nirsevimab for RSV in infants with heart or lung disease or prematurity. New \nEngland Journal of Medicine. 2023;386(9): 892 –894. doi: 10.1056/NEJMc2112186\n46Observed nirsevimab concentrations 150 days post -dose\n▪Among recipients of \nnirsevimab, day 150 \nconcentrations higher \nin those who received \n200 mg in second RSV \nseason (labeled trial \n05) than infants who \nreceived 50mg (if <5kg) \nor 100mg (if >5kg) in \nphase 3 Melody trial \n(labeled trial 04)\nSource: FDA briefing document for Antimicrobial Drugs Advisory Committee June 8, 2023 meeting . \nThe dashed line is EC90 value of 6.8 μg/mL determined based on RSV challenge studies in cotton rat model. \nAbbreviations: CHD, hemodynamically significant congenital heart disease; CLD, chronic lung disease of prematurity; EC90, 90% effective \nconcentration; GA, gestational age. Trial 04: MELODY trial among late pre -term and term infants. Trial 05: Pharmacokinetics stud y among infants at \nincreased risk of severe RSV disease.\n47Area under the curve (AUC) nirsevimab concentration \nand safety results\n▪Among recipients of nirsevimab in second season, most had AUC \nnirsevimab concentrations above the target threshold\n–97.7% (129/132) of infants with chronic lung disease\n–100% (58/58) of infants with congenital heart disease\n▪No adverse events judged as related to nirsevimab or palivizumab in \nsecond RSV season follow up period\nSource: FDA briefing document for Antimicrobial Drugs Advisory Committee June 8, 2023 meeting\n48Summary of GRADE for nirsevimab dose for second season\nOutcome​ Importance Design\n(# of studies)​Findings​ Evidence\ntype​\nBenefits\nMedically attended (MA) \nRSV LRTICritical 1 Nirsevimab might be effective in preventing MA RSV LRTI Low\nRSV LRTI with \nhospitalizationCriticalNo available data\nRSV LRTI with ICU \nadmissionCriticalNo available data\nRSV-associated deathCriticalNo available data\nAll cause medically \nattended LRTI ImportantNo available data\nAll cause hospitalization \nwith respiratory diseaseImportantNo available data\nHarms\nSerious adverse events​ \n(SAEs)Critical 1Prevalence of SAEs was not significantly different in the \nintervention and control groupsVery low\n49Benefits and harms summary\n▪Overall evidence rating: Very low certainty (type 4)\n▪Downgraded based on indirectness because pharmacokinetic data used as \nsurrogate for efficacy, population did not include children that matches \nproposed indication, study small in size, and no placebo group was \nincluded for comparison\n▪The work group felt1that the:\n–Desirable anticipated effects were moderate\n–Undesirable anticipated effects were minimal\n–Desirable effects outweighed the undesirable effects and favored \nnirsevimab over no intervention\n1For groups recommended to receive palivizumab in their second RSV season by the American Academy of Pediatrics and \nAmerican Indian and Alaska Native children \nEtRDomains: Values, Acceptability, and \nFeasibility\n51Values summary\n▪No additional data was available for values specific to populations at \nincreased risk for severe disease\n▪The work group determined that the target population feels or probably \nfeels that the desirable effects are large relative to undesirable effects1\n▪The work group also felt that there was probably not important \nuncertainty or variability in how much people valued the main outcomes1\n1For groups recommended to receive palivizumab in their second RSV season by the American Academy of Pediatrics and \nAmerican Indian and Alaska Native children \n52Acceptability summary\n▪No additional data was available for acceptability specific to infants and \nyoung children at increased risk\n▪The work group felt that prevention with nirsevimab was, or probably was \nacceptable to key stakeholders1\n1For groups recommended to receive palivizumab in their second RSV season by the American Academy of Pediatrics and \nAmerican Indian and Alaska Native children \n53Feasibility summary\n▪Additional visit to provider might be needed for administration of \nnirsevimab prior to beginning of 2nd RSV season\n▪The work group felt that nirsevimab was probably feasible to implement \namong children aged 8–19 months at increased risk of severe RSV disease \nentering their second RSV season1\n1For groups recommended to receive palivizumab in their second RSV season by the American Academy of Pediatrics and \nAmerican Indian and Alaska Native children \nEtRDomain: Resource Use\n55Inputs to cost effectiveness model for second RSV \nseason \n▪Theoretical groups of children with increased risk created with 2x, 4x, 6x, 10x \nhigher risk than the general population aged 8 –19 months in October\n–Increased incidence of RSV -associated hospitalization and increased mortality \nper hospitalization\n–Increased incidence of RSV -associated hospitalization but held mortality per \nhospitalization constant\n–No increase in incidence of outpatient and ED visits, healthcare costs, or \nquality adjusted life years lost with RSV disease1\n▪Cost updated to $890 nirsevimab costs (2x $445/dose)\n▪Mortality estimates modified to include high -risk individuals\n▪Other inputs unchanged1\n1Same assumption as previous model presented at February 23, 2023 ACIP meeting\n56Updated cost effectiveness results for children 8–19 \nmonths entering second RSV season\nIncremental Cost -Effectiveness Ratio ($ / quality adjusted life year)\nIncreased Risk \ncategoryRSV Hospitalization incidence \nincreasedRSV hospitalization incidence and \nmortality per hospitalization increased\n1x (base) $1,557,544 $1,557,544 \n2x $1,147,756 $836,270 \n4x $726,983 $280,740 \n6x $512,337 $118,912 \n10x $294,775 $25,328 \n57Resource Use Work Group Interpretation\n▪The work group felt that nirsevimab use among children aged 8–19 \nmonths entering their second RSV season who are at increased risk of \nsevere disease1is probably a reasonable and efficient allocation of \nresources.\n1For groups recommended to receive palivizumab in their second RSV season by the American \nAcademy of Pediatrics and American Indian and Alaska Native children \nEtR Domain: Equity\n59Equity summary and Work Group interpretation\n▪Equity issues differ by chronic condition among infants and young children\n▪AI/AN children have higher hospitalization incidence rates than general population \nduring second RSV season \n▪Non-Hispanic Black and Hispanic populations higher rates of preterm birth than \nnon-Hispanic White population1\n▪The work group felt that nirsevimab use would probably increase health equity2\n1https ://www.cdc.gov/reproductivehealth/maternalinfanthealth/pretermbirth.htm\n2For groups recommended to receive palivizumab in their second RSV season by the American Academy of Pediatrics and American I ndian \nand Alaska Native children \n60Summary: Children at high risk entering 2nd RSV season\nEtRDomain Question(s) Work Group Judgments\nPublic Health \nProblem▪Is RSV disease among children 8–19 months who are at \nincreased risk of severe disease of public health importance? Yes\nBenefits and \nHarms▪How substantial are the desirable anticipated effects?\n▪How substantial are the undesirable anticipated effects?\n▪Do the desirable effects outweigh the undesirable effects?Moderate\nMinimal\nFavors nirsevimab\nValues ▪Does the target population feel the desirable effects are \nlarge relative to the undesirable effects?\n▪Is there important variability in how patients value the \noutcome?Probably yes\nProbably no\nAcceptability ▪Is nirsevimab acceptable to key stakeholders? Yes / Probably yes\nFeasibility ▪Is the intervention feasible to implement? Probably yes\nResource Use ▪Is the intervention a reasonable and efficient allocation of \nresources?$890: Probably yes\nEquity ▪What would be in the impact of the intervention on health \nequity?Probably increased\n61Evidence to Recommendations Framework\nSummary: Work Group Interpretations\nChildren at increased risk of severe disease entering 2nd RSV season1\nBalance of\nconsequencesUndesirable\nconsequences\nclearly\noutweigh\ndesirable\nconsequences\nin most settingsUndesirable\nconsequences\nprobably\noutweigh\ndesirable\nconsequences\nin most settingsThe balance\nbetween\ndesirable \nand undesirable\nconsequences\nisclosely\nbalanced or\nuncertainDesirable\nconsequences\nprobably\noutweigh\nundesirable\nconsequences\nin most settingsDesirable\nconsequences\nclearly\noutweigh\nundesirable\nconsequences\nin most settingsThere \nisinsufficient\nevidence \ntodetermine \nthebalance of\nconsequences\n1For groups recommended to receive palivizumab in their second RSV season by the American \nAcademy of Pediatrics and American Indian and Alaska Native children \n62Evidence to Recommendations Framework\nSummary: Work Group Interpretations\nChildren at increased risk of severe disease entering \n2nd RSV season1\nType of\nrecommendationWe do not \nrecommend the \ninterventionWe recommend \ntheintervention for \nindividuals based on \nshared \nclinical decision -\nmakingWe recommend \ntheintervention\n1For groups recommended to receive palivizumab in their second RSV season by the American \nAcademy of Pediatrics and American Indian and Alaska Native children \n63Acknowledgements \nMeredith McMorrow\nLauren Roper\nKatherine Fleming -Dutra\nMila Prill\nAmanda Payne\nDanielle Moulia\nMorgan Najdowski\nDavid Hutton\nJamie Pike\nIsmael Ortega -Sanchez\nAndrew Leidner\nSara Oliver\nMonica Godfrey\nEvelyn Twentyman\nRebecca Morgan\nDoug Campos -Outcalt\nSherry Farr\nKarrie Finn -DowningMelissa Glidewell\nEric Griggs\nEmilia (Emily) Koumans\nMatt Oster\nEghosa (Ivy) Oyegun\nFrancena Scott\nOlga Varechtchouk\nLori Moore\nRoua El Kalach\nEric Larson\nHarris LaTreace\nMichelle Ruslavage\nHannah Rosenblum\nJames Singleton\nCarla Black\nSarah Meyer\nDerrell Powers\nRaigan WheelerMichael Melgar\nAmadea Britton\nErica Reott\nSamuel Graitcer\nJeanne Santoli\nJill Moses\nJamie Mells\nDawona Hough\nPaul Lucas\nMichelle Banks\nArthur Bayo\nNancy Fenlon\nRebecca Miller\nElizabeth Walker\nSuzanne Johnson -DeLeon\nJoEllen Wolicki\nElizabeth Greene\nNeil MurthyPatricia Wodi\nSarah Cutchin\nElisha Hall\nSarah Schillie\nAndrew Kroger\nMelissa Barnett\nDale Babcock\nRosa Herrera\nRichard Quartarone\nStuart Myerburg\nMelissa Taylor\nSarah Morales\nBarbara Mahon\nAll members of the ACIP \nMat/Peds RSV Work Group\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the \nofficial position of the Centers for Disease Control and Prevention.\n\nBack up slides\nGRADE \nIndication: one dose of nirsevimab for infants aged <8 months born \nduring or entering their first RSV season\n67GRADE: Medically attended RSV LRTI (n=2 studies)\n▪Measures of effect\n–Efficacy: 79.0% (68.5% to 86.1%)\n–Absolute risk (using 23.1% seasonal incidence*): 177 fewer cases per 1,000 immunized \n(195 fewer to 152 fewer)\n•Number needed to immunize: 6 (5 to 7)\n–Absolute risk (using 11.0% seasonal incidence**): 86 fewer cases per 1,000 immunized \n(94 fewer to 74 fewer)\n•Number needed to immunize: 12 (11 to 14)\n–Absolute risk (using 5.4% seasonal incidence [phase 3 trial controls]): 42 fewer cases per \n1,000 immunized (46 fewer to 37 fewer)\n•Number needed to immunize: 24 (22 to 27)\n▪Concerns in certainty assessment\n–None\n▪Evidence type: High (type 1)67\n*Lively 2019 JPIDS , 5 years from 3 NVSN sites from Nov -Apr season, included if with acute respiratory infection (ARI, not \nrestricted to LRTI).  **Assumes 47.5% of ARI are LRTI ( Rainisch 2020 Vaccine )\n68GRADE: RSV -associated LRTI with hospitalization (n=2 \nstudies)\n▪Measures of effect\n–Efficacy: 80.6% (62.3% to 90.1%)\n–Absolute risk (using 1.3% seasonal incidence*): 10 fewer cases per \n1,000 immunized (12 fewer to 8 fewer)\n•Number needed to immunize: 100 (83 to 125)\n–Absolute risk (using 2% seasonal incidence [phase 3 trial controls]): 16 \nfewer cases per 1,000 immunized (18 fewer to 12 fewer)\n•Number needed to immunize: 63 (56 to 83)\n▪Concerns in certainty assessment\n–None\n▪Evidence type: High (type 1)68\n*NVSN data 2016 -2020 (unpublished), included if with ARI\n69GRADE: RSV -associated LRTI with ICU admission (n=2 \nstudies)\n▪Measures of effect\n–Efficacy: 90.0% (16.4% to 98.8%)\n–Absolute risk (using 0.35% seasonal incidence*): 3 fewer cases per \n1,000 immunized (3 fewer to 1 fewer)\n•Number needed to immunize: 317 (289 to 1,754)\n–Absolute risk (using 0.1% seasonal incidence [phase 3 trial controls]): \n0.9 fewer cases per 1,000 immunized (1.0 fewer to 0.2 fewer)\n•Number needed to immunize: 1,111 (1,010 to 6,250)\n▪Concerns in certainty assessment\n–Serious (imprecision): Too few events\n▪Evidence type: Moderate (type 2)69\n*Arriola 2019 JPIDS for proportion of hospitalizations admitted to ICU, NVSN data 2016 -2020 (unpublished), included if with ARI\n70GRADE: All -cause medically attended LRTI (n=2 \nstudies)\n▪Measures of effect\n–Efficacy: 34.8% (23.0 to 44.7%)\n–Absolute risk (using 13.9% seasonal incidence [phase 3 trial controls]): \n46 fewer cases per 1,000 immunized (60 fewer to 30 fewer)\n•Number needed to immunize: 21 (17 to 33)\n▪Concerns in certainty assessment\n–None\n▪Evidence type: High (type 1)70\n71GRADE:  All -cause LRTI -associated hospitalization (n=2 \nstudies)\n▪Measures of effect\n–Efficacy: 44.9% (24.9% to 59.6%)\n–Absolute risk (using 3.7% seasonal incidence in phase 3 controls): 16 \nfewer cases per 1,000 vaccinated (22 fewer to 9 fewer)\n•Number needed to immunize: 63 (45 to 111)\n▪Concerns in certainty assessment\n▪Evidence type: High (type 1) 71\n72GRADE: SAEs (n=2 studies)\n▪Measures of effect\n–Relative Risk: 0.73 (0.59 to 0.89)\n–Absolute risk: 28 fewer cases per 1,000 immunized (43 fewer to 12 \nfewer)\n▪Concerns in certainty assessment\n–Serious (imprecision)\n▪Evidence type: Moderate (type 2)\n72\nGRADE \nIndication: one dose of nirsevimab for children aged 8 -19 months who are \nat increased risk of severe RSV disease and entering their second RSV \nseason\n74GRADE Summary\na Very serious concern for indirectness, due to use of a surrogate outcome, the was surrogate established in 1st season while trial is in 2nd season, and population that does not match proposed indication.\nb Pharmacokinetic extrapolation was used and based on comparable pharmacokinetic levels from efficacy in infants <12 months o f age for prevention of the first medically attended RSV LRTI to pharmacokinetic levels in children ≤24 \nmonths with chronic lung disease (CLD) or congenital heart disease (CHD) entering their second RSV season. Based on pharmacok inetic and efficacy data from the phase 2b and phase 3 (MELODY) trials, a target area under the curve \nnirsevimab concentration of > 12.8 mg*day/ml was established.  For the CLD cohort, 129/132 (98%) participants met the target nirsevimab concentration, and for the CHD cohort, 58/58 (92%) participants met the target. Additionally, \nthe concentration of nirsevimab 150 days after injection was higher compared with the 150 -day concentration in the phase 3 trial nirsevimab arm population.\nc Serious concern for indirectness as the comparison group is palivizumab rather than placebo.\nd Very serious concern for imprecision due to the width of the confidence interval containing estimates for which different p olicy decisions might be considered.\ne 180 trial participants received nirsevimab in both the first and second season. 40 received palivizumab in the first season and nirsevimab in the second seasonCertainty assessment No of patientsEffect\nCertainty Importance\nNo of \nstudiesStudy \ndesignRisk of bias Inconsistency Indirectness Imprecision Other \nconsiderationsNirsevimab Palivizumab Relative \n(95% CI)Absolute \n(95% CI)\nMedically attended lower respiratory tract infection\n1 randomized \ntrialnot serious not serious not serious very seriousanone Pharmacokinetic extrapolation \nwas used and based on \ncomparable pharmacokinetic \nlevels from efficacy in infants \n<12 months of age for \nprevention of the first \nmedically attended RSV LRTI to \npharmacokinetic levels in \nchildren ≤24 months with \nchronic lung disease (CLD) or \ncongenital heart disease (CHD) \nentering their second RSV \nseasonbn/a n/a ⨁⨁◯◯\nLowCRITICAL\nSerious adverse events\n1 randomized \ntrialnot serious not serious seriouscvery seriousdnone 21/220e0/42 (0%) RR 8.4\n(0.52 to \n135.5)f86 more per \n1,000 (from 6 \nfewer to 1,000 \nmore)g⨁◯◯◯\nVery lowImportant\nUpdated cost effectiveness analysis\nEconomic Analysis of Nirsevimab in \nPediatric Populations\nDavid W. Hutton, PhD, MS\nAssociate Professor, Health Management and Policy, School of Public Health\nAssociate Professor of Global Public Health, School of Public Health\nAssociate Professor, Industrial and Operations Engineering, College of Engineering\nUniversity of Michigan\nHighlighted portions of presentation represent changes from Feb 2023 ACIP presentation \nResearch Team\nUniversity of Michigan\n•David Hutton, PhD\n•Lisa Prosser, PhD\n•Angela Rose, MPH\n•Kerra Mercon , MS•Jefferson Jones, MD, MPH, FAAP\n•Mila Prill, MSPH\n•Meredith McMorrow, MD, MPH, FAAP\n•Jamison Pike, PhD\n•Katherine Fleming -Dutra, MD, FAAP\n•Ismael Ortega -Sanchez, PhD\n•Fiona Havers, MD\n•Betsy Gunnels, MSPH\n•Andrew Leidner , PhD\n77\nConflicts of interest statements\n•Authors have no known conflict of interests.\n78\nMethods: Study question\n•Determine the cost -effectiveness of nirsevimab by:\n•Evaluating the population burden of disease in pediatric US population in \nterms of \n•annual resource utilization \n•total cases\n•total costs \n•deaths\n•quality -adjusted life years\n•Comparing the incremental cost -effectiveness ratio of nirsevimab to no \nprevention.\n•Running scenario analyses outcomes that explore key areas of \nuncertainty.\n•Perspective: Societal\n79\nMethods: Intervention(s)\n•Target population: US pediatric < 7 months of age entering their first \nRSV season\n•Secondary analysis high -risk infants in their second RSV season (7 -18 months \nold)\n•Interventions:\n1.No nirsevimab (Natural history)\n2.Nirsevimab against RSV illness\n•Time horizon: 1 RSV season\n•Analytic horizon: lifetime\n•Discount rate: 3%\n80\nMethods: Decision Tree Model\n81No \nProphylaxis\nNirsevimabInfection Hospitalization\nED\nNone of the aboveOutpatientAlive\nDeadInfection\nAdverse \nEventsSystemic Reaction\nInjection Site Reaction\nNone of the aboveSerious Adverse EventInfection Infection\nMethods: Epidemiology\nHospitalization\nBase Case Range Source\nRespiratory syncytial virus (RSV) \nincidence, per 100,000 See Above See AboveCDC NVSN, \nDecember 2016 to September 2020\nProportion with LRTI\nAge 0 -5 months 1.0 0.5-1.0 Rainisch, 2020\nAge 6 -11 months 1.0 0.5-1.0 Rainisch, 2020\n82CDC New Vaccine Surveillance Network (NVSN) hospitalization rates for children under 2 years of age from December 2016 to Sep tember 2020 - 1,000 2,000 3,000 4,000\n0 2 4 6 8 10 12 14 16 18 20 22Hospitalization rate  \nper 100,000 \nchildren\nAge in months\nMethods: Epidemiology\nED and Outpatient\nRespiratory syncytial virus (RSV) \nincidence, per 100,000 Base Case Range Source\nEmergency Department\nAge 0 -5 months 7,500 5,500 –7,500 Lively 2019 (base case and range)5, Hall \n2009 (range)6\nAge 6 -11 months 5,800 5,700 –5,800\nAge 12 -23 months 3,200 3,200 –5,300 Hall 2009 (base case and range)6, Lively \n2019 (range)5\nProportion with LRTI\nAge 0 -5 months 0.65 0.25 -1.0 Rainisch, 20204\nAge 6 -11 months 0.5 0.25 -1.0 Rainisch, 20204\nMedically attended outpatient\nAge 0 -5 months21,60013,200 –21,600 Lively 2019 (base case and range)5, Hall \n2009 (range)6\nAge 6 -11 months 24,600 17,700 –24,600\nAge 12 -23 months18,4406,600 –29,620 Jackson 2021 (base case and range)7, \nHall 2009 (range)6\nProportion with LRTI\nAge 0 -5 months 0.65 0.25 -1.0 Rainisch, 20204\nAge 6 -11 months 0.3 0.1-1.0 Rainisch, 20204\n83\nMethods: Epidemiology\nMortality\nBase \nCaseRange Source\nRSV mortality per \nhospitalization\nAge 0 -5 months0.10% 0.04 -0.20%Hansen 2022, \nDoucette 2016\nAge 6 -11 months0.10% 0.04 -0.20%Hansen 2022, \nDoucette 2016\nAge 12 -23 months 0.3%0.28% -0.34%Gupta 2016\n84New Mortality estimates are based on recent study by Hansen to be appropriate for \nthe entire US population instead of just non -high -risk individuals.\nSeasonality\n0.0%5.0%10.0%15.0%20.0%25.0%30.0%\nApr May Jun Jul Aug Sep Oct Nov Dec Jan Feb MarFraction of Annual Infections\n85\nSource: National Respiratory and Enteric Virus Surveillance System (NREVSS) (2015 -2019)\nMethods: Nirsevimab Efficacy\n0.00%10.00%20.00%30.00%40.00%50.00%60.00%70.00%80.00%90.00%100.00%\n0 2 4 6 8 10 12 14Efficacy\nMonth\n86Average efficacy first 6 \nmonths = trial efficacy \nSigmoid decay to \nfinal efficacy\nZero efficacy\nMethods: Efficacy\nVariable Base case \nvalueRange for \nsensitivity \nanalysisSource\nNirsevimab\nInitial efficacy (months 0 -5) \nagainst RSV -associated LRTI 79.0% 68.5% -86.1%\nEfficacy months 6 -10 25.0% 0.0% -50.0%\nEfficacy after 10 months 0.0%\n87\nMethods: Provision of Nirsevimab\n•Base case:\n•At birth for those born \n•October 1 –March 31\n•October for those born in \n•April (~6 -month visit)\n•June (~4 -month visit)\n•August (~2 -month visit)\n•November for those born in\n•May (~6 -month visit)\n•July (~4 -month visit)\n•September (~2 -month visit)\n•50% coverage in the population\n88\nMethods: Medical Costs\nVariable Value Range Source\nDisease -specific \nhospitalization costs (per \nhospitalization) \nAge 0 -11 months $11,487 4,804 -86,646\nBowser 2022Age 12 -23 months $11,469 4,804 -86,646\nDisease -specific ED costs \n(per ED visit)$563 544 –581 Bowser 2022\nDisease -specific \noutpatient costs (per \noutpatient visit)$82 46-118 Bowser 2022\n89•Bowser, 2022 is a systematic review using studies from 2014 -2021\n•Funded by Sanofi\n•All numbers updated to 2022 dollars using GDP Deflator\nMethods: Productivity Costs\nVariable Value Range Source\nProductivity burden of RSV \nDisease (caregiver losses)\nDays of lost productivity\nOutpatient* 2.5 0-5Fragaszy, 2018; Petrie, 2016; \nVan Wormer, 2017\nED* 2.5 0-5Fragaszy, 2018; Petrie, 2016; \nVan Wormer, 2017\nHospitalization^ 7.4 0-14\nLifetime productivity for \nthose <1 year old (lost from \ndeath)1,795,936 Grosse, 2019\n90*Productivity for outpatient and ED based on adult influenza\n^Hospitalization productivity loss = length of hospitalization + 2 days\nMethods: Intervention Cost\nVariable Value Range Source\nImmunization -related costs\nNirsevimab, per dose $445 $50-$600 Assumption\n91Both assume no additional visits, but do include costs of administrationManufacturer has suggested $495 list price and $395 for VFC\nWe assume 50% VFC*\n* 50% VFC based on:\nBenefits from Immunization During the Vaccines for Children Program Era —United \nStates, 1994 –2013\nMethods: Palivizumab\n92•Assumption: Nirsevimab policy will lead to 100% reduction in palivizumab \nuse. \n•Savings assumptions: current Palivizumab use\n–1.6% are high -risk (palivizumab -eligible)\n–75% uptake in high -risk\n–4.17 palivizumab doses/person on average\n–$1,228/palivizumab dose\nMethods: RSV \nHealth -Related Quality -of-Life\nLRTI quality adjusted life DAYS lost Base Lower (Regnier) Upper (JIVE)\nOutpatient: Child 3.1 1.8 16.6\nOutpatient: Caregiver 1.5 0 9.1\nED: Child 4.9 2.9 16.6\nED: Caregiver 2.5 0 9.1\nHospitalized: Child 6.2 3.7 26.5\nHospitalized: Caregiver 2.4 0 13.6\n93Measured in \nDays Lost\nMost \nLikely\nMethods: Additional Inputs\n•Also included nirsevimab adverse events\n•Systemic reactions\n•Injection site reactions\n•Serious adverse events\n•Medical costs\n•Productivity costs\n•Quality -adjusted life -years lost\n94\nMethods: Uncertainty analyses\n•One-way sensitivity\n•Scenarios:\n•Upper respiratory infection effect \n•Timing of administration\n•Additional Scenario:\n•High -risk children entering the second RSV season\n95\nResults: Base Case\n•Base Case:\n•Population of 1,000 births\n•50% uptake in the nirsevimab group\n•First RSV season\n•$500/dose\n•Nirsevimab only impacts LRTI\n96\nResults: Health outcomes\n97Cohort:1,000 nirsevimab and 1,000 natural history, assuming 50% uptake in nirsevimab group\nURTI -Upper respiratory tract infection; LRTI -Lower respiratory tract infection - 100,000 200,000 300,000 400,000 500,000 600,000 700,000 800,000 900,000\n Natural History  Nirsevimab  Natural History  Nirsevimab  Natural History  Nirsevimab\nOutpatient Emergency Department InpatientNumber of Events in Cohort\nURTI LRTI\nResults: Health outcomes\n98Cohort:1,000 nirsevimab and 1,000 natural history, assuming 50% uptake in nirsevimab group107,252.7\n38,204.1\n14,341.3\n3,155.177,442.9\n9,465.2\n0.020,000.040,000.060,000.080,000.0100,000.0120,000.0\nOutpatient ED Inpatient ICU Inpatient Day ICU DayEvents Averted per year\nNirsevimab\nResults: Health outcomes\n9917 48 128 581 \n24 194 \n - 100 200 300 400 500 600 700\nOutpatient ED Inpatient ICU Inpatient Day ICU DayNumber needed to Prophylax to avoid\nNirsevimab\nResults: Costs\n100Base costs of nirsevimab : $445/dose, Cost of palivizumab for high -risk included in “Natural History”Cohort: 3.66 million births, assuming 50% uptake in nirsevimab group$0$200$400$600$800$1,000$1,200$1,400$1,600$1,800$2,000\nNatural\nHistoryNirsevimab Natural\nHistoryNirsevimab Natural\nHistoryNirsevimab Natural\nHistoryNirsevimab Natural\nHistoryNirsevimab Natural\nHistoryNirsevimab\nIntervention Outpatient ED Inpatient Deaths TotalTotal Costs in Cohort\nMillions\nMedical Productivity\nResults: Health outcomes\n101Base costs of nirsevimab : $445/dose$2,662 $7,473 $19,909 $90,494 \n$3,687 $30,165 \n $- $10,000 $20,000 $30,000 $40,000 $50,000 $60,000 $70,000 $80,000 $90,000 $100,000\nOutpatient ED Inpatient ICU Inpatient Day ICU DayCost per Event Averted\nNirsevimab\nResults: QALYs lost\n102Adverse \nEventsOutpatient ED Inpatient Deaths Total Grand\nChild Caregiver Child Caregiver Child Caregiver Child Child Caregiver Total\nNatural History 7,153 3,580 3,290 1,645 807 320 1,356 12,606 5,545 18,151 \nNirsevimab 52 6,246 3,127 2,774 1,387 565 224 949 10,586 4,738 15,324 \nCohort: 3.66 million births, assuming 50% uptake in nirsevimab group\nResults: Cost -effectiveness\n103Cohort: 3.66 million births, assuming 50% uptake in nirsevimab group\nBase costs of nirsevimab : $445/dose, Cost of palivizumab for high -risk included in “Natural History” $1,550 $1,600 $1,650 $1,700 $1,750 $1,800 $1,850 $1,900\n (18,500)  (18,000)  (17,500)  (17,000)  (16,500)  (16,000)  (15,500)  (15,000)Costs \nMillions\nQALYs (lost) from RSV \nNatural History Nirsevimab\nResults: Cost -effectiveness\n104OverallCosts ($) QALYsICER ($/QALY)\nVs. NH\nNatural History 1,585,172,002 18,151 \nNirsevimab 1,875,840,158 15,324 102,811 \nCohort: 3.66 million births, assuming 50% uptake in nirsevimab group\nBase costs of nirsevimab : $445/dose, Cost of palivizumab for high -risk included in “Natural History”\nSensitivity: Tornado nirsevimab\n105Base cost of $445/dose$0 $50,000 $100,000 $150,000 $200,000 $250,000\nnirsevimab cost/dose\nDisease-specific inpatient costs (per inpatient case)  Age 0-5 months\nRSV QALYS Lost\nInitial Efficacy\nFraction Receiving Palivizumab Natural History\nRSV-related QALYs lost Outpatient Child\nProportion of RSV infections with an LRTI diagnosis Outpatient Age 0-5 months\nDisease-specific inpatient costs (per inpatient case)  Age 6-11 months\nRSV-related QALYs lost Outpatient Caregiver\nProportion of RSV infections with an LRTI diagnosis Hospitalizations Age 0-5 monthsIncremental Cost -Effectiveness Ratio\nLow High\n $- $50,000 $100,000 $150,000 $200,000 $250,000\n$0 $100 $200 $300 $400 $500 $600ICER\nTotal Cost of Nirsevimab (drug + administration)Sensitivity: Cost nirsevimab\n106Base cost of $500/dose\nResults: Alternative Scenarios\n107No Palivizumab \nSavingsPalivizumab \nSavings\nLow -Risk Mortality $205,639 $118,522 \nOverall Average Mortality $182,397 $102,811\nCohort: 3.66 million births, assuming 50% uptake in nirsevimab group\nBase costs of nirsevimab : $445/dose, Cost of palivizumab for high -risk included in “Natural History”\nScenario: Upper respiratory infection effect\n108202,821.0\n62,596.7\n14,341.3\n3,155.177,442.9\n9,465.2\n0.050,000.0100,000.0150,000.0200,000.0250,000.0\nOutpatient ED Inpatient ICU Inpatient Day ICU DayEvents Averted per year\nNirsevimab\n $- $50,000 $100,000 $150,000 $200,000 $250,000\n$0 $100 $200 $300 $400 $500 $600ICER\nTotal Cost of Nirsevimab (drug + administration)Scenario: Upper respiratory infection effect\n109 Nirsevimab is assumed to be equally efficacious in preventing upper respiratory tract infections as lower respiratory tract infections.$48,208/QALY\nScenario: Timing analysis\n110•Cost -effectiveness of an infant receiving nirsevimab as a newborn in \n•Oct-Feb\n•Oct-March\n•Oct-April\n•With varying efficacy in months 6 -10\n•0%\n•25%\n•50%\nCohort:1,000 nirsevimab and 1,000 natural history, assuming 50% uptake in nirsevimab group\n111Scenario: Timing and efficacy in months 6 -10\nVery minor differences, Slightly higher ICERs for Oct -Apr\nBase cost of $445/dose\nICER= Incremental cost -effectiveness ratio $- $20,000 $40,000 $60,000 $80,000 $100,000 $120,000\n0% efficacy 25% efficacy 50% efficacyICER\nOct-Feb Oct-Mar Oct-Apr\nHigher -risk children entering the second RSV \nseason\n112•Immunization in October (under 19 months old in October)\n•Incidence of RSV -associated hospitalization and mortality per \nhospitalization: \n•1x, 2x, 4x, 6x, 10x higher\n•Cost\n•$890 nirsevimab costs (2x $445/dose)\nCohort:1,000 nirsevimab and 1,000 natural history, assuming 50% uptake in nirsevimab group\nSecond Season, High -Risk \n11301020304050\nInpatient ICU Inpatient Days ICU DaysEvents Averted per 1000 \nChildren given nirsevimabEvents Averted\nBase 2x 4x 6x 10x\nSecond Season, High -Risk \n114Cost is $890 per overall course, 2 doses @ $445 eachIncreased \nRiskIncidenceIncidence and mortality, given \nhospitalization\n1x (base) $1,557,544 $1,557,544 \n2x $1,147,756 $836,270 \n4x $726,983 $280,740 \n6x $512,337 $118,912 \n10x $294,775 $25,328 \nLimitations\n•Model Structure\n•No risk groups\n•No dynamic transmission. No impact of the vaccine on transmission and \nindirect effects\n•Uncertain inputs\n•Nirsevimab cost \n•QALYs lost \n•Upper respiratory tract infections\n•Palivizumab utilization\n115\nSummary\n•Nirsevimab has the potential to be cost -effective\n•Results sensitive to:\n•Cost per dose (Cost -Saving –200,000 $/QALY)\n•Inpatient costs (Cost -saving –125,000 $/QALY)\n•Efficacy (45,000 –170,000 $/QALY)\n•URTI/LRTI \n•Proportion of infections with LRTI\n•Or efficacy of nirsevimab against URTI\n•QALYs lost (20,000 –200,000 $/QALY)\n•Hospitalization, Outpatient, ED\n•Child, Parent\n116URTI: Upper Respiratory Tract Infection\nLRTI: Lower Respiratory Tract Infection\nQALY: Quality -Adjusted Life -Year\nThank You\n•Please send comments to:\n•dwhutton@umich.edu\n117\nAppendix\n118\nMethods: Epidemiological model\n119SeasonalityIncidence\n•Outpatient\n•ED\n•Hospitalizations\nNirsevimab\nWaning \nProtectionHealth Effects\n• Outpatient\n• ED\n• Hospitalizations\n• Deaths\nEconomic Effects\n• Intervention\n• Disease\n• Societal\n• QALYs\n• ICERInterventionsEpidemiology\nTiming\nCost Burden/\n•Outpatient\n•ED\n•HospitalizationsHealth Economics\nHealth Burden/\n•Outpatient\n•ED\n•Hospitalizations\nMethods: Inputs\n•Incidence\n•Raw reported incidence may be underreported because of imperfect PCR \nsensitivity, so we consider an additional scenario in sensitivity analysis:\n•based on CDC Unpublished re -analysis of raw data from Zhang et al study which found \ndecreased RSV PCR sensitivity in light of paired serology testing (adjustment factor: \n87.6%).\n120\nMethods: Inputs\nVariable Value Range Source\nProbabilities of Pediatric Adverse \nEvents: Nirsevimab\nSystemic Reaction 0.005 Sanofi/AstraZeneca ACIP \ndata request\nProbability of outpatient visit \ngiven Systemic Reaction1x \nOutpatient \nVisit- Assumption; Deluca et al \n(under review)\nAnaphylaxis 0 0 –0.0000010 Sanofi/AstraZeneca ACIP \ndata request\nInjection Site Reaction 0.002 Sanofi/AstraZeneca ACIP \ndata request\nProbability of outpatient visit \ngiven Injection Site Reaction0.1 Assumption; Deluca et al \n(under review)\nSerious Adverse Event 0.000001 Prosser, 200612\n121* ISR grade 3 not reported by arm.  We assumed the ISR grade 3 rates by arm were proportional to ISR of any severity by arm. Range is \nbased on 95% CI based on binomial proportion from the base value.\nMethods: Inputs\nVariable Value Range Source\nPediatric Quality -Adjusted Life -\nYears lost due to adverse events\nSystemic reaction 0.0056 0.00051 -0.0061 Deluca et al (under \nreview)\nAnaphylaxis 0.0137 0.0135 -0.0139\nSerious Adverse Event 0.141 0.092 -0.199 (Guillain -Barre) Prosser, \n200612\n122* No SAEs were reported in the nirsevimab trial. Values in the table above are based on the incidence of Guillian -Barre syndrome \nfollowing influenza vaccination. \nMethods: Inputs\nVariable Value Range Source\nCosts due to adverse events^\nMedical Costs\nCost of outpatient visit for systemic \nreaction$313 $27 -$1,337 Marketscan unpublished; \nDeluca et al (under review)\nCost of outpatient visit for injection \nsite reaction$326 $48 -$1,101 Marketscan unpublished; \nDeluca et al (in Press)\nAnaphylaxis medical costs $7,706 $89 -$23,414 Marketscan unpublished; \nDeluca et al (In Press)\nSerious Adverse Event $36,163.76 $10372.31 -$122,145.60 Prosser, 200612\nProductivity Costs\nRecipient time for office visit (fraction \nof day)0.25\nParent time for anaphylaxis (days) 1 1-3 Shimabukuro , 202113\nDaily productivity 190 169.41 –211.03 Grosse, 201914\n123^ Costs updated to 2022$ using GDP deflator* Daily productivity rate calculated by dividing mean annual total productivity (both market and non -market) for each age group by 365.25 days\nDeluca EK, Gebremariam A, Rose A, Biggerstaff M, Meltzer MI, Prosser LA. Cost -Effectiveness of Routine Annual Influenza Vaccination by Age and Risk St atus. Vaccine. 2023. In press\nHealth -Related Quality -of-Life\n•Sources\n•Glaser (2022)\n•Estimate based on comparison of utility losses between premature children who had RSV vs. \npremature children without RSV and their caregivers\n•Used as base case for hospitalization for children and their caregivers\n•Regnier (2013) \n•Estimate QALY losses for hospitalization, ED visits, and outpatient visits for children with \npertussis \n•Use relative QALYs between hospitalization, ED, and outpatient to estimate base losses for ED \nand outpatient in base case\n•JIVE RSV Utilities Survey (2021)\n•Estimates QALY losses for hospitalization and outpatient visits for child and caregiver\n•Estimates may be impacted by COVID -related concerns about respiratory viruses\n•Inform upper bound of range\n124\nValidation\n231\n66\n8225 \n65 \n13 \n050100150200250\nOutpatient Clinic\nVisitsED Visits HospitalizationsRates of Medically -Attended RSV \n(per 1000 births)\nRainisch et al, Vaccine, 2020 JIVE model\n125\nResults: Costs\nMedical ProductivityIntervention\nOutpatient\nED\nInpatient\nTotal RSV \nMedical\nTotal Health \nSystem\nOutpatient\nED\nInpatient\nDeaths\nTotal \nProductivity\nTotal\nNatural History 225,005,528 69,409,019 137,189,260 548,601,655 755,199,934 980,205,462 356,863,932 102,733,556 59,598,851 85,770,201 604,966,541 1,585,172,002 \nNirsevimab 815,695,065 60,614,296 115,680,370 383,861,494 560,156,160 1,375,851,225 311,646,183 86,626,721 41,701,850 60,014,178 499,988,933 1,875,840,158 \n126Base cost of $445/doseCohort:entire annual US birth cohort, assuming 50% uptake in nirsevimab group", "summary": "Centers for Disease Control and Prevention Evidence to Recommendations Framework:  Nirsevimab Updates Jefferson Jones MD MPH FAAP , CDR USPHS Co-Lead, Respiratory Syncytial Virus Vaccines -Pediatric/Maternal Work Group  Coronavirus and Other Respiratory Viruses Division National Center for Immunization and Respiratory Diseases August 3, 2023 2Evidence to Recommendations ( EtR) Framework Policy Questions ▪Should one dose of nirsevimab be recommended for infants aged <8 months born  during or…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-august-3-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-08-03/02-RSV-jones-508.pdf", "doc_date": "2023-08-03", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 126}
{"title": "03 RSV Peacock 508", "content": "National Center for Immunization & Respiratory Diseases\nCenters for Disease Control and Prevention \nNirsevimab : Implementation \nConsiderations\nGeorgina Peacock, MD, MPH, FAAP\nDirector, Immunization Services Division\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention (CDC)\nImplementation Considerations\n•Definition of Vaccine\n•Cost\n•Storage and Handling\n•Hospital Dosing\n•Outpatient Dosing\n•Coding and Immunization Information Systems\n•Timing of Vaccination\n•2nd Year Vaccinations\n•Vaccine Administration\n•Safety Reporting\n•Vaccine Confidence and Demand\n\n•No statutory definition of vaccine in the statute for the Vaccines for Children (VFC) program \n(section 1928 of the Social Security Act)\n•No statutory definition of vaccine in the Affordable Care Act (section 2713 of PHS Act), or its \nimplementing regulations, which has a provision that mandates coverage of vaccine \nrecommendations included on CDC’s immunization schedules\n•CDC has determined that nirsevimab is eligible for inclusion in the childhood immunization \nschedule and Vaccines for Children programDefinition of “Vaccine”\nProgram For Distribution Of Pediatric Vaccines\nCoverage of Certain Preventive Services Under the Affordable Care Act\n•Cost of nirsevimab estimated at $495 per dose in the private sector\n•If recommended by ACIP , nirsevimab will be covered by insurance and included in \nthe VFC program\noImportance of ensuring equitable access to nirsevimab\n•However, nirsevimab cost will still be a potential implementation barrier particularly \nfor ambulatory practices\noIf nirsevimab included in VFC, practices must carry both VFC and private stock, \nwhich may be challenging for some practicesCost\n•Similar to other routine vaccines for children\n•Administered as intramuscular injection using single -dose pre -filled syringe\noCan be administered simultaneously with other childhood vaccines\n•Dosed by weight/age\no50 mg if <5 kg\no100 mg if ≥5 kg\no200 mg (2x100 mg) for high -risk children entering 2ndRSV season\n•Stored in refrigerator at 2 -8◦C\n•May be kept at room temperature (20 -25◦C) for up to 8 hoursNirsevimab Storage, Handling, and Administration\nSource: California Department of Public Health\n▪Jurisdictions may have different scope of practice statutes for who can administer \ninjectable therapeutics vs. vaccines\n▪Scan of state laws indicates that most states allow medical assistants (who frequently \nadminister vaccines) to also deliver injection drugs\noHowever, organizations may have varied practicesScope of Practice Issues\nAmerican Association of Medical Assistants\n▪Approximately 10% of birthing hospitals participate in the VFC program\n▪Bundled payment model for newborn care\noHepatitis B vaccine more feasible to cover at ~$13 –16/dose\noWill nirsevimab be included in bundled payments?\n▪Critical to ensure documentation of in -hospital nirsevimab administration in records \nsent to primary care provider\noPotential challenges entering nirsevimab in the immunization information \nsystem (IIS)\noComprehensive maternal -neonatal records will become even more critical if \nmaternal RSV vaccine is licensed and recommendedHospital Administration\nCDC Vaccine Price List\n•Communication from birthing hospital\n•Communication about maternal RSV vaccine\n•Initial investment by pediatricians –unsure on price and demand for nirsevimab nor \ndemand for new product\n•Historical lag in insurance payment for new productsOutpatient Administration\n•CPT coding and AMA decision around CPT codes —classified as a drug/therapeutic\n•Administration codes do not include a counseling component\n•Not eligible for stand -alone counseling\n•Potential challenges with recording doses in Immunization Information SystemsCoding\nPreparing Systems for Administering a Newly Authorized Vaccine\nAcross the U.S.\nTimeline represents standards for vaccines. Incorporating a MAB \ninto vaccine systems has the potential to expand timeline due to \nincreased complexity.\nCode set subscription services activate. CDSi resources \nare published. Provider & payer systems use these for \nsystem development & deployment .Data publication partners\n(FDA, CDC, formulary vendors, & AMA)\nPrepare & publish vaccine & drug code \nset files for systems development\n10-12+\nWeeks9\nWeeksBLA\nApproved\n2 \nWeeks3 \nWeeks4 \nWeeks5 \nWeeks6 \nWeeks1 \nWeek7\nWeeks\nProvider & payer systems ready to record \n& report vaccine administrationIIS systems prepare for \nnew vaccine codes\n6-12+ weeks post authorizationVaccine ready for VTrckS\nordering & distribution\n~2 weeks postauthorization8 \nWeeks\n1-4+ weeks post authorization\n1-4+ weeks postauthorization\n 1-4+ weeks post authorization\n\n•Nirsevimab coded as a therapeutic instead of vaccine could create challenges with:\noInternal provider ordering\noProvision of a vaccine record\noInteroperability/data exchange with electronic health record (EHR) and IIS\n•Forecasting (Clinical Decision -Support [CDS] for immunization)\noDosage by weight: CDS does not have access to patient weight\no2ndseason recommendations\noFuture considerations: CDS systems unable to take into account maternal \nvaccination history for forecasting for infant nirsevimab immunizationIIS and Vaccine Forecasting Considerations\n•Timing of vaccination based on RSV season\noTropical climates may have different/unpredictable seasonality when compared \nto most of continental U.S.\n•Variability in different localities\noFor example, seasonality in AK less predictable and longer duration\n•Second year dosing\noHigh risk populations\noClarifying palivizumab recommendations in the setting of nirsevimab availabilitySpecial Considerations Add Complexity\n•Reporting of suspected adverse events (AEs) more complicated for nirsevimab than \nother immunizations:\noIf nirsevimab is administered alone, suspected AEs are reported to MedWatch\noIf nirsevimab is administered simultaneously with any vaccine, suspected AEs are \nreported to the Vaccine Adverse Event Reporting System (VAERS); additional \nreporting to Medwatch not neededReporting of Adverse Events by Patients and Providers\n•Will physicians and public accept a new vaccine\n•Occurring at the same time as commercialization of COVID -19 vaccine \nand seasonal influenza administration\n•Vaccine hesitancy and anticipated need for counseling around all \nvaccines and products\n•Efforts to weaken school immunization requirements and expand \nvaccine exemptions at the state levelVaccine Confidence/Demand\n•Considerations for implementation\n•Risks during this season’s roll out\noTiming of availability of doses\noProvider hesitancy \noUptake \n•Complexity of recommendations\noHospital vs. Outpatient\noSeasonality / Timing\noLessons learned with Hepatitis A and B\n•Unintended consequencesConclusion and Discussion\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the \nofficial position of the Centers for Disease Control and Prevention.\nThank You!", "summary": "National Center for Immunization & Respiratory Diseases Centers for Disease Control and Prevention  Nirsevimab : Implementation  Considerations Georgina Peacock, MD, MPH, FAAP Director, Immunization Services Division National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention (CDC) Implementation Considerations •Definition of Vaccine •Cost •Storage and Handling •Hospital Dosing •Outpatient Dosing •Coding and Immunization Information Systems •Timing of…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-august-3-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-08-03/03-RSV-Peacock-508.pdf", "doc_date": "2023-08-03", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 16}
{"title": "04 RSV Jones 508", "content": "Centers for Disease Control and Prevention\nProposed Clinical Consideration Updates for \nNirsevimab\nJefferson Jones MD MPH FAAP , CDR USPHS\nCo-Lead, Respiratory Syncytial Virus Vaccines -Pediatric/Maternal Work Group \nCoronavirus and Other Respiratory Viruses Division\nNational Center for Immunization and Respiratory Diseases\nAugust 3, 2023\n2Timing of nirsevimab\n▪Providers should target administration1:\n–In the first week of life for infants born shortly before and during the season\n–Shortly before the start of the RSV season for infants aged <8 months\n–Shortly before the start of the RSV season for children aged 8 –19 months who \nare at increased risk of severe RSV disease\n▪Based on pre -pandemic patterns, this means nirsevimab could be administered in \nmost of the continental United States from October through the end of March\n▪Because timing of the onset, peak, and decline of RSV activity may vary, providers \ncan adjust administration schedules based on local epidemiology\n1 While optimal timing for nirsevimab administration is shortly before the season, nirsevimab may be given at any time during t he RSV season for age -\neligible infants and children who have not yet received a dose\n3Timing of nirsevimab for infants born shortly before or \nduring RSV season\n▪Nirsevimab should be administered within 1 week of birth.\n–Administration can be during the birth hospitalization or in the \noutpatient setting\n▪Infants with prolonged birth hospitalizations due to prematurity or other \ncauses should receive nirsevimab shortly before or promptly after \ndischarge \n4Tropical climates and Alaska\n▪Tropical climates may have seasonality that differs from most of the \ncontinental United States or is unpredictable \n–May include southern Florida, Hawaii, Guam, Puerto Rico, U.S. Virgin \nIslands, and U.S. -Affiliated Pacific Islands\n▪In Alaska, RSV seasonality is less predictable, and the duration of RSV \nseasons is often longer than the national average\n▪Providers in these jurisdictions should consult state, local, or territorial \nguidance on timing of nirsevimab administration\n5Coadministration with routine childhood vaccines\n▪In accordance with CDC’s general best practices for immunizations, \nsimultaneous administration of nirsevimab with age -appropriate vaccines \nis recommended\n▪In clinical trials, when nirsevimab was given concomitantly with routine \nchildhood vaccines, the safety and reactogenicity profile of the \ncoadministered regimen was similar to the childhood vaccines given alone1\n▪When coadministered , nirsevimab is not expected to interfere with the \nimmune response to vaccines2\n1FDA label for nirsevimab ; 2Espocito Front Immunol. 2021 Aug 11;12:708939. \n6Children aged 8 –19 months recommended to receive \nnirsevimab when entering their second RSV season because of \nincreased risk of severe disease \n▪Children with chronic lung disease of prematurity who required medical \nsupport (chronic corticosteroid therapy, diuretic therapy, or supplemental \noxygen) any time during the 6 -month period before the start of the second \nRSV season\n▪Children with severe immunocompromise \n▪Children with cystic fibrosis who have manifestations of severe lung \ndisease (previous hospitalization for pulmonary exacerbation in the first \nyear of life or abnormalities on chest imaging that persist when stable) or \nweight -for-length <10th percentile\n▪American Indian and Alaska Native children\n7Nirsevimab recommendations for infants and children \nat increased risk of severe RSV\n▪Nirsevimab is recommended for infants aged <8 months born during or \nentering their first RSV season, including those recommended to receive \npalivizumab by AAP1\n▪Nirsevimab is recommended for children aged 8 –19 months who are at \nincreased risk of severe RSV disease and entering their second RSV season, \nincluding those recommended to receive palivizumab by AAP1\n▪Per FDA label, children who have received nirsevimab should not receive \npalivizumab for the same RSV season2\n1American Academy of Pediatrics. Committee on Infectious Diseases [Respiratory Syncytial Virus.] In: Kimberlin DW, Barnett ED, Lynfield R, Sawyer MH, eds. Red Book \n: 2021 Report of the Committee on Infectious Diseases. Itasca, IL: American Academy of Pediatrics, 2021 .\n2FDA label for nirsevimab\n8Precautions and Contraindications\n▪Providers administering nirsevimab should follow ACIP's general best \npractice guidelines for immunization1\n▪Nirsevimab should not be administered to persons with a history of severe \nallergic reaction (e.g., anaphylaxis) after a previous dose or to a product \ncomponent (contraindication) \n1 For immunization information systems, state or local guidance should be followed\n9Consumers and health care providers reporting \nsuspected adverse reactions for nirsevimab\n▪Report suspect adverse reactions following the administration of \nnirsevimab without coadministration with any vaccine to MedWatch \n–Reports can be submitted to MedWatch online at \nwww.fda.gov/medwatch or by phone at 1 -800-FDA-1088\n▪Report suspect adverse reactions following co -administration of nirsevimab \nwith any vaccine to the Vaccine Adverse Event Reporting System (VAERS)\n–Please specify that the patient received nirsevimab on the VAERS form, \nspecifically, in Section 9: ‘Prescriptions, over -the-counter medications, \ndietary supplements, or herbal remedies being taken at the time of \nvaccination’\n10Acknowledgements \nMeredith McMorrow\nLauren Roper\nKatherine Fleming -Dutra\nMila Prill\nAmanda Payne\nDanielle Moulia\nMorgan Najdowski\nDavid Hutton\nJamie Pike\nIsmael Ortega -Sanchez\nAndrew Leidner\nSara Oliver\nMonica Godfrey\nEvelyn Twentyman\nRebecca Morgan\nDoug Campos -Outcalt\nSherry Farr\nKarrie Finn -DowningMelissa Glidewell\nEric Griggs\nEmilia (Emily) Koumans\nMatt Oster\nEghosa (Ivy) Oyegun\nFrancena Scott\nOlga Varechtchouk\nLori Moore\nRoua El Kalach\nEric Larson\nHarris LaTreace\nMichelle Ruslavage\nHannah Rosenblum\nJames Singleton\nCarla Black\nSarah Meyer\nDerrell Powers\nRaigan WheelerMichael Melgar\nAmadea Britton\nErica Reott\nSamuel Graitcer\nJeanne Santoli\nJill Moses\nJamie Mells\nDawona Hough\nPaul Lucas\nMichelle Banks\nArthur Bayo\nNancy Fenlon\nRebecca Miller\nElizabeth Walker\nSuzanne Johnson -DeLeon\nJoEllen Wolicki\nElizabeth Greene\nNeil MurthyPatricia Wodi\nSarah Cutchin\nElisha Hall\nSarah Schillie\nAndrew Kroger\nMelissa Barnett\nDale Babcock\nRosa Herrera\nRichard Quartarone\nStuart Myerburg\nMelissa Taylor\nSarah Morales\nBarbara Mahon\nAll members of the ACIP \nMat/Peds RSV Workgroup\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the \nofficial position of the Centers for Disease Control and Prevention.\n\nCenters for Disease Control and Prevention\nWorkgroup Considerations and Voting \nLanguage for Nirsevimab\nJefferson Jones MD MPH FAAP , CDR USPHS\nCo-Lead, Respiratory Syncytial Virus Vaccines -Pediatric/Maternal Work Group \nCoronavirus and Other Respiratory Viruses Division\nNational Center for Immunization and Respiratory Diseases\nAugust 3, 2023\n13Safety monitoring for nirsevimab\n▪FDA will monitor safety reports submitted by patients, providers, and the \nmanufacturer to the FDA Adverse Event Reporting System (FAERS) and \nVaccine Adverse Event Reporting System (VAERS)\n▪FDA will monitor other data sources, including the scientific literature, \napplicant’s periodic safety reports, ongoing clinical studies, and potentially \nother sources (e.g., medical billing and electronic health records)\n▪CDC will monitor reports submitted to VAERS that involve simultaneous \nadministration of nirsevimab with childhood vaccines and will also monitor \nthe safety of nirsevimab in the Vaccine Safety Datalink (VSD)\nJune 8, 2023 Meeting of the Antimicrobial Drugs Advisory Committee -FDA Presentations\n14Effectiveness monitoring for nirsevimab\n▪ CDC will leverage existing COVID -19 vaccine effectiveness (VE) platforms\n▪ New Vaccine Surveillance Network (NVSN)\n–Active surveillance network for acute respiratory infection at 7 pediatric medical centers that \ncan assess effectiveness against outpatient and emergency department visits and \nhospitalization\n–Capture nirsevimab receipt through parent interview, medical record review at the primary \ncare provider and birth hospital, and state immunization information systems (IIS)\n▪ Virtual SARS -CoV-2, Influenza, and Other respiratory viruses Network (VISION)\n–Multi -site, electronic healthcare record -based network that can assess effectiveness against \nemergency department/urgent care visits, hospitalization, and critical illness\n–Nirsevimab effectiveness analyses will be limited to integrated healthcare system sites that will \nhave more complete capture of nirsevimab receipt (i.e., through IIS linkage and claims data)\n▪ CDC will monitor nirsevimab effectiveness throughout the season, but end of season estimates will \nlikely be most accurate. Power to estimate effectiveness depends on uptake and RSV incidence\n15RSV genomic surveillance\n▪Mutations resulting in nirsevimab resistance have been rarely reported1,2\n▪Sanofi and AstraZeneca sponsoring INFORM -RSV, a global genomic \nsurveillance study in children aged < 5 years to monitor evolution of RSV \nstrains, F protein antigenic sites, and their relationships with clinical \nfeatures of RSV disease3\n▪CDC planning genomic RSV surveillance of pediatric and adult RSV \nspecimens, including whole genomic surveillance\n–Will monitor for changes in F protein that might result in nirsevimab \nresistance\n1Ahani et al. Nat Comm 2023 14:4347; 2Wilkins et al. Lancet Infect Dis 2023; 23: 856 –66; 3Tabor 2020 Dec 17;59(1):e01828 -20.\n16Work Group considerations for infants aged <8 months \nborn during or entering RSV season\n▪Nirsevimab is safe and effective in reducing the risk of RSV disease, including \nhospitalization due to RSV\n▪Shared concerns as outlined in implementation considerations presentation\n▪Use of nirsevimab would be a reasonable and efficient allocation of resources \n–Many work group members prefer lower cost per dose\n17Work Group considerations for children aged 8 –19 \nmonths who are at increased risk of severe RSV disease \nand entering their second RSV season \n▪Limited efficacy and safety data for the use of nirsevimab for children in their \nsecond RSV season\n▪Limited data on the burden of severe disease in the second RSV season for children \nwith chronic conditions\n▪Support recommendation of nirsevimab being given to children aged 8 –19 months \nwho are entering their second RSV season for those who are recommended for \npalivizumab by American Academy of Pediatrics in their second RSV season and for \nAmerican Indian and Alaska Native children\n18Proposed ACIP Voting Language\n▪Infants aged <8 months born during or entering their first RSV season are \nrecommended to receive one dose of nirsevimab (50 mg for infants <5 kg \nand 100 mg for infants ≥5 kg)\n▪Children aged 8–19 months who are at increased risk of severe RSV disease \nand entering their second RSV season are recommended to receive one \ndose of nirsevimab (200 mg) \nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the \nofficial position of the Centers for Disease Control and Prevention.", "summary": "Centers for Disease Control and Prevention Proposed Clinical Consideration Updates for  Nirsevimab Jefferson Jones MD MPH FAAP , CDR USPHS Co-Lead, Respiratory Syncytial Virus Vaccines -Pediatric/Maternal Work Group  Coronavirus and Other Respiratory Viruses Division National Center for Immunization and Respiratory Diseases August 3, 2023 2Timing of nirsevimab ▪Providers should target administration1: –In the first week of life for infants born shortly before and during the season –Shortly…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-august-3-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-08-03/04-RSV-Jones-508.pdf", "doc_date": "2023-08-03", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 19}
{"title": "01 RSV Adults Kotton 508", "content": "Centers for Disease Control and Prevention\nAdult Respiratory Syncytial Virus (RSV) Session\nCamille Kotton, MD\nChair, Adult RSV Work Group\nAdvisory Committee on Immunization Practices (ACIP)\nJune 21, 2023\n2Adult RSV Work Group Membership\nACIP Voting Members\nCamille Kotton (Chair)\nKeipp Talbot\nSarah Long\nEx Officio Members\nRachel Zhang (FDA)\nJudy Beeler (FDA)\nNicholas Geagan (FDA)\nNadine Peart Akindele (FDA)\nSonnie Kim (NIH/NIAID)\nJeffrey Kelman (CMS)\nValerie Marshal (OIDP)CDC Co-Leads\nMichael Melgar\nAmadea Britton\nConsultants\nRobert Atmar (Baylor College of \nMedicine)\nHelen Chu (University of Washington)\nPeter Donofrio (Vanderbilt University)\nMarie Griffin (Vanderbilt University)Cynthia Lucero -Obusan (Veterans Health \nAdmin.)\nTracy Ruckwardt (NIH/NIAID)\nJonathan Temte (University of Wisconsin)\nLiaisons\nKenneth Schmader (AGS)\nVidya Sundareshan (ACP)\nGretchen LaSalle (AAFP)\nApril Killikelly (NACI, PHAC)\nWinnie Su (NACI, PHAC)Katherine Williams (APTR)\nRuth Lynfield (NFID)\nJennifer Heath (AIM)\nSteven Pergam (IDSA)\n3CDC Contributors\nCoronavirus and Other Respiratory \nViruses Division\nLauren Roper\nFiona Havers \nMeredith McMorrow\nDiya Surie\nJennifer DeCuir\nMila Prill\nAmanda Payne\nNatalie Thornburg\nMelissa Coughlin\nJefferson Jones\nKatherine Fleming -Dutra\nIsmael Ortega SanchezImmunization Safety Office\nAnne Hause\nDavid Shay\nChristine Olson\nImmunization Services Division\nNeil Murthy\nPatricia Wodi\nAndrew Leidner\nJamison Pike\n4Recap of Adult RSV session, February 2023\n▪Economic analysis of RSV vaccination in older adults (CDC model)\n▪Comparison of economic analyses of RSV vaccination in older adults (CDC \nmodel vs. industry models)\n▪Evidence to Recommendations framework for use of two RSV vaccines \n(GSK and Pfizer products) in older adults \n5Recent work group discussion\n▪Review of Season 2 safety and efficacy data from main phase 3 trials of RSV \nvaccines, as well as coadministration study results (with influenza vaccines)\n▪Update to GRADE and Evidence to Recommendations for both RSV \nvaccines, inclusive of Season 2 data\n▪Update to economic analyses of RSV vaccination in older adults, inclusive \nof Season 2 data\n▪Ethics considerations of different RSV vaccine policy recommendations\n6Recent work group discussion\n▪Possible policy recommendations for RSV vaccination of U.S. older adults\n–Should RSV vaccines be recommended for U.S. adults aged ≥65 years?\n–Should RSV vaccines be recommended for U.S. adults aged 60 –64 \nyears?\n7Agenda: Wednesday June 21, 2023\n▪ Pfizer safety and efficacy update, including coadministration \nresults\n▪ GSK safety and efficacy update, including coadministration \nresults\n▪ Economic analysis of RSV vaccination among U.S. older \nadults\n▪ Comparison of RSV vaccination economic analyses \nperformed by U. Michigan/CDC, Pfizer, and GSK\n▪ Update to Evidence to Recommendations framework for \nPfizer and GSK RSV vaccines\n▪ Clinical considerations for use of RSV vaccines in U.S. older \nadultsDr. Alejandra Gurtman (Pfizer)\nDr. Leonard Friedland (GSK)\nDr. David Hutton (U. Michigan)\nDr. Ismael Ortega Sanchez (CDC)\nDr. Michael Melgar (CDC)\nDr. Amadea Britton ( CDC)", "summary": "Centers for Disease Control and Prevention Adult Respiratory Syncytial Virus (RSV) Session Camille Kotton, MD Chair, Adult RSV Work Group Advisory Committee on Immunization Practices (ACIP) June 21, 2023 2Adult RSV Work Group Membership ACIP Voting Members Camille Kotton (Chair) Keipp Talbot Sarah Long Ex Officio Members Rachel Zhang (FDA) Judy Beeler (FDA) Nicholas Geagan (FDA) Nadine Peart Akindele (FDA) Sonnie Kim (NIH/NIAID) Jeffrey Kelman (CMS) Valerie Marshal (OIDP)CDC Co-Leads Michael…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/01-RSV-Adults-Kotton-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 8}
{"title": "02 RSV Adults Gurtman 508", "content": "Breakthroughs that change patients’ lives 1 ConfidentialAlejandra Gurtman, MD, FIDSA\nPresentation to ACIPJune 21, 2023RSVpreF Older Adults\nClinical Development Program\nUpdates\n2 Confidential WRDM Worldwide Medical & SafetyABRYSVOTM(Respiratory Syncytial Virus Vaccine)\nFDA Approval on 5/31/2023RSVpreF Older Adult \n–Clinical Development Program Updates\nIndication\nActive immunization for the prevention of lower respiratory tract disease (LRTD) \ncaused by respiratory syncytial virus (RSV) in individuals 60 years of age and older\nAdditional Clinical Trial Data\n•RENOIR –End-of -Season 1 and Mid-Season 2 analyses\n•RSVpreF/influenza vaccine coadministration study\n3 Confidential WRDM Worldwide Medical & SafetyRENOIR \n–Phase 3 safety and efficacy study in adults ≥ 60 years of age\n38,863 participants enrolled\nHealthy or with stable chronic conditions\nRandomized 1:1 to receive\nRSVpreF 120 μg or placebo\nStratified by age group\n60−69 years |70−79 years |≥ 80 years \n\n4 Confidential WRDM Worldwide Medical & SafetyDay 1 D ay 7 Month 1 Month 6 End Season 1 Start Season 2 End Season 2RENOIR Study Design \nReactogenicity \nSubset\n(n = 7,169)Local Reactions\nSystemic Events\nImmunogenicity \nSubset\n(n = 1,050)All Participants\n(N = 36,127) Safety: SAEs, NDCMCsSafety: Unsolicited AEs\nWeekly active surveillance for acute respiratory symptoms Weekly active surveillance for acute respiratory symptoms \ne e\nAE, adverse event; NDCMC, newly diagnosed chronic medical condition; SAE, serious adverse event\nDay 1 Day 7 Month 1 Month 6 End Season 1 Start Season 2 End Season 2RENOIR Study Design \nReactogenicity \nSubset\n(n = 7,169)Local Reactions\nSystemic Events\nImmunogenicity \nSubset\n(n = 1,050)All Participants\n(N = 36,127) Safety: SAEs, NDCMCsSafety: Unsolicited AEs\nWeekly active surveillance for acute respiratory symptoms Weekly active surveillance for acute respiratory symptoms \ne e\nSeason 1 Mid-Season 2\n5 Confidential WRDM Worldwide Medical & SafetyAE, adverse event; NDCMC, newly diagnosed chronic medical condition; SAE, serious adverse event\nDay 1 Day 7 Month 1 Month 6 End Season 1 Start Season 2 End Season 2RENOIR Study Design \nReactogenicity \nSubset\n(n = 7,169)Local Reactions\nSystemic Events\nImmunogenicity \nSubset\n(n = 1,050)All Participants\n(N = 36,127) Safety: SAEs, NDCMCsSafety: Unsolicited AEs\nWeekly active surveillance for acute respiratory symptoms Weekly active surveillance for acute respiratory symptoms \ne e\nSeason 1 Mid-Season 2\nAverage Time \nsince VaccinationNorthern and Southern Hemispheres Northern Hemisphere\n13.9 months\n6 Confidential WRDM Worldwide Medical & SafetyAE, adverse event; NDCMC, newly diagnosed chronic medical condition; SAE, serious adverse event\nEfficacy against RSV -LRTD \n–Demonstrated through Mid-Season 2 Analysis\nNumber of Events\nRSVpreF Placebo\nSeason 1 (N = 36,127) 15 43\nMid-Season 2 (n = 20,019) 23 4565.1%\n48.9%\n0 20 40 60 80 100\nVaccine Efficacy (%, 95% CI)RSV-LRTD with ≥ 2 symptoms\nMid-Season 2 includes Northern Hemisphere only (US, Canada, Finland) through January 31, 2023Number of Events\nRSVpreF Placebo\nSeason 1 (N = 36,127) 2 18\nMid-Season 2 (n = 20,019) 3 1488.9%\n78.6%\n0 20 40 60 80 100\nVaccine Efficacy (%, 95% CI)RSV-LRTD with ≥ 3 symptoms\n7 Confidential WRDM  Worldwide Medical & Safety\nPersistent VE against RSV -LRTD with ≥ 3 Symptoms \nthrough Mid-Season 2\nCumulative Events\nRSVpreF 0 1 1 1 2 3 3 4 5\nPlacebo 0 5 12 15 17 20 24 27 32\n40\n30\n20\n10\n0\n1 74 119 186 235 306 353 417 519\nStudy DayCases\nRSVpreFPlacebo\n8 WRDM  Worldwide Medical & SafetyRSV-LRTD, lower respiratory tract disease due to RSV; RSV, respiratory syncytial virus; VE, vaccine efficacy.\n\n9 WRDM  Worldwide Medical & SafetyPersistent VE against RSV -LRTD with ≥ 2 Symptoms \nthrough Mid-Season 2\nCumulative Events\nRSVpreF 0 5 8 10 12 18 24 31 38 38\nPlacebo 0 13 23 31 40 45 57 72 87 88\n100\n60\n40\n20\n0\n1 64 119 176 233 293 349 404 519\nStudy Day467Cases80\nRSVpreFPlacebo\nRSV-LRTD, lower respiratory tract disease due to RSV; RSV, respiratory syncytial virus; VE, vaccine efficacy.\n10 Confidential WRDM Worldwide Medical & SafetyAdverse Events, by Category, from Vaccination through 1 -Month \nFollow Up Visit and through Data Cutoff (31Jan2023): Safety Population\nAdverse Event Category​RSVpreF\nN =18,575Placebo\nN= 18,288\n​n(%) ​(95% CI) ​n(%) ​(95% CI)\nFrom Vaccination through 1-Month Fol low-Up Visit \nAny Event 1,976 (10.6) (10.2, 11.1) 1,897 (10.4) (9.9, 10.8)\n​Related 259 (1.4) (1.2, 1.6) 178 (1.0) (0.8, 1.1)\n​Immed iate AE 37 (0.2) (0.1, 0.3) 33 (0.2) (0.1, 0.3)\n​Severeor life-threatening 102 (0.5) (0.4, 0.7) 95 (0.5) (0.4, 0.6)\nFrom Vaccination through 31Jan2023\nNDCMC 806 (4.3) (4.1, 4.6) 825 (4.5) (4.2, 4.8)\nSAE 790 (4.3) (4.0, 4.6) 746 (4.1) (3.8, 4.4)\nRelated SAE 3 (<0.1) (0.0, 0.1) 0 (0.0, 0.0)\nAE leading to withdrawal 12 (<0.1) (0.0, 0.1) 11 (<0.1) (0.0, 0.1)\n100 (0.5) (0.4, 0.7) 104 (0.6) (0.5, 0.7) A\nE leading to death\nAny reactogenicity reported as adverse events (from either reactogenicity subset or non- reactogenicity subset) during the specif ied time period are included in this table.\nImmediate AE refers to an AE reported in the 30- minute post -vaccination observation period. \nAE, adverse event; NDCMC, newly diagnosed chronic medical condition; SAE, serious adverse event.\n11 Confidential WRDM Worl dwide Medical & SafetyAdverse Events, by Category, from Vaccination through 1 -Month \nFollow Up Visit and through Data Cutoff (31Jan2023): Safety Population\nAdverse Event Category​RSVpr\neF\nN =18,575Placebo\nN= 18,288\n​n(%) ​(95% CI) ​n(%) ​(95% CI)\nFrom Vaccinati on through 1 -Month Follow -Up Visit \n​Any Event 1,976 (10.6) (10.2, 11.1) 1,897 (10.4) (9.9, 10.8)\n​Related 259 (1.4) (1.2, 1.6) 178 (1.0) (0.8, 1.1)\n​Immediate AE 37 (0.2) (0.1, 0.3) 33 (0.2) (0.1, 0.3)\n​Severe or life -threatening 102 (0.5) (0.4, 0.7) 95 (0.5) (0.4, 0.6)\nFrom Vaccinati on through 31Jan2023\nNDCMC 806 (4.3) (4.1, 4.6) 825 (4.5) (4.2, 4.8)\nSAE 790 (4.3) (4.0, 4.6) 746 (4.1) (3.8, 4.4)\nRelated SAE 3 (<0.1) (0.0, 0.1) 0 (0.0, 0.0)\nAE leading to wi thdrawal 12 (<0.1) (0.0, 0.1) 11 (<0.1) (0.0, 0.1)\nAE leading to death 100 (0.5) (0.4, 0.7) 104 (0.6) (0.5, 0.7)\nAny reactogenicity reported as adverse events (from either reactogenicity subset or non- reactogenicity subset) during the specif ied time period are included in this table.\nImmediate AE refers to an AE reported in the 30- minute post -vaccination observation period. \nAE, adverse event; NDCMC, newly diagnosed chronic medical condition; SAE, serious adverse event.\n12 WRDM  Worldwide Medical & SafetyRSVpreF/influenza vaccine coadministration study\n13 WRDM  Worldwide Medical & SafetyPhase 3 Study Design and Key ProceduresRSVpreF/SIIV Coadministration in Adults ≥ 65 Years of Age\n•Placebo-controlled, double-blind study\n•Assessing safety and immunogenicity \n(non- i\nnferiority)\n•Australia (31 sites)\n•~1,400 healthy participants ≥ 65 years of age\n•Randomized 1:1\n•SIIV: Fluad Quadrivalent\n•Tim\neframe: April 13, 2022 –October  12, 2022RSVpreF\nPlacebo\nPlacebo\nRSVpreFRSVpreF/influenza vaccine \ncoadministration\nCoadministration Group (n ≈ 700)\nSequential Administration Group (n ≈ 700)Visit 3 Visit 2 Visit 1\n(~ 1 month after Visit 2) (~ 1 month after Visit 1)\nSIIV, seasonal inactivated influenza vaccineSIIV\nSIIV\n14 WRDM  Worldwide Medical & SafetyCoadministration\n(RSVpreF + SIIV) / Placebo \n(N = 703)\nn (%)Sequential Administration\n(Placebo + SIIV) / RSVpreF \n(N = 696)\nn (%)Total\n(N = 1,399)\nn (%)\nSex\nFemale 398 (56.6) 372 (53.4) 770 (55.0)\nAge at Visit 1 (years)\nMean (SD) 70.7 (4.7)                                  70.7 (4.7) 70.7 (4.7)\nMedian 70.0 70.0 70.0\nMin, max (65, 91) (65, 88) (65, 91)\nAge group at Visit 1\n65-74 years 567 (80.7) 559 (80.3) 1126 (80.5)\n≥ 75 years 136 (19.3) 137 (19.7) 273 (19.5)\nRace\nWhite 669 (95.2) 665 (95.5) 1,334 (95.4)\nAsian 22 (3.1) 21 (3.0) 43 (3.1)\nMultiracial 4 (0.6) 1 (0.1) 5 (0.4)\nOther 4 (0.6) 4 (0.5) 8 (0.6)\nNot reported or unknown 4 (0.6) 5 (0.7) 9 (0.6)DemographicsRSVpreF/influenza vaccine \ncoadministration\nSIIV, seasonal inactivated influenza vaccine\nWRDM  Worldwide Medical & Safety 15Geometric Mean Ratios with 95% CIs –Evaluable RSV Immunogenicity Population and \nEvaluable SIIV Immunogenicity Population\n.\nGMRs and 2- sided confidence intervals (CIs) calculated by exponentiating the mean difference of the logarithms of the titers (coadministration minus sequential -administration) and corresponding \nconfidence intervals (CIs) (based on Student’s t distribution).\nGMR, geometric mean ratio; GMT, geometric mean titer; HAI, hemagglutination inhibition assay; NT, neutralizing titer; RSV, respi ratory syncytial virusNon-inferiority Demonstrated \nby SIIV HAI and RSV Neutralizing Titer GMRs\nComparison, by SIIV/RSV Subgroup GMR (95% CI)\nSIIV: HAI: H1N1 A/Victoria 0.86 (0.769, 0.963)\nSIIV: HAI: H3N2 A/Darwin 0.77 (0.680, 0.866)\nSIIV: HAI: B/Austria 0.90 (0.789, 1.019)\nSIIV: HAI: B/Phuket 0.87 (0.779, 0.964)\nRSVpreF: NT: RSV A 0.86 (0.785, 0.951)\nRSVpreF: NT: RSV B 0.85 (0.766, 0.943)\n0.667 1.0 1.5\nGMT RatioRSVpreF/influenza vaccine \ncoadministration\n16 WRDM  Worldwide Medical & SafetySimilar HAI Titer Seroprotection and Seroconversion at 1 Month \nin Coadministration and Sequential Administration Groups\nCoadministration \n(RSVpreF + SIIV)/PlaceboSequential Administration \n(Placebo + SIIV)/RSVpreF\nSerostatus, Strain % (95% CI) % (95% CI)\nSeroprotection1\n1 month after vaccination\nH1N1 A/Victoria 91.6 (89.3, 93.6) 94.3 (92.3, 95.9)\nH3N2 A/Darwin 87.9 (85.2, 90.3) 91.0 (88.6, 93.0)\nB/Austria 85.3 (82.4, 87.9) 89.5 (87.0, 91.7)\nB/Phuket 88.4 (85.7, 90.7) 92.6 (90.4, 94.4)\nSeroconversion2\nH1N1 A/Victoria 36.6 (32.9, 40.3) 43.9 (40.1, 47.7)\nH3N2 A/Darwin 58.8 (55.0, 62.6) 62.6 (58.9, 66.3)\nB/Austria 39.5 (35.8, 43.3) 47.3 (43.5, 51.1) \nB/Phuket 25.3 (22.1, 28.8) 28.0 (24.6, 31.5)\n1Seroprotection:  HAI titer ≥ 1:40\n2Seroconversion: ≥ 4- fold rise from before to after receipt of SIIV if the HAI titer is ≥1:10 before SIIV or if the after SIIV HAI titer is ≥ 1:40 where the before SIIV is <1:10RSVpreF/influenza vaccine \ncoadministration\n17 WRDM  Worldwide Medical & SafetyParticipants reporting local reactions by maximum severity within 7 days after each vaccination0102030405060708090100\nVaccine as Administered1.3%\n10.1%0.7%\n7.6%0.9%6.5%0.9%\n11.5%0.9%2.1%0.1%0.6%0.1%0.3%0.9%0.7%0.9%2.1%0%\n0.3%0%\n0.1%0.1%0.6%1.2%Injection Site Pain Redness Swelling\n% of Participants\nLocal r\neactions evaluated on the arm receiving RSVpreF/placebo; no assessment of local reactogenicity at SIIV injection site.\nLocal reactions after RSVpreF had median onset 2 to 3 days after vaccination and median duration of 1 to 2 days\nOnly 1 severe local reaction reported (swelling), in the sequential administration group at Visit 2Local Reactions Mostly Mild or ModerateRSVpreF/influenza vaccine \ncoadministration\nSIIV, seasonal inactivated influenza vaccine\n18 Confidential WRDM  Worldwide Medical & SafetySystemic Events Mostly Mild or Moderate\n0.9%\n13.7%\n15.4%0.3%\n11.3%15.6%\n7.5%\n10.1%0.6%7.0%\n11.5%0.1%5.8%\n13.7%0.6%6.1%\n14.3%0.1%4.6%\n10.4%0.1%5.4%\n10.6%\n0.6%0.4%0.1%0.4%0.1%0.3%0.1%1.0%0.4%2.7%4.4%0.3%1.2%4.6%1.0%3.7%1.2%4.2%2.0%6.1%0.1%1.2%4.9%1.5%3.2%0.3%1.5%4.5%0.1%5.6%\n10.1% 4.8%7.5%2.1%6.9%0.1%3.5%5.8%0.4%4.3%6.8%3.5%5.8%2.2%5.1%0.1%2.8%4.2%0.4%0.3%1.1%0.3%0.3%0.9%0.1%0.7%0.1%1.0%\nFatigue Fever Headache Vomiting Nausea Diarrhea Muscle Pain Joint Pain\n*Vaccine as Administered100\n90\n80s70pant60ci i t\n50ar  P of\n40 %\n302010\n0\nRSVpreF/influenza vaccine \ncoadministration\nParticipants reporting systemic events by maximum severity within 7 days after each vaccination\nSystemic events after RSVpreF+SIIV had median onset 2 to 4 days after vaccination and median duration of 1 to 2 days\nSIIV, seasonal inactivated influenza vaccine\n19 WRDM  Worldwide Medical & SafetyAdverse Events, by Category, within One Month \nafter Vaccination: Safety PopulationRSVpreF/influenza vaccine \ncoadministration\nAdverse Event CategoryRSVpreF+SIIV\n(N = 703)Placeb o+SIIV\n(N = 695)Placeb o\n(N = 689)RSVpreF\n(N = 691)\n​n(%) ​n(%) ​n(%) ​n(%)\nAny event 154 ( 21.9) 134 ( 19.3) 117 (17.0) 115 (16.6)\nRelated 9 (1.3) 3 (0.4) 3 (0.4) 5 (0.7)\nSerious 8 (1.1) 6 (0.9) 2 (0.3) 5 (0.7)\nRelated 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0)\nDeath 0 (0.0) 1 (0.1) 0 (0.0) 0 (0.0)\nImmediate 3 (0.4) 1 (0.1) 1 (0.1) 0 (0.0)\nAny reactogenicity reported as adverse events (from either reactogenicity subset or non- reactogenicity subset) during the specif ied time period are included in this table.\nImmediate AE refers to an AE reported in the 30- minute post -vaccination observation period. \nAE, adverse event; NDCMC, newly diagnosed chronic medical condition; SAE, serious adverse event; SIIV, seasonal inactivated i nfluenza vaccine.\n20 Confidential WRDM Worldwide Medical & SafetyRSVpreF Older Adult Clinical Development Program Updates \n–Conclusions\n•Favorable overall safety profile of RSVpreF\n•RSVpreF remained efficacious in prevention of \nRSV-LRTD\n•Through end of season 1\n•In mid-season 2\n•Average 13.9 months of follow up since vaccination•RSVpreF safe and well tolerated when \ncoadministered with influenza vaccine\n•Non-inferior immune responses when RSVpreF coadministered with influenza \nvaccineRENOIR Phase 3 Pivotal Efficacy\n–Season 1 and Mid -Season 2RSVpreF Coadministration with \nInfluenza Vaccine\n21 Confidential Breakthroughs that change patients’ livesThank you", "summary": "Breakthroughs that change patients’ lives 1 ConfidentialAlejandra Gurtman, MD, FIDSA Presentation to ACIPJune 21, 2023RSVpreF Older Adults Clinical Development Program Updates 2 Confidential WRDM Worldwide Medical & SafetyABRYSVOTM(Respiratory Syncytial Virus Vaccine) FDA Approval on 5/31/2023RSVpreF Older Adult  –Clinical Development Program Updates Indication Active immunization for the prevention of lower respiratory tract disease (LRTD)  caused by respiratory syncytial virus (RSV) in…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/02-RSV-Adults-Gurtman-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 21}
{"title": "03 RSV Adults Friedland 508", "content": "CO-1\nGSK’s RSVPreF3 OA Vaccine (AREXVY)\nAREXVY was approved by FDA on May 3, 2023, and is indicated for the prevention \nof LRTD caused by RSV in adults 60 and older, as a single dose.\nACIP June 21, 2023\nLeonard Friedland, MD\nVice President, Scientific Affairs and Public Health  \nPresentation by GSK at ACIP June 21, 2023\n\nCO-2\nPresentation Overview\nEfficacy and safety results over 2 full RSV seasons from pivotal Phase 3 Study\n▪1 dose of AREXVY provides durable efficacy against RSV -associated LRTD over 2 full\nRSV seasons, including against severe RSV disease, in adults with underlying \ncomorbidities, and across advancing ages\n▪2nddose 12 months after 1stdose does not appear to confer additional efficacy in \noverall population\nImmunogenicity and safety results from 2 co -administration trials with influenza \nvaccines (adjuvanted, high dose) \n▪AREXVY can be administered with all types of commonly used influenza vaccines\nLRTD: lower respiratory tract disease Presentation by GSK at ACIP June 21, 2023\n\nCO-3\nPivotal Efficacy and Safety Study ( AReSVi -006): \nResults Through 2 Full RSV Seasons\nPhase 3, randomized, placebo -controlled, multi -country study to \ndemonstrate efficacy and safety of single and annual revaccination \ndoses in adults 60 years and older \nPresentation by GSK at ACIP June 21, 2023\nCO-4\nOngoing AReSVi -006 Phase 3 Trial Design\nRandomized, placebo -controlled, observer -blind, multi -country efficacy study\nAdults\n≥ 60 years\nN = 24,966\nAREXVY\n(annual group, dose 2)\nPlacebo\n(AREXVY single dose)R\nAREXVY\nN = 12,4 67\nPlacebo \nN = 12,499Season 1\n2021 –2022Season 2\n2022 –2023Season 3\n2023 –2024\nR\nAREXVY \n(annual group, dose 3)\nPlacebo\n(AREXVY single dose)\nStudy Initiated May 2021\n(Northern hemisphere)End of S2 Analysis\nMar 2023\nEnd of S1 Analysis\nApr 2022\nPlacebo\nPlacebo\n*RT-PCR confirmed; †LRTD defined as ≥ 2 lower respiratory symptoms/signs for ≥ 24 hours including ≥1 lower respiratory sign OR ≥ 3 lower \nrespiratory symptoms for ≥ 24 hours; RT -PCR: reverse transcriptase polymerase chain reactionConfirmatory secondary endpoint: Evaluate efficacy of AREXVY in prevention of RSV* -LRTD†in adults ≥ 60 YOA\nover 2 seasons, following a single dose of AREXVY and following annual revaccination dose\n▪All RSV -LRTD cases adjudicated by independent external adjudication committee\n▪Success criterion: lower limit of 2 -sided 97.5% CI for vaccine efficacy > 20%Mid-S2 Analysis Nov \n2022AReSVi -006 \nPresentation by GSK at ACIP June 21, 2023\nCO-5\nAReSVi -006 Case Definitions\nARI\n≥ 2 respiratory  \nsymptoms or signs\nOR\n≥ 1 respiratory \nand 1 systemic \nsymptom or sign for \nat least 24 hours Respiratory symptoms or signs\n▪Fever/feverishness\n▪Fatigue\n▪Body aches\n▪Headache\n▪Decreased appetiteUpper respiratory  \nsymptoms or signsLower respiratory \nsymptomsLower respiratory \nsignsSystemic \nsymptoms or signs\n▪Sputum\n▪Cough\n▪Dyspnea▪Wheezing\n▪Crackles/rhonchi\n▪Tachypnea\n▪Hypoxemia\n▪O2 supplement▪Nasal congestion\n▪Sore throat\nLRTD*\n≥ 2 lower respiratory symptoms \nor signs \n(≥ 1 sign) \nOR\n≥ 3 lower respiratory symptoms \nfor at least 24 hours ▪Sputum\n▪Cough\n▪DyspneaLower respiratory \nsymptomsLower respiratory \nsigns\n▪Wheezing\n▪Crackles/rhonchi\n▪Tachypnea\n▪Hypoxemia\n▪O2 supplement\nSevere LRTD*\n≥ 2 lower respiratory signs\nOR\nepisode preventing normal, \neveryday activitiesLower respiratory \nsigns\n▪Wheezing\n▪Crackles/rhonchi\n▪Tachypnea\n▪Hypoxemia\n▪O2 supplementAReSVi -006 \nPresentation by GSK at ACIP June 21, 2023 *USPI case definitions\nCO-6\nAREXVY Produces Durable Vaccine Efficacy Against RSV -LRTD \nOver 2 Full SeasonsAReSVi -006 \nMedian \nFollow -Up\n(months)AREXVY Placebo\nVE\n(95% CI)VE\n(95% CI) Number of events \nSingle DoseW/o season \nas covariate#W/ season \nas covariate¶\nSeason 1*\nVE 16.7 7 / 12,466 40 / 12,49482.6%\n(57.9, 94.1)82.6%\n(57.9, 94.1)\nMid Season 2 \nPost dose 114 15 / 12,469 85 / 12,49880.9%#\n(66.7, 89.8)77.3%¶\n(60.2, 87.9)\nSeason 2 Only\nPost dose 26.4 20 / 4,991 91 / 10,03156.1% \n(28.2, 74.4)56.1% \n(28.2, 74.4)\nSeason 1 + 2** 18 30 / 12,469 139 / 12,49874.5%#\n(60.0, 84.5)67.2%¶\n(48.2, 80.0)\nAnnual (2 doses, ~12 months apart)\nSeason 2 Only\nPost dose 26.4 20 / 4,966 91 / 10,03155.9% \n(27.9, 74.3)55.9% \n(27.9, 74.3)\nSeasons 1 + 2** 18 30 / 12,469 139 / 12,49874.5%#\n(60.0, 84.4)67.1%¶\n(48.1, 80.0)\n0 20 40 60 80 100Modified exposed set\n*96.95% CI for VE 1 ;**97.5% CI for Season 1 + 2 Presentation by GSK at ACIP June 21, 2023\nCO-7\nAREXVY Produces Durable Vaccine Efficacy Against \nRSV-Severe LRTD Over 2 Full SeasonsAReSVi -006 \nPresentation by GSK at ACIP June 21, 2023Modified exposed set\n*96.95% CI for VE 1 ;**97.5% CI for Season 1 + 2Median \nFollow -Up\n(months)AREXVY Placebo\nVE\n(95% CI)VE\n(95% CI) Number of events \nSingle DoseW/o season \nas covariate#W/ season \nas covariate¶\nSeason 1*\nVE 16.7 1 / 12,466 17 / 12,49494.1%\n(62.4, 99.9)94.1%\n(62.4, 99.9)\nMid Season 2 \nPost dose 114 4 / 12,469 33 / 12,49886.8%#\n(63.0, 96.6)84.6%¶\n(56.4, 96.1)\nSeason 2 Only\nPost dose 26.4 5 / 4,991 28 / 10,03164.2% \n(6.2, 89.2)64.2% \n(6.2, 89.2)\nSeason 1 + 2** 18 7 / 12,469 48 / 12,49882.7%#\n(61.6, 93.4)78.8%¶\n(52.6, 92.0)\nAnnual (2 doses, ~12 months apart)\nSeason 2 Only\nPost dose 26.4 5 / 4,966 28 / 10,03164.1% \n(5.9, 89.2)64.1% \n(5.9, 89.2)\nSeasons 1 + 2** 18 7/12,469 48/ 12,49882.7%#\n(61.6, 93.4)78.8%¶\n(52.5, 92.0)\n0 20 40 60 80 100\nCO-8\nAREXVY Produces Durable Vaccine Efficacy Against RSV -LRTD in \nVulnerable Populations Over 2 Full Seasons\nVaccine efficacy in frail participants cannot be concluded due to low number of cases accrued  AREXVY PlaceboVE\n(95% CI)VE\n(95% CI) Number of events \nSeason 1* \n(Median follow -up = 6.7 months)\n≥ 1 pre -existing \ncomorbidity of interest1 / 4,937 18 / 4,86194.6%\n(65.9, 99.9)94.6%\n(65.9, 99.9)\nPre-frail 1 / 4,792 14 / 4,77892.9%\n(53.4, 99.8)92.9%\n(53.4, 99.8)\nSingle dose over 2 seasons† \n(Median follow -up = 18 months)W/o season \nas covariate#W/ season \nas covariate¶\n≥ 1 pre -existing \ncomorbidity of interest16 / 4,983 72 / 4,91974.5%#\n(55.7, 86.1)66.7%¶\n(41.8, 82.0)\nPre-frail 8 / 4,794 47 / 4,77980.0%#\n(57.3, 91.8)73.3%¶\n(42.4, 89.2)\n0 20 40 60 80 100\nComorbidities of interest include chronic obstructive pulmonary disease, asthma, any chronic respiratory or pulmonary disease, and chronic heart failure \n(cardiorespiratory condition) and diabetes mellitus type 1 or type 2 and advanced liver or renal disease (endocrine or metabo liccondition\n*April 2022 analysis; †From 15 days post Dose 1 up to end of Season 2 in Northern HemisphereAReSVi -006 \nPresentation by GSK at ACIP June 21, 2023\nCO-9\nAREXVY PlaceboVE\n(95% CI)VE\n(95% CI) Number of events \nSeason 1* \n(Median follow -up = 6.7 months)\n≥ 60 YOA*** 7 / 12,466 40 / 12,49482.6% \n(57.9, 94.1)82.6% \n(57.9, 94.1)\n60 –69 YOA 4 / 6,963 21 / 6,97981.0%\n(43.6, 95.3)81.0%\n(43.6, 95.3)\n70 –79 YOA 1 / 4,487 16 / 4,48793.8%\n(60.2, 99.9)93.8%\n(60.2, 99.9)\nSingle dose over 2 seasons† \n(Median follow -up = 18 months)W/o season \nas covariate#W/ season \nas covariate¶\n≥ 60 YOA**** 30 / 12,469 139/ 12,49874.5%#\n(60.0, 84.5) 67.2%¶\n(48.2, 80.0)\n60 –69 YOA 17/ 6,963 74/ 6,98172.9%#\n(53.7, 85.0)65.4%¶\n(40.4, 80.9)\n70 –79 YOA 9 / 4,489 55/ 4,48980.7%#\n(60.6, 91.6)74.9%¶\n(48.4, 89.2)AREXVY Produces Durable Vaccine Efficacy Against RSV LRTD \nAcross Advancing Ages Over 2 Full Seasons\nVaccine efficacy in adults ≥ 80 years of age cannot be concluded due to low number of cases accrued  0 20 40 60 80 100\n*April 2022 analysis; ***96.95% CI; ****97.5% CI; YOA: years of age; \n†From 15 days post Dose 1 up to end of Season 2 in Northern HemisphereAReSVi -006 \nPresentation by GSK at ACIP June 21, 2023\nCO-10\nAREXVY Produces Durable Vaccine Efficacy Against RSV -A LRTD \nand RSV -B LRTD Over 2 Full Seasons\n*April 2022 analysis; †From 15 days post Dose 1 up to end of Season 2 in Northern HemisphereAReSVi -006 \nPresentation by GSK at ACIP June 21, 2023AREXVY PlaceboVE\n(95% CI)VE\n(95% CI) Number of events \nSeason 1* \n(Median follow -up = 6.7 months)\nRSV-A 2/ 12,466 13/ 12,49484.6%\n(32.1, 98.3)84.6%\n(32.1, 98.3)\nRSV-B 5/ 12,466 26/ 12,49480.9%\n(49.4, 94.3)80.9%\n(49.4, 94.3)\nSingle dose over 2 seasons† \n(Median follow -up = 18 months)W/o season \nas covariate#W/ season \nas covariate¶\nRSV-A 6/ 12,469 48/ 12,49885.2%#\n(65.4, 94.8)80.5%¶\n(54.0, 93.2)\nRSV-B 24/ 12,469 90/ 12,49868.5%#\n(50.2, 80.8)59.7%¶\n(35.8, 75.5)\n0 20 40 60 80 100\nCO-11\nReactogenicity Profile of 2ndDose in Line with 1stDose\nSolicited AEs Reported Within 4 Days of Vaccination (Solicited Safety Set)\nAREXVY Season 1 n=879; Placebo Season 1 n=878; 2 doses Season 2 n=326 (received AREXVY in Season 1 and Season 2); \n1 dose Season 2 n=345 (received AREXVY in Season 1 and Placebo  in Season 2); \nPlacebo Season 2 n=666 (received Placebo in Season 1 and Season 2)AReSVi -006: Season 2 \nPresentation by GSK at ACIP June 21, 2023Local Systemic8.1\n1.19.8\n0.9 0.160.9\n9.352.1\n9.0 7.66.0\n0.87.1\n0.3 0.318.0\n6.416.9\n5.8 7.233.7\n16.130.1\n12.8 12.0\n2.00.31.80.3 0.627.2\n12.622.1\n12.29.029.0\n8.225.2\n5.87.8\n020406080100\nRSVPreF3 OA\nPlacebo\nAnnual\n1 dose\nPlacebo\nRSVPreF3 OA\nPlacebo\nAnnual\n1 dose\nPlacebo\nRSVPreF3 OA\nPlacebo\nAnnual\n1 dose\nPlacebo\nRSVPreF3 OA\nPlacebo\nAnnual\n1 dose\nPlacebo\nRSVPreF3 OA\nPlacebo\nAnnual\n1 dose\nPlacebo\nRSVPreF3 OA\nPlacebo\nAnnual\n1 dose\nPlacebo\nRSVPreF3 OA\nPlacebo\nAnnual\n1 dose\nPlacebo\nRSVPreF3 OA\nPlacebo\nAnnual\n1 dose\nPlacebo\nErythema Pain Swelling Arthralgia Fatigue Fever Headache MyalgiaAREXVY\nAREXVY\nAREXVY\nAREXVY\nAREXVY\nAREXVY\nAREXVY\nAREXVY2 doses AREXVY\n(1st& 2ndseason)1 dose AREXVY (1stseason) \n/ Placebo (2ndseason)Placebo\n(1st& 2nd season)1 dose AREXVY \n(1stseason)Season 22 doses\n2 doses\n2 doses\n2 doses\n2 doses\n2 doses\n2 doses\n2 doses% of \nParticipants\nCO-12\nSafety Profile of 2ndDose in Line with 1stDose\nUnsolicited AEs, SAEs, fatal SAEs, and pIMDs\nAREXVY Season 1 n=12,467; Placebo Season 1 n=12,499; 2 doses Season 2 n=4,966 (received AREXVY in Season 1 and Season 2); 1 d oseSeason 2 n=4,991 \n(received AREXVY in Season 1 and Placebo in Season 2); Placebo Season 2 n=10,033 (received Placebo in Season 1 and Season 2)\nDLP: data lock point; pIMD :potential immune -mediated diseaseAReSVi -006 \nPresentation by GSK at ACIP June 21, 2023Unsolicited AEs\nWithin 30 daysSAEs\nUp to 6 months post \nvaccinationUp to DLP (Season 2)pIMDs Fatal SAEs33.0\n17.828.5\n15.8 14.9\n4.2 4.0 4.2 4.4 4.6\n0.4 0.5 0.4 0.5 0.4 0.3 0.3 0.3 0.4 0.3\n020406080100\nAREXVY\nPlacebo\n2 doses\n1 dose\nPlacebo\nAREXVY\nPlacebo\n2 doses\n1 dose\nPlacebo\nAREXVY\nPlacebo\n2 doses\n1 dose\nPlacebo\nAREXVY\nPlacebo\n2 doses\n1 dose\nPlacebo% of \nParticipants\n2.0 1.3 2.2 1.1 1.2Grade 32 doses AREXVY\n(1st& 2ndseason)1 dose AREXVY (1stseason) \n/ Placebo (2ndseason)Placebo\n(1st& 2nd season)1 dose AREXVY \n(1stseason)Season 2\nCO-13\nInfluenza Vaccine Co -administration Studies: \nImmunogenicity and Safety\nOpen -label, randomized, controlled, multi -country studies to evaluate immune \nresponse, safety, and reactogenicity of AREXVY when co -administered with \ninfluenza vaccines in adults aged 60 years and above (RSV OA=ADJ -007) or \n65 years and above (RSV OA=ADJ -008 and RSV OA=ADJ -017)\nPresentation by GSK at ACIP June 21, 2023\nCO-14\nPhase 3 Influenza Vaccine Co -Administration Studies: Designs1−3\nOpen -label, randomized controlled studies evaluating immunogenicity, safety, and \nreactogenicity of AREXVY co -administered with: \n▪FLU-QIV (RSV OA=ADJ -007; Southern hemisphere)1\n▪FLU-QIV-HD (RSV OA=ADJ -008; Northern hemisphere)2\n▪FLU-aQIV (RSV OA=ADJ -017; Europe)3\nCo-Ad group: Participants receiving single dose of RSVPreF3 OA investigational vaccine and single dose of FLU vaccine at Visit 1 . Control group: Participants \nreceiving a single dose of FLU vaccine at Visit 1 (Day 1), followed by a single dose of the RSVPreF3 OA investigational vacci ne at Visit 2. FLU-aQIV : adjuvanted \nquadrivalent influenza vaccine; FLU -QIV: quadrivalent influenza vaccine; FLU -QIV-HD: quadrivalent influenza vaccine -high dose. 1. ClinicalTrials.gov, 2022. \nNCT04841577. https://clinicaltrials.gov/ct2/show/NCT04841577 ; 2. ClinicalTrials.gov, 2023. NCT05559476. https://clinicaltrials.gov/ct2/show/NCT05559476 ; \n3. ClinicalTrials.gov, 2023. NCT05568797. https://clinicaltrials.gov/ct2/show/NCT05568797 .  Accessed May 2023\nCo-administration \n(AREXVY + FLU)\nOlder Adults\nFLU-QIV: ≥ 60 YOA\nN = 8681\nFLU-QIV-HD: ≥ 65 YOA \nN = 1,0082\nFLU-aQIV: ≥ 65 YOA \nN = 1,0263\nControl \n(FLU)\nVisit 1\n(Day 1)Visit 2 \n(Day 31)Day 61R\nControl\n(AREXVY)\nCo-Ad\nControl \nCo-Ad\nSafety Monitoring \nthrough 6 monthsBlood sampling\nAREXVY\nFLU\nPresentation by GSK at ACIP June 21, 2023\n\nCO-15\nCo-Administration of AREXVY and Licensed FLU -QIV-HD\n*RSV -A preliminary, final results pending\nFlu response evaluated using HI and RSV response evaluated using NAb (ED 60); HI: Hemagglutination RSV OA=ADJ -008: FLU QIV -HD\nAntibodyCo-Ad\nNControl\nNGMT Ratio (Control Over Co -Administration)\n1 Month After Vaccination\nPer Protocol SetGMT Ratio\n(95% CI)\nFlu A/Darwin H3N2 458 4410.98\n(0.84, 1.14)\nFlu A/Victoria H1N1 452 4350.93\n(0.80, 1.08)\nFlu B/Austria/Victoria 458 4410.95\n(0.88, 1.03)\nFlu B/Phuket/Yamagata 456 4410.92\n(0.84, 1.02)\nRSV-A* 459 3581.18 \n(1.04, 1.35)\nRSV-B 459 3571.02 \n(0.89, 1.16)\n0.5 1 1.5\nPresentation by GSK at ACIP June 21, 2023Success Criteria: Upper limit ≤ 1.5 of 2 -sided 95% CI for Group GMT Ratio (Control Group divided by Co -Ad Group) \nfor RSV vaccine and for each of FLU vaccine strains\nCO-16\nCo-Administration of AREXVY and Licensed Flu -Adjuvanted QIV \n*Lower HI titers observed than expected, investigation ongoing; **RSV -A preliminary, final results pending\nFlu response evaluated using HI and RSV response evaluated using NAb (ED 60); HI: Hemagglutination RSV OA=ADJ -017: FLU aQIV\nPresentation by GSK at ACIP June 21, 2023Success Criteria: Upper limit ≤ 1.5 of 2 -sided 95% CI for Group GMT Ratio (Control Group divided by Co -Ad Group) \nfor RSV vaccine and for each of FLU vaccine strainsAntibodyCo-Ad\nNControl\nNGMT Ratio (Control Over Co -Administration)\n1 Month After Vaccination\nPer Protocol SetGMT Ratio\n(95% CI)\nFlu A/Darwin H3N2* 433 4021.31\n(1.13, 1.52)\nFlu A/Victoria H1N1 424 3981.03\n(0.91, 1.18)\nFlu B/Austria/Victoria 433 4020.97\n(0.89, 1.05)\nFlu B/Phuket/Yamagata 432 4021.04\n(0.95, 1.12)\nRSV-A** 475 3770.98\n(0.87, 1.11)\nRSV-B 473 3771.16\n(1.03, 1.31)\n0.5 1 1.5 2\nCO-17\nModified Set: Solicited Local AEs Within 4 Days Post Vaccination\nGrade 3: > 100 mm for erythema and swelling; Grade 3 pain: significant pain at rest; prevents normal everyday activities. Fever: temperature ≥ 38.0 C/100.4 F \nby any route (oral, axillary or tympanic); Grade 3 fever: > 39.0 C/102.2 F.\nGrade 3 headache, fatigue, myalgia, arthralgia: preventing normal activity4.0% 4.6%47.0%\n42.5%\n4.5% 5.6%\n0% 0%1.2% 0.5%\n0% 0.2%\n020406080100\nCo-Ad\nVisit 1FLU\nVisit 1Co-Ad\nVisit 1FLU\nVisit 1Co-Ad\nVisit 1FLU\nVisit 1FLU-QIV-HD \nErythema SwellingPain\n4.3% 4.3%55.6%\n46.3%\n4.0% 4.3%\n0.2% 0.3%2.1%0.3%0% 0.3%020406080100\nCo-Ad\nVisit 1AREXVY\nVisit 2Co-Ad\nVisit 1AREXVY\nVisit 2Co-Ad\nVisit 1AREXVY\nVisit 2AREXVY\nErythema Swelling\n% of \nParticipantsPainRSV OA=ADJ -008: FLU QIV -HD\nPresentation by GSK at ACIP June 21, 2023Co-Ad Grade 3 FLU AREXVY\nCO-18\nExposed Set: Solicited Local AEs Within 7 Days Post Vaccination\n4.5% 3.7%51.7%\n44.8%\n3.9% 4.3%\n0% 0%0.2% 0%0% 0%020406080100\nCo-Ad\nVisit 1FLU\nVisit 1Co-Ad\nVisit 1FLU\nVisit 1Co-Ad\nVisit 1FLU\nVisit 1FLU-aQIV\nErythema Swelling Pain\n11.8%9.5%65.9%\n58.8%\n8.7%6.0%\n1.9% 1.3%0.6% 0.2%1.0% 0.7%020406080100\nCo-Ad\nVisit 1AREXVY\nVisit 2Co-Ad\nVisit 1AREXVY\nVisit 2Co-Ad\nVisit 1AREXVY\nVisit 2AREXVY\nErythema Swelling\n% of \nParticipantsPainRSV OA=ADJ -017: FLU aQIV\nGrade 3: > 100 mm for erythema and swelling; Grade 3 pain: significant pain at rest; prevents normal everyday activities. Fever: temperature ≥ 38.0 C/100.4 F \nby any route (oral, axillary or tympanic); Grade 3 fever: > 39.0 C/102.2 F.\nGrade 3 headache, fatigue, myalgia, arthralgia: preventing normal activity Presentation by GSK at ACIP June 21, 2023Co-Ad Grade 3 FLU AREXVY\nCO-19\nModified Set: Solicited Systemic AEs Within 4 Days \nPost Vaccination\nGrade 3: >100 mm for erythema and swelling. Grade 3 pain: significant pain at rest; prevents normal everyday activities. \nFever: temperature ≥ 38.0 °C/100.4°F by any route (oral, axillary or tympanic); Grade 3 fever: > 39.0 °C/102.2°F.\n​Grade 3 headache, fatigue, myalgia, arthralgia: preventing normal activityRSV OA=ADJ -008: FLU QIV -HD\nPresentation by GSK at ACIP June 21, 202316.1%13.8%13.0%30.5%\n22.0% 23.5%\n2.1% 0.7% 2.0%24.3%\n17.1% 19.0%40.2%\n34.1%\n31.3%\n0.7% 0.7% 0.3% 0.9% 1.2% 0.5%0.2% 0.2% 0.5%1.9%0% 0.3%1.4% 1.4%0.3%\n020406080100\nCo-Ad\nVisit 1FLU\nVisit 1AREXVY\nVisit 2Co-Ad\nVisit 1FLU\nVisit 1AREXVY\nVisit 2Co-Ad\nVisit 1FLU\nVisit 1AREXVY\nVisit 2Co-Ad\nVisit 1FLU\nVisit 1AREXVY\nVisit 2Co-Ad\nVisit 1FLU\nVisit 1AREXVY\nVisit 2Arthralgia Fatigue Fever Headache MyalgiaSolicited Systemic Adverse Events\n% of \nParticipantsCo-Ad Grade 3 FLU AREXVY\nCO-20\nExposed Set: Solicited Systemic AEs Within 7 Days \nPost Vaccination\nGrade 3: >100 mm for erythema and swelling. Grade 3 pain: significant pain at rest; prevents normal everyday activities. \nFever: temperature ≥ 38.0 °C/100.4°F by any route (oral, axillary or tympanic); Grade 3 fever: > 39.0 °C/102.2°F.\n​Grade 3 headache, fatigue, myalgia, arthralgia: preventing normal activityRSV OA=ADJ -017: FLU aQIV\nPresentation by GSK at ACIP June 21, 202325.8%\n15.6% 17.1%45.7%\n28.7%29.9%\n2.1% 0.6% 1.1%32.2%\n19.5%23.7%39.0%\n23.0%31.9%\n0% 0% 0.2%0.2% 0.2% 0.2%0.2% 0% 0.2% 0% 0.2% 0% 0% 0.2% 0%\n020406080100\nCo-Ad\nVisit 1FLU\nVisit 1AREXVY\nVisit 2Co-Ad\nVisit 1FLU\nVisit 1AREXVY\nVisit 2Co-Ad\nVisit 1FLU\nVisit 1AREXVY\nVisit 2Co-Ad\nVisit 1FLU\nVisit 1AREXVY\nVisit 2Co-Ad\nVisit 1FLU\nVisit 1AREXVY\nVisit 2% of \nParticipantsArthralgia Fatigue Fever Headache MyalgiaSolicited Systemic Adverse EventsCo-Ad Grade 3 FLU AREXVY\nCO-21\nSummary of Findings\n1 dose of AREXVY provides durable efficacy against RSV -associated LRTD for 2 full RSV \nseasons, including against severe RSV disease, in adults with underlying comorbidities, and \nacross advancing ages\nRevaccination after 12 months does not appear to confer additional efficacy benefit for overall \npopulation; future data will inform optimal timing of revaccination\nReactogenicity and safety profiles of 2nddose in line with 1stdose; important for future \nrevaccination consideration\nAcross all studies no new cases of GBS, ADEM, or other neuroinflammatory demyelinating \ndisorders with additional exposure\nPresentation by GSK at ACIP June 21, 2023\nAREXVY can be administered with all types of commonly used influenza vaccines\n\nQA-22\nAReSVi -004 Phase 3 Trial Design1\n*Primary endpoints: NAb geometric mean titers (RSV -A and RSV -B) at Day 1 (pre -vaccination), D31, M6, and M12 post -dose 1; †CMI response in terms of frequency of \nRSVPreF3 -specific CD4+ and/or CD8+ T -cells expressing at least 2 activation markers. CD: cluster of differentiation; CMI: cell -mediated immune\n1. ClinicalTrials.gov. 2021. NCT04732871. https://clinicaltrials.gov/ct2/show/NCT04732871 (accessed May 2023)AReSVi -004 \nAREXVY: 1 initial dose, annual revaccination\nOlder adults\n≥ 60 years\nN=1653\nRandomized \n3:1:1\nAREXVY: 1 initial dose, revaccination M24\nAREXVY: 1 dose, no revaccination\nDay 1\n Month 12 Month 24\nPrimary objective: Evaluate humoral immune response following 1 -dose primary schedule up to 12 months post -dose 1*\nKey secondary objectives: Evaluate humoral and CMI† responses following 1 -dose primary schedule and revaccination \ndoses, up to study end (Month 36)\nSafety monitoring: Throughout studyR\nStudy initiated Feb 2021\nQA-23\nImmunogenicity Overview Through Month 18 Post Vaccination \nRSV-B Serum Neutralization Titers\n RSV-A Serum Neutralization Titers\n RSVPreF3 -specific CD4+ T -cells\nTimepoint (days)\nRSVPreF 3 CD4+ T -cells, /106cells (GM) GMT (ED60)\nGMT (ED60) \nTimepoint (days) Timepoint (days)020004000600080001000012000\n0 200 400 600**~10X\n**~3X~6X\n020004000600080001000012000\n0 200 400 600**~8.X\n**~2.4X**~4X\n05001000150020002500\n0 200 400 6001 dose 2 doses 1 dose 2 doses 1 dose 2 doses\nM6 M12 M18 D0 M6 M12 M18 D0 M6 M12 M18 D0**”~2 -4X* **2-3X\n**versus before vaccination 1; CD4+ T -cells expressing ≥2 activation markers including ≥1 cytokine among CD40L, 4 -1BB, IL -2, TNF -α, IFN-γ, IL-13, IL -17 (events/106\ncells; by intracellular staining). ED: Estimated Dilution; ED60: serum dilution inducing 60% inhibition in plaque -forming units; GMT: geometric mean titer; IL: \ninterleukin; TNF: tumor necrosis factorAReSVi -004 \n*RSV -A preliminary, final results pending", "summary": "CO-1 GSK’s RSVPreF3 OA Vaccine (AREXVY) AREXVY was approved by FDA on May 3, 2023, and is indicated for the prevention  of LRTD caused by RSV in adults 60 and older, as a single dose. ACIP June 21, 2023 Leonard Friedland, MD Vice President, Scientific Affairs and Public Health   Presentation by GSK at ACIP June 21, 2023  CO-2 Presentation Overview Efficacy and safety results over 2 full RSV seasons from pivotal Phase 3 Study ▪1 dose of AREXVY provides durable efficacy against RSV -associated…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/03-RSV-Adults-Friedland-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 23}
{"title": "04 RSV Adults Hutton 508", "content": "Economic Analysis of RSV \nVaccination in Older Adults \nDavid W. Hutton, PhD, MS\nAssociate Professor, Health Management and Policy, School of Public Health\nAssociate Professor of Global Public Health, School of Public Health\nAssociate Professor, Industrial and Operations Engineering, College of Engineering\nUniversity of Michigan\n\nResearch Team\nUniversity of Michigan\n•David Hutton, PhD\n•Lisa Prosser, PhD\n•Angela Rose, MPH\n•Kerra Mercon , MSCDC\n•Michael Melgar , MD\n•Mila Prill, MSPH\n•Jamison Pike, PhD\n•Ismael Ortega -Sanchez, PhD\n•Fiona Havers, MD\n•Michael Whitaker, MPH\n•Christopher Taylor, PhD\n•Amadea Britton, MD \n2\nConflicts of interest statements\n–No known conflict of interests.\n3\nMethods: Study question\n•Determine the cost -effectiveness of RSV vaccination by:\n•Evaluating the population burden of disease in the US \npopulation \n•Comparing vaccination to no vaccination using the incremental \ncost-effectiveness ratio\n•Scenario analyses exploring uncertainty.\n•Perspective: Societal\n•Major updates:\n•Update to base case incidence of RSV \n•Incorporation of season 2 efficacy of a single vaccine dose\n•Alignment of vaccine price with that assumed by manufacturers\n4\nMethods: Intervention(s)\n•Target population: US adults, stratified by age\n•Interventions: Pfizer and GSK vaccines\n•Each compared to No Vaccination\n•Base case assumes the age -based RSV vaccination \nrecommendation is for ages ≥65\n•Timeframe: 2 years\n•Analytic horizon: lifetime\n•Discounting rate: 3%\n5\nMethods: Decision Tree Model\nNo \nVaccination\nVaccinationInfection Hospitalization\nED\nNone of the aboveOutpatientAlive\nDeadInfection\nAdverse \nEventsSystemic Reaction\nInjection Site Reaction\nNone of the aboveSerious Adverse EventInfection Infection\n6\nMethods: Epidemiology\n•Incidence of RSV\n–Raw reported incidence may be underreported \nbecause of imperfect PCR sensitivity\n▪Base case assumption: 1.5x multiplier was applied to \ncrude incidence estimates\n▪Lower bound: lower multiplier assuming 95% PCR \nsensitivity (fewer missed cases)\n▪Higher bound: upper bound from base case assumption\n7For incidence of inpatient (RSV -NET), outpatient, and ED visits (McLaughlin et al. 2022), this applies the McLaughlin et al. mul tiplier of 1.5x to the crude \nincidence estimates.\n•McLaughlin JM, et al. Rates of Medically Attended RSV Among US Adults: A Systematic Review and Meta -analysis. Open Forum Infect Dis. 2022 Jun 17;9(7):ofac300. doi: \n10.1093/ ofid/ofac300. PMID: 35873302; PMCID: PMC9301578.\nOther studies speak directly to under -detection of RSV infection through use of upper respiratory PCR alone:\n•Onwuchekwa C, Moreo LM, Menon S, Machado B, Curcio D, Kalina W, Atwell JE, Gessner BD, Siapka M, Agarwal N, Rubbrecht M. Under -ascertainment of Respiratory Syncytial \nVirus infection in adults due to diagnostic testing limitations: A systematic literature review and meta -analysis. The Journal o f Infectious Diseases. 2023 Jan 20.\n•Ramirez J, Carrico R, Wilde A, Junkins A, Furmanek S, Chandler T, Schulz P, Hubler R, Peyrani P, Liu Q, Trivedi S. Diagnosis of Respiratory Syncytial Virus in Adults Substantially \nIncreases When Adding Sputum, Saliva, and Serology Testing to Nasopharyngeal Swab RT –PCR. Infectious Diseases and Therapy. 2023 May 6:1 -1.\nMethods: Epidemiology\nHospitalization\nVariable Value Range Source\nage 60 to <65 years 65.5 47.2 –101.3\nCDC RSV -NETage 65 to <70 years 93.8 65.9 –149.1\nage 70 to <75 years 118.7 85.5 –183.1\nage ≥75 years 302.9 212.6 –489\n•CDC RSV -NET data from RSV seasons: 2016 -17, 2017 -18, 2018 -19, and 2019 -2020.\n•Base value is based upon the average burden adjusted rate over those four seasons where \n“burden adjusted” means it is adjusted for 1.5x based on a reduced PCR test sensitivity * \n•Range lower bound is based upon the average burden adjusted rate over those four seasons, \nbut it uses a different “burden adjustment” multiplier of a \"Standard\" PCR test sensitivity of \n95%**.\n•Range upper bound is based on the upper 95% confidence limit for the base estimates\n* Kujawski SA, Whitaker M, Ritchey MD, Reingold AL, Chai SJ, Anderson EJ, Openo KP , Monroe M, Ryan P , Bye E, Como -Sabetti K, Bar ney GR, Muse A, Bennett NM, Felsen \nCB, Thomas A, Crawford C, Talbot HK, Schaffner W, Gerber SI, Langley GE, Kim L. Rates of respiratory syncytial virus (RSV) -assoc iated hospitalization among adults with \ncongestive heart failure -United States, 2015 -2017. PLoS One. 2022 Mar 9;17(3):e0264890. doi: 10.1371/journal.pone.0264890. PMID: 35263382; PMCID: PMC8906631.\n** McLaughlin JM, et al. Rates of Medically Attended RSV Among US Adults: A Systematic Review and Meta -analysis. Open Forum Infe ct Dis. 2022 Jun 17;9(7):ofac300. \ndoi: 10.1093/ ofid/ofac300. PMID: 35873302; PMCID: PMC9301578.8RSV incidence, per 100,000, Hospitalization\nMethods: Epidemiology\nED and Outpatient\nVariable Value Range Source\nRSV incidence, per 100,000 \nEmergency Department\nage 60 to <65 years 110.4 74 –132\nMcLaughlin 2022 age 65 to <74 years 200 133 –478\nage ≥75 years 200 133 –478\nRSV Incidence, per 100,000\nOutpatient\nage 60 to <65 years 1722 1148 –2041\nMcLaughlin 2022 age 65 to <74 years 2278 1519 –2893\nage ≥75 years 2278 1519 –2893\n9•McLaughlin et. al. is a Pfizer -sponsored meta -analysis\nMcLaughlin JM, Khan F, Begier E, Swerdlow DL, Jodar L, Falsey AR. Rates of Medically Attended RSV Among US Adults: A \nSystematic Review and Meta -analysis. Open forum infectious diseases 2022 Jul (Vol. 9, No. 7, p. ofac300). \nMethods: Incidence\nSeasonality\nSource: NREVSS (2015 -19)0%5%10%15%20%25%30%\nOct Nov Dec Jan Feb Mar Apr May Jun Jul Aug SepFraction of Annual Infections\n10\n0%10%20%30%40%50%60%70%80%90%100%\n0 2 4 6 810 12 14 16 18 20 22 24 26 28 30 32 34 36Efficacy\nMonth\nAgainst medically-attended RSV- LRTI/LRTD (hospitalization and ED)\nEst. Against medically-attended RSV- LRTI/LRTD (hospitalization and ED)\nAgainst medically-attended RSV-associated ARI (outpatient)\nEst. Against medically-attended RSV-associated ARI (outpatient)\n11Efficacy of a single vaccine dose  \nover time: Pfizer\nLinear decay to \n0% by 24 months84.6%\n65.2%75.0%\n55.0%\n0%10%20%30%40%50%60%70%80%90%100%\n0 2 4 6 8 10 12 14 16 18 20 22 24 26 28 30 32 34 36Efficacy\nMonth\nAgainst medically-attended RSV- LRTI/LRTD (hospitalization and ED)\nEst. Against medically-attended RSV- LRTI/LRTD (hospitalization and ED)\nAgainst medically-attended RSV-associated ARI (outpatient)\nEst. Against medically-attended RSV-associated ARI (outpatient)87.5%\n52.9%79.0%\n27.8%Linear decay to \n0% by 24 months\n12Efficacy of a single vaccine dose  \nover time: GSK\nUpper and Lower Bound Efficacy \nDuration Scenarios\n13GSK Pfizer\n0%20%40%60%80%100%\n0 20 40Efficacy\nMonthAgainst medically-attended \nRSV- LRTI/LRTD \n(hospitalization and ED)\nBase Shorter Longer0%20%40%60%80%100%\n0 20 40Efficacy\nMonthAgainst medically-attended \nRSV- LRTI/LRTD \n(hospitalization and ED)\nBase Shorter Longer\nMethods: RSV Medical Costs\nVariable Value Range Source\nDisease -specific \nhospitalization costs (per \nhospitalization)\nage 60 to <65 years $21,417 9,288 –45,454\nAckerson 2020* age 65 to <75 years $21,417 10,491 –43,619\nage ≥75 years $22,425 10,491 –43,619\nDisease -specific ED costs \n(per ED visit)\nage 60 to <65 years $1,210 -\n2016 Marketscan* age 65 to <75 years $1,210 -\nage ≥75 years $1,210 -\nDisease -specific \noutpatient costs (per \noutpatient visit)\nage 60 to <65 years $117.58 65.88 -145.38 MarketScan\nand Medicare FFS, 2020 -\n2021age 65 to <75 years $100.86 50.48 -120.08\nage ≥75 years $100.86 50.48 -120.08\n*Updated to Q3 2022$ using GDP Deflator14\nMethods: Additional Inputs\n•Also included \n–RSV mortality\n–RSV QALYs lost\n–RSV illness productivity costs\n–Vaccination healthcare and productivity costs\n–Vaccination adverse events\n•Systemic reactions\n•Injection site reactions\n•Serious adverse events\n•Medical costs\n•Productivity costs\n•These assumption remain unchanged from \nFebruary\n15\nMethods: Sensitivity analyses\n•Sensitivity analyses conducted\n–One-Way and Two -Way\n–Age-based recommendation for RSV vaccination\n•age ≥65 years\n•age 60 to <65 years\n–Vaccine cost\n▪$180 -$340\n•Scenario analysis: shorter and longer duration of \nefficacy\n16\nResults: Base Case\n•Cohort of US adult population age 65+ as \nof 2020 Census\n•Vaccine Cost:\n–Pfizer: $200\n–GSK: $270\n•Two Year Timeframe\n17\nNumber Needed to Vaccinate, \nPfizer\n18\nTwo Year Timeframe\n52 \n617 \n1,040 \n5,201 \n26,671 \n173 \n1,734 40 \n340 \n401 \n2,007 \n7,842 \n67 \n669 \n - 5,000 10,000 15,000 20,000 25,000 30,000Number Needed to Vaccinate\n Age 60-64 age ≥65 years \nNet Cost per Outcome Averted, \nPfizer\n19Two Year Timeframe\nAge-based vaccination recommendation: ≥65 years\nPfizer vaccine cost: $200Outpatient ED Hospitalizations ICU Stays Deaths\n≥65 years $5,600 $48,000 $57,000 $280,000 $1,100,000 \n60 to <65 $9,400 $110,000 $190,000 $930,000 $4,800,000 \nNumber Needed to Vaccinate, \nGSK\n20Two Year Timeframe\n57 \n669 \n1,128 \n5,639 \n28,919 \n188 \n1,880 43 \n369 \n435 \n2,176 \n8,503 \n73 \n725 \n - 5,000 10,000 15,000 20,000 25,000 30,000 35,000Number Needed to Vaccinate\n age 60 to <65 years age ≥65 years \nNet Cost per Outcome Averted, \nGSK\n21Two Year Timeframe\nAge-based vaccination recommendation: ≥65 years\nGSK vaccine cost: $270Outpatient ED Hospitalizations ICU Stays Deaths\n≥65 years $9,300 $80,000 $94,000 $470,000 $1,800,000 \n60 to <65 $14,000 $170,000 $290,000 $1,400,000 $7,300,000 \nSummary measure(s)\nPfizer\nAge-based vaccination \nrecommendation: ≥65 years ICER ($/QALY) ICER ($/LY)\n94,673 112,806\n22QALY = Quality -Adjusted Life -Year\nICER = Incremental Cost -Effectiveness Ratio\nLY = Life -Year\nICER values do not depend on cohort size or uptake\n$200 vaccine cost\nTwo Year Timeframe Age-based vaccination \nrecommendation: 60 to <65\nyears ICER ($/QALY) ICER ($/LY)\n218,350 313,379\nSummary measure(s)\nGSK\nAge-based vaccination \nrecommendation: ≥65 years ICER ($/QALY) ICER ($/LY)\n167,301 187,853\n23QALY = Quality -Adjusted Life -Year\nICER = Incremental Cost -Effectiveness Ratio\nLY = Life -Year\nICER values do not depend on cohort size or uptake\n$270 vaccine cost\nTwo Year Timeframe Age-based vaccination \nrecommendation: 60 to <65\nyears ICER ($/QALY) ICER ($/LY)\n372,656 478,947\nResults: Sensitivity analyses, \n•Tornado Diagrams \n–one parameter varied at a time\n•Age and Vaccine Cost\n•Vaccine Duration\n24\nSensitivity analyses, Pfizer \nTornado Diagram\n25$200 vaccine cost\nTwo Year Timeframe\nAge-based vaccination recommendation: ≥65 years, VE=Vaccine Efficacy LRTD= Lower Respiratory \nTract Disease, S1=Season 1, S2=Season 2.$0 $50,000 $100,000 $150,000 $200,000\nVaccine Cost\nVE against hospitalization and ED S2\nIncidence of RSV hospitalization\nVE against hospitalization and ED S1\nCost per Hospitalization\nOutpatient QALYs Lost, Adult\nIncidence of outpatient visits for RSV\nMortality, adults hospitalized with RSV\nVE against oupatient illness S2\nED IncidenceICERAge ≥65\nLow Assumption High Assumption\nSensitivity analyses, GSK \nTornado Diagram\n26$270vaccine cost\nTwo Year Timeframe\nAge-based vaccination recommendation: ≥65 years, VE= Vaccine Efficacy, LRTD= Lower Respiratory \nTract Disease, S1=Season 1, S2=Season 2.$0 $50,000 $100,000 $150,000 $200,000 $250,000 $300,000\nIncidence of RSV hospitalization\nVE against hospitalization and ED S2\nVaccine Cost\nOutpatient QALYs Lost, Adult\nCost per Hospitalization\nVE against hospitalization and ED S1\nIncidence of outpatient visits for RSV\nMortality, adults hospitalized with RSV\nVE against oupatient illness S2\nED IncidenceICERAge ≥65\nLow Assumption High Assumption\n $- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000 $450,000 $500,000\n $150  $175  $200  $225  $250  $275  $300  $325  $350ICER\nVaccine Cost\nAge 60-64 age ≥65 yearsSensitivity analysis: Vaccine \nCost, Pfizer\n27Two Year Timeframe\n $- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000 $450,000 $500,000\n $150  $175  $200  $225  $250  $275  $300  $325  $350ICER\nVaccine Cost\nAge 60-64 age ≥65 yearsSensitivity analysis: Vaccine \nCost, GSK \n28Two Year Timeframe\n0%20%40%60%80%100%\n0 20 40Efficacy\nMonthAgainst medically-attended RSV-\nLRTI/LRTD (hospitalization and ED)\nBase Shorter Longer0%20%40%60%80%100%\n0 20 40Efficacy\nMonthAgainst medically-attended RSV-\nLRTI/LRTD (hospitalization and ED)\nBase Shorter LongerPfizer GSKVaccine Efficacy Duration \nScenarios\n29\nSensitivity analyses, Pfizer: \nVarying Duration of Efficacy\n $- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000 $450,000 $500,000\n $150  $175  $200  $225  $250  $275  $300  $325  $350ICER\nVaccine Cost\nPfizer Base age ≥65 years\nPfizer Zero Efficacy after 14 months age ≥65 years\nPfizer Zero Efficacy after 36 months age ≥65 years\n30Age-based vaccination recommendation: ≥65 years\nSensitivity analyses, GSK: \nVarying Duration of Efficacy\n $- $50,000 $100,000 $150,000 $200,000 $250,000 $300,000 $350,000 $400,000 $450,000 $500,000\n $150  $175  $200  $225  $250  $275  $300  $325  $350ICER\nVaccine Cost\nGSK Base age ≥65 years\nGSK Zero Efficacy after 18 months age ≥65 years\nGSK Zero Efficacy after 36 months age ≥65 years\n31Age-based vaccination recommendation: ≥65 years\nLimitations\n•Model Structure\n–No risk groups\n–No dynamic transmission. No impact of the vaccine \non transmission and indirect effects\n•Uncertain inputs\n–Vaccine cost \n–RSV Incidence\n–Long -term efficacy \n32\nSummary\n•Vaccination potentially Cost -Effective\n•Results vary based on:\n–Vaccine Cost\n•ICER: 80,000 –220,000 $/QALY\n–Incidence of RSV Hospitalization\n•$50,000 -230,000 $/QALY\n–Vaccine Efficacy\n•ICER: ~80,000 -270,000 $/QALY\n–Ages Vaccinated\n•ICER: ~50,000 -370,000 $/QALY\n–Duration of Efficacy\n•ICER: ~80,000 -170,000 $/QALY33\nThank You\n•Please send comments to:\n•dwhutton@umich.edu\n34", "summary": "Economic Analysis of RSV  Vaccination in Older Adults  David W. Hutton, PhD, MS Associate Professor, Health Management and Policy, School of Public Health Associate Professor of Global Public Health, School of Public Health Associate Professor, Industrial and Operations Engineering, College of Engineering University of Michigan  Research Team University of Michigan •David Hutton, PhD •Lisa Prosser, PhD •Angela Rose, MPH •Kerra Mercon , MSCDC •Michael Melgar , MD •Mila Prill, MSPH •Jamison…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/04-RSV-Adults-Hutton-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 34}
{"title": "05 RSV Adults Ortega Sanchez 508", "content": "Economics of Vaccinating U.S. Adults ≥60 \nyears -old against \nRespiratory Syncytial Virus\nUPDATED SUMMARY COMPARING MODELS FROM:\nGSK,Pfizer AND University of Michigan -CDC\nIsmael R. Ortega -Sanchez, PhD\nNCIRD/CDC\nACIP Meeting, June 21, 2023\n1Disclaimer : The findings and conclusions in this report are those of the authors and do not necessarily represent the views of \nthe Centers for Disease Control and Prevention. \nNational Center for Immunization & Respiratory Diseases\nConflict of interest\n•GSK model : Daniel Molnar et al.,  [complete list and affiliations, upon request]\n•GSK manufactures the adjuvanted RSVPreF3 vaccine \n•RTI Health Solutions was funded by GSK\n•Pfizer model : Derek Weycker et al., [complete list and affiliations, upon request]\n•Pfizer manufacturers the bivalent RSVpreF vaccine\n•Policy Analysis Inc. was funded by Pfizer\n•UM-CDC model : David W Hutton et al. from Univ Michigan, …, Ismael R Ortega -\nSanchez et al. from CDC [complete list and affiliations, upon request ]\n•All authors: No conflicts of interest\n2\nEconomic analysis\nPolicy questions: Should adults  ≥65 years of age (or ≥60 years of age) receive \none dose of Respiratory Syncytial Virus (RSV) vaccine (GSK or Pfizer product) for \nthe prevention of RSV disease and its complications?\nQuestion : Is vaccinating adults aged ≥65 years (or ≥60 years) against RSV cost-\neffective ?\nComparator Intervention\nBase -case scenario: What is the incremental cost-effectiveness of vaccinating adults aged \n≥65 years (or ≥60 years) using RSV vaccine relative to “No vaccination”?\n3Unvaccinated \n≥65yr -olds\n(or ≥60yr -olds)Vaccinating\n≥65yr -olds\n(or ≥60yr -olds)\nFocus on key features for model comparison\n•Modeling approach\n•Targeted population(s)\n•Perspective (healthcare vs. societal)\n•Intervention strategy and comparator\n•Inputs for RSV disease burden, vaccine efficacy, and costs\n•Incidence of RSV disease, rates of outcomes\n•Direct and indirect costs of RSV disease\n•Intervention: Vaccine efficacy , duration of protection , safety and program \ncosts\n•Assumptions\n•Strong, influential assumptions\n4Note : For this and all slides, to specifically identify changes and updates from those presented last February 2023, the text wil l \nappear either highlighted, marked in red or with the word updated at the top of the slide or table.\n5Modeling design and assumptions\nGSK Pfizer UM-CDC\nStatic analytical decision -making models ✔ ✔ ✔\nSensitivity analyses (and probabilistic simulation)✔(✔)✔(✔)✔\nHypothetical population ≥65yrs -old (and ≥60 -yrs-old) ✔(✔)✔(✔)✔(✔)\nTime Frame: at least 2 yr. after a dose of RSV vaccine✔ ✔ ✔\nAnalytic Horizon: Age -specific Life Expectancy✔ ✔ ✔\nDiscount rate: 3% ✔ ✔ ✔\nYear of economic outcomes measured: 2022 ✔ ✔ ✔\nSocietal perspective (and healthcare perspective)✔(✔)✔(✔)✔(✔)\n6Inputs and main outcomes\nPrevention of:\n•Outpatient visits for RSV\n•RSV hospitalizations\n•RSV-associated deaths\nQALYs saved\n$/QALY saved\nNumber needed to\nvaccinate (NNV) to avert an: \n•Outpatient visit for RSV\n•RSV hospitalization\n•RSV-associated death\nGSK\nUpdatedPfizer\nUpdatedUM-CDC\nUpdated\n✔ ✔ ✔\n✔ ✔ ✔\n✔ ✔ ✔\n✔ ✔ ✔\n✔ ✔ ✔\n✔ ✔ ✔\n✔ ✔ ✔\n✔ ✔ ✔\nHCRU = health care resource use\nGSK, Pfizer and UM-CDC models comparison: \nSelected outcome ratios for RSV vaccines (Feb 2023)\n7UM-CDC \nmodel\nVac Price \n$100GSK \nmodel\nVac Price \n$148\n$ / QALY gained\nVaccinating adults ≥65 yrs. 180,720 68,489\nVaccinating adults ≥60 yrs. 229,895 78,971\n$ / hospitalization averted\nVaccinating  adults ≥65 yrs. 101,406 57,114\nVaccinating adults ≥60 yrs. 133,992 69,638GSK vaccine\nUM-CDC \nmodel\nVac Price \n$100Pfizer\nmodel\nVac Price \n$200\n$ / QALY gained\nVaccinating adults ≥65 yrs. 189,407 43,749\nVaccinating adults ≥60 yrs. 233,779 50,197\n$ / hospitalization averted\nVaccinating  adults ≥65 yrs. 122,886 19,845\nVaccinating adults ≥60 yrs. 161,310 23,271Pfizer vaccine\nGSK, Pfizer and UM-CDC models comparison: \nSelected outcome ratios for RSV vaccines (June 2023)\n8UM-CDC \nmodel\nVac Price \n$270GSK \nmodel\nVac Price\n$270\n$ / QALY gained\nVaccinating adults ≥65 yrs. 167,301 55,088\nVaccinating adults ≥60 yrs. 205,638 64,348\n$ / hospitalization averted\nVaccinating adults ≥65 yrs. 94,375 43,456\nVaccinating adults ≥60 yrs. 120,056 53,644GSK vaccine\nUM-CDC \nmodel\nVac Price \n$200Pfizer\nmodel\nVac Price \n$200\n$ / QALY gained\nVaccinating adults ≥65 yrs. 94,673 19,585\nVaccinating adults ≥60 yrs. 118,735 23,921\n$ / hospitalization averted\nVaccinating  adults ≥65 yrs. 56,571 8,797\nVaccinating adults ≥60 yrs. 75,382 10,982Pfizer vaccine\n$50 $100 $150 $200\nVaccine Cost\nVE against hospitalization and ED S2\nIncidence of RSV hospitalization\nVE against hospitalization and ED S1\nCost per Hospitalization\nOutpatient QALYs Lost, Adult\nIncidence of outpatient visits for RSV\nMortality, adults hospitalized with RSV\nVE against oupatient illness S2\nED Incidence\nLow Assumption High Assumption\n$50 $100 $150 $200 $250 $300\nIncidence of RSV hospitalization\nVE against hospitalization and ED S2\nVaccine Cost\nOutpatient QALYs Lost, Adult\nCost per Hospitalization\nVE against hospitalization and ED S1\nIncidence of outpatient visits for RSV\nMortality, adults hospitalized with RSV\nVE against oupatient illness S2\nED IncidenceGSK: $/QALY gained (thousands)\nLow Assumption High AssumptionUM-CDC model : Updated One-way Sensitivity Analyses\nBase case: Age ≥65yrs; $1 67,301/QALY (GSK), $94,673/QALY (Pfizer)\n9Vaccine cost per dose $270/dose (GSK) , $200/dose (Pfizer)\nTwo-year time frame\nAge-based vaccination recommendation: ≥65 years, VE=Vaccine Efficacy LRTD= Lower Respiratory Tract Disease, S1=Season 1, S2=Seas on 2.\nGSK model : Updated One-way Sensitivity Analyses\nBase case: Age ≥60 years; $ 64,348 /QALY saved*\n10* GSK base -case vaccine price = $270/dose, three -year time frame\nAverage annual incidence of first RSV ARI event\nPercentage of RSV LRTD cases resulting in hospitalization\nEfficacy against RSV LRTD: Waning rates first vaccination with RSVPreF3 vaccine <36 months\nRSVPreF3 vaccine: Peak % efficacy after first vaccination against RSV LRTD caused by first RSV infection\nProbability of death given RSV LRTD\nVaccination costs per administered dose with RSVPreF3 vaccine -Purchase cost per dose –Cost\nProportion RSV LRTD within first RSV ARI event\nBaseline QALYs -General population\nEfficacy against RSV ARI: Waning rates first vaccination with RSVPreF3 vaccine <36 months\nRSVPreF3 vaccine: Peak % efficacy after first vaccination against first RSV ARI event\nDirect cost per RSV LRTD event @ 1stinfection -Unvaccinated\n\nPfizer model : Updated One-way Sensitivity Analyses\nBase case: Age≥60 years: $23,921/QALY saved*\n11Base case\n* Pfizer base -case vaccine price = $200/dose,  RSV -H= RSV -associated hospitalization\nGSK, Pfizer and UM-CDC models comparison: \nSelected inputs \n12•RSV-hospitalization rate\nGSK: Proportion of medically attended RSV hospitalized cases identified by PCR, differentiated by age \n(Belongia, 2018)\nPfizer : Differentiated by age and comorbidity profile (Pfizer data on file)\nCDC: Differentiated by age (four RSV seasons in CDC RSV -NET data )\n•Initial VE & waning over time: (updated data from GSK’s & Pfizer’s phase 3)\nGSK: VE peaks in month 2, wanes linearly, reaching 0% at 34 or 43mos (depending on outcome)\nPfizer: VE is flat 7mos, wanes linearly thereafter, reaches 0% at 24mos\nCDC: Step -wise: VE flat 7mos, partial drop & flat 7 -14mos ( Pfizer), 7 -18mos (GSK), reaches 0% at 24mos\n•Unitary medical cost of RSV outcomes\nGSK: Age -& outcome specific cost for symptomatic RSV LRTD & URTI cases (medically attended and \nnon-medically attended) (data from Centers for Medicare and Medicaid Services)\nPfizer: Age-, outcome -& comorbidity -specific cost for medically attended RSV illness\nCDC: Age -& outcome -specific cost for medically attended RSV illness\nARI = acute respiratory infection\nLRTD = lower respiratory tract disease\nURTI = upper respiratory tract illness \n13UM-CDC GSK Pfizer\nIncidence of RSV outpatient illness \n(per 100,000 persons per year)2,278\n(base -case for adults ≥65 years)a1,348\n(for adults ≥65 years)b2,430\n(base case for adults \n≥65 years)c\nIncidence of RSV hospitalization \n(per 100,000 persons per year)162\n(base -case for adults ≥65 years)d256.3\n(for adults ≥65 years)b,e300\n(base -case for adults \n≥65 years)c\nDirect medical costs per RSV \nhospitalization$21,417 –$22,425\n(age -dependent)f$13,112 –$26,224\n(age -dependent)g,h$12,048 –$38,380\n(age -and comorbidity -\ndependent)h,i\na McLaughlin et al. Open Forum Infect Dis (2022): https://doi.org/10.1093/ofid/ofac300\nb Adapted from Belongia et al. Open Forum Infect Dis (2018): https://doi.org/10.1093/ofid/ofy316\nc Adapted from McLaughlin et al. Open Forum Infect Dis (2022): https://doi.org/10.1093/ofid/ofac300 ; Ramirez et al. Infect Dis Ther (2023): https://doi.org/10.1007/s40121 -023-00805 -1\nd RSV-NET, CDC unpublished data. Age -specific hospitalization rate per 100,000: 65.5 (60 to <65yrs), 93.8 (65 to <70yrs), 118.7 (7 0 to <75yrs) and 302.9 (75+yrs). Crude surveillance rates were \nupwardly adjusted 1.5x due to incomplete case detection from reliance on upper respiratory RT -PCR (McLaughlin et al. Open Forum Infect Dis (2022): https://doi.org/10.1093/ofid/ofac300\ne Adapted from Falsey et al. NEJM (2005): https://doi.org/10.1056/nejmoa043951 ; Herring et al. Vaccine (2022): https://doi.org/10.1016/j.vaccine.2021.12.002\nf Ackerson et al. J Infect Dis (2020). Updated to Q3 2022$ using GDP Deflator: https://doi.org/10.1093/infdis/jiaa183 ; Branche et al. Clin Infect Dis (2022): https://doi.org/10.1093/cid/ciab595\ng CMS Medicare Inpatient Hospitals (DRG Average Payments from 2019 dataset)\nh Kaiser Family Foundation (How much more than Medicare do private insurers pay? 2020): https://www.kff.org/medicare/issue -brief/how -much -more -than -medicare -do-private -insurers -\npay-a-review -of-the-literature/\ni Merative MarketScan Commercial Claims and Encounters (CCAE) and Medicare Supplemental Coordination of Benefits (MDCR) Databases (2016 -2019)GSK, Pfizer and UM-CDC models: Key differences in \nmodel inputs \nUM-CDC model : Sensitivity of Cost per QALY saved to RSV -Related \nHospitalization Rates among Adults ≥65 years: 2-year timeframe\n14Base case for Pfizer and GSK are shown with blue and orange solid filled diamond markers, respectively : Estimated using the adjusted mean RSV -related hospitalization rate over RSV seasons: 2015 -16, \n2016 -17, 2017 -18, and 2018 -19. Adjusted rate for lower sensitivity of PCR testing. CDC RSVnet\nBlue ball markers : Estimated usin g Pfizer vaccine VE and price input data for the specific hospitalization rate as reported by the reference . \nOrange ball markers : Estimated usin g GSK vaccine VE and price input data for the specific hospitalization rate as reported by the reference .\nLabels in markers: They refer to the specific source of the RSV -associated hospitalization rate used in the estimation of either vaccine cost per QALY saved. Parentheses include either the year of the \npublication or the place where the data for the study was collected.  Pfizer BasePfizer Branche (Rochester)\nPfizer Branche (NYC)\nPfizer Belongia\nPfizer Widmer (2012)Pfizer Widmer (2014)GSK BaseGSK Branche (Rochester)\nGSK Branche (NYC)\nGSK Belongia\nGSK Widmer (2012)GSK Widmer (2014)\n $- $40,000 $80,000 $120,000 $160,000 $200,000 $240,000\n -  50  100  150  200  250  300Incremental cost per QALY gained\nRSV-related hospitalization rate per 100,000\nUM-CDC model : Sensitivity of Cost per QALY saved to RSV -Related \nHospitalization Rates among Adults ≥65 years: 2-year timeframe\n15Pfizer BasePfizer Branche (Rochester)\nPfizer Branche (NYC)\nPfizer Belongia\nPfizer Widmer (2012)Pfizer Widmer (2014)GSK BaseGSK Branche (Rochester)\nGSK Branche (NYC)\nGSK Belongia\nGSK Widmer (2012)GSK Widmer (2014)\n $- $40,000 $80,000 $120,000 $160,000 $200,000 $240,000\n -  50  100  150  200  250  300Incremental cost per QALY gained\nRSV-related hospitalization rate per 100,000\nBase case for Pfizer and GSK are shown with blue and orange solid filled diamond markers, respectively : Estimated using the adjusted mean RSV -related hospitalization rate over RSV seasons: 2015 -16, \n2016 -17, 2017 -18, and 2018 -19. Adjusted rate for lower sensitivity of PCR testing. CDC RSVnet\nBlue ball markers : Estimated usin g Pfizer vaccine VE and price input data for the specific hospitalization rate as reported by the reference . \nOrange ball markers : Estimated usin g GSK vaccine VE and price input data for the specific hospitalization rate as reported by the reference .\nLabels in markers: They refer to the specific source of the RSV -associated hospitalization rate used in the estimation of either vaccine cost per QALY saved. Parentheses include either the year of the \npublication or the place where the data for the study was collected.  \nUM-CDC model : Sensitivity of Cost per QALY saved to RSV -Related \nHospitalization Rates among Adults ≥65 years: 2-year timeframe\n16Pfizer BasePfizer Branche (Rochester)\nPfizer Branche (NYC)\nPfizer Belongia\nPfizer Widmer (2012)Pfizer Widmer (2014)GSK BaseGSK Branche (Rochester)\nGSK Branche (NYC)\nGSK Belongia\nGSK Widmer (2012)GSK Widmer (2014)\n $- $40,000 $80,000 $120,000 $160,000 $200,000 $240,000\n -  50  100  150  200  250  300Incremental cost per QALY gained\nRSV-related hospitalization rate per 100,000$55.1K, GSK (3-yr TF)\n$19.6K, Pfizer\nBase case for Pfizer and GSK are shown with blue and orange solid filled diamond markers, respectively : Estimated using the adjusted mean RSV -related hospitalization rate over RSV seasons: 2015 -16, \n2016 -17, 2017 -18, and 2018 -19. Adjusted rate for lower sensitivity of PCR testing. CDC RSVnet\nBlue ball markers : Estimated usin g Pfizer vaccine VE and price input data for the specific hospitalization rate as reported by the reference . \nOrange ball markers : Estimated usin g GSK vaccine VE and price input data for the specific hospitalization rate as reported by the reference .\nLabels in markers: They refer to the specific source of the RSV -associated hospitalization rate used in the estimation of either vaccine cost per QALY saved. Parentheses include either the year of the \npublication or the place where the data for the study was collected.  \nUM-CDC model : Sensitivity of Cost per QALY saved to RSV -Related \nHospitalization Rates among Adults ≥65 years: 2-year timeframe\n17Pfizer BasePfizer Branche (Rochester)\nPfizer Branche (NYC)\nPfizer Belongia\nPfizer Widmer (2012)Pfizer Widmer (2014)GSK BaseGSK Branche (Rochester)\nGSK Branche (NYC)\nGSK Belongia\nGSK Widmer (2012)GSK Widmer (2014)\n $- $40,000 $80,000 $120,000 $160,000 $200,000 $240,000\n -  50  100  150  200  250  300Incremental cost per QALY gained\nRSV-related hospitalization rate per 100,000$70.1K, GSK (2-yr TF)\n$19.6K, Pfizer\nBase case for Pfizer and GSK are shown with blue and orange solid filled diamond markers, respectively : Estimated using the adjusted mean RSV -related hospitalization rate over RSV seasons: 2015 -16, \n2016 -17, 2017 -18, and 2018 -19. Adjusted rate for lower sensitivity of PCR testing. CDC RSVnet\nBlue ball markers : Estimated usin g Pfizer vaccine VE and price input data for the specific hospitalization rate as reported by the reference . \nOrange ball markers : Estimated usin g GSK vaccine VE and price input data for the specific hospitalization rate as reported by the reference .\nLabels in markers: They refer to the specific source of the RSV -associated hospitalization rate used in the estimation of either vaccine cost per QALY saved. Parentheses include either the year of the \npublication or the place where the data for the study was collected.  \nGSK, Pfizer and UM-CDC:  Initial or Early Peak of \nVaccine Efficacy & Decline in Season 2 ( updated )\n18a VE over median (GSK) or mean (Pfizer) 7 months for season 1, VE through a median 18 months (GSK) or 14 months (Pfizer) for season 2 as reported in the follow up in phase 3 clinical trials\nb Manufacturer phase 3 trial data; VE against medically attended acute respiratory illness\nc GSK phase 3 trial data; VE against acute respiratory illness, regardless of whether medically attended. Reported peak value atmonth 2.\nd GSK phase 3 trial data; VE against medically attended lower respiratory tract disease\ne Pfizer phase 3 trial data; VE against medically attended lower respiratory tract illness with ≥3 lower respiratory symptoms\nf GSK phase 3 trial data; VE against lower respiratory tract disease, regardless of whether medically attended. Reported peak value at month 2.UM-CDC Model GSK Model Pfizer Model\nGSK vaccine Pfizer vaccine GSK vaccine Pfizer vaccine\nVaccine efficacy (VE) against RSV \noutpatient illnessa Season 179.0\n(54.3 –91.5)b65.2\n(36.0 –82.0)bSeason 1 Peak: 74.2\n(56.4 –94.0)\nWeighted linear regression \nover time of estimated \nefficacy from clinical trialc65.1\n(35.9 –82.0)b\nSeason 227.8\n(0 –60.4)b55.0\n(0 –82.0)b55.0\n(95% CI: -3.4–82.0)b\nVE against RSV hospitalization and \nemergency department visitaSeason 187.5\n(58.9 –97.6 )d84.6\n(32.0 –98.3)eSeason 1 Peak: 88.0\n(65.8 –99.2)\nWeighted linear regression \nover time of estimated \nefficacy from clinical trialf84.6\n(32.0 –98.3)e\nSeason 252.9\n(0 –81.2)d75.0\n(0 –97.4)e75.0\n(95% CI: -25.3 –97.4)e\nGSK, Pfizer and UM-CDC: Assumption on waning of \nvaccine efficacy (VE) per outcome ( Feb 2023 )\n19GSKVE peaks at 2 months then wanes per month         \nRSV-ARI = 5.36% points per month (range: 0.00 -\n13.37%)      \nRSV-LRTD = 2.63% points per month (range: 0.00 -\n10.95%)\nNo residual protection after 12 monthsPfizerInitial VE assumed to persist for 7 months, \nThen to decline linearly to 0% effectiveness at 24 \nmonths\nResidual though declining protection up to 24 \nmonthsUM-CDCVaccine and outcome -specific\nFor both vaccines:\nExponential decay up to 12 months \nand then 0% afterwards; calibrated such that the \nfirst 6 months VE equals the trial estimate\n\nGSK, Pfizer and UM-CDC: Assumption on waning of \nvaccine efficacy (VE) per vaccine & outcome ( June 2023 )\n20\nGSK\nUM-CDC UM-CDC\nThe pink -shaded areas denote a higher level of uncertainty of the waning assumption beyond available phase 3 data\nFeb 2023GSK: Residual Vaccine Effectiveness (Feb 2023 \nACIP) and updated analyses ( June 2023 )\n21RSV LRTD : 50% of peak VE ( 88% ) \nassumed in month 1, peak VE \ndeclines by 2.10% (2.63% in Feb) \nmonthly rate beginning in month 2 \nthough 20-month maximum follow \nup of trial .  Assumed to follow \nlinear decline trend afterwards. \nReaches 0% in month 43 \nRSV ARI : 50% of peak VE ( 74% ) \nassumed in month 1, peak VE \ndeclines by 2.26% (5.36% in Feb) \nmonthly rate beginning in month 2 \nthough 20-month maximum follow \nup of trial .  Assumed to follow \nlinear decline trend afterwards. \nReaches 0% in month 34 \nThe pink -shaded area denotes a higher level of uncertainty of the waning assumption beyond \navailable phase 3 data\nPfizer : Residual Vaccine Effectiveness (Feb \n2023 ACIP) and updated analyses ( June 2023 )\n22\nHospitalization or ED : Initial \nVE (84.6%) assumed to \npersist for 7 months, to \ndecline to 75% at 14 months, \nand then decline to 0% at  \n24thmonth \nOutpatient : Initial VE ( 65.1% ) \nassumed to persist for 7 \nmonths, to decline to 55% at \n14 months, and then decline \nto 0% at  24thmonth \nThe pink -shaded area denotes a higher level of uncertainty of the waning assumption beyond \navailable phase 3 data\nUM-CDC: Updated assumption on waning of \nvaccine efficacy per vaccine and outcome \n23Hospitalization or ED: Initial VE (87.5% \nGSK; 84.6% Pfizer ) assumed to persist \nfor 7 months, to drop to 52.9% ( GSK), \n75%( Pfizer) and remain flat from \nmonth 8 to month 18 ( GSK) or month \n14 (Pfizer ), and then decline linearly to \n0% at month 24.\nMedically attended (Outpatient): \nInitial VE (79% GSK; 65.2% Pfizer ) \nassumed to persist for 7 months, to \ndrop to 27.8% ( GSK), 55%( Pfizer ) and \nremain flat from month 8 to month 18 \n(GSK), month 14 ( Pfizer ), and then \ndecline linearly to 0% at month 24 \nGSK\nPfizer87.5%\n52.9%79.0%\n27.8%\n84.6%\n75.0%\n65.2%\n55.0%\nThe pink rectangle highlights the difference in duration of protection assumption between vaccines \nComparison of GSK and Pfizer vaccines: Update base \ncase & scenario $/QALY results using UM-CDC model\n24aIncidence rates: Lower incidence assumes 95% RT -PCR test sensitivity, Higher rate incorporates the upper limit of the 95% CI ar ound the base case incidence rate \nestimate.\nb Recommendation = vaccination at age ≥65 years; incidence rates of RSV outcomes upwardly adjust 1.5x to account for incomple te RT-PCR sensitivity on a \nrespiratory specimen (McLaughlin et al; Open Forum Infect Dis 2022); vaccine efficacy only considered for two years post -vaccina tionScenario GSK Pfizer\nVaccinating adults aged 60 to <65 years only $372,656 $218,250\nLower incidence of RSVain adults ≥65 years $276,393 $161,487\nVaccine cost $340 per dose $220,864 $187,865\nVaccinating adults ≥60 years, $205,638 $118,735\nResidual vaccine protection = 0% at 18 (GSK) or 14 (Pfizer) months $170,022 $135,886\nBase caseb(Vacc price $270 GSK, $200 Pfizer , adults ≥65yrs) $167,301 $94,673\nVaccine cost $180 per dose $98,485 $81,358\nHigher incidence of RSVbin adults ≥65 years $84,736 $40,467\nLimitations\n25•Factors not considered that may result in overestimating the ICER \n(underestimating the cost -effectiveness) of RSV vaccination\n•All of the 3 models assumed no indirect effects of vaccination (i.e., no protection against RSV \ntransmission)\nExcept UM-CDC model\n•Manufacturers models do not include RSV -related medical costs incurred after discharge \nfrom an RSV -associated hospitalization or emergency department visit: \n•Stay in long -term care or rehabilitation facility\n•Manufacturers models do not include potential vaccine -associated serious \nadverse events (SAEs)\n•Quality of life impact, resource utilization and costs associated with hypothetical SAEs \n•Vaccine efficacy beyond clinical trial follow -up time (beyond 14 months, Pfizer\nor 18 months, GSK) is unknown\n•All 3 models assumed non -zero declining efficacy beyond 14 or18 months \nConclusion\n26•Differences in key inputs among GSK, Pfizer and UM-CDC models explain differences in results:\n•Annual incidence of RSV hospitalization and outpatient disease\n•Initial vaccine (season 1) and waning of protection (VE season 2+)\n•Selection of medical costs sources and data extraction approach\n•Resulting ICERs depended heavily on assumptions and selection of input data\n•Annual incidence of RSV Hospitalization\n•Vaccine costs (e.g., increase in GSK vaccine price)\n•Base -case in the 3 models:\n•Vaccination would significantly reduce RSV disease burden in older adults \n•VE clinical trials data and assumptions support impact on disease reduction\n•Economic value of RSV vaccines appear to be costly and could be cost-effective \n•RSV incidence, related healthcare costs, initial VE and duration combined with reasonable \nvaccine price would determine the cost-effectiveness value of RSV vaccination\nAcknowledgements \nFrom NCIRD/CDC\n•Michael Melgar\n•Jamison Pike\n•Fiona Havers\n•Amadea Britton\nAlso:\n•Adult RSV working group members\n•Andrew Leidner and the Econ Team members at ISD/NCIRD\n27", "summary": "Economics of Vaccinating U.S. Adults ≥60  years -old against  Respiratory Syncytial Virus UPDATED SUMMARY COMPARING MODELS FROM: GSK,Pfizer AND University of Michigan -CDC Ismael R. Ortega -Sanchez, PhD NCIRD/CDC ACIP Meeting, June 21, 2023 1Disclaimer : The findings and conclusions in this report are those of the authors and do not necessarily represent the views of  the Centers for Disease Control and Prevention.  National Center for Immunization & Respiratory Diseases Conflict of interest…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/05-RSV-Adults-Ortega-Sanchez-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 27}
{"title": "06 RSV Adults Melgar 508", "content": "Centers for Disease Control and Prevention\nEvidence to Recommendations Framework\nRespiratory Syncytial Virus (RSV) in Adults\nPfizer bivalent RSVpreF vaccine in older adults \nGSK adjuvanted RSVPreF3 vaccine in older adults\nMichael Melgar, MD\nAmadea Britton, MD\nAdvisory Committee on Immunization Practices\nJune 21, 2023\n2Evidence to Recommendations ( EtR) Framework\nPolicy Questions\n▪Should a single dose of Pfizer bivalent RSVpreF vaccine (120µg antigen, 1 dose IM), \nrather than no vaccine, be recommended in persons aged ≥65 years?\n▪Should a single dose of Pfizer bivalent RSVpreF vaccine (120µg antigen, 1 dose IM), \nrather than no vaccine, be recommended in persons aged 60 –64 years?\n▪Should a single dose of GSK RSVPreF3 vaccine (120µg antigen + AS01Eadjuvant, 1 \ndose IM), rather than no vaccine, be recommended in persons aged ≥65 years?\n▪Should a single dose of GSK RSVPreF3 vaccine (120µg antigen + AS01Eadjuvant, 1 \ndose IM), rather than no vaccine, be recommended in persons aged 60 –64 years?\n3Evidence to Recommendations ( EtR) Framework\nEtRDomain Question(s)\nPublic Health Problem ▪Is the problem of public health importance?\nBenefits and Harms ▪How substantial are the desirable anticipated effects?\n▪How substantial are the undesirable anticipated effects?\n▪Do the desirable effects outweigh the undesirable effects?\nValues ▪Does the target population feel the desirable effects are large relative \nto the undesirable effects?\n▪Is there important variability in how patients value the outcome?\nAcceptability ▪Is the intervention acceptable to key stakeholders?\nFeasibility ▪Is the intervention feasible to implement?\nResource Use ▪Is the intervention a reasonable and efficient allocation of resources?\nEquity ▪What would be in the impact of the intervention on health equity?\n4Evidence to Recommendations ( EtR) Framework\nEtR Domain\nPublic Health Problem\nBenefits and Harms\nValues\nAcceptability\nFeasibility\nResource Use\nEquity\n5Evidence to Recommendations ( EtR) Framework\nManufacturer -specific data will be presentedEtRDomain\nPublic Health Problem\nBenefits and Harms\nValues\nAcceptability\nFeasibility\nResource Use\nEquity\n6Evidence to Recommendations ( EtR) Framework\nUse of RSV vaccines broadly will be presentedEtRDomain\nPublic Health Problem\nBenefits and Harms\nValues\nAcceptability\nFeasibility\nResource Use\nEquity\nBenefits and Harms\n-How substantial are the desirable anticipated effects?\n-How substantial are the undesirable anticipated effects?\n-Do the desirable effects outweigh the undesirable effects?\n8Benefits and Harms\n▪Pfizer bivalent RSVpreF vaccine \n–Grading of Recommendations, Assessment, Development and \nEvaluation ( GRADE ) Summary\n–Modeling potential number of RSV -attributable illnesses prevented\n▪GSK adjuvanted RSVPreF3 vaccine\n–GRADE Summary\n–Modeling potential number of RSV -attributable illnesses prevented\n9GRADE Framework: PICO Question\n▪Population Persons aged ≥60 years\nIntervention Pfizer bivalent RSVpreF vaccine (120µg antigen, 1 dose IM) \n-or-\nGSK RSVPreF3 vaccine (120 μg antigen + AS01Eadjuvant, 1 dose IM)\nComparison No RSV vaccine\nOutcomes ▪RSV lower respiratory tract illness/disease (LRTI/LRTD)\n▪Medically attended RSV LRTI/LRTD\n▪Hospitalization for RSV respiratory illness\n▪Severe RSV respiratory illness requiring supplemental O2 or other\nrespiratory support\n▪Death due to RSV respiratory illness\n▪Serious Adverse Events (SAEs)\n▪Inflammatory neurologic events (e.g., Guillain -Barré syndrome)\n▪Reactogenicity (grade ≥3)\n10GRADE Framework: PICO Question\n▪Population Persons aged ≥60 years\nIntervention Pfizer bivalent RSVpreF vaccine (120µg antigen, 1 dose IM) \n-or-\nGSK RSVPreF3 vaccine (120 μg antigen + AS01Eadjuvant, 1 dose IM)\nComparison No RSV vaccine\nOutcomes ▪RSV lower respiratory tract illness/disease (LRTI/LRTD)\n▪Medically attended RSV LRTI/LRTD\n▪Hospitalization for RSV respiratory illness\n▪Severe RSV respiratory illness requiring supplemental O2 or other\nrespiratory support\n▪Death due to RSV respiratory illness\n▪Serious Adverse Events (SAEs)\n▪Inflammatory neurologic events (e.g., Guillain -Barré syndrome)\n▪Reactogenicity (grade ≥3)\n11Case definitions of lower respiratory tract \nillness/disease were not aligned across clinical trials\n▪Pfizer\n▪RSV LRTI with ≥2 lower respiratory \nsigns/symptoms (co -primary outcome)\n▪RSV LRTI with ≥3 lower respiratory \nsigns/symptoms (co -primary outcome)\n▪Lower respiratory signs/symptoms:\n–Sputum, cough, shortness of breath, \nwheezing, tachypnea▪GSK\n▪RSV LRTD (primary outcome)\n–≥2 lower respiratory symptoms or \nsigns , including ≥1 sign, OR\n–≥3 lower respiratory symptoms\n▪Lower respiratory symptoms :\n–Sputum, cough, dyspnea\n▪Lower respiratory signs :\n–Wheezing, crackles/rhonchi, \ntachypnea, hypoxemia, O2\nsupplementation\n12Case definitions of lower respiratory tract \nillness/disease were not aligned across clinical trials\n▪Pfizer\n▪RSV LRTI with ≥2 lower respiratory \nsigns/symptoms (co -primary outcome)\n▪RSV LRTI with ≥3 lower respiratory \nsigns/symptoms (co-primary outcome)\n▪Lower respiratory signs/symptoms:\n–Sputum, cough, shortness of breath, \nwheezing, tachypnea▪GSK\n▪RSV LRTD (primary outcome)\n–≥2 lower respiratory symptoms or \nsigns , including ≥1 sign, OR\n–≥3 lower respiratory symptoms\n▪Lower respiratory symptoms :\n–Sputum, cough, dyspnea\n▪Lower respiratory signs :\n–Wheezing, crackles/rhonchi, \ntachypnea, hypoxemia, O2\nsupplementation\n13GRADE: Pfizer bivalent RSVpreF\n14Pfizer, Benefits: vaccine efficacy estimates\nOutcome​ Importance Data sourcesVaccine efficacy (%)a\n(95% confidence interval)Concerns in certainty \nassessment\nBenefits\nRSV Lower Respiratory Tract Illness \n(LRTI)bCritical\nOne phase 3 RCTc,\n-10.6 months mean \nfollow up time \nunder surveillance, \nincluding partial \nseason 2d\n-31,986 person -\nyears under \nsurveillance84.4 (59.6, 95.2)\nVaccine: n=5, Placebo: n=32Indirectness (serious)e\nMedically attended RSV LRTIbCritical81.0 (43.5, 95.2)\nVaccine: n=4, Placebo: n=21Indirectness (serious)e\nHospitalization for RSV respiratory \nillnessImportant66.7 ( -315, 99.4)\nVaccine: n=1, Placebo: n=3Indirectness (serious)e\nImprecision (very \nserious)f\nSevere RSV respiratory illness \nrequiring O2/respiratory supportImportant0 (-7750, 98.7)\nVaccine: n=1, Placebo: n=1Indirectness (serious)e\nImprecision (very \nserious)f\nDeath due to RSV respiratory illness ImportantVaccine: n=0/16,010 person -years\nPlacebo: n=0/15,976 person -yearsUnable to evaluateg\naEfficacy estimates were independently calculated using counts of events and total person -time available from the Pfizer pivotal phase 3 trial. Data provided by manufacturer. \nEfficacy was calculated as 1 –incidence rate ratio. Events of each outcome were included if they occurred on or after day 15 af ter injection. Manufacturer used the same \nmethodology to calculate efficacy estimates.\nbPfizer pivotal phase 3 trial included co -primary outcomes of LRTI with ≥2 lower respiratory signs or symptoms, and LRTI with ≥3 lower respiratory signs or symptoms. In GRADE, \nthe outcome of LRTI with ≥3 lower respiratory signs or symptoms was used.\nc RCT = randomized controlled trial. Walsh EE, et al. Efficacy and Safety of a Bivalent RSV Prefusion F Vaccine in Older Adults . 2023. NEJM. https://doi.org/10.1056/nejmoa2213836\ndMean time from vaccination to end of efficacy follow up, including a gap in RSV surveillance, was 12 months per participant. Among participants who contributed to partial \nSeason 2, this was 13.9 months per participant.\ne Underrepresentation of adults aged ≥75 years and adults with congestive heart failure. Exclusion of adults with immune compro mise.\nf95% confidence interval for measure of absolute risk included potential for both benefit and harm. Fragility of estimates.\ngNo RSV -associated deaths were recorded.\n15Pfizer, Benefits: vaccine efficacy estimates\nOutcome​ Importance Data sourcesVaccine efficacy (%)a\n(95% confidence interval)Concerns in certainty \nassessment\nBenefits\nRSV Lower Respiratory Tract Illness \n(LRTI)bCritical\nOne phase 3 RCTc,\n-10.6 months mean \nfollow up time \nunder surveillance, \nincluding partial \nseason 2d\n-31,986 person -\nyears under \nsurveillance84.4 (59.6, 95.2)\nVaccine: n=5, Placebo: n=32Indirectness (serious)e\nMedically attended RSV LRTIbCritical81.0 (43.5, 95.2)\nVaccine: n=4, Placebo: n=21Indirectness (serious)e\nHospitalization for RSV respiratory \nillnessImportant66.7 ( -315, 99.4)\nVaccine: n=1, Placebo: n=3Indirectness (serious)e\nImprecision (very \nserious)f\nSevere RSV respiratory illness \nrequiring O2/respiratory supportImportant0 (-7750, 98.7)\nVaccine: n=1, Placebo: n=1Indirectness (serious)e\nImprecision (very \nserious)f\nDeath due to RSV respiratory illness ImportantVaccine: n=0/16,010 person -years\nPlacebo: n=0/15,976 person -yearsUnable to evaluateg\naEfficacy estimates were independently calculated using counts of events and total person -time available from the Pfizer pivotal phase 3 trial. Data provided by manufacturer. \nEfficacy was calculated as 1 –incidence rate ratio. Events of each outcome were included if they occurred on or after day 15 af ter injection. Manufacturer used the same \nmethodology to calculate efficacy estimates.\nbPfizer pivotal phase 3 trial included co -primary outcomes of LRTI with ≥2 lower respiratory signs or symptoms, and LRTI with ≥3 lower respiratory signs or symptoms. In GRADE, \nthe outcome of LRTI with ≥3 lower respiratory signs or symptoms was used.\nc RCT = randomized controlled trial. Walsh EE, et al. Efficacy and Safety of a Bivalent RSV Prefusion F Vaccine in Older Adults . 2023. NEJM. https://doi.org/10.1056/nejmoa2213836\ndMean time from vaccination to end of efficacy follow up, including a gap in RSV surveillance, was 12 months per participant. Among participants who contributed to partial \nSeason 2, this was 13.9 months per participant.\ne Underrepresentation of adults aged ≥75 years and adults with congestive heart failure. Exclusion of adults with immune compro mise.\nf95% confidence interval for measure of absolute risk included potential for both benefit and harm. Fragility of estimates.\ngNo RSV -associated deaths were recorded.\n16Pfizer: RSV lower respiratory tract illness (LRTI), \ndefined by ≥3 lower respiratory signs or symptoms\nPopulationCase split \n(vaccine/placebo)aManufacturer -calculated \nvaccine efficacy, % (95% CI)\nAll (age ≥60 years) 5/32 84.4 (59.6, 95.2)\nAge ≥65 years 3/23 87.0 (56.8, 97.5)\nAge ≥70 years 1/11 90.9 (37.5, 99.8)\nAge ≥75 years 1/7 85.7 (-11.2, 99.7)b\nAge ≥80 years 0/4 100.0 (-51.5, 100.0)b\na Pfizer pivotal phase 3 trial (Walsh EE, et al. NEJM 2023 https://doi.org/10.1056/nejmoa2213836 ). Events of each \noutcome were included if they occurred on or after day 15 after injection. Average time, across participants, from \nvaccination to end of efficacy follow up was 12 months, including unpublished data provided by manufacturer from \npartial season 2. Total 36,127 participants (31,986 person -years) under surveillance.\nbHighlighted text indicates that evidence of statistically significant efficacy is lacking.\n17PopulationCase split \n(vaccine/placebo)aManufacturer -calculated \nvaccine efficacy, % (95% CI)\n≥1 pre -existing comorbidity of \ninterestb 4/20 80.0 (40.3, 95.0)\n≥1 pre -existing cardiorespiratory \ncomorbidityc 3/11 72.7 ( -3.2, 95.1)d\nAdults who are frail Not assessedd\na Pfizer pivotal phase 3 trial (Walsh EE, et al. NEJM 2023 https://doi.org/10.1056/nejmoa2213836 ). Events of each outcome were \nincluded if they occurred on or after day 15 after injection. Average time, across participants, from vaccination to end of e fficacy \nfollow up was 12 months, including unpublished data provided by manufacturer from partial season 2. Total 36,127 participants\n(31,986 person -years) under surveillance.\nb COPD, asthma, diabetes mellitus, congestive heart failure, liver or renal disease\ncCOPD, asthma, congestive heart failure\ndHighlighted text indicates that evidence of statistically significant efficacy is lacking.Pfizer: RSV lower respiratory tract illness (LRTI), \ndefined by ≥3 lower respiratory signs or symptoms\n18Pfizer, Harms: relative risk\nOutcome​ Importance Data sourcesRelative risk estimatea\n(95% confidence interval)Concerns in certainty \nassessment\nHarms\nSerious adverse events \n(SAEs)CriticalOne phase 3 RCT,\none phase 1/2 RCTb1.04 (0.94, 1.15)\nN=36,953 total participantsNone serious\nInflammatory neurologic \neventsImportantOne phase 3 RCTc\none phase 1/2 RCTcVaccine: n=3/18,622 participantsd\nPlacebo: n=0/18,335 participantseImprecision\n(very serious)f,g\nReactogenicity (grade ≥3) ImportantOne phase 3 RCTh\none phase 1/2 RCTh1.43 (0.85, 2.39)\nN=7,164 total participantsImprecision\n(serious)f\naPooled relative risk estimates were independently calculated using counts of events and participants in the Pfizer pivotal ph ase 3 trial (Walsh EE et \nal. NEJM 2023 https://doi.org/10.1056/nejmoa2213836 ), as well as from a placebo -controlled phase 1/2 dosing selection study ( Falsey AR, et al. J \nInfect Dis. 2022 https://doi.org/10.1093/infdis/jiab611 ). Data provided by manufacturer.\nbAfter dose 1, but before dose 2 (day 61). RCT = randomized controlled trial.\ncWithin 42 days after injection. RCT = randomized controlled trial.\ndIn the Pfizer pivotal phase 3 trial, 2 events of Guillain -Barré syndrome (GBS) and 1 event of motor -sensory axonal polyneuropat hy were reported \nwithin 42 days after vaccination with RSVpreF , compared with zero in the placebo arm. One additional case of GBS was reported 8 months after \nvaccination with RSVpreF and one additional case of GBS was reported 14 months after placebo receipt. No events were recorded in the phase 1/2 \nformulation selection study.\ne Measures of relative and absolute risk were not calculated due to zero events within 42 days in placebo recipients.\nf95% confidence interval for measure of absolute risk included potential for both benefit and harm.\ng Fragility of estimate.\nhWithin 7 days after vaccination. RCT = randomized controlled trial.\n19aPooled relative risk estimates were independently calculated using counts of events and participants in the Pfizer pivotal ph ase 3 trial (Walsh EE et \nal. NEJM 2023 https://doi.org/10.1056/nejmoa2213836 ), as well as from a placebo -controlled phase 1/2 dosing selection study ( Falsey AR, et al. J \nInfect Dis. 2022 https://doi.org/10.1093/infdis/jiab611 ). Data provided by manufacturer.\nbAfter dose 1, but before dose 2 (day 61). RCT = randomized controlled trial.\ncWithin 42 days after injection. RCT = randomized controlled trial.\ndIn the Pfizer pivotal phase 3 trial, 2 events of Guillain -Barré syndrome (GBS) and 1 event of motor -sensory axonal polyneuropat hy were reported \nwithin 42 days after vaccination with RSVpreF , compared with zero in the placebo arm. One additional case of GBS was reported 8 months after \nvaccination with RSVpreF and one additional case of GBS was reported 14 months after placebo receipt. No events were recorded in the phase 1/2 \nformulation selection study.\ne Measures of relative and absolute risk were not calculated due to zero events within 42 days in placebo recipients.\nf95% confidence interval for measure of absolute risk included potential for both benefit and harm.\ng Fragility of estimate.\nhWithin 7 days after vaccination. RCT = randomized controlled trial.Pfizer, Harms: relative risk\nOutcome​ Importance Data sourcesRelative risk estimatea\n(95% confidence interval)Concerns in certainty \nassessment\nHarms\nSerious adverse events \n(SAEs)CriticalOne phase 3 RCT,\none phase 1/2 RCTb1.04 (0.94, 1.15)\nN=36,953 total participantsNone serious\nInflammatory neurologic \neventsImportantOne phase 3 RCTc\none phase 1/2 RCTcVaccine: n=3/18,622 participantsd\nPlacebo: n=0/18,335 participantseImprecision\n(very serious)f,g\nReactogenicity (grade ≥3) ImportantOne phase 3 RCTh\none phase 1/2 RCTh1.43 (0.85, 2.39)\nN=7,164 total participantsImprecision\n(serious)f\nTotal of 3inflammatory neurologic events reported \nwithin 42 days of vaccination with RSVpreF among \n20,255 older adults across all clinical trials\n20Pfizer: Total inflammatory neurologic events reported within 42 \ndays of vaccination across all clinical trials\nParticipant \nageCountry Reported as Onset Trial Work group case \nreview\n66 years United \nStatesGBSa, Brighton \nCollaborationblevel 114 days post -\nvaccinationPivotal phase 3 trial, \nrandomized, blinded, placebo -\ncontrolledClinical course more \nconsistent with CIDPc\n66 years Japan GBSa, Miller -Fisher \nvariant, Brighton \nCollaborationblevel 410 days post -\nvaccinationPivotal phase 3 trial, \nrandomized, blinded, placebo -\ncontrolledPossible GBS (Miller \nFisher syndrome) \nthough other causes \nare also possible\n68 years Argentina Motor -sensory \naxonal \npolyneuropathy*\n*Site investigator reported \nas not associated with \nvaccination21 days post -\nvaccination*\n*Participant \nreported some \nsymptoms preceded \nvaccinationPivotal phase 3 trial, \nrandomized, blinded, placebo -\ncontrolledUndifferentiated \nmotor -sensory axonal \npolyneuropathy\naGBS = Guillain Barre syndrome\nbhttps://brightoncollaboration.us/guillain -barre -and-miller -fisher -syndromes -case -definition -companion -guide/\ncCIDP = chronic inflammatory demyelinating polyneuropathy\n21Background incidence of Guillain -Barré syndrome \namong older adults \naSejvar JJ, et al. Population incidence of Guillain -Barré syndrome: a systematic review and meta -analysis. Neuroepidemiology. 20 11;36(2):123 -33. https://doi.org/10.1159/000324710\nbShui IM, et al. Guillain -Barré syndrome incidence in a large United States cohort (2000 -2009). Neuroepidemiology. 2012;39(2):10 9-15. https://doi.org/10.1159/000339248\nAge group, \nyearsAnnual rate per 100,000 \npopulation (95% CI)\n0–9 0.62 (0.52 –0.75)\n10–19 0.75 (0.60 –0.92)\n20–29 0.90 (0.67 –1.19)\n30–39 1.07 (0.74 –1.56)\n40–49 1.29 (0.80 –2.06)\n50–59 1.54 (0.87 –2.74)\n60–69 1.85 (0.94 –3.64)\n70–79 2.22 (1.01 –4.86)\n80–89 2.66 (1.09 –6.48)Meta -analysisa, 13 studies, North America & Europe\nAge group, \nyearsAnnual rate per 100,000 population\n(95% CI)\nFemale Male\n0–4 0.51 (0.24 –0.78) 0.39 (0.16 –0.61)\n5–17 0.43 (0.29 –0.57) 0.62 (0.46 –0.79)\n18–24 0.64 (0.39 –0.89) 0.75 (0.47 –1.03)\n25–49 1.00 (0.85 –1.15) 1.39 (1.20 –1.57)\n50–64 2.19 (1.90 –2.50) 2.85 (2.49 –3.21)\n≥65 4.68 (4.14 –5.21) 7.06 (6.31 –7.81)Vaccine Safety Datalink, United States, 2000 –2009b\n22Estimated incidence of Guillain -Barre syndrome (GBS) following other \nrecommended vaccinations\n▪Seasonal influenza vaccinesa: The data on the association between GBS and \nseasonal flu vaccination are variable and inconsistent across flu seasons. If there is \nan increased risk of GBS following flu vaccination it is small, on the order of 1–2 \nadditional cases per million doses of flu vaccine administered.\n▪Recombinant zoster vaccineb: 3 excess cases per million doses administered\n–6 excess cases per million first doses administered, no increased risk following \nthe second dose\na https://www.cdc.gov/flu/prevent/guillainbarre.htm#how1\nb https://www.fda.gov/vaccines -blood -biologics/safety -availability -biologics/fda -requires -warning -about -guillain -barre -syndrome -gbs-be-included -prescribing -information -\nshingrix\n23Summary of GRADE for Pfizer RSVpreF vaccine in older adults\nOutcome​ Importance Design\n(# of studies)​Findings​ Evidence\ntype​\nBenefits\nRSV Lower Respiratory Tract \nDisease (LTRI)Critical RCT (1) Pfizer RSVpreF likely reduces RSV LRTI. Moderate\nMedically attended RSV LRTI Critical RCT (1) Pfizer RSVpreF likely reduces medically attended RSV LRTI. Moderate\nHospitalization for RSV \nrespiratory illnessImportant RCT (1)Pfizer RSVpreF may reduce hospitalization for RSV respiratory \nillness, but the effect is very uncertain.Very low\nSevere RSV respiratory \nillness requiring \nO2/respiratory supportImportant RCT (1)Pfizer RSVpreF may not impact severe RSV respiratory illness \nrequiring supplemental oxygen or other respiratory support, but \nthe effect is very uncertain.Very low\nDeath due to RSV respiratory \nillnessImportant RCT (1) No events observedUnable to \nevaluate\nHarms\nSerious adverse events​ Critical RCT (2) Pfizer RSVpreF results in little to no differences in SAEs. High\nInflammatory neurologic \neventsImportant RCT (2) Pfizer RSVpreF may increase inflammatory neurologic events. Low\nReactogenicity ​(grade ≥3) Important RCT (2) Pfizer RSVpreF likely increases severe reactogenicity events. Moderate\n24\nSummary of GRADE for Pfizer RSVpreF vaccine in older adults\nOverall evidence rating: Moderate certainty\n25RSV-NET estimated annual hospitalizations per \n100,000 adults: 2016 –2017 to 2019 –2020\n050100150200250300350400450\n18-49 yrs 50-59 yrs 60-64 yrs ≥65 yrs 65-69 yrs 70-74 yrs ≥75 yrsAnnual RSV -associated hospitalizations \nper 100,000 population2016-17\n2017-18\n2018-19\n2019-20\nCDC RSV -NET unpublished data. Estimates are adjusted for under -testing and incomplete test sensitivity. https://www.cdc.gov/rsv/research/rsv -net/index.html\n26Modeling potential RSV -attributable illnesses prevented:\nPfizer RSVpreF\n▪Included in economic analysis performed by U. Michigan, using published incidence \nestimates and RSV -NET estimated annual hospitalizations per 100,000 adults\n▪Timeframe: 2 RSV seasons (assumed duration of vaccine protection)\nNumber prevented per 1 \nmillion vaccinations among:\nAdults aged ≥65 yearsNumber prevented per 1 \nmillion vaccinations among:\nAdults aged 60 –64 years\nOutpatient visitsa25,000 19,000\nHospitalizationsb 2,500 960\nDeathsc130 37\naIncidence rates of RSV illness requiring outpatient visit taken from McLaughlin et al, OFID (2022) . Vaccine efficacy (VE) against this outcome assumed to be equal to that against \nmedically attended acute respiratory illness (ARI) caused by RSV (Pfizer RENOIR trial, including unpublished data from partia l season 2 follow up).\nbIncidence rates of RSV hospitalization taken from RSV -NET 2016 –2020 (unpublished). VE against RSV -associated hospitalization as sumed to be equal to that against medically attended \nlower respiratory tract illness (LRTI) with ≥3 symptoms, caused by RSV (Pfizer RENOIR trial, unpublished).\ncProbability of in -hospital death among adults hospitalized for RSV taken from RSV -NET 2016 –2020 (unpublished). VE against RSV -associated death assumed to be equal to that against \nmedically attended lower respiratory tract illness (LRTI) with ≥3 symptoms, caused by RSV (Pfizer RENOIR trial, unpublished).\n27Pfizer, post -marketing safety requirements and commitments\nStudy​ Aim Design Final protocol submission to FDA Study completion date\nC3671031aEvaluate risk of GBSRetrospective cohort, \nclaims -basedNovember 30, 2023 May 31, 2029\nC3671037Evaluate risk of atrial \nfibrillationbActive surveillance study November 30, 2023 February 28, 2027\nC3671013 (main \nphase 3 trial)Evaluate safety and \nimmunogenicity of \nrevaccinationClinical trial Submitted March 31, 2025\nMay 31, 2023 Approval Letter -ABRYSVO (fda.gov)aPost -marketing requirement under Section 505(o) of the Federal Food, Drug, and Cosmetic Act \nbA numerical imbalance in events of atrial fibrillation was noted in the main phase 3 trial, with 10 events in the RSVpreF group and 4 events in the \nplacebo group, within 1 month following vaccination.\nVaccines and Related Biological Products Advisory Committee February 28 -March 1, 2023 Meeting Briefing Document -FDA: Applican t Pfizer\n28Benefits and Harms Pfizer bivalent RSVpreF vaccine\n▪How substantial are the desirable anticipated effects among adults \naged ≥65 years (relative to no RSV vaccine)?\n–How substantial is the anticipated protective effect against:\n•RSV lower respiratory tract disease (LRTD)\n•Medically attended RSV LRTD\n•Hospitalization for RSV respiratory illness\n•Severe RSV respiratory illness requiring supplemental O2/respiratory \nsupport\n•Death due to RSV respiratory illness\nMinimal Small Moderate Large Varies Don’t know\n29Benefits and Harms Pfizer bivalent RSVpreF vaccine\n▪How substantial are the undesirable anticipated effects among \nadults aged ≥65 years (relative to no RSV vaccine)?\n–How substantial is the anticipated effect on:\n•Serious Adverse Events (SAEs)\n•Inflammatory neuropathy (e.g., Guillain -Barré Syndrome)\n•Reactogenicity (grade ≥3)\nMinimal Small Moderate Large Varies Don’t know\n30Benefits and Harms Pfizer bivalent RSVpreF vaccine\n▪Do the desirable effects outweigh the undesirable effects among \nadults aged ≥65 years ?\n–What is the balance between the desirable effects relative to \nthe undesirable effects?\nFavors intervention (Pfizer RSVpreF vaccine)\nFavors comparison (no vaccine)\nFavors both\nFavors neither\nUnclear\nMinority opinion\n31Benefits and Harms Pfizer bivalent RSVpreF vaccine\n▪How substantial are the desirable anticipated effects among adults \naged 60–64 years (relative to no RSV vaccine)?\n–How substantial is the anticipated protective effect against:\n•RSV lower respiratory tract disease (LRTD)\n•Medically attended RSV LRTD\n•Hospitalization for RSV respiratory illness\n•Severe RSV respiratory illness requiring supplemental O2/respiratory \nsupport\n•Death due to RSV respiratory illness\nMinimal Small Moderate Large Varies Don’t know\n32Benefits and Harms Pfizer bivalent RSVpreF vaccine\n▪How substantial are the undesirable anticipated effects among \nadults aged 60–64 years (relative to no RSV vaccine)?\n–How substantial is the anticipated effect on:\n•Serious Adverse Events (SAEs)\n•Inflammatory neuropathy (e.g., Guillain -Barré Syndrome)\n•Reactogenicity (grade ≥3)\nMinimal Small Moderate Large Varies Don’t know\n33Benefits and Harms Pfizer bivalent RSVpreF vaccine\n▪Do the desirable effects outweigh the undesirable effects among \nadults aged 60–64 years ?\n–What is the balance between the desirable effects relative to \nthe undesirable effects?\nFavors intervention (Pfizer RSVpreF vaccine)\nFavors comparison (no vaccine)\nFavors both\nFavors neither\nUnclear\nMinority opinion\n34GRADE: GSK adjuvanted RSVPreF3\n35GSK, Benefits: vaccine efficacy estimates\nOutcome​ Importance Data sourcesVaccine efficacy of a single dose (%)a\n(95% confidence interval)Concerns in certainty \nassessment\nBenefits\nRSV Lower Respiratory \nTract Disease (LTRD)Critical\nOne phase 3 RCTb, \n-15.3 months mean \nfollow up time, \nincluding season 2c\n-31,932 –32,023 \nperson -years under \nsurveillance, varied \nby outcome74.6 (62.1, 83.5)\nVaccine: n=30, Placebo: n=139Indirectness (serious)d\nMedically attended RSV \nLRTDCritical77.5 (57.9, 89.0)\nVaccine: n=12, Placebo: n=63Indirectness (serious)d\nHospitalization for RSV \nrespiratory illnessImportant76.4 ( -111, 99.5)\nVaccine: n=1, Placebo: n=5Indirectness (serious)d\nImprecision (very serious)e\nSevere RSV respiratory \nillness requiring \nO2/respiratory supportImportant76.4 ( -111, 99.5)\nVaccine: n=1, Placebo: n=5Indirectness (serious)d\nImprecision (very serious)e\nDeath due to RSV \nrespiratory illnessImportantVaccine: n=0/ 14,677 person -years\nPlacebo: n=0/17,346 person -yearsUnable to evaluatef\naEfficacy estimates were independently calculated using counts of events and total person -time available from the GSK pivotal ph ase 3 trial. Data provided by manufacturer. \nEfficacy was calculated as 1 –incidence rate ratio. Events of each outcome were included if they occurred on or after day 15 af ter injection. Due to exclusion of follow up time after \nRSVPreF3 dose 2 among participants randomized to annual re -vaccination, person -time in the placebo arm exceeded that in the inte rvention arm. CDC method of efficacy \nestimation differed from manufacturer method (Poisson model adjusted by season, participant age, & region). Adjustment by sea sonresulted in substantially different estimates.\nb RCT = randomized controlled trial. Papi A, et al. Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older Adults. 2023. NEJM. https://doi.org/10.1056/nejmoa2209604\ncMean efficacy follow up time inclusive of person -time after dose 2 of RSVPreF3 was 16.6 months. Median time of efficacy follow up was 17.8 months.\ndUnderrepresentation of adults aged ≥75 years, adults with congestive heart failure, and frail adults. Exclusion of adults wit h immune compromise.\ne 95% confidence interval for measure of absolute risk included potential for both benefit and harm. Fragility of estimates.\nfNo RSV -associated deaths were recorded.\n36GSK, Benefits: vaccine efficacy estimates\nOutcome​ Importance Data sourcesVaccine efficacy of a single dose (%)a\n(95% confidence interval)Concerns in certainty \nassessment\nBenefits\nRSV Lower Respiratory \nTract Disease (LTRD)Critical\nOne phase 3 RCTb, \n-15.3 months mean \nfollow up time, \nincluding season 2c\n-31,932 –32,023 \nperson -years under \nsurveillance, varied \nby outcome74.6 (62.1, 83.5)\nVaccine: n=30, Placebo: n=139Indirectness (serious)d\nMedically attended RSV \nLRTDCritical77.5 (57.9, 89.0)\nVaccine: n=12, Placebo: n=63Indirectness (serious)d\nHospitalization for RSV \nrespiratory illnessImportant76.4 ( -111, 99.5)\nVaccine: n=1, Placebo: n=5Indirectness (serious)d\nImprecision (very serious)e\nSevere RSV respiratory \nillness requiring \nO2/respiratory supportImportant76.4 ( -111, 99.5)\nVaccine: n=1, Placebo: n=5Indirectness (serious)d\nImprecision (very serious)e\nDeath due to RSV \nrespiratory illnessImportantVaccine: n=0/ 14,677 person -years\nPlacebo: n=0/17,346 person -yearsUnable to evaluatef\naEfficacy estimates were independently calculated using counts of events and total person -time available from the GSK pivotal ph ase 3 trial. Data provided by manufacturer. \nEfficacy was calculated as 1 –incidence rate ratio. Events of each outcome were included if they occurred on or after day 15 af ter injection. Due to exclusion of follow up time after \nRSVPreF3 dose 2 among participants randomized to annual re -vaccination, person -time in the placebo arm exceeded that in the inte rvention arm. CDC method of efficacy \nestimation differed from manufacturer method (Poisson model adjusted by season, participant age, & region). Adjustment by sea sonresulted in substantially different estimates.\nb RCT = randomized controlled trial. Papi A, et al. Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older Adults. 2023. NEJM. https://doi.org/10.1056/nejmoa2209604\ncMean efficacy follow up time inclusive of person -time after dose 2 of RSVPreF3 was 16.6 months. Median time of efficacy follow up was 17.8 months.\ndUnderrepresentation of adults aged ≥75 years, adults with congestive heart failure, and frail adults. Exclusion of adults wit h immune compromise.\ne 95% confidence interval for measure of absolute risk included potential for both benefit and harm. Fragility of estimates.\nfNo RSV -associated deaths were recorded.\n37GSK: RSV lower respiratory tract disease (LRTD)\nAge group \nin yearsCase split \n(vaccine/placebo)aManufacturer -calculated vaccine efficacyb, % (CI)\nNo adjustment by season Adjusted by season\n≥60 (all) 30/139 74.5 (60.0, 84.5) 67.2 (48.2, 80.0)\n≥65 25/100 70.3 (53.5, 81.6) 61.2 (39.0, 76.1)\n≥70 13/65 76.4 (56.7, 88.1) 69.3 (43.4, 84.6)\n≥75 8/24 Not sharedc49.3 ( -18.2, 80.6)c\n≥80 4/10 52.6 ( -64.2, 89.2)c38.4 ( -118, 86.1)c\na GSK pivotal phase 3 trial ( Papi A, et al. NEJM 2023 https://doi.org/10.1056/nejmoa2209604 ). Events of each outcome were included if they \noccurred on or after day 15 after injection. Median time, across participants, of efficacy follow up was 17.8 months, includi ng unpublished data \nprovided by manufacturer from season 2. Total 24,967 participants ( 31,932 person -years) under surveillance.\nb Calculated using Poisson model, adjusted by season and participant age and region. Adjustment by season resulted in efficacy estimates \nsubstantially different from those estimated by CDC. Due to exclusion of follow up time after dose 2 of RSVPreF3 among partic ipants \nrandomized to annual re -vaccination, person -time follow up in the placebo arm exceeded that in the intervention arm.\nc Highlighted text indicates that evidence of statistically significant efficacy is lacking.\n38GSK: RSV lower respiratory tract disease (LRTD)\nPopulationCase split \n(vaccine/ \nplacebo)aManufacturer -calculated vaccine efficacyb, % (CI)\nNo adjustment by season Adjusted by season\n≥1 pre -existing comorbidity of \ninterestc 16/72 74.5 (55.7, 86.1) 66.7 (41.8, 82.0)\n≥1 pre -existing cardiorespiratory \ncomorbidityd 10/56 80.1 (60.6, 91.0) 73.8 (47.9, 88.2)\nGait speed ≥1.0 m/s ( fit) 20/89 73.4 (56.5, 84.5) 66.2 (44.3, 80.4)\nGait speed 0.4 –0.99 m/s ( pre-frail) 8/47 80.0 (57.3, 91.8) 73.3 (42.4, 89.2)\nGait speed <0.4 m/s or unable to \ncomplete assessment ( frail)2/1 -116 ( -12,800, 88.9)e-148 ( -15,800, 88.2)e\na GSK pivotal phase 3 trial ( Papi A, et al. NEJM 2023 https://doi.org/10.1056/nejmoa2209604 ). Events of each outcome were included if they \noccurred on or after day 15 after injection. Median time, across participants, of efficacy follow up was 17.8 months, includi ng unpublished data \nprovided by manufacturer from season 2. Total 24,967 participants ( 31,932 person -years) under surveillance.\nb Calculated using Poisson model, adjusted by season and participant age and region. Adjustment by season resulted in efficacy estimates \nsubstantially different from those estimated by CDC. Due to exclusion of follow up time after dose 2 of RSVPreF3 among partic ipants randomized to \nannual re -vaccination, person -time follow up in the placebo arm exceeded that in the intervention arm.\nc COPD, asthma, any chronic respiratory/pulmonary disease, diabetes mellitus, chronic heart failure, advanced liver or renal di sease\ndCOPD, asthma, any chronic respiratory/pulmonary disease, chronic heart failure\ne Highlighted text indicates that evidence of statistically significant efficacy is lacking.\n39GSK, Harms: relative risk\nOutcome​ Importance Data sourcesRelative risk estimatea\n(95% confidence interval)Concerns in certainty \nassessment\nHarms\nSerious adverse events (SAEs) CriticalOne phase 3 RCTb,\none phase 1/2 RCTc1.02 (0.91, 1.15)\nN=25,174 total participantsNone serious\nInflammatory neurologic \neventsImportantOne phase 3 RCTd\none phase 1/2 RCTdVaccine: n=0/12,570 participants\nPlacebo: n=0/12,604 participantsUnable to evaluate\nReactogenicity (grade ≥3) ImportantOne phase 3 RCTf\none phase 1/2 RCTg4.06 (1.97, 8.36)\nN=1,955 total participantsNone serious\naPooled relative risk estimates were independently calculated using counts of events and participants in the GSK pivotal phase 3trial ( Papi A, et al. NEJM 2023 \nhttps://doi.org/10.1056/nejmoa2209604 ), as well as from a placebo -controlled phase 1/2 dosing selection study (Leroux -Roels I, et al. J Infect Dis. 2022 \nhttps://doi.org/10.1093/infdis/jiac327 ). Data provided by manufacturer.\nbUp to 6 months after injection\ncAfter dose 1, but before dose 2 (day 61)\ndWithin 42 days after injection\neNo events recorded in studies included in GRADE. One event of Guillain -Barré syndrome (GBS) reported within 42 days after vacci nation in a recipient of the \ninvestigational vaccine in an open label trial without a placebo arm. This study was not included in GRADE assessment due to lack of an unvaccinated \ncomparator. Two events of acute disseminated encephalomyelitis (ADEM) reported in a co -administration study of the investigation al vaccine with standard \ndose seasonal influenza vaccine. Both cases were reported in the co -administration arm within 42 days after the intervention; no ne in the sequential \nadministration control arm. This study was not included in GRADE assessment due to lack of an unvaccinated comparator.\nfWithin 7 days after vaccination\ngWithin 4 days after vaccinationRCT: Randomized control trial\n40GSK, Harms: relative risk\nOutcome​ Importance Data sourcesRelative risk estimatea\n(95% confidence interval)Concerns in certainty \nassessment\nHarms\nSerious adverse events (SAEs) CriticalOne phase 3 RCTb,\none phase 1/2 RCTc1.02 (0.91, 1.15)\nN=25,174 total participantsNone serious\nInflammatory neurologic \neventsImportantOne phase 3 RCTd\none phase 1/2 RCTdVaccine: n=0/12,570 participants\nPlacebo: n=0/12,604 participantsUnable to evaluate\nReactogenicity (grade ≥3) ImportantOne phase 3 RCTf\none phase 1/2 RCTg4.06 (1.97, 8.36)\nN=1,955 total participantsNone serious\naPooled relative risk estimates were independently calculated using counts of events and participants in the GSK pivotal phase 3trial ( Papi A, et al. NEJM 2023 \nhttps://doi.org/10.1056/nejmoa2209604 ), as well as from a placebo -controlled phase 1/2 dosing selection study (Leroux -Roels I, et al. J Infect Dis. 2022 \nhttps://doi.org/10.1093/infdis/jiac327 ). Data provided by manufacturer.\nbUp to 6 months after injection\ncAfter dose 1, but before dose 2 (day 61)\ndWithin 42 days after injection\neNo events recorded in studies included in GRADE. One event of Guillain -Barré syndrome (GBS) reported within 42 days after vacci nation in a recipient of the \ninvestigational vaccine in an open label trial without a placebo arm. This study was not included in GRADE assessment due to lack of an unvaccinated \ncomparator. Two events of acute disseminated encephalomyelitis (ADEM) reported in a co -administration study of the investigation al vaccine with standard \ndose seasonal influenza vaccine. Both cases were reported in the co -administration arm within 42 days after the intervention; no ne in the sequential \nadministration control arm. This study was not included in GRADE assessment due to lack of an unvaccinated comparator.\nfWithin 7 days after vaccination\ngWithin 4 days after vaccinationRCT: Randomized control trial\nTotal of 3inflammatory neurologic events reported \nwithin 42 days of vaccination with RSVpreF3 among \n17,922 older adults across all clinical trials\n41GSK: Total inflammatory neurologic events reported within 42 \ndays of vaccination across all clinical trials\nParticipant \nageCountry Reported as Onset Trial Work group case \nreview\n78 years Japan GBSa, Brighton \nCollaborationb\nlevel 39 days \npost -\nvaccination•Open -label phase 3 trial without a \nplacebo control, evaluating the \nimmunogenicity of different \nrevaccination intervalsLikely GBSa\n71 years South \nAfricaADEMc, fatal*\n*Site investigator \nupdated diagnoses: \nhypoglycemia & \ndementia7 days \npost -\nvaccination•Randomized, blinded co -administration \nstudy with standard dose seasonal \ninfluenza vaccine\n•Case occurred in the simultaneous \nadministration arm of the studyADEMccannot be \nruled out, however, \nother diagnoses \nappear more likely\n71 years South \nAfricaADEMc 22 days \npost -\nvaccination•Randomized, blinded co -administration \nstudy with standard dose seasonal \ninfluenza vaccine\n•Case occurred in the simultaneous \nadministration arm of the studyADEMccannot be \nruled out, however, \nother diagnoses \nappear more likely\naGBS = Guillain Barre syndrome\nbhttps://brightoncollaboration.us/guillain -barre -and-miller -fisher -syndromes -case -definition -companion -guide/\ncADEM = acute disseminated encephalomyelitis\n42Summary of GRADE for GSK RSVPreF3 vaccine in older adults\nOutcome​ Importance Design\n(# of studies)​Findings​ Evidence\ntype​\nBenefits\nRSV Lower Respiratory Tract \nDisease (LTRD)Critical RCT (1) GSK RSVPreF3 likely reduces RSV LRTD. Moderate\nMedically attended RSV \nLRTDCritical RCT (1) GSK RSVPreF3 likely reduces medically attended RSV LRTD. Moderate\nHospitalization for RSV \nrespiratory illnessImportant RCT (1)GSK RSVPreF3 may reduce hospitalization for RSV respiratory \nillness, but the effect is very uncertain.Very low\nSevere RSV respiratory \nillness requiring \nO2/respiratory supportImportant RCT (1)GSK RSVPreF3 may reduce severe RSV respiratory illness requiring \noxygen supplementation or other respiratory support, but the \neffect is very uncertain.Very low\nDeath due to RSV respiratory \nillnessImportant RCT (1) No events observedUnable to \nevaluate\nHarms\nSerious adverse events​ Critical RCT (2) GSK RSVPreF3 results in little to no differences in SAEs. High\nInflammatory neurologic \neventsImportant RCT (2)No events observed in placebo -controlled trials. Three cases \nobserved in clinical trials without placebo controls.Unable to \nevaluate\nReactogenicity ​(grade ≥3) Important RCT (2) GSK RSVPreF3 increases severe reactogenicity events. High\n43\nSummary of GRADE for GSK RSV vaccine in older adults\nOverall evidence rating: Moderate certainty\n44Modeling potential RSV -attributable illnesses prevented:\nGSK RSVPreF3\n▪Included in economic analysis performed by U. Michigan, using published incidence \nestimates and RSV -NET estimated annual hospitalizations per 100,000 adults\n▪Timeframe: 2 RSV seasons (assumed duration of vaccine protection)\nNumber prevented per 1 \nmillion vaccinations among:\nAdults aged ≥65 yearsNumber prevented per 1 \nmillion vaccinations among:\nAdults aged 60 –64 years\nOutpatient visitsa23,000 18,000\nHospitalizationsb 2,300 890\nDeathsc 120 35\naIncidence rates of RSV illness requiring outpatient visit taken from McLaughlin et al, OFID (2022) . Vaccine efficacy (VE) against this outcome assumed to be equal to that against \nmedically attended acute respiratory illness (ARI) caused by RSV (GSK AReSVi -006 trial, including unpublished data from season 2 follow up).\nbIncidence rates of RSV hospitalization taken from RSV -NET 2016 –2020 (unpublished). VE against RSV -associated hospitalization as sumed to be equal to that against medically attended \nlower respiratory tract disease (LRTD) caused by RSV (GSK AReSVi -006 trial, unpublished).\ncProbability of in -hospital death among adults hospitalized for RSV taken from RSV -NET 2016 –2020 (unpublished). VE against RSV -associated death assumed to be equal to that against \nmedically attended lower respiratory tract disease (LRTD) caused by RSV (GSK AReSVi -006 trial, unpublished).\n45GSK, post -marketing safety requirements and commitments\nAim Design Final protocol submission to FDA Study completion date\nEvaluate risk of GBS, \nADEMaSelf-controlled risk interval \ndesignJune 30, 2024 June 30, 2030\nEvaluate risk of atrial \nfibrillationbSelf-controlled risk interval \ndesignJune 30, 2024 June 30, 2030\nMay 23, 2023 Approval Letter -AREXVY (fda.gov)aPost -marketing requirement under Section 505(o) of the Federal Food, Drug, and Cosmetic Act\nbA numerical imbalance in events of atrial fibrillation was noted in the main phase 3 trial, with 7 events in the RSVPreF3 gro upand 1 event in the \nplacebo group, within 1 month following vaccination (dose 1).\nVaccines and Related Biological Products Advisory Committee February 28 -March 1, 2023 Meeting Briefing Document -FDA: Applican t-GSK\n46Benefits and Harms GSK adjuvanted RSVPreF3 vaccine\n▪How substantial are the desirable anticipated effects among adults \naged ≥65 years (relative to no RSV vaccine)?\n–How substantial is the anticipated protective effect against:\n•RSV lower respiratory tract disease (LRTD)\n•Medically attended RSV LRTD\n•Hospitalization for RSV respiratory illness\n•Severe RSV respiratory illness requiring supplemental O2/respiratory \nsupport\n•Death due to RSV respiratory illness\nMinimal Small Moderate Large Varies Don’t know\n47Benefits and Harms GSK adjuvanted RSVPreF3 vaccine\n▪How substantial are the undesirable anticipated effects among \nadults aged ≥65 years (relative to no RSV vaccine)?\n–How substantial is the anticipated effect on:\n•Serious Adverse Events (SAEs)\n•Inflammatory neuropathy (e.g., Guillain -Barré Syndrome)\n•Reactogenicity (grade ≥3)\nMinimal Small Moderate Large Varies Don’t know\n48Benefits and Harms GSK adjuvanted RSVPreF3 vaccine\n▪Do the desirable effects outweigh the undesirable effects among \nadults aged ≥65 years ?\n–What is the balance between the desirable effects relative to \nthe undesirable effects?\nFavors intervention (GSK RSVPreF3 vaccine)\nFavors comparison (no vaccine)\nFavors both\nFavors neither\nUnclear\nMinority opinion\n49Benefits and Harms GSK adjuvanted RSVPreF3 vaccine\n▪How substantial are the desirable anticipated effects among adults \naged 60–64 years (relative to no RSV vaccine)?\n–How substantial is the anticipated protective effect against:\n•RSV lower respiratory tract disease (LRTD)\n•Medically attended RSV LRTD\n•Hospitalization for RSV respiratory illness\n•Severe RSV respiratory illness requiring supplemental O2/respiratory \nsupport\n•Death due to RSV respiratory illness\nMinimal Small Moderate Large Varies Don’t know\n50Benefits and Harms GSK adjuvanted RSVPreF3 vaccine\n▪How substantial are the undesirable anticipated effects among \nadults aged 60–64 years (relative to no RSV vaccine)?\n–How substantial is the anticipated effect on:\n•Serious Adverse Events (SAEs)\n•Inflammatory neuropathy (e.g., Guillain -Barré Syndrome)\n•Reactogenicity (grade ≥3)\nMinimal Small Moderate Large Varies Don’t know\n51Benefits and Harms GSK adjuvanted RSVPreF3 vaccine\n▪Do the desirable effects outweigh the undesirable effects among \nadults aged 60–64 years ?\n–What is the balance between the desirable effects relative to \nthe undesirable effects?\nFavors intervention (GSK RSVPreF3 vaccine)\nFavors comparison (no vaccine)\nFavors both\nFavors neither\nUnclear\nMinority opinion\nResource Use\nIs an RSV vaccine program for older adults a reasonable and efficient \nallocation of resources?\n53Work group considerations\n▪RSV vaccination for older adults could be a cost -effective intervention\n▪There is substantial uncertainty in the net societal costs of an RSV \nvaccination program for older adults, driven by:\n–Uncertainty in vaccine acquisition cost\n•Current assumptions: $200 Pfizer RSVpreF , $270 GSK RSVPreF3\n–Uncertainty in incidence of RSV illness (e.g., hospitalization)\n–Uncertainty in duration of protection from RSV vaccination\n•Current assumption: 2 RSV seasons\n▪Vaccination of older age groups would be more cost effective than \nvaccination of younger age groups\n54Resource Use\n▪Is use of Pfizer bivalent RSVpreF vaccine among adults aged \n≥65 years a reasonable and efficient allocation of resources, \ncompared with no RSV vaccine?\n▪Is use of GSK adjuvanted RSVPreF3 vaccine among adults aged \n≥65 years a reasonable and efficient allocation of resources, \ncompared with no RSV vaccine?\nNo Probably No Probably Yes Yes Varies Don’t know\n55Resource Use\n▪Is use of Pfizer bivalent RSVpreF vaccine among adults aged \n60–64 years a reasonable and efficient allocation of resources, \ncompared with no RSV vaccine?\n▪Is use of GSK adjuvanted RSVPreF3 vaccine among adults aged \n60–64 years a reasonable and efficient allocation of resources, \ncompared with no RSV vaccine?\nNo Probably No Probably Yes Yes Varies Don’t know\nEquity\nWhat would be the impact on health equity of recommending RSV \nvaccines in older adults?\n57The Work Group discussed multiple equity concerns. \n▪Not all persons experience the same risk of RSV disease. \n▪An RSV vaccine might increase equity byprotecting those \ndisproportionately impacted by RSV. \n▪However, if access or uptake of the vaccine is not equal, an \nRSV vaccine might decrease equity.\n▪The age groups in which the vaccine might be recommended \nwere felt to have important equity implications.\nFirst the Work Group considered the impact on equity \nof a recommendation for RSV vaccination in adults \naged 65 years and older .  \nAnticipated impact on equity of an age -based recommendation \nfor RSV vaccination in adults ≥65\nRSV vaccination in adults aged ≥65 years might increase equity by decreasing RSV burden \namong persons from racial and ethnic minority groups and in persons with lower income \nlevels.\nNext the Work Group considered the impact on equity \nof a recommendation for RSV vaccination in adults \naged 60 –64 years .\n61Age of adults hospitalized with RSV, by race and \nethnicity, RSV -NET\nN Median age, years \n(interquartile range)\nAll 9,163 70 (58 –81)\nRace and ethnicity\nWhite, non -Hispanic 5,596 73 (62 –83)\nBlack, non -Hispanic 1,731 60 (50 –70)\nHispanic 713 65 (50 –77)\nAsian or Pacific Islander, non -Hispanic 518 77 (64 –85)\nAmerican Indian or Alaska Native, \nnon-Hispanic56 57 (47 –71)\nCDC RSV -NET data 2015 –2020 (unpublished). https://www.cdc.gov/rsv/research/rsv -net/index.html\n62Age of adults hospitalized with RSV, by race and \nethnicity, RSV -NET\nN Median age, years \n(interquartile range)\nAll 9,163 70 (58 –81)\nRace and ethnicity\nWhite, non -Hispanic 5,596 73 (62 –83)\nBlack, non -Hispanic 1,731 60 (50 –70)\nHispanic 713 65 (50 –77)\nAsian or Pacific Islander, non -Hispanic 518 77 (64 –85)\nAmerican Indian or Alaska Native, \nnon-Hispanic56 57 (47 –71)\nCDC RSV -NET data 2015 –2020 (unpublished). https://www.cdc.gov/rsv/research/rsv -net/index.html\nNumber of chronic conditions by age among Asian, Black, Latino/Hispanic, and \nWhite adults in the National Health Interview Survey (NHIS), 1999 to 2018\nSource: Caraballo C, Herrin J, Mahajan S, et \nal. Temporal Trends in Racial and Ethnic \nDisparities in Multimorbidity Prevalence in \nthe United States, 1999 -2018. Am J Med . \n2022;135(9):1083 -1092.e14. \ndoi:10.1016/j.amjmed.2022.04.010\nNumber of chronic conditions by age among Asian, Black, Latino/Hispanic, and \nWhite adults in the National Health Interview Survey (NHIS), 1999 to 2018\nSource: Caraballo C, Herrin J, Mahajan S, et \nal. Temporal Trends in Racial and Ethnic \nDisparities in Multimorbidity Prevalence in \nthe United States, 1999 -2018. Am J Med . \n2022;135(9):1083 -1092.e14. \ndoi:10.1016/j.amjmed.2022.04.010\nNumber of chronic conditions by age among Asian, Black, Latino/Hispanic, and \nWhite adults in the National Health Interview Survey (NHIS), 1999 to 2018\nSource: Caraballo C, Herrin J, Mahajan S, et \nal. Temporal Trends in Racial and Ethnic \nDisparities in Multimorbidity Prevalence in \nthe United States, 1999 -2018. Am J Med . \n2022;135(9):1083 -1092.e14. \ndoi:10.1016/j.amjmed.2022.04.010\n▪Prevalence of multimorbidity \n(≥2 concurrent conditions) \ndiverged between Black \nindividuals and White \nindividuals\n▪Reached maximum difference \nof 10% among those aged 60 -\n64 years\nDifference in prevalence of multiple chronic conditions by age and \nrace/ethnicity, National Health Interview Survey, 1999 to 2018\nSource: Caraballo C, Herrin J, Mahajan S, et al. Temporal Trends in Racial and Ethnic Disparities in Multimorbidity Prevalence in the United States, 1999 -2018. Am J Med . \n2022;135(9):1083 -1092.e14. doi:10.1016/j.amjmed.2022.04.010\nRSV vaccination in adults aged ≥65 years might increase equity by decreasing RSV burden \namong persons from racial and ethnic minority groups and  persons with lower income \nlevels.\nAn RSV vaccination recommendation that excludes adults aged 60 -64 years might \ndecrease equity by excluding persons from racial and ethnic minority groups that would \nbenefit from the vaccine at earlier ages due to risk conditions. Anticipated impact on equity of an age -based recommendation \nfor RSV vaccination in adults ≥65\n68Shared clinical decision -making \n▪One policy option that the Work Group discussed to address the varied \nrisk of severe RSV disease (e.g., hospitalization) among 60 –64 year -olds \nis shared clinical decision -making (SCDM) for adults aged 60 –64 years. \n▪Ideally, this would allow adults aged 60 –64 years at high risk of RSV \nhospitalization to be vaccinated and decrease age -based racial and \nethnic health disparities. \n▪Prior experience with SCDM might inform the expected impact on \nequity.\n69ACIP recommendations for vaccination based on shared clinical decision -\nmaking (SCDM) that appear (or appeared) on the tables and/or notes of the \nimmunization schedules\n▪Historical: Pneumococcal conjugate vaccination (PCV13) for adults aged 65 years \nand older who do not have an immunocompromising condition, cerebrospinal fluid \nleak, or cochlear implant (recommendation revised in 2021 with introduction of \nPCV15 and PCV20)\n▪Historical: Hepatitis B ( HepB ) vaccination for adults aged 60 years and older with \ndiabetes mellitus (recommendation revised in 2022)\n▪Meningococcal B ( MenB ) vaccination for adolescents and young adults aged 16 –23 \nyears\n▪Human papillomavirus (HPV) vaccination for adults aged 27 –45 years\n70History of Hepatitis B and SCDM\n▪In2011, ACIP recommended Hepatitis B vaccination for all unvaccinated adults with \ndiabetes mellitus aged <60 years butfor unvaccinated adults with diabetes mellitus \naged ≥60 years, ACIP recommended Hepatitis B vaccination at the discretion of \ntheir healthcare provider.\n▪(This recommendation was revised in 2022. Now HepB vaccination is universally \nrecommended for adults aged 19 –59 years and adults aged ≥60 years with risk \nfactors for hepatitis B; adults aged ≥60 years without known risk factors for \nhepatitis B may also receive HepB vaccines). \nSource: Weng MK, Doshani M, Khan MA, et al. Universal Hepatitis B Vaccination in Adults Aged 19 –59 Years: Updated Recommendations of the \nAdvisory Committee on Immunization Practices —United States, 2022. MMWR Morb Mortal Wkly Rep 2022;71:477 –483. \nDOI: http://dx.doi.org/10.15585/mmwr.mm7113a1 external icon .\n71Hep B vaccine coverage remained suboptimal when recommended to be \ngiven at provider discretion \n▪ Lu et al. analyzed 2014 –2018 NHIS \ndata to determine hepatitis B \nvaccination coverage (≥3 doses) \namong adults ≥60 years by \ndiabetes mellitus status\n▪ Hepatitis B vaccination coverage \nremained low among older adults\nwith diabetes mellitus even 7 years \nafter the recommendation was \nmade\nSource: Lu PJ, Hung MC, Srivastav A, Williams WW, Harris AM. Hepatitis B Vaccination Among Adults With Diabetes Mellitus, U.S., 2018. AmJ Prev Med. 2021 Nov;61(5):652 -664. doi: \n10.1016/j.amepre.2021.04.029. Epub 2021 Jul 20. PMID: 34294463; PMCID: PMC9077536.Race and \nethnicity Vaccination\ncoverage with ≥3 Hep B \ndoses\namong adults ≥60 with\ndiabetes mellitusVaccination coverage\nwith ≥3 Hep B doses \namong\nadults ≥60 without \ndiabetes mellitus\nAll 15.3 (13.3 –17.4) 15.9 (14.8 -17.0)\nWhite, non -\nHispanic15.5 (13.1 -18.1) 15.9 (14.7 -17.2)\nBlack, non -\nHispanic17.3 (12.2 -23.9) 13.4 (10.5 -17.2)\nHispanic 9.2 (4.9 -16.7) 16.0 (12.0 -21.0)\nAsian, non -\nHispanic 15.7 (8.1 -28.2) 18.4 (13.4 -24.8)\n72Hep B vaccine coverage remained suboptimal when recommended to be \ngiven at provider discretion \n▪ Lu et al. analyzed 2014 –2018 NHIS \ndata to determine hepatitis B \nvaccination coverage (≥3 doses) \namong adults ≥60 years by \ndiabetes mellitus status\n▪ Hepatitis B vaccination coverage \nremained low among older adults\nwith diabetes mellitus even 7 years \nafter the recommendation was \nmade\n▪ However, coverage may have been \nhigher among Black, non -Hispanic \nolder adults with diabetes mellitus\nSource: Lu PJ, Hung MC, Srivastav A, Williams WW, Harris AM. Hepatitis B Vaccination Among Adults With Diabetes Mellitus, U.S., 2018. AmJ Prev Med. 2021 Nov;61(5):652 -664. doi: \n10.1016/j.amepre.2021.04.029. Epub 2021 Jul 20. PMID: 34294463; PMCID: PMC9077536.Race and \nethnicity Vaccination\ncoverage with ≥3 Hep B \ndoses\namong adults ≥60 with\ndiabetes mellitusVaccination coverage\nwith ≥3 Hep B doses \namong\nadults ≥60 without \ndiabetes mellitus\nAll 15.3 (13.3 –17.4) 15.9 (14.8 -17.0)\nWhite, non -\nHispanic15.5 (13.1 -18.1) 15.9 (14.7 -17.2)\nBlack, non -\nHispanic17.3 (12.2 -23.9) 13.4 (10.5 -17.2)\nHispanic 9.2 (4.9 -16.7) 16.0 (12.0 -21.0)\nAsian, non -\nHispanic 15.7 (8.1 -28.2) 18.4 (13.4 -24.8)\n73In studies assessing knowledge, attitude, and practices around SCDM for \nother vaccines, providers have reported mixed views and understanding \nof recommendations\n1. Kempe A, Lindley MC, O'Leary ST, et al. Shared Clinical Decision -Making Recommendations for Adult Immunization: What Do Physicia ns Think?. J Gen Intern Med . 2021;36(8):2283 -2291. \ndoi:10.1007/s11606 -020-06456 -z\n2. Hurley LP, O'Leary ST, Kobayashi M, et al. Physician survey regarding updated PCV13 vaccine recommendations for adults ≥65 ye ars.J Am Geriatr Soc. 2021;69(9):2612 -2618. doi:10.1111/jgs.17274•Some think that SCDM requires more time \nthan routine recommendations, that SCDM \ncreates confusion, and many do not know \nvaccines recommended for SCDM would be \ncovered by most health insurance1,2\n•Providers unsure of what points to emphasize \nin discussions with patients2•Some in favor of SCDM recommendations \nbecause they give more flexibility in decisions \nabout use of a vaccine1\n74Brief summary of SCDM equity considerations\n▪Ideally SCDM would increase access for adults aged 60 –64 years with \nmedical risk factors for severe RSV disease (disproportionately in racial \nand ethnic groups impacted by RSV at earlier ages)\n▪Limited evidence regarding the impact of conditional \nrecommendations, like SCDM, in older adults suggests they may not \nsubstantially increase uptake in the target population\n▪However, without a recommendation for adults aged 60 –64 years, \nadults with medical risk factors for severe RSV disease would likely face \nadditional barriers to RSV vaccination, increasing health disparities\nAnticipated impact on equity\nRSV vaccination in adults aged ≥65 years might increase equity by decreasing RSV burden \namong persons from racial and ethnic minority groups and  persons with lower income \nlevels.\nRSV vaccination that excludes adults aged 60 -64 years might decrease equity by \nexcluding persons from racial and ethnic minority groups that would benefit from the \nvaccine at earlier ages due to risk conditions. \nRSV vaccination that includes both adults aged 65 and older and adults aged 60 -64 years \nunder shared clinical decision -making (SCDM) would increase access for adults 60 –64 \nwith medical risk factors for severe RSV disease (disproportionately in racial and ethnic \ngroups impacted by RSV at earlier ages). However, SCDM may not substantially increase \nuptake in the target population .\n76Equity\n▪What would be the impact on health equity of recommending RSV \nvaccines in adults aged ≥65 years ?\nReduced\nProbably reduced\nProbably no impact\nProbably increased\nIncreased\nVaries\nDon’t know\n77Equity\n▪What would be the impact on health equity of recommending RSV \nvaccines in adults aged 60–64 years ?\nReduced\nProbably reduced\nProbably no impact\nProbably increased\nIncreased\nVaries\nDon’t know\nMinority opinion\nSummary\n79Domain Question Work Group Judgements\nAdults aged ≥65 years Pfizer GSK\nPublic Health \nProblemIs RSV of public health importance? Yes\nBenefits and \nHarmsHow substantial are the desirable anticipated effects? Moderate Moderate\nHow substantial are the undesirable anticipated effects? Small Small\nDo the desirable effects outweigh the undesirable effects? Favors intervention Favors intervention\nWhat is the overall certainty of the evidence profile? Moderate Moderate\nValuesDoes the target population feel the desirable effects are large \nrelative to the undesirable effects?Yes/Probably yes\nIs there important variability in how patients value the \noutcomes?Important variability/Probably important variability\nAcceptability Is the intervention acceptable to key stakeholders? Yes/Probably yes\nFeasibility Is the intervention feasible to implement? Yes/Probably yes Yes/Probably yes\nResource UseIs the intervention a reasonable and efficient allocation of \nresources?Probably yes Probably yes\nEquity What would be the impact on health equity? Probably increased/Probably no impact\n80Domain Question Work Group Judgements\nAdults aged 60–64 years Pfizer GSK\nPublic Health \nProblemIs RSV of public health importance? Yes\nBenefits and \nHarmsHow substantial are the desirable anticipated effects? Small –Moderate Small –Moderate\nHow substantial are the undesirable anticipated effects? Small Small\nDo the desirable effects outweigh the undesirable effects? Unclear Unclear\nWhat is the overall certainty of the evidence profile? Moderate Moderate\nValuesDoes the target population feel the desirable effects are large \nrelative to the undesirable effects?Yes/Probably yes\nIs there important variability in how patients value the \noutcomes?Important variability/Probably important variability\nAcceptability Is the intervention acceptable to key stakeholders? Yes/Probably yes\nFeasibility Is the intervention feasible to implement? Yes/Probably yes Yes/Probably yes\nResource UseIs the intervention a reasonable and efficient allocation of \nresources?Probably no Probably no\nEquity What would be the impact on health equity? Unclear\n81Work Group interpretation (part 1)\n▪Pfizer’s bivalent RSVpreF and GSK’s adjuvanted RSVPreF3 vaccines both \nhave demonstrated significant efficacy against lower respiratory tract \nillness caused by RSV among older adults over at least two seasons\n–Trials were underpowered to show efficacy in the oldest adults and in adults \nwho are frail\n–Trials were underpowered to show efficacy against RSV hospitalization\n•Efficacy against symptomatic illness may indicate efficacy against more \nsevere disease\n▪RSV vaccination has the potential to prevent considerable morbidity from \nRSV disease among older adults, particularly in those with chronic medical \nconditions and those who are frail (e.g., long -term care facility residents)\n82Work Group interpretation (part 2)\n▪Cases of inflammatory neurologic events have been reported within 42 \ndays after vaccination with each RSV vaccine\n▪Clinical trials were not sufficiently powered to determine whether the \nsmall number of cases occurred due to random chance\n▪Whether there is an increased risk of GBS or other inflammatory \nneurologic events from RSV vaccination is not known at this time\n▪Post -licensure surveillance for both safety and vaccine effectiveness will be \ncritical\n83Choice of age threshold at which to recommend RSV vaccines\nPros Cons\nAge ≥65 years \nonly•Greater risk of RSV disease and therefore \nmore favorable population -wide balance \nof risks and benefits of vaccination (in \nlight of cases of inflammatory neurologic \nevents observed)\n•Aligns with recommendations for high -\ndose and adjuvanted influenza vaccines, \nand universal pneumococcal vaccination•Lost opportunity to prevent additional disease \nin the 60 –64 age group, who are \ndisproportionately from racial and ethnic \ngroups impacted by RSV at earlier ages\nAlso in ages \n60–64 years•Potential to prevent a greater total \nburden of disease (e.g., number of \nhospitalizations)\n•Increases access to adults 60 –64 with \nmedical risk factors for severe RSV \ndisease (disproportionately in racial and \nethnic groups impacted by RSV at earlier \nages)•Risk/benefit balance depends on the patient \npopulation that seeks and receives vaccination \namong those 60 –64\n•Uninsured adults would face financial barriers \nobtaining vaccination (disproportionately aged \n60–64 in racial, ethnic and socioeconomic \ngroups at greater risk of severe RSV)\n•May experience more difficulty achieving \nclinician adoption of the recommendation \namong patients 60 –64\n•Less efficient allocation of societal resources\n84Evidence to Recommendations Framework\nSummary: Work Group Interpretations\n▪Work Group interpretations were similar for:\n–Pfizer bivalent RSVpreF\n–GSK adjuvanted RSVPreF3\n85Evidence to Recommendations Framework\nSummary: Work Group Interpretations (Pfizer RSVpreF , GSK RSVPreF3)\nBalance of \nconsequencesUndesirable \nconsequences \nclearly outweigh \ndesirable \nconsequences in \nmost settingsUndesirable \nconsequences \nprobably \noutweigh \ndesirable \nconsequences in \nmost settingsThe balance \nbetween \ndesirable and \nundesirable \nconsequences is \nclosely balanced \nor uncertainDesirable \nconsequences \nprobably \noutweigh \nundesirable \nconsequences in \nmost settingsDesirable \nconsequences \nclearly outweigh \nundesirable \nconsequences in \nmost settingsThere is \ninsufficient \nevidence to \ndetermine the \nbalance of \nconsequencesAmong adults aged ≥65 years :\nBalance of \nconsequencesUndesirable \nconsequences \nclearly outweigh \ndesirable \nconsequences in \nmost settingsUndesirable \nconsequences \nprobably \noutweigh \ndesirable \nconsequences in \nmost settingsThe balance \nbetween \ndesirable and \nundesirable \nconsequences is \nclosely balanced \nor uncertainDesirable \nconsequences \nprobably \noutweigh \nundesirable \nconsequences in \nmost settingsDesirable \nconsequences \nclearly outweigh \nundesirable \nconsequences in \nmost settingsThere is \ninsufficient \nevidence to \ndetermine the \nbalance of \nconsequencesAmong adults aged 60–64 years :Minority opinion\n86Evidence to Recommendations Framework\nSummary: Work Group Interpretations (Pfizer RSVpreF , GSK RSVPreF3)\nType of recommendation, adults aged ≥65 years\nWe do not recommend the intervention\nWe recommend the intervention for individuals based on shared clinical decision -making\nWe recommend the intervention\nMinority opinion\n87Evidence to Recommendations Framework\nSummary: Work Group Interpretations (Pfizer RSVpreF , GSK RSVPreF3)\nType of recommendation, adults aged ≥65 years\nWe do not recommend the intervention\nWe recommend the intervention for individuals based on shared clinical decision -making\nWe recommend the intervention\nType of recommendation, adults aged 60–64years\nWe do not recommend the intervention\nWe recommend the intervention for individuals based on shared clinical decision -making\nWe recommend the intervention\nMinority opinion\n88Proposed ACIP Voting Language\n•Adults 65 years of age and older are recommended to receive \na single dose of RSV vaccine.\n•Individual adults aged 60 –64 years may receive a single dose \nof RSV vaccine, using shared clinical decision -making based on \nrisk assessment.\n89Acknowledgements \n▪ Karen Broder\n▪ Doug Campos -Outcalt\n▪ Katherine Fleming -Dutra\n▪ Monica Godfrey\n▪ Fiona Havers\n▪ Anne Hause\n▪ Jefferson Jones\n▪ Andrew Leidner\n▪ Meredith McMorrow\n▪ Rebecca Morgan\n▪ Dani Moulia\n▪ Neil Murthy▪ Sara Oliver\n▪ Christine Olson\n▪ Ismael Ortega Sanchez\n▪ David Shay\n▪ Amanda Payne\n▪ Huong Pham\n▪ Jamison Pike\n▪ Mila Prill\n▪ Lauren Roper\n▪ Hannah Rosenblum\n▪ Jim Sejvar\n▪ Tom Shimabukuro▪ Evelyn Twentyman \n▪ Megan Wallace\n▪ Michael Whitaker\n▪ Patricia Wodi", "summary": "Centers for Disease Control and Prevention Evidence to Recommendations Framework Respiratory Syncytial Virus (RSV) in Adults Pfizer bivalent RSVpreF vaccine in older adults  GSK adjuvanted RSVPreF3 vaccine in older adults Michael Melgar, MD Amadea Britton, MD Advisory Committee on Immunization Practices June 21, 2023 2Evidence to Recommendations ( EtR) Framework Policy Questions ▪Should a single dose of Pfizer bivalent RSVpreF vaccine (120µg antigen, 1 dose IM),  rather than no vaccine, be…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/06-RSV-Adults-Melgar-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 89}
{"title": "07 RSV Adults Britton 508", "content": "Centers for Disease Control and Prevention\nSummary of Proposed Clinical Considerations for RSV \nVaccines\nJune 21, 2023\nACIP Older Adult RSV Vaccine Session\nAmadea Britton, MD\nMichael Melgar, MD\nOverview of clinical considerations\n▪Shared clinical decision -making based on risk assessment among \nadults aged 60 –64 years\n▪Timing of RSV vaccination for the 2023 –2024 RSV season\n▪Coadministration of RSV vaccines with other vaccines\n▪Persons with immunocompromising conditions\n2\nClinical consideration: Shared clinical decision -making \nbased on risk assessment among adults aged 60 –64 years\nThe decision about whether or not to vaccinate \nan individual may be informed by:\n•Best available evidence of who may \nbenefit\n•An individual’s characteristics, values, and \npreferences\n•Health care provider’s clinical discretion\n•Characteristics of the vaccine being \nconsidered\n3Source: CDC. ACIP Shared Clinical Decision -Making Recommendations. Website:  https://www.cdc.gov/vaccines/acip/acip -scdm -faqs.html . \nLast updated February 10, 2020. Accessed June 13, 2023. For shared clinical \ndecision -making \nrecommendations \nthere is no default.\nIf shared clinical decision -making is recommended adults who may \nbe at higher risk of RSV disease include persons with:\n4\nImmune \ncompromise\nEndocrine disorders \nsuch as diabetes\nHematologic \ndisorders\nChronic cardiovascular \ndiseases such as congestive \nheart failure and coronary \nartery disease\nResidents of nursing \nhomes and other long -\nterm care facilities\nNeurologic disorders\nChronic lung diseases \nsuch as COPD and \nasthma\nKidney and liver \ndisorders\nOther underlying conditions or \nfactors that the provider \ndetermines might increase the \nrisk of severe respiratory illness\nIf shared clinical decision -making is recommended adults who may \nbe at higher risk of RSV disease include persons with:\n5\nImmune \ncompromise\nEndocrine disorders \nsuch as diabetes\nHematologic \ndisorders\nChronic cardiovascular \ndiseases such as congestive \nheart failure and coronary \nartery disease\nResidents of nursing \nhomes and other long-\nterm care facilities\nNeurologic disorders\nChronic lung diseases \nsuch as COPD and \nasthma\nKidney and liver \ndisorders\nOther underlying conditions\nor factors that the provider \ndetermines might increase the \nrisk of severe respiratory illness\nClinical consideration: Timing of RSV vaccination for \nthe 2023 –2024 RSV season\n6RSV vaccination is currently approved and recommended as a \nsingle dose.\nOptimally, vaccination of eligible adults should occur before \nthe onset of increased RSV activity in the community. \nThe timing of the onset, peak, and decline of RSV activity \nvaries each year, and RSV seasonality during the COVID -19 \npandemic deviated from prior seasons.\n7RSV Hospitalizations in adults aged ≥65 years by season:\nRSV-NET 2017 –2023\nCOVID -19 pandemic affected RSV\nseasonality in 2020 -21, 2021 -22,\nand 2022 -23\nRSV-NET: unpublished data. Surveillance for 2017 -18 through 2019 -20 seasons were conducted from October –April; for 2020 -21 and 2021 -22 surveillance was conducted continuously from \nOctober –September. Data shown for 2022 -23 season is from October –December 2022. 050100150200250300\n40424446485052 2468101214161820222426283032343638Weekly RSV hospitalizations\nMMWR Week\n2017-18 2018-19 2019-20 2020-21 2021-22 2022-23January\nClinical consideration: Timing of RSV vaccination for \nthe 2023 –2024 RSV season\n8Given this \nvariability the \nideal time to start \nvaccinating \ncannot be \npredicted in \nadvance of the \n2023-2024 RSV \nseason.Providers should \ntherefore offer \nRSV vaccination \nas soon as \nvaccine supply \nbecomes \navailable.Providers should \ncontinue to offer \nRSV vaccination \nthroughout the \nRSV season to \neligible adults \nwho remain \nunvaccinated .There are \ninsufficient data \nat this time to \ndetermine the \nneed for \nrevaccination.\nClinical consideration: Coadministration of RSV \nvaccines with other vaccines\n9In accordance with General Best Practice Guidelines for \nImmunization, coadministration of RSV vaccines with other \nadult vaccines is acceptable.*\n*ACIP Timing and Spacing Guidelines for Immunization | CDCThis includes giving RSV vaccines simultaneously with \nseasonal influenza vaccines, COVID -19 vaccines, \npneumococcal vaccines, Td/Tdap, and recombinant zoster \nvaccine (Shingrix) .\nData on immunogenicity of coadministration of RSV \nvaccines with other vaccines\n•There are currently limited data available on immunogenicity of \ncoadministration of RSV vaccines and other vaccines.\n•In general, coadministration of RSV and seasonal influenza \nvaccines met non -inferiority criteria for immunogenicity.*\n•However, RSV and influenza antibody titers were generally \nsomewhat lower with coadministration.\n•Additional studies on immunogenicity of coadministration of RSV \nwith other adult vaccines are in process.\n10* Pre -specified non -inferiority criteria for immune responses were met across trials, with the exception of the FluA /Darwin H3N2 strain \nafter simultaneous administration of RSVPreF3 vaccine ( Arexvy by GSK) and adjuvanted quadrivalent inactivated influenza vaccine. \nReactogenicity and safety of coadministration of RSV \nvaccines with other vaccines\n•Coadministration of multiple vaccines at the same visit may increase reactogenicity.\n•Only coadministration of RSV and influenza vaccines have clinical trial data available. \nEvidence is mixed on whether there may be increased reactogenicity with \ncoadministration of RSV and influenza vaccines.\n•Data are lacking on coadministration of other vaccines that might be recommended \nfor people in this age group, such as COVID -19 vaccines, pneumococcal vaccines, \nTd/Tdap, and the recombinant zoster vaccine (Shingrix by GSK) which contains the \nsame adjuvant as RSVPreF3 vaccine ( Arexvy by GSK).\n•Post -licensure safety monitoring of coadministration of RSV vaccines with other \nvaccines will further inform coadministration guidance.\n11\nClinical consideration: RSV vaccines and persons with \nimmunocompromising conditions\n12Persons with \nimmunocompromising conditions \nare recommended to receive the \nRSV vaccine under shared clinical \ndecision -making given the \npotential for significant benefit.Adults with immunocompromising \nconditions are at risk of severe RSV -\nassociated disease and death.\nThey may benefit from RSV vaccination \nbut were not included in the clinical \ntrials so efficacy in this population is \nunknown.\nThese individuals, including those \nreceiving immunosuppressive therapy, \nmay have a diminished immune \nresponse to RSV vaccination.\nFor more information, contact CDC\n1-800-CDC-INFO (232- 4636)\nTTY:  1- 888- 232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the \nofficial position of the Centers for Disease Control and Prevention.\nAcknowledgements: \nMichael Melgar\nLauren Roper\nHannah Rosenblum\nMelinda Wharton\nTara Anderson \nLisa Grohskopf\nDavid ShayTom Shimabukuro\nKaren Broder\nMila Prill\nAnne Hause\nFiona Havers\nMeredith McMorrow\nJefferson Jones\nKatherine Fleming -DutraAndrew Kroger\nManisha Patel\nSarah Meyer \nNeil Murthy\nPatricia Wodi\nSara Oliver", "summary": "Centers for Disease Control and Prevention Summary of Proposed Clinical Considerations for RSV  Vaccines June 21, 2023 ACIP Older Adult RSV Vaccine Session Amadea Britton, MD Michael Melgar, MD Overview of clinical considerations ▪Shared clinical decision -making based on risk assessment among  adults aged 60 –64 years ▪Timing of RSV vaccination for the 2023 –2024 RSV season ▪Coadministration of RSV vaccines with other vaccines ▪Persons with immunocompromising conditions 2 Clinical…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/07-RSV-Adults-Britton-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 13}
{"title": "01 POLIO Brooks 508", "content": "CenCenCen Centt tterer erers fs f s fs for Disease Coor Disease Coor Disease Coor Disease Co nn nntrtrtr trol ol ol ol andandandand    PrPr PrPree eevv vvenen enentiti tition ononon\nNaNaNaNational Cen tional Centional Centional Cent ttter f er fer fer for or or or ImIm ImImmunizmuniz munizmuniz aa aation antion an tion antion an d Rd Rd Rd Respiespi espiespir rrra aaattttoror orory y y y DiseDiseDiseDise ases asesasesases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.ACIP Polio Vaccination Work Group\nOliver Brooks, MD, FAAP\nACIP Meeting\nJune 21, 2023\n\n1)Whether more specific guidance on adult vaccination , including use of adult \nbooster doses, can be provided in the context of circulating poliovirus.\n2)Whether adults who are immunocompromised should be recommended an \nadditional adult booster of a polio -containing vaccine.\n3)Whether fractional doses of IPV ( fIPV ), as prequalified by WHO, should m eet polio\nvaccination requirements, including for people immigrating to the United States .\n4)Consider criteria under which novel Oral Polio Vaccine type 2 (nOPV2) might be \nused in areas with outbreaks or persistent circulation of poliovirus.Polio Vaccination Work Group Terms of Reference\nPolicy topics under consideration:", "summary": "CenCenCen Centt tterer erers fs f s fs for Disease Coor Disease Coor Disease Coor Disease Co nn nntrtrtr trol ol ol ol andandandand    PrPr PrPree eevv vvenen enentiti tition ononon NaNaNaNational Cen tional Centional Centional Cent ttter f er fer fer for or or or ImIm ImImmunizmuniz munizmuniz aa aation antion an tion antion an d Rd Rd Rd Respiespi espiespir rrra aaattttoror orory y y y DiseDiseDiseDise ases asesasesases Photographs and images included in this presentation are licensed solely…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/01-POLIO-Brooks-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 2}
{"title": "02 POLIO Kidd Jun 2023", "content": "Centers for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.Adult Polio Vaccination\nSarah Kidd, MD, MPH\nACIP Meeting\nJune 21, 2023\n\n▪Summarize work group deliberations on adult polio vaccination\n–Recommendations for unvaccinated and incompletely vaccinated adults\n–Recommendations for booster doses of IPV\n▪Present work group’s proposed language for an ACIP voteObjectives for Today’s Presentation \n▪Problem\n–Is the problem of public health importance?\n▪Benefits & Harms\n–How substantial are the desirable anticipated effects?\n–How substantial are the undesirable anticipated effects?\n–Do the desirable effects outweigh the undesirable effects?\n–What is the overall certainty of this evidence for the critical outcomes?\n▪Values\n–Does the target population feel that the desirable effects are large relative to the undesirable effects?\n–Is there important uncertainty about or variability in how much people value the main outcome?\n▪Acceptability\n–Is the intervention acceptable to key stakeholders?\n▪Resource Use\n–Is the intervention a reasonable and efficient allocation of resources?\n▪Equity\n–What would be the impact on health equity?\n▪Feasibility\n–Is the intervention feasible to implement?ACIP Evidence to Recommendations ( EtR) Framework\n▪Vaccination is recommended for certain adults who are at greater risk for exposure \nto polioviruses than the general population\n▪Unvaccinated adults who are at increased risk of exposure should receive a primary \nvaccination series with IPV\n▪Adults who have had a primary series of oral polio vaccine (OPV) or IPV and who \nare at increased risk of exposure can receive another dose of IPV2000 Recommendations for Inactivated Polio Vaccine (IPV) \nVaccination of Adults\nPoliomyelitis Prevention in the United States (cdc.gov)\n▪2000 statement focused on adults at increased risk of poliovirus exposure\n▪Uncertainty about how to define increased risk in setting of circulating vaccine -\nderived poliovirus ( cVDPV ) in US\n▪Unclear guidance for unvaccinated adults who were notknown to be at increased \nrisk of exposure\n▪Uncertainty about vaccinated adults and when/if a booster was advised2000 Statement on IPV Vaccination for Adults\nQuestions that arose in 2022\nPoliomyelitis Prevention in the United States (cdc.gov)\nIPV = inactivated polio vaccine\ntOPV = trivalent oral polio vaccine▪Should completion of a primary polio vaccination series with IPV be recommended \nfor unvaccinated and incompletely vaccinated adults in the US?\n–Population: Unvaccinated and incompletely vaccinated (with tOPV or IPV) US adults aged ≥18 years\n–Intervention: Completion of a primary vaccination series with IPV\n–Comparison: No vaccination or partial series completion\n–Outcomes: \n•Prevention of paralytic poliomyelitis\n•Serologic immunity to poliovirus types 1, 2, and 3\n•Serious adverse events following vaccination\n•Indirect effects, e.g., community transmission, impact on health systemsPolicy Question #1 for Work Group\n▪A primary series of ≥3 doses of tOPV or IPV in any combination administered ≥4 \nweeks apart\nAND\n▪The last dose in the series was given on or after the 4thbirthday\nAND\n▪The last dose in the series was given ≥6 months after the previous doseCurrent Definition of Fully Vaccinated\nUpdated Recommendations of the Advisory Committee on Immunization Practices (ACIP) Regarding Routine Poliovirus Vaccination \n(cdc.gov) ; Poliomyelitis Prevention in the United States (cdc.gov)\n▪Poliovirus infection can cause \npoliomyelitis and lifelong paralysis\n–Paralytic disease occurs in <1% of \ninfections (varies by serotype)\n–Non-paralytic clinical illness occurs in \n~25%, including 1% –5% with aseptic \nmeningitis\n–Approximately 75% of infections are \nasymptomaticPublic Health Problem\n\nParalytic polio decreased rapidly in the US after \nintroduction of polio vaccine\n0500010000150002000025000\n1950\n1952\n1954\n1956\n1958\n1960\n1962\n1964\n1966\n1968\n1970\n1972\n1974\n1976\n1978\n1980\n1982\n1984\n1986\n1988\n1990\n1992\n1994\n1996\n1998\n2000\n2002\n2004\n2006\n2008\n2010\n2012\n2014\n2016\n2018\n20201994: Americas \ncertified polio -free\nYearNumber of poliomyelitis cases1955: Salk IPV\n1961: Sabin OPV1979: Last indigenous \nWild -type case in US\n2000: IPV only1997 : Sequential enhanced -potency\nIPV followed by OPV\nGlobal Paralytic WPV1 and cVDPV Cases1, Previous 12 Months2\nPolio Now –GPEI (polioeradication.org) WPV1 = wild poliovirus type 1; cVDPV = circulating vaccine -derived poliovirus\n\nParalytic Polio Case in New York State, July 2022\n•A case of paralytic polio caused by vaccine -derived poliovirus type 2 (VDPV2) was \nconfirmed in an unvaccinated young adult from Rockland County, New York, on \nJuly 21, 2022\n•Genetic sequencing has indicated a linkage to polioviruses collected in \nwastewater in Israel, United Kingdom, and Canada\n•Rockland County has reported overall low vaccine coverage for over 20 years\n•In summer 2022, 60% of children under 2 years of age had received 3 doses of \nIPV (zip code level as low as 37%)\n•No additional paralytic cases have been identified\nWWS Report (ny.gov)▪Poliovirus type 2 genetically linked to the case detected \nin wastewater samples in New York (Rockland, Orange, \nSullivan, and Nassau counties and New York City)\n▪Retrospective testing detected poliovirus as early as \nApril 2022\n▪Only 2 positive samples since November 1st(December \n15thin Orange; February 22ndin Rockland)\n▪No detections in samples collected in last 15 weeksWastewater Testing for Poliovirus in New York\n\nPoliovirus in New York, 2022\nSource: Polio WWS Report (ny.gov)▪One paralytic polio \ncase in unvaccinated \nyoung adult in \nRockland County, NY \nin 2022\n▪Likely indicative of  \n≥1–2 thousand   \nmostly asymptomatic \ninfections\n\nNational Salk Vaccination Coverage by September 1961 by Age and Race, \nHousehold US Immunization Survey (USIS)\nSource: Morris, Public Health Reports 1964.Number of doses (%)\nBirth year Age in 1961 0 1–2 ≥3\n1957 –1960 1–4 years\nWhite 11% 11% 78%\nNon -white 26% 21% 53%\n1952 –1956 5–9 years\nWhite 6% 5% 89%\nNon -white 13% 16% 72%\n1947 –1951 10–14 years\nWhite 6% 5% 89%\nNon -white 12% 12% 77%\n1942 –1946 15–19 years\nWhite 14% 7% 78%\nNon -white 25% 11% 64%\nNational Salk Vaccination Coverage by September 1961 by Age and Race, \nHousehold US Immunization Survey (USIS)\nSource: Morris, Public Health Reports 1964.Number of doses (%)\nBirth year Age in 1961 0 1–2 ≥3\n1932 –1941 20–29 years\nWhite 34% 11% 55%\nNon -white 55% 12% 33%\n1922 –1931 30–39 years\nWhite 43% 10% 48%\nNon -white 65% 11% 24%\n1912 –1921 40–49 years\nWhite 70% 6% 24%\nNon -white 83% 6% 11%\n1902 –1911 50–59 years\nWhite 90% 3% 8%\nNon -white 92% 4% 4%\n0102030405060708090100Polio3 Coverage (%)\nYear of SurveyNational Surveys of 3 -dose Polio (Polio3) Vaccination \nCoverage among Children, United States, 1959 –2017 \nSources: Simpson et al, AJPM 2001 Forty years and four surveys: How does our measuring measure up? –ScienceDirect . CDC, MMWR 2001 National, State, and Urban Area Vaccination Coverage Levels Among \nChildren Aged 19 --35 Months ---United States, 2000 (cdc.gov) . CDC, MMWR 2006 National, State, and Urban Area Vaccination Coverage Among Children Aged 19 --35 Months ---United States, 2005 (cdc.gov) . \nCDC, MMWR 2011 National and State Vaccination Coverage Among Children Aged 19 --35 Months ---United States, 2010 (cdc.gov) . Hill et al, MMWR 2016 Vaccination Coverage Among Children Aged 19 –35 \nMonths —United States, 2015 | MMWR (cdc.gov) . Hill et al, MMWR 2018 Vaccination Coverage Among Children Aged 19 –35 Months —United States, 2017 | MMWR (cdc.gov) .USIS -reported Polio3 coverage among \nchildren aged 1 –4 years\nNHIS -reported Polio3 coverage among \nchildren aged 24 –35 monthsNIS-reported Polio3 coverage among \nchildren aged 19 –35 months\nPercent positive (95% Confidence Interval)\nBirth years Age in 2009 –2010 Poliovirus Type 1 Poliovirus Type 2 Poliovirus Type 3\n1998 –2004 6–11 years 97.2 (94.7 –98.8) 98.0 (96.4 –99.0) 93.8 (91.8 –95.4)\n1990 –1998 12–19 years 94.7 (92.0 –96.6) 98.2 (96.6 –99.2) 84.3 (81.0 –87.2)\n1970 –1990 20–39 years 92.7 (90.0 –94.2) 96.9 (95.2 –98.2) 78.6 (74.6 –82.2)\n1960 –1970 40–49 years 93.9 (91.6 –95.7) 95.8 (93.8 –97.3) 85.8 (82.3 –88.8)Seroprevalence of Poliovirus Antibodies by Age, \nUnited States NHANES Serosurvey, 2009 –2010\nSource: Wallace et al, BMC Public Health 2016.\nPercent positive (95% Confidence Interval)\nBirth years Age & Race/Ethnicity Poliovirus Type 1 Poliovirus Type 2 Poliovirus Type 3\n1998 –2004 6–11 years\nMexican -American 98.5 (96.4 –99.5) 98.2 (96.0 –99.4) 97.7 (94.7 –99.3)\nOther Hispanic 98.8 (93.5 –100.0) 99.2 (94.7 –100.0) 93.8 (87.0 –97.7)\nNon -Hispanic White 96.9 (93.1 –98.9) 97.6 (94.9 –99.1) 92.3 (88.5 –95.2)\nNon -Hispanic Black 99.1 (96.0 –99.9) 99.1 (96.3 –99.9) 96.1 (90.6 –98.8)\nNon -Hispanic Other 92.8 (83.1 –97.9) 97.6 (87.6 –99.9) 91.1 (81.0 –96.9)\n1990 –1998 12–19 years\nMexican -American 93.7 (90.5 –96.1) 98.4 (96.3 –99.4) 80.4 (74.5 –85.4)\nOther Hispanic 96.1 (90.2 –98.9) 99.1 (94.7 –100.0) 88.5 (81.0 –93.8)\nNon -Hispanic White 94.7 (89.5 –97.8) 97.7 (95.1 –99.2) 84.3 (79.3 –88.5)\nNon -Hispanic Black 93.8 (89.4 –96.7) 99.6 (97.7 –100.0) 84.6 (79.3 –89.0)\nNon -Hispanic Other 97.1 (90.7 –99.6) 98.6 (93.0 –100.0) 88.5 (79.3 –94.6)Seroprevalence of Poliovirus Antibodies by Age & Race/Ethnicity, \nUnited States NHANES Serosurvey, 2009 –2010\nSource: Wallace et al, BMC Public Health 2016.\nBirth years Age & Race/EthnicityPercent positive (95% Confidence Interval)\nPoliovirus Type 1 Poliovirus Type 2 Poliovirus Type 3\n1970 –1990 20–39 years\nMexican -American 91.2 (86.1 –94.9) 93.7 (90.2 –96.2) 76.2 (71.5 –80.4)\nOther Hispanic 86.7 (78.5 –92.6) 94.2 (89.8 –97.1) 78.4 (70.5 –84.9)\nNon -Hispanic White 93.6 (91.2 –95.5) 97.2 (95.3 –98.5) 79.2 (75.1 –82.9)\nNon -Hispanic Black 94.7 (91.5 –96.9) 98.4 (96.4 –99.5) 81.6 (75.8 –86.6)\nNon -Hispanic Other 90.5 (82.4 –95.8) 98.9 (92.4 –100.0) 74.3 (54.9 –88.6)\n1960 –1970 40–49 years\nMexican -American 89.1 (83.9 –93.1) 88.7 (80.9 –94.1) 75.8 (69.5 –81.3)\nOther Hispanic 89.4 (81.6 –94.7) 91.3 (82.4 –96.7) 85.4 (72.5 –93.8)\nNon -Hispanic White 94.9 (91.7 –97.1) 97.0 (94.3 –98.6) 87.0 (82.1 –91.0)\nNon -Hispanic Black 94.7 (90.0 –97.6) 96.9 (92.1 –99.2) 87.3 (78.7 –93.8)\nNon -Hispanic Other 92.9 (75.0 –99.2) 96.1 (87.2 –99.5) 86.2 (68.9 –95.9)Seroprevalence of Poliovirus Antibodies by Age & Race/Ethnicity, \nUnited States NHANES Serosurvey, 2009 –2010\nSource: Wallace et al, BMC Public Health 2016.\n▪US remains at risk of poliovirus importations as long as there is ongoing transmission \nof poliovirus globally\n▪Data indicate that most US adults have serologic immunity to poliovirus types 1 –3\n▪However, unvaccinated and incompletely vaccinated adults remain susceptible to \nparalytic polio if exposed to poliovirusSummary of Problem\nWork group interpretation\nIs paralytic poliomyelitis a problem of public health importance?EtRDomain: Public Health Problem\nNoProbably \nnoProbably \nyesYes VariesDon’t \nknow\n▪Presence of detectable neutralizing antibody is a correlate of protection against \nparalytic disease.\n–Immunity against paralytic disease may be present even in absence of detectable antibodies.\n▪Serologic immunogenicity among infants and children\n–70% –100% seropositive after 2 doses\n–88% –100% seropositive after 3 doses\n▪Estimates of vaccine effectiveness against paralytic polio\n–36% –89% for 1 dose\n–89% –98% for 2 doses\n▪Paucity of data on adults receiving a primary seriesEffectiveness of Enhanced -Potency IPV\nSources: Vidor et al review, PIDJ 1997. Stoeckel et al, Rev Infect Dis 1984. CDC, MMWR 1988. John, Rev Med Virol 1993.\n▪Intestinal immunity\n–No significant difference between IPV and unvaccinated individuals in the odds of shedding \n–IPV vaccination appears to reduce the mean quantity of shed poliovirus by 63% –91%\n–Some data to suggest that IPV vaccination reduces duration of shedding ; recent modeling study \nindicated no impact of IPV\n▪Nasopharyngeal (NP) immunity\n–Evidence to suggest similar, low rates of NP shedding (0% –4%) among OPV and IPV vaccineesIPV and Mucosal Immunity\nSources: Hird and Grassly meta -analysis, PLoS Pathogens 2012. Kok et al, Bulletin of WHO 1992. Onorato et al, JID 1991. Brouwer et al, J R Soc Interface 2022.\n▪Local reactions at injection site reported in trials\n–Tenderness in 14% –29%\n–Induration in 3% –11%\n–Erythema in 0.5% –1.4%\n▪Combining IPV with other vaccines is not associated with increased frequency or \nseverity of reported adverse reactions compared with the other vaccines alone\n▪No severe adverse events have been causally associated with use of the current \nformulation of IPVSafety\nSources: Sanofi Pasteur Package Insert -IPOL (fda.gov) . Vidor et al, PIDJ 1997. Murdin et al, Vaccine 1996. Wattigney et al, Pediatrics 2001. IOM 1994. \n▪>250 million IPV -containing vaccine doses distributed 2000 –2012\n▪41,792 adverse event reports submitted for IPV -containing vaccines\n–34,880 (88%) were for non -serious events \n–95% were among persons <7 years of age\n▪Most events were associated with IPV co -administered with other vaccines\n▪Standalone IPV accounted for just 0.5% of reports\n▪VAERS is passive reporting system, cannot assess causal associationsVaccine Adverse Event Reporting System (VAERS) Data, \n2000 –2012\nSource: Iqbal et al, Lancet ID 2015. \nWork group interpretation\nHow substantial are the desirable anticipated effects of completing a \nprimary polio vaccination series in unvaccinated adults?EtRDomain: Benefits & Harms\nMinimal Small Moderate Large VariesDon’t \nknow\nWork group interpretation\nHow substantial are the undesirable anticipated effects of completing a \nprimary polio vaccination series in unvaccinated adults?EtRDomain: Benefits & Harms\nMinimal Small Moderate Large VariesDon’t \nknow\nWork group interpretation\nDo the desirable effects of completing a primary polio vaccination series \noutweigh the undesirable effects in unvaccinated adults?EtRDomain: Benefits & Harms\nAnticipated \nbenefits \noutweigh \nanticipated \nharmsAnticipated \nharms outweigh \nanticipated \nbenefitsVaries Don’t know\nPublic Knowledge and Beliefs about Poliovirus\nAnnenberg Science Knowledge (ASK) Survey*, October 2022\n*Nationally representative panel of 1,572 US adults surveyed by SSRS for the Annenberg Public Policy Center of the University ofPennsylvania from October 11 -18, 2022; this \nwas 9thwave of the ASK survey whose respondents were first empaneled in April 2021.\nWhat U.S. Adults Know and Believe About Polio and the Bivalent Covid Booster | The Annenberg Public Policy Center of the Univ ersity of Pennsylvania\n▪85% said they were likely \nto recommend that an \neligible person in their \nhousehold get \nvaccinated with the polio \nvaccine \n▪Values of unvaccinated adults might differ from those of general population\n▪Unvaccinated adults are likely a heterogeneous group\n–Persons whose families chose for them to not be vaccinated as children\n–Persons who missed opportunities to be vaccinated as children\n▪Lack of data on how these populations perceive their risk of polio and perceive the \npotential positive vs. negative effects of polio vaccination Considerations for Values of Population in Question \n(Unvaccinated or Incompletely Vaccinated Adults)\nPros\n▪Context of global polio eradication efforts\n▪Prevention of paralytic polio has been a public health priority for decades\nCons\n▪Competing priorities for clinicians and local public health departments\n▪Uncertainty about eligibility for vaccination and true level of risk to adults in the US \noutside of outbreak settingAdditional Considerations for Acceptability to Key \nStakeholders\nWork group interpretation\nDoes the target population (unvaccinated or incompletely vaccinated \nadults) feel that the desirable effects of vaccination are large relative to \nundesirable effects?EtRDomain: Values of Target Population \nNoProbably \nnoProbably \nyesYes VariesDon’t \nknow\nWork group interpretation\nIs there important uncertainty or variability in how much people value \nthe main outcome (prevention of paralytic poliomyelitis)?EtRDomain: Values of Target Population \nImportant \nuncertainty \nor variabilityProbably \nimportant \nuncertainty \nor variabilityProbably not \nimportant \nuncertainty \nor variabilityNo \nimportant \nuncertainty \nor variabilityNo known \nundesirable \noutcomes\nWork group interpretation\nIs the intervention (vaccination of adults known or suspected to be \nunvaccinated or incompletely vaccinated) acceptable to key \nstakeholders?EtRDomain: Acceptability to Key Stakeholders\nNoProbably \nnoProbably \nyesYes VariesDon’t \nknow\nPotential supply:\n▪Currently just one US -licensed manufacturer of stand -alone IPV (Sanofi)\n▪Three US -licensed manufacturers of combination vaccines that include IPV (Sanofi, \nMerck, GSK)\nPotential demand: \n▪Difficult to quantify: Uncertain number of adults who know they are unvaccinated or \nundervaccinatedResource Use and Feasibility: Potential Supply and Demand\n▪Paralytic polio case identified in July 2022\n▪Persistent wastewater detections in area during summer to early fall 2022\n▪National and local media attention\n▪Calls for unvaccinated to get vaccinated\n▪Concerted health department efforts to reach unvaccinated persons\n▪No significant supply issuesResource Use and Feasibility: New York Experience \n▪Access to vaccination sites that stock IPV\n▪Potential effects on health system screening and recall algorithms\n–Will need clear guidance for who is eligible for vaccination\n▪Feasibility of implementing risk -based recommendations, particularly if risk of \nexposure in the population changes over timeAdditional Resource and Feasibility Considerations\nWork group interpretation\nIs the intervention (vaccination of adults known or suspected to be \nunvaccinated or incompletely vaccinated) a reasonable and efficient \nallocation of resources?EtRDomain: Resource Use \nNoProbably \nnoProbably \nyesYes VariesDon’t \nknow\nWork group interpretation\nIs the intervention (vaccination of adults known or suspected to be \nunvaccinated or incompletely vaccinated) feasible to implement?EtRDomain: Feasibility\nNoProbably \nnoProbably \nyesYes VariesDon’t \nknow\n▪Different rates of childhood vaccination and poliovirus immunity\n▪Opportunity to receive catch -up polio vaccination as an adult likely increases equity\n▪No known differences in vaccine effectiveness among immunocompetent persons in \nthe US setting\n▪Assuring equitable access to vaccination sites with IPV will be an important \nconsideration for implementation Equity Considerations\nWork group interpretation\nWhat would be the impact (of vaccinating adults known or suspected to \nbe unvaccinated or incompletely vaccinated) on health equity?EtRDomain: Equity\nReduced \nequityProbably \nreduced\nequityProbably \nno impactProbably \nincreased \nequityIncreased \nequityVariesDon’t \nknow\nFor unvaccinated/incompletely vaccinated adults known to be at increased risk of \npoliovirus exposure:Work Group Judgement: Balance of Consequences\nCompleting a Primary Polio Vaccination Series\nUndesirable\nconsequences \nclearly\noutweigh \ndesirable \nconsequences \nin most settingsUndesirable\nconsequences \nprobably \noutweigh\ndesirable \nconsequences \nin most settingsThe balance \nbetween \ndesirable and \nundesirable \nconsequences \nis closely \nbalanced or \nuncertainDesirable\nconsequences \nprobably\noutweigh \nundesirable \nconsequences \nin most settingsDesirable \nconsequences \nclearly \noutweigh \nundesirable \nconsequences \nin most \nsettingsThere is \ninsufficient \nevidence to \ndetermine the \nbalance of \nconsequences\nFor unvaccinated/incompletely vaccinated adults NOT specifically known to be at \nincreased risk of poliovirus exposure :Work Group Judgement: Balance of Consequences\nCompleting a Primary Polio Vaccination Series\nUndesirable\nconsequences \nclearly\noutweigh \ndesirable \nconsequences \nin most settingsUndesirable\nconsequences \nprobably \noutweigh\ndesirable \nconsequences \nin most settingsThe balance \nbetween \ndesirable and \nundesirable \nconsequences \nis closely \nbalanced or \nuncertainDesirable \nconsequences \nprobably \noutweigh \nundesirable \nconsequences \nin most \nsettingsDesirable\nconsequences \nclearly\noutweigh \nundesirable \nconsequences \nin most settingsThere is \ninsufficient \nevidence to \ndetermine the \nbalance of \nconsequences\nSituations that put adults at increased risk of exposure \nto poliovirus include:\n▪Travelers who are going to countries where polio is epidemic or \nendemic (For additional information, see Polio: For Travelers).\n▪Laboratory and healthcare workers who handle specimens that \nmight contain polioviruses.\n▪Healthcare workers or other caregivers who have close contact \nwith a person who could be infected with poliovirus.\n▪Unvaccinated or incompletely vaccinated adults whose children \nwill be receiving oral poliovirus vaccine (for example, international \nadoptees or refugees).\n▪Unvaccinated or incompletely vaccinated adults living or working \nin a community where poliovirus is circulating.Considerations for a Risk -Based vs. Uniform \nRecommendation for All Unvaccinated Adults\nSituations that put adults at increased risk of exposure \nto poliovirus include:\n▪Travelers who are going to countries where polio is epidemic or \nendemic (For additional information, see Polio: For Travelers).\n▪Laboratory and healthcare workers who handle specimens that \nmight contain polioviruses.\n▪Healthcare workers or other caregivers who have close contact \nwith a person who could be infected with poliovirus.\n▪Unvaccinated or incompletely vaccinated adults whose children \nwill be receiving oral poliovirus vaccine (for example, international \nadoptees or refugees).\n▪Unvaccinated or incompletely vaccinated adults living or working \nin a community where poliovirus is circulating.Considerations for a Risk -Based vs. Uniform \nRecommendation for All Unvaccinated Adults\n•Individual -level;\n•Opportunity to \nanticipate risk and \nvaccinate prior to \npotential exposure \nSituations that put adults at increased risk of exposure \nto poliovirus include:\n▪Travelers who are going to countries where polio is epidemic or \nendemic (For additional information, see Polio: For Travelers).\n▪Laboratory and healthcare workers who handle specimens that \nmight contain polioviruses.\n▪Healthcare workers or other caregivers who have close contact \nwith a person who could be infected with poliovirus.\n▪Unvaccinated or incompletely vaccinated adults whose children \nwill be receiving oral poliovirus vaccine (for example, international \nadoptees or refugees).\n▪Unvaccinated or incompletely vaccinated adults living or working \nin a community where poliovirus is circulating.Considerations for a Risk -Based vs. Uniform \nRecommendation for All Unvaccinated Adults\n•Population -level;\n•Group already at \nincreased risk at \ntime risk is \nrecognized;\n•Potential missed \nopportunities for \nvaccination prior to \nexposure\nChallenges in 2022:\n•In which of these \ncounties are \nunvaccinated adults \nconsidered at increased \nrisk of exposure?\n•When are unvaccinated \nadults in these counties \nno longer at increased \nrisk of exposure?\n•Are unvaccinated adults \ntraveling to these \ncounties at increased \nrisk of exposure?\nWWS Report_6_19_23 (ny.gov)\n\nPros:\n▪Allows unvaccinated adults and their health care providers to take advantage of \nopportunities to get vaccinated before they are at increased risk of exposure\n▪Brings adult polio vaccination policy closer in line with other routine childhood \nvaccines, e.g., MMR and varicella vaccines\n▪Is less complicated policy to communicate and understand (i.e., recommendation \ndoesn’t change based on latest wastewater data)Pros and Cons of a Uniform Recommendation for \nUnvaccinated and Incompletely Vaccinated Adults\nCons:\n▪Most adults in the United States have a low risk of poliovirus exposure and paralytic \npolio, and most adults received primary polio vaccination series as children\n▪Demand for IPV could potentially exceed supply, particularly if a large number of \nadults without documentation of polio vaccination status assume they were not \nvaccinated\n–However, this issue can be mitigated by providing guidance for this group in the clinical \nconsiderationsPros and Cons of a Uniform Recommendation for \nUnvaccinated and Incompletely Vaccinated Adults\n▪Majority of work group believe pros of uniform recommendation outweigh cons; \napproximately 1/3 favor current risk -based recommendation (and adding language \nfor those not known to be at increased risk of exposure)\nProposed Language :\nAdults who are known or suspected to be unvaccinated or incompletely vaccinated \nagainst polio should complete a primary vaccination series with IPV.Proposed Language for Unvaccinated and Incompletely \nVaccinated Adults\n▪In general, unless there are specific reasons to believe they were not vaccinated, \nmost adults who were born and raised in the United States can assume they were \nvaccinated against polio as children. Polio vaccination has been part of the routine \nchildhood immunization schedule for decades and is still part of the routine \nchildhood immunization schedule. Adults who received any childhood vaccines \nalmost certainly were vaccinated for polio.Important Context to Be Included in Clinical Considerations\n2ndPolicy Question: Adult IPV Boosters\n▪Should a booster IPV dose be recommended for adults at increased risk of \npoliovirus exposure who have previously completed a primary polio vaccination \nseries?\n–Population: US adults aged ≥18 years at increased risk of poliovirus exposure who have completed \na primary polio vaccination series (with tOPV , IPV, or a combination of both)\n–Intervention: Booster dose of IPV\n–Comparison: Adults who completed a primary series but did not receive a booster dose\n–Outcomes: \n•Prevention of paralytic poliomyelitis\n•Serologic immunity to poliovirus types 1, 2, and 3\n•Serious adverse events following vaccination\n•Indirect effects, e.g., community transmission, impact on health systemsPolicy Question #2 for Work Group\n▪2000 Statement: “ Adults who have had a primary series of OPV or IPV and who are \nat increased risk [of exposure to poliovirus] can receive another dose of IPV. \nAvailable data do not indicate the need for more than a single lifetime booster \ndose with IPV for adults .”\n▪Rationale\n–Longstanding recommendation since tOPV was used in routine immunization\n–Actual need for supplementary dose not established, but “there is value in assuring protection \nagainst infection with wild polioviruses when exposure can reasonably be expected.” (1977 ACIP \nStatement)\n–At least 2 reported cases of paralytic polio in adult travelers who had completed a primary \nvaccination series with Salk IPV and/or tOPVBoosters: 2000 Statement and Rationale\nCDC MMWR 1977; CDC MMWR 1986.\n▪IHR Emergency Committee recommendation for travelers DEPARTING countries with \npoliovirus circulation, to prevent exportation\n–Applies to residents and travelers staying >4 weeks\n–If implemented by a country, proof of polio vaccination (IPV or tOPV ) within the last 12 months could be \nrequired prior to leaving the country\n–Still included in most recent Polio IHR Statement\n▪2014 MMWR: \n“Adults who have completed a routine series of polio vaccine are considered to have lifelong \nimmunity to poliovirus but data are lacking. As a precaution, persons aged ≥18 years who are \ntraveling to areas where there has been WPV circulation in the last 12 months and who have \nreceived a routine series with either IPV or OPV in childhood should receive another dose of IPV \nbefore departure. For adults, available data do not indicate the need for more than a single lifetime \nbooster dose with IPV.”2014 Interim Guidance\nIn Response to WHO Polio International Health Regulations (IHR) Emergency Committee Temporary \nRecommendations\nWallace MMWR 2014; Statement of the thirty -fifth Polio IHR Emergency Committee (who.int)\nPercent positive (95% Confidence Interval)\nBirth years Age in 2009 –2010 Poliovirus Type 1 Poliovirus Type 2 Poliovirus Type 3\n1998 –2004 6–11 years 97.2 (94.7 –98.8) 98.0 (96.4 –99.0) 93.8 (91.8 –95.4)\n1990 –1998 12–19 years 94.7 (92.0 –96.6) 98.2 (96.6 –99.2) 84.3 (81.0 –87.2)\n1970 –1990 20–39 years 92.7 (90.0 –94.2) 96.9 (95.2 –98.2) 78.6 (74.6 –82.2)\n1960 –1970 40–49 years 93.9 (91.6 –95.7) 95.8 (93.8 –97.3) 85.8 (82.3 –88.8)Unclear Need for IPV Booster in Vaccinated Adults:\nSeroprevalence of Poliovirus Antibodies by Age, United States \nNHANES Serosurvey, 2009 –2010\nSource: Wallace et al, BMC Public Health 2016.NOTE: Presence of detectable neutralizing antibody is a correlate of protection against paralytic disease.\nImmunity against paralytic disease may be present even in absence of detectable antibodies.\n▪No data on vaccine effectiveness of primary \nseries + booster vs. primary series only\n▪Serologic studies in adults with heterogeneous \npre-booster vaccination \nhistories/seropositivity: 98% –100% were \nseropositive 1 month after an IPV -containing \nbooster\n▪One study followed up trial participants 10 \nyears post -booster: 98% –100% still seropositiveBenefits of IPV Booster\nSources: Broderick et al, Vaccine 2015; Domenicus et al, Vaccine 2014; Fukushima et al, Vaccines 2022; Grimprel et al, Vaccine 2005; Kovac et al, Vaccine 2015; Larnaudie et al, \nHuman Vaccines 2010; Zimmermann et al, Vaccine 2013.Data from Grimprel et al, Vaccine 2005: \nSeropositivity before and 1 month after IPV-\ncontaining booster by study group and \npoliovirus serotype\n\n▪Local reactions at injection site reported in trials\n–Tenderness in 14% –29%\n–Induration in 3% –11%\n–Erythema in 0.5% –1.4%\n▪Combining IPV with other vaccines is not associated with increased frequency or \nseverity of reported adverse reactions compared with the other vaccines alone\n▪No severe adverse events have been causally associated with use of the current \nformulation of IPVSafety of IPV\nSources: Sanofi Pasteur Package Insert -IPOL (fda.gov)  . Vidor et al, PIDJ 1997. Murdin et al, Vaccine 1996. Wattigney et al, Pediatrics 2001. IOM 1994. \nWork group interpretation\nFor adults at increased risk of poliovirus exposure who were previously \nvaccinated, how substantial are the desirable anticipated effects of \nreceiving a booster dose of IPV?EtRDomain: Benefits & Harms\nMinimal Small Moderate Large VariesDon’t \nknow\nWork group interpretation\nFor adults at increased risk of poliovirus exposure who were previously \nvaccinated, how substantial are the undesirable anticipated effects of \nreceiving a booster dose of IPV?EtRDomain: Benefits & Harms\nMinimal Small Moderate Large VariesDon’t \nknow\nWork group interpretation\nFor adults at increased risk of poliovirus exposure who were previously \nvaccinated, do the desirable effects of receiving a booster dose of IPV \noutweigh the undesirable effects?EtRDomain: Benefits & Harms\nAnticipated \nbenefits \noutweigh \nanticipated \nharmsAnticipated \nharms outweigh \nanticipated \nbenefitsVaries Don’t know\nPublic Knowledge and Beliefs about Poliovirus\nAnnenberg Science Knowledge (ASK) Survey*, October 2022\n*Nationally representative panel of 1,572 US adults surveyed by SSRS for the Annenberg Public Policy Center of the University ofPennsylvania from October 11 -18, 2022; this \nwas 9thwave of the ASK survey whose respondents were first empaneled in April 2021.\nWhat U.S. Adults Know and Believe About Polio and the Bivalent Covid Booster | The Annenberg Public Policy Center of the Univ ersity of Pennsylvania\n▪85% said they were likely \nto recommend that an \neligible person in their \nhousehold get \nvaccinated with the polio \nvaccine \nWork group interpretation\nDoes the target population (adults at increased risk of poliovirus \nexposure who were previously vaccinated) feel that the desirable effects \nof a booster dose are large relative to undesirable effects?EtRDomain: Values of Target Population\nNoProbably \nnoProbably \nyesYes VariesDon’t \nknow\nWork group interpretation\nIs there important uncertainty or variability in how much people value \nthe main outcome (prevention of paralytic poliomyelitis)?EtRDomain: Values of Target Population\nImportant \nuncertainty \nor variabilityProbably \nimportant \nuncertainty \nor variabilityProbably not \nimportant \nuncertainty \nor variabilityNo \nimportant \nuncertainty \nor variabilityNo known \nundesirable \noutcomes\n▪Current recommendation (“Adults who have had a primary series of OPV or IPV and \nwho are at increased risk [of exposure to poliovirus] can receive another dose of \nIPV.”) is long -standing and is generally accepted and feasible\n▪If “at increased risk of exposure” group is expanded (e.g., to include previously \nvaccinated adults in certain US areas with poliovirus circulation), feasibility might be \naffected\n▪New York State and New York City experience in 2022\n–No significant IPV supply issuesConsiderations for Acceptability, Feasibility, and Resources\nWork group interpretation\nIs the intervention (providing a booster IPV dose to adults at increased \nrisk of poliovirus exposure who previously completed a primary polio \nvaccination series) acceptable to key stakeholders?EtR Domain: Acceptability to Key Stakeholders\nNoProbably \nnoProbably \nyesYes VariesDon’t \nknow\nWork group interpretation\nIs the intervention (providing a booster IPV dose to adults at increased \nrisk of poliovirus exposure who previously completed a primary polio \nvaccination series) a reasonable and efficient allocation of resources?EtR Domain: Resource Use\nNoProbably \nnoProbably \nyesYes VariesDon’t \nknow\nWork group interpretation\nIs the intervention (providing a booster IPV dose to adults at increased \nrisk of poliovirus exposure who previously completed a primary polio \nvaccination series) feasible to implement?EtRDomain: Feasibility\nNoProbably \nnoProbably \nyesYes VariesDon’t \nknow\n▪No known differences in response to primary series by socioeconomic group in US \nsetting\n▪No groups or settings known to be disadvantaged by current recommendation\n▪Potential increased equity by boosting immunity in those at increased risk of \nexposure, especially persons with potential occupational exposures to poliovirusEquity Considerations from Work Group\nWork group interpretation\nWhat would be the impact (of providing a booster IPV dose to adults at \nincreased risk of poliovirus exposure who previously completed a \nprimary polio vaccination series) on health equity?EtRDomain: Equity\nReduced \nequityProbably \nreduced\nequityProbably \nno impactProbably \nincreased \nequityIncreased \nequityVariesDon’t \nknow\nIPV booster for adults at increased risk of poliovirus exposure who have \npreviously completed a primary polio vaccination seriesWork Group Judgement: Balance of Consequences\nUndesirable\nconsequences \nclearly\noutweigh \ndesirable \nconsequences \nin most settingsUndesirable\nconsequences \nprobably \noutweigh\ndesirable \nconsequences \nin most settingsThe balance \nbetween \ndesirable and \nundesirable \nconsequences \nis closely \nbalanced or \nuncertainDesirable\nconsequences \nprobably\noutweigh \nundesirable \nconsequences \nin most settingsDesirable\nconsequences \nclearly\noutweigh \nundesirable \nconsequences \nin most settingsThere is \ninsufficient \nevidence to \ndetermine the \nbalance of \nconsequences\n▪Risk-based\n▪Shared clinical decision -making\nProposed Language:\n▪Adults who have received a primary series of tOPV or IPV in any combination and \nwho are at increased risk of poliovirus exposure may receive another dose of IPV. \nAvailable data do not indicate the need for more than a single lifetime booster \ndose with IPV for adults.Majority of Work Group Agree with Current \nRecommendation for Adult IPV Booster\nSituations that put adults at increased risk of exposure to poliovirus include:\n▪Travelers who are going to countries where polio is epidemic or endemic (For additional information, \nsee Polio: For Travelers).\n▪Laboratory and healthcare workers who handle specimens that might contain polioviruses.\n▪Healthcare workers or other caregivers who have close contact with a person who could be infected \nwith poliovirus.Clinical Considerations\n▪ACIP voting members\n–Oliver Brooks (Chair)\n–Lynn Bahta\n–Sybil Cineas\n▪Liaisons\n–Lynn Fisher, American Academy of Family Physicians\n–Chandy C John, American Academy of Pediatrics \n–Sandra Fryhofer , American Medical Association\n–Kathy Kudish, Association of Immunization Managers\n–Marcus Plescia , Association of State and Territorial Health Officials\n–Paul R Cieslak , Council of State and Territorial Epidemiologists\n–Christine Hahn, Council of State and Territorial Epidemiologists\n–Tina Q. Tan, Infectious Diseases Society of America\n–Adenike Shoyinka , Infectious Diseases Society of America\n–Mary Wilson, International Society of Travel Medicine\n–Jaqueline Lawler, National Association of County and City Health Officials\n–Kathy Edwards, Pediatric Infectious Diseases Society\n–Joseline Zafack , Public Health Agency of Canada*\n–Oliver Baclic , Public Health Agency of Canada*Polio Work Group Members\n*In the event of a Work Group poll, CDC, FDA, and Public Health Agency of Canada members are not included.▪Consultants\n–Edwin Asturias\n–Doug E Campos -Outcalt *\n–Emily Lutterloh\n–Walt Orenstein\n–Jennifer Rosen\n–Eli Rosenberg\n▪Ex Officio\n–Robin Levis , FDA*\n–Robin Wisch , FDA*\n▪CDC*\n–Achal Bhatt\n–Stephanie Bialek\n–Thomas Clark\n–Brian Edlin\n–Concepcion Estivariz\n–Halle Getachew\n–Sarah Kidd\n–Janelle King\n–M. Steve Oberste\n–Janell Routh\n–Eileen Yee\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position o f the Centers for Disease Control and Prevention.\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation use. No rights are implied or extended for use in printing or \nany use by other CDC CIOs or any external audiences.Questions and Discussion", "summary": "Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/02-POLIO-Kidd-Jun-2023.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 75}
{"title": "01 influenza talbot 508", "content": "Seasonal Influenza Vaccines\nH. Keipp Talbot, MD, MPH\nChair, Influenza Work Group \nAdvisory Committee on Immunization Practices\nJune 21, 2023\nInfluenza Work Group\nACIP Members\nKeipp Talbot (Chair)\nCamille Kotton\nJamie Loehr\nEx Officio\nTimothy Brennan (FDA)\nUzo Chukwuma (IHS)\nMichael Cooper (NIH)\nJeffrey Kelman (CMS)\nValerie Marshall (OASH)\nCynthia Nolletti (FDA)\nChris Roberts (NIH)Liaison Representatives \nand Consultants\nRobert Atmar\nKevin Ault\nEd Belongia\nHank Bernstein\nThomas Boyce\nKris Bryant\nSarah Coles\nJeff Duchin\nAlicia Fry\nSandra Fryhofer\nDenise Jamieson\nWendy Keitel\nMarie -Michèle Léger\nSusan LettKrissy Moehling\nZackary Moore\nKathy Neuzil\nJesse Papenburg\nWilliam Schaffner\nRob Schechter \nKen Schmader \nTamara Sheffield\nAngela Sinilaite\nPatsy Stinchfield \nPeter Szilagyi\nMatthew Zahn\nCDC Lead\nLisa Grohskopf\n2\nRecent Work Group Activity\n▪\n▪\n–\n–Preparation of proposed 2023 -24 influenza statement.\nDiscussion of safety of influenza vaccination of persons with egg allergy.\nEvidence review, GRADE, and Evidence to Recommendations framework.\nDevelopment of proposed recommendations concerning vaccination of \npersons with a history of severe allergic reaction to egg.\n3\nSession Overview\n▪Influenza Vaccination of Persons with Egg Allergy: Background, Work Group \nConsiderations, and Evidence to Recommendations Discussion.\n▪Proposed recommendations for the 2023 -24 influenza season.\n4\n5\nFor more information, contact CDC\n1-800-CDC-INFO (232- 4636)\nTTY:  1- 888- 232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation use. No rights are implied or extended for use in printing or \nany use by other CDC CIOs or any external audiences.", "summary": "Seasonal Influenza Vaccines H. Keipp Talbot, MD, MPH Chair, Influenza Work Group  Advisory Committee on Immunization Practices June 21, 2023 Influenza Work Group ACIP Members Keipp Talbot (Chair) Camille Kotton Jamie Loehr Ex Officio Timothy Brennan (FDA) Uzo Chukwuma (IHS) Michael Cooper (NIH) Jeffrey Kelman (CMS) Valerie Marshall (OASH) Cynthia Nolletti (FDA) Chris Roberts (NIH)Liaison Representatives  and Consultants Robert Atmar Kevin Ault Ed Belongia Hank Bernstein Thomas Boyce Kris…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/01-influenza-talbot-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 5}
{"title": "02 influenza grohskopf 508", "content": "National Center for Immunization & Respiratory Diseases\nInfluenza Vaccination of Persons with Egg Allergy:\nEvidence to Recommendations Discussion and Work Group Considerations\nLenee H. Blanton\nLisa A. Grohskopf\nInfluenza Division, CDC/NCIRD\nAdvisory Committee on Immunization Practices\nJune 21, 2023\n•Donna Hummell\n•Karen Broder\n•Pedro Moro\n•Geta Aynalem\n•Shashi Sharma\n•Elaine Miller\n•Andrew Leidner\n•Rebecca Morgan\n•Doug Campos -OutcaltAcknowledgements\n2\nBackground\n•Affects approximately 1 -3% of children by age 3 years.1,2\n•Resolves for many during later childhood and adolescence .\n–In one study,3\n›4% developed tolerance by age 4 years, \n›12% by age 6 years, \n›37% by age 10 years, \n›68% by age 16 years.\n•Reactions range from mild to life -threatening.\n•Diagnosis:\n–Clear history of immediate allergic reaction to egg or egg -containing foods.2\n–Skin prick testing (SPT) or estimation of egg -specific IgE levels.2Egg Allergy\n1. Eggesbo M et al. Allergy 2001;56(5):403 -411\n2. Erlewyn -Lajeunesse M et al. BMJ 2009;339:b3680.3. Savage JH et al. J Allergy Clin Immunol 2007;120(6):1413 -7.\n4\nOvalbumin Content of U.S. Influenza Vaccines, 2022 -23 \nVaccine (manufacturer) Approved age \nindicationOvalbumin, mcg/dose* \n(per package insert)\nEgg-based\nAfluria Quadrivalent (Seqirus) ≥6 mos <1\nFluarix Quadrivalent (GSK) ≥6 mos ≤0.05\nFluLaval Quadrivalent (GSK) ≥6 mos ≤0.3\nFluzone Quadrivalent (Sanofi Pasteur) ≥6 mos Not stated\nFluMist Quadrivalent (AstraZeneca) 2 through 49 yrs <0.024\nFluad Quadrivalent (Seqirus) ≥65 yrs ≤1\nFluzone High -Dose Quadrivalent (Sanofi Pasteur) ≥65 yrs Not stated\nEgg-free\nFlucelvax Quadrivalent (Seqirus) ≥6 mos Egg-free\nFlublok Quadrivalent (Sanofi Pasteur) ≥18 yrs Egg-free\n* 0.5 mL for injectable vaccines and 0.2 mL for LAIV 5\n•Persons with a history of egg allergy of any severity should receive influenza vaccine.\n•Any licensed, recommended influenza vaccine (i.e., any IIV4, RIV4, or LAIV4) that is \notherwise appropriate can be used.\n•For persons with previous reactions to egg involving symptoms other than urticaria:\n–“If a vaccine other than ccIIV4 or RIV4 is used, the selected vaccine should be \nadministered in an inpatient or outpatient medical setting, including but not \nnecessarily limited to hospitals, clinics, health departments, and physician \noffices. Vaccine administration should be supervised by a health care provider \nwho is able to recognize and manage severe allergic reactions.”\n•No specific observation period recommended.Current ACIP Recommendations1\n1. CDC/ACIP . MMWR Recomm Rep 2022;71(No. RR -1):1–28. IIV4= quadrivalent inactivated influenza vaccine\nLAIV4=quadrivalent live attenuated influenza vaccine\nccIIV4=quadrivalent cell culture based inactivated influenza vaccine\nRIV4= quadrivalent recombinant influenza vaccine6\n•American Academy of Pediatrics\n–Since 2016 -17, no additional measures recommended for persons with egg allergy.1\n–“Children with egg allergy can receive any influenza vaccine without any additional precautions\nbeyond those recommended for all vaccines.”2\n–Measures related to use of specific vaccines, observation periods, or restricting vaccination to \nspecific medical settings not warranted and constitute a barrier to vaccination.3\n–Not necessary to inquire about or screen for egg allergy prior to influenza vaccination.3\n•Joint Task Force, AAAAI/ACAAI\n–“No special precautions beyond those recommended for the administration of any vaccine to \nany patient are necessary for administration of influenza vaccine to egg allergic individuals.”4Influenza Vaccines and Egg Allergy: Other Guidance\n1. Recommendations for Prevention and Control of Influenza in Children, 2016 –2017 | Pediatrics | American Academy of Pediatrics (aa p.org)\n2. Recommendations for Prevention and Control of Influenza in Children, 2022 –2023 | Pediatrics | American Academy of Pediatrics (aa p.org) .\n3. AAP . Technical Report for the 2022 -23 Recommendations for the Prevention and Control of Influenza in Children, 2022 -23\n4. Greenhawt M et al . Ann Allergy Asthma Immunol 2018;120:49 -52. 7\n•From chapter titled “Preventing and Managing Adverse Reactions”:\n–“Although allergic reactions are a common concern for vaccine providers, these \nreactions are uncommon and anaphylaxis following vaccines is rare, occurring at \na rate of approximately one per million doses for many vaccines. Epinephrine \nand equipment for managing an airway should be available for immediate use.”General Best Practices Guidelines for Immunization1\n1. Kroger AT et al. https://www.cdc.gov/vaccines/hcp/acip -recs/general -recs/index.html\n8\n•Vaccine skin testing prior to vaccination.1,2\n–Skin prick and/or intradermal testing with dilution of vaccine\n–If positive, vaccination deferred or administered via alternative dosing protocol\n•Graded administration of vaccine.3\n–Incrementally increasing volumes, often in 5 to 6 steps; sometimes with dilutions in early steps\n–E.g., 0.05 mL of 1:100 dilution →0.05 mL of 1:10 dilution →0.05 mL→0.1 mL→0.15 mL→0.2 mL, \nwith observation periods after each dose (e.g., 15 minutes).\n•Split dosing of vaccine.4\n–Most commonly 10% of dose volume →observation period →remaining 90% of dose volume, \noften with additional observation after final dose.Past Approaches to Influenza Vaccination of Persons with \nEgg Allergy (Not Currently Recommended)\n1. Bierman CW et al. J Infect Dis 1977;136:S652 -S655.\n2. Miller JR et al. J Allergy Clin Immunol 1983;71:568 -173.3. Murphy KR et al. J Pediatr 1985;106(6):931 -933.\n4. James JM et al. J Pediatr 1998;133:624 -628.\n9\n•Whether t o no longer recommend additional safety measures for \npersons with egg allergy of any severity, beyond what is recommended \nforany other persons presenting for influenza vaccination.\n–In the discussion that follows, the proposed intervention is to no longer make \nthe recommendation regarding vaccination setting for those with a history of \nsevere allergic reaction to egg.Policy Question\n1\n0\nEtR Domain 1: Public Health Importance\n•Egg allergy more common in younger children, and often co -exists with asthma:\n–In a cross -sectional survey of 38,408 children,1\n›Egg allergy prevalence was 0.9% overall; 1.3% for those  <5 yrs.\n›Asthma prevalence higher with egg allergy (46.5%) with other 8 most common food allergies (33.2%).\n•Younger children and people with asthma are at increased risk of severe influenza \nillness.Is Vaccination of Egg -Allergic Persons an Issue of Public \nHealth Importance?\n1.Samady W, Warren C, Wang J, et al.  Egg allergy in US children. J Allergy Clin Immunol Pract. 2020;8(9):3066 -73. 12\nPublic Health Importance: WG Considerations\n•Current recommendations might be \na real or perceived barrier to \nvaccination (e.g., by promoting \nhesitancy based on safety concerns, \nor providing a reason to decline \nvaccination).\n-No data specifically examining or \nconfirming that current \nrecommendations are a barrier found, \nbut existence of real or perceived \nbarriers is plausible.\n13•Current recommendations might be \nless of a barrier now, since cell -\nbased (egg -free) inactivated vaccine \nis approved for ages ≥6 mos. \n-However, there is only one such vaccine \nlicensed for children <18 years, compared \nwith four egg -based vaccines available for \nthis age group. \nIs Vaccination of Egg -Allergic Persons an Issue of Public \nHealth Importance?\n14\n0\n6\n33\n61\n0\n0No\nProbably no\nProbably yes\nYes\nVaries\nDon't know% of respondents (N=18)\nEtR Domain 2: Benefits and Harms\n•Does the available evidence concerning the safety of influenza vaccines \nin persons with a history of egg allergy favor routine vaccination without \nadditional safety measures, regardless of severity of previous allergic \nreaction to egg?\n–Review focused on Harms (safety) —did not include review of \neffectiveness/efficacy data.Review Question\n16\nPopulation, Intervention, and Comparators\n▪Population: Persons of any age with a history of allergy to eggs, or who \nhave had an allergic reaction to influenza vaccine believed to be \nsecondary to egg allergy.\n▪Intervention: Any influenza vaccine.\n▪Comparators: Placebo, non egg -based influenza vaccine, non -influenza \ncontrol vaccine, no vaccine, no comparator\n17\nOutcomes\nImportant\n•Allergic reaction symptoms \nrequiring outpatient or emergency \ndepartment medical attention†\n•Allergic reaction including \ncardiovascular symptoms, \nrespiratory symptoms, angioedema, \nor generalized urticariaCritical\n•Death\n•Anaphylaxis meeting Brighton \ncriteria Levels 1 -3*\n•Anaphylaxis otherwise \nclassified*\n•Allergic symptoms requiring \nhospitalization\n* These two outcomes are combined in the tables that follow.\n† Includes instances treated with medications, without explicit mention of outpatient or emergency department care .18Within 4 hours of vaccination:\nStudy Designs, Vaccines, and Comparison Groups\n▪47 reports describing 52 studies.\n•1 randomized study (compared full -dose with 10%/90% split dose).\n•1 VAERS report summary.\n•Remainder retrospective/prospective cohort studies and case series.\n•2 involved only recombinant vaccine (egg -free).\n▪No studies include a relevant comparison group (e.g., an alternative or no vaccine).\n▪14 abstracts only (no related paper found).\n▪All studies were reviewed descriptively.\n▪28 reports (31 studies) included in GRADE:\n•Egg-based vaccines only (seasonal and monovalent).\n•Full-dose or split -dose administration.\n•For the randomized study, full -and split -dose groups combined; treated as a cohort study.\n•Data with unknown/unclear vaccine type, unspecified administration protocol, graded (≥3 steps) \ndosing, and/or unknown denominator excluded.\n•Since there are no comparators, data are summarized as frequencies. 19\nSummary of Events by Vaccine Type: Egg Allergy of All severities\nOutcome Seasonal IIVs* Monovalent IIVs* LAIV Importance Certainty\nDeath 0/1591 (0%) 0/5235 (0%) 0/1129 (0%) Critical Very low\nAnaphylaxis 0/1591 (0%) 0/5235 (0%) 0/1129 (0%) Critical Very low\nReaction requiring hospitalization 0/1591 (0%) 0/5235 (0%) 0/1129 (0%) Critical Very low\nReaction requiring outpatient/ED \nattention (includes those given \nsymptomatic medications)3/1591 (0.2%) 77/5235 (1.5%) 0/1129 (0%) Important Very low\nAllergic reaction including \ncardiovascular symptoms, respiratory \nsymptoms, angioedema, or \ngeneralized urticaria5/1591 (0.3%) † 33/5235 (0.6%) 10/1129 (0.8%) Important Very low\n20*Includes several papers for which vaccine type not explicitly stated, but presumed based upon season, study \nlocation, and/or use of graded/split dosing.  Seasonal IIV data include one paper describing a virosomal vaccine.\n†One study reported 6 instances of reactions including “wheezing, eczema exacerbation, or hives on chest”, but \nnot specifying number with each symptom.  If assumed that all six included wheezing, frequency would be \n11/1591=0.7% \nSummary of Events by Vaccine Type: Persons with Anaphylaxis to Egg\nOutcome Seasonal IIVs* Monovalent IIVs* LAIV Importance Certainty\nDeath 0/322 (0%) 0/68 (0%) 0/412 (0%) Critical Very low\nAnaphylaxis 0/322 (0%) 0/68 (0%) 0/412 (0%) Critical Very low\nReaction requiring hospitalization 0/322 (0%) 0/68 (0%) 0/412 (0%) Critical Very low\nReaction requiring outpatient/ED attention 0/295 (0%) 0/68 (0%) 0/412 (0%) Important Very low\nAllergic reaction including cardiovascular \nsymptoms, respiratory symptoms, \nangioedema, or generalized urticaria0/291 (0%) 0/68 (0%) 0/27 (0%) Important Very low\n21*Includes several papers for which vaccine type not explicitly stated, but presumed to be IIV based upon season, \nstudy location, and/or use of graded/split dosing.\nSummary of Evidence for Outcomes of Interest\nOutcome Importance Included in \nprofileCertainty\nDeath Critical Yes Very low\nAnaphylaxis Critical Yes Very low\nAllergic reaction symptoms requiring hospitalization Critical Yes Very low\nAllergic reaction symptoms requiring outpatient or \nemergency department medical attentionImportant Yes Very low\nAllergic reaction including cardiovascular symptoms, \nrespiratory symptoms, angioedema, or generalized urticariaImportant Yes Very low\n22\nReport of Brighton Level 1 Anaphylaxis\n▪One report of Brighton Level 1 anaphylaxis in person with “possible” egg allergy \nwithin 30 minutes of receiving monovalent vaccine.\n•In paper summarizing VAERS reports following monovalent pandemic influenza vaccine during \n2009 -10 season.1\n•Unclear from paper whether documented to be egg -allergic.\n▪Doses administered that season unknown\n•Reaction not included in counts in GRADE evidence profiles (as denominator undefined).\n▪Paper states approximately 127 million doses distributed that season.\n▪Other reactions: \n•2 of respiratory hypersensitivity\n•1 sensation of throat closure\n1. Halsey NA, et al. Vaccine. 2013 Dec 9;31(51):6107 -12. doi: 10.1016/j.vaccine.2013.09.066. Epub 2013 Oct 8. PMID: 24120547 .\nDescriptions Of Reactions Following Egg -free Vaccines\n24•Woo et al  2015, 2017: summaries of VAERS reports following \nrecombinant influenza vaccine (RIV):\n•Reports of serious allergic reactions following RIV, some of which occurred \namong persons with egg allergy.\n•RIV is egg, gelatin, antibiotic, and preservative -free.\n•Authors note that the occurrence of such reactions might reflect an \nunderlying predisposition to atopy.\n•Reports also highlight unpredictability of severe allergic reactions, and \nimportance of being prepared in all vaccination settings, for all \nrecipients, and with all vaccines. \nLimitations and WG Considerations\n▪Observational data with no comparator groups meeting criteria.\n▪Some data only available from abstracts.\n▪Many (particularly older) studies employed skin testing with egg proteins and/or \nvaccine prior to decision to vaccinate.\n▪Considerable variability in level of detail in which outcomes are described.\n▪Observation time post -vaccination varied; time elapsed post -vaccination not often \nreported for delayed reactions.\n•Observation for immediate reactions under 4 hours for most studies; generally 30 min to 2 hours.\n▪Ovalbumin content was not reported/unknown in most instances. \n•In most instances where noted, was <1µg/dose; in some cases substantially less. \n•Difficult to know how this compares with current vaccines, since expressed as an upper limit.\n▪Data specifically for persons with anaphylaxis to egg were limited.\n•Not all studies specified that persons with severe egg allergy were included.\n•Where included, not all studies reported reactions specifically for this subgroup. 25\nEgg Allergy and Anaphylaxis Reports after IIVs in \nVAERS, 2017 -2022\n•178 anaphylaxis reports after any IIV\n•18 had an egg allergy (based on VAERS report)\n•Clinical review revealed 7 reports of anaphylaxis and egg allergy (all in 2017 -18):\n•4 in children (ages 2, 4, 9, 11 yrs);  3 in adults (ages 21, 52, 61 yrs)\n•4 Brighton level 1; 1 Brighton level 3; 2 did not meet Brighton\n•Influenza vaccines:\n›Fluarix quadrivalent: 2\n›Fluzone quadrivalent: 2\n›Fluvirin trivalent: 1\n›Flucelvax quadrivalent: 1\n›Flublok quadrivalent: 1\n•Difficult to assess if reaction was due to egg protein due to limited laboratory data.\n26 Vaccine Adverse Event Reporting System (VAERS) (hhs.gov)\nHow Substantial are the Undesirable Anticipated Effects? \n27\n39\n44\n6\n0\n11\n0Minimal\nSmall\nModerate\nLarge\nVaries\nDon't Know% ofrespondents (N=18)\nEtR Domain 3: Values\n•No direct evidence found.\n•Change in recommendations might be reassuring to some who have \nwanted to be vaccinated but were hesitant/perceived it is unsafe;\n•Or might be source of concern.\n–WG member expressed that change might be viewed unfavorably if it is \nperceived as trade -off between safety vs. increasing coverage/reducing missed \nopportunities for vaccination.Does the Target Population Feel that the Desirable Effects \nare Large Relative To Undesirable Effects?\n29\nDoes the Target Population Feel that the Desirable Effects \nare Large Relative To Undesirable Effects?\n30\n0\n6\n22\n17\n6\n50No\nProbably no\nProbably yes\nYes\nVaries\nDon't Know% of respondents (N=18)\n•No direct evidence found.\n–Presumably, greater value attached to the more serious outcomes (death, \nanaphylaxis, hospitalization).Is There Important Uncertainty About, or Variability In, How \nMuch People Value the Main Outcomes?\n31\nIs there important uncertainty about, or variability in, how \nmuch people value the main outcomes?\n32\n0\n28\n67\n6\n0Important uncertainty or variability\nProbably important uncertainty or \nvariability\nProbably not important uncertainty or \nvariability\nNo important uncertainty or variability\nNo known undesirable outcomes% of respondents (N=18)\nEtR Domain 4: Acceptability\n•No direct evidence found.\n•Several US professional societies (AAP , AAAAI, ACAAI) already recommend no special \nmeasures (screening, observation periods, selection of specific vaccines, specific \nvaccination settings) for those with egg allergy.\n•As of 2022 -23, package inserts for egg -based vaccines continue to carry a \ncontraindication of severe hypersensitivity reaction to any vaccine components.\n–However, ACIP has previously recommended influenza vaccination with any appropriate vaccine \n(egg -based or not), regardless of severity of reaction to egg.Is the Intervention Acceptable to Key Stakeholders?\n34\nAcceptability: WG Considerations\n•Alignment of recommendations \namong public health organizations \nand professional societies facilitates \nconsistent messaging to providers \nand patients.\n35•Concern that some settings might \nnot be prepared to manage severe \nreactions (e.g., retail).\n•Acceptability will be severely \nimpacted if anaphylaxis occurs in a \nsetting unprepared to manage it. \n-Importance of stressing that every\nsetting must be able to manage \nanaphylaxis, or should not administer \nany vaccines to any recipient. \n•Concer n for potential liability issues.\nIs the Intervention Acceptable to Key Stakeholders?\n36\n0\n0\n56\n44\n0\n0No\nProbably no\nProbably yes\nYes\nVaries\nDon't know% of respondents (N=18)\nEtR Domain 5: Resource Use\n•No economic analysis was conducted.\n–The target population is small.\n–Lack of data for some factors.\n›No reliable estimate of the proportion of those with egg allergy who have had \nsevere reaction to egg.\n›Proportions of individuals with egg allergy by age uncertain.\n›Proportions of persons receiving egg -based vs. egg -free vaccines uncertain.\n•Primary emphasis of assessment was safety rather than cost.Is the Intervention a Reasonable and Efficient Allocation of \nResources?\n38\n•CMS payment allowances and VFC costs higher for egg -free vaccines that are approved for children \n(rounded to nearest dollar):Relative Costs of Egg -Based vs. Egg -Free Influenza Vaccines\n39Vaccine (based on 0.5mL dose) CMS Rate 2022 -231 VFC List 2023 -242\nEgg-based\nAverage for egg -based vaccines for ≥6 mos:    Multidose $20.00 $20.00\nAverage for egg -based vaccines for ≥6 mos:    Preservative -free $22.00 (IIV4s)\n$27.00 (LAIV4)$21.00 (IIV4s)\n$24.00 (LAIV4)\nFluzone High -Dose Quadrivalent: Preservative -free (≥65 yrs only) $70.00 -\nFluad Quadrivalent:                        Preservative -free (≥65 yrs only) $72.00 -\nEgg-free\nFlucelvax Quadrivalent:   Multidose (≥6 mos) $31.00 $29.00\nPreservative -free (≥6 mos) $32.00 $30.00\nFlublok Quadrivalent        Preservative -free (≥18 yrs only) $70.00 -\n1.https://www.cms.gov/Medicare/Medicare -Fee-for-Service -Part-B-Drugs/McrPartBDrugAvgSalesPrice/VaccinesPricing\n2.CDC Vaccine Price List (Private sector cost per dose)\nResource Use: WG Considerations\n•Removing existing restrictions \ncould result more efficient \nallocation of resources, if data \nsuggest no or minimal increase in \nadverse events.\n40•Change in recommendations and \nlower cost of egg -based vaccines \nmight lead to their increased use, \nwhich might be associated with \nincreased costs if these is an \nincrease in reactions requiring \nmedical attention.\nIs the Intervention a Reasonable and Efficient Allocation of \nResources?\n41\n0\n0\n24\n76\n0\n0No\nProbably no\nProbably yes\nYes\nVaries\nDon't know% of respondents (N=17)*\n* Answer from one respondent who selected “Probably yes” and “Yes” excluded\nEtR Domain 6: Equity\n•No direct evidence found.\n•Some racial/ethnic groups at increased risk for severe influenza illness, highlighting \nimportance of vaccination:\n–Influenza associated hospitalization and ICU admission rates higher among Black, Hispanic, and \nAmerican Indian/Alaska Native children <4 yrs of age compared with White children.1\n–Black children were disproportionately represented among children with egg allergy in one \nseries (23.4%, relative to comprising 13.2% of the U.S. pediatric population).2\n–If current recommendations are a barrier to vaccination, the intervention could improve equity \nwith regard to risk of severe influenza illness.What Would Be the Impact on Health Equity?\n431.O’Halloran et al J AMA Netw Open. 2021 Aug 2;4(8):e2121880\n2.Samady W et al. J Allergy Clin Immunol Pract. 2020 Oct;8(9):3066 -3073.e6. doi: 10.1016/j.jaip.2020.04.058 . \n•Issues related to trust in the healthcare system, from the patient’s \nperspective :\n–A change in recommendations might mean vaccination occurs more widely in \nmore settings than previously, and perhaps increased use of egg -based vaccines \nrather than egg -free vaccines in some settings. \n–The fact that egg -based vaccines are less expensive might reinforce belief that \nproviders/ healthcare systems do not care to use the necessary resources to \nprovide a potentially safer vaccine.Equity: WG Considerations\n44\nWhat Would Be the Impact on Health Equity?\n45\n0\n17\n11\n50\n0\n6\n17Reduced\nProbably reduced\nProbably no impact\nProbably increased\nIncreased\nVaries\nDon't know% of respondents (N=18)\nEtR Domain 7: Feasibility\nIs the Intervention Feasible to Implement?\n•Considerations favoring feasibility:\n-The proposed change i s a simplification \nof the previous recommendation.\n-It does not specify particular vaccines.\n-It does not change recommendations \nfor emergency equipment and \nresources.\n›The General Best Practices indicate that  \nepinephrine and equipment to manage \nan airway should be available in all \nvaccination settings.1\n47•Consideration against feasibility:\n-Vaccination settings not already \nprepared to manage severe allergic \nreactions would need to address \nthese needs. \n›However, all settings are already \nrecommended to be prepared for \nsevere allergic reactions when \nadministering any vaccine to any \nrecipient.1\n1. Kroger AT et al. https://www.cdc.gov/vaccines/hcp/acip -recs/general -recs/index.html.    \nIs the Intervention Feasible to Implement?\n48\n0\n0\n11\n89\n0\n0No\nProbably no\nProbably yes\nYes\nVaries\nDon't know% of respondents (N=18)\nBalance of Consequences and Sufficiency \nof Information\nBalance of Consequences\n50\n0\n0\n0\n39\n61\n0Undesirable consequences clearly outweigh desirable consequences\nin most settings\nUndesirable consequences probably outweigh desirable consequences\nin most settings\nThe balance between desirable and undesirable consequences is\nclosely balanced or uncertain\nDesirable consequences probably outweigh undesirable consequences\nin most settings\nDesirable consequences clearly outweigh undesirable consequences\nin most settings\nThere is insufficient evidence to determine the balance of consequences0 10 20 30 40 50 60 70 80 90 100% of respondents (N=18)\nIs There Sufficient Information to Move Forward With a \nRecommendation?\n51•Of 18 respondents,\n–18 responded “Yes”\n–0 responded “No”\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the \nofficial position of the Centers for Disease Control and Prevention.\n\nSearch\n•First search 03 -14-2019; updated search 10 -26-2022.\n•Medline, Embase, PsycInfo, CINAHL, NTIS, Scopus, Cochrane Library, \nClinicalTrials.gov; no date or language restriction.\nIncluded reports\n•Randomized Controlled trials, Observational studies, Case reports, Case series, \nSafety surveillance system reports (including Vaccine Adverse Event Reporting \nSystem and other safety surveillance system reports).\n•Abstracts for which no papers found were included.\nExcluded reports\n•Animal studies, duplicate reports, reviews*, clinical trial registry summaries.*Literature Search, Inclusion/Exclusion Criteria\n* Used to help identify other potentially relevant reports 53\nPRISMA Diagram\n381 reports excluded\n•255 review/other non -primary source\n•67 wrong study design\n•20 wrong patient population\n•16 abstract (paper found) or registry summary\n•6 wrong intervention\n•3 wrong outcomes\n•14 insufficient information477 reports retrieved\n47 reports abstracted428 full -text reports assessed454 reports screened23 duplicates removed\n26 studies irrelevant\n19 reports excluded from GRADE\n•12 unclear dosing protocol\n• 4 unclear vaccine\n• 2 egg -free vaccine\n• 1 graded dosing only28reports included in GRADE\n54\n1. Question and PICO\nPolicy \nquestion:Whether available evidence concerning safety of influenza vaccines in persons with a history of \negg allergy favors routine vaccination without additional safety measures, regardless of severity of \nprevious allergic reaction to egg.  \nPopulation Persons of any age with a history of allergy to eggs, or who have had an allergic reaction to \ninfluenza vaccine believed to be secondary to egg allergy.\nIntervention Receipt of any influenza vaccine.  \nComparison Placebo, nonegg -based influenza vaccine, non -influenza control vaccine, no vaccine, no \ncomparator.\nOutcomes Critical:\n•Death\n•Anaphylaxis meeting Brighton criteria Levels 1 -3*\n•Anaphylaxis otherwise classified*\n•Allergic reaction symptoms requiring hospitalization\nImportant:\n•Allergic reaction symptoms requiring outpatient or emergency department medical attention†\n•Allergic reaction including cardiovascular symptoms, respiratory symptoms, angioedema, or \ngeneralized urticaria\n*These  outcomes are combined in the evidence profile tables. \n†Includes instances treated with medications, without explicit mention of outpatient or emergency department care. 55\n2. Outcomes and Rankings\nOutcome Importance Included in \nevidence profile\nDeath Critical Yes\nAnaphylaxis meeting Brighton criteria Levels 1 -3* Critical Yes\nAnaphylaxis otherwise classified* Critical Yes\nAllergic reaction symptoms requiring hospitalization Critical Yes\nAllergic reaction symptoms requiring outpatient or \nemergency department medical attention†Important Yes\nAllergic reaction including cardiovascular symptoms, \nrespiratory symptoms, angioedema, or generalized urticariaImportant Yes\n56*These outcomes are combined in the evidence profile tables. \n†Includes instances treated with medications, without explicit mention of outpatient or emergency department care.\n3a. Summary of Studies and Outcomes —Seasonal IIV (1)\n*Adapted from Murad MH et al, BMJ Evid Based Med 2018;23(2):60 -62.  Domains assessed included Selection, Ascertainment, \nCausality (excluding items pertaining to alternative causes and dose -response effect), and Reporting\n†Abstract only.Author \nPublication yearAge/other \ncharacteristicsN Comparator Events by outcome Methodological \nquality concern*\nAnvari 2011 Not specified 86 None None Unclear\nChung 2010 Skin test group: \nAverage 6.2\n(95%CI 5.1 -7.2) yrs\nNon -skin test \ngroup: Average 3.9 \n(95%CI 3.3 -4.5) yrs171 None None Moderate\nComeau 2016 † Not specified 88 None None Serious\nDes Roches 2012 -1 <2 yrs: 27\n2-4 yrs: 83\n5-11 yrs: 82\n>12 yrs: 37230 None None Low\nDesRoches 2012 -2 <2 yrs: 29\n2-4 yrs: 53\n5-11 yrs: 51\n>12 yrs: 4137 None None Low\nErlewyn -Lajeunesse 2010 † Not specified 16 doses None Cardiovascular, respiratory, angioedema, \nor generalized urticaria: 1 Moderate\n57\n3a. Summary of Studies and Outcomes —Seasonal IIV (2)\nAuthor \nPublication yearAge/other \ncharacteristicsN Comparator Events by outcome Methodological \nquality concern\nEsposito 2008 6.03 +/ -3.33 yrs 44 Non -allergic group Outpatient or emergency department \nmedical attention: 1\nCardiovascular, respiratory, angioedema, \nor generalized urticaria: 1 Low\nGreenhawt 2012 -1 Median 11 -12 mos 31 Comparison of full -vs. \nsplit -dose (combined in \nthis review)None Low\nGreenhawt 2012 -2 Median 12 mos at \ndiagnosis112 None None Low\nHotte 2008 † Not provided 115 None None Unclear\nHowe 2011 Not specified 69 Non -allergic group None Unclear\nJames 1998 Median 3 (1 -46) yrs 83 Non -allergic group Outpatient or emergency department \nmedical attention: 2\nCardiovascular, respiratory, angioedema, \nor generalized urticaria: 3Low\nLeo 2010 † Not provided 31 None None Unclear\nPark 2008 † Mean 36.1 +/ -19.1 \n(11 to 105 mos)45 None None Unclear\nPaschall 2011 † Mean 3.8 yrs 65 doses None None Unclear\nShimizu 2016 Median 15\n(IQR 13 -20) mos17 None None Low\nThanik 2010 Not specified 214 doses None None Unclear\n58*Adapted from Murad MH et al, BMJ Evid Based Med 2018;23(2):60 -62.  Domains assessed included Selection, Ascertainment, \nCausality (excluding items pertaining to alternative causes and dose -response effect), and Reporting\n†Abstract only.\n3b. Summary of Studies and Outcomes —Monovalent IIV (1)\nAuthor \nPublication yearAge/other \ncharacteristicsN Comparator Events by outcome Methodological \nquality concern*\nDidenko 2010 median 4 (2 -11) yrs 6 None None Moderate\nForsdahl 2012 Mean 6.25 yrs\n(10 mos -16.5 yrs)80 None Outpatient or emergency department \nmedical attention: 1\nCardiovascular, respiratory, angioedema, \nor generalized urticaria: 1 Moderate\nGagnon 2010 -1 173 <2 yrs\n280 2 -4 yrs\n277 5 -11 yrs\n100 ≥12 yrs830 Non -allergic group Outpatient or emergency department \nmedical attention: 4\nCardiovascular, respiratory, angioedema, \nor generalized urticaria: 6Low\nGagnon 2010 -2 Not specified 3460 None Outpatient or emergency department \nmedical attention: 68\nCardiovascular, respiratory, angioedema, \nor generalized urticaria: 26Unclear\nGreenhawt 2010 Mean 5.5 (range \n0.4-20.4) yrs105 Non -allergic group None Low\n59*Adapted from Murad MH et al, BMJ Evid Based Med 2018;23(2):60 -62.  Domains assessed included Selection, Ascertainment, \nCausality (excluding items pertaining to alternative causes and dose -response effect), and Reporting.\n3b. Summary of Studies and Outcomes —Monovalent IIV (2)\nAuthor \nPublication yearAge/other \ncharacteristicsN Comparator Events by outcome Methodological \nquality concern*\nLeo 2010 † Not specified 50 None None Unclear\nPaschall 2011 † Mean 3.8 yrs 66 None None Unclear\nPien 2010 Mean 3.7 +/ -3.0 yrs 59 None None Moderate\nPitt 2011 Mean 5.6 (1 -27) yrs 59 None None Moderate\nSchuler 2011 Mean 4.5 yrs \n(10 mos -16 yrs)62 None Outpatient or emergency department \nmedical attention: 4Moderate\nSiret -Alatrista 2010 † Unclear 53 None None Unclear\nSpiegel 2010 † Range 1 -56 yrs 150 None None Unclear\nUpton 2012 3-5 yrs:12\n6-9 yrs:24\n10-13 yrs:28\n14+ yrs:1075 None None Moderate\n60*Adapted from Murad MH et al, BMJ Evid Based Med 2018;23(2):60 -62.  Domains assessed included Selection, Ascertainment, \nCausality (excluding items pertaining to alternative causes and dose -response effect), and Reporting\n†Abstract only.\n3c. Summary of Studies and Outcomes —LAIV\nAuthor \nPublication yearAge/other \ncharacteristicsN Comparator Events by outcome Methodological \nquality concern*\nDes Roches 2015 2-16 yrs 68 Non -allergic group None Low\nTurner 2015a Median 4.9 yrs\n(2-17 yrs)282 None Cardiovascular symptoms, respiratory \nsymptoms, angioedema, or generalized \nurticaria: 6Low\nTurner 2015b Median 5.3 yrs\n(2-18 yrs)779 None Cardiovascular symptoms, respiratory \nsymptoms, angioedema, or generalized \nurticaria: 4Low\n61*Adapted from Murad MH et al, BMJ Evid Based Med 2018;23(2):60 -62.  Domains assessed included Selection, Ascertainment, \nCausality (excluding items pertaining to alternative causes and dose -response effect), and Reporting\n†Abstract only.\nCertainty Assessment\nImpact Certainty ImportanceNo. of \nstudiesStudy \nDesignMethod -\nological \nQuality*Inconsistency Indirectness ImprecisionOther \nconsiderations\n17Observa -\ntionalSeriousaNot serious SeriousbSeriouscNone0/1591 (0%) \ninstancesVery Low CRITICAL1. Death\n17Observa -\ntionalSeriousaNot serious SeriousbSeriouscNone0/1591 (0%) \ninstancesVery Low CRITICAL\n17Observa -\ntionalSeriousaNot serious SeriousbSeriouscNone0/1591 (0%) \ninstancesVery Low CRITICAL2. Anaphylaxis\n*Adapted from Murad MH et al, Methodological quality and synthesis of case series and case reports, BMJ Evid Based Med 2018;23(2):60 -62 [51].  Domains assesse d included Selection, \nAscertainment, Causality (excluding items pertaining to alternative causes and dose -response effect), and Reporting.\na. All are cohort studies without comparator interventions, with the exception of one randomized study which compared adminis tration of full dose vs split dose.  Full dose and split dose \nadministration are treated as equivalent in this review, and so this study is treated as a cohort study. Six of 17 are of unc lear methodological quality. Six of 17 are abstracts. \nb. Most studies did not report data specifically for persons with a history of anaphylaxis to egg.\nc. Cannot assess imprecision as these are proportions with no confidence intervals. However, some degree of imprecision shoul d be assumed.3. Allergic reaction symptoms requiring hospitalization4a: Seasonal IIV administered full -or split -dose, egg allergy of all severities (1)\n62\nCertainty Assessment\nImpactCertaint\nyImportanceNo. of \nstudiesStudy \nDesignMethod -\nological \nQuality*Inconsistency Indirectness ImprecisionOther \nconsiderations\n17Observa -\ntionalSeriousaNot serious SeriousbSeriouscNone3/1591 (0.2%) \ninstancesVery Low IMPORTANT4. Allergic reaction symptoms requiring outpatient or emergency department medical attention\n17Observa -\ntionalSeriousaNot Serious SeriousbSeriouscNone5/15 91 (0.3%)† \ninstancesVery Low IMPORTANT5. Allergic reaction including cardiovascular symptoms, respiratory symptoms, angioedema, or generalized urticaria \n*Adapted from Murad MH et al, Methodological quality and synthesis of case series and case reports, BMJ Evid Based Med 2018;23(2):60 -62 [51].  Domains assesse d \nincluded Selection, Ascertainment, Causality (excluding items pertaining to alternative causes and dose -response effect), and Re porting.\n† One study reported 6 instances of reactions included “wheezing, eczema exacerbation, or hives on chest”, but not specifying number with each symptom.  These are \nexcluded here.  If assumed that all six included wheezing, frequency would be 10/1591=0.6% \na. All are cohort studies without comparator interventions, with the exception of one randomized study which compared adminis tration of full dose vs split dose.  Full \ndose and split dose administration are treated as equivalent in this review, and so this study is treated as a cohort study. Sixof 17 are of unclear methodological \nquality. Six of 17 are abstracts. \nb. Most studies did not report data specifically for persons with a history of anaphylaxis to egg.\nc. Cannot assess imprecision as these are proportions with no confidence intervals. However, some degree of imprecision shoul d be assumed.4a: Seasonal IIV administered full -or split -dose, egg allergy of all severities (2)\n63\nCertainty Assessment\nImpact Certainty ImportanceNo. of \nstudiesStudy \nDesignMethod -\nological \nQuality*Inconsistency Indirectness ImprecisionOther \nconsiderations\n10a Observa -\ntionalSeriousbNot serious Not serious SeriouscNone0/322 (0%) \ninstancesVery Low CRITICAL1. Death\n10a Observa -\ntionalSeriousbNot serious Not seriousbSeriouscNone0/322 (0%) \ninstancesVery Low CRITICAL\n10a Observa -\ntionalSeriousbNot serious Not serious SeriouscNone0/322 (0%) \ninstancesVery Low CRITICAL2. Anaphylaxis\n3. Allergic reaction symptoms requiring hospitalization\n*Adapted from Murad MH et al, Methodological quality and synthesis of case series and case reports, BMJ Evid Based Med 2018;23(2):60 -62 [51].  Domains assesse d included Selection, \nAscertainment, Causality (excluding items pertaining to alternative causes and dose -response effect), and Reporting\na. Includes only studies which explicitly mentioned inclusion of egg -anaphylactic patients for whom data are specifically report ed.\nb. All are cohort studies without comparator intervention groups, including administration via either full dose or split -dose (2 -step) protocols. Two of 10 studies are abstracts, and 3 of 10 have \nuncertain methodological quality. \nc. Cannot assess imprecision as these are proportions with no confidence intervals. However, some degree of imprecision shoul d be assumed. \nd. Studies removed from denominator which included persons with a history of anaphylaxis to egg and reported event(s), but wh ichdid not indicate whether these occurred in a person with a \nhistory of anaphylaxis to egg. 4b: Seasonal IIV administered full -or split -dose, persons with anaphylaxis to egg (1)\n64\nCertainty Assessment\nImpactCertaint\nyImportanceNo. of \nstudiesStudy \nDesignMethod -\nological \nQuality*Inconsistency Indirectness ImprecisionOther \nconsiderations\n9a Observa -\ntionalSeriousbNot serious Not serious SeriouscNone0/295 (0%) \ninstancesdVery Low IMPORTANT4. Allergic reaction symptoms requiring outpatient or emergency department medical attention\n*Adapted from Murad MH et al, Methodological quality and synthesis of case series and case reports, BMJ Evid Based Med 2018;23(2):60 -62 [51].  Domains assesse d included Selection, \nAscertainment, Causality (excluding items pertaining to alternative causes and dose -response effect), and Reporting\na. Includes only studies which explicitly mentioned inclusion of egg -anaphylactic patients for whom data are specifically report ed.\nb. All are cohort studies without comparator intervention groups, including administration via either full dose or split -dose (2 -step) protocols. Two of 10 studies are abstracts, and 3 of 10 have \nuncertain methodological quality. \nc. Cannot assess imprecision as these are proportions with no confidence intervals. However, some degree of imprecision shoul d be assumed. \nd. Studies removed from denominator which included persons with a history of anaphylaxis to egg and reported event(s), but wh ichdid not indicate whether these occurred in a person with a \nhistory of anaphylaxis to egg.  8a Observa -\ntionalSeriousbNot serious Not serious SeriouscNone0/291 (0%)\ninstancesdVery Low IMPORTANT5. Allergic reaction including cardiovascular symptoms, respiratory symptoms, angioedema, or generalized urticaria 4b: Seasonal IIV administered full -or split -dose, persons with anaphylaxis to egg (2)\n65\n4c: Monovalent IIV administered full -or split -dose, egg allergy of all severities (1)\nCertainty Assessment\nImpact Certainty ImportanceNo. of \nstudiesStudy \nDesignMethod -\nological \nQuality*Inconsistency Indirectness ImprecisionOther \nconsiderations\n13Observa -\ntionalVery \nseriousa Not serious SeriousbSeriouscNone0/5235 (0%) \ninstancesVery Low CRITICAL1. Death\n13Observa -\ntionalVery \nseriousa Not serious SeriousbSeriouscNone0/5235 (0%) \ninstances dVery Low CRITICAL\n13Observa -\ntionalVery \nseriousa Not serious SeriousbSeriouscNone0/5235 (0%)\ninstancesVery Low CRITICAL2. Anaphylaxis\n3. Allergic reaction symptoms requiring hospitalization\n*Adapted from Murad MH et al, Methodological quality and synthesis of case series and case reports, BMJ Evid Based Med 2018;23(2):60 -62 [51].  Domains assesse d included Selection, \nAscertainment, Causality (excluding items pertaining to alternative causes and dose -response effect), and Reporting.\na. All were cohort studies without comparator intervention groups, including administration via either full dose or split -dose ( 2-step) protocols. Concerns regarding methodological quality were \n\"Low\" for only two studies, moderate for 6, and unclear for 4.  History of egg allergy was by self report only for the larges t study (n=3640).\nb. Most studies did not report data specifically for persons with a history of anaphylaxis to egg.\nc. Cannot assess imprecision as these are proportions without confidence intervals; however some degree of imprecision must b e assumed.\nd. One instance of Brighton Level 1 anaphylaxis was reported in a VAERS surveillance data summary from the 2009 -10 influenza sea son. This instance is not represented in the table as no \ndenominator is available for this paper. However, it was reported that 127,075,320 doses of monovalent influenza vaccine were distributed in the United States for the season. 66\nCertainty Assessment\nImpactCertaint\nyImportanceNo. of \nstudiesStudy \nDesignMethod -\nological \nQuality*Inconsistency Indirectness ImprecisionOther \nconsiderations\n13Observa -\ntionalVery \nseriousa Not serious SeriousbSeriouscNone77/5235 (1.5%) \ninstancesVery Low IMPORTANT4. Allergic reaction symptoms requiring outpatient or emergency department medical attention\n13Observa -\ntionalSeriousaNot serious SeriousbSeriouscNone33/5235 (0.6%) \ninstancesVery Low IMPORTANT5. Allergic reaction including cardiovascular symptoms, respiratory symptoms, angioedema, or generalized urticaria \n*Adapted from Murad MH et al, Methodological quality and synthesis of case series and case reports, BMJ Evid Based Med 2018;23(2):60 -62 [51].  Domains assesse d included Selection, \nAscertainment, Causality (excluding items pertaining to alternative causes and dose -response effect), and Reporting.\na. All were cohort studies without comparator intervention groups, including administration via either full dose or split -dose ( 2-step) protocols. Concerns regarding methodological quality were \n\"Low\" for only two studies, moderate for 6, and unclear for 4.\nb. Only 143 of total participants reported to have a history of anaphylaxis to egg. \nc. Cannot assess imprecision as these are proportions without confidence intervals; however some degree of imprecision must b e assumed.\nd. One instance of Brighton Level 1 anaphylaxis was reported in a VAERS surveillance data summary from the 2009 -10 influenza sea son. This instance is not represented in the table as no \ndenominator is available for this paper. However, it was reported that 127,075,320 doses of monovalent influenza vaccine were distributed in the United States for the season. 4c: Monovalent IIV administered full -or split -dose, egg allergy of all severities (2)\n67\n4d: Monovalent IIV administered full -or split -dose, persons with anaphylaxis to egg (1)\nCertainty Assessment\nImpact Certainty ImportanceNo. of \nstudiesStudy \nDesignMethod -\nological \nQuality*Inconsistency Indirectness ImprecisionOther \nconsiderations\n3Observa -\ntionalVery \nSeriousa Not Serious Not Serious SeriousbNone0/68 (0%)\nInstancesVery Low CRITICAL1. Death\n3Observa -\ntionalVery \nSeriousa Not Serious Not Serious SeriousbNone 0/68 instances Very Low CRITICAL\n3Observa -\ntionalVery \nSeriousa Not Serious Not Serious SeriousbNone 0/68 instances Very Low CRITICAL2. Anaphylaxis\n3. Allergic reaction symptoms requiring hospitalization\n*Adapted from Murad MH et al, Methodological quality and synthesis of case series and case reports, BMJ Evid Based Med 2018;23(2):60 -62 [51].  Domains assesse d included Selection, \nAscertainment, Causality (excluding items pertaining to alternative causes and dose -response effect), and Reporting.\na. Cohort studies without comparator intervention groups, including administration via either full dose or split -dose (2 -step) p rotocols.\nb. Cannot assess imprecision as these are proportions with no confidence intervals. However, some degree of imprecision shoul d be assumed.68\nCertainty Assessment\nImpactCertaint\nyImportanceNo. of \nstudiesStudy \nDesignMethod -\nological \nQuality*Inconsistency Indirectness ImprecisionOther \nconsiderations\n3Observa -\ntionalVery \nSeriousa Not Serious Not Serious SeriousbNone 0/68 instances Very Low IMPORTANT4. Allergic reaction symptoms requiring outpatient or emergency department medical attention\n3Observa -\ntionalVery \nSeriousa Not Serious Not Serious SeriousbNone 0/68 instances Very Low IMPORTANT5. Allergic reaction including cardiovascular symptoms, respiratory symptoms, angioedema, or generalized urticaria \n*Adapted from Murad MH et al, Methodological quality and synthesis of case series and case reports, BMJ Evid Based Med 2018;23(2):60 -62 [51].  Domains assesse d included Selection, \nAscertainment, Causality (excluding items pertaining to alternative causes and dose -response effect), and Reporting.\na. Cohort studies without comparator intervention groups, including administration via either full dose or split -dose (2 -step) p rotocols.\nb. Cannot assess imprecision as these are proportions with no confidence intervals. However, some degree of imprecision shoul d be assumed.4d: Monovalent IIV administered full -or split -dose, persons with anaphylaxis to egg (2)\n69\n4e. Seasonal LAIV, egg allergy of all severities (1)\nCertainty Assessment\nImpact Certainty ImportanceNo. of \nstudiesStudy \nDesignMethod -\nological \nQuality*Inconsistency Indirectness ImprecisionOther \nconsiderations\n3Observa -\ntionalSeriousaNot serious SeriousbSeriouscNone 0/1129 instances Very Low CRITICAL1. Death\n3Observa -\ntionalSeriousaNot serious SeriousbSeriouscNone 0/1129 instances Very Low CRITICAL\n3Observa -\ntionalSeriousaNot serious SeriousbSeriouscNone 0/1129 instances Very Low CRITICAL2. Anaphylaxis\n3. Allergic reaction symptoms requiring hospitalization\n*Adapted from Murad MH et al, Methodological quality and synthesis of case series and case reports, BMJ Evid Based Med 2018;23(2):60 -62 [51].  Domains assesse d included Selection, \nAscertainment, Causality (excluding items pertaining to alternative causes and dose -response effect), and Reporting.\na. All are cohort studies without a comparison intervention.\nb. Most studies did not report data specifically for persons with a history of anaphylaxis to egg.\nc. Cannot assess imprecision as these are proportions with no confidence intervals. However, some degree of imprecision shoul d be assumed.70\nCertainty Assessment\nImpactCertaint\nyImportanceNo. of \nstudiesStudy \nDesignMethod -\nological \nQuality*Inconsistency Indirectness ImprecisionOther \nconsiderations\n3Observa -\ntionalSeriousaNot serious SeriousbSeriouscNone 0/1129 instances Very Low IMPORTANT4. Allergic reaction symptoms requiring outpatient or emergency department medical attention\n3Observa -\ntionalSeriousaNot serious SeriousbSeriouscNone10/1129 (0.8%) \ninstancesVery Low IMPORTANT5. Allergic reaction including cardiovascular symptoms, respiratory symptoms, angioedema, or generalized urticaria \n*Adapted from Murad MH et al, Methodological quality and synthesis of case series and case reports, BMJ Evid Based Med 2018;23(2):60 -62 [51].  Domains assesse d included Selection, \nAscertainment, Causality (excluding items pertaining to alternative causes and dose -response effect), and Reporting.\na. All are cohort studies without a comparison intervention.\nb. Majority of persons in each study did not have history of anaphylaxis to egg. \nc. Cannot assess imprecision as these are proportions with no confidence intervals. However, some degree of imprecision shoul d be assumed.4e. Seasonal LAIV, egg allergy of all severities (2)\n71\nCertainty Assessment\nImpact Certainty ImportanceNo. of \nstudiesStudy \nDesignMethod -\nological \nQuality*Inconsistency Indirectness ImprecisionOther \nconsiderations\n3Observa -\ntionalSeriousaNot serious Not serious SeriousbNone 0/412 instances Very Low CRITICAL1. Death\n3Observa -\ntionalSeriousaNot serious Not serious SeriousbNone 0/412 instances Very Low CRITICAL\n3Observa -\ntionalSeriousaNot serious Not serious SeriousbNone 0/412 instances Very Low CRITICAL2. Anaphylaxis\n3. Allergic reaction symptoms requiring hospitalization\n*Adapted from Murad MH et al, Methodological quality and synthesis of case series and case reports, BMJ Evid Based Med 2018;23(2):60 -62 [51].  Domains assesse d included Selection, \nAscertainment, Causality (excluding items pertaining to alternative causes and dose -response effect), and Reporting.\na. All are cohort studies with no comparison groups.\nb. Cannot assess imprecision as these are proportions with no confidence intervals. However, some degree of imprecision shoul d be assumed.\nc. Cannot assess imprecision as these are proportions with no confidence intervals. However, some degree of imprecision shoul d be assumed. Very low denominator count. 4f. Seasonal LAIV, persons with anaphylaxis to egg (1)\n72\nCertainty Assessment\nImpact Certainty ImportanceNo. of \nstudiesStudy \nDesignMethod -\nological \nQuality*Inconsistency Indirectness ImprecisionOther \nconsiderations\n3Observa -\ntionalSeriousaNot serious Not serious SeriousbNone 0/412 instances Very Low IMPORTANT4. Allergic reaction symptoms requiring outpatient or emergency department medical attention\n1Observa -\ntionalSeriousaNot serious Not seriousVery \nseriousc None 0/27 instances Very Low IMPORTANT5. Allergic reaction including cardiovascular symptoms, respiratory symptoms, angioedema, or generalized urticaria \n*Adapted from Murad MH et al, Methodological quality and synthesis of case series and case reports, BMJ Evid Based Med 2018;23(2):60 -62 [51].  Domains assesse d included Selection, \nAscertainment, Causality (excluding items pertaining to alternative causes and dose -response effect), and Reporting.\na. All are cohort studies with no comparison groups.\nb. Cannot assess imprecision as these are proportions with no confidence intervals. However, some degree of imprecision shoul d be assumed.\nc. Cannot assess imprecision as these are proportions with no confidence intervals. However, some degree of imprecision shoul d be assumed. Very low denominator count. \nd. Studies removed from denominator which included persons with a history of anaphylaxis to egg and reported event(s), but which did not indicate whether these occurred in a person with a \nhistory of anaphylaxis to egg. 4f. Seasonal LAIV, persons with anaphylaxis to egg (2)\n73\nAppendix 1.  Event Summary: Death\nAuthor \nPublication yearAge N egg allergic N anaphylaxis to egg Events\nNo studies reported this outcome.\n74\nAppendix 2. Event Summary: Anaphylaxis\nAuthor \nPublication yearAge N egg allergic N anaphylaxis to egg Events\nNo studies reported this outcome.\n75\nAppendix 3. Event Summary: Hospitalization\nAuthor \nPublication yearAge N egg allergic N anaphylaxis to egg Events\nNo studies reported this outcome.\n76\nAppendix 4. Event Summary: Outpatient/Emergency Care (1)\nAuthor \nPublication yearAge Vaccine N egg allergic N anaphylaxis to \neggEvents\nEsposito 2008 Mean 6.03 +/ -3.33 Seasonal \nvirosomal44 11 •1 bronchospasm in mildly \nallergic child, treated with \nbronchodilator and \nsteroid.\nJames 1998 Mean 6.25 \n(10mos -16.5 years)Seasonal IIV 83 27 •1 delayed (>1 hour post -\nvaccination) emesis, mild \ncough, wheeze treated \nwith nebulizer.*\n•1 delayed (>1 hour post -\nvaccination) erythema at \ninjection site treated.*\n*Uncertain whether occurred in individual with anaphylaxis to egg.\n77\nAuthor \nPublication yearAge Vaccine N egg allergic N anaphylaxis to \negg/severe allergyEvents\nForsdahl 2012 Mean 6.25 yrs\n(10 mos -16.5 yrs)Monovalent IIV 80 19 •1 wheal on lip, diffuse \nrash, and loose stools a \nfew minutes after 90% \nstep; treated with \nantihistamine.\nGagnon 2010 -1 173 <2 yrs\n280 2 -4 yrs\n277 5 -11 yrs\n100 ≥12 yrsMonovalent IIV 830 - •1 wheeze treated with \nbronchodilator.\n•1 hives treated with \nantihistamines\n•1 ocular pruritis treated \nwith antihistamines\n•1 angioedema treated \nwith antihistamines.Appendix 4. Event Summary: Outpatient/Emergency Care (2)\n78\nAuthor \nPublication yearAge Vaccine N egg allergic N anaphylaxis to \negg/severe allergyEvents\nGagnon 2010 -2 Not provided Monovalent IIV 3460 - •1 mouth/throat tingling 10 -15 min \npost -vaccination; received two \ndoses epinephrine and observed in \nemergency department; recovered.\n•1 continuous crying with wheezing \n30 min post -vaccination.  Received \nepinephrine and bronchodilator (6 \ntreatments), observed 4 hours, \nrecovered. \n•66 skin and respiratory symptoms, \ntreated with antihistamines\n•42 with skin involvement\n•17 with throat \ntingling/tightening\n•7 with cough (4 also treated \nwith bronchodilator)Appendix 4. Event Summary: Outpatient/Emergency Care (3)\n79\nAuthor \nPublication yearAge Vaccine N egg \nallergicN anaphylaxis to \negg/severe allergyEvents\nSchuler 2011 Mean 4.5 yrs \n(10 mos -16 yrs)Monovalent IIV 62 - •1 vasovagal response requiring \nsymptomatic management.\n•1 hyporesponsive episode; \nreferred to emergency \ndepartment.\n•2 hives treated with \nantihistamines.Appendix 4. Event Summary: Outpatient/Emergency Care (4)\n80\nAuthor \nPublication yearAge Vaccine N egg allergic N anaphylaxis \nto egg/severe \nallergyEvents\nErlewyn -\nLajeunesse 2010 Children Seasonal IIV 16 doses 4 •1 instance subjective wheeze*\nEsposito 2008 Mean 6.03 +/ -3.33 Seasonal IIV 44 11 •1 instance bronchospasm in mildly \nallergic child, treated with \nbronchodilator and steroid.\nJames 1998 Mean 6.25 \n(10mos -16.5 years)Seasonal IIV 83 27 •1 with mild throat itching, cough, \nand wheeze.*\n•1 delayed (>1 hour post -vaccination) \nemesis, mild cough, wheeze treated \nwith nebulizer.*\n•1 mild URI symptoms.*\n*Uncertain whether occurred in individual with anaphylaxis to egg.Appendix 5.  Event Summary: Cardiovascular, Respiratory, Angioedema, or \nGeneralized Urticaria (1)\n81\nAuthor \nPublication yearAge Vaccine N egg allergic N anaphylaxis to \negg/severe allergyEvents\nForsdahl 2012 Mean 6.25 yrs\n(10 mos -16.5 yrs)Monovalent IIV 80 19 •1 sneezing without \nbronchospasm.\nGagnon 2010 -1 173 <2 yrs\n280 2 -4 yrs\n277 5 -11 yrs\n100 ≥12 yrsMonovalent IIV 830 - •1 sensation of throat \nclosure\n•1 hoarse voice\n•1 angioedema\n•1 bilateral wheeze\n•2 generalized urticariaAppendix 5.  Event Summary: Cardiovascular, Respiratory, Angioedema, or \nGeneralized Urticaria (2)\n82\nAuthor \nPublication yearAge Vaccine N egg allergic N anaphylaxis to \negg/severe allergyEvents\nGagnon 2010 -2 Not provided Monovalent IIV 3460 - •1 mouth/throat tingling 10 -15 \nmin post -vaccination; \nreceived two doses \nepinephrine and observed in \nemergency department; \nrecovered.\n•1 continuous crying with \nwheezing 30 min post -\nvaccination.  Received \nepinephrine and \nbronchodilator (6 treatments), \nobserved 4 hours, recovered. \n•17 with throat \ntingling/tightening\n•7 with cough (4 also treated \nwith bronchodilator)Appendix 5.  Event Summary: Cardiovascular, Respiratory, Angioedema, or \nGeneralized Urticaria (3)\n83\nAuthor \nPublication yearAge Vaccine N egg allergic N anaphylaxis to \negg/severe allergyEvents\nTurner 2015a Median 4.9 yrs\n(2-17 yrs)LAIV3 282 115 •6 rhinitis within 30 min post -\nvaccination.\nTurner 2015b Median 5.3 yrs\n(2-18 yrs)LAIV4 779 157 •4 rhinitis within 2 hours post -\nvaccination.Appendix 5.  Event Summary: Cardiovascular, Respiratory, Angioedema, or \nGeneralized Urticaria (4)\n84\nSummary of Evidence for Outcomes of Interest\nOutcome Importance Included in profile Certainty\nDeath Critical Yes Very low\nAnaphylaxis Critical Yes Very low\nAllergic reaction symptoms requiring hospitalization Critical Yes Very low\nAllergic reaction symptoms requiring outpatient or \nemergency department medical attentionImportant Yes Very low\nAllergic reaction including cardiovascular symptoms, \nrespiratory symptoms, angioedema, or generalized \nurticariaImportant Yes Very low\n85\n1. Anvari , S., et al., Influenza vaccine testing and administration in Egg allergic children. Journal of Investigative Medicine, 2011. 59(2): p. 477 -478.\n2. Chan D. The safety of influenza vaccination in children with anaphylactic egg allergy. Internal Medicine Journal 2009; 39 (Suppl. 5): A139.\n3. Chung, E.Y ., L. Huang, and L. Schneider, Safety of influenza vaccine administration in egg -allergic patients. Pediatrics, 201 0. 125(5): p. e1024 -30.\n4. Comeau, J., et al., Why is Australian policy still cautious with influenza vaccination in severe egg allergic children? In ternal Medicine Journal, 2016. 46 (Supplement 4): p. 6.\n5. Des Roches, A., et al., Egg -allergic patients can be safely vaccinated against influenza. Journal of Allergy & Clinical Immun ology, 2012. 130(5): p. 1213 -1216.e1.\n6. Des Roches, A., et al., Safe vaccination of patients with egg allergy by using live attenuated influenza vaccine. The Jour nalof Allergy & Clinical Immunology in Practice, 2015. \n3(1): p. 138 -9.\n7. Didenko , I., et al., Influenza A (H1N1) vaccination in individuals with egg allergy. Revista Portuguesa de Imunoalergologia , 2010. 18(3): p. 243 -252.\n8. Dona, D., et al., Special immunization service: A 14 -year experience in Italy. PLoS ONE, 2018. 13 (4) (no pagination)(e0195881).\n9. Dorsey MJ.  Influenza vaccine in 55 patients with egg allergy.  J Allg Clin Immunol 2005: S250.\n10. Erlewyn -Lajeunesse , M., et al., Multicentre audit of influenza immunisation in children allergic to egg. Allergy: European Journal of Allergy and Clinical Immunology, 2010. \n92): p. 364 -365.\n11. Esposito, S., et al., Safe administration of an inactivated virosomal adjuvanted influenza vaccine in asthmatic children with egg allergy. Vaccine, 2008. 26(36): p. 4664 -8.\n12. Forsdahl , B.A., Reactions of Norwegian children with severe egg allergy to an egg -containing influenza A (H1N1) vaccine: a retrospective audit. BMJ Open, 2012. 2: p. \ne000186.\n13. Fung, I. and J.M. Spergel , Administration of influenza vaccine to pediatric patients with egg -induced anaphylaxis. Journal of Allergy & Clinical Immunolo gy, 2012. 129(4): p. \n1157 -9.\n14. Gagnon, R., et al., Safe vaccination of patients with egg allergy with an adjuvanted pandemic H1N1 vaccine. Journal of Al lergy & Clinical Immunology, 2010. 126(2): p. 317 -\n23.\n15. Grainger -Allen, E., et al., Safety of influenza immunisation in high risk egg allergy. Clinical and Experimental Allergy, 2013. 43 (12): p. 1433.\n16. Greenhawt , M.J., et al., Safe administration of the seasonal trivalent influenza vaccine to children with severe egg allergy. Annals o f Allergy, Asthma, & Immunology, 2012. \n109(6): p. 426 -30.References\n17. Greenhawt , M.J., et al., The safety of the H1N1 influenza A vaccine in egg allergic individuals. Annals of Allergy, Asthma, & Immunolo gy,2010. 105(5): p. 387 -93.\n18. Halsey, N.A., et al., Immediate hypersensitivity reactions following monovalent 2009 pandemic influenza A (H1N1) vaccines : Reports to VAERS. Vaccine, 2013. 31(51): p. \n6107 -6112.\n19. Hotte SL. A 6 -year Experience with Influenza Vaccination in Egg Allergic Patients. J Allerg Clin Immunol 2008;121:s239.\n20. Howe, L.E., et al., Safe administration of seasonal influenza vaccine to children with egg allergy of all severities. Ann alsof Allergy, Asthma, & Immunology, 2011. 106(5): p. \n446-7.\n21. James, J.M., et al., Safe administration of influenza vaccine to patients with egg allergy. Journal of Pediatrics, 1998. 133(5): p. 624 -8.\n22. Kawahara, H., et al., [Immediate adverse reactions after administration of the influenza vaccine to patients with positiv e CAP-RAST to egg white]. Arerugi -Japanese \nJournal of Allergology, 2002. 51(7): p. 559 -64.\n23. Kawahara, H., et al., [Safe administration of influenza vaccine in asthmatic children]. Arerugi -Japanese Journal of Allergology, 1998. 47(7): p. 679 -86.\n24. Khan, F.S., et al., Influenza vaccine administration in egg allergic children. Journal of Allergy and Clinical Immunology , 2012. 1): p. AB70.\n25. Kletz , M.R., et al., Administration of egg -derived vaccines in patients with history of egg sensitivity. Annals of Allergy, 1990. 64( 6): p. 527 -9.\n26. Leo, S.H., J. Dean, and E.S. Chan, Safety of H1N1 and seasonal influenza vaccines in egg allergic patients in British Col umb ia. Allergy, Asthma and Clinical Immunology. \nConference: Canadian Society of Allergy and Clinical Immunology Annual Scientific Meeting, 2010. 6(SUPPL. 2).\n27. Murad, M.H., et al., Methodological quality and synthesis of case series and case reports. BMJ Evid Based Med, 2018. 23(2 ): p. 60 -63.\n28. Murphy, K.R. and R.C. Strunk, Safe administration of influenza vaccine in asthmatic children hypersensitive to egg protei ns.Journal of Pediatrics, 1985. 106(6): p. 931 -3.\n29. Nickolls , C., et al., The safety of H1N1/seasonal influenza vaccination in egg allergic children -A prospective study. Internal Medicin e Journal, 2010. 4): p. 16.\n30. Owens, G. and A. MacGinnitie , Higher -ovalbumin -content influenza vaccines are well tolerated in children with egg allergy. Journal of Allergy & Clinical Imm unology, 2011. \n127(1): p. 264 -5.\n31. Park, A., et al. Administration of influenza vaccine to patients with egg allergy. J Allergy Clin Immunol , 2008 (Februar y).p. S240.\n32. Paschall, V.L., et al., Do egg -specific IgElevels predict reactions to seasonal influenza or H1N1 vaccination? Journal of Allergy and Clinical Immunology, 2011. 1): p. AB182.\n33. Pien , G.C., et al., Coordination of multidisciplinary resources for vaccination of egg -allergic individuals during an H1N1 (novel) i nfluenza pandemic. Allergy & Asthma \nProceedings, 2010. 31(6): p. 507 -10.\n34. Pitt, T., et al., Assessment of epicutaneous testing of a monovalent Influenza A (H1N1) 2009 vaccine in egg allergic patients. Allergy, Asthma, & Clinical Immunology : \nOfficial Journal of the Canadian Society of Allergy & Clinical Immunology, 2011. 7(1): p. 3.\n35. Schuler, J.E., et al., Administration of the adjuvanted pH1N1 vaccine in egg -allergic children at high risk for influenza A/ H1N1 disease. Can J Public Health, 2011. 102(3): p. \n196-9.\n36. Seyerle , J., R. Scherzer, and E.A. Erwin, Testing and administration of seasonal and pandemic influenza vaccines in egg allergic pat ients. Annals of Allergy, Asthma and \nImmunology, 2010. 105 (5): p. A109.\n37. Shimizu, M., et al., [Safety of Influenza Vaccination in Children with Severe Allergy to Hen's Eggs: A Prospective Case S eries Study]. Arerugi -Japanese Journal of \nAllergology, 2016. 65(2): p. 128 -33.\n38. Siret -Alatrista , A., et al., The 2009 -2010 H1N1 vaccination campaign for patients with egg allergy in a region of France. Allergy, 2011. 66(2): p. 298 -9.\n39. Spiegel, W. and R. Anolik , Administration of H1N1 vaccine in an eggallergic population. Annals of Allergy, Asthma and Immunology, 2010. 105 (5): p. A4.\n40. Thanik , E.S., A.L. Cox, and H.A. Sampson, Administration of a low egg -containing influenza vaccine [ fluarix ] in an egg -alphallergic pediatric population. Journal of Allergy \nand Clinical Immunology, 2010. 1): p. AB25.\n41. Tounian , P ., et al., [Vaccinations of children allergic to eggs with vaccine prepared with egg]. Archives Francaises de Pediatrie , 1993. 50(3): p. 191 -5.\n42. Tozandehjani , S., et al., Safety of Inactivated Influenza Vaccine in Patients with Egg Allergy in Kurdistan Province, Iran. Iranian Journ al of Public Health, 2019. 48(4): p. 758 -\n763.\n43. Turner, P .J., et al., Safety of live attenuated influenza vaccine in atopic children with egg allergy. Journal of Allergy & Clinical Immunology, 2015. 136(2): p. 376 -81.\n44. Turner, P .J., et al., Safety of live attenuated influenza vaccine in young people with egg allergy: multicentre prospective cohort study. BMJ, 2015. 351: p. h6291.\n45. Upton, J.E., et al., No systemic reactions to influenza vaccination in egg -sensitized tertiary -care pediatric patients. Alle rgy, Asthma, & Clinical Immunology : Official Journal \nof the Canadian Society of Allergy & Clinical Immunology, 2012. 8: p. 2.\n46. Webb, L., et al., Single -dose influenza vaccination of patients with egg allergy in a multicenter study. Journal of Allergy & Clinical Immunology, 2011. 128(1): p. 218 -9.\n47. Woo, E.J., Allergic reactions after egg -free recombinant influenza vaccine: reports to the US Vaccine Adverse Event Reportin g System. Clinical Infectious Diseases, 2015. \n60(5): p. 777 -80.\n48. Woo, E.J., et al., Postmarketing safety surveillance of trivalent recombinant influenza vaccine: Reports to the Vaccine Adverse Event Reporting System. Vaccin e,2017. \n35(42): p. 5618 -5621.\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the \nofficial position of the Centers for Disease Control and Prevention.", "summary": "National Center for Immunization & Respiratory Diseases Influenza Vaccination of Persons with Egg Allergy: Evidence to Recommendations Discussion and Work Group Considerations Lenee H. Blanton Lisa A. Grohskopf Influenza Division, CDC/NCIRD Advisory Committee on Immunization Practices June 21, 2023 •Donna Hummell •Karen Broder •Pedro Moro •Geta Aynalem •Shashi Sharma •Elaine Miller •Andrew Leidner •Rebecca Morgan •Doug Campos -OutcaltAcknowledgements 2 Background •Affects approximately 1 -3%…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/02-influenza-grohskopf-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 89}
{"title": "03 influenza grohskopf 508", "content": "National Center for Immunization & Respiratory Diseases\nInfluenza Vaccine Safety Update and \nProposed Recommendations for the 2023 -24 Influenza Season\nLisa A. Grohskopf\nInfluenza Division, CDC/NCIRD\nAdvisory Committee on Immunization Practices\nJune 21, 2023\nInfluenza Division\n•Lenee Blanton\n•Jill Ferdinands\n•Lindsay Trujillo\n•Lynette Brammer\n•Alicia Budd\n•Jessie Chung\n•Brendan Flannery\n•Sinead Morris\n•Samantha Olson\n•Sascha Ellington\n•Carrie Reed\n•Mark Tenforde\n•Tim UyekiImmunization Safety Office\n•Geta Aynalem\n•Karen Broder\n•Pedro Moro\n•Elaine Miller\n•Shashi Sharma\n•David Shay\n•Tom Shimabukuro\nImmunization Services Division\n•Andrew Kroger\nCDC Library\n•Joanna TalianoCISA\n•Donna HummellAcknowledgements\nInfluenza Vaccine Safety Update\nVaccine Safety Update: 2022 -2023 Influenza Season \n▪~173 million doses of influenza vaccine distributed in United States* \n▪Vaccine Adverse Event Reporting System (VAERS) (co-managed by CDC and FDA) \n•No new safety concerns identified for influenza vaccines  \n▪Vaccine Safety Datalink (VSD) (collaboration between CDC and 9 integrated healthcare \norganizations)\n•~5.5 million doses of influenza vaccine administered in VSD\n•No new safety concerns identified in influenza vaccine monitoring** \n•Statistical signal for ischemic stroke after Pfizer -BioNTech bivalent mRNA COVID -19 vaccine in persons \naged ≥65 years detected in VSD analysis for COVID -19 vaccine safety monitoring, previously presented \nto ACIP***\n•Post -signal analysis in VSD found an elevated rate ratio for ischemic stroke after simultaneous vaccination with \nPfizer -BioNTech bivalent mRNA COVID -19 vaccine and high -dose or adjuvanted influenza vaccine, which has \nattenuated over time\n•Separate analyses did not detect an elevated rate ratio for ischemic stroke after influenza vaccine administered \nwithout bivalent mRNA COVID -19 vaccine\n4* Weekly Flu Vaccination Dashboard | FluVaxView | Seasonal Influenza (Flu) | CDC\n** Outcomes monitored in VSD: acute disseminated encephalomyelitis, anaphylaxis, Bell’s Palsy, encephalitis, Guillain -Barré syndrome, seizures, transverse myel itis \n*** Shimabukuro T, ACIP presentation on April 19, 2023 mRNA COVID -19 bivalent booster vaccine safety update (cdc.gov)\nOverview of Proposed Recommendations for \n2023 -24\n•Vaccination of all persons aged ≥6 months who do not have contraindications \ncontinues to be recommended.\n•Recommendations regarding timing of vaccination are unchanged from 2022 -23.\n•Changes include:\n–Updated U.S. influenza vaccine composition for 2023 -24.\n–Proposed changes to the recommendations for vaccination for persons with egg \nallergy.Overview of Proposed Recommendations\nTiming of Vaccination\n•Unchanged from last season.\n•For most persons who need only 1 dose of influenza vaccine for the season, \nvaccination should ideally be offered during September or October.\n•Vaccination should continue after October and throughout the influenza season as \nlong as influenza viruses are circulating and unexpired vaccine is available.\n•Vaccination during July and August are not recommended for most groups.\n•Considerations for July and August vaccination are noted for adults, children, and \npregnant persons.Timing of Influenza Vaccination\n•For most adults (particularly adults aged ≥65 years) and for pregnant persons in the \nfirst or second trimester, vaccination during July and August should be avoided \nunless there is concern that vaccination later in the season might not be possible.Timing of Influenza Vaccination —\nAdults and Pregnant Persons in First/Second Trimester\n•Children who require 2 doses: \n–Should receive their first dose as soon as possible (including during July and \nAugust, if vaccine is available) to allow the second dose (which must be \nadministered ≥4 weeks later) to be received, ideally, by the end of October.\n•Children who require only 1 dose: \n–Vaccination during July and August can be considered for children of any age \nwho need only 1 dose of influenza vaccine for the season . Timing of Influenza Vaccination —\nChildren\n•Vaccination during July and August can be considered because vaccination might \nreduce risk for influenza illness in their infants during the first months after birth, \nwhen they are too young to receive influenza vaccine.Timing of Influenza Vaccination —\nPregnant Persons in Third Trimester\nInfluenza Vaccine Composition for 2023 -24\n•All vaccines available in the U.S. are quadrivalent.\n•The 2023 -24 composition includes updated influenza A(H1N1)pdm09 components.\n•All U.S. -licensed influenza vaccines will include hemagglutinin derived from:\n–An influenza A/Victoria/4897/2022 (H1N1)pdm09-like virus (egg-based vaccines) \nAn influenza A /Wisconsin /67/2022 (H1N1)pdm09 -like virus (cell and recombinant vaccines)\n–An influenza A/Darwin/9/2021 (H3N2) -like virus (egg -based vaccines)\nAn influenza A /Darwin/6/2021 (H3N2) -like virus (cell and recombinant vaccines)\n–An influenza B/Austria/1359417/2021 -like virus (B/Victoria lineage)\n–An influenza B/Phuket/3073/2013 -like virus (B/Yamagata lineage)U.S. Influenza Vaccine Composition for 2023 -24\nVaccines and Related Biological Products Advisory Committee March 7, 2023 Meeting Announcement -03/07/2023 | FDA\nProposed Recommendations for Vaccination of \nPersons with Egg Allergy\n•All persons aged ≥6 months with egg allergy should receive influenza vaccine unless a \ncontraindication exists. Any influenza vaccine that is otherwise appropriate for the recipient’s age and \nhealth status can be used (egg based or non -egg based). \n•Egg allergy in and of itself necessitates no additional safety measures for influenza vaccination \nbeyond those recommended for any recipient of any vaccine, regardless of severity of previous \nreaction to egg.\n•Severe and life -threatening reactions to vaccines can rarely occur with any vaccine and in any vaccine \nrecipient, regardless of allergy history. Providers are reminded that all vaccines should be \nadministered in settings in which personnel and equipment needed for rapid recognition and \ntreatment of acute hypersensitivity reactions are available.  All vaccination providers should be \nfamiliar with their office emergency plan and be certified in cardiopulmonary resuscitation.Proposed Recommendations for Vaccination of \nPersons with Egg Allergy\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the \nofficial position of the Centers for Disease Control and Prevention.", "summary": "National Center for Immunization & Respiratory Diseases Influenza Vaccine Safety Update and  Proposed Recommendations for the 2023 -24 Influenza Season Lisa A. Grohskopf Influenza Division, CDC/NCIRD Advisory Committee on Immunization Practices June 21, 2023 Influenza Division •Lenee Blanton •Jill Ferdinands •Lindsay Trujillo •Lynette Brammer •Alicia Budd •Jessie Chung •Brendan Flannery •Sinead Morris •Samantha Olson •Sascha Ellington •Carrie Reed •Mark Tenforde •Tim UyekiImmunization Safety…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/03-influenza-grohskopf-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 16}
{"title": "01 Pneumococcal Poehling 508", "content": "Pneumococcal Vaccines\nKatherine A. Poehling, MD, MPH\nPneumococcal Vaccines Work Group Chair\nAdvisory Committee on Immunization Practices\nJune 22, 2023\nPneumococcal Vaccines Work Group\nACIP Members\n•Katherine Poehling (Chair)\n•Sarah Long \nEx Officio Members\n•Jeffrey Kelman  (CMS)\n•Lucia Lee            (FDA)\n•Tina Mongeau   (FDA)\n•Uzo Chukwuma (IHS)\n•Mamodikoe Makhene (NIH)\nCDC Lead\n•Miwako Kobayashi (NCIRD)Liaison Representatives and Consultants\n•Lynn Fisher                (AAFP)\n•Mark Sawyer             (AAP/COID)\n•Jason Goldman         (ACP)\n•David Nace                (AGS/AMDA)\n•Cora Hoover              (AIM)\n•Aleksandra Wierzbowski   (NACI)\n•James McAuley         (IDSA)\n•William Schaffner     (NFID)\n•Virginia Caine            (NMA)\n•Monica Farley           (VAMC/Emory)\n•Keith Klugman          (BMGF)\n•Arthur Reingold        (UC Berkley)\n•Lorry Rubin                (CCMC)\n•Richard Zimmerman (U. of Pittsburgh) \nPneumococcal Vaccines Work Group\nCDC Contributors\n•Adam Cohen           (Respiratory Diseases Branch)\n•Ryan Gierke             (Respiratory Diseases Branch)\n•Jennifer Farrar        (Respiratory Diseases Branch)\n•Diepreye Ayabina   (Division of Bacterial Diseases)\n•Pedro Moro             (Immunization Safety Office)\n•Andrew Leidner      (Immunization Services Division)\n•Liz Velazquez            (Immunization Services Division)\n•Marc Fischer            (Arctic Investigations Program)\n•Noele Nelson      (Division of Bacterial Diseases)\nGRADE/ EtR consultants\n•Doug Campos -Outcalt\n•Rebecca Morgan\nSerotypes contained in pneumococcal vaccines\nPneumococcal conjugate vaccine s (PCVs): PCV13, PCV15, PCV20\nPneumococcal  polysaccharide vaccine (PPSV): PPSV23\n•PCV15 non -PCV13 : serotypes 22F and 33F\n•PCV20 non -PCV15 : serotypes 8, 10A, 11A, 12F, and 15B\n•PPSV23 non -PCV20 : serotypes 2, 9N, 17F, and 201 3 4 5 6A 6B 7 F 9V 14 18\nC19\nA19\nF23\nF22\nF33\nF8 10\nA11\nA12\nF15\nB2 9N 17\nF20\nPCV13\nPCV15\nPCV20\nPPSV23\n4\nExtended indication for PCV20 use among children approved on \nApril 27, 2023\n2021 2022 2023\nPediatric  PCV20  use approved \nApril 2023\nPediatric  PCV15  use approved\nJune 2022PCV15  and PCV20  approved \nfor use  in adults in 2021\n\nBoth PCV15 and PCV20 were approved based on safety and \nimmunogenicity data compared with PCV13\n•No direct PCV15 vs PCV20 comparison\n•Unknown clinical implications:\n•Numerically lower antibody responses vs PCV13\n•Numerically higher antibody response against serotype 3 in PCV15 vs PCV13\nFebruary 2022, 2023 ACIP meeting presentations\nAll children under age 2 years have the same \npneumococcal vaccine recommendations\n•3 primary series and a booster=“3+1” schedule\n2 months\nPCV4 months\nPCV12–15 months\nPCV6 months\nPCV\nPrimary Series Booster\nCurrently, either PCV13  or PCV15  can be used\nChildren with certain underlying conditions are recommended \nto receive PPSV23 in addition to the recommended PCV doses\nUse of 15 -Valent Pneumococcal Conjugate Vaccine Among U.S. Children: Updated Recommendations of the Advisory Committee on Immuni zation \nPractices — United States, 2022 | MMWR (cdc.gov)PPSV23\nPPSV23 PPSV23\n≥8 weeks ≥5 years\nPPSV23CMC, CSF leak,\ncochlear \nimplant Recommended \nPCV doses\n≥8 weeks\nImmuno-\ncompromisedRecommended \nPCV doses\nCMC aged 6 –18 \nyears \nNote:  Excludes catch -up vaccination schedules.\nCMC=chronic medical conditions, including chronic heart disease, chronic lung disease, diabetes mellitus\nCSF=cerebrospinal fluid Recommended \nPCV dosesHealthy \nchildren\nCurrent Risk -Based Pneumococcal Vaccine Recommendations\nChildren Adults\nAlcoholism\nChronic heart disease\nChronic lung disease\nChronic liver disease\nCigarette smoking\nDiabetes mellitus\nCerebrospinal fluid leak\nCochlear implant\nChronic renal failure or nephrotic syndrome\nCongenital or acquired asplenia, or splenic \ndysfunction\nCongenital or acquired immunodeficiency\nDiseases and conditions treated with \nimmunosuppressive drugs or radiation therapy\nHIV infection\nSickle cell disease or other hemoglobinopathies\nSolid organ transplant•Children: Including asthma if treated with high -dose oral \ncorticosteroid therapy.\n•Adults: Includes chronic obstructive pulmonary disease, \nemphysema, and asthma.\n→ Should we expand the indication for asthma in children? \nCurrent Risk -Based Pneumococcal Vaccine Recommendations\nChildren Adults\nAlcoholism\nChronic heart disease\nChronic lung disease\nChronic liver disease\nCigarette smoking\nDiabetes mellitus\nCerebrospinal fluid leak\nCochlear implant\nChronic renal failure or nephrotic syndrome\nCongenital or acquired asplenia, or splenic \ndysfunction\nCongenital or acquired immunodeficiency\nDiseases and conditions treated with \nimmunosuppressive drugs or radiation therapy\nHIV infection\nSickle cell disease or other hemoglobinopathies\nSolid organ transplantShould we add “chronic liver disease” as part of pediatric \nrisk-based recommendation? \nCurrent Risk -Based Pneumococcal Vaccine Recommendations\nChildren Adults\nAlcoholism\nChronic heart disease\nChronic lung disease\nChronic liver disease\nCigarette smoking\nDiabetes mellitus\nCerebrospinal fluid leak\nCochlear implant\nChronic renal failure or nephrotic \nsyndrome\nCongenital or acquired asplenia, or splenic \ndysfunction\nCongenital or acquired immunodeficiency\nDiseases and conditions treated with \nimmunosuppressive drugs or radiation therapy\nHIV infection\nSickle cell disease or other hemoglobinopathies\nSolid organ transplantShould we expand the indication to those with stage 2 –5 \nchronic kidney disease? \nPolicy questions considered by the Work Group\n•Should PCV20  be recommended as an option for pneumococcal \nconjugate vaccination according to currently recommended dosing \nand schedules, for U.S. children aged <2 years ?\n•Should PCV20 without PPSV23 be recommended as an option for \npneumococcal vaccination for U.S. children aged 2 –18 years with \nunderlying medical conditions that increase the risk of \npneumococcal disease?\nToday’s Pneumococcal Vaccines session outline\nIntroduction Dr. Katherine Poehling \n(ACIP, WG Chair)\nEconomic analysis and public health impact of PCV20 \nuse in childrenDr. Charles Stoecker \n(Tulane University)\nComparison of cost -effectiveness analyses on PCV20 \nuse in childrenDr. Ayabina Diepreye \n(CDC/NCIRD)\nSummary of WG interpretation of EtR and policy \noptionsDr. Miwako Kobayashi \n(CDC/NCIRD)\nVFC resolution Dr. Jeanne Santoli\n(CDC/NCIRD)", "summary": "Pneumococcal Vaccines Katherine A. Poehling, MD, MPH Pneumococcal Vaccines Work Group Chair Advisory Committee on Immunization Practices June 22, 2023 Pneumococcal Vaccines Work Group ACIP Members •Katherine Poehling (Chair) •Sarah Long  Ex Officio Members •Jeffrey Kelman  (CMS) •Lucia Lee            (FDA) •Tina Mongeau   (FDA) •Uzo Chukwuma (IHS) •Mamodikoe Makhene (NIH) CDC Lead •Miwako Kobayashi (NCIRD)Liaison Representatives and Consultants •Lynn Fisher                (AAFP) •Mark…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/01-Pneumococcal-Poehling-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 13}
{"title": "02 Pneumococcal Stoecker 508", "content": "1E conomic A ssessment of R outine PC V 20 for C hildren\nC harles Stoecker\nTulane University\nSchool of Public Health and Tropical Medicine\nACIP\nJune 22,  2023\n\n2Conflicts of Interest\nDr. Stoecker has no conflicts of interest to declare.\n3Acronyms\n PC V :  pneumococcal conjugate vaccine\n PCV 13:  13 valent PCV\n PCV 15:  15 valent PCV\n PCV 20:  20 valent PCV\n PPSV 23:  23 valent pneumococcal polysaccharide vaccine\n V E :  vaccine effectiveness\n V T: vaccine type\n ST: s e r o t yp e\n AOM: acute otitis media\n NBP : n o n -bacteremic  pneumonia\n IPD: invasive p neumococcal disease\n IPT: inp atient\n OPT :  outpatient\n QAL Y : quality adjusted life year\n I C :  immunocompromised\n CMC: chronic medical conditions, b ut not IC\n C PI :  C onsumer price index\n NIS: National Immunization Survey\n ABCs: Active Bacterial Core Surveillance System\n4Policy Question 1\nShould PCV20 be recommended as an option for \npneumococcal conjugate vaccination according to currently \nrecommended dosing and schedules, for U.S. children aged \n<2 years?\nEvaluate the disease and cost impacts of using PCV20 in \nplace of existing conjugate vaccines in six interventions:\nIntervention Comparator Population\nP CV2 0 P CV1 3 Healthy\nPCV 20+PPSV PCV 13+PPSV CMC\nPCV 20+PPSV +PPSV PCV 13+PPSV +PPSV IC\nP CV2 0 P CV1 5 Healthy\nPCV 20+PPSV PCV 15+PPSV CMC\nPCV 20+PPSV +PPSV PCV 15+PPSV +PPSV IC\nC onjugate doses are given in a 3+1 schedule (3 doses at age 0,  1 dose at age 1),\nPPSV  doses are given at age 2 for CMC &  I C and at age 7 for I C\n5Policy Question 2\nShould PCV20 without PPSV23 be recommended as an \noption for pneumococcal vaccination for U.S. children aged \n2–18 years with underlying medical conditions that \nincrease the risk of pneumococcal disease?\nEvaluate the disease and cost impacts of using PCV20 in \nplace of existing schedules that include conjugate and \npolysaccharide in six interventions:\nIntervention Comparator Population\nP CV2 0 PCV 13+PPSV CMC\nP CV2 0 PCV 13+PPSV +PPSV IC\nP CV2 0 PCV 15+PPSV CMC\nP CV2 0 PCV 15+PPSV +PPSV IC\nPCV 20+PPSV P CV2 0 CMC\nPCV 20+PPSV +PPSV P CV2 0 IC\nC onjugate doses are given in a 3+1 schedule (3 doses at age 0,  1 dose at age 1),\nPPSV  doses are given at age 2 for CMC &  I C and at age 7 for I C\n6Methods\nCohort model\nUnited States birth cohort 3,939,295\n•91.1% healthy a\n•8.8% CMC a\n•0.1% IC a\n•Background mortality rates from National Center for Health Statistics \nVital Statistics\nSocietal p ersp ective\n•Medical & nonmedical (work loss) costs\nA ll future outcomes (health &  cost) discounted at 3%\nCosts inflated to 2022$ by CPI or CPI Medical Care\nDisease incidence followed for 15 years after final PCV20 shot\n•Direct & indirect protection followed over this cohort\n•QA L Y  losses from death and permanent disease states aggregated over the lifetime\na Pelton 2014.  T ables 1 &  2.\n7Outcomes\nIPD cases (meningitis & other)\nMeningitis sequelae (deafness & other disability)\nNon-invasive pneumonia (inpatient & outpatient)\nOtitis media & tympanostomy tube placement\nDeaths\nQALYs & life years\nCosts\nCost/QALY\n8Complete Series PCV Vaccine Effectiveness\nVE Reference\nVT IPD (e xce p t  ST3, ST19F) 86 (76,  92) Moore 2016\nST3 IPD 26 (0, 68) Andrews 2014\nST19F IPD 75 (37, 90) Andrews 2014\nVT NBP (except ST3, ST19F) 51.6 (45.6, 55.2) b\nST3 NBP 15.6 (0, 40.8) b\nST19F NBP 45 (22.2, 54) b\nVT AOM (except ST3, ST19F) 54 (41, 64) Eskola  2001\nST3 AOM 16.3 (12.4, 19.3) c\nST19F AOM 47.1 (35.8, 55.8) d\nNote:  T he displayed V E  values apply only after receipt of 4th dose.   V E  during the 1st year (age 0 -1) is 75.7% of these numbers.   \n(A dapted from Whitney et al.   2006)\nb A pplied ratio of V E  for NB P to V E  for I PD for adults from C A PI T A  study to pediatric V E s vs I PD above\nc Ap p lied ratio of p ediatric ST3 IPD to other VT IPD ab ove to Esko la  estimate for V T  A OM  \nd Ap p lied ratio of p ediatric ST19F IPD to other VT IPD ab ove to Esko la  estimate for V T  A OM\n9PPSV Vaccine Effectiveness\nVE Source\nVT IP D 59.7 (47.4,  69.1)Falkenhorst  2017 & \nThorrington  2018\nVT NBP 20 (0, 40) ACIP WG Discussion\nVT AOM 0 ACIP WG Discussion\n10Indirect Effects\nEffects on other children\nA pply to unvaccinated children and children whose vaccination protection is not \n100% (i.e., all children)\nA pply to PC V 20 unique types only\nR emove 7.8% of disease each year\nEffects on adults\nFor childhood cohort model, modeled effects on all U.S. adults (258 million)  \nU sed inputs from our model previously used to analyze PC V 20 effects on adults\nModeled 1 year of impacts on adults for this childhood cohort\n•2nd year of impacts on adults would be influenced by 2nd childhood cohort,  etc.\nU sed output from previously used C DC  Win BUGS  model that shows each childhood \ncohort responsible for 4.12% decline in previous year’ s disease on average\n•W e modified this 4.17% to account for an anticipated 15 years of use to arrive at an average of 3.12% \ndisease reduction per childhood cohort\nI ndirect effects from adults (QA L Y s and cost savings) were then apportioned to \neach risk status of children according to their contribution to total QA L Y s saved.   \n•If vaccinating healthy children was resp onsib le for 50% of total QAL Ys saved among \nchildren,  then 50% of cost and QA L Y  savings from adults were allocated to the healthy \ngroup.\n11Other Vaccine Assumptions\nCoverage\n3-dose PC V  series (completed by 13 months,  applied to 1st year)\n•94.2% (93.6, 94.8)  Hill MMWR 2023\n4-dose PC V  series\n•81.9% (80.9,  82.2) Hill MMWR  2023\n1st d o se  PPSV (CMC & IC)\n•78.1%\n2nd d ose PPSV (IC)\n•64.0%\nWaning\nP C V: Ye a r s  0 -5 get full VE\n•Waning linearly to 0% over next 10 years\nPPSV : Wane linearly to 50% in first 5 years\n•W ane linearly to 30% in next 5\n•W ane to 0% in last 5 years\nAdverse events\nA ll vaccines were assumed to have no adverse events\n12AOM Incidence\nAg e 0 1 2 3 4\nAll cause AOM visits, \n   healthy (p er 1k) a507 \n(358,701 )507 \n(358,701 )319 \n(229,435)319 \n(229,435)319 \n(229,435)\nAll cause AOM visits, \n   CMC/ IC (p e r 1k) b1533 \n(1083,2117)1533 \n(1083,2117)686 \n(491,936)686 \n(491,936)686 \n(491,936)\n% of A OM  with tympanostomy \ntube insertion c12% (6- 15) 12% (6- 15) 8% (4 -15)8% (4 -15)8% (4 -15)\n% pneumococcal A OM  d 14.0% 14.0% 16.0% 16.0% 16.0%\nNote:   No A OM  incidence assumed for ages 5+.a overall numb ers from National Amb ulatory Medical Survey/National Hosp ital Amb ulatory Medical Care Survey+Market  Scan data \n2016+2018,b Market Scan Data 2016 -2018\nc Pichichero  et al.   2013\nd K aur et al.   2022\n13NBP Incidence\nAge 0 1 2 3 4 5 6 7 8 9+\nOPT  NB P ,  healthy (per \n100k) a640 \n(594,686)1291 \n(1192,1386)1512 \n(1368,1658)785 \n(715,859)639 \n(583,693)678 \n(618,733)575 \n(524,622)711 \n(626,800)357 \n(323,391)319 \n(294,345)\nOPT NBP, CMC/ IC (p e r 100k) \nb9249 \n(56388,\n65090)18656 \n(113162,\n131601)14881 \n(74090,\n89811)7728 \n(38714,\n46492)6294 \n(31556,\n37506)5060 \n(21862,\n25905)4296 \n(18546,\n21986)5308 \n(22121,\n28290)2664 \n(11413,\n13815)2384 \n(10384,\n12189)\n% pneumococcal c 6% (1 -10) 6% (1 -10) 6% (1 -10) 6% (1 -10) 6% (1 -10) 6% (1 -10) 6% (1 -10) 6% (1 -10) 6% (1 -10) 6% (1 -10)\nI PT  NB P ,  healthy (per 100k) \nd588 \n(546,630)417 \n(385,448)390 \n(353,427)202 \n(184,221)165 \n(150,179)121 \n(111,131) 103 (94,112)127 \n(112,143) 64 (58,70) 57 (52,61)\nIPT NBP, CMC (p e r 100k) \ne\n1642 \n(1524,1759)1164 \n(1075,1250)1087 \n(984,1193)564 \n(514,617)461 \n(420,499)544 \n(496,588)462 \n(422,500)568 \n(500,639)286 \n(258,313)255 \n(235,275)\nIPT  NB P ,  IC (per 100k) \ne\n3283 \n(3048,3518)2328 \n(2150,2501)2174 \n(1968,2386)1128 \n(1027,1234)922 \n(840,998)1328 \n(1212,1436)1129 \n(1029,1220)1386 \n(1220,1560)697 \n(631,764)623 \n(573,672)\n% IPT NPB fatality d\n1.3% (1.02 -\n1.59)0.53% \n(0.37- 0.70)0.40% \n(0.23- 0.58)0.42% \n(0.21- 0.64)0.61% \n(0.32- 0.91)0.39% \n(0.15- 0.63)0.32% \n(0.06- 0.59)0.78% \n(0.35- 1.20)0.51% \n(0.13- 0.89)1.72% \n(1.42- 2.01)\n% pneumococcal c 12% (2- 20)12% (2- 20)12% (2- 20)12% (2- 20)12% (2- 20)12% (2- 20)12% (2- 20)12% (2- 20)12% (2- 20)12% (2- 20)\na overall mean from Tong et al. 2018, 5th & 9 5th p ercentiles calculated using the ratio of 5th & 9 5th to mean in I PT  NB P for each age; adjusted by (1 -% CMC+IC p o p  * CMC+IC \nratio)/% healthy pop;  C MC +I C  ratio from MarketScan  2016 -2018\nb based on Tong et al. 2018, but scaled by age -sp ecific ratios of CMC+IC to healthy calculated from MarketScan  2016 -2018\nc A dapted from Jain et al. 2015 with expert input.d Overall numbers from 2018 -2019 NIS Data, scaled by (1 -(% IC p o p  * IC ratio  + % CMC p o p  * CMC ratio )) /  % h e alth y p o p , ratio s f o r IC an d  CMC fro m  Pe lto n  e t al. 2014\ne Overall numbers from 2018 -2019 NI S Data, scaled by rate ratios for health: CMC:I C from Pelton et al. 2014\n14IPD Incidence\nAg e 0 1 2 3 4 5 6 7 8 9+\nIPD In cid e n ce , \nhealthy (per 100k) \na14 (11, 16) 10 (7, 12) 5 (3, 6) 5 (3, 6) 3 (2, 4) 5 (3, 6) 3 (1, 4) 2 (1, 3) 1 (0, 2) 1 (1, 1)\nIPD In cid e n ce , CMC (p e r 100k) \na24 (20,29) 18 (13,22) 8 (5,11) 9 (5,11) 6 (4,7) 15 (10,20) 9 (3,13) 7 (3,10) 5 (0,7) 3 (3,3)\nIPD In cid e n ce , IC (per 100k) \na152\n(123,179)112\n(78,134)51\n(34,67)54\n(34,67)34\n(22,45)182 \n(120,241)112 \n(40,160)81\n(40,120)56\n(0,80)40\n(40,40)\n% meningitis a15.87 \n(14.45,17.43)15.87 \n(14.45,17.43)15.87 \n(14.45,17.43)15.87 \n(14.45,17.43)15.87 \n(14.45,17.43)20.05 \n(18,22.33)20.05 \n(18,22.33)20.05 \n(18,22.33)20.05 \n(18,22.33)20.05 \n(18,22.33)\n% meningitis resulting in fatality  \na10.48 \n(7.85,13.99)10.48 \n(7.85,13.99)10.48 \n(7.85,13.99)10.48 \n(7.85,13.99)10.48 \n(7.85,13.99)0.00% 0.00% 0.00% 0.00% 0.00%\n% o t h e r IPD resulting in fatality  \na3.61\n(2.92,4.47)3.61\n(2.92,4.47)3.61 \n(2.92,4.47)3.61 \n(2.92,4.47)3.61 \n(2.92,4.47)3.83 \n(2.93,5.02)3.83 \n(2.93,5.02)3.83 \n(2.93,5.02)3.83 \n(2.93,5.02)3.83 \n(2.93,5.02)\na AB C’ s data 2018- 2019.\nb Olarte  et al.  2015;  E dmond et al.  2010Ag e 0-4 5+\nDisability % b 7 (4,  11) 11 (8, 18)\nDeafness % b 9 (7,  13) 14 (11, 22)Meningitis Sequelae\n15IPD/NBP Serotype Distributions\nAg e 0 1 2 to 5 6+\n% PCV 13 (+6C -3-19F) 3.68% 1.23% 9.76% 10.64%\n% ST3 11.90% 3.68% 10.93% 14.22%\n% ST19F 7.35% 7.37% 5.65% 9.17%\n% PCV 15 only (ST 22F ,  33F) 17.41% 21.01% 14.97% 14.14%\n% PCV20 only 12.86% 19.78% 11.45% 13.52%\n% PPSV23 only 1.84% 1.23% 0.73% 5.83%\n% PCV 13 (+6C -3-19F) 3.06%\n% ST3 3.06%\n% ST19F 3.06%\n% PCV 15 only (ST 22F ,  33F) 8.16%\n% PCV20 only (ST 8, 10A, 11A, \n12F, 15B)23.47%AOM Serotype Distributions\nIPD serotype distributions from AB Cs data 2018 -2019.   Applied to NB P by assumption.\nAOM serotyp e distrib utions from Kaur et al. 2022 modified by exp ert inp ut.\n16Vaccine Prices\nPCV 13 Private $226.43 CDC Price Listb\nPCV13 Pub lic $158.18 CDC Price List\nPCV 15 Private $216.086 CDC Price Listb\nPCV15 Pub lic $162.27 CDC Price List\nPCV20 Private $253.96 a \nPCV20 Public $187.27 a \nPPSV23 Private $117.08 CDC Price Listb\nPPSV23 Public $65.80 CDC Price List\nV accine Admin $30.13 Tsai Prev  Med Reports 2019\nTravel/Caregiver Time $35.96 Maciosek  Am J Prev  Med 2006\na Ratio of PCV20:PCV15 cost in adults sep arately for p ub lic and p rivate from CDC Price list and ap p lied to PCV15 costs in childr e n . \nE stimation procedure discussed with manufacturer.\nb Private list price inflated 7.1% to account for differences between C DC  private list price and average reimbursement (L eidn er e t  a l. \n2021)\n17Disease Cost ($)\nMedical cost aNon-medical \ncost b, c\nDisability $258,084 ($206,467,  $309,701) $1,413,847 \nDeafness $48,354 ($38,683,  $58,025) $583,399 \nAOM $83 ($67,  $100) $253 \nTym p  tube $3,610 ($2,888,  $4,332) $253 \nIPD $19,196 ($15,357,  $23,035) $624 \nIPD-mening $25,691 ($20,553,  $30,829) $3,273 \nIPT NBP $10,965 ($8,772,  $13,158) $624 \nOPT NBP $351 ($281,  $421) $467 \na Medical costs are from MarketScan  2004- 2006 data inflated to 2022$ using Medical component of CPI.   R anges +/ - 20%.  \nb Disability &  deafness:  MMWR  53(03);57- 59 and Errata. E.g.: assistive devices, home modifications, sp ecial education costs, \np roductivity losses, etc.\nc Other conditions:  R ay et al.  2006 PIDJ\n18QALY Decrements\nAOM 0.0016 (0,  0.0155)\nTym p  tube 0.0016 (0,  0.0155)\nOPT NBP 0.0004 (0.0001,  0.0329)\nIPT disease (not mening ) 0.0105 (0.0001,  0.0155)\nIPD mening  no sequelae 0.0165 (0.0001,  0.0166)\nDeafness 0.2137 (0.07,  0.72)\nDisability 0.2456 (0.16,  0.49)\nQA L Y  decrement are low,  median,  and high estimates from the survey by T ang et al.  2021.  T he upper bound of A OM  is capped at t he \nupper bound of inpatient disease.  T ympanostomy tube placement which follows Delgleize  et al. 2016 in setting equal to AOM.\nQA L Y  decrements are scaled by background QA L Y  values which range from 0.94 for age 0 to 0.92 for age 15 (E rickson et al.  Stat istical \nNotes 1995)\n19Indirect Effects from Adult Program\nBa s e\n(indirect rate = \n3.17%)10% less effective \n(indirect rate = \n2.853%)Same effect as on \nkids\n(indirect rate = 7.8%)\nHealth Outcomes\nIPD ca se s -182 -164 -447\nI PT  pneumonia cases -3,210 -2,889 -7,899\nOPT  pneumonia Cases -7,335 -6,601 -18,048\nDeaths due to I PD -24 -21 -59\nDeaths due to pneumonia -127 -115 -314\nQ A LYs 1,262 1,136 3,105\nLife-years 1,849 1,664 4,549\nCosts (million $)\nT otal cost -$80 -$72 -$197\nMedical costs -$80 -$72 -$197\nV accine costs $0 $0 $0\n20Policy Questions\n1.PCV20 in place of existing conjugate vaccines among \nall risk groups.\n2.PCV20 in place of existing schedules that include \nconjugate and polysaccharide among CMC & IC \npopulations\n21Direct Swap PCV20 for PCV13\nPCV 20 vs PCV 13PCV 20+PPSV  vs \nPCV 13+PPSVPCV 20+PPSV +PPSV  vs \nPCV 13+PPSV +PPSV  \nHealthy CMC IC\nIPD meningitis cases -55 -8 -1\nIPD n o n -meningitis cases -276 -40 -3\nDeafness -4 -1 0\nDisab ility -6 -1 0\nI PT  pneumonia cases -1,106 -277 -7\nOPT  pneumonia cases -1,798 -1,552 -18\nAOM ca s e s -145,371 -36,645 -444\nTy m p  tubes -14,647 -3,815 -46\nDeaths due to I PD -14 -2 0\nDeaths due to pneumonia -8 -2 0\nChildhood QAL Ys 917 190 7\nAdult QAL Ys (indirect) 1,039 215 8\nLife-years 685 128 7\nCosts (million $)\nT otal cost $153 -$17 -$0.92\nMedical costs -$108 -$27 -$0.56\nNon-medical costs -$52 -$13 -$0.27\nAdult costs (indirect) -$66 -$14 -$0.53\nV accine costs $379 $37 $0.44\nCost ratios ($)\nC o s t / Q A LY 78,115 Cost-saving Cost-saving\nCost/life -year 223,192 Cost-saving Cost-savingPolicy Question 1\n22Direct Swap PCV20 for PCV15\nPCV 20 vs PCV 15\nHealthyPCV 20+PPSV  vs \nPCV 15+PPSV\nCMCPCV 20+PPSV +PPSV  vs \nPCV 15+PPSV +PPSV\nIC\nIPD menigitis  cases -25 -4 0\nIPD n o n -meningitis cases -125 -18 -2\nDeafness -2 0 0\nDisab ility -3 0 0\nI PT  pneumonia cases -500 -126 -3\nOPT  pneumonia cases -824 -716 -8\nAOM ca s e s -107,856 -27,188 -329\nTy m p  tubes -10,867 -2,830 -34\nDeaths due to I PD -7 -1 0\nDeaths due to pneumonia -4 -1 0\nChildhood QAL Ys 488 104 4\nAdult QAL Ys (indirect) 1,033 221 8\nLife-years 308 58 3\nCosts (million $)\nT otal cost $234 -$1 -$0.48\nMedical costs -$68 -$17 -$0.32\nNon-medical costs -$35 -$9 -$0.16\nAdult costs (indirect) -$65 -$14 -$0.48\nV accine costs $402 $39 $0.47\nCost ratios ($)\nC o s t / Q A LY 153,715 Cost-saving Cost-saving\nCost/life -year 757,901 Cost-saving Cost-savingPolicy Question 1\n23Direct Swap PCV20 for PCV15\nSensitivity Analysis: PCV20 VE 10% Lower\nPCV 20 vs PCV 15 PCV 20+PPSV  vs \nPCV 15+PPSV  PCV 20+PPSV +PPSV  vs \nPCV 15+PPSV +PPSV\nHealthy CMC IC\nIPD meningitis cases -16 -2 0\nIPD n o n -meningitis cases -82 -10 -1\nDeafness -1 0 0\nDisab ility -2 0 0\nIPT pneumonia cases -392 -95 -2\nOPT pneumonia cases -651 -542 -6\nAOM cases -85,628 -21,597 -262\nTy m p  tubes -8,633 -2,250 -27\nDeaths due to I PD -4 -1 0\nDeaths due to pneumonia -3 -1 0\nChildhood QAL Ys 360 76 2\nAdult QAL Ys (indirect) 933 197 6\nLife-years 216 39 2\nCosts (million $)\nT otal cost $263 $6 -$0.22\nMedical costs -$53 -$13 -$0.22\nNon-medical costs -$27 -$7 -$0.11\nAdult costs (indirect) -$59 -$12 -$0.36\nV accine costs $402 $39 $0.47\nCost ratios ($)\nC o s t / Q A LY 203,365 23,832 Cost-saving\nCost/life -year 1,216,977 168,181 Cost-savingPolicy Question 1\n24Direct Swap PCV20 for PCV15\nSensitivity Analysis: Adult Indirect Effects 7.8%\nPCV 20 vs PCV 15 PCV 20+PPSV  vs \nPCV 15+PPSV  PCV 20+PPSV +PPSV  vs \nPCV 15+PPSV +PPSV  \nHealthy CMC IC\nIPD meningitis cases -25 -4 0\nIPD n o n -meningitis cases -125 -18 -2\nDeafness -2 0 0\nDisab ility -3 0 0\nIPT pneumonia cases -500 -126 -3\nOPT pneumonia cases -824 -716 -8\nAOM cases -107,856 -27,188 -329\nTy m p  tubes -10,867 -2,830 -34\nDeaths due to I PD -7 -1 0\nDeaths due to pneumonia -4 -1 0\nChildhood QAL Ys 488 104 4\nAdult QAL Ys (indirect) 2,542 545 19\nLife-years 308 58 3\nCosts (million $)\nT otal cost $138 -$21 -$1.18\nMedical costs -$68 -$17 -$0.32\nNon-medical costs -$35 -$9 -$0.16\nAdult costs (indirect) -$161 -$35 -$1.17\nV accine costs $402 $39 $0.47\nCost ratios ($)\nC o s t / Q A LY 45,551 Cost-saving Cost-saving\nCost/life -year 447,389 Cost-saving Cost-savingPolicy Question 1\n25Direct Swap PCV20 for PCV15, Healthy\nMultivariate Sensitivity, 90% Confidence Interval\nPCV 20 vs PCV 15 5th 95th\nHealthy Healthy Healthy\nIPD meningitis cases -25 -28 -21\nIPD n o n -meningitis cases -125 -135 -104\nDeafness -2 -3 -1\nDisab ility -3 -4 -2\nIPT pneumonia cases -500 -829 -82\nOPT pneumonia cases -824 -1,363 -136\nAOM cases -107,856 -130,202 -87,612\nTy m p  tubes -10,867 -14,286 -7,866\nDeaths due to I PD -7 -8 -5\nDeaths due to pneumonia -4 -6 -1\nChildhood QAL Ys 488 362 1,263\nAdult QAL Ys (indirect) 1,033 402 2,541\nLife-years 308 206 388\nCosts (million $)\nT otal cost $234 $135 $279\nMedical costs -$68 -$85 -$49\nNon-medical costs -$35 -$42 -$30\nAdult costs (indirect) -$65 -$162 -$24\nV accine costs $402 $401 $404\nCost ratios ($)\nC o s t / Q A LY 153,715 51,105 210,518\nCost/life -year 757,901 409,958 1,144,176Policy Question 1\n26Direct Swap PCV20 for PCV15, Healthy\nOne-way Sensitivity\nInfluential Inputs on Cost/QALY\nAll inp uts were included in multivariate sensitivity analysis.  The top  5 according to size of change in cost p er QAL Y are ch arted \nhere.   E nds of bars represent the cost/QA L Y  when the particular input is set to the min/max (or 5th & 9 5th) of the input \ndistrib ution. $-  $50,000  $100,000  $150,000  $200,000  $250,000  $300,000  $350,000  $400,000VE PCV vs AoM !ST3 !ST19IPT NBP due to pneumococcusAoM QALY DecrementIndirect Adult CostsIndirect Adult QALYsPolicy Question 1\n27PCV20 without PPSV23, PCV13 Context\nPCV 20 vs PCV 13+PPSV PCV 20 vs PCV 13+PPSV +PPSV  \nCMC IC\nIPD meningitis cases -7 -1\nIPD n o n -meningitis cases -35 -3\nDeafness -1 0\nDisab ility -1 0\nI PT  pneumonia cases -267 -6\nOPT  pneumonia cases -1,497 -17\nAOM ca s e s -36,645 -444\nTy m p  tubes -3,815 -46\nDeaths due to I PD -2 0\nDeaths due to pneumonia -2 0\nChildhood QAL Ys 180 6\nAdult QAL Ys (indirect) 204 7\nLife-years 118 6\nCosts (million $)\nT otal cost -$55 -$1.57\nMedical costs -$27 -$0.51\nNon-medical costs -$12 -$0.24\nAdult costs (indirect) -$13 -$0.45\nV accine costs -$3 -$0.38\nCost ratios ($)\nC o s t / Q A LY Cost-saving Cost-saving\nCost/life -year Cost-saving Cost-savingPolicy Question 2\n28PCV20 without PPSV23, PCV15 Context\nPCV 20 vs \nPCV 15+PPS\nCMC\nVPCV 20 vs \nPCV 15+PPSV +PPSV  \nICPCV 20 vs PCV 15+PPSV , \nHalf PPSV  Coverage\nCMCPCV 20 vs \nPCV 15+PPSV +PPSV , \nHalf PPSV  Coverage\nIC\nIPD meningitis cases -3 0 -4 0\nIPD n o n -meningitis cases -13 -1 -21 -2\nDeafness 0 0 0 0\nDisab ility 0 0 0 0\nIPT pneumonia cases -116 -2 -138 -3\nOPT  pneumonia Cases -661 -7 -786 -9\nAOM cases -27,188 -329 -27,188 -329\nTy m p  tubes -2,830 -34 -2,830 -34\nDeaths due to I PD -1 0 -1 0\nDeaths due to pneumonia -1 0 -1 0\nChildhood QAL Ys 95 3 111 4\nAdult QAL Ys (indirect) 108 3 125 5\nLife-years 48 2 64 4\nCosts (million $)\nT otal cost -$33 -$0.91 $4 -$0.66\nMedical costs -$17 -$0.26 -$18 -$0.34\nNon-medical costs -$8 -$0.12 -$9 -$0.18\nAdult costs (indirect) -$7 -$0.18 -$8 -$0.29\nV accine costs -$1 -$0.35 $39 $0.15\nCost ratios ($)\nC o s t / Q A LY Cost-saving Cost-saving 18,722 Cost-saving\nCost/life -year Cost-saving Cost-saving 68,612 Cost-savingPolicy Question 2\n29Adding PPSV23 to a PCV20 Primary Series\nPCV 20+PPSV  vs PCV 20PCV 20+PPSV +PPSV  vs \nP CV2 0\nCMC IC\nIPD meningitis cases -1 0\nIPD n o n -meningitis cases -5 -1\nDeafness 0 0\nDisab ility 0 0\nI PT  pneumonia cases -10 -1\nOPT  pneumonia cases -55 -1\nAOM ca s e s 0 0\nTy m p  tubes 0 0\nDeaths due to I PD 0 0\nDeaths due to pneumonia 0 0\nQ A LYs 9 1\nLife-years 10 1\nCosts (million $)\nT otal cost 39 $0.73\nMedical costs -1 -$0.06\nNon-medical costs 0 -$0.04\nV accine costs 40 $0.82\nCost ratios ($)\nS a v i n g s / Q A LY 4,086,881 690,388\nSavings/life -year 3,923,758 658,925Policy Question 2\n30Limitations\nUncertainty around indirect effects on adults\nUncertainty around QALY decrements\nAOM\nPCV20 VE based on immunogenicity trials\nSa m e  VE fo r  a ll P CV valencies\nST3 VE limited data\n31Conclusion\nPolicy Question 1\nReplacing PCV13 with PCV20 costs: \n$57k/QAL Y  (aggregate)\n•$78k/QAL Y  (healthy)\n•Co st -savin g  (CMC)\n•Co st -Saving (IC)\nReplacing PCV15 with PCV20 costs: \n$125k/QAL Y  (aggregate)\n•$154k/QAL Y  (healthy)\n•Co st -savin g  (CMC)\n•Co st -sa vin g  (IC)\n32Replacing PCV13+PPSV23 (or PCV15+PPSV23) with PCV20 \nby itself in CMC/IC is cost saving\nAdding PPSV23 to PCV20 for CMC/IC costs: \n$3.9 million/QAL Y  (aggregate)\n•$4.1 million/QAL Y (CMC)\n•$0.7 million/QAL Y (IC)Conclusion\nPolicy Question 2\n33Thank you!\nPlease send comments to:\ncfstoecker@tulane.edu\nContributors:\nMiwako Kobayashi\nDipreye  Ayabina\nNamrata Prasad\nAndrew Leidner\nH\nSREB – Ec o n  Te a mNational Center for Immunization & Resp iratory Diseases", "summary": "1E conomic A ssessment of R outine PC V 20 for C hildren C harles Stoecker Tulane University School of Public Health and Tropical Medicine ACIP June 22,  2023  2Conflicts of Interest Dr. Stoecker has no conflicts of interest to declare. 3Acronyms  PC V :  pneumococcal conjugate vaccine  PCV 13:  13 valent PCV  PCV 15:  15 valent PCV  PCV 20:  20 valent PCV  PPSV 23:  23 valent pneumococcal polysaccharide vaccine  V E :  vaccine effectiveness  V T: vaccine type  ST: s e r o t yp e …", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/02-Pneumococcal-Stoecker-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 33}
{"title": "03 Pneumococcal Ayabina 508", "content": "Summary of three economic analyses of the use of \n20-valent pneumococcal conjugate vaccine (PCV20) \nin children in the United States\nDiepreye V. Ayabina\nDivision of Bacterial Diseases\nCDC/NCIRDAdvisory Committee on Immunization Practices \nJune 22, 2023\nAcknowledgements\n•This presentation summarizes work conducted by three modeling teams\n•Tulane -CDC team\n•Charles Stoecker (Tulane University), Miwako Kobayashi (CDC), Andrew Leidner (CDC), Diepreye\nAyabina\n•Pfizer team\n•Mark Rozenbaum , Liping Huang, Alejandro Cane, Erica Chilson, Adriano Arguedas, Maria J. Tort, \nRaymond Farkouh , Vincenza Snow\n•Merck team\n•Min Huang, Jessica Weaver, Elamin Elbasha\nViews and opinions expressed in this presentation are the authors and do not necessarily represent the \nviews and opinions of the Centers for Disease Control and Prevention.2\nConflicts of interest statement\n•Diepreye Ayabina: None.\n•Tulane -CDC team: None.\n•Pfizer team:\n•Pfizer manufactures the PCV13 and PCV20 vaccines.\n•Merck team:\n•Merck manufactures the PCV15 and PPSV23 vaccines\n3\nTerminology\nAbbreviation Full term/Meaning\nAOM Acute otitis media\nCMC Chronic medical conditions but not immunocompromised1\nIC Immunocompromising conditions2\nICER Incremental cost -effectiveness ratio\nIPD Invasive pneumococcal disease\nPCV13 13-valent pneumococcal conjugate vaccine\nPCV15 15-valent pneumococcal conjugate vaccine\nPCV20 20-valent pneumococcal conjugate vaccine\nPPSV23 Pneumococcal polysaccharide vaccine (23 serotypes)\nQALYs Quality -adjusted life -years\n1Includes chronic heart, lung, and liver diseases, diabetes.\n2Includes chronic renal failure, nephrotic syndrome, congenital immunodeficiency, congenital or acquired asplenia, or splenic dysfunction, diseases associated with treatment of immunosuppressive drugs \nor radiation therapy such as Hodgkin disease, leukemia, lymphoma, malignant neoplasm and solid organ transplant, HIV and sick le cell disease. 4\nOutline\n•Introduction\n•Policy question #1: (Routine use of PCV20)\n•Model description\n•Estimated health outcomes and cost results\n•Overview of cost -effectiveness results \n•Model assumptions driving differences + sensitivity analysis\n•Policy question #2: (Use of PCV20 in with underlying medical conditions that increase the risk of \npneumococcal disease)\n•Estimated health outcomes and cost results\n•Overview of cost -effectiveness results \n•Model assumptions driving differences + sensitivity analysis\n•Summary\n5\nIntroduction\n•This presentation describes three cost -effectiveness models that have been used to examine the costs and \nbenefits of including PCV20 as an option in the childhood immunization schedule developed. \n•Tulane -CDC, Pfizer, and Merck\n•Results of this presentation focus on routine use of PCV20 among <2 -year -olds, and among 2 -18-year -olds \nwith underlying conditions. \n•Assessments of a supplemental PCV20 dose in children who completed the PCV series with PCV13 or PCV15 are not included\n•All three reports went through the CDC economic review following the ACIP Guidance for Health Economics \nStudies\n•Completion of the economic review does not confer any explicit or implied approval of the model\n6\nPolicy question 1\nRoutine use of PCV20 in children\nPolicy question #1\nShould PCV 20berecommended as an option for pneumococcal\nconjugate vaccination according tocurrently recommended dosing and\nschedules, for children aged <2 years inthe United States?\n𝐶𝑜𝑠𝑡𝑠𝐼𝑛𝑡𝑒𝑟𝑣𝑒𝑛𝑡𝑖𝑜𝑛 −𝐶𝑜𝑠𝑡𝑠 𝐶𝑜𝑚𝑝𝑎𝑟𝑎𝑡𝑜𝑟= 𝑰𝒏𝒄𝒓𝒆𝒎𝒆𝒏𝒕𝒂𝒍𝒄𝒐𝒔𝒕 −𝒆𝒇𝒇𝒆𝒄𝒕𝒊𝒗𝒆𝒏𝒆𝒔𝒔𝒓𝒂𝒕𝒊𝒐(𝑰𝑪𝑬𝑹)𝑂𝑢𝑡𝑐𝑜𝑚𝑒𝑠 𝐼𝑛𝑡𝑒𝑟𝑣𝑒𝑛𝑡𝑖𝑜𝑛 −𝑂𝑢𝑡𝑐𝑜𝑚𝑒𝑠 𝐶𝑜𝑚𝑝𝑎𝑟𝑎𝑡𝑜𝑟Intervention (dosing) Comparator (dosing)\nPCV20 (3+1) PCV13 (3+1) /PCV15 (3+1)\n8\nDescription of models\nPolicy question #1\nModel characteristics Tulane -CDC Merck Pfizer\nCohort type Single birth cohort Single birth cohort Multi -cohort\nAnalytic model time frame 17 years 100 years 10 years\nInclude indirect effects Yes Yes ( only to IPD incidence) Yes\nBase case perspective Societal Societal Societal\nCurrency year 2022 $ US 2022 $ US 2022 $ US\naVaccine price PCV13: $184\nPCV15: $183\nPCV20: $213PCV13: $192\nPCV15: $189\nPCV20: $213PCV13: $182\nPCV15: $184\nPCV20: $204\nOther vaccine costs per dose Admin: $30; travel: $36 Admin: $19 Admin: $18\naAll three models used blended vaccine prices (vaccine price was weighted average of private and public market prices, weights wer e private and public market shares, which \nvaried across the models).\n9\nHealth outcomes and cost resultsa\nPCV20 vs PCV15, base case\nPCV20 vs PCV15\nOutcomes and cost Tulane -CDC Merck++Pfizer\nHealth outcomesIPD cases -360 -400 -30,000*\nPneumonia cases -13,000 -2,300 -1,400,000*\nAOM cases -150,000 -201,000 -3,000,000*\nDeaths -160 -28 -9,700*\nQALYs 1,900 1,400 280,000\nCosts ($ millions)Cost of disease + sequelae -210 -180 -12,000\nVaccine costs 440 330 2,100\nTotal cost 230 150 -10,000\n10aThese are discounted values (rounded up to 2 significant figures) for the complete horizon for the base case of each model \n*Outcomes not reported as discounted values.\nAll other values were discounted at 3%.\nNegative values indicate averted cases/deaths or reduced costs of PCV20, as compared to PCV15.\n++Pfizer base case results involve vaccination of 10 cohorts of children, results from single cohort shown in supplemental slid e.\nPCV20 vs PCV15\nOutcomes and cost Tulane -CDC Merck++Pfizer\nHealth outcomesIPD cases -360 -400 -30,000*\nPneumonia cases -13,000 -2,300 -1,400,000*\nAOM cases -150,000 -201,000 -3,000,000*\nDeaths -160 -28 -9,700*\nQALYs 1,900 1,400 280,000\nCosts ($ millions)Cost of disease + sequelae -210 -180 -12,000\nVaccine costs 440 330 2,100\nTotal cost 230 150 -10,000\n11aThese are discounted values (rounded up to 2 significant figures) for the complete horizon for the base case of each model \n*Outcomes not reported as discounted values.\nAll other values were discounted at 3%.\nNegative values indicate averted cases/deaths or reduced costs of PCV20, as compared to PCV15\n++Pfizer base case results involve vaccination of 10 cohorts of children, results from single cohort shown in supplemental slid e.Health outcomes and cost resultsa\nPCV20 vs PCV15, base case\nPCV20 vs PCV15\nOutcomes and cost Tulane -CDC Merck++Pfizer\nHealth outcomesIPD cases -360 -400 -30,000*\nPneumonia cases -13,000 -2,300 -1,400,000*\nAOM cases -150,000 -201,000 -3,000,000*\nDeaths -160 -28 -9,700*\nQALYs 1,900 1,400 280,000\nCosts ($ millions)Cost of disease + sequelae -210 -180 -12,000\nVaccine costs 440 330 2,100\nTotal cost 230 150 -10,000\n12aThese are discounted values (rounded up to 2 significant figures) for the complete horizon for the base case of each model \n*Outcomes not reported as discounted values.\nAll other values were discounted at 3%.\nNegative values indicate averted cases/deaths or reduced costs of PCV20, as compared to PCV15.\n++Pfizer base case results involve vaccination of 10 cohorts of children, results from single cohort shown in supplemental slid e.Health outcomes and cost results\nPCV20 vs PCV15, base casea\nPCV20 vs PCV15\nOutcomes and cost Tulane -CDC Merck++Pfizer\nHealth outcomesIPD cases -360 -400 -30,000*\nPneumonia cases -13,000 -2,300 -1,400,000*\nAOM cases -150,000 -201,000 -3,000,000*\nDeaths -160 -28 -9,700*\nQALYs 1,900 1,400 280,000\nCosts ($ millions)Cost of disease + sequelae -210 -180 -12,000\nVaccine costs 440 330 2,100\nTotal cost 230 150 -10,000\n13aThese are discounted values (rounded up to 2 significant figures) for the complete horizon for the base case of each model \n*Outcomes not reported as discounted values.\nAll other values were discounted at 3%.\nNegative values indicate averted cases/deaths or reduced costs of PCV20, as compared to PCV15.\n++Pfizer base case results involve vaccination of 10 cohorts of children, results from single cohort shown in supplemental slid e.Health outcomes and cost resultsa\nPCV20 vs PCV15, base case\nPCV20 vs PCV15\nOutcomes and cost Tulane -CDC Merck++Pfizer\nHealth outcomesIPD cases -360 -400 -30,000*\nPneumonia cases -13,000 -2,300 -1,400,000*\nAOM cases -150,000 -201,000 -3,000,000*\nDeaths -160 -28 -9,700*\nQALYs 1,900 1,400 280,000\nCosts ($ millions)Cost of disease + sequelae -210 -180 -12,000\nVaccine costs 440 330 2,100\nTotal cost 230 150 -10,000\n14aThese are discounted values (rounded up to 2 significant figures) for the complete horizon for the base case of each model \n*Outcomes not reported as discounted values.\nAll other values were discounted at 3%.\nNegative values indicate averted cases/deaths or reduced costs of PCV20, as compared to PCV15\n++Pfizer base case results involve vaccination of 10 cohorts of children, results from single cohort shown in supplemental slid e.Health outcomes and cost resultsa\nPCV20 vs PCV15, base case\nModel assumptions\n*Indirect effects of pediatric PCV20 vaccination on adult pneumonia incidence\nModelDisease \noutcomes \nimpacted by \nindirect effectsDetails on the indirect effects methodologyAdjust for \nPCV20 use \namong 65+Data years \nfor indirect \neffect on \npneumoniaApproximate \n% of PCV20 \nonly type \npneumoniaApproximate \nreduction in \nPCV20 -only \npneumonia\nper cohort\nMerck •IPD•Assume 8% reduction per year, with a max of \n33% achieved in year 4 and maintained until the \nend of the cohortNo NA (IPD considered only)\n•Higher indirect effects as a result of PCV20 use would lead to PCV20 being more cost -effective when compared to other PCV vaccin es.\n15\nModel assumptions\n*Indirect effects of pediatric PCV20 vaccination on adult pneumonia incidence\nModelDisease \noutcomes \nimpacted by \nindirect effectsDetails on the indirect effects methodologyAdjust for \nPCV20 use \namong 65+Data years \nfor indirect \neffect on \npneumoniaApproximate \n% of PCV20 \nonly type \npneumoniaApproximate \nreduction in \nPCV20 -only \npneumonia\nper cohort\nMerck •IPD•Assume 8% reduction per year, with a max of \n33% achieved in year 4 and maintained until the \nend of the cohortNo NA (IPD considered only)\nTulane -\nCDC•IPD\n•Pneumonia\n•AOM•Based on regression model estimates \n•Estimated impact per vaccinated cohort\n•Indirect effect benefit attributed to birth cohort \nof children who receive PCV20Yes 2013 -2014a 0.6 to 2.4% 3.2%\nPfizer•IPD\n•Pneumonia\n•AOM•Based on observed reduction in all -cause \npneumonia Percentage of PCV20 type disease \nGradual increase in indirect effect over 10 yearsYes2008/2009 to \n2018aGreater than \n1 to 7%0.5 to 3.4%b\n*Higher indirect effects as a result of PCV20 use would lead to PCV20 being more cost effective when compared to other PCV vac cines. The Tulane -CDC  and Pfizer models both accounted for the direct protection in all \nadults.\naThe Tulane -CDC model estimated a monthly reduction in disease due to indirect effects, using data from 2013 and the first half of 2 014 (Pilishvili 2018a; Pilishvili et al. 2018b). The Pfizer model used a total reduction in \ndisease from 2008/2009 to 2018 (Tong et al. 2018, Table 3).\nb.These are approximations based on calculations by the presenting author, based on each cohort in the Pfizer model contributing to i ndirect effects for 5 years. 16\nModel assumptions\n*Indirect effects of pediatric PCV20 vaccination on adult pneumonia incidence\nModelDisease \noutcomes \nimpacted by \nindirect effectsDetails on the indirect effects methodologyAdjust for \nPCV20 use \namong 65+Data years \nfor indirect \neffect on \npneumoniaApproximate \n% of PCV20 \nonly type \npneumoniaApproximate \nreduction in \nPCV20 -only \npneumonia\nper cohort\nMerck •IPD•Assume 8% reduction per year, with a max of \n33% achieved in year 4 and maintained until the \nend of the cohortNo NA (IPD considered only)\nTulane -\nCDC•IPD\n•Pneumonia\n•AOM•Based on regression model estimates \n•Estimated impact per vaccinated cohort\n•Indirect effect benefit attributed to birth cohort \nof children who receive PCV20Yes 2013 -2014a 0.6 to 2.4% 3.2%\nPfizer•IPD\n•Pneumonia\n•AOM•Based on observed reduction in all -cause \npneumonia Percentage of PCV20 type disease \nGradual increase in indirect effect over 10 yearsYes2008/2009 to \n2018aGreater than \n1 to 7%0.5 to 3.4%b\n*Higher indirect effects as a result of PCV20 use would lead to PCV20 being more cost effective when compared to other PCV vac cines. The Tulane -CDC  and Pfizer models both accounted for the direct protection in all \nadults.\naThe Tulane -CDC model estimated a monthly reduction in disease due to indirect effects, using data from 2013 and the first half o f 2014 (Pilishvili 2018a; Pilishvili et al. 2018b). The Pfizer model used a total reduction in \ndisease from 2008/2009 to 2018 (Tong et al. 2018, Table 3).\nb.These are approximations based on calculations by the presenting author, based on each cohort in the Pfizer model contributing to i ndirect effects for 5 years. 17\nCost effectiveness results: base case\nPCV20 vs PCV13\naCost -saving means lower costs and improved health outcomes in the intervention, as compared to the comparator.Intervention Comparator Model Cost per QALY gained\nPCV20 PCV13 Tulane -CDC 57,000\nMerckaCost -saving\nPfizeraCost -saving\nPCV20 PCV15Tulane -CDC 125,000\nMerck 105,003\nPfizeraCost -saving\n18\nCost effectiveness results: base case\nPCV20 vs PCV15\naCost -saving means lower costs and improved health outcomes in the intervention, as compared to the comparator.Intervention Comparator Model Cost per QALY gained\nPCV20 PCV13 Tulane -CDC 57,000\nMerckaCost -saving\nPfizeraCost -saving\nPCV20 PCV15Tulane -CDC 125,000\nMerck 105,003\nPfizeraCost -saving\n19\nSensitivity analysis (Policy question #1)\nCost -effectiveness of routine vaccination with PCV20 for children\nIntervention Comparison ModelCost per QALY gained\nBase case Rangeb\nPCV20 PCV13 Tulane -CDC 57,000 NA\nMerck Cost -saving NA\nPfizer Cost -saving All cost -saving\nPCV20 PCV15 Tulane -CDC 125,000 [31,000 210,000 ]\nMerck 105,000 [8,000              dominateda]\nPfizer Cost -saving [Cost -saving     60,000 ]\naIn one scenario in the Merck model, PCV15 was cost -saving relative to PCV20 (or PCV20 was dominated by PCV15), this scenario as sumed re -emergence of IPD associated with certain \nserotypes that PCV20 missed the trial primary endpoint.\nb The ranges presented are obtained from the scenario analyses and probabilistic sensitivity analysis.\nSensitivity analysis (Policy question #1)\nCost -effectiveness of routine vaccination with PCV20 for children\nIntervention Comparison ModelCost per QALY gained\nBase case Rangeb\nPCV20 PCV13 Tulane -CDC 57,000 NA\nMerck Cost -saving NA\nPfizer Cost -saving All cost -saving\nPCV20 PCV15 Tulane -CDC 125,000 [31,000 210,000 ]\nMerck 105,000 [8,000              dominateda]\nPfizer Cost -saving [Cost -saving     60,000 ]\naIn one scenario in the Merck model, PCV15 was cost -saving relative to PCV20 (or PCV20 was dominated by PCV15), this scenario as sumed re -emergence of IPD associated with certain \nserotypes that PCV20 missed the trial primary endpoint.\nb The ranges presented are obtained from the scenario analyses and probabilistic sensitivity analysis.\nPolicy question 2\nUse of PCV20 in children with underlying medical conditions that increase the risk of pneumococcal disease\nPolicy question #2\nShould PCV20without PPSV23 berecommended as an option for pneumococcal vaccination\naccording tocurrently recommended dosing and schedules, for U.S. children 2 –18years with\nunderlying medical conditions that increase the risk ofpneumococcal disease (CMC/IC)?\n•2.1. What isthe cost effectiveness ofPCV20 alone vsPCV13/ 15+PPSV 23series among CMC/IC?\n•2.2. What isthe cost effectiveness ofadding PPSV 23toa PCV 20series among CMC/IC?\n𝐶𝑜𝑠𝑡𝑠𝐼𝑛𝑡𝑒𝑟𝑣𝑒𝑛𝑡𝑖𝑜𝑛 −𝐶𝑜𝑠𝑡𝑠 𝐶𝑜𝑚𝑝𝑎𝑟𝑎𝑡𝑜𝑟= 𝐼𝑛𝑐𝑟𝑒𝑚𝑒𝑛𝑡𝑎𝑙 𝑐𝑜𝑠𝑡 𝑒𝑓𝑓𝑒𝑐𝑡𝑖𝑣𝑒𝑛𝑒𝑠𝑠 𝑟𝑎𝑡𝑖𝑜(𝐼𝐶𝐸𝑅)𝑂𝑢𝑡𝑐𝑜𝑚𝑒𝑠 𝐼𝑛𝑡𝑒𝑟𝑣𝑒𝑛𝑡𝑖𝑜𝑛 −𝑂𝑢𝑡𝑐𝑜𝑚𝑒𝑠 𝐶𝑜𝑚𝑝𝑎𝑟𝑎𝑡𝑜𝑟Comparator (dosing) Intervention (dosing) Population\nPCV13/15(3+1) + PPSV23 (1) PCV20 (3+1) CMC\nPCV13/15(3+1) + PPSV23 (1+1) PCV20 (3+1) IC\nPCV20(3+1) + PPSV23 (1) PCV20 (3+1) CMC\nPCV20(3+1) + PPSV23 (1+1) PCV20 (3+1) IC\n23\nPolicy question 2.1\nPCV20 alone vs PCV13/15+PPSV23 series among CMC/IC\nHealth outcomes and costs\nPCV20 alone vs PCV15+PPSV23 in CMC, base case\nOutcomes and costPCV20 vs PCV15 + PPSV23\nTulane -CDC Merck Pfizera\nHealth \noutcomesIPD cases -26 -15 -5*\nPneumonia cases -780 -260 -1,100*\nAOM cases -30,000 -28,000 -4,900*\nDeaths -2 -1 -5*\nQALYs 200 140 120\nCosts\n($ millions)Vaccine costs -1 7 5\nCost of disease + sequelae -32 -23 -18\nTotal cost -33 -16 -12\naThese are discounted values (rounded up to 2 significant figures) for the complete horizon for the base case of each model \n*Outcomes not reported as discounted values.\nNegative values indicate averted cases/deaths or reduced costs of PCV20, as compared to PCV15+PPSV23.\na.The Pfizer model does not directly assess policy question 2 but compares the receipt of PCV20 with and without PPSV23 to the receipt of PPSV23 on six -year -\nold children with a history of PCV13 vaccination. \nHealth outcomes and costs\nPCV20 alone vs PCV15+PPSV23 in CMC, base case\nOutcomes and costPCV20 vs PCV15 + PPSV23\nTulane -CDC Merck Pfizera\nHealth \noutcomesIPD cases -26 -15 -5*\nPneumonia cases -780 -260 -1,100*\nAOM cases -30,000 -28,000 -4,900*\nDeaths -2 -1 -5*\nQALYs 200 140 120\nCosts\n($ millions)Vaccine costs -1 7 5\nCost of disease + sequelae -32 -23 -18\nTotal cost -33 -16 -12\naThese are discounted values (rounded up to 2 significant figures) for the complete horizon for the base case of each model \n*Outcomes not reported as discounted values.\nNegative values indicate averted cases/deaths or reduced costs of PCV20, as compared to PCV15+PPSV23.\na.The Pfizer model does not directly assess policy question 2 but compares the receipt of PCV20 with and without PPSV23 to the receipt of PPSV23 on six -year -old \nchildren with a history of PCV13 vaccination. \nHealth outcomes and costs\nPCV20 alone vs PCV15+PPSV23 in CMC, base case\nOutcomes and costPCV20 vs PCV15 + PPSV23\nTulane -CDC Merck Pfizera\nHealth \noutcomesIPD cases -26 -15 -5*\nPneumonia cases -780 -260 -1,100*\nAOM cases -30,000 -28,000 -4,900*\nDeaths -2 -1 -5*\nQALYs 200 140 120\nCosts\n($ millions)Vaccine costs -1 7 5\nCost of disease + sequelae -32 -23 -18\nTotal cost -33 -16 -12\nIn these assessments, \nall three models \nestimate higher health \nand lower total costsaThese are discounted values (rounded up to 2 significant figures) for the complete horizon for the base case of each model \n*Outcomes not reported as discounted values.\nNegative values indicate averted cases/deaths or reduced costs of PCV20, as compared to PCV15+PPSV23.\na.The Pfizer model does not directly assess policy question 2 but compares the receipt of PCV20 with and without PPSV23 to the receipt of PPSV23 on six -year -old \nchildren with a history of PCV13 vaccination. \nCost -effectiveness results, policy question\nbase case\nRisk group Intervention Comparator ModelCost per \nQALY\nCMCPCV20PCV13 + PPSV23 Tulane -CDC\n& \nMerck Cost -saving PCV15 +PPSV23\nPCV13 +PCV20 PCV13 + PPSV23 Pfizera\nICPCV20PCV13 + PPSV23 +PPSV23 Tulane -CDC\n&\nMerck Cost -saving PCV15 + PPSV23 + PPSV23\nPCV13 +PCV20 PCV13 + PPSV23 + PPSV23 Pfizera\naPfizer model had a different set of comparisons: in CMC: PCV13 (3+1) + PCV20 vs. PCV13 (3+1)+ PPSV23; in IC: PCV13 (3+1) + PCV20 vs. PCV13 (3+1)+ PPSV23 + PPSV23 ,because it started at age \n6.6.28\nSensitivity analyses policy question #2.1\nPCV20 alone vs PCV13/15+PPSV23\nCost -saving means lower costs and improved health outcomes in the intervention, as compared to the comparator.\n*Aside from the base case, no additional scenarios were conducted for this comparison.\naInthe scenarios where the Merck model assumed a re -emergence of IPD associated with certain serotypes that PCV20 missed the trial primary endpoint, PCV15 was found to be cost -saving relative to PCV20 (or \nPCV20 was dominated by PCV15).\nbPfizer model had a different set of comparisons: in CMC: PCV13 + PCV20  vs. PCV13(3+1)+ PPSV23; in IC: PCV13 + PCV20  vs. PCV13(3+1) + PPSV23 ,because it started at age 6.Risk \ngroupIntervention Comparator ModelRanges including sensitivity \nanalyses ($/QALY)\nCMCPCV20 PCV13 + PPSV23Tulane -CDC*Cost -saving\nMerck*Cost -saving\nPCV13 + PCV20 PCV13 + PPSV23 Pfizer Cost -savingb\nICPCV20 PCV13 + PPSV23 + PPSV23Tulane -CDC*Cost -saving\nMerck Cost -saving\nPCV13 + PCV20 PCV13 + PPSV23 + PPSV23 Pfizer Cost -savingb\nCMC\nPCV20PCV15 + PPSV23Tulane -CDC Cost -saving to $19,000\nMerck Cost -saving to dominateda\nIC PCV15 + PPSV23 + PPSV23Tulane -CDC Cost -saving\nMerck Cost -saving to dominateda\n29\nSensitivity analyses policy question #2.1\nPCV20 alone vs PCV13/15+PPSV23\nRisk \ngroupIntervention Comparator ModelRanges including sensitivity \nanalyses ($/QALY)\nCMCPCV20 PCV13 + PPSV23Tulane -CDC*Cost -saving\nMerck*Cost -saving\nPCV13 + PCV20 PCV13 + PPSV23 Pfizer Cost -savingb\nICPCV20 PCV13 + PPSV23 + PPSV23Tulane -CDC*Cost -saving\nMerck Cost -saving\nPCV13 + PCV20 PCV13 + PPSV23 + PPSV23 Pfizer Cost -savingb\nCMC\nPCV20PCV15 + PPSV23Tulane -CDC Cost -saving to $19,000\nMerck Cost -saving to dominateda\nIC PCV15 + PPSV23 + PPSV23Tulane -CDC Cost -saving\nMerck Cost -saving to dominateda\n30Cost -saving means lower costs and improved health outcomes in the intervention, as compared to the comparator.\n*Aside from the base case, no additional scenarios were conducted for this comparison.\naInthe scenarios where the Merck model assumed a re -emergence of IPD associated with certain serotypes that PCV20 missed the trial primary endpoint, PCV15 was found to be cost -saving relative to PCV20 (or \nPCV20 was dominated by PCV15).\nbPfizer model had a different set of comparisons: in CMC: PCV13 + PCV20  vs. PCV13(3+1)+ PPSV23; in IC: PCV13 + PCV20  vs. PCV13(3+1) + PPSV23 ,because it started at age 6.\nPolicy question 2.2\nPCV20 +PPSV23 series vs PCV20 alone among CMC/IC\nRisk \ngroupIntervention Comparator ModelCost per \nQALY\nCMCPCV20 + PPSV23 PCV20Tulane -CDC $4 million\nMerck $1.9 milliona\nPCV13 + PCV20 + PPSV23 PCV13+ PCV20 Pfizerb $6 million\nICPCV20 + PPSV23 +PPSV23 PCV20Tulane -CDC $690,000\nMerck $204,000a\nPCV13 + PCV20 + PPSV23 + \nPPSV23PCV13 + PCV20 Pfizerb $535,000\naValues calculated by presenter using results in Merck technical report.\nbPfizer model had a different set of comparisons: in CMC: PCV13 + PCV20  vs. PCV13(3+1)+ PPSV23; in IC: PCV13 + PCV20  vs. PCV13(3+1) + PPSV23 ,because it started at age 6. 32Cost -effectiveness results, policy question #2.2\nPCV20+ PPSV23 vs PCV20 alone, base case\nRisk \ngroupIntervention Comparator ModelCost per \nQALY\nCMCPCV20 + PPSV23 PCV20Tulane -CDC $4 million\nMerck $1.9 milliona\nPCV13 + PCV20 + PPSV23 PCV13+ PCV20 Pfizerb $6 million\nICPCV20 + PPSV23 +PPSV23 PCV20Tulane -CDC $690,000\nMerck $204,000a\nPCV13 + PCV20 + PPSV23 + \nPPSV23PCV13 + PCV20 Pfizerb $535,000\naValues calculated by presenter using results in Merck technical report.\nbPfizer model had a different set of comparisons: in CMC: PCV13 + PCV20  vs. PCV13(3+1)+ PPSV23; in IC: PCV13 + PCV20  vs. PCV13(3+1) + PPSV23 ,because it started at age 6. 33Cost -effectiveness results, policy question #2.2\nPCV20+ PPSV23 vs PCV20 alone, base case\nSummary\nSummary\n35Cost -saving means lower costs and improved health outcomes in the intervention, as compared to the comparator.•Policy question #1\n•Vaccination with PCV20 is expected to improve health outcomes \ncompared to PCV13 or PCV15.\n•Compared to PCV13 ,the Pfizer and Merck models estimated \nthat PCV20 would be cost -saving, whereas the Tulane -CDC model \nestimated a cost per QALY of $57,000.\n•Compared to PCV15 , the Pfizer model estimated that PCV20 \nwould be cost -saving, whereas the Tulane -CDC model and the \nMerck model estimated a cost per QALY of just over $100,000.\nSummary\n36•Policy question #2.1\n•Compared to PCV13/PCV15+PPSV23 series, PCV20 alone in CMC/IC \nwas estimated to be cost -saving in all but two scenarios investigated\n•Policy question #2.2\n•Compared to PCV20 alone , PCV20 +PPSV23 series in CM/IC was estimated to \ncost between $204,000 to $7 million dollars for each QALY gained \nCost -saving means lower costs and improved health outcomes in the intervention, as compared to the comparator.\nSummary\n37Cost -saving means lower costs and improved health outcomes in the intervention, as compared to the comparator.\nbAdditional details on these model inputs provided in supplemental slides.•Main differences across models appear to be related to indirect effects\n•bOther important factors: model structure, Vaccine effectiveness, QALY \nlosses due to disease\nThank you!Contributors\n•Miwako Kobayashi\n•Andrew Leidner\nSupplemental slides\n39\nReferences\n1. Stoecker C, Hampton LM, Link -Gelles R, Messonnier ML, Zhou F, Moore MR. Cost -effectiveness of using 2 vs 3 primary doses of 13 -valent \npneumococcal conjugate vaccine. Pediatrics. 2013;132(2):e324 -e32.\n2. Stoecker, Charles, Miwako Kobayashi, Almea Matanock, Bo -Hyun Cho, and Tamara Pilishvili. \"Cost -effectiveness of continuing \npneumococcal conjugate vaccination at age 65 in the context of indirect effects from the childhood immunization program.\" Vaccine 38, \nno. 7 (2020): 1770 -1777.\n3. Tong S, Amand C, Kieffer A, Kyaw MH. Trends in healthcare utilization and costs associated with pneumonia in the United States during \n2008 –2014. BMC Health Services Research. 2018 Dec;18(1):1 -8.\n4. Pfizer. CDC ABCs data (Data on File)\n5. Stoecker, Charles, Lee M. Hampton, Ruth Link -Gelles , Mark L. Messonnier, Fangjun Zhou, and Matthew R. Moore. \"Cost -effectiveness of \nusing 2 vs 3 primary doses of 13 -valent pneumococcal conjugate vaccine.\" Pediatrics 132, no. 2 (2013): e324 -e332.\n6. Pilishvili T. 2018a. “Estimating PCV13 direct and indirect effects on IPD among adults ≥65 years”. Presented at the meeting o f the Advisory \nCommittee on Immunization Practices, February 22, 2018. Atlant a, Georgia.\n7. Pilishvili T, Girke R, Xing W, Farley M, Schaffner W, Thomas A, Reingold A, Harrison L, Lynfield R, Zansky S, Petit S, Barnes M, Bareta J, Beal \nB, Shang N, Whitney C. 2018b. “Changes in invasive pneumococcal disease (IPD) among adults following 6 year s of 13 -valent \npneumococcal conjugate vaccine use in the U.S. ” Presented at the International Symposium on Pneumococci and Pneumococcal Diseases, \n2018. Melbourne, Australia .\n8. Prasad, Namrata, Charles Stoecker, Wei Xing, Bo -Hyun Cho, Andrew J. Leidner, and Miwako Kobayashi. \"Public health impact and cos t-\neffectiveness of 15 -valent pneumococcal conjugate vaccine use among the pediatric population of the United States.\" Vaccine 41, no. 18 \n(2023): 2914 -2921.\nHealth outcomes and cost resultsa\nPCV20 vs PCV15, base case\nPCV20 vs PCV15 PCV20 vs PCV13\nOutcomes and cost Tulane -CDC Merck++Pfizer\nHealth outcomesIPD cases -360 -400 -430*\nPneumonia cases -13,000 -2,300 -25,000*\nAOM cases -150,000 -201,000 -238,000*\nTotal deaths -160 -28 -93*\nQALYs 1,900 1,400 5,600\nCosts ($ millions)Cost of disease + sequelae -210 -180 NA\nVaccine costs 440 330 NA\nTotal cost 230 150 NA\n41aThese are discounted values (rounded up to 2 significant figures) for the complete horizon for the base case of each model \n*Outcomes not reported as discounted values.\nAll other values were discounted at 3%.\nNegative values indicate averted cases/deaths or reduced costs of PCV20, as compared to PCV15.\n++Pfizer  scenario analyses with single cohort and no indirect effects applied, and comparison is between PCV20 and PCV13\nModel assumptions: Selected base case assumptionsa\nPolicy question #1\nModel input Tulane -CDC Merck Pfizer\nVaccine effectiveness •lower VE for ST3 and \nST19F across all \nvaccines.\n•the serotype specific \nVEsin PCV20 were the \nsame as the serotype \nspecific VEs in PCV15 \nand PCV13 .•serotype specific VE \nwas lower in PCV20 for \nsix \nserotypes (3,12F,1,4,2\n3F,9V) than it was in \nPCV15.•the serotype specific \nVEsin PCV20 were the \nsame as the serotype \nspecific VEs in PCV15 \nand PCV13 .\nQALY loss due to \nhospitalized pneumonia in \nadults0.0105 0.071 0.13\nModel structure Single cohort (17 years) Single cohort (100 years) Multiple cohorts (10 \nyears)\naFrom the review, in addition to indirect effects, these assumptions appear to be the important in terms of determining differences between model results for policy question #1.\nFor added context, a QALY losses of 0.0016, 0.071 and 0.130 could be considered as representing a 32 -day hospitalization 59 -day hospitalization, respectively, where 20% health -related quality \nof life is experienced for the duration of hospitalization. 42\nDescription of models\nPolicy question #2\nModel characteristics Tulane -CDC MerckaPfizer\nCohort type Single birth cohort Single birth cohort Single -cohort (6 -year -olds)\n•~90 % have history of PCV13\nIndirect effects Yes (vaccinated CMC/IC contribute \nto indirect effect benefits)In scenarios only (not in base case) Yes (vaccinated CMC/IC experience \nreduced incidence)b\nVaccine coverage PCV (3rddose): 94 %\nPCV(4thdose): 82 %\ncPPSV23(1stdose): 78 %\ndPPSV23(2nddose): 64 %PCV (3+1): 93 %\nPPSV23(1stdose): 64 %\nPPSV23(2nddose): 53 %PCV20: 20%\nPPSV23: 20%\neWeighted\nvaccine price ($)PPSV23: 85 PPSV23: 91 PPSV23: 85\naThe Pfizer model does not directly assess policy question 2, but compares the receipt of PCV20 with and without PPSV23 to the rec eipt of PPSV23 on children with a history of PCV13 vaccination\nbIncidence among 6+ year olds was reduced after year 2, assuming routine use of PCV20 would occur, so VPD burden declines from routine use.\ncVaccine coverage of first PPSV23 dose is a percentage of those who got 4 doses of PCVs.\ndCoverage of second PPSV23 dose is a percentage of those who got the first PPSV23 dose.\neAllthree models used blended vaccine prices (combined using private and public market prices share weights which varied across t hemodels). 43\nSummary\n44Policy QuestionBase case estimates ($/QALY)\n*Range across all \nmodels Tulane -CDC Merck Pfizer\n1. PCV20 vs \nPCV13/PCV1557,000 to 125,000 Cost -saving to 105,000 Cost -saving Cost -saving to \ndominateda\n2.1 PCV20 alone (in \nCMC/IC)Cost -saving Cost -saving to \ndominateda\n2.2 PCV20+PPSV23 vs \nPCV20 (in CMC/IC)690,000 to 4 \nmillion204,000 to 1.9 million 535,000 to 6 million 204,000 to 7 million\nCost -saving means lower costs and improved health outcomes in the intervention, as compared to the comparator.\n*The ranges presented are obtained from the scenario analyses and probabilistic sensitivity analyses across all models\naThe Merck model found PCV15 was cost -saving relative to PCV20 (or PCV20 was dominated by PCV15) in scenarios where they assumed a r esurgence of specific PCV20 -only serotype IPD \ndisease.\nbAdditional details on these model inputs provided in supplemental slides.•Main differences across models appear to be related to indirect effects\n•bOther important factors: model structure, Vaccine effectiveness, QALY losses due to disease", "summary": "Summary of three economic analyses of the use of  20-valent pneumococcal conjugate vaccine (PCV20)  in children in the United States Diepreye V. Ayabina Division of Bacterial Diseases CDC/NCIRDAdvisory Committee on Immunization Practices  June 22, 2023 Acknowledgements •This presentation summarizes work conducted by three modeling teams •Tulane -CDC team •Charles Stoecker (Tulane University), Miwako Kobayashi (CDC), Andrew Leidner (CDC), Diepreye Ayabina •Pfizer team •Mark Rozenbaum , Liping…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/03-Pneumococcal-Ayabina-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 44}
{"title": "04 Pneumococcal Kobayashi 508", "content": "Evidence to Recommendations Framework and Policy Options: \nUse of 20 -valent Pneumococcal Conjugate Vaccine in U.S. Children\nMiwako Kobayashi, MD, MPH\nPneumococcal Vaccines Work Group\nAdvisory Committee on Immunization Practices\nJune 22, 2023National Center for Immunization & Respiratory Diseases\nPICO \nQuestionShould PCV20 be recommended as an option for pneumococcal vaccination \nfor U.S. children?\nPopulation All U.S. children aged <2 yearsU.S. children aged 2 –18 years with \nunderlying medical conditions\nInterventionPCV20 according to currently \nrecommended dosing and \nschedulesPCV20 (without PPSV23)\nComparison PCV13 or PCV15 according to currently recommended dosing and schedules\nOutcomesVT-IPD, VT -pneumonia, VT -AOM, VT -pneumococcal deaths, serious adverse \nevents following vaccination\nVT: vaccine -type, IPD: invasive pneumococcal disease, AOM: acute otitis media2\nPICO \nQuestionShould PCV20 be recommended as an option for pneumococcal vaccination \nfor U.S. children?\nPopulation All U.S. children aged <2 yearsU.S. children aged 2 –18 years with \nunderlying medical conditions\nInterventionPCV20 according to currently \nrecommended dosing and \nschedulesPCV20 (without PPSV23)\nComparison PCV13 or PCV15 according to currently recommended dosing and schedules\nOutcomesVT-IPD, VT -pneumonia, VT -AOM, VT -pneumococcal deaths, serious adverse \nevents following vaccination\nVT: vaccine -type, IPD: invasive pneumococcal disease, AOM: acute otitis media3\nPICO \nQuestionShould PCV20 be recommended as an option for pneumococcal vaccination \nfor U.S. children?\nPopulation All U.S. children aged <2 yearsU.S. children aged 2 –18 years with \nunderlying medical conditions\nInterventionPCV20 according to currently \nrecommended dosing and \nschedulesPCV20 (without PPSV23)\nComparison PCV13 or PCV15 according to currently recommended dosing and schedules\nOutcomesVT-IPD, VT -pneumonia, VT -AOM, VT -pneumococcal deaths, serious adverse \nevents following vaccination\nVT: vaccine -type, IPD: invasive pneumococcal disease, AOM: acute otitis media4\nRisk group/Condition\nChildren without immunocompromising conditions\nChronic heart disease†\nChronic kidney disease (excluding maintenance dialysis and nephrotic syndrome, which are included in \nimmunocompromising conditions)\nChronic liver disease\nChronic lung disease (including moderate persistent or severe persistent asthma)\nDiabetes mellitus\nCerebrospinal fluid leak\nCochlear implant\nChildren with immunocompromising conditions\nOn maintenance dialysis or nephrotic syndrome\nCongenital or acquired asplenia, or splenic dysfunction\nCongenital or acquired immunodeficiency¶\nDiseases and conditions treated with immunosuppressive drugs or radiation therapy**\nHIV infection\nSickle cell disease or other hemoglobinopathies\nSolid organ transplant\n†Recommendations are of particular importance for children with cyanotic congenital heart disease and cardiac failure.\n¶Includes B -(humoral) or T -lymphocyte deficiency; complement deficiencies, particularly C1, C2, C3, and C4 deficiency; and phago cytic disorders (excluding chronic granulomatous disease).\n** Including malignant neoplasms, leukemias, lymphomas, and Hodgkin disease.5\nRisk group/Condition\nChildren without immunocompromising conditions\nChronic heart disease†\nChronic kidney disease (excluding maintenance dialysis and nephrotic syndrome, which are included in \nimmunocompromising conditions)\nChronic liver disease\nChronic lung disease (including moderate persistent or severe persistent asthma)\nDiabetes mellitus\nCerebrospinal fluid leak\nCochlear implant\nChildren with immunocompromising conditions\nOn maintenance dialysis or nephrotic syndrome\nCongenital or acquired asplenia, or splenic dysfunction\nCongenital or acquired immunodeficiency¶\nDiseases and conditions treated with immunosuppressive drugs or radiation therapy**\nHIV infection\nSickle cell disease or other hemoglobinopathies\nSolid organ transplant\n†Recommendations are of particular importance for children with cyanotic congenital heart disease and cardiac failure.\n¶Includes B -(humoral) or T -lymphocyte deficiency; complement deficiencies, particularly C1, C2, C3, and C4 deficiency; and phago cytic disorders (excluding chronic granulomatous disease).\n** Including malignant neoplasms, leukemias, lymphomas, and Hodgkin disease.6\nRisk group/Condition\nChildren without immunocompromising conditions\nChronic heart disease†\nChronic kidney disease (excluding maintenance dialysis and nephrotic syndrome, which are included in \nimmunocompromising conditions)\nChronic liver disease\nChronic lung disease (including moderate persistent or severe persistent asthma)\nDiabetes mellitus\nCerebrospinal fluid leak\nCochlear implant\nChildren with immunocompromising conditions\nOn maintenance dialysis or nephrotic syndrome\nCongenital or acquired asplenia, or splenic dysfunction\nCongenital or acquired immunodeficiency¶\nDiseases and conditions treated with immunosuppressive drugs or radiation therapy**\nHIV infection\nSickle cell disease or other hemoglobinopathies\nSolid organ transplant\n†Recommendations are of particular importance for children with cyanotic congenital heart disease and cardiac failure.\n¶Includes B -(humoral) or T -lymphocyte deficiency; complement deficiencies, particularly C1, C2, C3, and C4 deficiency; and phago cytic disorders (excluding chronic granulomatous disease).\n** Including malignant neoplasms, leukemias, lymphomas, and Hodgkin disease.7\nRationale for updating indications for risk -based \nrecommendations\n▪Improve harmonization between pediatric and adult recommendations\n▪Data supporting increased risk of pneumococcal disease in this population\n•Increased pneumococcal pneumonia1or IPD1,2risk in children with \nasthma without long -term oral corticosteroid use\n•Increased risk of IPD in children with chronic kidney disease \n(regardless of stage)2,3\n•Increased pneumococcal pneumonia2or IPD2,4risk in children with \nchronic liver disease\nIPD=invasive pneumococcal disease\n1. Talbot et al. NEJM 2005 . Long -term oral corticosteroid use of ≥120 days defined as high risk\n2. Pelton et al. CID 2014. Long -term oral corticosteroid use of ≥30 days defined as severe asthma\n3. Hjuler et al. Pediatrics 2008. \n4. Van Hoek et al. Journal of Infection 2012\nValuesEvidence to Recommendations ( EtR) framework\nEtRDomain Question\nPublic Health Problem •Is the problem of public health importance?\nBenefits and Harms •How substantial are the desirable anticipated effects?\n•How substantial are the undesirable anticipated effects?\n•Do the desirable effects outweigh the undesirable effects?\n•What is the overall certainty of this evidence for the critical outcomes?\n•Does the target population feel the desirable effects are large relative \nto the undesirable effects?\n•\nEquity •Is there important variability in how patients value the outcomes?\nAcceptability •Is the intervention acceptable to key stakeholders?\nFeasibility •Is the intervention feasible to implement?\nResource Use •Is the intervention a reasonable and efficient allocation of resources?\nWhat would be the impact of the intervention on health equity?9\nEvidence to Recommendations ( EtR) framework\nEtRDomain Question\nPublic Health Problem •Is the problem of public health importance?\nBenefits and Harms •How substantial are the desirable anticipated effects?\n•How substantial are the undesirable anticipated effects?\n•Do the desirable effects outweigh the undesirable effects?\n•What is the overall certainty of this evidence for the critical outcomes?\nValues •Does the target population feel the desirable effects are large relative \nto the undesirable effects?\n•Is there important variability in how patients value the outcomes?\nAcceptability •Is the intervention acceptable to key stakeholders?\nFeasibility •Is the intervention feasible to implement?\nResource Use •Is the intervention a reasonable and efficient allocation of resources?\nEquity •What would be the impact of the intervention on health equity?10\nEtRDomain: Public Health Problem\nPneumococcal disease epidemiology in children\n•Use of PCVs (PCV7, PCV13) significantly decreased the incidence of \npneumococcal disease in U.S. children.\n•Outpatient ARIs caused by pneumococcus, such as AOM, sinusitis, and \npneumonia, are common causes of outpatient visits and antibiotic prescribing. \n•Estimated incidence of outpatient visits and antibiotic prescriptions \nattributable to PCV20, non -PCV13 serotypes: 4–5 times PCV15, non -PCV13\n•In 2018 –2019, the proportion of IPD caused by vaccine serotypes was:\n•PCV20, non -PCV13: ~30% of IPD\n•PCV15, non -PCV13: ~15% of IPD\n•PPSV23, non -PCV20: 1 –5% of IPD\n•Risk of pneumococcal disease remains high in children with underlying \nconditions that increase the risk of pneumococcal disease.\nAOM=acute otitis media; ARI= acute respiratory illness; IPD=invasive pneumococcal disease  \nGierke. February 2023 ACIP meeting presentation\nKing. February 2023 ACIP meeting presentation12\nMonthly IPD rates (per 100,000) among children aged \n<5 years old, 2018 –2022\n0.000.200.400.600.801.001.201.40\nJan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec2018 2019 2020 2021 2022 *\nIPD=invasive pneumococcal disease\nCDC ABCs unpublished data. *2022 estimates are preliminar y13\nPublic Health Problem\nIs pneumococcal disease of public health importance in U.S. \nchildren? \n□\n□\n□\n□\n□\n□No \nProbably no\nProbably yes\nYes\nVaries\nDon’t know\n14\nEtRDomain: Benefits and Harms\nSummary of evidence: Benefits, children <2 years \n•Informed by 2 randomized controlled trials (Phase II and III)1,2\n•Healthy children randomized to either PCV13 or PCV20\n•PCVs given using 3+1 schedule\n•Summary of findings\n•PCV20 had numerically lower IgG geometric mean concentrations vs. PCV13 \nfor the 13 shared serotypes\n•Post dose 3 : \n•PCV20 did not meet noninferiority criteria* vs. PCV13 for serotypes 1, 3, 4, 9V, 23F, and \n12F*** for one of the outcomes \n•Post dose 4 : \n•PCV20 noninferior **to PCV13 for all 13 shared serotypes \n•PCV20 noninferior to PCV13*** for all 7 additional serotypes\n*Measured as lower bound of 2 -sided 95% CI for percent difference proportion of participants (PCV20 -PCV13) meeting IgG threshold value of >=0.35μg/mL for all serotypes except ≥ \n0.23 μg/mL, ≥ 0.10 μg/mL and ≥ 0.12μg/mL for serotypes 5, 6B and 19A respectively\n**Measured as lower bound of 2 -sided 95% CI for IgG geometric mean concentration ratio (PCV20/PCV13) >0.5 \n***Compared with the serotype with lowest immune response among PCV13 serotypes except for serotype 3\n1. Senders et al. PIDJ 2021\n2. Pfizer unpublished data from B747101116\nSummary of evidence: Safety, children <2 years \n•Serious adverse events (SAEs) across 3 studies (dose 1 through 6 months after \ndose 4)1-3:\n•PCV20: 4.5% (101 of 2,232) vs PCV13: 3.7% (64 of 1,717)\n•None were considered to be vaccine -related\n1. Senders et al. PIDJ 2021\n2. Pfizer B7471011, https://www.fda.gov/media/149987/download\n3. Pfizer B7471013, https://www.fda.gov/media/149987/download17\nShould PCV20 be recommended as an option for pneumococcal conjugate \nvaccination according to currently recommended dosing and schedules, for U.S. \nchildren aged <2 years?\nType Outcome ImportanceIncluded in \nevidence profileCertainty of \nevidence\nBenefitsVT-IPD Critical Yes Moderate\nVT-pneumonia Critical Yes Moderate\nVT-AOM Critical Yes Moderate\nVT-pneumococcal \ndeathsCritical Yes Moderate\nHarmsSAEs following \nvaccinationCritical Yes Moderate\nAOM=acute otitis media, IPD=invasive pneumococcal disease, SAE=serious adverse events, VT=vaccine -type18\nSummary of evidence: \nBenefits, children 2 –18 years with underlying conditions \n•No studies conducted among children with underlying medical conditions\n•Informed by 1 non -randomized trial (Phase III), no comparator\n•Healthy children aged 15 months to 17 years received a dose of PCV20\n•Children aged <5 years received ≥3 doses of PCV13\n•Summary of findings\n•PCV20 was immunogenic * for all 20 vaccine serotypes 1 month after \nvaccination vs. pre-vaccination. \n*Measured as IgG GMCs and GMFR and OPA GMFRs\nPfizer unpublished data from B747101419\nSummary of evidence: \nSafety, children 2 –18 years with underlying conditions\n•Serious adverse events (SAEs) :\n•PCV20: 0.6% (5/831) \n•None were considered to be vaccine -related\nPfizer unpublished data from B747101420\nShould PCV20 without PPSV23 be recommended as an option for pneumococcal \nvaccination for U.S. children aged 2– 18 years with underlying medical conditions that \nincrease the risk of pneumococcal disease?\nType Outcome ImportanceIncluded in evidence \nprofile Certainty of evidence\nBenefitsVT-IPD Critical Yes Very Low\nVT-pneumonia Critical Yes Very Low\nVT-AOM Critical Yes Very Low\nVT-pneumococcal \ndeathsCritical Yes Very Low\nHarmsSAEs following \nvaccinationCritical Yes Very Low\nAOM=acute otitis media, IPD=invasive pneumococcal disease, SAE=serious adverse events, VT=vaccine -type21\n□\n□\n□\n□\n□\n□Minimal\nSmall\nModerate\nLarge\nVaries\nDon’t knowBenefits and Harms\nHow substantial are the desirable anticipated effects?\n▪Routine PCV20 use for children aged <2 years\n▪PCV20 without PPSV23 for children aged 2 –18 years with underlying conditions \n•PCV20 provides the broadest serotype coverage among available \nPCVs.\n•Unknown how substantial the protection conferred from PCV20 will \nbe based on available data. \n•No PCV20 data among children with underlying medical conditions .\n22\nBenefits and Harms\nHow substantial are the undesirable anticipated effects?\n▪Routine PCV20 use for children aged <2 years\n▪PCV20 without PPSV23 for children aged 2 –18 years with underlying conditions \n□\n□Minimal\nSmall\n□Moderate\n□Large\n□Varies\n□Don’t know\n23\nBenefits and Harms\nDo the desirable effects outweigh the undesirable effects?\n▪Routine PCV20 use for children aged <2 years\n▪PCV20 without PPSV23 for children aged 2 –18 years with underlying conditions \n□\n□\n□Favors intervention*\nFavors current recommendation\nFavors both\n□Favors neither\n□Varies\n□Don’t know*Intervention: PCV20 use\nComparison: \n•Children <2 years: PCV13 or PCV15 use\n•Children 2 –18 years with underlying \nconditions: PPSV23 use after currently \nrecommended PCV (PCV13 or PCV15) \ndoses\n24\nEtRDomain: Equity\nSummary of evidence \n•Disparities in pneumococcal vaccine coverage by race/ethnicity, insurance coverage, \nand poverty level exist1\n•Nationally representative PPSV23 vaccine coverage data among children with \nindications are limited2–5\n•Range ~20 –60%, many reports from single institution \n•Disparities in IPD rates by race and the percentage of census tract poverty remain6,7\n•Most of the remaining disparities were due to serotypes not included in PCV20\n1. ChildVaxView Interactive Child Vaccination Coverage | CDC\n2. Reeves et al. Pediatric Blood & Cancer, 2018\n3. Tran et al. Frontiers in Pediatrics, 2021\n4. Mirza et al. The Ochsner Journal, 2022\n5. Harris et al. Pediatrics, 2022\n6. Farrar February 2022 ACIP meeting presentation\n7. Kobayashi February 2023 ACIP meeting presentation26\nEquity\nWhat would be the impact of recommending PCV20 for U.S. \nchildren on health equity?\n□\n□\n□Reduced\nProbably reduced\nProbably no impact\n□Probably increased\n□Increased\n□Varies \n□Don’t know \n27\nEquity\nWhat would be the impact of recommending PCV20 for U.S. \nchildren aged <2 years on health equity?\nProbably reduced:\n•New interventions are likely to be accessible to wealthy communities, first \n→VFC program mitigates inequities in access to recommended vaccines \nProbably no impact:\n•Remaining disparities in vaccine -type disease seem to be minimal \nProbably increased:\n•Post -PCV13 data showed that PCV13 reduced disparities in vaccine -type disease \nVFC=Vaccines for Children28\nEquity\nWhat would be the impact of recommending PCV20 without \nPPSV23 for U.S. children aged 2 –18 years with underlying \nmedical conditions on health equity?\nProbably no impact:\n•Risk-based recommendation is less likely to be equitable compared with routine \nvaccine recommendations. \nProbably increased:\n•PCV20 use without PPSV23 could simplify the pneumococcal vaccine \nrecommendations and improve vaccine coverage. \n29\nEtRDomain: Values and Preferences\nValues and Preferences\nCriterion 1: Does the target population feel that the desirable \neffects from vaccination are large relative toundesirable effects?\n▪Routine PCV20 use for children aged <2 years\n•Probably Yes\n▪PCV20 without PPSV23 for children aged 2 –18 years with \nunderlying conditions\n•Probably Yes/Yes\n31\nValues and Preferences\nCriterion 2: Is there important uncertainty about, or variability \nin, how much people value the main outcomes?\n•Routine PCV20 use for children aged <2 years\n•Probably important/not important uncertainty or \nvariability\n•PCV20 without PPSV23 for children aged 2 –18 years with \nunderlying conditions\n•Probably not important uncertainty or variability\n32\nValues and Preferences\nUncertainties:\n▪No data assessing the public’s perception of PCV20\n▪No data assessing efficacy/effectiveness of PCV20 against disease\n▪Benefits from PCV20 use alone without PPSV23 for children with \nunderlying conditions are uncertain\nProbably not important uncertainty or variability:\n▪>90% vaccine coverage for ≥3 PCV doses in children by age 24 months1\n▪Increased cases of invasive pneumococcal disease (late 2022): caregivers of \nthe child will likely value the use of PCV20\n1.Hill et al. MMWR 2023.33\nEtRDomain: Acceptability\nThree healthcare provider surveys\n▪Web -based surveys among providers who administer pneumococcal \nvaccines to children\n•1 by Pfizer (manufacturer of PCV13 and PCV20)1\n•2 by Merck (manufacturer of PCV15 and PPSV23)2,3\n1. Myers K, Pierce N, Poulos C, Arguedas A, Chilson E, Hauber B, et al. US Health Care Providers' Preferences for Pediatric Pneumococcal Conjugate Vaccines. Preliminary Findings. 2023.\n2. OPEN Health. Provider Knowledge, Attitude, and Preferences Towards Pediatric Pneumococcal Vaccines. 2023.\n3. Merck & Co. Inc. HCP Preferences Concerning Pediatric Pneumococcal Vaccines Report. 2023. 35\nKey findings ( Pfizer survey )\nVaccine profiles of PCV15 and PCV20 shown, emphasizing IPD serotype coverage.\nChildren aged <2 years with incomplete series:\n▪76% of providers responded that they would transition patients who started their PCV \nseries with either PCV13 or PCV15 to PCV20\n•To provide protection against as many serotypes as possible ( 94% ). \nChildren with underlying conditions:\n▪43% of providers responded that PCV20 alone without PPSV23 should be \nrecommended.\n•Prefer/store only 1 vaccine instead of multiple vaccines ( 61% ).\n•Prefer conjugated vaccines over unconjugated polysaccharide vaccines ( 48% ). \n1. Myers K, Pierce N, Poulos C, Arguedas A, Chilson E, Hauber B, et al. US Health Care Providers' Preferences for Pediatric Pneumococcal Conjugate Vaccines. Preliminary Findings. 2023.\n36\nKey findings ( Merck surveys )\n▪Importance of pneumococcal vaccination\n•>90% of providers believed that it is important to administer \npneumococcal vaccines to children aged <2 years.1\n▪Important vaccine attributes\n•≥90% of providers believed that it is important to have product -specific \ndata for immunocompromised or premature children.1\n•Of the five vaccine attributes assessed for hypothetical vaccines, immune \nresponse for the serotypes covered in PCV13 was given the highest \nimportance.2\n1. Merck & Co. Inc. HCP Preferences Concerning Pediatric Pneumococcal Vaccines Report. 2023..\n2. OPEN Health. Provider Knowledge, Attitude, and Preferences Towards Pediatric Pneumococcal Vaccines. 2023.37\nAcceptability\nIs recommending PCV20 acceptable to key stakeholders?\n▪Routine PCV20 use for children aged <2 years\n•Yes\n▪PCV20 without PPSV23 for children aged 2 –18 years with \nunderlying conditions\n•Probably Yes/Yes\n•Simplifies storage, less prone to vaccine administration errors\n•Some providers may not feel comfortable recommending PCV20 alone without \nPPSV23\n38\nEtRDomain: Resource Use\nSummary of evidence\n•Routine PCV20 use vs. PCV13 or PCV15 in children aged <2 years\n•Base case ranged from cost -saving to $125,000 per QALY gained\n•Differences across models related to indirect effects on adult disease\n•PCV20 alone without PPSV23 use in children aged 2 –18 years with underlying \nconditions\n•PCV20 alone instead of PCV13/PCV15+PPSV23* was found to be cost -saving \nin most model scenarios\n•Addition of PPSV23 to PCV20 had high cost per QALY gained\n•Greater than $1.9 million per QALY gained among CMC\n•Between $200,000 to $690,000 per QALY gained among IC\nCMC=chronic medical conditions, including chronic heart, lung, and liver disease, diabetes\nIC=immunocompromising conditions, including chronic renal failure, nephrotic syndrome, immunodeficiency, iatrogenic immunosuppression, generalized malignancy, HIV, \nHodgkin disease, leukemia, lymphoma, solid organ transplants, cochlear implants, CSF leaks, congenital or acquired asplenia, sic kle cell disease, or other hemoglobinopathies\nQALY= quality -adjusted life -years\n*CMC received 1 dose of PPSV23, IC received 2 doses of PPSV2340\n□\n□No \nProbably no\n□Probably yes\n□Yes\n□Varies\n□Don’t knowResource Use\nIs the option a reasonable and efficient allocation of resources?\n▪Routine PCV20 use for children aged <2 years\n▪PCV20 without PPSV23 for children aged 2 –18 years with underlying conditions \nYes:\n•Protects against more pneumococcal serotypes.\nMinority opinion :\n•Expensive vaccine.\n•Uncertainties in the effectiveness remain.\n•Onlyimmunogenicity data.\n•No PCV20 data from children with underlying conditions.\n•Challenging to interpret cost -effectiveness analyses findings that \nuse different methods and assumptions (routine PCV20 use).\n•Sensitive to launch price.\n41\nEtRDomain: Feasibility\n□\n□No \nProbably no\n□Probably yes\n□Yes\n□Varies\n□Don’t knowFeasibility\nIs recommending PCV20 feasible to implement?\n▪Routine PCV20 use for children aged <2 years\n▪PCV20 without PPSV23 for children aged 2 –18 years with underlying conditions \nRoutine PCV20 use for children aged <2 years:\n•PCVs have been recommended for >20 years.\nPCV20 without PPSV23 for children with underlying conditions:\n•Simpler, streamlined recommendation.\n•More feasible in general and are more likely to be followed in \nclinical practice.\n43\nEtRDomains PCV20, <2 years (routine) PCV20, 2 –18 years old \nPublic Health Problem Yes\nBenefits and Harms\na. Benefits Moderate\nb. Harms Minimal\nc. Benefit>Harm? Favors intervention/Favors both (split)\nd. Overall certainty: effectiveness 2 (moderate) 4 (very low)\ne. Overall certainty: safety 2 (moderate) 4 (very low)\nValues\na. Desirable>Undesirable? Probably yes Probably yes/yes (split)\nb. Uncertainty? Probably important uncertainty or \nvariability/Probably no important uncertainty or \nvariability (split)Probably no important uncertainty or variability\nAcceptability Yes Probably yes/yes (split)\nResource Use Yes\nEquity Probably increased (different opinions)\nFeasibility YesSummary of Work Group Interpretation of the EtRDomains ( Updated )\n44\nSummary: Work Group Interpretations\nShould PCV20 be recommended as an option for pneumococcal conjugate \nvaccination according to currently recommended dosing and schedules for \nU.S. children aged <2 years ? \nComparison: PCV13 or PCV15 \nBalance of \nconsequencesUndesirable \nconsequences \nclearly \noutweigh \ndesirable \nconsequences \nin most \nsettingsUndesirable \nconsequences \nprobably \noutweigh \ndesirable \nconsequences \nin most \nsettingsThe balance \nbetween \ndesirable and \nundesirable \nconsequences \nis closely \nbalanced or \nuncertainDesirable \nconsequences \nprobably \noutweigh \nundesirable \nconsequences \nin most \nsettingsDesirable \nconsequences \nclearly \noutweigh \nundesirable \nconsequences \nin most \nsettingsThere is \ninsufficient \nevidence to \ndetermine the \nbalance of \nconsequences\nSummary: Work Group Interpretations\nShould PCV20 be recommended as an option for pneumococcal conjugate \nvaccination according to currently recommended dosing and schedules for \nU.S. children aged <2 years ? \nIn support of recommending PCV20:\n•Additional serotypes covered by PCV20 areexpected to prevent additional disease.\nIn support of recommending both PCV20 and PCV15*:\n•We only have immunogenicity study data for both PCV20 and PCV15, clinical \nimplications are unknown.\n•Range in cost -effectiveness analysis findings. \n•Good to have options for PCVs, in case of challenges with/delays in access to PCV20.\n*PCV13 expected to be removed from market after a transition period\nSummary: Work Group Interpretations\nShould PCV20 without PPSV23 be recommended as an option for children \naged 2–18 years with underlying medical conditions that increase the risk \nof pneumococcal disease?\nComparison: PCV13 or PCV15 + PPSV23 according to current dosing \n/schedule  \nBalance of \nconsequencesUndesirable \nconsequences \nclearly \noutweigh \ndesirable \nconsequences \nin most \nsettingsUndesirable \nconsequences \nprobably \noutweigh \ndesirable \nconsequences \nin most \nsettingsThe balance \nbetween \ndesirable and \nundesirable \nconsequences \nis closely \nbalanced or \nuncertainDesirable \nconsequences \nprobably \noutweigh \nundesirable \nconsequences \nin most \nsettingsDesirable \nconsequences \nclearly \noutweigh \nundesirable \nconsequences \nin most \nsettingsThere is \ninsufficient \nevidence to \ndetermine the \nbalance of \nconsequences\nSummary: Work Group Interpretations\nShould PCV20 without PPSV23 be recommended as an option for children \naged 2 to 18 years with underlying medical conditions that increase the \nrisk of pneumococcal disease?\nIn support of recommending PCV20 without PPSV23:\n•Simplicity of PCV20 use without PPSV23, ease of vaccine storage.\n•Immunologic advantages of PCVs over PPSV23.\n•PCV20 provides the broadest serotype coverage among available PCVs.\nIn support of recommending BOTH PCV20 without PPSV23 AND PCV15* + PPSV23:\n•No data on PCV20 use in children with underlying medical conditions.\n•Harmonization with the updated adult pneumococcal vaccine recommendations \n(October 2022 ACIP meeting).\n*PCV13 expected to be removed from market after a transition period\nProposed Policy Options for a Vote\n1. Routine PCV use for all children aged <24 months\nUse of either PCV15 or PCV20 is recommended for all children aged 2 –23 \nmonths according to currently recommended PCV dosing and schedules. \n50\nAge at visit/\nHealth statusNo. of previous PCV13/PCV15/PCV20 \ndoses received Recommended PCV15 /PCV20 regimen†\nAll children (healthy and those with risk conditions)\n2–6 mos13 additional doses: 2 doses, 8 wks apart; last dose at age \n12–15 mos\n22 additional doses: 1 dose 8 wks after most recent dose; \nlast dose ≥8 wks later at age 12 –15 mos\n3 1 additional dose at age 12 –15 mos\n7–11 mos\n1 or 2 (at age <7 mos) 2 additional doses: 1 dose 8 wksafter most recent dose; \nlast dose ≥8 wkslater at age 12 –15 mos\n3 (at age <7 mos) 1 additional dose at age 12 –15 mos\n1 (at age ≥7 mos)2 additional doses: 1 dose 8 wksafter most recent dose; \nlast dose ≥8 wkslater at age 12 –15 mos\n2 (at age ≥7 mos) 1 additional dose at age 12 –15 mos\n12–23 mos1 (at age <12 mos)2 additional doses: 1 dose ≥8 wksafter most recent dose; \nlast dose ≥8 wkslater\n2 or 3 (at age <12 mos) 1 additional dose, ≥8 wks after most recent dose\n1 (at age ≥12 mos) 1 additional dose, ≥8 wksafter most recent dose†\n†Minimum interval between doses is 8 weeks except for children vaccinated at age <1 year, for whom minimum interval between do ses is 4 weeks.\n51\n2. Catch -up PCV doses for children aged 24 –71 months \nwith an incomplete PCV vaccination status\nFor healthy children aged 24 –59 months or through age 71 months \nfor children with any underlying condition that increases the risk of \npneumococcal disease (hereafter, risk condition)* with an incomplete \nPCV vaccination status , use of either PCV15 or PCV20 according to \ncurrently recommended PCV dosing and schedules isrecommended. \n*Risk conditions include: cerebrospinal fluid leak; chronic heart disease ; chronic kidney disease (excluding maintenance dialysis and nephrotic syndrome, which are included in \nimmunocompromising conditions); chronic liver disease; chronic lung disease (including moderate persistent or severe persiste nt asthma ); cochlear implant; diabetes mellitus; \nimmunocompromising conditions ( on maintenance dialysis or with nephrotic syndrome; congenital or acquired asplenia or splenic dysfunction; congenital or acquired \nimmunodeficiencies; diseases and conditions treated with immunosuppressive drugs or radiation therapy, including malignant ne oplasms, leukemias, lymphomas, Hodgkin disease, and \nsolid organ transplant; HIV infection; and sickle cell disease and other hemoglobinopathies).52\nRisk group/Condition\nChildren without immunocompromising conditions\nChronic heart disease†\nChronic kidney disease (excluding maintenance dialysis and nephrotic syndrome, which are included in \nimmunocompromising conditions)\nChronic liver disease\nChronic lung disease (including moderate persistent or severe persistent asthma)\nDiabetes mellitus\nCerebrospinal fluid leak\nCochlear implant\nChildren with immunocompromising conditions\nOn maintenance dialysis or nephrotic syndrome\nCongenital or acquired asplenia, or splenic dysfunction\nCongenital or acquired immunodeficiency¶\nDiseases and conditions treated with immunosuppressive drugs or radiation therapy**\nHIV infection\nSickle cell disease or other hemoglobinopathies\nSolid organ transplant\n†Recommendations are of particular importance for children with cyanotic congenital heart disease and cardiac failure.\n¶Includes B -(humoral) or T -lymphocyte deficiency; complement deficiencies, particularly C1, C2, C3, and C4 deficiency; and phago cytic disorders (excluding chronic granulomatous disease).\n** Including malignant neoplasms, leukemias, lymphomas, and Hodgkin disease.53\nAge at visit/\nHealth statusNo. of previous PCV13/PCV15/PCV20 \ndoses received Recommended PCV15/ PCV20 regimen†\nHealthy Children\n24–59 mos No previous doses or any incomplete \nschedule by 24 mos1 additional dose, ≥8 wks after most recent dose\n5–18 yrs No previous doses or any incomplete \nschedule by 24 mosNo additional dose\nChildren with risk conditions\n24–71 mos No previous doses or any incomplete \nschedule and <3 doses by age 24 mos2 doses: 1 dose ≥8 wks after most recent dose; last \ndose ≥8 wks later\n3 (all at age <12 mos) 1 additional dose, ≥8 wks after most recent dose\n†Minimum interval between doses is 8 weeks except for children vaccinated at age <1 year, for whom minimum interval between do ses is 4 weeks.\n54\n3. Children aged 2 –18 years with any risk condition who have \ncompleted their recommended PCV doses before age 6 years\nFor children aged 2 –18 years with any risk condition who have \nreceived all recommended doses before age 6 years\n•Using ≥1 dose of PCV20: No additional doses of any pneumococcal \nvaccine are indicated. This recommendation may be updated as \nadditional data become available.  \n•Using PCV13 or PCV15 (no PCV20): A dose of PCV20 or PPSV23 using \npreviously recommended doses and schedule is recommended. \n55\nChildren aged 2 –18 years with CMC, CSF leak, or cochlear implant \nwho have received all recommended PCV doses before age 6 years, \ncurrent recommendations\nCMC=chronic medical conditions, including chronic kidney disease (excluding maintenance dialysis and nephrotic syndrome, whic h are included in \nimmunocompromising conditions), chronic heart disease, chronic liver disease, chronic lung disease (including moderate persis tent or severe persistent asthma), \ndiabetes mellitus; CSF=cerebrospinal fluidPPSV23Complete with \neither PCV13/15≥8 weeks\n56\nChildren aged 2 –18 years with CMC, CSF leak, or cochlear implant \nwho have received all recommended PCV doses before age 6 years, \nproposed recommendations\nCMC=chronic medical conditions, including chronic kidney disease (excluding maintenance dialysis and nephrotic syndrome, whic h are included in \nimmunocompromising conditions), chronic heart disease, chronic liver disease, chronic lung disease (including moderate persis tent or severe persistent asthma), \ndiabetes mellitus; CSF=cerebrospinal fluidPPSV23≥8 weeks Complete with \neither PCV13/1 5PCV20Complete with \nany PCV20 doseScenario 1PCV vaccination status\nNo additional doses \nindicated\nOption 1Scenario 2\n≥8 weeksOption 2\n57\nChildren with an immunocompromising condition aged 2 –18 years \nwho have completed PCV doses before age 6 years, current \nrecommendations\nIC= immunocompromising conditionPPSV23 PPSV23\n≥5 yearsComplete with \neither PCV13/15 ≥8 weeks\n58\nChildren with an immunocompromising condition aged 2 –18 years \nwho have completed PCV doses before age 6 years, proposed \nrecommendations\nIC= immunocompromising conditionPPSV23≥8 weeks\nPCV20Complete with \nany PCV20 dose\nPPSV23≥5 yearsScenario 1\nPPSV23\n≥8 weeksComplete with \neither PCV13/15 ≥5 yearsPCV20\n≥8 weeksOption 3Option 1\nOption 2No additional doses \nindicatedScenario 2PCV vaccination status\nNo additional doses \nindicated\n59\n4. Children aged 6 –18 years with any risk condition \nwho have not received any dose of PCV\nFor children aged 6 –18 years with any risk condition who have not \nreceived any dose of PCV13, PCV15, or PCV20, a single dose of PCV15 \nor PCV20 is recommended at least 8 weeks after the most recent dose \nof pneumococcal vaccine. When PCV15 is used, it should be followed \nby a dose of PPSV23 at least 8 weeks later if not previously given. \n60\nCurrent risk-based pneumococcal vaccine recommendations for PCV \nunvaccinated children aged 6 –18 years with risk conditions\nPCV13/15 recommendedPPSV23 \nRecommendedSingle PPSV23 revaccination \n5 yrsafter first dose\nChronic heart disease Y\nChronic lung disease Y\nDiabetes mellitus Y\nCerebrospinal fluid leak Y Y\nCochlear implant Y Y\nChronic renal failure or \nnephrotic syndromeY Y Y\nCongenital or acquired \nasplenia, or splenic \ndysfunctionY Y Y\nCongenital or acquired \nimmunodeficiencyY Y Y\nDiseases and conditions \ntreated with \nimmunosuppressive drugs or \nradiation therapyY Y Y\nHIV infection Y Y Y\nSickle cell disease or other \nhemoglobinopathiesY Y Y\nSolid organ transplant Y Y Y\nProposed risk-based pneumococcal vaccine recommendations for \nPCV unvaccinated children aged 6 –18 years with risk conditions\nPCV15/ 20recommended PPSV23 Recommended\nChronic heart disease Y Only if PCV15 used\nChronic kidney disease Y Only if PCV15 used\nChronic liver disease Y Only if PCV15 used\nChronic lung disease * Y Only if PCV15 used\nDiabetes mellitus Y Only if PCV15 used\nCerebrospinal fluid leak Y Only if PCV15 used\nCochlear implant Y Only if PCV15 used\nMaintenance dialysis or nephrotic syndrome Y Only if PCV15 used\nCongenital or acquired asplenia, or splenic \ndysfunctionY Only if PCV15 used\nCongenital or acquired immunodeficiency Y Only if PCV15 used\nDiseases and conditions treated with \nimmunosuppressive drugs or radiation \ntherapyY Only if PCV15 used\nHIV infection Y Only if PCV15 used\nSickle cell disease or other \nhemoglobinopathiesY Only if PCV15 used\nSolid organ transplant Y Only if PCV15 used\n*including moderate persistent or severe persistent asthma\nClinical Guidance\nPCV13 use for children aged <6 years\n•If only PCV13 is available when the child is scheduled to receive a PCV, \nPCV13 may be given as previously recommended.\n•If a child started the PCV series with PCV13, the child may complete the \nseries with PCV15 or PCV20 without giving additional doses. The PCV \nseries does not need to be restarted. \n64\nChildren aged 6 –18 years with a risk condition who \nhave received PCV13 only\nFor children who have previously received PCV13only, either adose of\nPCV20atleast 8weeks later orPPSV 23based onprevious dosing and\nschedules isrecommended .\n65\nChildren who have received hematopoietic stem cell \ntransplant (HSCT)\nChildren who received HSCT are recommended to receive three doses of PCV20 , 4 weeks \napart starting 3 –6 months after HSCT. A fourth PCV20 dose is recommended at least 6 \nmonths after the third PCV20 dose, or at least 12 months after HSCT, whichever is later. \nHSCT recipients who have started their pneumococcal vaccine series with PCV13 or PCV15 \nmay complete their 4 -dose pneumococcal vaccine series with PCV20 without giving extra \ndoses. \nIf PCV20 is not available, three doses of PCV15, followed by a dose of PPSV23 at least \n12 months after HSCT may be given. For patients with chronic graft -versus -host disease \nwho are receiving PCV15, a fourth dose of PCV15 can be given in place of PPSV23 since \nthese children are less likely to respond to PPSV23. \nA patient’s clinical team is best positioned to determine the appropriate timing of \nvaccination . \nLanguage aligned with clinical guidance for adults (October 2022 ACIP meeting)66\nAcknowledgements\n•ACIP and the Pneumococcal Vaccines Work Group\n•CDC contributors and consultants: Ryan Gierke, Jennifer Farrar, Kristin Andrejko, \nLindsay Zielinski, Emma Accorsi, Adam Cohen, Alison Albert, Angela Jiles, Noele \nNelson, Diepreye Ayabina, Andrew Leidner, Pedro Moro, Elizabeth Velazquez, \nMarc Fischer, Katie Hamilton, Noelle Sobotka, Rebecca Morgan, Doug Campos -\nOutcalt\n67\nSummary of voting language:\nNo change in PCV doses or schedule\n1. Use of either PCV15 or PCV20 is recommended for all children aged 2 –23 \nmonths according to currently recommended PCV dosing and schedules. \n2. For healthy children aged 24 –59 months or through age 71 months for children \nwith any underlying condition that increases the risk of pneumococcal disease \n(hereafter, risk condition)* with an incomplete PCV vaccination status , use of \neither PCV15 or PCV20 according to currently recommended PCV dosing and \nschedules isrecommended. \n*Risk conditions include: cerebrospinal fluid leak; chronic heart disease ; chronic kidney disease (excluding maintenance dialysis and nephrotic syndrome, which are included in \nimmunocompromising conditions); chronic liver disease; chronic lung disease (including moderate persistent or severe persiste nt asthma ); cochlear implant; diabetes mellitus; \nimmunocompromising conditions ( on maintenance dialysis or with nephrotic syndrome; congenital or acquired asplenia or splenic dysfunction; congenital or acquired \nimmunodeficiencies; diseases and conditions treated with immunosuppressive drugs or radiation therapy, including malignant ne oplasms, leukemias, lymphomas, Hodgkin disease, and \nsolid organ transplant; HIV infection; and sickle cell disease and other hemoglobinopathies).68\nSummary of voting language:\nModifications to schedule\n3. For children aged 2 –18 years with any risk condition who have received all \nrecommended doses before age 6 years\n•Using ≥1 dose of PCV20: No additional doses of any pneumococcal vaccine are \nindicated. This recommendation may be updated as additional data become available.  \n•Using PCV13 or PCV15 (no PCV20): A dose of PCV20 or PPSV23 using previously \nrecommended doses and schedule is recommended. \n4. For children aged 6 –18 years with any risk condition who have not received any dose \nof PCV13, PCV15, or PCV20, a single dose of PCV15 or PCV20 is recommended at least 8 \nweeks after the most recent dose of pneumococcal vaccination. When PCV15 is used, it \nshould be followed by a dose of PPSV23 at least 8 weeks later if not previously given. \n69\nSupplementary Slides\nGRADE Summary of Evidence\nSearch strategy: PCV20 use in children\nDatabase StrategyNo. \nidentifiedIncluded in \nGRADE\nClinicaltrials.gov Inclusion: Relevant Phase 2, or 3 randomized controlled trials of PCV20\n•Involved human subjects\n•Reported primary data\n•Included infants and children (age ≤18 years)\n•Included data relevant to the efficacy or effectiveness or immunogenicity and safety \noutcomes being measured\n•Included data for the dosage and timing being recommended:\no3+1 series for infants starting the vaccine series as currently recommended\noCatch -up vaccine schedule for older infants and children who did not start the 3+1 series \nin time\noUse of PCV20 to complete the PCV13 series\noUse of PCV20 in series with PPSV23 in older children with underlying conditions in series \nwith PPSV2312 3*\nPubmed\nMedline“PCV20” or “20 -valent pneumococcal conjugate vaccine” \nIncluded studies using the criteria listed above62 1\nAdditional \nresourcesUnpublished and other relevant data by consulting with the vaccine manufacturer\n2 3*\n*Same trials. Unpublished data from these trials were obtained from pharmaceutical companies. 71\nIncluded Studies: Routine PCV20 Use in Children Aged <2 years\nAuthor, yearStudy \ndesignIntervention Country Age Total \npopulationN \nInterventionN \ncomparisonOutcomesFunding \nsource\nSenders, \n2021Phase II RCT \nin healthy \nfull-term \ninfantsPCV20 @ 2, 4, 6, \nand 12 months of \nageUS42–98 \ndays of \nage at \nconsent460 232 228Immuno -\ngenicity and \nsafetyPfizer\nB7471011Phase III RCT \nin healthy \nfull-term \ninfantsPCV20 @ 2, 4, 6, \nand 12 –15 \nmonths of ageUS, \nPuerto \nRico42–98 \ndays of \nage at \nconsent1998 1001 997Immuno -\ngenicity and \nsafetyPfizer\nB7471013Phase III RCT \nin healthy \ninfantsPCV20 @ 2, 4, 6, \nand 12 –15 \nmonths of ageUS, \nPuerto \nRico, \nCanada, \nChile, \nArgentin\na, EU42–98 \ndays of \nage at \nconsent1511 1000 551 Safety Pfizer\nRCT=Randomized Controlled Trial72\nGRADE Summary of Findings: Routine PCV20 use in Children Aged <2 Years\nCertainty assessment № of patients Results\nCertainty Importance № of \nstudiesStudy \ndesignRisk of \nbiasInconsistency Indirectness ImprecisionOther \nconsiderationsIntervention comparisonRelative\n(95% CI)Absolute\n(95% CI)\nVaccine effectiveness\n21-2 RCTNot \nseriousNot serious SeriousaNot serious Not serious 921-1022 910-989•PCV20 had numerically lower \nimmune responses compared \nwith PCV13 for most of the 13 \nshared serotypes.\n•PCV20 did not meet one of the \nnoninferiority endpointsbfor \nsome serotypes (1, 3, 4, 9V, 23F, \nand 12F) after dose 3.\n•PCV20 noninferiorcto PCV13 for \nall 13 shared serotypes after \ndose 4. \n•PCV20 noninferiorcto PCV13 for \nall 7 additional serotypes after \ndose 4.Moderate Critical\nRCT=randomized clinical trial\na. These are all immunogenicity studies and there are no correlates of protection for some critical outcomes considered.\nb. Noninferiority for difference in percentages of participants meeting predefined IgG threshold value was defined as the low er bound of 2 -sided 95% confidence interval for percent difference (PCV20 -PCV13)> -10%. Additional 7 serotypes contained in \nPCV20 but not in PCV13 were compared with a PCV13 serotype with the lowest percentage excluding serotype 3. \nc. Noninferiority for GMC ratio was defined as the lower bound of 2 -sided 95% confidence interval of IgG GMC ratio (PCV20/PCV13) >0.5. Additional 7 serotypes contained in PCV20 but not in PCV13 were compared with a PCV13 serotype with the lowest \npercentage excluding serotype 3. \nReferences\n1. Senders S, Klein NP, Lamberth E, Thompson A, Drozd J, Trammel J, Peng Y, Giardina PC, Jansen KU, Gruber WC, Scott DA, Watson W. Safety and Immunogenicity of a 20 -valent Pneumococcal Conjugate Vaccine in Health y Infants in the United States. Pediatr Infect Dis J. 2021 Oct \n1;40(10):944 -951. doi: 10.1097/INF.0000000000003277.\n2.B7471011. A Phase 3, Randomized, double -blind trial to evaluate the safety and immunogenicity of a 20 -valent pneumococcal conj ugate vaccine in healthy infants73\nGRADE Summary of Findings: Routine PCV20 use in Children Aged <2 Years\nCertainty assessment № of patients Results\nCertainty Importance № of \nstudiesStudy \ndesignRisk of \nbiasInconsistency Indirectness ImprecisionOther \nconsiderationsIntervention ComparisonRelative\n(95% CI)Absolute\n(95% CI)\nSerious Adverse Events (SAEs) following vaccination\n21-3 RCT Not \nseriousNot serious Not serious Seriousa Not serious 101/2232\n(4.5%)64/1717\n(3.7%)No vaccine -related \nserious adverse events \nreportedModerate Critical\nRCT=randomized clinical trial\na. No vaccine -related serious adverse events reported\nReferences\n1.Senders S, Klein NP, Lamberth E, Thompson A, Drozd J, Trammel J, Peng Y, Giardina PC, Jansen KU, Gruber WC, Scott DA, Watson W. Safety and Immunogenicity of a 20 -valent Pneumococcal Conjugate \nVaccine in Healthy Infants in the United States. Pediatr Infect Dis J. 2021 Oct 1;40(10):944 -951. doi: 10.1097/INF.0000000000003277.\n2.B7471011. A Phase 3, Randomized, double -blind trial to evaluate the safety and immunogenicity of a 20 -valent pneumococcal conj ugate vaccine in healthy infants\n3.B7471013. A Phase 3, Randomized, double -blind trial to evaluate the safety of a 20 -valent pneumococcal conjugate vaccine in he althy infants. Data limited to U.S. and Puerto Rico sites. \n74\nIncluded Study: PCV20 Use in Children Aged 2 –18 Years with Underlying \nMedical Conditions\nAuthor, year Study design Intervention Country Age Total \npopulationN \nInterventionN \ncomparisonOutcomesFunding \nsource\nB7471014Phase III \nClinical Trial \nin healthy \nchildren, \nsome \npreviously \nvaccinatedSingle dose PCV20 \n@ 15m to <24m; \nprevious \nvaccination ≥3 \ndoses of PCV13\nUS15m \nto \n<24m209 209 N/A\nImmuno -\ngenicity\nand \nsafetyPfizerSingle dose PCV20 \n@ 2y to <5y; \nprevious \nvaccination ≥3 \ndoses of PCV132y to \n<5y216 216 N/A\nSingle dose PCV20 \n@ 5y to <10y5y to \n<10y201 201 N/A\nSingle dose PCV20 \n@ 10 to <18y10y \nto \n<18y205 205 N/A75\nGRADE Summary of Findings: PCV20 Use in Children Aged 2 –18 Years \nwith Underlying Medical Conditions\nCertainty assessment № of patients Results\nCertainty Importance № of \nstudiesStudy \ndesignRisk of \nbiasInconsistency Indirectness ImprecisionOther \nconsiderationsIntervention comparisonRelative\n(95% CI)Absolute\n(95% CI)\nVaccine effectiveness\n11 Non -RCTVery \nSerious\naNot \napplicableVery \nSeriousb,cNot \nseriousNot serious 752-757 NoneIgG GMCs were higher 1 -\nmonth post -PCV20 dose \ncompared to before \nvaccination for 13/13 shared \nserotypes and 7/7 additional \nserotypes, for all age groupsVery Low Critical\nRCT=randomized clinical trial\na. Study design is an open label non -randomized controlled trial with no comparator group. Downgraded for lack of randomization, la ck of blinding, and lack of a comparison group. \nb. Study population did not include children with underlying conditions\nc. This is an immunogenicity study and there are no correlates of protection for some critical outcomes considered\nReferences\nB7471014. Safety and Immunogenicity Study of 20vPnC in Healthy Children 15 Months Through 17 Years of Age76\nGRADE Summary of Findings: PCV20 use in Children Aged 2 –18  \nYears With Underlying Medical Conditions\nCertainty assessment № of patients Results\nCertainty Importance № of \nstudiesStudy designRisk of \nbiasInconsistency Indirectness ImprecisionOther \nconsiderationsPCV20 InterventionRelative\n(95% CI)Absolute\n(95% CI)\nSerious Adverse Events (SAEs) following vaccination\n11 Non -RCTSerious\naNot \napplicableSeriousb Seriousc Not serious5/831\n(0.6%) No vaccine -related \nSAEs reported Very Low Critical\nRCT=randomized clinical trial\na. Study design is an open label non -randomized controlled trial with no comparator group\nb. Study population did not include children with underlying conditions\nc. No vaccine -related serious adverse events reported; relative risk crossing 1  \nReference\nB7471014. Safety and Immunogenicity Study of 20vPnC in Healthy Children 15 Months Through 17 Years of Age\n77", "summary": "Evidence to Recommendations Framework and Policy Options:  Use of 20 -valent Pneumococcal Conjugate Vaccine in U.S. Children Miwako Kobayashi, MD, MPH Pneumococcal Vaccines Work Group Advisory Committee on Immunization Practices June 22, 2023National Center for Immunization & Respiratory Diseases PICO  QuestionShould PCV20 be recommended as an option for pneumococcal vaccination  for U.S. children? Population All U.S. children aged <2 yearsU.S. children aged 2 –18 years with  underlying…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/04-Pneumococcal-Kobayashi-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 77}
{"title": "01 Dengue Chen 508", "content": "Centers for Disease Control and Prevention\nNational Center for Emerging and Zoonotic Infectious Diseases\nACIP Dengue Vaccines Work Group\nWilbur Chen, MD, MSc\nACIP Member and Workgroup Chair\nAdvisory Committee on Immunization Practices\nACIP Meeting June 22, 2023\n\n▪DENV -1, 2, 3, 4\n•Lifelong DENV type -specific \nimmunity\n•Short -term cross -immunity (~1 –2 \nyears)\n•A second dengue infection is the \nmost important risk factor for  \nsevere dengue\n▪Dengue is the most common \nmosquito -borne virus globallyDengue Virus\nDengvaxia ™\nand previous \ndengue \ninfectionClinical trials found different outcomes after \nDengvaxia ™vaccination among children with and \nwithout previous dengue infection.\n•Children without previous dengue infection had a \nhigher risk for hospitalization and severe dengue if \nthey were vaccinated and then had a DENV infection.\n•Children with previous dengue infection were \nprotected from hospitalization and severe dengue if \nthey were vaccinated with Dengvaxia ™.\nDengvaxia ™ACIP Recommendation June 2021\nThree doses of Dengvaxia are indicated \nfor the prevention of dengue disease \ncaused by dengue virus serotypes 1, 2, \n3, and 4 in people 9 –16 years old with:\n•laboratory confirmation of previous \ndengue virus infection\nAND\n•living in endemic areas.\n\nPrevious Presentations to ACIP on TAK -003\nSep Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov2022 2023\n•\n••\n•Takeda dengue \nvaccine safety and \nefficacy presentation\nWorkgroup summary \nand interpretationDengue epidemiology\nReview of Sanofi dengue \nvaccine and ACIP \nrecommendation\nPresentations Today\nIntroduction of policy questions for TAK -003\n•Dr. Alfonso Hernandez, CDC, NCEZID, DVBD\nCost effectiveness analysis and health impacts of routine vaccination \nwith TAK -003 dengue vaccine in Puerto Rico\n•Dr. Guido España , Notre Dame\nSummary of two economic models for dengue vaccine TAK -003 use in \nPuerto Rico​\n•Dr. RajReni Kaul, CDC\nPartial evidence to recommendations framework for TAK -003\n•Dr. Joshua Wong, CDC, NCEZID, DVBD\nFuture Presentations to ACIP on TAK -003\n*Timeline subject to changeSep Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov2022 2023\n•\n••\n•\n•\n••\n••\n•\n•Takeda dengue \nvaccine safety and \nefficacy presentation\nWorkgroup summary \nand interpretationPolicy questions\nCost-effective (CE) analysis \n(CDC/Notre Dame)\nComparison of CE models\nPartial EtRDengue epidemiology\nReview of Sanofi dengue\nvaccine and ACIP \nrecommendation Full EtR*\nDraft recommendation*\nVote*\nACIP Dengue Vaccines Work Group\nACIP Members\n•Wilbur Chen (Chair)\n•Kathy Poehling\n•Beth Bell\n•Veronica McNally\nCDC Co -Leads\n•Gabriela Paz -Bailey\n•Laura Adams\nEx Officio Members\n•Kaitlyn Morabito (NIH)\n•Ralph LeBlanc (FDA)\n•Ihid Carneiro Leao (FDA)\n•Kirk Prutzman (FDA)•Srihari Seshadri (DOD)\n•Liaison Representatives\n•Elizabeth Barnett (AAP)\n•Rob Schechter (AIM)\nConsultants\n•Edwin Asturias\n•Robert Atmar\n•Alan Barrett\n•IrisCardona\n•Anna Durbin\n•Tony Marfin\n•Kristen Pierce\n•Anita ShetCDC Contributors\n•Joshua Wong\n•Nicole Medina\n•Mimi Eckert\n•Rachel Eidex\n•Alfonso Hernandez\n•Susan Hills\n•Terri Hyde\n•Mike McNeil\n•Jorge Munoz\n•Erin Staples\n•Cindy Weinbaum\n•Rita Helfand", "summary": "Centers for Disease Control and Prevention National Center for Emerging and Zoonotic Infectious Diseases ACIP Dengue Vaccines Work Group Wilbur Chen, MD, MSc ACIP Member and Workgroup Chair Advisory Committee on Immunization Practices ACIP Meeting June 22, 2023  ▪DENV -1, 2, 3, 4 •Lifelong DENV type -specific  immunity •Short -term cross -immunity (~1 –2  years) •A second dengue infection is the  most important risk factor for   severe dengue ▪Dengue is the most common  mosquito -borne virus…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/01-Dengue-Chen-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 8}
{"title": "02 Dengue Hernandez 508", "content": "Centers for Disease Control and Prevention\nNational Center for Emerging and Zoonotic Infectious Diseases\nIntroduction of Policy Questions for TAK -003\nAlfonso Hernandez -Romieu, MD, MPH\nACIP June 22, 2023\nDengue Branch, CDC\n\nWe formulated PICO questions based on the \ndirectness of data and risk -benefit differences.\n*Persons aged 17 years were considered in this category but were not included in original immunobridging (18 –60 years) or    \nphase 3 trials (4 –16 years)•4–16 years: 57-month vaccine efficacy from a phase 3 \nrandomized controlled trial\n•17*–60 years: Non -inferiority of antibody titer ratios post -\nvaccination (2 doses) compared to persons aged 4 –16 years \n(i.e., immunobridging )\nResult: Developed PICO questions by age -group\nWe formulated PICO questions based on the \ndirectness of data and risk-benefit differences .\n•No efficacy against hospitalizations for DENV -3 among \nseronegative vaccine recipients compared to placebo (-87.9%; \n95% CI: -573.4, 47.6%).​\n•Data insufficient to rule out an increased risk among \nseronegative vaccine recipients.\nResult: Developed PICO questions by serostatus\nHospitalization for DENV -3 and DENV -4 among \nseronegative* children was low.\nPlacebo\nn=1832Incidence\ndensity/100\nperson -yearsTAK-003\nn=3714Incidence\ndensity/100\nperson -yearsVE (95% CI)\nDENV -1 14 0.17 6 0.03 78.4% (43.9, 91.7%)\nDENV -2 23 0.28 0 0.0 100% (NE, NE)\nDENV -3 3 0.04 11 0.07–87.9% (–573.4, 47.6%)\nDENV -4 1 0.01 0 0.0 100% (NE, NE)\n*Seronegative refers to no serologic evidence of previous dengue infection before vaccination.\nWe formulated PICO questions based on the \ndirectness of data and risk-benefit differences .\n•No efficacy against hospitalizations for DENV -3 among \nseronegative vaccine recipients compared to placebo (-87.9%; \n95% CI: -573.4, 47.6%).​\n•Data insufficient to rule out an increased risk among \nseronegative vaccine recipients.\nResult: Developed PICO questions by serostatus\nPICO questions include persons living in \ndengue endemic areas only.\n•Recommendations for travelers to dengue endemic areas will be \naddressed by the work group after the October 2023 ACIP meeting.\n•Travelers to endemic areas will require a separate evidence -to-\nRecommendations ( EtR) framework including but not limited to:\n•public health importance\n•benefits and harms\n•resource use\nPICO Questions\n1.Should two doses of TAK -003 be administered routinely to seropositive* \npersons aged 4 –16 years living in dengue -endemic areas?\n2.Should two doses of TAK -003 be administered routinely to seronegative \npersons aged 4 –16 years living in dengue -endemic areas?\n3.Should two doses of TAK -003 be administered routinely to seropositive* \npersons aged 17 –60 years living in dengue -endemic areas?\n4.Should two doses of TAK -003 be administered routinely to seronegative \npersons aged 17 –60 years living in dengue -endemic areas?\n*Recommendation for seropositive individuals only will require prevaccination screening for previous dengue virus infection.\nSeropositive Seronegative\n4–16 years\nChildren/Adolescents•Vaccine Efficacy (VE)\n•Safety\n•Cost -effectiveness (CE)•VE\n•Safety\n•CE\n17–60 years\nAdults•Immunobridging *\n•Safety\n•CE•Immunobridging\n•Safety\n•CEData elements used for each policy question\n*Immunogenicity in seropositive adults inferred from data in seronegative adults.", "summary": "Centers for Disease Control and Prevention National Center for Emerging and Zoonotic Infectious Diseases Introduction of Policy Questions for TAK -003 Alfonso Hernandez -Romieu, MD, MPH ACIP June 22, 2023 Dengue Branch, CDC  We formulated PICO questions based on the  directness of data and risk -benefit differences. *Persons aged 17 years were considered in this category but were not included in original immunobridging (18 –60 years) or     phase 3 trials (4 –16 years)•4–16 years: 57-month…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/02-Dengue-Hernandez-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 8}
{"title": "03 Dengue Espana 508", "content": "Economic analysis and health impacts of routine vaccination\nwith TAK- 003 dengue vaccine inSan Juan, Puerto Rico\nGuido España, Manar Alkuzweny ,Alex Perkins\nUniversity ofNotre Dame\nJune 22nd,2023\nConflicts ofinterest & Disclosures\n•GEand APhave previously received research funding from \nGlaxoSmithKline tosupport unrelated research ondengue vaccine\ndevelopment.\n•APcurrently receives research funding and consulting fees from\nEmergent Biosciences tosupport unrelated research on \nchikungunya vaccine development.\n•As of June 2023, GE is an employee of CDC. This work was \nperformed while working at the University of Notre Dame. The \nfindings and conclusions in this presentation are those of the \nauthor(s) and do not necessarily represent the views of the CDC.\n2\nAbbreviation Full term/Meaning\nVCD Virologically confirmed disease\nVE Vaccine efficacy\nDENV (e.g., DENV -3) Dengue virus (e.g., serotype 3 dengue virus)\nHPV Human papillomavirus\nPICO Policy question articulated as Population, Intervention, \nComparison, Outcomes\nAdditional hospitalizations Hospitalization induced by vaccine -enhanced disease\nICER Incremental cost -effectiveness ratio ($/QALY , $/hospitalization \naverted)\nQALY Quality adjusted life years\n3Terminology\nWe modeled six scenarios to answer each of the \npolicy (PICO) questions. \n•Age group scenarios: \n•4 –16 years \n•17 –60 years\n•4 –60 years\n•For each age group we modeled:\n•Without required pre -vaccination screening (vaccinate \nseropositives and seronegatives )\n•With required pre -vaccination screening (vaccinate \nseropositives only)\n4\nOutcomes of interest included benefits, harms, and \ncosts. \n•Epidemiological outcomes: \n•VCD* and hospitalizations averted \n•Dengue hospitalizations among vaccinated seronegative \npersons infected with DENV -3 and DENV -4.\n•Health Outcomes:\n•QALYs gained \n•Economic outcomes:\n•ICER ($/QALY)\n•ICER ($/hospitalization averted)\n*VCD refers to medically attended cases only 5\nWe calibrated an agent -based model to reproduce patterns \nofserotype circulation, force of infection, and age-specific \nincidence.\n•Wecreated asynthetic population torepresent demographic and\ngeographic characteristics ofSan Juan, Puerto Rico.\n•Our model simulates individual daily activities ofhumans and \nmosquitoes.\n•Model calibrated using 30years ofhistorical dengue surveillance data \nto reproduce observed force of infection and age -specific \nincidence.\n6\nThe serotype distribution simulated over 10 year time horizon of vaccination \nwas modeled on 30 (1986-2016) years of data from San Juan, Puerto Rico.\n*Model based on 1,000 bootstraps with different proportion of serotypes in every simulation. Average reflects the mean propor tion of serotypes among \nentire model. These estimates are preliminary and are subject to change.SerotypeAverage proportion in \nmodel*\n• DENV -1 14% (5% -25%)\n• DENV -2 35% (17% -51%)\n• DENV -3 29% (11% –46%)\n• DENV -4 22% (9% -40%)\n7\nThe estimated seroprevalence among persons 9 years of \nage was approximately 40%. \n•30% ofindividuals aged 5–9years were seropositive .\n•People aged 20, 75% of people had ≥1 infection bytheend ofthe\ncalibration.Age group\n8\nWesimulated the vaccine roll-out based onprevious \nintroduction ofHPV vaccine in the US*.\n•Vaccine coverage increased gradually from 0% to ~40% in 10 years \nand was distributed evenly across age ranges in the scenario.\n•Wesimulated additional scenarios of2xand 0.5x thefinal coverage.\n*https://www.cdc.gov/nchs/data/hus/2020 -2021/VaxTn.pdf 9\nVaccine efficacy and vaccine protection assumptions\n10\nModel and trial estimates of vaccine efficacy for VCD and \nhospitalization among seropositive participants .\n54100\n70 686796\n74100\n020406080100\n1 2 3 46385\n43605680\n5271\n020406080100\n1 2 3 4VCD HospitalizationVaccine efficacy\nTakeda –ACIP WG presentation September13th –100% VE values are assumed. Biswal (Takeda). ACIP, February 17, 2023.11\nModel and trial estimates of vaccine efficacy for VCD and \nhospitalization among seronegative participants .\nVCD Hospitalization\n3096\n30\n-14588\n-16\n-106\n-150-100-50050100\n1 2 3 48599\n-303978100\n-88100\n-150-100-50050100\n1 2 3 4Vaccine efficacy\n12\nTakeda –ACIP WG presentation September 13th–100% VE values are assumed. Biswal (Takeda). ACIP, February 17, 2023.\nVaccine protection assumptions \n•Protection varies foreach serotype (DENV 1 -4)and serostatus (seronegative\norseropositive).\n•The duration of protection was estimated as\n•VCD for seronegatives (13.1yrs) and for seropositives (17.4yrs)\n•Hospitalization for seronegatives (19.3) and for seropositives (25.6).\n•Equal level of protection against infection and disease given infection. \n•In scenarios with pre -vaccination screening, the coverage of pre -vaccination \nscreening is the same as the vaccine rollout coverage (without screening). The \ntest has 80% sensitivity and 98% specificity for detecting previous dengue \ninfection.\n•Wesimulated outcomes of VCD and hospitalizations over 10years in \nscenarios with vaccination compared to scenarios without vaccination.\n•We assumed that all individuals testing positive are vaccinated.\n14\nEpidemiological outcomes*: VCD and hospitalizations \naverted (Benefits)\n15*Results are preliminary and are subject to change.\nNo pre -vaccination screening increased the proportion \nof total VCD averted compared to screening . \n02468101214161820\n1 2 3% of symptomatic VCD averted in the total \npopulation\n389\n167\n16*Results are preliminary and are subject to change.\nNo pre -vaccination screening increased the proportion of \ntotal hospitalizations averted compared to screening . \n02468101214161820\n1 2 3% ofhospitalizations averted in the total \npopulation\n3 31315\n1012\n17*Results are preliminary and are subject to change.\nEpidemiological outcomes: Additional hospitalizations \n(Harms)\n18\nOutcomes: Additional hospitalizations (Harms)\n•We used the ratio of averted hospitalizations to additional \nhospitalizations as a relative measure of harm. \n•Additional hospitalizations only occurred among seronegative persons \nwho received the vaccine and were infected with DENV -3 or DENV -4 \npost -vaccination.\n19\nScreening increased the ratio of averted to additional \nhospitalizations compared to no pre-vaccination screening .\n0102030405060708090100\n1 2 3Ratio ofhospitalizations averted to\nadditional hospitalizations*\n6:115:135:1\n18:1102:1\n69:1\n*among seronegative persons who received the vaccine and were infected with DENV -3 post -vaccination.    Note: Results are prelim inary and are subject to change.\n20\nEconomic outcomes*\n21\nWeestimated theIncremental Cost -Effectiveness\nRatio to determine cost -effectiveness\n•Weestimated thequality -adjusted life-years (QALYs) gained with\nroutine vaccination using disability weights (Zeng et al. 2018)\n•The unit cost perfully vaccinated individual was varied from 100\nto 600 USD (330 USD baseline).Costintervention–Costnointervention= ICER\nQALYintervention–QALYnointervention\n*The cost per fully vaccinated individual was estimated as 150 USD per dose with an additional 15 USD for vaccine administrat ioncosts per dose. All \ncosts were estimated for the year 2022.\n22\nEconomic outcomes* by scenario for a public \npayer perspective, over 10 years, 3% discounting.\nAge \ngroupPre-vaccination \nscreeningQALYs \ngainedICER $ / QALY \ngainedICER $ / \nhospitalization \naverted\n4-16 Yes 17 181,918 16,800\n4-16 No 35 254,751 46,813\n17-60 Yes 89 396,574 48,986\n17-60 No 118 314,597 39,886\n4-60 Yes 106 384,830 48,305\n4-60 No 134 326,412 45,495\n23*Results are preliminary and are subject to change.\nSummary\n•Our model simulations show some benefits from vaccination in terms of\nsymptomatic cases and hospitalizations averted.\n•These benefits depend ontheserostatus ofthevaccinees and the\ncirculating serotypes.\n•Overall, pre-vaccination screening reduces thepotential negative\noutcomes inseronegative individuals.\n•ICERs per QALY gained and ICER per hospitalization averted were higher \nwhen implementing pre -vaccination screening except in the 4 –16 age \ngroup where screening was more cost -effective.\n•Cost -effectiveness of the intervention depended on the \nseroprevalence, which is lower for younger age groups.\n24\nLimitations\n•Our model projections are not predictions on the serotype circulation or \ntheburden of disease.\n•Our results on the benefits and cost -effectiveness of the intervention \ndepend on the circulation of specific serotypes during the projection \nperiod.\n•We are not including QALYs loss due to death in the cost -effectiveness \nanalysis.\n24\nAcknowledgements\nThis analysis isbased onprevious analyses described inthe \nmanuscript byEspaña etal.:“Model -based assessment ofpublic \nhealth impact and cost-effectiveness ofdengue vaccination\nfollowing screening for prior exposure. PLOS NTDs 2019” (España \netal.,2019). The manuscript was prepared incollaboration with \nother authors: Yutong Yao, Kathryn B.Anderson, Meagan C. \nFitzpatrick, David L.Smith, Amy C.Morrison, Annelies\nWilder-Smith, and Thomas W.Scott.\nReferences I\nZeng, W.,Halasa -Rappel, Y.A.,Durand, L.,Coudeville, L.,& \nShepard, D.S.(2018). Impact ofanonfatal dengue episode \nondisability -adjusted lifeyears: Asystematic analysis. The \nAmerican Journal ofTropical Medicine and Hygiene ,99(6), \n1458 –1465. https://doi.org/10.4269/ajtmh.18 -0309\nHalasa ,Y.A.,Shepard, D.S.,&Zeng, W.(2012). Economic cost of\ndengue inPuerto Rico. The American journal oftropical \nmedicine and hygiene ,86(5),745–752.\nEspaña ,G.,Yao, Y.,Anderson, K.B.,Fitzpatrick, M.C., Smith, D.\nL.,Morrison, A.C.,Wilder -Smith, A.,Scott, T.W.,&\nPerkins, T.A.(2019). Model -based assessment ofpublic\nhealth impact and cost-effectiveness of dengue vaccination\nfollowing screening forprior exposure. PLOS Neglected\nTropical Diseases ,13(7),1–21. \nhttps://doi.org/10.1371/journal.pntd.0007482", "summary": "Economic analysis and health impacts of routine vaccination with TAK- 003 dengue vaccine inSan Juan, Puerto Rico Guido España, Manar Alkuzweny ,Alex Perkins University ofNotre Dame June 22nd,2023 Conflicts ofinterest & Disclosures •GEand APhave previously received research funding from  GlaxoSmithKline tosupport unrelated research ondengue vaccine development. •APcurrently receives research funding and consulting fees from Emergent Biosciences tosupport unrelated research on  chikungunya…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-21-23-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-06-21-23/03-Dengue-Espana-508.pdf", "doc_date": "2023-06-21", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 26}
{"title": "01 Chikungunya Chen 508", "content": "CHIKUNGUNYA VACCINES\nACIP Meeting\nJune 26, 2024\nWilbur Chen, MD, MS\nChair, ACIP Chikungunya Vaccines Work Group\n•Chikungunya Vaccines Work Group formed in May 2022 \n•Developing policy options for ACIP’s consideration for use of chikungunya \nvaccine among U.S. persons at risk of chikungunya \n-Travelers\n-Laboratory workers\n-Residents of U.S. territories and states with risk of transmissionBackground\n•October 2022\n-Overview of chikungunya virus disease and vaccines\n-Overview of live attenuated chikungunya vaccine\n•February 2023\n-Epidemiology of chikungunya globally and among U.S. travelers\n-Sequelae of chikungunya\n•June 2023\n-Value of a vaccine to U.S. travelers\n-Chikungunya virus infection among laboratory workers\n•October 2023\n-EtR for use of live attenuated chikungunya vaccine among U.S. travelers and \nlaboratory workersRecap of previous Work Group presentations to ACIP (1)\n•February 2024\n-Recommendations approved for use of live attenuated chikungunya vaccine \namong U.S. travelers and laboratory workersRecap of previous Work Group presentations to ACIP (2)\n•Update on chikungunya vaccines \n•Epidemiology of chikungunya in U.S. territories and states\n•Cost- effectiveness of use of live attenuated chikungunya vaccine among \nadults living in U.S. territories \n•Next steps for Work GroupOverview of today’s session\nChikungunya Vaccines Work Group members\nACIP ACIP Liaisons Invited Consultants ( cont )\nWilbur Chen, Univ Maryland Elizabeth Barnett, ISTM Margaret Ryan, DoD\nMatthew Daley, Kaiser Permanente James Campbell, AAP Steven Schofield, CATMAT\nMary Pat Friedlander, AAFP David Shlim, Jackson Hole Travel & Trop Med\nCDC Lead Saroj Rai, AIM Nestor Sosa, Uni New Mexico Hospital\nSusan Hills, DVBD Sanet Torres, San Jorge Children & Women's Hospital\nInvited Consultants Kirsten Vannice, Bill & Melinda Gates Foundation\nEx Officio Alan Barrett, Univ Texas Galveston Mary Wilson, Univ California San Francisco\nRobin Levis, FDA Beth Bell, Univ Washington\nSixun Yang, FDA Carina Blackmore, Florida Dept Health\nLesley Dupuy (NIH) Alan Lam, DoD\nChikungunya Vaccines Work Group CDC participants\nDVBD DGMH ISD\nErin Staples Kevin O’Laughlin Elisabeth Velazque z\nSarah Guagliardo\nAnn Powers DHQP GRADE/ETR consultants\nLaura Adams Michael McNeil Doug Campos -Outcalt\nJoshua Wong Rebecca Morgan\nGID\nNCEZID Rebecca Casey ACIP Secretariat\nRita Helfand Jessica MacNeil, NCIRD\nLeslie Lee, NCIRD", "summary": "CHIKUNGUNYA VACCINES ACIP Meeting June 26, 2024 Wilbur Chen, MD, MS Chair, ACIP Chikungunya Vaccines Work Group •Chikungunya Vaccines Work Group formed in May 2022  •Developing policy options for ACIP’s consideration for use of chikungunya  vaccine among U.S. persons at risk of chikungunya  -Travelers -Laboratory workers -Residents of U.S. territories and states with risk of transmissionBackground •October 2022 -Overview of chikungunya virus disease and vaccines -Overview of live attenuated…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/01-Chikungunya-Chen-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 7}
{"title": "02 Chikungunya Hills 508", "content": "Update on chikungunya vaccinesNational Center for Emerging and Zoonotic Infectious Diseases\nSusan Hills MBBS MTH\nCDC Lead , Chikungunya Vaccines Work Group\nArboviral Diseases Branch\nDivision of Vector -Borne Diseases\nFort Collins, Colorado\nACIP Meeting, June 26, 2024\n•Manufactured by Bavarian Nordic\n•Submission of BLA to FDA completed on June 17, 2024\n•Licensure possible first half of 2025\n•Intended age group is adolescents and adults aged ≥12 years\n•Single dose schedule Virus -like particle chikungunya vaccine\n•Manufactured by Valneva as IXCHIQ\n•Licensed November 9, 2023\n•Age group currently adults ≥18 years\n•Single dose schedule Live attenuated chikungunya vaccine", "summary": "Update on chikungunya vaccinesNational Center for Emerging and Zoonotic Infectious Diseases Susan Hills MBBS MTH CDC Lead , Chikungunya Vaccines Work Group Arboviral Diseases Branch Division of Vector -Borne Diseases Fort Collins, Colorado ACIP Meeting, June 26, 2024 •Manufactured by Bavarian Nordic •Submission of BLA to FDA completed on June 17, 2024 •Licensure possible first half of 2025 •Intended age group is adolescents and adults aged ≥12 years •Single dose schedule Virus -like particle…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/02-Chikungunya-Hills-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 3}
{"title": "03 Chikungunya Hills 508", "content": "Chikungunya epidemiology in U.S. territories and \nstates with risk of transmissionNational Center for Emerging and Zoonotic Infectious Diseases\nSusan Hills MBBS MTH\nCDC Lead , Chikungunya Vaccines Work Group\nArboviral Diseases Branch\nDivision of Vector- Borne Diseases\nFort Collins, Colorado\nACIP Meeting, June 26, 2024\n•Mosquito -borne disease\n•Key vectors are Aedes aegypti \nand Aedes albopictus mosquitoesChikungunya \n\n•Typically tropical and subtropical \nregions\n•Periodically causes large outbreaks \n-Often high attack rates\n•Virus transmission usually highest \nduring wet seasonDistribution and disease burden in endemic areas\nCountries and territories with current or past \ntransmission of chikungunya virus\n\n•Febrile illness with typically severe \na\nrthralgia, can be debilitating\n•Other symptoms include headache, \nr\nash, myalgia, anorexia \n•No anti - viral treatment availableClinical features of acute chikungunya virus infection\n\n•Rare serious complications (e.g., \nmyocarditis, hepatitis, neurologic illness)\n•Deaths rare and reported mostly in\n-Older adults, particularly those with comorbidities\n-Young infants infected perinatally or by mosquito bitesComplications of chikungunya\nImages from : https://www.paho.org/en/topics/chikungunya\n•Acute symptoms usually resolve in 7 –10 days\n•Some patients have continuation or relapse \nof symptoms\n•Ongoing arthralgia of variable severity possibly present in up to ~50% at 3 months and ~30% at 12 monthsChronic arthralgia following chikungunya\n\nPuerto Rico\n•Largest U.S territory \n-Po pulation ~3.2 million persons\n-Area ~3,500 miles2  \n•Tropical climate\n•Aedes aegypti pr esent \n•Dengue endemic Puerto Rico\n\n•Data from passive and sentinel surveillance systems\n•No single data source provides accurate and complete information \n•Surveillance activities, reporting practices, and laboratory testing \napproaches changed during outbreak\n-When laboratory capacity exceeded, testing prioritized for certain groups\n-When number of suspected cases reached thousands per week, limitation on \ntypes of cases to be reported \n•Key points\n-Numbers of cases often substantial underestimate of true cases\n-Data provide reasonable representation of actual disease epidemiologyData sources \n•Confirmed cases : detection of nucleic acid by RT -PCR\n•Probable cases : IgM antibodies in serum or cerebrospinal fluid\n•Chikungunya IgM antibodies can persist after acute infection\n•13–18 months: 56% with IgM1\n•2–3 years: 11% with IgM2 Laboratory criteria for chikungunya cases\n1. Grivard  et al, Path Biol 2007;    2. Costa et al, Rev Soc Bras Med Trop 2021 \n•Chikungunya emerged in 2013\n-First case reported in Saint Martin island in December \n•Rapid increase in countries and territories reporting transmission\n•In Puerto Rico, first laboratory -confirmed case in May 2014Chikungunya emergence in the Caribbean\nChikungunya cases reported by year and case status, \nPuerto Rico, 2014 –2020\n0200040006000800010000\n2014 2015 2016 2017 2018 2019 2020Probable\nConfirmed\nChikungunya cases reported by year and case status, \nPuerto Rico, 2014 –2020\n0200040006000800010000\n2014 2015 2016 2017 2018 2019 2020Probable\nConfirmed\nLast laboratory -confirmed \nsymptomatic clinical case\nChikungunya cases by month of illness onset during \ntwo main outbreak years, 2014 –2015\n050010001500200025003000\nJan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec\n2015 2014\nChikungunya cases by sex, Puerto Rico, 2014 –2020 \n(N=10,293)* \nSex No. (%)\nFemale 5,116 (52%)\nMale 4,708 (48%)\n*n=469 with unknown sex\nChikungunya cases by age group, Puerto Rico, 2014 –\n2020 (N=10,293)*\nYears No. (%)\n0–19 4,328 (42%)\n20–39 2,055 (20%)\n40–59 1,931 (19%)\n≥60 1,865 (18%)\n*n=114 with unknown age\nChikungunya cases by municipality, Puerto Rico, \n2014 –2020\n\n•Household cluster survey among persons aged 1– 50 years in one \nmunicipality in southern Puerto Rico in 2018– 2019\n-31% seroprevalence1\n•Samples from blood donors aged ≥16 years collected in March 20152\n-23% seroprevalence2 \n•Based on 30% seroprevalence rate, ~ 1 million persons estimated to have \nbeen infected  during outbreak \n-~650,000 –85 0,000 clinical cases Proportion of Puerto Rico population infected\n1. 1,268 of 4,035 participants (Adams LE at al, PLoS  NTD 2022);     2. 242 of 1,031 samples (Simmons G et al, Emerg  Infect Dis 2016)\nUnited States Virgin Islands (USVI)\n•First locally acquired case detected in \nearly June 20141 \n•Initial transmission on Saint ThomasInitial transmission of chikungunya in USVI\nSource: https://ontheworldmap.com/virgin -islands- us/\n1. Feldstein LR et al, Am J Trop Med Hyg 2016  \nEpidemic curve of chikungunya cases* by island, USVI, \n2014 –2015 (N=637)\n*Confirmed or probable Feldstein LR et al, Am J Trop Med Hyg  2016 \nLast laboratory -\npositive case \nFebruary 2015\n•31% persons had evidence of past infection in seroprevalence survey \napproximately 1 -year post -outbreak1\n•~33,000 persons estimated to have been infected during outbreak \n-~21,000– 28,000 clinical cases during 8- month  outbreak periodProportion of USVI population infected, 2014 –2015\n1. Hennessey MJ e al, Am J Trop Med Hyg 2018                    *Laboratory confirmed or probable\nOther U.S. territories and freely associated states\n•American Samoa1\n-Outbreak began June 2014 \n-Unconfirmed information suggested ≥823 suspected cases\n-Unclear duration but no evidence of transmission by end of 2015\n•Guam and Commonwealth of the Northern Mariana Islands (CNMI)\n-No cases reportedOther U.S. territories\n1. Roth A et al, Eurosurveillance 2014; ArboNET  data \n•Federated States of Micronesia (Yap State)1\n-Outbreak from Aug 2013 –Aug 2014 with peak Oct –Dec 2013\n-1,761 suspected cases reported \n-Attack rate of 155 clinical cases per 1,000 population, so ~15% population sought \ncare for suspected illness\n•Marshall Islands2\n-Outbreak began February 2015\n-Unclear duration and extent but unconfirmed information suggests >1,000 \nsuspected cases\n•Palau\n-No cases reportedFreely associated states\n1. Pastula DM et al, PLoS  NTD 2017; 2. Ministry of Health Republic of the Marshall Islands Chikungunya Report, April 2015. \n•3 territories and 2 affiliated states have had chikungunya outbreaks\n•Outbreaks were explosive \n•For Puerto Rico and USVI, ~30% of population was likely infected, with \n20% –25% of the population having clinical illness mainly during a period ~6 \nmonths\n•All outbreaks began 2013– 2015 \n•No evidence of confirmed transmission since 2017 (Puerto Rico) or earlier \nin islands with smaller populations \n•Timing of future transmission or outbreaks and likely pattern unknown Summary: \nChikungunya in U.S territories and affiliated states \nLocally -acquired cases in U.S states\nAedes aegypti           Aedes albopictus  Estimated potential range of Aedes aegypti and Aedes \nalbopictus in the United States, 2017\nhttps://www.cdc.gov/mosquitoes/php/toolkit/potential -range -of-aedes.html\n•First local transmission of chikungunya virus in \nc\nontinental United States was in 2014\n•Occurred in context of chikungunya outbreak in \nAme\nricas and increase in traveler cases\n•After 1st locally -acquired case in June, 11 additional \ncases identified in 4 counties in southern Florida\n•Two patients lived within 1,500 feet of each other and \no\nther cases were sporadic reportsFlorida (N=12)*#\n*11 cases described in MMWR and one case reported after MMWR published\n#Does not include one case from different area of Florida published by clinician in 2021 (Am J Emerg  \nMed, 2021) as IgM positive result not confirmed when tested by neutralizing antibody testing\nKendrick K, et al. MMWR 2014;63(48):1137\nTexas (N=1)\n•One case in Cameron County\n•Occurred in November 2015 \nMexico\nLocation of Cameron County, Texas\nFor more information, contact CDC\n1-800- CDC- INFO (232 -4636)\nTTY:  1 -888- 232- 6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.\nAcknowledgments \n•Puerto R ico Department of Health\n•Nicole Lindsey, Arboviral Diseases Branch\n•Laura Adams, Dengue Branch\n•Joshua Wong, Dengue Branch", "summary": "Chikungunya epidemiology in U.S. territories and  states with risk of transmissionNational Center for Emerging and Zoonotic Infectious Diseases Susan Hills MBBS MTH CDC Lead , Chikungunya Vaccines Work Group Arboviral Diseases Branch Division of Vector- Borne Diseases Fort Collins, Colorado ACIP Meeting, June 26, 2024 •Mosquito -borne disease •Key vectors are Aedes aegypti  and Aedes albopictus mosquitoesChikungunya   •Typically tropical and subtropical  regions •Periodically causes large…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/03-Chikungunya-Hills-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 31}
{"title": "04 Chikungunya Kilburn 508", "content": "1\nCost -effectiveness of live attenuated chikungunya vaccine among adults \nliving in US territories\nKelly Kilburn, PhD, Martin I. Meltzer, PhD, Seonghye Jeon, PhD, Susan L. Hills, MBBS, \nMTH, Bishwa B. Adhikari, PhD, Nicole P. Lindsey, MS, J. Erin Staples, MD, PhD\nJune 27th, 2024\nNational Center for Emerging Zoonotic and Infectious DiseasesNational Center for Emerging Zoonotic and Infectious Diseases\n\n2•Authors have no known conflict of interests\n•The findings and conclusions in this presentation are those of the authors and do \nnot necessarily represent the views of the Centers for Disease Control and Prevention.Conflicts of Interest Statement\n3•Research question\n•Methods \n•Results\n•Sensitivity analyses\n•Limitations\n•SummaryOutline \n4•What is the cost -e ffectiveness of using a single dose of the live \nattenuated chikungunya vaccine among the population aged ≥18 years \nin US territories* that previously experienced an outbreak of chikungunya?\n*American Samoa, Puerto Rico (PR), and US Virgin Islands (USVI)Research Question\n5Methods\n6•Population- based model\n-Entire population of three US territories in model \n•Time step: 1 year\n•Analytic time horizon: 30 years starting in 2024\n•Discount rate: 3%\n•Perspectives: societal and healthcare payer\n•One chikungunya outbreak occurring in 2034Economic Model\n7•Use of live-attenuated chikungunya vaccine\nStrategy 1: \nRoutine VaccinationStrategy 2: \nOutbreak Vaccination\nAnnual Vaccination Yes No\nCoverage rate1 20% --\nOutbreak campaign in 2034 Yes Yes\nCoverage rate2 70%3 70%\n1 Routine coverage rate range based on annual influenza vaccine uptake in Puerto Rico (CDC data)\n2 Outbreak coverage rate range based on Covid -19 vaccine uptake in Puerto Rico (CDC data)\n3 Total coverage rate for outbreak year considers routine vaccinations from all prior years and vaccinations during outbreak. Individuals are vaccinated only once.Intervention\n8Routine strategy\nInitial vaccination\nof target populationOutbreak vaccinationof target population\nVaccination of new 18 yo Vaccination of new 18 yo\nOutbreak strategy\nOutbreak vaccinationof target population2053\n20532024\n2024 20342034Strategy Comparison\n9•Estimated population- level health outcomes\n-Symptomatic cases\n-Hospitalizations\n-Chronic joint pain cases\n-Deaths\n-Quality -adjusted life -years (QALYs) lost \n•Estimated economic outcomes\n-Societal costs – vaccination, medical, and lost productivity costs\n-Healthcare payer costs – vaccination and medical costsOutcomes\n10•Calculated incremental cost -effectiveness ratios comparing \nvaccination to no vaccination \n-Measured as $ per each outcome averted (or QALYs gained)\n•Monte Carlo simulation with 1,000 replications to estimate results \nwith 95% CIs using @Risk software\n•Conducted sensitivity analyses (univariate and scenario)Analysis Approach\n11Model Assumptions\n12•Chikungunya virus infection confers lifetime immunity\n•Outbreak would stop once certain level of population is infected \n(halting seroprevalence)Lifelong Immunity and Halting Seroprevalence\n\n13Model Inputs\n14USVI – US Virgin Islands; PR – Puerto Rico\n* Level of  population immunity from prior outbreak in adult population. By 2024, baseline seroprevalence \nhas waned to 28% in population.Variable Value Range Source\nLow High\nBaseline seroprevalence* 31% 18% 42% USVI1 and PR2 data\n% symptomatic among infected 72% 53% 97% USVI data1Infection Inputs\n1. Hennessey MJ, et al. Amer J Trop Med Hyg , 2018; 99:1321- 1321.\n2. Adams LE, et al. PLOS NTD. 2022; 16:e0010416- e0010416.\n15Variable Value Range Source\nLow High\n% care -seeking 43% 30% 82% USVI data1\n% hospitalized*10% 5% 15% USVI data1\n% with chronic joint pain+35% 19% 61% Metanalysis2\n% death^ 1% 0.1% 3% PR data3\nUSVI – US Virgin Islands, PR – Puerto Rico\n* of those seeking care\n+ 6 months after infection\n^ of those hospitalized1Hennessey MJ, et al. Amer J Trop Med Hyg ,  2018; 99:1321- 1321.; \nHennessey MJ, et al. Centers for Disease Control and Prevention, 2015.\n2Lindsey NP. ACIP presentation. 2023\n3Sharp TM, et al. J Infect Dis. 2016; 214: S475- S 481Health Outcome Inputs\n16•Vaccine seroresponse rate of 96.3% (clinical trial data)1\n•Decay in vaccine seroresponse rate of 5 percentage points every 5 years based on \nother live  attenuated or chimeric vaccines2\n1.Schneider M, et al. Lancet. 2023;  401:2138- 2147.\n2.Lindsey NP, et al. J Travel Medicine. 2018; 25:tay108; Desai KL, et al. \nVaccine. 2012; 30:2510- 2515.40%60%80%100%\n2024 2034 2044 2054Seroresponse rateEstimated Vaccine Seroreponse Over Time HorizonVaccine Seroresponse\n17Variable Time Weight\n(range)QALYs Lost\n(range)Source\nNon -hospitalized case*^ 7 days0.63\n(0.19- 0.91)0.01 \n(0.002- 0.016)Dengue1\nHospitalized case* 14 days0.56\n(0.19- 0.91)0.02\n(0.004- 0.031)Dengue1\nChronic joint pain case 1 year0.76\n(0.65- 0.90)0.24\n(0.10- 0.35)Chikungunya and \nrheumatoid \narthritis2,3\nQALY – quality -adjusted life -year; QALY losses due to death are included and include loss \nbeyond time horizon of model \n*Weights for acute disease based on dengue; no weights available for chikungunya^All symptomatic cases had QALY losses regardless of care -seeking behavior QALY Inputs\n1 Zeng W, et al. Am J Trop Med Hyg. 2018; 99:1458- 1465.\n2 Couzigou  B, et al. Am J Trop Med Hyg. 2018; 99:182- 190.\n3 Sorensen J, et al. Value Health. 2012; 15:334- 339\n18Sensitivity Analyses Methods\n19•Univariate (one- way) analysis\n-Varied one parameter at a time and calculated mean $/QALY gained using low (1%) \nand high (99%) values of input distributions\n•Scenario analyses\n-Altered year of outbreak to 2029 or 2039 (base: 2034)\n-Altered halting seroprevalence to 30%1 or 80%2 (base: 40%)\n-Altered vaccination coverage\n•Routine 10% or 30% (base: 20%)\n•Outbreak 50% or 85% (base: 70%)\n1 Hennessey MJ, et al. Amer J Trop Med Hyg, 2018; 99:1321- 1321 & \nAdams LE, et al. PLOS NTD. 2022; 16:e0010416- e0010416\n2 Jamaican MoH. JHLSIII, 2018Sensitivity Analyses\n20Results\n21•Outbreak strategy averts 67% of health outcomes\n•Routine strategy averts 90% of health outcomes\n040,00080,000120,000160,000200,000\nSymptomatic Cases Hospitalizations Chronic joint pain Deaths QALYs lostNo vaccination Outbreak RoutineHeath Outcomes\n\n22•More doses delivered in routine strategy during 30- year time horizon \nthan outbreak strategy\n•Base scenario vaccination costs\n•Routine strategy : $436 million \n•Outbreak strategy : $356 million\n*Vaccination costs include vaccines, administration, and adverse event costs\n   All costs converted to 2023 $USVaccination Doses and Costs*\n23Outcome StrategyTotal costs,\nNo vaccine\n(millions)Total costs,\nVaccine\n(millions)Difference\nSocietal Costs*Routine $566 $496 -12%\nOutbreak $566 $547 -3%\nHealthcare \nPayer Costs^Routine $269 $465 73%\nOutbreak $269 $449 67%\nAll costs converted to 2023 $US\n* Societal costs include vaccination costs, direct medical costs, and indirect costs due to lost productivity. \n^ Healthcare payer costs include vaccination costs and direct medical costs.Total Costs\n24Symptomatic \nCaseHospitalizationChronic joint \npain caseDeath QALY gained\nMean cost per outcome averted [95% CI]\nRoutine \nStrategyCost \nsavingsCost \nsavingsCost\nsavingsCost\nsavingsCost \nsavings\nOutbreak StrategyCost \nsavings$2,315\n[$1K, $4K]$5 \n[Cost savings, \n$200]$373,054\n[$173K, $573K]$59 \n[Cost savings, \n$1K]Cost -effectiveness, Societal Perspective\n25*Presented from societal perspectiveSensitivity Analyses Results*\n26$ 0 $ 5,000 $ 10,000 $ 15,000 $ 20,000Baseline seroprevalence\nProportion symptomatic\nCost medical, chronic joint pain\nProportion hospitalized\nProportion sought care\nVaccine cost\nCost medical, acute case\nProportion chronic joint pain\nTime with joint pain\nCost lost productivity, acute case\nCost per QALY gainedRoutine Strategy\nOutbreak StrategyTop 10 influential inputs, ranked by impact to mean $/QALY gained\nResults not visible where the range \nwas < $0/QALY gainedUnivariate Sensitivity Analysis, Routine Strategy\n27Routine strategy Outbreak strategy\nMean $/QALY gained\n [95% CI]\nOutbreak occurs in 2029 Cost savings$3,829\n[$3K, $4.6K]\nOutbreak occurs in 2039 Cost savings Cost savings\n*Base scenario had outbreak occurring in 2034Sensitivity Analysis for Outbreak Timing*\n28•30% halting seroprevalence: all scenarios have net positive costs \n-Low vaccination has the lowest cost per QALY gained\n•40% halting seroprevalence (base value): high vaccination has net \ncosts, base and low vaccination result in cost savings\n-Low vaccination has the lowest cost per QALY gained\n•80% halting seroprevalence: all scenarios  result in cost savings\n-High vaccination has lowest cost per QALY gainedScenario Analysis Varying Halting Seroprevalence and \nVaccination Coverage*\n*Vaccination Coverage Rates: \nBase vaccination= 20% routine, 70% outbreak; Low vaccination= 10% routine, 50% outbreak; High vaccination= 30% routine, 85% o utbreak \n29Limitations and Summary\n301. No efficacy or effectiveness data available for current vaccine; data planned to be \ngenerated in post- licensure studies\n2.Limited evidence on outbreak frequency (i.e., when and how many) in same \ngeographical locations\n3.QALY health utility weights mostly from dengue as proxy since no weights determined for acute chikungunyaLimitations\n31•Chikungunya vaccine use in US territories would avert 67- 90% of cases and \nassociated health outcomes versus no vaccination\n•Cost of intervention would range from $356 to $436 million depending on strategy \nused\n•Routine strategy had cost savings for each outcome while outbreak strategy had \nmostly net positive costs in base scenario\n•Results most affected by baseline and halting seroprevalenceSummary\n32For more information, contact CDC\n1-800- CDC- INFO (232 -4636)\nTTY:  1 -888- 232- 6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position o f the Centers for Disease Control and \nPrevention.", "summary": "1 Cost -effectiveness of live attenuated chikungunya vaccine among adults  living in US territories Kelly Kilburn, PhD, Martin I. Meltzer, PhD, Seonghye Jeon, PhD, Susan L. Hills, MBBS,  MTH, Bishwa B. Adhikari, PhD, Nicole P. Lindsey, MS, J. Erin Staples, MD, PhD June 27th, 2024 National Center for Emerging Zoonotic and Infectious DiseasesNational Center for Emerging Zoonotic and Infectious Diseases  2•Authors have no known conflict of interests •The findings and conclusions in this…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/04-Chikungunya-Kilburn-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 32}
{"title": "05 Chikungunya Hills 508", "content": "Next steps for the Chikungunya Vaccines Work GroupNational Center for Emerging and Zoonotic Infectious Diseases\nSusan Hills MBBS MTH\nCDC Lead , Chikungunya Vaccines Work Group\nArboviral Diseases Branch\nDivision of Vector -Borne Diseases\nFort Collins, Colorado\nACIP Meeting, June 26, 2024\n•Work Group gathering data and will discuss additional important \nconsiderations including:\n-Acceptability and value of vaccine to providers and relevant populations\n-Feasibility of administration Consideration of recommendations for use of \nchikungunya vaccine in at -risk U.S. territories \nPlans for development of vaccine recommendations\nPopulations Live \nattenuated vaccine\nTravelers Feb 2024\nLaboratory workers Feb 2024\nResidents of U.S. territories with risk \nResidents of U.S. states with risk \nPlans for development of vaccine recommendations\nPopulations Live \nattenuated vaccineVirus -like \nparticle vaccine\nTravelers Feb 2024 \nLaboratory workers Feb 2024 \nResidents of U.S. territories with risk  \nResidents of U.S. states with risk  ", "summary": "Next steps for the Chikungunya Vaccines Work GroupNational Center for Emerging and Zoonotic Infectious Diseases Susan Hills MBBS MTH CDC Lead , Chikungunya Vaccines Work Group Arboviral Diseases Branch Division of Vector -Borne Diseases Fort Collins, Colorado ACIP Meeting, June 26, 2024 •Work Group gathering data and will discuss additional important  considerations including: -Acceptability and value of vaccine to providers and relevant populations -Feasibility of administration Consideration…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/05-Chikungunya-Hills-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 4}
{"title": "01 Denvaxia Bergren 508", "content": "June 26 – ACIP Meeting\nDengvaxia®Next Steps\nNicholas Bergren PhD, MBA\nDirector, Scientific and Medical Affairs\n1\nInternal\n22021  ACIP  Recommendation  for Dengvaxia®:\nACIP recommends  vaccination  with the Dengvaxia® vaccine  for children  aged 9–16 years  \nhaving  evidence  of a previous  dengue  infection  and living  in areas  where  dengue  is endemic . \nDengvaxia® is recommended  as a 3-dose vaccination  series,  administered  6 months  apart  (at \nmonth  0, 6, and 12)for the selected  pediatric  population . Evidence  of previous  dengue  \ninfection,  such as confirmation  with previous  laboratory -confirmed  infection  or a highly  \nspecific  serodiagnostic  test, will be required  among  eligible  children  before  vaccination .Dengvaxia® Indication, Schedule & Recommendation\nUSPI  Indication :\nFor the prevention  of dengue  disease  caused  by dengue  virus serotypes  1, 2, 3 and 4. \nDengvaxia® is approved  for use in individuals  6 through  16 years  of age with laboratory -\nconfirmed  previous  dengue  infection  and living  in endemic  areas .\nUSPI  Dosage  and Administration :\nThree  doses  (0.5 mL each)  6 months  apart  (at month  0, 6, and 12).\nInternal\n3Dengvaxia® has been available globally since 2015 and was recommended by ACIP in 2021:\n▪Efforts have been made to facilitate implementation of the ‘Screen & Vaccinate’ approach as recommended by \nWHO in 2018, however demand for Dengvaxia®has been andcontinues to remain low globally and in Puerto Rico.\n▪Despite an increased incidence of dengue in different parts of the world, Puerto Rico's Dengvaxia®Immunization \nProgram is the only public program currently in place.\n▪Dengvaxia®is indicated for people with prior dengue infection and requires a 1 -year vaccination schedule to \ncomplete the primary series.\n▪Dengvaxia®is not intended for acute dengue outbreak control.Dengvaxia®Next Steps\nDengue Tetravalent Vaccine (Live, Attenuated)  [Dengvaxia®] is being discontinued due to low demand.\nThis decision is not due to any concerns regarding quality, safety or efficacy.\nWe have worked early with and continue to collaborate with the CDC to facilitate product utilization.\nDengvaxia® will continue to be distributed through public (e.g., VFC) and private markets globally (including \nPuerto Rico where it is currently recommended by the ACIP) through product expiry.\nThe last doses of Dengvaxia®will expire at the end of August 2026. Given the 3-dose, 1 -year series needed for \nfull immunization, individuals should start the Dengvaxia® immunization series no later than August 31, 2025.\n \nThank you", "summary": "June 26 – ACIP Meeting Dengvaxia®Next Steps Nicholas Bergren PhD, MBA Director, Scientific and Medical Affairs 1 Internal 22021  ACIP  Recommendation  for Dengvaxia®: ACIP recommends  vaccination  with the Dengvaxia® vaccine  for children  aged 9–16 years   having  evidence  of a previous  dengue  infection  and living  in areas  where  dengue  is endemic .  Dengvaxia® is recommended  as a 3-dose vaccination  series,  administered  6 months  apart  (at  month  0, 6, and 12)for the selected …", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/01-Denvaxia-Bergren-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 4}
{"title": "02 Dengue Wong 508", "content": "Update on Dengue Vaccines\nJoshua Wong, MD \nMedical Officer | NCEZID/DVBD/Dengue Branch\nMeeting of the Advisory Committee on Immunization Practices\nJune 26, 2024National Center for Emerging and Zoonotic Infections\n1\nDengue Epidemiology Globally\nCountries reporting locally acquired dengue cases, \nMarch 2023 –April 2024 \nImage from: https://www.ecdc.europa.eu/en/publications -data/countriesterritories -reporting -dengue -cases -march -2023 -and-april -2024 . Accessed 6/1/2024\nDengue cases in the Americas, 1980 –2024  \nNearly 10 million cases reported in 2024 as of June 25.\nData from PAHO PLISA Health Information Platform for the Americas. https://www3.paho.org/data/index.php/es/temas/indicadores -dengue.html . Accessed 6/25/202402,000,0004,000,0006,000,0008,000,00010,000,00012,000,000Number of dengue cases\nYear\nDengue Epidemiology in the U.S.\nIn the United States, dengue is endemic in\n6U.S. territories and freely associated states.\n\nPuerto Rico declared a public health emergency \ndue to a dengue epidemic in March 2024.\nWeekly Arboviral Report – Week 23, Puerto Rico Department of Health, accessed 6/25/2024. https://www.salud.pr.gov/CMS/DOWNLOAD/9050  \n2023 cases 2024 cases Historic median Epidemic thresholdDENV infections in \nPuerto Rico have \nbeen above the \nepidemic threshold \nfor 21 weeks.x 21 weeksNumber of cases\nWeek\nUpdate on Dengvaxia in Puerto Rico\nThe first dengue \nvaccine in Puerto \nRico was \nadministered on \nSeptember 7, \n2022.\nImages from: https://www.elvocero.com/actualidad/salud/administran -la-primera -vacuna -contra -el-\ndengue/article_9c49436a -2e4f -11ed -beba -0bf2bccaeb1f.html Accessed 6/12/2024. \nSince Dengvaxia vaccination began in Puerto Rico,\n264 doses have been administered.*\n13149264\n050100150200250300\n1 2 3Number of Doses  of Dengvaxia\nAdministered (cumulative) \nYear\nData used with permission from the Puerto Rico Department of Health, Vaccine Program. Current as of June 24, 2024.\nSince Dengvaxia vaccination began in Puerto \nRico, 145 individuals have started the series. \n145\n87\n32\n020406080100120140160\n1 2 3Number of Doses  of Dengvaxia \nAdministered (cumulative) \nData used with permission from the Puerto Rico Department of Health, Vaccine Program. Current as of June 24, 2024.\nPhysician visit #1:\nInitial evaluationLaboratory \ntestingPhysician visit #2:\nResults follow -upVaccine clinic visit\nSchedule 2nd and 3rd dosesMultiple visits to healthcare providers to determine eligibility \nand start vaccination has complicated implementation.\nMajor barriers to uptake have included:  \nPrevaccination  \nTesting\nLimited vaccine \nmessaging  \nComplex billing \nprocesses\nCDC has updated its website with information \non discontinuation of Dengvaxia. \nDengue Vaccine | Dengue | CDC\nUpdate on Other Dengue Vaccines in the U.S.\nTakeda voluntarily withdrew TAK -003 (Qdenga) from \nFDA review in July 2023.\nTakeda/Newsroom\nThe TV003/TV005 dengue vaccine is in late-stage \nphase 3 trials.\n•Developed by the US National Institutes of Health (NIH).\n•Licensed to Merck in the U.S. and the Instituto Butantan  in \nBrazil.\n•Phase 3 trials in Brazil are ongoing.\n•High efficacy and safety results during the first two year \nfollow -up period have been published.*\n•DENV -3 or DENV -4 not observed during this period, \nlimiting evaluation of VE against these serotypes.\n•Five year follow -up data expected later this year.\n*Kallás , E. G., et al. (2024). \"Live, Attenuated, Tetravalent Butantan -Dengue Vaccine in Children and Adults.\" N Engl J Med 390(5): 397 -408.\nImage from: https://revistapesquisa.fapesp.br/en/butantans -dengue -vaccine -is-80-effective/  accessed 6/11/2024.\n\nNo dengue vaccines will be available in the \nU.S. after the discontinuation of Dengvaxia. \n•No dengue vaccines are currently under \nreview by FDA.\n•The ACIP Dengue Vaccines Workgroup \ngroup will be paused until new dengue \nvaccines are submitted to FDA for \napproval.\n\nConclusion \n•Dengue cases globally are increasing.\n•Puerto Rico has declared a public health emergency due to the \ndengue epidemic.\n•There will be no other vaccines available in the U.S. after \nDengvaxia manufacturing is discontinued.\n•The Dengue Vaccines Workgroup will be paused until new \nvaccines are submitted for FDA review.\n•Vaccines are just one part of a multilayered approach to \nreducing morbidity by dengue.\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the \nofficial position of the Centers for Disease Control and Prevention.\nACIP Members\nWilbur Chen (Chair)\nKathy Poehling\nBeth Bell\nVeronica McNally\nCDC Co -Leads\nGabriela Paz -Bailey\nLaura Adams\nEx Officio Members\nKaitlyn Morabito (NIH)\nRalph LeBlanc (FDA)\nIhid Carneiro Leao (FDA)\nKirk Prutzman (FDA)\nSrihari Seshadri  (DOD)\nLiaison  Representatives\nElizabeth  Barnett  (AAP)\nRob Schechter  (AIM)Consultants\nEdwin  Asturias\nRobert  Atmar\nAlan  Barrett\nIris Cardona\nAnna  Durbin\nTony  Marfin\nKristen  Pierce\nAnita  Shet\nCDC Contributors\nJoshua Wong\nNicole Medina\nMimi Eckert\nRachel Eidex\nAlfonso Hernandez\nSusan Hills\nTerri Hyde\nMike McNeil\nJorge MunozErin Staples\nCindy Weinbaum\nRita Helfand\nNon -Members\nMitchelle Flores -Febo\nParker Acevedo\nDiana Duran\nAngel RiveraQuestions?ACIP Dengue Vaccines Workgroup and Support Team", "summary": "Update on Dengue Vaccines Joshua Wong, MD  Medical Officer | NCEZID/DVBD/Dengue Branch Meeting of the Advisory Committee on Immunization Practices June 26, 2024National Center for Emerging and Zoonotic Infections 1 Dengue Epidemiology Globally Countries reporting locally acquired dengue cases,  March 2023 –April 2024  Image from: https://www.ecdc.europa.eu/en/publications -data/countriesterritories -reporting -dengue -cases -march -2023 -and-april -2024 . Accessed 6/1/2024 Dengue cases in the…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/02-Dengue-Wong-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 21}
{"title": "01 COVID Daley 508", "content": "ACIP COVID -19 Vaccines Work Group\nDr. Matthew F. Daley, Work Group Chair\nJune 27, 2024National Center for Immunization and Respiratory Diseases\n\n•ACIP met September 12, 2023 and recommended 2023 -2024 COVID -19 vaccines as authorized \nunder EUA or approved by BLA in persons aged ≥6 months​\n-Moderna COVID -19 vaccine in persons ≥6 months ​\n-Pfizer -BioNTech COVID -19 vaccine in persons ≥6 months ​\n-Novavax COVID -19 vaccine in persons ≥ 12 years*​\n•Everyone aged 5 years and older should get 1 dose of a 2023 -2024 COVID -19 vaccine to protect \nagainst serious illness from COVID -19\n•Children aged 6 months –4 years need multiple doses of COVID -19 vaccines to be up to date, \nincluding at least 1 dose of 2023 -2024 COVID -19 vaccine\n•People who are moderately or severely immune compromised may receive additional doses of \nCOVID -19 vaccines\n•On February 28, 2024 ACIP recommended that adults ages 65 years and older receive one additional \n2023 -2024 COVID -19 vaccine dose2023 -2024 COVID -19 vaccine recommendations \nAbbreviations – EUA: Emergency Use Authorization, BLA: Biologics License Application\n*People aged 12 years and older who have not previously received any COVID -19 vaccine doses and choose to get Novavax should get  2 doses of updated Novavax vaccine to be up to date.\n•Reviewed evidence to inform recommendations for an additional dose of the 2023 -2024 \nCOVID -19 vaccine for adults ages 65 years and older, including:\n-COVID -19 hospitalizations\n-COVID -19 vaccine coverage\n-COVID -19 vaccine effectiveness\n-Economic analysis of additional COVID -19 vaccine doses\n-Evidence to Recommendations\n•ACIP voted to recommend an additional dose of 2023 -2024 COVID -19 vaccine in persons ≥65 \nyears\n•Discussed next steps for the COVID -19 vaccine program, including shifting to a vote at the June \nACIP meeting for future vaccine updatesFebruary 2024 ACIP Meeting Review\n•Framing of the policy question for the 2024 -2025 vaccine\n-Started with considerations for universal v. risk -based recommendations\n•Reviewed international COVID -19 vaccination policies from countries with \nrisk-based and age -based recommendations\n•Discussed complexity of a risk -based recommendation, including \n–Defining risk groups for severe outcomes \n–Whether to take into account high risk of exposure \n–Recommendations for persons not meeting risk criteria, including \nthose not previously vaccinated\n•Discussed i mplementation challenges of non -universal policy options \n-Work Group consensus was to proceed with deliberations for a universal \nrecommendation for everyone ages ≥ 6 months for 2024 -2025 vaccineACIP COVID -19 Work Group Meeting Review – \nInitial planning  \n•Framing of the policy question for the 2024 -2025 vaccine\n•Updated data on COVID -19 epidemiology, including risk factors for hospitalization due to \nCOVID -19 and epidemiology of Multisystem Inflammatory Syndrome in Children (MIS -C) and \nPost -COVID Conditions\n•Vaccine effectiveness of the 2023 -2024 COVID -19 vaccine\n•Review of COVID -19 vaccine safety including longer -term outcomes of myocarditis \n•Economic analysis of COVID -19 vaccination\n•COVID -19 vaccine program implementation considerations\n•Evidence to Recommendations Framework ACIP COVID -19 Work Group Meeting Review\nMarch – June 2024\n•June 5, 2024: FDA’s Vaccines and Related Biological Products Advisory \nCommittee (VRBPAC) met to discuss strain selection for 2024 -2025 COVID -\n19 vaccines\n-Based on the totality of the evidence presented, FDA advised \nmanufacturers to develop monovalent JN.1 lineage COVID -19 vaccines, \nwith a preference for the KP .2 strain, if feasible\n-Anticipated 2024 -2025 vaccine doses will be broadly available in the fallCOVID-19 vaccine 2024-2025 Formula: VRBPAC Meeting\nhttps://www.fda.gov/vaccines -blood -biologics/updated -covid -19-vaccines -use-united -states -beginning -fall-2024  \nCOVID -19-associated hospitalizations \nCOVID-19 vaccine effectiveness update \nVaccine safety update for 2023-2024 COVID-19 vaccine \nEconomic analysis of COVID-19 vaccination \nEvidence to recommendations \nCOVID-19 vaccine implementation   Dr. Fiona Havers\n  Dr. Ruth Link -Gelles\nDr. Jonathan Duffy\n Dr. Lisa Prosser\n  Dr. Lakshmi Panagiotakopoulos\n  Dr. Shannon Stokely\nVote: 2024 -2025 COVID -19 vaccines in persons ages 6 months and olderAgenda: June 27, 2024\nWork Group members\nACIP members\n•Matthew Daley (chair)\n•Oliver Brooks\n•Robert Schechter\n•Keipp Talbot\nEx-officio/government members\n•BARDA: Christine Oshansky\n•CDC: Alan Lam\n•FDA: Rachel Zhang, Adam Spanier\n•IHS: Uzo Chukwuma\n•NIH: Chris Roberts\nCDC co -Leads\n•Megan Wallace\n•Lakshmi PanagiotakopoulosLiaisons\n•AAFP: Jonathan Temte\n•AAP: Sean O’Leary\n•ACOG: Naima Joseph (primary), \nLaura Riley (alternate)\n•ACP: Jason Goldman\n•AGS: Ken Schmader\n•AIM: Heather Roth\n•AMA: Sandra Fryhofer\n•ANA: Ruth Francis \n•APhA : Richard Dang\n•ASTHO: Marcus Plescia\n•CSTE: Paul Cieslak, Christine Hahn\n•IDSA: Jeff Duchin Liaisons, cont’d\n•NACCHO: Matt Zahn (primary), \nJeff Duchin (alternate)\n•NACI: Eva Wong (primary), \nMatthew Tunis (alternate)  \n•NFID: Robert Hopkins (primary),   \nBill Schaffner (alternate) \n•SHEA: Preeti Mehrotra (primary),                \nMarci Drees (alternate)\n   \nConsultants\n•Beth Bell\n•Ed Belongia  \n•Hank Bernstein  \n•Kathy Edwards  \n•Lisa Jackson\n•Kathy Kinlaw•Grace Lee\n•Dayna Matthew\n•Jennifer Nelson\n•Stanley Perlman\n•Peter Szilagyi\nCDC participants \n•Sarah Meyer\n•Elisha Hall\n•Danielle Moulia\n•Monica Godfrey\n•Hannah Rosenblum\n•Katherine Fleming -Dutra\n•Ruth Link -Gelles\n•Lauren Roper \n•Mary Chamberland\n•Susan Goldstein\n•Stephen Hadler\n•JoEllen Wolicki\n•Melinda Wharton\n•Jessica MacNeil\n•Latifa Boyce \n•Amadea Britton\n•Karen Broder•Carolyn Bridges\n•Allison Ciesla \n•Nicole Dowling\n•Daniel Drapeau\n•Kristen Folsom\n•Ashley Fowlkes\n•Jarrett Gartin\n•Julianne Gee\n•Samuel Graitcer\n•Elizabeth Greene\n•Lisa Grohskopf\n•Aron Hall \n•Demorah Hayes\n•Rita Helfand\n•Michele Hlavsa\n•Terri Hyde \n•Jefferson Jones\n •Andrew Kroger\n•Josephine Mak\n•Lauri Markowitz\n•Michael McNeil\n•Michael Melgar\n•Noelle -Angelique Molinari\n•Morgan Najdowski\n•Kristen Nordlund\n•Ismael Ortega -Sanchez\n•Manisha Patel\n•Pragna Patel\n•Amanda Payne\n•Georgina Peacock\n•Jamison Pike\n•Derrell Powers  \n•Sierra Scarbrough \n•Jordan Singleton•Laura Steinhardt\n•John Su\n•Natalie Thornburg\n•Evelyn Twentyman \n•David Wentworth\n•Dennis Wang\n•Raigan Wheeler\n•Ryan Wiegand\n•Trang Wisard\n•Patricia Yu\n•Yon Yu\nFor more information, contact CDC\n1-800-CDC-INFO (232- 4636)\nTTY:  1- 888- 232-6348    cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the U.S. Centers for Disease Control and Prevention.", "summary": "ACIP COVID -19 Vaccines Work Group Dr. Matthew F. Daley, Work Group Chair June 27, 2024National Center for Immunization and Respiratory Diseases  •ACIP met September 12, 2023 and recommended 2023 -2024 COVID -19 vaccines as authorized  under EUA or approved by BLA in persons aged ≥6 months​ -Moderna COVID -19 vaccine in persons ≥6 months ​ -Pfizer -BioNTech COVID -19 vaccine in persons ≥6 months ​ -Novavax COVID -19 vaccine in persons ≥ 12 years*​ •Everyone aged 5 years and older should get 1…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/01-COVID-Daley-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 10}
{"title": "02 COVID Havers 508", "content": "Centers for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nCOVID -19–Associated Hospitalizations among \nChildren and Adults — COVID -NET\nACIP Meeting\nFiona P . Havers, MD, MHS\nRESP -NET Hospitalization Surveillance Team\nSurveillance and Prevention Branch\nCoronavirus and Other Respiratory Viruses Division\n▪RESP -NET: COVID -NET, RSV -NET, FluSurv -NET\n▪>300 acute -care hospitals\n▪98 counties in 13 states\n▪In 9 of 10 HHS regions\n▪~10% of U.S. population\n▪Positive SARS -CoV-2 within 14 days of or \nduring hospitalization\n▪Screening or clinician -driven testing\n▪Clinical data: representative sample of \nCOVID -NET patientsCOVID -NET: A RESP -NET population -based hospitalization \nsurveillance platform\n\nPopulation -Based Rates of COVID -19-Associated \nHospitalizations — COVID -NET, March 2020 –May 2024\n020406080100120140160\n3/7/2020\n5/7/2020\n7/7/2020\n9/7/2020\n11/7/2020\n1/7/2021\n3/7/2021\n5/7/2021\n7/7/2021\n9/7/2021\n11/7/2021\n1/7/2022\n3/7/2022\n5/7/2022\n7/7/2022\n9/7/2022\n11/7/2022\n1/7/2023\n3/7/2023\n5/7/2023\n7/7/2023\n9/7/2023\n11/7/2023\n1/7/2024\n3/7/2024\n5/7/2024Rate per 100,000 population\nWeek Ending DateWeekly Rates: March 2020 –May 2024\n<6 months 6 months –4 years 5–11 years 12–17 years\n18–49 years 50–64 years 65–74 years ≥75 yearsRates highest in ≥75 years, followed by \ninfants <6 months and adults 65 –74 years01002003004005006007008009001000Rate per 100,000 populationCumulative Rates: Oct 2023 –May 2024\n020406080100120140160180200\n10/7/2023 11/7/2023 12/7/2023 1/7/2024 2/7/2024 3/7/2024 4/7/2024 5/7/2024COVID -19-Associated Hospitalization Rate\nper 100,000 population\nWeek ending date\nWhite, non-Hispanic Black, non-Hispanic\nAmerican Indian/Alaska Native, non-Hispanic Asian/Pacific Islander, non-Hispanic\nHispanicAge -Adjusted Cumulative Rates of COVID -19-Associated Hospitalizations \nby Race and Ethnicity, All Ages — COVID -NET, October 2023 –May 2024\nPercent of Weekly Hospitalizations by Age Group —\nCOVID -NET, March 2020 –May 2024\n0%10%20%30%40%50%60%70%80%90%100%\n3/7/2020\n4/11/2020\n5/16/2020\n6/20/2020\n7/25/2020\n8/29/2020\n10/3/2020\n11/7/2020\n12/12/2020\n1/16/2021\n2/20/2021\n3/27/2021\n5/1/2021\n6/5/2021\n7/10/2021\n8/14/2021\n9/18/2021\n10/23/2021\n11/27/2021\n1/1/2022\n2/5/2022\n3/12/2022\n4/16/2022\n5/21/2022\n6/25/2022\n7/30/2022\n9/3/2022\n10/8/2022\n11/12/2022\n12/17/2022\n1/21/2023\n2/25/2023\n4/1/2023\n5/6/2023\n6/10/2023\n7/15/2023\n8/19/2023\n9/23/2023\n10/28/2023\n12/2/2023\n1/6/2024\n2/10/2024\n3/16/2024\n4/20/2024Percent of COVID -19-associated hospitalizations\nWeek ending date\n≤17 years 18–49 years 50–64 years 65–74 years 75–84 years ≥85 yearsDuring\nOctober 2023 –\nMay 2024:\n•≥65: 67%  of COVID -19 \nhospitalizations\n•<65: 33%  of COVID -19 \nhospitalizations\n•≥75: 46%  of COVID -19 \nhospitalizations\n•≤17: 4% of COVID -19 \nhospitalizations\nEpidemiology of COVID -19–associated \nhospitalizations among infants, children \nand adolescents\n0102030405060708090100Rate per 100,000 population\nWeek Ending Date\n<6 months 6 months –4 years 5–11 years 12–17 yearsPopulation -Based Rates of COVID -19-Associated \nHospitalizations among Children and Adolescents Ages\n≤17 Years — COVID -NET, March 2020 –May 2024\n050100150200250300350 Weekly Rates, March 2020 –May 2024 Cumulative Rates\nOctober 2023 –May 2024\n024681012Rate per 100,000 population\nWeek Ending Date\n6 months –4 years 5–11 years 12–17 yearsPopulation -Based Rates of COVID -19-Associated \nHospitalizations among Children and Adolescents Ages\n6 months –17 Years — COVID -NET, March 2020 –May 2024\n0102030405060 Weekly Rates, March 2020 –May 2024 Cumulative Rates\nOctober 2023 –May 2024\nUnderlying Medical Conditions among Infants and Children Ages ≤4 \nYears with COVID -19-associated Hospitalization, by Age Group — \nCOVID -NET, July 2023 –March 2024\n051015202530354045\n<6 months 6–<2 years 2–4 yearsWeighted % of hospitalizations\nAsthma/Reactive airway disease Neurologic disorders Feeding tube dependence\nCardiovascular disease Obesity Immunocompromising condition\nChronic lung disease* Blood disorders Prematurity\nData are limited to hospitalizations where COVID -19 is a likely primary reason for admission. \n* Not including not asthma or reactive airway disease. Among children <2 years old, chronic lung disease includes bronchopulm onary dysplasia and chronic lung disease of prematurity. •50% of infants, \nchildren, and \nadolescents ages ≤17 \nyears with COVID -19-\nassociated \nhospitalization have \nno underlying \nmedical conditions .<6 months:\n75% with no underlying \nconditions6 months –<2 years:\n58% with no underlying \nconditions2–4 years:\n36% with no underlying conditions\nPercent of COVID -19-Associated Hospitalizations with Underlying Medical \nConditions among Children and Adolescents Ages 5 –17 Years with COVID -19-\nassociated Hospitalizations, by Age Group — COVID -NET, July 2023 –March 2024\n47\n303836\n21191822\n19\n131517\n1311\n814\n05101520253035404550\n5–11 years 12–17 yearsWeighted % of hospitalizations\nAsthma Neurologic disorders\nFeeding tube dependence Cardiovascular disease\nObesity Immunocompromising condition\nChronic lung disease, not including asthma Blood disorders\nData are limited to hospitalizations where COVID -19 is a likely primary reason for admission.\nOnly the most common underlying conditions are presented.•50% of infants, \nchildren, and \nadolescents ages ≤17 \nyears with COVID -19-\nassociated \nhospitalization have \nno underlying medical \nconditions .\n•Among COVID -19-\nassociated \nhospitalizations, \nchildren and \nadolescents ages ≥5 \nyears are more likely \nto have underlying \nmedical conditions \nrelative to infants and \nchildren ages ≤4 years.5–11 years:\n20% with no underlying \nconditions12–17 years:\n22% with no underlying \nconditions\nAge categoryAmong all \nhospitalized \nchildren, % with \nno underlying \nconditionsAmong those \nadmitted to ICU, % \nwith no underlying \nconditions\n(n=363)\n<6 months 75% 56%\n6–23 months 58% 52%\n2–4 years 32% 28%\n5–11 years 16% 4%\n12–17 years 18% 19%\nOverall ≤17 Years 50% 40%Underlying Medical Conditions among Patients Admitted to ICU among \nChildren and Adolescents Ages ≤17 Years with COVID -19-associated \nHospitalization, July 2023 –March 2024\nAmong those with no \nunderlying conditions, \nwhat % were admitted \nto ICU?\n(n=791)\n18%\n17%\n20%\n5%\n28%\n18%\nHospitalizations are limited to those with COVID -19 as a likely primary reason for admission.\nVaccination Status among Children and Adolescents Ages ≤17 \nYears with COVID -19-associated Hospitalizations, by Age Group \n— COVID -NET, October 2023 –March 2024\nNo record of bivalent or 2023 –2024 vaccine dose : No recorded doses of COVID -19 bivalent or the 2023 -2024 vaccine dose since August 2022. Bivalent booster, but no 2023 –2024 vaccine \ndose : Received COVID -19 bivalent booster vaccination but no record of receiving 2023 -2024 vaccine dose since August 2022. 2023–2024 vaccine dose: Received 2023 -2024 vaccine dose. \nPersons with unknown vaccination status are excluded. Hospitalizations are limited to those with COVID -19 as the presenting complaint upon admission.86\n80 79\n917 18\n63 3\n0102030405060708090\n6 months –4 years 5–11 years 12–17 yearsPercent of hospitalizations\nNo record of bivalent or 2023 –2024 vaccine dose\nBivalent booster, but no 2023 –2024 vaccine dose\n2023 –2024 vaccine dose•5% of children and \nadolescents ages \n≤17 years with \nCOVID -19-\nassociated \nhospitalizations \nreceived a 2023 –\n2024 vaccine dose.\nEpidemiology of COVID -19–associated \nhospitalizations among adults\nWeekly Population -Based Rates of COVID -19-Associated \nHospitalizations among Adults Ages ≥18 Years — COVID -NET, \nMarch 2020 –May 2024\n020406080100120140160\n3/7/2020 3/7/2021 3/7/2022 3/7/2023 3/7/2024Rate per 100,000 population\nWeek Ending Date\n18–49 years 50–64 years 65–74 years ≥75 years020040060080010001200\n10/7/2023\n11/7/2023\n12/7/2023\n1/7/2024\n2/7/2024\n3/7/2024\n4/7/2024\n5/7/2024Rate per 100,000 populationWeekly Rates, March 2020 –May 2024 Cumulative Rates\nOctober 2023 –May 2024\n1521\n1722\n191824\n1623\n0510152025\nJan-Mar 2022 Apr-Jun 2022 Jul-Sep 2022 Oct-Dec 2022 Jan-Mar 2023 Apr-Jun 2023 Jul-Sep 2023 Oct-Dec 2023 Jan-Mar 2024Weighted % of COVID -19-Associated HospitalizationsPercent of COVID -19-associated hospitalizations admitted from a long -term care facility \namong adults ages ≥65 years, by quarter — COVID -NET, January 2022 –March 2024During January 2022 –March 2024, 19% of COVID -19-associated hospitalizations \namong adults ages ≥65 years were residents of a long -term care facility.\nCumulative In -Hospital Death Rate during COVID -19-Associated \nHospitalization per 100,000 Population by Age Group — \nCOVID -NET, October 2023 –March 2024\n0.562762\n010203040506070\n18–49 years 50–64 years 65–74 years ≥75 yearsIn-hospital death rate per \n100,000 population\nAge group\n18–49 years 50–64 years 65–74 years ≥75 years\n3% 15% 32% 50%Weighted \npercent of in -\nhospital deaths \nby age group\nVaccination Status among Adults Ages ≥18 Years with COVID -19-\nassociated Hospitalization, by Age Group — COVID -NET, October \n2023 –March 2024\n78\n65\n58\n48\n19293436\n36816\n0102030405060708090\n18–49 years 50–64 years 65–74 years ≥75 yearsPercent of hospitalizations\nNo record of bivalent or 2023 –2024 vaccine dose\nBivalent booster, but no 2023 –2024 vaccine dose\n2023 –2024 vaccine dose\nNo record of bivalent or 2023 –2024 vaccine dose : No recorded doses of COVID -19 bivalent or 2023 -2024 vaccine dose since August 2022. Bivalent booster, but no 2023 –2024 vaccine dose : \nReceived COVID -19 bivalent booster vaccination but no record of receiving 2023 –2024 vaccine dose since August 2022. 2023–2024 vaccine dose: Received 2023 -2024 vaccine dose. Persons \nwith unknown vaccination status are excluded. •11% of adults ages \n≥18 years with \nCOVID -19-associated \nhospitalizations \nreceived a 2023 –\n2024 vaccine dose.\n•57% of COVID -19-\nassociated \nhospitalizations \namong adults ages \n≥18 years had not \nreceived a COVID -19 \nvaccine after August \n2022.\nPercent of COVID -19-associated Hospitalizations among Adults Ages ≥18 Years with \nUnderlying Medical Conditions, by Age Group, with Top 4 Categories Highlighted — \nCOVID -NET, July 2023 –March 2024\nCondition 18–49 years 50–64 years 65–74 years ≥75 years\nChronic lung disease 26 41 51 40\nAsthma 19 17 17 10\nCOPD/Bronchitis 4 19 30 19\nCardiovascular disease 26 56 65 72\nCAD/CABG/MI 4 18 34 32\nCHF/Cardiomyopathy 8 23 29 29\nStroke/TIA 5 18 13 20\nDiabetes 19 41 40 34\nImmunocompromising condition 12 22 22 11\nNeurologic condition 23 32 29 46\nRenal Disease 12 25 25 33\nSevere obesity (BMI ≥40 kg/m²) 16 14 6 3\nCOPD: chronic obstructive pulmonary disease; CAD: coronary artery disease; CABG: coronary artery bypass graft; TIA: transient  ischemic attack\nPink cells indicate the 4 most common underlying medical conditions within each age group; dark pink cells indicate the most com mon condition.\nWe used 3 data sources to calculate COVID -19–associated \nhospitalization rates by chronic condition and age group\nNumerator\n Denominator\n•COVID -19–Associated Hospitalization \nSurveillance Network (COVID –NET)•Behavioral Risk Factor Surveillance \nSystem (BRFSS)\n•Census population counts\nPrevalence of chronic conditions among hospitalized adults in COVID -NET,\nadults in COVID -NET states, and adults in the United States aged ≥18 years, 2022\nData are preliminary and subject to change. Obesity is defined as BMI 30 –39 kg/m²; severe obesity is defined as BMI ≥40 kg/m². O nly includes community dwelling residents. Non -community \ndwelling persons, including those who resided in a long -term care facility upon admission, are excluded. COVID -19-related admiss ions are those where the primary reason for admission is \nCOVID -19-related illness. Prevalence data from COVID -NET states and United states are obtain from the Behavioral Risk Factor Sur veillance System, 2022 data.\n•Except for asthma and obesity, \nunadjusted prevalence is higher \namong hospitalized COVID -19 \npatients relative to the general \npopulation\n•In adjusted models, except for \nobesity, all other 8 conditions \nexamined were found to increase \nthe risk for COVID -19-associated \nhospitalization.\n•Magnitude of increased risk \nvaried by condition and age \ngroup.\n•Age ≥75 remains a strong risk \nfactor for hospitalization even in \nadjusted models\n•Results are limited to community -\ndwelling adultsUnadjusted prevalence (%)\nwith 95% confidence intervals\n▪Rates of COVID -19-associated hospitalizations highest among those \n≤4 years\n▪Rates highest among infants ages <6 months who are not vaccine \neligible and require a different approach for prevention (e.g., \nmaternal vaccination)\n▪50% have no underlying medical conditions\n•Among children with no underlying medical conditions, 18% were \nadmitted to the ICU\n▪October 2023 –March 2024: 5% of hospitalized children 6 months –  ≤ \n17 years had received a 2023 –2024 vaccine prior to admissionSummary – Infants, Children, and Adolescents\n▪2/3 of all COVID -19-associated hospitalizations among those aged \n≥65 years\n▪During October 2023 –March 2024, 11% of hospitalized adult patients \nhad received a 2023 –2024 vaccine dose prior to admission\n▪Underlying conditions increase risk for hospitalization, but age \nremains strongly associated with the risk for hospitalizationSummary – Adults \nCoronavirus and Other Respiratory \nViruses Division\nChris Taylor\nHuong Pham\nSarah Hamid\nGordana Derado\nMegan Wallace\nLakshmi Panagiotakopoulos \nKatherine Fleming -DutraOther CDC staff\nRebecca Woodruff\nRESP -NET Site investigators and staffAcknowledgements\nFor more information, contact CDC\n1-800 -CDC -INFO (232 -4636)\nTTY:  1 -888 -232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention.\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.", "summary": "Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. COVID -19–Associated Hospitalizations among  Children and Adults — COVID -NET ACIP Meeting Fiona P . Havers, MD, MHS RESP -NET Hospitalization Surveillance Team…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/02-COVID-Havers-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 24}
{"title": "03 COVID Link Gelles 508", "content": "Effectiveness of COVID -19 (2023-2024 Formula) \nvaccines \nRuth Link-Gelles, PhD, MPH\nCDR, US Public Health Service\nVaccine Effectiveness Program Lead\nCoronavirus and Other Respiratory Viruses Division\nCenters for Disease Control and Prevention \nJune 27, 2024National Center for Immunization and Respiratory Diseases \n\n•Vaccine effectiveness (VE) methods refresher\n•Context for interpretation of COVID -19 VE\n•COVID -19 VE in adults, by outcome and variant:\n-Symptomatic SARS -CoV-2\n-COVID -19-associated emergency department/urgent care (ED/UC) encounters\n-COVID -19-associated hospitalizations, by immunocompromise status\n-COVID -19-associated critical outcomes\n•COVID -19 VE in young children and by age groupAgenda: effectiveness of \nCOVID-19 ( 2023 -2024  Formula) vaccines\nCase ControlPerson with acute\nrespiratory illness\nPathogen test\n(e.g., SARS-CoV-2, RSV, etc.)\nImmunization\nstatus\nObservational effectiveness\nmeasured in a test-negative design (TND) study\n𝑂𝑑𝑑𝑠 𝑜𝑓 𝑖𝑚𝑚𝑢𝑛𝑖𝑧𝑎𝑡𝑖𝑜𝑛Effectiveness = 1 –  (odds ratio) x 100%    Odds ratio = 𝑐𝑎𝑠𝑒𝑠\n𝑂𝑑𝑑𝑠 𝑜𝑓 𝑖𝑚𝑚𝑢𝑛𝑖𝑧𝑎𝑡𝑖𝑜𝑛 𝑐𝑜𝑛𝑡𝑟𝑜𝑙𝑠Key features of a TND\n•Real -world circumstances\n•Study start is symptomatic medical encounter\n•Heterogenous study population,\noften “all comers”\n•Benefits\n•Reduces bias from health -care seeking behavior by including cases and controls \nwho presented to care and received testing (usually at the same facility).\n•Efficient use of resources → allows controls to be selected from same healthcare \nsystem or testing location as cases.\n•Considerations\n•Dependent on sensitivity and specificity of diagnostic testing.\n•Controls positive for another vaccine preventable disease can bias results. \nSensitivity analyses excluding influenza positive controls can be helpful in \nassessing COVID -19 VE.Test-negative design methods\nVaccine effectiveness is a population level estimate.\nAdapted from : https://www.who.int/news -room/feature -stories/detail/vaccine -efficacy -effectiveness -and-protection\n\n01020304050Vaccinated with 2023 -24 COVID -19 vaccine (%)\nWeek end dateAll children\n6m-17y\n12-17y\n5-11y\n6m-4yPercent of adults and children who received 2023-24 COVID-19 vaccine\nNational Immunization Survey-Adult COVID Module (NIS-ACM) and -Child COVID Module (NIS-CCM)\nSeptember 2023-April 2024\nCOVID-19 Vaccination Coverage with 2023-24 Vaccine \nAmong Adults ≥18 Years, NIS -ACMCOVID-19 Vaccination Coverage with 2023-24 Vaccine \nAmong Children 6 Months-17 Years, NIS- CCM\n01020304050Vaccinated with 2023 -24 COVID -19 vaccine (%)\nWeek end dateAll adults\n18+\n75+\n65-74\n50-64\n40-49\n30-39\n18-29\nhttps://www.cdc.gov/vaccines/imz -managers/coverage/covidvaxview/index.html\n•High rates of SARS -CoV-2 infection -induced immunity by July – August 2023.*Context for interpreting COVID-19 VE across age groups\n* Internal CDC data. Data on persons aged ≥16 years is from a longitudinal, national cohort of >35,000 blood donors.\nMethods and prior data available at: https://covid.cdc.gov/covid -data -tracker/#nationwide -blood -donor -seroprevalence -202289%\n89%\n84%\n72%16-29 years\n30-49 years\n50-64 years\n≥65 years\n0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%\nPercent with infection -induced immunityPercent of persons with infection -induced immunity,\nbased on anti -nucleocapsid results from blood donors\nVE findings should be interpreted as the incremental benefit provided by COVID-19 vaccination \nin a population with a high prevalence of vaccine- and infection-induced immunity.\nMeasuring 2023 -2024 COVID-19 VE\nMeasure Definition Vaccinated\ngroupComparison group\nAbsolute VE Compares frequency of health \noutcomes in vaccinated and \nunvaccinated people Received  \nupdated \n(2023 -24) \ndoseReceived no COVID -19 vaccines ever\nRelative VE Compares frequency of health \noutcomes in people who received \none type of vaccine to people who \nreceived a different vaccineReceived  \nupdated \n(2023 -24) \ndoseEligible for, but did not receive, an \nupdated (2023 -24) dose , but received \nprevious doses of COVID -19 vaccine\nVE presented today Compares people who received \n2023 -2024 COVID -19 vaccine to \npeople who did not, regardless of \npast vaccinationReceived  \nupdated \n(2023 -24) \ndoseEligible for, but did not receive, an \nupdated (2023 -24) dose , regardless of \npast vaccination history \nUpdates to COVID -19 VE against symptomatic infection:\nIncreasing Community Access to Testing (ICATT) programMMWR Morb  Mortal Wkly  Rep 2024;73:77 –83. DOI: http://dx.doi.org/10.15585/mmwr.mm7304a2\n\n•Nationwide community -based pharmacy SARS -CoV-2 testing\n•Self-reported COVID -19 vaccination history at time of registration for SARS -CoV-2 testing*\n•Design: Test-negative analysis**\n•Population: Adults ≥18 years with ≥1 COVID -like symptom and nucleic acid amplification testing \n(NAAT) for SARS -CoV-2 \n•Exclusion criteria: Individuals with self -reported immunocompromising conditions, reported a \npositive SARS -CoV-2 test in preceding 90 days***\n•Periods for analysis:\n•Full analysis included tests from September 21, 2023 – May 22, 2024\n•Sub-analysis using S -gene target failure**** included tests from October 27, 2023 – April 3, 2024Increasing Community Access to Testing (ICATT):\nCOVID-19 VE from national pharmacy testing data\n*At 5% of testing encounters, COVID -19 vaccination status is collected by clinician interview. Receipt of 2023 -2024 COVID -19 vac cine formulation determined by date of most recent dose (i.e., after Sept 12, 2023).\n**Odds ratios were calculated using multivariable logistic regression, adjusting for single year of age, gender, race/ethnici ty, SVI of the testing location (<0.5 versus ≥0.5), pharmacy contractor, underlying conditions (presence versus \nabsence), U.S. Department of Health and Human Services region of testing location, and date of testing\n***Additional exclusion criteria: 1) reported receiving Novavax as their most recent dose and reported receiving <2 total COV ID-19 vaccine doses; 2) reported receiving a Janssen (Johnson & Johnson) COVID -19 vaccine dose after May \n12, 2023; 3) received most recent COVID -19 dose <7 days prior to the date of testing or during September 1 -12, 2023; or 4) regis tered for testing with a version of the questionnaire that only reported month and year of the most \nrecent vaccine dose rather than calendar date.\n**** Results of spike gene (S -gene) amplification in real -time reverse transcription –polymerase chain reaction (RT -PCR) can be u sed to distinguish certain SARS -CoV-2 lineages over time (2). S -gene target presence (SGTP) was detected \nin most lineages that circulated in 2023, including XBB lineages, whereas S -gene target failure (SGTF) is detected in JN.1 and o ther BA.2.86 lineages\nLink-Gelles, et al. MMWR 2024: http://dx.doi.org/10.15585/mmwr.mm7304a2  (Results updated with additional data since publication.)\nAge group/2023 -2024 COVID -19 vaccination status/days since \ndoseTotal\ntestsSARS -CoV -2-\ntest -positive, N (%)Median interval since last dose \namong those vaccinated, days \n(IQR) Adjusted VE (95% CI)\n≥18 years\nNo 2023 -2024 COVID -19 dose (ref) 12,965 4,661 (36) 687 (436 to 879) Ref\n2023 -2024 COVID -19 dose , ≥7 days 1,895 483 (25) 70 (38 to 102) 45 (39 to 51)\n2023 -2024 COVID -19 dose , 7-59 days earlier 772 181 (23) 32 (20 to 46) 53 (44 to 61)\n2023 -2024 COVID -19 dose , 60-119 days earlier 809 237 (29) 84 (71 to 97) 34 (22 to 44)\n2023 -2024 COVID -19 dose , 120 -179 days earlier 262 60 (23) 140 (128 to 152) 47 (28 to 60)\n18-49 years\nNo 2023 -2024 COVID -19 dose (ref) 10,395 3,609 (35) 702 (451 to 887) Ref\n2023 -2024 COVID -19 dose , ≥7 days 1,167 272 (23) 69 (39 to 101) 47 (38 to 54)\n2023 -2024 COVID -19 dose , 7-59 days earlier 474 96 (20) 32 (19 to 46) 57 (46 to 66)\n2023 -2024 COVID -19 dose , 60-119 days earlier 507 144 (28) 82 (71 to 95) 31 (15 to 43)\n2023 -2024 COVID -19 dose , 120 -179 days earlier 147 27 (18) 139 (128 to 154) 56 (33 to 72)\n≥50 years\nNo 2023 -2024 COVID -19 dose (ref) 2,570 1,052 (41) 610 (407 to 821) Ref\n2023 -2024 COVID -19 dose , ≥7 days 728 211 (29) 71 (36 to 103) 40 (27 to 50)\n2023 -2024 COVID -19 dose , 7-59 days earlier 298 85 (29) 32 (21 to 44) 44 (26 to 58)\n2023 -2024 COVID -19 dose , 60-119 days earlier 302 93 (31) 85 (73 to 98) 35 (15 to 51)\n2023 -2024 COVID -19 dose , 120 -179 days earlier 115 33 (29) 142 (128 to 152) 30 (-9 to 55)*\n-20 0 20 40 60 80 100ICATT: VE of 2023-2024 COVID-19 vaccine against symptomatic infection \namong adults aged ≥18 years, by age group and time since dose\nSeptember 2023 – May 2024\nLink-Gelles, et al. MMWR 2024: http://dx.doi.org/10.15585/mmwr.mm7304a2  (Results updated with additional data since publication.)\n*Some estimates are imprecise, which might be due to a relatively small number of persons in each level of vaccination or cas e status. This imprecision indicates that the actual VE could \nbe substantially different from the point estimate shown, and estimates should therefore be interpreted with caution. Additio nal data accrual could increase precision and allow more \nprecise interpretation. Ref=referent group; IQR=interquartile range; CI=confidence interval\nTrends in estimated proportions of SARS -CoV-2 S-gene target presence \nand variant proportions in ICATT and Nowcast projections from national\ngenomic surveillance\nSeptember 2023-April 2024 \nS-gene = spike gene; SGTF = S -gene target failure; SGTP = S -gene target presence\nhttps://covid.cdc.gov/covid -data -tracker/#variant -proportions \nOther\nBA.2.86\nJN.1\nJN.1.13\nHK.3\nHV.1FL.1.5.1\nSGT status/2023 -2024 COVID -19 vaccination status/days \nsince doseTotal\ntestsSARS -CoV -2 negative SARS -CoV -2 positive\nAdjusted VE (95% CI) N (row %)Median interval \nsince last dose \namong vaccinated, \ndays (IQR) N (row %)Median interval\nsince last dose \namong vaccinated, \ndays (IQR)\nSGT presence (likely non -JN.1)\nNo 2023 -2024 COVID -19 dose (ref) 2,357 1,934 (69) 668 (410 to 827) 423 (15) 670 (405 to 800) Ref\n2023 -2024 COVID -19 dose , 60-119 days earlier 307 282 (77) 85 (72 to 101) 25 (7) 73 (69 to 83) 58 (33 to 73)\nSGT failure (likely JN.1)\nNo 2023 -2024 COVID -19 dose (ref) 2,366 1,934 (69) 668 (410 to 827) 432 (15) 686 (426 to 829) Ref\n2023 -2024 COVID -19 dose , 60-119 days earlier 343 282 (77) 85 (72 to 101) 61 (17) 89 (75 to 101) 37 (13 to 51)\n0 20 40 60 80 100ICATT: VE of 2023-2024 COVID-19 vaccine against symptomatic infection \namong adults aged ≥18 years, by S -gene target (SGT) presence or failure and \ntime since dose\nOctober 2023 – April 2024\nLink-Gelles, et al. MMWR 2024: http://dx.doi.org/10.15585/mmwr.mm7304a2  (Results updated with additional data since publication.)\nUpdates to COVID -19 VE against COVID- 19-associated \nED/UC encounters :\nVISION and IVY NetworksMMWR Morb  Mortal Wkly  Rep 2024;73:180 –188. DOI: http://dx.doi.org/10.15585/mmwr.mm7308a5  \n\nVISION Multi -Site Network of Electronic Health Records\n369 emergency rooms and urgent cares/229 hospitals \n▪Design: Test-negative analysis\n▪Population: Adults visiting a participating \nemergency department or urgent care (ED/UC) or \nhospitalized with COVID -19-like illness (CLI) with a \nSARS -CoV-2 NAAT test result within 10 days before \nor 72 hours after encounter\n−Cases : CLI with positive  NAAT for SARS -CoV-2 and no \npositive NAAT for RSV or influenza\n–Controls : CLI with negative  NAAT for SARS -CoV-2 and \nno positive NAAT for influenza\n▪Vaccination data: Documented by electronic health records and state and \ncity registries\nAge group/2023 -2024 COVID -19 vaccination status/days since \ndoseTotal\nencountersSARS -CoV -2-\ntest -positive,\nN (%)Median interval\nsince last dose among\nvaccinated among those\nvaccinated, days (IQR) Adjusted VE (95% CI)\n≥18 years\nNo 2023 -2024 COVID -19 dose (ref) 207,695 22,530 (11) 720 (481 -865) Ref\n2023 -2024 COVID -19 dose , ≥7 days 37,809 2,720 (7) 82 (46 -123) 36 (33 -39)\n2023 -2024 COVID -19 dose , 7-59 days earlier 13,144 982 (7) 34 (21 -47) 50 (46 -53)\n2023 -2024 COVID -19 dose , 60-119 days earlier 14,434 1,171 (8) 87 (73 -103) 32 (27 -36)\n2023 -2024 COVID -19 dose , 120 -179 days earlier 10,231 567 (6) 146 (132 -161) 1 (-9-9)\n18-64 years\nNo 2023 -2024 COVID -19 dose (ref) 148,273 15,100 (10) 751 (573 -887) Ref\n2023 -2024 COVID -19 dose , ≥7 days 13,696 819 (6) 78 (42 -119) 38 (33 -43)\n2023 -2024 COVID -19 dose , 7-59 days earlier 5,137 313 (6) 34 (20 -47) 53 (47 -58)\n2023 -2024 COVID -19 dose , 60-119 days earlier 5,186 345 (7) 87 (73 -103) 33 (25 -40)\n2023 -2024 COVID -19 dose , 120 -179 days earlier 3,373 161 (5) 144 (131 -159) -3 (-21-13)\n≥65 years\nNo 2023 -2024 COVID -19 dose (ref) 59,422 7,430 (13) 609 (399 -803) Ref\n2023 -2024 COVID -19 dose , ≥7 days 24,113 1,901 (8) 84 (47 -126) 35 (31 -38)\n2023 -2024 COVID -19 dose , 7-59 days earlier 8,007 669 (8) 35 (21 -47) 47 (42 -51)\n2023 -2024 COVID -19 dose , 60-119 days earlier 9,248 826 (9) 88 (73 -103) 32 (26 -37)\n2023 -2024 COVID -19 dose , 120 -179 days earlier 6,858 406 (6) 146 (133 -162) 7 (-5-17)VISION: VE of 2023-2024 COVID-19 vaccine against ED/UC encounters among \nimmunocompetent adults aged ≥18 years, by age group\nSeptember 2023 – May 2024\n*Some estimates are imprecise, which might be due to a relatively small number of persons in each level of vaccination or case  status. This imprecision indicates that the actual VE could be substantially different \nfrom the point estimate shown, and estimates should therefore be interpreted with caution. Additional data accrual could incr ease precision and allow more precise interpretation.\nhttps://www.cdc.gov/mmwr/volumes/73/wr/mm7308a5.htm  (Results updated with additional data since publication.) VE was calculated as (1 − odds ratio) x 100%, estimated using a tes t-negative case -control \ndesign, with the odds ratio adjusted for age, sex, race and ethnicity, geographic region, and calendar time. -40 -20 0 20 40 60 80 100\nUpdates to COVID -19 VE against COVID-19-associated \nhospitalization and critical illness:\nVISION and IVY NetworksMMWR Morb  Mortal Wkly  Rep 2024;73:180 –188. DOI: http://dx.doi.org/10.15585/mmwr.mm7308a5  \n\nVISION: VE of 2023-2024 COVID-19 vaccine against hospitalization among \nimmunocompetent adults aged ≥18 years, by age group\nSeptember 2023 – May 2024\nAge group/2023 -2024 COVID -19 vaccination status/days \nsince doseTotal\nencountersSARS -CoV -2-\ntest -positive,  N (%)Median interval since last dose\namong those vaccinated,\ndays (IQR) Adjusted VE (95% CI)\n≥18 years\nNo 2023 -2024 COVID -19 dose (ref) 63,908 6,484 (10) 693 (448 -852) Ref\n2023 -2024 COVID -19 dose , ≥7 days 13,195 912 (7) 84 (46 -127) 41 (37 -46)\n2023 -2024 COVID -19 dose , 7-59 days earlier 4,458 345 (8) 34 (20 -47) 49 (43 -55)\n2023 -2024 COVID -19 dose , 60-119 days earlier 4,928 362 (7) 88 (73 -104) 43 (36 -49)\n2023 -2024 COVID -19 dose , 120 -179 days earlier 3,809 205 (5) 146 (133 -162) 14 (0 -27)\n18-64 years\nNo 2023 -2024 COVID -19 dose (ref) 25,209 1,644 (7) 743 (544 -888) Ref\n2023 -2024 COVID -19 dose , ≥7 days 2,363 114 (5) 80 (42 -121) 30 (14 -42)\n2023 -2024 COVID -19 dose , 7-59 days earlier 870 52 (6) 33 (20 -45) 29 (5 -47)\n2023 -2024 COVID -19 dose , 60-119 days earlier 887 43 (5) 88 (74 -103) 35 (11 -53)\n2023 -2024 COVID -19 dose , 120 -179 days earlier 606 19 (3) 146 (134 -160) 15 ( -37-47)*\n≥65 years\nNo 2023 -2024 COVID -19 dose (ref) 38,699 4,840 (13) 651 (419 -827) Ref\n2023 -2024 COVID -19 dose , ≥7 days 10,832 798 (7) 85 (47 -128) 42 (37 -47)\n2023 -2024 COVID -19 dose , 7-59 days earlier 3,588 293 (8) 34 (20 -47) 52 (46 -58)\n2023 -2024 COVID -19 dose , 60-119 days earlier 4,041 319 (8) 88 (73 -104) 43 (35 -49)\n2023 -2024 COVID -19 dose , 120 -179 days earlier 3,203 186 (6) 147 (133 -162) 13 ( -2-26)\n-40 -20 0 20 40 60 80 100*Some estimates are imprecise, which might be due to a relatively small number of persons in each level of vaccination or case  status. This imprecision indicates that the actual VE could be substantially different \nfrom the point estimate shown, and estimates should therefore be interpreted with caution. Additional data accrual could incr ease precision and allow more precise interpretation.\nhttps://www.cdc.gov/mmwr/volumes/73/wr/mm7308a5.htm  (Results updated with additional data since publication.) VE was calculated as (1 − odds ratio) x 100%, estimated using a tes t-negative case -control \ndesign, adjusted for age, sex, race and ethnicity, geographic region, and calendar time.\nVISION: VE of 2023-2024 COVID-19 vaccine against hospitalization among \nadults aged ≥18 years, by immunocompromise status\nSeptember 2023 – May 2024\nImmunocompromise status/2023 -2024 COVID -19 vaccination \nstatus/days since doseTotal\nencountersSARS -CoV -2-\ntest -positive\n N (%)Median interval since \nlast dose among those \nvaccinated, days (IQR) Adjusted VE (95% CI)\n≥18 years, non -immunocompromised\nNo 2023 -2024 COVID -19 dose (ref) 63,908 6,484 (10) 693 (448 -852) Ref\n2023 -2024 COVID -19 dose , ≥7 days 13,195 912 (7) 84 (46 -127) 41 (37 -46)\n2023 -2024 COVID -19 dose , 7-59 days earlier 4,458 345 (8) 34 (20 -47) 49 (43 -55)\n2023 -2024 COVID -19 dose , 60-119 days earlier 4,928 362 (7) 88 (73 -104) 43 (36 -49)\n2023 -2024 COVID -19 dose , 120 -179 days earlier 3,809 205 (5) 146 (133 -162) 14 (0 -27)\n≥18 years, immunocompromised\nNo 2023 -2024 COVID -19 dose (ref) 17,574 1,463 (8) 644 (414 -826) Ref\n2023 -2024 COVID -19 dose , ≥7 days 4,673 289 (6) 84 (46 -127) 28 (18 -38)\n2023 -2024 COVID -19 dose , 7-59 days earlier 1,573 104 (7) 34 (21 -46) 39 (25 -51)\n2023 -2024 COVID -19 dose , 60-119 days earlier 1,753 123 (7) 88 (74 -105) 27 (10 -40)\n2023 -2024 COVID -19 dose , 120 -179 days earlier 1,347 62 (5) 146 (133 -162) 3 (-29-27)*\n-60 -40 -20 0 20 40 60 80 100\nAdditional methods, including definition of immunocompromised available: https://www.cdc.gov/mmwr/volumes/73/wr/mm7308a5.htm  (Results updated with additional data since publication.) VE \nwas calculated as (1 − odds ratio) x 100%, estimated using a test -negative case -control design, adjusted for age, sex, race and ethnicity, geographic region, and calendar time.\n* Some estimates are imprecise, which might be due to a relatively small number of persons in each level of vaccination or ca se status. This imprecision indicates that the actual VE could be \nsubstantially different from the point estimate shown, and estimates should therefore be interpreted with caution. Additional  data accrual could increase precision and allow more precise \ninterpretation. \nVISION: VE of 2023-2024 COVID-19 vaccine against critical illness among \nimmunocompetent adults aged ≥18 years, by age group\nSeptember 2023 – May 2024\nAge group/2023 -2024 COVID -19 vaccination status/days since \ndoseTotal\nencountersSARS -CoV -2-\ntest -positive\n N (%)Median interval\nsince last dose among \nthose vaccinated,\ndays (IQR) Adjusted VE (95% CI)\n≥18 years\nNo 2023 -2024 COVID -19 dose (ref) 58,576 1,152 (2) 694 (452 -855) Ref\n2023 -2024 COVID -19 dose , ≥7 days 12,402 119 (1) 85 (46 -128) 58 (49 -66)\n2023 -2024 COVID -19 dose , 7-59 days earlier 4,151 38 (1) 34 (21 -47) 69 (57 -78)\n2023 -2024 COVID -19 dose , 60-119 days earlier 4,616 50 (1) 88 (74 -104) 57 (43 -68)\n2023 -2024 COVID -19 dose , 120 -179 days earlier 3,635 31 (1) 147 (133 -162) 32 (0 -53)*\n0 20 40 60 80 100\nCDC unpublished data. Critical illness defined as admission to an intensive care unit (ICU) or death while hospitalized or ≤2 8 days after hospital admission. VE was calculated as (1 − odds ratio) x 100%, \nestimated using a test -negative case -control design, adjusted for age, sex, race and ethnicity, geographic region, and calendar time.\n*Some estimates are imprecise, which might be due to a relatively small number of persons in each level of vaccination or cas e status. This imprecision indicates that the actual VE could be \nsubstantially different from the point estimate shown, and estimates should therefore be interpreted with caution. Additional  data accrual could increase precision and allow more precise \ninterpretation.\nIVY Network —26 hospitals, 20 U.S. States\n•Design : Test-negative, case -control design\n•Population : Adults  aged  ≥18 years  hospitalized with COVID -\nlike illness (CLI)* and SARS -CoV-2 test results within 10 days of \nillness onset and 3 days of admission\n–Cases: CLI and test  positive  for SARS -CoV-2 by NAAT or antigen\n–Co-infections with influenza and RSV are excluded\n–Controls : CLI and test negative  for SARS -CoV-2 and influenza by \nRT-PCR\n•Vaccination data: Electronic medical records (EMR), state and \ncity registries, and plausible self -report\n•Specimens: Nasal swabs  obtained on all patients for central \nRT-PCR testing and whole genome sequencing\n*CLI is defined as presence of any one of the following: fever, cough, shortness of breath, chest imaging consistent with pneumoni a, or hypoxemia\n\nIVY: VE of 2023–2024 vaccine against hospitalization among immuno competent  \nadults aged ≥18 years, by age group and time since dose\nSeptember 21, 2023 – April 30, 2024\n*Logistic regression models were adjusted for age, sex, race and ethnicity, geographic region, and calendar time.COVID -19 dosage pattern/age groupCOVID -19 \ncase -patients\nN (Col %)COVID -19 \ncontrol -\npatients\nN (Col %)Median interval\nsince last dose among \nthose vaccinated,\ndays (IQR)VE*\n% (95% CI)\n≥18 years\nNo 2023 -2024 COVID -19 dose (ref) 1538 (89) 4149 (84) 681 (430 –840) Ref\n2023 -2024 COVID -19 dose , ≥7 days 191 (11) 786 (16) 81 (43 –121) 37 (24 –47)\n2023 -2024 COVID -19 dose , 7–89 days earlier 110 (6) 441 (9) 48 (26 -69) 41 (26 –53)\n2023 -2024 COVID -19 dose , 90–179 days earlier 81 (5) 345 (7) 127 (107 –148) 27 (4 –44)\n18–64 years\nNo 2023 -2024 COVID -19 dose (ref) 530 (95) 2084 (90) 733 (485 –879) Ref\n2023 -2024 COVID -19 dose , ≥7 days 27 (5) 236 (10) 73 (34 –112) 52 (26 –68)\n≥65 years\nNo 2023 -2024 COVID -19 dose (ref) 1008 (86) 2065 (79) 643 (406 –802) Ref\n2023 -2024 COVID -19 dose , ≥7 days 164 (14) 550 (21) 82 (45 –123) 35 (20 –47)\n0 20 40 60 80 100\nVaccine  Effectiveness (%)\nIVY*: VE of 2023–2024 vaccine against hospitalization among adults aged \n≥18 years by SARS -CoV-2 lineage using viral whole -genome sequencing\n•Population\n•Cases:  COVID -like illness (CLI) and test positive for SARS -CoV-2†;restricted to patients with sequence -\nconfirmed§JN lineage (BA.2.86 and its descendants)  infection or XBB lineage (all other co -circulating \nlineages) infections\n•Controls: CLI and test negative forSARS -CoV-2 and influenza viruses by RT-PCR\n•Analytic Period: October 18, 2023 –March 9, 2024\n•First date on which a patient was admitted with sequence -confirmed JN lineage infection\n•Last week during which a patient was admitted with sequence -confirmed XBB lineage infection\n•VE¶ against hospitalization was calculated separately using case -patients with sequence -confirmed SARS -\nCoV-2 JN and XBB lineage infections\n* Investigating Respiratory Viruses in the Acutely Ill (IVY) Network. https://www.cdc.gov/flu/vaccines -work/ivy.htm  \n† Case patients who tested positive for influenza viruses or RSV were excluded.\n§ Identification of a SARS -CoV-2 lineage through viral whole -genome sequencing was successful for 63% of case -patients during the  analysis period.\n¶ Odds ratios were adjusted for age, sex, race and ethnicity, geographic region, calendar time, and Charlson comorbidity index.\nIVY: Number of COVID -19 case -patients by hospital admission week and SARS -\nCoV-2 lineage\nOctober 18, 2023 – March 9, 2024\n* Dates are for the end of the admission week. \n† JN lineages comprised BA.2.86 and its descendants. XBB lineages comprised all other co -circulating lineages.\nIdentification of a SARS -CoV-2 lineage through viral whole -genome sequencing was successful for 63% of case -patients during the analysis period.†\nCOVID -19 dosage patternCOVID -19 control -patients COVID -19 case -patients\nVE** (95% CI) N (Col %)Median interval\nsince last dose\namong vaccinated,\ndays (IQR)  N (Col %)Median interval\nsince last dose\namong vaccinated,\ndays (IQR)\nXBB lineages†\nNo 2023 -2024 COVID -19 dose (ref) 3736 (82) 688 (429 –834) 532 (91) 557 (385 –751) Ref\n2023 -2024 COVID -19 dose , 7–89 days earlier 568 (12) 47 (26 –68) 47 (8) 44 (22 –67) 54 (36 –67)\n2023 -2024 COVID -19 dose , 90–179 days earlier 276 (6) 118 (106 –131) 6 (1) 92 (91 –105) §\nJN lineages†\nNo 2023 -2024 COVID -19 dose (ref) 3736 (82) 688 (429 –834) 319 (80) 746 (479 –855) Ref\n2023 -2024 COVID -19 dose , 7–89 days earlier 568 (12) 47 (26 –68) 38 (10) 56 (31 –74) 33 (2 –54)¶\n2023 -2024 COVID -19 dose , 90–179 days earlier 276 (6) 118 (106 –131) 40 (10) 118 (107 –130) 23 (-12 to 48)¶IVY: VE of 2023–2024 COVID -19 vaccine against hospitalization among \nadults aged ≥18 years*, by SARS -CoV-2 lineage and time since dose\nOctober 18, 2023 – March 9, 2024\nCDC unpublished data.* These results include both immunocompetent and immunocompromised persons.\n† JN lineages comprised BA.2.86 and its descendants. XBB lineages comprised all other co -circulating lineages.\n§ Based on timing of recommendations to receive 2023 –2024 COVID -19 vaccines and JN lineage emergence, limited numbers of individu als with XBB infection \nwere 90–179 days from their updated dose, precluding estimation of VE within this stratum.\n¶ Some estimates are imprecise, which might be due to a relatively small number of persons in each level of vaccination or case  status. This imprecision \nindicates that the actual VE could be substantially different from the point estimate shown, and estimates should therefore be i nterpreted with caution.\n** VE estimates adjusted for age, sex, race and ethnicity, geographic region, calendar time, and Charlson comorbidity index.-20 020406080100\nVaccine  Effectiveness (%)\nCOVID -19 VE in young children and\nby age group\nReminder: children aged 6 months -4 years continue to \nbe recommended for a complete initial series\n\nAge group | COVID -19 vaccination statusTotal\nencountersSARS -CoV -2-\ntest -positive, N (%)Median interval since\nlast dose among\nthose vaccinated,\ndays (IQR) Adjusted VE (95% CI)\nNo updated 2023 -2024 COVID -19 vaccine dose*\n9 months -4 years 30,286 1,180 (4) 349 (236 -443) Ref\n5-17 years 37,203 1,449 (4) 650 (449 -769) Ref\n18-64 years 148,273 15,100 (10) 751 (573 -887) Ref\n≥65 years 59,422 7,430 (13) 609 (399 -803) Ref\n2023 -2024 COVID -19 dose received 7 -59 days earlier\n9 months -4 years 613 10 (2) 33 (19 -46) 66 (36 -82)\n5-17 years 805 11 (1) 33 (19 -47) 71 (47 -84)\n18-64 years 5,137 313 (6) 34 (20 -47) 53 (47 -58)\n≥65 years 8,007 669 (8) 35 (21 -47) 47 (42 -51)\n2023 -2024 COVID -19 dose received 60 -179 days earlier\n9 months -4 years 706 14 (2) 104 (80 -137) 24 (-31-56)**\n5-17 years 1,343 22 (2) 111 (86 -138) 50 (22 -68)\n18-64 years 8,559 506 (6) 108 (82 -137) 24 (17 -31)\n≥65 years 16,106 1,232 (8) 111 (84 -142) 25 (20 -30)VISION: VE of 2023–2024 COVID -19 vaccine doses against ED/UC encounters \nwas similar across age groups\nSeptember 2023 – May 2024\n-80-60-40-20 020406080100\n* Includes all individuals who did not receive a 2023 -2024 COVID -19 vaccine. For those aged ≥5 years, this includes unvaccinated  persons and persons who were vaccinated with ≥1 original \nmonovalent or bivalent COVID -19 doses. For those aged <5 years, both those in the referent group and those in the vaccinated gro up were required to have completed an initial series. The 2023 -\n2024 dose could have been part of the initial series or in addition to the initial series.\n** Some estimates are imprecise, which might be due to a relatively small number of persons in each level of vaccination or c ase status. This imprecision indicates that the actual VE could be \nsubstantially different from the point estimate shown, and estimates should therefore be interpreted with caution. Additional  data accrual could increase precision and allow more precise \ninterpretation.\n•2023 -2024 COVID -19 vaccination provided increased protection against symptomatic SARS -\nCoV-2 infection and COVID -19-associated ED/UC visits and hospitalizations compared to no \n2023 -2024 vaccine dose.\n•Waning patterns appeared similar to previous COVID -19 vaccine formulations; most durable \nprotection appeared to be for critical illness, though statistical power was lacking in the \nlongest time period since vaccination\n•As with previous COVID -19 vaccine formulations, effectiveness was similar across age groups\n•Receipt of 2023 -2024 COVID -19 vaccine provided protection against JN.1 and other circulating \nvariants, though may be lower than protection provided against XBB sublineage variants Conclusions \nAcknowledgements \nCDC\nAmadea Britton\nAllison Ciesla\nFatimah Dawood\nJennifer DeCuir\nMonica Dickerson\nKatherine Fleming -Dutra\nSascha Ellington\nShikha Garg\nNathaniel M. Lewis\nKevin Ma\nJosephine Mak\nJoe Miller\nMorgan Najdowski\nErica Okwuazi\nLakshmi Panagiotakopoulos\nZach Smith\nDiya Surie\nCaitlin Ray\nMark Tenforde\nMegan Wallace\nRyan WiegandVISION Collaborators\nWestat\nSarah Bell\nAngela Cheung\nMargaret Dunne\nPatrick Mitchell\nSarah Reese\nElizabeth Rowley\nJanet Watts\nZack Weber\nIntermountain Health\nKristin Dascomb\nKaiser Permanente Center for Health Research\nStephanie A. Irving\nKaiser Permanente Northern California\nNicola P. Klein\nRegenstrief\nShaun J. Grannis\nUniversity of Colorado\nToan C. Ong\nHealthPartners\nMalini B. DeSilva\nColumbia University\nKarthik Natarajan\n+ many more site staff!IVY Collaborators\nCristie  Columbus\nLaurence W. Busse\nSteven Y . Chang\nAbhijit Duggal\nMatthew C. Exline\nManjusha Gaglani\nKevin W. Gibbs\nAdit A. Ginde\nDavid N. Hager\nEstelle S. Harris\nCassandra Johnson\nNicholas J. Johnson\nAkram Khan\nJennie H. Kwon\nAdam S. LauringChristopher Mallow\nEmily Martin\nAmira Mohamed\nNicholas M. Mohr\nJarrod M. Mosier\nIthan  D. Peltan\nMatthew Prekker\nBasmah  Safdar\nWesley H. Self\nNathan I. Shapiro\nJay S. Steingrub\nIvana A. Vaughn\nJennifer G. Wilson\nYuwei Zhu", "summary": "Effectiveness of COVID -19 (2023-2024 Formula)  vaccines  Ruth Link-Gelles, PhD, MPH CDR, US Public Health Service Vaccine Effectiveness Program Lead Coronavirus and Other Respiratory Viruses Division Centers for Disease Control and Prevention  June 27, 2024National Center for Immunization and Respiratory Diseases   •Vaccine effectiveness (VE) methods refresher •Context for interpretation of COVID -19 VE •COVID -19 VE in adults, by outcome and variant: -Symptomatic SARS -CoV-2 -COVID…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/03-COVID-Link-Gelles-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 30}
{"title": "04 COVID Duffy 508", "content": "COVID -19 vaccine safety surveillance \nfor the 2023 -2024 season\nJonathan Duffy, MD, MPH\nImmunization Safety Office\nJune 27, 2024National Center for Emerging and Zoonotic Infectious Diseases\n\n•Vaccine Adverse Event Reporting System (VAERS)\n•V-s afe\n•Vaccine Safety Datalink (VSD)CDC surveillance systems monitoring COVID -19 \nvaccine safety \n2\n•The Vaccine Safety Datalink (VSD) identified two statistical signals for mRNA COVID- 1 9 vaccines \nduring the 2023 -2024 season\n-Guillain -B arré syndrome (GBS) following Pfizer COVID -19 vaccine among people aged ≥65 years\n•An association between mRNA COVID -19 v accines and GBS had not been observed prior to this season \nin VSD or other systems\n•The increased rate ratio observed during the 2023- 2024 season may or may not represent a true risk\n•If ther e is a true risk, it is estimated to be similar to  what is considered acceptable for other adult \nvaccines\n-Ischemic stroke following Moderna (aged ≥65 years) and Pfizer (aged 50 -6 4 years) COVID -19 vaccines\n•The VSD previously observed a statistical signal for ischemic stroke during 2022-2023 for bivalent \nP\nfizer COVID -19 vaccine (aged ≥65 years)\n•Available data do not provide clear and consistent evidence of a safety problem for ischemic stroke wi\nth mRNA COVID -19 vaccines\n•No other new or unexpected safety concerns were identified for the 2023 -2024 C OVID -19 vaccines\n•Any real or theoretical risks of vaccine adverse events need to be placed in the context of the \nb\nenefits of COVID- 19 vaccines in preventing COVID- 19 and its potentially serious complicationsKey points up front\n3\nVaccine Adverse Event Reporting System \n(VAERS)\n5\nVAERS: U.S. reports following COVID -19 vaccination1\nManufacturer Reports\nNAge, \nyears \nMedian (IQR)Sex, \nfemale\nN (%)Non -serious\nN (%)Serious2 \nN (%)Onset interval, \ndays  \nMedian (IQR)\nPfizer 7,215 57 (33– 70) 4,129 (57) 6,781 (94) 434 (6) 0 (0–3)\nModerna 5,954 60 (31– 72) 3,474 (58) 5,502 (92) 457 (8) 0 (0–1)\nNovavax 153 51 (35–70) 86 (56) 140 (92) 13 (8) 1 (0–2)\nUnknown 176 58.5 ( 34–71) 95 (54) 152 (86) 24 (14) 0 (0–1)\nTotal 13,491 59 (32–71) 7,780 (58) 12,568 (93) 923 (7) 0 (0–2)\n1. Reports received during September 12, 2023 – April 19, 2024; reported date of vaccination during September 12, 2023 –  April 1 9, 2024  or missing\n2. Based on the U. S. Code of Federal Regulations (21 CFR 600.80), classification of a serious adverse event includes a repor t of one of the following: \ndeath, life -threatening illness, hospitalization or prolongation of hospitalization, permanent disability, congenital anomaly, o r birth defect. 6\nVAERS: most frequent MedDRA Preferred Terms \nfollowing COVID -19 vaccination by manufacturer \nPfizer Moderna Novavax\nMedDRA PTN=7,215\nn (%)MedDRA PTN=5,954\nn (%)MedDRA PTN=153\nn (%)\nCOVID -19 1899 (26) Fever 743 (13) Headache 21 (13)\nHeadache 485 (7) Fatigue 729 (12) Fever 19 (12)\nFatigue 465 (6) Headache 712 (12) Pain 18 (11)\nFever 407 (6) Pain 546  (9) Pain in extremity 18 (11)\nPain 365 (5) Pain in extremity 502 (8) Fatigue 15 (9)\nReports received during September 12, 2023 – April 19, 2024; reported date of vaccination during September 12, 2023 – April 19, 2024 or missing.\nMedDRA PT = Medical Dictionary for Regulatory Activities Preferred Terms ( https://www.meddra.org ). More than one MedDRA Preferred Term may be \nassigned to a single report.\nPercents represent the number of reports divided by the total number of reports for each vaccine. 7\nV-safe\n•Participants self -e nroll at https://vsafe.cdc.gov\n•Post -v accination surveys\n-Daily during the first week  \n-Weekly through w eek 6\n•Daily surveys solicit adverse events and health impacts after v accination\n-Local  r eactions (e.g., pain, redness, swelling)\n-Systemic reactions (e.g., fatigue, headache, muscle pain)\n-Health impacts (e.g., unable to perform normal daily activities, missed school or \nw\nork, or received medical care)V-safe methods\n9\nV-safe: characteristics of participants with reported \nCOVID -19 vaccination1\nCharacteristicVaccine manufacturer, %\nModerna\nN=4,828Pfizer\nN=4,481Novavax\nN=258Do not know\nN=576Total\nN=10,143\nFemale sex assigned at birth 61.5 61.2 69.4 63.7 61.7\nAge group, years\n 3-17 0.2 0.6 0.8 - 0.4 \n 18-59 26.5 30.8 41.9 34.6 29.3\n ≥60 73.3 68.6 57.4 65.5 70.4\nImmunocompromised 7.7 7.0 8.5 5.0 7.2\nVaccine(s) co -administered 18.3 21.0 14.0 33.0 20.2\n Influenza 8.1 9.9 7.8 17.0 9.4\n RSV 3.5 3.5 2.3 4.9 3.5\n Other 6.7 7.6 3.9 11.1 7.3\n1. For 10,143 V -safe participants aged ≥3 years enrolled in the COVID -19 protocol with ≥1 completed daily survey during Septembe r 11, 2023- May 27, 2024.\n10\nV-safe: percent of people aged ≥3 years who reported reactions and health \nimpacts at least once in days 0 -7 following COVID -19 vaccination, \nby manufacturer\n0.7 0.6 0.4 0.7\n0102030405060708090100\nAny symptoms Injection site\nreactionSystemic reaction Unable to\ncomplete daily\nactivitiesUnable to work or\nattend schoolGot medical carePercent\nModerna Pfizer Novavax Don't know\n11\nVaccine Safety Datalink \n(VSD)\nVaccine Safety Datalink (VSD)\nCollaborative \npr\noject between \nCDC and 13 integrated healthcare organizations\nPopulation of ~1\n3.5 million \npeople annually\n13\n•Sequential monitoring as data become available\n•Monitors a limited set of prespecified outcomes of special interest\n•Designed to detect statistical signals (values above specified statistical \nthresholds)\n•Statistical signals are potential associations and f urther investigation is \nrequired before concluding that a safety concern existsVSD Rapid Cycle Analysis (RCA) surveillance\n14\n•Time period:  September 10, 2023 – April 27, 2024\n•Evaluated the first COVID -19 vaccine dose received during this period\n•Design:  analysis using COVID -19 vaccinated concurrent comparators\n-Compares the outcome incidence among vaccinees in a risk interval with \noutcome incidence on the same day among vaccinees in a comparison interval\n-Adjusted for outcome calendar date, age group, sex, race/ethnicity, VSD site\n•Statistical signal criteria:  \n-The signal threshold is determined from an alpha- spending plan that keeps the \noverall chance of a Type 1 error <0.05 during the surveillance period \n-Supplemental rate ratios with exact 95% confidence intervals VSD RCA methods for the \n2023 -2024 COVID -19 vaccine \n15\nVSD pre -specified outcomes\nAcute disseminated encephalomyelitis (ADEM)\nAcute myocardial infarction\nEncephalitis / myelitis / encephalomyelitis \n(not ADEM or TM)\nGuillain -Barré syndrome (GBS)\nHemorrhagic stroke\nIschemic stroke\nImmune thrombocytopenia\nMyocarditis / pericarditis\nPulmonary embolism\nSeizure\nTransverse myelitis (TM)\n16\nRCA COVID -19 Primary and Supplemental Analyses\nParameters Primary Analyses Supplemental Analyses\nVaccine TypesModerna\nNovavaxPfizerPfizer & Moderna combinedPfizer with fluPfizer with flu high dose/adjuvant Moderna with fluModerna with flu high dose/adjuvant Pfizer without same day vaccinesModerna without same day vaccines\nRisk vs. Comparison Intervals1-21 days vs 43- 63 days\n1-42 days vs 43- 84 daysFor myocarditis/pericarditis: 1-21 days vs 22- 42 days\nAge Groups0-4 y\n5-11 y\n12-17 y\n18-64 y\n≥65 yAllages (≥ 6 months )\n18-49 y\n50-64 y\n60-74 y\n≥75 yFor myocarditis/pericarditis:  12-39 y\n17\nVSD Results\nCOVID -19 vaccine doses administered in VSD\nby manufacturer\n19\nCOVID -19 vaccine doses administered in VSD\nby age group\n20\nCOVID -19 vaccine doses administered in VSD\nwith other vaccines on the same day1\n1 Some people received more than two vaccines on the same day. Not all categories are mutually exclusive.\nFlu=Influenza vaccine; Tdap=Tetanus, Diphtheria, Pertussis vaccine; RSV=Respiratory syncytial virus vaccine; Zoster=Zoster recom binant vaccine; Pneumo =Pneumococcal vaccine 21\nVSD RCA statistical signals\nOutcome Moderna Pfizer\nAcute disseminated encephalomyelitis (ADEM) No No\nAcute myocardial infarction No No\nEncephalitis / myelitis / encephalomyelitis \n(not ADEM or TM)No No\nGuillain -Barré syndrome (GBS) No Yes\nHemorrhagic stroke No No\nIschemic stroke Yes Yes\nImmune thrombocytopenia No No\nMyocarditis / pericarditis No No\nPulmonary embolism No No\nSeizure No No\nTransverse myelitis (TM) No No\n22\nGuillain -Barré syndrome (GBS)\nGuillain- Barré syndrome (GBS) \nVSD statistical signals\nVaccine Moderna Pfizer\nRisk Interval (days) 1 - 21 1 - 42 1 - 21 1 - 42\nAge Group (years)\n0 –4 No No No No\n5 –11 No No No No\n12 –17 No No No No\n18 –64 No No No No\n≥65 No No Yes Yes\n24\nCharacteristics of chart -confirmed GBS cases after \nPfizer COVID -19 vaccine among people aged ≥65 years\nCharacteristicRisk Interval cases \nDays 1 -42\n(n = 7)Comparison Interval cases \nDays 43 -84\n(n = 3)\nBrighton Level1\n1 2 0\n2 5 3\n3 0 0\nAge Group (years)\n65 – 74 4 1\n75 – 84 3 2\n≥85 0 0\nSame day vaccines\nNone 5 2\nAny 2 1\nInfluenza 1 1\nInfluenza + PCV 1 0\n1 Sejvar  et al. Guillain -Barré syndrome and Fisher syndrome: case definitions and guidelines for collection, analysis, and presentation of immunization safety data. Vaccine. 2011;29(3):599 -612 25\nChart -confirmed GBS concurrent comparator analysis for \nPfizer COVID -19 vaccine among people aged ≥65 y ears\nAnalysisCases in \nRisk Interval\n(Days 1 -42)Cases in \nComparison Interval\n(Days 43 -84)Adjusted Rate \nRatio1 \n(95% Confidence \nInterval)\nPfizer, all doses 7 3 4.45 (1.07–  22.62)\nPfizer without same \nday vaccines5 2 4.86 (0.88 – 38.52)\n1 Adjusted for outcome calendar date, age group, sex, race/ethnicity, VSD siteEstimated excess GBS cases:  4.1 per million doses\n26\n•VSD identified a statistical signal for GBS after Pfizer COVID -19 vaccine in adults aged ≥65 years \nduring the 2023- 2024 season\n-The VSD had not identified any signals for GBS with previous mRNA COVID -19 vaccine formulations (i.e., \noriginal primary series, original booster, or 2022 -2023 bivalent) \n-The analysis did not suggest that other vaccines administered on the same day accounted for the \nincreased rate\n•The increased rate ratio observed for Pfizer COVID -19 vaccine during the 2023- 2024 season \nmay or may not represent a true risk, because a large number of  analyses may find some \nassociations by chance alone, and surveillance analyses may have residual confounding\n•There were insufficient doses of Moderna or Novavax vaccines administered in the VSD to \nassess the rate of GBS with those vaccines\n-There is not n ecessarily a difference in GBS rate following Pfizer COVID -19 vaccine and the other COVID -\n19 vaccinesVSD summary and interpretation for GBS\n27\nIschemic stroke\nIschemic stroke \nVSD statistical signals\nVaccine Moderna Pfizer\nRisk Interval (days) 1 - 21 1 - 42 1 - 21 1 - 42\nAge Group (years)\n0 –4 No No No No\n5 –11 No No No No\n12 –17 No No No No\n18 –64 No No Yes No\n≥65 No Yes No No\n29\nIschemic stroke concurrent comparator analysis for\nPfizer  COVID -19 vaccine among people aged 18- 64 years\nAnalysisCases in \nRisk Interval\n(Days 1 -21)Cases in \nComparison Interval\n(Days 43 -63)Adjusted Rate \nRatio1 \n(95% Confidence \nInterval)\nAges 18 -49 13 13 1.12 (0.46 – 2.67)\nAges 50 -64 69 57 1.57 (1.06 – 2.31)\n1 Adjusted for outcome calendar date, age group, sex, race/ethnicity, VSD site 30\n1.57\n1.001.98\n1.48\n1.06\n0.181.070.872.314.97\n3.70\n2.50\n0.001.002.003.004.005.006.00\nPfizer   Moderna3\nVaccine without any \nsame  day vaccinesPfizer     Moderna\nVaccine with or without \nsame day vaccines Pfizer    Moderna3\nVaccine with same day \ninfluenza  vaccineAdjusted Rate Ratio &\n95% Confidence IntervalIschemic stroke supplemental analyses to evaluate statistical signal for \nPfizer  COVID -19 vaccine among people aged  50-64 years\na\nExact Analysis 1 -21 days vs 43- 63 days\nAdjusted Rate Ratios and 95% Confidence Intervals1,2\n1 Dose totals for age group:  Pfizer = 572,885;  Moderna = 57,012\n2 Rate ratios adjusted for outcome calendar date, age group, sex, race/ethnicity, VSD site\n3 This analysis not done for Moderna due to small sample size 31\nIschemic stroke concurrent comparator analysis for \nModerna  COVID -19 vaccine among people aged ≥65  years\nVaccineCases in \nRisk Interval\n(Days 1 -42)Cases in \nComparison Interval\n(Days 43 -84)Adjusted Rate \nRatio1 \n(95% Confidence \nInterval)\nModerna 53 51 1.53 (0.96 – 2.42)\n1 Adjusted for outcome calendar date, age group, sex, race/ethnicity, VSD site 32\nIschemic stroke concurrent comparator analysis for \nmRNA  COVID -19 vaccines among people aged ≥65  years\nVaccineCases in \nRisk Interval\n(Days 1 -42)Cases in \nComparison Interval\n(Days 43 -84)Adjusted Rate \nRatio1 \n(95% Confidence \nInterval)\nModerna 53 51 1.53 (0.96 – 2.42)\nPfizer 574 714 1.00 (0.88 – 1.14)\n1 Adjusted for outcome calendar date, age group, sex, race/ethnicity, VSD site 33\nAdjusted Rate Ratio &\n95% Confidence Interval\nPfizer      Moderna\nVaccine with or without \nsame day vaccines Pfizer       Moderna\nVaccine with same day \ninfluenza  vaccinePfizer Moderna\nVaccine without any \nsame day vaccines1.001.53\n1.042.53\n0.951.26\n0.880.96\n0.831.10\n0.800.701.142.42\n1.295.91\n1.132.24\n0.001.002.003.004.005.006.007.00Ischemic stroke supplemental analyses to evaluate statistical signal for\nModerna  COVID -19 vaccine among people aged ≥65  years\na\nExact Analysis 1 -42 days vs 43- 84 days  \nAdjusted Rate Ratios and 95% Confidence Intervals1,2\n1 Dose totals for age group:  Pfizer = 953,559;  Moderna = 81,553\n2 Rate ratios adjusted for outcome calendar date, age group, sex, race/ethnicity, VSD site 34\n•VSD detected statistical signals for ischemic stroke for Pfizer and Moderna COVID -19 vaccines \nduring the 2023- 2024 season\n-There was a lack of consistent findings across age groups or risk interv als\n-There was not a significantly different risk associated with receipt of simultaneous influenza vaccine\n•The VSD previously identified a statistical signal for ischemic stroke for the 2022 -2023 bivalent \nformulation of Pfizer vaccine in the ≥65 years age group using the 1-21 day  risk interval\n•This season’s findings are consistent with CDC Immunization Safety Office’s prior \ninterpretation based on data review in October 2023 that stated: “Available data do not provide clear and consistent evidence of a safety problem for ischemic stroke with \nbivalent mRNA COVID -19 vaccines when given alone or given simultaneously with influenza \nvaccines”\n1\n•The statistical signals during the 2022 -20232 and the 2023- 2024 seasons require further \nevaluation\n-The VSD has a follow -up retrospective study in progress to further assess the risk of ischemic strokeVSD summary and interpretation for ischemic stroke \n1 Shimabukuro TS, presentation to ACIP, October 25, 2023. Available at: https://www.cdc.gov/vaccines/acip/meetings/downloads/sl ides-2023 -10-25-26/01 -VaxSafety -Shimabukuro -508.pdf\n2 Klein NK, presentation to ACIP, September 12, 2023. Available at: https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2023 -09-12/07 -COVID -Klein -508.pdf 35\nConclusions\n•Rates of local and/or systemic reactions reported by V -safe participants \nduring the first week after receiving a dose of the 2023- 2024 COVID- 19 \nvaccine were similar to  last season\n•VSD identified statistical signals for GBS and ischemic stroke\n•No other new or unexpected safety concerns were identified for the 2023-\n2024 COVID- 19 vaccines by VAERS, V- safe, or VSDConclusions\n37\n•The increased rate ratio of GBS following Pfizer COVID- 19 vaccine among people aged ≥65 years \nobserved during the 2023 -2024 season may or may not represent a true risk\n-If there is a true risk, then t he estimated excess GBS cases of 4.1 per million doses is similar to  \nprevious estimates for other vaccines for adults\n•Influenza:  1 - 2 cases per million doses1\n•Recombinant Zoster Vaccine:  3 - 6 cases per million doses2\n•The VSD statistical signals for ischemic stroke after mRNA COVID- 19 vaccines during the 2023 -2024 \nseason do not provide sufficient evidence to conclude that there is a safety concern. A follow -up VSD \nstudy is in progress to further examine the risk of ischemic stroke after mRNA COVID- 19 vaccines\n•FDA’s 2023- 2024 COVID -19 vaccine safety surveillance using commercial health plans and Medicare \nclaims databases results are expected later this year, which will provide additional information about \nGBS, stroke, and other outcomesConclusions\n381 Perez -Vilar S, et al. Guillain -Barré Syndrome After High -Dose Influenza Vaccine Administration in the United States, 2018 -2019 Season . J Infect Dis. 2021 Feb 13;223(3):416 -425.\n2 Janusz CB, et al. Projected risks and health benefits of vaccination against herpes zoster and related complications in US adults . Human Vaccines & Immunotherapeutics , 18(5), 2022.\n•Any real or theoretical risks of vaccine adverse events need to be placed in \nthe context of the benefits of COVID -19 vaccines in preventing COVID- 19 \nand its potentially serious complications\n•CDC and FDA will continue to monitor the safety of COVID- 19 vaccinesConclusions\n39\nAcknowledgments\n•CDC Immunization Safety Office:\n-Karen Broder, Hannah Brown, Carol Ennulat , Anne Hause, \nTat’Yana Kenigsberg, Paige Marquez, Mike McNeil, Pedro \nMoro, Tanya Myers, Brittney Romanson, David Shay, John Su, Lily Wang, Kimp Walton, Eric Weintraub, Bicheng (Tony) \nZhang\n•Kaiser Permanente Northern California:\n-Ned Lewis, Nicky Klein, Joan Bartlett, Kristin Goddard, Bruce \nFireman, Ousseny Zerbo\n•Marshfield Clinic Research Institute:\n-Jim Donahue, Kayla Hanson, Ed Belongia, Burney Kieke, Dave McClure, Erica Scotty•VSD Sites\n• Denver Health, Denver, Colorado\n• HealthPartners Institute, Minneapolis, Minnesota\n• Kaiser Permanente Colorado, Denver, Colorado\n• Kaiser Permanente Mid Atlantic, Rockville Maryland\n• Kaiser Permanente Northern California, Oakland, California\n• Kaiser Permanente Northwest, Portland, Oregon\n• Kaiser Permanente Southern California, Los Angeles, California\n• Kaiser Permanente Washington, Seattle, Washington\n• Marshfield Clinic Research Institute, Marshfield, Wisconsin\n•FDA Center for Biologics Evaluation and Research, \nOffice of Biostatistics and Pharmacovigilance\n40\nFor more information, contact CDC\n1-800- CDC- INFO (232 -4636)\nTTY:  1 -888- 232- 6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.", "summary": "COVID -19 vaccine safety surveillance  for the 2023 -2024 season Jonathan Duffy, MD, MPH Immunization Safety Office June 27, 2024National Center for Emerging and Zoonotic Infectious Diseases  •Vaccine Adverse Event Reporting System (VAERS) •V-s afe •Vaccine Safety Datalink (VSD)CDC surveillance systems monitoring COVID -19  vaccine safety  2 •The Vaccine Safety Datalink (VSD) identified two statistical signals for mRNA COVID- 1 9 vaccines  during the 2023 -2024 season -Guillain -B arré…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/04-COVID-Duffy-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 41}
{"title": "05 COVID Prosser 508", "content": "Economic analysis of \nCOVID -19 vaccination \nUniversity of Michigan \nCOVID -19 Vaccination Modeling Team \nACIP Meeting \nJune 24, 2024 \n1 \n \n \n \n \n \n      \n Study team \nUniversity of Michigan \n• Lisa A. Prosser, PhD, Principal Investigator \n• David W. Hutton, PhD, Co -Investigator \n• Acham Gebremariam, MS, Programmer/Analyst \n• Angela Rose, MS, MPH, Project Manager \n• Christina Nyamuswa, Research Assistant \nWake Forest University \n• Cara Janusz, PhD Centers for Disease Control and Prevention \n• Jamie Pike, PhD, Health Economist, Project officer \n• Megan Wallace, DrPH, Epidemiologist \n• Ismael Ortega -Sanchez, PhD, Senior Economist \n• Andrew Leidner, PhD, Economist \n• Fangjun Zhou, PhD, Health Scientist \n• Melisa Shah, MD, MPH, Medical Epidemiologist \n• Danielle Moulia, MPH, Health Scientist \n• Ruth Link -Gelles, PhD, Epidemiologist \n• Sharon Saydah, PhD, Epidemiologist \n2 \n    \n Expert panelists – Pediatric Model \nMatthew Daley, MD, University of Colorado School of Medicine \nRachel Gross, MD, New York University Grossman School of Medicine \nSean O’Leary, MD, University of Colorado School of Medicine \nPeter Szilagyi, MD, MPH, University of California, Los Angeles \n3 \n  Conflict of interest statement \nAuthors have no known conflicts of interest. \n4 \n     \n \n   \n  \n \n \n           \n          Objectives \n• Original aims*: \no \no \no \no Estimate annual disease burden and healthcare utilization associated with COVID -19 \nillness and COVID -19 booster vaccination, including cases of symptomatic illness, \nhospitalizations, deaths, adverse events, costs, and quality -adjusted life years \nProject cost -effectiveness of an updated mRNA booster against COVID -19-associated \nillness in persons ages ≥18 years \n• Update s for this Phase 3 model: \nAddition of pediatric age groups: 5 -11y, 12 -17y \nUpdates to adult model to reflect rapidly evolving evidence base \n* Earlier analyses from this model were presented to ACIP in September 2023 and February 2024: Prosser, Lisa A. (2023). Economic Analysis of Vaccination with mRNA \nBooster Dose against COVID -19 Among Adults; Prosser, Lisa A (2024). Economic analysis of an additional dose of COVID -19 vaccine \n5 \n  \n  \n \n \n   \n \n   \n \n   Phase 3 Updates \nPediatric Model -new Adult Model -  revised \n1. Epidemiologic inputs \n2. Seasonality -adjusted vaccine \nimpact \n3. Cost inputs \n4. Quality Adjustments 1.Epidemiologic inputs \n• Hospitalization rates – more recent, lower \n• Probability of Long COVID -stratified by \nillness severity \n2.Cost inputs \n• Costs & productivity losses associated with \nLong COVID -updated \n• Vaccine dose cost -updated to CDC list \nprice \n3.Quality adjustments \n• Symptomatic illness -updated \n6 \nMethods \n7 \nModel \nschematic \nNo ventilator \nVentilator Symptomatic \nCOVID -19 \n(non -hospitalized) \nHospitalized \nCOVID -19 Non -medically \nattended \nOutpatient visit \nNo ICU \nadmission \nICU admission B \nNo \ncomplications \nLong COVID B \nD Death No \nCOVID -19 \nCOVID -19 No Long COVID \nLong COVID \nLong -term \nsequelae No \ncomplications \nLong COVID \nDeath ED visit B \nNo ventilator \nVentilator C \nD C \nUpdated COVID -\n19 vaccination, \n1-dose strategy \nA \nA \nA No updated \nCOVID -19 \nvaccination \nA A \nNo side \neffects \nSystemic \nreaction \nAnaphylaxis \nSevere \nadverse event  \n \n \n  \n  \n \n \n  \n \n  \n \n \n   \n   \nED = emergency department; ICU = intensive care unit 8 \n \n Analysis Plan \n• Project health and economic outcomes stratified by intervention strategy and by \nage subgroups (5 -11y, 12 -17y, 18 -49y, 50 -64y, 65+y) \no Cases \no Hospitalizations \no Deaths \no Costs \no QALYs \no Adverse events \n• Calculate incremental cost -effectiveness ratios comparing updated COVID -19 \nvaccination to no updated vaccination (societal perspective) \n• Conduct base case and uncertainty analyses (one -way sensitivity and scenario \nanalyses) \n9 \n  Model inputs \n10 \n   \n \n \n  \n      Probability of symptomatic illness, annualized \nAge Base case Range for sensitivity analysis Source \nLow High \n5-11 years 0.3145 0.1790 0.4510 Assumption \nbased on adult \ndata* 12-17 years 0.3145 0.1790 0.4510 \n18-49 years 0.3145 0.2858 0.3444 HEROES -\nRECOVER \nDec 2022 -May \n2023 50-64 years 0.2841 0.2438 0.3274 \n65+ years 0.3339 0.2312 0.4510 \n*Base case assumed to be the same as 18 -49 years with a wider range for sensitivity analysis \nUnchanged from Phase 2 11 \n \n                              40 \nWeekly  rates  of \nCOVID- 19 \nassociated  \nhospitalizations  \nby  season,  all  \nages 30 \n20 \n10 Hospitalization rate per 100,000 2021- 2022 \n2020- 2021 \n2022- 2023 \n2019- 2020 \n2023- 2024 \n12 Oct    Nov    Dec  Jan Feb Mar Apr     May    Jun  Jul    Aug Sep \n0 \n \n \n    \n     Probability of hospitalization, annualized \n0.008 0.0079 \n0.007 \n0.006 \n0.005 \n0.004 \n0.003 \n0.002 0.00155 \n0.001 0.000133 0.000181 0.000443 \n0 \n5-11 12-17 18-49 50-64 65+ \nyears years years years years Age Base case Range for sensitivity analysis \nLow High \n5-11 years 0.000133 0.000034 0.000336 \n12-17 years 0.000181 0.000039 0.000456 \n18-49 years 0.000443 0.000101 0.002040 \n50-64 years 0.001550 0.000413 0.004790 \n65+ years 0.007900 0.002450 0.020900 \nSource: Derived using COVID -NET data (October 2022 -September 2023) adjusted by the probability of hospitalization attributable t o COVID -19 by \nquarter. The upper limit is from COVID -NET data (October 2022 -March 2023), unadjusted by the probability of hospitalization attr ibutable to COVID -19. \n13 \n   \n \n  \n   \n         \n       \n \n        \n    Probability and duration of Long COVID, by age \nAge group Initial illness \nseverity Probability of \nLong COVID Range for sensitivity \nanalysis \nLow High Median \nduration \n(months) Source \nSymptomatic 0.002 0.002 0.003 5.8 \nAssumption \n5-17 y Outpatient 0.005 0.003 0.006 7.6 based on adult \nHospitalized 0.008 0.003 0.013 8.9 data* \nSymptomatic 0.011 0.009 0.013 5.8 INSPIRE, \nunpublished data \n18+ y Outpatient \nHospitalized 0.023 \n0.040 0.017 \n0.017 0.029 \n0.064 7.6 \n8.9 Dec 2020 -Mar \n2023. Montoy and \nFord, 2023** \n* Duration assumed to be the same as 18+ y. Probabilities c alibrated to national data from the National Center for Health Statistics \n(Vahratian 2023) \n** Derived using data on extreme fatigue and cognitive difficulties from INSPIRE ( Montoy and Ford 2023, INSPIRE unpublished data) \ncalibrated to national data from the National Center for Health Statistics (Adjaye -Gbewonyo 2023) \n14 \n   \n   \n    \n    \n                                                                             \n0 33 66 99 132 165 198 231 264 297 330 3630 33 66 99 132 165 198 231 264 297 330 363Seasonality-adjusted vaccine impact \nVaccine effectiveness against ED/UC,  5 - 17 y Cases averted 5 -11 y\n3.0 100% \n90% \n2.5 Optimistic 80% \n71% \n70% \n \n \n \n  48% \nBase case Conservative \nHospitalizations per 100,000 Cases averted Cases Vaccine effectiveness \n10% \n0.0 0% 2.0 \n60% \n1.5 50% \n40% \n30% \n20% 1.0 \n0.5 \nOct  Nov   Dec    Jan  Feb    Mar   Apr May Jun Jul Aug  Sep Oct   Nov Dec Jan Feb   Mar   Apr May Jun  Jul Aug Sep \nAge Base case Range for sensitivity analysis Source \nLow High \n5-11 years 0.423 0.133 0.711 VISION \nunpublished data* \n*Sept 2023 -May 2024 \nED = emergency department; UC = urgent care 15 \n    \n \n       \n   \n    \n             \n  Seasonality -adjusted vaccine impact against \nsymptomatic illness/hospitalization \nAge Base case Range for sensitivity analysis Source \nLow High \n5-11 years 0.423 0.133 0.711 VISION, \nAssumption* 12-17 years 0.422 0.136 0.713 \n18-49 years 0.360 0.140 0.475 VISION, IVY , \nseasonality \nadjusted** 50-64 years 0.357 0.141 0.475 \n65+ years 0.347 0.134 0.468 \n* VISION data for Sept 2023 -May 2024, adjusted VE against emergency department/urgent care visits was applied to pediatric age -group \nspecific hospitalization rates from COVID -NET to derive seasonality -adjusted vaccine impact \n** Using data on bivalent booster data from Sep 2022 -May 2023. Range includes minimum and maximum from both data sources, min: \nconservative approach (VE at 180 days=0) and max: optimistic approach (VE at 180 days=VE at 365 days); assumed same VE for sy mptomatic \nillness as hospitalization, seasonality adjusted \n16 \n5-11 years \n35 \n30 \n25 Hospitalizations per 100,000 20 \n15 Base Case Alternative #1 (winter peak) \n10 \nAlternative 2 (spring peak) 5 \n0 Alternative seasonality assumptions – winter, spring peaks \n12-17 years \n35 \n30 25 Hospitalizations per 100,000 20 \n15 \n10 \n5 \n0 \nOct  Nov   Dec   Jan Feb    Mar   Apr May Jun  Jul   Aug  Sep Oct  Nov   Dec   Jan Feb    Mar   Apr May Jun  Jul   Aug  Sep \n0 5 10 15 20 25 30 35 Hospitalizations per 100,000 18-49 years \n0 5 10 15 20 25 30 35 Hospitalizations per 100,000 50-64 years \n0 20 40 60 80 100 120 140 160 180 200 Hospitalizations per 100,000 65+ years \nOct  Nov   Dec   Jan Feb    Mar   Apr May Jun  Jul   Aug  Sep Oct  Nov   Dec   Jan Feb    Mar   Apr May Jun  Jul   Aug  Sep Oct  Nov   Dec   Jan Feb    Mar   Apr May Jun  Jul   Aug  Sep         \n   \n \n             \n                   \n1 2 3 4 5 6 7 8 9 10 11 121 2 3 4 5 6 7 8 9 10 11 12\n1 2 3 4 5 6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 121 2 3 4 5 6 7 8 9 10 11 12\n17 \n  \n  \n  \n   \n    \n                \n              \n  \n  \n \n Vaccination -related costs \n• Direct medical costs of vaccine dose, administration fee, and adverse events \n• Time costs for recipients or caregivers; vary by setting; children ages 5 -11 years most likely to be \nvaccinated in physician office setting \nTable. Vaccine dose cost \nAge Base case Range for sensitivity analysis Source \nLow* High \n5-11 years ** $89 $30 $130 CDC Vaccine \nPrice List 12-17 years** $102 $30 $130 \n18+ years *** $119 $30 $130 \n* Lower bound reflects price of bivalent boosters as of March 2023. \n** Assumes 50% CDC contract pricing and 50% private sector pricing \n***Assumes 12.8% receive vaccines through government programs (Source: CDC unpublished data) \nNote: Age 12+ private sector/CDC contract prices: Moderna $ 128/$85.91; Novavax $130/$58; Pfizer $115/$97.75 \nAge 5 -11 private sector/CDC contract prices: Moderna $ 128/$85.91; Pfizer $77/$65.45 \nCosting year: 2023 \n18 \n    \n  \n Direct medical costs (supplementary slides) \n• Vaccination -related adverse events \n• OTC & prescription medications for medically -attended non -\nhospitalized illness \n• Outpatient visit (claims data) \n• Emergency department visit \n• Hospitalizations with and without complications (ventilator \nassistance, ICU stay) \n• Long COVID – pediatric estimates based on adult data \nOTC = over the counter medications; ICU = intensive care unit \n19 \n   \n \n  Time costs/productivity losses* \n(supplementary slides) \n• Vaccination receipt \n• Vaccination -related adverse events \n• Outpatient visit \n• Emergency department visit \n• Hospitalizations with and without complications (ventilator \nassistance, ICU stay) \n• Long COVID \n• Deaths \n*Caregiver time costs or productivity losses for pediatric age groups \nICU = intensive care unit \n20 \n     \n  \n  \n \n \n  \n \n  \n \n \n    QALYs lost, COVID -19 illness & hospitalization \nRange for Sensitivity Analysis Age Base Case Low High \nSymptomatic illness \n5-17 years 0.0057 0.0030 0.0085 \n18+ years 0.0046 0.0018 0.0074 \nHospitalization, no ICU stay \n5-17 years 0.0189 0.0054 0.0325 \n18+ years 0.0174 0.0038 0.0310 \nHospitalization, with ICU stay, ventilator assistance \n5-17 years 0.0883 0.0632 0.1169 \n18+ years 0.0394 0.0231 0.0583 \nICU = intensive care unit; QALD = quality -adjusted life day; QALY = quality -adjusted life year QALD \n2.1 \n(1.1 – 3.1) \n1.7 \n(0.7 – 2.7) \n6.9 \n(2.0 – 11.9) \n6.4 \n(1.4 – 11.3) \n32.2 \n(23.1 – 42.7) \n14.4 \n(8.5 – 21.3) Source \nSoare 2023 \nSoare 2023 \nMercon 2023 \n21 \nResults \n22 \n    \n \n   \n       \n   \n       \n    \n       \n    \n         \n   \n         Disaggregated results, per 100,000 people, \npreliminary estimates \nAge \ngroup Strategy Health outcomes Health outcomes averted \nCases Long \nCOVID Hosp ICU Deaths Cases Long \nCOVID Hosp ICU Deaths \n5-11 y No updated vax 31,450 71 13.3 2.7 0.12 - - - - -\nUpdated Covid -19 vax, 1 -dose 18,147 41 7.7 1.6 0.07 13,303 30 5.6 1.2 0.05 \n12-17 y No updated vax 31,450 72 18.1 3.8 0.12 - - - - -\nUpdated Covid -19 vax, 1 -dose 18,178 41 10.5 2.2 0.07 13,272 30 7.6 1.6 0.05 \n18-49 y No updated vax 31,450 413 44.3 5.8 0.59 - - - - -\nUpdated Covid -19 vax, 1 -dose 20,128 265 28.4 3.1 0.32 11,322 149 15.9 2.7 0.26 \n50-64y No updated vax 28,410 396 155.0 29.9 4.99 - - - - -\nUpdated Covid -19 vax, 1 -dose 18,268 255 99.7 16.2 2.80 10,142 142 55.3 13.7 2.19 \n65+ y No updated vax 33,390 501 790.0 105.9 40.06 - - - - -\nUpdated Covid -19 vax, 1 -dose 21,804 327 515.9 58.1 23.47 11,586 174 274.1 47.7 16.59 \nHosp = hospitalizations; ICU = intensive care unit stays \n23 \n                                              \n0 10,000 20,000 30,000 40,000 50,000 \n5-11 y 12-17 y 18-49 y 50-64y 65+ y COVID-19 cases \n0 200 400 600 800 1000 \n5-11 y 12-17 y 18-49 y 50-64y 65+ y Long COVID Cases 1000 Hospitalizations \n800 \n600 \n400 \n200 \n0     \n Disaggregated results, per 100,000 people, \npreliminary estimates \n5-11 y 12-17 y 18-49 y 50-64y 65+ y \n150 ICU stays \n120 \n90 \n60 \n30 \nICU = intensive care unit \n0 24 \n5-11 y 12-17 y 18-49 y 50-64y 65+ y 0 30 60 90 120 150 \n5-11 y 12-17 y 18-49 y 50-64y 65+ y Deaths \n\n   \n    \n \n  \n \n \n \n \n \n \n \n \n Incremental cost -effectiveness ratios, \nsocietal perspective, per 1000 people, \npreliminary estimates \nAge \ngroup Strategy Projected \nCosts Incremental \nCosts Projected \nQALYs Incremental \nQALYs $/QALY \n5-11 y No updated vax $38,124 - 26,788 - -\nUpdated Covid -19 vax, 1 -dose $188,339 $150,215 26,789 0.7494 $200,445 \n12-17 y No updated vax $45,219 - 24,638 - -\nUpdated Covid -19 vax, 1 -dose $198,613 $153,394 24,639 0.7570 $202,621 \n18-49 y No updated vax $131,991 - 20,208 - -\nUpdated Covid -19 vax, 1 -dose $261,080 $129,089 20,209 0.6083 $212,225 \n50-64y No updated vax $237,902 - 12,278 - -\nUpdated Covid -19 vax, 1 -dose $326,508 $88,606 12,279 0.7824 $113,248 \n65+ y No updated vax $363,304 - 6,525 - -\nUpdated Covid -19 vax, 1 -dose $403,428 $40,124 6,527 1.7215 $23,308 \nQALY = quality -adjusted life year \n25 \n \n \n \n Incremental  cost-effectiveness  ratios, \npreliminary  estimates \nAge group Societal perspective \n$/QALY \n5-11 y $200,445 \n12-17 y $202,621 \n18-49 y $212,225 \n50-64y $113,248 \n65+ y $23,308 \nQALY = quality -adjusted life year \n26 \n \n \n  \n \n   \n   \n   \n  \n    \n         \n \n    \n One way sensitivity analyses, 5 -11 y \npreliminary estimates \nVaccine impact, symptomatic illnes/hospitalization(0.711, 0.133) \nQALYs lost, symptomatic COVID-19 (0.009, 0.003) \nProbability, symptomatic COVID-19 (0.451, 0.179) \nCost, vaccine dose ($30, $130) \nTime (h) spent to receive vaccine (0.170, 2) \nProbability, hospitalization given symptomatic COVID-19 (0.00003, 0.00034) \nCost, vaccine administration per dose ($20.30, $28.90) \nQALYs lost, systemic reaction (0.0001, 0.0004) \nTime (h) spend to receive vaccine, pharmacy (0.083, 0.500) \nProportion, patients with productivity loss due to Long COVID (1, 0.250) \n0 100,000 200,000 300,000 400,000 500,000 600,000 700,000 \n$/QALY \nBase case: $200,445 \nNote: Numbers in parentheses indicate input values for sensitivity analysis \nQALY = quality -adjusted life year 27 \n \n \n \n   \n  \n \n  \n   \n \n         \n \n    \n One way sensitivity analyses, 18 -49 y \npreliminary estimates \nVaccine impact, symptomatic illness/hospitalization (0.475, 0.140) \nQALYs lost, symptomatic COVID-19 (0.007, 0.002) \nCost, vaccine dose ($30, $130) \nProbability, hospitalization given symptomatic COVID-19 (0.0020, 0.0001) \nProbability, symptomatic COVID-19 (0.344, 0.286) \nProductivity loss, Long COVID (1, 0.250) \nProbability, systemic reaction (0.073, 0.148) \nTime (h) spent to receive vaccine (0.170, 2) \nVaccine impact, critical illness/death (0.664, 0.287) \nProportion, patients with productivity loss due to Long COVID (1, 0.250) \n 100,000 200,000 0 300,000 400,000 500,000 600,000 700,000 \n$/QALY \nBase case: $212,225 \nNote: Numbers in parentheses indicate input values for sensitivity analysis \nQALY = quality -adjusted life year 28 \n     \n \n \n \n \n \n \n \n       \n           \n   Scenario analysis: probability of symptomatic illness*, \nICER ($/QALY) \npreliminary estimates \nAge group Base case** \n0.1 Probability of symptomatic illness \n0.2 0.3 0.4 0.5 \n5-11 y $200,445 $722,624 $331,876 $211,334 $152,732 $118,088 \n12-17 y $202,621 $714,398 $334,103 $213,584 $154,431 $119,286 \n18-49 y $212,225 $709,386 $356,815 $224,808 $155,707 $113,199 \n50-64 y $113,248 $264,675 $162,297 $106,065 $70,517 $46,014 \n65+ y $23,308 $48,896 $36,178 $26,213 $18,195 $11,603 \n*One -way sensitivity analysis of non -hospitalized symptomatic illness varied separately from hospitalization and critical illnes s \n**Base case probability of symptomatic illness: 5 -49 y: 0.3145; 50 -64 y: 0.2841; 65+ y: 0.3339 \nICER = incremental cost-effectiveness ratio; QALY=Quality -adjusted life year \n29 \n    \n \n \n \n \n \n \n \n          \n \n        \n             \n   Scenario analysis: probability of hospitalization, \nICER ($/QALY) \npreliminary estimates \nAge group Base case* Probability of hospitalization** \n¼ base case ½ base case 2x base case 3x base case 4x base case \n5-11 y $200,445 $206,836 $204,683 $192,231 $184,349 $176,779 \n12-17 y $202,621 $210,339 $207,740 $192,689 $183,146 $173,970 \n18-49 y $212,225 $243,483 $232,548 $176,831 $147,052 $121,649 \n50-64 y $113,248 $214,304 $173,146 $41,319 Cost saving Cost saving \n65+ y $23,308 $133,631 $78,440 Cost saving Cost saving Cost saving \n*Base case probability of h ospitalization: 5-11 years: 0 .000133; 12-17 years: 0.000181; 18 -49 years: 0.000443; 50 -64 years: 0.001550; 65+ \nyears 0.007900 \n**Adjusted risk of hospitalization by underlying condition: chronic obstructive pulmonary disease: 0.9, history of stroke: 0. 9, coronary artery \ndisease: 1.3, asthma: 1.4, hypertension: 2.8, obesity: 2.9, diabetes: 3.2, chronic kidney disease: 4.0, severe obesity: 4.4. Ko et al 2021. \nICER = incremental cost-effectiveness ratio; QALY = Quality -adjusted life year \n30 \n       \n \n \n \n  \n \n  \n \n \n  \n     Scenario analysis: All Long COVID submodel parameters*, \nICER ($/QALY) \npreliminary estimates \nAge group Base case Long COVID submodel parameters \nAll low All high \n5-11 y $200,445 $206,021 $188,365 \n12-17 y $202,621 $208,341 $190,416 \n18-49 y $212,225 $247,483 $160,934 \n50-64 y $113,248 $139,203 $74,095 \n65+ y $23,308 $28,118 $15,148 \n*Long COVID probabilities, costs, productivity losses and quality adjustments varied simultaneously \nICER = incremental cost-effectiveness ratio; QALY = Quality -adjusted life year \n31 \n     \n \n     \n \n  \n \n \n Vaccine impact scenario analysis, ICER ($/QALY), \npreliminary estimates \nBase case Scenario 1 \nAll lower bounds Scenario 2 \nAll upper bounds \n5-11 y $200,445 $780,660 $108,061 \n12-17 y $202,621 $750,981 $107,709 \n18-49 y $212,225 $672,057 $138,503 \n50-64 y $113,248 $396,767 $52,024 \n65+ y $23,308 $141,215 Cost saving \nQALY = quality -adjusted life year \n32 \n     \n \n \n  \n \n  \n \n \n   Scenario analysis: alternative seasonality scenarios, \nICER ($/QALY), \npreliminary estimates \nBase case Alternative seasonality \nscenario #1 \nwinter peak Alternative seasonality \nscenario #2 \nspring peak \n5-11 y $200,445 $229,108 $226,324 \n12-17 y $202,621 $230,316 $228,911 \n18-49 y $212,225 $264,075 $296,491 \n50-64 y $113,248 $135,556 $168,275 \n65+ y $23,308 $27,392 $42,660 \nICER = incremental cost-effectiveness ratio; QALY = quality -adjusted life year \n33 \n       \n \n  \n  \n \n \n      \n   Scenario analysis: vaccine dose cost, ICER ($/QALY), \npreliminary estimates \nAge group Base case* Vaccine dose cost \n$30 $50 $70 $90 $110 $130 \n5-11 y $200,445 $121,596 $148,284 $174,971 $201,659 $228,347 $255,035 \n12-17 y $202,621 $106,933 $133,352 $159,770 $186,188 $212,607 $239,025 \n18-49 y $212,225 $66,351 $99,231 $132,112 $164,992 $197,873 $230,753 \n50-64 y $113,248 Cost saving $25,403 $50,965 $76,528 $102,090 $127,652 \n65+ y $23,308 Cost saving Cost saving Cost saving $6,618 $18,236 $29,854 \n*Base case vaccine cost: 5 -11 y: $89.09; 12 -17 y: $102.44; 18+ y: $118.73 \nICER = incremental cost-effectiveness ratio; QALY = quality -adjusted life year \n34 \n   \n \n \n  \n \n  \n \n \n     \n   Multi -way sensitivity analysis: vaccination -related costs, \nICER ($/QALY) \npreliminary estimates \nAge group Base case Vaccination -related costs* \nAll low All high \n5-11 y $200,445 $88,225 $292,895 \n12-17 y $202,621 $79,777 $271,786 \n18-49 y $212,225 $39,518 $267,101 \n50-64 y $113,248 Cost saving $155,887 \n65+ y $23,308 Cost saving $43,137 \n*Vaccination related and adverse event related costs and productivity losses varied simultaneously \nICER = incremental cost-effectiveness ratio; QALY = Quality -adjusted life year \n35 \n  \n \n  \n \n \n  \n Limitations \n• Data sources vary in representativeness, generalizability \n• Unpublished data used to derive key parameters in the model: vaccine impact, \nsymptomatic illness, probabilities of hospitalization and critical illness \n• VE estimates derived from a single season \n• Few seasons to date to estimate seasonality \n• Model does not include reduced transmission (conservative approach) \n• Claims data used to estimate costs includes only supplemental insurance for 65+ \n• Evidence base for Long COVID is especially scarce, even more so for pediatric age \ngroups \n• Rapidly evolving evidence base; as critical illness attributable to COVID -19 illness \ndeclines, mild/moderate illness and Long COVID could become primary drivers of \ncost-effectiveness \n36 \n   \n    \n  \n \n  \n   \n  \n    \n  \n  \n  \n  \n  Summary -preliminary estimates \n➢Vaccination averts morbidity and mortality for all age groups, but with substantial variation in \nimpact by age \n➢Adult age groups \n• Phase 3 model projects somewhat less  favorable results overall due to declining burden of illness \n• ICERs for 65+ age group [$23,000/QALY] are robust to changes in parameter inputs across plausible \nranges [cost saving -$117,000/QALY] \n• ICERs for 18 -49y [$212,000/QALY] and 50 -64y [$113,000/QALY] age groups are sensitive to changes in \nparameter inputs Parameter Age ICER range ($/QALY) \nVaccine impact 18-49 y $145,000 – $616,000 \n50-64 y $68,000 – $296,000 \nQOL impact, symptomatic illness 18-49 y $140,000 – $443,000 \n50-64 y $83,000 – $178,000 \nVaccine dose cost 18-49 y $66,000 – $231,000 \n50-64 y cost saving – $128,000 \nRisk of hospitalization 18-49 y $108,000 – $244,000 \n50-64 y cost saving – $211,000 \n37 \n    \n \n \n  \n       \n   \n    \n   \n   \n   \n  \n   Summary -preliminary estimates (2) \n➢Pediatric age groups \n• ICERs for 5 -11y [$200,000/QALY] and 12 -17y [$203,000/QALY] age groups are very sensitive to \nchanges in parameter inputs \nParameter Age ICER range ($/QALY) \nVaccine impact 5 -11 y $110,000 -$743,000 \n12 -17 y $109,000 -$720,000 \nQOL impact, symptomatic illness 5 -11 y $134,000 -$385,000 \n12 -17 y $136,000 -$385,000 \nProbability, symptomatic illness 5 -11 y $133,000 -$375,000 \n12 -17 y $135,000 -$377,000 \nVaccine dose cost 5 -11 y $107,000 -$239,000 \n12 -17 y $107,000 -$239,000 \n• Evidence base for pediatric age groups overall less robust \n• Estimated results reflect higher degree of uncertainty compared with adult age groups \n38", "summary": "Economic analysis of  COVID -19 vaccination  University of Michigan  COVID -19 Vaccination Modeling Team  ACIP Meeting  June 24, 2024  1                    Study team  University of Michigan  • Lisa A. Prosser, PhD, Principal Investigator  • David W. Hutton, PhD, Co -Investigator  • Acham Gebremariam, MS, Programmer/Analyst  • Angela Rose, MS, MPH, Project Manager  • Christina Nyamuswa, Research Assistant  Wake Forest University  • Cara Janusz, PhD Centers for Disease Control and Prevention  •…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/05-COVID-Prosser-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 38}
{"title": "06 COVID Panagiotakopoulos 508", "content": "National Center  for Immunization and Respiratory Diseases \nEvidence to Recommendations Framework: \n2024 -2025 COVID -19 Vaccines in Persons ≥6 Months of Age \nLakshmi Panagiotakopoulos, MD, MPH \nACIP Meeting \nJune 27, 2024 \n\n \n    \n \n Evidence to Recommendations (EtR) Framework \nPolicy Question \n• Should 2024 – 2025 COVID -19 vaccines be recommended for use in persons \n≥6 months of age? \n• Products and ages under review for authorization or approval by FDA \ninclude: \n-Moderna COVID -19 vaccine for ages 6 months and older \n-Novavax COVID -19 vaccine for ages 12 years and older \n-Pfizer -BioNTech COVID -19 vaccine for ages 6 months and older \nFDA: Food and Drug Administration 2 \nEtR Domain: \nPublic Health Problem \n   \n     \n Weekly population -based rates of COVID -19-associated hospitalizations, \nby age group — COVID -NET, May 6, 2023 – May 11, 2024 Rate per 100,000 population 70 \n60 \n50 \n40 \n30 \n20 \n10 \n0 \nWeek Ending Date \n<6 months 6 months –4 years 5–11 years 12–17 years \n18–49 years 50–64 years 65–74 years ≥75 years \nCDC COVID Data Tracker. https://covid.cdc.gov/covid -data -tracker/#covidnet -hospitalization -network . Accessed June 17, 2024 4 \n   \n                 \n \n      \n    Monthly rates of COVID -19-associated deaths by age group, \nUnited States, May 1, 2023 – April 30, 2024 \nAge Group \nProvisional data are non -final counts of deaths based on reported mortality data in NVSS. Deaths include those with COVID -19, co ded as ICD –10 code U07.1, on the death certificate. Death data are displayed by date \nof death (event). \nSource: Provisional data from the CDC’s National Center for Health Statistics (NCHS) National Vital Statistic System (NVSS); CDC COVID Data Tracker. https://covid.cdc.gov/covid -data -\ntracker/#demographicsovertime . Accessed June 16, 2024 5 \n \n       \n      \n  \n     Weekly number of COVID -19-associated deaths reported to \nCDC, United States, June 3, 2023 – June 8, 2024 \nThe most recent 3 weeks of mortality counts are shaded grey because NVSS reporting is <95% during this period. \nProvisional data are non -final counts of deaths based on reported mortality data in NVSS. Deaths include those with COVID -19, co ded as ICD –10 code U07.1, on the death certificate. Death data are displayed by date of \ndeath (event). Data include underlying and contributing causes of death. \nCDC COVID Data Tracker. National Center for Health Statistics (NCHS) National Vital Statistics System (NVSS ). https://covid.cdc.gov/covid -data -tracker/#trends_weeklydeaths_select_00 . Accessed June 17, 2024 6 \nTotal number of COVID -19-associated deaths1,2 in 2023, by age group, \nUnited States \n50000 \n44,05945000 \n58 44 81 819 4815 \n0 5000 10000 15000 20000 25000 30000 35000 40000 Number of Deaths \n1 \n    \n< 1 year 1-4 years 5-19 years 20-44 years 45-64 years ≥65 years \n1  \n \n   \n         \n      \n       Provisional data \n2 Underlying cause of death \nSource: Centers for Disease Control and Prevention, National Center for Health Statistics. National Vital Statistics System, Provisional Mortality on CDC WONDER Online Database. Data are from the final Multiple Cause of \nDeath Files, 2018 -2022, and from provisional data for years 2023 -2024, as compiled from data provided by the 57 vital statistics jurisdictions through the Vital Statistics Cooperative Program. Number of deaths includes COVID -\n19 code (U07.1) as the underlying cause of death. Accessed at http://wonder.cdc.gov/mcd -icd10 -provisional.html on June 5, 2024 7 \n  \n \n \n   \n         \n       \n          \n                Total number of COVID -19 and Influenza -associated deaths1,2 in 2023, \nby age group, United States \n90 81 \n58 \n44 \n17 39 71 \n0 10 20 30 40 50 60 70 80 Number of Deaths \n1 \n< 1 year 1-4 years 5-19 years\nCOVID-19 Influenza \n1 Provisional data \n2 Underlying cause of death \nSource: Centers for Disease Control and Prevention, National Center for Health Statistics. National Vital Statistics System, Provisional Mortality on CDC WONDER Online Database. Data are from the final Multiple Cause of \nDeath Files, 2018 -2022, and from provisional data for years 2023 -2024, as compiled from data provided by the 57 vital statistics jurisdictions through the Vital Statistics Cooperative Program. Number of deaths includes \ninfluenza codes (J09 -J11) or COVID -19 code (U07.1) as the underlying cause of death. Accessed at http://wonder.cdc.gov/mcd -icd10 -provisional.html on June 5, 2024 \nNote: Estimates of pediatric influenza deaths reported to CDC can be found here: https://www.cdc.gov/flu/weekly/index.htm . Estimates will vary due to differences in reporting methods and timeframes used. 8 \n \n  \n \n \n  \n  \n  \n  \n    Variant Predominant Period Dates Number of MIS-C Incidence per 1,000,000 Median \nCases person -months (95% CI) Age (IQR), \nyears \nPre-Delta Oct 15, 2020 –Apr 5, 2021 3,284 6.79 (6.56 –7.03) 9.2 (5.4 –13.1 ) \nDelta Jul 10 –Dec 24, 2021 2,300 4.90 (4.70 –5.10) 9.1 (5.5 –12.3) \nOmicron BA.1/BA 1.1 Jan 1 –Ap 8, 2022 1,149 4.21 (3.98 –4.46) 7.5 (4.1 –11.5) \nOmicron BA.2/BA.4/BA.5 April 9 –Dec 31, 2022 422 0.56 (0.51 –0.62) 5.4 (2.8 –9.8) \n2023 Omicron subvariants Jan 1 –Dec 31, 2023 117 0.11 (0.10 –0.14) 6.9 (3.4 –11.5) \nCases from 2023 were clinically similar to those with MIS -C illness onset in 2021 -2022 \n58% were previously healthy with no underlying medical conditions \n50% required ICU -level care, 34% had shock, and 27% had cardiac dysfunction \n3 deaths \nMISC: Multisystem Inflammatory Syndrome in Children 9 \n▪ Incidence by SARS- CoV-2 variant-predominant periods, defined using surveillance data and allowing  \nfor 2 weeks to MIS-C onset from when a variant exceeded 50%  circulating lineages \n \n      \n Underlying Medical Conditions among Patients \nAdmitted to ICU among Children and Adolescents Ages \n≤17 Years with COVID -19-associated Hospitalization, \nJuly 2023 –March 2024 \nAge category Among all \nhospitalized \nchildren, % with \nno underlying \nconditions Among those \nadmitted to ICU, % \nwith no underlying \nconditions \n(n=363) \nOverall ≤17 Years 50% 40% Among those with no \nunderlying conditions, \nwhat % were admitted \nto ICU? \n(n=791) \n18% \nHospitalizations are limited to those with COVID -19 as the presenting complaint upon admission. 10 \n \n  \n \n \n \n  \n      \n      \n     \n                 \n         \n          Other pediatric vaccine preventable diseases: Annual hospitalizations \nper 100,000 population prior to vaccine recommendation compared \nto COVID -19 \nHepatitis A1 Varicella2 \n(Chickenpox) Vaccine -type \nInvasive \nPneumococcal \nDisease3 COVID -194 \nAge 5–14 years 0–4 years 0–4 years 6 months –<18 years \nTime period 2005 1993 –1995 1998 –1999 2022 –2023 2023 –2024 \nHospitalization \nBurden \n(Annual rate per \n100,000 population) <1 29-42 405 6 months – \n4 years: 74 \n5–11 years : 17 \n12–17 years: 24 6 months – \n4 years: 50  \n5–11 years : 10 \n12–17 years: 13 \n1 https://www.cdc.gov/mmwr/preview/mmwrhtml/ss5603a1.htm \n2Davis MM, Patel MS, Gebremariam A. Decline in varicella -related hospitalizations and expenditures for children and adults after introduction of varicella vacci ne in the United States. Pediatrics. 2004;114(3):786 -792. \ndoi:10.1542/peds.2004 -0012 \n3 Centers for Disease Control and Prevention (CDC). Direct and indirect effects of routine vaccination of children with 7 -valent pneumococcal conjugate vaccine on incidence of invasive pneumococcal disease --United \nStates, 1998 -2003. MMWR Morb Mortal Wkly Rep. 2005 Sep 16;54(36):893 -7. PMID: 16163262. \n4 COVID -NET data October 2022 – September 2023 and October 2023 – May 2024. COVID -19 rates have not been adjusted for reason for admission. COVID vaccine first introduced in 12 -17 years in May 2021; in 5 -11 \nyears in November 2021 and in 6 months – 4 years in June 2022 \n5 Vaccine -type invasive pneumococcal disease annual rate for children <5 years in 1998 -1999 was 80 per 100,000, of which about 50% were hospitalized. 11 \n \n  \n \n \n \n      \n           \n         \n        \n             \n                Pediatric vaccine preventable diseases: Deaths per year in the United \nStates prior to vaccine recommendation compared to COVID -19 \nHepatitis A1 Meningococcal \n(ACWY)2 Varicella3 Rubella4 Rotavirus5 COVID -196 \nAge <20 years 11–18 years 5–9 years All ages <5 years 6 months –19 years \nTime \nperiod 1990 –1995 2000 –2004 1990 –1994 1966 –1968 1985 –1991 2023 \nAverage \ndeaths \nper year 3 8 16 17 20 1–4 years : 44 \n5–19 years: 81 \n1Vogt TM , Wise ME, Bell BP, Finelli L. Declining hepatitis A mortality in the United States during the era of hepatitis A vac cination. J Infect Dis2008; 197:1282 –8. \n2National Notifiable Diseases Surveillance System with additional serogroup and outcome data from Enhanced Meningococcal Disea se Surveillance for 2015 -2019. \n3Meyer PA, Seward JF, Jumaan AO, Wharton M. Varicella mortality: trends before vaccine licensure in the United States, 1970 -1994. J Infect Dis. 2000;182(2): 383-390. doi:10.1086/315714 \n4Roush SW , Murphy TV; Historical comparisons of morbidity and mortality for vaccine -preventable diseases in the United States. J AMA 2007; 298:2155 –63. \n5 Glass RI, Kilgore PE, Holman RC, et al. The epidemiology of rotavirus diarrhea in the United States: surveillance and estimat es of disease burden. J Infect Dis. 1996 Sep;174 Suppl 1:S5 -11 \n6 http://wonder.cdc.gov/mcd -icd10 -provisional.html on May 14 2024 . COVID vaccine first introduced in 12 -17 years in May 2021; in 5 -11 years in November 2021 and in 6 months – 4 years in June 2022 12 \nDomain Equity Question: \nDoes the problem impact all populations equally? \n      Age-adjusted cumulative COVID -19 hospitalizations per 100,000 population \nby race and ethnicity — COVID -NET, October 2023 – May 2024 \nCDC COVID Data Tracker. https://covid.cdc.gov/covid -data -tracker/#covidnet -hospitalization -network . Accessed June 20, 2024 14 \n \n  \n  \n \n  Summary \nPublic Health Problem \n• COVID -19-associated hospitalizations and deaths occur all year around, but peak in \nDecember – February \n• COVID -19-associated hospitalizations and deaths are highest in adults aged 75 and older \n• More pediatric hospitalizations and deaths occur each year associated with COVID -19 than \nother select vaccine preventable diseases as the time those recommendations were made \nfor children in the United States \n-Among children hospitalized for COVID -19, 50% had no underlying medical conditions \n-Of those, 18% were admitted to the ICU \n• Racial and ethnic differences in COVID -19 hospitalization rates persist \nICU: Intensive Care Unit 15 \no o o o o o       \n    Public Health Problem \nWork Group Interpretation \nIs COVID -19 disease among persons ≥6 months of age of public health \nimportance? \n No Probably no Probably yes  Yes Varies  Don’t know \nEtR Domain: \nBenefits and Harms \n \n \n \n Summary of available data \n• Benefits and harms of COVID -19 vaccines are based on multiple years of data from \noriginal, bivalent, and 2023 -2024 formula COVID -19 vaccines \n-GRADE \n• Benefits and harms of updated (bivalent or 2023 -2024) COVID -19 vaccines \n-Available data on GRADE outcomes with no studies captured in systematic review \n-Real -world safety and effectiveness monitoring of the 2023 -2024 vaccines \n-Modeling data on potential impact of 2024 -2025 COVID -19 vaccine \nrecommendations \n18 \n       \n    \n    \n GRADE of benefits and harms for 2024 -2025 COVID -19 \nvaccine: PICO questions \nAdults and Adolescents Infants and Children (Pediatric) \nPopulation Persons ages 12 years and older Persons ages 6 months -11 years \nIntervention Updated COVID -19 \nvaccine (bivalent or 2023 -2024) Updated COVID -19 \nvaccine (bivalent or 2023 -2024) \nComparison No updated vaccine* No updated vaccine* \nOutcomes 1. Medically -attended COVID -19 (ED/UC \nvisits) \n2. Hospitalization due to COVID -19 \n3. Death due to COVID -19 \n4. Post -COVID Conditions \n5. Specified serious adverse events 1. Medically -attended COVID -19 (ED/UC \nvisits) \n2. Hospitalization due to COVID -19 \n3. Death due to COVID -19 \n4. MIS-C \n5. Post -COVID conditions \n6. Specified serious adverse events \nPICO: Population, intervention, comparison, outcomes;  ED/UC: emergency department/urgent care; MIS -C: multisystem inflammatory syndrome in children \n*May include people who received any number of doses of prior formulations and unvaccinated \nBolded outcomes are critical; unbolded outcomes are important 19 \nGRADE benefits among adolescents and adults: Forest plot and pooled \nVE estimate against medically -attended COVID -19 (ED/UC visits) (n=5) \n \n      \n             \n               \n    \n      \n \n \n             \na\nNotes: \nED/UC: emergency department/urgent care; VE or vaccine eff.= vaccine effectiveness; CI= confidence intervals ; IV= inverse variance; nr= not reported \nStudies are listed on the y -axis by median days since receipt of an updated dose. Pooled vaccine effectiveness based on a random effects meta -analysis, using adjusted VE estimates on a log \nscale. \nVaccine effectiveness comparisons included an updated dose (either bivalent or 2023 -2024 formulation) compared to no updated dos e (may include people who received any number of doses of \nprior formulations and unvaccinated, definitions varies by included study). \na Author, vaccine formulation, and time since vaccination (median or median range) \n*VE estimate among immunocompetent persons only \nAll studies are case control studies, 1 study is a pre -print, and 3 studies are manufacturer -funded. \nIn sensitivity analyses of pre-prints, manufacturer -funded studies, bivalent vaccine studies, and 2023 -2024 dose studies, the pooled VE point estimates remained stable, and 95% CIs overlapped. 20 \nGRADE benefits among adolescents and adults: Forest plot and \npooled estimate for VE against hospitalization due to COVID -19 \n(n=8) \nNotes: \nVE or vaccine eff.= vaccine effectiveness; CI= confidence intervals ; IV= inverse variance; nr= not reported \nStudies are listed on the y -axis by median days since receipt of an updated dose. Pooled VE based on a random effects meta -analysis, using adjusted vaccine effectiveness estimates on a log scale. a \n      \n                \n                  \n    \n        \n \n     \n   \n   \n                 Vaccine effectiveness comparisons included an updated dose (either bivalent or 2023 -2024 formulation) compared to no updated dos e (may include people who received any number of doses of prior formulations and unvaccinated, \ndefinitions varies by included study). \na Author, vaccine formulation, and time since vaccination (median or median range) \n* Estimate among immunocompetent persons only \n**Maximum follow -up time was 105 days \n*** Maximum follow -up time was 112 days \n6 studies are case control studies, 3 studies are cohort studies, 3 studies are pre -prints, and 3 studies are manufacturer -funde d. \nIn sensitivity analyses that excluded cohort studies, case control studies, pre -prints, manufacturer funded studies, bivalent va ccines, and 2023 -2024 doses, the pooled VE point estimates remained stable, and 95% CIs overlapped. 21 \nGRADE benefits among adolescents and adults: Forest plot and \npooled VE estimate against death due to COVID -19 (n=3) \na \nNotes: \nVE or vaccine eff.= vaccine effectiveness; CI= confidence intervals ; IV= inverse variance; nr= not reported  \n      \n               \n                  \n    \n          \n   \n    \n         \n             Studies are listed on the y -axis by median days since receipt of an updated dose. Pooled VE based on a fixed effects meta -analysis, using adjusted vaccine effectiveness estimates on a log scale \nVaccine effectiveness comparisons included an updated dose (either bivalent or 2023 -2024 formulation) compared to no updated dos e (may include people who received any number of doses of prior formulations and unvaccinated, \ndefinitions varies by included study). \na. Author, vaccine formulation, and time since vaccination (median or median range) \n*Maximum follow -up time was 105 days \n** Maximum follow -up time was 112 days \n1 study is a case control study, 2 studies are cohort studies , 1 study is a pre -print , and 1 study is funded by a manufacturer \nIn sensitivity analyses of pre-prints and manufacturer -funded studies, the pooled VE point estimates remained stable, and 95% CIs overlapped \n22 \n    \n \n     \n  \n  \n  \n  \n    \n  \n \n  \n      \n   \n       \n Interpreting a GRADE certainty assessment \n• A certainty assessment reflects our confidence that the true effect lies close to the estimated \neffect \n• There are 4 certainty levels: \n• High: We are very confident that the true effect lies close to that of the estimated effect. Randomized controlled trial \ncertainty starts here and can be downgraded or upgraded1 . \n• Moderate: We are moderately confident that the true effect lies close to the estimated effect, but there is a possibility \nthat it is substantially different. \n• Low: We have limited confidence that the true effect lies close to the estimated effect; the true effect may be \nsubstantially different from the estimated effect. Observational certainty starts here and can be downgraded or \nupgraded1 . \n• Very low: We have very limited confidence that the true effect lies close to the estimated effect; the true effect is likely \nto be substantially different from the estimated of effect. \n• A certainty assessment does not reflect our confidence in the quality of the individual studies or the \noverall confidence in benefits and harms of the vaccine, which may be informed by additional data \non benefits and harms. \n1. Evidence type may be downgraded due to risk of bias, inconsistency, indirectness, imprecision or other considerations such as publication bias and upgraded for indications of a dose -response \ngradient, large or very large magnitude of effect, and opposing residual confounding. 23 \nSummary of GRADE \nOutcome​ Population  Importance Design Effect Findings​ Final \n(# of studies)  estimate certainty \n(95% CI) assessment \nBenefit  \nAdolescent/adult    Updated COVID -19 vaccine prevents hospitalization due t Low \nHospitalization due \nto COVID -19​Pediatric Critical OBS (8)   VE: 44 (34 -\n53)    COVID -19, although the body of evidence in the pediatric \n   population is limited to indirect data from adolescents \n and adults. Very low \n Death due to \nCOVID -19 Adolescent/adult \nPediatric Important OBS (3)   VE: 23 (8 -36)     Updated COVID -19 vaccine prevents death due to COVID -\n  19, although the body of evidence in the pediatric \n population is limited to indirect data from adolescents \n and adults. Low \nVery low \nPost -COVID \nconditions Adolescent/adult \nPediatric Important OBS (0) -- -\nMIS-C Pediatric Important OBS (0) - - -\nHarms\nCritical -Low \nVery low s\n         \n    ​\no \n \nED/UC: emergency department/urgent care; OBS: observational; VE: vaccine effectiveness; CI: confidence interval; MIS -C: multisys tem inflammatory syndrome in children \nNote:  Vast majority of data captured in systematic review are for mRNA vaccines. 24 Medically -attended \n  COVID -19 (ED/UC \nvisit) Adolescent/adult \nPediatric Critical OBS (5) \nOBS (1)   VE: 43 (30 -\n54) \n  VE: 80 (42 -\n96)      Updated COVID -19 vaccine is effective in preventing \n   medically attended COVID -19 ED/UC visits. Low \nLow \nSpecified serious \nadverse events​Adolescent/adult \nPediatric OBS (2)  In post -authorization safety monitoring, two rare adverse \n   events have been associated with vaccination \n \n  \n   \n  \n    2023 -2024 Formula COVID -19 vaccine effectiveness \n• 2023 -2024 COVID -19 vaccination provided increased protection against symptomatic SARS -CoV-2 infection and COVID -19-associated ED/UC visits and hospitalizations compared to no 2023 -2024 vaccine dose \n• Waning patterns appeared similar to previous COVID -19 vaccine formulations; most durable protection appeared to be for critical illness, though statistical power was lacking in the longest time period since vaccination \n• As with previous COVID -19 vaccine formulations, effectiveness was similar across age groups \n• Receipt of 2023 -2024 COVID -19 vaccine provided protection against JN.1 and other circulating variants, though may be lower than protection provided against XBB sublineage variants \nED: Emergency department | UC: Urgent care \n25 \n  \n  \n    \n \n  \n  COVID -19 mRNA vaccination associated with reduced occurrence \nof Post -COVID Conditions (PCC) following SARS -CoV-2 infection \nAmong children 5 – 17 years: \nCompletion of the original formula \nCOVID -19 vaccine series prior to \ninfection associated with reduced \nlikelihood of symptoms: \n34% for 1 or more PCC symptoms \n47% for respiratory PCC symptoms \n48% for 2 or more PCC symptoms Among adults: \n3 doses of original formula COVID -19 \nvaccine prior to infection associated with \nreduced likelihood of symptoms: \n24% for 2 or more PCC symptoms \n27% for cardiovascular/respiratory \nsymptoms \n42% for gastrointestinal symptoms \n26% for neurological symptoms \n33% for other non -specific symptoms \nUnpublished data from the HEROES/RECOVER, PROTECT cohorts. \nHEROES Protocol ; RECOVER Protocol ; PROTECT Protocol 26 \n  \n \n  \n \n \n      COVID -19 vaccine effectiveness against Multisystem \nInflammatory Syndrome in Children (MIS -C) in US \nchildren ages 5 -18 years old \n• Multicenter case -control public health investigation from July 1, 2021 –April 7, 2022 \n• Compared odds of receiving 2 doses of BNT162b2 vaccine ≥28 days before admission between MIS -C \ncase -patients and hospital -based controls who tested negative for SARS -CoV-2 \n-304 MIS-C case patients ( 92% unvaccinated) \n-502 controls (69% unvaccinated) \n• A lower proportion of vaccinated patents required life \nsupport or died during period of Delta \nvariant predominance \n• One unvaccinated MIS -C case -patient (12 –18 years) \nrequired ECMO, and 1 unvaccinated patient (5 –11 \nyears) died \nZambrano LD, et al. Clin Infect Dis. 2022 Aug 4:ciac637 ECMO = extracorporeal membrane oxygenation \n 27 \n \n  \n COVID -19 vaccine safety \n• COVID -19 vaccines have a favorable safety profile as demonstrated by \nrobust safety surveillance over 3 years of COVID -19 vaccine use \n-Anaphylactic reactions have been rarely reported following receipt of COVID -19 \nvaccines \n-Rare risk of myocarditis and pericarditis predominately in males ages 12 -39 years \n• No myocarditis or pericarditis signal in the Vaccine Safety Datalink for the \n2023 -2024 Formula COVID -19 vaccine, however, this may be limited by low \nuptake \n-Reactogenicity symptoms are overall less frequent and severe among older adults \ncompared with adolescents and younger adults \n28 \n \n \n \n  \n \n  \n \n \n Longer term impact of vaccine associated myocarditis \n•Vaccine -associated myocarditis is a rare risk of COVID -19 vaccination.\n•Acute clinical picture tends to resolve quickly1\n-Majority of patients had recovered at 90 days with symptoms improving over time\n•Small subset with persistent MRI findings (e.g., late gadolinium\nenhancement), with unclear correlation to symptoms2\n-Additional follow up is needed to determine the long -term impact of these MRI\nfindings\n1.https://www.sciencedirect.com/science/article/pii/S2352464222002449?via%3Dihub\n2.https://papers.ssrn.com/sol3/papers.cfm?abstract_id=4681858#:~:text=Interpretation%3A%20COVID%2D19%20vaccine%2D,continued%20s urveillance%20in%20C%2DVAM\nMRI: magnetic resonance imaging 29 \n \n  \n        \n  \n       \n         \n \n   \n \n    \n    \n   \n  Summary of the Vaccine Safety Datalink (VSD) Rapid \nCycle Analysis for the 2023 -2024 COVID -19 vaccine \n• The VSD identified two statistical signals for mRNA COVID -19 vaccines during the 2023 -2024 season \n-Guillain -Barré syndrome (GBS) following Pfizer COVID -19 vaccine among people aged ≥65 years \n• An association between mRNA COVID -19 vaccines and GBS had not been observed prior to this season in \nVSD or other systems \n• The increased rate ratio observed during the 2023 -2024 season may or may not represent a true risk \n• If there is a true risk, it is estimated to be similar to what is considered acceptable for other adult vaccines \n-Ischemic stroke following Moderna (aged ≥65 years) and Pfizer (aged 50 -64 years) COVID -19 vaccines \n• The VSD previously observed a statistical signal for ischemic stroke during 2022 -2023 for bivalent Pfizer \nCOVID -19 vaccine (aged ≥65 years) \n• Available data do not provide clear and consistent evidence of a safety problem for ischemic stroke with \nmRNA COVID 19 vaccines \n• No other new or unexpected safety concerns were identified for the 2023 -2024 COVID -19 vaccines \n• Any real or theoretical risks of vaccine adverse events need to be placed in the context of the benefits \nof COVID -19 vaccines in preventing COVID -19 and its potentially serious complications 30 \n   \n   \n \n \n  \n  \n  \n          \n      \n             \n          \n Models of potential impact of different 2024 -2025 \nCOVID -19 vaccine recommendations \n• Assumptions of COVID -19 Scenario Modeling Hub Round 18 \n• Six scenarios focusing on three vaccine recommendation scenarios under high and \nlow rates1 of immune escape \n-No vaccine recommendation2 vs recommendation only for persons at high -risk vs \nuniversal recommendation \n-High -risk defined as those ages ≥ 65 years and those with underlying conditions3 \n• Vaccine uptake assumptions based on 2023 -2024 COVID -19 vaccine coverage4 \n• Assumes vaccine available on September 1st with 75% VE against hospitalization \n-Constant rate of immune escape and waning applied starting September 1st \n• Models projected 1 year into the future \n1. Low immune escape occurs at a constant rate of 20% per year and high immune escape occurs at a constant rate of 50% per year \n2. The no vaccine recommendation scenario allowed for naïve children aging into eligibility to be vaccinated \n3. Ko JY, Danielson ML, Town M, et al. Risk Factors for Coronavirus Disease 2019 (COVID -19)–Associated Hospitalization: COVID -19–Associated Hospitalization Surveillance Network and Behavioral Risk Factor Surveillance \nSystem. Clinical Infectious Diseases. 2021;72(11):e695 -e703. doi:10.1093/ cid/ciaa1419 \n4. https://www.cdc.gov/vaccines/imz -managers/coverage/covidvaxview/index.html . Assumption of approximately 21% of adults, 39% of those ≥65 years, 32% of those with underlying conditions \nVE: vaccine effectiveness 31 \nUniversal vaccine recommendations projected to prevent about \n30,000 more hospitalizations over the next year compared with \na risk -based recommendation \nRecommendation \nType1Percent prevented (95% CI) Total prevented (95% CI) \nUniversal v. None \nHigh -Risk v. None \nUniversal v. High -Risk   \n \n          \n \n1.None = no vaccine recommendation; High -risk = recommended for those ages ≥ 65 years and those with underlying conditions; Uni versal = universal vaccine recommendation 32 \nDomain Equity Question: \nAre the desirable and undesirable anticipated effects demonstrated across \nall populations equally? \n \n \n \n  \n \n Are the desirable and undesirable anticipated effects \ndemonstrated across all populations equally? \n• There is no evidence to suggest that COVID -19 vaccine effectiveness \nvaries substantially by race/ethnicity1,2 \n-Differences in vaccine hesitancy/uptake, crowding, access to care, and prior \ninfection could impact vaccine effectiveness and these factors may also differ by \nrace/ethnicity \n• There is no evidence to suggest that COVID -19 vaccine safety profiles vary by \nrace/ethnicity, however risk has been shown to differ by age and sex \n-Risk for myocarditis is highest in adolescent and young adult males \n• Benefits and harms for the U.S. population are best assessed when clinical trial and \nstudy populations are optimally representative of the U.S. population \n1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9619452/ \n2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9763212/ 34 \n \n  \n \n  \n Summary \nBenefits and Harms \n• 2023 -2024 COVID -19 vaccine is effective in preventing ED/UC visits and preventing \nsevere outcomes related to COVID -19 (e.g., hospitalization, death); waning of \nimmunity is expected \n• COVID -19 vaccines continue to have a favorable safety profile as \ndemonstrated by robust safety surveillance over 3 years of COVID -19 vaccine use \n-Ischemic stroke and GBS signals in the VSD are not clear or consistent, and \nare seen in the age groups (adults ≥ 50 years and adults ≥ 65 years, \nrespectively) with the highest burden of disease that would benefit the most from \nupdated COVID -19 vaccination \n• Modeling projects more hospitalization averted when 2024 -2025 COVID -19 vaccines \nare universally recommended compared to no recommendation or recommended \nonly for those at high risk \nVSD: Vaccine Safety Datalink | GBS: Guillain -Barre Syndrome 35 \n \n \n Benefits and Harms \nHow substantial are the desirable anticipated effects? \n• How substantial are the anticipated effects for each main outcome for \nwhich there is a desirable effect? \no o o o o o    Minimal  Small Moderate  Large Varies  Don’t know \no o o o o o   \n \n  Benefits and Harms \nHow substantial are the undesirable anticipated effects? \n• How substantial are the anticipated effects for each main outcome for \nwhich there is an undesirable effect? \n Minimal  Small  Moderate  Large Varies  Don’t know \n Benefits and Harms \nDo the desirable effects outweigh the undesirable effects? \n• What is the balance between the desirable effects relative to the \nundesirable effects? \noFavors intervention (2024 – 2025 Formula COVID -19 vaccine) \noFavors comparison (no vaccine) \noFavors both \noFavors neither \noUnclear \n EtR Domain: \nValues \n     \n    \n   1 in 5 Americans now say COVID -19 is a major threat \nto public health \n% of U.S. adults who say COVID -19 is a major threat to the health \nof the U.S. population \n80 \n47 66 64 67 65 63 61 \n57 \n41 \n20 \n20 30 40 50 60 70 \n10 \n0 \nMar '20 Mar '20 Apr '20 Jul '20 Nov '20 Feb '21 Aug '21 Jan '22 May '22 Feb '24 \nPew Research Center. March 7, 2024. How Americans View the Coronavirus, COVID -19 Vaccines Amid Declining Levels of Concern. https://www.pewresearch.org/science/2024/03/07/how -americans -view -the-\ncoronavirus -covid -19-vaccines -amid -declining -levels -of-concern/ Accessed April 23, 2024 40 \n   \n    \n     \n  \n \n    \n  Concern about risk of COVID -19 by age, February 2024 \n% of U.S. adults who say they are very/somewhat concerned that they… \nSurvey conducted among 10,133 U.S. adults from February 7 -11, 2024. \nPew Research Center. March 7, 2024. How Americans View the Coronavirus, COVID -19 Vaccines Amid Declining Levels of Concern. https://www.pewresearch.org/science/2024/03/07/how -americans -view -the-\ncoronavirus -covid -19-vaccines -amid -declining -levels -of-concern/ Accessed April 23, 2024 12 14 10 16 \n29 26 28 28 \n0 10 20 30 40 50 65+ 50-6430-2918-29Age, years Might unknowingly spread \nCOVID -19 to others \nvery concerned Somewhat concerned 11 11 8 10 \n21 18 14 16 \n0 5 10 15 20 25 30 35 65+ 50-6430-4918-29Age, years Will get COVID -19 and \nrequire hospitalization \nVery concerned Somewhat concerned \n41 \n    \n   \n     \n         \n   \n  Key attitudes and experiences among parents of children 6 months -17 years, December 2023 \nNational Immunization Survey -Child COVID -19 Module (NIS -CCM) \nCOVID -19 Vaccination Key Attitudes and Experiences by Age Group Among Parents of Children Ages \n6 Months -17 Years, NIS -CCM, December 2023 \n80 \n30 35 51 \n28 39 56 \n30 57 69 \n0 10 20 30 40 50 60 70 Percent \nModerately or very concerned about child getting COVID-19 Confidence that COVID-19 vaccine is very or completely safe for Confidence that COVID-19 vaccine is somewhat or very \ndisease child important to protect child \n6 months - 4 years 5 - 11 years 12 - 17 years \nThe December estimates are based on data collected November 26 through December 30, 2023. \nCDC. COVID -19 Vaccination Coverage and Vaccine Confidence Among Children. https://www.cdc.gov/vaccines/imz -managers/coverage/covidvaxview/interactive/children.html Accessed April 30, 2024 42 \n \n \n   \n             \n  Key attitudes and experiences among adults 18 years and older, April 2024 \nNational Immunization Survey -Adult COVID Module (NIS -ACM) \nCOVID -19 Vaccination Key Attitudes and Experiences by Age Group Among Adults Ages ≥18 \nYears, NIS -ACM, April 2024 \n80 \n21 51 64 \n30 55 65 \n35 63 74 \n0 10 20 30 40 50 60 70 Percent \nVery or moderately concerned about COVID-19 disease Confidence COVID-19 vaccine is very or completely safe Confidence that COVID-19 vaccine is somewhat or very \nimportant to protect me \n18 - 49 years 50 - 64 years 65+ years \nThe April estimates are based on data collected April 1 through April 27, 2024. \nCDC.COVID -19 Vaccination Coverage and Vaccine Confidence Among Adults. https://www.cdc.gov/vaccines/imz -managers/coverage/covidvaxview/interactive/adults.html Accessed May 30, 2024 43 \n \n EtR Domain: \nIs there important variability in how patients or populations value the \noutcome? \n  \n \n     \n        \n   Key attitudes and experiences among parents of children 6 months -17 years, \nDecember 2023 \nNational Immunization Survey -Child COVID -19 Module (NIS -CCM) \nCOVID -19 Vaccination Key Attitudes and Experiences by Race & Ethnicity Among Parents of \nChildren Ages 6 Months -17 Years, NIS -CCM, December 2023 \n80 \n33 47 68 \n23 45 51 \n43 \n40 70 \n30 44 67 \n0 10 20 30 40 50 60 70 Percent Hispanic \nWhite, non-Hispanic \nBlack, non-Hispanic \nOther or multiple races, non-Hispanic \nModerately or very concerned about child getting \nCOVID-19  disease Confidence COVID-19 vaccine is very or completely \nsafe for  child Confidence that COVID-19 vaccine is somewhat or \nvery important to protect child \nThe December estimates are based on data collected November 26 through December 30, 2023. \nCDC. COVID -19 Vaccination Coverage and Vaccine Confidence Among Children. https://www.cdc.gov/vaccines/imz -managers/coverage/covidvaxview/interactive/children.html Accessed April 30, 2024 45 \n  \n   \n    \n           \n  Key attitudes and experiences among adults 18 years and older, April 2024 \nNational Immunization Survey -Adult COVID Module (NIS -ACM) \nCOVID -19 Vaccination Key Attitudes and Experiences by Race & Ethnicity Among Adults Age ≥18 Years, NIS -ACM, April 2024 \nAI/AN: American Indian or Alaska Native; NH/PI: Native Hawaiian or Other Pacific Islander \nThe April estimates are based on data collected April 1 through April 27, 2024. \nCDC.COVID -19 Vaccination Coverage and Vaccine Confidence Among Adults. https://www.cdc.gov/vaccines/imz -managers/coverage/covidvaxview/interactive/adults.html Accessed May 30, 202422 49 73 \n26 56 63 \n35 50 74 \n29 64 85 \n20 48 78 \n31 39 52 \n28 55 65 \n0 10 20 30 40 50 60 70 80 90 100 \nVery or moderately concerned about COVID-19 \ndisease Confidence that COVID-19 vaccine is very or \ncompletely safe Confidence that COVID-19 vaccine is somewhat \nor very important to protect me Percent Hispanic \nWhite, non-Hispanic \nBlack, non-Hispanic \nAsian, non-Hispanic \nNH/PI, non-Hispanic \nAI/AN, non-Hispanic \nOther or multiple races, non-Hispanic \n46 \n   \n    \n      \n  \n \n   \n  Concern about risk of COVID -19 by race and ethnicity, \nFebruary 2024 \n% of U.S. adults who say they are very/somewhat concerned that they… \nWhite 5 \nBlack \nHispanic \nAsian \n0 Will get COVID -19 and \nrequire hospitalization \n15 \n20 \n16 22 \n18 18 \n10 20 30 \nVery concerned Somewhat concerned 23 \n40 50 White 8 \nBlack \nHispanic \nAsian \n0 Might unknowingly spread \nCOVID -19 to others \n27 \n24 27 \n18 31 \n20 34 \n10 20 30 40 50 \nVery concerned Somewhat concerned 60 \nSurvey conducted among 10,133 U.S. adults from February 7 -11, 2024. \nPew Research Center. March 7, 2024. How Americans View the Coronavirus, COVID -19 Vaccines Amid Declining Levels of Concern. https://www.pewresearch.org/science/2024/03/07/how -americans -view -the-\ncoronavirus -covid -19-vaccines -amid -declining -levels -of-concern/ Accessed April 23, 2024 47 \n   \n    \n      \n  \n \n   \n  Concern about risk of COVID -19 by income, \nFebruary 2024 \n% of U.S. adults who say they are very/somewhat concerned that they… \nSurvey conducted among 10,133 U.S. adults from February 7 -11, 2024. \nPew Research Center. March 7, 2024. How Americans View the Coronavirus, COVID -19 Vaccines Amid Declining Levels of Concern. https://www.pewresearch.org/science/2024/03/07/how -americans -view -the-\ncoronavirus -covid -19-vaccines -amid -declining -levels -of-concern/ Accessed April 23, 2024 19 10 9 \n27 27 29 \n0 10 20 30 40 50 Lower income Middle income Upper income Might unknowingly spread \nCOVID -19 to others \nVery concerned Somewhat concerned 17 7 5 \n21 16 11 \n0 5 10 15 20 25 30 35 40 Lower income Middle income Upper income Will get COVID -19 and \nrequire hospitalization \nVery concerned Somewhat concerned \n48 \n \n  \n \n   \n  Summary \nValues \n• Approximately 30% of parents of children ages 6 months – 17 years reported \nconcern about their child getting COVID -19, but confidence in COVID -19 vaccine \nsafety and vaccine importance was highest among parents of adolescents \n• Adults ages 65 years and older were more concerned about COVID -19 disease and \nhad higher confidence in vaccine safety and vaccine importance than those <65 \nyears \n• Racial and ethnic minority groups, older adults, and those with lower incomes are \nmore concerned about getting COVID -19 than other groups \n49 \no o o o o o  Minimal  Small  Moderate Large  Varies  Don’t know  \n \n  \n  Values \nCriteria 1: \nDo persons ≥6 months of age feel that the desirable effects are large relative \nto undesirable effects? \n• How do persons ≥6 months of age view the balance of desirable versus \nundesirable effects? \n• Would persons ≥6 months of age feel that the benefits outweigh the \nharms? \n  \no\no\noo\no \n \n  \n Values \nCriteria 2: \nIs there important uncertainty about, or variability in, how persons ≥6 \nmonths of age value the main outcomes? \n• Is there evidence that the variability is large enough to lead to different \ndecisions? \nMajority opinion\nMinority opinion Important uncertainty or variability \nProbably important uncertainty or variability \nProbably not important uncertainty or variability \nNo important uncertainty or variability \nNo known undesirable outcomes \n  EtR Domain: \nAcceptability \nDeclining share of Americans have the most up -to-\ndate level of protection against COVID -19 \n% of U.S. adults who report that they are up to date with COVID -19 vaccines \n80 Nov. 2021 \nAll U.S. adults eligible for COVID -19 First booster dose Sept. 2022 vaccination 69 authorized for all eligible Bivalent vaccine is authorized 70 U.S. adults \nSept. 2023 \nUpdated (2023 -2024) vaccines 60 \nare approved/authorized \n48\n    \n    \n         \n  \n \n  \n \n \n \n50 \n40 34 \n2830 \n20 \n10 \n0 \nApr '21 Aug '21 Jan '22 Mar '23 Feb '24 \nSurvey conducted among 10,133 U.S. adults from February 7 -11, 2024. \nPew Research Center. How Americans View the Coronavirus, COVID -19 Vaccines Amid Declining Levels of Concern. https://www.pewresearch.org/science/2024/03/07/how -\namericans -view -the-coronavirus -covid -19-vaccines -amid -declining -levels -of-concern/ Accessed April 23, 2024 53 \n   \n \n      \n          \n       \n Percent of adults and children who received 2023 -24 COVID -19 vaccine \nNational Immunization Survey -Adult COVID Module (NIS -ACM) and -Child COVID Module (NIS -CCM) \nSeptember 2023 -April 2024 \nCOVID -19 Vaccination Coverage with 2023 -24 Vaccine COVID -19 Vaccination Coverage with 2023 -24 Vaccine \nAmong Adults ≥18 Years, NIS-ACM Among Children 6 Months -17 Years, NIS -CCM Vaccinated with 2023 -24 COVID -19 vaccine (%) 50 \n40 \n30 \n20 \n10 \n0 \n9/30/23 10/31/23 11/30/23 12/31/23 1/31/24 2/29/24 3/31/24 4/30/24 \nWeek end date All adults 18+ \n75+ \n65-74\n50-64\n40-49\n30-39\n18-2950 \n40 \n30 \n20 \n10 \n0 \n9/30/23 10/31/23 11/30/23 12/31/23 1/31/24 2/29/24 3/31/24 4/30/24 \nWeek end date Vaccinated with 2023 -24 COVID -19 vaccine (%) \nAll children 6m-17y \n12-17y\n5-11y\n6m-4y \nhttps://www.cdc.gov/vaccines/imz -managers/coverage/covidvaxview/index.html 54 \nIntent to get 2024 -25 COVID -19 vaccine among adults ≥18 years of age, by \ndemographics,* Omnibus Surveys, May 2 -26, 2024 (N=4,276) \nDefinitely will get Definitely will not Probably will Probably will not Unsure \nOverall (N=4,276) \nMale (N=2,080) \nFemale (N=2,196) \nAge 18-49 (N=2,146) \nAge 50-64 (N=1,088) \nAge 65+ (N=1,042) \nhite, non-Hispanic (N=2,837) \nBlack, non-Hispanic (N=494) \nHispanic (N=621) \nOther, non-Hispanic (N=324) 23.6 14.3    \n      \n 23.3 13.2 \n20.6 20.9 26.0 23.9 15.4 \n39.2 16.9 12.3 15.5 \n10.8 36.3 \n35.6 \n20.9 \n13.5 13.9 36.1 \n19.6 12.4 23.2 \n18.6 11.9 31.7 \n17.1 18.0 23.4 13.7 32.6 \n31.9 \n33.3 14.4 \n13.1 Inco\nInsured (N=3,645) \nUninsured (N=301) 25.3 22.7 21.2 20.4 13.1 \n16.1 20.1 \n15.7 \n14.5 16.6 15.7 \n13.7   \n  \n \n  \n 10.9 \n15.7 \n11.9 \n14.4 $50,000- $74,999 (N=805) Suburban (N=2,008) \nRural (N=750) \nme $24,999 or less (N=512) \n$25,000- $49,999 (N=775) Urban (N=1,518) \n$75,000+ (N=2,184) \nNortheast (N=669) \nMidwest (N=1,070) \nSouth (N=1,474) \nWest (N=1,063) 13.5 \n14.0 \n15.1 16.7 \n14.7 \n13.7 27.6 \n32.1 \n43.7 \n14.7 \n15.0 \n12.7 \n13.8 26.3 21.8 23.3 23.2 14.6 \n14.6 15.4 \n12.8 \n18.4 17.1 14.8 \n13.2 26.3 16.0 \n24.2 15.0 \n15.6 11.8 \n35.6 \n31.4 \n33.0 \n32.1 \n32.1 \n32.3 \n35.6 \n28.3 \n24.8 \n12.8 14.4 \n12.1 15.8 \n15.1 13.0 \n19.5 31.9 \n40.6 \n0 25 50 75 100 \nWeighted % 18.3 22.3 24.6 23.4 14.8 15.4 \n14.6 \n15.0 14.5 \n16.3 \n12.7 \n12.1 \n18.8 16.3 13.6 \n0 25 50 75 100 \nWeighted % W \n \n                \n      \n         \n          *NORC and Ipsos base urbanicity on different, but comparable measures. NORC uses Census tract -based RUCA (Rural -Urban -Commuting Area) codes, whereas Ipsos uses Office of Management and Budget's CBSA (Core Based Statistical Area) classification. †Insured group includes \nplans purchased through employer, insurance companies, marketplaces, military insurance, Medicare, Medicaid, VA, IHS, and \"ot her\". \nOmnibus Surveys: Data for this analysis were collected through the Ipsos KnowledgePanel and NORC AmeriSpeak Omnibus Surveys, which use probability -based panels to survey a nationally representative sample of U.S. adults aged 18 \nyears and older. CDC fields questions about vaccination status, intent, knowledge, attitudes, beliefs, and behaviors on each survey for 2 waves each month, for a combined sample size of ~4,000 respondents. 55 \nIntent to get an annual COVID -19 vaccine among adults ≥18 years of age, by \ndemographics,* Omnibus Surveys, May 2 -26, 2024 (N=4,270) \nOverall (N=4,270) \nMale (N=2,079) \nFemale (N=2,191) \nAge 18-49 (N=2,142) \nAge 50-64 (N=1,087) \nAge 65+ (N=1,041) \nite, non-Hispanic (N=2,834) \nlack, non-Hispanic (N=492) \nHispanic (N=620) \nther, non-Hispanic (N=324) 35.5 \n35.9 \n30.1 \n34.7 \nUrban (N=1,519) \nSuburban (N=2,003) \nRural (N=748) 37.0  \n    \n      \n  \n 36.1 \n25.2 \n0 Every year Some yea Never \n34.5 23.9 \n34.6 \n34.4 23.4 \n24.4 \n24.7 \n35.9 \n55.6 28.8 \n21.1 41.6 I   \n \n  \n ncome $24,999 or less (N=508) \n$25,000- $49,999 (N=776) \n$50,000- $74,999 (N=805) \n$75,000+ (N=2,181) \nNortheast (N=669) \nMidwest (N=1,068) \nSouth (N=1,469) \nWest (N=1,064) 27.9 \n33.9 \n34.0 \n36.7 45.8 \n41.9 \n42.2 \n40.2 26.3 \n24.2 \n23.9 \n23.1 \n36.0 \n33.1 \n32.0 \n38.6 40.7 \n42.7 \n44.5 \n36.7 23.3 \n24.2 \n23.5 \n24.7 \n36.1 \n18.5 40.2 \n59.8 23.7 \n21.7 Insured (N=3,635) \nUninsured (N=302) \n0 25 50 75 100 \nWeighted % 42.0 \n41.3 \n46.5 \n43.0 \n28.9 15.5 \n45.0 19.5 \n33.5 \n41.0 28.9 \n30.8 30.6 \n34.5 \n26.4 \n22.8 36.6 \n41.0 \n21.8 53.0 \n25 50 75 100 \nWeighted % Wh\nB\nO \n                \n      \n         \n          rs \n*NORC and Ipsos base urbanicity on different, but comparable measures. NORC uses Census tract -based RUCA (Rural -Urban -Commuting Area) codes, whereas Ipsos uses Office of Management and Budget's CBSA (Core Based Statistical Area) classification. †Insured group includes \nplans purchased through employer, insurance companies, marketplaces, military insurance, Medicare, Medicaid, VA, IHS, and \"ot her\". \nOmnibus Surveys: Data for this analysis were collected through the Ipsos KnowledgePanel and NORC AmeriSpeak Omnibus Surveys, which use probability -based panels to survey a nationally representative sample of U.S. adults aged 18 \nyears and older. CDC fields questions about vaccination status, intent, knowledge, attitudes, beliefs, and behaviors on each survey for 2 waves each month, for a combined sample size of ~4,000 respondents. 56 \n    \n             \n  \n \n   \n  Key attitudes and experiences among parents of children 6 months -17 years, \nDecember 2023 -National Immunization Survey -Child COVID Module (NIS -CCM) \nReason for Not Getting the COVID -19 Vaccine Among Respondents with \nUnvaccinated Children Ages 6 Months -17 Years, NIS -CCM, December 2023 \nConcerned about side effects \nCOVID-19 vaccine is ineffective \nChild unlikely to get very sick from COVID-19 \nChild unlikely to get COVID-19 \nDon't like needles or shots \nHard to get to vaccination site/sites not open at convenient times \nCOVID-19 vaccine costs too much 2 2 17 21 56 58 88 \n0 10 20 30 40 50 60 70 80 90 100 \nPercent \nThe December estimates are based on data collected November 26 through December 30. \nCDC. COVID -19 Vaccination Coverage and Vaccine Confidence Among Children. https://www.cdc.gov/vaccines/imz -managers/coverage/covidvaxview/interactive/children.html Accessed April 30, 202457 \n     \n           \n  \n   \n  \n    \n \n Key attitudes and experiences among parents of children ages 6 months through 17 \nyears, December 2023 -National Immunization Survey -Child COVID Module (NIS -CCM) \nCOVID -19 Vaccination Key Attitudes and Experiences by Age Group Among \nParents of Children Ages 6 Months –17 Years, NIS -ACM, December 2023 \n28 27 28 \n0 10 20 30 40 50 60 70 80 90 100 \nHealthcare provider recommended I get a 2023-2024 COVID-19 vaccine Percent6 months –4 years \n5–11 years \n12–17 years \nThe December estimates are based on data collected November 26 through December 30 2023. \nCDC. COVID -19 Vaccination Coverage and Vaccine Confidence Among Children. https://www.cdc.gov/vaccines/imz -managers/coverage/covidvaxview/interactive/children.html Accessed May 30, 2024 58 \n  \n \n   \n \n   \n Key attitudes and experiences among adults 18 years and older, April 2024 \nNational Immunization Survey-Adult COVID Module (NIS-ACM) \nCOVID-19 Vaccination Key Attitudes and Experiences by Age Group \nAmong Adults Age ≥18 Years, NIS -ACM, April 2024 \n100 \n90 \n80 \n70 \n60 \n18 - 49 years \n50 50 - 64 years \n65+ years 40 \nHealthcare provider recommended I get a 2023-2024 COVID-19 vaccine Percent \n17 24 27 \n0 10 20 30 \n   \n        The April estimates are based on data collected April 1 through April 27. \nCDC.COVID -19 Vaccination Coverage and Vaccine Confidence Among Adults. https://www.cdc.gov/vaccines/imz -managers/coverage/covidvaxview/interactive/adults.html Accessed May 30, 2024 59 \n    \n  \n  \n  \n \n    \n  \n   \n \n  \n         \n      \n Top COVID -19 vaccination concerns and issues among \nadults ≥18 years Omnibus Surveys, January 5 -29, 2024 \n• Among those that reported they received the 2023 -2024 COVID -19 vaccine or definitely would: \n-The majority had no concerns or issues with COVID -19 vaccination \n• 67% in aged 18 -59 years; 83% in aged ≥60 years \n• Among those that reported that they probably would receive the 2023 -2024 COVID -19 vaccine or were unsure: \n-Unknown serious side effects and too busy or kept forgetting were the most commonly reported issues for \nthose 18 -59 years old \n-Effectiveness and unknown serious side effects were the most commonly reported issues for those ≥60 years \n• Among those that reported that they probably/definitely would not get the 2023 -2024 vaccine: \n-Unknown serious side effects, not enough studies, and distrust of government/pharma were the most \nfrequently reported concerns \nSource: CDC, unpublished data \nOmnibus Surveys: Data for this analysis were collected through the Ipsos KnowledgePanel and NORC AmeriSpeak Omnibus Surveys, which use probability -based panels to survey a nationally representative \nsample of U.S. adults aged 18 years and older. CDC fields questions about vaccination status, intent, knowledge, attitudes, b eliefs, and behaviors on each survey for 2 waves each month, for a combined \nsample size of ~4,000 respondents. 60 \n Domain Equity Question: \nIs the intervention equally acceptable across all populations? \n  \n \n \n  \n  \n       Is the intervention equally acceptable across all \npopulations for children? \nAmong children ages 6 months – 17 years responding to the NIS -CCM during April 1 – \n27, 2024: \n• Vaccination coverage differed by race/ethnicity \n-Coverage was highest among White, non -Hispanic children and lowest among \nBlack, non -Hispanic children \n• Vaccination coverage was higher in urban/suburban areas compared with rural areas \n• Children covered by private health insurance had higher vaccination coverage than \nchildren who were uninsured or covered by Medicaid \n• Vaccination coverage increased with increasing household income \nCDC. COVID -19 Vaccination Coverage and Vaccine Confidence Among Children. https://www.cdc.gov/vaccines/imz -managers/coverage/covidvaxview/interactive/children.html Accessed May 24, 2024 62 \n \n \n \n \n \n         \n Is the intervention equally acceptable across all \npopulations for adults? \nAmong adults ages ≥18 years responding to the NIS -ACM during April 1 – 27, 2024: \n• Vaccination coverage differed by race/ethnicity \n-Coverage was highest among White, non -Hispanic adults and lowest among \nAmerican Indian/Alaska Native and Native Hawaiian/Other Pacific Islander adults \n• Vaccination coverage was higher in urban/suburban areas compared with rural areas \n• Adults with health insurance had significantly higher vaccination coverage than \nadults without insurance \n• Vaccination coverage increased with increasing household income \nCDC. COVID -19 Vaccination Coverage and Vaccine Confidence Among Adults. https://www.cdc.gov/vaccines/imz -managers/coverage/covidvaxview/interactive/adults.html Accessed May 24, 2024 63 \n  \n \n \n \n Summary \nAcceptability \n• Vaccine coverage with at least 1 dose of 2023 -2024 COVID -19 vaccine was \napproximately 20% in adults aged ≥ 18 years \n-From August 2021 to February 2024, the percentage of adults who report being \nup to date with COVID -19 vaccination has decreased from 69% to 28% \n• Concern about side effects is the most likely reason for not being vaccinated \n• Less than 30% of people report having received a healthcare provider \nrecommendation for the 2023 -2024 COVID -19 vaccine \n• COVID -19 vaccine coverage varies by age, race and ethnicity, metropolitan statistical \narea, insurance status and household income \n64 \no o o o o o       \n \n \n  Acceptability \nWould recommending a dose of the 2024 – 2025 Formula COVID -19 vaccine \nfor persons ≥6 months of age be acceptable to key stakeholders? \n• Are there key stakeholders that would not accept the distribution of \nbenefits and harms? \n• Are there key stakeholders that would not accept the undesirable effects \nin the short term for the desirable effects (benefits) in the future? \n No  Probably no  Probably yes Yes  Varies  Don’t know \nMajority opinion Minority opinion \nEtR Domain: \nFeasibility \n  \n   \n   \n \n \n  \n  \n \n   \n Feasibility of vaccine implementation \n• No substantial clinical consideration changes expected \n– Supporting tools and documents from 2023 -2024 vaccine will not need to be significantly \nrevised or reprogrammed, but COVID -19 vaccine recommendations remain complex \n• There will continue to be single dose presentations and minimum order quantities \n– Moderna \n• ≥6 months: manufacturer -prefilled syringes (10 -pack) \n– Novavax \n• ≥ 12 years: manufacturer -prefilled syringes (10 -pack) \n– Pfizer -BioNTech \n• ≥ 12 years: manufacturer -prefilled syringes (10 -pack) \n• 5 – 11 years: single dose vial (10 -pack) \n• 6 months – 4 years: 3 -dose multi -dose vial (10 -pack) \n• Preparation has not changed \n– Moderna and Novavax vaccines require no dilution \n– Pfizer -BioNTech vaccine requires dilution for 6 month – 4 year formulation \nCDC, Immunization Services Division, internal planning documents 67 \n \n \n  \n \n \n \n   Storage and handling \n• Moderna: Frozen until expiration; 30 days at refrigerator storage \n• Novavax: Refrigerator storage (stable at 2 -8°C ) \n• Pfizer -BioNTech \n– Prefilled syringes (≥12 years): Refrigerator storage (2 -8°C), never frozen \n– Vials (6 months – 11 years): Ultra -cold storage until expiration; 10 weeks at \nrefrigerator storage; use within 12 hours of dilution \n• Ultra -cold storage continues to be a challenge; most provider offices do not \nhave a unit \nCDC, Immunization Services Division, internal planning documents 68 \n \n   \n \n        \n \n Barriers to implementation \n• Increasingly complex routine vaccination schedule, which includes immunization \nproducts for three viral respiratory diseases1 \n– Need more storage space to store all recommended immunization products \n– Increased need for education across vaccination provider types \n– More opportunities for vaccine administration errors \n• Financial burden for healthcare practices with costly vaccine and low demand and \nfor uninsured and underinsured with the end of the Bridge Access Program2 \n• Fewer primary care practices carry COVID -19 vaccine potentially introducing barriers \nto access, particularly for those with difficulty traveling to another location \nfor vaccination \n1. COVID -19 vaccine, Influenza vaccine, RSV vaccine, and Nirsevimab , a long -acting monoclonal antibody for RSV prevention in infants \n2. https://www.cdc.gov/vaccines/programs/bridge/index.html \nCDC, Immunization Services Division, internal planning documents 69 \n Domain Equity Question: \nIs the intervention equally feasible to implement across all populations? \n \n  \n  \n \n \n \n \n \n  COVID -19 vaccine access \n• \n-\n• \n-Free updated COVID -19 vaccines are available to most people living in the U.S. \nthrough their private health insurance, Medicare, and Medicaid plans \nEligible children are able to receive COVID -19 vaccines through the existing \nVaccines for Children (VFC) program \nHowever, there are 25 -30 million adults without health insurance and additional \nadults whose insurance does not cover all COVID -19 vaccination costs \nBridge Access Program1, which provides free updated COVID -19 vaccines to adults \nwithout health insurance and adults whose health insurance does not cover all \nCOVID -19 vaccine costs , will end in August 2024, which will result in inequities in \nvaccine access \n1. https://www.cdc.gov/vaccines/programs/bridge/index.html 71 \n  \n \n \n  \n \n \n    \n \n  Summary \nFeasibility \n• The 2024 – 2025 COVID -19 vaccine will continue to consist of single dose vial \npresentations and smaller minimum order quantities \n-Storage and handling requirements will remain the same as well \n• The increasingly complex routine vaccination schedule, which includes \nimmunizations for three seasonal viral respiratory diseases, presents potential \nbarriers to implementation such as limited storage space due to more vaccines, \nmore opportunities for vaccine administration errors and the need for increased \neducation among vaccine providers \n• Vaccines will continue to be accessible; however, the end of the temporary Bridge \nAccess Program will result in decreased vaccine access for underserved populations \n72 \n     \n \n    \n \n  \n    Feasibility \nIs the 2024 – 2025 Formula COVID -19 vaccine feasible to implement among \npersons ≥6 months of age? \n• Is the 2024 – 2025 Formula COVID -19 vaccine program sustainable? \n• Are there barriers that are likely to limit the feasibility of implementing the \n2024 – 2025 Formula COVID -19 vaccine or require considerations when \nimplementing it? \n• Is access to the 2024 – 2025 Formula COVID -19 vaccine an important \nconcern? \no o o o o  o Yes   No Probably no Probably yes  Varies Don’t know \nEtR Domain: \nResource Use \n \n   Incremental cost -effectiveness ratios, societal \nperspective, per 1000 people -preliminary estimates \nQALY: quality -adjusted life year 75 \nDomain Equity Question: \nIs the intervention a reasonable and efficient allocation of resources \nacross all populations? \n \n  \n          \n          \n             \n    Scenario analysis: probability of hospitalization, \nICER ($/QALY) -preliminary estimates \n*Base case probability of h ospitalization: 5-11 years: 0 .000133; 12-17 years: 0.000181; 18 -49 years: 0.000443; 50 -64 years: 0.001550; 65+\nyears 0.007900\n**Adjusted risk of hospitalization for underlying condition: chronic obstructive pulmonary disease: 0.9, history of stroke: 0 .9, coronary artery\ndisease: 1.3, asthma: 1.4, hypertension: 2.8, obesity: 2.9, diabetes: 3.2, chronic kidney disease: 4.0, severe obesity: 4.4. Ko et al 2021.\nICER : incremental cost-effectiveness ratio; QALY: Quality -adjusted life year\n77 \n   \n   \n  \n  \n  \n \n \n \n \n  \n  \n Summary \nResource Use \n• Base case ICERs ranged from $23,308 in adults aged ≥65 years to $212,225 in adults aged 18 -49 years \n• Cost -effectiveness estimates in those ages ≥65 years were robust to input changes across plausible \nranges \n• Cost -effectiveness estimates in those 18 -64 years were sensitive to changes in inputs \n-ICERs are more favorable for higher vaccine impact, higher risk of hospitalization, higher quality of \nlife impact for symptomatic illness and lower vaccine dose cost \n• Cost -effectiveness estimates for those 5 -17 years were very sensitive to changes in inputs \n-ICERs are more favorable for higher vaccine impact, higher risk of hospitalization, higher quality of \nlife impact, higher probability of symptomatic illness and lower vaccine dose cost \n• COVID -19 vaccination is most cost -effective in older adults in which disease burden is highest \ncompared to younger adults \n• COVID -19 vaccination is likely more cost -effective in populations with risk factors, such as underlying \nconditions, which increase their probability of hospitalization due to COVID -19 \n• ICERs would be more favorable in younger age groups if the cost of vaccination was lower \nICER: incremental cost -effectiveness ratio 78 \n     \n \n  \n  \n  Resource Use  \nIs the 2024 – 2025 Formula COVID -19 vaccine in persons ≥6 months of age a \nreasonable and efficient allocation of resources? \n• \n• What is the cost -effectiveness of the 2024 – 2025 Formula COVID -19 \nvaccine? \nHow does the cost -effectiveness of the 2024 – 2025 Formula COVID -19 \nvaccine change in response to changes in context, assumptions, etc.? \no No o o o o o Probably no  Probably yes  Yes  Varies  Don’t know \nMajority opinion Minority opinion \nSummary and Work Group Interpretations \n   \n  \n   \n \n   \n \n   \n  \n \n    \n Work Group Interpretation \n• COVID -19 burden is currently lower than at previous points in the pandemic, however there are still \nthousands of hospitalizations and hundreds of deaths each week \n• People ages 5 – 49 years had the lowest hospitalization rates compared to other age groups \n-Severe outcomes occur in the youngest ages, including in children with no underlying medical \nconditions \n• Additional studies are needed to understand the VSD statistical signals seen for the 2023 -\n2024 COVID -19 vaccine \n-The increased rate of GBS following Pfizer COVID -19 vaccine among people aged ≥65 years may \nor may not represent a true risk. If it is a true risk, the burden of disease in this age group \nis such that the benefit of vaccination still outweighs the risk \n-The VSD statistical signals for ischemic stroke after mRNA COVID -19 vaccines during the 2023 -\n2024 season do not provide sufficient evidence to conclude that there is a safety concern and \na follow up VSD study is in progress \nVSD: Vaccine Safety Datalink | GBS: Guillain -Barre Syndrome 81 \n  \n \n  \n \n  \n  \n Work Group Interpretation (cont.) \n• 2023 -2024 COVID -19 vaccine coverage was low, particularly in children \n-Provider recommendation may encourage greater COVID -19 vaccine uptake \n-Would be important to understand why providers are not recommending vaccine, \nin addition to continuing to address inequities in vaccine access \n• High vaccine cost and decreased disease burden has resulted in less \nfavorable ICERs for younger age groups \n-The Work Group expressed concern about current ICERs for those <50 years \n-The Work Group noted that while the burden of disease in pediatric age \ngroups supported recommending COVID -19 vaccine in these age groups, the high \ncost of vaccine was a concern \n-ICERs in pediatric age groups are sensitive to changes in parameter \ninputs (i.e., uncertain) and are still considered preliminary \nICER: incremental cost -effectiveness ratio 82 \n      \n \n \n  \n \n \n   \n  \n  \n    \n   \n             Work Group Interpretation: \nConsiderations for Universal Recommendation \n• Work Group began deliberations considering both universal and non -universal policy options, but \nnon-universal options had significant implementation challenges \n-Risk based recommendations would not allow access to COVID -19 vaccines for those not in a \ndefined risk group \n• The current list of conditions that increase risk of severe illness due to COVID -191 is \nextensive and includes the majority of the US adult population2 \n• There are no groups without a risk of severe illness \n-Shared clinical decision (SCDM) making would create barriers to vaccination , may not effectively \ntarget those at highest risk , and would likely increase inequities in vaccine access \n-COVID -19 epidemiology remains uncertain and universal recommendations would need to be \nconsidered if there was an unexpected increase in burden following a risk -based or SCDM decision \n• COVID -19 disease burden remains substantial, and consistent recommendations may increase \ncoverage over time \n1. https://www.cdc.gov/coronavirus/2019 -ncov/hcp/clinical -care/underlyingconditions.html \n2. Overweight and obesity are considered conditions with conclusive or suggestive evidence of increasing risk and have a combine d prevalence >70%. National Health Statistics Reports; \nhttps://stacks.cdc.gov/view/cdc/106273 83 \n \n \n \n \n \n Summary of Work Group Interpretation \n• Benefits of COVID -19 vaccination vary by age and risk status \n-Under a universal recommendation, 2024 -2025 COVID -19 vaccines will be \navailable to all persons ages ≥6 months \n-Additional implementation efforts should be targeted toward those that will \nreceive the most benefit from COVID -19 vaccination, including people ≥65 years 1 \nold, people with underlying conditions1 including immunocompromise, and \npregnant people to protect themselves and their infants​\n• The Work Group will continue to evaluate COVID -19 vaccine policy, including the \nneed for a universal recommendation, particularly as COVID -19 epidemiology \ncontinues to change \n1. https://www.cdc.gov/coronavirus/2019 -ncov/hcp/clinical -care/underlyingconditions.html 84 \n   \n  \n \n \n  \n   \n   \n  \n  ​​​\n      \n  ​​​EtR Domain​​​ ​​Question​ Work Group Judgments \nPublic Health Problem​​​Is COVID -19 disease among persons ≥6 months of age of public health \nimportance? Yes \nHow substantial are the desirable anticipated effects? Moderate / Large \nBenefits and Harms How substantial are the undesirable anticipated effects? Small \nDo the desirable effects outweigh the undesirable effects? Favors intervention \nDo persons ≥6 months of age feel that the desirable effects are large \nrelative to undesirable effects? Varies \nValues​​​Is there important uncertainty about, or variability in, how persons ≥6 \nmonths of age value the main outcomes? Probably important uncertainty or \nvariability \nAcceptability​​​Would recommending a dose of the 2024 -2025 Formula COVID -19 \nvaccine for persons ≥6 months of age be acceptable to key stakeholders? Varies \nFeasibility​​​Is the 2024 -2025 Formula COVID -19 vaccine feasible to implement \namong persons ≥6 months of age? Probably yes / Varies \nResource Use​Is the 2024 -2025 Formula COVID -19 vaccine in persons ≥6 months of age \na reasonable and efficient allocation of resources? Probably yes \n85 \n  \n  \n \n  \n  \n \n  \n \n  \n \n \n Evidence to Recommendations Framework \nSummary: Work Group Interpretations \nUndesirable Undesirable The balance \nbetween Desirable Desirable There is \nBalance of \nconsequences consequences \nclearly outweigh \ndesirable \nconsequences consequences \nprobably \noutweigh \ndesirable desirable and \nundesirable \nconsequences \nis closely consequences \nprobably \noutweigh \nundesirable consequences \nclearly \noutweigh \nundesirable insufficient \nevidence to \ndetermine the \nbalance of \nin most settings consequences \nin most settings balanced or \nuncertain consequences \nin most settings consequences \nin most settings consequences \nMinority opinion Majority opinion 86 \n Evidence to Recommendations Framework \nSummary: Work Group Interpretations \nWe recommend the \nType of We do not recommend intervention for individuals We recommend the \nrecommendation the intervention based on shared clinical intervention \ndecision -making \n87 \n  ACIP Voting Language \nACIP recommends 2024 -2025  COVID-19 vaccines as authorized \nor approved by FDA in persons ≥6 months of age \nFDA: Food and Drug Administration 88 \n \n \n \n \n \n  \n   \n \n   \n Acknowledgements \n• Megan Wallace \n• Monica Godfrey \n• Danielle Moulia \n• Katherine Fleming -Dutra \n• Ruth Link -Gelles \n• Sarah Meyer \n• Elisha Hall \n• Jennifer Kriss \n• Kayla Calhoun \n• Kevin Chatham -Stephens \n• Susan Goldstein \n• Mary Chamberland \n• JoEllen Wolicki \n• Lauren Roper \n• Karen Broder • Evelyn Twentyman \n• Angela Campbell \n• Sharon Saydah \n• Matthew Oster \n• Sierra Scarbrough \n• Natalie Thornburg \n• Jefferson Jones \n• Dave Wentworth \n• Aron Hall \n• COVID -NET \n• University of Michigan COVID -19 Vaccination Modeling Team \n• Immunization Safety Office \n• Immunization Services Division \n• Coronavirus and other Respiratory Viruses Division \n• National Center for Immunization and Respiratory Diseases \n89 \n \n   \n    \n Thank you \nFor more information, contact CDC \n1-800-CDC-INFO (232 -4636) \nTTY: 1 -888-232-6348  cdc.gov \nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position \nof the U.S. Centers for Disease Control and Prevention. \n\nGRADE \n  \n​\n \n \n \n \n  \n \n  \n     \n         Outcomes and importance, and data sources \nOutcome Importancea Data sources \nBenefits \nMedically -attended COVID -\n19 (ED/UC visits) Critical Observational studies of vaccine effectiveness in adults/adolescents and \nabsolute vaccine effectiveness in pediatrics \nHospitalization due to COVID -19​ Critical Observational studies of vaccine effectiveness \nDeath due to COVID -19 Important Observational studies of vaccine effectiveness \nPost -COVID conditions Important Observational studies of vaccine effectiveness \nMIS-C (pediatric only) Important Observational studies of vaccine effectiveness \nHarms \nSpecified serious adverse events​ \n(SAEs) (myocarditis/pericarditis \nand anaphylaxis) Critical Safety surveillance for pre -specified SAEs \nED/UC: emergency department/urgent care; MIS -C: multisystem inflammatory syndrome in children; \na. Three options: Critical; Important but not critical; Not important for decision making \n92 \n   Evidence retrieval \nRecords identified  from \nWHO/IVAC  literature review* \n(n = 310) Additional records identified  through  \nother sources \n(n = 3)  \nRecords screened \n(n = 313) \nRecords assessed  for\neligibility \n(n =2 0)  \nRecords  included  in e vidence \nsynthesis  (n =  16) \n13  vaccine effectiveness  studies \n3 safety surveillance  studies Records excluded  from initial review \n(n  =  293) \n211  different country \n31  different outcome \n51  different study period \nFull-text articles excluded \n(n = 4) \n2  different comparator \n2 different study period \n*See https://view -hub.org/resources ; 5/10/2024 cutoff date 93 \n           \n             \n     \n \n \n  \n \n \n \n   \n \n   \n \n \n \n Evidence retrieval for vaccine effectiveness (VE) data \n▪Inclusion Criteria for IVAC systematic review* ▪Additional criteria for GRADE review \n– Published or preprint study with adequate – Studies relevant to PICO question components – \nscientific details population, intervention, comparator, and \noutcomes – Includes group with and without infection or \ndisease outcome – Studies set in the US \n– Laboratory confirmed outcome† – Study period after September 2, 2022 \n– Vaccination status confirmed in ≥90% – Vaccines with updated formulation (i.e., bivalent \nor 2023 -2024 vaccine) – Studies assess one vaccine or pooled COVID -19 \nvaccines – Included studies of general population and \nspecial populations (e.g., elderly) – Includes participants who did or did not receive a \nCOVID -19 vaccine§ \n– Vaccine effectiveness estimate includes \nconfidence intervals if possible¶ \nArticles were eligible for inclusion if published before 5/10/24. *Criteria included in the ongoing systematic review condu cted by the International Vaccine Access Center and the World Health Organization \n(see https://view -hub.org/resources ).  † Estimates of effectiveness against progression from infection disease are excluded § Comparison group is not modelled or historical ¶ Estimate accounts for \nconfounding or statement that adjustment had no effect on estimate 94 \n \n \n \n \n     Evidence retrieval \n• Observational studies for benefits (vaccine effectiveness) \n-Peer reviewed and preprint articles from IVAC systematic reviewa \n-Restricted to PICO defined population, intervention, comparison, and outcome \n• Safety surveillance for pre -specified serious adverse events for harms \n-Data on established safety concerns identified by vaccine safety surveillance systems \n-Based on input from CDC’s Immunization Safety Office (ISO) \naArticles were eligible for inclusion if published before 5/10/2024 95 \n \n \n     \n  \n  \n Observational data (n = 16) \n• 16 records identified (one or more PICO outcomes) \n• Assessed risk of bias using Newcastle -Ottawa Scale (9 -point scale) \n-For cohort studies: Selection of cohorts, Comparability of cohorts, Assessment of \noutcome \n-For case -control or test -negative design studies: Selection of cases and controls, \nComparability of cases and controls, Ascertainment of exposure \n• Two reviewers assessed each study for each outcome \n• Serious limitations identified by score <7 \n96 \n \n \n \n  \n Pooling vaccine effectiveness estimates \n• For each outcome, assessed body of evidence for suitability for pooling \n-Most representative study selected if multiple studies in same population \n-If the outcomes were measured at multiple timepoints, longest follow -up time \nwas taken \n• Vaccine effectiveness comparisons included an updated dose (either \nbivalent or 2023 -2024 formulation) compared to no updated dose (may \ninclude people who received any number of doses of prior formulations and \nunvaccinated, definitions varies by included study) \n• Meta -analyses conducted \n• Estimates evaluated for heterogeneity \n• Resulting pooled estimates summarize real -world data available at time of \nGRADE analysis \n97 \n  \n  \n \n \n \n \n Determining the GRADE certainty assessment \n▪Initial evidence type (certainty level) determined by study design \n– Initial evidence high certainty : A body of evidence from randomized controlled \ntrials \n– Initial evidence low certainty : A body of evidence from observational studies \n▪Evidence type may be downgraded due to risk of bias, inconsistency, indirectness, \nand imprecision. Evidence type may be upgraded or downgraded due to other \nconsiderations including publication bias or indications of dose -response gradient, \nlarge or very large magnitude of effect, and opposing residual confounding. \n▪Final evidence type may range from high certainty to very low certainty \n98 \nAdolescents and adults \n \n   \n     \n    \n   \n \n  \n \n \n  \n   \n  \n  \n  \n   \n     \n   \n     \n \n   \n    \n  \n \n   \n  \n  \n \n    \n \n       \n \n   \n \n     \n \n \n  \n  \n  \n    Benefits: Studies included for VE against medically -attended COVID -19 (ED/UC visits) \nStudy Population \n(age group) Method Time period Median days \nsince updated \ndose Comparison n/N  or n \ncases/N \ntotal cases n/N or n \ncontrols/N \ntotal controls Vaccine \nEffectiveness \n(95% CI) Included in \npooled estimate? \n(reason if no) \nTsenga \nJune 3, 2023 \n(Manufacturer \nfunded) General population \n(6+ yr old \nimmunocompetent & \nimmunocompromised) Retrospective cohort \n– matched 8/31/2022 – 12/31/2022 \n(18+ yr old) \n10/12/2022 -12/31/2022 \n(6 -17 yr old) 74 days BV \nvs 2 doses OMV 855/290292 2083/580584 55 (51 – 59) No – overlapping \nstudy population \nTenforde \nDecember 16, \n2022b General population \n(18+ yr old \nimmunocompetent) Test -negative 9/12/2022 – 11/18/2022 25 days BV mRNA vs \n2 doses OMV 338/2738 4359/20361 50 (44 -56) Yes \nTartof \nOctober 5, \n2023 \n(Manufacturer \nfunded) General population \n(18+ yr old \nimmunocompetent & \nimmunocompromised Test -negative 8/31/2022 -4/15/2023 77 days Pfizer BV compared \nto at least two doses \nOMV 10249 cases 53317 controls 35 (30 -40) Yes \nAckerson \nApril 4, 2024 \n(Manufacturer \nfunded) General population \n(18+ yr old \nimmunocompetent & \nimmunocompromised) Test -negative 9/1/2022 – 6/30/2023 Half of \nBA.4/BA.5 14 -60 \ndays Moderna BV \ncompared to at least \ntwo OMV BA.4/BA.5: \n218/1930 BA.4/BA.5: \n1190/5254 BA.4/BA.5: 58 \n(50 – 65) Yes \nHalf of XBB 60 -\n180 days XBB: \n343/1307 XBB: \n1113/3837 XBB: \n26 (13 – 36) \nDeCuir \nFebruary 29, \n2024 General population \n(18+ yr old \nimmunocompetent) Test -negative 9/25/2023 -1/9/2024 44 days 2023 -2024 dose \ncompared to no \nupdated dose 1297/17229 13378/111596 47 (44 -50) Yes \nCaffrey April \n7, 2024a \n(Manufacturer \nfunded) VA beneficiaries \n(immunocompetent & \nimmunocompromised) Test negative 1/25/2024 -1/31/2024 76 days 2023 -2024 dose \nPfizer compared to \nno updated dose Cases and controls: 61976 39 (33 -45) Yes \nED/UC: emergency department/urgent care; VE: vaccine effectiveness; CI: confidence interval; BV: bivalent; OMV: original mono valent \na. Pre-print article \nb. Reprint date March 17, 2023 100 \n \n \n \n   \n  \n  \n   \n     Benefits: Sensitivity analyses for VE against medically -\nattended COVID -19 (ED/UC visits) \nSensitivity analysis Number of studies VE (95% CI) \nOverall estimate 5 43 (30, 54) \nPublished studies only 4 44 (27, 57) \nNon -manufacturer -funded studies only 2 48 (30, 61) \nBivalent dose studies only 3 43 (16, 62) \n2023 -2024 dose studies only 2 45 (42, 47) \nED/UC: emergency department/urgent care; VE: vaccine effectiveness; CI: confidence interval \n101 \n \n \n       \n  \n   \n   \n    \n \n \n          \n \n       \n          -Benefits: Evidence table for VE against m edically -\nattended COVID -19 (ED/UC visits) \nCertainty assessment № of patients Effect \nCertainty Importance № of \nstudies Study \ndesign Risk of \nbias Inconsistency Indirectness Imprecision Other \nconsiderations Updated \nCOVID 19 \nvaccine No updated \nvaccine Vaccine \nEffectiveness \n(95% CI) \n5a Obsb,c not \nseriousd not serious not seriouse not serious none 27478 cases/190528 controls \n61976 cases and controls 43 \n(30 to 54)f Low CRITICAL \nED/UC: emergency department/urgent care ; VE: vaccine effectiveness; CI: confidence interval \na. Six studies were available in the body of evidence. One excluded because the study population was already represented. \nb. The body of evidence includes preprints \nc. The body of evidence includes manufacturer -funded studies \nd. Two studies contained data only for Pfizer COVID -19 vaccine and one study contained data only for Moderna COVID -19 vaccine. This was deemed unlikely to lead to a substantial \nrisk bias in the magnitude of effect. \ne. Although I2 value was high (90%), no serious concern for inconsistency was present because all studies showed consistent magnitudes of ef fect at similar time points post updated \ndose \nf. Pooled VE based on a random effects meta -analysis, using adjusted vaccine effectiveness estimates on a log scale. \n102 \n   Benefits: Certainty assessment for VE against \nmedically -attended COVID -19 (ED/UC visits) \n▪Observational Studies (n=5) \n▪Pooled vaccine effectiveness 43% (95% CI: 30 to 54) \n▪No serious concerns in certainty assessment. \n▪Final certainty assessment: Low certainty \nED/UC: emergency department/urgent care; CI: confidence interval 103 \n  \n      \n \n   \n \n    \n   \n     \n    \n  \n   \n    \n  \n  \n      \n   \n  \n  \n  Benefits: Cohort studies included for VE against \nhospitalization due to COVID -19 \nStudy Population \n(age group) Method Time period Median days \nsince \nupdated \ndose Comparison n/N n/N VE (95% CI) Included in pooled \nestimate? \n(reason if no) \nLin February \n23, 2023 General population \n(12+ yr old \nimmunocompetent & \nimmunocompromised) Retrospective \ncohort 9/1/2022 – 12/8/2022 - BV \nvs \n2 doses OMV - -59 (44 – 70) No \n(study population \noverlapped with another \nstudy) \nLin \nMay 11, 2023 General population \n(12+ yr old \nimmunocompetent & \nimmunocompromised) Retrospective \ncohort 9/1/2022 – 2/10/2023 Maximum: 105 \ndays BV \nvs \n2 dose OMV 253/127982 1955/50265509 40 (26 – 51) Yes \nTseng \nJune 3, 2023a, \nb General population \n(6+ yr old \nimmunocompetent & \nimmunocompromised) Retrospective \ncohort – \nmatched 8/31/2022 – 12/31/2022 \n(18+) \n10/12/2022 -12/31/2022 \n(6-17 yr old) 74 days Moderna BV \nvs \n2 dose OMV 160/290292 646/580584 70 (64 – 75) No (study population \noverlapped with another \nstudy) \nParitala \nDecember 4, \n2023 General population \n(12+ yr old \nimmunocompetent & \nimmunocompromised) Retrospective \ncohort 9/1/2022 Maximum: 200 \ndays BV compared \nvs 1 fewer \ndose 371/215576 1009/539191 22 (0 – 49) Yes \nVE: vaccine effectiveness; CI: confidence intervals; BV: bivalent; OMV: original monovalent \na. Pre-print article \nb. Manufacturer funded study \n104 \n    \n           \n  \n  \n   \n \n  \n    \n  \n  \n \n  \n \n  \n        \n        \n   \n \n   \n \n   \n   \n \n \n  \n    \n       \n  \n  \n   \n   \n  \n   \n \n  \n    \n     \n     Benefits: Case control studies included for VE against hospitalization due to COVID -19 \nStudy Population \n(age group) Method Time period \n(predominant \nvariant) Median time \nsince \nupdated dose Comparison Vaccinated \ncases, no./total \nno. Vaccinated \ncontrols \nno/total no. VE (95% CI) Included in pooled \nestimate? \n(reason if no) \nSurie \nMay 26, 2023a General population \n(65+ yr old immunocompetent) Test -negative 9/8/2023 – 4/1/2023 34 days BV (7 -59 days earlier) \nvs 2 OMV 61/844 175/1059 60 (45 – 71) \nNo (overlapping with another \nstudy) 89 days BV (60 -119 days \nearlier) vs 2 OMV 105/888 183/1067 35 (14 – 51) \n141 days BV (120 -176 days \nearlier) vs 2 OMV 73/856 92/976 17 (-21 – 42) \nTenforde \nDec 16, 2022b General population \n(18+ yr old immunocompetent) Test -negative 9/13/2022 -11/18/2022 23 days BV \nvs \n2 dose OMV 56/500 444/4933 48 (30 – 62) No (overlapping with another \nstudy) \nLink-Gelles \nMay 26, 2023 General population (18+ yr old \nimmunocompetent) Test -negative 9/13/2022 -4/21/2023 34 days BV (7 -59 days earlier) \nvs 2 OMV 327/4315 4530/37811 62 (57 – 67)c \nYes 87 days BV (60 -119 days \nearlier) vs 2 OMV 486/4474 4705/37986 47 (41 – 53) c \n144 days BV (120 -176 days \nearlier) vs 2 OMV 315/4303 4303/36276 24 (12 – 33) c \nTartof \nOct 5, 2023c General population \n(18+ yr old immunocompetent \n& immunocompromised) Test -negative 8/31/2022 -4/15/2023 77 days Pfizer BV vs ≥ 2 \nmRNA OMV 169/1457 1905/11101 39 (28 -49) Yes \nAckerson \nApril 4, 2024c General population \n(18+ yr old immunocompetent \n& immunocompromised) Test -negative 9/1/2022 – 6/30/2023 Half of \nBA.4/BA.5 14 -60 \ndays Moderna BV vs ≥ 2 \nmRNA OMV BA.4/BA.5: 24/235 BA.4/BA.5: \n196/581 BA.4/BA.5: 67 (44 – \n81) Yes \nHalf of XBB 60 -\n180 days XBB: 40/172 XBB: 209/427 XBB: 60 (37 – 75) \nDeCuir January \n9,2024 General population \n(18+ yr old immunocompetent) Test -negative 9/8/2022 -8/31/2023 53  days BV mRNA (7 -89 days \nafter) vs 2 OMV 184/1995 463/2843 48 (36 – 57) \nYes \n133 days BV mRNA (90 -179 \ndays after) \nvs 2 OMV 269/2080 376/2756 17 (-1 – 31) \nDeCuir , \nFebruary 29, \n2024 General population \n(18+ yr old immunocompetent) Test -negative 9/21/2023 -1/9/2024 42 days \n2023 -2024  dose vs \nno updated dose 395/4589 4199/32914 52 (47 – 57) \nYes \nTest -negative 9/21/2023 -1/31/2024 47 days 94/1194 353/2923 43 (27 – 56) \nCaffrey \nApril 7, 2024c VA Beneficiaries (18+ yr old \nimmunocompetent & \nimmunocompromised) Test negative 1/25/2024 -1/31/2024 76 days 2023 -2024 Pfizer \ndose vs no updated \ndose Cases and controls: 24206 43 (34 – 51) Yes \nVE: vaccine effectiveness; CI: confidence interval; BV: bivalent; OMV: original monovalent \na. Updated analysis from April 19, 2023 ACIP meeting “COVID -19 vaccine effectiveness updates” b. Reprint date March 17, 2023 c . Manufacturer funded study 105 \n \n  \n  \n    \n   \n   \n   Benefits: Sensitivity analyses for VE against \nhospitalization due to COVID -19 \nSensitivity analysis Number of studies VE (95% CI) \nOverall estimate 8 43 (34, 52) \nPublished studies only 5 48 (37, 57) \nNon -manufacturer -funded studies only 5 44 (33, 53) \nTest negative design studies only 6 46 (35, 54) \nBivalent dose studies only 6 43 (31, 53) \n2023 -2024 dose studies only 2 47 (32, 59) \nVE: vaccine effectiveness; CI: confidence interval \n106 \n  \n     \n   \n  \n  \n  \n \n     \n \n \n          \n \n      \n    \n          -Benefits: Evidence table for VE against hospitalization \ndue to COVID -19 \nCertainty assessment № of patients Effect \nCertainty Importance № of \nstudies Study \ndesign Risk of \nbias Inconsistency Indirectness Imprecision Other \nconsiderations Updated COVID 19 \nvaccine No \nupdated \nvaccine Vaccine \nEffectiveness \n(95% CI) \n8a Obsb,c not \nseriousd not seriouse not serious not serious none 24878 cases 166023 controls \n24206 cases and controls 44 \n(34 to 52)g Low CRITICAL \n642/343558 exposed \n2964/50504700 unexposedf \nVE: vaccine effectiveness; CI: confidence interval \na. Six studies were available in the body of evidence. Two were excluded because the study population was already represented. \nb. The body of evidence includes preprints. \nc. The body of evidence includes a manufacturer -funded study. \nd. Two studies contained data only for Pfizer mRNA COVID vaccine and one study contained data only for mRNA Moderna vaccine. Thi s was deemed unlikely to lead to a substantial \nrisk bias in the magnitude of effect. \ne. Although I2 value was high ( 87%), no serious concern for inconsistency was present because all studies showed consistent magnitudes of effect at similar ti me points post bivalent \ndose. \nf. Measurement of outcomes differed by study (COVID -19 was not necessarily confirmed as the cause of hospitalizations), but this wa s deemed not serious. \ng. Pooled VE based on a random effects meta -analysis, using adjusted vaccine effectiveness estimates on a log scale. \n107 \n  Benefits: Certainty assessment for VE against \nhospitalization due to COVID -19 \n▪Observational Studies (n=8) \n▪Pooled relative vaccine effectiveness 44% (95% CI: 34 to 52) \n▪No serious concerns in certainty assessment. \n▪Final certainty assessment: Low certainty \nCI: confidence interval 108 \n       \n \n  \n   \n \n    \n  \n  \n    \n   \n    \n   \n    \n \n   \n   \n     \n \n  Benefits: Studies included for VE against death due to \nCOVID -19 \nStudy Population (Age \ngroup) Method Time period (predominant \nvariant) Median days \nsince \nupdated \ndose Comparison n/N n/N Vaccine \nEffectiveness \n(95% CI) Included in pooled \nestimate? \n(reason if no) \nTsenga, b \nJune 3, \n2023 General population \n(6+ yr old \nimmunocompetent & \nimmunocompromised) Retrospective \ncohort – matched 8/31/2022 – 12/31/2022 (18+) \n10/12/2022 -12/31/2022 \n(6-17 yr old) 74 days Moderna BV \nvs \n2 dose OMV 10/290292 59/580584 82 (63 – 91) No (overlap with \nanother study) \nLin \nMay 11, \n2023 General population \n(12+ yr old \nimmunocompetent & \nimmunocompromised) Retrospective \ncohort 9/1/2022 – 2/10/2023 Maximum: 105 \ndays BV \nvs \n2 dose OMV 79/1279802 788/5026509 44 (9 – 65) Yes \nParitala , General population Retrospective 9/1/2022 – 6/15/2023 Maximum: BV vs 1 fewer dose 59/215576 167/539191 18 (0 -56) Yes \nDecember (12+ yr old cohort 112 days \n4, 2023 immunocompetent & \nimmunocompromised) \nAckerson \nApril 4, \n2024b General population \n(18+ yr old \nimmunocompetent & \nimmunocompromised) Test -negative 9/1/2022 – 6/30/2023 Half of \nBA.4/BA.5 14 -\n60 days Moderna BV \ncompared vs at \nleast two OMV BA.4/BA.5: 2/15 BA.4/BA.5: \n13/38 BA.4/BA.5: 53 (-\n84 – 97) Yes \nHalf of XBB 60 -\n180 days XBB: 4/10 XBB: 17/25 XBB: 32 ( -84 – \n94) \nVE: vaccine effectiveness; CI: confidence intervals; BV: bivalent; OMV: original monovalent \na. Pre-print article \nb. Manufacturer funded study \n109 \n  \n \n   \n  \n   Benefits: Sensitivity analyses for VE against death due \nto COVID -19 \nSensitivity analysis Number of studies rVE (95% CI) \nOverall estimate 3 23 (8, 36) \nPublished studies only 2 43 (23, 57) \nNon -manufacturer -funded studies only 2 22 (7, 35) \nVE: vaccine effectiveness; CI: confidence interval \n110 \n  \n \n \n       \n             \n       \n  \n \n \n  -Benefits: Evidence table for VE against death due to \nCOVID -19 \nCertainty assessment № of patients Effect \nCertainty Importance № of \nstudies Study \ndesign Risk of \nbias Inconsistency Indirectness Imprecision Other \nconsiderations Updated COVID 19 \nvaccine No \nupdated \nvaccine Vaccine \neffectiveness \n(95% CI) \n3 Obsa,b not not serious not serious not serious none 1130/343558 exposed 23 Low IMPORTANT \nseriousc 955/50504700 unexposed (8 to 36)d \n35 cases/63 controls \nVE: vaccine effectiveness; CI: confidence interval \na. The body of evidence includes a preprint. \nb. The body of evidence includes a manufacturer -funded study. \nc. One study contained data only for Moderna COVID -19 vaccine. This was deemed unlikely to lead to a substantial risk bias in the m agnitude of effect. \nd. Pooled VE based on a fixed effects meta -analysis, using adjusted vaccine effectiveness estimates on a log scale. Fixed effects m odel was used for this analysis due to imprecision of \nthe between -studies variance estimate. \n111 \n  Benefits: Certainty assessment for VE against death \ndue to COVID -19 \n▪Observational Studies (n=3) \n▪Pooled relative vaccine effectiveness was 23% (95% CI: 8 to 36) \n▪No serious concerns in certainty assessment. \n▪Final certainty assessment: Low \nCI: Confidence interval 112 \n   Benefits: VE against post -COVID conditions \n• No data captured in systematic review \n• Common reasons for exclusion \n-Review article \n-Self-reported vaccination status \n-Combines vaccine platforms \n-Not a VE study \n-Vaccination as a therapeutic (after infection) \n-Different intervention (original monovalent series) \n• Data not captured in the systematic review indicate that COVID vaccine provides some \nprotection against post -COVID conditions \n113 \n \n  \n  \n  \n Harms: Safety surveillance studies included for \nspecified serious adverse events \n▪Myocarditis/pericarditis: An analysis from the Vaccine Safety Datalink (VSD) evaluated \nchart -reviewed cases of myocarditis and pericarditis occurring among adolescents and \nadults aged 12 -39 years following an original monovalent booster dose and a bivalent \nbooster dose based on events occurring in a 7 -day risk interval after vaccination vs. a \ncomparison interval in vaccinated individuals. \n▪Anaphylaxis: An analysis from VSD evaluated chart -reviewed cases of anaphylaxis among \nall vaccinated after the original monovalent primary series persons aged 12 and older. \n114 \n      \n   \n   \n  \n  \n    \n   \n   \n \n  \n  \n  \n    \n   \n   \n   \n   \n   \n              \n   Harms: Incidence of myocarditis/pericarditis \nIncidence Rate of Verified Myocarditis/Pericarditis in the 0 to 7 Days After mRNA COVID -19 Vaccination among Persons Aged 12 – 39 Y ears by \nProduct, Age Group, Sex. \nOriginal Monovalent Booster Dose Bivalent Booster Dose \nAge group Cases/Doses \nAdministered Incidence Rate/Million Doses \n(95% CI) Cases/Doses \nAdministered Incidence Rate/Million Doses (95% CI) \nPfizer \nMale \n12-17 y - - 0/55649 0.0 (0.0 – 53.8) \n12-15 y 5/81613 61.3 (19.9 – 143.0) - -\n16-17 y 9/47874 188.0 (86.0 – 356.9) - -\n18-29 y 7/166973 41.9 (16.9 – 86.4) 1/60338 16.6 (0.4 – 92.3) \n30-39 y 3/197554 15.2 (3.1 – 44.4) 0/97171 0.0 (0.0 – 30.8) \nFemale \n12-17 y - - 0/57776 0.0 (0.0 – 51.9) \n12-15 y 0/84114 0.0 (0.0 – 35.6) - -\n16-17 y 2/55004 36.4 (4.4 – 131.3) - -\n18-29 y 1/240226 4.2 (0.1 – 23.2) 0/95162 0.0 (0.0 – 31.5) \n30-39 y 1/268412 3.7 (0.1 – 20.8) 0/133305 0.0 (0.0 – 22.5) \nModerna \nMale \n18-29 y 7/109337 64.0 (25.7 – 131.9) 0/22247 0.0 (0.0 – 134.7) \n30-39 y 1/149468 6.7 (0.2 – 37.3) 1/41820 23.9 (0.6 – 133.2) \nFemale \n18-29 y 1/156707 6.4 (0.2 – 35.6) 0/35393 0.0 (0.0 – 84.6) \n30-39 y 2/191765 10.4 (1.3 – 37.7) 0/55816 0.0 (0.0 – 53.7) \n* Primary series and monovalent booster data through August 20, 2022; source: Goddard K, et al. Incidence of Myocarditis/Pericarditis Following mRNA COVID -19 Vaccination Among Children and Younger Adults in the United States . Ann Intern \nMed. 2022;175:1169 -1771. Bivalent booster data through March 11, 2023. Data unpublished. 115 \n    \n \n   \n  \n \n      Harms: Incidence of anaphylaxis \n• Among persons 12 and older, based on events occurring in a 0 -1 day risk \ninterval after either dose of primary series vaccination, the estimated \nincidence of confirmed anaphylaxis among adolescents and adults was \n4.8 (95% CI 3.2 -6.9) per million doses of original monovalent Pfizer -\nBioNTech vaccine and 5.1 (95% CI: 3.3 -7.4) per million doses of original \nmonovalent Moderna vaccine. 1 \n-There were fewer cases of anaphylaxis post dose 2 compared with \ndose 1. \nCI: confidence interval \n1. Klein et al. Surveillance for Adverse Events After COVID -19 mRNA Vaccination. JAMA. 2021;326(14):1390 -1399 116 \nHarms: Certainty assessment for specified serious \nadverse events \n▪Observational Studies (n=2) \n▪Two rare, specified serious adverse events have been associated with \nvaccination through safety surveillance \n▪No serious concerns in certainty assessment. \n▪Final certainty assessment: Low certainty \n117 \nInfants and children \n  \n   \n \n   \n  \n        \n  \n      -Benefits: Studies included for VE against medically -\nattended COVID -19 (ED/UC visits) \nStudy Population \n(age group) Method Time period Median \nfollow up \ntime Comparison n cases/N \ntotal cases n controls/N \ntotal controls Vaccine \neffectiveness \n(95% CI) Included in \npooled \nestimate? \n(reason if no) \nLink-Gelles \nAugust \n2023 General population \n(6 mo -5 years \nimmunocompetent) Test -negative \n(VISION) 12/24/2022 – 6/17/2023 58 days BV \ncompared to \nunvaccinated 3/1331 315/29133 80 (42 -96) Yes \nED/UC: emergency department/urgent care; VE: vaccine effectiveness; CI: confidence interval; BV: bivalent \n119 \n \n  \n      \n   \n \n  \n \n    \n    -Benefits: Evidence table for VE against medically -\nattended COVID -19 (ED/UC visits) \nCertainty assessment № of patients Effect \nCertainty Importance № of \nstudies Study \ndesign Risk of \nbias Inconsistency Indirectness Imprecision Other \nconsiderations Updated COVID \n19 vaccine No updated \nvaccine Vaccine \nEefectiveness \n(95% CI) \n1 Obs not \nserious not serious not seriousa not serious none 1331 cases /29133 controls 80 \n(42 to 96) Low CRITICAL \nED/UC: emergency department/urgent care; VE: vaccine effectiveness; CI: confidence interval \na. Study population only included children aged 6 months – 5 years. This was deemed insufficient to downgrade for indirectness. \n120 \n     Benefits: Certainty assessment for VE against \nmedically -attended COVID -19 (ED/UC visits) \n▪Observational Studies (n=1) \n▪Absolute vaccine effectiveness 80% (95% CI: 42 to 96) \n▪No serious concerns in certainty assessment. \n▪Final certainty assessment: Low certainty \nED/UC: emergency department/urgent care; VE: vaccine effectiveness; CI: confidence interval 121 \n \n \n \n ​ \n  \n \n  \n   Benefits: Studies included and certainty assessment for \nVE against hospitalization and death due to COVID -19 \nNo pediatric studies captured in the evidence review on the benefits of updated COVID -\n19 vaccine against hospitalization and death, however indirect evidence of adolescent \nand adult benefit can be used to make inferences regarding pediatric benefit \nAdolescent and adult Pediatrics (with indirectness \ndowngrade) \nOutcome​ Design \n(# of studies) Vaccine effectiveness \n(95% CI) Final certainty assessment Final certainty assessment \nHospitalization due to COVID -\n19​OBS (8) 44 (34 -52) Low Very low \nDeath due to COVID -19 OBS (3) 23 (8 -36) Low Very low \nVE: vaccine effectiveness; CI: confidence interval \n122 \n  \n       \n  \n   \n  \n  \n   \n \n     \n \n \n          \n \n      \n   \n    \n          -Benefits: Evidence table for VE against hospitalization \ndue to COVID -19 \nCertainty assessment № of patients Effect \nCertainty Importance № of \nstudies Study \ndesign Risk of \nbias Inconsistency Indirectness Imprecision Other \nconsiderations Updated COVID 19 \nvaccine No \nupdated \nvaccine Vaccine \neffectiveness \n(95% CI) \n8a Obsb,c not \nseriousd not seriouse seriousf not serious none 24,878 cases 166,023 controls \n24,206 cases and controls 44 \n(34 to 0.52)h Very Low CRITICAL \n642/343,558 exposed \n2,964/50,504,700 unexposedg \nVE: vaccine effectiveness; CI: confidence interval \na. Six studies were available in the body of evidence. Two were excluded because the study population was already represented. \nb. The body of evidence includes preprints. \nc. The body of evidence includes a manufacturer -funded study. \nd. Two studies contained data only for Pfizer COVID -19 vaccine and one study contained data only for Moderna COVID -19 vaccine. This was deemed unlikely to lead to a substantial \nrisk bias in the magnitude of effect. \ne. Although I2 value was high ( 87%), no serious concern for inconsistency was present because all studies showed consistent magnitudes of effect at similar ti me points post bivalent \ndose \nf. Serious concern for indirectness was present. The vast majority of the body of evidence contained data from adolescents and a dults. \ng. Measurement of outcomes differed by study (COVID -19 was not necessarily confirmed as the cause of hospitalizations), but this wa s deemed not serious. \nh. Pooled VE based on a random effects meta -analysis, using adjusted vaccine effectiveness estimates on a log scale. \n123 \n  \n   \n    \n          \n           \n               \n   \n       \n  \n \n \n   -Benefits: Evidence table for VE against death due to \nCOVID -19 \nCertainty assessment № of patients Effect \nCertainty Importance № of \nstudies Study \ndesign Risk of \nbias Inconsistency Indirectness Imprecision Other \nconsiderations Updated COVID 19 \nvaccine No \nupdated \nvaccine Vaccine \nEffectiveness \n(95% CI) \n3 Obsa,b not not serious seriousd not serious none 1130/343,558 exposed 23 Very Low Important \nseriousc 955/50,504,700 unexposed (8 to 36)e \n35 cases/63 controls \nVE: vaccine effectiveness; CI: confidence interval \na. The body of evidence includes preprints. \nb. The body of evidence includes a manufacturer -funded study. \nc. One study contained data only for Moderna COVID -19 vaccine. This was deemed unlikely to lead to a substantial risk bias in the m agnitude of effect \nd. Serious concern for indirectness was present. The vast majority of the body of evidence contained data from adolescents and a dults. \ne. Pooled VE based on a fixed effects meta -analysis, using adjusted vaccine effectiveness estimates on a log scale. Fixed effects m odel was used for this analysis due to imprecise estimates of the \nbetween -studies variance \n124 \n \n \n \n   Benefits: VE against post -COVID conditions and MIS -C \n• No data captured in systematic review \n• Common reasons for exclusion \n-Review article \n-Self-reported vaccination status \n-Combines vaccine platforms \n-Not a VE study \n-Vaccination as a therapeutic (after infection) \n-Different intervention (original monovalent series) \n• Data not captured in the systematic review indicate that COVID vaccine \nprovides some protection against post -COVID conditions and MIS -C \nMIS-C: multisystem inflammatory syndrome in children 125 \n \n \n  \n \n Harms: Safety surveillance studies included for \nspecified serious adverse events \n▪Myocarditis/Pericarditis: An analysis from the Vaccine Safety Datalink (VSD) \namong children aged 5 -11. Rates are following an original monovalent booster \ndose. \n▪Anaphylaxis: An analysis from VSD among adolescents and adults ages 12 and \nolder. Rates are following primary series doses. \n126 \n    \n  \n    \n  \n  \n  \n     \n   \n    \n   \n    \n Harms: Incidence of myocarditis/pericarditis \n▪A single, observational study from the Vaccine Safety Datalink (VSD) evaluated chart -reviewed cases of \nmyocarditis occurring among children aged 5 -11 years following an original monovalent booster based on \nevents occurring in a 7 -day risk interval after vaccination vs. a comparison interval in vaccinated individuals. \n▪Data from VSD and the Vaccine Adverse Events Reporting System (VAERS) do not suggest an increased risk \nin children aged 6 months – 4 years \nTable. Incidence Rate of Verified Myocarditis/Pericarditis in \nthe 0 to 7 Days After mRNA COVID -19 Vaccination among \nPersons Aged 5 -11 Y ears by Age Group and Sex. \nAge \ngroup Cases/Original \nMonovalent Booster \nDoses Administered Incidence Rate/Million Doses \n(95% CI) \nPfizer \nMale \n5-11 y 0/50415 0.0 (0.0 -59.4) \nFemale \n5-11 y 0/49261 0.0 (0.0 -60.8) \n1. Goddard et al. Incidence of Myocarditis/Pericarditis Following mRNA COVID -19 Vaccination Among Children and Younger Adults in the Unite d States. Annals \nof Internal Medicine. https://www.acpjournals.org/doi/10.7326/M22 -2274 127 \n  \n    \n    \n Harms: Incidence of anaphylaxis \n• Risk of anaphylaxis in children can be indirectly inferred from the known \nrisk in persons ages 12 and older1 \n-4.8 (95% CI: 3.2 -6.9) per million doses of original monovalent Pfizer -BioNTech \n-5.1 (95% CI: 3.3 -7.4) per million doses of original monovalent Moderna \n• There were fewer cases of anaphylaxis post dose 2 compared with dose 1. \n1. Klein et al. Surveillance for Adverse Events After COVID -19 mRNA Vaccination. JAMA. 2021;326(14):1390 -1399 \n128 \n \n          \n   \n          \n          \n  \n \n        \n     \n    \n       \n     \n       \n \n     \n     \n   \n    \n   \n \n  Harms: Evidence table for serious adverse events \n(myocarditis and anaphylaxis) \nCertainty assessment № of patients Effect \nCertainty Importance № of \nstudies Study \ndesign Risk of \nbias Inconsistency Indirectness Imprecision Other \nconsiderati \nons Intervention Comparison Relative \n(95% CI) \n1 Obs not not serious seriousa not serious None • An analysis from Vaccine Safety Datalink (VSD) evaluated chart -reviewed cases Very Low CRITICAL \nserious of myocarditis occurring among children aged 5 –11 years following a bivalent \ndose. Based on events occurring in a 7 -day risk interval after vaccination vs. a \ncomparison interval in vaccinated individuals. Among children aged 5 -11 \nyears who received an updated dose of Pfizer -BioNTech, there 0 cases of \nmyocarditis among 50,415 males and 0 cases among 49,261 females (rate per \nmillion doses in men was 0 [95% CI: 0 -59.4] and women was 0 [95% CI: 0 -\n60.8]) \n• A rapid cycle analysis of data from VSD evaluated chart -reviewed cases of \nanaphylaxis among all vaccinated persons aged 12 and older. Based on events \noccurring in a 0 -1 day risk interval after vaccination, the estimated incidence \nof confirmed anaphylaxis among adolescents and adults 4.8 (95% CI 3.2 -6.9) \nper million doses of BNT162B2 and 5.1 (95% CI: 3.3 -7.4) per million doses of \nmRNA -1273. There were fewer cases of anaphylaxis post dose 2 compared \nwith dose 1.b \na. Serious concern for indirectness, as the body of evidence for myocarditis was only among children aged 5 -11 receiving a monovale nt booster and the body of evidence for anaphylaxis was among \nadults and adolescents aged 12 years and older receiving a primary series \nb. Among children ages 5 -11, the Vaccine Adverse Events Reporting System (VAERS) had 6 reports of anaphylaxis (reporting rate of 0. 4 per million doses administered) from November 3rd 2021 – \nFebruary 7th 2022. Among children ages 6 mo – 5 years, VAERS had 1 report of anaphylaxis from June 18 – August 21, 2022. 129 \n \n \n  Harms: Certainty assessment for specified serious \nadverse events \n▪Observational Studies (n=2) \n▪Two specific, rare SAE has been associated with vaccination through safety \nsurveillance \n▪Serious concern for indirectness, as the body of evidence for myocarditis was for \nan original monovalent booster and the body of evidence for anaphylaxis was \namong adults and adolescents aged 12 years and older receiving a primary \nseries \n▪Final certainty assessment: Very low certainty \nCI: Confidence interval; RR: Risk ratio 130 \n \n \n  \n  \n              \n         \n     \n     \n      \n  \n   \n  \n  \n    \n  \n    \n      \n    \n    \n   \n   \n   \n   \n   \n    \n       \n   \n    \n   \n    \n   \n     \n     \n   \n           \n        -Harms: Evidence table for serious adverse events \n(myocarditis and anaphylaxis) \nCertainty assessment № of patients Effect \nCertainty Importance № of \nstudies Study \ndesign Risk of \nbias Inconsistency Indirectness Imprecision Other \nconsiderati \nons Updated COVID 19 vaccine Comparison Relative \n(95% CI) \n1 Obs not \nserious not serious not seriousa not serious None • An analysis from Vaccine Safety Datalink (VSD) evaluated chart -reviewed cases of myocarditis occurring \namong persons aged 12 –39 years following an original monovalent booster dose and a bivalent dose. Based \non events occurring in a 7 -day risk interval after vaccination vs. a comparison interval in vaccinated \nindividuals. Among adolescents aged 12 --17 years who received a bivalent booster dose of Pfizer -\nBioNTech, there 0 cases of myocarditis among 55,549 males and 0 cases among 57,776 females (rate per \nmillion doses in men was 0 [95% CI: 0 -5] and women was 0 [95% CI: 0 -52]). Among adults aged 18 – 49 years \nthere were 2 myocarditis cases in 221,576 males, and 0 in 319,676 females. Among Pfizer -BioNTech \nrecipients, rates per million doses were: 17 (95% CI: 1 –92) in males ages 18 –29 years; 0 (95% CI: 0 –32) in \nfemales ages 18 –29 years; 0 (95% CI: 0 –31) in males ages 30 –39 years and 0 (95% CI: 0 –23) in females ages \n30–39 years. Among Moderna recipients, rates per million doses were: 0 (95% CI: 0 –135) in males ages 18 – \n29 years; 0 (95% CI: 0 –85) in females ages 18 –29 years; 24 (95% CI: 1 –133) in males ages 30 –39 years and 0 \n(95% CI: 0 –54) in females ages 30 –39 years. Among adolescents ages 12 -15 years who received an original \nmonovalent booster dose of Pfizer -BioNTech, there were 5 cases of myocarditis among 81,613 males and 0 \ncases among 84,114 females (rate per million doses in males was 61 [95% CI: 20 – 143] and in females was 0 \n[95% CI: 0 --36]). Among adolescents ages 16 -17 years, there were 9 cases of myocarditis among 47,874 \nmales and 2 cases among 55,004 females (rate per million doses in males was 188 [95% CI: 86 – 357] and in \nfemales was 36 [95% CI: 4 -131]) Among adults ages 18 -29 years, there were 7 cases of myocarditis among \n166,973 males and 1 case among 240,226 females (rate per million doses in males was 42 [95% CI: 17 – 86] \nand in females was 4 [95% CI: 0 -23). Among adults ages 30 -39 years, there were 3 case of myocarditis \namong 197,554 males and 1 case among 268,412 females (rate per million doses in males was 15 [95% CI: 3 \n– 44] and in females was 4 [95% CI: 0 -23). Among adults ages 18 -29 years who received an original \nmonovalent booster dose of Moderna, there were 7 cases of myocarditis among 109,337 males and 1 case \namong 156,707 females (rate per million doses in males was 64 [95% CI: 26 – 132] and in females was 6 \n[95% CI: 0 – 36]). Among adults ages 30 -39 years, there was 1 case of myocarditis among 149,468 males and \n2 cases among 191,765 females (rate per million doses in males was 7 [95% CI: 0 – 37] and in females was \n10 [95% CI: 1 -38). \n• An analysis of data from VSD evaluated chart -reviewed cases of anaphylaxis among all vaccinated persons \naged 12 and older. Based on events occurring in a 0 -1 day risk interval after vaccination, the estimated \nincidence of confirmed anaphylaxis among adolescents and adults 4.8 (95% CI 3.2 -6.9) per million doses of \nBNT162B2 and 5.1 (95% CI: 3.3 -7.4) per million doses of mRNA -1273. There were fewer cases of anaphylaxis \npost dose 2 compared with dose 1. Low CRITICAL \na. Indirectness was noted for anaphylaxis, as rates were from the primary series. Primary series rates of anaphylaxis are likely an overestimate of the rate in the current phase of COVID -19 \nafter an updated vaccine, and this was deemed not serious. 131", "summary": "National Center  for Immunization and Respiratory Diseases  Evidence to Recommendations Framework:  2024 -2025 COVID -19 Vaccines in Persons ≥6 Months of Age  Lakshmi Panagiotakopoulos, MD, MPH  ACIP Meeting  June 27, 2024             Evidence to Recommendations (EtR) Framework  Policy Question  • Should 2024 – 2025 COVID -19 vaccines be recommended for use in persons  ≥6 months of age?  • Products and ages under review for authorization or approval by FDA  include:  -Moderna COVID -19 vaccine…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/06-COVID-Panagiotakopoulos-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 131}
{"title": "07 COVID Stokely 508", "content": "COVID -19 Vaccine Implementation\nShannon Stokley, DrPH\nDeputy Director for Science Implementation\nImmunization Services Division\nNational Center for Immunizations and Respiratory Diseases (NCIRD)\nJune 2024National Center for Immunization and Respiratory Diseases\n\n2023 -2024 COVID -19 Vaccination Coverage\nPercentage of Children Ages 6 Months –17 Years Who Are Up to Date with \nthe 2023-2024 COVID-19 Vaccine, NIS-CCM and NIS-FLU\nAs of May 11, \n2024, \nvaccination \ncoverage \namong children \nwas 14.4% .\nData source, National Immunization Survey —COVID Child Module (NIS -CCM) and National Immunization Survey —Flu (NIS -Flu): \nhttps://www.cdc.gov/vaccines/imz -managers/coverage/covidvaxview/interactive/children -coverage -vaccination.html  \nCOVID -19 Vaccination Status Among Children Ages 6 Months –17 Years by \nDemographics, NIS -FLU, May 5 –May 11, 2024 (n=2,950)\nBy age group:\n• Vaccination coverage increased with \nincreasing age.\nBy race and ethnicity:\n•Vaccination coverage was highest among \nwhite, non-Hispanic children (15.2%) and \nlowest among Black, non-Hispanic \nchildren (10.9%).\nData source: National Immunization Survey – Flu Module  About the National Immunization Surveys | CDC\nCOVID -19 Vaccination Status Among Children Ages 6 Months –17 Years by \nDemographics, NIS-FLU, May 5 –May 11, 2024 (n=2,950)\nBy urbanicity:\n• Vaccination coverage was lowest in rural \nareas (8.4%).\nBy household income:\n•Vaccination coverage was highest among \nhouseholds with an income greater than \n$75k (18.0%) and lowest among \nhouseholds with an income lower than \n$75k (9.4-11.3%).\nData source: National Immunization Survey – Flu Module  About the National Immunization Surveys | CDC\nPercentage of Adults ≥18 Years Who Are Up to Date with the \n2023 -2024 COVID-19 Vaccine, NIS-ACM\nData source: https://www.cdc.gov/vaccines/imz -managers/coverage/covidvaxview/interactive/adult -coverage -vaccination.html  As of May 11, \n2024,\nvaccination \ncoverage \namong adults \nwas 22.5% .\nCOVID- 19 Vaccination Status Among Adults Age ≥18 Years by \nDemographics, NIS-ACM, April 28-May 25, 2024 (n=47,953)\nVaccinated with 2023-24 COVID-19 vaccine18.016.017.715.321.323.520.317.521.023.211.814.518.923.535.436.019.722.8\n0.0 20.0 40.0 60.0 80.0 100.0AI/ANMulti/OtherNH/OPIHispanicBlackWhiteAsianRuralSuburbanUrban18-2930-3940-4950-6465-7475+MaleFemale\nWeighted % (95% CI)28.921.324.821.118.216.519.625.910.722.6\n0.0 20.0 40.0 60.0 80.0 100.0Transgender/NonbinaryCisgenderGay/Lesbian/Bisexual/OtherStraightIncome unknownBelow povertyAbove poverty, <$75KAbove poverty, ≥$75KNot insuredInsured\nWeighted % (95% CI)\nAI/AN: American Indian or Alaska Native; NH/OPI: Native Hawaiian or Other Pacific Islander\nData source: National Immunization Survey – Adult COVID Module About the National Immunization Surveys | CDC\nCOVID -19 vaccination coverage among adults ≥18 years of age, \nNIS-ACM, 2022-23* and 2023- 24\nUpdated 2023 -24 COVID -19 vaccination coverage as of May 25 , 2024, is 5.1 percentage points below the 2022 -23 \nbivalent vaccine peak coverage of 27.5%.\n*\nProvider Recommendation for COVID -19 \nVaccine\n39.9%\n21.3%\n2021 August\n(7 mo. after vaccine\navailable)2024 May\n(8 mo. after updated\nvaccine available)Healthcare provider COVID -19 vaccine \nrecommendations, NIS -ACM\nRelative to 2021, \nadults reported \nfewer providers \nare recommending \nCOVID -19 \nvaccines .Percent of adults whose healthcare \nprovider recommends COVID-19 vaccine\nData source: National Immunization Survey – Adult COVID Module About the National Immunization Surveys | CDC\nPercent of Adults ≥18 Years of Age Who Reported Receiving Any Kind of \nCOVID-19 Vaccine Recommendation Since September 14, 2023, by Age Group, \nProvider Recommendation Survey, April 12-25, 2024 (N=3,004)\n66.873.4\n020406080100\nReceived any recommendationWeighted % (95% confidence interval)Age 18 -64 Age 65+\n18.240.7\n15.522.1\n020406080100\nReceived recommendation through\nconversation with provider/office\n(N=2,984)Received recommendation through\nconversation with pharmacist/pharmacy\n(N=3,010)Weighted % (95% confidence interval)Age 18 -64 Age 65+Percent of Adults ≥18 Years of Age Who Reported Receiving Active* COVID -\n19 Vaccine Recommendation Since September 14, 2023,† by Age Group, \nProvider Recommendation Survey, April 12-25, 2024\n*\"Active recommendation\" was defined as a provider, nurse/MA, pharmacist, or pharmacy technician/assistant mentioning the COVID -19 vaccine in person or during a telehealth visit, or a \npersonal phone call from a provider or pharmacist/pharmacy.  “Passive recommendation\" was defined as provider office reception staff mentioning the vaccine, seeing a sign at a provider \noffice or pharmacy, or receiving written information in person, an email, text message, automated phone call or voice message , or portal/app message from a provider office or pharmacy.\n †The denominator for these estimates includes all respondents who answered the questions and was not limited to those who repo rted visiting a provider during the respiratory virus \nseason. \nPercent of Adults ≥18 Years of Age Who Reported Receiving COVID -19 Vaccine Offer, \nReferral , or Recommendation at In -Person Visit  Since September 14, 2023 ,* by Age \nGroup, Provider Recommendation Survey, April 12 -25, 2024\n*The denominator for these estimates was restricted to those who reported they had an in person visit to a provider since September 14, 2023.23.231.4\n12.924.145.158.3\n020406080100\nReceived offer (in office)\n(N=1,984)Received referral (in office)\n(N=1,980)Received recommendation (in office)\n(N=1,987)Weighted % (95% confidence interval)Age 18 -64 Age 65+\n41.641.546.4\n41.440.439.2\n33.3 31.030.7\n14.717.3 16.4\n13.319.3 19.127.232.0\n22.2\n020406080100\nProtects me and loved ones Addressed concerns Negative effects of getting COVID -19\nEspecially important for you Personal/anecdotal experience None of the aboveWeighted % (95% confidence interval)Provider (N=531) Nurse/MA (N=265) Pharmacist (N=258)Topics Mentioned When Discussing Updated COVID -19 Vaccine with \nProvider, Nurse/MA , or Pharmacist, Reported by Adults ≥18 Years of Age, \nProvider Recommendation Survey, April 12 -25, 2024\nData source: “Provider Recommendation Survey”. 3,041 U.S. adults ages 18 years and older surveyed April 12 -25, 2024, via NORC’s probability -based AmeriSpeak  Panel . Data were weighted \nto represent the non -institutionalized U.S. population and mitigate possible non -response bias. All responses are self -reported.\nAssociation of Provider Offer, Active* vs Passive Recommendation for COVID -19 \nVaccine Since September 14, 2023, with Vaccination Among Adults ≥18 Years of Age, \nby Age Group, Provider Recommendation Survey, April 12 -25, 2024\n*\"Active recommendation\" was defined as a provider, nurse/MA, pharmacist, or pharmacy technician/assistant mentioning the COV ID-19 vaccine in person or during a telehealth visit, or a personal phone call from \na provider or pharmacist/pharmacy.  “Passive recommendation\" was defined as provider office reception staff mentioning the vaccine, seeing a sign at a provider o ffice or pharmacy, or receiving written information \nin person, an email, text message, automated phone call or voice message, or portal/app message from a provider office or pha rmacy.\nData source: “Provider Recommendation Survey”. 3,041 U.S. adults ages 18 years and older surveyed April 12 -25, 2024, via NORC’s probability -based AmeriSpeak  Panel . Data were weighted to represent the non -\ninstitutionalized U.S. population and mitigate possible non -response bias. All responses are self -reported.46.2%\n29.1%\n20.5%\n11.3%\n0 20 40 60 80No offer or\nrecommendation\n(N=738)Not offered, received\nONLY passive rec\n(N=750)Not offered, received\nactive rec\n(N=413)Offered vaccine\nby provider\n(N=368)\nWeighted % (95% confidence interval)Age 18 -64 (N=2,269)\n51.8%\n62.5%\n46.9%\n19.7%\n0 20 40 60 80No offer or\nrecommendation\n(N=177)Not offered, received\nONLY passive rec\n(N=152)Not offered, received\nactive rec\n(N=206)Offered vaccine\nby provider\n(N=171)\nWeighted % (95% confidence interval)Age 65+ (N=706)\nFrequency of recommending COVID -19 vaccination to \neligible adult patients\n \n Most providers reported recommending the COVID -19 vaccine to adults most\nof the time or always.\n11.8%14.6%\n7.4%40.0%\n26.3%\n0%20%40%60%80%100%% of respondents selecting \nresponse option (n=433)\nNever Sometimes Half the time Most of the time Always11.7%14.0%\n8.2%40.6%\n25.4%\n0%20%40%60%80%100%% of respondents selecting \nresponse option (n=342)\nNever Sometimes Half the time Most of the time AlwaysAdults ages 18 –64 years Adults ages 65 years and older\nData source: HaPPI  Survey Collaborative, University of Iowa; RAND Corporation; CDC\nReasons reported for NOT recommending COVID -19 \nvaccine to eligible adult patients (18 –64 years )\nData source: HaPPI Survey Collaborative, University of Iowa; RAND Corporation; CDC48.0%\n36.6%\n35.4%\n22.3%\n22.0%\n16.3%\n14.9%\n14.6%\n13.9%\n10.9%\n10.6%\n9.7%\n8.9%\n8.7%\n5.9%\n5.9%\n4.5%\n1.2%0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%\nThe patient will refuse vaccination\nThey have a medical reason for not getting vaccinated\nPatients are tired of hearing about COVID-19 vaccines\nPatients are tired of hearing about vaccines in general\nOther recommended vaccines for this age group are a bigger priority for me\nRelatively high COVID-19 vaccine hesitancy for this age group in my community\nThe patient has concerns about their out-of-pocket vaccination cost\nThere isn’t enough time during a visit to discuss COVID -19 vaccines\nPatients in this age group are unlikely to experience severe COVID-19 symptoms\nRecommending COVID-19 vaccination could increase general vaccine hesitancy\nThere isn’t enough time during a visit to vaccinate\nOther\nVaccination provides insufficient additional COVID-19 protection for this age group\nIf the patient is pregnant or trying to become pregnant\nVaccination doesn’t reduce COVID -19 severity for this age group\nVaccination is unnecessary for this age group if prior COVID-19 Hx\nPatients in this age group are unlikely to get COVID-19\nThe COVID vaccine is unsafe for patients in this age group% of respondents selecting response option (n=404)\nFrequency of recommending on -site COVID -19 \nvaccination to eligible pediatric patients\nApproximately the same proportion of providers reported recommending the\nvaccine sometimes, most of the time, and always. \n16.7%25.5%\n4.9%23.8% 24.7%\n4.4%11.2%27.4%\n7.1%26.0% 24.4%\n3.6%10.4%25.8%\n6.9%27.7% 28.2%\n0.6%\n0%20%40%60%80%100%\nNever Sometimes Half the time Most of the time Always Don't see age\ngroup% of respondents selecting \nresponse option (n=365)\n6 months-4 years 5-11 years 12-17 years\nData source: HaPPI Survey Collaborative, University of Iowa; RAND Corporation; CDC\nReasons reported for NOT recommending COVID -19 \nvaccine to eligible pediatric patients\nData source: HaPPI  Survey Collaborative, University of Iowa; RAND Corporation; CDC39.1%\n37.4%\n36.8%\n36.5%\n32.8%\n22.3%\n22.3%\n21.2%\n17.1%\n15.1%\n9.9%\n9.6%\n9.3%\n7.0%\n6.7%\n5.8%\n5.5%\n2.9%0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%\nRelatively high COVID-19 vaccine hesitancy for this age group in my community\nThe parent will refuse to have their child vaccinated\nOther recommended vaccines for this age group are a bigger priority for me\nThe parent will be hesitant about having their child vaccinated\nParents are tired of hearing about COVID-19 vaccines\nThey have a medical reason for not getting vaccinated\nPatients in this age group are unlikely to experience severe COVID-19 symptoms\nParents are tired of hearing about vaccines in general\nCOVID-19 vaccine recommendation could increase general vaccine hesitancy\nThere isn’t enough time during a visit to discuss COVID -19 vaccine concerns\nThe parent has concerns about their out-of-pocket vaccination cost\nVaccination provides insufficient additional COVID-19 protection for this age group\nOther\nVaccination doesn’t reduce COVID -19 severity for this age group\nThere isn’t enough time during a visit to administer the vaccine\nVaccination is unnecessary for this age group if prior COVID-19 Hx\nPatients in this age group are unlikely to get COVID-19\nThe COVID vaccine is unsafe for patients in this age group% of respondents selecting response option (n=345)\n2024 -2025 COVID -19 Vaccine \nImplementation\nProspective 2024 COVID -19 vaccine timeline\nApr May Aug Jul Jun Jan Dec Nov Oct Sept\nWHO \nTechnical Advisory \nGroup on COVID- 19 \nVaccine Composition \nRecommendation: \nMonovalent JN.1 \nlineage (4/15- 16)ACIP votes on \nproposed \nrecommendations\n(6/26–28)*FDA \nAdvises: Monovalent JN.1\nlineage; KP .2, if feasible  Vaccine available to ship\n(Potentially mid -Aug to late -Sept \ncontingent on FDA \nauthorizations/approvals)\nProviders administer vaccine\n(Orders anticipated in offices 1-2 weeks \nafter FDA action)\n*CDC publishes MMWR policy note following ACIP and FDA action (potentially late August to late September).\n**CDC updates COVID -19 Vaccine Interim Clinical Considerations immediately following FDA action.\n•Similar to the 2023 -2024 season, CDC plans to approach the 2024 -2025 \nfall/winter respiratory season comprehensively.\n-CDC will develop and deliver clinical education materials, tools, and training to \nincrease provider knowledge.2024 -25 respiratory virus vaccine program\nGoal: To help prevent disease, disability, and \ndeath from COVID-19, influenza, RSV, and other \nrespiratory diseases.\n\n•The Affordable Care Act (ACA) requires insurers to cover most ACIP -\nrecommended vaccines without cost sharing by the next coverage year.1\n•Section 3203 of the Coronavirus Aid, Relief, and Economic Security  \n(CARES) Act expedites coverage of COVID -19 vaccines beyond that which \nis required of most preventive services.2Insurance plans will cover the 2024 -2025 COVID -19 vaccines \nimmediately\n1. 42 U.S. Code § 300gg –13 - Coverage of preventive health services. https://www.law.cornell.edu/uscode/text/42/300gg -13   \n2. FAQs about Affordable Care Act Implementation Part 50: https://www.dol.gov/sites/dolgov/files/EBSA/about -ebsa/our -activities/resource -center/faqs/aca -part -50.pdf   \n•COVID -19 vaccines are covered under Medicare without cost -sharing.\n•Most Medicaid beneficiaries have access to COVID -19 vaccines without cost -sharing.\n•Inflation Reduction Act, passed in August 2022, includes key provisions:\n-Eliminates cost -sharing for all ACIP -recommended vaccines under Medicaid and Medicare Part D \nequivalent plans \n-Expanded coverage of all ACIP -recommended vaccines without cost -sharing to adult Medicaid \nbeneficiaries\n-Guarantees that nearly 50 million Medicare beneficiaries and more than 80 million Medicaid \nbeneficiaries will have access to all vaccines recommended by ACIP without cost -sharingIndividuals with Medicare and Medicaid will also have\naccess to COVID -19 vaccines at no cost\nhttps://www.dol.gov/agencies/ebsa/about -ebsa/our -activities/resource -center/faqs/aca -part -58\nhttps://www.healthcare.gov/coronavirus/\n•Eligibility: Children 0 through 18 years of age who meet at least one of the \ncriteria:\n-Medicaid eligible\n-Uninsured, or\n-American Indian/Alaska Native, or\n-Underinsured*Eligible children can receive COVID -19 Vaccines at no cost \nthrough the Vaccines for Children (VFC) Program\n*Eligible to receive vaccine only through an enrolled Federally Qualified Health Center (FQHC), Rural Health Center (RHC) or a deputized provider under Delegation of Authority\nhttps://www.cdc.gov/vaccines/programs/vfc/providers/index.html  \n•CDC’s Bridge Access Program has provided free COVID -19 vaccines to \nadults without health insurance and adults whose insurance does not \ncover all COVID -19 vaccine costs during the 2023 -2024 season.\n•Due to the Congressional funding recissions, the Bridge Access Program \nwill sunset in August 2024, and will not be available to cover the 2024 -\n2025 COVID -19 vaccine.COVID -19 Bridge Access Program\n•Once 2024 -2025 COVID -19 vaccines become widely available, \nVaccines.gov will operate as a search tool to help people find \npharmacies near them.\n•Users must verify vaccine availability for themselves. Pharmacy contact \ninformation will be provided in the search results for that purpose, as \nwell as for users to inquire about appointments.Vaccines.gov\nFor more information, contact CDC/ATSDR\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov           www.atsdr.cdc.gov \nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention and the Agency for Toxic Substances and Disease Registry.\nThank you", "summary": "COVID -19 Vaccine Implementation Shannon Stokley, DrPH Deputy Director for Science Implementation Immunization Services Division National Center for Immunizations and Respiratory Diseases (NCIRD) June 2024National Center for Immunization and Respiratory Diseases  2023 -2024 COVID -19 Vaccination Coverage Percentage of Children Ages 6 Months –17 Years Who Are Up to Date with  the 2023-2024 COVID-19 Vaccine, NIS-CCM and NIS-FLU As of May 11,  2024,  vaccination  coverage  among children  was…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/07-COVID-Stokely-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 28}
{"title": "01 inlfuenza loehr 508", "content": "National Center for Immunization & Respiratory Diseases\nInfluenza Work Group— Introduction\nDr. Jamie Loehr (Work Group Chair)\nAdvisory Committee on Immunization Practices\nJune 27, 2024\nInfluenza Work Group\nACIP  Members\n•Jamie Loehr (Chair)\n•Denise Jamieson\n•Camille Kotton\n•Robert Schechter\n•Keipp Talbot\nEx Officio\n•Timothy Brennan (FDA)\n•Uzo Chukwuma (IHS)\n•Michael Ison (NIH)\n•Cynthia Nolletti (FDA)\n•Jo Resnick (FDA)\n•Chris Roberts (NIH)Liaison  Representatives and Consultants\n•Robert Atmar\n•Kevin Ault\n•Ed Belongia\n•Hank Bernstein\n•Thomas Boyce\n•Kris Bryant\n•Doug Campos -Outcalt\n•Sarah Coles\n•Frances Ferguson\n•Sandra Fryhofer\n•Wendy Keitel\n•Marie -Michèle  Léger\n•Susan Lett\n•Krissy Moehling•Zackary Moore\n•Rebecca Morgan\n•Jesse Papenburg\n•William Schaffner\n•Ken Schmader \n•Tamara Sheffield\n•Angela Sinilaite\n•Peter Szilagyi\n•Matthew Zahn\nCDC Lead\n•Lisa Grohskopf\n2\nCDC Participants\n•Lenee Blanton\n•Karen Broder\n•Alicia Budd\n•Jessie Chung\n•Sascha Ellington\n•Jill Ferdinands\n•Brendan Flannery\n•Andrew Kroger\n•Samantha Olson\n•David Shay\n•Tom Shimabukuro\n•Mark Tenforde\n•Tim Uyeki\n3\nInfluenza A(H5N1) in Dairy Cattle\nUpdates:\n•Influenza A(H5N1 )  Update\n⁻Dr. Vivien Dugan; Director, Influenza Division, CDC/NCIRD\n•This topic is presented for information and discussion. Is\nsue:\n•Influenza A(H5N1) has been detected in dairy cows in 12 U.S. states\n•Three human cases have been reported to date, associated with exposure to cows .\n4\nProposed Recommendations for the 2024 -25 Season\nUpdates:\n•Influenza Updates, Work Group Considerations, and Proposed Recommendations \nf\nor the 2024- 25 Influenza Season\n⁻Dr. Lisa Grohskopf, CDC/NCIRD\n•This topic includes proposed recommendations for vote.Is\nsue:\n•Influenza vaccination recommendations for the 2024 -2 5 season have been drafted.\n•The draft recommendations include acknowledgement of the 2024 -25 U .S. \ninfluenza vaccine composition.\n•New recommendations are proposed for vaccination of solid organ transplant r\necipients, based on an evidence review and Work Group discussion. \n5\nFor more information, contact CDC\n1-800- CDC- INFO (232- 4636)\nTTY:  1 -888- 232- 6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.", "summary": "National Center for Immunization & Respiratory Diseases Influenza Work Group— Introduction Dr. Jamie Loehr (Work Group Chair) Advisory Committee on Immunization Practices June 27, 2024 Influenza Work Group ACIP  Members •Jamie Loehr (Chair) •Denise Jamieson •Camille Kotton •Robert Schechter •Keipp Talbot Ex Officio •Timothy Brennan (FDA) •Uzo Chukwuma (IHS) •Michael Ison (NIH) •Cynthia Nolletti (FDA) •Jo Resnick (FDA) •Chris Roberts (NIH)Liaison  Representatives and Consultants •Robert Atmar…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/01-inlfuenza-loehr-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 6}
{"title": "02 influenza dugan 508", "content": "Highly Pathogenic \nAvian Influenza \nA(H5N1)\nVivien G. Dugan, PhD\nDirector, Influenza Division\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nJune 27, 2024\n•HPAI A(H5N1) detected in birds in 1996\n A(\nH5N1) is n ot a new threat\n•Sporadic HPAI A(H5N1) virus infections of \nmammals\n have been reported since 2003 -2004\n•A(H5N1) clade 2.3.4.4b viruses emerged in wild b\nirds in 2020 \n•29 human cases of HPAI A(H5N1) have been d\netected globally since January 2022\nU.K. (5), U.S. (4), Sp ain (2), Vietnam (2), China \n(2), Ecuador, Cambodia (11), Chile, AustraliaOverview of HPAI A(H5N1)\nAvian Influenza Communication Resources | Bird Flu | CDC2\nHuman A(H5N1) Cases Since 1997\nTechnical Report: June 2024 Highly Pathogenic Avian Influenza A(H5N1) Viruses | Bird Flu | CDC3\n\nHPAI A(H5N1) in Dairy Cattle: \nCurrent Situation and Response Updates\n4\n•USDA has confirmed A(H5N1) virus \nin\nfections of dairy herds in >100 \nfarms across 12 states\nClade 2.3.4.4b virus\nHigh levels of virus in raw milk\n•Other animal species reported in a\nssociation with infected dairy \nherds in the United States include:\nWild birds, cats, racoon, opossums\n•Wide range of infected wild bi\nrds, terrestrial and marine \nmammal species worldwideHPAI A(H5N1) in Dairy Herds\nHighly Pathogenic Avian Influenza (HPAI) Detections in Livestock ; WAHIS (woah.org)\n5\n\nA(H5N1) Human Cases\n•April 1 – Texas announced 1st human infection \nof HPAI A(H5N1) virus* \n•May 22 – Michigan announced 2nd human \ninfection of influenza A (H5)†\n•May 30 –Michigan announced 3rd human \ninfection of influenza A (H5)†\n•Adults working at dairy farms and in contact \nwith cows\n•1st and 2nd cases reported conjunctivitis only, \n3rd reported minor respiratory symptoms\n•All offered oseltamivir, mild illness and recovered without hospitalization\n•No human- to-human transmission\n* Health Alert: First Case of Novel Influenza A (H5N1) in Texas, March 2024 | Texas DSHS\n† Influenza A (H5N1) (michigan.gov)6\nA(H5N1) Human Cases – Virus Sequences to Date\n•Diagnostics: No impact to current CDC influenza diagnostic \nassay's ability to detect A(H5N1) viruses\n•Treatments: No known markers of resistance to FDA \napproved antiviral drugs (polymerase acidic inhibitor: baloxavir ; \nneuraminidase inhibitors: oseltamivir, peramivir, and zanamivir)\n•Candidate Vaccine Viruses (CVVs)\nHA of human influenza virus very closely related to two available CVVs\nCVVs expected to provide good protection against this virus\n7\n•Since March 2024, d uring the current HPAI A(H5N1) outbreak in dairy cattle, at least 690 people monitored from affected \nfarms, at least 51 tested, 3 positives (1 in TX, 2 in MI, last case detected May 30, 2024)\n•Since March 2024, public health laboratory monitoring includes testing of 30,163 specimens have been tested using a \np\nrotocol that would have detected A(H5N1) and other novel virusesSurveillance, Human Monitoring, and Testing\nHow CDC is monitoring influenza data among people to better understand the current avian influenza A (H5N1) situation | Bird Flu | CDC, Weekly U.S. Influenza Surveillance Report | CDC8\nNo indicators of unusual influenza activity in \npeople, including avian influenza A(H5N1)\n\n‘High’ Wastewater Sites and H5 Detections\nHow CDC is monitoring influenza data among people to better understand \nthe current avian influenza A (H5N1) situation | Bird Flu | CDCDeveloped Levels for Influenza \nA Virus in Wastewater\n•Influenza A Virus Level metric\n•Compare current level to levels \nat the\n same site during the \n2023- 2024 influenza season\n•Flag ≥80th percentile as “high”\n•Outreach to state/local part\nners in \"high\" areas, as \nwell as notifying state, local, and federal partners\n9Data from June 2, 2024 – June,15, 2024\nEpidemiologic Investigations\n•Health and agricultural partners at local, \nstate and federal level, and affected farms using One Health approach\n•Important public health questions\nEvidence of infection in exposed populations?\nSpectrum of illness and rate of asymptomatic \ninfections?\nTypes of exposure on farms/dairies?\nBehaviors associated with human infections or protection from infection?\n•Assess risk for symptomatic and\nasymptomatic infection and a survey to \nassess exposures\n10\n Avian Influenza Communication Resources | Bird Flu | CDC\nSummer Influenza Surveillance Priorities\n•Continued monitoring of people with recent exposure on confirmed farms\n•Facilitate detection of A(H5N1) human cases in the community through \nenhanced, national surveillance at seasonal influenza levels\nSubtyping of influenza A positive specimens, expanded specimen sources\nContinued surveillance of lab- confirmed influenza associated hospitalizations \nthrough FluSurv -NET\n•Continued follow -up for areas that flag in syndromic and wastewater data\n•Provider outreach to continue influenza testing through summer, \nparticularly for patients with recent history of relevant exposures\nCDC Strategy for Enhanced Summer 2024 Influenza Surveillance | Avian Influenza (Flu) 11\nGlobal Surveillance is Central to Prevention and Mitigation\n•Characterize human \nand z\noonotic \ninfluenza viruses\n•Contribute data for bi\nannual vaccine \ncomposition\n•Generate and e\nvaluate Candidate \nVaccine Viruses\n•147 WHO National Influenza Centers in 123 Member States (CDC Atlanta Influenza Laboratory is one)\n•7 WHO Collaborating Centers for Influenza (CDC is one)\n•12 WHO H5 Reference Laboratories\n Global Influenza Surveillance and Response System (GISRS) (who.int)12\nPublic Health Risk\n•Overall risk to the public remains low\n•Increased risk with exposure to \ninfected animals or environment \n(occupational, recreational)\n•Exposed individuals should monitor \nfor symptoms after first exposure \nand for 10 days after last exposure\nHighly Pathogenic Avian Influenza A(H5N1) Virus in Animals: Interim Recommendations for \nPrevention, Monitoring, and Public Health Investigations | Avian Influenza (Flu) (cdc.gov)\nAvian Influenza Communication Resources | Bird Flu | CDC13\nCDC’s HPAI A(H5N1) \nResponse Priorities \n•CDC leads public health activities and is \nworking closely with USDA, FDA, and \nstate and local public health agencies\n•Supporting and engaging public health and agricultural partners using a One \nHealth approach\n•Protecting human health and safety \n•Understanding risk to people from A(H5N1) viruses\n•Assessing A(H5N1) viruses for genetic \nchanges\n14Avian Influenza Communication Resources | Bird Flu | CDC\nResources from CDC\n15•Situation Updates\nCDC A(H5N1) Bird Flu Response Update | Avian Influenza (Flu)\n•Surveillance Updates\nHow CDC is monitoring influenza data among people to better \nunderstand the current avian influenza A (H5N1) situation | Avian \nInfluenza (Flu)\n•Technical Report\nTechnical Report: Highly Pathogenic Avian Influenza A(H5N1) Viruses | Avian Influenza (Flu) (cdc.gov)\n•Updated Recommendations\nHighly Pathogenic Avian Influenza A(H5N1) Virus in Animals: Interim \nRecommendations for Prevention, Monitoring, and Public Health Investigations | Bird Flu | CDC\nRecommendations for Worker Protection and Use of Personal \nProtective Equipment (PPE) to Reduce Exposure to Novel Influenza A Viruses Associated with Severe Disease in Humans\n•CDC Public Health Science Agenda\nCDC Public Health Science Agenda for Highly Pathogenic Avian \nInfluenza A(H5N1) – June 2024 | Bird Flu | CDC\nCDC A(H5N1) Bird Flu Response Update June 21, 2024 | Bird Flu | CDC\nQuestions", "summary": "Highly Pathogenic  Avian Influenza  A(H5N1) Vivien G. Dugan, PhD Director, Influenza Division National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention June 27, 2024 •HPAI A(H5N1) detected in birds in 1996  A( H5N1) is n ot a new threat •Sporadic HPAI A(H5N1) virus infections of  mammals  have been reported since 2003 -2004 •A(H5N1) clade 2.3.4.4b viruses emerged in wild b irds in 2020  •29 human cases of HPAI A(H5N1) have been d etected globally…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/02-influenza-dugan-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 16}
{"title": "03 influenza grohskopf 508", "content": "U.S. Centers for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nInfluenza Updates, Work Group Considerations, and \nProposed Recommendations for the 2024 -25 \nInfluenza Season\nLisa Grohskopf, Jill Ferdinands, and Lenee Blanton\nInfluenza Division, CDC/NCIRD\nJune 27, 2024\nJill Ferdinands\nLenee Blanton\nLindsay Trujillo\nJoanna Taliano\nAndrew Leidner\nRebecca Morgan\nDoug Campos- O utcaltAcknowledgements\n2\nU.S. Influenza vaccine composition for the 2024 -2 5 season\nBrief end- of-s eason influenza vaccine safety update\nHigher dose and adjuvanted influenza vaccines for solid organ \nt\nransplant recipients: Evidence to Recommendations (EtR) Discussion\nProposed recommendations for the 2024 -2 5 seasonOverview\n3\nInfluenza Updates\n4\nAll influenza vaccines marketed in the United States for the 2024- 2 5 season will be \ntrivalent\nThere will be no influenza B/Yamagata component, following no confirmed \nd\netections of wild -type influenza B/Yamagata viruses since March 2020\nU.S. influenza vaccine composition for 2024- 2 5 includes an update to the influenza \nA(H3N2) component:\n–AnA/V ictoria/4897/2022 (H1N1)pdm09 -like virus for egg -based vaccines \nor an A/Wisconsin/67/2022 (H1N1)pdm09 -like virus for cell and recombinant vaccines;\n–An A /Thailand/8/2022 (H3N2)- like virus for egg -based vaccines \nor an A/Massachusetts/18/2022 (H3N2) -like virus for cell and recombinant vaccines;\n–A B/Austria/1359417/2021 (B/Victoria lineage) -l ike virusU.S. Influenza Vaccine Composition for the 2024 -25 \nInfluenza Season\nVaccines and Related Biological Products Advisory Committee March 5, 2024 Meeting Announcement - 03/05/2024 | FDA 5\nImmunization Safety Office\nCenters for Disease Control and PreventionNATIONAL CENTER FOR EMERGING AND ZOONOTIC INFECTIOUS DISEASES\nEnd- of-Season Update: 2023 -2024\nInfluenza Vaccine Safety Monitoring \n•~158 million doses of influenza vaccine distributed in United States*\n•Vaccine Adverse Event Reporting System (VAERS) ( co-managed by CDC and \nFDA) \n-No new safety concerns identified for influenza vaccines\n•Vaccine Safety Datalink (VSD) ( collaboration between CDC and 13 \nintegrated healthcare organizations)\n-VSD monitors pre -s pecified outcomes using rapid cycle analysis (RCA)**\n-~4.8 million doses of influenza vaccine administered in VSD through 5/31/2024  \n-No new safety concerns identified in influenza vaccine monitoringVaccine Safety Update: 2023 -2024 Influenza Season\n12*As of March 9, 2024, Weekly Flu Vaccination Dashboard | FluVaxView | Seasonal Influenza (Flu) |\n** Outcomes monitored in VSD for influenza vaccines: acute disseminated encephalomyelitis (ADEM), anaphylaxis (case counts), Bell's palsy, \nencephalitis, Guillain- Barré syndrome, seizures, and transverse myelitis; Li et al. Post licensure surveillance of influenza vaccines in the Vaccine \nSafety Datalink in the 2013– 2014 and 2014– 2015 seasons (wiley.com)  Pharmacoepidemiol  Drug Saf. 2016 Aug;25(8):928- 34. •.\nHigher Dose and Adjuvanted Influenza Vaccines \nfor Solid Organ Transplant Recipients: EtR Discussion\nBackground\n8\nSolid Organ Transplantation in the United States\nNational Data, Organ Transplant and Procurement Network (OPTN). National data - OPTN (hrsa.gov)\nU.S. Organ Transplants Performed, 2023\nAll 46,632  (100)\nBy age group N (%)\n<18 years 1,916        (4)\n18-64 years 33,610      (72)\n≥65 years 11,104     (24)\nOrgan(s) N (%)\nKidney 27,332     (59)\nLiver 10,660    (23)\nHeart 4,545     (10)\nLung 3,026       (6)\nKidney/pancreas 812       (2)\nPancreas 102       (0.2)\nHeart/lung 54       (0.1)\n05000100001500020000250003000035000400004500050000\n2000 2002 2004 2006 2008 2010 2012 2014 2016 2018 2020 2022Total Solid Organ Transplants Performed \nin the U.S. By Year, 2000- 2023\nTransplants, n\n9\nPer ACIP recommendations, SOT recipients should receive an age-ap propriate \ninactivated or recombinant influenza vaccine (i.e., an IIV or RIV)\n–Live attenuated influenza vaccine (LAIV) is not recommended for immunocompromised populations \nImmunosuppressive regimens might contribute to diminished response to vaccines\nHigh- d ose (HD -IIV) and adjuvanted (aIIV) inactivated influenza vaccines have been \nstudied in SOT recipients\nAmerican Society for Transplantation (AST) states that high- d ose or boosted dosing \nmight be preferable post -transplant\nHD-I IV and aIIV are approved for ages ≥65 years, and might not be covered by \ninsurance when administered to persons under age 65 yearsRecommendations for Influenza Vaccination of SOT \nRecipients \nACIP , Prevention and Control of Seasonal Influenza with Vaccines, 2023 -24. https://www.cdc.gov/mmwr/volumes/72/rr/rr7202a1.htm\nDanziger -Isakov L et al, Clin Transplant 2019;33(9):e1356310\nShould high- do se inactivated, adjuvanted inactivated, and/or \nrecombinant influenza vaccines be recommended as an option for \ninfluenza vaccination of solid organ transplant recipients who are younger than the approved age indication?\n–<65 years for high -d ose and adjuvanted influenza vaccines\n–<18 years for recombinant influenza vaccine\n Policy Question\n11\nPublic Health Importance\nEtR Domain 1\n12\nThe number of transplants performed \nea\nch year, and post -transplant survival \nhave increased\n     Approximately 430,000 recipients a\nlive in 2020\n–0.1% of U.S. populationPublic Health Importance —Scope of Population\n \nMedian recipient survival (years)\nOrgan 1987 -2012 1987 -2021\nKidney 12.4 14.8\nLiver 11.6 14.6\nHeart 9.5 11.7\nLung 5.2 5.6\nPancreas 13.3 16.1\nRecipients alive, n\nOrgan June 2015 June 2020\nKidney 200,000 255,738\nLiver 74,945 98,842\nHeart 29,172 37,419\nLung 12,100 17,500\nPancreas 14,161 19,458\n*Considering recipients of the most commonly transplanted organs, \nfor whom systemic immunosuppression is generally required\nOrgan Transplant and Procurement Network (OPTN). National data - OPTN (hrsa.gov)\nRana et al, JAMA Surgery 2015; 150(3):252 -259\nFerreira et al, Digestive Diseases and Sciences 2023;68:3810 -3817  OPTN/SRTR 2015 Annual Data Report\nOPTN/SRTR 2020 Annual Data Report 2020 ADR (hrsa.gov) 13\nSOT recipients require lifelong immunosuppressive medications.\nManifestations of influenza can be more severe\n–Lower respiratory tract disease, including pneumonia, occurs in 22 -49%  of SOT \nrecipients\nIn a 5 -year cohort of SOT recipients with influenza (n=477):  \n•21% had lower respiratory tract disease on presentation\n•69% were hospitalized\n•11% admitted to an intensive care unit\n•  8% required mechanical ventilation\n•  \n3% died (all- c auses) within 30 days\n     Public Health Importance —Disease Burden\n14Mombelli et al, Exp Rev Anti- infect Ther 2020;18:103 -112\nKumar et al, Cin Infect Dis 2018;67:1322 -1329\n \nIs influenza among solid organ transplant recipients a problem of public health \nimportance?\nNo\nProbably no\nProbably yes\nYes\nVaries\nDon’t know \n     WG Judgement: Public Health Importance\n1515\nBenefits and Harms\nEtR Domain 2\n16\n Population, Intervention, Comparator, and Outcomes\nPopulation Solid organ transplant recipients aged ≥6 months\nInterventions High -dose (HD -IIV), MF59 -djuvanted (aIIV), or recombinant (RIV) trivalent or quadrivalent influenza \nvaccines\nComparator Single intramuscular dose of trivalent or quadrivalent unadjuvanted standard dose influenza vaccines\nOutcomes Primary outcomes\nBenefits:\n•Medically-attended influenza (Critical)\n•Influenza -associated hospitalization (Critical)\n•Laboratory-confirmed influenza —immunogenicity data acceptable (Important)\nHarms:\n•Transplant rejection or graft failure (Critical)\n•Neuroinflammatory conditions , e.g. GBS, ADEM (Critical)\n•Other immune -related adverse events, including new onset or exacerbation of an autoimmune \ncondition (Critical)\n17\n9 papers describing 9 studies:\n– 8 randomized; 1 cohort\nVaccines and comparisons:\n–HD- IIV3 vs. SD -IIV3    2\n–Double-dose vs. single-dose SD-IIV3  2\n–aIIV3 vs. SD - IIV3    3\n–aIIV3 vs. HD - IIV3 vs. SD -IIV4   1\n–aIIV3 (most participants, no comparator) 1\n–No papers examining RIV   \nTransplant populations:\n–Kidney  4\n–Heart  1\n–Mixed 4    (40 -80% kidney)No papers reported on medically -\na\nttended influenza, neuroinflammatory \nconditions, or immune -mediated adverse \nevents (all critical outcomes)\nOnly one pediatric study (omitted from \nm\neta-analysis/GRADE)\nCohort study excluded from GRADE g\niven small size, lack of a comparison \ngroup, and availability of randomized studies\n7 papers included in GRADEStudy Characteristics (n=9)\n18\nSummary—Benefits: aIIV3 vs SD- IIV\n19Outcome N studies\n(n participants)Pooled RR (95% CI) GRADE Certainty Importance\nInfluenza- associated hospitalization 1  (403) 2.90  (0.12, 70.71) Low Critical\nMedically -attended influenza 0 - - Critical\nLab- confirmed influenza 1  (403) 0.97  (0.43, 2.18) Moderate Important\nSeroconversion to H1N1 3  (558) 1.37  (1.09, 1.72) Low Important\nSeroconversion to H3N2 3  (558) 1.51  (1.25, 1.82) Low Important\nSeroconversion to B 3  (558) 1.64  (1.28, 2.11) Low Important\nSeroprotection to H1N1 3  (558) 1.06  (0.98, 1.14) Very low Important\nSeroprotection to H3N2 3  (558) 1.20  (1.07, 1.33) Low Important\nSeroprotection to B 3  (558) 1.17  (1.01, 1.34) Low Important\nSummary—Benefits: HD- IIV3 vs SD- IIV\n20Outcome N studies\n(n participants)Pooled RR (95% CI) GRADE Certainty Importance\nInfluenza- associated hospitalization 1  (393) 3.05  (0.12, 74.32) Low Critical\nMedically -attended influenza 0 - - Critical\nLab- confirmed influenza 2  (565) 1.09  (0.52, 2.27) Moderate Important\nSeroconversion to H1N1 2  (554) 2.46  (1.86, 3.27) Moderate Important\nSeroconversion to H3N2 2  (554) 1.67  (1.38, 2.02) Moderate Important\nSeroconversion to B 2  (554) 1.90  (1.46, 2.46) Moderate Important\nSeroprotection to H1N1 2  (554) 1.03  (0.95, 1.11) Low Important\nSeroprotection to H3N2 2  (554) 1.13  (1.01, 1.26) Moderate Important\nSeroprotection to B 2  (554) 1.22  (1.08, 1.38) Moderate Important\nSummary—Harms\n21Outcome Studies (N) Pooled RR (95% CI) GRADE Certainty Importance\naIIV3 vs SD-IIV\nGraft rejection 3  (517) 0.28  (0.06, 1.34) Moderate Critical\nNeuroinflammatory events 0 - - Critical\nOther autoimmune events 0 - - Critical\nHD-IIV3 vs SD-IIV\nGraft rejection 3  (579) 1.00  (0.32, 3.06) Moderate Critical\nNeuroinflammatory events 0 - - Critical\nOther autoimmune events 0 - - Critical\nSummary of Evidence: aIIV3 vs SD -IIV\nOutcome Importance No. studies Included in profile Favored vaccine Certainty\nBenefits\nMedically -attended influenza Critical 0 - - -\nInfluenza- associated hospitalization Critical 1 Yes Neither Low\nLaboratory -confirmed influenza Important 1 Yes Neither Moderate\nImmunogenicity (surrogate outcome)\nSeroconversion to A(H1N1) Important 3 Yes aIIV3 Low\nSeroconversion to A(H3N2) Important 3 Yes aIIV3 Low\nSeroconversion to B Important 3 Yes aIIV3 Low\nSeroprotection to A(H1N1) Important 3 Yes Neither Very Low\nSeroprotection to A(H3N2) Important 3 Yes aIIV3 Low\nSeroprotection to B Important 3 Yes aIIV3 Low\nHarmsTransplant rejection/graft failure Critical 3 Yes Neither Moderate\nNeuroinflammatory conditions Critical 0 - - -\nOther immune -mediated adverse events Critical 0 - - -\n22\nSummary of Evidence: HD -IIV3 vs SD- IIV\nOutcome Importance No. studies Included in profile Favored vaccine Certainty\nBenefits\nMedically -attended influenza Critical 0 - -\nInfluenza- associated hospitalization Critical 1 Yes Neither Low\nLaboratory -confirmed influenza Important 2 Yes Neither Moderate\nImmunogenicity (surrogate outcome)\nSeroconversion to A(H1N1) Important 3 Yes HD-IIV3 Moderate\nSeroconversion to A(H3N2) Important 3 Yes HD-IIV3 Moderate\nSeroconversion to B Important 3 Yes HD-IIV3 Moderate\nSeroprotection to A(H1N1) Important 3 Yes Neither Low\nSeroprotection to A(H3N2) Important 3 Yes HD-IIV3 Moderate\nSeroprotection to B Important 3 Yes HD-IIV3 Moderate\nHarmsTransplant rejection/graft failure Critical 3 Yes Neither Moderate\nNeuroinflammatory conditions Critical 0 - -\nOther immune -mediated adverse events Critical 0 - -\n23\nFew studies; most are small (4 of 7 have <100 participants)\nNo direct evidence of relative benefit or either HD -i iv3 or aIIV3 vs SD -IIV\n–Only indirect evidence (immunogenicity)\nVariability in timing of immunogenicity endpoints and how they are \nrep\norted\nNo information for critical outcomes of medically -a ttended influenza, \nneuroinflammatory conditions, or other immune- mediated events\n–Given study sizes, power probably not adequate\nNo evaluations of RIV\n Limitations\n24\nHow substantial are the desirable anticipated effects?\nMinimal\nSmall\nModerate\nLarge\nVaries\nDo\nn’t know \n     WG Judgement: Benefits and Harms\n25\nHow substantial are the undesirable anticipated effects?\nMinimal\nSmall\nModerate\nLarge\nVaries\nDon’t know \n     WG Judgement: Benefits and Harms\n26\nDo desirable effects outweigh undesirable effects?\nFavors intervention\nFavors comparison\nFavors both\nFavors neither\nVaries\nDon’t know \n     WG Judgement: Benefits and Harms\n27\nBenefits of the intervention \nNo studies found \nVery low\nLow\nModerate \nHigh\n    \n Harms of the intervention No studies found \nVery low\nLow\nModerate \nHighBenefits and Harms: Certainty of Evidence\n28What is the overall certainty of the evidence for the critical outcomes?\nValues and Preferences\nEtR Domain 3\n29\nNo direct evidence was identified reflecting values or preferences for specific influenza \nvac\ncine types among SOT recipients\nThere might be a healthcare provider preference for HD -II V, evidenced by the \nrecommendations of the American Society for Transplantation and various transplant programs\n Values and Preferences for Influenza Vaccine Types\nDanziger -Isakov L et al, Clin Transplant 2019;33(9):e13563\nCOVID -19 and Flu Vaccination Information for Transplant Patients - Penn Medicine30\nDoes the target population feel that the desirable effects are large relative to undesirable \neffects?\nNo\nProbably no\nProbably yes\nYes\nVaries\nDon’t know \n     WG Judgement: Values\n31\nIs there important uncertainty about or variability in how much people value the main \noutcomes?\nImportant uncertainty or variability \nProbably important uncertainty or variability\nProbably not important uncertainty or variability\nNo important uncertainty or variability\nNo known undesirable outcomes\n     WG Judgement: Values\n32\nAcceptability\nEtR Domain 4\n33\nAcceptability of a recommendation for high- d ose vaccine is possibly \nevidenced by recommendations of the AST and some transplant \nprograms for high- dose vaccine\nAcceptability might be limited among healthcare and public health \ns\nystems and insurers by need for changes in standing orders, \nimmunization information systems, and electronic medical record platforms\n Acceptability Considerations\n34\nIs the intervention acceptable to key stakeholders?\nNo\nProbably no\nProbably yes\nYes\nVaries\nDon’t know \n     WG Judgement: Acceptability\n35\nResource Use\nEtR Domain 5\n36\nNo economic analysis was conducted:\n–Population ~430,000 as of 2020 \n–Insufficient data concerning relative effectiveness of influenza vaccines in SOT populations\n–Insufficient data indicating extent to which use of these vaccines is already occurring among off -l abel \nage group SOT recipients\nHD-I IV3 and aIIV3 more costly ($73- 77) than unadjuvanted influenza vaccines ($21 -34)\n Is the Intervention a Reasonable and Efficient Allocation of \nResources?\nInfluenza Vaccine Pricing (2023 -24), CMS.gov ( https://www.cms.gov/medicare/payment/part -b-drugs/vaccine -pricing  )37\nIs the intervention a reasonable and efficient allocation of resources?\nNo\nProbably no\nProbably yes\nYes\nVaries\nDon’t know \n     WG Judgement: Resource Use\n38\nEquity\nEtR Domain 6\n39\nNo literature was found concerning use of enhanced influenza vaccines \na\nmong transplant recipients\nAmong Medicare beneficiaries aged ≥65 years in a single- se ason (2015 -16), \nBlack, Asian, and Hispanic persons were 26% to 32% less likely to receive HD-IIV3 than White persons\nA WG member noted other potential barriers for SOT recipients:\n–SOT recipients face barriers to receiving newer influenza vaccines as they are usually \ne\nxcluded from clinical trials, and there are few data for this population\n–Transplant programs with greater financial resources might be able to purchase va\nccines for their patients, whereas those less well- resourced might notEquity\nMahmud et al, Lancet Healthy Longevity 2021;2:e143 -e153\n40\nWhat would be the impact on health equity?\n\n\nReducedProbably reducedProbably no impactProbably increasedIncreased\nVaries\nDon’t know \n     WG Judgement: Equity\n41\nFeasibility\nEtR Domain 7\n42\nFactors favoring feasibility\nThe recommendation might improve \na\nccess, if more likely to be covered by \ninsurance.\nIf covered, insurance and r\neimbursement concerns should be \nminimal.\nVaccination should be easily im\nplementable in office and retail \nsettings that serve adults.\nThe vaccines are licensed and r\noutinely stocked.\n Factors not favoring feasibility\nA recommendation stating that vaccines \na\nre acceptable options (as opposed to a \npreferential recommendation) might not compel insurers to cover them.\nUse of vaccine in a new age group might r\nequire changes in standing orders, \nElectronic Medical Record programming, and immunization information systems.Feasibility\n43\nIs the intervention feasible to implement?\nNo\nProbably no\nProbably yes\nYes\nVaries\nDon’t know \n     WG Judgement: Balance of Consequences\n44\nBalance of Consequences and \nSufficiency of Information\n45\nUndesirable consequences c learly outweigh  desirable consequences in most settings\nUndesirable consequences pr obably outweigh desirable consequences in most settings\nThe balance between desirable and undesirable consequences  i s closely balanced or uncertain \nDesirable consequences pr obably outweigh undesirable consequences in most settings\nDesirable consequences c learly outweigh  undesirable consequences in most settings\nThere is insufficient evidence to determine the balance of consequences\n     WG Judgement: Balance of Consequences\n46\nIs there sufficient evidence to move forward with a recommendation\nYes\nNo\n     WG Judgement: Sufficiency of Information\n47\nProposed Recommendations\n48\nRoutine annual influenza vaccination is recommended for all persons aged \n≥\n6 months without contraindications.\n–Same as previously\nAll persons should receive an age- a ppropriate influenza vaccine (i.e., one \napproved for their age), with the following exception: solid organ transplant recipients aged 18 through 64 years on immunosuppressive medication regimens may receive either  HD -IIV3 or aIIV3 as an \nacceptable option (without a preference over other age- appropriate IIV3s \nor RIV3). Proposed Recommendations for Influenza Vaccination, \n2024 -25 (For Vote)\n49\nFor more information, contact CDC\n1-800- CDC- INFO (232 -4636)\nTTY:  1 -888 -232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention.\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\n50", "summary": "U.S. Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. Influenza Updates, Work Group Considerations, and  Proposed Recommendations for the 2024 -25  Influenza Season Lisa Grohskopf, Jill Ferdinands, and Lenee Blanton…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/03-influenza-grohskopf-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 50}
{"title": "01 Pneumococcal Loehr 508", "content": "Centers for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.\nPneumococcal Vaccines\nJune 2024, ACIP Meeting\nJune 27, 2024\nPneumococcal Vaccine Work Group Chair\nJames Loehr, MD, FAAFP\nACIP Members\n▪Jamie Loehr  (Chair)\n▪Sarah Long\n▪Robert Schechter \nEx Officio Members\n▪Lucia Lee            (FDA)\n▪Tina Mongeau   (FDA)\n▪Uzo  Chukwuma (IHS)\n▪Mamodikoe Makhene (NIH, primary)\n▪Meenu Upadhyay (NIH, alternate)\nLiaison Representatives\n▪Lynn Fisher                (AAFP)\n▪James Campbell      (AAP/COID)\n▪Jason Goldman         (ACP)\n▪David Nace                 (AGS/AMDA)\n▪Cora Hoover               (AIM, primary)▪Risa Claytor                (HRSA)\n▪James McAuley        (IDSA)\n▪Eva Wong                 (NACI)\n▪Robert Hopkins    (NFID, primary)\n▪William Schaffner     (NFID, alternate)\n▪Virginia Caine            (NMA)\nConsultants\n▪Monica Farley            (VAMC/Emory)\n▪Keith Klugman          (BMGF)\n▪George Kuchel           (UConn)\n▪Kathy Poehling         (Wake Forest)\n▪Arthur Reingold        (UC Berkley)\n▪Lorry Rubin                 (CCMC)\n▪Richard Zimmerman (U. of Pittsburgh)Pneumococcal Vaccines Work Group\nDivision of Bacterial Diseases\n▪Adam Cohen\n▪Ryan Gierke             \n▪Noele Nelson    \nImmunization Safety Office\n▪Pedro Moro               \nImmunization Services Division\n▪Andrew Leidner\n▪Liz VelazquezArctic Investigations Program\n▪Marc Fischer\nCDC Lead\n▪Miwako Kobayashi\nGRADE/ EtR  consultants\n▪Doug Campos -Outcalt\n▪Rebecca MorganCDC Contributors and Consultants\n051015202530354045\n2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022Cases per 100,000 population\nYearAge <5 Age 19-49\nAge 50-64 Age ≥65In 2020 during the COVID -19 pandemic, IPD rates reached a historically \nlow level in all age groups\nPCV13: adultsPCV13: children\n4COVID -19\nAdapted from Gierke February 2024 ACIP meeting presentationIPD=invasive pneumococcal disease\nDuring 2021 –2023, new pneumococcal conjugate vaccines PCV15 \nand PCV20  were recommended for both adults and children\n2021 2023 2022\nPCV15 : ChildrenPCV20 : Expanded \nindication for adults \nwho previously \nreceived PCV13\nPCV20 : ChildrenPCV15 and PCV20 : \nAdults who have not \nreceived PCV or whose \nvaccination history is \nunknown\nPCV13=13 -valent pneumococcal conjugate vaccine\nPCV15=15 -valent pneumococcal conjugate vaccine\nPCV20=20 -valent pneumococcal conjugate vaccine\nAdult Pneumococcal Vaccines\n1 3 4 5 6\nA6\nB7 \nF9\nV1\n41\n8\nC1\n9\nA1\n9\nF2\n3\nF2\n2\nF3\n3\nF8 1\n0\nA1\n1\nA1\n2\nF1\n5\nB2 9\nN1\n7\nF2\n01\n5\nA1\n5\nC1\n6\nF2\n3\nA2\n3\nB2\n4\nF3\n13\n5\nB\nPCV15\nPCV20\nPPSV23\nPCV21\n1. U.S. FDA Approves CAPVAXIVE ™ (Pneumococcal 21 -valent Conjugate Vaccine) for Prevention of Invasive Pneumococcal Disease and Pneumococcal Pneumonia in Adults  - Merck.com21-valent pneumococcal conjugate vaccine (CAPVAXIVETM, Merck):\n•Approved by the FDA for adults aged ≥18 years on June 17, 20241\nPCV13=13 -valent pneumococcal conjugate vaccine\nPCV15=15 -valent pneumococcal conjugate vaccine\nPCV20=20 -valent pneumococcal conjugate vaccine\nPPSV23=23 -valent pneumococcal polysaccharide vaccine\nNew Adult Pneumococcal Vaccines in Advanced Stages of Development\n1 3 4 5 6\nA6\nB7 \nF9\nV1\n41\n8\nC1\n9\nA1\n9\nF2\n3\nF2\n2\nF3\n3\nF8 1\n0\nA1\n1\nA1\n2\nF1\n5\nB2 9\nN1\n7\nF2\n01\n5\nA1\n5\nC1\n6\nF2\n3\nA2\n3\nB2\n4\nF3\n13\n5\nB1\n6\nF7\nC\nPCV15\nPCV20\nPPSV23\nPCV21\nPn-\nMAPS24v\nVAX -24\nVAX -31\n1. Chichili  et al. Vaccine 2022; 2 .Vaxcyte  Completes Enrollment of Phase 2 Study Evaluating VAX -24 for the Prevention of Invasive Pneumococcal Disease (IPD) in Infants - Vaxcyte , Inc. ; 3. Vaxcyte  Doses First Participants in Phase 1/2 Clinical Study Evaluating VAX -31 for the \nPrevention of Invasive Pneumococcal Disease in Adults - Vaxcyte , Inc. ; Investor Overview (vaxcyte.com) , May 8 202424-valent pneumococcal vaccines:\n•Pn-MAPS24v (GSK): Completed phase 1/2 study for adults; Breakthrough  Therapy Designation \ngranted and Phase 3 study in preparation; undergoing phase 2 studies in infants1\n•VAX -24 (Vaxcyte ): Completed phase 1/2 studies for adults, completed enrollment for phase 2 studies \nin infants2\n31-valent pneumococcal vaccine (VAX -31, Vaxcyte ):\n•Completed enrollment of phase 1/2 study in adults aged ≥50 years3\n1345366\n0102030405060708090100Percent IPD\nPCV20/ non-PCV21 PCV20 and PCV21\nPCV21/ non-PCV20 NVT747388\n0102030405060708090100Percent IPD\nPCV20/ non-PCV21 PCV20 and PCV21\nPCV21/ non-PCV20 NVTProportion of IPD by vaccine -type among adults with a pneumococcal \nvaccine indication, 2018−2022\nPCV20/ non -PCV21 serotype:  1, 4, 5, 6B, 9V, 14, 18C, 19F, 23F, 15B\nPCV20/ in -PCV21 serotypes: 3, 6A, 7F, 19A, 22F, 33F, 8, 10A, 11A, 12F, +6C \nPCV21/ non -PCV20  serotypes: 9N, 17F ,20, 15A, 15C, 16F, 23A, 23B, 24F, 31, 35B PCV21:\n85%  coverage\n8PCV20:\n54%  coveragePCV21:\n81%  coverage\nPCV20:\n58%  coverage19-64 years old ( with a risk -based indication ) ≥65 years old\nGierke February 2024 ACIP meeting presentation \n▪Adults experiencing homelessness (especially Western United States)\n•100–300 times higher serotype 4  IPD incidence reported in people experiencing \nhomelessness (PEH) vs. non -PEH in the Western United States1\n▪Adults in Alaska (especially Alaska Native adults)\n•88-fold increase in serotype 4 IPD incidence reported in adults in Alaska, 2011 –2018 \nvs. 2019 –20202 Increase in serotype 4  (included in currently available vaccines, \nnot in PCV21) IPD reported in certain subpopulations\n1. Upsurge of Conjugate Vaccine Serotype 4 Invasive Pneumococcal Disease Clusters Among Adults Experiencing Homelessness in C alifornia, Colorado, and New Mexico | The \nJournal of Infectious Diseases | Oxford Academic (oup.com)\n2. Invasive Pneumococcal Disease and Potential Impact of Pneumococcal Conjugate Vaccines Among Adults, Including Persons Experie ncing Homelessness —Alaska, 2011 –2020 | \nClinical Infectious Diseases | Oxford Academic (oup.com)Kobayashi February 2024 ACIP meeting presentation \n▪The following groups are currently recommended to receive a dose of\npneumococcal conjugate vaccine (PCV):\n•Adults aged ≥65 years who have not received a PCV1\n•Adults aged 19 –64 years with certain underlying conditions or risk factors2 who\nhave not received a PCV1\n•Certain adults who have received PCV13 but have not received PCV203Current Pneumococcal Vaccine Recommendations for Adults \nand Vaccine Coverage \n1. Excludes PCV7\n2. alcoholism; chronic heart, liver, or lung disease; chronic renal failure; cigarette smoking; cochlear implant; congenital or acquired asplenia; CSF leak; diabetes mellitus; generalized malignancy; HIV infection; \nHodgkin disease; immunodeficiency; iatrogenic immunosuppression; leukemia, lymphoma, or multiple myeloma; nephrotic syndrome;  solid organ transplant; or sickle cell disease or other \nhemoglobinopathies\n3. Adults who have not completed the recommended vaccine series, or shared clinical decision -making for adults aged ≥65 years who h ave completed the recommended vaccine series\nPneumococcal Vaccine for Adults Aged ≥19 Years: Recommendations of the Advisory Committee on Immunization Practices, United S tates, 2023 | MMWR (cdc.gov)\n▪Coverage of ≥1 dose of any pneumococcal vaccine\n•Adults aged 19 –64 years with risk -based indication: 22.2%\n•Adults aged ≥65 years: 65.8%Adults with risk -based vaccine recommendations have lower \nvaccine coverage compared with those with age -based \nrecommendations\nVaccination Coverage among Adults in the United States, National Health Interview Survey, 2021 | CDC\n1. Should PCV21  be recommended for U.S. adults aged ≥19 years who \ncurrently have a recommendation to receive a PCV*?\n*Includes:\n• Adults aged ≥65 years who have never received a PCV\n• Adults aged 19 –64 years with a risk condition, who have never received a PCV\n• Adults aged ≥19 year who have received a PCV (i.e ., PCV7  or PCV13), but have not completed the recommended series\n• PCV20 use based on shared clinical decision -making for adults ≥65 years who have completed the recommended series with PCV13 and  PPSV23\n2. Should PCV21  be recommended for U.S. adults aged 50 –64 years who \ncurrently do not have a risk -based pneumococcal vaccine indication?\n3. Should PCV21  be recommended for U.S. adults aged 19 –49 years who \ncurrently do not have a risk -based pneumococcal vaccine indication?\n•Questions 2 and 3 would result in a new age -based recommendation for these groups.Policy Questions Being Considered by the Work Group \nACIP recommends PCV21 as an option for adults aged ≥19 years \nwho currently have a recommendation to receive a dose of PCV. Proposed Voting Language\n13\nIntroduction Dr. Jamie Loehr (ACIP , WG Chair)\nEconomic analysis and public health impact of \nPCV21 use in adultsDr. Charles Stoecker (Tulane)\nComparison of economic analysis of PCV21 use in \nadultsDr. Andrew Leidner (CDC/NCIRD)\nSummary of WG interpretation of EtR and policy \noptions on PCV21 use in adultsDr. Miwako Kobayashi (CDC/NCIRD)\nClinical considerations for PCV21 use in adults Dr. Miwako Kobayashi (CDC/NCIRD)Today’s Session", "summary": "Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. Pneumococcal Vaccines June 2024, ACIP Meeting June 27, 2024 Pneumococcal Vaccine Work Group Chair James Loehr, MD, FAAFP ACIP Members ▪Jamie Loehr  (Chair) ▪Sarah Long…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/01-Pneumococcal-Loehr-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 14}
{"title": "02 Pneumococcal Stoecker 508", "content": "1Economic Assessment of PCV21 in U.S. Adults\nCharles Stoecker\nTulane University\nSchool of Public Health and Tropical Medicine\nACIP\nJune 27, 2024\n\n2Conflicts of Interest\n❑Dr. Stoecker has no conflicts of interest to declare.\n3Acronyms\n❑ PCV: pneumococcal conjugate vaccine\n❑ PCV20: 20 valent PCV\n❑ PCV21: 21 valent PCV\n❑ VE: vaccine effectiveness\n❑ VT: vaccine type\n❑ ST: serotype\n❑ NBP: non -bacteremic  pneumonia\n❑ IPD: invasive pneumococcal disease\n❑ IPT: inpatient\n❑ OPT: outpatient\n❑ QALY: quality adjusted life year\n❑ IC: immunocompromised\n❑ CMC: chronic medical conditions, but not IC\n❑ NIS: National Immunization Survey\n❑ ABCs: Active Bacterial Core Surveillance System\n4Methods:  Study Question\n❑Evaluate cost effectiveness of using PCV21 in adults\n❑Evaluate\n▪Program cost/savings\n▪Changes in disease, medical costs, nonmedical costs, and work \nproductivity costs\n•Limited societal perspective\n▪Population\n•Separate cohorts of 4,256,608 19 -year -olds, 3,990,700 42 -year -olds, \n4,051,078 50 -year -olds, or 3,567,978 65 -year -olds for specific questions\n•Separate model buckets for:\noImmunocompromised (IC) – HIV, Cancer, Organ Transplants, \nDialysis\noChronic medical conditions (CMC) – Diabetes, Heart Disease, Lung \nDisease, Liver Disease, Alcoholism\noOthers –”General”\n5Methods:  Interventions\n❑Five strategies to evaluate\nIntervention Comparator\nQuestion 1a Age -based vaccination at 65 with PCV21 Age -based vaccination at 65 with PCV20\nQuestion 1b Risk -based vaccination with PCV21 Risk -based vaccination with PCV20\nQuestion 2 Age -based vaccination at 50 with PCV21 Age -based vaccination at 65 with PCV21\nQuestion 3 Age -based vaccination at 19 with PCV21 Age -based vaccination at 50 with PCV21\nSupplemental PCV21 Dose after PCV20\nVaccination at 65 with PCV20 and 66 with PCV21 \n(all) Age -based vaccination at 65 with PCV20\nVaccination at 65 with PCV20 and 70 with PCV21 \n(all) Age -based vaccination at 65 with PCV20\nRisk -based vaccination with PCV20 and \nvaccination after 1 year with PCV21 (CMC/IC) Risk -based vaccination with PCV20\nRisk -based vaccination with PCV20 and \nvaccination after 5 years with PCV21 (CMC/IC) Risk -based vaccination with PCV20\n6Methods:  Economic Model\n❑Cohort Model\n▪Cost per quality adjusted life year (QALY) gained\n▪Cost per life year gained\n❑Compare each intervention to comparator strategy and \ncalculate incremental cost effectiveness ratio\n▪Divide change in costs by change in QALYs\n❑Costs in 2023$\n▪Inflated by the Medical Care component of Consumer Price Index\n❑Future costs and outcomes discounted by 3% annually\n7Methods:  Health Outcomes\n❑\n❑\n❑\n❑\n❑\n❑\n❑Cases of Invasive Pneumococcal Disease (IPD)\nCases of Hospitalized (IPT) Nonbacteremic Pneumonia \n(NBP)\nCases of outpatient (OPT) NBP\nDeaths due to IPD\nDeaths due to IPT NBP\nQAL Ys\nLife Y ears\n8Conceptual Model\nNBP\nBackground mortality from non-pneumococcus related illness is included in all branches, but not displayed in the model for brevity.IPT Case\nIPT Case\nOPT Case\n9Model Inputs\n❑\n❑\n❑IPD rates, all -cause IPT and OPT NBP rates, IPD cases resulting in \nfatality were estimated by age - and risk group (general/CMC/IC). \nAge -group specific IPT NBP case fatality rates were applied to all \nrisk groups\nVaccine effectiveness (VE) was estimated by risk group and \noutcome (IPD/NBP).\n▪\n▪VE against serotype 3 was lower than other VT\nVE was the same across PCV20 and PCV21\n❑\n❑Vaccine coverage was estimated by age group (19 –49, 50 –64, 65+) \nand scenario (risk based, supplemental)\nHerd inputs updated from previous iteration\n▪\n▪\n▪New baseline estimation strategy\nBigger initial effect\nPlateau after 6 years\nSee supplemental slides for the specific estimates used in the model. \n10Serotype Group18-49\nYears50-64\nYears65-74\nYears75-84\nYears85+\nYears\n% PCV20 only -4-19F\n   (1, 5, 6B, 9V, 14, 18C, 23F, 15B, including \nisolates reported as 15BC)1.99% 1.52% 3.09% 1.01% 1.08%\n% PCV20 & PCV21 -3\n(6A, 7F, 19A, 22F, 33F, 8, 10A, 11A, 12F) +6C 34.44% 41.95% 32.72% 32.32% 33.33%\n% PCV21 only -35B\n   (9N, 17F, 20, 15A, 15C, 16F, 23A, 23B, 24F, 31)30.13% 30.70% 31.48% 29.29% 35.48%\n% serotype 3 13.91% 12.46% 17.28% 21.21% 14.25%\n% serotype 4 4.97% 2.43% 1.23% 0.00% 0.00%\n% serotype 19F 4.97% 4.56% 3.70% 3.03% 3.01%\n% serotype 35B 2.65% 0.91% 4.32% 5.05% 3.23%\nRatio PCV21 only:PCV20 only serotypes 2.75 3.71 4.46 8.50 9.46\nSource: Active Bacterial Core Surveillance 2018 -2019. For multivariate sensitivity analyses distributions are beta -pert with -/+20% for low and high.IPD Serotype Distributions, General\n11Serotype Group18-49\nYears50-64\nYears65-74\nYears75-84\nYears85+\nYears\n% PCV20 only -4-19F\n   (1, 5, 6B, 9V, 14, 18C, 23F, 15B, including \nisolates reported as 15BC)0.49% 0.71% 1.88% 2.17% 1.81%\n% PCV20 & PCV21 -3\n(6A, 7F, 19A, 22F, 33F, 8, 10A, 11A, 12F) +6C 36.99% 33.62% 30.36% 32.79% 28.62%\n% PCV21 only -35B\n   (9N, 17F, 20, 15A, 15C, 16F, 23A, 23B, 24F, 31)30.33% 32.67% 30.83% 32.52% 33.70%\n% serotype 3 11.34% 17.96% 21.91% 17.07% 17.39%\n% serotype 4 9.99% 4.35% 1.25% 0.27% 0.72%\n% serotype 19F 3.08% 2.45% 2.66% 2.44% 2.17%\n% serotype 35B 2.59% 3.01% 4.23% 5.15% 6.88%\nRatio PCV21 only:PCV20 only serotypes 2.43 4.75 6.06 7.72 8.63IPD Serotype Distributions, CMC\nSource: Active Bacterial Core Surveillance 2018 -2019. For multivariate sensitivity analyses distributions are beta -pert with -/+20% for low and high.\n12IPD Serotype Distributions, IC\nSerotype Group18-49\nYears50-64\nYears65-74\nYears75-84\nYears85+\nYears\n% PCV20 only -4-19F\n   (1, 5, 6B, 9V, 14, 18C, 23F, 15B, including \nisolates reported as 15BC)6.02% 3.92% 3.30% 2.88% 0.00%\n% PCV20 & PCV21 -3\n(6A, 7F, 19A, 22F, 33F, 8, 10A, 11A, 12F) +6C 28.92% 31.63% 30.03% 37.50% 48.31%\n% PCV21 only -35B\n   (9N, 17F, 20, 15A, 15C, 16F, 23A, 23B, 24F, 31)31.33% 33.73% 33.99% 26.44% 25.84%\n% serotype 3 15.66% 8.43% 11.55% 10.10% 4.49%\n% serotype 4 1.20% 1.20% 1.32% 0.00% 0.00%\n% serotype 19F 3.61% 3.61% 3.30% 1.44% 5.62%\n% serotype 35B 6.02% 6.63% 8.91% 9.62% 5.62%\nRatio PCV21 only:PCV20 only serotypes 3.45 4.62 5.42 8.35 5.60\nSource: Active Bacterial Core Surveillance 2018 -2019. For multivariate sensitivity analyses distributions are beta -pert with -/+20% for low and high.\n13NBP Serotype Distributions\nSerotype Group18-49\nYears50-64\nYears65+\nYears\n% PCV20 only -4-19F\n   (1, 5, 6B, 9V, 14, 18C, 23F, 15B)0.6% 0.7% 1.1%\n% PCV20 & PCV21 -3\n(6A, 7F, 19A, 22F, 33F, 8, 10A, 11A, 12F) +6C 3.0% 4.5% 3.9%\n% PCV21 only -35B\n   (9N, 17F, 20, 15A, 15C, 16F, 23A, 23B, 24F, 31)3.2% 4.2% 2.4%\n% serotype 3 1.1% 2.0% 1.4%\n% serotype 4 0.0% 0.2% 0.2%\n% serotype 19F 0.1% 0.9% 0.7%\n% serotype 35B 0.8% 0.6% 0.7%\nRatio PCV21 only:PCV20 only serotypes 5.7 2.7 1.6\nSource: Merck adjusted SSUAD serotype distribution data. \nNote that the serotype distribution is among all community -acquired pneumonia, not limited to pneumococcal pneumonia.\n For multivariate sensitivity analyses distributions are beta -pert with -/+20% for low and high.\n14Waning Immunity Assumptions\n❑\n❑No decline in effectiveness for first five years a\nWane to zero over next 10 years b\naPatterson  S, Webber C, Patton M, Drews  W, Huijts  SM, Bolkenbaas  M, et al. A post hoc assessment of duration of protection in CAPiTA  (Community \nAcquired Pneumonia immunization Trial in Adults). Trials in Vaccinology. 2016;5.:92 -96.\nb van Werkhoven  CH, Huijts  SM, Bolkenbaas  M, Grobbee  DE, Bonten  MJ. The Impact of Age on the Efficacy of 13 -valent Pneumococcal Conjugate \nVaccine in Elderly. Clin Infect Dis 2015;61(12):1835 -8.00.20.40.60.81\n0 5 10 15 20% Initial Effectiveness\nYears Since Vaccination\n15Vaccine Price\n❑\n❑\n▪\n❑\n❑\n❑PCV20 $288.66a\nPCV21 $319.43b\nSensitivity analysis with PCV21 price 5% higher ($335.60)\nAdministration 19 -64 years: $30.49c\nAdministration 65+ years:  $21.07d\nTravel + patient time cost: $44.46e\na Payment Allowance Limits for Medicare Part B for PCV20.\nb Applied ratio of PCV21 to PCV20 price from manufacturer model and applied to PCV20 Medicare price. Sensitivity analysis uses upper bound of manufacturer \nPCV21 price range.\nc Tsai et al. AJPM 2019. Updated to 2023 dollars.\nd Average Medicare maximum allowable reimbursement for immunization administration (HCPCS code 90471) across all Medicare Admin istrative Contractors, \n2023.\ne Travel cost from Maciosek  et al. Am J Prev Med 2006. Updated to 2023 dollars.\n16Sensitivity Analyses\n❑\n▪\n❑\n❑\n▪\n❑\n▪\n▪\n❑Higher PCV21 Price \n5% higher: $335.60 vs $319.43\nNo PCV20 type indirect protections for adults from \nchildhood program\nSerotype 4 disease at 30% of pneumococcal disease\nDecrease other serotypes proportionally to preserve overall \ndisease rates\nFix disease QAL Y decrements by age \nOnly for moving age -based recommendation to 19 or 50 years\nSet QALY decrements to age 19 decrements for all ages\nAlternate QAL Y decrements\n17PCV21 Overview\nQuestion 1a\nPCV1 @Age 65Question 1b\nPCV21 @CMC/ICQuestion 2 \nPCV21 @Age 50Question 3\nPCV21 @Age 19\nHealth Outcomes\nIPD Cases -889 ( -1099, -624) -194 ( -233, -139) 215 ( -101,534) 223 (112,339)\nHospitalized Pneumonia Cases -1630 ( -2210, -929) -368 ( -489, -207) 1050 (423,1751) 350 (159,544)\nNon -hospitalized Pneumonia \nCases -3663 ( -5050, -2082) -1427 ( -1927, -801) 247 ( -1732,2421) 926 (77,1911)\nDeaths due to IPD -108 ( -137, -74) -23 (-28,-16) 36 (-3,75) 28 (16,42)\nDeaths due to Pneumonia -60 (-90,-31) -11 (-16,-6) 48 (14,86) 11 (4,20)\nQALYs 1302 (926,1613) 363 (265,435) 52 (-633,744) -507 ( -759, -261)\nLife-years 2082 (1476,2591) 513 (376,614) -389 ( -1331,564) -682 ( -1010, -360)\nCosts (million $)\nTotal Cost 5 (-12,30) -29 (-38,-17) -5 (-119,121) 185 (111,254)\nMedical Costs -60 (-74,-42) -26 (-31,-18) -34 (-74,9) 35 (18,51)\nVaccine Costs 90 (79,101) 12 (12,13) 75 (-108,258) 129 (40,219)\nWork Loss -24 (-30,-17) -16 (-20,-11) -47 (-78,-16) 21 (9,33)\nCost Ratios ($)\nCost/QALY4,132 (C -S, 18,599) C-S (C-S, C-S)C-S (187,994*, \n162,634) D (D, D)\nCost/Life -year2584 (C -S, 11,579) C-S (C-S,  C -S)13,675* (89,406*, \n214,539) D(D, D)\n95% CI in parenthesis; * Indicates dollars saved per QALY or Life -year lost; C -S indicates cost -saving; D indicates dominated.\n18Question 1a: Vaccination at age 65 with PCV21\nBasePCV21 @ \n$335.60PCV20 Child \nIndirect 0%Serotype 4 @ \n30%Tang QALY \nValues\nHealth Outcomes\nIPD Cases -889 -889 -855 152 -889\nHospitalized Pneumonia Cases -1,630 -1,630 -1,019 -422 -1,630\nNon -hospitalized Pneumonia Cases -3,663 -3,663 -2,320 -807 -3,663\nDeaths due to IPD -108 -108 -104 18 -108\nDeaths due to Pneumonia -60 -60 -37 -16 -60\nQALYs 1,302 1,302 1,098 -45 1,321\nLife-years 2,082 2,082 1,771 -74 2,082\nCosts (million $)\nTotal Cost $5 $37 $24 $85 $5\nMedical Costs -$60 -$60 -$46 -$5 -$60\nVaccine Costs $90 $121 $90 $90 $90\nWork Loss -$24 -$24 -$20 $1 -$24\nCost Ratios ($)\nCost/QALY 4,132 28,061 21,947 Dominated 4,073\nCost/Life -year 2,584 17,549 13,602 Dominated 2,584Cohort of 65 -year -olds.  Comparator is PCV20 at age 65.\n19Question 1b: Vaccination at CMC/IC with PCV21\nBasePCV21 @ \n$335.60PCV20 Child \nIndirect 0%Serotype 4 @ \n30%Tang QALY \nValues\nHealth Outcomes\nIPD Cases-194 -194 -188 29 -194\nHospitalized Pneumonia Cases-368 -368 -265 -190 -368\nNon -hospitalized Pneumonia Cases\n-1,427 -1,427 -1,128 -694 -1,427\nDeaths due to IPD-23 -23 -22 3 -23\nDeaths due to Pneumonia-11 -11 -8 -6 -11\nQALYs363 363 324 29 361\nLife-years513 513 458 32 513\nCosts (million $)\nTotal Cost-$29 -$22 -$24 $3 -$29\nMedical Costs-$26 -$26 -$22 -$7 -$26\nVaccine Costs$12 $19 $12 $12 $12\nWork Loss-$16 -$16 -$14 -$3 -$16\nCost Ratios ($)\nCost/QALYCost -Saving Cost -Saving Cost -Saving 111,812 Cost -Saving\nCost/Life -year Cost -Saving Cost -Saving Cost -Saving 98,126 Cost -SavingCohort of 42 -year -olds.  Comparator is PCV20 at CMC/IC.\n20Question 1b: Vaccination at CMC/IC with PCV21\nCohort of 42 -year -olds.  Comparator is PCV20 at CMC/IC.\nSerotype 4 @ \n5%Serotype 4 @ \n10%Serotype 4 @ \n15%Serotype 4 @ \n20%Serotype 4 @ \n25%Serotype 4 @ \n30%Serotype 4 @ \n35%\nHealth Outcomes\nIPD Cases -184 -141 -99 -56 -13 29 72\nHospitalized Pneumonia Cases -345 -314 -283 -252 -221 -190 -159\nNon -hospitalized Pneumonia \nCases-1,327 -1,201 -1,074 -947 -821 -694 -567\nDeaths due to IPD -21 -16 -11 -6 -2 3 8\nDeaths due to Pneumonia -11 -10 -9 -8 -7 -6 -5\nQALYs 345 282 218 155 92 29 -35\nLife-years 486 395 304 214 123 32 -58\nCosts (million $)\nTotal Cost -27 -21 -15 -9 -3 3 9\nMedical Costs -24 -21 -17 -14 -10 -7 -3\nVaccine Costs 12 12 12 12 12 12 12\nWork Loss -15 -13 -10 -8 -5 -3 0\nCost Ratios ($)\nCost/QALY Cost -Saving Cost -Saving Cost -Saving Cost -Saving Cost -Saving 111,812 Dominated\nCost/Life -year Cost -Saving Cost -Saving Cost -Saving Cost -Saving Cost -Saving 98,126 Dominated\nBase case serotype 4 distributions are age, risk, and disease condition specific as displayed earlier in the slides.  They ra nge  from 0 to 9.99%\n21Question 2: Vaccination at age 50\nBasePCV21 @ \n$335.60PCV20 Child \nIndirect 0%Serotype 4 @ \n30%Fix QALY \nDecrementsTang QALY \nDecrements\nHealth Outcomes\nIPD Cases215 215 398 131 215 215\nHospitalized Pneumonia Cases1,050 1,050 2,220 775 1,050 1,050\nNon -hospitalized Pneumonia \nCases247 247 2,175 282 247 247\nDeaths due to IPD36 36 62 23 36 36\nDeaths due to Pneumonia48 48 93 35 48 48\nQALYs52 52 -283 45 -3 17\nLife-years-389 -389 -1,061 -257 -389 -389\nCosts (million $)\nTotal Cost-$5 -$3 -$4 $19 -$5 -$5\nMedical Costs-$34 -$34 -$25 -$23 -$34 -$34\nVaccine Costs$75 $78 $75 $75 $75 $75\nWork Loss-$47 -$47 -$54 -$33 -$47 -$47\nCost Ratios ($)\nCost/QALYCost -Saving Cost -Saving 15,489* 429,479 1,739,015* Cost -Saving\nCost/Life -year 13,675* 6,916* 4,138* Dominated 13,675* 13,675*Cohort of 50 -year -olds.  Comparator is PCV21 at CMC/IC or age 65.\n* Dollars saved per QALY or Life -year lost.\n22Question 2 Modeling Strategies\n❑“Moving age -based recommendation from 65 to 50”\n▪Shifts disease burden from younger to older adults\n▪Save the cost of vaccinating 65 -year -olds\n❑“Adding vaccination at 50 in addition to 65”\n▪Isolates disease burden reduction from 50– to 64 -year -olds\n•Convenient since we assume 15 -year vaccine duration\n▪Clinicians may be unwilling to not re -vaccinate at age 65 in above \nrecommendation\n23Question 2: Vaccination at age 50 and 65\nBasePCV21 @ \n$335.60PCV20 Child \nIndirect 0%Serotype 4 @ \n30%Fix QALY \nDecrementsTang QALY \nDecrements\nHealth Outcomes\nIPD Cases -424 -424 -560 -307 -424 -424\nHospitalized Pneumonia Cases -462 -462 -412 -306 -462 -462\nNon -hospitalized Pneumonia \nCases-3,202 -3,202 -3,835 -2,184 -3,202 -3,202\nDeaths due to IPD -41 -41 -53 -30 -41 -41\nDeaths due to Pneumonia -8 -8 -3 -5 -8 -8\nQALYs 1,105 1,105 1,408 780 1,096 1,074\nLife-years 1,262 1,262 1,574 895 1,262 1,262\nCosts (million $)\nTotal Cost $298 $317 $253 $344 298 $298\nMedical Costs -$84 -$84 -$110 -$59 -84 -$84\nVaccine Costs $450 $468 $450 $450 450 $450\nWork Loss -$67 -$67 -$87 -$47 -67 -$67\nCost Ratios ($)\nCost/QALY 269,932 286,553 179,685 440,518 272,038 277,778\nCost/Life -year 236,322 250,873 160,744 384,319 236,322 236,322Cohort of 50 -year -olds.  Comparator is PCV21 at CMC/IC or age 65.\n24Question 3: Vaccination at age 19\nBasePCV21 @ \n$335.60PCV20 Child \nIndirect 0%Serotype 4 @ \n30%Fix QALY \nDecrementsTang QALY \nDecrements\nHealth Outcomes\nIPD Cases223 223 373 158 223 223\nHospitalized Pneumonia Cases350 350 564 244 350 350\nNon -hospitalized Pneumonia \nCases926 926 1,649 659 926 926\nDeaths due to IPD28 28 46 20 28 28\nDeaths due to Pneumonia11 11 17 8 11 11\nQALYs-507 -507 -835 -358 -509 -498\nLife-years-682 -682 -1,113 -481 -682 -682\nCosts (million $)\nTotal Cost$185 $190 $222 $168 $185 $185\nMedical Costs$35 $35 $57 $25 $35 $35\nVaccine Costs$129 $134 $129 $129 $129 $129\nWork Loss$21 $21 $35 $15 $21 $21\nCost Ratios ($)\nCost/QALYDominated Dominated Dominated Dominated Dominated Dominated\nCost/Life -year Dominated Dominated Dominated Dominated Dominated DominatedCohort of 19 -year -olds.  Comparator is PCV21 at CMC/IC or age 50.\n25Supplemental PCV21 One Year after PCV20 (all)\nBasePCV21 @ \n$335.60PCV20 Child \nIndirect 0%Serotype 4 @ \n30%Tang QALY \nDecrements\nHealth Outcomes\nIPD Cases-847 -847 -866 -525 -847\nHospitalized Pneumonia Cases-1,875 -1,875 -1,973 -1,276 -1,875\nNon -hospitalized Pneumonia Cases\n-3,981 -3,981 -4,065 -2,690 -3,981\nDeaths due to IPD-104 -104 -107 -65 -104\nDeaths due to Pneumonia-70 -70 -74 -48 -70\nQALYs1,261 1,261 1,285 808 1,286\nLife-years2,059 2,059 2,110 1,325 2,059\nCosts (million $)\nTotal Cost$557 $584 $555 $587 $557\nMedical Costs-$65 -$65 -$67 -$43 -$65\nVaccine Costs$644 $671 $644 $644 $644\nWork Loss-$23 -$23 -$23 -$15 -$23\nCost Ratios ($)\nCost/QALY442,010 463,475 431,656 726,607 433,172\nCost/Life -year 270,614 283,756 262,879 443,207 270,614Cohort of 66 -year -olds.  Comparator is no additional vaccine.\n26Supplemental PCV21 Five Years after PCV20 (all)\nBasePCV21 @ \n$335.60PCV20 Child \nIndirect 0%Serotype 4 @ \n30%Tang QALY \nDecrements\nHealth Outcomes\nIPD Cases-1,035 -1,035 -1,300 -673 -1,035\nHospitalized Pneumonia Cases-3,360 -3,360 -4,852 -2,355 -3,360\nNon -hospitalized Pneumonia Cases\n-5,770 -5,770 -8,028 -4,015 -5,770\nDeaths due to IPD-129 -129 -163 -84 -129\nDeaths due to Pneumonia-132 -132 -193 -93 -132\nQALYs1,580 1,580 2,099 1,064 1,600\nLife-years2,608 2,608 3,460 1,757 2,608\nCosts (million $)\nTotal Cost$485 $510 $439 $524 $485\nMedical Costs-$102 -$102 -$142 -$70 -$102\nVaccine Costs$608 $634 $608 $608 $608\nWork Loss-$22 -$22 -$28 -$15 -$22\nCost Ratios ($)\nCost/QALY306,901 323,076 209,103 492,194 302,891\nCost/Life -year 185,860 195,656 126,871 298,071 185,860Cohort of 70 -year -olds.  Comparator is no additional vaccine.\n27Supplemental PCV21 1/5 years after PCV20 Among Adults with CMC/IC\nComparator is no additional vaccine.\n1 Year\nCohort @411 Year\nCohort @451 Year\nCohort @555 Years\nCohort @415 Years\nCohort @455 Years\nCohort @55\nHealth Outcomes\nIPD Cases-508 -532 -514 -553 -580 -584\nHospitalized Pneumonia Cases-933 -990 -1,056 -1,049 -1,119 -1,239\nNon -hospitalized Pneumonia \nCases-3,593 -3,504 -3,031 -3,903 -3,823 -3,448\nDeaths due to IPD-57 -62 -63 -63 -68 -73\nDeaths due to Pneumonia-29 -32 -37 -34 -37 -44\nQALYs936 981 897 1,004 1,053 1,010\nLife-years1,320 1,394 1,332 1,424 1,506 1,504\nCosts (million $)\nTotal Cost$314 $291 $199 $314 $287 $208\nMedical Costs-$66 -$68 -$61 -$71 -$73 -$69\nVaccine Costs$421 $399 $289 $428 $402 $309\nWork Loss-$41 -$40 -$28 -$44 -$42 -$31\nCost Ratios ($)\nCost/QALY335,330 296,483 221,736 312,933 272,520 206,191\nCost/Life -year 237,779 208,572 149,339 220,664 190,605 138,491\n28Alternate Efficiency Measures\n(Does not account for overlap between measures)\nNumber needed to vaccinate to prevent…\nPCV21 \n@65PCV21 \n@CMC/ICPCV21 \n@50 & @65PCV21 Suppl \n@66PCV21 Suppl \n@70\nHospitalization 643 572 7,127 512 300\nCase 263 180 974 209 130\nDeath 9,758 9,026 155,708 8,087 5,109\nPCV21 \n@65PCV21 \n@CMC/ICPCV21 \n@50 & @65PCV21 Suppl \n@66PCV21 Suppl \n@70\nHospitalization $2,227 Cost -Saving $335,952 $205,491 $111,219 \nCase $906 Cost -Saving $72,898 $83,279 $47,910 \nDeath $33,521 Cost -Saving $6,139,249 $3,220,043 $1,879,564 $ per averted…\n29Limitations\n❑Sequelae from IPD not modeled explicitly\n❑Ranges on serotype distributions and other IPD data from ABCs \nare +/ - 25% by assumption\n❑Uncertainties about the pneumococcal disease trends due to \npneumococcal serotypes that are no longer included in PCV21 \n(e.g., serotype 4, 19F)\n❑Uncertainties about the indirect effects from pediatric PCV20 use\n❑Disruption from changing pneumococcal schedule not modeled\n❑Disease rates are constant within specified age bins as single -year \nof age disease estimates are unlikely to be precise.\n30Summary\n❑ Replacing PCV20 with PCV21 at age 65 increases QAL Ys with modest increases in \ncost\n▪Simulations range from $4,000 to $28,000 / QALY in several scenarios\n▪Replacing PCV20 with PCV21 is dominated (lower QALYs and more costs) in a scenario where \nserotype 4 disease accounts for 30% of pneumococcal disease\n❑ Replacing PCV20 with PCV21 at diagnosis of IC or CMC before age 65 is cost -saving\n▪Cost is $110,000/QALY in a scenario where serotype 4 disease accounts for 30%\n▪At serotype 4 disease rates at 35% or above it results in decreased QALYs\n❑ Moving PCV21 vaccination from age 65 to age 50 increases case counts and deaths, \nbut also results in gains in QAL Ys\n▪Disease burden is shifted from younger adults to older adults who have lower background \nQALY values\n❑ Vaccinating at both age 50 and age 65 costs $300,000/QAL Y\n▪ Sensitivity analyses range from $200,000/QALY to $400,000/QALY\n❑ Vaccinating with PCV21 at age 19 instead of age 50 is dominated\n▪ Less health (both lower QALYs and more cases) and increased costs\n❑ Supplemental PCV21 at age 65 that includes all adults that previously had PCV20 \n(at age 65 or at CMC/IC) costs $400,000/QAL Y\n▪ If the supplemental dose  is delayed until age 70 the cost drops to $300,000/QALY\n❑ Supplemental PCV21 for the CMC/IC population ranges from $200,000 to $300,000 \nper QAL Y in the base case\n▪ Cost per QALY is 5 -30% lower if PCV21 is delayed 5 years after PCV20 vaccination rather than 1 year afterward\n▪ Assuming no herd immunity from childhood PCV20 program is associated with the lowest cost per QALYs\n31Thank you!\nPlease send comments to:\ncfstoecker@tulane.edu\nContributors:\nAndrew Leidner\nMiwako Kobayashi\nBo-Hyun Cho\nYin Wang\nCheryl Ward\nNational Center for Immunization & Respiratory Diseases\nHSREB – Econ Team\n\n32IPD Rates per 100k\nSource: Active Bacterial Core Surveillance System, 2017 -2018; NHIS 2017 –2018. For multivariate sensitivity analyses distributio ns are beta -pert with -/+20% for \nlow and high. Risk Group19-49\nYears50-64\nYears65-74\nYears75-84\nYears85+\nYears\nGeneral 2.09 6.09 8.25 13.90 33.06\nCMC 8.09 24.04 25.89 33.34 58.57\nIC 16.22 37.28 35.10 36.81 46.38\n33NBP Hospitalization Rates per 100k\nSource: MarketScan  & Optum databases. 2013 -2015 data. (Pelton et al. CID 2019) (95% CIs in parenthesis)Risk \nGroup19-49\nYears50-64\nYears65-74\nYears75+\nYears\nGeneral 35 (35, 36) 88 (87, 90) 191 (185, 197) 957 (938, 975)\nCMC 207 (202, 212) 429 (423, 425) 941 (925, 957) 2745 (2717, 2774)\nIC 701 (681, 721) 1226 (1207, 1244) 2124 (2087, 2162) 3992 (3944, 4040)\n34NBP Outpatient  Rates per 100k\nSource: Tong et al. 2014 data. BMC Health Serv Res 2018. For multivariate sensitivity analyses distributions are beta -pert with -/+20% f or low and high.Risk Group19-49\nYears50-64\nYears65-74\nYears75-84\nYears85+\nYears\nGeneral 322.92 385.04 491.98 1366.22 2378.97\nCMC 1872.91 1886.72 2410.70 3962.03 6899.00\nIC 6361.40 5352.10 5461.00 5738.10 9991.70\n35IPD Cases Resulting in Fatality\nSource: Active Bacterial Core Surveillance System, 2017 -2018. For multivariate sensitivity analyses distributions are beta -pert with -/+20% for low and high.Risk Group19-49\nYears50-64\nYears65-74\nYears75-84\nYears85+\nYears\nGeneral 5.54% 8.73% 7.93% 11.25% 17.30%\nCMC 7.24% 11.06% 12.22% 12.82% 22.97%\nIC 10.04% 14.27% 13.97% 11.33% 17.62%\n36IPT NBP Cases Resulting in Fatality\nBase Low High\n18-49 Years 1.6 0.4 2.9\n50-64 Years 2.8 1.1 4.4\n65-74 Years 3.5 1.5 5.5\n75-84 Years 4.1 2.2 6.0\n85+ Years 5.3 3.3 7.2\nSource: NIS2018 (lower bound: ICD -10 code J13 or J181 for primary diagnosis; upper bound: ICD -10 code J13 or J181 in ANY locatio n; base: mean of LB and UB). \nLow and High parameters used in beta -pert distribution \n37Vaccine Effectiveness\na. Bonten  NEJM 2015 (per protocol)\nb. Point estimate from Pilishvili et al. ISPPD2018 abstract, lower bound set to 0, upper bound from Lewis 2020 ISPPD poster\nc. Suaya  Vaccine 2018; 1477 -1483. \nd. Applied the ratio of IPD VE/Pneumonia VE for all PCV13 types to the point estimate for ST3 IPD VE.  General CMC IC\nPCV vs VT ( -ST3) IPDa 75.0 (41.4, 90.8) 75.0 (41.4, 90.8) 25.0 (13.8, 30.3)\nPCV vs ST3 IPDb 26.0 (0, 53.4) 26.0 (0, 53.4) 8.7 (0, 17.8)\nPCV vs VT ( -ST3) NBPc 66.7 (11.8, 89.3) 40.3 (11.4, 60.2) 15.0 (4.7, 21.8)\nPCV vs ST3 NBPd 15.6 (0, 32.0) 15.6 (0, 32.0) 5.2 (0, 10.7)\n38Coverage Rates\nBase Lowe Highe\nPCV Age -based 19 -49a 22.2 17.76 26.64\nPCV Age -based 50 -64b 39.65 23.3 56\nPCV, Age -based 65+c 56 49 63\nRisk -based (at development of CMC/IC)a 22.2 21 23.5\nPCV21 supplemental dosed 40.7 11.2 63.4\na. NHIS 2021 data https://www.cdc.gov/vaccines/imz -managers/coverage/adultvaxview/pubs -resources/vaccination -coverage -adults -2021.html ; Low and\nhigh in age -based 19 -49 context are -/+20% of base case; low and high in risk -based context are bounds of the 95% CI for coverag e among individuals\neligible for risk -based vaccination\nb. Low: NHIS 2021 for Zoster Vaccine in adults 60 -64 years; high: base estimate for PCV15/PCV20 coverage in adults 65 years and old er; base: mean\nc. High: NHIS 2021 any pneumococcal coverage; low: any PCV13 coverage data in Medicare beneficiaries aged ≥65 years, 2019; base:  mean\nd. % of PCV20 recipients who received PCV13 among Medicare Parts A/B beneficiaries as of Jan 17, 2024; low: coverage at age 66 y ears; high: coverage at\nage 80 -84 years\ne. Parameters for beta -pert distribution\n39Herd Effects from PCV20 in Children\n❑Apply serotype group -specific declines observed in \nPCV13 types (+6C, -3, -19F) in adults after PCV13 \nintroduction in children\n❑Apply to additional types in PCV20\n❑Run versions of the model with and without these herd \neffects to assess importance\nYear Base Lower Upper\n1 0.755161 0.707483 0.813869\n2 0.496227 0.459737 0.53535\n3 0.339094 0.312705 0.372755\n4 0.244074 0.220786 0.268572\n5 0.187125 0.166702 0.206661\n6 0.156599 0.138492 0.177142\n7+ No further declinesRemaining Share of Disease\nSource: Unpublished CDC model.\n40Utility Decrements\nVariable QAL Y DecrementsaImplied Healthy Days \nLostb\nIPD0.0709 \n(0.0509, 0.0909)25.9\nIPT NBP0.0709 \n(0.0509, 0.0909)25.9\nOPT NBP0.0045 \n(0.00399, 0.00501)1.6\na QALY values from Mangen  et al. 2015 Eur Respir J (95% CIs in parenthesis)\nb Health days lost were include on this slide to illustrate in relatable terms the magnitude of health loss associated with QAL Y decrements. Healthy days lost \ncalculated by multiplying QALY decrement by 365. \nc Alternate values are inverse variance weighted values from Tang et al. 2021 J Pub Health. Source material places higher decre ment on outpatient disease \nthan inpatient disease for age 65+.Pneumococcal Disease \nTreatment Intensity, AgeQALY \nDecrement\nOutpatient, 19 -64 0.0094\nInpatient, 19 -64 0.0396\nOutpatient, 65+ 0.0586\nInpatient, 65+ 0.0087Alternate Utility Decrementsc\n41Baseline QAL Y Values\nAge General CMC/IC\n50-55 0.83 (0.78,0.88) 0.72 (0.67,0.77)\n56-60 0.81 (0.76,0.86) 0.69 (0.64,0.74)\n61-65 0.77 (0.72,0.82) 0.63 (0.58,0.68)\n66-70 0.76 (0.71,0.81) 0.57 (0.52,0.62)\n71-75 0.74 (0.69,0.79) 0.54 (0.49,0.59)\n76-80 0.7 (0.65,0.75) 0.52 (0.47,0.57)\n81-85 0.63 (0.58,0.68) 0.51 (0.46,0.56)\n86+ 0.51 (0.46,0.56) 0.51 (0.46,0.56)\nSisk, 2003.\n42Disease Cost (2023$)\nData for ages 19 -64 from MarketScan  2019 -2022. Data for 65+ from CMS Medicare claims 2019 -2022.  95% CI from bootstrapping mean values with 1,000 \niterations. All costs converted to 2023$ using CPI Medical Care before bootstrapping. See appendix slide for ICD -10 codes.Disease Setting Cost 95% CI\n19-64 YearsIPD IPT $64,018.10 $61,559.31 $66,424.61\nNBP IPT $58,423.99 $55,923.53 $60,908.13\nNBP OPT $362.38 $339.44 $385.24\n65+ YearsIPD IPT $27,564.22 $27,039.18 $28,149.20\nNBP IPT $21,300.64 $20,825.64 $21,800.98\nNBP OPT $318.22 $308.06 $328.70\n43ICD -10 Codes for Medical Cost Extraction\nDisease ICD-10 Codes\nIPD A40.3, A40.9+B95.3, A41.9+B95.3, R78.81+B95.3, G00.1, G00.2+B95.3, \nG00.9+B95.3, G03.9+B95.3, J86.x+B95.3, J85.1+B95.3, A40.3 + at least one code \nfrom \"All -cause\", A40.9+B95.3 + at least one code from \"All -cause\", \nA41.9+B95.3 + at least one code from \"All -cause\", R78.81+B95.3 + at least one \ncode from \"All -cause\", A40.9 & J13, A41.9 & J13, R78.81 & J13, M00.1x, \nK65.8+B95.3, I30.1+B95.3, I33.0+B95.3, I33.9 +B95.3, K65.2+B95.3, \nM86.1x/M86.2x/M86.9+B95.3, M00.0x, M00.2x, M00.8x, M00.9 + B95.3\nNBP J13, J15.9+B95.3, J18.0/J18.1+B95.3, J18.8/J18.9+B95.3\nAll-cause (for \nsatisfying some \ndefinitions of \nIPD)J12.x (J12.0, J12.1, J12.2, J12.3, J12.81, J12.89, J12.9), J13, J18.1, A48.1, J14, J15.0, \nJ15.1, J15.2x (J15.20, J15.211, J15.212, J15.29), J15.3, J15.4, J15.5, J15.6, J15.8, \nJ15.9, J15.7, J16.x (J16.0, J16.8), A22.1, A37.X1, B25.0, B44.0, J17, J18.0, J18.2, \nJ18.8, J18.9, J09.X1, J10.0x (J10.00, J10.01, J10.08), J11.0x (J11.00, J11.08)\n44Work Loss\nAgeLabor Force \nParticipation \nRate (%)aMedian Daily \nWage ($)b\n19 to 24 71 99.71\n25 to 34 83.2 148.86\n35 to 44 83 175.57\n45 to 54 81.1 176.14\n55 to 64 65.2 169.43\n65 to 74 26.6 157.29\n75+ 8.2 157.29\na US Bureau of Labor Statistics. \nb Current Population Survey, 2023.\nc Altawalbeh  SM, Wateska  AR, Nowalk  MP, Lin CJ, Harrison LH, Schaffner W, Zimmerman RK, Smith KJ. Societal cost of racial pneumococcal disease disparities in \nUS adults aged 50 years or older. Applied Health Economics and Health Policy. 2024 Jan;22(1):61 -71.\nd Used ratio of days of work loss from outpatient (14) to inpatient pneumonia (18) allowed by Marine Corps policy and applied t o inpatient durations of illness \nfrom Altawalbeh  2024. Vold  Pepper P, Owens DK. Cost -effectiveness of the pneumococcal vaccine in the United States Navy and Marine Corps. Clinical \ninfectious diseases. 2000 Jan 1;30(1):157 -64.Base High Low\nInpatientc 34 17 51\nOutpatientd 26.4 13.2 39.7Labor Force Participation and Daily Wage Duration of Work Loss\n45Question 1a: Vaccination at age 65 with PCV21\nSerotype 4 \n@ 5%Serotype 4 \n@ 10%Serotype 4 \n@ 15%Serotype 4 \n@ 20%Serotype 4 \n@ 25%Serotype 4 \n@ 30%Serotype 4 \n@ 35+%\nHealth Outcomes\nIPD Cases -749 -569 -389 -209 -28 152\nHospitalized Pneumonia Cases -1,498 -1,282 -1,067 -852 -637 -422\nNon -hospitalized Pneumonia \nCases-3,350 -2,841 -2,333 -1,824 -1,316 -807\nDeaths due to IPD -91 -69 -47 -25 -4 18\nDeaths due to Pneumonia -55 -47 -39 -32 -24 -16\nQALYs 1,132 897 661 426 191 -45\nLife-years 1,808 1,431 1,055 679 302 -74\nCosts (million $)\nTotal Cost 15 29 43 57 71 85\nMedical Costs -54 -44 -34 -24 -15 -5\nVaccine Costs 90 90 90 90 90 90\nWork Loss -21 -17 -12 -8 -4 1\nCost Ratios ($)\nCost/QALY 13,436 32,640 65,513 134,710 374,763 Dominated Dominated\nCost/Life -year 8,412 20,443 41,059 84,543 236,327 Dominated DominatedCohort of 65 -year -olds.  Comparator is PCV20 at age 65.\nBase case serotype 4 distributions are age, risk, and disease condition specific as displayed earlier in the slides.  They ra nge  from 0 to 9.99%", "summary": "1Economic Assessment of PCV21 in U.S. Adults Charles Stoecker Tulane University School of Public Health and Tropical Medicine ACIP June 27, 2024  2Conflicts of Interest ❑Dr. Stoecker has no conflicts of interest to declare. 3Acronyms ❑ PCV: pneumococcal conjugate vaccine ❑ PCV20: 20 valent PCV ❑ PCV21: 21 valent PCV ❑ VE: vaccine effectiveness ❑ VT: vaccine type ❑ ST: serotype ❑ NBP: non -bacteremic  pneumonia ❑ IPD: invasive pneumococcal disease ❑ IPT: inpatient ❑ OPT: outpatient ❑ QALY:…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/02-Pneumococcal-Stoecker-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 45}
{"title": "03 Pneumococcal Leidner 508", "content": "Summary of three economic analyses on the use of \n21-valent pneumococcal conjugate vaccine (PCV21) \namong adults in the United States\nAndrew J. Leidner, PhD\nApplied Research, Implementation Science and Evaluation (ARISE) Branch\nImmunization Services Division (ISD)\nNCIRD\nACIP Meeting\nJune 27, 2024NCIRD/ISD/ARISE\nThe findings and conclusions in this report are those of the author and do not necessarily represent the views of the Centers  for Disease Control \nand Prevention.1\n•This presentation summarizes work conducted by three modeling teams\n-Tulane -CDC team\n•Charles Stoecker (Tulane University), Yin Wang (Tulane University), Miwako Kobayashi (CDC), Andrew \nLeidner (CDC), Bo-Hyun Cho (CDC), Cheryl Ward (CDC)\n-Merck team\n•Kwame Owusu -Edusei , Zinan  Yi, Elamin  Elbasha , Elmira Flem , Thomas Weiss, Heather Platt, Kristen \nFeemster, Kelly Johnson, Ulrike Buchwald, Craig Roberts, Don Yin\n-Pittsburgh team\n•Shoroq  Altawalbeh , Angela Wateska , Mary Patricia Nowalk , Chyongchiou  Lin, Lee Harrison, William \nShaffner , Richard Zimmerman, Kenneth SmithAcknowledgements\n2Disclaimer: Views and opinions expressed in this presentation are the authors and do not necessarily represent the views and opinions of the \nCenters for Disease Control and Prevention. \n•Andrew Leidner: None\n•Tulane -CDC team: None\n•Merck team:\n-Merck manufactures the PCV21, PCV15 and PPSV23 vaccines\n•Pittsburgh team:\n-From the competing interest section of their articlea: Dr. Wateska  has had a research grant from NIAID in the \npast 3 years. Dr. Nowalk  has had research grants from Merck & Co., Inc. and Sanofi Pasteur in the past 3 years. \nDr. Schaffner has had a research grant from CDC in the past 3 years. Dr. Zimmerman has had research grants \nfrom NIH and Sanofi Pasteur in 3 years. Dr. Smith has had research grants from NIAID and Sanofi Pasteur in the \npast 3 years.Conflicts of interest statement\n3a. Altawalbeh , Shoroq  M., et al. \"Cost -effectiveness of an in -development adult -formulated 21 -valent pneumococcal conjugate vaccine in US adults aged  50 years or \nolder.\" Vaccine 42.12 (2024): 3024 -3032. Link.\nTerminology\n4Abbreviation Full term/Meaning\nCER Cost -effectiveness ratio\nCFR Case -fatality rate\nCMC Chronic medical conditions but not immunocompromised  \nIC Immunocompromising conditions\nICER Incremental cost -effectiveness ratio\nIPD Invasive pneumococcal disease\nNBP Non -bacteremic  pneumonia\nPCV15 15-valent pneumococcal conjugate vaccine\nPCV20 20-valent pneumococcal conjugate vaccine\nPCV21 21-valent pneumococcal conjugate vaccine\nPPSV23 23-valent pneumococcal polysaccharide vaccine\nQALYs Quality -adjusted life -years\n•Background on cost -effectiveness analysis\n•Model overview\n•Main results\n•Model comparison\n•SummaryOutline\n5\n•CEAs compare the costs and outcomes of two or more strategies by estimating a cost -effectiveness \nratio (CER)\n-CER is an estimated cost per unit of health outcome gained\n•Outcomes: averted cases, averted hospitalizations, quality -adjusted life years (QALYs)\n•Cost per QALY gained  ($/QALY)\n-CERs always compare 2 potential strategies\n•E.g., vaccination vs. no vaccination, vaccine schedule A vs. vaccine schedule B, new \nvaccination vs. status quoWhat is cost -effectiveness analysis (CEA)?\n6CostsVaccineA  – CostsVaccineB       Change in costs\n   =                         = $/Outcome\nOutcomesVaccineA  – OutcomesVaccineB          Change in outcomes\n\nWhat is cost -effectiveness analysis (CEA)?\n7CostsVaccineA  – CostsVaccineB                Change in costs\n          =                         = $/Outcome\nOutcomesVaccineA  – OutcomesVaccineB             Change in outcomes\nEconomic model inputs\n  Vaccine characteristics\n     Efficacy\n     Safety\n     Cost per dose\n …\n  Disease burden inputs\n     Incidence rates\n     Health care costs\n     Mortality rates\n                …Economic model estimated  outputs\n   Costs\n      Vaccination program costs\n      Disease -related costs\n   Health outcomes\n      Prevented episodes of disease\n      QALYs gainedEconomic \nmodel\n\nInterpreting a cost -effectiveness ratio\nChange in costs\n                                          = $/Outcome\nChange in outcomes\nQuadrant II:\nDominatedQuadrant I:\nHigher costs & \nhigher health\nQuadrant III:\nLower costs & \nlower healthQuadrant IV:\nCost -savingBetter health outcomes\n(Change in outcomes > 0)Worse health outcomes\n(Change in outcomes < 0)Higher costs\n(Change in costs > 0)\nLower costs\n(Change in costs < 0)\nVB\n8 VB= VaccineB\n•Background on cost -effectiveness analysis\n•Model overview\n•Main results\n•Model comparison\n•SummaryOutline\n9\nModel overview\n10 a.In this presentation, all cost -effectiveness ratios that were reported in the Pittsburgh model have been adjusted to US$2023 (from  US$2019) for consistency with the other models.Model characteristics Tulane -CDC Merck Pittsburgh\nCohort type Single cohort Multi -cohort Single cohort\nAnalytic model time frame Lifetime Lifetime Lifetime\nBase case perspective Limited societal Societal Societal & healthcare sector\nCurrency year 2023 $ US 2023 $ US 2019 $ USa\nVaccine cost PCV20: $289\nPCV21: $319PCV20: $261\nPCV21: $287PCV20: $249\nPCV21: $333\nOther vaccine costs per doseAdmin: $30; \ntravel: $36Admin: $19 Admin: $24; \nadverse events: $0.76 \nHow many years following a PCV dose \nuntil protections wanes to 0%15 years 15 years15 years for NBP\n20 years for IPD\nCirculating serotype protection ratio: \nPCV21:PCV202.7 to 9.5 \n(vaccine -unique types)2.9 to 6.3\n(vaccine -unique types)1.5 to 1.6 \n(all types)\nModel overview, cont.\n11Model characteristics Tulane -CDC Merck Pittsburgh\nInclude indirect effects from pediatric PCV20 use YesIn sensitivity \nanalysesIn sensitivity \nanalyses\nIndirect effects magnitude, when included84% reduction \nby year 633% reduction by \nyear 550% reduction \nby year 1\nSeparately models disability sequalae, post -IPD NoaYes Yes\nSeparately models disability sequalae, post -NBP NoaNo Yes\nInclude age -adjusted incidence Yes Yes Yes\nInclude risk -stratified incidence groups General/CMC/IC General/CMC/ICBlack/Non -black & \nGeneral/Smoking/\nCMC/IC\nCase -fatality -rates (CFRs), inpatient pneumonia (NBP) \n(%, among 50 -64 year olds)3 to 4b3b4 to 6b\nProductivity loss for disease -related deaths adjusted by \nemployment status, varies by ageYes No No\na.In the Tulane -CDC model, inpatient disease burden assumptions includes a portion of the disease burden from disability sequalae, u p to 1 year for QALY loss and up to 6 months for costs.\nb.For the Tulane -CDC and Merck model, NBP CFRs were based on National Inpatient Sample (i.e., hospital discharge) data, and in the Pi ttsburgh model NBP CFRs were assumed to be 50% of the rate of IPD CFRs.\nPolicy question 1: Currently recommended adults\nBase case estimates ($/QALY)\n12Intervention Comparator Tulane -CDC Merck Pittsburgh\nAge-based vaccination \nat 65 with PCV21Age-based vaccination \nat 65 with PCV204,309\n(Cost -saving to $18,599)a5,090\nCost -saving to \n58,116b,cRisk-based vaccination \nwith PCV21Risk-based vaccination \nwith PCV20Cost -Saving\n(Range was cost -saving)aCost -saving\na.This range was estimated using probabilistic sensitivity analyses, where all inputs were varied.\nb.The Pittsburgh model assessed age -based and risk -based use in the same analysis, so strategies with age -based use at age 65 also in cluded risk -based use from age 50 to 64.\nc.These  ICER values were calculated by the CDC ACIP economic review team from costs and effectiveness values reported in the Pittsbur g model. High range value comes from healthcare sector perspective; low range \nvalue comes from societal perspective.•PCV21 protection against circulating serotypes is greater, and PCV21 is modestly more \nexpensive than PCV20\nPolicy question 2: Age 50 -64\nBase case estimates ($/QALY)\n13Intervention Comparator Tulane -CDC Merck Pittsburgh\nAge-based vaccination \nat 50 and 65 with PCV21Age-based vaccination \nat 65 with PCV21b269,643\n($198,098 to $701,066)a105,303 to \n256,318b2,713 to \n114,645c\nAge-based vaccination \nat 50 and 65 with PCV20Age-based vaccination at 65 \nand risk -based vaccination at \n50-64 with PCV20628,473 NAd36,854 to \n149,269c\na.This range was estimated using probabilistic sensitivity analyses, where all inputs were varied.\nb.The Merck model assessed PCV21 use at age 50 and 65 vs PCV21 use at age 65 among general risk (i.e., not CMC or IC) populations a nd PCV20 use among CMC/IC populations. High range value comes from a scenario \nwith indirect effects and without productivity loss from disease -induced death; low range value comes from a scenario without in direct effects and with productivity loss from disease -induced death.\nc.These  ICER values were calculated by the CDC ACIP economic review team from costs and effectiveness values reported in the Pittsbur g model. High range value comes from healthcare sector perspective; low range \nvalue comes from societal perspective.\nd. The Merck model did not assess lowering the age -based recommendation to 50 for the use of PCV20.•Higher ICERs than for the currently recommended group because younger ages have lower \ndisease burden\n•PCV21 protection against circulating serotypes is greater\n•PCV20 preventable disease burden is impacted by indirect effects\n•Substantial variation in estimates within models, across models and across vaccines\nPolicy question 3: Age 19 -49\nBase case estimates ($/QALY)\n14Intervention Comparator Tulane -CDC Merck\nAge-based vaccination \nat 19 with PCV21 (Tulane -CDC); or \nat 19 and 65 with PCV21 (Merck)bAge-based vaccination \nat 50 with PCV21 (Tulane -CDC);\nor at 65 with PCV20 (Merck)bDominated\n(Range was dominated)a647,569b\nNotes : The Pittsburgh model did not assess strategies for individuals younger than 50 years. Across all models, the use of PCV20 w as not directly assessed for 19 -50-year -olds.\na.This range was estimated using probabilistic sensitivity analyses, where all inputs were varied.\nb.The Merck model intervention strategy was PCV21 at age 19 and 65 and the comparator was PCV20 at age 65.•Higher ICERs (or “dominated” interventions) than for currently recommended adult or age \n50 strategies because younger ages have lower disease burden\nSupplemental dose\nBase case estimates ($/QALY)\n15Intervention Comparator Tulane -CDC Merck\nSupplemental dose with PCV21 \namong individuals who have \nreceived PCV20 No supplemental dose \nwith PCV21206,191 to \n442,010a274,844 to \n512,266b\nNote: The Pittsburgh model did not assess supplemental PCV21 dose. \na.Range  depends on whether a person received PCV20 because of age -based or risk -based recommendation and the time since PCV20, where ri sk-based vaccinees with a longer duration since PCV20 had lower costs. \nb.Range  depends on age and time since PCV20; high value assumed age 65 general population (i.e., no CMC or IC) and older and 2 years since PCV20; low value assumed age 50 -64 CMC/IC population and 5 years since \nPCV20.•Higher ICERs than for the currently recommended adult strategies because individuals \npreviously vaccinated with PCV20 have lower disease burden due to PCV20 vaccine \nprotection\n•Variation in estimates due to duration between supplemental PCV21 dose and the previous \ndose of PCV20, and due to differences in disease burden by age and risk group\n•Background on cost -effectiveness analysis\n•Model overview\n•Main results\n•Model comparison\n•SummaryOutline\n16\nSensitivity/scenario analyses\nWhat if selected Pittsburgh model assumptions were more similar to the Tulane -CDC model?\n17Base case \n(Pittsburgh model)\nIncluding PCV20 \nindirect effects\nPCV20 indirect effects \nand no disability\nPCV20 indirect effects, \nno disability, and lower \nNBP CFR\nBase case \n(Tulane -CDC model)\n -  50,000  100,000  150,000  200,000  250,000  300,000  350,000  400,000  450,000  500,000\nIncremental cost -effectiveness ratio (ICER) ($/QALY)Policy Question 2: Age 50 -64\nCost -effectiveness estimates\nIn the Pittsburgh model results, lower ICERs are from the societal perspective, higher ICERs are from the health care sector perspective.\nPolicy question 2: Age 50 -64\nBase case estimates ($/QALY)\n18Intervention Comparator Tulane -CDC Merck Pittsburgh\nAge-based vaccination \nat 50 and 65 with PCV21Age-based vaccination \nat 65 with PCV21b269,643\n($198,098 to $701,066)a105,303 to \n256,318b2,713 to \n114,645c\nAge-based vaccination \nat 50 and 65 with PCV20Age-based vaccination at 65 and \nrisk-based vaccination at 50 -64 \nwith PCV20628,473 NAd36,854 to \n149,269c\na.This range was estimated using probabilistic sensitivity analyses, where all inputs were varied.\nb.The Merck model assessed PCV21 use at age 50 and 65 vs PCV21 use at age 65 among general risk (i.e., no CMC or IC) populations an d PCV20 use among CMC/IC populations. High range value comes from a scenario \nwith indirect effects and without productivity loss from disease -induced death; low range value comes from a scenario without in direct effects and with productivity loss from disease -induced death.\nc.These  ICER values were calculated by the CDC ACIP economic review team from costs and effectiveness values reported in the Pittsbur g model. High range value comes from healthcare sector perspective; low range \nvalue comes from societal perspective.\nd. The Merck model did not assess lowering the age -based recommendation to 50 for the use of PCV20.•Comparison summary Tulane -CDC vs. Pittsburgh\n-Not including PCV20 indirect effects, including long -term disability disease states, and higher pneumonia \nCFR assumptions yield more favorable (i.e., lower) CERs\n-Other factors include the magnitudes of indirect effect assumptions and productivity losses\n•Limited data available on vaccine efficacy and duration of protection\n•Uncertainties about several model inputs and assumptions \n-Future epidemiology of pneumococcal serotypes that are not included in PCV21 (e.g., serotype 4, 19F)\n-Indirect effects from pediatric PCV20 use\n-Prevalence and severity of disability sequalae\n-Vaccine price  \n•Merck model base case input for PCV21 cost per dose was $287, which has also been announced publicly as \nthe list pricea\n•Potential challenges to vaccination implementation due to changing the pneumococcal \nvaccine schedule were not includedLimitations\n19a.US FDA approves Merck's pneumococcal vaccine for adults | Reuters\nSummary of model findings\n20Policy question \npopulations Strategy details Summary across available models\n1. Currently \nrecommended \nadultsAge-based PCV21 Cost -saving to $58,000 per QALY gained\nRisk-based PCV21 Cost -saving in all three models\n2. Ages 50 -64PCV21 $3,000 to $270,000 per QALY gained \nPCV20 $37,000 to $630,000 per QALY gained\n3. Ages 19 -49 PCV21 $650,000 per QALY gained to “Dominated”\nSupplemental dose Supplemental dose with PCV21 $210,000 to $510,000 per QALY gained\n•As modeled, most strategies improved health \n-Age-based vaccination at 19 years instead of 50 years in the Tulane -CDC model did not improve health\n•Several strategies were cost -saving\n•Variability in estimates across models for age 50 and supplemental dose strategies\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention.\nThank you for your attention and thank you to those that contributed to this presentation\n21Tulane -CDC team\nCharles Stoecker (Tulane University)\nYin Wang (Tulane University) \nMiwako Kobayashi (CDC) \nAndrew Leidner (CDC)\nBo-Hyun Cho (CDC)\nCheryl Ward (CDC)Merck team\nKwame Owusu -Edusei\nZinan  Yi\nElamin  Elbasha\nElmira Flem\nThomas Weiss\nHeather Platt\nKristen Feemster\nKelly Johnson\nUlrike Buchwald\nCraig Roberts\nDon YinPittsburgh team\nShoroq  Altawalbeh\nAngela Wateska\nMary Patricia Nowalk\nChyongchiou  Lin\nLee Harrison\nWilliam Shaffner\nRichard Zimmerman\nKenneth SmithACIP economics review team\nAustin Williams\nFangjun Zhou\nBo-Hyun Cho\nJamie Pike\nReni Kaul\nXiaoyu Dong", "summary": "Summary of three economic analyses on the use of  21-valent pneumococcal conjugate vaccine (PCV21)  among adults in the United States Andrew J. Leidner, PhD Applied Research, Implementation Science and Evaluation (ARISE) Branch Immunization Services Division (ISD) NCIRD ACIP Meeting June 27, 2024NCIRD/ISD/ARISE The findings and conclusions in this report are those of the author and do not necessarily represent the views of the Centers  for Disease Control  and Prevention.1 •This presentation…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/03-Pneumococcal-Leidner-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 21}
{"title": "04 Pneumococcal Kobayashi 508", "content": "Centers for Disease Control and Prevention \nNational Center for Immunization and Respiratory Diseases \nSummary of Work Group Interpretations of EtR and \nPolicy Option on PCV21 Use in Adults \nJune 2024, ACIP Meeting \nJune 27, 2024 \nMiwako Kobayashi, MD, MPH, FACP , FIDSA \nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences. \n\n  \n   \n  \n   \n     \n               Policy Questions Being Considered by the Work Group \n1. Should PCV21 be recommended for U.S. adults aged ≥19 years who \ncurrently have a recommendation to receive a PCV*? (Group 1) \nComparison (current recommendations): \n▪PCV -naïve adults aged ≥19 years \nPCV20 OR PLUS PCV15 PPSV23† \n† If adults previously received PPSV23 before receiving a dose of PCV15, it need not be followed by another dose of PPSV23 \n▪PCV -experienced adults aged ≥19 years who have not completed the recommended series \nPCV20 1≥ dose of \nPPSV23 OR \n*Includes: \n• Adults aged ≥65 years who have never received a PCV \n• Adults aged 19 -64 years with a risk condition, who have never received a PCV \n• Adults aged ≥19 year who have received a PCV (i.e., PCV7 or PCV13), but have not completed the recommended series \n• PCV20 use based on shared clinical decision -making for adults ≥65 years who have \n  2 completed the recommended series with PCV13 and PPSV23 \n  Policy Questions Being Considered by the Work Group \n2. Should PCV21 be recommended for U.S. adults aged 50 -64 years who \ncurrently do not have a risk -based pneumococcal vaccine indication? \n(Group 2) \n3. Should PCV21 be recommended for U.S. adults aged 19 -49 years who \ncurrently do not have a risk -based pneumococcal vaccine indication? \n(Group 3) \n▪Questions 2 and 3 imply a new age -based recommendation for these age groups. \nComparison (current recommendation): \n▪No vaccine \n3 \n \n \n \n  \n   \n  \n \nEvidence to Recommendations ( EtR ) framework \n4 EtR Domain Question \nPublic Health Problem • Is the problem of public health importance? \nBenefits and Harms • How substantial are the desirable anticipated effects? \n• How substantial are the undesirable anticipated effects? \n• Do the desirable effects outweigh the undesirable effects? \n• What is the overall certainty of this evidence for the critical outcomes? \nValues • Does the target population feel the desirable effects are large relative to \nthe undesirable effects? \n• Is there important variability in how patients value the outcomes? \nAcceptability • Is the intervention acceptable to key stakeholders? \nResource Use • Is the intervention a reasonable and efficient allocation of resources? \nFeasibility • Is the intervention feasible to implement? \nEquity • What would be the impact of the intervention on health equity? \n    \n    \n \n    \n \n \n \n \n \n   \n  Summary of Work Group Interpretation of the EtR Domains for EtR \nDomains Public Health Problem, Benefits and Harms, and Equity \nEtR Domains Group 1. Adults with \ncurrent PCV \nrecommendations Group 2. Adults aged \n50–64 years, no risk -\nbased indication Group 3. Adults aged \n19–49 years, no risk -\nbased indication \nPublic Health Problem Yes Probably Yes No/Probably No \nBenefits and Harms \na. Benefits Moderate/Large Small/Moderate Minimal/Small \nb. Harms Minimal \nc. Benefit>Harm? Favors PCV21 use Favors PCV21/Favors no \nvaccine (split) \nd. Overall certainty: effectiveness Moderate \ne. Overall certainty: safety Moderate \nEquity Probably increased \n5Kobayashi February 2024 ACIP meeting presentation \n \n   \n  \nEvidence to Recommendations ( EtR ) framework \n6 EtR Domain Question \nValues • Does the target population feel the desirable effects are large relative to \nthe undesirable effects? \n• Is there important variability in how patients value the outcomes? \nAcceptability • Is the intervention acceptable to key stakeholders? \nResource Use • Is the intervention a reasonable and efficient allocation of resources? \nFeasibility • Is the intervention feasible to implement? \n \n \n \n \n \n EtR Values and Preferences \n• Does the population feel that the desirable effects are large relative to \nundesirable effects? \n• Is there important uncertainty about or variability in how much people \nvalue the main outcomes*? \nOutcomes \n= Vaccine -type (VT) invasive pneumococcal disease (IPD), VT -non -bacteremic \npneumococcal pneumonia, VT -pneumococcal deaths, serious adverse events (SAEs) \n\n \n 14 17 10 7 38 45 \n46 47 37 32 37 38 11 6 7 8 \n0 10 20 30 40 50 60 70 80 90 100 \nage <5 years age 19-49 years age 50-64 years age ≥ 65 years   \n \n  The proportion of IPD cases due to PCV20/non -PCV21 \nserotypes is relatively lower in older vs younger adults \nProportion of IPD by vaccine -type and age group, 2018−2022 \nPCV20/ non-PCV21 PCV20 and PCV21 PCV21/ non-PCV20 NVT \n8CDCsActive Bacterial Core surveillance \n   \n \n  54–62 % of IPD cases in adults were due to PCV20 serotypes \nProportion of IPD by vaccine -type and age group, 2018−2022 \n100 \n90 \n80 \n70 \n60 \n50 \n40 \n30 \n20 \n10 \n0 11 6 7 8 \n37 32 37 38 \n38 45 \n46 47 62% 56% 54% \n14 17 10 7 \nage <5 years age 19-49 years age 50-64 years age ≥ 65 years \nPCV20/ non-PCV21 PCV20 and PCV21 PCV21/ non-PCV20 NVT \nCDCsActive Bacterial Core surveillance 9 \n   Proportion of IPD by vaccine- type and age group, 2018−2022 \n100 \n90 \n80 \n70 \n60 \n50 \n40 \n30 \n20 \n10 \n0 11 6 7 8 \n37 32 37 38 \n77% 83% 85% \n38 62% 45 \n46 4756% 54% \n14 17 10 7 \nage <5 years age 19-49 years age 50-64 years age ≥ 65 years \nPCV20/ non-PCV21  \n  77–85% of IPD cases in adults were due to PCV21 serotypes \nPCV20 a  nd PCV21 PCV21/ non-PCV20 NVT \nCDCsActive Bacterial Core surveillance \n10 \n    \n        \n       \n        \n     \n    GRADE Summary of Findings Table \n1: Adults currently recommended to receive PCV \na. These are all immunogenicity studies and there are no correlates of protection for some critical outcomes considered. \nb. Noninferiority for GMT ratio was defined as the lower bound of the 95% CI of the estimated OPA GMT ratio ({PCV21:PPSV23} to b e > 0.33. \nc. Superiority for GMT ratio was defined as the lower bound of the 95% CI of the estimated OPA GMT ratio [PCV21:PPSV23] to be > 1.0. \nd. Noninferiority for GMT ratio was defined as the lower bound of the 2 sided 95% CI of the OPA GMT ratio [PCV21 / PCV20] to be >0.5. \ne. Superiority for GMT ratio was defined as the lower bound of the 2 sided 95% CI of the OPA GMT ratio [PCV21 / PCV20] to be >2. 0. \nKobayashi February 2024 ACIP meeting presentation \n11 \n  \n            \n  \n    GRADE Summary of Findings Table \n1: Adults currently recommended to receive PCV \nf. few vaccine -related serious adverse events reported. \ng. Bronchospasm (V116 -005): 50 -year-old female in the sequential group with bronchospasm within 30 minutes after the 2ndvaccination (V116); duration 23 hours; resolved; Injection site cellulitis (V116 -006): 67 -year-old female in Cohort 1 (prior PPSV23) with i njection site cellulitis \non Day 6; duration 1.57 weeks; resolved (Merck, unpublished). \nKobayashi February 2024 ACIP meeting presentation \n12 \n \n  \n  \n     \n           \n          \n       \n   \n13 Recommendation by a healthcare provider was among the top \nreasons influencing the likelihood of receiving a pneumococcal \nvaccine \n▪Recommendation by a healthcare provider was one of the top factors \ninfluencing the likelihood of receiving a pneumococcal vaccine1, 2 \n▪Among adults aged 19–64 years with risk -based indications , the top reasons \nfor not getting a pneumococcal vaccine were2: \n• Not knowing a pneumococcal vaccine was needed (32%) \n• Never receiving a recommendation by a healthcare provider (28%) \n1. Online survey conducted in February 2024, funded by Merck. The survey targeted 250 adults aged ≥65 years who previously recei ved a pneumococcal vaccine as an adult and \n250 adults aged 50 –64 years (healthy & CMC) who have not previously received a pneumococcal vaccine as an adult. Participants we re being “in favor” or “neutral” toward \nadult vaccinations \n2. Online survey conducted in January 2024, by HaPPI Survey Collaborative. The survey Targeted adults aged 19 –64 years with underlying conditions (self -report) with \nindications for risk -based pneumococcal vaccine indications \n   \n    Does the population feel that the desirable effects are large \nrelative to undesirable effects? \n▪The Work Group found it challenging to interpret this EtR domain due to limited data \n1. Adults currently 2. Adults aged 50 –64 years with 3. Adults aged 19 –49 years \nrecommended to receive PCV no risk -based indication with no risk -based indication \n □  No \n□  Probably no  \n□  Probably yes  \n□  Yes  \n□  Varies  \n□  Don’t know   □  No \n□  Probably no  \n□  Probably yes  \n□  Yes  \n□  Varies  \n□  Don’t know   \nMinority opinion   No \n  Probably no  \n  Probably yes\n  Yes  \n  Varies  \n  Don’t know   \n  \n      Is there important uncertainty about or variability in how \nmuch people value the main outcomes*? \n1. Adults currently recommended to receive PCV \n□  Important uncertainty or variability \n□  Probably important uncertainty or variability \n□  Probably not important uncertainty or variability  \n□  No important uncertainty or variability  \n□  No known undesirable outcomes \n15* Vaccine -type (VT) IPD, VT -non -bacteremic pneumococcal pneumonia, VT -pneumococcal deaths, serious adverse events \n  \n      \n  Probably important uncertainty or variability \n  Probably not important uncertainty or variability  \n  \n Is there important uncertainty about or variability in how \nmuch people value the main outcomes*? \n2. Adults aged 50 –64 years with no risk -based indication \n□ Important uncertainty or variability \n□\n□\n□ No important uncertainty or variability \n□ No known undesirable outcomes \n16*Vaccine -type (VT) IPD, VT -non -bacteremic pneumococcal pneumonia, VT -pneumococcal deaths, serious adverse events \n    \n       \n \n  \n  \n Is there important uncertainty about or variability in how \nmuch people value the main outcomes*? \n3. Adults aged 19 –49 years with no risk -based indication \n□ Important uncertainty or variability \n□ Probably important uncertainty or variability \n□ Probably not important uncertainty or variability \n□ No important uncertainty or variability \n□ No known undesirable outcomes \n* Vaccine -type (VT) IPD, VT -non -bacteremic pneumococcal pneumonia, VT -pneumococcal deaths, serious adverse events \n17 \n EtR Acceptability \n• Is the intervention acceptable to key stakeholders*? \nKey Stakeholders \n= healthcare providers, healthcare delivery systems, the public  \n  \n \n \n \n \n \n   \n \n    \n        \n  Online surveys among healthcare providers to understand \nvaccine preference \n▪Expressed more challenges in identifying patients eligible for pneumococcal \nvaccination based on risk factors vs age1 \n• Focus during visit is on other priorities during the visit (e.g., other vaccinations, \ntreatment, counseling) \n• Most commonly identified challenge among physicians and NP/PAs \n• Unknown pneumococcal vaccination history of the patient \n• Unknown underlying health condition of patient \n• Most commonly identified challenge among pharmacists \n▪Providers reported they were slightly likely (32%), likely (39%), or extremely likely \n(19%) to support ACIP lowering the age -based recommendation for pneumococcal \nvaccines from adults aged ≥65 years to ≥50 years2 \n1. Online survey conducted in February 2024 by ZS, funded by Merck. 502 HCPs (physicians, NP/PAs, pharmacists who vaccinate) par tic\n19 ipated; majority (70%) physicians \n2. Online survey conducted from March –May 2024 by OPEN Health, funded by Merck. Included a total of 340 HCPs consisting of physicia ns, nurse practitioners, pnysician \nassistants, and pharmacists \n   Is the intervention acceptable to key stakeholders? \n1. Adults currently 2. Adults aged 50 –64 years with 3. Adults aged 19 –49 years \nrecommended to receive PCV no risk -based indication with no risk -based indication \n□  No \n□  Probably no  \n□  Probably yes  \n□  Yes  \n□  Varies  \n□  Don’t know   □  No \n□  Probably no  \n□  Probably yes  \n□  Yes  \n□  Varies  \n□  Don’t know   □  No \n□  Probably no  \n□  Probably yes  \n□  Yes  \n□  Varies  \n□  Don’t know   \nMinority opinion \n 20 \n EtR Resource Use \n• Is PCV21 use a reasonable and efficient allocation of resources for adults? \n\n \n  \n  \n   \n \n \n   Summary of findings from economic analysis \nPolicy question \npopulations Strategy details Summary across available models \n1. Currently \nrecommended adults Age -based PCV21 Cost -saving to $58,000 per QAL Y \ngained \nRisk -based PCV21 Cost -saving in all three models \n2. Ages 50 –64 years PCV21 $3,000 to $270,000 per QAL Y gained \nPCV20 $37,000 to $630,000 per QAL Y gained \n3. Ages 19 –49 years PCV21 $650,000 per QAL Y gained to \n“Dominated” \nSupplemental dose Supplemental dose with \nPCV21 $210,000 to $510,000 per QAL Y \ngained \nLeidner June 2024 ACIP meeting presentation \n22 \n \n \n  \n   \n \n \n  Summary of findings from economic analysis \nPolicy question \npopulations Strategy details Summary across available models \n1. Currently \nrecommended adults Age -based PCV21 Cost -saving to $58,000 per QAL Y \ngained \nRisk -based PCV21 Cost -saving in all three models \n2. Ages 50 –64 years PCV21 $3,000 to $270,000 per QAL Y gained \nPCV20 $37,000 to $630,000 per QAL Y gained \n3. Ages 19 –49 years PCV21 $650,000 per QAL Y gained to \n“Dominated” \nSupplemental dose Revaccination with PCV21 $210,000 to $510,000 per QAL Y \ngained \n23 \n \n \n  \n   \n \n \n  Summary of findings from economic analysis \nPolicy question \npopulations Strategy details Summary across available models \n1. Currently \nrecommended adults Age -based PCV21 Cost -saving to $58,000 per QAL Y \ngained \nRisk -based PCV21 Cost -saving in all three models \n2. Ages 50 –64 years PCV21 $3,000 to $270,000 per QAL Y gained \nPCV20 $37,000 to $630,000 per QAL Y gained \n3. Ages 19 –49 years PCV21 $650,000 per QAL Y gained to \n“Dominated” \nSupplemental dose Revaccination with PCV21 $210,000 to $510,000 per QAL Y \ngained \n24 \n \n \n \n \n    Is PCV21 use a reasonable and efficient allocation of \nresources for adults? \n1. Adults currently 2. Adults aged 50 –64 years with 3. Adults aged 19 –49 years \nrecommended to receive PCV no risk -based indication with no risk -based indication \n□ No \nProbably no  \nProbably yes  \n□  Yes  \nVaries  \nDon’t know   □ \n□ \n□ \n□ □  No \n□  Probably no  \n□  Probably yes  \n□  Yes  \n□  Varies  \n□  Don’t know   \n25 □  No \n□  Probably no  \n□  Probably yes  \n□  Yes  \n□  Varies  \n□  Don’t know   \nMinority opinion \n \n EtR Feasibility \n• Is PCV21 use feasible to implement? \nConsiderations: \nFinancial barriers, simplicity and integration, access \n   \n   \n \n \n \n \n \n  \n \n \n \n \n  \n \n \n \n \n    Is PCV21 feasible to implement? \n▪WG interpretation of feasibility generally mirrors interpretation for resource use. \n▪Some expressed the interpretation of group 2 may depend on whether there are \ndifferent age -based recommendations for PCV21 and other PCVs \n1. Adults currently 2. Adults aged 50 –64 years with 3. Adults aged 19 –49 years \nrecommended to receive PCV no risk -based indication with no risk -based indication \n□ \n□\n□\n□\n□□No \nProbably no  \nProbably yes  \nYes  \nVaries  \nDon’t know    \n \n \n \n \n27 □\n□□\n□\n□□ No \nProbably no  \nProbably yes  \nYes  \nVaries  \nDon’t know    \n \n \n \n □\n□\n□□□ No \nProbably no  \nProbably yes  \nYes  \nVaries  \nDon’t know   □ \n \n \n \n \n    \n  \n \n \n \n \n \n \nEquity Probably increased    \n–\n-–\n-\nSummary of Work Group Interpretation of the EtR Domains \nEtR Domains Group 1. Adults with current PCV \nrecommendations Group 2. Adults aged 50 64 \nyears, no risk based indication Group 3. Adults aged 19 49 \nyears, no risk based indication \nPublic Health Problem Yes Probably Yes No/Probably No \nBenefits and Harms \na. Benefits Moderate/Large Small/Moderate Minimal/Small \nb. Harms Minimal \nc. Benefit>Harm? \nd. Overall certainty: effectiveness Favors PCV21 use \nModerate Favors PCV21/Favors no \nvaccine (split) \ne. Overall certainty: safety Moderate \n \n28 Values and Preferences \n a. Desirable>Undesirable? Probably Yes Probably Yes Varies \n b. Uncertainty? Probably important/not important Probably important Important/Probably important\nuncertainty uncertainty uncertainty \nAcceptability Yes Probably Yes Probably No/No \nResource Use Yes Yes/Probably Yes No \nFeasibility Yes Yes/Probably Yes Probably No/No \n \n \n  \n     \n   \n   \n \nSummary: Work Group Interpretation \n1. Should PCV21 be recommended for U.S. adults aged ≥19 years who currently have a \nrecommendation to receive a PCV*? \n*Includes: \n• Adults aged ≥65 years who have never received a PCV \n• Adults aged 19 –64 years with a risk condition, who have never received a PCV \n• Adults aged ≥19 year who have received a PCV (i.e., PCV7 or PCV13), but have not completed the recommended series \n• PCV20 use based on shared clinical decision -making for adults ≥65 years who have completed the recommended series with \nPCV13 and PPSV23 \nBalance of \nconsequences Undesirable \nconsequences \nclearly \noutweigh \ndesirable \nconsequences \nin most \nsettings Undesirable \nconsequences \nprobably \noutweigh \ndesirable \nconsequences \nin most \nsettings The balance \nbetween \ndesirable and \nundesirable \nconsequences \nis closely \nbalanced or \nuncertain Desirable \nconsequences \nprobably \noutweigh \nundesirable \nconsequences \nin most \nsettings Desirable \nconsequences \nclearly \noutweigh \nundesirable \nconsequences \nin most \nsettings There is \ninsufficient \nevidence to \ndetermine the \nbalance of \nconsequences \n29 \n     \n     \n   \n  \nSummary: Work Group Interpretation \n2. Should PCV21 be recommended for U.S. adults aged 50–64 years who currently do \nnot have a risk -based pneumococcal vaccine indication? \n• “Desirable consequences probably outweigh undesirable consequences in most settings ” was selected the most, \nbut did not reach the majority \n• Some selected “Desirable consequences clearly outweigh undesirable consequences “ and “The balance between \ndesirable and undesirable consequences is closely balanced or uncertain ”, but few believed that undesirable \nconsequences outweighed desirable consequences. \nBalance of \nconsequences Undesirable \nconsequences \nclearly \noutweigh \ndesirable \nconsequences \nin most \nsettings Undesirable \nconsequences \nprobably \noutweigh \ndesirable \nconsequences \nin most \nsettings The balance \nbetween \ndesirable and \nundesirable \nconsequences \nis closely \nbalanced or \nuncertain Desirable \nconsequences \nprobably \noutweigh \nundesirable \nconsequences \nin most \nsettings Desirable \nconsequences \nclearly \noutweigh \nundesirable \nconsequences \nin most \nsettings There is \ninsufficient \nevidence to \ndetermine the \nbalance of \nconsequences \n30 \n  \n \nSummary: Work Group Interpretation \n3. Should PCV21 be recommended for U.S. adults aged 19–49 years who currently do \nnot have a risk -based pneumococcal vaccine indication? \n*this implies a new age -based recommendation for adults aged ≥19 years \nBalance of \nconsequences Undesirable \nconsequences \nclearly \noutweigh \ndesirable \nconsequences \nin most \nsettings Undesirable \nconsequences \nprobably \noutweigh \ndesirable \nconsequences \nin most \nsettings The balance \nbetween \ndesirable and \nundesirable \nconsequences \nis closely \nbalanced or \nuncertain Desirable \nconsequences \nprobably \noutweigh \nundesirable \nconsequences \nin most \nsettings Desirable \nconsequences \nclearly \noutweigh \nundesirable \nconsequences \nin most \nsettings There is \ninsufficient \nevidence to \ndetermine the \nbalance of \nconsequences \n31 \n  \n Additional considerations \nWhat would be the impact of recommending PCV21 use for all adults \naged 50 –64 years on health equity? \n\n  \n  \n      Racial disparities due to PCV13 -type IPD decreased after \npediatric PCV13 use \n▪Racial disparities in IPD incidence exist \n▪Remaining disparities in IPD incidence are \nprimarily due to non -PCV13 -type disease \nAdapted from Kobayashi February 2024 ACIP meeting presentation \nFigure: ABCs unpublished data \n1. Vaccination Coverage among Adults in the United States, National Health Interview Survey, 2021 | CDC \n33 \n\n  \n  \n      Racial disparities due to PCV13 -type IPD decreased after \npediatric PCV13 use \n▪Racial disparities in IPD incidence exist \n▪Remaining disparities in IPD incidence are \nprimarily due to non -PCV13 -type disease \nAdapted from Kobayashi February 2024 ACIP meeting presentation \nFigure: ABCs unpublished data \n1. Vaccination Coverage among Adults in the United States, National Health Interview Survey, 2021 | CDC \n34 \n\n    \n  \n   \n  \n  5.9 \nPCV21 \ntype: 8 5% 8.2 \nPCV21 \ntype: 82% 35.5 \n43.2 \n49.0 \npe: 59% ty PCV20 39.1 \ntype: 49% \n9.7 9.5 PCV21 serotypes caused >80% of IPD cases in both Black and White \nadults 50 –64 years; there was a larger difference in % of IPD cases \ncaused by PCV20 serotypes between Black and White adults 50 –64 years \nPCV20/non-PCV21 PCV20 and PCV21 PCV21/non-PCV20 NVT \nPCV20 \nABCs 2018 –2022 unpublished data WHITE BLACK \n35 \n \n     35 IPD rates in Black adults peak at a younger age compared \nwith Non -Black adults \n30 \n25 \n20 \n15 \n10 \n5 \n0 \n40-44 45-49 50-54 55-59 60-64 65+ 40-44 45-49 50-54 55-59 60-64 65+ \nBlack Black Black Black Black Black Non Black Non Black Non Black Non Black Non Black Non Black IPD rate for adults aged ≥65 years across all \nrace/ethnicity (24/100,000) \nABCs 2018 –2019 unpublished data \n36 \n   \n \n     Differences in prevalence of risk conditions among Black vs \nNon -Black adults may be contributing \n▪The proportion of immunocompromised individuals was similar for both racial groups \nat age 50 years and throughout the lifespan \nRacial Disparities in Adult Pneumococcal Vaccination Indications and Pneumococcal Hospitalizations in the U.S -PubMed (nih.gov) \n37 \n   \n \n \n \n \n      \n   Adults with risk -based vaccine indications 19 –64 years had lower \nvaccine coverage compared with adults ≥65 years; differences in vaccine \ncoverage by race/ethnicity existed \nAge group % (95% CI) \nOverall (≥65 years) 65.8 (64.4 -67.2) \nWhite 70.1 (68.8 -71.4) \nBlack 54.8 (50.6 -59.0)* \nHispanic 46.2 (40.9 -51.6)* \nAsian 55.8 (48.7 -62.7)* \nOther 62.5 (53.1 -71.1) \nOverall (19 –64years with risk -based indication ) 22.2 (21.0 -23.5) \nVaccination Coverage among Adults in the United States, National Health Interview Survey, 2021 | CDC \n*p<0.05 for comparisons with White as the reference \n38 \n \n  \n \n \n                  \n     Increase in serotype 4 IPD cases has been reported in \ncertain adult populations in recent years \n▪Serotype 4 is contained in existing pneumococcal vaccines but not PCV21 \n▪Serotype 4 IPD cases had nearly been eliminated after PCV7 use in \nchildren but IPD clusters have been reported in certain populations (e.g., \npeople experiencing homelessness)1,2,3 \n▪In certain areas, increase in serotype 4 IPD cases observed in routine \nsurveillance in recent years, especially post -2020, after near elimination \n• Increase reported in Western United States (Alaska4, Navajo Nation5, ABCs CO/NM/ \nOR sites6) \n▪Appears to primarily affect adults aged <65 years with risk -based \npneumococcal vaccine indications \n1. Callaway et al. MMWR 2023 ; 2. McKee et al. CCDP 2018 ; 3. Beall et al. JID 2021 ; 4. Orell et al. ISPPD 2024; 5\n . Johns Hopkins Center for Indigenous Health and Navajo \nEpidemiology Center 2024 ; 6. CDC Active Bacterial Core surveillance unpublished data 39 \n Summary of  Work Group discussions on lowering \nthe age -based recommendation for PCV21 to age \n≥50 years \n\n \n \n \n  \n  \n  \n Pros and Cons of lowering the age -based recommendation \nfor PCV21 from ≥65 years to ≥50 years \nPros: \n▪Potential to improve vaccine coverage in \nadults aged 50 –64 years who currently have \nrisk-based vaccine indications \n▪Potential to prevent more disease from broad \npneumococcal serotype coverage with PCV21 \n▪Potential to reduce racial disparities in \npneumococcal disease burden given the \ndifferences in when pneumococcal disease \nrates peak and prevalence of conditions that \nincrease the risk of pneumococcal disease \n41 \n  \n    \n \n \n \n \n \n  \n \n  Pros and Cons of lowering the age -based recommendation \nfor PCV21 from ≥65 years to ≥50 years \nCons: \n▪Lack of data on duration of protection from vaccination \n▪Potential unintended consequences of worsening health \nequity by improving access to those who already have \ngood access to healthcare \n▪Higher Cost/QAL Y gained (~270K/QAL Y gained) reported in \nsome economic models \n▪Uncertainties with serotype 4 (serotype contained in \nexisting vaccines but not PCV21) disease trends \n▪Implementation challenges of having different \nrecommendations by product ( i.e, 1 PCV option for adults \n50–64 years without a risk condition; 3 PCV options for \nadults with a risk condition) \n 42 \n   \n   \n \n Summary of WG discussion \n▪The WG agreed that available evidence supports PCV21 use for adults currently \nrecommended to receive a PCV \n▪The WG could not reach a consensus on whether the age -based recommendation for \nPCV21 should be lowered from ≥65 years to ≥50 years \n▪The WG did not support lowering the age -based recommendation for PCV21 to age 19 \nyears \n▪The majority of WG members believed there was insufficient evidence to support \nlowering the age -based recommendation for currently recommended vaccines \n43 \nProposed Voting Language \n\nProposed Voting Language \nACIP recommends PCV21 as an option for adults aged ≥19 years \nwho currently have a recommendation to receive a dose of PCV. \n45 \nClinical Guidance for Implementation \nProposed Language \n\n \n \n   \n  \n \n  \n \n        \n       \n   \n47 PCV -naïve adults (or adults with unknown history) \nA single dose of PCV21 is recommended as an option for all \nadults aged ≥65 years and for adults aged 19 –64 years with \ncertain underlying conditions or risk factors* who have not \nreceived a PCV or whose vaccination history is unknown. \nRationale: \n▪PCV21 is added as an option to the current recommendation to use either PCV20 alone or PCV15 in \nseries with PPSV23 (if PPSV23 not given previously) for these adults; barrier to implementation is likely \nlow. \n▪PCV21 exhibited comparable safety and immunogenicity findings to comparator vaccines in clinical \ntrials. \n▪Economic evaluations were consistently favorable (cost -saving to 58,000 USD/QAL Y gained). \n*Alcoholism; chronic heart, liver, or lung disease; chronic renal failure; cigarette smoking; cochlear implant; congenital or acquired asplenia; cerebrospinal fluid leak; diabetes \nmellitus; generalized malignancy; HIV; Hodgkin disease; immunodeficiency; iatrogenic immunosuppression; leukemia, lymphoma, o r multiple myeloma; nephrotic syndrome; solid \norgan transplant; sickle cell disease; or other hemoglobinopathies. \n  \n \n \n                  \n              \nPCV -naïve adults (or adults with unknown history) \nUnderlying \nconditions Previous \nvaccination \nhistory Age 19 –64 years Age ≥65 years \nNone None No vaccine recommendation PCV21 \nOR \nPCV20 \nOR \nPCV15 ≥1yr PPSV23* \nChronic \nmedical \nconditions None \nPCV21 \nOR \nPCV20 \nOR \n≥8wks† \nPCV15 PPSV23* \n≥1yr \n*If adults previously received PPSV23 before receiving a dose of PCV15, it need not be followed by another dose of PPSV23 \n†A minimum interval of 8 weeks can be considered for adults with an immunocompromising condition, cochlear implant, or cerebro spinal fluid leak CSF leak, \ncochlear \nimplant None \nImmuno -\ncompromised None \n48 \nPneumococcal Vaccine for Adults Aged ≥19 Years: Recommendations of the Advisory Committee on Immunization Practices, United S tates, 2023 | MMWR (cdc.gov) \n  \n  \n \n  \n   \n     \n   \n \n  \n     \n  \n PCV -experienced adults who completed the recommended \nvaccine series \nShared clinical decision -making is recommended regarding use \nof a supplemental PCV20 or PCV21 dose for adults aged ≥65 \nyears who have completed their recommended vaccine series \nwith both PCV13 and PPSV23. \nRationale: \n▪This adds PCV21 as an option to the current shared clinical decision -making recommendation for \nPCV20 among adults aged ≥65 years who completed the recommended vaccine series with \nPCV13+PPSV23. \n▪Some WG members were in favor of expanding this indication to adults who received all recommended \nvaccine doses with a single dose of PCV20 or PCV15+PPSV23 (especially for adults with risk conditions) \nbut others felt that there was insufficient evidence to support that. \n▪A phase 3 clinical trial on PCV21 use among PCV -experienced children with risk conditions is underway1; \nproposal to discuss PCV21 use in children and adults with risk conditions who completed \n49 recommended \nvaccine series together. \n1. NCT06177912 \n  \n \n \n  \n       PCV -experienced adults who completed the \nrecommended vaccine series \nUnderlying \nconditions \nNone \nChronic \nmedical \nconditions \nCSF leak, \ncochlear \nimplant \nImmuno -\ncompromised Age 19 –64 years \nNo vaccine recommendation Age ≥65 years \n≥8wks* PCV13 PPSV23 ≥1yr \nAND \nPCV21Shared clinical ≥5yrs ORdecision -making \nPCV20 \nPneumococcal Vaccine for Adults Aged ≥19 Years: Recommendations of the Advisory Committee on Immunization Practices, United S tates, 2023 | MMWR (cdc.gov) \n50 \n   \n  \n  \n   \n   \n PCV -experienced adults who have not completed the \nrecommended vaccine series \nA single dose of PCV21 is recommended as an option for adults \naged ≥19 years who have started their pneumococcal vaccine \nseries with PCV13 but have not received all recommended \nPPSV23 doses. \nRationale: \n▪This adds PCV21 as an option to the current recommendation to complete the vaccine series with either \na dose of PCV20 or ≥1 dose of PPSV23. \n▪In addition to those who started the series with PCV13, adults who received PCV15 but have not \ncompleted the series with PPSV23 will have an option to complete the series with either a dose of \nPCV21 or PCV20 if they no longer have access to PPSV23. \n51 \n  \n \n  \n \n      \nPCV -experienced adults who have not completed the \nrecommended vaccine series \nUnderlying \nconditions Age 19 –64 years Age ≥65 years \nNone PCV21 \nOR \nPCV13* ≥1yr PCV20 \nOR \nPPSV23 Chronic \nmedical \nconditions \nCSF leak, \ncochlear \nimplant PCV21 \nPCV13* ≥1yr OR \nPCV20 \nOR \nPCV13 ≥8wks PPSV23 \nOR \nPCV13 ≥8wks PPSV23 ≥5yrs PPSV23 PCV21 \nOR \n≥5yrs PCV20 \nOR \nPPSV23 \n52 Immuno -\ncompromised \n*includes adults who received PCV15 if PPSV23 not available \n \n        \n       \n   \n53 Populations at increased risk of serotype 4 disease \n(draft language) \nIn certain communities where there are high proportions (i.e., \n≥30%) of disease due to serotypes unique to currently \nrecommended vaccines (e.g., serotype 4), those vaccines may \nprovide more protection against locally circulating strains \ncompared to PCV21. Those who may be at increased risk of \ndisease due to serotype 4 include adults aged <65 years in the \nWestern United States with certain underlying conditions or risk \nfactors* that increase the risk of pneumococcal disease. \n*Alcoholism; chronic heart, liver, or lung disease; chronic renal failure; cigarette smoking; cochlear implant; congenital or acquired asplenia; cerebrospinal fluid leak; diabetes \nmellitus; generalized malignancy; HIV; Hodgkin disease; immunodeficiency; iatrogenic immunosuppression; leukemia, lymphoma, o r multiple myeloma; nephrotic syndrome; solid \norgan transplant; sickle cell disease; or other hemoglobinopathies. \n  \n  \n  \n \n \n  Acknowledgments \n▪ACIP and the Pneumococcal Vaccines Work Group \n▪Active Bacterial Core surveillance sites and program \n▪Charles Stoecker, Yin Wang (Tulane University) \n▪Laura Hammitt, Catherine Sutcliffe, Tori Sergent (Johns Hopkins Center for Indigenous \nHealth) \n▪CDC contributors and consultants: Ryan Gierke, Jennifer Farrar, Andrew Leidner, \nKristin Andrejko, Lindsay Zielinski, Emma Accorsi, Wei Xing, Adam Cohen, Alison \nAlbert, Angela Jiles, Noele Nelson, Kimberly Fox, Pedro Moro, Bo -Hyun Cho, Elizabeth \nVelazquez, Janelle King, Fangjun Zhou, Marc Fischer, Laurie Orell, Cheryl Ward, \nRebecca Morgan, Doug Campos -Outcalt \n\n  \n   \n         \n  \n     \n       - - - -\n- - -Thank you \nFor more information, contact CDC \n1 800 CDC INFO (232 4636) \nTTY:  1 888 232 6348 www.cdc.gov \nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention. \nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation \nuse. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.", "summary": "Centers for Disease Control and Prevention  National Center for Immunization and Respiratory Diseases  Summary of Work Group Interpretations of EtR and  Policy Option on PCV21 Use in Adults  June 2024, ACIP Meeting  June 27, 2024  Miwako Kobayashi, MD, MPH, FACP , FIDSA  Photographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation  use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/04-Pneumococcal-Kobayashi-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 55}
{"title": "01 Mening Loehr 508", "content": "Introduction to Session: \nMeningococcal Vaccines\nJamie Loehr, MD\nChair, ACIP Meningococcal/Hib Vaccines Work Group\nJune 28, 2024National Center for Immunization & Respiratory Diseases\n1\nACIP Meningococcal/Hib Vaccines Work Group\n▪ ACIP Members on the WG\n•Jamie Loehr (Chair)\n•Wilbur Chen\n▪ Ex Officio WG Members\n•Margaret Bash (FDA)\n•Matthew Clark (IHS)\n•Xin-Xing Gu (NIH)\n▪ WG Liaisons and Consultants\n•Amra Resic  (AAFP)\n•Mary Healy (AAP) \n•Barb Fluty (ACHA)\n•Karyn Lyons (AIM)\n•Paul Cieslak (CSTE)\n•Kathy Hsu (IDSA)\n•Pamela Doyon -Plourde (NACI)\n•Jeff Goad (NFID)\n•Jessica Cataldi (PIDS)\n•Amy Middleman (SAHM)\n•Kathy Poehling (Wake Forest)\n•Lynn Bahta (Minnesota Department of Health)\n•David Stephens (Emory)\n▪ GRADE/ EtR Support\n•Doug Campos -Outcalt (Arizona)\n•Rebecca Morgan (Case Western Reserve)▪ CDC Contributors\n•Sarah Schillie (DBD/NCIRD)\n•Jennifer Collins (DBD/NCIRD)\n•Lucy McNamara (DBD/NCIRD)\n•LeAnne Fox (DBD/NCIRD)\n•Susan Hariri (DBD/NCIRD)\n•Amy Rubis (DBD/NCIRD)\n•Noele Nelson (DBD/NCIRD)\n•Alison Albert (DBD/NCIRD)\n•Shelby Miller (DBD/NCIRD)\n•Michelle Hughes (DBD/NCIRD)\n•Brian Edwards (DBD/NCIRD)\n•Isha Berry (DBD/NCIRD)\n•Madhura Vachon (DBD/NCIRD)\n•Gabrielle Cooper (DBD/NCIRD)\n•Xiaoyu Dong (ISD/NCIRD)\n•Andrew Leidner (ISD/NCIRD)\n•Ismael Ortega -Sanchez (CORVD/NCIRD)\n•Liz Velazquez (ISD/NCIRD)\n•Marc Fischer (DIDRI/NCEZID)\n•Jonathan Duffy (DHQP/NCEZID)\n•Pedro Moro (DHQP/NCEZID)\n•Tanya Myers (DHQP/NCEZID) \n•Leslie Lee (OD/NCIRD)\n•Manisha (Mo) Patel (OD/NCIRD)\n•Jessica MacNeil (ACIP Secretariat)\n•Hannah Rosenblum (ACIP Secretariat)\n•Melinda Wharton (ACIP Secretariat)\n2\nTwo Terms of Reference\n▪GSK’s MenABCWY  Vaccine\n▪Revisiting the adolescent meningococcal \nvaccine schedule\n3\n4Today’s agenda\nAll topics will be presented for information and discussionTopic Presenter\nEpidemiology Updates Ms. Amy Rubis (CDC/NCIRD)\nGSK Pentavalent Vaccine \nImmunogenicity and SafetyDr. Wendy Sohn (GSK)\nWork Group Considerations Regarding \nMenABCWY  Vaccine and Discussion of \nPotential Risk Groups for MenB  \nVaccinationDr. Sarah Schillie (CDC/NCIRD)\nPolicy Questions for GSK’s MenABCWY  (Pentavalent) Vaccine\n▪Should the pentavalent vaccine be included as an option for MenACWY /MenB  \nvaccination in people currently recommended to receive both vaccines at the same \nvisit?\n•For example, 16 year -olds*\n▪Should the pentavalent vaccine be included as an option for people currently \nrecommended to receive MenACWY  only?\n•For example, 11 –12 year -olds\n▪Should the pentavalent vaccine be included as an option for people currently \nrecommended to receive MenB  only?\n• For example, during a serogroup B outbreak\n*16 year -olds who receive the MenB  vaccine based on shared clinical decision -making 5\nUpcoming ACIP Meetings\n▪October 2024\n•GRADE/ EtR\n•Cost -effectiveness analysis\n▪February 2025\n•Anticipated Vote\n6", "summary": "Introduction to Session:  Meningococcal Vaccines Jamie Loehr, MD Chair, ACIP Meningococcal/Hib Vaccines Work Group June 28, 2024National Center for Immunization & Respiratory Diseases 1 ACIP Meningococcal/Hib Vaccines Work Group ▪ ACIP Members on the WG •Jamie Loehr (Chair) •Wilbur Chen ▪ Ex Officio WG Members •Margaret Bash (FDA) •Matthew Clark (IHS) •Xin-Xing Gu (NIH) ▪ WG Liaisons and Consultants •Amra Resic  (AAFP) •Mary Healy (AAP)  •Barb Fluty (ACHA) •Karyn Lyons (AIM) •Paul Cieslak…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/01-Mening-Loehr-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 6}
{"title": "02 Mening Rubis 508", "content": "Epidemiology of Meningococcal Disease in the \nUnited States\nAmy Rubis, MPH\nAdvisory Committee on Immunization Practices Meeting\nJune 28, 2024National Center for Immunization and Respiratory Diseases\n\n2▪Overall epidemiology of meningococcal disease in the United\nStates\n▪Recent notable epidemiology\n–Serogroup Y meningococcal disease cases\n–OutbreaksAgenda\n3▪Cases reported through National Notifiable Diseases \nSurveillance System (NNDSS)\n▪Additional serogroup, outcome , and clinical characteristics\ncollected nationally through Enhanced Meningococcal Disease\nSurveillance (EMDS)\n–Isolates submitted for whole -genome sequencingMeningococcal Disease Surveillance\n4▪2023 data are still preliminary\n–Serogroup missing for 14% of cases \n–Clinical characteristics not yet complete\n–All available isolates not yet received and tested to confirm \nserogroup and antimicrobial susceptibility Meningococcal  Disease Surveillance Data, 2023\n50.000.200.400.600.801.001.201.40\n1996 2000 2005 2010 2015 2020 2023Incidence per 100,000\nYearMeningococcal Disease Incidence –\nUnited States, 1996 –2023*\nAbbreviations: MenACWY vaccine = quadrivalent (serogroups A, C, W, and Y) meningococcal conjugate vaccine; MenB  vaccine = serogroup B meningococcal vaccine\nSource: 1996 –2023 NNDSS Data. *2023 NNDSS data are preliminary.0.13 cases/100,000 populationMenACWY vaccine1.2 cases/100,000 \npopulation\nMenB  vaccine\n600.020.040.060.080.10.12\n2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023Incidence per 100,000\nYearB C Y W Other\nSource: NNDSS data with additional serogroup data from Active Bacterial Core surveillance (ABCs) and state health departments  \n*2023 data are preliminaryTrends in Meningococcal Disease Incidence by \nSerogroup – United States, 2006 –2023*\n700.020.040.060.080.10.12\n2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023Incidence per 100,000\nYearB C Y W Other\nSource: NNDSS data with additional serogroup data from Active Bacterial Core surveillance (ABCs) and state health departments  \n*2023 data are preliminaryTrends in Meningococcal Disease Incidence by \nSerogroup – United States, 2006 –2023*\n8Serogroup Y Sequence Type 1466\n9Much of the increase is attributable to NmY ST -1466\n▪In many jurisdictions, the increases are primarily due to NmY \nsequence type (ST) 1466 (clonal complex CC174)\n–Susceptible to all treatment and prophylaxis antibiotics\n▪31 cases of this strain detected in 2022; 122 so far in 2023\n–2023 numbers are preliminary and incomplete\n10Characteristics of ST -1466 Cases\n▪Of those with information available:\n–64% (94/148) among Black or African American persons\n–18% (27/153) in people with HIV\n–Majority had clinical presentations other than meningitis\n•62% (76/122) presented with bacteremia \n–4 cases in individuals who received MenACWY vaccine\n•Among 55% with known vaccine history\n•All were people with HIV\n•3 received vaccine >7 years before onset\n•1 received a single dose 3 years before onset\n11Age distribution among NmY ST -1466 cases\n0%5%10%15%20%25%30%35%40%45%\n<1 1-4 5-10 11-15 16-23 24-44 45-64 ≥65Percent of Cases\nAge Group\nST1466\n12Age distribution among NmY ST -1466 cases\n0%5%10%15%20%25%30%35%40%45%\n<1 1-4 5-10 11-15 16-23 24-44 45-64 ≥65Percent of Cases\nAge Group\nST1466 NmY 2015-2019\n13\nNmY ST -1466 cases by state, 2022 –2023\n14Health Alert Network (HAN) Health Advisory\nIncrease in Invasive Serogroup Y Meningococcal Disease in the United States (cdc.gov)\n\n152024 Meningococcal Disease Cases\n▪As of June 11 2024, 251 cases reported for 2024\n–Increase from 164 in 2023\n▪Serogroup missing for 28% of 2024 cases\n–Of those with known serogroup, 103 (57%) are NmY\n16Overall Meningococcal Disease Epidemiology\n17Average Annual Meningococcal Disease Incidence by \nAge Group and Serogroup―United States, 2012 –2021\nSource: NNDSS data with additional serogroup data from ABCs and state health departments0.000.100.200.300.400.500.600.700.800.901.00\n<1 year 1 year 2-4 years 5-10\nyears11-15\nyears16-20\nyears21-25\nyears26-44\nyears45-64\nyears65-84\nyears85+\nyearsIncidence per 100,000\nAge GroupB ACWY Oth/Unk\n18Average Annual Meningococcal Disease Incidence by \nAge Group and Serogroup―United States, 2012 –2021\nSource: NNDSS data with additional serogroup data from ABCs and state health departments0.000.100.200.300.400.500.600.700.800.901.00\n<1 year 1 year 2-4 years 5-10\nyears11-15\nyears16-20\nyears21-25\nyears26-44\nyears45-64\nyears65-84\nyears85+\nyearsIncidence per 100,000\nAge GroupB ACWY Oth/Unk\n19Average Annual Meningococcal Disease Incidence by \nAge Group and Serogroup―United States, 2012 –2021\nSource: NNDSS data with additional serogroup data from ABCs and state health departments0.000.100.200.300.400.500.600.700.800.901.00\n<1 year 1 year 2-4 years 5-10\nyears11-15\nyears16-20\nyears21-25\nyears26-44\nyears45-64\nyears65-84\nyears85+\nyearsIncidence per 100,000\nAge GroupB ACWY Oth/Unk\n20Average Annual Meningococcal Disease Incidence by \nAge Group and Serogroup―United States, 2012 –2021\nSource: NNDSS data with additional serogroup data from ABCs and state health departments0.000.100.200.300.400.500.600.700.800.901.00\n<1 year 1 year 2-4 years 5-10\nyears11-15\nyears16-20\nyears21-25\nyears26-44\nyears45-64\nyears65-84\nyears85+\nyearsIncidence per 100,000\nAge GroupB ACWY Oth/Unk\n21Average Annual Meningococcal Disease Incidence by \nAge Group and Serogroup―United States, 2012 –2021\nSource: NNDSS data with additional serogroup data from ABCs and state health departments0.000.100.200.300.400.500.600.700.800.901.00\n<1 year 1 year 2-4 years 5-10\nyears11-15\nyears16-20\nyears21-25\nyears26-44\nyears45-64\nyears65-84\nyears85+\nyearsIncidence per 100,000\nAge GroupB ACWY Oth/Unk\n22Average Annual Meningococcal Disease Incidence by \nAge Group and Serogroup―United States, 2012 –2021\nSource: NNDSS data with additional serogroup data from ABCs and state health departments0.000.100.200.300.400.500.600.700.800.901.00\n<1 year 1 year 2-4 years 5-10\nyears11-15\nyears16-20\nyears21-25\nyears26-44\nyears45-64\nyears65-84\nyears85+\nyearsIncidence per 100,000\nAge GroupB ACWY Oth/Unk\n23Average Annual Meningococcal Disease Incidence by \nAge Group and Serogroup―United States, 2022 –2023*\nSource: NNDSS data with additional serogroup data from ABCs and state health departments\n*2023 NNDSS data are preliminary.0.000.100.200.300.400.500.600.700.800.901.00\n<1 year 1 year 2-4 years 5-10\nyears11-15\nyears16-20\nyears21-25\nyears26-44\nyears45-64\nyears65-84\nyears85+\nyearsIncidence per 100,000\nAge GroupB ACWY Oth/Unk\n24Average Annual Meningococcal Disease Incidence by \nAge Group and Serogroup―United States, 2022 –2023*\nSource: NNDSS data with additional serogroup data from ABCs and state health departments\n*2023 NNDSS data are preliminary.0.000.100.200.300.400.500.600.700.800.901.00\n<1 year 1 year 2-4 years 5-10\nyears11-15\nyears16-20\nyears21-25\nyears26-44\nyears45-64\nyears65-84\nyears85+\nyearsIncidence per 100,000\nAge GroupB ACWY Oth/Unk\n25Meningococcal Disease Incidence by Race―United \nStates, 2015 –2023*\nSource: NNDSS data with additional serogroup data from ABCs and state health departments. *2023 NNDSS data are preliminary.\nRace is unknown for 5 -12% of cases per year00.050.10.150.20.250.30.35\n2015 2016 2017 2018 2019 2020 2021 2022 2023Incidence per 100,000\nYear\nWhite Black or African American American Indian or Alaska Native Asian or Pacific Islander\n26Meningococcal Disease Incidence by Race―United \nStates, 2015 –2023*\nSource: NNDSS data with additional serogroup data from ABCs and state health departments. *2023 NNDSS data are preliminary.\nRace is unknown for 5 -12% of cases per year00.050.10.150.20.250.30.35\n2015 2016 2017 2018 2019 2020 2021 2022 2023Incidence per 100,000\nYear\nWhite Black or African American American Indian or Alaska Native Asian or Pacific Islander\n27Average Annual Meningococcal Disease Incidence by Race \namong 11 –20 year olds―United States, 2015 –2023*\nSource: NNDSS data with additional serogroup data from ABCs and state health departments. *2023 NNDSS data are preliminary.\nRace is unknown for 6 -15% of cases per year00.010.020.030.040.050.060.070.080.090.1\nWhite Black or African\nAmericanAmerican Indian or\nAlaska NativeAsian or Pacific\nIslanderIncidence per 100,000\n28Meningococcal Disease Incidence by Ethnicity―United \nStates, 2015 –2023*\nSource: NNDSS data with additional serogroup data from ABCs and state health departments. *2023 NNDSS data are preliminary.\nEthnicity is unknown for 2 -16% of cases per year00.020.040.060.080.10.120.140.16\n2015 2016 2017 2018 2019 2020 2021 2022 2023Incidence per 100,000\nYear\nHispanic or Latino Not Hispanic or Latino\n29Average Annual Meningococcal Disease Incidence by Ethnicity \namong 11 –20 year olds―United States, 2015 –2023*\nSource: NNDSS data with additional serogroup data from ABCs and state health departments. *2023 NNDSS data are preliminary.\nEthnicity is unknown for 3 -27% of cases per year00.010.020.030.040.050.060.070.080.09\nHispanic or Latino Not Hispanic or LatinoIncidence per 100,000\n30Antibiotic -resistant Neisseria meningitidis\n31Antibiotic -resistant N. meningitidis\n▪Penicillin -resistant and ciprofloxacin - and penicillin -resistant \ncases\n–ST-3587\n–Predominately among Hispanic or Latino individuals\n▪Ciprofloxacin -resistant only cases\n32\n00.050.10.150.20.250.3\n05101520253035404550\n2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024\nIncidence per 100,000 populationNumber of cases\nCiprofloxacin-resistant Penicillin-resistant Dual-resistant Meningococcal Disease IncidenceN. meningitidis isolates with penicillin or ciprofloxacin\nresistance Data are not final, and \nnumbers may increase\n33\nResistant N. meningitidis, 2018 –2024\nGeographic \nclusters\nPenicillin -resistant\nCiprofloxacin -resistant\nDual -resistant\nNote:  3 dual -resistant cases missing county of residence/occurrence are excluded from the map\n34Antibiotic -resistant N. meningitidis , 2018 –2024\nDual -resistantPenicillin -resistant \nonlyCiprofloxacin -\nresistant only\nTotal cases (2018 -2024) 72 73 20\nMedian age (range) 39 (0 -97) 50 (0 -89) 45 (3 -84)\n% of cases among Hispanic \nindividuals74% (53/72) 53% (39/73) 10% (2/20)\n% fatal 7% (5/72) 6% (4/73) 0%\n35Antibiotic -resistant N. meningitidis , 2018 –2024\nDual -resistantPenicillin -\nresistant onlyCiprofloxacin -\nresistant only\nAll Serogroups 72 73 20\nNmY or NG with NmY backbone 68/72 73/73 2/20\nNmB 2/72 -- 7/20\nNmC  or NG with NmC  backbone -- -- 3/20\nNmW 1/72 2/20\nNmNG -- -- 6/20\nNot Sequenced Yet 1/69 --\n36Travel history of antibiotic -resistant cases since 2018*\nDual -resistantPenicillin -resistant \nonlyCiprofloxacin -\nresistant only\nTotal 72 73 20\nTravel History 11/72 9/73 3/20\nDomestic 6/11 3/9\nInternational 5/11 6/9 3/3\n    Mexico 2/5 6/6 --\n    Dominican Republic 1/5 -- --\n    Honduras 1/5\n    Kingdom of Saudi Arabia -- -- 3/3\n*One additional dual -resistant case reported in an El Salvador resident and two beta -lactamase \npositive cases reported in Mexico residents who were in the United States at the time of onset\n37Dual -resistantPenicillin -resistant \nonlyCiprofloxacin -\nresistant only\nTotal 72 73 20\nTravel History 11/72 9/73 20\nDomestic 6/11 3/9\nInternational 5/11 6/9 3\n    Mexico 2/5 6/6 --\n    Dominican Republic 1/5 -- --\n    Honduras 1/5\n    Kingdom of Saudi Arabia -- -- 3\n*One additional dual -resistant case reported in an El Salvador resident and two beta -lactamase \npositive cases reported in Mexico residents who were in the United States at the time of onsetTravel history of antibiotic -resistant cases since 2018*\n38\n\n39\nCounties Not Using Ciprofloxacin for Prophylaxis\nFall 2022 PresentTiming of Guidance Implementation\n\n40Outbreaks\n41Meningococcal Disease Outbreaks 2022 -Present\nOutbreak Outbreak  Period Serogroup Cases (deaths)\nFlorida MSM December 2021 – February 2023 C 46 (9)\nNew York PEH February 2022 C 3\nFlorida College February – March 2022 B 3\nVirginia Statewide June 2022 – Present Y 36 (8)*\nIowa Community November 2022 – July 2023 W 12 (2)\nOhio Amish Community December 2023 – January 2024 B 6†\nColorado PEH Jan 2024 – Present Y 6*\nOklahoma Correctional Facility March 2024 – May 2024 C 2 (1)\nKingdom of Saudi Arabia Travel April 2024 – Present W§ 14*\nAbbreviation: MSM, men who have sex with men; PEH, people experiencing homelessness\n*Ongoing\n†5 additional suspect cases\n§One additional serogroup C case and one additional nongroupable case\n42Recent Meningococcal Disease Outbreaks\n*The outbreak is ongoing. Case counts may change.▪Ongoing Statewide NmY ST -1466 Outbreak in Virginia\n–June 2022 –present*\n–36 cases, 7 deaths (19% CFR)\n–28/36 cases in Black or African American persons\n–Age range 16 -82 years, median 47\n43Recent Meningococcal Disease Outbreaks\n▪Amish community outbreak\n–6 confirmed serogroup B cases\n–5 additional suspected cases\n–Age range 1 -10 years\n▪Response measures\n–Mass prophylaxis with ciprofloxacin\n•83% coverage achieved but not all at once\n•One additional case occurred ~1 month after prophylaxis\n–Bexsero recommended for all community members aged 8 weeks and older\n•First time MenB  vaccine has been recommended for people <10 years of age in the \nUnited States\n•Recommendation based on extensive safety data in infants in UK and elsewhere\n•94% coverage achieved with first dose\n•56% coverage achieved with second dose\n44Recent Meningococcal Disease Outbreaks\n▪People experiencing homelessness in Colorado*\n–6 serogroup Y cases\n–Age range 5 months -76 years\n–Penicillin -resistant ST -3587 strain\n•Not ciprofloxacin -resistant\n•Different population from the one primarily affected by the strain\n*The outbreak is ongoing. Case counts may change.\n45Recent Meningococcal Disease Outbreaks\n▪People with travel to the Kingdom of Saudi Arabia (KSA)*\n–14 total cases in 4 countries: United States (6), France (4), \nUnited Kingdom (3)​, Norway (1)\n•10 cases in adults with travel history to KSA, 4 cases in children who \nwere close contacts of traveler​s\n–12 serogroup W, 1 serogroup C, 1 nongroupable​\n–All travelers participated in Umrah​\n–No travelers known to be vaccinated\n–4 cases (2 NmW , 1 NmC , 1 NmNG ) resistant to ciprofloxacin​\n*The outbreak is ongoing. Case counts may change.\n46\n▪Recommend \npreferential use of \nalternative prophylaxis \nagents for cases \nassociated with KSA \ntravel\n47Conclusions\n▪Incidence of meningococcal disease increased in 2023, \nprimarily due to NmY ST -1466\n–ST-1466 primarily observed among those aged 30 -60 years\n▪Ciprofloxacin resistance is increasing\n–Multiple jurisdictions have discontinued ciprofloxacin use\n–Increasing number of resistant isolates not serogroup Y\n48Conclusions\n▪New strains emerging in the United States\n–Predominantly affecting racial minority groups leading to an \nincreasing disparity in incidence among Black persons \ncompared to other racial groups\n▪Large number of outbreaks since 2022\n–Affecting minorities or disadvantaged populations\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position \nof the Centers for Disease Control and Prevention.\nThank you\n50Backup slides\n51No confirmed instances of \nprophylaxis failure with \nciprofloxacin reported to date… \nbut concerning anecdotes", "summary": "Epidemiology of Meningococcal Disease in the  United States Amy Rubis, MPH Advisory Committee on Immunization Practices Meeting June 28, 2024National Center for Immunization and Respiratory Diseases  2▪Overall epidemiology of meningococcal disease in the United States ▪Recent notable epidemiology –Serogroup Y meningococcal disease cases –OutbreaksAgenda 3▪Cases reported through National Notifiable Diseases  Surveillance System (NNDSS) ▪Additional serogroup, outcome , and clinical…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/02-Mening-Rubis-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 51}
{"title": "03 Mening GSK 508", "content": "MenABCWY for the prevention of \nInvasive Meningococcal Disease \ncaused by serogroups A, B, C, W and Y\nWendy Sohn, MD\nGlobal Medical Lead Neisseria Vaccines\n2\nPresentation by GSK at ACIP, June 2024\nConcerted Prevention of IMD in Adolescents and Young Adults\nImprove vaccination \ncoverage  rates5 to meet the \ngreatest medical needReduce overall burden \nof pain and discomfort6\nImproved convenience and \ncompliance6Potentially better  overall \neconomic value6Need for \npentavalent \nvaccines\n1.Mbaeyi S, et al. JAMA Pediatr 2020; 174 (9):843- 851; 2. Enhanced Meningococcal Disease Surveillance Reports 2015- 2022; 3. CDC Immunization Schedule 2024; 4. Pingali  C, et al. MMWR Morb  Mortal Wkly Rep 2023; 72(34):912- 919; 5. Marshall G, et al . Clin Infect Dis 2022, \n75(1):155- 158; 6. Kroger A, et al. General  Best Practice Guidelines for Immunization. [www.cdc.gov/vaccines/hcp/acip -recs/general -recs/downloads/general -recs.pdf]. Accessed on February 28th, 2024.IMD is an uncommon but \npotentially devastating \ndisease1Out of 5 serogroups : B (75%), \nCWY(25%) in 16 -23-year-olds2Recommendations based on \nage and high- risk conditions3\nLow vaccination coverage \nfor those at high- risk and \npersistent disparities4,5\n\n3\nPresentation by GSK at ACIP, June 2024Immunogenicity in high- risk \npatients7,8Immunogenicity and Safety in \nHealthy 2 months -55 year -olds2 MenABCWY Program Built on Antigenic Components of \nMenACWYCRM (Menveo) and MenB -4C (Bexsero)\nReal- world effectiveness13Persistence of immune response \nafter 4 -7.5 years12Immunogenicity and Safety in \nHealthy 10- 25 year -olds3\nReal- world effectiveness14-16Immunogenicity in high- risk \npatients4-6\nPersistence of immune response \nafter 4 -6 years9-11Immunogenicity and Safety in \nHealthy 10-25 year -oldsMenACWYCRM2MenB -4C3\n2010 2015 Anticipated 20251MenABCWY1=Lyophilized MenACWYCRM\n(vial)+\n1. GSK Press Release  April 16, 2024. https://www.gsk.com/en -gb/media/press -releases/gsk -s-5-in-1-meningococcal -abcwy -vaccine -candidate- accepted -for-regulatory -review -by-us-fda/; 2. Prescribing Information for MENVEO ; 3. Prescribing Information for BEXSERO ; 4. Isitt C et al, HIV \nMed. 2023; 24(9):979- 989; 5 . Kimura A et al, Clinical and Vaccine Immunology . 2011; 18(3):483- 486;  6. Findlow  J et al, Vaccine.  2015; 33(29):3322- 30; 7.Martinon -Torres F et al, P ediatrics . 2018; 142(3): e207174250; 8. Robin C et al , Clin Microbiol  Infect. 2022, 28(12):1609- 1614; 9. \nTipton et al, Vaccine.  2019; 37(42):6171- 6179; 10. Baxter et al, Pediatr  Infect Dis J. 2014; 33(11):1169 -1176; 11. Jacobson et al Pediatr  Infect Dis J. 2013; 32(4):e170- 177; 12. Watson PS et al. Expert Review of Vaccines.  2019; 18:4, 343- 352; 13. Hyoung Im J et al, Vaccine.  2020; 38 \n(730- 732); 14. McMillan M et al, Clin Infect Dis.  2021; 73(1):e233– 7; 15. Wang B et al Lancet Infect Dis.  2022; 22:1011– 20; 16. Wang B et al. J Infect. 2023; 22:S0163– 4453Liquid MenB -4C\n(prefilled syringe)\n4\nPresentation by GSK at ACIP, June 20241. GSK Press Release  April 16, 2024. https://www.gsk.com/en -gb/media/press -releases/gsk -s-5-in-1-meningococcal -abcwy -vaccine- candidate- accepted- for-regulatory -review -by-us-fda/; \n2. MenABCWY Candidate Vaccine Draft Prescribing Information, February 2024\nVaccine indicated for active immunization to prevent invasive disease \ncaused by Neisseria meningitidis serogroups A, B, C, W, and Y in \nindividuals 10 through 25 years of age\nAdminister 2 doses (0.5 mL each) intramuscularly at least 6 months apart MenABCWY Proposed Indication2MenABCWY Program Built on Antigenic Components of \nMenACWYCRM (Menveo) and MenB -4C (Bexsero)\nMenABCWY1=Lyophilized MenACWYCRM\n(vial)+Liquid MenB -4C\n(prefilled syringe)\n5\nPresentation by GSK at ACIP, June 2024\nVaccine exposed set1N\nMenABCWY (Total) 3,718 \n MenABCWY  1,216\nMenB -4C 2,969\nMenACWYCRM 361\nTOTAL \nreceiving ≥ 1 dose of study vaccine7,048Comprehensive MenABCWY Clinical Development Program\n12 Studies, >7,000 Participants, 13 Countries\n10 completed Ph1-2 studies: different formulations and administration schedules in ages 9 –  42 years1  \n2 completed Ph3 studies: safety and immunogenicity of MenABCWY in MenACWY -naïve and primed 10-\n25 yrs2-3\n1 ongoing Phase 2 study: evaluating 2 doses administered 2 or 4 years apart in ages 11 –  14 years4\nNorth America\nN=2,770\nSouth America \nN=447\nAustralia\nN=532\nEurope\nN=3,299\n1. GSK, Data on File 2024N555071; 2. Clinicaltrials.gov identifier NCT04502693 , accessed May 31st, 2024; 3. Clinicaltrials.gov identifier  NCT04707391 , accessed May 31st, 2024; 4. Clinicaltrials.gov identifier NCT05087056 , accessed May 31st, 2024.\n6\nPresentation by GSK at ACIP, June 2024\n10-25 years of age\nMenACWY -naïve\n15-25 years of age\nMenACWY -primed*\nMenABCWY -019Phase 3 Studies Assessed Safety and Immunogenicity of MenABCWY\nMenB-4C 0,2,6\nN=897\nMenB-4C 0,6\nN=906\nMenACWYCRM \nN=178\nMenABCWY 0,6\nN=1,657\nN=1,247\nMenACWYCRM  + \nMenB N=621\nMenABCWY 0,6\nN=626\nMonth 0 1 2 3 6 7 12\n V72_72\nN for each study arm depicts the exposed set. *MenACWY -primed participants received dose of licensed MenACWY vaccine ≥ 4 years prior to study start \nClinicaltrials.gov identifier NCT04502693 , accessed May 31st, 2024 and Clinicaltrials.gov identifier  NCT04707391 , accessed May 31st, 2024.Compared to MenB- 4C, MenACWYCRM Administered per CDC Schedule at Study Onset\nStudy populations\nHealthy participants, \nwithout progressive, \nunstable or \nuncontrolled clinical \nconditions (including \nabnormal immune \nfunction)\nMenB -naïveN=3,638\nPlacebo MenABCWY MenB -4C MenACWYCRM\n7\nPresentation by GSK at ACIP, June 2024Demographics and Baseline Characteristics of Phase 3 Studies\nV72_72 MenABCWY -019\nMenABCWY\nN=1,657MenB -4C 0- 6\nN=906MenACWYCRM\nN=178MenABCWY\nN=626MenACWYCRM\nN=621\nMedian age At 1st vaccination, years (range) 16 (9 –26) 16 (9 –26) 16 (10 –25) 16 (15 –25) 16 (15 –25)\nAge group10–11 years 320 (19%) 172 (19%) 27 (15%) 0 0\n12–17 years 666 (40%) 368 (41%) 76 (43%) 450 (72%) 441 (71%)\n18–25 years 671 (40%) 366 (40%) 75 (42%) 176 (28%) 180 (29%)\nRegion US 491 (30%) 270 (30%) 52 (29%) 366 (59%) 365 (59%)\nSex Female 933 (56%) 446 (49%) 100 (56%) 343 (55%) 325 (52%)\nRaceWhite 1492 (90%) 791 (87%) 162 (91%) 474 (76%) 467 (75%)\nAsian 71 (4%) 60 (7%) 9 (5%) 22 (4%) 33 (5%)\nBlack or African American 59 (4%) 29 (3%) 6 (3%) 94 (15%) 86 (14%)\nOther 35 (2%) 26 (3%) 1 (1%) 36 (6%) 38 (6%)\nEthnicityNot Hispanic or Latino 1546 (93%) 852 (94%) 172 (97%) 447 (71%) 432 (69%)\nHispanic or Latino 92 (6%) 41 (5%) 6 (3%) 179 (29%) 192 (31%)\nNot reported 19 (1%) 13 (1%) 0 0 0\nN for each study arm depicts the exposed set.\nClinicaltrials.gov identifier NCT04502693 , accessed May 31st, 2024 and Clinicaltrials.gov identifier  NCT04707391 , accessed May 31st, 2024.\n\n8\nPresentation by GSK at ACIP, June 2024Immunogenicity of MenABCWY against \n110 serogroup B strains \nGSK’s \nMenABCWYSerogroup B Serogroups A C W Y\nImmunological noninferiority \nofMenABCWY vs MenB -4C\nPersistence and booster immune \nresponse up to 24 months \nEvidence Supporting Safety and Immunogenicity of MenABCWY  \nSolicited and unsolicited adverse events after each dose of MenABCWY, MenB -4C or MenACWYCRM\nNon- inferiority vs MenACWYCRM \nin MenACWY -naïve and -primed\nClinicaltrials.gov identifier NCT04502693 , accessed May 31st, 2024; Clinicaltrials.gov identifier  NCT04707391 , accessed May 31st, 2024; Vesikari T et al. Hum Vaccin Immunother 2021;17(11):4689- 4700\n9\nPresentation by GSK at ACIP, June 20240%20%40%60%80%100%\n†Severity of symptom‡Size (mm)‡Fever ( °C)\nMild –easily tolerated 25–50 38.0– 38.9\nModerate –interferes with normal activity 51–100 39.0– 39.9 \nSevere –prevents normal activity >100 ≥ 40.0MenABCWY \n0-6m\nMenB -4C \n0-2m\nMenACWYCRM\n(1 dose)\nAE: adverse event; *Number of participants varies by study vaccination: 1428- 1638 for MenABCWY arm, 823- 835 for MenB -4C and 178 for MenACWY.  \nGSK, Data on File 2024N555060\n Generally  mild-to-moderate , with mean duration of 1 -4 days, depending on AE\n Occurred at similar rates after MenABCWY and MenB -4C, and higher than after MenACWYCRM\n No observed difference between 1st and 2nd dose MenABCWYInjection-\nsite pain†Swelling‡Induration‡Erythema‡Fatigue†Headache†Myalgia†Arthralgia†Nausea†Fever‡\n1 2 1 2 1 2 1 2 1 2 1 2 1 2 1 2 1 2 1 2Solicited Local AEs Solicited Systemic AEsParticipants*\nDose \nPhase 3: V72_72Solicited Local and Systemic AEs within 7 Days, after Each \nVaccination with MenABCWY, MenB- 4C or MenACWYCRM\n10\nPresentation by GSK at ACIP, June 2024MenABCWY  Demonstrated a Well -Tolerated Safety Profile \nComparable to MenB- 4C\nIntegrated Safety Analysis (Pooled) \nN =7,048MenABCWY\nN=3,718MenB -4C\nN=2,969MenACWYCRM     \nN=361\nn (%) n (%) n (%)\nUnsolicited AEs (within 30 days of any vaccination) 1,072 (29%) 736 (25%) 47 (13%)\nRelated* 256 (7%) 155 (6%) 10 (3%)\nAEs leading to withdrawal 8 (0.2%) 4 (0.1%) 0\nMedically attended AEs† 416 (12%) 302 (11%) 8 (4%)\nRelated medically attended AEs† 22 (0.6%) 15 (0.5%) 0\nSAEs (entire study period) 70 (1.9%) 58 (2%) 5 (1.4%)\nRelated* 3 (0.1%) 2‡ (0.1%) 0\nDeaths (all unrelated) 1§2¶1§\n*Assigned as related by investigator; † Medically attended flags for AEs are not available in studies V102P1, V102_02, V102_02E1 and V102_03. Participants from these studies are not included. Therefore, the denominator \nis different for the 3 groups (MenABCWY N=3488, MenB N=2861, MenACWY N=213); ‡ 2 SAEs occurred in the MenB -4C arms of the studies included in the pooled safety analysis: 1 SAE followed a MenB -4C and 1 \nfollowed a MenACWY -CRM vaccination;  §Suicide; ¶ Deaths by poisoning and drug overdose; AE: adverse event; SAE: serious adverse event \nGSK, Data on File 2024N555058.\n11\nPresentation by GSK at ACIP, June 2024Serogroup B Serogroups A C W YEvidence Supporting Safety and Immunogenicity of MenABCWY \nSolicited and unsolicited adverse events after each dose of MenABCWY, MenB -4C or MenACWYCRM\nImmunogenicity of MenABCWY against \n110 serogroup B strains \nGSK’s \nMenABCWYImmunological noninferiority \nofMenABCWY vs MenB -4C\nPersistence and booster immune \nresponse up to 24 months \nSolicited and unsolicited adverse events after each dose of MenABCWY, MenB -4C or MenACWYCRM\nNon- inferiority vs MenACWYCRM \nin MenACWY -naïve and -primed\nClinicaltrials.gov identifier NCT04502693 , accessed May 31st, 2024; Clinicaltrials.gov identifier  NCT04707391 , accessed May 31st, 2024; Vesikari T et al. Hum Vaccin Immunother .2021;17(11):4689 -4700\n12\nPresentation by GSK at ACIP, June 2024Assays Used to Infer Meningococcal Vaccine Protection\nhSBA, human serum bactericidal assay\n1. CDC, 2022. About meningococcal vaccines. https://www.cdc.gov/vaccines/vpd/mening/hcp/about -vaccine.html ; 2. Donald RGK et al. Hum Vaccin Immunother .2017;13:255– 265; 3. Balmer P et al. Postgrad Med. 2020;132:184– 191; \n4. Goldschneider I, et al. J Exp Med. 1969;129(6):1307 -1348; 5. Bröker M et al. Vaccine. 2009;27:5574– 5580; 6.Ferlito et al. Clin Exp Immunol . 2018;194(3): 361- 370; 6. Muzzi A et al. MSphere. 2022;e00385223\nN. meningitidis \ncapsule polysaccharideMenACWY  \nVaccines\nhSBA against serogroup-\nspecific polysaccharide \ncapsule reference strain \ninfers protection against all \nstrains in serogroup2Vaccine targets Traditional hSBA\nHighly abundant, \nconserved \nantigens1\nSurrogate of protection: \ntiter ≥4 threshold for \nprotection2,3,4,5,6\n13\nPresentation by GSK at ACIP, June 202497.0 97.2 97.0 96.7\n85.7\n50.061.769.7\n0%20%40%60%80%100%MenABCWY  Non-Inferior to MenACWYCRM in MenACWY -Naïve and \nMenACWY -Primed Participants\n% with 4 -fold Rise \nin hSBA Titers*†\n(95% CI)\n*At 1 month after 1 or 2 doses of MenABCWY or after single MenACWY vaccination; †Defined as a post -vaccination titer ≥4- fold the LOD or ≥LLOQ, whichever is greater if pre-vaccination titer <LOD, a post -vaccina tiontiter ≥4 -fold the LLOQ if pre- vaccination titer ≥LOD and <LLOQ, and \na post -vaccination titer ≥4- fold the pre- vaccination titer if pre -vaccination titer ≥LLOQ. LOD: 4 for MenA, MenC, MenW, and MenY. LLOQ =12 for MenA; 8 for MenC; 8 for MenW; 10 for MenY, except for the post -hoc analysis  for which LLOQs were 8 for MenA and 11 for MenC; \n‡Licensure criteria agreed with CBER; # full set analysis; **Primed participants had received a dose of MenACWY vaccine at least 4 years prior. CI –confidence interval, hSBA - human serum bactericidal assay, LOD – limit of detection; LLOQ – lower limit of quantitation \n1. Clinicaltrials.gov identifier NCT04502693 , accessed May 31st, 2024; 2.  Clinicaltrials.gov identifier  NCT04707391 , accessed May 31st, 2024; 3. GSK, Data on File 2024N555056.75.2\n64.572.6 74.885.1\n50.962.470.2\n0%20%40%60%80%100%\nV72_72: \nMenACWY -Naïve1 dose MenABCWY compared to 1 dose \nMenACWYCRM#,3\n95.2 94.4 95.6 95.0 95 94 93.9 94.4\n0%20%40%60%80%100%\nMenABCWY -019: \nMenACWY -Primed**% with 4 -fold Rise \nin hSBA Titers*†\n(95% CI)\nW Y A C\nW Y A CSUCCESS CRITERION MET : LL of 95% CI > -10% 92.5 94.0 94.3 93.7 95 94 93.9 94.4\n0%20%40%60%80%100%\nSUCCESS CRITERION MET : LL of 95% CI > -10% Post hoc analysis\n2 doses MenABCWY non-inferior \nto 1 dose MenACWYCRM‡,21 dose MenABCWY non-inferior to 1 dose \nMenACWYCRM2MenABCWY \n(2 doses) \nMenACWY\n(1 dose)MenABCWY\n(1stdose) W Y A C\nW Y A CN=113 N=114 N=124 N=116 N=124 N=117 N=131 N=121 N=1,170 N=112 N=1,189 N=114 N=1,185 N=115 N=1,196 N=1192 doses MenABCWY non-inferior \nto 1 dose MenACWYCRM‡,1\nN=168 N=505 N=180 N=546 N=180 N=544 N=179 N=537 N=509 N=505 N=570 N=546 N=565 N=544 N=567 N=537SUCCESS CRITERION MET : LL of 95% CI > -10% \n14\nPresentation by GSK at ACIP, June 2024\nGSK developed enc-hSBA5to \ntest against multiple serogroup B \nstrains\n110 strains randomly selected \nfrom 2000-2008 IMD cases, that continue to represent 95% of US \ndisease causing serogroup B strains\n5collected up to 2017Assays Used to Infer Meningococcal Vaccine Protection\nhSBA, human serum bactericidal activity; enc -hSBA, endogenous complements human serum bactericidal activity, Men, meningococcal serogroup; fHbp – factor H binding protein; NHBA – Neisserial Heparin Binding \nAntigen; NadA – Neisseria Adhesin A; PorA1 P1.4 –  porin A1 P1.4. *A MenB capsular vaccine was poorly immunogenic due to structural similarity between the capsule and human tissue5\n1.CDC, 2022. About meningococcal vaccines. https://www.cdc.gov/vaccines/vpd/mening/hcp/about -vaccine.html ; 2. Donald RGK et al. Hum Vaccin Immunother .2017;13:255– 265; 3. Balmer P et al. Postgrad \nMed.2020;132:184– 191; 4. Kleinschmidt A et al. NPJ Vaccines .2021;6:29; 5. Muzzi A et al. MSphere. 2022;e00385223\nN. meningitidis \ncapsule polysaccharideMenACWY  \nVaccines\nN. meningitidis \nsubcapsular* proteins\nhSBA against serogroup-\nspecific polysaccharide \ncapsule reference strain \ninfers protection against all \nstrains in serogroup2\nhSBA does not assess \nvaccine induced immune \nresponse against many \ndiverse strains expressing \nmore than 1 antigen4\nVaccine targetsMenB  \nVaccinesfHbp\nNHBA\nPorA1 \nP1.4\nNadATraditional hSBA\nHighly abundant, \nconserved antigens1\nVariable \nexpression among \ndisease-causing\nserogroup B \nstrains3\nenc-hSBA\n15\nPresentation by GSK at ACIP, June 2024enc-hSBA: Immune Response Against Diverse Serogroup B \nStrains in MenABCWY  vs MenB -4C Arms\nImmunological Vaccine Effectiveness (IVE)\n*relative risk = ratio between % of tests lacking bactericidal activity against 110- strain panel in group receiving MenB -containi ng vaccine and control (MenACWY vaccine); †Target number of strains tested for each participant \nwas 35 strains out of the 110 strains panel . MenB: meningococcal serogroup B; enc-hSBA: endogenous complement serum bactericidal activity; IVE: immunological vaccine effectiveness\nWelsch et al, Vaccine.  2018;36(15): 5309- 5317; Clinicaltrials.gov identifier NCT04502693 , accessed May 31st, 2024Percentage of participants whose \nsera killed ≥70% of strains tested†\ninforms on breadth of MenB vaccine strain \ncoverage at a population level percentage of participants achieving broad \nprotection against serogroup B strainsTest-Based Responder -Based\nIVE = (1 – relative risk) x 100\nRelative risk defined as the percentage of tests \nwithout bactericidal activity inthe group \nreceiving MenB -containing vaccine compared to \ncontrols\n16\nPresentation by GSK at ACIP, June 2024enc-hSBA: Immune Response against Diverse Serogroup B \nStrains after 2 doses of MenABCWY or MenB- 4C\nThe 3 MenB -4C schedules were hierarchically tested for IVE in the order: MenB -4C 0- 2-6m  MenB -4C 0- 6mMenB -4C 0- 2m. The 0- 2m schedule was the last schedule to meet the predefined success criterion ( LL of 95% CI > 65%) and \nwas hence chosen as the comparator for the MenABCWY  0-6m schedule for all subsequent statistical analyses. LL, lower limit; IVE: immunological vaccine effectiveness\nClinicaltrials.gov identifier NCT04502693 , accessed May 31st, 2024\nMenABCWY achieved breadth of bactericidal effect against a diverse and broad panel of serogroup B \nstrains, similar to MenB -4C 2-dose  administered 2 or 6 months apart0%20%40%60%80%100%81.8\n(80.4– 83.1)78.7\n(77.2– 80.1)\nvs MenACWYCRM control (4374 tests)MenB -4C 0,6m\n(26,142 tests)MenB -4C 0,2m\n(27,569 tests)MenABCWY 0,6m\n(25,715 tests)77.9\n(76.6– 79.2)\n0%20%40%60%80%100%89.8\n(87.2– 92.0)84.8\n(81.8– 87.5)\nMenB -4C0,6m\n(813 participants)MenB -4C0,2m\n(831 participants)MenABCWY 0,6m\n(817 participants)84.1\n(81.4– 86.5)\nSUCCESS \nCRITERION MET:\nLL of 97.5% CI > 65% Test-Based IVE Responder -Based IVE\nInforms breadth of MenB vaccine strain \ncoverage at a population level % participants achieving broad protection \nagainst serogroup B strains\n17\nPresentation by GSK at ACIP, June 2024\nMenABCWY  was noninferior to MenB -4C, based on bactericidal effects against diverse strains \nassessed by enc-hSBA  assay\n*The 3 MenB -4C schedules were hierarchically tested for IVE in the order: MenB -4C 0- 2-6m  MenB -4C 0- 6mMenB -4C 0- 2m. The 0- 2m schedule was the last schedule to meet the predefined success criterion ( LL of 97.5% \nCI > 65%) and was hence chosen as the comparator for the MenABCWY 0- 6m schedule for all subsequent statistical analyses. LL, lower limit\nClinicaltrials.gov identifier NCT04502693 , accessed May 31st, 2024enc-hSBA: Noninferiority of Immune Response against Diverse \nSerogroup B Strains in MenABCWY  vs MenB- 4C\n0%20%40%60%80%100%\nMenABCWY\n(25,715 tests)MenB -4C 0,2m\n(27,569 tests)-0.61\n(-1.25 to 0.03)\nSUCCESS CRITERION MET:\nLL of 95% CI > - 5% \n82.5%\n(82.1- 83)85.6%\n(85.1- 86)\n% of Samples with\nBactericidal Serum\nActivity\n(95% CI)\nMenB -4C 0,6m\n(26,142 tests)83.1%\n(82.7- 83.6)-3.02\n(-3.65  to -2.39 )\n18\nPresentation by GSK at ACIP, June 202478.992.3\n61.1\n42.482.495.3\n69.5\n57.2\n0%20%40%60%80%100%\nN=693 N=729 N=699 N=725 N=700 N=731 N=704 N=664*\nNHBA PorA P1.4 fHbp NadA% with 4 -fold Rise in hSBA Titers*\n(95% CI)79.792.7\n61.9\n42.274.796.4\n58.653.3\n0%20%40%60%80%100%\nNHBA PorA P1.4 fHbp NadA\nMenABCWY 0,6m MenB -4C 0,2mN=675 N=719 N=671 N=717 N=678 N=718 N=642 N=704Group difference: \n(95%CI)-3.53​\n(-7.6to 0.6)​–3.01\n(–5.6to –0.5)​-8.31\n(–13.2 to -3.4)​–14.80\n(–20.0 to –9.5)Group difference: (95%CI)5.02\n(0.6 to 9.4)​–3.68\n(–6.2to –1.3)​3.31\n(–1.8to 8.4)​–11.06\n(–16.3 to –5.7)\nMenABCWY 0,6m MenB -4C 0,6m\nSUCCESS CRITERION:\nLL of 95% CI > - 10% \n% with 4 -fold Rise in hSBA Titers*\n(95% CI)hSBA : MenABCWY Immune Response Against Serogroup B \nReference Strains\nSecondary endpoint not met because success criterion not met for all 4 strains \nMenABCWY elicited comparable immune responses for 3 reference strains vs MenB -4C 0,2 and 2 reference strains vs \nMenB -4C 0,6m. MenABCWY 0,6m vs MenB -4C 0,2 m MenABCWY 0,6m vs MenB -4C 0,6 m\n*At 1 month after 2nd MenABCWY or 2nd  MenB -4C vaccination, relative to baseline. 4- fold rise in hSBA titer for each strain was defined as a post -vaccination titer ≥ 4-fold the LOD or ≥LLOQ, whichever is greater if pre-vaccination titer <LOD, a post -vaccination titer ≥4 -fold the LLOQ if pre-\nvaccination titer ≥LOD and <LLOQ, and a post -vaccination titer ≥4- fold the pre- vaccination titer if pre -vaccination titer ≥LLOQ. LOD – limit of detection; LLOQ – lower limit of quantitation; LOD: fHbp: 3; NadA: 6; NHBA: 4; PorA P1.4: 4. LLOQ: fHbp: 5; NadA : 15; NHBA: 4; PorA P1.4: 6.  fHbp, \nfactor H binding protein; hSBA, human serum bactericidal assay; LL, lower limit; LOD – limit of detection; LLOQ – lower limit of quantitation; NadA, Neisseria  adhesin A; NHBA, Neisserial heparin- binding antigen; Por A P1.4, porin A\nClinicaltrials.gov identifier NCT04502693 , accessed May 31st, 2024\n19\nPresentation by GSK at ACIP, June 2024Serogroup B Serogroups A C W Y\nSolicited and unsolicited adverse events after each dose of MenABCWY, MenB -4C or MenACWYCRM\nImmunogenicity of MenABCWY against \n110 serogroup B strains \nGSK’s \nMenABCWYImmunological noninferiority \nofMenABCWY vs MenB -4C\nPersistence and booster immune \nresponse up to 24 months \nSolicited and unsolicited adverse events after each dose of MenABCWY, MenB -4C or MenACWYCRM\nNon- inferiority vs MenACWYCRM \nin MenACWY -naïve and -primed\nClinicaltrials.gov identifier NCT04502693 , accessed May 31st, 2024; Clinicaltrials.gov identifier  NCT04707391 , accessed May 31st, 2024; Vesikari T et al. Hum Vaccin Immunother .2021;17(11):4689 -4700Evidence Supporting Safety and Immunogenicity of MenABCWY \n20\nPresentation by GSK at ACIP, June 2024020406080100\nBaseline After 2 doses After 24m After booster020406080100\nBaseline After 2 doses After 24m After boosterNHBAMenB -4C 0,2m  (n=126) Persistence After 24 months and Booster Response of MenABCWY\nDemonstrated Against Serogroup B Reference Strains\nfHbp NadA\nPorA% with hSBA\ntiters\n≥ LLOQs\n*For follow -on group: blood draws were done at baseline and 5 days after booster dose. For the Matched Naive group: blood draws were baseline ( prevaccination), 1 month after 1st dose and 5 days after 2nd dose. fHbp, factor H binding protein; hSBA, serum \nbactericidal assay using human complement; LLOQ, lower limit of quantitation; NadA , Neisseria adhesin A; NHBA, Neisseria heparin binding antigen; PorA , porin A.  The LLOQs were 8.0 ( fHbp), 8.6 ( NadA ), 8.9 (NHBA), 8.2 ( PorA ).\nVesikari T et al. Hum Vaccin Immunother .2021;17(11):4689 -4700\nStudy 15E1 MenABCWY 0,6m  (n=74)\n% with hSBA\ntiters\n≥ LLOQs020406080100\nBaseline After 2 doses After 24m After booster020406080100\nBaseline After 2 doses After 24m After booster\nPrimary Study Extension Study* Primary Study Extension Study*\nPrimary Study Extension Study* Primary Study Extension Study*\n21\nPresentation by GSK at ACIP, June 2024\nCombines two well -established vaccines licensed in the US - MenB -4C, MenACWYCRM\nClinical program demonstrated safety and immunogenicity in adolescents and young \nadults\nTested against a broad panel of 110 serogroup B strains, representing 95% of US serogroup B disease-causing strains\n Demonstrated persistence of immune response up to 24 monthsMenABCWY  Summary\n22\nPresentation by GSK at ACIP, June 2024Summary of Data for Policy Considerations\n2 doses of MenABCWY can protect against serogroups A,B,C W,Y \nAchieves broad coverage against strains causing endemic and outbreak \ndisease, to meet the current and evolving US epidemiology\nOffers the opportunity to improve vaccination coverage in adolescents and young adults\nRepresents the evolution of IMD as one vaccine- preventable disease\nMenABCWY  allows for prevention of IMD with one vaccine \nThank you!\nInvestigators, study site personnel,\nstudy participants, and their families", "summary": "MenABCWY for the prevention of  Invasive Meningococcal Disease  caused by serogroups A, B, C, W and Y Wendy Sohn, MD Global Medical Lead Neisseria Vaccines 2 Presentation by GSK at ACIP, June 2024 Concerted Prevention of IMD in Adolescents and Young Adults Improve vaccination  coverage  rates5 to meet the  greatest medical needReduce overall burden  of pain and discomfort6 Improved convenience and  compliance6Potentially better  overall  economic value6Need for  pentavalent  vaccines 1.Mbaeyi…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/03-Mening-GSK-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 23}
{"title": "04 Mening Schillie 508", "content": "Work Group Considerations Regarding MenABCWY  Vaccine and \nDiscussion of Potential Risk Groups for MenB  Vaccination\nSarah F. Schillie , MD, MPH, MBA\nDBD/NCIRD\nAdvisory Committee on Immunization Practices\nJune 28, 2024\nThe findings and conclusions in this presentation are those of the authors and do not necessarily represent the official posi tion of the \nCenters for Disease Control and Prevention\nCONFIDENTIAL\nGSK’s MenABCWY Vaccine Clinical Development Program\nPhase 3 studies\n•V72_72:  ages 10 – 25 years, MenACWY- naïve/ MenB- naïve, N=3,638\n•87-9 1% White*; 3 -6%  Hispanic or Latino*; 49 -56% female\n•MenABCWY -0 19:  ages 15–25 years, MenACWY- primed/ MenB- naïve, N=1,247\n•75-76%  White*; 29- 31% Hispanic or Latino*; 52 -55% female\n•Comparators:  Me nACWY -CRM, MenB -4C 0,2 mo., MenB -4C 0,6 mo.\n10 Phase 1 and 2 studies\n*Demographics of participants reflect countries in which studies performed2 of 32\nAssessment of Safety\nPhase 3 studies\n•Solicited local and systemic AEs after each dose of Me nABCWY , MenACWY , and \nMenB\nIntegrated Safety Analysis (N=7,048)\n•Unsolicited AEs within 30 days of vaccination \n•Related, leading to withdrawal, medically attended, related medically attended, \nS\nAEs, deaths\nAE, adverse event; SAE, serious adverse event3 of 32\n4 of 32\n5 of 32\nSolicited AE:\n•Local AE:  Me nABCWY≈MenB and MenABCWY >MenACWY\n•Systemic AE:  MenABCWY≈MenB≈MenACWY\nUnsolicited AE:  \n•MenABCWY  s lightly greater than MenB and greater than \nMenACWY\n•Except for AE leading to withdrawal during the entire study period:  \nMe\nnABCWY≈MenB <MenACWY\nAE, adverse eventSolicited and Unsolicited AE Following Vaccination\n6 of 32\nSAEs and Deaths\nSAE during entire study period:  Me nABCWY≈MenB>MenACWY  \n(all ≤2%)\n•Related SAE during entire study period:   MenABCWY≈MenB >Me nACWY (all ≤0.1%)\n•4 of 5 resolved or partially resolved (seizure*, connective tissue disorder*, \nne\nuromyelitis optica *, pyrexia/nausea/vomiting/ headache¥)\n•1 ongoing (ulcerative colitis† with positive family history for Crohn’s disease)\nDeaths (all unrelated)\n•MenABCWY r ecipients (1):  suicide\n•MenB r ecipients (2):  drug overdose, poisoning\n•MenACWY r ecipients (1):  suicide\n*MenABCWY  vaccine recipient, ¥MenACWY  recipient, † MenB  recipient\nSAE, serious adverse event7 of 32\nImmunogenicity Assessment\nSerogroup A, C, W, Y\n•Seroresponse:  4- f old rise in hSBA  titers\nSerogroup B\n•Seroresponse:  4- f old rise in hSBA  titers\n•enc-h SBA  assay:  Assessment of protection against diverse disease-\ncausing serogroup B strains\n•110 randomly selected strains that represent 95% of U.S. “disease-\nc\nausing” strains\nenc- hSBA , endogenous complement hSBA8 of 32\n9 of 32\n2 doses Me nABCWY  non-\ninferior to 1 dose \nMenACWY\n•MenACWY- n aïve and primed \nrecipients\n10 of 32\n1 do se MenABCWY  non- inferior \nto 1 dose MenACWY  in \nMenACWY -primed recipients\n•Naïve recipients:  ad hoc analysis; \nconfidence intervals overlap for all 4 serogroups\n•Responses greater for MenABCWY \nrecipients compared to MenACWY \nrecipients\n•Except for serogroup A (rare in U.S.)\n11 of 32\n12 of 32\nMenABCWY  v s. MenB  0,2:\n•Success criterion met for 3 \no\nf 4 strains ( fHbp, NadA , \nNHBA)\n13 of 32\nMenABCWY  v s. MenB  0,6:\n•Success criterion met for 2\no\nf 4 strains ( fHbp, NadA )\n14 of 32\n15 of 32\n16 of 32\nImmunogenicity for Serogroup B:  enc- hSBA\nSuccess criterion met\n•Compared to M enB 0,2 and MenB 0,6\n•Test-b ased and responder- based IVE\nResponse slightly higher for Me nB vs. MenABCWY\n•Slightly higher for MenB 0,6 v s. MenB 0,2\nIVE, immunological vaccine effectiveness\n17 of 32\n18 of 32\nPersistence and Booster Response\n\n•\n•\n•\n\n•\n•MenB  \nAfter 24 months, titers waned substantially for B strains fHbp, NHBA, \nand PorA\nRobust booster response elicited\nConfidence intervals overlapped ( Me nABCWY  and MenB  0,2)\nMenACWY\nAfter 24 months, titers waned substantially for serogroup A; variable \nwaning noted for other serogroups\nRobust booster response elicited\n19 of 32\nSummary\nFavorable safety profile\n•Similar to Me nB (more adverse events for MenABCWY than MenACWY)\nImmunogenicity against serogroups A, C, W, Y\n•MenABCWY n on-inferior to MenACWY in most study groups\n•Comparison of 1 dose MenABCWY v s. 1 dose MenACWY in naïve recipients not \npowered for noninferiority; results favorable for all serogroups except A \nImmunogenicity against serogroup B strains\n•MenABCWY n on-inferior to MenB based on IVE\n•MenABCWY n on-inferior to MenB 0,2 for 3 strains and MenB 0,6 for 2 strains \nPersistence and booster response\n•After 24 months, titers waned substantially for serogroup A and for 3 B strains\n•Robust booster response elicitedIVE, immunologic vaccine effectiveness 20 of 32\nAdditional Work Group Reflections\nConcern about drop in protection at 2 years for serogroup B \ns\ntrains\nPorA  indic ator strain is important because it is not really PorA  \nalone but rather represents the full outer membrane vesicle component of the vaccine\n•Response to this indicator strain has bearing on cross -p rotection\n21 of 32\nPotential Risk Groups for \nMenB Vaccination\nSchedule Options Under Consideration\nOptionACWY \nDose#1ACWY Dose#2B Dose#1 B Dose#2\nCurrent \nrecomm .11–12 yrs 16 yrs16 yrs – 23 years (preferred 16–18 yrs) \nSCDM\n1 11–12 yrs 16 yrs 16 yrs 17–18 yrs\n2 11–12 yrs 16 yrs 16 yrs risk-based 17–18 yrs risk-based\n3 No dose 16 yrs 16 yrs risk -based 17–18 yrs risk-based\n4 15 yrs 17–18 yrs 17–18 yrs 17–18 yrs\n5 (ACIP) No dose 16 yrs 16 yrs 17–18 yrs \nProposed recommendations are for routine vaccination unless specified as “risk -based”; option numbers do not represent ordering of preference\nSCDM, shared clinical decision -making23 of 32\nIdentify Risk Groups for MenB  Vaccination\nBased on congregate living settings among \nad\nolescents\n•Recommendations will not address military/non- c ivilian \npopulations as per the ACIP charter\n24 of 32\n•College students (4 -y ear students, 1st year students, on- campus residence)\n•Boarding schools\n•Congregate foster care\n•Correctional or detention facilities\n•Homeless or emergency shelters\n•Institutions for persons with developmental disabilities\n•Psychiatric institutions\n•Residential treatment centers\n•Religious academies\n•Wilderness programs, summer camps\n•Seasonal worker housing (including agricultural workers)\n•College preparatory experiences\n•Hotels, motels, and hostelsPotential Risk Groups for MenB  Vaccination  \n25 of 32\n•College students (4 -y ear students, 1st year students, on- campus residence)\n•Boarding schools\n•Congregate foster care\n•Correctional or d etention  facilities\n•Homeless or emergency shelters\n•Institutions for persons with developmental disabilities\n•Psychiatric institutions\n•Residential treatment centers\n•Religious academies\n•Wilderness programs, summer camps\n•Seasonal worker housing (including agricultural workers)\n•College preparatory experiences\n•Hotels, motels, and hostelsDuration of Congregate Living Risk Should \nExceed Time to Complete Vaccine Series\n26 of 32\nFactors Associated with Increased Serogroup B Risk \namong College Students\n4-y ear college students had a 5.2-fold (95% CI: 3.6- 7.7) higher risk of serogroup B \ndisease than non- undergraduates aged 18 -24 years\n•Risk among 2 -y ear college students was comparable to non -undergraduates (RR 1.0, 95% CI \n0.4-2.1)\nFirst -y ear students were at 3.8- fold (95% CI: 2.4- 6.0) higher risk of serogroup B \ndisease than non- first-year students\nOn-c ampus residents were at 2.9-fold (95% CI: 1.8- 4.6) higher risk of serogroup B \ndisease than off- campus residents\nStudents participating in Greek life were at 9.8 -fold (95% CI: 4.6- 21.2) higher risk of \nserogroup B disease than other students during outbreaks\nWeil LW, Crowe SJ, Rubis AB, Soeters  HM, Meyer SA, Hariri S, McNamara LA. Risk Factors for Serogroup B Meningococcal Disease Among College Students, Open Forum Infectious \nDiseases. 2023; https://doi.org/10.1093/ofid/ofad607\n27 of 32\nCollege Students\nWork Group prefers to include all college students\n•Simplifies recommendations\n•College plans may change\n•Equity considerations\n28 of 32\nNumber of Students at U.S. Colleges and Boarding Schools\nNumber of 18 y ear-olds (in 2020):  4,159,857\nRecent high school completers* in 2022:  2,987,000\n•Percentage of recent high school completers enrolled in college:  62.0%\n•2-y ear college: 16.9%\n•4-y ear college or university:  45.1%\n>35,000 students enrolled in U.S. boarding schools\n•Older students, many may be likely to attend college\n*Includes those who completed a GED or other high school equivalency credential \nGED, General Educational Development\nBridged -Race Population Estimates 1990 -2020 Results Form (cdc.gov)\nNumber of recent high school completers and percent enrolled in college, by sex and level of institution: 1960 through 2022\nWhy Kids Go to Boarding School (usnews.com)29 of 32\nPublic Foster Care System\nContinuum of foster care\n•Includes children through 18 –2 1 years (varies by state) \n•Fo ster family home, group home, residential program\n•May or may not include congregate care settings\nPublic foster care system served 570,000 children in 2022\n•369,000 children in care on September 30, 2022 \nFederal law requires children to be placed in least restrictive, most \nf\namily-like setting\n•Number placed in congregate care decreasing\n•Those in congregate foster care typically spend ~8 months\nChildren’s Bureau, Administration for Children and Families, U.S. Department of Health and Human Services  Trends in Foster Care and Adoption: FY 2013 – 2022 | The \nAdministration for Children and Families (hhs.gov) 30 of 32\nInclusive Language\nWork Group prefers to add inclusive language to \nrisk-\ngroups\n•Such that any adolescent who desires protection may receive \nMe\nnB vaccine\n•Includes those who are unsure of their future plans ,  which may \ninform congregate living risk\n31 of 32\nRisk group includes adolescents planning to attend college and \na\ndolescents in a congregate living setting (e.g., congregate \nfoster care, boarding school, correctional facility, etc.) who are anticipated to remain in this setting long enough to complete the MenB vaccine series\nAny adolescent who desires protection may receive Me\n nB \nvaccine, even if they are unsure of their future plans  which \nmay inform congregate living riskProposed Language\n32 of 32", "summary": "Work Group Considerations Regarding MenABCWY  Vaccine and  Discussion of Potential Risk Groups for MenB  Vaccination Sarah F. Schillie , MD, MPH, MBA DBD/NCIRD Advisory Committee on Immunization Practices June 28, 2024 The findings and conclusions in this presentation are those of the authors and do not necessarily represent the official posi tion of the  Centers for Disease Control and Prevention CONFIDENTIAL GSK’s MenABCWY Vaccine Clinical Development Program Phase 3 studies •V72_72:  ages…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-june-26-28-2024.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2024-06-26-28/04-Mening-Schillie-508.pdf", "doc_date": "2024-06-26", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 32}
{"title": "Dengue 02 Biswal 508", "content": "TAK-003 (Tetravalent Dengue Vaccine Candidate) \n23 February 2023 \nShibadas Biswal, MD \nSenior Medical Director – Clinical Development Dengue \nTakeda Vaccines \n9 Efficacy and safety of a tetravalent dengue vaccine (TAK-003) \nVV-MEDMAT-82307 \n                  \n \n                  \n        \n             \n           \n    \n         Disclaimers \n• TAK-003 is an investigational compound that has not been approved for use by the US Food and Drug \nAdministration \n• There is no guarantee TAK-003 will be approved in any country or countries for use in indications under investigation in the trials or studies discussed herein \n• Regulatory approval and use of TAK-003 is dependent on review by relevant local authorities \n– Currently, TAK-003 is approved for use in Indonesia, the EU, and UK \nACIP, Advisory Committee on Immunization Practices. \n10 Efficacy and safety of a tetravalent dengue vaccine (TAK-003) \n\n   \n  \n    \n      \n        \n         \n         Topics to be covered \n• Construct of the vaccine \n• Immune response profile \n• Overview of the clinical development \n• Efficacy profile from the pivotal efficacy trial \n• Safety profile from an integrated analysis of placebo-controlled trials \n• Immunogenicity data from the pivotal efficacy trial \n• Summary \n11 Efficacy and safety of a tetravalent dengue vaccine (TAK-003) \n\nTAK-003 is based on a live, attenuated DENV-2 virus backbone \nexpressing E and prM proteins of all four DENV serotypes \nGenetic structure and design of TAK-0031–3 \nThre  e attenuatin  g mutations2 \n          \n        \n     \n         \nAttenuated  TDV-  2 \nSubstitutio  n with  prM  and  E  gene  s \nfro  m DENV-1,  -3,  and  -4 \nTDV-1 \nTDV-3 \nTDV-4 \nC , capsid;  DENV  , dengue  virus;  E , envelope;  NS , non-structural;  pr  M, pre-membrane;  TDV  , tetravalent  dengue  vaccine.  \n1.  Osorio  JE , et  al.  Expert  Rev  Vaccine  s 2016;15:497–508;  2.  Osorio  JE , et  al.  Vaccine 2015;33:7112–7120;  3.  Pate  l SS , et  al.  Clin  Infect  Dis 2022.  doi:10.1093/cid/ciac41  8 [Epub ahead  of  print]. \n12 Efficacy and safety of a tetravalent dengue vaccine (TAK-003) \n\n \n       \n           \n           \n \n       \n \n            \n        \n                \n                              \n               \n         In clinical trials, TAK-003 activated multiple facets of immunity \nHumoral-mediated immunity • TAK-003 elicited neutralizing antibodies against each of DENV-1,-2,-3,-4\n1,2 \n• TAK-003 elicited cross-reactive antibodies that blocked the activity of DENV NS1 protein3 \n• TAK-003 elicited type-specific memory B cells that target DENV-1, -2, -3, -4*4 \nCell-mediated immunity • TAK-003 stimulated cross-reactive CD4+ and CD8+ T-cell responses\n5 \nInnate immunity • TAK-003 stimulated production of T cells capable of producing IFNγ, TNFα, and IL-2\n5 \nA broad  spectrum  of immune  responses  may  contribute  to protection  against  infection, \nvirus  clearance,  and prevention  of severe  disease1–5 \n*These data were gathered from non-human primates and humans. \nCD, cluster of differentiation; DENV, dengue virus; IFN, interferon; IL, interleukin; NS, non-structural; TNF, tumor necrosis factor. 1. Biswal S, et al. Lancet 2020;395:1423–1433; 2. Tricou V, et al. Lancet 2020;395:1434–1443; 3. Sharma M, et al. J Infect Dis 2020;221:867–877; 4. Michlmayr D, et al. J Infect Dis 2021;233:247–257; \n5. Tricou V, et al. Vaccine 2022;40:1143–1151. \n13 Efficacy and safety of a tetravalent dengue vaccine (TAK-003) \n\n                 \n                  \n                   \n                        \n                   \n                        \n                   \n                        \n                 \n                   \n           \n          \n        Overview of the clinical development program \n• 19 clinical trials conducted in 13 dengue endemic and non-endemic countries \n• Over 28,000 children/adults (aged 1.5–60 years) participated in Phase I–III clinical studies \n• Clinical development included both baseline seronegative and seropositive participants \n• ~20,000 participants received at least one dose of TAK-003 \nAb, antibody; CMI, cell-mediated immunity; HepA, hepatitis A; HPV9, human papillomavirus 9 vaccine; S&I, safety and immunogenicity. \n1. ClinicalTrials.gov NCT01110551. Available at: https://www.clinicaltrials.gov/ct2/show/NCT01110551 (accessed January 2023); 2. ClinicalTrials.gov NCT01224639. Available at: https://www.clinicaltrials.gov/ct2/show/NCT01224639 (accessed January 2023); 3. ClinicalTrials.gov NCT01765426. Available at: \nhttps://www.clinicaltrials.gov/ct2/show/NCT01765426 (accessed January 2023); 4. ClinicalTrials.gov NCT01542632. Available at: https://www.clinicaltrials.gov/ct2/show/NCT01542632 (accessed January 2023); 5. ClinicalTrials.gov NCT01728792. Available at: https://www.clinicaltrials.gov/ct2/show/NCT01728792 (accessed \nJanuary 2023); 6. ClinicalTrials.gov NCT02193087. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02193087 (accessed January 2023); 7. ClinicalTrials.gov NCT01511250. Available at: https://www.clinicaltrials.gov/ct2/show/NCT01511250 (accessed January 2023); 8. ClinicalTrials.gov NCT02302066. Available at: \nhttps://www.clinicaltrials.gov/ct2/show/NCT02302066 (accessed January 2023); 9. ClinicalTrials.gov NCT02425098. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02425098 (accessed January 2023); 10. ClinicalTrials.gov NCT02747927. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02747927 (accessed \nJanuary 2023); 11. ClinicalTrials.gov NCT02948829. Available at: https://www.clinicaltrials.gov/ct2/show/NCT02948829 (accessed January 2023); 12. ClinicalTrials.gov NCT03999996. Available at: https://www.clinicaltrials.gov/ct2/show/NCT03999996 (accessed January 2023); 13. ClinicalTrials.gov NCT03423173. Available at: \nhttps://www.clinicaltrials.gov/ct2/show/NCT03423173 (accessed January 2023); 14. ClinicalTrials.gov NCT03341637. Available at: https://www.clinicaltrials.gov/ct2/show/NCT03341637 (accessed January 2023); 15. ClinicalTrials.gov NCT03771963. Available at: https://www.clinicaltrials.gov/ct2/show/NCT03771963 (accessed \nJanuary 2023); 16. ClinicalTrials.gov NCT03746015. Available at: https://www.clinicaltrials.gov/ct2/show/NCT03746015 (accessed January 2023); 17. ClinicalTrials.gov NCT03342898. Available at: https://www.clinicaltrials.gov/ct2/show/NCT03342898 (accessed January 2023); 18. ClinicalTrials.gov NCT03525119. Available at: \nhttps://www.clinicaltrials.gov/ct2/show/NCT03525119 (accessed January 2023); 19. ClinicalTrials.gov NCT04313244. Available at: https://www.clinicaltrials.gov/ct2/show/NCT04313244 (accessed January 2023). \n14 Efficacy and safety of a tetravalent dengue vaccine (TAK-003) \n\n         \n                       \n                      TIDES (DEN-301): Pivotal Phase III trial design \n20,071 children (aged 4–16 years) received either TAK-003 or placebo in a 2:1 ratio1,2 \nRT-PCR, reverse transcriptase polymerase chain reaction; SAE, serious adverse event. \n1. ClinicalTrials.gov NCT02747927. Available at: https://clinicaltrials.gov/ct2/show/NCT02747927 (accessed January 2023); 2. Biswal S, et al. N Engl J Med 2019;281:2009–2019. \n15 Efficacy and safety of a tetravalent dengue vaccine (TAK-003) \n\n                   \n           \n                      \n     \n         \n           \n    \n     \n     \n     \n     \n    \n     =-\n=Demographic and baseline characteristics: Safety set \nCharacteristic Placebo \nn 6687 TAK 003 \nn 13,380 \nSeronegative, n (%) 1832 (27.4) 3714 (27.8) \nMean age, years (SD) 9.6 (3.34) 9.6 (3.36) \n4–5 years, n (%) 846 (12.7) 1702 (12.7) \n6–11 years, n (%) 3697 (55.3) 7387 (55.2) \n12–16 years, n (%) 2144 (32.1) 4291 (32.1) \nAsia, n (%) 2993 (44.8) 5996 (44.8) \nLatin America, n (%) 3694 (55.2) 7384 (55.2) \nBaseline serostatus data were available for 6684 and 13,375 safety set participants in the placebo and TAK-003 groups, respectively. \nn refers to number of participants in the safety analysis set. Seronegative at baseline: seronegative to all four DENV serotypes. Seropositive at baseline: reciprocal neutralizing titer ≥10 for one or more DENV serotypes. DENV, dengue virus; SD, standard deviation. \nTakeda. Data on file. \n16 Efficacy and safety of a tetravalent dengue vaccine (TAK-003) \n\n           \n                                           \n              \n   \n    \nDominican \nNicaragua Republic LATAM2 APAC2 \nPhilippines \nColombia \nPanama Cases of VCD, nThailand Sri Lanka \nBrazil \nCases of VCD, n \nSerotype of infection Serotype of infection        \nTrial sites and background dengue cases in the placebo group \nUp to 57 months post 1st dose: Safety set1 \nAPAC, Asia-Pacific; DENV, dengue virus; LATAM, Latin America; VCD, virologically confirmed dengue. \n1. 1. Tricou V, et al. Efficacy and safety of Takeda’s tetravalent dengue vaccine candidate (TAK-003) after 4.5 years of follow-up. Presented at NECTM, Rotterdam, Netherlands, 8–10 June 2022; 2. Takeda. Data on File. \n17 Efficacy and safety of a tetravalent dengue vaccine (TAK-003) \n     \n                             \n    Primary and secondary efficacy endpoint analysis \nVaccine efficacy = 1 – hazard ratio (TAK-003 vs. placebo). Hazard ratio estimated from Cox proportional hazards model with adjustment for \nage and stratified by region. \n18 Efficacy and safety of a tetravalent dengue vaccine (TAK-003) \n\n   \n                     \n                     \n                     \n                         \n                     \n DEN-301: Primary and secondary endpoints \nPrimary and secondary endpoints per protocol set data; placebo to TAK-003 1:2 randomization1–3 \nVCD (per 100 person-years) \n-80 -60 -40 -20 0 20 40 60 80 100 \nVE (%) \nVE against VCD by any serotype in the 30 days to 18 months post 2nd dose time frame was an exploratory endpoint; \nSeronegative at baseline: seronegative to all four DENV serotypes; seropositive at baseline: reciprocal neutralizing titer ≥10 for one or more DENV serotypes. \nCI, confidence interval; DCAC, Dengue Case Adjudication Committee; DENV, dengue virus; DHF, dengue hemorrhagic fever; VCD, virologically confirmed dengue; VE, vaccine efficacy. \n1. Biswal S, et al. Lancet 2020;395:1423–1433; 2. Biswal S, et al. N Engl J Med 2019;381:2009–2019; 3. Takeda. Data on File. \n19 Efficacy and safety of a tetravalent dengue vaccine (TAK-003) \nPlacebo TAK-003 \nEndpoint n=6317 n=12,704 VE  95% CI \n  30 days  to  12  months post 2nd   dose  (primary endpoint) \n   VCD by any serotype  149 (2.6)  61 (0.5) 80.2  (73.3, 85.3) \n  30 days  to  18  months post 2nd   dose  (secondary endpoint) \n      VCD leading to hospitalization (key secondary endpoint)  66 (0.8)  13 (<0.1) 90.4  (82.6, 94.7) \n   VCD by any serotype  206 (2.4)  114 (0.6) 73.3  (66.5, 78.8) \n Baseline seropositive  150 (2.4)  75 (0.6) 76.1  (68.5, 81.9) \n Baseline seronegative  56 (2.4)  39 (0.8) 66.2  (49.1, 77.5) \n  VCD by DENV-1  62 (0.7)  38 (0.2) 69.8  (54.8, 79.9) \n  VCD by DENV-2  80 (0.9)  8 (<0.1) 95.1  (89.9, 97.6) \n  VCD by DENV-3  60 (0.7)  63 (0.4) 48.9  (27.2, 64.1) \n  VCD by DENV-4  5 (<0.1)  5 (<0.1)  51.0 (−69.4, 85.8) \n  DCAC-defined severe VCD  1 (<0.1)  2 (<0.1)  2.3 (−997.5, 91.1) \nDHF  7 (<0.1)  2 (<0.1) 85.9  (31.9, 97.1) \n      \n  \n                             \n    Cumulative efficacy results over ~57 months \n(safety set data) \nVaccine efficacy = 1 – hazard ratio (TAK-003 vs. placebo). Hazard ratio estimated from Cox proportional hazards model with adjustment for \nage and stratified by region. \n20 Efficacy and safety of a tetravalent dengue vaccine (TAK-003) \n\nTAK-003 was efficacious against VCD over 57 months regardless of \nbaseline serostatus \nCumulative incidence of participants \nwith VCD (%) 10 \n8 \n6 4 2 \n0 \nPlacebo \nTAK-003 \nPlacebo \nTAK-003 Seropositive \nSeronegative \n0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 \nTime since 1st dose (months)     \n  \n   Cumulative safety data set1 \nVE (95% CI) \n                               \n         \n                                     \n \n            \n  \n  \n  \n  Overall 61.2 (56.0, 65.8) \nSeronegative 53.5 (41.6, 62.9) \nSeropositive 64.2 (58.4, 69.2) \nSafety set data truncated at 57 months post 1st dose. Seronegative at baseline: seronegative to all four DENV serotypes; seropositive at baseline: reciprocal neutralizing titer ≥10 for one or more DENV serotypes. \nCI, confidence interval; DENV, dengue virus; VCD, virologically confirmed dengue. \n1. Tricou V, et al. Efficacy and safety of Takeda’s tetravalent dengue vaccine candidate (TAK-003) after 4.5 years of follow-up. Presented at NECTM, Rotterdam, Netherlands, 8–10 June 2022. \n21 Efficacy and safety of a tetravalent dengue vaccine (TAK-003) \n\n    \n   \n   \n2.5 \n2.0 participants\nCD (%) of \nd V1.5 nce \nizeincide1.0 lative \nwith hospital0.5 Cumu0.0 \n0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 \nTime since 1st dose (months) Placebo \nTAK-003 \nPlacebo \nTAK-003 Seropositive \nSeronegative \n                              \n         \n                                    \n   \n            \n  \n  \n  \nTAK-003 was efficacious against hospitalized VCD over 57 months \nregardless of baseline serostatus \nCumulative safety data set1 \nVE  (95%  CI) \nOverall 84. 1(77.8, 88.6) \nSeronegative 79. 3(63.5, 88.2) \nSeropositive 85. 9(78.7, 90.7) \nSafety set data truncated at 57 months post 1st dose. Seronegative at baseline: seronegative to all four DENV serotypes; seropositive at baseline: reciprocal neutralizing titer ≥10 for one or more DENV serotypes. \nCI, confidence interval; DENV, dengue virus; VCD, virologically confirmed dengue. \n1. Tricou V, et al. Efficacy and safety of Takeda’s tetravalent dengue vaccine candidate (TAK-003) after 4.5 years of follow-up. Presented at NECTM, Rotterdam, Netherlands, 8–10 June 2022. \n22 Efficacy and safety of a tetravalent dengue vaccine (TAK-003) \n                        \n               \n                     \n            \n                                       \n           \n     \n \n \n \n  \n  \n  \n  \n   \n   \n  \n \n \n   \n  \n          \n=-\n=Efficacy against VCD: By baseline serostatus and serotype \n1st dose to end of Part 3: Safety set (~57 months)1,2 \nPlacebo \nn 6687 TAK 003 \nn 13,380 VE (95% CI) \nVCD, n (per 100 person-years) \nSeropositive \nDENV-1 DENV-2 DENV-3 DENV-4 151 (0.7) 135 (0.6) \n97 (0.4) \n20 (<0.1) 133 (0.3) \n54 (0.1) 96 (0.2) \n12 (<0.1) 56.1 (44.6, 65.2) \n80.4 (73.1, 85.7) \n52.3 (36.7, 64.0) \n70.6 (39.9, 85.6) \nSeronegative \nDENV-1 DENV-2 DENV-3 DENV-4 79 (1.0) 58 (0.7) 16 (0.2) \n3 (<0.1) 89 (0.5) \n14 (<0.1) \n36 (0.2) \n12 (<0.1) 45.4 (26.1, 59.7) \n88.1 (78.6, 93.3) \n−15.5 (−108.2, 35.9) \n−105.6 (−628.7, 42.0) \nn refers to number of participants in the safety set. Numbers of VCD (per 100 person-years) are based on the number of participants evaluated. \nRepeat episodes of VCD were excluded from efficacy analysis at VCD or serotype level as applicable. Seronegative at baseline: seronegative to all four DENV serotypes. Seropositive at baseline: reciprocal neutralizing titer ≥10 for one or more DENV serotypes. \nCI, confidence interval; DENV, dengue virus; VCD, virologically confirmed dengue; VE, vaccine efficacy. \n1. Tricou V, et al. Efficacy and safety of Takeda’s tetravalent dengue vaccine candidate (TAK-003) after 4.5 years of follow-up. Presented at NECTM, Rotterdam, Netherlands, 8–10 June 2022; 2. Takeda. Data on File. \n23 Efficacy and safety of a tetravalent dengue vaccine (TAK-003) \n\n  \n      \n \n \n \n  \n  \n   \n     \n  \n  \n   \n \n \n  \n \n  \n \n                         \n         \n                        \n                      \n              \n                                       \n \n                  \n=-\n=Efficacy against hospitalized VCD: By baseline serostatus \nand serotype \n1st dose to end of Part 3: Safety set (~57 months)1,2 \nPlacebo \nn 6687 TAK 003 \nn 13,380 VE (95% CI) \nHospitalized VCD, n (per 100 person-years) \nSeropositive \nDENV-1 \nDENV-2 DENV-3 DENV-4 24 (0.1) 59 (0.3) \n15 (<0.1) \n3 (<0.1) 16 (<0.1) \n5 (<0.1) 8 (<0.1) \n0 (0.0) 66.8 (37.4, 82.3) \n95.8 (89.6, 98.3) \n74.0 (38.6, 89.0) \n100 (NE, NE) \nSeronegative \nDENV-1 DENV-2 DENV-3 DENV-4 14 (0.2) 23 (0.3) 3 (<0.1) 1 (<0.1) 6 (<0.1) \n0 (0.0) \n11 (<0.1) \n0 (0.0) 78.4 (43.9, 91.7) \n100 (NE, NE) \n−87.9 (−573.4, 47.6) \n100 (NE, NE) \nRate of hospitalization among VCD cases in placebo group : The Philippines, 17/191 ( 8.9% ); Sri Lanka, 70/103 ( 68.0% ); Thailand, 25/64 ( 39.1% ); Brazil, 2/24 ( 8.3% ); Colombia, 14/87 ( 16.1% ); \nDominican Republic, 4/22 ( 18.2% ); Nicaragua, 8/24 ( 33.3% ); Panama, 2/45 ( 4.4% ). \nn refers to number of participants in the safety set. Numbers of hospitalized VCD (per 100 person-years) are based on the number of participants evaluated. \nSeronegative at baseline: seronegative to all four DENV serotypes. Seropositive at baseline: reciprocal neutralizing titer ≥10 for one or more DENV serotypes. \nCI, confidence interval; DENV, dengue virus; NE, non-estimable; VCD, virologically confirmed dengue; VE, vaccine efficacy. \n1. Tricou V, et al. Efficacy and safety of Takeda’s tetravalent dengue vaccine candidate (TAK-003) after 4.5 years of follow-up. Presented at NECTM, Rotterdam, Netherlands, 8–10 June 2022; 2. Takeda. Data on File. \n24 Efficacy and safety of a tetravalent dengue vaccine (TAK-003) \n\n   \n                                       \n         \n      \n               Rate of hospitalization among VCD cases by country \nPlacebo group analysis 1st dose to end of Part 3 safety set (~57 months)1,2 \n0 10 20 30 40 50 60 70 80 Rate of hospitalization among VCD cases \nin placebo group (%) 8.9 68.0 \n39.1 \n8.3 16.1 18.2 33.3 \n4.4 \n1 2 3 4 5 6 7 8 \nVCD, virologically confirmed dengue. \n1. Tricou V, et al. Efficacy and safety of Takeda’s tetravalent dengue vaccine candidate (TAK-003) after 4.5 years of follow-up. Presented at NECTM, Rotterdam, Netherlands, 8–10 June 2022; 2. Takeda. Data on File. \n25 Efficacy and safety of a tetravalent dengue vaccine (TAK-003) \n\n                            \n      \n                        \n                      \n              \n           \n \n           \n      \nSeropositive \nDENV-1  22 (0.1)  11 (<0.1)  75.1 (48.7, 87.9) \nDENV-2  18 (<0.1)  2 (<0.1)  94.4 (76.0, 98.7) \nDENV-3  11 (<0.1)  5 (<0.1)   78.3 (37.4, 92.4) \nDENV-4  2 (<0.1)  0 (0.0)   100 (NE, NE) \nSeronegative \nDENV-1  12 (0.2)  5 (<0.1)  78.9 (40.1, 92.6) \nDENV-2  3 (<0.1)  0 (0.0)  100 (NE, NE) \nDENV-3  3 (<0.1)  5 (<0.1)   15.3 (−254.4, 79.8) \nDENV-4  1 (<0.1)  0 (0.0)  100 (NE, NE)          \n=-\n=Efficacy against hospitalized VCD: by baseline serostatus \nand serotype \n1st dose to end of Part 3: Safety set (~57 months)1 \nSensitivity  analysis  excluding  data  from  Sri Lanka \nPlacebo \nn 5987 TAK 003 \nn 11,986 VE (95% CI) \nHospitalized VCD, n (per 100 person-years) \nRate of hospitalization among VCD cases in placebo group : The Philippines, 17/191 ( 8.9% ); Sri Lanka, 70/103 ( 68.0% ); Thailand, 25/64 ( 39.1% ); Brazil, 2/24 ( 8.3% ); Colombia, 14/87 ( 16.1% ); Dominican Republic, 4/22 \n(18.2% ); Nicaragua, 8/24 ( 33.3% ); Panama, 2/45 ( 4.4% ). \nn refers to number of participants in the safety set. Numbers of hospitalized VCD (per 100 person-years) are based on the number of participants evaluated. \nSeronegative at baseline: seronegative to all four DENV serotypes. Seropositive at baseline: reciprocal neutralizing titer ≥10 for one or more DENV serotypes. \nCI, confidence interval; DENV, dengue virus; NE, non-estimable; VCD, virologically confirmed dengue; VE, vaccine efficacy. \n1. Takeda. Data on File. \n26 Efficacy and safety of a tetravalent dengue vaccine (TAK-003) \n\n      \n         Safety: Integrated analysis of placebo-controlled trials \n27 Efficacy and safety of a tetravalent dengue vaccine (TAK-003) \n\n        \n          \n            \n                             \n  \n              \n                            \n         \n                   \n     Integrated safety analysis \nSolicited local (within 7 days), systemic (within 14 days), and unsolicited (within 28 days) AEs \nin participants aged 4–60 years old1,2 \n• Solicited reactions occurred more frequently in the TAK-003 arm \n• Similar reporting of unsolicited AEs in the TAK-003 and placebo arms \n• Most frequent TAK-003-related unsolicited AEs: injection-site pruritus (0.7%), bruising (0.6%), and pyrexia (0.2%) \n43.4 46.1 \n21.3 \n3.0 25.7 40.1 \n22.8 \n1.7 \n0 10 20 30 40 50 60 70 80 90 100 Participants (%) AEs after any dose \n1 2 3 4 \nSeries1 Series2 \n*Injection-site pain, erythema, and swelling; †For adults and children ≥6 years old: headache, myalgia, malaise, asthenia, and fever; for children <6 years old: irritability/fussiness, drowsiness, loss of appetite, and fever. \nAE, adverse event. \nSolicited AEs: n=3783 (TAK-003) and n=1703 (placebo); Unsolicited AEs: n=3830 (TAK-003) and n=1725 (placebo). \n1. Patel S. Presented at ASTMH 2021, National Harbor, MD, US, 17–21 November 2021; 2. Takeda. Data on File: Integrated safety analysis of placebo-controlled trials, Takeda. \n28 Efficacy and safety of a tetravalent dengue vaccine (TAK-003) \n\n                             \n                         \n      \n           \n                       \n             -TAK 003 \n=n 14,627 Placebo \n=n 7167 \n Any SAE  1169 (7.99)  691 (9.64) \n Any  related SAE  1 (<0.01)  4 (0.06) \n SAEs   (by preferred  term)   experienced by >0.2%  of participants \nAppendicitis \n†  Dengue fever 104 (0.71) \n 77 (0.53)  48 (0.67) \n 144 (2.01) \nGastroenteritis  52 (0.36)  21 (0.29) \n Viral infection \n Asymptomatic COVID-19‡  41 (0.28) \n 37 (0.25)  40 (0.56) \n 13 (0.18) \nPneumonia  36 (0.25)  24 (0.33) \n  Urinary tract infection \nCOVID-19‡  34 (0.23) \n 32 (0.22)  21 (0.29) \n 11 (0.15) \nInfluenza DHF\n†  31 (0.21) \n 14 (0.10)  20 (0.28) \n 37 (0.52)       \n   \n      \n      \n     \n     \n  \n     Integrated safety analysis: SAEs \nParticipants with event, n (%)* \nOne SAE was considered related to \nTAK-003, compared with \nfive related SAEs in four placebo \nrecipients \nDeaths** \n• 16 (0.09%) in the TAK-003 group \n•\n 9 (0.11%) in the placebo group \n•\n None were considered related to \nt\nhe investigational product \n• No fatal cases of dengue occurred \n*Placebo-controlled trials pool; includes SAEs up to 54 months post 2nd dose in DEN-301; †As reported by investigators: not necessarily virologically confirmed dengue fever or meeting WHO 97 DHF criteria; \n‡As per local practice in Sri Lanka and Thailand, symptomatic and asymptomatic COVID-19-positive participants were isolated in designated centers/hospitals, and therefore, cases met SAE criteria; \n**All trials pool: n=16,919 (TAK-003), n=8381 (placebo). \nDHF, dengue hemorrhagic fever; SAE, serious adverse event; WHO, World Health Organization. Takeda. Data on File: Integrated safety analysis of placebo-controlled trials including data from DEN-301 up to end of Part 3. \n29 Efficacy and safety of a tetravalent dengue vaccine (TAK-003) \n\n     \n         Immunogenicity in baseline seronegative participants \n30 Efficacy and safety of a tetravalent dengue vaccine (TAK-003) \n\n                   \n    \n          \n      \n                                  Seropositivity rate across serotypes at Month 1 and Month 4 in the TAK-003 group \n(n=702) \n100 99.5 98.6 100.0 96.1 100.0 99.8 99.5 \n80 \n60 40 20 \n0 \n1 2 3 4 5 6 7 8 9 10 94.1 90.5 85.3 Seropositivity rate (%) Immunogenicity data: Seropositivity rate \nPPSI – participants seronegative at baseline in pivotal efficacy trial (TIDES) \nPPSI: number of participants evaluated at each time point may vary. Percentages are based on the number of participants evaluated. \nSeropositive: reciprocal neutralizing titer ≥10. DENV, dengue virus; M, month; PPSI, per protocol set of immunogenicity. \nTakeda. Data on File. \n31 Efficacy and safety of a tetravalent dengue vaccine (TAK-003) \n\n                   \n                          \n            \n   \n             \n  \n \n \n-Baseline seronegative 10,000 \n1000 \n100 TAK-003 group \nPlacebo group 10 \n1 \n0 1 3 4 9 15 27 39 51 PPSI analysis set TAK 003 Placebo \nBaseline seronegatives n=702 n=345 \nMonths after 1st vaccination \n        Immunogenicity  data:  GMT  * \nPPSI  – participants  seronegative  a t baseline  in  pivotal  efficac  y trial  (TIDES) GMT \nDENV-1 placebo DENV-1 TAK-003 DENV-2 placebo DENV-2 TAK-003 DENV-3 placebo DENV-3 TAK-003 DENV-4 placebo DENV-4 TAK-003 \nPPSI: number of participants evaluated at each time point may vary. Percentages are based on the number of participants evaluated. \n*Titers expressed as the reciprocal of the highest dilution of test serum that shows a 50% reduction in plaque counts compared with that of virus controls. DENV, dengue virus; GMT, geometric mean titer; PPSI, per protocol set of immunogenicity. \nTakeda. Data on File. \n32 Efficacy and safety of a tetravalent dengue vaccine (TAK-003) \n\n      \n          \n         \n          \n        \n        \n   \n      \n         \n                  \n    \n      \n        \n     \n      \n         Summary \n• Data from the TIDES pivotal trial showed: \n– Long-term efficacy of TAK-003 in both baseline seronegative and seropositive participants \n– TAK-003 is immunogenic against each of DENV-1, -2,-3, -4 serotypes \n• Data from pivotal trial suggested varying TAK-003 efficacy profiles by serotype \n– Efficacious against all four serotypes in baseline seropositive participants \n– Efficacious against DENV-1 and DENV-2 in baseline seronegative participants \n– Among baseline seronegative participants: \no \no \no \no D ata suggested lack of efficacy against DENV-3 \nT\nhe trial did not allow assessment of DENV-4 due to low incidence \nLong-term follow-up did not conclude a higher risk of hospitalized or severe forms of dengue associated with TAK-003 \nand DENV-3 or -4 serotype \nTotality of data did not indicate harm \n• Safety data from integrated analysis of placebo-controlled trials showed: \n– TAK-003 had an acceptable safety profile \nDENV, dengue virus. Takeda. Data on File. \n33 Efficacy and safety of a tetravalent dengue vaccine (TAK-003) \n\n \n         Thank you \n34 Efficacy and safety of a tetravalent dengue vaccine (TAK-003)", "summary": "TAK-003 (Tetravalent Dengue Vaccine Candidate)  23 February 2023  Shibadas Biswal, MD  Senior Medical Director – Clinical Development Dengue  Takeda Vaccines  9 Efficacy and safety of a tetravalent dengue vaccine (TAK-003)  VV-MEDMAT-82307                                                                                           Disclaimers  • TAK-003 is an investigational compound that has not been approved for use by the US Food and Drug  Administration  • There is no guarantee TAK-003 will…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/Dengue-02-Biswal-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 26}
{"title": "Dengue 03 Paz Bailey 508", "content": "WW Woo orr rkk kGG Grr roo ouu upp pSS Suu umm mmm maa arr ryy yaa ann ndd d\nII Inn ntt tee err rpp prr ree ett taa att tii ioo onn noo off fTT TAA AKK K-- -00 000 033 3EE Eff fff fii icc caa acc cyy y,, ,\nSS Saa aff fee ett tyy y,, ,aa ann ndd dII Imm mmm muu unn noo ogg gee enn nii icc cii itt tyy yDD Daa att taa aWork Group Summary and \nInterpretation of TAK-003 Efficacy, \nSafety, and Immunogenicity Data \nGabriela Paz-Bailey, MD, PhD, MSc \nDengue Branch Chief \nDivision of Vector Borne Diseases, NCEZID, CDC \n   \n   \n        \n   \n           \n \n     Phase 3 Study (DEN-301) \n• Design : double-blind, placebo-controlled study \n• Randomized to TAK-003 or placebo in a 2:1 ratio \n• Ages: children 4–16 years \n• Sites: conducted across 5 countries in Latin America and 3 countries \nin Asia \n• Duration : ~57 months after first dose \n    \n    \n      \n        \n      \n       \n  \n     \n   \n               DEN-301 population and outcomes evaluated \n• Safety set included 20,071 participants. \n• 28% of participants were seronegative at baseline. \n• Primary endpoint was virologically-confirmed dengue (VCD) from any \nserotype one year after the second dose.* \n• Secondary endpoints, stratified by serotype and serostatus, included: \n• VCD \n• Hospitalization for dengue \n• Dengue hemorrhagic fever (1997 WHO definition) \n• Trial-specific severe dengue definition \n*Exploratory endpoints were analyzed using the per protocol set (19,021 participants; 28% seronegative). Biswal, Lancet 2020. \n         \n  \n    \n     All VE data shown in the following summary are for: \n~57 months follow-up \nand \ninclude all RCT trial sites* \n*Participants included from the safety set. \n  VE for VCD \nDENV-2  80.4% (73.1, 85.7%) \nDENV-3  52.3% (36.7, 64.0%) \nDENV-4  70.6% (39.9, 85.6%)  \n \n \n                  \n          Overall VE \n61.2% (56.0,  65.8%) \nVE in Seronegatives \n53.5% (41.6–62.9%) \nVE in Seropositives by  Serotype VE in Seronegatives by  Serotype \nDENV-1 45.4% (26.1,  5 9.7%) Vaccine  Efficacy* Outcome  : Virologically  Confirmed  Dengue \nVE in Seropositives \n64.2% (58.4,  69.2%) \nDENV- 2 88.1% (78.6, 93.3%) \nDENV-3 -15.5% (-108.2, 35.9%) \nDENV-4 -105.6% (-628.7, 42.0%) \n*57 months after first dose, s ignificant results bolded. Number for seropositive placebo \nparticipants 4,855 and vaccine 9,666; Seronegative placebo 1,832 and vaccine 3,714. Unpublished data presented by Takeda to ACIP WG DENV-1  56.1% (44.6, 65.2%) \n      \n    \n    \n     \n           SS Suu umm mmm maa arr ryy y:: : Summary: Virologically Confirmed Dengue \n• Seropositives \n• Protection against all 4 serotypes. \n• Seronegatives \n• Protection against DENV-1 and -2. \n• No efficacy for DENV-3 and -4. \n• Data insufficient to rule out an increased risk of VCD among vaccinees. \n  VE for hospitalization \nDENV-2  \n 95.8% (89.6, 98.3%) \nDENV-3 \nDENV-4   74.0% (38.6, 89.0%) \nNE)†  100% (NE,DENV\n-2 100% NE)§  (NE,\nDENV-3 -87.9% 47.6%)¶  (-573.4, \nDENV-4  100 %  (NE, NE)** \n              \n     \n     \n           \n                 Overall  VE \n84.1%  (77.8, 88.6%)  \nVE in Seropositives by  Serotype VE in Seronegatives by  Serotype Vaccine  Efficacy* Outcome  : Hospitalization \nVE in Seropositives \n85.9%  (78.7,  90.7%) \n†DENV-4 Placebo events: 3 TAK-003 events: 0 \n*57 months after first dose, s ignificant results bolded. Number for seropositive placebo \nparticipants 4,855 and vaccine 9,666; Seronegative placebo 1,832 and vaccine 3,714. §DENV-2 Placebo events: 23 TAK-003 events: 0 \n¶DENV-3 Placebo events: 3 TAK-003 events: 11 \n**DENV-4 Placebo events: 1 TAK-003 events: 0 \nUnpublished data presented by Takeda to ACIP WG DENV-1   66.8% (37.4, 82.3%) VE in Seronegatives \n79\n.3% (63.5,  88.2%) \nDENV-1 78. 4%  (43.9, 91.7%) \n       \n  Hospitalization for DENV-3 and DENV-4 among seronegative \nchildren was low \n \n \n  Incidence \nde\nnsity/100 \nperson -years Incidence \ndensity/100 \nperson -years Placebo \nn =1832 TAK -003 \nn =3714 VE (95%  CI) \nDENV\n-1 14 0.17 6 0.03 78.4%  (43.9, 91.7%) \nDENV-2 23 0.28 0 0.0 100%  (NE, NE) \nDENV-3 3 0.04 11 0.07 –87.9%  (–573.4, 47.6%) \nDENV-4 1 0.01 0 0.0 100%  (NE, NE) \n \n    \n   \n    \n    \n   \n           \n   SS Suu umm mmm maa arr ryy y Summary: Hospitalizations \n• Seropositives \n• Protection against all 4 serotypes. \n• Few hospitalizations for DENV-4. \n• Seronegatives \n• Protection against DENV-1, and -2. \n• One hospitalization due to DENV-4. \n• No efficacy for DENV-3 \n• Data insufficient to rule out an increased risk of hospitalization among \nvaccinated children with DENV-3. \n   VE for Severe Dengue \n    \n \n                    \n           Vaccine Efficacy* Outcome: Dengue Hemorrhagic Fever \n(1997 Definition) \nOverall  VE \n70.0%  (31.5, 86.%) \nVE in Seropositives \n80.9%  (46.3, 93.2%) \nEvents  by Serotype \nPlacebo TAK-003 Events  by Serotype \nPlacebo TAK-003 VE in Seronegatives \n-3.4%  (-464.7,  81.1%) \nDENV-1 3 2 DENV-1 1 0 \nDENV-2 7 0 DENV-2 0 0 \nDENV-3 2 3 DENV-3 1 4 \nDENV-4 1 0 DENV-4 0 0 \nTotal 1  5 Total 2 4 \n*57 months after first dose, s ignificant results for vaccine efficacy bolded. Number for seropositive \nplacebo participants 4,855 and vaccine 9,666; Seronegative placebo 1,832 and vaccine 3,714. VE by serostatus from unpublished data from Takeda. \n   \n \n                    \n           Vaccine Efficacy* Outcome: Severe Dengue \nTrial-specific Definition \nOverall  VE \n70.2%  (-24.7,  92.9%) \nVE in Seropositives \n90.2%  (16.4,  98.9%) \nEvents  by Serotype \nPlac\nebo TAK-003 Events  by Serotype \nPlac\nebo TAK-003 VE in Seronegatives \n-999.0%  (NE,  NE) \nDENV-1 1 0 DENV-1 0 0 \nDENV-2 1 0 DENV-2 0 0 \nDENV-3 3 1 DENV-3 0 2 \nDENV-4 0 0 DENV-4 0 0 \nTotal 5 1 Total 0 2 \n*57 months after first dose, s ignificant results for vaccine efficacy bolded. Number for seropositive \nplacebo participants 4,855 and vaccine 9,666; Seronegative placebo 1,832 and vaccine 3,714. VE by serostatus from unpublished data from Takeda. \n  \n        \n       \n        \n        \n       SS Suu umm mmm maa arr ryy y Summary: Severe Dengue \n• Small number of events, difficult to stratify by serotype. \n• Seropositives: \n• Offered protection against dengue hemorrhagic fever and trial-\nspecific definition of severe dengue due to any serotype. \n• Seronegatives: \n• Few events. \n• No efficacy for dengue hemorrhagic fever and trial-specific definition of severe dengue due to any serotype. \n  Immunogenicity and Safety \n         \n   \n       \n            \n           \n     \n      \n     II Imm mmm muu unn noo ogg gee enn nii icc cii itt tyy y Immunogenicity \n• Subset of 2,518 TAK-003 and 1,247 placebo recipients (28% \nseronegative in each arm) \n• GMTs highest for DENV-2 serotype among TAK-003 recipients. \n• GMTs remained stable until 51 months after 1st dose for DENV-1, -3, and -4. \n• GMTs for DENV-2 decreased over time but remained higher than other \nserotypes at 51 months after 1st dose. \nGeometric mean titers (GMTs) calculated using PRNT50 \nSeropositivity = reciprocal neutralizing titers ≥10 \n    \n         \n    \n    \n        \n   \n   \n \n \n       VV Vaa acc ccc cii inn nee ess saa aff fee ett tyy y Vaccine safety \n• Solicited AEs were higher among recipients of TAK-003 compared to \nplacebo.* \n• Local: TAK-003 43%; placebo 26% \n• General: TAK-003 46%; placebo 40% \n• Unsolicited AEs were similar between recipients of TAK-003 and \nplacebo.* \n• Common TAK-003 unsolicited AEs: \n• injection site pruritus (0.7%) \n• bruising (0.6%) \n• pyrexia (0.2%) \n*Adverse events were analyzed using the safety set. \n                    \n          \n           \n    \n    \n     \n           \n    VV Vaa acc ccc cii inn nee ess saa aff fee ett tyy y:: :ss see err rii ioo ouu uss saa add dvv vee err rss see eee evv vee enn ntt tss s(( (SS SAA AEE E)) ) Vaccine safety: serious adverse events (SAE) \n• SAEs were similar among recipients of TAK-003 (8%) and placebo \n(10%). \n• 1 TAK-003 and 4 placebo recipients had SAEs related to the intervention \n• Common SAEs (>0.2%) among recipients included: \n• Dengue fever (TAK-003: 0.5%; placebo: 2%). \n• Dengue hemorrhagic fever (TAK-003: 0.1%; placebo 0.5%). \n• Incidence of death was 0.1% in both TAK-003 (n=16) and placebo \n(n=9) recipients. \n• No deaths attributed to TAK-003. \n  Summary \nFindings for TAK-003 \n•\n••\n•\n• P\nrotects seropositive recipients agains  t VCD  and  hospitalization  du e t o any serotype. \n Protects seronegative r ecipients agains  t VCD  and  hospitalization for  DENV-1 or DENV-2. \n Does  NOT protect  seronegative  recipients  agains  t VCD  an d hospitalization  for DENV-3. \n DENV-4 assessmen  t among  seronegativ  e children  is  limited  b y lo  w number   of events.  \n• No  protection  agains  t VCD  fo r DENV-4.   \n• Onl  y one  DENV-4  hospitalization  limits  efficac  y assessment. \n Unsolicited  , serious  advers  e events  , an  d deaths  similar  in  vaccin  e an  d placeb  o arms. \nSummary \nPending  Questions/Observations \n• \n•\n•  No efficacy  against  hospitalizations for DENV-3  among  seronegative vaccin  e recipients  \ncompared  t o placebo (-87.9%;  95  % CI  : -573.4–47.6%). \n• Dat  a insufficien  t t o rul  e ou  t  an increased  ris k among  vaccin  e recipients. Vaccin  e efficac  y agains  t hospitalizations  for  DENV-4  among  seronegative  recipients is \nunknown. \nUnclear  significanc  e  of immunogenicity  dat  a becaus  e no clearl  y define  d correlat  e  of \nimmun  e protecti  on exists. \n            \n \n \n \n   \n  \n   AA ACC CII IPP PDD Dee enn ngg guu uee eVV Vaa acc ccc cii inn nee ess sWW Woo orr rkk kgg grr roo ouu upp p ACIP Dengue Vaccines Workgroup \nACIP Members \nWilbu  r Che  n (Chair) \nKathy  Poehling \nBeth  Bell \nVeronic  a McNally \nCD C Co-Lead \nG\nabriela Paz-Bailey \nLaura Adams \nEx Officio Members \nKaitly  n Morabit  o (NIH) \nRalp  h LeBlan  c (FDA) \nIhid Carneir  o Lea  o (FDA) \nKir k Prutzma  n (FDA) \nSrihar  i Seshadri (DOD) L iaison Representatives \nElizabeth Barnett (AAP) \nRob Schechter (AIM) \nConsultants \nEdwin  Asturias \nRobert  Atmar \nAlan  Barrett \nIris  Cardona \nAnn  a Durbin \nTony  Marfin \nKristen  Pierce \nAnit  a Shet C DC Contributors \nJosh  Wong \nMim  i Eckert \nRache  l Eidex \nAlfonso  Hernandez \nSusan  Hills \nTerri Hyde \nMike  McNeil \nJorge  Munoz \nErin  Staples \nCindy  Weinbaum \nRita  Helfand", "summary": "WW Woo orr rkk kGG Grr roo ouu upp pSS Suu umm mmm maa arr ryy yaa ann ndd d II Inn ntt tee err rpp prr ree ett taa att tii ioo onn noo off fTT TAA AKK K-- -00 000 033 3EE Eff fff fii icc caa acc cyy y,, , SS Saa aff fee ett tyy y,, ,aa ann ndd dII Imm mmm muu unn noo ogg gee enn nii icc cii itt tyy yDD Daa att taa aWork Group Summary and  Interpretation of TAK-003 Efficacy,  Safety, and Immunogenicity Data  Gabriela Paz-Bailey, MD, PhD, MSc  Dengue Branch Chief  Division of Vector Borne…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/Dengue-03-Paz-Bailey-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 22}
{"title": "Varicella 01 Marin 508", "content": "National  Center  for Immunization  & Respiratory  Diseases \nDivision  of Viral  Diseases \n25 Years of Varicella Vaccination Program in the United States: \nHealth and Economic Impact during 1995–2019 \nMona Marin, MD \nCenters for Disease Control and Prevention, Atlanta, GA \nAdvisory Committee on Immunization Practices \nAtlanta, GA \nFebruary 23, 2023 \n         \n          \n \n          \n         \n \n                   Varicella: from rite of passage to vaccine- preventable disease. \n Historically, varicella was considered disease of little consequence, too mild to \nwarrant prevention \n Mid-1950s: first reported fatal varicella cases in children treated with newly introduced immunosuppressive therapy unmasked the lethal potential of the varicella-zoster virus (VZV)\n1 \nChild with leukemia who died of varicella, ~1970 (courtesy of Dr. Anne Gershon) \n1Cheatham et al. Am J Pathol 1956; 32:1015-35. 2 \n                                                  Varicella: from rite of passage to vaccine- preventable disease. \nIatrogenic  immunosuppression  : \nsystemic  steroid  therapy, organ  \ntransplant, childhood  cancer US trial  s in children  with  leukemi  a \ndemonstrated  vaccine  efficacy  and  \nsafety2 \n• Leukemia  cured  in 80%  of childre  n \nbut many  died  of varicell  a before  \nimmune  reconstitution •  Subsequent  studies  showe  d \nsafety  and efficacy  in healthy  \nchildren  and adults 1974 1995 \nVaricell  a vaccine  (Japan), VZV  \nattenuated, healthy  children  and  \nadults  and children  with  \nleukemi  a in remission1 \n• Initia  l controversy  in the U.S.  : \nrisk for latency  an d \npersistence  of immunit  y Varicell  a vaccine  licensed  in  \nthe U.S . \n• First  country  with  a routine  \nvaricell  a vaccinatio  n \nprogram 1960s/70s 1980s \nGershon at al. JID 2021. Marin et al. JID 2022. In press. 1Takahashi et al. Lancet 1974 2Gershon et al. JAMA 1984. 3 \nDebate  around  t he \ntime   of varicell  a \nvaccine  \nrecommendatio nsDoes  the health  \nburden  o f \nvaricella  justify   a \nvaccination  \nprogram? \nWould  th e \nvaricell  a \nprogram  shif  t \nburden  fro  m \nchildren  to  \nadults? \nWould  th e \nvaccine  b e \naccepted  b y \nparents  and  \nproviders? \nWould  th e \nvaricella  progra  m \nincrease  H Z \nincidence? \n4 \nU.S. Varicella  Vaccination Program\n\n       \n        \n  \n \n   \n    \n     \n                       \nBefore vaccine, varicella represented a significant health \nburden (medical and societal) in the United States. \nAnnual average, pre-vaccine \n Cases ~4 million \n Hospitalizations ~10,500–13,500 \n Deaths ~100–150 \n Congenital varicella syndrome ~44 \n Greatest disease burden in children \n– >90% cases, 70% hospitalizations, 50% deaths \nWharton et al. 1996, Galil et al. 2001, Davis et al. 2004, Meyer et al. 2000, Nguyen et al. 2005, Enders and Miller. 2000 6 \n      \n   \n        \n    \n       \n      \n    \n    \n       \n \n      \n  \n       Varicella vaccine policy in the United States \n 1995: Routine one-dose \n– \n–  \n \n– \n– \n– \n– O ne dose routinely at age 12–18 months with \ncatch-up vaccination of older children R\nationale for policy change \nTwo doses for susceptible persons aged ≥13 years Low-level  community  \ntransmission  continued \n 2007: Policy changed to routine 2-dose Outbreaks  in highly  1-\ndose  vaccinated  school  \npopulations  (smaller  , \nless frequent) 1st dose at age 12–15 months \n2nd dose at age 4–6 years \nCatch-up vaccination of persons who had received \none dose \nVaccination of all eligible persons without \nevidence of immunity \nMMWR 2007;56(RR-4):1–39. Available at www.cdc.gov 7 \n     100% \n90% \nAverage 2-dose \nvaricella Average 2-dose \nMMR \n2006 2008 2010 2012 2014 2016 2018 2020 80% Percent Vaccinated 70% \n60% 50% 40% \n30% \n20% \n10% \n0% \nYear \n8        100 \n90 \n≥ 1 dose \n80 MMR ≥ 1 dose Percent Vaccinated varicella 70 \n60 \n50 40 \n30 \n10 20 \n1996 2000 2004 2008 2012 2016 2020 \nYear 0 \n        Program implementation was highly successful. \nVaccination  coverage  for ≥1 dose  varicell  a \nand ≥1 dose MMR,  children  age 19–35  \nmonths,  US 1996–2020 \nData  Source:  National  Immunization  Survey Vaccination  coverage  for ≥2 doses  varicell  a \nand ≥2 doses  MMR,  children  by age 7  \nyears  — 6 US states,  2006–2020 \nData  Source:  Immunization  Information  System \nElam-Evans et al. JID 2022. \n    \n     \n                            \n               \n   \n  \n \n \n Post-licensure vaccine effectiveness among children \nVaricella Endpoint 1 dose VE 2 dose VE \nVaricella of any \nseverity 82% \n(Meta-analysis) 92% \n(Meta-analysis) \nModerate and Severe disease 97% \n(Median) \nSevere* disease 100% \n(range= 97-100) \nHIV+ children (2 doses, 1 study)- 82% (95% CI 24%–100%)1 \n*Definitions: 1) Varicella with >500 lesions or a complication requiring physician visit; 2) disease severity scale used in clinical \ntrials: # lesions, fever, systemic signs and subjective assessment of illness \nMarin et al. Pediatrics 2016. 1Son et al. JID 2010. 9 \nImpact  of 25  Years  of the U.S. Varicella Vaccination  \nProgram  on Varicella \n\n   \n              \n     Varicella incidence* declined >97%, 1990–2019. \n*4 states with consistent reporting of cases to the National Notifiable Diseases Surveillance System. \nMarin et al. JID, 2022. 11 \n         \n   \n  0 50 100 150 200 250 Incidence per 100,000 \npopulation 2005-2006 \n2018-2019 \n-76% -18% -15% -64% -92% -95% -74% \n<1 1–4 5–9 10–14 15–19 20-29 ≥30 \nAge group (years) \n                  \n              \n                    Varicella incidence declined in all age groups during the \n2-dose program*. \nIn 7 states with consistent reporting, the number of outbreaks declined 82%§ \n*29 states and the District of Columbia reported age data during 2005–2006 (end of 1-dose program) and 38 during 2018–2019 \n(mature 2-dose program); National Notifiable Diseases Surveillance System data; Marin et al. JID 2022. \n§Outbreak: ≥5 varicella cases; Leung et al. JID 2022. 12 \nVaricella hospitalizations declined 90% during 1993–2019. \n     \n            Marin et al. JID 2022. Data: HCUP National Inpatient Sample (NIS). 13 \n      \n   \n                     \n \n >10,500 hospitalizations are prevented now annually, \nincluding >1,250 among infants. \nAge Group Average annual no. \nhospitalizations \n1993-95 Average annual no. \nhospitalizations \n2018-19 Decline in \nhospitalization rate \n<1 1,338 55 -96% \n1-4 4,309 80 -98% \n<20 8,574 285 -97% \n<50 11,573 783 -94% \nAll ages 12,189 1,390 -90% \nMarin et al. JID 2022. Data: HCUP National Inpatient Sample (NIS). 14 \n            \n          \n        Varicella mortality declined 89% during 1990–2019. \nMost of the decline occurred during the 1-dose program. \nVaricella as the underlying cause of death. National Center for Health Statistics data. \nMarin et al. JID 2022. 15 \n    \n                    \n   \n        \n        \n      Deaths practically eliminated among <20-year-olds. \nDeaths with varicella as the underlying cause, \npersons aged <50 years-old, 1990-2019 \n0 20 40 60 80 100 120 20-49 yrs (94% reduction) \n<20 yrs (99.4% reduction) Number of deaths \nYear \nNo varicella deaths (underlying or contributing) reported in the <20 years age group in 2011, 2013, 2014, 2017, 2018. Data: National \nCenter for Health Statistics Marin et al. JID 2022. \n16 \nHerpes  Zoster  Trends  During  the U.S. Varicell  a \nVaccination  Program  \n\n         \n         \n          In persons aged ≥30 years, HZ incidence increased during \nthe earlier study years, with decelerations in later years. \n30-39 40-49 50-59 60-69 ≥70 \nTotal \n0.0 2.0 4.0 6.0 8.0 10.0 12.0 HZ Incidence per 1000 Persons \nYear \nLeung et al. JID 2022. MarketScan 1998–2019. 18 \n          \n         \n      \n              \n  \n    \n  In children and young adults, HZ incidence declined in a \nstep-wise pattern once each age group was comprised by persons born during the varicella vaccination program. \nHZ incidence before opportunity \nfor routine varicella vaccination HZ incidence after opportunity for routine varicella vaccination \n1-4 5-9 10-14 15-19 20-24 \n0 1 2 3 HZ Incidence per 1000 Persons \nYear \nLeung et al. JID 2022. MarketScan 1998–2019. 19 \n        \n        US varicella vaccination resulted in substantial disease prevention \nand societal savings over 25 years of program implementation. \n20 Effective,  safe,  and  \naccepted  vaccine \nHigh  vaccin  e \ncoverage  reached Prevented  morbidity &  \nmortality \n91 million  cases  \n238,000  hospitalizations \n1,933-2,446  deaths Highly  cost saving \n$23.  4 \nbillion \nin ne t \nsocietal  savings No increase  in HZ due  \nto varicella program \nReduced  HZ incidence  i n \nchildren/adolescents \n\n     \n     \n    \n      \n  \nThe varicella vaccination \nprogram in the US: 25 years of saving lives and preventing illness \nThe Journal of Infectious Diseases supplement \nNovember 1st, 2022 \nhttps://academic.oup.com/jid/issue/226/Supplement_4 \n21 \n \n \n \n      \n    \n         Acknowledgements \nCo-authors \n \n \n \n \n \n \n  \n \n   \n \n  \n \n  \n \n  Jessica  Leung \nKathleen  Dooling \nTara  Anderson \nAdriana  Lopez \nMichael  Melgar \nAaron  Curns \nFangjun  Zhou \nN\nurses, physicians, pharmacists \nState and local health department staff \nVaricella active surveillance project staff \nCDC Division of Viral Diseases past/present staff JID supplement contributors \nJane  Seward \nAnne  Gershon \nLaurie  D. Elam-Evans \nEugene  Shapiro \nSheila  Dollard \nAnn Arvin \nMarci  Drees \nIsmael  Ortega-Sanchez \nRafael  Harpaz \nAlexandra  Hess \nLauren  Pearson \nOlga  Munteanu \nJanine  Cory \nNina  Masters \n    \n \n      \n                  \n          Thank You \nFor more information, contact CDC \n1-800-CDC-INFO (232-4636) TTY: 1-888-232-6348 www.cdc.gov \nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.", "summary": "National  Center  for Immunization  & Respiratory  Diseases  Division  of Viral  Diseases  25 Years of Varicella Vaccination Program in the United States:  Health and Economic Impact during 1995–2019  Mona Marin, MD  Centers for Disease Control and Prevention, Atlanta, GA  Advisory Committee on Immunization Practices  Atlanta, GA  February 23, 2023                                                                   Varicella: from rite of passage to vaccine- preventable disease.   Historically,…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/Varicella-01-Marin-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 23}
{"title": "COVID 01 Daley 508", "content": "cdc.gov/coronavirus\nACIP COVID-19 Vaccines Work Group\nDr. Matthew F. Daley, Work Group Chair\nFebruary 24, 2023\nDecember 8, 2022: FDA1granted emergency use authorization (EUA) for:\n–\n–Use of Moderna bivalent COVID- 19 vaccine booster in children ages 6 months -5 years \nUse of Pfizer- B ioNTech bivalent COVID- 19 vaccine as a third primary series dose for \nchildren 6 months- 4 years of age\nDecember 9, 2022: CDC2expanded the use of updated (bivalent) COVID- 19 \nvaccines for children 6 months through 5 yearsCOVID-19 vaccine update:\nBivalent booster authorizations extended to children ages 6 months and older\n21. https://www.fda.gov/news- events/press-announcements/coronavirus- covid -19-update- fda-authorizes-updated-bivalent- covid -19-vaccine s-children- down -6-months\n2. https://www.cdc.gov/media/releases/2022/s1209- covid -vaccine.html\nEpidemiology of COVID- 1 9, including MIS- C and hospitalization data \nVaccine effectiveness (VE) updates\nCOVID -19 a mong persons with immunocompromise, including VE and Evusheld updates \nDiscussions for inputs on cost effectiveness analyses \nCOVID -19 v accine safety updates \nReview benefit/risk analysis\nUpdates to COVID- 19 vaccines in children 6 months through 5 years of age, including \nModerna COVID-19 vaccine booster doses \nOngoing work to increase uptake of bivalent COVID- 19 v accines\nConsiderations for transition to bivalent primary series\nFuture directions for COVID- 19 v accines  ACIP COVID-19 Work Group Meeting Review\nOctober 2022– February 2023\n3\nCOVID- 19 v accine safety updates: CDC Dr. Shimabukuro (CDC)\nCOVID- 19 v accine safety update: FDA Dr. Forshee (FDA)\nVaST su mmary Dr. Talbot (ACIP , VaST )\nWork Group interpretation and summary Dr . Twentyman (CDC)\nBreak\nUpdates on COVID -19 ho spitalizations in the US Dr. Taylor (CDC)\nUpdates to COVID -19 v accine effectiveness in the US Dr. Britton (CDC)\nConsiderations for transitioning to bivalent primary series Dr . Oliver (CDC)\nWork Group interpretation and summary Dr . Twentyman (CDC)\nDiscussion\nBreak\nBenefit- r isk analysis for COVID -19 vaccines Dr. Wallace (CDC)\nCOVID-19 vaccines: future directions Dr. Oliver (CDC)\nDiscussionAgenda: Friday February 24, 2023\nACIP members\nMatthew Daley (ch air)\nBeth Bell \nGrace Lee\nKeipp Talbot\nOliver Brooks\nEx-o\nfficio/government members\nFDA: Rachel Zhang, Lucia Lee, Anuja Rastogi\nNIH: Chris Roberts\nIHS: Uzo Chukwuma\nCMS: Jeff Kelman\nBARDA: Christine Oshansky\nHHS: David Kim\nCDC: Alan Lam\nCDC L\neads\nSara Oliver\nEvelyn TwentymanWork Group members\n5LiaisonsAAFP: Jonathan Temte\nAAP: Sean O’Leary\nACOG: Denise Jamieson (primary), \nLa\nura Riley (alternate)\nACP: Jason Goldman\nADS: Emily Kahn\nAGS: Ken Schmader\nAIM: Rob Shechter (primary), J\nane Zucker (alternate)\nAMA: Sandra Fryhofer\nANA: Ruth Francis (alternate)\nAPhA: Michael Hogue\nASTHO: Marcus Plescia\nCSTE: Susan Lett, Paul Cieslak, Christine Ha\nhn\nIDSA: Jeff Duchin (primary)Liaisons, cont’d\n\n\n\n\nNACCHO: Matt Zahn (primary), \nJeff Duchin (alternate)\nNACI: Matthew Tunis (primary),\nNicole Forbes (alternate)\nNFID: Bill Schaffner (primary), Marla Dalton (alternate)\nNMA: Patricia Whitley -Williams\nSHEA: Marci Drees,\nPreeti Mehrotra (alternate) \nC\nonsultants\n\nEd Belongia\nKathy Kinlaw \nDayna Matthew \nKathleen N euzil\nStanley Perlman \nPeter S zilagyi\nHank Bernstein\nSarah Meyer\nElisha Hall\nMegan Wallace\nDanielle Moulia\nLauren Roper\nHannah Rosenblum\nKatherine Fleming -D utra\nMonica Godfrey\nSusan Goldstein\nMary Chamberland\nStephen Hadler\nJoEllen Wolicki\nMelinda Wharton\nJessica MacNeil\nAmanda CohnCDC participants\n6Ruth Link -Gel les\nAmadea Britton\nCarolyn Bridges\nAllison Ciesla \nNicole Dowling\nAshley Fowlkes\nHeather Scobie\nNatalie Thornburg\nTom Shimabukuro\nJohn Su\nJulianne Gee\nKaren Broder\nRita Helfand\nJefferson Jones\nYvonne BolenIsmael Ortega- San chez\nPragna Patel \nAmanda Payne\nGeorgina Peacock\nJose Romero\nLaura Steinhardt\nRyan Wiegand\nPatricia Yu\nYon YuSamuel Graitcer\nLisa Grohskopf\nKatherine Grusich\nAaron Hall\nEbony Houston\nTerri Hyde\nCynthia Jorgensen\nKristen Nordlund\nSierra Scarbrough\nEdwin Shanley\nAndrew Kroger\nLauri Markowitz\nNoelle -An gelique Molinari\nMichael McNeil\nMorgan Najdowski\nFor more information, contact CDC\n1-800-CDC- INFO (232- 4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.\nThank you!", "summary": "cdc.gov/coronavirus ACIP COVID-19 Vaccines Work Group Dr. Matthew F. Daley, Work Group Chair February 24, 2023 December 8, 2022: FDA1granted emergency use authorization (EUA) for: – –Use of Moderna bivalent COVID- 19 vaccine booster in children ages 6 months -5 years  Use of Pfizer- B ioNTech bivalent COVID- 19 vaccine as a third primary series dose for  children 6 months- 4 years of age December 9, 2022: CDC2expanded the use of updated (bivalent) COVID- 19  vaccines for children 6 months…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/COVID-01-Daley-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 7}
{"title": "COVID 02 Shimabukuro 508", "content": "National Center for Emerging and Zoonotic Infectious Diseases\nCOVID-19 mRNA bivalent booster vaccine safety\nAdvisory Committee on Immunization Practices (ACIP) meeting\nFebruary 24, 2023\nTom T. Shimabukuro, MD, MPH, MBA\nDirector, Immunization Safety Office\nDivision of Healthcare Quality Promotion Centers for Disease Control and Prevention (CDC)\n\nTopics\nDescribe CDC’s Vaccine  Safety Datalink (VSD) Rapid Cycle Analysis (RCA) \nm\nonitoring methods and assessment processes for statistical signals\nDescribe VSD RCA signal detection and signal assessment for ischemic s\ntroke after Pfizer -BioNTech COVID -19 mRNA bivalent booster dose \nvaccination in the age group 65 years and older\nDescribe rates of myocarditis/pericarditis following COVID-19 mRNA v\naccination\n2\nBackground: COVID -19 mRNA bivalent booster \nvaccination in the United States\nBivalent COVID -19 mRNA booster vaccinations first became available in the\nUnited States in September 2022\nAs of February 8, 2023, 52.5 million COVID -19 m RNA bivalent booster doses\nadministered in people ages 5 years and older in the United States*\n•Includes 22.3 million doses in people ages 65 years and older*\nCDC and partners monitor the safety of licensed and authorized U.S. vaccines\nus\ning multiple complementary systems (Vaccine Information and Safety Studies | Vaccine Safety | CDC )\nSafety data support CDC recommendations that everyone eligible for a COVID -\n19 mR\nNA bivalent booster get vaccinated\n3 *CDC COVID Data Tracker: Vaccinations in the US\nVSD COVID-19 Rapid Cycle Analysis: \nPreliminary Analyses of Ischemic Stroke after \nPfizer-BioNTech Bivalent Booster Dose\nPrepared by:\nKaiser Permanente Northern California Vaccine Study Center\nPresented by Tom Shimabukuro, MD, MPH, MBA\nCenters for Disease Control and Prevention\n4\nVaccine Safety Datalink (VSD)\nEstablished in 1990\nCollaborative project between CDC and 9 integrated healthcare organizations\nIncludes electronic health record data on ~12.5 million individuals across all sites 5\nStrengths of VSD Rapid Cycle Analysis (RCA)\nPopulation\n•~12.5 million people (equal to ~4% of the U.S. population) across VSD data sites are\nge\nographically and racially/ethnically diverse\nData\n•Near real -time data, with analyses updated weekly\n•A\nccess to comprehensive medical records, including exposures (vaccination) and outcomes,\nallo\nwing rapid chart reviews to obtain additional clinical information as needed\nInnovative Methods\n•Vaccinated concurrent comparators : Re cent vaccinees as comparators are expected to be more\nsimilar to current vaccinees than unvaccinated individuals with the following advantages\n‒\n‒Careful adjustment for potential biases associated with calendar time, site, and demographic factors A\nnalyses can begin sooner than alternative methods \n•Supplemental analyses conducted weekly: Un vaccinated/un- boosted comparators would also be\navailable to provide context in real time\n•Using vaccinated concurrent comparators with supplemental analyses offers substantial benefits\nco\nmpared with either unvaccinated or historical comparators\n6\nVSD RCA for bivalent boosters\nPre-specified outcomes were assessed during weekly sequential\nmon\nitoring after COVID-19 bivalent booster vaccination*\n•Risk of pre-specified outcomes 1– 21 day s following a bivalent vaccination\ncompared with bivalent vaccinated individuals who were 22– 42 days\nfollowing the bivalent dose\n•All analyses adjusted for age, sex, race/ethnicity, VSD site, calendar time\n(day\ns) and seasonality (time)\n•Signal if p-value <0.01 (1-sided)\n* Rapid Cycle Analysis (RCA) to monitor the safety of COVID -19 vaccines in near real -time within the Vaccine Safety Datalink. Av ailable at:\nRapid Cycle Analysis (RCA) to monitor the safety of COVID -19 vaccines in near real -time within the Vaccine Safety Datalink (cdc. gov) 7\nVaccinee with outcome in the risk interval and a concurrent comparator\n“bivalent vaccinated individuals only”\nOn each calendar day that an outcome \noccurred in a vaccinee (e.g., October 3), w e \ncompared vaccinees in their risk interval (day 1–21) with similar vaccinees in their \ncomparison interval (day 22–42)\nBy similar, we mean that on the same calendar \nday, they were in the same age group and of the same sex, race/ethnicity, and at the same VSD site\nComparison Interval 22– 42 days post -vaccination 42 22 October 3\nVaccinated with \nBivalent Booster \nSeptember 31\nRisk Interval 1 –21 days post -vaccination21October 3\nVaccinated with \nBivalent Booster \nSeptember 30\n8\n9VSD COVID-19 vaccine RCA prespecified surveillance outcomes\nPrespecified outcomes Settings\nAcute disseminated encephalomyelitis Emergency dept, Inpatient\nAcute myocardial infarction Emergency dept, Inpatient\nAcute respiratory distress syndrome Emergency dept, Inpatient\nAnaphylaxis* Emergency dept, Inpatient\nAppendicitis Emergency dept, Inpatient\nBell’s palsy Emergency dept, Inpatient, Outpatient\nCerebral venous sinus thrombosis Emergency dept, Inpatient\nDisseminated intravascular coagulation Emergency dept, Inpatient\nEncephalitis / myelitis / encephalomyelitis Emergency dept, Inpatient\nGuillain -Barré syndrome Emergency dept, Inpatient\nImmune thrombocytopenia Emergency dept, Inpatient, Outpatient\nKawasaki disease Emergency dept, Inpatient\nMultisystem inflammatory syndrome in children/adults (MIS -C/MIS- A) Emergency dept, Inpatient\nMyocarditis / pericarditis * Emergency dept, Inpatient\nNarcolepsy / cataplexy Emergency dept, Inpatient, Outpatient\nPulmonary embolism Emergency dept, Inpatient\nSeizures/Convulsions (including 0- 7 days for youngest ages) Emergency dept, Inpatient\nStroke, hemorrhagic Emergency dept, Inpatient\nStroke, ischemic Emergency dept, Inpatient\nThrombosis with thrombocytopenia syndrome Emergency dept, Inpatient\nThrombotic thrombocytopenic purpura Emergency dept, Inpatient\nTransverse myelitis Emergency dept, Inpatient\nVenous thromboembolism Emergency dept, Inpatient, Outpatient\n*All outcomes are first ever in the ICD -10 era, except anaphylaxis which is first in 7 days, and myocarditis/pericarditis which is first in 60 daysIn COVID- 1 9 bivalent booster vaccine monitoring, VSD RCA detected a statistical signal for ischemic stroke after \nPfizer -BioNTech bivalent booster vaccination in the age group 65 years and older\nNo other VSD RCA pre- s pecified surveillance outcomes have signaled in any age groups for either of the mRNA \nCOVID -19 bivalent booster vaccines or when data for the two mRNA vaccine types are combined/pooled\nVSD investigations of an RCA signal to assess whether it \nreflects a real effect of vaccination on an outcome\nData quality assessment for errors, anomalies, or missing/late-arriving data\nAnalyses using different comparators than primary concurrent (e.g., un-boosted, \nunv\naccinated or “historical” comparators) to supplement our primary analyses\nAdditional investigations to provide context (e.g., background rates, etc.)\nGraphic displays of outcome incidence day by day after vaccination, using temporal scan s\ntatistics to assess apparent clustering\n•Examine the temporal clustering of outcome events in subgroups defined by demographics, site or \nsi\nmultaneous exposure (e.g., flu vaccine)\nIf the signal is driven by a strong association in one subgroup or VSD site, further \nanal\nyses by site or subgroup as appropriate\nChart review to confirm cases and collect additional data (e.g., date of symptom onset). \nConsider epidemiologic studies to further investigate surveillance findings\n10R\napid Cycle Analysis (RCA) to monitor the safety of COVID -19 vaccines in near real -time within the Vaccine Safety Datalink. Avai lable at: Rapid \nCycle Analysis (RCA) to monitor the safety of COVID -19 vaccines in near real -time within the Vaccine Safety Datalink (cdc.gov)\nVSD COVID -19 RCA preliminary analyses: \nIschemic stroke after Pfizer- BioNTech bivalent \nbooster among people ≥65 years of age\n11\nNumber of COVID-19 bivalent booster doses and influenza vaccine doses \nadministered over time among persons aged ≥65 years, by vaccine type in VSD\n12\nVSD RCA Ischemic Stroke Definition\nICD-10 CODES TO FIND INCIDENT \nCASES  ICD-10 CODES FOR LOOKBACK TO ADJUST \nONSET DATE  (in all settings)ICD-10 CODES -TO DETECT PREVALENCE \n(history of, in all settings)                         ICD-10 CODES -OTHER CAUSE EXCLUSIONS (in all settings) \nStroke, ischemic  \n(settings = Emergency, Inpatient)Codes to adjust Stroke, ischemic onset \n(if seen within 1 day before case)Stroke, ischemic - Review for Prevalence -1ST EVER Other possible causes of Stroke, ischemic\nG45.8 Other transient cerebral \nischemic attacks and related syndromes\nAdjust onset date if occurs in the 1 day prior to \nincident case:Exclude if occurs EVER prior to incident case:Exclude if COVID -19 in the last 30 days prior to incident case (not \nincluding same day): \nG45.9 Transient cerebral ischemic attack, unspecifiedCOVID -19 DIAGNOSIS \nI63.* Cerebral infarction Z92.82 Status post administration of tPA\n(rtPA ) in a different facility within \nthe last 24 hours prior to admission to current facilityZ86.73 Personal history of transient ischemic attack (TIA), and cerebral infarction without residual deficitsOR\nCOVID -19 POSITIVE LAB TEST\nR51.* Headache I69.* Sequelae of cerebrovascular disease Exclude if occurs in the time period noted prior to incident case (not including same day):\nR47.* Speech disturbances, not elsewhere classified I48.*Atrial fibrillation and flutter (if seen EVER prior to incident case)\nR29.810 Facial weakness I21.* Acute myocardial infarction  (if seen within 28 days prior to incident case)\nR53.1 Weakness\nS15.*Injury of blood vessels at neck level (if seen within 1 day prior to incident case)\nR42.* Dizziness and giddiness\nI74.*Arterial embolism and thrombosis (if seen within 1 day prior to incident case)\nR41.82 Altered mental status, unspecified D57.* Sickle -cell disorders (if seen EVER prior to incident case)\nR40.4 Transient alternation of awareness\nD68.5*Primary thrombophilia (if seen EVER prior to incident case)\nG81.9* Hemiplegia, unspecified\nH53.9 Unspecified visual disturbance\nH53.13* Sudden visual loss\n13\nBivalent RCA concurrent comparator analyses of\nischemic strokes during a 1–21-day Risk Interval versus \na 22–42- day Comparison Interval*\nNominal analysis Sequential analysis\nAge group \n(years)VaccineRisk \nevents (N)Comp \nevents (N)Adjusted \nRate Ratio95% \nConfidence \nInterval1-sided\np-valueSignal? \n1-sided\np <0.01\n18–64Pfizer 39 38 1.09 0.68 – 1.75 0.398 No\nModerna 14 26 0.49 0.24 – 0.95 0.990 No\n65+ Pfizer 143 117 1.36 1.05 –1.76 0.011 No\nModerna 68 63 1.17 0.82 – 1.67 0.224 No\n*Data through Feb 4, 2023\n14\nIschemic stroke after Pfizer -BioNTech bivalent booster, age ≥65 \nyears, counts and adjusted rate ratios (Oct 16, 2022 –Feb 4 , 2023 )\n1503.954.38\n1.51\n1.251.491.92 1.85 1.89\n1.571.531.54 1.471.461.36 1.39\n00.511.522.533.544.55\n020406080100120140160\nRate RatioNumber of Cases in Risk or Comp Window\n1-21 Day Risk Interval 22-42 Day Comp Interval Rate RatioRR = 1.36 (95% CI 1.05-1.76)\nRed dot represents sequential signal: p- value <0.01 (1-sided)\nIschemic stroke by day after Pfizer -BioNTech bivalent \nboosters, people ages ≥65 Years*\n*Data cutoff 3 weeks priorSignificant cluster days 13– 22, \np-value = 0.0150\n16\nIschemic stroke preliminary chart review: Cases ≥65years old during \ndays 11–21 post- Pfizer -BioNTech bivalent booster vaccination\nReview of a subset of cases at one site (N=24); 22 of 24 were incident stroke/TIA (pos. pred. value 92%)\n•None had any history of stroke or transient ischemic attack (TIA)\n•Median age of verified cases was 77.5 years\n•Symptom onset date rarely shifted from electronic date\n•5 (23%) with known history of SARS -CoV-2 infection, only 1 within last 6 months \n•0 with mention of recent exposure to SARS -CoV-2 in chart notes\n•14 (64%) had simultaneous flu vaccination on the same day (13 high- dose flu vaccines and 1 adjuvanted flu vaccine)\nOutcomes\n•13 of 22 (59%) discharged home\n•4 of 22 (18%) discharged home with home health \n•2 of 22 (9%) discharged to a skilled nursing facility\n•3 of 22 (14%) died \n‒One death in a 75– 79-year-old male ~1 month after stroke; death was likely related to the stroke\n‒One stroke in a 65– 69-year-old female noted after craniotomy, though relationship with surgery unclear; death due \nto cardiac arrest ~2.5 months later\n‒One stroke in a 70– 74-year-old male during hospitalization for metastatic cancer, with subsequent death due to \ncancer -related complications during hospitalization\nCurrently reviewing a random sample of risk and comparison interval cases across VSD sites 17\nAge group \n(years)Interval \n(days)Comparators VaccineRisk\nevents (N)Comp\nevents (N)Adjusted \nRate Ratio95% \nConfidence \nIntervalP-value\n(2-sided)\n65+ 1–21Not bivalent\nboostedPfizer 134 1510 1.07 0.89– 1.28 0.483\n* Analyses only included outcomes through December 10, 2022. \n18Supplemental analyses:\nIschemic strokes during the 1–21-day interval comparing bivalent boosted \nvs. un -boosted concurrent comparators (but eligible for bivalent booster )*\nAge group\n(years)Interval\n(days)Comparators VaccineRisk \nevents (N)Comp \nevents (N)Adjusted \nRate Ratio95%\nConfidence\nIntervalP-value\n(2-sided)\n65+1–21Not bivalent\nboostedPfizer 134 1510 1.07 0.89– 1.28 0.483\n22–42Not bivalent\nboostedPfizer 83 1081 0.76 0.60– 0.95 0.018\n* Analyses only included outcomes through December 10, 2022. \n19Findings suggest reduced rate of stroke in comparison intervalSupplemental analyses:\nIschemic strokes during the 1– 21 and 22–42 -day interval comparing bivalent \nboosted vs. un- boosted concurrent comparators (but eligible for bivalent booster )*\nPost-signal analyses:\nSimultaneous high -dose or adjuvanted influenza vaccines\n20\nAnalytic populationCases in 1– 21-day\nRisk Interval\n(N=139)Cases in 22–42-day\nComparison Interval\n(N=108)Adjusted\nRate Ratio**\n(95% CI)P-value \nBivalent Pfizer + same- day\nhigh- dose or adjuvanted flu \nvaccine43 26 1.65 (1.02 –2.72) 0.04\nBivalent Pfizer + same day\nstandard dose flu vaccine8 8 1.00 (0.36 –2.76) 1.00\nBivalent Pfizer without anysame day flu vaccine88 74 1.19 (0.87 –1.62) 0.27\n21* Analyses only include vaccination data through December 3, 2022, and stroke outcome data through January 14, 2023\n** Adjusted by 5- year age groupsPost -signal analyses*:\nIschemic stroke incidence during days 1–21 compared with days 22–42, \namong ≥65 years with and without simultaneous influenza vaccination\nPost -signal analyses*: \nExpected cases after bivalent booster + high -dose or adjuvanted flu vaccine, \nbased on ischemic stroke incidence in un-boosted people eligible for a booster\nAge at\nvaccinationExpected cases in a \n3-week interval \n(Risk or Comparison)Observed cases\nin a 1 –21-day\nRisk Interval (N)Observed cases \nin 22 –42-day \nComparison Interval (N)\n65–69 years 7.3 8 6\n70–74 years 8.5 8 7\n75–79 years 9.8 11 6\n80–84 years 6.3 8 3\n85–89 years 4.2 5 4\n90+ years 2.5 3 0\nTotal 38.7 43 26\n*Analyses only include vaccination data through December 3, 2022, and stroke outcome data through January 14, 2023\n22Findings also suggest reduced rate of stroke in comparison interval\nIschemic stroke following bivalent Pfizer -BioNTech COVID-19 \nmRNA booster vaccination in people ages 65+ years\nStatistical signal persistent for 8 weeks\n•Rate ratio has slowly attenuated from 1.92 to 1.36 and intermittently met signaling\nc\nriteria\nAdditional signal investigation analyses\n•Temporal clustering evaluation found a significant cluster 13–22 days after vaccination\n•Supplemental analyses using un- boost ed concurrent comparators showed a rate ratio\nRR=1.07 (95% CI 0.89–1.28)\n•Of small subset of charts reviewed, most confirmed cases had simultaneous high-doseor\n adjuvanted flu vaccine\n•Analyses evaluating simultaneous high- dose or adjuvanted flu vaccine showed a rate\nratio RR=1.65 (95% CI 1.02–2.72; p- value 0.04)\n‒Separate analyses did not detect an elevated RR for stroke after flu vaccine alone (data not shown)\n•Supplemental analyses suggest comparison interval (22–42 days) rates were lowert\nhan expected\n23\nAdditional considerations\nSmall numbers of strokes and imprecise rate ratios limit some analyses \n•Reduced follow -up time after Moderna booster due to distribution delays\n•Simultaneous flu vaccine analyses limited by small numbers\nDifficult to interpret temporal clustering during risk and comparison intervals\nPossible unmeasured confounding \n•Results may be influenced by confounders that vary over time\n•Do early adopters of bivalent booster vaccine have greater risk of near- term cardiovascular events? \n‒Same trend has not been observed for acute myocardial infarctions \n‒Potential impact of differential vaccine availability after EUA (Pfizer -BioNTech > Moderna)\nPossible role of SARS -CoV -2 infection before booster?\n•Background incidence of SARS -CoV-2 infection was rapidly changing during bivalent booster uptake\n‒Analysis excluded cases with COVID -19 diagnosis or positive test in prior 30 days, although asymptomatic \ninfections and home antigen tests are not consistently documented in EHR; however, KPNC chart reviews did not \nfind recent SARS -CoV-2 infection or exposure24\nFurther evaluation and key next steps\nFurther evaluation\nContinue to monitor weekly and explore potential data- related explanations for the \nstatistical signal in VSD\nIn the process of chart reviewing a random sample of 100 cases across VSD sites\nConsult with other surveillance systems to better understand: \n•Possible role of simultaneous high- dose or adjuvanted flu vaccination with COVID -19 vaccination\n•Possible decreased rate of stroke in the 3– 6 weeks following vaccination\nKey next steps\nCDC continues to recommend that everyone eligible for a COVID -19 mRNA bivalent \nbooster or a flu vaccine get vaccinated\nCDC and FDA are engaged in epidemiologic analyses regarding simultaneous of \nCOVID -19 mRNA bivalent booster and flu vaccines\n25\nCOVID -19 mRNA bivalent booster vaccination safety –data \nfrom other monitoring systems and programs*\nNo unusual or unexpected reporting patterns observed, and no evidence of a safety \nconcern detected for ischemic stroke with either COVID -19 mRNA bivalent boosters in \nVaccine Adverse Event Reporting System (VAERS) monitoring (see supplemental slides)\nFDA monitoring in the CMS data and Department of Veterans Affairs monitoring in the VA system have not detected any safety signals for ischemic stroke following COVID -19 \nmRNA bivalent boosters using historical comparator designs \nSurveillance conducted by international regulatory and public health partners has not detected a safety concern for ischemic stroke following bivalent COVID -19 mRNA booster \nvaccination \nNo evidence of a safety signal for ischemic stroke in Pfizer’s global monitoring of bivalent COVID -19 mRNA booster vaccination\nNo safety signals were detected for ischemic stroke for primary series or monovalent \nboosters for Pfizer -BioNTech or Moderna COVID -19 vaccines in U.S. and global monitoring\n26*These surveillance activities did not include analyses to evaluate the effect of simultaneous flu vaccination; different \nformulations of COVID -19 mRNA bivalent booster vaccinations were used globally\nMyocarditis/pericarditis following \nCOVID- 19 mRNA vaccination in VSD\nNumber of COVID-19 bivalent booster doses administered over time among \npersons aged 12 -39 years, by vaccine type in VSD\n28\n* Bivalent booster data through January 29, 2023\n\nVSD incidence rates of verified myocarditis or pericarditis in the 0 –7 days \nafter Pfizer-BioNTech vaccination in people ages 12 –39 years*\n29Dose 2 primary series \nPfizer -BioNTech1stmonovalent booster dose \nPfizer -BioNTechBivalent booster dose\nPfizer -BioNTech\nAge/sex CasesDose 2\ntotalIncidence rate/\nmillion doses\n(95% CI)Cases1stbooster\ntotalIncidence rate/\nmillion doses\n(95% CI)CasesBivalent\nbooster\ntotalIncidence rate/\nmillion doses\n(95% CI)\n12–17 years\nMales\nFemales45\n6308,046\n311,247146.1 (106.6– 195.5)\n19.3 (7.1– 42.0)14\n2129,487139,118108.1 (59.1– 181.4)\n14.4 (1.7– 51.9)0048,066\n49,7250.0 (0.0– 62.3)\n0.0 (0.0– 60.2)\n18–29 years\nMales\nFemales27\n2331,889\n400,32181.4 (53.6– 118.4)\n5.0 (0.6– 18.0)71166,973240,22641.9 (16.9– 86.4)\n4.2 (0.1– 23.2)1\n050,687\n80,21119.7 (0.5– 53.1)\n0.0 (0.0– 37.3)\n30–39 years\nMales\nFemales5\n3341,527410,71314.6 (4.8– 34.2)\n7.3 (1.5– 21.3)31197,554268,41215.2 (3.1– 44.4)\n3.7 (0.1– 20.8)0\n082,191\n115,0140.0 (0.0– 36.4)\n0.0 (0.0– 26.0)\n* Primary series and 1stmonovalent booster data through August 20, 2022, bivalent booster data through January 29, 2023; Source: Goddard K, et \nal.Incidence of Myocarditis/Pericarditis Following mRNA COVID- 19 Vaccination Among Children and Younger Adults in the United States .Ann Intern Med. \n2022;175:1169- 1771.\nVSD incidence rates of verified myocarditis or pericarditis in the 0 –7 days \nafter Moderna vaccination in people ages 18 –39 years*\n30*P\nrimary series and 1st monovalent booster data through August 20, 2022, bivalent booster data through January 29, 2023; source: Goddard K, et al. Incidence of\nMyocarditis/Pericarditis Following mRNA COVID -19 Vaccination Among Children and Younger Adults in the United States .Ann Intern Med. 2022;175:1169- 1771.Dose 2 primary series \nModerna1stmonovalent booster dose \nModernaBivalent booster dose\nModerna\nAge/sex CasesDose 2\ntotalIncidence rate/\nmillion doses\n(95% CI)Cases1st\nbooster\ntotalIncidence rate/\nmillion doses\n(95% CI)CasesBivalent\nbooster\ntotalIncidence rate/\nmillion doses\n(95% CI)\n18–29 years\nMales\nFemales19\n0195,809\n243,56097.0 (58.4 – 151.5)\n0.0 (0.0 –12.3)71109,337156,70764.0 (25.7 – 131.9)\n6.4 (0.2 –35.6)0\n018,49929,5610.0 (0.0– 161.9)\n0.0 (0.0– 101.3)\n30–39 years\nMales\nFemales8\n1216,583259,78036.9 (15.9 – 72.8)\n3.9 (0.1 –21.4)12149,468191,7656.7 (0.2 –37.3)\n10.4 (1.3 –37.7)0\n035,31847,6200.0 (0.0– 84.8)\n0.0 (0.0– 62.9)\nAcknowledgements\n31CDC Immunization Safety Office\n•VAERS Team\n•V-safe Team\n•Clinical Immunization Safety Assessment \n(CISA) Project\n•Vaccine Safety Datalink (VSD) Team\nCOVID -19 Vaccine Task Force Data Monitoring \nand Reporting GroupKaiser Permanente Northern California (VSD)\nMarshfield Clinic Research Institute (VSD)\nVSD sites\n•HealthPartners Institute, Minneapolis, MN\n•Kaiser Permanente Colorado, Denver, CO\n•Kaiser Permanente Northwest, Portland, OR\n•Kaiser Permanente Southern California, Los Angeles, CA\n•Kaiser Permanente Washington, Seattle, WA\n•Denver Health, Denver, CO\nDisclaimer/disclosures\nThe findings and conclusions in this presentation are those of the presenters and \ndo not necessarily represent the official position of the CDC\nMention of a product or company name is for identification purposes only and does not constitute endorsement by CDC\nDr. Nicola Klein reports research support from Pfizer for COVID -19 vaccine clinical \ntrials and from Pfizer, GlaxoSmithKline, Merck and Sanofi Pasteur for unrelated studies\n32\nFor more information, contact CDC\n1-800-CDC- INFO (232- 4636)\nTTY:  1 -888- 232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.\nPhoto credit: James Gathany  \n(https://wwwn.cdc.gov/phil/\nDetails.aspx?pid=8876) \nVAERS and v- safe supplemental slides\nVAERS is the nation’s early warning system for vaccine safety\n+\nVaccine Adverse Event \nReporting System\nhttp://vaers.hhs.gov\n35\nU.S. reports to VAERS following bivalent booster COVID- 19 mRNA \nvaccination among ages ≥5 years* (as of February 6, 2023) (N=23,395)\nDistribution by age, sex, and serious status similar regardless of manufacturer\n•Most reports (94%) were non- serious\n•Race, ethnicity distribution comparable to monovalent COVID -19 mRNA vaccines \n(49% race and/or ethnicity unknown; 39% non- Hispanic white)ManufacturerMedian \nAge (IQR), \nyearsMale†\nN (%)Female†\nN (%)Non -serious\nN (%)Serious \nN (%)Doses\nadmin‡ \nPfizer- BioNTech 54 (33– 69) 5,450 (38) 8,750 (61) 13,496 (93) 944 (7) 33,676,379\nModerna 61 (44– 71) 3,378 (38) 5,457 (61) 8,460 (94) 495 (6) 19,076,635\nTotal 58 (37– 70) 8,828 (38) 14,207 (61) 21,956 (94) 1,439 (6) 52,753,014\n* Includes reports after Moderna bivalent booster among ages ≥6 years; † Excludes 360 (2%) reports where sex was not reported\n‡Doses administered among children ages 5– 11 years vaccinated during October 18, 2022– February 8, 2023 36\nMost frequent MedDRA Preferred Terms*to VAERS following Pfizer -BioNTech bivalent \nbooster vaccination among people ages ≥5 years (as of February 6, 2023)\nRank MedDRA PT (not mutually exclusive) n (%)\n1 COVID -19 1,785 (13)\n2 Fatigue 1,091 (8)\n3 Headache 1,067 (8)\n4 Pyrexia/fever 1,016 (8)\n5 SARS -CoV- 2 test positive 974 (7)\n6 Pain 969 (7)\n7 Cough 779 (6)\n8 Chills 677 (5)\n9 Dizziness 571 (4)\n10 Pain in extremity 554 (4)Non- serious reports (N=13,496)† Serious reports (N=944)\nRank MedDRA PT (not mutually exclusive) n (%)\n1 COVID -19 274 (29)\n2 SARS -CoV- 2 test positive 238 (25)\n3 Dyspoena 138 (15)\n4 Asthenia 109 (12)\n5 Condition aggravated 93 (10)\n6 Pyrexia/fever 87 (9)\n7 Death‡ 83 (9)\n8 Cerebrovascular accident 72 (8)\n9 Cough 71 (8)\n10 Fatigue 69 (7)\n* Medical Dictionary for Regulatory Activities Preferred Terms ( https://www.meddra.org/how -to-use/basics/hierarchy )\n†Clinical outcomes only, as determined by subject matter expert consensus\n‡Median age 80 years (IQR: 72– 88) 37\nMost frequent MedDRA Preferred Terms*to VAERS following Moderna bivalent booster \nvaccination among people ages ≥6 years (as of February 6, 2023)\nRank MedDRA PT (not mutually exclusive) n (%)\n1 COVID -19 877 (10)\n2 Headache 863 (10)\n3 Pyrexia/fever 858 (10)\n4 Fatigue 837 (10)\n5 SARS -CoV- 2 test positive 792 (9)\n6 Pain 751 (9)\n7 Cough 604 (7)\n8 Chills 536 (6)\n9 Pain in extremity 440 (5)\n10 Oropharyngeal pain 404 (5)Non- serious reports (N=8,460)†Serious reports (N=495)\nRank MedDRA PT (not mutually exclusive) n (%)\n1 COVID -19 146 (30)\n2 SARS -CoV- 2 test positive 134 (27)\n3 Dyspnoea 86 (17)\n4 Condition aggravated 50 (10)\n5 Death‡ 47 (9)\n6 Asthenia 46 (9)\n7 Pyrexia/fever 45 (9)\n8 Cough 44 (9)\n9 Anticoagulant therapy 42 (8)\n10 Dizziness 38 (8)\n38* Medical Dictionary for Regulatory Activities Preferred Terms ( https://www.meddra.org/how -to-use/basics/hierarchy )\n†Clinical outcomes only, as determined by subject matter expert consensus\n‡Median age 75 years (IQR: 66– 84)\nReports to VAERS of ischemic stroke/transient ischemic attack (TIA) after \nbivalent COVID -19 mRNA vaccination (as of February 6, 2023)\n67 verified reports of ischemic stroke/TIA\n•Median age: 73 years (IQR: 67 –79 years)\n•Median time to onset: 8 days (IQR: 3 –24 days)\n•28 males, 39 females\n•47 after Pfizer -BioNTech bivalent\n•20 after Moderna bivalentPreliminary reports of ischemic \nstroke/TIA (N=224)\nUnder review*\n(n=130)\nExcluded based \nupon chart \nreview (n=27)\nVerified by chart review (n=67)\n*Awaiting medical records and/or healthcare provider interview; some still processing \n39\nReporting rate to VAERS of ischemic stroke/transient ischemic attack \nafter bivalent COVID -19 mRNA vaccine in people ages ≥65 years  \n(as of February 6, 2023)\nIncidence of ischemic stroke among people ages ≥65 years = 670 –970 per \n100,000 person years†\n* Doses administered as of Feb 9, 2023; † Roger et al. Heart disease and stroke statistics— 2011 update: a report from the American Heart Association. Circulation 2011;123 :e18 –e20940Chart- verified reportsChart- verified reports \n+ reports under review\nManufacturer ReportsDoses \nadministered*Reporting rate \n(per million doses \nadministered)ReportsDoses \nadministered*Reporting rate \n(per million doses \nadministered)\nPfizer- BioNTech 47 13,217,119 2.9 139 13,217,119 8.4\nModerna 20 9,268,318 1.9 58 9,268,318 4.8\nV-safe: Smartphone-based active safety monitoring\nEnroll yourself or \nyour dependent \nafter any dose!\nhttps://vsafe.cdc.gov\n41\nReactions and health impacts reported by v-safe participants aged ≥5 years \nat least once 0 -7 days after first monovalent booster dose, by age group\n0102030405060708090100\nAny injection site reaction Any systemic reaction Any health impactPercentage5-11 y\n12-17\n≥18Age group ( yrs)\nData for participants aged ≥18 years as of October 23, 2022. Includes 677,009 participants who completed at least 1 survey in the first week after mRNA booster do se.\nData for participants aged 12 -17 years as of February 20, 2022. Includes 3,418 participants who completed at least 1 survey in t he first week after homologous booster dose. \nData for participants aged 5 -11 years as of July 31, 2022. Includes 3,249 participants who completed at least 1 survey in the fi rst week after homologous booster dose. 42\nReactions and health impacts reported by v-safe participants aged ≥5 years \nat least once 0 -7 days after bivalent booster dose, by age group\nData for participants aged ≥12 years as of October 23, 2022. Includes 311,205 participants who completed at least 1 survey in the first week after booster dose.\nData for participants aged 5 -11 years as of February 5, 2023. Includes 3,588 participants who completed at least 1 survey in the first week after booster dose. 0102030405060708090100\nAny injection site reaction Any systemic reaction Any health impactPercentage5-11 y\n12-17\n18-49\n50-64\n≥65Age group (yrs )\n43", "summary": "National Center for Emerging and Zoonotic Infectious Diseases COVID-19 mRNA bivalent booster vaccine safety Advisory Committee on Immunization Practices (ACIP) meeting February 24, 2023 Tom T. Shimabukuro, MD, MPH, MBA Director, Immunization Safety Office Division of Healthcare Quality Promotion Centers for Disease Control and Prevention (CDC)  Topics Describe CDC’s Vaccine  Safety Datalink (VSD) Rapid Cycle Analysis (RCA)  m onitoring methods and assessment processes for statistical signals…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/COVID-02-Shimabukuro-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 43}
{"title": "COVID 03 Forshee 508", "content": "Update on Original COVID -19 Vaccine and COVID -19 \nVaccine, Bivalent Safety\nRichard Forshee\nDeputy Director, FDA/CBER/OBPV\nAdvisory Committee on Immunization Practices\nFebruary 24, 2023 \n2\n•CBER Active Surveillance Program (BEST Initiative)\n•Bivalent COVID - 19 mRNA Vaccines Safety Surveillance\n•ConclusionOutline\n3\n*Data lag varies based on data source, ranges from a few days to a few months.\nBEST Initiative Data Sources\n4\nClaims Data Source Age (years)Population Enrolled \n(million)\nCMS Medicare 65+ 36\nDP 10-4\n5-17\n18-641.2\n3.1\n14.8\nDP 20-4\n5-17\n18-641.02.6 \n11.6 \nDP 30-4\n5-17\n18-641.43.7\n17.1Rapid Cycle Analysis (RCA) Data Sources\n5\n•Confidential, population- b ased, computerized \ndatabases that record immunization doses \nadministered by participating providers to persons in U.S. public health jurisdictions \n•Supplements claims- b\n ased COVID-19 vaccine \nadministration data\n•Undercapture o f COVID-19 vaccines in claims \ndatabases due to vaccines administered without insurance reimbursementImmunization Information Systems (IIS)\n6\nDescriptive Monitoring provides descriptive statistics of \nvaccine doses and selected adverse events.\nSignal Detection performs sequential testing, while \nvaccine doses accumulate, to identify potential safety \nrisks early; does not prove causal relationship.\nSignal Evaluation uses more robust study designs to \nevaluate potential safety signals.Phases of Vaccine Active Surveillance\n7\n•CBER Active Surveillance Program (BEST Initiative)\n•Bivalent COVID-19 mRNA Vaccines Safety Surveillance\n•ConclusionOutline\n8\nCOVID-19 Bivalent mRNA Vaccines Rapid Cycle Analyses \nAdministered Doses By Age Group\n1. Data cuts: CVS data through 10/2022, HealthCore data through 11/2022, Optum data through 12/2022 \n2. Data cuts: CMS data through 12/2022Age Groups \n(years)BNT162b2 \n(# vaccinations)mRNA-1273 \n(# vaccinations)Total \n(# vaccinations)\n5/6-171196,992 13,016 210,008\n18-351442,870 211,694 654,564\n36-641 1,248,430 654,220 1,902,650\n65+2 4,265,244 3,042,074 7,307,318\n\n9\n•FDA Study Design: Rapid Cycle Analysis (RCA) near real-time \nsurveillance \n•No causal association established\n•Population: 6 month-4/5 years, 5/6-17 years, 18-64 years*, ≥65 \nyears\n•Exposure: mRNA -1273.222 and BNT162b2 COVID -19 vaccines\n•Bivalent booster: original SARS-CoV -2 virus and Omicron \nvariants BA.4 and BA.5.\n•Statistical Method : MaxSPRT\n•Comparator: Historical rates \n*For the myocarditis/pericarditis outcome, the study population was additionally split into 18- 35 and 36 -64year age groups.COVID- 19 Bivalent mRNA Vaccines Safety Monitoring\n10\nAdverse Events Monitored in Adult and Pediatric Populations\nAcute Myocardial Infarction Hemorrhagic Stroke \nAnaphylaxis Immune Thrombocytopenia  \nAppendicitis Multisystem Inflammatory Syndrome \nBell’s Palsy Myocarditis/Pericarditis (Myo- /Pericarditis)*\nCommon Site Thrombosis with \nThrombocytopeniaNarcolepsy \nDisseminated Intravascular Coagulation Non- hemorrhagic Stroke \nDeep Vein Thrombosis  Pulmonary Embolism  \nEncephalitis/Encephalomyelitis Transverse Myelitis \nGuillain -Barre Syndrome Unusual Site Thrombosis (Broad) with \nThrombocytopenia\n*This includes 4 myo -/pericarditis outcome definitions varying care settings (all settings vs. IP/OP -ED) and risk windows (1 -7 vs. 1-21 days)\nThese AEs have not been associated with COVID- 19 vaccines based on available pre- licensure evidence.Adverse Events Monitored in\nPediatric Populations Only\nSeizure/Febrile Seizure\nKawasaki Disease\nMultisystem Inflammatory Syndrome in children \n(MIS -C) FDA Adverse Events Monitored \n\n11\nAdverse Event (AE)Medicare Population1\n(Ages 65+)Adult Population2\n(Ages 18-64)Pediatric Population2\n(Ages 5-17/6-17)\nAcute Myocardial Infarction No No Descriptive Only\nAnaphylaxis No No No\nAppendicitis No No No\nDisseminated Intravascular Coagulation No No No\nDeep Vein Thrombosis No No No\nBell’s Palsy No No No\nEncephalomyelitis/Encephalitis No No No\nGuillain -Barré Syndrome No No Descriptive Only\nHemorrhagic Stroke No No Descriptive Only\nMyocarditis/Pericarditis NoBNT162b2 Bivalent \n(18-35)No\nCommon Site Thrombosis with \nThrombocytopeniaNo No No\nUncommon Site Thrombosis with Thrombocytopenia SyndromeNo No Descriptive Only\nNarcolepsy No No No\nNon-Hemorrhagic Stroke No No No\nPulmonary Embolism No No No\nTransverse Myelitis No No Descriptive Only\nImmune Thrombocytopenia No No No\nFebrile Seizures N/A N/A Descriptive Only\nSeizures/Convulsions N/A N/A No\nKawasaki disease N/A N/A Descriptive Only\nMultisystem Inflammatory Syndrome Descriptive Only Descriptive Only Descriptive Only\n1. Data cuts: CMS 12/2022\n2. Data cuts: CVS Health data through 10/2022; HealthCore data through 11/2022, Optum data through 12/2022\nA\nEs and the associated vaccine brand with a safety signal are noted. \nN/A indicates neither descriptive monitoring nor sequential testing is being conducted in the indicated age group for a given AE . NOindicates that a safety signal has \nnot been detected. Descriptive Only indicates sequential testing is not being conducted in the indicated age group for a given AE.Signals Detected\n\n12\nAdverse Event (AE) Ages 65+ years\nAcute Myocardial Infarction BNT162b2, mRNA- 1273\nDeep Vein Thrombosis BNT162b2, mRNA- 1273\nBell’s Palsy BNT162b2\nCommon Site Thrombosis with \nThrombocytopeniaBNT162b2\nNon-Hemorrhagic Stroke BNT162b2, mRNA- 1273\nPulmonary Embolism BNT162b2Adverse Events that Completed Surveillance Period\n13\nRisk Ratio Non -hemorrhagic Stroke for Pfizer\nBivalent Compared to Historical Rates (2019)\nWe reached the maximum length of surveillance without a signal\n14\n•Approximately  4. 25 million doses of the Pfizer -BioNTech bivalent vaccine have \nbeen administered in the CMS database in individuals 65 years and older\n•38% of the Medicare recipients who received a Pfizer bivalent COVID-19 \nb\nooster received a seasonal influenza vaccination on the same day\n•78% received a seasonal influenza vaccination within +/- 4 2 days \n•Further work to be done to segment out the different influenza vaccine types \nadm\ninistered with the COVID-19 vaccines\n•No signal seen at this time for non-hemorrhagic strokeConcomitant Influenza Vaccination\n15\n•This is a large-scale signal detection study of two COVID-19 mRNA bivalent \nvaccines conducted in multiple claims databases. \n•RCA surveillance detected a signal for myocarditis/pericarditis following BNT162b2 bivalent vaccine doses among 18-35 year olds.\n•Among adults 65 years and older, several AEs have completed the surveillance period. \n•Signal detection studies do not establish a causal relationship and further evaluation of signals is required in more robust studies.\n•Surveillance is ongoing and expanded to < 5 year olds. COVID- 19 Bivalent mRNA Vaccines RCA\nSummary\n16\n1)No excess reports of stroke from VAERS\n2)CMS database with about 4.25 million doses shows no increase in stroke\n3)VA database run shows no increase in stroke on preliminary query\n4)Various countries in Europe as well as Israel indicate no increased risk of stroke in \ntheir surveillance systems\n5)Pfizer notes no increase in signal in their global safety database or when comparing the monovalent to bivalent vaccines\nIn any case, a formal epidemiologic study is being initiated by FDA to \nprepare for potential vaccine coadministration in 2023-2024Data Suggesting Absence of Safety Risk for the \nBivalent Boosters in Age 65y+\n17\nAcknowledgements\n•Steven A. Anderson\n•CBER Surveillance T eam: Azadeh Shoaibi, Hui-Lee Wong, Tainya C. Clarke, \nJoyce Obidi, Joann F. Gruber, Patricia C. Lloyd, Sylvia Cho\n•CBER OBPV\n•Federal Partners: CMS, VA, CDC\n•FDA Partners: Acumen, Blue Health Intelligence, CVS Health, Healt hCore, \nIBM, IQVIA, OHDSI, Optum, RTI Health Solutions\nwww.bestinitiative.org", "summary": "Update on Original COVID -19 Vaccine and COVID -19  Vaccine, Bivalent Safety Richard Forshee Deputy Director, FDA/CBER/OBPV Advisory Committee on Immunization Practices February 24, 2023  2 •CBER Active Surveillance Program (BEST Initiative) •Bivalent COVID - 19 mRNA Vaccines Safety Surveillance •ConclusionOutline 3 *Data lag varies based on data source, ranges from a few days to a few months. BEST Initiative Data Sources 4 Claims Data Source Age (years)Population Enrolled  (million) CMS…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/COVID-03-Forshee-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 17}
{"title": "COVID 04 Talbot 508", "content": "COVID-19 Vaccine Safety Technical (VaST) \nWork Group \nVaST assessment\nH. Keipp Talbot, MD MPH (VaST Chair)\nRobert H. Hopkins, Jr., MD (NVAC Chair )\nAdvisory Committee on Immunization Practices\nFebruary 24, 2023\nCOVID -19 Vaccine Safety Technical (VaST) Work Group\nObjectives\nReview, evaluate, and interpret post -a uthorization/approval COVID -19 \nvaccination safety data\nServe as the central hub for technical subject matter expertise from \nfe\nderal agencies conducting post-authorization/approval safety \nmonitoring\nAdvise on analyses, interpretation, and presentation of vaccine safety data\nProvide updates to the ACIP COVID -19 Vaccines Work Group and the \nentire ACIP on COVID -19 vaccine safety\n2\nActivities\nFrom December 21, 2020 through February 24, 2023\n–\n––71 independent meetings to review vaccine safety data17 joint meetings with ACIP COVID-19 Vaccines Work Group22 ACIP meeting presentations or reports with VaST assessments\n3COVID -19 Vaccine Safety Technical (VaST) Work Group\nVaST assessment\nStatistical signal for ischemic stroke in the Vaccine Safety Datalink \nfo\nllowing bivalent COVID -19 booster vaccination \nMyocarditis/pericarditis following mRNA COVID-19 vaccination \n4\nThe statistical signal among persons aged ≥ 65 years for ischemic stroke/transient \nis\nchemic attack (TIA) following bivalent Pfizer-BioNTech COVID -19 booster vaccination \nin VSD is based on limited data and has been attenuating over time.   \nA signal has not been observed in two other U.S. active vaccine safety monitoring sy\nstems1, nor in data from other countries2. \n–The U.S. systems differ from each other; the VSD and VA analyses included TIA w\nith ischemic stroke, while FDA CMS analysis did not.\n–VSD is the only U.S. system that uses concurrent comparator groups .\n–The VA and FDA CMS analyses have not evaluated simultaneous administration w\nith influenza vaccination.\n5VaST assessment –statistical signal for ischemic \nstroke/TIA in the Vaccine Safety Datalink (VSD)\n1FDA analysis of Centers for Medicare and Medicaid Services (CMS) data, and Department of Veterans Affairs (VA) rapid cycle an alyses\n2Israel and European countries\nNo increased rate ratio for ischemic stroke/TIA following bivalent Moderna COVID -19 \nbooster vaccination . \nPrevious surveillance in VSD and other U.S. systems found no evidence of increased \nrisk of ischemic stroke/TIA after the primary series or monovalent COVID -19 booster \nvaccination for either Pfizer- BioNTech or Moderna products. \n6VaST assessment –statistical signal for ischemic \nstroke/TIA in the Vaccine Safety Datalink (VSD)\nThe cause of the increased rate ratio is unclear; potential contributing factors include \ns\nimultaneous administration of bivalent COVID -19 booster and influenza vaccines* or \nunmeasured confounding or bias.\nVaST would like to review additional data on simultaneous administration of bivalent C\nOVID -19 booster and influenza vaccination. \nVaST highlighted several areas for further exploration:\n–\n–Assess the impact of recent respiratory viral illness (e.g., COVID -1 9, influenza) on \nrisk of ischemic stroke/TIA.\nAnalyses in VSD h ighlighted potential reasons for the lower rate of ischemic \nstroke/TIA in the vaccinated comparator group, which could be contributing to the \nincreased rate ratio. These should be explored further. \n7VaST assessment –statistical signal for ischemic \nstroke/TIA in the Vaccine Safety Datalink (VSD)\n*Most VSD participants aged≥ 65 years received high- dose influenza vaccine in 2022 -23 season\nVaST has reviewed data on myocarditis/pericarditis following COVID -1 9 vaccination  \nsince April 2021 and provided several assessments at ACIP meetings.\n–\n–\n–\n–Rates a fter the monovalent primary series, monovalent booster doses and \nbivalent booster doses have been assessed. \nRates h ighest in adolescent and young adult males following primary series \ndose 2 and first monovalent booster dose.\nOutcomes after the monovalent primary series and monovalent booster doses \nh\nave also been assessed.\nData on rates after bivalent COVID- 1 9 booster vaccination are limited. \nCurrent data in VSD do not raise additional concerns about myocarditis f\nollowing bivalent COVID -19 booster vaccination. \n8VaST assessment –myocarditis/pericarditis following \nmRNA COVID-19 vaccination \nThe ACIP COVID -19 Vaccines Work Group will continue to review safety data\nVaST is preparing to transition review of vaccine safety data to the ACIP COVID -19 \nVaccines Work Group\n9VaST –future plans\nVaST Members\nVaST Members\nKeipp Talbot (ACIP)\nRobert Hopkins (NVAC)\nMatt Daley\nGrace Lee\nVeronica McNallyKathy EdwardsLisa JacksonJennifer NelsonLaura Riley\nRobert Schechte r\nPatricia Whitley -Williams\nCDC Co -Leads\nLauri Markowitz\nMelinda WhartonEx Officio and Liaison Representatives \nTatiana Beresnev (NIH)Karen Farizo; Hui Lee Wong (FDA)\nValerie Marshall (OIDP)\nJeffrey Kelman (CMS)Matthew Clark (IHS)Timothy Styles (HRSA)Fran Cunningham (VA)\nMargaret Ryan (DoD)\nAdministrative Support\nJared Woo\n1010", "summary": "COVID-19 Vaccine Safety Technical (VaST)  Work Group  VaST assessment H. Keipp Talbot, MD MPH (VaST Chair) Robert H. Hopkins, Jr., MD (NVAC Chair ) Advisory Committee on Immunization Practices February 24, 2023 COVID -19 Vaccine Safety Technical (VaST) Work Group Objectives Review, evaluate, and interpret post -a uthorization/approval COVID -19  vaccination safety data Serve as the central hub for technical subject matter expertise from  fe deral agencies conducting…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/COVID-04-Talbot-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 10}
{"title": "COVID 05 Twentyman 508", "content": "cdc.gov/coronavirus\nIschemic Stroke, COVID -19 and Influenza in \nAdults Ages ≥65 Years:\nInterpretation & Next Steps\nEvelyn Twentyman, MD, MPH\nACIP MeetingFebruary 24, 2023\nStatistical signal for \nischemic stroke identified in Vaccine Safety Datalink (VSD) Rapid Cycle Analysis (RCA) monitoringIschemic stroke, COVID -19, and influenza in review\nNew and published data regarding relationships of ischemic stroke, COVID -19, and influenza Work group interpretation and next steps\nStatistical signal for \nischemic stroke identified in VSD RCA monitoringIschemic stroke, COVID -19, and influenza in review\nNew and published data regarding relationships of ischemic stroke, COVID -19, and influenza Work group interpretation and next steps\nStatistical signal identified for ischemic \ns\ntroke after Pfizer -BioNTech COVID -19 \nmRNA bivalent booster dose vaccination in age group 65+ years in VSD RCA \n–Rate ratio has attenuated over timeReview of statistical signal\n:\nSupplemental analysis comparing b\noosted to un -boosted concurrent \ncomparators did not show an elevated rate ratio:\nComparing rates in an early (“risk”) interval with rates in a later (“comparison”) intervalComparing rates in the early (“risk”) interval among boosted people vs booster eligible un-boosted people\nStratified analysis evaluating people \nw\nith coadministration of high -dose or \nadjuvanted flu vaccination show a rate ratio of 1.65 (1.02—2.72; p=0.04)In the stratified analysis, rate ratio w\nas not elevated in people who \nreceived Pfizer- BioNTech bivalent \nmRNA booster without simultaneous \nflu vaccine\nSeparate analysis did no t detect an \nelevated rate ratio for ischemic stroke after flu vaccine aloneReview of statistical signal: coadministration\n*Coadministration refers to administration of >1 vaccine in the same day.Pfizer bivalent mRNA Coadministration*High -do se/ adjuvanted flu vaccine\nNo other VSD RCA pre -s pecified surveillance outcomes have signaled:\n–\n––\n–\n–––\n–in any age groups,\nfore ither of the mRNA COVID -19 bivalent booster vaccines, or\nwhen data for the two mRNA vaccine types are combined.\nNo evidence of a safety signal for ischemic stroke in other safety monitoring \ns\nystems, though analyses in these systems generally did not have the ability to \ninvestigate coadministration with flu vaccine\nVaccine Adverse Events Reporting System (VAERS)\nFDA Rapid Cycle Analysis (RCA) data in Centers for Medicare & Medicaid Services (CMS)Veterans Administration (VA) RCA in the VA Electronic Health Record (VA EHR)\nPfizer global monitoring\nOther global public health and regulatory systems\n•Canada\n•European Union\n•IsraelReview of statistical signal: not identified in any other \nvaccine safety monitoring system\nStatistical signal for \nischemic stroke identified in VSD RCAIschemic stroke, COVID -19, and influenza in review\nNew and published data regarding relationships of ischemic stroke, COVID -19, and influenza Work group interpretation and next steps\nIncidence of AIS hospitalizations was 10 times higher during \nthe 3 days post COVID diagnosis (IRR 10.3, [9.9 –10.8]) \ncompared with control periods, among Medicare beneficiaries \nages ≥65 years1\nCOVID cohort estimated incidence of AIS is 2.10% (1. 97—2.23) \nwithin 6 months after COVID diagnosis2, though stroke and \nCOVID symptoms present concomitantly in >80% of cases3\nCOVID -1 9 patients who develop stroke are more likely to be of older age, have more severe COVID- 19 disease , and more \nlikely to have hypertension, diabetes, and coronary artery disease than those who do not\n3\nCOVID -19v accination is associated with reduced risk of AIS \nafter COVID -19 (aHR 0.40 [0.26-0.63]; aHR 0.41 [0.26- 0.66] for \nages ≥65)4Percentage Hospitalized \nCOVID Patients Aged 65+ \nwith Stroke: \nCOVID -NET, March \n2020—October 2022COVID -19 disease and acute ischemic stroke (AIS)\n1) Yang Q et al. Neurology 2022; 98(8): e778- 789. 2) Taquet M et al. Lancet Psychiatry 2021; 8(5): 416- 427. 3) Nannoni S et al.  International Journal of Stroke 2021; 16(2): \n137-149. 4) Kim Y et al. JAMA 2022; 328(9): 887- 889.1%2%3%\nAlpha Delta Omicron \n(early)Omicron \n(late)2.2%\noverall\nAssociation between recent respiratory infection and increased stroke risk noted in \nso\nme observational studies 1,2\nTwo randomized studies assessing stroke as a specific outcome did not note a s\nignificant effect of influenza vaccination on stroke risk 3, 4\nStroke has been evaluated as an outcome in several observational studies, some of w\nhich have reported decreased risk with vaccination 5-8\nBenefit of influenza vaccination has been noted in some studies examining major c\nardiovascular outcomes (some including stroke within a composite outcome) 4,8\nLimitations:\n––––Potential reduction in stroke risk varies and is not seen in all studiesPopulations, study designs, outcome definitions, and analytic methods vary across studiesObservational data are more subject to biasOverall limited data concerning specific influenza vaccines and stroke -s\n pecific riskInfluenza, Influenza Vaccination, and Stroke\n1. Smeeth L et al, N Engl J  Med 2004; 351: 2611 -8\n2. Zurrú M C et al, Stroke 2009; 40: 1986 -90\n3. Loeb M et al, Lancet Global Health 12 2022; 10: e1835 -e 1844 \n4. Phrommintikul A et al, Eur Heart J 2011; 32: 1730 –17355. Holodinsky JK  et al, Lancet Resp Health 2022; 7:  e914 -e922 \n6. Rodriguez -M artin S et al, Neurology 2022; 00: e2199 -e2160\n7. Asghar Z et al, Vaccine 2015; 33: 5458 -5463\n8. Chiang MH et al, Am Heart J 2017; 193: 1 -7\nPCORnet©The National Patient -\nCentered Clinical Research Network\nData includes el ectronic health records \nassociated with ambulatory, ED, and \ninpatient settings\nCovers a ll patients in participating \nhealth systems, or ~ 10% of the US \npopulation ages ≥65 years\nUsed to rapidly assess incidence of s\ntroke across diverse US population over \nthe late Omicron period within 2022, with recent COVID-19 or influenza and incidence overallHealthVerity\nData includes m edical claims from closed \npayor systems related to ambulatory, ED, and inpatient settings\nData is l\ninked to vaccination data from \nthe Federal Retail Pharmacy Program\nCovers patients i nsured through \nMedicare Advantage, or ~25% of the US population ages ≥65 years\nUsed to rapidly assess incidence of stroke a\ncross insured US population, with \nrecent COVID-19 or influenza vaccination and incidence overallHealthcare data sources used to describe current \nincidence of stroke\nPCORnet©The National Patient -Centered \nClinical Research Network\nCohort definitions designed to capture \ni\nncident stroke\n––\n–\n–\n–\n–\n–\n––––\n–\n–\n–\n–ICD10 diagnosis (I63.X)Exclusion of \n patients with history of stroke\nCohort definitions designed to capture p\natients with recent COVID -19 and influenza\nPositive laboratory tests (COVID -19 and influenza)\nICD10 diagnoses (B97.29, U07.1, J10.1, J10.2, J11.1, J 11.2, \nJ09.X, J10.8X, J11.8X)COVID -19 m\nedicationsNo COVID -19 i\n n the 30 days prior\nDescription of incidence of stroke across:\nEntire cohort, using average incidence over 32 days\nRecent COVID or flu diagnosis: 3 days prior to 28 days p ostHealthVerity\nCohort definitions designed to capture i\nncident stroke\nICD10 diagnosis (I63.X)Inpatient place of serviceExclusion of \n patients with history of stroke\nCohort definitions designed to capture r\necent bivalent mRNA and influenza \nvaccination\nAll applicable CVX, CPT/HCPCS, and NDC codesNo evidence of prior s\n troke/TIA during observation \nperiod or COVID -19 in the 30 days prior\nDescription of incidence of stroke across:\nEntire cohort, using average incidence over 29 daysRecent vaccination: within 28 days following bivalent m\nRNA vaccination, flu vaccination, or \ncoadministration of both vaccinesMethods used to describe current incidence of stroke\n010002000300040005000600070008000900010000\n*Average stroke incidence among adults aged 65+ in Sep -Dec 2022 in the full PCORnet cohort per million over 32 days.Stroke incidence among all adults ages ≥65 years, with COVID -19, and with \ninfluenza during late Omicron: PCORnet , Sep- Dec 2022Stroke incidence per million \nAll adults ≥65 ,\nover 32 days*All adults ages ≥65 \n(N=1,953,391)\nAdults ages ≥65 with COVID-19 (N=77,981)\nAdults ages ≥65 with influenza (N=11,396)\nAdults ≥65 with \ninfluenza , \n-3 to 28 daysAdults ≥65 with \nCOVID -19, \n-3 to 28 daysGroups presented are of the \nsame agecategory and \nadjusted time at risk. Crude \nincidence within groups is not \notherwise adjusted. \n010002000300040005000600070008000900010000\n*Average stroke incidence among adults aged 65+ in Sep -Dec 2022 in the full PCORnet cohort per million over 32 days.Early stroke incidence among adults ages 65+ years with COVID -19, and with \ninfluenza during late Omicron: PCORnet , Sep- Dec 2022Stroke incidence per million\nAll adults ≥ 65,\nover 32 days*All adults ages ≥65\n(N=1,953,391)\nAdults ages ≥65 with COVID-19 (N=77,981)\nAdults ages ≥65 with influenza (N=11,396)\nAdults ≥65 with \ninfluenza , \n-3 to 28 daysAdults ≥65 with \nCOVID -19, \n-3 to 28 daysIncidence within -3\nto 7 days of \nCOVID-19 disease \n(93.5%)Incidence within -3\nto 7 days of \ninfluenza infection \n(90.9%)\nGroups presented are of the \nsame agecategory and \nadjusted time at risk. Crude \nincidence within groups is not \notherwise adjusted. \n02004006008001000120014001600Stroke incidence among all adults ages ≥65 years and recently vaccinated \nadults ages 65+ years during late Omicron: HealthVerity, Sep -Oct 2022\n*Average stroke incidence among adults aged 65+ in Sep -Oct 2022 in the full HealthVerity cohort per million over 29 days.Stroke incidence per millionAll adults ages ≥65\n(N=3,651,579)\nAdults ages ≥65 with \nrecent bivalent mRNA \nvaccination(N=593,766)\nAdults ages ≥65 with \nrecent influenza \nvaccination(N=875,170)\nAdults ages ≥65 with \nrecent coadministration\nof bivalent mRNA + influenza vaccines (N=164,836)\nAdults ≥65 with \nflu vaccine , \n0 to 28 daysAdults ≥ 65 with \nbivalent mRNA , \n0 to 28 daysAdults ≥65 with \ncoadministration, \n0 to 28 daysAll adults ≥65 ,\nover 29 days*Groups presented are of the same \nagecategory and adjusted time at \nrisk. Crude incidence within groups \nis not otherwise adjusted. \nStatistical signal for \nischemic stroke identified in VSD RCA monitoringIschemic stroke, COVID -19, and influenza in review\nNew and published data regarding relationships of ischemic stroke, COVID -19 disease, and \ninfluenza Work group interpretation and next steps\nReview of safety data is reassuring, and must continue. Priorities include:\n–\n–\n–\n–Continuing to closely follow the intermittently statistically significant signal in VSD, \nw\nith continued review by VaST and colleagues\nContinuing supplementary analyses to clarify the relationship between this signal an\nd:\n•any specific vaccine\n•coadministration of vaccines\n•confounding\nContinuing the most intensive vaccine safety surveillance in US history\nReview of healthcare data demonstrates high incidence of stroke at time of diagnosis w\nith COVID -19 or influenza. Priorities include:\nIncreasing awareness of the risk of stroke with COVID -1 9 disease and influenza\n–Continuing to encourage uptake of the bivalent COVID -1 9 boostersWork group interpretation and next steps\nThe COVID -1 9 ACIP Work Group remains confident in current COVID -\n19 vaccine recommendations.\n–No changes to current recommendations regarding \ncoadministration of vaccines\nCDC and partners anticipate the opportunity to review and consider \nupc\noming analyses prior to the 2023 -2024 flu season.Work group interpretation and next steps\nTegan Boehmer\nMatt Ritchey\nJulia Raykin\nSharon Saydah\nStacey Adjei\nJennifer Wiltz\nJason Block\nPCORnet Sites\nSara Baca\nLisa Groskopf\nJill Ferdinands\nJanet Wright\nFátima Coronado\nSandra JacksonAcknowledgements\nVaST Working Group\nLauri Markowitz\nRobert Merritt\nXin (Cindy) Tong\nHilda Razzaghi\nCatherin Bozio\nMorgan Najdowski\nShikha Garg\nCarrie Reed\nAaron Kite -Powell\nKathleen Hartnett\nFiona Havers\nChris Taylor\nCOVIDNetAdi Gundlappali\nAaron Harris\nEmily Koumans\nPragna Patel\nJennifer Giovanni\nMark Swancutt\nKarl Soetebier\nTom Shimabukuro\nEric Weintraub\nKaren Broder\nImmunization Safety \nOffice\nErika Edding\nAron HallSara Oliver\nKatherine Fleming -\nDutra\nRuth Link -Gelles\nDanielle Moulia\nMegan Wallace\nMonica Godfrey\nJulianne Gee\nKelcie Landon\nBen Silk\nSarah Meyer\nElisha Hall\nMelinda Wharton\nBarbara Mahon\nFor more information, contact CDC\n1-800-CDC- INFO (232- 4636)\nTTY:  1 -888- 232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position o f the Centers for Disease Control and Prevention.\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation use. No rights are implied or extended for use in printing or \nany use by other CDC CIOs or any external audiences.", "summary": "cdc.gov/coronavirus Ischemic Stroke, COVID -19 and Influenza in  Adults Ages ≥65 Years: Interpretation & Next Steps Evelyn Twentyman, MD, MPH ACIP MeetingFebruary 24, 2023 Statistical signal for  ischemic stroke identified in Vaccine Safety Datalink (VSD) Rapid Cycle Analysis (RCA) monitoringIschemic stroke, COVID -19, and influenza in review New and published data regarding relationships of ischemic stroke, COVID -19, and influenza Work group interpretation and next steps Statistical signal…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/COVID-05-Twentyman-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 19}
{"title": "COVID 06 Taylor 508", "content": "National Center for Immunization & Respiratory Diseases\nTrends in COVID -19-Associated Hospitalizations —COVID -19-Associated \nHospitalization Surveillance Network (COVID -NET), March 2020–February 2023\nChristopher A. Taylor, PhD\nEpidemiologist, COVID -NET\nCoronaviruses and Other Respiratory Viruses Division\nNational Center for Immunizations and Respiratory DiseasesCenters for Disease Control and Prevention\nAdvisory Committee on Immunization Practices\nFebruary 24, 2023\n\nWeekly Population-Based Rates of COVID -19-Associated Hospitalizations \namong All Ages —COVID -NET, March 2020 –February 2023\n020406080100120140\n3/7/2020\n4/7/2020\n5/7/2020\n6/7/2020\n7/7/2020\n8/7/20209/7/2020\n10/7/202011/7/2020\n12/7/2020\n1/7/2021\n2/7/2021\n3/7/2021\n4/7/2021\n5/7/2021\n6/7/2021\n7/7/2021\n8/7/20219/7/2021\n10/7/202111/7/2021\n12/7/2021\n1/7/2022\n2/7/2022\n3/7/2022\n4/7/2022\n5/7/2022\n6/7/2022\n7/7/2022\n8/7/20229/7/2022\n10/7/202211/7/2022\n12/7/2022\n1/7/2023Rate per 100,000 population\nWeek Ending Date\n≤17 years 18–49 years 50–64 years 65–74 years ≥75 years\nGray boxes indicate potential reporting delays. Interpretation of trends should be excluded from these weeks. 2\nWeekly Population-Based Rates of COVID -19-Associated Hospitalizations \namong Adults Ages ≥18 Years — COVID -NET, March 2020 –February 2023\n020406080100120140Rate per 100,000 population\nWeek Ending DateMarch 2020 –February 2023 (entire pandemic period)\n18–49 years 50–64 years 65–74 years ≥75 years020406080100120140Rate per 100,000 population\nWeek Ending DateAugust 2022– February 2023\nGray boxes indicate potential reporting delays. Interpretation of trends should be excluded from these weeks. 3\nWeekly Population -Based Rates of COVID -19-Associated Hospitalizations among \nChildren and Adolescents Ages ≤17 Years —COVID- NET, March 2020 –February 2023\n0102030405060708090Rate per 100,000 population\nWeek Ending DateAugust 2022– February 2023\n0102030405060708090Rate per 100,000 population\nWeek Ending DateMarch 2020 –February 2023 (entire pandemic period)\n<6 months 6 months–<2 years 2–4 years 5–11 years 12–17 years\nGray boxes indicate potential reporting delays. Interpretation of trends should be excluded from these weeks. 4\nWeekly Proportions of COVID-19-Associated Hospitalizations by \nAdult Age Group — COVID-NET, March 2020 –February 2023\n0%10%20%30%40%50%60%70%80%90%100%\n3/7/2020\n4/11/2020\n5/16/2020\n6/20/2020\n7/25/2020\n8/29/202010/3/202011/7/2020\n12/12/2020\n1/16/20212/20/20213/27/2021\n5/1/20216/5/2021\n7/10/20218/14/20219/18/2021\n10/23/2021\n11/27/2021\n1/1/20222/5/2022\n3/12/20224/16/20225/21/20226/25/20227/30/2022\n9/3/2022\n10/8/2022\n11/12/2022\n12/17/2022\n1/21/2023March 2020 –February 2023 (entire pandemic period)\n18–49 years 50–64 years 65–74 years ≥75 years0%10%20%30%40%50%60%70%80%90%100%\n8/6/2022\n8/20/2022\n9/3/2022\n9/17/2022\n10/1/2022\n10/15/2022\n10/29/2022\n11/12/2022\n11/26/2022\n12/10/2022\n12/24/2022\n1/7/2023\n1/21/2023\n2/4/2023August 2022– February 2023\n40% of hospitalizations are\nin adults ages ≥75 years .\n5\nWeekly Proportions of COVID-19-Associated Hospitalizations by \nPediatric Age Group — COVID-NET, March 2020 –February 2023\n0%10%20%30%40%50%60%70%80%90%100%\n3/7/2020\n4/11/2020\n5/16/2020\n6/20/2020\n7/25/2020\n8/29/2020\n10/3/2020\n11/7/2020\n12/12/2020\n1/16/2021\n2/20/2021\n3/27/2021\n5/1/2021\n6/5/2021\n7/10/2021\n8/14/2021\n9/18/2021\n10/23/2021\n11/27/2021\n1/1/20222/5/2022\n3/12/2022\n4/16/2022\n5/21/2022\n6/25/2022\n7/30/2022\n9/3/2022\n10/8/2022\n11/12/2022\n12/17/2022\n1/21/2023March 2020 –February 2023 (entire pandemic period)\n<6 months 6 months –<2 years 2–4 years 5–11 years 12–17 years0%10%20%30%40%50%60%70%80%90%100%\n8/6/2022\n8/20/2022\n9/3/2022\n9/17/2022\n10/1/2022\n10/15/2022\n10/29/2022\n11/12/2022\n11/26/2022\n12/10/2022\n12/24/2022\n1/7/2023\n1/21/2023\n2/4/2023August 2022– February 2023\n6\nProportions of COVID- 19-Associated Hospitalizations with COVID -19 as a Likely Reason for \nAdmission by Age and Variant Predominance Period —COVID -NET, June 2020– November 2022\n0102030405060708090100\nTotal 0–4 years 5–11 years 12–17 years 18–49 years 50–64 years ≥65 yearsWeight % of hospitalizations\nPeriod of variant predominance\nPre-Delta (6/1/20–6/19/21)\nDelta (6/20–12/18/21)\nOmicron BA.1 (12/19/21–3/19/22)\nOmicron BA.2 (3/20–6/18/22)\nOmicron BA.5 and later (6/19 –11/30/2022)•Many children ages \n≤4 years and adults \nages ≥50 years are \nstill admitted for \nCOVID.\n•Adolescents and younger adults ( ages \n12–49 years ) are \nless likely to be \nadmitted for COVID .\n7\nUnderlying Medical Conditions among Non -Pregnant Adults \nAges ≥18 Years — COVID-NET, June–November 2022\n68.6\n54.6\n35.032.5 30.7\n24.6\n17.514.9\n9.75.3\n01020304050607080Weighted % of hospitalizations\nData are limited to hospitalizations where COVID -19 is a likely primary reason for admission.96% of hospitalized adults have\n≥1 underlying medical condition .\n8\nUnderlying Medical Conditions among Children and Adolescents \nAges ≤17 Years — COVID-NET, June– November 2022\n13.1\n11.2\n8.8 8.8\n7.9\n6.7 6.6 6.4\n5.3\n3.5 3.4\n2.62.2\n02468101214Weighted % of hospitalizations\nData are limited to hospitalizations where COVID -19 is a likely primary reason for admission.49% of hospitalized children and \nadolescents have no underlying \nmedical conditions .\n9\nUnderlying Medical Conditions among Children and \nAdolescents by Age Group —COVID-NET, June– November 2022\n051015202530\n<2 years 2–4 years 5–11 years 12–17 yearsWeighted % of hospitalizations\nAsthma Prematurity Feeding tube dependence\nObesity Chronic lung disease, not including asthma Immunocompromising condition\nGastrointenstinal/liver Disease Blood disorders Chronic lung disease of prematurity\nAutoimmune/inflammatory disease Abnormality of airway Diabetes\nData are limited to hospitalizations where COVID -19 is a likely primary reason for admission.10\nVaccination Status by Age Group among Non -Pregnant Adults \nAges ≥18 Years —COVID-NET, October– November 2022\nData are limited to hospitalizations where COVID -19 is a likely primary reason for admission. Unvaccinated: No recorded doses of COVID -19 vaccine. Vaccinated, but no bivalent booster: \nCompleted a primary series with or without ≥1 booster dose but did not receive an updated bivalent booster dose. Updated bivalent booster : Received updated bivalent booster dose. Partially \nvaccinated : Received at least one dose of COVID -19 but was not considered fully vaccinated at the time of a positive SARS -CoV-2 test. Pers ons with unknown vaccination status are excluded. 58.250.4\n34.1\n23.115.0 12.540.3\n42.4\n58.0\n66.9 79.676.55.42.73.42.78.0\n0%10%20%30%40%50%60%70%80%90%100%\n5–11 years 12–17 years 18–49 years 50–64 years 65–74 years ≥75 yearsPercent of hospitalizations\nUnvaccinated Vaccinated, but no bivalent booster Updated bivalent booster Partially vaccinated\n11\nMonthly Age-Adjusted Rates of Lab- Confirmed Hospitalizations by Vaccination Status \namong Adults Ages ≥18 Years —COVID- NET, January 2021–December 2022\n0100200300400500600700Rate per 100,000 population\nMonth of Admission\nUnvaccinated Primary series Primary series & ≥1 booster\nPrimary series & ≥2 boosters Vaccinated, no bivalent booster Updated bivalent booster\nData are based on all hospitalizations regardless of reason for admission. Unvaccinated : No recorded doses of COVID -19 vaccine. Primary series ± ≥1 booster: Completed a primary series with or without ≥1 \nbooster dose but did not receive an updated bivalent booster dose. Vaccinated, but no bivalent booster : Completed a primary series with or without ≥1 booster dose but did not receive an updated bivalent \nbooster dose. Updated bivalent booster : Received updated bivalent booster dose. Persons with partial or unknown vaccination status are excluded. See https://covid.cdc.gov/covid-data-tracker/#covidnet -\nhospitalizations-vaccination for complete definitions of vaccination categories. In December 2022, compared to adults \nwho received an updated bivalent booster dose, the monthly rates of hospitalization were-16x higher among unvaccinated and \n-2.6x higher in vaccinated adults without an updated booster dose.\n12\nAcknowledgments\nCoronaviruses and Other Respiratory \nViruses Division (CORVD) (proposed):\nRESP-NET Team (COVID -NET/RSV -NET):\n•Fiona Havers\n•Huong Pham\n•Michael Whitaker\n•Kadam Patel\n•Jenny M ilucky\n•Onika Anglin\n•Bhoomija C hatwani\nMany others in CORVD….State, Local, and Territorial h\nealth Department partners\nRESP- N ET partners\nThank you.\n\nFor more information, contact CDC\n1-800-CDC- INFO (232- 4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nT\nhe findings and conclusions in this report are those of the authors and do not necessarily represent the \nofficial position of the Centers for Disease Control and Prevention.", "summary": "National Center for Immunization & Respiratory Diseases Trends in COVID -19-Associated Hospitalizations —COVID -19-Associated  Hospitalization Surveillance Network (COVID -NET), March 2020–February 2023 Christopher A. Taylor, PhD Epidemiologist, COVID -NET Coronaviruses and Other Respiratory Viruses Division National Center for Immunizations and Respiratory DiseasesCenters for Disease Control and Prevention Advisory Committee on Immunization Practices February 24, 2023  Weekly Population-Based…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/COVID-06-Taylor-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 14}
{"title": "COVID 07 Britton 508", "content": "Centers for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.COVID -19 vaccine effectiveness updates\n24 February 2023\nAmadea Britton, MD, SM\nMedical Officer, Vaccine Effectiveness and Policy Team\nCenters for Disease Control and Prevention\nPreliminary vaccine effectiveness (VE) of monovalent vaccines against \nsymptomatic infection in children aged 6 months –4 years (Pfizer -BioNTech) \nand 6 months –5 years (Moderna)\nUpdate on VE of bivalent vaccines against symptomatic infection in children \nand adolescents aged 5 -17 years and adults aged ≥18 years\nUpdate on VE of bivalent vaccines against severe disease in adults with a \nfocus on adults aged ≥ 65 yearsOrganization of presentation\n2\nPreliminary Estimates of Effectiveness of mRNA Vaccines in \nPreventing Symptomatic SARS -CoV -2 Infection Among Children Aged 3 –5 \nYears —Increasing Community Access to Testing Program, United States, July \n2022 –February 2023\nFleming -Dutra KE, Ciesla AA, Roper, LE et al. Preliminary Estimates of Effectiveness of Monovalent mRNA Vaccines in Preventing Symptomatic SARS- CoV-2 Infection \nAmong Children Aged 3 –5 Years — Increasing Community Access to Testing Program, United States, July 2022 –February 2023. MMWR Morb Mortal Wkly Rep \n2023;72:177– 182. DOI: http://dx.doi.org/10.15585/mmwr.mm7207a3\n3\nAges 6 months –\n4 years\n(Primary Series:  \nPfizer -BioNTech)Primary Primary3–8 weeks\nPrimary\n***At least\n8 weeksAges 6 months –\n5 years\n(Primary Series: Moderna )PrimaryPrimary\n**4–8 weeksPediatric COVID-19 Vaccine Primary Series Schedule*:\nAges 6 months –5 years (Moderna) and 6 months–4 years (Pfizer -BioNTech)  \n*On June 18, 2022, ACIP issued interim recommendations for the use of the Moderna COVID -19 vaccine for children aged 6 months –5 years and for the Pfizer -BioNTech COVID- 19 vaccine for children aged 6 \nmonths –4 years. \n** As of December 9, 2022, children who received 2 doses of monovalent Moderna vaccine are recommended to receive a single bi valent booster dose at least 2 months after their last primary series dose.\n***As of December 9, 2022, children who received 2 doses of monovalent Pfizer -BioNTech vaccine primary series are recommended to receive a bivalent dose as their third dose.Earliest date for a child to\nhave a “complete series”=\nAugust 1, 2022\nEarliest date for a child \nto have a “complete \nseries”=\nSeptember 19, 2022\n4\nPercent of people receiving COVID-19 vaccine by age and date administered \n–United States, December 14, 2020 – February 15, 2023\nhttps://covid.cdc.gov/covid -data- tracker/#vaccination -demographics -trends 5\n\nNationwide community -b ased drive -through SARS-CoV -2 testing via pharmacies\nSelf- r eported vaccine history at time of registration for COVID -19 testing\nDesign : T est -negative, case -control analysis*\nPopulation: Immunocompetent children 3 –4 /5** years with ≥1 COVID -like symptom \nand nucleic acid amplification testing (NAAT)\nPeriod for analysis:\n•Tested: July 4, 2022*** –F ebruary 5, 2023, BA.4/BA.5 predominant period, but \nincludes XBBIncreasing Community Access to Testing (ICATT) Program: VE of monovalent\nCOVID -19 vaccines against symptomatic infection in children aged 3-5 years\n*Models adjusted for: age, gender, race, ethnicity, social vulnerability index and HHS region of the testing location, underlyin g conditions (presence versus absence), pharmacy \nchain conducting the test, local incidence (cases per 100,000 by individual county and state in the 7 days before test date), and date of testing.\n** ICATT testing is generally limited to children ages 3 and up.\n***Analysis start date depended on vaccine/dose number being analyzed: Pfizer and Moderna 1stdoses started 7/4/2022; Pfizer 2nddose started 7/25/2022; Moderna 2nddose \nstarted 8/1/2022; Pfizer 3rddose started 9/19/2022.6\nICATT: Preliminary estimates of VE for primary series monovalent Moderna vaccine \n(children aged 3– 5 years) against symptomatic infection , July 4, 2022 –February 5, 2023\n7Fleming -Dutra, Ciesla, Roper, et al. MMWR February 16, 2023.\n*Test registrants who report receiving COVID -19 vaccines are asked to report the total number of doses and manufacturer(s) of va ccines \nreceived and for the most recent dose, month and year of receipt; therefore, the number of months between a vaccine dose and tes ting is a \nwhole number calculated as the difference between the month and year of testing and the month and year of the vaccine dose. F or doses \nreceived in the same month or the month before SARS -CoV- 2 testing, an additional question was asked to specify whether the dose was \nreceived ≥2 weeks before testing, and only doses received ≥2 weeks before testing were included. 17% and 21% of children who received 1 \nand 2 doses of Moderna, respectively, reported a prior infection >90 days before the current test.Vaccination status (months since last dose)Total \ntestsSARS-CoV -2\npositive, N (%)Adjusted\nVE (95% CI)\nModerna, 1 dose (partial series; ages 3-5 years)\nJuly 4, 2022 –February 5, 2023\nUnvaccinated 34,982 9,523 (27) Ref\n1monovalent dose (2 weeks– 1 month)* 509 107 (21) 40 (26 to 52)\nModerna, 2 doses (complete series; ages 3-5 years)\nAugust 1, 2022 –February 5, 2023\nUnvaccinated 25,049 5,690 (23) Ref\n2 monovalent doses (2 weeks– 2 months)* 816 81 (10) 60 (49 to 68)\n2 monovalent doses (3 –4 months)* 495 58 (12) 36 (15 to 52)\n-20 0 20 40 60 80 100\nV accine E ffectiveness (%)\nICATT: Preliminary estimates of VE for primary series monovalent Pfizer -BioNTech vaccine \n(children aged 3– 4 years) against symptomatic infection , July 4, 2022 –February 5, 2023\n8Fleming -Dutra, Ciesla, Roper, et al. MMWR February 16, 2023.\n*Test registrants who report receiving COVID -19 vaccines are asked to report the total number of doses and manufacturer(s) of va ccines \nreceived and for the most recent dose, month and year of receipt; therefore, the number of months between a vaccine dose and tes ting is a \nwhole number calculated as the difference between the month and year of testing and the month and year of the vaccine dose. F or doses \nreceived in the same month or the month before SARS -CoV- 2 testing, an additional question was asked to specify whether the dose was \nreceived ≥2 weeks before testing, and only doses received ≥2 weeks before testing were included. 18%, 19% and 21% of children who \nreceived 1, 2, and 3 doses of Pfizer, respectively, reported a prior infection >90 days before the current test.\n**There was insufficient power to stratify Pfizer -BioNTech 3 -dose VE estimates by time since vaccination.Vaccination status (months since last dose)Total \ntestsSARS- CoV-2\npositive, N (%)Adjusted\nVE (95% CI)\nPfizer, 1 dose ( partial series; ages 3 –4 years)\nJuly 4, 2022 –February 5, 2023\nUnvaccinated 22,323 6,212 (28) Ref\n1 monovalent dose (2 weeks –1 month)* 443 114 (26) 19 (-1 to 35)\nPfizer, 2 doses ( partial series; ages 3 –4 years)\nJuly 25, 2022 –February 5, 2023\nUnvaccinated 17,434 4,298 (25) Ref\n2 monovalent doses (2 weeks– 3 months)* 933 137 (15) 40 (28 to 50)\nPfizer, 3 doses ( complete series; ages 3 –4 years)**\nSeptember 19, 2022 –February 5, 2023\nUnvaccinated 7,548 1,273 (17) Ref\n3 monovalent doses (2 weeks– 4 months)* 395 53 (13) 31 (7 to 49)\n-20 0 20 40 60 80 100\nV accine E ffectiveness (%)\nVaccine coverage is low in children ≤5 years. VE estimates may \nbe\n less stable when vaccine coverage is low. \nPrevalence of prior infection in children is hig h* ; consequently, \nvaccine effectiveness in this analysis reflects the current situation among young children in the United States.\nLow vaccination coverage in this age group may impact future a\nbility to estimate VE, including against more severe outcomes.Limitations\n*https://covid.cdc.gov/covid-data-tracker/#pediatric-seroprevalence.9\nComplete mo novalent primary vaccination series helped provide protection for \nchildren aged 3 –5 years against symptomatic SARS -CoV-2 infection for at least the \nfirst 4 months after vaccination.\nWaning of monovalent M oderna primary series might occur by 3 –4 months after the \nsecond dose based on point estimates (although confidence intervals overlapped). \nThis is similar to patterns observed in older children and adults in the first months \nafter vaccination. \n–Waning of monovalent Pfizer -B ioNTech VE against symptomatic infection could not be assessed but is also \nlikely based on analyses in older children and adults. \nChildren should stay up to date with COVID -1 9 vaccines, including completing the \nprimary series; those who are eligible should receive a bivalent vaccine dose.\nCDC will continue to monitor VE in this age group, including against severe disease an\nd for bivalent doses.Conclusions\n10\nUpdated estimates of VE against \nsymptomatic infection among children and \nadolescents aged 5– 17 and adults aged ≥18 \nyears\n11\nAbsolute VE: c omparing the frequency of health outcomes in vaccinated and \nunvaccinated people \n–\n–E.g., comparing outcomes in people vaccinated with an updated bivalent booster versus no \nvaccine at all\nRelative VE: c omparing the frequency of health outcomes in people who received \none type of vaccine to people who received a different vaccine or by comparing \npeople who received more vaccine doses to those who received fewer doses \nE.g., comparing outcomes in people vaccinated with an updated bivalent booster versus \nmonovalent vaccine only\nIn the analyses presented today, relative vaccine effectiveness can be interpreted as th\ne additional protection provided by an updated bivalent booster among people \nwho already received monovalent COVID -19 vaccinesInterpreting absolute and relative vaccine effectiveness \n12\nNationwide community- bas ed drive -through SARS-CoV -2 testing via pharmacies\nSelf-repo rted vaccine history at time of registration for COVID -19 testing\nDesign:  Test -negative, case -control analysis*\nPopulation :  Children and adolescents aged 5–17 years and adults aged ≥18 years with ≥1 COVID -like \nsymptom and nucleic acid amplification testing (NAAT)\nExclusion criteria: E xcluded individuals <4 months from last monovalent dose and individuals with \nimmunocompromising conditions\nPeriods for analysis:\n•Tested: December 1, 2022 –F ebruary 13, 2023**\n•Includes periods of both BA.5-rel ated sublineage and XBB/XBB.1.5 sublineage predominanceICATT: Relative VE of bivalent booster against symptomatic infection in \nchildren and adolescents aged 5 –17 years and adults aged ≥18 years\n*Models adjusted for: age, gender, race, ethnicity, social vulnerability index and HHS region of the testing location, underlyin g conditions (presence versus absence), local incidence (cases per 100,000 by individual county and \nstate in the 7 days before test date), and date of testing\n**Analysis is an update of data published in Link -Gelles R, Ciesla AA, Roper LE, et al. Early estimates of bivalent mRNA booster dose vaccine effectiveness in preventing symptomatic SARS -CoV- 2 infection attributable to SARS -\nCoV- 2 Omicron BA.5 -related and XBB/XBB.1.5 -related sublineages among immunocompetent adults —Increasing Community Access to Testing Program, United States, December 2022 –January 2023. MMWR Morb Mortal Wkly\nRep 2023;72.  https://www.cdc.gov/mmwr/volumes/72/wr/mm7205e2.htm13\nICATT: Relative VE of bivalent booster against symptomatic infection in children and \nadolescents aged 5– 17 years, December 1, 2022 –February 13, 2023*\n*Unpublished CDC data. 14Age group, years/mRNA Dosage PatternTotal\ntestsSARS-CoV -2 \npositive tests, Adjusted VE\nN (row %) (95% CI)\n5-11 years (authorized for bivalent booster \non October 12, 2022)\nReceived 2 -3monovalent doses only (Ref) 4,855 1,433 (30) Ref\n2 weeks -1 month since bivalent booster 600 73 (12) 65 (55 to 73)\n2-3 months since bivalent booster 881 139 (16) 54 (43 to 62)\n4-5 months since bivalent booster 58 10 (17) ----\n12-17 years (authorized for bivalent booster \non September 1, 2022)\nReceived 2 -3 monovalent doses only (Ref) 8,243 3,194 (39) Ref\n2 weeks -1 month since bivalent booster 443 73 (16) 68 (58 to 75)\n2-3 months since bivalent booster 1,122 230 (20) 56 (49 to 62)\n4-5 months since bivalent booster 283 68 (24) 53 (37 to 64)\n0 20 40 60 80 100\nVaccine Effectiveness %\nICATT: Relative VE of bivalent booster against symptomatic infection in adults aged \n≥18 years, December 1, 2022 –February 13, 2023*\n*Unpublished CDC data. 15Age group, years/mRNA Dosage PatternTotal\ntestsSARS- CoV-2 \npositive tests, Adjusted VE\nN (row %) (95% CI)\n18-49 years\nReceived 2 -3 monovalent doses only (Ref) 182,741 82,043 (45) Ref\n2 weeks -1 month since bivalent booster 10,758 3,127 (29) 51 (49 to 53)\n2-3 months since bivalent booster 32,577 10,206 (31) 45 (43 to 46)\n4-5 months since bivalent booster 9,197 2,882 (31) 41 (38 to 44)\n50-64 years\nReceived 2 -4 monovalen t doses only (Ref) 60,822 31,878 (52) Ref\n2 weeks -1 month since bivalent booster 6,223 2,331 (37) 46 (43 to 49)\n2-3 months since bivalent booster 18,399 7,898 (43) 32 (29 to 34)\n4-5 months since bivalent booster 4,837 2,030 (42) 28 (23 to 32)\n≥65 years\nReceived 2 -4 monovalent doses only (Ref) 28,307 14,246 (50) Ref\n2 weeks -1 month since bivalent booster 4,579 1,788 (39) 38 (34 to 42)\n2-3 months since bivalent booster 19,071 8,080 (42) 27 (25 to 30)\n4-5 months since bivalent booster 5,796 2,431 (42) 21 (16 to 26)\n0 20 40 60 80 100\nVaccine Effectiveness %\nUpdated estimates of VE against \nemergency department/urgent care encounters \nand hospitalizations among adults aged ≥18 years, VISION Network\nVISION Multi -State Network of Electronic Health Records\nVariant periods designated for \nanalysis based on time when novel sublineage became predominant at \nstudy site\nVE a djusted for age, sex, race, \nethnicity, geographic region, calendar time, and local rates of SARS -CoV -2 circulation\nVaccination documented by electronic health records and state and city registriesCases : COVID -like illness (CLI) with \npositive PCR for SARS- CoV-2 within 14 \ndays before or 72 hours after the \nadmission or encounter\nControls : CLI with negative PCR for SARS-\nCoV-2\n 17\nmRNA Dosage PatternTotal \ntestsSARS- CoV-2-\ntest-positive,\nN (%)Median interval\nsince last dose,\ndays (IQR)Adjusted VE\n(95% CI)\nEmergency department/urgent care encounters\nAged 18 -64 years\nUnvaccinated (Ref) 56,560 6,632 (12) — Ref\nMonovalent doses only, last dose ≥2 months earlier 79,203 8,848 (11) 370 (300- 508) 2 (-2 to 5)\nAged ≥65 years\nUnvaccinated (Ref) 11,277 2,026 (18) — Ref\nMonovalent doses only, last doses ≥2 months earlier 37,505 5,588 (15) 335 (196- 424) 12 (6 to 17)\nHospitalizations\nAged 18 -64 years\nUnvaccinated (Ref) 6,213 475 (8) — Ref\nMonovalent doses only, last doses ≥2 months earlier 7,250 501 (7) 360 (281- 502) 19 (7 to 30)\nAged ≥65 years\nUnvaccinated (Ref) 4,795 819 (17) — Ref\nMonovalent doses only, last doses ≥2 months earlier 14,462 1924 (13) 337 (205- 439) 28 (22 to 34)VISION: Absolute VE of ≥2monovalent doses against ED/UC encounters and \nhospitalizations among adults aged ≥18 years –September 2022 –January \n2023*\n*Unpublished CDC data.-20 0 20 40 60 80 100\nVaccine Effectiveness (%)\n18\nVISION: Relative VE of bivalent booster against ED/UC encounters and \nhospitalizations among adults aged ≥18 years –September 2022 –January \n2023*\n*Unpublished CDC data. 19mRNA Dosage Pattern Total testsSARS -CoV-2-\ntest-positive,\nN (%)Median \ninterval\nsince last \ndose,\ndays (IQR)Adjusted VE\n(95% CI)\nEmergency department/urgent care encounters\nMonovalent doses only, last dose ≥2 months earlier 112,857 13,429 (12) 359 (279- 496) Ref\nBivalent booster, 7 -59 days earlier 12,546 948 (8) 33 (20 -46) 50 (46 to 53)\nBivalent booster, 60 -119 days earlier 5,952 617 (10) 76 (67 -87) 36 (30 to 41)\nHospitalizations\nMonovalent doses only, last dose ≥2 months earlier 28,227 3,187 (11) 348 (243- 484) Ref\nBivalent booster, 7 -59 days earlier 2,809 202 (7) 32 (19 -45) 52 (44 to 58)\nBivalent booster, 60 -119 days earlier 1,281 155 (12) 74 (67 -85) 31 (18 to 42)\n0 20 40 60 80 100\nVaccine Effectiveness (%)\nPreliminary estimates of VE against \nhospitalizations among adults aged ≥65 years, \nIVY Network\nIVY Network —24 hospitals, 19 U.S. States\nDesign : P rospective test-negative, case -control\nPeriod :  September 8, 2022 –January 30, 2023\nPopulation: Immunocompetent adults\nh\nospitalized with COVID -like illness (CLI)\nParticipants have CLI and SARS-C oV-2 test:\n–\n–Cases: S ARS -CoV-2-positive by RT -PCR or \nantigen\nControls: S ARS -CoV-2-and influenza- negative \nby RT -PCR\nVE adjustments: Ag e, sex, race/ethnicity, \nadmission date (biweekly), and HHS region\n21\nVaccinated \ncases, \nN/total cases \n(%)Vaccinated \ncontrols, \nN/total \ncontrols      \n(%)Median \ninterval\nsince last \ndose,\ndays (IQR)Adjusted \nVE,\n% (95% CI)\nAbsolute monovalent VE against hospitalization \nUnvaccinated (Ref) -- Ref\n≥2 Monovalent doses, last dose ≥2 months earlier 550/707 (78) 645/810 (80) 352 (224- 432) 17 (- 7 to 36)\nRelative bivalent VE against hospitalization \n≥2 Monovalent doses, last dose ≥2 months earlier (Ref) 352 (224- 432) Ref\nBivalent booster dose, ≥7 days earlier 108/658 (16) 255/900 (28) 56 (30 –84) 52 (37– 64)\nAbsolute bivalent VE against hospitalization \nUnvaccinated (Ref) -- Ref\nBivalent booster dose, ≥ 7 days earlier 108/265 (41) 255/420 (61) 56 (30 –84) 55 (36– 69)IVY: Absolute VE of ≥2 monovalent doses and relative VE of bivalent booster against \nCOVID -19 hospitalizations among adults aged ≥65 years —IVY Network, September 8, \n2022– January 30, 2023*\n*Unpublished CDC data.-20 0 20 40 60 80 100\nVaccine Effectiveness (%)\n22\nVaccinated \ncases, \nN/total cases \n(%)Vaccinated \ncontrols, \nN/total \ncontrols      \n(%)Median \ninterval\nsince last \ndose,\ndays (IQR)Adjusted \nVE,\n% (95% CI)\nAbsolute monovalent VE against hospitalization \nUnvaccinated (Ref) -- Ref\n≥2 Monovalent doses, last dose ≥2 months earlier 550/707 (78) 645/810 (80) 352 (224- 432) 17 (- 7 to 36)\nRelative bivalent VE against hospitalization \n≥2 Monovalent doses, last dose ≥2 months earlier (Ref) 352 (224- 432) Ref\nBivalent booster dose, ≥7 days earlier 108/658 (16) 255/900 (28) 56 (30 –84) 52 (37– 64)\nAbsolute bivalent VE against hospitalization \nUnvaccinated (Ref) -- Ref\nBivalent booster dose, ≥7 days earlier 108/265 (41) 255/420 (61) 56 (30 –84) 55 (36– 69)IVY: Absolute VE of ≥2 monovalent doses and relative VE of bivalent booster against \nCOVID -19 hospitalizations among adults aged ≥65 years —IVY Network, September 8, \n2022– January 30, 2023*\n*Unpublished CDC data.-20 0 20 40 60 80 100\nVaccine Effectiveness (%)\n23\nIVY: Severity of COVID-19 hospitalizations in bivalent booster VE analysis among \nadults aged ≥65 years —IVY Network, September 8, 2022–January 30, 2023*\nCharacteristicCase -patients, N (%)\nN = 719**\nHypoxemia 427 (59)\nHigh flow nasal cannula (HFNC) 78 (11)\nNon -invasive positive pressure ventilation (NIPV) 51 (7)\nInvasive mechanical ventilation (IMV) 47 (7)\nHFNC, NIPPV, or IMV 138 (19)\nICU admission 116 (16)\nIn-hospital death on or before Day 28 38 (5)\n*Unpublished CDC data.\n**Data missing for 12% (96/815) of cases due to reporting lag.•Of all hospitalized cases, 59% had documented hypoxemia\n•Approximately 16% of hospitalized cases required an ICU admission\n•Some hospitalizations included in the analysis may not represent severe COVID -19 disease \n24\nConclusions\nFor estimates of absolute v accine effectiveness, if unvaccinated or vaccinated \nindividuals are significantly different than the rest of the population, estimates may \nbe biased.\nFor estimates of relative v accine effectiveness, residual protection from prior doses is \nan important consideration.\n–\n–Particularly important for severe disease, for which residual protection from prior doses may be higherCan be challenging to interpret waning of relative VE\nLimited information on prior infection, although we know rates of prior infection in \nt\nhe U.S. population are high. \nVE against COVID -1 9 associated hospitalization may underestimate protection against \nsevere COVID -19 disease.Limitations\n26\nUpdates to VE of bivalent C OVID -19 booster against symptomatic infection \namong children and adolescents aged 5-17 years and adults aged ≥18 years \n–\n–Bivalent booster provided added protection, though early evidence of \nwaning of relative effectiveness\nUpdates to VE of bivalent C OVID -19 booster against ED/UC encounters and \nhospitalizations among adults ≥18 years\nBivalent boosters are helping provide additional protection against e\nmergency department/urgent care encounters and hospitalization\n–For most people who received monovalent doses and are eligible for a bivalent booster, more than a year has elapsed since their last monovalent dose. Because of waning, they may have limited remaining protection.Conclusions\n27\nCDC COVID- 19 Vaccine Effectiveness and \nPolicy Team\nAllison Ciesla\nMonica Godfrey\nKatherine Fleming -Dutr a\nRuth Link- G elles\nMorgan Najdowski\nSara Oliver\nAmanda Payne\nLauren Roper\nLaura Steinhardt\nEvelyn Twentyman\nMegan Wallace\nRyan WiegandPIs and study staff for VE platforms\nSarah Ball\nJennifer DeCuir\nMonica Dickerson\nMargaret Dunne\nEric Griggs\nMatthew Levy\nPatrick Mitchell\nPalak PatelAcknowledgements\n28Sarah Reese\nHeather Scobie\nZach Smith\nDiya Surie\nZack Weber\nMark Tenforde\nFor more information, contact CDC\n1-800-CDC- INFO (232- 4636)\nTTY:  1 -888- 232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position o f the Centers for Disease Control and Prevention.\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation use. No rights are implied or extended for use in printing or \nany use by other CDC CIOs or any external audiences.", "summary": "Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/COVID-07-Britton-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 29}
{"title": "COVID 08 Oliver 508", "content": "cdc.gov/coronavirus\nConsiderations for Bivalent Primary Series \nSara Oliver, MD, MSPH\nACIP MeetingFebruary 24, 2023\nDoes ACIP support h armonizing the vaccine strain composition for mRNA COVID- 19 \nvaccines across both primary series and booster doses:\nChanging the primary series from monovalent (Original) to bivalent (Original plus Omicron \nBA.4/5) for all ages?Question for consideration\n2Mono-\nvalent Mono-\nvalent BivalentPeople ages 6 months and older*\nBivalent Bivalent BivalentPeople ages 6 months and older*Current recommendations \n(Simplified representation)Future proposed recommendations\n*Ages and vaccines as authorized by FDA and recommended by ACIP/CDC\nFor children ages 6 months -4 years of age who start a Pfizer -BioNTech \nprimary series, 3- dose primary series still needed*Ages and vaccines as authorized by FDA and recommended by ACIP/CDC\nFor children ages 6 months -4 years of age who start a Pfizer -BioNTech \nprimary series, the third dose in a 3 -dose primary series is a bivalent doseBooster dose\n(in most ages) Primary seriesBooster dose\n(in most ages) Primary series\nPolicy considerations for bivalent primary series\n3Policy on bivalent primary series will be coordinated with F DAfor \nregulatory action, and CDC/ACIP for recommendations for use \nReview data \nDiscuss \nconsiderations FDA\nRegulatory   \nallowanceCDC/ACIP\nRecommendations \nfor use\n4Public \nHealth \nProblemConsiderations for Bivalent Primary Series  \nCoverage / Age (years) <2 2–4 5–11 12–17 18–24 24–49 50–64 >65\nAt least 1- dose 7.6 10.3 39.7 71.9 81.9 85.2 95.0 95.0\nCompleted primary series 3.7 5.5 32.6 61.6 66.5 72.0 83.7 94.2\n1st monovalent booster* - - 3.3 16.6 27.2 45.3 64.6\n2nd monovalent booster * - - - - - - 10.6 25.3\nBivalent booster** 0.2 0.3 4.0 7.0 6.7 11.2 20.3 40.8\nUnvaccinated 92.4 89.7 60.3 28.1 18.1 14.8 —†—†U.S. COVID-19 Vaccination Coverage (%) of Total Population by \nAge Group — February 8, 2023\n*Monovalent booster dose coverage as of August 26, 2022\n** Bivalent booster coverage is independent of 1stand 2nddose monovalent coverage\n†Note: Coverage is capped at 95%\nSource: https://covid.cdc.gov/covid -data -tracker/#vaccination -demographics -trends Updated February 10, 2023 5\nGray boxes indicate potential reporting delays. Interpretation of trends should be excluded from these weeks. Weekly Population -Based Rates of COVID -19-Associated Hospitalizations among \nChildren and Adolescents Ages ≤17 Years —COVID- NET, March 2020 –February 2023\n01020304050607080Rate per 100,000 population\nWeek Ending DateAugust 2022– February 2023\n01020304050607080Rate per 100,000 population\nWeek Ending DateMarch 2020 –February 2023 (entire pandemic period)\n<6 months 6 months–<2 years 2–4 years 5–11 years 12–17 years\nGray boxes indicate potential reporting delays. Interpretation of trends should be excluded from these weeks. \nUnderlying Medical Conditions among Children and Adolescents Ages ≤17 Years \n—COVID -NET, June –November 2022\n13.1\n11.2\n8.8 8.8\n7.9\n6.7 6.6 6.4\n5.3\n3.5 3.4\n2.62.2\n02468101214Weighted % of hospitalizations\nData are limited to hospitalizations where COVID -19 is a likely primary reason for admission.49% of hospitalized children and \nadolescents have no underlying \nmedical conditions .\nAge-adjusted rates of COVID -19-associated hospitalization by vaccination status and \nreceipt of booster dose in children and adolescents\nCOVID -NET, December 2021 -December 2022\nCDC COVID Data Tracker. https://covid.cdc.gov/covid -data -tracker/#covidnet -hospitalizations -vaccination Accessed February 10, 2023 8\nHospitalization rates by vaccination status\nAdolescents ages 12 -17 years\nHospitalization rates by vaccination status\nChildren ages 5 -11 years\n050100150200250300\n0-5\nmonths6-11\nmonths1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17COVID -19 deaths\nAge in yearsCOVID -19 deaths in children and adolescents by age based on death certificate \ndata, National Center for Health Statistics\nJanuary 1, 2020– February 11, 2023\nSource: https://data.cdc.gov/NCHS/Provisional -COVID -19-Deaths-Counts- by-Age-in-Years/3apk -4u4f/data. Accessed February 16 , 2023  Children 6 months –17 years : \n1489 COVID -19 deaths\n1.4% of all deaths in this age group\nDeath rates by vaccination status and receipt of bivalent booster doses among \npeople ages 5 years and older April 3 –December 3, 2022 (23 U.S. Jurisdictions)\n*Includes either a booster or additional dose.    Updated booster = Bivalent booster \nCDC COVID Data Tracker. https://covid.cdc.gov/covid -data -tracker/#rates -by-vaccine- status Accessed February 10, 2023In November 2022, people ages \n5 years and older with \nbivalent booster had \n12.7 times lower risk of dying \nfrom COVID -19, compared \nto unvaccinated people and \n2.4 times lower risk of dying from \nCOVID-19 than people \nvaccinated without \na bivalent booster\n10\n\nChildren and adolescents can develop severe COVID- 19. Nearly 1500 children and \nadolescents have died from COVID- 19 since the beginning of the pandemic\nHalf of the hospitalized children and adolescents had no underlying medical \nconditions \nDuring all periods, COVID- 19 hospitalizations and mortality were consistently higher\namong unvaccinated persons than among persons who had completed a primary \nseries and/or an updated booster\nMany children remain unvaccinated for COVID- 19Considerations for Bivalent Primary Series \nPublic Health Problem \nBenefits \nand \nHarmsConsiderations for Bivalent Primary Series\n12\nOngoing, Phase 3, open- l abel study (unpublished, data obtained from sponsor)\nChildren ages 6 months –5 y ears in United States\n–\n–Original primary series (historical control):  4,792 participants received 25 ug of \nm\nRNA- 1273\nBA.1 bivalent primary series: 179 participants received 25 ug of mRNA -1 273.214 \n(12.5 ug original strain and 12.5 ug Omicron BA.1 strain) \nMedian follow- up f or the original vaccine was 102 days post Dose 1 and for the BA.1 \nbivalent vaccine was 85 days post Dose 1  \nBaseline SAR -Co V-2 positive was 8% for the original vaccine and 63% for the BA.1 \nbivalent vaccineModerna BA.1 bivalent primary series among children \nages 6 months –5 years \n13\nImmunogenicity of Moderna BA.1 bivalent primary series \namong children ages 6 months –5 years \n14Bivalent Vaccine Original Vaccine\nOutcome Time point NGMTa(95% CI)N GMTa(95% CI)GMRb(95% CI) –\nBivalent vs. Original\nBA.1 \nNeutralizing AntibodyPre Dose 1\n5849.2 (30.4, 79.6)\n4025.9 (5.5, 6.2)\nDay 57 1889.7 (1430.0, 2497.2) 74.3 (67.7, 81.7) 25.42 (20.14, 32.07)\nc\nOriginal Strain Neutralizing AntibodyPre Dose 1\n6635.6 (24.0, 52.7)\n5949.6 (8.9, 10.4)\nDay 57 1432.9 (1054.5, 1947.0) 1732.5 (1611.5, 1862.5) 0.83 (0.67, 1.02)\nd\nGMT = geometric mean titer; GMR = geometric mean ratio; CI=confidence interval\na  GMTs were estimated using an analysis of covariance (ANCOVA) model with neutralizing antibody values at Day 57 as the depend \nvariable and a group variable (mRNA -1273.214 vs mRNA -1273) as the fixed variable, adjusted by age group and by baseline SARS -CoV- 2 \ninfection status. The GMT value at Day 57 was estimated by the geometric least square mean (GLSM) from the model.\nb  GMRs were estimated by the ratio of the GLSMs with a 2- sided 95% CI from the model\nc Met the pre -specified superiority success criterion (lower bound of the 95% CI > 1.0)\nd Met the pre -specified non- inferiority success criterion (lower bound of the 95% CI > 0.667)\n142 patients received two doses of the bivalent vaccine\nPercentage of patients reporting solicited local or systemic events was similar to or \nless than percentages seen after original vaccine, however this may be a result of the \nlarger percent of seropositive participants in the bivalent vaccine group\nPain, axillary (or groin) swelling or tenderness, and erythema were the most common local events\nIrritability/crying, sleepiness, and fatigue were the most common systemic events\nThere were no Grade 4 solicited adverse events reported\nThere was one serious adverse events (SAE) of asthma exacerbation reported after the first dose that was assessed as unrelated to vaccination by the investigatorSafety of Moderna BA.1 bivalent primary series among children ages 6 months –5 years \nSafety of Moderna BA.1 bivalent primary series among \nchildren ages 6 months –5 years \nFrom Jan 26, 2022 VRBPAC meeting : https://www.fda.gov/media/164810/download\nSafety of Moderna BA.1 bivalent primary series among \nchildren ages 6 months –5 years \nFrom Jan 26, 2022 VRBPAC meeting : https://www.fda.gov/media/164810/download\nSystemic reactions   6 –36months\nSystemic reactions   37 months –5 years\nConcern that initial exposure to one virus strain may primes B -c ell memory and limit the \ndevelopment of memory B cells and neutralizing antibodies against new strains\nPrior infection and/or vaccine history likely has impact on subsequent immune response1-3\nAffinity maturation oc curs: the ability of memory B cells to mature over time, especially \nwhen exposed to newer strains4-5\n–Variant -s pecific vaccines can also initiate new variant -specific immune responses6-7\nClinical impact of different immune responses by prior exposure, or how it may differ by \ni\nnfection and vaccine, requires additional research\nVaccines continue to be able to provide a b road boost in antibody responses \nImprinting concerns related to in cremental benefit of updated variant- specific vaccinesConsiderations for Bivalent Primary Series: \nImprinting\n1.Immune boosting by B.1.1.529 (Omicron) depends on previous SARS -CoV-2 exposure | Science\n2.Imprinted SARS -CoV-2 humoral immunity induces convergent Omicron RBD evolution (nature.com)\n3.Protective Effect of Previous SARS -CoV-2 Infection against Omicron BA.4 and BA.5 Subvariants | NEJM\n4.Affinity maturation of SARS -CoV-2 neutralizing antibodies confers potency, breadth, and resilience to viral escape mutations – ScienceDirect 185.The germinal centre B cell response to SARS-CoV -2 | Nature Reviews Immunology\n6.SARS -CoV-2 Omicron boosting induces de novo B cell response in humans | bioRxiv\n7.Molecular fate -mapping of serum antibody responses to repeat immunization (nature.com)\nSeveral studies compared antibody titers with recent Omicron sub- l ineages for both the bivalent \nand monovalent vaccines; most studies ranging from ~21 -42 days after bivalent vaccine\nRatio o f antibody titers from bivalent vaccine to monovalent vaccine shownComparing monovalent and bivalent vaccines\nAntibody data\n1. https://www.biorxiv.org/content/10.1101/2022.10.22.513349v1.full.pdf\n2. https://www.nejm.org/doi/full/10.1056/NEJMc2213948\n3. https://www.nejm.org/doi/full/10.1056/NEJMc2214314\n4. https://www.biorxiv.org/content/10.1101/2022.10.31.514636v1\n5. https://www.nature.com/articles/s41591 -022- 02162-x19Wang, et al1Collier, et al2 Davis -Gardner4 Kurhade, et al5 Miller, et al3012345678910\nBA.4/5 BA.4/5 XBB.1 BA.4/5 XBB.1Bivalent to Monovalent Ratio of Antibody Titers\nPseudovirus neutralization assays Live virus neutralization assaysOverall, most studies show improvement \ni\nn neutralizing antibodies for Omicron \nsub- lineages with a bivalent vaccine \n(ratio >1 )\nClinical impact is unknown for specific r\natios or antibody levels \nNeutralizing antibodies at a single time do no\nt convey the entire immune response\nUnable to directly compare clinical outcomes for monovalent and bivalent vaccines in \nthe\n U.S. due to timing of authorizations Comparing monovalent and bivalent vaccines\nClinical data\nhttps://www.fda.gov/media/164810/download\nA Randomized Trial Comparing Omicron -Containing Boosters with the Original Covid -19 Vaccine mRNA -1273 | medRxiv 20\nStudy in the UK found ~1 0% \nincrease in relative VE for COVID- 19 \ninfections \nUnable to estimate differential i\nmpact for prevention of severe \nCOVID -19\nConsiderations for Bivalent Primary Series \nBenefits and Harms \n21Bivalent COVID-1 9 vaccines are able to induce an immune response when given \neither as a primary series or a booster dose\nLimited data to directly compare COVID -19  outcomes after receipt of a \nmonovalent or bivalent vaccine \nCOVID -1 9 vaccines have a high degree of safety. Initial safety data from bivalent \nprimary series trial are encouraging but study was not powered to assess rare adverse events\n22Feasibility \nand \nImplementationConsiderations for Bivalent Primary Series\nNumber of mRNA COVID-19 vaccine products currently\nModerna: 5 products Pfizer- BioNTech: 6 products \n11 TOTAL Products!\n\nPossible number of mRNA COVID-19 vaccine products with a \nbivalent primary series\nModerna: 2 products Pfizer- BioNTech: 3 products \nCould be reduced to \n5 total products\nWould eliminates look -alike vials for \nModerna and Pfizer-BioNTech\nTransition to bivalent primary series could: \nImprove s torage space\n–\n–\n–\n–\n–Providers have limited storage space\nIn addition to monovalent and bivalent products, Vaccines for Children (VFC) stock required \nt\no be duplicate and separate\nReduce errors\nWould eliminate ‘look -alike’ vials\nCurrently, one of the most common administration errors reported is providers giving a bi\nvalent vaccine as a primary series\nAllow for c ontinued access to primary series\nMajority of current monovalent vaccine stock expires within the next few monthsConsiderations for Bivalent Primary Series  \nFeasibility and Implementation \n25\nWork is ongoing to evaluate cost effectiveness in preparation for a transition to \ncommercialization of COVID -19 vaccine \nBivalent COVID- 19 vaccines already purchased and delivered; transition of current \nprimary series recommendations from monovalent to bivalent vaccines unlikely to have significant impact on resource useConsiderations for Bivalent Primary Series \nResource Use \nSummary \nConsiderations for Bivalent Primary Series  \nSummary\n28Receiving a C OVID- 19 vaccine primary series continues to be important for \nprevention of COVID- 19 severe disease, hospitalization, and death\nMany children and adolescents remain unvaccinated for COVID- 1 9\nCOVID -19 vaccines recommendations that are simple to implement may remove \nsome barriers to uptake\nHarmonizing the primary series and booster doses could simplify the presentations, \nr\neduce administration errors, and allow continued access to primary series for \nunvaccinated populations\nThe Work Group was su pportive of a transition of the mRNA COVID- 19 vaccine \nprimary series from monovalent (original) to bivalent (original plus Omicron BA.4/5)\nMonica Godfrey\nMegan Wallace \nDanielle Moulia\nEvelyn Twentyman\nHannah Rosenblum\nLauren Roper\nKatherine Fleming-Dutra\nSarah Meyer\nSusan Goldstein\nMary Chamberland\nElisha Hall\nJulianne Gee\nValerie Morelli\nJoEllen WolickiHeather Scobie\nRuth Link - Gelles\nMegan Lindley\nSierra Scarbrough\nJefferson Jones\nAron Hall\nBarbara Mahon\nData Analytics and Visualization Task Force\nCoronavirus and other Respiratory Viruses Division\nNational Center for Immunization and Respiratory \nD\niseasesAcknowledgments\nQuestion for ACIP\n30Transition to bivalent primary series can only occur after FDA regulatory action \nan\nd updates to CDC recommendations \nWhat are ACIP thoughts on a tr ansition of the mRNA COVID- 19 vaccine primary \nseries from monovalent (original) to bivalent (original plus Omicron BA.4/5)?\nNote : “Monovalent” and “bivalent” designations are based on the currently authorized products. \nFor future vaccines, focus would be harmonization of products across primary series and booster doses. \nFor more information, contact CDC\n1-800-CDC- INFO (232- 4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.\nThank you\nComparing monovalent and bivalent vaccines\nAntibody data\n1. https://www.biorxiv.org/content/10.1101/2022.10.22.513349v1.full.pdf\n2. https://www.nejm.org/doi/full/10.1056/NEJMc2213948\n3. https://www.nejm.org/doi/full/10.1056/NEJMc2214314\n4. https://www.biorxiv.org/content/10.1101/2022.10.31.514636v1\n5. https://www.nature.com/articles/s41591 -022-02162 -x\n32Pseudovirus neutralization assayBivalent BA.4/BA.5\nN=19Monovalent\nN=21Ratio\nAncestral SARS -CoV -2 antibody titers (ID50) 8488 12054 0.70\nBA.4/BA.5 neutralizing antibody titers (ID50) 1649 1366 1.2\nPseudovirus neutralization assayBivalent BA.4/BA.5\nN=15Monovalent\nN=18Ratio\nAncestral SARS -CoV -2 antibody titers (ID50) 40575 21507 1.89\nBA.4/BA.5 neutralizing antibody titers (ID50) 3693 2829 1.31\nLive virus neutralization assayBivalent BA.4/BA.5\nN=12Monovalent\nN=12Ratio\nAncestral SARS -CoV -2 antibody titers (ID50) 2312 1812 1.27\nBA.5 neutralizing antibody titers (ID50) 576 142 4.06\nLive virus neutralization assayBivalent BA.4/BA.5\nWITH infection\nN=23Monovalent\nN=25Ratio\nAncestral SARS -CoV -2 antibody titers (ID50) 5776 1533 3.77\nBA.4/BA.5 neutralizing antibody titers (ID50) 1558 95 16.4\nXBB.1 neutralizing antibody titers (ID50) 103 15 8.58Wang, et al1\nCollier, et al2\nDavis -Gardner, et al4\nKurhade , et al5Pseudovirus neutralization assayBivalent BA.4/BA.5\nN=15Monovalent\nN=18Ratio\nAncestral SARS -CoV -2 antibody titers (ID50) 40515 21507 1.89\nXBB.1 neutralizing antibody titers (ID50) 170 175 0.97Miller, et al3References for data: \nLive virus neutralization assayBivalent BA.4/BA.5\nWithout infection\nN=29Monovalent\nN=25Ratio\nAncestral SARS -CoV -2 antibody titers (ID50) 3620 1533 2.36\nBA.4/BA.5 neutralizing antibody titers (ID50) 298 95 3.14\nXBB.1 neutralizing antibody titers (ID50) 35 15 2.33Antibody titers measured 24 -26 days after vaccine\nAntibody titers measured ~21 days post- dose for bivalent and ~32 days post- dose for monovalent group \nTiming post -vaccine differed (monovalent: 70 -100 days post vaccine; bivalent: 16 -42 days post vaccine) Antibody titers measured ~21 days post- dose for bivalent and ~32 days post- dose for monovalent group \nAntibody titers measured at different time points (monovalent: 23 -94 days post vaccine; bivalent: 14 -32 days post vaccine)", "summary": "cdc.gov/coronavirus Considerations for Bivalent Primary Series  Sara Oliver, MD, MSPH ACIP MeetingFebruary 24, 2023 Does ACIP support h armonizing the vaccine strain composition for mRNA COVID- 19  vaccines across both primary series and booster doses: Changing the primary series from monovalent (Original) to bivalent (Original plus Omicron  BA.4/5) for all ages?Question for consideration 2Mono- valent Mono- valent BivalentPeople ages 6 months and older* Bivalent Bivalent BivalentPeople ages…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/COVID-08-Oliver-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 32}
{"title": "COVID 09 Wallace 508", "content": "Centers for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nCenters for Disease Control and Prevention\nNational Center for Immunization and Respiratory Diseases\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation use. No rights are implied or extended for use in printing or any use by other CDC CIOs or any external audiences.Benefit and risk assessment for COVID -19 vaccines\nMegan Wallace, DrPH, MPH\nBenefit -risk assessment \n2Benefits of COVID- 19 vaccine by age for primary series \nIncremental benefits of COVID- 19 vaccine by age and time since last dose for \nbivalent booster dose\n–Sensitivity analyses model high and low points in the pandemic\nBenefit -risk assessment for bivalent booster dose\n–Focused on ages 12 -17 years and 18- 49 years\nMethods for benefit assessment\n3Benefits –Calculated per 1 million primary series or bivalent booster doses\nHospitalization rates1: December 2022 COVID -19-associated hospitalization rate among persons \naged 5 –11, 12–17, 18– 49, 50– 65, 65+ years, by vaccination status, from COVID-NET\n–Sensitivity analyses model high and low points in the pandemic\nTime horizon2: 6 months\nVaccine Effectiveness : VE estimates from VISION3with assumption of waning of effectiveness \nby 10% each month starting after month 2\n–VE of primary series based on absolute VE for bivalent dose4\n–VE of bivalent booster dose based on relative VE by interval from last monovalent dose to \nbivalent5\n1https://covid.cdc.gov/covid -data -tracker/#covidnet- hospitalizations -vaccination. Rates among unvaccinated used for primary serie s assessment. Rates among those vaccinated with \nmonovalent doses only used for bivalent booster dose assessment. \n2Period over which benefits of bivalent vaccination accrue \n3https://www.cdc.gov/mmwr/volumes/71/wr/mm715152e1.htm?s_cid=mm715152e1_w. \n4Absolute VE of bivalent booster dose (57%) used as the estimated primary series VE. Absolute VE from the bivalent booster was used as an estimate of primary series VE because current VE of \nmonovalent primary series is unknown. \n5Relative VE of bivalent booster dose used in booster dose assessment (5 -7 month interval: 38%; 8- 10 month interval: 42%; 11+ mon th interval 45%). Relative VE for ED/UC visit was used for 2 -4 \nmonth interval (31%) because VE against hospitalization was not available  \nMonthly age-adjusted rates of COVID-19-associated hospitalization \nby vaccination status in patients ≥ 18 years, COVID-NET\nhttps://covid.cdc.gov/covid -data -tracker/#covidnet- hospitalizations -vaccination\n4Age group Rate per 100,000 \npersons\n5-11 Years 2.13\n12-17 Years 2.66\n18-49 Years 12.89\n50-64 Years 27.48\n≥ 65 Years 121.10December 2022 hospitalization rates per \n100,000 vaccinated persons with no \nbivalent booster by age group, COVID- NET\n\nEstimated COVID -19-associated hospitalizations prevented over 6 \nmonths for every million mRNA COVID-19 primary series given \n248\n944\n2465\n5033\n15978\n0 2000 4000 6000 8000 10000 12000 14000 16000 18000COVID -19-associated hospitalizations p revented over 6 months per m illion doses by age group\nBased on hospitalization rates from December 2022\n12 –17 years\n18 –49 years\n50 –64 years\n≥ 65 years\n55 –11 years\nEstimated COVID -19 hospitalizations prevented over 6 months for \nevery million mRNA COVID -19 primary series and bivalent booster doses1\n53\n257\n549\n2419944\n2465\n5033\n15978\n0 2000 4000 6000 8000 10000 12000 14000 16000 18000COVID -19-associated hospitalizations p revented over 6 months per million\nprimary series or bivalent booster by age group\nBased on hospitalization rates from December 2022\n12 –17 years\n18 –49 years\n50 –64 years\n≥ 65 years\n1. Calculated assuming booster dose given ≥11 months from last monovalent vaccine dose 6\nEstimated COVID -19 hospitalizations prevented over 6 months for \nevery million bivalent mRNA COVID -19 booster doses, by age group and \ndose interval1\n0 500 1000 1500 2000 2500 3000COVID -19-associated hospitalizations p revented over 6 months per million doses given in \n2 –4 month interval, 5 –7 month interval, 8 –10 month interval, ≥11 month interval\nBased on hospitalization rates from December 2022\n12 –17 years\n18 –49 years\n50 –64 years\n≥ 65 years\n7 1Interval refers to the time between the most recent monovalent dose and a bivalent dose. \nMonthly age -adjusted rates of COVID -19-associated hospitalization \nby vaccination status in patients 12 – 17 years, COVID -NET\nhttps://covid.cdc.gov/covid -data -tracker/#covidnet- hospitalizations -vaccinationHigh\nLowRecent\n8\n\nEstimated COVID -19 hospitalizations prevented over 6 months for \nevery million bivalent mRNA COVID -19 booster doses, 12 –17-year -olds\n0 20 40 60 80 100 120 140 160COVID -19-associated hospitalizations p revented over 6 months per million\ndoses by low, recent , and high incidence1\n2-5 month interval2\n5-7 month interval2\n8-10 month interval2\n11+ month interval2\n91Low incidence scenario uses hospitalization rate from March 2022, recent incidence scenario uses hospitalization rate from De cem ber 2022, and high incidence \nscenario uses hospitalization rate from July 2022\n2Interval refers to the time between the most recent monovalent dose and a bivalent dose. \nDosing intervals for monovalent booster and bivalent \nbooster, by age group \nIZ Data Lake: Accessed 2/7/20230% 20% 40% 60% 80% 100%\n12-17 year olds\n18-49 year olds\n2-4 month interval 5-7 month interval\n8-10 month interval 11+ month interval0% 20% 40% 60% 80% 100%\n12-17 year olds\n18-49 year olds\n2-4 month interval 5-7 month interval\n8-10 month interval 11+ month intervalInterval between completion of the primary series \nand monovalent boosterInterval between completion of the most recent \nmonovalent dose * and bivalent booster\n* Primary series or monovalent boosterAmong adolescents who received a monovalent booster, nearly half received the \nmonovalent booster at an interval <8 months after their primary series \nOver 90% of adolescents received a bivalent booster ≥8 months after their previous dose\nLimited data to inform myocarditis risk after bivalent COVID- 19 vaccine booster dose \n–\n–\n–Preliminary VSD myocarditis rates following b ivalent booster dose in adolescent and young adult \nmales lower than first monovalent boosters, but limited by small numbers of doses administered\nMyocarditis risk lower wi th longer time between doses \nRates of myocarditis lower with extended interval between dose 1 and dose 2 for primary series1\nLonger interval between doses for bivalent boosters, compared to monovalent boosters, may \nalso impact myocarditis rates\nMost individuals with myocarditis/pericarditis have f ully recovered at follow-up2\nThe risk of adverse cardiac outcomes were 1 .8 –5.6 times higher after SARS -CoV-2 \ninfection than after mRNA COVID-19 vaccination among males ages 12- 17 years3Myocarditis and COVID-19 vaccines\n111 https://www.cdc.gov/vaccines/acip/meetings/downloads/slides -2022-02-04/11-COVID -Moulia-508.pdf2https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2022-02-04/04-COVID -Kracalic-\n508.pdf3https://www.cdc.gov/mmwr/volumes/71/wr/mm7114e1.htm?s_cid=mm7114e1_w\nVSD incidence rates of verified myocarditis or pericarditis in the 0 -7 days \nafter Pfizer-BioNTech vaccination in people 12 –39 years1\n1Primary series and 1stmonovalent booster data through August 20, 2022, bivalent booster data through January 29, 2023; Source: Kristin Goddard, Kay laE. Hanson, Ned Lewis, \net al. Incidence of Myocarditis/Pericarditis Following mRNA COVID -19 Vaccination Among Children and Younger Adults in the United States .Ann Intern Med. [Epub 4 October \n2022]. doi: 10.7326/M22- 2274Dose 2 Primary Series \nPfizer -BioNTech1stMonovalent Booster Dose \nPfizer -BioNTechBivalent Booster Dose\nPfizer -BioNTech\nAge & Sex Cases Dose 2 \nTotalIncidence rate/ million doses (95% CI)Cases 1\nstBooster \nTotalIncidence rate/ million doses (95% CI)Cases Bivalent Booster TotalIncidence rate/ million doses(95% CI)\n12-17 Years\nMalesFemales456308,046311,247146.1 (106.6 – 195.5)\n19.3 (7.1 – 42.0)142129,487139,118108.1 (59.1 –181.4)\n14.4 (1.7 – 51.9)0048,06649,7250.0 (0.0 – 62.3)0.0 (0.0 – 60.2)\n18-29 Years\nMalesFemales272331,889400,32181.4 (53.6 –118.4)\n5.0 (0.6 – 18.0)71166,973240,22641.9 (16.9 – 86.4)\n4.2 (0.1 – 23.2)1050,68780,21119.7 (0.5 – 53.1)\n0.0 (0.0 – 37.3)\n30-39 Years\nMalesFemales53341,527410,71314.6 (4.8 – 34.2)\n7.3 (1.5 – 21.3)31197,554268,41215.2 (3.1 – 44.4)\n3.7 (0.1 – 20.8)0082,191115,0140.0 (0.0 – 36.4)0.0 (0.0 – 26.0)\n12\nVSD incidence rates of verified myocarditis or pericarditis in the 0 –7 days \nafter Moderna vaccination in people ages 18 –39 years1\n1Primary series and 1st monovalent booster data through August 20, 2022, bivalent booster data through January 29, 2023; sourc e: Goddard K, et al. Incidence of Myocarditis/Pericarditis \nFollowing mRNA COVID -19 Vaccination Among Children and Younger Adults in the United States .Ann Intern Med. 2022;175:1169- 1771.Dose 2 primary series \nModerna1stmonovalent booster dose \nModernaBivalent booster dose\nModerna\nAge/sex CasesDose 2\ntotalIncidence rate/\nmillion doses\n(95% CI)Cases1stbooster\ntotalIncidence rate/\nmillion doses\n(95% CI)CasesBivalent\nbooster\ntotalIncidence rate/\nmillion doses\n(95% CI)\n18–29 years\nMalesFemales19\n0195,809\n243,56097.0 (58.4 – 151.5)\n0.0 (0.0 – 12.3)71109,337156,70764.0 (25.7 – 131.9)\n6.4 (0.2 – 35.6)0\n018,49929,5610.0 (0.0 –161.9)\n0.0 (0.0 –101.3)\n30–39 yearsMalesFemales8\n1216,583259,78036.9 (15.9 – 72.8)\n3.9 (0.1 – 21.4)12149,468191,7656.7 (0.2 – 37.3)\n10.4 (1.3 – 37.7)0\n035,31847,6200.0 (0.0 –84.8)\n0.0 (0.0 –62.9)\n31 –136 hospitalizations prevented\n9 –40 ICU admissions prevented\n0 –1 death preventedEstimated COVID -19 hospitalizations prevented vs. potential myocarditis \ncases for every million bivalent mRNA COVID -19 booster doses: \n12 –17-year -olds\nPer million doses in 12 –17-year -olds over 6 months1\n140 myocarditis2cases in 48,066 males with a bivalent booster \n0 myocarditis2cases in 49,725 females with a bivalent booster \n1Ranges presented for benefits are based on the high and low incidence scenarios presented on slides 7 and 8\n2Based on preliminary Pfizer- BioNTech bivalent booster safety data from VSD (incident rate/million doses): 0 (95% CI: 0- 62) in males and 0 (95% CI: 0- 60) in females  \n17–75 hospitalizations prevented\n5 –22 ICU admissions prevented\n0 – 1death preventedEstimated COVID -19 hospitalizations prevented vs. potential myocarditis cases for \nevery million bivalent mRNA COVID -19 booster doses: 12 –17-year -olds \nAccounting for potential incidental SARS-CoV- 2 infections among hospitalized patients1\nPer million doses in 12 –17-year -olds over 6 months2\n150 myocarditis3cases in 48,066 males with a bivalent booster \n0 myocarditis3cases in 49,725 females with a bivalent booster \n1 Results were adjusted to account for potential incidental findings of SARS -CoV- 2 infection by multiplying the estimated hospital izations, ICU admissions, and deaths prevented by the estimated \npercent of COVID -NET hospitalizations that are likely due to COVID- 19 among 12 –17-year -olds during on Omicron BA.5 predominant period (55%)\n2 Ranges presented for benefits are based on the high and low incidence scenarios presented on slides 7 and 8\n3Based on preliminary Pfizer- BioNTech bivalent booster safety data from VSD (incident rate/million doses): 0 (95% CI: 0- 62) in males and 0 (95% CI: 0- 60) in females  \n117 –376 hospitalizations prevented\n21 –69 ICU admissions prevented\n4 –11 deaths preventedEstimated COVID -19 hospitalizations prevented vs. potential myocarditis \ncases for every million bivalent mRNA COVID -19 booster doses: \n18 –49-year -olds\nPer million doses in 18 –49-year -olds over 6 months1\n161 myocarditis2case in 186,695 males with a bivalent booster \n0 myocarditis2cases in 272,406 females with a bivalent booster \n1Ranges presented for benefits are based on the high and low incidence scenarios presented on slide 7\n2Based on preliminary bivalent booster safety data from VSD among persons ages 18 -39 years. Among Pfizer -BioNTech recipients, rates per million doses were: 20 (95% CI: 1– 53) in males \nages 18 –29 years; 0 (95% CI: 0– 37) in females ages 18 –29 years; 0 (95% CI: 0– 36) in males ages 30 –39 years and 0 (95% CI: 0– 26) in females ages 30 –39 years. Among Moderna \nrecipients, rates per million doses were: 0 (95% CI: 0– 162) in males ages 18 –29 years; 0 (95% CI: 0– 101) in females ages 18 –29 years; 0 (95% CI: 0– 85) in males ages 30 –39 years and \n0 (95% CI: 0– 63) in females ages 30 –39 years. \n81 –259 hospitalizations prevented\n15 –48 ICU admissions prevented\n3 –8 deaths preventedEstimated COVID -19 hospitalizations prevented vs. potential myocarditis cases for \nevery million bivalent mRNA COVID -19 booster doses: 18 –49-year -olds\nAccounting for potential incidental SARS-CoV- 2 infections among hospitalized patients1\nPer million doses in 18 –49-year -olds over 6 months2\n171 myocarditis3case in 186,695 males with a bivalent booster \n0 myocarditis3cases in 272,406 females with a bivalent booster \n1 Results were adjusted to account for potential incidental findings of SARS -CoV- 2 infection by multiplying the estimated hospital izations, ICU admissions, and deaths prevented by the \nestimated percent of COVID- NET hospitalizations that are likely due to COVID- 19 among 18 –49-year -olds during on Omicron BA.5 p redominant period (69%)\n2 Ranges presented for benefits are based on the high and low incidence scenarios presented on slides 7 and 8\n3Based on preliminary bivalent booster safety data from VSD among persons ages 18 -39 years. Among Pfizer -BioNTech recipients, rates per million doses were: 20 (95% CI: 1– 53) in males ages \n18–29 years; 0 (95% CI: 0– 37) in females ages 18 –29 years; 0 (95% CI: 0– 36) in males ages 30 –39 years and 0 (95% CI: 0– 26) in females ages 30 –39 years. Among Moderna recipients, rates \nper million doses were: 0 (95% CI: 0– 162) in males ages 18 –29 years; 0 (95% CI: 0– 101) in females ages 18 –29 years; 0 (95% CI: 0– 85) in males ages 30 –39 years and \n0 (95% CI: 0– 63) in females ages 30 –39 years. \n18\n\n\n\n\nBenefits of vaccination may continue to accrue beyond time horizon used\nStable hospitalization rates were assumed for the duration of the time horizon\nUnde\nrlying complexity of vaccine histories and previous infections could not be \naccounted forCOVID -NET hospitalization rates include hospitalizations for which COVID- 19 was not a \nprimary reason for admission\nCurrent COVID -19 epidemiology, including hospitalization rates used in assessment,  \nreflects impact of both prior vaccination and prior infection\n–Cannot account for possible future increases in COVID -19 hospitalization rates or new variant\nMy ocarditis rates following bivalent booster dose are uncertain. Studies are underway \nto assess the long- term impact of vaccine- associated myocarditisLimitations\nBenefits c ontinue to outweigh risks for primary series vaccination in all age groups\nBenefits of bivalent booster dose vary by age, time since last dose, and COVID- 1 9 incidence\nRisk of myocarditis after COVID- 1 9 vaccines likely reduced by longer interval since last dose\n–Additional data can better define risk after bivalent vaccines, but current data encouraging\nChanges in COVID-19 hos pitalization rates would impact the benefit assessment\nAdditional b enefits of COVID-19 vaccines unable to be quantified in benefit- risk assessment\n–Likely prevention of post- COVID conditions, possible reduction in transmission, increased confidence \nin social interactions\nBenefit risk assessment will continue to be monitored as new data are available \nReceipt of primary series c ontinues to be important in all ages \nBoosters r emain an important option to improve protection against severe COVID- 19, \nespecially for higher -risk populations\n19Summary of benefit-risk balance for bivalent mRNA COVID -19 vaccination\nVEaP Team\n–\n–\n–––Da\nni Moulia\nSara OliverEvelyn TwentymanKatherine Fleming -Dutra\nR\nuth Link-Gelles\nC\nOVID -NET\n–Chris Taylor\nISO––Eric WeintraubTom ShimabukuroAcknowledgements\nFor more information, contact CDC\n1-800-CDC- INFO (232- 4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position o f the Centers for Disease Control and Prevention.\nPhotographs and images included in this presentation are licensed solely for CDC/NCIRD online and presentation use. No rights are implied or extended for use in printing or\nany use by other CDC CIOs or any external audiences.\n Thank you", "summary": "Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Centers for Disease Control and Prevention National Center for Immunization and Respiratory Diseases Photographs and images included in this presentation are licensed solely for CDC/NCIRD online…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/COVID-09-Wallace-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 21}
{"title": "COVID 10 Oliver 508", "content": "cdc.gov/coronavirus\nCOVID -19 Vaccine : \nConsiderations for Future Planning\nSara Oliver, MD, MSPH\nACIP MeetingFebruary 24, 202 3\nConsiderations for future planning\nCOVID -19 vaccines\nCOVID -19 vaccines: \nWhere we are now How do we \nget there?COVID -19 vaccines: \nWhere we are going  \nConsiderations for future planning\nCOVID -19 vaccines\nCOVID -19 vaccines: \nWhere we are now How do we \nget there?COVID -19 vaccines: \nWhere we are going  \nConsiderations for future planning\nCOVID -19 vaccines\nCOVID -19 vaccines: \nWhere we are now COVID -19 vaccines: \nWhere we are going  Where we are now :\nCurrent recommendations \nVaccination rates\nHospitalization rates\nHow we get there : \nHow frequently should people get a COVID -19 vaccine? \nAre there groups/populations who should have >1 vaccine per year? Goal : \nSimple\nrecommendations\nCurrent recommendations \nhttps://www.cdc.gov/vaccines/covid -19/images/COVID19- vaccination -schedule -most -people.png\nhttps://www.cdc.gov/vaccines/covid -19/images/COVID19- vaccination -schedule -immunocompromised.png\n\nCoverage / Age (years) <2 2–4 5–11 12–17 18–24 24–49 50–64 >65\nAt least 1- dose† 7.6 10.3 39.7 71.9 81.9 85.2 95.0 95.0\nCompleted primary series 3.7 5.5 32.6 61.6 66.5 72.0 83.7 94.2\n1st monovalent booster* - - 3.3 16.6 27.2 45.3 64.6\n2nd monovalent booster * - - - - - - 10.6 25.3\nBivalent booster** 0.2 0.3 4.0 7.0 6.7 11.2 20.3 40.8\nUnvaccinated 92.4 89.7 60.3 28.1 18.1 14.8 —†—†U.S. COVID-19 Vaccination Coverage (%) of Total Population by \nAge Group — February 8, 2023\n*Monovalent booster dose coverage as of August 26, 2022\n** Bivalent booster coverage is independent of 1stand 2nddose monovalent coverage\n†Note: Coverage is capped at 95%\nSource: https://covid.cdc.gov/covid -data -tracker/#vaccination -demographics -trends Updated February 10, 2023 6\nU.S. COVID-19 vaccine uptake by age group, \nAugust 2021 -January 2023\nSource: IZ Data Lake 01,000,0002,000,0003,000,0004,000,0005,000,0006,000,0007,000,000\nPrimary Series, Ages 12-17 Primary Series, Adults Ages 18-49 Primary Series, Adults Ages 50-64 Primary Series,  Adults Ages 65+\nBooster, Ages 12-17 Booster, Adults Ages 18-49 Booster, Adults Ages 50-64 Booster Adults Ages 65+Primary series authorization \n1stbooster authorization \n2ndbooster authorization Bivalent booster authorization Doses Administered\nCOVID-19 message fatigue challenges vaccine uptake\nRecent studies reflect profound COVID- 1 9 message fatigue1, desire to end use of \nmitigation2, and a common perception among adults that immunity is \nsufficient without further boosters3\nBarriers to vaccine access persist for some populations, i ncluding but not limited to:\n–\n––People living in rural areas\n4\nPeople experiencing homelessness5\nPeople with disabilities6\n•\"If I can't get to it, it doesn't exist for me.\"\nDespite improvements in vaccine equity after primary series vaccination, disparities i\nn booster coverage have emerged7\n1. Guan et al. Health Communication 2022: COVID -19 Message Fatigue: How Does It Predict Preventive Behavioral Intentions and What Types of Information are People Tired of\nHearing About? -PubMed (nih.gov) 2. CDC's State of Vaccine Confidence Insights Reports, Jan 26 2023: CDC’s State of Vaccine Confidence Insights Report 3. Sinclair et al. MMWR Jan \n20 2023: MMWR, Reasons for Receiving or Not Receiving Bivalent COVID -19 Booster Vaccinations Among Adults —United States, November 1 –Dec ember 10, 2022 (cdc.gov)\n4.Assessing barriers to access and equity for COVID -19 vaccination in the US -PMC (nih.gov) 5. McCosker et al. Vaccine May 2022: Strategies to improve vaccination rates in people \nwho are homeless. 6. Griffin -Blake et al. Barriers and facilitators of COVID -19 vaccine uptake among people with disabilities. P resentation to the COVID -19 Vaccine Innovation Team: \nFeb 8 2023. 7. COVID -19 Vaccination Coverage, by Race and Ethnicity —National Immunization Survey Adult COVID Module, United States, December 2020– November 2021 | \nMMWR (cdc.gov)\nPI=Prediction Interval, VOC=Variants of Concern, VBM=Variants Being Monitored . https://covid.cdc.gov/covid -data- tracker/#variant -proportions Accessed Jan 20, 2023Trends in weighted variant proportion estimates & Nowcast\nUnited States, November 6, 2022 –February 11, 2023\nCollection date, week ending\nEstimated Number of Reported COVID -19 Cases by Variant \nVariant Proportions Scaled by Positive Nucleic Acid Amplification Test (NAAT) Counts\nCDC COVID- 19 Lab Coordinating Unit Strain Surveillance and Emerging Variant Group. Data sources: https://covid.cdc.gov/covid- data-tracker/#variant -proportions and \nhttps://covid.cdc.gov/covid- data-tracker/#trends_newtestresultsreported_7daytestingpositive_00\n6M\n04M\n2MPositive tests / Proportion of viral lineages\nSeroprevalenc e by Vaccine and Infection H istory Among \nAdult U.S. Blood Donors, January –June 2022\nQ1 = Jan.–Mar. 2022 \nQ2 = Apr.–Jun. 202243\n35 35\n254438615668 6730\n3733\n433136182417 2020 2225 2818 21 9 108 98 6 7 47 5\n12 106 4\n0%10%20%30%40%50%60%70%80%90%100%\nQ1 Q2 Q1 Q2 Q1 Q2 Q1 Q2 Q1 Q2\nOverall 18 to 49 50 to 64 65 to 74 75 and overSeroprevalence\nAge (years) and quarterNo immunity\nInfection only induced\nimmunity\nBoth vaccine and infectioninduced immunity\nVaccine only inducedimmunity\nSource: https://covid.cdc.gov/covid- data-tracker/#nationwide -blood- donor -seroprevalence- 2022\nWeekly population-based rates of COVID-19 -associated hospitalizations \nby age group— COVID -NET, March 2020 –February 2023\nGray boxes indicate potential reporting delays. Interpretation of trends should be excluded from these weeks. \nAge Group\nMonthly Age-Adjusted Rates of Lab- Confirmed Hospitalizations by Vaccination Status \namong Adults Ages ≥18 Years —COVID- NET, January 2021–December 2022\n0100200300400500600700Rate per 100,000 population\nMonth of Admission\nUnvaccinated Primary series Primary series & ≥1 booster Primary series & ≥2 boosters Vaccinated, no bivalent booster Updated bivalent booster\nData are based on all hospitalizations regardless of reason for admission. Unvaccinated : No recorded doses of COVID -19 vaccine. Primary series ± ≥1 booster: Completed a primary series with or without ≥1 \nbooster dose but did not receive an updated bivalent booster dose. Vaccinated, but no bivalent booster: Completed a primary series with or without ≥1 booster dose but did not receive an updated bivalent \nbooster dose. Updated bivalent booster : Received updated bivalent booster dose. Persons with partial or unknown vaccination status are excluded. See https://covid.cdc.gov/covid-data-tracker/#covidnet -\nhospitalizations-vaccination for complete definitions of vaccination categories. In December 2022, compared to adults who \nreceived an updated bivalent booster dose, \nthe monthly rates of hospitalization were\n-16x higher among unvaccinated and \n-2.6x higher in vaccinated adults without an updated booster dose\nCOVID- 19 vaccine\nWhere we are now\nCurrent COVID- 19 vaccine recommendations are complex\nUptake of current bivalent vaccine is low\nSARS -CoV-2 continues to evolve, but recent virus evolution has not led to large \npopulation- level surges in cases or hospitalizations \nMost adults have a prior infection, prior vaccination, or both\nHospitalization rates are highest older adults , but remain low among people who \nhave received a bivalent booster\nConsiderations for future planning\nCOVID -19 vaccines\nCOVID -19 vaccines: \nWhere we are now COVID -19 vaccines: \nWhere we are going  \nHow we get there : \nHow frequently should people get a COVID -19 vaccine? \nAre there groups/populations who should have >1 vaccine per year? Goal : \nSimple\nrecommendations\nHow frequently should people get a COVID-19 vaccine? \nIncreases in COVID-19 cases (left) and hospitalizations (right) have occurred:\n–During the winter months a nd/or\n–Due to development of new i mmune escape variant\nCases from October 2021- February 2023 highlighted\nhttps://covid.cdc.gov/covid -data-tracker/#trends_weeklycases_select_00 https://covid.cdc.gov/covid -data -tracker/#new -hospital -admissionsAdmissions from October 2021 – February 2023 highlighted\nHow frequently should people get a COVID-19 vaccine? \nWith monovalent COVID- 19 vaccines, \ndeclines in VE noted over time\nLikely impacted by both time since \nvaccine dose and continued virus \nevolution\nAdditional vaccine doses restored \nprotection lost over time\nContinue to monitor impact of waning and virus evolution on VE for bivalent vaccines\nVE = vaccine effectiveness\nBA.2/BA.2.12.1 estimates: Link -Gelles et al. MMWR : https://www.cdc.gov/mmwr/volumes/71/wr/mm7129e1.htm\nBA.4/BA.5 estimates: Link -Gelles et al. medRxiv : https://www.medrxiv.org/content/10.1101/2022.10.04.22280459v1 . Individuals with prior infections excluded. Adjusted for calendar time, \ngeographic region, age, sex, race, ethnicity, local virus circulation, respiratory or non -respiratory underlying medical conditi ons, and propensity to be vaccinated. \n\nHow frequently should people get a COVID-19 vaccine? \nVE = vaccine effectiveness\nCDC unpublished data. Updated from: Tenforde et al. MMWR December 16, 2022: https://www.cdc.gov/mmwr/volumes/71/wr/mm715152e1.htmTime since last dose impacts COVID- 19 vaccine effectiveness\n–Relative VE of bivalent boosters (meaning the additional benefits of a bivalent booster) are higher \nthe longer it has been since the last monovalent dose\nSafety is also likely improved with longer time between doses\n–Myocarditis risk appears lower with longer time between doses \nVISION: VE of bivalent \nCOVID -19 boosters against \nhospitalizations among \nadults aged ≥18 years –\nVISION Network, \nSeptember –December 2022\nHow frequently should people get a COVID-19 vaccine? \nSummary\nWinter months and immune escape variants have impacted COVID- 19 epidemiology\n–This past winter did not see same level of increases in cases/hospitalizations as previous winters \nTime since last COVID- 19 vaccine dose may both increase the incremental benefits of a \nCOVID -19 vaccine, and decrease the risk of myocarditis \nVaccine protection likely declines over time\nA plan for a fall booster dose could provide added protection, at a time when many \nwould be ~1 year from last dose\n–Future epidemiology and SARS- CoV-2 virus evolution could help determine the need for \ncontinued annual boosters\nAre there populations who still need a primary series ? \nUnvaccinated young children\nWhile most adults have completed a primary series, most children ages 6 months –4  years  \nremain unvaccinated\nFor most older children, adolescents, and adults, future doses will be additional ‘boost’ \na\nfter prior infection, prior vaccination, or both\nYoung children will continue to age into the vaccine recommendations at 6 months and c\nould be SARS -CoV-2 naive\nSome population of y oung children likely still need a ‘prime’ and ‘boost’ to optimize \nimmunity\nCoverage / Age (years) <2 years 2–4 years \nAt least 1 -dose 7.6 10.3\nCompleted primary series 3.7 5.5\nUnvaccinated 92.4 89.7\nFor parents with an unvaccinated or under -vaccinated child aged 6 –23 months, 38% \nintend to get their child vaccinated in the next month, whereas 39.4% say they \n‘definitely’ or ‘probably’ will not vaccinate their child and 23% are unsure \nAdditionally, 38% of parents of children ages 2 –4 years say they ‘definitely’ or \n‘probably’ will get their child vaccinated in the next month, while 43.2% say they \n‘definitely’ or ‘probably’ will not and 18.4% are unsure \nDoctor’s offices and clinics were the most trusted place for parents to have their child \nreceive a COVID- 19 vaccine, as reported by 51.1% of parents of children aged 6 –23 \nmonths and 52.5% of parents of children aged 2 –4 yearsParental intent to get a COVID-19 vaccine for their child and \ntrusted places for children to receive a COVID-19 vaccine \nCDC/University of Iowa/RAND survey. Unpublished data. \nGray boxes indicate potential reporting delays. Interpretation of trends should be excluded from these weeks. Are there populations who still need a primary series ? \nUnvaccinated young children\n0510152025Rate per 100,000 population\nWeek Ending Date\n6 months –<2 years 2–4 yearsPediatric hospitalization rates are higher among children 6 months to <2 years of a ge, \ncompared to children 2 –4 years of age\nWeekly Population -Based Rates of COVID-19-Associated Hospitalizations among Children Ages 6 months -4 Years \n—COVID -NET, March 2020– February 2023\n63828993\n0102030405060708090100\nMar-Apr May-Jun Jul-Aug Sep-Oct Nov-DecSeroprevalence (%)\nMonth7585929799\n0102030405060708090100\nMar-Apr May-Jun Jul-Aug Sep-Oct Nov-DecSeroprevalence (%)\nMonthPediatric SARS -CoV- 2 Infection- Induced and Combined (Vaccine -and Infection-\nInduced) Seroprevalence from U.S. Commercial Laboratories —\nMarch –December 2022\nSource: https://covid.cdc.gov/covid- data-tracker/#pediatric -seroprevalence and unpublished data from CDCInfection -induced Combined \n(vaccine- and infection -induced) \n\nAre there populations who still need a primary series ? \nSummary\nChildren ages <2 years have higher COVID- 1 9 \nhospitalization rates than older children\nChildren ages <4 years are less likely to have both \npr\nior infection and prior vaccination\nChildren have frequent visits to healthcare providers\nThe Work Group discussed continued primary series r\necommendations for young children \nBoth ages 6  months- 2 years and ages 6 months-4 \nyears were discussed without a clear consensus\nhttps://www.healthychildren.org/English/family -life/health -management/Pages/Well- Child -Care-A- Check -Up-for-Success.aspx\nShould older adults be recommended for >1 vaccine annually?  \nHospitalization \nr\nates are highest \namong adults 65–74 years and \n≥75 years of age\nAge-Adjusted Rates of COVID -19-Associated Hospitalization by Vaccination Status and \nReceipt of Booster Dose in Adults Ages ≥65 Years \nCOVID -NET, January 2021 –December 2022\nCDC COVID Data Tracker. https://covid.cdc.gov/covid -data -tracker/#covidnet -hospitalizations -vaccination Accessed Feb 17, 2023In December 2022, adults ages ≥65 years \nwho received a bivalent booster had \n12.8X lower risk of hospitalization for \nCOVID- 19 compared to unvaccinated \npeople and 2.5X lower risk of \nhospitalization compared to those \nvaccinated without a bivalent booster\n\nShould older adults be recommended for >1 vaccine annually?  \nImmunity and vaccine\nresponse is different in \nolder adults \nPatterns of vaccine \neffectiveness, including waning, may be different in older adults \nWaning for bivalent VE against hospitalization, including among older adults, isn’t yet known \nUnpublished CDC data. From ACIP presentation February 24, 2022ICATT: Relative VE of bivalent booster against symptomatic infection in \nadults aged ≥ 18 years, December 1, 2022 –February 13, 2023\n\nShould older adults be recommended for >1 vaccine annually?  \nSummary\nOlder adults have higher rates of hospitalization than younger adults\nRates of vaccination among older adults who have received a bivalent COVID- 19 v accine \nbooster dose remain low\nThe Work Group emphasized the importance of older adults being up to date on c urrent \nrecommendations, including receiving a bivalent booster\nThe Work Group discussed more frequent COVID- 19 vaccine doses for older adults, and \nat this time felt the data were insufficient to determine a conclusion\nRecommendations can be updated based on data in older adults including:\n–Hospitalization rates of older adults who have received a bivalent booster\n–Bivalent VE and patterns of waning for older adults \n–SARS - CoV-2 virus evolution and possibility of future immune escape variants\nShould people with immunocompromise be recommended for >1 \nvaccine annually?  \nNumerous studies have demonstrated that mRNA C OVID -19 vaccine effectiveness \namong immunocompromised persons is lower than that of immunocompetent \npersons, including within the period of Omicron predominance\nThis has been demonstrated across a range of immunocompromising conditions, and \ni\ns particularly notable for organ or stem cell transplant recipients\nAmong people with immunocompromise, recommendations prior to the bivalent boos\nter allowed for up to 5 monovalent doses of COVID-19 vaccine\nVaccine effectiveness studies are not yet sufficiently powered to evaluate e\nffectiveness of the bivalent booster among people with immunocompromise\nBritton A, Embi PJ, Levy ME, et al. Effectiveness of COVID -19 mRNA Vaccines Against COVID -19– Associated Hospitalizations Among Immunocompromise d Adults During SARS -CoV-2 Omicron Predominance —VISION Network, 10 States, \nDecember 2021 —August 2022. MMWR Morb Mortal Wkly Rep 2022;71:1335 –1342.\nEmbi PJ, Levy ME, and Patel P, et al. Effectiveness of COVID- 19 Vaccines at Preventing Emergency Department or Urgent Care Encounter s and Hospitalizations Among Immunocompromised Adults: an Observational Study of Real -World Data Across \n10 US States from August—December 2021. Preprint. *Effectiveness of COVID-19 Vaccines at Preventing Emergency Department or Urgent Care Encounters and Hospitalizations Among Immunocompromised Adults: An Observational Study of Real -\nWorld Data Across 10 US States from August- December 2021 (medrxiv.org)\nFerdinands J M, Rao S, Dixon B E, Mitchell P K, DeSilva M B, Irving S Aetal.Waning of vaccine effectiveness against moderate and severe covid -19among adults in the US from the VISION network: test negative, case -control study BMJ 2022; 379 :e072141 doi:10.1136/bmj -2022-\n072141\nShould people with immunocompromise be recommended for >1 \nvaccine annually?  \nVISION: mRNA COVID- 19 VE for \nhospitalizations among immunocompetent \nversus immunocompromised adults \nduring Omicron predominance \n(mid- Dec. 2021—Jul. 2022)\nFigure: Ferdinands J M, Rao S,Dixon B E, Mitchell P K, DeSilva M B, Irving S Aet al. Waning of \nvaccine effectiveness against moderate and severe covid -19 among adults in the US from the \nVISION network: test negative, case- control study BMJ 2022 30\nVE among immunocompromised \nper\nsons is lower than that of \nimmunocompetent persons at comparable time points after dose 2 and dose 3\nVE wanes in both immunocompetent a\nnd immunocompromised persons \nShould people with immunocompromise be recommended for >1 \nvaccine annually?\nSummary\nImmunocompromised adults can have less robust immune response to COVID- 1 9 \nvaccines\nNot currently any authorized prophylactic monoclonal antibody products for populations \na\nt highest risk of COVID- 19 \nThe Work Group discussed more frequent COVID- 19 vaccine doses for people with \nimmunocompromise, and at this time felt the data were insufficient to determine a conclusion\nThe Work Group acknowledged this population may continue to be more vulnerable to s\nevere COVID- 19 and likely needs flexibility with COVID- 19 vaccine recommendations \nConsiderations for future planning\nCOVID -19 vaccines\nCOVID -19 vaccines: \nWhere we are now COVID -19 vaccines: \nWhere we are going  Goal : \nSimple\nrecommendations\nCOVID -19 vaccines continue to be the most effective tool we have to prevent serious \nillness, hospitalization and death from COVID -19  \nGoal of COVID- 19 vaccine program continues to be prevention of severe disease\n–Prevention of post -COVID conditions, increased confidence in social interactions important \nas well\nBenefits of additional COVID- 19 vaccine booster doses vary by age, time since last \ndose , and COVID- 19 incidence\nA simplified, annual recommendation could help reduce vaccine and message fatigue\nA COVID -19 vaccine framework that is similar to a well understood influenza vaccine \nframework could be easy for COVID- 19 vaccine providers to implement, and for the \npublic to understand Considerations for future planning\nCOVID -19 vaccines\nSimple recommendations are easier to communicate, which may improve uptake \n–The Work Group was very supportive of simplified recommendations and planning for future \nCOVID -19 vaccines, which could include updated COVID -19 vaccines \nUncertainties remain for ideal timing and populations for future boosters, especially if new immune escape variants develop\nThe Work Group was supportive of a fall/annual COVID -19 vaccine program, with \nflexibility to adjust based on new data, especially for populations at high risk  \nThe Work Group will continue to review data to inform future deliberations: \n–Vaccine effectiveness of bivalent COVID -19 vaccines over time\n–Safety data of bivalent COVID-19 vaccines \n–Cost effectiveness analyses\n–COVID -19 epidemiology, including hospitalization rates among vaccinated and boosted persons\n–SARS -CoV-2 genomic surveillance and virus evolution \n–Data from vaccine manufacturers Work Group interpretation \nConsiderations for future planning\nMonica Godfrey\nEvelyn Twentyman\nDanielle Moulia\nMegan Wallace \nHannah Rosenblum\nLauren Roper\nKatherine Fleming-Dutra\nRuth Link -Gelles\nAmadea Britton\nSarah Meyer\nJulianne Gee\nSusan Goldstein\nMary Chamberland\nElisha HallValerie Morelli\nJoEllen Wolicki\nHeather Scobie\nSierra Scarbrough\nJefferson Jones\nAron Hall\nBarbara Mahon\nData Analytics and Visualization Task Force\nCoronavirus and other Respiratory Viruses Division\nNational Center for Immunization and Respiratory \nDiseasesAcknowledgments\nQuestion for ACIP\n36Discussions about future COVID -19 vaccine recommendations are pre -decisional and \nintended to inform planning and additional analyses. \nWhat are ACIP's thoughts on a simplified framework for future COVID -19 vaccine \nrecommendations?\n–What does ACIP think about children who may still need a primary series? \n–What does ACIP think about future recommendations for older adults? \n–What does ACIP think about future recommendations for people with \nimmunocompromising conditions ? \nFor more information, contact CDC\n1-800- CDC- INFO (232- 4636)\nTTY:  1 -888- 232- 6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.\nThank you", "summary": "cdc.gov/coronavirus COVID -19 Vaccine :  Considerations for Future Planning Sara Oliver, MD, MSPH ACIP MeetingFebruary 24, 202 3 Considerations for future planning COVID -19 vaccines COVID -19 vaccines:  Where we are now How do we  get there?COVID -19 vaccines:  Where we are going   Considerations for future planning COVID -19 vaccines COVID -19 vaccines:  Where we are now How do we  get there?COVID -19 vaccines:  Where we are going   Considerations for future planning COVID -19 vaccines COVID…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-february-22-24-2023.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2023-02-22-24/COVID-10-Oliver-508.pdf", "doc_date": "2023-02-22", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 37}
{"title": "acip charter", "content": "CHARTER  \n \nADVISORY COMMITTEE ON IMMUNIZATION PRACTICES  \n \n \nAdvisory Committee’s Official Designation.  \n \nAdvisory Committee on Immunization Practices (ACIP or Committee).  \n \nAuthority.  \n \nThe ACIP was established under Section 222 of the Public Health Service Act (42 U.S.C. §2l7a), \nas amended.  The Committee is governed by the provisions of the Federal Advisory Committee \nAct (FACA), Public Law 92-463 (5 U.S.C. § 1001 et seq.), as amended.  \n \nThe ACIP has been given statutory roles under subsections 1928(c)(2)(B)(i) and 1928(e) of the \nSocial Security Act (42 U.S.C. § 1396s(c)(2)(B)(i) and 1396s(e)) and subsection 2713(a)(2) of \nthe Public Health Service Act (42 U.S.C. § 300gg-13(a)(2)).  \n \nObjective and Scope of Activities.  \n \nThe Secretary, Department of Health and Human Services (HHS), and by delegation the \nDirector, Centers for Disease Control and Prevention (CDC), are authorized under Section 311 \nand Section 317 of the Public Health Service Act, [42 U.S.C. §243 and 42 U.S.C. §247b], as \namended, to assist states and their political subdivisions in the prevention and control of \ncommunicable diseases; to advise the state s on matters relating to the preservation and \nimprovement of the public’s health; and to make gr ants to states and, in consultation with t he \nstate health authorities, to agencies and political  subdivisions of states to assist in meeting the \ncosts of communicable disease control programs.  \n \nVaccines have played an important role in public health around the globe.  The Advisory \nCommittee on Immunization Practices (ACIP) prov ides recommendations to the CDC Director \non the use of vaccines and immunization program strategies to inform individuals, clinicians, and \nbroader public health efforts.  This committee convenes scientific and medical experts to provide \nrecommendations based on the best available evidence of vaccine risks and benefits, and \nefficacy.  \nACIP shall provide advice and guidance to the CDC Director regarding use of vaccines and \nrelated agents for effective control of vaccine-preventable diseases and/or decreased \nsymptomatology in the civilian population of the United States and gaps in vaccine safety \nresearch including adverse effects following v accination.  Recommendations made by ACIP are \ninitially reviewed by the CDC Director, and if adopted, become official CDC/HHS \nrecommendations, and may be published in the Morbidity and Mortality Weekly Report \n(MMWR) .  The CDC Director informs the HHS Secretary, and Assistant Secretary for Health, of \nimmunization recommendations provided by the Committee.  Upon the licensure or \nauthorization of any vaccine or any new indicat ion for a vaccine, the Committee shall, as \nappropriate, consider the use of the vaccine at its next regularly scheduled meeting.  If the \nCommittee does not make a recommendation at the Committee’s first regularly scheduled \nmeeting, the Committee shall provide an update on the status of such for the Committee’s \nreview. \n \nDescription of Duties.  \n \nThe Committee shall provide advice for the control of diseases for which a vaccine is licensed or \nauthorized in the U.S.  The guidance will address use of vaccines and may include \nrecommendations for administration of immune globulin preparations and/or antimicrobial \ntherapy shown to be effective in controlling a di sease for which a vaccine is available.  Guidance \nfor use of unlicensed vaccines may be developed if circumstances warrant  and the Committee is \ndirected to develop such guidance by the CD C Director.  For each vaccine, the Committee \nadvises on population groups and/or circumstance s in which a vaccine or related agent is \nrecommended.  The Committee shall also provi de recommendations on contraindications and \nprecautions for use of the vaccine and related agents and provides information on recognized \nadverse events.  The Committee also may provide  recommendations that a ddress the general use \nof vaccines and immune globulin preparations as a class of biologic agents, use of specific \nantibody products for prevention of infectious diseases, and special situations or populations that \nmay warrant modification of the routine recommendations.  \n \nThe main tasks of the Committee can be or ganized into review and recommendations, \nimmunization schedules, and public health strategies.  ACIP shall review the latest scientific \nevidence on vaccine safety, efficacy, and effect iveness to make recommendations on the routine \nuse of vaccines, including for specific populations such as pregnant women, elderly, and \nimmunocompromised individuals. Such review may include evaluation of pre- and post-\nlicensure data or if available, clinical tr ial data for vaccines under an Emergency Use \nAuthorization.  ACIP shall provide recommendations regarding revisions and updates to the \nCDC immunization schedules for children, adoles cents, and adults, taking into account emerging \ndiseases, new vaccines, cumulative exposures to  vaccines and vaccine components, and changes \nin disease epidemiology.  Furthermore, ACIP sh all advise on vaccination strategies that promote \noptimal vaccine coverage, address health di sparities, and ensure equitable access to \nimmunizations across communities.  \n \nCommittee deliberations on use of vaccines to control disease in the U.S. shall include \nconsideration of disease epidemiology and burden of  disease, vaccine risks and benefits, vaccine \nefficacy and effectiveness, the quality of evidence reviewed, economic analyses, and  \nimplementation issues.  The Committee may revise or withdraw their recommendation(s) \nregarding a particular vaccine as new information on disease epidemiology, vaccine \neffectiveness or safety, economic considerat ions, or other data become available.  \n \nKey responsibilities in developing committee r ecommendations can be organized into vaccine \nrecommendations, vaccine safety and monito ring, emerging vaccines and technology, global \nhealth practices, and public engagement and tran sparency as part of ACIP public meetings.  \nACIP shall be responsible for formulating recommendations for routine vaccination schedules \nfor different age groups and high-risk populations, advising on the use of vaccines in emergency \nsituations (such as during disease outbreaks or  public health emergencies), and reviewing \nimmunization practices (incl uding those related to vaccine storage, handling, and \nadministration).  ACIP shall also be responsible for reviewing data on vaccine safety and adverse \nevents, providing recommendations to enhance vacc ine safety surveillance systems, and advising \nCDC on gaps in vaccine safety research; evaluatin g the risk/benefit profiles of vaccines based on \nongoing surveillance and new research findings; cons idering analysis of cumulative effects of \nvaccines and their constituent components; engaging in re-analysis of vaccine safety and efficacy \nas gaps are identified and new information be comes available; and evaluating the risks and \nbenefits of tailoring immunization practices to maximize benefits and reduce risks and take into \naccount variability in immune response for various populations.  Furthermore, ACIP shall be \nresponsible for considering on an ongoing basis th e safety, efficacy, and public health impact of \nnew vaccines, as well as novel vaccine platfo rms such as mRNA vaccines; and evaluating \nvaccines for new diseases or variants of con cern, ensuring that recommendations adapt to new \nscientific evidence and evolving disease landscapes.  ACIP shall also be responsible for \nreviewing global initiatives; and reviewing v accination schedules by other countries and \ninternational organizations.  \n \nACIP shall employ a transparent, evidence-driven decision-making process in developing \nrecommendations.  The Committee shall review cl inical data, listen to expert presentations, and \nconsult with subject matter expert s to determine the benefits and risks of vaccines.  ACIP \ndecisions shall be based on rigorous scientific an alysis and deliberation, with the goal of \nrecommending immunization practi ces that protect and improve public health in the United \nStates.  \n \nIn accordance with Section 1928 of the Social Security Act, ACIP also shall establish and \nperiodically review and, as appropriate, revise the list of vaccines for administration to children \nand adolescents eligible to receive vaccines through the Vaccines for Children Program, along \nwith schedules regarding the appropriate dose and dosing interval, and contraindications to \nadministration of the pediatric vaccines.  The Se cretary, and as delegated by the CDC Director, \nshall use the list established by ACIP for th e purpose of the purchase, delivery, and \nadministration of pediatric vaccines in the Vaccines for Children Program.  \n \nFurther, under provisions of the Affordable Care Act (Section 2713 of the Public Health Service \nAct, as amended), immunization r ecommendations of the Committee that have been adopted by  \nthe Director of the Centers for Disease Control and Prevention must be covered by applicable  \nhealth plans. \n \nAgency or Federal Officer Receiving the Advisory Committee’s Advice/Recommendations . \n \nThe Committee reports to the CDC Director.  Th e CDC Director informs the HHS Secretary and \nthe Assistant Secretary for Health, HHS, of immunization recommendations provided by the \nCommittee.  \n \nSupport.  \n Management and support services shall be provided by the CDC’s: Office of the Chief of Staff; \nNational Center for Immunization and Respirator y Diseases; National Center for Emerging and \nZoonotic Infectious Diseases; and National Center  for HIV/AIDS, Viral Hepatitis, STD, and TB \nPrevention as instructed by the CDC Director, to support ACIP-related activities. \n \nEstimated Annual Operating Costs and Staff Years. \n Estimated annual costs for operating the Commit tee, including (i) Federal personnel (3) and \nother Federal internal costs are $1,080,340; (ii)  proposed compensation and travel expense \npayments for up to 19 members is $42,750; and (iii) reimbursable costs are $83,106. \n \nEstimated Number and Frequency of Meetings.  \n \nMeetings will be held at the discretion of the ACIP DFO in consultation with the Chair. \n \nMeetings shall be open to the public except as determined otherwise by the CDC Director or \nother official, to whom the authority has been delegated, in accordance with the Government in \nthe Sunshine Act (5 U.S.C. § 552b(c)) and Section 10(d) of the FACA (5 U.S.C. § 1009(d)). \nNotice of all meetings shall be given to the public. \n \nDuration. \n \nContinuing. \n \nTermination. \n \nUnless renewed by appropriate action, ACIP will te rminate 2 years from the date this charter is \nfiled. \n \nMembership and Designation. \n The Committee consists of up to 19 voting members, who are Special Government Employees, \nincluding the Chair and Vice Chair.  \n \nMembers shall be selected from authorities who are knowledgeable in the fields of medicine, \nvaccines, immunization practices, immunology, toxicology, pediatric neurodevelopment, \nepidemiology, data science, statistical analysis, heal th economics, recovery from serious vaccine \ninjuries, or public health; have expertise in the use of vaccines or other immunobiologic agents in \nclinical practice or preventive medicine, have expertise with clinical or laboratory vaccine \nresearch, or have expertise in assessment of v accine safety and efficacy.  The Committee shall \ninclude a person(s) knowledgeable about consumer  perspectives and/or social and community \naspects of immunization programs.  Members sh all be deemed Special Government Employees.  \n \nThe Committee also shall consist of non-voting ex-officio members from the Health Resources \nand Services Administration, the U.S. Food and Drug Administration, Centers for Medicare and \nMedicaid Services, National Institutes of He alth, Indian Health Service, and the National \nVaccine Program at HHS or their designees.  \n \nIf fewer than a quorum of ACIP members are eligible to vote due to absence or a financial or \nother conflict of interest, the DFO, or designee, shall have the authority to temporarily designate \nthe ex-officio members as voting members. \n \nThere also shall be 33 non-voting liaison repr esentatives from the American Academy of Family \nPhysicians; American Academy of Pediatrics; American Academy of Physician Associates; \nAmerican College Health Association; American College of Nurse Midwives; American College \nof Physicians; American Geriatrics Society; America’s Health Insurance Plans; American \nImmunization Registry Association; American Medical Association; American Nurses \nAssociation; American Osteopathic Association; American Pharmacists Association; Association \nof Immunization Managers; Association of Americ an Physicians and Surgeons; Association for \nPrevention Teaching and Research; Association of State and Territorial Health Officials; \nBiotechnology Innovation Organization; Council of  State and Territorial Epidemiologists; \nCanadian National Advisory Committee on Immu nization; Infectious Diseases Society of \nAmerica; Independent Medical Alliance;  Interna tional Society of Travel Medicine; Medical \nAcademy of Pediatrics and Special Needs; Nati onal Association of County and City Health \nOfficials; National Association of Pediatric Nurse Practitioners; National Foundation for \nInfectious Diseases; National Medical Assoc iation; Pediatric Infectious Diseases Society; \nPharmaceutical Research and Manufacturers of America; Physicians for Informed Consent; \nSociety for Adolescent Health and Medicine; and Society for Healthcare Epidemiology of \nAmerica.  Liaisons shall be deemed representatives.  \n \nMembers, including the Chair and Vice Chair, sh all be selected by the HHS Secretary and shall \nbe invited to serve for overlapping terms of up to four years, except that any member appointed \nto fill a vacancy for an unexpired term shall be appointed for the remainder of that term.  A \nmember may serve 180 days after the expiration of that member’s term if a successor has not \ntaken office. \n \nSubcommittees. \n \nSubcommittees composed of members of the parent committee and other subject matter experts \nmay be established with the approval of the HH S Secretary.  The subcommittees must report \nback to the parent committee and do not provide advice or work products directly to the agency.  \nThe Department Committee Management Officer will be notified upon establishment of each \nsubcommittee and will be provided infor mation on its name, membership, function, and \nestimated frequency of meetings. \n \nFiling Date.  \n \nApril 1, 2026  \n \nAPPROVED:  \n \n \n \n_________________________  __________________________________ \nDate      Robert F. Kennedy, Jr. \n                   \n March 31, 2026", "summary": "CHARTER     ADVISORY COMMITTEE ON IMMUNIZATION PRACTICES       Advisory Committee’s Official Designation.     Advisory Committee on Immunization Practices (ACIP or Committee).     Authority.     The ACIP was established under Section 222 of the Public Health Service Act (42 U.S.C. §2l7a),  as amended.  The Committee is governed by the provisions of the Federal Advisory Committee  Act (FACA), Public Law 92-463 (5 U.S.C. § 1001 et seq.), as amended.     The ACIP has been given statutory roles…", "source_url": "https://www.cdc.gov/acip/about/acip-charter.html", "pdf_url": "https://www.cdc.gov/acip/downloads/acip-charter.pdf", "case": "acip", "sub_case": "other", "tags": ["acip", "cdc", "vaccines", "other"], "page_count": 6}
{"title": "economics studies guidance", "content": "ACIP Guidance for Health Economics Studies \nGuidance for Health Economics Studies P resented to the Advisory Committee on \nImmunization Practices (ACIP) \nPrepared by \nThe ACIP Ad Hoc WG on Economic Analyses \n(Members listed alphabetically) \nTracy Lieu, M.D., M.P.H. \nProfessor and Director, Center for Child Health  Care Studies Departme nt of Ambulatory Care \nand Prevention \nHarvard Pilgrim Health Care and Harvard Medical School \nACIP Member July 2004-June 2008 \nMartin I. Meltzer, M.S., Ph.D. \nSenior Health Economist & Distinguished Consultant \nCDC/NCPDCID/DEISS \nMark L. Messonnier, M.S., Ph.D. \nLead Economist \nCDC/NCIRD/ISD \n11/13/2007 Page 1 of 9 \n   \n   \n \n \n \n \n \n \n \n \n \n \n \n \n \n ACIP Guidance for Health Economics Studies \nGuidance for Health Economics Studies P resented to the Advisory Committee on \nImmunization Practices (ACIP)  \nRationale for this guidance \nThe Charter of the Advisory Committee on Immuni zation Practices (ACIP) states that, when \nconsidering recommendations for use of a vaccine , ACIP members’ deliberations should include \nconsideration of vaccine efficacy as well as cost:b eneft and risk:benefit anal yses.  In recent years \nthere has been a trend toward an increasing numbe r of economic studies of vaccines presented as \nevidence for the Committee to consider.  Precedent has been established by journals such as the \nBritish Medical Journal  and Vaccine , in that they have adopted standards by which editors and \nreviewers should consider the quality of subm itted economic studies. The Academy of Managed \nCare Pharmacy also has adopted guidelines for economic data submitted in support of formulary \nconsideration. This Guidance has been developed to help ensure the quality of economic data \npresented to the ACIP and its work groups (WG). \nTo ensure the value and consistency of economi c data presented to the ACIP, WG chairs are \nadvised to involve CDC economists from the inception of the WG.  Participation of CDC \neconomists can be facilitated by the National Cent er for Immunization and Respiratory Diseases \n(NCIRD) lead economist, who can coordinate such involvement. \nObjective of this guidance \nIt would be impossible to provide  a set of standards for methods, inputs and values for inputs that \nwould cover all the diverse vaccin e-related issues that the ACIP considers. The objective of this \nguidance is to provide a framework for the desc ription and presentation of methods used to \nexamine the economics of a vaccine-related issue, such that the ACIP readily can understand the \nscience of the analyses.  To ensure that su ch standards have been  achieved, this guidance \nspecifically incorporates technical  review of any economic material s that are to be presented to \nthe ACIP. \nGUIDANCE \nMaterials to be presented \nAll researchers (internal or exte rnal to CDC) wishing to presen t a health economics study (either \nnew or revised/updated) to the ACIP (or one of  its WGs) shall present the following material: \n1) Document or report providing methods and results The document should provide a \ndetailed description of the methods and results.  The level of detail s hould be similar to that \nprovided in a manuscript that would be submitted to a peer-reviewed journal.  However, the \ndocument should not be bound by journal restricti ons on length of the methods and results \nsections. There is no need for a detailed intr oduction section. The discus sion section typically \nwould be shorter than that found in a published manuscript.  Additional details regarding the \ncontent of this document are provided below. \n11/13/2007 Page 2 of 9 \n   \n   \n \n \n  \n \n \n \n \n \n \n \n                ACIP Guidance for Health Economics Studies \n2) Slide sets and other presenta tion materials (e.g., handouts ) The principles and template \nfor slides intended for presentation to the AC IP which outline the methods and results, are \nprovided in the “Guidance: format for presentation of slides” section. Additional details regarding slide content also are provided ( See attached set of “template slides.”) \nTimeline for materials to be made available and review process \nThe report, slides, and ot her presentation material must be submitted to the relevant ACIP WG \nchair and CDC lead staff person no later than 8 weeks before the ACIP general meeting or WG \nmeeting at which the analysis is proposed to be presented. Under  extraordinary circumstance, an \nappeal can be made to the WG chair, the CDC lead staff person, and the NCIRD lead economist \nto submit the report fewer than 8 weeks before th e ACIP meeting. In case of  such an appeal, the \nlead economist will document the justification an d granting of exceptions in collaboration with \nthe WG chair and the CDC lead staff person. \nThe NCIRD lead economist (or designee) will work with the WG chair and CDC lead staff \nperson to identify reviewers for an anonymous peer  review.  Non-CDC revi ewers may be used if \na particular area of e xpertise is not available among CDC ec onomists.  Reviewers will consult \nwith relevant CDC subject-matter experts and return comments a nd questions in writing to the \nNCIRD lead economist (or designee) at least 4 weeks in advance of the formal presentation.  \nThese comments will be forwarded to the WG ch air and CDC lead staff person who will forward \nthem to the appropriate WG members and to th e researchers submitting the economic analysis.  \nThis process will allow time for at least one round  of comments and revisions or responses prior \nto the formal presentation.  Th e relevant WG chair, the CDC lead staff person, and the NCIRD \nlead economist (or designee) will determine if revisions and responses are sufficient to allow \npresentation. If differences persist, the WG chair and the CDC lead staff person, in conjunction \nwith all members of the WG, w ill decide if the information w ill be presented to the ACIP.  \nReviewer comments also will be provided to th e WG and the ACIP to explain the differences \nthat may exist. \n11/13/2007 Page 3 of 9 \n   \n   \n \n \n \n \n \n \n \n \n \n \n  \n \n \n ACIP Guidance for Health Economics Studies \nGUIDANCE: Content of document \nA document describing the methods and results of a health economics study for consideration by \nthe ACIP will contain the follo wing sections and elements: \n1) Affiliations \nAll authors shall incl ude their affiliations. \n2) Statements of conflict or po tential conflicts of interest \nA separate section listing any potenti al conflicts of interest shall be  included for each author.  If \nthere are no potential conflicts of  interest, a statement to that effect must be included (e.g., \nAuthor A: No conflicts of interest). \nMETHODS \n3) Methods: the study question \nThe study question must be explicitly stated in detail (e.g., In this study, we  present results of a \ncost-effectiveness analysis of routinely vacci nating age group XX  against Disease Y, using \nvaccine Z, using three doses given once per year over three consecutive years.) \n4) Methods: the perspective \nThe study must be conducted from the societal perspective unless strong justification is provided \nfor doing otherwise. \nOther perspectives may be in cluded when relevant justif ication is provided for their \nconsideration. The study perspective(s) must be explicitly stated  (e.g., “The perspective used in this study is \nsocietal.”) \n5) Methods: intervention strategies \nIntervention strategies must be clearly identifi ed and completely described.  A baseline strategy \nmust be included. \nAuthors must describe all releva nt interventions.  If the analys is does not include all possible \ninterventions, the authors sha ll provide the rationale for including or excluding them.  For \nexample, the authors of an analysis of vaccinati on of adults against pert ussis would discuss the \nrationale for inclusion or exclusion of a select ive strategy of vaccinati ng care providers of young \ninfants. \n6) Methods: time frame and analytic horizon \nThe time frame and analytic horizon for each stra tegy must be defined clearly, complete with \nappropriate justification (e.g., “W e analyzed benefits and cost s over a ten year period.  The \nanalytic horizon was selected because availabl e data suggest that af ter XX years, vaccine-\n11/13/2007 Page 4 of 9 \n   \n   \n \n \n  \n \n \n \n \n \n ACIP Guidance for Health Economics Studies \ninduced immunity may wane to the point where a large proportion of vaccinees would require a \nbooster dose to maintain adequa te levels of immunity.”). \n7) Methods: the economic model \na) The analytic method used must be specified (e.g., cost-benefit, cost-e ffectiveness, or cost-\nutility analysis).  The summary me asure must be defined/ identified. \nb) The basic model used in the analysis must  be explained in the text without use of \nmathematical notation. Authors may consider en hancing the written desc ription with a word \n“equation”. If deemed necessary by the author s, an equation, or se t of equations, using \nmathematical notation also can be provided in a technical appendix.  \n8) Methods: health outcomes of interest Health outcomes must be clearly identified (e.g., deaths, hospitalizati ons, outpatient visits, \nquality adjusted life years). \nAuthors must ensure that health outcomes are re levant to the perspective.  Although almost any \nhealth outcome may be relevant for a societal  perspective, some health outcomes may be \nirrelevant for any additional perspectives. \n9) Methods: inclusion of epidemiologic models \nWhen an epidemiologic model is an integral part  of a health economics study to be presented to \nthe ACIP, the authors shall include a descripti on of the model.  The authors must include a \nschematic diagram illustrating the model. Annotat ion in such a diagram must be done without \nuse of mathematical notation. Authors are directed to ensure that such schematic diagrams can be \nreadily understood without extensive reading of  the main text (i.e., can “stand alone”). \nThe authors must state the time step used in the epidemiologic model. “Time step” refers to the \ntime associated with the probabi lities used in the model. For example, if the authors use \nprobabilities of death per unit population per year, then the de facto  time step of such a model \nwould be one year. Probabilities, and time step, can be in almost any unit of time. The total \nnumber of time steps must match the time fr ame of the economic model unless a specific \nexplanation is given. \nAuthors should note that it is insufficient mere ly to reference another source (e.g., reference a \npreviously published paper). \n10) Methods: Inputs: values and sources \na) Probabilities: Values and sources must be  presented. Authors mu st make sure that \nprobabilities used in the analysis are “reasonable.”  \nb) Costs: Values and sources must be presen ted. The study shall differe ntiate between direct \nmedical, direct non-medical, indire ct (i.e., productivity), and in tangible costs (included when \nrelevant). The year of cost data also must be st ated.  Authors must make sure that included costs \nare relevant to the stated perspective. \n11/13/2007 Page 5 of 9 \n   \n   \n \n \n \n \n \n \n \n \n \n  \n ACIP Guidance for Health Economics Studies \nc) Other inputs:  Values and sources of any othe r inputs (e.g., Quality Adjusted Life Years) must \nbe presented. \nEach value used in the model must  have at least one clearly identi fied source.  Values that are \nassumed, or calculated (e.g., a resi dual probability), or the results of expert opinion shall be \nidentified as such. Authors are advised that the grea test clarity is often achieved by presenting all input values and \nsources in tabular format.  Such tables must in clude sufficient footnotes to enable a reader to \nreadily understand the table without extensive reading of the main text (i.e., such tables must \n“stand alone”). \n11) Methods: discounting \nAll future costs and benefits shal l be discounted to present value.  This includes future health \noutcomes (e.g., future lives saved must be discounted to present). \nThe discount rate used must be specified, and au thors must ensure that  the discount rate is \nrelevant to the stated perspective. \n12) Methods: sensitivity analyses \nThe general goal of sensitivity an alyses is to demonstrate how conclusions might change with \nchanges in input values. \nSensitivity analyses, including appropriate thresh old analyses, shall be conducted and reported \non cost and incidence variables. The type of sensitivity analysis conduc ted must be described. \nAuthors are strongly encouraged to conduct sensitivity analyses that allow them to identify \nwhich variables within the model are most influential in determining the overall results. The ranges and sources of the values used in the sensitivity analyses must be clearly reported.  \nAuthors shall report values used in sensitivity an alyses in the same table in which they report \nvalues of all inputs (see Point 10). Univariate sensitivity analyses (altering only one value at a time,  and keeping all other values \nfixed at original values ) are unlikely to be considered adequa te. Authors shall present some form \nof multivariate sensitivity analysis or an explan ation as to why such analysis is not presented. \nAuthors must use sensitivity analysis ranges that  are based on clinical ly relevant or policy \nrelevant cutoffs rather than those based on arbitr ary changes in input values (e.g., plus or minus \n10% of initially used values). As a form of sensitivity analysis, in addition to presenting results that have been discounted to \npresent values (see Point 11), undiscounted costs and benefits may be presented. \n13) Methods: independent replication \n11/13/2007 Page 6 of 9 \n   \n   \n \n \n \n \n \n \n  \n \n   \n \n \n \n \n  \n ACIP Guidance for Health Economics Studies \nIn general, information must be presented  that would allow a researcher, with sufficient interest \nand relevant skills, to inde pendently replicate the study.. \nIn order to meet such a standard, where necessa ry, authors may provide additional details in a \ntechnical appendix. \nRESULTS \n14) Results: summary measures \nResults that answer the study question must be identified. Th e summary economic measure(s) \nthat answers the study question must be presented. \nThe summary measure must be appropriat e for the perspective used in the study. \nIf deemed necessary, authors also may wish to present other results calculated during the \nanalysis, such as total number of cases averted. \n15) Results: tables and graphs \nAll tables and graphs used to present result s must be readily understood without extensive \nreading of the main text (i.e., such graphs and tables can “stand alone”). Authors must include \nfootnotes that will help a read er understand each table and graph. \nTables and graphs must add value to the report.  Graphs or tables that c ontain results not central \nto the summary measure (see Point 16) ma y be included in a technical appendix. \nGraphs shall be drawn using the standard guidelines for graphical representation of data. \nDetailed guidelines can be found in texts such as Tufte (Tufte ER. The Visual Display of \nQuantitative Information . Graphics Press, Cheshire Connect icut, 1983: pp. 197).  Examples of \nsuch guidelines include: \n1) Pie charts are almost always unacceptable. \n2) Horizontal and vertical grid lines usually are not needed. \n3) For line charts, typically only 4 lin es (variables) drawn per chart. \n4) For column and bar charts, typically only 4 bars (variables) included per chart. Avoid \nusing “stacked” bars or columns (e.g., a column  that has several elements that add to \n100%). \n5) To allow easy printing and copying, graphs and figures should be drawn in gray-\nscale. Color in graphs and figures should be used sparingly, if at all. \n16) Results: sensitivity anal yses and influential variables \nAuthors shall present their sensit ivity analyses in a clearly id entified section, complete with \nrelevant tables and graphs. \nAuthors shall, whenever possible, present a list of “most influential” variables as identified \nthrough sensitivity analysis (see Point 12). \nDISCUSSION \n11/13/2007 Page 7 of 9 \n   \n   \n \n \n  \n \n \n \n  \n \n \n \n \n \n  \n  ACIP Guidance for Health Economics Studies \n17) Discussion: overall \nThe discussion section should be more limited than that typically found in a peer-reviewed \nmanuscript. \n18) Discussion: limitations \nStudy limitations must be discussed.  Limitations shall include accuracy of any epidemiologic \nmodel and input data (see Points 9 and 10). \nAny implicit assumptions, such as an adequa te supply of vaccine, should be mentioned. \n19) Discussion: relation to other relevant studies \nResults must be discussed in relation to other similar studies if such studies are available. \n20) Discussion: how results may change \nThere must be an explicit discussion, typically  drawing from the results of the sensitivity \nanalyses, of how results would change if ke y assumptions or valu es were to change. \n21) Discussion: no policy implications Unless otherwise requested by the relevant WG ch air, the report must NOT include a discussion \nof the policy implications of the results and limitations.  Because it is CDC’s and ACIP's \nresponsibility to make policy interpretations, such discussion will be deleted if included in the \ndocument distributed for ACIP discussion, unless the WG chair specifically requests it be \nincluded. \n22) Details not addressed in this guidance \nFor further guidance regarding methods a nd results, researchers may follow the \nrecommendations described in the follo wing standard texts (or equivalent): \n1) Prevention Effectiveness: A Guide to D ecision Analysis and Economic Evaluation, 2d . Ed. \nAnne Haddix, Steven Teutsch, and Phaedra Cors o, editors. (New York:  Oxford University \nPress, 2003) \n2) Cost-Effectiveness in Health and Medicine.  Joanna Siegel, Louise Russell, Milton Weinstein, \nand Marthe Gold, editors. (New York: Oxford University Press, 1996). \n23) Additional information \n1) Link to the Community Guide Economic Eval uation abstraction form  where all of the \nimportant components of an EE analysis are pres ented.  The form has a quality rating of EEs at \nthe end. www.thecommunityguide.org/methods/econ-abs-form.pdf \n2) Many standards for conducting economic eval uations are also on the CDC on-line Economic \nEvaluation course. www.cdc.gov/owcd/EET/Preface/Preface.html \n3) The Guide to Community Preventive Servi ces book, chapter 11 is titl ed “Interpreting and \nUsing Economic Evidence”. \n11/13/2007 Page 8 of 9 \n   \n   \n  \n \n \n \n \n \n \n \n  ACIP Guidance for Health Economics Studies \n4) Detsky AS, Laupacis A. Relevance of cost-eff ectiveness analysis to clinicians and policy \nmakers. JAMA. 2007;298:221-4. \nGUIDANCE: format for presentation of slides \nPrinciples for presenting a health economics study to ACIP: \nAfter the document has been peer-reviewed internally, and the WG chair and CDC lead staff \nperson have reviewed and discusse d the contents of the document a nd the relevant analysis, they \nwill decide whether to proceed with invi ting a presentation to the ACIP or WG. \nIt is realistic to assume that many ACIP members will not have had the opportunity to read the document.  Further, the ACIP general meetings (but not WG meetings) are open to the public.  Thus, the presenter of the health economics study should realize that most of the audience at the \npresentation will not be aware of the study, and that the audience members have diverse \nbackgrounds. Further, especially fo r presentations at an ACIP gene ral meeting, it is likely that a \nrelatively short amount of time will be allotte d for the presentation, typically 20-30 minutes \nincluding time for questions. A presentation made in the closed setting of a WG teleconference \nor meeting may be longer and more detailed.   \nTemplate slides: \nThe attached set of template slides provides an outline of the type of slides and suggested layout \nof each type of slide. The subj ect matter of the slides in the template is designed so that a \npresenter can be assured of presenting the main f acts as they relate to the methods, results and \nlimitations of the study. \n11/13/2007 Page 9 of 9", "summary": "ACIP Guidance for Health Economics Studies  Guidance for Health Economics Studies P resented to the Advisory Committee on  Immunization Practices (ACIP)  Prepared by  The ACIP Ad Hoc WG on Economic Analyses  (Members listed alphabetically)  Tracy Lieu, M.D., M.P.H.  Professor and Director, Center for Child Health  Care Studies Departme nt of Ambulatory Care  and Prevention  Harvard Pilgrim Health Care and Harvard Medical School  ACIP Member July 2004-June 2008  Martin I. Meltzer, M.S., Ph.D. …", "source_url": "https://www.cdc.gov/acip/about/health-economics-studies.html", "pdf_url": "https://www.cdc.gov/acip/downloads/economics-studies-guidance.pdf", "case": "acip", "sub_case": "other", "tags": ["acip", "cdc", "vaccines", "other"], "page_count": 9}
{"title": "11 COVID Moulia 508", "content": "cdc.gov/coronavirus\nMyocarditis and COVID- 19 \nVaccine Intervals: \nInternational Data and Policies\nDanielle Moulia, MPH\nACIP MeetingFebruary 4, 2021\nDiscussion background and framework\nGoal: Examine international data and policies on preferential \nrecommendations of an mRNA vaccine product or extended primary series \nintervals as they relate to myocarditis and/or pericarditis* \nDiscussion framework\nInternational data on risk of myocarditis by mRNA vaccine product, focusing on the highest risk group – young males post dose 2\nInternational data on extended primary series interval: risk of myocarditis \nand vaccine effectiveness \nInternational policies and recommendations\n* Myocarditis and/or pericarditis will be referred to generally as “myocarditis,” unless a specific study is being referenced. \nInternational Data on Risk of Myocarditis \nby mRNA Product\nUS:Summary of findings\nVAERS : National, passive surveillance\nAmong males ages 18 –24 years , the myocarditis* reporting rate after a \nsecond dose of Moderna was 40 per million\nVSD: Nine integrated healthcare organizations, active surveillance\nAmong males ages 18 –39 years , the myocarditis/pericarditis** rate after a \nsecond dose of Moderna was 1.5x (aRR‡: 1.5 [0.86–2.61]) than Pfizer\n*As of January 13th, 2022; CDC case definition; 7 -day risk period; **As of January 15th, 2022; CDC case definition, 7 -day risk period\n‡Adjusted for VSD site, age, sex, race/ethnicity, and calendar date\nVAERS: Vaccine Adverse Events Reporting System VSD: Vaccine Safety Datalink\nSource: Su J.  Myopericarditis following mRNA COVID -19 vaccination: Updates from the Vaccine Adverse Event Reporting System (VAERS). Sl ides presented to ACIP WG Dec 17, 2020.\nKlein, N. Myocarditis Analyses in the Vaccine Safety Datalink: Rapid Cycle Analyses and “Head -to-Head” Product Comparisons. Slid es.\nCanada: Summary of findings\nAbraham et al . CAEFISS, passive and enhanced surveillance data\nAmong males ages 18 –29 years the myocarditis/pericarditis* reporting rate \nafter a second dose of Moderna ( 140 per million doses ) was ~5x(aRR‡: 4.73 \n[3.19–7.20]) higher than Pfizer ( 25 per million doses )\nBuchan et al . Ontario, period of enhanced passive surveillance\nAmong males ages 18 –24 years, the myocarditis/pericarditis** reporting rate \nafter a second dose Moderna ( 300 per million doses ) was ~5xhigher than \nPfizer ( 59 per million doses )\n*From December 1, 2020 to October 8,2021;  Myocarditis/pericarditis meeting level 1 -4 of the Brighton Collaboration case definiti on, 7 day risk period ** From December 14, 2020 to \nSeptember 4, 2021, myocarditis/pericarditis meeting level 1 -4 of the Brighton Collaboration case definition, study length risk period; ‡Poisson model conditioned by week \nCAEFISS: Canadian Adverse Events Following Immunization Surveillance System\nSource: https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3988612 .Accessed 1/23/2022\nhttps://www.medrxiv.org/content/10.1101/2021.12.02.21267156v1.article -metrics .Accessed 1/23/2022\nUnited Kingdom: Summary of findings\nYellow Card reporting : Passive and active surveillance of adverse events\nAmong persons ages 18 –29 years , the myocarditis and pericarditis* reporting \nrate after a second dose of Moderna ( 71 per million doses) was ~2.5x higher \nthan Pfizer (24 per million doses)\nPatone et al: Self-controlled case series of myocarditis** hospitalizations in the \nUK\nAmong males ages <40 years, additional events of myocarditis after a second \ndose of Moderna ( 101 per million doses) was >8x than Pfizer (12 per million \ndoses )\n*As of January 19, 2022, reports of suspected myocarditis and pericarditis associated with COVID -19 vaccines ; ** As of November 15, 2021, inpatient admission or death due to \nprimary and secondary ICD -10 of myocarditis, 28 day risk period\nSource: https://www.gov.uk/government/publications/coronavirus -covid -19-vaccine -adverse -reactions/coronavirus -vaccine -summary -of-yellow -card -reporting#yellow- card -reports . \nAccessed 1/22/2022. \nPatone M. 2021 MedRxiv preprint. https://www.medrxiv.org/content/10.1101/2021.12.23.21268276v1.full.pdf . Accessed 1/22/2022.\nNordic Countries : Nordic cohort, myocarditis results\nPresented to VaST on 1/10/2022\nAll residents ages 12 years and older in Denmark, Finland, Norway, and \nSweden (23.1M) from December 2020 –October 2022\nInpatient care for myocarditis and pericarditis\nWithin a 7 -day risk period after either dose, the rate ratio of myocarditis \nfor Moderna vaccine vs. an unvaccinated comparator was higher than \nPfizer vaccine vs. an unvaccinated comparator\n–The highest rate ratios observed were among those receiving a \nsecond dose of Moderna in a heterologous mRNA primary series \nVaST: Vaccine Technical Advisory Workgroup\nSource: Hovi et al., Slides not publicly available.\nDenmark: SARS -CoV-2 vaccination and myocarditis or \nmyopericarditis: population -based cohort study\nDesign: Retrospective cohort\nPeriod: October 2020 –October 2021\nPopulation: 5M persons living in Denmark ages ≥12 years\nOutcome: Hospital diagnosis of myocarditis or pericarditis, increased \ntroponin levels, and a hospital stay lasting >24 hours, 28 -day risk period\nAdjusted using: Cox proportional hazard model with covariates for age, \nsex, vaccine priority group, season, and clinical comorbidities\nSource: Husby et al., SARS -CoV-2 vaccination and myocarditis or myopericarditis: population -based cohort study BMJ 2021; 375 :e068665 doi:10.1136/bmj -2021- 068665\nDenmark: SARS -CoV-2 vaccination and myocarditis or \nmyopericarditis: population -based cohort study\nPopulation Product Absolute Rate per \n100,000 dosesaHR, Unvaccinated \nComparator \n12–39 years Pfizer, after any dose 1.6 (1.0 to 2.6) 1.48 (0.74 to 2.98)\nModerna, after any dose 5.7 (3.3 to 9.3) 5.24 (2.47 to 11.12)\nMales, ≥12 \nyearsPfizer, after any dose 1.5 (1.0 to 2.2) 0.82 (0.50 to 1.34)\nModerna, after any dose 6.3 (3.6 to 10.2) 3.22 (1.75 to 5.93)\nFemales, ≥12 \nyearsPfizer, after any dose 1.3 (0.8 to 1.9) 3.73 (1.82 to 7.65)\nModerna, after any dose 2.0 (0.7 to 4.8) 6.33 (2.11 to 18.96)\nMales, 12 –39 \nyearsPfizer, post dose 2 1.8 (0.8 to 3.4)* 1.54 (0.62 to 3.81)*\nModerna, post dose 2 9.4 (5.0 to 16.0)* 9.80 (4.20 to 22.84) *\n*conducted as part of a post hoc analysis\naHR: Adjusted hazards ratio. Adjusted for age, sex, vaccine priority group, season, and clinical comorbidities.\nSource: Husby et al., SARS -CoV-2 vaccination and myocarditis or myopericarditis: population -based cohort study. BMJ 2021; 375: e068665 doi:10.1136/bmj -2021- 068665.\nFrance and Germany : Summary of findings\nGermany :National, passive surveillance\nAmong males ages 18 –29 years, the myocarditis/pericarditis* \nreporting rate after any dose of Moderna ( 117 per million doses) \nwas >2x higher than Pfizer ( 47 per million doses ) \nFrance :Regional, enhanced passive surveillance \nAmong males ages 18 –24 years, the myocarditis** reporting rate \nafter a second dose of Moderna ( 139 per million doses) was ~3x \nhigher than Pfizer (43 per million doses ) \n*As of September 30, 2021; all reports post mRNA vaccination; **As of September 20, 2021; all reports post mRNA vaccine\nSource: https://www.rki.de/DE/Content/Infekt/EpidBull/Archiv/2021/Ausgaben/46_21.pdf . Accessed 1/23/2022.\nhttps://www.omedit -auvergne -rhone -alpes.ars.sante.fr/index.php/system/files/2021 -10/ANSM_Rapport_CRPV_Moderna_22102021.pdf . Accessed 1/23/2022. \nhttps://ansm.sante.fr/uploads/2021/10/22/20211021- covid -19-vaccins -pfizer -focus -1-2.pdf . Accessed 1/23/2022.\nMyocarditis rate ratios (Moderna vs. Pfizer) country, \nsubgroup, and dose\nKlein, USA, M 18 –39y, post dose 2₽Buchan, Canada -Ontario, M 18 –24y, post dose 2*\nFrance, M 18– 24y, post dose 2*Abraham, Canada , M 18 –29y, post dose 2‡\nHusby , Denmark, M 12 –39y, post dose 2*\nRate Ratio0 5 10 15 20\n*Unadjusted rate ratio; ‡Adjusted with a Poisson model conditioned by calendar week of vaccine administration; ₽ Adjusted for VSD site, age, sex, race/ethnicity, and calendar date\nSource . Husby et al., SARS -CoV-2 vaccination and myocarditis or myopericarditis: population -based cohort study. BMJ 2021; 375: e068665 doi:10.1136/bmj -2021- 068665\nhttps://ansm.sante.fr/uploads/2021/10/22/20211021- covid -19-vaccins -pfizer -focus -1-2.pdf. Accessed 1/23/2022 .\nKlein, N. Myocarditis Analyses in the Vaccine Safety Datalink: Rapid Cycle Analyses and “Head -to-Head” Product Comparisons. Slid es.\nhttps://papers.ssrn.com/sol3/papers.cfm?abstract_id=3988612 .Accessed 1/23/2022\nhttps://www.medrxiv.org/content/10.1101/2021.12.02.21267156v1.article -metrics .Accessed 1/23/2022\nSummary of findings: Myocarditis risk by mRNA product\nRisk of myocarditis may be higher for Moderna than Pfizer vaccine\nLimitations: observational data; rates not readily comparable due to \ndifferences in:\n–Case definition and risk interval length\n–Subpopulations\n–Case ascertainment\n–Calendar time and vaccine implementation factors, including extended primary series intervals\nA limited number of geographic locations are administering both Moderna and Pfizer and had data available.\nInternational Data on Risk of Myocarditis \nwith an Extended Primary Series Interval \nOntario, Canada : Myocarditis/pericarditis by interval\nDesign: Retrospective, population- based cohort, using provincial vaccine registry \nand passive vaccine safety surveillance\nPeriod: December 14, 2020 to September 4, 2021\nPopulation: Adults ages ≥18 years receiving dose 2 on or after June 1, 2021 in \nOntario; 19,740,741 doses of mRNA vaccines\nOutcome: Myocarditis/pericarditis meeting level 1 –3 of the Brighton Collaboration \ncase definition\nAnalysis: Crude reporting rates; overall rate following dose 2 by product estimated \nusing Poisson regression, adjusted for dose 1 product and interval\n–Dosing intervals : ≤30 days (≤4 weeks), 31 –55 days (5– 7 weeks), ≥56 days (≥8 \nweeks)\nSource: Buchan S et al. Dec 2021, MedRxiv preprint.\nOntario, Canada: Reporting rate of myocarditis/pericarditis per million \ndoses among males ages 18 –24 years by vaccine product* and interval\nSource: Buchan S et al. Dec 2021, MedRxiv preprint.\n*Moderna -Pfizer not shown here because there were no reported events in males ages 18 –24 years; a smaller number of males in this age group received this schedule (n=8,853).020040060080010001200140016001800\n≤4 weeks 5-7 weeks ≥8 weeks ≤4 weeks 5-7 weeks ≥8 weeks ≤4 weeks 5-7 weeks ≥8 weeks\nPfizer —Pfizer Moderna —Moderna Pfizer —ModernaRate (95% CI) per million doses\nMales ages 18 -24 y n=235,819 n=93,616 n=85,893\nSummary of data: Myocarditis risk with extended \nprimary series interval\nRates of myocarditis may be lower with extended primary \nseries interval\nReduced rates of myocarditis with extended interval were \nobserved with Moderna and Pfizer vaccines \nSource : Buchan S. Dec 2021, MedRxiv preprint.\nInternational Data on Vaccine Effectiveness \nwith an Extended Primary Series Interval\nBritish Columbia and Quebec, Canada: Vaccine \neffectiveness by primary series interval\nDesign: Test-negative case -control design to estimate vaccine effectiveness\nPeriod: May 30 to October 2, 2021\nPopulation: Community -dwelling adults ages ≥18 years in British Columbia (BC) and \nQuebec, Canada; 1,235,447 specimens, including 44,673 test -positive cases and \n2,460 hospitalizations\nOutcome: Infections and hospitalizations due to SARS -CoV- 2, confirmed by RT -PCR\nAnalysis: Multivariable logistic regression to estimate odds ratios: \n–Adjusted for age group (18 –49, 50– 69, 70– 79, ≥80 years); sex; epi week of the \nanalysis period (weeks 22 –39, categorical); and region of the province\n–Dosing intervals: 3 –4 weeks, 5 –6 weeks, 7 –8 weeks, 9 –11 weeks, 12– 15 weeks, \n16+ weeks\nSource: Skowronski DM. 2021, MedRxiv preprint . \n85 8591 91\n8891 9193979998\n959498\n50556065707580859095100\n0 2 4 6 8British Columbia\nVE against infection VE against hospitalizationBritish Columbia and Quebec, Canada: Vaccine \neffectiveness of any two doses of mRNA vaccines by \nprimary series interval\nSource: Skowronski DM. 2021, MedRxiv preprint . 3–4w    5– 6w     7– 8w    9– 11w    12– 15w  ≥16w ≥7w\nTime between dose 1 and dose 2 (weeks)Adjusted two dose VE (%: 95% CI)\nVE against infection VE against Hospitalization798589 89 89908987979897969597\n50556065707580859095100\n0 1 2 3 4 5 6 7 8Quebec\n3–4w    5– 6w     7– 8w    9– 11w    12– 15w  ≥16w ≥7w\nTime between dose 1 and dose 2 (weeks)\nEngland: Serological responses and vaccine \neffectiveness by primary series interval\nDesign: Test-negative case -control design to estimate vaccine effectiveness\nPeriod: October 2020 to June 2021\nPopulation: Symptomatic adults ages ≥50 years attending community testing (n=308,764 \nunvaccinated persons; n=16,237 persons received Pfizer primary series vaccine); serological \nresponses of 421 immunocompetent adults ages 50 –89 years given two doses of Pfizer at \ndifferent intervals\nOutcome: Testing SARS -CoV -2 positive by PCR through NHS, following COVID -19 compatible \nsymptoms; serological responses 14 –34 days post -dose 2\nAnalysis: Logistic regression to estimate odds ratios by vaccination status\n–Adjusted for a week of onset, age group, gender, region, index of multiple deprivation, ethnicity, \nhealth/social care worker, care home resident, flagged as clinically at extremely increased risk for COVID -\n19 illness, and flagged as extended risk groups among adults ages <65 years \n–Dosing intervals: 3 –4, 5–6, 7–8, 9–12 and > 12weeks\nSource: Amirthalingam G. 2021, Nat Commun.\nPfizer vaccine \neffectiveness against \nsymptomatic SARS -\nCoV-2 infection was \nhigher with an extended interval (>6 \nweeks) compared to a \nstandard interval (3– 4 \nweeks) for all age groups.\nSource: Amirthalingam G. 2021, Nat Commun.\nAge:   ≥80 ≤Jan4  |         ≥80 >Jan 4        |             65 –79             |          50 –64\n100%\n90%\n80%\n70%\n60%\n50%\n40%30%\n20%\n10%0%Post Dose 2 Vaccine Effectiveness (95% CI)\n3-4              9- 12         | 3 -4                 9- 12  >12 | 3- 4        7- 8   9- 12  >12 |  3 -4  5- 6  7- 8  9- 12  >12 \nInterval between Dose 1 and 2 (weeks)England: \nPfizer vaccine \neffectiveness by \nprimary series \ninterval\nSummary: Immunogenicity with extended primary \nseries interval\nPayne et al. (UK ): Among SARS- CoV- 2 infection naïve persons in an observational \ncohort, serological responses were higher after an extended dosing interval (6 –14 \nweek) compared to a standard interval (3 –4 week).\n–Among persons with an extended interval, there were higher antibody and B \ncell responses, as well as sustained B and T cell responses, compared to a \nstandard interval. \n–An extended interval may promote efficient T cell expansion and long -term \nmemory cell persistence.\nAmirthalingam et al. (England), Parry et al. (England), & Grunau et al (Canada): \nNeutralizing antibody titers were higher following an e xtended dosing interval with \nmRNA vaccine, compared to a standard interval.\nSource: Payne R. 2021, Cell.; Amirthalingam G. 2021, Nat Commun.; Parry  H. 2022, Npj Vaccines.; Grunau B. 2022, Clin Inf Dis.\nSummary of data: Vaccine effectiveness with extended \nprimary series interval\nExtended primary series interval may improve immunogenicity and \nvaccine effectiveness.\n–Neutralizing antibody titers were higher following an e xtended dosing interval \n(6–14 week) with mRNA vaccine, compared to a standard interval (3 –4 week). 1-4\n–mRNA vaccine effectiveness against infection and hospitalization was 5 –10% \nhigher with an extended interval (7 –8 weeks vs. 3 –4 weeks). 5\nLimitation: Data collected prior to Omicron surge \n1 Payne R. 2021, Cell.\n2Grunau B. 2022, Clin Infect Dis.\n3 Amirthalingam G. 2021, Nat Commun\n4Parry  H. 2022, Npj Vaccines\n5Skowronski DM. 2021, MedRxiv preprint . \nInternational Policies and \nRecommendations\nCanada\nNACI strongly recommends a complete mRNA COVID- 19 \nvaccine series for persons ages ≥12 years. \n–Ages 12 –29 years: Pfizer is preferred for the primary series.\n–Ages 18 –20 years: Pfizer may be preferred for a booster.\nmRNA vaccine productImmunization \nscheduleMinimum \nintervalAuthorized intervalOptimal interval\nPfizer -BioNTech \nComirnaty2-dose schedule 19 days 21 days 8 weeks\nModerna Spikevax 2-dose schedule 21 days 28 days 8 weeks\nSource: National Advisory Committee on Immunization: Updated Guidance on the use of COVID- 19 Vaccines. (slides)\nhttps://www.canada.ca/en/public -health/services/diseases/coronavirus -disease -covid -19/vaccines/safety- side-effects.html#myocardi tis-and-pericarditis . Accessed 1/23/2022\nhttps://www.canada.ca/en/public -health/services/publications/healthy -living/canadian -immunization -guide -part-4-active -vaccines/p age-26-covid -19-vaccine.html#a5.4 . Accessed 2/1/2022.\nUnited Kingdom\nPreferential recommendation for Pfizer in persons ages 12–17 \nyears\nInterval : at least 8 weeks \n–Ages 16–17 years, at higher risk*: at least 8 weeks\n–Ages 16–17 years, not at high risk: 12 week\n–Ages 12–15 years, higher risk of severe COVID- 19: at least 8 weeks\n–Ages 12–15 years, contact of immunosuppressed person: 8 weeks\n–Ages 12–15 years, not high risk, no contacts: 12 weeks\n*In a recognized clinical risk group (see table 3) and those who work in health and social care should receive two doses of vac cine at an interval of at least eight weeks. This includes those \naged 16 to 17 years who expect to share living accommodation on most days (and therefore for whom continuing close contact is unavoidable) with individuals of any age who are \nimmunosuppressed\nSource: https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/1045852/Greenbook- chapter -14a-11Jan22.pdf .   Accessed 1/22/2022 \nNordic countries\nSweden : Pfizer is recommended for persons ages 12 –30 years over Moderna.\nInterval : 3–4 weeks\nNorway : Pfizer should be offered to persons ages 12 –30 years. Children and \nadolescents ages 5 –15 years may receive 1 or 2 doses based on parents' decision; \npersons ages ≥ 16 years should receive 2 doses\nInterval : 3–12 weeks\n–Persons ages 16 –18 years: 8– 12 weeks\n–Children ages 5 –15 years with severe underlying conditions: 8 –12 weeks, but \ncan be adapted down to 3 weeks based on medical assessment\nSource: https://www.fhi.no/en/id/vaccines/coronavirus -immunisation -programme/coronavirus -vaccine/#vaccination -of-children -and- adolescents . Accessed 1/22/2022 \nhttps://www.lakemedelsverket.se/en/coronavirus/covid -19-vaccine . Accessed 1/23/2022\nhttps://thl.fi/en/web/infectious -diseases- and-vaccinations/what -s-new/coronavirus -covid -19-latest -updates/vaccines -and-coronavir us/getting -vaccinated -against -covid -19-how- why-and- when-\nhttps://www.sst.dk/en/English/Corona -eng/Vaccination -against -covid -19/COVID -19-vaccines -in-Denmark\nNordic Countries\nFinland : Boys and men ages 12 –30 years only offered Pfizer. Girls and \nwomen ages >12 years are offered Pfizer or Moderna. \nInterval : 6–12 weeks for persons ages ≥5 years\nDenmark : Both Pfizer and Moderna vaccines are approved for persons \nages ≥12 years. \nInterval : 3–6 weeks (median interval: 5 weeks)\nSingapore and Taiwan\nSingapore : Children under age 18 years should receive Pfizer vaccine.\nInterval : At least 21 days; guidance notes myocarditis risk may decrease with \na longer interval, but encourages a second dose at 21 days due to Omicron\nTaiwan : Both Pfizer and Moderna vaccines are approved for persons ages \n≥12 years. \nInterval : At least 12 weeks \nSource: https://www.cdc.gov.tw/En/Bulletin/Detail/YPIDZwC4HjqBMtGi4jynHQ?typeid=158 . Accessed 1/31/22\nhttps://www.moh.gov.sg/covid -19/vaccination/faqs ---children -related -vaccination -matters . Accessed 1/31/22\nAustralia\nBoth Pfizer and Moderna vaccines are approved for persons ages 12 \nyears and older. \nInterval : At least 3 weeks (Pfizer) or 4 weeks (Moderna)\n–Children ages 5 –11 years (Pfizer): 8 weeks \n•Can be shortened in special circumstances to a minimum of 3 weeks, such as in an outbreak response, prior to the initiation \nof significant immunosuppression, or international travel\nSource: https://www.health.gov.au/initiatives -and- programs/covid -19-vaccines/advice -for-providers/clinical- guidance/doses -and-administra tion. Accessed 1/30/2022.\nhttps://www.health.gov.au/sites/default/files/documents/2021/12/atagi -recommendations -on-pfizer -covid -19-vaccine -use-in-children -aged -5-to-11-years_0.pdf . Accessed 1/30/2022.\nFrance and Germany\nFrance : HAS recommends persons under the age of 30 years be \ngiven Pfizer over Moderna when available. \nInterval : 6 weeks\nGermany : STIKO recommends persons under the age of 30 \nyears be given Pfizer over Moderna. \nInterval : 3–6 weeks\nHAS: Haute Autorité de Santé; STIKO: Standing Committee on Vaccination\nSource: https://www.nitag -resource.org/sites/default/files/2021 -12/48_21.pdf . Accessed 1/23/2022.\nhttps://www.rki.de/DE/Content/Infekt/EpidBull/Archiv/2021/46/Art_03.html . Accessed 1/23/2022.\nhttps://www.reuters.com/business/healthcare -pharmaceuticals/french -health- authority -advises -against -moderna -covid -19-vaccine -under -30s-2021- 11-09/. Accessed 1/23/2022.\nLimitations\nNot a systematic review; data are biased toward findings that influenced \nnational vaccine policy\nLimited number of countries are administering both Moderna and Pfizer\nCaution should be used when comparing myocarditis/pericarditis rates across studies as surveillance systems, case definitions and risk intervals,  \nsubpopulation age ranges, and vaccine implementation differ substantially\nNational vaccine policies have evolved; some policies extending the primary \nseries interval evolved from implementation strategies to reach the most people with a first dose\nConclusion\nObservational data suggest myocarditis/pericarditis may be associated with \n–Moderna vs. Pfizer in persons ages 18 –29 years, especially males\n–Shorter primary series interval\nSeveral countries have implemented policies or recommendations to \nlengthen the interval between doses (range: 6 -12 weeks) in the primary \nseries and/or preferentially recommend use of Pfizer among males and/or \npersons aged <30 years, which may mitigate the risk of \nmyocarditis/pericarditis and improve vaccine effectiveness\nAcknowledgements\nKatie Curran\nSara Oliver\nMegan Wallace\nMonica Godfrey\nAmy Blain\nAmimah Asif\nSarah Mbaeyi\nEvelyn Twentyman\nTara Jatloui\nSusan Goldstein\nJack Gersten\nJefferson Jones\nEddie Shanley\nAnthony FioreStephen Hadler \nValerie Morelli\nJoEllen Wolicki\nElisha Hall\nErin Ricketts\nFaisal Minhaj\nHeather Scobie\nVTF ACIP WG Team\nACIP COVID -19 Vaccines Work Group\n​​Vaccine Task Force\nEpi Task Force\nData Analytics and Visualization Task Force\nRespiratory Viruses Branch\nFor more information, contact CDC\n1-800- CDC- INFO (232- 4636)\nTTY:  1 -888- 232- 6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.", "summary": "cdc.gov/coronavirus Myocarditis and COVID- 19  Vaccine Intervals:  International Data and Policies Danielle Moulia, MPH ACIP MeetingFebruary 4, 2021 Discussion background and framework Goal: Examine international data and policies on preferential  recommendations of an mRNA vaccine product or extended primary series  intervals as they relate to myocarditis and/or pericarditis*  Discussion framework International data on risk of myocarditis by mRNA vaccine product, focusing on the highest…", "source_url": "https://www.cdc.gov/acip/evidence-to-recommendations/covid-19-2023-2024-monovalent-etr.html", "pdf_url": "https://www.cdc.gov/acip/media/pdfs/2024/09/11-COVID-Moulia-508.pdf", "case": "acip", "sub_case": "other", "tags": ["acip", "cdc", "vaccines", "other"], "page_count": 35}
{"title": "04 COVID Kracalic 508", "content": "cdc.gov/coronavirusMyocarditis Outcomes Following mRNA \nCOVID -19 Vaccination\nPreliminary Data: data are subject to change\nAdvisory Committee on Immunization Practices\nFebruary 4, 2022\nIan Kracalik PhD MPH\nVaccine Safety Team\nCDC COVID-19 Vaccine Task Force\nDisclaimer\nThe findings and conclusions in this report are those of the authors \nand do not necessarily represent the official position of the Centers \nfor Disease Control and Prevention (CDC)\nMention of a product or company name is for identification purposes only does not constitute endorsement by CDC or FDA\n2\nMyocarditis following mRNA COVID -19 vaccination\nEvidence from safety monitoring systems in multiple countries supports the \nfinding of an increased, but still rare, risk of myocarditis following mRNA COVID -\n19 vaccination*\n•Risk:\n‒Highest in adolescents and young adults\n‒Males > females\n‒Following dose 2 > dose 1\n•Onset within a few days of vaccination, mostly within a week\n•Severity of cases varies; most who presented to medical care have responded \nwell to medications and rest\n•Assessment of myocarditis health effects after COVID -19 vaccination in \nprogress 3 * https://www.who.int/news/item/09 -07-2021- gacvs -guidance -myocarditis -pericarditis -covid -19-mrna -vaccines\nCDC enhanced surveillance for myocarditis outcomes after \nmRNA COVID- 19 vaccination in Vaccine Adverse Event \nReporting System (VAERS) case reports* \n4Purpose: Assess functional status and clinical outcomes among individuals \nreported to have developed myocarditis after mRNA COVID -19 vaccination\nMethods: A two -component survey conducted at least 90 days after the onset \nof myocarditis symptoms\n•Patient survey: Focused on 12 –29 years of age, ascertain functional status, clinical \nsymptoms, quality of life, and need for medication or other medical treatment \n•Healthcare provider (e.g., cardiologist): Gather data on cardiac health and \nfunctional status\nTimeline: Data collection August 2021–January 2022\n* https://www.cdc.gov/coronavirus/2019- ncov/vaccines/safety/myo -outcomes.html\nPreliminary data from surveys of patients at least \n90 days post myocarditis diagnosis \n6Outreach focusing on myocarditis patients 12 –29 years of age\nAs of November 2021, VAERS had received ~989 reports of myocarditis or \nmyopericarditis after COVID -19 vaccination that met CDC case definition*\nOf these, ~850 patient ages 12–29 years had reached 90 days post -myocarditis \ndiagnosis\n•Of ~850 patients 90 days post diagnosis, 648 (81%) had a phone number listed\n‒Of the ~648 patients who were called, ~360 (56%) completed the survey; \n~270 (42%) were unreachable and 18 (3%) declined to participate \n‒For the 360 patients interviewed, time from myocarditis onset to interview was 143 days (IQR: 131, 162)\n* https://www.cdc.gov/mmwr/volumes/70/wr/mm7027e2.htm\n020406080100120\nM F M F M F M F\n12 to 14 15 to 19 20 to 24 25 to 29Number of patients\nSex and age group7Most patients diagnosed with myocarditis were young males\nMedian patient age was 18 years (IQR: 15 –22); \nOf the 360 patients 90 days post myocarditis diagnosis, 86% (308) were male\n17%\n2%38%\n6%21%\n3%11%\n2%Male patients\nFemale patients\n8Race and ethnicity of myocarditis patients (N=360) \n0 50 100 150 200 250\nWhite,\n non-Hispanic\nHispanic\nAsian,\n non-Hispanic\nBlack,\n non-Hispanic\nMulti-racial,\n non-Hispanic\nOther,\nnon Hispanic\nAmerican Indian orAlaskan Native,\nnon-HispanicNumber of patients\n62%\n20%\n5%\n4%\n4%\n3%\n<1%\n*4 patients did not provide a response\n987% (314/360) received two doses of a COVID -19 vaccine\n•Of those who received two doses, 98% (307/314) reported receiving                           \nboth doses before they were diagnosed with myocarditis\n•9%(31/360) had a positive COVID -19 test before their                                         \nmyocarditis diagnosisPrior to their myocarditis diagnosis, most patients received \ntwo doses of a COVID- 19 vaccine\n10Self reported previous medical history among patients with \nmyocarditis after mRNA COVID -19 vaccination (N=360)\n60 (17%) had any condition\n•11(3%) had an arrhythmia\n•6(2%) had congenital heart disease\n•6 (2%) had a history of myocarditis\n•2(<1%) had Kawasaki disease \n•1(<1%) had previous heart failure•32 (9%) had a history of asthma\n•7 (2%) had an autoimmune disorder\n•5(1%) genetic or chromosomal condition\n•4 (1%) were immunosuppressed  \n•1 (<1%) had a history of Leukemia\n•1(<1%) had type 1 diabetes \n11Most patients with myocarditis after vaccination reported being \nhospitalized at the time of myocarditis diagnosis (n=360)\n92% (324) were hospitalized\n•4% (13) were readmitted following myocarditis; 8 of 13 (62%) were \nreadmitted because of a concern with the heart\n•20% (71) were prescribed medication for their heart as of their last \nappointment with the provider\n12Missed school or work within the 2 weeks prior to the date of \nthe interview reported among patients with myocarditis after \nvaccination (N=360)\n46 (8%) reported missing school\n•Of these, 10 (37%) believed it was due to their myocarditis\n19(5%) missed work\n•Of these, 7 (37%) believed it was due to their myocarditis\nSelf-reported symptoms within 2 weeks prior to the date of the \ninterview among myocarditis patients (n=360)\n•About half (49%) \nreported \nexperiencing at \nleast 1 symptom in \nthe prior two \nweeks\n0 50 100 150 200 250 300noyesnoyesnoyesnoyesFatigue Palpitations SOB Chest pain\nNumber of patients 1378%\n25%78%\n22%\n75%32%\n68%\n22%Shortness \nof breathChest \npain\nPalpitations\nFatigue\n14EuroQol -5D-5L measurement of health status among patients \nwho developed myocarditis after vaccination (n=242)\n\nPreliminary data from completed cardiologist or \nother healthcare provider surveys\n16Outreach to cardiologists or other healthcare providers\nOf the 360/648 patients interviewed, ~346 (96%) listed contact information for a \ncardiologist or other healthcare provider\n•Of the 346 providers with contact information listed, 229 completed a survey\n•An additional 151 providers completed surveys they had submitted for multiple \npatients in VAERS or provided contact information via the VAERS report\n•We were unable to contact 268 providers\n•In total, 380 providers completed the survey with a median of 191 days (IQR: 170, 216) from patient myocarditis onset to date of provider survey\n17The proportion of myocarditis patients cleared for physical \nactivity by their cardiologist or healthcare provider has increased (n=380) \nAt time of myocarditis diagnosis, 83% of patients \nhad restrictions on their physical activity\n83% \nRestricted\nAt time of provider survey, at least 90 days post \ndiagnosis, only 39% had restrictions\n*25 (7%) were unsure39% \nRestricted\n050100150200250\nSame cardiac status as\nat the initial\nmyocarditis diagnosisImproved, but not\nfully recoveredProbably fully\nrecovered, awaiting\nadditional informationFully recoveredNumber of PatientsBased on the cardiologists/healthcare provider assessment, \nmost patients appear to have fully or probably recovered from their myocarditis (n=380) \n81% (309) of cardiologists or healthcare providers indicated the patient was \nfully or probably recovered\nPatient Recovery66% \n15% 15% \n1% \n*8 providers were unsure 18\nProportion of myocarditis patients deemed to be fully or \nprobably recovered by their healthcare provider (n=309)\n19\nResults of the most recent cardiac function test (n=380)\n53%\n36%93%\n77%\n90%89%46%\n64%\n7%23%\n10% 11%\n050100150200250300350400\nTroponin Cardiac MRI Echocardiogram Electrocardiogram Exercise stress test Ambulatory rhythm\nmonitoringNumber of patientsNormal or baseline Abnormal or elevated\n20\n121\n68\n231832\n28\n1 16383 592\n53\n17\n920\n030 14 3 514\n020406080100120Late gadolinium enhancementInflamation or edemaWall motion abnormalitiesST segment elevationT wave abnormalitiesArrhythmiaConduction delays or blocksEctopic rhythymArrhythmiaOther cardiac concernOther non-cardiac concernArrhythmiaConduction delays or blocksEctopic rhythym\nCardiac MRI Electrocardiogram Exercise stress test Ambulatory rhythym\nmonitoringNumber of patientsAll patientsAbnormal findings from most recent cardiac function test\nPatients fully or probably recovered\nOverlap of abnormal findings among most recent cardiac \nfunction tests\nTroponin 51\nEKG 26 22\nAmbulatory rhythm 3 2 6\nExercise stress test 1 1 1 10\nECHO 9 7 31 20 060–80%\n40–60%\n20–40%\n0–20%\n22\nComparison of cardiac function tests at time of diagnosis and follow -up\n14\n127\n239\n248\n57\n75\n36\n340\n4At �me of ini�al diagnosis At �me of follow -Up\n68\n79\n233\n253\n17\n174110\n20\n186\nNumber of myocardi�s pa�entsNumber of myocardi�s pa�ents\nelevatedelevated\nComparison of cardiac function tests at time of diagnosis and follow -up\n24Number of myocarditis patients Number of myocarditis patients 14\n127\n239At �me of ini�al diagnosis At �me of follow -Up\n68\n79\n233\n\nComparison of cardiac function tests at time of diagnosis and follow -up\n25248\n57\n75      \n253\n17\n110\nAt time of initial diagnosis At time of follow -upNumber of myocarditis patients Number of myocarditis patients \nComparison of cardiac function tests at time of diagnosis and follow -up\n26At time of initial diagnosis At time of follow -up\n36\n340\n4      \n174\n20\n186\nelevatedelevatedNumber of myocarditis patients Number of myocarditis patients \nNormal/Baseline function or absence of symptoms\nAbnormal function or presence of symptoms\nUnknown or no test results available\nPatients deemed fully or probably fully recoveredPatients deemed not recovered\n27Cardiac assessment and symptoms among patients deemed to be \nrecovered and not recovered from their myocarditis\nNormal/Baseline function or absence of symptoms\nAbnormal function or presence of symptoms\nUnknown or no test results availablePatients deemed not recoveredCardiac assessment and symptoms among patients deemed to be \nrecovered and not recovered from their myocarditis\n28Patients deemed fully or probably fully recovered\nNormal/Baseline function or absence of symptoms\nAbnormal function or presence of symptoms\nUnknown or no test results availablePatients deemed not recovered\n29Cardiac assessment and symptoms among patients deemed to be \nrecovered and not recovered from their myocarditis\nPatients deemed fully or probably fully recovered\nSummary\n30At least 90 days after myocarditis diagnosis, most patients reported no impact \non their quality of life, and most did not report missing school or work\nOnly 13 (4%) were readmitted to the hospital \nMost (81%) healthcare providers indicated the patient was probably fully or fully recovered\nThere did not appear to be a single test that was indicative of recovery\nTo our knowledge, there were no vaccine -associated myocarditis deaths in this \ngroup\nOngoing efforts to continue patient follow- up and contact myocarditis patients \nwho were not yet recovered at time of survey \nSurveys are being modified for children aged 5 -11 and follow -up to start in \nFebruary 2022\nAcknowledgments\nVAERS Team\n•VAERS TTS abstraction team\n•VAERS Myopericarditis abstraction team\n•VAERS data team\nClinical Immunization Safety Assessment Project\nCOVID -19 Vaccine Task Force Data Monitoring and Reporting GroupThanks to the many people who made analysis of these data possible:\n31\nFor more information, contact CDC\n1-800- CDC- INFO (232- 4636)\nTTY:  1 -888- 232- 6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.\nThank you!\n32", "summary": "cdc.gov/coronavirusMyocarditis Outcomes Following mRNA  COVID -19 Vaccination Preliminary Data: data are subject to change Advisory Committee on Immunization Practices February 4, 2022 Ian Kracalik PhD MPH Vaccine Safety Team CDC COVID-19 Vaccine Task Force Disclaimer The findings and conclusions in this report are those of the authors  and do not necessarily represent the official position of the Centers  for Disease Control and Prevention (CDC) Mention of a product or company name is for…", "source_url": "https://www.cdc.gov/acip/evidence-to-recommendations/covid-19-2023-2024-monovalent-etr.html", "pdf_url": "https://www.cdc.gov/acip/media/pdfs/2024/09/04-COVID-Kracalic-508.pdf", "case": "acip", "sub_case": "other", "tags": ["acip", "cdc", "vaccines", "other"], "page_count": 32}
{"title": "06 COVID Miller 508", "content": "1\nBooster Doses of Moderna COVID -19 Vaccines in Adults, \nAdolescents & Children\nACIP\nSeptember 1, 2022\nJacqueline Miller, MD\n2Indication for Use of Moderna COVID -19 Vaccine, Bivalent \n(Original And Omicron BA.4/BA.5)\nEUA of Aug 31, 2022\nModerna COVID -19 Vaccine, Bivalent (Original And \nOmicron BA.4/BA.5) is authorized for use in individuals 18 \nyears of age and older as a single booster dose \nadministered at least 2 months after either:\n▪Completion of primary vaccination with any authorized \nor approved monovalent1COVID -19 vaccine, or\n▪Receipt of the most recent booster dose with any \nauthorized or approved monovalent COVID -19 \nvaccine.\n1Monovalent refers to any authorized or approved COVID -19 vaccine that contains or encodes the spike protein of only the Original SARS -CoV-2.\n\n3\nRationale for Variant -Containing Booster Vaccines\n▪Goals of variant -containing booster vaccines1,2\n▪Retain neutralization for Original SARS -CoV-2\n▪Stronger immune response against current variants\n▪Broader cross -neutralization against future variants\n▪Extend durability of protection\n1. FDA Briefing Document for June 26, 2022 VRBPAC Meeting.\n2. WHO Interim Statement on the Composition of Current COVID -19 Vaccines (June 17, 2022).\n4Moderna COVID -19 Investigational Variant -containing \nVaccine Candidates Evaluated In Clinical Trials \n▪Extensive evaluation of 3 monovalent and 4 bivalent investigational variant vaccines in \npast year\n▪>7,000 individuals boosted across all variant vaccine candidates\n▪Bivalent vaccine candidates include :\n25 µg \nOriginal SARS -CoV-2\nBeta -\ncontaining vaccine\n(mRNA -1273.211)\n25 µg \nBeta Variant\n(B.1.351)\nBA.1 Omicron -\ncontaining vaccine \n(mRNA -1273.214)\n25 µg \nOriginal SARS -CoV-2\n25 µg\nOmicron Variant \n(BA.1)\nBA.4/BA.5 Omicron -\ncontaining vaccine \n(mRNA -1273.222)\n25 µg \nOriginal SARS -CoV-2\n25 µg\nOmicron Variant \n(BA.4/BA.5)\n5\nClinical Studies of Booster Doses of Bivalent \nVaccines in Adults  \n6\nClinical Studies with Moderna COVID -19 Investigational \nBivalent Vaccine Candidates in Adults (≥ 18 Years of Age) \n▪All participants previous received a primary series of mRNA -1273 (100 g); participants in Parts G & H \nalso previously received a 3rddose (50 µg) of mRNA -1273\n▪Part G enrolled Mar 8 -23, 2022; Part H enrolled Aug 10 -23, 2022Bivalent Vaccine Study (Part) Dose NMedian \nFollow -up\nBeta \n(mRNA -1273.211)205 (A)3rd (1st \nbooster)300 245 days\nBA.1 Omicron \n(mRNA -1273.214)205 (G)4th (2nd \nbooster)437 43 days\nBA.4/BA.5 Omicron \n(mRNA -1273.222)205 (H)4th (2nd \nbooster) 512 Ongoing\nTotal 1249\nChalkias et al. Research Squa re 2022, doi: 10.21203/rs.3.rs -1555201/v1; in press Nat Med\nChalkias et al. medRxiv 2022, doi: 10.1101/2022.06.24.22276703; in press New Engl J Med\n7Study of 4thDose (2ndBooster) in Adults Using BA.1 Omicron \nBivalent Vaccine (mRNA -1273.214) -\nDemographics and Baseline Characteristics\nStudy 205, Safety Set\nCharacteristic4thDose (2ndBooster)\nOriginal \n(mRNA -1273)\nN = 377BA.1 Omicron \nBivalent \n(mRNA -1273.214)\nN = 437\nMean Age -Years (range) 57.5 (20, 96) 57.3 (20, 88)\n≥ 65 years 39.8% 39.8%\nFemale 50.7% 59.0%\nNon-White Race 14.6% 12.8%\nHispanic / Latino Ethnicity 9.8% 10.5%\nInterval between 2ndand 3rdDose \n(months) –median (range)8.0 (5.6, 14.4) 8.0 (4.7, 15.0)\nInterval between 3rdand 4thDose\n(months) –median (range)4.4 (3.0, 10.2) 4.5 (2.9, 13.4)\nPrior SARS -CoV-2 Infection 26.8% 22.0%\nChalkias et al. medRxiv 2022, doi: 10.1101/2022.06.24.22276703; in press New Engl J Med\n8\nSolicited local adverse reactions within 7 days after injection. No Grade 4 events reported.\n2nddose mRNA -1273 (Baden et al, NEJM 2021); 3rddose mRNA -1273 (Choi et al, Nat Med 2022); 4thdose mRNA -1273.214 ( Chalkias et al. medRxiv 2022; in press New Engl J Med ).Local Reactogenicity of BA.1 Omicron Bivalent (mRNA -1273.214) as 4thDose \nSimilar to 2ndDose of Primary Series and 3rdDose of Original (mRNA -1273) in \nAdults\nStudy 205, Safety Set\n88%84%\n77%\n9%5% 7%12%\n5% 7%14%20%17%\n0%20%40%60%80%100%Pain Erythema\nGrade 1 -2Grade 3Axillary Swelling \nor Tenderness\n4thDose (2ndbooster) using BA.1 Omicron\n(mRNA -1273.214)\nN = 437Swelling\n3rdDose (1stbooster) Original \n(mRNA -1273)\nN = 1672ndDose Original\n(mRNA -1273)\nN = 14,677\n9Systemic Reactogenicity of BA.1 Omicron Bivalent (mRNA -1273.214) as 4th\nDose Generally Lower than 2ndDose of Primary Series and 3rdDose of \nmRNA -1273 in Adults\nStudy 205, Safety Set\n16%\n7%4%59%55%\n44%65%\n59%55%58%\n49%\n40%43% 41%\n31%\n19%\n11% 10%44%\n35%\n24%\n0%20%40%60%80%100%Fever Headache Fatigue Myalgia ArthralgiaNausea /\nVomitingChills\nSolicited systemic adverse reactions within 7 days after injection. a) Grade 4 systemic reactions only with 2nddose of mRNA -1273 (<0.1%).\n2nddose mRNA -1273 (Baden et al, NEJM , 2021); 3rddose mRNA -1273 (Choi et al, Nat Med , 2022); 4thdose mRNA -1273.214 ( Chalkias et al. medRxiv, 2022; in press New Engl J Med ).Grade 1 -2Grade 3a\n4thDose (2ndbooster) using BA.1 \nOmicron bivalent (mRNA -1273.214)\nN = 4373rdDose (1stbooster) Original  \n(mRNA -1273)\nN = 1672ndDose Original\n(mRNA -1273)\nN = 14,677\n10\nSimilar Overall Safety Profile of BA.1 Omicron Bivalent \n(mRNA -1273.214) and Original mRNA -1273 as 4thDose (2ndBooster)\nStudy 205, Safety Set\nUnsolicited AEs within 28 Days After Any Injectionn (%)\nOriginal \n(mRNA -1273)\nN = 377BA.1 Omicron \nBivalent \n(mRNA -1273.214)\nN = 437\nAny AE 78 (20.7%) 81 (18.5%)\nSAE 1 (0.3%) 2 (0.5%)\nFatal AE 0 0\nMedically Attended AE 52 (13.8%) 43 (9.8%)\nAE Leading to Discontinuation from Study 0 0\nSevere AE 3 (0.8%) 4 (0.9%)\n11 Omicron BA.1 Neutralizing Titers Were Significantly Higher Following 4thDose \n(2ndBooster) Using Omicron BA.1 Bivalent (mRNA -1273.214) than with mRNA -1273 \nStudy 205, Per -Protocol Immunogenicity Set with No Prior Infection\n1Based on ANCOVA model adjusting for age group (<65, ≥65 years) and pre -booster titer\n2Common risk difference and 97.5% CI were calculated by Miettinen -Nurminen method adjusted for age group (<65, ≥65 years) \nChalkias et al. medRxiv 2022, doi: 10.1101/2022.06.24.22276703 –in press New Engl J MedSuccess \nCriteria MetParameter                                   4thDose (2ndBooster)\nOriginal \n(mRNA -1273)\nN = 260Omicron BA.1 Bivalent\n(mRNA -1273.214)\n(N = 334)\nGMT Pre -booster \n95% CI332\n(282, 391)298\n(259, 343)\nGMT at Day 291\n95% CI1421\n(1283, 1574)2480\n(2264, 2716)\nGMT Ratio1(Bivalent vs Original)\n97.5% CI1.75 \n(1.49, 2.04)\nSeroresponse rate at Day 29\n95% CI99.2%\n(97.2, 99.9)100%\n(98.9, 100)\nDifference in seroresponse rates2\n97.5% CI1.5 \n(-1.1, 4.0)\nSuperiority ofGMTs: Lower 97.5% CI of GMT Ratio > 1.0\nNon-inferiority ofSeroresponse Rates: Lower 97.5% CI of difference > -10%\n12 Original Strain (D614G) Neutralizing Titers Were Higher Following 4thDose (2ndBooster) \nUsing Omicron BA.1 Bivalent (mRNA -1273.214) than with mRNA -1273 \nStudy 205, Per -Protocol Immunogenicity Set with No Prior Infection\n1 Based on ANCOVA model adjusting for age group (<65, ≥65 years) and pre -booster titer\n2Common risk difference and 97.5% CI (Miettinen -Nurminen) cannot be calculated when SRR in both group is 100%, absolute differen ce is reported.\nChalkias et al. medRxiv 2022, doi: 10.1101/2022.06.24.22276703 –in press New Engl J MedSuccess \nCriteria MetParameter4thDose (2ndBooster)\nOriginal \n(mRNA -1273)\nN = 260Omicron BA.1 Bivalent\n(mRNA -1273.214)\n(N = 334)\nGMT Pre -booster \n95% CI1521 \n(1353, 1710)1267\n(1120, 1432)\nGMT at Day 291\n95% CI5287 \n(4887, 5719)6422\n(5990, 6886)\nGMT Ratio1(Bivalent vs Original)\n97.5% CI1.22 \n(1.08,1.37)\nSeroresponse rate at Day 29\n95% CI100%\n(98.9, 100)100%\n(98.6, 100)\nDifference in seroresponse rates2\n97.5% CI0\nNon-inferiority ofGMTs: Lower 97.5% CI of GMT Ratio >0.67\nNon-inferiority ofSeroresponse Rates: Lower 97.5% CI of difference > -10%\n13\n3.8-fold\nrise\n7.1-fold \nrise\n4.4-fold \nrise\n8.0-fold \nrise\n2.5-fold \nrise\n4.8-fold \nrise\n512\n3321558 1933\n14733886\n432\n29816153070\n23727676\n2002,00020,000\nAll Participants SARS-CoV-2 Negative Pre-Booster SARS-CoV-2 Positive Pre-BoosterOmicron BA.1 Neutralizing Titers After 4thDose (2ndBooster) Significantly \nHigher with BA.1 Omicron Bivalent (mRNA -1273.214) than mRNA -1273 in Adults\nStudy 205, Per -Protocol Immunogenicity Set\nOmicron \nNeutralizing \nAntibody \nID50 GMT\n(95% CI)\nAll Participants\n No Prior Infection\n Prior Infection\nOmicron BA.1 Bivalent\n(mRNA -1273.214)Original \n(mRNA -1273) (N = 367) (N = 428) (N = 260) (N = 334) (N = 98) (N = 94)Pre\nBoostDay \n29Pre\nBoostDay \n29Pre\nBoostDay \n29Pre\nBoostDay \n29Pre\nBoostDay \n29Pre\nBoostDay \n29\nGMR: 1.78\n95% CI: 1.56, 2.04\nGMR: 1.75 \n95% CI: 1.49, 2.04\nGMR: 1.90\n95% CI: 1.50, 2.40\nChalkias et al. medRxiv 2022, doi: 10.1101/2022.06.24.22276703; \nin press New Engl J Med\n14\n18 –< 65 years\n ≥ 65 years\n 18 –< 65 years\n ≥ 65 yearsOmicron BA.1 and Original Strain (D614G) Neutralizing Titers After 4thDose (2nd\nBooster) of BA.1 Omicron Bivalent Were Consistent in Persons ≥65 Years of Age\nStudy 205, Per -Protocol Immunogenicity Set with No Prior Infection\n13041820\n30037344947378\n12351811\n11111522\n28431951987272\n22292590\n1001,00010,000\n18-<65 - Ancestral 65+ - Ancestral 18-<65 - Omicron 65+ - OmicronNeutralizing \nAntibody \nID50 GMT\n(95% CI)\nOriginal SARS -CoV-2\nPre\nBoostDay \n29Pre\nBoostDay \n29\nBA.1 Omicron Bivalent \n(mRNA -1273.214)Original\n(mRNA -1273) (N = 120) (N = 139)Pre\nBoostDay \n29Pre\nBoostDay \n29Pre\nBoostDay \n29Pre\nBoostDay \n29Pre\nBoostDay \n29Pre\nBoostDay \n29\nOmicron BA.1\n(N = 120) (N = 139) (N = 140) (N = 195) (N = 140) (N = 195)\nVRBPAC, June 28, 2022 https://www.fda.gov/media/159492/download \n15\nOmicron B.1 and Original Strain (D614G) Neutralizing Antibodies After 4th\nDose (2ndBooster) Comparable Across Racial Groups\nStudy 205, Per -Protocol Immunogenicity Set with No Prior Infection\n(N=316) (N=376) (N=316) (N=376) (N=26) (N=30) (N=26) (N=30) (N=25) (N=22) (N=25) (N=22)\nPBD29PBD29 PBD29PBD29PBD29PBD29PBD29PBD29PBD29PBD29PBD29PBD29101001,00010,000100,000\n3092333\n207699\n3403352\n3232114\n2942308\n3431520 12346086\n14585639\n12236988\n10354685\n12735894\n15535700Neutralizing Antibody\n(GM Titer, 95%CI)Black/African\nAmericanOther White\nN=234     N=291         N=11        N=24        N=15        N=19       N=234      N=291       N=11        N=24        N=15        N=19\nPrototype (mRNA-1273) Vaccine 50 μg BA.1 Omicron Bivalent Vaccine (mRNA-1273.214) 50 μg Omicron Original SARS-CoV-2\nBlack/African\nAmericanOther White\nPre-booster ( PB), Day 29 post -boost ( D29) \n164thDose (2ndBooster) with BA.1 Omicron Bivalent Booster (mRNA -\n1273.214) Resulted in Higher Neutralizing Antibody Titers against Omicron \nBA.4 & BA.5 than mRNA -1273 in Adults\nPre-booster ( PB), Day 29 post -boost ( D29) \nPBD29PBD29PBD29PBD29 PBD29PBD29101001,00010,000\n7202337\n6091271\n116727\n140492\n173941\n209645Neutralizing Antibody\n(GM Titer, 95%CI)No Prior InfectionPrior Infection All Participants\nN=367        N=428        N=260       N=334           N=98          N=94\nOriginal (mRNA-1273) 50 μg BA.1 Omicron Bivalent Vaccine (mRNA-1273.214) 50 μg\n174th Dose (2ndBooster) with BA.1 Omicron Bivalent Booster (mRNA -1273.214) \nResulted in Higher Neutralizing Antibody Titers against Omicron BA.4/BA.5 \nAcross Age Groups, Including ≥65 Year Olds, than mRNA -1273  \nPre-booster ( PB), Day 29 post -boost ( D29) \nPBD29PBD29PBD29PBD29PBD29PBD29PBD29PBD29PBD29PBD29PBD29PBD29101001,00010,000\n8442783\n5321375\n6582118\n6311245\n132817\n161588\n105670\n123422\n1901039\n192679\n162879\n222624Neutralizing Antibody\n(GM Titer, 95%CI)No Prior Infection Prior Infection All Participants\nOriginal (mRNA-1273) 50 μg BA.1 Omicron Bivalent Vaccine (mRNA-1273.214) 50 μgN=221       N=255      N=146       N=173       N=140      N=195       N= 120     N= 139       N=78        N=60         N=20         N=3418-64 yrs ≥65 yrs 18-64 yrs ≥65 yrs 18-64 yrs ≥65 yrs\n18\nGMR –ratio of GMT of BA.1 Omicron bivalent/GMT of mRNA -1273 at day 29\nVOC –Variant of Concern\nMeso Scale Discovery (MSD) Assay. Nominal alpha = 0.05.\nmRNA -1273 N = 350 -351; mRNA -1273.214 N = 398 -402Binding Antibody Titers Against VOCs Are Significantly Higher after 4thDose \n(2ndBooster) with BA.1 Omicron Bivalent (mRNA -1273.214) than mRNA -1273 in \nAdults\nStudy 205, Per -Protocol Immunogenicity Set\n569\n353502\n384652\n403546\n442\n1001,000\nAlpha Beta Delta GammaBinding \nAntibody \nTiter GMT \n(AU/mL) at \nDay 29\n(95% CI)\nGMR: 1.17\n95% CI: 1.09, 1.24\nAlpha\nGMR: 1.14\n95% CI: 1.07, 1.22\nBeta\nGMR: 1.10\n95% CI: 1.03, 1.16\nDelta\nGMR: 1.16\n95% CI: 1.09, 1.24\nGamma\n500\nBA.1 Omicron Bivalent \n(mRNA -1273.214)Original \n(mRNA -1273) Thousands\n19\n19\nBivalent Beta Vaccine (mRNA -1273.211) as 3rd Dose Elicited Higher \nNeutralizing Antibody Responses in Adults through 6 Months Compared to \nmRNA -1273\nStudy 205 Part A & Study 201 Part B, Per -Protocol Immunogenicity Set, No Prior Infection \nGeometric Mean Ratio –GMT of bivalent beta vaccine (mRNA.1273.211)/GMT of original mRNA -1273 vaccine ofvramRNA -\n1273 N = 149; Bivalent Beta vaccine (mRNA -1273.211) N = 295\nChalkias et al. Research Square 2022, doi: 10.21203/rs.3.rs -1555201/v1 –in press Nature Medicine\n20\nPre-Clinical Studies of Booster Doses of Bivalent \nBA.4/5 -Containing Vaccine (mRNA -1273.222) in \nMice\n21\nIncreased Immunogenicity after Booster Dose of the BA.1 & BA.4/BA.5 \nOmicron Bivalent Vaccines (mRNA -1273.214 & mRNA -1273.222) in Mice\nBA.1, pre and post boost comparison•K18 hACE2 mice previously vaccinated with primary series of mRNA -1273 (n = 8 -10 per group)\n•Boosted with Original (mRNA -1273),  BA.1 Omicron Bivalent (mRNA -1273.214), or BA.4/BA.5 Bivalent (mRNA -\n1273.222\n•~31 weeks between primary series & booster\n•Low 0.25 µg dose used to allow for differences between dose regimens to be captured\nNeutralization (before and 4 weeks after booster)\nScheaffer et al, manuscript under preparationBA.1 neuts: \n•7-and 3 -fold increase from bivalent \nvaccines\nBA.5 neuts:  \n•4.2-and 4.5 -fold increase from \nbivalent vaccines\nLimited boost from mRNA -1273 ns –not significant\n*   p <0.05\n**  p <0.01\nPBS = 1273 primary series + PBS boosterBA.5, pre and post boost comparison\n22\nIncreased Protection from BA.5 Challenge after Booster Dose of BA.4/BA.5 \n& BA.1 Omicron Vaccines (mRNA -1273.214 & mRNA -1273.222) in Mice\nScheaffer et al, manuscript under preparationBivalent vaccines \nbetter protect from \nBA.5 infection in lungs\nns –not significant\n*       p <0.05\n**      p <0.01\n***    p <0.001\n****   p <0.0001\nControl = PBS primary series & booster\nPBS = 1273 primary series + PBS booster•Mice challenged with 104PFU of BA.5 virus 4 weeks after booster dose\n\n23\nOngoing Studies of Booster Doses in Adolescents \nand Children, 6 Months -17 Years of Age\n24\n24Studies of Booster Dose of Original (mRNA -1273) Vaccine \ninAdolescents & Children, 6 -17 Years \nStudies 203 & 204\n•3rddose (1stbooster) administered after completion of primary series\nStudy AgeBooster\nDoseMonths between \n2ndDose & \nBooster (range) N\n203 12-17 years 50 g 10.4 (9.0, 13.9) 1346\n204 6-11 years 25 g 7.4 (4.1, 12.4) 1294\n•Submission of data to the FDA is ongoing\n25\n25Ongoing Study of BA.1 Omicron Bivalent Vaccine (mRNA -1273.214) \nPrimary Series & Booster Dose in Infants & Children, 6 Months -5 Years \nStudy 306\n•Open -label, Phase 3 study to evaluate safety & immunogenicity\nPart History Vaccine Series Vaccine\nDose N Status\n1 Vaccine \nnaive2-dose \nprimary series25 g 480\n(320 2 -5 years; \n160 6 -23 months)Enrollment ongoing\n2 Previously \nreceived \nprimary \nseries1 booster dose 10 g 480 \n(320 2 -5 years; \n160 6 -23 months) 2-5 year olds fully \nenrolled\nEnrollment ongoing \nfor 6-23 month olds\n26\nSummary of Moderna COVID -19 Vaccine Booster Program\nImmunogenicity\nSafety ▪Vaccine boosters generally well tolerated in adults ≥18 years\n▪Local and systemic reactogenicity of BA.1 Omicron bivalent as 4th dose similar to or lower \nthan 2nd dose of primary series & 3rd dose of original vaccine (mRNA -1273) in adults\n▪No new safety concerns identified\n▪Pre-specified immunogenicity objectives met for booster doses in adults\n▪BA.1 Omicron bivalent in adults demonstrated:\n▪Superior responses against BA.1 Omicron compared to Original mRNA -1273 booster in subjects \nwho were antibody negative pre -booster\n▪Significantly higher neutralizing GMT against both BA.4/BA.5 Omicron & Original (D614G) in\nsubjects who were anti -N negative pre -booster\n▪Significantly higher binding titers against Alpha, Beta, Delta and Gamma, confirming a broad \nimmune response regardless of VOC\n▪Consistent immunogenicity across all ages (including ≥65 year olds)\n▪Beta-containing bivalent in adults demonstrated improved durability of neutralizing \nantibodies against VOC through 6 months compared to the original vaccine\n▪Studies of BA.4/BA.5 Omicron bivalent booster in adults & BA.1 Omicron bivalent booster \nin children 6 months -5 years ongoing\n27\nTHANK YOU to Our Study Collaborators, \nInvestigators, and Participants\n•All investigators \n•Study site personnel\n•Most importantly, the individuals who participated in these trials and \ntheir families", "summary": "1 Booster Doses of Moderna COVID -19 Vaccines in Adults,  Adolescents & Children ACIP September 1, 2022 Jacqueline Miller, MD 2Indication for Use of Moderna COVID -19 Vaccine, Bivalent  (Original And Omicron BA.4/BA.5) EUA of Aug 31, 2022 Moderna COVID -19 Vaccine, Bivalent (Original And  Omicron BA.4/BA.5) is authorized for use in individuals 18  years of age and older as a single booster dose  administered at least 2 months after either: ▪Completion of primary vaccination with any…", "source_url": "https://www.cdc.gov/acip/evidence-to-recommendations/covid-19-bivalent-booster-etr.html", "pdf_url": "https://www.cdc.gov/acip/media/pdfs/2024/09/06-COVID-Miller-508.pdf", "case": "acip", "sub_case": "other", "tags": ["acip", "cdc", "vaccines", "other"], "page_count": 27}
{"title": "03 COVID Klein Shimabukuro 508", "content": "cdc.gov/coronavirusSafety update of 1stbooster mRNA      \nCOVID -19 vaccination\nAdvisory Committee on Immunization Practices \n(ACIP)\nApril 20, 2022\nNicola Klein, MD, PhD\nKaiser Permanente Vaccine Study Center\nKaiser Permanente Northern CaliforniaTom Shimabukuro, MD, MPH, MBA\nVaccine Safety TeamCDC COVID- 19 Vaccine Task Force\nSafety Surveillance of 1stBooster Doses in the Vaccine \nSafety Datalink\nNicola Klein, MD, PhD\nKaiser Permanente Vaccine Study Center\nKaiser Permanente Northern California\n\nVaccine Safety Datalink (VSD)\n•Established in 1990\n•Collaborative project between CDC and 9 integrated healthcare organizations\n•Includes ~ 12 million individuals across all sites\n3\nVSD 1stBoosters by Primary Series Vaccination\nData Through April 9th, 2022\n4\n\nVSD 1stBooster Dose by Demographics\n5\n\nVSD Rapid Cycle Analysis (RCA) for Boosters\n•Pre-specified surveillance outcomes were assessed during weekly \nsequential monitoring after 1stCOVID- 19 booster vaccination*\n‒Analyses assess the risk of pre- specified outcomes within 1– 21 days following a booster \nvaccination compared with boosted individuals who are within 22– 42 days following the \nbooster dose, adjusting for age, sex, race/ethnicity, VSD site, time since primary series, \nand calendar time.\n‒Weekly sequential analyses will continue through 2022, with a one- sided p- value \nthreshold for signaling of 0.01.\n‒Due to the association of myocarditis/pericarditis with primary mRNA vaccination, myocarditis/pericarditis cases after the 1\nstbooster were also chart reviewed and \nadjudicated using the CDC case definitions.\n6*Rapid Cycle Analysis (RCA) to monitor the safety of COVID -19 vaccines in near real- time within the Vaccine Safety Datalink. \nAvailable at https://www.cdc.gov/vaccinesafety/pdf/COVID19 -RCA-Protocol -1342- 508.pdf\nVaccinee with Outcome in the Risk Interval and a Concurrent Comparator\n“Boosted Individuals Only”\nOn each calendar day that an outcome occurred \nin a vaccinee (e.g., June 3), w e compared \nvaccinees in their risk interval (day 1– 21) with \nsimilar vaccinees in their comparison interval (day 22–42)\nBy similar, we mean they were in the same age group and of the same sex, race, and at the same VSD site\nComparison Interval 22–42 days post- vaccination 42 22 June 3\nVaccinated with Booster \nMay 31\nRisk Interval 1–21 days post- vaccination21June 3\nVaccinated with \nBooster May 30\n7\nSignals for Pre- specified Outcomes in 21- day Risk Interval Through 4/12/22\nPrimary series with Pfizer -Pfizer OR \nModerna -ModernaPfizer -\nPfizerModerna -\nModernaJanssen\nSignal after 1stBooster Pfizer OR Moderna Pfizer Moderna Pfizer Moderna Janssen\nOutcome Event Signal?\nAcute myocardial infarction No No No No No No\nAppendicitis No No No No No No\nBell's palsy No No No No No No\nCerebral venous sinus thrombosis No No No - - No\nDisseminated intravascular coagulation No No No No - No\nEncephalitis / myelitis / encephalomyelitis No No No - - -\nGuillain -Barre syndrome No No No No - No\nStroke, hemorrhagic No No No No No No\nStroke, ischemic No No No No No No\nImmune thrombocytopenia No No No No No -\nMyocarditis / pericarditis Yes No No No No No\nSeizures No No No No No No\nTransverse myelitis No No No - - -\nThrombotic thrombocytopenic purpura No No No - - No\nThrombosis with thrombocytopenia syndrome No No No - No -\nVenous thromboembolism No No No No No No\nPulmonary embolism No No No No No No\n8 “-” indicates that analyses are not yet possible. \nVSD COVID- 19 RCA\n1stBooster Dose \nMyocarditis and Pericarditis –\nPreliminary Chart Review Analysis\n9\nMyocarditis and Pericarditis: Electronic \nCase Identification using ICD-10 Codes1\nCode List (based on consultation with cardiologist)\n•B33.22 Viral myocarditis\n•B33.23 Viral pericarditis\n•I30.* Acute pericarditis\n•I40.* Acute myocarditis\n•I51.4 Myocarditis, unspecified\n•I31.9 Disease of the pericardium, unspecified\n101Casedefinition excludes individuals with COVID -19 infection <30 days before \nmyocarditis/pericarditis diagnosis. \n* Includes all subcodes.\nChart Review Summary: Myocarditis and Pericarditis \nafter a 1stmRNA COVID-19 Booster Vaccine\n•All electronically- identified cases among all ages up to 98 days post \nvaccination are being chart -reviewed.\n•Chart review is completed for 271 cases through March (25 potential \ncases pending).  \n•Adjudicators verified 139/271 (51%) myocarditis/pericarditis cases.\n•12–39 years old: 53/68 (78%)\n•40+ years old: 86/203 (42%)\n11\nChart Review Summary: Verified Myocarditis and \nPericarditis cases after a 1stBooster Vaccine\n1212–39 year olds 40+ year olds\nCase verification (anytime after vaccination) 53/68 (78%) 86/203 (42%)\nMale sex 38/53 (72%) 51/86 (59%)\nHistory of COVID (>30 days prior to diagnosis) 10/53 (19%) 11/86 (13%)\nHistory of myocarditis/pericarditis 2/53 (4%) 4/86 (5%)\nMedian age 25 years 68.5 years\nMedian time from vaccination to symptom onset 4 days 29.5 days\nAdjudication diagnosis\nMyocarditis 12/53 (23%) 12/86 (14%)\nPericarditis 12/53 (23%) 57/86 (66%)\nMyopericarditis 29/53 (55%) 17/86 (20%)\nTiming of Symptom Onset after 1stBooster: 53 Verified \nMyocarditis and Pericarditis Cases in 12– 39-Year -Olds\n13\n\nTiming of Symptom Onset after 1stBooster: 86 Verified \nMyocarditis and Pericarditis Cases in 40+ year -olds\n14\n\n1Comparison interval is 22– 42 days after booster dose.\n2Adjusted for VSD site, 5- year age group, sex, race/ethnicity, calendar date, and time since primary series.\n3“Either” includes heterologous and homologous primary -> booster doses. Product specific analyses include only homologous primar y->booster doses. \n4Two additional cases were in the risk interval but were not included because there were no appropriate comparators. These cas es are included in the events/million dose calculation.Analysis\nAges VaccineEvents \ninRisk\nIntervalEvents in \nComparison \nInterval1Adjusted \nRate Ratio295%\nConfidence\nInterval2-Sided\nP-valueEvents/Million \nDoses\n1st\nBooster312–39 Either 28 10 4.89 2.24 –11.31 <0.001 20.3 (13.5 –29.3)\n12–39 Pfizer 18 6 5.14 1.86 –15.90 0.001 21.4 (12.7 –33.8)\n12–39 Moderna45 3 3.64 0.79 –19.45 0.097 17.0 (6.8 –35.0)Verified Myocarditis and Pericarditis in the 0–7 Day Risk Interval\nCompared with Events on the Same Calendar Days Among Primary Series and Boosted Comparators\n15\n1Comparison interval is 22– 42 days after booster dose.\n2Adjusted for VSD site, 5- year age group, sex, race/ethnicity, calendar date, and time since primary series.\n3“Either” includes heterologous and homologous primary -> booster doses. Product specific analyses include only homologous primar y-> booster doses. \n4Two additional cases were in the risk interval but were not included because there were no appropriate comparators. These cas es are included in the events/million dose calculation.\n5One additional case was in the risk interval but not included because there were no appropriate comparators. This case is inc luded in the events/million dose calculation.Analysis\nAges VaccineEvents in Risk\nIntervalEvents in \nComparison \nInterval1Adjusted \nRate Ratio295%\nConfidence\nInterval2-Sided\nP-valueEvents/Million \nDoses\nPrimary, \nDose 212–39 Either 112 14 24.38 14.00 –44.96 <0.001 38.2 (31.5 –45.9)\n12–39 Pfizer 83 10 28.07 14.63 –58.50 <0.001 41.4 (33.1 –51.1)\n12–39 Moderna 28 3 24.49 7.82 –105.14 <0.001 30.8 (20.5 –44.5)\n1st\nBooster312–39 Either 28 10 4.89 2.24 –11.31 <0.001 20.3 (13.5 –29.3)\n12–39 Pfizer 18 6 5.14 1.86 –15.90 0.001 21.4 (12.7 –33.8)\n12–39 Moderna45 3 3.64 0.79 –19.45 0.097 17.0 (6.8 –35.0)Verified Myocarditis and Pericarditis in the 0–7 Day Risk Interval\nCompared with Events on the Same Calendar Days Among Primary Series and Boosted Comparators\n16\n1Comparison interval is 22– 42 days after booster dose.\n2Adjusted for VSD site, 5- year age group, sex, race/ethnicity, calendar date, and time since primary series.\n3“Either” includes heterologous and homologous primary -> booster doses. Product specific analyses include only homologous primar y->booster doses. \n4Two additional cases were in the risk interval but were not included because there were no appropriate comparators. These cas es are included in the events/million dose calculation.\n5One additional case was in the risk interval but not included because there were no appropriate comparators. This case is inc luded in the events/million dose calculation.Analysis\nAges VaccineEvents \ninRisk\nIntervalEvents in \nComparison \nInterval1Adjusted \nRate Ratio295%\nConfidence\nInterval2-Sided\nP-valueEvents/Million \nDoses\n1st\nBooster312–39 Either 28 10 4.89 2.24 –11.31 <0.001 20.3 (13.5 –29.3)\n12–39 Pfizer 18 6 5.14 1.86 –15.90 0.001 21.4 (12.7 –33.8)\n12–39 Moderna45 3 3.64 0.79 –19.45 0.097 17.0 (6.8 –35.0)\n40+ Either511 15 2.30 0.95 –5.43 0.063 4.0 (2.1 –7.0)\n40+ Pfizer54 5 1.65 0.34 –7.31 0.509 3.3 (1.1 –7.6)\n40+ Moderna44 8 1.85 0.43 –6.85 0.373 4.6 (1.7 –10.1)\n17Verified Myocarditis and Pericarditis in the 0–7 Day Risk Interval\nCompared with Events on the Same Calendar Days Among Primary Series and Boosted Comparators\n1Comparison interval is 22– 42 days after booster dose.\n2Adjusted for VSD site, 5- year age group, sex, race/ethnicity, calendar date, and time since primary series.\n3“Either” includes heterologous and homologous primary -> booster doses. Product specific analyses include only homologous primar y-> booster doses. \n4Two additional cases were in the risk interval but were not included because there were no appropriate comparators. These cas es are included in the events/million dose calculation.Analysis\nAges VaccineEvents \ninRisk\nIntervalEvents in \nComparison \nInterval1Adjusted \nRate Ratio295%\nConfidence\nInterval2-Sided\nP-valueEvents/Million \nDoses\n1st\nBooster312–39 Either 30 10 1.90 0.91 –4.25 0.092 21.9 (14.8 –31.2)\n12–39 Pfizer 19 6 2.07 0.79 –6.05 0.146 22.8 (13.7 –35.6)\n12–39 Moderna46 3 1.36 0.33 –6.87 0.697 19.5 (8.4 –38.5)Verified Myocarditis and Pericarditis in the 0–21 Day Risk Interval\nCompared with Events on the Same Calendar Days Among Primary Series and Boosted Comparators\n18\n1Comparison interval is 22– 42 days after booster dose.\n2Adjusted for VSD site, 5- year age group, sex, race/ethnicity, calendar date, and time since primary series. \n3“Either” includes heterologous and homologous primary -> booster doses. Product specific analyses include only homologous primar y-> booster doses. \n4Two additional cases were in the risk interval but were not included because there were no appropriate comparators. These cas es are included in the events/million dose calculation.\n5Four additional cases were in the risk interval but not included because there were no appropriate comparators. These cases are included in the events/million dose calculation.\n6Three additional cases were in the risk interval but not included because there were no appropriate comparators. These cases areincluded in the events/million dose calculation.Analysis\nAges VaccineEvents \ninRisk\nIntervalEvents in \nComparison \nInterval1Adjusted \nRate Ratio295%\nConfidence\nInterval2-Sided\nP-valueEvents/Million \nDoses\n1st\nBooster312–39 Either 30 10 1.90 0.91 –4.25 0.092 21.9 (14.8 –31.2)\n12–39 Pfizer 19 6 2.07 0.79 –6.05 0.146 22.8 (13.7 –35.6)\n12–39 Moderna46 3 1.36 0.33 –6.87 0.697 19.5 (8.4 –38.5)\n40+ Either529 15 1.96 1.02 –3.88 0.044 11.0 (7.5 –15.4)\n40+ Pfizer515 5 3.01 1.06 –9.68 0.038 12.5 (7.5 –19.5)\n40+ Moderna69 8 1.28 0.42 –3.80 0.650 9.3 (4.8 –16.3)Verified Myocarditis and Pericarditis in the 0–21 Day Risk Interval\nCompared with Events on the Same Calendar Days Among Primary Series and Boosted Comparators\n19\nSummary: Preliminary Findings of RCA Monitoring for 1st\nBoosters \n•In weekly surveillance, the only safety signal has been for myocarditis/pericarditis \nin the 21 days after a 1stbooster dose.\n•No other safety signals in weekly monitoring of pre- specified outcomes. \n•Myocarditis/pericarditis differed between persons ages 12– 39 and 40+ years. \n•12–39 years: mostly myocarditis and myopericarditis with onset <7 days after 1stbooster.\n•40+ years: mostly pericarditis; cases more spread out in the 3 weeks after 1stbooster.\n•For persons ages 12– 39 years, rate ratios for myocarditis/pericarditis 0– 7 days \nafter 1stbooster dose were elevated.\n•Rate per million 1stbooster doses administered was not higher than after primary series dose \n2 mRNA COVID -19 vaccination. \n•For persons ages 40 years and older, rate ratios for myocarditis/pericarditis were elevated, but less so, in the 0– 7 and 0– 21 days after the 1\nstbooster dose \ncompared with persons ages 12– 39 years.\n•Surveillance is ongoing.\n20\ncdc.gov/coronavirusSafety update of 1stbooster mRNA \nCOVID -19 vaccination\nVaccine Adverse Event Reporting System (VAERS)\n&\nV-safe\nTom Shimabukuro, MD, MPH, MBA\nVaccine Safety Team\nCDC COVID- 19 Vaccine Task Force\n+co-managed by\nCDC and FDA\nVaccine Adverse Event \nReporting System\nhttp://vaers.hhs.govVAERS is the nation’s early warning system for vaccine safety\n22\nVAERS accepts reports from everyone\nKey strengths\nRapidly detects potential \nsafety problems \nCan detect rare adverse \neventsKey limitations\nPassive surveillance system\nInconsistent quality and completeness of information\nReporting biases\nGenerally, cannot determine cause and effectRegardless of the plausibility of the vaccine causing the event or the \nclinical seriousness of the event\n23\nU.S. reports to VAERS following 1stbooster mRNA COVID- 19 \nvaccination* (as of April 11, 2022) \n24* Among persons receiving Pfizer -BioNTech dose 3: children and adolescents ages 12– 15 years vaccinated during Jan 3 – April 11, 2022, and ages 16– 17 years vaccinated during Dec 9, 2021 –\nApril 11, 2022; adults ages ≥18 years vaccinated during September 22, 2021 –April 11, 2022. Among persons receiving Moderna boo ster doses, adults ages ≥18 years vaccinated during October \n20, 2021 –April 11, 2022. All reports received and processed as of April 11, 2022. \n†Doses of Pfizer -BioNTech dose 3 administered among children and adolescents ages 12 –15 years during January 6 –Apr 14, 2022; a dolescents ages 16– 17 years during Dec 9, 2021 –April 14, \n2022; adults ages ≥18 years during September 22, 2021 –April 14, 2022. Doses of Moderna dose 3 administered among adults ages ≥ 18 years during October 28, 2021 –April 14, 2022\n‡ Sex was not reported in approximately 2% of reports.Proportions by seriousness and sex were comparable to primary series\n•Most reports (90%) were non- serious\n•Most reports (65%) were among femalesDoses\nadmin†Total\nreportsMedian \nageMale‡\nn (%)Female‡\nn (%)Non -serious\nn (%)Serious\nn (%)\n93,118,318 52,063 53 years 17,281 (33) 33,692 (65) 47,014 (90) 5,049 (10)\nU.S. reports to VAERS following 1st\nbooster mRNA COVID -19 vaccination, \nby race and ethnicity * (as of April 11, 2021) Race and ethnicity n (%)\nNon -Hispanic White 25,508 (49)\nUnknown or not reported 14,787 (28)\nHispanic† 3,616 (7)\nNon -Hispanic Other 2,987 (6)\nNon -Hispanic Black 2,264 (4)\nNon -Hispanic Asian 1,764 (3)\nNon -Hispanic multiracial 561 (1)\nNon -Hispanic American\nIndian/Alaskan Native520 (<1)\nNon -Hispanic Native Hawaiian\nor Other Pacific Islander56 (<1)\nTotal 52,063* Among persons receiving Pfizer -BioNTech dose 3: children and adolescents ages 12 –15 years \nvaccinated during Jan 3 –April 11, 2022, and ages 16 –17 years vaccinated during Dec 9, 2021 –\nApril 11, 2022; adults ages ≥18 years vaccinated during September 22, 2021 –April 11, 2022. \nAmong persons receiving Moderna booster doses, adults ages ≥18 years vaccinated during October \n20, 2021 – April 11, 2022. All reports received and processed as of April 11, 2022. \n†Includes persons reported as of Hispanic ethnicity, but of unreported or unknown race.\n25\nMost frequently reported non- serious adverse events to VAERS following 1stbooster \nmRNA COVID -19 vaccination (47,014 total non- serious reports) * (as of April 11, 2022)\n26Rank Adverse event (not mutually exclusive) n (%)\n1 Headache 6,119 (13)\n2 Pyrexia 5,840 (12)\n3 Pain 5,783 (12)\n4 Fatigue 5,420 (12)\n5 Expired Product Administered 5,082 (11)\n6 Chills 4,836 (10)\n7 Product Storage Error 4,030 (9)\n8 Pain In Extremity 3,813 (8)\n9 Nausea 3,209 (7)\n10 Dizziness 2,982 (6)Non-serious reports (all reports) Non-serious reports (clinical outcomes)†\nRank Adverse event (not mutually exclusive) n (%)\n1 Headache 6,119 (13)\n2 Pyrexia 5,840 (12)\n3 Pain 5,783 (12)\n4 Fatigue 5,420 (12)\n5 Chills 4,836 (10)\n6 Pain In Extremity 3,813 (8)\n7 Nausea 3,209 (7)\n8 Dizziness 2,982 (6)\n9 Urticaria 2,966 (6)\n10 Lymphadenopathy 2,896 (6)\n* Among persons receiving Pfizer -BioNTech dose 3: children and adolescents ages 12 –15 years vaccinated during Jan 3 – April 11, 2022, and ages 16 –17 years vaccinated during Dec 9, \n2021 –April 11, 2022; adults ages ≥18 years vaccinated during September 22, 2021 –April 11, 2022. Among persons receiving Mode rna booster doses, adults ages ≥18 years vaccinated \nduring October 20, 2021 – April 11, 2022. All reports received and processed as of April 11, 2022. \n† Determined by subject matter expert consensus\nMost frequently reported serious adverse events to VAERS following 1stbooster \nmRNA COVID -19 vaccination (5,049 total serious reports) (as of April 11, 2022)\n27Rank Adverse event (not mutually exclusive) n (%)\n1 Covid -19 1,196 (24)\n2 Sars-Cov-2 Test Positive 997 (20)\n3 Dyspnoea 817 (16)\n4 Death 549 (11)\n5 Chest Pain 440 (9)\n6 Pyrexia 436 (9)\n7 Asthenia 435 (9)\n8 Condition Aggravated 396 (8)\n9 Fatigue 386 (8)\n10 Pain 369 (7)Serious reports (all reports) Serious reports (clinical outcomes)†\nRank Adverse event (not mutually exclusive) n (%)\n1 Covid -19 1,196 (24)\n2 Sars-Cov-2 Test Positive 997 (20)\n3 Dyspnoea 817 (16)\n4 Death 549 (11)\n5 Chest Pain 440 (9)\n6 Pyrexia 436 (9)\n7 Asthenia 435 (9)\n8 Fatigue 386 (8)\n9 Pain 369 (7)\n10 Cough 328 (7)\n* Among persons receiving Pfizer -BioNTech dose 3: children and adolescents ages 12 –15 years vaccinated during Jan 3 – April 11, 2022, and ages 16 –17 years vaccinated during Dec 9, \n2021 –April 11, 2022; adults ages ≥18 years vaccinated during September 22, 2021 –April 11, 2022. Among persons receiving Mode rna booster doses, adults ages ≥18 years vaccinated \nduring October 20, 2021 – April 11, 2022. All reports received and processed as of April 11, 2022. \n† Determined by subject matter expert consensus\n28Median age in myocarditis case reports is younger vs. pericarditis\nMale predominance observed for myocarditis case reports but not for pericarditisMyocarditis (n=110) Pericarditis (n=38)\nMedian age (IQR†) 23 (16– 36) 46 (25– 62)\nMedian time to symptom onset (IQR†) 3 (2– 4) 3 (1– 7)\nMale, n (%) / Female, n (%) 89 (81%) / 21 (19%) 18 (47%) / 20 (53%)U.S. reports to VAERS of myocarditis and pericarditis following 1stbooster \nmRNA COVID -19 vaccination, by age, time to symptom onset, and sex* \n(as of April 11, 2022) \n* Among persons receiving Pfizer -BioNTech dose 3: children and adolescents ages 12 –15 years vaccinated during Jan 3 – April 11, 2022, and ages 16 –17 years vaccinated during Dec 9, \n2021 –April 11, 2022; adults ages ≥18 years vaccinated during September 22, 2021 –April 11, 2022. Among persons receiving Mode rna booster doses, adults ages ≥18 years vaccinated \nduring October 20, 2021 – April 11, 2022. All reports received and processed as of April 11, 2022. \n†Interquartile range.\n29Most myocarditis \nreports among ages 12–29 years\nPericarditis reports distributed fairly evenly among age groups*\n024681012141618\n12 to 15 16 to 17 18 to 24 25 to 29 30 to 39 40 to 49 50 to 64 65+Verified reports to VAERS\nAge group, yearsMyocarditis or pericarditis following 1stmRNA COVID -19 booster \nvaccination among males , days 0– 7, by age group, VAERS\nPfizer, myocarditis Moderna, myocarditis Pfizer, pericarditis Moderna, pericarditis\n* Complicates estimation of reporting rates\n024681012141618\n12 to 15 16 to 17 18 to 24 25 to 29 30 to 39 40 to 49 50 to 64 65+Verified reports to VAERS\nAge group, yearsMyocarditis or pericarditis following 1stmRNA COVID -19 booster \nvaccination among males , days 0– 7, by age group, VAERS\nPfizer, myocarditis Moderna, myocarditis Pfizer, pericarditis Moderna, pericarditis\n30Most myocarditis \nreports among ages 12–29 years\nPericarditis reports distributed fairly evenly among age groups*\n* Complicates estimation of reporting rates\n31Most myocarditis \nreports among ages 12–29 years\nPericarditis reports distributed fairly evenly among age groups*\n* Complicates estimation of reporting rates024681012141618\n12 to 15 16 to 17 18 to 24 25 to 29 30 to 39 40 to 49 50 to 64 65+Verified reports to VAERS\nAge group, yearsMyocarditis or pericarditis following 1stmRNA COVID -19 booster \nvaccination among males , days 0– 7, by age group, VAERS\nPfizer, myocarditis Moderna, myocarditis Pfizer, pericarditis Moderna, pericarditis\n32Few reports among \nfemales of either condition\nBoth myocarditis and pericarditis reports distributed fairly evenly among age groups\n024681012141618\n12 to 15 16 to 17 18 to 24 25 to 29 30 to 39 40 to 49 50 to 64 65+Verified reports to VAERS\nAge group, yearsMyocarditis or pericarditis following 1stmRNA COVID -19 booster \nvaccination among females , days 0– 7, by age group, VAERS\nPfizer, myocarditis Moderna, myocarditis Pfizer, pericarditis Moderna, pericarditis\nReporting rates of myocarditis (per 1 million doses administered) among \nmales following 1stmRNA COVID -19 booster vaccination, by risk interval*\n41,670,922 1stmRNA COVID -\n19 booster vaccinations \nadministered in males*\nReporting rates exceed background incidence in ages 12 –29 years\nReporting rates highest in males ages 16 –17 years, \nfollowed by 12– 15 years\n* Among persons receiving Pfizer -BioNTech dose 3: children and adolescents ages 12 –15 years vaccinated during Jan 3 – April 11, 2022, and ages 16 –17 years vaccinated during Dec 9, \n2021 –April 11, 2022; adults ages ≥18 years vaccinated during September 22, 2021 –April 11, 2022. Among persons receiving Mode rna booster doses, adults ages ≥18 years \nvaccinated during October 20, 2021 – April 11, 2022. All reports received and processed as of April 11, 2022. Doses administered as of April 14, 2022. An estimated 1 –10 cases of \nmyocarditis per 100,000 person years occurs among people in the United States, regardless of vaccination status; adjusted for day 0–7 and 0 –21 risk periods, this estimated \nbackground is 0.2 to 2.2 per 1 million person risk period. 33Pfizer -BioNTech Moderna\nage group Days 0 –7 Days 0 –7\n12 to 15 17.2 N/A\n16 to 17 23.2 N/A\n18 to 24 5.4 12.1\n25 to 29 4.8 4.0\n30 to 39 1.5 1.5\n40 to 49 0.0 <1.0\n50 to 64 <1.0 0.0\n65+ <1.0 <1.0\nClinical outcomes of myocarditis and pericarditis following 1stmRNA \nCOVID -19 booster vaccination*\n93,118,318 total \nbooster doses \nadministered*\nPatients not \nhospitalized \nreceived outpatient \ncare\nPatients still recovering are \nstable or improving\n34* Doses of Pfizer -BioNTech dose 3 administered among children and adolescents ages 12 –15 years during January 6 –Apr 14, 2022; adolescents ages 16 –17 years during Dec 9, \n2021 –April 14, 2022; adults ages ≥18 years during September 22, 2021 –April 14, 2022. Doses of Moderna dose 3 administered am ong adults ages ≥18 years during October 28, \n2021 –April 14, 2022 Myocarditis \n(N=110)Pericarditis \n(N=38)\nHospitalized 90/110 (82%) 15/38 (39%)\nDischarged 90/90 (100%) 15/15 (100%)\nKnown outcomes 86/90 (96%) 14/15 (93%)\nRecovered from symptoms at \nlast follow up51/86 (59%) 10/14 (71%)\n35Smartphone -based active safety monitoring\nhttp:// cdc.gov/vsafe\nEnroll yourself or \nyour dependent \nafter any dose!\nActive safety monitoring for COVID -19 vaccines\nv-safe is a CDC smart phone -based monitoring program for COVID- 19 \nvaccine safety in the U.S.\n•Uses text messaging and web surveys to check in with vaccine recipients after \nvaccination\n•Can register at any time: after first, second, or third dose\n•Solicits participants' reports on how they feel after COVID -19 vaccination\n‒Local injection site reactions (i.e., pain, redness, swelling)\n‒Systemic reactions (i.e., fatigue, headache, joint pain)\n‒Health impacts (unable to perform normal daily activities, missed school or work, or received care) \n36\nPatterns of vaccination for 729,720 v -safe participants aged \n≥18 years who reported a booster dose\nModerna (%) Pfizer -BioNTech (%) Janssen (%) Total\nModerna 311,374 (94) 17,034 23,211 351,619\nPfizer -BioNTech 19,538 336,618 (95) 13,685 369,841\nJanssen 247 238 7,775 (17) 8,260\nTotal 331,159 353,890 44,671 729,720Primary series\nBooster\ndose\nData as of April 10, 2022. Includes participants who completed at least one survey in the first week after each dose (administered beginning \nSeptember 22, 2021 for Pfizer -BioNTech and October 20,2021 for Moderna and Janssen). 37\nDemographic summary of 729,720 v -safe participants aged \n≥18 years who reported a booster dose\nData as of April 10, 2022. Includes participants who completed at least one survey in the first week after each dose (administered beginning \nSeptember 22, 2021 for Pfizer -BioNTech and October 20,2021 for Moderna and Janssen). \nAbbreviations: AI/AN = American Indian/Alaska Native; NHPI = Native Hawaiian or other Pacific Islander; AA=African American.Characteristic % of participants\nSex\nFemale 62.8\nMale 36.4\nUnknown 0.8\nAge group (years)\n18–49 268,632\n50–64 189,735\n65–74 210,566\n75–84 56,051\n≥85 4,736Characteristic % of participants\nEthnicity\nHispanic or Latino 6.7\nNot Hispanic/ Latino 90.2\nUnknown 3.1\nRace\nAI/AN 0.4\nAsian 5.4\nBlack or AA 5.6\nNHPI 0.2\nWhite 82.9\nMultiracial 1.8\nOther 1.9\nUnknown 1.8\n38\nReactions and health impact events reported by v -safe participants aged ≥18 years at \nleast once in days 0– 7 after homologous Pfizer -BioNTech vaccination, by dose\nIncludes 336,618 participants who completed at least one survey in the first week after each dose, data collected during Sept emb er 22 –April 10, 2022 \n* Dose 2 compared to dose 3: statistically significant difference (p -value <0.05) using multivariable generalized estimating equ ations model that accounted for \nthe correlation between registrants and adjusted for demographic variables. 390102030405060708090100\nAny injection site\nreactionAny systemic reaction Any health impact Unable to perform\ndaily activitiesUnable to work Needed medical carePercentage\nDose 1 Dose 2 Booster* *\n**\n*\n*\nReactions and health impact events reported by v -safe participants aged 12– 17 years \nat least once in days 0– 7 after homologous Pfizer -BioNTech vaccination, by dose\nIncludes 3,694 participants who completed at least one survey in the first week after each dose, data collected during December 9, 2021– April 10, 2022 \n* Dose 2 compared to dose 3: statistically significant difference (p -value <0.05) using multivariable generalized estimating equ ations model that accounted for \nthe correlation between registrants and adjusted for demographic variables. 400102030405060708090100\nAny injection site\nreactionAny systemic reaction Any health impact Unable to perform\ndaily activitiesUnable to work or\nattend schoolNeeded medical carePercentage\nDose 1 Dose 2 Booster*\n*\n*\n*\n*\nReactions and health impact events reported by v -safe participants aged ≥18 years at \nleast once in days 0– 7 after homologous Moderna vaccination, by dose\nIncludes 311,374 participants who completed at least one survey in the first week after each dose, data collected during Octo ber20–April 10, 2022 \n* Dose 2 compared to dose 3: statistically significant difference (p -value <0.05) using multivariable generalized estimating equ ations model that accounted for \nthe correlation between registrants and adjusted for demographic variables. 410102030405060708090100\nAny injection site\nreactionAny systemic reaction Any health impact Unable to perform\ndaily activitiesUnable to work Needed medical carePercentage\nDose 1 Dose 2 Booster**\n*\n**\nSummary of the safety of 1stbooster \nmRNA COVID -19 vaccination\n42\nSummary\nVSD Rapid Cycle Analysis (RCA) monitoring \nThe only safety signal detected for any pre -specified outcome following 1stbooster dose has \nbeen for myocarditis/pericarditis in the 21 days after mRNA COVID- 19 vaccination\nMyocarditis/pericarditis differed between persons ages 12 –39 and 40+ years \n•12–39 years: mostly myocarditis and myopericarditis with onset <7 days after vaccination\n•40+ years: mostly pericarditis; cases more spread out in the 3 weeks after vaccination\nFor persons ages 12 –39 years, rate ratios for myocarditis/pericarditis 0 –7 days after 1st\nbooster dose were elevated\n•Rate per million 1stbooster doses administered was not higher than after dose 2 mRNA \nCOVID -19 vaccination \nFor persons ages 40 years and older, rate ratios for myocarditis/pericarditis were elevated, \nbut less so in the 0 –7 and 0– 21 days after the 1stbooster dose compared to persons ages 12 –\n39 years\n43\nSummary (cont.)\nVAERS monitoring (after 93 million 1stmRNA COVID -19 booster vaccinations in the United Sates)\nLocal and systemic reactions are most commonly reported following 1stbooster dose\n110 verified reports of myocarditis and 38 of pericarditis\n•Myocarditis reporting rates were highest among young males (ages 12– 29 years)\n‒Reporting rates for persons ages 12 –29 years following 1stbooster exceeded \nbackground, but were lower compared to post -dose 2 rates with primary series\n•Pericarditis reports were relatively rare, and distributed evenly among males and \nfemales and among the varied age groups\n•More myocarditis (82%) than pericarditis (39%) case patients were hospitalized \n‒Most hospitalized patients recovered from symptoms at time of follow up*\nV-safe monitoring \nNo unusual or unexpected findings or new safety concerns identified\n44 *Follow up varies based on timing of the report and healthcare records availability \nSummary (cont.)\n45Active surveillance in VSD and passive surveillance in VAERS suggests an increased risk of \nmyocarditis/pericarditis following the 1stmRNA COVID- 19 booster vaccination\n•For myocarditis, the findings are consistent with those observed with primary series vaccination, but the risk appears to be lower following the 1\nstbooster dose compared \nto dose 2 of primary series\n‒Risk of myocarditis is highest in younger males with onset clustering within 0 –7 \ndays of 1stbooster vaccination\n‒Pericarditis is less common, more evenly distributed between males and females, and more evenly distributed across age groups\nLocal and systemic reactogenicity and health impacts appear similar or attenuated for 1st\nmRNA COVID- 19 booster vaccination compared to dose 2 of primary series\nMonitoring is ongoing  \nAcknowledgments\nVAERS team\nCISA team\nVSD team\nCOVID -19 Vaccine Task Force Data Monitoring \nand Reporting Group\nCDC Immunization Safety Office\nFDA/Center for Biologics Evaluation and Research\nState and local health departments \nHealthcare providers and other stakeholders \nreporting to VAERS\nV-safe team\nV-safe participants\nAnne Hause\nJames Baggs\nPaige Marquez\nIsaac McCullum\nBicheng Zhang\nTanya Myers\n46Kaiser Permanente Northern California\n•Nicky Klein, Laurie Aukes, Berwick Chan, Bruce Fireman, Kristin Goddard, Ned Lewis, Karen Nunley, Pat Ross, Arnold \nYee, Ousseny Zerbo, Nandini Bahkshi\nMarshfield Clinic Research Institute\n•Jim Donahue, Ed Belongia, Tom Boyce, Kayla Hanson, Burney Kieke, Dave McClure, Erica Scotty\nCDC Immunization Safety Office\n•Eric Weintraub, Tat’Yana Kenigsberg, Mike McNeil, Jonathan Duffy, Frank Destefano, Tanya Myers, Tom \nShimabukuro, Matt Oster\nVSD Sites\n•HealthPartners Institute, Minneapolis, Minnesota\n•Kaiser Permanente Colorado, Denver, Colorado\n•Kaiser Permanente Northwest, Portland, Oregon\n•Kaiser Permanente Southern California, Los Angeles, \nCalifornia\n•Kaiser Permanente Washington, Seattle, Washington\n•Denver Health, Denver, Colorado\nFor more information, contact CDC\n1-800- CDC- INFO (232- 4636)\nTTY:  1 -888- 232- 6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.\nThank you!", "summary": "cdc.gov/coronavirusSafety update of 1stbooster mRNA       COVID -19 vaccination Advisory Committee on Immunization Practices  (ACIP) April 20, 2022 Nicola Klein, MD, PhD Kaiser Permanente Vaccine Study Center Kaiser Permanente Northern CaliforniaTom Shimabukuro, MD, MPH, MBA Vaccine Safety TeamCDC COVID- 19 Vaccine Task Force Safety Surveillance of 1stBooster Doses in the Vaccine  Safety Datalink Nicola Klein, MD, PhD Kaiser Permanente Vaccine Study Center Kaiser Permanente Northern…", "source_url": "https://www.cdc.gov/acip/evidence-to-recommendations/covid-19-second-booster-dose-etr.html", "pdf_url": "https://www.cdc.gov/acip/media/pdfs/2024/09/03-COVID-Klein-Shimabukuro-508.pdf", "case": "acip", "sub_case": "other", "tags": ["acip", "cdc", "vaccines", "other"], "page_count": 47}
{"title": "03 Pneumococcal Self 508", "content": "Public\nInterim Results from the PNEUMO Study\n. \nPneumococcal pNeumonia Epidemiology, Urine serotyping, and \nMental Outcomes study\nFebruary 29, 2024\nStudy Leadership\nWesley H. Self, MD\nVanderbilt UniversityJ. Jackson Resser , MS\nVanderbilt UniversityKelly D. Johnson, PhDMerck & Co., Inc.\n1 Funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USANadine Rouphael , MD\nEmory University\nPublic\nPNEUMO study overview\n•Adults 18+ years hospitalized with \ncommunity acquired pneumonia (CAP)Target \nPopulation\n•Multi -country, prospective, population -\nbased active surveillance studyDesign\n•Estimate pneumococcal pneumonia \nincidence and serotype prevalence (using \nMerck PCV15 and V116 SSUADs), with \nlongitudinal evaluation of functional status, quality of life and costObjectives►Incidence hospitalized pneumococcal CAP\n►Incidence hospitalized PCV15-  and\nV116 - type pneumococcal CAP\n►Direct medical cost\n►Work loss\n►Functional status \n►Cognitive status \n►Quality of Life (EQ -5D)Up to 6 \nmonths \npost -\ndischarge\n2\nPublic\nPneumonia surveillance  with prospective, real -time enrollment of \nadults hospitalized with CAP (including HCAP)\nHCAP, healthcare associated pneumonia US PNEUMO sites: enrollment Sept 2018 - present\nNashville, Tennessee\n(2 hospitals) Atlanta, Georgia\n3\nPublicEligibility criteria\nInclusion  Criteria\n1.Age ≥ 18 years  old\n2.Hospitalized\n3.Clinical signs and/or  symptoms of an acute  respiratory  illness (e.g., new  shortness of breath,  cough)\n4.Clinical signs and/or  symptoms of an acute  infection (e.g., fever,  leukocytosis)\n5.Radiologic  evidence  of pneumonia  interpreted  by a radiologist  (x-ray or CT) \nExclusion  Criteria\n1.Prior enrollment  in this study  within  the past  30 days  (to avoid  multiple  enrollments for same  episode  of \npneumonia).\n2.Development  of pneumonia  >72 hours  after  hospital admission  \n3.Inability  to obtain  consent  within  72 hours  of hospital admission  \n4.Inability  or unwillingness of the patient  to provide  a urine  sample  within  72 hours  of hospital admission .\n5.Non -pneumonia  illness completely  explains the patient’s  acute  symptoms.  4\nPublic\nTests for S. pneumoniae\n•Urine collection from patients at enrollment\n    (1) BinaxNow pneumococcal urinary antigen test (local testing by research team)\n   \n (2) Serotype- specific urinary antigen detection (SSUAD) assays:\n•Developed and performed by Merck laboratory\n•30 serotypes: \n•1, 3, 4, 5, 6A*, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15A, 15C#, 16F, 17F, 18C, 19A, 19F, 20A, 22F, \n23A, 23B, 23F, 24F, 31, 33F, 35B \n•All serotypes in PCV15, PCV20, and V116 included except 15B\n•Results of clinically -obtained bacterial cultures:\n•Sterile sites: blood, pleural fluid, BAL fluid, CSF, synovial fluid\n•Non -sterile sites: high-quality respiratory samples (>25 WBC, <10 epi) \n•sputum, endotracheal aspirate\n5* assay for serotype 6A has cross- reactivity with serotype 6C\n# assay for serotype 15C has mild cross- reactivity with serotype 15B\nPublic\nHospitalized adults screened for \neligibility\n(n = 5,385)\nEnrolled: adults hospitalized with \ncommunity acquired pneumonia (CAP)\n(n = 3,278)\nAnalyzed\n[All-cause CAP population]\n(n = 2,917)\nS. pneumoniae detected\n[Pneumococcal CAP population]\n(n = 352)S. pneumoniae not  detected\n[Non -pneumococcal CAP]\n(n = 2,565)\nS. pneumoniae culture positive \nfrom normally sterile site\n[Invasive pneumococcal CAP] \n(n = 51)S. pneumoniae detected outside \nnormally sterile site only\n[Non -invasive pneumococcal CAP] \n(n = 301)Not enrolled (n =2,107)\nEnrolled, not analyzed (n = 361)\n•No radiographic evidence of pneumonia (n=235)\n•Urine not tested by SSUAD (n = 114)  \n•Patient withdrew (n = 12)Enrolled Patients\n12.1%\npneumococcal\nprevalence\n85.5%\nof pneumococcal pneumonia\nwas non- invasive\nPublicPatient Characteristics: Demographics\nCharacteristic Pneumonia with \nS. pneumoniae detected \n(n= 352)Pneumonia without \nS. pneumoniae detected\n(n= 2565)P-value\nAge in years, median (IQR) 60.3 (50.6, 70.2) 60.5 (46.8, 70.2) 0.34\nAge category, n (%) 0.01\n18-49 years 85 (24.1%) 767/2564 (29.9%)\n50-64 years 141 (40.1%) 817/2564 (31.9%)\n≥65 years 126 (35.8%) 980/2564 (38.2%)\nFemale sex assigned at birth, n (%) 167/350 (47.7%) 1147/2558 (44.8%)\nRace, n (%) <0.01\nWhite 198 (56.2%) 1771 (69.0%)\nBlack 145 (41.2%) 703 (27.4%)\nAsian 1 (0.3%) 38 (1.5%)\nAmerican Indian/Native \nAlaskan2 (0.6%) 14 (0.5%)\nNative Hawaiian/Pacific Islander2 (0.6%) 6 (0.2%)\nOther 6 (1.7%) 54 (2.1%)\nEthnicity, n (%) 0.95\nNot Hispanic 328 (93.2%) 2394 (93.3%)\nHispanic 14 (4.0%) 94 (3.7%)\nUnknown 10 (2.8%) 77 (3.0%)7\nPublic\nCharacteristic Pneumonia with \nS. pneumoniae detected \n(n= 352)Pneumonia without \nS. pneumoniae detected\n(n= 2565)P-value\nType of home before illness, n (%) 0.27\nCommunity dwelling 320 (90.9%) 2382 (92.9%)\nNursing Home 6 (1.7%) 43 (1.7%)\nAssisted Living 6 (1.7%) 33 (1.3%)\nRehabilitation hospital 1 (0.3%) 13 (0.5%)\nSchool housing 0 (0.0%) 0 (0.0%)\nHomeless/shelter 12 (3.4%) 40 (1.6%)\nOther 3 (0.9%) 33 (1.3%)\nUnknown 4 (1.1%) 21 (0.8%)\nEver regularly smoked tobacco, n (%) 205/349 (58.7%) 1232/2554 (48.2%) <0.01\nAlcohol use >3 days/week, n (%) 30/348 (8.6%) 145/2543 (5.7%) 0.03\nUse of opioids at least weekly, n (%) 68/339 (20.1%) 438/2462 (17.8%) 0.31\nInteracts with child <5 years old at \nleast once per week, n (%)122/340 (35.9%) 682/2468 (27.6%) <0.01\nLives with children, n (%) 83/346 (24.0%) 517/2534 (20.4%)Patient Characteristics: Social History\n8\nPublic\nCharacteristic Pneumonia with \nS. pneumoniae detected \n(n= 352)Pneumonia without \nS. pneumoniae detected\n(n= 2565)P-value\nChronic medical conditions, n (%)\nDementia 11/349 (3.2%) 65/2528 (2.6%) 0.362\nCOPD 97/346 (28.0%) 487/2510 (19.4%) <0.001\nAsthma 72/346 (20.8%) 474/2518 (18.8%) 0.413\nHeart failure 61/340 (17.9%) 446/2509 (17.8%) 0.824\nPrior MI 37/344 (10.8%) 231/2525 (9.1%) 0.359\nPrior stroke 38/347 (11.0%) 255/2516 (10.1%) 0.651\nEnd stage kidney disease with \nchronic kidney replacement14/342 (4.1%) 125/2515 (5.0%) 0.424\nDiabetes mellitus 82/348 (23.6%) 684/2525 (27.1%) 0.159\nChronic liver disease 30/343 (8.7%) 173/2508 (6.9%) 0.254\nImmunosuppression 72/343 (21.0%) 529/2499 (21.2%) 0.983\nSolid organ cancer 80/348 (23.0%) 589/2501 (23.6%) 0.981\nHematologic cancer 30/346 (8.7%) 193/2511 (7.7%) 0.598\nSolid organ transplant 25/347 (7.2%) 205/2528 (8.1%) 0.545\nPregnant 0/348 (0.0%) 22/2533 (0.9%) 0.081\nObesity with body mass index \n>30 kg/m289/355 (25.9%) 1009/2479 (40.7%) <0.001Patient Characteristics: Chronic Medical Conditions \n9\nPublic\nCharacteristic Pneumonia with \nS. pneumoniae detected \n(n= 352)Pneumonia without \nS. pneumoniae detected\n(n= 2565)P-value\nReceived antibiotics for current illness before \nhospitalization, n (%)71/328 (21.6%) 613/2297 (26.7%) 0.05\nDuration of acute illness prior to hospital admission [days], median (IQR)2.6 (1.3, 5.0) 2.7 (1.1, 5.7) 0.36\nCURB- 65* score at hospital admission, n (%) 0.17\n0 (low risk) 123/345 (35.7%) 943/2523 (37.4%)\n1 (low risk) 126/345 (36.5%) 869/2523 (34.4%)\n2 (moderate risk) 60/345 (17.4%) 547/2523 (21.7%)\n3 (high risk) 31/345 (9.0%) 150/2523 (5.9%)\n4 (high risk) 5/345 (1.4%) 14/2523 (0.6%)\n5 (high risk) 0/345 (0.0%) 0/2523 (0.0%)\nTiming of Enrollment <0.01\nBefore COVID- 19 in US (October 2018 – \nFebruary 2020)231/345 (67.0%) 1249/2519 (49.6%)\nAfter COVID- 19 in US (March 2020 – \nOctober 2022)114/345 (33.0%) 1270/2519 (50.4%)Patient Characteristics: Acute Illness\n10* CURB -65: pneumonia severity scoring system, consisting of the following variables: confusion, uremia, respiratory rate, blood pressure, age >65\nPublic\nBinaxNOW\n125 patients positive\nCultures\n56 patients positive44 53 SSUAD\n283 patients positive 199\n1117523352 Patients with ≥1 Positive Pneumococcal Test\n12Percentage of Pneumococcal Serotype Detections\n14.6%\n9.8%\n7.0%\n6.0%5.7%5.4%5.1%4.7%4.1%3.5%3.2%2.8%2.2%1.9%1.6%1.3%0.9% 0.3% 0.0%\nn=46 n=31 n=22 n=19 n=18 n=17 n=16 n=15 n=13 n=11 n=10 n=9 n=7 n=6 n=5 n=4 n=3n=1n=0\n3 22F 19A 35B 9N 19F 23A 11A 23B 7F, 8, \n17F, 316A/C 16F, \n20A1, 5 9V, 15C 15A 33F 4, 6B, \n24F14, 10A, \n12F18C,  \n23F\nSerotype316 serotypes detected by SSUAD (denominator) among 283 unique patients\n13Vaccine Category Pneumococcal serotypes% of serotypes in adults \nhospitalized with CAP \n(n=2917)\nV116 (21 serotypes) 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15C, 16F, 17F, 19A, 20A, 22F, 23A, 23B, 24F, 31, 33F, 35B 9.3%\nPCV20  (19 serotypes; serotype 15B not tested) 1, 3, 4, 5, 6A, 6B, 7F, 8, 9V, 10A, 11A, 12F, 14, 18C, 19A, 19F, 22F, 23F, 33F 6.7%\nPCV15  (15 serotypes) 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, 33F 5.8%\nV116 and not PCV15 or PCV20 (11 serotypes) 9N, 15A, 15C, 16F, 17F, 20A, 23A, 23B, 24F, 31, 35B 4.1%8.0%11.3%\n8.7%\n4.7%8.4%\n6.9%\n4.0%7.3%\n5.8%\n4.0%4.8%\n3.1%\n0%2%4%6%8%10%12%\n18-49 years old (n=852) 50-64 years old (n=958) 65+ years old (n=1107)% of patients with ≥1 serotype in categoryV116 PCV20 PCV15 11 unique V116 serotypesPercentage of Pneumococcal Serotype by Vaccine in Adults Hospitalized with CAP\nPublic\nConclusions\n•Pneumococcal CAP remains a major cause of adult hospitalizations\n•SSUAD assays greatly increase S. pneumoniae detection over traditional testing\n•Among adults hospitalized with CAP:\n•12.1% with S. pneumoniae detected\n•9.3% with a pneumococcal serotype in V116\n•4.1% with a serotype unique to V116 (not PCV15 or PCV20)\n•Most commonly detected serotypes unique to V116: 35B, 9N, 23A, 23B\n14", "summary": "Public Interim Results from the PNEUMO Study .  Pneumococcal pNeumonia Epidemiology, Urine serotyping, and  Mental Outcomes study February 29, 2024 Study Leadership Wesley H. Self, MD Vanderbilt UniversityJ. Jackson Resser , MS Vanderbilt UniversityKelly D. Johnson, PhDMerck & Co., Inc. 1 Funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USANadine Rouphael , MD Emory University Public PNEUMO study overview •Adults 18+ years hospitalized with  community acquired…", "source_url": "https://www.cdc.gov/acip/evidence-to-recommendations/pcv21-non-risk-based-adults-19-49-etr.html", "pdf_url": "https://www.cdc.gov/vaccines/acip/meetings/downloads/slides-2024-02-28-29/03-Pneumococcal-Self-508.pdf", "doc_date": "2024-02-28", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 14}
{"title": "03 Rabies Rao 508", "content": "National Center for Emerging and Zoonotic Infectious Diseases\nSummary of Evidence to Recommendations \nFramework for Rabies Pre -Exposure Prophylaxis Vote\nAdvisory Committee on Immunization Practices\nFebruary 24, 2021Agam Rao, MD\nCAPT, US Public Health Service\nPoxvirus and Rabies Branch\nCenters for Disease Control and Prevention\nRabies antibody response\n▪Target response, i.e., ≥ minimum antibody titer, 0.5 IU/mL, regardless of \nseries\n–Children\n–Pregnant women\n–Persons ≥ 65 years of age\n▪Persons with altered immunity\n–Efficacy can be a concern\n–Titer check after primary series (and boosters until ≥ 0.5 IU/mL) \nRabies vaccines licensed in U.S.\n▪Been used in the U.S. for decades\n▪No change in favorable safety profileBiologicProduct \nnameManufacturer Administration Potency\nHuman \ndiploid cell \nvaccine \n(HDCV)Imovax Sanofi Pasteur intramuscularly≥2.5 IU of \nrabies \nantigen\nPurified \nchick \nembryo cell \nvaccine \n(PCECV)RabAvertBavarian \nNordicintramuscularly≥2.5 IU of \nrabies \nantigen\nEstimated* PrEP use in the United States\n▪Doses:  170,000 including 500 booster doses\n▪Categories of people receiving PrEP :  60,535 / year\n–Travelers and “other risk groups”: 41,117\n–Veterinary technicians:  13,860\n–Veterinary students:  3,500\n–Animal control: 1,178\n–Rabies laboratory personnel: 480\n–Wildlife biologists:  400* Mathematical model based on \nworkforce statistics produced by \nBureau of Labor Statistics and market \nresearch provided by Bavarian Nordic\nAdherence to ACIP PrEP recommendations*\n▪Veterinary students:  100% (required for clinics)\n▪Laboratory personnel:  100% (required)\n▪Animal control:  78.5%\n▪Veterinary technicians/staff:  69.3% (in other published studies, 30 -40% adherence)\n▪Wildlife biologists:  ~50%\n▪Other risk groups:  ?\n▪Travelers:  ?\n*Some results from unpublished CDC data; Blanton \net al.\nIncludes data obtained from ~2,000 persons     \nSurvey sent to members of professional  \norganizations who were certified providers and \nwere likely more compliant with the ACIP recs \nthan persons not captured by the survey\nEtRfor policy question #1:  Primary \nimmunogenicity\nPrEP policy question #1\nPolicy question: Should a two dose pre -exposure prophylaxis ( PrEP ) series \ninvolving HDCV* or PCECV †IM [0, 7 days] replace the 3 dose series IM[0, 7, \n21/28 days] for all those for whom rabies vaccine PreP is recommended?\nPopulation Persons for whom rabies vaccine PrEP is recommended\nIntervention [0, 7 days] rabies vaccine PrEP schedule\nComparison [0, 7, 21/28 days] rabies vaccine PrEP schedule\nOutcome Primary immunogenicity \n*Human diploid cell vaccine\n† Purified chick embryo cell vaccine\nProblem: Rabies and PrEP\n▪Rabies is nearly always fatal\n▪PrEP is important component of preventing human rabies in U.S.\n▪PrEP critically important to some persons\n–Unusual exposures (e.g., aerosolized) or high concentration virus\n–Unrecognized exposures\n–Frequent exposure to potentially rabid animals\n–Travel abroad to canine -rabies endemic regions without quick PEP access\nPrimary immunogenicity of PrEP for rabies\n▪Rabies modern cell culture vaccines are effective\n▪ACIP has recommended PrEP for decades\n▪Noncompliance among some for whom it is recommended\n–Out-of-pocket costs\n–Some occupations do not require it\n–Insufficient time to complete 3 -dose series before international travel\nEtR:  Policy question #1\nDomains WG interpretation\nBenefits:  How substantial are the desired \nanticipated effectsMinimal; 100% of people seroconvert for proposed and \nfor previous schedule\nHarms:  How substantial are undesirable \nanticipated effects?Minimal; No expected safety concerns\nBenefit / Harm:  Do desirable effects outweigh \nundesirable effects?Favors both\nOverall certainty for evidence:  effectiveness Moderate certainty of evidence (Level 2) due to \nconcerns for risk of bias\nPrEP costs\n▪Reimbursement price for vaccine \ndose:  $331*(Source: CMS/ASP)\n▪Additional costs are variable \ndepending on location PrEP is \nadministered \n▪We estimate $1100 -$3500 for \nPrEP series\n(3 vaccines + additional costs)\nFigure: Location of pre -exposure vaccine administration by occupation \nin the United States; not shown is PrEP received in Emergency \nDepartments which was the location for PrEP in 2% of respondents \n(Source:  Blanton et al, unpublished data from CDC survey)\nProportion of PrEP costs that are out -of-pocket\nVaccination indication # reporting \ninsurance would \ncover at least part \nof cost\nBooster       Titer#  reporting \nemployer would \ncover at least \npart of cost\nBooster       Titer# reporting \nEITHER would \ncover at least part \nof the cost\nBooster      Titer\nVeterinary professionals 25% 25% 20% 40% 25% 30%\nAnimal control 50% 40% 54% 20% 60% 60%\nAnimal rehabilitationists 25% 33% 12% 20% 25% 40%\nSource:  Unpublished CDC data; Blanton et al\nEtR:  Policy question #1\nDomains WG interpretation\nTarget population sentiments:  uncertainty about \nor variability in how much people value outcomes?No:  Target population values “protection” from rabies \nand there is likely no important variability\nAcceptability to stakeholders? Yes:  Shorter schedule preferred by patients & providers\nReasonable and efficient allocation of resources? Yes:  Cost savings and because rabies vaccine shortages \nhave occurred in U.S.\nImpact on equity? Probably reduced because of decreased costs\nFeasible to implement? Yes: Shorter series than current series\nEtR:  Policy question #1\nDomains WG interpretation\nTarget population sentiments:  Does the target \npopulation feel desirable effects are large relative \nto undesirable effectsProbably yes\n•Data supports high costs incurred by PrEP\nrecipients\n•Persons who should receive PrEP for travel are \nknown to not receive it because <21 days from \nclinic appointment to travel\nBalance of Consequences\nUndesirable                                        Undesirable Balance between \nconsequences clearly                       consequences probably               desirable and undesirable\noutweigh desirable                           outweigh desirable                       consequences is closely \nconsequences in most                      consequences in most                 balanced or uncertain\nsettings settings\nDesirable consequences Desirable consequences             There is insufficient evidence\nprobably outweigh clearly outweigh                           to determine the balance of\nundesirable consequences undesirable consequences          consequences\ninmost settings in most settingsX\nProposed recommendation for vote\nACIP recommends a 2 -dose [0, 7 days] intramuscular \nrabies vaccine series in immunocompetant persons \n>= 18 years of age for whom rabies vaccine pre -\nexposure prophylaxis ( PrEP ) is indicatedRecommendation\nEtRfor policy question #2: Long -term \nimmunogenicity \nPrEP policy question #2\nPolicy question: Should an IM booster dose of rabies vaccine (*PCECV or \n†HDCV) be recommended as an alternative to a titer check no sooner than \nday 21 and no later than 3 years after the two dose pre -exposure prophylaxis \n(PrEP ) series IM [0, 7 days] for those in the #3 risk category of people who \nreceive PreP ?\nPopulationPersons in the #3 risk category for whom rabies vaccine PrEP is \nrecommended\nInterventionDay 21 -year 3 rabies vaccine booster after [0, 7 days] rabies \nvaccine PrEP schedule\nComparisonNo rabies vaccine booster after [0, 7 days] rabies vaccine PrEP\nschedule\nOutcome Long -term immunogenicity\n*Human diploid cell vaccine\n† Purified chick embryo cell vaccine\nProblem: Long -term immunogenicity for rabies\n▪Immunology suggests that anamnestic response to an exposure occurs\n▪WHO approved 2 -dose series (no booster or titers)\n▪Rabies is nearly 100% fatal\n▪WG opted for most cautious route to ensure long -term immunogenicity for [0, 7 \ndays] series\n–Strong data for long -term immunogenicity only exists for up to 3 years\n–Data shows that titer at ≥ 1 year, is marker of long -term immunogenicity\n–WG proposed titer at 1 -3 years (and boost accordingly) OR\n–Booster no sooner than day 21 and no later than year 3\nLong -term immunogenicity reported in recently \npublished article*\n▪6 persons who received [0, 7 days] IM series, were evaluated after 10 -11 \nyears \n–3 male; 3 female\n–Ages 34 -46\n–5 had titers ≥ 0.5 IU/mL\n–All had 4 -fold increase in titers after booster\n▪More data expected about long -term immunogenicity of 2 -dose series because \nWHO recommendations made in 2018\n*De Pijper et al, Long -term memory response after a single intramuscular rabies booster vaccination, 10 -24 \nyears after primary vaccination. Journal of Infectious Diseases.  Epub January 2021\nEtR:  Policy question #2\nDomains WG interpretation\nBenefits:  How substantial are the desired \nanticipated effectsModerate\n•Booster at day 21 is equivalent to current 3 -dose \nseries and is known to provide long -term \nimmunogenicity \n•100% of subjects mounted anamnestic response to \nbooster at 1 -3 years\nHarms:  How substantial are undesirable \nanticipated effects?Minimal; No expected safety concerns\nBenefit / Harm:  Do desirable effects outweigh \nundesirable effects?Favors intervention\nOverall certainty for evidence:  effectiveness Low certainty of evidence (Level 3)\nEtR:  Policy question #2\nDomain WG interpretation\nTarget population sentiments:  Does the target \npopulation feel desirable effects are large relative \nto undesirable effectsProbably yes\n•Stakeholders want to avoid acquiring high -stakes \ninfection\n•Booster provides reassurance that outweighs any \ninconvenience\nTarget population sentiments:  uncertainty about \nor variability in how much people value outcomes?No:  Target population values “protection” from rabies \nand there is likely no important variability\nAcceptability to stakeholders? Yes:  Stakeholders accustomed to accommodating third \ndose of rabies vaccine and will find it acceptable to \nhave booster as an option\nReasonable and efficient allocation of resources? Yes:  Cost savings\nCosts of titer compared to booster \n▪Titer:  Cost ~$50 -$75* + cost of blood draw / clinic appointment\n▪Booster:  ~$331 for cost of booster + additional costs\n*KSU website and word of mouth\nEtR:  Policy question #2\nDomains WG interpretation\nImpact on equity? Don’t know:  some PrEP costs are out -of-pocket; \nbecause titer is offered as option, inequity could be \nresolved by choosing that option\nFeasible to implement? Yes: Administrators could opt to schedule booster dose \nat the time of primary vaccination\nBalance of Consequences\nUndesirable                                        Undesirable Balance between \nconsequences clearly                       consequences probably               desirable and undesirable\noutweigh desirable                           outweigh desirable                       consequences is closely \nconsequences in most                      consequences in most                 balanced or uncertain\nsettings settings\nDesirable consequences                   Desirable consequences             There is insufficient evidence\nprobably outweigh                             clearly outweigh                           to determine the balance of\nundesirable consequences               undesirable consequences          consequences\nin most settings                                  in most settings\n\nProposed recommendation for vote\nACIP recommends an intramuscular booster dose of rabies \nvaccine, as an alternative to a titer check, for \nimmunocompetent persons >=18 years who have sustained and \nelevated risk for only recognized rabies exposures (i.e., those in \nrisk category #3 of rabies PrEP recommendations table).  The \nbooster dose should be administered no sooner than day 21 \nbut no later than 3 years after the 2 -dose PrEP series. Recommendation\nClinical guidance scenarios\nTime (in years)Days [0, 7 days]2-dose PrEP\nYear 3Rabies \nexposure\nTo be cautious:\nPEP = RIG + vaccine IM[0, 3, 7, 14 days]No titer or \nbooster\nClinical guidance scenarios\nTime (in years)Days [0, 7 days] 2-dose PrEP\nYear 3Traveling againNo titer or \nboosterThese situations currently are handled \non case -by-case basis \nAcknowledgements\n▪Rabies WG\n▪Ryan Wallace\n▪Jesse Blanton\n▪Doug Campos -Outcalt\n▪Rebecca Morgan\n▪Florence Whitehill\n▪Jessica MacNeil\n▪Whitni Davidson\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the \nofficial position of the Centers for Disease Control and Prevention.\nNational Center for Emerging and Zoonotic Infectious Diseases\nDivision of High -Consequence Pathogens and PathologyQuestions?\nImplications of proposed changes\nRisk \ngroupPopulation Primary \nimmunog\nenicityImplications Long -term \nimmunogenicityImplications\n#1 Research laboratorians\nDiagnostic laboratorians\n#2 Bat biologists\n#3Animal care professionals in \nterrestrial rabies regions\nAnimal care professionals in \nnon -terrestrial rabies regions, \nstudents, spelunkers, \npersistent travelers\nShort -term animal care \nprofessionals and persons \nwithout sustained risk for \nrabiesTiter every 6 months\nIM [0, 7 \ndays]Fewer vaccine doses \nbut equivalent \nefficacyMakes sense to \nconsider all \nlaboratorians equallyTiter check ever 6 \nmonths1\nTiter check every 2 \nyears2No change\nNo change\nFewer vaccine doses \nand/or  fewer titer checks\nSame number of vaccine \ndoses OR instead of 3rd\nvaccine, a titer\nNo additional vaccine \nand no titersTiter once (1 -3 \nyears after \nprimary series)\nOR\nBooster no sooner \nthan day 21 and no \nlater than year 3\nPrEP Policy Question #1\nTable 3a: Summary of Randomized Control Trial Studies Reporting Outcome\nAuthors last \nname, pub \nyearAge (years) N \ninterventionN \ncomparisonVaccine Risk Ratio \n[95% CI]Study limitations \n(Risk of Bias)\nEndy , 2019 Mean 32.4, \nRange 18 -5922 24 PCEC, IM, ID 1.00 \n[0.89, 1.12]Some concerns1\nSoentjens , \n2019Median 29.0, \nRange NR242 240 HDCV, ID 1.00 \n[0.99, 1.01]Some concerns2\n1Allocation concealment not reported. Study did not blind participants or healthcare personnel; however, unlikely that co -interve ntions would \nhave influenced the outcome.\n2Method of randomization and allocation not reported. Study did not blind participants or healthcare personnel; however, unlik elythat co -\ninterventions would have influenced the outcome .\nPrEP Policy Question #1\nTable 3b: Summary of Observational Studies Reporting Outcome\nAuthors last name, pub \nyearAge (years) N \ninterventionN \ncomparisonVaccine Risk Ratio [95% \nCI]1Study limitations (Study \nquality2)\nAjjan , 1989 Mean 22, Range 19 -41 72 69 HDCV, IM 1.00 [0.97, 1.03] 9/9 No concerns\nArora, 2004 Mean 26.2, NR 44 44 HDCV, IM 1.00 [0.96, 1.04] 9/9 No concerns\nBriggs, 1996 NR 146 146 HDCV, IM 1.00 [0.99, 1.01] 9/9 No concerns\nCramer 2016 Mean 36.7, SD 12.9 371 364 PCEC, IM 0.99 [0.98, \n1.01]47/9 Minimal concerns\nHacibektasoglu , 1992 Mean 20, Range 18 -24 30 30 HDCV, IM 0.90 [0.79, 1.03] 9/9 No concerns\nJaijaroensup, 1999 NR, Range 17 -22 138 129 PCEC, IM, ID 0.94 [0.87, \n1.02]49/9 No concerns\nKitala, 1990 NR 37 37 HDCV, IM 1.00 [0.95, 1.05] 8/9 Minimal concerns\nRecuenco, 2017 Median 41.0, Range 20 -\n6260 59 PCEC, IM, ID 1.00 [0.96, 1.05]49/9 No concerns\nSabchareon, 1999 Mean 10, \nSD 1.33190 190 HDCV, IM 1.00 [0.99, 1.01] 7/9 Minimal concerns\nVodopija , 1986 NR 49 46 HDCV, PCEC, \nIM1.00 [0.94, 1.06]49/9 No concerns\n1Data from observational studies, where intervention and comparison data were taken from the same people at different time poi nts, were analyzed using M -H Risk Ratio \nrandom effects procedure.  Due to unavailable raw data on pairing, a matched analysis was not possible.\n2Study quality for observational studies was assessed using the Newcastle Ottawa Scale.\n3Age for total study population was not reported in this paper. Numbers in this cell are from the study arm from which data we re extracted.\n4Studies contained multiple arms relative to the analysis. Risk ratio reflects pooled analysis from eligible arms. \nPrEP Policy Question #2\nTable 3: Summary of Studies Reporting Outcome\nAuthors \nlast name, \npub yearAge (years) N intervention N comparison Comparator \nvaccineRisk Ratio \n[95% CI]Study limitations (Study \nquality3)\nEndy , 2019 Mean 32.4, \nRange 18 -5920 No comparison1PCEC, IM Not able to \ncalculate28/9 Minimal concerns\nSoentjens , \n2019Median 29.0, NR 183 No comparison1 HDCV, IM Not able to \ncalculate28/9 Minimal concerns\n1No comparison data available for this policy question available in these studies. \n2No comparison data available to calculate effect estimate.\n3Study quality for observational studies was assessed using the Newcastle Ottawa Scale.\nReminder: proposed changes\nHighlighted:  Proposed \nchanges to 2008 ACIP \nrecommendations \nRed box:   Today’s votes Primary \nimmunogenicity Long -term \nimmunogenicity \n#1 risk group\n(i.e., laboratorians) IM [0, 7 days] Titers every 6 months \nafter primary series\n#2 risk group\n(i.e., persons who \nhandle bats or enter \nhigh density bat \nenvironments)IM [0, 7 days] Titers every 2 years after \nprimary series\n#3 risk group (i.e., \nveterinarians, vet \nassistants, animal \nhandlers, vet students, \ntravelers etc.)IM [0, 7 days]Titer once at 2 years after \nprimary series\nOR\nBooster once no sooner \nthan day 21 and no later \nthan 3 yearsȽ", "summary": "National Center for Emerging and Zoonotic Infectious Diseases Summary of Evidence to Recommendations  Framework for Rabies Pre -Exposure Prophylaxis Vote Advisory Committee on Immunization Practices February 24, 2021Agam Rao, MD CAPT, US Public Health Service Poxvirus and Rabies Branch Centers for Disease Control and Prevention Rabies antibody response ▪Target response, i.e., ≥ minimum antibody titer, 0.5 IU/mL, regardless of  series –Children –Pregnant women –Persons ≥ 65 years of age…", "source_url": "https://www.cdc.gov/acip/evidence-to-recommendations/rabies-2-dose-etr.html", "pdf_url": "https://www.cdc.gov/acip/media/pdfs/2024/07/03-Rabies-Rao-508.pdf", "case": "acip", "sub_case": "other", "tags": ["acip", "cdc", "vaccines", "other"], "page_count": 35}
{"title": "01 Loehr influenza 508", "content": "National Center for Immunization & Respiratory Diseases\nInfluenza Work Group— Introduction\nDr. Jamie Loehr (Work Group Chair)\nAdvisory Committee on Immunization Practices\nApril 15, 2025\nInfluenza Work Group\nACIP Members\n•Jamie Loehr (Chair)\n•Robert Schechter\n•Albert Shaw\n•Keipp Talbot\nEx Officio\n•Timothy Brennan (FDA)\n•Uzo Chukwuma (IHS)\n•Walter Greenhalgh (HRSA)\n•Michael Ison (NIH)\n•Cynthia Nolletti (FDA)\n•Jo Resnick (FDA)\n•Chris Roberts (NIH)Liaison Representatives and \nConsultants\n•Robert Atmar\n•Kevin Ault\n•Ed Belongia\n•Hank Bernstein\n•Kris Bryant\n•Sarah Coles\n•Sandra Fryhofer\n•Robert Hopkins\n•Wendy Keitel\n•Camille Kotton\n•Krissy Moehling•Zackary Moore\n•Flor Munoz\n•Caitlin Newhouse\n•Jesse Papenburg\n•William Schaffner\n•Ken Schmader \n•Tamara Sheffield\n•Angela Sinilaite\n•Peter Szilagyi\n•Matthew Zahn\nCDC Lead\n•Lisa Grohskopf\n2\nCDC Participants\n•Lenee Blanton\n•Karen Broder\n•Alicia Budd\n•Kayla Calhoun\n•Jessie Chung\n•Jennifer DeCuir\n•Sascha Ellington\n•Tarayn Fairlie\n•Jill Ferdinands\n•Brendan Flannery\n•Andrew Kroger\n•Samantha Olson\n•David Shay\n•Tom Shimabukuro\n•Naomi Tepper\n3\nInfluenza Vaccine Composition for 2025 -26\n• On March 15, 2025, the U. S. Food and Drug Administration made recommendations for the \ncomposition of U.S. -licensed influenza vaccines for the 2025- 26 influenza season.\n• The 2025- 26 vaccine composition includes an update to the influenza A(H3N2 ) component.\n-For egg -based vaccines:\n›an A/Victoria/4897/2022 (H1N1)pdm09-like virus;\n›an A/Croatia/10136RV/2023 (H3N2) -like virus; and\n›a B/Austria/1359417/2021 (B/Victoria lineage) -like virus\n-For cell culture and recombinant vaccines:\n›an A/Wisconsin/67/2022 (H1N1)pdm09-like virus;\n›an A/District of Columbia/27/2023 (H3N2) -like virus; and\n›a B/Austria/1359417/2021 (B/Victoria lineage) -like virus\n4https://www.fda.gov/vaccines -blood -biologics/influenza -vaccine -composition -2025 -2026 -us-influenza- season\nInfluenza Vaccine Effectiveness (VE) Estimates\nUpdates:\n• Interim Estimates of 2024 –25 Seasonal Influenza Vaccine Effectiveness\n⁻Dr. Aaron Frutos (CDC/NCIRD/ID)\n• Interim Influenza Vaccine Effectiveness Against Laboratory -Confirmed Influenza , California , \nOctober 2024— January 2025\n⁻Dr. Sophie Zhu (California Department of Public Health and CDC/PHIC) and Dr. Joshua Quint  \n(California Department of Public Health)Issue:\n• Influenza vaccine effectiveness varies and is assessed annually through several CDC platforms \nfocusing on laboratory- confirmed influenza outpatient visits and hospitalizations in adult and \npediatric populations.\n• VE estimates are presented to the ACIP as they become available.\n• Preliminary 2024 -25  VE estimates are available from CDC platforms and from the California \nDepartment of Public Health.\n5\nFluMist (LAIV3) Self -/Caregiver Administration \nUpdates:\n•FluMist Self/Caregiver Administration \n⁻Dr. Allyn Bandell, AstraZenecaIssue:\n•On September 20, 2024, FDA approved FluMist for self or caregiver administration.\n•This program is expected to be available for the 2025 -26 influenza season.\n6\nUpcoming Votes\n7•Vote concerning updates to the 2025-26 ACIP influenza statement is \nexpected at the June 2025 ACIP meeting.\nFor more information, contact CDC\n1-800- CDC- INFO (232- 4636)\nTTY:  1 -888- 232- 6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.", "summary": "National Center for Immunization & Respiratory Diseases Influenza Work Group— Introduction Dr. Jamie Loehr (Work Group Chair) Advisory Committee on Immunization Practices April 15, 2025 Influenza Work Group ACIP Members •Jamie Loehr (Chair) •Robert Schechter •Albert Shaw •Keipp Talbot Ex Officio •Timothy Brennan (FDA) •Uzo Chukwuma (IHS) •Walter Greenhalgh (HRSA) •Michael Ison (NIH) •Cynthia Nolletti (FDA) •Jo Resnick (FDA) •Chris Roberts (NIH)Liaison Representatives and  Consultants •Robert…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/01-Loehr-influenza-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 8}
{"title": "02 Frutos influenza 508", "content": "Interim Estimates of 2024 –25 Seasonal Influenza \nVaccine Effectiveness\nAaron M. Frutos, PhD, MPH\nOn behalf of CDC Influenza Vaccine Effectiveness CollaboratorsNational Center for Immunization & Respiratory Diseases\n\nCDC Influenza Vaccine Effectiveness \nNetworks\nFour networks to evaluate vaccine effectiveness (VE) against laboratory -\nconfirmed influenza for children and adolescents and adults in the \noutpatient and inpatient settings \n•Investigating Respiratory Viruses in the Acutely Ill (IVY)\n•New Vaccine Surveillance Network (NVSN)\n•U.S. Flu Vaccine Effectiveness Network (US Flu VE)\n•Virtual SARS -CoV-2, Influenza, and Other respiratory viruses Network \n(VISION)CDC Influenza Vaccine Effectiveness Networks\n3\nVISION\nIVYNVSNThese networks include all ages across settings\nAgeSettingOutpatient \nclinic\nHospitalizationEmergency \ndepartment/ \nurgent careUS Flu VE\nAdults \n(≥18 years)Children and adolescents\n(6 months – 17 years)\n4\nNVSNNVSN: all settings\nAgeSettingOutpatient \nclinic\nHospitalizationEmergency \ndepartment/ \nurgent care\nAdults \n(≥18 years)Children and adolescents\n(6 months – 17 years)\n5\nNVSNUS Flu VE: Outpatient clinic and ED/UC\nUS Flu VE\nAgeSettingOutpatient \nclinic\nHospitalizationEmergency \ndepartment/ \nurgent care\nAdults \n(≥18 years)Children and adolescents\n(6 months – 17 years)\n6\nNVSNVISION: ED/UC & hospitalization\nUS Flu VE\nVISION\nAgeSettingOutpatient \nclinic\nHospitalizationEmergency \ndepartment/ \nurgent care\nAdults \n(≥18 years)Children and adolescents\n(6 months – 17 years)\n7\nIVYIVY: hospitalization\nAgeSettingOutpatient \nclinic\nHospitalizationEmergency \ndepartment/ \nurgent care\nAdults \n(≥18 years)Children and adolescents\n(6 months – 17 years)\n8\nIVYUS Flu VE: Outpatient clinic and ED/UC\nUS Flu VE\nAgeSettingOutpatient \nclinic\nHospitalizationEmergency \ndepartment/ \nurgent care\nAdults \n(≥18 years)Children and adolescents\n(6 months – 17 years)\n9\nIVYVISION: ED/UC & hospitalization\nUS Flu VE\nVISION\nAgeSettingOutpatient \nclinic\nHospitalizationEmergency \ndepartment/ \nurgent care\nAdults \n(≥18 years)Children and adolescents\n(6 months – 17 years)\n10\nThese networks include all ages across settings\nOutpatient\nVISION\nIVYNVSN\nAgeSettingOutpatient \nclinic\nHospitalizationEmergency \ndepartment/ \nurgent careUS Flu VE\nAdults \n(≥18 years)Children and adolescents\n(6 months – 17 years)\n11\nCDC influenza VE networks include patients from 23 \nstates\n12\n•Enrollees: Received medical care for an acute respiratory illness\n•Dates of enrollment: Fall 2024 – Early 2025\n•Design: Test-negative design\n–Comparing vaccination odds among case patients with influenza confirmed by \nmolecular assay versus control patients testing negative for influenza and SARS -CoV-2\n–Vaccination status: receipt of any 2024 –25 seasonal flu vaccine according to medical \nrecords, immunization registries, claims data, and/or self -report2024 –2025 Influenza VE Methods\n13\n•Analysis : VE = (1 – adjusted OR) x 100%\n–Adjusted for geographic region, age, calendar time of illness\n»US Flu VE, and VISION also adjusted for sex and race and ethnicity\n–VE estimates were calculated for influenza A subtypes A(H1N1)pdm09 and A(H3N2) \nwhen possible\n»Influenza A subtype estimates were not calculated for VISION because of \nlimited subtype data\n–VE was not estimated for some age groups and settings when sample size was small or \nwhen models did not converge2024 –2025 Influenza VE Methods\n14\nInfluenza A subtype by network\nInfluenza A subtype by network\nInfluenza A subtype by network, total (%)\nInfluenza A(H1N1)pdm09 Influenza A(H3N2)\nIVY 50 (31) 110 (69)\nNVSN 284 (52) 262 (48)\nUS Flu VE 168 (33) 337 (67)\n16\nPediatric VE\n(aged 6 months –17 years)\nPediatric VE against any influenza\nInfluenza test result by influenza vaccination \nstatus, no. vaccinated/Total (%)\nInfluenza -positive Influenza -negative VE (95% CI)\nNVSN (Outpatient) 100/482 (21) 855/2,487 (34) 59 (47 –68)\nUS Flu VE (Outpatient) 54/217 (25) 256/917 (28) 32 (1 –54)\nVISION (Outpatient) 1,322/9,563 (14) 5,943/27,356 (22) 60 (56 –63)\nNVSN (Inpatient) 28/119 (24) 613/1,523 (40) 63 (41 –76)\nVISION (Inpatient) 16/157 (10) 406/1,481 (27) 78 (60 –89)\n18\nPediatric VE against any influenza\n19\nPediatric VE against influenza A(H1N1)pdm09\n20\nPediatric VE against influenza A(H3N2)\n21\nAdult VE\n(aged ≥18 years)\nAdult VE against any influenza\nInfluenza test result by influenza vaccination \nstatus, no. vaccinated/Total (%)\nInfluenza -positive Influenza -negative VE (95% CI)\nUS Flu VE (Outpatient) 112/475 (24) 592/1,735 (34) 34 (16 –51)\nVISION (Outpatient) 5,631/26,011 (22) 25,842/76,628 (34) 54 (52 –56)\nIVY (Inpatient) 211/675 (31) 873/2,500 (35) 41 (28 –52)\nVISION (Inpatient) 905/2,959 (31) 10,869/28,074 (39) 55 (51 –59)\n23\nAdult VE against any influenza\n24\nAdult VE against influenza A(H1N1)pdm09\n25\nAdult VE against influenza A(H3N2)\n26\nAdult (aged ≥65) VE\nAdult (aged ≥65) VE against any influenza\nInfluenza test result by influenza vaccination \nstatus, no. vaccinated/Total (%)\nInfluenza -positive Influenza -negative VE (95% CI)\nUS Flu VE (Outpatient) 28/56 (50) 195/332 (59) 18 (-69–60)\nVISION (Outpatient) 2,575/5,731 (45) 14,978/27,525 (54) 51 (47 –54)\nIVY (Inpatient) 150/341 (44) 591/1,313 (45) 38 (19 –52)\nVISION (Inpatient) 693/1,897 (37) 8,903/19,271 (46) 57 (52 –61)\n28\nAdult (aged ≥65) VE against any influenza\n29\nDiscussion\n•Vaccination with a 2024 –25 influenza vaccine reduced the risk  for \nmedically attended influenza outpatient visits and hospitalizations  among \nchildren and adolescents and adults across 23 US states\n•Influenza v accination was effective against influenza A viruses  with \nvariation by subtype across networks\n•Interim Estimates of 2024 –2025 Seasonal Influenza Vaccine Effectiveness —\nFour Vaccine Effectiveness Networks, United States, October 2024 –\nFebruary 2025 | MMWRSummary of four CDC influenza VE networks\n31\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention.\nThank you\nAaron M. Frutos, PhD, MPH\nInfluenza Division\nNational Center for Immunization and Respiratory Diseases\nAFrutos@cdc.govWe’d like to thank our many collaborators \nfrom CDC, IVY , NVSN, US Flu VE, and \nVISION\nAdult (aged 18 –64) VE\nAdult (aged 18 –64) VE against any influenza\nInfluenza test result by influenza vaccination \nstatus, no. vaccinated/Total (%)\nInfluenza -positive Influenza -negative VE (95% CI)\nUS Flu VE (Outpatient) 84/419 (20) 397/1,403 (28) 37 (15 –53)\nVISION (Outpatient) 3,056/20,280 (15) 10,864/49,103 (22) 56 (53 –58)\nIVY (Inpatient) 61/334 (18) 282/1187 (24) 48 (28 –63)\nVISION (Inpatient) 212/1,062 (20) 1,966/8,803 (22) 51 (41 –59)\n34\nAdult (aged 18 –64) VE against any influenza\n35\nPediatric VE Tables\nPediatric VE against Influenza A(H1N1)pdm09\nInfluenza test result by influenza vaccination \nstatus, no. vaccinated/Total (%)\nInfluenza -positive Influenza -negative VE (95% CI)\nNVSN (Outpatient) 32/224 (14) 855/2,487 (34) 72 (59 –81)\nUS Flu VE (Outpatient) 9/50 (18) 256/917 (28) 53 (3 –79)\nNVSN (Inpatient) 13/60 (22) 613/1,523 (40) 63 (30 –81)\n37\nPediatric VE against Influenza A(H3N2)\nInfluenza test result by influenza vaccination \nstatus, no. vaccinated/Total (%)\nInfluenza -positive Influenza -negative VE (95% CI)\nNVSN (Outpatient) 62/218 (28) 855/2,487 (34) 42 (19 –58)\nUS Flu VE (Outpatient) 29/107 (27) 256/917 (28) 16 (-34–49)\nNVSN (Inpatient) 12/44 (27) 613/1,523 (40) 55 (14 –77)\n38\nAdult VE Tables\n(aged ≥18 years)\nAdult VE against Influenza A(H1N1)pdm09\nInfluenza test result by influenza vaccination \nstatus, no. vaccinated/Total (%)\nInfluenza -positive Influenza -negative VE (95% CI)\nUS Flu VE (Outpatient) 36/118 (31) 592/1,735 (34) 42 (8 –64)\nIVY (Inpatient) 12/50 (24) 873/2,500 (35) 39 (-14–67)\n40\nAdult VE against Influenza A(H3N2)\nInfluenza test result by influenza vaccination \nstatus, no. vaccinated/Total (%)\nInfluenza -positive Influenza -negative VE (95% CI)\nUS Flu VE (Outpatient) 56/230 (24) 592/1,735 (34) 25 (-6–48)\nIVY (Inpatient) 8/110 (26) 873/2,500 (35) 51 (22 –69)\n41", "summary": "Interim Estimates of 2024 –25 Seasonal Influenza  Vaccine Effectiveness Aaron M. Frutos, PhD, MPH On behalf of CDC Influenza Vaccine Effectiveness CollaboratorsNational Center for Immunization & Respiratory Diseases  CDC Influenza Vaccine Effectiveness  Networks Four networks to evaluate vaccine effectiveness (VE) against laboratory - confirmed influenza for children and adolescents and adults in the  outpatient and inpatient settings  •Investigating Respiratory Viruses in the Acutely Ill…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/02-Frutos-influenza-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 41}
{"title": "03 zhu influenza 508", "content": "Confidential -Low\nInterim Influenza Vaccine \nEffectiveness Against Laboratory -\nConfirmed Influenza, California, \nOctober 2024 –January 2025\nSophie Zhu, PhD and Joshua Quint, PhD\nCalifornia Department of Public Health\nAdvisory Committee on Immunization Practices Meeting\nApril 15, 2025\nConfidential -Low\nInfluenza VEData Type : \nElectronic records \nPatient interviewsData Sources : \nHospital networks\nPublic health surveillance\nPopulation :\nPediatric\nAdultSetting :\nInpatient\nOutpatient\nConsiderations for calculating vaccine effectiveness\nConfidential - Low\nInfluenza VEData Type : \nElectronic records \nPatient interviewsData Sources : \nHospital networks\nPublic health surveillance\nPopulation :\nPediatric\nAdultSetting :\nInpatient\nOutpatient\nConsiderations for calculating vaccine effectiveness\nConfidential - Low\n•January 1, 2023 \n•All vaccination records  must be \nreported to the California Immunization \nRegistry (CAIR) \n•Previously, only certain types of providers \nwere required to report\n•June 15,  2023: \n•All influenza test results  must be \nreported to California Reportable Disease \nInformation Exchange (CalREDIE)\n•Previously, only positive results were \nreported\nNew California Data Reporting Requirements\nConfidential - Low\n\nConfidential - Low\nPediatric : 6 mo–18 yrs\n2023–2024 CA estimates similar to  other VE platforms\nConfidential - Low\nMethods\nConfidential - Low\n•Dates: October 1, 2024 - January 31, 2025\n•Eligibility/inclusion criteria: California residents aged ≥6 months with a test result reported \nthrough the state electronic laboratory reporting (ELR) system\n•Outcome (test result): molecular (NAAT) or culture test results for influenza (A/B) \n•Exposure (vaccination status): documented dose of seasonal influenza vaccine at least 14 \ndays prior to test date\n•Exclusions: duplicate test results for persons with multiple records, laboratories with greater \nthan 50% weekly positive results\n•Analysis:  VE = (1 – adjusted OR) x 100%\n•Mixed -effects logistic regression model \n•Adjusted for continuous age (natural cubic spline), categorical race and ethnicity; testing \nweek and county as random effectsCase control study (unmatched)\nConfidential - Low\nNumber of positive influenza detections by laboratories\n2024 -2025 season to date\nFlu Type\nConfidential - Low\n•About 5% of influenza positive tests \nare subtyped, mostly from public \nhealth laboratories\n•Influenza A\n•53% A(H3) \n•43% A(H1)\n•4% A not subtyped\n•Only ~300 influenza B samples \nlineage typed this season\n•Persons with severe disease may be \nmore likely to have results subtyped\nInfluenza subtyping\nConfidential - Low\nTotal \nN = 591,321\nInfluenza Positive\n22.8%\nVaccinated\n17.6%Not Vaccinated\n82.4%Influenza Negative\n77.2%\nVaccinated\n25.9%Not Vaccinated\n74.1%Study Population\nTest Positivity and Vaccination Status\nConfidential - Low\nTest Negative Test Positive\nTotal No. 456,437 134,884 \nMedian Age\n       25th percentile\n       75th percentile43 yrs \n20 yrs\n67 yrs30 yrs\n11 yrs\n55 yrs\nEthnicity - Hispanic or Latino 24% 29%\nRace\nWhite\nUnknown\nOther\nAsian\nBlack\nNHPI, AI/AN, or Multiple46%\n20%\n19%\n8%\n6%\n<1%*39%\n22%\n23%\n8%\n6%\n<1%*\nNHPI = Native Hawaiian or Pacific Islander; AI/AN = American Indian or Alaska Native; * <1% each Study Population\nDemographics\nConfidential - Low\n•Age group by Type (A/B)\n•Influenza A subtype (H1N1/H3N2)\n•Mode of administration (LAIV/non -LAIV)\n•Weekly cumulative\n•Month -specific by Type (A/B)Vaccine effectiveness estimates\nConfidential - Low\n43.7 45.6Vaccine effectiveness by age group\nCalifornia 2024 –2025\nVE (%)\nConfidential - Low\nVE (%)\nVaccine effectiveness by type and age group\nCalifornia 2024 –2025\nConfidential - Low\nVaccine effectiveness by influenza A subtype\nCalifornia 2024 –2025\n\nConfidential - Low\nYear Vaccine Type VE (95% CI) Count Median Age (IQR)\n2024 LAIV 61 (51, 69) 455 7.3 (4.9 –10.4)\n2024 Not LAIV 48 (46, 50) 21,980 7.8 (4.4 –12.4)\n2023 LAIV 45 (35, 54) 1,387 7.9 (5.3 –10.9)\n2023 Not LAIV 52 (51, 54) 66,088 7.3 (4.2 –11.9)Live Attenuated Influenza Vaccine (LAIV) \nestimates among children ages 2 –17\nConfidential - Low\nPositive \nTest \nResults\nVE (%)Cumulative Influenza vaccine effectiveness\nCalifornia 2024 –2025\nConfidential - Low\nOctober November December JanuaryVE (%)Vaccine effectiveness by month  of influenza test\nCalifornia 2024 –2025\nConfidential - Low\nOctober November December JanuaryVaccine effectiveness by month  and type\nCalifornia 2024 –2025VE (%)\nConfidential - Low\nLimitations\n1.Incomplete documentation and reporting of vaccination and testing\n2.Inability to assess partial/full vaccination status for children aged <9 years\n3.Lack of symptom information, test setting, and outcome status (illness, \nhospitalization, or death)\n4.Incomplete and potentially biased reporting for influenza subtypes\n5.Lack of control for other confounders (health seeking behavior, pre -existing \nconditions)\nConfidential - Low\nSummary\n1.Current seasonal influenza vaccines provide protection against \nlaboratory -confirmed influenza for persons aged ≥6 months\n•Higher VE for influenza B & younger age groups (<18 years, 18 -49 years)\n2.Expanded and improved public health data can be leveraged to \ncalculate timely in -season influenza effectiveness\n•Useful to promote additional prevention measures prior to peak\n•Prepare for increased hospital capacity\nConfidential - Low\nAcknowledgements\nCalifornia Local Health Departments\nCDPH Division of Communicable \nDisease Control\n•Tomás León\n•Monica Sun\n•Nancy J. Li\n•Cynthia Yen\n•Cora Hoover\n•Robert Schechter\n•Seema Jain\n•Erin L. MurrayNCIRD Influenza Division\n•Brendan Flannery\n•Mark Tenforde\n•Sascha Ellington\n•Jessie Chung", "summary": "Confidential -Low Interim Influenza Vaccine  Effectiveness Against Laboratory - Confirmed Influenza, California,  October 2024 –January 2025 Sophie Zhu, PhD and Joshua Quint, PhD California Department of Public Health Advisory Committee on Immunization Practices Meeting April 15, 2025 Confidential -Low Influenza VEData Type :  Electronic records  Patient interviewsData Sources :  Hospital networks Public health surveillance Population : Pediatric AdultSetting : Inpatient Outpatient…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/03-zhu-influenza-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 23}
{"title": "04 bandell influenza 508", "content": "4/11/2025\n1\n1\n2\n4/11/2025\n2\n3\n4\n4/11/2025\n3\n5\n6\n4/11/2025\n4\n7\n8\n4/11/2025\n5\nCO-9Instructions for Use Based on Human Factors Usability Studies \nthat Aligned with FDA Guidance1\n1. Application of Human Factors Engineering Principles for Combination Products: Questions and Answers, Guidance for Industry and FDA Staff, 2023ObjectiveConfirm intended users can administer FluMist to themselves or to an \nappropriate child without errors or difficulties that could result in \nadministration failure Confirm intended users can administer FluMist to themselves or to an \nappropriate child without errors or difficulties that could result in \nadministration failure \nIntended \nUsersAdult patients aged 18 to 49 years (self-administered) \nAdult caregivers (≥18 years) who administer to adults or children \n(2-17 years)Adult patients aged 18 to 49 years (self-administered) \nAdult caregivers (≥18 years) who administer to adults or children \n(2-17 years)\nStudy \nRecruitmentIntended to reflect mix of male/female participants, race, \neducational background, right/left handedness, with or without nasal \nspray experienceIntended to reflect mix of male/female participants, race, \neducational background, right/left handedness, with or without nasal \nspray experience\n9\n10\n4/11/2025\n6\n11\n12\n4/11/2025\n7\n13\n14\n4/11/2025\n8\n15\n16\n4/11/2025\n9\nCO-18\nPatients Answer Yes/No Questions Aligned with Flu ACIP \nRecommendations Allowing Pharmacists to Determine Eligibility \nwomen.17\n18\n4/11/2025\n10\nCO-19\nPatients Answer Yes/No Questions Aligned with Flu ACIP \nRecommendations Allowing Pharmacists to Determine Eligibility \nwomen.women.\nCO-20Patients Answer Yes/No Questions Aligned with Flu ACIP \nRecommendations Allowing Pharmacists to Determine Eligibility \nwomen.19\n20\n4/11/2025\n11\n21\n22\n4/11/2025\n12\n23\n24\n4/11/2025\n13\n25\n26\n4/11/2025\n14\n27\n28\n4/11/2025\n15\n29\n30\n4/11/2025\n16\n31\n32\n4/11/2025\n17\nCO-34\nGlobal Vaccine Effectiveness of IIV and LAIV4 in Pediatric Patients –\nCompilation from Non-Comparative Studies (2019-2024)\n020406080100\n65\n(41, 79)59\n(48, 67)67\n(48, 80)VE, % (95% CI) \nDATA ARE UNAVAILABLE FOR 20/212019/20 2021/22 2022/23 2023/24\n2 years 2–6 years45\n(13, 66)\n49\n(25, 66)48\n(8, 70)66\n(58, 72)\n52\n(37, 64)34\n(19, 46)40\n(22, 53)64\n(51, 74)\n13\n(–70, 55)\n51\n(36, 63)72\n(50, 85)\n51\n(19, 70)34\n(–7, 59)64\n(49, 75)77\n(62, 86)\n71\n(31, 90)\n72\n(24, 89)\n2–17 years 2–6 years\n6 mo–17 years60\n(57, 64)\nUK1\nn=N/A\n2–17\nyearsFIN2\nn=195FIN2\nn=178FIN2\nn=1149FIN2\nn=1102US3,4†\nn=646\n6 mo–\n8 yearsUS3,4†\nn=471\n9–17\nyearsDEN5‡\nn=473FIN6§\nn=349UK7\nn=N/A\n1–17\nyearsUS8,9†ۅ\nn=117\n9–17 yearsFIN6§\nn=299US8,9†ۅ\nn=95\n6 mo–\n8 yearsUK10\nn=N/ADEN11‡\nn=339\n2–6 yearsUS12†‡\nn=34\n1–17\nyearsUK10\nn=N/AUK13\nRCGP, \nCARI\nn=N/A\n2–17\nyearsUS14,15†\nNVSN\nn=622US14,15†\nUS Flu VE\nn=283US14,15†\nVISION\nn=6068LAIV IIV\nData for FLUMIST Quadrivalent (LAIV4) are relevant to FLUMIST because both vaccines are \nmanufactured using the same process and have overlapping compositions17\nVE CIs truncated at 0 to enable graphical display. †Data for all vaccines, but little use of LAIV4 or IIV3 in the US.4,9,15,16 ‡Data for interim influenza A only. §End-of-season estimates from Week 40 (2021) to Week 26 (2022). ‖A(H3N2) represented an estimated 94% of all influenza-positive participants.\nCI = confidence interval; DEN = Denmark; FIN = Finland;GB-PC = Great Britain Primary Care; IIV = inactivated influenza vaccine; IIV3 = trivalent inactivated influenza vaccine; LAIV = live attenuated influenza vaccine; LAIV4 = quadrivalent live attenuated influenza vaccine; \nmo = months; n = total number of cases; N/A = not available; NVSN = New Vaccine Surveillance Network; UK = United Kingdom; US = United States; VE = vaccine effectiveness; VISION = Virtual SARS-CoV-2, Influenza, and Other respiratory viruses Network.\n1. Public Health England. Surveillance of influenza and other respiratory viruses in the UK. Winter 2019 to 2020; 2. In-house data, AstraZeneca. DoF 143691; 3. TenfordeMW et al. Article and supplementary appendix. Clin Infect Dis . 2021;73(11):e4244–e4250; 4. Committee on Infectious Diseases. Pediatrics . \n2019;144(4):e20192478; 5. EmborgH et al. Euro Surveill . 2022;27(15):2200278;6. In-house data, AstraZeneca. DoF 168928; 7. UK Health Security Agency. Surveillance of influenza and other seasonal respiratory viruses in winter 2021 to 2022; 8. Price AM et al. Clin Infect Dis. 2023;76(8):1358–1363; 9. Grohskopf LA et \nal. MMWR RecommRep. 2021;70(5):1–28; 10. UK Health Security Agency. Surveillance of influenza and other seasonal respiratory viruses in the UK, winter 2022 to 2023; 11. Kissling E et al. Euro Surveill. 2023;28(21):2300116; 12. McLean HQ et al. MMWR RecommRep. 2023;72(8):201–205; 13. UK Health Security \nAgency. Surveillance of influenza and other seasonal respiratory viruses in the UK, winter 2023 to 2024; 14. Frutos AM et al. MMWR MorbMortal WklyRep . 2024;73(8):168–174; 15. Grohskopf LA, et al. MMWR RecommRep . 2023;72(2):1–25; 16. Centersfor Disease Control and Prevention. Live Attenuated Influenza \nVaccine [LAIV] (The Nasal Spray Flu Vaccine); 17. FLUMIST Prescribing Information. August 2024.33\n34", "summary": "4/11/2025 1 1 2 4/11/2025 2 3 4 4/11/2025 3 5 6 4/11/2025 4 7 8 4/11/2025 5 CO-9Instructions for Use Based on Human Factors Usability Studies  that Aligned with FDA Guidance1 1. Application of Human Factors Engineering Principles for Combination Products: Questions and Answers, Guidance for Industry and FDA Staff, 2023ObjectiveConfirm intended users can administer FluMist to themselves or to an  appropriate child without errors or difficulties that could result in  administration failure…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/04-bandell-influenza-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 17}
{"title": "01 Schechter COVID 508", "content": "ACIP COVID -19 Vaccines Work Group\nRobert Schechter, MD, MSc\nCOVID -19 ACIP Work Group Chair\nAdvisory Committee on Immunization Practices Meeting\nApril 15, 2025National Center for Immunization and Respiratory Diseases\n\n•In August 2024, the Food and Drug Administration authorized \nand approved: ​\n-Moderna COVID -19 vaccine* in persons ≥6 months ​\n-Novavax COVID -19 vaccine** in persons ≥12 years\n-Pfizer -BioNTech COVID -19 vaccine* in persons ≥6 months ​2024 –2025 COVID -19 vaccines\n*Omicron JN.1 lineage, KP.2 strain\n**Omicron JN.1 lineage, JN.1 strain\n•Everyone aged ≥6 months should receive 2024 –2025 COVID -19 vaccination\n-Children aged 6 months –4 years need multiple doses of COVID -19 vaccines to be up to date, \nincluding at least 1 dose of 2024 –2025 COVID -19 vaccine\n-People aged 5 -64 years should get 1 dose1 of 2024 -2025 COVID -19 vaccine\n-People who are ≥65 years2 and people ≥6 months of age with moderate or severe \nimmunocompromise3 should receive  a second dose  of 2024 –2025 COVID -19 vaccine 6 \nmonths after their first  2024 –2025  dose (minimum interval of 2 months)\n-People  with moderate  or severe  immunocompromise  may receive additional doses of \n2024 –2025 COVID -19 vaccines under shared clinical decision -making (minimum interval of 2 \nmonths)2024 –2025 COVID -19 vaccine recommendations \n1. People who are unvaccinated and receive Novavax COVID -19 vaccine for initial vaccination should receive 2 doses of 2024 –2025 Novavax COVID -19 vaccine\n2. People who are unvaccinated and receive Novavax COVID -19 vaccine for initial vaccination should receive 2 doses of 2024 –2025 Nov avax COVID -19 vaccine \nfollowed by a third dose of any 2024 –2025 COVID -19 vaccine dose 6 months (minimum interval 2 months) after the second dose.\n3. If previously unvaccinated or receiving initial vaccination series, at least 2 doses of 2024 –2025 vaccine are recommended, an d depending on vaccination history \nmore may be needed. This additional 2024 –2025 vaccine dose is recommended 6 months (minimum interval 2 months) after completion of initial vaccination series.​\nProvisional Weekly COVID -19 Deaths in the United States \nReported to CDC, by Week October 2021 –March  2025\nhttps://covid.cdc.gov/covid -data -tracker/#trends_weeklydeaths_select_00  \nAccessed April 4, 202505,00010,00015,00020,00025,000\nOctober November December January February March April May June July August SeptemberWeekly Deaths\nSurveillance Month2021-2022 2022-2023 2023-2024 2024-2025\nWeekly rates of COVID -19 associated hospitalizations \nby season – COVID -NET\nhttps://www.cdc.gov/covid/php/covid -net/index.html\nAccessed April 4 , 2025\n\nPreliminary Estimates of Disease Burden, \nOctober 1, 2024 through March  22, 2025\nDisease Illnesses Outpatient \nVisitsHospitalizations Deaths\nCOVID -191 7.7 – 13.5 \nMillion1.9 – 3.2 \nMillion220,000 – \n370,00026,000 – \n43,000\nInfluenza2 44 – 76 \nMillion20 – 34 \nMillion580,000 – 1.2 \nMillion25,000 – \n120,000\n1 https://www.cdc.gov/covid/php/surveillance/burden -estimates.html\n2 https://www.cdc.gov/flu -burden/php/data -vis/2024 -2025.html  \nAccessed April 4, 2025\nCurrent season week ending date refers to the 2024 -2025 season only. For the 2023 -2024 season, the corresponding week is represe nted.\n2024 -2025 vaccines were available starting August 22, 2024. 2023 -2024 vaccines were available starting September 12, 2023.\nhttps://www.cdc.gov/covidvaxview/weekly -dashboard/adult -vaccination -coverage.html    \nAccessed April 4, 2025 COVID -19 vaccination coverage among adults 18 years \nand older, 2023 –2024 through 2024 –2025\n\nACIP COVID -19 Work Group Meeting Review\nNovember 2024 – April 2025\n•Considerations for a risk -based and universal vaccine recommendation for the \n2025 –2026 COVID -19 vaccines\n•COVID -NET data for those with and \nwithout risk factors\n•COVID -19 mortality\n•COVID -19 vaccine hesitancy and \nuptake\n•COVID -19 vaccine safety and \neffectiveness•Moderna mRNA -1283 COVID -19 \nvaccine  candidate\n•Seroprevalence of SARS -CoV-2\n•Post -COVID conditions (Long COVID)\n•Multisystem Inflammatory Syndrome \nin Children (MIS -C)\n•Feedback from liaison organizations\n Introduction  Dr. Robert Schechter (ACIP, WG Chair)\nModerna mRNA -1283 COVID -19 \nvaccine candidateDr. Bishoy Rizkalla\nEpidemiology and risk factors for \nCOVID -19 hospitalizationsDr. Fiona Havers\nVaccine effectiveness update Dr. Ruth Link -Gelles\nWork Group Considerations for use \nof 2025 –2026 COVID -19 vaccinesDr. Lakshmi PanagiotakopoulosAgenda: April 15, 2025\n•Today’s meeting:  Update on ongoing review of considerations \nfor use of 2025 –2026 COVID -19 vaccines\n•Spring : Anticipated FDA Vaccines and Related Biological \nProducts Advisory Committee (VRBPAC) meeting to discuss and \nmake recommendations on strain selection for 2025 –2026 \nCOVID -19 vaccines\n•June ACIP meeting : Discussion and vote on recommended use \nof the 2025 –2026 vaccine\n•Late summer/early fall : Anticipated 2025 –2026 COVID -19 \nvaccine availabilityPreliminary Timeline, 2025 –2026 COVID -19 \nVaccines \nWork Group members\nACIP members\n•Robert Schechter  (chair)\n•Noel Brewer\n•Oliver Brooks\n•George Kuchel\n•Keipp  Talbot\nEx-officio/government members\n•BARDA: Christine Oshansky\n•CDC: Alan Lam\n•FDA: Adam Spanier, Rachel Zhang\n•IHS: Uzo Chukwuma\n•NIH: Chris Roberts\nCDC co -Leads\n•Lakshmi Panagiotakopoulos\n•Lauren RoperLiaisons\n•AAFP: Jonathan Temte\n•AAP: Sean O’Leary\n•ACOG: Naima Joseph, \nLaura Riley (alternate)\n•ACP: Jason Goldman\n•AGS: Ken Schmader\n•AIM: Heather Roth\n•AMA: Sandra Fryhofer\n•ANA: Ruth Francis \n•APhA : Richard Dang\n•ASTHO: Marcus Plescia\n•CSTE: Paul Cieslak ,            \nChristine Hahn\n•IDSA: James McAuley \n•NACCHO: Matt ZahnLiaisons, cont’d\n•NACI: Eva Wong, Matthew \nTunis (alternate)  \n•NFID: Robert Hopkins, Bill \nSchaffner (alternate) \n•SHEA: Preeti Mehrotra, \nMarci Drees (alternate)\nConsultants\n•Ed Belongia  \n•Hank Bernstein  \n•Matthew Daley\n•Lisa Jackson\n•Jennifer Nelson\n•Stanley Perlman\n•Peter Szilagyi\nCDC participants \n•Amadea Britton\n•Mary Chamberland\n•Fatimah Dawood\n•Nicole Dowling\n•Jonathan Duffy\n•Kristen Folsom\n•Molly Gaines -McCollom\n•Julianne Gee\n•Monica Godfrey\n•Susan Goldstein\n•Lisa Grohskopf\n•Demorah Hayes\n•Suzanne Heitfeld•Michele Hlavsa\n•Jefferson Jones\n•Ruth Link -Gelles\n•Jessica MacNeil\n•Josephine Mak\n•Seth Abram Meador\n•Michael Melgar\n•Sarah Meyer\n•Noelle -Angelique Molinari\n•Danielle Moulia\n•Ismael Ortega -Sanchez\n•Manisha Patel\n•Pragna Patel•Amanda Payne\n•Jamison Pike\n•Hannah Rosenblum\n•Sierra Scarbrough\n•John Su\n•Diya Surie\n•Natalie Thornburg\n•Melinda Wharton\n•Trang Wisard\n•JoEllen Wolicki\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the U.S. Centers for Disease Control and Prevention.", "summary": "ACIP COVID -19 Vaccines Work Group Robert Schechter, MD, MSc COVID -19 ACIP Work Group Chair Advisory Committee on Immunization Practices Meeting April 15, 2025National Center for Immunization and Respiratory Diseases  •In August 2024, the Food and Drug Administration authorized  and approved: ​ -Moderna COVID -19 vaccine* in persons ≥6 months ​ -Novavax COVID -19 vaccine** in persons ≥12 years -Pfizer -BioNTech COVID -19 vaccine* in persons ≥6 months ​2024 –2025 COVID -19 vaccines *Omicron…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/01-Schechter-COVID-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 13}
{"title": "02 Rizkalla COVID 508", "content": "Overview  of Moderna’s  Investigational  \nNext  Generation  COVID -19 Vaccine, \nmRNA -1283,  in Individuals  ≥12 Years  of Age\n© 2025  Moderna,  inc. All rights  reserved.ACIP\nBishoy  Rizkalla,  PhD \nApril  15, 20251\n2\nCOVID -19 Remains  a Leading  Cause  of Hospitalization \namong  Respiratory  Viruses  in the US\nAdults  ≥65 years  account  for:\n•>60%  of COVID -19 hospitalizations\n(since  2023 )2\n•~76%  of deaths  (since  2020)3•95% of adults  hospitalized  with \nCOVID -19 have  ≥1 underlying  \nmedical  conditionRisk Factors  for Severe  COVID  Infection  in the US1\nAdvancing  Age Pre-Existing  Chronic  Conditions4\n© 2025  Moderna,  inc. All rights  reserved.Effective  prophylactic  approaches  to address  the burden \nof disease  in vulnerable  populations  remain  a high  priority\n1.https:// www.cdc.gov/covid/hcp/clinical -care/underlying -conditions.html\n2.https://covid.cdc.gov/covid -data -tracker/#covidnet -hospitalization -network\n3.https://covid.cdc.gov/covid -data -tracker/#demographics\n4.https:// www.cdc.gov/pcd/issues/2021/21_0123.htm\n3\nDesign  of mRNA -1283\nInvestigational  Next  Generation  COVID -19 Vaccine\n7-amino  acid  flexible  linker\nN-terminal \nDomain \n(NTD)Receptor \nBinding \nDomain \n(RBD)\nLower  mRNA  dose  (10 µg; 1/5th of dose  of Spikevax)\n© 2025  Moderna,  inc. All rights  reserved.1.Piccoli  et al, Cell 2020  doi: 10.1016/j.cell.2020.09.037\n2.Dejnirattisai  et al, Cell 2021  doi: 10.1016/j.cell.2021.03.055\n3.Cerutti  et al, Cell Host Microbe  2021  doi: 10.1016/j.chom.2021.03.005\nPivotal  Safety,  Immunogenicity \nand Relative  Vaccine  Efficacy \nStudy\n© 2025  Moderna,  inc. All rights  reserved.Study  3014\nChalkias  et al. Lancet  ID, in press,  2025\n5\nStudy  Design  & Primary  Objectives\nRandomized,  blinded,  active -controlled  phase  3 trial\nParticipants  ≥12 years\nmRNA -1283  (10 µg)\nOriginal:  Omicron  BA.4/BA.5 \nBivalent  Vaccine\nSPIKEVAX  (mRNA -1273  - 50 µg)\nOriginal:  Omicron  BA.4/BA.5 \nBivalent  VaccineStratified \nrandomization:\nAge groups \n(12-17, 18-64, and\n≥65)N = 5,728\nN = 5,7261:1\nPrimary  Objectives\nSafety  and \nReactogenicity\nmRNA -1283  & SPIKEVAXNon-Inferior \nImmunogenicity \nmRNA -1283  vs SPIKEVAXNon-Inferior  Relative \nVaccine  Efficacy  (rVE) \nmRNA -1283  vs SPIKEVAX\n(based  on CDC  COVID -19 definition)\n© 2025  Moderna,  inc. All rights  reserved.\n6\n© 2025  Moderna,  inc. All rights  reserved.Demographics  and Baseline  Characteristics  Balanced \nBetween  Groups\nStudy  301 - Safety  SetmRNA -1283  (10 µg)\nN = 5706SPIKEVAX  (50 µg)\nN = 5711\nMean  age,  years  (range) 51.1 (12, 96) 51.2 (12, 90)\nMedian  age,  years 56 55\nAge subgroup,  % (n)\n12-17 years 8.7%  (497) 8.7%  (495)\n18-64 years 62.7%  (3575) 62.6%  (3576)\n≥65 years 28.6%  (1634) 28.7%  (1640)\nRace/Ethnicity,  % (n)\nWhite 81.8%  (4670) 82.5%  (4711)\nBlack  or African  American 11.2%  (640) 11.1%  (635)\nAsian 3.9%  (225) 3.2%  (183)\nHispanic  or Latino 13.5%  (769) 13.0%  (741)\n≥1 pre-existing  COVID -19 comorbidity  (CDC  definition) 46.0%  (2626) 46.6%  (2664)\nRace/ethnicity  generally  representative  of US population\nhttps:// www.cdc.gov/covid/risk -factors/index.html;;  https:// www.census.gov/quickfacts/fact/table/US/RHI225223\n7Prior SARS -CoV-2 Infection  and Time  Since  Last COVID -19 \nVaccination  Balanced  Between  Groups\nStudy  301 - Safety  Set\n•Eligibility  criteria:\n•All study  participants  previously  received  primary  series  of COVID -19 vaccine\n•Adults  ≥18 years  received  ≥1 dose  beyond  primary  series\nmRNA -1283  (10 µg)\nN = 5706\n© 2025  Moderna,  inc. All rights  reserved.SPIKEVAX  (50 µg)\nN = 5711\nPrior SARS -CoV -2 Infection1 73.8% 74.8%\nMonths  since  last COVID -19 vaccination, \nmedian  (Q1, Q3)9.8 (7.6, 16.9) 9.8 (7.7, 16.7)\n1.Evidence  of SARS -CoV -2 infection  pre-study  vaccination  (defined  by a positive  RT-PCR test, and/or  a positive  serology  test based \non binding  antibody  specific  to SARS -CoV -2 nucleocapsid)\n2.Q - quartile\nSafety  Results\n© 2025  Moderna,  inc. All rights  reserved.Study  3018\n9\nPrimary  Safety  Endpoints  and Duration  of Follow -up\nStudy  301 Safety  Set – Median  8.8 Months  Follow -up\nActive  Safety \nSurveillanceSolicited  Local  and \nSystemic  Adverse \nReactions\nUnsolicited  Adverse  Events\nMedically  Attended  AEs, Serious  AEs Including  Death,  AEs Leading  to Discontinuations\nAdverse  Events  of Special  Interest\n(including  Myocarditis,  Pericarditis,  Thrombocytopenia,  Neurologic  Events1, and Anaphylaxis)\n7 Days  28 Days  12 months\n© 2025  Moderna,  inc. All rights  reserved.Trial overseen  by independent  Data  and Safety  Monitoring  Board  (DSMB)\n1. Neurologic  events  of interest  include  Guillain -Barre  syndrome,  acute  disseminated  encephalomyelitis,  Bell’s  palsy, and  seizures;  2. AE  – adverse event\n10\nSolicited  Local  Adverse  Reactions  within  7 Days  of Vaccination \nwith mRNA -1283  and SPIKEVAX\nStudy  301 – Solicited  Safety  Set\n69%78%\n2%4% 4%6%20% 18%\n0%20%60%\n40%80%100%\nmRNA -\n1283mRNA -\n1273mRNA -\n1283mRNA -\n1273mRNA -\n1283mRNA -\n1273mRNA -\n1283mRNA -\n1273Pain Erythema  Swelling  Axillary  Swelling\nor Tenderness\n1283 SPIKEVAX 1283 SPIKEVAX 1283 SPIKEVAX 1283 SPIKEVAX\nGrade  3\nGrade  2\nGrade  1\n© 2025  Moderna,  inc. All rights  reserved.•Pain  at the injection  site was most  frequently  observed  solicited  local  adverse  reaction  for both  groups\n•1 – 2 days  median  duration  for local  adverse  reactions\nFeb 23, 2024  data  cutoff;  mRNA -1283,  N = 5702;  mRNA -1273,  N = 5706;  no grade  4 reactions\n11\nSolicited  Systemic  Adverse  Reactions  within  7 Days  of Vaccination \nwith mRNA -1283  and SPIKEVAX\nStudy  301 – Solicited  Safety  Set\n6% 5%44%41%50% 49%\n38% 37%\n30%28%\n12% 11%23%20%\n20%40%60%80%100%Nausea/ \nVomitingFever  Headache  Fatigue Arthralgia Chills\n0%\n1283  SPIKEVAX  1283  SPIKEVAX  1283  SPIKEVAX  1283  SPIKEVAX  1283  SPIKEVAX  1283  SPIKEVAX  1283  SPIKEVAX\nMyalgia\nGrade  3\nGrade  2\nGrade  1\n•Fatigue,  headache,  and myalgia  most  frequently  observed  solicited  systemic  adverse  reactions  for both  groups\n•1-2 days  median  duration  for systemic  adverse  reactions\n© 2025  Moderna,  inc. All rights  reserved.Feb 23, 2024  data  cutoff;  mRNA -1283,  N = 5702;  mRNA -1273,  N = 5706.  One participant  in the mRNA -1273  group  had a grade 4  fever.  No grade 4 reactions.\n12\n© 2025  Moderna,  inc. All rights  reserved.Similar  Frequency  of Unsolicited  AEs Within  28 Days  After  Injection, \nRegardless  of Relationship  to Vaccine,  Between  mRNA -1283  and SPIKEVAX\nStudy  301 – Safety  Set\nmRNA -1283  (10 µg)\nN = 5706SPIKEVAX  (50 µg)\nN = 5711\nAll, % (n) 12% (701) 12% (680)\nSerious 0.2%  (13) 0.3%  (18)\nFatal 0% (0) 0.02%  (1)\nMedically -Attended 7% (425) 7% (422)\nLeading  to Study  Discontinuation 0% (0) 0.02%  (1)\nAny Adverse  Event  of Special  Interest (AESI) 0.05%  (3) 0.1%  (6)\nMyocarditis/Pericarditis 0% (0) 0% (0)\nFeb 23, 2024  data  cutoff\nSafety  Summary  through  Median  8.8 Months  of Follow -up\n© 2025  Moderna,  inc. All rights  reserved.•No imbalances  in any adverse  events  between  the vaccine  groups\n•No myocarditis  or pericarditis  in recipients  of mRNA -1283\n•No safety  concerns  identified13\nImmunogenicity\n© 2025  Moderna,  inc. All rights  reserved.Study  30114\n15mRNA -1283  Elicited  Higher  Antibody  Response  at Day 29 \nCompared  to SPIKEVAX\nStudy  301 – Per-Protocol  Immunogenicity  Set (Randomly  Selected  Subset)\n0 1 2GMC  (95%  CI)1mRNA -1283\n(10 µg)\nN = 621SPIKEVAX\n(50 µg)\nN = 568GMR  (95%  CI)\nof mRNA -1283  over  SPIKEVAX\nOriginal  SARS -CoV-210632\n(9960,  11349)8577\n(8013,  9180)1.2 (1.1, 1.4)\n1.3 (1.2, 1.5)\nBA.4/BA.52341\n(2167,  2529)1754\n(1618,  1901)\n0.667\n20 25Seroresponse  Rate,  % (95% CI) Seroresponse  Rate  Difference  (95%  CI)\nOriginal  SARS -CoV-283.6% 72.9% 10.7%  (6.0, 15.4)\n(80.4,  86.4) (69.0,  76.5)\nBA.4/BA.579.9% 65.5% 14.4%  (9.3, 19.4\n(76.5,  83.0) (61.4,  69.4))\n-25 -20 -15 -10 -5 0 5 10 15\n•GMR:  Lower  95% CI of GMR  was >0.667\n•Seroresponse  rate difference:  Lower  95% CI of difference  >–10%\n© 2025  Moderna,  inc. All rights  reserved.Noninferiority \nSuccess  Criteria  Met\nSeroresponse  rate defined  as antibody  value  change  from  baseline  below  lower  limit of quantification  (LLOQ)  to ≥4 × LLOQ,  or ≥4-fold rise if baseline  ≥ LLOQ  and <4 × LLOQ, \nor ≥2-fold rise if baseline  is ≥4 × LLOQ;  GMC – geometric  mean  concentration;  GMR  – geometric  mean  ratio\n1. GMC  estimated  based  on ANCOVA model\n16\nHighest  BA.4/BA.5  Neutralizing  Antibody  Geometric  Mean  Ratio \n(GMR)  at Day 29 in Adults  ≥65 Years  Old\nStudy  301 – Per Protocol  Immunogenicity  (Randomly  Selected  Subset)\n≥ 65 Years\n3732340\n2971327\nD1 D29\nN = 152D1 D29\nN = 1593252121\n3191661\nD1 D29\nN = 378D1 D29\nN = 3164793561\n5933399\n101001000\nD1 D29 D1 D291.8 (1.4, 2.2) 1.3 (1.1, 1.5)SPIKEVAX  (50 µg)\n18-64 Years\nN = 91 N = 93GMC1\n(95%  CI)mRNA -1283  (10 µg)\n12-17 Years\nGMR  (95%  CI) = 1.0 (0.8, 1.3)\n10000\n1. GMC  estimated  based  on ANCOVA  model\n© 2025  Moderna,  inc. All rights  reserved.\n17\nmRNA -1283  Elicited  Consistently  Higher  Antibody  Responses \nCompared  to SPIKEVAX  Over  Time  - Adults  ≥65 Years  of Age\nD29 D29 D29 D29 D29 D29Day 29 Day 91 Day 181\nGMR  (95%  CI) = 1.8 (1.4, 2.2) 1.8 (1.5, 2.3) 1.7 (1.3, 2.2)\n10000\n2340GMC1 1566\nAgainst  1327  1086\nOmicron  863\nBA.4  / BA.5  1000  634\n(95%  CI)\n100\nmRNA -1283  SPIKEVAX  mRNA -1283  SPIKEVAX  mRNA -1283  SPIKEVAX\n(10 µg) (50 µg) (10 µg) (50 µg) (10 µg) (50 µg)\nN = 152 N = 159 N = 149 N = 155 N = 122 N = 1421086\n634\nD29 D29 mRNA -1283\n(10 µg)\nN = 122SPIKEVAX\n(50 µg)\nN = 1421566\n863\nD29 D29 mRNA -1283\n(10 µg)\nN = 149SPIKEVAX\n(50 µg)\nN = 155GMC1\nAgainst \nOmicron \nBA.4  / BA.5 \n(95%  CI)1327\n1001000\nD29 D29 mRNA -1283\n(10 µg)\nN = 152SPIKEVAX\n(50 µg)\nN = 159Study  301 – Per-Protocol  Immunogenicity  Set (Randomly  Selected  Subset)\nDay 29 Day 91 Day 181\nGMR  (95%  CI) = 1.8 (1.4, 2.2) 1.8 (1.5, 2.3) 1.7 (1.3, 2.2)\n10000\n2340\n1. GMC  estimated  based  on ANCOVA  model\n© 2025  Moderna,  inc. All rights  reserved.\n18Neutralizing  Antibody  Responses  against  Omicron  XBB.1.5  \nwith mRNA -1283  Similar  to SPIKEVAX\nStudy  301 – Per-Protocol  Immunogenicity  Set - Japan\n•Study  assessed  safety  & immunogenicity  of monovalent  XBB.1.5  COVID -19 vaccine\nGMC1 (95%  CI)mRNA -1283\n(10 µg)\nN = 334SPIKEVAX\n(50 µg)\nN = 334 Geometric  Mean  Ratio  (GMR)  (95%  CI)\nOmicron  XBB.1.51757\n(1580,  1954)1470\n(1322,  1635)\n1\n1. GMC  estimated  based  on ANCOVA  model\n© 2025  Moderna,  inc. All rights  reserved.1.5 21.2 (1.03,  1.39)\n0.5 0.667\n•Lower  95% CI of GMR  was >0.667Noninferiority \nSuccess \nCriteria  Met\n© 2025  Moderna,  inc. All rights  reserved.\nRelative  Vaccine  Efficacy  of \nmRNA -1283  vs SPIKEVAX \n(mRNA -1273)\nStudy  30119\n20\nCOVID -19 Case  Definition  and Surveillance\nCDC  COVID -19 Definition1\n•Virologic  confirmation  of SARS -CoV -2 infection  via PCR\n•Presence  of ≥1 symptom  consistent  with COVID -19 within  14 days  of positive  PCR\n•Fever  or chills •Fatigue •Loss of taste  or smell\n•Cough •Muscle  or body  ache •Sore  throat\n•Shortness  of breath  or •Headache •Congestion  or runny  nose\ndifficulty  breathing•Nausea  or vomiting •Diarrhea\n•Biweekly  symptom  surveillance  conducted  using  an electronic  diary  prompt\n•Participants  with symptoms  seen  for clinical  evaluation  and collection  of respiratory  samples \nfor SARS -CoV -2 PCRCOVID -19 Surveillance\n© 2025  Moderna,  inc. All rights  reserved.1.  https://ndc.services.cdc.gov/case -definitions/coronavirus -disease -2019 -covid -19/\n21Prespecified  Success  Criteria  Met for Relative  Vaccine \nEfficacy  of mRNA -1283  vs SPIKEVAX\nPer-Protocol  Set for Efficacy  (Median  8 Months)\nParticipants  with \nCOVID -19, % [n/N]mRNA -1283\n(10 µg)SPIKEVAX\n(50 µg)Relative  Vaccine  Efficacy \nBased  on Hazard  Ratio  (99.4%  CI)1,2P-value3\nPrimary  rVE Objective \n(≥12 year)9.9%\n[560/5679]10.8%\n[617/5687]0.0005\n-30 -20 -10 0\n© 2025  Moderna,  inc. All rights  reserved.10 20 309.3%  (-6.6, 22.8)\n•Lower  bound  of two-sided  99.4%  (alpha -adjusted)  CI of rVE > -10% \n(1-sided  alpha  spending:  0.0028)Noninferiority \nSuccess \nCriteria  Met\nBased  on CDC  COVID -19 definition\n1rVE =1-hazard  ratio,  hazard  ratio  estimated  using  a stratified  Cox proportional  hazard  model  (stratified  by age group  at randomization)  and with treatment  group  as a fixed  effect.\n2Alpha -adjusted  2-sided  (99.4%)  CI was calculated  using  the Lan-DeMets  O’Brien -Fleming  Spending  function  (nominal  one-sided  alpha  of 0.0028)\n3P-value  based  on the stratified  Cox proportional  hazard  model  to test the null hypothesis  log (hazard  ratio)>=log(1.1)\n22Relative  Vaccine  Efficacy  of mRNA -1283  vs SPIKEVAX \nin Participants  by Age\nCOVID -19 Events1 through  31 Jan 2024  – Per-Protocol  Set for Efficacy\nParticipants  with \nCOVID -19, % [n/N]mRNA -1283\n(10 µg)SPIKEVAX\n(50 µg)Relative  Vaccine  Efficacy \nBased  on Hazard  Ratio  (95%  CI)1,2\n12-17 Years5.9%\n[29/491]4.7%\n[23/490]-29.2%  (-123.3,  25.3)\n18-64 Years10.7%\n[382/3558]11.8%\n[422/3562]9.7%  (-3.8, 21.3)\n≥ 65 Years9.1%\n[149/1630]10.5%\n[172/1635]13.5%  (-7.7, 30.6)\n-60 -40 -20 0 20 40 60\n•Highest  relative  vaccine  efficacy  in adults  ≥65 years\n•Limited  number  of COVID -19 cases  in 12-17-year -olds results  in imprecise  relative  vaccine  efficacy  estimate\n© 2025  Moderna,  inc. All rights  reserved.1.Based  on CDC  COVID -19 definition;  2. Posthoc analysis  of RVE in ≥50-year -olds (3399  received  mRNA -1283,  3431  received  mRNA -1273);\nrVE – relative  vaccine  efficacy  = 1-hazard  ratio,  hazard  ratio  was estimated  using  a Cox proportional  hazard  model  and with treatment  group  as a fixed  effect.\n23Relative  Vaccine  Efficacy  Favorable  for mRNA -1283  for \nIndividuals  with Comorbidities\nPost Hoc Analysis  – Based  on CDC  Definition  for COVID -19 Risk1\nParticipants  with \nCOVID -19, % [n/N]mRNA -1283\n(10 µg)SPIKEVAX\n(50 µg)Relative  Vaccine  Efficacy \nBased  on Hazard  Ratio  (95%  CI)1\n≥ 1 comorbidities10.2%\n[267/2617]12.4%\n[329/2658]17.5%  (3.0, 29.8)\nAnd ≥ 50 Years9.6%\n[169/1755]12.4%\n[228/1833]23.0%  (6.1, 36.9)\nAnd ≥ 65 years8.5%\n[78/913]11.8%\n[110/929]28.6%  (4.6, 46.6)\n-50 -40 -30 -20 -10\n© 2025  Moderna,  inc. All rights  reserved.0 10 20 30 40 50\n1. https:// www.cdc.gov/covid/risk -factors/index.html\n24Relative  Vaccine  Efficacy  of mRNA -1283  vs SPIKEVAX \nDemonstrated  in Prevention  of Severe  COVID -19\nPost Hoc Analysis  – Protocol  Set for Efficacy,  through  31 Jan 2024\n•SPIKEVAX  effective  in prevention  of severe  COVID -19 in pivotal  efficacy  trial and real-world \neffectiveness  studies1-3\n•55 cases  of severe  COVID -19 identified  in this trial\n•Severe  criteria  per FDA guidance  (originally  used  in mRNA -1273  efficacy  trial)1\n•Majority  (92.7%) of  severe  COVID -19 cases  were due  to blood  pressure  or oxygen  saturation \nabnormalities\nParticipants  with Severe \nCOVID -19, % [n/N]mRNA -1283\n(10 µg)SPIKEVAX\n(50 µg)Relative  Vaccine  Efficacy\n(95%  CI)\nAll Participants  (≥12 years)0.4%\n[21/5679]0.6%\n[34/5687]\n-50 0 50\n1. https: //www.fda.gov/regulatory -information/search -fda-guidance -documents/development -and-licensure -vaccines -prevent -covid -19; 2. Zheng  et al Intl J Inf Dis 2022;\n3. Link-Gelles  ACIP  2024.\nSevere  defined  as respiratory  failure/ARDS,  renal/hepatic/neurologic  dysfunction,  admission  to ICU/death,  or vital sign abnormalities  indicative  of severe  systemic  illness  or BP\nabnormalities  indicative  of shock  (respiratory  rate ≥30 per minute,  heart  rate ≥125  beats  per minute,  or SpO2  ≤93%  on room  air at sea level  or PaO2/FiO2  <300  mmHg,  systolic\nBP <90 mmHg,  diastolic  BP <60 mmHg,  or requiring  vasopressors)\n© 2025  Moderna,  inc. All rights  reserved.10038.1%  (-6.7, 64.1)\n© 2025  Moderna,  inc. All rights  reserved.\nSummary25\nSummary  - Next  Generation  COVID -19 Vaccine  mRNA -128326\nSafety •mRNA -1283  generally  well tolerated;  no safety  concerns  identified\n•Pre-specified  non-inferiority  objectives  met\n•mRNA -1283  elicited  higher  immune  responses  than  SPIKEVAX\n•GMR  highest  in participants  ≥65 years  old (GMR  1.8; 95% CI: 1.4, 2.2)Immunogenicity\n•Prespecified  rVE non-inferiority  objective  met\n9.3%  mRNA -1283  vs mRNA -1273;  99.4%  CI: -6.6, 22.8\n•Trend  for higher  rVE point  estimates  with advancing  age and comorbidity\n>65 years  old:\n13.5%  mRNA -1283  vs mRNA -1273;  95% CI: -7.7, 30.6\n>65 years  old and >1 comorbidity*  (Post hoc):\n28.6%  mRNA -1283  vs mRNA -1273;  95% CI: 4.6, 46.6Relative  Vaccine \nEfficacy  (rVE)\n•mRNA -1283  has the potential  to further  reduce  the burden  of COVID -19, particularly\namong  those  most  vulnerable  to severe  outcomesPublic  Health \nBenefit\n© 2025  Moderna,  inc. All rights  reserved.GMR  – geometric  mean  ratio  ;\n* Comorbidities  associated  with severe  COVID -19 outcomes https:// www.cdc.gov/covid/risk -factors/index.html\nTHANK  YOU!\n© 2025  Moderna,  inc. All rights  reserved.•Investigators\n•Study  site personnel\n•Laboratory  personnel\n•Most  importantly,  the individuals  who \nparticipated  in these  trials27", "summary": "Overview  of Moderna’s  Investigational   Next  Generation  COVID -19 Vaccine,  mRNA -1283,  in Individuals  ≥12 Years  of Age © 2025  Moderna,  inc. All rights  reserved.ACIP Bishoy  Rizkalla,  PhD  April  15, 20251 2 COVID -19 Remains  a Leading  Cause  of Hospitalization  among  Respiratory  Viruses  in the US Adults  ≥65 years  account  for: •>60%  of COVID -19 hospitalizations (since  2023 )2 •~76%  of deaths  (since  2020)3•95% of adults  hospitalized  with  COVID -19 have  ≥1…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/02-Rizkalla-COVID-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 27}
{"title": "03 Havers COVID 508", "content": "COVID -19–Associated Hospitalizations —\nCOVID -NET, April 2025 Update\nFiona P. Havers, MD, MHS, FIDSA\nRESP -NET Hospitalization Surveillance Team\nCoronavirus and Other Respiratory Viruses Division\nAdvisory Committee on Immunization Practices (ACIP) Meeting\nApril 15, 2025National Center for Immunization and Respiratory Diseases\n1\nCOVID -NET is a population -based hospitalization \nsurveillance platform.\n•RESP -NET: COVID -NET, RSV -NET, FluSurv -NET\n•>300 acute -care hospitals\n•98 counties in 13 states\n•~10% of the U.S. population\n•Positive SARS -CoV-2 test ≤14 days\nbefore admission or during\nhospitalization\n•Screening or clinician -driven testing\n•Clinical data: age - and site -stratified random sample\nCOVID -NET: https://www.cdc.gov/covid/php/covid -net/index.html   Some slides display data from 90 counties in 12 states due to incomplete data.2\n\n010203040\n20\n2020\n2120\n2220\n2320\n2420\n25Rates of COVID -19, influenza, and RSV hospitalization — RESP -NET, 2020 –2025\n2020 2021 2022 2023 2024 2025COVID -19 hospitalization rates have had both winter \nand summer peaks.\n30246810121416Hospitalizations per 100,000 populationWeekly Rates of COVID -19–, Influenza -, and RSV -Associated \nHospitalizations — RESP -NET, October 2023 –March 2025\nCOVID-19 Influenza RSV\nRates for all three pathogens (COVID -19, influenza, and respiratory syncytial virus [RSV]) are laboratory -confirmed. Data source : https://www.cdc.gov/resp -net/dashboard/  \nNote that rates are not adjusted for testing or limited to admissions where the respiratory infection is the likely primary r eason for admission. \nRates of COVID -19 hospitalizations for the 2024 –2025 \nseason are lower compared to last season.\n4050100150200250\nOct Nov Dec Jan Feb Mar Apr May Jun Jul Aug SepHospitalizations per 100,000 populationCumulative Rates of COVID -19–, Influenza -, and RSV -Associated Hospitalizations, by Surveillance Season* —\nRESP -NET, October 2023 –March 2025\nCOVID 2023 –2024 Influenza 2023 –2024 RSV 2023 –2024\nCOVID 2024 –2025 Influenza 2024 –2025 RSV 2024 –2025\n* Seasons are defined as October through September. The 2024 –2025 season shows data from October 2024 –March 2025 and is ongoing.\nRates for all three pathogens (COVID -19, influenza, and respiratory syncytial virus [RSV]) are laboratory -confirmed. Data source : https://www.cdc.gov/resp -net/dashboard/  \nNote that rates are not adjusted for testing or limited to admissions where the respiratory infection is the likely primary r eason for admission. \nCumulative COVID -19–associated hospitalization rates by \nsurveillance season — COVID -NET, March 2020 –March 2025\n* The 2019 –2020 surveillance period includes March –September 2020; other seasons are defined as October through September. The 2 024–2025 season shows data from October 2024 –\nMarch 2025 and is ongoing. 50100200300400500600\n2019 –2020 2020 –2021 2021 –2022 2022 –2023 2023 –2024 2024 –2025Hospitalization rate per 100,000 population\nRespiratory virus season*May–September\nOctober –April\nMany COVID -19-\nassociated \nhospitalizations \noccur outside of \nthe typical \nrespiratory virus \nseason.\nAmong all age groups, rates of COVID -19–associated \nhospitalizations have declined since the 2021 –2022 season.\n* The 2019 –2020 surveillance period includes March –September 2020; other seasons are defined as October through September. The 2 024–2025 season shows data from October 2024 –\nMarch 2025 and is ongoing. \n6050010001500200025003000\n*2019 –2020\n2020 –2021\n2021 –2022\n2022 –2023\n2023 –2024\n2024 –2025\n*2019 –2020\n2020 –2021\n2021 –2022\n2022 –2023\n2023 –2024\n2024 –2025\n*2019 –2020\n2020 –2021\n2021 –2022\n2022 –2023\n2023 –2024\n2024 –2025\n*2019 –2020\n2020 –2021\n2021 –2022\n2022 –2023\n2023 –2024\n2024 –2025\n*2019 –2020\n2020 –2021\n2021 –2022\n2022 –2023\n2023 –2024\n2024 –2025\n*2019 –2020\n2020 –2021\n2021 –2022\n2022 –2023\n2023 –2024\n2024 –2025\n*2019 –2020\n2020 –2021\n2021 –2022\n2022 –2023\n2023 –2024\n2024 –2025\n*2019 –2020\n2020 –2021\n2021 –2022\n2022 –2023\n2023 –2024\n2024 –2025\n<6 mo 6 mo –4 yrs 5–11 yrs 12–17 yrs 18–49 yrs 50–64 yrs 65–74 yrs ≥75 yrsRate per 100,000 population\nAge group and surveillance periodCumulative rates of COVID -19–associated hospitalizations — COVID -NET, March 2020 –March 2025\n\nRates of respiratory virus -associated hospitalizations vary \nby age group and pathogen.\n70200400600800100012001400160018002000\n<1 1–4 5–11 12–17 18–49 50–64 65–74 ≥75Rate per 100,000 population\nAge in yearsCumulative rates of COVID -19–, influenza -, and RSV -associated hospitalizations — \nRESP -NET, October 2023 –September 2024\nCOVID-19 Influenza RSV\nRates for all three pathogens (COVID -19, influenza, and respiratory syncytial virus [RSV]) are laboratory -confirmed. Data source : https://www.cdc.gov/resp -net/dashboard/  \nNote that rates are not adjusted for testing or limited to admissions where the respiratory infection is the likely primary r eason for admission. \nPediatric COVID -19–Associated \nHospitalizations\n8\nDuring 2024 –2025, children and adolescents comprised \nabout 4% of COVID -19–associated hospitalizations.\n90%10%20%30%40%50%60%70%80%90%100%Percent of COVID -19–associated hospitalizations\nSurveillance week end datePercent of monthly COVID -19–associated hospitalizations, by age group —\nCOVID -NET, March 2020 –March 2025\n≤4 years 5–11 years 12–17 years 18–49 years 50–64 years 65–74 years ≥75 years•≤17 years = 4.3% of \nCOVID -19–associated \nhospitalizations \nduring October 2024 –\nMarch 2025\n•≤4 years = 2.9%\n•5–11 years = 0.6%\n•12–17 years = 0.6%\n\nAmong all children and adolescents, rates of COVID -19–associated \nhospitalizations are highest among infants ages <6 months.\n10051015202530Rate per 100,000 population\nSurveillance week end dateWeekly rates of COVID -19–associated hospitalizations among children and adolescents ages ≤17 years — COVID -NET, October \n2022 –March 2025\n<6 months 6 months –4 years 5–11 years 12–17 yearsMarch 2020 –March 2025\n\nAmong all children and adolescents, rates of COVID -19 \nhospitalizations are highest among infants ages <6 months.\n11051015202530Rate per 100,000 population\nSurveillance week end dateWeekly rates of COVID -19–associated hospitalizations among children and adolescents ages 6 months —17 years —\nCOVID -NET, October 2022 –March 2025\n6 months –4 years 5–11 years 12–17 yearsMarch 2020 –March 2025\n\nAmong children and adolescents eligible for COVID -19 vaccines, \ncumulative rates of COVID -19–associated hospitalizations \nremain the highest among children ages 6 months –4 years.\n1201234Rate per 100,000 population\nSurveillance week end dateWeekly rates of COVID -19–associated hospitalizations — COVID -NET, October 2022 –March 2025\n6 months –4 years 5–11 years 12–17 yearsMarch 2020 –March 2025\n\nRates* of influenza and COVID -19–associated hospitalizations \namong children ages ≤17 years** — RESP -NET, 2014 –2024\n* Note that rates of influenza hospitalizations are adjusted for undertesting and under -detection. Rates of COVID -19 hospitaliza tions are not adjusted for undertesting \nor under -detection. Rates of COVID -19 hospitalization might be higher when adjusted for these factors.\n** Monitoring for influenza hospitalizations typically occurs during October through April; for COVID -19 hospitalizations, monit oring for a given respiratory season \nbegins in October and continues through the following September. For the 2019 –2020 period, monitoring for COVID -19 hospitalizati ons began in March 2020.\nHistorical flu data from https://www.cdc.gov/flu -burden/php/data -vis/past -seasons.html . Historical flu data are not available for the 2020 –2021 period. 13050100150200250\n2014 –2015\n2015 –2016\n2016 –2017\n2017 –2018\n2018 –2019\n2019 –2020\n2020 –2021\n2021 –2022\n2022 –2023\n2023 –2024\n2014 –2015\n2015 –2016\n2016 –2017\n2017 –2018\n2018 –2019\n2019 –2020\n2020 –2021\n2021 –2022\n2022 –2023\n2023 –2024\n0–4 years 5–17 yearsHospitalization rates per 100,000 \npopulationInfluenza\nCOVID-19\n\nAmong children ages ≤4 years, COVID -19–associated \nhospitalization rates during the 22 –23 and 23 –24 seasons were \nsimilar to those due to influenza.\n* Note that rates of influenza hospitalizations are adjusted for undertesting and under -detection. Rates of COVID -19 hospitaliza tions are not adjusted for undertesting \nor under -detection. Rates of COVID -19 hospitalization might be higher when adjusted for these factors.\n** Monitoring for influenza hospitalizations typically occurs during October through April; for COVID -19 hospitalizations, monit oring for a given respiratory season \nbegins in October and continues through the following September. For the 2019 –2020 period, monitoring for COVID -19 hospitalizati ons began in March 2020.\nHistorical flu data from https://www.cdc.gov/flu -burden/php/data -vis/past -seasons.html . Historical flu data are not available for the 2020 –2021 period. 14050100150200250\n2014 –2015 2015 –2016 2016 –2017 2017 –2018 2018 –2019 2019 –2020 2020 –2021 2021 –2022 2022 –2023 2023 –2024\n0–4 yearsHospitalization rates per 100,000 populationRates* of influenza and COVID -19–associated hospitalizations among children ages 0 –4 years,\nby season** — RESP -NET, 2014 –2024\nInfluenza\nCOVID-19\n\nAmong children aged 5 –17 years, COVID -19–associated \nhospitalization rates during the 22 –23 and 23 –24 seasons were \nlower than those due to influenza.\n* Note that rates of influenza hospitalizations are adjusted for undertesting and under -detection. Rates of COVID -19 hospitaliza tions are not adjusted for undertesting \nor under -detection. Rates of COVID -19 hospitalization might be higher when adjusted for these factors.\n** Monitoring for influenza hospitalizations typically occurs during October through April; for COVID -19 hospitalizations, monit oring begins in October and is conducted \nyear -round. For the 2019 –2020 period, monitoring for COVID -19 hospitalizations began in March 2020.\nHistorical flu data from https://www.cdc.gov/flu -burden/php/data -vis/past -seasons.html . Historical flu data are not available for the 2020 –2021 period. 15010203040506070\n2014 –2015 2015 –2016 2016 –2017 2017 –2018 2018 –2019 2019 –2020 2020 –2021 2021 –2022 2022 –2023 2023 –2024\n5–17 yearsHospitalization rates per 100,000 \npopulationRates* of influenza and COVID -19–associated hospitalizations among children ages 5 – ≤17 years, and \nseason** — RESP -NET, 2014 –2024\nInfluenza\nCOVID-19\n\nDuring October 2022 –April 2024, more older children hospitalized \nwith COVID -19 had underlying medical conditions compared with \nyounger age groups.\n16010203040\n6–23 months 2–4 years 5–11 years 12–17 yearsWeighted % of COVID -19–associated hospitalizations\nPrematurity* Asthma/Reactive airway disease Neurologic disorders\nObesity† Chronic lung disease, not including asthma Feeding tube dependence\nCardiovascular disease Immunocompromising conditions Blood disorders\nChronic metabolic diseases, including diabetes77% with ≥1 \nunderlying \ncondition42% with ≥1 \nunderlying \ncondition62% with ≥1 \nunderlying \ncondition79% with ≥1 \nunderlying \ncondition\n* Prematurity is only assessed for children aged <2 years. †Obesity is not calculated for children aged <2 years. Data are li mited to hospitalizations with COVID -19 as the likely \nreason for admission. Source: Pre -publication analysis from Rebecca Free and presented at IDWeek  2024. Data reflect the period of October 1, 2022 –April 30, 2024.\nAmong children and adolescents ages 6 months –17 years hospitalized with COVID -19,\n59% had ≥1 underlying condition.\n~1 in 5 children and adolescents with COVID -19–associated \nhospitalization are admitted to the intensive care unit (ICU)\nHospitalizations are limited to those with COVID -19 as the presenting complaint upon admission.212223\n2127\n051015202530\n<6 months 6 months –<2 \nyears2–4 years 5–11 years 12–17 yearsPercent of hospitalizationsPercent of children and adolescents with COVID -19–\nassociated hospitalizations admitted to the ICU,\nby age group — COVID -NET, July 2023 –March 2024\nDuring this period, 7 children with COVID -19–\nassociated hospitalization died in -hospital in the \nCOVID -NET catchment area. Age categoryAmong those \nadmitted to \nICU, % with no \nunderlying \nconditions\n<6 months 56%\n6–23 months 52%\n2–4 years 30%\n5–11 years 6%\n12–17 years 24%\n41% of children admitted to the ICU \nhad no underlying conditions, but this \nvaried by age group\nFewer than 5% of children and adolescents eligible to received \nCOVID -19 vaccinations and hospitalized with COVID -19 received \nthe most recently recommended COVID -19 vaccination. \nNo record of COVID -19 dose in past 12 months : No recorded doses of any COVID -19 vaccine dose in the 12 months preceding hospitalization . ≥1 vaccine dose in \nlast 12 months, but no 2023 –2024 dose:  Received at least one COVID -19 bivalent booster vaccination in the 12 months preceding hospitalizations, but no record of \nreceiving 2023 -2024 vaccine dose. 2023 –2024 vaccine dose: Received 2023 -2024 vaccine dose. Persons with unknown vaccination status are \nexcluded. Hospitalizations are limited to those with COVID -19 as the presenting complaint upon admission.90 9092\n8 73 2 35\n0102030405060708090100\n6 months –4 years 5–11 years 12–17 yearsPercent of hospitalizationsVaccination status among children and adolescents with COVID -19–associated hospitalizations,\nby age group — COVID -NET, October 2023 –September 2024\nNo record of COVID-19 vaccine in past 12 months ≥1 vaccine dose in last 12 months, but no 2023 –2024 dose 2023 –2024 dose\n\nSummary (Children and Adolescents)\n•Rates of COVID -19–associated hospitalizations are highest among youngest age groups.\n•Among children and adolescents ages 5 –17 years, rates of hospitalization are higher for \ninfluenza than COVID -19.\n•More than half (59%) of children and adolescents hospitalized with COVID -19 had ≥1 \nunderlying medical condition.\n-Proportion of children with ≥1 underlying condition increased with age.\n•Most common underlying conditions among children and adolescents hospitalized with \nCOVID -19 varied by age group.\n•Fewer than 5% of children and adolescents hospitalized with COVID -19 had received the \nmost recently recommended COVID -19 vaccination during the 23 -24 season. \n19\nCOVID -19–Associated Hospitalizations \nAmong Adults Ages ≥18 Years\n20\nAdults ages ≥65 years comprise more than 2/3 of all \nCOVID -19–associated hospitalizations among adults.\nDuring this same period of January 2024 through March 2025, children and adolescents ages 17 years and younger comprised 4% o f all COVID -19-associated hospitalizations.210%10%20%30%40%50%60%70%80%90%100%\n3/7/2020\n5/30/2020\n8/22/2020\n11/14/2020\n2/6/2021\n5/1/2021\n7/24/2021\n10/16/2021\n1/8/2022\n4/2/2022\n6/25/2022\n9/17/2022\n12/10/2022\n3/4/2023\n5/27/2023\n8/19/2023\n11/11/2023\n2/3/2024\n4/27/2024\n7/20/2024\n10/12/2024\n1/4/2025\n2/22/2025Percent of adults hospitalized with COVID -19\nSurveillance week end datePercent of weekly COVID -19–associated hospitalizations among \nadults ages ≥18 years, by age group —\nCOVID -NET, March 2020 –March 2025\n18–49 years 50–64 years 65–74 years ≥75 years≥75 years=48%\n≥65 years=68%\n\nAmong adults, rates of COVID -19–associated \nhospitalizations increase with age.\n22581624191410\n02004006008001000120014001600Rate per 100,000 population\nSurveillance  week end dateCumulative rates of COVID -19–associated hospitalizations — COVID -NET, October 2023 –September \n2024\n18–49 years 50–64 years 65–74 years ≥75 yearsAge groupRate ratio \nof ≥75 \nyears \nrelative to \nadult age \ngroups\n18–49 24.4\n50–64 8.7\n65–74 3.4\nRates among adults ages \n≥75 years are many times \nhigher compared to \nyounger adults. \nAmong adults ages ≥65 years, rates of COVID -19–associated \nhospitalization during recent years remained higher than rates \nof influenza –associated hospitalization.\n* Note that rates of influenza hospitalization for 2014 –2015 through 2023 –2024 are adjusted for undertesting and under -detection . Rates of influenza hospitalizations for 2024 –2025 (shown in \nlighter colors) and all COVID -19 hospitalizations are not adjusted for undertesting or under -detection. Rates of hospitalization  might be higher when adjusted for these factors.\n** Monitoring for influenza hospitalizations typically occurs during October through April; for COVID -19 hospitalizations, monit oring begins in October and is conducted year -round. For the 2019 –\n2020 period, monitoring for COVID -19 hospitalizations began in March 2020. \n*** Data for 2024 -2025 show data for October 2024 – March 2025 only as the season is ongoing. \nHistorical flu data from https://www.cdc.gov/flu -burden/php/data -vis/past -seasons.html . Historical flu data are not available for the 2020 –2021 period. 23020040060080010001200140016001800\n2014 –2015\n2015 –2016\n2016 –2017\n2017 –2018\n2018 –2019\n2019 –2020\n2020 –2021\n2021 –2022\n2022 –2023\n2023 –2024\n2024 –2025***\n2014 –2015\n2015 –2016\n2016 –2017\n2017 –2018\n2018 –2019\n2019 –2020\n2020 –2021\n2021 –2022\n2022 –2023\n2023 –2024\n2024 –2025***\n2014 –2015\n2015 –2016\n2016 –2017\n2017 –2018\n2018 –2019\n2019 –2020\n2020 –2021\n2021 –2022\n2022 –2023\n2023 –2024\n2024 –2025***\n18–49 years 50–64 years ≥65 yearsHospitalization rates per 100,000 \npopulationRates* of influenza and COVID -19–associated hospitalizations among adults \nages ≥18 years, by age group and season** — RESP -NET, 2014 –2025\nInfluenza COVID-19\n\nRisk for COVID -19–associated hospitalization is increased \namong community -dwelling adults ages ≥18 years with \nunderlying medical conditions.\nAbbreviations: RR, rate ratio; CI, confidence interval; COPD, chronic obstructive pulmonary disease.\n* “None” refers to having none of the conditions examined in this analysis ( asthma, COPD, diabetes, chronic kidney disease, coronary artery disease, stroke, severe obesity, and current smoking).\n** “Any condition” refers to having at least 1 of these conditions. Notes: Non -severe obesity is defined as BMI 30 –39kg/m². Severe obesity is defined as BMI ≥40kg/m². “Any condition” includes \nasthma, COPD, diabetes, chronic kidney disease, coronary artery disease, stroke, severe obesity, and current smoking. Rate ra tios were estimated using multivariable Poisson models adjusted for sex, \nand race/ethnicity. “Smoker (current)” Includes people who quit smoking within the past 12 months. Data are limited to hospit alizations where COVID -19 is the likely reason for admission. 240.1110100\nNone* Any\ncondition**Asthma COPD Chronic\nkidney\ndiseaseCoronary\nartery\ndiseaseDiabetes Stroke\n(history of)Obesity\n(non-severe)Obesity\n(severe)Smoker\n(current)Adjusted RR (log scale)Adjusted Rate Ratios for COVID -19–associated Hospitalizations among Community -Dwelling Adults Ages ≥18 Years,\nby Age Group — October 2022 –September 2023\n18–49 50–64 65–74 ≥75Patterned bars indicate CIs that include 1.0.\n\n~1 in 5 adults hospitalized due to COVID -19 were admitted to the \nintensive care unit (ICU)\n251822\n18\n613\n8\n211\n8\n0510152025\n18–49 years 50–64 years ≥65 yearsPercent of adults hospitalized with \nCOVID -19\nAge groupProportion of adults hospitalized with COVID -19 with interventions and outcomes,\nby age group — COVID -NET, October 2023 –May 2024\nICU admission Invasive mechical ventilation In-hospital death\nData are limited to hospitalizations where COVID -19 is a likely primary reason for admission. Deaths do not include other COVID -19-related deaths that might occur after a patient is \ndischarged to hospice or other deaths that occur soon after hospital discharge that could be attributable to COVID -19-related il lness. During this period, 80% of all adults hospitalized with COVID -19 who died in -hospital were ages ≥65 years. \nMost adults hospitalized with COVID -19 had received no COVID -19 \nvaccine since September 2022.\nData are limited to hospitalizations where COVID -19 is a likely primary reason for admission.2675\n6165\n4150\n1927\n202523\n7121533\n26\n01020304050607080\n18–49 50–64 65–74 ≥75 ≥65Percent of adults hospitalized with COVID -19\nAge group in yearsVaccination status among adults hospitalized with COVID -19, by age group —\nCOVID -NET, October 2023 –September 2024\nNo record of 2022 –2023 (bivalent) or 2023 –2024 formula\nReceived 2022 –2023 (bivalent), but not 2023 –2024 formula\nReceived 2023 –2024 formula\n\nAs of November 30, \n2024, only 30% of \nnursing home \nresidents had \nreceived a 2024 –2025 \nCOVID -19 vaccine.\n2758\n30\n18\n010203040506070\nInfluenza COVID-19 RSV% nursing home residents vaccinated\n* As of December 10, 2024. Reses et al. “Coverage with Influenza, Respiratory Syncytial Virus, and Updated COVID -19 Vaccines Amo ng Nursing Home Residents - National Healthcare Safety Network, United \nStates, November 2024“. MMWR, November 21,  2024. \n\nSummary (Adults) (slide 1 of 2)\n•Rates of COVID -19–associated hospitalizations are highest among oldest adult age \ngroups.\n•Adults aged ≥65 years comprise 68% of adult COVID -19–associated \nhospitalizations \n-Aged ≥75 years: 48% of adult hospitalizations \n•COVID -19-associated hospitalization rates decreased over time, but cumulative \nrates among adults aged ≥75 years for the 2023 -2024 season remained higher \nthan those experienced by any other adult age group for any previous season.\n•Risk of hospitalization with COVID -19 remains during summer months (May –Sept).\n•26% of adults ages ≥65 years hospitalized with COVID -19 received the \nrecommended 2023 -24 COVID -19 vaccine prior to hospitalization.\n28\nSummary (Adults) (slide 2 of 2)\n•Some underlying medical conditions increase the risk for COVID -19 \nhospitalization among adults\n-CKD, diabetes, and CAD increased risk in all adult age groups\n•Having none of the underlying medical conditions examined decreased the risk \nfor COVID -19–associated hospitalization across all adult age groups.\n•In general, the relative risk of COVID -19 hospitalization among adults with vs. \nwithout select conditions declined with age for most, but not all, conditions \nexamined.\nAbbreviations: CKD: chronic kidney disease; CAD: coronary artery disease; COPD: chronic obstructive pulmonary disease.29", "summary": "COVID -19–Associated Hospitalizations — COVID -NET, April 2025 Update Fiona P. Havers, MD, MHS, FIDSA RESP -NET Hospitalization Surveillance Team Coronavirus and Other Respiratory Viruses Division Advisory Committee on Immunization Practices (ACIP) Meeting April 15, 2025National Center for Immunization and Respiratory Diseases 1 COVID -NET is a population -based hospitalization  surveillance platform. •RESP -NET: COVID -NET, RSV -NET, FluSurv -NET •>300 acute -care hospitals •98 counties in 13…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/03-Havers-COVID-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 29}
{"title": "04 Link Gelles COVID 508", "content": "Interim Estimates of 2024 -2025 COVID -19 \nVaccine Effectiveness\nRuth Link -Gelles, PhD, MPH\nCDR, US Public Health Service\nCoronavirus and Other Respiratory Viruses Division\nCenters for Disease Control and Prevention \nApril 15, 2025National Center for Immunization and Respiratory Diseases \n\n2•Context for interpretation of VE\n•2024 -2025 COVID -19 vaccine coverage\n•Vaccine effectiveness methods\n•Interim 2024 -2025 COVID -19 vaccine effectiveness Agenda –COVID -19 vaccine effectiveness (VE)\n3•High rates of SARS -CoV-2 infection -induced immunity by October –December 2023.*Context for interpreting COVID -19 VE across age groups: high infection -\ninduced seroprevalence by end of 2023\n* Data on persons aged ≥16 years from a longitudinal, national cohort of ~35,000 blood donors.\nMethods and data available at: https://covid.cdc.gov/covid -data -tracker/#nationwide -blood -donor -seroprevalence -2022 89%\n92%\n87%\n76%16-29 years\n30-49 years\n50-64 years\n≥65 years\n0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%\nPercent with infection -induced immunityPercent of persons with infection -induced immunity,\nbased on anti -nucleocapsid results from blood donors\nVE findings should be interpreted as the added benefit  provided by COVID -19 vaccination in a \npopulation with a high prevalence of vaccine - and infection -induced immunity.\n4COVID -19 Vaccination Coverage Among Adults ≥18 Years, 65 -74 Years, \nand ≥75 Years, 2023 and 2024, NIS -ACM\n0255075100\nSep 7\nSep 14\nSep 21\nSep 28\nOct 5\nOct 12\nOct 19\nOct 26\nNov 2\nNov 9\nNov 16\nNov 23\nNov 30\nDec 7\nDec 14\nDec 21\nDec 28\nSep 7\nSep 14\nSep 21\nSep 28\nOct 5\nOct 12\nOct 19\nOct 26\nNov 2\nNov 9\nNov 16\nNov 23\nNov 30\nDec 7\nDec 14\nDec 21\nDec 28\nSep 7\nSep 14\nSep 21\nSep 28\nOct 5\nOct 12\nOct 19\nOct 26\nNov 2\nNov 9\nNov 16\nNov 23\nNov 30\nDec 7\nDec 14\nDec 21\nDec 28\nAdults ≥18 years Adults 65-74 years Adults ≥75 yearsVaccination coverage (%)\nWeek endingCOVID-19 vaccination coverage (2024) COVID-19 vaccination coverage (2023)\nSlide courtesy of CDC Immunization Services Division.\nNational Immunization Survey -Adult COVID Module: Data from adults age ≥18 years are collected by telephone interview using a random -digit -dialed sample of cell telephone numbers  stratified by \nstate, the District of Columbia, five local jurisdictions (Bexar County TX, Chicago IL, Houston TX, New York City NY, and Phi ladelphia County PA), and Puerto Rico and the U.S. Virgin Islands. Data are \nweighted to represent the non -institutionalized U.S. population and mitigate possible bias that can result from an incomplete sa mple frame (exclusion of households with no phone service or only \nlandline telephones) or non -response. All responses are self -reported. For more information about the survey, see https://www.cd c.gov/nis/about/index.html.\nMethods\n5\n6Measuring COVID -19 vaccine effectiveness\nMeasure Definition Example \nvaccinated\ngroupExample comparison group\nAbsolute VE Compares frequency of health \noutcomes in vaccinated and \nunvaccinated people Received  \noriginal \nmonovalent \nCOVID -19 \nvaccineReceived no COVID -19 vaccines ever\nRelative VE Compares frequency of health \noutcomes in people who \nreceived one type of vaccine to \npeople who received a different \nvaccineReceived  \nbivalent \nCOVID -19 \nvaccineEligible for, but did not receive, bivalent \nCOVID -19 vaccine , but received \noriginal monovalent COVID -19 \nvaccine\nVE of 2024 -2025  COVID -\n19 vaccines*Compares people who received \n2024 -2025  COVID -19 vaccine to \npeople who did not, regardless \nof past vaccinationReceived  \n2024 -25 doseEligible for, but did not receive, an \n2024 -25 dose , regardless of past \nvaccination history \n*Vaccine effectiveness was also measured this way for 2023 -2024 COVID -19 vaccines\n7VISION Multi -Site Network of Electronic Health Records\n>300 emergency departments and urgent cares and >200 hospitals \n▪Design: Test-negative design\n▪Population: Adults ≥18 years  visiting a participating \nemergency department or urgent care (ED/UC) or \nhospitalized with COVID -19-like illness (CLI) with a \nSARS -CoV-2 NAAT test result within 10 days before or \n72 hours after encounter\n−Cases : CLI with positive  NAAT or antigen for SARS -CoV-2 \nand no positive NAAT for RSV or influenza\n−Controls : CLI with negative  NAAT for SARS -CoV-2 and no \npositive NAAT for influenza (≥18 years) or RSV (≥60 years)\n▪Vaccination data: Documented by electronic health records and state and city \nregistries\nCLI = COVID -19-like illness; ED/UC = emergency department/urgent care; RSV = respiratory syncytial virus; NAAT = nucleic acid am plification test\nCLI is defined based on the presence of specific discharge diagnosis codes. Link -Gelles, et al. In press, MMWR.   \n8IVY Network —26 hospitals, 20 U.S. States\n•Design : Test-negative, case -control design\n•Population : Adults  aged  ≥65 years  hospitalized with COVID -\nlike illness (CLI)* and SARS -CoV-2 test results within 10 days of \nillness onset and 3 days of admission\n–Cases: CLI and test  positive  for SARS -CoV-2 by NAAT or antigen\n–Controls : CLI and test negative  for SARS -CoV-2, influenza and \nRSV by RT -PCR\n•Vaccination data: Electronic medical records (EMR), state and \ncity registries, and plausible self -report\n•Specimens: Nasal swabs  obtained on all patients for central \nRT-PCR testing and whole genome sequencing\n*CLI is defined as presence of any one of the following: fever, cough, shortness of breath, chest imaging consistent with pneumoni a, or hypoxemia\nNAAT = nucleic acid amplification test\n\nInterim Estimates of 2024 -2025 COVID -19 \nVaccine Effectiveness\n9\n10Characteristics of emergency department and urgent care encounters and hospitalizations \namong adults aged ≥18 years with COVID -19-like illness, by COVID -19 case status and CDC \nvaccine effectiveness network — VISION and IVY Networks\nSeptember 2024 –January 2025 \nCharacteristicVaccine effectiveness network and setting, no. (column %)\nVISION\nED/UC encounters,\nall adults aged ≥18 yearsVISION\nhospitalizations,\nall adults aged ≥65 yearsIVY\nhospitalizations,\nimmunocompetent adults aged ≥65 years\nTotalCOVID -19\ncase -\npatientsCOVID -19\ncontrol -\npatients TotalCOVID -19\ncase -\npatientsCOVID -19\ncontrol -\npatients TotalCOVID -19\ncase -\npatientsCOVID -19\ncontrol -\npatients\nTotal 137,543​ 10,459​ 127,084​ 34,411​ 2,846​ 31,565​ 1,929​ 683​ 1,246\nMedian age 53 [34, 72]​ 58 [37, 74]​ 53 [34, 71]​ 78 [72, 84]​ 79 [73, 86]​ 78 [71, 84]​ 77 [71, 84]​ 78 [72, 85]​ 76 [70, 83]\nAge group\n18-64 years 88,858 (65)​ 6,113 (58)​ 82,745 (65)​ -- -- -- -- --\n≥65 years 48,685 (35)​ 4,346 (42)​ 44,339 (35)​ 34,411 (100)​ 2,846 (100)​ 31,565 (100)​ 1,929 (100)​ 683 (100)​ 1,246 (100)\nImmunocompromised* -- -- -- 8,192 (24)​ 598 (21)​ 7,594 (24)​ -- --\nLink-Gelles, et al. MMWR: https://www.cdc.gov/mmwr/volumes/74/wr/mm7406a1.htm\nED/UC = emergency department/urgent care\n* Immunocompromised status is not evaluated for ED/UC encounters due to a higher likelihood of incomplete discharge diagnosis  codes in this setting.\n11Effectiveness of 2024 –2025 COVID -19 vaccination against COVID -19–associated emergency \ndepartment/urgent care encounters by age group — VISION Network\nSeptember 2024 – January 2025\nLink-Gelles, et al. MMWR: https://www.cdc.gov/mmwr/volumes/74/wr/mm7406a1.htm   \nVaccine effectiveness was calculated by comparing the odds of 2024 –2025 COVID -19 vaccination in case -patients and control -patien ts using the equation: (1 – adjusted odds ratio) x 100%. Odds ratios \nwere estimated by multivariable logistic regression. The odds ratio was adjusted for age, sex, race and ethnicity, calendar d ay, and geographic region. The “no 2024 –2025 dose” group included all \neligible persons who did not receive a 2024 –2025 COVID -19 vaccine dose, regardless of number of previous COVID -19 vaccine doses (if any) received.\n* Time since vaccination is for most recent dose, which could have been an original monovalent, bivalent, 2023 -2024, or 2024 -2025 COVID -19 vaccine.Age group/2024 -2025 COVID -19 vaccination \nstatus/days since doseCOVID -19\ncase -patients\nN (Col %)COVID -19\ncontrol -patients\nN (Col %)Median interval since\nlast dose among\nvaccinated*, days (IQR) Adjusted vaccine effectiveness (95% CI)\n≥18 years\nNo 2024 -2025 COVID -19 dose  (Ref) 9,545 (91) 108,972 (86) 998 (539 -1,142) Ref\nReceived 2024 -2025 COVID -19 dose 7–119 days earlier 914 (9) 18,112 (14) 55 (32 -80) 33 (28 -38) \n2024 -2025 COVID -19 dose , 7–59 days earlier 480 (5) 9,789 (8) 33 (20 -46) 36 (29 -42)\n2024 -2025 COVID -19 dose , 60–119 days earlier 434 (4) 8,323 (7) 82 (71 -97) 30 (22 -37) \n18-64 years\nNo 2024 -2025 COVID -19 dose  (Ref) 5,860 (96) 76,792 (93) 1,042 (751 -1,180) Ref \nReceived 2024 -2025 COVID -19 dose 7–119 days earlier 253 (4) 5,953 (7)  53 (29 -77) 30 (20 -39)\n2024 -2025 COVID -19 dose , 7–59 days earlier 134 (2) 3,379 (4) 32 (20 -45) 36 (23 -46) \n2024 -2025 COVID -19 dose , 60–119 days earlier 119 (2) 2,574 (3) 81 (70 -95) 21 (5 -35) \n≥65 years\nNo 2024 -2025 COVID -19 dose  (Ref) 3,685 (85) 32,180 (73) 750 (346 -1,076) Ref \nReceived 2024 -2025 COVID -19 dose 7–119 days earlier 661 (15) 12,159 (27) 57 (33 -82) 35 (29 -41)\n2024 -2025 COVID -19 dose , 7–59 days earlier 346 (8) 6,410 (14) 34 (21 -47) 36 (28 -44)\n2024 -2025 COVID -19 dose , 60–119 days earlier 315 (7) 5,749 (13) 83 (71 -97) 34 (25 -42) \n0 20 40 60 80 100\nVaccine effectiveness (%)\n12Effectiveness of 2024 –2025 COVID -19 vaccination against COVID -19–associated hospitalization  \namong immunocompetent  adults aged ≥65 years — VISION and IVY Networks\nSeptember 2024 – January 2025\nAge group/2024 -2025 COVID -19 vaccination \nstatus/days since doseCOVID -19 \ncase -\npatients\nN (Col %)COVID -19 \ncontrol -\npatients\nN (Col %)Median interval since\nlast dose among\nvaccinated*, days (IQR) Adjusted vaccine effectiveness (95% CI)\nVISION\nNo 2024 -2025 COVID -19 dose  (Ref) 2,016 (90) 19,198 (80) 775 (357 -1,084) Ref\nReceived 2024 -2025 COVID -19 dose 7–119 days earlier 232 (10)  4,773 (20) 53 (30 -77) 45 (36 -53)\n2024 -2025 COVID -19 dose , 7–59 days earlier 129 (6) 2,759 (12) 33 (20 -46) 42 (30 -52)\n2024 -2025 COVID -19 dose , 60–119 days earlier 103 (5) 2,014 (8) 81 (70 -94) 48 (36 -58) \nIVY\nNo 2024 -2025 COVID -19 dose  (Ref) 614 (90) 1,021 (82) Not available Ref\nReceived 2024 -2025 COVID -19 dose 7–119 days earlier 69 (10) 225 (18) 60 (31 –85) 46 (26 -60)\n2024 -2025 COVID -19 dose , 7–59 days earlier 41 (6) 105 (9) 31 (20 –45) 42 (14 -61)\n2024 -2025 COVID -19 dose , 60–119 days earlier 28 (4) 120 (11) 85 (72 –98) 47 (17 -67) \n0 20 40 60 80 100\nVaccine effectiveness (%)\nLink-Gelles, et al. MMWR: https://www.cdc.gov/mmwr/volumes/74/wr/mm7406a1.htm   \nVaccine effectiveness was calculated by comparing the odds of 2024 –2025 COVID -19 vaccination in case -patients and control -patien ts using the equation: (1 – adjusted odds ratio) x 100%. Odds ratios \nwere estimated by multivariable logistic regression. For VISION, the odds ratio was adjusted for age, sex, race and ethnicity , calendar day, and geographic region. For IVY, the odds ratio was adjusted \nfor age, sex, race and ethnicity, geographic region (U.S. Department of Health and Human Services Region) and calendar time ( biweekly intervals). The “no 2024 –2025 dose” group included all eligible \npersons who did not receive a 2024 –2025 COVID -19 vaccine dose, regardless of number of previous COVID -19 vaccine doses. \n*Time since vaccination is for most recent dose, which could have been an original monovalent, bivalent, 2023 -2024, or 2024 -2025  COVID -19 vaccine.\n13Effectiveness of 2024 –2025 COVID -19 vaccination against COVID -19–associated hospitalization  \namong immunocompromised  adults aged ≥65 years — VISION\nSeptember 2024 – January 2025\n2024 -2025 COVID -19 vaccination status/days since \ndoseCOVID -19 \ncase -\npatients\nN (Col %)COVID -19 \ncontrol -\npatients\nN (Col %)Median interval since\nlast dose among\nvaccinated, days (IQR) Adjusted VE (95% CI)\nVISION\nNo 2024 -2025 COVID -19 dose  (Ref) 524 (88) 5,885 (78) 720 (343 -1,064) Ref\nReceived 2024 -2025 COVID -19 dose 7–119 days earlier 74 (12) 1,709 (22) 53 (31 -78) 40 (21 -54) \n0 20 40 60 80 100\nVaccine effectiveness (%)\nLink-Gelles, et al. MMWR: https://www.cdc.gov/mmwr/volumes/74/wr/mm7406a1.htm  \nVaccine effectiveness was calculated by comparing the odds of 2024 –2025 COVID -19 vaccination in case -patients and control -patien ts using the equation: (1 – adjusted odds ratio) x 100%. Odds \nratios were estimated by multivariable logistic regression. For VISION, the odds ratio was adjusted for age, sex, race and et hnicity, calendar day, and geographic region. The “no 2024 –2025 dose” \ngroup included all eligible persons who did not receive a 2024 –2025 COVID -19 vaccine dose, regardless of number of previous COVI D-19 vaccine doses (if any) received. \n* Time since vaccination is for most recent dose, which could have been an original monovalent, bivalent, 2023 -2024, or 2024 -2025 COVID -19 vaccine.\n14•2024 -2025 COVID -19 vaccination provided additional protection against COVID -19-associated emergency \ndepartment and urgent care visits and hospitalizations compared to no 2024 -2025 vaccine dose.\n•2024 -2025 COVID -19 vaccination also provided additional protection against COVID -19-associated \nhospitalizations among adults aged ≥65 years with immunocompromising conditions.\n•VE should be interpreted as the added benefit of 2024 –2025 COVID -19 vaccination in a population with \nhigh levels of infection -induced immunity, vaccine -induced immunity, or both.    \n-Prior SARS -CoV-2 infection contributes protection against future disease, though protection wanes over time. \n-An increase in SARS -CoV-2 circulation in the United States during late summer 2024, just before the 2024 –2025 \nCOVID -19 vaccines were approved and authorized, may have resulted in higher population -level immunity \nagainst JN.1 -lineage strains, which could have resulted in lower measured VE than in a population with less \nrecent infection.Conclusions: effectiveness of 2024 -2025 COVID -19 \nvaccines\n15Acknowledgements \nCDC\nAmanda B. Payne\nLakshmi Panagiotakopoulos\nLauren Roper\nDiya Surie\nAmadea Britton\nAllison Ciesla\nFatimah Dawood\nJennifer DeCuir\nShikha Garg\nAmber Kautz\nNathaniel M. Lewis\nJosephine Mak\nMorgan Najdowski\nCaitlin Ray\nEmily Reeves\nAlexander Webber\nRyan WiegandVISION Collaborators\nWestat\nSarah Ball\nAngela Cheung\nSean Chickery\nPatrick Mitchell\nSarah Reese\nElizabeth Rowley\nJanet Watts\nZack Weber\nIntermountain Health\nKristin Dascomb\nKaiser Permanente Center for Health Research\nStephanie A. Irving\nKaiser Permanente Northern California\nNicola P. Klein\nRegenstrief\nShaun J. Grannis\nUniversity of Colorado\nToan C. Ong\nHealthPartners\nMalini B. DeSilva\nColumbia University\nKarthik NatarajanIVY Collaborators\nWesley H. Self\nYuwei Zhu\nAdam S. Lauring\nEmily T. Martin\nIthan  D. Peltan\nAdit A. Ginde \nNicholas M. Mohr\nKevin W. Gibbs\nDavid N. Hager\nMatthew E. Prekker  \nAmira Mohamed \nNicholas Johnson\nJay S. Steingrub  \nAkram Khan\nJamie R. Felzer  \nAbhijit Duggal\nJennifer G. Wilson\nNida Qadir \nChristopher Mallow\nJennie H. Kwon\nCristie  Columbus\nIvana A. Vaughn\nBasmah  Safdar Jarrod M. Mosier\nEstelle S. Harris\nJames D. Chappell\nNatasha Halasa  \nCassandra Johnson\n+ many more!", "summary": "Interim Estimates of 2024 -2025 COVID -19  Vaccine Effectiveness Ruth Link -Gelles, PhD, MPH CDR, US Public Health Service Coronavirus and Other Respiratory Viruses Division Centers for Disease Control and Prevention  April 15, 2025National Center for Immunization and Respiratory Diseases   2•Context for interpretation of VE •2024 -2025 COVID -19 vaccine coverage •Vaccine effectiveness methods •Interim 2024 -2025 COVID -19 vaccine effectiveness Agenda –COVID -19 vaccine effectiveness (VE)…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/04-Link-Gelles-COVID-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 15}
{"title": "05 Panagiotakopoulos COVID 508", "content": "Use of 2025 –2026 COVID -19 Vaccines:\nWork Group Considerations\nLakshmi Panagiotakopoulos, MD, MPH\nAdvisory Committee on Immunization Practices\nApril 15, 2025National Center for Immunization and Respiratory Diseases \n\n•Current recommendations for 2024 –2025 COVID -19 vaccines\n•Policy options for 2025 –2026 COVID -19 vaccine recommendations\n•Supporting data and Work Group interpretations\n•Discussion questions for committee Overview\n2\nCOVID -19 vaccine: ACIP Meeting Schedule\nOctober \n2024April 2025June 2025 \n(proposed)\n•Additional dose of 2024 -\n2025 COVID -19 vaccines \nin adults ages ≥65 years\n•Additional dose(s) of \n2024 -2025 COVID -19 \nvaccines in moderately \nto severely \nimmunocompromised \npersons ages ≥6 months•Moderna mRNA -1283 \nCOVID -19 vaccine\n•Epidemiology and risk \nfactors for COVID -19 \nhospitalizations\n•Vaccine effectiveness \nupdate\n•Work Group \nConsiderations \n•No vote scheduled•Vote on 2025 –2026 \nCOVID -19 vaccine \nrecommendations \n(including additional \ndose recommendations)\n3\nReview of 2024 –2025 COVID -19 vaccine policy\n•Children ages 6 months –4 years\n-Unvaccinated: Should receive a multidose initial series with a 2024 –2025 mRNA \nvaccine\n-Previously completed an initial series: Should receive 1 dose of a 2024 –2025 \nmRNA vaccine from the same manufacturer as the initial series\n•People ages 5 –64 years: \n-Should receive 1 dose of an age -appropriate 2024 –2025 COVID -19 vaccine* \n•People ages 65 years and older: \n-Should receive 2 doses of any 2024 –2025 COVID -19 vaccine, spaced 6 months \napart (minimum interval 2 months)**Overview of the current COVID -19 vaccination \nschedule: Routine vaccination\n*People ages 12 –64 years who are unvaccinated and receive the 2024 –2025 Novavax COVID -19 vaccine for initial vaccination should receive 2 doses of 2024 –2025 Novavax COVID -19 vaccine. \n**People ages 65 years and older who are unvaccinated and receive Novavax COVID -19 Vaccine for initial vaccination should receiv e 2 doses of 2024 –2025 Novavax COVID -19 vaccine followed by a \nthird dose of any 2024 –2025 COVID -19 vaccine dose 6 months after the second dose (minimum interval 2 months). \nhttps://www.cdc.gov/vaccines/covid -19/clinical -considerations/interim -considerations -us.html#routine -vaccination -guidance  5\n•Unvaccinated: \n-Should receive a multidose initial vaccination series with an age -appropriate \n2024 –2025 vaccine and receive 1 dose of 2024 –2025 6 months after completing \nthe initial series (minimum interval 2 months)\n•Previously completed an initial series: \n-Should receive 2 doses of an age -appropriate 2024 –2025 COVID -19 vaccine, \nspaced 6 months apart (minimum interval 2 months) \n•May receive additional age -appropriate 2024 –2025 COVID -19 vaccine \ndoses under shared clinical decision -making (minimum interval 2 \nmonths) Overview of the current COVID -19 vaccination \nschedule: Moderate or severe immunocompromise\n6https://www.cdc.gov/vaccines/covid -19/clinical -considerations/interim -considerations -us.html#immunocompromised  \nPolicy considerations for use of the 2025 –2026 \nCOVID -19 vaccine \nPolicy Options for 2025 –2026 COVID -19 vaccines:\nMulti -dose initial series\n8•Currently a multi -dose initial series is recommended for people ages 6 \nmonths –4 years and people with immunocompromise\n-Option 1: Maintain a universal vaccine policy for everyone ages ≥6 months that \nincludes the multi -dose initial series\n-Option 2: Narrow current vaccine recommendations and only maintain this series \nfor certain populations within these groups who we determine should be \nvaccinated\nPolicy Options for 2025 –2026 COVID -19 vaccines:\nAnnual COVID -19 vaccine doses\n9•Currently annual vaccines are recommended for everyone ages ≥6 \nmonths\n-Option 1: Maintain a universal vaccine policy for everyone ages ≥6 months\n-Option 2: Risk-based recommendation only for groups at increased risk of severe \nCOVID -19\n-Option 3: Combination of risk -based and universal vaccine recommendations \n(e.g., risked -based recommendation for ages 6 months -64 years and universal \nrecommendations for ages ≥65 years. \n•Persons ages ≥65 years\n-2 doses per year for most; may be more if previously unvaccinated and receiving \nNovavax or immunocompromised\n•Persons ages ≥6 months who are moderately or severely \nimmunocompromised\n-Initial series if unvaccinated or post -immune ablative therapy \n-Initial series is followed by 2 doses per year\n-Additional doses can be administered under shared clinical decision -makingPolicy Options for 2025 –2026 COVID -19 vaccines:\nSemi -annual COVID -19 vaccine doses\n10\n•How much increased risk is needed to be included in a risk -based \nrecommendation?\n•Increased risk of severe outcomes\n-Age\n-Underlying conditions\n-Pregnancy (also protects infants <6 months of age)\n•Risk of exposure\n-Healthcare workers\n-People living in long -term care facilities and other congregate settings\n-Other groups at risk of increased exposure or transmission?How to define who is at increased risk? \n11\n•Asthma\n•Cancer\n-Hematologic Malignancies\n•Cerebrovascular disease\n•Chronic kidney disease*\n-People receiving dialysis^\n•Chronic lung diseases limited to:\n•Bronchiectasis\n•COPD (Chronic obstructive pulmonary disease)\n•Interstitial lung disease\n•Pulmonary embolism\n•Pulmonary hypertension\n• Chronic liver diseases limited to:\n•Cirrhosis\n•Non -alcoholic fatty liver disease•Alcoholic liver disease\n•Autoimmune hepatitis\n•Cystic fibrosis\n•Diabetes mellitus, type 1\n•Diabetes mellitus, type 2*\n•Disabilities‡,**, including Down \nsyndrome\n•Heart conditions (such as heart failure, \ncoronary artery disease, or \ncardiomyopathies)\n•HIV (Human immunodeficiency virus)\n•Mental health conditions limited to:\n•Mood disorders, including depression\n•Schizophrenia spectrum disorders•Neurologic conditions limited to \ndementia‡ and Parkinson’s Disease\n•Obesity (BMI >30 kg/m2or \n>95thpercentile in children)\n•Physical inactivity\n•Pregnancy and recent pregnancy\n•Primary immunodeficiencies\n•Smoking, current and former\n•Solid organ or blood stem cell \ntransplantation\n•Tuberculosis\n•Use of corticosteroids or other \nimmunosuppressive medicationsHigher Risk of Severe Illness of COVID -19 (conclusive)\n* Indicates presence of evidence for pregnant and non -pregnant women\n‡ Underlying conditions for which there is evidence in pediatric patients\n^ Risk may be further increased for people receiving dialysis\n** Attention -deficit/hyperactivity disorder (ADHD), Autism, Cerebral palsy, Charcot foot, Chromosomal disorders, Chromosome 17 a nd 19 deletion, Chromosome 18q deletion, Cognitive impairment, Congenital \nhydrocephalus, Congenital malformations, Deafness/hearing loss, Disability indicated by Barthel Index, Down syndrome, Fahr's  syndrome, Fragile X syndrome, Gaucher disease, Hand and foot disorders, Learning \ndisabilities, Leber's hereditary optic neuropathy (LHON) or Autosomal dominant optic atrophy (ADOA), Leigh syndrome, Limitati ons with self -care or activities of daily living, Maternal inherited diabetes and \ndeafness (MIDD), Mitochondrial encephalopathy, lactic acidosis, and stroke -like episodes (MELAS) and risk markers, Mobility disa bility, Movement disorders, Multiple disability (referred to in research papers as \n\"bedridden disability\"), Multisystem disease, Myoclonic epilepsy with ragged red fibers (MERRF), Myotonic dystrophy, Neurodev elopmental disorders, Neuromuscular disorders, Neuromyelitis optica  spectrum \ndisorder (NMOSD), Neuropathy, ataxia, and retinitis pigmentosa (NARP), Perinatal spastic hemiparesis, Primary mitochondrial m yopathy (PMM), Progressive supranuclear palsy, Senior -Loken  syndrome, Severe \nand complex disability (referred to in research papers as \" polyhandicap  disability\"), Spina bifida and other nervous system anomalies, Spinal cord injury, Tourette syndrome, Traumatic brain injury,  Visual \nimpairment/blindness, Wheelchair use \nhttps://www.cdc.gov/covid/hcp/clinical -care/underlying -conditions.html  12\n•Asthma\n•Cancer\n-Hematologic Malignancies\n•Cerebrovascular disease\n•Chronic kidney disease *\n-People receiving dialysis^\n•Chronic lung diseases limited to:\n•Bronchiectasis\n•COPD (Chronic obstructive pulmonary disease)\n•Interstitial lung disease\n•Pulmonary embolism\n•Pulmonary hypertension\n• Chronic liver diseases limited to:\n•Cirrhosis\n•Non -alcoholic fatty liver disease•Alcoholic liver disease\n•Autoimmune hepatitis\n•Cystic fibrosis\n•Diabetes mellitus, type 1\n•Diabetes mellitus, type 2 *\n•Disabilities‡,**, including Down \nsyndrome\n•Heart conditions (such as heart failure, \ncoronary artery disease, or \ncardiomyopathies)\n•HIV (Human immunodeficiency virus)\n•Mental health conditions  limited to:\n•Mood disorders, including depression\n•Schizophrenia spectrum disorders•Neurologic conditions limited to \ndementia‡ and Parkinson’s Disease\n•Obesity (BMI >30 kg/m2or \n>95thpercentile in children)\n•Physical inactivity\n•Pregnancy  and recent pregnancy\n•Primary immunodeficiencies\n•Smoking, current and former\n•Solid organ or blood stem cell \ntransplantation\n•Tuberculosis\n•Use of corticosteroids or other \nimmunosuppressive medicationsHigher Risk of Severe Illness of COVID -19 (conclusive)\n* Indicates presence of evidence for pregnant and non -pregnant women\n‡ Underlying conditions for which there is evidence in pediatric patients\n^ Risk may be further increased for people receiving dialysis\n** Attention -deficit/hyperactivity disorder (ADHD), Autism, Cerebral palsy, Charcot foot, Chromosomal disorders, Chromosome 17 a nd 19 deletion, Chromosome 18q deletion, Cognitive impairment, Congenital \nhydrocephalus, Congenital malformations, Deafness/hearing loss, Disability indicated by Barthel Index, Down syndrome, Fahr's  syndrome, Fragile X syndrome, Gaucher disease, Hand and foot disorders, Learning disabilities, \nLeber's hereditary optic neuropathy (LHON) or Autosomal dominant optic atrophy (ADOA), Leigh syndrome, Limitations with self -care or activities of daily living, Maternal inherited diabetes and deafness (MIDD), \nMitochondrial encephalopathy, lactic acidosis, and stroke -like episodes (MELAS) and risk markers, Mobility disability, Movement disorders, Multiple disability (referred to in research papers as \"bedridden disability\"), \nMultisystem disease, Myoclonic epilepsy with ragged red fibers (MERRF), Myotonic dystrophy, Neurodevelopmental disorders, Neu romuscular disorders, Neuromyelitis optica  spectrum disorder (NMOSD), Neuropathy, \nataxia, and retinitis pigmentosa (NARP), Perinatal spastic hemiparesis, Primary mitochondrial myopathy (PMM), Progressive sup ranuclear palsy, Senior -Loken  syndrome, Severe and complex disability (referred to in research \npapers as \" polyhandicap  disability\"), Spina bifida and other nervous system anomalies, Spinal cord injury, Tourette syndrome, Traumatic brain injury,  Visual impairment/blindness, Wheelchair use \nBolded conditions were included in analysis on prevalence of risk conditions by the Center for Forecasting Analytics (unpubli shed data); those highlighted by the red boxes were not included\nhttps://www.cdc.gov/covid/hcp/clinical -care/underlying -conditions.html  13\nEstimates of adults in the United States with at least 1 \ncondition that puts them at higher risk of severe illness from \nCOVID -19, by age group, October 2022 –September 2023\n67%65% 65%81%83%86%\n74%\n0%10%20%30%40%50%60%70%80%90%100%\n18-29 years 30-39 years 40-49 years 50-64 years 65-74 years ≥75 years ≥18 years\nUnpublished results from September 2024 analysis of medical claims data, consumer data, Behavioral Risk Factors Surveillance System, and/or National Health Interview Survey to enumerate \nthe US population with conditions that put them at increased risk of severe illness from COVID -19 using multilevel regression mo deling, CDC Center for Forecasting and Outbreak Analytics\n14\nSummary of supporting evidence\nCOVID -19 Epidemiology\nWeighted and Nowcast SARS -CoV-2 estimates in the United \nStates for 2 -week periods, December 2, 2024 –April 12, 2025\nThese data include Nowcast estimates, which are modeled predictions that may differ from weighted estimates generated at late r dates\nhttps://covid.cdc.gov/covid -data -tracker/#variant -proportions  Accessed April 14, 2025 17\n\nWeekly rates of COVID -19–associated hospitalizations in the \nUnited States by age group, October 2024 –March 2025\n1802468101214161820\nOctober November December January February MarchHospitalizations per 100,000 populationCrude Weekly Rates of COVID -19–Associated Hospitalizations, by Age Group —\nCOVID -NET, October 2024 –March 2025\n5–17 years 18–49 years 50–64 years ≥65 years\nRates for SARS -CoV-2 are laboratory -confirmed.\nNote that rates are not adjusted for testing or limited to admissions where the respiratory infection is the likely primary r eason for admission. \nData source: https://www.cdc.gov/resp -net/dashboard/  Accessed April  7, 2025 \nWeekly rates of respiratory virus -associated hospitalizations in \nthe United States among children ages 0 –17 years, 2023 –2025\n19024681012\nOct Nov Dec Jan Feb Mar Apr May Jun Jul Aug SepHospitalizations per 100,000 populationCrude Weekly Rates of COVID -19–, Influenza, and RSV -Associated Hospitalizations, by Surveillance Season* —\nRESP -NET, October 2023 –March 2025\nCOVID 2024 –2025 COVID 2023 –2024\nInfluenza 2024 –2025 Influenza 2023 –2024\nRSV 2024 –2025 RSV 2023 –2024\nRates for all three pathogens (COVID -19, influenza, and respiratory syncytial virus [RSV]) are laboratory -confirmed. \nNote that rates are not adjusted for testing or limited to admissions where the respiratory infection is the likely primary r eason for admission.\nData source: https://www.cdc.gov/resp -net/dashboard/  accessed April  7, 2025 \nWeekly number of COVID -19 deaths reported to CDC, \nUnited States, January 1, 2024 – March 29, 2025\nThe most recent 3 weeks of mortality counts are shaded grey because NVSS reporting is  <95% during this period.\nProvisional data are non -final counts of deaths based on reported mortality data in NVSS. Deaths include those with COVID -19, co ded as ICD –10 code U07.1, on the death certificate. Death data \nare displayed by date of death (event). Data include underlying and contributing causes of death.\nCDC COVID Data Tracker. National Center for Health Statistics (NCHS) National Vital Statistics System (NVSS). https://covid.cdc.gov/covid -data -tracker/#trends_weeklydeaths_select_00  . \nAccessed April 7, 2025 2005001,0001,5002,0002,5003,000\n1/6/2024 3/6/2024 5/6/2024 7/6/2024 9/6/2024 11/6/2024 1/6/2025 3/6/2025Weekly DeathsProvisional COVID -19 Deaths, by Week, in The United States, Reported to CDC\nTop 10 leading causes of death in the United States, \nchildren and adolescents 0 –17 years\nUnpublished data, CDC National Center for Health Statistics\n211. Certain conditions originating in \nthe perinatal period\n2. Accidents (unintentional injuries)\n3. Congenital malformations, \ndeformations, and chromosomal \nabnormalities\n4. Homicide\n5. Suicide\n6. Cancer\n7. Heart disease\n8. COVID -19\n9. Influenza and Pneumonia\n10. Septicemia1. Certain conditions originating in \nthe perinatal period\n2. Accidents (unintentional injuries)\n3. Congenital malformations, \ndeformations, and chromosomal \nabnormalities\n4. Homicide\n5. Suicide\n6. Cancer\n7. Heart disease\n8. COVID -19\n9. Influenza and Pneumonia\n10. Septicemia1. Certain conditions originating in \nthe perinatal period\n2. Accidents (unintentional injuries)\n3. Congenital malformations, \ndeformations, and chromosomal \nabnormalities\n4. Homicide\n5. Suicide\n6. Cancer\n7. Heart disease\n8. Influenza and Pneumonia\n9. Septicemia\n10. Stroke…\n12. COVID -19      2021                        2022                                       2023\nTop 10 leading causes of death in the United States, \nadults ages ≥18 years\nInfluenza and pneumonia was ranked 9th pre-pandemic in 2019; ranked 13th in 2023\nUnpublished data, CDC National Center for Health Statistics221. Heart disease\n2. Cancer\n3. COVID -19\n4. Accidents\n5. Chronic lower respiratory diseases\n6. Stroke\n7. Alzheimer’s disease\n8. Diabetes mellitus\n9. Chronic liver disease and cirrhosis\n10. Kidney disease1. Heart disease\n2. Cancer1. Heart disease\n2. Cancer\n3. Accidents\n4. Chronic lower respiratory diseases\n5. Stroke\n6. Alzheimer’s disease\n7. Diabetes mellitus\n8. Kidney disease\n9. Chronic liver disease and cirrhosis\n10. COVID -193. Accidents\n4. COVID -19\n5. Chronic lower respiratory diseases\n6. Stroke\n7. Alzheimer’s disease\n8. Diabetes mellitus\n9. Kidney disease\n10. Chronic liver disease and cirrhosis   2021                          2022                                          2023\nTotal number of COVID -19 deaths,1,2 September 2023 –\nAugust 2024, by age group, United States\n53 43 561,0283,36436,357\n05,00010,00015,00020,00025,00030,00035,00040,000\n<1 year 1–4 years 5–17 years 18–49 years 50–64 years ≥65 yearsNumber of Deaths\n1. Provisional data \n2. Underlying cause of death Source: Centers for Disease Control and Prevention, National Center for Health Statistics. Natio nal Vital Statistics System, Provisional Mortality on CDC WONDER Online \nDatabase. Data are from the final Underlying Cause of Death Files, 2018 -2023, and from provisional data for 2024, as compiled fr om data provided by the 57 vital statistics jurisdictions through the Vital \nStatistics Cooperative Program. Number of deaths includes COVID -19 code (U07.1) as the underlying cause of death. http://wonder.cdc.gov/mcd -icd10 -provisional.html , accessed January 16, 2025 \n23\nTotal number of COVID -19 and Influenza deaths1,2, among \nages 0 –17 years, September 2023 –August 2024, United States\n53\n4356\n1861134\n020406080100120140160\n<1 year 1–4 years 5–17 yearsNumber of Deaths\nCOVID-19 Influenza\n1. Provisional data \n2. Underlying cause of death Source: Centers for Disease Control and Prevention, National Center for Health Statistics. Natio nal Vital Statistics System, Provisional Mortality on CDC WONDER Online \nDatabase Data are from the final Underlying Cause of Death Files, 2018 -2023, and from provisional data for 2024, as compiled fro m data provided by the 57 vital statistics jurisdictions through the Vital \nStatistics Cooperative Program. Number of deaths includes influenza codes (J09 -J11) or COVID -19 code (U07.1) as the underlying c ause of death. http://wonder.cdc.gov/mcd -icd10 -provisional.html , \naccessed January 16, 2025 \nNote: Estimates of pediatric influenza deaths reported to CDC can be found here: https://www.cdc.gov/flu/weekly/index.htm . Estimates will vary due to differences in reporting methods and timeframes \nused.24\nCOVID -19—associated changes from 2023 –2024 to \n2024 –2025\n2023 –2024 2024 –2025 Difference\nRoutine vaccine recommendation6 months and older\n65 and older: 2 doses 6 months and older\n65 and older: 2 doses No change\nVaccine coverage <18 years1 13.8% (13.4 –14.3)\n(3/23/2024)12.8% (12.2 –13.4)\n(3/22/2025)Similar\nVaccine coverage ≥18 years2 21.3% (21.0 –21.5)\n(3/23/2024)23.1% (22.5 –23.7)\n(3/22/2025)Similar\nVaccine coverage ≥65 years2 37.5% (36.7 –38.3)\n(3/23/2024)44.0% (42.5 –45.4)\n(3/22/2025)Increase\nVaccine effectiveness against \nhospitalization, immunocompetent adults \n≥65 yearsVISION: 42% (37 –47)3\nIVY: 35% (20 –47)3VISION: 45% (36 –53)4\nIVY: 46% (26 –60)4Similar\nCumulative hospitalization rates (week 13)5125.6/100,000 62.9/100,000 Decrease\n1 https://www.cdc.gov/covidvaxview/weekly -dashboard/child -coverage -vaccination.html , accessed April 7, 2025\n2 https://www.cdc.gov/covidvaxview/weekly -dashboard/adult -vaccination -coverage.html , accessed April 7, 2025\n3 https://www.cdc.gov/acip/downloads/slides -2024 -06-26-28/03 -COVID -Link-Gelles -508.pdf ; median (IQR) days since dose: VISION: 84 (46 –127)  IVY: 81 (43 –121) \n4 Link-Gelles R, Chickery S, Webber A, et al. Interim Estimates of 2024 –2025 COVID -19 Vaccine Effectiveness Among Adults Aged ≥18 Years — VISION and IVY Networks, September 2024 –\nJanuary 2025. MMWR Morb  Mortal Wkly  Rep 2025;74:73 –82. M edian (IQR) days since dose – VISION: 53 (30 –77)  IVY: 60 (31 –85) \n5 https://covid.cdc.gov/covid -data -tracker/#covidnet -hospitalization -network , accessed April  7, 202525\nInfection -induced SARS -CoV-2 seroprevalence among U.S. \nchildren — September 2021 – December 2022\n26\nInfection -induced (nucleocapsid \nantibody) seroprevalence\nMonth and Year\nShaded ranges depict 95% confidence intervals for the estimated seroprevalence shown by the dark line in the corresponding co lor. \nSource: https://covid.cdc.gov/covid -data -tracker/#pediatric -seroprevalence   \nAccessed: March 20, 2025\nPopulation SARS -CoV-2 spike antibody over time by the cumulative \nnumber of combined infections and vaccinations - U.S. blood donors ages \n≥16 years, September 2021 -December 2023\nSolid lines represent mean anti -spike IgG levels; dotted lines represent model based 25th-75th% percentiles\nHigher number of cumulative SARS -CoV-2 infections and COVID -19 vaccinations leads to \nhigher antibody levels, but with smaller incremental increases in antibodies with each \nexposure\nSpike IgG BAU/mL\nSource: https://covid.cdc.gov/covid -data -tracker/#nationwide -blood -donor -seroprevalence -2022 , CDC unpublished data 27\nAmong  adults  aged ≥18 years, 3.6% \nreported Long COVID \nsymptoms, and 8.4%  reported ever \nhaving Long COVID1\nMore than 3 in 5 adults with Long \nCOVID report activity limitations1\nAmong  children aged 0 -17 \nyears, 0.4% reported Long COVID \nsymptoms, and 1.4% reported ever \nhaving Long COVID2Long COVID is a significant public health threat\n1. Vahratian  A,Saydah S, Bertolli J, Unger ER, Gregory CO. Prevalence of Post –COVID -19 Condition and Activity -Limiting Post –COVID -19 Condit ion Among Adults. JAMA Netw  Open. 2024;7(12):e2451151.\n2. Ford ND, Vahratian  A,Pratt CQ, Yousaf AR, Gregory CO, Saydah S. Long COVID Prevalence and Associated Activity Limitation in US Children. JAMA Pediatr .Published online February 03, 2025.National surveys in 2023 estimated  approximately 9.2 million adults and 0.3 million \nchildren in the U.S. had Long COVID.\n  \nAlmost 4 in 5 children with Long \nCOVID report activity limitations2\n28\n1. Yousaf AR, Mak J, Gwynn L, et al. COVID -19 Vaccination and Odds of Post –COVID -19 Condition Symptoms in Children Aged 5 to 17 Years. JAMA Netw Open. 2025;8(2):e2459672.\n2. Mak J, Khan S, Britton A et al. Association of Messenger RNA Coronavirus Disease 2019 (COVID -19) Vaccination and Reductions i n Post COVID Conditions Following Severe Acute Respiratory Syndrome \nCoronavirus 2 Infection in a US Prospective Cohort of Essential Workers, The Journal of Infectious Diseases, Volume 231, Issu e 3, 15 March 2025, Pages 665 –676COVID -19 mRNA vaccination associated with reduced occurrence of \nLong COVID following COVID -19: June 2021 -September 2022\nAmong children aged 5 – 17 years:\nCompletion of the primary vaccine \nseries prior to infection associated \nwith reduced likelihood of Long \nCOVID symptoms1\n•57% for 1 or more symptoms\n•73% for 2 or more symptoms\n•72% for respiratory symptomsAmong adults: \n3 doses of original monovalent vaccine \nprior to infection associated with \nreduced likelihood of Long COVID \nsymptoms2\n•63% for gastrointestinal symptoms\n•44% for neurological symptoms \n•52% for other non -specific symptoms \n29\nMultisystem Inflammatory Syndrome in Children (MIS -C) \nU.S. Incidence Over Time\n•US incidence of MIS -C by SARS -CoV-2 variant -predominant periods was previously \npublished1, updated data shown below\n-Defined using surveillance data and allowing for 2 weeks to MIS -C onset from when a variant \nexceeded 50% circulating lineages\n1. Yousaf AR, et al,  MMWR 2023\n2. Shingleton  J et al, Journal of Infection , 2022.\n3. Cohen JM, et al. Clin Infect Dis . 2023\n4. Whittaker R et al. Pediatrics.  2022Variant predominant \nperiodDates Number of \nMIS-C casesIncidence per 1,000,000 \n(95% CI) person -yearsMedian age \n(IQR), years\nPre-Delta Oct 15, 2020 –Apr 5, 2021 3,287 6.80 (6.57 –7.03) 9.2 (5.4 –13.1 )\nDelta Jul 10 –Dec 24, 2021 2,305 4.91 (4.71 –5.11) 9.1 (5.5 –12.3)\nOmicron BA.1/BA 1.1 Jan 1 –Apr 8, 2022 1,148 4.21 (3.97 –4.46) 7.5 (4.1 –11.5)\nOmicron BA.2/BA.4/BA.5 Apr 9 –Dec 31, 2022 428 0.57 (0.52 –0.63) 5.4 (2.9 –9.7)\nOmicron XBB.1.5 Jan 1 –Dec 31, 2023 141 0.14 (0.12 –0.16) 6.9 (3.7 –11.5)\nOmicron JN.1/others Jan 1 -Dec 31, 2024 79 0.08 (0.06 - 0.10) 9.1 (4.7 -14.3)\n•Similarly decreased incidence was observed in other countries2-4\n30\nCOVID -19 Vaccination Status of 2023 and 2024 U.S. Multisystem \nInflammatory Syndrome in Children (MIS -C) Cases\n•Although 95% of children with MIS -C in 2023 and 99% in 2024 were eligible to receive a COVID -19 \nvaccine ≥16 weeks before their MIS -C illness, only 19% in 2023 and 26% in 2024 of eligible children \nreceived any vaccine dose​\n•Of the 25 vaccinated children in 2023 with information on timing, 65% in 2023 received their last \nvaccine dose more than 12 months prior to MIS -C onset\n•All vaccinated children in 2024 received their last vaccine dose > 12 months prior to MIS -C onset\nYousaf AR et al, MMWR 2023 and unpublished data2023 Illness Onset \nN=141 (%)2024 Illness Onset \nN=79 (%)\nVaccine age -eligible¹ at time of MIS -C onset 134 (95) 78 (99)\nNo vaccination 108/134 (81) 58/78 (74)\nVaccinated (at least one dose received) 26/134 (19) 20/78 (26)\nLast vaccine dose >12 months before MIS -C onset 17/26 (65) 20/20 (100)\n¹10 months of age at onset considered the minimum age by which a child could plausibly have completed an mRNA primary vaccina tion series, with 6 months \nbeing the earliest possible age at first dose and ≥12 weeks from first dose required to complete a 3 -dose primary series, and 4 weeks between time since last \ndose and hospitalization\n31\nCOVID -19 Vaccine and Myocarditis\nCOVID -19 vaccine prescribing information or fact sheet \nwarnings and precautions about myocarditis and pericarditis\nhttps://www.fda.gov/emergency -preparedness -and-response/coronavirus -disease -2019 -covid -19/covid -19-vaccines -2024 -2025     Manufacturer Precaution\nPfizer Post marketing data with authorized or approved mRNA COVID -19 \nvaccines demonstrate increased risks of myocarditis and pericarditis, \nparticularly within the first week following vaccination. For COMIRNATY , \nthe observed risk is highest in males 12 through 17 years of age.\nModerna Post marketing data with authorized or approved mRNA COVID -19 \nvaccines demonstrate increased risks of myocarditis and pericarditis, \nparticularly within the first week following vaccination. For SPIKEVAX, \nthe observed risk is highest in males 18 years through 24 years of age.\nNovavax Clinical trials data provide evidence for increased risks of myocarditis and \npericarditis following administration of Novavax COVID -19 Vaccine, \nAdjuvanted.\n33\nMyocarditis following mRNA COVID -19 vaccination among \npeople ages 12 –39 years in the Vaccine Safety Datalink\n*Statistically significant increased rate ratio in vaccinated concurrent comparator analysis\nSource: CDC Immunization Safety Office, unpublished data 638\n25\n25\n2\nDose 1\nOriginal monovalentDose 2\nOriginal monovalentBooster\nOriginal monovalentBivalent\n2020-2021 2021-2022 2022-2023 2023-2024 2024-202538\n6\n22Incidence of myocarditis within 7 days of vaccination per million mRNA vaccine doses administered\n34**\n*\n•The VSD has not detected a statistical signal for myocarditis/pericarditis following \nthe 2024 -2025 COVID -19 vaccine to dateVaccine DosesCases in \nRisk \nInterval\n(Days 1 -21)Cases in \nComparison \nInterval\n(Days 22 -42)Adjusted Rate Ratio1 \n(95% Confidence Interval)\nPfizer 530,095 5 5 0.61 (0.11 – 2.88)\nModerna 35,194 0 0 n/a\nNovavax 1,576 0 0 n/a\n351 Adjusted for outcome calendar date, age group, sex, race/ethnicity, VSD site\nSource: CDC Immunization Safety Office, unpublished data through March 22, 2025 Myocarditis/pericarditis concurrent comparator analysis in \nVaccine Safety Datalink (VSD) after COVID -19 vaccine doses \namong people ages 12 -39 years, 2024 -2025\nVaccine Adverse Event Reporting System (VAERS) reports of \nmyocarditis within 7 days of COVID -19 vaccination  among \npeople ages 12 -39 years , 2024 -2025\n•The reporting rates are similar to the expected \nbackground rates of <2 cases per million dosesAge group \n(years)Verified casesReporting rate per \nmillion doses\n12-17 3 0.74\n18-29 0 0\n30-39 1 0.14\nSource: CDC Immunization Safety Office, unpublished data  through March 22, 2025  36\nMOVING Study: Outcomes after myocarditis following COVID -19 vaccine: \nCardiologist/healthcare provider assessment of recovery in persons ages 12 –29 years \nat least 90 days since onset of myocarditis after COVID -19 vaccination, 2021 -2022\n•81% (320/393) of \npatients were \nconsidered fully or \nprobably recovered by \ntheir cardiologist or \nother healthcare \nprovider\nKracalik  I, Oster ME, Broder KR et al. Outcomes at least 90 days since onset of myocarditis after mRNA COVID -19 vaccination in adolescen ts and young adults in the USA: a follow -up \nsurveillance study. Lancet Child & Adolescent Health, 2022. \nMOVING: Myocarditis Outcomes after COVID -19 Vaccine INvestiGation 371%16% 15%66%\n0%10%20%30%40%50%60%70%80%90%100%\nSame cardiac status\nas initial diagnosisImproved but not\n fully recoveredProbaby fully recovered\nbut awaiting infoFully recoveredPercent of respondents\nProvider -reported recovery status from myocarditis after mRNA COVID -19 vaccination\nMOVING* study: Outcomes after myocarditis following COVID -19 vaccine: Patient -\nreported assessment of recovery in persons ages 12 –29 years at least 90 days since \nonset of myocarditis after COVID -19 vaccination, 2021 -2022 \n•50% (178/357) of \npatients self -report \nat least 1 lingering \nsymptom at 3 \nmonths\n*MOVING: Myocarditis Outcomes after COVID -19 Vaccine INvestiGation\nKracalik  I, Oster ME, Broder KR et al. Outcomes at least 90 days since onset of myocarditis after mRNA COVID -19 vaccination in adolescen ts and young adults in the USA: a follow -up \nsurveillance study. Lancet Child & Adolescent Health, 2022. 38\nComposite outcome 1: rehospitalization for myopericarditis, cardiovascular event, or death from any cause.\nComposite outcome 2: rehospitalization for myopericarditis, cardiovascular event, hospitalization for any cause (>1 night sta y), or death \nfrom any cause.Comparison of myocarditis attributed to COVID -19 mRNA \nvaccination, SARS -CoV-2 infection or conventional \netiologies, 2020 -2022\nSemenzato  L, Le Vu S, Botton  J et al. Long -term prognosis of patients with myocarditis attributed to COVID -19 mRNA vaccination, SARS -CoV-2 infection, or con ventional etiologies. JAMA. \n2024 . https://jamanetwork.com/journals/jama/fullarticle/2822933  39\nSummary: myocarditis after COVID -19 vaccine\n•An increased risk of myocarditis following COVID -19 vaccines was \nobserved during 2020 -2022 following the primary series and first \nbooster doses\n•No increased risk was observed in VSD and VAERS with the 2022 -2023 \nand 2023 -2024 vaccines or the 2024 -25 vaccine to date\n•Acute clinical picture following myocarditis after COVID -19 vaccine \ntends to resolve quickly\n•Post -COVID -19 vaccine myocarditis associated with less severe \ncardiovascular events than post -COVID -19 myocarditis and \nconventional myocarditis \nVSD: Vaccine Safety Datalink | VAERS: Vaccine Adverse Event Reporting System 40\nRisk-based v. universal vaccine \nrecommendations and vaccine coverage \nInfluenza vaccination coverage among adults 18 -64 years with and \nwithout high -risk medical conditions, 2008 –09 through 2015 –16 \ninfluenza seasons, Behavioral Risk Factor Surveillance System\nVertical line denotes timing of universal influenza vaccination recommendation\nSelected high risk conditions include asthma, diabetes or heart disease (before the 2013 -14 season) or asthma, diabetes, heart d isease, chronic obstructive pulmonary disease or cancers \nother than skin cancer (2013 -14 season through present)\nSource: CDC Immunization Services Division, unpublished0102030405060708090100\n2008-09 2009-10 2010-11 2011-12 2012-13 2013-14 2014-15 2015-16Percent vaccinated\nInfluenza season18-49 with high risk conditions 18-49 without high risk conditions\n50-64 with high risk conditions 50-64 without high risk conditions\n42\nVaccination coverage: \nrisk-based vs. universal recommendations\n•Influenza vaccination coverage among adults with high -risk conditions increased \nslightly after the universal recommendation in the 2010 -11 season, but it was \nalready trending upward and plateaued shortly after the change in \nrecommendation.\n•Hepatitis B vaccination coverage among adults with risk factors remained below \npre-pandemic coverage after the universal recommendation in 2022.\n•Coverage among adults universally recommended for zoster vaccination was \napproaching pneumococcal vaccination coverage among high -risk adults by 2023, \ndespite longstanding pneumococcal vaccination recommendations for high -risk \nadults.\n•It is unclear how a change from a universal to risk -based recommendations may \nimpact COVID -19 vaccine coverage\n43 Source: CDC Immunization Services Division, unpublished data \nParental vaccine confidence\nCOVID -19 vaccination coverage among children 6 months –\n17 years, United States, 2023 -2024 through 2024 -2025\nCurrent season week ending date refers to the 2024 -2025 season only. For the 2023 -2024 season, the corresponding week is represe nted \nData source: National immunization survey – Flu https://www.cdc.gov/covidvaxview/weekly -dashboard/child -coverage -vaccination.html  \nAccessed April 7, 2025  45▪As of March 22, 2025, 12.8% of children 6 months -17 years reported having received the 2024─25 COVID -19 vaccine.\n\n66\n61\n48\n38\n35\n35\n33\n24\n2221\n27\n27\n17\n29\n32\n30\n21\n149\n9\n17\n17\n21\n21\n21\n20\n184\n4\n9\n29\n15\n12\n17\n35\n46\n0 25 50 75 100Get child vaccinated for COVID -19Have child mask with increased illness in communityTalk to child's doctor about prevention optionsDo my own research on prevention optionsLimit child's contact with others with increased illness in\ncommunityGet child vaccinated for fluGive child vitamins or supplementsFeed child healthy foodsHave child wash hands more\nWeighted %Very likely Somewhat likely A little likely Not likely\"How likely are you to take the following actions to help prevent your child \nfrom getting sick from a respiratory illness?\" Results Among Parents of Child \nAges 0 –17Years, Omnibus Surveys, November 7 —29, 2024 (N=1,141)\nOmnibus Surveys: Data for this analysis were collected through the Ipsos KnowledgePanel and NORC AmeriSpeak Omnibus Surveys, which use probability -based panels to \nsurvey a nationally representative sample of U.S. adults ages 18 years and older. CDC fields questions about vaccination status,  intent, knowledge, attitudes, beliefs, and \nbehaviors on each survey for 2 waves each month, for a combined sample size of ~4,000 respondents. These slides present resul ts from November (N=4,240). Data were \nweighted to represent the non -institutionalized U.S. population and mitigate possible non -response bias. All responses are self -reported. 46\n26 60 15 Safety (N=956)More confident now About the same confidence now Less confident now\n24 61 15\n0 25 50 75 100Effectiveness (N=948)\nWeighted %More confident now About the same confidence now Less confident now\"Are you more or less confident in the safety/effectiveness of COVID -19 vaccines for children now\ncompared to when they first came out?\" Results Among Parents of Child Ages 0 –17 Years Who Received \nat Least 1 Dose of aCOVID -19 Vaccine , Omnibus Surveys, December 5 , 2024–January 27, 2025\n47Omnibus Surveys: Data for this analysis were collected through the Ipsos KnowledgePanel and NORC AmeriSpeak Omnibus Surveys, which use probability -based panels to survey \na nationally representative sample of U.S. adults ages 18 years and older. CDC fields questions about vaccination status, int ent, knowledge, attitudes, beliefs, and behaviors on \neach survey for 2 waves each month, for a combined sample size of ~4,000 respondents. These slides present results from December  2024 & January 2025 (N=8,536). Data were \nweighted to represent the non -institutionalized U.S. population and mitigate possible non -response bias. All responses are self -reported.\n\"Are you more or less confident in the safety/effectiveness of COVID -19 vaccines for children now\ncompared to when they first came out?\" Results Among Parents of Child Ages 0 –17Years Who Have \nNever Received a COVID -19 Vaccine , Omnibus Surveys, December 5 , 2024 —January 27, 2025\n48Omnibus Surveys: Data for this analysis were collected through the Ipsos KnowledgePanel  and NORC AmeriSpeak  Omnibus Surveys, which use probability -based panels to survey a nationally representative sample of \nU.S. adults ages 18 years and older. CDC fields questions about vaccination status, intent, knowledge, attitudes, beliefs, an d behaviors on each survey for 2 waves each month, for a combined sample size of ~4,000 \nrespondents. These slides present results from December 2024 & January 2025 (N=8,536). Data were weighted to represent the no n-institutionalized U.S. population and mitigate possible non -response bias. All \nresponses are self -reported.6 49 45 Safety (N=1,308)More confident now About the same confidence now Less confident now\n4 51 45\n0 25 50 75 100Effectiveness (N=1,296)\nWeighted %More confident now About the same confidence now Less confident now\nChild’s 2024 -2025 COVID -19 Vaccination Status And Parental Intent to Get Their Child \nVaccinated, Results Among Parents of Child ren Ages 0 –17Years ,by Receipt of Prior COVID -19 \nVaccine(s), Omnibus Surveys, December 5 , 2024—January 27, 2025  (N=2,312)\nOmnibus Surveys: Data for this analysis were collected through the Ipsos KnowledgePanel  and NORC AmeriSpeak  Omnibus Surveys, which use probability -based panels to survey a nationally \nrepresentative sample of U.S. adults ages 18 years and older. CDC fields questions about vaccination status, intent, knowledg e, attitudes, beliefs, and behaviors on each survey for 2 waves each \nmonth, for a combined sample size of ~4,000 respondents. These slides present results from December 2024 & January 2025 (N=8, 536). Data were weighted to represent the non -institutionalized \nU.S. population and mitigate possible non -response bias. All responses are self -reported.4911 4 8 18 17 42\n26 8\n215\n323\n1518\n1611\n65\n0 25 50 75 100All parents (N=2,307)\nChild did NOT have 1+ doses (N=1,334)Child had 1+ doses (N=962)\nWeighted %Child received a COVID -19 vaccine since August 22, 2024 Definitely will get child vaccinated Probably will\nNot sure Probably will not Definitely will not\n43%\n31%\n30%\n13%\n12%\n4%\n8%\n0%\n3%\n1%\n25%\n0 20 40 60 80 100Concerned about safety\nConcerned about effectiveness\nConcerned about bad reaction\nNot/no longer a requirement\nNo recommendation from\nprovider\nHaven't had time\nChild has antibodies from\nrecent infection\nChild received enough doses *\nWorried about related cost\nDo not know where to get it\nNone of the above\nWeighted % (95% confidence interval)Child never vaccinated against COVID -19 (N=1,323)\n18%\n11%\n4%\n18%\n12%\n16%\n7%\n15%\n4%\n3%\n29%\n0 20 40 60 80 100\nWeighted % (95% confidence interval)Child received ≥1dose COVID -19 vaccine (N=695)Reasons for Not Getting Child a 2024 -2025 COVID -19 Vaccine , Among \nParents of Child Ages 0 –17, by Receipt of Prior COVID -19 Vaccine(s), \nOmnibus Surveys, December 5, 2024 —January 27, 2025\n*Option \"Child received enough doses\" only offered to parents of children  who have received at least one dose of any COVID -19 vaccine .\nOmnibus Surveys: Data for this analysis were collected through the Ipsos KnowledgePanel  and NORC AmeriSpeak  Omnibus Surveys, which use probability -based panels to survey a nationally \nrepresentative sample of U.S. adults ages 18 years and older. CDC fields questions about vaccination status, intent, knowledg e, attitudes, beliefs, and behaviors on each survey for 2 waves each \nmonth, for a combined sample size of ~4,000 respondents. These slides present results from December 2024 & January 2025 (N=8, 536). Data were weighted to represent the non -institutionalized \nU.S. population and mitigate possible non -response bias. All responses are self -reported. 50\nRecommendations in other countries \nSummary of international COVID -19 booster* recommendations\nUK1Canada2Australia3WHO US\nOlder adults ≥65 years: 12 months\n≥75 years and long -term \ncare facility residents: 6 \nmonths≥80 years and long -term care \nfacility residents: 6 months\n65-79 years: 12 months; may \nreceive every 6 months≥75 years: 6 months \n≥65 years: 12 months , may \nreceive every 6 monthsCountry dependent, often ≥75 or \n≥80 years: 6–12-month interval\nCountry dependent, often 50 or \n60 years : 12-month interval≥65 years: 6 months\nAdults (routine) Not recommended May receive every 12 months May receive every 12 \nmonthsNot routinely recommended\nPregnant adults and adolescents: \ndose in each pregnancy***12 months\nHigh -risk adults** 12 months 12 months May receive every 12 \nmonths12 months 12 months\nImmunocompromised \nadults6 months 6 months 12 months, may receive \nevery 6 months6-12 months 6 months, plus may \nreceive additional doses \nat 2-month intervals\nChildren (routine) Not recommended May receive every 12 months Not recommended Not routinely recommended 12 months\nHigh -risk children** 12 months 12 months Not recommended Not routinely recommended 12 months\nImmunocompromised \nchildren6 months 6 months Under 5 years: not \nrecommended\n5-17 years: May receive \nevery 12 months6-12 months 6 months, plus may \nreceive additional doses \nat 2-month intervals\n1 https://assets.publishing.service.gov.uk/media/66e7fbf624c4f1826d81bb32/Greenbook -chapter -14a-20240916.pdf  2 https://www.canada.ca/en/public -health/services/publications/vaccines -\nimmunization/national -advisory -committee -immunization -summary -guidance -covid -19-vaccines -2025 -summer -2026.html  3 https://www.health.gov.au/our -work/covid -19-vaccines/getting -your -\nvaccination/booster -doses  \n* Booster refers to people who have already completed an initial series. For people who are unvaccinated, more doses may be n eeded than are shown in this table\n** Adults and children at increased risk of SARS -CoV-2 exposure or severe COVID -19 disease. \n*** Ideally during in the second trimester or at any opportunity\nItalics indicate discretionary/shared clinical decision -making recommendations \n52\nUK1Canada2Australia3WHO US\nOlder adults ≥65 years: 12 months\n≥75 years and long -term \ncare facility residents: 6 \nmonths≥80 years and long -term care \nfacility residents: 6 months\n65-79 years: 12 months; may \nreceive every 6 months≥75 years: 6 months \n≥65 years: 12 months , may \nreceive every 6 monthsCountry dependent, often ≥75 or \n≥80 years: 6–12-month interval\nCountry dependent, often 50 or \n60 years : 12-month interval≥65 years: 6 months\nAdults (routine) Not recommended May receive every 12 months May receive every 12 \nmonthsNot routinely recommended\nPregnant adults and adolescents: \ndose in each pregnancy***12 months\nHigh -risk adults** 12 months 12 months May receive every 12 \nmonths12 months 12 months\nImmunocompromised \nadults6 months 6 months 12 months, may receive \nevery 6 months6-12 months 6 months, plus may \nreceive additional doses \nat 2-month intervals\nChildren (routine) Not recommended May receive every 12 months Not recommended Not routinely recommended 12 months\nHigh -risk children** 12 months 12 months Not recommended Not routinely recommended 12 months\nImmunocompromised \nchildren6 months 6 months Under 5 years: not \nrecommended\n5-17 years: May receive \nevery 12 months6-12 months 6 months, plus may \nreceive additional doses \nat 2-month intervalsSummary of international COVID -19 booster* recommendations\n1 https://assets.publishing.service.gov.uk/media/66e7fbf624c4f1826d81bb32/Greenbook -chapter -14a-20240916.pdf  2 https://www.canada.ca/en/public -health/services/publications/vaccines -\nimmunization/national -advisory -committee -immunization -summary -guidance -covid -19-vaccines -2025 -summer -2026.html  3 https://www.health.gov.au/our -work/covid -19-vaccines/getting -your -\nvaccination/booster -doses  \n* Booster refers to people who have already completed an initial series. For people who are unvaccinated, more doses may be n eeded than are shown on this table\n** Adults and children at increased risk of SARS -CoV-2 exposure or severe COVID -19 disease. \n*** Ideally during in the second trimester or at any opportunity\nItalics indicate discretionary/shared clinical decision -making recommendations \n53\nUK1Canada2Australia3WHO US\nOlder adults ≥65 years: 12 months\n≥75 years and long -term \ncare facility residents: 6 \nmonths≥80 years and long -term care \nfacility residents: 6 months\n65-79 years: 12 months; may \nreceive every 6 months≥75 years: 6 months \n≥65 years: 12 months , may \nreceive every 6 monthsCountry dependent, often ≥75 or \n≥80 years: 6–12-month interval\nCountry dependent, often 50 or \n60 years : 12-month interval≥65 years: 6 months\nAdults (routine) Not recommended May receive every 12 months May receive every 12 \nmonthsNot routinely recommended\nPregnant adults and adolescents: \ndose in each pregnancy***12 months\nHigh -risk adults** 12 months 12 months May receive every 12 \nmonths12 months 12 months\nImmunocompromised \nadults6 months 6 months 12 months, may receive \nevery 6 months6-12 months 6 months, plus may \nreceive additional doses \nat 2-month intervals\nChildren (routine) Not recommended May receive every 12 months Not recommended Not routinely recommended 12 months\nHigh -risk children** 12 months 12 months Not recommended Not routinely recommended 12 months\nImmunocompromised \nchildren6 months 6 months Under 5 years: not \nrecommended\n5-17 years: May receive \nevery 12 months6-12 months 6 months, plus may \nreceive additional doses \nat 2-month intervalsSummary of international COVID -19 booster* recommendations\n1 https://assets.publishing.service.gov.uk/media/66e7fbf624c4f1826d81bb32/Greenbook -chapter -14a-20240916.pdf  2 https://www.canada.ca/en/public -health/services/publications/vaccines -\nimmunization/national -advisory -committee -immunization -summary -guidance -covid -19-vaccines -2025 -summer -2026.html  3 https://www.health.gov.au/our -work/covid -19-vaccines/getting -your -\nvaccination/booster -doses  \n* Booster refers to people who have already completed an initial series. For people who are unvaccinated, more doses may be n eeded than are shown on this table\n** Adults and children  at increased risk of SARS -CoV-2 exposure or severe COVID -19 disease. \n*** Ideally during in the second trimester or at any opportunity\nItalics indicate discretionary/shared clinical decision -making recommendations \n54\nUK1Canada2Australia3WHO US\nOlder adults ≥65 years: 12 months\n≥75 years and long -term \ncare facility residents: 6 \nmonths≥80 years and long -term care \nfacility residents: 6 months\n65-79 years: 12 months; may \nreceive every 6 months≥75 years: 6 months \n≥65 years: 12 months , may \nreceive every 6 monthsCountry dependent, often ≥75 or \n≥80 years: 6–12-month interval\nCountry dependent, often 50 or \n60 years : 12-month interval≥65 years: 6 months\nAdults (routine) Not recommended May receive every 12 months May receive every 12 \nmonthsNot routinely recommended\nPregnant adults and adolescents: \ndose in each pregnancy***12 months\nHigh -risk adults** 12 months 12 months May receive every 12 \nmonths12 months 12 months\nImmunocompromised \nadults6 months 6 months 12 months, may receive \nevery 6 months6-12 months 6 months, plus may \nreceive additional doses \nat 2-month intervals\nChildren (routine) Not recommended May receive every 12 months Not recommended Not routinely recommended 12 months\nHigh -risk children** 12 months 12 months Not recommended Not routinely recommended 12 months\nImmunocompromised \nchildren6 months 6 months Under 5 years: not \nrecommended\n5-17 years: May receive \nevery 12 months6-12 months 6 months, plus may \nreceive additional doses \nat 2-month intervalsSummary of international COVID -19 booster* recommendations\n1 https://assets.publishing.service.gov.uk/media/66e7fbf624c4f1826d81bb32/Greenbook -chapter -14a-20240916.pdf  2 https://www.canada.ca/en/public -health/services/publications/vaccines -\nimmunization/national -advisory -committee -immunization -summary -guidance -covid -19-vaccines -2025 -summer -2026.html  3 https://www.health.gov.au/our -work/covid -19-vaccines/getting -your -\nvaccination/booster -doses  \n* Booster refers to people who have already completed an initial series. For people who are unvaccinated, more doses may be n eeded than are shown on this table\n** Adults and children  at increased risk of SARS -CoV-2 exposure or severe COVID -19 disease. \n*** Ideally during in the second trimester or at any opportunity\nItalics indicate discretionary/shared clinical decision -making recommendations \n55\nUK1Canada2Australia3WHO US\nOlder adults ≥65 years: 12 months\n≥75 years and long -term \ncare facility residents: 6 \nmonths≥80 years and long -term care \nfacility residents: 6 months\n65-79 years: 12 months; may \nreceive every 6 months≥75 years: 6 months \n≥65 years: 12 months , may \nreceive every 6 monthsCountry dependent, often ≥75 or \n≥80 years: 6–12-month interval\nCountry dependent, often 50 or \n60 years : 12-month interval≥65 years: 6 months\nAdults (routine) Not recommended May receive every 12 months May receive every 12 \nmonthsNot routinely recommended\nPregnant adults and adolescents: \ndose in each pregnancy***12 months\nHigh -risk adults** 12 months 12 months May receive every 12 \nmonths12 months 12 months\nImmunocompromised \nadults6 months 6 months 12 months, may receive \nevery 6 months6-12 months 6 months, plus may \nreceive additional doses \nat 2-month intervals\nChildren (routine) Not recommended May receive every 12 months Not recommended Not routinely recommended 12 months\nHigh -risk children** 12 months 12 months Not recommended Not routinely recommended 12 months\nImmunocompromised \nchildren6 months 6 months Under 5 years: not \nrecommended\n5-17 years: May receive \nevery 12 months6-12 months 6 months, plus may \nreceive additional doses \nat 2-month intervalsSummary of international COVID -19 booster* recommendations\n1 https://assets.publishing.service.gov.uk/media/66e7fbf624c4f1826d81bb32/Greenbook -chapter -14a-20240916.pdf  2 https://www.canada.ca/en/public -health/services/publications/vaccines -\nimmunization/national -advisory -committee -immunization -summary -guidance -covid -19-vaccines -2025 -summer -2026.html  3 https://www.health.gov.au/our -work/covid -19-vaccines/getting -your -\nvaccination/booster -doses\n* Booster refers to people who have already completed an initial series. For people who are unvaccinated, more doses may be n eeded than are shown on this table\n** Adults and children at increased risk of SARS -CoV-2 exposure or severe COVID -19 disease. \n*** Ideally during in the second trimester or at any opportunity\nItalics indicate discretionary/shared clinical decision -making recommendations \n56\nUK1Canada2Australia3WHO US\nOlder adults ≥65 years: 12 months\n≥75 years and long -term \ncare facility residents: 6 \nmonths≥80 years and long -term care \nfacility residents: 6 months\n65-79 years: 12 months; may \nreceive every 6 months≥75 years: 6 months \n≥65 years: 12 months , may \nreceive every 6 monthsCountry dependent, often ≥75 or \n≥80 years: 6–12-month interval\nCountry dependent, often 50 or \n60 years : 12-month interval≥65 years: 6 months\nAdults (routine) Not recommended May receive every 12 months May receive every 12 \nmonthsNot routinely recommended\nPregnant adults and adolescents: \ndose in each pregnancy***12 months\nHigh -risk adults** 12 months 12 months May receive every 12 \nmonths12 months 12 months\nImmunocompromised \nadults6 months 6 months 12 months, may receive \nevery 6 months6-12 months 6 months, plus may \nreceive additional doses \nat 2-month intervals\nChildren (routine) Not recommended May receive every 12 months Not recommended Not routinely recommended 12 months\nHigh -risk children** 12 months 12 months Not recommended Not routinely recommended 12 months\nImmunocompromised \nchildren6 months 6 months Under 5 years: not \nrecommended\n5-17 years: May receive \nevery 12 months6-12 months 6 months, plus may \nreceive additional doses \nat 2-month intervalsSummary of international COVID -19 booster* recommendations\n1 https://assets.publishing.service.gov.uk/media/66e7fbf624c4f1826d81bb32/Greenbook -chapter -14a-20240916.pdf  2 https://www.canada.ca/en/public -health/services/publications/vaccines -\nimmunization/national -advisory -committee -immunization -summary -guidance -covid -19-vaccines -2025 -summer -2026.html  3 https://www.health.gov.au/our -work/covid -19-vaccines/getting -your -\nvaccination/booster -doses  \n* Booster refers to people who have already completed an initial series. For people who are unvaccinated, more doses may be n eeded than are shown on this table\n** Adults and children at  increased risk of SARS -CoV-2 exposure or severe COVID -19 disease. \n*** Ideally during in the second trimester or at any opportunity\nItalics indicate discretionary/shared clinical decision -making recommendations \n57\nUK1Canada2Australia3WHO US\nOlder adults ≥65 years: 12 months\n≥75 years and long -term \ncare facility residents: 6 \nmonths≥80 years and long -term care \nfacility residents: 6 months\n65-79 years: 12 months; may \nreceive every 6 months≥75 years: 6 months \n≥65 years: 12 months , may \nreceive every 6 monthsCountry dependent, often ≥75 or \n≥80 years: 6–12-month interval\nCountry dependent, often 50 or \n60 years : 12-month interval≥65 years: 6 months\nAdults (routine) Not recommended May receive every 12 months May receive every 12 \nmonthsNot routinely recommended\nPregnant adults and adolescents: \ndose in each pregnancy***12 months\nHigh -risk adults** 12 months 12 months May receive every 12 \nmonths12 months 12 months\nImmunocompromised \nadults6 months 6 months 12 months, may receive \nevery 6 months6-12 months 6 months, plus may \nreceive additional doses \nat 2-month intervals\nChildren (routine) Not recommended May receive every 12 months Not recommended Not routinely recommended 12 months\nHigh -risk children** 12 months 12 months Not recommended Not routinely recommended 12 months\nImmunocompromised \nchildren6 months 6 months Under 5 years: not \nrecommended\n5-17 years: May receive \nevery 12 months6-12 months 6 months, plus may \nreceive additional doses \nat 2-month intervalsSummary of international COVID -19 booster* recommendations\n1 https://assets.publishing.service.gov.uk/media/66e7fbf624c4f1826d81bb32/Greenbook -chapter -14a-20240916.pdf  2 https://www.canada.ca/en/public -health/services/publications/vaccines -\nimmunization/national -advisory -committee -immunization -summary -guidance -covid -19-vaccines -2025 -summer -2026.html  3 https://www.health.gov.au/our -work/covid -19-vaccines/getting -your -\nvaccination/booster -doses\n* Booster refers to people who have already completed an initial series. For people who are unvaccinated, more doses may be n eeded than are shown on this table\n** Adults and children  at increased risk of SARS -CoV-2 exposure or severe COVID -19 disease. \n*** Ideally during in the second trimester or at any opportunity\nItalics indicate discretionary/shared clinical decision -making recommendations \n58\nWork Group Interpretations\n•When initially presented with 2025 –2026 COVID -19 vaccine policy options \nin November 2024, the Work Group appreciated pros and cons of both \nrisk-based and universal vaccine recommendations.\n•At that time, there was not yet a consensus on what the recommendation \nfor the 2025 –2026 COVID -19 vaccine should be.\n•The Work Group requested additional information to help inform the \ndecision -making process on risk -factors for severe COVID -19, transmission \nand immunity, vaccine implementation and access, and cost -effectiveness. Initial Work Group interpretations\n60\nWhen polled on February 13, 2025, the majority of the work group \nsupported a non -universal (risk -based) recommendation for 2025 –2026 \nCOVID -19 vaccination\n14%19%67%\n0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%Don't knowUniversal recommendation for \neveryone aged ≥6 months Non-universal recommendation\nPercent of work group2025 –2026 Vaccination Policy\n61\nWhen polled on February 13, 2025, the Work Group supported \nall non -universal policy options *\n86%93%79%\n0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%Allowance for anyone wanting protection\n from vaccinationCertain age groups (e.g., persons aged ≥65 years)Specific high-risk conditions and exposures\nPercent of COVID -19 vaccine Work Group members who selected a non -universal vaccine policy \nrecommendationGroups to be included in 2025 –2026 COVID -19 vaccine recommendation\n* More than one response option could be selected. 62\n•2024 -2025 COVID -19 vaccine effectiveness\n•Seroprevalence of SARS -CoV-2\n•Long COVID\n•COVID -19 vaccine coverage update\n•Multisystem Inflammatory Syndrome in Children (MIS -C)\n•Liaison feedback (see next slide)Additional data presented to the Work Group \n(March – April 2025)\n63\n•American Academy of Family Physicians (AAFP)\n•American Academy of Pediatrics (AAP)\n•Association of Immunization Managers (AIM)\n•American College of Physicians (ACP)\n•American Pharmacists Association ( APhA )\n•American College of Obstetricians and Gynecologists (ACOG)\n•Concerns were raised regarding implementation, communication, confidence in \nrecommendations and equitable access to vaccination with a potential risk -based \nrecommendation Liaison feedback on a potential risk -based recommendation \nobtained from the following organizations (March – April 2025)\n64\nWhen polled on April 3, 2025 , the majority of the work group continued \nto support a non -universal (risk -based) recommendation for 2025 –2026 \nCOVID -19 vaccination\n0%24%76%\n0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%Don't knowUniversal recommendation for \neveryone aged ≥6 months Non-universal recommendation\nPercent of work group2025 –2026 Vaccination Policy\n65\nWhen polled on April 3, 2025, the Work Group continued to \nsupport all non -universal policy options* \n89%84%84%\n0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%Allowance for anyone wanting protection\n from vaccinationCertain age groups (e.g., persons aged ≥65 years)Specific high-risk conditions and exposures\nPercent of COVID -19 vaccine Work Group members who selected a non -universal vaccine policy \nrecommendationGroups to be included in 2025 –2026 COVID -19 vaccine recommendation\n* More than one response option could be selected. 66\nRisk for COVID -19–associated hospitalization is increased \namong community -dwelling adults ages ≥18 years with \nunderlying medical conditions.\nAbbreviations: RR, rate ratio; CI, confidence interval; COPD, chronic obstructive pulmonary disease.\n* “None” refers to having none of the conditions examined in this analysis ( asthma, COPD, diabetes, chronic kidney disease, coronary artery disease, stroke, severe obesity, and current smoking).\n** “Any condition” refers to having at least 1 of these conditions. Notes: Non -severe obesity is defined as BMI 30 –39kg/m². Severe obesity is defined as BMI ≥40kg/m². “Any condition” includes \nasthma, COPD, diabetes, chronic kidney disease, coronary artery disease, stroke, severe obesity, and current smoking. Rate ra tios were estimated using multivariable Poisson models adjusted for sex, \nand race/ethnicity. “Smoker (current)” Includes people who quit smoking within the past 12 months. Data are limited to hospit alizations where COVID -19 is the likely reason for admission. 67Patterned bars indicate CIs that include 1.0.\n0.1110100\nNone* Any\ncondition**Asthma COPD Chronic\nkidney\ndiseaseCoronary\nartery\ndiseaseDiabetes Stroke\n(history of)Obesity\n(non-severe)Obesity\n(severe)Smoker\n(current)Adjusted RR (log scale)Adjusted Rate Ratios for COVID -19–associated Hospitalizations among Community -Dwelling Adults Ages ≥18 Years,\nby Age Group — October 2022 –September 2023\n18–49 50–64 65–74≥75\n•General thoughts on universal vs. risk -based recommendation for COVID -19 vaccination\n•Are there groups that clearly should not be recommended for vaccination with the 2025 –2026 \nvaccine ​?\n•What data would be helpful in your decision making?\n•Is it still helpful to have a risk -based recommendation if most of thepopulation (>74%) is \nconsidered “at risk”?\n•Should people at higher risk of infection and transmission (e.g., healthcare workers) be included in \na risk -based recommendations? \n•Will stable (i.e., universal) recommendations increase  uptake with time?\n•Concerns about implementation challenges with risk -based recommendations?\n•Any potential unintended implications or consequences of a recommendation change?\n•Are there key decision points we have not captured here?Discussion\n68\nAcknowledgements\n•Lauren Roper\n•Farida Ahmad\n•Carla Black\n•Kayla Calhoun\n•Angela Campbell \n•Mary Chamberland\n•Nicole Dowling\n•Jonathan Duffy\n•Monica Godfrey\n•Susan Goldstein\n•Fiona Havers\n•Jefferson Jones•Ruth Link -Gelles\n•Meredith McMorrow\n•Sarah Meyer\n•Pedro Moro\n•Danielle Moulia\n•Matthew Oster\n•Hilda Razzaghi\n•Sharon Saydah\n•Sierra Scarbrough\n•Zachary Schneider\n•Benjamin Silk\n•Christopher Taylor•Natalie Thornburg\n•Evelyn Twentyman\n•Eric Weintraub\n•Anna Yousef\n•Coronavirus and other Respiratory \nViruses Division\n•COVID -NET Team\n•Immunization Safety Office\n•Immunization Services Division\n•National Center for Immunization and \nRespiratory Diseases\n69", "summary": "Use of 2025 –2026 COVID -19 Vaccines: Work Group Considerations Lakshmi Panagiotakopoulos, MD, MPH Advisory Committee on Immunization Practices April 15, 2025National Center for Immunization and Respiratory Diseases   •Current recommendations for 2024 –2025 COVID -19 vaccines •Policy options for 2025 –2026 COVID -19 vaccine recommendations •Supporting data and Work Group interpretations •Discussion questions for committee Overview 2 COVID -19 vaccine: ACIP Meeting Schedule October  2024April…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/05-Panagiotakopoulos-COVID-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 69}
{"title": "01 Kobayashi Pneumococcal 508", "content": "Pneumococcal Vaccines Work Group\nApril 2025, ACIP meeting\nApril 15, 2025\nMiwako Kobayashi\nNational Center for Immunization and Respiratory Diseases\n1U.S. Centers for Disease Control and Prevention\nPneumococcal Vaccines Work Group\nACIP Members\n•Jamie Loehr (Chair)\n•Mini Kamboj\n•George Kuchel\n•Robert Schechter\n  \nEx Officio Members\n•Tina Mongeau   (FDA)\n•Nick Geagan       (FDA)\n•Uzo Chukwuma (IHS)\n•Mamodikoe Makhene (NIH, primary)\n•Meenu Upadhyay (NIH, alternate)\n•Risa Claytor                (HRSA)\nLiaison Representatives\n•  Lynn Fisher                (AAFP)\n•  Monica Ardura        (AAP/COID)•Jason Goldman         (ACP)\n•Saba Hasan                (ACP , alternate)\n•James McAuley         (IDSA)\n•Eva Wong                    (NACI)\n•Robert Hopkins         (NFID, primary)\n•William Schaffner     (NFID, alternate)\n•Michelle Floris -Moore   (NMA)\n•Mary Hayney             ( APhA )\nConsultants\n•Monica Farley            (Emory)\n•Keith Klugman          (Gates Foundation)\n•Kathy Poehling         (Wake Forest)\n•Arthur Reingold        (UC Berkley)\n•Lorry Rubin                 (CCMC)\n•Richard Zimmerman (U. of Pittsburgh)\nCDC Contributors\nArctic Investigations Program\n•Heather Scobie\nCDC Lead\n•Miwako KobayashiDivision of Bacterial Diseases\n•Adam Cohen\n•Ryan Gierke             \n•Noele Nelson    \nImmunization Safety Office\n•Pedro Moro               \nImmunization Services Division\n•Nancy Wong\nPneumococcal Work Group Terms of Reference\n•Review evidence to inform use of new pneumococcal conjugate vaccines in \nU.S. adults and children\nACIP Work Groups | ACIP | CDC 4\nHistory of US Pneumococcal Vaccine Program, \n1984 –2024 \n1984PPSV23:  adults aged \n≥65 years and \nindividuals with \nunderlying conditions\n2000 2010 2019 2014 2012\nPCV7: Children PCV13:  Children \n(replaced PCV7)PCV13:  Adults with \nimmunocompromising \nconditionsPCV13:  All adults \naged ≥65PCV13 based on SCDM for all adults aged ≥65 years\nPCV=pneumococcal conjugate vaccine, PPSV23=23 -valent pneumococcal polysaccharide vaccine, SCDM=shared clinical decision -making2021/2022\nPCV15: Adults/childrenPCV20 : Adults2023\nPCV20:  \nChildren2024PCV21:  \nAdults\nCurrent gaps in pneumococcal vaccine \nrecommendations\n•Pregnant women\n-Currently no recommendation\n \nAdult Immunization Schedule by Medical Condition and Other Indication | Vaccines & Immunizations | CDC\n\nCurrent gaps in pneumococcal vaccine \nrecommendations\n•Hematopoietic Stem Cell Transplant (HSCT) recipients\n-Different vaccination schedule compared with other risk conditions (last updated \nin 2023)\n-No clinical guidance for PCV21 use\nPneumococcal Vaccine for Adults Aged ≥19 Years: Recommendations of the Advisory Committee on Immunization Practices, United S tates, 2023 | MMWR\nProposed work plan\n•Review of literature on pneumococcal vaccine use in pregnant women \nand HSCT recipients focusing on data on:\n-Pneumococcal disease incidence and serotype distribution\n-Vaccine efficacy, effectiveness, and impact\n-Immunogenicity\n-Safety\n•Plan to present summary of findings and proposed language for updated \nclinical guidance on pneumococcal vaccine use at the June 2025 ACIP \nmeeting\n8\nThank you!\nFor more information, contact CDC\n1-800- CDC- INFO (232 -4636)\nTTY:  1 -888- 232- 6348    cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the U. S. Centers for Disease Control and Prevention.\n9", "summary": "Pneumococcal Vaccines Work Group April 2025, ACIP meeting April 15, 2025 Miwako Kobayashi National Center for Immunization and Respiratory Diseases 1U.S. Centers for Disease Control and Prevention Pneumococcal Vaccines Work Group ACIP Members •Jamie Loehr (Chair) •Mini Kamboj •George Kuchel •Robert Schechter    Ex Officio Members •Tina Mongeau   (FDA) •Nick Geagan       (FDA) •Uzo Chukwuma (IHS) •Mamodikoe Makhene (NIH, primary) •Meenu Upadhyay (NIH, alternate) •Risa Claytor               …", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/01-Kobayashi-Pneumococcal-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 9}
{"title": "01 Brooks HPV 508", "content": "Introduction to the HPV Vaccines Work Group\nOliver Brooks, MD\nChair, HPV Vaccines Work Group\nAdvisory Committee on Immunization Practices\nApril 15, 2025\nNational Center for Immunization & Respiratory Diseases\n•HPV can cause cancer of the cervix, vagina, vulva, penis, anus, and oropharynx\n•HPV vaccination provides lasting protection against the HPV types that most \ncommonly cause cancer\n•In the 19 years since HPV vaccine licensure, we have seen:\n-High vaccine efficacy in clinical trials\n-High population impact in real -world settings\n-Strong herd effects of vaccination programsHPV vaccine is a critical public health tool\n2\n•An ACIP HPV Vaccines Work Group met previously for many years, but \nhad been inactive since 2019\n•Re-formed ACIP HPV Vaccines Work Group was announced during June \n2024 ACIP meeting and began meeting monthly in July 2024\n•First presentation by new Work Group during October 2024 ACIP meetingBackground\n3\n•Routine vaccination\n-Age 11 or 12 years \n-Can be started at age 9 years \n•Catch -up vaccination \n-Through age 26 years\n•Shared clinical decision -making \n-Age 27 –45 yearsCurrent HPV vaccination recommendations, \nUnited States\nRecommendations of the Centers for Disease Control and Prevention and the Advisory Committee on Immunization Practices \nhttps://www.cdc.gov/vaccines/hcp/acip -recs/vacc -specific/hpv.html  Number of doses\n2 doses  (0, 6 -12 months) \nif starting series before 15th birthday\n3 doses  (0,1-2, 6 months) \nif starting series on or after 15th birthday or if \nimmunocompromising condition\n4\n•Wording of the age for routine HPV vaccination\n-Some stakeholders interested in starting vaccination at age 9 years\n-Current ACIP recommendations are consistent with vaccination at age 9 years\n-Work Group is considering m odification of wording to “ HPV vaccination is routinely \nrecommended at age 9 to 12 years”  to allow more flexibility Work Group Terms of Reference\n5\n•Number of doses in the recommended HPV vaccination series\n-Accumulating evidence on efficacy of HPV vaccination with fewer doses\n-Work Group is reviewing data to inform policy for:\n•two doses for persons aged 15 years and older\n•one dose for persons aged 9 years and olderWork Group Terms of Reference\n6\n•2022: WHO recommended a 2 -dose schedule for ages 9 and older, with an option for a 1 -dose \nschedule in girls and boys aged 9 –20 years\n•Some of the first countries to change to a routine 1-dose recommendation\n–UK and Australia\n•Some countries did not change to a 1 -dose schedule, but changed from a 3-dose to a 2 -dose schedule \nfor persons ages >14 years\n–e.g., Netherlands and Sweden\n•1-dose recommendations  have been made  by regional advisory groups\n–PAHO in 2023 and AFRO in 2024\n•As of April 2025: in some age groups, 67 countries have adopted 1 -dose  and 77 countries have \nadopted 2 -dose HPV vaccination schedulesGlobal HPV vaccine policy recommendations\n7Pan American Health Organization (PAHO): https://www.paho.org/fr/node/92810  \nWHO African Region (AFRO): https://www.afro.who.int/news/africa -immunization -advisory -group -urges -single -dose -hpv -vaccine -adoption -advance -vaccination\n•Introduction to reduced number of HPV vaccine doses\n-Summary of evidence on 1 -dose HPV vaccination\n•Introduction to wording of age for routine HPV vaccination\n-Interest in vaccination at age 9 years\n•Systematic review and narrative summary of literature about HPV \nvaccination at ages 9 –10 years to increase coverageSummary of October 2024 presentation\n8\nToday’s agenda\nReduced number of doses for HPV vaccination: \nWork Group progress and literature updateDr. Carla DeSisto\nCDC/NCIRD\nKEN  SHE trial Dr. Ruanne  Barnabas\nHarvard University\nHPV vaccination coverage Ms. Cassandra Pingali\nCDC/NCIRD\nModeling of reduced number of doses for HPV \nvaccinationDr. Jane Kim\nHarvard University\nModified EtR: Wording of the age for routine HPV \nvaccinationDr. Ruth Stefanos\nCDC/NCIRD\nNext steps  and Work Group considerations Dr. Lauri Markowitz\nCDC/NCIRD\n9\nACIP HPV Vaccines Work Group\nACIP voting members\nOliver Brooks (chair)\nNoel Brewer \nSybil Cineas\nRobert Schechter\nCDC Co -Leads\nCarla DeSisto\nLauri MarkowitzLiaison members\nRobin O'Meara (AAFP)\nAngela Myers (AAP)\nLinda Eckert (ACOG)\nAlfonso Iorio  (ACP)\nJamilia Sherls (AIM)\nSandra Fryhofer (AMA)\nSean O'Leary (IDSA)\nNicole Forbes (NACI)\nKevin Ault (NFID)\nAlexandra Yonts (PIDS)\nNneka Holder (SAHM)\n10Ex-Officio members\nSixun Yang (FDA)\nAimée  R. Kreimer (NIH)\nEleanore Chuang (NIH)\nConsultant members\nDeana Baptiste (ACS)\nPeter Szilagyi\nRachel Winer\nElizabeth Moore (consumer rep)\nJulia Gargano (DVD)\nRuth Stefanos (DVD)\nVirginia Senkomago (DCPC)\nPatrick Clay (DSTDP)\nHarrell Chesson (DSTDP)\nShannon Stokley (ISD)\nCassandra Pingali (ISD)ACIP HPV Vaccines Work Group - CDC Staff\nElizabeth R. Unger (DHCPP)\nGitika Panicker (DHCPP)\nChristine Olson (ISO)\nJulianne Gee (ISO)\nHannah Rosenblum (ACIP Secretariat)\n11", "summary": "Introduction to the HPV Vaccines Work Group Oliver Brooks, MD Chair, HPV Vaccines Work Group Advisory Committee on Immunization Practices April 15, 2025 National Center for Immunization & Respiratory Diseases •HPV can cause cancer of the cervix, vagina, vulva, penis, anus, and oropharynx •HPV vaccination provides lasting protection against the HPV types that most  commonly cause cancer •In the 19 years since HPV vaccine licensure, we have seen: -High vaccine efficacy in clinical trials -High…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/01-Brooks-HPV-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 11}
{"title": "02 DeSisto HPV 508", "content": "Reduced number of doses for HPV vaccination series: \nWork Group progress and literature update\nCarla L. DeSisto, PhD, MPH\nCo-Lead, HPV Vaccines Work GroupNational Center for Immunization and Respiratory Diseases\nAdvisory Committee on Immunization Practices\nApril 15, 2025\n•PICO and outcomes\n•Introduction to systematic review\n•Updated data from studies of interest\n•Observational studies of HPV vaccine effectiveness\n•Outstanding questions for reduced  number of HPV vaccine dosesOutline\n2\nPICOs and outcomes\nPICO questions1 \nPolicy question Should 1 dose of HPV vaccine be used for \nprevention of HPV infection and HPV attributable \ndisease, instead of the currently recommended \nvaccination schedule? Should 2 doses of HPV vaccine be used \nfor prevention of HPV infection and \nHPV attributable disease, instead of the \ncurrently recommended vaccination \nschedule? \nPopulation Persons aged 9 –14 yrs\nExcept persons with \nimmunocompromising \nconditionsPersons aged 15 –X yrs2\nExcept persons with \nimmunocompromising \nconditionsPersons aged 15 –X yrs2\nExcept persons with immunocompromising \nconditions\nIntervention 1 dose of HPV vaccine 2 doses of HPV vaccine\nComparison \n(current \nrecommendation )2 doses for persons who \ninitiate at ages 9–14 yrs3 doses for persons who \ninitiate at age ≥15 yrs3 doses for persons who initiate at age \n≥15 yrs\n1We are not intending this to change the recommendation of shared clinical decision -making for persons aged 27 -45 years, \nalthough the number of recommended doses in this age group may change.\n2Upper age to be discussed by Work Group after we review data\nNote: We will review  data on 1 vs 2 doses in persons aged 15+, but are focusing PICOs on comparing to current recommendations4\nOutcomes\nOutcome Importance\nHPV -associated cancers Critical\nPre-cancers (CIN2+ or AIN2+) Critical\nSerious adverse events related to vaccination Critical\nIncident -persistent HPV infection Critical\nPrevalent HPV infection Important\nIncident HPV infection Important\nImmunogenicity Important\nAnogenital warts Important\nLow -grade histological abnormalities (CIN1 or AIN1) Important\nRecurrent respiratory papillomatosis Important\n5\nIntroduction to systematic review\n•Cochrane reviewed the global literature on HPV vaccination schedules \nwith reduced number of doses in 2022 \n-59 studies (73 publications) were included in review; 49 studies were later \nexcluded due to serious risk of bias\n•We are starting with Cochrane’s review but putting it into U.S. context\n-Only including studies of vaccines that are licensed in the United States\n-Using 18 publications from Cochrane’s systematic review\n•Updated Cochrane’s literature search for publications during 2022 –2024\n-Yielded 22 additional publications; 3 excluded due to serious risk of bias\n-37 total included publicationsSystematic review of the literature\n7\nIncluded studies in alphabetical order\n8Study name or first author Study design Population and age at vaccination Vaccine\nBatmunkh  2020 (Mongolia) Retrospective cohort Females, 11 -17y 4vHPV\nBerenson 2024 (USA) RCT Females, 15 -26y 9vHPV\nBornstein 2021 (global) RCT Girls and boys, 9 -14y 9vHPV\nCosta Rica Vaccine Trial (CVT) Post -hoc analysis of RCT Females,18 -25y 2vHPV\nCVT/PATRICIA Post -hoc analysis of 2 RCTs Females,15 -25y 2vHPV\nDoRIS  (Tanzania) RCT Females, 9 -14y 2vHPV and 9vHPV\nHariri 2018 (USA) Retrospective cohort Females, age NR 4vHPV\nHOPE (South Africa) Repeat cross -sectional Females, 15 -16y 2vHPV\nIARC -India Post -hoc analysis of RCT Females, 10 -18y 4vHPV\nJiamsiri  2024 (Thailand) Repeat cross -sectional Females, 13 -14y 2vHPV\nKEN SHE (Kenya) RCT Females,15 -20y 2vHPV and 9vHPV\nKlein 2024 (USA) Cohort Girls and boys, 9 -14y 9vHPV\nMoss 2024 (USA) Cohort Females, 15 -45y 9vHPV\nReyburn  2023 (Fiji) Retrospective cohort Females, 9 -12y 4vHPV\nWu 2025 (Sweden) Retrospective cohort Females, 10 -35y 4vHPV\nZeng 2023 (USA) Cohort Girls and boys, 9 -11y 9vHPV\nOutcome # of studies RCTs Post -hoc analysis of \nRCTsObservational \nstudies\nHPV -associated \ncancers1 IARC -India (15y; 0 cases)\nPre-cancers (CIN2+ \nor AIN2+)2 IARC -India (15y) Wu-Sweden (8 -12y)\nIncident -persistent \nHPV infection3 KEN SHE (4.5y) IARC -India (15y), \nCVT/PATRICIA (4y)\nSerious adverse \nevents related to \nvaccinationn/a - data to be summarized in narrative review\n9Critical outcomes: Studies contributing data and time \nsince vaccination\nOutcome # of \nstudiesRCTs Post -hoc \nanalysis of RCTsObservational studies\nPrevalent HPV infection 5 CVT (11y) Reyburn -Fiji (8y), Batmunkh -\nMongolia (6y), Jiamsiri -Thailand (4y), \nHOPE -South Africa (2y)\nIncident HPV infection 2 IARC -India (15y), \nCVT (11y)\nImmunogenicity 11 DoRIS -Tanzania (5y), \nKEN SHE (2y), \nBornstein -global (1y), \nBerenson -USA (1m)CVT (16y),    \nIARC -India (10y)Batmunkh -Mongolia (6y), \nJiamsiri -Thailand (4y), \nZeng -USA (6m),  Moss -USA (1m), \nKlein -USA (follow -up varied)\nAnogenital warts 2 Reyburn -Fiji (8y), \nHariri -USA (follow -up NR)\nLow -grade histological \nabnormalities (CIN1 or \nAIN1)1 IARC -India (15y)\nRecurrent respiratory \npapillomatosisn/a\n10Important outcomes: Studies contributing data and time since vaccination\nUpdated data from studies of interest\nTrial/country Evidence VaccineAge ( yrs) at \nvaccinationDescription\nCVT \nCosta RicaEfficacy/\nImmunogenicity2vHPV 18–25 Post -hoc analyses  \nOriginal trial: randomized to 3 doses or \ncontrol, but analyzed as 1 -, 2-, 3-dose groups\nIARC -India\nIndiaEfficacy/\nImmunogenicity4vHPV 10–18 Post -hoc analyses\nOriginal trial: randomized to 2 or 3 doses \nbut analyzed as 1 -, 2-, 3-dose groups\nKEN SHE\nKenyaEfficacy 2vHPV \n9vHPV15–20 Randomized trial  \n1 dose 2vHPV, 9vHPV or MCV\nDoRIS \nTanzaniaImmunogenicity 2vHPV \n9vHPV9–14 Randomized trial  \n1-, 2-, 3-dose groups\n122vHPV, Cervarix;  9vHPV, Gardasil 9; CVT, Costa Rica Vaccine Trial; IARC, International Agency for Research on CancerTrials with data on single -dose HPV vaccination \nconsidered by the World Health Organization in 2022\n•Women aged 18 –25 years were randomly assigned to receive 3 doses of \n2vHPV or hepatitis A vaccine\n•Some women did not receive all 3 doses due to pregnancy, colposcopy \nreferral, a medical condition, participant refusal, or missing a study visit\n-Reasons for receiving fewer doses were balanced within each dosage group \nbetween women receiving the HPV and control vaccines\n•Data evaluated as cohort study of women who received 1, 2, or 3 doses\n•We previously reviewed data on protection against prevalent infection \nand immunogenicity through 11 yearsCosta Rica Vaccine Trial (CVT)\n13\n•16 years after vaccination, HPV 16/18 seropositivity was very high (>98%)\n•During years 11 –16 after vaccination, small but statistically significant \ndeclines in antibodies observed in women who received 3 doses and 1 doseCosta Rica Vaccine Trial (CVT): 2024 update\n14 Porras et al 2024 https://academic.oup.com/jncimono/article/2024/67/329/7821493\n\n•Unmarried girls aged 10 –18 years were randomly assigned to receive \neither 2 or 3 doses of 4vHPV\n•A ministerial decree to halt vaccination in trials resulted in the creation of \ncohorts of women who received 1, 2, or 3 doses\n•Cervical screening with an HPV test was initiated at age 25 years for \nmarried participants\n-Positive screening → colposcopy; negative screening → repeat in 5 years\n•Age- and site -matched unvaccinated married women recruited as controls\n•We previously reviewed data on protection against persistent infection \nthrough 10 yearsIARC -India Trial\n15\n•Median follow -up time = 12 years; time since study began = 15 years\n-Currently aged 25 –33 years\n•VE against persistent HPV 16/18 infection by number of doses:\n-1 dose: 92.0% (95% CI: 87.0% –95.0%)\n-2 doses: 94.8% (95% CI: 90.0% –97.3%)\n-3 doses: 95.3% (95% CI: 90.9% –97.5%)\n•No CIN2+ associated with HPV 16/18 detected among vaccinated \nparticipants (compared with 8 among unvaccinated women)\n•No cases of invasive cervical cancer associated with HPV 16/18 in studyIARC -India Trial: 2024 update\n16 Malvi et al 2024 https://academic.oup.com/jncimono/article/2024/67/317/7821485  \n•Dose Reduction Immunobridging  & Safety Study \n•Girls aged 9 –14 years were randomly assigned to 1, 2, or 3 doses of either \n2vHPV or 9vHPV\n•All participants followed until month 36; 1 - and 2 -dose groups invited to \njoin long -term extension (through 9 years)\n•Objective was to demonstrate noninferiority: \n-HPV 16 and 18 antibody response after 1 vs 2 or 3 doses of same vaccine\n-HPV 16 and 18 GMCs: 1 dose in DoRIS  vs 1 dose in studies that evaluated efficacy \n•We previously reviewed data on immunogenicity (seropositivity and \nGMCs) and immunobridging  to KEN SHE through 2 yearsDoRIS  (Tanzania)\n17\n•Seropositivity:  \n-HPV 16: 100% seropositive in 1 -dose and 2 -dose arms\n-HPV 18: 93% seropositive in 1 -dose arm, 98% seropositive in 2 -dose arm\n-Non -inferiority of HPV 18 seropositivity was not metDoRIS : 2025 update (9vHPV results) – 5 years after \nvaccination\n18 Watson -Jones et al 2025 https://pubmed.ncbi.nlm.nih.gov/39890232/  \nDoRIS : 2025 update (9vHPV results) – 5 years after \nvaccination\n19\n•GMCs:\n-1-dose arm: plateaued at month 12, relatively constant through month 60\n-2-dose arm: declined after peak at month 7 \n-Lower in 1 -dose arm than in 2 -dose arm, as expected\nObservational studies of vaccine effectiveness \n•Most important sources of bias:\n-Differences between dose groups in risk of prevalent infection at time of vaccination \n-Differences between dose groups in risk of HPV acquisition during follow -up\n-Potential impact of interval between 1st and 2nd dose on vaccine effectiveness\n•Serious bias would likely result in lower effectiveness with fewer doses\n•Ways investigators attempt to control for biases:\n-Using buffer periods to exclude outcomes caused by prevalent infections at vaccination\n-Stratifying results for age at vaccination or restricting the population to younger ages \n-Adjusting for indicators of sexual activity and socio -demographic characteristics\n-Stratifying results for 2 doses by the interval between 1st and 2nd dose (e.g., <5 , ≥5m)Bias in observational studies of HPV vaccine \neffectiveness by number of doses\n21 Markowitz et al 2022 https://www.sciencedirect.com/science/article/pii/S0264410X22008349?via%3Dihub  \n•Cohort study of 2.2M females aged 10 –35, residents of Sweden 2006 –2022\n•Linked several registries, including vaccination and cervical screening\n•Exposure (time -varying): number of doses of 4vHPV \n•Outcome: CIN2+\n•Used Poisson models to estimate incidence rate ratios (IRR) vs. unvaccinated\n-Adjusted for age, calendar year, county of residence, maternal history of high -grade \ncervical lesions, mother’s country of birth, parental education, and household income\n-1 year buffer\n•Median years of follow -up (IQR): \n-Unvaccinated: 8.4 (2.3 –15.3); Vaccinated: 12.4 (8.7 –17.0)Wu-Sweden 2025: methods summary\n22\nWu-Sweden 2025: CIN2+ by age at vaccination\n23 Wu et al https://www.thelancet.com/journals/lanepe/article/PIIS2666 -7762(24)00347 -8/fulltext  \nOutstanding questions for reduced \nnumber of HPV vaccine doses \n▪Longer term efficacy and immunogenicity\n▪Protection at sites other than the cervix\n▪Efficacy and immunogenicity in males\n▪Efficacy and immunogenicity in immunocompromised persons\n▪Efficacy and immunogenicity in older age groupsOutstanding questions for reduced  number of  HPV vaccine doses\n25\n▪Longer term efficacy and immunogenicity\n➢Longest efficacy data: IARC -India (15 years)\n➢Longest immunogenicity data: Costa Rica Vaccine Trial (16 years)\n▪Protection at sites other than the cervix\n➢No data on protection at sites other than the cervix\n▪Efficacy and immunogenicity in males\n➢13/16 studies include only females\n➢No efficacy data in males\n➢Some evidence of lower antibody titers in adolescent males versus females after 1 dose\n▪Efficacy and immunogenicity in immunocompromised persons\n➢Limited data available; not planning to make changes to recommendation\n▪Efficacy and immunogenicity in older age groups\n➢Limited data available; need to decide appropriate upper age for our PICOs\n26Outstanding questions for reduced number of HPV vaccine doses\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention.\nThank you!", "summary": "Reduced number of doses for HPV vaccination series:  Work Group progress and literature update Carla L. DeSisto, PhD, MPH Co-Lead, HPV Vaccines Work GroupNational Center for Immunization and Respiratory Diseases Advisory Committee on Immunization Practices April 15, 2025 •PICO and outcomes •Introduction to systematic review •Updated data from studies of interest •Observational studies of HPV vaccine effectiveness •Outstanding questions for reduced  number of HPV vaccine dosesOutline 2 PICOs…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/02-DeSisto-HPV-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 27}
{"title": "03 Barnabas HPV 508", "content": "A randomized trial of single -dose HPV vaccination efficacy \namong young women: Month 54 durability results\nRuanne V. Barnabas, MBChB, DPhil\nChief, Division of Infectious Diseases, Massachusetts General Hospital\nDepartment of Medicine, Harvard Medical School\nHPV vaccination for all and catch -up vaccination to young adulthood \naccelerate the timeline to cervical cancer elimination.\nSimms, K. T., Steinberg, J., …, & Canfell , K. (2019). Impact of scaled up human papillomavirus vaccination: A modelling study. The Lancet OncologyPredicted number of cases of cervical cancer globally\nWe conducted a rigorous randomized trial (the KEN SHE Study) and found that the single \ndose HPV vaccination is highly efficacious, with 98% vaccine efficacy for HPV 16/18.\nPrimary Endpoint Period \nSix monthly follow -up visits: clinician collected cervical swabs \nEndpoint : Incident, persistent vaccine type -specific infection among participants HPV naïve \nat vaccination\nRetention  was 96% for four or more swab\nDuration of follow -up: 36 months\nBarnabas, R., Brown, E., and colleagues. KEN SHE Study 36 months VE results. Nature Medicine, Dec. 2023\nYoung women aged 15-20\nN=2,275 participants\nEnrolled\nn=757 participants\nImmediate \nmeningococcal vaccine\nControln=760 participants\nImmediate bivalent \nvaccine\n2vHPVn=758 participants\nImmediate nonavalent \nvaccine\n9vHPVRandomization\nParticipants were followed over 36 months.\nPhysician \ncollected \ncervical swabs \nfor HPV DNAFollow -up \n6 monthly\nVE \n18 monthsPrimary analysis\nExclude \nprevalent \ninfectionEnrollment and \nmonth 3\nPhysician collected \ncervical swabs for \nHPV DNA\nParticipants \nvaccinatedFollow -up \n6 monthly\nVE\n36 monthsFinal analysis\nParticipants with prevalent HPV infections at enrollment were excluded from \nthe per protocol/ mITT  analysis, because the vaccine is prophylactic only.\nmITT  HPV 16/18 cohort\n•29% (n=661/2,275) prevalent infections → excluded\nmITT  HPV 16/18/31/33/45/52/58 cohort\n•52% (n=792/1,515) prevalent infection → excluded\n9v VE= 99%  for HPV 16/18 (95% CI: 91 – 100%)\n2v VE= 98%  for HPV 16/18 (95% CI: 90 – 99%)\nVE=96%  for HPV 16/18/31/33/45/52/58 \n(95% CI: 89 – 98%)\nBarnabas, R., Brown, E., and colleagues. KEN SHE Study 36 months VE results. Nature Medicine, Dec. 2023Month 36 VE resultsAfter three years, single -dose HPV vaccine efficacy remained high and durable \n(VE= 98%  for HPV 16/18 and VE= 96%  for HPV 16/18/31/33/45/52/58).\nn=2\nn=1n=72\nn=84\nn=5\nWe hypothesized that single -dose vaccination would be effective and durable \nover 54 -months based on sustained antibody levels over 16 years.\n \nJoshi, S…Basu, P . Vaccine. 2023 Jan 4;41(1):236 -245. \nPorras, C … Kreimer , A. CVT, IPVC, 2023\nParticipants in the KEN SHE Study were crossed over at month 30/36 while \nmaintaining the study blind.\nEnrollment\nYoung women aged 15-20 years\nEligibility: 1-5 lifetime partners, HIV RDT \nnegative, No previous HPV vaccine or \ncontraindications, Resident\nImmediate \nmeningococcal vaccineImmediate bivalent HPV\nvaccineImmediate nonavalent \nHPVvaccineRandomized\nDelayed nonavalent HPV \nvaccineDelayed meningococcal \nvaccineDelayed meningococcal\nvaccineCrossover vaccination\nPrimary Endpoint Period \nCrossover Period \nAll Single -dose HPV \nVaccinated Period \nCrossover \nperiod  \n(vaccination at \nm 30 or m 36)All single -dose \nHPV vaccinated \nperiod\nDurability \nresultsFinal Endpoint \nperiod\nFinal RCT VE \nresults\nAIMS\n1. To evaluate effectiveness of single -dose HPV vaccination for age 18 -23, we compared the cumulative \nincidence of persistent HPV using Kaplan -Meier (cumulative incidence) curves and incident rate \nestimates for the immediate and delayed vaccine groups (graphic illustration)\n2. To assess durability, vaccine efficacy was evaluated as a function of time since vaccination using a Cox \nregression model  (accounting for time and time variable covariates)\n•Endpoint : Incident persistent vaccine type -specific HPV infection measured at two time points 6 \nmonths apart\n•Both analyses used the mITT  cohorts\nWe extended the KEN SHE Study in a blinded cross -over trial design to assess \nvaccine efficacy and durability at month 54.\n\nThere were no differences in baseline characteristics between study groups. \nParticipants were age 18 -23 years at cross -over vaccination. \nCharacteristics Nonavalent HPV\n(n=758)Bivalent HPV\n(n=760)Control\n(n=757)\nAge group 15 -17 years (%) 60% 56% 56%\nMedian age (years) 17 17 17\nSecondary school (%) 73% 73% 73%\nCurrent steady partner (%) 72% 71% 72%\nChlamydia trachomatis \npositive (%)12% 13% 14%\nPrevalence of baseline characteristics for the ITT cohort\nRetention was 90% for three or more swabs and the median time between endpoint \nswab collection was 6.00 months. \nRetention 90%  \nfor 3 post -crossover swabs\nMedian follow -up 53 months2,275 Participants \nenrolled\n22,124 ( 95% ) \nReceived crossover \nvaccine\nNo diff by study grpRetention 91% \nfor 5 or more pre -\ncrossover swabs\n151 (6.6%) \nexited\nThe incidence of persistent non -vaccine HPV types was stable across the time \nperiods and between the study groups, indicating continued HPV exposure. \n(26/35/39/40/42/43/44/51/53/54/56/59/61/66/68/69/70/73/82 in HPV 16/18 mITT  cohort)\nIncidence of persistent \nnon-vaccine type HPV \nper 100 woman -years \n(95% CI)Study Group\nDelayed HPV \nvaccinationImmediate HPV \nvaccinationOverall\nPrimary Endpoint \nPeriod19.5  \n(15.4 -24.3)20.7  \n(17.6 -24.2)20.3\n(17.8 -23.0)\nAll Single -dose HPV \nVaccinated Period22.0  \n(12.0 -36.9)22.5  \n(14.7 -33.0)22.3  \n(15.9 -30.3)\nFollow -up time amongst women non -vaccine HPV -type DNA negative at month 0 and month 3 (women are excluded if positive at month 0  or \nmonth 3 for any of HPV 26/35/39/40/42/43/44/51/53/54/56/59/61/66/68/69/70/73/82)\n                    \n                     \nDurability and Vaccine Efficacy (VE) Results\nCumulative Incidence of Persistent HPV 16/18 by Original Vaccine Group and Study \nPeriod (HPV 16/18 mITT Cohort)\nPre-crossover n = 4\nPost -crossover n = 4\n~14 months\nRandomized\nvaccineBlinded \ncrossover vaccineCumulative Incidence of Persistent HPV 16/18 by Original Vaccine Group and Study \nPeriod (HPV 16/18 mITT  Cohort)\nPre-crossover n = 4\nPost -crossover n = 4Pre-crossover n = 89\nPost -crossover n = 7\nParticipants vaccinated at age 18 -23 years, had similar low rates of incident \npersistent HPV 16/18 infection compared to vaccination at age 15 -20 years.\n\nVE to prevent HPV 16/18 \nas a function of time \nsince HPV Vaccination \n(HPV 16/18 mITT  Cohort)HPV 16/18 vaccine \nefficacy, VE=99.2% \n(95% CI 96.1 -99.9%) is \nsustained over time \nwithout evidence for \nwaning immunity. \n\nCumulative Incidence of Persistent HPV 16/18/31/33/45/52/58 by Original Vaccine \nGroup and Study Period (HPV 16/18/31/33/45/52/58 mITT  Cohort)\nPre-crossover n = 5\nPost -crossover n = 5\nCumulative Incidence of Persistent HPV 16/18/31/33/45/52/58 by Original Vaccine \nGroup and Study Period (HPV 16/18/31/33/45/52/58 mITT  Cohort)\n~14 monthsBlinded \ncrossover vaccine\nRandomized\nvaccine\nPre-crossover n = 5\nPost -crossover n = 5Pre-crossover n = 89\nPost -crossover n = 9\nParticipants vaccinated at age 18 -23 years, had similar rates of incident \npersistent HPV 16/18/31/33/45/52/58 infection compared to vaccination at \nage 15 -20 years.\n\nVaccine Efficacy to prevent HPV \n16/18/31/33/45/52/58 as a function of \ntime since HPV vaccination (HPV \n16/18/31/33/45/52/58 mITT  cohort)HPV \n16/18/31/33/45/52/\n58 vaccine efficacy, \nVE=98.9% (95% CI \n94.9 -99.8%) is \nsustained over time \nwithout evidence for \nwaning immunity. \n\nDiscussion\n•Adolescent girls and young women were effectively protected from \nHPV infection over the first 54 months post -vaccination\n•Rigorous design, high fidelity to the protocol, high retention, clear \nascertainment of outcomes → strong evidence for single -dose HPV \nvaccine efficacy for age up to 23 years\n•Single -dose VE 16/18 and 16/18/31/33/45/52/58 – lower bound of the \nCI is >94% - in keeping with licensure trials for three doses without \nevidence of waning\n•Adds to the growing body of evidence supporting the efficacy of single -\ndose HPV vaccine efficacy\n•Next step: Extension to evaluate clinical endpoints\nPatient perspectives\nShared Clinical Decision Making Increase Access to Prevention\n\nKEN SHE Study collaborators\nDr. Maricianah Onono Dr. Elizabeth BukusiDr. Betty Njoroge Dr. Nelly MugoKenya Medical Research Institute (KEMRI)\nFred Hutchinson Cancer Center\nUniversity of Washington\nDr. Denise GallowayDr. Elizabeth Brown\nDr. Rachel Winer\nGrace Umutesi\nChristine HathawayMassachusetts General \nHospital\nKate Heller\nJesse Heitner\nMeighan Krows\nOdun  Talabi\nThank you\nClinicalTrials.gov : \nNCT03675256•Study Participants\n•Bill and Melinda Gates Foundation (Peter Dull, Reena Gulati, Abdul Rawuf  Yousufzay , Sara Vernam );Division of Infectious Diseases, Department of Medicine, \nMassachusetts General Hospital (Ruanne  Barnabas, Kate Heller, Diane Kanjilal ,Meighan Krows , Odunayo  Talabi ),Fred Hutchinson Cancer Center (Elizabeth Brown, \nDenise Galloway, Jody Carter, Marci Wright, Priya R. Prabhu, Robin Smith, Deborah Donnell, Kidst  Zewdie); KEMRI Kisumu (Elizabeth A. Bukusi , Maricianah  Onono , \nSamya  S. Rashid, Annette A. Opondo, Catherine W. Mwakio ,  Christine A. Olweny , Cynthia Akinyi , David E. Muhoma , Debora A. Odhiambo, Donnavane  A. Ondego , \nFlorence A. Ondiek , George O. Omondi, Gilbert C. Mutai, Hellen A. Olweyo , Imelda N. Imali , Imeldah  N. Wakhungu , Janet A. Okeyo , Irene Okumu, Joan A. Ongere , Job A. \nOuma , Kevin O. Onyango, Linet A. Okode , Lizzie N. Kabete, Lyna  A. Memo, Maqline  A. Achola , Meldah  O. Adipo , Mildred A. Owenga , Millicent A. Oronje , Moses O. Siaji, \nNobert B. Walusala , Nollyne  A. Okuku , Penina N. Amboka , Rebecca A. Otieno, Reina Lenturkana , Robai  Mituyi , Simon M. Muthusi ,  Veronica O. Atogo , Dennis Kegode , \nDaisy Chepkoros , Ivy M. Mutuiri , Benard M. Muga, Caren A. Wemali , Enericah  K. Kanampiu , Geoffrey Kebaso , Mildred Imbayi , Teresia O. Akinyi , Rebecca A. Otieno, \nEsther A. Odeny , Elijah Mbuya, Stephen O. Abiero , Roseline Sikolia , David N. Marwa, Peter O. Mboya, Elizabeth L. Musi, Beryl A. Osoga , Vincent R. Ochuka , Vincent O. \nOdera, Lydiah  A. Okumu, Pius O. Atonga , Nollyne  A. Okuku , Vincent K. Salano , Adero  J. Cate, Nicholas Walukana , Timothy Kwena , Celestine Lihavi , Maureen A. Ochieng, \nRobai  M. Mituyi , Perez A. Odhiambo, Oyamo  O. Christopher, Katherin L. Amukonyi , Patricia Matti, Bill Nyongesa , Belder  A. Odedo , Jane A. Odaro , Mathias M. Wakwabi , \nCollins Ochola , Collins I. Mulonga , Nita C. Akech, Synthia Oguna , Grace A. Obinge , Fredrick Ochieng); KEMRI Nairobi (Betty Njoroge, Alice Njoki, Edna Nyandiga ,  Esther \nK. Charles, Esther Neema, Faith Ambiyo , John Okumu, Hellen W. Kimani, Paul Mutunga, Syovata  Kimanthi , Umi W. Mugo, Vincent Juma, Umi Mugo, Celina Muthii , Ian \nNg’ang’a , Vallery Obure , Vincent Omondi, Ephraim Njoroge, Florence Thuo );KEMRI Thika (Nelly Mugo, Agata Thumi , Anne Gaitho , Caren Koli, Catherine Kiptinness , \nCharlene Biwott, David Chege, Dorcas Kiboi , Edwin Mugo, Emily Anyango , Erick Koome , Faith Munyaka , Francis Khaemba , Fridah  Nkatha , Gladys Namboka , Grace \nNdung’u , Irene Kamau, Irene Njeru, Innes Wambui, Jacinta Nyokabi , Jane Gacheru ,  Jemimah Nyakio , John Njoroge, Josephine Njeri, Linda Orwa ,  Linet Makena, Lynda \nOluoch , Margaret Mwangi, Mary Kibatha , Mathew Irungu, Matilda Saina, Nina Ouko, Peter Mwenda, Peter Nzuve , Rispa  Nduuru , Rose Odera, Sammy Ng’ang’a , Sarah \nMbaire , Sarah Njoroge, Scholastica Wanjiku, Solomon Maina, Stanley Mwangi,  Stephen Gakuo , Veronica Muchoki , Victoria Wambui, Victor Munene,  Vincent Juma, \nVirginia Wangechi , Zachary Gathu , Jelioth  Muthoni, Sabina Ndichu , Faith Rolex); University of Washington, Mombasa (R. Scott McClelland, Emmanuel Kabare , Fatma H. \nMwidadi , Juma Shafi, Khamis Mwinyikai , Rukiya  Hassan, Salwa Mustafa); University of Washington, Seattle (Connie Celum , Elena A. Rechkina , Jared M. Baeten, Rachel \nJohnson, Rachel L. Winer, Stephen L. Cherne , Susan Morrison, Torin Schaafsma );DF/Net Research, Inc., Seattle (Angela Williams, Amra Hercinovic , Gavin Robertson, \nKrissa  Gunderson, Lisa Ondrejcek ,). The study is dedicated to Kowselia  Ramaswami ( Malitha ) Ramiah , Sarah Kanyi  Mugo, Reginalda  Auma  Onono , Edwina Muga, \nMary Nduta , and all our mothers.\n\n                    \n                     \nThank you", "summary": "A randomized trial of single -dose HPV vaccination efficacy  among young women: Month 54 durability results Ruanne V. Barnabas, MBChB, DPhil Chief, Division of Infectious Diseases, Massachusetts General Hospital Department of Medicine, Harvard Medical School HPV vaccination for all and catch -up vaccination to young adulthood  accelerate the timeline to cervical cancer elimination. Simms, K. T., Steinberg, J., …, & Canfell , K. (2019). Impact of scaled up human papillomavirus vaccination: A…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/03-Barnabas-HPV-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 27}
{"title": "04 Pingali HPV 508", "content": "2023 National Immunization Survey -Teen (NIS -Teen) \nData Summary \nCassandra (Sandy) Pingali, MPH, MS\nEpidemiologist \nSurveillance and Epidemiology Branch (SEB)\nImmunization Services Division (ISD)\nNCIRD\nACIP Meeting \nApril 15th, 2025National Center for Immunization and Respiratory Diseases \n\nNational Immunization Survey -Teen Methodology\n•Two phase survey\n-1stphase: random digit dialed cell phone survey of \nparents in households with teens age 13 -17 years\n-2ndphase: mailed survey of vaccination providers \n•Household survey collects socio -demographics, health \ninsurance status, and consent for provider survey.\n•Provider survey collects the types of vaccinations, number \nof doses, dates of administration, and other administrative \ndata about the health care facility.\n-Teens are classified as being up to date based on the \nACIP -recommended numbers of doses for each vaccine.\n•Sample size of 2023 NIS -Teen survey included data \ncollected from parents/guardians of 16,568 adolescents.\n-Born January 2005 -December 2010\n2\nCoverage with Routine Vaccines \nRecommended for Adolescents\n2023 National Immunization Survey -Teen \nEstimated vaccination coverage with selected vaccines and doses among adolescents aged 13 -17 years, by \nsurvey year —National Immunization Survey -Teen, United States, 2006 -2023\nCoverage with ≥1 Tdap and ≥1 MenACWY  has been high and stable since 2018. However, coverage \nwith ≥1 HPV vaccine and proportion HPV up to date is lower compared to other routine vaccines.  0102030405060708090100\n2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023Percent Vaccinated (%)\nSurvey Year≥1 Tdap\n≥1 MenACWY\n≥2 MenACWY\n≥1 HPV\n≥3 HPV\nHPV UTDSingle cellular  telephone \nsampling frame estimates\n4Pingali C, Yankey D, Chen M, et al. National Vaccination Coverage Among Adolescents Aged 13 –17 Years — National Immunization Sur vey-Teen, United States, 2023. MMWR Morb  Mortal Wkly  Rep 2024;73:708 –714.\nEstimated vaccination coverage with selected vaccines and doses among adolescents aged 13 -17 years, by survey year —\nNational Immunization Survey -Teen, United States, 2022 and 2023\nVACCINE2023\n(n=16,568)2022\n(n=16,043)SIGNIFICANT  \nIncrease or \nDecrease ?PERCENTAGE \nPOINT \nDIFFERENCE\nCOMPARED TO \n2022\n% (95% CI) % (95% CI)\n≥1 Tdap 89.0 (87.9 -90.0) 89.9 (88.9 -90.9) - -0.9\n≥1 MenACWY 88.4 (87.3 -89.4) 88.6 (87.6 -89.6) - -0.2\n≥2 MenACWY* 59.7 (56.2 -63.2) 60.8 (57.5 -63.9) - -1.1\nHPV Females and Males Combined\n≥1 HPV 76.8 (75.4 -78.1) 76.0 (74.7 -77.3) - 0.8\nHPV UTD 61.4 (59.9 -63.0) 62.6 (61.1 -64.0) - -1.1\nHPV Females Only \n≥1 HPV 78.5 (76.7 -80.2) 77.8 (75.8 -79.6) - 0.8\nHPV UTD 64.0 (61.9 -66.1) 64.6 (62.5 -66.6) - -0.6\nHPV Males Only \n≥1 HPV 75.1 (73.0 -77.1) 74.4 (72.5 -76.1) - 0.8\nHPV UTD 59.0 (56.7 -61.2) 60.6 (58.6 -62.6) - -1.6\n*Assessed among adolescents aged 17 years; MenACWY estimate does not include the 17 -year -old adolescents who received their firs t \nMenACWY dose at ≥16 years and do not need a second vaccine dose.\n5Pingali C, Yankey D, Chen M, et al. National Vaccination Coverage Among Adolescents Aged 13 –17 Years — National Immunization Sur vey-Teen, United States, 2023. MMWR Morb  Mortal Wkly  Rep 2024;73:708 –714.\nSimultaneous administration of HPV vaccine with other recommended vaccines among \nadolescents aged 13 –17 years who initiated HPV vaccine, by age at interview — National \nImmunization Survey –Teen (NIS -Teen), United States, 2023\nVaccinationsAdolescents who received ≥1 HPV vaccine\n(N = 12,995)Weighted % \n(95% C.I.)\nReceived 1+ HPV vaccine 12,995 - \nReceived HPV vaccine only in a single visit 3,874 30.5 (29.0 -32.1)\nReceived HPV vaccine and one or more vaccine (s) in a \nsingle visit (Tdap, MenACWY , and/or flu vaccine)9,121 69.5 (67.9 -71.0)\nReceived Tdap and MenACWY and HPV vaccines in a \nsingle visit6,579 47.8 (46.0 -49.5)\n6\nCoverage with Routine Vaccines \nRecommended for Adolescents by \nSociodemographic Factors and Access to \nHealthcare \n2023 National Immunization Survey -Teen\nEstimated vaccination coverage with selected vaccines among adolescents aged 13 -17 years, by metropolitan statistical area \n(MSA status) – National Immunization Survey -Teen (NIS -Teen), United States, 2023\n89.2 89.180.1\n64.489.1 88.6\n74.8\n60.887.6 85.2\n72.5\n53.1\n0102030405060708090100\n≥1 Tdap ≥1 MenACWY ≥ 1 HPV HPV UTDPercent Vaccinated\nMSA Principal City (Mostly Urban) MSA Non-Principal City (Mostly Suburban) Non-MSA (Mostly Rural)**\n*\n*\nCoverage with ≥1 HPV vaccine and proportion HPV UTD is lower  in mostly suburban and mostly rural areas \ncompared to mostly urban areas. * Statistically significant difference (p<0.05); referent group was MSA principal city\n8\nEstimated vaccination coverage with selected vaccines among adolescents aged 13 -17 years, by health insurance status – \nNational Immunization Survey -Teen (NIS -Teen), United States, 2023\n90.1 89.4\n76.5\n63.288.6 88.479.1\n62.888.4 85.375.4\n56.679.8 80.6\n59.9\n31.4\n0102030405060708090100\n≥1 Tdap ≥1 MenACWY ≥ 1 HPV HPV UTDPercent Vaccinated\nPrivate Insurance Any-Medicaid Other Insurance Uninsured* *\n*\n**\n* Statistically significant difference (p<0.05); referent group was private insurance\n•Overall, vaccination coverage was lower  among uninsured adolescents than privately insured \nadolescents for all vaccines. \n•Those with “other” insurance had a lower  percentage HPV UTD than privately insured adolescents. \n•Adolescents with private and any Medicaid insurance had similar vaccination coverage, including \ncoverage with the HPV vaccine.  9\nEstimated vaccination coverage with ≥1 human papillomavirus (HPV) vaccine among adolescents 13 -17 years, by Health \nInsurance Status — National Immunization Survey –Teen (NIS -Teen), United States, 2015 -2023.\n020406080100\n2015 2016 2017 2018 2019 2020 2021 2022 2023Percent Vaccinated\nSurvey Year\nPrivate Only Any-Medicaid\nHistorically, adolescents insured by Medicaid had higher  coverage with ≥1 HPV vaccine compared to privately \ninsured adolescents. However, in 2022 and 2023, adolescents with private and any Medicaid insurance had similar \n≥ 1 HPV vaccine coverage.  \n10\nEstimated vaccination coverage with selected vaccines among adolescents aged 13 -17 years, by race and ethnicity – National \nImmunization Survey -Teen (NIS -Teen), United States, 2023\n88.9 87.4\n74.0\n60.688.1 89.077.3\n59.089.5 89.481.0\n63.688.6 85.777.167.590.0 92.4\n79.5\n64.689.1 88.277.2\n60.9\n020406080100\n≥1 Tdap ≥1 MenACWY ≥ 1 HPV HPV UTDPercent Vaccinated\nWhite, NH Black, NH Hispanic AIAN, NH Asian, NH Multiracial, NH*\n*\n* Statistically significant difference (p<0.05); referent group was White, NH adolescents \n•Although historically, Black and Hispanic adolescents have had higher  coverage with ≥1 HPV vaccine than \nWhite adolescents, in 2023, only Hispanic adolescents had higher coverage. \n•In 2023, coverage with ≥1 MenACWY was higher  among Asian  adolescents compared to White adolescents.   \n11\nEstimated vaccination coverage with ≥1 dose of HPV vaccine among adolescents aged 13 –17 years, National \nImmunization Survey –Teen (NIS -Teen), United States, 2023\nAK\nHI\nDC 60%-74%\n77%-78%\n79%-83%\n84%-93%\nU.S coverage with ≥1 dose HPV vaccine was 77%.\n Mississippi had the lowest  coverage (60%), and Rhode Island had the highest  coverage with ≥1 HPV vaccine (93%). \n12\nInitiation of HPV Vaccine by Age\nAge at Initiation of HPV Vaccine — National Immunization Survey –Teen (NIS -Teen), United States, 2018 and \n2023.\n3.842.5\n21.732\n5.757.1\n1423.3\n0102030405060708090100\n9-10 years 11-12 years 13-17 years Never VaccinatedPercent Initiating HPV Vaccination\n2018 2023\n•HPV vaccine initiation at ages 9 -10 years and 11 -12 years has increased from 2018 to 2023. \n•HPV vaccine initiation at age 13 -17 years has decreased from 2018 to 2023. \n14\nOverall Summary\n•In 2023, 76.8% of adolescents aged 13 -17 years had initiated the HPV vaccine and 61.4% were HPV UTD.\n•This is the second  consecutive year that HPV vaccination coverage did not increase among adolescents aged \n13-17 years.\n•HPV vaccination coverage remains lower than coverage for Tdap and MenACWY vaccines. \n \n•In 2023, 5.7% of adolescents initiated the HPV vaccine at ages 9 -10 years and 57.1% of adolescents initiated \nthe HPV vaccine at ages 11 -12 years. \n  \n•The HPV vaccine is commonly given with other vaccines with 48% receiving the HPV vaccine, and Tdap \nvaccine, and MenACWY vaccine in a single visit. Only 31% of adolescents received an HPV vaccine without \nany other vaccine. \n \n•HPV vaccination coverage varies by sociodemographic factors, access to healthcare, and by state. 2023 NIS -Teen HPV Coverage Data Summary \n16\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official \nposition of the Centers for Disease Control and Prevention.\nThank you!\n• David Yankey\n• Michael Chen\n• Madeleine Valier \n• Laurie Elam -Evans\n• Jim Singleton \n• Shannon Stokley \n• Lauri Markowitz\n• Carla DeSisto\n• Sarah Schillie\n• Michelle Hughes", "summary": "2023 National Immunization Survey -Teen (NIS -Teen)  Data Summary  Cassandra (Sandy) Pingali, MPH, MS Epidemiologist  Surveillance and Epidemiology Branch (SEB) Immunization Services Division (ISD) NCIRD ACIP Meeting  April 15th, 2025National Center for Immunization and Respiratory Diseases   National Immunization Survey -Teen Methodology •Two phase survey -1stphase: random digit dialed cell phone survey of  parents in households with teens age 13 -17 years -2ndphase: mailed survey of…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/04-Pingali-HPV-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 17}
{"title": "05 Kim HPV 508", "content": "Population -Based Health Impact of \nSingle -Dose HPV Vaccination \nin the United States\nJane J. Kim, Ph.D.\nAdvisory Committee on Immunization Practices\nApril 15, 2025\n\nModeling Teams\nHarvard University\n•Jane Kim\n•Emily Burger\n•Nicole Campos\n•Mary Caroline Regan\n•Jennifer Spencer\n•Stephen Sy\nUniversit é Laval\n•Marc Brisson\n•Jean -Francois Laprise\n•Mélanie  Drolet\n•Éléonore Chamberland\n•Chantal Sauvageau\n•Élodie BénardFunding\n•PATH Single -Dose HPV Consortium\n•NIH/NCI CISNET Consortium (Grant \nNumber U01 CA253912 )\n•Université Laval\n•CIHR\n•NACI/CCNI\n•Digital Research Alliance of Canada\nThe authors declare no conflicts of interest.Acknowledgments\nWe would like to acknowledge Lauri \nMarkowitz, Harrell Chesson, and Mark Jit \nfor their contributions to related work.\nObjectives\nUsing two independently -developed mathematical models adapted \nto the U.S. population:\n•To project the long -term health effects of single -dose  HPV vaccination , \ntaking into account historical HPV vaccination coverage in the U.S. \npopulation.\n•To explore key uncertainties of single -dose  HPV vaccine efficacy and \nduration on the population -level effectiveness.\nHarvard1-2 HPV -ADVISE3-5\nModel Type Individual -based sexual transmission model (includes herd immunity)\nPopulation Population -based (multi -cohort); females and males by single -year age\nMixing, Risk Groups Heterosexual mixing among 4, age -stratified risk groupsModel Overview\n1. Kim, PLOS Med 2021; 2. Burger, JNCI Mono 2024; 3. Brisson, JNCI 2016; 4. Laprise, J Infect Dis 2016; 5. Laprise, Ann Inter n Med 2020.\nHarvard1-2 HPV -ADVISE3-5\nModel Type Individual -based sexual transmission model (includes herd immunity)\nPopulation Population -based (multi -cohort); females and males by single -year age\nMixing, Risk Groups Heterosexual mixing among 4, age -stratified risk groups\nHPV GenotypesHPV -16, -18, -31, -33, -45, -52, -58 \n(modeled separately) + pooled high -risk \n+ pooled low -riskHPV -16, -18, -31, -33, -45, -52, -58, -6,      \n-11, -35, -39, -51, -56, -59, -66, -68, -73, \nand -82 (modeled separately)\nHPV TransmissionProbability per month of partnership \nduration  (sex and genotype -specific)Probability per sexual act (sex and \ngenotype -specific)\nHealth StatesNo HPV, HPV, CIN2, CIN3, cervical cancer \n(SCC, by stage), deathNo HPV, HPV, CIN1 , CIN2, CIN3, cervical \ncancer (SCC, by stage), deathModel Overview\n1. Kim, PLOS Med 2021; 2. Burger, JNCI Mono 2024; 3. Brisson, JNCI 2016; 4. Laprise, J Infect Dis 2016; 5. Laprise, Ann Inter n Med 2020.\nModel Fit to HPV Prevalence:  Harvard\nPre-Vaccine\n(2002 -2008)\nPost -Vaccine\n(2013 -2016)\n* Centers for Disease Control and Prevention. National Health and Nutrition Examination Survey (NHANES). http://www.cdc.gov/n chs/nhanes.htm.\n\nModel Fit to HPV Prevalence: HPV -ADVISE (US)\nPre-Vaccine\n Post -Vaccine\n(2005 -2006) (2013 -2014)\n* Centers for Disease Control and Prevention. National Health and Nutrition Examination Survey (NHANES). http://www.cdc.gov/n chs/nhanes.htm.\nModel Fit to Median Lifetime Partners\nHarvard HPV -ADVISE\n2006\n2025+2011\n2015Change Protection Ages + Doses Population\nVaccine\nIntroduced; \ngirls only\n3d\n9 26 4v GIRLS\n9 219 26\n4v\n 3dBoys\naddedGIRLS\nBOYS\n15 9 26 45\n15 9 45 269v\n 3d\n 2dShared\ndecision making\nfor ages 27 -45)GIRLS\nBOYS\n9 45\n9 459v 1dConsidering\none dose*GIRLS\nBOYS20199 219 26\n9v9v vaccine; \nTwo doses if < 15GIRLS\nBOYS\n3d\n 2d\n1515U.S. Vaccination Policy\n*1 dose through age 45 years scenario is for illustrative purposes only, to show the maximum possible difference between 1 -dose strategies vs. the current strategy.\nVaccine Assumptions & Justifications\n▪Empirical data: VE against persistent HPV16/18 infection = 92 -99%1-4\n– Base -case scenario : VE = 98% (Non -inferior VE, based on the KEN SHE trial3)\n– Worst -case scenario:  VE = 90% (Lower bound 95% CI of the KEN SHE trial3)1-dose vaccine efficacy (VE)\n1. Basu, Lancet Oncol 2021; 2. Malvi , JNCI Mono 2024; 3. Barnabas , Nature Med 2023; 4. Barnabas , IPVC 2024; 5. Porras, JNCI Mono 2024 ▪Empirical data: Sustained protection 12-16 years (IARC India Study & CVT)1,2,5\n– Base -case scenario: VD = Lifelong\n– Worst -case scenario: VD = average 25 years\n•Normal distribution (Std Dev = 5 years ) reflects stable efficacy followed by steep drop in protection \n•Implies waning starts 15 years after vaccination for some individuals\n•Implies no protection for 50% of individuals 25 years  after vaccination \n•Implies no protection for all individuals 35 -40 years after vaccination \n•VD=10 years: excluded from the analysis as waning would have been observed 1-dose vaccine duration (VD) \nBrisson, JNCI Mono 2024; IARC ( Malvi , JNCI Mono 2024); KEN SHE (Barnabas, Nature Med 2023 & Barnabas, IPVC 2024); CVT (Porras, JNCI Mono 2024)Worst -case: VE = 90%Vaccine Efficacy Assumptions vs Data for Single -Dose\nVaccine efficacy against persistent HPV -16/18 infection, Vaccine duration (VD) = life\nBase case: VE = 98%\n\nVaccine Duration Assumptions vs Data for Single -Dose\nVaccine efficacy against persistent HPV -16/18 infection, Vaccine efficacy (VE) = 98%\nWorst -case: VD = 25and 35years Base case: VD = Lifelong\nBrisson, JNCI Mono 2024; IARC ( Malvi , JNCI Mono 2024); KEN SHE (Barnabas, Nature Med 2023 & Barnabas, IPVC 2024); CVT (Porras, JNCI Mono 2024)\nRESULTS\nWhat is the impact of switching to 1 -dose \nvaccination in the United States?\nYear YearHPV -16 Relative Incidence in Females\nCervical Cancer Relative IncidenceResults:  Switching to 1 -Dose -Non -inferior 1 -Dose\nGender -neutral 9 -valent vacc , 2-Dose VE=98%, 2 -Dose VD=Life, U.S. coverage\nHPV -16 Cervical Cancers\nSwitch to \n1-doseSwitch to \n1-dose\nRelative incidence calculated against no vaccination.Harvard \nHarvard \nLaval \nYear YearHPV -16 Relative Incidence in Females\nCervical Cancer Relative IncidenceHPV -16\nSwitch to \n1-doseResults:  Switching to 1 -Dose -Non -inferior 1 -Dose\nGender -neutral 9 -valent vacc , 2-Dose VE=98%, 2 -Dose VD=Life, U.S. coverage\nCervical Cancers\nSwitch to \n1-dose\nRelative incidence calculated against no vaccination.\nHarvard \nLaval \nYear YearHPV -16 Relative Incidence in Females\nCervical Cancer Relative IncidenceHPV -16\nSwitch to \n1-doseResults:  Switching to 1 -Dose -Non -inferior 1 -Dose\nGender -neutral 9 -valent vacc , 2-Dose VE=98%, 2 -Dose VD=Life, U.S. coverage\nCervical Cancers\nWith 2-dose or non -inferior 1 -dose \n9-valent HPV vaccination , the \nmodel projects near elimination of \nHPV-16 infections and >90% \nreduction in cervical cancers.Switch to \n1-dose\nRelative incidence calculated against no vaccination.\nModel Means \nYear YearHPV -16 Relative Incidence in Females\nCervical Cancer Relative IncidenceHPV -16\nSwitch to \n1-doseResults:  Switching to 1 -Dose -Non -inferior 1 -Dose\nGender -neutral 9 -valent vacc , 2-Dose VE=98%, 2 -Dose VD=Life, U.S. coverage\nCervical Cancers\nSwitch to \n1-dose\nRelative incidence calculated against no vaccination; lines represent the mean model projections from the Harvard and HPV -ADVISE  US models.\nYear YearHPV -16 Relative Incidence in Females\nCervical Cancer Relative IncidenceResults:  Switching to 1 -Dose -Lower 1 -Dose VE (90%)\nGender -neutral 9 -valent vacc , 2-Dose VE=98%, 2 -Dose VD=Life, U.S. coverage\nSwitch to \n1-dose\nVE=90%HPV -16 Cervical Cancers\nUnder the worst -case assumption \nof vaccine efficacy (90%) , 1-dose \nvaccination is projected to produce \nsimilar population -level impacts as \n2-dose or non -inferior 1 -dose.Switch to \n1-dose\nRelative incidence calculated against no vaccination; lines represent the mean model projections from the Harvard and HPV -ADVISE  US models.Non -inferior\nResults:  Switching to 1 -Dose -Waning 1 -Dose VD (25 years)\nGender -neutral 9 -valent vacc , 2-Dose VE=98%, 2 -Dose VD=Life, U.S. coverage\nHPV -16\nSwitch to \n1-dose\nVD=25 yearsCervical Cancers\nRelative incidence calculated against no vaccination; lines represent the mean model projections from the Harvard and HPV -ADVISE  US models.Year YearHPV -16 Relative Incidence in Females\nCervical Cancer Relative IncidenceNon -inferior\nEven with waning 1 -dose \nprotection (average of 25 years) , \n1-dose vaccination is projected to \nproduce similar population -level \nimpacts as 2 -dose or non -inferior \n1-dose.Switch to \n1-dose\nResults:  Switching to 1 -Dose - Lower VE (90%) & Wane (25y)\nGender -neutral 9 -valent vacc , 2-Dose VE=98%, 2 -Dose VD=Life, U.S. coverage\nYear YearHPV -16 Relative Incidence in Females\nCervical Cancer Relative IncidenceHPV -16\nSwitch to \n1-doseCervical Cancers\nVE=90% and\n   VD=25 yearsNon -inferior\nAssuming both lower VE (90%) and \nwaning 1 -dose protection (average \n25y) , 1-dose vaccination is \nprojected to produce slight rise in \nHPV incidence (~2045) and cervical \ncancer incidence (~2060).Switch to \n1-dose\nResults:  Switching to 1 -Dose – Summary\nGender -neutral 9 -valent vacc , 2-Dose VE=98%, 2 -Dose VD=Life, U.S. coverage\nYear YearHPV -16 Relative Incidence in Females\nCervical Cancer Relative IncidenceHPV -16\nSwitch to \n1-doseCervical Cancers\nNon -inferior\nAll scenarios result in similar \nreductions in HPV -16 and cervical \ncancer incidence over time.Switch to \n1-dose\nVD=25 yearsVE=90%\nVE=90% and\n   VD=25 years\nHow do these findings compare against \npreviously published results?\nResults  Impact of switching to 1 dose –1-dose VD=25 years\nGender -neutral 9 -valent vaccination, 2 -dose VE=98%,  2 -dose VD=Life, VC=85%\nHPV-16 new infections among Females\n Cervical cancers (SCC)\nBrisson JNCI, 2024; the lines are the median result of model projections using 100 parameter sets (50 from HPV -ADVISE US and 50 from HPV -ADVISE Canada); Relative incidence \ncalculated as % incidence vs no vaccination; HPV infection results excludes reactivation or deposition of HPV infections.\n▪What is the impact of 1-dose vaccine efficacy for males?  \n–In a pessimistic scenario of lower 1 -dose vaccine  efficacy (70%) for males only, HPV-ADVISE  showed a \nsimilar population -level impact as non -inferior 1-dose for all individuals.\n–Herd effects would mitigate a lower vaccine efficacy for males i f gender -neutral vaccination coverage is \nhigh and vaccine efficacy for females is high and long lasting .\n▪What is the impact of 1 -dose vaccination on non -cervical HPV -related cancers ?\n–More work is required to better understand the natural history of these cancers and the potential \nimpact of 1 -dose vaccination on their epidemiology.\n–Prior analyses suggest more limited/delayed rebound for other HPV -related cancers for all pessimistic \n1-dose scenarios given slower progression from infection to cancer.1\n▪Can mitigation strategies offset  potential rebounds in infection and cancer?\n–Both models have shown  that if ongoing trial data were to signal waning (i.e., in the next 10 years), \nswitching back to a 2 -dose regimen would mitigate any rebounds in HPV -16 and cervical cancer.1-3\n–Mitigation strategies could be population -level and would not require revaccinating those who received \n1 dose to be successful.Other Scenarios Explored in Prior Analyses\n1. Drolet, CMAJ 2024; 2. Bénard, Lancet Public Health 2023; 3. Burger, JNCI Mono 2024 \nConclusions: 1-Dose HPV Vaccination in the U.S.\n▪Switching to 1 -dose HPV vaccination is projected to have similar reductions in \nHPV and cervical cancer incidence as continuing with 2 doses in the U.S.\n▪Under the pessimistic assumptions of vaccin e efficacy (90%) and vaccine \nduration (25 years), a switch to 1 -dose vaccination is projected to have limited \nrebound in HPV infection and cervical cancer incidence.\n–Switching to 1 -dose vaccination would occur when HPV prevalence is low due to high 2 -dose \nvaccination coverage in the U.S.\n–Individuals  would be protected during their peak ages of sexual activity, providing direct protection \nand herd effects to unprotected adults.\n▪Continued monitoring of 1 -dose protection over time is required to rapidly \ndetect any potential signs of waning protection and introduce mitigation \nstrategies, if needed.\n–Under pessimistic assumptions of 1 -dose duration of protection, switching back to 2 -dose vaccination \nis projected to mitigate losses in cervical cancer prevention.\nReferences\n•Basu P , Malvi SG, Joshi S, Bhatla  N, Muwonge R, Lucas E, et al. Vaccine efficacy against persistent human papillomavirus (HPV) 16/18 infection at 10 years afte r \none, two, and three doses of quadrivalent HPV vaccine in girls in India: a multicentre , prospective, cohort study. Lancet Oncol. 2021 Nov;22(11):1518 -1529. doi: \n10.1016/S1470 -2045(21)00453 -8. Epub  2021 Oct 8. Erratum in: Lancet Oncol. 2022 Jan;23(1):e16. doi: 10.1016/S1470 -2045(21)00700 -2. PMID: 34634254; \nPMCID: PMC8560643.\n•Barnabas RV, Brown ER, Onono  MA, Bukusi  EA, Njoroge B, Winer RL, et al. Durability of single -dose  HPV vaccination in young Kenyan women: randomized \ncontrolled trial 3 -year results. Nat Med. 2023 Dec;29(12):3224 -3232. doi: 10.1038/s41591 -023-02658 -0. Epub  2023 Dec 4. PMID: 38049621; PMCID: \nPMC10719107. \n•Brisson M, Laprise JF, Chesson HW, Drolet M, Malagon T, Boily MC, et al. Health and Economic Impact of Switching from a 4 -Valent  to a 9 -Valent HPV Vaccination \nProgram in the United States. J Natl Cancer Inst. 2016;108(1).\n•Burger EA, Laprise JF, Portnoy A, Spencer JC, Sy S, Regan MC, Bénard É, Drolet M, Brisson M, Kim JJ. Population -level health imp act of hypothetical waning 1 -dose \nhuman papillomavirus vaccination and 2 -dose mitigation strategies in a high cervical cancer burden setting. J Natl Cancer Inst Monogr . 2024 Nov 1;2024(67):379 -\n386. doi: 10.1093/ jncimonographs /lgae039. PMID: 39529530; PMCID: PMC11555273. \n•Kim JJ, Simms KT, Killen J, Smith MA, Burger EA, Sy S, Regan C, Canfell K. Human papillomavirus vaccination for adults aged 3 0 to 45 years in the United States: A \ncost-effectiveness analysis. PLoS  Med. 2021 Mar 11;18(3):e1003534. doi: 10.1371/journal.pmed.1003534. PMID: 33705382; PMCID: PMC7951902.\n•Laprise JF, Markowitz LE, Chesson HW, Drolet M, Brisson M. Comparison of 2 -Dose and 3 -Dose 9 -Valent Human Papillomavirus Vaccine  Schedules in the United \nStates: A Cost -effectiveness Analysis. J Infect Dis. 2016;214(5):685 -8.\n•Laprise JF, Chesson HW, Markowitz LE, Drolet M, Martin D, Benard E, et al. Effectiveness and Cost -Effectiveness of Human Papillo mavirus Vaccination Through Age \n45 Years in the United States. Ann Intern Med. 2020;172(1):22 -9.\n•Malvi SG, Esmy PO, Muwonge R, Joshi S, Poli URR, Lucas E, et al. A prospective cohort study comparing efficacy of 1 dose of q uadrivalent human papillomavirus \nvaccine to 2 and 3 doses at an average follow up of 12 years postvaccination. J Natl Cancer Inst Monogr . 2024 Nov 1;2024(67):317 -328. doi: \n10.1093/ jncimonographs /lgae042. PMID: 39529521; PMCID: PMC11555276. \n•Porras C, Romero B, Kemp T, Fantin R, Herrero R, Hildesheim A, et al. HPV16/18 antibodies 16 -years after single dose of bivalent  HPV vaccination: Costa Rica HPV \nvaccine trial. J Natl Cancer Inst Monogr . 2024 Nov 1;2024(67):329 -336. doi: 10.1093/ jncimonographs /lgae032. PMID: 39529529; PMCID: PMC11555268.", "summary": "Population -Based Health Impact of  Single -Dose HPV Vaccination  in the United States Jane J. Kim, Ph.D. Advisory Committee on Immunization Practices April 15, 2025  Modeling Teams Harvard University •Jane Kim •Emily Burger •Nicole Campos •Mary Caroline Regan •Jennifer Spencer •Stephen Sy Universit é Laval •Marc Brisson •Jean -Francois Laprise •Mélanie  Drolet •Éléonore Chamberland •Chantal Sauvageau •Élodie BénardFunding •PATH Single -Dose HPV Consortium •NIH/NCI CISNET Consortium (Grant …", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/05-Kim-HPV-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 26}
{"title": "06 Stefanos HPV 508", "content": "Evidence to Recommendations Framework\nWording of the age for routine HPV vaccination\nRuth Stefanos, MD, MPH\nAdvisory Committee on Immunization Practices\nApril 15, 2025National Center for Immunization and Respiratory Diseases\n1\nCurrent recommendation\nhttps://www.cdc.gov/acip -recs/hcp/vaccine -specific/hpv.html•HPV vaccination is routinely recommended at age 11 or 12 years\n•Vaccination can be given starting at age 9 years\n•Since 2006 (first ACIP recommendation), the wording of age at HPV \nvaccination initiation has not substantially changed\n2\n1996 The adolescent platform at 11 -12 years was established as “a new strategy \nto improve the delivery of vaccination services to adolescents and to \nintegrate recommendations for vaccination with other preventive services \nprovided to adolescents.” \nImmunization of adolescents. MMWR Recomm  Rep. 1996;45(RR -13):1 -16.\n2006Adolescent platform\n3Society for Adolescent Health and Medicine endorsed “three distinct \nadolescent vaccination visits/platforms for adolescents (11 –12-year visit, 14 –\n15-year visit, and a 17 –18-year visit) to integrate and emphasize the role of \nvaccination in already recommended comprehensive health care screening \nand provision visits.”\nMiddleman AB, Rosenthal SL, Rickert VI, et al. J Adolesc  Health. 2006;38(3):321 -327.\nYear of Recommendation Vaccine Recommended Age\n1995 Td 11–12 yrs\n2005 Tdap, 11–12 yrs\nMenACWY\n2006 HPV 11–12 yrs\n2010 MenACWY  booster 16 yrs\n2015 MenB * 16–18 yrs preferredAdolescent vaccination recommendations\n4 *shared clinical decision -making and individuals who are at increased risk\n5Representation of HPV vaccination recommendations \non child and adolescent i mmunization schedule, 2007\nhttps://www.cdc.gov/mmwr/PDF/wk/mm5551 -Immunization.pdf\n\n6Vaccine Birth 1 \nmo2 \nmos4 \nmos6 \nmos9 \nmos12 \nmos15 \nmos18 \nmos19–\n23 \nmos2–3 \nyrs4–6 \nyrs7–10 yrs 11–\n12 \nyrs13–\n15 \nyrs16 \nyrs17–\n18 \nyrs\nHPV\nRange of \nrecommended \nages for all \nchildrenRange of \nrecommended \nages for catch-\nup \nimmunizationRange of \nrecommended \nages for \ncertain high-\nrisk groupsRange of \nrecommended \nages for non-high-\nrisk groups that \nmay receive \nvaccine, subject \nto individual \nclinical decision \nmaking ttps://www.cdc.gov/vaccines/hcp/imz-schedules/downloads/past/2017-child.pdfSee \nfootnote \n13\nhRepresentation of HPV vaccination recommendations \non child and adolescent i mmunization schedule, 2017\n7 Notes and full schedule available at: https://www.cdc.gov/vaccines/hcp/imz -schedules/child -adolescent -age.htmlVaccine Birth 1 \nmo2 \nmos4 \nmos6 \nmos9 \nmos12 \nmos15 \nmos18 \nmos19–\n23 \nmos2–3 \nyrs4–6 \nyrs7–10 yrs 11–\n12 \nyrs13–\n15 \nyrs16 \nyrs17–\n18 \nyrs\nHPVSee \nnotes\nRange of \nrecommended \nages for all \nchildrenRange of \nrecommended \nages for catch-\nup vaccinationRange of \nrecommended \nages for \ncertain high-\nrisk groupsRecommended \nvaccination can \nbegin in this age \ngroupRepresentation of HPV vaccination recommendations on Table 1 \nof the child and adolescent i mmunization schedule, 2022 –2025\nPolicy question\nShould the ACIP recommendations state:\nHPV vaccination is routinely recommended at age 9 –12 years\n  instead of\nHPV vaccination is routinely recommended at age 11 or 12 years; \nvaccination can be given starting at age 9 years\n8\nEvidence to Recommendations ( EtR) Framework\nEtR Domain Question\nPublic Health ProblemIs the problem of public health importance?\nBenefits and HarmsHow substantial are the desirable anticipated effects?\nHow substantial are the undesirable anticipated effects?\nDo the desirable effects outweigh the undesirable effects?\nWhat is the overall certainty of this evidence for the critical outcomes? \nValuesDoes the target population feel that the desirable effects are large relative to \nundesirable effects?\nIs there important uncertainty about or variability in how much people value the \nmain outcomes?\nAcceptabilityIs the intervention acceptable to key stakeholders?\nResource UseIs the intervention a reasonable and efficient allocation of resources?\nEquityWhat would be the impact on health equity?\nFeasibilityIs the intervention feasible to implement?\n9\nEvidence to Recommendations ( EtR) Framework\nEtR Domain Question\nPublic Health ProblemIs the problem of public health importance?\nBenefits and HarmsHow substantial are the desirable anticipated effects?\nHow substantial are the undesirable anticipated effects?\nDo the desirable effects outweigh the undesirable effects?\nWhat is the overall certainty of this evidence for the critical outcomes? \nValuesDoes the target population feel that the desirable effects are large relative to \nundesirable effects?\nIs there important uncertainty about or variability in how much people value the \nmain outcomes?\nAcceptabilityIs the intervention acceptable to key stakeholders?\nResource UseIs the intervention a reasonable and efficient allocation of resources?\nEquityWhat would be the impact on health equity?\nFeasibilityIs the intervention feasible to implement?\n10\nEvidence to Recommendations ( EtR) Framework\nEtR Domain Question\nPublic Health ProblemIs the problem of public health importance?\nBenefits and HarmsHow substantial are the desirable anticipated effects?\nHow substantial are the undesirable anticipated effects?\nDo the desirable effects outweigh the undesirable effects?\nWhat is the overall certainty of this evidence for the critical outcomes? \nAcceptability/ValuesIs the intervention acceptable to key stakeholders?\nDoes the target population feel that the desirable effects are large relative to \nundesirable effects?\nIs there important uncertainty about or variability in how much people value the \nmain outcomes?\nResource UseIs the intervention a reasonable and efficient allocation of resources?\nEquityWhat would be the impact on health equity?\nFeasibilityIs the intervention feasible to implement?\n11\nEvidence to Recommendations ( EtR) Framework\nEtR Domain Question\nPublic Health ProblemIs the problem of public health importance?\nBenefits and HarmsHow substantial are the desirable anticipated effects?\nHow substantial are the undesirable anticipated effects?\nDo the desirable effects outweigh the undesirable effects?\nWhat is the overall certainty of this evidence for the critical outcomes? \nAcceptability/ValuesIs the intervention acceptable to key stakeholders?\nDoes the target population feel that the desirable effects are large relative to \nundesirable effects?\nIs there important uncertainty about or variability in how much people value the \nmain outcomes?\nResource UseIs the intervention a reasonable and efficient allocation of resources?\nEquityWhat would be the impact on health equity?\nFeasibilityIs the intervention feasible to implement?\n12\nEvidence to Recommendations ( EtR) Framework\nEtR Domain Question\nPublic Health ProblemIs the problem of public health importance?\nBenefits and HarmsHow substantial are the desirable anticipated effects?\nHow substantial are the undesirable anticipated effects?\nDo the desirable effects outweigh the undesirable effects?\nAcceptability/ValuesIs the intervention acceptable to key stakeholders?\nDoes the target population feel that the desirable effects are large relative to \nundesirable effects?\nIs there important uncertainty about or variability in how much people value the \nmain outcomes?\nResource UseImpact on cost -effectiveness will likely be minimal.\nEquityWhat would be the impact on health equity?\nFeasibilityIs the intervention feasible to implement?\n13\nEvidence to Recommendations ( EtR) Framework\nEtR Domain Question\nPublic Health ProblemIs the problem of public health importance?\nBenefits and HarmsHow substantial are the desirable anticipated effects?\nHow substantial are the undesirable anticipated effects?\nDo the desirable effects outweigh the undesirable effects?\nAcceptability/ValuesIs the intervention acceptable to key stakeholders?\nDoes the target population feel that the desirable effects are large relative to \nundesirable effects?\nIs there important uncertainty about or variability in how much people value the \nmain outcomes?\nResource UseImpact on cost -effectiveness will likely be minimal.\nEquityWhat would be the impact on health equity?\nFeasibilityIs the intervention feasible to implement?\n14\nPublic Health Problem\nIs HPV -related disease of public health importance?\n15\nEstimated HPV -associated and HPV -attributable cancer \ncases per year, United States, 2017 –2021\nCancer siteNumber  of HPV -\nassociated \ncancersPercentage \nprobably caused \nby any HPV typeEstimated number probably caused by \nany HPV type*\nFemale Male Both sexes\nCervix 11,959 91% 10,800 0 10,800\nVagina 898 75% 700 0 700\nVulva 4,418 69% 3,000 0 3,000\nPenis 1,381 63% 0 900 900\nAnus** 7,854 91% 5,000 2,200 7,200\nOropharynx 21,474 70% 2,300 12,900 15,200\nTOTAL 47,984 79% 21,800 16,000 37,800\n*Estimates were rounded to the nearest 100. Estimated counts might not sum to total because of rounding.\n**Includes anal and rectal squamous cell carcinomas\nSources: https://www.cdc.gov/cancer/hpv/cases.html  and http://www.cdc.gov/cancer/dataviz16\n0102030405060708090100\n2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 2021 2022 2023Percent Vaccinated\nSurvey Year≥1 HPV (females, 79%)\n≥1 HPV (males, 75%)\nHPV UTD (females, 64%)\nHPV UTD (males, 59%)≥1 Tdap\n≥1 MenACWYHPV vaccination  \nrecommendation\n for malesEstimated vaccination coverage, adolescents aged 13 –17 years, \nNational Immunization Survey -Teen, United States, 2006 –2023\nUTD: up -to-date\nPingali C, Yankey  D, Chen M,  et al. MMWR. 2024;73(33):708 -714.HPV vaccination  \nrecommendation\nfor females\n17\nQuadrivalent HPV vaccine -type prevalence declined 85% \namong 14 –24-year -old sexually experienced females\n18.5\n2.8\n0510152025\n2003 –2006  (prevaccine era) 2007 –2010 2011 –2014 2015 –2018Quadrivalent type prevalence, %85% \nDecline\nRosenblum HG, Lewis RM, Gargano JW, Querec TD, Unger ER, Markowitz LE. Ann Intern Med. 2022;175(7):918 -926. 18\nStefanos R, Lewis RM, Querec TD, Gargano JW, Unger ER, Markowitz LE. Hum Vaccin  Immunother . 2024;20(1):2308378.0510152025\nWhite, non-Hispanic Black, non-Hispanic Mexican AmericanQuadrivalent type prevalence, %2003 –2006 2015 –2018\n82% 86%Quadrivalent HPV vaccine -type prevalence declined  >80% \namong 14 –24-year -old sexually experienced females in \ndifferent racial/ethnic groups\n100%\n19\nEstimated number of cervical precancer (CIN2+) cases per \nyear, United States, 2008 and 2016\nError bars indicate range of low and high estimates based on lower -incidence and higher -incidence sites.\nMcClung NM, Gargano JW, Park IU, et al. MMWR. 2019;68(15):337 -343.20\nCIN2+ and CIN3+ declined in young women, HPV -IMPACT,* \n2008 –2022\n2102004006008001000120014001600\n2008\n2009\n2010\n2011\n2012\n2013\n2014\n2015\n2016\n2017\n2018\n2019\n2020\n2021\n2022Incidence per 100,000\nYearCIN2+ \n20–24-year -olds observed 25–29-year -olds observed 20–24-year -olds modeled 25–29-year -olds modeled\n*HPV -IMPACT: Human Papillomavirus Vaccine Impact Monitoring Project  https://www.cdc.gov/hpv -impact/about/index.html\nGargano JW, Stefanos R, Dahl RM, et al. MMWR. 2025;74(6):96 -101.02004006008001000120014001600\n2008\n2009\n2010\n2011\n2012\n2013\n2014\n2015\n2016\n2017\n2018\n2019\n2020\n2021\n2022Incidence per 100,000\nYearCIN2+ per 100,000 screened women \nCIN2+ includes grades 2 or worse and adenocarcinoma in situ.050100150200250300350400450\n2008\n2009\n2010\n2011\n2012\n2013\n2014\n2015\n2016\n2017\n2018\n2019\n2020\n2021\n2022Incidence per 100,000\nYearCIN3+ per 100,000 screened women \nCIN3+ includes grade 3 and adenocarcinoma in situ.\nCervical cancer declined in young women, United States \nCancer Statistics, 1999 –2017\nAge 21 -24 years\nSCC: squamous cell carcinoma\nMix JM, Van Dyne EA, Saraiya M, Hallowell BD, Thomas CC. Cancer Epidemiol Biomarkers Prev. 2021;30(1):30 -37. 22\nEstimated costs of HPV -attributable disease\n23Clay PA, Thompson TD, Markowitz LE, Ekwueme DU, Saraiya M, Chesson HW. Vaccine. 2023;41(14):2376 -2381.•CDC estimated annual direct medical costs of HPV -attributable disease \nin 2020 US dollars, published in 2023.\n•Annual total cost of HPV -attributable disease is $9.01 billion. \n•Annual total cost due to treatment is $4.05 billion.\n•37,800 HPV -attributable cancers are diagnosed in the US annually.\n•HPV vaccination coverage lags behind other adolescent vaccinations.\n•HPV vaccination has led to decreases in infection prevalence and \ncervical precancer incidence, and there are early signs that vaccination \nhas decreased cervical cancer incidence in young women.\n•Total cost of HPV -related disease is $9.01 billion.Summary: Public Health Problem\n24\nPublic Health Problem : Work Group Interpretation\nIs HPV -related disease of public health importance?\nNo Probably No Probably Yes Yes Don’t Know Varies\n25\nBenefits and Harms\nHow substantial are the desirable anticipated effects of changing the wording of the age for routine \nvaccination to 9 –12 years ?\nHow substantial are the undesirable anticipated effects of changing the wording of the age for routine \nvaccination to 9 –12 years ?\nDo the desirable  effects outweigh the undesirable effects of changing the wording of the age for routine \nvaccination to 9 –12 years ? \n26\nPotential benefits and harms\nBenefits\n•Clarity\n•Flexibility  Harms\n•Separation from adolescent platform\n•Prompts at age 9 may not be acceptable \nto some providers\n27\nBenefit: Wording change would increase clarity\nHPV vaccination is routinely recommended at age 9 –12 years\n  instead of\nHPV vaccination is routinely recommended at age 11 or 12 years; \nvaccination can be given starting at age 9 years\n28\nBenefit: Wording change may increase flexibility for \nproviders who would like to vaccinate at age 9\n•Some partners are interested in vaccination at age 9\n•9–12 wording would change Clinical Decision Support for Immunization \n(CDSi ) resources and may increase flexibility for providers who are \ninterested in vaccination at age 9\n29\nCDSi  implications\n•If change adopted:\n•Minimum age: 9 years\n•Earliest recommended age: 9 years\nPrompt for HPV vaccination occurs at \nearliest recommended age (9 years)•Current:\n•Minimum age: 9 years\n•Earliest recommended age: 11 years\nPrompt for HPV vaccination occurs at \nearliest recommended age (11 years)\n30 https://www.cdc.gov/iis/cdsi/index.html\n31 Notes and full schedule available at: https://www.cdc.gov/vaccines/hcp/imz -schedules/child -adolescent -age.htmlVaccine Birth 1 \nmo2 \nmos4 \nmos6 \nmos9 \nmos12 \nmos15 \nmos18 \nmos19–\n23 \nmos2–3 \nyrs4–6 \nyrs7–10 yrs 11–\n12 \nyrs13–\n15 \nyrs16 \nyrs17–\n18 \nyrs\nHPVSee \nnotes\nRange of \nrecommended \nages for all \nchildrenRange of \nrecommended \nages for catch-\nup vaccinationRange of \nrecommended \nages for \ncertain high-\nrisk groupsRecommended \nvaccination can \nbegin in this age \ngroupRepresentation of HPV vaccination recommendations on \nTable 1 of the child and adolescent i mmunization schedule\n32Vaccine Birth 1 \nmo2 \nmos4 \nmos6 \nmos9 \nmos12 \nmos15 \nmos18 \nmos19–\n23 \nmos2–3 \nyrs4–6 \nyrs7–10 yrs 11–\n12 \nyrs13–\n15 \nyrs16 \nyrs17–\n18 \nyrs\nHPV\nRange of \nrecommended \nages for all \nchildrenRange of \nrecommended \nages for catch-\nup vaccinationRange of \nrecommended \nages for \ncertain high-\nrisk groupsRecommended \nvaccination can \nbegin in this age \ngroupSee notesPotential representation of HPV vaccination recommendations \non Table 1 of the child and adolescent i mmunization schedule\nPolicy question is changing the wording of recommended age \nto 9–12 and not changing the recommended age to 9 –10\n•Age 9 Systematic Review*: \n-Higher vaccination series completion by age 13** when initiating at age 9 –10 vs. \n11–12, but study limitations preclude a cause -and-effect interpretation.\n-A small percentage of vaccinated adolescents had initiated at age 9 –10 in most \nstudies (2 –8%).\n-There may be differences between families/providers vaccinating at age 9 –10 and \nthose vaccinating at age 11 –12.\n-Due to multi -pronged interventions in QI studies, it is unclear if the component \nfocused on initiation at ages 9 –10 was responsible for increases in coverage.\n*https://www.cdc.gov/acip/downloads/slides -2024 -10-23-24/04 -hpv-Brewer -508.pdf\n**Some studies evaluated completion, but not by age 13 years 33\nHarm: Wording change may affect adolescent platform\n34•Adolescent platform was established in 1996\n•HPV was licensed and recommended in 2006 as part of the adolescent \nplatform\n•Adolescent platform (11 –12 years): HPV, Tdap, and MCV \nSimultaneous administration of HPV vaccine with other \nrecommended vaccines among adolescents aged 13 –17 \nyears who initiated HPV vaccine (N=12,995) — NIS-Teen, \nUnited States, 2023\nVaccinations in a single visit n Weighted %* (95% CI)\nReceived HPV vaccine only 3,874 30.5 (29.0 -32.1)\nReceived HPV vaccine and one or more vaccine (s) \n(Tdap, MenACWY , and/or flu vaccine)9,121 69.5 (67.9 -71.0)\nReceived Tdap and MenACWY  and HPV vaccines 6,579 47.8 (46.0 -49.5)\nNIS-Teen: National Immunization Survey -Teen\n*Percentages were calculated among only those adolescents who initiated the HPV vaccine (12,995)35\n•1,047 primary care professionals surveyed on perceived advantages and \ndisadvantages of recommending HPV vaccine at age 9:\n-Most commonly perceived disadvantage of recommending vaccination at age 9 \nwas parents’ lack of readiness (73%). \n•2,527 primary care providers and clinical staff randomly assigned to \nconsider the perceived benefits of HPV vaccination at age 9 versus age 12:\n-Providers were less likely to identify “parents ready to talk about HPV vaccine” as \na perceived benefit for vaccination at age 9 vs. age 12.Harm: Wording change may lead to system changes that are \nnot acceptable to some providers\n36Kong WY , Huang Q, Thompson P , Grabert  BK, Brewer NT, Gilkey MB. Acad  Pediatr . 2022;22(4):573 -580.\nKahn BZ, Reiter PL, Kritikos  KI, Gilkey MB, Queen TL, Brewer NT. Hum Vaccin  Immunother . 2023;19(1):2172276.\n•Changing the wording of the age for routine vaccination to 9 –12 may provide clarity \nand flexibility to support those providers who are interested in vaccination at age 9.\n-Vaccination at ages 9 –10 years is associated with increases in completion by age 13* but due \nto limitations in studies, it is unclear if this association is causal.\n-QI/Intervention studies have found increases in initiation at all ages and increased \ncompletion but unclear contribution of vaccination at ages 9 –10 due to multiple \ninterventions implemented simultaneously.\n•48% of adolescents receive the HPV vaccine as part of the adolescent platform and \n70% receive it with one or more vaccines; changing the wording of the age for \nroutine vaccination may negatively affect the adolescent platform.\n•Changing the wording to 9 –12 may lead to system changes or prompts to providers \nfor vaccination at age 9 which some may not find acceptable.Summary: Benefits and Harms \n*Some studies evaluated completion, but not by age 13 years 37\nBenefits and Harms : Work Group Interpretation\nHow substantial are the desirable  anticipated effects of changing the wording of the \nage for routine vaccination to 9 –12 years ?\nHow substantial are the undesirable  anticipated effects of changing the wording of \nthe age for routine vaccination to 9 –12 years ?\n38Don’t Know Minimal Small Moderate Large Varies\nMinimal Small Moderate Large Don’t Know Varies\nBenefits and Harms : Work Group Interpretation\nDo the desirable  effects outweigh the undesirable  effects of changing the \nwording of the age for routine vaccination to 9 –12 years ? \n39Favors change \nin wordingFavors current \nwordingFavors both wording \noptions equallyDon’t Know Varies\nAcceptability/Values\n40Is changing the wording of the age for routine vaccination to 9 –12 years acceptable to key stakeholders \n(e.g., providers, professional societies, or advocacy groups)?\nDo parents feel that the desirable effects of changing the wording to 9 –12 are large relative to the \nundesirable effects of changing the wording?\nIs there important uncertainty about, or variability in, how much parents value changing the wording to \n9–12?\nAmerican Academy of Pediatrics Recommendations\nBeginning in the 2018 –2021 Red Book , HPV vaccination recommendation language \nwas modified.\n \n“The AAP recommends starting the series between the ages of 9 and 12 years, at an \nage that the pediatric health care professional deems optimal for acceptance and \ncompletion of the vaccination series.” \nAmerican Academy of Pediatrics. Red Book: 2024 -2027 Report of the Committee on Infectious Diseases (33rd Edition) 41\nHPV Vaccination Roundtable and American Cancer Society\nhttps://hpvroundtable.org/\nhttps://hpvroundtable.org/wp -content/uploads/2023/05/2021 -HPV -VACs -Impact -Report.pdf\nFoley S, Nkonga  J, Fisher -Borne M. Hum Vaccin  Immunother . 2023;19(1):2167906.\n•The National HPV Vaccination Roundtable is a \ncoalition of about 90 organizations. \n•The National HPV Vaccination Roundtable has \nencouraged providers to vaccinate at age 9 years.\n42\nAdolescent medicine stakeholder comments\nAdolescent Immunizations: A Position Paper of the Society for Adolescent Medicine: \n“The development of three distinct adolescent vaccination visits/platforms for adolescents (11 –12-\nyear visit, 14 –15-year visit, and a 17 –18-year visit) to integrate and emphasize the role of \nvaccination in already recommended comprehensive health care screening and provision visits. The \n11–12-year platform is the primary immunization platform promulgated by ACIP .”\nPotential Changes to the Adolescent Immunization Schedule:  Implications for the Stability of \nAdolescent Immunization Platform Visits: \n“Moving HPV vaccination to ages 9 –10years weakens the established platform…which could \nunintentionally result in lower adolescent vaccination rates overall.”\nMiddleman AB, Rosenthal SL, Rickert VI, et al. J Adolesc  Health. 2006;38(3):321 -327.\nMiddleman AB, Zimet  GD. J Adolesc  Health . 2024;75(4):538 -542. 43\n2 Clinician Interviews :\n-1 intervention study: providers/nurses reported a positive experience with \nrecommending vaccination at age 9 –10 \n-1 qualitative study: providers/staff had mixed opinions on initiating at age 9\n3 Clinician Surveys :\n-1 survey: among those not currently recommending at age 9, 61% willing to do so \n-1 survey: strong provider recommendations differed by age group of patient and \nspecialty of provider\n-1 survey: provider recommendation at age 9 depended on recommendation framingSummary: provider behavior/perspective studies (N=5)\n44Biancarelli  DL, Drainoni  ML, Perkins RB. J Pediatr . 2020;217:92 -97.\nVielot  NA, Lane RM, Loefstedt  K, et al. Pilot Feasibility Stud. 2023;9(1):153.\nKong WY , Huang Q, Thompson P , Grabert  BK, Brewer NT, Gilkey MB. Acad  Pediatr . 2022;22(4):573 -580.\nLake P , Fuzzell  L, Brownstein NC, et al. Hum Vaccin  Immunother . 2023;19(1):2181610.\nKahn BZ, Reiter PL, Kritikos  KI, Gilkey MB, Queen TL, Brewer NT. Hum Vaccin  Immunother . 2023;19(1):2172276.\n2 Caregiver Studies:\n-Few caregivers reported receiving information or recommendations to vaccinate \nchildren before age 11.\n-Most reported willingness to vaccinate at ages 9 –10.Summary: caregiver behavior/perspective studies (N=2)\nAragones  A, Gany  F, Kaplan A, Bruno D. Hum Vaccin  Immunother . 2022;18(6):2136444.\nKohler RE, Wagner RB, Careaga  K, Btoush  R, Greene K, Kantor L. Hum Vaccin  Immunother . 2023;19(3):2270842. 45\nSummary: Acceptability/Values\n•AAP recommendation language uses ages 9 –12.\n•Some stakeholders/advocacy groups are interested in vaccination at \nage 9 and changing the wording will clarify that vaccination at age 9 is \nconsistent with ACIP recommendations.\n•Some stakeholders have raised concerns that changing the wording will \nerode the adolescent platform.\n•In limited number of studies, vaccination at ages 9 –10 years was \nacceptable to providers and parents.\n46\nAcceptability : Work Group Interpretation\nIs changing the wording of the age for routine vaccination to 9 –12 \nyears acceptable to key stakeholders (e.g., providers, professional \nsocieties, or advocacy groups)?\n47No Probably No Probably Yes Yes Don’t Know Varies\nValues: Work Group Interpretation\nDo parents feel that the desirable effects of changing the wording to 9 –12 are large \nrelative to the undesirable effects of changing the wording?\nIs there important uncertainty about, or variability in, how much parents value \nchanging the wording to 9 –12?\n48No Probably No Probably Yes Yes Don’t Know Varies\nNo important uncertainty or variabilityImportant uncertainty or variability\nProbably important uncertainty or variability\nProbably not important uncertainty or variability\nNo known undesirable outcomesMinority opinion\nPlurality opinion\nEvidence to Recommendations ( EtR) Framework\nEtR Domain Question\nPublic Health ProblemIs the problem of public health importance?\nBenefits and HarmsHow substantial are the desirable anticipated effects?\nHow substantial are the undesirable anticipated effects?\nDo the desirable effects outweigh the undesirable effects?\nAcceptability/ValuesIs the intervention acceptable to key stakeholders?\nDoes the target population feel that the desirable effects are large relative to \nundesirable effects?\nIs there important uncertainty about or variability in how much people value the \nmain outcomes?\nResource UseImpact on cost -effectiveness will likely be minimal.\nEquityWhat would be the impact on health equity?\nFeasibilityIs the intervention feasible to implement?\n49\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position \nof the Centers for Disease Control and Prevention.\nAcknowledgements\n50Sarah Brewer, PhD, MPH\nCarla DeSisto, PhD, MPH\nJulia Gargano, PhD\nLauri Markowitz, MD", "summary": "Evidence to Recommendations Framework Wording of the age for routine HPV vaccination Ruth Stefanos, MD, MPH Advisory Committee on Immunization Practices April 15, 2025National Center for Immunization and Respiratory Diseases 1 Current recommendation https://www.cdc.gov/acip -recs/hcp/vaccine -specific/hpv.html•HPV vaccination is routinely recommended at age 11 or 12 years •Vaccination can be given starting at age 9 years •Since 2006 (first ACIP recommendation), the wording of age at HPV …", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/06-Stefanos-HPV-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 50}
{"title": "07 Markowitz HPV 508", "content": "ACIP HPV Vaccines Work Group\nNext steps\nLauri E. Markowitz, MD\nCo-Lead, ACIP HPV Vaccines Work GroupNational Center for Immunization & Respiratory Diseases\nAdvisory Committee on Immunization Practices \nApril 15, 2025\n▪Wording of the recommendation for age at routine HPV vaccination\n▪Number of doses in the recommended HPV vaccination seriesQuestions being considered by ACIP HPV Vaccines WG\n2\nWording of the age for routine HPV vaccination\nOctober 2024 ACIP meeting \n▪Introduction and historical context\n▪Review of data regarding programmatic aspects of vaccination at age 9 –10 \ninstead of 11 –12 years – no strong evidence of benefit\n▪Plan: modify wording of the routine age recommendation to 9 –12 years . \nApril 2025 ACIP meeting\n▪EtR framework for changing wording to state that routine vaccination is \nrecommended at age 9 –12 years (part 1)\nJune 2025 ACIP meeting\n▪EtR framework for changing wording to state that routine vaccination is \nrecommended at 9 –12 years (part 2)ACIP HPV Vaccines WG, past and next steps\n3\nNumber of doses in the recommended HPV vaccination series\nOctober 2024 ACIP meeting \n▪Introduction\n▪Review of main studies providing evidence for reducing the number of doses\n▪Status of global adoption of HPV vaccination \nApril 2025 ACIP meeting \n▪Updated review of data, KEN -SHE, U.S. HPV vaccination coverage, modeling\nJune 2025 ACIP meeting \n▪Data from ESCUDDO\n▪Additional data and information requested by ACIP\n▪EtR framework\nPlan for ACIP votes on both questions at the same meeting (June 2025)ACIP HPV Vaccines WG, past and next steps\n4\nTrial\nGirls 12–16 years old\n(n=20,300)\nBivalent\n(n=10,150)9-valent\n(n=10,150)\nActive Follow -up \nCervical cells, blood, urine at M12, M18, M24, M30, M36, M42, \nM48, M54, M60M0: Randomized to vaccine\nM6: Randomized to dosing \nschedule\n1 Dose 2 Doses 1 Dose 2 DosesEpidemiologic Surveys\n(unvaccinated)\nHPV infection status\nM0 and M6\nHPV vaccine\nESCUDDO, Costa Rica (data available June 2025)\n▪Randomized trial to evaluate non -inferiority of one vs two doses of 2vHPV (Cervarix) and 9vHPV \n(Gardasil 9) for prevention of new cervical HPV16/18 infections that persist at least 6 months\n▪Evaluate one dose compared to zero doses\nClinicalTrials.gov: NCT031800345\n▪Longer term duration of efficacy and immunogenicity of 1 dose\n-Longest efficacy data = IARC -India (15 years)\n-Longest immunogenicity data = Costa Rica Vaccine Trial (16 years)\n▪Protection at sites other than the cervix\n-No data on protection at sites other than the cervix\n▪Efficacy and immunogenicity of 1 dose in males\n-No efficacy data in males\n-Some evidence of lower antibody levels in adolescent males versus females \nafter 1 doseOutstanding questions for number of doses \n6\n▪Merck announced plans for 1 -dose HPV vaccination evaluation in March 2024*\n▪Two international, randomized, double -blind, efficacy clinical trials are planned, \none in males (16 –26 y) and one in females (16 –26 y)\n▪Planned trials include elements that regulators have deemed necessary\n-Evaluate other endpoints besides persistent cervical infection \n-Conduct one study in males and one study in females\n-Compare 1 -dose efficacy vs. 3 -dose efficacy \n-Assess duration of protection\n▪Since 2024 to present - Merck has been in discussions with FDA and EMA \nregarding trial design\n-Regulatory feedback anticipated in 2Q2025Merck clinical program updates\n*Merck Announces Plans to Conduct Clinical Trials of a Novel Investigational Multi -Valent Human Papillomavirus (HPV) Vaccine and  Single -Dose Regimen for GARDASIL®9 EMA, European Medicines Agency\n7\n▪An ACIP recommendation for 1 -dose vaccination at any age or 2-dose \nvaccination for persons aged ≥15 years would be off -label\n▪Off-label recommendations \n•Anything that is not stated in the package insert \n•Something different than is explicitly stated in the package insert\n•Manufacturers can only promote and educate on licensed FDA indications\n▪At least 46 licensed vaccine products have some off -label ACIP \nrecommendationNumber of doses in the recommended HPV vaccination series\n8\n▪Age outside of licensed age range\n-Hemopoietic stem cell transplant patients & other special groups (several)\n-Travelers or special situations (e.g., MMR and hepatitis A vaccine)\n-Catch -up or shared clinical decision -making (e.g., Tdap and MenABCWY )\n▪Modified dosing schedules\n-Immunocompromising conditions (hepatitis B vaccine) \n-Standard recommendation is 2 -dose instead of 3 -dose schedule (rabies vaccine \npre-exposure)\n▪Inactivated influenza vaccine use with egg allergy \n▪Tdap use in pregnancy\n-No longer off -label but was for over 10 yearsOff-label ACIP recommendations - examples\n9\nOptions being discussed by the ACIP HPV Vaccines WG \nfor modification to the current recommendations \nExpanding a 2-dose recommendation \nfrom 9–14 years to 9 –26 years, or \nthrough an older age  Recommending 1 dose for 9–14 years, \n9–20 years or through another age2 doses 1 dose \nNote: No discussion about changing the 3 -dose recommendation for persons with immunocompromising conditions\n    10\n▪2 doses for 9 –26 years; 3 doses for 27 –45 years, or\n▪2 doses for 9 –45 yearsPossible revised recommendations –expansion of  \n2-dose recommendation \nNote: No discussion about changing the 3 -dose recommendation for persons with immunocompromising conditions\n    11\n▪1 dose for 9 –14 years; 3 doses for 15 –45 years\n▪1 dose for 9 –14 years; 2 doses for 15 –45 years\n▪1 dose for 9 –14 years; 2 doses for 15 –26 years; 3 doses for 27 –45 years\n▪1 dose for 9 –20 years; 3 doses for 21 –45 years\n▪1 dose for 9 –20 years; 2 doses for 21 –45 years\n▪1 dose for 9 –20 years; 2 doses for 21 –26 years; 3 doses for 27 –45 years\n▪1 dose for 9 –26 years; 3 doses for 27 –45 years\n▪1 dose for 9 –26 years; 2 doses for 27 –45 yearsPossible revised recommendations –including 1 -dose\nNote: No discussion about changing the 3 -dose recommendation for persons with immunocompromising conditions\n    12\n▪All Work Group members are in favor of some change to the number of doses \nin the HPV vaccination schedule \n▪Work Group members have different opinions about expanding the 2 -dose \nschedule and/or recommending 1 dose in some age groups\n▪Work Group continues to review data and discuss the upper age range if \nthere is a 1 -dose recommendation and/or if the 2 -dose schedule is expanded \nbeyond age 9 –14 yearsDiscussion by Work Group members\n13\nDoes ACIP have any questions or comments regarding the policy \nquestions to be addressed?\nWhat additional information would ACIP like to see before potentially \nvoting at the next meeting?Questions for ACIP\n14\nFor more information, contact CDC\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position \nof the Centers for Disease Control and Prevention.\nThank you", "summary": "ACIP HPV Vaccines Work Group Next steps Lauri E. Markowitz, MD Co-Lead, ACIP HPV Vaccines Work GroupNational Center for Immunization & Respiratory Diseases Advisory Committee on Immunization Practices  April 15, 2025 ▪Wording of the recommendation for age at routine HPV vaccination ▪Number of doses in the recommended HPV vaccination seriesQuestions being considered by ACIP HPV Vaccines WG 2 Wording of the age for routine HPV vaccination October 2024 ACIP meeting  ▪Introduction and historical…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/07-Markowitz-HPV-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 15}
{"title": "01 Jamieson cytomegalovirus 508", "content": "ACIP Cytomegalovirus (CMV) Vaccines Workgroup\nIntroduction\nDenise Jamieson, MD\nChair, CMV Vaccines Workgroup\nApril 15th, 2025National Center for Immunization & Respiratory Diseases\n\nACIP Members\n•Denise Jamieson (WG chair)\n•Bonnie Maldonado\nLiaisons\n•David Kimberlin (AAP)\n•Liat Greenwood Chernoff (ACNM)\n•Naima Joseph (ACOG)\n•Tabitha Hanson (AIM)\n•Leisha Nolen (CSTE)\n•Ajit Limaye (IDSA)\n•Caleb Lyu (NACCHO)\n•Maria Carrillo -Marquez (PIDS)ACIP CMV WG Members\nEx Officio Members\n•Douglas Pratt (FDA)\n•Britt Rizek  (HRSA)\n•Matthew Clark (IHS)\nConsultants\n•Andrea Ciaranello (Harvard Medical School)\n•Rana Chakraborty (University of Miami)\n•Sonja Rasmussen (Johns Hopkins University)\n•Martina Badell (SMFM)\nCDC Staff - DVD\n•Tatiana Lanzieri (WG co -lead)\n•David Sugerman (WG co -lead)\nCDC Staff - DVD\n•Tom Clark (ACIP advisor)\n•Sara Oliver (ACIP advisor) \n•Dan Filardo\n•Jessica Leung\n•Chelsea Lutz\n•Lois Park\n•Kelley Raines\n•Ashrita Rau\n•Brian WakemanACIP CMV WG CDC Participants\nCDC Staff - non-DVD\n•Amimah  Asif (ISD)\n•Karen Pazol  (ISD)\n•Christine Olson (ISO)\n•Elizabeth Quincer  (ISO)\n•Kate Woodworth (DBDID)\n•Alison Fountain (DBDID)\n•Naomi Tepper (DRH)\nACIP Staff\n•Melinda Wharton\n•Jessica MacNeil\n•Leslie Lee\n•Stephanie Thomas\na.CMV and congenital CMV (cCMV) epidemiology and \ndisease burden \nDr. Tatiana Lanzieri (WG co -lead)\nb.CMV vaccine safety and immunogenicity data\nDr. Robert Paris (Moderna)\nc.Initial work group considerations for CMV vaccine policy \nDr. Tatiana Lanzieri\nd.DiscussionACIP CMV Vaccines Workgroup", "summary": "ACIP Cytomegalovirus (CMV) Vaccines Workgroup Introduction Denise Jamieson, MD Chair, CMV Vaccines Workgroup April 15th, 2025National Center for Immunization & Respiratory Diseases  ACIP Members •Denise Jamieson (WG chair) •Bonnie Maldonado Liaisons •David Kimberlin (AAP) •Liat Greenwood Chernoff (ACNM) •Naima Joseph (ACOG) •Tabitha Hanson (AIM) •Leisha Nolen (CSTE) •Ajit Limaye (IDSA) •Caleb Lyu (NACCHO) •Maria Carrillo -Marquez (PIDS)ACIP CMV WG Members Ex Officio Members •Douglas Pratt…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/01-Jamieson-cytomegalovirus-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 4}
{"title": "02 Lanzieri cmv 508", "content": "ACIP CMV Vaccine Workgroup\nCytomegalovirus (CMV) and congenital CMV (cCMV) \nEpidemiology and Disease Burden\nTatiana M. Lanzieri, MD, MPH\nACIP CMV WG Co -Lead\nApril 15th, 2025\nMeasles, Rubella and CMV Epidemiology TeamViral Vaccine Preventable Diseases BranchDivision of Viral DiseasesNational Center for Immunization & Respiratory Diseases\n\nReview epidemiology and disease burden of CMV and cCMVObjectives\nMore than 16,000 children born with cCMV infection in \nthe U.S. every year – 4.5 per 1,000 live births\nFrequencies based on unpublished review of 30 unique cohorts of children with cCMV  identified through newborn screening followed up through childhood.OutcomeAnnual \nnumber of \naffected \nchildren%\nNeonatal death 80 0.5\ncCMV disease† 2800 17\nLong -term outcomes (selected)\nSensorineural hearing loss 825 5\nCognitive impairment 495 3\nMotor impairment 165 1\n\nNeonatal signs\nRash (purpura/petechiae)\nEnlarged liver and/or spleen (hepatosplenomegaly)\nSmall head (microcephaly)\nLaboratory diagnosis\nPCR or culture positive on urine, blood, cerebrospinal \nfluid collected within 21 days of life\nMost newborns with cCMV infection have no \nclinical signs at birth and are not diagnosedcCMV disease\nCongenital Cytomegalovirus ( cCMV ) Infection and Disease 2024 Case Definition | CDC\nUS landscape on cCMV screening and surveillance\nME\nWI VT NH\nND MN IL MI NY MA WA ID MT\nSD IA IN OH PA NJ CT RI OR NV WY\nNE MO KY WV VA MD DE CA UT CO\nKS AR TN NC SC AZ NM\nOK LA MS AL GA AK\nTX FL HIcCMV  surveillance (n=13)\nUniversal screening (n= 2)\nTargeted -hearing screening (n= 11)\nSymptom- based screening (n=3)\nLast updated February 2025\nState -specific cCMV prevalence estimates, United States\nAdapted from Lutz et al. Updated National and State -Specific Prevalence of Congenital Cytomegalovirus Infection, United States, 2018- 2022. J Public Health Manag  Pract . 2024cCMV  infection prevalence (per 1,000 live births)\nCMV IgG Seroprevalence, United States\nNational Health and Nutrition Examination Surveys (NHANES)\n213642495464\n293843505758\n0255075\n1-5 6-11 12-19 20-29 30-39 40-49CMV prevalence (%)\nAge (years)\nLanzieri et al. Seroprevalence of cytomegalovirus among children 1 to 5 years of age in the United States from the National H ealth and Nutrition Examination \n     Survey of 2011 to 2012. Clin Vaccine Immunol 2015\nLanzieri et al. Cytomegalovirus Seroprevalence Among US Children Aged 1 to 5 Years: The National Health and Nutrition Examina tion Surveys, 2017- March 2020 \n     Pre -Pandemic Dataset. Clin Infect Dis 2022\nBate et al. Cytomegalovirus seroprevalence in the United States: the national health and nutrition examination surveys, 1988 -2004. Clin Infect Dis 2010Increase with older age\nPersons 6- 49 years: \nNo significant changes from \n1988- 1994 to 1999-2004\nChildren 1 -5 years: \nIncreased from 21% to 29% between 2011 -2012 and 2017- 2020 \npre-pandemic1988- 1994\n1999- 20042011- 2012\n2017- 2020NHANES cycles\nCMV IgG Seroprevalence, United States, \nNHANES, 1999 -2004*\n0255075100\n1-5 6-11 12-19 20-29 30-39 40-49CMV prevalence (%)\nAge (years)Non -Hispanic Black females\nHispanic females\nNon -Hispanic White females\n*Except for 1 -5 years (2017- 2020 pre -pandemic dataset)\nLanzieri et al. Cytomegalovirus Seroprevalence Among US Children Aged 1 to 5 Years: The National Health and Nutrition Examina tion Surveys, 2017- March 2020 Pre -Pandemic Dataset. \nClin Infect Dis 2022\nBate et al. Cytomegalovirus seroprevalence in the United States: the national health and nutrition examination surveys, 1988 -2004. Clin Infect Dis 2010\nCMV IgG Seroprevalence, United States, \nNHANES, 1999 -2004*\n0255075100\n1-5 6-11 12-19 20-29 30-39 40-49CMV prevalence (%)\nAge (years)Non -Hispanic Black females\nHispanic females\nNon -Hispanic White females\n*Except for 1 -5 years (2017- 2020 pre -pandemic dataset)\nLanzieri et al. Cytomegalovirus Seroprevalence Among US Children Aged 1 to 5 Years: The National Health and Nutrition Examina tion Surveys, 2017- March 2020 Pre -Pandemic Dataset. \nClin Infect Dis 2022\nBate et al. Cytomegalovirus seroprevalence in the United States: the national health and nutrition examination surveys, 1988 -2004. Clin Infect Dis 201036%77%81%\n20-29\nRisk of vertical transmission and cCMV disease according \nto timing and type of maternal infection\nTransmission rate \n(%)Symptomatic at \nbirth* (%)SNHL or \nneurodevelopmental \nabnormality* (%)\nPrimary infection †\nPericonception 21.0 1.3 -\nFirst trimester 36.8 9.1 22.8\nSecond trimester 40.3 0.3 0.1\nThird trimester 66.2 0.4 0.0\nNon -primary infection 3.4§3 of 7§§3 of 7§§\nChatzakis  et al. Timing of primary maternal cytomegalovirus infection and rates of vertical transmission and fetal consequences. AJOG 2 020\nSimonazzi et al. Perinatal outcomes of non -primary maternal CMV infection: a 15 -year experience. Fetal Diagn  Ther  2017.†Primary maternal infection in CMV -seronegative women was defined as seroconversion or low avidity IgG; pooled rates of \nvertical transmission following primary maternal infection from 10 studies, 2942 fetuses\n*Pooled rates of cCMV disease from 10 studies, 796 infected fetuses\n§ Transmission rate from 1 study including 205 pregnant women diagnosed with non- primary infection\n§§ Sample too small, 6 in the first trimester and 1 unknown timing\n10\nRisk of vertical transmission and cCMV disease according \nto timing and type of maternal infection\nTransmission rate \n(%)Symptomatic at \nbirth* (%)SNHL or \nneurodevelopmental \nabnormality* (%)\nPrimary infection †\nPericonception 21.0 1.3 -\nFirst trimester 36.8 9.1 22.8\nSecond trimester 40.3 0.3 0.1\nThird trimester 66.2 0.4 0.0\nNon -primary infection 3.4§3 of 7§§3 of 7§§\nChatzakis  et al. Timing of primary maternal cytomegalovirus infection and rates of vertical transmission and fetal consequences. AJOG 2 020\nSimonazzi et al. Perinatal outcomes of non -primary maternal CMV infection: a 15 -year experience. Fetal Diagn  Ther  2017.†Primary maternal infection in CMV -seronegative women was defined as seroconversion or low avidity IgG; pooled rates of \nvertical transmission following primary maternal infection from 10 studies, 2942 fetuses\n*Pooled rates of cCMV  disease from 10 studies, 796 infected fetuses\n§ Transmission rate from 1 study including 205 pregnant women diagnosed with non- primary infection\n§§ Sample too small, 6 in the first trimester and 1 unknown timing\n11\nIncidence of CMV primary infection and reinfection varies \nacross populations\nCountryAnnual rate\nPopulation \n(Assessment)Primary (PI)\nIgG seroconversionReinfection (R)\nIgG seroconversion \nto new CMV strains \nUS 0.4-7% 10%PI: pregnant women, IgG seroconversion, low IgG avidity or viral \nshedding in clinical trials and other studies (1,2,3,4)\nR: post -partum women, IgG seropositive with seroconversion to new \nstrains (5)\nBrazil 20% 9-35%Pregnant women, IgG seronegative during 1st trimester or seropositive \nat first prenatal visit (6,7)\nR: range for non -transmitters vs. transmitters mothers\n1 Hughes et al. A Trial of Hyperimmune Globulin to Prevent Congenital Cytomegalovirus Infection. N Engl J Med 2021\n2 Hyde et al. Cytomegalovirus seroconversion rates and risk factors: implications for congenital CMV. Rev Med Virol 2010\n3 Colugnati et al. Incidence of cytomegalovirus infection among the general population and pregnant women in the United States. BMC Infec t Dis 2007\n4 Das et al. Safety, efficacy, and immunogenicity of a replication -defective human cytomegalovirus vaccine, V160, in cytomegalov irus-seronegative women: a double -blind, randomised , \n     placebo -controlled, phase 2b trial. Lancet Infect Dis 2023\n5 Ross et al. Cytomegalovirus reinfections in healthy seroimmune  women. JID 2010\n6 Mussi -Pinhata  et al. Seroconversion for cytomegalovirus infection during pregnancy and fetal infection in a highly seropositive population:  “the BraCHS  study.” JID 2018\n7 Yamamoto et al. Human cytomegalovirus reinfection is associated with intrauterine transmission in a highly cytomegalovirus -imm une maternal population. AJOG 2010\nProportions of cCMV  infections due to non- primary maternal infection (NPI)  \nvary with maternal seroprevalence but risk of cCMV  infection is higher when \nmother is CMV seronegative before pregnancy\nCountry, years \n(n° infants screened)Maternal \nCMV IgG \nseroprevalencecCMV infection \nprevalence\nper 1,000 live birthsRisk of cCMV \namong seronegative \nvs. seropositive \nmotherProportion \nattributable to NPI\nFrance, 2013- 2015\n(12,000)61% 3.70.86% vs. 0.2% \n(4x)52%\nBrazil, 2013- 2017 \n(12,000)97% 5.72.8% vs. 0.5% \n(6x)90%\nLeruez -Ville  et al. Risk Factors for Congenital CMV Infection Following Primary and Nonprimary Maternal Infection: A Prospective Neonatal Screening Study Using PCR in Saliva. CID 2017\nYamamoto et al. Contribution of Congenital CMV Infection to Permanent Hearing Loss in a Highly Seropositive Population: The Braz ilian CMV Hearing and Maternal Secondary Infection Study. CID 2020\nMussi -Pinhata et al. Seroconversion for Cytomegalovirus Infection During Pregnancy and Fetal Infection in a Highly Seropositive Population:  \"The BraCHS  Study“. JID 2018\n25%\n(n=4,000)\n75%\n(n=12,000)About 12,000 cCMV infections in the U.S. every year\nmay be attributable to primary  maternal infections*\n* Using 3,667,758 live births in US 2022 NVSS - Birth Data (cdc.gov) , stratified by maternal age group and birth order\nUnpublished estimates based on CMV seroprevalence data from NHANES; other studies 25 -50% cCMV infections attributed to primary maternal infections.cCMV infections due to \nPRIMARY infectioncCMV infections due to \nNON- PRIMARY infection\nStowell et al. Cross -sectional study of cytomegalovirus shedding and immunological markers among seropositive children and their mothers. BMC Infect Dis. 2014.\nCannon et al. Repeated measures study of weekly and daily cytomegalovirus shedding patterns in saliva and urine of healthy cy tomegalovirus -seropositive children. BMC Infect Dis. 2014.\nCannon et al. Review of cytomegalovirus shedding in bodily fluids and relevance to congenital cytomegalovirus infection. Rev Med  Virol  2011.\nSchleiss et al. Assessment of congenital cytomegalovirus prevalence among newborns in Minnesota during the COVID -19 pandemic. JAMA Network Open 2022.Children with CMV infection excrete \nlarge amounts of virus in saliva and \nurine for months\nCMV excretion peaks at 1 -2 years of age\n‒1/3 of first- time mothers will be pregnant again, \nwith a second birth within <18 months of the first\n‒More likely with day care attendance (2x)\n‒Higher risk of cCMV  in second -born childrenYoung children play a critical role in CMV transmission\n\nModeling suggest that short -duration of protection in infants can impact \ntransmission to pregnant mothers and decrease cCMV  infections\n*Protection estimated for primary infection (35% for up to 1 year)\n†Screening coverage, all CMV -seronegative vaccinated\n§Potential for increase in congenital CMV infections due to primary maternal infections predicted in high seroprevalence settings (Brazil) without booster at 15 -19yModel PopulationVaccine  \nefficacy \n(%)Duration of \nprotection\n(years)Vaccine \ncoverage \n(%)Effect 50 years \npost -vaccination\nByrne* 2m 35 1 67 85% ↓cCMV infections\nLanzieri§<1y 60 5 50 Elimination\n12-18m and 15- 19y 70 5 60 30% ↓cCMV infections \n20-29y 60 5 50 10% ↓ cCMV  infections \nAlfaro -Murillo †19-20y (CMV neg. F) 95 25 90 4% ↓ cCMV  disease\n<1y (CMV neg. F) 95 4 90 2% ↓cCMV disease\nModel PopulationVaccine  \nefficacy \n(%)Duration of \nprotection\n(years)Vaccine \ncoverage \n(%)Effect 50 years \npost -vaccination\nByrne* 2m 35 1 67 85% ↓cCMV infections\nLanzieri§<1y 60 5 50 Elimination\n12-18m and 15- 19y 70 5 60 30% ↓cCMV infections \n20-29y 60 5 50 10% ↓ cCMV  infections \nAlfaro -Murillo †19-20y (CMV neg. F) 95 25 90 4% ↓ cCMV  disease\n<1y (CMV neg. F) 95 4 90 2% ↓cCMV diseaseModels predict different impact of vaccine in US\n*Protection estimated for primary infection (35% for up to 1 year)\n†Screening coverage, all CMV -seronegative vaccinated\n§Potential for increase in congenital CMV infections due to primary maternal infections predicted in high seroprevalence settings (Brazil) without booster at 15 -19y\nThe epidemiology of CMV and cCMV is complex\nIn the United States, nearly 75% of cCMV infections due to primary maternal infection\nGlobally, most cCMV infections due to non -primary maternal infection\nAn effective CMV vaccine could reduce cCMV disease burden\nLong- lasting immunity to ensure women are protected before pregnancy  and throughout \nchildbearing years\nVaccination of toddlers could provide indirect protection  to pregnant women Summary\nACIP Members\n•Denise Jamieson (WG chair)\n•Bonnie Maldonado\nLiaisons\n•David Kimberlin (AAP)\n•Liat Greenwood Chernoff (ACNM)\n•Naima Joseph (ACOG)\n•Tabitha Hanson (AIM)\n•Leisha Nolen (CSTE)\n•Ajit Limaye (IDSA)\n•Caleb Lyu (NACCHO)\n•Maria Carrillo -Marquez (PIDS)Acknowledgments - ACIP CMV WG Members\nEx Officio Members\n•Douglas Pratt (FDA)\n•Britt Rizek  (HRSA)\n•Matthew Clark (IHS)\nConsultants\n•Andrea Ciaranello (Harvard Medical School)\n•Rana Chakraborty (University of Miami)\n•Sonja Rasmussen (Johns Hopkins University)\n•Martina Badell (SMFM)\nCDC Staff - DVD\n•Tatiana Lanzieri (WG co -lead)\n•David Sugerman (WG co -lead)\nCDC Staff - DVD\n•Tom Clark (ACIP advisor)\n•Sara Oliver (ACIP advisor) \n•Dan Filardo\n•Jessica Leung\n•Chelsea Lutz\n•Lois Park\n•Kelley Raines\n•Ashrita Rau\n•Brian WakemanAcknowledgments - ACIP CMV WG CDC Participants\nCDC Staff - non-DVD\n•Amimah  Asif (ISD)\n•Karen Pazol  (ISD)\n•Christine Olson (ISO)\n•Elizabeth Quincer  (ISO)\n•Kate Woodworth (DBDID)\n•Alison Fountain (DBDID)\n•Naomi Tepper (DRH)\nACIP Staff\n•Melinda Wharton\n•Jessica MacNeil\n•Leslie Lee\n•Stephanie Thomas\nFor more information, contact CDC 1 -800- CDC-INFO (232- 4636) TTY: 1- 888- 232- 6348 \nwww.cdc.gov \nThe findings and conclusions in this report are those of the authors and do not \nnecessarily represent the official position of the Centers for Disease Control and Prevention.", "summary": "ACIP CMV Vaccine Workgroup Cytomegalovirus (CMV) and congenital CMV (cCMV)  Epidemiology and Disease Burden Tatiana M. Lanzieri, MD, MPH ACIP CMV WG Co -Lead April 15th, 2025 Measles, Rubella and CMV Epidemiology TeamViral Vaccine Preventable Diseases BranchDivision of Viral DiseasesNational Center for Immunization & Respiratory Diseases  Review epidemiology and disease burden of CMV and cCMVObjectives More than 16,000 children born with cCMV infection in  the U.S. every year – 4.5 per 1,000…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/02-Lanzieri-cmv-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 21}
{"title": "03 paris CMV 508", "content": "© 2025 Moderna, inc. All rights reserved.\n1\nOverview of mRNA -1647:\nInvestigational CMV Vaccine\nACIP\nRobert Paris, MDApril 15, 2025\n© 2025 Moderna, inc. All rights reserved.\n2\nOutline of Presentation\n•Unmet medical need for a CMV vaccine\n•Description of Moderna’s investigational CMV vaccine \n•Overview of clinical program\n•Phase 2 safety and immunogenicity study results\n•Design of ongoing Phase 3 efficacy trial\n•Summary\n© 2025 Moderna, inc. All rights reserved.\n3\nImpact and Global Burden of Congenital CMV\nMost common \ncongenital viral infection and non- genetic \ncause of sensorineural hearing loss\n1\nMajor under -recognized \ncause of miscarriage, stillbirth, preterm birth, and infant death\n2-5\nSignificant Unmet Medical Need\nHigh Priority for Vaccine Development by WHO & NAM\n1. Boppana SB, et al. Vaccine. 2023;41:S53- S75. 2. Song X, et al. Front Pediatr . 2022;10:803568. 3. Iwasenko JM, et al. J Infect Dis. 2011; 203(11):1526- 1533. 4. Bryne J, et al. Am J Obstet  Gynecol . \n2015;213(6):905- 906. 5. Kimberlin DW, et al. 2021. Red Book: 2021– 2024 Report of the Committee on Infectious Diseases. American Academy of Pediatrics; doi:10.1542/9781610025782 -S3_037. \n6. Ssentongo P, et al. JAMA Netw Open ; 2021;4(8):e2120736. 7. CDC | CMV in Newborns. Updated January 7, 2025. https://www.cdc.gov/cytomegalovirus/congenital -infectio n/index.html. \n8. Grosse SD, et al. Perinatol . 2021;45(3):151393.\nCongenital CMV: A Major \nPublic Health Burden\nAnnual Birth Prevalence\n1 in 70 to \n1 in 208 \nbirths6\n~1 in 200 \nbirths7US Global $6-7 billion annual \nhealthcare costs in US (as of 2018)\n8\nManagement of congenital CMV challenging due to limited prevention, inconsistent screening, and lack of treatment options\n1\nEconomic & Clinical \nImpact\n© 2025 Moderna, inc. All rights reserved.\n4\n10%-15% Symptomatic at Birth\nCMV -associated death occurs during in ~5%  \nof these infants \n40%-58% develop long -term disability\nSymptoms include hearing loss, cognitive \nimpairment, developmental delay, and \nseizuresClinical Manifestations of Congenital CMV (cCMV)\nMay be present at birth & may develop or progress throughout childhood\nSource: Dollard SC, et al.  Rev Med Virol . 2007;17(5):355- 363. doi:10.1002/rmv.544  \nInfants with Congenital CMV ( cCMV )\n85%-90% Asymptomatic at Birth\n10%-15% develop long -term disability, \nmost commonly sensorineural hearing loss\n~1 in 5 infants with cCMV (symptomatic or asymptomatic at birth) \ndevelop long-term disability\n© 2025 Moderna, inc. All rights reserved.\n5CMV Vaccine Development Objective: \nPrevent CMV Infection in CMV-seronegative Women\n•Prevent CMV infection during pregnancy to reduce congenital CMV\n•Vaccinate women of child -bearing potential prior to pregnancy\nCurrent Focus\nWomen of \nChildbearing Age\nmRNA- 1647 vaccination \ninterrupts causal chain leading \nto congenital infection\nFetus Infected\n with CMVCMV infection in first \ntrimester presents highest risk of congenital disease\nPregnant \nWomen\n•Prevention of CMV infection in females, 16 -40 years of age, \nregardless of CMV serostatus \nIndication\n© 2025 Moderna, inc. All rights reserved.\n6\nModerna’s Investigational CMV Vaccine (mRNA-1647) Composed of 6 \nmRNAs Designed to Elicit Humoral and Cellular immunity to CMV Infection \nmRNA-1647 is an investigational vaccine, and the above diagram is for illustrative purposes only\nCMV, cytomegalovirus; gB, glycoprotein B.\n1. Diamond DJ, et al. Expert Rev Vaccines. 2018;17:889 -911. 2. John S, et al. Vaccine. 2018;36:1689- 1699. 3. Plotkin SA and Boppana SB. Vaccine. 2019;37:7437 -7442. \n4. Kabanova A, et al. PNAS. 2014;111:17965- 17970. 5. Scarpani  S, et al. Vaccines. 2021;9:1 -26. 6. Pass et al. N Engl J Med 2009;360: 1191- 9. 7. Bernstein, et al. Vaccine 2016; 34:313- 319.\n•5 mRNAs encode the \npentamer subunits\n•Required for CMV entry into most cell types,  including epithelial and \nendothelial cellsPentamer\n•1 mRNA encodes \nglycoprotein B \n•Mediates fusion of virus and host membranes during cell entry\n•Necessary for viral infectivity in all cell typesgB\n•Antigen selection chosen to:\n•Prevent CMV infection and subsequent fetal transmission  \n•Induce both humoral and cellular immune responses2-5 \n•43-50% efficacy for CMV infection in 2 previous trials of recombinant gB candidate vaccine1\n© 2025 Moderna, inc. All rights reserved.\n7\nCMV Vaccine (mRNA -1647) Clinical Trials in Adults\nCompleted and ongoing trials \nPopulation Study PhaseAge\n(Years)mRNA -1647 \nDose Levels \n(µg)Objectives Study Start Status\nHealthy\nAdults101 1 18-49 30-300 Safety and immunogenicity Nov 2017 Completed\n202 2 18-40 50-150Safety, immunogenicity, and \ndose selectionJan 2020 Completed\n202-\nExtension2 18-40 50-150Safety and immune persistence May 2021 Ongoing\n301 3 16-40 100Efficacy, safety, and \nimmunogenicity in femalesOct 2021 Ongoing\n© 2025 Moderna, inc. All rights reserved.\n8\nSummary: mRNA-1647 Phase 1 Trial in Adults (18-40 Years)\n•Data from Phase 1 allowed evaluation of an optimized dose range in Phase 2•Neutralizing antibody responses \n•Exploratory analysis of cell mediated immunity Immunogenicity•Generally well tolerated; no new safety concerns identified Safety•Randomized, observer blind, placebo -controlled trial \n•154 healthy participants, 18- 49 years of age (13- 19 per treatment group)\n•80 CMV -seronegative and 74 CMV -seropositive\n•Followed for 12 months after last doseDesign\n© 2025 Moderna, inc. All rights reserved.\n9\nCMV mRNA -1647 Phase 2 Dose Selection Trial in 18 -40 Year Olds\n•Primary: Safety and neutralizing antibody responses\n•Secondary: Binding antibody responsesObjectivesDesign•Randomized (3:1), observer blind, placebo -controlled trial\n•315 adult participants 18- 40 years of age (63- 109 per treatment group)\n•218 CMV -seronegative and 97 CMV -seropositive participants\n•Followed for 12 months after last dose\nDosing\n3-Dose Series \n(Month 0, 2 & 6)mRNA-1647 50 µg Placebo or\nmRNA-1647 100 µg Placebo or\nmRNA-1647 150 µg Placebo orPart 1: Dose Selection\nmRNA-1647 100 µg Placebo orPart 2: Safety Expansion\n•Focus of today’s presentation on 100 ug dose selected for further study \n© 2025 Moderna, inc. All rights reserved.\n10Solicited Local Reactions within 7 Days of injection \nCMV mRNA -1647 Phase 2 Trial in Adults\n0%20%40%60%80%100%\n1 2 3 4 5 6 7 80%20%40%60%80%100%\nDose 1Injection Site Pain Injection Site Erythema Injection Site Swelling Axillary Swelling or \nTenderness\nDose 2\nDose 3\n100 µg Placebo0%20%40%60%80%100%% Participants\nGrade 3\nGrade 2\nGrade 1\n100 µg Placebo 100 µg Placebo 100 µg Placebo\n•Pain most frequent local reaction\n•Local reactions mostly grade 1 or 2 and generally 1 -3 days duration\n© 2025 Moderna, inc. All rights reserved.\n11Solicited Systemic Reactions within 7 Days of Injection\nCMV mRNA -1647 Phase 2 Trial in Adults\n•Headache, fatigue, myalgia, and chills most common\n•Some increase in systemic reactions with 2nd & 3rd dose\n•Systemic reactions generally grade 1 or 2 of 1 -2 days duration0%20%40%60%80%100%\n1 2 3 4 5 6 7 8 9 10 11 12 13 140%20%40%60%80%100%Fever Fatigue Myalgia Headache ArthralgiaNausea / \nVomitingChills\nDose 1\nDose 2\nDose 30%20%40%60%80%100%% Participants\n100 µg Placebo 100 µg Placebo 100 µg Placebo 100 µg Placebo 100 µg Placebo 100 µg Placebo 100 µg PlaceboGrade 3 -4*\nGrade 2\nGrade 1\n*Only grade 4 reactions were fevers - 1 vaccine recipient & 1 placebo recipient after dose 1; 2 vaccine recipients after dose 2 \n© 2025 Moderna, inc. All rights reserved.\n12\nIncidence of Unsolicited Treatment Emergent Adverse Events \nWithin 28 Days After Vaccine/Placebo\nCMV mRNA -1647 Phase 2 Trial in Adults  (All Dose Levels)\nmRNA -1647 \nN=235Placebo\nN=80\nAll Related  All Related\nParticipants reporting any adverse event (AE) 87 (37.0%) 42 (17.9% )29 (36.3%) 9 (11.3% )\nSerious AEs 1 (0.4%) 0 0 0\nNon-serious AEs 86 (36.6%) 42 (17.9% ) 29 (36.3%) 9 (11.3% )\nParticipants reporting clinically relevant events\nFatal 0 0 0 0\nMedically -attended AEs 43 (18.3%) 17 (7.2% ) 17 (21.3%) 2 (2.5% )\nGrade 3 or higher (all non- serious AEs) 26 (11.1%) 6 (2.6% ) 7 (8.8%) 0\nAEs leading to discontinuation from study vaccine 7 (3.0%) 5 (2.1% ) 1 (1.3%) 0\nAEs leading to discontinuation from study 0 0 0 0\n•Related MAAEs higher in vaccine recipients; majority due to local reactions \n•No significant safety concerns identified during study \nPercentages based on  number of events / total number of participants in either the mRNA -1647 group (n=235) or in the placebo gr oup (n=80), as applicable.\n© 2025 Moderna, inc. All rights reserved.\n13\nNeutralizing Antibody Response to mRNA -1647 Based on Both \nEpithelial and Fibroblast Cell Assays\nNeutralizing \nAntibodyVaccine Antigen Biological Relevance\nEpithelial \ncellPentamer•CMV infection of epithelial, endothelial, \nmyeloid cells requires pentameric complex\nFibroblast \ncellgB•Essential for viral entry and cell fusion\n•Used to assess antibody responses to gB and \nother viral antigens \n•Pentamer- specific antibodies not effectively \nmeasured by this assay\n•Today we will present neutralizing antibody data\n•Analysis of T -cell data is ongoing\n© 2025 Moderna, inc. All rights reserved.\n14\n110100100010000100000\n0123456789101112131415161718Fibroblast Infection\nNatural Infection\n01 3 67 12 18 Month 2Neutralizing Antibody Response Demonstrated in \nCMV Seronegative  Adults\nmRNA -1647 Phase 2 Trial \n•Epithelial cell infecti on: GMTs Increased after each dose and remained above natural infection GMT through 18 months\n•Fibroblast infecti on: GMTs reached natural infection GMT at months 3 & 7, then declined at months 12 & 18mRNA -1647 100 µg Placebo\n1101001000100001000001000000\n0123456789101112131415161718GMT\n(95% CI)Epithelial Cell Infection\nNatural Infection\n01 3 67 12 18 Month 2\nGMT – geometric mean titer; Natural infection defined as GMT at baseline in CMV seropositives \n© 2025 Moderna, inc. All rights reserved.\n15\n1001000100001000001000000\n0123456789101112131415161718Epithelial Cell Infection\nNatural Infection\n01 3 67 12 18 Month 2Neutralizing Antibody Response Demonstrated  in \nCMV Seropositive  Adults\nmRNA -1647 Phase 2 Trial \n•GMTs for both assays remained above natural infection GMT through Month 18100100010000100000\n0123456789101112131415161718Fibroblast Infection\n01 3 67 12 18 Month 2mRNA -1647 100 µg Placebo\nNatural Infection\nGMT – geometric mean titer; Natural infection defined as GMT at baseline in CMV seropositives GMT\n(95% CI)\n© 2025 Moderna, inc. All rights reserved.\n16\nPhase 2 Extension Trial in Adults to Assess Persistence of Antibody\n•Primary:  Safety and neutralizing antibody -mediated immunogenicity\n•Secondary: Binding antibody -mediated immunogenicityObjectivesDesign•3-year long -term follow -up of immunogenicity and safety in participants \nwho completed the phase 2 original study\n•Provides ~4 years total follow -up after last vaccine dose \n02 6 18 24 54 36Phase 2 Main Trial\n18-Month Follow -upPhase 2 Extension Trial\nFollow -up for Additional 3 Years\n12 30 42 48Month\nVaccination\nESCMID, 2025\n© 2025 Moderna, inc. All rights reserved.\n17\nPersistence of Neutralizing Antibodies Against Epithelial Cell \nInfection  Demonstrated Through 3 Years After Vaccination\nInterim analysis of participants followed for 36 months\n•Antibody GMTs remained stable \n•nAb GMTs in CMV -seronegatives  continued to exceed natural infection GMT through 3 yearsCMV-seronegative group\n1101001000100001000001000000\n0123456789101112131415161718192021222324252627282930313233343536GMT\n(95% CI)\n013 67 12 18 Month 2 24 30 36Natural InfectionmRNA -1647 100 µg (n=24)\nPlacebo (n=22)\nESCMID, 2025; GMT –  geometric mean titer\n© 2025 Moderna, inc. All rights reserved.\n18Persistence of Neutralizing Antibodies Against Fibroblast Infection  \nDemonstrated Through 3 Years After Vaccination\nInterim analysis of participants followed for 36 months\n•Antibody GMTs remained stable through 3 yearsCMV-seronegative group\n110100100010000100000\n0123456789101112131415161718192021222324252627282930313233343536Natural Infection\nGMT\n(95% CI)\n013 67 12 18 Month 2 24 30 36mRNA -1647 100 µg (n=24)\nPlacebo (n=22)\nESCMID, 2025; GMT –  geometric mean titer\n© 2025 Moderna, inc. All rights reserved.\n19\nSummary: mRNA-1647 Phase 2 Trial in Adults (18-40 Years)\nNCT05085366•Persistence of neutralizing antibodies against epithelial cell infection \ndemonstrated through 3 years after vaccination in CMV -seronegative & \nseropositive participantsPersistence of \nAntibody•Generally well tolerated; no safety concerns identified\n•3-dose 100 µg regimen regardless of serostatusSafety\n•Highly immunogenic at 100 µg dose level \n•Neutralizing antibody GMTs against epithelial cell infection remained above natural infection GMT through 12 months after the last \nvaccination in CMV -seronegative participants\n•Boosting effect observed in CMV -seropositive participantsImmunogenicity\n© 2025 Moderna, inc. All rights reserved.\n20\nDesign of mRNA-1647 Phase 3 Pivotal Efficacy Trial\nDesign •Randomized, observer -blind, placebo -controlled study\nStudy \nPopulation•CMV -seronegative (80%) and CMV -seropositive females (20%), 16 - 40 years \nof age\n•Participants ≥ 20 years of age expected to have direct exposure in the \nhome, socially, or occupationally to at least one child ≤ 5 years of age\n•Pregnancy was exclusionary\nTreatment \nGroups •Randomized 1:1 to receive 100 µg mRNA -1647 or placebo\n•Doses at 0, 2, 6 months\nDuration of \nFollow -up•30 months \nNCT05085366\n© 2025 Moderna, inc. All rights reserved.\n21\nmRNA-1647 Phase 3 Trial: Key Objectives and Endpoints\nObjectiveCMV\nSeronegativesCMV\nSeropositives\nPrimary •Efficacy: Seroconversion from negative to \npositive serum CMV IgG starting 28 days after \n3rd injection \n•Safety: Reactogenicity, adverse events\nSecondary•Immunogenicity: Neutralizing and binding \nantibody\nAdditional•CMV Viral Shedding: Kinetics of CMV shedding in \nseronegatives who seroconverted \n•CMV Viral Shedding: Longitudinal shedding in \nurine of CMV seropositives\nNCT05085366\n© 2025 Moderna, inc. All rights reserved.\n22\nPhase 3 Pivotal Efficacy Trial in 16 –40-Year -Old Females \nis Ongoing \n•290 sites, 13 countries\n•Enrollment completed Oct 2023\n•7,484 participants enrolled\n•5,987 (80%) CMV -seronegative\n•1,497 (20%) CMV -seropositive\n© 2025 Moderna, inc. All rights reserved.\n23\nmRNA-1647 Phase 3 Efficacy Trial: Two Planned Analyses\nInterim Efficacy Analysis\n•Independent Data Safety Monitoring Board (DSMB) conducted \ncomprehensive safety and efficacy evaluation, Dec 2024\n•Notified Moderna that:\n−No safety concerns identified\n−Study should continue as planned in blinded manner \nFinal Efficacy Analysis\n•Data anticipated late 2025\nDSMB – Data Safety Monitoring Board\n© 2025 Moderna, inc. All rights reserved.\n24\nSummary: Investigational CMV Vaccine mRNA -1647 in Adults\n•Trial ongoing in seronegative and seropositive females, 16 -40 years of age Efficacy•Vaccine generally well tolerated in adults, 18 -40 years, regardless of CMV \nserostatus, in Phase 1 & 2 trials\n•No safety concerns identified from DSMB review of unblinded data in \nPhase 3 efficacy trial.Safety\nCMV Seronegatives:\n•Vaccination elicited antibody- mediated immunogenicity that exceeded \nlevels observed in natural infection\n•Immune persistence observed through 3 years after vaccination\nCMV Seropositives:\n•Vaccination boosted immune responses above baseline after first dose Immunogenicity\n© 2025 Moderna, inc. All rights reserved.\n25\n25\nTHANK YOU•Investigators\n•Study site personnel\n•Laboratory personnel\n•Most importantly, the individuals who \nparticipated in these trials", "summary": "© 2025 Moderna, inc. All rights reserved. 1 Overview of mRNA -1647: Investigational CMV Vaccine ACIP Robert Paris, MDApril 15, 2025 © 2025 Moderna, inc. All rights reserved. 2 Outline of Presentation •Unmet medical need for a CMV vaccine •Description of Moderna’s investigational CMV vaccine  •Overview of clinical program •Phase 2 safety and immunogenicity study results •Design of ongoing Phase 3 efficacy trial •Summary © 2025 Moderna, inc. All rights reserved. 3 Impact and Global Burden of…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/03-paris-CMV-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 25}
{"title": "04 lanzieri cmv 508", "content": "ACIP CMV Vaccine Workgroup\nInitial Considerations for CMV Vaccine Policy\nTatiana M. Lanzieri, MD, MPH\nACIP CMV WG Co -Lead\nApril 15th, 2025\nMeasles, Rubella and CMV Epidemiology TeamViral Vaccine Preventable Diseases BranchDivision of Viral DiseasesNational Center for Immunization & Respiratory Diseases\n\nThe burden of congenital CMV is substantial but awareness is low\nNeed to assess vaccine acceptability and feasibility of implementation\nPrimary maternal infections have a higher risk of vertical transmission, are \nestimated to cause most cCMV infections in the U.S., and result in more severe \ncCMV disease if occurring in the first trimester of pregnancy\nVaccination before pregnancy, and long -lasting protection throughout childbearing years \nwould be needed\nCMV seroprevalence increases with age, but certain groups of the population already have \nhigh seroprevalence by adolescenceCMV as a public health problem\nCMV gBand pentamer complex ( gH, gL, UL128, UL130, UL131)\n-3 doses: 0, 2, 6 months after the first dose\nPhase 3 trial (ongoing)\n-Randomization: 1:1 vaccine:placebo ,\nwithin each serostatus group, and\nstratified by age group\n-Follow -up: 24 months after the 3rddose,\nwith an extension to 48 months for a \nsubset of the cohortModerna mRNA -1647 CMV vaccine\nStudy Details | A Study to Evaluate the Efficacy, Safety, and Immunogenicity of mRNA -1647 Cytomegalovirus (CMV) Vaccine in Healt hy Participants 16 to 40 Years of Age | \nClinicalTrials.gov7,500 non -pregnant \nfemales \n(16-40 years)\n5,500\nCMV IgG seronegative\n(Vaccine efficacy)2,000 \nCMV IgG seropositive\n(Safety and reactogenicity)\n–Vaccine efficacy against primary infection in CMV -seronegative (vaccine vs. placebo recipients) \nfrom 28 days up to 24 -48 months after the 3rd dose\n›Primary infection: seroconversion from negative to positive for IgG against CMV antigens \nnot included in vaccine\n–Safety and reactogenicity in all participants\n–Immunogenicity  at day 1 and months 3, 7, 12\n–Immune persistence at months 18, 24, and 30 \n›gB and pentamer  antigen -specific neutralizing antibody titers and binding antibody \nconcentrations in CMV -seronegative vaccine vs. placebo recipients\n–\n–Symptomatic primary infection, urinary CMV excretion (CMV -seropositive)\n–Moderna mRNA -1647 CMV vaccine – clinical trial endpoints\nStudy Details | A Study to Evaluate the Efficacy, Safety, and Immunogenicity of mRNA -1647 Cytomegalovirus (CMV) Vaccine in Healt hy Participants 16 to 40 Years of Age | ClinicalTrials.govSecondaryPrimary\nExploratory\nNo safety concerns\nImmunogenicity – need to better understand differences in neutralizing \nantibody levels against epithelial cell and fibroblast entry; antibody -dependent \ncellular cytotoxicity and phagocytosis (ADCC & ADPC)\nLong -term protection –  some data showing antibody persistence through at \nleast 3 years following dose 1WG interpretation of data from Moderna’s mRNA -1647 \nvaccine phase 1 and phase 2 trials\nModerna’s planned vaccine indication is for non- pregnant  females 16 -40 years; 3- dose series \n(6 months) \nEfficacy will be assessed only for primary infection among initially CMV -seronegative subjects\nData on duration of immunity will be limited; need to ensure protection before pregnancy and \nthroughout childbearing age years\nEfficacy against vertical transmission, cCMV  infection or disease?\nBetter understanding of correlates of protection against vertical transmission is needed\nBenefit to CMV -seropositive individuals yet unknown while serological testing prior to \nvaccination would pose implementation challenges\nGroups considered for vaccine recommendations might change as data from future clinical trials (e.g. adolescents, transplant patients) become availableWG considerations on Moderna’s mRNA -1647 vaccine \nphase 3 trial\nNext steps\nPublic \nHealth \nProblemBenefits \nand \nHarmsValues FeasibilityResource \nUseEquity AcceptabilityEvidence to Recommendation ( EtR) Domains\nAn effective CMV vaccine could reduce cCMV disease burden\nOver 16,000 children born with cCMV infection in the U.S. every year; nearly 3,000 with cCMV disease\nmRNA -1647 CMV vaccine candidate\nShown to be safe and immunogenic in phase 1 and 2 studies\nEfficacy data on prevention of primary CMV infection in CMV -seronegative women 16 -40 years of age from \nongoing phase 3 trial expected next year\nNeed to ensure protection against CMV infection before pregnancy to reduce vertical transmission\nLow awareness and potential need for serological screening might pose implementation \nchallenges\nThe CMV ACIP WG will meet regularly to review data and develop CMV vaccine policy \noptions Conclusions\nACIP Members\n•Denise Jamieson (WG chair)\n•Bonnie Maldonado\nLiaisons\n•David Kimberlin (AAP)\n•Liat Greenwood Chernoff (ACNM)\n•Naima Joseph (ACOG)\n•Tabitha Hanson (AIM)\n•Leisha Nolen (CSTE)\n•Ajit Limaye (IDSA)\n•Caleb Lyu (NACCHO)\n•Maria Carrillo -Marquez (PIDS)Acknowledgments - ACIP CMV WG Members\nEx Officio Members\n•Douglas Pratt (FDA)\n•Britt Rizek  (HRSA)\n•Matthew Clark (IHS)\nConsultants\n•Andrea Ciaranello (Harvard Medical School)\n•Rana Chakraborty (University of Miami)\n•Sonja Rasmussen (Johns Hopkins University)\n•Martina Badell (SMFM)\nCDC Staff - DVD\n•Tatiana Lanzieri (WG co -lead)\n•David Sugerman (WG co -lead)\nCDC Staff - DVD\n•Tom Clark (ACIP advisor)\n•Sara Oliver (ACIP advisor) \n•Dan Filardo\n•Jessica Leung\n•Chelsea Lutz\n•Lois Park\n•Kelley Raines\n•Ashrita Rau\n•Brian WakemanAcknowledgments - ACIP CMV WG CDC Participants\nCDC Staff - non-DVD\n•Amimah  Asif (ISD)\n•Karen Pazol  (ISD)\n•Christine Olson (ISO)\n•Elizabeth Quincer  (ISO)\n•Kate Woodworth (DBDID)\n•Alison Fountain (DBDID)\n•Naomi Tepper (DRH)\nACIP Staff\n•Melinda Wharton\n•Jessica MacNeil\n•Leslie Lee\n•Stephanie Thomas\nFor more information, contact CDC 1 -800- CDC-INFO (232- 4636) TTY: 1- 888- 232- 6348 \nwww.cdc.gov \nThe findings and conclusions in this report are those of the authors and do not \nnecessarily represent the official position of the Centers for Disease Control and Prevention.", "summary": "ACIP CMV Vaccine Workgroup Initial Considerations for CMV Vaccine Policy Tatiana M. Lanzieri, MD, MPH ACIP CMV WG Co -Lead April 15th, 2025 Measles, Rubella and CMV Epidemiology TeamViral Vaccine Preventable Diseases BranchDivision of Viral DiseasesNational Center for Immunization & Respiratory Diseases  The burden of congenital CMV is substantial but awareness is low Need to assess vaccine acceptability and feasibility of implementation Primary maternal infections have a higher risk of…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/04-lanzieri-cmv-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 11}
{"title": "01 Sugerman measles 508", "content": "U.S. Measles Update\nApril 15, 2025Centers for Disease Control and Prevention\nNational Center for Immunization & Respiratory Diseases\nCAPT David Sugerman, MD MPH FACEP, USPHS\nSenior Scientist, 2025 Measles Response\nDivision of Viral Diseases / National Center for Immunization and Respiratory Diseases\nUS Centers for Disease Control and Prevention (CDC)\nHistory of measles cases in the U.S., 1962 –2023\n†Measles was declared eliminated in the U.S. in 2000 by WHO/PAHO. Elimination is defined as the absence of endemic measles \ntransmission in a region for ≥ 12 months in the presence of a well -performing surveillance system\nTexas: \n2025: 541 cases*\nMMR % unknown Measles outbreaks with 50+ cases and MMR vaccine coverage among affected populations – U.S. 2001 –2025\n*As of April 11th, 2025\n \nNational and State Level 2 -dose MMR Coverage among \nKindergartners: 2023 –2024 \nhttps://www.cdc.gov/mmwr/volumes/73/wr/mm7341a3.htm\nMMR (2 doses)\n2019 -20 95.2%\n2020 -21 93.9%\n2021 -22 93.0%\n2022 -23 93.1%\n2023 -24 92.7%\nCounty -level coverage with ≥ 1 dose of MMR vaccine \nSeeskin , ZH et al.  Estimating county -level vaccination coverage using small area estimation with the National \nImmunization Survey -Child, Vaccine, Vol 42, Issue 3,2024, Pages 418 -425.\n\nU.S. monthly measles cases by rash onset, 2023 –2025\nYearConfirmed measles \ncases\n2023 59\n2024 285\n2025 712*\n*As of April 10th, 2025.050100150200250300350400\nJan Feb Mar Apr May Jun JulAug Sep Oct Nov Dec Jan Feb Mar Apr May Jun JulAug Sep Oct Nov Dec Jan Feb Mar Apr\n2023 2024 2025\nU.S. measles outbreaks, 2023 –2025 \nYear No. outbreaksNo. (%) cases \nassociated\nwith outbreaks / total \ncases Outbreak size,\nmedian cases \n(maximum)Outbreak duration,\nmedian days \n(maximum)\n2023 4 28/58 (48%) 7 (10) 22 (31)\n2024 16 194/285 (68%) 4 (58) 17.5 (131)\n2025 7 660/712 (93%) 5 (591)12.5 (5 outbreaks \nongoing)\n•As of April 10 , 2025, Texas, New Mexico, and Oklahoma have reported 591 confirmed cases associated with this \nsingle outbreak (528 in Texas ,56 in New Mexico , and 7 in Oklahoma ).\nAs of April 10, 712 confirmed measles cases have been \nreported by 25 states in 2025\n\nNational and Southwest Outbreak Measles Cases, 2025  \n(As of April 10th, 2025)*\n\n•Age\n-Under 5 years: 225 (32%)\n-5-19 years: 274 (38%)\n-20+ years: 198 (28%)\n-Age unknown: 15 (2%)\n•Vaccination Status: \n-Unvaccinated or Unknown: 97%\n-One MMR dose: 1%\n-Two MMR doses: 2%\n•Hospitalizations\n-11% of cases (79 of 712) for management of measles \ncomplications\n•Deaths - 2 in Texas and 1 in New Mexico  Epidemiology of U.S. measles cases in 2025 (n=712)\n\nDistribution of Distinct Sequence Identifiers ( DSIds ) for measles \ngenotypes B3 and D8 detected in the U.S. by epidemiological week \nin 2025\nD8-9171\n0510152025303540\n1 2 3 4 5 6 7 8 9 10 11 12# Genotyped Cases\nEpidemiological Week\nB3-9260 B3-8777 B3-9259 B3-8841 B3-8661 D8-9171\nD8-9274 D8-9304 D8-9322 D8-9323 D8-5963Green: B3\nBlue:    D8\n•Texas Epi -Aid: 15 deployers from CDC provided on -site technical  assistance  in Texas \nduring 3/4 -4/1, with another team deploying this week.  \n-Provided infection prevention control support for 7 healthcare facilities with ventilation \nassessments by NIOSH\n-Review ed school infection control activities and risk mitigation strategies \n-Developed an int ernal dashboard for TX to track cases by location and exposure location\n•Provide remote technical assistance to multiple state health departments\n•Biweekly national measles calls with public health partners \n•Biweekly trilateral calls with Canada and Mexico to share updates and lessons learned\n•Continue to make additional, outbreak -related MMR vaccine doses available for \nhealth departments to order at their requestCDC 2025 measles outbreak response efforts\n•Provider Outreach \n-Health Alert Network (HAN) released - Expanding Measles Outbreak in Texas and New \nMexico and Guidance for the Upcoming Travel Season\n-Clinician Outreach and Communication Activity (COCA) and Epi -X alerts \n-Shared a provider letter summarizing routine and outbreak -related MMR vaccination \nrecommendations  \n•Laboratory Support \n-Coordination with the APHL Vaccine Preventable Disease Reference Centers (VPD -RCs) for  \ngenotyping and  sequencing\n-Expanded and standardized testing for wastewater surveillance for measles with the \nNational Wastewater Surveillance System (NWSS) and Center of Excellence in Texas.\n•Ongoing modeling work to determine risk CDC 2025 measles outbreak response efforts (continued)\nFor more information, contact CDC/ATSDR\n1-800-CDC-INFO (232 -4636)\nTTY:  1 -888-232-6348    www.cdc.gov           www.atsdr.cdc.gov \nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position \nof the Centers for Disease Control and Prevention and the Agency for Toxic Substances and Disease Registry.\nThank you", "summary": "U.S. Measles Update April 15, 2025Centers for Disease Control and Prevention National Center for Immunization & Respiratory Diseases CAPT David Sugerman, MD MPH FACEP, USPHS Senior Scientist, 2025 Measles Response Division of Viral Diseases / National Center for Immunization and Respiratory Diseases US Centers for Disease Control and Prevention (CDC) History of measles cases in the U.S., 1962 –2023 †Measles was declared eliminated in the U.S. in 2000 by WHO/PAHO. Elimination is defined as the…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/01-Sugerman-measles-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 14}
{"title": "01 Loehr mening 508", "content": "Introduction to Meningococcal Vaccines \nSession\nJamie Loehr, MD\nAdvisory Committee on Immunization Practices\nApril 16, 2025National Center for Immunization & Respiratory Diseases\n1\n3 Terms of Reference\nGSK Pentavalent (MenABCWY) Vaccine\nMenQuadfi Use in Infants\nAdolescent Schedule Change\n2 of 8\n3 Terms of Reference\nGSK Pentavalent (MenABCWY) Vaccine\n–Licensure:  February 14, 2025\n–ACIP Vote:  April 16, 2025 (today)\nMenQuadfi Use in Infants\n–Licensure:  May 2025 (anticipated)\n–ACIP Vote:  June 2025 (anticipated)\nAdolescent Schedule Change\n–WG deliberations ongoing\n3 of 8\nToday\nGSK Pentavalent (MenABCWY) Vaccine:  Update of EtR and \nWork Group Considerations\nUpdates to Meningococcal Vaccines VFC Resolution\nIntroduction to MenQuadfi Label Change for Infants\nMenQuadfi in Infants:  Safety and Immunogenicity\nWork Group Considerations Regarding MenQuadfi in Infants\n4 of 8\nToday\nGSK Pentavalent (MenABCWY) Vaccine:  Update of EtR and \nWork Group Considerations\nUpdates to Meningococcal Vaccines VFC Resolution\n–VOTE (including VFC Vote)\nIntroduction to MenQuadfi Label Change for Infants\nMenQuadfi in Infants:  Safety and Immunogenicity\nWork Group Considerations Regarding MenQuadfi in Infants\n5 of 8\nGSK Pentavalent Vaccine\nAfter immunogenicity data presented to ACIP , Bexsero \n(comparator) label changed from 0, ≥1 month to 0, 6 months \nLonger intervals between vaccine doses associated with higher immunogenicity\n–As a result, pentavalent now has comparatively lower \nimmunogenicity than MenB\nSome data points in label have also been updated\nWG members voiced need for ACIP to review updated data in \nconsideration of vote, although WG recommendation has not changed\n6 of 8\nACIP Meningococcal Vaccines Work Group \nACIP Members on the WG\n Jamie Loehr (Chair)\n Charlotte Moser\nEx Officio WG Members\n Margaret Bash (FDA)\n Xin-Xing Gu (NIH)\n7 of 8WG Liaisons and Consultants\n Amra Resic (AAFP)\n Mary Healy (AAP) \n Barb Fluty (ACHA)\n Karyn Lyons (AIM)\n Stephanie Schauer (AIM)\n Paul Cieslak (CSTE)\n Kathy Hsu (IDSA)\n Joseline Zafack (NACI)\n Jeff Goad (NFID)\n Jessica Cataldi (PIDS)\n Amy Middleman (SAHM)\n Kathy Poehling (Wake Forest)\n Lynn Bahta (Minnesota Department of Health)\n David Stephens (Emory)\nAcknowledgements \nCDC Contributors\n Sarah Schillie (DBD/NCIRD) – Meningococcal Lead\n Jennifer Collins (DBD/NCIRD) – Hib Lead\n Lucy McNamara (DBD/NCIRD)\n Avnika Amin (DBD/NCIRD)\n LeAnne Fox (DBD/NCIRD)\n Susan Hariri (DBD/NCIRD)\n Amy Rubis (DBD/NCIRD)\n Jenny Thomas (DBD/NCIRD)\n Noele Nelson (DBD/NCIRD)\n Alison Albert (DBD/NCIRD)\n Shelby Miller (DBD/NCIRD)\n Michael Williams (DBD/NCIRD)\n Michelle Hughes (DBD/NCIRD)\n Madhura Vachon (DBD/NCIRD)\n Gabrielle Cooper (DBD/NCIRD)\n Xiaoyu Dong (ISD/NCIRD)\n Andrew Leidner (ISD/NCIRD)\n Katherine Lean (DBD/NCIRD)\n Ismael Ortega- Sanchez (CORVD/NCIRD)\n Jonathan Duffy (DHQP/NCEZID)\n Pedro Moro (DHQP/NCEZID)\n Tanya Myers (DHQP/NCEZID) \n Madeleine Valier (ISD/NCIRD)\n Sam Graitcer (ISD/NCIRD)\n Leslie Lee (OD/NCIRD)\n Manisha (Mo) Patel (OD/NCIRD)\n Jessica MacNeil (ACIP Secretariat)\n Hannah Rosenblum (ACIP Secretariat)\n Melinda Wharton (ACIP Secretariat)\n8 of 8", "summary": "Introduction to Meningococcal Vaccines  Session Jamie Loehr, MD Advisory Committee on Immunization Practices April 16, 2025National Center for Immunization & Respiratory Diseases 1 3 Terms of Reference GSK Pentavalent (MenABCWY) Vaccine MenQuadfi Use in Infants Adolescent Schedule Change 2 of 8 3 Terms of Reference GSK Pentavalent (MenABCWY) Vaccine –Licensure:  February 14, 2025 –ACIP Vote:  April 16, 2025 (today) MenQuadfi Use in Infants –Licensure:  May 2025 (anticipated) –ACIP Vote: …", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/01-Loehr-mening-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 8}
{"title": "02 Schillie mening 508", "content": "GSK Pentavalent ( MenABCWY ) Vaccine:  \nReview of Updated EtR and Work Group \nConsiderations\nSarah Schillie, MD, MPH, MBA\nAdvisory Committee on Immunization Practices\nApril 16, 2025National Center for Immunization & Respiratory Diseases\n1\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position o f \nthe U. S. Centers for Disease Control and Prevention.\nMeningococcal Vaccine Recommendations \n2 of 56One MenACWY  dose at \nage 11 –12 years and a \nbooster dose at age 16 \nyears (routine)\nTwo MenB  doses at age \n16–23 years (shared \nclinical decision -making \n[SCDM])\n–Preferred age range: 16–18 years \n\nRisk-Based Meningococcal Vaccine Recommendations \n2MenACWY  (≥2 months) MenB  (≥10 years)\nAsplenia (functional or anatomic) √ √\nComplement deficiency/ \ncomplement inhibitor use√ √\nHIV infection √\nSome microbiologists √ √\nExposure during outbreak √ √\nTravel to hyperendemic areas √\nFirst -year college students (if not \npreviously vaccinated at ≥16 years) √\nInterchangeability of Vaccine Products\nMenACWY\n–Brands are interchangeable\n–Same brand is preferred, but not required, for all doses in a series\nMenB\n–Brands are not interchangeable\n–Same brand must be used for all doses in a series (including booster \ndoses)\n4 of 56\nTwo Pentavalent MenABCWY  Vaccines\nPfizer (Penbraya) GSK ( Penmenvy )\nACWY component Nimenrix (not licensed in U.S.) Menveo\nB component Trumenba Bexsero\nSchedule 2 doses, 6 months apart 2 doses, 6 months apart\nAge 10–25 years 10–25 years\nLicensed October 20, 2023 February 14, 2025\nACIP Vote October 25, 2023 Today\n5 of 56\nPfizer Pentavalent Vaccine\n6 of 56May be used when both MenACWY  and MenB  \nare indicated at the same visit for: \n 1) Healthy persons aged 16 –23 years \n(routine schedule) when shared clinical decision-\nmaking favors administration of MenB  vaccine \nand \n 2) Persons aged ≥10 years who are at \nincreased risk for meningococcal disease (e.g., \nbecause of persistent complement deficiencies, complement inhibitor use, or functional or anatomic asplenia) \n\nConsiderations\nEach pentavalent vaccine assessed separately by Work Group\n—Lack of data directly comparing the two vaccines\nThe MenACWY  and MenB vaccine indications have not \nchanged with the availability of pentavalent vaccine\nACIP previously voiced preference to harmonize \nrecommendations between the Pfizer and GSK pentavalent vaccines\n–Unless a vaccine -specific reason to have a different \nrecommendation exists 7 of 56\nAssessing Immunogenicity\nExogenous complement (“traditional” hSBA assays)\nSeroprotection\nSeroresponse *  \nGMTs\nEndogenous complement \nImmunologic Vaccine Effectiveness:  Immune response against diverse \nserogroup B strains\nSerologic correlate of protection exists only for serogroup C\n*E.g.:  a post- vaccination hSBA  titer at least 4 -fold the LOD or ≥LLOQ, whichever is greater, for participants with pre -vaccination hSBA  titer \n<LOD, a post -vaccination hSBA  titer at least 4 -fold the LLOQ for participants with pre -vaccination hSBA  titer ≥LOD and <LLOQ, and a post -\nvaccination hSBA  titer at least 4 -fold the pre -vaccination hSBA  titer for participants with pre -vaccination hSBA  titer ≥ LLOQ\nLOD, limit of detection; LLOQ, lower limit of quantitation \nPICO Questions:  GSK Pentavalent Vaccine\nPICO 1:\nShould the GSK pentavalent vaccine be included as an option for MenACWY /MenB  \nvaccination in people currently recommended to receive both vaccines at the same \nvisit?\n– For example, 16 year- olds*\nPICO 2:\nShould the GSK pentavalent vaccine be included as an option for people currently recommended to receive MenACWY  only?\n–For example, 11 –12 year -olds\nPICO 3:\nShould the GSK pentavalent vaccine be included as an option for people currently recommended to receive MenB  only?\n– For example, during a serogroup B outbreak\n*16 year -olds who decide to receive MenB  vaccine based on shared clinical decision -making9 of 56\nAcronyms\nQ=Quadrivalent ( MenACWY  vaccine)\nB=MenB  vaccine\nP=Pentavalent ( MenABCWY  vaccine)\n10 of 56\nAcronyms\nCurrent Recommendation:  Q-QB-B or Q -Q\nPICO 1:\n Should the GSK pentavalent vaccine be included as an option for MenACWY /MenB  vaccination in \npeople currently recommended to receive both vaccines at the same visit?  Q -P-B\nPICO 2:\n Should the GSK pentavalent vaccine be included as an option for people currently recommended to \nreceive MenACWY  only?  P-P\nPICO 3:\n Should the GSK pentavalent vaccine be included as an option for people currently recommended to receive MenB  only?  Q-P-PQ=Quadrivalent ( MenACWY  vaccine)\nB=MenB  vaccine\nP=Pentavalent ( MenABCWY  vaccine)\n11 of 56\nAcronyms\nCurrent Recommendation:  Q-QB-B or Q -Q\nPICO 1:  “Yes” for Pfizer pentavalent vaccine\n Should the GSK pentavalent vaccine be included as an option for MenACWY /MenB  vaccination in \npeople currently recommended to receive both vaccines at the same visit?  Q -P-B\nPICO 2:  “No” for Pfizer pentavalent vaccine\n Should the GSK pentavalent vaccine be included as an option for people currently recommended to \nreceive MenACWY  only?  P-P\nPICO 3:  “No” for Pfizer pentavalent vaccine\n Should the GSK pentavalent vaccine be included as an option for people currently recommended to receive MenB  only?  Q-P-PQ=Quadrivalent ( MenACWY  vaccine)\nB=MenB  vaccine\nP=Pentavalent ( MenABCWY  vaccine)\n12 of 56\nUpdated Evidence-to-Recommendations \nFramework:  GSK Pentavalent Vaccine\nEtR Domain QuestionWork Group \nDetermination – \nPICO 1Work Group \nDetermination – \nPICO 2Work Group \nDetermination – \nPICO 3\nPublic health \nproblemIs invasive meningococcal disease a problem of public health importance?Yes Yes Yes\nBenefits and harmsHow substantial are the desirable anticipated effects? Small Small Small\nHow substantial are the undesirable anticipated effects? Minimal Small Minimal\nDo the desirable anticipated effects outweigh the undesirable effects?Favors \nintervention/ \nfavors comparisonFavors intervention/ \ncomparison/bothFavors \nintervention/ \ncomparison/both\nWhat is the overall certainty of evidence? Low Low Low\nValues Does the target population feel the desirable effects are large relative to the undesirable effects?Yes Probably yes Probably yes/yes/\ndon’t know\nIs there important variability in how patients value the \noutcome?Probably not/no Probably/probably \nnotProbably/probably \nnot\nAcceptability Is the intervention acceptable to key stakeholders? Yes Probably yes Probably yes/yes\nResource use Is the intervention a reasonable and efficient allocation of \nresources?Yes Probably no/varies Varies\nHealth equity What would be the impact of the intervention on health equity?Probably \nincreasedProbably \nincreased/increasedProbably increased\nFeasibility Is the intervention feasible to implement? Yes Probably yes/yes Yes\nPublic health problem\n0.000.200.400.600.801.001.201.40\n1996 2000 2005 2010 2015 2020 2024Incidence per 100,000\nYearMeningococcal Disease Incidence –\nUnited States, 1996 –2024*\nAbbreviations: MenACWY vaccine = quadrivalent (serogroups A, C, W, and Y) meningococcal conjugate vaccine; MenB  vaccine = serogroup B meningococcal vaccine\nSource: 1996– 2024 NNDSS Data. *2024 NNDSS data are preliminary.0.15 cases/100,000 populationMenACWY vaccine1.2 cases/100,000 \npopulation\nMenB  vaccine\nPublic Health Problem\nIs invasive meningococcal disease a problem of public health importance?\nNo Probably \nnoProbably \nyesYes VariesDon’t \nknow\nPICO 1 (QPB vs. QQBB):\nMenABCWY vs. MenACWY + MenBX\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY vs. MenACWYX\nPICO 3 (QPP vs. QQBB):  \nMenABCWY vs. MenB  X\nPICO 1 (QPB vs. QQBB):\nMenABCWY vs. MenACWY + MenBX\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY vs. MenACWYX\nPICO 3 (QPP vs. QQBB):  \nMenABCWY vs. MenB  X\n17 of 56\nBenefits and harms\nSerogroup B Immunogenicity Lower than \nPreviously Shared with ACIP\nComparator of Bexsero at 0, 2 month interval\n–August 2024:  Bexsero label changed from 0, ≥1 month to  \n0, 6 months \nLonger intervals between vaccine doses associated with \nhigher immunogenicity\nAdditionally, some data points in label have been updated\n19 of 56\nWork Group Assessment\nClinical significance of comparatively lower \nimmunogenicity uncertain\n–Serologic correlate of protection lacking for serogroup B disease\nThe Work Group’s recommendation for the GSK pentavalent vaccine remains unchanged\n–ACIP to weigh the change in immunogenicity in their deliberations \n20 of 56\nPrevious Synthesis to ACIP \n(Remains Unchanged from June 2024):\nFor “traditional” exogenous hSBA  titers against 4 vaccine indicator strains, \nMenABCWY  was:\n–Non -inferior to MenB  0, 2 months for 3 strains \n–Non -inferior to MenB  0, 6 months for 2 strains\nEndogenous complement hSBA  assay against a broad range of strains \n(Immunologic Vaccine Effectiveness):  Success criteria met\n–Although MenABCWY  had lower point estimates (especially compared to MenB  0,6)\n21 of 56\nPrevious Synthesis Unchanged Regarding:\nACWY Immunogenicity  and Safety\nMenABCWY  non- inferior to MenACWY  in most study groups\n–Except serogroup A for 1 dose MenABCWY  vs. 1 dose MenACWY  in \nnaïve recipients\n•Serogroup A disease very rare in the United States\nMenABCWY  safety profile similar to MenB , except slightly more unsolicited \nadverse events with MenABCWY\n–More adverse events than with MenACWY\n22 of 56\n23 of 56\nPresentation to \nACIP , Jun 2024Package Insert,Feb 2025•Poorer immunogenicity when comparing to 0,6 month schedule\n•Success criterion not met for all strains (unchanged since June ACIP)\n•Some change in numbersComposite response= hSBA  \n≥LLOQ for all 4 indicator strains\n24 of 56\nPresentation to \nACIP , Jun 2024Package Insert,Feb 2025•Poorer immunogenicity when comparing to 0,6 month schedule\n•Success criterion not met for all strains (unchanged since June ACIP)\n•Some change in numbers\nPorA\nNon-inferiority not demonstrated for PorA  strain for 0, 2 or 0, 6 \nmonth comparison\n–PorA  indicator strain is important because it represents the outer \nmembrane vesicle (OMV) component of the vaccine and has bearing on \ncross -protection\n25 of 56\nPenmenvy (GSK) \nPackage Insert Composite response= hSBA  \n≥LLOQ for all 4 indicator strains\nPenmenvy (GSK) \nPackage Insert\nPenbraya  (Pfizer) \nPackage InsertComposite response= hSBA  \n≥LLOQ for all 4 indicator strains\n2\nPresentation to \nACIP , Jun 2024\nPackage Insert,Feb 2025•Poorer immunogenicity when comparing to 0,6 month schedule\n•Success criterion met\n•Minimal change in numbers\n28 of 56\n8GSK presentation \nto ACIP , Jun 2024\nIntegrated FDA Review, Mar 2025•Poorer immunogenicity when comparing to 0,6 month schedule\n•Success criterion met\n•No change in numbers \n\nReverse Cumulative Distribution of hSBA  \nAgainst Indicator Strains\n28\npentavalent\n30 of 56\nReverse Cumulative Distribution of hSBA  \nAgainst Indicator Strains\n28\npentavalentMenB\n31 of 56\nEnc-hSBA  against 110 Isolates by Clonal \nComplex\nFor PorA /OMV:  enc -hSBA  \nlikely most reflective of U.S. \nstrains and exogenous assay \nlikely most reflective of New Zealand strain\nCC 41/44 represents 72/179 \n(40.2%) of U.S. isolates from \n2020 -2024\n•For serogroups CWY , 1 dose \npentavalent immunogenicity \ngreater than 1 dose Menveo \nfor naïve recipients\n•For serogroup A, 1 dose \npentavalent immunogenicity \nlower than 1 dose Menveo for \nnaïve recipients (Serogroup A \ndoes not circulate in U.S.)\n•For primed recipients, 1 -dose \nimmunogenicity similar for serogroups A, C, W, and Y\nSerious Adverse Events Assessed as Possibly Related to Vaccination\n34 of 56StudyNumber\nPentavalent MenACWY MenB MenACWY/MenB\nSaez -Llorens 201510 0 -- --\nBlock 2015 0 0 0 --\nWelsch 2018 0 0 -- --\nVesikari 20212 \n(seizure, connective \ntissue disorder)-- 0 --\nBeran 2021 0 01 \n(syncope)0\nv72_722 1 \n(neuromyelitis optica)1\n(pyrexia)1\n(ulcerative colitis)--\nMenABCWY_019 0 0 -- --\n1One related event during extension study in a recipient of a MenABCWY that contained ¼ of the usual OMV component\n2These were reported as related to vaccination by investigators; however, they were not considered adverse drug reactions rela ted to vaccination after GSK and independent evaluation\nSerogroup B Immunogenicity Summary\nMenABCWY  immunogenicity slightly lower than MenB\n–Clinical significance uncertain as serologic correlate of protection is lacking\nFor “traditional” exogenous hSBA  titers against 4 vaccine indicator strains, \nMenABCWY  was:\n–Non -inferior to MenB  0, 2 months for 3 strains \n–Non -inferior to MenB  0, 6 months for 2 strains\nEndogenous complement hSBA  assay against a broad range of strains \n(Immunologic Vaccine Effectiveness):  Success criteria met\nWork Group’s interpretation has not changed\nACIP to consider the magnitude of the difference in immunogenicity in their \ndeliberations35 of 56\nHow substantial are the desirable  anticipated effects?Benefits and Harms\nMinimal Small Moderate Large VariesDon’t \nknow\nPICO 1 (QPB vs. QQBB):\nMenABCWY  vs. MenACWY  + MenBX\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY  vs. MenACWYX X X\nPICO 3 (QPP vs. QQBB):  \nMenABCWY  vs. MenB   X\nPICO 1 (QPB vs. QQBB):\nMenABCWY  vs. MenACWY  + MenBX\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY  vs. MenACWYX\nPICO 3 (QPP vs. QQBB):  \nMenABCWY  vs. MenB   X\n36 of 56\nHow substantial are the undesirable  anticipated effects?Benefits and Harms\nMinimal Small Moderate Large VariesDon’t \nknow\nPICO 1 (QPB vs. QQBB):\nMenABCWY  vs. MenACWY  + MenBX\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY  vs. MenACWYX X\nPICO 3 (QPP vs. QQBB):  \nMenABCWY  vs. MenB   X X\nPICO 1 (QPB vs. QQBB):\nMenABCWY  vs. MenACWY  + MenBX\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY  vs. MenACWYX\nPICO 3 (QPP vs. QQBB):  \nMenABCWY  vs. MenB   X\n37 of 56\nDo the desirable effects outweigh the undesirable effects?Benefits and Harms\nFavors \ninterventionFavors \ncomparisonFavors \nbothFavors \nneitherVariesDon’t \nknow\nPICO 1 (QPB vs. QQBB):\nMenABCWY  vs. MenACWY  + MenBX\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY  vs. MenACWYX X X\nPICO 3 (QPP vs. QQBB):  \nMenABCWY  vs. MenB   X X\nPICO 1 (QPB vs. QQBB):\nMenABCWY  vs. MenACWY  + MenBX X*\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY  vs. MenACWYX X X\nPICO 3 (QPP vs. QQBB):  \nMenABCWY  vs. MenB   X X X\n38 of 56*Represents minority opinion added since last presented to ACIP\nWhat is the overall certainty of this evidence for the critical outcomes?Benefits and Harms:  Short -term Immunity\nNo studies \nfoundVery low Low Moderate High\nPICO 1 (QPB vs. QQBB):\nMenABCWY  vs. MenACWY  + MenBX X\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY  vs. MenACWYX X\nPICO 3 (QPP vs. QQBB):  \nMenABCWY  vs. MenB   X X\nPICO 1 (QPB vs. QQBB):\nMenABCWY  vs. MenACWY  + MenBX X\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY  vs. MenACWYX X\nPICO 3 (QPP vs. QQBB):  \nMenABCWY  vs. MenB   X X\n39 of 56\nWhat is the overall certainty of this evidence for the critical outcomes?Benefits and Harms:  Serious Adverse Events\nNo studies \nfoundVery low Low Moderate High\nPICO 1 (QPB vs. QQBB):\nMenABCWY  vs. MenACWY  + MenBX X\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY  vs. MenACWYX X\nPICO 3 (QPP vs. QQBB):  \nMenABCWY  vs. MenB   X X\nPICO 1 (QPB vs. QQBB):\nMenABCWY  vs. MenACWY  + MenBX X\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY  vs. MenACWYX X\nPICO 3 (QPP vs. QQBB):  \nMenABCWY  vs. MenB   X X\n40 of 56\nResource use\nPediatric Price Per Dose\nPublic Private \nMenACWYMenveo $119.986* $166.747\nMenQuadfi $114.36* $171.972\nMenBTrumenba $142.73* $207.32*\nBexsero $154.504* $237.126\nMenABCWYPenbraya $189.35 $230.75\nPenmenvy *$181.00* (final price:  \npending negotiation)$241.00** (final \nprice:  $230- 255)\n42 of 56https://www.cdc.gov/vaccines -for-children/php/awardees/current -cdc-vaccine -price -list.html*Updated contract price **Value used in CDC cost- effectiveness model \nPediatric Price Per Dose\nPublic Private \nMenACWYMenveo $119.986* $166.747\nMenQuadfi $114.36* $171.972\nMenBTrumenba $142.73* $207.32*\nBexsero $154.504* $237.126\nMenABCWYPenbraya $189.35 $230.75\nPenmenvy *$181.00* (final price:  \npending negotiation)$241.00** (final \nprice:  $230- 255)\n43 of 56https://www.cdc.gov/vaccines -for-children/php/awardees/current -cdc-vaccine -price -list.html*Updated contract price **Value used in CDC cost- effectiveness model \nPediatric Price Per Dose\nPublic Private \nMenACWYMenveo $119.986* $166.747\nMenQuadfi $114.36* $171.972\nMenBTrumenba $142.73* $207.32*\nBexsero $154.504* $237.126\nMenABCWYPenbraya $189.35 $230.75\nPenmenvy *$181.00* (final price:  \npending negotiation)$241.00** (final \nprice:  $230- 255)\n44 of 56https://www.cdc.gov/vaccines -for-children/php/awardees/current -cdc-vaccine -price -list.html*Updated contract price **Value used in CDC cost- effectiveness model \nHealth Outcomes*: Cumulative Number of IMD Cases and \nDeaths for a Single Birth Cohort from Ages 11 through 29 Years\n*All numbers are cumulative over the analytical horizon of the model for a single cohort of 11 -year -olds. For example, in the “No  Vaccination” strategy, there were a \ntotal of 233 undiscounted episodes of IMD among about 4 million individuals, who started in the model at 11 years old and age d to 29 years old.45PICO 1\nQ=Quadrivalent ( MenACWY ) vaccine; B= MenB  vaccine; P=Pentavalent ( MenABCWY ) vaccine; IMD=Invasive meningococcal disease.\n45 of 56\nCost -Effectiveness\nPICO Intervention Comparator Diff. in QALYs* Diff. in Cost*ICER\n ($/QALY)\n1 Q-P-B Q-QB-B 0 -$175 million Cost -saving**\n2 P-P Q-Q 33 $373 million $11,332,778\n3 Q-P-PQ-QB-B 2 -$166 million Cost -saving\nQ-P-B 2 $9 million $4,510,830\n*Annual discount is 3%; 2024$; **In this comparison, costs are reduced, but health outcomes remain the same when comparing Q -P-B to Q -QB-B.46\nQ=Quadrivalent ( MenACWY ) vaccine; B= MenB  vaccine; P=Pentavalent ( MenABCWY ) vaccine; QALY=Quality -adjusted life year.•In a sensitivity analysis, with the updated price assumptions, PICO \n#1 (Q -P-B) remained cost -saving (when compared to Q -QB-B).\n46 of 56\nResource Use\nIs the intervention a reasonable and efficient allocation of resources?\nNo Probably \nnoProbably \nyesYes VariesDon’t \nknow\nPICO 1 (QPB vs. QQBB):\nMenABCWY vs. MenACWY + MenBX X\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY vs. MenACWYX X\nPICO 3 (QPP vs. QQBB):  \nMenABCWY vs. MenB  X X\nPICO 1 (QPB vs. QQBB):\nMenABCWY vs. MenACWY + MenBX\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY vs. MenACWYX X\nPICO 3 (QPP vs. QQBB):  \nMenABCWY vs. MenB  X*\n*WG sentiment varied from no to yes 4747 of 56\nEvidence-to-Recommendations \nFramework\nEtR Domain QuestionWork Group \nDetermination – \nPICO 1Work Group \nDetermination – \nPICO 2Work Group \nDetermination – \nPICO 3\nPublic health \nproblemIs invasive meningococcal disease a problem of public health importance?Yes Yes Yes\nBenefits and harmsHow substantial are the desirable anticipated effects? Small Small Small\nHow substantial are the undesirable anticipated effects? Minimal Small Minimal\nDo the desirable anticipated effects outweigh the undesirable effects?Favors \nintervention/  \nfavors comparison*Favors intervention/ \ncomparison/bothFavors \nintervention/ \ncomparison/both\nWhat is the overall certainty of evidence? Low Low Low\nValues Does the target population feel the desirable effects are large relative to the undesirable effects?Yes Probably yes Probably yes/yes/\ndon’t know\nIs there important variability in how patients value the \noutcome?Probably not/no Probably/probably \nnotProbably/probably \nnot\nAcceptability Is the intervention acceptable to key stakeholders? Yes Probably yes Probably yes/yes\nResource use Is the intervention a reasonable and efficient allocation of \nresources?Yes Probably no/varies Varies\nHealth equity What would be the impact of the intervention on health equity?Probably increased Probably \nincreased/increasedProbably increased\nFeasibility Is the intervention feasible to implement? Yes Probably yes/yes Yes\n*Added since last presented to ACIP\nBalance of Consequences\nUndesirable \nconsequences \nclearly outweigh \ndesirable \nconsequences in \nmost settingsUndesirable \nconsequences \nprobably outweigh \ndesirable \nconsequences in \nmost settingsThe balance \nbetween \ndesirable and \nundesirable \nconsequences is \nclosely balanced \nor uncertainDesirable \nconsequences \nprobably \noutweigh \nundesirable \nconsequences in \nmost settingsDesirable \nconsequences \nclearly \noutweigh \nundesirable \nconsequences \nin most settingsThere is \ninsufficient \nevidence to \ndetermine the \nbalance of \nconsequences\nPICO 1 (QPB vs. QQBB):\nMenABCWY  vs. MenACWY  + MenBX\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY  vs. MenACWYX X\nPICO 3 (QPP vs. QQBB):  \nMenABCWY  vs. MenB   X X X\nPICO 1 (QPB vs. QQBB):\nMenABCWY  vs. MenACWY  + MenBX* X\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY  vs. MenACWYX X X\nPICO 3 (QPP vs. QQBB):  \nMenABCWY  vs. MenB   X X X X\n*Added since last presented to ACIP\nWork Group Interpretation\nIs there sufficient information to move forward with a recommendation?  \nYes No\nPICO 1 (QPB vs. QQBB):\nMenABCWY  vs. MenACWY  + \nMenBX\nPICO 2 (PPB vs. QQBB or PP \nvs. QQ):\nMenABCWY  vs. MenACWYX\nPICO 3 (QPP vs. QQBB):  \nMenABCWY  vs. MenB   X\n6251 of 56\nWork Group Interpretation\nWe do not \nrecommend the \ninterventionWe do \nrecommend the \nintervention\nPICO 1 (QPB vs. QQBB):\nMenABCWY  vs. MenACWY  + MenBX\nPICO 2 (PPB vs. QQBB or PP vs. QQ):\nMenABCWY  vs. MenACWYX\nPICO 3 (QPP vs. QQBB):  \nMenABCWY  vs. MenB   X X\n6352 of 56\n53Comments Regarding Proposed Recommendation\nPICO 1 would typically involve 1 dose of \npentavalent vaccine (and 1 dose of MenB vaccine)\n–Studies evaluated 2 doses of pentavalent vaccine\nRecommendations for use of both pentavalent vaccines could be revisited as part of future adolescent schedule deliberations if desired\n53 of 56\nVote Language\nACIP recommends GSK’s MenABCWY  vaccine may be used when both \nMenACWY  and MenB  are indicated at the same visit*\n*1) healthy persons aged 16 –23 years (routine schedule) when shared clinical decision-\nmaking favors administration of MenB  vaccine and 2) persons aged ≥10 years who are \nat increased risk for meningococcal disease (e.g., because of persistent complement \ndeficiencies, complement inhibitor use, or functional or anatomic asplenia) PICO 1 (QPB) √\nPICO 2 (PP) X\nPICO 3 (QPP) X\n54 of 56\n55Acknowledgements\nAvnika Amin\nLucy McNamara\nXiaoyu Dong\nAndrew Leidner\nRebecca Morgan\nDoug Campos -Outcalt\nNoele Nelson\nAlison Albert\nSusan Hariri\nLeAnne Fox\nJennifer Collins\nAmy Rubis\n61 of 6255 of 56\nThank you!\nFor more information, contact CDC\n1-800- CDC- INFO (232- 4636)\nTTY:  1 -888- 232- 6348    cdc.gov\nFollow us on X (Twitter) @CDCgov & @CDCEnvironment\nThe findings and conclusions in this report are those of the authors and do not necessarily represent the official position o f \nthe U. S. Centers for Disease Control and Prevention.", "summary": "GSK Pentavalent ( MenABCWY ) Vaccine:   Review of Updated EtR and Work Group  Considerations Sarah Schillie, MD, MPH, MBA Advisory Committee on Immunization Practices April 16, 2025National Center for Immunization & Respiratory Diseases 1 The findings and conclusions in this report are those of the authors and do not necessarily represent the official position o f  the U. S. Centers for Disease Control and Prevention. Meningococcal Vaccine Recommendations  2 of 56One MenACWY  dose at  age 11…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/02-Schillie-mening-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 56}
{"title": "03 Santoli mening 508", "content": "VFC Resolution Update:  Meningococcal Vaccines\nJeanne Santoli, MD, MPH\nApril 16, 2025National Center for Immunization & Respiratory Diseases\n\n•Orange font/highlight in the presentation is used to indicate changes to \nthe resolution in comparison to the prior approved version.Note\n•The purpose of this resolution is to update the resolution to incorporate a \nnew combination pentavalent vaccine. Purpose of the Resolution\nEligible Groups\n•  Children aged 2 months through 10 years who are at increased risk for meningococcal \ndisease attributable to serogroups A, C, W, and Y, including:\n-Children who have persistent complement component deficiencies (including inherited or \nchronic deficiencies in C3, C5 -C9, properdin, factor H, or factor D)\n-Children taking a complement inhibitor (e.g., eculizumab [Soliris], ravulizumab [Ultomiris ])\n-Children who have anatomic or functional asplenia, including sickle cell disease\n-Children infected with human immunodeficiency virus (HIV)\n-Children traveling to or residing in countries in which meningococcal disease is hyperendemic or epidemic, particularly if contact with local population will be prolonged \n-Children identified to be at increased risk because of a meningococcal disease outbreak \nattributable to serogroups A, C, W, or Y\n•  All children aged 11 through 18 yearsMeningococcal Conjugate Vaccines ( MenACWY)\nRecommended Vaccination Schedule and Intervals\n•The table below lists meningococcal conjugate vaccines currently available to prevent \nmeningococcal disease attributable to serogroups A, C, W, and Y. Meningococcal Conjugate Vaccines ( MenACWY)\nVaccine Type Brand\n(1)Age \nindication \n(pediatric)Children at increased riskChildren not at \nincreased risk\n2m through 23m 2ythrough 18y Booster Doses\nPrimary:  1 dose \nat age 11 -12y \n(or 13y  -18y) if \nnot vaccinated \npreviously\nBooster:  1 dose \nat age 16y (if \nvaccinated at \n11y  -12y) or 1 \ndose at 16y -\n18y (if \nvaccinated at \n13y -15y)Men-ACWY -\nCRM \n(lyophilized)Menveo \nTwo-Vial  2m –18y Initiating at 2m : 4 \ndoses, at 2, 4, 6, and 12m\nInitiating at 7 -\n23m:  2 doses, 12 \nwksapartFor children with persistent complement deficiencies, \ncomplement \ninhibitor use (2), functional or anatomic asplenia, or \nHIV: 2 doses, \n≥8 wksapart\nOther children \nat increased \nrisk: 1 doseFor children who \nremain at increased \nri sk and compl eted \nthe primary dose or \nseries at age:\n< 7y:  ad d itional d ose \n3 years after primary; \nboosters should be \nrepeated every 5 \nyears\n>7y:  ad d itional d ose \n5 yrs after primary; \nboosters should be \nrepeated every 5 \nyearsMen-ACWY -\nCRM (liquid)M enveo One-Via l10y –18y Not ind icated\nMen-ACWY -TT M enQuadfi 2y –18y Not ind icated\nTable Notes\n(1) Use of brand names is not meant to preclude the use of other comparable US licensed \nvaccines\n(2) Includes eculizumab (Soliris) and ravulizumab (Ultomiris )\nRecommended schedules and intervals for meningococcal conjugate vaccines can be found at  \nMeningococcal Vaccination: Recommendations of the Advisory Committee on Immunization \nPractices, United States, 2020 | MMWR\nRecommended dosage Refer to product package inserts.\nContraindications and Precautions\nContraindications and Precautions can be found in the package inserts available at Vaccines \nLicensed for Use in the United States | FDAMeningococcal Conjugate Vaccines ( MenACWY)\nEligible Groups\n•  Children aged 10 through 18 years at increased risk for serogroup B meningococcal \ndisease, including: \n-Children who have persistent complement component deficiencies (including inherited or \nchronic deficiencies in C3, C5 -C9, properdin, factor H, or factor D)\n-Children taking a complement inhibitor (e.g., eculizumab [Soliris], ravulizumab [Ultomiris ]) \n-Children who have anatomic or functional asplenia, including sickle cell disease\n-Children identified to be at increased risk because of a meningococcal disease outbreak \nattributable to serogroup B\n•  Children aged 16 through 18 years who are not at increased risk for serogroup B \nmeningococcal disease may also be vaccinated when shared clinical decision -making \nfavors administration of MenB . Serogroup B Meningococcal Vaccines ( MenB )\nRecommended Vaccination Schedule and IntervalsSerogroup B Meningococcal Vaccines ( MenB )\nVaccine (1), (3) Age Group Dosing Schedule (Primary \nSeries)Dosing Schedule (Booster Dose)\nMenB -4C \n(Bexsero, GSK)\nMenB -FHbp\n(Trumenba , Pfizer)10y -18y -Persons at increased risk \nfor meningococcal disease \nincluding during \nserogroup B outbreaks: \nThree doses (0, 1 -2, and 6 \nmonth schedule)\n-Adolescents who are not \nat increased risk for \nmeningococcal disease: Two doses (0, 6 month schedule) (2)-For children at increased risk due to \ncomplement deficiency, complement inhibitor \nuse, or functional or anatomic asplenia: \nA booster dose is recommended if it has been a  \nleast one year since primary series; repeat every \n2-3 years as long as risk remains.\n-For children at increased risk due to a \nserogroup B outbreak:\nA booster dose is recommended if it has been a  \nleast one year since primary series. If recommended by public health officials, \nbooster dose may be given if it has been at leas  \n6 months since primary series.  \n-Booster doses are not recommended for \nadolescents who are not at increased risk for \nmeningococcal disease.\nTable Notes\n(1)  Use of brand names is not meant to preclude the use of other comparable US licensed vaccines. \n(2)  If the second dose is administered earlier than 6 months after the first dose, a third dose should \nbe administered at least 4 months after the second dose.  \n(3)  MenB vaccines are not interchangeable by manufacturer. Administration of a B component \nvaccine ( MenB or MenACWY -TT/MenB -FHbp or MenACWY -CRM/MenB -4C) requires that \nsubsequent B component vaccine doses be from the same manufacturer.\nRecommended dosage Refer to product package inserts. \nContraindications and Precautions\nContraindications and Precautions can be found in the package inserts available at Vaccines \nLicensed for Use in the United States | FDASerogroup B Meningococcal Vaccines ( MenB )\nEligible Groups\nChildren who are indicated to receive MenACWY and MenB vaccines, including: \n•Children aged 10 through 18 years who are at increased risk for meningococcal \ndisease attributable to serogroups A, C, W, Y , and B, including:\n-Children who have persistent complement component deficiencies (including \ninherited or chronic deficiencies in C3, C5 -C9, properdin, factor H, or factor D)\n-Children taking a complement inhibitor (e.g., eculizumab [Soliris], ravulizumab\n[Ultomiris ])\n-Children who have anatomic or functional asplenia, including sickle cell disease\n•Children aged 16 through 18 years for whom both MenACWY and MenB are \nindicated to be given at the same time and shared clinical decision -making favors \nadministration of MenB vaccine.Combination Pentavalent Serogroup A, C, W, Y , and B \nMeningococcal Vaccines ( MenACWY -MenB )\nThe table below displays dosing schedules for the combination pentavalent vaccines\nMenACWY -TT/MenB -FHbp (Penbraya ) and MenACWY -CRM/MenB -4C (Penmenvy) (1).Combination Pentavalent Serogroup A, C, W, Y , and B \nMeningococcal Vaccines ( MenACWY -MenB )\nChildren at Increased Risk (10y through 18y)\nChildren not at Increased RiskDosing Schedule \n(Primary Series) Dosing Schedule (Boosters)\nFor children with persistent complement \ndeficiencies, complement inhibitor use (2), \nor functional or anatomic asplenia who are \ndue for both MenACWY and MenB\nvaccination: 1 dose may be given in lieu of \nMenACWY and MenB . \nIf subsequent doses of MenACWY and/or \nMenB (3) are indicated less than 6 months \nafter a dose of combination pentavalent \nvaccine ,  the vaccines should be given \nseparately according to the MenACWY and \nMenB tables above. For subsequent doses, where both MenACWY and MenB are \nindicated and at least 6 months \nhave passed since administration of a previous dose of combination pentavalent vaccine, a second \ndose of combination pentavalent vaccine from the same manufacturer may be \nused (3). Initial dose: \nMay be given in lieu of MenACWY and MenB when \nboth vaccines are indicated at the same visit (e.g., age 16 years) and shared clinical decision -making \nfavors administration of MenB .\nSecond dose: The MenB series should then be completed with a\nMenB component from the same manufacturer (3).  \nTable Notes\n(1) Use of brand names is not meant to preclude the use of other comparable US licensed vaccines.\n(2) Includes eculizumab (Soliris) and ravulizumab (Ultomiris ).\n(3) MenB vaccines are not interchangeable by manufacturer. Administration of a B component \nvaccine ( MenB , MenACWY -TT/MenB -FHbp , or MenACWY -CRM/MenB -4C ) requires that subsequent \nB component vaccine doses be from the same manufacturer.\nRecommended dosage Refer to product package inserts. \nContraindications and Precautions\nContraindications and Precautions can be found in the package inserts available at Vaccines Licensed \nfor Use in the United States | FDACombination Pentavalent Serogroup A, C, W, Y , and B \nMeningococcal Vaccines ( MenACWY- MenB )\n•[If an ACIP recommendation or notice regarding meningococcal vaccination is \npublished within 6 months following this resolution, the relevant language above (except in the eligible groups sections) will be replaced with the language in the \nrecommendation and incorporated by reference to the publication URL.]Statement Regarding Update Based on Published  Documents", "summary": "VFC Resolution Update:  Meningococcal Vaccines Jeanne Santoli, MD, MPH April 16, 2025National Center for Immunization & Respiratory Diseases  •Orange font/highlight in the presentation is used to indicate changes to  the resolution in comparison to the prior approved version.Note •The purpose of this resolution is to update the resolution to incorporate a  new combination pentavalent vaccine. Purpose of the Resolution Eligible Groups •  Children aged 2 months through 10 years who are at…", "source_url": "https://www.cdc.gov/acip/meetings/presentation-slides-april-15-16-2025.html", "pdf_url": "https://www.cdc.gov/acip/downloads/slides-2025-04-15-16/03-Santoli-mening-508.pdf", "doc_date": "2025-04-15", "case": "acip", "sub_case": "slides", "tags": ["acip", "cdc", "vaccines", "slides"], "page_count": 13}